PMID- 18706911
TI  - GAPDH is conformationally and functionally altered in association with oxidative
      stress in mouse models of amyotrophic lateral sclerosis.
AB  - It is proposed that conformational changes induced in proteins by oxidation can
      lead to loss of activity or protein aggregation through exposure of hydrophobic
      residues and alteration in surface hydrophobicity. Because increased oxidative
      stress and protein aggregation are consistently observed in amyotrophic lateral
      sclerosis (ALS), we used a 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid
      (BisANS) photolabeling approach to monitor changes in protein unfolding in vivo
      in skeletal muscle proteins in ALS mice. We find two major proteins, creatine
      kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH),
      conformationally affected in the ALS G93A mouse model concordant with a 43% and
      41% reduction in enzyme activity, respectively. This correlated with changes in
      conformation and activity that were detected in CK and GAPDH with in vitro
      oxidation. Interestingly, we found that GAPDH, but not CK, is conformationally
      and functionally affected in a longer-lived ALS model (H46R/H48Q), exhibiting a
      22% reduction in enzyme activity. We proposed a reaction mechanism for BisANS
      with nucleophilic amino acids such as lysine, serine, threonine, and tyrosine,
      and BisANS was found to be primarily incorporated to lysine residues in GAPDH. We
      identified the specific BisANS incorporation sites on GAPDH in nontransgenic
      (NTg), G93A, and H46R/H48Q mice using liquid chromatography-tandem mass
      spectrometry analysis. Four BisANS-containing sites (K52, K104, K212, and K248)
      were found in NTg GAPDH, while three out of four of these sites were lost in
      either G93A or H46R/H48Q GAPDH. Conversely, eight new sites (K2, K63, K69, K114,
      K183, K251, S330, and K331) were found on GAPDH for G93A, including one common
      site (K114) for H46R/H48Q, which is not found on GAPDH from NTg mice. These data
      show that GAPDH is differentially affected structurally and functionally in vivo
      in accordance with the degree of oxidative stress associated with these two
      models of ALS.

PMID- 18706912
TI  - Crystal structure of the Ig1 domain of the neural cell adhesion molecule NCAM2
      displays domain swapping.
AB  - The crystal structure of the first immunoglobulin (Ig1) domain of neural cell
      adhesion molecule 2 (NCAM2/OCAM/RNCAM) is presented at a resolution of 2.7 A.
      NCAM2 is a member of the immunoglobulin superfamily of cell adhesion molecules
      (IgCAMs). In the structure, two Ig domains interact by domain swapping, as the
      two N-terminal beta-strands are interchanged. beta-Strand swapping at the
      terminal domain is the accepted mechanism of homophilic interactions amongst the
      cadherins, another class of CAMs, but it has not been observed within the IgCAM
      superfamily. Gel-filtration chromatography demonstrated the ability of NCAM2 Ig1
      to form dimers in solution. Taken together, these observations suggest that beta
      strand swapping could have a role in the molecular mechanism of homophilic
      binding for NCAM2.

PMID- 18706913
TI  - Competitive Lrp and Dam assembly at the pap regulatory region: implications for
      mechanisms of epigenetic regulation.
AB  - Escherichia coli DNA adenine methyltransferase (Dam) and Leucine-responsive
      regulatory protein (Lrp) are key regulators of the pap operon, which codes for
      the pilus proteins necessary for uropathogenic E. coli cellular adhesion. The pap
      operon is regulated by a phase variation mechanism in which the methylation
      states of two GATC sites in the pap regulatory region and the binding position of
      Lrp determine whether the pilus genes are expressed. The post-replicative
      reassembly of Dam, Lrp, and the local regulator PapI onto a hemimethylated pap
      intermediate is a critical step of the phase variation switching mechanism and is
      not well understood. We show that Lrp, in the presence and in the absence of PapI
      and nonspecific DNA, specifically protects pap regulatory GATC sites from Dam
      methylation when allowed to compete with Dam for assembly on unmethylated and
      hemimethylated pap DNA. The methylation protection is dependent upon the
      concentration of Lrp and does not occur with non-regulatory GATC sites. Our data
      suggest that only at low Lrp concentrations will Dam compete effectively for
      binding and methylation of the proximal GATC site, leading to a phase switch
      resulting in the expression of pili.

PMID- 18706914
TI  - Identification of a dimeric intermediate in the unfolding pathway for the calcium
      binding protein S100B.
AB  - The S100 proteins comprise 25 calcium-signalling members of the EF-hand protein
      family. Unlike typical EF-hand signalling proteins such as calmodulin and
      troponin-C, the S100 proteins are dimeric, forming both homo- and heterodimers in
      vivo. One member of this family, S100B, is a homodimeric protein shown to control
      the assembly of several cytoskeletal proteins and regulate phosphorylation events
      in a calcium-sensitive manner. Calcium binding to S100B causes a conformational
      change involving movement of helix III in the second calcium-binding site (EF2)
      that exposes a hydrophobic surface enabling interactions with other proteins such
      as tubulin and Ndr kinase. In several S100 proteins, calcium binding also
      stabilizes dimerization compared to the calcium-free states. In this work, we
      have examined the guanidine hydrochloride (GuHCl)-induced unfolding of dimeric
      calcium-free S100B. A series of tryptophan substitutions near the dimer interface
      and the EF2 calcium-binding site were studied by fluorescence spectroscopy and
      showed biphasic unfolding curves. The presence of a plateau near 1.5 M GuHCl
      showed the presence of an intermediate that had a greater exposed hydrophobic
      surface area compared to the native dimer based on increased 4,4-dianilino-1,1'
      binaphthyl-5,5'-disulfonic acid fluorescence. Furthermore, (1)H-(15)N
      heteronuclear single quantum coherence analyses as a function of GuHCl showed
      significant chemical shift changes in regions near the EF1 calcium-binding loop
      and between the linker and C-terminus of helix IV. Together these observations
      show that calcium-free S100B unfolds via a dimeric intermediate.

PMID- 18706915
TI  - Cryo-electron microscopy structure of a yeast mitochondrial preprotein
      translocase.
AB  - The translocase of the outer mitochondrial membrane (TOM) complex is the main
      entry gate for proteins imported into mitochondria. We determined the structure
      of the native, unstained approximately 550-kDa core-Tom20 complex from
      Saccharomycescerevisiae by cryo-electron microscopy at 18-A resolution. The
      complex is triangular, measuring 145 A on edge, and has near-3-fold symmetry. Its
      bulk is made up of three globular approximately 50-A domains. Three elliptical
      pores on the c-face merge into one central approximately 70-A cavity with a cage
      like assembly on the opposite t-face. Nitrilotriacetic acid-gold labeling
      indicates that three Tom22 subunits in the TOM complex are located at the
      perimeter of the complex near the interface of the globular domains. We assign
      Tom22, which controls complex assembly, to three peripheral protrusions on the c
      face, while the Tom20 subunit is tentatively assigned to the central protrusion
      on this surface. Based on our three-dimensional map, we propose a model of
      transient interactions and functional dynamics of the TOM assembly.

PMID- 18706916
TI  - Efficient selection of DARPins with sub-nanomolar affinities using SRP phage
      display.
AB  - There is an ever-increasing demand to select specific, high-affinity binding
      molecules against targets of biomedical interest. The success of such selections
      depends strongly on the design and functional diversity of the library of binding
      molecules employed, and on the performance of the selection strategy. We recently
      developed SRP phage display that employs the cotranslational signal recognition
      particle (SRP) pathway for the translocation of proteins to the periplasm. This
      system allows efficient filamentous phage display of highly stable and fast
      folding proteins, such as designed ankyrin repeat proteins (DARPins) that are
      virtually refractory to conventional phage display employing the post
      translational Sec pathway. DARPins comprise a novel class of binding molecules
      suitable to complement or even replace antibodies in many biotechnological or
      biomedical applications. So far, all DARPins have been selected by ribosome
      display. Here, we harnessed SRP phage display to generate a phage DARPin library
      containing more than 10(10) individual members. We were able to select well
      behaved and highly specific DARPins against a broad range of target proteins
      having affinities as low as 100 pM directly from this library, without affinity
      maturation. We describe efficient selection on the Fc domain of human IgG,
      TNFalpha, ErbB1 (EGFR), ErbB2 (HER2) and ErbB4 (HER4) as examples. Thus, SRP
      phage display makes filamentous phage display accessible for DARPins, allowing,
      for example, selection under harsh conditions or on whole cells. We envision that
      the use of SRP phage display will be beneficial for other libraries of stable and
      fast-folding proteins.

PMID- 18706917
TI  - The control of vector-borne disease epidemics.
AB  - The theoretical underpinning of our struggle with vector-borne disease, and still
      our strongest tool, remains the basic reproduction number, R(0), the measure of
      long term endemicity. Despite its widespread application, R(0) does not address
      the dynamics of epidemics in a model that has an endemic equilibrium. We use the
      concept of reactivity to derive a threshold index for epidemicity, E(0), which
      gives the maximum number of new infections produced by an infective individual at
      a disease free equilibrium. This index describes the transitory behavior of
      disease following a temporary perturbation in prevalence. We demonstrate that if
      the threshold for epidemicity is surpassed, then an epidemic peak can occur, that
      is, prevalence can increase further, even when the disease is not endemic and so
      dies out. The relative influence of parameters on E(0) and R(0) may differ and
      lead to different strategies for control. We apply this new threshold index for
      epidemicity to models of vector-borne disease because these models have a long
      history of mathematical analysis and application. We find that both the
      transmission efficiency from hosts to vectors and the vector-host ratio may have
      a stronger effect on epidemicity than endemicity. The duration of the extrinsic
      incubation period required by the pathogen to transform an infected vector to an
      infectious vector, however, may have a stronger effect on endemicity than
      epidemicity. We use the index E(0) to examine how vector behavior affects
      epidemicity. We find that parasite modified behavior, feeding bias by vectors for
      infected hosts, and heterogeneous host attractiveness contribute significantly to
      transitory epidemics. We anticipate that the epidemicity index will lead to a
      reevaluation of control strategies for vector-borne disease and be applicable to
      other disease transmission models.

PMID- 18706918
TI  - Augmented sparse reconstruction of protein signaling networks.
AB  - The problem of reconstructing and identifying intracellular protein signaling and
      biochemical networks is of critical importance in biology. We propose a
      mathematical approach called augmented sparse reconstruction for the
      identification of links among nodes of ordinary differential equation (ODE)
      networks, given a small set of observed trajectories with various initial
      conditions. As a test case, the method is applied to the epidermal growth factor
      receptor (EGFR) driven signaling cascade, a well-studied and clinically important
      signaling network. Our method builds a system of representation from a collection
      of trajectory integrals, selectively attenuating blocks of terms in the
      representation. The system of representation is then augmented with random
      vectors, and l(1) minimization is used to find sparse representations for the
      dynamical interactions of each node. After showing the performance of our method
      on a model of the EGFR protein network, we sketch briefly the potential future
      therapeutic applications of this approach.

PMID- 18706919
TI  - Seasonal and altitudinal effects on glucocorticoid metabolites in a wild primate
      (Theropithecus gelada).
AB  - Behavioral ecologists are increasingly adopting sophisticated non-invasive
      methods for measuring glucocorticoids from "excreta" because samples are easy to
      collect, animals are left undisturbed, and measures may be more reflective of
      external events than serum samples. Some of the most common predictors for
      hormone profiles in wild animals are seasonal changes in ecology and behavior.
      For example, we might expect baseline glucocorticoid levels to track changes in
      food availability or other seasonal stressors such as unusually high or low
      temperatures. Geladas (Theropithecus gelada) are one of the few non-human
      primates that live at extremely high altitudes where nighttime temperatures often
      dip below freezing. However, the physiological effects of this relatively
      inhospitable environment have never been examined in this species. Here we
      validate a "field-friendly" method of hormone extraction from gelada feces and
      demonstrate that this method can be used to detect seasonal and altitudinal
      differences in glucocorticoid metabolites for this species. We use two years of
      climatological and hormonal data from a wild population of geladas to test the
      hypothesis that geladas exhibit elevated glucocorticoids under environmentally
      "challenging" conditions - mainly, when temperatures and rainfall are low and
      altitude is high. Our results indicate that cold temperatures and high altitude
      predicted elevated glucocorticoids, but low rainfall did not. Therefore, we
      suggest a metabolic hypothesis (as opposed to a nutritional hypothesis) to
      explain this result. However, at the present time, we cannot rule out a
      behavioral stress hypothesis.

PMID- 18706920
TI  - Tissue distribution and urinary excretion of inorganic arsenic and its methylated
      metabolites in C57BL6 mice following subchronic exposure to arsenate in drinking
      water.
AB  - The relationship of exposure and tissue concentration of parent chemical and
      metabolites over prolonged exposure is a critical issue for chronic toxicities
      mediated by metabolite(s) rather than parent chemical alone. This is an issue for
      AsV because its trivalent metabolites have unique toxicities and relatively
      greater potency compared to their pentavalent counterparts for many endpoints. In
      this study, dose-dependency in tissue distribution and urinary excretion for
      inorganic arsenic and its methylated metabolites was assessed in female C57Bl/6
      mice exposed to 0, 0.5, 2, 10 or 50 ppm arsenic (as arsenate, AsV) in their
      drinking water for 12 weeks. No adverse effects were observed and body weight
      gain did not differ significantly among groups. Urinary excretion of arsenite
      monomethylarsonous acid (MMA(III)), dimethylarsinous acid (DMA(III)),
      dimethylarsinic acid (DMAV), and trimethylarsine oxide (TMAO) increased linearly
      with dose, whereas AsV and monomethylarsonic acid (MMAV) excretion was non-linear
      with respect to dose. Total tissue arsenic accumulation was greatest in kidney >
      lung > urinary bladder >>> skin > blood > liver. Monomethyl arsenic (MMA, i.e.
      MMA(III)+MMAV) was the predominant metabolite in kidney, whereas dimethylarsenic
      (DMA, i.e., DMA(III)+DMAV) was the predominant metabolite in lung. Urinary
      bladder tissue had roughly equivalent levels of inorganic arsenic and
      dimethylarsenic, as did skin. These data indicate that pharmacokinetic models for
      arsenic metabolism and disposition need to include mechanisms for organ-specific
      accumulation of some arsenicals and that urinary metabolite profiles are not
      necessarily reflective of target tissue dosimetry.

PMID- 18706921
TI  - Inhalation of the nerve gas sarin impairs ventilatory responses to hypercapnia
      and hypoxia in rats.
AB  - Sarin, a highly toxic nerve gas, is believed to cause bronchoconstriction and
      even death primarily through respiratory failure; however, the mechanism
      underlying the respiratory failure is not fully understood. The goals of this
      study were to ascertain whether sarin affects baseline ventilation (VE) and VE
      chemoreflexes as well as airway resistance and, if so, whether these changes are
      reversible. Four groups of F344 rats were exposed to vehicle (VEH) or sarin at
      2.5, 3.5, and 4.0 mg h m(-3) (SL, SM, and SH, respectively). VE and VE responses
      to hypercapnia (7% CO2) or hypoxia (10% O2) were measured by plethysmography at 2
      h and 1, 2, and 5 days after VEH or sarin exposure. Total pulmonary resistance
      (RL) also was measured in anesthetized VEH- and SH-exposed animals 2 h after
      exposure. Our results showed that within 2 h after exposure 11% of the SM- and
      52% of the SH- exposed groups died. Although the SM and SH significantly
      decreased hypercapnic and hypoxic VE to similar levels (64 and 69%), SH induced
      greater respiratory impairment, characterized by lower baseline VE (30%; P<0.05),
      and total loss of the respiratory frequency response to hypercapnia and hypoxia.
      VE impairment recovered within 1-2 days after sarin exposure; interestingly, SH
      did not significantly affect baseline RL. Moreover, sarin induced body tremors
      that were unrelated to the changes in the VE responses. Thus, LC50 sarin causes a
      reversible impairment of VE that is not dependent on the sarin-induced body
      tremors and not associated with changes in RL.

PMID- 18706922
TI  - Profiling of benzophenone derivatives using fish and human estrogen receptor
      specific in vitro bioassays.
AB  - Benzophenone (BP) derivatives, BP1 (2,4-dihydroxybenzophenone), BP2 (2,2',4,4'
      tetrahydroxybenzophenone), BP3 (2-hydroxy-4-methoxybenzophenone), and THB (2,4,4'
      trihydroxybenzophenone) are UV-absorbing chemicals widely used in pharmaceutical,
      cosmetics, and industrial applications, such as topical sunscreens in lotions and
      hair sprays to protect skin and hair from UV irradiation. Studies on their
      endocrine disrupting properties have mostly focused on their interaction with
      human estrogen receptor alpha (hERalpha), and there has been no comprehensive
      analysis of their potency in a system allowing comparison between hERalpha and
      hERbeta activities. The objective of this study was to provide a comprehensive ER
      activation profile of BP derivatives using ER from human and fish origin in a
      battery of in vitro tests, i.e., competitive binding, reporter gene based assays,
      vitellogenin (Vtg) induction in isolated rainbow trout hepatocytes, and
      proliferation based assays. The ability to induce human androgen receptor (hAR)
      mediated reporter gene expression was also examined. All BP derivatives tested
      except BP3 were full hERalpha and hERbeta agonists (BP2>THB>BP1) and displayed a
      stronger activation of hERbeta compared with hERalpha, the opposite effect to
      that of estradiol (E2). Unlike E2, BPs were more active in rainbow trout ERalpha
      (rtERalpha) than in hERalpha assay. All four BP derivatives showed anti
      androgenic activity (THB>BP2>BP1>BP3). Overall, the observed anti-androgenic
      potencies of BP derivatives, together with their proposed greater effect on
      ERbeta versus ERalpha activation, support further investigation of their role as
      endocrine disrupters in humans and wildlife.

PMID- 18706923
TI  - Epidemiologic and clinical survey of victims of centipede stings admitted to
      Hospital Vital Brazil (Sao Paulo, Brazil).
AB  - We retrospectively analyzed 98 proven cases of centipede stings admitted to
      Hospital Vital Brazil, Butantan Institute, Sao Paulo, Brazil, between 1990 and
      2007. Most stings occurred at the metropolitan area of Sao Paulo city (n=94,
      95.9%), in the domiciles of patients (n=67, 68.4%), and during the warm-rainy
      season (n=60, 61.2%). The mean age of the victims was 32.0+/-18.8-years-old.
      Cryptops and Otostigmus genera were responsible for most cases. Around 86% of the
      patients sought medical care within 6h after the sting. Both lower (56.1 %) and
      upper limbs (41.8 %) were most frequently bitten, especially the feet and hands
      (89.8%). The most frequent local clinical manifestations were pain (94.9%),
      erythema (44.9%) and edema (21.4%), and the latter was mainly observed in
      patients bitten by Otostigmus spp. Supportive treatment was used in only 28.6% of
      the patients, namely administration of local anesthesia (9.2%) and systemic
      analgesia (13.3%). No sequels or complications were observed in patients, and the
      prognostic was benign.

PMID- 18706924
TI  - The extracellular proteoglycan produced by Rhodella grisea.
AB  - Highly viscous extracellular proteoglycan (EPG) has been isolated from culture
      medium of the unicellular red alga Rhodella grisea (Rhodophyceae) by ethanol
      precipitation. EPG was composed of xylose (29.3%), 3-O-methyl-xylose (26.0%),
      uronic acids (17.1%), rhamnose (14.4%), galactose (7.5%), glucose (3.9%),
      arabinose (1.4%) and mannose (0.4%), and traces of fucose, 4-O-methyl-xylose and
      2,3-di-O-methyl-rhamnose or fucose. In addition, the polymer contained proteins
      (13.1%), sulphates and 13C-CP MAS spectra indicated the presence of acetyl and
      succinyl groups. The molecular mass was estimated to be 136,000. Ion-exchange
      chromatography afforded five fractions differing in composition of neutral
      sugars, uronic acids, and protein content indicating thus the complex structure
      of the EPG.

PMID- 18706925
TI  - An extracellular galactoxylomannan of acapsular Cryptococcus laurentii mutant.
AB  - An extracellular galactoxylomannan (GalXM) composed of D-Gal (34.0%), D-Xyl
      (26.6%) and D-Man (31.0%), and a small amount of L-Ara (4.0%) and D-Glc (4.4%)
      has been isolated from culture medium of acapsulated mutant of Cryptococcus
      laurentii by ethanol precipitation and gel filtration. Phosphorylated polymer of
      Mw approximately 75,000 contained 90% carbohydrates, 3.9% phosphorus and 5.3%
      proteins. Results of chemical and spectroscopic studies showed a highly branched
      structure of GalXM with a 1,6-linked mannopyranosyl-galactopyranosyl backbone
      (approximately 44%) branched predominantly at C-2 and C-3 of mannosyl, and C-3 of
      galactosyl residues by side chains terminated mainly by xylosyl and mannosyl
      residues, and to a less extent by arabinosyl and glucosyl ones.

PMID- 18706927
TI  - 3,4-Dihydroxyphenylacetic acid (DOPAC) modulates the toxicity induced by nitric
      oxide in PC-12 cells via mitochondrial dysfunctioning.
AB  - It has been postulated that dihydroxyphenylacetic acid (DOPAC), a major dopamine
      metabolite, and nitric oxide (NO) induce mitochondrial dysfunction in a
      synergistic manner. We examined the combined effects of NO and DOPAC on PC-12
      cells in terms of cell viability, nuclear morphology, mitochondrial parameters
      and cell death mechanisms. The apoptotic cell death induced by the NO-donor, S
      nitroso-N-acetylpenicillamine (SNAP), was differently modulated by DOPAC as a
      function of DOPAC/cell ratios. Whereas below 200nmol/10(6) cells, DOPAC inhibited
      a typical apoptotic pathway induced by exposure the cells to the NO donor, above
      200nmol DOPAC/10(6) cells, the cell death was not only enhanced but encompassed a
      distinct mechanism. Loading the cells with dopamine mimicked the effects of
      DOPAC. Specifically, the combination of DOPAC and NO induced an early
      mitochondrial membrane potential dissipation and ATP depletion followed by loss
      of cellular membrane integrity. Mitochondrial dysfunction was accompanied by the
      release of cytochrome c in both cases, NO individually and in combination with
      DOPAC, but caspase-3 and caspase-9 activation were only observed in the absence
      of DOPAC. DOPAC alone was ineffective. Thus, our results suggest a role for DOPAC
      as a modulator of cell fate and point to a pathway of cell death involving DOPAC
      and NO, via mechanisms that include mitochondrial dysfunction but do not involve
      the activation of the typical apoptotic caspase cascade. The significance of
      these results is discussed in connection with the mechanisms of cell death
      underlying Parkinson's disease.

PMID- 18706926
TI  - Cardiovascular functioning, personality, and the social world: the domain of
      hierarchical power.
AB  - The present paper considers connections between cardiovascular functioning (i.e.,
      disease status and acute stress responses) and social dominance, and its
      counterpart, social submissiveness, both of which are part of the broader domain
      of "hierarchical power" [Bugental, D.B., 2000. Acquisition of the algorithms of
      social life: a domain-based approach. Psychological Bulletin 126, 187-219].
      Empirical research on connections between dominance/submissiveness and
      cardiovascular morbidity and mortality in humans is reviewed, as is research on
      dominance/submissiveness and cardiovascular reactivity to, and recovery from,
      acute stressors. Three general conclusions are established. First, in both cross
      sectional and longitudinal investigations, trait and behavioral indicators of
      dominance have been positively associated with cardiovascular disease severity,
      incidence, and progression, whereas preliminary evidence from two studies
      suggests that trait submissiveness may protect against poorer disease outcomes.
      Second, among men and women, trait dominance is associated with reactivity to and
      recovery from acute stressors, particularly social challenges. Third, linkages
      between dominance/submissiveness and cardiovascular functioning, especially
      cardiovascular reactivity, are characterized by gender-specific patterning, and
      this patterning emerges as a function of social context. Implications for the
      next generation of research concerning social dominance, gender, and
      cardiovascular functioning are discussed.

PMID- 18706928
TI  - A flexible software tool for temporally-precise behavioral control in Matlab.
AB  - Systems and cognitive neuroscience depend on carefully designed and precisely
      implemented behavioral tasks to elicit the neural phenomena of interest. To
      facilitate this process, we have developed a software system that allows for the
      straightforward coding and temporally-reliable execution of these tasks in
      Matlab. We find that, in most cases, millisecond accuracy is attainable, and
      those instances in which it is not are usually related to predictable, programmed
      events. In this report, we describe the design of our system, benchmark its
      performance in a real-world setting, and describe some key features.

PMID- 18706929
TI  - Consensus RT-nested PCR detection of yellow head complex genotypes in penaeid
      shrimp.
AB  - A consensus RT-nested (n)PCR is described that detects the six distinct genotypic
      variants in the yellow head virus (YHV) complex. The PCR primers targeted ORF1b
      gene regions more highly conserved amongst the reference strains of YHV (genotype
      1) and gill-associated virus (GAV, genotype 2) and a set of 57 field isolates
      containing multiple representatives of each genotype. The test employed short PCR
      (359 bp) and nPCR (147 bp) amplicons to minimise the effects of RNA degradation.
      To ensure < or = 8-primer degeneracy, two primers were designed to each site, one
      accommodating sequence variations amongst genotype 1 isolates and the other
      variations amongst isolates of the other genotypes. The analytical sensitivity
      limits of the PCR and nPCR were estimated to be approximately 1250 and
      approximately 1.25 RNA copies, respectively. The superior group-specificity of
      the consensus RT-nPCR compared to other OIE-recommended PCR tests for YHV/GAV was
      demonstrated using RNA from 17 Penaeus monodon shrimp infected with
      representatives of each of the six genotypes. Phylogenetic analysis using the 94
      nt ORF1b gene sequence spanned by the nPCR primers generated genotype assignments
      that were consistent with those obtained using the extended 671 nt sequence used
      for the initial identification of genotypes.

PMID- 18706930
TI  - Development of a Taqman RT-PCR assay for the detection and quantification of
      negatively stranded RNA of human enteroviruses: evidence for false-priming and
      improvement by tagged RT-PCR.
AB  - Human enteroviruses are among the most common viruses infecting humans. These
      viruses are known to be able to infect a wide range of tissues and are believed
      to establish persistent infections. Enteroviruses are positive-sense single
      stranded RNA viruses whose replication involves the synthesis of negative strand
      intermediates. Therefore, the specific detection of negatively stranded viral RNA
      in tissues or cells is a reliable marker of active enteroviral replication. The
      present report presents the development of a real-time RT-PCR allowing the
      specific detection and quantification of negatively stranded viral RNA. Since it
      was known that specific amplification of single-stranded RNA can be made
      difficult by false-priming events leading to false-positive or overestimated
      results, the assay was developed by using a tagged RT primer. This tagged RT-PCR
      was shown to be able to amplify specifically negative RNA of enteroviruses grown
      in cell cultures by preventing the amplification of cDNAs generated by false
      priming.

PMID- 18706931
TI  - Reverse transcription loop-mediated isothermal amplification for the detection of
      highly pathogenic porcine reproductive and respiratory syndrome virus.
AB  - A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay
      targeting the open reading frames 1a of highly pathogenic porcine reproductive
      and respiratory syndrome virus genome was developed. The 10 reference strains, 1
      clinical isolation strain and 122 positive samples were tested. Positive
      reactions were confirmed for all strains and specimens by reverse transcription
      loop-mediated isothermal amplification and nested reverse transcription
      polymerase chain reaction (RT-PCR). The results showed this detection technique
      is more reliable and convenient for rapid and sensitive diagnosis of highly
      pathogenic porcine reproductive and respiratory syndrome virus infection.

PMID- 18706932
TI  - A genotypic assay for the amplification and sequencing of integrase from diverse
      HIV-1 group M subtypes.
AB  - Recently, the Food and Drug Administration (FDA) of the USA approved the first
      integrase inhibitor for inclusion in treatment regimens of HIV-1 patients failing
      their current regimens with multi-drug resistant strains. However, treatment
      failure has been observed during integrase inhibitor-containing therapy. Several
      mutational pathways have been described with signature mutations at integrase
      positions 66, 92, 148 and 155. Therefore, a genotypic assay for the amplification
      and sequencing of HIV-1 integrase was developed. The assay displayed a detection
      limit of 10 HIV-1 III(B) RNA copies/ml plasma. As the HIV-1 pandemic is
      characterised by a large genetic diversity, the new assay was evaluated on a
      panel of 74 genetically divergent samples belonging to the following genetic
      forms A, B, C, D, F, G, J, CRF01-AE, CRF02-AG, CRFF03-AB, CRF12-BF and CRF13-cpx.
      Their viral load ranged from 178 until >500,000 RNA copies/ml. The amplification
      and sequencing was successful for 70 samples (a success rate of 95%). The four
      failures were most probably due to low viral load or poor quality of RNA and not
      to subtype issues. Some of the sequences obtained from integrase inhibitor-naive
      patients displayed polymorphisms at integrase positions associated with
      resistance: 74IV, 138D, 151I, 157Q and 163AE. The relevance of these
      polymorphisms in the absence of the signature mutations remains unclear.

PMID- 18706933
TI  - The human liver-uPA-SCID mouse: a model for the evaluation of antiviral compounds
      against HBV and HCV.
AB  - The study of the hepatitis B virus (HBV) and the hepatitis C virus (HCV) has long
      been hampered by the lack of a suitable small animal model. Both viruses could
      only be studied in humans or in chimpanzees. Recently, a new chimeric mouse model
      was developed that was permissive for HBV and HCV infection. In this model,
      uPA+/+-SCID mice, suffering from a transgene-induced liver disease, are
      transplanted early after birth with primary human hepatocytes. These human
      hepatocytes integrate in the parenchyma and progressively repopulate the diseased
      mouse liver without losing their normal metabolic functions. Successfully
      transplanted mice can then be infected with HBV and HCV. In this review, we
      describe the characteristics of this chimeric mouse model in more detail and give
      an overview of how this model has already contributed to the development of new
      antiviral compounds for the treatment of viral hepatitis.

PMID- 18706934
TI  - Effects of food deprivation on goal-directed behavior, spontaneous locomotion,
      and c-Fos immunoreactivity in the amygdala.
AB  - Previous work in our laboratory has shown that food deprivation and food
      presentation produce different patterns of neuronal activity (as measured by c
      Fos immunoreactivity) in the medial prefrontal cortex and nucleus accumbens of
      rats. Since the amygdala has been implicated in both motivational and
      reinforcement processes and has neuronal connections to both the prefrontal
      cortex and nucleus accumbens, it was of interest to assess amygdaloid c-Fos
      immunoreactivity during similar manipulations of food deprivation and
      presentation. In the current study, c-Fos counts in both basolateral and central
      amygdalar nuclei were observed to increase in rats 12- and 36-h food deprived
      (relative to 0-h controls)-an effect reversed by the presentation of either a
      small or large meal (2.5 or 20g of food). In another experiment, rats working on
      a progressive ratio schedule of reinforcement exhibited elevated break-points as
      a function of food deprivation, a result consistent with the view that the
      feeding manipulations increased the subjects' level of motivation. In contrast,
      food deprivation reduced the spontaneous locomotor activity of rats, presumably
      as a result of an inherent energy-conservation strategy when no food is readily
      available. These data suggest that the state of food deprivation is associated
      with: (a) enhanced behavioral output only when food is attainable (increased goal
      directed behavior, but decreased spontaneous activity), and (b) increased
      synaptic engagement in neuronal circuits involved in affective valuation and
      related decision-making (increased c-Fos counts in the amygdala).

PMID- 18706935
TI  - The effects of light cycle phase on morphine-induced conditioned taste aversions
      in the Lewis, Fischer and Sprague-Dawley rat strains.
AB  - The present experiment investigated the effect of light cycle phase on morphine
      induced conditioned taste aversions in the Lewis (LEW), Fischer (F344) and
      Sprague-Dawley (SD) rat strains. Separate groups of rats from each strain were
      trained during either the light phase or the dark phase on a procedure in which
      saccharin was paired with one of two doses of morphine (or vehicle). With
      3.2mg/kg morphine, strain differences were observed during the light phase, with
      F344 rats displaying a significantly stronger taste aversion than the LEW rats,
      who displayed a significantly stronger aversion than the SD rats. In contrast,
      during the dark phase, 3.2mg/kg morphine produced comparable, moderately strong
      aversions in all strains. With 10.0mg/kg morphine, F344 rats developed stronger
      aversions than either the LEW or SD rats in both phases of the light cycle. The
      effect of light cycle was most clearly seen in the SD rats, where stronger
      aversions were produced in the dark phase for both morphine doses. For the LEW
      rats, stronger aversions were produced in the dark as compared to the light only
      with the low dose of morphine. For the F344 rats, aversions of comparable
      strength were observed in both phases of the light cycle for both morphine doses.
      The finding that light cycle differentially affects morphine-induced taste
      aversions in these strains is consistent with what is known about strain
      differences in circadian patterns of corticosterone activity and with previous
      results relating corticosterone to morphine-induced taste aversions.

PMID- 18706936
TI  - Preface. Physiological, pathophysiological and therapeutic aspects of 5-HT
      mechanisms.

PMID- 18706937
TI  - A novel spatial Delayed Non-Match to Sample (DNMS) task in the Gottingen minipig.
AB  - The pig (Sus scrofus) is a valuable animal for modeling human brain diseases.
      When evaluating animal models of many human brain disorders cognitive testing is
      crucial, but the pig's ability to learn the typical types of tasks used in
      neuropsychological testing of other species is largely unknown. The present study
      is the first study to evaluate the pig's ability to learn the Delayed Non-Match
      to Sample (DNMS) task. The pigs were trained in a maze on a spatial version of
      the DNMS task. Initially, the pigs were trained with a 60s delay interval between
      sample and test phases, and we found that the pigs required an average of 144
      trials to reach criterion for learning the task, which is similar to macaque
      monkeys. We also found that pigs, in contrast to rats, do not have a natural
      tendency to alternate in their choices in the task. To evaluate the sensitivity
      to reduced memory function longer delay intervals (300 s and 900 s) and a
      scopolamine challenge were introduced. In our test condition we found a
      significant effect of longer delay intervals (F(2,21)=34.43, P<0.0001) and of
      scopolamine (F(1,14)=14.28, P=0.002) on the number of correct choices in the
      task. We conclude that the Gottingen minipig can solve the spatial DNMS task and
      that the task is sensitive to both increasing delay intervals and to scopolamine.

PMID- 18706938
TI  - Long range chromatin interactions involved in gene regulation.
AB  - Long-distance chromatin interaction has been proposed and demonstrated for
      enhancer elements separated from the gene by hundreds or thousands of base pairs.
      This paved the way for the detection of additional enhancer properties, such as
      the regulation of interaction, and the contacting of genes in trans on other
      chromosomes. The outspread arrangement of regulatory elements and transcription
      units requires insulators to prevent the functional interference of enhancer
      elements with inappropriate promoters. Apparently, insulators mediate
      differential chromatin folding to allow or to prevent enhancers from contacting
      specific promoters. The factor CTCF is often involved in bridging separated
      chromatin regions. In addition to interchromosomal contacts, intrachromosomal
      interactions have been demonstrated for genes with a similar regulation, such as
      active genes, estrogen induced genes and imprinted genes. With more sophisticated
      and sensitive methods combined with deep sequencing and array technology, a huge
      number of long range interactions can expected to be characterized in the near
      future.

PMID- 18706939
TI  - The cell biology of DNA methylation in mammals.
AB  - In this review, we will provide a brief reminder of epigenetic phenomena in
      general, and DNA methylation in particular. We will then underline the
      characteristics of the in vivo organization of the genome that limit the
      applicability of in vitro results. We will use several examples to point out the
      connections between DNA methylation and nuclear architecture. Finally, we will
      outline some of the hopes and challenges for future research in the field. The
      study of DNA methylation, its effectors, and its roles, illustrates the
      complementarity of in vitro approaches and cell biology.

PMID- 18706940
TI  - Autophagy: a lysosomal degradation pathway with a central role in health and
      disease.
AB  - Autophagy delivers cytoplasmic material and organelles to lysosomes for
      degradation. The formation of autophagosomes is controlled by a specific set of
      autophagy genes called atg genes. The magnitude of autophagosome formation is
      tightly regulated by intracellular and extracellular amino acid concentrations
      and ATP levels via signaling pathways that include the nutrient sensing kinase
      TOR. Autophagy functions as a stress response that is upregulated by starvation,
      oxidative stress, or other harmful conditions. Remarkably, autophagy has been
      shown to possess important housekeeping and quality control functions that
      contribute to health and longevity. Autophagy plays a role in innate and adaptive
      immunity, programmed cell death, as well as prevention of cancer,
      neurodegeneration and aging. In addition, impaired autophagic degradation
      contributes to the pathogenesis of several human diseases including lysosomal
      storage disorders and muscle diseases.

PMID- 18706941
TI  - Differentiating between isolates of Vibrio vulnificus with monoclonal antibodies.
AB  - Monoclonal antibodies (MAbs) against Vibrio vulnificus (isolate I, VVC and
      isolate II, VVB) were raised using heat-killed and heat-killed plus SDS
      mercaptoethanol treated forms of VVC and VVB for immunizing Swiss mice. Twenty
      three hybridomas producing MAbs against V. vulnificus were selected and divided
      into five groups according to their specificities to different V. vulnificus
      isolates and apparent protein antigens which ranged from approximately 3-50 kDa.
      Four groups were specific to V. vulnificus without cross reactivity to either
      other Vibrio spp. or other bacterial species. In dot blot based assays, one group
      of MAbs were specific to VVC, with a sensitivity of approximately 1.6 x 10(7) CFU
      ml(-1) (approximately 1.6 x 10(4) cells spot(-1)), and bound to proteins of
      approximately 50 and approximately 39 kDa. Other MAbs, binding to proteins
      ranging from approximately 3-14 and approximately 40 kDa, detected VVB (but not
      VVC) with high sensitivity at approximately 1.6 x 10(5) and 4 x 10(6) CFU ml(-1)
      (approximately 1.6 x 10(2) and 4 x 10(3) cells spot(-1)), respectively. In
      addition, certain MAbs were able to recognize V. vulnificus in tissues by means
      of immunohistochemistry. The remaining groups demonstrated cross reactivity to
      Vibrio fluvialis. MAbs from this study can, therefore, detect the difference
      between some isolates of V. vulnificus and in addition to pathogen detection may,
      with further antibodies, form the basis of serovar typing isolates in the future.

PMID- 18706942
TI  - Bacterial artificial chromosome fingerprint arrays for the differentiation of
      transcriptomic differences in mycobacteria.
AB  - Although microarray technology has become more widespread as a discovery tool for
      bacterial pathogenesis, it remains a method available only to laboratories with
      access to expensive equipment and costly analysis software. Mycobacterium
      tuberculosis, the causative agent for tuberculosis (TB), afflicts one-third of
      the global population, and kills between 2 and 3 million people per year. While
      the majority of cases of TB occur in developing areas of the world, facilities in
      these regions may not be able to support microarray analysis. Additionally, a
      major limitation of microarrays is that only genes on the array are being
      assayed. With acquired virulence and drug resistance in microbes, a method less
      dependent on a predetermined list of gene targets is advantageous. We present a
      method of expression analysis based on bacterial artificial chromosomes (BACs)
      that can be applied with standard laboratory equipment and free analysis
      software. This technique, bacterial artificial chromosome fingerprint arrays
      (BACFA), was developed and utilised to identify expression differences between
      intracellular strains of M. tuberculosis, one virulent (H37Rv) and one attenuated
      (H37Ra). Southern blots of restriction-enzyme digested BAC fragments were
      sequentially hybridised with strain-specific cDNA probes to generate expression
      profiles that were used to isolate expression differences in broth grown and
      intracellular bacteria. Repeat comparisons of intracellular profiles via BACFA
      identified genomic regions differentially expressed by the two strains.
      Quantitative real-time PCR was used to assess the genes located in these
      fragments in order to confirm or deny the differential regulation of genes. In
      total, we identified six genes that were differentially regulated between strains
      inside the host cell (pks2, aceE, Rv1571, and frdBCD). We report that BACFA is an
      effective technique in the expression analysis of bacteria and can be considered
      complementary to the high-throughput analysis offered by microarrays.

PMID- 18706943
TI  - Modification to EPA Method 1623 to address a unique seasonal matrix effect
      encountered in some U.S. source waters.
AB  - U.S. Environmental Protection Agency (EPA) Method 1623 is designed to detect and
      determine concentrations of Cryptosporidium oocysts and Giardia cysts in water
      through concentration, immuno-magnetic separation (IMS), and immuno-fluorescence
      assay with microscopic examination. A seasonal interference with the method was
      observed in some municipal source waters collected from reservoirs and as
      reported to Shaw Environmental, Inc. in the summers of 2005, 2006, and 2007. This
      interference, which was not confined to a single region of the nation, caused
      clumping of the IMS beads during the acid dissociation of the IMS procedure in
      Method 1623. This effect lowered method recoveries for both Cryptosporidium and
      Giardia; however, the effect was more pronounced for Giardia. A heat dissociation
      technique (Ware et al., (2003) J. Microbiol. Methods 55, 575-583) was shown to be
      a viable option for samples which demonstrate the clumping matrix effect and
      improved Giardia recoveries in partially clumped samples. The heat dissociation
      application holds promise for fully clumped samples and warrants further
      investigation.

PMID- 18706944
TI  - Development and application of a reverse transcriptase polymerase chain reaction
      to detect Chinese isolates of duck hepatitis virus type 1.
AB  - We developed a reverse transcriptase polymerase chain reaction (RT-PCR) method
      for the detection of duck hepatitis virus type 1 (DHV-1) in the tissues of
      infected and clinically affected ducks and in chick and duck embryos. We found
      the assay to be effective in detecting the virus in China, where it is being used
      in studies on the epidemiology of the disease. We applied this simple and rapid
      diagnostic method to the detection of DHV isolates grown in chick and duck
      embryos and in tissues obtained from infected birds. The assay also proved useful
      for the differentiation of DVH from the duck plague virus (DPV), muscovy
      parvovirus (MPV), gosling parvovirus (GPV), avian influenza virus (AIV/H5N1),
      Pasteurella multocida (PA/5:A), Riemerella anatipestifer (RA/serotype 1), and
      Salmonella enteritidis (SE). The limit of the sensitivity of this method for the
      detection of DHV-1 RNA was 3 pg/10 microl. As compared to ELISA and virus
      isolation, the rate of agreement for the detection of experimentally infected
      livers was 100%; moreover, the RT-PCR method was also capable of detecting DHV-1
      RNA from the livers that had been infected and stored at -20 degrees C for 22
      years; in contrast, ELISA and virus isolation method could only detect DHV-1 from
      the livers that had been infected and stored at -20 degrees C for 13 and 11
      years, respectively. The rate of positivity in 185 clinically suspected diseased
      livers subjected to detection by RT-PCR, ELISA, and virus isolation was 89.2%,
      69.2%, and 55.7%, respectively. These results indicated that the RT-PCR approach
      is rapid, sensitive, and reliable for the detection and differentiation of DHV-1
      from the other clinical samples and suspected isolates.

PMID- 18706945
TI  - The structure-function relationship of the enterovirus 3'-UTR.
AB  - Essential processes in living cells are carried out by large complex assemblies,
      which typically consist of a large number of proteins and frequently also contain
      nucleic acids, mostly RNA [Alberts, B., 1998. The cell as a collection of protein
      machines: preparing the next generation of molecular biologists. Cell 92, 291
      294]. These large biomolecular complexes carry out biological processes in highly
      sophisticated ways: molecules do not move around randomly in the cell and
      interact by chance, but are guided to these "macromolecular machines", in which
      the number of possible collisions is restricted to a few possibilities, based,
      e.g., on the specificity of protein-RNA recognition. While the coding capacity of
      RNA lies within its sequence, the shape of an RNA molecule determines other
      functionalities such as stability, intra- and intermolecular interactions,
      catalytic activity, regulation of cellular processes, etc. [Doudna, J.A., 2000.
      Structural genomics of RNA. Nat. Struct. Biol. 7, 954-956; Cech, T.R. 2000.
      Structural biology. The ribosome is a ribozyme. Science 289, 878-879]. RNA
      structures in macromolecular machines are important features in assembly, target
      recognition and activity. Viral RNA molecules contain cis- and/or trans-acting
      control elements that, as exemplified by internal ribosomal entry sites and
      origins of genome replication, consist of complex multidomain structures [Andino,
      R., Rieckhof, G.E., Achacoso, P.L., Baltimore D., 1993. Poliovirus RNA synthesis
      utilizes an RNP complex formed around the 5'-end of viral RNA. EMBO J. 12, 3587
      3598; Melchers, W.J.G., Hoenderop, J.G.J., Bruins Slot, H.J., Pleij, C.W.A.,
      Pilipenko, E.V., Agol, V.I., Galama, J.M.D., 1997. Kissing of the two predominant
      hairpin loops in the coxsackie B virus 3' untranslated region is the essential
      structural feature of the origin of replication required for negative-strand RNA
      synthesis. J. Virol. 71, 686-696]. The formation of these structures is involved
      in the specific recognition of ligands or serves to support the structural
      integrity of the whole element. The replication of the enterovirus RNA is carried
      out by a large biomolecular complex formed by cis-acting RNA elements found in
      the 5'- and 3'-UTR of the virus genome and several cellular and viral proteins.
      This review will focus on RNA elements in the 3'-UTR of enteroviruses.

PMID- 18706946
TI  - Galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine as a gene
      carrier for hepatocyte-targeting.
AB  - Chitosan and chitosan derivatives have been proposed as alternative and
      biocompatible cationic polymers for non-viral gene delivery. However, the low
      transfection efficiency and low specificity of chitosan is an aspect of this
      approach that must be addressed prior to any clinical applications. In the
      present study a chitosan derivative, galactosylated poly(ethylene glycol)
      chitosan-graft-polyethylenimine (Gal-PEG-CHI-g-PEI), was investigated as a
      potential hepatocyte-targeting gene carrier. The composition of Gal-PEG-CHI-g-PEI
      was characterized using (1)H nuclear magnetic resonance ((1)H NMR), and the
      particle size and zeta potential of Gal-PEG-CHI-g-PEI/DNA complexes were measured
      using dynamic light scattering (DLS). The Gal-PEG-CHI-g-PEI exhibited lower
      cytotoxicity compared to PEI 25K as a control. Likewise, Gal-PEG-CHI-g-PEI/DNA
      complexes showed good hepatocyte specificity. Furthermore, Gal-PEG-CHI-g-PEI/DNA
      complexes transfected liver cells more effectively than PEI 25K in vivo after
      intravenous (i.v.) administration. Together, these results suggest that Gal-PEG
      CHI-g-PEI, which has improved transfection efficiency and hepatocyte specificity
      both in vitro and in vivo, may be useful for gene therapy.

PMID- 18706947
TI  - Bioresponsive drug delivery for regenerative medicine.

PMID- 18706948
TI  - Effects of Salmonella enterica serovar Enteritidis on cellular recruitment and
      cytokine gene expression in caecum of vaccinated chickens.
AB  - Although vaccination of poultry is a suitable method to limit human food borne
      gastroenteritis caused by Salmonella (S.), the immune mechanisms responsible for
      a longer lasting protection against Salmonella infection in birds are not
      completely understood. To reveal unique protection-related immune parameters, day
      old chicks were vaccinated with a commercial live S. Enteritidis vaccine and
      challenged with wild-type S. Enteritidis 147N at day 56 of life. The bacterial
      cell count was determined in gut and liver, while the immune cell composition and
      cytokine gene expression patterns were analysed by immunohistochemistry and
      quantitative real-time RT-PCR in caecum samples. The presented data suggest that
      the vaccine-elicited immune protection against the Salmonella wild-type infection
      was rather related to the bacterial count in gut mucosa and liver than to the
      colonisation in gut lumen. The higher number of Salmonella wild-type organisms
      found in caecal wall and liver of the non-immunised compared to immunised birds
      after challenge correlated with a more pronounced gene expression rate for IL-8,
      LITAF, iNOS, IL-12 and IFN-gamma. In contrast, immunised birds exhibited higher
      amounts of CD8(+) T cells as well as IgA than the non-immunised chickens after S.
      Enteritidis 147N infection in caecum. The results demonstrated a distinctive
      immune reaction pattern of previously vaccinated compared to non-vaccinated
      chickens upon S. Enteritidis wild-type challenge.

PMID- 18706949
TI  - Efficacy and safety of cell associated vaccines against Marek's disease virus
      grown in a continuous cell line from chickens.
AB  - The Marek's disease virus (MDV) vaccine strains CVI 988 and herpes virus of
      turkeys (HVT) strain FC126, usually are grown in primary chicken embryo
      fibroblasts (CEF). We found that the strains could be grown also in the so-called
      JBJ-1 cell line to titres in the same range as when chicken embryo fibroblasts
      were used. The JBJ-1 cell line is a fibroblast-like continuous chicken cell line,
      which can be grown in flat bottom tissue culture flasks, roller bottles and on
      micro carriers. We investigated the efficacy of experimental CVI 988 vaccines
      grown in JBJ-1 cells and the efficacy of combinations of CVI 988 grown in JBJ-1
      cells with HVT FC 126 also grown in JBJ-1 cells. The study was performed in
      accordance with European Pharmacopoeia monograph 0589 for live MDV disease
      vaccines. Groups of 1-day-old SPF chicks were vaccinated subcutaneously or
      intramuscularly, with 10(2.5) TCID50 per dose of CVI 988 alone or in combination
      with 500PFU per dose of HVT. As a control a group vaccinated with CVI 988 grown
      in CEF was included. One group was not vaccinated. Five days after vaccination
      all chickens were challenged with the very virulent MDV strain RB1B. After
      challenge the chickens were observed for a period of 70 days for signs of Marek's
      disease (MD). The protection induced by CVI 988 grown in JBJ-1 cells and the
      combination of CVI 988 and HVT-FC126 both grown in JBJ-1 cells, amply complied
      with the requirements of the European Pharmacopoeia which prescribes that the
      protection index should be at least 80%. The safety of the vaccines grown in JBJ
      1 cells was tested in a field study in commercial layer chickens. No signs of MD
      were noticed during the study and no other signs attributable to the vaccine. It
      is concluded that the JBJ-1 cell line is a suitable substrate for the current
      vaccines against MD.

PMID- 18706950
TI  - Immunization: mind the gap.

PMID- 18706951
TI  - DNA sequence analysis of varicella-zoster virus gene 62 from subclinical
      infections in healthy children immunized with the Oka varicella vaccine.
AB  - A live attenuated varicella vaccine, the Oka vaccine strain (vOka), is routinely
      administered to children in Japan and other countries, including the United
      States. vOka consists of a mixture of genotypically distinct variants, but little
      is known about the growth potential of each variants in vivo. We isolated
      varicella-zoster virus (VZV) DNA sequences from the peripheral blood mononuclear
      cells (PBMCs) of asymptomatic healthy children immunized with the Oka varicella
      vaccine. VZV gene 62 DNA fragments were detected in 5 of 166 (3.0%) PBMC samples
      by nested PCR within 5 weeks of the vaccination. Sequence analysis of VZV DNA
      from these five PBMC samples indicated that multiple viral clones in the vaccine
      could infect vaccinees and replicate in vivo. We also provide evidence that a
      nonsynonymous substitution at position 105356 may affect viral replication in
      vivo.

PMID- 18706952
TI  - The need for public education on HPV and cervical cancer prevention in Asia.
      Opinions of experts at the AOGIN conference.
AB  - Asia accounts for more than half of all cases of cervical cancer registered
      globally and improving prevention is urgently needed. A range of tools and
      strategies is now available to effectively prevent this disease, including two
      new prophylactic HPV vaccines approved and recommended for adolescents and young
      women. However, without communication these tools may have little impact on
      disease burden. The conferences of the Asia Oceania Research Organisation in
      Genital Infection and Neoplasia (AOGIN) bring together clinicians and scientists
      whose work is related to genital infections, particularly HPV, cervical dysplasia
      and neoplasia, as well as other anogenital cancers, with the aim of improving
      communication on prevention through human papillomavirus (HPV) vaccination and
      screening in Asian countries. The scope of this year's AOGIN conference was to
      extend education to include health workers, family doctors, paediatricians,
      governmental health agencies, and the general public through patients'
      testimonials that can reach out to women raising awareness of this silent
      disease. Community based initiatives and awareness campaigns were also reported,
      and can empower the people to engage in a dialog with local governments towards
      prioritization of cancer prevention programs, achieving more for the public than
      isolated actions. Parents and teachers are encouraged to communicate about these
      issues within families and schools. Evidence was discussed that males can
      participate in cervical cancer control as well, and prevention programs involving
      men should not be neglected as they may reduce genital disease burden in women.
      Opinion leaders proposed prevention measures to be considered for governmental
      decisions. While each country develops a locally appropriate policy for cervical
      cancer control there is a need to revise these programs regularly, as knowledge
      increases in response to public need, as well as to gather evidence about disease
      burden and the effectiveness of education and interventions. In conclusion, AOGIN
      is committed to improve communication with patients, health authorities,
      professional organizations and opinion leaders towards strengthening cervical
      cancer prevention in Asia, to achieve a timely steep reduction in this cancer.

PMID- 18706953
TI  - Immunogenic properties of plant-derived recombinant smallpox vaccine candidate
      pB5.
AB  - The extracellular virion membrane protein B5 is a potent inducer of immune
      responses capable of protecting mice and primates against poxvirus infections.
      Here, we examined the antibody response induced in mice immunized intramuscularly
      (i.m.) or intranasally (i.n.) with plant-derived B5 (pB5) accompanied or not with
      plant total soluble protein (TSP) at various concentrations. Increasing amounts
      of TSP inhibited the pB5-specific response in both i.m.- and i.n.-immunized mice,
      with more dramatic effects in the latter. pB5 administered to mucosal surfaces
      induced specific IgG and IgA responses, whereas i.m. immunization produced high
      serum IgG titers and no IgA. A 6-fold increase in pB5 dosage administered i.n.
      led to an antibody response comparable to that obtained by i.m. injection. Our
      study addresses the quality/quantity issues of the pB5 subunit preparation and
      demonstrates the feasibility of mucosal administration of plant-derived smallpox
      subunit vaccine in obtaining a potent immune response. Overall, this work points
      to the practicability of needle-free mucosal administration of such vaccines in
      light of purity, dosage and adjuvant formulation.

PMID- 18706954
TI  - Exercise enhances vaccine-induced antigen-specific T cell responses.
AB  - Regular moderate exercise has been proposed to enhance immune function, but its
      effects on immunity and their consequences have not been well studied. Mice
      without (AL) or with access (AL+EX) to voluntary running wheels were vaccinated
      with a model antigen (ovalbumin (OVA)) via intranasal or subcutaneous routes to
      target the mucosal and systemic immune compartments, respectively. EX enhanced
      OVA-specific CD4(+) T cell cytokine production and proliferation in all lymphoid
      organs examined without changes in cell distribution in any organ. These results
      suggest that coupling moderate exercise with vaccination may enhance vaccine
      efficacy for the prevention and/or therapy of numerous diseases.

PMID- 18706955
TI  - Differences in attitudes, beliefs and knowledge of hospital health care workers
      and community doctors to vaccination of older people.
AB  - Pneumococcal disease and influenza are major causes of morbidity and mortality
      particularly among the elderly. Influenza and pneumococcal vaccination are
      recommended for people aged 65 years and older or persons with chronic illness.
      However, despite the burden of disease related to pneumococcus and influenza and
      the availability safe, efficacious and cost-effective vaccines, health care
      providers continue to have doubts about these vaccines. Little is known about
      barriers for pneumococcal vaccination in the health care providers particularly
      in the primary health care setting. Since 2005 a publicly funded program offering
      free pneumococcal vaccine for elderly people over 65 years has been implemented
      in Australia. AIM: To investigate knowledge, attitudes and practices around
      vaccination of elderly patients among hospital health care workers and community
      general practitioners and to explore the difference between hospital doctors and
      GP. METHODS: A self-reported questionnaire survey distrubuted March and June 2007
      to General physicians (GP's) whose practices are located in Western Sydney and
      health care staff consisting of Hospital Doctors (HD), hospital nurses (HN) and
      allied health care workers at a tertiary referral hospital in Western Sydney.
      Descriptive analyses were conducted; bivariate analyses were performed to
      investigate associations between variables. RESULTS: Completed surveys were
      obtained for 56.3% (335/595) GPs and 42.1% (346/822) for HHCWs. The HHCWs
      comprised 37.5% (130/346) HD, 57.8% (200/346) HN and 4.6% (16/346) allied health
      care workers. GP's are more likely to support elderly vaccination than hospital
      doctors (98.8% compared to 93%, P=0.0007). GPs reported that the reason for not
      vaccinating patients in 88% (295/335) of the cases was due to patient refusal.
      GP's and HHCW both agreed that pneumococcal disease is a serious illness and that
      vaccination is an important preventive measure for the elderly. However, the
      majority 68.2% (88/129) of hospital doctors report that vaccinations are
      difficult to address due to multiple competing priorities compared to only 34.6%
      (116/335) of GPs, P<0.0001. Hospital doctors are more likely than GPS (24% vs.
      17%) to report that patients often complain of adverse effects from pneumococcal
      vaccine. Hospital doctors 20% (104/130) are significantly less likely than GPs<1%
      (3/335) to have access to guidelines and other information regarding vaccination
      in the elderly. CONCLUSIONS: GPs and hospital health care workers in our study
      were aware of, agreed with, immunization recommendation for the pneumococcal
      vaccine. Physician barriers to vaccination were patient's refusals and competing
      priorities, particularly for hospital health care workers, who were less likely
      to see vaccination as a priority. Hospitalisation is an opportunity for
      vaccination, but utilisation of this opportunity is reduced by lack of access to
      information about immunization for hospital health care workers and competing
      priorities. These could be areas to target for improved uptake of the elderly
      immunization.

PMID- 18706956
TI  - H5N1 VLP vaccine induced protection in ferrets against lethal challenge with
      highly pathogenic H5N1 influenza viruses.
AB  - In this study, recombinant virus-like particles (VLPs) were evaluated as a
      candidate vaccine against emerging influenza viruses with pandemic potential. The
      VLPs are composed of the hemagglutinin (HA), neuraminidase (NA), and matrix 1
      (M1) proteins of the H5N1 A/Indonesia/05/2005 (clade 2.1; [Indo/05]) virus, which
      were expressed using baculovirus in Spodoptera frugiperda (Sf9) cells. Ferrets
      received either 2 injections of the VLP vaccine at escalating doses (based on HA
      content), recombinant HA, or were mock vaccinated. Vaccinated ferrets were then
      challenged with either H5N1 Indo/05 or H5N1 A/Viet Nam 1203/2004 (VN/04) wild
      type viruses. All ferrets that received the VLP vaccine survived regardless of
      the VLP dose or challenge strain, whereas seven of eight mock vaccinated ferrets
      died. The VLP vaccine induced HAI antibodies against the homologous H5N1 clade
      2.1 strain, as well as heterologous strains from H5N1 clades 1, 2.2, and 2.3. The
      magnitude of the HAI titers correlated with VLP dose. Neutralizing antibody
      responses against the Indo/05 and VN/04 strains showed a similar pattern.
      Affinity of the anti-HA antibodies raised by the H5N1 Indo/05 VLPs had a higher
      association rate to the homologous clade 2.1 HA than to the clade 1 (VN/04) HA;
      however, once bound, antibodies had similar slow disassociation rates. These
      results provide support for continued development of the H5N1 VLPs as a candidate
      vaccine against pandemic influenza. Exploration of immunologic correlates of
      protection for H5N1 vaccines beyond HAI and neutralizing antibody responses is
      warranted.

PMID- 18706957
TI  - The cost-effectiveness of using hepatitis A/B combined vaccine versus hepatitis B
      vaccine alone for high-risk heterosexuals.
AB  - Previous studies estimated that vaccinating high-risk heterosexuals (HRH) with
      combination hepatitis A/B vaccine was a cost-effective alternative to vaccinating
      HRH against hepatitis B alone. Since then, the incidence of hepatitis A has
      declined dramatically in the United States. We re-estimate the cost-effectiveness
      of this policy accounting for modern declines in incidence. According to our
      estimates, vaccinating with combination vaccine resulted in a cost of $120,000
      per quality adjusted life year gained (2.79 times the 2005 United States Gross
      Domestic Product per capita), a ratio that is less favorable than those for most
      other vaccination strategies.

PMID- 18706958
TI  - Virus-like particles from rabbit hemorrhagic disease virus can induce an anti
      tumor response.
AB  - Recombinant virus-like particles (VLP) expressing heterologous tumor antigens
      have recently been investigated for use as vaccines. We have chemically
      conjugated ovalbumin (OVA) or OVA-derived CD4 (OTII) and CD8 (OTI) epitopes, to
      rabbit hemorrhagic disease virus (RHDV) VLP. VLP conjugated with OVA were able to
      cross-prime CD8+ cells from OT1 mice transgenic for the OVA T cell receptor.
      VLP.OTI was able to induce higher antigen-specific cytotoxicity in vivo than VLP
      mixed with either the protein or the peptide. Furthermore we have shown that the
      growth of the aggressive B16.OVA melanoma in mice was significantly delayed in
      those animals that had been vaccinated with VLP.OVA or with VLP coupled with both
      OTI and OTII peptides prior to the introduction of the tumor. Neither VLP.OTI nor
      VLP.OTII alone were capable of inhibiting tumor growth. This work suggests that
      RHDV VLP offer a versatile scaffold for multiple vaccine epitopes, enabling cross
      presentation of the antigen to elicit potent cell-mediated and anti-tumor
      responses.

PMID- 18706959
TI  - Development and immunogenicity of recombinant Mycoplasma gallisepticum vaccine
      strain ts-11 expressing chicken IFN-gamma.
AB  - Mycoplasma gallisepticum (MG) is a poultry pathogen that causes respiratory
      disease and loss of egg production worldwide. A live attenuated vaccine, ts-11,
      has been used for the control of MG in several countries. To improve the
      functionality of the vaccine and investigate its potential as a delivery vector
      for host immune molecules and foreign antigens, we have developed ts-11 as a
      vector to express and secrete chicken IFN-gamma (ts-11 C3) using a transposon
      based delivery vector. Following administration of ts-11 C3 in chickens by eye
      drop, up to 2 weeks post-vaccination, neither significant systemic IFN-gamma
      expression nor an antibody response as determined by the rapid serum
      agglutination (RSA) could be detected, while moderate RSA scores were detected in
      birds vaccinated with ts-11. However, the MG-specific IFN-gamma response in
      spleen cultures was significantly enhanced in ts-11 C3 vaccinated chickens and,
      more interestingly, significant heterophil infiltration was detected in the
      tracheal epithelium in ts-11 C3 vaccinated birds, but not in ts-11 vaccinated
      birds. These results indicate that the IFN-gamma expressed by ts-11 C3 enhanced
      host cellular immunity rather than humoral immunity and may also have stimulated
      mucosal heterophil infiltration. These results also suggest that ts-11 is a
      promising vector for protective antigens of other chicken respiratory pathogens.

PMID- 18706961
TI  - The serum bank of EuroPrevall - the prevalence, cost and basis of food allergy
      across Europe.
AB  - EuroPrevall is an EU-funded multidisciplinary project including 62 institutions
      from 22 countries. EuroPrevall studies the prevalence and distribution of food
      allergies in infants, children, adolescents, and adults in Europe, threshold
      doses for allergenic foods, the role of the environment in food allergy, the
      socioeconomic impact of food allergy, and novel diagnostic tools for food
      allergies. The EuroPrevall serum bank (EPASB), containing samples from
      approximately 70,000 subjects, is a major tool to achieve these goals. EPASB is
      coordinated by the Paul-Ehrlich-Institut, Langen, Germany. Local sera collections
      are administered at the University of Amsterdam (NL), the University Hospital of
      Manchester (UK), Charite Hospital (DE) and the Paul-Ehrlich-Institut. The EPASB
      coordinator and managing partners distribute samples for experimental work and
      regulate access. The overall aim is to provide sera to fulfil EuroPrevall
      research goals. The EPASB coordinator and managing partners suggest appropriate
      sera for addressing specific scientific and diagnostic questions. The serum bank
      will be maintained after termination of the project, but subsequent
      investigations must be in accordance with the original research goals of
      EuroPrevall. Thus, the contributors of the sera retain control over their future
      use. This rule prevents investigation of questions outside the scope of
      EuroPrevall, e.g. the allergenicity of genetically-modified foods.

PMID- 18706962
TI  - Molecular profiles: a new tool to substantiate serum banks for evaluation of
      potential allergenicity of GMO.
AB  - Assessment of the allergenicity of GMOs involves performing a test with a panel
      of sera obtained from allergic donors. However, there is no clear indication of
      how to characterize the above-mentioned panel. The patient selection criteria
      should take into account the geographical location of patients, the intensity and
      nature of the environmental allergens in the area and the potential cross
      reactivity among allergenic molecules. Sera for serum banks, obtained from
      patients with demonstrated food allergy, should be subjected to a further
      characterization by screening with a panel of relevant allergenic molecules. A
      representative panel of these sera should be used in the allergenicity
      assessment. Finally, the "in vitro" methodologies should have the adequate
      specificity and sensitivity, and the integrity of the molecules tested should be
      guaranteed.

PMID- 18706963
TI  - Atopic dermatitis and allergy in children: a dynamic relationship.
AB  - Atopic dermatitis (AD) is the most common chronic skin disease in children. The
      defective barrier function of the skin in patients with AD allows foreign
      proteins to enter the body and interact with components of the innate and
      adaptive immune systems. The immune response characteristic of AD is complex with
      the majority of patients making IgE in response to ingested and/or inhaled
      antigens. Although IgE-mediated mechanisms may represent initial immune
      responses, they are only one element of a biphasic inflammatory response.
      Identifying the role of specific allergens in a patient's skin disease is
      critical yet difficult because diagnostic tests are often not able to distinguish
      asymptomatic sensitization from true clinical allergy.

PMID- 18706964
TI  - Effects of EGCG on voltage-gated sodium channels in primary cultures of rat
      hippocampal CA1 neurons.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), the main active component of green tea, is
      commonly known for its beneficial properties at low doses. On the other hand,
      little is known about the adverse effects of EGCG. Voltage-gated sodium channel
      (VGSC) is responsible for both initiation and propagation of action potentials of
      the neurons in the hippocampus and throughout the central nervous system (CNS).
      In this study, the effects of EGCG on voltage-gated sodium channel currents
      (I(Na)) were investigated in rat primary cultures of hippocampal CA1 neurons via
      the conventional whole-cell patch-clamp technique. We found that I(Na) was not
      affected by EGCG at the concentration of 0.1microM, but was completely blocked by
      EGCG at the concentration of 400microM and higher, and EGCG reduced the
      amplitudes of I(Na) in a concentration-dependent manner in the range of 0.1
      400microM. Furthermore, our results also showed that at the concentration of
      100microM, EGCG was known to have the following performances: (1) it decreased
      the activation threshold and the voltage at which the maximum I(Na) current was
      evoked, caused negative shifts of I(Na) steady-state activation curve. (2) It
      enlarged I(Na) tail-currents. (3) It induced a left shift of the steady-state
      inactivation. (4) It reduced fraction of available sodium channels. (5) It
      delayed the activation of I(Na) in a voltage-dependent manner. (6) It prolonged
      the time course of the fast inactivation of sodium channels. (7) It accelerated
      the activity-dependent attenuation of I(Na). On the basis of these findings, we
      propose that EGCG could impair certain physiological functions of VGSCs, which
      may contribute, directly or indirectly, to EGCG's effects in CNS.

PMID- 18706965
TI  - Antimicrobial action of histone H2B in Escherichia coli: evidence for membrane
      translocation and DNA-binding of a histone H2B fragment after proteolytic
      cleavage by outer membrane proteinase T.
AB  - Previous studies have led to the isolation of histone H2B with antibacterial
      properties from an extract of the skin of the Schlegel's green tree frog
      Rhacophorus schlegelii and it is now demonstrated that the intact peptide is
      released into norepinephrine-stimulated skin secretions. In order to investigate
      the mechanism of action of this peptide, a maltose-binding protein (MBP)-fused
      histone H2B (MBP-H2B) conjugate was prepared and subjected to antimicrobial
      assay. The fusion protein showed bacteriostatic activity against Escherichia coli
      strain JCM5491 with a minimum inhibitory concentration of 11 microM. The lysate
      prepared from JCM5491 cells was capable of fragmenting MBP-H2B within the histone
      H2B region, but the lysate from the outer membrane proteinase T (OmpT) gene
      deleted BL21(DE3) cells was not. FITC-labeled MBP-H2B (FITC-MBP-H2B) penetrated
      into the bacterial cell membrane of JCM5491 and ompT-transformed BL21(DE3) cells,
      but not into ompT-deleted BL21(DE3) cells. Gel retardation assay using MBP-H2B
      deletion mutants indicated that MBP-H2B bound to DNA at a site within the N
      terminal region of histone H2B. Consequently, it is proposed that the
      antimicrobial action of histone H2B involves, at least in part, penetration of an
      OmpT-produced N-terminal histone H2B fragment into the bacterial cell membrane
      with subsequent inhibition of cell functions.

PMID- 18706966
TI  - Streptococcus agalactiae DNA polymerase I is an efficient reverse transcriptase.
AB  - Genome annotations result generally from large sequence alignments by
      bioinformatics. Large scale biochemical data are more difficult to obtain. They
      derive for example from directed protein evolution experiments by selection. A
      previously reported directed enzyme evolution experiment by in vitro selection of
      Stoffel fragment variants of Taq DNA polymerase I was used here to predict the
      activities of Streptococcus agalactiae DNA polymerase I. The reverse
      transcriptase activity of S. agalactiae DNA polymerase I was measured and the
      kinetic parameters for this RNA-dependent DNA polymerase are given. RNA-templated
      DNA repair is suggested as a possible biological function for this biochemical
      activity.

PMID- 18706967
TI  - Distribution and roles of X-family DNA polymerases in eukaryotes.
AB  - Four types of DNA polymerase (Pol beta, Pol lambda, Pol mu and TdT) have been
      identified in eukaryotes as members of the polymerase X-family. Only vertebrates
      have all four types of enzyme. Plants and fungi have one or two X-family
      polymerases, while protostomes, such as fruit flies and nematodes, do not appear
      to have any. It is possible that the well-known metabolic pathways in which these
      enzymes are involved are restricted to the vertebrate world. The distribution of
      the DNA polymerases involved in DNA repair across the various biological kingdoms
      differs from that of the DNA polymerases involved in chromosomal DNA replication.
      In this review, we focus on the interesting pattern of distribution of the X
      family enzymes across biological kingdoms and speculate on their roles.

PMID- 18706968
TI  - Salivary dehydroepiandrosterone secretion in response to acute psychosocial
      stress and its correlations with biological and psychological changes.
AB  - We investigated dehydroepiandrosterone (DHEA) secretion in response to acute
      psychosocial stress and the relations of DHEA secretion to cortisol secretion,
      cardiovascular activity, and negative mood changes. Thirty-three male students
      (mean age 22.6 years) were subjected to the psychosocial stress test "Trier
      Social Stress Test" (TSST), in which the participants were asked to deliver a
      speech and perform a mental arithmetic task in front of two audiences.
      Collections of saliva, measurements of blood pressure and heart rate, and
      assessments of negative mood by visual analog scales were conducted before,
      during, and after TSST. Acute psychosocial stress significantly increased
      salivary DHEA level by an average of 60% immediately after TSST. The peak of DHEA
      concentration preceded that of cortisol concentration by about 10 min. DHEA
      response was moderately correlated to cortisol response (r=.34, r(s)=.49) but not
      to cardiovascular response. Lower DHEA level and elevated cortisol/DHEA ratio
      during TSST were significantly and moderately correlated with increased negative
      mood during and after TSST. These results indicated that an acute increase in
      DHEA concentration under stressful situations might be partly mediated by the
      activity of hypothalamus-pituitary-adrenal axis and could have some significance
      in the improvement of negative mood.

PMID- 18706969
TI  - Gaia again.
AB  - The ideas of the Gaia hypothesis from the 1960s are today largely included in
      global ecology and Earth system sciences. The interdependence between biosphere,
      oceans, atmosphere and geosphere is well-established by data from global
      monitoring. Nevertheless the theory underlying the holistic view of the
      homeostatic Earth has remained obscure. Here the foundations of Gaia theory are
      examined from the recent formulation of the 2nd law of thermodynamics as an
      equation of motion. According to the principle of increasing entropy, all natural
      processes, inanimate just as animate, consume free energy, the thermodynamic
      driving force. All species, abiotic just as biotic are viewed as mechanisms of
      energy transduction for the global system to evolve toward a stationary state in
      its surroundings. The maximum entropy state displays homeostasis by being stable
      against internal fluctuations. When surrounding conditions change or when new
      mechanisms emerge, the global system readjusts its flows of energy to level newly
      appeared gradients. Thus, the propositions of Gaia theory and holistic
      understanding of the global system are recognized as consequences of
      thermodynamic imperatives.

PMID- 18706970
TI  - Stability analysis of a model for HIV infection with RTI and three intracellular
      delays.
AB  - We consider a model of HIV-1 infection with a reverse transcriptase inhibitor
      (RTI) therapy and three delays: the first delay is defined as the time from the
      virus entry into the target cell to the reverse transcriptase step, the second
      delay represents the time from the virus entry to the production of new viruses
      and the third delay corresponds to the time necessary for a newly produced virus
      to become infectious. We analyse the stability of the steady states and determine
      a threshold value for the first delay at which the system exhibits a Hopf
      bifurcation. This might explain the clinically observed transient elevated
      viremia called viral blips. The frequency of the bifurcating periodic solution as
      well as the threshold value is approximated numerically using realistic
      parameter. The estimated threshold value is realistic and the frequency of the
      oscillations is consistent with that of the observed viral blips.

PMID- 18706971
TI  - Inactivation of the ventromedial prefrontal cortex mimics re-emergence of heroin
      seeking caused by heroin reconditioning.
AB  - The purpose of this study was to investigate the role of the ventromedial
      prefrontal cortex (vmPFC) in the expression of extinguished heroin seeking as
      measured by conditioned place preference (CPP) in males Sprague-Dawley rats
      (n=25). Heroin place conditioning (0.3mg/kg SC x 4 sessions) was followed by a
      test of preference 24h later, extinction (saline x 4 sessions), heroin
      reconditioning (saline or 1.0mg/kg x 1 session), and a second test of place
      preference 24h later. Fifteen minutes prior to this test, rats received intra
      vmPFC infusions (bilateral, 0.5 microl/side) of a mixture of GABA(A) (muscimol;
      0.03 nmol) and a GABA(B) (baclofen; 0.3 nmol) agonists, or vehicle. As expected
      on the basis of previous studies, reconditioning with heroin resulted in the re
      emergence of a CPP. Importantly, inactivation of the vmPFC produced the same
      effect in animals that did not receive heroin on the session of reconditioning.
      These results indicate that the vmPFC modulates expression of extinguished heroin
      seeking and suggest that prefrontal inhibitory mechanisms are involved in relapse
      to drug seeking.

PMID- 18706972
TI  - Mitochondrial DNA haplogroups do not influence the Huntington's disease
      phenotype.
AB  - Various lines of evidence demonstrate the involvement of mitochondrial
      dysfunction in the pathogenesis of Huntington's disease (HD). However, the
      precise role of mitochondria in the neurodegenerative cascade leading to HD is
      still unclear. Mitochondrial DNA (mtDNA) haplogroups-specific polymorphisms were
      previously related to several neurodegenerative diseases. The length of CAG
      repeat seems to be related to the clinical features of HD, such as age of onset
      and progression of motor impairment. The basis for the impaired cognitive
      functions and for the mood changes is less clear. Aim of this study was to
      determine whether mtDNA polymorphism(s) play the role of "modifier gene(s)" in
      this disease. In this work we have genotyped predefined European mtDNA
      haplogroups in 51 patients with HD and 181 matched controls. The frequency of the
      haplogroups and haplogroup clusters did not differ between the two groups, and no
      correlation with gender, age of onset and disease status was observed. No
      significant difference was observed between different haplogroups and haplogroup
      clusters in the cognitive or motor progression of the disease. Our study does not
      support any association between mtDNA haplogroups and HD.

PMID- 18706973
TI  - Raf inhibition protects cortical cells against beta-amyloid toxicity.
AB  - Alzheimer's disease (AD) is the main cause of dementia in the elderly. The
      discovery of new targets of therapeutic intervention is fundamental to the
      development of new drugs against AD pathology. Upregulation of cRaf-1 has been
      found post-mortem in the brains of AD patients. cRaf-1 is a cytosolic protein
      kinase that regulates neuronal survival and senescence. In this study, we
      investigated cRaf-1 in the brains of aged APPswe mice presenting AD-like
      pathology and whether Raf inhibitors protected cultured cortical cells against
      amyloid beta toxicity (Abeta). We found a dysregulation of cRaf-1 in the cortex
      of APPswe mice, which showed a 147% increase in the active form phosphorylated at
      serine 338 and a 40% decrease in the levels of the inactive form of cRaf-1,
      phospho-cRaf-1[Ser259]. Furthermore, treatment of primary cortical neurons with
      the cRaf-1 inhibitors, GW5074 or ZM336372, and the nuclear factor kappa B
      (NFkappaB) inhibitor SN50, protected cortical neurons against Abeta toxicity.
      Since Raf stimulates NFkappaB, we studied the effect of Raf inhibition on its
      activation by studying changes in NFkappaB phosphorylation at serine 276. Our
      results suggest that Raf inhibition with GW5074 is neuroprotective against Abeta
      toxicity through a mechanism that involves NFkappaB inhibition.

PMID- 18706974
TI  - Heme oxygenase expression and activity in immortalized hypothalamic neurons GT1
      7.
AB  - Heme oxygenase (HO), the main enzyme deputed to heme metabolism, has been
      identified as two main isoforms called HO-1 and HO-2. HO-1 is inducible and plays
      a main role in the cellular oxidant/antioxidant balance whereas HO-2 is
      constitutive and involved in the physiological metabolism of heme. However, it is
      noteworthy to mention that HO contribute to the regulation of the hypothalamic
      release of neuropeptides such as corticotrophin-releasing hormone and arginine
      vasopressin and could modulate the pulsatile release of gonadotropin releasing
      hormone (GnRH). GT1-7 cells are immortalized hypothalamic neurons and a valuable
      tool to evaluate hypothalamic neuroendocrine control of reproduction. The aim of
      this work was to investigate and characterize the presence of HO isoforms in the
      GT1-7 hypothalamic neurons. Hemin, a well-known inducer of HO-1, significantly
      increased HO activity, whereas dexamethasone did not modify HO-2 activity.
      Moreover, hemin and DEX, in combination, did not have any additive effect on HO
      activity in GT1-7 neurons. Furthermore, basal HO-1 immunoreactivity identified in
      GT1-7 cells, was significantly up-regulated by hemin. Conversely, no HO-2
      immunoreactivity was detected. Taken together, these results suggest the presence
      of functional HO-1 in GT1-7 immortalized hypothalamic neurons and open new
      avenues about the use of this cell line for the study of HO modulation of GnRH
      secretion and reproduction.

PMID- 18706975
TI  - Emergence of a novel highly specific and catalytically efficient enzyme from a
      naturally promiscuous glutathione transferase.
AB  - Redesign of glutathione transferases (GSTs) has led to enzymes with remarkably
      enhanced catalytic properties. Exchange of substrate-binding residues in GST A1-1
      created a GST A4-4 mimic, called GIMFhelix, with >300-fold improved activity with
      nonenal and suppressed activity with other substrates. In the present
      investigation GIMFhelix was compared with the naturally-evolved GSTs A1-1 and A4
      4 by determining catalytic efficiencies with nine alternative substrates. The
      enzymes can be represented by vectors in multidimensional substrate-activity
      space, and the vectors of GIMFhelix and GST A1-1, expressed in kcat/Km values for
      the alternative substrates, are essentially orthogonal. By contrast, the vectors
      of GIMFhelix and GST A4-4 have approximately similar lengths and directions. The
      broad substrate acceptance of GST A1-1 contrasts with the high selectivity of GST
      A4-4 and GIMFhelix for alkenal substrates. Multivariate analysis demonstrated
      that among the diverse substrates used, nonenal, cumene hydroperoxide, and
      androstenedione are major determinants in the portrayal of the three enzyme
      variants. These GST substrates represent diverse chemistries of naturally
      occurring substrates undergoing Michael addition, hydroperoxide reduction, and
      steroid double-bond isomerization, respectively. In terms of function, GIMFhelix
      is a novel enzyme compared to its progenitor GST A1-1 in spite of 94% amino-acid
      sequence identity between the enzymes. The redesign of GST A1-1 into GIMFhelix
      therefore serves as an illustration of divergent evolution leading to novel
      enzymes by minor structural modifications in the active site. Notwithstanding low
      sequence identity (60%), GIMFhelix is functionally an isoenzyme of GST A4-4.

PMID- 18706977
TI  - Interaction assays in yeast and cultured cells confirm known and identify novel
      partners of the synaptic vesicle protein synaptophysin.
AB  - Synaptophysin (SYP) is a major protein of neurotransmitter-containing vesicles
      spanning the membrane four times and contributing to various aspects of the
      synaptic vesicle cycle. The split-ubiquitin yeast two-hybrid system was used to
      characterize molecular interactions of membrane-bound, full-length murine SYP. In
      this way, the known homophilic SYP-SYP association could be confirmed and
      heterophilic binding of SYP to other tetraspan vesicle membrane proteins of the
      secretory carrier-associated membrane- and synaptogyrin-type could be detected
      for the first time. SYP-binding was also observed for the vSNARE synaptobrevin2
      and various membrane and membrane-associated proteins. Double labeling
      immunofluorescence microscopy of murine retina, co-immunoprecipitation
      experiments and fluorescence energy resonance transfer (FRET) analyses between
      fluorescent protein-tagged polypeptides were carried out to validate and further
      characterize the association of SYP with the tetraspan vesicle membrane proteins
      secretory carrier-associated membrane protein 1 and synaptogyrin3, with
      synaptobrevin2, and the newly identified binding partners phospholipase D4,
      stathmin-like3, Rho family GTPase2 and ADP-ribosylation factor interacting
      protein2. It was observed that the carboxyterminus of SYP is dispensable for
      association with integral membrane proteins while it is needed for binding to
      membrane-associated polypeptides. The latter appears to be regulated by
      phosphorylation, since src homology 2-domains were shown to attach to the
      multiple carboxyterminal phosphotyrosine residues of SYP. In conclusion, the
      association of SYP with different tetraspan vesicle membrane proteins suggests
      shared functions and the multiple other interactions identify SYP as part of a
      membrane platform acting as a facilitator of various steps of the synaptic
      vesicle cycle.

PMID- 18706976
TI  - Studying chromosome instability in the mouse.
AB  - Aneuploidy has long been recognized as one of the hallmarks of cancer. It
      nonetheless remains uncertain whether aneuploidy occurring early in the
      development of a cancer is a primary cause of oncogenic transformation, or
      whether it is an epiphenomenon that arises from a general breakdown in cell cycle
      control late in tumorigenesis. The accuracy of chromosome segregation is ensured
      both by the intrinsic mechanics of mitosis and by an error-checking spindle
      assembly checkpoint. Many cancers show altered expression of proteins involved in
      the spindle checkpoint or in proteins implicated in other mitotic processes. To
      understand the role of aneuploidy in the initiation and progression of cancer, a
      number of spindle checkpoint genes have been disrupted in mice, most through
      conventional gene targeting (to create germ-line knockouts). We describe the
      consequence of these mutations with respect to embryonic development, tumor
      progression and an unexpected link to premature aging; readers are referred
      elsewhere [1] for a discussion of other cell cycle regulators.

PMID- 18706978
TI  - Cellular localization of metabotropic glutamate receptors in cortical tubers and
      subependymal giant cell tumors of tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder associated
      with cortical malformations (cortical tubers) and the development of glial tumors
      (subependymal giant-cell tumors, SGCTs). Expression of metabotropic glutamate
      receptor (mGluR) subtypes is developmentally regulated and several studies
      suggest an involvement of mGluR-mediated glutamate signaling in the regulation of
      proliferation and survival of neural stem-progenitor cells, as well as in the
      control of tumor growth. In the present study, we have investigated the
      expression and cell-specific distribution of group I (mGluR1, mGluR5), group II
      (mGluR2/3) and group III (mGluR4 and mGluR8) mGluR subtypes in human TSC
      specimens of both cortical tubers and SGCTs, using immunocytochemistry. Strong
      group I mGluR immunoreactivity (IR) was observed in the large majority of TSC
      specimens in dysplastic neurons and in giant cells within cortical tubers, as
      well as in tumor cells within SGCTs. In particular mGluR5 appeared to be most
      frequently expressed, whereas mGluR1alpha was detected in a subpopulation of
      neurons and giant cells. Cells expressing mGluR1alpha and mGluR5, demonstrate IR
      for phospho-S6 ribosomal protein (PS6), which is a marker of the mammalian target
      of rapamycin (mTOR) pathway activation. Group II and particularly group III mGluR
      IR was less frequently observed than group I mGluRs in dysplastic neurons and
      giant cells of tubers and tumor cells of SGCTs. Reactive astrocytes were mainly
      stained with mGluR5 and mGluR2/3. These findings expand our knowledge concerning
      the cellular phenotype in cortical tubers and in SGCTs and highlight the role of
      group I mGluRs as important mediators of glutamate signaling in TSC brain
      lesions. Individual mGluR subtypes may represent potential pharmacological
      targets for the treatment of the neurological manifestations associated with TSC
      brain lesions.

PMID- 18706979
TI  - Leucine-rich repeat-containing G-protein-coupled receptor 8 in the rat brain:
      Enrichment in thalamic neurons and their efferent projections.
AB  - Leucine-rich repeat-containing G-protein-coupled receptor 8 (LGR8; also
      classified as relaxin family peptide 2 receptor; RXFP2) has been identified as a
      cognate receptor for the peptide hormone, insulin-like peptide 3 (INSL3) and
      INSL3-LGR8 signaling plays an essential role in testis descent and germ cell
      development in human and rodents. Lgr8 mRNA has been detected in human tissues
      including testis, kidney and brain, but its regional and cellular distribution in
      these tissues in human or other species is largely unknown. In an initial step to
      elucidate the physiological function of a putative INSL3-LGR8 system in rat
      brain, the localization of Lgr8 mRNA was investigated using in situ hybridization
      histochemistry, revealing a discrete distribution in forebrain, with expression
      highly enriched in the thalamus. High densities were detected in the
      parafascicular nucleus (Pf), the dorsolateral, ventrolateral and posterior
      thalamic nuclei, and in the medial habenula. Lgr8 transcripts were also detected
      in frontal and motor cortices. The comparative distribution of LGR8 (receptor
      protein) was examined by autoradiography of [125I]-human INSL3 binding sites,
      with high densities detected in the thalamus, especially in Pf, and in the entire
      striatum--the caudate putamen (CPmicro), islands of Calleja, olfactory tubercle,
      nucleus accumbens--with lower levels in distinct layers of cerebral cortex.
      Notably, these areas also receive dopaminergic projections. These findings
      demonstrate the existence of LGR8 in neuronal soma in the thalamus and
      axons/terminals in thalamic target areas such as the striatum and frontal cortex.
      LGR8 was also detected throughout the medial habenula-fasciculus retroflexus
      interpeduncular nucleus pathway, further indicating that the receptor is
      transported from mRNA-expressing soma to remote axonal/terminal sites. These
      findings suggest the existence of a broadly distributed LGR8 signaling system in
      the rat involved in sensorimotor, limbic and cognitive functions. Further studies
      are now required to elucidate the precise function of LGR8, under normal and
      pathological conditions, as importantly, several of the equivalent receptor
      positive areas in human brain are part of the pathology of neurodegenerative
      conditions including Parkinson's disease.

PMID- 18706980
TI  - Enhanced glutamatergic phenotype of mesencephalic dopamine neurons after neonatal
      6-hydroxydopamine lesion.
AB  - There is increasing evidence that a subset of midbrain dopamine (DA) neurons uses
      glutamate as a co-transmitter and expresses vesicular glutamate transporter
      (VGLUT) 2, one of the three vesicular glutamate transporters. In the present
      study, double in situ hybridization was used to examine tyrosine hydroxylase (TH)
      and VGLUT2 mRNA expression during the embryonic development of these neurons, and
      postnatally, in normal rats and rats injected with 6-hydroxydopamine (6-OHDA) at
      P4 to destroy partially DA neurons. At embryonic days 15 and 16, there was a
      regional overlap in the labeling of TH and VGLUT2 mRNA in the ventral
      mesencephalon, which was no longer found at late embryonic stages (E18-E21) and
      postnatally. In normal pups from P5 to P15, only 1-2% of neurons containing TH
      mRNA in the ventral tegmental area (VTA) and substantia nigra, pars compacta,
      also displayed VGLUT2 mRNA. In contrast, after the cerebroventricular
      administration of 6-OHDA at P4, 26% of surviving DA neurons in the VTA of P15
      rats expressed VGLUT2. To search for a colocalization of TH and VGLUT2 protein in
      axon terminals of these neurons, the nucleus accumbens of normal and 6-OHDA
      lesioned P15 rats was examined by electron microscopy after dual
      immunocytochemical labeling. In normal rats, VGLUT2 protein was found in 28% of
      TH positive axon terminals in the core of nucleus accumbens. In 6-OHDA-lesioned
      rats, the total number of TH positive terminals was considerably reduced, and yet
      the proportion also displaying VGLUT2 immunoreactivity was modestly but
      significantly increased (37%). These results lead to the suggestion that the
      glutamatergic phenotype of a VTA DA neurons is highly plastic, repressed toward
      the end of normal embryonic development, and derepressed postnatally following
      injury. They also support the hypothesis of co-release of glutamate and DA by
      mesencephalic neurons in vivo, at least in the developing brain.

PMID- 18706981
TI  - Effects of the transient receptor potential vanilloid 1 antagonist A-425619 on
      body temperature and thermoregulation in the rat.
AB  - Transient receptor potential vanilloid 1 (TRPV1) receptor antagonists have gained
      much attention for their potential to treat inflammatory and neuropathic pain.
      However, systemic administration of TRPV1 antagonists induces a period of
      hyperthermia, a potential liability for small molecule development. Here we
      characterize the effects of the TRPV1 antagonist A-425619 on body temperature
      (T(b)) in the rat when administered: (1) alone at different times of the
      circadian cycle, (2) as repeated hourly or daily treatment, (3) as pre-treatment
      to prevent capsaicin-induced hypothermia, (4) to capsaicin-desensitized animals,
      and (5) prior to a heat challenge. Changes in T(b) were compared with compound
      exposure data, locomotor activity, and time course of efficacy in inflammatory
      pain models. Without affecting locomotor activity, oral administration of A
      425619 induced a transient period of hyperthermia that was followed by a period
      of hypothermia, a profile unique among reported TRPV1 antagonists. Repeated
      hourly administration of A-425619 produced an increase in T(b) similar to a
      single administration. A-425619 had no effect on T(b) when administered to
      capsaicin-desensitized rats. The duration of A-425619-induced hyperthermia, but
      not hypothermia, was dependent on the time of the circadian cycle when
      administered. Pre-treatment with A-425619 attenuated capsaicin-induced
      hypothermia and did not potentiate T(b) or alter thermoregulatory behavioral
      responses during a heat challenge. These results indicate that A-425619-induced
      hyperthermia is transient, circadian-dependent, not related to exposure levels,
      locomotor activity, or time course of analgesic action, and does not affect the
      ability to thermoregulate during a heat challenge.

PMID- 18706982
TI  - Systemic infection and inflammation in acute CNS injury and chronic
      neurodegeneration: underlying mechanisms.
AB  - We have all at some time experienced the non-specific symptoms that arise from
      being ill following a systemic infection. These symptoms, such as fever, malaise,
      lethargy and loss of appetite are often referred to as "sickness behavior" and
      are a consequence of systemically produced pro-inflammatory mediators. These
      inflammatory mediators signal to the brain, leading to activation of microglial
      cells, which in turn, signal to neurons to induce adaptive metabolic and
      behavioral changes. In normal healthy persons this response is a normal part of
      our defense, to protect us from infection, to maintain homeostasis and causes no
      damage to neurons. However, in animals and patients with chronic
      neurodegenerative disease, multiple sclerosis, stroke and even during normal
      aging, systemic inflammation leads to inflammatory responses in the brain, an
      exaggeration of clinical symptoms and increased neuronal death. These
      observations imply that, as the population ages and the number of individuals
      with CNS disorders increases, relatively common systemic infections and
      inflammation will become significant risk factors for disease onset or
      progression. In this review we discuss the underlying mechanisms responsible for
      sickness behavior induced by systemic inflammation in the healthy brain and how
      they might be different in individuals with CNS pathology.

PMID- 18706983
TI  - The origin of genes could be polyphyletic.
AB  - The paradigm of the monophyletic origin of genes is deeply rooted in us all. For
      instance, this stems from the observation that the possibility of obtaining a
      good multiple alignment using the same protein from organisms from the three
      domains of life (Bacteria, Archaea and Eukarya) would seem to imply that the last
      universal common ancestor (LUCA) must have had that protein and, therefore, the
      origin of that gene must necessarily be monophyletic. The hypothesis of a
      polyphyletic origin of genes has to explain how it was possible to evolve highly
      conserved regions of multiple alignments of orthologous proteins from the three
      domains of life when these regions clearly seem to define a monophyletic origin
      of genes. If mRNAs were assembled at the stage of the LUCA through the trans
      splicing of pieces of RNA representing mini-genes, and the translation of these
      mRNAs resulted in proteins whose genes (DNA) actually only evolved much later,
      i.e. only after the main domains of life were established, then this would
      explain why multiple alignments of orthologous proteins can be obtained from the
      three domains of life. Therefore, this makes these multiple alignments compatible
      with a polyphyletic origin of genes. I have analysed many multiple alignments of
      orthologous proteins from the three domains of life, reaching a conclusion that
      seems to suggest that these alignments are also compatible with a polyphyletic
      origin of genes because, for instance, they contain protein motifs characterising
      the domains of life. These motifs, and also genes, might have evolved late on,
      thus making their polyphyletic origin likely.

PMID- 18706984
TI  - Cold acclimation-induced up-regulation of the ribosomal protein L7 gene in the
      freeze tolerant wood frog, Rana sylvatica.
AB  - Natural freezing survival by the wood frog, Rana sylvatica, involves multiple
      organ-specific changes in gene expression. The present study used differential
      display PCR to find cold-responsive genes in wood frog skin. A cDNA was retrieved
      from skin that was in higher amounts in cold- versus warm-acclimated frogs. The
      cDNA was used to probe a wood frog liver cDNA library and retrieve a long
      sequence that, after the further application of 5'RACE, was shown to encode the
      full sequence of the ribosomal large subunit protein 7 (RPL7) (GenBank accession
      number AF175983). Wood frog RPL7 contained 246 amino acids and shared 90%
      identity with Xenopus laevis RPL7, 82-83% with chicken and zebrafish homologues,
      and 79% with mammalian RPL7. Multiple binding domains found in human RPL7 showed
      differing degrees of conservation in the frog protein. Transcript levels of rpl7
      were elevated up to 4-fold in skin of cold-acclimated frogs as compared with warm
      acclimated animals. Organ-specific responses by rpl7 transcripts also occurred
      when frogs were given survivable freezing exposures. Transcripts rose by 1.8-3.3
      fold in brain and skeletal muscle during freezing but were unaffected in central
      organs such as liver and heart. Up-regulation of rpl7 also occurred in brain of
      anoxia-exposed frogs and RPL7 protein levels increased strongly in heart under
      both freezing and dehydration stresses. Cold- and freezing-responsive up
      regulation of the rpl7 gene and RPL7 protein in selected organs suggests that
      targeted changes in selected ribosomal proteins may be an integral part of
      natural freeze tolerance.

PMID- 18706985
TI  - Comparing single and repeated dosimetry data for perfluorooctane sulfonate in
      rats.
AB  - Perfluorooctane sulfonate (PFOS) is a member of a class of perfluorinated
      chemicals used in a variety of consumer and industrial applications because of
      their oleophobic and hydrophobic properties. It has been shown to cause toxicity
      in adult and developing laboratory animals. Because PFOS has also been shown to
      be widely distributed throughout the environment, there have been concerns about
      its potential health risk to humans. Limited pharmacokinetic data for PFOS are
      available in rodents and humans, while epidemiological studies of workers and
      extensive toxicity studies in rodents have been performed. The existing
      pharmacokinetic and toxicity database in rodents can be useful in the cross
      species extrapolations needed to evaluate and interpret internal dosimetry in
      humans. A mathematical model that describes the disposition of PFOS in adult rats
      following intravenous, oral, and chronic dietary exposures was developed to gain
      a better understanding of the pharmacokinetics of PFOS and to determine whether
      single-dose kinetics are predictive of repeated-dose kinetics. In order to
      characterize existing time-course data, time-dependent and concentration
      dependent changes in the pharmacokinetic parameters for urinary and biliary
      clearance and liver distribution were needed. Whether these time-dependent
      changes represent inconsistencies across experiments, effects of aging in the
      rats, or chemically induced changes in pharmacokinetics remains to be determined.

PMID- 18706986
TI  - Acute effects of 1-octen-3-ol, a microbial volatile organic compound (MVOC)--an
      experimental study.
AB  - Acute effects were assessed from exposure to a common volatile compound of
      microbial origin, the aliphatic alcohol 1-octen 3-ol (octenol). Twenty-nine
      volunteers performed symptom reports, measurement of blink frequency by
      electromyography, measurement of the eye break-up time, vital staining of the
      eye, nasal lavage, acoustic rhinometry, transfer tests and dynamic spirometry.
      Subjects were during 2h in random order exposed to either 10mg/m(3) of octenol or
      clean air as control. During octenol exposure subjective ratings of smell and
      nasal irritation were increased together with higher nasal lavage biomarker
      levels of eosinophil cationic protein, myeloperoxidase and lysozyme. Also eye
      irritation and blinking frequency were increased together with throat irritation,
      mild dyspnoea after 1-h but not after 2-h, and a small decrease in vital
      capacity. Ratings of headache and nausea were also increased. Atopics did not
      have more reactions due to exposure, whereas females experienced more smell and
      mucosal irritation. Thus, there were both subjective and objective signs of mild
      mucosal irritation of eyes and airways together with symptoms of headache and
      nausea.

PMID- 18706987
TI  - A controlled-release ocular delivery system for ibuprofen based on nanostructured
      lipid carriers.
AB  - The objective of this study was to develop an ocular drug delivery system based
      on nanostructured lipid carrier and investigate its in vitro and in vivo
      characteristics. Ibuprofen was chosen as the model drug. Four different
      formulations of ibuprofen nanostructured lipid carriers were prepared by melted
      ultrasonic methods; gelucire 44/14 was screened as one of the solid lipid matrix
      materials due to the good particle size dispersion and excellent contribution to
      the corneal permeability of the model drug. The modified Franz-type diffusion
      cells and isolated corneas were used in the test of drug corneal permeability and
      the in vivo releasing tests were carried out using microdialysis method. gelucire
      44/14 and transcutol P could enhance the corneal permeability by different
      mechanisms. The corresponding apparent permeability coefficients (P(app)) were
      1.28 and 1.36 times more than that of the control preparation. Stearylamine could
      prolong the pre-cornea retention time of the model drug to some extent. Ibuprofen
      nanostructured lipid carriers displayed controlled-release property. The AUC of
      the optimized formulation of ibuprofen nanostuctured lipid carriers was 3.99
      times more than that of ibuprofen eye drops).

PMID- 18706988
TI  - Microencapsulation by solvent evaporation: state of the art for process
      engineering approaches.
AB  - Microencapsulation by solvent evaporation technique is widely used in
      pharmaceutical industries. It facilitates a controlled release of a drug, which
      has many clinical benefits. Water insoluble polymers are used as encapsulation
      matrix using this technique. Biodegradable polymer PLGA (poly(lactic-co-glycolic
      acid)) is frequently used as encapsulation material. Different kinds of drugs
      have been successfully encapsulation: for example hydrophobic drugs such as
      cisplatin, lidocaine, naltrexone and progesterone; and hydrophilic drugs such as
      insulin, proteins, peptide and vaccine. The choice of encapsulation materials and
      the testing of the release of drug have been intensively investigated. However
      process-engineering aspects of this technique remain poorly reported. To succeed
      in the controlled manufacturing of microspheres, it is important to investigate
      the latter. This article reviews the current state of the art concerning this
      technique by focusing on the influence of the physical properties of materials
      and operating conditions on the microspheres obtained. Based on the existing
      results and authors' reflection, it gives rise to reasoning and suggested choices
      of materials and process conditions. A part of this paper is also dedicated to
      numerical models on the solvent evaporation and the solidification of
      microspheres. This review reveals also the surprising lack of knowledge on
      certain aspects, such as the mechanism of formation of pores in the microspheres
      and the experimental study on the solidification of microspheres.

PMID- 18706989
TI  - Physicochemical and pharmacokinetic characterization of water-soluble Coenzyme
      Q(10) formulations.
AB  - Coenzyme Q(10) (CoQ(10)) has been used as a drug for chronic heart failure.
      Furthermore, various biological effects of CoQ(10) have also been applied for
      food supplements and cosmetics. However, CoQ(10) was found to be poorly soluble
      in water, so that its bioavailability was low and variable depending on food
      intake. In the present investigation, a novel liquid (nano-emulsion, NE) and
      water-soluble powder formulations, including cyclodextrin-Q10 complex (CoQ(10)
      CD) and dry-emulsion (DE), were prepared. The physicochemical properties of each
      formulation were characterized by dynamic light scattering (DLS), scanning
      electron microscopy (SEM), powder X-ray diffractometry (PXRD), and differential
      scanning calorimetry (DSC). In all powder formulations prepared, CoQ(10) existed
      mainly as an amorphous form as determined by PXRD and DSC, and each powder
      formulation exhibited high solubility and dispersibility in water resulting in
      the formation of a nano-sized emulsion (NE; 60nm) and micron sized particles (DEs
      and CoQ(10)-CD; 0.77-2.4microm). The pharmacokinetic study of each dosage form,
      in comparison to a CoQ(10) crystal suspension, was also carried out in rats after
      a single oral dose. Although similar kinetic values were seen with T(max) of 1.5
      and 1.7h, respectively, for NE and crystalline CoQ(10), NE exhibited ca 1.7-fold
      higher AUC and C(max) than the crystalline CoQ(10).

PMID- 18706990
TI  - Poisonous plants of veterinary and human importance in southern Africa.
AB  - Southern Africa is inherently rich in flora, where the habitat and climatic
      conditions range from arid environments to lush, sub-tropical greenery. Needless
      to say, with such diversity in plant life there are numerous indigenous poisonous
      plants, and when naturalised exotic species and toxic garden varieties are added
      the list of potential poisonous plants increases. The economically important
      poisonous plants affecting livestock and other plant poisonings of veterinary
      significance are briefly reviewed. In addition, a synopsis of the more common
      plant poisonings in humans is presented. Many of the plants mentioned in this
      review are also used ethnobotanically for treatment of disease in humans and
      animals and it is essential to be mindful of their toxic potential.

PMID- 18706991
TI  - Prediction of autistic disorder using neuro fuzzy system by applying ANN
      technique.
AB  - The major challenge in medical field is to diagnose disorder rather than a
      disease. In this paper, a neuro fuzzy based model is designed for identification
      or diagnosis of autism. The problematic areas are gathered from every individual
      and the related linguistic inputs are converted into fuzzy input values which are
      in turn given as input to feed forward multilayer neural network. The network is
      trained using back propagation training algorithm and tested for its performance
      with the expertise.

PMID- 18706992
TI  - Gossypol repressed the gap junctional intercellular communication between Sertoli
      cells by decreasing the expression of Connexin43.
AB  - Previous studies showed that gossypol could block the gap junctional
      intercellular communication (GJIC) between cultured cells. The present study was
      designed to investigate the effects of gossypol on the GJIC and the expression of
      connexin43 (Cx43) in the cultured cells. A Sertoli cell line, TM4, was treated
      with different concentrations of gossypol 1.25, 2.5, 5, and 10micromol/L for 6,
      12, 24, and 48h. Cell viability was assessed with CCK-8 assay. GJIC in the cells
      was determined using the scrape loading and dye transfer (SLDT) assay; the
      expression of Cx43 was detected by RT-PCR, immunofluorescence and Western blot
      analysis. The SLDT assay showed gossypol significantly decreased GJIC between
      adjacent cells. RT-PCR, immunofluorescence and Western blot analyses demonstrated
      the expression of Cx43 in TM4 cells. The expression of Cx43 was gradually
      decreased with the increasing concentrations of gossypol, and the effect occurred
      as early as 6h after the treatment and continued until 48h. These results
      suggested that gossypol impaired GJIC by decrease of Cx43 expression in the
      cells, which is important for Sertoli cells to regulate spermatogenesis.

PMID- 18706993
TI  - Detection of autoantibodies to neural cells of the cerebellum in the plasma of
      subjects with autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) are a group of heterogeneous, behaviorally
      defined disorders characterized by disturbances in social interaction and
      communication, often with repetitive and stereotyped behavior. Previous studies
      have described the presence of antibodies to various neural proteins in autistic
      individuals as well as post-mortem evidence of neuropathology in the cerebellum.
      We examined plasma from children with ASD, as well as age-matched typically
      developing controls, for antibodies directed against human cerebellar protein
      extracts using Western blot analysis. In addition, the presence of cerebellar
      specific antibodies was assessed by immunohistochemical staining of sections from
      Macaca fascicularis monkey cerebellum. Western blot analysis revealed that 13/63
      (21%) of subjects with ASD possessed antibodies that demonstrated specific
      reactivity to a cerebellar protein with an apparent molecular weight of
      approximately 52 kDa compared with only 1/63 (2%) of the typically developing
      controls (p=0.0010). Intense immunoreactivity, to what was determined
      morphologically to be the Golgi cell of the cerebellum, was noted for 7/34 (21%)
      of subjects with ASD, compared with 0/23 of the typically developing controls.
      Furthermore, there was a strong association between the presence of antibodies
      reactive to the 52 kDa protein by Western blot with positive immunohistochemical
      staining of cerebellar Golgi cells in the ASD group (r=0.76; p=0.001) but not
      controls. These studies suggest that when compared with age-matched typically
      developing controls, children with ASD exhibit a differential antibody response
      to specific cells located in the cerebellum and this response may be associated
      with a protein of approximately 52 kDa.

PMID- 18706995
TI  - Correlation of serum anti-Mullerian hormone with accelerated follicle loss
      following 4-vinylcyclohexene diepoxide-induced follicle loss in mice.
AB  - A chemically induced model of ovarian failure has been developed in rodents, and
      was used to test whether or not anti-Mullerian hormone (AMH) can be used as a non
      invasive measure of primordial follicle numbers. Repeated exposures of mice to 4
      vinylcyclohexene diepoxide (VCD) induce loss of primordial and earliest growing
      ovarian follicles. An accelerated exposure regimen was used to eliminate small
      ovarian follicles in C57BL6/J mice (240mg VCD/kg/day, 5 days, i.p.). Follicle
      populations were determined and correlated with circulating AMH levels. Exposures
      decreased only primordial and small primary follicles by 96% on day 16 after
      initiating exposures, followed by almost complete follicle elimination on days 37
      100. AMH levels in VCD-exposed mice were similar to vehicle-treated mice on day
      16, but became significantly lower or undetectable at later time points. Thus,
      AMH correlated well with growing follicle numbers. AMH only correlated with
      primordial follicles at time points after ovarian insult at which their loss led
      to decreased growing follicle numbers.

PMID- 18706994
TI  - Minocycline suppresses morphine-induced respiratory depression, suppresses
      morphine-induced reward, and enhances systemic morphine-induced analgesia.
AB  - Recent data suggest that opioids can activate immune-like cells of the central
      nervous system (glia). This opioid-induced glial activation is associated with
      decreased analgesia, owing to the release of proinflammatory mediators. Here, we
      examine in rats whether the putative microglial inhibitor, minocycline, may
      affect morphine-induced respiratory depression and/or morphine-induced reward
      (conditioned place preference). Systemic co-administration of minocycline
      significantly attenuated morphine-induced reductions in tidal volume, minute
      volume, inspiratory force, and expiratory force, but did not affect morphine
      induced reductions in respiratory rate. Minocycline attenuation of respiratory
      depression was also paralleled with significant attenuation by minocycline of
      morphine-induced reductions in blood oxygen saturation. Minocycline also
      attenuated morphine conditioned place preference. Minocycline did not simply
      reduce all actions of morphine, as morphine analgesia was significantly
      potentiated by minocycline co-administration. Lastly, morphine dose-dependently
      increased cyclooxygenase-1 gene expression in a rat microglial cell line, an
      effect that was dose-dependently blocked by minocycline. Together, these data
      support that morphine can directly activate microglia in a minocycline
      suppressible manner and suggest a pivotal role for minocycline-sensitive
      processes in the mechanisms of morphine-induced respiration depression, reward,
      and pain modulation.

PMID- 18706996
TI  - Diisobutyl phthalate impairs the androgen-dependent reproductive development of
      the male rat.
AB  - Diisobutyl phthalate (DIBP) is the branched isomer of DBP; DBP side chains have a
      four-carbon backbone (C4), whereas DIBP has its four-carbon alkyl side chains
      rearranged into a three-carbon backbone (C3) with a methyl branch. Di-n-butyl
      phthalate (DBP), and several other ortho-phthalate esters with side-chain lengths
      of C4-C6, are known to disrupt the androgen-dependent sexual differentiation in
      the male rat. This study was performed to determine whether in utero exposure to
      DIBP would induce permanent and dose-responsive alterations of male reproductive
      development. Pregnant Sprague-Dawley rats were administered olive oil (vehicle
      control), DIBP or DBP, by gavage on gestation Days 12-21, at doses of 125, 250,
      500, 625mgDIBP/(kg day) and 500mgDBP/(kg day). DIBP caused no overt maternal
      toxicity, nor reduced litter size. Male offspring displayed reduced neonatal
      anogenital distance (Postnatal day 1, PND) at 250mgDIBP/(kg day) and higher
      doses, and dose-related retention of areolas/nipples (PND 12-14). Preputial
      separation (onset of puberty) was delayed in male offspring at 500 and
      625mgDIBP/(kg day). Hypospadias, cleft prepuce, and undescended testis were
      observed in males (11-12 or 16-17 weeks old) exposed in utero to 500 and
      625mgDIBP/(kg day). Histopathological lesions were also present in adult testes,
      mainly consisting in seminiferous tubule degeneration. Our results show that DIBP
      can cause severe and specific adverse effects on the male rat reproductive
      development, with a pattern similar to that of DBP. However, DIBP appeared
      slightly less potent than DBP in inducing malformations.

PMID- 18706998
TI  - Presystemic elimination of budesonide in man when administered locally at
      different levels in the gut, with and without local inhibition by ketoconazole.
AB  - The CYP3A4 substrate budesonide was used to investigate gut wall first-pass
      metabolism in jejunum, ileum and colon of eight healthy men. Three milligram
      budesonide in solution was installed at each location by intubation, with or
      without immediate prior local administration of 16mg ketoconazole.
      Simultaneously, deuterium-labelled budesonide (0.2mg) was administered
      intravenously. Pharmacokinetics of unlabelled and labelled budesonide in plasma
      was evaluated using LC-MS/MS. Ketoconazole increased budesonide systemic
      availability significantly in jejunum (from 11.8 to 21.7%) and ileum (from 15.9
      to 31.8%). T(max) and MAT were unaffected. No significant effects were noted
      after colon administrations, nor were there any effects on the pharmacokinetics
      of intravenously administered budesonide. The increased bioavailability is most
      probably explained as inhibition of gut wall metabolism. The data are in
      accordance with the well-known CYP3A activity in the small intestine, evidently
      capable of metabolising at least half the absorbed dose of budesonide. In
      contrast, the results indicate that this enzyme activity is insignificant in the
      colon.

PMID- 18706997
TI  - Effects of methylmercury on postnatal neurobehavioral development in mice.
AB  - Eighty ICR mice were randomly assigned to one of four groups given daily
      intraperitoneal injections of 0, 0.1, 1 or 3 mg/kg MeHg chloride respectively
      from postnatal days (PD) 15-17, and then tested with the Morris water maze on
      PD45. After that the mice were sacrificed by cervical dislocation, and the
      protein levels of NMDA receptor subtypes in the hippocampus were measured by
      Western blot analysis. A significant increase in the latency (F=2.88, P<0.05)
      before finding the platform was observed in the 1 and 3 mg/kg MeHg exposure
      groups. Further, the 3 mg/kg MeHg exposure group also had a longer swim distance
      (F=2.97, P<0.05) for finding the platform. In the probe test, the MeHg exposure
      groups displayed a smaller number of platform crossings when the hidden platform
      was moved, but this did not reach statistical significance. Western blot analysis
      results showed significant increases in the levels of NR1, NR2A and NR2B proteins
      of the hippocampus in the 1 and 3 mg/kg MeHg exposure groups. Overall, the
      current study found that MeHg exposure at 1 and 3 mg/kg doses during the
      postnatal brain growth spurt induces subtle and persistent learning deficits, and
      the neurobehavioral abnormalities of MeHg-exposed mice might be ascribed to
      alteration of the gene expression of specific NMDA receptor subunits in the
      hippocampus.

PMID- 18706999
TI  - Disease-associated carbohydrate-recognising proteins and structure-based
      inhibitor design.
AB  - The role of carbohydrate-related pathways in a wide range of clinically
      significant diseases has provided great impetus for researchers to characterise
      key proteins as targets for drug discovery. Carbohydrate-recognising proteins
      essential in the lifecycles of high health impact pathogens and diseases such as
      diabetes, cancer, autoimmunity, inflammation and in-born errors of metabolism
      continue to stimulate much interest in both structure elucidation and structure
      based drug design. For example, advances in structure-based inhibitor design
      against the mycobacterial enzyme UDP-galactopyranose mutase offer new hope in
      next generation anti-tuberculosis chemotherapeutics. The appearance of H5N1 avian
      influenza virus has re-stimulated much research on influenza virus haemagglutinin
      and sialidase. These latest developments on influenza virus sialidase have
      provided new opportunity for the development of Group 1-specific anti-influenza
      drugs. The role of siglecs and galectins in a range of disease processes such as
      inflammation, apoptosis and cancer progression has also inspired significant
      structure-based inhibitor design research.

PMID- 18707000
TI  - The insecticidal activity of recombinant garlic lectins towards aphids.
AB  - The heterodimeric and homodimeric garlic lectins ASAI and ASAII were produced as
      recombinant proteins in the yeast Pichia pastoris. The proteins were purified as
      functional dimeric lectins, but underwent post-translational proteolysis.
      Recombinant ASAII was a single homogenous polypeptide which had undergone C
      terminal processing similar to that occurring in planta. The recombinant ASAI was
      glycosylated and subject to variable and heterogenous proteolysis. Both lectins
      showed insecticidal effects when fed to pea aphids (Acyrthosiphon pisum) in
      artificial diet, ASAII being more toxic than ASAI at the same concentration.
      Acute toxicity (mortality at < or =48 h exposure; similar timescale to
      starvation) was only apparent at the highest lectin concentrations tested (2.0 mg
      ml(-)1), but dose-dependent chronic toxicity (mortality at >3d exposure) was
      observed over the concentration range 0.125-2.0 mg ml(-1). The recombinant
      lectins caused mortality in both symbiotic and antibiotic-treated aphids, showing
      that toxicity is not dependent on the presence of the bacterial symbiont
      (Buchnera aphidicola), or on interaction with symbiont proteins, such as the
      previously identified lectin "receptor" symbionin. A pull-down assay coupled with
      peptide mass fingerprinting identified two abundant membrane-associated aphid gut
      proteins, alanyl aminopeptidase N and sucrase, as "receptors" for lectin binding.

PMID- 18707001
TI  - Effect of hypomagnesemia on allogeneic activation in mice.
AB  - INTRODUCTION: Magnesium (Mg) plays an essential role in a wide range of
      fundamental cellular reactions. It has been reported that in rodents Mg-deficient
      diet-induced hypomagnesemia results in an early inflammation. We have previously
      shown that chronic severe hypomagnesemia was associated neither with endothelial
      cell activation nor with an inflammatory process which are crucial in the
      allograft rejection process. T cell allogeneic stimulation activates the
      phosphatase calcineurin which triggers the signaling pathways leading to IL-2
      synthesis and lymphocyte proliferation. Full activation of calcineurin requires
      Mg. Surveys suggest that a significant number of people consume less Mg than the
      international dietary reference intakes leading to hypomagnesemia in 2.5% to 15%
      of the general population. OBJECTIVE: The aim of the study was to investigate the
      effects of hypomagnesemia on lymphocyte allogeneic activation and proliferation
      in a murine model of dietary-induced hypomagnesemia. METHODS: C57BL/6J (H-2(b),
      Mls(b)) mice were given normal Mg-containing diet (1400 ppm Mg, control mice), or
      synthetic Mg-deficient diets containing either 50 ppm Mg or 150 ppm Mg for 28
      days. Serum Mg levels were determined at days 5, 14 and 28. In parallel, complete
      urine and faeces were collected by using metabolic cages during a 24 h period for
      Mg determinations. Splenocytes from C57BL/6 mice fed either normal diet or 50 ppm
      Mg-diet were used as responder cells in mixed lymphocyte reaction (MLR) performed
      with splenocytes from C3H/He mice (H-2(k), Mls(IIa)) and C57BL/6 mice fed normal
      diet as stimulators for allogeneic and isogeneic conditions, respectively. TGF
      beta and IL-2 productions were quantified in the supernates of mixed splenocytes
      cultures. 3x10(6) splenocytes from mice fed 50 ppm Mg-diet were used for
      calcineurin activity determination at day 28. RESULTS: In mice fed 150 ppm Mg
      diet, moderate hypomagnesemia was observed from day 5 to day 28. Oral
      supplementation with Mg pidolate (5 or 20 mg Mg/kg/day) could not restore normal
      serum Mg levels. Serum Mg concentration early decreased in mice fed 50 ppm Mg
      diet to achieve stabilized severe hypomagnesemia at days 14 and 28. Urine Mg
      concentration early dramatically fell down then stabilized in mice fed Mg
      deficient diets. In MLR performed at day 28 with splenocytes from mice fed 50 ppm
      Mg-diet, proliferation and IL-2 production in allogeneic conditions were similar
      to control mice. No TGF-beta production was detected in any group. Lastly,
      calcineurin activity measured at day 28 was significantly lower in splenocyes
      from mice fed 50 ppm Mg-diet than in mice fed control diet. CONCLUSION: Mg
      deficiency does not alter splenocyte allogeneic activation and proliferation and
      IL-2 production in vitro, although it partially inhibits calcineurin activity. We
      hypothesize that the remaining activity is sufficient for IL-2 gene normal
      activation. Alternatively, Mg-deficiency may trigger other signaling pathways
      leading to IL-2 production.

PMID- 18707002
TI  - Short- and long-term limbic abnormalities after experimental febrile seizures.
AB  - Experimental febrile seizures (FS) are known to promote hyperexcitability of the
      limbic system and increase the risk for eventual temporal lobe epilepsy (TLE).
      Early markers of accompanying microstructural and metabolic changes may be
      provided by in vivo serial MRI. FS were induced in 9-day old rats by
      hyperthermia. Quantitative multimodal MRI was applied 24 h and 8 weeks later, in
      rats with FS and age-matched controls, and comprised hippocampal volumetry and
      proton spectroscopy, and cerebral T2 relaxometry and diffusion tensor imaging
      (DTI). At 9 weeks histology was performed. Hippocampal T2 relaxation time
      elevations appeared to be transient. DTI abnormalities detected in the amygdala
      persisted up to 8 weeks. Hippocampal volumes were not affected. Histology showed
      increased fiber density and anisotropy in the hippocampus, and reduced neuronal
      surface area in the amygdala. Quantitative serial MRI is able to detect
      transient, and most importantly, long-term FS-induced changes that reflect
      microstructural alterations.

PMID- 18707003
TI  - Pituitary adenylate cyclase-activating polypeptide stimulates glial fibrillary
      acidic protein gene expression in cortical precursor cells by activating Ras and
      Rap1.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) acts on cortical
      precursor cells to trigger glial fibrillary acidic protein (GFAP) gene expression
      and astrocyte differentiation by stimulation of intracellular cAMP production.
      Here, we show that as expected, PACAP activates cAMP-dependent protein kinase A.
      However, inhibition of protein kinase A does not prevent PACAP-induced GFAP gene
      expression or astrocytogenesis. PACAP also activates the small GTPases Rap1 and
      Ras, but either activation of Rap1 alone by selective stimulation of the guanine
      nucleotide exchange factor Epac, or expression of a constitutively active form of
      Ras, do not induce GFAP gene expression. Ras is activated by PACAP in a cAMP
      dependent manner, and inhibition of Ras and/or Rap1 decreases PACAP-induced GFAP
      promoter stimulation. Thus, cAMP-dependent PACAP-induced GFAP expression during
      astrocytogenesis involves the coordinated activation of both Ras and Rap1, but
      activation of either one of them in isolation is not sufficient to trigger this
      response.

PMID- 18707005
TI  - Characterisation of cDNAs of key genes involved in apoptosis in common carp
      (Cyprinus carpio L.).
AB  - Apoptosis is a morphologically and biochemically distinct form of eukaryotic cell
      death that occurs under a variety of physiological and pathological conditions.
      Many of the cell deaths that occur during normal embryological development and
      during normal tissue turnover display the morphological hallmarks of apoptosis.
      In the last 20 or so years a better biochemical picture of how the process occurs
      has been produced, at least in higher vertebrates. It is now widely accepted that
      many of the proteolytic cleavages occurring during apoptosis are mediated by
      caspases, the activation of which, in turn, has been found to be tightly
      regulated. The current study focuses on the sequencing and analysis of key genes
      involved in the apoptotic process, based on sequence similarity to known
      apoptosis genes from genetic models such as zebrafish (Danio rerio) and other
      vertebrates. The present study identifies key components of the apoptotic process
      in common carp (Cyprinus carpio L.), which in turn can be used, for example, to
      monitor the fate of the cellular components of the immune system after an immune
      challenge.

PMID- 18707004
TI  - Streptavidin crystals as nanostructured supports and image-calibration references
      for cryo-EM data collection.
AB  - For cryo-EM structural studies, we seek to image membrane proteins as single
      particles embedded in proteoliposomes. One technical difficulty has been the low
      density of liposomes that can be trapped in the approximately 100nm ice layer
      that spans holes in the perforated carbon support film of EM grids. Inspired by
      the use of two-dimensional (2D) streptavidin crystals as an affinity surface for
      biotinylated DNA (Crucifix et al., 2004), we propose to use the crystals to
      tether liposomes doped with biotinylated lipids. The 2D crystal image also serves
      as a calibration of the image formation process, providing an absolute conversion
      from electrostatic potentials in the specimen to the EM image intensity, and
      serving as a quality control of acquired cryo-EM images. We were able to grow
      streptavidin crystals covering more than 90% of the holes in an EM grid, and
      which remained stable even under negative stain. The liposome density in the
      resulting cryo-EM sample was uniform and high due to the high-affinity binding of
      biotin to streptavidin. Using computational methods, the 2D crystal background
      can be removed from images without noticeable effect on image properties.

PMID- 18707006
TI  - Measuring directional coupling between EEG sources.
AB  - Directional connectivity in the brain has been typically computed between scalp
      electroencephalographic (EEG) signals, neglecting the fact that correlations
      between scalp measurements are partly caused by electrical conduction through the
      head volume. Although recently proposed techniques are able to identify causality
      relationships between EEG sources rather than between recording sites, most of
      them need a priori assumptions about the cerebral regions involved in the EEG
      generation. We present a novel methodology based on multivariate autoregressive
      (MVAR) modeling and Independent Component Analysis (ICA) able to determine the
      temporal activation of the intracerebral EEG sources as well as their approximate
      locations. The direction of synaptic flow between these EEG sources is then
      estimated using the directed transfer function (DTF), and the significance of
      directional coupling strength evaluated with surrogated data. The reliability of
      this approach was assessed with simulations manipulating the number of data
      samples, the depth and orientation of the equivalent source dipoles, the presence
      of different noise sources, and the violation of the non-Gaussianity assumption
      inherent to the proposed technique. The simulations showed the superior accuracy
      of the proposed approach over other traditional techniques in most tested
      scenarios. Its validity was also evaluated analyzing the generation mechanisms of
      the EEG-alpha rhythm recorded from 20 volunteers under resting conditions.
      Results suggested that the major generation mechanism underlying EEG-alpha
      oscillations consists of a strong bidirectional feedback between thalamus and
      cuneus. The precuneus also seemed to actively participate in the generation of
      the alpha rhythm although it did not exert a significant causal influence neither
      on the thalamus nor on the cuneus. All together, these results suggest that the
      proposed methodology is a promising non-invasive approach for studying
      directional coupling between mutually interconnected neural populations.

PMID- 18707007
TI  - Image derived input functions for dynamic High Resolution Research Tomograph PET
      brain studies.
AB  - The High Resolution Research Tomograph (HRRT) is a dedicated human brain positron
      emission tomography (PET) scanner. The aim of the present study was to validate
      the use of image derived input functions (IDIF) as an alternative for arterial
      sampling for HRRT human brain studies. To this end, IDIFs were extracted from 3D
      ordinary Poisson ordered subsets expectation maximization (OP-OSEM) and
      reconstruction based partial volume corrected (PVC) OP-OSEM images. IDIFs, either
      derived directly from regions of interest or further calibrated using manual
      samples taken during scans, were evaluated for dynamic [(11)C]flumazenil data
      (n=6). Results obtained with IDIFs were compared with those obtained using blood
      sampler input functions (BSIF). These comparisons included areas under the curve
      (AUC) for peak (0-3.3 min) and tail (3.3-55.0 min). In addition, slope, intercept
      and Pearson's correlation coefficient of tracer kinetic analysis results based on
      IDIF and BSIF were calculated for each subject. Good peak AUC ratios (0.83+/
      0.21) between IDIF and BSIF were found for calibrated IDIFs extracted from OP
      OSEM images. This combination of IDIFs and images also provided good slope values
      (1.07+/-0.11). Improved resolution, as obtained with PVC OP-OSEM, changed AUC
      ratios to 1.14+/-0.35 and, for tracer kinetic analysis, slopes changed to 0.95+/
      0.13. For all reconstructions, non-calibrated IDIFs gave poorer results (>61+/
      34% higher slopes) compared with calibrated IDIFs. The results of this study
      indicate that the use of IDIFs, extracted from OP-OSEM or PVC OP-OSEM images, is
      feasible for dynamic HRRT data, thereby obviating the need for online arterial
      sampling.

PMID- 18707008
TI  - Symmetric abnormalities in sulcal patterning in schizophrenia.
AB  - To compare the morphology of the cerebral cortex and its characteristic pattern
      of gyri and sulci in individuals with and without schizophrenia, T1-weighted
      magnetic resonance scans were collected, along with clinical and cognitive
      information, from 33 individuals with schizophrenia and 30 healthy individuals
      group-matched for age, gender, race and parental socioeconomic status. Sulcal
      depth was measured across the entire cerebral cortex by reconstructing surfaces
      of cortical mid-thickness (layer 4) in each hemisphere and registering them to
      the human PALS cortical atlas. Group differences in sulcal depth were tested
      using methods for cluster size analysis and interhemispheric symmetry analysis. A
      significant group difference was found bilaterally in the parietal operculum,
      where the average sulcal depth was shallower in individuals with schizophrenia.
      In addition, group differences in sulcal depth showed significant bilateral
      symmetry across much of the occipital, parietal, and temporal cortices. In
      individuals with schizophrenia, sulcal depth in the left hemisphere was
      correlated with the severity of impaired performance on tests of working memory
      and executive function.

PMID- 18707009
TI  - Methods in safety pharmacology in focus.
AB  - This focused issue of the Journal of Pharmacological and Toxicological Methods is
      the fifth to highlight Methods in Safety Pharmacology and includes a number of
      articles from the 7th Annual Safety Pharmacology Society (SPS) meeting that was
      held in Edinburgh, Scotland, September 19-21, 2007. However, unlike issues of the
      past, in which content predominantly focused on cardiovascular issues
      (specifically QT interval prolongation, QT-HR correction methods and validation
      of non-clinical cardiovascular models) this issue is composed of a number of non
      cardiovascular methods papers and review articles. Of particular interest to
      readers will be articles related to CNS studies, in particular neurobehavioral
      assessments in non-human primates and the effects of drugs in juvenile and adult
      rats (an article that may be relevant in light of recent EU/US pediatric
      legislation). While cardiovascular function may not dominate there are several
      useful methodological papers including an assessment of cardiovascular
      sensitivity of drugs in conscious and anesthetized non-human primates, and a
      mathematical model (fractal analysis) applied to canine heartbeat dynamics. A
      first for the journal is a paper by Vargas et al., (2008-this issue) in which
      members of the SPS formed a working group in order to assess and review safety
      pharmacology testing of biological therapeutic agents (specifically monoclonal
      antibodies, mAbs). The group provides recommendations that will likely shape
      regulatory strategy and discussions in the yet to be fully discussed area of
      biological safety testing. In the tradition of obtaining a perspective on
      industry safety pharmacology program practices Lindgren et al., (2008-this issue)
      provide the results of a recent SPS survey that examines ICH S7A and S7B trends,
      aspects of early 'frontloading' safety studies, abuse and dependence liability
      and Contract Research Organization (CRO) tests/assays used in safety assessment
      of core battery and supplementary organ systems. In keeping with the translation
      track aspect of the 2007 meeting is an overview of the Distinguished Service
      Award lecture to Dr. T. Hammond that discusses many aspects of safety
      pharmacology including its evolution, impact, value and translation of non
      clinical findings to humans. Finally, perspectives are presented on the use of
      the zebrafish as an early safety pharmacology-screening assay.

PMID- 18707010
TI  - Paradoxical sleep deprivation impairs acquisition, consolidation, and retrieval
      of a discriminative avoidance task in rats.
AB  - The aim of the present study was to investigate the effects of paradoxical sleep
      deprivation (PSD) for 96 h on the learning/memory processes in rats submitted to
      the plus-maze discriminative avoidance task (PM-DAT), which simultaneously
      evaluates learning, memory, anxiety and motor function. Four experiments were
      performed in which rats were submitted to: (1) post-training and pre-test PSD;
      (2) post-training or pre-test PSD; (3) pre-training PSD or pre-training
      paradoxical sleep (PS) rebound (24 h) and (4) pre-test PSD rebound. Concerning
      Experiment I, post-training and pre-test PSD induced memory deficits, an
      anxiolytic-like behavior and an increase in locomotor activity. In Experiment II,
      both post-training PS-deprived and pre-test PS-deprived groups showed memory
      deficits per se. However, only the pre-test PS-deprived animals presented
      anxiolytic-like behavior and increased locomotor activity. In Experiment III, pre
      training PS-deprived rats showed learning and memory deficits, anxiolytic-like
      behavior and increased locomotor activity. A 24h-sleep recovery period after the
      PSD abolished the learning and memory deficits but not anxiety and locomotor
      alterations. Finally, sleep rebound did not modify acquisition (Experiment III)
      and retrieval (Experiment IV). This study strengthened the critical role of
      paradoxical sleep (but not sleep rebound) in all the phases of learning and
      memory formation. In addition, it suggests that PSD effects on acquisition and
      consolidation do not seem to be related to other behavioral alterations induced
      by this procedure.

PMID- 18707011
TI  - Chronic stress modulates the use of spatial and stimulus-response learning
      strategies in mice and man.
AB  - Acute stress modulates multiple memory systems in favor of caudate nucleus
      dependent stimulus-response and at the expense of hippocampus-dependent spatial
      learning and memory. We examined in mice and humans whether chronic stress has
      similar consequences. Male C57BL/6J mice that had been repeatedly exposed to rats
      ("rat stress") used in a circular hole board task significantly more often a
      stimulus-response strategy (33%) than control mice (0%). While velocity was
      increased, differences in latency to exit hole, distance moved or number of holes
      visited were not observed. Increased velocity and performance during retention
      trials one day later indicates altered emotionality and motivation to explore in
      rat stressed mice. Forty healthy young men and women were split into "high
      chronic stress" and "low chronic stress" groups based on their answers in a
      chronic stress questionnaire ("Trier Inventory of Chronic Stress"-TICS) and
      trained in a 2D task. A test trial immediately after training revealed that
      participants of the "high chronic stress" group used the S-R strategy
      significantly more often (94%) than participants of the "low chronic stress"
      group (52%). Verbal self-reports confirmed the strategy derived from
      participants' choice in the test trial. Learning performance was unaffected by
      the chronic stress level. We conclude that one consequence of chronic stress is
      the shift to more rigid stimulus-response learning, that is accompanied by
      changes in motivational factors in mice.

PMID- 18707012
TI  - BDNF is a novel marker of cognitive function in ageing women: the DR's EXTRA
      Study.
AB  - Brain-derived neurotrophic factor (BDNF) is one of the key molecules modulating
      brain plasticity. While low circulating levels of BDNF have been suggested to
      predispose to Alzheimer's disease, very little data are available on its
      association with cognitive function in general population. We evaluated the
      association between plasma BDNF levels and cognition in a representative
      population sample of ageing men and women. The subjects (n=1389) were
      participants of the Dose-Responses to Exercise Training (DR's EXTRA) Study and
      represent a random sample of Eastern Finnish people (684 men and 705 women), 57
      79 years of age at baseline of the study. Plasma BDNF levels were measured by
      enzyme-linked immunosorbent assay (ELISA). Cognitive function was evaluated using
      the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
      neuropsychological test battery. Women had a higher mean (+/-SEM) plasma BDNF
      level than men (1721+/-55vs. 1495+/-54pg/ml, P<0.001). In women, 1 SD decrease in
      BDNF increased the risk for a low score in Naming Test by 53% (95% CI 1.21-1.92,
      P<0.001), in Mini-Mental State Examination by 63% (95% CI 1.21-2.20, P=0.001), in
      Word List Memory by 56% (95% CI 1.08-2.26, P=0.019), in Word List Recall by 50%
      (95% CI 1.10-2.05, P=0.010), in Word List Saving by 49% (95% CI 1.12-1.99,
      P=0.007), and in Word List Recognition by 64% (95% CI 1.19-2.25, P=0.002). Data
      were adjusted for age, education, depression, impaired glucose metabolism,
      cardiovascular disease, antihypertensive medication, lipid lowering medication,
      use of sex hormones, smoking, alcohol consumption, storing time of plasma in the
      freezer and platelet count. BDNF was not associated with cognition in men.
      Present data suggest that plasma BDNF is a biomarker of impaired memory and
      general cognitive function in ageing women.

PMID- 18707013
TI  - Chromatin dynamics during the plant cell cycle.
AB  - Cell cycle progression depends on a highly regulated series of events of which
      transcriptional control plays a major role. In addition, during the S-phase not
      only DNA but chromatin as a whole needs to be faithfully duplicated. Therefore,
      both nucleosome dynamics as well as local changes in chromatin organization,
      including introduction and/or removal of covalent DNA and histone modifications,
      at genes with a key role in cell proliferation, are of primary relevance.
      Chromatin duplication during the S-phase and the chromosome segregation during
      mitosis are cell cycle stages critical for maintenance of epigenetic marks or for
      allowing the daughter products to acquire a distinct epigenetic landscape and,
      consequently, a unique cell fate decision. These aspects of chromatin dynamics
      together with the strict coupling of cell proliferation, cell differentiation and
      post-embryonic organogenesis have a profound impact on plant growth, development
      and response to external signals.

PMID- 18707014
TI  - Stimulatory effects of bioamines norepinephrine and dopamine on locomotion of
      Pyrrhocoris apterus (L.): is the adipokinetic hormone involved?
AB  - In the present paper we studied the effects of five biogenic amines -
      norepinephrine, dopamine, octopamine, serotonin and histamine - on the locomotory
      activity and mobilization of lipids in the adult females of the firebug,
      Pyrrhocoris apterus (L.). We tested the hypothesis (1) whether the stimulation of
      walking activity in the bugs injected with the bioamines is associated also with
      their hyperlipaemic effects, like in the case of adipokinetic hormones (AKHs),
      and (2) whether these effects are direct or mediated through a release of the
      AKHs into the hemolymph. The results demonstrated that all five tested biogenic
      amines mobilized the fat body lipids, but only norepinephrine and dopamine were
      capable to enhance the walking activity simultaneously with an elevation of the
      lipid level in the hemolymph. Those two amines had no effect on the level of AKHs
      in CNS, but modulated the AKHs level in hemolymph: norepinephrine increased it,
      while dopamine decreased it. The results indicate an apparent feedback between
      AKH characteristics and dopamine and norepinephrine actions occurring in this
      insect species. While the stimulatory effects of norepinephrine on lipid
      mobilization and walking activity could involve the release of bug's own AKHs,
      dopamine probably employs an independent stimulatory pathway.

PMID- 18707015
TI  - Development of novel animal infection models for the study of acute and chronic
      Burkholderia pseudomallei pulmonary infections.
AB  - Burkholderia pseudomallei causes the disease melioidosis. The most common
      clinical presentation of melioidosis is pneumonia which can occur in acute and
      chronic forms. The tsunami of 2004 demonstrated a new risk factor for the
      acquisition of melioidosis and resulted in the proposal that direct delivery of
      B. pseudomallei into the lungs may result in the enhanced ability of this
      pathogen to cause disease. In the present studies, we present the development and
      characterization of rat models of acute and chronic pulmonary melioidosis, and we
      have utilized these models to demonstrate that direct delivery of B. pseudomallei
      into the lungs does indeed result in the enhanced ability of this pathogen to
      cause disease. Importantly, the rat lung infection models for melioidosis can
      quantify differences in virulence between individual B. pseudomallei wild type
      strains during both acute and chronic infections. Further, the histopathology
      associated with pulmonary melioidosis in the rat resembles that seen in
      tuberculosis. B. pseudomallei microarrays were used to characterize gene
      expression patterns during chronic pulmonary infections. Transcriptional
      profiling at several time points during chronic infection revealed that a wide
      range of genes associated with virulence and metabolic functions are
      differentially regulated in vivo during chronic infections.

PMID- 18707016
TI  - Energetic signalling in the control of mitochondrial F1F0 ATP synthase activity
      in health and disease.
AB  - The mitochondrial F1F0 ATP synthase is a critical enzyme that works by coupling
      the proton motive force generated by the electron transport chain via proton
      transfer through the F0 or proton-pore forming domain of this enzyme to release
      ATP from the catalytic F1 domain. This enzyme is regulated by calcium, ADP, and
      inorganic phosphate as well as increased transcription through several pathways.
      This enzyme is also an ATP hydrolase under ischemic conditions. This
      "inefficient" hydrolysis of ATP consumes 90% of ATP consumed during ischemia as
      shown with non-selective ATPase inhibitors oligomycin and Aurovertin B. A
      benzopyran analog, BMS-199264, selectively inhibits F1F0 ATP hydrolase activity
      with no effect on ATP synthase activity. BMS-199264 had no effect on ATP before
      ischemia, but reduced the decline in ATP during ischemia. Selective hydrolase
      inhibition seen with the small molecule BMS-199264 suggests a conformational
      change in the F1F0 ATPase enzyme when switching from synthase to hydrolase
      activity.

PMID- 18707017
TI  - Gene expression profile of adult human bone marrow-derived mesenchymal stem cells
      stimulated by the chemokine CXCL7.
AB  - A variety of chemokines has been shown to recruit human bone marrow-derived
      mesenchymal stem cells (MSC) and may be potential candidates for chemokine-based
      tissue regeneration approaches. The aim of our study was to determine whether the
      chemokine CXCL7 stimulates migration of human bone marrow-derived MSC and to
      analyze the effect of CXCL7 on the recruitment of MSC on the broad molecular
      level. Chemotaxis assays documented that high doses of CXCL7 significantly
      recruited MSC. Gene expression profiling using oligonucleotide microarrays showed
      that MSC treated with CXCL7 differentially expressed genes related to cell
      migration, cell adhesion and extracellular matrix remodeling. Pathway analysis
      showed that CXCL7 induced the expression of all chemokines binding the
      interleukin (IL) receptors A and B, CXCR1 and CXCR2, as well as the IL6 signal
      transducer (gp130) and its ligands IL6 and leukemia inhibitory factor (LIF).
      Induction of differentially expressed chemokines CXCL1-3, CXCL5, and CXCL6 as
      well as LIF and gp130 in MSC by CXCL7 was verified by real-time polymerase chain
      reaction. Immunoassay of cell culture supernatants confirmed elevated levels of
      the interleukins 6 and 8 in MSC upon treatment with CXCL7. Chemotaxis assays
      showed that interleukin 6 did not recruit MSC. In conclusion, CXCL7 significantly
      stimulates the migration of human MSC in vitro. Pathway analysis suggests that
      recruitment of human MSC by CXCL7 is supported by the induction of ligands of the
      interleukin 8 receptors, synergistically activating the respective signaling
      pathways.

PMID- 18707019
TI  - Several novel approaches to developing therapeutics that target both bacterial
      and human proteins.

PMID- 18707018
TI  - High mobility group box-1 protein acts as a coactivator of nuclear factor of
      activated T cells-2 in promoting interleukin-2 transcription.
AB  - High mobility group box-1 protein, an abundant and conserved constituent of
      vertebrate nuclei, has recently been reported to be an endogenous immune signal
      [Rovere-Querini P, Capobianco A, Scaffidi P, Valentinis B, Catalanotti F, Giazzon
      M, et al. HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO
      Reports 2004;5:825-30]. High mobility group box-1 protein can trigger the release
      of interleukin-2 and interleukin-12 from lymphocytes. However, at present the
      underlying mechanism remains unknown. It has been clarified that nuclear factor
      of activated T cells-2 transduces most immunological signals in T cells and
      modulates the production of interleukin-2. So it is natural that we asked whether
      high mobility group box-1 protein could promote production of interleukin-2 in a
      nuclear factor of activated T cells-2-dependent way. Our experiments firstly
      showed that high mobility group box-1 protein could bind to nuclear factor of
      activated T cells-2 in vivo and in vitro. High mobility group box-1 protein
      cotransfection markedly upregulated the transcription activity of nuclear factor
      of activated T cells-2 in promoting interleukin-2 reporter gene transcription,
      which was demonstrated to be dose-dependent. Cotransfection of high mobility
      group box-1 protein and nuclear factor of activated T cells-2 induced an 18.4
      time increase of interleukin-2 activity in 293T cells and a 117.7-time increase
      in Hela cells. Moreover, inhibition of either high mobility group box-1 protein
      or nuclear factor of activated T cells -2 expression by sRNAi led to significant
      decrease of transcription activity of interleukin-2 reporter gene, suggesting
      that high mobility group box-1 protein and nuclear factor of activated T cells-2
      both take important roles in facilitating interleukin-2 transcription, and high
      mobility group box-1 protein could act as a coactivator for nuclear factor of
      activated T cells-2 in enhancing transcription of interleukin-2. This discovery
      has not been reported elsewhere, and helps to understand the newly highlighted
      immunological role of high mobility group box-1 protein.

PMID- 18707020
TI  - Repair and tolerance of oxidative DNA damage in plants.
AB  - DNA damage caused by exposure to reactive oxygen species is one of the primary
      causes of DNA decay in most organisms. In plants, endogenous reactive oxygen
      species (ROS) are generated not only by respiration and photosynthesis, but also
      by active responses to certain environmental challenges, such as pathogen attack.
      Significant extracellular sources of activated oxygen include air pollutants such
      as ozone and oxidative effects of UV light and low-level ionizing radiation.
      Plants are well equipped to cope with oxidative damage to cellular
      macromolecules, including DNA. Oxidative attack on DNA generates both altered
      bases and damaged sugar residues that undergo fragmentation and lead to strand
      breaks. Recent advances in the study of DNA repair in higher plants show that
      they use mechanisms similar to those present in other eukaryotes to remove and/or
      tolerate oxidized bases and other oxidative DNA lesions. Therefore, plants
      represent a valuable model system for the study of DNA oxidative repair processes
      in eukaryotic cells.

PMID- 18707021
TI  - Lateralizing value of epileptic nystagmus.
AB  - Epileptic nystagmus is a relatively rare clinical seizure presentation. The
      direction is usually determined by the fast component of the eye movement. We
      retrospectively reviewed 1838 consecutive patients admitted to the Epilepsy
      Monitoring Unit at Cleveland Clinic and identified 9 patients (0.5%) with
      epileptic nystagmus. Only two of them were adults. The direction of the nystagmus
      was contralateral to the epileptogenic zone in all patients. In contrast, eye
      version was seen ipsiversive to the epileptic nystagmus in four of the six
      patients in whom both signs were observed. Epileptic nystagmus is a helpful
      lateralizing sign, particularly in pediatric patients.

PMID- 18707022
TI  - The effects of levetiracetam on cognition: a non-interventional surveillance
      study.
AB  - Objective and subjective cognitive measures were evaluated in 401 patients before
      and 3 and 6 months after introducing levetiracetam (LEV). Initially, cognitive
      impairment was indicated in 37-44% of the patients, and subjective impairments in
      32-67%. With LEV, 87% of untreated patients changed to monotherapy, and 94%
      changed from mono- to polytherapy. The rate of retention of LEV was 97%; adverse
      events were reported by 7%. Under LEV, 36% achieved early seizure control, 25%
      achieved late seizure control, 33% continued to have seizures, and 7% had a
      relapse. Very good tolerance was reported by 68%, and cognitive improvement by
      58%. Objective improvement was significant in 23-29% of the patients; 5-6%
      deteriorated. Better baseline scores, later-onset epilepsies, fewer initial
      antiepileptic drugs, and seizure control were predictive of a better cognitive
      outcome. Considering the uncontrolled study design and the increase in total drug
      load, LEV appeared safe and efficacious, and a general subjective and objective
      cognitive improvement could be noted. However, a controlled study design would be
      required to attribute these improvements to a specific drug action.

PMID- 18707023
TI  - Induction of several cytochrome P450 genes by doxorubicin in H9c2 cells.
AB  - Doxorubicin is a potent anti-neoplastic antibiotic used to treat a wide variety
      of malignancies; however, its use is limited by dose dependent cardiotoxicity.
      There is indirect evidence suggesting that doxorubicin cardiotoxicity is CYP
      mediated. In the current study, we investigated the effect of doxorubicin on
      hypertrophic markers, and different CYP gene expression in cardiac derived H9c2
      cells. H9c2 cells were incubated with increasing concentrations of doxorubicin
      and the expressions of different genes were determined by real-time PCR. Our
      results demonstrate that multiple CYP genes are expressed in H9c2 cells and the
      level of expression from the highest to the lowest were; CYP1B1, CYP2B1, CYP2J3,
      CYP1A1, CYP2C11, CYP2C23, CYP2E1, CYP1A2, and CYP2B2. Doxorubicin treatment
      caused an induction of the hypertrophic markers, ANP and BNP. In addition,
      doxorubicin caused a significant induction of CYP1A1, CYP1A2, CYP1B1, CYP2B2,
      CYP2E1, and CYP2J3 gene expression in a concentration-dependent manner. However,
      only the highest concentration tested, 10 muM, caused an induction of CYP2C11;
      whereas, CYP2B1 and CYP2C23 were not altered. Our findings demonstrate that
      doxorubicin induces the hypertrophic markers, ANP and BNP as well as several CYP
      genes in H9c2 cells. Doxorubicin-mediated CYP induction may represent a novel
      mechanism by which this drug induces cardiotoxicity.

PMID- 18707024
TI  - Preliminary phylogenetic identification of virulent Chlamydophila pecorum
      strains.
AB  - Chlamydophila pecorum is an obligate intracellular bacterium associated with
      different pathological conditions in ruminants, swine and koala, which is also
      found in the intestine of asymptomatic animals. A multi-virulence locus sequence
      typing (MVLST) system was developed using 19 C. pecorum strains (8 pathogenic and
      11 non-pathogenic intestinal strains) isolated from ruminants of different
      geographical origins. To evaluate the ability of MVLST to distinguish the
      pathogenic from the non-pathogenic strains of C. pecorum, the sequences of 12
      genes were analysed: 6 potential virulence genes (ompA, incA, incB, incC, mip and
      copN), 5 housekeeping genes (recA, hemD, aroC, efp, gap), and the ORF663 gene
      encoding a hypothetical protein (HP) that includes a variant 15-nucleotides
      coding tandem repeat (CTR). MVLST provided high discriminatory power (100%) in
      allowing to distinguish 6 of 8 pathogenic strains in a single group, and overall
      more discriminatory than MLST targeting housekeeping genes. ompA was the most
      polymorphic gene and the phylogenetic tree based only on its sequence
      differentiated 4 groups with high bootstrap values. The number of CTRs (rich in
      serine, proline and lysine) in ORF663 detected in the pathogenic strains was
      generally lower than that found in the intestinal strains. MVLST appears to be a
      promising method for the differential identification of virulent C. pecorum
      strains, and the ompA, incA and ORF663 genes appear to be good molecular markers
      for further epidemiological investigation of C. pecorum.

PMID- 18707025
TI  - Baculovirus up-regulates antiviral systems and induces protection against
      infectious bronchitis virus challenge in neonatal chicken.
AB  - In this study, the Antheraea pernyi nuclear polyhedrosis virus (ApNPV), a member
      of the baculovirus family, is evaluated for its stimulation of chicken peripheral
      blood mononuclear cells (PBMC) and macrophage cell line HD 11 in vitro, and
      protection against infectious bronchitis virus (IBV) in neonatal chickens in
      vivo. This study showed that ApNPV significantly enhanced inflammatory cytokine
      mRNA expression in chicken PBMC and HD 11 cells through the clathrin-dependent
      endocytic and endosomal maturation pathway, and up-regulated nitric oxide
      production in HD 11 cells. Furthermore, it was identified that budded virus (BV)
      can induce antiviral effects in HD 11 cells contrary to occlusion-derived virus
      (ODV). These results indicate that immunostimulatory BV of ApNPV can stimulate
      the innate immune activities and enhance the resistance to infectious virus of
      neonatal chickens.

PMID- 18707026
TI  - Effects of the bacterial transcription-repair coupling factor during
      transcription of DNA containing non-bulky lesions.
AB  - Transcription-coupled DNA repair is a mechanism by which bulky DNA lesions that
      block transcription by RNA polymerase are prioritised for removal by the
      nucleotide excision repair apparatus. The trigger is thought to be the presence
      of an irreversibly blocked transcription complex, which is recognised by a
      transcription-repair coupling factor. Many common DNA lesions do not block
      transcription, but are bypassed with varying degrees of efficiency and with
      potentially mutagenic effects on the RNA transcripts that are produced. The
      effect of the bacterial transcription-repair coupling factor, Mfd, at such
      lesions is not known: it has been suggested that Mfd may promote mutagenesis by
      increasing the efficiency with which RNA polymerase bypasses non-bulky lesions,
      but it has also been reported that 8-oxoguanine, a major product of oxidative DNA
      damage that is efficiently bypassed by RNA polymerase, is subject to Mfd
      dependent transcription-coupled repair in Escherichia coli. We have investigated
      the effect of Mfd during transcription of templates containing 8-oxoguanine, and
      various other non-bulky lesions. We show that an 8-oxoguanine in the template
      strand induces a transient pause in transcription, and that Mfd neither increases
      nor decreases the efficiency with which RNA polymerase bypasses the lesion. We
      also show that Mfd can displace a transcription complex stalled at a single
      strand nick, and that it decreases the efficiency with which RNA polymerase
      bypasses an abasic site. These activities are not affected by transcription rate,
      as similar results were obtained using "fast" and "slow" mutant RNA polymerases.
      Our findings suggest that 8-oxoguanine is unlikely to be directly targeted by the
      transcription-coupled repair pathway, and identify a potential role for Mfd in
      reducing the level of transcriptional mutagenesis caused by abasic sites.

PMID- 18707027
TI  - Hepatitis C virus-related arthritis.
AB  - Although asymptomatic joint involvement and arthralgias are frequent in patients
      with hepatitis C virus chronic infection (HCV), a true arthritis affects only up
      to 4% of the subjects. HCV-related arthritis (HCVrA) is usually distinguished in
      two clinical subsets: a more frequent symmetrical polyarthritis (SP), similar to
      rheumatoid arthritis but much less serious, and an intermittent mono
      oligoarthritis (IMO) that involves medium and large sized joints, mainly the
      ankle. This latter subset is strictly related to the presence of HCV-induced
      mixed cryoglobulinemia and its cutaneous manifestations, in particular purpura.
      According to recent reports, anti-CCP antibodies are considered very useful in
      differentiating the SP subset from rheumatoid arthritis. The treatment of HCVrA
      is still largely empirical because few studies have analyzed this topic. However,
      COXIBs, NSAIDs, low doses of corticosteroids, hydroxychloroquine and less
      frequently methotrexate and penicillamine have been used with partial or complete
      control of symptoms. On the basis of recent studies, the administration of
      cyclosporine also seems to be sufficiently safe. The scarcely aggressive nature
      of HCVrA does not favour the use of anti-TNF agents. Specific anti-viral therapy
      (interferon-alpha+ribavirin) must be accurately evaluated because interferon
      alpha can induce the development or the worsening of several autoimmune HCV
      related disorders including arthritis.

PMID- 18707028
TI  - Pemphigus and infectious agents.
AB  - Pemphigus is a group of autoimmune bullous diseases characterized by a loss of
      cell adhesion and blister formation within the epidermis in the skin and/or the
      mucosal surfaces. Pemphigus develops due to the interaction between predisposing
      genetic factors and environmental factors. Among the latter, infectious agents
      such as viruses and bacteria were reported as preceding or exacerbating pemphigus
      disease. In this article we review the literature concerning the relationship
      between pemphigus, viral and bacterial pathogens.

PMID- 18707029
TI  - Infections, rheumatism and autoimmunity: the conflicting relationship between
      humans and their environment.

PMID- 18707030
TI  - Panic disorder and control of breathing.
AB  - Anxiety disorders, particularly panic disorder (PD), are associated with
      respiratory abnormalities. PD consists of unexpected panic attacks (PA) with
      anxiety, fear and many autonomic and respiratory symptoms. There is a substantial
      body of literature demonstrating that stimulation of respiration is a common
      event in panic disorder patients during PA. A number of abnormalities in
      respiration, such as enhanced CO(2) sensitivity, have been detected in PD
      patients. As a result, some investigators advanced that there is a fundamental
      abnormality in the physiological mechanisms that control breathing in PD. Studies
      indicate that PD patients with dominant respiratory symptoms are particularly
      sensitive to respiratory tests compared with those who do not manifest dominant
      respiratory symptoms, possibly representing a distinct subtype. Accumulated
      evidence suggests that respiratory physiology remains normal in PD patients and
      that their tendency to hyperventilate and to react with panic to respiratory
      stimulants like CO(2) represents the triggering of a hypersensitive fear network.
      However, some recent evidences support the presence of subclinical abnormalities
      in respiration and other functions related to body homeostasis. The fear network,
      composed by the hippocampus, the medial prefrontal cortex, the amygdala and its
      brainstem projections, may be abnormally sensitive in PD patients. This theory
      might explain why both medication and psychosocial therapies are clearly
      effective. The evidence of abnormalities in several neurochemical systems might
      be just the expression of the complex interactions among brain circuits. Our aim
      was to review the relationship between respiration and panic disorder, addressing
      the respiratory subtype of panic disorder, the hyperventilation syndrome, the
      respiratory challenge tests, the current mechanistic concepts and the
      pharmacological implications.

PMID- 18707031
TI  - Neurochemical phenotypes of cardiorespiratory neurons.
AB  - Interactions between the cardiovascular and respiratory systems have been known
      for many years but the functional significance of the interactions is still
      widely debated. Here I discuss the possible role of metabotropic receptors in
      regulating cardiorespiratory neurons in the brainstem and spinal cord. It is
      clear that, although much has been discovered, cardiorespiratory regulation is
      certainly one area that still has a long way to go before its secrets are fully
      divulged and their function in controlling circulatory and respiratory function
      is revealed.

PMID- 18707032
TI  - Evaluation of two cell surface modification methods for proteomic analysis of
      plasma membrane from isolated mouse hepatocytes.
AB  - The hepatocyte is a highly polarized cell with a heterogeneous distribution of
      plasma-membrane (PM) proteins. To reduce the complexity of the proteome of liver
      tissue and give a comprehensive profile of hepatocyte PM, two PM purification
      methods based on cell surface modification, named the biotin-avidin (BA) and
      cationic silica-polyanion (CSP) strategies were evaluated and compared with the
      traditional cell fractionation method to prepare highly enriched PM from freshly
      isolated C57 mouse hepatocytes. Employing different principles for PM
      modification, both methods were effective in the isolation of general and
      purified PM fraction. The CSP strategy showed better yield for the PM
      purification from freshly isolated hepatocytes. 189 non-redundant proteins were
      identified, including 49 from the BA method and 185 from CSP strategy. Many known
      and novel PM-associated proteins were also found. Our evaluation here should give
      implications for PM preparation from other freshly isolated tissue-derived cells.
      The hepatocyte PM proteins identified here should be taken as a references for
      the PM-related functional and diseases research.

PMID- 18707033
TI  - Clinical variability of the 22q11.2 duplication syndrome.
AB  - The 22q11.2 duplication syndrome is an extremely variable disorder with a
      phenotype ranging from normal to learning disability and congenital defects. Both
      patients with a de novo 22q11.2 duplication and patients in whom the duplication
      has been inherited from a phenotypically normal parent have been reported. In
      this study we present two familial cases with a 3Mb 22q11.2 duplication detected
      by array-CGH. We also review the findings in 36 reported cases with the aim of
      delineating the phenotype of the 22q11.2 duplication syndrome. In a majority of
      the reported cases where parents have been tested, the duplication seems to have
      been inherited from a normal parent with minor abnormalities. With this in mind
      we recommend that family members of patients with a 22q11.2 duplication to be
      tested for this genetic defect.

PMID- 18707035
TI  - Neural stem cell delivery to the spinal cord in an ovine model of fetal surgery
      for spina bifida.
AB  - BACKGROUND: We introduce the notion of prenatal neural stem cell (NSC) delivery
      to the spinal cord as an adjuvant to fetal repair of spina bifida. METHODS: Fetal
      lambs with experimental myelomeningocele (MMC; n = 25) were divided in 3 groups:
      group I, no repair; group II, standard surgical MMC coverage; and group III, MMC
      coverage plus delivery of a murine NSCs clone into the spinal cord defect. Donor
      cells constitutively expressed lacZ encoding for Escherichia coli beta
      galactosidase, yet they were further labeled by exposure to either BrdU and/or to
      the fluorescent membrane dye PKH-26. Blinded initial clinical evaluations and
      multiple spinal cord analyses were undertaken soon after birth. RESULTS: Both
      survival and the incidence of major paraparesis were significantly worse in group
      I compared with groups II and III. In group III, NSC density was highest within
      the most damaged areas of the spinal cord, with selective engraftment within
      those regions. Donor NSCs retained an undifferentiated state in vivo, producing
      neurotrophic factors within the defect. No animals in group III had a worsened
      condition following this intervention. CONCLUSIONS: Neural stem cells retain an
      undifferentiated state and produce neurotrophic factors in the short term after
      delivery to the fetal spinal cord, in the setting of experimental MMC. Further
      scrutiny of NSC delivery to the spinal cord as a therapeutic strategy against
      spina bifida is warranted.

PMID- 18707036
TI  - Hepatocyte growth factor improves survival after partial hepatectomy in cirrhotic
      rats suppressing apoptosis of hepatocytes.
AB  - BACKGROUND: Liver failure after hepatic resection is still a critical issue in
      the treatment of hepatic tumors in patients with liver cirrhosis. In the current
      study, the effect of hepatocyte growth factor (HGF) gene transfer, which is a
      multipotent growth factor, was examined in rats with liver cirrhosis that
      underwent 2/3 partial hepatectomy (PH). METHODS: Rats were treated with 1 mL of
      1% dimethylnitrosoamine (DMN) 3 consecutive days per week for 4 weeks and then
      received a 2/3 PH. Three days before the PH, human HGF gene plasmid (20 microg)
      encapsulated in hemagglutinating virus of Japan (HVJ)-liposome was administered
      through a direct injection in the portal vein. Control cirrhotic rats received
      empty HVJ-liposome in the same manner. RESULTS: HGF gene transfer significantly
      improved survival after PH in the cirrhotic rats, and it stimulated BrdU uptake
      in hepatocytes. Although the HGF gene transfer did not change the liver
      regeneration rate after PH, it suppressed hepatocyte apoptosis and upregulated an
      antiapoptotic protein, Bcl-xl, but it did not affect the expression of Bax, which
      is a proapoptotic protein. CONCLUSION: HGF gene transfer to cirrhotic livers
      improves liver failure-associated death after PH upregulating expression of an
      antiapoptotic protein, Bcl-xl.

PMID- 18707037
TI  - Cholestatic liver damage is mediated by lymphocyte function antigen-1-dependent
      recruitment of leukocytes.
AB  - BACKGROUND: The role of specific adhesion molecules in cholestasis-induced
      leukocyte recruitment in the liver is not known. Therefore, the aim of our
      experimental study was to evaluate the role of lymphocyte function antigen-1 (LFA
      1) in cholestatic liver injury. METHODS: C57BL/6 mice underwent bile duct
      ligation for 12 hours. Mice were pretreated with an anti-LFA-1 antibody or
      control antibody. Subsequently, hepatic accumulation of leukocytes and sinusoidal
      perfusion were determined by means of intravital fluorescence microscopy.
      Hepatocellular damage was monitored by measuring serum levels of alanine
      aminotransferase and aspartate aminotransferase. CXC chemokines in the liver were
      determined by enzyme-linked immunosorbent assay. RESULTS: Bile duct ligation
      provoked clear-cut recruitment of leukocytes and liver damage, as indicated by
      increased serum activities of liver enzymes and sinusoidal perfusion failure.
      Neutrophils expressed greater levels of LFA-1 and inhibition of LFA-1
      significantly decreased serum activity of alanine aminotransferase and aspartate
      aminotransferase levels in cholestatic mice. Immunoneutralization of LFA-1
      reduced leukocyte adhesion in postsinusoidal venules that had been induced by
      bile duct ligation, whereas leukocyte rolling and sinusoidal accumulation were
      not changed. Moreover, blocking LFA-1 function restored sinusoidal perfusion in
      cholestatic animals. CONCLUSION: These findings demonstrate an important role of
      LFA-1 in supporting cholestasis-induced leukocyte recruitment in the liver. Thus,
      targeting LFA-1 may help to protect against pathologic inflammation and liver
      damage in cholestatic liver diseases.

PMID- 18707034
TI  - Regulation of metastasis in colorectal adenocarcinoma: a collision between
      development and tumor biology.

PMID- 18707038
TI  - A novel animal model of severe pancreatitis in mice and its differences to the
      rat.
AB  - BACKGROUND: A noninvasive model of necrohemorrhagic pancreatitis induced by
      simultaneous intravenous cerulein/enterokinase (EK) infusion has recently been
      established in rats. The aim of the present study was to establish this new model
      in mice and to compare it with the rat model. METHODS: Male Balb/C mice (20 to 25
      g) were used for the experiments. Pancreatitis was induced by simultaneous
      intravenous infusion of cerulein and EK. Controls were infused with either 0.9%
      NaCl, cerulein, or EK. Animals were humanely killed 6 hours after start of
      infusions. Pancreatic and pulmonary injury was assessed by histology, wet-to-dry
      weight ratio, and myeloperoxidase activity. Systemic cytokine, amylase, and
      lactate dehydrogenase (LDH) levels in blood were measured to assess pancreatic
      and systemic inflammatory response. To evaluate the role of protease activity in
      this model, trypsin, cathepsin B, and elastase activity were measured in
      pancreatic tissue. Survival experiments were performed to determine survival time
      and tissue injury in the later course of the disease. RESULTS: Mice with
      simultaneous cerulein/EK infusion developed marked local and systemic organ
      injury compared with those animals who received cerulein or EK alone. Pancreatic
      and pulmonary injury increased with high concentrations of cerulein/EK infusions.
      Survival decreased in these animals. Whereas acinar cell apoptosis was an early
      finding, pancreatic necrosis was observed later in the course of the disease.
      Serum levels of LDH, interleukin (IL)-1 alpha, and IL-1 beta reflected cell
      damage and the systemic inflammatory response. Protease activity in pancreatic
      tissue was greatest in animals with simultaneous cerulein/EK infusion.
      CONCLUSIONS: Using intravenous cerulein/EK infusions, a model of lethal acute
      pancreatitis has been established in mice. Major pancreatic edema, acinar cell
      apoptosis and necrosis, and pulmonary leukocyte sequestration are characteristic
      findings in this model. Although pancreatic injury was not as strong as in the
      rat model, this model may prove useful for future studies in transgenic mice.

PMID- 18707039
TI  - The preventive effect of Met-RANTES on postoperative intraperitoneal adhesion
      formation in the rat model.
AB  - BACKGROUND: Chemokines are proinflammatory proteins that participate in immune
      and inflammatory responses through chemoattraction and leukocyte activation. The
      chemokine antagonist Met-RANTES (Regulated upon Activation Normal T cell
      Expressed and Secreted) has been shown to be efficacious in decreasing
      inflammation in several animal disease models. The purpose of this study was to
      investigate the effects of administration of Met-RANTES on intra-abdominal
      adhesion formation after abdominal operation. MATERIALS AND METHODS: A 42 and 4
      month-old female Wistar-Albino rats were subjected to standardized lesions by
      cauterization of the cecum and uterine horn. They were divided randomly into 3
      groups containing 14 rats each: group 1 (control), operative procedure without
      further treatment; group 2 (Seprafilm), operative procedure with an antiadhesive
      membrane; 2 x 1 cm of Seprafilm was interposed beneath the peritoneal incision,
      and group 3 (Met-RANTES), operative procedure with the chemokine antagonist Met
      RANTES. The extent and severity of adhesions at the operative site were
      evaluated. Light microscopic examination was performed to determine
      semiquantitative scores of VEGF expression. RESULTS: Rats in the control group
      formed extensive adhesions. In comparison with the control group, the adhesion
      scores were significantly lower in the 2 other groups. The immunohistochemical
      grading scores of vascular endothelial growth factor correlated closely with the
      total adhesion scores and were less in groups 2 and 3 (P < .005). CONCLUSIONS:
      Selective chemokine suppression with Met-RANTES seems to decrease rates, extent,
      and severity of postoperative intraperitoneal adhesions.

PMID- 18707040
TI  - Jejunal cholinergic, nitrergic, and soluble guanylate cyclase activity in
      postoperative ileus.
AB  - BACKGROUND: In animal models of postoperative ileus (POI), inflammation of the
      intestine plays an important role in the pathogenesis of POI. Changes in alpha(2)
      adrenoceptors and nitrergic regulation have been proposed to be implicated. The
      aim of our study was to investigate the presynaptic alpha(2)-receptor-mediated
      control of cholinergic nerve activity, the nitrergic nerve activity, and the
      possible role of soluble guanylate cyclase (sGC) during the inflammatory phase of
      POI. METHODS: Ileus was induced by anesthesia and manipulation of the rat
      jejunum. Rats were treated with the sGC inhibitors methylene blue or ODQ;
      nonoperated animals served as controls. After 24 h, plasma and jejunal tissue
      were collected for biochemical assays, nitric oxide synthase-1 (NOS-1)
      immunohistochemistry, acetylcholine (Ach)-release experiments, and muscle tension
      experiments. RESULTS: In all operated animal groups, myeloperoxidase activity was
      significantly increased, which indicates initiation of an inflammatory response.
      The alpha(2)-adrenoceptor agonist UK14,304 reduced electrically induced Ach
      release similarly in operated and nonoperated animals. In strips of operated
      animals, electrically induced nitrergic relaxations were decreased, whereas
      relaxations induced by exogenous nitric oxide (NO) remained unchanged compared
      with control. The number of myenteric neurons and the percentage of NOS-1
      positive neurons were not influenced. Plasmatic cyclic guanosine monophosphate
      (cGMP) levels were decreased in all operated groups, whereas jejunal cGMP levels
      were unchanged compared with nonoperated controls; treatment with sGC inhibitors
      did not reduce plasmatic cGMP levels. CONCLUSIONS: This study demonstrates that
      presynaptic alpha(2)-receptor mediated control of intestinal cholinergic nerve
      activity is unchanged during manipulation-induced inflammation. However, this
      inflammation induces impaired nitrergic neurotransmission related to decreased
      NOS-1 activity in the nitrergic nerves.

PMID- 18707041
TI  - Early tissue incorporation and collagen deposition in lightweight polypropylene
      meshes: bioassay in an experimental model of ventral hernia.
AB  - BACKGROUND: This study was designed to assess the early host tissue incorporation
      of several polypropylene lightweight (PP-LW) meshes used to repair abdominal wall
      defects and to correlate collagen deposition with the biomechanical response
      shown by PP-LW versus polypropylene heavyweight (PP-HW) meshes. METHODS: Ventral
      hernial defects (7 x 5 cm) were created in the anterior abdominal wall of New
      Zealand rabbits and repaired by fixing PP-LW mesh of different pore sizes or a
      low porosity HW mesh to the edges of the defect. Rabbits were killed 14 days
      after implant, and specimens were taken from the central mesh area to examine
      collagen deposition by light microscopy, real time reverse transcription
      polymerase chain reaction, immunohistochemistry, and Western blotting. The
      biomechanical resistance of the biomaterials was also assessed. RESULTS: All the
      materials showed excellent incorporation in host tissue. Relative amounts of
      collagen III mRNA were considerably higher than collagen I mRNA. Higher collagen
      I and III mRNA levels were noted for pore sizes equal to or greater than 3.45 +/-
      0.19 mm(2) (Ultrapro/Optilene Elastic. These two meshes showed significantly
      higher levels of collagen III than Parietene and Surgipro with smaller pores.
      Biomechanical resistance values for Optilene were significantly higher than those
      recorded for Surgipro and Parietene. CONCLUSIONS: (a) LW meshes of pore size
      larger than 3 mm(2) induced the genetic overexpression of collagen types I and
      III; (b) the larger pore-sized LW meshes induced more collagen type III
      deposition and its faster conversion to collagen I; (c) Optilene, the most porous
      LW mesh examined, showed the greatest tensile strength 14 days after implant.

PMID- 18707043
TI  - Laparoendoscopic "rendezvous" versus laparoscopic antegrade sphincterotomy for
      choledocholithiasis.
AB  - BACKGROUND: The ideal management of common bile duct stones in the era of
      laparoscopic cholecystectomy is controversial. With rapid advances in technology
      and more experience in laparoscopic skills, many surgeons are now routinely
      performing single-stage procedures and questioning the wisdom of preoperative
      endoscopic retrograde cholangiopancreotography, with or without sphincterotomy.
      The purpose of this study was to compare the success rate, duration of operating
      time, clinical results, and duration of hospital stay of a laparoendoscopic
      "rendezvous" technique versus antegrade sphincterotomy in patients with
      cholecystitis-choledocholithiasis. METHODS: Patients with gallbladder and common
      bile duct stones undergoing laparoscopic cholecystectomy plus retrograde
      sphincterotomy (group A; n = 35) were compared retrospectively with those
      undergoing laparoscopic cholecystectomy plus antegrade sphincterotomy (group B; n
      = 41) at a single institution. RESULTS: Ductal stone clearance was equivalent in
      the 2 groups (94% vs 95%; P = .979), as was morbidity (9% vs 5%; P = .545) and
      conversion (6% vs 5%; P = .877). The median operating time was less in group B
      (89 vs 117 minutes; P < .0001). There was no significant difference in hospital
      stay between the 2 groups (P = .140). CONCLUSION: This study suggests that
      intraoperative sphincterotomy with a combined endoscopic-laparoscopic approach
      for the removal of common bile duct stone(s) is safe and effective in routine
      surgical practice. Ductal stone(s) clearance, morbidity, and conversion were
      equivalent in the 2 groups; antegrade sphincterotomy had a shorter operative time
      compared with the rendezvous technique.

PMID- 18707042
TI  - Benefit of laparoscopy for rectal resection in patients operated simultaneously
      for synchronous liver metastases: preliminary experience.
AB  - BACKGROUND: Resection of the rectal primary neoplasm with synchronous liver
      metastases (LM) is warranted, because this is the only strategy with curative
      potential. Combined resection remains controversial because of the risk of
      morbidity and necessity of a curative abdominal approach to warrant liver
      resection. Laparoscopic colorectal resection may be beneficial and could
      facilitate this procedure. METHODS: Between February 2006 and June 2007, 10
      patients underwent 1-step laparoscopic resection for primary rectal cancer
      combined with open resection of synchronous LM. RESULTS: All patients underwent a
      laparoscopic mesorectal excision (n = 10). Liver resections included right
      hepatectomy (n = 1), bi- or trisegmentectomy (n = 3), and metastasectomy (n = 6).
      The rectosigmoid specimen was extracted through the right subcostal or a short
      midline incision used for open liver resection, except in 3 patients who
      underwent a 1-step totally laparoscopic resection of both the colorectal and
      hepatic neoplasms. The overall morbidity was 40%. The median hospital stay was 12
      days (range, 5-40). Overall morbidity (29% vs 40%) and hospital stay (12 vs 12
      days) were similar to those observed in a previous cohort of 27 patients
      undergoing laparoscopic mesorectal excision only. CONCLUSION: This pilot study
      suggests that laparoscopic rectal resection with synchronous resection of LM is
      feasible with low morbidity and short hospital stay. Moreover, laparoscopy
      facilitates the operation approach for synchronous major hepatectomy.

PMID- 18707044
TI  - Hypophosphatemia after live donor right hepatectomy.
AB  - BACKGROUND: It is known that hypophosphatemia can frequently develop after
      hepatectomy and may result from an increased renal phosphate leak. However, its
      clinical significance has not been well defined in live donor right hepatectomy
      (LDRH). The purpose of this study was to investigate the correlation between
      postoperative hypophosphatemia and both donor morbidity and the degree of hepatic
      resection in LDRH. METHODS: In all, 88 live liver donors were enrolled, who had
      undergone right hemihepatectomy between January 2002 and December 2005. Based on
      the severity of the postoperative hypophosphatemia, we divided the donors into 3
      groups: mild (1.5-2.5 mg/dL, n = 30), moderate (1.0-1.5 mg/dL, n = 41), and
      severe (<1.0 mg/dL, n = 17), and we compared the incidence of complications among
      these groups. In addition, we investigated the possible correlation between the
      nadir phosphorus levels and both remnant liver volume and alkaline phosphate
      (ALP) levels. RESULTS: All donors developed hypophosphatemia postoperatively. The
      mean value of the nadir phosphorus levels was 1.4 +/- 0.04 mg/dL. However, no
      significant difference was observed in the incidence of postoperative
      complications among the hypophosphatemia groups. The phosphorus level was
      positively correlated with the remnant liver volume (r = 0.389, P < 0.001), but
      it was negatively correlated with a postoperative increase in the ALP (r = 
      0.276, P = 0.014). CONCLUSIONS: Hypophosphatemia developed very frequently after
      LDRH. However, transient hypophosphatemia was unlikely to lead to severe
      complications in healthy donors. Therefore, based on the serum level, oral or
      intravenous phosphorus replacement treatment might be more appropriate than
      routine aggressive replacement by TPN. In addition, although the factors
      responsible for posthepatectomy hypophosphatemia have not been identified, they
      might be substances that are associated with hepatic regeneration.

PMID- 18707045
TI  - 99MTc-sestamibi as sole technique in selection of primary hyperparathyroidism
      patients for unilateral neck exploration.
AB  - BACKGROUND: Unilateral neck exploration (UNE) is becoming the procedure of choice
      for treatment of primary hyperparathyroidism (PHPT). The aim of this study was to
      evaluate the role of (99m)Tc-sestamibi (MIBI) parathyroid scintigraphy as the
      sole technique in selecting patients for UNE. METHOD: We selected 136 consecutive
      PHPT patients who had only 1 solitary uptake at a MIBI were for UNE. The
      technique was a single dual-phase using MIBI and a subtraction technique with
      (99m)Tc-pertechnetate. Imaging data were correlated with surgical results.
      RESULTS: In 3 cases, the sestamibi scan was falsely positive, 1 had a
      contralateral location relative to the uptake, and 2 had multiglandular
      hyperplasia. Overall, the positive predictive value (PPV) of MIBI for detecting a
      solitary parathyroid adenoma in patients with 1 solitary uptake was 97.8. Sixteen
      patients (12%) had evidence of multinodular goiter. Overall, the PPV of MIBI was
      98.4% (2 false positive among 120 cases) in patients with no multinodular thyroid
      disease (MNG) and 93.7% (1 false negative among 16 cases) in patients with MNG.
      The mean duration of the surgical procedure was 34.17 minutes. Mean
      hospitalization was 0.6 days. Conversion to bilateral neck exploration was
      performed in 5 patients. After a period of follow-up of 40 months (range, 6-72
      months), the cure rate was 98%. CONCLUSION: Patients with PHPT and unequivocally
      positive preoperative (99m)Tc-sestamibi can safely be managed with UNE without
      additional localizing techniques.

PMID- 18707046
TI  - A proposed staging system for rectal carcinoid tumors based on an analysis of
      4701 patients.
AB  - BACKGROUND: The lack of a clinically relevant staging system for carcinoid tumors
      of the rectum creates a persistent challenge for clinicians trying to provide
      patients with meaningful prognostic information. The purpose of this study was to
      identify the clinicopathologic factors that affect survival for patients
      diagnosed with carcinoid of the rectum, and to use this information to create a
      staging system. METHODS: A search of 15,983 patients with carcinoid tumors from
      the National Cancer Institute's SEER (Surveillance Epidemiology and End Results)
      database identified 4701 patients with rectal carcinoid tumors from 1973 to 2004.
      Patients were analyzed according to various clinicopathologic factors and a tumor
      (T1, T2, T3), lymph node (N0, N1), and metastasis (M0, M1) staging system was
      created according to these parameters. The staging system was developed using log
      rank tests and the Cox proportional hazards model. RESULTS: Of the 4701 patients,
      2329 females and 2372 males were identified with a median age of 56 years (14
      94). Median size of primary tumor was 0.6 cm (0.1-25). Lymph node metastasis was
      found in 111 (4%), and distant metastatic disease was present in 97 (2.4%)
      patients. Rectal carcinoid was the only primary malignancy in 82% of patients;
      17% presented with 1 additional primary malignancy, and 1% had two or more
      additional malignancies. Age, size, depth of invasion, lymph node involvement,
      and distant metastasis were significant predictors of survival. Four stages were
      created according to statistically significant prognostic factors: 83% of
      patients were classified into Stage I, 6.5% into Stage II, 2.8% into Stage III,
      and 7.4% into Stage IV. Five-year survival rates were 97%, 84%, 27%, and 20% for
      Stages I through IV, respectively. CONCLUSION: The newly developed TNM staging
      system accurately discriminates prognosis for carcinoid tumors of the rectum.
      Size of primary tumor, depth of invasion, lymph node involvement, and distant
      metastasis have the greatest impact on survival. Incorporation of this staging
      system into clinical practice will allow better study of outcomes and development
      of stage-specific treatment recommendations.

PMID- 18707047
TI  - Racial trends in mammography rates: a population-based study.
AB  - BACKGROUND: The rates of mammography have been declining over the last 5 years.
      The objective of this study was to examine racial disparities in this trend.
      METHODS: The National Health Interview Survey is a population-based interview
      survey conducted annually. Caucasian and African-American women over 40 years of
      age who completed the cancer module of this survey in 2000 and 2005 formed the
      cohort of interest for this study. RESULTS: In 2000, 69.8% of Caucasian and 64.4%
      of African-American women over the age of 40 had had a mammogram within the
      preceding 2 years. In 2005, these rates declined to 66.7% and 62.9% respectively.
      This decline only reached statistical significance in the Caucasian population (P
      = .0006 vs P = .4998). While on univariate analysis a significant difference was
      seen between rates of mammography in Caucasian and African-American women (P <
      .0001), multivariate analysis controlling for education, income, and insurance
      status, did not find race to be a significant independent predictor of
      mammography rates in each year. CONCLUSION: Rates of mammography are declining,
      particularly in Caucasian populations. While minority women are less likely to
      report having had a mammogram, this apparent racial disparity is explained by
      differences in education, income and insurance status.

PMID- 18707048
TI  - Mesenteric and omental amyloidosis mimicking intraperitoneal carcinomatosis.

PMID- 18707049
TI  - Symptomatic accessory spleen.

PMID- 18707050
TI  - The modified technique of duodenum-preserving pancreatic head resection should
      perhaps be referred to as the Berne-Farkas modification.

PMID- 18707052
TI  - Screening for success.

PMID- 18707056
TI  - The purine machine scores a base hit.
AB  - A new synthetic method allows incorporation of 13C or 15N into selected positions
      within purine nucleotide bases, starting from simple labeled precursors. The
      procedure harnesses diverse enzymes to support biosynthesis by the pentose
      phosphate and de novo purine pathways. Selective isotope incorporation should
      expand the range of RNAs that are amenable to NMR analysis.

PMID- 18707058
TI  - Raman spectroscopy of the mixtures (x)1-butyl-1-methylpyrrolidinium chloride-(1 -
      x)TaCl5 in solid and molten states.
AB  - A series of novel ionic liquids consisting of 1-butyl-1-methylpyrrolidinium
      chloride (Pyr14Cl) and TaCl5 were obtained in a wide range of molar compositions
      for electrochemical application. Raman spectroscopy was used to investigate the
      complex formation of tantalum(V) in the mixtures of (x)Pyr14Cl-(1 - x)TaCl5 (x =
      0.80-0.30) over the temperature range 20-160 degrees C. Depending on the molar
      composition, different species of tantalum (V) were identified. In the basic and
      neutral mixtures of (x)Pyr14Cl-(1 - x)TaCl5 (x = 0.80-0.50), tantalum(V) exists
      in the form of octahedral [TaCl6](-) in both solid and molten states. In acidic
      ionic liquids (x = 0.45-0.30), [Ta2Cl10] units are the main species of
      tantalum(V) identified in the solid state. As the temperature rose, the gradual
      degradation of [Ta2Cl10] units was observed in the solid state, accompanied by
      the formation of [TaCl6](-) and [Ta2Cl11](-) anions. In the molten state, in the
      range between 130 and 160 degrees C, the latter two species exist in equilibrium
      and are the dominant species of tantalum(V). The formation of oxochloride species
      of tantalum(V) was investigated in mixtures of Pyr14Cl-TaCl5-Na2O (x = 0.65) at
      various O/Ta mole ratios, and the formation of the oligomeric species with Ta-O
      Ta bridging bonds was determined.

PMID- 18707057
TI  - Pathway engineered enzymatic de novo purine nucleotide synthesis.
AB  - A general method for isotopic labeling of the purine base moiety of nucleotides
      and RNA has been developed through biochemical pathway engineering in vitro. A
      synthetic scheme was designed and implemented utilizing recombinant enzymes from
      the pentose phosphate and de novo purine synthesis pathways, with regeneration of
      folate, aspartate, glutamine, ATP, and NADPH cofactors, in a single-pot reaction.
      Syntheses proceeded quickly and efficiently in comparison to chemical methods
      with isolated yields up to 66% for 13C-, 15N-enriched ATP and GTP. The scheme is
      robust and flexible, requiring only serine, NH4+, glucose, and CO2 as
      stoichiometric precursors in labeled form. Using this approach, U-13C- GTP, U
      13C, 15N- GTP, 13C 2,8- ATP, and U-15N- GTP were synthesized on a millimole
      scale, and the utility of the isotope labeling is illustrated in NMR spectra of
      HIV-2 transactivation region RNA containing 13C 2,8-adenosine and 15N 1,3,7,9,2
      guanosine. Pathway engineering in vitro permits complex synthetic cascades to be
      effected, expanding the applicability of enzymatic synthesis.

PMID- 18707059
TI  - The infrared spectrum of solid L-alanine: influence of pH-induced structural
      changes.
AB  - The influence of the pH on the infrared spectrum of L-alanine has been analyzed
      by diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy. The amino
      acid was precipitated from aqueous solutions and dried at 36.5 degrees C, in
      order to stabilize cationic L-alanine or alaninium [CH3CH(NH3(+))COOH] at pH 1,
      the zwitterionic form [CH3CH(NH3(+))COO(-)] at pH 6, and anionic L-alanine or
      alaninate [CH3CH(NH2)COO(-)] at pH 13. New insight on the specific inter and
      intramolecular interactions in the different forms of L-alanine was reached by a
      novel methodological approach: an infrared technique not used before to analyze
      solid amino acid samples (DRIFTS), in combination with a detailed analysis based
      on spectral deconvolution. The frequency ranges of interest include the
      carbonyl/carboxyl stretching and amine deformation modes and the OH/NH stretching
      modes. It was shown that intermolecular hydrogen bonds between the NH3(+) and
      COO(-) groups are predominant in the zwitterionic form, whereas in cationic L
      alanine, H bonds between the COOH groups are responsible for the formation of
      dimers. In anionic L-alanine, only strong electrostatic interactions between the
      COO(-) groups and Na(+) ions are proposed, evidencing the relevant role of the
      counterion.

PMID- 18707060
TI  - Probing the dependence of long-range, four-atom interactions on intermolecular
      orientation: 2. Molecular deuterium and iodine monochloride.
AB  - Laser-induced fluorescence and action spectroscopy experiments have identified
      multiple conformers of the D2...ICl van der Waals complex for both ortho-D2 (o
      D2) and para-D2 (p-D2). As with the analogous H2...ICl van der Waals complexes
      [Darr, J. P.; Crowther, A. C.; Loomis, R. A.; Ray, S. E.; McCoy, A. B. J. Phys.
      Chem. A 2007, 111, 13387], the C2v conformer with the deuterium molecule
      localized at the iodine atom end of the dihalogen is significantly more stable
      than the asymmetric conformer that has the deuterium positioned orthogonally to
      the ICl bond axis, D0'' = 223.9(2.4) versus 97.3(8)-103.9(3) cm(-1) for p
      D2...I(35)Cl(X, v''=0). For both conformers, complexes containing p-D2 are found
      to be more strongly bound than those with o-D2. The electronically excited
      D2...ICl(A, v') and D2...ICl(B, v') complexes are found to have equilibrium
      geometries that are nearly the same as those of the ground-state asymmetric
      structures. Calculated D2...ICl(B, v'=3) energies and probability amplitudes
      obtained using a simple scaled He + ICl(B, v'=3) potential provide clues to the
      nature of the different excited-state levels accessed.

PMID- 18707061
TI  - Validation of dispersion-corrected density functional theory approaches for ionic
      liquid systems.
AB  - The performance of several general gradient approximation, meta general gradient
      approximation, and hybrid functionals is tested against Moller-Plesset
      perturbation theory second-order for ionic liquid systems. Additionally, two
      dispersion-corrected approaches (addition of van der Waals forces by a 1/r(6)
      term and employing a dispersion-corrected atom-center dispersion pseudopotential)
      were studied. For the 1-butyl-3-methylimidazolium cation neglecting dispersion
      results in different trends for structural stabilities. The two applied
      correction schemes for density functional theory improve the results
      tremendously. Investigating several 1-butyl-3-methylimidazolium dicianamide ion
      pairs shows a mean absolute deviation from Moller-Plesset perturbation theory of
      35.7 kJ/mol for Hartree-Fock and up to 33.2 kJ/mol for the density functional
      theory methods. The dispersion-corrected methods reduce the mean absolute
      deviation to less than 10 kJ/mol. Comparing adducts of the 1-ethyl-3
      methylimidazolium dicianamide ion pair with Diels-Alder educts (cyclopentadiene
      and methylacrylate) shows similar energetic differences as for the ion pairs.
      Furthermore large deviations in geometries for the intermolecular distances were
      found for the Hartree-Fock approach (mean absolute deviation: 190 pm) and density
      functional theory (mean absolute deviation up to 178 pm) while for the dispersion
      corrected methods the mean absolute deviation is less than 50 pm.

PMID- 18707062
TI  - Femtosecond dynamics of piroxicam structures in solutions.
AB  - We report on studies of femtosecond dynamics of a nonsteroidal anti-inflammatory
      drug, piroxicam (1), in water at three different pHs and for comparison in two
      aprotic solvents. An ultrafast excited-state proton-transfer (ESIPT) process
      takes place in neutral and cationic enol-type structures. Femtosecond emission
      and transient absorption experiments show that this reaction is barrierless, and
      the proton-transferred keto tautomer is formed in less than 100 fs in both
      organic solvents and acidic water. In neutral and alkaline water, the ESIPT is
      not present because of the prevalence of the anion structures at the ground
      state. For the excited anions (pH = 7, 11) and formed keto cations (pH
      approximately 3), an intramolecular charge-transfer process takes place in times
      shorter than 0.3 ps. The formed structures have a fluorescence lifetime of
      approximately 2-5 ps, depending on pH. In contrast, the internal twisting motion
      in organic solvents is slower (approximately 0.5-1 ps) and gives rotamers with
      lifetimes of tens of picoseconds. These results clearly show strong interactions
      of 1 with water, significantly distinct from those present in organic aprotic
      solvents. We believe that the results are important for a better understanding on
      short time interactions of drugs with their environment.

PMID- 18707063
TI  - A combined spectroscopic and theoretical study of dibutyltin diacetate and
      dilaurate in supercritical CO2.
AB  - Two organotin catalysts, namely, dibutyltin dilaurate (DBTDL) and dibutyltin
      diacetate (DBTDA), commonly used in the synthesis of polyurethanes, have been
      investigated combining vibrational spectroscopic measurements with molecular
      modeling. The structure and vibrational spectra of the DBTDA molecule have been
      simulated using density functional theory. Thus, because of the Sn...O
      interactions, the lowest energy conformer reveals an asymmetrically chelated
      structure of the acetate groups with a C2v symmetry. The experimental IR spectra
      of DBTDA and DBTDL diluted in carbon tetrachloride and in supercritical CO2 show
      unambiguously that these molecules adopt the asymmetrically chelated conformation
      in the solvent. A new attribution of the main peaks constituting the respective
      IR spectra of the catalysts could be carried out. Finally, from the IR spectra of
      the two catalysts diluted in supercritical CO2 reported as a function of time, it
      was found that both molecules react slightly with CO2. However, their spectrum
      remains unchanged at the earliest stage of the polymerization, indicating that
      these molecules preserve a catalytic activity similar to that noted in
      conventional organic solvent.

PMID- 18707064
TI  - Kinetics of the OH + ClOOCl and OH + Cl2O reactions: experiment and theory.
AB  - The rate coefficients for the reactions OH + ClOOCl --> HOCl + ClOO (eq 5) and OH
      + Cl2O --> HOCl + ClO (eq 6) were measured using a fast flow reactor coupled with
      molecular beam quadrupole mass spectrometry. OH was detected using resonance
      fluorescence at 309 nm. The measured Arrhenius expressions for these reactions
      are k5 = (6.0 +/- 3.5) x 10(-13) exp((670 +/- 230)/T) cm(3) molecule(-1) s(-1)
      and k6 = (5.1 +/- 1.5) x 10(-12) exp((100 +/- 92)/T) cm(3) molecule(-1) s(-1),
      respectively, where the uncertainties are reported at the 2sigma level.
      Investigation of the OH + ClOOCl potential energy surface using high level ab
      initio calculations indicates that the reaction occurs via a chlorine abstraction
      from ClOOCl by the OH radical. The lowest energy pathway is calculated to proceed
      through a weak ClOOCl-OH prereactive complex that is bound by 2.6 kcal mol(-1)
      and leads to ClOO and HOCl products. The transition state to product formation is
      calculated to be 0.59 kcal mol(-1) above the reactant energy level. Inclusion of
      the OH + ClOOCl rate data into an atmospheric model indicates that this reaction
      contributes more than 15% to ClOOCl loss during twilight conditions in the Arctic
      stratosphere. Reducing the rate of ClOOCl photolysis, as indicated by a recent re
      examination of the ClOOCl UV absorption spectrum, increases the contribution of
      the OH + ClOOCl reaction to polar stratospheric loss of ClOOCl.

PMID- 18707065
TI  - Theoretical studies of blue-emitting iridium complexes with different ancillary
      ligands.
AB  - The structural and electronic properties of two heteroleptic iridium complexes
      Ir(dfppy)2(pic) (FIrpic) and Ir(dfppy)2(acac) (FIracac) have been investigated
      theoretically, where dfppy = 2-(2,4-difluorophenyl) pyridine, pic = picolinic
      acid, and acac = acetoylacetonate. The geometries of ground and excited states
      are optimized at PBE0/LANL2DZ and CIS/LANL2DZ levels, respectively. Time
      dependent density functional theory (TDDFT) method is employed to explore the
      absorption and emission properties. In the ground state, the highest-occupied
      molecular orbital has a significant mixture of metal Ir(d) and dfppy(pi), the
      lowest-unoccupied orbital locates primarily on pi* of pic for FIrpic and pi* of
      dfppy for FIracac. The luminescence of each complex originates from the lowest
      triplet excited state, which is assigned to the mixing of metal-to-ligand charge
      transfer and intraligand charge transfer characters. The effects of ancillary
      ligands pic and acac on absorption and emission spectra are observed by analysis
      of TDDFT results. The connection between the nature of excited states and the
      behavior of the complexes with different ancillary ligands is elucidated.

PMID- 18707066
TI  - Disproportionation pathways of aqueous hyponitrite radicals (HN2O2(*)/N2O2(*-)).
AB  - Pulse radiolysis and flash photolysis are used to generate the hyponitrite
      radicals (HN2O2(*)/N2O2(*-)) by one-electron oxidation of the hyponitrite in
      aqueous solution. Although the radical decay conforms to simple second-order
      kinetics, its mechanism is complex, comprising a short chain of NO release
      consumption steps. In the first, rate-determining step, two N2O2(*-) radicals
      disproportionate with the rate constant 2k = (8.2 +/- 0.5) x 10(7) M(-1) s(-1)
      (at zero ionic strength) effectively in a redox reaction regenerating N2O2(2-)
      and releasing two NO. This occurs either by electron transfer or, more likely,
      through radical recombination-dissociation. Each NO so-produced rapidly adds to
      another N2O2(*-), yielding the N3O3(-) ion, which slowly decomposes at 300 s(-1)
      to the final N2O + NO2(-) products. The N2O2(*-) radical protonates with pKa =
      5.6 +/- 0.3. The neutral HN2O2(*) radical decays by an analogous mechanism but
      much more rapidly with the apparent second-order rate constant 2k = (1.1 +/- 0.1)
      x 10(9) M(-1) s(-1). The N2O2(*-) radical shows surprisingly low reactivity
      toward O2 and O2(*-), with the corresponding rate constants below 1 x 10(6) and 5
      x 10(7) M(-1) s(-1). The previously reported rapid dissociation of N2O2(*-) into
      N2O and O(*-) does not occur. The thermochemistry of HN2O2(*)/N2O2(*-) is
      discussed in the context of these new kinetic and mechanistic results.

PMID- 18707067
TI  - Photophysics and deactivation pathways of thymine.
AB  - Combined complete active space perturbation theory (CASPT2) and multireference
      configuration interaction calculations with single and double excitations (MR
      CISD) were performed in order to explore possible deactivation pathways of
      thymine after photoexcitation. Equilibrium geometries are reported together with
      a total of eight extremes (minima or maxima) on the crossing seam (MXS), through
      which such radiationless transitions may occur. Furthermore, conformational
      analysis allows grouping these conical intersections in five distinct types.
      Reaction paths were calculated connecting the S1 (1)n pi* minimum with the lowest
      energy MXS of each group. Two distinct types of paths were observed, both with
      features that should delay the internal conversion to the ground state. This is
      shown to provide a possible explanation for the relatively long excited-state
      lifetime of thymine.

PMID- 18707069
TI  - Vibrational contributions to indirect spin-spin coupling constants calculated via
      variational anharmonic approaches.
AB  - Zero-point vibrational contributions to indirect spin-spin coupling constants for
      N2, CO, HF, H2O, C2H2, and CH4 are calculated via explicitly anharmonic
      approaches. Thermal averages of indirect spin-spin coupling constants are
      calculated for the same set of molecules and for C2X4, X = H, F, Cl. Potential
      energy surfaces have been calculated on a grid of points and analytic
      representations have been obtained by a linear least-squares fit in a direct
      product polynomial basis. Property surfaces have been represented by a fourth
      order Taylor expansion around the equilibrium geometry. The electronic structure
      calculations employ density functional theory, and vibrational contributions to
      indirect spin-spin coupling constants are calculated employing vibrational self
      consistent-field and vibrational configuration-interaction methods. The
      performance of vibrational perturbation theory and various approximate
      variational calculations are discussed. Thermal averages are computed by state
      specific and virtual vibrational self-consistent-field methods.

PMID- 18707068
TI  - A computational characterization of boron-oxygen multiple bonding in HN=CH-CH=CH
      NH-BO.
AB  - Structures, relative energies, and bonding characteristics for various conformers
      of 3-imino-N-(oxoboryl)prop-1-en-1-amine, HN=CH-CH=CH-NH-BO, and the
      corresponding borocycle (-HN=CH-CH=CH-NH-B-)O are discussed using results from
      second-order Moller-Plesset (MP2) perturbation theory with the Dunning-Woon
      correlation-consistent cc-pVDZ, aug-cc-pVDZ, and cc-pVTZ basis sets. These MP2
      results are compared to those from computationally efficient density functional
      theory (DFT) calculations using the LDA, PBE, TPSS, BLYP, B3LYP, BVP86, OLYP,
      O3LYP, and PBE1PBE functionals in conjunction with the economical Pople-type 6
      311++G(d,p) basis set to evaluate the suitability of these DFT/6-311++G(d,p)
      levels for use with larger boron-containing systems. The effects of an aqueous
      environment were incorporated into the calculations using COSMO methodology. The
      calculated boron-oxygen bond lengths, orbital compositions, and bond orders in
      all the (acyclic) HN=CH-CH=CH-NH-BO conformers were consistent with the presence
      of a boron-oxygen triple bond, similar to that found in H-BO and H2N-BO. The (
      HN=CH-CH=CH-NH-B-)O borocycle is predicted to be planar (C2v symmetry), and it is
      approximately 30 kcal/mol lower in energy than any of the (acyclic) HN=CH-CH=CH
      NH-BO conformers; the boron-oxygen bond in this borocycle has significant double
      bond character, a bonding scheme for which there has been only one experimental
      structure reported in the literature (Vidovic, D. ; et al. J. Am. Chem. Soc.
      2005, 127, 4566- 4569).

PMID- 18707070
TI  - The HSSS radical and the HSSS- anion.
AB  - The HS3 radical and the HS3(-) anion, the sulfur analogues of HO3 and HO3(-),
      have been detected for the first time by mass spectrometric experiments performed
      in the gas phase. The structural and energetic features of HS3 and HS3(-) have
      been investigated by ab initio calculations. Both HS3 and HS3(-) are
      characterized by HSSS open-chain structures, stable toward the dissociation into
      S2 and HS(0/-). HS3 adds to HS and HS2 as the known HS n species, and HS3(-) is
      the conjugate base of a strong Bronsted acid, the trisulfane HSSSH.

PMID- 18707071
TI  - New insight into photochemistry of ferrioxalate.
AB  - Optical spectroscopy and nanosecond flash photolysis (Nd:YAG laser, 355 nm, pulse
      duration 5 ns, mean energy 5 mJ/pulse) were used to study the photochemistry of
      Fe(III)(C2O4)3(3-) complex in aqueous solutions. The main photochemical process
      was found to be intramolecular electron transfer from the ligand to Fe(III) ion
      with formation of a primary radical complex [(C2O4)2Fe(II)(C2O4(*))](3-). The
      yield of radical species (i.e., CO2(*-) and C2O4(*-)) was found to be less than
      6% of Fe(III)(C2O4)3(3-) disappeared after flash. [(C2O4)2Fe(II)(C2O4(*))](3-)
      dissociates reversibly into oxalate ion and a secondary radical complex,
      [(C2O4)Fe(II)(C2O4(*))](-). The latter reacts with the initial complex and
      dissociates to Fe(II)(C2O4) and oxalate radical. In this framework, the
      absorption spectra and rate constants of the reactions of all intermediates were
      determined.

PMID- 18707072
TI  - Consequences of strong coupling between solvation and electronic structure in the
      excited state of a betaine dye.
AB  - The electronic ground and excited-state structures of the betaine dye molecule
      pyridinium- N-phenoxide [4-(1-pyridinio)phenolate] are investigated both in the
      gas phase and in aqueous solution, using the reference interaction site model
      self-consistent-field (RISM-SCF) procedure within a CASSCF framework. We obtain
      the total free energy profiles in both the ground and excited states with respect
      to variation in the torsion angle between the phenoxide and pyridinium rings. We
      analyze the effect of solvent on the variation of the solute dipole moment and on
      the charge transfer character in the excited state. In the gas phase, it is shown
      that the potential energy profile in the excited-state decreases monotonically
      toward a perpendicular ring orientation and the dipole moment decreases along
      with decreasing charge localization. In water, the free energy surface for
      twisting is better characterized as nearly flat along the same coordinate for
      sterically accessible angles. These results are analyzed in terms of
      contributions of the solvation free energy, the solute electronic energy, and
      their coupling. Correspondingly, the dependence of the charge transfer character
      on solute geometry and solvation are analyzed, and the important roles in the
      excitation and subsequent relaxation processes for the betaine dye are discussed.
      It is found that there is considerable solute electronic reorganization
      associated with the evolution of solvation in the excited state, and it is
      suggested that this reorganization may contribute significantly to the early time
      evolution of transient spectra following photoexcitation.

PMID- 18707073
TI  - Preparation of ferrite MFe2O4 (M = Co, Ni) ribbons with nanoporous structure and
      their magnetic properties.
AB  - Spinel ferrite, MFe 2O 4 (M = Co, Ni), ribbons with nanoporous structure were
      prepared by electrospinning combined with sol-gel technology. The ribbons were
      formed through the agglomeration of magnetic nanoparticles with PVP as the
      structure directing template. The length of the polycrystalline ribbons can reach
      millimeters, and the width of the ribbons can be tuned from several micrometers
      to several hundred nanometers by changing the concentration of precursor. The
      nanoporous structure was formed during the decomposition of PVP and inorganic
      salts. The ribbons exhibited weak saturation magnetizations and low coercivities
      at room temperature, but at low temperature, saturation magnetizations and
      coercivities increased a lot, especially for CoFe 2O 4 ribbons, reaching 72 emu/g
      and 1.45 T at 2 k, respectively. These novel magnetic ribbons can potentially be
      used in micro/nano electronic devices, gas-sensors, and catalysts.

PMID- 18707074
TI  - Effects of double-layer polarization and electroosmotic flow on the
      electrophoresis of an ellipsoid in a spherical cavity.
AB  - The electrophoresis of a rigid, positively charged ellipsoidal particle at the
      center of a spherical cavity is investigated theoretically under the conditions
      where the effects of double-layer polarization and the presence of an
      electroosmotic flow can be important. The equations governing the problem under
      consideration and the associated boundary conditions are solved numerically, and
      the influences of the key parameters on the electrophoretic mobility of the
      particle are discussed. We show that if the cavity is uncharged, the effect of
      double-layer polarization yields a local minimum in the electrophoretic mobility
      as the thickness of the double layer varies. This local minimum disappears if the
      cavity is also positively charged. In addition to reducing the scaled mobility of
      an ellipsoid, the presence of the boundary is also capable of influencing the
      relative magnitudes of the scaled mobility for particles of various shapes. For
      instance, if the volume of an ellipsoid is fixed, the scaled mobility ranks as
      prolate > sphere > oblate if the boundary effect is unimportant, but that order
      is reversed if the boundary effect is important.

PMID- 18707075
TI  - Effects of salt and nanoparticles on the segmental motion of poly(ethylene oxide)
      in its crystalline and amorphous phases: 2H and 7Li NMR studies.
AB  - We use (2)H NMR to investigate the segmental motion of poly(ethylene oxide) (PEO)
      in neat and nanocomposite materials that do and do not contain salt.
      Specifically, in addition to a neat low-molecular-weight PEO, we study mixtures
      of this polymer with TiO 2 nanoparticles and LiClO 4. To characterize the polymer
      dynamics over a wide range of time scales, we combine (2)H NMR spin-lattice
      relaxation, line-shape, and stimulated-echo analyses. The results consistently
      show that the presence of nanoparticles hardly affects the behavior of the
      polymer, while addition of salt leads to substantial changes; e.g., it reduces
      the crystallinity. For neat PEO and a PEO-TiO 2 mixture, stimulated-echo
      spectroscopy enables measurement of rotational correlation functions for the
      crystalline phase. Analysis of the decays allows us to determine correlation
      times, to demonstrate the existence of a nonexponential relaxation, which implies
      a high complexity of the polymer dynamics in the crystal, and to show that the
      reorientation can be described as a large-angle jump. For a PEO-TiO 2-LiClO 4
      mixture, we use (2)H and (7)Li NMR to study the polymer and the lithium dynamics,
      respectively. Analysis of the (7)Li spin-lattice relaxation reveals a high
      lithium ionic mobility in this nanocomposite polymer electrolyte. The (7)Li
      stimulated-echo decay is well described by a stretched exponential extending over
      about 6 orders of magnitude, indicating that a broad and continuous distribution
      of correlation times characterizes the fluctuations of the local lithium ionic
      environments.

PMID- 18707076
TI  - Ammonium nitrate-polymer glasses: a new concept for phase and thermal
      stabilization of ammonium nitrate.
AB  - Dissolving of ammonium nitrate in highly polar polymers such as
      poly(vinylpyrrolidone) and/or poly(acrylamide) can result in the formation of
      single-phase glassy solid materials, in which NH 4 (+) and NO 3 (-) are separated
      through an ion-dipole interaction with the polymer matrix. Below the glass
      transition temperature of the polymer matrix the resulting materials remain phase
      and thermally stable as demonstrated through the absence of decomposition as well
      as the solid-solid transitions and melting of ammonium nitrate. The structure of
      the materials is explored by Fourier transform infrared spectroscopy and density
      functional calculations. Differential scanning calorimetry, thermogravimetry, and
      isoconversional kinetic analysis are applied to characterize the thermal behavior
      of the materials.

PMID- 18707077
TI  - Separation and analysis of dynamic Stokes shift with multiple fluorescence
      environments: coumarin 153 in bovine beta-lactoglobulin A.
AB  - We use time-dependent fluorescence Stokes shift (TDFSS) information to study the
      fluctuation rates of the lipocalin, beta-lactoglobulin A in the vicinity of an
      encapsulated coumarin 153 molecule. The system has three unique dielectric
      environments in which the fluorophore binds. We develop a method to decompose the
      static and dynamic contributions to the spectral heterogeneity. This method is
      applied to temperature-dependent steady-state fluorescence spectra providing us
      with site-specific information about thermodynamic transitions in beta
      lactoglobulin. We confirm previously reported transitions and discuss the
      presence of an unreported transition of the central calyx at 18 degrees C. Our
      method also resolves the contributions to the TDFSS from the coumarin 153
      centrally located in the calyx of beta-lactoglobulin despite overlapping signals
      from solvent exposed dyes. Our experiments show dynamics ranging from 3-12,00 ps.
      The analysis shows a decrease in the encapsulated dye's heterogeneity during the
      relaxation, which is taken as evidence of the breakdown of linear response.

PMID- 18707078
TI  - Frictional properties of surfactant-coated rod-shaped nanoparticles in dry and
      humid dodecane.
AB  - We have investigated the effects of humidity (water content or activity from 0 to
      approximately 0.98) on the frictional properties of surfactant-coated ZnS
      nanoparticles of various shapes, specifically, nanorods and nanowires, dispersed
      in an organic solvent (dodecane). The friction coefficients were found to be
      sensitive to even trace amounts of water, increasing logarithmically with time
      after the systems were exposed to humid air, doubling after 2-4 h of exposure
      time to air of relative humidity approximately 98%. We also show that increasing
      the humidity caused noticeable effects on the interactions of the nanoparticles,
      increasing their adhesion and aggregation through capillary forces. These effects
      should be considered in the design of organic solvents containing nanoparticles
      with physisorbed surfactants, for example, lube oils with nanoparticles
      additives, particularly those exposed to atmospheric conditions.

PMID- 18707079
TI  - Stacking of 2,3,5-triphenyl-2H-tetrazolium chloride onto polyelectrolytes
      containing 4-styrenesulfonate groups.
AB  - Possible structural aspects are discussed that justify the different resistance
      to reduction of 2,3,5-triphenyl-2 H-tetrazolium chloride (TTC) both chemically
      (by reaction with ascorbic acid (ASC)) and electrochemically, in the presence of
      different polyelectrolytes such as poly(sodium 4-styrenesulfonate) (PSS),
      poly(sodium 4-styrenesulfonate- co-sodium maleate) at two different comonomer
      compositions (P(SS 1- co-MA 1) and P(SS 3- co-MA 1)), and poly(sodium acrylate-
      co-sodium maleate) (P(AA 1- co-MA 1)). Different dissociation constants are found
      for the complexes between TTC and the different polyelectrolytes by diafiltration
      (DF). Related to this, spectroscopical differences are also found by (1)H NMR and
      UV-vis spectroscopies. Dynamic light scattering (DLS) showed a higher tendency to
      undergo intermolecular aggregation for P(SS 1- co-MA 1) in the presence of TTC, a
      result that could be related with a higher tendency for TTC to form hydrophobic
      ion pairs as a consequence of single stacking with the benzene sulfonate groups
      (BS) of this polyelectrolyte. On the other hand, the lower tendency for PSS to
      undergo intermolecular aggregation could be attributable to a higher probability
      to form more hydrophilic adducts by means of double stacking with TTC.

PMID- 18707080
TI  - Mixing schemes in a urea-H2O system: a differential approach in solution
      thermodynamics.
AB  - The excess partial molar enthalpies of urea (UR), H U R (E ), were experimentally
      determined in UR-H 2O at 25 degrees C. The H U R (E ) data were determined
      accurately and in small increments in the mole fraction of UR, x U R , up to x U
      R approximately 0.22. Hence it was possible to evaluate one more x U R 
      derivative graphically without resorting to any fitting function, and the model
      free UR-UR enthalpic interaction, H U R- U R (E ), was calculated. Using previous
      data for the excess chemical potential, mu U R (E ), the entropy analogue, S U R-
      U R (E ), was also calculated. The x U R -dependences of both H U R- U R (E ) and
      S U R- U R (E ) indicate that there is a boundary at x U R approximately 0.09 at
      which the aggregation nature of urea changes. From the results of our earlier
      works, we suggest that a few UR molecules aggregate at x U R approximately 0.09,
      while the integrity of H 2O is retained at least up to x U R approximately 0.20.
      Together with the findings from our previous studies, we suggest that in the
      concentration range x U R < 0.22, UR or its aggregate form hydrogen bonds to the
      H 2O network, reducing the degree of fluctuation characteristic to liquid H 2O.
      However, up to at least x U R = 0.20 the hydrogen bond network remains intact.
      Above x U R approximately 0.22, the integrity of H 2O is likely be lost. Thus, in
      discussing the effect of urea on H 2O and in relating it to the structure and
      function of biopolymers in aqueous solutions, the concentration region in
      question must be specified.

PMID- 18707081
TI  - Measurements and predictive models for the N-methyl-2-pyrrolidone/water/methanol
      system.
AB  - This work reports on the properties and structure of N-methyl-2-pyrrolidone in
      binary and ternary liquid mixtures with water and/or methanol. A comprehensive
      set of thermophysical properties have been measured at 298.15 K and 0.1 MPa over
      the whole composition range. On the basis of the derived excess and mixing
      properties, the fluid structure was analyzed by looking into the forces and
      geometry factors that effectively control the mixture behavior. Application of
      the inverted Kirkwood-Buff theory provides a reasonable link between the
      macroscopic properties and the microscopic features. A density functional theory
      computation was carried out to analyze the structure and energy features of the
      hydrogen bonded complexes formed between the components. Use of semiempirical
      models in the framework of molecular-based equations of state according to the PC
      SAFT approach led to unsatisfactory predicted thermophysical properties. The
      conclusions arrived at give away the existence of strong heteroassociations and
      hydrogen bonding self-associations that determine the complex nature of the fluid
      structure.

PMID- 18707082
TI  - Modeling of cw-EPR spectra of propagating radicals in methacrylic polymerization
      at different temperatures.
AB  - The temperature dependence of the cw-EPR spectra corresponding to the propagating
      radical responsible for the polymerization of methacrylic monomers has been
      simulated by an integrated computational approach that determines the structural
      and magnetic parameters (via quantum mechanical calculations) and diffusive
      properties (via hydrodynamic based methods), which represent the overall input of
      the stochastic Liouville equation that yields the spectrum. The system has been
      modeled as a rotator with only one relaxation process, the rotation around the C
      alpha-C beta bond. The simulations clearly indicate that the change of the
      spectral shape with the temperature is essentially related to the internal
      flexibility of the radical end.

PMID- 18707083
TI  - Influence of ion transfer kinetics on the composition of langmuir-blodgett films.
AB  - The effect of ion transfer kinetics on the ionic composition of Langmuir-Blodgett
      (LB) films formed by charged monolayers is analyzed. The dynamic regimes of the
      LB deposition are considered by taking into account the competitive adsorption of
      several counterions having different diffusivities, valences, binding constants,
      and bulk concentrations. It is shown that the composition of deposited films
      should change with the deposition rate. At lower deposition rates, the ion with
      higher binding constant is more represented within the deposited monolayer in
      comparison to the higher deposition rates. At low deposition rates, the ratio of
      counterion amounts within the LB films is the same as that within the floating
      monolayer excluding the ions within the diffuse layer. At high deposition rates,
      the ratio of the counterion amounts is the same as that within the floating
      monolayer when the potential-determining counterions within the diffuse layer are
      taken into account.

PMID- 18707084
TI  - Combined emulsion and phase inversion techniques for the preparation of catalytic
      PVDF microcapsules.
AB  - In this work, polyvinilydene fluoride (PVDF) microcapsules were prepared by using
      combined emulsion and phase inversion techniques. With this method, microcapsules
      with different diameters and porosities have been obtained by just controlling
      the diameter of the membrane used during the preparation. Using a PVDF solution
      containing the oxidation catalyst ammonium molybdate (20 wt %), catalytic
      polymeric microcapsules with diameters ranging from 600 to 1,200 microm have been
      obtained. Characterization of catalytic microcapsules by means of SEM, BSE, and
      EDX analyses showed a uniform ammonium molybdate dispersion in the polymeric
      matrix. Catalytic microcapsules have been tested in the oxidation of aromatic
      primary alcohols to corresponding aldehydes. In the range 600-1,200 microm, the
      microcapsule diameter influences the formation of oxidation products: in
      particular, microcapsule diameters >900 microm slightly diminish the formation of
      aldehyde due to a beginning diffusion limitation. An interesting structure
      reactivity behavior, induced by the interaction between the polymeric membrane
      and the substituted aromatic alcohol, has been observed.

PMID- 18707085
TI  - Ultrafast vibrational dynamics of adenine-thymine base pairs in DNA oligomers.
AB  - N-H stretching excitations of DNA oligomers containing 23 alternating adenine
      thymine base pairs are studied in femtosecond two-color pump-probe experiments.
      For a DNA film in a zero relative humidity atmosphere, transient vibrational
      spectra and their time evolution up to 10 ps demonstrate negligible spectral
      diffusion and allow for discerning different N-H stretching bands and the O-H
      stretching absorption of residual water molecules. Lifetimes on the order of 0.5
      ps are found for both N-H and O-H stretching modes. The time-dependent pump-probe
      anisotropies of the different N-H excitations point to a pronounced coupling
      among them, whereas the O-H stretching anisotropy remains essentially constant.

PMID- 18707086
TI  - Chain-length dependence of diblock copolymer micellization kinetics studied by
      stopped-flow pH-jump.
AB  - A series of well-defined poly(ethylene oxide)- b-poly(2-(diethylamino)ethyl
      methacrylate) (PEO- b-PDEA) diblock copolymers containing PEO block of identical
      chain length and PDEA block with varying degrees of polymerization (DP, in the
      range of 32-154) were prepared via atom transfer radical polymerization (ATRP)
      employing a PEO-based macroinitiator (DP = 113). Upon a pH-jump from 3 to 12
      under highly efficient stopped-flow mixing conditions, PEO- b-PDEA copolymers
      spontaneously form spherical micelles of increasing sizes and aggregation numbers
      ( N agg) with increasing PDEA chain lengths. Stopped-flow light scattering
      technique was used to probe the pH-induced micellization kinetics of PEO- b-PDEA
      copolymers, aiming to elucidate the PDEA chain-length effects on the unimer-to
      micelle transition process. Upon a stopped-flow pH-jump from 3 to 12, the
      obtained dynamic traces can be well-fitted with double exponential functions. The
      calculated fast and slow characteristic relaxation times (tau 1 and tau 2) can be
      ascribed to the formation of quasi-equilibrium micelles (fast process) and
      subsequent relaxation into final equilibrium micelles (slow process),
      respectively. For PEO 113- b-PDEA 32 and PEO 113- b-PDEA 61, tau 2 is almost
      independent of polymer concentrations, suggesting that the relaxation from quasi
      equilibrium micelles into final equilibrium micelles mainly proceeds via
      insertion/expulsion of unimer chains. Upon increasing the DP of pH-responsive
      PDEA block to 89, 117, and 154, the obtained slow relaxation time, tau 2, tends
      to decrease with increasing polymer concentrations, suggesting that the slow
      process is dominated by the micelle fusion/fission mechanism. The apparent
      activation energy ( E a) associated with tau 2 has also been determined from
      temperature-dependent micellization kinetics for five PEO- b-PDEA copolymers. It
      was found that during micellization, copolymers with longer PDEA blocks exhibit
      much lower E a compared to those with shorter blocks. Thus, we observed
      experimentally for the first time that increasing the hydrophobic block length in
      double hydrophilic block copolymers (DHBCs) can transform the mechanism of the
      slow process from unimer insertion/expulsion to micelle fusion/fission.

PMID- 18707088
TI  - Conformationally constrained analogues of diacylglycerol. 30. An investigation of
      diacylglycerol-lactones containing heteroaryl groups reveals compounds with high
      selectivity for Ras guanyl nucleotide-releasing proteins.
AB  - Using a diacylglycerol-lactone (DAG-lactone) template previously developed in our
      laboratory as a scaffold with high binding affinity for C1 domains, we describe
      herein a series of novel DAG-lactones containing heterocyclic moieties
      (pyridines, quinolines, and indoles) as alpha-arylidene fragments. Some of the
      DAG-lactones obtained show selective binding to RasGRP3 as compared to PKCalpha
      by more than 2 orders of magnitude and possess subnanomolar affinities. Because
      activated C1 domains bound to their ligands (DAG or DAG-lactones) insert into
      membranes, the lipid composition of membranes (cellular, nuclear, and those of
      internal organelles) is an important determinant for specificity. Therefore,
      reaching a proper hydrophilic/lipophilic balance for these molecules is critical.
      This was achieved by carefully selecting partnering acyl fragments for the DAG
      lactones with the appropriate lipophilicity. The results clearly show that the
      combination of chemical and physical properties in these molecules needs to be
      perfectly balanced to achieve the desired specificity.

PMID- 18707087
TI  - Modulating G-protein coupled receptor/G-protein signal transduction by small
      molecules suggested by virtual screening.
AB  - Modulation of interactions between activated GPCRs (G-protein coupled receptors)
      and the intracellular (IC) signal transducers, heterotrimeric G-proteins, is an
      attractive, yet essentially unexplored, paradigm for treatment of certain
      diseases. Regulating downstream signaling for treatment of congenital diseases
      due to constitutively active GPCRs, as well as tumors where GPCRs are often
      overexpressed, requires the development of new methodologies. Modeling,
      experimental data, docking, scoring, and experimental testing (MEDSET) was
      developed to discover inhibitors that target the IC loops of activated GPCRs. As
      proof-of-concept, MEDSET developed and utilized a model of the interface between
      photoactivated rhodopsin (R*) and transducin (Gt), its G-protein. A National
      Cancer Institute (NCI) compound library was screened to identify compounds that
      bound at the interface between R* and its G-protein. High-scoring compounds from
      this virtual screen were obtained and tested experimentally for their ability to
      stabilize R* and prevent Gt from binding to R*. Several compounds that modulate
      signal transduction have been identified.

PMID- 18707089
TI  - 4"-Benzoylureido-TSAO derivatives as potent and selective non-nucleoside HCMV
      inhibitors. Structure-activity relationship and mechanism of antiviral action.
AB  - Analogues of the 4"-benzoyl-ureido-TSAO derivative (1) modified at different
      positions have been prepared and evaluated against wild-type strains of HCMV and
      murine cytomegalovirus (MCMV) in cell culture. In addition, the activity of the
      most active derivatives against several drug-resistant HCMV mutants has been
      determined. A stringent structure-antiviral activity relationship was observed
      for the 4"-benzoylureido- TSAO derivatives for which the concomitant presence of
      a highly lipophilic substituent at both 2'- and 5'-positions was required to
      fully preserve the antihuman cytomegalovirus efficacy. Time-of-addition studies
      and HCMV immediately early and early gene expression studies revealed a target at
      the time of viral DNA synthesis, although direct inhibition of HCMV-encoded DNA
      polymerase could not be observed in cell-free assays. Lack of cross-resistance
      against a broad variety of mutant HCMV strains points to an antiviral target that
      is different from those drugs that are currently approved for clinical use.

PMID- 18707090
TI  - Novel glucagon receptor antagonists with improved selectivity over the glucose
      dependent insulinotropic polypeptide receptor.
AB  - Optimization of a new series of small molecule human glucagon receptor (hGluR)
      antagonists is described. In the process of optimizing glucagon receptor
      antagonists, we counter-screened against the closely related human gastric
      inhibitory polypeptide receptor (hGIPR), and through structure activity analysis,
      we obtained compounds with low nanomolar affinities toward the hGluR, which were
      selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP
      1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the
      hGIPR and a >1000 fold selectivity over the hGLP-1R. A potent and selective
      glucagon receptor antagonist was demonstrated to inhibit glucagon-induced
      glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced
      hyperglycemia in Sprague-Dawley rats. Furthermore, the compound was shown to
      lower blood glucose in the ob/ob mouse after oral dosing.

PMID- 18707091
TI  - Effect of cathepsin K inhibitors on bone resorption.
AB  - On the basis of the pyrrolopyrimidine core structure that was previously
      discovered, cathepsin K inhibitors having a spiro amine at the P3 have been
      explored to enhance the target, bone marrow, tissue distribution. Several spiro
      structures were identified with improved distribution toward bone marrow. The
      representative inhibitor 7 of this series revealed in vivo reduction in C
      terminal telopeptide of type I collagen in rats and monkeys.

PMID- 18707092
TI  - Binding interaction analysis of the active site and its inhibitors for
      neuraminidase (N1 subtype) of human influenza virus by the integration of
      molecular docking, FMO calculation and 3D-QSAR CoMFA modeling.
AB  - Recently, the worldwide spread of A/H5N1 avian influenza with high virulence has
      highlighted the potential threat of human influenza pandemic. Tamiflu and Relenza
      are currently the only two anti-influenza drugs targeting the neuraminidase (NA)
      enzyme of human influenza virus. Reports of the emergence of drug resistance
      further make the development of new potent anti-influenza inhibitors a priority.
      The X-ray crystallographic study of A/H5N1 avian influenza NA subtypes (Russell,
      R. J. Nature 2006, 443, 45-49) has demonstrated that there exist two genetically
      distinct groups, group-1 (N1, N4, N5 and N8) and group-2 (N2, N3, N6, N7 and N9),
      whose conformations are substantially different. The detailed comparison of their
      active sites has established, heretofore, the most accurate and solid molecular
      basis of structure and mechanism for the development of new anti-influenza drugs.
      In the present study, a three-dimensional structure of N1 subtype of human
      influenza type A virus (N1hA) has been generated by homology modeling using the X
      ray crystallographic structure of N1 subtype of avian influenza virus (N1aA) as
      the template. Binding interaction analysis between the active site and its
      inhibitors has been performed by combining ab initio fragment molecular orbital
      (FMO) calculations and three-dimensional quantitative structure-activity
      relationship with comparative molecular field analysis (3D-QSAR CoMFA) modeling.
      Integrated with docking-based 3D-QSAR CoMFA modeling, molecular surface property
      (electrostatic and steric) mapping and FMO pair interaction analysis, a set of
      new receptor-ligand binding models and bioaffinity predictive models for rational
      design and virtual screening of more potent inhibitors of N1hA are established.
      In addition, the flexibility of the loop-150 of N1hA and N1aA has been examined
      by a series of molecular dynamics simulations.

PMID- 18707093
TI  - Aqueous Ln(III) luminescence agents derived from a tasty precursor.
AB  - The synthesis, characterization, and photophysical properties are reported for
      several Ln(III) complexes of a tetradentate chelate, 5LIO-MAM, derived from the
      common flavor enhancer "maltol". Eu(III), Yb(III), and Nd(III) form stable ML2
      complexes in aqueous solution that emit in the red or near-infrared (NIR) upon
      excitation at ca. 330 nm. The synthesis, aqueous stability, and photophysical
      properties are reported for a novel tetradentate ligand derived from maltol, a
      commonly used flavor enhancer. In aqueous solution, this chelate forms stable
      complexes with Ln(III) cations, and sensitized emission was observed from
      Eu(III), Yb(III), and Nd(III). A comparison with recently reported and
      structurally analogous ligands reveals a slightly higher basicity but lower
      complex stability with Eu(III) [pEu = 14.7(1)]. A very poor metal-centered
      quantum yield with Eu(III) was observed (Phi(tot) = 0.04%), which can be
      rationalized by the similar energy of the ligand triplet state and the Eu(III)
      (5)D0 emissive level. Instead, sensitized emission from the Yb(III) and Nd(III)
      cations was observed, which emit in the NIR.

PMID- 18707094
TI  - Topology analysis and nonlinear-optical-active properties of luminescent metal
      organic framework materials based on zinc/lead isophthalates.
AB  - Two 3D Zn(II) and Pb(II) isophthalates, [Zn(ip)]n (1) and [Pb4(mu4-O)(ip)3(H2O)]n
      (2) (H2ip = isophthalic acid), have been prepared under hydro(solvo)thermal
      conditions and characterized by single-crystal X-ray diffraction. The two
      complexes crystallize in different space groups (P4(3)2(1)2 for 1 and P2(1)/c for
      2) and have different bridging modes of the ip ligand. The 3D framework of 1 is
      constructed by the interconnection of ZnO4 polyhedra via ip ligands, which
      represents a chiral net with PtS-type topology. In contrast, complex 2 is formed
      by the combination of Pb4O-cluster secondary building units and has a novel
      (3.4.5)(3(2).4(5).5(6).6(7).7(2)) topology, which is the first ever example of a
      (3,7)-connected net. Complex 1 displays a second harmonic generation efficiency
      of about 1.5 times that of KH2PO4. Optical properties and thermal stabilities of
      the two complexes have been studied. Additionally, the calculations of band
      structure and density of states of 1 have also been performed with the density
      functional theory method.

PMID- 18707095
TI  - Transformation of proton-conducting Perovskite-type into fluorite-type fast oxide
      ion electrolytes using a CO2 capture technique and their electrical properties.
AB  - Fast oxide ion conducting Ce 1- x M x O 2-delta (M = In, Sm; x = 0.1, 0.2) and Ce
      0.8Sm 0.05Ca 0.15O 1.825 were prepared from the corresponding perovskite-like
      structured materials with nominal chemical composition of BaCe 1- x M x O 3-delta
      and BaCe 0.8Sm 0.05Ca 0.15O 2.825, respectively, by reacting with CO 2 at 800
      degrees C for 12 h. Powder X-ray diffraction (PXRD) analysis showed the formation
      of fluorite-type CeO 2 and BaCO 3 just after reaction with CO 2. The amount of CO
      2 gained per ceramic gram was found to be consistent with the Ba content. The CO
      2 reacted samples were washed with dilute HCl and water, and the resultant solid
      product was characterized structurally and electrically employing various solid
      state characterization methods, including PXRD, and alternating current (ac)
      impedance spectroscopy. The lattice constant of presently prepared Ce 1- x M x O
      2-delta and Ce 0.8Sm 0.05Ca 0. 15O 1.825 by a CO 2 capture technique follows the
      expected ionic radii trend. For example, In-doped Ce 0.9In 0.1O 1.95 (In (3+)
      (VIII) = 0.92 A) sample showed a fluorite-type cell constant of 5.398(1) A, which
      is lower than the parent CeO 2 (5.411 A, Ce (4+) (VIII) = 0.97 A). Our attempt to
      prepare single-phase In-doped CeO 2 samples at 800, 1000, and 1500 degrees C
      using the ceramic method was unsuccessful. However, we were able to prepare
      single-phase Ce 0.9In 0.1O 1.95 and Ce 0.8In 0.2O 1.9 by the CO 2 capture method
      from the corresponding barium perovskites. The PXRD studies showed that the In
      doped samples are thermodynamically unstable above 800 degrees C. The ac
      electrical conductivity studies using Pt electrodes showed the presence of bulk,
      grain-boundary, and electrode contributions over the investigated temperature
      range in the frequency range of 10 (-2)-10 (7) Hz. The bulk ionic conductivity
      and activation energy for the electrical conductivity of presently prepared Sm-
      and (Sm + Ca)-doped CeO 2 samples shows conductivities similar to those of
      materials prepared by the ceramic method reported in the literature. For
      instance, the conductivity of Ce 0.8Sm 0.2O 1.9 using the CO 2 capture technique
      was determined to be 4.1 x 10 (-3) S/cm, and the conductivity of the same sample
      prepared using the ceramic method was 3.9 x 10 (-3) S/cm at 500 degrees C. The
      apparent activation energy of the area-specific polarization resistance for the
      symmetric cell (Sm,Sr)CoO 3- x |Ce 0.8Sm 0.2O 1.9|(Sm,Sr)CoO 3- x was determined
      to be 1 eV in air.

PMID- 18707096
TI  - Synthesis, structures, and solution dynamics of palladium complexes of quinoline
      functionalized N-heterocyclic carbenes.
AB  - A new type of quinoline-functionalized palladium N-heterocyclic carbene (NHC)
      complexes has been synthesized via silver transmetallation. The quinoline moiety
      was either directly attached to the imidazole ring or linked to it by a methylene
      group. NHCs with a methylene linker tend to form trans biscarbene complexes in
      the reaction of Pd(COD)Cl2, while NHCs without any linker form chelating NHC
      quinoline (NHC-N) complexes. These two types of carbenes also react with
      [Pd(allyl)Cl]2 to give monodentate NHC palladium eta(3)-allyl chlorides
      [Pd(NHC)(allyl)Cl]. Fluxionality in the NMR time scale was observed for most
      complexes, and the origin of their dynamic behaviors was discussed for each type
      of structure. For [Pd(NHC)(allyl)Cl] with a relatively small wing tip group of
      the NHC, the fluxionality (selective line-broadening of (1)H NMR signals) is
      caused by selective eta(3)-eta(1)-eta(3) allyl isomerization. For NHC with a
      bulkier (t)Bu group, a different line-broadening pattern was observed and was
      ascribed to partially hindered Pd-C(carbene) bond rotation. For cationic
      chelating complexes [Pd(NHC-N)(allyl)]BF4, the dynamic exchange process likely
      originates from a dissociative boat-to-boat inversion of 7-membered
      palladacycles. Activation parameters were measured for this process. Crystal
      structures were reported for representative complexes in each category.

PMID- 18707097
TI  - Synthesis, structure, and magnetism of three azido-bridged Co2+ compounds with a
      flexible coligand 1,2-(tetrazole-1-yl)ethane.
AB  - By utilizing suitable coligand endi (1,2-(tetrazole-1-yl)ethane)) with variable
      conformations, we synthesized three new azido-bridged Co(2+) compounds with
      molecular formulas Co(endi)(N3)2 (1, 3) and Co(endi)2(N3)2 (2) by tuning the
      stoichiometric ratio of ligand/metal and the concentration of the solution. All
      of the compounds have been characterized structurally and magnetically. In all
      three structures, the azide ions use the end-to-end mode to link the Co(2+)
      centers to the 1D chain (1) and 2D (4,4) layers (2 and 3). The endi coligands
      adopt a trans conformation in compound 1 and a gauche conformation in compounds 2
      and 3. Linked by bridging endi, the 1D chains in compound 1 and 2D layers in
      compound 3 are extended, resulting in the final 2D layer for compound 1 and the
      3D network for compound 3, whereas in compound 2, the endi acts as only a
      terminal ligand to separate the 2D layers. Compound 1 consists of dual end-to-end
      azido-bridged 1D Co(2+) chains that are linked by trans endi into a 2D layer and
      are further extended to a 3D framework through H bonds. Compound 2 is a 2D (4,4)
      layer that is connected by end-to-end azido ions. The gauche endi ligands act as
      terminal ligands to separate the neighboring layers thoroughly. Compound 3 has a
      (4,4) 2D layer that is similar to that of compound 2, and these layers are
      further extended to a 3D network through gauche endi. The magnetic investigation
      shows that compound 3 is antiferromagnetically coupled and compound 2 is a weak
      ferromagnet with a critical temperature of 22 K, which is quite high compared
      with that of the previously reported 2D azido-bridged Co(2+) compounds.

PMID- 18707098
TI  - Structural and magnetic characterization of a mu-1,5-dicyanamide-bridged iron
      basic carboxylate [Fe3O(O2C(CH3)3)6] 1D chain.
AB  - We are reporting an unprecedented example of a mu-1,5-dicyanamide (dca)-bridged
      iron basic carboxylate, [Fe3O(O2C(CH3)3)6], 1D chain. As revealed from X-ray
      determination, the Fe3O cores are arranged in a zigzag configuration along the
      chain and strictly aligned in the same plane. The chains are well-isolated by the
      bulky tert-butyl groups. Magnetic measurements showed that the Fe3O units are
      weakly antiferromagnetically coupled (J = -0.6 cm(-1)) through the dca ligand
      while possessing a well-isolated S = 1/2 spin ground state arising from competing
      antiferromagnetic interactions.

PMID- 18707099
TI  - Transition-metal nanocluster size vs formation time and the catalytically
      effective nucleus number: a mechanism-based treatment.
AB  - A mechanism-based equation for the size of a forming transition-metal nanocluster
      vs time has been derived based on the Finke-Watzky two-step mechanism for
      transition-metal nanocluster nucleation (A --> B, rate constant k1) and
      autocatalytic growth (A + B --> 2B, rate constant k2), where A is the nanocluster
      precursor and B is the growing nanocluster. The resultant equation expresses
      nanocluster diameter as a function of time, D(t), in terms of k1, k2, the initial
      concentration of the nanocluster precursor complex, [A]0, and the number of
      catalytically effective nuclei derived from either (i) the final nanocluster
      size, D(f), or (ii) the number of atoms in the average catalytically effective
      nucleus, N*, and the induction period time, t ind (N* being by definition the
      number of atoms present in the average size nucleus at the end of the induction
      period and when observable catalysis begins). By fitting experimentally
      determined nanocluster size vs time data using this equation, evidence for the
      validity of the equation is obtained for Ir(0) nanoclusters formed from the well
      studied system of H2 reduction of the precursor [(1,5-COD)Ir x P2W15Nb3O62](8-).
      The D(t) equation is then used to determine N* for nine prior Ir(0) nanocluster
      preparations from five different [(1,5-COD)Ir(+)]n [anion(n-)] precursors. Also
      given is a relationship allowing one to interconvert between nanocluster size
      data and nanocluster precursor concentration data, again when the two-step
      nucleation and growth mechanism has been shown to apply. Some of the key
      experimental factors that are known to affect the kinetics of nanocluster
      formation, and therefore nanocluster size, are also summarized. A look ahead to
      needed future work is also provided.

PMID- 18707100
TI  - Controlled assembly of eccentrically encapsulated gold nanoparticles.
AB  - Controlled partial attachment of polymer on gold nanoparticles breaks the
      symmetry of their surface functionalities, allowing tailored assembly of the
      nanoparticles.

PMID- 18707101
TI  - Low-temperature solution synthesis of the non-equilibrium ordered intermetallic
      compounds Au3Fe, Au3Co, and Au3Ni as nanocrystals.
AB  - Alloys and intermetallic compounds of Au with the 3d transition metals Fe, Co,
      and Ni are nonequilibrium phases that have many useful potential applications as
      catalytic, magnetic, optic, and multifunctional magneto-optic materials. However,
      the atomically ordered Au-M (M = Fe, Co, Ni) intermetallics are particularly
      elusive from a synthetic standpoint. Here we report the low-temperature solution
      synthesis of the L12 (Cu3Au-type) intermetallic compounds Au3Fe, Au3Co, and Au3Ni
      using n-butyllithium as a reducing agent. Reaction pathway studies for the Au3Co
      system indicate that Au nucleates first, followed by Co incorporation to form the
      intermetallic. The nonequilibrium intermetallic nanocrystals have been
      characterized by powder XRD, TEM, EDS, selected area electron diffraction, and
      nanobeam electron diffraction, which collectively confirm the compositions and
      superlattice structures.

PMID- 18707102
TI  - Low-temperature single-wall carbon nanotubes synthesis: feedstock decomposition
      limited growth.
AB  - We report on the lowest temperature of SWCNT growth using endothermic
      decomposition of CH4 gas on a specially activated alumina-supported Fe:Mo
      catalyst. However, the observed lowest growth temperature (560 degrees C) is
      higher than that reported previously for exothermic feedstock type. Our
      observation indicates that the decomposition threshold temperature of the
      feedstock limits the SWCNT growth. This study also suggests that, by using more
      active carbon feedstock or somehow facilitating its decomposition, one could
      enable the synthesis of SWCNT at an even lower temperature.

PMID- 18707103
TI  - Activation of CS2 and CS by ML3 complexes.
AB  - The aim of this study was to determine the best neutral ML3 metal complexes for
      activating and cleaving the multiple bonds in CS2 and CS. Current experimental
      results show that, so far, only one bond in CS2 can be cleaved, and that CS can
      be activated but the bond is not broken. In the work described in this paper,
      density functional theory calculations have been used to evaluate the
      effectiveness of different ML3 complexes to activate the C-S bonds in CS2 and CS,
      with M = Mo, Re, W, and Ta and L = NH2. These calculations show that the
      combination of Re and Ta in the L3Re/CS2/TaL3 complex would be the most promising
      system for the cleavage of both C-S bonds of CS2. The reaction to cleave both C-S
      bonds is predicted to be exothermic by about 700 kJ mol(-1) and to proceed in an
      almost barrierless fashion. In addition, we are able to rationalize why the
      breaking of the C-S bond in CS has not been observed experimentally with M = Mo:
      this reaction is strongly endothermic. There is a subtle interplay between charge
      transfer and pi back-donation, and it appears that the Mo-C and Mo-S bonds are
      not strong enough to compensate for the breaking of the C-S bond. Our results
      suggest that, instead, CS could be cleaved with ReL3 or, even better, with a
      combination of ReL3 and TaL3. Molecular orbitals and Mulliken charges have been
      used to help explain these trends and to make predictions about the most
      promising systems for future experimental exploration.

PMID- 18707104
TI  - Amino acid selective cross-saturation method for identification of proximal
      residue pairs in a protein-protein complex.
AB  - We describe an NMR-based approach, the amino acid selective cross-saturation
      (ASCS) method, to identify the pairs of the interface residues of protein-protein
      complexes. ASCS uses a "cross-saturation (CS)-donor" protein, in which only one
      amino acid is selectively (1)H-labeled in a (2)H-background, and a "CS-acceptor"
      protein with uniform (2)H, (15)N labeling. Irradiation of the (1)H-labeled amino
      acid, which exists only in the donor, decreases the intensity of the (1)H- (15)N
      HSQC signals of the acceptor residues proximal to the (1)H-labeled CS-source
      residue(s) through the CS phenomenon. Given the three-dimensional structure of
      each protein in the complex, but not the complex structure, the combinatorial
      analysis of multiple ASCS results specify the CS-source residue(s), based on the
      spatial complementarity between the CS-source residues on the CS donor and the
      cross-saturated amide protons on the acceptor. NMR investigations of the labeling
      selectivity and efficiency in an E. coli host, which are critical for ASCS,
      revealed that Ala, Arg, His, Ile, Leu, Lys, Met, Phe, Pro, Trp, and Tyr are
      selectively labeled with a high (1)H/(2)H ratio. The observation of the ASCS was
      then confirmed using the known structure of the yeast ubiquitin (Ub) and yeast
      ubiquitin hydrolase 1 (YUH1). Conversely, reasonable candidates for the CS-source
      residues were suggested by the analysis of the ASCS results, with reference to
      the individual structures of YUH1 and Ub. The pairwise distance information
      between the CS-source residues and the cross-saturated amide groups obtained by
      ASCS will be useful for modeling protein-protein complexes.

PMID- 18707105
TI  - Ring expansion of lactones and lactams via propiolate 1-carbon intercalation.
AB  - Readily available five- and six-membered lactones and N-sulfonyllactams undergo
      efficient addition of t-butyl propiolate, and the resulting adducts undergo
      cycloisomerization to six- and seven-membered cyclic ethers or amines in the
      presence of pyridinium acetate. The ring expansion process occurs in generally
      good yields and is proposed to involve a nucleophilic catalysis mechanism.

PMID- 18707106
TI  - Synthesis and activity of largazole analogues with linker and macrocycle
      modification.
AB  - To characterize largazole's structural requirements for histone deacetylase
      (HDAC) inhibitory and antiproliferative activities, a series of analogues with
      modifications to the side chain or 16-membered macrocycle were prepared and
      biologically evaluated. Structure-activity relationships suggested that the four
      atom linker between the macrocycle and octanoyl group in the side chain and the
      (S)-configuration at the C17 position are critical to repression of HDAC
      activity. However, the valine residue in the macrocycle can be replaced with
      alanine without significant loss of activity.

PMID- 18707107
TI  - Stereochemistry of the singlet oxygenation of simple alkenes: a stereospecific
      transformation.
AB  - The stereochemistry of the allylic oxidation (ene reaction) mediated by singlet
      oxygen ((1)O2), using the optically active alkene (S,S)-cis-1,4-diphenyl-2-butene
      1,4-d2 , in MeOH and aprotic solvents was investigated. Our findings indicate
      that the title reaction is a highly stereospecific suprafacial process,
      independent of solvent polarity. The observation of an isotope effect, which
      matches the stereogenic ratio exactly, rules out biradical or open dipolar
      intermediates.

PMID- 18707108
TI  - Preparation of highly photosensitizing liposomes with fullerene-doped lipid
      bilayer using dispersion-controllable molecular exchange reactions.
AB  - Fullerene-containing liposomes with high photosensitization ability were
      prepared. Disaggregated fullerenes were efficiently injected into the bilayer of
      liposomes by a phototriggered molecular exchange reaction. These liposomes showed
      far higher photoreactivity than liposomes thermally produced by heating and
      microwave irradiation. This result indicates that control of self-aggregation of
      fullerene leads to a high quantum yield for the photoreaction because of the
      suppression of self-quenching of photoexcited fullerenes.

PMID- 18707109
TI  - The coupling of isonitriles and carboxylic acids occurring by sequential
      concerted rearrangement mechanisms.
AB  - Mechanisms for the recently described reactions of isonitriles with carboxylic
      acids (Li, X.; Danishefsky, S. J. J. Am. Chem. Soc. 2008, 130, 5446) are explored
      with the B3LYP density functional method. The mechanism involves the formation of
      a carboxylate mixed formimidic anhydride intermediate via a concerted mechanism.
      This intermediate is then transformed to an N-formylamide by a concerted
      pseudopericyclic [1,3]-acyl shift. Mechanisms involving zwitterions or diradicals
      are discounted.

PMID- 18707110
TI  - Preparation of ferulic acid from agricultural wastes: its improved extraction and
      purification.
AB  - Ferulic acid (FA) is a phenolic antioxidant present in plants, which is widely
      used in the food and cosmetic industry. In the present study, various
      agricultural wastes such as maize bran, rice bran, wheat bran, wheat straw, sugar
      cane baggasse, pineapple peels, orange peels, and pomegranate peels were screened
      for the presence of esterified FA (EFA). Among the sources screened, maize bran
      was found to contain the highest amount of EFA. Pineapple peels, orange peels,
      and pomegranate peels were also found to contain traces of EFA. Alkaline
      extraction of EFA from maize bran was carried out using 2 M NaOH. Response
      surface methodology (RSM) was used for optimization of EFA extraction, which
      resulted in a 1.3-fold increase as compared to the unoptimized conventional
      extraction technique. FA was analyzed by means of high-performance liquid
      chromatography (HPLC). Purification was carried out by adsorption chromatography
      using Amberlite XAD-16 followed by preparative high-performance thin-layer
      chromatography (HPTLC). The recovery of Amberlite XAD-16 purified FA was up to
      57.97% with HPLC purity 50.89%. The fold purity achieved was 1.35. After
      preparative HPTLC, the maximum HPLC purity obtained was 95.35% along with an
      increase in fold purity up to 2.53.

PMID- 18707111
TI  - Stability and emulsifying capacity of biosurfactants obtained from
      lignocellulosic sources using Lactobacillus pentosus.
AB  - Lactobacillus pentosus grown on sugars from agricultural residues produces
      biosurfactants with emulsifying properties that could facilitate the
      bioremediation of hydrocarbon contaminated sites. The biosurfactans obtained
      after growing L. pentosus cells on distilled grape marc hydrolyzates gave values
      of relative emulsion volume (EV) close to 50%, being stable after 72 h when
      gasoline or kerosene were employed. These EV values were higher than those
      achieved using commercial surfactin (14.1% for gasoline and 27.2% for kerosene).
      Moreover, assays carried out with kerosene showed that L. pentosus produced
      biosurfactants from distilled grape marc hydrolyzates with the highest
      stabilizing capacity value (ES) to maintain the emulsion (99%) followed by
      biosurfactants produced from hazelnut shell hydrolyzates (97%). These data are
      comparable with those obtained using sodium dodecyl sulfate, SDS (87.7%), whereas
      surfactin only gave an ES value of 65.4%. Consequently, this work shows that
      utilization of low-cost feedstock agricultural residues as substrates for
      producing biosurfactants/bioemulsifiers is possible thus removing obstacles for
      the wide-scale industrial application of biosurfactants/bioemulsifiers.

PMID- 18707112
TI  - Model studies on the degradation of phenylalanine initiated by lipid
      hydroperoxides and their secondary and tertiary oxidation products.
AB  - The reaction of methyl 13-hydroperoxyoctadeca-9,11-dienoate (MeLOOH), methyl 13
      hydroperoxyoctadeca-9,11,15-trienoate (MeLnOOH), methyl 13-hydroxyoctadeca-9,11
      dienoate (MeLOH), methyl 13-oxooctadeca-9,11-dienoate (MeLCO), methyl 9,10-epoxy
      13-hydroxy-11-octadecenoate (MeLEPOH), and methyl 9,10-epoxy-13-oxo-11
      octadecenoate (MeLEPCO) with phenylalanine was studied to determine the
      comparative reactivity of primary, secondary, and tertiary lipid oxidation
      products in the Strecker degradation of amino acids. All assayed lipids were able
      to degrade the amino acid to a high extent, although the lipid reactivity
      decreased slightly in the following order: MeLEPCO > or = MeLCO > MeLEPOH > or =
      MeLOH > MeLOOH approximately = MeLnOOH. These data confirmed the ability of many
      lipid oxidation products to degrade amino acids by a Strecker-type mechanism and
      suggested that, once the lipid oxidation is produced, a significant Strecker
      degradation of surrounding amino acids should be expected. The contribution of
      different competitive mechanisms to this degradation is proposed, among which the
      conversion of the different lipid oxidation products assayed into the most
      reactive MeLEPCO and the fractionation of long-chain primary and secondary lipid
      oxidation products into short-chain aldehydes are likely to play a major role.

PMID- 18707113
TI  - Effects of hydroxytyrosol and hydroxytyrosol acetate administration to rats on
      platelet function compared to acetylsalicylic acid.
AB  - Virgin olive oil (VOO) contains the polyphenols hydroxytyrosol (HT) and
      hydroxytyrosol acetate (HT-AC). This study investigated the antiplatelet effect
      of HT and HT-AC in healthy rats and compared their effects to acetylsalicylic
      acid (ASA). All compounds were administered orally for 7 days. HT and HT-AC
      inhibited platelet aggregation in whole blood, with a 50% inhibitory dose (ID50)
      of 48.25 mg/kg per day for HT, 16.05 mg/kg per day for HT-AC, and 2.42 mg/kg per
      day for ASA. Platelet synthesis of thromboxane B2 was inhibited by up to 30% by
      HT and 37% by HT-AC; the ID50 of this effect for ASA was 1.09 mg/kg per day.
      Vascular prostacyclin production was inhibited by up to 27.5% by HT and 32% by HT
      AC; the ID50 of this effect for ASA was 6.75 mg/kg per day. Vascular nitric oxide
      production was increased by up to 34.2% by HT, 66% by HT-AC, and 64% by ASA. We
      conclude that HT and HT-AC administered orally inhibited platelet aggregation in
      rats and that a decrease in thromboxane synthesis along with an increase in
      nitric oxide production contributed to this effect.

PMID- 18707114
TI  - Massive accumulation of gallic acid and unique occurrence of myricetin,
      quercetin, and kaempferol in preparing old oolong tea.
AB  - Old oolong tea, tasting superior and empirically considered beneficial for human
      health, is prepared by long-term storage accompanied with periodic drying for
      refinement. Analyzing infusions of three old and one newly prepared oolong teas
      showed that significant lower (-)-epigallocatechin gallate (EGCG) but higher
      gallic acid contents were detected in the old teas compared to the new one. The
      possibility of releasing gallic acid from EGCG in old tea preparation was
      supported by an in vitro observation of gallic acid degraded from EGCG under
      heating conditions mimicking the drying process. Moreover, three minor flavonols,
      myricetin, quercetin, and kaempferol, that were undetectable in the new tea
      occurred in all of the three old teas. Converting the new oolong tea into an old
      one by periodic drying revealed the same characteristic observation, i.e.,
      massive accumulation of gallic acid presumably released from EGCG and unique
      occurrence of flavonols putatively decomposed from flavonol glycosides.

PMID- 18707115
TI  - Analysis of oil composition in cultivars and wild species of oat (Avena sp.).
AB  - Oil quality and content were analyzed in 33 accessions from 13 wild species and
      10 accessions of cultivated oat. Wild oat species tended to have higher oil and
      18:1 fatty acid (FA) contents and lower amounts of 18:2 and 18:3 FAs as compared
      to cultivated oats. In addition to common FAs, minor amounts of several hydroxy
      and epoxy FAs were also present in the oat oil and mainly confined to specific
      lipid classes. These unusual FAs included the previously reported 15-hydroxy 18:2
      (Delta9,12) (avenoleic acid) mostly found among polar lipids and a novel 7
      hydroxyhexadecanoic acid located to 1,2-diacylglycerol. The present study
      highlights the potential of making use of the existing germplasm, consisting of
      wild oat species, in breeding programs for achieving new oat varieties that
      produce a range of oils with different FA compositions as well as having high oil
      contents. However, in one matter, oats apparently lack genetic diversity and that
      is for oil qualities that are highly enriched in the omega 3 (omega-3) FA 18:3.
      Consequently, developing oat cultivars with highly unsaturated oils will need
      involvement of other techniques such as biotechnology.

PMID- 18707116
TI  - Novel biological properties of Oenothera paradoxa defatted seed extracts: effects
      on metallopeptidase activity.
AB  - In this study, for the first time, we used the in vitro metallopeptidase model
      for the identification of a potential novel activity of defatted evening primrose
      seed extracts. Prepared extracts of different polarity (aqueous, 60% ethanolic,
      isopropanolic, and 30% isopropanolic) at concentrations of 1.5-100 microg/mL
      exhibited a significant and dose dependent inhibition of three tested enzymes.
      The 50% inhibition of enzymes activity showed that aminopeptidase N (APN) was the
      enzyme affected to the greatest extent with IC50 at the level of 2.8 microg/mL
      and 2.9 microg/mL for aqueous and 30% isopropanolic extracts, respectively. The
      activity of neutral endopeptidase (NEP) was quite strongly inhibited by the
      extracts as well. The HPLC-DAD analysis and bioguided fractionation led to the
      identification of four active compounds: (-)-epicatechin gallate,
      proanthocyanidin B3, oenothein B, and penta-O-galloyl-beta-D-glucose (PGG).
      Oenothein B has been shown previously to inhibit metallopeptidases. The three
      other compounds are known to inhibit angiotensin-converting enzyme (ACE), but
      they have not been previously reported to inhibit the NEP and APN activity. PGG
      and procyanidins with different degrees of polymerization, as the dominating
      compounds in O. paradoxa seeds, seemed to play a role in the crude extract
      activity.

PMID- 18707117
TI  - Consumption of a functional fermented milk containing collagen hydrolysate
      improves the concentration of collagen-specific amino acids in plasma.
AB  - Clinical studies have shown that collagen hydrolysate (CH) may be able to protect
      joints from damage, strengthen joints, and reduce pain from conditions like
      osteoarthritis. CH is a collection of amino acids and bioactive peptides, which
      allows for easy absorption into the blood stream and distribution in tissues.
      However, although various matrices have been studied, the absorption of specific
      amino acids from CH added to a fresh fermented milk product (FMP) was not
      studied. The primary objective of the present study was to compare the plasma
      concentrations of four representative amino acids from the CH (glycine, proline,
      hydroxyproline, and hydroxylysine) contained in a single administration of a FMP
      with that of a single administration of an equal amount of neat hydrolyzed
      collagen. These four amino acids were chosen because they have already been used
      as markers of CH absorption rate and bioavailability. This was a single-center,
      randomized open, and crossover study with two periods, which was performed in 15
      healthy male subjects. The subjects received randomly and in fasted state a
      single dose of product 1 (10 g of CH in 100 mL of FMP) and product 2 (10 g of CH
      dissolved in 100 mL of water) separated by at least 5 days. After administration,
      the subjects were assessed for plasma concentrations of amino acids and for urine
      concentrations of hydroxyproline. After FMP administration, mean values of the
      maximal concentration (Cmax) of the four amino acids were greater than after
      ingredient administration (p < 0.05). This effect was related to an increased
      Cmax of proline (p < 0.05). In conclusion, because of their physicochemical
      characteristics, the fermentation process, and the great homogeneity of the
      preparation, this milk product improves the plasma concentration of amino acids
      from CH, that is, proline. The present study suggests an interesting role for FMP
      containing CH to improve the plasmatic availability of collagen-specific amino
      acids. Hence, this FMP product could be of potential interest in the management
      of joint diseases.

PMID- 18707118
TI  - Physiological responses to novel carbohydrates as assessed using canine and avian
      models.
AB  - The objective was to quantify in vitro digestion, true metabolizable energy
      (TME(n)) content, glycemic and insulinemic responses, and gastrointestinal
      tolerance to fructose (Fruc), maltodextrin (Malt), polydextrose (Poly), pullulan
      (Pull), resistant starch (RS), sorbitol (Sorb), and xanthan gum (Xan). Limited
      digestion of RS, Poly, and Xan occurred. Fruc, Malt, and Sorb resulted in the
      highest (P < 0.05) TME(n) values, Pull was intermediate, and RS and Poly were
      lowest. Malt had the highest (P < 0.05) area under the curve for glucose and
      insulin in the glycemic tests. Gastrointestinal tolerance was examined for diets
      containing carbohydrates at either 100 or 200% of the adequate intake (AI) value
      for dietary fiber. At 100% and 200% AI, Malt, RS, and Sorb resulted in ideal
      fecal scores, while Pull and Xan resulted in looser stools and Poly resulted in
      diarrhea. The carbohydrates studied varied widely in physiological outcomes.
      Certain carbohydrates could potentially benefit large bowel health.

PMID- 18707119
TI  - Measurement of condensed tannins and dry matter in red grape homogenates using
      near infrared spectroscopy and partial least squares.
AB  - Samples (n = 620) of homogenized red grape berries were analyzed using a visible
      and near-infrared (NIR) spectrophotometer (400-2500 nm) in reflectance. The
      spectra and the analytical data were used to develop partial least-squares
      calibrations to predict dry matter (DM) content and condensed tannins (CT)
      concentrations. The coefficient of determination in cross-validation and the
      standard error of cross-validation were 0.92 and 0.83% w/w for DM and 0.86 and
      0.46 mg/g epicatechin equivalents for CT, respectively. The standard error in
      prediction was 1.34% w/w for DM and 0.89 mg/g epicatechin equivalents for CT,
      respectively. By implementing a NIR spectroscopy method to measure DM and CT in
      red grape homogenates, we have developed an approach that is suited to large
      scale compositional analysis in commercial wine production facilities, as it
      enables the analysis of large numbers of samples needed to stream batches of
      fruit. From an economical point of view, the calibration models could be achieved
      with relatively small data sets. Thus, NIR offers a suitable and efficient tool
      for the simultaneous measurement of DM and CT in addition to other important
      parameters in red grape homogenates such as total anthocyanins, total soluble
      solids, and pH, with minimal sample preparation and low cost.

PMID- 18707120
TI  - Preparation and characterization of the inclusion complex of chlorpyrifos in
      cyclodextrins to improve insecticide formulations.
AB  - The chemical control of crops by organophosphate insecticide treatment is usually
      limited because the insecticides do not maintain their efficiency for long
      periods for several reasons, including environmental conditions or rapid
      degradation of the active ingredient. Chlorpyrifos is an organophosphate
      insecticide used worldwide to control a variety of soil insects and arthropods in
      a wide range of crops. It is easily soluble in organic solvents but shows poor
      water solubility. The inclusion of chrorpyrifos in cyclodextrins (CDs) improves
      its water solubility, bioavailability, and insecticidal activity and helps
      prevent overdosing, leading to more cost-effective and more environmentally
      friendly agricultural practices. Solubility studies of chlorpyrifos in the
      presence of different types of CDs show G2-beta-CDs to be the most effective CDs
      in the complexation process, giving 1:2 complexes, with complexation constant
      (Kc) values of 12.34 +/- 3.1 M(-1) for K1 and 3895 +/- 183 M(-1) for K2. These
      complexation constant values were corroborated by applying a fluorimetric method.

PMID- 18707121
TI  - 1H nuclear magnetic resonance-based metabolomic characterization of wines by
      grape varieties and production areas.
AB  - (1)H NMR spectroscopy was used to investigate the metabolic differences in wines
      produced from different grape varieties and different regions. A significant
      separation among wines from Campbell Early, Cabernet Sauvignon, and Shiraz grapes
      was observed using principal component analysis (PCA) and partial least squares
      discriminant analysis (PLS-DA). The metabolites contributing to the separation
      were assigned to be 2,3-butanediol, lactate, acetate, proline, succinate, malate,
      glycerol, tartarate, glucose, and phenolic compounds by PCA and PLS-DA loading
      plots. Wines produced from Cabernet Sauvignon grapes harvested in the continental
      areas of Australia, France, and California were also separated. PLS-DA loading
      plots revealed that the level of proline in Californian Cabernet Sauvignon wines
      was higher than that in Australian and French Cabernet Sauvignon, Australian
      Shiraz, and Korean Campbell Early wines, showing that the chemical composition of
      the grape berries varies with the variety and growing area. This study highlights
      the applicability of NMR-based metabolomics with multivariate statistical data
      sets in determining wine quality and product origin.

PMID- 18707122
TI  - Use of a commercial protease and yeasts to obtain CGRP-like molecules from saithe
      protein.
AB  - Different bioactive molecules, such as CGRP-like peptides, can be found in fish
      protein hydrolysates. Calcitonin gene-related peptide (CGRP) is a neuropeptide
      known to act as a potent arterial and venous vasodilator in humans. This study
      focuses on the industrial obtaining of CGRP-like molecules from saithe
      (Pollachius virens) byproduct, derived from the filleting process. Protein from
      P. virens was primarily hydrolyzed with Alcalase and later treated with
      Saccharomyces cerevisiae live cells. Treatment with Saccharomyces doubled the
      quantity of bioactive molecules obtained. The CGRP-like molecules were partially
      purified by chromatography, and the immunoreactive material was further analyzed
      for its CGRP-like bioactivity, using a specific radioreceptor assay. The
      concentration of CGRP-like molecules increased over 100-fold after purification.
      The bioactive molecules were able to induce cyclic AMP stimulation in rat liver
      membranes. Finally, partial sequencing of the bioactive peptide was performed,
      showing some homology with alpha-actin and myosin of several fish species.

PMID- 18707123
TI  - trans-Free margarines prepared with canola oil/palm stearin/palm kernel oil-based
      structured lipids.
AB  - Structured lipids (SLs) for formulating trans-free margarines were synthesized by
      lipase-catalyzed interesterification of the blends of canola oil (CO), palm
      stearin (PS), and palm kernel oil (PKO) in weight ratios (CO/PS/PKO) of 40:60:0,
      40:50:10, 40:40:20, 40:30:30, 50:30:20, and 60:25:15. The atherogenicity was
      determined using fatty acid profiles. We also determined the physical properties
      (melting/crystallization profiles, solid fat content, polymorphism, and
      microstructure) of SLs and the textural properties of margarines made with the
      SLs. The SLs from the 50:30:20 and 60:25:15 blends had atherogenic indices
      similar to or lower than those of the commercial trans (CTMF) and similar to the
      trans-free margarine fats (CTFMF). SLs from the blends with PKO contained a wide
      range of fatty acids (C6-C20) and had more beta' than beta polymorphs. Margarines
      made with SLs from 50:30:20 and 60:25:15 blends possessed similar hardness,
      adhesiveness, or cohesiveness to margarines made with CTMF and CTFMF,
      respectively. Therefore, CO/PS/PKO-based SLs were suitable for formulating trans
      free margarines with low atherogenicity and desirable textural properties.

PMID- 18707125
TI  - Structural characterization and reversal of the natural organophosphate
      resistance of a D-type esterase, Saccharomyces cerevisiae S-formylglutathione
      hydrolase.
AB  - Saccharomyces cerevisiae expresses a 67.8 kDa homodimeric serine thioesterase, S
      formylglutathione hydrolase (SFGH), that is 39.9% identical with human esterase
      D. Both enzymes possess significant carboxylesterase and S-formylglutathione
      thioesterase activity but are unusually resistant to organophosphate (OP)
      inhibitors. We determined the X-ray crystal structure of yeast (y) SFGH to 2.3 A
      resolution by multiwavelength anomalous dispersion and used the structure to
      guide site-specific mutagenesis experiments addressing substrate and inhibitor
      reactivity. Our results demonstrate a steric mechanism of OP resistance mediated
      by a single indole ring (W197) located in an enzyme "acyl pocket". The W197I
      substitution enhances ySFGH reactivity with paraoxon by >1000-fold ( k i (W197I)
      = 16 +/- 2 mM (-1) h (-1)), thereby overcoming natural OP resistance. W197I
      increases the rate of OP inhibition under pseudo-first-order conditions but does
      not accelerate OP hydrolysis. The structure of the paraoxon-inhibited W197I
      variant was determined by molecular replacement (2.2 A); it revealed a stabilized
      sulfenic acid at Cys60. Wild-type (WT) ySFGH is inhibited by thiol reactive
      compounds and is sensitive to oxidation; thus, the cysteine sulfenic acid may
      play a role in the regulation of a "D-type" esterase. The structure of the W197I
      variant is the first reported cysteine sulfenic acid in a serine esterase. We
      constructed five Cys60/W197I variants and show that introducing a positive charge
      near the oxyanion hole, W197I/C60R or W197I/C60K, results in a further
      enhancement of the rates of phosphorylation with paraoxon ( k i = 42 or 80 mM (
      1) h (-1), respectively) but does not affect the dephosphorylation of the enzyme.
      We also characterized three histidine substitutions near the oxyanion hole, G57H,
      L58H, and M162H, which significantly decrease esterase activity.

PMID- 18707126
TI  - Identification of key sequence determinants for the inhibitory function of the
      prodomain of TACE.
AB  - The TNFalpha converting enzyme (TACE) is a zinc metalloproteinase that mediates
      shedding of multiple cell surface proteins. Regulation of TACE enzymatic activity
      is ultimately mediated via proteolytic removal of its inhibitory prodomain.
      Sequence determinants for TACE prodomain inhibition of the catalytic domain are
      yet to be identified. Surprisingly, although TACE and ADAM 10 (closest homologue)
      share only 23% sequence identity at their prodomains, the latter in isolation
      inhibits TACE with the same potency as TACE own prodomain. In contrast, the
      prodomain of ADAM 9 inhibited TACE only weakly. Detailed analysis of ADAM
      prodomains revealed two short regions for which TACE and ADAM 10 depart
      dramatically from all other family members. We prepared TACE prodomain variants
      containing full or partial switches to ADAM 9 residues at those two regions and
      examined their functional properties. Variants containing ADAM 9 substitutions
      including amino acid residues 72-82 and 126-137 were fully inactive for TACE
      inhibition. A third variant comprising residues 114-125 was active but at lower
      potency relative to wild type. All inactive variants appeared to be correctly
      folded. Finally, the amino acid residue Phe72 and the motif Asp-Asp-Val-Ile137
      were identified within those regions as key determinants for TACE prodomain
      inhibitory function. We conclude that TACE and ADAM 10 prodomains are
      functionally equivalent in a way that separates them from the rest of the ADAM
      family.

PMID- 18707127
TI  - The low-pH unfolded state of the C-terminal domain of the ribosomal protein L9
      contains significant secondary structure in the absence of denaturant but is no
      more compact than the low-pH urea unfolded state.
AB  - There is considerable interest in the properties of the unfolded states of
      proteins, particularly unfolded states which can be populated in the absence of
      high concentrations of denaturants. Interest in the unfolded state ensemble
      reflects the fact that it is the starting point for protein folding as well as
      the reference state for protein stability studies and can be the starting state
      for pathological aggregation. The unfolded state of the C-terminal domain
      (residues 58-149) of the ribosomal protein L9 (CTL9) can be populated in the
      absence of denaturant at low pH. CTL9 is a 92-residue globular alpha, beta
      protein. The low-pH unfolded state contains more secondary structure than the low
      pH urea unfolded state, but it is not a molten globule. Backbone ( (1)H, (13)C,
      and (15)N) NMR assignments as well as side chain (13)C beta and (1)H beta
      assignments and (15)N R 2 values were obtained for the pH 2.0 unfolded form of
      CTL9 and for the urea unfolded state at pH 2.5. Analysis of the deviations of the
      chemical shifts from random coil values indicates that residues that comprise the
      two helices in the native state show a clear preference for adopting helical phi
      and psi angles in the pH 2.0 unfolded state. There is a less pronounced but
      nevertheless clear tendency for residues 107-124 to preferentially populate
      helical phi and psi values in the unfolded state. The urea unfolded state has no
      detectable tendency to populate any type of secondary structure even though it is
      as compact as the pH 2.0 unfolded state. Comparison of the two unfolded forms of
      CTL9 provides direct experimental evidence that states which differ significantly
      in their secondary structure can have identical hydrodynamic properties. This in
      turn demonstrates that global parameters such as R h or R g are very poor
      indicators of "random coil" behavior.

PMID- 18707129
TI  - FAB mass spectrometry of Au25(SR)18 nanoparticles.
AB  - The molecular ion of the nanoparticle Au 25(SCH 2CH 2Ph) 18 (A 25(SR) 18) is
      observed at 7394 Da in fast atom bombardment (FAB, Xe atoms) ionization mass
      spectrometry using a 3-nitrobenzyl alcohol matrix. A distinctive pattern of
      positive fragment ions is evident in the mass interval 5225-7394 Da, where peaks
      are seen for successive mass losses equivalent to R 2S entities. Because the Au
      25(SCH 2CH 2Ph) 18 nanoparticle structure is crystallographically known to
      consist of a centered Au 13 icosahedral core surrounded by six Au 2(SR) 3
      semirings, the R 2S loses are proposed to represent serial rearrangements and
      decompositions of the semiring structures. Mass losses equivalent to R 2S 2 and R
      2 entities also appear at the lower end of this mass interval. The most intense
      spectral peak, at m/ z = 5246 Da, is assigned to the fragment Au 25S 10, from
      which all of the CH 2CH 2Ph organic units have been cleaved but from which no
      gold atoms have been lost. A different pattern of fragmentation is observed at
      lower masses, producing ions corresponding to serial losses of one gold atom and
      varied numbers of sulfur atoms, which continues down to a Au 9S 2 fragment. FAB
      mass spectra of the Au nanoparticle are much easier to interpret than laser
      desorption/ionization spectra, but they show more extensive fragmentation than do
      electrospray and low laser pulse intensity MALDI spectra. The loss of R 2S
      fragmentation in FAB is distinctive and unlike that seen in the other ionization
      modes. The FAB spectrum for the nanoparticle Au 25(S(CH 2) 9CH 3) 18 is also
      reported; its fragmentation parallels that for Au 25(SCH 2CH 2Ph) 18, implying
      that this nanoparticle has the same surprising stellated (staples) structure.

PMID- 18707128
TI  - Molecular basis for the structural instability of human DJ-1 induced by the L166P
      mutation associated with Parkinson's disease.
AB  - DJ-1 is a dimeric protein of unknown function in vivo. A mutation in the human DJ
      1 gene causing substitution of proline for leucine at residue 166 (L166P) has
      been linked to early onset Parkinson's disease. Lack of structural stability has
      precluded experimental determination of atomic-resolution structures of the L166P
      DJ-1 polymorph. We have performed multiple molecular dynamics (MD) simulations (
      approximately 1/3 mus) of the wild-type and L166P DJ-1 polymorph at physiological
      temperature to predict specific structural effects of the L166P substitution.
      L166P disrupted helices alpha1, alpha5, alpha6 and alpha8 with alpha8 undergoing
      particularly severe disruption. Secondary structural elements critical for
      protein stability and dimerization were significantly disrupted across the entire
      dimer interface, as were extended hydrophobic surfaces involved in dimer
      formation. Relative to wild-type DJ-1, L166P DJ-1 populated a broader ensemble of
      structures, many of which corresponded to distorted conformations. In a L166P
      dimer model the substitution significantly destabilized the dimer interface,
      interrupting >100 intermolecular contacts that are important for dimer formation.
      The L166P substitution also led to major perturbations in the region of a highly
      conserved cysteine residue (Cys-106) that participates in dimerization and that
      is critical for a proposed chaperone function of DJ-1. Cys-106 is located
      approximately 16 A from the substitution site, demonstrating that structural
      disruptions propagate throughout the whole protein. Furthermore, L166P DJ-1
      showed a significant increase in hydrophobic surface area relative to wild-type
      protein, possibly explaining the tendency of the mutant protein to aggregate.
      These simulations provide details about specific structural disturbances
      throughout L166P DJ-1 that previous studies have not revealed.

PMID- 18707130
TI  - Detection and identification of Coxiella burnetii based on the mass spectrometric
      analyses of the extracted proteins.
AB  - Rapid and reliable detection, identification, and typing of bacterial species are
      necessary in response to natural or terrorist-caused outbreaks of infectious
      diseases and play crucial roles in diagnosis and efficient treatment. We report
      here two proteomic approaches with a high potential in the detection and
      identification of Coxiella burnetii, the causative agent of Q fever. The first of
      them starts with the acetonitrile (ACN) and trichloroacetic acid extractions of
      inactivated C. burnetii cells followed by the detection of extracted molecules
      and ions derived from the inactivated cells by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. In the second approach,
      identification of the proteins extracted by ACN is accomplished after enzymatic
      digestion by electrospray tandem mass spectrometry coupled to a nanoscale
      ultraperformance liquid chromatography (LC-MS/MS). In order to observe
      morphological differences on the surface structures upon extraction, the
      inactivated and treated cells of the bacterium were examined by electron
      microscopy. The LC-MS/MS approach has allowed identification of 20 proteins in
      the ACN extracts of C. burnetii strain RSA 493 that were observed in more than 3
      out of 10 experiments.

PMID- 18707131
TI  - Hydrophobic interaction chromatography of soluble interleukin I receptor type II
      to reveal chemical degradations resulting in loss of potency.
AB  - A hydrophobic interaction chromatography method was developed to analyze
      recombinant soluble Interleukin 1 receptor type II (sIL-1R type II) drug
      substance and assess the stability of the drug under accelerated degradation
      studies. HIC resolved the degraded molecules into three peaks. A combination of
      several analytical techniques, including cyanogen bromide cleavage, reversed
      phase chromatography, mass spectrometry, and N-terminal sequencing, were used to
      identify the origins of these peaks. We found that accelerated degradation
      resulted from three different events, deamidation and isomerization at asparagine
      317 (Asn317), C-terminal cleavage, and aggregation. The iso-aspartate 317 (iso
      Asp317)-containing species were shown to elute in HIC peak I and the Asp317
      containing species in HIC peak II, respectively. Deamidation-isomerization to iso
      Asp317, but not deamidation to Asp317, resulted in altered retention time on HIC
      companied by loss of potency, presumably by introducing a significant
      conformational change. CNBr C-terminal analysis showed that the inactive HIC peak
      I consisted of sIL-1R type II with "large" C-terminal truncations of 13 or 14
      amino acids, whereas the active HIC peak II contained C-terminally full length
      and "small" C-terminal clips of two amino acids. Molecular modeling indicates
      that the short loop D317-S320, in the third domain of IL-1R type II, has a
      crucial impact on the stability of the molecule.

PMID- 18707132
TI  - Impedance method for detecting HIV-1 protease and screening for its inhibitors
      using ferrocene-peptide conjugate/Au nanoparticle/single-walled carbon nanotube
      modified electrode.
AB  - A highly sensitive screening assay based on electrochemical impedance
      spectroscopy (EIS) has been developed for detecting HIV-1 protease (PR) and
      subsequent evaluation of its corresponding inhibitors at picomolar levels. The
      assay format was based on the immobilization of the thiol terminated
      ferrocene(Fc)-pepstatin conjugate on a single-walled carbon nanotube/gold
      nanoparticle (SWCNT/AuNP) modified gold electrode. The alteration of the
      interfacial properties of electrodes upon HIV-1 PR and Fc-pepstatin conjugate
      interaction was traced by EIS. On the basis of the charge transfer resistance
      data obtained and using a mixed kinetic and diffusion model, this procedure was
      capable of detecting picomolar HIV-1 PR owing to the specific binding of this
      enzyme to Fc modified pepstatin. A competitive inhibition assay format was then
      performed using four potent HIV-1 PR inhibitors. The estimated inhibition
      constant ( K i) attested that lopinavir/ritonavir ( K i = 20 +/- 3 pM) and
      saquinavir ( K i = 57 +/- 8 pM) even at 10 pM competed strongly with pepstatin
      for effective binding to HIV-1 PR. Indinavir ( K i = 630 +/- 22 pM) only competed
      well with pepstatin at a much higher concentration (1 nM). No significant
      inhibitory effect was observed for the fosamprenavir ( K i =11 +/- 0.5 nM) as
      expected from this pro-drug. Such results agreed well with the values reported in
      the literature. This assay format is a definite asset for the expedited
      development of effective HIV-1 PR inhibitors with low molecular weights.

PMID- 18707133
TI  - Aptamer-based Au nanoparticles-enhanced surface plasmon resonance detection of
      small molecules.
AB  - Small molecules are difficult to detect by conventional SPR technique directly
      because the changes in the refractive index resulting from the binding processes
      of small biomolecules are often small. In order to extend the application of SPR
      biosensor in detecting a small molecule, we combine the advantage of aptamer
      technique with the amplifying effect of Au nanoparticles to design a sensitive
      SPR sensor for detecting small molecules. The principle of this sensor is based
      on surface inhibition detection. The aptamer is first immobilized on SPR gold
      film with its ss-DNA structure. The aptamer possessing this structure can be
      hybridized with Au nanoparticles-tagged complementary ss-DNA and result in a
      large change of SPR signal. However, the aptamer will change its structure from
      ss-DNA to tertiary structure after adenosine is added to the SPR cell. The
      aptamer possessing tertiary structure could not hybridize with Au nanoparticles
      tagged complementary ss-DNA. Thus, the change of SPR signal resulted in the
      hybridization reaction between aptamer and Au nanoparticles-tagged complementary
      ss-DNA will decrease with the increase of the number of aptamers possessing
      tertiary structure, which is proportional to the concentration of the small
      molecule. Based on this principle, we choose a simple system (antiadenosine
      aptamer/adenosine) to detect the sensing ability of this SPR biosensor for a
      small molecule. The experimental results confirm that the SPR sensor we developed
      possesses a good sensitivity and a high selectivity for adenosine. The detection
      range for adenosine is from 1 x 10 (-9) to 1 x 10 (-6) M. More significantly, it
      is fairly easy to generalize this strategy to detect a spectrum of small
      molecules by SPR spectroscopy using different aptamers. Therefore, it is expected
      that this method may offer a new direction in designing high-performance SPR
      biosensors for sensitive and selective detection of a wide spectrum of small
      molecules.

PMID- 18707134
TI  - Restraining expansion of the peak envelope in H/D exchange-MS and its application
      in detecting perturbations of protein structure/dynamics.
AB  - Hydrogen/deuterium exchange (H/DX) mass spectrometry (MS) is increasingly applied
      to problems in protein structural biology in order to map protein dynamics and
      identify sites of interactions. In theory, an MS-based readout of deuterium label
      incorporation can overcome the concentration, size, purity, and complexity
      limitations inherent in NMR-based measurements of exchange; however, in practice,
      these advantages are reduced due to spectral interference and dilution of the
      sample in deuterium oxide (D 2O). In this study, we demonstrate that popular H/DX
      labeling strategies aggravate the interference problem and that significant
      recovery of spectral capacity may be achieved with a "minimalist" strategy.
      Simulations of peptide deuteration justify large reductions in the level of D 2O
      used in labeling experiments, as well as reduced numbers of peaks used in making
      relative labeling measurements between biochemical states of a protein. To
      demonstrate the utility of a minimalist approach, calmodulin was interrogated in
      a bottom-up H/DX-MS workflow, and sensitivity to the addition of Ca (2+) as a
      structural perturbation was measured as a function of % D 2O and the number of
      peaks used in quantitating deuteration level. It is shown that high sensitivity
      to change is preserved with deuteration levels of 5.0 +/- 1.1 (apo-CaM) and 1.4
      +/- 1.3% (holo-CaM) using 10% D 2O in the labeling experiment. Further, only two
      peaks of a peptide peak distribution are needed to sensitively monitor changes in
      protein structure, dynamics, or both.

PMID- 18707135
TI  - Quantitative measurements of cell-cell signaling peptides with single-cell MALDI
      MS.
AB  - Cell-to-cell signaling peptides play important roles in neurotransmission,
      neuromodulation, and hormonal signaling. Significant progress has been achieved
      in qualitative investigations of signaling peptides in the nervous system using
      single cell matrix-assisted laser desorption/ionization mass spectrometry.
      However, quantitative information about signaling peptides is difficult to obtain
      with this approach because only small amounts of analytes are available for
      analysis. Here we describe several methods for quantitative microanalysis of
      peptides in individual Aplysia californica neurons and small pieces of tissue.
      Stable isotope labeling with d0- and d4-succinic anhydride and iTRAQ reagents has
      been successfully adopted for relative quantitation of nanoliter volume samples
      containing the Aplysia insulin C beta peptide. Comparative analysis of the C beta
      peptide release site, the upper labial nerve, and its synthesis location, the F-
      and C-clusters, shows that the release site possesses almost three times more of
      this compound. The method of standard addition permits absolute quantitation of
      the physiologically active neuropeptide cerebrin from small structures, including
      nerves and neuronal clusters, in the femtomole range with a limit of detection of
      19 fmol. The simplicity of these methods and the commercial availability of the
      reagents allow quantitative measurements from a variety of small-volume
      biological samples.

PMID- 18707136
TI  - Label-free DNA sensor by boron-doped diamond electrode using an ac impedimetric
      approach.
AB  - An electrochemical biosensor using a boron-doped diamond (BDD) electrode is
      described for differentiating between gene sequences according to DNA
      hybridization events using an ac impedimetric approach. BDD electrodes were
      dipped into a 1% solution of polyethylenimine (PEI) to adsorb a thin layer of
      positively charged PEI on the surface of BDD, then PEI-modified BDD electrodes
      were used to immobilize negatively charged single-stranded PCR fragments from
      Exon 7 of human p53 gene. Alternating current impedimetric measurements were
      first performed on these systems in phosphate buffered saline (PBS) and then upon
      exposure to single-stranded DNA (ssDNA). When the ssDNA-immobilized BDD electrode
      and solution ssDNA were completely complementary, a large drop in impedance was
      measured. Complementary DNA could be clearly detected at concentrations down to
      10 (-19) g mL (-1) at a fixed frequency (10 Hz). Higher concentrations of DNA
      gave faster hybridization with saturation occurring at levels above 1.0 pg mL (
      1.) Responses were much lower upon exposure to noncDNA, even at higher
      concentrations. The results show it is possible to directly detect target DNA at
      a fixed frequency and without additional labeling.

PMID- 18707137
TI  - Dual actions involved in arsenite-induced oxidative DNA damage.
AB  - Arsenic is a recognized human carcinogen, but the mechanism of carcinogenesis is
      not well understood. Oxidative stress and inhibition of DNA damage repair have
      been postulated as potential carcinogenic actions of arsenic. The present study
      tests the hypothesis that arsenite not only induces oxidative stress but also
      inhibits the activity of the DNA base excision repair protein, poly(ADP-ribose)
      polymerase-1 (PARP-1), leading to exacerbation of the oxidative DNA damage
      induced by arsenic. HaCat cells were treated with arsenite for 24 h before
      measuring 8-hydroxyl-2'-deoxyguanosine (8-OHdG), PARP-1 activity, and reactive
      oxygen species (ROS). Zinc supplementation and PARP-1 siRNA were used to increase
      or decrease, respectively, the PARP-1 protein's physiological function. At high
      concentrations (10 microM or higher), arsenite greatly induced oxidative DNA
      damage, as indicated by 8-OHdG formation. At lower concentrations (1 microM),
      arsenite did not produce detectable 8-OHdG, but was still able to effectively
      inhibit PARP-1 activity. Zinc supplementation reduced the formation of 8-OHdG,
      restored the PARP-1 activity inhibited by arsenite, but did not decrease ROS
      production. SiRNA knockdown of PARP-1 did not affect the 8-OHdG level induced by
      arsenic, while it greatly increased the 8-OHdG level produced by hydrogen
      peroxide indicating that PARP-1 is a molecular target of arsenite. Our findings
      demonstrate that in addition to inducing oxidative stress at higher
      concentrations, arsenite can also inhibit the function of a key DNA repair
      protein, PARP-1, even at very low concentrations, thus exacerbating the overall
      oxidative DNA damage produced by arsenite, and potentially, by other oxidants as
      well.

PMID- 18707139
TI  - Xenobiotic-activated receptors: from transcription to drug metabolism to disease.
AB  - Xenobiotic-activated receptors (XARs) are a group of ligand-activated
      transcription factors that are evolutionally specialized to regulate genomic
      programs to protect the body against innumerable chemicals from the environment.
      XARs share unique properties, such as promiscuous ligand binding, conserved
      structural motifs, common protein partners, and overlapping target genes. These
      unique features of XARs clearly distinguish them from receptors that are
      activated by endogenous chemicals to regulate energy metabolism, reproduction,
      and growth and differentiation. XARs regulate xenobiotic metabolism and
      disposition by controlling the expression and induction of drug-metabolizing
      enzymes and transporters. Furthermore, XARs integrate a broad range of protective
      mechanisms, such as antioxidative response and immune/inflammatory functions, to
      antagonize foreign chemicals. As the primary means of xenobiotic sensing and
      defense, XARs are intimately involved in drug disposition, polymorphic drug
      clearance, drug-drug interaction, and pathogenesis of some chemically induced
      cancers and chronic diseases. As a consequence, some XAR characteristics have
      been exploited in drug development and safety evaluation of drugs and
      environmental carcinogens and toxicants. In this perspective, common features and
      recent advances in the structures, modes of action, and implications in disease
      and drug development of XARs are discussed.

PMID- 18707138
TI  - Azaspiracid substituent at C1 is relevant to in vitro toxicity.
AB  - The azaspiracids are a group of marine toxins recently described that currently
      includes 20 analogues. Not much is known about their mechanism of action,
      although effects on some cellular functions have been found in vitro. We used the
      reported effects on cell viability, actin cytoskeleton, and caspase activation to
      study the structure-activity relationship of AZA-1 and AZA-2 and the role of the
      carboxylic acid moiety in toxicity. AZA-1, AZA-2, and the synthetic AZA-2-methyl
      ester (AZA-2-ME), where the C1 carboxylic acid moiety of AZA-2 was esterified to
      the corresponding methyl ester moiety, induced a reduction of cell viability in
      neuroblastoma and hepatocyte cell lines with similar potency and kinetics.
      Interestingly, the mast cell line HMC-1 was resistant to AZA-induced
      cytotoxicity. Actin cytoskeleton alterations and caspase activation appeared
      after treatment with AZA-1, AZA-2, AZA-2-ME, and biotin-AZA-2 (AZA-2 labeled with
      biotin at C1) in neuroblastoma cells with similar qualitative, quantitative, and
      kinetics characteristics. Irreversibility of AZA effects on the actin
      cytoskeleton and cell morphology after short incubations with the toxin were
      common to AZA-1, AZA-2, and AZA-2-ME; however, 10-fold higher concentrations of
      biotin-AZA-2 were needed for irreversible effects. AZA-2-ME was rapidly
      metabolized in the cell to AZA-2, while transformation of biotin-AZA-2 into AZA-2
      was less efficient, which explains the different potency in short exposure times.
      The moiety present at C1 is related to AZA toxicity in vitro. However, the
      presence of a methyl moiety at C8 is irrelevant to AZA toxicity since AZA-1 and
      AZA-2 were equipotent regardless of the readout effect.

PMID- 18707140
TI  - In vitro metabolism and covalent binding of enol-carboxamide derivatives and anti
      inflammatory agents sudoxicam and meloxicam: insights into the hepatotoxicity of
      sudoxicam.
AB  - Sudoxicam and meloxicam are nonsteroidal anti-inflammatory drugs (NSAIDs) from
      the enol-carboxamide class. While the only structural difference between the two
      NSAIDs is the presence of a methyl group on the C5-position of the 2
      carboxamidothiazole motif in meloxicam, a marked difference in their
      toxicological profile in humans has been discerned. In clinical trials, sudoxicam
      was associated with several cases of severe hepatotoxicity that led to its
      discontinuation, while meloxicam has been in the market for over a decade and is
      devoid of hepatotoxicity. In an attempt to understand the biochemical basis for
      the differences in safety profile, an in vitro investigation of the metabolic
      pathways and covalent binding of the two NSAIDs was conducted in NADPH
      supplemented human liver microsomes. Both compounds demonstrated NADPH-dependent
      covalent binding to human liver microsomes; however, the extent of binding of
      [(14)C]-meloxicam was approximately 2-fold greater than that of [(14)C]
      sudoxicam. While inclusion of glutathione (GSH) in microsomal incubations
      resulted in a decrease in covalent binding for both NSAIDs, the reduction in
      binding was more pronounced for meloxicam. Metabolite identification studies on
      [(14)C]-sudoxicam in NADPH-supplemented human liver microsomes indicated that the
      primary route of metabolism involved a P450-mediated thiazole ring scission to
      the corresponding acylthiourea metabolite (S3), a well-established pro-toxin. The
      mechanism of formation of S3 presumably proceeds via (a) epoxidation of the C4-C5
      thiazole ring double bond, (b) epoxide hydrolysis to the corresponding thiazole
      4,5-dihydrodiol derivative, which was observed as a stable metabolite (S2), (c)
      ring opening of the thiazole-4,5-dihydrodiol to an 2-oxoethylidene thiourea
      intermediate, and (d) hydrolysis of the imine bond within this intermediate to
      yield S3. In the case of meloxicam, the corresponding acylthiourea metabolite M3
      was also observed, but to a lesser extent; the main route of meloxicam metabolism
      involved hydroxylation of the 5'-methyl group, a finding that is consistent with
      the known metabolic fate of this NSAID. Inclusion of GSH led to a decrease in the
      formation of M3 with the concomitant formation of an unusual two-electron
      reduction product (metabolite M7). The formation of M7 is proposed to arise via
      reduction of the imine bond in 2-oxopropylidene thiourea, an intermediate in the
      thiazole ring scission pathway in meloxicam. In conclusion, the results of our
      analysis suggest that if the covalent binding of the two NSAIDs is important to
      the overall hepatotoxicity risk, the differences in metabolism (differential
      preponderance of formation of the acylthiourea relative to total metabolism),
      differential effects of GSH on covalent binding, and finally differences in daily
      doses of the two NSAIDs may serve as a plausible explanation for the marked
      differences in toxicity.

PMID- 18707142
TI  - Dispersant adsorption and viscoelasticity of alumina suspensions measured by
      quartz crystal microbalance with dissipation monitoring and in situ dynamic
      rheology.
AB  - Adsorption behavior and water content of adsorbed layers of four dispersants for
      aqueous ceramic processing were studied by quartz crystal microbalance with
      dissipation monitoring (QCM-D) on alumina surfaces. The dispersants were a
      poly(acrylic acid), a lignosulfonate, and two hydrophilic comb copolymers with
      nonionic polyoxyethylene chains of different molecular weights. A Voigt model was
      applied to analyze the viscoelastic behavior of the adsorbed dispersant layers.
      The results from QCM-D were compared with viscoelastic properties determined by
      in situ dynamic rheology measurements of highly concentrated alumina suspensions
      during slip casting. The QCM-D results showed that both the poly(acrylic acid)
      and the lignosulfonate adsorbed in low amounts and in a flat conformation, which
      generated thin, highly rigid layers less than 1 nm thick. The water content of
      these layers was found to be around 30% for the lignosulfonate and 35% for the
      poly(acrylic acid). High casting rate and strength in terms of storage modulus
      were observed in the final consolidate of the suspensions with the two
      polyelectrolytes. In contrast, the high molecular weight comb copolymer adsorbed
      in a less elastic layer with a thickness of about 6 nm, which is enough to
      provide steric stabilization. The viscous behavior of this layer was attributed
      to high water content, which was calculated to be around 90%. Such a water-rich
      layer gives a lubrication effect, which allows for reorientation of particles
      during the consolidation process, resulting in a high final strength of the
      ceramic material. During consolidation, the suspension showed a slow casting
      rate, most likely due to rearrangement facilitated by the lubricating layer. The
      short-chain comb copolymer adsorbed in a 1.5 nm thick, rigid layer and gave low
      final strength to the consolidated suspension. It is likely that the poor
      consolidation behavior is caused by flocculation due to insufficient
      stabilization of the dispersion.

PMID- 18707143
TI  - Observation from scanning tunneling microscopy of a striped phase for octanethiol
      adsorbed on Au(111) from solution.
AB  - A self-assembled monolayer of 1-octanethiol was prepared on a Au(111) surface via
      liquid-phase adsorption. An investigation of the surface using ultrahigh-vacuum
      scanning tunneling microscopy revealed a striped phase of the octanethiol
      molecules under the conditions examined. This phase resembles the well-known
      "pinstripe" structure of alkanethiols on Au(111), with a registry that is similar
      to that of the previously observed p x radical3 structures. We discuss the nature
      of this structure with respect to those that have been observed for other n
      alkanethiols.

PMID- 18707141
TI  - Five tyrosines and two serines in human albumin are labeled by the
      organophosphorus agent FP-biotin.
AB  - Tyrosine 411 of human albumin is an established site for covalent attachment of
      10-fluoroethoxyphosphinyl- N-biotinamidopentyldecanamide (FP-biotin),
      diisopropylfluorophosphate, chlorpyrifos oxon, soman, sarin, and dichlorvos. This
      work investigated the hypothesis that other residues in albumin could be modified
      by organophosphorus agents (OP). Human plasma was aggressively treated with FP
      biotin; plasma proteins were separated into high and low abundant portions using
      a proteome partitioning antibody kit, and the proteins were digested with
      trypsin. The FP-biotinylated tryptic peptides were isolated by binding to
      monomeric avidin beads. The major sites of covalent attachment identified by mass
      spectrometry were Y138, Y148, Y401, Y411, Y452, S232, and S287 of human albumin.
      Prolonged treatment of pure human albumin with chlorpyrifos oxon labeled Y138,
      Y150, Y161, Y401, Y411, and Y452. To identify the most reactive residue, albumin
      was treated for 2 h with DFP, FP-biotin, chlorpyrifos oxon, or soman, digested
      with trypsin or pepsin, and analyzed by mass spectrometry. The most reactive
      residue was always Tyr 411. Diethoxyphosphate-labeled Tyr 411 was stable for
      months at pH 7.4. These results will be useful in the development of specific
      antibodies to detect OP exposure and to engineer albumin for use as an OP
      scavenger.

PMID- 18707144
TI  - Drying and rehydration of DLPC/DSPC symmetric and asymmetric supported lipid
      bilayers: a combined AFM and fluorescence microscopy study.
AB  - This work characterizes the impact of lipid symmetry/asymmetry on
      drying/rehydration reorganization in phase-separated dilauroylphosphatidylcholine
      (DLPC)/distearoylphosphatidylcholine (DSPC) supported lipid bilayers (SLBs) at
      the submicron and micron-scale. In addition the prevention of major
      drying/rehydration reorganization by the use of trehalose is demonstrated. Even
      though it was found using fluorescence microscopy that micrometer scale structure
      is preserved in the presence and absence of trehalose upon drying/rehydration,
      AFM and FRAP experiments successfully revealed major changes in the phase
      separated structure such as defects, obstructions, lipid condensation, collapse
      structures, and complex incomplete DLPC-DSPC mixing/exchange in the absence of
      trehalose. In the presence of trehalose the membrane preserves its structure at
      the nanometer scale and mobility. We found that SLBs with asymmetric domain
      configurations underwent major rearrangements during drying and rehydration,
      whereas the symmetric domain configuration mainly rearranged during rehydration,
      that we hypothesize is related to lower transmembrane cohesiveness or lack of
      anchoring to the substrate in the case of the asymmetric domains.

PMID- 18707145
TI  - Integral geometry analysis of fluorescence micrographs for quantitative relative
      comparison of protein adsorption onto polymer surfaces.
AB  - Most methods developed to study protein binding to distinct surfaces can only
      determine the average amount of adsorbed protein or merely provide (qualitative)
      information on its spatial distribution. Both these features can be characterized
      rigorously by integral geometry analysis of fluorescence micrographs. This
      approach is introduced here to compare the relative protein adsorption onto
      various polymer surfaces: polystyrene (PS), poly(methyl methacrylate) (PMMA),
      poly( n-butyl methacrylate) (PnBMA), poly( tert-butyl methacrylate) (PtBMA), and
      PS(PETA) and cross-linked poly(ethylene oxide) (PEO*(PETA)), admixed with
      pentaerythritol triacrylate (PETA). The polymeric surfaces were incubated for 15
      min in phosphate-buffered saline (pH 7.4) containing 125 mug/mL fluorescently
      labeled lectins, either lentil lectin (LcH) or concanavalin A (ConA).
      Fluorescence images were recorded at identical conditions (physiological buffer,
      same exposure time, magnification, gain). For each image, taken a few times for
      each polymer, the distribution and average value of the normalized intensity were
      determined. The results show that the binding of LcH to PS(PETA), PtBMA, PS,
      PnBMA, PMMA, and PEO*(PETA) can be expressed by the ratio of the following values
      (mean +/- 95% confidence interval): 0.356 +/- 0.022, 0.298 +/- 0.030, 0.241 +/-
      0.014, 0.083 +/- 0.008, 0.039 +/- 0.008, and 0.010 +/- 0.006, respectively. In
      turn, the relative adsorption of ConA is described by the values 0.252 +/- 0.016,
      0.217 +/- 0.014, 0.222 +/- 0.016, 0.046 +/- 0.006, 0.116 +/- 0.008, and 0.006 +/-
      0.002, respectively. Low dispersions of fluorescence intensity around average
      values indicate homogeneous distribution of adsorbed proteins. The introduced
      approach enables a fast and easy way not only to quantify the relative amount of
      bound proteins but also to characterize quantitatively the organization of their
      surface distribution, as demonstrated for patchlike protein adsorption onto the
      polymer blend surface.

PMID- 18707146
TI  - Fluorophore labeling enables imaging and evaluation of specific CXCR4-ligand
      interaction at the cell membrane for fluorescence-based screening.
AB  - Development of CXCR4-specific ligands is an important issue in chemotherapy of
      HIV infection, cancer metastasis, and rheumatoid arthritis, and numerous
      potential ligands have been developed to date. However, it is difficult to assess
      their binding mode and specificity because of uncertainties in the structure of
      the CXCR4-ligand complexes. To address this problem, we have synthesized
      fluorophore labeled Ac-TZ14011, which is derived from T140, a powerful CXCR4
      antagonist. Binding of Ac-TZ14011 to CXCR4 on the cell membrane was observed by
      fluorescence microscope, and analysis of the binding data produced IC 50 values
      of several ligands comparable to those obtained in RI-based assays. This
      fluorescence-based assay is applicable to explore new pharmacophores of CXCR4
      specific ligands with high-throughput screening and also to screening of the
      other GPCR binding ligands.

PMID- 18707147
TI  - Nanoparticulate glutathione peroxidase mimics based on selenocystine-pullulan
      conjugates.
AB  - We synthesized nanoparticulate glutathione peroxidase (GPx) mimics in which
      selenocystine (SeCyst) was conjugated to a hydrophilic linear polysaccharide,
      pullulan (Pul). The SeCyst ester-conjugated Pul derivatives (SeCyst-Pul) in
      phosphate buffer (pH 7) were treated with a sonicator to spontaneously form
      particulate materials. Dynamic light scattering measurements revealed that the
      SeCyst-Pul conjugates could form particulate materials with diameters between 100
      and 300 nm. Distinctive endothermic peaks were observed for the SeCyst-Pul
      aggregate solutions based on a differential scanning calorimetric analysis. The
      tryptophan (Trp) fluorescence intensity of SeCyst benzyl ester-tryptophanyl-Pul
      (SeCyst-Bz-Trp-Pul) mostly decreased in comparison to those of the Trp-Pul (its
      precursor) and free Trp, which indicates that the Trp residues come close to each
      other during the aggregation of the conjugates. Formation of SeCyst-Pul
      aggregates could be induced by the hydrophobic interactions between the SeCyst
      esters and the amino acid residues on Pul. The GPx-like activity of SeCyst-Bz-Trp
      Pul aggregates for the reduction of H2O2 was enhanced nearly 20-fold higher than
      that of free SeCyst. The double-reciprocal plots of the SeCyst-Bz-Trp-Pul
      aggregate-catalyzed reduction yielded parallel lines by varying the substrate
      concentrations, indicating a "ping-pong" mechanism that is similar to those of
      the natural GPxs. The enhanced GPx activity of the SeCyst-Bz-Trp-Pul aggregate
      was also supported by higher kinetic parameters, k(cat)/K(m) (GSH) and
      k(cat)/K(m) H2O2. Overall, the enhanced activity of the SeCyst-Bz-Trp-Pul
      aggregate would be attributed to a hydrophobic environment that was formed at the
      vicinity of the SeCyst.

PMID- 18707148
TI  - Precursor-ion mass re-estimation improves peptide identification on hybrid
      instruments.
AB  - Mass spectrometry-based proteomics experiments have become an important tool for
      studying biological systems. Identifying the proteins in complex mixtures by
      assigning peptide fragmentation spectra to peptide sequences is an important step
      in the proteomics process. The 1-2 ppm mass-accuracy of hybrid instruments, like
      the LTQ-FT, has been cited as a key factor in their ability to identify a larger
      number of peptides with greater confidence than competing instruments. However,
      in replicate experiments of an 18-protein mixture, we note parent masses deviate
      171 ppm, on average, for ion-trap data directed identifications and 8 ppm, on
      average, for preview Fourier transform (FT) data directed identifications. These
      deviations are neither caused by poor calibration nor by excessive ion-loading
      and are most likely due to errors in parent mass estimation. To improve these
      deviations, we introduce msPrefix, a program to re-estimate a peptide's parent
      mass from an associated high-accuracy full-scan survey spectrum. In 18-protein
      mixture experiments, msPrefix parent mass estimates deviate only 1 ppm, on
      average, from the identified peptides. In a cell lysate experiment searched with
      a tolerance of 50 ppm, 2295 peptides were confidently identified using native
      data and 4560 using msPrefixed data. Likewise, in a plasma experiment searched
      with a tolerance of 50 ppm, 326 peptides were identified using native data and
      1216 using msPrefixed data. msPrefix is also able to determine which MS/MS
      spectra were possibly derived from multiple precursor ions. In complex mixture
      experiments, we demonstrate that more than 50% of triggered MS/MS may have had
      multiple precursor ions and note that spectra with multiple candidate ions are
      less likely to result in an identification using TANDEM. These results
      demonstrate integration of msPrefix into traditional shotgun proteomics workflows
      significantly improves identification results.

PMID- 18707149
TI  - Immobilized metal affinity chromatography revisited: pH/acid control toward high
      selectivity in phosphoproteomics.
AB  - Despite recent advances in instrumentation and analytical strategies for
      identification and quantitation of protein phosphorylation, a highly specific
      enrichment protocol is still a challenge in large-scale studies. Here, we report
      a simple pH/acid control method that addresses the poor specificity seriously
      criticized in IMAC. Detailed evaluation of the capture and release mechanism in
      IMAC revealed that pH, buffer and salt yield a complex interplay in enrichment of
      phosphopeptides, yet they play individual roles in recovery and specificity. A
      revised one-step IMAC method with low sample loss and high specificity can be
      rationally designed by controlling salt, pH and the structure and concentration
      of organic acid. Without methyl esterification, the one-step IMAC enrichment with
      single LC-MS/MS identified 386 phosphoproteins in 550 mug of non-small-cell lung
      cancer cell lysate with 96% specificity. Additional fractionation by SDS-PAGE
      from 4 mg of cell lysate revealed the comprehensive proteome map, identifying
      2747 phosphorylation sites from 2360 nondegenerate phosphopeptides and 1219
      phosphoproteins with a false discovery rate of 0.63%. To our knowledge, this
      pH/acid-controlled IMAC procedure provides higher specificity than any other one
      step IMAC purification procedure. Furthermore, the simple and reproducible IMAC
      protocol can be adapted to other solid supports, fully automated or manual, for
      large-scale identification of the vastly under-explored phosphoproteome.

PMID- 18707150
TI  - The construction of a bioactive peptide database in Metazoa.
AB  - Bioactive peptides play critical roles in regulating most biological processes in
      animals, and have considerable biological, medical and industrial importance. A
      number of peptides have been discovered usually based on their biological
      activities in vitro or based on their sequence similarities in silico. Through
      searches in Swiss-Prot and Trembl protein databases using BLAST alignment tools
      and other in silico methods, all currently known bioactive peptides and their
      precursor proteins are extracted. In addition, 132 recently discovered putative
      peptide genes in Drosophila as well as their orthologs in other species are
      collected. In total, 20 027 bioactive peptides from 19 438 precursor proteins
      covering 2820 metazoan species are retained, and they, respectively, make up a
      peptide and a peptide precursor database. The peptides and peptide precursor
      proteins are further classified into 373 families, 178 of which are represented
      by Prosite Pfam or Smart motifs, or by typical peptide motifs that have been
      constructed recently. The remaining 195 families are novel peptide families. The
      motifs characterizing the 178 peptide families are saved into a peptide motif
      database. The peptide, peptide precursor and peptide motif databases (version
      1.0) are the most complete peptide, precursor and peptide motif collection in
      Metazoa so far. They are available on the WWW at http://www.peptides.be/.

PMID- 18707151
TI  - Quantitative analysis of redox-sensitive proteome with DIGE and ICAT.
AB  - Oxidative modifications of protein thiols are important mechanisms for regulating
      protein functions. The present study aimed to compare the relative effectiveness
      of two thiol-specific quantitative proteomic techniques, difference gel
      electrophoresis (DIGE) and isotope coded affinity tag (ICAT), for the discovery
      of redox-sensitive proteins in heart tissues. We found that these two methods
      were largely complementary; each could be used to reveal a set of unique redox
      sensitive proteins. Some of these proteins are low-abundant signaling proteins
      and membrane proteins. From DIGE analysis, we found that both NF-kappaB
      repressing protein and epoxide hydrolase were sensitive to H 2O 2 oxidation. In
      ICAT analysis, we found that specific cysteines within sacroplasmic endoplamic
      reticulum calcium ATPase 2 and voltage-dependent anion-selective channel protein
      1 were sensitive to H 2O 2 oxidation. From these analyses, we conclude that both
      methods should be employed for proteome-wide studies, to maximize the possibility
      of identifying proteins containing redox-sensitive cysteinyl thiols in complex
      biological systems.

PMID- 18707152
TI  - Phosphorylation of SUMO-1 occurs in vivo and is conserved through evolution.
AB  - Protein dynamics is regulated by an elaborate interplay between different post
      translational modifications. Ubiquitin and ubiquitin-like proteins (Ubls) are
      small proteins that are covalently conjugated to target proteins with important
      functional consequences. One such modifier is SUMO, which mainly modifies nuclear
      proteins. SUMO contains a unique N-terminal arm not present in ubiquitin and
      other Ubls, which functions in the formation of SUMO polymers. Here, we
      unambiguously show that serine 2 of the endogenous SUMO-1 N-terminal protrusion
      is phosphorylated in vivo using very high mass accuracy mass spectrometry at both
      the MS and the MS/MS level and complementary fragmentation techniques.
      Strikingly, we detected the same phosphorylation in yeast, Drosophila and human
      cells, suggesting an evolutionary conserved function for this modification. The
      nearly identical human SUMO-2 and SUMO-3 isoforms differ in serine 2; thus, only
      SUMO-3 could be phosphorylated at this position. Our finding that SUMO can be
      modified may point to an additional level of complexity through modifying a
      protein-modifier.

PMID- 18707153
TI  - The metabolome-wide association study: a new look at human disease risk factors.

PMID- 18707154
TI  - Comparison of the membrane subproteomes during growth of a new pseudomonas strain
      on lysogeny broth medium, glucose, and phenol.
AB  - Study of the bacterial membrane proteome is a field of growing interest in the
      research of nutrient transport and processing. Pseudomonas sp. strain phDV1, a
      Gram-negative bacterium selected for its ability to degrade aromatic compounds,
      was monitored under different growth substrate conditions, using lysogeny broth
      medium (LB), glucose, and phenol as sole carbon source. The aim of this study was
      to characterize the membrane subproteomes of the Pseudomonas strain by proteomic
      means to assess the protein composition of this subcellular compartments, which
      appears fundamental for the biodegradation of aromatic compounds. A total number
      of 129 different proteins have been identified by MALDI-TOF/TOF, 19 of which are
      membrane proteins that belong to the inner membrane and 10 that belong to the
      outer membrane. Two membrane proteins were only expressed in the presence of the
      aromatic substrate. We identified a membrane protein involved in aromatic
      hydrocarbon degradation as well as a probable porin which may, in fact, function
      as an aromatic compound-specific porin. Although the presence of different
      transporters have been reported for different aromatic compounds such as toluene
      and benzoic acid, to our knowledge, these are the first phenol-inducible membrane
      transporters identified.

PMID- 18707155
TI  - DIABLA: a new screening method for the discovery of protein targets.
AB  - Dynamic isoelectric/anisotropy binding ligand assay (DIABLA) is a new method to
      identify proteins in a complex sample that bind to a molecule of interest. This
      is accomplished by first using capillary isoelectric focusing (cIEF) to separate
      the proteins in a capillary based on their isoelectric point. This separation is
      performed while the compound being tested is present in the separation buffer.
      When the proteins are focused, the entire capillary is scanned to identify
      regions of nonzero anisotropy, which are locations where the test compound is
      interacting with a focused protein band. DIABLA was demonstrated by observing the
      binding of fluorescein-tagged progesterone to an MCF-7 breast cancer cell lysate.
      The proteins were tagged with rhodamine to permit their observation and then
      focused in the presence of the tagged progesterone. Anisotropy measurements show
      that progesterone binds to six different proteins bands in the sample.

PMID- 18707156
TI  - Sorting out HIV resistance.

PMID- 18707157
TI  - Identification of differentially expressed proteins in the cervical mucosa of HIV
      1-resistant sex workers.
AB  - Novel tools are necessary to understand mechanisms of altered susceptibility to
      HIV-1 infection in women of the Pumwani Sex Worker cohort, Kenya. In this cohort,
      more than 140 of the 2000 participants have been characterized to be relatively
      resistant to HIV-1 infection. Given that sexual transmission of HIV-1 occurs
      through mucosal surfaces such as that in the cervicovaginal environment, our
      hypothesis is that innate immune factors in the genital tract may play a role in
      HIV-1 infection resistance. Understanding this mechanism may help develop
      microbicides and/or vaccines against HIV-1. A quantitative proteomics technique
      (2D-DIGE: two-dimensional difference in-gel electrophoresis) was used to examine
      cervical mucosa of HIV-1 resistant women ( n = 10) for biomarkers of HIV-1
      resistance. Over 15 proteins were found to be differentially expressed between
      HIV-1-resistant women and control groups ( n = 29), some which show a greater
      than 8-fold change. HIV-1-resistant women overexpressed several antiproteases,
      including those from the serpin B family, and also cystatin A, a known anti-HIV-1
      factor. Immunoblotting for a selection of the identified proteins confirmed the
      DIGE volume differences. Validation of these results on a larger sample of
      individuals will provide further evidence these biomarkers are associated with
      HIV-1 resistance and could help aid in the development of effective microbicides
      against HIV-1.

PMID- 18707158
TI  - Robust prediction of the MASCOT score for an improved quality assessment in mass
      spectrometric proteomics.
AB  - Protein identification by tandem mass spectrometry is based on the reliable
      processing of the acquired data. Unfortunately, the generation of a large number
      of poor quality spectra is commonly observed in LC-MS/MS, and the processing of
      these mostly noninformative spectra with its associated costs should be avoided.
      We present a continuous quality score that can be computed very quickly and that
      can be considered an approximation of the MASCOT score in case of a correct
      identification. This score can be used to reject low quality spectra prior to
      database identification, or to draw attention to those spectra that exhibit a
      (supposedly) high information content, but could not be identified. The proposed
      quality score can be calibrated automatically on site without the need for a
      manually generated training set. When this score is turned into a classifier and
      when features are used that are independent of the instrument, the proposed
      approach performs equally to previously published classifiers and feature sets
      and also gives insights into the behavior of the MASCOT score.

PMID- 18707159
TI  - Proteome analysis of membrane fractions in colorectal carcinomas by using 2D-DIGE
      saturation labeling.
AB  - Because of its high content in receptors and signaling proteins, the analysis of
      membrane fractions is critical for the study of neoplastic diseases as colorectal
      cancer. Here, we have used the new saturation labeling for 2D-DIGE analysis of
      the membrane proteome of colorectal cancer mucosal tissues. Samples from 6
      patients (tumoral and normal paired biopsies) were included in this study. Twelve
      analytical gels were performed and considered for the quantitative study and
      statistical analysis. A spot pattern analysis, by using an unsupervised
      clustering algorithm, allowed the classification of the samples according to
      similar expression patterns in tumoral and normal samples. Those proteins whose
      expression changed significantly (Student's t-test, p < 0.05) were further
      digested and characterized by mass spectrometry. Among the differentially
      expressed proteins: annexin A2, annexin A4, annexin A5, annexin A7, lamin B,
      calponin 1 and VDAC were analyzed by immunohistochemistry using tissue
      microarrays. Annexin A2, annexin A4 and VDAC appear as potential markers of
      interest for colorectal cancer diagnosis and, presumably, therapy. In summary,
      saturation labeling provides a new and sensitive tool for the analysis of scarce
      amounts of samples, allowing sample classification and direct identification of
      deregulated proteins.

PMID- 18707160
TI  - Effect of loop distortion on the stability and structural dynamics of DNA hairpin
      and dumbbell conjugates.
AB  - The thermal stability and conformational dynamics of DNA hairpin and dumbbell
      conjugates having short A-tract base pair domains connected by tri- or
      hexa(ethylene glycol) linkers is reported. The formation of stable base-paired A
      tract hairpins having oligo(ethylene glycol) linkers requires a minimum of four
      or five A-T base pairs. The formation of base-paired dumbbells having
      oligo(ethylene glycol) linkers by means of chemical ligation of nicked dumbbells
      requires a minimum of two A-T base pairs on either side of the nick. Molecular
      modeling indicates that the hexa(ethylene glycol) linker is sufficiently long to
      permit formation of strain-free loop regions and B-DNA base pair domains. In
      contrast, the tri(ethylene glycol) is too short to permit Watson-Crick base
      pairing between the bases attached to the linker. The shorter linker distorts the
      duplex, resulting in fluxional behavior in which the base pairs adjacent to the
      linker and at the open end of the hairpin dissociate on the nanosecond time
      scale. The loss of interstrand binding energy caused by these fluctuations leads
      to a difference of approximately 5 degrees C in melting temperature between EG3
      and EG6 hairpins. An analysis of the fluxional behavior of the EG3 adjacent base
      pair has been used to study the pathways for base flipping and base stacking,
      including the identification of rotated base (partially flipped) intermediates
      that have not been described previously for A-T base pairs.

PMID- 18707162
TI  - Solubility in supercritical carbon dioxide: importance of the Poynting correction
      and entrainer effects.
AB  - Gibbs ensemble Monte Carlo simulations were used to investigate the effect of
      pressure and of entrainers on the solubility of low-volatility species in CO 2.
      Two entrainers were examined, n-octane and methanol, as well as two solutes,
      hexamethylbenzene and benzoic acid. For the three pressures studied (12, 20, and
      28 MPa), the simulations demonstrate that the increase in the solubility with
      increasing pressure is mostly due to an increase in the solute's chemical
      potential (as expressed by the Poynting correction) and not due to an increase in
      the solvent strength of supercritical CO 2. The presence of an entrainer enhances
      solubility, particularly when the solute and entrainer can form hydrogen bonds.
      The solubility of benzoic acid is enhanced by an order of magnitude upon addition
      of methanol entrainer, whereas the enhancements are less than 2 for the other
      systems.

PMID- 18707163
TI  - Wetting and evaporation of binary mixture drops.
AB  - Experimental results on the wetting behavior of water, methanol, and binary
      mixture sessile drops on a smooth, polymer-coated substrate are reported. The
      wetting behavior of evaporating water/methanol drops was also studied in a water
      saturated environment. Drop parameters (contact angle, shape, and volume) were
      monitored in time. The effects of the initial relative concentrations on
      subsequent evaporation and wetting dynamics were investigated. Physical
      mechanisms responsible for the various types of wetting behavior during different
      stages are proposed and discussed. Competition between evaporation and
      hydrodynamic flow are evoked. Using an environment saturated with water vapor
      allowed further exploration of the controlling mechanisms and underlying
      processes. Wetting stages attributed to differential evaporation of methanol were
      identified. Methanol, the more volatile component, evaporates predominantly in
      the initial stage. The data, however, suggest that a small proportion of methanol
      remained in the drop after the first stage of evaporation. This residual methanol
      within the drop seems to influence subsequent wetting behavior strongly.

PMID- 18707164
TI  - Quantum mechanical studies of residue-specific hydrophobic interactions in p53
      MDM2 binding.
AB  - Quantum chemistry calculations at the levels of MP2/cc-pVDZ and MP2/cc-PVTZ have
      been carried out to study residue-specific interactions at the hydrophobic p53
      MDM2 binding interface. The result of the calculation, based on structures from
      nanosecond molecular dynamics simulation, revealed that (19)Phe, (22)Leu, and
      (23)Trp of p53 have the strongest binding interaction with MDM2 followed by
      (26)Leu and (27)Pro. The specific residues of MDM2 that have dominant binding
      interactions with p53 are specifically identified to be (51)Lys, (54)Leu,
      (62)Met, (67)Tyr, (72)Gln, (94)Lys, (96)His, and (100)Tyr. The p53-MDM2 binding
      interaction is dominated by van der Waals interaction and to a lesser degree by
      electrostatic interaction. The MP2 results are in generally good agreement with
      those from the force field calculation while the DFT/B3LYP calculation failed to
      give attractive interaction energies for certain residue-residue interactions due
      to the lack of dispersion energy.

PMID- 18707165
TI  - Cation-specific interactions with carboxylate in amino acid and acetate aqueous
      solutions: X-ray absorption and ab initio calculations.
AB  - Relative interaction strengths between cations (X = Li (+), Na (+), K (+), NH 4
      (+)) and anionic carboxylate groups of acetate and glycine in aqueous solution
      are determined. These model systems mimic ion pairing of biologically relevant
      cations with negatively charged groups at protein surfaces. With oxygen 1s X-ray
      absorption spectroscopy, we can distinguish between spectral contributions from H
      2O and carboxylate, which allows us to probe the electronic structure changes of
      the atomic site of the carboxylate group being closest to the countercation. From
      the intensity variations of the COO (-) aq O 1s X-ray absorption peak, which
      quantitatively correlate with the change in the local partial density of states
      from the carboxylic site, interactions are found to decrease in the sequence Na
      (+) > Li (+) > K (+) > NH 4 (+). This ordering, as well as the observed bidental
      nature of the -COO (-) aq and X (+) aq interaction, is supported by combined ab
      initio and molecular dynamics calculations.

PMID- 18707166
TI  - Exploring the interstitial atom in the FeMo cofactor of nitrogenase: insights
      from QM and QM/MM calculations.
AB  - Density functional theory and combined quantum mechanics and molecular mechanics
      (QM/MM) calculations have been used to explore structural features of the FeMo
      cofactor with an interstitial atom X (X = N, C, or O) and its interactions with
      CO and N 2. Predicted frequencies of the metal-bound CO, QM/MM-optimized
      geometries, and calculated redox potentials of the FeMo cofactor with different
      central ligands show that the oxygen atom is the candidate for the interstitial
      atom. Calculations on the interactions of the FeMo cofactor with CO and N 2
      reveal that there is a remarkable dependence of the binding energy on the binding
      site and the interstitial atom. Generally, the Fe2 site of the FeMo cofactor has
      stronger interactions with CO and N 2 than Fe6, and both the Fe2 and Fe6 sites in
      the N-centered and O-centered clusters of the FeMo cofactor can effectively bind
      N 2 while the coordination of N 2 to the Fe6 site of the C-centered active
      cluster is unfavorable energetically. Present results indicate that the protein
      environment is important for computational characterization of the structure of
      the FeMo cofactor and properties of the metal-bound CO and N 2 are sensitive to
      the interstitial atom.

PMID- 18707167
TI  - Enhanced transfection efficiency of multicomponent lipoplexes in the regime of
      optimal membrane charge density.
AB  - Recently, membrane charge density of lipid membranes, sigma M, has been
      recognized as a universal parameter that controls the transfection efficiency of
      complexes made of binary cationic liposomes and DNA (binary lipoplexes). Three
      distinct regimes, most likely related to interactions between complexes and
      cells, have also been identified. The purpose of this work was to investigate the
      transfection efficiency behavior of multicomponent lipoplexes in the regime of
      optimal membrane charge density (1< sigma M < 2 x 10 (-2) e/A (2)) and compare
      their performance with that of binary lipoplexes usually employed for gene
      delivery purposes. We found remarkable differences in transfection efficiency due
      to lipid composition, with maximum in efficiency being obtained when
      multicomponent lipoplexes were used to transfect NIH 3T3 cells, while binary
      lipoplexes were definitely less efficient. These findings suggested that
      multicomponent systems are especially promising lipoplex candidates. With the aim
      of providing new insights into the mechanism of transfection, we investigated the
      structural evolution of lipoplexes when interacting with anionic (cellular)
      lipids by means of synchrotron small-angle X-ray diffraction (SAXD), while the
      extent of DNA release upon interaction with anionic lipids was measured by
      electrophoresis on agarose gels. Interestingly, a clear trend was found that the
      transfection activity increased with the number of lipid components. These
      results highlight the compositional properties of carrier lipid/cellular lipid
      mixtures as decisive factors for transfection and suggest a strategy for the
      rational design of superior cationic lipid carriers.

PMID- 18707168
TI  - Synthesis and light-emitting properties of disubstituted polyacetylenes carrying
      chromophoric naphthylethynylphenyl pendants.
AB  - Poly(1-phenyl-1-alkyne)s bearing chromophoric pendants and containing alkyl
      spacers (-{(C 6H 5)CC[(CH 2) m OCOC 6H 4CCNp]} n - [P 1( m) ( m = 3, 4, 9); Np =
      1-naphthyl]) were synthesized, and the effects of structural variations on the
      optical properties, especially electroluminescence, of the polymers were
      investigated. The monomers were prepared in high yields by esterification and
      coupling reactions of n-phenyl-( n - 1)-alkyn-1-ols. Selective polymerizations of
      the 1-phenyl-1-alkyne unit of the monomers were effected by WCl 6-Ph 4Sn
      catalyst, affording polymers with high molecular weights ( M w up to 63 000) in
      high yields (up to 83%). Structures and properties of the polymers were
      characterized and evaluated by IR, NMR, TGA, UV, PL, and EL analyses. All the
      polymers are thermally very stable, losing almost no weight when heated up to 400
      degrees C. Photoexcitation of the polymer solutions induces strong blue light
      emission at 460 nm, with quantum yields up to 98%. No aggregation quenching was
      observed when the polymers were fabricated into solid films. Multilayer EL
      devices with the configuration of ITO/P 1( m):PVK/BCP/Alq 3/LiF/Al were
      fabricated, which emitted blue light with luminance up to 498 cd/m (2). The
      device performance varied with the spacer length ( m), with P 1(4) giving the
      highest external quantum efficiency of 0.47%. The value was further enhanced to
      0.86% by optimizing the layer thickness and inserting a hole-injection layer.

PMID- 18707169
TI  - Improved spin trapping properties by beta-cyclodextrin-cyclic nitrone conjugate.
AB  - Spin trapping using a nitrone and electron paramagnetic resonance (EPR)
      spectroscopy is commonly employed in the identification of transient radicals in
      chemical and biological systems. There has also been a growing interest in the
      pharmacological activity of nitrones, and there is, therefore, a pressing need to
      develop nitrones with improved spin trapping properties and controlled delivery
      in cellular systems. The beta-cyclodextrin (beta-CD)-cyclic nitrone conjugate, 5
      N-beta-cyclodextrin-carboxamide-5-methyl-1-pyrroline N-oxide (CDNMPO) was
      synthesized and characterized. 1-D and 2-D NMR show two stereoisomeric forms
      (i.e., 5S- and 5R-) for CDNMPO. Spin trapping using CDNMPO shows distinctive EPR
      spectra for superoxide radical anion (O2(*-)) compared to other biologically
      relevant free radicals. Kinetic analysis of O2(*-) adduct formation and decay
      using singular value decomposition and pseudoinverse deconvolution methods gave
      an average bimolecular rate constant of k = 58 +/- 1 M(-1) s(-1) and a maximum
      half-life of t(1/2) = 27.5 min at pH 7.0. Molecular modeling was used to
      rationalize the long-range coupling between the nitrone and the beta-CD, as well
      as the stability of the O2(*-) adducts. This study demonstrates how a
      computational approach can aid in the design of spin traps with a relatively high
      rate of reactivity to O2(*-), and how beta-CD can improve adduct stability via
      intramolecular interaction with the O2(*-) adduct.

PMID- 18707170
TI  - A chiron approach to the total synthesis of (+)-aculeatin D.
AB  - A synthesis of natural aculeatin D has been achieved, with the key stereogenic
      centers taken from inexpensive and readily available D-xylose. In elaboration of
      D-xylose into a desired form readily applicable in synthesis a previously
      misinterpreted and overlooked abnormal selectivity in hydroxyl protection was
      noticed and exploited. Protocols were developed for monotosylation of a triol
      insoluble in CH2Cl2 and "freezing" the less stable isomer (aculeatin D) at the
      PIFA-mediated oxidative spirocyclization, respectively. An unexplained
      deprotonation at a benzyl protecting group by a thermodynamically more stable
      dithiane carbanion in the literature was also addressed.

PMID- 18707171
TI  - Functionalization of the methylene bridges of the calix[6]arene scaffold.
AB  - The bromine atoms of the hexabromo calixarene derivative 3 were replaced by other
      groups under S(N)1 conditions, allowing the facile synthesis of calix[6]arene
      derivatives incorporating identical functionalities at all bridges. Heating at
      reflux a mixture of 3 and the appropriate alcohol incorporated primary and
      secondary alkoxy substituents. Hydride abstraction was observed when the reaction
      with EtOH and i-PrOH was conducted in hexafluoroisopropanol (HFIP). Solvolysis of
      3 in TFE in the presence of strong nucleophiles (such as N3(-) and aniline)
      afforded the corresponding hexaazido and hexaanilino derivatives. Hydroxyl groups
      were incorporated into the calix[6]arene scaffold via acetolysis of 3, followed
      by LiAlH4 reduction of the hexaacetate derivative obtained. Friedel-Crafts
      alkylations in the absence of Lewis acids were conducted by heating at reflux a
      mixture of 3, HFIP, and a substituted benzene derivative (e.g, m-xylene, p-methyl
      anisole, mesitylene). The calix[6]arene bridges were alkylated by heating at
      reflux a mixture of 3 and 2,4-pentanedione in TFE or HFIP. In all cases the
      reaction proceeded with high diastereoselectivity, and the major isomer isolated
      was assigned to the rc5 (i.e., all-cis) form. NMR spectroscopy indicates that the
      conformation adopted by the macrocycle possesses 3-fold symmetry (a "pinched
      cone") that is rigid in the laboratory time scale in the mesityl-substituted
      derivative.

PMID- 18707172
TI  - Solid-phase organic synthesis of polyisoprenoid alcohols with traceless sulfone
      linker.
AB  - Solid-phase organic synthesis of polyprenols with a traceless sulfone linker is
      described. The polymer-bound benezenesulfinate is first linked with the "tail"
      building blocks of isoprenyl chlorides via S-alkylation. With use of dimsyl anion
      as an appropriate base, the polymer-bound alpha-sulfonyl carbanion is generated
      and coupled with other "body" building blocks in an efficient manner. After
      repeated processes and a global palladium-catalyzed desulfonation with LiEt 3BH
      as the reducing agent, the desired polyprenols with various chain lengths and
      geometrical configurations are obtained in 32-59% overall yields. The solid-phase
      synthesis offers the advantage in facile isolation of polyprenols without tedious
      operation or time-consuming purification.

PMID- 18707173
TI  - A general, iterative, and modular approach toward carbohydrate libraries based on
      ruthenium-catalyzed oxidative cyclizations.
AB  - Carbohydrates are an omnipresent class of highly oxygenated natural products. Due
      to their wide spectra of biological activities, they have been in the center of
      synthetic organic chemistry for more than 130 years. During the past 50 years non
      natural carbohydrates attracted the interest of various chemists in the fields of
      organic, biological, and medical chemistry. Especially desoxygenated sugars
      proved to be an important class of compounds. Up to date, most non-natural
      analogues are synthesized starting from natural, enantiomerically pure
      carbohydrates in multistep synthesis. In this report, we present a synthetic
      strategy that allows the selective modular synthesis of natural and non-natural
      carbohydrates within five synthetic steps starting from readily available
      starting materials. Due to a sequential introduction of O- or N-functionalities,
      a regioselective protection of each new functional group is possible. The key
      step in the carbohydrate synthesis is a RuO4-catalyzed oxidative cyclization via
      a pH-dependent dehydrogenation-dihydroxylation-cyclization or an oxidative
      fragmentation-cyclization, leading to highly substituted new carbohydrates, in
      which each functional group is orthogonally protected and accessible for further
      synthetic operations.

PMID- 18707174
TI  - Study of an unexpected rearrangement of the alpha-phenyl pyrane derivatives
      prepared via hetero-Diels-Alder reaction of acyclic vinyl allenes and aldehydes.
AB  - The Lewis acid catalyzed hetero-Diels-Alder reaction between acyclic vinyl
      allenes and aldehydes as heterodienophiles was studied. This reaction allows for
      the preparation of pyrane derivatives in good yields, high facial and
      regioselectivity and moderate endo/exo ratio. When benzaldehyde was used as the
      heterodienophile, rearranged products were obtained depending on the reaction
      conditions. DFT calculations were used to study the rearrangement, concluding
      that it is a highly selective ionic process, driven by the stability of the
      rearranged products.

PMID- 18707175
TI  - Synthesis of a 7-azaindole by chichibabin cyclization: reversible base-mediated
      dimerization of 3-picolines.
AB  - The lithium diisopropylamide (LDA)-mediated condensation of 2-fluoro-3-picoline
      and benzonitrile to form 2-phenyl-7-azaindole via a Chichibabin cyclization is
      described. Facile dimerization of the picoline via a 1,4-addition of the
      incipient benzyllithium to the picoline starting material and fast 1,2-addition
      of LDA to benzonitrile cause the reaction to be complex. Both adducts are shown
      to reenter the reaction coordinate to produce the desired 7-azaindole. The
      solution structures of the key intermediates and the underlying reaction
      mechanisms are studied by a combination of IR and NMR spectroscopies.

PMID- 18707176
TI  - An efficient and expeditious synthesis of di- and trisubstituted amino-phenyl and
      -benzyl derivatives of tetrazole and [1,3,4]oxadiazol-2-one.
AB  - A practical protocol for the parallel synthesis and purification of amino
      tetrazole and [1,3,4]oxadiazol-2-one derivatives as carboxylic acid bioisosteres
      is described. Phenyl- and benzyl-amines, substituted with tetrazole or
      [1,3,4]oxadiazol-2-one, were transformed into functionally diverse and novel
      compounds, with p K a values ranging from 4.9 to 8.4, by two sequential reductive
      alkylation reactions. These series of di- and trisubstituted amino-phenyl and 
      benzyl derivatives were produced in solution using solid-supported reagents and
      were purified by solid-phase extraction (SPE) techniques.

PMID- 18707177
TI  - Nanomechanical resonance spectroscopy: a novel route to ultrasensitive label-free
      detection.
AB  - We propose a new chemical detection technique in which an analyte's vibrational
      frequencies are interrogated directly using an array of nanomechanical
      resonators. This "nanomechanical resonance spectroscopy" (NRS) could permit label
      free chemical detection, combining the high sensitivity of nanomechanical
      approaches with the high selectivity of traditional spectroscopy. A computational
      proof of principle is presented, demonstrating the central concept: exploiting
      resonant exchange of vibrational energy for chemical identification. Guidelines
      for experimental realization of NRS are discussed.

PMID- 18707178
TI  - Flexible piezotronic strain sensor.
AB  - Strain sensors based on individual ZnO piezoelectric fine-wires (PFWs; nanowires,
      microwires) have been fabricated by a simple, reliable, and cost-effective
      technique. The electromechanical sensor device consists of a single electrically
      connected PFW that is placed on the outer surface of a flexible polystyrene (PS)
      substrate and bonded at its two ends. The entire device is fully packaged by a
      polydimethylsiloxane (PDMS) thin layer. The PFW has Schottky contacts at its two
      ends but with distinctly different barrier heights. The I- V characteristic is
      highly sensitive to strain mainly due to the change in Schottky barrier height
      (SBH), which scales linear with strain. The change in SBH is suggested owing to
      the strain induced band structure change and piezoelectric effect. The
      experimental data can be well-described by the thermionic emission-diffusion
      model. A gauge factor of as high as 1250 has been demonstrated, which is 25%
      higher than the best gauge factor demonstrated for carbon nanotubes. The strain
      sensor developed here has applications in strain and stress measurements in cell
      biology, biomedical sciences, MEMS devices, structure monitoring, and more.

PMID- 18707179
TI  - The effects of water vapor on the CH3O2 self-reaction and reaction with HO2.
AB  - The gas phase reactions of CH3O2 + CH3O2, HO2 + HO2, and CH3O2 + HO2 in the
      presence of water vapor have been studied at temperatures between 263 and 303 K
      using laser flash photolysis coupled with UV time-resolved absorption detection
      at 220 and 260 nm. Water vapor concentrations were quantified using tunable diode
      laser spectroscopy operating in the mid-IR. The HO2 self-reaction rate constant
      is significantly enhanced by water vapor, consistent with what others have
      reported, whereas the CH3O2 self-reaction and the cross-reaction (CH3O2 + HO2)
      rate constants are nearly unaffected. The enhancement in the HO2 self-reaction
      rate coefficient occurs because of the formation of a strongly bound (6.9 kcal
      mol(-1)) HO2 x H2O complex during the reaction mechanism where the H2O acts as an
      energy chaperone. The nominal impact of water vapor on the CH3O2 self-reaction
      rate coefficient is consistent with recent high level ab initio calculations that
      predict a weakly bound CH3O2 x H2O complex (2.3 kcal mol(-1)). The smaller
      binding energy of the CH3O2 x H2O complex does not favor its formation and
      consequent participation in the methyl peroxy self-reaction mechanism.

PMID- 18707180
TI  - Quantum/classical studies of vibrationally mediated photodissociation of Ar x
      H2O.
AB  - Results of multiple configuration quantum/classical simulations of the dynamics
      of Ar x H2O photodissociation are reported. In agreement with experimental
      studies of Nesbitt and co-workers [J. Chem. Phys. 2000, 112, 7449], we find that
      the OH products emerge rotationally excited, compared to the dissociation of bare
      H2O. The wavelength dependence of the total cross section and the energy transfer
      to the argon atom are also investigated. The trends are interpreted in terms of
      features in the Ar x H2O A state potential surface.

PMID- 18707181
TI  - Charge-density-wave to Mott-Hubbard phase transition in quasi-one-dimensional
      bromo-bridged Pd compounds.
AB  - A -Pd(III)-Br-Pd(III)-Mott-Hubbard state was observed in a quasi-one-dimensional
      bromo-bridged Pd compound [Pd(en)2Br](C5-Y)2 x H2O (en = ethylenediamine, C5-Y =
      dipentylsulfosuccinate) for the first time. The phase transition between Mott
      Hubbard and charge-density-wave states occurred at 206 +/- 2 K and was confirmed
      by using X-ray, ESR, Raman and electronic spectroscopies, electrical resistivity,
      and heat capacity. From X-ray powder diffraction patterns and Raman spectra of a
      series of Pd-Br compounds, [Pd(en)2Br](C(n)-Y)2 x H2O (n = 4, 5, 6, 7, 8, 9, and
      12), chemical pressure from the alkyl chains of the counterions caused the phase
      transition.

PMID- 18707182
TI  - Monolayer control of discotic liquid crystal by electromigration of dewetted
      layers in thin film devices.
AB  - We show that ultrathin films of a semiconductive discotic liquid crystal, viz.
      phthalocyanines, can be organized to form a conductive channel tens of microns
      long between Au electrodes with thickness control over a single monolayer. Our
      approach exploits the electromigration of the isotropic phase formed starting
      from the pretransitional region of the columnar-isotropic phase transition.
      Dewetted isotropic material accumulates to the negative electrode by applying a
      longitudinal electric field of about 1 V/microm. Dewetting and electromigration
      expose an ultrathin film, a few monolayers thick, exhibiting columnar liquid
      crystal order. The layers of this ultrathin film melt progressively above T(C)
      and can be individually exfoliated by electromigration, starting from the ninth
      down to the first monolayer. The analysis of the current flowing through the
      junction as a function of the temperature, together with the comparative imaging
      of the evolution of morphology, yields a detailed picture of the changes in the
      dimensionality of the conductive phthalocyanine film and allows us to extract the
      behavior of the order parameter. The phenomenon of electromigration opens
      interesting questions on the technological control of individual monolayers on
      device patterns.

PMID- 18707183
TI  - Chemical denaturants inhibit the onset of dewetting.
AB  - The mechanism by which the aqueous cosolvents guanidinium chloride and urea
      denature proteins is a matter of controversy. Here, we use all-atom molecular
      dynamics simulations to study the effect of both denaturants on the dewetting of
      water confined between nanoseparated hydrophobic plates. It is found that the
      denaturants inhibit the onset of dewetting, so that it occurs at shorter
      interplate distances than in pure water. Our results support a role for urea and
      guanidinium in assisting in the solvation of nonpolar surfaces, thereby weakening
      hydrophobic effects known to be important for protein stability.

PMID- 18707184
TI  - Reticular synthesis of covalent organic borosilicate frameworks.
AB  - This paper reports the synthesis and characterization of a new crystalline 3D
      covalent organic framework, COF-202: [C(C6H4)4]3[B3O6 (tBuSi)2]4, formed from
      condensation of a divergent boronic acid, tetra(4-dihydroxyborylphenyl)methane,
      and tert-butylsilane triol, tBuSi(OH)3. This framework is constructed through
      strong covalent bonds (Si-O, B-O) that link triangular and tetrahedral building
      units to form a structure based on the carbon nitride topology. COF-202
      demonstrates high thermal stability, low density, and high porosity with a
      surface area of 2690 m2 g-1. The design and synthesis of COF-202 expand the type
      of linkage that could be used to crystallize new materials with extended covalent
      organic frameworks.

PMID- 18707187
TI  - A model for decision support in signal triage.
AB  - Spontaneous reporting of suspected adverse drug reactions (ADRs) has long been a
      cornerstone of pharmacovigilance. With the increasingly large volume of ADRs,
      regulatory agencies, scientific/academic organizations and marketing
      authorization holders have applied statistical tools to assist in signal
      detection by identifying disproportionate reporting relationships in spontaneous
      reporting databases. These tools have generated large numbers of signals defined
      as drug-ADR reporting associations that meet specified statistical criteria. The
      challenge is to identify which signals are most likely to be medically important
      and therefore warrant priority for further investigation. Decisions related to
      signal triage are often complex and are based on a combination of clinical,
      epidemiological, pharmacological and regulatory criteria. There are no specific
      regulations, guidelines or standards that provide an objective basis for these
      decisions. This paper describes preliminary work to identify and quantify the
      specific factors that contribute to a decision to prioritize a specific drug-ADR
      combination for further in-depth review. We applied a tool from the discipline of
      decision analysis to systematically assess the important attributes of
      spontaneously reported ADRs. A model was created that integrates these
      assessments and produces rankings for the signals generated from quantitative
      signalling methods. Although more research is necessary to evaluate the
      performance of this model fully, preliminary results suggest that the use of
      formal decision analysis approaches to support signal triage can provide
      potential benefit and will help meet an important need.

PMID- 18707188
TI  - On pharmaceutical risk minimization.
AB  - Current regulatory guidelines related to pharmaceutical risk minimization put
      most emphasis on risk communication and control of the use of drugs. Little, if
      any, consideration is given to those aspects of an adverse drug reaction that
      ultimately determine whether the risk can be minimized. However, this limited
      scope is unfortunate and could prevent risk minimization activities from
      improving drug use safety. This article attempts to present an overview of
      possible elements of pharmaceutical risk minimization and to place these in a
      framework. The promotion of drug safety through risk communication and control of
      use should be advanced, with more attention to actionable and evidence-based
      guidance relating to the 'pretreatment evaluation', and in particular the 'on
      treatment management' of the patient.

PMID- 18707189
TI  - RevAssist: a comprehensive risk minimization programme for preventing fetal
      exposure to lenalidomide.
AB  - Lenalidomide (Revlimid) is an immunomodulatory drug and an analogue of
      thalidomide, a known teratogen. To prevent fetal exposure, in the US lenalidomide
      is available only under a special restricted distribution programme called
      RevAssist. Under this risk minimization programme, only prescribers and contract
      pharmacies registered with the programme are able to prescribe and dispense the
      product. Patients must be advised of, agree to and comply with the requirements
      of the RevAssist programme in order to receive lenalidomide through a registered
      prescriber. A total of 15 584 patients were registered in the RevAssist programme
      during the first year lenalidomide was on the market. There were four reports of
      false-positive beta-human chorionic gonadotrophin measurements in patients aged
      43-57 years. Mandatory patient and prescriber surveys have shown discrepant
      responses that were resolved by risk management intervention specialists 99% of
      the time. The voluntary patient surveys have shown understanding of the risks of
      lenalidomide use and of behaviours necessary to minimize risks in >95% of females
      of childbearing potential and adult males. To date, there have been no reports of
      pregnancy in female patients or female partners of male patients. The pharmacy
      audit findings showed compliance with RevAssist was high. Although RevAssist is
      labour-intensive, time-consuming and costly, it continues to be effective in
      preventing fetal exposure to lenalidomide.

PMID- 18707191
TI  - Inhaled corticosteroids and adrenal insufficiency: prevalence and clinical
      presentation.
AB  - OBJECTIVE: Adrenal insufficiency (AI) is a potentially life-threatening
      condition. It is known that high doses of inhaled corticosteroids (ICS) can
      induce systemic adverse effects. Currently, there are no data on the prevalence
      of AI associated with the use of ICS. This study aimed to investigate the
      prevalence and clinical presentation of AI (associated or not associated with
      exogenous Cushing's syndrome) in patients who were prescribed ICS by French
      physicians during the period 2000-5. METHODS: All metropolitan French
      paediatricians, endocrinologists, pulmonologists and intensive care physicians (n
      = 11 783) were mailed questionnaires requesting information regarding cases of AI
      associated or not associated with exogenous Cushing's syndrome between 2000 and
      2005. Data collected included patient demographics, oral corticosteroid or ICS
      used during the year preceding the diagnosis of AI, underlying condition(s),
      concomitant treatment(s), presenting clinical signs and symptoms, results of
      laboratory investigations and outcome. The French pharmacovigilance database was
      screened for spontaneous reports to determine the frequency of AI associated with
      the use of ICS, using the capture-recapture method. RESULTS: Forty-six cases of
      AI were identified. Twenty-three cases presented with clinical symptoms of AI
      alone and 23 with exogenous Cushing's syndrome. ICS prescribed were fluticasone
      propionate (n = 24), budesonide (n = 12) and beclometasone dipropionate (n = 5).
      In 82% (n = 32) of cases for which data were available, ICS were prescribed at
      high doses. A potential drug interaction was found in 12 cases. Thirteen cases of
      AI were identified in the French pharmacovigilance database, one of which was
      common with the questionnaire survey. The capture-recapture method provided an
      estimation of 598 (95% CI 551, 648) cases of AI associated with the use of ICS
      for the 2000-5 period in France. CONCLUSION: The results of this study confirm
      the occurrence of adrenal insufficiency in patients treated with ICS. Although
      the prevalence of ICS-induced AI reported in this study is low, the likelihood of
      under-diagnosis underlines the need to consider this risk in patients when
      prescribing these drugs.

PMID- 18707190
TI  - Benefit-risk assessment of linezolid for serious gram-positive bacterial
      infections.
AB  - Linezolid is an oxazolidinone, a new class of antibacterial with a unique
      mechanism of action, namely inhibition of the formation of a functional 70S
      initiation complex in the 50S bacterial ribosomal subunit. Linezolid is highly
      active against multidrug-resistant Gram-positive cocci, including meticillin
      resistant Staphylococcus aureus (MRSA), vancomycin-intermediate and vancomycin
      resistant S. aureus, and vancomycin-resistant enterococci; its spectrum of
      activity also includes some anaerobic bacteria. Linezolid has been studied in
      several randomized controlled trials for the treatment of patients with community
      acquired and nosocomial pneumonia, skin and soft tissue infections (SSTIs),
      urinary tract infections and bacteraemia. The available evidence suggests that
      linezolid is at least as effective as vancomycin for patients with nosocomial
      pneumonia, and there are some retrospective analyses supporting its superiority
      in comparison with vancomycin for MRSA nosocomial pneumonia, including ventilator
      associated pneumonia. Linezolid is more effective than glycopeptides, macrolides
      and beta-lactams for SSTIs. The limited available data for the treatment of
      patients with bacteraemia suggest that it may be a better treatment option than
      vancomycin and beta-lactams for these patients, but questions have arisen
      regarding patients with catheter-related bacteraemias. Compared with other
      antibacterials, linezolid is associated with a greater frequency of adverse
      events, mainly nausea, vomiting, diarrhoea and headaches. Thrombocytopenia also
      occurs more frequently in patients taking linezolid but there is no increased
      frequency of anaemia. Other adverse events potentially related to linezolid
      therapy include fungal infections (moniliasis), hypertension and serotonin-like
      syndrome, tongue discolouration and taste alterations, dizziness, insomnia, rash
      and Clostridium difficile-related diarrhoea. The majority of adverse events
      develop after prolonged administration (i.e. >2 weeks) and subside shortly after
      discontinuation of linezolid. Peripheral or optic neuropathy, another possible
      adverse effect, is associated with an even longer duration of treatment (3-6
      months). In conclusion, linezolid is an important treatment option for the
      treatment of patients with multidrug-resistant, Gram-positive bacterial
      infections. However, in order to reduce the possibility of development of
      resistance and preserve its activity, the use of linezolid should be restricted
      to treatment of patients with infections associated with high morbidity and
      mortality, particularly those caused by multidrug-resistant bacteria.

PMID- 18707192
TI  - Risk of hypospadias in offspring of women using loratadine during pregnancy: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Loratadine, a second-generation antihistamine, is commonly used to
      treat seasonal allergies. Some studies have suggested that use of loratadine by
      pregnant women increases the risk of hypospadias in male offspring. OBJECTIVE:
      This meta-analysis was designed to assess the strength of the association between
      loratadine and hypospadias. METHODS: To locate pertinent articles published in
      any language from January 1989 until August 2007, we searched electronic
      databases (MEDLINE, OVID, EMBASE, SCOPUS, TOXLINE Special, ReproTox, TERIS,
      CINAHL and others), conference proceedings and bibliographies. Studies were
      eligible for this analysis if they were cohort, case-control or case series
      studies that reported the incidence of hypospadias in the offspring of women who
      were or were not exposed to loratadine during pregnancy. Two authors
      independently extracted information on study design, participant characteristics,
      measures of outcome, control for potential confounding factors and risk estimates
      using a standardized data collection form. The Newcastle-Ottawa Scale was then
      used to assess the quality of each study. We used a random-effects meta-analysis
      model to combine the risk data. RESULTS: In 1402 potentially relevant titles, we
      found three case-control studies and seven cohort studies that reported the
      incidence of hypospadias or other congenital malformations in offspring of women
      who did or did not use loratadine during pregnancy. Together the studies in our
      meta-analysis provided information about 453 053 male births in Brazil, Canada,
      Denmark, Israel, Italy, Sweden, the UK and the US.Of 2694 male infants born to
      women using loratadine, 39 (1.4%) had hypospadias. Of 450 413 male infants born
      to women not using loratadine, 4231 (0.9%) had hypospadias. Women who used
      loratadine during pregnancy were not significantly more likely to have a son with
      hypospadias (unadjusted odds ratio [OR] 1.27, 95% CI 0.73, 2.23; adjusted OR
      1.28, 95% CI 0.69, 2.39). CONCLUSION: The results of our systematic review and
      meta-analysis of controlled observational studies indicate that the use of
      loratadine during pregnancy does not significantly increase the risk of
      hypospadias in male offspring.

PMID- 18707193
TI  - Risk factors associated with adverse drug reactions following hospital admission:
      a prospective analysis of 907 patients in two German university hospitals.
AB  - BACKGROUND: Since the 1970s, studies have examined potential risk factors
      associated with adverse drug reactions (ADRs) in a variety of settings. However,
      no pharmacoepidemiological study exists that incorporates clinical and laboratory
      parameters in a multiple regression model in order to consider predictors for
      ADRs. OBJECTIVES: To characterize risk factors associated with ADRs in patients
      admitted to university hospital departments of internal medicine. DESIGN AND
      SETTING: Intensive pharmacovigilance was carried out in departments of internal
      medicine of two university hospitals. All admissions were followed prospectively
      for the occurrence of ADRs by members of a pharmacoepidemiological team
      consisting of physicians, pharmacologists and pharmacists. To identify patients
      at high risk for experiencing ADRs, patient histories and several clinical and
      laboratory data, determined at the time of admission, were taken into
      consideration. In addition to the drug prescribed, 40 parameters defined vital
      status at admission. These included temperature, heart rate, blood pressure
      (systolic-diastolic), body mass index, nicotine and alcohol use, and first
      laboratory test results after admission on nutrition status, inflammation, liver,
      kidney, pancreas or thyroid status, electrolytes, blood count and coagulation.
      RESULTS: 907 patients were observed during the study period. The mean age of the
      study population was 60 +/- 16 years. The median number of different drugs
      administered per patient during hospitalization was 9.6 +/- 7.7. In 345 patients,
      592 ADRs were evaluated: 33.4% possible, 61.5% probable and 4.7% highly probable.
      Two ADR-related deaths were observed during the study period. Analysing ADR
      predictors, 17 of 40 parameters reached significance in univariate analysis, but
      only five in a multivariate binary regression model: raised temperature (odds
      ratio [OR] 1.609; 95% CI 1.133, 2.285), low erythrocyte levels (OR 0.386; 95% CI
      0.194, 0.768), low thrombocyte levels (OR 0.788, 95% CI 0.627, 0.989), high
      number of drugs (OR 1.117; 95% CI 1.076, 1.159) and female sex (OR 1.562; 95% CI
      0.785, 2.013) were independent predictors for ADRs. CONCLUSION: For the patients
      investigated, of the large number of clinical data available only five
      independent factors predict ADR occurrence. Taking these results into account,
      physicians will be able to focus early on patients at risk for ADRs. To minimize
      ADR occurrence, ADR predictors should be integrated into the clinical pathway.

PMID- 18707194
TI  - Advice on drug safety in pregnancy: are there differences between commonly used
      sources of information?
AB  - BACKGROUND AND OBJECTIVE: Safety regarding use in pregnancy is not established
      for many drugs. Inconsistencies between sources providing drug information can
      give rise to confusion with possible therapeutic consequences. Therefore, it is
      important to measure clinically important differences between drug information
      sources. The objective of this study was to compare two easily accessible
      Norwegian sources providing advice on drug safety in pregnancy - the product
      monographs in the Felleskatalog (FK), published by the pharmaceutical companies,
      and the five regional Drug Information Centres (DICs) in Norway - in addition to
      assessing the frequency of questions regarding drug safety in pregnancy made to
      the DICs according to the Anatomical Therapeutic Chemical (ATC) classification
      system. METHODS: Advice on drug use in pregnancy provided by the DICs in 2003 and
      2005 were compared with advice in the product monographs for the respective drugs
      in the FK. Comparison of advice was based on categorization to one of four
      categories: can be used, benefit-risk assessment, should not be used, or no
      available information. RESULTS: A total of 443 drug advice were categorized.
      Seven out of ten of drugs frequently enquired about, according to the ATC system,
      were drugs acting on the nervous system (group N). For 208 (47%) of the drugs,
      advice differed between the DICs and FK. Advice from the FK was significantly (p
      < 0.01) more restrictive than advice from the DICs. There were no differences in
      the level of consistency of advice between drugs that were newly introduced and
      those that had been on the market for a longer time, advice regarding use of
      drugs in the first trimester and advice regarding use of drugs in the second or
      third trimester, or between advice provided during 2003 and during 2005.
      CONCLUSIONS: The results of this study show considerable differences between two
      Norwegian sources providing advice on the use of drugs in pregnancy. Based on the
      knowledge that healthcare providers choose sources of information in a random
      manner, our results may be of clinical importance. We believe that the problem
      with heterogeneous drug information on this subject is not confined to Norway and
      that our results should be of international interest.

PMID- 18707195
TI  - Stimulus coding rules for perceptual learning.
AB  - Perceptual learning of visual features occurs when multiple stimuli are presented
      in a fixed sequence (temporal patterning), but not when they are presented in
      random order (roving). This points to the need for proper stimulus coding in
      order for learning of multiple stimuli to occur. We examined the stimulus coding
      rules for learning with multiple stimuli. Our results demonstrate that: (1)
      stimulus rhythm is necessary for temporal patterning to take effect during
      practice; (2) learning consolidation is subject to disruption by roving up to 4 h
      after each practice session; (3) importantly, after completion of temporal
      patterned learning, performance is undisrupted by extended roving training; (4)
      roving is ineffective if each stimulus is presented for five or more consecutive
      trials; and (5) roving is also ineffective if each stimulus has a distinct
      identity. We propose that for multi-stimulus learning to occur, the brain needs
      to conceptually "tag" each stimulus, in order to switch attention to the
      appropriate perceptual template. Stimulus temporal patterning assists in tagging
      stimuli and switching attention through its rhythmic stimulus sequence.

PMID- 18707196
TI  - Funding regimes and the implications for delivering quality palliative care
      nursing within residential aged care units in Australia.
AB  - INTRODUCTION:  BACKGROUND: Funding to Australian residential aged care units has
      undergone recent reforms. Parallel with these fiscal developments, the Australian
      Government commissioned the Guidelines for a Palliative Approach in Residential
      Aged Care that addressed the inequities of service associated with dying in
      residential aged care. AIMS: This literature review describes the variances in
      funding between Australian residential aged care facilities (RACFs), and multi
      purpose services (MPSs) and, in doing so, exposes the impact that funding
      variances have on the delivery of end-of-life and palliative care to residents in
      aged care units. FINDINGS: Government funding policy allowed RACFs an opportunity
      to adopt and implement the guidelines and standards, through funding individual
      resident identified healthcare needs. By comparison, MPSs are funded through an
      agreed (government and organisation) number of beds to provide nursing care to
      residents. This funding allocation forms MPSs' general consolidated revenue for
      service delivery. KEY ISSUES: RACFs identify nursing care needs of residents
      through a residential classification scale, while management of MPSs allocates
      funding to service provision. CONCLUSIONS: The significant factor of funding beds
      (MPS) not the delivery of nursing care required by residents (RACFs) does impact
      on the implementation of a palliative approach for residents and, hence, the
      delivery of quality nursing care. Nursing management should consider funding
      implications when allocating resources to services in MPSs.

PMID- 18707197
TI  - Remote Doctors Radiation Licence Training and Manual: a review process towards
      enhanced professional development.
AB  - CONTEXT: In the Australia Northern Territory (NT), the health service and
      especially Royal Darwin Hospital (RDH) faces many unique and special challenges
      related to the diversity of its population and its remoteness. The NT population
      is vast and varied, both culturally and geographically, and there are long
      distances between communities. Represented among the many cultures present in the
      NT are Anglo-Saxon, Mediterranean, Middle Eastern and African, and Aboriginal
      people. The Aboriginal population spans many different cultural beliefs and
      languages, depending on their geographic location. One initiative to address such
      health service challenges was the introduction of a permit system to enable
      doctors to perform limited numbers of X-rays in the NT's remote and rural
      communities. Implemented by the Radiographer Registration Board of the NT, this
      initiative allows for people in remote areas to be diagnosed and treated in their
      home community. It also prevents the unnecessary medical evacuation of patients
      to RDH, particularly when no abnormality is detected on initial imaging. The
      strategy greatly reduces social, emotional and economic costs. ISSUE: This
      article addresses the process involved in modernising and updating a vital aspect
      of the program, the 1981 Radiographic Procedures Manual, provided to doctors as a
      reference while studying in Darwin and for use on return to their communities.
      The revision process included consultation with senior radiology staff,
      previously trained doctors and senior academics. Associated issues and challenges
      are discussed, as are the results of questionnaires about doctors' satisfaction
      with the manual. LESSONS LEARNED: The unique health issues present in the NT
      demand unique solutions to minimise the social, cultural and financial impact of
      health care on those involved.

PMID- 18707198
TI  - Pre-triage procedures in mobile rural health clinics in Ethiopia.
AB  - CONTEXT: Our medical team of 12 people conducted a series of mobile health
      clinics sponsored by an indigenous relief organization in rural Ethiopia.
      Coordinating with local health authorities, the purpose of these clinics was to
      provide acute care medical treatment and public health teaching. ISSUE:
      Initially, we used a 'pre-triage' process that had evolved over a series of
      previous rural mobile clinic trips. This process involved the lead physician and
      a nurse-translator moving through the crowd selecting prospective patients based
      on appearance and responses to simple questions. A significant problem arose when
      a large crowd of people, desperate to be seen, disrupted the process and
      jeopardized the safety of our team. We subsequently developed a process that used
      an introductory session, introducing the team and describing the process of
      patient selection. We also modified the pre-triage process by involving more
      people in patient selection. In subsequent clinics, this new process was well
      accepted and contributed to increased efficiency and an overall improved
      community outreach. LESSONS LEARNED: After experiencing an adverse situation, we
      developed a system for patient selection that was well accepted and efficient. We
      found that it was essential to set expectations regarding the purpose of the
      mobile clinic and the scope of problems that could be treated. This was best done
      at the outset of the clinic in coordination with local health authorities. In
      actual patient selection, or pre-triage, we found it advantageous to enlist the
      participation of the crowd and to send several clinicians among those wishing to
      be seen for medical care. This new approach to patient selection became an
      essential element in the success of our mobile health outreach.

PMID- 18707200
TI  - Abstracts of IFCC WorldLab. Fortaleza, Italy. September 28-October 2, 2008.

PMID- 18707220
TI  - Redox control of endothelial function and dysfunction: molecular mechanisms and
      therapeutic opportunities.
AB  - The endothelium is essential for the maintenance of vascular homeostasis. Central
      to this role is the production of endothelium-derived nitric oxide (EDNO),
      synthesized by the endothelial isoform of nitric oxide synthase (eNOS).
      Endothelial dysfunction, manifested as impaired EDNO bioactivity, is an important
      early event in the development of various vascular diseases, including
      hypertension, diabetes, and atherosclerosis. The degree of impairment of EDNO
      bioactivity is a determinant of future vascular complications. Accordingly,
      growing interest exists in defining the pathologic mechanisms involved.
      Considerable evidence supports a causal role for the enhanced production of
      reactive oxygen species (ROS) by vascular cells. ROS directly inactivate EDNO,
      act as cell-signaling molecules, and promote protein dysfunction, events that
      contribute to the initiation and progression of endothelial dysfunction.
      Increasing data indicate that strategies designed to limit vascular ROS
      production can restore endothelial function in humans with vascular
      complications. The purpose of this review is to outline the various ways in which
      ROS can influence endothelial function and dysfunction, describe the redox
      mechanisms involved, and discuss approaches for preventing endothelial
      dysfunction that may highlight future therapeutic opportunities in the treatment
      of cardiovascular disease.

PMID- 18707221
TI  - Functional adaptation to loading of a single bone is neuronally regulated and
      involves multiple bones.

PMID- 18707222
TI  - Linkage screen for BMD phenotypes in male and female COP and DA rat strains.
AB  - Because particular inbred strains of experimental animals are informative for
      only a subset of the genes underlying variability in BMD, we undertook a genome
      screen to identify quantitative trait loci (QTLs) in 828 F(2) progeny (405 males
      and 423 females) derived from the Copenhagen 2331 (COP) and dark agouti (DA)
      strains of rats. This screen was performed to complement our study in female
      Fischer 344 (F344) and Lewis (LEW) rats and to further delineate the factors
      underlying the complex genetic architecture of BMD in the rat model.
      Microsatellite genotyping was performed using markers at an average density of 20
      cM. BMD was measured by pQCT and DXA. These data were analyzed in the R/qtl
      software to detect QTLs acting in both sexes as well as those having sex-specific
      effects. A QTL was detected in both sexes on chromosome 18 for midfemur
      volumetric BMD (vBMD; genome-wide, p < 0.01). On distal chromosome 1, a QTL was
      found for femur and vertebral aBMD as well as distal femur vBMD, and this QTL
      appears distinct from the proximal chromosome 1 QTL impacting BMD in our F344/LEW
      cross. Additional aBMD and vBMD QTLs and several sex-specific QTLs were also
      detected. These included a male-specific QTL (p < 0.01) on chromosome 8 and a
      female-specific QTL on chromosomes 7 and 14 (p < 0.01). Few of the QTLs
      identified showed overlap with the significant QTLs from the F344/LEW cross.
      These results confirm that the genetic influence on BMD in the rat model is quite
      complex and would seem to be influenced by a number of different genes, some of
      which have sex-specific effects.

PMID- 18707224
TI  - Identification, expression pattern, and characterization of mouse glutaredoxin 2
      isoforms.
AB  - Glutaredoxin 2 (Grx2) is a glutathione-dependent oxidoreductase involved in the
      maintenance of mitochondrial redox homeostasis. Grx2 was first characterized as
      mitochondrial protein, but alternative mRNA variants lacking the transit peptide
      encoding first exon were demonstrated for human and proposed for mouse. We
      systematically screened for alternative transcript variants of mouse Grx2. We
      identified a total of six exons, three constitutive (II, III, and IV), two
      alternative first exons (exons Ia and Ic), and one single-cassette exon (exon
      IIIb) located between exons III and IV. Exons Ic and IIIb are not present in the
      human genome; mice lack human exon Ib. The six exons give rise to five transcript
      variants that encode three protein isoforms: mitochondrial Grx2a, a cytosolic
      isoform that is homologous to the cytosolic/nuclear human Grx2c and present in
      specific cells of many tissues and the testis-specific isoform Grx2d that is
      unique to mice. Mouse Grx2c can form an iron/sulfur cluster-bridged dimer, is
      enzymatically active as a monomer, and can donate electrons to ribonucleotide
      reductase. Testicular cells lack mitochondrial Grx2a but contain cytosolic Grx2.
      Prominent immunostaining was detected in spermatogonia and spermatids. These
      results provide evidence for additional functions of Grx2 in the cytosol, in cell
      proliferation, and in cellular differentiation.

PMID- 18707225
TI  - Biological basis of bone formation, remodeling, and repair-part III:
      biomechanical forces.
AB  - While it has been long appreciated that biomechanical forces are involved in bone
      remodeling and repair, the actual mechanism by which a physical force is
      translated to the corresponding intracellular signal has largely remained a
      mystery. To date, most biomechanical research has concentrated upon the effect on
      bone morphology and architecture, and it is only recently that the complex
      cellular and molecular pathways involved in this process (called
      mechanotransduction) are being described. In this paper, we review the current
      understanding of bone mechanobiology and highlight the implications for clinical
      medicine and tissue engineering research.

PMID- 18707223
TI  - PPARG by dietary fat interaction influences bone mass in mice and humans.
AB  - Adult BMD, an important risk factor for fracture, is the result of genetic and
      environmental interactions. A quantitative trait locus (QTL) for the phenotype of
      volumetric BMD (vBMD), named Bmd8, was found on mid-distal chromosome (Chr) 6 in
      mice. This region is homologous to human Chr 3p25. The B6.C3H-6T (6T) congenic
      mouse was previously created to study this QTL. Using block haplotyping of the 6T
      congenic region, expression analysis in the mouse, and examination of
      nonsynonymous SNPs, peroxisome proliferator activated receptor gamma (Pparg) was
      determined to be the most likely candidate gene for the Bmd8 QTL of the 630 genes
      located in the congenic region. Furthermore, in the C3H/HeJ (C3H) strain, which
      is the donor strain for the 6T congenic, several polymorphisms were found in the
      Pparg gene. On challenge with a high-fat diet, we found that the 6T mouse has a
      lower areal BMD (aBMD) and volume fraction of trabecular bone (BV/TV%) of the
      distal femur compared with B6 mice. Interactions between SNPs in the PPARG gene
      and dietary fat for the phenotype of BMD were examined in the Framingham
      Offspring Cohort. This analysis showed that there was a similar interaction of
      the PPARG gene and diet (fat intake) on aBMD in both men and women. These
      findings suggest that dietary fat has a significant influence on BMD that is
      dependent on the alleles present for the PPARG gene.

PMID- 18707227
TI  - Spatial regulation of BMP signaling by patterned receptor expression.
AB  - Local delivery of TGF-beta/BMP ligands is commonly used as a tissue engineering
      strategy for the spatial regulation of cell growth and differentiation. While the
      location and the dose of ligand are the only parameters that influence the
      spatial distribution and biological effects of the ligand in vitro, in vivo
      genetic studies of development reveal that spatial control of TGF-beta/BMP
      signaling can be accomplished at multiple levels, from ligand release to signal
      interpretation. Here we focus on spatial control of BMP signaling by patterned
      receptor expression. Motivated by our recent experimental analysis of the two
      dimensional BMP signaling patterns in the developing Drosophila egg, we formulate
      one- and two-dimensional models of ligand diffusion and internalization in the
      presence of patterned receptor expression. Our analysis of these models shows
      that they can capture the quantitative features of the experimentally observed
      pattern of phosphorylated SMAD in Drosophila oogenesis and shows that patterned
      receptor expression provides versatile control of BMP signaling in developing
      tissues. Quantitative understanding of the mechanisms of spatiotemporal control
      of signaling pathways in development is essential for successful harnessing of
      these pathways in tissue engineering.

PMID- 18707226
TI  - Oxidative stress in the regulation of normal and neoplastic hematopoiesis.
AB  - Recent evidence suggests that oxidative stress contributes significantly to the
      regulation of hematopoietic cell homeostasis. In particular, red blood cells and
      hematopoietic stem cells are highly sensitive to deregulated accumulation of
      reactive oxygen species (ROS). Unchecked ROS accumulation often leads to
      hemolysis, that is, to destruction and shortened life span of red blood cells. In
      addition, the process of erythroid cell formation is sensitive to ROS
      accumulation. Similarly, ROS buildup in hematopoietic stem cells compromises
      their function as a result of potential damage to their DNA leading to loss of
      quiescence and alterations of hematopoietic stem cell cycling. These
      abnormalities may lead to accelerated aging of hematopoietic stem cells or to
      hematopoietic malignancies.

PMID- 18707228
TI  - Tube formation in Drosophila egg chambers.
AB  - The reorganization of epithelial sheets into tubes is a fundamental process in
      the formation of many organs, such as the lungs, kidneys, gut, and neural tube.
      This process involves the patterning of distinct cell types and the coordination
      of those cells during the shape changes and rearrangements that produce the tube.
      A better understanding of the cellular and genetic mechanisms that regulate tube
      formation is necessary for tissue engineers to develop functional organs in
      vitro. The Drosophila egg chamber has emerged as an outstanding model for
      studying tubulogenesis. Synthesis of the dorsal respiratory appendages by the
      follicular epithelium resembles primary neurulation in vertebrates. This review
      summarizes work on the patterning and morphogenesis of the dorsal-appendage tubes
      and highlights key areas where mathematical modeling could contribute to our
      understanding of these processes.

PMID- 18707231
TI  - The currency and tempo of extinction.
AB  - This study examines estimates of extinction rates for the current purported
      biotic crisis and from the fossil record. Studies that compare current and
      geological extinctions sometimes use metrics that confound different sources of
      error and reflect different features of extinction processes. The per taxon
      extinction rate is a standard measure in paleontology that avoids some of the
      pitfalls of alternative approaches. Extinction rates reported in the conservation
      literature are rarely accompanied by measures of uncertainty, despite many
      elements of the calculations being subject to considerable error. We quantify
      some of the most important sources of uncertainty and carry them through the
      arithmetic of extinction rate calculations using fuzzy numbers. The results
      emphasize that estimates of current and future rates rely heavily on assumptions
      about the tempo of extinction and on extrapolations among taxa. Available data
      are unlikely to be useful in measuring magnitudes or trends in current extinction
      rates.

PMID- 18707229
TI  - Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous
      scaffold (HANFS) amalgam.
AB  - Degeneration of the intervertebral disc (IVD) represents a significant
      musculoskeletal disease burden. Although spinal fusion has some efficacy in pain
      management, spine biomechanics is ultimately compromised. In addition, there is
      inherent limitation of hardware-based IVD replacement prostheses, which
      underscores the importance of biological approaches to disc repair. In this
      study, we have seeded multipotent, adult human mesenchymal stem cells (MSCs) into
      a novel biomaterial amalgam to develop a biphasic construct that consisted of
      electrospun, biodegradable nanofibrous scaffold (NFS) enveloping a hyaluronic
      acid (HA) hydrogel center. The seeded MSCs were induced to undergo chondrogenesis
      in vitro in the presence of transforming growth factor-beta for up to 28 days.
      The cartilaginous hyaluronic acid-nanofibrous scaffold (HANFS) construct
      architecturally resembled a native IVD, with an outer annulus fibrosus-like
      region and inner nucleus pulposus-like region. Histological and biochemical
      analyses, immunohistochemistry, and gene expression profiling revealed the time
      dependent development of chondrocytic phenotype of the seeded cells. The cells
      also maintain the microarchitecture of a native IVD. Taken together, these
      findings suggest the prototypic potential of MSC-seeded HANFS constructs for the
      tissue engineering of biological replacements of degenerated IVD.

PMID- 18707232
TI  - Inferring developmental modularity from morphological integration: analysis of
      individual variation and asymmetry in bumblebee wings.
AB  - Organisms are built from distinct modules, which are internally coherent but
      flexible in their relationships among one another. We examined morphological
      variation within and between two candidate modules: the fore- and hindwings of
      bumblebees (Hymenoptera: Apidae: Bombus empatiens). We used the techniques of
      geometric morphometrics (Procrustes superimposition) to analyze the variation of
      landmark configurations in fore- and hindwings. Regression was used to correct
      for size-related shape variation (allometry). Principal component analysis
      revealed patterns of variation that were remarkably similar for individual
      variation and fluctuating asymmetry (FA). Because covariation of FA among parts
      must be due to direct transmission of the developmental perturbations causing FA,
      this agreement of patterns suggests that much of individual variation is also due
      to direct developmental interactions within each developing wing. Moreover,
      partial least squares analysis indicated that the patterns of shape covariation
      between fore- and hindwings were nearly the same as the patterns of within-wing
      variation. Shape covariation of FA was only found in bees that had been reared
      under elevated CO(2) concentration but not in bees from the control treatment,
      suggesting that the mechanisms of developmental interactions between fore- and
      hindwings are related to gas exchange. We conclude that the fore- and hindwings
      are developmental modules that maintain internal coherence through direct
      developmental interactions and are connected to each other only by relatively few
      links that use the system of interactions within modules.

PMID- 18707233
TI  - Toward ecologically scaled landscape indices.
AB  - Nature conservation is increasingly based on a landscape approach rather than a
      species approach. Landscape planning that includes nature conservation goals
      requires integrated ecological tools. However, species differ widely in their
      response to landscape change. We propose a framework of ecologically scaled
      landscape indices that takes into account this variation. Our approach is based
      on a combination of field studies of spatially structured populations
      (metapopulations) and model simulations in artificial landscapes. From these, we
      seek generalities in the relationship among species features, landscape indices,
      and metapopulation viability. The concept of ecological species profiles is used
      to group species according to characteristics that are important in
      metapopulations' response to landscape change: individual area requirements as
      the dominant characteristic of extinction risk in landscape patches and dispersal
      distance as the main determinant of the ability to colonize patches. The
      ecological profiles and landscape indices are then integrated into two
      ecologically scaled landscape indices (ESLI): average patch carrying capacity and
      average patch connectivity. The field data show that the fraction of occupied
      habitat patches is correlated with the two ESLI. To put the ESLI into a
      perspective of metapopulation persistence, we determine the viability for six
      ecological profiles at different degrees of habitat fragmentation using a
      metapopulation model and computer-generated landscapes. The model results show
      that the fraction of occupied patches is a good indicator for metapopulation
      viability. We discuss how ecological profiles, ESLI, and the viability threshold
      can be applied for landscape planning and design in nature conservation.

PMID- 18707234
TI  - Inferring the origins of state-dependent courtship traits.
AB  - We examine a simple model of state-dependent (indicator) traits that focuses on
      their evolutionary origins as courtship signals. A necessary condition for the
      initial evolution of signals was found: the marginal female preference for
      minimal traits must exceed a certain threshold, where that threshold is
      proportional to the marginal male fitness costs for minimal traits. We interpret
      a positive threshold as implying a need for preexisting sensory bias in order to
      overcome the threshold if indicator signals are to start to evolve. We extend the
      model to allow for the possibility that signal costs and female preferences may
      vary over evolutionary time. If there is independent information on the way that
      signaling costs have evolved, then one may use measurements of contemporary
      female preferences to make inferences concerning the presence of the ancestral
      threshold. It is the marginal female preferences for minimal male traits that are
      important, whereas reconstructing ancestral origins from measurement of average
      size signals is not informative. Our analyses suggest two foci for future
      studies: measurement of the marginal response of contemporary females to minimal
      male signals and reconstruction of how signaling costs have changed over
      evolutionary time.

PMID- 18707235
TI  - Spatial patterns and persistence of woody plant species in ecological
      communities.
AB  - The role of stochastic effects and seed dispersal limitations in maintaining the
      diversity of a tree community is investigated by means of a forest growth
      simulator called TROLL. This simulator makes it possible to investigate impacts
      on the spatial distribution and the extinction probability of plant species. I
      present the results of a two-species competition scenario. Coexistence is found
      to be possible for competitively dissimilar species, and the criterion for this
      coexistence is given analytically in the reaction-diffusion approximation. A
      higher frequency of tree falls implies a smaller extinction probability of least
      adapted species. The multispecies model is also investigated. A mathematical
      quantity-the persistence function-permits measurement of the ability of a species
      to out compete other species locally. This quantity is compared with the average
      time to extinction, and it is computed for the TROLL simulator. I interpret the
      shape of this function in light of available information on the persistence
      function in simple interacting particle systems. These results indicate an
      analogy between the dynamics of forest communities and a simple discrete and
      spatially explicit model, the voter model. The ecological implications of this
      analogy are discussed and are extended to species-rich communities.

PMID- 18707236
TI  - The effect of dominance on food hoarding: a game theoretical model.
AB  - Many food hoarding animals live in small groups structured by rank. The presence
      of conspecifics in the hoarding area increases the risk of losing stored
      supplies. The possibility of stealing from others depends on a forager's rank in
      the group. Highly ranked individuals can steal from subordinates and also protect
      their own caches. Since storing incurs both costs and benefits, the optimal
      hoarding investment will differ between individuals of different rank. In a game
      theoretical model, we investigate how dominant and subordinate individuals should
      optimize their hoarding effort. Our model imagines animals that are large-scale
      hoarders in autumn and dependent on stored supplies for winter survival. Many
      examples can be found in the bird families Paridae and Corvidae, but the model
      can be used for any hoarding species that forage in groups. Predictions from the
      model are as follows: First, subordinates should store more than dominants, but
      in a predictable environment, this difference will decrease as the environment
      gets harsher. Under harsh conditions, dominants should store almost as much as
      subordinates and, later, spend almost as much time retrieving their own caches as
      subordinates. Second, if on the other hand, bad winter conditions were not
      expected when storing, dominants should spend more time pilfering caches from
      subordinates. Third, in populations that are highly dependent on stored supplies,
      dominants should store relatively more than in populations that are less
      dependent on stored supplies. Fourth, harsher environments will favor hoarding.
      And finally, if dominant individuals store, it implies that hoarders have a
      selfish recovery advantage over conspecific pilferers.

PMID- 18707237
TI  - Simulation models of the interactions between herbivore foraging strategies,
      social behavior, and plant community dynamics.
AB  - Herbivory often operates through a feedback in which herbivores affect the
      success and location of plants, which in turn affects the foraging behavior of
      animals. Factors other than food, such as social behavior, may influence the
      interactions between herbivores and the plants they consume. We used a simulation
      model to compare the effects of foraging and social behavior on plant
      distribution and foraging efficiency by gophers (Thomomys bottae) in a system
      characteristic of California grasslands. In this system, annual forbs are the
      preferred food items, and their abundance increases in areas disturbed by gopher
      burrowing. In addition, gopher social interactions generate buffer zones between
      adjacent burrows. During the first year of the simulations, before gophers
      affected the plant community, feeding efficiency declined with increased gopher
      density. However, after 40 yr, annual plant abundance increased with increasing
      gopher density, yielding higher maximum gopher density and per capita foraging
      efficiency. Conversely, increased width of the buffer zones lowered maximum
      gopher density and annual plant abundance resulting in lower feeding efficiency.
      In addition, the compact burrow structure of gophers employing an area-restricted
      search strategy allowed a higher density of gophers to coexist, resulting in
      higher annual plant abundance and higher per capita food-capture rates.

PMID- 18707238
TI  - Latitudinal gradients in colony size for social insects: termites and ants show
      different patterns.
AB  - On the basis of a comparison of Nearctic and Neotropical ants, social insects
      have been proposed to show a latitudinal gradient in colony size. Further, the
      "fasting endurance hypothesis," which predicts larger colonies in areas with
      extended periods of low food availability, was proposed as the mechanism driving
      the gradient. To test the generality of the pattern and its mechanism, we
      examined the relationships between termite colony size and both latitude and
      annual evapotranspiration, a measure of plant productivity. We found no evidence
      that colony size increases with increasing latitude or decreasing plant
      productivity. We conclude that the pattern identified for ants cannot be
      generalized to include social insects as a whole. As is the case for
      ecogeographic gradients in insect body sizes, a pattern that is reported for one
      taxon may not be consistent for other taxa at the global level.

PMID- 18707239
TI  - Prevalence of multidrug-resistant pulmonary tuberculosis in counties with
      different duration of DOTS implementation in rural China.
AB  - AIMS: This study aimed to describe the prevalence of drug-resistant tuberculosis
      (TB) among pulmonary TB patients in rural China and to determine the extent of
      multidrug-resistant TB (MDR-TB) circulating in areas with varied duration of
      Directly Observed Treatment, Short Course (DOTS) implementation. METHODS: A cross
      sectional study was conducted in two rural counties in eastern China: Deqing with
      over 10 years' DOTS implementation and Guanyun under its second year of DOTS. The
      subjects were all culture-positive pulmonary TB patients newly diagnosed or re
      treated during 12 months of 2004-2005. The proportion method was used for drug
      susceptibility testing. RESULTS: Among the 399 subjects, 283 were new TB cases
      and 116 were previously treated. The rates of overall resistance (i.e.,
      resistance to at least one drug) in new cases were 50.4% (67) and 63.4% (95),
      respectively, in Deqing and Guanyun (p = 0.028), and 67.3% (33) and 83.6% (56),
      respectively, in previously treated cases (p = 0.0410). The rates of MDR-TB in
      new cases were 3.8% (5) in Deqing and 14.7% (22) in Guanyun (p = 0.0018), and
      16.3% (8) and 34.3% (23) in previously treated cases (p = 0.0305). CONCLUSIONS:
      Newly diagnosed and previously treated TB patients from the short-term DOTS
      covered county were at higher risk for overall drug-resistance TB and MDR-TB.
      Standardized diagnosis and treatment strategies for drug-resistant TB are
      urgently needed for effective control of MDR-TB in rural China.

PMID- 18707240
TI  - Antimicrobial effects of varied combinations of meropenem, sulbactam, and
      colistin on a multidrug-resistant Acinetobacter baumannii isolate that caused
      meningitis and bacteremia.
AB  - Meropenem (MEM; 2 g/8 hr; minimum inhibitory concentration [MIC] = 256 mg/L) plus
      sulbactam (SUL; 1 g/8 hr; MIC = 128 mg/L) (two-drug-therapy period), and
      subsequent additional intravenous colistin (COL; 2.5 mg/kg/12 hr) and
      intraventricular (COL, 5 mg/day; MIC = 1 mg/L) (three-drug-therapy period) were
      sequentially used in a patient with postneurosurgery bacteremic meningitis due to
      a multidrug-resistant Acinetobacter baumannii (MDRAB) isolate (AB(1)). We
      detected 4- to 32-fold increases in peak or trough cerebrospinal fluid
      bactericidal titer and serum bactericidal titer in three-drug-therapy period when
      comparing to those in two-drug-therapy period. The time-kill study with MEM, SUL,
      and COL alone or varied combinations (all at 1 x MIC) against AB(1) and another
      genetically nonrelated MDRAB isolate (AB(134) [MICs of MEM = 64 mg/L, SUL = 16
      mg/L, and COL = 1 mg/L]) was performed. The two-drug combinations (MEM + SUL, MEM
      + COL, and SUL + COL) each elicited different inhibitory effect on AB(1) and
      AB(134) at 6 hr. Bacterial regrowth at 24 hr was observed in the experiments in
      which the MDRAB isolate was inhibited earlier by COL alone (AB(1) and AB(134)),
      by MEM plus SUL (AB(1)), and by MEM plus COL (AB(134)), but not in SUL plus COL,
      and MEM + SUL + COL. Combined use of COL with MEM and/or SUL may provide good
      therapeutic options, even though MEM and SUL are in vitro resistance to the
      MDRAB.

PMID- 18707241
TI  - The proline-rich region of HIV-1 Nef affects CXCR4-mediated chemotaxis in Jurkat
      T cells.
AB  - T-cell chemotaxis constitutes an essential function of the immune response, since
      active secretion of chemokines controls homing and recruitment of leukocytes into
      tissues. Modification of chemotactic responses by HIV-1 may provide a mechanism
      to increase viral spread, and may be an important factor in HIV-1 disease
      progression and pathogenesis. One potent T-cell chemoattractant is SDF-1 alpha,
      the natural ligand for the HIV-1 co-receptor CXCR4. In addition, the HIV-1 gp120
      molecule shares the chemotactic properties of several chemokines, including SDF-1
      alpha. HIV-1 Nef is a pathogenic determinant and a virulence factor that has
      pleiotropic effects on immune cell processes and receptor signaling. In this
      study, the effects of Nef on T-cell migration to SDF-1 alpha, and on CXCR4
      receptor signaling were examined. We report that disruption of the proline-rich
      region of Nef inhibits T-cell migration to SDF-1 alpha. This dominant negative
      effect indicates that Nef occupies a position in the CXCR4-mediated signaling
      pathway that is upstream of an SH3-dependent pathway. The results suggest that
      Nef may play an important role in homing of T cells during viral invasion in HIV
      1 disease.

PMID- 18707242
TI  - Visible lasers were better than invisible lasers in accelerating burn healing on
      diabetic rats.
AB  - OBJECTIVE: This study was designed to assess and compare the efficacy of
      accelerating burn healing in diabetic rats using low-power visible and invisible
      lasers. BACKGROUND DATA: Low-level laser therapy (LLLT) has been used in a number
      of diabetic animal and human studies, with both positive and no effects.
      MATERIALS AND METHODS: Male Sprague-Dawley rats were used in the study.
      Streptozotocin (70 mg/kg) was given for diabetes induction. A burn wound was
      created on the shaved back of the animals using a metal rod heated to 600 degrees
      C. The study was performed using 532-, 633-, 670-, 810-, and 980-nm diode lasers.
      Incident doses of 5, 10, 20, and 30 J/cm(2) and a treatment schedule of three
      times per week were used in the experiments. The burned areas on all rats were
      measured and plotted on a chart, and the slope values (mm(2)/d) and the
      percentages of burn healing were compared. RESULTS: The percentage of burn
      healing on diabetic rats after LLLT was 78.37% for the visible lasers and 50.68%
      for the invisible lasers. There was a significant difference (p < 0.005) between
      visible lasers and invisible lasers in the percentage of burn healing on diabetic
      rats after laser therapy. CONCLUSION: LLLT at the appropriate treatment
      parameters can accelerate burn healing on diabetic rats using both visible and
      invisible lasers. The effects of visible lasers were better than those of
      invisible lasers in accelerating burn healing on diabetic rats in this study.

PMID- 18707243
TI  - A triplex ribozyme expression system based on a single hairpin ribozyme.
AB  - Triplex ribozyme (RZ) configurations allow for the individual activity of trans
      acting RZs in multiple expression cassettes (multiplex), thereby increasing
      target cleavage relative to conventionally expressed RZs. Although hairpin RZs
      have been advantageously compared to hammerhead RZs, their longer size and
      structural features complicated triplex design. We present a triplex expression
      system based on a single hairpin RZ with transcleavage capability and simple
      engineering. The system was tested in vitro using cis- and trans-cleavage kinetic
      assays against a known target RNA from HPV-16 E6/E7 mRNA. Single and multiplex
      triplex RZ constructs were more efficient in cleaving the target than tandem
      cloned hairpin RZs, suggesting that the release of individual RZs enhanced trans
      cleavage kinetics. Multiplex systems constructed with two different hairpin RZs
      resulted in better trans-cleavage compared to standard double-RZ constructs. In
      addition, the triplex RZ performed cis- and trans-cleavage in cervical cancer
      cells. The use of triplex configurations with multiplex RZs permit differential
      targeting of the same or different RNA, thus improving potential use against
      unstable targets. This prototype will provide the basis for the development of
      future RZ-based therapies and technologies.

PMID- 18707244
TI  - Focal lesions in acute mild traumatic brain injury and neurocognitive outcome: CT
      versus 3T MRI.
AB  - Mild traumatic brain injury (mTBI) is associated with long-term cognitive
      deficits. This study compared the detection rate of acute post-traumatic focal
      lesions on computed tomography (CT) and 3T (Tesla) magnetic resonance (MR)
      imaging with neurocognitive outcomes. Adults (n = 36; age range, 19-52 years)
      with a single episode of mTBI (Glasgow Coma Scale 13-15, as well as loss of
      consciousness and post-traumatic amnesia) were prospectively enrolled and had CT
      within 24 h of injury and 3T MR within 2 weeks of injury. The CT and MR scans
      were reviewed by two neuroradiologists who were blinded to clinical information.
      Twenty-eight of these mTBI subjects and 18 matched healthy volunteers also
      underwent serial neurocognitive testing. Of the 36 mTBI cases, intraparenchymal
      lesions were detected in 18 CT and 27 acute MR exams, consisting of hemorrhagic
      traumatic axonal injury (TAI) (eight CT, 17 MR), non-hemorrhagic TAI (zero CT,
      four MR), and cerebral contusions (13 CT, 21 MR). Mild TBI patients had
      significantly worse performance on working memory tasks than matched controls at
      the acute time point (<2 weeks), and at 1 month and at 1 year post-injury; yet
      there was no significant correlation of imaging findings with working memory
      impairment. In conclusion, 3T MR detected parenchymal lesions in 75% of this mTBI
      cohort with loss of consciousness and post-traumatic amnesia, a much higher rate
      than CT. However, the CT and 3T MR imaging findings did not account for cognitive
      impairment, suggesting that newer imaging techniques such as diffusion tensor
      imaging are needed to provide biomarkers for neurocognitive and functional
      outcome in mTBI.

PMID- 18707245
TI  - Apolipoprotein E3/E3 genotype decreases the risk of pituitary dysfunction after
      traumatic brain injury due to various causes: preliminary data.
AB  - Traumatic brain injury (TBI) is a devastating public health problem which may
      result in hypopituitarism. However, the mechanisms and the risk factors
      responsible for hypothalamo-pituitary dysfunction due to TBI are still unclear.
      Although APO E is one of the most abundant protein in hypothalamo-pituitary
      region, there is no study investigating the relation between APO E polymorphism
      and TBI-induced hypopituitarism. This study was undertaken to determine whether
      APO E genotypes modulate the pituitary dysfunction risk after TBI due to various
      causes, including traffic accident, boxing, and kickboxing. Ninety-three patients
      with TBI (mean age, 30.61 +/- 1.25 years) and 27 healthy controls (mean age,
      29.03 +/- 1.70 years) were included in the study. Pituitary functions were
      evaluated, and APO E genotypes (E2/E2; E3/E3; E4/E4; E2/E3; E2/E4; E3/E4) were
      screened. Twenty-four of 93 subjects (25.8%) had pituitary dysfunction after TBI.
      The ratio of pituitary dysfunction was significantly lower in subjects with APO
      E3/E3 (17.7%) than the subjects without APO E3/E3 genotype (41.9%; p = 0.01), and
      the corresponding odds ratio was 0.29 (95% confidence interval [CI], 0.11-0.78).
      In conclusion, this study provides strong evidence for the first time that APO E
      polymorphism is associated with the development of TBI-induced pituitary
      dysfunction. Present data demonstrated that APO E3/E3 genotype decreases the risk
      of hypopituitarism after TBI. The demonstration of the association between the
      APO E polymorphism and TBI may provide a new point of view in this field and
      promote further studies.

PMID- 18707247
TI  - Can varying inbreeding depression select for intermediary selfing rates?
AB  - We study the evolution of the self-fertilization of an annual hermaphroditic
      plant under varying inbreeding depression. While classical population genetic
      models treat inbreeding depression as a constant parameter, recent empirical
      research has shown that changing environmental conditions can make inbreeding
      depression vary. Here, we create a simple phenotypic model, assuming variable
      inbreeding depression. We investigate how different types of variability
      (spatial, temporal, and spatiotemporal variability) affect the evolution of
      selfing rates in three models. Two main results, which differ from the classical
      predictions, emerge from this study. First, we find that fluctuating
      environments, which influence the magnitude of inbreeding depression, are able to
      select for evolutionarily stable intermediary selfing rates. Second, we show that
      spatiotemporal variation of inbreeding depression can lead to the development and
      the maintenance of polymorphic selfing rates within a population.

PMID- 18707248
TI  - Self-similarity and the relationship between abundance and range size.
AB  - Patterns in the relationships among the range, abundance, and distribution of
      species within a biome are of fundamental interest in ecology. A self-similarity
      condition, imposed at the community level and previously demonstrated to lead to
      the power-law form of the species-area relationship, is extended to the species
      level and shown to predict testable power-law relationships between range size
      and both species abundance and area of census cell across scales of spatial
      resolution. The predicted slopes of plots of log(range size) versus
      log(abundance) are shown to be in good agreement with data from British breeding
      bird and mammal censuses and with data on the distribution of fern species in old
      growth forest. The predicted slopes of plots of log(range size) versus log (area
      of census cell) are consistent with the limited available data for British plant
      species. Self-similarity provides a testable theoretical framework for a unified
      understanding of patterns among the range, abundance, and distribution of
      species.

PMID- 18707249
TI  - Optimal size and number of propagules: allowance for discrete stages and effects
      of maternal size on reproductive output and offspring fitness.
AB  - Existing optimality models of propagule size and number are not appropriate for
      many organisms. First, existing models assume a monotonically increasing
      offspring fitness/propagule size relationship. However, offspring survival during
      certain stages may decrease with increasing propagule size, generating a peaked
      offspring fitness/propagule size function (e.g., egg size in oxygen-limited
      aquatic environments). Second, existing models typically do not consider maternal
      effects on total reproductive output and the expression of offspring
      survival/propagule size relationships. However, larger females often have greater
      total egg production and may provide better habitats for their offspring. We
      develop a specific optimality model that incorporates these effects and test its
      predictions using data from salmonid fishes. We then outline a general model
      without assuming specific functional forms and test its predictions using data
      from freshwater fishes. Our theoretical and empirical results illustrate that,
      when offspring survival is negatively correlated with propagule size, optimal
      propagule size is larger in better habitats. When larger females provide better
      habitats, their optimal propagule size is larger. Nevertheless, propagule number
      should increase more rapidly than propagule size for a given increase in maternal
      size. In the absence of density dependence, females with greater relative
      reproductive output (i.e., for a given body size) should produce more but not
      larger propagules.

PMID- 18707250
TI  - Steroid hormones and immune function: experimental studies in wild and captive
      dark-eyed juncos (Junco hyemalis).
AB  - Monogamous and polygynous male songbirds generally differ in their breeding
      season profiles of circulating testosterone. Testosterone level spikes early in
      the breeding season of monogamists and then declines, but it remains high in
      polygynists. Male dark-eyed juncos (Junco hyemalis) are socially monogamous and
      exhibit the usual pattern, but experimental maintenance of high testosterone
      throughout the breeding season alters normal behavior and physiology and affects
      various components of annual reproductive success but not overall annual success.
      Because stabilizing selection predicts that alteration of naturally existing
      phenotypes should reduce lifetime reproductive success, we asked whether
      prolonged testosterone exposure might impair immune function and perhaps thereby
      reduce life span. We assessed immune function in captive and wild male juncos
      that we treated with either testosterone-filled or empty Silastic implants.
      Results indicate that prolonged elevation of testosterone suppresses antibody
      production in captive males and cell-mediated immunity in wild males. Together
      these results suggest that testosterone-treated males may be more susceptible to
      disease or parasitic infection. As earlier studies have shown, levels of
      corticosterone as well as testosterone are higher in testosterone-treated males,
      so it is unclear whether the immune suppression we observed is due to
      testosterone's direct effects on immunity or testosterone's influence on
      glucocorticoid production. We discuss results in the context of recent hypotheses
      regarding life-history theory and potential endocrine-immune interactions.

PMID- 18707251
TI  - Energy budgets, growth rates, and thermal constraints: toward an integrative
      approach to the study of life-history variation.
AB  - Variation in thermal constraints on activity has been hypothesized to be an
      important ecological source of geographic variation in growth rates of juvenile
      eastern fence lizards Sceloporus undulatus. However, most of the evidence to
      support this hypothesis is either inferential or indirect. In this study, I
      quantitatively compared thermal constraints on activity and their relationship to
      growth rates of free-ranging juvenile fence lizards from two extremes of the
      range of variation in growth rate (Nebraska and New Jersey) used in a reciprocal
      transplant experiment. I also examined energy allocation made to growth and
      storage by yearling lizards. Reduced growth rates in New Jersey of normally fast
      growing hatchlings from Nebraska were associated with a more stringent thermal
      constraint on activity corresponding to a 2-3-h shorter predicted daily activity
      period in New Jersey compared to Nebraska. The thermal constraint on activity was
      particularly strong (24% less time available in New Jersey compared to Nebraska)
      during the period when hatchling lizards emerge (August-October). An 8% reduction
      in total activity time available over the course of a single year was associated
      with a 7% reduction in the total amount of energy accumulated by lizards in New
      Jersey. Differences in the total amount of energy available for allocation were
      also accompanied by differences in how energy was allocated. Lizards from New
      Jersey had an allocatable energy pool of approximately 40.34 kJ (88% to growth,
      12% to storage, and 0% to reproduction). Lizards from Nebraska had an allocatable
      pool of 43.44 kJ (22% to growth, 18% to storage, and 60% to reproduction). This
      study joins others in advocating and illustrating an integrative approach to
      determining the causes and consequences of life-history variation by combining
      experimental, comparative, and phylogenetic methods in a single system.

PMID- 18707252
TI  - When to press on or turn back: dispersal strategies for reef fish larvae.
AB  - Events that occur during the pelagic larval stage are thought to be important
      determinants of reef fish population dynamics. Recent research contradicts the
      early paradigm of larvae being advected as passive propagules and indicates that
      many late stage larvae have well-developed sensory and locomotory capabilities.
      Whether and how larvae use these capabilities to influence their dispersal is
      unknown. We compare alternative hypotheses regarding larval behavior. Contrary to
      the trend in dispersal modeling, we focus on larval biology rather than physical
      oceanographic considerations. Specifically, we present two streams of models: one
      that describes a return-based strategy and one in which dispersal is a central
      component. The models depend on different sets of behavioral assumptions for a
      pomacentrid species and for acanthurids, two groups with contrasting early life
      histories. Whether dispersal or return-based strategies are favored depends on
      the efficiency and sustainability of larval swimming methods and the
      environmental conditions experienced during dispersal. We argue that dispersal
      models should consider a variety of behavioral hypotheses and that the
      sensitivity of results to the behavioral assumptions made should be quantified.

PMID- 18707253
TI  - Are unusually colored eggs a signal to potential conspecific brood parasites?
AB  - It has previously been suggested that some species of birds make the last egg in
      their clutch pale as a signal to potential conspecific brood parasites that
      incubation has commenced. Here, we use game theory to show that the signaling
      function of pale eggs can be evolutionarily stable and resistant to cheating and
      to demonstrate that such a signal can only be maintained under strict conditions.
      The key conditions are, first, that there is a cost associated with the
      production of pale eggs (in particular, the cost of a pale egg produced early in
      the clutch must be more expensive than the cost of one produced later in the
      clutch) and, second, that the cost of making the last egg pale is not too great
      (relative to the costs of parasitism). We discuss the likelihood of these
      conditions being met in real systems and suggest empirical tests that would
      differentiate this theory from alternative nonadaptive explanations for pale
      eggs.

PMID- 18707254
TI  - The logic of territory choice: implications for conservation and source-sink
      dynamics.

PMID- 18707256
TI  - Microevolution in an electronic microcosm.
AB  - The evolution of microbial populations in simple environments such as chemostats
      is still not fully understood. The classical interpretation of adaptation
      involves a process of successive substitution whereby a new dominant genotype
      arises by mutation from the genotype previously dominant and spreads more or less
      rapidly through the population until it is nearly fixed. The population is, thus,
      nearly uniform most of the time. Some observations suggest that the process may
      be more complicated, but it remains formidably difficult to assemble the
      phylogeny of an evolving culture in sufficient detail to be sure. We report
      experiments with an electronic microcosm inhabited by self-replicating computer
      programs whose phylogeny can be rendered completely transparent. The physiology
      of these programs is different in many respects from that of organic creatures,
      but their population biology has many features in common, including a very
      extensive, if not unbounded, range of variation. Experimental populations evolved
      through point mutations (many of which were quasi-neutral when they were viable)
      and through rearrangements that led to a change in genome size and often had
      large effects on fitness. As a general rule, smaller genomes execute fewer
      instructions in order to replicate, the rate of replication increases as the
      number of instructions executed declines, and the rate of replication in pure
      culture is a good predictor of success in mixture. When cultured with CPU
      (central processing unit) time as the sole limiting resource, smaller genomes,
      therefore, evolve as a correlated response to natural selection for faster
      replication. The genetic basis of adaptation was highly contingent and always
      differed in replicate experiments. The pattern of evolution depends on mutation
      rate. At low mutation rates of 0.01 per genome per generation or less, we
      observed classic periodic selection, with each dominant genotype descending from
      the previous dominant and rising to a frequency of 0.8 or more. At higher
      mutation rates of about 0.1 per genome per generation, the most abundant
      genotypes rarely exceeded a frequency of about 0.4, and rare genotypes present in
      a few copies comprised a large part of the population. New dominant genotypes did
      not usually descend directly from previous dominants but, instead, from one of
      the many rare or moderately abundant genotypes. We suggest that the conventional
      chemostat paradigm may hold only as a special case at very low mutation rates and
      that the dynamics and diversity of evolving populations, even in the simplest
      conditions, may be more complex than is usually recognized. Artificial genetic
      autoadaptive systems are likely to be useful in constructing theory for
      situations that lie beyond the boundary of conventional population genetics.

PMID- 18707257
TI  - Fundamental unpredictability in multispecies competition.
AB  - One of the central goals of ecology is to predict the distribution and abundance
      of organisms. Here, we show that, in ecosystems of high biodiversity, the outcome
      of multispecies competition can be fundamentally unpredictable. We consider a
      competition model widely applied in phytoplankton ecology and plant ecology in
      which multiple species compete for three resources. We show that this competition
      model may have several alternative outcomes, that the dynamics leading to these
      alternative outcomes may exhibit transient chaos, and that the basins of
      attraction of these alternative outcomes may have an intermingled fractal
      geometry. As a consequence of this fractal geometry, it is impossible to predict
      the winners of multispecies competition in advance.

PMID- 18707258
TI  - Evolution of migration rate in a spatially realistic metapopulation model.
AB  - We use an individual-based, spatially realistic metapopulation model to study the
      evolution of migration rate. We first explore the consequences of habitat change
      in hypothetical patch networks on a regular lattice. If the primary consequence
      of habitat change is an increase in local extinction risk as a result of
      decreased local population sizes, migration rate increases. A nonmonotonic
      response, with migration rate decreasing at high extinction rate, was obtained
      only by assuming very frequent catastrophes. If the quality of the matrix habitat
      deteriorates, leading to increased mortality during migration, the evolutionary
      response is more complex. As long as habitat patch occupancy does not decrease
      markedly with increased migration mortality, reduced migration rate evolves.
      However, once mortality becomes so high that empty patches remain uncolonized for
      a long time, evolution tends to increase migration rate, which may lead to an
      "evolutionary rescue" in a fragmented landscape. Kin competition has a
      quantitative effect on the evolution of migration rate in our model, but these
      patterns in the evolution of migration rate appear to be primarily caused by
      spatiotemporal variation in fitness and mortality during migration. We apply the
      model to real habitat patch networks occupied by two checkerspot butterfly
      (Melitaea) species, for which sufficient data are available to estimate
      rigorously most of the model parameters. The model-predicted migration rate is
      not significantly different from the empirically observed one. Regional variation
      in patch areas and connectivities leads to regional variation in the optimal
      migration rate, predictions that can be tested empirically.

PMID- 18707259
TI  - Alternative food, switching predators, and the persistence of predator-prey
      systems.
AB  - Sigmoid functional responses may arise from a variety of mechanisms, one of which
      is switching to alternative food sources. It has long been known that sigmoid
      (Holling's Type III) functional responses may stabilize an otherwise unstable
      equilibrium of prey and predators in Lotka-Volterra models. This poses the
      question of under what conditions such switching-mediated stability is likely to
      occur. A more complete understanding of the effect of predator switching would
      therefore require the analysis of one-predator/two-prey models, but these are
      difficult to analyze. We studied a model based on the simplifying assumption that
      the alternative food source has a fixed density. A well-known result from optimal
      foraging theory is that when prey density drops below a threshold density,
      optimally foraging predators will switch to alternative food, either by including
      the alternative food in their diet (in a fine-grained environment) or by moving
      to the alternative food source (in a coarse-grained environment). Analyzing the
      population dynamical consequences of such stepwise switches, we found that
      equilibria will not be stable at all. For suboptimal predators, a more gradual
      change will occur, resulting in stable equilibria for a limited range of
      alternative food types. This range is notably narrow in a fine-grained
      environment. Yet, even if switching to alternative food does not stabilize the
      equilibrium, it may prevent unbounded oscillations and thus promote persistence.
      These dynamics can well be understood from the occurrence of an abrupt (or at
      least steep) change in the prey isocline. Whereas local stability is favored only
      by specific types of alternative food, persistence of prey and predators is
      promoted by a much wider range of food types.

PMID- 18707260
TI  - Disturbance regimes and life-history evolution.
AB  - Disturbance regimes are ecologically important, but many of their evolutionary
      consequences are poorly understood. A model is developed here that combines the
      within- and among-season dynamics of disturbances with evolutionary life-history
      theory. "Disturbance regime" is defined in terms of disturbance timing,
      frequency, predictability, and severity. The model predicts the optimal body size
      and time at which organisms should abandon a disturbance-prone growth habitat by
      maturing and moving to a disturbance-free, nongrowth habitat. The effects of both
      coarse-grained (those affecting the entire population synchronously) and fine
      grained disturbances (those occurring in a patch dynamics setting) are explored.
      Several predictions are congruent with previous theory. Infrequent or temporally
      unpredictable disturbances should have little effect on the evolution of life
      history strategies, even though they may cause high mortality. Similar to
      seasonal time constraints on reproduction, disturbance regimes can synchronize
      metamorphosis within a population, resulting in a seasonal decline in body size
      at maturity. Other model predictions are novel. When disturbances cause high
      mortality, coarse-grained disturbances have a much stronger effect on life
      history strategies than fine-grained disturbances, suggesting that population
      structure (relative to the scale of disturbance) plays a critical evolutionary
      role when disturbances are severe. When within-population variance in juvenile
      body size is high, two consecutive seasonal declines in body size at maturity can
      occur, the first associated with disturbance regime and the second associated
      with seasonal time constraints.

PMID- 18707261
TI  - Invasion by extremes: population spread with variation in dispersal and
      reproduction.
AB  - For populations having dispersal described by fat-tailed kernels (kernels with
      tails that are not exponentially bounded), asymptotic population spread rates
      cannot be estimated by traditional models because these models predict
      continually accelerating (asymptotically infinite) invasion. The impossible
      predictions come from the fact that the fat-tailed kernels fitted to dispersal
      data have a quality (nondiscrete individuals and, thus, no moment-generating
      function) that never applies to data. Real organisms produce finite (and random)
      numbers of offspring; thus, an empirical moment-generating function can always be
      determined. Using an alternative method to estimate spread rates in terms of
      extreme dispersal events, we show that finite estimates can be derived for fat
      tailed kernels, and we demonstrate how variable reproduction modifies these
      rates. Whereas the traditional models define spread rate as the speed of an
      advancing front describing the expected density of individuals, our alternative
      definition for spread rate is the expected velocity for the location of the
      furthest-forward individual in the population. The asymptotic wave speed for a
      constant net reproductive rate R0 is approximated as (1/T)(piuR)/2)(1/2) m yr(
      1), where T is generation time, and u is a distance parameter (m2) of Clark et
      al.'s 2Dt model having shape parameter p = 1. From fitted dispersal kernels with
      fat tails and infinite variance, we derive finite rates of spread and a simple
      method for numerical estimation. Fitted kernels, with infinite variance, yield
      distributions of rates of spread that are asymptotically normal and, thus, have
      finite moments. Variable reproduction can profoundly affect rates of spread. By
      incorporating the variance in reproduction that results from variable life span,
      we estimate much lower rates than predicted by the standard approach, which
      assumes a constant net reproductive rate. Using basic life-history data for
      trees, we show these estimated rates to be lower than expected from previous
      analytical models and as interpreted from paleorecords of forest spread at the
      end of the Pleistocene. Our results suggest reexamination of past rates of spread
      and the potential for future response to climate change.

PMID- 18707262
TI  - Transgenerational consequences of plant responses to herbivory: an adaptive
      maternal effect?
AB  - Herbivory has many effects on plants, ranging from shifts in primary processes
      such as photosynthesis, growth, and phenology to effects on defense against
      subsequent herbivores and other species interactions. In this study, I
      investigated the effects of herbivory on seed and seedling characteristics of
      several families of wild radish (Raphanus raphanistrum) to test the hypothesis
      that herbivory may affect the quality of offspring and the resistance of
      offspring to plant parasites. Transgenerational effects of herbivory may
      represent adaptive maternal effects or factors that constrain or amplify natural
      selection on progeny. Caterpillar (Pieris rapae) herbivory to greenhouse-grown
      plants caused plants in some families to produce smaller seeds and those in other
      families to produce larger seeds compared with undamaged controls. Seed mass was
      positively associated with probability of emergence in the field. The number of
      setose trichomes, a putative plant defense, was higher in the progeny of damaged
      plants in some families and lower in the progeny of damaged plants in other
      families. In a field experiment, plant families varied in their resistance to
      several herbivores and pathogens as well as in growth rate and time to flowering.
      Seeds from damaged parent plants were more likely to become infested with a plant
      virus. Although herbivory on maternal plants did not directly affect interactions
      of offspring with other plant parasites, seed mass influenced plant resistance to
      several attackers. Thus, herbivory affected seed characters, which mediated
      interactions between plants and their parasites. Finally, irrespective of seed
      mass, herbivory on maternal plants influenced components of progeny fitness,
      which was dependent on plant family. Natural selection may act on plant responses
      to herbivory that affect seedling-parasite interactions and, ultimately, fitness.

PMID- 18707263
TI  - Constraints on the evolution of thermal sensitivity of foraging in Trichogramma:
      genetic trade-offs and plasticity in maternal selection.
AB  - Negative genetic correlation between performance at different temperatures or
      temperature-dependent mutations may promote evolution of thermal specialization
      in ectotherms. The first hypothesis implies that a selective change in
      performance at one temperature simultaneously results in change in performance at
      others, while the second implies a delay before observing such indirect
      responses. Comparison of the direction of evolution among Trichogramma lines
      selected for improvement of parasitization capacity at low, medium, or high
      temperatures indicated that a change in performance at one temperature
      concurrently resulted in opposite changes at distant temperatures. Unexpectedly,
      selection at high temperatures resulted in a decrease in adult fitness
      components, while adult performance expressed at cold temperatures simultaneously
      increased. The relationship between maternal fecundity and offspring fitness
      components varied across the thermal range. No correlation between these traits
      was present at cold or medium temperatures, but negative relationships appeared
      at high temperatures. We show that maternal selection resulting from a conflict
      between adult and offspring fitness components may have resulted in reversed
      evolution of the adult traits at the high end of the thermal range. Thus, genetic
      trade-offs in performance at different temperatures and phenotypic plasticity in
      maternal selection may constrain evolution of the thermal niche in Trichogramma.

PMID- 18707266
TI  - Interspecific competition in plants: how well do current methods answer
      fundamental questions?
AB  - Accurately quantifying and interpreting the processes and outcomes of competition
      among plants is essential for evaluating theories of plant community organization
      and evolution. We argue that many current experimental approaches to quantifying
      competitive interactions introduce size bias, which may significantly impact the
      quantitative and qualitative conclusions drawn from studies. Size bias generally
      arises when estimates of competitive ability are erroneously influenced by the
      initial size of competing individuals. We employ a series of quantitative thought
      experiments to demonstrate the potential for size bias in analysis of four
      traditional experimental designs (pairwise, replacement series, additive series,
      and response surfaces) either when only final measurements are available or when
      both initial and final measurements are collected. We distinguish three questions
      relevant to describing competitive interactions: Which species dominates? Which
      species gains? and How do species affect each other? The choice of experimental
      design and measurements greatly influences the scope of inference permitted.
      Conditions under which the latter two questions can give biased information are
      tabulated. We outline a new approach to characterizing competition that avoids
      size bias and that improves the concordance between research question and
      experimental design. The implications of the choice of size metrics used to
      quantify both the initial state and the responses of elements in interspecific
      mixtures are discussed. The relevance of size bias in competition studies with
      organisms other than plants is also discussed.

PMID- 18707267
TI  - Life-history evolution in guppies. VII. The comparative ecology of high- and low
      predation environments.
AB  - Prior research has demonstrated a strong association between the species of
      predators that co-occur with guppies and the evolution of guppy life histories.
      The evolution of these differences in life histories has been attributed to the
      higher mortality rates experienced by guppies in high-predation environments.
      Here, we evaluate whether there might be indirect effects of predation on the
      evolution of life-history patterns and whether there are environmental
      differences that are correlated with predation. To do so, we quantified features
      of the physical and chemical environment and the population biology of guppies
      from seven high- and low-predation localities. We found that high-predation
      environments tend to be larger streams with higher light levels and higher
      primary productivity, which should enhance food availability for guppies. We also
      found that guppy populations from high-predation environments have many more
      small individuals and fewer large individuals than those from low-predation
      environments, which is caused by their higher birth rates and death rates.
      Because of these differences in size distribution, guppies from high-predation
      environments have only one-fourth of the biomass per unit area, which should also
      enhance food availability for guppies in these localities. Guppies from high
      predation sites allocate more resources to reproduction, grow faster, and attain
      larger asymptotic sizes, all of which are consistent with higher levels of
      resource availability. We conclude that guppies from high-predation environments
      experience higher levels of resource availability in part because of correlated
      differences in the environment (light levels, primary productivity) and in part
      as an indirect consequence of predation (death rates and biomass density). These
      differences in resource availability can, in turn, augment the effect of predator
      induced mortality as factors that shape the evolution of guppy life-history
      patterns. We found no differences in the invertebrate communities from high- and
      low-predation localities, so we conclude that there do not appear to be
      multitrophic, indirect effects associated with these differences in predation.

PMID- 18707268
TI  - Causes and consequences of monodominance in tropical lowland forests.
AB  - Tropical canopy dominance in lowland, well-drained forests by one plant species
      is a long-standing conundrum in tropical biology. Research now shows that
      dominance is not the result of one trait or mechanism. We suggest that the
      striking dominance of Gilbertiodendron dewevrei in the Ituri Forest of
      northeastern Congo is the result of a number of traits in adult trees that
      significantly modify the understory environment, making it difficult for other
      species to regenerate there. Adults cast deep shade that reduces light levels in
      the understory of the Gilbertiodendron forest to levels significantly lower than
      in the mixed-species forest. Moreover, the monodominant forest has deep leaf
      litter that could inhibit the establishment of small-seeded species, and the leaf
      litter is slow to decompose, potentially causing the low availability of
      nitrogen. We expect that juveniles of Gilbertiodendron may have an advantage in
      this environment over other species. In general, it appears that all tropical
      monodominant species share a similar suite of traits.

PMID- 18707269
TI  - How territorial animals compete for divisible space: a learning-based model with
      unequal competitors.
AB  - It is widely assumed that aggressive behavior affects space acquisition in
      territorial species, but to date most workers have focused on competition for
      indivisible space, that is, space that cannot be divided or shared. We present a
      learning-based model that investigates the effects of aggressive interactions on
      space acquisition when unequal competitors arrive and settle in patches of
      divisible space. This model assumes that aggressive interactions act as
      punishment, in the sense that previous aggressive interactions in a given area
      reduce an individual's likelihood of returning to that area. Individually based,
      spatially explicit simulations incorporating this and other assumptions were used
      to investigate the effects of different types of aggressive interactions on the
      space use of individuals and dyads settling in divisible space. At the individual
      level, final space use was related to the amount of punishment that individuals
      inflicted on their opponents during aggressive interactions; in general, highly
      aggressive individuals acquired larger, more exclusive home ranges than less
      aggressive individuals. At the dyadic level, the division or sharing of space
      between competitors depended on both the relative and absolute punishment that
      competitors inflicted on one another during aggressive interactions. Aggressive
      interactions in which both participants strongly punished one another (e.g.,
      escalated fights) produced mutually exclusive home ranges, interactions with
      intermediate levels of punishment produced asymmetrical space use patterns
      proportional to asymmetries in punishment levels, and interactions involving
      little punishment for either participant generated large home ranges with
      extensive home range overlap. Overall, our model implies that territorial animals
      need not "win" aggressive interactions to win divisible space, that repeatedly
      "nagging" an opponent may also be a viable strategy for gaining space, and that a
      learning-based approach can account for puzzling patterns in the territorial
      literature, for example, observations of individuals who acquire space by
      initiating aggressive interactions that they never win.

PMID- 18707270
TI  - Competition of phytoplankton under fluctuating light.
AB  - Light is an essential resource for phytoplankton and fluctuates on a wide range
      of timescales. To understand how light fluctuations affect phytoplankton
      community structure and diversity, we have studied a set of simple models using a
      combination of analytical and numerical techniques. Light fluctuations can affect
      community structure when species exhibit the gleaner-opportunist trade-off
      between competitive ability and ability to reach carrying capacity quickly. Fast
      fluctuations can switch the competitive dominant from a gleaner to an
      opportunist; slow fluctuations can cause this switch and also lead to stable
      coexistence. Coexistence is easiest between species that are highly
      differentiated along the gleaner-opportunist trade-off. Our results remain
      qualitatively unchanged when more realistic light fluctuations such as daily and
      seasonal changes in irradiance and the presence of a spatial gradient in light
      are considered. Seasonal change in day length may be one of the factors driving
      the seasonal succession of phytoplankton, from opportunist species dominant under
      shorter day lengths (spring and autumn) to gleaner species dominant under longer
      day length (summer). These results illustrate how resource fluctuations can have
      an important role in structuring ecological communities.

PMID- 18707271
TI  - Dispersal, migration, and offspring retention in saturated habitats.
AB  - We examine the evolutionary stability of year-round residency in territorial
      populations, where breeding sites are a limiting resource. The model links
      individual life histories to the population-wide competition for territories and
      includes spatial variation in habitat quality as well as a potential parent
      offspring conflict over territory ownership. The general form of the model makes
      it applicable to the evolution of dispersal, migration, partial migration, and
      delayed dispersal (offspring retention). We show that migration can be
      evolutionarily stable only if year-round residency in a given area would produce
      a sink population, where mortality exceeds reproduction. If this applies to a
      fraction of the breeding habitat only, partial migration is expected to evolve.
      In the context of delayed dispersal, habitat saturation has been argued to form
      an ecological constraint on independent breeding, which favors offspring
      retention and cooperative breeding. We show that habitat saturation must be
      considered as a dynamic outcome of birth, death, and dispersal rates in the
      population, rather than an externally determined constraint. Although delayed
      dispersal often associates with intense competition for territories, life-history
      traits have direct effects on stable dispersal strategies, which can often
      override the effect of habitat saturation. As an example, high survival of
      floaters selects against delayed dispersal, even though it increases the number
      of competitors for each breeding vacancy (the "habitat saturation factor"). High
      survival of territory owners, by contrast, generally favors natal philopatry. We
      also conclude that spatial variation in habitat quality only rarely selects for
      delayed dispersal. Within a population, however, offspring retention is more
      likely in high-quality territories.

PMID- 18707272
TI  - Allee effects, invasion pinning, and species' borders.
AB  - All species' ranges are the result of successful past invasions. Thus, models of
      species' invasions and their failure can provide insight into the formation of a
      species' geographic range. Here, we study the properties of invasion models when
      a species cannot persist below a critical population density known as an "Allee
      threshold." In both spatially continuous reaction-diffusion models and spatially
      discrete coupled ordinary-differential-equation models, the Allee effect can
      cause an invasion to fail. In patchy landscapes (with dynamics described by the
      spatially discrete model), range limits caused by propagation failure (pinning)
      are stable over a wide range of parameters, whereas, in an uninterrupted habitat
      (with dynamics described by a spatially continuous model), the zero velocity
      solution is structurally unstable and thus unlikely to persist in nature. We
      derive conditions under which invasion waves are pinned in the discrete space
      model and discuss their implications for spatially complex dynamics, including
      critical phenomena, in ecological landscapes. Our results suggest caution when
      interpreting abrupt range limits as stemming either from competition between
      species or a hard environmental limit that cannot be crossed: under a wide range
      of plausible ecological conditions, species' ranges may be limited by an Allee
      effect. Several example systems appear to fit our general model.

PMID- 18707273
TI  - Linking the allee effect, sexual reproduction, and temperature-dependent sex
      determination via spatial dynamics.
AB  - We develop a spatially explicit, two-sex, individual-based model (IBM) and a
      derived spatially homogeneous model (SHM) to describe the Allee effect due to
      scarcity of mating possibilities at low population sizes or densities. The SHM,
      based on coupled difference equations, represents the first spatially homogeneous
      approach to this phenomenon, which differentiates between sexes and relies only
      on measurable population parameters. The IBM reinforces the findings of the SHM
      by adopting more realistic mate search strategies of diffusive movement and
      active search. Both models are characterized by a hyperbolic-shaped extinction
      boundary in the male-female state space, which contrasts with a linear boundary
      in one-dimensional models of the Allee effect. We examine how the position of the
      extinction boundary depends on population demography (primary sex ratio,
      reproduction and mortality probabilities) and adopted mate search strategies. The
      investigation of different phases in the IBM dynamics emphasizes the differences
      between local and global densities and shows the importance of scale when
      assessing the Allee effect. To demonstrate the potential application of our
      models, we combine the SHM and available data to predict the impact of
      environmental temperature changes on two turtle species with temperature
      dependent sex determination.

PMID- 18707274
TI  - Are plants really larger in their introduced ranges?
AB  - The "rule" that individuals of nonindigenous plant species are larger where they
      are introduced than where they are native is not borne out in detailed
      comparisons of European species introduced to California or the Carolinas and
      species from California and the Carolinas introduced to Europe. On average,
      individuals of California species are taller in California than in Europe, while
      individuals of species native to Europe do not differ between Europe and
      California. Similarly, individuals of species from the Carolinas are, on average,
      taller in the Carolinas than in Europe, while individuals of European species are
      the same height in Europe and the Carolinas or, depending on the nature of the
      statistical analysis, taller in Europe. Results for herbaceous species only are
      substantially the same. Although there is no general tendency for species to be
      taller in their introduced ranges, many species are, in fact, taller in some
      regions where they are introduced than in their native ranges. Absence of natural
      enemies in the introduced range is one hypothesis for such observations, but
      other hypotheses are possible, and the specific reasons for height differences
      must be sought case by case. The absence of a general tendency casts doubt on the
      biological control strategy of introducing sequences of phytophages, none of
      which delivers a knockout blow to a weed, with the expectation that each
      successive phytophage will force the plant to devote more resources to defense
      and fewer to traits such as increased size that make it more competitive.

PMID- 18707275
TI  - Experimental confirmation that inbreeding depression increases extinction risk in
      butterfly populations.

PMID- 18707276
TI  - Propagule size and the relative success of exotic ungulate and bird introductions
      to New Zealand.
AB  - We investigated factors affecting the success of 14 species of ungulates
      introduced to New Zealand around 1851-1926. The 11 successful species had a
      shorter maximum life span and were introduced in greater numbers than the three
      unsuccessful species. Because introduction effort was confounded with other life
      history traits, we examined whether independent introductions of the same species
      were more likely to succeed when a greater number of individuals were introduced.
      For the six species with introductions that both succeeded and failed, successful
      introductions always involved an equal or greater number of individuals than
      unsuccessful introductions of the same species. For all independent
      introductions, there was a highly significant relationship between the number of
      individuals introduced and introduction success. When data for ungulate and bird
      introductions to New Zealand were combined, a variable categorizing species as
      ungulate or bird was a highly significant predictor of introduction success,
      after variation in introduction effort was controlled. For a given number of
      individuals introduced, ungulates were much more likely to succeed than birds.

PMID- 18707277
TI  - Paleontology and the comparative method: ancestral node reconstructions versus
      observed node values.
AB  - Comparative methods are used to reconstruct ancestral node values for
      continuously varying traits. The confidence intervals (CIs) around such estimates
      may be wider than the range of tip data from which they are calculated. Without
      historical data with which to compare estimates, it is not clear whether such
      broad CIs reflect evolutionary lability or methodological imprecision. In this
      study, a fully resolved phylogeny of fossil carnivorans, in which observed
      samples are found not only at the tree tips but also along branches and at nodes,
      is used to compare observed ancestral node values with node estimates based on a
      Brownian motion model of evolution. As in previous studies, the CIs surrounding
      node estimates were wider than the range of tree tip values, but observed values
      fell well within them, reasonably close to the values predicted by comparative
      methods. Confidence intervals calculated using paleontological rate estimates
      were comparable to those calculated using only terminal taxa. This implies that
      evolution of at least some traits is conservative enough for node reconstruction
      techniques to be useful, despite their large standard errors. The Brownian motion
      model of evolutionary change was a good predictor of node values.

PMID- 18707278
TI  - Variation in plant responses to neighbors at local and regional scales.
AB  - Differences in the responses of plant species to neighbors may determine their
      distribution among contrasting environments, but no studies have compared
      variation in competitive or facilitative abilities both within and among
      environments. We determined whether the responses of plants to interspecific
      interactions varied at large scales (between environments) and small scales
      (among sites within an environment) across a tree line. We separated the effects
      of above- and belowground interactions on seedlings of grasses and trees grown in
      prairie or forest using vegetation removals at several sites. Species
      interactions generally had no significant effect on transplant survival.
      Competition reduced seedling growth by about 33%-89% in both prairie and forest
      environments. Despite the strong suppression of growth by neighbors, environment
      and species effects contributed more to variation in transplant performance than
      did neighbor removals. Responses to neighbors varied among transplant species but
      generally did not vary significantly between environments or among sites. With
      vegetation removed, grasses grew significantly faster in prairie and trees grew
      faster in forest. Thus, in the absence of neighbors, species showed distinct
      preferences for the environment in which they are most abundant. In summary, the
      responses of grasses and woody species to neighbors did not vary significantly at
      either large (between environments) or small (among sites) scales. These results
      suggest that species responses to interspecific interactions do not vary strongly
      with environment or smaller-scale site effects.

PMID- 18707279
TI  - The role of jelly coats in sperm-egg encounters, fertilization success, and
      selection on egg size in broadcast spawners.
AB  - Sperm limitation may be an important selective force influencing gamete traits
      such as egg size. The relatively inexpensive extracellular structures surrounding
      many marine invertebrate eggs might serve to enhance collision rates without the
      added cost of increasing the egg cell. However, despite decades of research, the
      effects of extracellular structures on fertilization have not been conclusively
      documented. Here, using the sea urchin Lytechinus variegatus, we remove jelly
      coats from eggs, and we quantify sperm collisions to eggs with jelly coats, eggs
      without jelly coats, and inert plastic beads. We also quantify fertilization
      success in both egg treatment groups. We find that sperm-egg collision rates
      increase as a function of sperm concentration and target size and that sperm are
      not chemotactically attracted to eggs nor to jelly coats in this species. In
      fertilization assays, the presence of the jelly coat is correlated with a
      significant but smaller-than-expected improvement in fertilization success. A
      pair of optimality models predict that, despite the large difference in the
      energetic value of egg contents and jelly material, the presence of the jelly
      coat does not diminish selection for larger egg cell size when sperm are
      limiting.

PMID- 18707280
TI  - The ecology and macroecology of mammalian home range area.
AB  - Although many studies employ allometric relationships to demonstrate possible
      dependence of various traits on body mass, the relationship between home range
      size and body mass has been perhaps the most difficult to understand. Early
      studies demonstrated that carnivorous species had larger home ranges than
      herbivorous species of similar mass. These studies also argued that scaling
      relations (e.g., slopes) of the former were steeper than those of the latter and
      explained this in terms of the distribution of food resources, which are more
      uniformly distributed for most herbivores than for carnivores. In contrast to
      these studies, we show that scaling relations of home ranges for carnivorous
      mammals do not differ significantly from those of herbivorous and omnivorous
      species and that all three exhibit slopes that are significantly steeper than
      predicted on the basis of energetic requirements. We also demonstrate that home
      range size is constrained to fit within a polygonal constraint space bounded by
      lines representing energetic and/or biophysical limitations, which suggests that
      the log-linear relationship between home range area and mass may not be the
      appropriate function to compare against the energetically predicted slopes of
      0.75 or 1.0. It remains unclear, however, why the slope of the relationship
      between home range area and body mass, whether based on raw data or on constraint
      lines, always exceeds that predicted by the energetic needs hypothesis.

PMID- 18707281
TI  - High species diversity in fleshy-fruited tropical understory plants.
AB  - Key innovations may increase the number of taxa in a clade that possesses the
      proposed innovation in comparison to its sister group that lacks the trait
      through either increased speciation or reduced extinction rates. Comparing sister
      clades across several independent lineages provides statistical support that the
      trait has increased species diversity. Previous studies have indicated that there
      may not be a relationship between biotic dispersal and higher species diversity,
      but only a few of these studies specified habit, habitat, or type of disperser.
      No previous study has specified all of the above parameters and used a
      phylogenetic approach. This article examines species diversity in numerous
      lineages of tropical understory plants with small, fleshy, bird-dispersed fruits
      for which a reliable estimate of phylogenetic relationships is available. Clades
      with fleshy fruits are significantly more diverse than sister clades with dry
      fruits.

PMID- 18707282
TI  - Effects of enrichment on simple aquatic food webs.
AB  - Simple models, based on Lotka-Volterra types of interactions between predator and
      prey, predict that enrichment will have a destabilizing effect on populations and
      that equilibrium population densities will change at the top trophic level and
      every second level below. We experimentally tested these predictions in three
      aquatic food web configurations subjected to either high or low nutrient
      additions. The results were structured by viewing the systems as either food
      chains or webs and showed that trophic level biomass increased with enrichment,
      which contradicts food chain theory. However, within each trophic level, food web
      configuration affected the extent to which different functional groups responded
      to enrichment. By dividing trophic levels into functional groups, based on
      vulnerability to consumption, we were able to identify significant effects that
      were obscured when systems were viewed as food chains. The results support the
      prediction that invulnerable prey may stabilize trophic-level dynamics by
      replacing other, more vulnerable prey. Furthermore, the vulnerable prey, such as
      Daphnia and edible algae, responded as predicted by the paradox of enrichment
      hypothesis; that is, variability in population density increased with enrichment.
      Hence, by describing ecosystems as a matrix of food web interactions, and by
      recognizing the interplay between interspecific competition and predation, a more
      complete description of the ecosystem function was obtained compared to when
      species were placed into distinct trophic levels.

PMID- 18707283
TI  - The Moran effect and phase synchronization in complex spatial community dynamics.

PMID- 18707288
TI  - The strength of phenotypic selection in natural populations.
AB  - How strong is phenotypic selection on quantitative traits in the wild? We
      reviewed the literature from 1984 through 1997 for studies that estimated the
      strength of linear and quadratic selection in terms of standardized selection
      gradients or differentials on natural variation in quantitative traits for field
      populations. We tabulated 63 published studies of 62 species that reported over
      2,500 estimates of linear or quadratic selection. More than 80% of the estimates
      were for morphological traits; there is very little data for behavioral or
      physiological traits. Most published selection studies were unreplicated and had
      sample sizes below 135 individuals, resulting in low statistical power to detect
      selection of the magnitude typically reported for natural populations. The
      absolute values of linear selection gradients |beta| were exponentially
      distributed with an overall median of 0.16, suggesting that strong directional
      selection was uncommon. The values of |beta| for selection on morphological and
      on life-history/phenological traits were significantly different: on average,
      selection on morphology was stronger than selection on phenology/life history.
      Similarly, the values of |beta| for selection via aspects of survival, fecundity,
      and mating success were significantly different: on average, selection on mating
      success was stronger than on survival. Comparisons of estimated linear selection
      gradients and differentials suggest that indirect components of phenotypic
      selection were usually modest relative to direct components. The absolute values
      of quadratic selection gradients |gamma| were exponentially distributed with an
      overall median of only 0.10, suggesting that quadratic selection is typically
      quite weak. The distribution of gamma values was symmetric about 0, providing no
      evidence that stabilizing selection is stronger or more common than disruptive
      selection in nature.

PMID- 18707289
TI  - Terrestrial trophic cascades: how much do they trickle?
AB  - Although more consensus is now emerging on the magnitude and frequency of
      cascading trophic effects in aquatic communities, the debate over their
      terrestrial counterparts continues. We used meta-analysis to analyze field
      experiments on trophic cascades in terrestrial arthropod-dominated food webs to
      evaluate the overall magnitude of trophic cascades and conditions affecting their
      occurrence and strength. We found extensive support for the presence of trophic
      cascades in terrestrial communities. In the majority of experiments, predator
      removal led to increased densities of herbivorous insects and higher levels of
      plant damage. Cascades in which removing predators led to decreased herbivory
      also were detected but were less frequent and weaker, suggesting a predominantly
      three-trophic-level behavior of arthropod-dominated terrestrial food webs.
      Despite the clear evidence that cascades often decreased plant damage, residual
      effects of predation produced either no or only minimal changes in overall plant
      biomass. Agricultural systems and natural communities exhibited similarly strong
      effects of predation on herbivore abundance. However, resulting effects on plant
      damage and community-wide effects of trophic cascades on plant biomass usually
      were highly variable, and only in the managed agricultural systems did predators
      occasionally have strong indirect effects on plant biomass. Our meta-analysis
      suggests that the effects of trophic cascades on the biomass of primary producers
      are weaker in terrestrial than aquatic food webs.

PMID- 18707290
TI  - The relative roles of adaptation and phylogeny in determination of larval traits
      in diversifying anuran lineages.
AB  - I measured phenotypic traits important to the fitness of larval anurans to assess
      the relative roles of ancestral trait value and selective regime in determining
      present-day phenotypes. The positions of 14 species from three taxonomic families
      and three different habitats in a phenotypic space defined by 19 traits provided
      measures of taxonomic and ecological similarity. The distribution of phenotypic
      distances among species revealed that neither taxonomy nor habitat overwhelmingly
      determined phenotype. There appear to be multiple ways in which anurans can
      exploit pond types. However, the direction of phenotypic movement was not random
      from one species to the next. Independent contrasts revealed significant
      correlations in the evolution of traits that were consistent among lineages.
      These correlations reflected well-known trade-offs that result from functional
      relationships among the constituent traits. Although there is no simple pattern
      in the distribution of mean phenotypes across environments and lineages, the
      pattern of the evolutionary trajectories that created that distribution is
      consistent with a predictive theory of multivariate evolution.

PMID- 18707291
TI  - Competition along a spatial gradient of resource supply: a microbial experimental
      model.
AB  - In a set of laboratory experiments, we examined competition for phosphorus
      between algae and bacteria under various carbon:phosphorus (C:P) supply ratios in
      spatially homogeneous and heterogeneous microcosms. Experimental results were
      compared to those predicted by theoretical models of resource competition. In the
      spatially heterogeneous microcosm, algae that were inferior competitors for P
      persisted in vessels with high local C:P supply ratios that would cause exclusion
      in the spatially homogeneous microcosms. Resource competition theory, adapted to
      this system, provided a starting point for explaining these results. Spatial
      structure can enhance local diversity because locally inferior competitors are
      transported from source habitats into sink habitats where they would otherwise be
      excluded. Such local sources were determined by their resource supply ratios.
      These results verify the hypothesis that spatial processes enhance local
      diversity when a system of local habitats is divided into sources and sinks in
      such a way that each persisting species has at least one source within the
      system. However, existing theoretical models did not accurately predict
      distributions of competitor abundance within this experimental system.

PMID- 18707292
TI  - Age and experience affect female choice in the guppy (Poecilia reticulata).
AB  - Female choices of males, and how these choices are influenced by ecological and
      social factors, have been studied extensively. However, little is known about the
      effects of age and breeding experience on female mating decisions. We used video
      techniques to examine female mate choice in guppies based on the area of
      carotenoid (orange) pigmentation on the body. Females were presented with paired
      images of males, one ornamented and the other plain. Visual preference for each
      male was measured. Age-related changes in the criteria of choice were examined by
      comparing the responses of the same mature but sexually inexperienced 6-mo-old
      and 12-mo-old females. Effects of breeding experience on female choice were
      examined by comparing mate preferences of 12-mo-old female virgins with their
      preferences after they had mated and produced a brood. Female preferences for
      ornamented males with large areas of carotenoid pigment changed with age but not
      with mating experience. Six-month-old virgin females preferred ornamented males,
      whereas 12-mo-old virgin and postpartum females did not differentiate between
      males based on orange coloration. The results are discussed in light of life
      history theory and have important implications for studies of sexual selection as
      well as for the design of mate-choice studies.

PMID- 18707293
TI  - Dimensional approaches to scaling experimental ecosystems: designing mousetraps
      to catch elephants.
AB  - Enclosed experimental ecosystems (mesocosms) are small relative to their natural
      counterparts, are typically operated for short durations relative to the
      timescales of a number of important ecological processes, and also often have
      reduced biological and physical complexity relative to nature. These reductions
      in time, space, and complexity scales have been cited as sources of unrealistic
      ecological behavior within mesocosms and raise questions about extrapolating
      results from mesocosms to nature. Dimensional analysis, a technique widely used
      by engineers to create scale models, uses compensatory distortion as a means of
      maintaining dynamic similarity in properties and relationships of interest.
      Although biological parameters are generally less controllable than physical
      ones, a variety of dimensional approaches can be taken to maintain such key
      ecological properties as effective habitat size, environmental variability,
      vertical and horizontal gradients, interactions among habitats, and control of
      experimental artifacts. To date, application of dimensional approaches to
      mesocosm design has been largely intuitive and idiosyncratic. We argue that a
      more explicit, systematic, and quantitative approach will increase realism and
      may also provide a critical means of developing, testing, and advancing our
      understanding of scaling relationships in nature.

PMID- 18707294
TI  - Sex ratio represents a unique context for selection on attractive traits:
      consequences for the evolution of sexual dimorphism.
AB  - We explored the idea that sex ratio represents a unique context for selection on
      attractive traits by manipulating sex ratio and pollinator abundance in
      experimental populations of a gender-dimorphic wild strawberry Fragaria
      virginiana. We found that increasing the frequency of functional males (the
      pollen-bearing morph) increased the frequency of pollen-collecting syrphid flies
      in the pollinator assemblage, decreased pollinator visitation to less preferred
      morph (females), and decreased the degree of pollen limitation of females.
      Moreover, sex ratio influenced the strength of selection on petal size through
      female fitness but did not alter the strength of selection through male fitness
      components, suggesting that sex ratio can alter the gender bias of selection on
      an attractive trait. This study of context-dependent selection has important
      implications for the evolution of sexual dimorphism in attractive traits. First,
      it suggests that only certain conditions generate male-biased selection and,
      thus, could lead to selection-driven male-biased petal size dimorphism. Second,
      it suggests that flexible pollinator foraging may be an important mechanism by
      which sex ratio influences selection on attractive traits. Finally, it implies
      that variation in sex ratio could limit the evolution of sexual dimorphism and/or
      could maintain genetic variation in attractive traits.

PMID- 18707295
TI  - Why do large mothers produce large offspring? Theory and a test.
AB  - To explain the general tendency of large mothers to produce large offspring, we
      developed two models in which either the rate at which each single offspring
      extracts resources from the mother or the rate at which the mother supplies
      resources to all the offspring is limited (terminal- or upper-stream-limitation
      on resource transport, respectively). We also reanalyzed the data of Erythronium
      japonicum to test the models. The terminal-stream-limitation model predicted that
      the optimal offspring size that maximizes the fitness of the mother increases
      with an increase in the maximum rate of resource extraction by each single
      offspring. Thus, large mothers produce large offspring if the maximum resource
      extraction rate is high in those mothers. The upper-stream-limitation model
      predicted that the optimal offspring size decreases with an increase in the
      maximum rate of resource supply by the mother to all the offspring. In E.
      japonicum, the maximum growth rate of a seed was independent of the number of
      seeds of a plant, suggesting that the resource extraction rate is limited at the
      individual seed level. The maximum growth rate was high in large plants and had a
      strong positive effect on final seed mass. Thus, the results were consistent with
      the terminal-stream-limitation model.

PMID- 18707297
TI  - Evolution, science, and society.

PMID- 18707298
TI  - Foreword: evolution in the century of biology.

PMID- 18707301
TI  - The effect of density-independent mortality on the coexistence of exploitative
      competitors for renewing resources.
AB  - Many ecologists believe that higher mortality imposed on competing species
      increases the probability that they will coexist. This belief has persisted in
      spite of many theoretical counterarguments. However, few of those
      counterarguments have been based on models having explicit representation of the
      resources for which competition is occurring. This article analyzes a series of
      consumer-resource models of competition for nutritionally substitutable renewable
      resources and determines the range of relative resource requirements that allow
      coexistence. In most cases, if consumers are initially efficient at reducing
      resource densities, increasing density-independent mortality widens the range of
      resource requirements of the consumers that allow coexistence, provided the
      increase in mortality is not too great. The coexistence-promoting effects of
      mortality occur because a very efficient consumer species usually reduces the
      diversity of the set of resources it consumes. This lessens the extent to which
      resource utilization differences between consumer species can be expressed.
      Mortality, in this case, increases the diversity of resource types, widening the
      conditions for coexistence. However, sufficiently high mortality will usually
      reduce the range of parameters allowing coexistence, in agreement with much
      previous theory. The results presented here also predict maximal diversity at
      intermediate levels of productivity. Previous empirical studies and theory are
      reviewed in light of the theory developed here.

PMID- 18707302
TI  - Is sociality driven by the costs of dispersal or the benefits of philopatry? A
      role for kin-discrimination mechanisms.
AB  - The role of ecological constraints in promoting sociality is currently much
      debated. Using a direct-fitness approach, we show this role to depend on the kin
      discrimination mechanisms underlying social interactions. Altruism cannot evolve
      under spatially based discrimination, unless ecological constraints prevent
      complete dispersal. Increasing constraints enhances both the proportion of
      philopatric (and thereby altruistic) individuals and the level of altruistic
      investments conceded in pairwise interactions. Familiarity-based discrimination,
      by contrast, allows philopatry and altruism to evolve at significant levels even
      in the absence of ecological constraints. Increasing constraints further enhances
      the proportion of philopatric (and thereby altruistic) individuals but not the
      level of altruism conceded. Ecological constraints are thus more likely to affect
      social evolution in species in which restricted cognitive abilities, large group
      size, and/or limited period of associative learning force investments to be made
      on the basis of spatial cues.

PMID- 18707303
TI  - Convergence in morphological patterns and community organization between Old and
      New World rodent guilds.
AB  - We studied morphological relationships within three guilds of gerbillid rodents
      in Israel. We found a nonrandom pattern of overdispersed means (community-wide
      character displacement) for upper incisor widths among the species in these three
      guilds. Upper tooth-row lengths, condylo-basal skull lengths, and tooth-row
      surfaces displayed similar patterns. We also studied seed-size selection by two
      well-studied gerbil species, which have previously been found to compete, in
      order to test whether specializing on husking seeds of different sizes as a
      mechanism of coexistence may underlie the morphological patterns. The seed-size
      selection experiments took place in two large aviaries with artificial lighting
      simulating full-moon nights, which is when predation risk is perceived as high.
      Seeds of different sizes (commercial seeds in one experiment and husked wheat
      particles in the other) mixed with sand were offered in trays. The larger
      Gerbillus pyramidum took significantly larger commercial seeds and marginally
      larger wheat particles than the smaller Gerbillus allenbyi. The patterns attest
      to ecomorphological convergence at the guild level; we previously demonstrated
      size structuring in several North American heteromyid rodent guilds, and we now
      report similar size structuring among Israeli gerbillid guilds. The occurrence of
      convergent community structure strongly indicates general rules governing
      ecological communities or guilds.

PMID- 18707304
TI  - Effects of foliar herbivory by insects on the fitness of Raphanus raphanistrum:
      damage can increase male fitness.
AB  - Generally, effects of herbivory on plant fitness have been measured in terms of
      female reproductive success (seed production). However, male plant fitness,
      defined as the number of seeds sired by pollen, contributes half of the genes to
      the next generation and is therefore crucial to the evolution of natural plant
      populations. This is the first study to examine effects of insect herbivory on
      both male and female plant reproductive success. Through controlled field and
      greenhouse experiments and genetic paternity analysis, we found that foliar
      damage by insects caused a range of responses by plants. In one environment,
      damaged plants had greater success as male parents than undamaged plants. Neither
      effects on pollen competitive ability nor pollinator visitation patterns could
      explain the greater siring success of these damaged plants. Success of damaged
      plants as male parents appeared to be due primarily to changes in allocation to
      flowers versus seeds after damage. Damaged plants produced more flowers early in
      the season, but not more seeds, than undamaged plants. Based on total seed
      production, male fitness measures from the first third of the season, and flower
      production, we estimated that damaged and undamaged plants had equal total
      reproductive success at the end of the season in this environment. In a second,
      richer environment, damaged and undamaged plants had equal male and female plant
      fitness, and no traits differed significantly between the treatments. Equal total
      reproductive success may not be ecologically or evolutionarily equivalent if it
      is achieved differentially through male versus female fitness. Genes from damaged
      plants dispersed through pollen may escape attack from herbivores, if such attack
      is correlated spatially from year to year.

PMID- 18707305
TI  - The effect of resource aggregation at different scales: optimal foraging behavior
      of Cotesia rubecula.
AB  - Resources can be aggregated both within and between patches. In this article, we
      examine how aggregation at these different scales influences the behavior and
      performance of foragers. We developed an optimal foraging model of the foraging
      behavior of the parasitoid wasp Cotesia rubecula parasitizing the larvae of the
      cabbage butterfly Pieris rapae. The optimal behavior was found using stochastic
      dynamic programming. The most interesting and novel result is that the effect of
      resource aggregation within and between patches depends on the degree of
      aggregation both within and between patches as well as on the local host density
      in the occupied patch, but lifetime reproductive success depends only on
      aggregation within patches. Our findings have profound implications for the way
      in which we measure heterogeneity at different scales and model the response of
      organisms to spatial heterogeneity.

PMID- 18707306
TI  - Can females gain extra paternal investment by mating with multiple males? A game
      theoretic approach.
AB  - Although females may require only one mating to become inseminated, many female
      animals engage in costly mating with multiple males. One potential benefit of
      polyandrous mating is gaining parental investment from multiple males. We
      developed two game theoretic models to explore this possibility. Our first model
      showed that male care of multiple females' offspring evolves when male help
      substantially increases offspring fitness, future mating opportunity is limited,
      and group size is small. In our second model, we assumed that males invest in the
      offspring of former mates and evaluated the fitness consequences of female
      monogamous and polyandrous mating strategies. Females benefit only from limited
      polyandry, that is, mating with several males. Polyandry is discouraged because
      females must share male investment with other polyandrous females, and paternal
      care is likely to experience diminishing returns. Females may enhance their
      access to male investment by competing with rival females and monopolizing
      investment, however. The results support the argument that females can gain
      paternal investment by mating with several males in small social groups (e.g.,
      dunnocks Prunella modularis). The results do not support the argument that
      females can gain paternal investment from pronounced multiple mating in large
      social groups, however, as observed in many primate species.

PMID- 18707307
TI  - Complex mate searching in the satin bowerbird Ptilonorhynchus violaceus.
AB  - Mate-choice studies typically focus on male traits affecting female mating
      decisions, but few studies seek to identify the behavioral rules females use when
      searching for mates. Current models suggest that females may either directly
      compare a set of males ("pooled comparison") or compare each male to an internal
      standard ("sequential-search rule") when judging the suitability of potential
      mates. Models also differ in other specific aspects, such as the predicted number
      of sampling bouts initiated and the tendency of females to return to males after
      previous visits. We monitored 63 female satin bowerbirds, Ptilonorhynchus
      violaceus, during mate sampling to reconstruct their search patterns. We found
      that females typically sampled several males and returned to the most attractive
      male for mating: a behavior consistent with the pooled-comparison tactic.
      Females, however, varied in the number of males sampled; some visited only one
      male before mating. We found that this variation can be explained by differences
      among females in the number of mates, the date mate searching is initiated, and
      long-term experience with males. Further, females were observed to initiate two
      distinct sampling bouts, with the rejection of most of their potential mates
      occurring before the start of the second sampling bout. This suggests that the
      choices of potential mates are narrowed prior to the second sampling bout and
      that the later visits may function to reconsider preliminary decisions made
      during the first sampling bout or to resolve decisions concerning the remaining
      potential mates. Our results indicate that mate searching is a complex process in
      which females use multiple sampling bouts to find suitable mates and in which
      several different factors influence their search behavior.

PMID- 18707308
TI  - A dynamic model of size-dependent reproductive effort in a sequential
      hermaphrodite: a counterexample to Williams's conjecture.
AB  - In 1966, G. C. Williams showed that for iteroparous organisms, the level of
      reproductive effort that maximizes fitness is that which balances the marginal
      gains through current reproduction against the marginal losses to expected future
      reproduction. When, over an organism's lifetime, the value of future reproduction
      declines relative to the value of current reproduction, the level of effort
      allocated to current reproduction should always increase with increasing age.
      Conversely, when the value of future reproduction increases relative to the value
      of current reproduction, the level of effort allocated to current reproduction
      should decrease or remain at zero. While this latter pattern occurs commonly in
      species that exhibit a delayed age at first reproduction, it may also occur
      following an initial period of reproduction in some sex-changing organisms that
      experience a dramatic increase in reproductive potential as they grow larger.
      Indeed, this schedule of reproductive effort is predicted by models of "early"
      sex change; however, these models may arrive at this result incidentally because
      they consider only two reproductive states: on and off. In order to examine the
      schedule of reproductive effort in greater detail in a system where the potential
      reproductive rate increases sharply, we adapt the logic and methods of time
      dependent dynamic-programming models to develop a size-dependent model of
      reproductive effort for an example species that experiences a dramatic increase
      in reproductive potential at large sizes: the bluehead wrasse, Thalassoma
      bifasciatum. Our model shows that the optimal level of reproductive effort will
      decline with increasing size or age when increases to the residual reproductive
      value outpace the increases to current reproductive potential. This result
      confirms the logic of Williams's analysis of optimal life histories, while
      offering a realistic counterexample to his conjecture of ever-increasing
      allocation to current reproduction.

PMID- 18707309
TI  - Fuzzy chaos: reduced chaos in the combined dynamics of several independently
      chaotic populations.

PMID- 18707311
TI  - Fitness components and ecological risk of transgenic release: a model using
      Japanese medaka (Oryzias latipes).
AB  - Any release of transgenic organisms into nature is a concern because ecological
      relationships between genetically engineered organisms and other organisms
      (including their wild-type conspecifics) are unknown. To address this concern, we
      developed a method to evaluate risk in which we input estimates of fitness
      parameters from a founder population into a recurrence model to predict changes
      in transgene frequency after a simulated transgenic release. With this method, we
      grouped various aspects of an organism's life cycle into six net fitness
      components: juvenile viability, adult viability, age at sexual maturity, female
      fecundity, male fertility, and mating advantage. We estimated these components
      for wild-type and transgenic individuals using the fish, Japanese medaka (Oryzias
      latipes). We generalized our model's predictions using various combinations of
      fitness component values in addition to our experimentally derived estimates. Our
      model predicted that, for a wide range of parameter values, transgenes could
      spread in populations despite high juvenile viability costs if transgenes also
      have sufficiently high positive effects on other fitness components. Sensitivity
      analyses indicated that transgene effects on age at sexual maturity should have
      the greatest impact on transgene frequency, followed by juvenile viability,
      mating advantage, female fecundity, and male fertility, with changes in adult
      viability, resulting in the least impact.

PMID- 18707312
TI  - Contrasting effects of plant richness and composition on insect communities: a
      field experiment.
AB  - We experimentally separated the effects of two components of plant diversity
      plant species richness and plant functional group richness-on insect communities.
      Plant species richness and plant functional group richness had contrasting
      effects on insect abundances, a result we attributed to three factors. First,
      lower insect abundances at higher plant functional group richness were explained
      by a sampling effect, which was caused by the increasing likelihood that one low
      quality group, C4 grasses, would be present and reduce average insect abundances
      by 25%. Second, plant biomass, which was positively related to plant functional
      group richness, had a strong, positive effect on insect abundances. Third, a
      positive effect of plant species richness on insect abundances may have been
      caused by greater availability of alternate plant resources or greater
      vegetational structure. In addition, a greater diversity of insect species, whose
      individual abundances were often unaffected by changes in plant species richness,
      may have generated higher total community abundances. After controlling for the
      strong, positive influence of insect abundance on insect diversity through
      rarefaction, insect species richness increased as plant species richness and
      plant functional group richness increased. Although these variables did not
      explain a high proportion of variation individually, plant species richness and
      plant functional group richness had similar effects on insect diversity and
      opposing effects on insect abundances, and both factors may explain how the loss
      of plant diversity influences higher trophic levels.

PMID- 18707313
TI  - Variation in response to artificial selection for light sensitivity in guppies
      (Poecilia reticulata).
AB  - We performed artificial selection on the visual system in guppies (Poecilia
      reticulata), using the optomotor reaction threshold as the selection criterion.
      Two lines were selected for increased sensitivity to blue light, two were
      selected for increased sensitivity to red light, and two were unselected
      controls. There was significant response to selection in all four selected lines
      and significant heritability for sensitivity. An examination of the spectral
      sensitivity function showed that the form of the response differed between the
      red and blue lines and among the red lines. Such divergence is likely because
      there are many different mechanisms allowing response to selection for spectral
      sensitivity. Diverse mechanisms allow a divergent response by different
      populations to the same selective pressures. Such a mechanism can promote
      diversity in vision and visual signals, and any multicomponent system where
      different components can respond to the same selective regime.

PMID- 18707314
TI  - The competition-colonization trade-off is dead; long live the competition
      colonization trade-off.
AB  - When applied at the individual patch level, the classic competition-colonization
      models of species coexistence assume that propagules of superior competitors can
      displace adults of inferior competitors (displacement competition). But if adults
      are invulnerable to displacement by propagules (as trees are to seeds), and
      propagules compete to replace adults that die for reasons independent of the
      outcome of juvenile competition (a lottery system), a competition-colonization
      trade-off alone is not able to produce coexistence. However, we show that
      coexistence is possible if patch density varies spatially, such that it becomes a
      niche axis. We also show how a dispersal-fecundity trade-off can partition
      variation in patch density. We discuss the application of these models to
      empirical systems. An important implication of communities coexisting via
      variation in patch density is that the amount of habitat loss necessarily
      interacts with the pattern of loss in affecting extinctions, invasions, and
      coexistence, in contrast to displacement competition models, for which the
      spatial pattern of loss is not important or is less important. Finally, with
      respect to mechanisms promoting coexistence, we suggest that trade-offs between
      different stages of colonization could be far more common in nature than a trade
      off between competitive ability and colonization ability.

PMID- 18707315
TI  - Effects of resource distribution on sexual selection and the cost of reproduction
      in sandgobies.
AB  - I describe the results of an experimental manipulation of resource availability
      (nest substrate) and distribution (nest size), leading to effects on the
      opportunity for sexual selection and the survival of male sandgobies
      Pomatoschistus minutus competing for these resources. This study represents one
      of few such experimental manipulations. It shows a clear-cut effect of male-male
      competition on the survival of males, and it shows temporal variation in the
      opportunity for sexual selection, suggesting that short-term assessment of sexual
      selection could be misleading. Males breeding under male-male competition for
      nest sites lived on average 18 d less than males in the high-nest-availability
      treatment. This considerable cost of reproduction probably stems from increased
      stress levels as a result of higher levels of aggression. The opportunity for
      sexual selection was high throughout the 2-mo experiment in the low-nest
      availability treatment, while in the high nest availability, it changed in a
      complex manner over the season. In the latter case, sexual selection was
      initially low but increased during midseason to values nearly as high as in the
      nest-site-limited environment and then decreased again toward the end of the
      season. Previous studies have shown that temporal variation in sexual selection
      follows variation in population density and sex ratio. This study demonstrates
      that there can be considerable temporal variation in the opportunity for sexual
      selection without changes in population parameters.

PMID- 18707316
TI  - Signaling individual identity versus quality: a model and case studies with
      ruffs, queleas, and house finches.
AB  - We develop an evolutionary model that predicts that characters selected to signal
      individual identity will have properties differing from those expected for
      indicator signals of quality. Traits signaling identity should be highly
      variable, often display polymodal distributions, not be condition dependent
      (i.e., be cheap to produce and/or maintain), not be associated with fitness
      differences, exhibit independent assortment of component characters, and often
      occur as fixed phenotypes with a high degree of genetic determination. We
      illustrate the existence of traits with precisely these attributes in the
      ornamental, conspicuously variable, and sexually dimorphic breeding plumages of
      ruff sandpipers Philomachus pugnax and red-billed queleas Quelea quelea. Although
      ruffs lek and queleas are monogamous, both species breed in high-density
      aggregations with high rates of social interactions (e.g., aggression and
      territory defense). Under these socioecological conditions, individual
      recognition based on visual cues may be unusually important. In contrast to these
      species, we also review plumage characteristics in house finches Carpodacus
      mexicanus, a nonterritorial, dispersed-breeding species in which plumage
      ornamentation is thought to signal quality. In keeping with expectations for
      quality signals, house finch plumage is relatively less variable, unimodally
      distributed, condition dependent, correlated with fitness measures, has
      positively correlated component characters, and is a plastic, environmentally
      determined trait. We briefly discuss signals of identity in other animals.

PMID- 18707317
TI  - The matrix matters: effective isolation in fragmented landscapes.
AB  - Traditional approaches to the study of fragmented landscapes invoke an island
      ocean model and assume that the nonhabitat matrix surrounding remnant patches is
      uniform. Patch isolation, a crucial parameter to the predictions of island
      biogeography and metapopulation theories, is measured by distance alone. To test
      whether the type of interpatch matrix can contribute significantly to patch
      isolation, I conducted a mark-recapture study on a butterfly community inhabiting
      meadows in a naturally patchy landscape. I used maximum likelihood to estimate
      the relative resistances of the two major matrix types (willow thicket and
      conifer forest) to butterfly movement between meadow patches. For four of the six
      butterfly taxa (subfamilies or tribes) studied, conifer was 3-12 times more
      resistant than willow. For the two remaining taxa (the most vagile and least
      vagile in the community), resistance estimates for willow and conifer were not
      significantly different, indicating that responses to matrix differ even among
      closely related species. These results suggest that the surrounding matrix can
      significantly influence the "effective isolation" of habitat patches, rendering
      them more or less isolated than simple distance or classic models would indicate.
      Modification of the matrix may provide opportunities for reducing patch isolation
      and thus the extinction risk of populations in fragmented landscapes.

PMID- 18707318
TI  - Pelagic tunicates: why gelatinous?

PMID- 18707319
TI  - Metapopulation dynamics and the quality of the matrix.
AB  - In both strictly theoretical and more applied contexts it has been historically
      assumed that metapopulations exist within a featureless, uninhabitable matrix and
      that dynamics within the matrix are unimportant. In this article, we explore the
      range of theoretical consequences that result from relaxing this assumption. We
      show, with a variety of modeling techniques, that matrix quality can be extremely
      important in determining metapopulation dynamics. A higher-quality matrix
      generally buffers against extinction. However, in some situations, an increase in
      matrix quality can generate chaotic subpopulation dynamics, where stability had
      been the rule in a lower-quality matrix. Furthermore, subpopulations acting as
      source populations in a low-quality matrix may develop metapopulation dynamics as
      the quality of the matrix increases. By forcing metapopulation dynamics on a
      formerly heterogeneous (but stable within subpopulations) population, the
      probability of simultaneous extinction of all subpopulations actually increases.
      Thus, it cannot be automatically assumed that increasing matrix quality will
      lower the probability of global extinction of a population.

PMID- 18707320
TI  - Plumage color as a composite trait: developmental and functional integration of
      sexual ornamentation.
AB  - Most studies of condition-dependent sexual ornaments have treated such ornaments
      as single traits. However, sexual ornaments are often composites of several
      components, each produced by partially independent developmental pathways.
      Depending on environmental and individual condition, components of these
      ornaments may reflect different behavioral or physiological properties of an
      individual. One of the best-known, condition-dependent ornaments is carotenoid
      based plumage coloration, which has at least four distinct components: pigment
      elaboration, patch area, pigment symmetry, and patch area symmetry. Here we
      examined fitness consequences of variation in individual components of carotenoid
      ornamentation in male house finches (Carpodacus mexicanus). Over 5 yr and several
      selection episodes, we studied variation in the plumage components in a large
      sample (n = 498) of males from a Montana population. The ornament components were
      partially independent of each other and had distinct fitness consequences.
      Selection for higher fecundity favored an increase in redness of coloration and a
      decrease in pigment asymmetry and patch area asymmetry but did not act on patch
      area itself. In contrast, viability selection favored larger and more symmetrical
      ornamental patches but did not act on pigment elaboration. Developmental and
      functional interrelationships among individual components of ornamentation
      strongly differed between house finch populations. Distinct patterns of selection
      on individual components of condition-dependent ornaments, combined with
      partially independent development of components, should favor the evolution of
      composite sexual traits whose components reliably reflect condition across a wide
      array of environments.

PMID- 18707321
TI  - The demographic basis of population regulation in columbian ground squirrels.
AB  - Environmental factors influence the dynamics and regulation of biological
      populations through their influences on demographic variables, but demographic
      mechanisms of population regulation have received little attention. We
      investigated the demographic basis of regulation of Columbian ground squirrel
      (Spermophilus columbianus) populations under natural and experimentally food
      supplemented conditions. Food supplementation caused substantial increases in
      population density, and population densities returned to pretreatment levels when
      the supplementation ended. Control (untreated) populations remained relatively
      stable throughout the study period (1981-1986). Because food resources regulated
      the size of the ground squirrel populations, we used life-table response
      experiment (LTRE) analyses to examine the demographic basis of changes in
      population growth rate and thus also demographic influences on population
      regulation. LTRE analyses of two food-manipulated populations revealed that
      changes in age at maturity and fertility rate of females generally made the
      largest contributions to observed changes in population growth rate. Thus, our
      results suggested that abundance of food resources regulated the size of our
      study populations through the effects of food resources on age at maturity and
      fertility rates. Our results also indicated that different demographic mechanisms
      can underlie population regulation under different environmental conditions,
      because lower juvenile survival substantially contributed to population decline,
      but in only one of the populations. Demographic analyses of experimental data,
      such as those presented here, offer a rigorous and unambiguous means to elucidate
      the demographic basis of population regulation and to help identify environmental
      factors that underlie dynamics and regulation of biological populations.

PMID- 18707322
TI  - Negligible Senescence during Reproductive Dormancy in Drosophila melanogaster.
AB  - Some endemic Drosophila overwinter in a state of adult reproductive diapause
      where egg maturation is arrested in previtellogenic stages. When maintained at
      cool temperatures, adult Drosophila melanogaster enter reproductive dormancy,
      that is, diapause or diapause-like quiescence. The ability to survive for
      extended periods is a typical feature of diapause syndromes. In adults this
      somatic persistence may involve reduced or slowed senescence. Here we assess
      whether reproductively dormant D. melanogaster age at slow rates. Adults were
      exposed to dormancy-inducing conditions for 3, 6, or 9 wk. After this period,
      demographic parameters were measured under normal conditions and compared to the
      demography of newly eclosed cohorts. The age-specific mortality rates of
      postdormancy adults were essentially identical to the mortality rates of newly
      eclosed, young flies. Postdormancy reproduction, in contrast, declined with the
      duration of the treatment; somatic survival during dormancy may tradeoff with
      later reproduction. Adults in reproductive dormancy were highly resistant to heat
      and to oxidative stress. Suppressed synthesis of juvenile hormone is known to
      regulate reproductive diapause of many insects. Treatment of dormant D.
      melanogaster with a juvenile hormone analog restored vitellogenesis, suppressed
      stress resistance, and increased demographic senescence. We conclude that D.
      melanogaster age at slow rates as part of their reproductive dormancy syndrome;
      the data do not agree with an alternative hypothesis based on heat-dependent
      "rate of living." We suggest that low temperature reduces neuroendocrine
      function, which in turn slows senescence as a function of altered stress
      response, nutrient reallocation, and metabolism.

PMID- 18707323
TI  - Impact of intraguild predation and stage structure on simple communities along a
      productivity gradient.
AB  - We analyze the consequences of intraguild predation and stage structure for the
      possible composition of a three-species community consisting of resource,
      consumer, and predator. Intraguild predation, a special case of omnivory, induces
      two major differences with traditional linear food chain models: the potential
      for the occurrence of two alternative stable equilibria at intermediate levels of
      resource productivity and the extinction of the consumer at high productivities.
      At low productivities, the consumer dominates, while at intermediate
      productivities, the predator and the consumer can coexist. The qualitative
      behavior of the model is robust against addition of an invulnerable size class
      for the consumer population and against addition of an initial, nonpredatory
      stage for the predator population, which means that the addition of stage
      structure does not change the pattern. Unless the top predator is substantially
      less efficient on the bottom resource, it tends to drive the intermediate species
      extinct over a surprisingly large range of productivities, thus making
      coexistence generally impossible. These theoretical results indicate that the
      conditions for stable food chains involving intraguild predation cannot involve
      strong competition for the bottommost resource.

PMID- 18707324
TI  - Effects of an attractive sink leading into maladaptive habitat selection.
AB  - Habitat sinks can attract dispersing animals if high mortality or breeding
      failure are difficult to detect (e.g., when due to human hunting or pollution).
      Using a simple deterministic model, we explore the dynamics of such source-sink
      systems considering three scenarios: an avoided sink, no habitat preference, and
      an attractive sink. In the second two scenarios, there is a threshold proportion
      of sink habitat above which the whole population decreases to extinction, but
      this extinction threshold varies with habitat preference and the relative
      qualities of the two habitat types. Hence, it would be necessary to know the
      habitat preferences of any species in a source-sink system to interpret data on
      population increases and declines. In the attractive sink scenario, small changes
      in the proportion of sink habitat may have disproportionate effects on the
      population persistence. Also, small changes in growth rates at the source and the
      sink severely affect the threshold and the time of extinction. For some
      combinations of demographic parameters and proportion of habitat sink, the
      decline affects the source first; thus, during some time, it will be hidden to
      population monitoring at the sink, where numbers can even increase. The
      extinction threshold is also very sensitive to the initial population sizes
      relative to carrying capacity. Attractive sinks represent a novel aspect of
      source-sink dynamics with important conservation and management implications.

PMID- 18707325
TI  - Empirical Relationships between Species Richness, Evenness, and Proportional
      Diversity.
AB  - Diversity (or biodiversity) is typically measured by a species count (richness)
      and sometimes with an evenness index; it may also be measured by a proportional
      statistic that combines both measures (e.g., Shannon-Weiner index or H'). These
      diversity measures are hypothesized to be positively and strongly correlated, but
      this null hypothesis has not been tested empirically. We used the results of
      Caswell's neutral model to generate null relationships between richness (S),
      evenness (J'), and proportional diversity (H'). We tested predictions of the null
      model against empirical relationships describing data in a literature survey and
      in four individual studies conducted across various scales. Empirical
      relationships between log S or J' and H' differed from the null model when <10
      species were tested and in plants, vertebrates, and fungi. The empirical
      relationships were similar to the null model when >10 and <100 species were
      tested and in invertebrates. If >100 species were used to estimate diversity, the
      relation between log S and H' was negative. The strongest predictive models
      included log S and J'. A path analysis indicated that log S and J' were always
      negatively related, that empirical observations could not be explained without
      including indirect effects, and that differences between the partials may
      indicate ecological effects, which suggests that S and J' act like diversity
      components or that diversity should be measured using a compound statistic.

PMID- 18707326
TI  - Starlings can categorize symmetry differences in dot displays.
AB  - Fluctuating asymmetry is an estimate of developmental stability and, in some
      cases, the asymmetry of morphological traits can reflect aspects of individual
      fitness. As asymmetry can be a marker for fitness, it has been proposed that
      organisms could use morphological asymmetry as a direct visual cue during inter-
      and intraspecific encounters. Despite some experimental evidence to support this
      prediction, the perceptual abilities of animals to detect and respond to symmetry
      differences have been largely overlooked. Studying the ability of animals to
      perceive symmetry and factors that affect this ability are crucial to assessing
      whether fluctuating asymmetry could be used as a visual cue in nature. In this
      study, we investigated the ability of wild-caught European starlings Sturnus
      vulgaris to learn to discriminate symmetry from asymmetry in random dot patterns
      through operant learning experiments. The birds did not possess a spontaneous
      preference for either symmetry or asymmetry. The birds learned a symmetry
      preference, although the learning process took longer than that previously
      reported for pigeons Columba livia and was more error prone. After being trained
      to discriminate symmetry differences in random dot patterns, birds successfully
      transferred their symmetry discrimination abilities to a set of novel stimuli
      that they had not previously seen. This indicates that starlings can form a
      mental categorization of visual stimuli on the basis of a somewhat generalized
      symmetry phenomenon. We discuss these findings in relation to the probability
      that birds use fluctuating asymmetry as a visual cue.

PMID- 18707327
TI  - On indirect genetic effects in structured populations.
AB  - Indirect genetic effects (IGEs) occur when the phenotype of an individual, and
      possibly its fitness, depends, at least in part, on the genes of its social
      partners. The effective result is that environmental sources of phenotypic
      variance can themselves evolve. Simple models have shown that IGEs can alter the
      rate and direction of evolution for traits involved in interactions. Here we
      expand the applicability of the theory of IGEs to evolution in metapopulations by
      including nonlinear interactions between individuals and population genetic
      structure. Although population subdivision alone generates some dramatic and
      nonintuitive evolutionary dynamics for interacting phenotypes, the combination of
      nonlinear interactions with subdivision reveals an even greater importance of
      IGEs. The presence of genetic structure links the evolution of interacting
      phenotypes and the traits that influence their expression ("effector traits")
      even in the absence of genetic correlations. When nonlinear social effects occur
      in subdivided populations, evolutionary response is altered and can even oppose
      the direction expected due to direct selection. Because population genetic
      structure allows for multilevel selection, we also investigate the role of IGEs
      in determining the response to individual and group selection. We find that
      nonlinear social effects can cause interference between levels of selection even
      when they act in the same direction. In some cases, interference can be so
      extreme that the actual evolutionary response to multilevel selection is opposite
      in direction to that predicted by summing selection at each level. This
      theoretical result confirms empirical data that show higher levels of selection
      cannot be ignored even when selection acts in the same direction at all levels.

PMID- 18707328
TI  - Darwin's naturalization hypothesis revisited.

PMID- 18707330
TI  - Effects of releasing maladapted individuals: a demographic-evolutionary model.
AB  - A model of the joint dynamics of change in population size N and evolution in a
      quantitative trait z, as a result of a general form of density dependence, local
      stabilizing selection, and immigration of individuals deviating from the local
      optimum, is analyzed. For weak selection and migration, a reduction in total
      equilibrium population size below the initial level without immigration, K, is
      shown to occur if the immigrants deviates more than square root of 8 = 2.83
      genetic standard deviations from the optimum and if the rate of migration m is
      sufficiently large relative to the strength of stabilizing selection s. For the
      Lotka-Volterra form of density dependence, two additional equilibria are shown to
      exist below K, provided that the strength of selection is large relative to the
      strength of density dependence. Reintroduction of an initially extinct population
      is possible if the immigrants are not too maladapted and if the genetic variance
      is sufficiently large. For a simplified version of the model corresponding to
      competition between similar species or different haplotypes, the equilibrium
      population size is always exactly at K if m < Ksz1(2) and is above K otherwise,
      which shows the importance of including recombination in the model.

PMID- 18707331
TI  - Extinction-colonization dynamics and host-plant choice in butterfly
      metapopulations.
AB  - Species living in highly fragmented landscapes often occur as metapopulations
      with frequent population turnover. Turnover rate is known to depend on ecological
      factors, such as population size and connectivity, but it may also be influenced
      by the phenotypic and genotypic composition of populations. The Glanville
      fritillary butterfly (Melitaea cinxia) in Finland uses two host-plant species
      that vary in their relative abundances among distinct habitat patches (dry
      meadows) in a large network of approximately 1,700 patches. We found no effect of
      host species use on local extinction. In contrast, population establishment was
      strongly influenced by the match between the host species composition of an empty
      habitat patch and the relative host use by larvae in previous years in the
      habitat patches that were well connected to the target patch. This "colonization
      effect" could be due to spatially variable plant acceptability or resistance or
      to spatially variable insect oviposition preference or larval performance. We
      show that spatial variation in adult oviposition preference occurs at the
      relevant spatial scale and that the other possible causes of the colonization
      effect can be discounted. We conclude that the colonization effect is generated
      by host preference influencing the movement patterns of ovipositing females.
      Migrant females with dissimilar host preferences have different perceptions of
      relative patch quality, which influences their likelihood of colonizing patches
      with particular host composition.

PMID- 18707332
TI  - Sexual imprinting and the origin of obligate brood parasitism in birds.
AB  - We discuss two pathways along which obligate brood parasitism (OBP) may evolve
      and examine some of the critical steps that must be passed by letting great tits
      Parus major be reared by blue tits Parus caeruleus in a field experiment. The
      cross-fostered chicks survived well in blue tit nests, but their local
      recruitment and reproductive success was much lower than that of controls. The
      effect was strongest when great tits grew up with siblings of the host species
      rather than with conspecific siblings in blue tit nests. The low success seemed
      to be caused by misimprinting because the cross-fostered birds behaved like blue
      tits in several aspects (species association, alarm calls, and aggressive
      response by resident females to caged intruders). Some birds of both sexes were
      apparently so strongly imprinted that they did not attract or accept a social
      mate of their own species. We conclude that imprinting may be necessary for OBP
      to evolve in birds because the parasite must be attracted to the nests of the
      host species to add eggs and thereby continue the parasitic life cycle. However,
      strong imprinting may also prevent OBP from occurring if parasitic offspring seek
      a mate from the host species.

PMID- 18707333
TI  - How predator incursions affect critical patch size: the role of the functional
      response.
AB  - Understanding the impact of habitat edges provides a key to deciphering how
      community dynamics change as functions of habitat structure and spatial scale.
      Motivated by studies of predation on bird nests in forest fragments and other
      cases of "cross-boundary subsidies," we present results from a partial
      differential equation model in which a patch-resident prey species suffers
      incidental mortality from a generalist predator species residing in the
      surrounding matrix habitat. We demonstrate that predator intrusions have the
      potential to induce critical patch size effects for the prey species, even when
      the prey's dynamics would otherwise preclude such effects. We also demonstrate
      that the existence of critical patch size effects depends on the functional
      response of the predator, with Lotka-Volterra and Type II functional responses
      generating the effect (but not Type III). We conclude by discussing how predator
      induced critical patch size effects can influence opportunities for regionwide
      persistence of the prey by altering the fraction and spatial distribution of
      meaningful patches within a metapopulation.

PMID- 18707334
TI  - Diffuse selection on resistance to deer herbivory in the ivyleaf morning glory,
      Ipomoea hederacea.
AB  - Recent work defines coevolution between plants and herbivores as pairwise when
      the pattern of selection on resistance traits and the response to selection are
      both independent of the presence or absence of other herbivores. In addition, for
      a pairwise response to selection, resistance to a focal herbivore must have the
      same genetic basis in the presence and absence of other herbivores. None of these
      conditions were satisfied for the ivyleaf morning glory, Ipomoea hederacea, and
      its insect, fungal, and mammalian natural enemies with a quantitative genetics
      field experiment. A significant negative genetic correlation exists between
      resistance to deer and generalist insect herbivory that would preclude an
      independent response to selection. In addition, resistance loci under selection
      differ depending on the composition of the natural enemy community as indicated
      by genetic correlations between deer resistances in the presence and absence of
      other natural enemies that differ substantially from 1. Finally, selection on
      deer resistance depends on the presence or absence of insects; in the presence of
      insects, greater deer resistance is favored, but in the absence of insects, deer
      resistance is effectively neutral. These results indicate that the composition of
      the natural enemy community can alter both the pattern of selection and the
      likely response to selection of resistance traits.

PMID- 18707335
TI  - Rules of thumb for conservation of metapopulations based on a stochastic winking
      patch model.
AB  - From a theoretical viewpoint, nature management basically has two options to
      prolong metapopulation persistence: decreasing local extinction probabilities and
      increasing colonization probabilities. This article focuses on those options with
      a stochastic, single-species metapopulation model. We found that for most
      combinations of local extinction probabilities and colonization probabilities,
      decreasing the former increases metapopulation extinction time more than does
      increasing the latter by the same amount. Only for relatively low colonization
      probabilities is an effort to increase these probabilities more beneficial, but
      even then, decreasing extinction probabilities does not seem much less effective.
      Furthermore, we found the following rules of thumb. First, if one focuses on
      extinction, one should preferably decrease the lowest local extinction
      probability. Only if the extinction probabilities are (almost) equal should one
      prioritize decreases in the local extinction probability of the patch with the
      best direct connections to and from other patches. Second, if one focuses on
      colonization, one should preferably increase the colonization probability between
      the patches with the lowest local extinction probability. Only if the local
      extinction probabilities are (almost) equal should one instead prioritize
      increases in the highest colonization probability (unless extinction
      probabilities and colonization probabilities are very low). The rules of thumb
      have an important common denominator: the local extinction process has a greater
      bearing on metapopulation extinction time than colonization.

PMID- 18707336
TI  - Evaluating the efficacy of entomopathogenic nematodes for the biological control
      of crop pests: a nonequilibrium approach.
AB  - The efficacy of entomopathogenic nematodes for biological control is assessed
      using deterministic models. Typically, the examination of such models involves
      stability analyses to determine the long-term persistence of control. However, in
      agricultural systems, control is often needed within a single season. Hence, the
      transient dynamics of the systems were assessed under specific, short-term
      control scenarios using stage-structured models. Analyses suggest that preemptive
      application may be the optimum strategy if nematode mortality rates are low;
      applying before pest invasion can result in greater control than applying
      afterward. In addition, repeated applications will suppress a pest, providing the
      application rate exceeds a threshold. However, the period between applications
      affects control success, so the economic injury level of the crop and the life
      history of the pest should be evaluated before deciding the strategy. In all
      scenarios, the most important parameter influencing control is the transmission
      rate. These findings are applicable to more traditional biological control agents
      (e.g., microparasites and parasitoids), and we recommend the approach adopted
      here when considering their practical use. It is concluded that it is essential
      to consider the specific crop and pest characteristics and the definition of
      control success before selecting the appropriate control strategy.

PMID- 18707337
TI  - Ecological biogeography of southern ocean islands: the importance of considering
      spatial issues.
AB  - Understanding patterns of among-island variation in species richness has long
      been an important question in ecology and biogeography. However, despite the
      clear spatial nature of the data used for such investigations, the spatial
      distribution of the different sampled locations is rarely explicitly considered,
      which may be critical for statistical and biological reasons. In a recent study,
      Chown et al. (1998) investigated the relationships between species richness of
      different indigenous and introduced taxonomic groups and a variety of variables
      characterizing Southern Ocean islands, and here, we use these data to address
      spatial issues. As predicted, we found spatial autocorrelation in species
      richness for terrestrial taxa with high dispersal ability or for terrestrial taxa
      that had time to disperse locally (introduced land birds and indigenous taxa) but
      not for taxa that had low opportunity to disperse to nearby islands (introduced
      plants, insects, and mammals), which suggests that colonization from nearby
      islands has played an important role in shaping present-day patterns of among
      island variation in species richness. Interestingly, in several cases, the
      estimated effect of variables changed when spatial covariance was incorporated.
      Moreover, the absence of autocorrelation of some variables allowed us to confirm
      some important results of Chown et al. (1998), notably those involving the
      potential impact of human presence on the biodiversity of these islands. Overall,
      our results illustrate the importance of considering spatial structures in
      ecological studies. This is notably the case when dispersal processes can be
      expected to explain some of the observed patterns.

PMID- 18707338
TI  - The effects of density, spatial pattern, and competitive symmetry on size
      variation in simulated plant populations.
AB  - Patterns of size inequality in crowded plant populations are often taken to be
      indicative of the degree of size asymmetry of competition, but recent research
      suggests that some of the patterns attributed to size-asymmetric competition
      could be due to spatial structure. To investigate the theoretical relationships
      between plant density, spatial pattern, and competitive size asymmetry in
      determining size variation in crowded plant populations, we developed a spatially
      explicit, individual-based plant competition model based on overlapping zones of
      influence. The zone of influence of each plant is modeled as a circle, growing in
      two dimensions, and is allometrically related to plant biomass. The area of the
      circle represents resources potentially available to the plant, and plants
      compete for resources in areas in which they overlap. The size asymmetry of
      competition is reflected in the rules for dividing up the overlapping areas.
      Theoretical plant populations were grown in random and in perfectly uniform
      spatial patterns at four densities under size-asymmetric and size-symmetric
      competition. Both spatial pattern and size asymmetry contributed to size
      variation, but their relative importance varied greatly over density and over
      time. Early in stand development, spatial pattern was more important than the
      symmetry of competition in determining the degree of size variation within the
      population, but after plants grew and competition intensified, the size asymmetry
      of competition became a much more important source of size variation. Size
      variability was slightly higher at higher densities when competition was
      symmetric and plants were distributed nonuniformly in space. In a uniform spatial
      pattern, size variation increased with density only when competition was size
      asymmetric. Our results suggest that when competition is size asymmetric and
      intense, it will be more important in generating size variation than is local
      variation in density. Our results and the available data are consistent with the
      hypothesis that high levels of size inequality commonly observed within crowded
      plant populations are largely due to size-asymmetric competition, not to
      variation in local density.

PMID- 18707339
TI  - On the use of the time axis for ecological separation: diel rhythms as an
      evolutionary constraint.

PMID- 18707340
TI  - Can the evolution of plant defense lead to plant-herbivore mutualism?
AB  - Moderate rates of herbivory can enhance primary production. This hypothesis has
      led to a controversy as to whether such positive effects can result in
      mutualistic interactions between plants and herbivores. We present a model for
      the ecology and evolution of plant-herbivore systems to address this question. In
      this model, herbivores have a positive indirect effect on plants through
      recycling of a limiting nutrient. Plants can evolve but are constrained by a
      trade-off between growth and antiherbivore defense. Although evolution generally
      does not lead to optimal plant performance, our evolutionary analysis shows that,
      under certain conditions, the plant-herbivore interaction can be considered
      mutualistic. This requires in particular that herbivores efficiently recycle
      nutrients and that plant reproduction be positively correlated with primary
      production. We emphasize that two different definitions of mutualism need to be
      distinguished. A first ecological definition of mutualism is based on the short
      term response of plants to herbivore removal, whereas a second evolutionary
      definition rests on the long-term response of plants to herbivore removal,
      allowing plants to adapt to the absence of herbivores. The conditions for an
      evolutionary mutualism are more stringent than those for an ecological mutualism.
      A particularly counterintuitive result is that higher herbivore recycling
      efficiency results both in increased plant benefits and in the evolution of
      increased plant defense. Thus, antagonistic evolution occurs within a mutualistic
      interaction.

PMID- 18707341
TI  - Explaining leptokurtic movement distributions: intrapopulation variation in
      boldness and exploration.
AB  - Leptokurtic distributions of movement distances observed in field-release
      studies, in which some individuals move long distances while most remain at or
      near their release point, are a common feature of mobile animals. However,
      because leptokurtosis is predicted to be transient in homogeneous populations,
      persistent leptokurtosis suggests a population heterogeneity. We found evidence
      for a heterogeneity that may generate persistent leptokurtosis. We tested
      individuals of the Trinidad killifish Rivulus hartii for boldness in a tank test
      and released them back into their native stream. Boldness in the tank test
      predicted distance moved in the field releases, even after effects of size and
      sex were removed. Further, data from a 19-mo mark-recapture study showed that
      individual growth correlated positively with movement in a predator-threatened
      river zone where the Rivulus population is spatially fragmented and dispersal is
      likely to be a hazardous activity. In contrast, no such correlation existed in a
      predator-absent zone where the population is unfragmented. These results show
      that a behavioral trait, not discernible from body size or sex, contributes to
      dispersal and that a component of fitness of surviving "dispersers" is elevated
      above that of "stayers," a fundamental assumption or prediction of many models of
      the evolution of dispersal through hazardous habitat.

PMID- 18707342
TI  - Immune defense and host sociality: a comparative study of swallows and martins.
AB  - Sociality is associated with increased risks of parasitism, predation, and social
      competition, which may interact because social stress can reduce immunity, and
      parasitized individuals are more likely to fall prey to a predator. A mechanism
      allowing evolution of sociality in spite of high costs of parasitism is increased
      investment in antiparasite defenses. Here we show that the impact of parasites on
      host reproductive success was positively associated with the degree of sociality
      in the bird family Hirundinidae. However, the cost of parasitism in highly
      colonial species was countered by high levels of T- and B-cell immune responses.
      Investment in immune function among colonial species was particularly strong in
      nestlings, and among social species, this investment was associated with a
      relatively prolonged period of development, thereby leading to extended exposure
      to parasites. Thus, highly social species such as certain species of swallows and
      martins may cope with strong natural selection arising from parasites by heavy
      investment in immune function at the cost of a long exposure to nest parasites.

PMID- 18707343
TI  - Shared preferences by predators and females for male ornaments in swordtails.
AB  - Sexually dimorphic traits in many mate recognition systems have evolved in
      response to preexisting female biases. These biases are often quite general in
      form and are likely to be shared by predators, thereby imposing a cost on male
      trait expression. The Mexican tetra Astyanax mexicanus (Pisces: Characidae), a
      visual predator of swordtail fishes, exhibits the same visual preferences for
      male body size morphs as do females. Furthermore, tetras in populations where
      swordtails are absent prefer males with sword ornaments over males with swords
      removed. The predator preference is thus likely to have arisen prior to contact
      with fishes bearing the ornament, as has also been suggested for mating
      preferences for swords.

PMID- 18707344
TI  - What do the indices of reproductive skew measure?
AB  - Several indices of reproductive skew that quantify the degree of unequal
      partitioning of reproductive output among individuals have been proposed without
      consensus on their merits and defects. We believe that the major reason for the
      disagreement is the lack of discussion on what the population parameter of skew
      (population skew or true skew) should measure. In our view, the skew index should
      be an unbiased estimate of a population skew, and the estimated skew needs to
      satisfy the following two conditions. First, if the group size is equal and the
      distribution of potential of reproductive output (pi), which is scaled by the
      proportion of the individual's to the total group reproductive output, is also
      fixed, skew remains constant even when the total number of offspring in the group
      changes. Second, if the group size is different, skew should have intuitive
      biological meaning. Our analyses revealed that, among various indices so far
      proposed, only the skews estimated by Kokko and Lindstrom's lambda and Morisita's
      I(delta) satisfy the first condition. However, the two indices estimate different
      population parameters, thus implying different biological meanings. Morisita's
      I(delta) is a linear function of CV(2) (squared coefficient of variation) of pi,
      and lambda is a positive function of [Formula: see text] when offspring number
      follows a multinomial distribution. In the special cases where a group consists
      of discrete classes of breeders and nonbreeders, lambda behaves roughly inversely
      parallel to the absolute number of breeders, while I(delta) moves almost parallel
      to the proportion of nonbreeders. Furthermore, lambda is sensitive to the total
      proportion of reproductive output possessed by the dominants but is relatively
      less sensitive to the number of subordinates. We discussed the possible
      situations where either of the two indices will be useful.

PMID- 18707345
TI  - Sex ratio conflict and worker production in eusocial hymenoptera.
AB  - The best known of the conflicts occurring in eusocial Hymenoptera is queen-worker
      conflict over sex ratio. So far, sex ratio theory has mostly focused on optimal
      investment in the production of male versus female sexuals, neglecting the
      investment in workers. Increased investment in workers decreases immediate sexual
      productivity but increases expected future colony productivity. Thus, an
      important issue is to determine the queen's and workers' optimal investment in
      each of the three castes (workers, female sexuals, and male sexuals), taking into
      account a possible trade-off between production of female sexuals and workers
      (both castes developing from diploid female eggs). Here, we construct a simple
      and general kin selection model that allows us to calculate the evolutionarily
      stable investments in the three castes, while varying the identity of the party
      controlling resource allocation (relative investment in workers, female sexuals,
      and male sexuals). Our model shows that queens and workers favor the investment
      in workers that maximizes lifetime colony productivity of sexual males and
      females, whatever the colony kin structure. However, worker production is
      predicted to be at this optimum only if one of the two parties has complete
      control over resource allocation, a situation that is evolutionarily unstable
      because it strongly selects the other party to manipulate sex allocation in its
      favor. Queens are selected to force workers to raise all the males by limiting
      the number of eggs they lay, whereas workers should respond to egg limitation by
      raising a greater proportion of the female eggs into sexual females rather than
      workers as a means to attain a more female-biased sex allocation. This tug-of-war
      between queens and workers leads to a stable equilibrium where sex allocation is
      between the queen and worker optima and the investment in workers is below both
      parties' optimum. Our model further shows that, under most conditions, female
      larvae are in strong conflict with queens and workers over their developmental
      fate because they value their own reproduction more than that of siblings. With
      the help of our model, we also investigate how variation in queen number and
      number of matings per queen affect the level of conflict between queens, workers,
      and larvae and ultimately the allocation of resource in the three castes.
      Finally, we make predictions that allow us to test which party is in control of
      sex allocation and caste determination.

PMID- 18707346
TI  - Conflict over sex allocation drives conflict over reproductive allocation in
      perennial social insect colonies.
AB  - Queen-worker conflict in the social Hymenoptera has become a cornerstone of sex
      ratio theory. Extending that theory to conflict over life-history decisions,
      however, has proven controversial. Pamilo first proposed that queen-worker
      conflict over reproductive allocation should be important in perennial, social
      insect colonies, but Bourke and Chan have questioned the generality of that
      claim. Here, we reexamine this problem for the simplest case of a monogynous and
      monandrous hymenopteran society by relaxing assumptions of Pamilo's model. In
      populations with monomorphic sex ratios, queens and workers agree on allocation
      to growth versus reproduction. However, variation in sex allocation across
      colonies can induce queen-worker conflict over reproductive allocation; the
      former is a necessary condition for the latter. We explore how conflict over
      reproductive allocation depends on the population-wide sex ratio, the
      survivorship probabilities for existing colonies, and the likelihood of
      establishing new colonies. We then test our theory for two ant species, each with
      two years of data. We find considerable support for our contention of queen
      worker conflict over reproductive allocation and suggest how future studies
      should be structured to explore this conflict further.

PMID- 18707347
TI  - Food web laws or niche theory? Six independent empirical tests.

PMID- 18707348
TI  - Carotenoids, immunity, and sexual selection: comparing apples and oranges?

PMID- 18707349
TI  - Temperature, demography, and ectotherm fitness.

PMID- 18707351
TI  - Phenotypic selection on a heritable size trait revisited.
AB  - One of evolutionary biology's most persistent puzzles is the fact that apparent
      directional selection on a heritable trait in a natural population often does not
      produce a selection response. We tested three possible explanations for this
      problem using data on body size of more than 23,000 individuals, measured over 18
      yr, in a collared flycatcher (Ficedula albicollis) population. Using a restricted
      maximum likelihood "animal model," we found a narrow-sense heritability for
      fledgling tarsus length of [Formula: see text] SE and substantial common
      environment effects ([Formula: see text] SE). For survival to adulthood, the
      selection differential on tarsus length was [Formula: see text] SE. There was,
      however, no response to this selection over the study period. One explanation for
      the lack of response might have been that selection was associated with only the
      environmental (nonheritable) component of phenotype, but we found significant
      selection on breeding values (the heritable component). There was also no
      evidence of fluctuating selection pressures or of antagonistic selection between
      the sexes in selection pressures. Thus, in contrast to earlier investigations in
      this same population, none of the potential explanations for the absence of a
      selection response was supported; we discuss alternative hypotheses yet to be
      investigated.

PMID- 18707352
TI  - Spatial heterogeneity, source-sink dynamics, and the local coexistence of
      competing species.
AB  - Patch occupancy theory predicts that a trade-off between competition and
      dispersal should lead to regional coexistence of competing species. Empirical
      investigations, however, find local coexistence of superior and inferior
      competitors, an outcome that cannot be explained within the patch occupancy
      framework because of the decoupling of local and spatial dynamics. We develop two
      patch metapopulation models that explicitly consider the interaction between
      competition and dispersal. We show that a dispersal-competition trade-off can
      lead to local coexistence provided the inferior competitor is superior at
      colonizing empty patches as well as immigrating among occupied patches.
      Immigration from patches that the superior competitor cannot colonize rescues the
      inferior competitor from extinction in patches that both species colonize. Too
      much immigration, however, can be detrimental to coexistence. When competitive
      asymmetry between species is high, local coexistence is possible only if the
      dispersal rate of the inferior competitor occurs below a critical threshold. If
      competing species have comparable colonization abilities and the environment is
      otherwise spatially homogeneous, a superior ability to immigrate among occupied
      patches cannot prevent exclusion of the inferior competitor. If, however, biotic
      or abiotic factors create spatial heterogeneity in competitive rankings across
      the landscape, local coexistence can occur even in the absence of a dispersal
      competition trade-off. In fact, coexistence requires that the dispersal rate of
      the overall inferior competitor not exceed a critical threshold. Explicit
      consideration of how dispersal modifies local competitive interactions shifts the
      focus from the patch occupancy approach with its emphasis on extinction
      colonization dynamics to the realm of source-sink dynamics. The key to
      coexistence in this framework is spatial variance in fitness. Unlike in the patch
      occupancy framework, high rates of dispersal can undermine coexistence, and hence
      diversity, by reducing spatial variance in fitness.

PMID- 18707353
TI  - Premating isolation is determined by larval-rearing substrates in cactophilic
      Drosophila mojavensis. V. Deep geographic variation in epicuticular hydrocarbons
      among isolated populations.
AB  - Adult epicuticular hydrocarbon variation of 14 geographically isolated
      populations of cactophilic Drosophila mojavensis was assessed to further
      investigate mechanisms of sexual isolation. Hydrocarbon transfer experiments
      demonstrated that these compounds are part of the mate recognition system in this
      species. Sixteen of the 23 epicuticular hydrocarbon components studied differed
      in amounts between males and females, and 13 differed in quantity between the
      geographic regions encompassing Baja California and mainland Mexico (Sonora and
      Sinaloa). Eight hydrocarbon components, seven of which differed in quantity
      between sexes, showed significant sex-by-region interactions, indicating region
      specific sex reversals in hydrocarbon quantities. Such regional variation in
      epicuticular hydrocarbon profiles suggests that these hydrocarbon differences
      have also evolved in D. mojavensis since this species invaded mainland Sonora and
      Sinaloa from Baja California by switching host plants, in addition to a number of
      key genetic, behavioral, and life-history characters.

PMID- 18707354
TI  - Relatedness and the evolution of conspecific brood parasitism.
AB  - In conspecific brood parasitism (CBP), a parasitic female takes advantage of the
      parental care performed by a host female by laying eggs in the nest of the host.
      The host female raises the offspring of the parasitic female as well as her own.
      In species where local females are related, direct costs for the host might be
      more than compensated for by gains in inclusive fitness through increased
      reproduction of a related parasite, but the role of relatedness in CBP is
      debated. This inclusive-fitness model of parasitism, structured as a game between
      host and parasite, suggests that both females can gain inclusive fitness and that
      host-parasite relatedness can therefore facilitate the evolution of CBP. Crucial
      assumptions are that there is kin discrimination and a potential for host
      resistance to parasitism by unrelated females but close relatives are accepted.
      The cost of parasitism in terms of reduced clutch size or offspring survival for
      the host must not be large; otherwise, parasitism will reduce her inclusive
      fitness. Therefore, if these costs are high, it does not benefit a host to accept
      a parasite, even if the parasite is closely related. The secondary female may
      still have higher fitness from parasitism, but if the costs are high, she should
      parasitize an unrelated host, not a relative. This requires that the reduction in
      parasite success that a host can cause by resistance is not too large; otherwise,
      it will be better for the secondary female to parasitize an accepting related
      host or to nest solitarily. For these reasons, host-parasite relatedness is most
      likely to occur in animals where costs of being parasitized are low and host
      resistance can markedly reduce the success of an unrelated parasite. When costs
      are higher, parasitism of unrelated hosts may be better, and if host resistance
      strongly reduces parasite success, solitary breeding is preferable. In some
      cases, CBP is directly advantageous for the host, and it may sometimes evolve in
      close connection with cooperative breeding, which is also considered in the
      model. Some but not all empirical results support these ideas, and more detailed
      studies of behavior, relatedness, and reproduction of host and parasite are
      needed for critical tests.

PMID- 18707355
TI  - The effect of sex-allocation biasing on the evolution of worker policing in
      hymenopteran societies.
AB  - Mutual policing is thought to be important in conflict suppression at all levels
      of biological organization. In hymenopteran societies (bees, ants, and wasps),
      multiple mating by queens favors mutual policing of male production among workers
      (worker policing). However, worker policing of male production is proving to be
      more widespread than predicted by relatedness patterns, occurring in societies
      headed by single-mated queens in which, paradoxically, workers are more related
      to the workers' sons that they kill than the queen's sons that they spare. Here
      we develop an inclusive-fitness model to show that a second reproductive
      conflict, the conflict over sex allocation, can explain the evolution of worker
      policing contrary to relatedness predictions. Among ants, and probably other
      social Hymenoptera, workers kill males to favor their more related sisters.
      Importantly, males are killed at the larval stage, presumably because workers
      cannot determine the sex of queen-laid eggs. Sex-allocation biasing favors worker
      policing because policing removes some males (the workers' sons) at low cost at
      the egg stage rather than at higher cost at the larval stage. Our model reveals
      an important interaction between two reproductive conflicts in which the presence
      of one conflict (sex allocation) favors the suppression of the other (male
      production by workers).

PMID- 18707356
TI  - Effects of competition, predation, and dispersal on species richness at local and
      regional scales.
AB  - This study explores the consequences of predator-mediated coexistence among
      competitors for patterns of incidence and diversity at local and regional scales.
      We develop a model that draws on elements of metapopulation models of competitors
      and food chains by allowing competitors to coexist locally in the presence of
      predators but not in their absence. The model predicts that predators promote
      regional coexistence by greatly expanding the range of conditions under which two
      competitors persist at equilibrium. Predators could have positive or negative
      effects on mean local diversity within the region depending on their dispersal
      rates, those of the prey, and their effects on prey extinction rates. The
      presence of predators increased the abundance of inferior competitors, thereby
      expanding the conditions for positive relationships between local and regional
      diversity. The model also predicted positive correlations between local diversity
      of predators and prey. These predictions were supported by patterns of
      phytoplankton, zooplankton, and fish species richness among lakes. The model may
      help to resolve the apparent contrast between linear patterns of local and
      regional richness and experimental evidence for strong invasion resistance and
      rapid dispersal in zooplankton.

PMID- 18707357
TI  - Mutation, multilevel selection, and the evolution of propagule size during the
      origin of multicellularity.
AB  - Evolutionary transitions require the organization of genetic variation at two (or
      more) levels of selection so that fitness heritability may emerge at the new
      level. In this article, we consider the consequences for fitness variation and
      heritability of two of the main modes of reproduction used in multicellular
      organisms: vegetative reproduction and single-cell reproduction. We study a model
      where simple cell colonies reproduce by fragments or propagules of differing
      size, with mutations occurring during colony growth. Mutations are deleterious at
      the colony level but can be advantageous or deleterious at the cell level
      ("selfish" or "uniformly deleterious" mutants). Fragment size affects fitness in
      two ways: through a direct effect on adult group size (which in turn affects
      fitness) and by affecting the within- and between-group variances and opportunity
      for selection on mutations at the two levels. We show that the evolution of
      fragment size is determined primarily by its direct effects on group size except
      when mutations are selfish. When mutations are selfish, smaller propagule size
      may be selected, including single-cell reproduction, even though smaller
      propagule size has a direct fitness cost by virtue of producing smaller
      organisms, that is, smaller adult cell groups.

PMID- 18707358
TI  - Adaptation to the laboratory: comments on Sgro and Partridge.

PMID- 18707359
TI  - Laboratory adaptation of life history in Drosophila.

PMID- 18707360
TI  - The bamboo fire cycle hypothesis: a comment.

PMID- 18707361
TI  - On incorporating fire into our thinking about natural ecosystems:a response to
      Saha and Howe.

PMID- 18707366
TI  - The ecological genetics of speciation.
AB  - Ecological interactions and the natural selection they cause play a prominent
      causal role in biological diversification and speciation. As a discipline,
      ecological genetics integrates the two components of adaptive evolution (natural
      selection and genetic variability) to study the mechanisms of evolution.
      Ecological genetics is a fruitful approach to the study of how reproductive
      isolation can evolve under natural selection. The essence of this way of thinking
      and the ways in which it can be used to address persistent open questions in
      speciation are discussed.

PMID- 18707367
TI  - Speciation by natural and sexual selection: models and experiments.
AB  - A large number of mathematical models have been developed that show how natural
      and sexual selection can cause prezygotic isolation to evolve. This article
      attempts to unify this literature by identifying five major elements that
      determine the outcome of speciation caused by selection: a form of disruptive
      selection, a form of isolating mechanism (assortment or a mating preference), a
      way to transmit the force of disruptive selection to the isolating mechanism
      (direct selection or indirect selection), a genetic basis for increased isolation
      (a one- or two-allele mechanism), and an initial condition (high or low initial
      divergence). We show that the geographical context of speciation (allopatry vs.
      sympatry) can be viewed as a form of assortative mating. These five elements
      appear to operate largely independently of each other and can be used to make
      generalizations about when speciation is most likely to happen. This provides a
      framework for interpreting results from laboratory experiments, which are found
      to agree generally with theoretical predictions about conditions that are
      favorable to the evolution of prezygotic isolation.

PMID- 18707368
TI  - Genetic mapping in hybrid zones.
AB  - Recent advances in genetic mapping methodologies make it feasible to localize
      quantitative trait loci (QTL) that contribute to adaptation and speciation.
      However, it has not been possible to employ these methods in many wild species
      because of difficulties associated with creating and propagating recombinant
      populations of sufficient size for QTL mapping. Natural hybrid zones contain
      recombinant individuals resulting from many generations of hybridization and thus
      offer a potential solution to these problems. For studies of speciation, hybrid
      zones offer the possibility of mapping QTL simultaneously with assessments of
      their effects on assortative mating, hybrid fitness, and interspecific gene flow.
      Here, we explore the problems and prospects associated with genetic map building
      and QTL analyses in natural hybrid zones by analyzing correlations among markers
      of known genomic location in four hybrid zones between the wild sunflower species
      Helianthus annuus and Helianthus petiolaris. Results indicate that mapping in
      hybrid zones presents many challenges. These include overlap in the strength of
      marker correlations between linked and unlinked markers, unevenness in marker
      frequencies along linkages, and heterogeneity in the relationship between marker
      distances and correlations. All make it difficult to accurately group and order
      markers or to estimate the distances between them. These problems can be
      ameliorated by sampling strategies that maximize the difference in linkage
      disequilibria between linked and unlinked markers and that minimize differences
      in frequencies among markers or QTL. In addition, studies that employ a
      previously determined molecular marker map for gene localization have a greater
      likelihood of success than those that rely on the hybrid zone data for both map
      construction and QTL analyses.

PMID- 18707369
TI  - Genetics of floral traits influencing reproductive isolation between Aquilegia
      formosa and Aquilegia pubescens.
AB  - Abstract: Reproductive isolation between Aquilegia formosa and Aquilegia
      pubescens is influenced by differences in their flowers through their effects on
      pollinator visitation and pollen transfer. Here, we investigate the genetic basis
      of floral characters differentiating these species. We found that in addition to
      the effects of flower orientation and the length of nectar spurs previously
      described, other characters such as flower color or odor affect hawkmoth
      visitation. Repeatability of measurements in an F2 population ranged from 0.53 to
      0.83 among five floral traits, indicating that using the means of multiple
      measures per plant will substantially increase the power of a quantitative trait
      locus (QTL) analysis. Integration of floral traits was indicated by significant
      correlations among traits in an F2 population. In a separate F2 population we
      found that QTL for different floral traits were often closely associated,
      indicating that linkage or pleiotropy cause at least some of this integration. In
      addition, we found QTL for all floral traits examined. Because Aquilegia species
      are largely interfertile and vary extensively in both floral morphology and
      ecology, they offer the opportunity for QTL studies of a wide range of characters
      affecting reproductive isolation.

PMID- 18707370
TI  - Divergence of mate recognition behavior and its consequences for genetic
      architectures of speciation.
AB  - The divergence of premating behavior and morphology plays a primary role in
      speciation, and an understanding of the genetic architectures of these phenotypes
      is essential for the evaluation of models of the speciation process. However, our
      empirical knowledge of the genetics underlying speciation-related traits remains
      limited. In this article, we argue that a dissection of specific aspects of the
      genetic architecture of such traits in a comparative context can allow us to rule
      out some mechanisms of divergence. We discuss these ideas with reference to our
      investigation of intersexual communication behaviors involved in mate recognition
      in the Hawaiian cricket genus Laupala. Different species of Laupala sing
      distinctively and show species-specific acoustic preferences. We focus on the
      sister species Laupala paranigra and Laupala kohalensis, characterized by
      differences in these classic courtship phenotypes. We discuss our preliminary
      results on the directionality of effect of substituted alleles underlying these
      species differences. We then discuss these results in the context of historical
      inference, a necessary perspective for testing the genomic predictions made by
      theories of speciation that focus on evolution of mate recognition systems.

PMID- 18707371
TI  - The genetic architecture of ecological specialization: correlated gene effects on
      host use and habitat choice in pea aphids.
AB  - Genetic correlations among phenotypic characters result when two traits are
      influenced by the same genes or sets of genes. By reducing the degree to which
      traits in two environments can evolve independently (e.g., Lande 1979; Via and
      Lande 1985), such correlations are likely to play a central role in both the
      evolution of ecological specialization and in its link to speciation. For
      example, negative genetic correlations between fitness traits in different
      environments (i.e., genetic trade-offs) are thought to influence the evolution of
      specialization, while positive genetic correlations between performance and
      characters influencing assortative mating can accelerate the evolution of
      reproductive isolation between ecologically specialized populations. We first
      discuss how the genetic architecture of a suite of traits may affect the
      evolutionary role of genetic correlations among them and review how the
      mechanisms of correlations can be analyzed using quantitative trait locus (QTL)
      mapping. We then consider the implications of such data for understanding the
      evolution of specialization and its link to speciation. We illustrate this
      approach with a QTL analysis of key characters in two races of pea aphids that
      are highly specialized on different host plants and partially reproductively
      isolated. Our results suggest that antagonism among QTL effects on performance in
      the two environments leads to a genetic trade-off in this system. We also found
      evidence for parallel QTL effects on host-plant acceptance and fecundity on the
      accepted host, which could produce assortative mating. These results suggest that
      the genetic architecture of traits associated with host use may have played a
      central role in the evolution of specialization and reproductive isolation in pea
      aphids.

PMID- 18707372
TI  - The genetics of reproductive isolation: a retrospective and prospective look with
      comments on ground crickets.
AB  - An intriguing aspect of the current renaissance in investigations of the genetics
      of reproductive isolation is that it has been dominated by studies that resemble
      work done in the 1930s, 1940s, and 1950s. The dominant model organism
      (Drosophila), research approaches, and traits of interest (sterility and
      inviability of hybrids) all harken back to this earlier era. Herein, we explore
      the factors that led to a rebirth of interest in the genetics of reproductive
      isolation and to the adoption of the approaches of an earlier generation of
      biologists. At the same time, we appeal for more intensive investigations of
      traits that reproductively isolate closely related species, inclusion of a
      greater range of organisms in studies of reproductive isolation, and focus on a
      broader range of questions surrounding speciation. We end with a description of
      ongoing quantitative trait loci (QTL) studies of conspecific sperm precedence in
      the ground crickets Allonemobius fasciatus and Allonemobius socius. We have found
      several QTL with large effects on variance in patterns of sperm utilization in
      backcross females. Moreover, some QTL have an antagonistic effect on conspecific
      sperm, a finding that lends support to the hypothesis that rapid evolution of
      conspecific sperm precedence is a by-product of sexual conflict.

PMID- 18707375
TI  - Geographic song discrimination in relation to dispersal distances in song
      sparrows.
AB  - Whether geographic variation in signals actually affects communication between
      individuals depends on whether discriminable differences in signals occur over
      distances that individuals move in their lifetimes. We measure the ability of
      song sparrows (Melospiza melodia) to discriminate foreign from local songs using
      foreign songs recorded at a series of increasing distances and compare the
      results with previous measurements of dispersal distances. We test discrimination
      in males using playback of songs on territories and measuring approach and in
      females using playback to estradiol-treated captives and measuring courtship
      display. Females fail to discriminate against foreign songs recorded at 18 km but
      do discriminate against foreign songs recorded at 34, 68, 135, and 540 km. Males
      fail to discriminate against foreign songs recorded at 18, 34, 68, 135, and 270
      km but do discriminate against foreign songs from 540 km. Females are more
      discriminating, but even they do not discriminate at a distance three times the
      root-mean-square dispersal distance, as estimated from mtDNA variation. We
      suggest that female preference for local songs benefits females not because it
      allows them to reject foreign males but because accurate production of local song
      serves as a test of song-learning ability.

PMID- 18707376
TI  - Population dynamics and mutualism: functional responses of benefits and costs.
AB  - We develop an approach for studying population dynamics resulting from mutualism
      by employing functional responses based on density-dependent benefits and costs.
      These functional responses express how the population growth rate of a mutualist
      is modified by the density of its partner. We present several possible
      dependencies of gross benefits and costs, and hence net effects, to a mutualist
      as functions of the density of its partner. Net effects to mutualists are likely
      a monotonically saturating or unimodal function of the density of their partner.
      We show that fundamental differences in the growth, limitation, and dynamics of a
      population can occur when net effects to that population change linearly,
      unimodally, or in a saturating fashion. We use the mutualism between senita
      cactus and its pollinating seed-eating moth as an example to show the influence
      of different benefit and cost functional responses on population dynamics and
      stability of mutualisms. We investigated two mechanisms that may alter this
      mutualism's functional responses: distribution of eggs among flowers and fruit
      abortion. Differences in how benefits and costs vary with density can alter the
      stability of this mutualism. In particular, fruit abortion may allow for a stable
      equilibrium where none could otherwise exist.

PMID- 18707377
TI  - How do sinking phytoplankton species manage to persist?
AB  - Phytoplankton require light for photosynthesis. Yet, most phytoplankton species
      are heavier than water and therefore sink. How can these sinking species persist?
      Somehow, the answer should lie in the turbulent motion that redisperses sinking
      phytoplankton over the vertical water column. Here, we show, using a reaction
      advection-diffusion equation of light-limited phytoplankton, that there is a
      turbulence window sustaining sinking phytoplankton species in deep waters. If
      turbulent diffusion is too high, phytoplankton are mixed to great depths, and the
      depth-averaged light conditions are too low to allow net positive population
      growth. Conversely, if turbulent diffusion is too low, sinking phytoplankton
      populations end up at the ocean floor and succumb in the dark. At intermediate
      levels of turbulent diffusion, however, phytoplankton populations can outgrow
      both mixing rates and sinking rates. In this way, the reproducing population as a
      whole can maintain a position in the well-lit zone near the top of the water
      column, even if all individuals within the population have a tendency to sink.
      This theory unites earlier classic results by Sverdrup and Riley as well as our
      own recent findings and provides a new conceptual framework for the understanding
      of phytoplankton dynamics under the influence of mixing processes.

PMID- 18707378
TI  - Character displacement in giant rhinoceros beetles.
AB  - I quantitatively analyzed male morphology of two closely related rhinoceros
      beetles species (Chalcosoma caucasus F. and Chalcosoma atlas L.) in 12 allopatric
      and seven sympatric locations throughout Southeast Asia. The qualitative features
      and the magnitude of intraspecific variation of each species were unaltered
      between allopatric and sympatric locations. Across allopatric locations, body
      size, horn size, dimorphic dimension, and genitalia size nearly completely
      overlapped between C. caucasus and C. atlas. Yet, in all sympatric locations, the
      differences between the two species in these characters were highly significant.
      While the enlarged difference between the two species in body size in sympatry
      could be attributed to habitat differentiation, that in genitalia size far
      exceeded what was expected from the general body-size displacement. These results
      indicate that morphological character displacement in sympatry was most complete
      in sexual organs. This may account for the process of existing species conserving
      themselves as integrated units by avoiding interspecific competition and
      enhancing reproductive isolation.

PMID- 18707379
TI  - Costs of phenotypic plasticity.
AB  - Phenotypically plastic organisms display alternative phenotypes in different
      environments. It is widely appreciated that possessing alternative phenotypes can
      affect fitness. However, some investigators have suggested that simply carrying
      the ability to be plastic could also affect fitness. Evolutionary models suggest
      that high costs of plasticity could constrain the evolution of optimal
      phenotypes. However, costs (and limits) of plasticity are primarily hypothetical.
      Little empirical evidence exists to show that increased plasticity leads to
      reduced growth and development, leads to increased developmental instability, or
      limits the ability of organisms to produce more extreme phenotypes. I used half
      sib families of larval wood frogs (Rana sylvatica) reared in outdoor mesocosms to
      examine how tadpoles altered behavioral, morphological, and life-historical
      traits in response to larval dragonfly predators (Anax longipes). The predators
      induced lower activity and the development of relatively large tails and small
      bodies in wood frogs. As a result, wood frogs experienced reduced growth and
      development. I then examined whether tadpole sibships with higher plasticity
      experienced fitness costs (above and beyond the costs of expressing a particular
      phenotype) and whether they were limited in producing extreme phenotypes. Fitness
      effects of plasticity were widespread. Depending on the trait examined and the
      environment experienced, increased plasticity had either positive effects,
      negative effects, or no effects on tadpole mass, development, and survivorship. I
      found no relationship between increased plasticity and greater developmental
      instability. There was also no evidence that sibships with increased plasticity
      produced less extreme phenotypes; the most extreme trait states were always
      produced by the most plastic genotypes. This work suggests that costs of
      plasticity may be pervasive in nature and may substantially impact the evolution
      of optimal phenotypes in organisms that live in heterogeneous environments.

PMID- 18707380
TI  - Traffic dynamics of the leaf-cutting ant, Atta cephalotes.
AB  - Colonies of Atta cephalotes (Myrmicinae: Formicidae) construct cleared paths
      between their nest and the vegetation sources at which they harvest leaf tissue.
      Here, we employ ideas from traffic engineering to study streams of laden and
      unladen ants on these paths. The relationship between average traffic speed and
      the concentration of workers on the road surface follows a relationship similar
      to what is expected by analogy to fluid dynamics. Although the traffic is
      composed of eusocial organisms with a common interest in group success, the
      coarse-grained behavior of Atta traffic displays little more coordination than a
      moving fluid. The relationship between speed and concentration implies that
      maximum flow rates (which are likely to be closely tied to colony-level rates of
      resource acquisition) occur at a relatively high concentration that keeps
      individual speeds well below their "free flow" maximum. We predict that this
      optimal concentration will characterize peak traffic throughout a trail network,
      and we propose a simple behavioral mechanism that would allow trails to be
      cleared to the correct width to provide the optimal concentration. Collisions
      (including encounters for antennation) are common in leaf-cutting ant traffic
      because traffic is not segregated into unidirectional streams. Nonetheless, we
      find a counterintuitive suggestion that flow rates (with concentration
      differences statistically removed) are higher when traffic is near a 50:50 mix of
      outbound and returning ants than when it contains majority flows in a single
      direction. Mixed-direction traffic may help disperse laden ants with reduced
      agility, thereby preventing inhomogeneities in the traffic stream that could clog
      the trail.

PMID- 18707381
TI  - Species richness and altitude: a comparison between null models and interpolated
      plant species richness along the Himalayan altitudinal gradient, Nepal.
AB  - We compare different null models for species richness patterns in the Nepalese
      Himalayas, the largest altitudinal gradient in the world. Species richness is
      estimated by interpolation of presences between the extreme recorded altitudinal
      ranges. The number of species in 100-m altitudinal bands increases steeply with
      altitude until 1,500 m above sea level. Between 1,500 and 2,500 m, little change
      in the number of species is observed, but above this altitude, a decrease in
      species richness is evident. We simulate different null models to investigate the
      effect of hard boundaries and an assumed linear relationship between species
      richness and altitude. We also stimulate the effect of interpolation when
      incomplete sampling is assumed. Some modifications on earlier simulations are
      presented. We demonstrate that all three factors in combination may explain the
      observed pattern in species richness. Estimating species richness by
      interpolating species presence between maximum and minimum altitudes creates an
      artificially steep decrease in species richness toward the ends of the gradient.
      The addition of hard boundaries and an underlying linear trend in species
      richness is needed to simulate the observed broad pattern in species richness
      along altitude in the Nepalese Himalayas.

PMID- 18707382
TI  - Testing a simple rule for dominance in resource competition.
AB  - Competition for limiting resources long has been considered an important factor
      generating community structure. A minimal model of resource competition predicts
      that the species that reduces the limiting resource R to the lowest level
      ([Formula: see text]) will exclude its competitors. Whether this "[Formula: see
      text] rule" is robust to violations of model assumptions remains largely unknown.
      I conducted a competition experiment with four species of bacterivorous protists
      in laboratory microcosms and predicted the outcome from each species' [Formula:
      see text] value. I also examined how the outcome of competition, species
      abundances, and the effect of protists on bacterial density varied with
      productivity. Microcosms were unstirred batch cultures containing a variety of
      bacteria, challenging the robustness of the simplest competition models. Protists
      with low [Formula: see text] values were less affected by competition, although
      competing protists often coexisted. The values of [Formula: see text] can predict
      competitive dominance, even in the absence of competitive exclusion. Other model
      predictions were less robust. Contrary to expectation, densities of grazed
      bacteria increased with productivity, and the effect of some protists on
      bacterial density did not vary with productivity. Bacterial heterogeneity may
      account for deviations from model predictions. Further experiments should examine
      the conditions under which simple rules can be expected to identify dominant
      species.

PMID- 18707383
TI  - Dispersal: risk spreading versus local adaptation.
AB  - I investigate how risk spreading in stochastic environments and adaptation to
      permanent properties of local habitats interplay in the simultaneous evolution of
      dispersal and habitat specialization. In a simple two-patch model, I find many
      types of locally evolutionarily stable attractors of dispersal and of a trait
      involved in habitat specialization, including a single habitat specialist and a
      coalition of two specialists with low dispersal, a generalist with high
      dispersal, and several types of dispersal polymorphisms. In general, only one
      attractor is a global evolutionarily stable strategy (ESS). In addition to the
      ESS analysis, I also present some examples of the dynamics of evolution that
      exhibit adaptive diversification by evolutionary branching.

PMID- 18707384
TI  - Playing by different rules: the evolution of virulence in sterilizing pathogens.
AB  - We investigate the evolution of virulence of pathogens that reduce their hosts'
      fitness primarily by affecting host fecundity. We show that, under many
      conditions, such sterilizing pathogens evolve high rather than intermediate
      levels of virulence, and this pushes the pathogen population and sometimes the
      host population toward extinction. We also show that spatial population structure
      can reverse this evolutionary result and allow the persistence of intermediate
      virulence pathogens. Thus, spatial population structure may be vital to the
      persistence of sterilizing pathogens in nature.

PMID- 18707385
TI  - Ecological specialization and susceptibility to disturbance: conjectures and
      refutations.
AB  - Niche breadth of species has been hypothesized to be associated with species'
      responses to disturbance. Disturbance is usually believed to affect specialists
      negatively, while generalists are believed to benefit from disturbance; we call
      this the "specialization-disturbance" hypothesis. We also propose an associated
      hypothesis (the "specialization-asymmetry-disturbance" hypothesis) under which
      both specialization and asymmetry of interactions would explain species'
      responses to disturbance. We test these hypotheses using data from a plant
      pollinator system that has been grazed by cattle (i.e., a biological disturbance)
      in southern Argentina. We quantified specialization in species interactions,
      specialization of interaction partners, and species' responses to disturbance. We
      found no relationship between degree of specialization and a species' response to
      disturbance. We also found that plant-pollinator interactions tend to be
      asymmetric in this system; there was no relationship between the degree of
      specialization of a given species and the degree of specialization of its
      interaction partners. However, asymmetry of interactions did not explain the
      variability in species' responses to disturbance. Thus, both hypotheses are
      rejected by our data. Possible reasons include failure to assess crucial
      resources, substantial direct effects of disturbance, inaccurate measures of
      specialization, difficulty detecting highly nonlinear relationships, and
      limitations of a nonexperimental approach. Or, in fact, there may be no
      relationship between specialization and response to disturbance.

PMID- 18707386
TI  - Artificial evolution of life history and behavior.
AB  - We present an individual-based model that uses artificial evolution to predict
      fit behavior and life-history traits on the basis of environmental data and
      organism physiology. Our main purpose is to investigate whether artificial
      evolution is a suitable tool for studying life history and behavior of real
      biological organisms. The evolutionary adaptation is founded on a genetic
      algorithm that searches for improved solutions to the traits under scrutiny. From
      the genetic algorithm's "genetic code," behavior is determined using an
      artificial neural network. The marine planktivorous fish Muller's pearlside
      (Maurolicus muelleri) is used as the model organism because of the broad
      knowledge of its behavior and life history, by which the model's performance is
      evaluated. The model adapts three traits: habitat choice, energy allocation, and
      spawning strategy. We present one simulation with, and one without, stochastic
      juvenile survival. Spawning pattern, longevity, and energy allocation are the
      life-history traits most affected by stochastic juvenile survival. Predicted
      behavior is in good agreement with field observations and with previous modeling
      results, validating the usefulness of the presented model in particular and
      artificial evolution in ecological modeling in general. The advantages,
      possibilities, and limitations of this modeling approach are further discussed.

PMID- 18707387
TI  - Understanding reversals in the relative strength of sexual selection on males and
      females: a role for sperm competition?
AB  - Sperm competition affects sexual selection intensity on males, but models suggest
      it cannot affect the relative intensity of sexual selection on males compared to
      females. However, if sperm competition depresses the payoff for male multiple
      mating, it could affect the relative intensity of sexual selection and even cause
      sexual selection to be more intense on females than males (reversal of typical
      pattern). To evaluate how sperm competition, energy availability, and parental
      investment affect the intensity of sexual selection on each sex, I constructed a
      simulation model using the relationship between fecundity and number of mates to
      estimate sexual selection gradients. Unlike earlier models, I include a trade-off
      between paternal investment and sperm competition ability. The amount of energy
      available for reproduction affects the sexual selection gradient for each sex.
      Reversals in the sex experiencing stronger sexual selection do occur when
      additional paternal investment reduces a male's ability to compete for
      fertilizations within females. The shape of the distribution of mates for each
      sex (determined by mate competition) is also important. Output from the model is
      qualitatively similar to empirical data from insects with paternal investment.
      This model challenges previous thinking about the role of sperm competition in
      sex-role reversal.

PMID- 18707388
TI  - The evolution of parasite virulence, superinfection, and host resistance.
AB  - We analyze the evolutionary consequences of host resistance (the ability to
      decrease the probability of being infected by parasites) for the evolution of
      parasite virulence (the deleterious effect of a parasite on its host). When only
      single infections occur, host resistance does not affect the evolution of
      parasite virulence. However, when superinfections occur, resistance tends to
      decrease the evolutionarily stable (ES) level of parasite virulence. We first
      study a simple model in which the host does not coevolve with the parasite (i.e.,
      the frequency of resistant hosts is independent of the parasite). We show that a
      higher proportion of resistant host decreases the ES level of parasite virulence.
      Higher levels of the efficiency of host resistance, however, do not always
      decrease the ES parasite virulence. The implications of these results for
      virulence management (evolutionary consequences of public health policies) are
      discussed. Second, we analyze the case where host resistance is allowed to
      coevolve with parasite virulence using the classical gene-for-gene (GFG) model of
      host-parasite interaction. It is shown that GFG coevolution leads to lower
      parasite virulence (in comparison with a fully susceptible host population). The
      model clarifies and relates the different components of the cost of parasitism:
      infectivity (ability to infect the host) and virulence (deleterious effect) in an
      evolutionary perspective.

PMID- 18707389
TI  - Three-player social parasitism games: implications for resource defense and group
      formation.
AB  - Abstract: Individuals that produce resources are often exploited by several
      individuals; such exploitation may or may not be tolerated. We modeled the
      decision of a resource owner to accept one scrounger (the "satellite") and of
      both of these to accept being joined by another (the "floater"). In general,
      satellites tolerated floaters when competition between them was low, while owners
      tolerated satellites when facilitation between satellite and floater was high.
      When floaters were likely to find resources without joining, owners were more
      likely to resist satellites. In some cases, Nash equilibria were also mutually
      beneficial for two of the three individuals. Our model makes the counterintuitive
      prediction that mutually beneficial coalitions between satellites and floaters
      can only arise when the net benefits arising from the other's presence are low.
      When facilitation between satellites and floaters is high, satellites and owners
      may form mutually beneficial groups and groups with division of labor, or
      alternatively, owners may benefit from encouraging floaters to join. Finally, our
      model suggests there must be differences in competitive ability or some benefit
      of familiarity for owners to tolerate satellites but not floaters. We discuss
      empirical evidence for these and other predictions of the model.

PMID- 18707390
TI  - Sexual conflict about parental care: the role of reserves.
AB  - Parental care often increases the survival of offspring, but it is costly to
      parents. Because of this trade-off, a sexual conflict over care arises. The
      solution to this conflict depends on the interactions between the male and female
      parents, the behavior of other animals in the population, and the individual
      differences within a sex. We take an integrated approach and develop a state
      dependent dynamic game model of parental care. The model investigates a single
      breeding season in which the animals can breed several times. Each parent's
      decision about whether to care for the brood or desert depends on its own energy
      reserves, its mate's reserves, and the time in the season. We develop a fully
      consistent solution in which the behavior of an animal is the best given the
      behavior of its mate and of all other animals in the population. The model
      predicts that females may strategically reduce their own reserves so as to
      "force" their mate to provide care. We investigate how the energy costs of caring
      and searching for a mate, values of care (how the probability of offspring
      survival depends on the pattern of care), and population sex ratio influence the
      pattern of care over the breeding season.

PMID- 18707391
TI  - Parasite-driven extinction in spatially explicit host-parasite systems.
AB  - General host-parasite theory suggests that parasites may be implicated in the
      extinction of their hosts by causing instability that leads to increased risk of
      stochastic extinction. In contrast, spatially explicit models suggest that the
      parasite may directly drive the host population to extinction. Here we examine
      the ecological characteristics of host-parasite interactions that favor parasite
      driven host extinction. Pair approximations and simulations show that parasites
      only drive their hosts to extinction when they significantly reduce host
      reproduction. As a matter of interest, parasites that have a relatively small
      effect on host death rate are more likely to cause host extinction. Parasite
      driven host extinction occurs at any population size, whereas extinction caused
      by stochastic effects is less likely to occur in large host populations.
      Populations may therefore be under threat from parasites that stop host
      reproduction, and this type of parasite may prove to be the most effective
      biological pesticide.

PMID- 18707395
TI  - 2001 Sewall Wright Award: Ilkka A. Hanski.

PMID- 18707398
TI  - Comparing classical community models: theoretical consequences for patterns of
      diversity.
AB  - Abstract: Mechanisms proposed to explain the maintenance of species diversity
      within ecological communities of sessile organisms include niche differentiation
      mediated by competitive trade-offs, frequency dependence resulting from species
      specific pests, recruitment limitation due to local dispersal, and a speciation
      extinction dynamic equilibrium mediated by stochasticity (drift). While each of
      these processes, and more, have been shown to act in particular communities, much
      remains to be learned about their relative importance in shaping community-level
      patterns. We used a spatially-explicit, individual-based model to assess the
      effects of each of these processes on species richness, relative abundance, and
      spatial patterns such as the species-area curve. Our model communities had an
      order-of-magnitude more individuals than any previous such study, and we also
      developed a finite-size scaling analysis to infer the large-scale properties of
      these systems in order to establish the generality of our conclusions across
      system sizes. As expected, each mechanism can promote diversity. We found some
      qualitative differences in community patterns across communities in which
      different combinations of these mechanisms operate. Species-area curves follow a
      power law with short-range dispersal and a logarithmic law with global dispersal.
      Relative-abundance distributions are more even for systems with competitive
      differences and trade-offs than for those in which all species are competitively
      equivalent, and they are most even when frequency dependence (even if weak) is
      present. Overall, however, communities in which different processes operated
      showed surprisingly similar patterns, which suggests that the form of community
      level patterns cannot in general be used to distinguish among mechanisms
      maintaining diversity there. Nevertheless, parameterization of models such as
      these from field data on the strengths of the different mechanisms could yield
      insight into their relative roles in diversity maintenance in any given
      community.

PMID- 18707399
TI  - Grassland-herbivore interactions: how do grazers coexist?
AB  - We develop a new approach to modeling grazing systems that links foraging
      characteristics (intake and digestive constraints) with resource dynamics via the
      probability of encounter with different grass heights. Three complementary models
      are presented: the generation of a grass height structure through selective
      grazing; investigating the conditions for consumer coexistence; and, using a
      simplified resource structure, the consequences for consumer abundance. The main
      finding is that coexistence between grazers differing in body size is possible if
      a single-resource type becomes differentiated in its height structure. Large
      grazers can facilitate food availability for smaller species but with the latter
      being competitively dominant. The relative preference given to different resource
      partitions is important in determining the nature of population interactions.
      Large-body and small-body grazer populations can interact through competitive,
      parasitic, commensalist, or amensalist relationships, depending on the way they
      partition the resource as well as their relative populations and the dynamics of
      resource renewal. The models provide new concepts of multispecies carrying
      capacity (stock equilibrium) in grazed systems with implications for conservation
      and management. We conclude that consumer species are not substitutable;
      therefore, the use of rangeland management concepts such as "livestock units" may
      be inappropriate.

PMID- 18707400
TI  - Patchy reaction-diffusion and population abundance: the relative importance of
      habitat amount and arrangement.
AB  - A discrete reaction-diffusion model was used to estimate long-term equilibrium
      populations of a hypothetical species inhabiting patchy landscapes to examine the
      relative importance of habitat amount and arrangement in explaining population
      size. When examined over a broad range of habitat amounts and arrangements,
      population size was largely determined by a pure amount effect (proportion of
      habitat in the landscape accounted for >96% of the total variation compared to
      <1% for the arrangement main effect). However, population response deviated from
      a pure amount effect as coverage was reduced below 30%-50%. That deviation
      coincided with a persistence threshold as indicated by a rapid decline in the
      probability of landscapes supporting viable populations. When we partitioned
      experimental landscapes into sets of "above" and "below" persistence threshold,
      habitat arrangement became an important factor in explaining population size
      below threshold conditions. Regression analysis on below-threshold landscapes
      using explicit measures of landscape structure (after removing the covariation
      with habitat amount) indicated that arrangement variables accounted for 33%-39%
      of the variation in population size, compared to 27%-49% for habitat amount.
      Thus, habitat arrangement effects became important when species persistence
      became uncertain due to dispersal mortality.

PMID- 18707401
TI  - Deterministic limits to stochastic spatial models of natural enemies.
AB  - Stochastic spatial models are becoming an increasingly popular tool for
      understanding ecological and epidemiological problems. However, due to the
      complexities inherent in such models, it has been difficult to obtain any
      analytical insights. Here, we consider individual-based, stochastic models of
      both the continuous-time Lotka-Volterra system and the discrete-time Nicholson
      Bailey model. The stability of these two stochastic models of natural enemies is
      assessed by constructing moment equations. The inclusion of these moments, which
      mimic the effects of spatial aggregation, can produce either stabilizing or
      destabilizing influences on the population dynamics. Throughout, the theoretical
      results are compared to numerical models for the full distribution of
      populations, as well as stochastic simulations.

PMID- 18707402
TI  - Group size and direct fitness in social queues.
AB  - We explore the effects of group size on the direct reproductive success of
      subordinate helpers in eusocial animals where only a single, dominant individual
      reproduces at one time. Helpers can reproduce directly if they inherit dominance,
      but when dominance is age based, an individual born into a larger group has a
      longer wait to inherit. We show that this disincentive to help can potentially be
      offset by increased productivity, increased life span, and insurance-based
      benefits for helpers if they survive to inherit dominance in larger groups. We
      analyze a field experiment in which group size was manipulated in the hover wasp
      Liostenogaster flavolineata. Productivity increased linearly with group size,
      larger groups were less likely to fail, and dominants in larger groups may have
      lived longer. Combined with the probability of inheriting dominance, these
      effects led overall to a negative correlation between group size and expected
      direct fitness, mainly because group size decreased during our study period, so
      that helpers could not expect to inherit as large a group as they started queuing
      in. Our analysis suggests that the relationship between group size and
      productivity plays a central role in determining the fitness consequences of
      helping.

PMID- 18707404
TI  - Foraging-predation risk trade-offs, habitat selection, and the coexistence of
      competitors.

PMID- 18707403
TI  - Individual covariation in life-history traits: seeing the trees despite the
      forest.
AB  - We investigated the influence of age on survival and breeding rates in a long
      lived species Rissa tridactyla using models with individual random effects
      permitting variation and covariation in fitness components among individuals.
      Differences in survival or breeding probabilities among individuals are
      substantial, and there was positive covariation between survival and breeding
      probability; birds that were more likely to survive were also more likely to
      breed, given that they survived. The pattern of age-related variation in these
      rates detected at the individual level differed from that observed at the
      population level. Our results provided confirmation of what has been suggested by
      other investigators: within-cohort phenotypic selection can mask senescence.
      Although this phenomenon has been extensively studied in humans and captive
      animals, conclusive evidence of the discrepancy between population-level and
      individual-level patterns of age-related variation in life-history traits is
      extremely rare in wild animal populations. Evolutionary studies of the influence
      of age on life-history traits should use approaches differentiating population
      level from the genuine influence of age: only the latter is relevant to theories
      of life-history evolution. The development of models permitting access to
      individual variation in fitness is a promising advance for the study of
      senescence and evolutionary processes.

PMID- 18707408
TI  - Population ecology, nonlinear dynamics, and social evolution. I. Associations
      among nonrelatives.
AB  - Using an individual-based and genetically explicit simulation model, we explore
      the evolution of sociality within a population-ecology and nonlinear-dynamics
      framework. Assuming that individual fitness is a unimodal function of group size
      and that cooperation may carry a relative fitness cost, we consider the evolution
      of one-generation breeding associations among nonrelatives. We explore how
      parameters such as the intrinsic rate of growth and group and global carrying
      capacities may influence social evolution and how social evolution may, in turn,
      influence and be influenced by emerging group-level and population-wide dynamics.
      We find that group living and cooperation evolve under a wide range of parameter
      values, even when cooperation is costly and the interactions can be defined as
      altruistic. Greater levels of cooperation, however, did evolve when cooperation
      carried a low or no relative fitness cost. Larger group carrying capacities
      allowed the evolution of larger groups but also resulted in lower cooperative
      tendencies. When the intrinsic rate of growth was not too small and control of
      the global population size was density dependent, the evolution of large
      cooperative tendencies resulted in dynamically unstable groups and populations.
      These results are consistent with the existence and typical group sizes of
      organisms ranging from the pleometrotic ants to the colonial birds and the global
      population outbreaks and crashes characteristic of organisms such as the
      migratory locusts and the tree-killing bark beetles.

PMID- 18707409
TI  - Patchy populations in stochastic environments: critical number of patches for
      persistence.
AB  - We introduce a model for the dynamics of a patchy population in a stochastic
      environment and derive a criterion for its persistence. This criterion is based
      on the geometric mean (GM) through time of the spatial-arithmetic mean of growth
      rates. For the population to persist, the GM has to be >/=1. The GM increases
      with the number of patches (because the sampling error is reduced) and decreases
      with both the variance and the spatial covariance of growth rates. We derive
      analytical expressions for the minimum number of patches (and the maximum
      harvesting rate) required for the persistence of the population. As the magnitude
      of environmental fluctuations increases, the number of patches required for
      persistence increases, and the fraction of individuals that can be harvested
      decreases. The novelty of our approach is that we focus on Malthusian local
      population dynamics with high dispersal and strong environmental variability from
      year to year. Unlike previous models of patchy populations that assume an
      infinite number of patches, we focus specifically on the effect that the number
      of patches has on population persistence. Our work is therefore directly relevant
      to patchily distributed organisms that are restricted to a small number of
      habitat patches.

PMID- 18707410
TI  - Species-area curves, diversity indices, and species abundance distributions: a
      multifractal analysis.
AB  - Although fractals have been applied in ecology for some time, multifractals have,
      in contrast, received little attention. In this article, we apply multifractals
      to the species-area relationship and species abundance distributions. We
      highlight two results: first, species abundance distributions collected at
      different spatial scales may collapse into a single curve after appropriate
      renormalization, and second, the power-law form of the species-area relationship
      and the Shannon, Simpson, and Berger-Parker diversity indices belong to a family
      of equations relating the species number, species abundance, and area through the
      moments of the species abundance-probability density function. Explicit formulas
      for these diversity indices, as a function of area, are derived. Methods to
      obtain the multifractal spectra from a data set are discussed, and an example is
      shown with data on tree and shrub species collected in a 50-ha plot on Barro
      Colorado Island, Panama. Finally, we discuss the implications of the multifractal
      formalism to the relationship between species range and abundance and the
      relation between the shape of the species abundance distribution and area.

PMID- 18707411
TI  - A model of phytoplankton blooms.
AB  - A simple model that describes the dynamics of nutrient-driven phytoplankton
      blooms is presented. Apart from complicated simulation studies, very few models
      reported in the literature have taken this "bottom-up" approach. Yet, as
      discussed and justified from a theoretical standpoint, many blooms are strongly
      controlled by nutrients rather than by higher trophic levels. The analysis
      identifies an important threshold effect: a bloom will only be triggered when
      nutrients exceed a certain defined level. This threshold effect should be generic
      to both natural blooms and most simulation models. Furthermore, predictions are
      given as to how the peak of the bloom Pmax is determined by initial conditions. A
      number of counterintuitive results are found. In particular, it is shown that
      increasing initial nutrient or phytoplankton levels can act to decrease Pmax.
      Correct predictions require an understanding of such factors as the timing of the
      bloom and the period of nutrient buildup before the bloom.

PMID- 18707412
TI  - Evolutionary dynamics of prey exploitation in a metapopulation of predators.
AB  - In well-mixed populations of predators and prey, natural selection favors
      predators with high rates of prey consumption and population growth. When spatial
      structure prevents the populations from being well mixed, such predators may have
      a selective disadvantage because they do not make full use of the prey's growth
      capacity and hence produce fewer propagules. The best strategy then depends on
      the degree to which predators can monopolize the exploitation of local prey
      populations, which in turn depends on the spatial structure, the number of
      migrants, and, in particular, the stochastic nature of the colonization process.
      To analyze the evolutionary dynamics of predators in a spatially structured
      predator-prey system, we performed simulations with a metapopulation model that
      has explicit local dynamics of nonpersistent populations, keeps track of the
      number of emigrants entering the migration pool, assumes individuals within local
      populations as well as within the migration pool to be well mixed, and takes
      stochastic colonization into account. We investigated which of the predator's
      exploitation strategies are evolutionarily stable and whether these strategies
      minimize the overall density of prey, as is the case in Lotka-Volterra-type
      models of competitive exclusion. This was analyzed by pairwise invasibility plots
      based on short-term simulations and tested by long-term simulation experiments of
      competition between resident and mutant predator-types that differed in one of
      the following parameters: the prey-to-predator conversion efficiency, the per
      capita prey consumption rate, or the per capita emigration rate from local
      populations. In addition, we asked which of these three strategies are most
      likely to evolve. Our simulations showed that under selection for conversion
      efficiency the predator-prey system always goes globally extinct yet persists
      under selection for consumption or emigration rates and that the evolutionarily
      stable (ES) exploitation strategies do not maximize local population growth
      rates. The most successful exploitation strategy minimizes the overall density of
      prey but does not make it settle exactly at the minimum. The system did not
      settle at the point where the mean time to co-invasion (i.e., immigration of a
      second predator in a local prey population) equals the mean local interaction
      time (an idea borne out from studies on host exploitation strategies in host
      pathogen systems) but rather where the mean time to co-invasion was larger. The
      ES exploitation strategies represent more prudent strategies than the ones that
      minimize prey density. Finally, we show that-compared to consumption-emigration
      is a more likely target for selection to achieve prudent exploitation and that
      prudent exploitation strategies can evolve only provided the prey-to-predator
      conversion efficiency is subject to constraints.

PMID- 18707413
TI  - Trade-offs and spatial life-history strategies in classical metapopulations.
AB  - The metapopulation concept dichotomizes space into the local scale of an
      ephemeral patch and the broader scale of the persistent multipatch system. Here,
      we consider how the "best" (i.e., optimal or noninvasible) life history of
      asexually reproducing organisms might address this dichotomy along environmental
      gradients via shifts in two key trade-offs. The expansion-survival trade-off
      expresses the relation between the combined growth and propagule production rate
      and the mortality rate. The accumulation-export trade-off partitions expansion
      into a local accumulation of growth plus propagules retained within the patch and
      the potential-colonist propagules dispersed to other patches, although the
      dispersal linkages among patches are assumed to be weak (a characteristic of
      "classical" metapopulations). We identify the best life histories along gradients
      of productivity, stress, and patch extinction rates for a metapopulation with and
      without lottery or overgrowth competition, and we compare them with results for
      an isolated immortal patch. The two trade-offs interact in determining best life
      histories, but this effect is generally small, supporting the validity of studies
      addressing the trade-offs separately. The accumulation-export trade-off responds
      strongly to the three gradients, increasing export with productivity and with
      patch extinction rate when this rate is high but decreasing export with higher
      stress; the expansion-survival trade-off increases expansion with productivity
      but fails to respond to stress and patch extinction rate gradients, except when
      the other trade-off does not occur. By linking the trade-offs to life-history
      strategies (i.e., colonization, exploitation, and tolerance), we separate
      strategies from phenomenology (i.e., from export, accumulation, and survival)
      along the gradients.

PMID- 18707414
TI  - Spatial heterogeneity and irreversible vegetation change in semiarid grazing
      systems.
AB  - Recent theoretical studies have shown that spatial redistribution of surface
      water may explain the occurrence of patterns of alternating vegetated and
      degraded patches in semiarid grasslands. These results implied, however, that
      spatial redistribution processes cannot explain the collapse of production on
      coarser scales observed in these systems. We present a spatially explicit
      vegetation model to investigate possible mechanisms explaining irreversible
      vegetation collapse on coarse spatial scales. The model results indicate that the
      dynamics of vegetation on coarse scales are determined by the interaction of two
      spatial feedback processes. Loss of plant cover in a certain area results in
      increased availability of water in remaining vegetated patches through run-on of
      surface water, promoting within-patch plant production. Hence, spatial
      redistribution of surface water creates negative feedback between reduced plant
      cover and increased plant growth in remaining vegetation. Reduced plant cover,
      however, results in focusing of herbivore grazing in the remaining vegetation.
      Hence, redistribution of herbivores creates positive feedback between reduced
      plant cover and increased losses due to grazing in remaining vegetated patches,
      leading to collapse of the entire vegetation. This may explain irreversible
      vegetation shifts in semiarid grasslands on coarse spatial scales.

PMID- 18707418
TI  - Estimating density dependence from population time series using demographic
      theory and life-history data.
AB  - For populations with a density-dependent life history reproducing at discrete
      annual intervals, we analyze small or moderate fluctuations in population size
      around a stable equilibrium, which is applicable to many vertebrate populations.
      Using a life history having age at maturity alpha, with stochasticity and density
      dependence in adult recruitment and mortality, we derive a linearized
      autoregressive equation with time lags from 1 to alpha yr. Contrary to current
      interpretations, the coefficients corresponding to different time lags in the
      autoregressive dynamics are not simply measures of delayed density dependence but
      also depend on life-history parameters. The theory indicates that the total
      density dependence in a life history, D, should be defined as the negative
      elasticity of population growth rate per generation with respect to change in
      population size, [Formula: see text], where lambda is the asymptotic
      multiplicative growth rate per year, T is the generation time, and N is adult
      population size. The total density dependence in the life history, D, can be
      estimated from the sum of the autoregression coefficients. We estimate D in
      populations of seven vertebrate species for which life-history studies and
      unusually long time series of complete population censuses are available.
      Estimates of D were statistically significant and large, on the order of 1 or
      higher, indicating strong density dependence in five of the seven species. We
      also show that life history can explain the qualitative features of population
      autocorrelation functions and power spectra and observations of increasing
      empirical variance in population size with increasing length of time series.

PMID- 18707419
TI  - Developmental thresholds and the evolution of reaction norms for age and size at
      life-history transitions.
AB  - It is quite common in studies of life-history plasticity to find a negative
      relationship between the age at which various life-history transitions occur and
      the growth conditions under which individuals develop. In particular, high growth
      typically results in earlier transitions, often at a larger size. Here, we use a
      relatively general optimization model for age and size at life-history
      transitions to argue that current life-history theory cannot adequately explain
      these results. Specifically, most such theory requires key assumptions that are
      unlikely to be generally met. This suggests that some important component of the
      biology of many organisms must be missing from many of the models in life-history
      theory. We suggest that this missing component might be the phenomenon of
      developmental thresholds. There are at least two different types of developmental
      thresholds possible, and we incorporate these into our general optimality model
      to demonstrate how they can cause a negative relationship between growth
      conditions and age at a transition. If developmental thresholds are common
      throughout taxa, then this might explain the empirical results. Our model
      formulation and analysis also formalizes the popular Wilbur-Collins hypothesis
      for age and size at metamorphosis in amphibians. The results demonstrate that
      optimal combinations of age and size, and the slope of the reaction norm
      connecting them, depend on the existence and type of threshold assumed. Our
      results also provide an evolutionary framework that can be used to view the data
      and many of the proximate submodels derived from the Wilbur-Collins hypothesis.

PMID- 18707420
TI  - Pattern does not equal process: what does patch occupancy really tell us about
      metapopulation dynamics?
AB  - Patch occupancy surveys are commonly used to parameterize metapopulation models.
      If isolation predicts patch occupancy, this is generally attributed to a balance
      between distance-dependent recolonization and spatially independent extinctions.
      We investigated whether similar patterns could also be generated by a process of
      spatially correlated extinctions following a unique colonization event (analogous
      to nonequilibrium processes in island biogeography). We simulated effects of
      spatially correlated extinctions on patterns of patch occupancy among pikas
      (Ochotona princeps) at Bodie, California, using randomly located extinction disks
      to represent the likely effects of predation. Our simulations produced similar
      patterns to those cited as evidence of balanced metapopulation dynamics.
      Simulations using a variety of disk sizes and patch configurations confirmed that
      our results are potentially applicable to a broad range of species and sites.
      Analyses of the observed patterns of patch occupancy at Bodie revealed little
      evidence of rescue effects and strong evidence that most recolonizations are
      ephemeral in nature. Persistence will be overestimated if static or declining
      patterns of patch occupancy are mistakenly attributed to dynamically stable
      metapopulation processes. Consequently, simple patch occupancy surveys should not
      be considered as substitutes for detailed experimental tests of hypothesized
      population processes, particularly when conservation concerns are involved.

PMID- 18707421
TI  - Signaling health versus parasites.
AB  - The Hamilton-Zuk hypothesis, that parasite-host coevolution can maintain
      heritable variation in fitness, has inspired a very successful research program
      on sexual selection on signals of health. The immunocompetence handicap
      hypothesis was developed to provide a handicapping mechanism to stabilize the
      correlation between signals and health. In earlier articles, I showed that
      handicap signaling is a special case, not a general law that we can rely on to
      deduce relative costs across signalers of different quality at equilibrium. The
      essential requirement for reliable signaling is that higher-quality signalers are
      more efficient; they get greater marginal fitness returns from an incremental
      increase in the signal. This does not undermine the Hamilton-Zuk hypothesis or
      the immunocompetence mechanism, but it does raise doubts about a widespread
      assumption that is commonly used to test these hypotheses: that sexual selection
      on signals of health implies the choice of mates with the fewest parasites.
      Immunity and parasites might play a fundamental role in many biological signaling
      systems, but viability-indicating traits are not necessarily parasite-load
      indicating traits. Theory allows for the possibility that high-quality big
      signalers have greater health and more parasites than low-quality small signalers
      (and the data suggest that in many systems they do). This means that we cannot
      test the Hamilton-Zuk hypothesis or the immunocompetence handicap hypothesis by
      counting parasites. More generally, we cannot understand sexual selection on
      signals of health by focusing on the viability costs of signals.

PMID- 18707422
TI  - Using "travel time" data to characterize the behavior of migrating animals.
AB  - For migratory species, duration of migration, or "travel time," is often a
      critical variable in determining the cost of migration. Observed travel times are
      the result of both environmental factors such as air or water currents and the
      behavior of individuals. In an effort to distinguish among these components, I
      developed a migration model based on an advection-diffusion equation that
      characterizes population movements in terms of two biologically meaningful
      parameters: migration rate and rate of population spread. I applied the model to
      travel time data from juvenile chinook salmon (Onchorhynchus tshawytscha), which
      were tagged during their seaward migration. The tagged fish originated from three
      separate evolutionarily significant units (ESUs) as classified by the U. S.
      National Marine Fisheries Service. The model was expanded by allowing migration
      and diffusion rates to vary with fish length and river flow. Variability in
      travel times explained by these factors was strikingly similar from year to year
      within ESUs, and the migratory behavior revealed by the analysis was consistent
      with the life-history patterns that distinguish the ESUs. The approach presented
      here is easily adaptable to a wide range of migratory species and may be
      particularly useful for predicting how at-risk populations respond to variable
      conditions in regulated or otherwise disturbed migration habitats.

PMID- 18707423
TI  - General relationships between species diversity and stability in competitive
      systems.
AB  - Investigating the effect of biodiversity on the stability of ecological
      communities is complicated by the numerous ways in which models of community
      interactions can be formulated. This has led to differences in conclusions and
      interpretations of how the number of species in a community affects its
      stability. Here, we derive a simple, general relationship between the coefficient
      of variation (CV) of combined species densities and the environmentally driven
      variability in species' per capita population growth rates. For a given level of
      environmentally driven variability in per capita population growth rates,
      increasing the number of species in a community decreases the CV of combined
      species densities, provided that species do not respond to environmental
      fluctuations in a perfectly correlated way. Thus, a community with more species
      of competitors will be more stable (have lower CV in combined species densities
      for a given level of environmental variability) than a species-poor community,
      provided that the species in both communities show equal variability in per
      capita population growth rates and provided that species within each community do
      not show strongly correlated responses to environmental fluctuations. This
      conclusion also applies to "noninteractive" models in which there is no
      competition between species.

PMID- 18707424
TI  - Toward a causal explanation of plant invasiveness: seedling growth and life
      history strategies of 29 pine (Pinus) species.
AB  - We studied 29 pine (Pinus) species to test the hypothesis that invasive species
      in disturbed habitats have distinct attributes. Seedling relative growth rate
      (RGR) and measures of invasiveness were positively associated across species as
      well as within phylogenetically independent contrasts. High RGR, small seed
      masses, and short generation times characterize pine species that are successful
      invaders in disturbed habitats. Discriminant analysis and logistic regression
      revealed that RGR was the most significant factor among these life-history traits
      separating invasive and noninvasive species. We also explored the causes of
      differences in RGR among invasive and noninvasive species. While net assimilation
      rate, leaf mass ratio, and specific leaf area (SLA) were all found to be
      contributing positively to RGR, SLA was found to be the main component
      responsible for differences in RGR between invasive and noninvasive pines. We
      investigated differences in SLA further by studying leaf anatomy, leaf density,
      and leaf thickness. We also evaluated relative leaf production rate as an
      important aspect of SLA. We proposed a hypothetical causal network of all
      relevant variables.

PMID- 18707425
TI  - Coexistence in metacommunities: the regional similarity hypothesis.

PMID- 18707427
TI  - A theory of stochastic harvesting in stochastic environments.
AB  - We investigate how model populations respond to stochastic harvesting in a
      stochastic environment. In particular, we show that the effects of variable
      harvesting on the variance in population density and yield depend critically on
      the autocorrelation of environmental noise and on whether the endogenous dynamics
      of the population display over- or undercompensation to density. These factors
      interact in complicated ways; harvesting shifts the slope of the renewal
      function, and the net effect of this shift will depend on the sign and magnitude
      of the other influences. For example, when environmental noise exhibits a
      positive autocorrelation, the relative importance of a variable harvest to the
      variance in density increases with overcompensation but decreases with
      undercompensation. For a fixed harvesting level, an increasing level of
      autocorrelation in environmental noise will decrease the relative variation in
      population density when overcompensation would otherwise occur. These and other
      intricate interactions have important ramifications for the interpretation of
      time series data when no prior knowledge of demographic or environmental details
      exists. These effects are important whenever the harvesting rate is sufficiently
      high or variable, conditions likely to occur in many systems, whether the
      harvesting is caused by commercial exploitation or by any other strong agent of
      density-independent mortality.

PMID- 18707428
TI  - Predicting patterns of mating and potential hybridization from pollinator
      behavior.
AB  - Hybridization in flowering plants is determined in part by the rate at which
      animal pollinators move between species and by the effectiveness of such
      movements in transferring pollen. Pollinator behavior can also influence hybrid
      fitness by determining receipt and export of pollen. We incorporated information
      on pollinator effectiveness and visitation behavior into a simulation model that
      predicts pollen transfer between Ipomopsis aggregata, Ipomopsis tenuituba, and
      hybrids. These predictions were compared with estimates of pollen transfer
      derived from movement of fluorescent dyes in experimental plant arrays.
      Interspecific pollen transfer was relatively uncommon in these arrays, whereas
      transfer between hybrids and the parental species was at least as common as
      conspecific transfer. Backcrossing was asymmetrical; I. aggregata flowers
      frequently received mixed loads of hybrid and conspecific pollen. The simulation
      suggests that these patterns of pollen transfer are largely explained by the
      visitation sequences of hummingbird and insect pollinators, with little
      contribution from mechanical isolation. Pollen receipt by hybrids exceeded that
      of both parental species in a year when pollinators preferred to visit F(1) and
      F(2) hybrids and was intermediate in another year when they preferred to visit I.
      aggregata. This suggests that natural variation in pollination may produce
      spatiotemporal variation in hybridization and hybrid fitness.

PMID- 18707429
TI  - Altruism, dispersal, and phenotype-matching kin recognition.
AB  - We investigate the coevolution between philopatry and altruism in island-model
      populations when kin recognition occurs through phenotype matching. In saturated
      environments, a good discrimination ability is a necessary prerequisite for the
      emergence of sociality. Discrimination decreases not only with the average
      phenotypic similarity between immigrants and residents (i.e., with environmental
      homogeneity and past gene flow) but also with the sampling variance of similarity
      distributions (a negative function of the number of traits sampled). Whether
      discrimination should rely on genetically or environmentally determined traits
      depends on the apportionment of phenotypic variance and, in particular, on the
      relative values of e (the among-group component of environmental variance) and r
      (the among-group component of genetic variance, which also measures relatedness
      among group members). If r exceeds e, highly heritable cues do better.
      Discrimination and altruism, however, remain low unless philopatry is enforced by
      ecological constraints. If e exceeds r, by contrast, nonheritable traits do
      better. High e values improve discrimination drastically and thus have the
      potential to drive sociality, even in the absence of ecological constraints. The
      emergence of sociality thus can be facilitated by enhancing e, which we argue is
      the main purpose of cue standardization within groups, as observed in many social
      insects, birds, and mammals, including humans.

PMID- 18707430
TI  - The interplay between determinism and stochasticity in childhood diseases.
AB  - An important issue in the history of ecology has been the study of the relative
      importance of deterministic forces and processes noise in shaping the dynamics of
      ecological populations. We address this question by exploring the temporal
      dynamics of two childhood infections, measles and whooping cough, in England and
      Wales. We demonstrate that epidemics of whooping cough are strongly influenced by
      stochasticity; fully deterministic approaches cannot achieve even a qualitative
      fit to the observed data. In contrast, measles dynamics are extremely well
      explained by a deterministic model. These differences are shown to be caused by
      their contrasting responses to dynamical noise due to different infectious
      periods.

PMID- 18707431
TI  - On the vegetative biomass partitioning of seed plant leaves, stems, and roots.
AB  - A central goal of comparative life-history theory is to derive the general rules
      governing growth, metabolic allocation, and biomass partitioning. Here, we use
      allometric theory to predict the relationships among annual leaf, stem, and root
      growth rates (GL, GS, and GR, respectively) across a broad spectrum of seed plant
      species. Our model predicts isometric scaling relationships among all three organ
      growth rates: GL is proportional to GS is proportional to GR. It also provides a
      conceptual basis for understanding the differences in the absolute amounts of
      biomass allocated to construct the three organ types. Analyses of a large
      compendium of biomass production rates across diverse seed plant species provide
      strong statistical support for the predictions of the theory and indicate that
      reproductive investments may scale isometrically with respect to vegetative organ
      growth rates. The general rules governing biomass allocation as indexed by the
      scaling exponents for organ growth rates are remarkably indifferent to plant size
      and taxonomic affiliation. However, the allometric "constants" for these
      relationships differ numerically as a function of phenotypic features and local
      environmental conditions. Nonetheless, at the level of both inter- and
      intraspecific comparisons, the same proportional biomass allocation pattern holds
      across extant seed plant species.

PMID- 18707432
TI  - Competition and coexistence in regional habitats.
AB  - Habitat heterogeneity plays a key role in the dynamics and structures of
      communities. In this article, a two-species metapopulation model that includes
      local competitive dynamics is analyzed to study the population dynamics of two
      competing species in spatially structured habitats. When local stochastic
      extinction can be ignored, there are, as in Lotka-Volterra equations, four
      outcomes of interspecific competition in this model. The outcomes of competition
      depend on the competitive intensity between the competing pairs. An inferior
      competitor and a superior competitor, or two strongly competing species, can
      never stably coexist, whereas two weak competitors (even if they are very similar
      species) may coexist over the long term in such environments. Local stochastic
      extinction may greatly affect the outcomes of interspecific competition. Two
      competing species can or cannot stably coexist depending not only on the
      competitive intensity between the competing pairs but also on their
      precompetitive distributions. Two weak competitors that have similar
      precompetitive distributions can always regionally coexist. Two strongly
      competing species that competitively exclude each other in more stable habitats
      may be able to stably coexist in highly heterogenous environments if they have
      similar precompetitive distributions. There is also a chance for an inferior
      competitor to coexist regionally or even to exclude a superior competitor when
      the superior competitor has a narrow precompetitive distribution and the inferior
      competitor has a wide precompetitive distribution.

PMID- 18707433
TI  - The regulation of foraging activity in red harvester ant colonies.
AB  - Behavioral plasticity in social insects is intriguing because colonies adjust to
      environmental change through the aggregated responses of individuals. Without
      central control, colonies adjust numbers of workers allocated to various tasks.
      Individual decisions are based on local information from the environment and
      other workers. This study examines how colonies of the seed-eating ant
      Pogonomyrmex barbatus adjust the intensity of foraging in an arid environment
      where conspecific neighbors compete for foraging area. The main question is how
      foragers decide whether to leave the nest. Patrollers search the area before
      foragers emerge. Removal experiments show that the return of the patrollers
      stimulates the onset of foraging, and later, the rate at which foragers return
      affects the rate at which foragers continue to leave the nest. Foraging activity
      is less sensitive to changes in the rate of returning foragers than to changes in
      the rate of returning patrollers. These results suggest that whether a colony
      forages at all on a given day depends on conditions detected early by patrollers
      but that once foraging begins, the intensity of foraging does not track, on an
      hourly timescale, how quickly foragers can find food.

PMID- 18707434
TI  - Effects of acquired immunity and mating strategy on the genetic structure of
      parasite populations.
AB  - Although it may have profound effects on how researchers seek to tackle many
      infectious diseases, little is known of the genetic structure of many pathogen
      populations. Previous models have suggested that if levels of cross-protection
      are high, parasite populations may be structured into discrete strains with
      nonoverlapping antigenic repertoires, even among populations that reproduce
      sexually. Here, I consider a discrete model of the coevolution of parasites with
      host-acquired immunity. In this model, if the effective recombination rate is
      low, strain structure can be maintained for very high levels of cross-protection.
      However, if the effective recombination rate is higher, this strain structure can
      no longer be maintained. The effective recombination rate is affected by the
      actual recombination rate between immunologically selected loci, the proportion
      of individuals that reproduce sexually, whether recombination occurs inside or
      outside of the host or vector, and the level of cross-protection. The model
      predicts that for Plasmodium falciparum, where reproduction occurs inside of a
      vector, we expect to see strain structure in areas of low transmission but not in
      areas of high transmission. Strain structure is unlikely to be seen in parasites
      that reproduce outside of a host or vector, such as Strongyloides ratti.

PMID- 18707435
TI  - A formula for the mean lifetime of metapopulations in heterogeneous landscapes.
AB  - We present a formula for the mean lifetime of metapopulations in heterogeneous
      landscapes. This formula provides new insights into the effect of the spatial
      structure of habitat networks on metapopulation survival, with consequences for
      modeling, landscape evaluation, and metapopulation management. In the whole
      study, the spatially realistic metapopulation model of Frank and Wissel is taken
      as a basis. First, as a key result on the way toward the desired formula, it is
      shown that a simple nonspatial (Levins-type) model is able to reproduce the
      behavior of the complex spatial model considered regarding the mean lifetime,
      provided its parameters appropriately summarize all the relevant details of
      spatial heterogeneity. Second, the formula presented reveals how data from
      species and landscape have to be combined to estimate the survival chance of a
      metapopulation without having to run any simulation or to solve numerically any
      model equation. Third, by taking the formula as a basis, landscape measures are
      derived that allow dissimilar habitat networks to be evaluated, compared, and
      ranked in terms of their effect on metapopulation survival. Fourth, a combination
      of analytical, nonlinear regression as well as aggregation techniques was used to
      deduce the formula presented. The potential of these techniques for simplifying
      (meta)population models that are complex due to spatial heterogeneity is
      discussed.

PMID- 18707436
TI  - Induction of preference and performance after acclimation to novel hosts in a
      phytophagous spider mite: adaptive plasticity?
AB  - We examined induction of preference and performance on novel host plants for two
      laboratory populations of the polyphagous spider mite Tetranychus urticae, with
      one population adapted to bean and the other population adapted to tomato. We
      bred four isofemale lines of the bean population only and used them in all the
      assays. The bean population had a 30% lower fecundity on tomato than on bean,
      while the tomato population had equal fecundity on both host plants. Acclimation
      of adult females to the novel host plant for both populations increased
      acceptability of that novel host but did not increase rejection of the original
      host. The bean population experienced a 60% benefit and a 30% cost in terms of
      egg production for acclimating to tomato, thus exemplifying adaptive plasticity.
      The tomato population showed a 23% benefit for acclimating to bean but no cost.
      Mites from the bean population that were acclimated to tomato fed more on tomato
      than did mites that were not acclimated to tomato. When these mites were fed
      inhibitors of cytochrome P-450 detoxification enzymes, their performance was
      severely depressed (84%) on tomato but not on bean. However, mites that were fed
      inhibitors of P-450 enzymes did not reduce their acceptance of tomato as a host.
      Thus, performance on novel hosts (but not preference) in this species is likely
      correlated with the induction of detoxifying enzymes. Spider mites are known to
      form host races rapidly on novel hosts. Induction of preference and physiological
      acclimation via detoxification enzymes may enhance performance and, thus,
      strongly contribute to initial stages of host race formation.

PMID- 18707437
TI  - Species richness, environmental correlates, and spatial scale: a test using South
      African birds.
AB  - Energy and habitat heterogeneity are important correlates of spatial variation in
      species richness, though few investigations have sought to determine
      simultaneously their relative influences. Here we use the South African avifauna
      to examine the extent to which species richness is related to these variables and
      how these relationships depend on spatial grain. Taking spatial autocorrelation
      and area effects into account, we find that primary productivity, precipitation,
      absolute minimum temperature, and, at coarser resolutions, habitat heterogeneity
      account for most of the variation in species richness. Species richness and
      productivity are positively related, whereas the relationship between potential
      evapotranspiration (PET) and richness is unimodal. This is largely because of the
      constraining effects of low rainfall on productivity in high-PET areas. The
      increase in the importance of vegetation heterogeneity as an explanatory variable
      is caused largely by an increase in the range of vegetation heterogeneity
      included at coarse resolutions and is probably also a result of the positive
      effects of environmental heterogeneity on species richness. Our findings indicate
      that species richness is correlated with, and hence likely a function of, several
      variables, that spatial resolution and extent must be taken into account during
      investigations of these relationships, and that surrogate measures for
      productivity should be interpreted cautiously.

PMID- 18707439
TI  - The evolution of parental care in the context of sexual selection: a critical
      reassessment of parental investment theory.
AB  - Males and females are often defined by differences in their energetic investment
      in gametes. In most sexual species, females produce few large ova, whereas males
      produce many tiny sperm. This difference in initial parental investment is
      presumed to exert a fundamental influence on sex differences in mating and
      parental behavior, resulting in a taxonomic bias toward parental care in females
      and away from parental care in males. In this article, we reexamine the logic of
      this argument as well as the evolutionarily stable strategy (ESS) theory often
      used to substantiate it. We show that the classic ESS model, which contrasts
      parental care with offspring desertion, violates the necessary relationship
      between mean male and female fitness. When the constraint of equal male and
      female mean fitness is correctly incorporated into the ESS model, its results are
      congruent with those of evolutionary genetic theory for the evolution of genes
      with direct and indirect effects. Male parental care evolves whenever half the
      magnitude of the indirect effect of paternal care on offspring viability exceeds
      the direct effect of additional mating success gained by desertion. When the
      converse is true, desertion invades and spreads. In the absence of a genetic
      correlation between the sexes, the evolution of paternal care is independent of
      maternal care. Theories based on sex differences in gametic investment make no
      such specific predictions. We discuss whether inferences about the evolution of
      sex differences in parental care can hold if the ESS theory on which they are
      based contains internal contradictions.

PMID- 18707440
TI  - Will small population sizes warn us of impending extinctions?
AB  - Several models are used to show that population sizes are often relatively
      insensitive to deteriorating environmental conditions over most of the range of
      environments that allow population persistence. As conditions continue to worsen
      in these cases, equilibrium population sizes ultimately decline rapidly toward
      extinction from sizes similar to or larger than those before environmental
      decline began. Consumer-resource models predict that equilibrium or average
      population size can increase with deteriorating environmental conditions over a
      large part of the range of the environmental parameter that allows persistence.
      The initial insensitivity or increase in the population of the focal species
      occurs because changes in the populations of other components of the food web
      compensate for the decline in one or more fitness components of the focal
      population. However, the compensatory processes are generally nonlinear and often
      approach their limits abruptly rather than gradually. When there is steady
      directional change in the environment, populations lag behind the equilibrium
      population size specified by current environmental conditions. The environmental
      variable can then decline below the level required for population persistence
      while the population size is still close to or greater than its original value.
      Efficient consumers and self-reproducing resources are especially likely to
      produce this outcome. More complex models with adaptive behavior, additional
      consumers, or additional resources often exhibit similar trajectories of
      population size under environmental deterioration.

PMID- 18707441
TI  - A model for optimal reaction norms: the case of the pregnant garter snake and her
      temperature-sensitive embryos.
AB  - We present a model to test Osgood's ( 1978 ) proposition that viviparous snakes
      have optimal reaction norms for temperature-sensitive meristic traits, such as
      scale counts. Our model predicts that traits that are subject to temperature
      effects during development will evolve a flat or [Formula: see text]-shaped
      reaction norm (average scale count as a function of developmental temperature).
      We tested this prediction by maintaining 67 female garter snakes (Thamnophis
      elegans) at eight different constant temperatures (21 degrees -33 degrees C)
      during pregnancy and making a series of scale counts on their newborn offspring
      (n = 491). To insure that the experimental temperatures were ecologically
      relevant, we used automated radiotelemetry to record the body temperature of
      pregnant, free-ranging females. The resulting temperature data allowed us to test
      the prediction that the inflection points of reaction norms would correspond to
      the average temperature experienced by embryos in the field. In line with
      predictions of the Osgood model, reaction norms were flat or U-shaped. In the
      case of U-shaped reaction norms, the inflection point of the curves corresponded
      to the average temperature imposed on embryos by free-ranging females. In
      contrast to some past studies, none of the standard scale scores (ones commonly
      used in systematics) showed significant temperature effects in either sex.
      Reaction norms were flat. In contrast, incidences of various abnormalities showed
      U-shaped reaction norms. Temperature effects were more pronounced in males than
      in females. The results have implications for systematics and for the evolution
      of canalization and phenotypic plasticity.

PMID- 18707442
TI  - Floristic relationships between Eastern Asia and North America: test of Gray's
      hypothesis.
AB  - Similarities in the temperate floras of eastern Asia and North America have been
      appreciated for more than 200 yr, but the generality of the floristic
      relationships among eastern Asia (EAS), eastern North America (ENA), and western
      North America (WNA), postulated by Asa Gray about 150 yr ago, has not been tested
      until now. In this article, floristic relationships based on genera shared among
      EAS, ENA, and WNA were examined at different spatial scales for different
      phylogenetic groups using complete floras. Floristic similarity between EAS and
      ENA is higher than that between EAS and WNA, and the floras of ENA and WNA are
      more closely related to each other than are the floras of EAS and ENA. Compared
      with ENA and WNA, the number of genera common to EAS and ENA is significantly
      higher in basal angiosperms and significantly lower in asterids. Floristic
      similarities tend to decrease from more basal to more modern lineages between EAS
      and ENA and between EAS and WNA but not between ENA and WNA. Similarly, from more
      basal to more modern divisions, the fraction of shared genera decreases between
      EAS and ENA and between EAS and WNA, whereas the floristic similarity between ENA
      and WNA tends to increase. Furthermore, floristic similarity between EAS and ENA
      increases with latitude. The causes of the observed patterns of floristic
      similarity between EAS, ENA, and WNA are discussed.

PMID- 18707443
TI  - Evolutionary consequences of asymmetric dispersal rates.
AB  - We study the consequences of asymmetric dispersal rates (e.g., due to wind or
      current) for adaptive evolution in a system of two habitat patches. Asymmetric
      dispersal rates can lead to overcrowding of the "downstream" habitat, resulting
      in a source-sink population structure in the absence of intrinsic quality
      differences between habitats or can even cause an intrinsically better habitat to
      function as a sink. Source-sink population structure due to asymmetric dispersal
      rates has similar consequences for adaptive evolution as a source-sink structure
      due to habitat quality differences: natural selection tends to be biased toward
      the source habitat. We demonstrate this for two models of adaptive evolution:
      invasion of a rare allele that improves fitness in one habitat but reduces it in
      the other and antagonistic selection on a quantitative trait determined by five
      additive loci. If a habitat can sustain a population without immigration, the
      conditions for adaptation to that habitat are most favorable if there is little
      or no immigration from the other habitat; the influence of emigration depends on
      the magnitude of the allelic effects involved and other parameters. If, however,
      the population is initially unable to persist in a given habitat without
      immigration, our model predicts that the population will be most likely to adapt
      to that habitat if the dispersal rates in both directions are high. Our results
      highlight the general message that the effect of gene flow upon local adaptation
      should depend profoundly on the demographic context of selection.

PMID- 18707444
TI  - Stage-structured infection transmission and a spatial epidemic: a model for Lyme
      disease.
AB  - A greater understanding of the rate at which emerging disease advances spatially
      has both ecological and applied significance. Analyzing the spread of vector
      borne disease can be relatively complex when the vector's acquisition of a
      pathogen and subsequent transmission to a host occur in different life stages. A
      contemporary example is Lyme disease. A long-lived tick vector acquires infection
      during the larval blood meal and transmits it as a nymph. We present a reaction
      diffusion model for the ecological dynamics governing the velocity of the current
      epidemic's spread. We find that the equilibrium density of infectious tick nymphs
      (hence the risk of human disease) can depend on density-independent survival
      interacting with biotic effects on the tick's stage structure. The local risk of
      infection reaches a maximum at an intermediate level of adult tick mortality and
      at an intermediate rate of juvenile tick attacks on mammalian hosts. If the
      juvenile tick attack rate is low, an increase generates both a greater density of
      infectious nymphs and an increased spatial velocity. However, if the juvenile
      attack rate is relatively high, nymph density may decline while the epidemic's
      velocity still increases. Velocities of simulated two-dimensional epidemics
      correlate with the model pathogen's basic reproductive number (R0), but
      calculating R0 involves parameters of both host infection dynamics and the
      vector's stage-structured dynamics.

PMID- 18707445
TI  - Which way to manipulate host reproduction? Wolbachia that cause cytoplasmic
      incompatibility are easily invaded by sex ratio-distorting mutants.
AB  - The bacterium Wolbachia manipulates its hosts by inducing cytoplasmic
      incompatibility (CI), where zygotes formed from crosses between uninfected
      mothers and infected fathers die. In addition, it distorts the host's sex ratio
      via male killing, parthenogenesis induction, or feminization. Here, we model
      transitions between these states, examining the evolution of mutants of CI
      strains that retain both the ability to induce and resist CI but, in addition,
      cause sex ratio distortion. The model shows that CI strains are highly
      susceptible to invasion and subsequent elimination by these mutants. For all
      three types of sex ratio distortion, there is some parameter space in which the
      strain showing sex ratio distortion becomes extinct following exclusion of the
      progenitor CI strain, leaving the population uninfected. Extinction of the new
      Wolbachia strain is common for the case of male killing but rarer for
      parthenogenesis induction and feminization. Our models predict that CI strains of
      Wolbachia will occur most commonly in hosts that are male heterogametic, where
      there is little interaction between siblings because these hosts are unlikely to
      favor the spread of male killing, feminization, or parthenogenesis induction. The
      models raise the question of why CI strains apparently predominate in nature, and
      it is suggested that this is a result of either fewer restrictions on CI strains
      spreading through novel host populations or restrictions to the mutability of
      Wolbachia strains.

PMID- 18707446
TI  - Coevolution between parasite virulence and host life-history traits.
AB  - Epidemiological models generally explore the evolution of parasite life-history
      traits, namely, virulence and transmission, against a background of constant host
      life-history traits. However, life-history models have predicted the evolution of
      host traits in response to parasitism. The coevolution of host and parasite life
      history traits remains largely unexplored. We present an epidemiological model,
      based on resource allocation theory, that provides an analysis of the coevolution
      between host reproductive effort and parasite virulence. This model allows for
      hosts with either a fixed (i.e., genetic) or conditional (i.e., a phenotypically
      plastic) response to parasitism. It also considers superinfections. We show that
      parasitism always favors increased allocation to host reproduction, but because
      of epidemiological feedbacks, the evolutionarily stable host reproductive effort
      does not always increase with parasite virulence. Superinfection drives the
      evolution of parasite virulence and acts on the evolution of the host through
      parasite evolution, generally leading to higher host reproductive effort.
      Coevolution, as opposed to cases where only one of the antagonists evolves, may
      generate correlations between host and parasite life-history traits across
      environmental gradients affecting the fecundity or the survival of the host. Our
      results provide a theoretical framework against which experimental coevolution
      outcomes or field observations can be contrasted.

PMID- 18707447
TI  - The effects of small dispersal rates on extinction times in structured
      metapopulation models.
AB  - Habitat destruction is a critical factor that affects persistence in several
      taxa, including Pacific salmon. Salmon are noted for their ability to home to
      their natal streams for reproduction. Since straying (i.e., spawners reproducing
      in nonnatal streams) is typically low in salmon, its effects have not been
      appreciated. In this article, we develop both a general analytical model and a
      simple simulation model describing structured metapopulations to study how weak
      connections between subpopulations affect the ability of a species to tolerate
      habitat destruction and/or declines in habitat quality. Our goals are to develop
      general principles and to relate these principles to salmon population dynamics.
      The analytical model describes the dynamics of two density-dependent
      subpopulations, connected by dispersal, whose growth rates fluctuate in response
      to environmental and demographic stochasticity. We find that, for moderate levels
      of environmental variability, small dispersal rates can significantly increase
      mean extinction times. This effect declines with increasing habitat quality,
      increasing temporal correlation, and increasing spatial correlation, but it is
      still significant for realistic parameter values. The simulation model shows
      there is a threshold rate of dispersal that minimizes extinction probabilities.
      These results cannot be seen in classical metapopulation models and provide new
      insights into the rescue effect.

PMID- 18707448
TI  - Socially structured populations and evolution of recombination under antagonistic
      coevolution.

PMID- 18707449
TI  - The ubiquitous and varied role of infection in the lives of animals and plants.
AB  - Parasitic and symbiotic infections are major forces governing the life histories
      of plant and animal hosts-a fact that is ever more evident because of recent
      findings emanating from diverse subdisciplines of biology. Yet, infectious
      organisms have been relatively little investigated by biologists who study
      natural populations. Now that new molecular and computational tools allow us to
      differentiate and track microscopic infectious agents in nature, we are beginning
      to establish a better appreciation of their effects on larger, more familiar
      organisms. This special issue on the ecological and evolutionary consequences of
      infection for plants and animals is based on the annual Vice Presidential
      Symposium at the meeting of the American Society of Naturalists held in
      Knoxville, Tennessee, in the summer of 2001.

PMID- 18707450
TI  - Ecology and evolution of multigenomic arbuscular mycorrhizal fungi.
AB  - Arbuscular mycorrhizal fungi (AMF) form extremely important mutualistic symbioses
      with most plants. Their role in nutrient acquisition, plant community structure,
      plant diversity, and ecosystem productivity and function has been demonstrated in
      recent years. New findings on the genetics and biology of AMF also give us a new
      picture of how these fungi exist in ecosystems. In this article, I bring together
      some recent findings that indicate that AMF have evolved to contain multiple
      genomes, that they connect plants together by a hyphal network, and that these
      different genomes may potentially move around in this network. These findings
      show the need for more intensive studies on AMF population biology and genetics
      in order to understand how they have evolved with plants, to better understand
      their ecological role, and for applying AMF in environmental management programs
      and in agriculture. A number of key features of AMF population biology have been
      identified for future studies and most of these concern the need to understand
      drift, selection, and genetic exchange in multigenomic organisms, a task that has
      not previously presented itself to evolutionary biologists.

PMID- 18707451
TI  - Ecology and evolution of host-parasite associations: mycophagous Drosophila and
      their parasitic nematodes.
AB  - Associations between mycophagous Drosophila and nematode parasites occur
      throughout the temperate and boreal regions of North America, Europe, and Asia.
      The nematode Howardula aoronymphium has substantial adverse effects on host
      survival and fertility on North American Drosophila. Long-term data show that
      rainy summers lead to a high prevalence of parasitism in the fall and the
      following spring, resulting in up to a 1-yr time lag between present rainfall and
      increased prevalence of H. aoronymphium parasitism. A biogeographic analysis of
      the relative abundance of different Drosophila species has shown that H.
      aoronymphium may facilitate the coexistence of different species of Drosophila
      that compete for larval food resources. The actual host range of parasites in
      nature is determined by the intrinsic suitability of potential hosts for parasite
      infection and reproduction and various ecological factors. For H. aoronymphium in
      eastern North America, intrinsically suitable hosts fall within a restricted
      clade within the genus Drosophila. However, the temperature sensitivity of H.
      aoronymphium prevents it from using several host species that occur outside the
      geographical range of the nematodes. Finally, the host range, virulence, and
      geographical range of Drosophila-parasitic nematodes appear to be highly dynamic
      over evolutionary timescales.

PMID- 18707452
TI  - The ecology and genetics of a host shift: microbotryum as a model system.
AB  - The need to prevent and cure emerging diseases often precludes their continuing
      study in situ. We present studies on the process of disease emergence by host
      shifts using the model system of anther-smut disease (Microbotryum violaceum) on
      the plant genus Silene (Caryophyllaceae). This system has little direct social
      impact, and it is readily amenable to experimental manipulation. Our
      microevolutionary studies have focused on the host shift of Microbotryum from
      Silene alba (=latifolia; white campion) onto Silene vulgaris (bladder campion) in
      a population in Virginia. Karyotypic variation shows that the host shift is
      recent and originates from the disease on sympatric S. alba. Analysis of the
      spatial pattern of disease shows that the host shift has been contingent on the
      co-occurrence of the two species at a local scale. Cross-inoculation studies show
      that families of the new host differ greatly in their susceptibility to the
      pathogen, indicating the potential for rapid evolution of resistance. Disease
      expression on the new host is frequently abnormal, suggesting that the pathogen
      is imperfectly adapted to its new host. In experimental populations, disease
      transmission within populations of the old host is greater than within
      populations of the new host. However, there is also a high transmission rate of
      the disease from the new host back to the old host, suggesting a feedback effect
      that increases disease prevalence in the community as a whole. Continuing studies
      of these populations are designed to determine whether this new host-pathogen
      system is likely to be self-sustaining and to quantify evolutionary changes in
      both the host and the pathogen.

PMID- 18707453
TI  - The effect of Wolbachia on genetic divergence between populations: models with
      two-way migration.
AB  - Wolbachia are intracellular bacteria that cause various reproduction alterations
      in their hosts, including cytoplasmic incompatibility (CI), an incompatibility
      between sperm and egg that typically results in embryonic death. We investigate
      theoretically the effects of Wolbachia-induced bidirectional CI on levels of
      divergence between two populations, where there is migration in both directions
      and differential selection at a single locus. The main findings are as follows:
      Wolbachia differences in the two populations are maintained up to a threshold
      migration rate, above which the system collapses to a single Wolbachia type;
      differential selection at a nuclear locus increases the threshold migration rate
      below which Wolbachia polymorphisms are maintained; Wolbachia differences between
      the populations enhance their genetic divergence at the selected locus by
      reducing the "effective migration rate," and even moderate levels of CI can cause
      large population differences in allele frequencies; and asymmetric CI can induce
      strong asymmetries in effective migration rate and dramatically alter the pattern
      of genetic divergence compared with the No Wolbachia situation. We derive an
      analytical approximation for the effective migration rate, which matches the
      simulation results for most parameter values. These results generally support the
      view that CI Wolbachia can contribute to genetic divergence between populations.

PMID- 18707454
TI  - Ant versus fungus versus mutualism: ant-cultivar conflict and the deconstruction
      of the attine ant-fungus symbiosis.
AB  - A century of research on fungus-growing ants (Attini, Formicidae) has ignored the
      cultivated fungi as passive domesticates and viewed the attine fungicultural
      symbiosis as an integrated unit dominated by the evolutionary interests of the
      ant farmers. This article takes a different perspective and explores first the
      evolutionary interests and leverages of the fungal cultivars, then dissects eight
      potential evolutionary conflicts between ants and cultivars. Three types of ant
      cultivar conflict are examined in depth. First, ant-cultivar conflict over the
      ant sex ratio is predicted because the cultivars are dispersed by female
      foundresses but not by males; cultivars thus may be selected to bias the ant sex
      ratio toward females. Second, ant-cultivar conflict over fungal sexual
      reproduction exists if the fungi are able to escape from the symbiosis and live
      independently, as is implied by phylogenetic analyses of the fungi; this conflict
      is exacerbated in colonies that experience queen death or senescence. A
      literature review reveals that sexual fruiting of attine cultivars is more common
      than has been traditionally realized and often occurs in moribund colonies.
      Third, the routine transplanting of fungal mycelium by ants could generate,
      through sensory-biased symbiont choice, selection favoring fungal features that
      increase the likelihood of transplantation within nests (symbiont drive) but that
      are detrimental to the survival of the whole colony. A balanced perspective
      incorporating both ant and fungal interests emerges as a more appropriate
      framework than the traditional myrmicocentric perspective. Indeed, the attine
      symbiosis offers unique experimental opportunities (cultivar switch experiments)
      to unravel the evolutionary dynamics of conflict and cooperation between ant and
      fungal partners.

PMID- 18707455
TI  - Immune defense and host life history.
AB  - Recent interest has focused on immune response in an evolutionary context, with
      particular attention to disease resistance as a life-history trait, subject to
      trade-offs against other traits such as reproductive effort. Immune defense has
      several characteristics that complicate this approach, however; for example,
      because of the risk of autoimmunity, optimal immune defense is not necessarily
      maximum immune defense. Two important types of cost associated with immunity in
      the context of life history are resource costs, those related to the allocation
      of essential but limited resources, such as energy or nutrients, and option
      costs, those paid not in the currency of resources but in functional or
      structural components of the organism. Resource and option costs are likely to
      apply to different aspects of resistance. Recent investigations into possible
      trade-offs between reproductive effort, particularly sexual displays, and
      immunity have suggested interesting functional links between the two. Although
      all organisms balance the costs of immune defense against the requirements of
      reproduction, this balance works out differently for males than it does for
      females, creating sex differences in immune response that in turn are related to
      ecological factors such as the mating system. We conclude that immune response is
      indeed costly and that future work would do well to include invertebrates, which
      have sometimes been neglected in studies of the ecology of immune defense.

PMID- 18707456
TI  - Evolutionary origins and ecological consequences of endophyte symbiosis with
      grasses.
AB  - Over the past 20 yr much has been learned about a unique symbiotic interaction
      between fungal endophytes and grasses. The fungi (Clavicipitaceae, Ascomycota)
      grow intercellularly and systemically in aboveground plant parts. Vertically
      transmitted asexual endophytes forming asymptomatic infections of cool-season
      grasses have been repeatedly derived from sexual species that abort host
      inflorescences. The phylogenetic distribution of seed-transmitted endophytes is
      strongly suggestive of cocladogenesis with their hosts. Molecular evidence
      indicates that many seed-transmitted endophytes are interspecific hybrids.
      Superinfection may result in hyphal fusion and parasexual recombination. Most
      endophytes produce one or more alkaloid classes that likely play some role in
      defending the host plant against pests. Hybridization may have led to the
      proliferation of alkaloid-production genes among asexual endophytes, favoring
      hybrids. The ergot alkaloid ergovaline, lolitrems, and lolines are produced by
      only a single sexual species, Epichloe festucae, but they are common in seed
      transmitted endophytes, suggesting that E. festucae contributed genes for their
      synthesis. Asexual hybrids may also be favored by the counteracting of the
      accumulation of deleterious mutations (Muller's rachet). Endophyte infection can
      provide other benefits, such as enhanced drought tolerance, photosynthetic rate,
      and growth. Estimates of infection frequency have revealed variable levels of
      infection with especially high prevalence in the subfamily Pooideae. Longitudinal
      studies suggest that the prevalence of seed-transmitted endophytes can increase
      rapidly over time. In field experiments, infected tall fescue suppressed other
      grasses and forbs relative to uninfected fescue and supported lower consumer
      populations. Unlike other widespread plant/microbial symbioses based on the
      acquisition of mineral resources, grass/endophyte associations are based
      primarily on protection of the host from biotic and abiotic stresses.

PMID- 18707459
TI  - Why alien invaders succeed: support for the escape-from-enemy hypothesis.
AB  - Successful biological invaders often exhibit enhanced performance following
      introduction to a new region. The traditional explanation for this phenomenon is
      that natural enemies (e.g., competitors, pathogens, and predators) present in the
      native range are absent from the introduced range. The purpose of this study was
      to test the escape-from-enemy hypothesis using the perennial plant Silene
      latifolia as a model system. This European native was introduced to North America
      in the 1800s and subsequently spread to a large part of the continent. It is now
      considered a problematic weed of disturbed habitats and agricultural fields in
      the United States and Canada. Surveys of 86 populations in the United States and
      Europe revealed greater levels of attack by generalist enemies (aphids, snails,
      floral herbivores) in Europe compared with North America. Two specialists (seed
      predator, anther smut fungus) that had dramatic effects on plant fitness in
      Europe were either absent or in very low frequency in North America. Overall,
      plants were 17 times more likely to be damaged in Europe than in North America.
      Thus, S. latifolia's successful North American invasion can, at least in part, be
      explained by escape from specialist enemies and lower levels of damage following
      introduction.

PMID- 18707460
TI  - Phylogenetic analysis and comparative data: a test and review of evidence.
AB  - The question is often raised whether it is statistically necessary to control for
      phylogenetic associations in comparative studies. To investigate this question,
      we explore the use of a measure of phylogenetic correlation, lambda, introduced
      by Pagel (1999), that normally varies between 0 (phylogenetic independence) and 1
      (species' traits covary in direct proportion to their shared evolutionary
      history). Simulations show lambda to be a statistically powerful index for
      measuring whether data exhibit phylogenetic dependence or not and whether it has
      low rates of Type I error. Moreover, lambda is robust to incomplete phylogenetic
      information, which demonstrates that even partial information on phylogeny will
      improve the accuracy of phylogenetic analyses. To assess whether traits generally
      show phylogenetic associations, we present a quantitative review of 26 published
      phylogenetic comparative data sets. The data sets include 103 traits and were
      chosen from the ecological literature in which debate about the need for
      phylogenetic correction has been most acute. Eighty-eight percent of data sets
      contained at least one character that displayed significant phylogenetic
      dependence, and 60% of characters overall (pooled across studies) showed
      significant evidence of phylogenetic association. In 16% of tests, phylogenetic
      correlation could be neither supported nor rejected. However, most of these
      equivocal results were found in small phylogenies and probably reflect a lack of
      power. We suggest that the parameter lambda be routinely estimated when analyzing
      comparative data, since it can also be used simultaneously to adjust the
      phylogenetic correction in a manner that is optimal for the data set, and we
      present an example of how this may be done.

PMID- 18707461
TI  - The energetics and scaling of search strategies in bacteria.
AB  - The influence of body size on the energetic cost of movement is well studied in
      animals but has been rarely investigated in bacteria. Here, I calculate the cost
      of four chemotactic strategies for different-sized bacteria by adding the costs
      of their locomotion and reorientation. Size differences of 0.1 microm result in
      100,000-fold changes in the energetic cost of chemotaxis. The exact cost for any
      given size is a nonlinear function of flagella length, the minimum speed
      necessary to detect and respond to a signal, and the gradient of the signal.
      These parameters are interlinked in such a way that body size and strategy are
      tightly coupled to particular environmental gradients, offering avenues for
      explaining and exploring diversity and competition. The analysis here has
      implications beyond bacteria. Power-law regression through the minimum costs of
      transport for different kinds of chemotaxis has the same slope as that for
      swimming animals, suggesting a universal allometric equation for all swimming
      organisms.

PMID- 18707462
TI  - A spatial and temporal approach to microevolutionary forces affecting population
      biology in the freshwater snail Biomphalaria pfeifferi.
AB  - The limitations of both population demography and genetics highlight the need to
      combine these approaches when inferring the influence of demographic processes
      and modes of migration on genetic structure. The aim of this study was to use
      spatiotemporal genetic and demographic surveys to reveal the microevolutionary
      forces acting on the metapopulation dynamics of the freshwater snail Biomphalaria
      pfeifferi. We also analyzed the consequences of population turnover on temporal
      genetic differentiation, an aspect that has been little explored. Genetic drift
      was revealed by both the demographic survey, which indicated severe bottlenecks
      or extinction during the rainy (resp. dry) season in open (resp. closed)
      habitats, and the genetic approach, which indicated high selfing rates and strong
      temporal differentiation. Genetic reassignments and temporal differentiation both
      confirmed the results of the demographic survey, which suggests that migration
      occurs in closed (resp. open) habitats during the hot and dry (resp. rainy)
      season, and indicated that source-sink functioning may be envisaged. A propagule
      pool mode of colonization was inferred in the open habitats during the rainy
      season and a migrant pool in the closed habitats during the dry season. Our study
      also suggests that selection might be inferred from patterns of neutral genetic
      markers when recombination is limited.

PMID- 18707463
TI  - Does within-population variation in fish egg size reflect maternal influences on
      optimal values?
AB  - Various models that assume correlations between maternal phenotype and offspring
      environment predict adaptive variation in egg size within populations. Here we
      conduct a comparative test of these models using published data on fish egg size.
      Intrapopulation variation in egg size was most pronounced in fish with demersal
      eggs and larvae (median coefficient of variation [CV] at family level = 6.5%),
      where offspring environment is likely influenced by maternal phenotype, and least
      so in fish with pelagic eggs (CV = 3.6%), which experience a relatively
      stochastic spatial distribution during incubation. This difference was
      significant at various taxonomic levels, was robust to variation in mean egg size
      and habitat (i.e., freshwater or marine), and was mirrored in independent paired
      contrasts. Fish with demersal eggs and pelagic larvae were not significantly
      different from those with pelagic eggs (CV = 3.8%), indicating that selection
      favoring within-population variation in egg size occurs mainly posthatching and
      that any such selection occurring prehatching may be less intense. These results
      suggest that patterns of within-population variation in egg size among fish taxa
      reflect adaptive processes and that maternal effects on the egg size-fitness
      function may explain apparent discrepancies from the single-optima Smith-Fretwell
      model.

PMID- 18707464
TI  - Species invasions exceed extinctions on islands worldwide: a comparative study of
      plants and birds.
AB  - Species richness is decreasing at a global scale. At subglobal scales, that is,
      within any defined area less extensive than the globe, species richness will
      increase when the number of nonnative species becoming naturalized is greater
      than the number of native species becoming extinct. Determining whether this has
      occurred is usually difficult because detailed records of species extinctions and
      naturalizations are rare; these records often exist, however, for oceanic
      islands. Here we show that species richness on oceanic islands has remained
      relatively unchanged for land birds, with the number of naturalizations being
      roughly equal to the number of extinctions, and has increased dramatically for
      vascular plants, with the number of naturalizations greatly exceeding the number
      of extinctions. In fact, for plants, the net number of species on islands has
      approximately doubled. We show further that these patterns are robust to
      differences in the history of human occupation of these islands and to the
      possibility of undocumented species extinctions. These results suggest that
      species richness may be increasing at subglobal scales for many groups and that
      future research should address what consequences this may have on ecological
      processes.

PMID- 18707465
TI  - Nitrogen in insects: implications for trophic complexity and species
      diversification.
AB  - Disparities in nutrient content (nitrogen and phosphorus) between herbivores and
      their plant resources have lately proven to have major consequences for herbivore
      success, consumer-driven nutrient cycling, and the fate of primary production in
      ecosystems. Here we extend these findings by examining patterns of nutrient
      content between animals at higher trophic levels, specifically between insect
      herbivores and predators. Using a recently compiled database on insect nutrient
      content, we found that predators exhibit on average 15% greater nitrogen content
      than herbivores. This difference persists after accounting for variation from
      phylogeny and allometry. Among herbivorous insects, we also found evidence that
      recently derived lineages (e.g., herbivorous Diptera and Lepidoptera) have, on a
      relative basis, 15%-25% less body nitrogen than more ancient herbivore lineages
      (e.g., herbivorous Orthoptera and Hemiptera). We elaborate several testable
      hypotheses for the origin of differences in nitrogen content between trophic
      levels and among phylogenetic lineages. For example, interspecific variation in
      insect nitrogen content may be directly traceable to differences in dietary
      nitrogen (including dilution by gut contents), selected for directly in response
      to the differential scarcity of dietary nitrogen, or an indirect consequence of
      adaptation to different feeding habits. From some functional perspectives, the
      magnitude rather than the source of the interspecific differences in nitrogen
      content may be most critical. We conclude by discussing the implications of the
      observed patterns for both the trophic complexity of food webs and the
      evolutionary radiation of herbivorous insects.

PMID- 18707466
TI  - Bergmann's rule in ectotherms: a test using freshwater fishes.

PMID- 18707467
TI  - The parental investment strategy of an avian cooperative breeder differs between
      a fragmented and an unfragmented landscape.

PMID- 18707468
TI  - Assembly rules and competition in desert rodents.

PMID- 18707473
TI  - Genetic tools for studying adaptation and the evolution of behavior.
AB  - The rapid expansion of genomic and molecular genetic techniques in model
      organisms, and the application of these techniques to organisms that are less
      well studied genetically, make it possible to understand the genetic control of
      many behavioral phenotypes. However, many behavioral ecologists are uncertain
      about the value of including a genetic component in their studies. In this
      article, we review how genetic analyses of behavior are central to topics ranging
      from understanding past selection and predicting future evolution to explaining
      the neural and hormonal control of behavior. Furthermore, we review both new and
      old techniques for studying evolutionary behavior genetics and highlight how the
      choice of approach depends on both the question and the organism. Topics
      discussed include genetic architecture, detecting the past history of selection,
      and genotype-by-environment interactions. We show how these questions are being
      addressed with techniques including statistical genetics, QTL analyses,
      transgenic analyses, and microarrays. Many of the techniques were first applied
      to the behavior of genetic model organisms such as laboratory mice and flies. Two
      recent developments serve to expand the relevance of such studies to behavioral
      ecology. The first is to use model organisms for studies of the genetic basis of
      evolutionarily relevant behavior and the second is to apply methods developed in
      model genetic systems to species that have not previously been examined
      genetically. These conceptual advances, along with the rapid diversification of
      genetic tools and the recognition of widespread genetic homology, suggest a
      bright outlook for evolutionary genetic studies. This review provides access to
      tools through references to the recent literature and shows the great promise for
      evolutionary behavioral genetics.

PMID- 18707474
TI  - Genomics and integrative analyses of division of labor in honeybee colonies.
AB  - One approach to understanding proximate and evolutionary mechanisms of social
      behavior is to analyze mechanisms of neural and behavioral plasticity and their
      underlying genes. This article deals with such analyses in the honeybee Apis
      mellifera. The first part reviews the control of age-related division of labor in
      honeybee colonies with special attention to social, endocrine, and neurochemical
      factors. The second part reviews progress in studying changes in gene expression
      that are associated with division of labor, including a brief description of a
      genomics project that involves a set of 20,000 expressed sequence tags from the
      honeybee brain and cDNA microarrays for large-scale gene expression analysis. The
      article concludes by considering some of the general issues associated with
      studies of genes and social behavior in honeybees.

PMID- 18707475
TI  - Genetic influences on maternal care.
AB  - The basis of social evolution in mammals is the mother-offspring relationship. It
      is also the primary and most important instance of indirect genetic effects,
      where genetic variation in one individual affects phenotypic variation among
      others. This relationship is so important in mammals that often the major factor
      determining the life or death of newborns is the environment provided by their
      mother. Variations in these environments can be due to variations in maternal
      genotypes. In our work with the intercross of two mouse inbred strains, LG/J and
      SM/J, we uncovered a very severe variation in maternal performance. These females
      failed to nurture their offspring and showed abnormal maternal behaviors leading
      to loss of their litter. Rather than this being due to a single gene variant as
      in knockout mice, we uncovered a complex genetic basis for this trait. The
      effects of genes on maternal performance are entirely context dependent in our
      cross. They depend on the alleles present at the same or other epistatically
      interacting loci. Genomic locations identified in this study include locations of
      candidate genes whose knockouts displayed similar aberrant maternal behavior.
      Behaviors significantly associated with maternal performance in this study
      include suckling, nest building, placentophagia, pup grooming, and retrieval of
      pups after disturbance.

PMID- 18707476
TI  - The evolution of interacting phenotypes: genetics and evolution of social
      dominance.
AB  - Although the argument over genetic influences on social dominance is contentious,
      genetic models of interacting phenotypes provide a theoretical framework for
      heritable effects on, and therefore evolution of, social behavior. Here we adapt
      the interacting phenotype model to show how social dominance can evolve. Our
      model makes a number of predictions: rapid evolution of behavior, strong
      correlated responses in associated traits (such as a badge of status), and,
      because context is important for social dominance, integrated evolution of both
      dominant and subordinate behavior reflecting direct and indirect genetic effects
      and social selection. We also describe the results of empirical work, artificial
      selection based on social status within a hierarchy in the cockroach Nauphoeta
      cinerea, that we used to test the predictions of our model. There was little
      change within selection lines in the expression of agonistic behavior, but by
      just generation 7 of selection, in comparisons between lines, high-line males
      consistently dominated low and control males, while low-line males were
      consistently subordinate to high-line and control males. There was a strong
      correlated response to selection in the pheromonal badge of status. Some
      correlated responses to selection differed among replicate lines, with the
      compound that makes males subordinate changed in one replicate, while the
      compound that confers dominance was altered in the other. Overall, our results
      are consistent with predictions from models of interacting phenotypes: social
      dominance is influenced by additive genetic variation, can evolve as a result of
      social selection, and evolution of social interactions appears to be rapid.
      Finally, different responses in the replicates allowed us to test very specific
      predictions regarding the role of the social pheromone in N. cinerea,
      highlighting the value of artificial selection experiments as a tool in
      evolutionary behavioral genetic studies.

PMID- 18707477
TI  - Nonadditive genetic effects in animal behavior.
AB  - Heritabilities, commonly used to predict evolutionary potential, are notoriously
      low for behaviors. Apart from strong contributions of environmental variance in
      reducing heritabilities, the additive genetic components can be very low,
      especially when they are camouflaged by nonadditive genetic effects. We first
      report the heritabilities of courtship traits in founder-flush and control
      populations of the housefly (Musca domestica L.). We estimated the heritability
      of each male and female display through the regression of the courtships
      involving daughters and sons (with randomly selected mates) onto the
      "midparental" courtship values of their parents. Overall, the average
      heritability was significantly (P = .012) higher for the parent-daughter assays
      than for the parent-son assays. We attributed the low (even negative)
      heritabilities to genotype-by-environment interactions whereby the male's
      behavior is influenced by the "environment" of his mating partner's preferences
      for the display, generating epistasis through indirect genetic effects. Moreover,
      bottlenecked lines had up to 800% of the heritability of the controls, suggesting
      "conversion" of additive genetic variance from nonadditive components. Second, we
      used line-cross assays on separate populations that had been selected for
      divergence in mating behavior to identify dominance and epistasis through
      heterosis and outbreeding depression in courtship. Finally, our literature review
      confirms the prevalence of such low heritabilities (i.e., a conservative mean of
      0.38) and nonadditive genetics in other behavioral repertoires (64% of the
      studies). We conclude that animal behavior is especially prone to the gamut of
      quantitative genetic complexities that can result in negative heritabilities,
      negative selection responses, inbreeding depression, conversion, heterosis, and
      outbreeding depression.

PMID- 18707478
TI  - Sex chromosomes and sexual selection in poeciliid fishes.
AB  - We propose that the evolution of female preferences can be strongly influenced by
      linkage of attractive male traits to the Y chromosome and female preferences to
      the X chromosome in male heterogametic species. Such linkage patterns are
      predicted by models of the evolution of sexually antagonistic genes. Subsequent
      recombination of attractive male characters from the Y to the X would create
      physical linkage between attractive male trait and preference. A literature
      survey shows that Y linkage of potentially sexually antagonistic traits is common
      in poeciliid fishes and other species with sex chromosomes that are not well
      differentiated, but may also occur in taxa with degenerate Y chromosomes. In the
      guppy, attractive male traits are primarily Y and X linked; a literature review
      of the inheritance of sex-limited attractive male characters suggests that 16 are
      Y linked, 24 recombine between the X and Y, two are X linked, and two are
      autosomal. Crosses and backcrosses between high female preference (Endler's live
      bearers) and low female preference (Rio San Miguel) guppy populations show that
      this character has a strong additive genetic component and that it will be
      possible to investigate the physical linkage of male and female sexually selected
      characters in this species through mapping studies.

PMID- 18707480
TI  - Preface: behavior genetics for behavioral ecologists.

PMID- 18707479
TI  - An MHC component to kin recognition and mate choice in birds: predictions,
      progress, and prospects.
AB  - The major histocompatibility complex (Mhc) has been identified as a locus
      influencing disease resistance, mate choice, and kin recognition in mammals and
      fish. However, it is unclear whether the mechanisms by which Mhc genes influence
      behavior in mammals are applicable to other nonmammalian vertebrates such as
      birds. We review the biology of Mhc genes with particular reference to their
      relevance to avian mating and social systems. New genomics approaches recently
      have been applied to the Mhcs of chickens, quail, and several icons of avian
      behavioral ecology, including red-winged blackbirds (Agelaius phoeniceus) and
      house finches (Carpodacus mexicanus). The predominance of concerted evolution at
      avian Mhc loci makes such methods attractive for providing access to this
      complicated multigene family. Although some biological processes influenced by
      Mhc in mammals are physiologically implausible for birds, Mhc could influence
      cues that form well-known bases for mate choice in birds by influencing the
      health and vigor of individuals. The tight associations of Mhc variation and
      disease resistance in chickens raise hope that finding associations of Mhc genes,
      disease, and mate choice in natural populations of birds will be as fruitful as
      in mammalian systems.

PMID- 18707482
TI  - Testing the hypothesis that a clade has adaptively radiated: iguanid lizard
      clades as a case study.
AB  - The study of adaptive radiations has played a fundamental role in understanding
      mechanisms of evolution. A recent resurgence in the study of adaptive radiations
      highlights a gap in our knowledge about determining whether a clade constitutes
      adaptive diversification. Specifically, no objective criteria exist to judge
      whether a clade constitutes an adaptive radiation. Most clades, given enough
      time, will diversify adaptively to some extent; therefore, we argue that the term
      "adaptive radiation" should be reserved for those clades that are exceptionally
      diverse in terms of the range of habitats occupied and attendant morphological
      adaptations. Making such a definition operational, however, requires a
      comparative analysis of many clades. Only by comparing clades can one distinguish
      those that are exceptionally diverse (or nondiverse) from those exhibiting a
      normal degree of adaptive disparity. We propose such a test, focusing on
      disparity in the ecological morphology of monophyletic groups within the lizard
      family Iguanidae. We find that two clades, the Polychrotinae and Phrynosomatinae,
      are exceptionally diverse and that two others, the Crotaphytinae and Oplurinae,
      are exceptionally nondiverse. Potential explanations for differences in diversity
      are discussed, as are caveats and future extensions of our approach.

PMID- 18707483
TI  - Feeding under predation hazard: testing models of adaptive behavior with stream
      fish.
AB  - Many empirical studies support the premise that animals consider both the
      benefits of feeding and the cost of mortality when making behavioral decisions,
      and many theoretical studies predict animal behavior in the presence of a feeding
      mortality trade-off. However, empirical work is lacking in studies that
      quantitatively assess alternative models. Using data from two sets of behavioral
      experiments examining stream minnows (bluehead chubs) foraging in the presence of
      sunfish predators (green sunfish), we assess, via statistical model fitting, the
      utility of four basic optimization models of foraging behavior. Our analysis of
      feeding and mortality of the minnows indicates that mortality is incurred so as
      to feed above maintenance requirements, that feeding rate is suppressed in
      response to the presence of predators, and that the balance of feeding against
      mortality can be estimated using a life-history parameter theta, interpreted
      theoretically as the marginal rate of substitution of mortality rate for growth
      rate. Our results indicate that both body size and age are probably involved in
      determining the value of theta, and we suggest that future studies should focus
      on estimating and understanding this parameter.

PMID- 18707484
TI  - A unifying framework for metapopulation dynamics.
AB  - Many biologically important processes, such as genetic differentiation, the
      spread of disease, and population stability, are affected by the (natural or
      enforced) subdivision of populations into networks of smaller, partly isolated,
      subunits. Such "metapopulations" can have extremely complex dynamics. We present
      a new general model that uses only two functions to capture, at the
      metapopulation scale, the main behavior of metapopulations. We show how complex,
      structured metapopulation models can be translated into our generalized
      framework. The metapopulation dynamics arising from some important biological
      processes are illustrated: the rescue effect, the Allee effect, and what we term
      the "antirescue effect." The antirescue effect captures instances where high
      migration rates are deleterious to population persistence, a phenomenon that has
      been largely ignored in metapopulation conservation theory. Management regimes
      that ignore a significant antirescue effect will be inadequate and may actually
      increase extinction risk. Further, consequences of territoriality and conspecific
      attraction on metapopulation-level dynamics are investigated. The new, simplified
      framework can incorporate knowledge from epidemiology, genetics, and population
      biology in a phenomenological way. It opens up new possibilities to identify and
      analyze the factors that are important for the evolution and persistence of the
      many spatially subdivided species.

PMID- 18707485
TI  - Temporal variation in fitness payoffs promotes cooperative breeding in long
      tailed tits Aegithalos caudatus.
AB  - Cooperative breeding is paradoxical because some individuals forego independent
      reproduction and instead help others to reproduce. The ecological constraints
      model states that such behavior arises because of constraints on independent
      reproduction. Spatial variation in constraints has been shown to co-vary with the
      incidence of cooperative breeding in correlational and experimental studies.
      Here, we examine whether temporally variable ecological constraints can act in a
      similar way to promote cooperative breeding in the atypical system of long-tailed
      tits Aegithalos caudatus. In this species, individuals may switch reproductive
      tactics from breeding to helping within the same breeding season. Using 7 yr of
      field data, we show that reproductive success declined seasonally because of
      declines in brood size, nestling weight, and juvenile survival. The survival to
      breeding age of chicks from nests with helpers was higher than for chicks from
      nests without helpers, and since helpers usually helped at the nest of a close
      relative, they accrued inclusive fitness benefits. We used these data to model
      the expected fitness payoffs of breeding and helping at different times during
      the season. The model shows that late in the breeding season, the fitness payoff
      from a kin-directed helping tactic becomes greater than that from independent
      breeding. The behavioral switch predicted by the model is consistent with the
      observed switch from breeding to helping, which shows that cooperative breeding
      may evolve as a way of making the best of a bad job at the end of a temporally
      constrained breeding season.

PMID- 18707486
TI  - The effective size of annual plant populations: the interaction of a seed bank
      with fluctuating population size in maintaining genetic variation.
AB  - Many annual plant populations undergo dramatic fluctuations in size. Such
      fluctuations can result in the loss of genetic variability. Here I formalize the
      potential for a seed bank to buffer against such genetic loss. The average time
      to seed germination (T) defines the generation time of "annuals" with a seed
      bank, and assuming random seed germination, I show that, under otherwise ideal
      conditions, a population's effective size (Ne) equals NT, where N is the number
      of adult plants. This result supports the general principle that lengthening the
      prereproductive period increases Ne. When adult numbers vary, Ne at any time
      depends on N and on the numbers contributing to the seed bank in previous
      seasons. Averaging these effects over time gives Ne approximately Nh + (T - 1)Na,
      where Nh and Na are the harmonic and arithmetic means of the adult population.
      Thus if T >> 1, Ne is determined primarily by Na. Simulations showed that until
      fluctuations in N are large (>25x) this relationship is accurate. I extended the
      theory to incorporate a selfing rate (S) and reproductive variance (I) through
      seed production (k), outcrossed pollen (m), and variation in selfing rate: Ne =
      NT(1 -S/2)/(1 + I) = NT/[1 + FIS)(1 + I)]. Reproductive variance (I) equals [Ik(1
      + S)2 + IM(1 - S)2 + 2(1 - S2)Ikm = S2IS(1 + Ik)]/4, , where Ij is the
      standardized variance (Vj/j2) of factor j and Ikm is the standardized covariance
      between k and m. These results are applicable to other organisms with a similar
      life history, such as freshwater crustaceans with diapausing eggs (e.g., tadpole
      shrimp, clam shrimp, and fairy shrimp) and other semelparous species with
      discrete breeding seasons and a variable maturation time (e.g., Pacific salmon).

PMID- 18707487
TI  - A mechanism for the evolution of altruism among nonkin: positive assortment
      through environmental feedback.
AB  - The evolution of altruism often requires genetic similarity among interactors.
      For structured populations in which a social trait affects all group members,
      this entails positive assortment, meaning that cooperators and noncooperators
      tend to be segregated into different groups. Several authors have claimed that
      mechanisms other than common descent can produce positive assortment, but this
      claim has not been generally accepted. Here, we describe one such mechanism. The
      process of "environmental feedback" requires only that the cooperative trait
      affects the quality of the local environment and that individuals are more likely
      to leave low-quality than high-quality environments. We illustrate this dynamic
      using an agent-based spatial model of feeding restraint. Depending on parameter
      settings, results included both positive assortment (required for the evolution
      of altruism) and negative assortment (required for the evolution of spite). The
      mechanism of environmental feedback appears to be a general one that could play a
      role in the evolution of many forms of cooperation.

PMID- 18707488
TI  - Habitat selection by two competing species in a two-habitat environment.
AB  - We present a theoretical study of habitat selection strategies for two species
      that compete in an environment consisting of two different habitats. Our fitness
      functions are derived from the Lotka-Volterra competition equations, and we
      assume that individuals settle in the habitat in which their fitness is
      maximized. We derive an ideal free distribution across the habitats for both
      species. Our model provides analytical and graphical descriptions of individual
      habitat selection behavior, isolegs (the boundary lines separating regions where
      qualitatively different habitat preferences are predicted), and spatial
      population distributions. Our analysis reveals complex isolegs, several novel
      patterns of habitat distribution, and even situations where spatial strategies,
      as well as the relative abundances of coexisting species, exhibit only local
      stability. Hence, distributions of competing species may be determined not solely
      by their respective densities but also by the order of colonization. This
      happens, however, only for extreme levels of interspecific competition. In the
      situation where one competitor species is dominant over the other, our model
      predicts isolegs that qualitatively agree with observed behavioral patterns.
      However, our model predicts a greater variety of possible situations than has
      been previously described. Finally, we analyze the influence of habitat selection
      behavior on species isoclines and verify that increasing interspecific
      competition leads to habitat segregation.

PMID- 18707489
TI  - A model for evolution of male parental care and female multiple mating.
AB  - In most animals, males gain a fitness benefit by mating with many females,
      whereas the number of progeny per female is unlikely to increase as a function of
      additional mates. Furthermore, males of internally fertilizing species run the
      risk of investing in offspring of other males if they provide parental care.
      Nevertheless, males of many avian species and a minority of mammalian species
      provide parental care, and females of various species mate with multiple males. I
      investigate a two-locus genetic model for evolution of male parental care and
      female multiple mating in which females gain a direct benefit by multiple mating
      from the paternal care they thereby elicit for their offspring. The model
      suggests that, first, male parental care can evolve when it strongly enhances
      offspring survival and the direct costs of female multiple mating (e.g., loss of
      energy, risk of injury, exposure to infectious diseases) are greater than its
      indirect benefit (e.g., acquisition of good genes, increased genetic diversity
      among offspring); second, female multiple mating can evolve when paternal care is
      important for offspring survival or the indirect benefit of multiple mating is
      larger than its direct cost; and, finally, male parental care and female multiple
      mating can co-occur.

PMID- 18707490
TI  - Host-parasitoid association and diffuse coevolution: when to be a generalist?
AB  - In host-parasitoid communities, hosts are subjected to selective pressures from
      numerous parasitoid species, and parasitoids may attack several host species. The
      specificity of host resistance and parasitoid virulence is thus a key factor in
      host-parasitoid coevolution. A continuum of strategies exists, from strict
      specificity to a generalist strategy. The optimal level of specificity may differ
      in host and parasitoid. I investigated the optimal level of resistance
      specificity using a model in which the host could be attacked by two parasitoid
      species, with variable levels of defense specificity. The fitness of a parasitoid
      attacking two host species with different levels of virulence specificity was
      also modeled. Finally, a fluctuating environment was simulated by introducing
      variable probabilities of encounters between antagonistic species over several
      generations. If the frequency of encounters with the antagonistic species is
      fixed, then both host and parasitoid gain from a strategy of exclusive
      specialization toward the most frequent antagonist. If the frequency of
      encounters fluctuates between generations, generalist host resistance and
      partially specialist parasitoid virulence are favored. Generalist host resistance
      may be considered to be a bet-hedging response to an unpredictable environment.
      This asymmetry in host-parasitoid coevolution may account for some of the genetic
      structures observed in the field for host-parasitoid associations.

PMID- 18707491
TI  - To freeze or not to freeze? An evolutionary perspective on the cold-hardiness
      strategies of overwintering ectotherms.
AB  - We address the question of whether freeze-tolerance, freeze-avoidance, or mixed
      strategy represents the best adaptation for overwintering ectotherms to endure
      severe winter. To this end, we develop an optimization fitness model that takes
      into account different physiological parameters such as energetic level, the
      physiological stress associated with each strategy, and climatic variables. The
      results show that the freeze-tolerance strategy is strongly dependent on a low
      sensitivity to the number of freezing days and on a capacity to reduce stress
      associated with freezing. This strategy is also favored when the initial
      energetic level is low compared to the freeze-avoidance strategy, which is
      favored by a high initial energetic level, a low stress associated with the
      supercooling, and a low sensitivity of this strategy to climatic conditions. From
      a theoretical point of view, the mixed strategy permits survival in harsher
      environments but requires the optimization of all parameters involved in both
      cold-hardiness strategies. However, the mixed strategy shows energetic advantages
      in variable environments allowing animals to resist the harshest periods. From
      the model results, it appears that the physiological processes developed by
      ectotherms to reduce these stresses might be a key to understanding the evolution
      of the cold-hardiness strategies.

PMID- 18707492
TI  - Metapopulation structure favors plasticity over local adaptation.
AB  - We describe a model for the evolutionary consequences of plasticity in an
      environmentally heterogeneous metapopulation in which specialists for each of two
      alternative environments and one plastic type are initially present. The model is
      similar to that proposed by Moran (1992) but extends her work to two sites. We
      show that with migration between sites the plastic type is favored over local
      specialists across a broad range of parameter space. The plastic type may
      dominate or be fixed even in an environmentally uniform site, and even if the
      plasticity has imperfect accuracy or bears some cost such that a local specialist
      has higher fitness in that site, as long as there is some migration between sites
      with different distributions of environmental states. These results suggest that
      differences among taxa in dispersal and hence realized migration rates may play a
      heretofore unrecognized role in their patterns of adaptive population
      differentiation. Migration relaxes the thresholds for both environmental
      heterogeneity and accuracy of plastic response above which plasticity is favored.
      Furthermore, small changes in response accuracy can dramatically and abruptly
      alter the evolutionary outcome in the metapopulation. A fitness cost to
      plasticity will substantially reduce the range of conditions in which the plastic
      type will prevail only if the cost is both large and global rather than
      environment specific.

PMID- 18707495
TI  - Lack of premating isolation at the base of a phylogenetic tree.
AB  - Darwin's finches in the Galapagos archipelago are an unusual example of adaptive
      radiation in that the basal split separates two lineages of warbler finches
      (Certhidea olivacea and Certhidea fusca) believed until recently to be only one
      species. The large genetic difference between them contrasts with their
      similarity in plumage, size, shape, and courtship behavior. They differ in song,
      which is a key factor in premating isolation of other sympatric Darwin's finches.
      We conducted playback experiments to see whether members of the population of C.
      olivacea on Santa Cruz Island would respond to songs of C. fusca from two
      islands, Genovesa and Pinta, and songs of C. olivacea from another island
      (Isabela). Another set of experiments was performed, using the same playback
      tapes, with C. fusca on Genovesa. Some members of both populations responded to
      all playbacks; therefore, the hypothesis of complete premating isolation on the
      basis of song is rejected. Discrimination between songs of the two lineages was
      inconsistent. We conclude that premating barriers to interbreeding among the
      tested populations have not arisen in the 1.5-2.0 m.yr. of their geographical
      isolation on different islands. This contrasts with strong premating barriers
      between more recently derived sympatric species. Early learning of song
      associated with morphology is later used in mate recognition. This explains why
      sympatric species that are vocally and morphologically distinct yet genetically
      less differentiated than Certhidea do not interbreed, whereas the Certhidea
      lineages that are genetically well differentiated but vocally and morphologically
      similar have no apparent premating barrier. We discuss this unusual situation in
      terms of the forces that have produced similarities and differences in song,
      morphology, and ecology and their relevance to phylogenetic and biological
      species concepts. Neither principles nor details are unique to Darwin's finches,
      and we conclude by pointing out strong parallels with some continental birds.

PMID- 18707496
TI  - Comparing the consequences of induced and constitutive plant resistance for
      herbivore population dynamics.
AB  - Although it has been suggested that induced and constitutive plant resistance
      should have different effects on insect herbivore population dynamics, there is
      little experimental evidence that plant resistance can influence herbivore
      populations longer than one season. We used a density-manipulation experiment and
      model fitting to examine the effects of constitutive and induced resistance on
      herbivore dynamics over both the short and long term. We used likelihood methods
      to fit population dynamic models to recruitment data for populations of Mexican
      bean beetles on soybean varieties with no resistance, constitutive resistance, or
      induced resistance. We compared model configurations that fit parameters for
      resistance types separately to models that did not account for resistance type.
      Models representing the hypothesis that the three resistance types differed in
      their effects on beetle dynamics received the most support. Induced resistance
      resulted in lower population growth rates and stronger density dependence than no
      resistance. Constitutive resistance resulted in lower population growth rates and
      stronger density dependence than induced resistance. Constitutive resistance had
      a stronger effect on both short-term beetle recruitment and predicted beetle
      population dynamics than induced resistance. The results of this study suggest
      that induced and constitutive resistance can differ in their effects on herbivore
      populations even in a relatively complex system.

PMID- 18707497
TI  - Altruism, cheating, and anticheater adaptations in cellular slime molds.
AB  - Cellular slime molds (CSMs) possess a remarkable life cycle that encompasses an
      extreme act of altruism. CSM cells live as individual amoebae until starved, then
      aggregate and ultimately transform themselves into a multicellular fruiting body.
      This fruiting body consists of stalk cells (altruists that eventually die) and
      spores (the beneficiaries of this sacrifice). Altruistic systems such as this are
      vulnerable to cheaters, which are individuals unrelated to the altruists that
      obtain the benefits provided by them without reciprocating. Here, we investigate
      two forces that can maintain CSM altruism despite cheating: kin selection and
      anticheater adaptations. First, we present new kinship-based models based on CSM
      developmental biology to evaluate the efficacy of kin selection. These models
      show that stalk-making genotypes can still be maintained when aggregations are
      initiated by multiple "founder" spores, provided that spores of stalkless
      fruiting bodies have low rates of dispersal and dispersal success is a concave
      function of stalk height. Second, we review proposals that several features of
      CSM development, such as the chemical suppression of the redifferentiation of
      prestalk cells into prespores, act as anticheater adaptations.

PMID- 18707498
TI  - Snow tussocks, chaos, and the evolution of mast seeding.
AB  - One hitherto intractable problem in studying mast seeding (synchronous
      intermittent heavy flowering by a population of perennial plants) is determining
      the relative roles of weather, plant reserves, and evolutionary selective
      pressures such as predator satiation. We parameterize a mechanistic resource
      based model for mast seeding in Chionochloa pallens (Poaceae) using a long-term
      individually structured data set. Each plant's energy reserves were reconstructed
      using annual inputs (growing degree days), outputs (flowering), and a novel
      regression technique. This allowed the estimation of the parameters that control
      internal plant resource dynamics, and thereby allowed different models for
      masting to be tested against each other. Models based only on plant size, season
      degree days, and/or climatic cues (warm January temperatures) fail to reproduce
      the pattern of autocovariation in individual flowering and the high levels of
      flowering synchrony seen in the field. This shows that resource-matching or
      simple cue-based models cannot account for this example of mast seeding. In
      contrast, the resource-based model pulsed by a simple climate cue accurately
      describes both individual-level and population-level aspects of the data. The
      fitted resource-based model, in the absence of environmental forcing, has chaotic
      (but often statistically periodic) dynamics. Environmental forcing synchronizes
      individual reproduction, and the models predict highly variable seed production
      in close agreement with the data. An evolutionary model shows that the chaotic
      internal resource dynamics, as predicted by the fitted model, is selectively
      advantageous provided that adult mortality is low and seeds survive for more than
      1 yr, both of which are true for C. pallens. Highly variable masting and chaotic
      dynamics appear to be advantageous in this case because they reduce seed losses
      to specialist seed predators, while balancing the costs of missed reproductive
      events.

PMID- 18707499
TI  - Analyzing spatial structure of communities using the two-dimensional poisson
      lognormal species abundance model.
AB  - The joint spatial and temporal fluctuations in the community structure of
      tropical butterflies are analyzed by fitting the bivariate Poisson lognormal
      distribution to a large number of observations in space and time. By applying
      multivariate dependent diffusions for describing the fluctuations in the
      abundances, the environmental variance is estimated to be very large and so is
      the strength of local density regulation. The variance in the lognormal species
      abundance distribution is partitioned into components expressing the
      heterogeneity between the species, independent noise components for the different
      species, a demographic stochastic component, and a component due to
      overdispersion in the sampling. In disagreement with the neutral theory, the
      estimates show that the heterogeneity component is the dominating one,
      representing 81% of the total variance in the lognormal model. Different spatial
      components of diversity, the alpha, beta, and gamma diversity, are also
      estimated. The spatial scale of the autocorrelation function for the community is
      of order 1 km, while sampling of a quadrat would need to be 10 km on a side to
      yield the total diversity for the community.

PMID- 18707500
TI  - Extinction and introgression in a community of partially cross-fertile plant
      species.
AB  - We develop a model to study the demography and genetics of an encounter between
      two partially cross-fertile plant species. We assume prezygotic reproductive
      isolation between the species, a common situation when the species differ by
      their phenology or floral traits that cause assortative mating. Three outcomes
      are possible: coexistence of both species with minimal introgression; domination
      by one species, with the other becoming extinct or surviving only through
      recurrent migration; or domination of the community by hybrid derivatives, with
      both species surviving but with a rather high level of introgression between
      them. The first situation is reached when interfertility is low, while the third
      requires high interfertility to develop. Occurrence of the second situation is
      observed with intermediate values of interfertility. Gene flow from nearby
      monospecific populations can prevent both introgression and the domination of the
      community by one species. Conversely, increasing the number of loci that
      determine the reproductive isolation between species or decreasing the degree of
      nonadditive interactions (epistasis and/or dominance) between alleles and loci
      makes introgression more likely. We found that hybridization can create positive
      frequency dependence and make extinction possible, even when hybrid individuals
      have no intrinsic fitness advantage.

PMID- 18707501
TI  - A comparative test of the adaptive plasticity hypothesis: relationships between
      habitat and phenotype in anuran larvae.
AB  - The hypothesis that phenotypic plasticity is maintained by divergent natural
      selection acting across different environments predicts that populations and
      species exposed to highly variable environments will express high levels of
      plasticity. I tested this prediction by measuring the behavioral and
      morphological responses to aeshnid dragonfly larvae of 16 tadpole species and
      asking whether predator-induced plasticity is greater in species that experience
      more variable densities of predators in nature. Tadpole phenotypes were measured
      in a series of similar experiments in outdoor artificial ponds carried out over a
      9-yr period. I quantified tadpole habitats by soliciting evaluations by seven to
      36 experienced field observers for each species. There were large differences
      among species in phenotype, mostly in agreement with earlier descriptions. Nearly
      all species responded to dragonflies by decreasing activity and body length
      relative to overall body size and by increasing relative tail fin depth, although
      the magnitude of the responses differed among species. There was a significant
      positive phylogenetic correlation between morphological plasticity and
      variability in exposure to predators, thus upholding the adaptive hypothesis. The
      correlation between behavioral responses and habitat variability was not
      significant, and there was little relationship between behavioral and
      morphological plasticity, raising the possibility that behavioral responses
      evolve under different scales of environmental variation than morphological
      responses.

PMID- 18707502
TI  - Sex ratios and skew models: the special case of evolution of cooperation in
      polistine wasps.
AB  - Cooperative breeding often involves reproductive dominance hierarchies. Such
      hierarchies have been proposed to form and to be maintained through an equitable
      skew in reproduction for both dominants and subordinates. The general form of
      skew models also predicts that cooperation can be stable only if cooperation
      greatly increases group reproductive success or subordinates are greatly
      constrained in their reproductive prospects relative to dominants. Neither,
      however, seems to be generally present in the colony initiation phase of
      temperate polistine wasps, although the behaviors of individuals within such
      groups are often consistent with skew model predictions. This apparent
      contradiction can be resolved in the context of a special case of the skew models
      that incorporate mother-offspring conflicts over sex ratios. Data suggest that
      all the needed preconditions are present for cooperating foundresses to gain an
      added benefit through producing male-biased investment ratios. Therefore, the
      special case model predicts that cooperation can evolve in Hymenoptera with both
      the observed high skews and reduced per capita group productivity. Further
      predictions of the special case model (e.g., mixed populations of single and
      multifoundresses) are also supported. Because the special case model is
      applicable only to haplodiploids, this may explain why cooperation in vertebrates
      rarely occurs without significant ecological or physiological constraints.
      Finally, comparisons to other social Hymenoptera taxa suggest that factors
      stabilizing cooperation between colony-initiating females may simultaneously
      constrain the evolution of morphologically specialized worker castes.

PMID- 18707503
TI  - Predator-prey dynamics and movement in fractal environments.
AB  - Previous research suggests that local interactions and limited animal mobility
      can affect population dynamics. However, the spatial structure of the environment
      can further limit the mobility of animals. For example, an animal confined to a
      river valley or to a particular plant cannot move with equal ease in all
      directions. We show that spatial architecture could influence the population
      dynamics of predator-prey systems using individual-based computer simulations
      parameterized with allometric relationships from the literature. Spatial forms
      (representing geographical features or plant architecture) of differing fractal
      dimension were generated, and simulated predators and prey were introduced into
      these computer environments. We claim that the alteration in interaction rates
      and population dynamics found in these simulations can be explained as a
      consequence of the anomalously slow rates of movement associated with fractal
      spaces and the diffusion-limited nature of predator-prey interactions. As a
      result, functional responses and numerical responses are substantially reduced in
      fractal environments, and the overall stability of the system is determined by
      the interaction between individual mobility and spatial architecture.

PMID- 18707504
TI  - The division of labor: genotypic versus phenotypic specialization.
AB  - A model of the division of labor in simple evolving systems is explored to
      compare two strategies evident in natural populations: phenotypic specialization
      (such as differentiation by regulated gene expression) and genotypic
      specialization (such as co-infection by complementary covirus populations). While
      genotypic specialization is vulnerable to the chance extinction of an essential
      specialist type and to parasitism, phenotypic specialization is able to overcome
      these hurdles. When simple spatial effects are included, phenotypic
      specialization has further benefits, protecting against destructive dynamic
      patterns. Many of the advantages of phenotypic specialization, however, can only
      be realized when a high degree of relatedness within groups is ensured.

PMID- 18707506
TI  - Evolutionary dynamics of intron size, genome size, and physiological correlates
      in archosaurs.
AB  - It has been proposed that intron and genome sizes in birds are reduced in
      comparison with mammals because of the metabolic demands of flight. To test this
      hypothesis, we examined the sizes of 14 introns in a nonflying relative of birds,
      the American alligator (Alligator mississippiensis), and in 19 flighted and
      flightless birds in 12 taxonomic orders. Our results indicate that a substantial
      fraction (66%) of the reduction in intron size as well as in genome size had
      already occurred in nonflying archosaurs. Using phylogenetically independent
      contrasts, we found that the proposed inverse correlation of genome size and
      basal metabolic rate (BMR) is significant among amniotes and archosaurs, whereas
      intron and genome size variation within birds showed no significant correlation
      with BMR. We show statistically that the distribution of genome sizes in birds
      and mammals is underdispersed compared with the Brownian motion model and
      consistent with strong stabilizing selection; that genome size differences
      between vertebrate clades are overdispersed and punctuational; and that evolution
      of BMR and avian intron size is consistent with Brownian motion. These results
      suggest that the contrast between genome size/BMR and intron size/BMR
      correlations may be a consequence of different intensities of selection for these
      traits and that we should not expect changes in intron size to be significantly
      associated with metabolically costly behaviors such as flight.

PMID- 18707507
TI  - Plant community dynamics, nutrient cycling, and alternative stable equilibria in
      peatlands.
AB  - Although observational data and experiments suggest that carbon flux and storage
      in peatlands are controlled by hydrology and/or nutrient availability, we lack a
      rigorous theory to account for the roles that different plant species or life
      forms, particularly mosses, play in carbon and nutrient flux and storage and how
      they interact with different hydrologic sources of nutrients. We construct and
      analyze a model of peatlands that sheds some light on this problem. The model is
      a set of six coupled differential equations that define the flow of nutrients
      from moss and vascular plants to their litters, then to peat, and finally to an
      inorganic nutrient resource pool. We first analyze a simple version of this model
      (model 1) in which all nutrient input is from precipitation and enters the moss
      compartment directly, mimicking the dynamics of ombrotrophic bogs. There is a
      transcritical bifurcation that results in a switch of stability between two
      equilibrium bog communities: a moss monoculture and a community where mosses and
      vascular plants coexist. The bifurcation depends on the magnitudes of the
      input/output budget of the peatland and the life-history traits of the plants. We
      generalize model 1 to model 2 by dividing nutrient inputs between precipitation
      and groundwater, thus also allowing the development of minerotrophic fens that
      receive nutrient subsidies from both groundwater and precipitation and adding
      intraspecific competition (self-limitation) terms for both moss and vascular
      plants. Partitioning precipitation inputs between moss and the nutrient pool
      resulted in the greatest changes in model behavior, including the appearance of a
      lake and a vascular plant monoculture as well as the moss monoculture and
      coexistence equilibrium. As with model 1, these solutions are separated by
      transcritical bifurcations depending on critical combinations of parameters
      determining the input-output budget of the peatland as well as the life-history
      characteristics of the plant species. Model 2 also allowed for an early transient
      spike in vascular plant dominance followed by approach to near moss monoculture
      and then eventual approach to coexistence equilibrium. This generalized model
      mimics the broad features of successional development of peatlands from fens to
      bogs often found in the paleorecords of peat cores.

PMID- 18707508
TI  - Experimental adaptive radiation in Pseudomonas.
AB  - We studied the importance of selection and constraint in determining the limits
      of adaptive radiation and the consequences of adaptive radiation in an
      experimental system. We propagated four replicate lines of the bacterium
      Pseudomonas fluorescens derived from a single ancestral clone in 95 environments,
      where growth was limited by the availability of a single carbon source for 1,000
      generations. We then assayed the growth of the ancestral clone and the evolved
      lines in all 95 environments. Evolved lines increased their performance in almost
      every selection environment and invaded 70% of the novel environments as a direct
      response to selection. Direct responses tended to be larger in environments where
      growth was initially poor. Although evolved lines lost the ability to grow on
      about three substrates that their ancestor could readily grow on, the correlated
      response to selection was, on average, positive. The correlated response allowed
      all of our evolved populations to expand their niches and to occupy collectively
      the remaining novel habitats. This is inconsistent with classical theories of
      niche evolution. In the most extreme cases, adaptation occurred through
      "roundabout selection": lineages became adapted to an environment through
      selection in another environment but not through selection in the environment
      itself. Our results indicate that mutation accumulation by neutral drift was
      responsible for generating the majority of costs of adaptation.

PMID- 18707509
TI  - Reconstructing an adaptationist scenario: what selective forces favor the
      evolution of viviparity in montane reptiles?
AB  - It is notoriously difficult to test hypotheses about the selective forces
      responsible for major phylogenetic transitions in life-history traits, but the
      evolution of viviparity (live bearing) in reptiles offers an ideal model system.
      Viviparity has arisen in many oviparous reptile lineages that have invaded colder
      climates. Thermal advantages (eggs retained within the mother's body will be
      warmer than those laid in the nest) are almost certainly important, but the
      actual selective pressures remain controversial. For example, the benefit to
      retention might involve faster development, protection against freezing,
      predation, or desiccation, or modification of hatchling phenotypes. I
      experimentally manipulated incubation regimes of a montane scincid lizard
      (Bassiana duperreyi, Scincidae) to test these ideas. Eggs maintained in cooler
      "nests" in the laboratory developed more slowly, were more likely to die before
      hatching, and produced inferior (small, slow) hatchlings. A 2-wk initial period
      of higher-temperature incubation (simulating uterine retention, an intermediate
      step toward viviparity) ameliorated these effects. In the field, I placed eggs in
      artificial nests at the upper elevational limit of natural nests and also
      extending a further 100 m higher on the mountain. The results mirrored those in
      the laboratory: retention at maternal body temperatures accelerated hatching,
      enhanced hatching success, and increased locomotor speeds of hatchlings. This
      selective advantage of uterine retention was greater at higher elevations and
      increased with longer retention. The causal process responsible was prolonged low
      temperature incubation rather than freezing, desiccation, or predation, and both
      hatching success and hatchling viability were affected. Field experiments that
      directly re-create selective regimes may thus provide robust tests of
      adaptationist hypotheses.

PMID- 18707510
TI  - Sensory trap as the mechanism of sexual selection in a damselfly genitalic trait
      (Insecta: Calopterygidae).
AB  - During copulation, males of some calopterygid damselfly species displace the
      sperm stored in the spermatheca: the male genital appendages enter into the
      spermathecal ducts and physically remove sperm. In Calopteryx haemorrhoidalis,
      the genital appendages are too wide to penetrate the spermathecae, but males use
      a different mechanism in which the aedeagus stimulates the vaginal sensilla that
      control spermathecal sperm release. Since these sensilla are used during egg
      fertilization and oviposition, it was hypothesized that this function evolved
      before the male stimulatory ability. I investigated this using Hetaerina
      cruentata, a species whose position in the Calopterygidae phylogeny is more basal
      than Calopteryx. Given this position and having determined that males of this
      species are not able to displace sperm of their conspecific females during
      copulation, it was expected that H. cruentata females would eject sperm when
      stimulated with the aedeagi of C. haemorrhoidalis but not when stimulated with
      the aedeagi of their conspecifics. This prediction was confirmed. In order to
      investigate the widespread nature of this result, some other Calopteryx species
      Calopteryx xanthostoma and Calopteryx virgo-were investigated. The results were
      similar to those of H. cruentata: conspecific males were unable to stimulate
      their females, but females ejected sperm when stimulated with C. haemorrhoidalis
      aedeagi. Morphometric analysis suggests that the mechanistic explanation for the
      stimulatory ability of C. haemorrhoidalis genitalia is that the aedeagal region
      that makes contact with the vaginal sensilla is wider in C. haemorrhoidalis than
      in the other species. These results suggest that the sensory "bias" shown and
      shared by H. cruentata, Calopteryx splendens, C. virgo, and C. haemorrhoidalis
      females represents an ancestral condition and that the male stimulatory ability
      is absent in the evolutionary history of the clade. These pieces of evidence as
      well as another one presented elsewhere, which indicates that C. haemorrhoidalis
      males vary in their stimulatory ability, constitute the three criteria for a case
      of sexual selection via exploitation of a female sensory bias. These results also
      provide support to the sensory trap hypothesis that indicates that the female
      bias-in this case, egg fertilization and oviposition-evolved in a context
      different from sexual selection. Considering that the male genital appendages
      responsible for physically removing spermathecal sperm in other calopterygids are
      present in C. haemorrhoidalis, I suggest that males were once able to displace
      spermathecal sperm physically. Such ability may have been later impeded by a
      reduction in size of the spermathecal ducts. Possibly, one of the latest events
      in this sequence is the male's stimulatory ability. This hypothetical series of
      events suggests a coevolutionary scenario in which the central actor is the sperm
      stored in the spermathecae.

PMID- 18707511
TI  - Female control of the distribution of paternity in cooperative breeders.
AB  - Models of reproductive skew have shed light on why animal societies vary in the
      partitioning of reproduction among group members. However, their application to
      cooperative vertebrate societies remains controversial. A particular problem is
      that previous models assume that skew in paternity is determined by interactions
      among males and males only. This conflicts with observations from many species
      that indicate that females exert control over the distribution of paternity. Here
      we address this shortfall in the current theory by developing two models to
      explore the expected patterns of skew in three member groups in which a female
      controls the allocation of paternity among two males. The first "staying
      incentive" model extends previous "transactional" (or "concession") models to
      examine the conditions where females will be willing to share reproduction among
      a dominant and a subordinate male to retain the subordinate in the group. The
      second "work incentive" model explores patterns of skew where females allocate
      paternity in order to maximize the amount of care their offspring receive. The
      models make contrasting predictions about the nature of male-female conflict over
      reproduction and also about the relationships between skew and relatedness,
      ecological constraints, the relative quality of the subordinate male, and the
      relative cost of care for the two males. These divergent predictions provide a
      schema by which the evolutionary causes of variation in skew among males can be
      evaluated.

PMID- 18707512
TI  - The effective size of a metapopulation living in a heterogeneous patch network.
AB  - I analyze stochastic patch occupancy models (SPOMs), which record habitat patches
      as empty or occupied. A problem with SPOMs has been that if the spatial structure
      of a heterogeneous habitat patch network is taken into account, the computational
      effort needed to analyze a SPOM grows as a power of 2n, where n is the number of
      habitat patches. I propose a computationally feasible approximation method, which
      approximates the behavior of a heterogeneous SPOM by an "ideal" metapopulation
      inhabiting a network of identical and equally connected habitat patches. The
      transformation to the ideal metapopulation is based on weighting the individual
      patch occupancies by the dynamic values of the habitat patches, which may be
      calculated from the deterministic mean-field approximation of the original SPOM.
      Conceptually, the method resembles the calculation of the effective size of a
      population in the context of population genetics. I demonstrate how the method
      may be applied to SPOMs with flexible structural assumptions and with spatially
      correlated and temporally varying parameter values. I apply the method to a real
      habitat patch network inhabited by the Glanville fritillary butterfly,
      illustrating that the metapopulation dynamics of this species are essentially
      driven by temporal variability in the environmental conditions.

PMID- 18707513
TI  - Cluster analysis of spatial patterns in Malaysian tree species.
AB  - Tree species in tropical rain forests exhibit a rich panoply of spatial patterns
      that beg ecological explanation. The analysis of tropical census data typically
      relies on spatial statistics, which quantify the average aggregation tendency of
      a species. In this article we develop a cluster-based approach that complements
      traditional spatial statistics in the exploration and analysis of ecological
      hypotheses for spatial pattern. We apply this technique to six study species
      within a fully mapped 50-ha forest census in peninsular Malaysia. For each
      species we identify the scale(s) of spatial aggregation and the corresponding
      tree clusters. We study the correlation between cluster locations and abiotic
      variables such as topography. We find that the distribution of cluster sizes
      exhibits equilibrium and nonequilibrium behavior depending on species life
      history. The distribution of tree diameters within clusters also varies according
      to species life history. At different spatial scales, we find evidence for both
      niche-based and dispersal-limited processes producing spatial pattern. Our
      methodology for identifying scales of aggregation and clusters is general; we
      discuss the method's applicability to spatial problems outside of tropical plant
      ecology.

PMID- 18707514
TI  - Mate-search efficiency can determine the evolution of separate sexes and the
      stability of hermaphroditism in animals.
AB  - Limited availability of mating partners has been proposed as an explanation for
      the occurrence of simultaneous hermaphroditism in animals with pair mating. When
      low population density or low mobility of a species limits the number of
      potential mates, simultaneous hermaphrodites may have a selective advantage
      because, first, they are able to adjust the allocation of resources between male
      and female functions in order to maximize fitness; second, in a hermaphroditic
      population the likelihood of meeting a partner is higher because all individuals
      are potential mates; and, third, in the absence of mating partners, many
      simultaneously hermaphroditic animals have the option of reproducing through self
      fertilization. Recognizing that mate availability is central to the existing
      theory of hermaphroditism in animals, it is important to examine the effects of
      mate search on predictions of the stability of hermaphroditism. Many
      hermaphroditic animals can increase the number of potential mates they contact by
      active searching. However, since mate search has costs in terms of time and
      energy, the increased number of potential mates will be traded off against the
      amount of resources that can be allocated to the production of gametes. We
      explore the consequences of this trade-off to the evolution of mating strategies
      and to the selective advantage of self-fertilization. We show that in low and
      moderate population densities, poor mate-search efficiency and high costs of
      searching stabilize hermaphroditism and bias sex allocation toward female
      function. In addition, in very low population densities, there is strong
      selective advantage for self-fertilization, but this advantage decreases
      considerably in species with high mate-search efficiency. Most important,
      however, we present a novel evolutionary prediction: when mate search is
      efficient, disruptive frequency-dependent selection on time allocation to mate
      search leads to the evolution of searching and nonsearching phenotypes and,
      ultimately, to the evolution of males and females.

PMID- 18707515
TI  - On a genetic model of intraspecific competition and stabilizing selection.
AB  - A genetic model is investigated in which two recombining loci determine the
      genotypic value of a quantitative trait additively. Two opposing evolutionary
      forces are assumed to act: stabilizing selection on the trait, which favors
      genotypes with an intermediate phenotype, and intraspecific competition mediated
      by that trait, which favors genotypes whose effect on the trait deviates most
      from that of the prevailing genotypes. Accordingly, fitnesses of genotypes have a
      frequency-independent component describing stabilizing selection and a frequency-
      and density-dependent component modeling competition. We study how the underlying
      genetics, in particular recombination rate and relative magnitude of allelic
      effects, interact with the conflicting selective forces and derive the resulting,
      surprisingly complex equilibrium patterns. We also investigate the conditions
      under which disruptive selection on the phenotypes can be observed and examine
      how much genetic variation can be maintained in such a model. We discovered a
      number of unexpected phenomena. For instance, we found that with little
      recombination the degree of stably maintained polymorphism and the equilibrium
      genetic variance can decrease as the strength of competition increases relative
      to the strength of stabilizing selection. In addition, we found that mean fitness
      at the stable equilibria is usually much lower than the maximum possible mean
      fitness and often even lower than the fitness at other, unstable equilibria.
      Thus, the evolutionary dynamics in this system are almost always nonadaptive.

PMID- 18707516
TI  - Multiple receivers, multiple ornaments, and a trade-off between agonistic and
      epigamic signaling in a widowbird.
AB  - Sexual displays often involve several different ornamental traits. Yet most
      indicator models of sexual selection based on a single receiver (usually a choosy
      female) find that multiple handicap signals should be unstable. Here we study
      reasons for this contradiction, analyzing signal function, signal content, and
      trade-offs between signals in the polygynous red-collared widowbird Euplectes
      ardens. Males have both a long, graduated tail and a red carotenoid collar badge.
      Territory-holding "residents" have slightly shorter tails than the nonbreeding
      "floaters," but their carotenoid collars are 40% larger, and they have (on the
      basis of reflectance spectrometry and objective colorimetry) a 23-nm more long
      wave ("redder") hue than floaters. This corroborates experimental evidence that
      the red collar is selected by male contest competition, whereas female choice is
      based almost exclusively on male tail length. Tail length is negatively
      correlated with the carotenoid signal, which together with body size and
      condition explains 55% of the variation in tail length. The trade-off in tail
      length and carotenoid investment is steeper among residents, suggesting an
      interaction with costs of territory defense. We propose that the "multiple
      receiver hypothesis" can explain the coexistence of multiple handicap signals.
      Furthermore, the trade-off between signal expressions might contribute to the
      inverse relation between nuptial tail elongation and coloration in the genus
      Euplectes (bishops and widowbirds).

PMID- 18707517
TI  - The evolution of traits affecting resource acquisition and predator
      vulnerability: character displacement under real and apparent competition.
AB  - This article investigates some simple models of the evolutionary interaction
      between two prey species that share a common resource and a common predator. Each
      prey species is characterized by a trait that determines both the rate of
      resource capture and vulnerability to a predator. In a simple model of a three
      species food chain, such traits usually increase in response to an imposed
      reduction in resource density. When the per capita growth rates of each of two
      prey species depend linearly on resource density, such traits will change in
      opposite directions when the two prey come into sympatry. In addition, the ratio
      of the effect of the predator on prey fitness to the effect of the resource on
      prey fitness will diverge from the corresponding ratio in a second prey species
      when those species coexist in sympatry. These simple predictions need not hold
      under several alternative assumptions, which may be more common in biological
      systems. Parallel changes in sympatry may occur if the relationship between
      resource consumption and prey growth is nonlinear, if the prey species have
      partial overlap in the set of resources used or in the set of predators that
      consume them, or if prey experience direct intraspecific competition. The
      responses to a second prey can also differ significantly from those predicted by
      the simplest model if separate traits affect vulnerability to predators and
      resource acquisition rate. It is important to determine whether examples of
      character displacement previously interpreted as responses to competition for
      resources might also reflect responses to altered predation risks in sympatry.

PMID- 18707519
TI  - Ecological and genetic correlates of long-term population trends in the park
      grass experiment.
AB  - The Park Grass Experiment (PGE) is the longest-observed set of experimental plant
      communities in existence. Although the gross composition of the vegetation was at
      equilibrium over the 60-yr period from 1920 to 1979, annual records show that
      individual species exhibited a range of dynamics. We tested two hypotheses to
      explain why some species initially increased and why subsequently some of these
      (the outbreak species) decreased again. The study was designed around eight
      phylogenetically independent contrasts (PICs), each containing related species
      with different dynamics. Our first hypothesis was that persistent increasers and
      outbreakers have higher intrinsic rates of natural increase than control species
      (species without trends), allowing them to spread when interspecific competition
      is reduced by drought. This was tested by measuring establishment and seed
      production of species in field experiments, with and without interspecific
      competition. Seed production in outbreak species responded more strongly to
      release from interspecific competition than it did in either of the other groups
      of species. Our second hypothesis was that outbreak species eventually declined
      because they lacked the genetic variation necessary to adapt to the novel
      habitats to which they had initially spread. We tested this by measuring mating
      systems and genetic diversity in persistent and outbreak species in the PGE. In
      seven out of seven PICs tested, the outbreak species was more selfing than its
      persistent relative. There was a significant positive correlation between
      outcrossing rate and gene diversity. These results support roles for both
      ecological and genetic traits in long-term dynamics.

PMID- 18707520
TI  - The continuous prisoner's dilemma and the evolution of cooperation through
      reciprocal altruism with variable investment.
AB  - Understanding the evolutionary origin and persistence of cooperative behavior is
      a fundamental biological problem. The standard "prisoner's dilemma," which is the
      most widely adopted framework for studying the evolution of cooperation through
      reciprocal altruism between unrelated individuals, does not allow for varying
      degrees of cooperation. Here we study the continuous iterated prisoner's dilemma,
      in which cooperative investments can vary continuously in each round. This game
      has been previously considered for a class of reactive strategies in which
      current investments are based on the partner's previous investment. In the
      standard iterated prisoner's dilemma, such strategies are inferior to strategies
      that take into account both players' previous moves, as is exemplified by the
      evolutionary dominance of "Pavlov" over "tit for tat." Consequently, we extend
      the analysis of the continuous prisoner's dilemma to a class of strategies in
      which current investments depend on previous payoffs and, hence, on both players'
      previous investments. We show, both analytically and by simulation, that payoff
      based strategies, which embody the intuitively appealing idea that individuals
      invest more in cooperative interactions when they profit from these interactions,
      provide a natural explanation for the gradual evolution of cooperation from an
      initially noncooperative state and for the maintenance of cooperation thereafter.

PMID- 18707521
TI  - The spatial scale of population fluctuations and quasi-extinction risk.
AB  - Using a spatially homogeneous population model with migration (random individual
      dispersal) and spatially autocorrelated environmental noise, we show how
      migration and local density regulation affect the spatial scale of fluctuations
      in the log of population sizes as well as the 1-yr differences in these. The
      difference between the squares of these two spatial scales of population
      fluctuations does not depend on the spatial scale of the noise but only on
      migration rate and strength of local density regulation. We also show how
      migration, local density regulation, and spatially correlated environmental noise
      affect the realized population process at a specific location. As the migration
      increases, the realized local density regulation and the expected population size
      increase, while the realized environmental noise decreases. This approach also
      enables us to analyze the dynamics of the total population size within quadrats
      of different sizes. The risk of local quasi extinction is strongly reduced by
      increasing quadrat size or migration rate, while an increase in environmental
      stochasticity or spatial correlation in the environmental noise increases the
      risk of quasi extinction.

PMID- 18707522
TI  - Coexistence and relative abundance in annual plant assemblages: the roles of
      competition and colonization.
AB  - Although an interspecific trade-off between competitive and colonizing ability
      can permit multispecies coexistence, whether this mechanism controls the
      structure of natural systems remains unresolved. We used models to evaluate the
      hypothesized importance of this trade-off for explaining coexistence and relative
      abundance patterns in annual plant assemblages. In a nonspatial model,
      empirically derived competition-colonization trade-offs related to seed mass were
      insufficient to generate coexistence. This was unchanged by spatial structure or
      interspecific variation in the fraction of seeds dispersing globally. These
      results differ from those of the more generalized competition-colonization models
      because the latter assume completely asymmetric competition, an assumption that
      appears unrealistic considering existing data for annual systems. When, for
      heuristic purposes, completely asymmetric competition was incorporated into our
      models, unlimited coexistence was possible. However, in the resulting abundance
      patterns, the best competitors/poorest colonizers were the most abundant, the
      opposite of that observed in natural systems. By contrast, these natural patterns
      were produced by competition-colonization models where environmental
      heterogeneity permitted species coexistence. Thus, despite the failure of the
      simple competition-colonization trade-off to explain coexistence in annual plant
      systems, this trade-off may be essential to explaining relative abundance
      patterns when other processes permit coexistence.

PMID- 18707523
TI  - Delayed dispersal as a route to breeding: territorial inheritance, safe havens,
      and ecological constraints.
AB  - The relative roles of ecological constraints, the benefits of philopatry, and the
      role of life history continue to be debated in the evolution of natal philopatry
      and cooperative breeding. We compare three routes to breeding: departing to
      search for territories as a floater, staying and queuing to inherit the natal
      territory, or queuing and eventually shifting to a neighboring vacancy. Our model
      assumed a dominance-structured population. It quantifies the benefits of
      philopatry for varying-rank subordinates and contrasts it against the benefit of
      dispersal. We apply the model to data on Siberian jay Perisoreus infaustus, a
      species in which retained offspring do not help at the nest. The results indicate
      that territorial inheritance plays a small role in this species (presumably due
      to inbreeding avoidance), and territory acquisition is less constrained for
      dispersing than philopatric offspring. Nevertheless, small family groups-one or,
      at the most, two same-sex queuers-are predicted to form because philopatric
      offspring gain nepotistic benefits that improve their survival. This fits with
      data on group sizes and supports the idea of the natal territory as a safe haven
      for waiting for breeding opportunities. We also discuss our predictions in the
      light of ecological constraints and clarify recent confusingly different
      predictions on the role of habitat saturation as an explanation for delayed
      dispersal and cooperative breeding. We argue that "ecological constraint" is too
      wide a term to yield useful predictive power and that it is more appropriate to
      examine the consequences of specific life-history traits on the success of
      dispersers.

PMID- 18707524
TI  - Sexual conflict and polyspermy under sperm-limited conditions: in situ evidence
      from field simulations with the free-spawning marine echinoid Evechinus
      chloroticus.
AB  - For free-spawning organisms that release gametes into the sea, sperm limitation
      (too few sperm to fertilize all eggs) is a major factor limiting reproductive
      success. Given such circumstances, the presence of several mechanisms to prevent
      polyspermy (too many sperm) may seem paradoxical; however, a growing body of data
      suggests that natural fertilization levels, though variable, can routinely be
      high. Under such conditions, polyspermy is much more likely. The tension between
      sperm limitation and polyspermy represents sexual conflict because males, in
      competing to fertilize as many eggs as possible, can impose lethal costs on eggs
      if multiple sperm gain entry. Here we present data for a marine invertebrate
      indicating high levels of polyspermy under sperm-limited conditions. When the sea
      urchin Evechinus chloroticus was induced to spawn in situ, mean rates of
      polyspermy were [Formula: see text], and polyspermy was recorded at rates as high
      as 62.7%. Polyspermy was nearly always present, even when fertilization rates
      were <50%, confirming predictions that it should be present under sperm-limited
      conditions. Both sperm limitation and polyspermy imposed substantial reproductive
      costs, and we conclude that both sexual conflict related to polyspermy and sperm
      limitation have been simultaneous strong selective forces shaping the evolution
      of reproductive traits in the sea.

PMID- 18707525
TI  - Developmental rate isomorphy in insects and mites.
AB  - When the proportion of total developmental time spent in a particular
      developmental stage does not change with temperature, an organism shows "rate
      isomorphy." This is the case only if the lower developmental threshold is the
      same for all developmental stages. In this study, the incidence of rate isomorphy
      in seven species of mites and 342 species from 11 insect orders (some represented
      by several populations) was determined. Whether a species shows rate isomorphy or
      not was determined over a range of temperatures where the relationship between
      the rate of development and temperature is linear. Proportion of total
      developmental time spent in a particular stage was plotted against temperature
      and the existence of rate isomorphy inferred from a zero change in proportion.
      Rate isomorphy was detected in 243 (57%) of 426 populations. In the rest of the
      cases, rate isomorphy was violated by deviations in the proportion of time spent
      in a stage by an average of 0.2% (range 4.5E-06% to 2.8%) at the mean of the
      range of temperatures of all the data sets (11 degrees C). The violations
      occurred most frequently at the extremes of the linear phase, which is attributed
      to methodical biases, mortality at low temperatures, or too coarse an estimate of
      developmental time at high temperatures. Similarly, a meta-analysis also revealed
      an overall prevalence of rate isomorphy. Consequently, in insect and mite
      species, all the developmental stages appear to have the same population-specific
      lower developmental threshold. The existence of rate isomorphy could be of great
      practical importance, for example, in the timing of life-history events and in
      determining preadult thermal requirements. There are also indications that it may
      act as a phylogenetic constraint.

PMID- 18707526
TI  - Testing for environmentally induced bias in phenotypic estimates of natural
      selection: theory and practice.
AB  - Measuring natural selection has been a fundamental goal of evolutionary biology
      for more than a century, and techniques developed in the last 20 yr have provided
      relatively simple means for biologists to do so. Many of these techniques,
      however, share a common limitation: when applied to phenotypic data,
      environmentally induced covariances between traits and fitness can lead to biased
      estimates of selection and misleading predictions about evolutionary change.
      Utilizing estimates of breeding values instead of phenotypic data with these
      methods can eliminate environmentally induced bias, although this approach is
      more difficult to implement. Despite this potential limitation to phenotypic
      methods and the availability of a potential solution, little empirical evidence
      exists on the extent of environmentally induced bias in phenotypic estimates of
      selection. In this article, we present a method for detecting bias in phenotypic
      estimates of selection and demonstrate its use with three independent data sets.
      Nearly 25% of the phenotypic selection gradients estimated from our data are
      biased by environmental covariances. We find that bias caused by environmental
      covariances appears mainly to affect quantitative estimates of the strength of
      selection based on phenotypic data and that the magnitude of these biases is
      large. As our estimates of selection are based on data from spatially replicated
      field experiments, we suggest that our findings on the prevalence of bias caused
      by environmental covariances are likely to be conservative.

PMID- 18707527
TI  - Self-organization of vegetation in arid ecosystems.

PMID- 18707528
TI  - Behavior at habitat boundaries can produce leptokurtic movement distributions.

PMID- 18707529
TI  - Differential mobilization of blubber fatty acids in lactating Weddell seals:
      evidence for selective use.
AB  - A major source of energy during lactation in mammals is provided through the
      mobilization of blubber fatty acids (FAs). We investigated the extent to which
      FAs were mobilized to support both maternal metabolic requirements and milk
      production in the Weddell seal and how this was reflected in the FA composition
      of the pup's blubber at the end of lactation (EL). FA composition of postpartum
      female blubber was similar in the 2 yr of study (2002 and 2003) but differed
      markedly by EL. Pup blubber FAs (at EL) were also different between years and did
      not match that of the mother's milk or blubber. Milk FA composition changed
      during lactation, which may have been a reflection of an increase in pup energy
      demands at different stages of development. In addition, there was evidence of
      feeding by some females during lactation, with higher levels of some FAs in the
      milk than in the blubber. Our results indicate that differential mobilization of
      FAs occurred in lactating Weddell seals and that this was related to total body
      lipid stores at postpartum. Furthermore, growing pups did not store FAs
      unmodified, providing evidence that selective use does occur and also that using
      FA composition to elucidate dietary sources may be problematic in growing
      individuals.

PMID- 18707530
TI  - Caste determination in a polymorphic social insect: nutritional, social, and
      genetic factors.
AB  - We examined how dietary, social, and genetic factors affect individual size and
      caste in the Florida harvester ant Pogonomyrmex badius, which has three discrete
      female castes. The diet that a larva consumed, as indicated by delta(13)C,
      delta(15)N, and C:N, varied with caste. Both N content and estimated trophic
      position of dietary input was higher for major than for minor workers and was
      highest for gynes (reproductive females). The size and resources of a colony
      affected the size of only minor workers, not that of gynes and major workers.
      Approximately 19% of patrilines showed a bias in which female caste they
      produced. There were significant genetic effects on female size, and the average
      sizes of a major worker and a gyne produced by a patriline were correlated, but
      neither was correlated with minor worker size. Thus, genetic factors influence
      both caste and size within caste. We conclude that environmental, social, and
      genetic variation interact to create morphological and physiological variation
      among females in P. badius. However, the relative importance of each type of
      factor affecting caste determination is caste specific.

PMID- 18707531
TI  - Farm-level impact of therapeutic antimicrobial use on antimicrobial-resistant
      populations of Escherichia coli isolates from pigs.
AB  - We investigated the farm-level impact of the use of several different
      antimicrobial agents on the population of antimicrobial-resistant commensal
      bacteria of animal origin to appropriately assess the release risk of resistance.
      This study was carried out based on the results of a survey on the history of
      antimicrobial drug use in 297 pig farms and antimicrobial susceptibility testing
      for the 545 Escherichia coli isolates (one or two isolates/pig/farm). A
      comparative analysis with the nonexposed herd revealed that ampicillin (ABPC)
      resistance in E. coli increased in the herds that were exposed to penicillin
      (relative risk [RR], 1.75) and penicillin-streptomycin (RR, 2.28);
      dihydrostreptomycin (DSM) resistance, in the penicillin-streptomycin-exposed herd
      (RR, 1.75); and trimethoprim (TMP) resistance in the methoprim-sulfonamide
      exposed herd (RR, 2.10). On the other hand, ABPC and DSM resistances increased in
      the tetracycline-exposed herd (RR, 1.66 and 1.58, respectively); TMP resistance,
      in the penicillin-exposed herd (RR, 1.77); and oxytetracycline and kanamycin
      resistances, in the penicillin-streptomycin-exposed herd (RR, 1.28 and 2.22,
      respectively). These results demonstrated that the development of cross
      resistance and coresistance, imposed by the therapeutic use of the antimicrobials
      studied, contributed the farm-level prevalence of antimicrobial-resistant E. coli
      and that the influence of coselection was characteristic to individual
      antimicrobial agents used.

PMID- 18707532
TI  - Gender differences among hardcore smokers: an analysis of the tobacco use
      supplement of the current population survey.
AB  - BACKGROUND: Despite significant declines in smoking rates in the United States, a
      substantial percentage of adults continue to smoke. Improved understanding of
      current smokers and their contact with sources of cessation support future
      tobacco control efforts. Recent evidence suggests that hardcore smokers,
      established smokers without a history of quit attempts, have less contact with
      cessation support. Although gender is among the major factors that influence
      smoking cessation, no research is available on gender differences among hardcore
      smokers. METHODS: Demographic, environmental, and smoking-related characteristics
      of female hardcore smokers and male hardcore smokers and other female smokers
      were examined. Data from 17,777 smokers from the 2003 Current Population Survey
      Tobacco Use Supplement were analyzed. RESULTS: Compared with female hardcore
      smokers, male hardcore smokers were more likely to have contact with smoking
      restrictions at work (OR = 1.69) and at home (OR = 1.45). Compared with female
      hardcore smokers, female other smokers were more likely to have seen a healthcare
      provider during the past year who advised them to quit smoking (OR = 1.39) and
      more likely to have smoking restrictions at work (OR = 1.25) and at home (OR =
      2.32)). Measures of nicotine dependence suggested that female hardcore smokers
      were less dependent than male hardcore smokers but more dependent than other
      female smokers. CONCLUSIONS: The sociodemographic and healthcare access
      variations in tobacco use identified in our analyses have significant public
      health implications and underscore the vital need for clinical and scientific
      advances in tobacco use prevention and control efforts.

PMID- 18707533
TI  - QNet: a tool for querying protein interaction networks.
AB  - Molecular interaction databases can be used to study the evolution of molecular
      pathways across species. Querying such pathways is a challenging computational
      problem, and recent efforts have been limited to simple queries (paths), or
      simple networks (forests). In this paper, we significantly extend the class of
      pathways that can be efficiently queried to the case of trees, and graphs of
      bounded treewidth. Our algorithm allows the identification of non-exact
      (homeomorphic) matches, exploiting the color coding technique of Alon et al.
      (1995). We implement a tool for tree queries, called QNet, and test its retrieval
      properties in simulations and on real network data. We show that QNet searches
      queries with up to nine proteins in seconds on current networks, and outperforms
      sequence-based searches. We also use QNet to perform the first large-scale cross
      species comparison of protein complexes, by querying known yeast complexes
      against a fly protein interaction network. This comparison points to strong
      conservation between the two species, and underscores the importance of our tool
      in mining protein interaction networks.

PMID- 18707534
TI  - Estimating genome-wide copy number using allele-specific mixture models.
AB  - Genomic changes such as copy number alterations are one of the major underlying
      causes of human phenotypic variation among normal and disease subjects. Array
      comparative genomic hybridization (CGH) technology was developed to detect copy
      number changes in a high-throughput fashion. However, this technology provides
      only a >30-kb resolution, which limits the ability to detect copy number
      alterations spanning small regions. Higher resolution technologies such as single
      nucleotide polymorphism (SNP) microarrays allow detection of copy number
      alterations at least as small as several thousand base pairs. Unfortunately,
      strong probe effects and variation introduced by sample preparation procedures
      have made single-point copy number estimates too imprecise to be useful. Various
      groups have proposed statistical procedures that pool data from neighboring
      locations to successfully improve precision. However, these procedure need to
      average across relatively large regions to work effectively, thus greatly
      reducing resolution. Recently, regression-type models that account for probe
      effects have been proposed and appear to improve accuracy as well as precision.
      In this paper, we propose a mixture model solution, specifically designed for
      single-point estimation, that provides various advantages over the existing
      methodology. We use a 314-sample database, to motivate and fit models for the
      conditional distribution of the observed intensities given allele-specific copy
      number. We can then compute posterior probabilities that provide a useful
      prediction rule as well as a confidence measure for each call. Software to
      implement this procedure will be available in the Bioconductor oligo package
      (www.bioconductor.org).

PMID- 18707535
TI  - RB-finder: an improved distance-based sliding window method to detect
      recombination breakpoints.
AB  - Recombination detection is important before inferring phylogenetic relationships.
      This will eventually lead to a better understanding of pathogen evolution, more
      accurate genotyping, and advancements in vaccine development. In this paper, we
      introduce RB-Finder, a fast and accurate distance-based window method to detect
      recombination in a multiple sequence alignment. Our method introduces a more
      informative distance measure and a novel weighting strategy to reduce the window
      size sensitivity problem and hence improve the accuracy of breakpoint detection.
      Furthermore, our method is faster than existing phylogeny-based methods since we
      do not need to construct and compare complex phylogenetic trees. When compared
      with the current best method Pruned-PDM, our method is a few hundred times more
      efficient. Experimental evaluation of RB-Finder using synthetic and biological
      datasets showed that our method is more accurate than existing phylogeny-based
      methods. We also show how our method has potential use in other related
      applications such as genotyping.

PMID- 18707537
TI  - Multivariate segmentation in the analysis of transcription tiling array data.
AB  - Tiling DNA microarrays extend current microarray technology by probing the non
      repeat portion of a genome at regular intervals in an unbiased fashion. A
      fundamental problem in the analysis of these data is the detection of genomic
      regions that are differentially transcribed across multiple conditions. We
      propose a linear time algorithm based on segmentation techniques and linear
      modeling that can work at a user-selected false discovery rate (FDR). It also
      attains a fourfold sensitivity gain over the only competing algorithm when
      applied to a whole genome transcription data set spanning the embryonic
      development of Drosophila melanogaster.

PMID- 18707536
TI  - Support vector training of protein alignment models.
AB  - Sequence to structure alignment is an important step in homology modeling of
      protein structures. Incorporation of features such as secondary structure,
      solvent accessibility, or evolutionary information improve sequence to structure
      alignment accuracy, but conventional generative estimation techniques for
      alignment models impose independence assumptions that make these features
      difficult to include in a principled way. In this paper, we overcome this problem
      using a Support Vector Machine (SVM) method that provides a well-founded way of
      estimating complex alignment models with hundred of thousands of parameters.
      Furthermore, we show that the method can be trained using a variety of loss
      functions. In a rigorous empirical evaluation, the SVM algorithm outperforms the
      generative alignment method SSALN, a highly accurate generative alignment model
      that incorporates structural information. The alignment model learned by the SVM
      aligns 50% of the residues correctly and aligns over 70% of the residues within a
      shift of four positions.

PMID- 18707538
TI  - Minimizing and learning energy functions for side-chain prediction.
AB  - Side-chain prediction is an important subproblem of the general protein folding
      problem. Despite much progress in side-chain prediction, performance is far from
      satisfactory. As an example, the ROSETTA program that uses simulated annealing to
      select the minimum energy conformations, correctly predicts the first two side
      chain angles for approximately 72% of the buried residues in a standard data set.
      Is further improvement more likely to come from better search methods, or from
      better energy functions? Given that exact minimization of the energy is NP hard,
      it is difficult to get a systematic answer to this question. In this paper, we
      present a novel search method and a novel method for learning energy functions
      from training data that are both based on Tree Reweighted Belief Propagation
      (TRBP). We find that TRBP can obtain the global optimum of the ROSETTA energy
      function in a few minutes of computation for approximately 85% of the proteins in
      a standard benchmark set. TRBP can also effectively bound the partition function
      which enables using the Conditional Random Fields (CRF) framework for learning.
      Interestingly, finding the global minimum does not significantly improve side
      chain prediction for an energy function based on ROSETTA's default energy terms
      (less than 0:1%), while learning new weights gives a significant boost from 72%
      to 78%. Using a recently modified ROSETTA energy function with a softer Lennard
      Jones repulsive term, the global optimum does improve prediction accuracy from
      77% to 78%. Here again, learning new weights improves side-chain modeling even
      further to 80%. Finally, the highest accuracy (82.6%) is obtained using an
      extended rotamer library and CRF learned weights. Our results suggest that
      combining machine learning with approximate inference can improve the state-of
      the-art in side-chain prediction.

PMID- 18707539
TI  - Potent knockdown of the X RNA of hepatitis B by a novel chimeric siRNA-ribozyme
      construct and modulation of intracellular target RNA by selectively disabled
      mutants.
AB  - A multitarget approach is needed for effective gene silencing that combines more
      than one antiviral strategy. With this in mind, we designed a wild-type (wt) and
      selectively disabled chimeric mutant (mt) constructs that consisted of small
      hairpin siRNA joined by a short intracellular cleavable linker to a known
      hammerhead ribozyme, both targeted against the full-length X RNA of hepatitis B.
      These chimeric RNAs possessed the ability to cleave the target RNA under in vitro
      conditions and were efficiently processed at the cleavable site. When this wt
      chimeric RNA construct was introduced into a liver-specific mammalian cell line,
      HepG2, along with the HBx substrate encoding DNA, very significant (approximately
      70%) intracellular downregulation in the levels of target RNA was observed. When
      the siRNA portion of this chimeric construct was mutated, keeping the ribozyme
      (Rz) region unchanged, it caused only approximately 25% intracellular reduction.
      On the contrary, when only the Rz was made catalytically inactive, about 55%
      reduction in the target RNA was observed. Construct possessing mt Rz and mt siRNA
      caused only 10% reduction. This wt chimeric construct also resulted in almost
      complete knockdown of intracellular HBx protein production, and the mt versions
      were less effective. The intracellular reduction of target RNA with either wt or
      mt constructs also interfered with the known functions of HBx protein with
      varying efficiencies. Thus, in this proof of concept study we show that the
      levels of the target RNA were reduced potently by the wt chimeric siRNA-Rz
      construct, which could be modulated with mt versions of the same.

PMID- 18707540
TI  - An efficient biodelivery system for antisense polyamide nucleic acid (PNA).
AB  - With the aim of developing a general and straightforward procedure for the
      intracellular delivery of naked peptide nucleic acids (PNAs), we designed an
      intracellularly biodegradable triphenylphosphonium (TPP) cation based transporter
      system. In this system, TPP is linked, via a biolabile disulfide bridge, to an
      activated mercaptoethoxycarbonyl moiety, allowing its direct coupling to the N
      terminal extremity of a free PNA through a carbamate bond. We found that such TPP
      PNA-carbamate conjugates were highly stable in a cell culture medium containing
      fetal calf serum. In a glutathione-containing medium mimicking the cytosol, the
      conjugates were rapidly degraded into an unstable intermediate, which
      spontaneously decomposed, releasing the free PNA. Using a fluorescence-labeled
      PNA-TPP conjugate, we demonstrated that conjugates were taken up by cells.
      Efficient cellular uptake and release of the PNA into the cytosol was further
      confirmed by the anti-HIV activity measured for the TPP-conjugate of a 16-mer PNA
      targeting the TAR region of the HIV-1 genome. This conjugate exhibited an IC(50)
      value of 1 microM, while the free 16-mer PNA did not inhibit replication of HIV
      in the same cellular test.

PMID- 18707541
TI  - Relationship between antigenicity and pathogenicity for Burkholderia pseudomallei
      and Burkholderia mallei revealed by a large panel of mouse MAbs.
AB  - Burkholderia pseudomallei and Burkholderia mallei are two closely related gram
      negative bacterial species classified by the CDC as category B biowarfare agents.
      To develop monoclonal antibodies (MAbs) that can recognize as many different
      strains and/or clinical isolates of these two pathogens as possible, we immunized
      mice with heat-killed bacterial whole cells and membrane preparations from
      multiple strains and/or clinical isolates of B. pseudomallei and B. mallei. More
      than 100 different hybridoma clones that produced MAbs strongly reacting to B.
      pseudomallei and/or B. mallei have been developed. These MAbs were categorized
      into eight different groups according to their reaction specificity against
      different species of Burkholderia bacteria as well as the different nature of
      target antigens (LPS, capsule polysaccharides, proteins, and glycoproteins) on
      the bacteria they recognized. Characterization of this large panel of MAbs has
      demonstrated an interesting pattern of various antigenic epitopes shared by the
      different species of Burkholderia bacteria. More importantly, this study has
      revealed a pathogenicity-linked antigen epitope(s) on capsule-like
      polysaccharides found only in the pathogenic species of Burkholderia bacteria and
      a Burkholderia-specific antigen epitope(s) that did not exist in other gram
      negative bacterial species. Our MAbs should prove to be highly valuable in the
      development of detection, diagnosis, and therapeutic applications against B.
      mallei and B. pseudomallei infections.

PMID- 18707542
TI  - Plant-produced hepatitis B core protein chimera carrying anthrax protective
      antigen domain-4.
AB  - The hepatitis B core antigen (HBcAg) can generate a strong immune response and is
      recognized as an effective carrier for foreign epitopes. The domain-4 epitope of
      the anthrax protective antigen (PA-D4) plays an essential role in generating
      protective immunity against virulent Bacillus anthracis. Here we report the
      successful production of a recombinant protein comprised of the antigenic PA-D4
      integrated into the c/e1 loop of HBcAg in transgenic low-alkaloid Nicotiana
      tabacum. Sera of mice injected with the plant-derived purified HB/PA-D4 protein
      exhibited significant anti-PA- and anti-HBcAg-specific IgG titers; however,
      formation of virus-like particles (VLP) was not observed. These data support the
      feasibility of producing complex protein chimeras in plants.

PMID- 18707544
TI  - Characterization of anti-podoplanin monoclonal antibodies: critical epitopes for
      neutralizing the interaction between podoplanin and CLEC-2.
AB  - Podoplanin (Aggrus) is a mucin-type sialoglycoprotein that is known as a useful
      marker for lymphatic endothelium and tumor-initiating cells (TICs). Interaction
      between podoplanin and C-type lectin-like receptor-2 (CLEC-2) is reported to be
      critical for podoplanin-induced platelet aggregation and cancer metastasis.
      Recently, several anti-human podoplanin antibodies have been created; however,
      these anti-podoplanin antibodies have not been well characterized. Five anti
      podoplanin antibodies (NZ-1, D2-40, AB3, 18H5, and a rabbit polyclonal antibody)
      were investigated using ELISA, Western blot, and flow cytometry with synthesized
      podoplanin peptides and deletion mutants of recombinant podoplanin. The epitope
      of NZ-1 is platelet aggregation-stimulating (PLAG) domain-2/3; the epitope of D2
      40, AB3, and 18H5 is PLAG1/2. The epitopes of D2-40 and AB3 are quite similar,
      although 18H5 is different from D2-40 and AB3. Using flow cytometric analysis, NZ
      1 partially inhibited the interaction between podoplanin and CLEC-2, although
      other antibodies did not. In conclusion, the two most frequently used anti
      podoplanin antibodies, D2-40 and AB3, have similar properties, although several
      studies have reported differences. NZ-1 neutralizes the interaction between
      podoplanin and CLEC-2, which may lead to the development of therapeutic
      antibodies against podoplanin-dependent cancer metastasis.

PMID- 18707543
TI  - Generation and characterization of monoclonal antibodies against the proregion of
      human desmoglein-2.
AB  - Abstract Cadherins are synthesized with a signal sequence and a proregion that
      must be removed for optimal adhesive activity. Mutations that prevent processing
      of cadherins have been implicated in a number of human diseases; thus
      understanding their processing is critical. In this study, we produced and
      characterized a number of monoclonal antibodies against the proregion of the
      desmosomal cadherin, human desmoglein-2, that will facilitate investigations into
      the processing of this protein.

PMID- 18707545
TI  - High-expression of monoclonal nanobodies used in the preparation of HRP
      conjugated second antibody.
AB  - Camelids produce functional antibodies devoid of light chains and constant heavy
      chain domain (CH1). The antigen binding fragments of such heavy-chain antibodies
      are therefore comprised in one single domain, the so-called VH of the camelid
      heavy-chain antibody (VHH) or nanobody. The very close similarity of these
      molecules to human VHs illustrated the potential application of these novel
      products as an immunodiagnostic and immunotherapeutic reagent, so the anti
      nanobody HRP conjugate is one of the key components in production,
      characterization, and application of these molecules in detection and therapy.
      These antigen-specific fragments are well expressed in Escherichia coli. Here we
      report high expression and purification of some nanobodies against tumor markers.
      The nanobody genes were subcloned into a pET22b(+) vector to overexpress the
      protein coupled with fusion tag in E. coli. The expressed nanobodies were
      purified by immobilized metal affinity chromatography and injected into rabbits
      as an immunogen. Described here are the preparation, purification, and
      characterization of anti-nanobody HRP conjugate for use in the various nanobody
      immunoassay systems. Several biochemical modifications were applied to increase
      the sensitivity and specificity of this conjugate for an efficient and cost
      effective product. We concluded that the present reagent can detect nanobodies in
      various detection procedures with great sensitivity and accuracy.

PMID- 18707546
TI  - Generation and characterization of a monoclonal antibody against NPI-1 subfamily
      of importin alpha.
AB  - Most karyophilic proteins are transported into the nucleus through the importin
      mediated pathway. Importin alpha acts as a receptor for classical nuclear
      localization signal (NLS)-containing proteins. At present, the existence of
      several isoforms of importin alpha in mammals is known. In this study we report
      on the generation of a rat monoclonal antibody (MAb) 2D9 to importin alpha NPI-1
      subfamily members (importin alpha5/NPI-1 and importin alpha7/S2) using the rat
      lymph node method and the characterization of this antibody. In several different
      cultured cell extracts, MAb 2D9 reacted to endogenous NPI-1 subfamily in Western
      blotting experiments. Epitope mapping using recombinant deletion mutants
      indicated that MAb 2D9 recognized arm motif in importin alpha5/NPI-1. Using
      immunofluorescence, MAb 2D9 detected NPI-1 subfamily in the cytoplasm of HeLa
      cells. Moreover, endogenous NPI-1 subfamily was dominantly localized in the
      nuclei of H(2)O(2)-treated HeLa cells, suggesting that NPI-1 subfamily
      accumulates in the nucleus in response to oxidative stress, like importin
      alpha1/Rch1.

PMID- 18707547
TI  - Towards the definition of a chimpanzee and human conserved CD6 domain 1 epitope
      recognized by T1 monoclonal antibody.
AB  - Scavenger receptor cysteine-rich (SRCR) domains are evolutionally conserved
      modules that display complex structures stabilized by key amino acids, while some
      other residues have evolved with a relative independence, thus allowing the
      functional diversity of these receptors. CD6, a highly glycosylated membrane
      protein predominantly expressed on lymphocytes, contains three SRCR domains. The
      lack of CD6 domain crystal structure has limited the characterization of the
      binding sites for the interacting molecules. The interaction between CD6 and its
      ligand, activated leukocyte-cell adhesion molecule (ALCAM)/CD166, through the
      membrane-proximal SRCR3 domain, has low affinity and involves conserved sites in
      both molecules mediating a cross-species binding. The CD6-ALCAM interaction has
      been involved in cell adhesion, maturation, regulation of activation, and
      survival processes, suggesting the potential relevance of this target for
      therapeutic interventions. Several anti-CD6 monoclonal antibodies (MAb) have been
      described but their affinity and epitope definition remain unclear. We found the
      murine and humanized T1 MAb versions have similar CD6 recognition profiles and
      affinity constants of about 6 x 10(8). These antibodies do not block the CD6
      ALCAM interaction and recognize a conformational epitope independent of the CD6 N
      glycosylation. This epitope was additionally found in the chimpanzee and contains
      an RXE/Q consensus motif located in the membrane-distal SRCR1. These results,
      together with the therapeutic evidence previously obtained with these MAbs,
      suggest a differential contribution of CD6 domains to lymphocyte biology.
      Potential mechanisms for T1 MAb therapeutic effect different from CD6-CD166
      interaction blocking would be dissected.

PMID- 18707548
TI  - Utilization of monoclonal antibodies for detection of Plasmodium falciparum
      antigen in cerebrospinal fluid of cerebral malaria patients.
AB  - A uniform protein profile of bands at 34, 43, and 52 kDa was obtained with all
      the cerebrospinal fluid (CSF) samples of malaria (10 in number) and non-malaria
      patients (31 in number) by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE). An immunoreactive band was observed at 43 kDa in CSF
      samples of cerebral malaria patients but not in non-malaria cases when tested
      with rabbit anti-Plasmodium falciparum antibodies by Western blot analysis.
      Eleven reactive monoclonal antibodies against P. falciparum were stabilized and
      expanded. Nine monoclonal antibodies were reactive to CSF samples of cerebral
      malaria and non-malaria and P. falciparum antigen by dot-ELISA and a common
      immunoreactive band at 43 kDa by Western blot. One clone Cl-2 was reactive at 43
      kDa with CSF of the cerebral malaria patients and also in P. falciparum antigen
      but at 66 kDa with non-malarial CSF samples in Western blot. The other two clones
      (Cl-6 and 14) reacted with 3/31 (90% specific) and 8/31 (74%) CSF samples of non
      malaria patients, respectively. The monoclonal antibody based ELISA reported in
      the present study using clone-6 can therefore offer another possibility for
      developing rapid, easy-to-perform, low-cost tests for diagnosis of cerebral
      malaria in CSF samples. Western blot using clone-2 might be useful for the
      detection of cerebral malaria antigen in CSF.

PMID- 18707549
TI  - A novel approach to development of monoclonal antibodies using native antigen for
      immunization and recombinant antigen for screening.
AB  - The production of monoclonal antibodies (MAb) specific to microbes is rapidly
      growing. Finding an appropriate antigen to screen hybridoma clones has become
      increasingly important. However, the conventional method, in which the purified
      antigen from the microbe is routinely used for screening, cannot avoid selection
      of false positive hybridoma clones, since even highly purified antigen is found
      to be contaminated with some other proteins from the microbe. In this study, MAbs
      against anthrax protective antigen (PA), the central component of the three-part
      toxin secreted by Bacillus anthracis were developed using a pair of the roughly
      purified native PA as an immunogen and the recombinant PA as a screening antigen
      without any possibility of false selection, since the recombinant PA was produced
      by a gene engineering approach and impossible to be contaminated with any other
      proteins from B. anthracis. In total, nine stable hybridoma clones secreting anti
      PA MAbs were developed. All of them had the same type of heavy and light chains,
      IgG1/kappa. The binding profiles for these anti-PA MAbs were investigated by
      ELISA. This novel approach to the development of MAbs should be applicable to the
      production of MAbs to other microbes, especially to those from which antigens can
      hardly be purified to a high degree.

PMID- 18707550
TI  - Generation and characterization of novel monoclonal antibodies against human
      aurora-A.
AB  - The mitotic kinase Aurora-A is essential for mitotic progression, including
      centrosome maturation, mitotic spindle formation, and faithful segregation of
      chromosomes to daughter cells. Several lines of evidences also suggest that the
      mammalian aurora kinase family proteins play a role in tumorigenesis. We have
      previously shown that human Aurora-A was ubiquitinated and negatively regulated
      by an early mitotic checkpoint protein, Chfr (checkpoint protein with FHA and
      RING domain). Here, we established several mouse anti-Aurora-A monoclonal
      antibodies (MAb). GST-tagged human Aurora-A was expressed in BL21 and used as an
      antigen to immunize mice. Three different hybridomas were obtained and antibodies
      produced by these hybridomas were analyzed. The results reveal that these
      antibodies specifically recognize endogenous Aurora-A in both immunoblotting and
      immunofluroscence experiments. They are useful tools for further analysis of
      human Aurora-A.

PMID- 18707551
TI  - Transition mutations in 23S rRNA account for acquired resistance to macrolides in
      Ureaplasma urealyticum.
AB  - OBJECTIVE: To study the mechanisms of acquired resistance of Ureaplasma
      urealyticum (Uu) to Macrolide antibiotics. METHODS: Eighteen strains of Uu
      clinical isolates with different phenotypes of resistance to Macrolide
      antibiotics were screened for mutations in 23S rRNA in comparison with the
      reference strain ATCC 27618 and AF272627-1 in GenBank, which is susceptible to
      Macrolide antibiotics. RESULTS: Compared to the sequence of reference strains
      ATCC 27618 and AF272627-1, three transitions were found in 23S rRNA of Uu
      clinical isolates with acquired resistance to Macrolide antibiotics. The C2243N
      (T or C) transition was found in the 23S rRNA sequence of five strains with the
      phenotype of acquired resistance to Roxithromycin (ROM) and Azithromycin (AZM).
      The two changes of A2149C and A2181T were found in the 23S rRNA sequence of nine
      strains with the phenotype of resistance to ROM and midrange resistance to AZM,
      and they were also found in that of four strains with the phenotype of
      sensitivity to macrolides (Josamycin, Clarithromycin, ROM, and AZM). No mutation
      was found in the ATCC 27618. CONCLUSION: The mechanisms of Uu resistance to ROM
      and AZM may be associated with the C2243N (T or C) mutation in 23S rRNA. Further
      studies are necessary to confirm this hypothesis.

PMID- 18707552
TI  - Rapid emergence of blaCTX-M among Enterobacteriaceae in U.S. Medical Centers:
      molecular evaluation from the MYSTIC Program (2007).
AB  - A total of 220 gram-negative isolates showing distinct beta-lactam resistance
      profiles recovered in U.S. medical centers during the MYSTIC Program 2007 were
      evaluated to determine the presence of selected beta-lactamase genes. CTX-M
      encoding genes, considered rare in the United States, were detected in 38.8%
      (28/70; three species) of the extended spectrum beta-lactamase-positive isolates
      and were observed in 80.0% of the participating hospitals. CTX-M-14 and -15 were
      found in multiple institutions (eight and nine medical centers, respectively),
      and CTX-M-3 was detected in only one isolate. The OXA-2 and -10 were identified
      in nine Enterobacteriaceae strains, and plasmid-mediated AmpC enzymes CMY-2 and
      FOX-5 were identified in six and four isolates, respectively, displaying negative
      clavulanate inhibition. Genes encoding OXA-23 and -24 were detected in 30.0%
      (15/50) of carbapenem-resistant Acinetobacter spp. strains. Retrospective
      sampling showed that these OXA enzymes were present since 2004 in the MYSTIC
      Program isolates. The KPC serine carbapenemases were observed in the majority of
      the carbapenem-resistant Enterobacteriaceae (usually Klebsiella pneumoniae),
      confirming an epidemic problem in the New York City area. The association of beta
      lactamase production and transferable quinolone resistance genes (qnr; 6.7%) in
      Enterobacteriaceae strains was higher than previously reported. This study
      illustrates the emergence and rapid dissemination of some beta-lactamases, such
      as CTX-M, broad-spectrum oxacillinases, and serine carbapenemases, that
      compromised the treatment of gram-negative infections in numerous U.S. hospitals
      participating in the MYSTIC Program in 2007.

PMID- 18707553
TI  - Effects of the 7-valent pneumococcal conjugate vaccine on U.S. levofloxacin
      resistant Streptococcus pneumoniae.
AB  - BACKGROUND: Seven-valent pneumococcal conjugate vaccine (PCV7) provides
      protection against invasive pneumococcal disease that extends to unvaccinated
      populations, such as elderly or immunocompromised adults. PCV7 also reduces
      incidence of pneumococcal penicillin resistance. In this study, the potential
      impact of PCV7 on pneumococcal fluoroquinolone resistance was examined. METHODS:
      U.S. levofloxacin-resistant isolates (264) from TRUST surveillance studies (1999
      2004) were serotyped and quinolone resistance-determining region of parC/E and
      gyrA/B sequenced. Changes in prevalence of vaccine/nonvaccine serotypes during
      2000-2004 and 1999-2004 were analyzed by regression analyses and chi-square trend
      test. RESULTS: The introduction of PCV7 (2000-2004) did not affect
      fluoroquinolone resistance prevalence, but mutants with vaccine serotypes
      declined linearly at -6.6 +/- 0.8% per year (p = 0.003), with concomitant
      replacement by nonvaccine serotypes; vaccine-related serotypes (6A, 9N, 19A, and
      23N) increased (p = 0.04). Differential selection between vaccine and nonvaccine
      serotypes occurred for mutants containing amino acid substitutions at either ParC
      Ser79 (p = 0.01) or both ParC Ser79 and GyrA Ser81 (p = 0.04). Among mutants with
      ParC Ser79 substitutions, vaccine serotypes declined linearly (p = 0.02), whereas
      nonvaccine serotypes increased (p = 0.04). Additionally, a vaccine-independent
      effect became apparent during 1999-2004, as the incidence of ParC Ser79 and Asp83
      mutations declined in fluoroquinolone-resistant strains, suggesting that these
      substitutions conferred decreased fitness. CONCLUSIONS: PCV7 has led to extensive
      replacement of vaccine serotypes by nonvaccine serotypes among levofloxacin
      resistant pneumococci.

PMID- 18707554
TI  - High rates of plasmid-mediated quinolone resistance QnrB variants among
      ciprofloxacin-resistant Escherichia coli and Klebsiella pneumoniae from urinary
      tract infections in Korea.
AB  - The aims of this study were to investigate the prevalence of qnrA, qnrB, and qnrS
      determinants and their molecular characteristics in ciprofloxacin-resistant
      isolates of Escherichia coli and Klebsiella pneumoniae from urinary tract
      infections (UTI) in Korea. A total of 202 nonduplicated clinical isolates of
      ciprofloxacin-resistant E. coli (n = 143) and K. pneumoniae (n = 59) were
      collected between July 2005 and August 2006. The qnr determinant screening was
      carried out by PCR amplification of qnrA, qnrB, and qnrS, and all positive
      results were confirmed by direct sequencing of the PCR products. For qnr-positive
      strains and their conjugants, antimicrobial susceptibility tests and pulsed-field
      gel electrophoresis (PFGE) were performed. The qnrB gene was detected in 41 of
      the 202 isolates. Among 33 of 59 (55.9%) K. pneumoniae isolates showing qnrB, 29
      isolates contained the qnrB4 gene, 3 isolates had the qnrB2 gene, and 1 isolate
      had the qnrB6 gene. All 8 (5.6%) of the qnrB-positive isolates among the 143 E.
      coli strains possessed the qnrB4 gene. The minimum inhibitory concentrations
      (MICs) of ciprofloxacin for the transconjugants were 0.03-2 mug/ml, representing
      an increase of 4- to 256-fold relative to the recipient, E. coli J53Az(r).
      Resistances to various other antimicrobial agents also were transferred with the
      plasmid. The PFGE analysis revealed indistinguishable or closely related patterns
      in several strains and highly diverse patterns in general. QnrB variants,
      especially the qnrB4 subtype, are highly prevalent in ciprofloxacin-resistant E.
      coli and K. pneumoniae from UTI in Korea. The emergence of plasmid-mediated
      quinolone resistance may contribute by several means to the rapid increase in
      bacterial resistance to these drugs.

PMID- 18707555
TI  - Investigation of Panton-Valentine leukocidin genes and SCCmec types in clinical
      Staphylococcus aureus isolates from Turkey.
AB  - Panton-Valentine leukocidin (PVL) is an important virulence determinant of
      Staphylococcus aureus. The aim of this study was to investigate the prevalence of
      PVL genes in clinical S. aureus isolates and to determine the staphylococcal
      chromosomal cassette mec (SCCmec) types of methicillin-resistant S. aureus (MRSA)
      strains obtained from inpatients and outpatients of two hospitals in Turkey. Of
      the 304 S. aureus strains (230 hospital acquired [HA] and 74 community-onset
      [CO]), 261 were MRSA and 43 were methicillin-sensitive S. aureus (MSSA). PVL
      positivity was determined in 12 (1 HA and 11 community acquired) strains. Eight
      were MRSA, and four were MSSA. Seven of the PVL-positive strains were isolated
      from wound specimens, four from urine, and one from synovial fluid. SCCmec type
      III (93.78%) was more prevalent among HA-MRSA strains, and SCCmec type IIIB
      (41.18%) was more prevalent among CO-MRSA strains. Pulsed-field gel
      electrophoresis patterns of the PVL-positive isolates were different. Our results
      indicate that PVL-positive strains are able to cause infection in nearly every
      system without the need for additional risk factors. Our PVL-positive CO-MRSA
      strains carry SCCmec types other than types IV and V. Due to the presence of PVL
      positive strains in the hospitals, it is important to establish appropriate
      infection control measures to prevent their spread in the community and in
      hospitals.

PMID- 18707556
TI  - Computational quantification of peptides from LC-MS data.
AB  - Liquid chromatography coupled to mass spectrometry (LC-MS) has become a major
      tool for the study of biological processes. High-throughput LC-MS experiments are
      frequently conducted in modern laboratories, generating an enormous amount of
      data per day. A manual inspection is therefore no longer a feasible task.
      Consequently, there is a need for computational tools that can rapidly provide
      information about mass, elution time, and abundance of the compounds in a LC-MS
      sample. We present an algorithm for the detection and quantification of peptides
      in LC-MS data. Our approach is flexible and independent of the MS technology in
      use. It is based on a combination of the sweep line paradigm with a novel wavelet
      function tailored to detect isotopic patterns of peptides. We propose a simple
      voting schema to use the redundant information in consecutive scans for an
      accurate determination of monoisotopic masses and charge states. By explicitly
      modeling the instrument inaccuracy, we are also able to cope with data sets of
      different quality and resolution. We evaluate our technique on data from
      different instruments and show that we can rapidly estimate mass, centroid of
      retention time, and abundance of peptides in a sound algorithmic framework.
      Finally, we compare the performance of our method to several other techniques on
      three data sets of varying complexity.

PMID- 18707558
TI  - Alcohol sales data are essential for good public policies towards alcohol.

PMID- 18707557
TI  - Network legos: building blocks of cellular wiring diagrams.
AB  - Publicly available datasets provide detailed and large-scale information on
      multiple types of molecular interaction networks in a number of model organisms.
      The wiring diagrams composed of these interaction networks capture a static view
      of cellular state. An important challenge in systems biology is obtaining a
      dynamic perspective on these networks by integrating them with gene expression
      measurements taken under multiple conditions. We present a top-down computational
      approach to identify building blocks of molecular interaction networks by: (i)
      integrating gene expression measurements for a particular disease state (e.g.,
      leukemia) or experimental condition (e.g., treatment with growth serum) with
      molecular interactions to reveal an active network, which is the network of
      interactions active in the cell in that disease state or condition; and (ii)
      systematically combining active networks computed for different experimental
      conditions using set-theoretic formulae to reveal network legos, which are
      modules of coherently interacting genes and gene products in the wiring diagram.
      We propose efficient methods to compute active networks, systematically mine
      candidate legos, assess the statistical significance of these candidates, arrange
      them in a directed acyclic graph (DAG), and exploit the structure of the DAG to
      identify true network legos. We describe methods to assess the stability of our
      computations to changes in the input and to recover active networks by composing
      network legos. We analyze two human datasets using our method. A comparison of
      three leukemias demonstrates how a biologist can use our system to identify
      specific differences between these diseases. A larger-scale analysis of 13
      distinct stresses illustrates our ability to compute the building blocks of the
      interaction networks activated in response to these stresses. Source code
      implementing our algorithms is available under version 2 of the GNU General
      Public License at http://bioinformatics.cs.vt.edu/ murali/software/network-lego.

PMID- 18707559
TI  - The Peoples-uni: public health education for all.

PMID- 18707560
TI  - Cancer adds further urgency to prioritising obesity control.

PMID- 18707561
TI  - Development and validation of fall risk screening tools for use in residential
      aged care facilities.
AB  - OBJECTIVE: To develop screening tools for predicting falls in nursing home and
      intermediate-care hostel residents who can and cannot stand unaided. DESIGN AND
      SETTING: Prospective cohort study in residential aged care facilities in northern
      Sydney, New South Wales, June 1999-June 2003. PARTICIPANTS: 2005 people aged 65
      104 years (mean +/- SD, 85.7+/-7.1 years). MAIN OUTCOME MEASURES: Demographic,
      health, and physical function assessment measures; number of falls over a 6-month
      period; validity of the screening models. RESULTS: Ability to stand unaided was
      identified as a significant event modifier for falls. In people who could stand
      unaided, having either poor balance or two of three other risk factors (previous
      falls, nursing home residence, and urinary incontinence) increased the risk of
      falling in the next 6 months threefold (sensitivity, 73%; specificity, 55%). In
      people who could not stand unaided, having any one of three risk factors
      (previous falls, hostel residence, and using nine or more medications) increased
      the risk of falling twofold (sensitivity, 87%; specificity, 29%). CONCLUSIONS:
      These two screening models are useful for identifying older people living in
      residential aged care facilities who are at increased risk of falls. The screens
      are easy to administer and contain items that are routinely collected in
      residential aged care facilities in Australia.

PMID- 18707562
TI  - Incidence of bariatric surgery and postoperative outcomes: a population-based
      analysis in Western Australia.
AB  - OBJECTIVE: To investigate the incidence of bariatric surgery and postoperative
      outcomes in a population-based cohort of patients in Western Australia over a 17
      year period. DESIGN AND SETTING: A population-based incidence study of all
      bariatric procedures (n=1403) performed in WA hospitals over the period 1988
      2004, based on hospital morbidity and death data from the WA Data Linkage System.
      MAIN OUTCOME MEASURES: Changes in incidence of bariatric procedures over time;
      mortality and complications within 30 days after surgery; survival rates after
      surgery relative to age-, sex-, and period-matched survival rates in the general
      population; factors predictive of re-admission to hospital. RESULTS: The
      incidence of bariatric surgery increased from 1.2 procedures per 100,000 person
      years in 1988 to 24.2 procedures per 100,000 person-years in 2004. Although some
      of this was ascribed to a rising prevalence of obesity generally, there was a 13
      fold increase in the bariatric procedure rate within the obese population itself.
      At 5 years, the relative survival rate in bariatric patients was the same as the
      survival rate in the general population. Within the 30-day postoperative period,
      mortality was low (0.07%) and 9.6% of patients experienced complications. Those
      who had bypass-type procedures were more likely to be re-admitted within 30 days
      than those who had gastric reduction procedures (adjusted hazard ratio, 5.80 [95%
      CI, 3.42-9.84]). CONCLUSION: The use of bariatric surgery increased 20-fold over
      the study period. Relative survival after surgery was in line with population
      norms. The observed low mortality rates and moderate level of complications are
      similar to findings in other studies in which the proportion of reduction
      procedures has been high.

PMID- 18707563
TI  - Strongyloidiasis in personnel of the Regional Assistance Mission to Solomon
      Islands (RAMSI).
AB  - OBJECTIVE: To investigate the first reported cases of strongyloidiasis in the
      Solomon Islands, and to establish whether this disease poses a risk to personnel
      of the Regional Assistance Mission to Solomon Islands (RAMSI). DESIGN, SETTING
      AND PARTICIPANTS: Retrospective review of the pathology database of the RAMSI
      Medical Facility in Honiara, Solomon Islands, for the period 1 July 2006-30
      September 2007. MAIN OUTCOME MEASURES: Number and clinical features of confirmed
      cases of Strongyloides stercoralis infestation, as diagnosed by serological tests
      or faecal microscopy. RESULTS: Fourteen confirmed cases of strongyloidiasis in
      previously healthy RAMSI participants were identified. Of 13 patients with notes
      available, symptoms documented at presentation included epigastric pain (10
      patients), diarrhoea (7) and urticaria (4). Clinical disease in all patients
      responded to oral antihelminthic therapy (albendazole or ivermectin).
      CONCLUSIONS: Strongyloidiasis is endemic in the Solomon Islands and a risk for
      RAMSI personnel. Australian medical professionals should be aware of this
      potentially fatal and lifelong infestation, particularly the importance of an
      occupation history, appropriate diagnostic tests, effective treatment and
      adequate follow-up to document cure. We recommend implementation of a
      postdeployment screening program for strongyloidiasis.

PMID- 18707564
TI  - Financial disclosure and clinical research: what is important to participants?
AB  - OBJECTIVE: To assess what participants in company-sponsored clinical trials wish
      to know about financial aspects of the study. DESIGN, SETTING AND PARTICIPANTS:
      Cross-sectional questionnaire administered to 324 participants in six clinical
      trials conducted at the Royal Melbourne Hospital in 1999-2000 and 2006 for non
      acute conditions (asthma, chronic obstructive pulmonary disease, osteoporosis,
      rheumatoid arthritis, diabetes and influenza vaccine efficacy). MAIN OUTCOME
      MEASURES: Participants' desire for information on study funding, investigators'
      conflicts of interest, and use of accrued funds. RESULTS: 259 participants (80%)
      completed the survey. Participants wanted to be informed about the identity of
      the project sponsor (148 participants; 57%), whether the investigators owned
      shares in the company (105; 41%) or received travel grants (83; 32%), how much
      funding was accrued at study completion (88; 34%), how accrued funds were used
      (98; 38%), and who approved their use (91; 35%). After adjusting for year of
      survey and level of education, younger subjects (aged <or= 60 years) wished to be
      informed more often than older participants of who sponsored the project (odds
      ratio [OR], 2.35 [95% CI, 1.21-4.55]; P=0.012), whether the investigators owned
      shares in the company (OR, 2.41 [95% CI, 1.27-4.60]; P=0.007) and how much
      funding was available for other uses (OR, 1.79 [95% CI, 0.94-3.41]; P=0.078).
      CONCLUSION: While most participants indicated that they would take part in
      clinical research again regardless of whether they received financial
      information, providing information on the sponsor, the investigators' financial
      interest in the company, whether accrual of funds is expected, and how these
      funds will be spent should satisfy the interests of participants in company
      sponsored clinical trials.

PMID- 18707565
TI  - Public perceptions of Australia's doctors, hospitals and health care systems.
AB  - OBJECTIVE: To assess public perceptions of Australia's doctors, hospitals and
      health care systems. DESIGN AND PARTICIPANTS: A cross-sectional national
      telephone survey of a random sample of 800 Australian adults in August 2007. MAIN
      OUTCOME MEASURES: Ratings of subjective trust in health care providers, public
      and private hospitals, private health insurers and Medicare; attitudinal ratings
      for the current health care system, and public and private health care systems.
      RESULTS: Australians reported high trust in doctors (general practitioners more
      than specialists), low trust in alternative practitioners, moderate trust in
      hospitals (private more than public), and greater trust in Medicare than in
      private health insurers. Older adults had the greatest trust in physicians,
      hospitals and Medicare, but all age groups held similar attitudes toward public
      and private health care systems. Support for the current health care system with
      its mix of public and private funding was moderately strong, but all respondents
      reported weak pro-private attitudes and very strong pro-public attitudes.
      CONCLUSIONS: Public perceptions of Australian medical professionals, institutions
      and systems are generally positive. This sample did not endorse an individual
      user-pays private health system, but strongly favoured a universal public health
      system that is collectively funded by the public purse.

PMID- 18707566
TI  - How do Australian patients rate their general practitioner? A descriptive study
      using the General Practice Assessment Questionnaire.
AB  - OBJECTIVE: To report patient responses to the General Practice Assessment
      Questionnaire (GPAQ) as a measure of satisfaction with health care received from
      Australian general practitioners. DESIGN, SETTING AND PARTICIPANTS: A clustered
      cross-sectional study involving general practice patients from 30 randomly
      selected general practices in Victoria. Between January and December 2005, a
      screening survey, including a postal version of the GPAQ, was mailed to 17 780
      eligible patients. MAIN OUTCOME MEASURE: Scores on the six GPAQ items. RESULTS:
      We analysed data from 7130 patients who completed the screening survey and
      fulfilled our eligibility criteria. Levels of patient satisfaction with general
      practice care were generally high: mean GPAQ scores ranged from 68.6 (95% CI,
      66.1-71.0) for satisfaction with access to the practice to 84.0 (95% CI, 82.2
      85.4) for satisfaction with communication. Intracluster correlations for the GPAQ
      items ranged from 0.016 for overall satisfaction with the practice to 0.163 for
      satisfaction with access to the practice. Compared with national benchmarks in
      the United Kingdom, the GPs and practices participating in our study were rated
      higher on all six GPAQ items. Multivariable mixed effects linear regression
      showed that patients who were older, rated their health more highly, visited
      their GP more frequently and saw the same GP each time tended to express greater
      satisfaction with their care. CONCLUSION: Generally patients reported high levels
      of satisfaction with GP care. Greater satisfaction with care was associated with
      older patients, good health, more frequent contact with the GP, and seeing the
      one GP consistently.

PMID- 18707567
TI  - Fixing the problems that beset the Australian hospital system.
AB  - Public hospitals need an injection of cash to help reduce demand for hospital
      services; networking and role delineation among hospitals would immediately
      increase safety and quality.

PMID- 18707568
TI  - Primary health care reform: equity is the key.
AB  - Equity must be the basis of primary health care if reform is to deliver the
      outcomes we all want.

PMID- 18707569
TI  - Why we need a national registry in interventional cardiology.
AB  - Percutaneous coronary intervention (PCI) is increasingly used in the management
      of acute coronary syndromes and refractory angina, and technical advances such as
      drug-eluting stents (DES) and potent antithrombotic therapies (such as
      clopidogrel and glycoprotein IIb/IIIa inhibitors) have been heralded as improving
      long-term outcomes. Offsetting these advances has been: considerable concern
      about the safety of DES in regard to late stent thrombosis and antithrombotic
      drug-induced bleeding; the rising use of PCI and DES in clinical situations where
      evidence of efficacy is lacking; preferential use of PCI in low-risk populations;
      and limited cost-effectiveness data comparing PCI with other treatments. There
      are few contemporary data in Australia on the efficacy, safety and costs of PCI-
      as used in everyday clinical practice--that matches clinical outcomes with
      baseline patient characteristics, indications for intervention, coronary anatomy,
      procedural technique, co-interventions and site of care. A national registry that
      prospectively collects standardised data on processes and outcomes of PCI is
      warranted. This would ensure safe and appropriate evidence-based use of limited
      resources in an era of expanding use of PCI in clinical circumstances not tested
      in randomised trials.

PMID- 18707570
TI  - Bilateral renal halo sign in acute pancreatitis.

PMID- 18707571
TI  - Very late stent thrombosis after discontinuation of clopidogrel therapy.
AB  - Stent thrombosis is an infrequent but severe complication after coronary stent
      implantation. Dual antiplatelet therapy has markedly reduced the occurrence of
      this potentially catastrophic event. The optimal duration of clopidogrel therapy
      in patients with drug-eluting stents is unknown. We describe a case of stent
      thrombosis 9 days after discontinuation of clopidogrel therapy, more than 3 years
      after placement of drug-eluting stents.

PMID- 18707572
TI  - Colorectal cancer screening: ensuring benefits outweigh the risks.

PMID- 18707573
TI  - Effect of community consultation on recruitment of Indigenous women to a human
      papillomavirus prevalence study.

PMID- 18707574
TI  - Medical school selection criteria and the prediction of academic performance.

PMID- 18707575
TI  - Comparison of crystalline methamphetamine ("ice") users and other patients with
      toxicology-related problems presenting to a hospital emergency department.

PMID- 18707576
TI  - Selecting medical students.

PMID- 18707577
TI  - Encouraging general practitioners to train medical students.

PMID- 18707578
TI  - Teenage smoking in pregnancy and birthweight: a population study, 2001-2004.

PMID- 18707579
TI  - Preventing primary liver cancer: how well are we faring towards a national
      hepatitis B strategy?

PMID- 18707580
TI  - Health services under siege: the case for clinical process redesign.

PMID- 18707581
TI  - Evolution of cell interactions with extracellular matrix during carcinogenesis.
AB  - Interaction of cells with extracellular matrix (ECM) largely defines migration
      capacity of cells and ways of their dissemination in normal tissue processes and
      during tumor progression. We review current knowledge about structure of cell
      adhesions with ECM and their alterations during carcinogenesis. We analyze how
      changes in structure of cell-matrix adhesions and ECM itself lead to acquisition
      of neoplastic properties by cells. Modern concepts of tumor cell motility and
      changes in the relationships of cells with ECM during tumor development are
      presented. Contemporary approaches for influencing the cell-ECM adhesion
      structures for inhibition of invasion and metastasis are briefly discussed.

PMID- 18707582
TI  - Changes in regulation of cell-cell adhesion during tumor transformation.
AB  - Cadherin-mediated cell-cell adhesion defines the integrity of most tissues. Cell
      cell adherens junctions are dynamic structures whose functional state is
      regulated by interactions of cadherin with beta-catenin, p120, and actin
      cytoskeleton structures. Small GTPases of the Rho family and GTPase Rap1 play the
      central role in the formation and maintenance of cell-cell adhesion. Aberrant
      activation of signaling pathways, transcriptional repression of the E-cadherin
      gene, ectopic expression of N-cadherin, and disturbances in regulation of
      adhesive and transcriptional functions of beta-catenin stimulate tumor
      progression.

PMID- 18707583
TI  - Mechanisms of angiogenesis.
AB  - Tissue activity of angiogenesis depends on the balance of many stimulating or
      inhibiting factors. The key signaling system that regulates proliferation and
      migration of endothelial cells forming the basis of any vessel are vascular
      endothelium growth factors (VEGF) and their receptors. The VEGF-dependent
      signaling system is necessary for formation of the embryonic vascular system.
      Neoangiogenesis during tumor growth is also associated with activation of this
      signaling system. The biological significance of the effect of such system on the
      cells depends on the content in tissue of various factors of the VEGF family and
      their receptors, while in the case of VEGFA it is defined by the ratio of
      different isoforms of this growth factor. A number of other signaling systems are
      also involved in regulation of the main steps of vessel formation. The signaling
      system Dll4/Notch regulates selection of endothelial cells for beginning of
      angiogenic expansion by endowing particular properties to endothelial cells
      leading in this process. An important step in vessel stabilization and maturation
      is vascular wall formation. Signaling system PDGFB/PDGFRbeta as well as
      angiopoietins Ang1, Ang2, and their receptor Tie2 are involved in recruiting
      mural cells (pericytes and smooth muscle cells). Identification of key molecules
      involved in the regulation of angiogenesis may provide new possibilities for
      development of drugs suitable for inhibition of angiogenesis or its stimulation
      in various pathologies.

PMID- 18707584
TI  - Carcinogenesis induced by foreign bodies.
AB  - This review deals with the contemporary investigations of carcinogenesis induced
      by foreign bodies. The main attention is given to the interactions of macrophages
      with an implanted foreign body and their possible role in tumorigenesis.

PMID- 18707585
TI  - Affinity purification of a siderophore that exhibits an antagonistic effect
      against soft rot bacterium.
AB  - Bacterial colonies were isolated from different Egyptian soil samples. From these
      isolates, one bacterial species was found to produce siderophore. Using classical
      and biochemical identification methods, the siderophore producing isolate was
      identified as Pseudomonas fluorescens. Based on the affinity of siderophores for
      metal ions, an affinity chromatography system was designed for the purification
      of the siderophore in one step. It was possible to isolate 25 mg siderophore per
      liter of culture media. The purified siderophore was found to exist in two forms
      of approximately 30 and 90 kD. They are believed to be polymers of several
      siderophore molecules. Both forms were found to be active against the pathogen
      Erwinia carotovora var. carotovora, the causal bacteria of soft rot disease on
      potato tubers. The advantage of this method over other purification methods is
      that it uses metal ion so it can be applied for the purification of the known
      types of siderophores. Moreover, the purification is based on affinity
      chromatography, so the siderophore purity state permits several biotechnological
      applications without further treatments.

PMID- 18707586
TI  - Oxidative stress as regulatory factor for fatty-acid-induced uncoupling involving
      liver mitochondrial ADP/ATP and aspartate/glutamate antiporters of old rats.
AB  - Palmitate-induced uncoupling, which involves ADP/ATP and aspartate/glutamate
      antiporters, has been studied in liver mitochondria of old rats (22-26 months)
      under conditions of lipid peroxidation and inhibition of oxidative stress by
      antioxidants--thiourea, Trolox, and ionol. It has been shown that in liver
      mitochondria of old rats in the absence of antioxidants and under conditions of
      overproduction of conjugated dienes, the protonophoric uncoupling activity of
      palmitate is not suppressed by either carboxyatractylate or aspartate used
      separately. However, the combination of carboxyatractylate and aspartate
      decreased uncoupling activity of palmitate by 81%. In this case, palmitate
      induced uncoupling is limited by a stage insensitive to both carboxyatractylate
      and aspartate. In the presence of antioxidants, the palmitate-induced
      protonophoric uncoupling activity is suppressed by either carboxyatractylate or
      aspartate used separately. Under these conditions, palmitate-induced uncoupling
      is limited by a stage sensitive to carboxyatractylate (ADP/ATP antiporter) or
      aspartate (aspartate/glutamate antiporter). In the absence of antioxidants, the
      uncoupling activity of palmitate is not suppressed by ADP either in the absence
      or in the presence of aspartate. However, in the presence of thiourea, Trolox, or
      ionol ADP decreased the uncoupling activity of palmitate by 38%. It is concluded
      that in liver mitochondria of old rats the development of oxidative stress in the
      presence of physiological substrates of ADP/ATP and aspartate/glutamate
      antiporters (ADP and aspartate) results in an increase of the protonophoric
      uncoupling activity of palmitate.

PMID- 18707587
TI  - Implication of alpha5beta1 integrin in invasion of drug-resistant MCF-7/ADR
      breast carcinoma cells: a role for MMP-2 collagenase.
AB  - Expression of alpha5beta1 integrin in the drug-resistant MCF-7/ADR breast
      carcinoma cells was inhibited by treatment of these cells with alpha5-specific
      siRNA. The decrease of alpha5beta1 expression resulted in a sharp decrease of
      expression of MMP-2 collagenase and inhibition of invasion activity of these
      cells in vitro. Similar decrease of invasion was also observed during inhibition
      of MMP-2 expression by treatment of these cells with MMP-2-specific siRNA.
      Inhibition of alpha5beta1 expression was also accompanied by significant decrease
      in cell content of active (phosphorylated) forms of signal protein kinases Akt
      and Erk1/2. Inhibition of activity of these kinases by treatment of cells with PI
      3K/Akt-specific inhibitor LY294002 or Erk-specific inhibitor PD98059 resulted in
      inhibition of MMP-2 expression and the decrease of invasion in vitro. These data
      suggest that alpha5beta1 controls invasion ability of these cells by regulating
      expression of MMP-2, which involves PI-3K and Erk1/2 protein kinase signaling.

PMID- 18707588
TI  - Localization of Mullerian inhibiting substance receptors in various human cancer
      cell lines.
AB  - Recombinant human MIS (rhMIS) produced in transfected Chinese hamster ovary cells
      has been purified by immunoaffinity chromatography. In the absence of reducing
      agents, 140 kD homodimer and several oligomers with molecular masses from 280 to
      1000 kD are present. Homodimer, tetramer, and higher-molecular-weight rhMIS
      fractions reduced survival of tumor cells. For these experiments, FITC-labeled
      rhMIS was used for binding and endocytosis studies by flow cytometry. Flow
      cytometry performed on MIS-sensitive cancer cell lines demonstrated specific
      binding of rhMIS. The majority of rhMIS receptors have cytosolic localization.
      Thus, the level of MIS receptors on the cell membrane was proportional to the
      content of MIS-binding proteins in the whole cell and defines a level of receptor
      mediated endocytosis. The immunopurified rhMIS caused significant growth
      inhibition of ovarian and prostate adenocarcinoma and melanoma human cell lines
      in inhibition assays.

PMID- 18707589
TI  - Engineering, expression, and purification of "soluble" human cytochrome
      P45017alpha and its functional characterization.
AB  - To engineer a "soluble" form of membrane-bound cytochrome P45017alpha (CYP17)--a
      key enzyme in steroid hormone biosynthesis--in the present work we have built a
      computer model of the tertiary structure of the hemeprotein, identified the
      surface hydrophobic amino acid residues, substituted these residues for more
      hydrophilic ones, and expressed and purified hydrophilized forms of CYP17. We
      have constructed and purified the following mutant forms of human CYP17: CYP17dH
      (CYP17 with deleted hydrophobic N-terminal sequence (Delta(23))) and CYP17mod
      (CYP17dH with substituted cluster of hydrophobic amino acid residues in the
      region of the FG-loop). Removal of the N-terminal sequence responsible for
      interaction with the membrane does not dramatically change the association of the
      protein with the membrane. However, CYP17mod containing hydrophilic FG-loop is
      mostly localized in the cytosolic fraction. Thus, in the present work we for the
      first time engineered a "soluble" form of the usually membrane-bound human CYP17
      that is not bound to membrane. The expression degree of CYP17mod is approximately
      900 nmol/liter of culture. The hemeprotein can be purified to apparent
      homogeneity without using detergents at any purification step. It is shown that
      replacement of hydrophobic amino acid residues in the FG-loop region does not
      change the metabolic profile during hydroxylation of steroids that is
      characteristic for wild type CYP17. Besides, the modification of the hemeprotein
      does not affect the affinity of CYP17 to steroid substrates. The engineered
      "soluble" form of human CYP17 is used as a subject for crystallization of the
      hemeprotein.

PMID- 18707590
TI  - Inducible lectins and plant resistance to pathogens and abiotic stress.
AB  - Lectin concentration (activity) increases in plant tissues upon infection by
      pathogens, in response to abiotic stress, as well as during growth and
      development of tissues. Such a broad range of events accompanied by accumulation
      of lectins is indicative of their involvement in regulation of integral processes
      in plant cells. Data concerning the role of lectins in regulation of oxidative
      stress and stress-induced cytoskeleton rearrangements are presented.

PMID- 18707591
TI  - Induction of beta-1,3-glucanase in callus cultures in vitro.
AB  - Sodium salicylate (NaSA) increased induction of both intracellular and
      extracellular beta-1,3-glucanases in calluses of campion and duckweed. NaSA
      concentrations from 30 to 100 mM were optimal for induction of intracellular
      glucanase in the campion callus, and for induction of extracellular glucanase the
      optimal concentration varied from 5 to 100 mM. The glucanase activity in the
      duckweed callus was lower than in the campion callus, and co-cultivation of the
      campion callus with Trichoderma harzianum mycelium increased the production of
      intracellular and extracellular beta-1,3-glucanases and polygalacturonase in the
      callus. Biosynthesis by T. harzianum of glucanases, extracellular
      polygalacturonase and xylanase, and of intracellular galactosidase was increased.
      The co-cultivation was accompanied by increased activity of intracellular acidic
      isoform of glucanase Glu-3 secreted by the callus cells into the medium, whereas
      NaSA activated in the callus culture the extracellular acidic isoform Glu-1 and
      extracellular basic isoform Glu-5. These data indicate the induction of these
      isoforms and the specificity of protective response of plant cells to different
      factors.

PMID- 18707592
TI  - Tolerance to antimicrobial agents and persistence of Escherichia coli and
      cyanobacteria.
AB  - Bacterial persistence is the tolerance of a small part of a cell population to
      bactericidal agents, which is attained by a suppression of important cell
      functions and subsequent deceleration or cessation of cell division. The growth
      rate is the decisive factor in the transition of the cells to the persister
      state. A comparative study of quickly growing Escherichia coli K-12 strain MC
      4100 and cyanobacteria Synechocystis sp. PCC 6803 and Anabaena variabilis ATCC
      29413 growing slowly was performed. The cyanobacterial cells, like E. coli cells,
      differed in sensitivity to antimicrobial substances depending on the growth
      phase. Carbenicillin inhibiting the synthesis of peptidoglycan, a component of
      the bacterial cell wall, and lincomycin inhibiting the protein synthesis gave
      rise to nucleoid decay in cells from exponential cultures of Synechocystis 6803
      and did not influence the nucleoids in cells from stationary cultures.
      Carbenicillin suppressed the growth of exponential cultures and had no effect on
      cyanobacterial stationary cultures. A suppression of Synechocystis 6803 growth in
      the exponential phase by lincomycin was stronger than in the stationary phase.
      Similar data were obtained with cyanobacterial cells under the action of H2O2 or
      menadione, an inducer of reactive oxygen species production. Slowly growing
      cyanobacteria were similar to quickly growing E. coli in their characteristics.
      Persistence is a characteristic feature of cyanobacteria.

PMID- 18707593
TI  - Eosinophilic esophagitis in children with celiac disease: new diagnostic and
      therapeutic dilemmas.

PMID- 18707594
TI  - Role of double balloon enteroscopy in obscure gastrointestinal bleeding.

PMID- 18707595
TI  - Should simulator use become mandatory in endoscopy training?

PMID- 18707596
TI  - Intrahepatic stones: is it a lifestyle disease?

PMID- 18707597
TI  - HIV and hepatitis C coinfection.
AB  - The significant burden of HIV/hepatitis C virus (HCV) coinfection is increasingly
      recognized worldwide, and in particular within the Asia-Pacific region.
      Individuals who are coinfected with both viruses are at risk from accelerated
      liver disease and consequently cirrhosis, liver failure, and hepatocellular
      carcinoma. In addition, coinfected individuals may have altered immunological
      responses to HAART and are at increased risk of highly active antiretroviral
      therapy (HAART)-related hepatotoxicity. Treatment for HCV infection in HIV
      infected individuals is with standard pegylated interferon and ribavirin therapy,
      and all HIV/HCV coinfected subjects should undergo suitability for HCV treatment
      assessment. Response rates to HCV therapy are generally 10-15% lower than in HCV
      monoinfection, and therapy may be complicated by issues of drug interactions and
      significant toxicity. However, greater understanding of baseline factors can
      contribute to better prediction of treatment outcome, and monitoring of on
      treatment virological responses increasingly allows individualization of therapy.
      Where possible, treatment of HCV is often advisable before HAART is required to
      avoid the issues of drug interactions on HCV therapy and the risk of HAART
      related hepatotoxicity. Early diagnosis of both HIV and HCV infection is
      essential to most effectively manage HIV-HCV-coinfected individuals. New
      therapies, including HCV protease and polymerase inhibitors, are in development
      and may widen therapeutic options for HIV-HCV-coinfected individuals into the
      future.

PMID- 18707599
TI  - Hepatic steatosis in chronic hepatitis B patients is associated with metabolic
      factors more than viral factors.
AB  - BACKGROUND AND AIMS: Hepatic steatosis is commonly seen in chronic hepatitis C
      (CHC) patients. It has been reported to be associated with both metabolic factors
      and viral factors, and affects the severity of fibrosis in CHC. However, the
      relationship between hepatic steatosis and chronic hepatitis B (CHB) is unclear.
      The aims of this study were to investigate the frequency of hepatic steatosis in
      CHB patients, to identify the factors associated with its presence, and assess
      the relationship between the stage of steatosis and the severity of fibrosis.
      METHODS: Medical records of 153 adult patients with CHB who had undergone a liver
      biopsy within the past 4 years were included in the study. RESULTS: Body mass
      index (BMI) and age of CHB patients with steatosis was significantly higher than
      the patients without steatosis (P < 0.05), as determined by the univariate
      analysis. Steatosis was found to correlate with the BMI values and alanine
      aminotransferase (ALT) levels, and ALT levels were associated with hepatitis B
      virus (HBV)-DNA levels and histology activity index (HAI) scores, stages of
      fibrosis were associated with the HAI score and HBV-DNA, as determined by the
      multivariate analysis. In contrast, there was no significant association between
      advanced stages of fibrosis and steatosis. CONCLUSION: Our data indicate that
      hepatic steatosis is more frequently present in CHB patients than in the general
      population. We hypothesize that steatosis in CHB patients may be due to metabolic
      factors and the ability of HBV to indirectly facilitate the development of
      steatosis. In the present study, steatosis in CHB patients was not found to be
      associated with the severity of fibrosis.

PMID- 18707600
TI  - Education and Imaging. Gastrointestinal: angioedema of the small bowel.

PMID- 18707598
TI  - Improving outcomes for operable pancreatic cancer: is access to safer surgery the
      problem?
AB  - Despite advances in the understanding and treatment of pancreatic cancer in the
      last two decades, there is a persisting nihilistic attitude among clinicians. An
      alarmingly high rate of under-utilization of surgical management for operable
      pancreatic cancer was recently reported in the USA, where more than half of
      patients with stage 1 operable disease and no other contraindications were not
      offered surgery as therapy, denying this group of patients a 20% chance of long
      term survival. These data indicate that a nihilistic attitude among clinicians
      may be a significant and reversible cause of the persisting high mortality of
      patients with pancreatic cancer. This article examines the modern management of
      pancreatic cancer, in particular, the advances in surgical care that have reduced
      the mortality of pancreatectomy to almost that of colonic resection, and outlines
      a strategy for improving outcomes for patients with pancreatic cancer now and in
      the future.

PMID- 18707601
TI  - Education and Imaging. Gastrointestinal: barium-induced acute appendicitis.

PMID- 18707602
TI  - Education and Imaging. Gastrointestinal: colonic spirochetosis.

PMID- 18707603
TI  - Education and Imaging. Hepatobiliary and pancreatic: isolated pancreatic
      metastases.

PMID- 18707604
TI  - Fracture force of tooth-tooth- and implant-tooth-supported all-ceramic fixed
      partial dentures using titanium vs. customised zirconia implant abutments.
AB  - OBJECTIVES: Tooth-coloured customised implant abutments and full ceramic
      supraconstructions thereon can be made of zirconia by computer-aided
      manufacturing (CAM). The aim of this study was to examine the potential limits of
      zirconia three-unit fixed partial dentures made on customised zirconia implant
      abutments in implant-tooth supported cases. MATERIAL AND METHODS: Rigidly mounted
      implants (XiVE-S diameter 3.8 mm; length 11 mm; Friadent, Germany) were placed in
      PMMA-moulds pairwise with human molars at a distance of 10 mm in groups #1 and
      #2. Control group #3 consisted of two molars without implant involvement.
      Beforehand all molar roots were covered with polyether (Impregum: 3 M Espe,
      Germany) to simulate periodontal mobility. The abutments in #1 were individually
      fabricated from CerconBase and luted on experimental titanium bases (both:
      DeguDent, Germany). In #2, industrially prefabricated titanium abutments
      (Friadent) were used. All molar teeth were provided with a circumferential
      chamfer preparation. Three-unit fixed partial dentures were fabricated from
      CerconBase/CerconKiss in a CAM-process (Material/devices: DeguDent) for all test
      groups (n=8/group). All fixed partial dentures were cemented with RelyXUnicem (3
      M Espe), thermomechanically loaded (TCML=1.2 x 10(6) x 50 N; 6000 x 5 degrees /55
      degrees) and fracture tested in a Universal Test Machine (UTM 1446: Zwick,
      Germany). RESULTS: None of the dentures failed during TCML, and the Cercon
      abutments showed no damage either to the bonding surface to titanium or to the
      ceramic itself. Two fixation screws in group #1 broke towards the end of TCML.
      Fracture test result (Median and 25-/75-Percentiles) were: #1 1190 (1046/2008),
      #2 991 (832/1402), #3 1331 (1224/1428). CONCLUSIONS: All restoration alternatives
      showed sufficient fracture resistance for posterior regions.

PMID- 18707605
TI  - Clinical efficacy of prophylactic strategy of long-term low-dose acyclovir for
      Varicella-Zoster virus infection after allogeneic peripheral blood stem cell
      transplantation.
AB  - Varicella-Zoster virus infection (VZV) has a high incidence post-allogeneic
      peripheral blood stem cell transplant (PBSCT). However, data regarding long-term
      acyclovir prophylaxis for VZV prevention are limited. We evaluated the clinical
      efficacy of long-term low-dose acyclovir prophylaxis for VZV infection after
      allogeneic PBSCT at the Princess Margaret Hospital (PMH), Canada and the
      Kyungpook National University Hospital (KNUH), Korea. The acyclovir prophylaxis
      regimen at PMH was acyclovir 400 mg/d orally until engraftment, and at KNUH was
      acyclovir 800 mg/d orally until immunosuppression discontinuation. Long-term
      acyclovir prophylaxis was given to 26/193 (14%) patients in the PMH group and
      73/79 (92%) patients in the KNUH group. In the PMH group, 42 cases (22%)
      developed VZV infection, while six cases (8%) had VZV infection in the KNUH group
      (p = 0.005). With a median of 26.5 months of follow-up, the incidences of VZV
      infection at one and two yr were 15.8% and 20.7% in the PMH group, and 2.5% and
      5.8% in the KNUH group, respectively (p = 0.001). By controlling the other
      potential risk factors for VZV infection in multivariate analysis, the use of
      long-term acyclovir was the only protective factor for VZV infection after
      allogeneic PBSCT (p = 0.04, hazard ratio = 0.296). Long-term use of acyclovir
      appears to be protective for VZV infection after allogeneic PBSCT, especially
      during the period of immunosuppressive therapy.

PMID- 18707606
TI  - Shaping of the lower jaw bone during growth of Nile tilapia Oreochromis niloticus
      and a Lake Victoria cichlid Haplochromis chilotes: a geometric morphometric
      approach.
AB  - East African cichlids have evolved feeding apparatus morphologies to adapt to
      diverse feeding environments. However, little is known about how the morphologies
      are formed during development. Here, we assessed the shape changes of the lower
      jaw bone during growth of the Nile tilapia Oreochromis niloticus and a Lake
      Victoria cichlid Haplochromis chilotes using geometric morphometric methods.
      'Early Juvenile to Late Juvenile' and 'Late Juvenile to Adult' transitions of the
      shape change during growth of both O. niloticus and H. chilotes were detected.
      The 'Early Juvenile to Late Juvenile' transition of the shape change in H.
      chilotes occurred slightly earlier than in O. niloticus. We also compared the
      shape changes during growth of the two cichlids. Principal component analysis
      showed both commonalities and differences in the morphological changes between
      the cichlids. Our data suggest that most shape change may have a similar pattern
      during the growth of O. niloticus and H. chilotes, and that the differences in
      adult shapes may be due to differences arising early in development, not to the
      difference of shape change during growth. These data provide a basis for
      understanding the developmental mechanisms underlying this adaptive trait of East
      African cichlids.

PMID- 18707607
TI  - Analysis of Sir2E in the cellular slime mold Dictyostelium discoideum: cellular
      localization, spatial expression and overexpression.
AB  - It has been reported that Dictyostelium discoideum encodes four silent
      information regulator 2 (Sir2) proteins (Sir2A-D) showing sequence similarity to
      human homologues of Sir2 (SIRT1-3). Further screening in a database revealed that
      D. discoideum encodes an additional Sir2 homologue (Sir2E). The amino acid
      sequence of Sir2E is not similar to those of SIRTs but is similar to those of
      proteins encoded by Giardia lamblia, Cryptosporidium hominis and Cryptosporidium
      parvum. Fluorescence of Sir2E-green fluorescent protein fusion protein was
      detected in the D. discoideum nucleus, indicating that Sir2E is a nuclear
      localizing protein. Reverse transcription-polymerase chain reaction and whole
      mount in situ hybridization analyses showed that D. discoideum expressed sir2E in
      amoebae in the growth phase and in prestalk cells in the developmental phase. D.
      discoideum overexpressing sir2E grew faster than the wild type. These results
      indicate that Sir2E plays important roles both in the growth phase and
      developmental phase of D. discoideum.

PMID- 18707608
TI  - Use of benzoate as an electron acceptor by Syntrophus aciditrophicus grown in
      pure culture with crotonate.
AB  - In methanogenic environments, the main fate of benzoate is its oxidization to
      acetate, H(2) and CO(2) by syntrophic associations of hydrogen-producing benzoate
      degraders and hydrogen-using methanogens. Here, we report the use of benzoate as
      an electron acceptor. Pure cultures of S. aciditrophicus simultaneously degraded
      crotonate and benzoate when both substrates were present. The growth rate was
      0.007 h(-1) with crotonate and benzoate present compared with 0.025 h(-1) with
      crotonate alone. After 8 days of incubation, 4.12 +/- 0.50 mM of cyclohexane
      carboxylate and 8.40 +/- 0.61 mM of acetate were formed and 4.0 +/- 0.04 mM of
      benzoate and 4.8 +/- 0.5 mM of crotonate were consumed. The molar growth yield
      was 22.7 +/- 2.1 g (dry wt) of cells per mol of crotonate compared with about
      14.0 +/- 0.1 g (dry wt) of cells per mol of crotonate when S. aciditrophicus was
      grown with crotonate alone. Cultures grown with [ring-(13)C]-benzoate and
      unlabelled crotonate initially formed [ring-(13)C]-labelled cyclohexane
      carboxylate. No (13)C-labelled acetate was detected. In addition to cyclohexane
      carboxylate, (13)C-labelled cyclohex-1-ene carboxylate was detected as an
      intermediate. Once almost all of the benzoate was gone, carbon isotopic analyses
      showed that cyclohexane carboxylate was formed from both labelled and non
      labelled metabolites. Glutarate and pimelate were also detected at this time and
      carbon isotopic analyses showed that each was made from a mixture labelled and
      non-labelled metabolites. The increase in molar growth yield with crotonate and
      benzoate and the formation of [ring-(13)C]-cyclohexane carboxylate from [ring
      (13)C]-benzoate in the presence of crotonate are consistent with benzoate serving
      as an electron acceptor.

PMID- 18707609
TI  - Identification and analysis of four candidate symbiosis genes from
      'Chlorochromatium aggregatum', a highly developed bacterial symbiosis.
AB  - The consortium 'Chlorochromatium aggregatum' currently represents the most highly
      developed interspecific association between prokaryotes. It consists of green
      sulfur bacteria, so-called epibionts, which surround a central, motile,
      chemotrophic bacterium. Four putative symbiosis genes of the epibiont were
      recovered by suppression subtractive hybridization and bioinformatics approaches.
      These genes are transcribed constitutively and do not occur in the free-living
      relatives of the epibiont. The haemagglutinin-like putative gene products of open
      reading frames (ORFs) Cag0614 and Cag0616 are unusually large and contain
      repetitive regions and RGD tripeptides. Cag0616 harbours two betagamma
      crystalline Greek key motifs. Cag1920 codes for a putative haemolysin whereas the
      gene product of Cag1919 is a putative RTX-like protein. Based on detailed
      analyses of Cag1919, the C-terminal amino acid sequence comprises six repetitions
      of the motif GGXGXD predicted to form a Ca(2+)-binding beta roll. Intact 'C.
      aggregatum' consortia disaggregated upon the addition of EGTA or pyrophosphate,
      but stayed intact in the presence of various lectine-binding sugars or
      proteolytic enzymes. Unlike other RTX toxins, a gene product of Cag1919 could not
      be detected by (45)Ca(2+) autoradiography, indicating a low abundance of the
      corresponding protein in the cells. The RTX-type C-terminus coded by Cag1919
      exhibited a significant similarity to RTX modules of various proteobacterial
      proteins, suggesting that this putative symbiosis gene has been acquired via
      horizontal gene transfer from a proteobacterium.

PMID- 18707610
TI  - The influence of soil pH on the diversity, abundance and transcriptional activity
      of ammonia oxidizing archaea and bacteria.
AB  - Autotrophic ammonia oxidation occurs in acid soils, even though laboratory
      cultures of isolated ammonia oxidizing bacteria fail to grow below neutral pH. To
      investigate whether archaea possessing ammonia monooxygenase genes were
      responsible for autotrophic nitrification in acid soils, the community structure
      and phylogeny of ammonia oxidizing bacteria and archaea were determined across a
      soil pH gradient (4.9-7.5) by amplifying 16S rRNA and amoA genes followed by
      denaturing gradient gel electrophoresis (DGGE) and sequence analysis. The
      structure of both communities changed with soil pH, with distinct populations in
      acid and neutral soils. Phylogenetic reconstructions of crenarchaeal 16S rRNA and
      amoA genes confirmed selection of distinct lineages within the pH gradient and
      high similarity in phylogenies indicated a high level of congruence between 16S
      rRNA and amoA genes. The abundance of archaeal and bacterial amoA gene copies and
      mRNA transcripts contrasted across the pH gradient. Archaeal amoA gene and
      transcript abundance decreased with increasing soil pH, while bacterial amoA gene
      abundance was generally lower and transcripts increased with increasing pH. Short
      term activity was investigated by DGGE analysis of gene transcripts in microcosms
      containing acidic or neutral soil or mixed soil with pH readjusted to that of
      native soils. Although mixed soil microcosms contained identical archaeal ammonia
      oxidizer communities, those adapted to acidic or neutral pH ranges showed greater
      relative activity at their native soil pH. Findings indicate that different
      bacterial and archaeal ammonia oxidizer phylotypes are selected in soils of
      different pH and that these differences in community structure and abundances are
      reflected in different contributions to ammonia oxidizer activity. They also
      suggest that both groups of ammonia oxidizers have distinct physiological
      characteristics and ecological niches, with consequences for nitrification in
      acid soils.

PMID- 18707611
TI  - Regulation of copper homeostasis in Pseudomonas fluorescens SBW25.
AB  - Copper is an essential element for life, but too much copper is harmful: copper
      homeostasis must therefore be carefully regulated. When growing on plant
      surfaces, the plant growth-promoting bacterium Pseudomonas fluorescens SBW25
      activates expression of a copper-transporting P1-type ATPase (CueA). Using a
      combination of transcriptional gene fusions and site-directed mutants, we show
      that copper-induced transcription of cueA is controlled by the MerR-type
      regulator, CueR; CueR is also required for activation of the copper chaperone
      protein encoded by cueZ (pflu0660). The promoters of cueA and cueZ are also
      responsive to the metal salts of gold, silver and mercury. In each case, CueR
      transduces the stimulus. Resistance to exogenously applied copper sulfate shows
      that cueA and cueR mutants are significantly less resistant than the wild type.
      This is consistent with the role of CueA as a copper efflux system and a general
      role for the CueR regulon in copper resistance. A search of the SBW25 genome for
      orthologues of genes predicted to play additional roles in copper homeostasis
      identified copCD of the known four-component copABCD system (unusually, copAB are
      absent from the SBW25 genome). Genetic studies showed that expression of copCD is
      controlled by copper and mediated by the CopRS two-component regulatory system.
      Mutants devoid of copCD or copS displayed an increased tolerance to copper and
      overexpression of copCD caused increased sensitivity. This is consistent with
      CopCD encoding a copper uptake system. Taken together, we suggest that the Cue
      and Cop systems are integral to copper homeostasis in P. fluorescens SBW25 with
      one (Cop) being active at low-copper environments and bringing copper into the
      cell, and the other (Cue) being active in high-copper environments and serving to
      export excess copper.

PMID- 18707613
TI  - A real-time polymerase chain reaction assay for quantitative detection of the
      human-specific enterococci surface protein marker in sewage and environmental
      waters.
AB  - A real-time polymerase chain reaction (PCR) assay using SYBR Green I dye was
      developed to quantify the Enterococcus faecium enterococci surface protein (esp)
      marker in sewage (n = 16) and environmental waters (n = 16). The concentration of
      culturable enterococci in raw sewage samples ranged between 1.3 x 10(5) and 5.6 x
      10(5) colony-forming units (cfu) per 100 ml. The real-time PCR detected 9.8 x
      10(3)-3.8 x 10(4) gene copies of the esp marker per 100 ml of sewage. However,
      the concentration of culturable enterococci and the esp marker in secondary
      effluent was two orders of magnitude lower than raw sewage. Surface water samples
      were collected from a non-sewered catchment after storm events and the real-time
      PCR was applied to quantify the esp marker. Of the 16 samples tested, 6 (38%)
      were PCR-positive and the concentration of the esp marker ranged between 1.1 x
      10(2) and 5.3 x 10(2) gene copies per 100 ml of water samples. The newly
      developed real-time PCR method was successfully used to quantify the esp marker
      in samples collected from sewage and environmental waters. The presence of the
      esp marker in water samples immediately after storm events not only indicated
      human faecal pollution but also provided evidence of the degree of human faecal
      pollution. To our knowledge, this is the first study that reports the use of a
      real-time PCR assay to quantify the esp marker in sewage and surface waters. Such
      study would provide valuable information for managers for the improved management
      of water quality.

PMID- 18707614
TI  - Predominance of Gram-positive bacteria in house dust in the low-allergy risk
      Russian Karelia.
AB  - Simple living conditions and farming environment have been associated with
      reduced risk for allergic diseases such as atopy and asthma but the factors
      responsible for this effect remain unresolved. We examined the bacterial
      composition of house dusts obtained from Finnish and Russian Karelia, two
      adjacent areas with high and low occurrence of atopic diseases respectively. Two
      dust mixes, both composed of 10 randomly selected dust samples from 349 Finnish
      and 417 Russian Karelian households were studied for bacterial biomarkers (DNA,
      Limulus-active endotoxin, 3-OH fatty acids, muramic acid) and for 16S rRNA gene
      sequences. Overall, the DNA cloning revealed more taxons (94 different genera) of
      dustborne bacteria than seen in any previous study on residential environments.
      Majority (67%) of the bacterial DNA clones in house dust from the low-allergy
      Russian Kareliarepresented Gram-positive bacteria (Firmicutes and
      Actinobacteria), predominantly Staphylococcaceae and Corynebacteriaceae. Russian
      Karelian dust showed up to 20-fold higher contents of muramic acid (marker of
      Gram-positive bacteria) and a sevenfold higher number of clones of animal
      associated species, whereas in Finnish Karelian dust Gram-negatives (mainly
      Proteobacteria) predominated. Clones of plant-associated bacterial species and of
      chloroplast, indicating plant biomass, were more numerous in Finnish than in
      Russian Karelian dust. In conclusion, this study revealed major disparities
      between Finnish and Russian house dusts. The higher bacterial content and the
      predominance of Gram-positive bacteria in Russian dust may have implications for
      occurrence of atopy.

PMID- 18707612
TI  - Global distribution and diversity of coral-associated Archaea and their possible
      role in the coral holobiont nitrogen cycle.
AB  - Diversity, distribution and genetic comparison of Archaea associated with the
      surface mucus of corals from three genera, namely Acanthastrea sp., Favia sp. and
      Fungia sp., from the Gulf of Eilat, Israel and from Heron Island, Australia were
      studied. Sequencing of the 16S rRNA gene of the coral-associated Archaea revealed
      dominance of Crenarchaeota (79%, on average). In this phylum, 87% of the
      sequences were similar (>or= 97%) to the Thermoprotei, with 76% of these being
      similar (>or= 97%) to the ammonium oxidizer, Nitrosopumilus maritimus. Most of
      the coral-associated euryarchaeotal sequences (69%) were related to marine group
      II, while other euryarchaeotal clades were found to be related to anaerobic
      methanotrophs (8%), anaerobic nitrate reducers (i.e. denitrification, 15%) and
      marine group III (8%). Most of the crenarchaeotal and euryarchaeotal coral
      associated 16S rRNA gene sequences from Heron Island (61%) and from the Gulf of
      Eilat (71%) were closely related (>or= 97%) to sequences previously derived from
      corals from the Virgin Islands. Analysis of archaeal amoA sequences obtained from
      the fungiid coral, Fungia granulosa, divided into three clades, all related to
      archaeal sequences previously obtained from the marine environment. These
      sequences were distantly related to amoA sequences previously found in
      association with other coral species. Preliminary experiments suggest that there
      is active oxidation of ammonia to nitrite in the mucus of F. granulosa. Thus,
      coral-associated Archaea may contribute to nitrogen recycling in the holobiont,
      presumably by acting as a nutritional sink for excess ammonium trapped in the
      mucus layer, through nitrification and denitrification processes.

PMID- 18707615
TI  - Systematic evaluation of single mismatch stability predictors for fluorescence in
      situ hybridization.
AB  - The mismatch discrimination potential of probes in fluorescence in situ
      hybridization can be defined as the difference between the melting formamide
      points of perfect complementary and mismatched duplexes (Delta[FA](m)). Using a
      combined experimental and theoretical approach, Delta[FA](m) was determined for a
      set of 35 mismatched probes targeting seven locations in the 16S rRNA of
      Escherichia coli. The mismatches were created by changing single nucleotides on
      the probes, while maintaining the target unmodified. Estimated Delta[FA](m)
      values were used to systematically evaluate four predictors of mismatch
      stability: weighted mismatch (WM) scores from the software arb, published
      statistical summary of microarray hybridizations, free energy of mismatch
      stability (DeltaDeltaG degrees (1)) and theoretical Delta[FA](m) estimations
      obtained with a thermodynamic model. Based on the predictors' ability to explain
      variability in Delta[FA](m) and to discriminate weak mismatches from strong ones,
      DeltaDeltaG degrees (1) and WM scores from arb (with an updated set of relative
      strength parameters) were demonstrated to be adequate estimators of mismatch
      stability, with DeltaDeltaG degrees (1) offering the benefit of capturing the
      variability associated with nearest-neighbour effects and being compatible with
      thermodynamic models of in situ hybridization. The use of DeltaDeltaG degrees (1)
      and WM in probe design was illustrated as a tool that complements experimental
      design approaches.

PMID- 18707616
TI  - Endosymbioses between bacteria and deep-sea siboglinid tubeworms from an Arctic
      Cold Seep (Haakon Mosby Mud Volcano, Barents Sea).
AB  - Siboglinid tubeworms do not have a mouth or gut and live in obligate associations
      with bacterial endosymbionts. Little is currently known about the phylogeny of
      frenulate and moniliferan siboglinids and their symbionts. In this study, we
      investigated the symbioses of two co-occurring siboglinid species from a methane
      emitting mud volcano in the Arctic Ocean (Haakon Mosby Mud Volcano, HMMV):
      Oligobrachia haakonmosbiensis (Frenulata) and Sclerolinum contortum (Monilifera).
      Comparative sequence analysis of the host-specific 18S and the symbiont-specific
      16S rRNA genes of S. contortum showed that the close phylogenetic relationship of
      this host to vestimentiferan siboglinids was mirrored in the close relationship
      of its symbionts to the sulfur-oxidizing gammaproteobacterial symbionts of
      vestimentiferans. A similar congruence between host and symbiont phylogeny was
      observed in O. haakonmosbiensis: both this host and its symbionts were most
      closely related to the frenulate siboglinid O. mashikoi and its
      gammaproteobacterial symbiont. The symbiont sequences from O. haakonmosbiensis
      and O. mashikoi formed a clade unaffiliated with known methane- or sulfur
      oxidizing bacteria. Fluorescence in situ hybridization indicated that the
      dominant bacterial phylotypes originated from endosymbionts residing inside the
      host trophosome. In both S. contortum and O. haakonmosbiensis, characteristic
      genes for autotrophy (cbbLM) and sulfur oxidation (aprA) were present, while
      genes diagnostic for methanotrophy were not detected. The molecular data suggest
      that both HMMV tubeworm species harbour chemoautotrophic sulfur-oxidizing
      symbionts. In S. contortum, average stable carbon isotope values of fatty acids
      and cholesterol of -43 per thousand were highly negative for a sulfur oxidizing
      symbiosis, but can be explained by a (13)C-depleted CO(2) source at HMMV. In O.
      haakonmosbiensis, stable carbon isotope values of fatty acids and cholesterol of 
      70 per thousand are difficult to reconcile with our current knowledge of isotope
      signatures for chemoautotrophic processes.

PMID- 18707617
TI  - 2007 Morris-Coole prize awarded to Nicola Marchi.

PMID- 18707618
TI  - An audit of follow-up clinics for breast cancer patients in Cornwall: is the time
      and effort worth it?
AB  - This paper's aims were to investigate the time and costs of healthcare
      professionals involved with follow-up clinics for breast cancer patients; and to
      quantify the numbers of local recurrences detected. An audit of breast cancer
      patients diagnosed with disease recurrence was conducted, and data were collected
      from the cancer audit system and from an analysis of relevant case notes. Costs
      of the time spent in follow-up clinics by clinical staff were also collected. The
      study found that sixty-nine breast cancer patients were diagnosed with local
      recurrence between 1 January 1999 and 31 December 2004. Only 15% (10) of
      recurrences were detected at routine follow up, 48% were first noticed by
      patients themselves, and 37% were detected at routine mammography. Six separate
      follow-up clinics were scheduled each week. This involved a total clinic time of
      approximately 20 h, and a total weekly cost of around pound 4857, with an annual
      cost of pound 252,564. Our recommendation is that alternative methods of follow
      up need to be implemented so that healthcare professionals have more time for
      newly diagnosed patients, those on active treatment and those with relapsed
      disease.

PMID- 18707619
TI  - Once-weekly epoetin beta therapy in patients with solid tumours and chemotherapy
      induced anaemia: a randomized, double-blind, dose-finding study.
AB  - Anaemia is common in patients receiving chemotherapy, causing symptoms that have
      a major impact on quality of life (QoL). Epoetin beta rapidly increases
      haemoglobin (Hb) levels and improves QoL in anaemic patients with a variety of
      tumours. This was a randomized, double-blind, parallel-group, dose-finding study
      assessing the efficacy and safety of once-weekly epoetin beta in patients with
      solid tumours receiving chemotherapy. Adult patients with anaemia (Hb < 11 g/dL)
      were randomized to receive epoetin beta 30,000 IU or 20,000 IU once weekly for 12
      weeks. All patients received oral iron supplementation. Haemoglobin levels,
      transfusion need and QoL [Functional Assessment of Cancer Therapy-fatigue (FACT
      F) subscale score] were assessed at regular intervals. Fifty patients were
      randomized; 30 patients received epoetin beta 30,000 IU once weekly and 20
      received 20,000 IU once weekly. Mean (+/- SD) increase in Hb from baseline to
      week 12 was 1.75 +/- 2.15 g/dL in the 30,000 IU group (P = 0.008 vs. baseline)
      and 1.04 +/- 1.75 g/dL in the 20,000 IU group (non-significant). Haemoglobin
      response (increase in Hb >or=2 g/dL from baseline) was observed in 78.3% of
      patients receiving epoetin beta 30,000 IU and 66.7% receiving epoetin beta 20,000
      IU. Improvements in FACT-F subscale score were significantly (P < 0.001)
      correlated with increases in Hb level. Transfusion use was low during the study
      in both groups. Both epoetin beta regiments were well tolerated and there were no
      dose-dependent adverse events. Epoetin beta 30,000 IU once weekly is an effective
      and well-tolerated treatment of anaemia in patients with solid tumours.

PMID- 18707620
TI  - Symptoms beyond diagnosis--a case study.
AB  - The aim of this paper was to discuss how words for symptoms relate to experience
      and to find out how seriously ill patients two years after diagnosis and
      treatment articulated suffering. Nine patients who have had a cancer tumour of
      the central nervous system were interviewed in their homes and the findings were
      interpreted in a hermeneutic process. Bodily, obstructive, emotive and
      metaphorical expressions of symptoms appeared. The transformed life situation
      involved inability to perform everyday tasks and a feeling of frustration of
      needs and desires. The words for symptoms conveyed individual embodied experience
      connected to a discourse of shared meanings. The relationship between
      individuality and culture means that words for symptoms are created and
      understood in a process between patient and listener, between discourse, culture
      and history.

PMID- 18707621
TI  - Effect of epoetin alpha therapy on cognitive function in anaemic patients with
      solid tumours undergoing chemotherapy.
AB  - The primary aim of this study was to assess whether epoetin alpha (Ea) would
      improve cognitive performance in a group of anaemic cancer patients receiving
      chemotherapy. The secondary aim was to confirm the positive impact of Ea on
      haematological parameters, and quality of life (QOL). Fifty patients with solid
      tumours and haemoglobin (Hb) <11.0 g/dL received Ea 40,000 units once weekly for
      12 weeks and were administered the Mini-Mental State Examination and the European
      Organization for Research and Treatment of Cancer (QLQ-C30) questionnaire prior
      to Ea therapy and at study completion. No clinically significant alterations were
      observed on cognitive function during Ea treatment. Changes in cognitive function
      were unrelated to Hb change and there were no significant differences in
      cognitive performance between Ea responders and non-responders. The analyses
      revealed clinically significant improvements in Hb levels, physical and role
      function, and clinically meaningful reductions in fatigue. Hb changes were
      significantly associated with the magnitude of improvement in QOL parameters. The
      lack of a clinical benefit in cognition observed in this study during Ea
      treatment may redirect the focus of research from enhancing to maintaining
      cognitive function, since stability in cognitive performance through time may be
      as well clinically important.

PMID- 18707622
TI  - Estimation of 16S rRNA gene copy number in several probiotic Lactobacillus
      strains isolated from the gastrointestinal tract of chicken.
AB  - The copy numbers of 16S rRNA genes in 12 probiotic Lactobacillus strains of
      poultry origin were analyzed. Genomic DNA of the strains was digested with
      restriction endonucleases that do not cut within the 16S rRNA gene of the
      strains. This was followed by Southern hybridization with a biotinylated probe
      complementary to the 16S rRNA gene. The copy number of the 16S rRNA gene within a
      Lactobacillus species was found to be conserved. From the hybridization results,
      Lactobacillus salivarius I 24 was estimated to have seven copies of the 16S rRNA
      gene, Lactobacillus panis C 17 to have five copies and Lactobacillus gallinarum
      strains I 16 and I 26 four copies. The 16S rRNA gene copy numbers of L.
      gallinarum and L. panis reported in the present study are the first record.
      Lactobacillus brevis strains I 12, I 23, I 25, I 211, I 218 and Lactobacillus
      reuteri strains C 1, C 10, C 16 were estimated to have at least four copies of
      the 16S rRNA gene. In addition, distinct rRNA restriction patterns which could
      discriminate the strains of L. reuteri and L. gallinarum were also detected.
      Information on 16S rRNA gene copy number is important for physiological,
      evolutionary and population studies of the bacteria.

PMID- 18707623
TI  - Distribution of Archaea in Japanese patients with periodontitis and humoral
      immune response to the components.
AB  - There is controversy regarding the existence of archaeal pathogens. Periodontitis
      is one of the human diseases in which Archaea have been suggested to have roles
      as pathogens. This study was performed to investigate the distribution of Archaea
      in Japanese patients with periodontitis and to examine the serum IgG responses to
      archaeal components. Subgingival plaque samples were collected from 111
      periodontal pockets of 49 patients (17 with aggressive periodontitis and 32 with
      chronic periodontitis), and 30 subgingival plaque samples were collected from 17
      healthy subjects. By PCR targeting the 16S rRNA gene, Archaea were detected in 15
      plaque samples (13.5% of total samples) from 11 patients (29.4% of patients with
      aggressive periodontitis and 18.8% of patients with chronic periodontitis).
      Archaea were detected mostly (14/15) in severe diseased sites (pocket depth > or
      =6 mm), while no amplicons were observed in any samples from healthy controls.
      Sequence analysis of the PCR products revealed that the majority of Archaea in
      periodontal pockets were a Methanobrevibacter oralis-like phylotype. Western
      immunoblotting detected IgG antibodies against M. oralis in eight of the 11 sera
      from patients. These results suggest the potential of Archaea (M. oralis) as an
      antigenic pathogen of periodontitis.

PMID- 18707624
TI  - Membrane topology of the Salmonella enterica serovar Typhimurium Group B O
      antigen translocase Wzx.
AB  - The O-antigen translocase, Wzx, is involved in translocation of bacterial
      polysaccharide repeat units across the cytoplasmic membrane, and is an unusually
      diverse, highly hydrophobic protein, with high numbers of predicted alpha-helical
      transmembrane segments (TMS). The Salmonella enterica serovar Typhimurium Group B
      O-antigen Wzx was an ideal candidate for topological study as the O-antigen gene
      cluster is one of only a few that have been well characterized. The topology
      profile prediction for this protein was determined using five programs, with
      different recognition parameters, which consistently predict that 12 TMS are
      present. A membrane topology model was constructed by analysis of lacZ and phoA
      gene fusions at randomly selected and targeted fusion sites within wzx. Enzyme
      activity of these, and full-length C-terminal fusion proteins, confirmed the 12
      TMS topology for this Wzx, and also indicated that the C-terminus was located
      within the cytoplasm, which is consistent with the predicted topology.

PMID- 18707625
TI  - Cloning and functional identification of C-4 methyl sterol oxidase genes from the
      penicillin-producing fungus Penicillium chrysogenum.
AB  - Two C-4 methyl sterol oxidase genes (Pcerg25A and Pcerg25B) that are involved in
      ergosterol biosynthesis have been cloned from the penicillin-producing fungus
      Penicillium chrysogenum. cDNAs of both Pcerg25A and Pcerg25B have an ORF 885 bp
      in length, encoding a peptide of 295 residues. The deduced amino acid sequences
      of PcErg25A and PcErg25B show 86% identity, and have high identities to the
      characterized C-4 methyl sterol oxidases from Candida albicans and Saccharomyces
      cerevisiae. The function of Pcerg25A and Pcerg25B was identified by
      complementation of a yeast erg25-deficient strain. Pcerg25A is located in the DNA
      region containing the penicillin gene cluster, and thus its copy number is
      dependent on the patterns of the cluster region. Up to eight copies of Pcerg25A
      were found in the high-productivity strain NCPC 10086. By contrast, Pcerg25B was
      present in just a single copy in all tested P. chrysogenum genomes. Differences
      in the transcript level of either Pcerg25A or Pcerg25B were observed in different
      P. chrysogenum strains by real-time quantitative reverse transcriptase PCR
      analysis.

PMID- 18707626
TI  - The occurrence of porosity in reline acrylic resins. Effect of microwave
      disinfection.
AB  - BACKGROUND: Microwave energy has proved to be an effective method for
      disinfecting acrylic dentures. However, the effect of microwave heating on the
      porosity of autopolymerising denture reline resins has not been investigated.
      OBJECTIVE: The purpose of the study was to determine the effect of microwave
      disinfection on the porosity of autopolymerised denture reline materials
      (Kooliner-K, New Truliner-NT, Tokuso Rebase Fast-TR and Ufi Gel Hard-UGH) and a
      conventional heat-polymerised denture base resin (Lucitone 550-L). MATERIAL AND
      METHODS: Specimens (10 mm x 20 mm x 1 mm) were obtained from the impression
      surface of the palatal mucosa in a single person and divided into four groups (n
      = 5). The porosity was evaluated after polymerisation (C1), after two cycles of
      microwave disinfection (MW2), after seven cycles of microwave disinfection (MW7)
      and after 7 days storage in water at 37 degrees C (C2). Specimens from group MW7
      were exposed to microwave disinfection daily being stored in water at 37 degrees
      C between exposures. All the replicas were sputter coated with gold and
      micrographs/digital images were taken of each replica using scanning electron
      microscopy at magnification x 100. The SEM micrographs were then examined using
      an image analyser to determine the number of pores. Comparison between materials
      and groups were made using Kruskal-Wallis tests. RESULTS: MW7 resulted in a
      significant increase in the number from the pores of material K, but decreased in
      number in reline material TR and UGH reline resin. The number of pores in
      materials NT and L remained unaffected following microwave disinfection.
      CONCLUSION: Differences in the porosity amongst the materials and for different
      experimental conditions were observed following microwave disinfection.

PMID- 18707627
TI  - TMD and GOHAI indices of Brazilian institutionalised and community-dwelling
      elderly.
AB  - RATIONALE AND OBJECTIVES: Considering the controversy in the literature regarding
      several aspects of temporomandibular dysfunction (TMD) in elderly populations and
      the absence of reliable data on elderly Brazilians in this field, this study
      consisted of an evaluation of TMD prevalence and the self-perception of oral
      health among institutionalised and community-dwelling elderly in Sao Jose dos
      Campos, Brazil. METHODS: Two hundred and fifteen community-dwelling and 185
      institutionalised elderly people were evaluated by the Helkimo anamnestic (Ai)
      and clinical dysfunction (Di) indices and answered a questionnaire using the
      Geriatric Oral Health Assessment Index (GOHAI). RESULTS: The major prevalence of
      TMD symptoms was for the Ai0 (symptom-free) group (69.5%), while the major
      prevalence of clinical signs was for the DiI (mild) group (56%). Women presented
      a higher AiII classification than men (chi(2) test, p = 0.049). Community
      dwelling elderly presented a significantly lower Ai0 classification than the
      institutionalised ones (Two ratios equality test, p < 0.001). There was no
      relationship between the institutionalised status and the clinical dysfunction
      index for Di0 and DiIII classification (Two ratios equality test, p = 0.194 and
      0.535 respectively). The institutionalised elderly presented greater (One-way
      ANOVA = 0.005) self-perception of oral health (33.45) than did the community
      dwelling group (32.66). There were only weak Pearson's correlations among the
      anamnestic (-33.0%) or clinical (-14.7%) findings by the TMD and GOHAI indices.
      Symptom-free (Ai0) institutionalised elderly presented better scores in all GOHAI
      dimensions and elderly representing an absence of clinical TMD signs (Di0)
      presented higher GOHAI physical dimension scores in both groups. CONCLUSIONS: The
      prevalence of TMD symptoms among this sample of elderly individuals was
      relatively low, self-perception of oral health was reasonable and a weak, inverse
      correlation was found between TMD signs and symptoms and elderly self-perception
      of oral health measured by the GOHAI index.

PMID- 18707628
TI  - Clinical practice guideline: cerumen impaction.
AB  - OBJECTIVE: This guideline provides evidence-based recommendations on managing
      cerumen impaction, defined as an accumulation of cerumen that causes symptoms,
      prevents assessment of the ear, or both. We recognize that the term "impaction"
      suggests that the ear canal is completely obstructed with cerumen and that our
      definition of cerumen impaction does not require a complete obstruction. However,
      cerumen impaction is the preferred term since it is consistently used in clinical
      practice and in the published literature to describe symptomatic cerumen or
      cerumen that prevents assessment of the ear. This guideline is intended for all
      clinicians who are likely to diagnose and manage patients with cerumen impaction.
      PURPOSE: The primary purpose of this guideline is to improve diagnostic accuracy
      for cerumen impaction, promote appropriate intervention in patients with cerumen
      impaction, highlight the need for evaluation and intervention in special
      populations, promote appropriate therapeutic options with outcomes assessment,
      and improve counseling and education for prevention of cerumen impaction. In
      creating this guideline the American Academy of Otolaryngology-Head and Neck
      Surgery Foundation selected a panel representing the fields of audiology, family
      medicine, geriatrics, internal medicine, nursing, otolaryngology-head and neck
      surgery, and pediatrics. RESULTS: The panel made a strong recommendation that 1)
      clinicians should treat cerumen impaction that causes symptoms expressed by the
      patient or prevents clinical examination when warranted. The panel made
      recommendations that 1) clinicians should diagnose cerumen impaction when an
      accumulation of cerumen is associated with symptoms, or prevents needed
      assessment of the ear (the external auditory canal or tympanic membrane), or
      both; 2) clinicians should assess the patient with cerumen impaction by history
      and/or physical examination for factors that modify management, such as one or
      more of the following: nonintact tympanic membrane, ear canal stenosis,
      exostoses, diabetes mellitus, immunocompromised state, or anticoagulant therapy;
      3) the clinician should examine patients with hearing aids for the presence of
      cerumen impaction during a healthcare encounter (examination more frequently than
      every three months, however, is not deemed necessary); 4) clinicians should treat
      the patient with cerumen impaction with an appropriate intervention, which may
      include one or more of the following: cerumenolytic agents, irrigation, or manual
      removal other than irrigation; and 5) clinicians should assess patients at the
      conclusion of in-office treatment of cerumen impaction and document the
      resolution of impaction. If the impaction is not resolved, the clinician should
      prescribe additional treatment. If full or partial symptoms persist despite
      resolution of impaction, alternative diagnoses should be considered. The panel
      offered as an option that 1) clinicians may observe patients with nonimpacted
      cerumen that is asymptomatic and does not prevent the clinician from adequately
      assessing the patient when an evaluation is needed; 2) clinicians may distinguish
      and promptly evaluate the need for intervention in the patient who may not be
      able to express symptoms but presents with cerumen obstructing the ear canal; 3)
      the clinician may treat the patient with cerumen impaction with cerumenolytic
      agents, irrigation, or manual removal other than irrigation; and 4) clinicians
      may educate/counsel patients with cerumen impaction/excessive cerumen regarding
      control measures. DISCLAIMER: This clinical practice guideline is not intended as
      a sole source of guidance in managing cerumen impaction. Rather, it is designed
      to assist clinicians by providing an evidence-based framework for decision-making
      strategies. It is not intended to replace clinical judgment or establish a
      protocol for all individuals with this condition, and may not provide the only
      appropriate approach to diagnosing and managing this problem.

PMID- 18707631
TI  - A clinical overview of pheochromocytomas/paragangliomas and carcinoid tumors.
AB  - Pheochromocytomas/paragangliomas are rare tumors; most are sporadic. Biochemical
      proof of disease is better with measurement of plasma metanephrines and less
      cumbersome than determinations in urine; its implementation is expanding.
      Anatomical imaging with computed tomography or magnetic resonance imaging should
      be followed by functional (nuclear medicine) imaging: chromaffin tumor-specific
      methods are preferred. Treatment is surgical; for nonoperable disease other
      options are available. Overall 5-year survival is 50%. Carcinoid tumors derive
      from serotonin-producing enterochromaffin cells in the fore-, mid- or hindgut.
      Biochemical screening (and follow-up) is done with measurements of 5
      hydroxyindoloacetic acid in urine. For most carcinoids, functional imaging is
      better than other modalities in localizing primary tumors. Surgery is the
      treatment of choice; nonresectable tumors are treated with somatostatin analogs
      or chemotherapy. Overall 5-year survival for patients with carcinoids is 67%.

PMID- 18707637
TI  - Optimizing MIBG therapy of neuroendocrine tumors: preclinical evidence of dose
      maximization and synergy.
AB  - [(131)I]meta-Iodobenzylguanidine ([(131)I]MIBG) has been used for the therapy of
      tumors of neuroectodermal origin since the 1980s. Its role in the management of
      these malignancies remains controversial because of the large variation in
      response rates. Appreciation of the mode of conveyance of [(131)I]MIBG via the
      noradrenaline transporter into malignant cells and of factors that influence the
      activity of the uptake mechanism has indicated various ways in which the
      effectiveness of this type of targeted radiotherapy may be improved. Experimental
      observations indicate that radiolabeling of MIBG to high specific activity
      reduced the amount of cold competitor, thereby increasing tumor dose and
      minimizing pressor effects. We observed supra-additive tumor cell kill and
      inhibition of tumor growth following combined topotecan and [(131)I]MIBG
      treatment. The improved efficacy is related to topotecan's increased disruption
      of DNA repair. Radiation damage to targeted tumors may also be enhanced by the
      use of the alpha-particle emitter [(211)At]astatine rather than (131)I as
      radiolabel. Furthermore, recent experimental findings indicate that [(123)I]MIBG
      may have therapeutic potential over and above its utility as an imaging agent. It
      has recently been demonstrated that potent cytotoxic bystander effects were
      induced by the intracellular concentration of [(131)I]MIBG, [(123)I]MIBG or meta
      [(211)At]astatobenzylguanidine. Identification of the nature of bystander factors
      could be exploited to maximize the specificity and potency of MIBG-targeted
      radiotherapy. By employing a range of strategies, there are good prospects for
      the improvement of the [(131)I]MIBG therapy of neuroectodermal tumors.

PMID- 18707638
TI  - Cell transplantation: back to the bench: introduction.

PMID- 18707639
TI  - Paracrine effects of cell transplantation: modifying ventricular remodeling in
      the failing heart.
AB  - Structural ventricular remodeling determines the clinical progression of heart
      failure and has emerged as an important target for the development of novel
      medical and surgical therapeutic strategies. Cell transplantation is an
      innovative biologic therapy that may restore myocardial structure and function in
      failing hearts. With current forms of cell transplant therapy, true myocardial
      regeneration has been limited. However, cell transplantation can predictably
      limit maladaptive ventricular remodeling through multiple synergistic paracrine
      mechanisms. Some of the paracrine factors released by transplanted cells have
      been defined. These paracrine signals may provide beneficial effects by
      stimulating angiogenesis, limiting matrix disruption, and preventing apoptosis.
      In addition, cell transplantation may induce mobilization and homing of
      endogenous repair cells to injured myocardium through paracrine signals.
      Paracrine mediators released from transplanted cells work through multiple,
      diverse, and interrelated molecular pathways resulting in synergistic effects on
      the remodeling process. Although true myocardial regeneration remains the
      ultimate goal of cell therapy, the anti-remodeling abilities of cell
      transplantation can be harnessed to complement our contemporary surgical
      approaches for patients with myocardial injury at risk of congestive heart
      failure.

PMID- 18707633
TI  - Radiolabeled metaiodobenzylguanidine for the treatment of neuroblastoma.
AB  - INTRODUCTION: Neuroblastoma is the most common pediatric extracranial solid
      cancer. This tumor is characterized by metaiodobenzylguanidine (MIBG) avidity in
      90% of cases, prompting the use of radiolabeled MIBG for targeted radiotherapy in
      these tumors. METHODS: The available English language literature was reviewed for
      original research investigating in vitro, in vivo and clinical applications of
      radiolabeled MIBG for neuroblastoma. RESULTS: MIBG is actively transported into
      neuroblastoma cells by the norepinephrine transporter. Preclinical studies
      demonstrate substantial activity of radiolabeled MIBG in neuroblastoma models,
      with (131)I-MIBG showing enhanced activity in larger tumors compared to (125)I
      MIBG. Clinical studies of (131)I-MIBG in patients with relapsed or refractory
      neuroblastoma have identified myelosuppression as the main dose-limiting
      toxicity, necessitating stem cell reinfusion at higher doses. Most studies report
      a response rate of 30-40% with (131)I-MIBG in this population. More recent
      studies have focused on the use of (131)I-MIBG in combination with chemotherapy
      or myeloablative regimens. CONCLUSIONS: (131)I-MIBG is an active agent for the
      treatment of patients with neuroblastoma. Future studies will need to define the
      optimal role of this targeted radiopharmaceutical in the therapy of this disease.

PMID- 18707640
TI  - Paracrine effects of cell transplantation: strategies to augment the efficacy of
      cell therapies.
AB  - Within the last few years, it has become evident that the beneficial effect of
      cell transplantation on ventricular function and myocardial perfusion is in large
      part mediated through paracrine effects on the host myocardium. Studies in which
      medium conditioned by cultured cells, usually mesenchymal stem cells, were
      injected into infarcted animal hearts have provided definitive evidence of this
      mechanism of action. Paracrine effects of the donor cells include but are not
      limited to angiogenesis, mobilization of both circulating and bone-marrow-derived
      stem cells, activation of cardiac-resident stem cells (CRSCs), and stabilization
      of the extracellular matrix (ECM). These paracrine effects can be augmented by
      transplantation of cells modified to express therapeutically useful transgenes,
      or by preconditioning through hypoxic or pharmacologic means. Strategies to
      enhance the paracrine effects of cell transplantation may thus be employed in the
      next generation of cell therapies, with greater functional benefit.

PMID- 18707641
TI  - Seeing is believing: tracking cells to determine the effects of cell
      transplantation.
AB  - Stem cell therapy holds promise as a therapeutic option for cardiovascular
      disease. As the field of cellular transplantation matures, novel methodologies
      are needed to longitudinally track and evaluate the functional effects of
      transplanted cells. At present, available techniques that hold the greatest
      promise for tracking cell fate include radionuclide labeling, ferromagnetic
      particle labeling, and genetic modification with reporter genes. This review
      describes the benefits and limitations of each technique and provides a summary
      of critical issues regarding stem cell transplantation that have been addressed
      by each imaging modality.

PMID- 18707642
TI  - Improving cell engraftment with tissue engineering.
AB  - Cardiac cell therapy has not yet resulted in long-term clinical benefits or major
      recovery of myocardial function in humans. To date, most of the cardiac effects
      of cell-based therapy are believed to be mediated by a local angiogenic response
      rather than by the formation of neosyncytial contractile units such as had
      initially been hoped for. Therefore, repopulation of the ischemic or infarcted
      heart with progenitor cells that have vasculogenic potential may be an important
      mechanism to improve contractile function, both in the presence of viable and
      nonviable myocardium. This constitutes a focus within scientific reach; however,
      the low engraftment and viability of progenitor cells after transplantation
      necessitate the exploration of novel delivery techniques. Because biomaterials
      have the capacity to improve cell retention, survival, and differentiation,
      tissue engineering is now being explored as an approach to support cell-based
      therapies and enhance their efficacy. In this article, we address current
      progress made in tissue engineering to support cell therapy for the heart, and
      summarize our work in the development of biomaterials toward improving cell
      delivery and vascularization of ischemic tissue.

PMID- 18707643
TI  - MSC immune tolerance in cellular cardiomyoplasty.
AB  - During the past several years, there have been increasing experimental and early
      clinical observations indicating that allogeneic, and even xenogeneic,
      mesenchymal stem cells (MSCs) may be useful for cellular cardiomyoplasty.
      Although the immune tolerance of MSCs is well established in various in vitro
      studies, controversies on the in vivo immune tolerance of MSCs persist.
      Confirmation of the feasibility of allogeneic cellular cardiomyoplasty will have
      vast clinical implications, since it will provide convenient "off-the-shelf"
      donor cells, as a vehicle for gene therapy, and avoid the need to use
      dysfunctional autologous MSCs in senile and/or disabled patients.

PMID- 18707644
TI  - Current status of intramyocardial bone marrow stem cell transplantation.
AB  - Since the first reports of the capacity of bone marrow stem cells for use in
      cardiac repair and regeneration after acute myocardial infarction, today, the
      therapeutic strategy of direct cell administration during cardiac surgery is
      entering clinical practice. Here we report on the current knowledge of the "new
      cellular tool" in the cardiac surgeon's hands that is enabling them to exceed the
      limits of modern methods for myocardial revascularization and repair in cardiac
      surgery. Therefore, we discuss preclinical data focusing on bone marrow stem cell
      types and point to the current mechanistic explanation of their effects. With 7
      years' experience after completing Phase I and Phase II clinical trials with
      cardiac transplantation of autologous intramyocardial bone marrow stem cells, we
      draw conclusions about surgical applicability, safety, and efficacy. At present,
      the functional effects of this treatment are highly promising to become a
      standard treatment. Further clarification by prospective randomized clinical
      Phase III trials is necessary in this field.

PMID- 18707645
TI  - Intraoperative cell transplantation for congestive heart failure: experience in
      China.
AB  - Despite significant improvement in the management of congestive heart failure
      (CHF), it still is a major worldwide public health problem. Currently, cell-based
      regenerative medicine has been developed as a promising therapeutic option for
      patients with CHF. Considering the large and growing population, it is estimated
      that over 5 million patients in China may need such a cell-based therapy to
      replace or repair the damaged myocardium. Cardiac surgery has emerged as an
      important player in heart cell therapy in China in recent years. Here, we
      summarize our achievements in both preclinical and clinical studies of
      intraoperative cell transplantation, and present our understanding of future
      research in this attractive field.

PMID- 18707646
TI  - Current status and future prospects for cell transplantation to prevent
      congestive heart failure.
AB  - Although most cardiac cell therapy trials have focused on patients with acute
      myocardial infarction, attempts at "regenerating" chronically failing hearts have
      also been performed. These studies have entailed use of skeletal myoblasts and
      bone marrow-derived cells. In the case of skeletal myoblasts, the randomized
      placebo-controlled myoblast autologous grafting in ischemic cardiomyopathy
      (MAGIC) trial has failed to show that myoblast injections increased ejection
      fraction beyond that seen in controls but the finding that the highest dose of
      myoblasts resulted in a significant antiremodeling effect compared with the
      placebo group provides an encouraging signal. In the case of bone marrow cells,
      surgical injections of the mononuclear fraction combined with coronary artery
      bypass surgery have not shown a substantial benefit but positive results have
      been reported with intraoperative epicardial injections of CD133(+) progenitors.
      There are three possible reasons for these mixed results. The first is the marked
      heterogeneity of cell functionality (particularly in the case of bone marrow),
      which would expectedly translate into variable clinical outcomes. The second
      reason is the low rate of sustained engraftment. The third possible explanation
      is a mismatch between the choice of end points and the presumed mechanism of
      action of the cells. The initial assumption that adult stem cells could effect
      myocardial tissue regeneration has led to usual focus on ejection fraction as the
      major surrogate endpoint. It is now increasingly recognized that adult stem
      cells, in contrast to their embryonic counterparts, have little if any
      regenerative capacity and that their presumed beneficial effects more likely
      involve paracrine signaling, in which case infarct size, perfusion, or left
      ventricular volumes might be more appropriate markers. Altogether, these
      observations provide a framework for future research, the results of which will
      then have to be integrated in the protocol design of second-generation clinical
      trials.

PMID- 18707648
TI  - The new lung allocation system and its impact on waitlist characteristics and
      post-transplant outcomes.
AB  - Historically, waiting time was the primary determinant of lung organ allocation
      in the United States. Under this system, waiting time grew progressively longer
      as the annual number of transplants reached a plateau, and every year, a
      considerable number of candidates died while waiting. In 2005, the lung
      allocation system changed; under the new system, priority for transplantation is
      determined by medical urgency and expected outcome. The lung allocation score is
      based on survival models that estimate waitlist and post-transplant survival, and
      reflects the net transplant benefit. Early evaluations of the new system indicate
      that waiting time has decreased, the total number of transplants has increased,
      waitlist mortality may be decreasing, and survival after transplantation remains
      unchanged. Over time, refinements in the lung allocation score will likely reduce
      waitlist mortality further and maintain or perhaps improve survival after
      transplantation.

PMID- 18707649
TI  - Current strategies in donor selection and management.
AB  - Lung donor selection and management strategy continues to evolve, driven by the
      scarcity of donor lungs suitable for transplantation and the ever present risk of
      primary graft dysfunction. Selection, based both on data available at referral
      and that added by the retrieval team, was traditionally based on the transplant
      surgeon's clinical experience. Closely analyzed clinical data on factors such as
      age, gas exchange, gram-stain, and even cytokine expression now allow increased
      objectivity of decision making. By contrast, the importance of variables such as
      length of ventilation and even ischemic time remain obscure. Optimal management,
      the key to promoting the marginal lung toward the ideal, is soundly based on the
      rapidly increasing appreciation of the pathophysiology of brain-stem death.
      Algorithms based on this knowledge can be proposed with some confidence, but
      proving their clinical worth is a challenge for the future.

PMID- 18707650
TI  - Adult lung transplantation: technical considerations.
AB  - The technical details of lung transplantation have seen considerable refinement
      with two decades of experience. Recent efforts to expand the donor pool are an
      exciting development. The technical details of donor organ procurement and the
      implantation are discussed here with a note to common pitfalls encountered.

PMID- 18707651
TI  - Pathogenesis, management, and consequences of primary graft dysfunction.
AB  - Primary graft dysfunction continues to be a major contributing factor to
      morbidity and mortality after lung transplantation. This condition is presumed to
      be the result of ischemia-reperfusion injury, which is associated with the
      release of endogenous substances that can activate the innate immune system.
      Primary graft dysfunction has been shown to be an independent risk factor for the
      development of bronchiolitis obliterans syndrome indicating that it can shape
      alloimmune responses. In this review, we focus on the classification,
      pathogenesis, possible prevention strategies, management and consequences of
      primary graft dysfunction.

PMID- 18707652
TI  - Bronchiolitis obliterans syndrome: alloimmune-dependent and -independent injury
      with aberrant tissue remodeling.
AB  - Long-term success in lung transplantation continues to be challenged by chronic
      graft dysfunction, which is manifest as bronchiolitis obliterans syndrome (BOS).
      The mechanisms of BOS involve both immune-mediated pathways (rejection,
      autoimmune-like mechanisms), and alloimmune-independent pathways (infection,
      aspiration, ischemia, primary graft failure), which lead to a fibroproliferative
      responses. BOS correlates histologically with obliterative bronchiolitis in
      terminal bronchioles and evidence of aberrant remodeling in the airway
      epithelium, vasculature, stroma, and lymphoid system. A potentially important
      mechanism that supports the progressive and therapy-resistant nature of BOS is a
      continuous cycle of ongoing injury and aberrant remodeling. Namely, anatomical
      and functional abnormalities induce and exacerbate immune-mediated and alloimmune
      independent pathways through various mechanisms (e.g., epithelial remodeling
      decreases mucociliary clearance that exacerbates aspiration-related injury). From
      this viewpoint, we review current therapeutic strategies and revisit the role of
      transplant surgeons in attenuating the initial transplant-related injuries to
      prevent the lung grafts from entering the remodeling-injury cycle.

PMID- 18707653
TI  - The changing face of head and neck cancer.

PMID- 18707654
TI  - The effect of treatment of radicular dentin on colonization patterns of C.
      albicans.
AB  - OBJECTIVE: The aim of this study was to observe the colonization pattern of C.
      albicans on treated and untreated radicular dentin. STUDY DESIGN: Root sections
      of 10 human mandibular premolar teeth were longitudinally separated into halves.
      The 20 halves were separated into 2 groups and each half served as its own
      control. In Group 1, only gross pulpal remnants were removed with pliers. Root
      canal walls in the corresponding 102 halves (Group 2) were instrumented with
      Gates-Glidden burs and treated with sequential use of 15% EDTA solution for 3
      minutes and 2.5% NaOCl solution for 3 minutes. Finally, all teeth were washed
      with distilled water. Each specimen was placed individually in each well of a 24
      well cell culture plate. After the assembly was sterilized with ethylene-oxide,
      the root canal of each specimen was inoculated with 20 microL of C. albicans (1
      1.5 x 10(6) cfu/mL) that was kept in place for 24 hours for initial attachment.
      Then, 2 mL of SDB was added to each well and the assembly was placed in an
      incubator at 37 degrees C for 10 days. Following the incubation period, the
      specimens were washed, fixed, dehydrated, and processed for scanning electron
      microscopy. RESULTS: C. albicans was present on the root canal surfaces of all
      specimens; however, the colonization pattern was different. In the untreated
      group, the main growth pattern was a dense mass of yeast cells forming biofilm
      layers while hyphal structures were not common. On the other hand, pseudohyphae
      invaded all root canal surfaces in Group 2 and yeast cells were occasionally
      observed. CONCLUSION: The treatment procedures of root canal dentin have a strong
      influence on the colonization pattern of C. albicans. This fact should be
      considered when planning and evaluating in vitro Candida adhesion and/or
      penetration studies.

PMID- 18707655
TI  - Wake up.

PMID- 18707656
TI  - Indications and benefits of continuous peripheral local anesthesia.

PMID- 18707657
TI  - Apprenticeships: preserving the commitment in surgical education.

PMID- 18707658
TI  - Improving surgical residents' performance on written assessments of cultural
      competency.
AB  - CONTEXT: The pressure to implement cultural-competency training at the level of
      GME is high. The rapidly diversifying American population and the ACGME demand
      it, and cultural competency is recognized as a core competency under
      "Professionalism." OBJECTIVES: The objectives for this study were (1) to assess
      residents' baseline levels of cultural competence, (2) define barriers to skill
      acquisition, and (3) examine efficacy of educational programs in improving
      cultural competence. SETTING & PARTICIPANTS: In all, 43 residents from the
      University of Connecticut School of Medicine participated in a prospective,
      Institutional Review Board (IRB)-approved study. DESIGN: During Step 1 (pretest),
      baseline performance was recorded using 3 assessments: (1) Healthcare Cultural
      Competency Test (HCCT), (2) Cultural skills acquisition (CSA), and (3) Clinical
      Scenarios Test (CSE). During Step 2 (Educational Intervention), a 2-part lecture
      that focused on principles of cultural competency and continued self-learning was
      presented. Last, for Step 3 (posttest), the post-program evaluation was
      administered as in Step 1. MAIN OUTCOME MEASURES: Answers for Step 1 (pretest)
      and Step 3 (posttest) were compared using a paired t-test for HCCT and CSE and
      the chi-square test for CSA. RESULTS: Thirty-five replies were evaluated. Every
      resident performed better on the posttest than the pretest. Specifically,
      participants showed 88% improvement in their scores on the HCCT (pretest: 360,
      posttest: 696; p < 0.01), 2-fold improvement on the CSA (pretest: 6, posttest:
      12; p < 0.009), and 40% improvement in CSE (pretest mean score = 23.3, posttest =
      34.6; p < 0.01). Commonly identified barriers to learning included inadequate
      teaching tools and absence of formal training. CONCLUSIONS: Surgery residents
      tested for 3 aspects of cultural competence prior to and after teaching sessions
      showed marked improvement on all 3 assessment measures after this brief
      intervention.

PMID- 18707659
TI  - Objective assessment of training surgical skills using simulated tissue interface
      with real-time feedback.
AB  - OBJECTIVE: We have shown previously that achieving competent performance of basic
      laparoscopic skills is possible in difficult conditions. We hypothesize that real
      time performance feedback adds to the quality of proficiency-based simulator
      training for performance and forces applied to conventional surgical tools while
      tying square knots and running suture throws. DESIGN: A silk suture was preplaced
      on a simulated skin pad to assess incision closure by tying square knots and in
      separate trials to evaluate closure with the task of placing a running suture.
      The order of task performance was assigned randomly, and each task was repeated 5
      times before switching to the second task. In all, 10 repetitions per task were
      performed by each student. After completion of the second surgical task, the
      cycle was repeated to test adaptation and retention of motor-skill capabilities.
      Half the participants were provided with a graphic display in dial format to
      indicate applied force. SETTING: Bench-top setup of apparatus was performed in a
      laboratory at Virginia Commonwealth University, Department of Surgery.
      PARTICIPANTS: Twelve second-year medical students with no surgical skills
      background participated in the study. RESULTS: Results from the knot-tying task
      indicated that the average force exerted on tissue forceps by the left hand in
      the blinded group who performed simple knots actually increased over repeated
      trials, as opposed to what was achieved by the group that had real-time feedback
      of their forces being applied. For the running suture, the task average force
      exerted on surgical tools by both hands was greater in the blind group relative
      to those viewing real-time graphic feedbacks of forces generated over repeated
      trials. CONCLUSION: Inclusion of real-time objective assessment in evaluation of
      surgical skills minimizes subjective evaluation of performance capabilities. A
      direct correlation between real-time feedback regarding force exerted and extent
      of surgical task completion was noted.

PMID- 18707660
TI  - Operating room assist: surgical mentorship and operating room experience for
      preclerkship medical students.
AB  - BACKGROUND: Despite the importance of preclerkship experiences, surgical
      education has essentially remained confined to the third-year operating room
      experience. According to experience-based learning theory, the acquisition of new
      clinical knowledge is a dynamic process of social enculturation and professional
      identity development that requires active participation, clinical applicability,
      and direct interaction with doctors and other members of the medical team. In
      conjunction with a previously described surgical skills elective, we created a
      new clinical elective in which preclerkship medical students were assigned a
      surgical mentor and invited into the operating room to assist in surgeries.
      METHODS: The elective paired 36 first-year students with 24 surgeons and
      instructed students to participate in at least 2 surgeries over the 3-month
      elective period. Students, surgeons, and operating room nurses filled out
      questionnaires after each surgery. RESULTS: Although 6 students failed to enter
      the operating room, 30 students scrubbed and gowned for a total of 62 procedures
      during the elective period. Although most students reported the operating room to
      be a comfortable learning environment in which they were actively included,
      students consistently underrated their performance and contribution to the
      surgical team compared with the surgeons' and nurses' ratings. With 75% of
      students who reported using a previously learned surgical skill during each
      surgery, this elective succeeded in allowing preclerkship medical students the
      opportunity to participate actively in the operating room. CONCLUSIONS: Early
      surgical exposure is critical for attracting student interest in careers in
      surgery. We believe that these early clinical experiences, combined with strong
      mentorship from the surgical faculty, will eventually lead to greater success
      during clerkships and greater interest in surgery as a career.

PMID- 18707661
TI  - Pasteur's Quadrant: preparing training programs for "use-inspired" surgical
      research.
AB  - Ensuring that scientific research is an integral element of surgical residency
      training is critical to the future viability of the field. The ability to nurture
      surgeon-scientists, invoke them to ask pertinent questions, design experiments,
      and translate these findings into clinical applications will set this specialty
      apart from competing fields. Involving residents and younger faculty in this
      process of translational research is crucial to develop academic leaders and
      improve patient care. It is as critical as it is complex. Here, we propose that
      this objective can be attained only if academic departments of surgery recognize
      its value, create a solid framework of support, encourage partnerships, and above
      all provide the patient and essential mentorship that residents and young faculty
      need to pursue meaningful surgical research. To provide usable frameworks, a
      unique 2-dimensional quadrant termed "Pasteur's Quadrant" is generated based on
      the original work of Stokes. Briefly, it creates 4 quadrants that separate pure
      basic science or discovery (X-axis) from applied research or innovation (Y-axis).
      In doing so, it also defines a median-research that satisfies both goals:
      scientific advancement AND clinical improvement. This novel use-inspired method
      of categorizing research provides guidelines to select research programs
      prudently. Using the Pasteur's Quadrant approach to the conduct of resident
      performed surgical research offers several advantages: It is clinically
      applicable; it advances goals of fundamental scientific research; it is
      provocative, productive, and retains high visibility; and it makes it attractive
      to funding agencies and industry alike. Lastly, it charts a vibrant course for
      their main beneficiaries, residents and academic surgical programs.

PMID- 18707662
TI  - Commentary: Academic surgery--a soldier on the front line.

PMID- 18707663
TI  - Resident work-week regulations: historical review and modern perspectives.

PMID- 18707664
TI  - Subungual squamous cell carcinoma of the toe: working toward a standardized
      therapeutic approach.
AB  - Subungual squamous cell carcinoma (SCC) is a rare malignancy with very few
      reported cases that occur on the toe. The etiology of these lesions is not known,
      and although this location is generally considered low risk for metastasis, cases
      of inguinal lymph node metastasis after toe amputation have been reported.
      Patients with subungual disease may meet criteria other than location that
      increase their risk for metastasis. Currently, no standardized approach to
      therapy for these patients has been established. In this article, we describe a
      patient with SCC of the right fourth toe with no clinical evidence of lymph-node
      metastasis. This patient underwent toe amputation and has done well for 2.5 years
      with no evidence of recurrence. We discuss this case of subungual SCC of the toe
      along with others in the literature to propose an optimal standardized approach
      for therapy and follow-up. In so doing, we aim to advance medical knowledge of
      subungual SCC and to improve patient care.

PMID- 18707665
TI  - Delayed presentation and treatment of tracheobronchial injuries due to blunt
      trauma.
AB  - BACKGROUND: Blunt thoracic trauma that results in tracheobronchial injury is
      difficult to diagnose. Many injuries are catastrophic and result in early
      mortality. Others are not immediately life threatening and are missed at initial
      presentation. Some of those injuries will later become symptomatic and will
      require medical attention. Ideal treatment in that situation is not yet clearly
      defined. OBJECTIVES: The objective is to review the current literature of delayed
      diagnoses of traumatic tracheobronchial injuries, their management, and the
      results of the most common repair methods. An interesting case report from this
      institution is presented as well. DESIGN: A Medline search of the English
      literature of delayed presentation of tracheobronchial injuries over the past 10
      years was performed. Delayed diagnosis was defined as injuries not identified
      during the initial hospitalization. RESULTS: The median time from initial
      presentation to diagnosis was 6 months. Dyspnea (56%) and pneumonia (39%) were
      the most common complaints. No difference in complications was observed between
      parenchymal sparing procedures and resections. CONCLUSIONS: Despite delays in
      presentation and the radiographic appearance of destroyed distal lung, proximal
      injuries can often be repaired without sacrifice of distal lung parenchyma.
      Bronchial sleeve resections or end-to-end anastomosis can be performed safely in
      most situations.

PMID- 18707666
TI  - Implementation, construct validity, and benefit of a proficiency-based knot-tying
      and suturing curriculum.
AB  - OBJECTIVES: The aim of this proficiency-based, open knot-tying and suturing study
      was to evaluate the feasibility of implementing this curriculum within a
      residency program, and to assess construct validity and educational benefit.
      METHODS: PGY1 residents (n = 37) were enrolled in an Institutional Review Board
      (IRB)-approved prospective study that was conducted over a 12-week period.
      Trainees viewed a video tutorial during orientation and as needed; they self
      practiced to proficiency for 12 standardized knot-tying, practiced suturing
      tasks; performed 1 repetition of each task at baseline and posttesting; and
      completed questionnaires. RESULTS: Curriculum implementation required 376 person
      hours, and material costs were $776. All trainees achieved proficiency within
      allotted 12 weeks. Overall, trainees completed 141 +/- 80 repetitions over 12.7
      +/- 5.3 hours in addition to performing 13.4 +/- 12.4 operations. Baseline
      trainee and expert performance were significantly different for all 12 tasks and
      composite score (732 +/- 294 vs 1488 +/- 26, p < 0.001), which supported
      construct validity. Baseline trainees demonstrated significant improvement at
      posttesting according to composite scores (732 +/- 294 vs 1503 +/- 131, p <
      0.001), which validates skill acquisition. CONCLUSIONS: Implementation of this
      proficiency-based curriculum within the constraints of a residency program is
      feasible. This curriculum is educationally beneficial and cost effective; our
      data support construct validity. Evaluation of transferability to the operating
      room and more widespread adoption of this curriculum are warranted.

PMID- 18707667
TI  - Under a microscope:Julius H. Jacobson, MD (1927-).

PMID- 18707668
TI  - R for reflection.

PMID- 18707669
TI  - In vitro evaluation of combination antifungal activity against Fusarium species
      isolated from ocular tissues of keratomycosis patients.
AB  - PURPOSE: To determine the minimum inhibitory concentrations (MICs) of five
      antifungal agents against Fusarium species isolated from ocular tissues and to
      evaluate anti-Fusarium species activities of eight combination treatments in
      vitro. DESIGN: Experimental research. METHODS: Thirty-eight isolates of Fusarium
      species were collected from patients' ocular tissues and were cultured in vitro.
      The MICs of natamycin, terbinafine, itraconazole fluconazole, and amphotericin B,
      either used alone or combined with other compounds, were evaluated by
      checkerboard microdilution technique based on the Clinical Laboratory Standards
      Institute proposed standard. The interactions were assessed using the Fractional
      Inhibitory Concentration Index model. RESULTS: In the MIC study, the MIC(90) of
      each drug used alone were: natamycin, 16 microg/ml; terbinafine, 8 microg/ml;
      itraconazole, >16 microg/ml; fluconazole, >64 microg/ml; and amphotericin B, 4
      microg/ml. Synergism was obtained in the amphotericin B plus terbinafine (81.6%)
      group and in the amphotericin B plus itraconazole (84.2%) group, with an
      obviously decreased MIC value of amphotericin B. Antagonism was shown in the
      natamycin plus azoles and in the natamycin plus terbinafine groups in 52.6% to
      60.5% of Fusarium species strains. CONCLUSIONS: Amphotericin B plus terbinafine
      or itraconazole demonstrated more effective anti-Fusarium species activity than
      single-use in vitro treatment, which implies that these combinations may be
      helpful in treating fungal keratitis. The combinations of natamycin plus azoles
      or natamycin plus terbinafine were not satisfactory and can be avoided. Further
      in vivo studies are needed to elucidate the potential usefulness of these
      combination therapies.

PMID- 18707670
TI  - Prospective comparison of microbial culture and polymerase chain reaction in the
      diagnosis of corneal ulcer.
AB  - PURPOSE: To compare polymerase chain reaction (PCR) to microbial culture for the
      detection and identification of bacterial and fungal pathogens in microbial
      keratitis. DESIGN: Prospective cohort study. METHODS: A total of 108 consecutive
      corneal ulcers were cultured and analyzed by PCR using pan-bacterial and pan
      fungal primers. PCR products were cloned, sequenced, and compared to culture
      results using standard bioinformatics tools. RESULTS: Of the 108 samples, 56 were
      culture-positive, 25 for bacteria and 31 for fungi; 52 were culture-negative.
      After eliminating false-positive PCR products, 94 of 108 were positive by PCR, 37
      for bacteria and 57 for fungi. Nineteen of 25 bacterial culture-positive samples
      were positive by PCR, and 29 of 31 samples culture-positive for fungi were
      positive by PCR. The majority of sequenced PCR products matched the positive
      culture results. Of the 52 culture-negative samples, 46 (88%) yielded pathogen
      deoxyribonucleic acid (DNA) PCR products, 18 bacterial and 28 fungal. These
      represented a variety of species, including at least three novel previously
      uncultured microbes. CONCLUSIONS: PCR detects microbial DNA in the majority of
      bacterial and fungal corneal ulcers, and identifies potentially pathogenic
      organisms in a high proportion of culture-negative cases. Yield and concordance
      with culture are higher for fungal than bacterial ulcers. Practical use of the
      technique is limited by artefactual amplification of nonpathogenic organisms. PCR
      may be used as an adjunct to culture to identify potential pathogens in microbial
      keratitis.

PMID- 18707671
TI  - Clinical features of immune rejection after corneoscleral transplantation.
AB  - PURPOSE: To summarize the clinical features of immune rejection after
      corneoscleral transplantation. DESIGN: A retrospective, noncomparative,
      observational case series. METHODS: Patients who received corneoscleral
      transplantation because of whole corneal ulcer or corneal perforation at Shandong
      Eye Institute from July 1, 2003 through July 31, 2005 were included. Fourteen
      patients (14 eyes) with immune rejection but not recurrence or other
      complications were reviewed, including ocular vision, rejection onset time,
      symptoms, and characteristics. RESULTS: The average rejection time in the 14 eyes
      was 35 days. The rejection arose rapidly, and the mean best-corrected visual
      acuity decreased to counting fingers or hand movements. Circular limbal
      congestion and edema developed with circuitous and dilatational vessels. Whole
      graft edema and Descemet membrane folds were present, but no epithelial rejection
      line, endothelial rejection line, or keratic precipitate were observed. The
      average intraocular pressure (IOP) dropped from 13.6 mm Hg to 7.4 mm Hg. Seven
      eyes had shallow anterior chambers (AC). Retinal and choroidal edema was observed
      in five eyes. CONCLUSIONS: The clinical features of immune rejection after
      corneoscleral transplantation include rapid onset of rejection, vision decrease,
      circular limbal congestion and edema with circuitous and dilatational vessels,
      whole graft edema and shallow AC, low IOP, and no rejection line or keratic
      precipitate.

PMID- 18707672
TI  - Thickness profiles of retinal layers by optical coherence tomography image
      segmentation.
AB  - PURPOSE: To report an image segmentation algorithm that was developed to provide
      quantitative thickness measurement of six retinal layers in optical coherence
      tomography (OCT) images. DESIGN: Prospective cross-sectional study. METHODS:
      Imaging was performed with time- and spectral-domain OCT instruments in 15 and 10
      normal healthy subjects, respectively. A dedicated software algorithm was
      developed for boundary detection based on a 2-dimensional edge detection scheme,
      enhancing edges along the retinal depth while suppressing speckle noise.
      Automated boundary detection and quantitative thickness measurements derived by
      the algorithm were compared with measurements obtained from boundaries manually
      marked by three observers. Thickness profiles for six retinal layers were
      generated in normal subjects. RESULTS: The algorithm identified seven boundaries
      and measured thickness of six retinal layers: nerve fiber layer, inner plexiform
      layer and ganglion cell layer, inner nuclear layer, outer plexiform layer, outer
      nuclear layer and photoreceptor inner segments (ONL+PIS), and photoreceptor outer
      segments (POS). The root mean squared error between the manual and automatic
      boundary detection ranged between 4 and 9 mum. The mean absolute values of
      differences between automated and manual thickness measurements were between 3
      and 4 mum, and comparable to interobserver differences. Inner retinal thickness
      profiles demonstrated minimum thickness at the fovea, corresponding to normal
      anatomy. The OPL and ONL+PIS thickness profiles respectively displayed a minimum
      and maximum thickness at the fovea. The POS thickness profile was relatively
      constant along the scan through the fovea. CONCLUSIONS: The application of this
      image segmentation technique is promising for investigating thickness changes of
      retinal layers attributable to disease progression and therapeutic intervention.

PMID- 18707673
TI  - [Papillary fibroelastoma of mitral leaflet revealed by a cerebrovascular
      accident. Case report].
AB  - Papillary fibroelastoma is a benign primitive cardiac tumour, which can be
      associated with serious embolic complications. We report on a 37-year-old woman
      admitted for a cerebrovascular accident. Transthoracic and transesophageal
      echocardiography revealed a small and pedunculated mass attached to the anterior
      mitral leaflet. Because of the severity of its symptoms and its high embolic
      potential, the tumour was surgically excised and histologically diagnosed as a
      papillary fibroelastoma. The postoperative period was uneventful and the patient
      was discharged at the third day. Papillary fibroelastoma must be surgically
      treated because of its high embolic potential and its severe prognosis.

PMID- 18707674
TI  - [Extra-nodal T lymphomas of the nasal cavities and sinuses].
AB  - INTRODUCTION: Extra-nodal T lymphomas of the ear, nose, and throat (ENT) are
      unusual in Western countries, with differential diagnosis from other destructive
      and necrotizing lesions of the sino-nasal tract often difficult. MATERIAL AND
      METHODS: Eleven cases of extra-nodal lymphomas of the upper aerodigestive tract
      tract managed in the ENT department of F. Hached hospital in Sousse, Tunisia,
      were retrieved over a 10-year period (1995-2004). The aim of our study was to
      report the clinical and pathological data and the outcome for each patient.
      RESULTS: The median age of patients was 41-years. The most frequent site of
      involvement was the nasal cavity. Clinically, the symptoms were not specific.
      Histological examination identified two cases of T/NK lymphoma and nine cases of
      T-lymphoma not otherwise specified. Immunohistochemistry and in situ
      hybridization techniques positively detected Epstein-Barr virus in tumoral cells,
      in seven cases. Tumor staging, in 10 patients, found distant metastasis in three.
      Nine patients underwent the following treatment: exclusive radiotherapy (one
      patient), radiochemotherapy (three patients), and exclusive polychemotherapy
      (five patients). The two remaining patients had no treatment because of a rapidly
      unfavorable progression. After a median follow-up of 11-months, clinical outcome
      consisted in death in seven patients and remission in three patients; one patient
      was lost of follow-up. CONCLUSION: Extra-nodal lymphomas of the ORL tract are
      rare in Tunisia. Clinical presentation is not specific, depending on the lymphoma
      location. Diagnosis relies on clinical presentation and immunophenotypic and
      molecular characteristics; morphological features are not specific. These are
      aggressive lymphomas, often requiring multidisciplinary management.

PMID- 18707675
TI  - Homogenous amniotic membrane as a biological dressing for oral mucositis in rats:
      histomorphometric analysis.
AB  - OBJECTIVE: Oral mucositis is a frequent and significant side effect of
      chemotherapy and/or radiation therapy. The purpose of this study was to evaluate
      the effects of the homogenous amniotic membrane (HAM) as a biological dressing
      for oral mucositis induced by 5-fluorouracil (5-FU) in the labial fornix region
      of inferior incisors in rats. METHODS: Sixty rats were divided into three groups:
      control (50% acetic acid), 5-FU (50% acetic acid and 5-fluorouracil-induced oral
      mucositis) and 5-FU+HAM (50% acetic acid and 5-fluorouracil-induced oral
      mucositis, and treated with HAM). Histological analyses were done 3, 7, 14 and 21
      days after applying the acetic acid. RESULTS: HAM showed not only no signs of
      rejection as well as an excellent tissue adherence to the ulcerated surface.
      Histomorphometric analysis indicated a lower quantity of inflammatory cells in
      the 5-FU+HAM group in all periods when compared to the other groups and there was
      a statistically significant difference in the 3- and 7-day periods (P<0.001).
      CONCLUSIONS: The results of this study suggest that HAM was biocompatible with
      great adhesive power to the ulcerated surface, accelerated the healing process
      and exhibited anti-inflammatory activity. Further studies should be done to
      investigate the potential benefits of this material in clinical trials. HAM could
      lead to improved results as a biological dressing in treatment and management of
      oral mucositis in patients submitted to chemotherapy and/or radiation therapy.

PMID- 18707676
TI  - Mood induced cognitive and emotional reactivity, life stress, and the prediction
      of depressive relapse.
AB  - This study examined a group of participants who were fully remitted from a
      previous episode of major depressive disorder, and evaluated the role of
      cognitive and emotional reactivity to a mood challenge, and life stress in the
      prediction of relapse. Fifty-two participants were evaluated during remission,
      and their reactivity (i.e., change in dysfunctional attitudes and emotional
      state) to a depressed mood induction was evaluated. The cohort was followed up 12
      months after the initial assessment. Thirty-five percent of the sample
      experienced a relapse during the follow-up period. Relapse was predicted by
      higher rates of life stress, and lower levels of emotional reactivity
      (specifically less reduction in happiness) to the mood induction during the
      initial assessment. Cognitive reactivity to the mood induction did not predict
      relapse, nor did the interaction between cognitive reactivity and life stress.
      These findings are discussed in terms of recent literature suggesting that
      depression is associated with insensitivity to emotion context, such that
      depressed individuals display blunted emotional responses to affective stimuli,
      including sadness-inducing stimuli. These findings suggest that insensitivity to
      emotional context may also be a characteristic of euthymic individuals at risk of
      relapse.

PMID- 18707677
TI  - The self-concept of traumatized children and adolescents with or without PTSD.
AB  - This study compared the Piers-Harris 2 scores of youth with PTSD (n=30) to the
      scores of traumatized youth without PTSD (n=60) and a non-traumatized comparison
      group (n=39). In the absence of major comorbid disorders, youth with PTSD
      evidenced significantly lower scores than the traumatized PTSD negatives and
      controls on five of six Piers-Harris 2 scales. With the exception of scores on an
      index of perceived parental acceptance of child behavior, trauma exposure in the
      absence of PTSD was not associated with lower Piers-Harris 2 scores.

PMID- 18707678
TI  - Influence of vascular endothelial growth factor variation on human hippocampus
      morphology.
AB  - BACKGROUND: Morphological abnormalities in hippocampus have been implicated in
      neuropsychiatric disorders, including depression, schizophrenia, and dementia.
      Vascular endothelial growth factor (VEGF) has been demonstrated to have
      neurogenic effects in the hippocampus in rats. However, influence of VEGF
      variation on hippocampus morphology in humans has yet to be shown. Here, an
      integrated genetic and neuroimaging approach was used to investigate whether VEGF
      variation influences hippocampus morphology in humans. METHODS: High-resolution
      magnetic resonance imaging and voxel-based morphometry were used to identify the
      influence of genetic variation of VEGFA [rs833068 (SNP-1), rs833070 (SNP-2),
      rs2146323 (SNP-3) and rs3025020 (SNP-4)] on brain morphology in 47 healthy
      individuals. RESULTS: Variation in VEGFA SNP-2 and SNP-3 showed significant
      effects on hippocampus concentration. CONCLUSIONS: The findings suggest that
      effects of VEGF in hippocampus found in rats extend to humans; further
      understanding of effects of VEGFA variation might have important implications in
      identifying individuals more vulnerable to hippocampus pathology as well as those
      neuropsychiatric populations most likely to benefit from VEGF-mediated
      interventions.

PMID- 18707680
TI  - Ovalbumin encapsulation into liposomes results in distinct degrees of oral
      immunization in mice.
AB  - Oral administration of protein antigens, such as ovalbumin, may result in
      induction of either tolerance or immunization. To avoid oral tolerance, there are
      new strategies to protect the antigens from degradation within the
      gastrointestinal tract and to allow them to reach inductive immunological sites.
      One such strategy is the usage of liposomes. Different parameters may influence
      the stability of liposomes in the gastrointestinal tract. Herein, we studied the
      immunological consequences of oral administration of liposome-encapsulated
      ovalbumin in different strains of mice using different liposomes. Our data
      demonstrated that ovalbumin liposomes improved the induction of oral immunization
      and the degree of improvement depended on the liposome type and on the strain of
      mice used. The mechanism responsible for this differential effect of liposomes
      depended on the site of antigen release and absorption. Therefore, some liposomes
      might be suitable as adjuvants for oral immunization, others for oral tolerance
      induction.

PMID- 18707679
TI  - Impact of the brain-derived neurotrophic factor Val66Met polymorphism on levels
      of hippocampal N-acetyl-aspartate assessed by magnetic resonance spectroscopic
      imaging at 3 Tesla.
AB  - BACKGROUND: This study was conducted to corroborate prior evidence of an effect
      of the brain-derived neurotrophic factor (BDNF) valine (val) to methionine (met)
      amino acid substitution at codon 66 (val66met) polymorphism on measures of N
      acetyl-aspartate (NAA) containing compounds in healthy subjects. METHODS: The NAA
      to creatine (Cre) ratio (NAA/Cre), NAA to choline (Cho) ratio (NAA/Cho), and Cho
      to Cre ratio (Cho/Cre) were measured in the left and right hippocampi, left and
      right dorsolateral prefrontal cortices, occipital lobe, anterior cingulate, and
      white matter of the centrum semiovale of 69 carefully screened healthy volunteers
      utilizing proton magnetic resonance spectroscopic imaging (MRSI) at 3 Tesla (T).
      RESULTS: Val/met subjects exhibited significantly reduced levels of left
      hippocampal NAA/Cre and NAA/Cho compared with val/val subjects. This effect was
      independent of age, IQ, number of voxels, hippocampal volume, or gray matter
      content in the voxels of interest. Analysis of other brain regions showed no
      effect of BDNF genotype on NAA measures. CONCLUSIONS: We confirmed the
      association between the met-BDNF variant and reduced levels of hippocampal NAA
      found with a similar technique at 1.5T. The consonance of our results with prior
      findings adds to the evidence that the BDNF val/met genotype affects hippocampal
      biology with implications for a variety of neuropsychiatric disorders.

PMID- 18707681
TI  - Fast path planning in virtual colonoscopy.
AB  - We propose a fast path planning algorithm using multi-resolution path tree
      propagation and farthest visible point. Initial path points are robustly
      generated by propagating the path tree, and all internal voxels locally most
      distant from the colon boundary are connected. The multi-resolution scheme is
      adopted to increase computational efficiency. Control points representing the
      navigational path are successively selected from the initial path points by using
      the farthest visible point. The position of the initial path point in a down
      sampled volume is accurately adjusted in the original volume. Using the farthest
      visible point, the number of control points is adaptively changed according to
      the curvature of the colon shape so that more control points are assigned to
      highly curved regions. Furthermore, a smoothing step is unnecessary since our
      method generates a set of control points to be interpolated with the cubic spline
      interpolation. We applied our method to 10 computed tomography datasets.
      Experimental results showed that the path was generated much faster than using
      conventional methods without sacrificing accuracy, and clinical efficiency. The
      average processing time was approximately 1s when down-sampling by a factor of 2,
      3, or 4. We concluded that our method is useful in diagnosing colon cancer using
      virtual colonoscopy.

PMID- 18707682
TI  - The relationship between cranial base and maxillo-facial morphology in Egyptian
      children.
AB  - The aim of this study was to investigate the relationship between the cranial
      base and maxillo-facial morphology in Egyptian children. Data were obtained from
      95 lateral cephalograms for 61 boys and 34 girls aged from 7.5 to 9.5 years with
      mean age 8.5 years. Eighteen linear and 14 angular measurements were derived from
      40 landmarks and recorded from the standardized radiographs that were traced
      following methods formerly defined and described. A principal component analysis
      of linear and angular measurements showed that anterior and posterior cranial
      base lengths and cranial base angle were closely associated in different ways
      with different aspects of maxillo-facial morphology in both sexes. This was more
      pronounced in boys. A significant positive relationship was found between
      anterior cranial base length and most of the variables describing the maxillo
      facial morphology in both sexes. Posterior cranial base length was significantly
      correlated to the facial depth. The cranial base angle showed a significant
      negative correlation with the antero-posterior position of maxilla and mandible
      (SNA=-0.34, SNB=-0.27 and ANB=-0.24). In conclusion, cranial base configuration
      plays an important role in maxillo-facial morphology.

PMID- 18707683
TI  - Interventional radiology in the treatment of intracranial vascular injuries and
      fistulae.
AB  - Traumatic intracranial vascular injuries are uncommon. However prompt diagnosis
      and management is essential because of the high morbidity and mortality
      associated with these conditions. The imaging evaluation and potential
      endovascular management of traumatic intracranial aneurysms and traumatic
      intracranial fistulae is discussed.

PMID- 18707684
TI  - Vascularised fibula graft inlaid in a massive bone allograft: considerations on
      the bio-mechanical behaviour of the combined graft in segmental bone
      reconstructions after sarcoma resection.
AB  - SUMMARY: Vascularised fibula transfer (VFT) is a trustworthy procedure in the
      reconstruction of skeletal defects secondary to several pathological conditions.
      Over the last 20 years, progress in diagnosis in skeletal oncology and in
      adjuvant therapy has increased the possibility of applying limb-saving procedures
      in the treatment of bone sarcoma. In this context, VFT appeared to be a valuable
      reconstructive tool following the wide segmental resection of the long bones of
      the limbs. The vascularized fibula allows for fast bone fusion. It also
      demonstrates a tendency of progressive hypertrophy and, in those instances in
      which it is associated with an avascular massive bone allograft (MBA), it induces
      a process of osteo-integration which enhances the biomechanical properties of a
      combined graft. In order to assess the progression of the morphologic and
      structural changes of combined bone grafts we reviewed a group of 31 bone sarcoma
      patients who had had tibia reconstruction with a VFT inlaid in a massive
      allograft. Patients had been operated on between 1994 and 2006. Ages ranged from
      4 to 31 years (mean 14 years). Thirty patients had received neo-adjuvant
      chemotherapy. Morphological variations were investigated by means of serial X-ray
      and CT scan examinations. All patients were regularly reviewed over an average
      time of 75 months (range 14-154 months). Computer assisted analysis was repeated
      at every control and performed at the same levels within the reconstruction, so
      that subsequent CT exams could be compared. We measured the sagittal and
      transverse diameters, total and medullary area, cortical thickness and cortical
      density of the VFT. Cortical thickness and cortical density of the massive bone
      allograft were measured as well. Two different remodelling patterns of the
      combined graft could be noted over time, that depended on the load trend on the
      vascularised fibula and that varied according to the persisting integrity of the
      allograft shell.

PMID- 18707686
TI  - "Letter to the editor: Anterior or posterior obliquity of the lag screw in the
      lateral view--does it affect the sliding characteristics on unstable trochanteric
      fractures?" by Srinivas Kambhampati, Injury 2007;38:785-91.

PMID- 18707685
TI  - Effects of early administration of dexamethasone, N-acetylcysteine and aprotinin
      on inflammatory and oxidant-antioxidant status after lung contusion in rats.
AB  - INTRODUCTION: This experimental setting was undertaken to elucidate and confirm
      the role of inflammatory and oxidant-antioxidant mechanisms on blunt injury
      induced moderate pulmonary contusion (PC). We intended to determine the effects
      of dexamethasone (DXM), N-acetylcysteine (NAC) and aprotinin (APR) in terms of
      their ability to diminish the consequences of acute lung injury due to PC.
      METHODS: Rats were allocated to five subgroups. Except for the control, all
      subgroups had a moderate pulmonary contusion. Following 45 min of observation,
      animals in groups I and II received intraperitoneal saline, group III 10 mg/kg
      DXM, group IV 500 mg/kg NAC and group V 30,000 kIU/ml APR. After the procedure, 6
      h after contusion, blood gas analysis, lung tissue nitric oxide (NO) and
      malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT)
      activity, bronchoalveolar lavage (BAL) fluid and histopathological examination
      were performed. RESULTS: All PaO(2) values decreased significantly in contused
      rats as compared with the control group (p<0.05). DXM, NAC and APR resulted in a
      slight increase in PaO(2) values compared with group II (p<0.05). Lung tissue
      levels of MDA and NO were higher in the contusion group than in the control
      (p<0.05). DXM, NAC and APR all decreased the levels of MDA and NO (p<0.05),
      however the decrease in NO was not found to be significant with APR (p>0.05). SOD
      and CAT activities increased significantly after contusion compared to control
      group (p<0.05). There was no significant difference even though SOD levels were
      elevated in groups III, IV and V compared with contused animals (p>0.05).
      Neutrophils in BAL fluid significantly increased in contused animals (p<0.05).
      Only DXM significantly decreased neutrophil population in BAL fluid (p<0.05).
      Scores for alveolar haemorrhage/oedema were higher in all contusion-performed
      rats than those in the control (p<0.05). Compared with the other drugs, only APR
      significantly improved the haemorrhage/oedema scores compared to sham animals
      (p=0.024). CONCLUSIONS: Our findings demonstrate that moderate bilateral PC
      induced by blunt chest trauma leads to an early inflammatory process which is
      clearly associated with activation of the oxidant-antioxidant cascade. On this
      basis, early supportive treatment with DXM, NAC and APR may yield favourable
      results on pulmonary pathophysiological parameters which are adversely affected
      due to PC.

PMID- 18707687
TI  - REMOVED: Statin prevents plaque disruption in apoE-knockout mouse model through
      pleiotropic effect on acute inflammation.
AB  - This article has been removed, consistent with Elsevier Policy on Article
      Withdrawal. Please see http://www.elsevier.com/locate/withdrawalpolicy. The
      Publisher apologizes for any inconvenience this may cause.

PMID- 18707688
TI  - Quantification of the segmental kinematics of spontaneous infant movements.
AB  - This article introduces a method to capture the movements of the upper and the
      lower limb of infants using an electromagnetic tracking system and to reliably
      calculate the segmental kinematics. Analysis of the spontaneous movements of
      infants is important e.g. in the context of the "General Movement Analysis",
      which aims at the early diagnosis of motor dysfunctions. Due to special
      constraints regarding infant anatomy, previous approaches based on optical
      tracking could only gather position data of the infant' segments, whereas with
      this method in addition relative segment angles can be calculated. The
      spontaneous movements of the infant and simple calibration movements of the hand
      and the foot are used to calculate the joint centers and the joint axes of a
      multi-segmental chain model. The quality of the calibration movements is assessed
      at calibration time by calculating the root mean square deviation from the total
      least squares regression plane. The general accuracy of the recording is
      evaluated by the difference between recorded and estimated sensor positions and
      the difference between recorded and estimated sensor orientations. Movements of
      20 infants between term and 3 months post term age were recorded and processed. A
      first application illustrates how abnormal movement patterns are manifested in
      the segmental kinematics. The results show that the presented method is a
      practicable and reliable way to record spontaneous infant movements and to
      calculate the segmental kinematics.

PMID- 18707689
TI  - Cervical helical axis characteristics and its center of rotation during active
      head and upper arm movements-comparisons of whiplash-associated disorders, non
      specific neck pain and asymptomatic individuals.
AB  - The helical axis model can be used to describe translation and rotation of spine
      segments. The aim of this study was to investigate the cervical helical axis and
      its center of rotation during fast head movements (side rotation and
      flexion/extension) and ball catching in patients with non-specific neck pain or
      pain due to whiplash injury as compared with matched controls. The aim was also
      to investigate correlations with neck pain intensity. A finite helical axis model
      with a time-varying window was used. The intersection point of the axis during
      different movement conditions was calculated. A repeated-measures ANOVA model was
      used to investigate the cervical helical axis and its rotation center for
      consecutive levels of 15 degrees during head movement. Irregularities in axis
      movement were derived using a zero-crossing approach. In addition, head, arm and
      upper body range of motion and velocity were observed. A general increase of axis
      irregularity that correlated to pain intensity was observed in the whiplash
      group. The rotation center was superiorly displaced in the non-specific neck pain
      group during side rotation, with the same tendency for the whiplash group. During
      ball catching, an anterior displacement (and a tendency to an inferior
      displacement) of the center of rotation and slower and more restricted upper body
      movements implied a changed movement strategy in neck pain patients, possibly as
      an attempt to stabilize the cervical spine during head movement.

PMID- 18707690
TI  - Epitope mapping of allergen ovalbumin using biofunctionalized magnetic beads
      packed in microfluidic channels The first step towards epitope-based vaccines.
AB  - Specific allergen immunotherapy is frequently associated with adverse reactions.
      Several strategies are being developed to reduce the allergenicity while
      maintaining the therapeutic benefits. Peptide immunotherapy is one such approach.
      Methods for the simple and rapid identification of immunogenic epitopes of
      allergens (i.e. allergenic epitopes) are ongoing and could potentially lead to
      peptide-based vaccines. An epitope extraction technique, based on
      biofunctionalized magnetic microspheres self-organized under a magnetic field in
      a channel of a simple microfluidic device fabricated from polydimethylsiloxane,
      was applied in the isolation and identification of prospective allergenic
      epitopes. Similarly to chromatographic column separations, the easily replaceable
      plug of self-organized beads in the channel benefits especially from an even
      larger surface-to-volume ratio and an enhanced interaction of the surfaces with
      passing samples. Ovalbumin, the major protein of egg white and a typical
      representative of food allergens, was selected as the model molecule. Highly
      resistant ovalbumin was at first efficiently digested by a magnetic proteolytic
      reactor with trypsin treated with l-1-tosylamido-2-phenylethyl chloromethyl
      ketone and the second step, i.e. capture of allergenic epitopes from the mixture
      of peptides, was performed by a magnetic immunoaffinity carrier with orientedly
      immobilized rabbit anti-ovalbumin IgG molecules. Captured peptides were released
      with 0.05% trifluoroacetic acid. The elution fractions were analyzed by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry. The
      peptide fragment of ovalbumin HIATNAVLFFGR (m/z: 1345.75, position: 371-382) was
      identified as a relevant allergenic epitope in this way. Such a microfluidic
      magnetic force-based epitope extraction technique applied in the epitope mapping
      of ovalbumin has the potential to be a significant step towards developing safe
      and cost-effective epitope-based vaccines.

PMID- 18707691
TI  - Foreword: new developments in CE, CIEF and CE for metabolomics.

PMID- 18707692
TI  - The relationships among verbal short-term memory, phonological awareness, and new
      word learning: evidence from typical development and Down syndrome.
AB  - This study examined the correlates of new word learning in a sample of 64
      typically developing children between 5 and 8 years of age and a group of 22
      teenagers and young adults with Down syndrome. Verbal short-term memory and
      phonological awareness skills were assessed to determine whether learning new
      words involved accurately representing phonological information in memory.
      Results showed a relationship between verbal short-term memory measures and
      typically developing individuals' ability to learn the phonological form of novel
      words but not their ability to learn the physical referent of new words.
      Similarly, individuals with Down syndrome showed impaired verbal short-term
      memory and impaired form but not referent learning. Together, these findings
      specify the circumstances in which an accurate phonological representation within
      short-term memory is required for new word learning.

PMID- 18707693
TI  - Switching to duloxetine in selective serotonin reuptake inhibitor non- and
      partial-responders: effects on painful physical symptoms of depression.
AB  - Painful physical symptoms (PPS) are common in patients with depression. Our
      objective was to evaluate the presence of PPS in a sample of SSRI non- or partial
      responders with MDD and examine the effect of a switch to duloxetine on those
      PPS. Outpatients who met criteria for MDD despite having taken an SSRI
      antidepressant for at least 6 weeks, and who had a Hamilton depression rating
      scale total score of at least 15 and a clinical global impression of severity
      score of at least 3, were randomized to switch to duloxetine by either a direct
      switch or a start-taper switch method. PPS were assessed at baseline and at the
      study endpoint using various measures including six visual analog scales (VAS)
      for pain (overall pain, headache, back pain, shoulder pain, interference with
      daily activities, and time in pain while awake), the pain subscale of the symptom
      questionnaire-somatic subscale, and the bodily pain subscale of the short form-36
      item health survey. Clinically significant levels of pain (mean baseline VAS
      scores >30 mm) were seen across all VAS pain measures prior to switching. Switch
      to duloxetine was associated with significant improvements on all pain measures
      regardless of switch method, and there was evidence for an earlier reduction in
      pain in the start-taper switch group. In summary, MDD patients who were non- or
      partial-responders to SSRI treatment were found to have clinically significant
      pain which improved significantly following switch to duloxetine regardless of
      the switch method utilized.

PMID- 18707694
TI  - B- and T-cell responses in multiple sclerosis: novel approaches offer new
      insights.
AB  - In experimental autoimmune encephalomyelitis (EAE), several target antigens of
      encephalitogenic T- and B-cell responses have been identified. However, in human
      multiple sclerosis (MS) the target antigens of pathogenic T and B cells have
      remained conjectural. Here we discuss how recent methodological advances have
      offered new insights into the nature of B- and T-cell receptor repertoires
      expressed in MS tissues, and how novel approaches have helped to identify
      neurofascin as a target of anti-axonal autoantibodies in MS and EAE.

PMID- 18707695
TI  - Evaluation of serum and urinary myeloid related protein-14 as a marker for early
      detection of prostate cancer.
AB  - PURPOSE: Early detection of prostate cancer by prostate specific antigen testing
      is subject to ongoing controversy. Thus, practical tests to improve or replace
      prostate specific antigen would be highly desirable. In diagnostic studies
      promising results were shown for myeloid related protein-14 in serum and urine.
      However, confirmation in longitudinal population based studies is needed.
      MATERIALS AND METHODS: Incident prostate cancer cases (32) and controls (74)
      matched by age were identified during a 2-year followup of a longitudinal study.
      The group of cases was further complemented by a sample of 24 prostate cancer
      cases recruited before initiation of treatment from a clinical study. A
      commercially available test was used to analyze serum and urinary myeloid related
      protein-14 in blinded fashion. RESULTS: In contrast to prostate specific antigen,
      serum and urinary myeloid related protein-14 could not significantly discriminate
      between prostate cancer cases and controls. CONCLUSIONS: In our study neither
      serum nor urinary myeloid related protein-14 proved suitable to distinguish
      prostate cancer cases from controls. Overall myeloid related protein-14 performed
      much worse than prostate specific antigen and it does not seem useful to reduce
      false-positive findings of prostate specific antigen in the controversial range
      of 4 to 10 ng/ml.

PMID- 18707696
TI  - Outcomes following active surveillance of men with localized prostate cancer
      diagnosed in the prostate specific antigen era.
AB  - PURPOSE: We gained insights concerning outcomes associated with men who elect
      active surveillance for the management of localized prostate cancer. MATERIALS
      AND METHODS: This is a retrospective case series analysis of 40 patients
      diagnosed with localized prostate cancer since 1990 who elected active
      surveillance. RESULTS: A total of 31 patients remained on active surveillance for
      a median of 48 months (range 12 to 168). The 5-year probability of remaining on
      active surveillance was 74%. Most patients who abandoned this strategy did so
      within 33 months of diagnosis (range 12 to 84). An increasing prostate specific
      antigen and anxiety were the 2 most common reasons. A delay in treatment did not
      appear to compromise subsequent outcomes. CONCLUSIONS: Men with low grade
      prostate cancer can elect active surveillance and have excellent long-term
      results.

PMID- 18707698
TI  - The role of cystoscopy in the diagnosis of Hunner's ulcer disease.
AB  - PURPOSE: Interstitial cystitis can be classified into Hunner's ulcer and nonulcer
      disease, which are easily distinguished by cystoscopic examination. Although
      therapeutic options may differ between these 2 groups, the diagnosis of
      interstitial cystitis is currently established by many clinicians in the absence
      of cystoscopy. We determined whether clinical parameters alone without
      cystoscopic evaluation could reliably distinguish the patient with Hunner's ulcer
      vs nonHunner's ulcer disease. MATERIALS AND METHODS: Data were collected on 184
      women and 39 men who met National Institute of Diabetes, Digestive and Kidney
      Diseases criteria for interstitial cystitis and who were evaluated at our
      institution between 1990 and 2005. A total of 86 patients with Hunner's ulcer
      were consecutively identified. Of patients with nonHunner's ulcer disease seen
      during that period a cohort of 137 who were consecutively identified were
      selected as a comparison group. Clinical data on each patient were collected. The
      groups were compared by the 2-sample t test, the Mann-Whitney test when
      appropriate and the chi-square test. RESULTS: No significant differences in
      clinical parameters were found between women and men in either group. The female
      to-male ratio was 6:1 and 3:1 in the nonHunner's and Hunner's ulcer groups,
      respectively. The mean age of patients with Hunner's ulcer was significantly
      higher than that of patients with nonHunner's ulcer disease (60 vs 47 years, t
      test p <0.001). No significant differences in symptom duration, history of gross
      hematuria, history of comorbid disease or visual analog pain scores were found
      between the 2 groups. Microscopic hematuria was present in 27 (31%) and 29
      patients (21%) with Hunner's ulcer and nonHunner's ulcer disease, respectively
      (chi-square test p <0.086). CONCLUSIONS: Although there have been recently
      published methods and markers by which to differentiate Hunner's ulcer vs
      nonHunner's ulcer interstitial cystitis, our data demonstrate that standard
      clinical evaluation cannot reliably distinguish these groups. These findings
      suggest that cystoscopy is needed to accurately identify patients with Hunner's
      ulcer.

PMID- 18707699
TI  - Immunomagnetic quantification of circulating tumor cells as a prognostic factor
      of androgen deprivation responsiveness in patients with hormone naive metastatic
      prostate cancer.
AB  - PURPOSE: We determined whether circulating tumor cells predict prostate specific
      antigen failure in patients with metastatic prostate cancer before endocrine
      therapy and compared their prognostic ability with other clinical factors.
      MATERIALS AND METHODS: Circulating tumor cells were enumerated with the
      CellSearchtrade mark system in whole blood. This system was developed using
      epithelial cell adhesion molecule antibody based immunomagnetic capture and
      automated staining methodology. Prostate cancer cell lines (PC3, LNCaP, DU145)
      and mixed blood from healthy men were analyzed using this system. Blood samples
      from 80 patients with metastatic prostate cancer before endocrine therapy were
      analyzed. Circulating tumor cells were then assessed every 3 months after
      endocrine therapy in these patients. RESULTS: Circulating tumor cell assay
      accuracy and reliability were determined using prostate cancer cell line (PC3,
      LNCaP, DU145) spiking experiments, which demonstrated a strong linear correlation
      (r = 0.99) and a constant recovery rate of 69% +/- 3%, 95% +/- 3% and 89% +/- 2%,
      respectively. The number of circulating tumor cells found ranged from 0 to 222
      per 7.5 ml blood (mean 17 +/- 31, median 14). A threshold of 5 or more
      circulating tumor cells per 7.5 ml blood was used to evaluate the ability of
      circulating tumor cells to predict androgen deprivation responsiveness. Of the 80
      patients 44 (55%) had 5 or more circulating tumor cells with a median androgen
      deprivation responsiveness of 17 months compared to more than 32 months for those
      with fewer than 5 circulating tumor cells (p = 0.007). The presence of
      circulating tumor cells, nadir prostate specific antigen values and Gleason score
      were significant parameters predictive of androgen deprivation responsiveness on
      univariate and multivariate analyses. CONCLUSIONS: In this study the presence of
      5 or more circulating tumor cells in 7.5 ml blood was associated with androgen
      deprivation responsiveness in patients with metastatic prostate cancer before
      endocrine therapy.

PMID- 18707704
TI  - External validation of the Mayo Clinic cancer specific survival score in a
      Japanese series of clear cell renal cell carcinoma.
AB  - PURPOSE: We validated the Mayo Clinic SSIGN (stage, size, grade and necrosis)
      score in an independent Japanese sample of patients. MATERIALS AND METHODS:
      Between 1985 and 2006, 406 consecutive Japanese patients underwent nephrectomy
      for clear cell renal cell carcinoma. The prognostic value of pathological
      features for disease specific survival was evaluated using the Cox proportional
      hazards regression model. The predictive ability of the SSIGN score was evaluated
      using the concordance index. RESULTS: Median followup in the 406 patients was 56
      months. Of the patients 100 died of renal cell carcinoma and the 5-year cancer
      specific survival rate was 78.4%. All features comprising the SSIGN score were
      significantly associated with death from renal cell carcinoma on univariate
      analysis. Primary tumor classification, regional lymph node involvement, distant
      metastasis and Fuhrman nuclear grade were significantly associated with death
      from renal cell carcinoma in a multivariate setting. The median SSIGN score in
      the 406 patients was 3 (range 0 to 15). The concordance index of the SSIGN score
      was 0.814. The 5-year cancer specific survival rate in patients with a score of 0
      to 2, 3 or 4, 5 or 6, 7 to 9 and 10 or more was 96.8%, 92.5%, 78.8%, 57.7% and
      18.1%, respectively. The survival rate in the latter 3 groups was higher than
      reported rates in American and European patients. CONCLUSIONS: The Mayo Clinic
      SSIGN score can be applicable to Japanese patients with renal cell carcinoma with
      a high degree of prognostic accuracy. Future studies are needed to determine
      whether Japanese patients with moderate and high SSIGN scores survive longer than
      their American and European counterparts.

PMID- 18707705
TI  - Practice makes perfect.

PMID- 18707706
TI  - Prostate cancers diagnosed at repeat biopsy are smaller and less likely to be
      high grade.
AB  - PURPOSE: We investigated whether prostate cancer diagnosed on initial prostate
      biopsy had worse pathological outcomes compared to that diagnosed on repeat
      prostate biopsy. MATERIALS AND METHODS: We reviewed 905 newly diagnosed prostate
      cancer cases from 2000 to 2007. Patients were stratified by the number of
      previous biopsies, including the initial biopsy in 690, and 1 and 2 or greater
      negative previous biopsies in 142 and 73, respectively. We analyzed Gleason sum,
      number of cores taken, percent of positive cores and bilaterality of prostate
      cancer. Clinically insignificant cancers were defined according to prostate
      specific antigen density 0.4 ng/ml or less, 3 or fewer positive cores, 50% or
      less of maximum cancer in any core and Gleason sum 6 or less. RESULTS: Prostate
      cancer was diagnosed in 57%, 23% and 21% of cases in the initial, and 1 and 2 or
      greater negative previous biopsies groups, respectively. Initial prostate biopsy
      showed a higher number and percent of positive cores, and the maximum percent of
      prostate cancer involved in a core. However, the Gleason pattern distribution
      differed significantly in the 3 groups with the highest percent (14%) of Gleason
      sum 8 or greater in the subset with 2 or greater negative previous biopsies (p
      <0.01). On multivariate analysis accounting for prostate specific antigen,
      digital rectal examination, age and biopsy schema the number of previous biopsies
      was an independent predictor of the number and percent of positive cores, maximum
      prostate cancer involved in a core, and bilaterality (p <0.01). Only prostate
      specific antigen, digital rectal examination and age but not the number of
      previous biopsies independently predicted Gleason sum (p <0.01). CONCLUSIONS:
      Prostate cancer diagnosed on initial prostate biopsy had higher volume. However,
      there were a significant number of high grade prostate cancers detected on the
      third or greater prostate biopsy, underscoring the importance of repeat prostate
      biopsy in the setting of increased or increasing prostate specific antigen
      despite negative previous prostate biopsy.

PMID- 18707707
TI  - It's time to abandon an upper limit of normal for prostate specific antigen:
      assessing the risk of prostate cancer.

PMID- 18707708
TI  - Renal cell carcinoma in young and old patients--is there a difference?
AB  - PURPOSE: Renal cell carcinoma is rare in patients younger than 40 years and
      conflicting data regarding presentation and outcome are present in the
      literature. We reviewed our experience with young patients with renal cell
      carcinoma and compared them to their older counterparts. MATERIALS AND METHODS:
      We identified 1,720 patients 18 to 79 years old who were treated with partial or
      radical nephrectomy for renal cell carcinoma between 1989 and 2005. Patients were
      grouped according to age and outcome analysis was performed. RESULTS: Of the
      1,720 patients with renal cell carcinoma 89 (5%), 672 (39%) and 959 (56%) were
      younger than 40, 40 to 59 and 60 to 79 years old, respectively. There were no
      significant differences in sex, tumor size, TNM stage or multifocality by age
      group. However, patients younger than 40 years were significantly more likely to
      present with symptomatic tumors (p = 0.028). Additionally, there were significant
      differences in histology by age (p <0.001), that is chromophobe histology
      decreased while papillary histology increased with age. Despite similar tumor
      sizes in each age group the percent of patients treated with partial nephrectomy
      decreased with age. Of patients younger than 40 years 49% were treated with
      partial nephrectomy compared with 35% and 30% of those 40 to 59 and 60 to 79
      years old, respectively (p <0.001). At a median followup of 2.6 years (range 0 to
      14.5) we did not observe a significant difference in cancer specific survival
      according to age (p = 0.17). CONCLUSIONS: Younger patients with renal cell
      carcinoma are more likely to have symptomatic tumors with chromophobe histology,
      although the prognosis appears similar across age groups. Older patients are more
      likely to be treated with radical nephrectomy, which requires careful scrutiny
      for current clinical practice.

PMID- 18707710
TI  - Racial variations in the performance of prostate specific antigen and prostate
      specific antigen density in the era of extended prostate biopsy schemes.
AB  - PURPOSE: The incidence of prostate cancer is known to vary as a function of race.
      To date few studies have evaluated the performance of the prostate specific
      antigen test and its indexes in unique racial populations. We examined the
      performance of prostate specific antigen, prostate specific antigen density and
      transition zone density in racial groups undergoing an extended prostate biopsy
      scheme. MATERIALS AND METHODS: A retrospective review was performed of
      prospectively collected data on 1,115 white, 288 black and 161 Asian/Pacific
      Islander men referred for prostate needle biopsy. All participants had not
      undergone previous biopsy. ROC curves stratified by race were ascertained for
      prostate specific antigen, prostate specific antigen density and transition zone
      density for detecting cancer and high grade cancer (Gleason 3 + 4 or greater).
      RESULTS: Across all races prostate specific antigen density outperformed prostate
      specific antigen for detecting any prostate cancer and high grade cancer.
      Prostate specific antigen and prostate specific antigen density performed best
      for diagnosing high grade cancer and diagnosing cancer in men with an abnormal
      digital rectal examination. When comparing differing races, prostate specific
      antigen density performed the best in Asian/Pacific Islander men for high grade
      cancer detection. The performance of transition zone density was inferior to that
      of prostate specific antigen density. CONCLUSIONS: Racial variations exist in the
      performance of prostate specific antigen and prostate specific antigen density.
      In men of Asian/Pacific Islander descent prostate specific antigen and prostate
      specific antigen density perform better than in white men, especially for
      diagnosing clinically significant, high grade prostate cancer. In general
      prostate specific antigen and prostate specific antigen density perform equally
      well in white and black populations.

PMID- 18707711
TI  - Tailoring technique of laparoscopic partial nephrectomy to tumor characteristics.
AB  - PURPOSE: We use a tailored approach to laparoscopic partial nephrectomy based on
      tumor depth of penetration and proximity to the renal sinus. We evaluated
      differences in perioperative outcomes to determine the value of this paradigm.
      MATERIALS AND METHODS: The surgical approach to hilar clamping and tumor bed
      management during laparoscopic partial nephrectomy included no clamp or suture,
      clamp with no suture, and clamp and suture. The end points assessed
      retrospectively were differences in perioperative, pathological and complication
      outcomes among these groups. RESULTS: Our surgical paradigm was used in 174
      patients, including no clamp or suture in 36, clamp with no suture in 25, and
      clamp and suture in 113. Compared to the other patients those with a clamp and
      suture procedure were older with larger and deeper tumors that were closer to the
      renal sinus-collecting system and more likely to be malignant. Operative time was
      shortest in the no clamp or suture group and in the 2 clamp groups warm ischemia
      and operative times were shorter than in the no suture group. Estimated blood
      loss, hospital stay, surgical margins, complications and recurrences did not
      differ among the groups. A creatinine increase of 0.3 mg/dl or greater was seen
      in 33 patients (19%) following surgery, which was attributable to conversion to
      nephrectomy in 4, contralateral nephrectomy or partial nephrectomy in 3 and
      underlying medical renal disease in 1. In the remaining 25 patients no other
      cause was apparent except renal hilar clamping and tumor resection. CONCLUSIONS:
      A tailored approach based on tumor location and proximity to the renal sinus
      collecting system can limit operative and ischemia times, and technically
      simplify the procedure without adversely impacting morbidity, convalescence and
      oncological outcomes.

PMID- 18707712
TI  - The value of preoperative needle core biopsy for diagnosing benign lesions among
      small, incidentally detected renal masses.
AB  - PURPOSE: We determined the safety and accuracy of preoperative needle core biopsy
      for diagnosing benign lesions among small incidental asymptomatic renal masses.
      MATERIALS AND METHODS: Between February 2000 and December 2007 we received a
      total of 235 preoperative core biopsies from 222 less than 5 cm incidental renal
      masses. Biopsy results were correlated with surgical specimen final pathology
      findings or with patient followup if surgery was avoided. RESULTS: Of the 235
      biopsies 184 (78%) were diagnostic, whereas 51 (22%) were nondiagnostic due to
      insufficient material or contents of only normal, inflammatory, fibrotic or
      necrotic tissue, or blood clot. Diagnostic biopsies revealed 138 malignant (75%)
      and 46 benign (25%) lesions. Of these patients 108 (59%) underwent renal surgery,
      which showed a 100% biopsy accuracy rate for distinguishing malignant from benign
      lesions and a 98% rate for determining histological tumor type. Followup with
      radiological imaging was performed for 59 lesions in patients with nondiagnostic
      biopsies or benign masses and for 16 low grade malignant tumors in elderly
      patients. Lesions remained stable in 61 cases, showed minor size changes in 9 and
      resolved in 5. No patient has shown symptoms or required renal surgery to date.
      Significant biopsy related complications were noted in only 2 patients (0.9%).
      CONCLUSIONS: We found that needle core biopsy was a safe and accurate technique
      for distinguishing between malignant and benign tumors in small asymptomatic
      incidentally detected renal masses. Biopsy of small tumors is associated with a
      relatively high rate of technical biopsy failure, although this may be addressed
      by adopting improved biopsy techniques, as discussed.

PMID- 18707713
TI  - Laboratory evaluation of laparoscopic vascular clamps using a load-cell device-
      are all clamps the same?
AB  - PURPOSE: The use of effective vascular clamps is key to successful laparoscopic
      partial nephrectomy. Based on our clinical experience the occlusive capabilities
      of vascular clamps appeared to be quite variable. We compared the occlusive force
      of currently available laparoscopic vascular clamps. MATERIALS AND METHODS: The
      jaw force of 3 laparoscopic vascular clamps (Aesculap(R), Klein Surgical Systems,
      San Antonio, Texas and Karl Storztrade mark) were measured by clamping a 2.2 mm
      compression load cell (Interface Advanced Force Measurement, Scottsdale, Arizona)
      in pound-force. The variables tested were handheld Satinsky, DeBakey and Storz
      clamps vs bulldog clamps, proximal, middle and distal application position, new
      vs used bulldog clamps and new vs used Satinsky handheld clamps. In addition,
      handheld clamps were tested according to the force generated by the notches in
      the locking mechanism. Force retention was also determined for all instruments
      after clamping a 20Fr latex rubber catheter for an hour. Finally, leak pressure
      studies were performed using a harvested porcine artery to determine the
      relationship between jaw force and leak pressure in mm Hg of bulldog and Satinsky
      handheld clamps using a pressure gauge (Cole-Parmer(R)). RESULTS: Handheld
      vascular clamps provided greater force than bulldog clamps. The proximal position
      closest to the hinge provided the greatest force across all instruments. Compared
      to new clamps the 2-year-old Klein Surgical Systems bulldog clamps showed a
      greater than 40% decrease in jaw force at all positions, whereas the 3-year-old
      Aesculap bulldog clamps decreased in jaw force by less than 9% at all positions.
      The 2-year-old Satinsky handheld clamps showed a decrease of 20%, 9% and 0% at
      the distal, middle and proximal jaw positions, respectively. Also, there was a
      positive correlation between force and the number of notches applied in handheld
      clamps. In addition, all instruments maintained jaw force after 1 hour of
      continuous clamping. Finally, leak pressure studies performed with used clamps
      showed that Klein Surgical Systems bulldog, Aesculap bulldog and Satinsky
      handheld clamps leaked at a pressure of 153 to 223, 465 to 795 and 1,500 to 2,600
      mm Hg, respectively. CONCLUSIONS: Vascular clamps have varying occlusive forces
      according to clamp type, manufacturer, jaw and teeth characteristics, jaw
      clamping position and duration of use. However, across all clamps the jaw force
      was greatest at the proximal position. This is most important when applying
      laparoscopic bulldog clamps. In contrast, all handheld vascular clamps generated
      higher force than intracorporeal bulldog clamps. At 1 notch the handheld vascular
      clamps provided supraphysiological occlusion force regardless of position or
      manufacturer.

PMID- 18707715
TI  - Sites of pain from interstitial cystitis/painful bladder syndrome.
AB  - PURPOSE: In interstitial cystitis/painful bladder syndrome multiple pain sites
      are common. We hypothesized that a careful and systematic description of the pain
      of interstitial cystitis/painful bladder syndrome might provide clues to its
      pathogenesis. MATERIALS AND METHODS: Women with 12 months or greater of
      interstitial cystitis/painful bladder syndrome symptoms underwent a medical
      record review and interview. Each completed a questionnaire that included views
      of the female body and described up to 5 interstitial cystitis/painful bladder
      syndrome pains, noting 40 descriptors for each. RESULTS: Two-thirds of the 226
      patients reported multiple pains. Pain could be consolidated at 4 sites,
      including suprapubic, urethral, genital and nongenitourinary. Most descriptors
      were similar and little evidence indicated that 1 pain influenced pain at another
      site. Another 3 patterns were evident, including 1) a suprapubic > urethral >
      genital > nongenitourinary ranking in site distribution and at each site
      proportions that were solitary, the worst and the most frequent pains, and pains
      that responded to bladder events, 2) site specific allodynia, and 3) for urethral
      and genital pains a wider spectrum of sensations, including burning, stinging and
      sharp. Patients with urethral (38%) or genital (27%) pain did not differ from
      those without such pain in 95% of 44 important characteristics. CONCLUSIONS:
      Suprapubic prominence and changes in the voiding cycle are features consistent
      with but do not prove that the bladder is the pain generator in interstitial
      cystitis/painful bladder syndrome and the pain sites described by patients are
      referred from it. The patients with interstitial cystitis/painful bladder
      syndrome who might have been diagnosed with vulvodynia or urethral syndrome did
      not differ from others in important patient variables.

PMID- 18707716
TI  - Mental health diagnoses in patients with interstitial cystitis/painful bladder
      syndrome and chronic prostatitis/chronic pelvic pain syndrome: a case/control
      study.
AB  - PURPOSE: We compared the rate of mental health disorders in male and female
      patients with pelvic pain and control subjects. MATERIALS AND METHODS: Male
      patients with chronic prostatitis/chronic pelvic pain syndrome (174) and female
      patients with interstitial cystitis/painful bladder syndrome (111) were
      identified from a urology tertiary care clinic population. A control group
      consisting of 72 men and 175 women was also recruited. Subjects completed self
      administered questionnaires that included items about demographics, medical
      history, medication use and urological symptoms. The Patient Health Questionnaire
      was used to identify depression and panic disorder. Multiple logistic regression
      was used to determine odds ratios for the presence of a mental health diagnosis.
      RESULTS: Mental health disorders were identified in 13% of the chronic
      prostatitis/chronic pelvic pain syndrome cases and 4% of male controls (OR 2.0, p
      = 0.04), as well as in 23% of interstitial cystitis/painful bladder syndrome
      cases and 3% of female controls (OR 8.2, p <0.0001). Disease status (case vs
      control) (OR 10.4, p = 0.001) and income greater than $50,000 (OR 0.34, p =
      0.008) were the only 2 variables independently predictive of the presence of a
      mental health diagnosis. Age, gender, race/ethnicity and education were not
      predictive. Medications for anxiety, depression or stress were being taken by 18%
      of patients with chronic prostatitis/chronic pelvic pain syndrome, 37% of those
      with interstitial cystitis/painful bladder syndrome, 7% of male controls and 13%
      of female controls. CONCLUSIONS: Depression and panic disorder are significantly
      more common in men and women with pelvic pain conditions than in controls.
      Medication use data suggest that anxiety and depression may be more difficult to
      treat in patients with urological pain syndromes than in controls.

PMID- 18707717
TI  - The minimally invasive treatment of ureteropelvic junction obstruction: a review
      of our experience during the last decade.
AB  - PURPOSE: The minimally invasive treatment of ureteropelvic junction obstruction
      has evolved during the last decade from endoscopic to laparoscopic and robotic.
      We review our 10-year experience with ureteropelvic junction obstruction, and
      report on our experience and followup. MATERIALS AND METHODS: We reviewed all
      patients treated during the last 10 years. There were 294 procedures performed
      with complete records on 273 patients including 128 retrograde endopyelotomies,
      116 laparoscopic pyeloplasties and 29 robotic pyeloplasties. Technique for each
      procedure is reviewed. Statistical analysis was performed on all results.
      Variables evaluated were gender, age (younger than 41 vs 41 years or older), side
      (right or left), presence of crossing vessels, presence of a high insertion,
      primary or secondary procedure and whether prior endopyelotomy or pyeloplasty had
      been performed. RESULTS: Mean followup for endopyelotomy, laparoscopic
      pyeloplasty and robotic pyeloplasty was 20, 20 and 19 months, respectively, with
      success rates of 60.2%, 88.8% and 100%, respectively. On univariable analysis
      only the presence of crossing vessels or a high insertion was significant for
      laparoscopic pyeloplasty. On multivariable analysis age was significant for
      endopyelotomy and the presence of crossing vessels was significant for
      pyeloplasty. On Kaplan-Meier analysis failures were noted to occur after 5 years
      in both groups. CONCLUSIONS: Laparoscopic pyeloplasty and robotic pyeloplasty are
      superior minimally invasive treatments for ureteropelvic junction obstruction.
      However, endopyelotomy can be used for select patients. Because of late failures
      patients who undergo either of these procedures should receive long-term
      followup.

PMID- 18707718
TI  - Can we accurately identify men with low risk prostate cancer?

PMID- 18707719
TI  - Conserved molecular paradigms pattern smooth muscle in urogenital development.

PMID- 18707720
TI  - Prognostic factors in invasive squamous cell carcinoma of the penis: analysis of
      196 patients treated at the Brazilian National Cancer Institute.
AB  - PURPOSE: We evaluated the role of primary tumor histopathological features for
      predicting regional metastasis and the prognosis in patients with penile squamous
      cell carcinoma. MATERIALS AND METHODS: From April 1996 to January 2007, 202
      consecutive patients with penile carcinoma underwent surgical treatment at our
      institution. Of these patients 196 were studied to identify prognostic factors.
      All histological specimens were examined by the same pathologist. We considered
      certain histological parameters, including histological grade, invasion depth,
      lymphovascular embolization, perineural infiltration, infiltration of the corpus
      cavernosum or spongiosum, urethral infiltration and koilocytosis. RESULTS:
      Variables significantly associated with regional metastasis on univariate
      analysis were stage stratification (p = 0.0338), histological grade (p = 0.0112),
      invasion depth (0.0114), lymphovascular embolization (p <0.0001), perineural
      infiltration (p = 0.0092), corpora cavernosa infiltration (p = 0.0005) and
      koilocytosis (p = 0.0013). In the multivariable model lymphovascular embolization
      and absent koilocytosis were independent risk factors for lymphatic metastasis (p
      = 0.001 and 0.009, respectively). We also found a better survival rate in
      patients with koilocytosis and without lymphovascular embolization (p = 0.001 and
      0.005, respectively). CONCLUSIONS: Lymphovascular embolization and absent
      koilocytosis were independent prognostic factors for the risk of lymphatic
      metastasis. Patients with koilocytosis and without lymphovascular embolization
      had better 5-year survival.

PMID- 18707723
TI  - Results of bilateral nerve sparing laparoscopic retroperitoneal lymph node
      dissection for testicular cancer.
AB  - PURPOSE: We evaluated the feasibility and early oncological outcome of a
      laparoscopic nerve sparing bilateral retroperitoneal lymph node dissection. The
      surgical technique is described. MATERIALS AND METHODS: From July 2004 to
      December 2007 a total of 42 patients with nonseminomatous germ cell tumor (21
      with stage I, 2 with stage IIA marker negative and 19 with post-chemotherapy
      stage IIB disease) underwent transperitoneal bilateral laparoscopic
      retroperitoneal lymph node dissection. The sympathetic trunk and postganglionic
      nerves were identified, and lymphatic tissue was dissected between the nerves.
      Patients with clinical stage I and IIA disease that was lymph node positive at
      laparoscopic retroperitoneal lymph node dissection did not receive additional
      chemotherapy. RESULTS: Surgery was successfully completed in all patients and no
      conversion to open surgery was necessary. Mean operative time was 323 minutes. No
      intraoperative complications occurred. Of patients with stage I and marker
      negative stage IIA disease active tumor was found in 5 retroperitoneal lymph node
      dissection specimens, and no patients had recurrence. Of 19 patients with post
      chemotherapy stage IIB disease teratoma was found in the lymphatic tissue in 4
      (21.0%). No retroperitoneal recurrence was observed. Pulmonary metastases
      developed 9 months after surgery in 1 patient with stage I disease and negative
      retroperitoneal histology, and were treated successfully. All patients are
      currently free of disease at a mean followup of 17.2 months. Antegrade
      ejaculation was preserved in 36 patients (85.7%). CONCLUSIONS: Bilateral nerve
      sparing laparoscopic retroperitoneal lymph node dissection is feasible and
      associated with low morbidity if performed by experienced hands. The oncological
      efficacy of this approach is promising and currently under evaluation.

PMID- 18707724
TI  - Predicting prostate cancer risk through incorporation of prostate cancer gene 3.
AB  - PURPOSE: The online Prostate Cancer Prevention Trial risk calculator combines
      prostate specific antigen, digital rectal examination, family and biopsy history,
      age and race to determine the risk of prostate cancer. In this report we
      incorporate the biomarker prostate cancer gene 3 into the Prostate Cancer
      Prevention Trial risk calculator. MATERIALS AND METHODS: Methodology was
      developed to incorporate new markers for prostate cancer into the Prostate Cancer
      Prevention Trial risk calculator based on likelihood ratios calculated from
      separate case control or cohort studies. The methodology was applied to
      incorporate the marker prostate cancer gene 3 into the risk calculator based on a
      cohort of 521 men who underwent prostate biopsy with measurements of urinary
      prostate cancer gene 3, serum prostate specific antigen, digital rectal
      examination and biopsy history. External validation of the updated risk
      calculator was performed on a cohort of 443 European patients, and compared to
      Prostate Cancer Prevention Trial risks, prostate specific antigen and prostate
      cancer gene 3 by area underneath the receiver operating characteristic curve,
      sensitivity and specificity. RESULTS: The AUC of posterior risks (AUC 0.696, 95%
      CI 0.641-0.750) was higher than that of prostate specific antigen (AUC 0.607, 95%
      CI 0.546-0.668, p = 0.001) and Prostate Cancer Prevention Trial risks (AUC 0.653,
      95% CI 0.593-0.714, p <0.05). Although it was higher it was not statistically
      significantly different from that of prostate cancer gene 3 (AUC 0.665, 95% CI
      0.610-0.721, p >0.05). Sensitivities of posterior risks were higher than those of
      prostate cancer gene 3, prostate specific antigen and Prostate Cancer Prevention
      Trial risks. CONCLUSIONS: New markers for prostate cancer can be incorporated
      into the Prostate Cancer Prevention Trial risk calculator by a novel approach.
      Incorporation of prostate cancer gene 3 improved the diagnostic accuracy of the
      Prostate Cancer Prevention Trial risk calculator.

PMID- 18707725
TI  - Prognostic role of histological necrosis for nonmetastatic clear cell renal cell
      carcinoma: correlation with pathological features and molecular markers.
AB  - PURPOSE: We defined the prognostic role of tumor necrosis and its extent in
      nonmetastatic clear cell renal cell carcinoma. Also, we further investigated its
      pathogenesis by correlating this tumor feature with other pathological
      characteristics and molecular markers related to the von Hippel Lindau-hypoxia
      inducible factor pathway and to tumor proliferation. MATERIALS AND METHODS: A
      total of 213 patients with nonmetastatic clear cell renal cell carcinoma were
      evaluated. Mean followup was 66 months. The presence and extent of histological
      necrosis were correlated with clinicopathological factors, Ki-67 antigen
      expression calculated by the MIB-1 (Ki-67 antibody) index, pVHL, HIF-1alpha, the
      tumor infiltrating lymphocyte subset and cancer specific survival. RESULTS:
      Histological necrosis was present in 63.8% of clear cell renal cell carcinoma
      cases. Necrosis was significantly associated with grade and the degree of tumor
      infiltrating lymphocytes, while its extent correlated significantly with grade,
      the degree of tumor infiltrating lymphocytes and stage. Tumor necrosis was a
      significant prognostic factor, which was confirmed even when limiting analysis to
      patients with intracapsular renal cell carcinoma. On multivariate analysis
      histological necrosis was not an independent predictor of cancer specific
      survival. The extent of tumor necrosis was not a significant prognostic factor.
      The presence and extent of histological necrosis was not associated with high Ki
      67 expression and it did not correlate with pVHL expression or with nuclear and
      cytoplasmic HIF-1alpha expression. CONCLUSIONS: Based on our results we cannot
      support histological necrosis and its extent as prognostic factors for clear cell
      renal cell carcinoma. Efforts should be made to develop nomograms that use
      routinely available and objective predictor variables. The precise mechanism that
      causes tumor necrosis remains unknown but the host immune response might
      significantly contribute to its development.

PMID- 18707726
TI  - Daily cranberry juice for the prevention of asymptomatic bacteriuria in
      pregnancy: a randomized, controlled pilot study.
AB  - PURPOSE: We compared the effects of daily cranberry juice cocktail to those of
      placebo during pregnancy on asymptomatic bacteriuria and symptomatic urinary
      tract infections. MATERIALS AND METHODS: A total of 188 women were randomized to
      cranberry or placebo in 3 treatment arms of A-cranberry 3 times daily (58), B
      cranberry at breakfast then placebo at lunch and dinner (67), and C-placebo 3
      times daily (63). After 27.7% (52 of 188) of the subjects were enrolled in the
      study the dosing regimens were changed to twice daily dosing to improve
      compliance. RESULTS: There were 27 urinary tract infections in 18 subjects in
      this cohort, with 6 in 4 group A subjects, 10 in 7 group B subjects and 11 in 7
      group C subjects (p = 0.71). There was a 57% and 41% reduction in the frequency
      of asymptomatic bacteriuria and all urinary tract infections, respectively, in
      the multiple daily dosing group. However, this study was not sufficiently powered
      at the alpha 0.05 level (CI 0.14-1.39 and 0.22-1.60, respectively, incidence rate
      ratios). Of 188 subjects 73 (38.8%) withdrew, most for gastrointestinal upset.
      CONCLUSIONS: These data suggest there may be a protective effect of cranberry
      ingestion against asymptomatic bacteriuria and symptomatic urinary tract
      infections in pregnancy. Further studies are planned to evaluate this effect.

PMID- 18707729
TI  - Inflammatory myofibroblastic tumors of the genitourinary tract--single entity or
      continuum?
AB  - PURPOSE: Inflammatory myofibroblastic tumor of the genitourinary tract is a
      spindled soft tissue lesion that is often mistaken for sarcoma. These tumors have
      been described in numerous sites in the body and have been assigned many names.
      The relationship between inflammatory myofibroblastic tumor and other
      morphologically similar entities has been a long-standing source of controversy.
      We investigated whether inflammatory myofibroblastic tumors in adults and
      children are the same entity, and whether inflammatory myofibroblastic tumor is
      part of a biological spectrum that includes benign and malignant entities at
      opposite ends. MATERIALS AND METHODS: We performed an extensive review of the
      literature. RESULTS: The literature suggests that with evidence of anaplastic
      lymphoma kinase rearrangement and expression, the lesion is neoplastic rather
      than reactive, differentiating it from previously described lesions. CONCLUSIONS:
      Inflammatory myofibroblastic tumor of the genitourinary tract should be
      considered a neoplasm of uncertain malignant potential, and routine surveillance
      and close clinical followup are recommended. Aggressive therapy (radical
      cystectomy, radiation or chemotherapy) is unwarranted given the indolent and
      often benign clinical course for the majority of cases. To understand the
      diagnostic and prognostic implications future emphasis should be placed on the
      link between genetic abnormalities, and clinical course, therapeutic response and
      ultimate outcome.

PMID- 18707731
TI  - What percentage of patients with newly diagnosed carcinoma of the prostate are
      candidates for surveillance? An analysis of the CaPSURE database.
AB  - PURPOSE: Active surveillance is an option for men with clinically localized
      prostate cancer and may be suitable for those with very low risk disease. We
      determined the percentage of men in a large prostate cancer registry who met
      criteria predictive of latent prostate cancer. We also assessed the percentage of
      men meeting these criteria who chose surveillance. MATERIALS AND METHODS: We
      conducted an observational study of 1,886 men diagnosed with clinically localized
      prostate cancer between 1999 and 2004 from the CaPSURE database. Outcomes were
      percent of men meeting Epstein surveillance criteria (prostate specific antigen
      less than 10 ng/ml, clinical T1 or T2a, prostate specific antigen density less
      than 0.15, fewer than 1 of 3 biopsy cores positive, and absence of Gleason
      pattern 4 and 5 on biopsy) and percent selecting surveillance stratified by risk
      group. RESULTS: Of 1,886 men with all 5 criteria documented 16.4% (310 of 1,886)
      met all 5 surveillance criteria and 9.0% (28 of 310) of men in this very low risk
      category actually chose surveillance compared with 4.3% (68 of 1,576) of patients
      in other risk groups (p <0.01). On multivariable analysis of the entire cohort
      older age was the only demographic predictor of surveillance. Being in the very
      low risk group was also a predictor of surveillance. CONCLUSIONS: Of men
      presenting with localized prostate cancer 16% met the criteria for very low risk
      disease. However, only a small subset of eligible men chose active surveillance,
      suggesting that it may be underused in the management of very low risk prostate
      cancer.

PMID- 18707733
TI  - Does prostate growth confound prostate specific antigen velocity? Data from the
      Baltimore longitudinal study of aging.
AB  - PURPOSE: Although prostate specific antigen velocity was proposed to increase the
      specificity of prostate specific antigen-based screening, there are little
      published data on the effect of differential prostate growth on prostate specific
      antigen velocity. If a patient presents with rising prostate specific antigen
      over a year or more, it would be useful to know whether such a change in prostate
      specific antigen could be explained by prostate growth. Thus, we investigated the
      relationship between changes in prostate size and prostate specific antigen
      changes in a large cohort of men without prostate cancer. MATERIALS AND METHODS:
      We identified 242 men without prostate cancer from the Baltimore Longitudinal
      Study of Aging who had 2 or greater serial pelvic magnetic resonance imaging
      studies and contemporaneous prostate specific antigen measurements. In this
      population we used the t test, correlation coefficients, and regression analysis
      to examine the relationship between prostate specific antigen changes and
      prostate volume changes, as assessed by magnetic resonance imaging. RESULTS: The
      mean age was 55 years. During 4.2 years of median followup, the median rate of
      volume change was 0.6 cc per year (range -9.9 to 11.8), and the median prostate
      specific antigen change was 0.03 ng/ml per year. There was no correlation between
      prostate specific antigen changes and prostate growth, as measured in cc per year
      (r = -0.01, p = 0.9) or the percent change per year (r = 0.07, p = 0.3). On
      multivariate analysis, there was no significant relationship between changes in
      prostate volume and prostate specific antigen changes. CONCLUSIONS: Our data
      suggest that volume increases alone do not cause a high prostate specific antigen
      velocity. Despite growth rates as high as 10 cc per year, prostate specific
      antigen velocity was less than 0.1 ng/ml per year in most men without prostate
      cancer. Thus, differential rates of prostatic growth should not confound the use
      of prostate specific antigen velocity for prostate cancer detection and
      prognostication.

PMID- 18707736
TI  - Retroperitoneal laparoscopic partial nephrectomy: surgical experience and
      outcomes.
AB  - PURPOSE: We present outcomes in 110 consecutive patients who underwent
      retroperitoneal laparoscopic partial nephrectomy performed in a 72-month period
      by a single surgeon (MG). MATERIALS AND METHODS: Patients were placed in the
      flank position and the retroperitoneal space was developed using a balloon
      dissector. Hilar control was achieved with bulldog clamps. Tumor depth and extent
      were evaluated using intraoperative sonography. Perioperative data were assessed
      and outcomes were retrospectively analyzed at a mean followup of 23 months.
      RESULTS: Mean patient age was 62 years. Mean operative time was 199.7 minutes and
      mean postoperative stay was 2.6 days. Mean blood loss was 260.0 ml and mean tumor
      size was 2.4 cm. Final pathological evaluation revealed negative positive margins
      in these cases. Of all tumors 63.7% were pathologically confirmed renal cell
      carcinoma. In 57 patients mean preoperative and postoperative creatinine was 1.1
      and 1.3 mg/dl, respectively, at a mean of 20.6 months. In 47 patients with renal
      cell carcinoma who underwent computerized tomography or magnetic resonance
      imaging during the mean 23-month followup there was 1 incidence of local
      recurrence at 1 year. Conversion to open surgery occurred in 2 cases and
      laparoscopic radical nephrectomy was performed in 4. The rate of major
      complications was 4.5%. CONCLUSIONS: Although it is technically challenging, the
      retroperitoneal approach to laparoscopic partial nephrectomy can be performed in
      a safe and timely manner with perioperative outcomes comparable to those reported
      for open and transperitoneal approaches. Furthermore, this approach allows the
      containment of blood and urine outside the peritoneal cavity. Our intermediate
      term results revealed excellent cancer control and preserved renal function.

PMID- 18707737
TI  - An analysis of the effect of statin use on the efficacy of bacillus calmette
      guerin treatment for transitional cell carcinoma of the bladder.
AB  - PURPOSE: Bacillus Calmette-Guerin is an effective immunotherapy for carcinoma in
      situ of the bladder and it reduces recurrence from resected papillary
      transitional cell carcinoma of the bladder. Many patients receiving bacillus
      Calmette-Guerin therapy are concurrently taking statin agents, which have known
      immunomodulatory properties and may alter the performance of bacillus Calmette
      Guerin. Some data have suggested that patients taking a statin while on bacillus
      Calmette-Guerin therapy experience reduced clinical efficacy. MATERIALS AND
      METHODS: We conducted a retrospective review of 952 consecutive patients from
      1978 through 2006. Time to recurrence and progression to surgery were compared
      between those taking and those not taking a statin by Kaplan-Meier methods and
      multivariable Cox regression controlling for stage and grade. RESULTS: There were
      245 (26%) patients taking a statin before bacillus Calmette-Guerin therapy and
      707 not on statin therapy (74%). A total of 796 patients had recurrence overall
      with 214 in the statin group and 582 in the other group. Median time to
      recurrence was similar between those who did and those who did not use a statin.
      On multivariable analysis statin use was not significantly associated with
      recurrence (hazard ratio 1.04; 95% CI 0.81, 1.34; p = 0.7) or progression to
      surgery (hazard ratio 0.77; 95% CI 0.52, 1.13; p = 0.17) after bacillus Calmette
      Guerin therapy. CONCLUSIONS: This retrospective study in a large cohort of
      patients showed no statistically significant association between statin use and
      recurrence or progression to open surgery in patients treated with bacillus
      Calmette-Guerin for transitional cell carcinoma of the bladder. Based on these
      data patients should not be discouraged from taking statins while undergoing
      bacillus Calmette-Guerin treatment.

PMID- 18707738
TI  - Robotic pyeloplasty--the new standard of care?

PMID- 18707739
TI  - Robotic dismembered pyeloplasty: a 6-year, multi-institutional experience.
AB  - PURPOSE: The introduction of the da Vinci Surgical System to perform complex
      reconstructive procedures, such as repair of ureteropelvic junction obstruction,
      has helped to overcome some of the technical challenges associated with
      laparoscopy. We review our large multi-institutional experience with long-term
      followup of robotic dismembered pyeloplasty. MATERIALS AND METHODS: A total of
      140 patients from 3 university medical centers underwent robotic dismembered
      pyeloplasty. An institutional review board approved retrospective chart review
      was performed to collect demographic, preoperative, operative and postoperative
      data. Patients were analyzed as an entire cohort and then divided into various
      subgroups. RESULTS: Of the cases 117 (84.6%) were primary repairs and 23 (16.4%)
      were secondary repairs. There were 13 (9.3%) patients who underwent concomitant
      stone extraction and 5 (3.6%) procedures were performed on patients with solitary
      kidneys. A crossing vessel was found in 77 (55%) patients. Mean operative time
      was 217 minutes (range 80 to 510), estimated blood loss was 59.4 ml (range 10 to
      600), mean length of hospital stay 2.1 days (range 0.75 to 7) and mean followup
      was 29 months (range 3 to 63). Radiographic resolution of obstruction on first
      postoperative diuretic renal scan or excretory urogram was noted in 134 patients
      (95.7%). There was a 7.1% major complication rate and a 2.9% minor complication
      rate. No statistically significant differences were found in any parameters among
      patients from the various cohorts. CONCLUSIONS: To our knowledge this review
      represents the largest multi-institutional experience of robotic dismembered
      pyeloplasty with long-term followup. Robotic pyeloplasty appears to be safe,
      durable and efficacious for primary and secondary ureteropelvic junction
      obstruction with or without concomitant stone extraction, and for patients with a
      solitary kidney.

PMID- 18707741
TI  - How to use a systematic literature review and meta-analysis.
AB  - PURPOSE: This article introduces practicing urologists to the critical appraisal
      of systematic reviews and meta-analyses to guide their evidence-based clinical
      practice. MATERIALS AND METHODS: Using a urological clinical case scenario we
      introduce a 3-step process in evaluating systematic reviews and meta-analyses by
      considering 1) the validity of the review results, 2) what the results are, and
      3) the extent to which the results can and should be applied to patient care.
      RESULTS: A systematic review seeks to synthesize the medical literature about a
      specific clinical question using explicit methods to perform a comprehensive
      literature search, identify and select eligible studies, critically appraise
      their methods, and judiciously summarize the results considering how they vary
      with study characteristics. When this summary involves statistical methods, ie a
      meta-analysis, reviewers can offer a pooled estimate that will have greater
      precision and will apply more broadly than the individual studies. The quality of
      the underlying studies, the consistency of results across studies and the
      precision of the pooled estimate can considerably affect the strength of
      inference from systematic reviews. CONCLUSIONS: Valid systematic reviews of high
      quality studies can increase the confidence with which urologists and patients
      make evidence-based decisions. Thus, urologists need to recognize the inherent
      limitations, understand the results and apply them judiciously to patient care.

PMID- 18707740
TI  - Clitoral sexual arousal: neuronal tracing study from the clitoris through the
      spinal tracts.
AB  - PURPOSE: Although genital tactile stimulation is regarded as a precursor to
      sexual arousal and a recognized initiator of central nervous system arousal,
      specific afferent neural pathways transmit sensory stimuli of arousal, beginning
      at the epithelial level on the clitoris and following the course of arousal
      stimuli through the central nervous system. Limited knowledge exists of the
      pathway from the cutaneous receptors of nerves originating in the epithelial
      tissue of the clitoris and continuing to spinal cord afferents. Such information
      may contribute to an understanding of sexual arousal, particularly in female
      vertebrates. We further defined the neural pathways and mechanisms responsible
      for arousal originating in the epithelium of the clitoris as well as related
      neural pathways to the spinal cord in a murine model. MATERIALS AND METHODS: We
      performed a comprehensive review of the published relevant clinical and
      histological material from human and nonhuman vertebrate studies. In 29 adult
      female C57B1/6 mice the distribution of pelvic nerves and vessels was mapped.
      Gross dissection of 4 female mice was facilitated by resin injection of the
      vascular system in 2. Neuronal tracing was performed in 25 mice that received
      clitoral injection of wheat germ agglutinin-horseradish peroxidase into the
      clitoris and were sacrificed after 72 to 96 hours. The spinal cord and
      periclitoral tissue were removed and fixed. Immunohistochemistry was performed.
      RESULTS: Gross anatomy of the mouse clitoris showed that pudendal and hypogastric
      nerves have a major role in the innervation of the external genitalia. Neuronal
      tracing revealed that the greatest nerve density was noted in the L5/6 spinal
      cord. The distribution extended from S1 to L2 with no labeling seen in the L3
      spinal cord. Wheat germ agglutinin-horseradish peroxidase labeling was seen
      caudal in levels S1 through L4 and rostral in L2. CONCLUSIONS: Understanding the
      neuroanatomy of the clitoris using a murine model may provide a valuable tool for
      the study of sexual arousal disorders and the further understanding of sexual
      function related to neural pathologies and trauma.

PMID- 18707742
TI  - Evaluating children with nonneurogenic voiding disorders--can we do better?

PMID- 18707743
TI  - Pseudohypericin is necessary for the light-activated inhibition of prostaglandin
      E2 pathways by a 4 component system mimicking an Hypericum perforatum fraction.
AB  - Hypericum perforatum (Hp) has been used medicinally to treat a variety of
      conditions including mild-to-moderate depression. Recently, several anti
      inflammatory activities of Hp have been reported. An ethanol extract of Hp was
      fractionated with the guidance of an anti-inflammatory bioassay
      (lipopolysaccharide (LPS)-induced prostaglandin E2 production (PGE2)), and four
      constituents were identified. When combined together at concentrations detected
      in the Hp fraction to make a 4 component system, these constituents (0.1microM
      chlorogenic acid (compound 1), 0.08microM amentoflavone (compound 2), 0.07microM
      quercetin (compound 3), and 0.03microM pseudohypericin (compound 4)) explained
      the majority of the activity of the fraction when activated by light, but only
      partially explained the activity of this Hp fraction in dark conditions. One of
      the constituents, light-activated pseudohypericin, was necessary, but not
      sufficient to explain the reduction in LPS-induced PGE2 of the 4 component
      system. The Hp fraction and the 4 component system inhibited lipoxygenase and
      cytosolic phospholipase A2, two enzymes in the PGE2-mediated inflammatory
      response. The 4 component system inhibited the production of the pro-inflammatory
      cytokine tumor necrosis factor-alpha (TNF-alpha), and the Hp fraction inhibited
      the anti-inflammatory cytokine interleukin-10 (IL-10). Thus, the Hp fraction and
      selected constituents from this fraction showed evidence of blocking pro
      inflammatory mediators but not enhancing inflammation-suppressing mediators.

PMID- 18707744
TI  - Physical inactivity in Canada: results from the Canadian Community Health Survey
      Cycle 2.2 (2004-2005).

PMID- 18707745
TI  - Immunohistochemical identification and localization of orexin A and orexin type 2
      receptor in the horse gastrointestinal tract.
AB  - The aim of the present study was to investigate the presence and the distribution
      of cells containing orexin A and orexin type 2 receptor in the horse stomach and
      gut, by means of immunohistochemical techniques. Orexin A was identified in the
      stomach fundic and pyloric regions and in the duodenum. In the same stomach
      regions, a large subset of orexin A-positive cells also showed orexin type 2
      receptor-like immunoreactivity. Moreover, in the duodenum, many of them, seemed
      to store serotonin. Characteristically, enteric neurons or ganglia also displayed
      orexin A and, sometimes, orexin type 2 receptor immunoreaction. Orexin A and
      orexin type 2 receptor immunoreactivity was also found in the nerve fibers in the
      enteric submucosal layer. Our results, together with data present in the
      literature, could contribute to the understanding of complex mechanisms
      regulating the horse gut functionality that are depending very likely on the
      consequence of the co-operation of both a central and a peripheral control.

PMID- 18707746
TI  - [Intraorbital cavernous hemangioma].
AB  - Cavernous hemangioma is the most frequent primary vascular orbital tumor in
      adults. This slowly evolving lesion is usually located behind the ocular globe,
      between the extrinsic muscles. It leads to axial exophthalmia. Surgical treatment
      is indicated when there is a risk of visual impairment. The prognosis is related
      to the size of the lesion and its extension. CT scan is rather unspecific, but
      MRI is highly sensitive and specific in case of progressive painless
      exophthalmia.

PMID- 18707747
TI  - Malaria and HIV co-infection in pregnancy in sub-Saharan Africa: impact of
      treatment using antimalarial and antiretroviral agents.
AB  - Malaria and HIV infection represent severe public health problems in sub-Saharan
      Africa, and pregnant women are at increased risk because the two diseases
      intersect in pregnancy, causing adverse perinatal outcome. As access to
      antiretroviral drugs is increasing in the sub-region, and new combinations of
      antimalarial drugs are being implemented while more are being evaluated, there is
      potential for interactions between these therapies. In this report, the impact of
      treatment using antimalarial and antiretroviral agents in pregnant women with
      malaria and HIV co-infection was reviewed, using scientific publications
      identified through a Medline Entrez-Pubmed search with reference to sub-Saharan
      Africa. The safety and operational feasibility of use of antimalarial and
      antiretroviral agents to treat co-infected pregnant women were evaluated.
      Although use of these therapies was shown to improve the health of pregnant women
      with co-infection, low adherence, poor-quality drugs, resource scarcity, lack of
      infrastructure and inadequate treatment in sub-Saharan Africa continue to hamper
      treatment outcome. The absence of studies on interaction between antimalarials
      and antiretrovirals, as well as mounting evidence of treatment failure due to
      drug resistance and adverse drug reactions, in most parts of sub-Saharan Africa,
      make the establishment of new guidelines for the prevention of malaria and HIV
      infection during pregnancy imperative.

PMID- 18707748
TI  - Hantaan virus induces toll-like receptor 4 expression, leading to enhanced
      production of beta interferon, interleukin-6 and tumor necrosis factor-alpha.
AB  - Hantaan virus (HTNV) infects endothelial cells and is associated with increased
      vascular permeability during hemorrhagic fever with renal syndrome (HFRS). The
      pattern of increased vascular permeability is mediated by immune response.
      Therefore, it is necessary to characterize the mechanism of HTNV involvement in
      the host's innate immune. In this study, the expression of five toll-like
      receptors (TLRs) was analyzed in Endothelial vein cells (EVC-304) following HTNV
      infection in vitro. TLR4 showed an altered expression after HTNV infection. HTNV
      infection significantly increased IFN-beta, IL-6 and TNF-alpha secretion from EVC
      304 cells, particularly after lipopolysaccharide stimulation. The increased IFN
      beta, IL-6 and TNF-alpha production was mediated by TLR4 induction, since the
      introduction of the small interfering RNA against TLR4 specifically inhibited the
      HTNV-induced cytokine production. In conclusion, HTNV infection directly induces
      TLR4 expression and thereby enhanced production of IFN-beta, IL-6 and TNF-alpha,
      which may contribute to the host's innate immune response.

PMID- 18707749
TI  - Total nitrogen removal in a hybrid, membrane-aerated activated sludge process.
AB  - The hybrid (suspended and attached growth) membrane biofilm process (HMBP) is a
      novel method to achieve total nitrogen removal from wastewater. Air-filled hollow
      fiber membranes are incorporated into an activated sludge tank, and a nitrifying
      biofilm develops on the membranes, producing nitrite and nitrate. By suppressing
      bulk aeration, the bulk liquid becomes anoxic, and the nitrate/nitrite can be
      reduced with influent BOD. The key feature that distinguishes the HMBP from other
      membrane-aerated processes is that it is hybrid; heterotrophic bacteria are kept
      mainly in suspension by maintaining low bulk liquid BOD concentrations. We
      investigated the HMBP's performance under a variety of BOD and ammonium loadings,
      and determined the dominant mechanisms of nitrogen removal. Suspended solids
      increased with the BOD loadings, maintaining low bulk liquid BOD concentrations.
      As a result, nitrification rates were insensitive to the BOD loadings, remaining
      at 1gNm(-2)day(-1) for BOD loadings ranging from 4 to 17gBODm(-2)day(-1).
      Nitrification rates decreased during short-term spikes in bulk liquid BOD
      concentrations. Shortcut nitrogen removal was confirmed using microsensor
      measurements, showing that nitrite was the dominant form of oxidized nitrogen
      produced by the biofilm. Fluorescence in situ hybridization (FISH) showed that
      ammonia oxidizing bacteria (AOB) were dominant throughout the biofilm, while
      nitrite oxidizing bacteria (NOB) were only present in the deeper regions of the
      biofilm, where the oxygen concentration was above 2mg/L. Denitrification occurred
      mainly in the suspended phase, instead of in the biofilm, decreasing the
      potential for biofouling. When influent BOD concentrations were sufficiently
      high, full denitrification occurred, with total nitrogen (TN) removal approaching
      100%. These results suggest that the process is well-suited for achieving
      concurrent BOD and TN removal in activated sludge.

PMID- 18707750
TI  - Effect of biological wastewater treatment on the molecular weight distribution of
      soluble organic compounds and on the reduction of BOD, COD and P in pulp and
      paper mill effluent.
AB  - Pulp and paper mill wastewater was characterizated, before (influent) and after
      (effluent) biological wastewater treatment based on an activated sludge process,
      by microfiltration (8, 3, 0.45 and 0.22microm) and ultrafiltration (100, 50, 30
      and 3kDa) of the wastewater samples into different size fractions. Various
      parameters were measured on each fraction: molecular weight distribution (MWD)
      using high performance size exclusion chromatography (HPSEC), total organic
      carbon (TOC), biochemical oxygen demand (BOD), chemical oxygen demand (COD),
      total phosphorus (Tot-P), phosphate phosphorus (PO(4)-P), electrical
      conductivity, pH, turbidity, charge quantity and zeta potential. The MWD, TOC and
      COD(Cr) results indicated that the majority of the material present in both the
      influent and effluent was in the medium molecular weight (MW) range (i.e.
      MW<10kDa) with three main MW sub-fractions. There were no significant differences
      in the range of the MWD between the influent and effluent samples. The magnitude
      of the MWD in the effluent was about one half that in the influent, the greatest
      reduction being in the 6kDa fraction. The 3kDa fractions of both the influent and
      effluent showed a considerable increase in BOD(7), probably due to the removal of
      compounds harmful to bacteria in 3kDa ultrafiltration. Influent turbidity
      decreased considerably in microfiltration (8-0.22microm). As the turbidity was
      removed by 0.22microm filtration, the anionic charge quantity started to
      decrease. Particles in the influent and effluent contained 19-29% and 14-20% of
      the total phosphorus, respectively. The major phosphorus fraction was in the form
      of soluble phosphate.

PMID- 18707752
TI  - Delayed initiation of breast development in girls with higher prenatal dioxin
      exposure; a longitudinal cohort study.
AB  - OBJECTIVES: While many studies have assessed the health impacts of PCDD/Fs and
      PCBs on animals and humans, long-term consequences for especially adolescents,
      have not (yet) been well documented. This is certainly also true for the effects
      of PBDE exposure. As part of a longitudinal cohort study, now well into its
      second decade, effects of perinatal and current PCDD/F exposure, as well as
      current dl-PCB and PBDE exposures, on puberty, were assessed. STUDY DESIGN:
      Prenatal, lactational and current PCDD/F, dl-PCB and PBDE concentrations were
      determined using GC-MS. Pubertal development and growth were assessed by means of
      physical examination and the Tanner scale. 33 Children (born between 1986 and
      1991) consented to the current follow-up study. Outcomes were evaluated using
      linear regression or the non parametric Spearman's correlation coefficient.
      RESULTS: A delay in initiation of breast development was found in girls (n = 18)
      with higher prenatal (p = 0.023) and lactational PCDD/F exposure (p = 0.048). The
      males revealed a negative trend with age at first ejaculation. For other
      endpoints on puberty and growth (pubic hair, axillary hair, genital stage,
      length, BMI, testicular volume, menarche) no significant relation was found with
      any of the measured compounds. DISCUSSION AND CONCLUSION: A relation between
      prenatal PCDD/F exposure and later initiation of breast development was seen. A
      Belgian study found a delay in breast development with higher current serum
      concentrations of dioxin-like compounds. The initiation of puberty is a complex
      process and it is yet not clear how dioxin-like compounds precisely affect this
      process prenatally. Further follow-up into adulthood is warranted, in order to
      detect the possibility of developing malignancies and fertility problems.

PMID- 18707751
TI  - Characterization of two adenosine analogs as fluorescence probes in RNA.
AB  - The fluorescence properties of two adenosine analogs, 2-(3-phenylpropyl)adenosine
      [A-3CPh] and 2-(4-phenylbutyl)adenosine [A-4CPh], are reported. As monomers, the
      quantum yields and the mean lifetimes are 0.011 and 6.22 ns for A-3CPh and 0.007
      and 7.13 ns for A-4CPh, respectively. Surprisingly, the quantum yields of the two
      probes are enhanced 11- to 82-fold upon incorporation into RNA, while the mean
      lifetimes decrease 23-40%. The data suggest that a subpopulation of molecules is
      responsible for the fluorescence characteristics and that the distribution of
      emitting and non-emitting structures is altered upon incorporation of the probes
      into RNA. Thus, although both adenosine analogs have low quantum yields as
      monomers, their fluorescence signals are significantly enhanced in RNA.
      Thermodenaturation experiments and CD spectroscopy indicate that incorporation of
      the adenosine analogs into three different RNAs does not alter their global
      structure or stability. Therefore, these probes should be useful for probing
      events occurring close to the site of modification.

PMID- 18707753
TI  - Do high levels of diffuse and chronic metal pollution in sediments of Rhine and
      Meuse floodplains affect structure and functioning of terrestrial ecosystems?
AB  - This paper (re)considers the question if chronic and diffuse heavy metal
      pollution (cadmium, copper, lead and zinc) affects the structure and functioning
      of terrestrial ecosystems of Biesbosch National Park, the floodplain area of
      rivers Meuse and Rhine. To reach this aim, we integrated the results of three
      projects on: 1. the origin, transfer and effects of heavy metals in a soil-plant
      snail food chain; 2. the impact of bioavailability on effects of heavy metals on
      the structure and functioning of detritivorous communities; 3. the risk
      assessment of heavy metals for an herbivorous and a carnivorous small mammal food
      chain. Metal pollution levels of the Biesbosch floodplain soils are high. The
      bioavailability of metals in the soils is low, causing low metal levels in plant
      leaves. Despite this, metal concentrations in soil dwelling detritivores and in
      land snails at polluted locations are elevated in comparison to animals from 'non
      polluted' reference sites. However, no adverse effects on ecosystem structure
      (species richness, density, biomass) and functioning (litter decomposition, leaf
      consumption, reproduction) have been found. Sediment metal pollution may pose a
      risk to the carnivorous small mammal food chain, in which earthworms with
      elevated metal concentrations are eaten by the common shrew. Additional
      measurements near an active metal smelter, however, show reduced leaf consumption
      rates and reduced reproduction by terrestrial snails, reflecting elevated metal
      bioavailability at this site. Since future management may also comprise
      reintroduction of tidal action in the Biesbosch area, changes in metal
      bioavailability, and as a consequence future ecosystem effects, cannot be
      excluded.

PMID- 18707754
TI  - Critical review of mercury fates and contamination in the Arctic tundra
      ecosystem.
AB  - Mercury (Hg) contamination in tundra region has raised substantial concerns,
      especially since the first report of atmospheric mercury depletion events (AMDEs)
      in the Polar Regions. During the past decade, steady progress has been made in
      the research of Hg cycling in the Polar Regions. This has generated a unique
      opportunity to survey the whole Arctic in respect to Hg issue and to find out new
      discoveries. However, there are still considerable knowledge gaps and debates on
      the fate of Hg in the Arctic and Antarctica, especially regarding the importance
      and significance of AMDEs vs. net Hg loadings and other processes that burden Hg
      in the Arctic. Some studies argued that climate warming since the last century
      has exerted profound effects on the limnology of High Arctic lakes, including
      substantial increases in autochthonous primary productivity which increased in
      sedimentary Hg, whereas some others pointed out the importance of the formation
      and postdeposition crystallographic history of the snow and ice crystals in
      determining the fate and concentration of mercury in the cryosphere in addition
      to AMDEs. Is mercury re-emitted back to the atmosphere after AMDEs? Is Hg
      methylation effective in the Arctic tundra? Where the sources of MeHg are? What
      is its fate? Is this stimulated by human made? This paper presents a critical
      review about the fate of Hg in the Arctic tundra, such as pathways and process of
      Hg delivery into the Arctic ecosystem; Hg concentrations in freshwater and marine
      ecosystems; Hg concentrations in terrestrial biota; trophic transfer of Hg and
      bioaccumulation of Hg through food chain. This critical review of mercury fates
      and contamination in the Arctic tundra ecosystem is assessing the impacts and
      potential risks of Hg contamination on the health of Arctic people and the global
      northern environment by highlighting and "perspectiving" the various mercury
      processes and concentrations found in the Arctic tundra.

PMID- 18707755
TI  - Acute effects of hyperglycaemia on plasma concentration of soluble P-selectin and
      von Willebrand factor in healthy volunteers -a prospective randomised double
      blind controlled study.
AB  - This study set out to clarify if isolated hyperglycaemia may directly induce
      acute endothelial and/or platelet activation as diabetes mellitus is a major risk
      factor for cardio- and cerebrovascular diseases with thromboembolic
      complications. 12 healthy volunteers were investigated in a prospective
      randomised, double blind, three-way cross-over trial with a wash-out period of 21
      days. Normoglycemic (4.72 mmol/L), moderate (11.1 mmol/L) or high grade (16.7
      mmol/L) glucose clamps were maintained for 6 hours by infusion of glucose,
      insulin and somatostatin. Volunteers were observed for 24 hours. An increase in
      soluble (s)P-selectin and von Willebrand Factor (VWF) concentrations, of 26+/-15%
      and 21+/-7%, respectively was observed 24 hours after euglycaemic treatment, of
      20+/-7% and 19+/-5%, respectively after moderate hyperglycaemia and of 22+/-13%
      and 18+/-7%, respectively after high grade hyperglycaemia at 24 hours (p<0.6 and
      p<0.004 in all periods and p=0.2-0.9 between periods). In conclusion, acute
      hyperglycaemia for 6 hours does not increase the platelet and endothelial
      activation markers sP-selectin and VWF in healthy volunteers.

PMID- 18707756
TI  - The impact of surgery on survival of elderly women with endometrial cancer in the
      SEER program from 1992-2002.
AB  - OBJECTIVES: Few population-based studies have evaluated surgical treatment and
      outcomes in elderly patients with endometrial cancer. The National Cancer
      Institute's SEER, Surveillance, Epidemiology and End Results, Program provides a
      database to examine this issue. The objective of this study was to determine the
      extent to which elderly women with endometrial cancer receive surgical treatment
      and to evaluate the impact of surgery on survival. METHODS: Data were obtained
      from the SEER registries for expanded races from 1992-2002. The inclusion
      criteria were women ages 50 to 95 with pathologically confirmed endometrial
      cancer. Cases with multiple primaries were excluded. The data were examined with
      respect to histology, radiotherapy use, extent of surgery and FIGO stage. The
      survival data were analyzed using a Cox proportional hazard model. Chi-squared
      tests were used to examine the extent to which elderly women with endometrial
      cancer receive surgical treatment, hysterectomy at minimum. Endometrial cancer
      specific mortality was analyzed. RESULTS: 27,517 women were analyzed with 94% of
      the cohort receiving surgical treatments. There is a significant trend that
      suggests elderly women, aged 65+ years at time of endometrial cancer diagnosis,
      received surgical treatment less often than younger women (p<0.001). The age
      adjusted hazard of death was reduced with surgical intervention. After adjustment
      for stage at diagnosis, histology, and radiotherapy, the hazard ratios for
      endometrial cancer-specific mortality were decreased when surgery was undertaken.
      CONCLUSIONS: In this population-based study, the poor prognosis associated with
      advanced age may be in part associated with the decreased frequency of surgical
      treatment. The reasons need to be further investigated. Continued efforts should
      be directed at providing surgical treatment for elderly patients with endometrial
      cancer.

PMID- 18707757
TI  - Evaluation of protective effect of bee pollen against propoxur toxicity in rat.
AB  - In this study, 28 Wistar female rats (200-250g) were used and divided into four
      equal groups. Group 1 was allocated as the control group. Groups 2-4 were
      administered 100mg/kg/bw/day bee pollen, 20mg/kg/bw/day propoxur, and
      100mg/kg/bw/day bee pollen plus 20mg/kg/bw/day propoxur by gavage for 14 days,
      respectively. At the end of the 14th day, blood and tissues (the liver, kidney,
      brain, and heart) were collected from all animals. Oxidative stress markers (MDA,
      CAT, SOD, GSH-Px) and some other biochemical parameters (total protein, albumin,
      glucose, cholesterol, triglyceride, BUN, creatinine, uric acid, magnesium,
      sodium, potassium, chloride, total bilirubin, GGT, LDH, AST, ALT, and ALP) were
      analyzed. According to the data obtained, propoxur was determined to lead to
      negative changes in most of the biochemical parameters investigated and the
      administration of bee pollen was determined to alleviate these effects.

PMID- 18707758
TI  - Clinical validation of an automated vessel-segmentation software of the
      extracranial-carotid arteries based on 3D-MRA: a prospective study.
AB  - OBJECTIVES: To determine the accuracy of automated vessel-segmentation software
      for vessel-diameter measurements based on three-dimensional contrast-enhanced
      magnetic resonance angiography (3D-MRA). METHOD: In 10 patients with high-grade
      carotid stenosis, automated measurements of both carotid arteries were obtained
      with 3D-MRA by two independent investigators and compared with manual
      measurements obtained by digital subtraction angiography (DSA) and 2D maximum
      intensity projection (2D-MIP) based on MRA and duplex ultrasonography (US). In 42
      patients undergoing carotid endarterectomy (CEA), intraoperative measurements
      (IOP) were compared with postoperative 3D-MRA and US. RESULTS: Mean interoperator
      variability was 8% for measurements by DSA and 11% by 2D-MIP, but there was no
      interoperator variability with the automated 3D-MRA analysis. Good correlations
      were found between DSA (standard of reference), manual 2D-MIP (rP=0.6) and
      automated 3D-MRA (rP=0.8). Excellent correlations were found between IOP, 3D-MRA
      (rP=0.93) and US (rP=0.83). CONCLUSION: Automated 3D-MRA-based vessel
      segmentation and quantification result in accurate measurements of extracerebral
      vessel dimensions.

PMID- 18707759
TI  - Primary diffuse leptomeningeal gliomatosis.
AB  - A 20-year-old woman with a history of seizures presented symptoms of walking
      difficulties for the past six months. Clinical examination was suggestive of a
      craniovertebral junction anomaly. A cerebrospinal fluid study showed mild protein
      elevation with no evidence of an infective pathology. Craniospinal MRI revealed
      diffuse nodular leptomeningeal enhancement of the brain and spinal cord.
      Histopathological examination was suggestive of a low-grade glioma, and the
      patient was diagnosed with primary diffuse leptomeningeal gliomatosis. So far,
      the patient has survived for more than 110 months without aggressive therapy.

PMID- 18707760
TI  - Template-directed formation of luminescent lanthanide complexes: versatile tools
      for colorimetric identification of single nucleotide polymorphism.
AB  - We present the facile technique of colorimetric SNP (single nucleotide
      polymorphism) analysis through DNA-templated cooperative complexation between a
      luminescent lanthanide ion (Ln(III): Tb(III) or Eu(III)) and two ODN
      (oligodeoxyribonucleotide) conjugates carrying a metal chelator. Families of
      complexane-type chelators and heterocyclic aromatic ligands were covalently
      attached to ODNs to form conjugates for application as capture and sensitizer
      probes. The sequences of the conjugates were designed so as to form a ternary
      tandem duplex with the target, where their auxiliary units face each other,
      providing a microenvironment to accommodate Ln(III). Only the combination of EDTA
      (ethylenediaminetetraacetic acid) conjugates and phen (1,10-phenanthroline)
      conjugates provided significant emissions with quantum yields of 3.3% and 1.5%
      for Tb(III) and Eu(III), respectively, in the presence of the target. Biallelic
      polymorphism in the TPMT (thiopurine S-methyltransferase) gene, wt/wt (G/G),
      mut/mut (C/C), and wt/mut (G/C), were distinguished as emissions in green, red,
      and yellow, respectively; the colors were identified even by the naked eye.

PMID- 18707761
TI  - Synthesis, structures and in vitro cytotoxicity of some platinum(II) complexes
      containing thiocarbamate esters.
AB  - The thiocarbamate esters 4-RC6H4NHC(S)OMe (R = H, Cl, OMe, NO2, Me) react with
      cis-[PtCl2(PTA)2] (PTA=1,3,5-triaza-7-phosphaadamantane) in the presence of base
      to afford the platinum(II) complexes trans-[Pt{SC(OMe)NC6H4R}2(PTA)2] (R=H, Cl,
      OMe, NO2, Me) in high yields. The complexes were fully characterised
      spectroscopically and, in case of the NO2 derivate, by X-ray crystallography.
      Cytotoxicity of these complexes was studied in vitro in four human cancer cell
      lines (CH1, HT29, A549, SK-OV-3) using the MTT assay. The results show that the
      Cl substituted derivate is the most potent of these compounds in vitro. Moreover,
      this derivative is capable of partially circumventing primary cisplatin
      resistance in ovarian and colon carcinoma cells.

PMID- 18707762
TI  - Synthesis and anticancer activity of [2-hydroxy-1,3-diaminopropane-kappa 2N,N']
      platinum(II) complexes.
AB  - A series of novel platinum(II) complexes involving a carrier with HO- peripheral
      functional group, 2-hydroxy-1,3-propanediamine (HO-pda), cis-[Pt(HO-dpa)X(2)]
      (X(2)=2Cl(-) (1), C(2)O(4)(2-) (2), malonate (3), 1,1-cyclobutane dicarboxylate
      (CBDCA) (4), 3-hydroxy-1,1-cyclobutanedicarboxylate (HO-CBDCA) (5)), have been
      synthesized and characterized by elemental analysis and spectroscopic data along
      with X-ray diffraction for three representative complexes 1, 4 and 5. The Pt(II)
      is in a square planar environment and is coordinated in cis position by a
      chelating HO-pda and 2Cl(-) for 1 and CBDCA for 4 and 5. Pt-N, Pt-Cl and Pt-O
      distances and coordinate bond angles of N-Pt-N, Cl-Pt-Cl and O-Pt-O are in the
      normal range. There are two independent molecules in the asymmetric unit of 5,
      held together by intermolecular hydrogen bonded chain. All the complexes show
      significant cytotoxicity on the sensitive cell lines SGC-7901, LNcap and A549,
      and are more active than carboplatin. 4 is also found to be active against the
      resistant cell A549/ATCC, which suggests that it has less cross-resistance with
      cisplatin than carboplatin. Moreover 4 shows much greater inhibition of tumor
      growth than carboplatin in S180-bearing mice, and is therefore worthy of further
      development as a potential anti-tumor platinum drug.

PMID- 18707763
TI  - Resistance to fluoroquinolones and treatment failure/short-term relapse of
      community-acquired urinary tract infections caused by Escherichia coli.
AB  - OBJECTIVES: This study aims to evaluate the impact of resistance to
      fluoroquinolones on the short-term outcome of community-acquired urinary tract
      infections (UTIs) caused by Escherichia coli. METHODS: Patients were identified
      and followed, during 2006, using the health care databases of the Emilia-Romagna
      Region. The outcome of interest was the treatment failure/short-term relapse (the
      re-isolation of E. coli from urine between 4 and 30 days after the first
      isolation). RESULTS: Resistance to fluoroquinolones increases the risk of
      treatment failure/short-term relapse in women with uncomplicated community
      acquired UTIs caused by E. coli (Rate Ratio=1.85, 95% CI 1.32-2.60). The efficacy
      of fluoroquinolones for community-acquired UTIs of men was significantly modified
      by the resistance status of E. coli. Prescription of these agents was associated
      with a reduced occurrence of the outcome only in men with a ciprofloxacin
      sensitive first isolate (Rate Ratio=0.50, 95% CI 0.25-0.99). CONCLUSIONS:
      Resistance to fluoroquinolones of E. coli is a growing problem with a negative
      impact on the outcome of community-acquired UTIs; therefore, the prescription of
      these agents should be limited to infections for which they are recommended,
      avoiding their use in uncomplicated UTIs.

PMID- 18707764
TI  - Treatment of cryptococcal meningitis in Peruvian AIDS patients using amphotericin
      B and fluconazole.
AB  - OBJECTIVES: To describe the mycologic and clinical outcomes and factors
      associated with failure in Peruvian patients with AIDS-associated cryptococcal
      meningitis (CM) treated with amphotericin B deoxycholate (Amph B) followed by
      fluconazole. METHODS: Patients were treated with intravenous Amph B 0.7 mg/kg/day
      for 2 or 3 weeks followed by oral fluconazole 400mg/day for 7 or 8 weeks.
      Clinical and laboratory evaluations including cerebrospinal fluid (CSF) studies
      were performed at baseline and at weeks 2 and 10. RESULTS: The CSF cultures were
      negative in 25% and 68% of 47 patients at weeks 2 and 10, respectively. In the
      univariate analysis, baseline low body mass index (BMI), hyponatremia, low serum
      albumin, positive blood culture and CSF antigen titers >or=1024 were associated
      with a positive CSF culture at week 2. Baseline positive urine culture, positive
      blood culture, any positive extraneural culture and CSF opening pressure at week
      2 >or=300 mm H2O were associated with a positive CSF culture at week 10. In the
      multivariate analysis no association was found. CONCLUSIONS: Therapy with Amph B
      and fluconazole, combined with aggressive management of elevated intracranial
      pressure (ICP), results in low CSF sterilization rates at week 2 and acceptable
      CSF sterilization rates at week 10 when compared with other series.

PMID- 18707765
TI  - Sleep functioning in relation to mood, function, and quality of life at entry to
      the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).
AB  - BACKGROUND: Sleep disturbance in bipolar disorder can be both a risk factor and
      symptom of mood episodes. However, the associations among sleep and clinical
      characteristics, function, and quality of life in bipolar disorder have not been
      fully investigated. METHODS: The prevalence of sleep disturbance, duration, and
      variability, as well as their associations with mood, function, and quality of
      life, was determined from 2024 bipolar patients enrolled in the National
      Institute of Mental Health Systematic Treatment Enhancement Program for Bipolar
      Disorder (STEP-BD). RESULTS: Analyses indicated that 32% of patients were
      classified as short sleepers, 38% normal sleepers, and 23% long sleepers.
      Overall, short sleepers demonstrated greater mood elevation, earlier age at
      onset, and longer illness duration compared to both normal and long sleepers.
      Both short and long sleepers had greater depressive symptoms, poorer life
      functioning, and quality of life compared to normal sleepers. DISCUSSION: Short
      sleep duration in bipolar disorder was associated with a more severe symptom
      presentation, whereas both short and long sleep duration are associated with
      poorer function and quality of life compared to normal sleep duration. Sleep
      disturbance could be a trait marker of bipolar disorder, though longitudinal
      assessments are warranted to assess potential causal relations and the longer
      term implications of sleep disturbance in bipolar disorder.

PMID- 18707767
TI  - Congenital myasthenic syndromes in childhood: diagnostic and management
      challenges.
AB  - The Congenital Myasthenic Syndromes (CMS), a group of heterogeneous genetic
      disorders of neuromuscular transmission, are often misdiagnosed as congenital
      muscular dystrophy (CMD) or myopathies and present particular management
      problems. We present our experience of 46 children with CMS, referred to us
      between 1992-2007 with provisional diagnoses of congenital myopathy (22/46), CMS
      or limb-girdle myasthenia (9/46), central hypotonia or neurometabolic disease
      (5/46), myasthenia gravis (4/46), limb-girdle or congenital muscular dystrophy
      (4/46) and SMA (2/46). Diagnosis was often considerably delayed (up to 18y4 m),
      despite the early symptoms in most cases. Diagnostic clues in the neonates were
      feeding difficulties (29/46), hypotonia with or without limb weakness (21/46),
      ptosis (19/46), respiratory insufficiency (12/46), contractures (4/46) and
      stridor (6/46). Twenty-five children had delayed motor milestones. Fatigability
      developed in 43 and a variable degree of ptosis was eventually present in 40.
      Over the period of the study, the mainstay of EMG diagnosis evolved from
      repetitive nerve stimulation to stimulation single fibre EMG. The patients were
      studied by several different operators. 66 EMGs were performed in 40 children, 29
      showed a neuromuscular junction abnormality, 7 were myopathic, 2 had possible
      neurogenic changes and 28 were normal or inconclusive. A repetitive CMAP was
      detected in only one of seven children with a COLQ mutation and neither of the
      two children with Slow Channel Syndrome mutations. Mutations have been identified
      so far in 32/46 children: 10 RAPSN, 7 COLQ, 6 CHRNE, 7 DOK7, 1 CHRNA1 and 1 CHAT.
      24 of 25 muscle biopsies showed myopathic changes with fibre size variation; 14
      had type-1 fibre predominance. Three cases showed small type-1 fibres resembling
      fibre type disproportion, and four showed core-like lesions. No specific
      myopathic features were associated with any of the genes. Twenty children
      responded to Pyridostigmine treatment alone, 11 to Pyridostigmine with either 3,
      4 DAP or Ephedrine and five to Ephedrine alone. Twenty one children required
      acute or chronic respiratory support, with tracheostomy in 4 and nocturnal or
      emergency non-invasive ventilation in 9. Eight children had gastrostomy. Another
      11 were underweight for height indicative of failure to thrive and required
      dietetic input. A high index of clinical suspicion, repeat EMG by an experienced
      electromyographer and, if necessary, a therapeutic trial of Pyridostigmine
      facilitates the diagnosis of CMS with subsequent molecular genetic confirmation.
      This guides rational therapy and multidisciplinary management, which may be
      crucial for survival, particularly in pedigrees where previous deaths have
      occurred in infancy.

PMID- 18707766
TI  - Lifetime criminality among boys with attention deficit hyperactivity disorder: a
      prospective follow-up study into adulthood using official arrest records.
AB  - This study investigates the relationship between childhood attention deficit
      hyperactivity disorder (ADHD) and later criminality. White boys (n=207, ages 6
      12) with ADHD, free of conduct disorder, were assessed at ages 18 and 25 by
      clinicians who were blind to childhood status. A non-ADHD group served as
      comparisons. Lifetime arrest records were obtained when subjects were 38 years
      old for subjects who resided in New York State throughout the follow-up interval
      (93 probands, 93 comparisons). Significantly more ADHD probands than comparisons
      had been arrested (47% vs. 24%), convicted (42% vs. 14%), and incarcerated (15%
      vs. 1%). Rates of felonies and aggressive offenses also were significantly higher
      among probands. Importantly, the development of an antisocial or substance use
      disorder in adolescence completely explained the increased risk for subsequent
      criminality. Results suggest that even in the absence of comorbid conduct
      disorder in childhood, ADHD increases the risk for developing antisocial and
      substance use disorders in adolescence, which, in turn, increases the risk for
      criminal behavior in adolescence and adulthood.

PMID- 18707769
TI  - Does stimulation of 5-HT(1A) receptors improve cognition in schizophrenia?
AB  - Cognitive impairment is a key feature of schizophrenia and may be the most
      important determinant of outcome in schizophrenia. This impairment is diffuse and
      may reflect abnormalities in frontal cortex, hippocampus and other brain regions.
      While deficits in glutamatergic, GABAergic, dopaminergic and cholinergic
      impairment have received the most attention as the basis of this impairment,
      there are many reasons for considering the role of serotonin (5-HT) in
      contributing to these deficits. This may be via its influence on dopaminergic,
      cholinergic, glutamatergic and GABAergic function, as well as various growth
      factors that have been implicated in schizophrenia. Of the 14 known serotonin
      receptors, the 5-HT(1A) receptor is a key candidate for mediating at least some
      of the influence 5-HT has on cognition. 5-HT(1A) receptors are upregulated in
      postmortem specimens from patients with schizophrenia, suggesting a deficit in 5
      HT(1A) function in this disorder. Atypical but not typical antipsychotic drugs
      stimulate the efflux of dopamine from cortex by a 5-HT(1A)-dependent mechanism. A
      series of studies from this laboratory involving the 5-HT(1A) partial agonists
      tandospirone and buspirone have reported a modest ability of these agents to
      improve some domains of cognition in patients receiving typical or atypical
      antipsychotic drugs. Preclinical studies have been mixed in regard to the ability
      of 5-HT(1A) partial agonists to improve cognition in various paradigms; some
      studies report that 5-HT(1A) antagonists are effective to improve cognition.
      Aripiprazole, clozapine, olanzapine, perospirone, quetiapine risperidone, and
      ziprasidone are examples of atypical antipsychotic drugs which are either direct
      or indirect 5-HT(1A) agonists which have been shown to improve cognitive function
      in patients with schizophrenia. Further study is needed to determine the role of
      the 5-HT(1A) receptor to improve cognitive function in schizophrenia.

PMID- 18707770
TI  - Long-term follow-up of mitral valve regurgitation--importance of mitral valve
      pathology and left ventricular function on survival.
AB  - BACKGROUND: Timing of surgery for mitral regurgitation (MR) is one of the more
      difficult decisions for the practicing cardiologist. METHODS AND RESULTS: In
      order to determine useful clinical cut-offs, we investigated the influence of
      baseline echocardiographic predictors for survival in a long-time follow-up
      cohort. Data from 144 patients with MR were collected between 1989 and 1993. Five
      year mortality for MR patients was 30% compared to 13% for age- and sex matched
      controls (p<0.001). Each mm increase in left ventricular end systolic diameter
      (LVESD increased mortality with 2.5% (p<0.05) and each percent decrease in
      ejection fraction (EF) increased mortality with 1.8% (p<0.05). These effects were
      not linear and this material suggests cut-off points for LVESD to be 40 mm and EF
      50%. Degree of MR did not correlate with survival, but patients with severe MR
      were operated more often than those with moderate MR. Patients with functional MR
      had reduced survival compared to patients with structural MR (p<0.01).
      CONCLUSIONS: MR is a disease with greatly increased mortality and these data
      suggest a more aggressive approach to surgery.

PMID- 18707771
TI  - Osteoprotegerin and B-type natriuretic peptide in acute coronary syndromes with
      preserved systolic function: relation to coronary artery disease extension.
AB  - OBJECTIVES: To analyze Osteoprotegerin (OPG), and BNP plasma levels in patients
      with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical
      presentation and to coronary atherosclerosis diffusion. METHODS: 155 CAD patients
      were classified in four groups: stable angina (SA n=42), unstable angina (UA
      n=35) non-ST elevation myocardial infarction (NSTEMI n=45) and control group
      (n=33), measuring OPG and BNP at hospital admission. We compared both biomarkers
      in relation to the number of coronary narrowed vessels (1-,2-,3 or more vessels
      disease), and to the stenoses degree by Duke Jeopardy score. RESULTS: OPG levels
      were higher in patients with CAD respect to controls (p<0.0001). Patients with SA
      showed more elevated levels than controls (2.6+/-1.2 vs 7.4+/-5.0 pmol/l p<0.01).
      However patients with UA and NSTEMI had higher OPG level with respect to SA
      patients (12.2+/-7.8 and 11.6+/-6.1 respectively pmol/l p<0.001). A positive
      relation was found between OPG levels and coronary plaques extension by Duke
      Jeopardy score (r=0.65). BNP levels were higher in patients with UA/NSTEMI
      respect to controls and SA patients (p<0.001). Besides, BNP was significantly
      higher in patients with multi-vessels vs 1-vessel disease (p<0.001). CONCLUSIONS:
      Patients with UA and NSTEMI show high OPG and BNP levels. OPG increase seems
      related to the number of plaques in the coronary vessels, suggesting its
      involvement in the CAD progression.

PMID- 18707772
TI  - Post-PCI fatal bleeding in aspirin and clopidogrel hyper responder: shifting from
      antiplatelet resistance to bleeding risk assessment?
AB  - A 64 year old woman with previous history of coronary stenting five days before
      was admitted in our institution for intracranial bleeding while receiving aspirin
      and clopidogrel. At hospital discharge, platelet testing showed hyper response to
      antiplatelet therapy with very low post treatment platelet reactivity.

PMID- 18707773
TI  - An anomalous right coronary artery originating from the mid portion of the left
      descending artery.
AB  - We report on a 76-year old patient in which a very rare coronary anomaly was
      found.

PMID- 18707774
TI  - Is mitral regurgitant jet offensive rather than protective for left atrial
      thrombus?

PMID- 18707775
TI  - Cardiovascular risk factors in the Japanese northeastern rural population.
AB  - BACKGROUND: People living in the northeastern part of Japan have high prevalences
      of hypertension and stroke. The current status of cardiovascular risk factors in
      them should be elucidated. METHODS: The survey was carried out from 2002 to 2004
      in the northeastern part of the main island of Japan. A total of 26,472 Japanese
      men and women were enrolled (acceptance rate: 84.5%). Sex- and age-specific
      prevalences of cardiovascular risk factors were determined. Mean values of
      predictive markers (high-sensitivity C reactive protein (hsCRP), brain
      natriuretic peptide (BNP) and microalbuminuria) were also determined in each
      group. Risk factor-related variables in non-hypertensive subjects and
      hypertensive subjects were compared. RESULTS: Proportions of subjects with
      hypertension, diabetes and dyslipidemia were 46.0%, 7.6%, and 30.3%,
      respectively, in males and 38.6%, 4.0%, and 38.5%, respectively, in females. Mean
      values of hsCRP and BNP were 1.41 mg/L and 26.5 pg/mL, respectively, in males and
      1.01 mg/L and 23.7 pg/mL, respectively, in females. Proportions of male and
      female subjects with microalbuminuria were 22.0% and 23.4%, respectively. These
      markers become higher with advance of age. Prevalence of atrial fibrillation was
      1.56%, and it increased with advance of age in both men and women. High
      prevalences of cardiovascular risk factors in this area were found. Hypertensive
      subjects who did not take anti-hypertension medication accounted for about 20% of
      total subjects and their blood pressure remained poorly controlled. CONCLUSION:
      Attention should be given to cardiovascular risk factors in the Japanese
      northeastern rural population.

PMID- 18707776
TI  - Depression and anxiety in adult congenital heart disease: predictors and
      prevalence.
AB  - BACKGROUND: Adult congenital heart disease (ACHD) patients face unique medical
      and social challenges that may contribute to psychological difficulties. The
      goals of this study were to identify predictors of symptoms of depression and
      anxiety and evaluate the prevalence of mood and anxiety disorders among North
      American ACHD patients. METHODS: In this cross-sectional study, consecutive
      patients were recruited from two ACHD outpatient clinics. All patients completed
      self-report psychosocial measures and a subset was randomly selected to
      participate in structured clinical interviews. Linear regression models were used
      to predict symptoms of depression and anxiety. RESULTS: A total of 280 patients
      (mean age=32 years; 52% female) completed self-report measures. Sixty percent had
      defects of moderate complexity and 31% had defects of great complexity.
      Significant predictors of depressive symptoms were loneliness (p<0.001),
      perceived health status (p<0.001), and fear of negative evaluation (p=0.02).
      Predictors of anxiety symptoms were loneliness (p<0.001) and fear of negative
      evaluation (p<0.001). Disease severity and functional class did not predict mood
      or anxiety symptoms. Fifty percent of interviewed patients (29/58) met diagnostic
      criteria for at least one lifetime mood or anxiety disorder, of whom 39% had
      never received any mental health treatment. CONCLUSIONS: The results confirm an
      increased risk and under-treatment of mood and anxiety disorders in ACHD
      patients. Social adjustment and patient-perceived health status were more
      predictive of depression and anxiety than medical variables. These factors are
      modifiable and therefore a potential focus of intervention.

PMID- 18707777
TI  - Coffee consumption and risk of coronary heart diseases: a meta-analysis of 21
      prospective cohort studies.
AB  - BACKGROUND: A large amount of cohort studies addressed coffee consumption and
      risk of coronary heart disease (CHD) and yielded inconsistent results. We
      conducted a meta-analysis to estimate the pooling effects. METHODS: We searched
      for all published English articles indexed in MEDLINE or PubMed from January 1966
      to January 2008. Twenty-one independent prospective cohort studies, which tested
      CHD risk by coffee consumption, were identified. A general variance-based method
      was used to pool the relative risks (RR). 15,599 cases from 407,806 participants
      were included in pooling the overall effects. RESULTS: As compared to the light
      coffee consumption (<1 cup/d in US or <or=2 cups/d in Europe), under the random
      effects model, the pooled CHD RRs (95% CI) for all studies combined were 0.96
      (0.87-1.06), 1.04 (0.92-1.17) and 1.07 (0.87-1.32) for the moderate (1-3 or 3-4
      cups/d), heavy (4-5 or 5-6 cups/d) and very heavy (>or=6 or >or=7 cups/d)
      categories of coffee consumption (all p>0.05); Moderate coffee consumption showed
      significantly lower CHD RR (95% CI) of 0.82 (0.73-0.92) (p<0.001) in women, and
      of 0.87 (0.80-0.86) (p=0.001) in men and women followed <or=10 years. CONCLUSION:
      Our findings do not support the hypothesis that coffee consumption increases the
      long-term risk of coronary heart disease. Habitual moderate coffee drinking was
      associated with a lower risk of CHD in women.

PMID- 18707778
TI  - Transient left ventricular ballooning (tako-tsubo cardiomyopathy) soon after
      intravenous ergonovine injection following caesarean delivery.
AB  - Transient left ventricular ballooning also called tako-tsubo syndrome, is
      increasingly being recognized as cardiomyopathy mimicking the clinical scenario
      of an acute myocardial infarction. Generally, it is characterized by apical
      ballooning appearance of the left ventricle in the presence of normal coronary
      arteries on the angiogram. Recently, a variant form involving the midventricle
      with sparing of the apical and basal segments has been described. This syndrome
      is more prevalent in postmenopausal woman and usually preceded by extreme
      emotional and/or physical stress. We describe a case never reported before of
      transient left ventricular ballooning occurring during the early postpartum
      period after ergonovine injection rapidly evolving from a 'typical apical'
      ballooning into a 'midventricular' myocardial dysfunction.

PMID- 18707779
TI  - Stress cardiomyopathy with ST-segment elevation of the anterolateral location
      complicated by a secondary massive intracranial bleeding.
AB  - Stress cardiomyopathy or Tako-Tsubo Syndrome (TTS) clinically manifests with
      sudden chest pain and/or dyspnea, and is generally triggered by emotional or
      physical stress. Electrocardiographic (ECG) changes are similar to acute
      myocardial infarction with ST-elevation, but coronarography shows no significant
      pathomorphological changes of coronary arteries. Ventriculography and
      echocardiography show reversible akinesis and ballooning of the left ventricle
      apex with reduced ejection fraction. Like as it is with TTS, similar ECG changes
      are extensively reported in patients with intracerebral bleeding. We reported the
      case of a 52-year-old female patient who was clinically presented with stress
      cardiomyopathy with ST-segment elevation of the anterolateral location
      complicated by a secondary massive intracranial bleeding. Many cases of TTS or
      ECG changes in intracranial bleeding were described separately, but to our
      knowledge, this is the first report where both events developed in the same
      patient with the fatal outcome.

PMID- 18707781
TI  - Has public health insurance for older children reduced disparities in access to
      care and health outcomes?
AB  - This paper investigates the effects of expanding public health insurance
      eligibility for older children. Using data from the National Health Interview
      Surveys from 1986 to 2005, we first show that although income continues to be an
      important predictor of children's health status, the importance of income for
      predicting health has fallen for children 9-17 in recent years. We then
      investigate the extent to which the dramatic expansions in public health
      insurance coverage for these children in the past decade are responsible for the
      decline in the importance of income. We find that while eligibility for public
      health insurance unambiguously improves current utilization of preventive care,
      it has little effect on current health status. However, we find some evidence
      that Medicaid eligibility in early childhood has positive effects on future
      health. This may indicate that adequate medical care early on puts children on a
      better health trajectory, resulting in better health as they grow.

PMID- 18707782
TI  - The effect of amifostine or IMRT to preserve the parotid function after
      radiotherapy of the head and neck region measured by quantitative salivary gland
      scintigraphy.
AB  - PURPOSE: In this retrospective study, two approaches to preserve the parotid
      function after radiotherapy (RT) were compared: application of the
      radioprotective agent amifostine during RT and parotid-sparing intensity
      modulated radiotherapy (IMRT). PATIENTS AND METHODS: Patients were qualified for
      this analysis if (1) both parotid glands received a radiation dose of >or=50Gy
      using conventional radiotherapy techniques (cRT) or if they received a parotid
      sparing IMRT as alternative, if (2) salivary gland scintigraphies before and
      after RT were performed, and if (3) a normal parotid function was present before
      RT. Quantitative salivary gland scintigraphy was used to assess the parotid gland
      function. RESULTS: Altogether 275 salivary gland scintigraphies of 100 patients
      were analyzed. The mean relative tracer uptake (DeltaU) of patients treated with
      cRT, cRT with amifostine and IMRT 1-12 months after RT was 0.59 (95%CI 0.54
      0.65), 0.67 (95%CI 0.59-0.76), and 0.93 (95%CI 0.78-1.07), respectively. The mean
      relative DeltaU 13-47 months after RT was 0.40 (95%CI 0.32-0.49), 0.60 (95%CI
      0.48-0.71), and 0.92 (95%CI 0.56-1.28). At 1-12 months after RT, ANOVA testing
      with post-hoc comparison using the Bonferroni correction showed a significant
      difference between IMRT and cRT (p<0.001) or IMRT and amifostine (p<0.01). The
      difference between amifostine and cRT was not significant during the first year.
      At 13-47 months after RT, the difference between cRT and amifostine was
      significant (p=0.02). CONCLUSION: Our data suggest that both amifostine and IMRT
      are able to partially preserve the parotid function after radiotherapy. The
      effect of IMRT appeared to be much greater.

PMID- 18707783
TI  - Second cancers in children treated with modern radiotherapy techniques.
AB  - BACKGROUND AND PURPOSE: The scattered radiation from the treatment volume might
      be more significant for children than for adults and, as a consequence, modern
      radiotherapy treatment techniques such as IMRT and passive proton therapy could
      potentially increase the number of secondary cancers. In this report, secondary
      cancer risk resulting from new treatment technologies was estimated for an adult
      prostate patient and a child. MATERIAL AND METHODS: The organ equivalent dose
      (OED) concept with a linear-exponential, a plateau and a linear dose-response
      curve was applied to dose distributions of an adult prostate patient and a child
      with a rhabdomyosarcoma of the prostate. Conformal radiotherapy, IMRT with 6MV
      photons and proton therapy were planned. OED (cancer risk) was estimated for the
      whole body, the rectum and the bladder. In addition, relative cumulative risk was
      calculated. RESULTS: Secondary cancer risk in the adult is not more than 15% it
      increased when IMRT or passive proton therapy was compared to conventional
      treatment planning. In the child, risk remains practically constant or was even
      reduced for proton therapy. The cumulative risk in the child relative to that in
      the adult can be as large as 10-15. CONCLUSIONS: By a comparison between an adult
      patient and a child treated for a disease of the prostate, it was shown that
      modern radiotherapy techniques such as IMRT and proton therapy (active and
      passive) do not increase the risk for secondary cancers.

PMID- 18707784
TI  - Cost-effectiveness of particle therapy: current evidence and future needs.
AB  - PURPOSE: Questions are being raised regarding the cost of particle therapy (PT),
      and with them criticism that PT is too expensive to allow the expected gain in
      effectiveness. This paper aims to get more insight in the cost and cost
      effectiveness of particle therapy and to discuss a future strategy that allows
      for critical assessment of this health technology. MATERIAL AND METHODS: A
      systematic literature review based on an earlier published comprehensive review
      was performed and updated until June 1st 2008. Besides, current business plans of
      PT projects were examined. Additionally, results retrieved from a cost-simulation
      tool developed under auspice of the ENLIGHT were discussed. RESULTS: The current
      literature on cost-effectiveness of PT is scarce, non-comparable, and largely not
      performed according to standard health technology assessment criteria. Besides,
      different perspectives for cost evaluations have been used, making it difficult
      to compare and to determine the relative impact in terms of costs for this new
      treatment modality. CONCLUSIONS: Evidence on the cost-effectiveness of PT is
      scarce. Adequate reimbursement is necessary to support such innovative yet costly
      treatments. For now, model-based economic evaluations performed at least from a
      health care perspective may help us to gain evidence-based insight into cost
      effectiveness.

PMID- 18707785
TI  - Impact of the boost dose of 10 Gy versus 26 Gy in patients with early stage
      breast cancer after a microscopically incomplete lumpectomy: 10-year results of
      the randomised EORTC boost trial.
AB  - PURPOSE: To assess the impact of the boost dose in patients with involved
      surgical margins. PATIENTS AND METHODS: In the EORTC "boost versus no boost"
      trial, 251 patients with a microscopically incomplete tumour excision were
      randomised to receive either a low boost dose of 10 Gy (126 patients) or a high
      boost dose of 26 Gy (125 patients). Overall survival and the cumulative incidence
      of local recurrence as first event were compared by Logrank and Gray test,
      respectively (2-sided alpha=0.05), with a median follow-up of 11.3 years. The
      planned sample size was 660 patients, but only 251 were recruited. RESULTS: The
      median age at randomisation was 54 years. Thirty-seven patient initially relapsed
      locally. At 10 years, the cumulative incidence of local recurrence was 17.5% (95%
      CI: 10.4-24.6%) versus 10.8% (95% CI: 5.2-16.4%) for the low and high boost dose
      groups, respectively (HR=0.83, 95% CI: 0.43-1.57, Gray p>0.1). Overall, 64
      patients have died (25.5%), 47 of them of breast cancer, without a difference in
      duration of survival between the two groups (HR=0.97, 95% CI=0.59-1.5, p>0.1).
      Severe fibrosis was palpated in the breast in 1% versus 5% and in the boost area
      in 3% versus 13% in the low and high boost dose groups, respectively.
      CONCLUSIONS: There was no statistically significant difference in local control
      or survival between the high boost dose of 26 Gy and the low boost dose of 10 Gy
      in patients with microscopically incomplete excision of early breast cancer.
      Fibrosis, however, was noted significantly more frequently in cases treated with
      the high boost dose.

PMID- 18707786
TI  - Evaluation of geometric changes of parotid glands during head and neck cancer
      radiotherapy using daily MVCT and automatic deformable registration.
AB  - BACKGROUND AND PURPOSE: To assess and evaluate geometrical changes in parotid
      glands using deformable image registration and megavoltage CT (MVCT) images.
      METHODS: A deformable registration algorithm was applied to 330 daily MVCT images
      (10 patients) to create deformed parotid contours. The accuracy and robustness of
      the algorithm was evaluated through visual review, comparison with manual
      contours, and precision analysis. Temporal changes in the parotid gland geometry
      were observed. RESULTS: The deformed parotid contours were qualitatively judged
      to be acceptable. Compared with manual contours, the uncertainties of
      automatically deformed contours were similar with regard to geometry and
      dosimetric endpoint. The day-to-day variations (1 standard deviation of errors)
      in the center-of-mass distance and volume were 1.61mm and 4.36%, respectively.
      The volumes tended to decrease with a median total loss of 21.3% (6.7-31.5%) and
      a median change rate of 0.7%/day (0.4-1.3%/day). Parotids migrated toward the
      patient center with a median total distance change of -5.26mm (0.00 to -16.35mm)
      and a median change rate of -0.22mm/day (0.02 to -0.56mm/day). CONCLUSION: The
      deformable image registration and daily MVCT images provide an efficient and
      reliable assessment of parotid changes over the course of a radiation therapy.

PMID- 18707788
TI  - Genotyping by Amplified Fragment Length Polymorphism and malate metabolism
      performances of indigenous Oenococcus oeni strains isolated from Primitivo wine.
AB  - The Amplified Fragment Length Polymorphism (AFLP) technique was applied for the
      first time to investigate the genotyping of Oenococcus oeni, the most important
      species involved in malolactic fermentation (MLF) in wine. A total of 87 out of
      220 lactic acid bacteria, isolates from "Primitivo" wine (Apulia, Italy)
      undergoing MLF, identified as O. oeni by species-specific PCR and 16S rRNA
      sequence analysis, were studied by AFLP analysis. Four main clusters were
      distinguished and three of them showed intraspecific homology higher than 60%. A
      total of 28 strains, representative of AFLP clusters, were tested for malate
      metabolism in order to gain information on their malolactic performances.
      Significant differences were observed among strains for malic acid consumed,
      biomass produced and specific malic acid consumption rate. These findings
      indicated that AFLP technique is reliable for typing O. oeni strains and that,
      together with metabolism studies it may be used to individuate possible
      candidates as industrial malolactic starters.

PMID- 18707787
TI  - Prevalence and characterization of Salmonella infantis isolates originating from
      different points of the broiler chicken-human food chain in Hungary.
AB  - During the 10-month study period Salmonella contamination of broiler houses and
      the flocks reared in three farms (A, B and C), the slaughter houses where the
      flocks were slaughtered, as well as the carcass and retail raw meat products
      originating from them was investigated. In the broiler farm A five consecutive
      flocks, in the B and C farms one flock was sampled. Environmental samples were
      taken prior to the introductions. Environmental, drinking water, feed and faecal
      samples were collected regularly using standard methods. Before and during
      processing of the flocks, environmental and carcass samples were taken at the
      abattoirs. Salmonella contamination of the carcass, retail meat, as well as stool
      samples of farm and abattoir workers and from human illnesses registered in the
      same period and region were also examined. Isolation, sero-, phage- and
      antibiotic resistance typing, class 1 integron and plasmid profiling of the
      strains were performed; their genetic relationship was assessed by PFGE. Although
      the broiler house and the faecal samples of the 5 flocks of the farm A were
      negative for Salmonella, S. infantis was isolated from 20-100% of the abattoir
      carcass samples. The retail raw meat samples were 0-100% S. infantis positive.
      The environmental samples of farm B were Salmonella negative, but the examined
      flock was contaminated: S. infantis was identified from 43% of the faecal
      samples. This serotype was identified in 100% of the carcass and retail raw meat
      samples. From environmental samples taken before the arrival of the 1-day-old
      chicks in the broiler house C, S. infantis was cultured. S. infantis prevalence
      in the faecal samples was 35% and all the carcass and retail raw meat samples
      were S. infantis contaminated. Altogether 164 S. infantis strains were isolated
      out of which 145 were further characterized. The vast majority (142/145) of the
      strains belonged to phage types 217 and 213. All but one were characterized by
      the nalidixic acid-streptomycin-sulphonamide-tetracycline resistances, had an 885
      bp class 1 integron and a large plasmid of > 168 kb in size. The strains showed >
      or = 88.7% genetic similarity. The results obtained shows that the same multi
      drug resistant S. infantis clone was spread from the examined broiler farms
      contaminating the slaughter and the retail meat and appeared in the human
      illnesses of the examined region that was earlier detected as the dominant clone
      characteristic of the broiler and human population of the whole country.

PMID- 18707789
TI  - Effectiveness of chitosan-coated plastic films incorporating antimicrobials in
      inhibition of Listeria monocytogenes on cold-smoked salmon.
AB  - The objective of this study was to evaluate the efficacy of chitosan-coated
      plastic films incorporating five Generally Recognized as Safe (GRAS)
      antimicrobials (nisin, sodium lactate (SL), sodium diacetate (SD), potassium
      sorbate (PS) and sodium benzoate (SB)) against Listeria monocytogenes on cold
      smoked salmon. Salmon samples were surface-inoculated with a five-strain cocktail
      of L. monocytogenes and packaged in chitosan-coated plastic films containing 500
      IU/cm(2) of nisin, 9 mg/cm(2) of SL, 0.5 mg/cm(2) of SD, 0.6 mg/cm(2) of PS, or
      0.2 mg/cm(2) of SB, and stored at room temperature (ca. 20 degrees C) for 10
      days. The film incorporating SL was the most effective, completely inhibiting the
      growth of L. monocytogenes during 10 days of storage. L. monocytogenes in samples
      packaged in the other four antimicrobial films grew, but the increase in counts
      was lower than the control. The antilisterial efficacy of films containing lower
      concentrations of SL (2.3 mg/cm(2) and 4.5 mg/cm(2)) and binary combinations SL,
      PS, SD, SB and nisin were subsequently evaluated. Among all the treatments,
      chitosan-coated plastic films with 4.5 mg/cm(2) SL, 4.5 mg/cm(2) SL-0.6 mg/cm(2)
      PS and 2.3 mg/cm(2) SL-500 IU/cm(2) nisin were the most effective. These three
      most effective antimicrobial films were then tested at refrigerated temperature.
      They completely inhibited the growth of L. monocytogenes on smoked salmon for at
      least 6 weeks. Chitosan-coated plastic films containing 4.5 mg/cm(2) SL can
      potentially assist the smoked-salmon processing industry in their efforts to
      control L. monocytogenes.

PMID- 18707790
TI  - Time-course changes in clinical features of early-onset Japanese type 1 and type
      2 diabetes: TWMU hospital-based study.
AB  - Using a database of patients with type 1 (n=1675) and type 2 (n=2259) diabetes
      diagnosed before the age of 30 years at the Diabetes Center, Tokyo Women's
      Medical University (TWMU), in which such Japanese patients have been registered
      at the time of first visit since the 1960s, we performed a hospital-based study
      over the last 40 years to clarify time-course changes in clinical features of
      type 1 and type 2 diabetes diagnosed before the age of 30 years. Type 2 diabetes
      had a male dominancy, while there has been a female dominancy in patients with
      type 1 diabetes as in previous reports of Japanese childhood-onset type 1
      diabetes. Such dominances had been continued over the last 40 years. The number
      of patients with type 2 diabetes and with a past history of obesity increased
      with time. The age at which type 2 diabetes was diagnosed was suggested to have
      been getting lower with time, whereas that of type 1 diabetes has been higher
      with time. There was no marked difference in family history of diabetes in the
      first-degree relatives of patients with type 2 diabetes, regardless of the
      presence or absence of a past history of obesity. More female patients with type
      2 diabetes diagnosed before the age of 15 years had mothers with type 2 diabetes
      compared to corresponding male patients.

PMID- 18707792
TI  - Nonlinear dynamics analysis of electrocardiograms for detection of coronary
      artery disease.
AB  - A computerized approach of nonlinear dynamics analysis of electrocardiogram (ECG)
      signals was applied for the detection of coronary artery disease (CAD). The
      proposed nonlinear dynamics descriptors were derived from 12-lead rest ECG data,
      and evaluated by originally developed computer software. Fluctuations of
      potentials of ECG leads that occur during the period of 20 ms with a magnitude of
      5-20 microV were significantly less beat-to-beat predictable in ischemic versus
      non-ischemic patients. The well-known nonlinear dynamics descriptors, recurrences
      percentage, mutual information, fractal dimension, and a new descriptor, next
      embedding dimension error, were good quantitative descriptors of fluctuations.
      They were significantly different (< p = 0.00001) in males with (108 patients)
      and without (54 patients) coronary artery lesions. The analysis of small
      fluctuations required a careful preprocessing technique based on knowledge of
      specifics of measurement errors and physiology of ECG signals. We considered
      finite differences of measured potentials with the time step of 20 ms as the
      initial source for nonlinear analysis. In nonlinear dynamics analysis, we also
      included such time moments that only belong to P- and T-waves or baseline drift
      with small positive slopes that allowed us to extract, under normal conditions,
      initial halves of P- and T-waves that displayed a better capacity to classify
      ischemic patients.

PMID- 18707791
TI  - The genetics of hyperekplexia: more than startle!
AB  - Hyperekplexia is characterised by neonatal hypertonia and an exaggerated startle
      reflex in response to acoustic or tactile stimuli. Genetic analysis of this
      disorder has revealed mutations in genes for several postsynaptic proteins
      involved in glycinergic neurotransmission, including the glycine receptor (GlyR)
      alpha1 and beta subunits, gephyrin and collybistin. However, new research
      suggests that mutations in the gene encoding the presynaptic glycine transporter
      GlyT2 are a second major cause of human hyperekplexia, as well as congenital
      muscular dystonia type 2 (CMD2) in cattle. These findings raise the intriguing
      possibility that both presynaptic and postsynaptic causes of disease might also
      exist in related disorders, such as idiopathic generalised epilepsies, where
      mutations in inhibitory GABA(A) receptor subunit genes have already been
      identified.

PMID- 18707793
TI  - The profilin:actin complex localizes to sites of dynamic actin polymerization at
      the leading edge of migrating cells and pathogen-induced actin tails.
AB  - A unique set of affinity-purified anti-profilin and anti-actin antibodies
      generated against a covalently coupled version of the profilin:actin complex was
      used to assess the distribution of profilin and non-filamentous actin in mouse
      melanoma cells. In agreement with the profilin:actin complex being the principal
      source of actin for filament formation, we observed extensive co-distribution of
      both antibody preparations with vasodilator-stimulated phosphoprotein (VASP) and
      the p34 subunit of the Arp2/3 complex, both of which are components of actin
      polymer-forming protein complexes in the cell. This suggests that the
      localization of profilin and actin revealed with these antibodies in fact
      reflects the distribution of the profilin:actin complex rather than the two
      proteins separately. Significantly, protruding lamellipodia and filopodia showed
      intensive labeling. The two antibody preparations were also used to stain HeLa
      cells infected with Listeria monocytogenes or vaccinia virus. In both cases, the
      pattern of antibody staining of the pathogen-induced microfilament arrangement
      differed, suggesting a varying accessibility for the antibody-binding epitopes.

PMID- 18707794
TI  - Divalent cation distribution in dinoflagellate chromosomes imaged by high
      resolution ion probe mass spectrometry.
AB  - From a variety of analytical electron microscopy experiments, the chromosomes of
      dinoflagellates are known to contain sizeable amounts of cations, the latter
      thought to contribute to the neutralization of the negative charge carried by the
      phosphate groups in the DNA backbone. From previous Ca and Mg chelation
      experiments, it is also known that these cations are necessary for the compaction
      and preservation of the chromosome architecture. Similar conclusions have been
      recently presented by our group concerning mammalian mitotic chromosomes, in
      studies based on secondary ion mass spectrometry (SIMS) carried out with the
      University of Chicago high-resolution scanning ion microprobe (UC-SIM). We have
      now applied this instrument to image the distribution of DNA-bound Ca(2+) and
      Mg(2+) in dinoflagellate chromosomes, a goal that could not be attained earlier
      by analytical electron microscopy. Analyzed quantitatively and imaged here by
      SIMS for the first time, through their cation content, are the chromosomes of the
      dinoflagellates Prorocentrum micans, Gymnodinium mikimotoi and Gymnodinium
      dorsum. The cell nuclei were isolated and prepared for SIMS analysis with a
      minimal protocol (mechanical fractionation in culture medium followed by ethanol
      drying), which did not expose the samples to artifact-creating, alien chemical
      agents. By this approach, we have confirmed the earlier findings by several
      authors, and contributed new structural information provided by our ion probe
      capability to erode the sample surface layer by layer (SIMS tomography).
      Dinoflagellates, due to the absence of histones, represent an ideal model system
      where cations may bind directly with DNA, allowing comparisons to be made with
      recently reported X-ray crystallography results at atomic resolution. Such
      comparisons yielded quantitative confirmation that the Ca(2+)+Mg(2+)
      concentrations found for e.g. P. micans are consistent with those anticipated to
      provide complete charge neutralization of naked DNA by cations, also resulting in
      maximal DNA compaction.

PMID- 18707795
TI  - Pathophysiological roles of osteoprotegerin (OPG).
AB  - Osteoprotegerin (OPG) is a secreted glycoprotein central to bone turnover via its
      role as a decoy receptor for the receptor activator of nuclear factor kappaB
      ligand (RANKL) and has traditionally been linked to a number of bone-related
      diseases. However, there is additional evidence that OPG can promote cell
      survival by inhibiting TNF-related apoptosis-inducing ligand (TRAIL)-induced
      apoptosis. As a result, a number of in vitro, in vivo and clinical studies have
      been performed assessing the role of OPG in tumourigenesis. Similar studies have
      been performed regarding vascular pathologies, resulting from observations of
      expression and regulation of OPG in the vasculature. This review aims to provide
      an update on this area and assess the potential protective or detrimental role of
      OPG in both vascular pathologies and tumourigenesis.

PMID- 18707796
TI  - Analysis of clock gene homologs using unifoliolates as target organs in soybean
      (Glycine max).
AB  - Soybean is a typical short-day crop, and its photoperiodic response of flowering
      is critical to its yield. This phenomenon was well studied during the last
      century, but the molecular mechanism governing it is unknown. The clock-gene
      homologs, GmLCL1 and GmLCL2 (Glycine max LHY/CCA1 Like 1 and 2) and GmTOC1
      (Glycine max TOC1) were cloned from Glycine max L. KN18, and their expression
      patterns were analyzed using a system developed in this study. We employed 8h
      light/16h dark and 18h light/6h dark as short- and long-day conditions,
      respectively, because in these conditions soybean plants had significant indexes
      of flowering time. We also used unifoliolates, not the whole plant as
      Arabidopsis, as target organs for gene expression analysis. GmLCL1 and GmLCL2 had
      similar circadian expression patterns and both were morning genes, while GmTOC1
      was an evening gene and peaked in the evening. The expressions of GmLCL1 and
      GmLCL2 were obviously antiphase to that of GmTOC1.Our study provided a system
      that simplified the experiments without compromising the quality of data obtained
      and was suitable for analyzing the molecular mechanism of flowering in soybean.
      GmLCL1, GmLCL2 and GmTOC1 may be the components of central clock in soybean.

PMID- 18707798
TI  - Nickel sorption capacity of ground xylem of Quercus ilex trees and effects of
      selected ligands present in the xylem sap.
AB  - In this work the influence of four different ligands present in the xylem sap of
      Quercus ilex (histidine, citric, oxalic and aspartic acids) on Ni(II) adsorption
      by xylem was investigated. Grinded xylem was trapped in acrylic columns and
      solutions of Ni(II), in the absence and presence of the four ligands prepared in
      KNO(3) 0.1molL(-1) at pH 5.5, were percolated through the column. Aliquots of
      solutions were recovered in the column end for Ni determination by graphite
      furnace atomic absorption spectrometry (GFAAS). The experimental data to describe
      Ni sorption by xylem in both the presence and absence of ligands was better
      explained by the Freundlich isotherm model. The decreasing affinity order of
      ligands for Ni was: oxalic acid>citric acid>histidine>aspartic acid. On the other
      hand, the Ni(II) adsorption by xylem increased following the inverse sequence of
      ligands. Potentiometric titrations of acidic groups were carried out to elucidate
      the sorption site groups available in Q. ilex xylem. The potentiometric titration
      has shown three sorption sites: pK(a) 2.6 (57.7% of the sorption sites), related
      to monobasic aliphatic carboxylic acids or nitrogen aromatic bases, pK(a) 8.1
      (9.6%) and pK(a) 9.9 (32.7%), related to phenolic groups.

PMID- 18707797
TI  - Transport functions and expression analysis of vacuolar membrane aquaporins in
      response to various stresses in rice.
AB  - The vacuole, a multifunctional organelle of most plant cells, has very important
      roles in space filling, osmotic adjustment, storage and digestion. Previous
      researches suggested that aquaporins in the tonoplast were involved in vacuolar
      functions. The rice genome contains 33 aquaporin genes, 10 of which encode
      tonoplast intrinsic proteins (TIPs). However, the function of each individual TIP
      isoform and the integrated function of TIPs under various physiological
      conditions remain elusive. Here, five rice TIP members were characterized with
      water and/or glycerol transport activities using the Xenopus oocyte expression
      system. OsTIP1;2, OsTIP2;2, OsTIP4;1 and OsTIP5;1 possessed water transport
      activity. OsTIP1;2, OsTIP3;2 and OsTIP4;1 were demonstrated with glycerol
      transport activity. Rice TIP expression patterns under various abiotic stress
      conditions including dehydration, high salinity, abscisic acid (ABA) and during
      seed germination were investigated by real-time PCR. OsTIP1s (OsTIP1;1 and
      OsTIP1;2) were highly expressed during seed germination, whereas OsTIP3s
      (OsTIP3;1 and OsTIP3;2) were specifically expressed in mature seeds with a
      decrease in expression levels upon germination. The results of this research
      provided a functional and expression profiles of rice TIPs.

PMID- 18707799
TI  - Topical methyl-aminolevulinate photodynamic therapy using red light-emitting
      diode light for treatment of multiple actinic keratoses: A randomized, double
      blind, placebo-controlled study.
AB  - BACKGROUND: The use of light-emitting diode light offers practical advantages in
      photodynamic therapy (PDT) with topical methyl-aminolevulinate (MAL) for
      management of actinic keratoses (AK). OBJECTIVE: We sought to evaluate the
      efficacy of MAL PDT using red light-emitting diode light. METHODS: We conducted a
      multicenter, double-blind, randomized study. A total of 49 patients with 363 AK
      lesions had 16.8% MAL cream applied under occlusion for 3 hours, and 47 patients
      with 360 AK lesions had vehicle cream similarly applied. The lesions were then
      illuminated (630 nm, light dose 37 J/cm2) with repeated treatment 1 week later.
      Complete lesion and patient (all lesions showing complete response) response
      rates were evaluated 3 months after last treatment. RESULTS: MAL PDT was superior
      (P<.0001) to vehicle PDT with respect to lesion complete response (86.2% vs
      52.2%, odds ratio 6.9 [95% confidence interval 4.7-10.3]) and patient complete
      response (59.2% vs 14.9%, odds ratio 13.2 [95% confidence interval 4.1-43.1]).
      LIMITATIONS: The study population may not be representative of all patients with
      AK. CONCLUSION: MAL PDT using red light-emitting diode light is an appropriate
      treatment alternative for multiple AK lesions.

PMID- 18707800
TI  - Mortality of bullous pemphigoid: an evaluation of 223 patients and comparison
      with the mortality in the general population in the United States.
AB  - BACKGROUND: There are large discrepancies in reported mortality for bullous
      pemphigoid (BP). OBJECTIVE: We sought to determine the mortality of a large
      cohort of patients with BP and compare this with age-matched control subjects.
      METHODS: Data were collected on 223 patients with a new diagnosis of BP between
      1998 and 2003 through our cutaneous immunofluorescence laboratory databases. The
      mortality of patients with BP was compared with that of age-matched control
      subjects in the general US population. RESULTS: The 1-, 2-, and 5-year mortality
      was 0.23 (95% confidence interval=0.18, 0.29), 0.37 (95% confidence
      interval=0.31, 0.44), and 0.50 (95% confidence interval=0.42, 0.57),
      respectively. However, relative to age-matched control subjects, no difference in
      expected mortality was detected. LIMITATIONS: This was a retrospective cohort
      analysis. CONCLUSIONS: Mortality of patients with BP is more likely related to
      advanced age and associated medical conditions than to disease-specific factors.

PMID- 18707801
TI  - L-stepholidine reduced L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of
      Parkinson's disease.
AB  - L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) remains a
      challenge in Parkinson's disease (PD) drug therapy. In the present study, we
      examined the effect of L-stepholidine (L-SPD), a known dual dopamine receptor
      agent, on LID in 6-hydroxydopamine (6-OHDA)-lesioned PD rat model. Daily
      administration of L-DOPA to PD rats for 22 days induced steady expression of LID,
      co-administration of L-SPD with L-DOPA significantly ameliorated LID without
      compromising the therapeutic potency of L-DOPA, indicating that L-SPD attenuated
      LID development. L-SPD alone elicited stable contralateral rotational behavior
      without inducing significant dyskinesia. Acute administration of L-SPD to rats
      with established LID produced significant relief of dyskinesia; this effect was
      mimicked by D(2) receptor antagonist haloperidol, but blunted by 5-HT(1A)
      receptor antagonist WAY100635. Furthermore, the mRNA level of 5-HT(1A) decreased
      significantly on 6-OHDA-lesioned striata, whereas chronic L-SPD treatment
      restored 5-HT(1A) receptor mRNA level on the lesioned striata. The present data
      demonstrated that L-SPD elicited antidyskinesia effects via both dopamine (D(2)
      receptor antagonistic activity) and nondopamine (5-HT(1A) agonistic activity)
      mechanisms.

PMID- 18707802
TI  - Subjectivity and the valid assessment of pre-registration student nurse clinical
      learning outcomes: implications for mentors.
AB  - This discussion, supported by the author's personal reflections as a mentor and
      teacher, examines the issue of subjectivity when assessing the competence of pre
      registration nursing students during their clinical placements. A difference is
      highlighted between valid and invalid subjectivity affecting the quality of
      mentors' assessments. Valid subjectivity refers to situations where students and
      mentors enter into a contract of trust and commitment from the outset of
      placement learning, enabling the 'substantiated' opinion of mentors to become a
      credible part of proficiency assessment. Invalid subjectivity presupposes that
      there has been limited investment in the student/mentor relationship and that
      assessment is therefore more reliant on the 'unconfirmed' views of mentors.
      Humanistic approaches to evaluating student learning are explored and a question
      is posed as to whether the trustworthiness of subjective assessment is improved
      when there is a sense of mutual reciprocity between students and mentors.
      Particular reference is made to reflective practice in adding meaning to this
      connection. Finally, an example of holistic assessment during 'live' clinical
      supervision involving a student and this author is offered (Table 1), in order to
      illustrate the implications for mentors attempting to enhance subjective
      evaluation of student learning.

PMID- 18707803
TI  - Deficits in executed and imagined aiming performance in brain-injured children.
AB  - Motor disorders are a frequent consequence of acquired brain injury (ABI) in
      children and much effort is currently invested in alleviating these deficits. The
      aim of the present study was to test motor imagery (MI) capabilities in children
      with ABI (n=25) and an age- and gender-matched control group (n=25). A
      computerized Virtual Radial Fitts Task (VRFT) was used to investigate the speed
      accuracy trade-offs (or Fitts' law) that occur as target size is varied for both
      executed and imagined performance. In the control group, the speed for accuracy
      trade-off for both executed and imagined performance conformed to Fitts' law. In
      the ABI group, only executed movements conformed to Fitts' law. These findings
      suggest that children with ABI show an inferior ability to imagine the time
      needed to complete goal-directed movements with differential difficulty levels.

PMID- 18707804
TI  - Open to debate. The motion: perioperative chemotherapy in muscle invasive bladder
      cancer improves survival.

PMID- 18707805
TI  - Re: Fleur I. de Korte, Jochem W. van Werkum, Peter L.M. Vijverberg, Jurrien M.
      ten Berg. Late coronary stent thrombosis complicating urologic surgery. Eur Urol
      2008;54:221-5.

PMID- 18707806
TI  - Should we perform imaging-guided lymph node dissection in patients with lymphatic
      recurrence of prostate cancer after radical prostatectomy?

PMID- 18707807
TI  - Beyond prone position in percutaneous nephrolithotomy: a comprehensive review.
AB  - CONTEXT: Percutaneous nephrolithotomy (PNL) is traditionally performed with the
      patient in the prone position. OBJECTIVE: To assess the efficacy and safety of
      the prone and supine positions, particularly in obese patients and in those with
      staghorn calculi. EVIDENCE ACQUISITION: A Medline search was conducted for
      articles published during the last 10 yr related to PNL in the prone and supine
      positions. EVIDENCE SYNTHESIS: This search revealed 9 published studies for
      supine and 25 for prone PNL. None of the supine PNL studies reported visceral
      injuries, while transfusion rates were 0.0-9.4% and stone-free rates were 69.6
      95.0%. One study of supine PNL evaluated a significant proportion of obese
      patients. Prone PNL studies in obese patients report transfusion rates of 3.2
      8.8% and stone-free rates of 79.0-89.2%. In the only randomized study, excluding
      obese patients and staghorn calculi, operative time favors the supine position. A
      nonrandomized comparative study demonstrated similar complication rates with
      insignificant improvement in treatment success for supine PNL; however, when
      comparing series with similar proportions of staghorn calculi cases, there are
      slightly improved outcomes for prone PNL. Moreover, comparison of weighted means
      favors prone PNL. CONCLUSIONS: For obese patients and staghorn calculi, prone PNL
      appears to be associated with decreased operative times with similar bleeding
      rates and slightly better stone-free rates than supine PNL.

PMID- 18707808
TI  - Release of cell-free DNA into the bloodstream leads to high levels of non-tumor
      plasma DNA during tumor progression in rats.
AB  - To examine the implications of cell-free DNA in the plasma in neoplastic disease,
      it is necessary to clarify various features of this DNA, such as the contribution
      of DNA from the host's normal cells and the kinetics of the release of this
      latter DNA. To quantify non-tumor DNA in the plasma of tumor-bearing rats and to
      correlate levels of this DNA with tumor progression, we injected DHD/K12-PROb
      colon cancer cells subcutaneously into BD-IX rats and recorded tumor diameters
      weekly. After euthanasia, we collected plasma from each rat and quantified non
      mutated and mutated DNA in the plasma. Overall, levels of non-mutated (non-tumor)
      DNA in plasma of tumor-bearing animals were significantly higher than those in
      healthy animals measured by real-time PCR (p=0.001). However, 5 weeks after
      inoculation, levels were similar to those in healthy animals. As a whole, levels
      of non-mutated DNA were not significantly related to tumor size or to metastasis.
      However, when we excluded animals that were analyzed earliest, we found a
      positive and statistically significant correlation between levels of non-mutated
      DNA and tumor diameter (p=0.002). Release of cell-free DNA into the plasma during
      tumor progression appears to follow a predictable time course in a homogeneous
      population. In addition, large amounts of non-tumor DNA are released during tumor
      progression and, in particular, at early stages. Our findings support the
      hypothesis that interactions between tumor cells and host cells result in release
      of cell-free DNA.

PMID- 18707809
TI  - Experimental quantification of annular dark-field images in scanning transmission
      electron microscopy.
AB  - This paper reports on a method to obtain atomic resolution Z-contrast (high-angle
      annular dark-field) images with intensities normalized to the incident beam. The
      procedure bypasses the built-in signal processing hardware of the microscope to
      obtain the large dynamic range necessary for consecutive measurements of the
      incident beam and the intensities in the Z-contrast image. The method is also
      used to characterize the response of the annular dark-field detector output,
      including conditions that avoid saturation and result in a linear relationship
      between the electron flux reaching the detector and its output. We also
      characterize the uniformity of the detector response across its entire area and
      determine its size and shape, which are needed as input for image simulations. We
      present normalized intensity images of a SrTiO(3) single crystal as a function of
      thickness. Averaged, normalized atom column intensities and the background
      intensity are extracted from these images. The results from the approach
      developed here can be used for direct, quantitative comparisons with image
      simulations without any need for scaling.

PMID- 18707810
TI  - Parasites of sheep and goats and their prevalence in Bokova, a rural area of Buea
      Sub Division, Cameroon.
AB  - Small ruminant production in the South West Province of Cameroon is practised
      mostly by subsistence farmers in the rural areas on natural grass pastures which
      grow once the primary forest has been cleared. Investigations revealed certain
      endo- and ectoparasites that were abundant and caused problems on the pastures to
      both animals and farmers. Haemonchus contortus was the most prevalent species
      with a prevalence of 94.23%. The highest mean monthly intensity was obtained in
      August and there was a significant difference (P<0.05) from the other months.
      Strongyle infections were prevalent in 93.18% of the animals examined. In the
      flock there was a prevalence of 96.25% in sheep as opposed to 86% in goats. The
      prevalence in the subsistence system was 95.4%. Mean monthly egg counts and
      prevalence of flukes was highest in December, 187.84 (29.73%). The overall
      prevalence of flukes was 73.88% with an overall mean intensity of 22 flukes per
      animal. The most abundant tick species was Haemaphysilis leachi. Genital
      distribution of ticks was significantly higher (P<0.05) in females than males. In
      the males they were more concentrated around the scrotum.

PMID- 18707811
TI  - Prevalence of Toxoplasma gondii infection in Belgian house cats.
AB  - Five hundred and sixty seven sera of healthy house cats aged 3 months to 7 years,
      were examined for the presence of anti-toxoplasma antibodies by indirect
      immunofluorescence assay and compared to SAG1 and TLA enzyme linked immunosorbent
      assays as alternative test. Twenty-five percent of cats tested positive for IgG
      and/or IgM. Seroprevalence increased with age from 2% below 12 months of age up
      to 44% at age 7. Sensitivities of SAG1 and TLA ELISA were 84.1% and 88.6%,
      respectively. Peak levels in seroprevalence were correlated to increased IgG
      titers in TLA ELISA. Our results suggest that T. gondii infections are common in
      house cats and that there is a high chance for a negative cat to seroconvert in
      its second life-year.

PMID- 18707813
TI  - Exercise interval training: an improved stimulus for improving the physiology of
      pre-diabetes.
AB  - Current reports estimate that type II diabetes (T2D) affects 5-8% of adults. Also
      recognized is a transitional group of patients whose fasting blood glucose is
      abnormal; yet, not considered high enough to be diagnosed as diabetes. Defined as
      "pre-diabetes" these individuals have impaired fasting glucose (IFG; fasting
      glucose 100-125 mg/dL), impaired glucose tolerance (IGT; 2 h glucose 140-199
      mg/dL) or both. Two unifying features associated with IFG and IGT are their
      strong links to obesity and physical inactivity, which lead independently and
      collectively toward the erosion of various cellular processes affecting glucose
      control. In contrast, regular exercise positively influences IFG/IGT and obesity,
      thus representing an important therapy for preventing diabetes via the
      enhancement of several mechanisms of action. These include improved glucose
      metabolism, muscle respiratory capacity, mitochondrial respiratory chain activity
      and beta-oxidation. Contemporary exercise guidelines provided by various
      organizations recommend that exercise be performed at intensities ranging from
      40% to 85% of maximal aerobic capacity. Unfortunately, little is known regarding
      the optimal intensity to best facilitate the physiological benefits associated
      with exercise. An evolving body of research shows that interval training produces
      greater changes in exercise capacity than traditional aerobic training. Interval
      training involves bouts of high exercise intensity (15s to 4 min; >90% VO(2max))
      followed by a recovery period (40-50% VO(2max)) of equal or longer duration than
      the associated work interval. Though the net effect of interval training is
      aerobic, periodic excursions involving anaerobic energy pathways theoretically
      "push" the mitochondria to greater improvements in exercise capacity,
      mitochondrial biogenesis, enzymatic markers associated with glycolysis, aerobic
      metabolism and beta (beta)-oxidation. Though traditionally viewed as a training
      modality for athletes, a recent report has demonstrated that interval training is
      more effective than traditional aerobic exercise training in patients up to
      approximately 75 y of age and with low functional capacities (VO(2max) 13
      ml/kg/min) by producing superior improvements in VO(2max), sub-maximal exercise
      tolerance, levels of peroxisome proliferator activator protein-gamma co
      activator1alpha (PGC-1alpha), and quality of life indices more so than
      traditional aerobic exercise training. Erosion in these same markers is present
      in populations with pre-diabetes and T2D. The principal hypothesis of this paper
      is that interval training will provide a more powerful stimulus for improving
      insulin sensitivity than traditional low-to-moderate intensity aerobic
      conditioning. This theory further proposes that these affects will be due to
      greater changes in specific metabolic pathways associated with glycolysis,
      aerobic metabolism, beta-oxidation, and mitochondrial biogenesis.

PMID- 18707812
TI  - Decreased brain docosahexaenoic acid content produces neurobiological effects
      associated with depression: Interactions with reproductive status in female rats.
AB  - Decreased tissue levels of docosahexaenoic acid (DHA; 22:6n-3) are implicated in
      the etiologies of non-puerperal and postpartum depression. With the aim of
      determining neurobiological sequelae of decreased brain DHA content, this study
      examined the effects of a loss of brain DHA content and concurrent reproductive
      status in adult female Long-Evans rats. An alpha-linolenic acid-deficient diet
      and breeding protocols were used to produce virgin and parous female rats with
      cortical phospholipid DHA levels 23-26% lower than virgin and parous rats fed a
      control diet containing adequate alpha-linolenic acid. Parous dams were
      tested/euthanized at weaning (postnatal day 20) of the second litter; virgin
      females, during diestrus. Decreased brain DHA was associated with decreased
      hippocampal BDNF gene expression and increased relative corticosterone response
      to an intense stressor, regardless of reproductive status. In virgin females with
      decreased brain DHA, serotonin content and turnover in frontal cortex were
      decreased compared to virgin females with normal brain DHA. In parous dams with
      decreased brain DHA, the density of 5-HT(1A) receptors in the hippocampus was
      increased, corticosterone response to an intense stressor was increased, and the
      latency to immobility in the forced swim test was decreased compared to parous
      dams with normal DHA. These findings demonstrate neurobiological alterations
      attributable to decreased brain DHA or an interaction of parous status and brain
      DHA level. Furthermore, the data are consistent with findings in depressed
      humans, and thus support a role for DHA as a factor in the etiologies of
      depressive illnesses, particularly postpartum depression.

PMID- 18707814
TI  - Restoring the metabolic disturbance of zinc: may not only contribute to the
      prevention of esophageal squamous cell cancer.
AB  - The relationship between zinc deficiency (ZD) and esophageal squamous cell cancer
      (ESCC) is well-established. Zinc supplement has long been considered as potential
      strategy for prevention of ESCC. However, the effect of zinc replenishment on
      prevention of ESCC is still in controversy and no convincing evidence to support
      these proposals has become known. We hypothesized that zinc deficiency might be
      the major initiator for dysfunction of numerous genes and subsequent
      carcinogenesis of esophagus, and replenishment of zinc might improve the
      prognosis of patients with ESCC.

PMID- 18707815
TI  - A novel strategy for prefabrication of large and axially vascularized tissue
      engineered bone by using an arteriovenous loop.
AB  - The repair of bone defects remains a major clinical challenge because none
      available reconstruction methods and biomaterials have been proved completely
      satisfactory. As a promising approach for bone regeneration, tissue engineered
      bone has become a technically feasible method to repair small to moderate sized
      bone defects in clinical practice, but it is difficult to repair large one,
      particularly when the recipient site is scarred by infection or radiation injury.
      Construction of large and vascularized tissue engineered bone may overcome the
      problems since vascularization is an essential prerequisite for the constructs to
      survive and integrate with existing host tissue. On the other hand,
      prefabrication large artificial bone in vivo bioreactor and axial vascularization
      by means of arteriovenous loop model in soft tissue have been proved to be
      feasible. Therefore, we hypothesize that combination of cells, solid scaffold,
      growth factors, and arteriovenous loop may eventually generate a large and
      vascularized tissue engineered bone flap in vivo bioreactor. Like vascularized
      autologous bone grafts, the new constructs could be transferred to the defect
      site by using microsurgical techniques. The strategy would facilitate clinical
      translation in bone tissue engineering and offer new therapeutic strategies for
      reconstruction of extended bone defects if the hypothesis proved to be practical.

PMID- 18707816
TI  - NFkappaB gene silencing inhibits wear particles-induced inflammatory osteolysis.
AB  - Wear particles-induced periprosthetic osteolysis involved in proinflammatory
      cytokine production and osteoclastogenesis, is the major cause of prosthetic join
      implant loosening. Recent advances in our understanding of cellular and molecular
      mechanisms of periprosthetic osteolysis have highlighted cytokine release and
      osteoclast function controlled by numerous intracellular signaling pathway, one
      of which is nuclear factor kappa B (NFkappaB). Direct inhibition of NFkappaB is
      an efficient therapy to block bone erosion associated with inflammatory
      arthritis. There are no approved nonoperative treatments for periprosthetic
      osteolysis. Gene therapy, however, offers novel possibilities. As the implant
      interface cells are located in the closed joint space, intra-articular injection
      of siRNA (small interfering RNA) is accessible as local administration to avoid
      systemic side effect. We postulate that local administration of siRNA for
      NFkappaB could inhibit wear particles-induced inflammatory osteolysis. In our
      opinion, this gene therapy seems to hold interesting future prospects for
      effective therapeutic interventions in humans.

PMID- 18707817
TI  - A matched-pair analysis comparing whole-brain radiotherapy plus stereotactic
      radiosurgery versus surgery plus whole-brain radiotherapy and a boost to the
      metastatic site for one or two brain metastases.
AB  - PURPOSE: To compare the results of whole-brain radiotherapy plus stereotactic
      radiosurgery (WBRT+SRS) with those of surgery plus whole-brain radiotherapy and a
      boost to the metastatic site (OP+WBRT+boost) for patients with one or two brain
      metastases. METHODS AND MATERIALS: Survival, intracerebral control, and local
      control of the treated metastases were retrospectively evaluated. To reduce the
      risk of selection bias, a matched-pair analysis was performed. The outcomes of 47
      patients who received WBRT+SRS were compared with those of a second cohort of 47
      patients who recieved OP+WBRT+boost. The two treatment groups were matched for
      the following potential prognostic factors: WBRT schedule, age, gender,
      performance status, tumor type, number of brain metastases, extracerebral
      metastases, recursive partitioning analysis class, and interval from tumor
      diagnosis to WBRT. RESULTS: The 1-year survival rates were 65% after WBRT+SRS and
      63% after OP+WBRT+boost (p = 0.19). The 1-year intracerebral control rates were
      70% and 78% (p = 0.39), respectively. The 1-year local control rates were 84% and
      83% (p = 0.87), respectively. On multivariate analyses, improved survival was
      significantly associated with better performance status (p = 0.009), no
      extracerebral metastases (p = 0.004), recursive partitioning analysis Class 1 (p
      = 0.004), and interval from tumor diagnosis to WBRT (p = 0.001). Intracerebral
      control was not significantly associated with any of the potential prognostic
      factors. Improved local control was significantly associated with no
      extracerebral metastases (p = 0.037). CONCLUSIONS: Treatment outcomes were not
      significantly different after WBRT+SRS compared with OP+WBRT+boost. However,
      WBRT+SRS is less invasive than OP+WBRT+boost and may be preferable for patients
      with one or two brain metastases. The results should be confirmed by randomized
      trials.

PMID- 18707818
TI  - Prospective assessment of gastrointestinal and genitourinary toxicity of salvage
      radiotherapy for patients with prostate-specific antigen relapse or local
      recurrence after radical prostatectomy.
AB  - PURPOSE: To assess the acute and late gastrointestinal (GI) and genitourinary
      (GU) toxicity of salvage radiotherapy (RT). METHODS AND MATERIALS: A total of 75
      patients with prostate-specific antigen relapse or clinically isolated local
      recurrence after radical prostatectomy were accrued between 1998 and 2002 for a
      Phase II study to evaluate the efficacy of salvage RT plus 2-year androgen
      suppression. Acute and late GI and GU toxicity was prospectively assessed using
      the National Cancer Institute Expanded Common Toxicity Criteria Version 2. For
      acute toxicity, prevalence was examined. For late toxicity, cumulative incidences
      of Grade 2 or higher and Grade 3 toxicity were calculated. RESULTS: Median age
      was 67 years at the time of salvage RT. Median time from radical prostatectomy to
      RT was 36.2 months. Median follow-up was 45.1 months. Seventy-five patients were
      available for acute toxicity analysis, and 72 for late toxicity. Twelve percent
      and 40% had preexisting GI and GU dysfunction before RT, respectively. Sixty
      eight percent, 21%, and 5% experienced Grade 1, 2, and 3 acute GI or GU toxicity,
      respectively. Cumulative incidences of Grade 2 or higher late GI and GU toxicity
      at 36 months were 8.7% and 22.6%, and Grade 3 late GI and GU toxicity, 1.6% and
      2.8%, respectively. None had Grade 4 late toxicity. The severity of acute GU
      toxicity (Grade < 2 vs. >/= 2) was a significant predictor factor for Grade 2 or
      higher late GU toxicity after adjusting for preexisting GU dysfunction.
      CONCLUSION: Salvage RT generally was well tolerated. Grade 3 or higher late GI or
      GU toxicity was uncommon.

PMID- 18707819
TI  - Relative contributions of radiation and cisplatin-based chemotherapy to
      sensorineural hearing loss in head-and-neck cancer patients.
AB  - PURPOSE: To investigate the risk of sensorineural hearing loss (SNHL) in patients
      with head-and-neck cancer and treated with radiation therapy (RT) or concomitant
      cisplatin-based chemoradiation, the relationship among SNHL and radiation dose to
      the cochlea, the use of two common cisplatin dose regimens. METHODS AND
      MATERIALS: A total of 62 head-and-neck cancer patients treated with curative
      intent were included in this prospective study. Of the patients, 21 received RT
      alone, 27 received 40 mg/m(2) weekly cisplatin, 13 received 100 mg/m(2) every 3
      weeks during RT, and 1 received RT with weekly epidermal growth factor receptor
      inhibitor antibody. The effect of chemotherapy and RT dose on hearing was
      determined using a model that accounted for the age and variability between each
      ear for each patient. RESULTS: We constructed a model to predict dose-dependent
      hearing loss for RT or cisplatin-based chemotherapy either alone or in
      combination. For patients only receiving RT, no significant hearing loss was
      found at doses to the cochlea of less than 40 Gy. Patients receiving 100 mg/m(2)
      or 40 mg/m(2) of cisplatin chemotherapy had an estimated +21.5 dB and +9.5 dB
      hearing loss at 8,000 Hz with low radiation doses (10 Gy), which rose to +38.4 dB
      and +18.9 dB for high radiation doses (40 Gy). CONCLUSIONS: Use of RT alone with
      doses of less than 40 Gy did not result in clinically significant hearing loss.
      High-frequency SNHL was profoundly damaged in patients who received concomitant
      cisplatin when doses of 100 mg/m(2) were used. The threshold cochlear dose for
      hearing loss with cisplatin-based chemotherapy and RT was predicted to be 10 Gy.
      The inner ear radiation dose constraints and cisplatin dose intensity should be
      considered in the treatment of advanced head-and-neck cancer.

PMID- 18707820
TI  - Weekly carboplatin reduces toxicity during synchronous chemoradiotherapy for
      Merkel cell carcinoma of skin.
AB  - PURPOSE: The toxicity of radiotherapy (RT) combined with weekly carboplatin and
      adjuvant carboplatin and etoposide was prospectively assessed in a group of
      patients with high-risk Stage I and II Merkel cell carcinoma of the skin. This
      regimen was compared with the Trans-Tasman Radiation Oncology Group 96:07 study,
      which used identical eligibility criteria but carboplatin and etoposide every 3
      weeks during RT. PATIENTS AND METHODS: Patients were eligible if they had disease
      localized to the primary site and lymph nodes, with high-risk features. RT was
      delivered to the primary site and lymph nodes to a dose of 50 Gy and weekly
      carboplatin (area under the curve of 2) was given during RT. This was followed by
      three cycles of carboplatin and etoposide. A total of 18 patients were entered
      into the study, and their data were compared with the data from 53 patients
      entered into the Trans-Tasman Radiation Oncology Group 96:07 study. RESULTS:
      Involved lymph nodes (Stage II) were present in 14 patients (77%). Treatment was
      completed as planned in 16 patients. The weekly carboplatin dose was delivered in
      17 patients, and 15 were able to complete all three cycles of adjuvant
      carboplatin and etoposide. Grade 3 and 4 neutrophil toxicity occurred in 7
      patients, but no cases of febrile neutropenia developed. Compared with the Trans
      Tasman Radiation Oncology Group 96:07 protocol (19 of 53 cases of febrile
      neutropenia), the reduction in the febrile neutropenia rate (p = 0.003) and
      decrease in Grade 3 skin toxicity (p = 0.006) were highly statistically
      significant. CONCLUSION: The results of our study have shown that weekly
      carboplatin at this dosage is a safe way to deliver synchronous chemotherapy
      during RT for MCC and results in a marked reduction of febrile neutropenia and
      Grade 3 skin toxicity compared with the three weekly regimen.

PMID- 18707821
TI  - Final report of multicenter Canadian Phase III randomized trial of 3 versus 8
      months of neoadjuvant androgen deprivation therapy before conventional-dose
      radiotherapy for clinically localized prostate cancer.
AB  - PURPOSE: To evaluate the effect of 3 vs. 8 months of neoadjuvant hormonal therapy
      before conventional-dose radiotherapy (RT) on disease-free survival for localized
      prostate cancer. METHODS AND MATERIALS: Between February 1995 and June 2001, 378
      men were randomized to either 3 or 8 months of flutamide and goserelin before 66
      Gy RT at four participating centers. The median baseline prostate-specific
      antigen level was 9.7 ng/mL (range, 1.3-189). Of the 378 men, 26% had low-, 43%
      intermediate-, and 31% high-risk disease. The two arms were balanced in terms of
      age, Gleason score, clinical T category, risk group, and presenting prostate
      specific antigen level. The median follow-up for living patients was 6.6 years
      (range, 1.6-10.1). Of the 378 patients, 361 were evaluable, and 290 were still
      living. RESULTS: The 5-year actuarial freedom from failure rate for the 3- vs. 8
      month arms was 72% vs. 75%, respectively (p = 0.18). No difference was found in
      the failure types between the two arms. The median prostate-specific antigen
      level at the last follow-up visit for patients without treatment failure was 0.6
      ng/mL in the 3-month arm vs. 0.50 ng/mL in the 8-month arm. The disease-free
      survival rate at 5 years was improved for the high-risk patients in the 8-month
      arm (71% vs. 42%, p = 0.01). CONCLUSION: A longer period of NHT before standard
      dose RT did not alter the patterns of failure when combined with 66-Gy RT. High
      risk patients in the 8-month arm had significant improvement in the 5-year
      disease-free survival rate.

PMID- 18707822
TI  - Ten-year recurrence rates in young women with breast cancer by locoregional
      treatment approach.
AB  - PURPOSE: Young women with breast cancer have higher locoregional recurrence (LRR)
      rates than older patients. The goal of this study is to determine the impact of
      locoregional treatment strategy, breast-conserving therapy (BCT), mastectomy
      alone (M), or mastectomy with adjuvant radiation (MXRT), on LRR for patients 35
      years or younger. METHODS AND MATERIALS: Data for 668 breast cancers in 652 young
      patients with breast cancer were retrospectively reviewed; 197 patients were
      treated with BCT, 237 with M, and 234 with MXRT. RESULTS: Median follow-up for
      all living patients was 114 months. In the entire cohort, 10-year actuarial LRR
      rates varied by locoregional treatment: 19.8% for BCT, 24.1% for M, and 15.1% for
      MXRT (p = 0.05). In patients with Stage II disease, 10-year actuarial LRR rates
      by locoregional treatment strategy were 17.7% for BCT, 22.8% for M, and 5.7% for
      MXRT (p = 0.02). On multivariate analysis, M (hazard ratio, 4.45) and Grade III
      disease (hazard ratio, 2.24) predicted for increased LRR. In patients with Stage
      I disease, there was no difference in LRR rates based on locoregional treatment
      (18.0% for BCT, 19.8% for M; p = 0.56), but chemotherapy use had a statistically
      significant LRR benefit (13.5% for chemotherapy, 27.9% for none; p = 0.04).
      CONCLUSIONS: Young women have high rates of LRR after breast cancer treatment.
      For patients with Stage II disease, the best locoregional control rates were
      achieved with MXRT. For patients with Stage I disease, similar outcomes were
      achieved with BCT and mastectomy; however, chemotherapy provided a significant
      benefit to either approach.

PMID- 18707823
TI  - Impact of adding concomitant chemotherapy to hyperfractionated accelerated
      radiotherapy for advanced head-and-neck squamous cell carcinoma.
AB  - PURPOSE: To evaluate the feasibility and efficacy of a hyperfractionated
      accelerated radiotherapy (RT) schedule combined with concomitant chemotherapy
      (Cx) in patients with locally advanced head-and-neck squamous cell carcinoma.
      METHODS AND MATERIALS: Between 2004 and 2007, a total of 90 patients with
      locoregionally advanced head-and-neck squamous cell carcinoma underwent
      irradiation according to a hybrid fractionation schedule consisting of 20
      fractions of 2 Gy (once daily) followed by 20 fractions of 1.6 Gy (twice daily)
      to a total dose of 72 Gy. Concomitant Cx (cisplatinum 100 mg/m(2)) was
      administered at the start of Weeks 1 and 4. Treatment outcome and toxicity were
      retrospectively compared with a previous patient group (n = 73) treated with the
      same schedule, but without concomitant Cx, between 2001 and 2004. RESULTS: The
      locoregional control (LRC) rate was 70% after 2 years. Two-year overall and 2
      year disease-free survival rates were 74% and 60%, respectively. In comparison
      with the RT-only group, an improvement of 15% in both LRC (p = 0.03) and overall
      survival (p = 0.09) was observed. All patients were treated to full radiation
      dose according to protocol, although the Cx schedule had to be adjusted in 12
      patients. No acute Grade 4 or 5 toxicity was seen, but incidences of Grade 3
      acute mucositis (74.5% vs. 50.7%; p = 0.002) and dysphagia (82.2% vs. 47.9%; p <
      0.001) were significantly higher in the chemoradiotherapy group compared with
      patients treated with RT alone. CONCLUSION: With this chemoradiotherapy regimen,
      excellent LRC and survival rates were achieved, with acceptable acute toxicity.

PMID- 18707824
TI  - Effectiveness and morbidity associated with reirradiation in conservative salvage
      management of recurrent soft-tissue sarcoma.
AB  - PURPOSE: The management of isolated local recurrence of soft-tissue sarcoma is
      therapeutically complex, and functional conservative management is preferable to
      radical or amputative salvage surgery. This study reviews the University of
      Florida experience using conservative resection and reirradiation to manage
      isolated local recurrences of soft-tissue sarcoma. METHODS AND MATERIALS: Between
      1976 and 2005, a total of 14 patients who underwent primary conservative
      resection and irradiation developed isolated local recurrence and were managed
      with salvage conservative resection and reirradiation. Of the patients treated, 3
      had tumors of the distal extremity, 8 had tumors of the proximal extremity, and 3
      had tumors of the trunk. At the time of recurrence, 64% of tumors were greater
      than 5 cm and 79% were high grade. In combination with gross total resection, 13
      of 14 patients received external beam radiotherapy with or without brachytherapy,
      and 1 patient was treated with brachytherapy alone. Two patients received
      chemotherapy. RESULTS: The median follow-up was 30 months, and no living patients
      were lost during follow-up. From retreatment, the 5-year actuarial overall
      survival, cause-specific survival, and local control rates were 40%, 40%, and 18%
      respectively. There was a 50% incidence of serious complication requiring either
      reoperation or leading to permanent functional impairment. Of the 14 patients,
      only 1 has remained disease free and without significant complications. No
      treatment factors, including achieving wide surgical margins or delivering higher
      radiation dosages, seemed to confer an advantage in local control. CONCLUSIONS:
      Salvage therapy for management of locally recurrent soft-tissue sarcoma is
      challenging, and the effects of reoperation and reirradiation can be severe.

PMID- 18707825
TI  - Patterns of care for lung cancer in radiation oncology departments of Turkey.
AB  - PURPOSE: To determine the patterns of care for lung cancer in Turkish radiation
      oncology centers. METHODS AND MATERIALS: Questionnaire forms from 21 of 24
      (87.5%) centers that responded were evaluated. RESULTS: The most frequent
      histology was non-small cell lung cancer (NSCLC) (81%). The most common
      postoperative radiotherapy (RT) indications were close/(+) surgical margins (95%)
      and presence of pN2 disease (91%). The most common indications for postoperative
      chemotherapy (CHT) were ">/= IB" disease (19%) and the presence of pN2 disease
      (19%). In Stage IIIA potentially resectable NSCLC, the most frequent treatment
      approach was neoadjuvant concomitant chemoradiotherapy (CHRT) (57%). In Stage
      IIIA unresectable and Stage IIIB disease, the most frequent approach was
      definitive concomitant CHRT (91%). In limited SCLC, the most common treatment
      approach was concomitant CHRT with cisplatin+etoposide for cycles 1-3, completion
      of CHT to cycles 4-6, and finally prophylactic cranial irradiation in patients
      with complete response (71%). Six cycles of cisplatin + etoposide CHT and
      palliative thoracic RT, when required, was the most commonly used treatment (81%)
      in extensive SCLC. Sixty-two percent of centers did not have endobronchial
      brachytherapy (EBB) facilities. CONCLUSION: There is great variation in
      diagnostic testing, treatment strategies, indications for postoperative RT and
      CHT, RT features, and EBB availability for LC cases. To establish standards,
      national guidelines should be prepared using a multidisciplinary approach.

PMID- 18707826
TI  - Radiotherapy for extramedullary plasmacytoma of the head and neck.
AB  - PURPOSE: To define the effectiveness of radiotherapy in the treatment of patients
      with extramedullary plasmacytoma of the head and neck (EMPHN). METHODS AND
      MATERIALS: We searched the Mayo Clinic Rochester Department of Radiation Oncology
      electronic Tumor Registry and identified 18 consecutive patients with a diagnosis
      of solitary EMPHN. Sixteen patients were treated with radiotherapy at initial
      diagnosis and 2 received salvage radiotherapy for local failure after surgery.
      Median dose administered was 50.4 Gy. Median follow-up was 6.8 years. RESULTS:
      One patient (6%) developed a marginal recurrence 12 months after treatment. Six
      patients (33%) developed multiple myeloma (2 patients) or plasmacytomas at
      distant sites (4 patients) at a median of 3.1 years after diagnosis (range, 0.02
      to 9.6 years). Median and 5- and 10-year overall survival rates from the date of
      diagnosis are 12.5 years, 88%, and 55%, respectively. Two patients (11%)
      developed a radiation-induced malignancy at 6.5 and 6.9 years after treatment.
      CONCLUSIONS: Radiotherapy provides excellent local and regional tumor control and
      survival in patients with EMPHN. To the best of our knowledge, this is the first
      report of presumed radiation-induced malignancy in this patient population.

PMID- 18707827
TI  - Intensity-modulated radiotherapy in postoperative treatment of oral cavity
      cancers.
AB  - PURPOSE: To present our single-institution experience of intensity-modulated
      radiotherapy (IMRT) for oral cavity cancer. METHODS AND MATERIALS: Between
      September 2000 and December 2006, 35 patients with histologically confirmed
      squamous cell carcinoma of the oral cavity underwent surgery followed by
      postoperative IMRT. The sites included were buccal mucosa in 8, oral tongue in
      11, floor of the mouth in 9, gingiva in 4, hard palate in 2, and retromolar
      trigone in 1. Most patients had Stage III-IV disease (80%). Ten patients (29%)
      also received concurrent postoperative chemotherapy with IMRT. The median
      prescribed radiation dose was 60 Gy. RESULTS: The median follow-up for surviving
      patients was 28.1 months (range, 11.9-85.1). Treatment failure occurred in 11
      cases as follows: local in 4, regional in 2, and distant metastases in 5. Of the
      5 patients with distant metastases, 2 presented with dermal metastases. The 2-
      and 3-year estimates of locoregional progression-free survival, distant
      metastasis-free survival, disease-free survival, and overall survival were 84%
      and 77%, 85% and 85%, 70% and 64%, and 74% and 74%, respectively. Acute Grade 2
      or greater dermatitis, mucositis, and esophageal reactions were experienced by
      54%, 66%, and 40% of the patients, respectively. Documented late complications
      included trismus (17%) and osteoradionecrosis (5%). CONCLUSION: IMRT as an
      adjuvant treatment after surgical resection for oral cavity tumors is feasible
      and effective, with promising results and acceptable toxicity.

PMID- 18707828
TI  - Truths and myths about radiotherapy for verrucous carcinoma of larynx.
AB  - PURPOSE: The role of primary radiotherapy (RT) for laryngeal verrucous carcinoma
      (LVC) is controversial because of concerns about anaplastic transformation, an
      increased incidence of metastases, and poorer local control after RT. To address
      these concerns, we report our experience. METHODS AND MATERIALS: All patients
      with pathologically diagnosed LVC treated with primary RT at our institution
      between 1961 and 2004 were reviewed. The local control, overall survival, and
      disease-specific survival rate were established. The outcome after salvage
      treatment and the incidence of metastases and anaplastic transformation were
      determined. RESULTS: Of 62 LVC patients with a minimal follow-up of 2 years, 20
      local and 1 nodal recurrence were identified. Salvage surgery was undertaken in
      18 of the 21 patients, and disease control was achieved in 17; the eighteenth
      patient died of a complication after surgery. Ultimate laryngeal preservation was
      achieved in 50 patients (81%), including 42 after initial RT and an additional 8
      after salvage surgery. Distant failure and anaplastic transformation were not
      observed. Second cancers after RT were identified in 4 patients, only 1 of which
      was a head-and-neck cancer detected 11 years later. Of the 39 deceased patients,
      only 3 died of LVC. The local control, overall survival, and disease-specific
      survival rate at 5 years was 66% (95% confidence interval, 52-77%), 87% (95%
      confidence interval, 75-93%), and 97% (95% confidence interval, 87-99%),
      respectively. CONCLUSION: The results of our study have shown that the initial
      control of LVC with RT is less reliable compared with reports from surgical
      series; however, local recurrence was almost always salvaged successfully,
      resulting in disease-specific survival rates equivalent to those of surgical
      series. Neither anaplastic transformation nor unusual metastasis development was
      observed in this series.

PMID- 18707829
TI  - Obesity and risk of biochemical failure for patients receiving salvage
      radiotherapy after prostatectomy.
AB  - PURPOSE: Obesity has been proposed as an independent risk factor for patients
      undergoing surgery or radiotherapy (RT) for prostate cancer. Using body mass
      index (BMI) as a measure of obesity, we tested its role as a risk factor for
      patients receiving salvage RT after prostatectomy. METHODS AND MATERIALS: Rates
      of subsequent biochemical relapse were examined in 90 patients who underwent
      salvage RT between 1984 and 2004 for biochemical failure after radical
      prostatectomy. Median follow-up was 3.7 years. The BMI was tested as a continuous
      and categorical variable (stratified as <25, 25-<30, and >or=30 kg/m(2)).
      Univariate and multivariate proportional hazards regression analyses were
      performed for clinical, pathologic, and treatment factors associated with time to
      relapse after salvage RT. RESULTS: There were 40 biochemical failures after
      salvage RT with a median time to failure of 1.2 years. The BMI was not associated
      with adverse clinical, pathologic, or treatment factors. On multivariate
      analysis, obesity was independently significant (hazard ratio [HR], 1.2; p =
      0.01), along with RT dose (HR, 0.7; p = 0.003) and pre-RT prostate-specific
      antigen level (HR, 1.2; p = 0.0003). CONCLUSIONS: This study is weakly suggestive
      that obesity may be a risk factor for salvage RT patients. Whether this results
      from greater biologic aggressiveness or technical inadequacies cannot be answered
      by this study. Given the very high failure rate observed for severely obese
      patients, we propose that technical difficulties with RT are at play. This
      hypothesis is supported by the RT literature and could be prospectively
      investigated. Techniques that optimize targeting, especially in obese patients,
      perhaps seem warranted at this time.

PMID- 18707830
TI  - Thermoresistance sperm tests are not predictive of potential fertility for
      cryopreserved bull semen.
AB  - Different studies demonstrate positive correlations between seminal variables
      determined in the laboratory and subsequent fertility after artificial
      insemination. It is clear, however, that there is still a deficiency in
      predicting in vivo fertility results of semen samples. The present study intended
      to verify the efficiency of rapid and slow thermoresistance tests in predicting
      fertility of frozen semen of bulls. Sperm from 64 ejaculates of 39 Nelore bulls
      (Bos indicus), aged 2-10 years, were cryopreserved in 0.5 mL straws. Thawed
      straws containing 30 x 10(6) sperm were analyzed for seminal variables in the
      laboratory and used to inseminate 4920 cows to evaluate fertility in the field.
      The ejaculates were frozen in a Tris-based extender and samples were evaluated
      for total motility after rapid (46 degrees C/30 min) and slow (38 degrees C/5h)
      thermoresistance tests by conventional and computerized (CASA) methods. Sperm
      samples were grouped according to their ability to retain motility after
      thermoresistance testing: group 0 (0% motility), group 1 (1-20% total motility),
      group 2 (21-40% total motility) and group 3 (>40% total motility). Correlation
      and association between these groups and fertility diagnosed by rectal palpation
      at 90 days were verified. Chi-square test demonstrated no association between
      motility groups and fertility (P>0.25) and both rapid and slow thermoresistance
      tests had a lesser correlation to fertility (r=0.11 and 0.14, respectively).
      These results demonstrated that these tests are not reliable in predicting in
      vivo behavior of bull frozen semen and are not effective to estimate fertility.

PMID- 18707831
TI  - Sacral fusion as an aid in age estimation.
AB  - The degree of fusion at the anterior aspect of the sacral vertebrae has been
      scored in 242 male and female skeletons from the Lisbon documented collection,
      ranging from 16 to 59 years old in age. Statistical tests indicate a sex
      difference towards earlier fusion in young females compared with young males, as
      well as a clear association between degree of fusion and age. Similar results
      have been found by other authors in documented skeletal samples from Coimbra and
      Sassari, and the recommendations stated by these authors regarding age estimation
      have been positively tested in the Lisbon collection. Although more research from
      geographically diverse samples is required, a general picture of the pattern of
      sacral fusion and its associations with age and sex is emerging. We also provide
      a practical example of the usefulness of the sacrum for age estimation in a
      forensic setting, a mass grave from the Spanish Civil War. It is concluded that
      the scoring of the degree of fusion of the sacral vertebrae, specially of S(1-2),
      can be a simple tool for assigning skeletons to broad age groups, and it should
      be implemented as another resource for age estimation in the study of human
      skeletal remains.

PMID- 18707832
TI  - Restoration of stamp marks on steel components.
AB  - Stamp marks are used as a unique identification for a range of items, but these
      can be erased for criminal activities. Erased marks can sometimes be recovered by
      etching or magnetic means. The present study looked at the application of Fry's
      reagent to recover erased marks from steel. The investigation also demonstrated
      that Fry's reagent can deteriorate on storing and will require a longer etching
      time. The effect of different applied forces of stamping was investigated, and
      the depth of the underlying deformation was determined by etching after varying
      degrees of metal removal. The amount of metal needing to be removed depends on
      the force applied to the die. Metal removal also affects the time needed for
      recovery. The underlying structural change remains as a hidden identification
      mark, and could potentially be used by manufacturers as an unseen identifier. A
      model for the underlying deformation is proposed.

PMID- 18707833
TI  - [Computerized management of a medical department, disease-related group
      management, clinical research and evaluations].
AB  - The current French hospital reform is based on the disease-related group (DRG)
      approach and the constitution of bigger units pooling several departments of
      different specialties. This reform needed an efficient assessment of various
      medical activities. We report our experience of a medical table of our hospital
      activities used for 27 months. This medical table was made with a basic software
      integrating 24 parameters. The original concept was the translation of the
      specific final diagnosis for DRG defined by the site of infection. To create this
      medical table, we first simplified the conclusions of the patient's chart using a
      consensual and systematic plan. The number of patients per DRG and their
      evolution were therefore specifically determined. The medical table helped us in
      the daily management of our department, to identify the area of recruitment, the
      potential for heterogeneous care, allowing the implementation of protocols and
      their applications. Moreover, the table quantified morbidity and mortality,
      indicating our need for cooperation with other departments. All this data used
      medical-lexical terms, allowing other than economic analyses, even if this table
      identifies hospitalization-related costs, namely duration of hospital-stay,
      nosocomial infections and iatrogenic events. Finally, our table supports medical
      research and evaluation of practice. Our future goals are to introduce this table
      in several infectious-diseases units, and create specific tables for the main
      RDG, including economic parameters.

PMID- 18707834
TI  - High intensity focused ultrasound (HIFU) therapy for local treatment of
      hepatocellular carcinoma: role of partial rib resection.
AB  - OBJECTIVE: It has long been known that high intensity focused ultrasound (HIFU)
      can kill tissue through coagulative necrosis. However, it is only in recent years
      that practical clinical applications are becoming possible. Since the ribs have
      strong reflections to ultrasonic beams, they may affect the deposition of
      ultrasound energy, decreasing the efficacy of HIFU treatment and increasing the
      chance of adverse events when the intra-abdominal tumours concealed by ribs are
      treated. The aim of this study was to evaluate the influence of partial rib
      resection on the efficacy and safety of HIFU treatment. METHODS: This prospective
      study was approved by the ethics committee at Chongqing University of Medical
      Sciences. An informed consent form was obtained from each patient and family
      member. A total of 16 patients with hepatocellular carcinoma (HCC), consisting of
      13 males and 3 females, were studied. All patients had the successful HIFU
      treatment. To create a better acoustic pathway for HIFU treatment, all of the 16
      patients had the ribs that shield the tumour mass to be removed. Magnetic
      resonance imaging (MRI) was used to evaluate the efficacy of HIFU treatment.
      RESULTS: Sixteen cases had 23 nodules, including 12 cases with a single nodule, 1
      case with 2 nodules, 3 cases with 3 nodules. The mean diameter of tumours was
      7.0+/-2.1 cm (5-10 cm). According to TNM classification, 9 patients were
      diagnosed as stage II, 4 patients were stage III, and 3 patients were stage IV.
      Follow-up imaging showed an absence of tumour blood supply and shrinkage of all
      treated lesions. The survival rates at 1, 2, 3, 4, and 5 years were 100%, 83.3%,
      69.4%, 55.6%, and 55.6%, respectively. No serious complications were observed in
      the patients treated with HIFU. CONCLUSION: Partial rib resection can create a
      better acoustic pathway of HIFU therapy. Even though it is an invasive treatment,
      this measure offers patients an improved prospect of complete tumour ablation
      when no other treatment is available.

PMID- 18707835
TI  - High resolution T2 weighted liver MR imaging using functional residual capacity
      breath-hold with a 1.0-Tesla scanner.
AB  - PURPOSE: During acquisition of rapid high resolution (HR) T2 weighted (T2W) liver
      magnetic resonance (MR) images using a 1.0-Tesla (T) scanner, the liver is
      segmented into odd and even sections that are acquired at two different times
      using the multi-breath-hold (MBH) strategy. Misalignment between the two breath
      hold (B-H) images may result in the occurrence of a blind area and a decrease in
      diagnostic accuracy. Here, a functional residual capacity (FRC) B-H method was
      developed to overcome this problem. MATERIAL AND METHODS: Twenty-five volunteers
      were enrolled. The sagittal images were reconstructed from whole liver transverse
      images. When the B-H phases are different, misalignment may occur in the
      craniocaudal and anterior-posterior (AP) directions. In this study, misalignments
      of the abdominal wall were measured in the AP direction. The misalignment was
      compared between four B-H phases, maximum inspiration (MI), maximum expiration
      (ME), voluntary expiration (VE) and FRC using one-way repeated measures ANOVA.
      Differences between groups were compared using the t-test for multi-group
      comparisons. In addition, qualitative analysis of misalignment was performed
      between VE and FRC in 52 clinical patients and the chi(2) test was performed.
      RESULTS: The misalignment widths of FRC, ME, MI and VE B-Hs were 2.7+/-3.8, 6.4+/
      7.4, 9.1+/-8.4 and 6.0+/-6.7 mm, respectively. Misalignment of the liver position
      using FRC was significantly smaller than for the other B-H methods (p<0.05).
      Significant differences between the VE B-H and FRC B-H were also observed in the
      qualitative analysis (p<0.05). CONCLUSION: The liver positions obtained when
      using FRC B-H were significantly more reproducible than when using the other B-H
      methods. The FRC B-H method resulted in a reduction in the blind area and an
      extension of the diagnostic area to the whole liver.

PMID- 18707836
TI  - Enantioseparation of the antidepressant reboxetine.
AB  - The enantioseparation of reboxetine by HPLC was investigated using chiral
      stationary phases (CSPs) containing cellulose Tris(3,5-dimethylphenyl)carbamate
      on silica gel (Chiralcel OD column) as the chiral selector. Reversed phase HPLC
      was the technique of choice for the analytical enantioseparation of reboxetine,
      while the chiral semipreparative separation was obtained with the same CSP, but
      in normal phase conditions. The effects of the mobile phase pH and composition on
      analytical retention, enantioselectivity and resolution were investigated. The
      best performance was obtained using a mobile phase composed of 0.5M sodium
      perchlorate at pH 6 and acetonitrile in the 60/40 (v/v) ratio. The
      semipreparative separation has allowed obtaining pure enantiomers, but required
      the preparation of reboxetine free base. Different n-hexane/alcohol mixtures were
      tested as mobile phases, varying both the nature of the alcohol and its
      percentage in the mobile phase. Different n-hexane/alcohol mixtures were tested
      as mobile phase and the best results were obtained by using a mobile phase
      composed of n-hexane and 2-propanol (80:20, v/v).

PMID- 18707837
TI  - Chemiluminescence detection of opium poppy (Papaver somniferum) alkaloids.
AB  - A review with 98 references. The determination of the opium poppy (Papaver
      somniferum) alkaloids and their semi-synthetic derivatives has important
      applications in industrial process monitoring, clinical analysis and forensic
      science. Liquid-phase chemiluminescence reagents such as tris(2,2'
      bipyridyl)ruthenium(II) and acidic potassium permanganate exhibit remarkable
      sensitivity and complementary selectivity for many P. somniferum alkaloids, which
      has been exploited in the development of a range of analytical procedures using
      flow analysis, high-performance liquid chromatography, capillary electrophoresis
      and microfluidic instrumentation.

PMID- 18707839
TI  - Association between antibiotic usage and subsequent colonization or infection of
      extensive drug-resistant Acinetobacter baumannii: a matched case-control study in
      intensive care units.
AB  - Nosocomial spreading of extensive drug-resistant Acinetobacter baumannii (EDRAB)
      is an emerging problem. To clarify the association between prior antibiotic usage
      and subsequent EDRAB acquisition, we conducted a one-to-one matched case-control
      study among patients in all intensive care units (ICUs) at the National Taiwan
      University Hospital, Taipei, Taiwan, during a 1-year period. A total of 113 pairs
      of patients were identified. We measured prior antibiotics exposure in 4
      perspectives: usage, overall treatment duration, accumulated dosage, and
      treatment potency. We found positive associations between EDRAB acquisition and
      prior usage of imipenem and meropenem across 4 measures, especially in usage and
      average treatment potency (usage, odds ratio [OR](imipenem) = 3.7 with 95%
      confidence interval [CI] = 1.2-11.0, OR(meropenem) = 5.4 with 95% CI = 1.2-20.0;
      average treatment potency, OR(imipenem) = 5.3 with 95% CI = 1.3-22.0,
      OR(meropenem) = 3.4 with 95% CI = 1.0-12.0). Ceftazidime use with stronger
      treatment potency was also strongly associated with subsequent nosocomial EDRAB
      acquisition (OR = 5.5, 95% CI = 1.5-21.0). The OR of EDRAB acquisition greatly
      increased in patients who had previously been exposed to any 1 (OR = 5.5, 95% CI
      = 2.3-13.2) or to any 2 or 3 (OR = 11.1, 95% CI = 2.7-46.4) of the abovementioned
      antibiotics. Based on these findings, we conclude that usage of imipenem,
      meropenem, and/or ceftazidime is associated with subsequent acquisition of EDRAB
      in critically ill patients in ICUs.

PMID- 18707838
TI  - Development of multiplexed real-time quantitative polymerase chain reaction assay
      for detecting human adenoviruses.
AB  - Adenoviruses (AdVs) have been associated with a wide variety of human disease and
      are increasingly recognized as viral pathogens that can cause significant
      morbidity and mortality in immunocompromised patients. Early detection of AdV DNA
      in plasma and sterile fluids has been shown to be useful for identifying patients
      at risk for invasive AdV disease. Because of the large number of existing Adv
      types, few real-time quantitative AdV polymerase chain reaction (PCR) assays
      published effectively cover all AdV types. We designed a series of AdV PCR
      primers and probes and empirically multiplexed them into 2 separate real-time PCR
      assays to quantitatively detect all 49 serotypes of human AdV (types 1-49)
      available from American Type Culture Collection. We then subsequently multiplexed
      all the primers and probes into 1 reaction. The sensitivity of these assays was
      determined to be less than 10 copies per reaction (500 copies/mL plasma). In a
      retrospective evaluation, we detected all 84 clinical AdV isolates isolated in
      cell culture from patients undergoing hematopoietic stem cell transplantation
      between 1981 and 1987. Prospective analysis of 46 consecutive clinical samples
      submitted for AdV testing showed greater sensitivity and equal specificity of the
      AdV PCR than viral culture. This real-time PCR assay allows rapid, sensitive, and
      specific quantification of all currently defined AdVs into either 2 or 1
      multiplex assay for clinical samples.

PMID- 18707840
TI  - Development of a rapid assay methodology for antimicrobial susceptibility testing
      of Staphylococcus aureus.
AB  - Development of a new phenotypic technique for rapid antimicrobial susceptibility
      testing (AST) of methicillin-resistant Staphylococcus aureus is presented. The
      new technique combines bacterial culturing and specific immunometric detection in
      a single separation-free process. The technique uses dry chemistry reagents and
      the recently developed two-photon excitation detection technology, which allows
      online detection of bacterium-specific growth. The performance of the new
      technique was evaluated by monitoring the growth of S. aureus reference strains
      and determining their susceptibility to oxacillin. In the direct analysis of
      clinical specimens, method specificity and tolerance to interferences caused by
      other bacteria present in the sample are pivotal. Other bacteria can compete with
      the bacteria of interest for nutrients, for example. Specificity and tolerance
      were studied against Staphylococcus epidermidis reference strains. The results
      suggest that the new technique could allow rapid AST directly from clinical
      samples within 6 to 8 h. Such a rapid and simple testing methodology would be a
      valuable tool in clinical microbiology because it would shorten the turnaround
      times of microbiologic analyses. Advantages of the new approach in relation to
      conventional methods are discussed.

PMID- 18707841
TI  - Determination of in vitro susceptibility of ocular Fusarium spp. isolates from
      keratitis cases and comparison of Clinical and Laboratory Standards Institute M38
      A2 and E test methods.
AB  - We evaluated the susceptibility of 85 Fusarium spp. isolates from cases of fungal
      keratitis with 8 antifungal drugs using the standard Clinical and Laboratory
      Standards Institute broth microdilution and E test methods. Members of the
      Fusarium solani species complex showed consistently higher MICs to the triazole
      drugs itraconazole, voriconazole, and posaconazole than did members of other
      species complexes (Fusarium oxysporum and other minor species). High MICs to
      amphotericin B, natamycin, and echinocandins were consistently obtained with no
      discrimination based on species or method. Further work is required to determine
      any potential correlation between MIC and clinical outcome in keratitis.

PMID- 18707843
TI  - Live three-dimensional transesophageal echocardiography-guided transcatheter
      closure of a mitral paraprosthetic leak by Amplatzer occluder.
AB  - Recently introduced real-time 3-dimensional transesophageal echocardiography
      allows online accurate assessment of cardiac structures. Initial experience
      indicates that this new technique provides improved anatomic definition and novel
      views of complex cardiac abnormalities in valve anatomy. We demonstrated the
      utility of live 3-dimensional transesophageal echocardiography in the assisted
      transcatheter closure of a mitral prosthesis paravalvular leak by Amplatzer
      occluder.

PMID- 18707844
TI  - Modelling of chromatin morphologies in breast cancer cells undergoing apoptosis
      using generalized Cauchy field.
AB  - Chromatin morphologies in human breast cancer cells treated with an anti-cancer
      agent are analyzed at their early stage of programmed cell death or apoptosis.
      The gray-level images of nuclear chromatin are modelled as random fields. We used
      two-dimensional isotropic generalized Cauchy field to characterize local self
      similarity and global long-range dependence behaviors in the image spatial data.
      Generalized Cauchy field allows the description of fractal behavior inferred from
      fractal dimension and the long-range dependence inferred from correlation
      exponent to be carried out independently. We demonstrated the usefulness of
      locally self-similar random fields with long-range dependence for modelling
      chromatin condensation.

PMID- 18707845
TI  - Incorporating temporal information into active contour method for detecting heart
      wall boundary from echocardiographic image sequence.
AB  - A new method which incorporates temporal information into the active contour
      function is proposed to solve the dropout and speckle noise problems encountered
      when detecting the inner heart wall boundary from echocardiographic image
      sequence. The ventricular boundary is considered to be composed of strong and
      weak segments. The weak segments are interfered by image degradations in
      ultrasound, and they are too weak to constrain the curve evolution. Temporal
      information is incorporated into the external energy of the active contour
      function to recover the missing boundary and strengthen the weak segments.
      Experimental results demonstrate the advantages of the proposed method for the
      intended task.

PMID- 18707846
TI  - Inflammatory and prothrombotic biomarkers in patients with rheumatoid arthritis:
      effects of tumor necrosis factor-alpha blockade.
AB  - OBJECTIVE: Increased cardiovascular (CV) risk is a rheumatoid arthritis (RA)
      hallmark and it has been mainly related to chronic systemic inflammation. Since
      inflammation is linked to coagulation perturbation, both may play a role in
      increasing CV risk. Treatment with tumor necrosis factor (TNF)-alpha blocking
      agents is effective in RA and reduces local and systemic inflammation but there
      is little information on its effect on coagulation. We therefore investigated
      inflammation and coagulation plasma biomarkers before and after infliximab
      treatment in RA patients. METHODS: We studied 20 patients with active RA and 40
      healthy controls. Patients were treated with: a stable dose of methotrexate
      (10mg/week), and infliximab (3mg/kg) at weeks 0, 2, 6 and 14. At baseline and
      week 14, we determined: disease activity score (DAS-28), visual analogue scale
      pain, erythrocyte sedimentation rate (ESR), and plasma levels of C-reactive
      protein (CRP), TNF-alpha, interleukin (IL)-6, prothrombin fragment 1+2 (F1+2) and
      D-dimer. The same inflammation and coagulation parameters were evaluated 1h after
      infliximab infusion in 10 patients. RESULTS: At baseline, ESR, CRP, TNF-alpha, IL
      6, F1+2 and D-dimer levels were significantly higher in RA patients than in
      controls (P=0.0001). After 14weeks of infliximab treatment, there was a
      significant clinical improvement and ESR and CRP, IL-6, F1+2 and D-dimer level
      decrease (P=0.001-P=0.008). The levels of TNF-alpha, IL-6, F1+2 and D-dimer
      significantly decreased 1h after infliximab infusion (P=0.005). CONCLUSIONS:
      Infliximab decreases inflammation and coagulation biomarkers in RA patients. Such
      a combined effect may be pivotal in reducing the whole thrombotic risk in these
      patients.

PMID- 18707847
TI  - Container effects on the physicochemical properties of parenteral lipid
      emulsions.
AB  - OBJECTIVE: We evaluated the effects of glass and plastic containers on the
      physicochemical properties of parenteral nutrition lipid emulsions and total
      nutrient admixtures with an emphasis on globule size distribution and colloidal
      stability. METHODS: A commercial lipid emulsion, 20% ClinOleic, was separated
      into glass (type II soda-lime-silica) and plastic (polypropylene multilayer)
      containers, sterilized, and then stored for 16 wk at 40 degrees C. Globule size
      distribution, pH, and zeta potential measurements were made every 4 wk.
      Admixtures derived from parent lipid emulsions were tested after admixing (t =
      0), storage for 7 d at 5 degrees C plus 24 h at 25 degrees C (t = 7 + 1), and
      then after an additional 3 d at 25 degrees C (t = 7 + 4). RESULTS: The parent
      lipid emulsions in glass and plastic containers exhibited identical time
      dependent behavior with respect to mean globule size, percentage of oil droplets
      >or=5 mum, pH, and zeta potential measurements. The percentages of oil droplets
      >or=5 mum of all test conditions remained well below the United States
      Pharmacopeia <729> limits of 0.05%. The total nutrient admixture time-dependent
      physicochemical characteristics were also found to be independent of the parent
      lipid emulsion container type. CONCLUSION: Plastic and glass containers were
      found to be suitable, safe, and indistinguishable with respect to physicochemical
      stability of a representative parenteral nutrition lipid emulsion and total
      nutrient admixtures derived from the parent lipid emulsion.

PMID- 18707848
TI  - Prospective memory in schizophrenia: further clarification of nature of
      impairment.
AB  - Prospective memory (PM) refers to the ability to execute a delayed intention and
      is different from retrospective memory (RM) in its nature and underlying
      mechanism (e.g., intention formation, maintenance, detection of PM cue and
      intention execution). Although preliminary studies have found PM impairment in
      patients with schizophrenia, the nature and magnitude of this problem in this
      clinical group is not yet fully known. The current study aimed to further clarify
      the nature of this impairment in schizophrenia. Fifty-four patients with
      schizophrenia and fifty-four healthy volunteers matched on demographic variables,
      IQ and executive functions took part in the study. Time-, event-, and activity
      based PM tasks and a set of neurocognitive tests were administered to the
      participants. Results showed that patients with schizophrenia performed
      significantly worse on all sub-types of PM tasks, even after controlling for
      neurocognitive functions such as working memory, verbal memory, visual memory,
      and executive function. These findings suggest PM deficit is a primary deficit
      rather than a secondary consequence of neurocognitive impairments in
      schizophrenia. Analysis found that PM deficits may be mainly due to the
      impairment of the cue detection and intention retrieval stage.

PMID- 18707849
TI  - Immunomodulatory therapies for sepsis: unexpected effects with macrolides.
AB  - Despite intensive efforts to increase our knowledge of the inflammatory pathways
      involved in the pathogenesis of sepsis, several clinical trials of agents aimed
      at modulating the immune response of the host, such as anti-endotoxin antibodies,
      anti-tumour necrosis factor (TNF) antibodies and soluble TNF receptors, have
      failed to disclose any definite clinical benefit. The same applies to the
      administration of low-dose hydrocortisone as well as intense glucose control by
      continuous insulin infusion. Macrolides are a traditional class of antimicrobials
      proven to act as modulators of the host's response in chronic lung disorders such
      as diffuse panbronchiolitis and cystic fibrosis. The favourable outcome of
      community-acquired pneumonia treated with the combination of a beta-lactam and a
      macrolide is partly attributed to their immunomodulatory properties. Based on
      favourable responses to intravenous administration of clarithromycin in
      experimental models of sepsis by susceptible and multidrug-resistant Gram
      negative isolates, a randomised clinical trial was conducted in 200 patients with
      ventilator-associated pneumonia (VAP) and sepsis (http://www.clinicaltrials.gov;
      NCT00297674). Clarithromycin was administered at a dose of 1g within 1h of
      infusion for three consecutive days. Analysis revealed a considerable benefit of
      clarithromycin in shortening the time to resolution of VAP and to de-intubation
      from mechanical ventilation. The relative risk of death by septic shock and
      multiple organ dysfunction was 19.00 among placebo-treated patients; it was
      reduced to 3.78 among clarithromycin-treated patients. These results render new
      perspectives for the future application of clarithromycin as an immunomodulatory
      therapy of sepsis.

PMID- 18707850
TI  - Heterogeneity of bla(IND) metallo-beta-lactamase-producing Chryseobacterium
      indologenes isolates detected in Hefei, China.
AB  - This study investigated the phenotypic and genetic properties of 28 clinical
      isolates of metallo-beta-lactamase (MBL)-producing Chryseobacterium indologenes
      recovered from a university hospital. Twenty isolates were confirmed to carry a
      bla(IND) gene. Among them, 9 isolates were confirmed to carry the IND-1 gene, 10
      contained the IND-2 gene and 1 had bla(IND-3) alleles. One strain (No. 7)
      confirmed to be carrying the bla(IND-1) gene was susceptible to imipenem and was
      negative in phenotypic methods. The data revealed that the antimicrobial
      resistance patterns of C. indologenes harbouring MBL genes are remarkably
      distinct. Two specific types of MBL genes, bla(IND-1) and bla(IND-2), were
      identified to be the major genotype for C. indologenes isolated from Hefei,
      China.

PMID- 18707851
TI  - The recognition of facial emotion expressions in Parkinson's disease.
AB  - A limited number of studies in Parkinson's Disease (PD) suggest a disturbance of
      recognition of facial emotion expressions. In particular, disgust recognition
      impairment has been reported in unmedicated and medicated PD patients. However,
      the results are rather inconclusive in the definition of the degree and the
      selectivity of emotion recognition impairment, and an associated impairment of
      almost all basic facial emotions in PD is also described. Few studies have
      investigated the relationship with neuropsychiatric and neuropsychological
      symptoms with mainly negative results. This inconsistency may be due to many
      different problems, such as emotion assessment, perception deficit, cognitive
      impairment, behavioral symptoms, illness severity and antiparkinsonian therapy.
      Here we review the clinical characteristics and neural structures involved in the
      recognition of specific facial emotion expressions, and the plausible role of
      dopamine transmission and dopamine replacement therapy in these processes. It is
      clear that future studies should be directed to clarify all these issues.

PMID- 18707852
TI  - Cerebral metabolic patterns in untreated postmenopausal women with major
      depressive disorder.
AB  - Cerebral metabolic rates were assessed using [(18)F]-fluorodeoxyglucose positron
      emission tomography in six naturally postmenopausal women with untreated unipolar
      depression and 11 matched controls. All subjects were hormone therapy-naive and
      medication-free. Findings include hypermetabolism in the middle frontal gyrus and
      Broca regions, and hypometabolism in the pons among depressed compared with non
      depressed women.

PMID- 18707853
TI  - Danggui-Shaoyao-San, a traditional Chinese prescription, suppresses PGF2alpha
      production in endometrial epithelial cells by inhibiting COX-2 expression and
      activity.
AB  - Danggui-Shaoyao-San, a famous traditional Chinese prescription, has been widely
      used in China for treating various gynecological inflammatory diseases including
      dysmenorrhea, but it is still poorly understood how it works on those
      inflammatory disorders. Prostaglandin F(2alpha) (PGF(2alpha)), one important
      mediators of inflammation, plays crucial roles in the pathological mechanism
      responsible for dysmenorrhea. Here, we demonstrate that Danggui-Shaoyao-San
      significantly suppresses oxytocin-evoked PGF(2alpha) production of rat
      endometrial epithelial cells in a concentration-dependent manner. Furthermore,
      Danggui-Shaoyao-San-mediated down-regulation of cyclooxygenases-2 message RNA
      transcription, protein expression and enzyme activity in endometrial epithelial
      cells may be involved in the inhibitory effect on PGF(2alpha) production. Our
      study provides a possible mechanism for the bioactivity of Danggui-Shaoyao-San
      for treating dysmenorrhea and other gynecological disorders.

PMID- 18707854
TI  - Phytochemical composition and in vitro pharmacological activity of two rose hip
      (Rosa canina L.) preparations.
AB  - The aim of the present study was to compare powdered rose hip with and without
      fruits (Rosae pseudofructus cum/sine fructibus, Rosa canina L., Rosaceae) with
      regard to their phytochemical profile and their in vitro anti-inflammatory and
      radical-scavenging properties. The two powders were subsequently extracted with
      solvents of increasing polarity and tested for inhibition of cyclooxygenase (COX
      1, COX-2) and of 5-LOX-mediated leukotriene B(4) (LTB(4)) formation as well as
      for DPPH-radical-scavenging capacity. While the water and methanol extracts were
      inactive in the COX-1, COX-2 and LTB(4) inhibition assays, the n-hexane and the
      dichloromethane extracts inhibited all three enzymes. In the active extracts, the
      triterpenoic acids ursolic acid, oleanolic acid and betulinic acid were
      identified, although only in minute amounts. Furthermore, oleic, linoleic and
      alpha-linolenic acid were identified apart from several saturated fatty acids.
      Even though unsaturated fatty acids are known to be good inhibitors of COX-1, COX
      2 and LT formation, no clear correlation between their concentration in the
      extracts and their activity was found. We suggest that other, yet unidentified,
      lipophilic constituents might play a more important role for the observed in
      vitro inhibitory activity on arachidonic acid metabolism. Some of the extracts
      also showed considerable DPPH radical scavenging activity, the methanolic
      extracts being most potent. The radical scavenging activity of the extracts
      correlated very well with their total phenolic content, while ascorbic acid
      contributes only little to the radical-scavenging activity due to its low
      concentration present in the extracts. In summary, extracts derived from powdered
      rose hip without fruits were more effective in all assays carried out compared
      with extracts derived from powdered rose hip with fruits.

PMID- 18707855
TI  - Mogoltacin enhances vincristine cytotoxicity in human transitional cell carcinoma
      (TCC) cell line.
AB  - Bladder cancer is the second common cancer of the genitourinary system throughout
      the world and intravesical chemotherapy is usually used to reduce tumour
      recurrence and progression. Human transitional cell carcinoma (TCC) is an
      epithelial-like adherent cell line originally established from primary bladder
      carcinoma. Here we report the effect of mogoltacin, a sesquiterpene coumarin from
      Ferula badrakema on TCC cells. Mogoltacin was isolated from the fruits of F.
      badrakema, using silica gel column chromatography and preparative thin layer
      chromatography. Mogoltacin did not have any significant cytotoxicity effect on
      neoplastic TCC cells at 16, 32, 64, 128, 200 and 600 microg ml(-1)
      concentrations. In order to analyse its combination effect, TCC cells were
      cultured in the presence of various combining concentrations of mogoltacin and
      vincristine. Cells were then observed for morphological changes (by light
      microscopy) and cytotoxicity using MTT assay. The effect of mogoltacin on
      vincristine toxicity was studied after 24, 48 and 72 h of drug administration.
      The results of MTT assay showed that mogoltacin can significantly enhance the
      cytotoxicity of vincristine and confirmed the morphological observations. Results
      revealed that combination of 40 microg ml(-1) vincristine with 16 microg ml(-1)
      mogoltacin increased the cytotoxicity of vincristine after 48 h by 32.8%.

PMID- 18707856
TI  - Fourteen coprophilous species of Psathyrella identified in the Nordic countries
      using morphology and nuclear rDNA sequence data.
AB  - Psathyrella species growing on dung or occasionally on dung in the Nordic
      countries were studied using morphological characters and nu-rDNA sequence data
      and type collections were examined when available. Fourteen species capable of
      growing on dung were identified. Descriptions are given of all dung-inhabiting
      species and to a lesser extent of the species occasionally growing on dung. Three
      new species are described: Psathyrella fimiseda, P. merdicola, and P. scatophila.
      P. stercoraria is described as a new species in order to validate the name. A key
      to the coprophilous species in Europe including the species described by Peck &
      Smith from North America is provided. The phylogenetic analyses recovered four
      major supported clades within Psathyrellaceae corresponding to Parasola,
      Coprinopsis, Lacrymaria/Spadiceae pro parte, and Psathyrella. The status of
      Coprinellus was ambiguous. The current morphology-based infrageneric
      classification of Psathyrella was not supported by the phylogenetic analyses and
      a coprophilous habit has apparently evolved on multiple occasions. Three new
      combinations are proposed: Parasola conopilus, Coprinopsis marcescibilis, and
      Coprinopsis pannucioides.

PMID- 18707857
TI  - Regulation switching of Epichloe typhina within elongating perennial ryegrass
      leaves.
AB  - Epichloe and Neotyphodium spp. are clavicipitaceous fungi that form symbiotic
      endophytic associations with temperate grasses. The growth of these endophytes is
      strictly intercellular and tightly regulated, being synchronized with that of the
      host grass. The exception to this synchronized form of growth is the profuse
      growth of hyphae during development of stromata on reproductive tillers, thereby
      preventing emergence of the inflorescence. Here we report the occurrence of
      stromata on leaves of vegetative tillers of perennial ryegrass infected with E.
      typhina. Stroma formation was confined to leaf blades, being present as a
      distinct zone within an otherwise symptomless leaf. In some leaf blades two or
      more stromata zones were present, separated by symptomless tissue. Growth of
      hyphae in the symptomless zones was seldom branched, orientated parallel with the
      longitudinal leaf axis, and synchronised with plant growth. In contrast, hyphal
      growth in the stroma zones was unrestricted and highly branched. Thus in stable
      zones along a single leaf blade the interaction between E. typhina and its host
      grass alternated between synchronised, symptomless growth and a pathogenic state
      with unrestricted hyphal growth. These results demonstrate that the development
      of an inflorescence is not a prerequisite for hyphal growth leading to stroma
      formation and provide an ideal experimental system for investigating further how
      these fungi are able to switch from synchronized, symptomless growth to
      unrestricted stromal expression.

PMID- 18707859
TI  - Characterization of a mineral waste resulting from the melting treatment of air
      pollution control residues.
AB  - Air pollution control (APC) residues which are generated by municipal solid waste
      (MSW) incineration show a high-level of pollution potential. In order to
      stabilize such APC residues, the French power supply company (EDF) is developing
      a thermal treatment process which leads to the production of a vitrified
      material. A structural characterization of the vitrified product was carried out
      by applying complementary investigation methods: XRD, SEM, Raman spectroscopy,
      EPMA, and data interpretation methods such as mineralogical analysis and
      principal component analysis (PCA). The major phase of the material was a solid
      solution of melilite type composed of five end-members: gehlenite (44%),
      akermanite (25%), ferri-gehlenite (5%), sodamelilite (14%) and hardystonite
      (11%). The minor phases identified were spinels and pyroxenes. An ANC leaching
      test was performed in order to observe the treatment effect on pollutant release.
      The natural pH was close to 10, and the major element release was less than in
      the case of untreated APC. This was a consequence of melilite formation. The
      effect of pH was fundamental for heavy metals release: lower solubilization
      occurs at pH 10 than at APC's natural pH (11-12).

PMID- 18707858
TI  - Does the relationship between asthma and obesity differ by neighborhood?
AB  - BACKGROUND: Prior studies suggest that obesity may cause asthma. Obesity and
      asthma are prevalent in low-income urban neighborhoods, but the impact of obesity
      on asthma in such neighborhoods has not been examined. METHODS: The New York City
      Department of Health and Mental Hygiene surveyed 6119 adults age 18-54 years in
      2002. Obesity was defined as body mass index > or = 30 kg/m(2) and current asthma
      as physician diagnosed asthma plus recent symptoms. We calculated prevalence
      (risk) differences (RD) and population attributable risk percents (PAR%).
      RESULTS: Obese individuals had a 2.0% (95% CI: 0.5%, 3.6%; p=0.01) higher risk of
      current asthma than normal weight individuals overall. Obesity was more common in
      low-income neighborhoods compared with middle-to-upper-income neighborhoods (23%
      vs. 14%, p<0.001), as was current asthma (6% vs. 4%, respectively, p=0.02). The
      risk of current asthma associated with obesity was similar in low-income (RD:
      1.3%, 95% CI: -1.5%, 4.0%; p=0.36) and middle-to-upper-income neighborhoods (RD:
      2.0%, 95% CI: 0.1%, 3.9%; p=0.04). The PAR% for asthma due to obesity was not
      greater in low-income (7.3%) than in middle-to-upper-income neighborhoods (7.7%).
      CONCLUSIONS: It is unlikely that the excess asthma prevalence in urban low-income
      neighborhoods is disproportionately attributable to obesity. Instead, alternative
      causes of excess asthma should be sought.

PMID- 18707860
TI  - Model-based prediction of long-term leaching of contaminants from secondary
      materials in road constructions and noise protection dams.
AB  - In this study, contaminant leaching from three different secondary materials
      (demolition waste, municipal solid waste incineration ash, and blast furnace
      slag) to groundwater is assessed by numerical modeling. Reactive transport
      simulations for a noise protection dam and a road dam (a typical German
      autobahn), in which secondary materials are reused as base layers, were performed
      to predict the breakthrough of a conservative tracer (i.e., a salt) and sorbing
      contaminants (e.g., PAHs like naphthalene and phenanthrene or heavy metals) at
      the groundwater table. The dam constructions have a composite architecture with
      soil covers in inclined layers and distinct contrasts in the unsaturated
      hydraulic properties of the used materials. Capillary barrier effects result in
      strong spatial variabilities of flow and transport velocities. Contaminant
      breakthrough curves at the groundwater table show significant tailing due to slow
      sorption kinetics and a wide distribution of travel times. While conservative
      tracer breakthrough depends primarily on subsoil hydraulic properties,
      equilibrium distribution coefficients and sorption kinetics represent additional
      controlling factors for contaminant spreading. Hence, the three secondary
      materials show pronounced differences in the temporal development of leached
      contaminant concentrations with consequences for breakthrough times and peak
      concentrations at the groundwater table. Significant concentration reductions due
      to dispersion occur only if the source concentrations decrease significantly
      prior to the arrival of the contaminant at the groundwater table. Biodegradation
      causes significant reduction of breakthrough concentrations only if flow
      velocities are low.

PMID- 18707861
TI  - Microbiological characterization and specific methanogenic activity of anaerobe
      sludges used in urban solid waste treatment.
AB  - This study presents the microbiological characterization of the anaerobic sludge
      used in a two-stage anaerobic reactor for the treatment of organic fraction of
      urban solid waste (OFUSW). This treatment is one alternative for reducing solid
      waste in landfills at the same time producing a biogas (CH(4) and CO(2)) and an
      effluent that can be used as biofertilizer. The system was inoculated with sludge
      from a wastewater treatment plant (WWTP) (Rio Frio Plant in Bucaramanga-Colombia)
      and a methanogenic anaerobic digester for the treatment of pig manure (Mesa de
      los Santos in Santander). Bacterial populations were evaluated by counting groups
      related to oxygen sensitivity, while metabolic groups were determined by most
      probable number (MPN) technique. Specific methanogenic activity (SMA) for
      acetate, formate, methanol and ethanol substrates was also determined. In the
      acidogenic reactor (R1), volatile fatty acids (VFA) reached values of 25,000 mg
      L(-1) and a concentration of CO(2) of 90%. In this reactor, the fermentative
      population was predominant (10(5)-10(6)MPN mL(-1)). The acetogenic population was
      (10(5)MPN mL(-1)) and the sulphate-reducing population was (10(4)-10(5)MPN mL(
      1)). In the methanogenic reactor (R2), levels of CH(4) (70%) were higher than
      CO(2) (25%), whereas the VFA values were lower than 4000 mg L(-1). Substrate
      competition between sulphate-reducing (10(4)-10(5)MPN mL(-1)) and methanogenic
      bacteria (10(5)MPN mL(-1)) was not detected. From the SMA results obtained,
      acetoclastic (2.39 g COD-CH(4)g(-1)VSS(-1)day(-1)) and hydrogenophilic (0.94 g
      COD-CH(4)g(-1)VSS(-1)day(-1)) transformations as possible metabolic pathways used
      by methanogenic bacteria is suggested from the SMA results obtained. Methanotrix
      sp., Methanosarcina sp., Methanoccocus sp. and Methanobacterium sp. were
      identified.

PMID- 18707862
TI  - D-fructose detection based on the direct heterogeneous electron transfer reaction
      of fructose dehydrogenase adsorbed onto multi-walled carbon nanotubes synthesized
      on platinum electrode.
AB  - Multi-walled carbon nanotubes (MWCNTs) were synthesized on platinum plate
      electrodes by the chemical vapor deposition (CVD) method. From the results of X
      ray photoelectron spectroscopy and voltammetric investigation, the iron
      nanoparticles used as a catalyst for the MWCNT synthesis were enclosed with
      MWCNTs. The MWCNTs synthesized on the Pt plate (MWCNTs/Pt) electrode were
      immediately immersed into solutions of d-fructose dehydrogenase (FDH) to
      immobilize the enzyme onto the MWCNTs/Pt electrode surfaces. After the FDH was
      immobilized onto the MWCNTs/Pt electrode, a well-defined catalytic oxidation
      current based on FDH was observed from ca. -0.15V (versus Ag/AgCl/sat'd KCl),
      which was close to the redox potential of heme c as a prosthetic group of FDH.
      From an analysis of a plot of the catalytic current versus substrate, the
      calibration range for the fructose concentration was up to ca. 40mmoldm(-3), and
      the apparent Michaelis-Menten constant was evaluated to be 11+/-1mmoldm(-3).

PMID- 18707863
TI  - A novel hydrogen peroxide sensor based on the direct electron transfer of
      horseradish peroxidase immobilized on silica-hydroxyapatite hybrid film.
AB  - The direct electron transfer of immobilized horseradish peroxidase (HRP) on
      silica-hydroxyapatite (HAp) hybrid film-modified glassy carbon electrode (GCE)
      and its application as H(2)O(2) biosensors were investigated. On silica/HRP
      HAp/GCE, HRP displayed a fast electron transfer process accompanied with one
      proton participate in. This sensor exhibited an excellent electrocatalytic
      response to the reduction of H(2)O(2) without the aid of an electron mediator.
      The proposed biosensor showed good reproducibility and high sensitivity to
      H(2)O(2) with the detection limit of 0.35 microM. In the range of 1.0-100 microM,
      the catalytic reduction current of H(2)O(2) was proportional to H(2)O(2)
      concentration. The apparent Michaelis-Menten constant (k(m)(app)) of the
      biosensor was calculated to be 21.8 microM, exhibiting a high enzymatic activity
      and affinity for H(2)O(2).

PMID- 18707864
TI  - Microsatellite instability in sporadic colon carcinomas has no independent
      prognostic value in a Belgian study population.
AB  - Pathological stage is currently the most important determinant of colorectal
      cancer prognosis. Hence, identification of additional prognostic markers is
      warranted. This study aimed to analyse the prognostic relevance of microsatellite
      instability (MSI) in 241 colon and 90 rectal tumours, using a mononucleotide loci
      multiplex PCR assay and immunohistochemistry. Thirty (12.4%) colon tumours and
      one rectal tumour showed MSI. Although MSI was associated with proximal location
      and poor differentiation, no survival benefit was observed. The prognostic value
      of stage and differentiation was confirmed in this study. Analysis by stage
      revealed a longer overall (stage II/III) and disease free survival (stage II) for
      patients with well differentiated tumours. In addition, age and distal
      localisation were related to longer overall survival in stage II tumours. In
      conclusion, our findings show an association of MSI in sporadic colon tumours and
      certain clinical features; however, they do not suggest a survival benefit for
      MSI tumours.

PMID- 18707865
TI  - Interleukin-10 -1082 promoter polymorphism associated with gastric cancer among
      Asians.
AB  - Studies investigating the association between interleukin-10 (IL-10) -1082
      promoter polymorphism and gastric cancer risk report conflicting results. The
      objective of this study was to quantitatively summarise the evidence for such a
      relationship. Two investigators independently searched the Medline and Embase
      databases. This meta-analysis included 13 case-control studies, which included
      2227 gastric cancer cases and 3538 controls. The combined results based on all
      studies showed that there was no significant difference in genotype distribution
      [AA odds ratio (OR)=0.92, 95% confidence interval (CI)=0.73, 1.14; AG (OR=1.09,
      95% CI=0.87, 1.36); GG (OR=1.03, 95% CI=0.85, 1.25)] between gastric cancer and
      noncancer patients. When stratifying for race, results were similar except that
      patients with gastric cancer had a significantly lower frequency of AA (OR=0.71,
      95% CI=0.52, 0.97) and higher frequency AG (OR=1.53, 95% CI=1.15, 2.03) than
      noncancer patients among Asians. When stratifying by the location of gastric
      cancer, we found that patients with cardia gastric cancer had a significantly
      lower frequency of AA (OR=0.53, 95% CI=0.34, 0.83) and higher frequency AG
      (OR=1.50, 95% CI=1.06, 2.11) than those with noncardia gastric cancer among
      Caucasians. When stratifying by the Lauren's classification of gastric cancer, we
      observed no statistically significant differences in genotype distribution. This
      meta-analysis suggests that the IL-10 -1082 promoter polymorphism may be
      associated with gastric cancer among Asians, and that differences in genotype
      distribution may be associated with the location of gastric cancer.

PMID- 18707866
TI  - Gastric MALT lymphoma: epidemiology and high adenocarcinoma risk in a nation-wide
      study.
AB  - BACKGROUND: Gastric marginal zone non-Hodgkin lymphomas MALT type (gMALT) and
      gastric adenocarcinomas (GC) are long-term complications of chronic Helicobacter
      pylori gastritis, however, the incidence of gMALT and the GC risk in these
      patients is unclear. OBJECTIVE: To evaluate epidemiological time trends of gMALT
      in the Netherlands and to estimate GC risk. METHODS: Patients with a first
      diagnosis of gMALT between 1991 and 2006 were identified in the Dutch nation-wide
      histopathology registry (PALGA). Age-standardised incidence rates were
      calculated. The incidences of GC in patients with gMALT and in the Dutch
      population were compared. Relative risks were calculated by a Poisson Model.
      RESULTS: In total, 1419 patients were newly diagnosed with gMALT, compatible with
      an incidence of 0.41/100,000/year. GC was diagnosed in 34 (2.4%) patients of the
      cohort. Patients with gMALT had a sixfold increased risk for GC in comparison
      with the general population (p<0.001). This risk was 16.6 times higher in gMALT
      patients aged between 45 and 59 years than in the Dutch population (p<0.001).
      CONCLUSIONS: GC risk in patients with gMALT is six times higher than in the Dutch
      population and warrants accurate re-evaluation after diagnosis and treatment for
      gMALT.

PMID- 18707867
TI  - Statins and cancer: A systematic review and meta-analysis.
AB  - BACKGROUND: Systematic reviews on the association between statin therapy and
      cancer have focused on randomised trials without assessing the quality of
      evidence. We aimed to review the overall evidence taking study quality into
      consideration. METHODS: Publications of original studies on the effect of statin
      treatment on cancer in adult patients were searched on MEDLINE, EMBASE and
      CENTRAL databases upto October 2007. Our search yielded 37 eligible original
      studies out of 3607 references. Five studies were additionally found through
      manual search. Thus, 42 studies were included in the analyses: 17 randomised
      controlled trials, 10 cohort studies, and 15 case-control studies. FINDINGS:
      Statins had no effect on the overall incidence of cancer (median risk ratio (RR)
      0.96, range 0.72 to 1.2), or on the incidence of lung (median RR 0.92, range 0.83
      to 3.0), breast (median RR 1.04, range 0.74 to 19) or prostate cancer (median RR
      0.96, range 0.33 to 1.7). They seemed to protect from stomach (median RR 0.59,
      range 0.40 to 0.88) and liver cancer (median RR 0.62, range 0.33 to 1.2), and
      from lymphoma (median RR 0.74, range 0.28 to 2.2). They increased the incidence
      of both melanoma (median RR 1.5, range 1.3 to 1.7) and non-melanoma skin cancer
      (median RR 1.6, range 1.2 to 2.2). The effect varied, yet inconsistently, by
      statin type. The median follow-up time was 4 years. The strength of evidence was
      mostly weak. INTERPRETATION: The evidence suggests that statins do not have short
      term effects on cancer risk. The evidence on potentially protective or harmful
      effects is inconclusive. High quality cohort studies with long follow-up are
      needed to resolve the issue.

PMID- 18707868
TI  - A diagnostic model to detect silent brain metastases in patients with non-small
      cell lung cancer.
AB  - We aimed to discriminate subgroups according to the risk of brain metastases in
      patients with non-small cell lung cancer (NSCLC) lacking neurological symptoms.
      We performed a retrospective review of 433 patients with NSCLC who underwent
      chest computed tomography (CT), brain magnetic resonance imaging (MRI) and bone
      scans at an initial staging work-up between April 2003 and April 2007. Brain
      metastases were determined by MRI. Patients were stratified into groups according
      to the number of risk factors (0-3) identified by multivariate analysis. In
      multivariate analysis, histopathology with non-squamous cell carcinoma, nodal
      stage 2 on CT and presence of bone metastases were three risk factors for brain
      metastases. Patients were divided into four groups according to the number (0-3)
      of these predictive factors. The proportions of patients with brain metastases in
      the four groups were 2%, 3%, 17% and 35%, respectively, and these differences
      were significant (P<0.001). When analysis was performed in patients with
      localised disease, the number of risk factors was correlated with the prevalence
      of brain metastases (P=0.013) but stage was not (P=0.153). Although this
      diagnostic model should be validated through further studies, our data suggest
      that the number of risk factors might be a useful tool to identify silent brain
      metastases in patients with NSCLC.

PMID- 18707870
TI  - Raltitrexed (Tomudex) versus standard leucovorin-modulated bolus 5-fluorouracil:
      Results from the randomised phase III Pan-European Trial in Adjuvant Colon Cancer
      01 (PETACC-1).
AB  - OBJECTIVES: PETACC-1 assessed if raltitrexed is non-inferior to 5-fluorouracil
      and leucovorin for relapse-free survival (RFS) and overall survival (OS) in
      adjuvant stage III colon cancer. METHODS: Non-inferiority required both HR for
      RFS and OS<1.25 at 1-sided alpha=0.05. Patients (1921) were randomised to six
      cycles of 5-FU/LV (n=969) or eight cycles of raltitrexed (n=952). We report the
      final results in 993 eligible patients who started and completed the allocated
      treatment (489 5-FU/LV and n=504 Raltitrexed) of whom respectively 146 and 148
      died, respectively. RESULTS: The trial closed prematurely when 17 (1.9%)
      raltitrexed-related deaths were reported. Haematological and gastrointestinal
      toxicities were more frequent with 5-FU/LV, liver toxicities with raltitrexed.
      Raltitrexed was stopped for toxicity in 13.2% and 5-FU/LV in 8.5%. Sixty-day
      mortality was 9% versus 7%. With 4.1 years median follow-up, the HR for RFS was
      1.16 (90% CI 0.99-1.37) and that for OS was 1.01 (90% CI 0.84-1.23). CONCLUSION:
      The trial failed to demonstrate non-inferiority of raltitrexed. FUNDING: Free
      drugs and financial support from AstraZeneca.

PMID- 18707871
TI  - Diabetes mellitus, body size and bladder cancer risk in a prospective study of
      Swedish men.
AB  - Epidemiologic studies on diabetes and body size in relation to risk of bladder
      cancer have yielded inconsistent results. We examined prospectively the
      associations between a history of diabetes, height, weight, body mass index and
      waist circumference, and the incidence of bladder cancer in the Cohort of Swedish
      Men, a prospective study of 45,906 men aged 45-79 years at baseline. During
      follow-up from 1998 through December 2007, 414 incident cases of bladder cancer
      were ascertained. A history of diabetes was not associated with risk of bladder
      cancer (multivariate rate ratio=1.16; 95% confidence interval=0.81-1.64).
      Similarly, no associations were observed for height, weight, body mass index or
      waist circumference. These findings in men do not support a role for diabetes,
      height or excess body mass in the aetiology of bladder cancer.

PMID- 18707872
TI  - The First European Conference on Infections in Leukaemia - ECIL1: a current
      perspective.
AB  - The First European Conference on Infections in Leukaemia - ECIL1 - was organised
      under the auspices of the Infectious Diseases Group of the European Organisation
      for Research and Treatment of Cancer (EORTC), the Infectious Diseases Working
      Party of the European Group for Blood and Bone Marrow Transplantation (EBMT), the
      Supportive Care Group of the European LeukaemiaNet (ELN) and the International
      Immunocompromised Host Society (ICHS). The objective of the meeting was to
      develop evidence-based guidelines for the management of bacterial and fungal
      infections in high-risk immunocompromised adult leukaemia patients and
      hematopoietic stem cell transplantation recipients. The conference was held on
      September 30th and October 1st, 2005 in Juan-les-Pins, France and brought
      together a panel of 59 expert haematologists, oncologists, microbiologists,
      infectious disease specialists and clinical trialists from across Europe, Israel
      and Australia. The ECIL1 Guidelines were formulated after lengthy discussion,
      debate and panel consensus on the findings from a relevant comprehensive
      literature search, results of a European current practice questionnaire and other
      international guidelines, specific to each of the six clinical areas examined.
      The final recommendations, published in the Supplements of this journal as a
      series of six manuscripts in 2007, were well received by the medical community.
      The ECIL1 organisers anticipated the need for regular review of these guidelines
      and the Second ECIL Conference was held in September 2007. Publication of the
      updated and expanded ECIL2 Guidelines is forthcoming. This paper provides a
      concise summary of the methodology and main recommendations of the ECIL1
      Guidelines.

PMID- 18707869
TI  - Endometrioid and clear cell ovarian cancers: a comparative analysis of risk
      factors.
AB  - Endometrioid and clear cell subtypes of ovarian cancer are both known to be
      closely associated with endometriosis and endometrial pathology, and so have
      often been combined in studies of causation. We have examined these ovarian
      cancers separately for potentially distinct risk factors in our population-based,
      Australia-wide case control study of 142 women with incident invasive
      endometrioid, 90 with clear cell ovarian cancers and 1508 population controls.
      Multivariate logistic regression was used to calculated odds ratios (ORs) and 95%
      confidence intervals (CIs). Increasing parity, and hormonal contraceptive use for
      > or = 5 years, strongly decreased the risks of both subtypes. Breast feeding and
      tubal ligation were also inversely associated, but significantly so only for the
      endometrioid subtype. As expected endometriosis increased the risk of both
      subtypes (OR 2.2, 95% CI 1.2-3.9 for endometrioid and OR 3.0, 95% CI 1.5-5.9 for
      clear cell). Obesity was associated only with clear cell cancers, where we
      observed a two-fold increased risk (OR 2.2, 95% CI 1.2-4.1). Also a significant
      trend of decreasing risk with increasing intensity of smoking (p trend 0.02) and
      education beyond high school was associated with decreased development of clear
      cell cancers only. Endometrioid and clear cell ovarian cancers have some shared
      as well as some distinct risk factors, and therefore should be considered
      separately in studies of ovarian cancer.

PMID- 18707873
TI  - Treatment of primary rectal squamous cell carcinoma by primary chemoradiotherapy:
      should surgery still be considered a standard of care?
AB  - Rectal squamous cell carcinoma is a rare tumour accounting for only 0.25% of all
      rectal carcinomas, yet it carries a significant mortality and morbidity. Radical
      surgery has been advocated as the primary treatment modality with or without
      adjunctive therapies despite the proven benefits of primary chemoradiotherapy for
      squamous cell carcinoma (SCC) of the anus. This report describes 7 cases of
      rectal squamous cell carcinoma from a single institution over a four-year period,
      treated with primary chemoradiotherapy. All patients demonstrated significant
      tumour regression, and surgery to the primary tumour was avoided in all but one
      of these cases. Primary chemoradiotherapy can achieve excellent local control for
      rectal squamous cell carcinoma with surgery employed only for unresponsive or
      recurrent tumours.

PMID- 18707874
TI  - Bending properties of wood treated with a new organic wood preservative system.
AB  - This study investigated the effect of treatment of southern pine with a new
      generation, all organic wood preserving system on the mechanical properties in
      bending. Static bending tests showed no deleterious effects of treatment on
      property values when compared with untreated controls. Values for samples treated
      to 0.774 kg/m(3) total active ingredients (ai) were lower when compared to a
      lower retention (0.184 kg/m(3)) or to a standard copper azole system, but were
      not different than water-treated controls.

PMID- 18707875
TI  - Efficient hydrolysis of hemicellulose by a Fusarium graminearum xylanase blend
      produced at high levels in Escherichia coli.
AB  - A Fusarium graminearum-based enzyme blend for the efficient hydrolysis of
      hemicellulose, a crucial step for competitive bioethanol production, is
      described. The heretofore-uncharacterized endo-1,4-beta-xylanase (XylD), 1,4-beta
      xylosidase (XyloA), and bifunctional xylosidase/arabinofuranosidase (Xylo/ArabA)
      were produced at high levels in Escherichia coli (10-38 mg/l). They displayed
      compatible pH and temperature-dependences, allowing their utilization for
      simultaneous substrate digestions. Monosaccharide analysis indicated a strong
      positive synergism between the enzymes during the degradation of oat spelt xylan.
      Two units of each protein catalyzed the release of 61% and 15% of the total
      amount of available d-xylose and l-arabinose, respectively, in only 4 h. The
      detailed cooperative mechanism of the three hydrolases was elucidated by
      polysaccharide analysis using carbohydrate gel electrophoresis (PACE) and the
      enzymes were shown to be suitable for the partial hydrolysis of pretreated crude
      plant biomass.

PMID- 18707876
TI  - Nitrogen removal via nitrite in a sequencing batch reactor treating sanitary
      landfill leachate.
AB  - The present paper reports the results of the application of a control system,
      based on artificial intelligence concepts, for the automation of a bench-scale
      SBR treating leachate generated in old landfills. Attention was given to the
      nitritation and denitritation processes in order to enhance the nitrogen removal
      efficiency. Nitrification and nitrogen removal were usually higher than 98% and
      95%, respectively, whereas COD removal was approximately 20-30% due to the low
      biodegradability of organic matter in the leachate from old landfills; therefore,
      external COD was added to accomplish the denitrification process. Adjusting the
      length of the oxic phase, almost complete inhibition of the nitrite oxidizing
      organisms was observed. The results confirm the effectiveness of the nitrite
      route for nitrogen removal optimisation in leachate treatment. A significant
      saving of approximately 35% in external COD addition was achieved.

PMID- 18707877
TI  - Increased biogas production at wastewater treatment plants through co-digestion
      of sewage sludge with grease trap sludge from a meat processing plant.
AB  - The feasibility of co-digesting grease trap sludge from a meat-processing plant
      and sewage sludge was studied in batch and reactor experiments at 35 degrees C.
      Grease trap sludge had high methane production potential (918 m(3)/tVS(added)),
      but methane production started slowly. When mixed with sewage sludge, methane
      production started immediately and the potential increased with increasing grease
      trap sludge content. Semi-continuous co-digestion of the two materials was found
      feasible up to grease trap sludge addition of 46% of feed volatile solids
      (hydraulic retention time 16d; maximum organic loading rate 3.46 kgVS/m(3)d).
      Methane production was significantly higher and no effect on the characteristics
      of the digested material was noticed as compared to digesting sewage sludge
      alone. At higher grease trap sludge additions (55% and 71% of feed volatile
      solids), degradation was not complete and methane production either remained the
      same or decreased.

PMID- 18707878
TI  - Expression of soluble versatile peroxidase of Bjerkandera adusta in Escherichia
      coli.
AB  - Versatile peroxidase from white rot fungus Bjerkandera adusta was over-expressed
      in a soluble form in Escherichia coli. In the constructed enzyme model based on
      the selected gene from B. adusta, the active sites for oxidation of Mn(2+) ions
      and for oxidation of aromatic substrates were identified, both characteristic for
      versatile peroxidase. For over-expression of the recombinant enzyme different
      host strains, media formulations, growth temperatures, and fusion partners were
      tested. With the bacterial strain BL21(DE3)pLysS cultivated at 25 degrees C in
      auto-induction medium and presence of heme, a soluble peroxidase with
      incorporated heme and activity against different substrates was obtained. By
      exploiting an appropriate expression system and providing suitable culture
      conditions, the recombinant fungal peroxidases in soluble form can be produced in
      bacteria.

PMID- 18707879
TI  - Synthesis and evaluation of indolinyl- and indolylphenylacetylenes as PET imaging
      agents for beta-amyloid plaques.
AB  - Two new phenylacetylene derivatives, 5-((4-(2-(2-(2
      fluoroethoxy)ethoxy)ethoxy)phenyl)ethynyl)indoline 8 and 5-((4-(2-(2-(2
      fluoroethoxy)ethoxy)ethoxy)phenyl)ethynyl)-1H-indole 14, targeting beta-amyloid
      (Abeta) plaques have been prepared. In vitro binding carried out in tissue
      homogenates prepared from postmortem AD brains with [(125)I]IMPY (6-iodo-2-(4'
      dimethylamino-)phenyl-imidazo[1,2-a]pyridine) as the radioligand indicated good
      binding affinities (K(i)=4.0 and 1.5nM for 8 and 14, respectively). Brain
      penetration of the corresponding radiofluorinated ligands, evaluated in the
      normal mice, showed good initial brain penetration (4.50 and 2.43% ID/g (injected
      dose/gram) for [(18)F]8 and [(18)F]14 at 2min after injection) with moderate to
      low washout rates from the brain (1.71% ID/g at 2h and 2.10% ID/g at 3h,
      respectively). Autoradiography and homogenate binding studies demonstrated the
      high specific binding of [(18)F]14 to the Abeta plaques; however, [(18)F]8 showed
      low specific binding. These preliminary results identified that
      indolylphenylacetylene, 14, may be a good lead for further structural
      modification to develop a useful Abeta plaque imaging agent.

PMID- 18707880
TI  - Aglycone exploration of C-arylglucoside inhibitors of renal sodium-dependent
      glucose transporter SGLT2.
AB  - Inhibition of sodium-dependent glucose transporter 2 (SGLT2), the transporter
      that is responsible for renal re-uptake of glucose, leads to glucosuria in
      animals. SGLT-mediated glucosuria provides a mechanism to shed excess plasma
      glucose to ameliorate diabetes-related hyperglycemia and associated
      complications. The current study demonstrates that the proper relationship of a
      4'-substituted benzyl group to a beta-1C-phenylglucoside is important for potent
      and selective SGLT2 inhibition. The lead C-arylglucoside (7a) demonstrates
      superior metabolic stability to its O-arylglucoside counterpart (4) and it
      promotes glucosuria when administered in vivo.

PMID- 18707881
TI  - Synthesis and cytotoxic activity of some novel polycyclic gamma-butyrolactones.
AB  - Baeyer-Villiger oxidation of 5-aryl-7,11,11-trimethyltricyclo[5.4.0.0(3,6)]-undec
      1-en-4-ones 4a-h by H(2)O(2) and formic acid in methanol yields mixtures of
      3b,7,7-trimethyl-3-phenyl-3,3a,3b,4,5,6,7,8a-octahydro-1H-indeno-[1,2-c]furan-1
      ones 8a-h and 3b,7,7-trimethyl-3-phenyl-3,3a,3b,4,5,6,7,8a-octahydro-1H-indeno
      [1,2-c]furan-2-ones 9a-h in high yields. The obtained butyrolactones 8a-h display
      cytotoxic activity against a number of human cancer cells.

PMID- 18707882
TI  - Evidences for complex formation between L-dabPNA and aegPNA.
AB  - Continuing our research on the development of nucleopeptides as ODN analogs for
      biomedical and bioengineering applications, here we report the synthesis and the
      chemical-physical characterization of a homoadenine hexamer based on a l
      diaminobutyric acid (l-DABA) backbone (dabPNA), and its binding studies with a
      complementary aegPNA. We demonstrated by CD and UV experiments that the l-dabPNA
      binds the aegPNA forming a complex with good thermal stability, that we
      identified as a left-handed triplex.

PMID- 18707883
TI  - Flavylium salts as in vitro precursors of potent ligands to brain GABA-A
      receptors.
AB  - The synthesis of a series of derivatized flavylium cations was undertaken and the
      affinity to the benzodiazepine binding site of the GABA-A receptor evaluated. The
      observed high affinity for some derivatives (sub-muM range) was explained by an
      in vitro transformation of the flavylium cations into the corresponding trans
      retrochalcones, components which are proposed to be the active species in this
      series.

PMID- 18707884
TI  - A 4-aminobenzoic acid derivative as novel lead for selective inhibitors of
      multidrug resistance-associated proteins.
AB  - We present a novel lead for inhibitors of multidrug resistance-associated
      proteins (MRPs). Compound 1 (4-[(5,6,7,8-tetrahydro-4-oxo-4H-[1]benzothieno[2,3
      d][1,3]thiazin-2-yl)amino]benzoic acid) was about six times more potent than the
      known inhibitor MK571 at MRP1, while at MRP2 its effect was similar to that of
      MK571. Structural analogs were also evaluated. Among them, compound 2, sharing
      the 4-aminobenzoic acid substructure with 1, also inhibited MRP1. Both
      derivatives were inactive against P-gp. It can be concluded that their carboxyl
      group is needed for inhibition of MRPs and accounts for the selectivity of these
      compounds.

PMID- 18707885
TI  - The power of one.

PMID- 18707886
TI  - Campylobacter sugars sticking out.
AB  - The amazing repertoire of glycoconjugates that are found in Campylobacter jejuni
      includes lipooligosaccharides mimicking human glycolipids, capsular
      polysaccharides with complex and unusual sugars, and proteins that are post
      translationally modified with either O- or N-linked glycans. Thus, the glycome of
      this important food-borne pathogen is an excellent toolbox for glycobiologists to
      understand the fundamentals of these pathways and their role in host-microbe
      interactions, develop new techniques for glycobiology and exploit these pathways
      for novel diagnostics and therapeutics. The exciting surge in recent research
      activities will be summarized in this review.

PMID- 18707887
TI  - Cerebellar diaschisis and contralateral thalamus hyperperfusion in a stroke
      patient with complex regional pain syndrome.
AB  - We present a right-hemispheric stroke patient with complex regional pain syndrome
      (CRPS). The regional cerebral blow flow (rCBF) as determined using single photon
      emission computed tomography (SPECT) showed contralateral increase of tracer
      uptake in the left thalamus accompanied by crossed cerebellar diaschisis (CCD) in
      the left cerebellum. After rehabilitation, the CRPS in the right upper extremity
      recovered, although hemiplegia persisted on the left limbs. The rCBF determined a
      second time using SPECT showed that uptake was normal in the bilateral thalami,
      basal ganglia and bilateral cerebella. At a 6-month follow-up, the CRPS had not
      recurred. Our findings show that analysis of rCBF by SPECT is useful for the
      clinical evaluation and follow-up of CRPS. To the best of our knowledge, this is
      the first reported case with this particular pattern of symptoms amd symptom
      resolution.

PMID- 18707888
TI  - The enlightening encounter between structure and function in the NhaA Na+-H+
      antiporter.
AB  - Na(+)-H(+) antiporters are integral membrane proteins that exchange Na(+) for
      H(+) across the cytoplasmic membrane and many intracellular membranes. They are
      essential for Na(+), pH, and volume homeostasis, which are processes crucial for
      cell viability. Accordingly, antiporters are important drug targets in humans and
      underlie salt resistance in plants. Many Na(+)-H(+) antiporters are tightly
      regulated by pH. Escherichia coli NhaA, a prototype pH-regulated antiporter,
      exchanges 2H(+) for 1Na(+) (or Li(+)). The NhaA crystal structure has provided
      insight into the pH-regulated mechanism of antiporter action and revealed
      transmembrane segments, which are interrupted by extended mid-membrane chains
      that have since been found with variations in other ion-transport proteins. This
      novel structural fold creates a delicately balanced electrostatic environment in
      the middle of the membrane, which might be essential for ion binding and
      translocation.

PMID- 18707889
TI  - Dragging (and zooming and rotating) publication of 3D molecular structures into
      the 21st century.

PMID- 18707890
TI  - Hybridization-dependent fluorescence of oligodeoxynucleotides incorporating new
      pyrene-modified adenosine residues.
AB  - We report the synthesis and properties of oligonucleotides incorporating N(6)-[N
      (pyren-1-ylmethyl)carbamoyl]-deoxyadenosine (dA(pymcm)). We designed the ODN
      which incorporated two consecutive dA(pymcm) residues. It was revealed that on
      hybridization with the target DNA and RNA oligomers, the fluorescence spectra of
      ODNs having two consecutive dA(pymcm) molecules near the 5'-terminal position can
      change from the pyrene monomer emission to the excimer, depending on the chain
      length of the target DNA and RNA. These results indicated that dA(pymcm)-modified
      ODNs can be used as interesting hybridization sensors that are sensitive to the
      size of the target strand.

PMID- 18707891
TI  - Oleanolic acid and its derivatives: new inhibitor of protein tyrosine phosphatase
      1B with cellular activities.
AB  - Protein tyrosine phosphatase 1B is a key factor in the negative regulation of
      insulin pathway and a promising target for treatment of diabetes and obesity.
      Herein, a series of competitive inhibitors were optimized from oleanolic acid, a
      natural triterpenoid identified against PTP1B by screening libraries of
      traditional Chinese medicinal herbs. Modifying at 3 and 28 positions, we obtained
      compound 13 with a K(i) of 130 nM, which exhibited good selectivity between other
      phosphatases involved in insulin pathway except T-cell protein tyrosine
      phosphatase. Further evaluation in cell models illustrated that the derivatives
      enhanced insulin receptor phosphorylation in CHO/hIR cells and also stimulated
      glucose uptake in L6 myotubes with or addition of without insulin.

PMID- 18707892
TI  - Design and synthesis of carborane-containing androgen receptor (AR) antagonist
      bearing a pyridine ring.
AB  - We previously developed carborane-containing potent AR antagonists, BA321 and
      BA341, on the basis of our hypothesis that the carborane cage would be an
      excellent hydrophobic pharmacophore in place of steroidal C and D rings. As an
      extension of that work, we designed and synthesized carborane-containing AR
      antagonist candidates with a pyridine ring. Compound 6b, which has a pyridine
      ring directly bound to the p-carborane cage at the 3-position, exhibited potent
      AR-antagonistic activity in transcriptional activation assay using NIH3T3 cells
      transfected with a hAR-expression plasmid. In addition, it showed more potent
      antiandrogenic activity than that of the well-known antiandrogen flutamide and
      comparable activity to that of (R)-bicalutamide in SC-3 cell proliferation assay.

PMID- 18707893
TI  - Direct whole-mount imaging of fungal spores by energy-filtering transmission
      electron microscopy.
AB  - Whole-mount fungal spores were examined by energy-filtering transmission electron
      microscopy. Conidia of Penicillium species and Ustilaginoidea virens were
      suspended in distilled water and directly placed on a glow-discharged formvar
      coated copper grid. Energy-filtered images were taken from 0 to 100eV loss
      regions. Due to their considerable inherent thickness, their globose morphology
      was evident. In zero-loss images, the fungal spores appeared to have higher
      contrast in general, showing darker periphery than unfiltered images. Most spores
      in zero-loss images exhibited almost homogeneous electron density across the
      spores. The contrast was partially inversed in low-loss images where more details
      of the outer cell wall ornamentations of spores could be discerned than zero-loss
      images. As obvious advantages of whole-mount spore imaging, it allows for
      ensuring two-dimensional images with higher spatial resolution than light
      microscopy and conventional scanning electron microscopy. If a higher resolution
      is needed to observe fungal surface structures such as fimbriae and rodlet
      layers, or discriminate an outer sheath enveloping spores, whole-mount spore
      imaging can be employed to unravel structural details.

PMID- 18707894
TI  - Structural insights into histone H3 lysine 56 acetylation by Rtt109.
AB  - Histone acetylation plays important roles for the regulation of many fundamental
      cellular processes. Saccharomyces cerevisiae Rtt109 is an important class of
      histone acetyltransferases (HATs), which promote genome stability by directly
      acetylating newly synthesized histone H3 lysine 56 (H3-K56) through an unknown
      mechanism. Here, we report the crystal structures of Rtt109 at 2.2 A and
      Rtt109/Acetyl-CoA binary complex at 1.9 A. The structure displays a vise-like
      topology with mixed three-layered alpha/beta module forming the central module,
      whose core region resembles the structure of GCN5 HAT domain and P300/CBP HAT
      domain. Using structural and biochemical analyses, we have discovered the
      catalytic active site and have identified Asp288 as the deprotonation residue and
      Lys290 as the autoacetylation residue. We have further proposed the unique H3-K56
      anchoring pocket and the potential H3alphaN binding groove. Our work has provided
      structural insights to understand the acetylation mechanism of H3-K56 by Rtt109.

PMID- 18707895
TI  - Measurement of cross sections for the 147Sm(n, alpha)144Nd reaction at 5.0 and
      6.0 MeV.
AB  - Cross sections of the (147)Sm(n, alpha)(144)Nd reaction were measured at En=5.0
      and 6.0MeV. A twin gridded ionization chamber was used as a charged particle
      detector and two large area (147)Sm(2)O(3) samples placed back to back were
      employed. Experiments were performed at the 4.5MV Van de Graaff accelerator of
      Peking University. Neutrons were produced through the D(d, n)(3)He reaction with
      a deuterium gas target. Absolute neutron flux was determined by a small (238)U
      fission chamber. Present cross-section data are compared with existing results of
      evaluations and measurements.

PMID- 18707896
TI  - Percoll-purified and photosynthetically active chloroplasts from Arabidopsis
      thaliana leaves.
AB  - The availability of the complete genome sequence of Arabidopsis thaliana and of
      large collections of insertion mutants paved the way for systematic studies of
      gene functions in this organism, thus requiring adapting biochemical and
      physiological tools to this model plant. For physiological analysis of
      photosynthesis, methods combining high level of chloroplast purity and
      preservation of the photosynthetic activity were missing. Here, we describe a
      rapid method (less than 1h) to obtain Percoll-purified and photosynthetically
      active chloroplasts from Arabidopsis leaves retaining almost 90% of the Vmax of
      photosynthesis measured in the starting leaves from plants grown under a light
      intensity of 150mumolphotonm(-2)s(-1) and 80% of their initial photosynthetic
      rate after 3h of storage.

PMID- 18707897
TI  - Effect of interleukin-2 on synthesis of B cell activating factor belonging to the
      tumor necrosis factor family (BAFF) in human peripheral blood mononuclear cells.
AB  - B cell activating factor belonging to the tumor necrosis factor family (BAFF) is
      a cytokine, indispensable for B cell survival, maturation, and activation. Over
      expression of BAFF leads to lupus like disease in mice and the serum level of
      BAFF is elevated in human lupus. However, little is known about BAFF synthesis
      and its regulation. In this study, we examined the effects of a series of
      inflammatory cytokines on BAFF production in human peripheral blood mononuclear
      cells (PBMCs) in vitro. We found interleukin-2 (IL-2) strongly and dose
      dependently stimulated BAFF synthesis in PBMCs, and an anti-IL-2 antibody
      neutralized the effect. Furthermore, T and NK cells produced BAFF with IL-2
      stimulation. From these observations, IL-2 is one of the regulatory cytokines
      having a positive effect on BAFF synthesis in human peripheral T and NK cells.
      Persistent over-production of IL-2 might lead to up-regulation of BAFF synthesis
      in PBMCs in pathological conditions such as lupus.

PMID- 18707898
TI  - Roles of ubiquitination in pattern-recognition receptors and type I interferon
      receptor signaling.
AB  - Post-translational protein modifications are involved in all functions of living
      cells. This includes the ability of cells to recognize pathogens and regulate
      genes involved in their clearance, a concept known as innate immunity. While
      phosphorylation mechanisms play essential roles in regulating different aspects
      of the innate immune response, ubiquitination is now recognized as another post
      translational modification that works in parallel with phosphorylation to
      orchestrate the final proper innate immune response against invading pathogens.
      More precisely, this review will discuss the most recent advances that address
      the role of ubiquitination in pattern-recognition receptors and type I interferon
      receptor signaling.

PMID- 18707899
TI  - Involvement of ERK-1/2 in IL-21-induced cytokine production in leukemia cells and
      human monocytes.
AB  - Cytokines play an important role in the immune system, and abnormalities in their
      production have been found in many human diseases. Interleukin-21 (IL-21), a type
      I cytokine produced by activated T cells, has diverse effects on the immune
      system, but its ability to induce production of other cytokines is not well
      delineated. Furthermore, the signaling pathway underlying its action is poorly
      understood. Here, we have evaluated IL-21-induced cytokine production in human
      monocytes and U937 leukemia cells. We found that IL-21 induces upregulation of a
      variety of cytokines from multiple cytokine families. We also found that IL-21
      triggers rapid activation of ERK1/2. Neutralizing antibody to the IL-21R
      prevented both IL-21-induced cytokine production and IL-21-induced activation of
      ERK1/2. Inhibition of ERK1/2 activity by the ERK-selective inhibitor U0126
      reverses the ability of IL-21 to upregulate cytokine production, suggesting that
      IL-21-induced cytokine production is dependent on ERK1/2 activation.

PMID- 18707900
TI  - Comparison of LC and LC/MS methods for quantifying N-glycosylation in recombinant
      IgGs.
AB  - High-performance liquid chromatography (LC) and liquid
      chromatography/electrospray ionization time-of-flight mass spectrometry (LC/ESI
      MS) methods with various sample preparation schemes were compared for their
      ability to identify and quantify glycoforms in two different production lots of a
      recombinant monoclonal IgG1 antibody. IgG1s contain a conserved N-glycosylation
      site in the fragment crystallizable (Fc) subunit. Six methods were compared: (1)
      LC/ESI-MS analysis of intact IgG, (2) LC/ESI-MS analysis of the Fc fragment
      produced by limited proteolysis with Lys-C, (3) LC/ESI-MS analysis of the IgG
      heavy chain produced by reduction, (4) LC/ESI-MS analysis of Fc/2 fragment
      produced by limited proteolysis and reduction, (5) LC/MS analysis of the
      glycosylated tryptic fragment (293EEQYNSTYR301) using extracted ion
      chromatograms, and (6) normal phase HPLC analysis of N-glycans cleaved from the
      IgG using PNGase F. The results suggest that MS quantitation based on the
      analysis of Fc/2 (4) is accurate and gives results that are comparable to normal
      phase HPLC analysis of N-glycans (6).

PMID- 18707902
TI  - Relationships between ball velocity and throwing mechanics in collegiate baseball
      pitchers.
AB  - Although ball speed is considered a measure of success in baseball pitching,
      little is known about the relationship between ball velocity and pitching
      mechanics. Investigation of this relationship has been limited, and the studies
      carried out have varied in methodology. Three-dimensional, high-speed (240 Hz)
      video data were collected on fastballs from 54 collegiate baseball pitchers.
      Kinematic parameters related to pitching mechanics and resultant kinetics on the
      throwing shoulder and elbow were calculated. Multiple linear regression analysis
      was used to relate ball velocity and pitching mechanics. Ball velocity averaged
      35 m/sec (79 mph) for the 54 college pitchers. Nearly 70% of the variability in
      ball speed can be explained by a combination of 10 parameters related to pitching
      mechanics. Body mass and 9 temporal and kinematic parameters related to pitching
      mechanics combine to account for 68% of the variance in ball velocity for a
      collegiate population of athletes. These variables can be manipulated via
      mechanical changes and sport-specific training to affect ball velocity. The
      results of the study can be used to increase ball velocity while at the same time
      minimizing stresses on the throwing arm elbow and shoulder. Improved training
      programs can begin to be developed based on these data.

PMID- 18707901
TI  - Quantifying protein interface footprinting by hydroxyl radical oxidation and
      molecular dynamics simulation: application to galectin-1.
AB  - Biomolecular surface mapping methods offer an important alternative method for
      characterizing protein-protein and protein-ligand interactions in cases in which
      it is not possible to determine high-resolution three-dimensional (3D) structures
      of complexes. Hydroxyl radical footprinting offers a significant advance in
      footprint resolution compared with traditional chemical derivatization. Here we
      present results of footprinting performed with hydroxyl radicals generated on the
      nanosecond time scale by laser-induced photodissociation of hydrogen peroxide. We
      applied this emerging method to a carbohydrate-binding protein, galectin-1. Since
      galectin-1 occurs as a homodimer, footprinting was employed to characterize the
      interface of the monomeric subunits. Efficient analysis of the mass spectrometry
      data for the oxidized protein was achieved with the recently developed ByOnic
      (Palo Alto, CA) software that was altered to handle the large number of
      modifications arising from side-chain oxidation. Quantification of the level of
      oxidation has been achieved by employing spectral intensities for all of the
      observed oxidation states on a per-residue basis. The level of accuracy
      achievable from spectral intensities was determined by examination of mixtures of
      synthetic peptides related to those present after oxidation and tryptic digestion
      of galectin-1. A direct relationship between side-chain solvent accessibility and
      level of oxidation emerged, which enabled the prediction of the level of
      oxidation given the 3D structure of the protein. The precision of this
      relationship was enhanced through the use of average solvent accessibilities
      computed from 10 ns molecular dynamics simulations of the protein.

PMID- 18707903
TI  - Osteochondritis dissecans of the radial head: a case report.

PMID- 18707904
TI  - The management of cancer-related breakthrough pain: recommendations of a task
      group of the Science Committee of the Association for Palliative Medicine of
      Great Britain and Ireland.
AB  - A task group of the Science Committee of the Association for Palliative Medicine
      of Great Britain and Ireland (APM) was convened to produce some up-to-date,
      evidence-based, practical, clinical guidelines on the management of cancer
      related breakthrough pain in adults. On the basis of a review of the literature,
      the task group was unable to make recommendations about any individual
      interventions, but was able to make a series of 12 recommendations about certain
      generic strategies. However, most of the aforementioned recommendations are based
      on limited evidence (i.e., case series, expert opinion). The task group also
      proposed a definition of breakthrough pain, and some diagnostic criteria for
      breakthrough pain.

PMID- 18707905
TI  - High-resolution 14N-edited 1H-13C correlation NMR experiment to study biological
      solids.
AB  - It was recently shown that nuclear magnetic resonance (NMR) spectra of nitrogen
      14 (spin I=1) can be obtained by indirect detection via spin S=1/2 nuclei in
      powders spinning at the magic angle. An increased number of solid-state NMR
      methods are now available to tailor sequences for specific purposes, e.g., hetero
      nuclear dipolar recoupling or homo-nuclear dipolar decoupling schemes. Here, we
      combine the latest recoupling and decoupling techniques to obtain high-resolution
      (1)H-(13)C through-space correlation spectra, where only the correlation peaks of
      those carbons close to nitrogen nuclei are observed. The experiment is
      demonstrated on a (13)C enriched l-histidine. HCl x H(2)O powder sample.

PMID- 18707906
TI  - Granulomatous inflammation in juvenile idiopathic arthritis-associated uveitis.
AB  - PURPOSE: The uveitis that is associated with juvenile idiopathic arthritis (JIA)
      has typically been described as nongranulomatous. This study reports the
      prevalence of granulomatous disease in a population with JIA-associated uveitis.
      METHODS: We conducted a retrospective analysis of all patients with JIA
      associated uveitis seen between 1973 and 2006 at a hospital-based uveitis
      service. Patients with uveitis were included if they were diagnosed with JIA by a
      specialist and experienced at least 6 weeks of arthritis starting before the age
      of 16 years. Granulomatous disease was defined as Busacca or angle nodules,
      mutton-fat keratic precipitates (KP), or hyalinized "ghost" KPs. Statistical
      tests were performed to seek associations between granulomatous disease and
      various clinical factors. RESULTS: Seventy-one patients with JIA-associated
      uveitis were included. Granulomatous uveitis was observed in 28% of the
      population, with 7% exhibiting mutton-fat KP, and 21% "ghost" KP. There was no
      association between the presence of granulomatous disease and age of arthritis
      onset, age of uveitis onset, sex, antinuclear antibody status, or whether the
      arthritis was pauciarticular or polyarticular. In this population, 67% of black
      patients had granulomatous disease compared with 25% of nonblack patients (p <
      0.05), and 24% of white patients showed granulomatous disease compared with 56%
      of nonwhite patients (p = 0.11). CONCLUSIONS: Granulomatous disease is more
      common in JIA-associated uveitis than previously thought and may be more common
      in black patients. Although it is necessary to exclude other forms of
      granulomatous uveitis, such as sarcoidosis, the presence of granulomatous uveitis
      is not inconsistent with a diagnosis of JIA-associated uveitis.

PMID- 18707907
TI  - Globotriaosylceramide induces oxidative stress and up-regulates cell adhesion
      molecule expression in Fabry disease endothelial cells.
AB  - Fabry disease, an X-linked systemic vasculopathy, is caused by a deficiency of
      alpha-galactosidase A resulting in globotriaosylceramide (Gb(3)) storage in
      cells. The pathogenic role of Gb(3) in the disease is not known. Based on
      previous work, we tested the hypothesis that accumulation of Gb(3) in the
      vascular endothelium of Fabry disease is associated with increased production of
      reactive oxygen species (ROS) and increased expression of cell adhesion
      molecules. Gb(3)-loading resulted in increased intracellular ROS production in
      cultured vascular endothelial cells in a dose-dependent manner. Increased Gb(3)
      also induced expression of intercellular adhesion molecule-1, vascular cell
      adhesion molecule-1, and E-selectin. Reduction of endogenous Gb(3) by treatment
      of the cells with an inhibitor of glycosphingolipid synthase or alpha
      galactosidase A led to decreased expression of adhesion molecules. Plasma from
      Fabry patients significantly increased ROS generation in endothelial cells when
      compared with plasma from non-Fabry controls. This effect was not influenced by
      reduction of intracellular Gb(3). This study provided direct evidence that excess
      intracellular Gb(3) induces oxidative stress and up-regulates the expression of
      cellular adhesion molecules in vascular endothelial cells. In addition, other
      factors in patient's plasma may also contribute to oxidative stress in Fabry
      vascular endothelial cells.

PMID- 18707908
TI  - Radiographic evaluation of bones and joints in mucopolysaccharidosis I and VII
      dogs after neonatal gene therapy.
AB  - Mucopolysaccharidosis I (MPS I) and MPS VII are due to deficient activity of the
      glycosaminoglycan-degrading lysosomal enzymes alpha-L-iduronidase and beta
      glucuronidase, respectively, and result in abnormal bones and joints. Here, the
      severity of skeletal disease in MPS I and MPS VII dogs and the effects of
      neonatal gene therapy were evaluated. For untreated MPS VII dogs, the lengths of
      the second cervical vertebrae (C2) and the femur were only 56% and 84% of normal,
      respectively, and bone dysplasia and articular erosions, and joint subluxation
      were severe. Previously, we reported that neonatal intravenous injection of a
      retroviral vector (RV) with the appropriate gene resulted in expression in liver
      and blood cells, and high serum enzyme activity. In this study, we demonstrate
      that C2 and femurs of RV-treated MPS VII dogs were longer at 82% and 101% of
      normal, respectively, and there were partial improvements of qualitative
      abnormalities. For untreated MPS I dogs, the lengths of C2 and femurs (91% and
      96% of normal, respectively) were not significantly different from normal dogs.
      Qualitative changes in MPS I bones and joints were generally modest and were
      partially improved with RV treatment, although cervical spine disease was severe
      and was difficult to correct with gene therapy in both models. The greater
      severity of skeletal disease in MPS VII than in MPS I dogs may reflect
      accumulation of chondroitin sulfate in cartilage in MPS VII, or could relate to
      the specific mutations. Neonatal RV-mediated gene therapy ameliorates, but does
      not prevent, skeletal disease in MPS I and MPS VII dogs.

PMID- 18707909
TI  - Non-typhoidal Salmonella septic arthritis in an immunocompetent child with a
      pharyngeal streptococcal infection.
AB  - We report the case of an immunocompetent child who showed monoarticular arthritis
      and fever, preceded by pharyngitis and arthralgias. Because group A beta
      hemolytic Streptococcus had been detected in the pharyngeal swab, erythromycin
      was given on admission. However, based on ultrasound examination, therapy with
      ceftriaxone and joint fluid drainage were promptly performed, and a rapid and
      full recovery followed. Meanwhile, Salmonella enterica infection was revealed in
      blood and joint fluid. Our case suggests that septic arthritis caused by a non
      typhoidal Salmonella infection may occur without gastrointestinal manifestations
      and concomitantly with a pharyngeal streptococcal infection.

PMID- 18707910
TI  - Bone mineral density of young boy soccer players at different pubertal stages:
      relationships with hormonal concentration.
AB  - OBJECTIVES: To examine the effects of soccer in relation with the hormonal
      concentration, on the bone mass of young Tunisian players at different pubertal
      stages. METHODS: Two groups of 152 young boys (age: 13.3+/-0.9 years)
      participated in this study: (1) 91 soccer players, and (2) 61 non-athletic boys
      used as control subjects. The bone mineral density (BMD) and the bone mineral
      content (BMC) were measured by dual-energy X-ray absorptiometry (DXA). Pubertal
      stages were assessed, and serum concentrations of insulin-like growth factor-1
      (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), growth hormone
      (GH) and the total testosterone were measured. RESULTS: The BMD and BMC for whole
      body, lumbar spine, femoral neck, pelvis and lower limbs were higher in soccer
      players than in controls (p<0.001). In early puberty, the soccer players also
      exhibited significantly greater BMD and BMC in the whole body and in weight
      bearing bones compared with the controls (p<0.001). However, there was no
      intersubject variability due to puberty in either BMD or BMC. The pubescent
      soccer players had significantly higher hormonal concentrations of IGF-1 and
      IGFBP-3 than their counterpart controls (p<0.05). Moreover, the whole body BMD
      was significantly (p<0.001) correlated with GH, IGF-1 and IGFBP-3 but not with
      the testosterone concentrations. CONCLUSION: The soccer participation of boys is
      generally associated with the improvement of their bone mass which is mainly
      marked at early and late puberty. The relationships between somatotropic axis
      hormones and BMD of the players may be linked to the parallel development of
      these two parameters during puberty.

PMID- 18707911
TI  - [Environmental pollutants in maternal milk and cryptorchidism].
AB  - OBJECTIVE: Numerous maternal lipophilic compounds are eliminated into milk during
      lactation, their concentrations reflecting fetal in utero exposure. Some of them
      are endocrine disruptors. Their role in the occurrence of genital malformation,
      dysfunction or cancer has been suggested. We wanted to study the exposure of our
      population and its potential association with cryptorchidism, as few clinical
      studies are available. PATIENTS AND METHODS: Over three years, we screened for
      cryptorchidism all boys born alive at or above 34 weeks of gestational age, in
      two maternity wards (CHU Nice, CHG Grasse). Cryptorchid boys were matched with
      two controls. Nursing mothers provided a colostrum sample that was screened for
      15 compounds known for their antiandrogenic and/or anti estrogenic properties,
      including dichloro-diphenyl-trichloro-ethylene (DDE), polychlorinated biphenyls
      (PCBs), dibutylphthalate (DBP) (& metabolite monobutylphthalate-mBP) and
      hexachlorobenzene (HCB). RESULTS: Out of 6246 boys, 102 were cryptorchid (1.6%).
      All available colostrums (56 for cryptorchid and 69 for controls) were
      contaminated. Median concentrations of DDE, PCBs, HCB and phthalates were higher
      though not significantly in cryptorchid versus controls. Cryptorchid boys were
      more likely to be classified in the most contaminated groups for DDE and
      SigmaPCBs, with a trend for mBP. Odds ratio (OR) for cryptorchidism was increased
      for the highest score of SigmaPCB, with a trend only for DDE versus the lowest
      score of those components. Our results are similar to those of a Scandinavian
      study with comparable design. DISCUSSION AND CONCLUSIONS: Our results show the
      universal contamination of milk with endocrine disruptors in our area, and
      support the association between congenital cryptorchidism and fetal exposure to
      PCBs and possibly DDE, alone or in association with other chemicals.

PMID- 18707912
TI  - [Bladder endometriosis and barrenness: diagnostic and treatment strategy].
AB  - Deep infiltrating endometriosis is a well-known female disease responsible for
      chronic pelvic pain, urinary dysfunction, infertility, and altered quality of
      life. Endometriosis and infertility are complex entities and the optimal choice
      of management of both of them remains obscure. Mechanism of development of the
      disease has to be understood to optimize patients care. The link between
      barrenness and endometriosis is well known, but there is no direct link between
      bladder lesion and infertility. Bladder endometriosis is a deeply infiltrating
      endometriosis lesion. Its management is first diagnostic and then remedial. In
      case of ineffectiveness of medical strategy, surgical treatment is indicated.
      However, for patient suffering from symptomatic isolated bladder endometriosis,
      surgical management can be offered in first intention. Isolated bladder injuries
      due to endometriosis are mostly treated by conservative laparoscopic surgery,
      after a complete evaluation of endometriosis disease and barrenness by clinical
      exam and imaging techniques.

PMID- 18707914
TI  - Influence of adding salt on ultrasonic atomization in an ethanol-water solution.
AB  - Ethanol was enriched by ultrasonic atomization. Enrichment ratios were increased
      by adding salt to the ethanol solution. Different enrichment ratios were observed
      for different types of salts in a range of low ethanol concentrations. The
      enrichment ratio was significantly improved by adding K(2)CO(3) or
      (NH(4))(2)SO(4). It is concluded that this is due to enhanced interfacial
      adsorption of the ethanol. Addition of Na(2)CO(3) to the ethanol solution also
      enhanced the interfacial adsorption of the ethanol, but the effect was relatively
      small. Addition of NaCl to the ethanol solution did not enhance the interfacial
      adsorption of the ethanol.

PMID- 18707913
TI  - [Effect of women's weight on the success rate of in vitro fertilization].
AB  - OBJECTIVE: To examine the effect of women's weight on the success rate of in
      vitro fertilization. PATIENTS AND METHODS: Single centre retrospective study of a
      continuous series of 846 patients who underwent 1444 in vitro fertilization or
      ICSI cycles. The outcomes of each cycle was analysed as a function of the woman's
      body mass index (BMI). Three groups were defined: (1) underweight (BMI<18 kg/m2,
      n=68 cycles, 43 women), (2) normal BMI (18 < or =BMI<25, n=1045 cycles, 607
      women), (3) overweight or obese women (IMC > or =25, n=331 cycles, 196 women).
      MAIN OUTCOME MEASUREMENT: Live birth rate per cycle. RESULTS: In group 3, the
      live birth rate per cycle (10,6% [95% confidence interval: 7,3-13,9]) was
      significantly lower than in group 2 (16,6% [14,3-18,8]). There was a non
      significant trend towards a decreased live birth rate in group I (11,8% [4,1
      19,4]). In group 3, the cancellation rate (30,8% [25,8-35,8]) was significantly
      greater than in group 2 (19,6% [17,2-22]), the pregnancy per oocyte pick-up rate
      was lower (19,9% versus 24,6%) and the early miscarriage rate was increased
      (26,9% versus 15,7%) without reaching statistical significance. DISCUSSION AND
      CONCLUSION: The live birth rate was decreased among overweight or obese women.
      This could be mediated by impairment of response to ovarian stimulation, oocyte
      quality, or implantation abnomalies.

PMID- 18707915
TI  - Flow through a defective mechanical heart valve: a steady flow analysis.
AB  - Approximately 250,000 valve replacement operations occur annually around the
      world and more than two thirds of these operations use mechanical heart valves
      (MHV). These valves are subject to complications such: pannus and/or thrombus
      formation. Another potential complication is a malfunction in one of the valve
      leaflets. Although the occurrence of such malfunctions is low, they are life
      threatening events that require emergency surgery. It is, therefore, important to
      develop parameters that will allow an early non-invasive diagnosis of such valve
      malfunction. In the present study, we performed numerical simulations of the flow
      through a defective mechanical valve under several flow and malfunction severity
      conditions. Our results show that the flow upstream and downstream of the
      defective valve is highly influenced by malfunction severity and this resulted in
      a misleading improvement in the correlation between simulated Doppler
      echocardiographic and catheter transvalvular pressure gradients. In this study,
      we were also able to propose and test two potential non-invasive parameters,
      using Doppler echocardiography and phase contrast magnetic resonance imaging, for
      an early detection of mechanical heart valve malfunction. Finally, we showed that
      valve malfunction has a significant impact on platelet activation and therefore
      on thrombus formation.

PMID- 18707916
TI  - Bilateral basal ganglia lesions of primary Sjogren syndrome presenting with
      generalized chorea.

PMID- 18707917
TI  - Airbag-induced corneal flap.
AB  - PURPOSE: To describe a case of airbag-induced corneal flap in a previously normal
      cornea. METHODS: Case report. RESULTS: A 27-year-old woman presented with
      complete loss of vision in her left eye following a road traffic accident which
      involved airbag deployment. There was no previous ocular history. Examination
      revealed a large corneal flap of 6mm in diameter, extending to the depth of
      anterior stroma. This was accompanied by a traumatic optic neuropathy. One month
      follow-up revealed complete reattachment of the corneal flap. CONCLUSIONS: This
      is the first reported case of a corneal flap induced by airbag deployment in a
      cornea with previously normal architecture.

PMID- 18707918
TI  - HCV quasispecies evolution during treatment with interferon alfa-2b and ribavirin
      in two children coinfected with HCV and HIV-1.
AB  - Two children who acquired hepatitis C virus (HCV) and human immunodeficiency
      virus type 1 (HIV-1) infection by mother-to-child transmission were monitored
      during interferon alfa-2b and ribavirin treatment. In Patient C1, CD4(+) T cell
      counts were within normal range and HIV-1 viral load was undetectable. HCV viral
      load declined slightly following treatment initiation while novel variants
      rapidly emerged, indicative of quasispecies diversification. In Patient C2,
      CD4(+) T cell counts were low and HIV-1 replication was not fully controlled by
      antiretroviral therapy. HCV viral load rose during treatment and a striking
      conservation of the variant spectrum was observed. In both cases, there was no
      decline in quasispecies complexity following treatment initiation and sustained
      virological response was not achieved. These results suggest that reduction in
      quasispecies complexity, which is observed in adult responders following
      interferon treatment, may be mechanistically unrelated with evolution of the
      variant profile and/or selective pressure exerted on HCV.

PMID- 18707919
TI  - Exploiting host compensatory responses: the 'must' of manipulation?
AB  - Parasite-induced alterations of the host phenotype have been reported in many
      systems. These changes are traditionally categorized into three kinds of
      phenomena: secondary outcomes of infection with no adaptive value, host
      adaptations that reduce the detrimental consequences of infection and parasitic
      adaptations that facilitate transmission. However, this categorization is a
      simple view, and host modifications should be considered as co-evolved traits,
      rather than a total takeover. Here, we present a novel scenario of manipulation,
      which has considerable potential to resolve issues that are specific to the
      evolution of behavioural alterations induced by parasites. It is proposed that
      certain parasites affect fitness-related traits in their hosts to trigger host
      compensatory responses because these responses can meet the transmission
      objectives of parasites.

PMID- 18707920
TI  - The feasibility of introducing an evidence based practice cycle into a clinical
      area: An evaluation of process and outcome.
AB  - The aim was to examine the feasibility of introducing an evidence based practice
      (EBP) cycle into a practice area within an undergraduate pre-registration
      programme. The cycle involved four meetings over five weeks on a cardiac
      intensive care unit. Three 3rd year adult branch nursing students participated
      with their mentors. A web page for the project was developed to support the
      process. Evaluation focused on changes in EBP knowledge and skills and issues
      around implementation and perceived value of the EBP cycle. The findings showed
      that the EBP cycle was straight forward to set up and was recognised as being of
      value by both students and mentors. The students demonstrated modest improvements
      in EBP knowledge and skills. The main problems were lack of time and difficulties
      in accessing on-line resources.

PMID- 18707922
TI  - In vitro expanded human invariant natural killer T-cells promote functional
      activity of natural killer cells.
AB  - Invariant natural killer T (iNKT) cells play a pivotal role in cancer immunity
      through trans-activation of effector cells via swift cytokine secretion. In mice,
      iNKT cell activation by alpha-galactosylceramide (alpha-GC) induces potent NK
      cell-mediated anti-tumour effects. Here we investigated whether human iNKT cells
      could enhance NK cell functional activity in vitro. iNKT cell activation by alpha
      GC treatment of peripheral blood mononuclear cells (PBMC) was not sufficient to
      enhance NK cell effector functions. However, addition of in vitro expanded iNKT
      cells to PBMC enhanced NK cell-mediated cytotoxicity in an alpha-GC-dependent
      manner. NK cell activation by iNKT cells was primarily mediated by soluble
      factors, and could be enhanced by the NK cell activating cytokine IL-21. These
      results suggest that adoptive transfer of ex vivo expanded iNKT cells will
      enhance NK cell function and is expected to enhance the efficacy of cancer
      immunotherapy, particularly in combination with IL-21 and alpha-GC.

PMID- 18707921
TI  - Effect of thrombocytapheresis on blood rheology in healthy donors: role of nitric
      oxide.
AB  - Platelet transfusions are increasingly being used to treat thrombocytopenic
      conditions. Because of anticoagulation, changes in blood composition and
      extracorporeal circulation, donor apheresis may cause alterations in
      hemorheology. This study aimed at investigating the effects of
      thrombocytapheresis on donor blood rheology. The effect of nitric oxide (NO) on
      donor red blood cell (RBC) deformability after thrombocytapheresis was also
      studied. Platelets were collected by a Haemonetics MCS 3p cell seperator. Blood
      samples were obtained before and 15 min after thrombocytapheresis. RBC
      deformability and aggregation were measured using an ektacytometer, whole blood
      viscosity (WBV) was determined with a cone-plate rotational viscometer. Donor
      RBCs were shown to be less deformable at all stress levels except 0.30 Pa after
      thrombocytapheresis and NO donor sodium nitroprusside (SNP, 10(-6) M) reversed
      the reduced deformability caused by thrombocytapheresis. It was observed that
      donor apheresis induces a decrement in RBC aggregation and WBV measured at
      standard hematocrit (Hct). No significant alterations were observed in WBV values
      determined at native Hct values. Thrombocytapheresis also resulted in a decrement
      in fibrinogen, total protein, cholesterol and albumin levels whereas Hct was
      found to be increased and serum glucose, triglyceride, hemoglobin levels
      unaltered after apheresis. These results suggest that, thrombocytapheresis causes
      alterations in hemorheological parameters and hence in the perfusion of the
      microvasculature of the donors and NO appears to have a protective effect on the
      impairment observed in RBC deformability.

PMID- 18707923
TI  - Expression of PD-1 is up-regulated in CD4+CD25+ FoxP3+ regulatory T cell of non
      responders after hepatitis B surface antigen vaccine immunization.

PMID- 18707924
TI  - The syndrome of inappropriate anti-diuretic hormone secretion concurrent with an
      acute exacerbation of cystic fibrosis.
AB  - Acute exacerbations of cystic fibrosis (CF) can be associated with dehydration,
      hyponatraemia and hypochloraemia. The syndrome of inappropriate anti-diuretic
      hormone secretion (SIADH) has also been described in CF patients in the setting
      of hyponatraemia, but may be under-recognised. Diagnosing SIADH has therapeutic
      implications as it necessitates fluid and water restriction rather than fluid
      resuscitation. We report the case of an acute pulmonary exacerbation of CF in
      which features of SIADH are demonstrated.

PMID- 18707925
TI  - Determination of rimonabant in human plasma and hair by liquid chromatography
      mass spectrometry.
AB  - Rimonabant is the first therapeutically relevant cannabinoid antagonist, licensed
      in Europe for treatment of obesity when a risk factor is associated. The
      objective of this study was to develop and validate a method for measurement of
      rimonabant in human plasma and hair using liquid chromatography coupled to mass
      spectrometry (LC-MS/MS). Rimonabant and AM-251 (internal standard) were extracted
      from 50 microL of plasma or 10 mg of hair using diethylether. Chromatography was
      performed on a 150 mm x 2.1 mm C18 column using a mobile phase constituted of
      formate buffer/acetonitrile. Rimonabant was ionized by electrospray in positive
      mode, followed by detection with mass spectrometry. Data were collected either in
      full-scan MS or in full-scan MS/MS mode, selecting the ion m/z 463.1 for
      rimonabant and m/z 555.1 for IS. The most intense product ion of rimonabant (m/z
      380.9) and IS (m/z 472.8) were used for quantification. Calibration curves
      covered a range from 2.5 (lower limit of quantification) to 1000.0 ng/mL (upper
      limit of quantification) in plasma and from 2.5 to 1000.0 pg/mg in hair.
      Validation results demonstrated that rimonabant could be accurately and precisely
      quantified in both matrixes: accuracy and precision were within 85-115% and
      within 15% of standard deviation, respectively. Stability studies in plasma
      showed that rimonabant was stable during the assay procedure, but a 30% decrease
      was observed for one concentration after 3 weeks at -20 degrees C. This simple
      and robust LC-MS/MS method can be used for measuring rimonabant concentrations in
      human plasma and hair either in clinical or in forensic toxicology.

PMID- 18707927
TI  - Mandibular condyle and infratemporal fossa reconstruction using vascularised
      iliac crest and vascularised calvarial bone graft.

PMID- 18707926
TI  - Electrochemical stability and corrosion resistance of Ti-Mo alloys for biomedical
      applications.
AB  - Electrochemical behavior of pure Ti and Ti-Mo alloys (6-20wt.% Mo) was
      investigated as a function of immersion time in electrolyte simulating
      physiological media. Open-circuit potential values indicated that all Ti-Mo
      alloys studied and pure Ti undergo spontaneous passivation due to spontaneously
      formed oxide film passivating the metallic surface, in the chloride-containing
      solution. It also indicated that the addition of Mo to pure Ti up to 15wt.% seems
      to improve the protection characteristics of its spontaneous oxides.
      Electrochemical impedance spectroscopy (EIS) studies showed high impedance values
      for all samples, increasing with immersion time, indicating an improvement in
      corrosion resistance of the spontaneous oxide film. The fit obtained suggests a
      single passive film present on the metals' surface, improving their resistance
      with immersion time, presenting the highest values to Ti-15Mo alloy.
      Potentiodynamic polarization showed a typical valve-metal behavior, with anodic
      formation of barrier-type oxide films, without pitting corrosion, even in
      chloride-containing solution. In all cases, the passive current values were quite
      small, and decrease after 360h of immersion. All these electrochemical results
      suggest that the Ti-15Mo alloy is a promising material for orthopedic devices,
      since electrochemical stability is directly associated with biocompatibility and
      is a necessary condition for applying a material as biomaterial.

PMID- 18707928
TI  - Partner support in the childbearing period -- a follow up study.
AB  - BACKGROUND: Social support is important during pregnancy and childbirth and the
      partner is usually the main source of support. Lack of partner support is
      associated with less emotional well-being and discontinuation of breastfeeding.
      RESEARCH PROBLEM: The purpose of the study was to investigate the proportion of
      women dissatisfied with partner support in early pregnancy, and to identify risk
      factors associated with dissatisfaction through a follow up 2 months and 1 year
      after childbirth. PARTICIPANTS AND METHODS: A national cohort of 2430 Swedish
      speaking women recruited in early pregnancy and followed up 2 months and 1 year
      postpartum. Data were collected by means of three postal questionnaires. RESULTS:
      Five percent of women were dissatisfied with partner support in early pregnancy.
      Women dissatisfied with partner support were more likely to be multiparas, not
      living with their partner in early pregnancy and to report unfavorable timing of
      pregnancy. They experienced more physical symptoms, and less emotional well-being
      in terms of more depressive symptoms, more major worries and a lower sense of
      coherence. One year after childbirth a higher rate of divorces and disappointment
      with the partner's participation in childcare and household chores and
      understanding from partner was found in women being dissatisfied in early
      pregnancy. DISCUSSION AND CONCLUSIONS: This study shows that it might be possible
      to identify women who are lacking partner support already in early pregnancy.
      Women's social network and their support from partner should be investigated by
      health care providers and women in need of additional support should be refereed
      to available community resources.

PMID- 18707929
TI  - [Revisiting pharmacological actions of antidepressants: the example of
      escitalopram].

PMID- 18707931
TI  - [From one indication to another: the benefit of longitudinal studies].

PMID- 18707930
TI  - [The place of escitalopram in the severe depressive episodes].

PMID- 18707932
TI  - [On bipolar disorder].

PMID- 18707933
TI  - [Genetics of bipolar disorder and environment].

PMID- 18707934
TI  - [From psychotic to bipolar disorders].

PMID- 18707935
TI  - [Bipolar and other affective disorders].

PMID- 18707936
TI  - [Comorbid addictions in bipolar disorder].

PMID- 18707937
TI  - [Bipolar disorder and somatic comorbidity].

PMID- 18707938
TI  - [Cerebral images in bipolar disorder].

PMID- 18707939
TI  - [Guidelines and consensus conferences on the treatment of bipolar disorder].

PMID- 18707940
TI  - [Functional behavior and psychosocial therapy in bipolar disorder].

PMID- 18707941
TI  - Delirium, Cinderella no more...?

PMID- 18707942
TI  - Defining delirium for the International Classification of Diseases, 11th
      Revision.
AB  - OBJECTIVE: The development of ICD-11 provides an opportunity to update the
      description of delirium according to emerging data that have added to our
      understanding of this complex neuropsychiatric syndrome. METHOD: Synthetic
      article based on published work considered by the authors to be relevant to the
      definition of delirium. RESULTS: The current DSM-IV definition of delirium is
      preferred to the ICD-10 because of its greater inclusivity. Evidence does not
      support major changes in the principal components of present definitions but a
      number of key issues for the updated definition were identified. These include
      better account of non-cognitive features, more guidance for rating contextual
      diagnostic items, clearer definition regarding the interface with dementia, and
      accounting for illness severity, clinical subtypes and course. CONCLUSION:
      Development of the ICD definition of delirium can allow for more targeted
      research and clinical effort.

PMID- 18707943
TI  - Delirium phenomenology: what can we learn from the symptoms of delirium?
AB  - OBJECTIVES: This review focuses on phenomenological studies of delirium,
      including subsyndromal and prodromal concepts, and their relevance to other
      elements of clinical profile. METHODS: A Medline search using the keywords
      delirium, phenomenology, and symptoms for new data articles published in English
      between 1998 and 2008 was utilized. The search was supplemented by additional
      material not identified by Medline but known to the authors. RESULTS:
      Understanding of prodromal and subsyndromal concepts is still in its infancy. The
      characteristic profile can differentiate delirium from other neuropsychiatric
      disorders. Clinical (motoric) subtyping holds potential but more consistent
      methods are needed. Studies are almost entirely cross-sectional in design and
      generally lack comprehensive symptom assessment. Multiple assessment tools are
      available but are oriented towards hyperactive features and few have demonstrated
      ability to distinguish delirium from dementia. There is insufficient evidence
      linking specific phenomenology with etiology, pathophysiology, management,
      course, and outcome. CONCLUSIONS: Despite the major advancements of the past
      decade in many aspects of delirium research, further phenomenological work is
      crucial to targeting studies of causation, pathophysiology, treatment, and
      prognosis. We identified eight key areas for future studies.

PMID- 18707944
TI  - The delirium experience: a review.
AB  - While the adverse medical complications and consequences of delirium has been
      well studied, the same is not true of the psychological morbidity associated with
      the condition. A better understanding of what it is like to be delirious has the
      potential to improve recognition, management and treatment of delirium. This
      article examines the literature relating to the experience of delirium from the
      perspective of patients, families, and staff. Finally, suggestions for further
      work that might advance might advance our understanding of these issues are
      outlined.

PMID- 18707946
TI  - Neuroimaging studies of delirium: a systematic review.
AB  - OBJECTIVE: Neuroimaging offers clear potential in developing a better
      understanding of the pathophysiology of delirium. We performed a systematic
      review of structural and functional neuroimaging findings in delirium. The aims
      were to categorize and summarize the existing literature, and to determine
      whether this literature provides conclusive information on structural or
      functional brain predictors, correlates, or consequences of delirium. METHODS:
      Studies were identified by comprehensive textword and MeSH-based electronic
      searches of MEDLINE, EMBASE, and Evidence-Based Medicine reviews, combining
      multiple terms for neuroimaging, brain structure, and delirium. RESULTS: Twelve
      studies met the inclusion criteria. There were a total of 194 patients with
      delirium and 570 controls. Patient age, population, comorbidities, and identified
      precipitating factors were heterogeneous. Of the 10 structural studies, 3 studies
      used computed tomography (CT), 3 studies used magnetic resonance imaging (MRI),
      and 4 studies used a mixture of CT and MRI. One functional study used xenon CT,
      and the other used single photon emission computed tomography. There was a wide
      range of measurement techniques and timing of scans. Some studies found
      associations between delirium and cortical atrophy, and between ventricular
      enlargement and white matter lesion burden, but many studies did not control for
      potential confounders. Only two small studies of cerebral blood flow were
      identified, with both suggesting that there may be reduced regional cerebral
      blood flow, but the data were limited and somewhat inconsistent. CONCLUSIONS: The
      small sample sizes and other limitations of the studies identified in this review
      preclude drawing any clear conclusions regarding neuroimaging findings in
      delirium, but these studies suggest multiple avenues for future research.

PMID- 18707945
TI  - Unravelling the pathophysiology of delirium: a focus on the role of aberrant
      stress responses.
AB  - Delirium is a common and serious acute neuropsychiatric syndrome with core
      features of inattention and cognitive impairment, and associated features
      including changes in arousal, altered sleep-wake cycle, and other changes in
      mental status. The main risk factors are old age, cognitive impairment, and other
      comorbidities. Though delirium has consistent core clinical features, it has a
      very wide range of precipitating factors, including acute illness, surgery,
      trauma, and drugs. The molecular mechanisms by which these precipitating factors
      lead to delirium are largely obscure. In this article, we attempt to narrow down
      some specific causal pathways. We propose a basic classification for the
      etiological factors: (a) direct brain insults and (b) aberrant stress responses.
      Direct brain insults are largely indiscriminate and include general and regional
      energy deprivation (e.g., hypoxia, hypoglycaemia, stroke), metabolic
      abnormalities (e.g., hyponatraemia, hypercalcaemia), and the effects of drugs.
      Aberrant stress responses are conceptually and mechanistically distinct in that
      they constitute adverse effects of stress-response pathways, which, in health,
      are adaptive. Ageing and central nervous system disease, two major predisposing
      factors for delirium, are associated with alterations in the magnitude or
      duration of stress and sickness behavior responses and increased vulnerability to
      the effects of these responses. We discuss in detail two stress response systems
      that are likely to be involved in the pathophysiology of delirium: inflammation
      and the sickness behavior response, and activity of the limbic-hypothalamic
      pituitary-adrenal axis. We conclude by discussing the implications for future
      research and the development of new therapies for delirium.

PMID- 18707947
TI  - Predisposing and precipitating factors for delirium in a frail geriatric
      population.
AB  - OBJECTIVE: The aim of this study was to assess the possible predisposing
      aetiologic and short-term precipitating factors for delirium in acutely ill
      hospital patients with a heavy burden of comorbidities and medications. METHODS:
      Eighty-seven consecutive patients with acute delirium admitted to a general
      medicine unit were thoroughly examined, and the predisposing and precipitating
      factors of their delirium were assessed. RESULTS: In this population, an average
      of 5.2 predisposing factors and 3.0 potential precipitating factors for delirium
      was revealed, meaning an average of over eight possible aetiological causes for
      each patient. The most common precipitating factors were infections (n=72),
      metabolic abnormalities (n=52), adverse drug effects (n=41), and cardiovascular
      events (n=38). In addition, a number of very rare conditions were diagnosed after
      thorough assessments. CONCLUSION: Geriatric patients with acute delirium
      typically present with several concomitant predisposing factors for delirium
      exposing them to high vulnerability for the syndrome. In most patients, a number
      of possible etiological causes for delirium can be identified after a careful
      assessment, but their true pathogenetic pathway to the syndrome is unclear.

PMID- 18707948
TI  - Delirium detection in clinical practice and research: critique of current tools
      and suggestions for future development.
AB  - Delirium is underrecognized clinically. Many tools have been developed to assist
      with the diagnosis of delirium, and they vary greatly in purpose, quality, and
      administration time. It is suggested that future development of delirium
      assessment instruments be guided by a dichotomization of raters into expert and
      nonexpert groups. Careful consideration of the needs of the two groups suggests
      that assessment instruments designed for nonexperts should be entirely objective,
      whereas those instruments developed for experts should include the full range of
      constructs associated with the syndrome. This conceptualization is explored in
      detail, and existing assessment instruments are considered briefly in light of
      this position.

PMID- 18707949
TI  - Educating staff working in long-term care about delirium: the Trojan horse for
      improving quality of care?
AB  - OBJECTIVE: This study aimed to design a multicomponent intervention to improve
      delirium care in long-term care facilities for older people in the UK and to
      identify the levers and barriers to its implementation in practice. METHODS: The
      research incorporated the theoretical phase and Phase 1 of the Medical Research
      Council's framework. We designed a multicomponent intervention based on the
      evidence for effective interventions for delirium and for changing practice. We
      refined the intervention with input from care home staff and field visits to
      homes. Our intervention incorporated the following features: targeting risk
      factors for delirium, a 'delirium practitioner' functioning as a facilitator, an
      education package for care home staff, staff working groups at each home to
      identify barriers to improving delirium care and to produce tailored solutions, a
      local champion identified from the working groups, consultation, liaison with
      other professionals, and audit or feedback. The delirium practitioner recorded
      her experiences of delivering the intervention in a contemporaneous log. This was
      analysed using framework analysis to determine the levers and barriers to
      implementation. RESULTS: We introduced a multicomponent intervention for delirium
      in six care homes in Leeds. Levers to implementation included flexibility,
      tailoring training to staff needs, engendering pride and ownership amongst staff,
      and minimising extra work. Barriers included time constraints, poor organization,
      and communication problems. CONCLUSION: We were able to design and deliver an
      evidence-based multicomponent intervention for delirium that was acceptable to
      staff. The next steps are to establish its feasibility and effectiveness in
      modifying outcomes for residents of care homes.

PMID- 18707950
TI  - Systematic approaches to the prevention and management of patients with delirium.
AB  - Delirium is a common complication of acute illness in older people. Earlier and
      more reliable detection could be achieved by greater routine cognitive testing in
      older people. Research evidence suggests that episodes of delirium and duration
      of delirium could be reduced by about one third if systems of care that
      prioritized delirium risk factor amelioration were comprehensively adopted.
      Specialist delirium units have a place in leading and disseminating best
      practices. Health service regulators should consider monitoring delirium as an
      adverse health care outcome.

PMID- 18707951
TI  - Drug treatment of delirium: past, present and future.
AB  - OBJECTIVE: The aim of this review was to summarize and critically evaluate the
      current literature regarding the safety and efficacy of drug therapy in delirium.
      We also identified recent research developments and highlighted some ongoing
      clinical trials to explore future directions in drug treatment and prevention of
      delirium. METHODS: We conducted a literature search of Medline, Embase,
      PsychInfo, and Cochrane Review databases, which included both prospective and
      retrospective clinical trials and case studies on delirium and drug therapy in
      adult patients up to March 2008. Abstracts from recent topical conferences were
      also reviewed. Ongoing delirium drug studies were identified via the WHO
      International Clinical Trials Registry Platform Search Portal, accessed March 12,
      2008. RESULTS: The evidence base for effective drug treatment of delirium is
      restricted by limitations in many of the studies conducted to date. However,
      there has been an increase in the quantity and quality of delirium drug studies
      in recent years; preliminary reports and ongoing studies add to this trend.
      Although efficacy rates between typical and atypical antipsychotic agents are
      similar, the latter are associated with fewer extrapyramidal side effects.
      Prophylactic interventions with antipsychotic and cholinesterase inhibitors in
      high-risk patients provide an opportunity to improve postoperative patient care.
      Alternative techniques and medication opportunities could be explored in attempts
      to minimize drug induced delirium potential. CONCLUSIONS: Appropriate drug
      therapy should be considered part of systematic approaches to delirium treatment
      and prevention. There is a need for well-designed randomized, double-blind
      placebo-controlled trials investigating the drug management of various aspects of
      delirium, including delineating treatment by delirium subtype, dose ranging
      studies, and optimal duration of therapy.

PMID- 18707952
TI  - The ethics of consent in delirium studies.
AB  - BACKGROUND: Delirium is a syndrome of acute, fluctuating confusion, which affects
      older people who are unwell. Although common and associated with significant poor
      outcomes, little is known about its pathophysiology, prevention, or treatment.
      Delirium research could potentially deliver important benefits for patients and
      is urgently required. However, such research is challenging as it inevitably
      involves the recruitment of patients who have impaired capacity to consent, due
      to the nature of delirium itself and the fact that it is people with dementia or
      severe illness who are most at risk. AIM: This article explores the ethical
      tensions inherent in the need to protect vulnerable participants in delirium
      research and the urgent need for high-quality research in a neglected condition.
      CONCLUSIONS: The current research regulations are unnecessarily stringent and may
      impede good-quality delirium research. There is in particular the danger that
      they lead to the recruitment of unrepresentative study populations. We suggest a
      number of changes to the regulations, such as extending the use of the existing
      European Union procedures for registered medical practitioner proxy consent. We
      invite comments and feedback from the research community.

PMID- 18707953
TI  - Delirium issues in palliative care settings.
AB  - OBJECTIVE: The objective of this study is to provide an expert review of delirium
      in the context of palliative care. METHODS: Based on a primary selection
      criterion, firstly, studies were included for review if the population studied
      either had a diagnosis of advanced cancer or was receiving palliative care;
      alternatively, in the absence of data derived from these populations, studies
      conducted in other populations were included. Secondly, from the studies meeting
      the primary selection criterion, we selected those that examined specific
      standard outcome measures. Thirdly, we selected studies and literature reviews
      that identified delirium research issues. RESULTS: Delirium occurs commonly in
      the context of palliative care where it is likely to cause heightened distress
      for patients, carers, and families alike, and make interpretation of pain and
      other symptoms extremely difficult. There is a profound dearth of rigorous
      studies on delirium in this setting. Ambiguous terminology, varying definitions
      in internationally recognized classification systems, and failure to use
      validated assessment tools lead to wide-ranging incidence and prevalence of
      delirium episodes in such populations. Episodes are usually multifactorial in
      origin and may portend poor prognosis by preceding death in many cases. Despite
      this, many are often at least partially reversible with relatively low-burden
      interventions. The patient's disease status, previous quality of life, and prior
      expressed wishes regarding goals of care should all be taken into account.
      Antipsychotics are the pharmacotherapeutic agents most commonly used to control
      symptoms despite limited evidence either supporting their efficacy or examining
      their adverse event profile. Often, symptomatic control alone is indicated. In
      cases with refractory symptoms, deeper or "palliative" sedation may be required.
      CONCLUSION: Further research is needed regarding delirium recognition,
      phenomenology, the development of low-burden instruments for assessment, family
      education, predictive models for reversibility, and evidence-based guidelines on
      the appropriate use of palliative sedation.

PMID- 18707954
TI  - Designing clinical trials for the treatment of delirium.
AB  - There is a large body of empirical evidence for the usefulness of pharmacological
      treatment of delirium though there is a relative dearth of double-blind
      randomized clinical trials and few that are placebo controlled. There are no
      registration quality double-blind, randomized, placebo-controlled trials that
      evaluate efficacy and safety, nor is there a regulatory body in any country that
      has approved a drug with an indication to treat delirium. Reasons include
      inadequate training for design and implementation of clinical trials, too few
      patients at a given research site to adequately power a study, confounding
      variables such as dementia, multifactorial underlying etiologies that are
      difficult to control, inadequate understanding of the neuropathophysiology of
      delirium that could theoretically guide a choice of drugs, referral populations
      where the primary physician may not be the one interested in pursuing the
      research, confounding factors for attribution of safety signals, and lack of
      funding for an adequately powered trial outside of the pharmaceutical industry.
      This article provides basic information aimed at educating physicians and other
      clinicians about design and implementation considerations to conduct an
      adequately powered double-blind, randomized placebo-controlled clinical trial to
      evaluate a drug's efficacy in delirium.

PMID- 18707955
TI  - Preface. Interventional musculoskeletal radiology.

PMID- 18707956
TI  - Therapeutic and diagnostic joint injections.
AB  - Joint injections remain a valuable modality in the detection and treatment of
      intra-articular pathology. Over the past several decades, various diagnostic and
      therapeutic indications for joint injections have been developed. Imaging
      guidance for joint injection generally increases accuracy in joint aspirations
      and diagnostic blocks. Confirming intra-articular placement with steroid
      injections improves efficacy and reduces local complications. Administering intra
      articular contrast can improve the diagnostic performance of CT and MR imaging in
      many circumstances. This article focuses on the rationale for injections at
      different sites and describes different fluoroscopic approaches for common
      joints.

PMID- 18707957
TI  - Image-guided musculoskeletal biopsy.
AB  - Image guidance allows safe passage of needles, often into small and otherwise
      inaccessible lesions, and into the portions of the lesion most likely to yield
      useful samples, while avoiding damage to important structures. This article hopes
      to provide a useful guide to image-guided musculoskeletal biopsy for radiologists
      in practice and in training.

PMID- 18707958
TI  - Positron emission tomography-CT imaging in guiding musculoskeletal biopsy.
AB  - Positron emission tomography (PET)-computed tomography (CT) is a useful device in
      identifying musculoskeletal lesions that require biopsy. It can be used to
      localize the primary lesion, identify a site to biopsy, and evaluate metastatic
      lesions that require follow-up biopsies. Not all malignant tumors have
      hypermetabolic activity, and there are many benign lesions and physiologic
      processes that do have increased F-18 fluorodeoxyglucose uptake. Knowledge of
      these issues is important when reviewing PET-CT and directing subsequent
      musculoskeletal biopsies.

PMID- 18707959
TI  - Spinal injection procedures: a review of concepts, controversies, and
      complications.
AB  - The field of spinal injection procedures is growing at a tremendous rate. Many
      disciplines are involved, including radiology, anesthesiology, orthopedics,
      physiatry and rehabilitation medicine, as well as other specialties. However,
      there remains tremendous variability in the assessment of patients receiving
      these therapies, methods for evaluation of outcome, and in the understanding of
      where these procedures belong in the triaging of those who require surgery. In
      this article, we attempt to highlight the biologic concepts on which these
      therapies are based, controversies that have arisen with their increasing use,
      and a description of complications that have been reported.

PMID- 18707960
TI  - Musculoskeletal ultrasound intervention: principles and advances.
AB  - Ultrasound scan is an invaluable tool in the diagnosis and treatment of disorders
      of the musculoskeletal system. Core concepts that are common to most ultrasound
      guided procedures are reviewed, including an in-depth discussion regarding the
      use of injectable corticosteroids. Various aspects of intra-articular,
      intratendinous, bursal, and ganglion cyst intervention are discussed and
      promising advances in the treatment of chronic tendon disorders are presented.

PMID- 18707961
TI  - Embolization of musculoskeletal tumors.
AB  - Transarterial embolization should be considered in the treatment algorithm of
      primary or secondary bone tumors. Specific benefit is present where there is a
      high risk of bleeding at surgery, where there is spinal involvement and neural
      encroachment, where active bleeding is present, or in awkward surgical locations
      where prolonged surgery is anticipated.

PMID- 18707962
TI  - Venous malformations: classification, development, diagnosis, and interventional
      radiologic management.
AB  - Venous malformations are categorized as low-flow vascular malformations within
      the domain of vascular anomalies and are the most common vascular malformation
      encountered clinically. Venous malformations are by definition present at birth,
      undergo pari passu growth, and present clinically because of symptoms related to
      mass effect or stasis. Although diagnosis can usually be made by clinical history
      and examination, differentiation from other vascular and nonvascular entities
      often requires an imaging work-up that includes ultrasound, CT, MR imaging, and
      diagnostic phlebography. All decisions regarding imaging work-up and decision to
      treat must be coordinated though referral and discussions with a
      multidisciplinary team and be based on clearly defined clinical indications.
      Percutaneous image-guided sclerotherapy has become the mainstay of treatment for
      venous malformations and involves the introduction of any one of a number of
      endothelial-cidal sclerosants into the vascular spaces of the lesion, with each
      sclerosant possessing its own unique spectrum of advantages and disadvantages.

PMID- 18707963
TI  - Musculoskeletal interventional radiology: radiofrequency ablation.
AB  - Radiofrequency ablation is the use of low-voltage high-frequency electrical
      energy to heat and destroy abnormal tissues within the human body. It has gained
      increasing acceptance as both a primary and secondary form of treatment in the
      musculoskeletal system because of its excellent safety profile, ease of use, and
      technical success. In the musculoskeletal system, radiofrequency ablation may be
      used to treat a wide range of lesions that include primary lesions such as
      osteoid osteomas and a variety of metastases both within the osseous skeleton as
      well as those lying within the muscles and soft tissues. In this chapter, a
      background to the principles, physics, and indications of radiofrequency is
      presented as well as an in-depth description of radiofrequency ablation
      techniques that may be utilized in the musculoskeletal system.

PMID- 18707964
TI  - Percutaneous vertebral augmentation: vertebroplasty, kyphoplasty and
      skyphoplasty.
AB  - Percutaneous vertebroplasty is a safe, inexpensive, and effective interventional
      vertebral augmentation technique that provides pain relief and stabilization in
      carefully selected patients with severe back pain due to vertebral compression.
      Complications from percutaneous vertebroplasty can be devastating, but are rare
      and avoidable with application of a meticulous technique. Percutaneous
      vertebroplasty has a role in the management pathway of patients presenting with
      painful vertebral compression fractures. Kyphoplasty uses a balloon tamp with the
      aim of restoring vertebral body height, improving kyphotic deformity, and
      creating a cavity into which bone cement is injected. Kyphoplasty is as effective
      and safe as vertebroplasty in treatment of painful vertebral compression
      fractures. Skyphoplasty, a modification of kyphoplasty, is a promising new
      technique.

PMID- 18707965
TI  - The changing face of heart disease prevention.

PMID- 18707966
TI  - Child survival: India and China's challenges.

PMID- 18707967
TI  - The hub of innovation: Academic Health Science Centres.

PMID- 18707968
TI  - Mechanical reperfusion: treat well, treat on time too.

PMID- 18707969
TI  - Renin-angiotensin blockade and kidney disease.

PMID- 18707971
TI  - Developments for funding clinical research in the UK.

PMID- 18707970
TI  - Lipid lowering: what and when to monitor.

PMID- 18707972
TI  - Merging evidence-based and mechanism-based medicine.

PMID- 18707975
TI  - Intensive antiplatelet therapy for reduction of ischaemic events.

PMID- 18707976
TI  - Intensive antiplatelet therapy for reduction of ischaemic events.

PMID- 18707977
TI  - Guidelines for anticoagulant use in acute coronary syndromes.

PMID- 18707981
TI  - Carotid bruits and cardiovascular death or myocardial infarction.

PMID- 18707982
TI  - In search of lost time: age, CVD, and intensive statin treatment.

PMID- 18707983
TI  - Adverse events in clinical trials: is a new approach needed?

PMID- 18707984
TI  - William Harvey Trophy: honouring the discoverer of circulation with a round of
      golf.

PMID- 18707985
TI  - Prehospital initiation of tirofiban in patients with ST-elevation myocardial
      infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double
      blind, randomised controlled trial.
AB  - BACKGROUND: The most effective magnitude and timing of antiplatelet therapy is
      important in patients with acute ST-elevation myocardial infarction (STEMI). We
      investigated whether the results of primary coronary angioplasty (PCI) can be
      improved by the early administration of the glycoprotein IIb/IIIa blocker
      tirofiban at first medical contact in the ambulance or referral centre. METHODS:
      We undertook a double-blind, randomised, placebo-controlled trial in 24 centres
      in the Netherlands, Germany, and Belgium. Between June 29, 2006, and Nov 13,
      2007, 984 patients with STEMI who were candidates to undergo PCI were randomly
      assigned to either high-bolus dose tirofiban (n=491) or placebo (N=493) in
      addition to aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg).
      Randomisation was by blinded sealed kits with study drug, in blocks of four. The
      primary endpoint was the extent of residual ST-segment deviation 1 h after PCI.
      Analysis was by intention to treat. The trial is registered, number
      ISRCTN06195297. FINDINGS: 936 (95%) patients were randomly assigned to treatment
      after a prehospital diagnosis of myocardial infarction in the ambulance. Median
      time from onset of symptoms to diagnosis was 76 min (IQR 35-150). Mean residual
      ST deviation before PCI (10.9 mm [SD 9.2] vs 12.1 mm [9.4], p=0.028) and 1 h
      after PCI (3.6 mm [4.6] vs 4.8 mm [6.3], p=0.003) was significantly lower in
      patients pretreated with high-bolus dose tirofiban than in those assigned to
      placebo. The rate of major bleeding did not differ significantly between the two
      groups (19 [4%] vs 14 [3%]; p=0.36). INTERPRETATION: Our finding that routine
      prehospital initiation of high-bolus dose tirofiban improved ST-segment
      resolution and clinical outcome after PCI, emphasises that further platelet
      aggregation inhibition besides high-dose clopidogrel is mandated in patients with
      STEMI undergoing PCI.

PMID- 18707986
TI  - Renal outcomes with telmisartan, ramipril, or both, in people at high vascular
      risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled
      trial.
AB  - BACKGROUND: Angiotensin receptor blockers (ARB) and angiotensin converting enzyme
      (ACE) inhibitors are known to reduce proteinuria. Their combination might be more
      effective than either treatment alone, but long-term data for comparative changes
      in renal function are not available. We investigated the renal effects of
      ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in
      patients aged 55 years or older with established atherosclerotic vascular disease
      or with diabetes with end-organ damage. METHODS: The trial ran from 2001 to 2007.
      After a 3-week run-in period, 25 620 participants were randomly assigned to
      ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a
      combination of both drugs (n=8502; median follow-up was 56 months), and renal
      function and proteinuria were measured. The primary renal outcome was a composite
      of dialysis, doubling of serum creatinine, and death. Analysis was by intention
      to treat. This study is registered with ClinicalTrials.gov, number NCT00153101.
      FINDINGS: 784 patients permanently discontinued randomised therapy during the
      trial because of hypotensive symptoms (406 on combination therapy, 149 on
      ramipril, and 229 on telmisartan). The number of events for the composite primary
      outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%];
      hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination
      therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome,
      dialysis or doubling of serum creatinine, was similar with telmisartan (189
      [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with
      combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated
      glomerular filtration rate (eGFR) declined least with ramipril compared with
      telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or
      combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin
      excretion was less with telmisartan (p=0.004) or with combination therapy
      (p=0.001) than with ramipril. INTERPRETATION: In people at high vascular risk,
      telmisartan's effects on major renal outcomes are similar to ramipril. Although
      combination therapy reduces proteinuria to a greater extent than monotherapy,
      overall it worsens major renal outcomes.

PMID- 18707987
TI  - Acute myocardial infarction.
AB  - Modern management of acute myocardial infarction is built on a clinical evidence
      base drawn from many studies undertaken over the past three decades. The
      evolution in clinical practice has substantially reduced mortality and morbidity
      associated with the condition. Key to this success is the effective integration
      of antithrombotic therapy combined with timely reperfusion, either primary
      percutaneous coronary intervention or fibrinolysis for ST-elevation myocardial
      infarction, and invasive investigation and revascularisation for non-ST-elevation
      myocardial infarction, underpinned by risk stratification and optimised systems
      of care. After the development of troponin assays for the detection of
      myonecrosis, the universal definition and classification of myocardial infarction
      now indicates the underlying pathophysiology. Additionally, an increasing
      appreciation of the importance of adverse events, such as bleeding, has emerged.
      Remaining challenges include the effective translation of this evidence to all
      patients with myocardial infarction, especially to those not well represented in
      clinical trials who remain at increased risk of adverse events, such as elderly
      patients and those with renal failure. On a global level, the epidemic of
      diabetes and obesity in the developed world and the transition from infectious
      diseases to cardiovascular disease in the developing world will place an
      increasing demand on health-care infrastructures required to deliver time
      dependent and resource-intensive care. This Seminar discusses the underlying
      pathophysiology, evolving perspectives on diagnosis, risk stratification, and the
      invasive and pharmacological management of myocardial infarction.

PMID- 18707988
TI  - Growing pains--and a heart attack.

PMID- 18707989
TI  - Supraventricular tachycardia. Foreword.

PMID- 18707990
TI  - Supraventricular tachycardia--part I.
AB  - Supraventricular tachycardias (SVTs) affect all age groups and are a source of
      significant morbidity. They are frequently encountered in otherwise healthy
      individuals without structural heart disease. Advances in the understanding of
      their mechanisms and anatomical locations have led to highly effective
      pharmacologic and nonpharmacologic treatment strategies. Recognition,
      identification, and differentiation of the various SVTs are of great importance
      in formulating an effective treatment strategy. Developments over the past four
      decades have made possible the accurate diagnosis of SVTs. Today, advances in
      catheter design, energy delivery systems, mapping systems, and remote navigation
      systems have rendered the ablation of most SVTs safe and effective. This
      monograph provides an in-depth discussion of the history, presentation,
      mechanism, and treatment strategies of the most commonly encountered SVTs. The
      monograph is divided into two parts. The first part is presented here.

PMID- 18707991
TI  - The balloon dilating catheter as an instrument in sinus surgery.
AB  - The use of the balloon dilating catheter has been a divisive topic in the
      rhinology community. This commentary addresses shortcomings that are commonly
      remarked upon by opponents of this technology and reviews the clinical history of
      the device as detailed in the literature. The reported orbital and cranial
      complications are described, and the major complication rate per sinus is
      calculated at 0.0035%. Most importantly, the balloon dilating catheter is
      stressed as being a unique instrument that can be used to enlarge a sinus ostium
      and dilate a sinus outflow tract in the most mucosal-sparing method possible,
      regardless of whether it is used in conjunction with standard instrumentation or
      as a stand-alone device.

PMID- 18707992
TI  - Balloon catheter sinusotomy: one-year follow-up--outcomes and role in functional
      endoscopic sinus surgery.
AB  - OBJECTIVE: The primary objective was to assess the long-term effectiveness of
      balloon catheter sinusotomy. METHODS: Patients who had sinus ostia dilated with
      balloon catheters were prospectively evaluated 1 year after surgery with nasal
      endoscopy, a CT scan, and the Sino-Nasal Outcome Test (SNOT-20). RESULTS: Sixty
      six patients (202 sinuses) were examined. One hundred seventy-two of 202 sinus
      ostia (85%) were endoscopically patent, 1 percent (2/202) were nonpatent, and
      ostial patency could not be determined by endoscopy in 28 of 202 (14%). In these
      "indeterminate" sinuses, the CT scans were normal in 13, implying functional
      patency in 91.6 percent of sinuses (185/202). Sinus CT scan scores were 1.95 at 1
      year versus 8.89 at baseline (P < 0.001), and 1-year SNOT-20 scores (0.91) were
      significantly improved from baseline (2.14, P < 0.0001). CONCLUSION: Balloon
      catheter sinusotomy results were durable over the study period, showing long-term
      effectiveness.

PMID- 18707993
TI  - Long-term outcome analysis of balloon catheter sinusotomy: two-year follow-up.
AB  - OBJECTIVE: Assess two-year postoperative clinical outcomes for patients receiving
      balloon catheter sinusotomy. METHODS: Patients who had sinus ostia dilated with
      balloon catheters were prospectively evaluated two years after surgery by
      Sinonasal Outcome Test (SNOT-20) and computed tomographic (CT) scan. RESULTS:
      Sixty-five patients (195 ballooned sinuses) were followed for two years after
      surgery, including 34 "balloon-only" patients and 31 "hybrid" patients. SNOT-20
      symptom scores were significantly improved from baseline (0.87 vs 2.17 baseline,
      P < 0.001) and stable compared to six months and one year; this was the case for
      both balloon-only (1.09 vs 2.09, P < 0.001) and hybrid (0.64 vs 2.26, P < 0.001)
      patients. Lund-MacKay CT scores were significantly improved from baseline (2.69
      vs 9.66, P < 0.001) and stable compared to one year, confirmed for both balloon
      only (1.75 vs 5.67, P < 0.015) and hybrid (3.25 vs 12.05, P < 0.001) subsets of
      patients. A total of 85% of patients reported improvement of their sinus
      symptoms, with 15% same and 0% worsened. Revision treatment was required in seven
      of 195 sinuses (3.6%) in six of 65 patients (9.2%). CONCLUSION: Patients who
      receive balloon catheter sinusotomy in endoscopic sinus surgery have significant
      improvement in symptoms two years after surgery. Radiographic evidence also
      confirms resolution of disease after two years. This demonstrates durability of
      clinical results previously reported at 24 weeks and one year after surgery.

PMID- 18707994
TI  - Magnet status application.

PMID- 18707995
TI  - Measuring venous insufficiency objectively in the clinical setting.
AB  - The purpose of this article is to propose a screening procedure to assess venous
      insufficiency with a hand-held photoplethysmography (PPG) instrument in the
      clinical setting. PPG is noninvasive technology that is used as part of venous
      assessment of the lower extremities. Although duplex ultrasound remains the
      industry gold standard for assessment, there are many situations in which access
      or expertise is not available. The measurement of venous refill time with PPG,
      one measure of venous insufficiency, is becoming increasingly more prevalent in
      research settings; however, PPG is underused in clinical settings. Rapid venous
      refill time </= 20 seconds is associated with chronic venous disorders, and its
      measurement in clinical settings as a screening mechanism may provide useful data
      to augment diagnostic and therapeutic decision making. Future research is needed
      to establish a best-practice guideline for venous assessment in clinical settings
      to validate using PPG.

PMID- 18707996
TI  - Testing the effectiveness of the Amputee Mobility Protocol: a pilot study.
AB  - We studied prolonged length of stay (LOS) in the acute care setting on a medical
      surgical vascular unit, related to loss of functional mobility status after lower
      extremity amputation, and implementation of the Amputee Mobility Protocol (AMP)
      as a standard of care for all patients pre- and post-lower extremity amputation
      who were admitted to the medical-surgical vascular unit. A comparative pre-post
      observational study evaluated the effect of AMP on level of functional mobility
      and LOS after lower extremity amputation in the patient population on the medical
      surgical vascular unit. Data was collected retrospectively from patient chart
      reviews from November of 2004 to March of 2005 for the pre-AMP group and through
      concurrent patient chart reviews from November of 2005 to March of 2006 for the
      post-AMP group. Dependent variables included functional mobility and LOS, which
      were evaluated by a modified Functional Independence Measure (FIM) score and the
      hospital LOS. Forty-four eligible patients were enrolled in the AMP pilot study
      during a 5-month period. The sample population consisted of 30 patients pre-AMP
      and 14 patients post-AMP. LOS for transmetatarsal amputations decreased by 0.7
      days, whereas functional mobility increased by a minimum of one level in the
      modified FIM score. Functional mobility increased for transtibial amputations by
      one level and transfemoral amputations by 2 levels using the modified FIM score.
      LOS increased for patients undergoing transtibial (7.1 days) and transfemoral
      (2.7 days) amputations. This quality improvement project heightened staff
      awareness regarding ambulation and its impact on functional mobility and early
      discharge. Vascular nurses were able to affect patients' functional mobility and
      LOS by implementing a standardized AMP. Data showed that using the standardized
      AMP increased patients' functional mobility but did not significantly decrease
      acute care setting LOS. The AMP continues to be used for this patient population
      because of its impact on functional mobility and independence. This pilot study
      relates to 3 of the top 20 vascular research priorities: 1) an interdisciplinary
      strategy to improve the patient's level of functional independence and thereby
      decrease LOS and cost; 2) the nursing intervention of early, predetermined
      ambulation schedules will increase the nursing knowledge of strategies that
      facilitate recovery after vascular surgery in this population; and 3) factors
      that affect patient outcomes after these three major vascular procedures will be
      addressed in pilot outcomes. Limitations of the AMP pilot study included the
      small sample size, staff turnover, and lack of a concurrent control group. The
      next phase of this project will create and implement a similar activity protocol
      for patients after abdominal aortic aneurysm repair and various types of lower
      extremity bypass procedures.

PMID- 18707997
TI  - Endovascular treatment of atherosclerosis at the aortoiliac bifurcation with
      kissing stents or distal aortic stents: a temporary solution or durable
      improvement?
AB  - To evaluate medium-term technical and clinical success after endovascular
      treatment of stenosis or occlusion at the aortoiliac bifurcation with a distal
      aortic stent or kissing stents. Between 1995 and 2004, 25 patients were included
      in the study. Nine patients were treated with an aortic stent, and 16 patients
      were treated with kissing stents. Clinical and radiologic findings were
      retrospectively reviewed, and statistical analysis was performed. In all cases,
      the procedure was technically successful. Hemodynamic success was observed in 22
      patients (88%), and clinical success was observed in 23 patients (92%). After a
      median follow-up of 21 months, 8 patients developed a restenosis (n = 6) or
      occlusion (n = 2). Two patients with restenosis were treated successfully with
      aortic bifurcation grafts, and 4 patients underwent endovascular reintervention.
      No risk factors for restenosis were identified. Primary patency was 87% after 1
      year and 65% after 2 years. Secondary patency was 90% after 1 year and 72% after
      2 years. At the last outpatient control, 22 patients (88%) were free of symptoms.
      Endovascular treatment of symptomatic aortoiliac atherosclerosis at the
      aortoiliac bifurcation by means of a distal aortic stent or kissing stents can be
      used successfully with durable improvement in the majority of patients. We
      recommend it as the initial treatment modality.

PMID- 18707999
TI  - Advances in clinical genetics. Part IV. Introduction.

PMID- 18708000
TI  - A review of newborn screening in the era of tandem mass spectrometry: what's new
      for the pediatric neurologist?
AB  - Newborn screening has evolved from a single test for a single metabolite to a
      test that detects more than 90 metabolites on a single blood spot. In the past
      decade, the panel of newborn-screening disorders has rapidly expanded and will
      continue to grow as more is discovered about the human genome. It continues to be
      a very sensitive population screening tool that is susceptible to the status of
      the infant and the timing of the specimen collection. This review discusses the
      disorders that should be detected on neonatal bloodspot screening and what
      pediatric neurologists may see in those that were detected on newborn screening
      and treated and those that have been untreated.

PMID- 18708001
TI  - The child neurologist's role in newborn screening programs: a commentary.

PMID- 18708002
TI  - Current strategies in the management of lysosomal storage diseases.
AB  - Lysosomal storage diseases (LSDs) comprise a diverse group of over 40 clinically
      distinct inherited disorders. LSDs are progressive and may present at any age
      affecting any number of tissues and organ systems. They result from a genetic
      defect in cellular transport or metabolism of molecules within the lysosome.
      Treatment is directed toward symptomatic care of secondary complications for most
      of these diseases. For some individuals, hematopoietic stem cell transplantation
      or enzyme-replacement therapy can be effective. However, limitations in these
      therapies still exist. To date, there is no cure for any of the LSDs. Early
      diagnosis and treatment is essential for optimal treatment; this lends support to
      implementing mass newborn screening for LSDs.

PMID- 18708003
TI  - Inherited metabolic diseases in neurodevelopmental and neurobehavioral disorders.
AB  - In the past few years, there has been a veritable explosion in the discovery of
      "new" inborn errors of metabolism. These new conditions are involved in complex
      pathways of intermediary metabolism affecting processes heretofore unknown. The
      phenotypes of these new conditions are in many ways milder than the classically
      described metabolic disorders. Several of these conditions present as
      nonsyndromic neurodevelopmental and/or neurobehavioral disorders. As such, these
      conditions should be considered in the differential diagnosis of conditions such
      as mental retardation, autism spectrum disorders, movement disorders, and
      cerebral palsy. This article reviews several of these recently described
      conditions including the clinical presentation, the biochemical profile, the
      diagnostic approach, and therapeutic options.

PMID- 18708004
TI  - Neurologic damage and neurocognitive dysfunction in urea cycle disorders.
AB  - Although the survival of patients who have urea cycle disorders has improved with
      the use of modalities such as alternative pathway therapy and hemodialysis,
      neurologic outcome is suboptimal. Patients often manifest with a variety of
      neurologic abnormalities, including cerebral edema, seizures, cognitive
      impairment, and psychiatric illness. Current hypotheses of the pathogenesis
      underlying brain dysfunction in these patients have focused on several lines of
      investigation, including the role of glutamine in causing cerebral edema,
      mitochondrial dysfunction leading to energy failure and the production of free
      radicals, and altered neurotransmitter metabolism. Advances in understanding the
      pathogenetic mechanisms underlying brain impairment in urea cycle disorders may
      lead to the development of therapies designed to interfere with the molecular
      cascade that ultimately leads to cerebral edema and other brain pathological
      findings.

PMID- 18708005
TI  - Mitochondrial fatty-acid oxidation disorders.
AB  - Inherited defects in mitochondrial fatty-acid beta-oxidation comprise a group of
      at least 12 diseases characterized by distinct enzyme or transporter
      deficiencies. Most of these diseases have a variable age of onset and clinical
      severity. Symptoms are often episodic and associated with mild viral illness,
      physiologic stress, or prolonged exercise that overwhelms the ability of
      mitochondria to oxidize fatty acids. Depending on the specific genetic defect,
      patients develop fasting hypoketotic hypoglycemia, cardiomyopathy,
      rhabdomyolysis, liver dysfunction, or sudden death. Neuropathy and pigmentary
      retinopathy are seen in some of the diseases. The diagnosis is based on finding
      an accumulation of specific biochemical markers such as acylcarnitine metabolites
      in blood and urinary dicarboxylic acids and acylglycines. Confirmatory testing
      requires enzymatic studies and DNA analysis. Therapeutic approaches are generally
      effective in preventing severe symptomatic episodes, including sudden death.
      Newborn screening for fatty-acid oxidation disorders promises to identify many
      affected patients before the onset of symptoms.

PMID- 18708006
TI  - Topical antibiotic/steroid medication for infection prophylaxis after strabismus
      surgery: is it custom or science?

PMID- 18708007
TI  - Investigating mechanisms of strabismus in nonhuman primates.

PMID- 18708008
TI  - The effect of colored crowding bars on the HOTV visual acuity test in amblyopic
      patients.
AB  - BACKGROUND: Colored versus black crowding bars surrounding a black optotype may
      induce a greater level of interest in visual acuity testing in young children. To
      evaluate the adequacy of colored bars for a satisfactory crowding effect in
      children with amblyopia, we compared visual acuity measurements using black
      versus red, green, or yellow bars. METHODS: To choose the best color to compare
      with black, 53 patients with amblyopia were randomly assigned to 1 of 3 crowding
      bar colors. Subjects had the visual acuity of each eye measured with black HOTV
      optotypes and bars and then with black optotypes and either red, green, or yellow
      bars. In a second phase of the study red crowding bars were compared with black
      in a group of 48 different patients with amblyopia. RESULTS: The difference in
      logMAR visual acuity between amblyopic eyes tested with red versus black crowding
      bars was not statistically significant (mean visual acuities of -0.24 and -0.26,
      respectively; p = 0.315), but the difference was significant with either green (
      0.30 and -0.34; p = 0.047) or yellow (-0.14 and -0.24; p = 0.0003). In the
      nonamblyopic eyes none of the colored crowding bars yielded significantly
      different visual acuity measurements compared with black. In the second phase of
      the study red crowding bars yielded an average of one letter worse visual acuity
      than black bars, but the difference was not statistically significant.
      CONCLUSIONS: Red crowding bars surrounding black optotypes are an acceptable
      alternative to black crowding bars for the measurement of visual acuity in
      amblyopic eyes.

PMID- 18708009
TI  - Hang-back recession of inferior oblique muscle in V-pattern strabismus with
      inferior oblique overaction.
AB  - INTRODUCTION: Although hang-back recession has widely been used as a weakening
      procedure on extraocular muscles, its effectiveness has mostly been studied for
      rectus muscles. We report a surgical technique for recessing the inferior oblique
      muscle and evaluate its effectiveness in V-pattern strabismus with inferior
      oblique overaction (IOOA). METHODS: Fifteen patients with V-pattern strabismus
      and IOOA, 7 with V exotropia, and 8 with V esotropia underwent hang-back
      recession of inferior oblique muscle in addition to horizontal muscle surgery
      when required. The surgical technique consisted of free suspension of one or both
      inferior oblique muscles 10 mm along their physiological path using 6-0
      polyglactin 910 sutures bridging the cut ends of muscle. RESULTS: The mean
      preoperative V pattern in the V-exotropia group was 22(Delta) +/- 6(Delta) and
      25(Delta) +/- 7(Delta) in V-esotropia group. The mean correction of V pattern
      after a mean follow-up period of 8 +/- 1 months was 19(Delta) +/- 2(Delta) for
      the V-exotropia group and 22(Delta) +/- 7(Delta) months for the V-esotropia
      group. Mean correction of IOOA in the V-exotropia group was 18(Delta) +/-
      5(Delta); in the V-esotropia group, mean correction was 20(Delta) +/- 6(Delta) in
      the right eye and 18(Delta) +/- 2(Delta) in the left eye. CONCLUSIONS: Hang-back
      recession of inferior oblique is another surgical procedure for correction of
      both V pattern and IOOA in V-pattern strabismus.

PMID- 18708010
TI  - A conjunctival cyst with delayed internal hemorrhage after strabismus surgery.

PMID- 18708011
TI  - Congenital cranial dysinnervation disorders/syndrome.

PMID- 18708012
TI  - Optical coherence tomography as an adjunctive tool for diagnosing pediatric
      pseudotumor cerebri.

PMID- 18708015
TI  - Myectomy versus anterior transposition for inferior oblique overaction.

PMID- 18708017
TI  - Distance stereoacuity in prism-induced convergence stress.

PMID- 18708018
TI  - Effect of axial length and keratometry measurement error on intraocular lens
      implant power prediction formulas in pediatric patients.

PMID- 18708020
TI  - Rituximab (MabThera) therapy and safety management. Clinical tool guide.

PMID- 18708022
TI  - Inflammatory bowel disease following solid organ transplantation.
AB  - Inflammatory bowel disease (IBD) is a T cell driven inflammatory condition of the
      gut. Following solid organ transplantation (SOT), de novo IBD has been reported
      despite anti-T cell therapy for the prevention of organ rejection. This paradox
      is illustrated with a case report, highlighting the difficult diagnostic
      criteria, the potential role of Damage or Pathogen Associated Molecular Pattern
      Molecules [DAMPs and PAMPs] that drives aspects of ongoing inflammation within
      the transplanted organ as well as the intestine, and the therapeutic strategies
      applied. Recurrent IBD is more common than de novo IBD following transplantation,
      with cumulative risks ten years after orthotopic liver transplantation of 70% and
      30%, respectively. Furthermore, the annual incidence of de novo IBD following
      solid organ transplantation has been estimated to be 206 cases/100,000 or ten
      times the expected incidence of IBD in the general population (approximately 20
      cases/100,000). The association of IBD with other autoimmune conditions such as
      primary sclerosing cholangitis and autoimmune hepatitis, both common indications
      for liver transplantation, may play a contributory role, particularly in view of
      the observation that IBD is more common following liver transplant than other
      solid organ transplants. Recurrent IBD following transplant appears to run a more
      aggressive course than de novo IBD, with a higher proportion requiring colectomy
      for medically refractory disease. Risk factors that have been associated with
      development of post-transplant IBD include acute CMV infection and the use of
      tacrolimus.

PMID- 18708023
TI  - Identification of a Btk mutation in a dysgammaglobulinemic patient with reduced B
      cells: XLA diagnosis or not?
AB  - The identification of a Btk mutation in a male patient with <2% CD19(+) B cells
      warrants making the diagnosis of X-linked Agammaglobulinemia (XLA). Herein we
      report the case of a 31 year-old male with a gradual decline of peripheral B
      lymphocytes and low IgA and IgM but normal IgG levels. His clinical history
      revealed recurrent respiratory and skin infections, sclerosing cholangitis and
      chronic obstructive pancreatitis. Molecular studies revealed a novel aminoacidic
      substitution in Btk protein (T316A). His mother, maternal aunts and a maternal
      female cousin were heterozygotes for the same Btk mutation and were variably
      affected with pulmonary emphysema. This is a puzzling case where the patient's
      clinical history and laboratory findings divorce molecular genetics. Either this
      case confirms the variable expressivity of XLA disease or the T316A change in Btk
      SH2 domain is a novel non-pathogenic mutation and another unknown gene alteration
      is responsible for the disease.

PMID- 18708024
TI  - A sensitive and reproducible fluorescent-based HPLC assay to measure the activity
      of acid as well as neutral beta-glucocerebrosidases.
AB  - The activity of lysosomal acid beta-glucocerebrosidase (AGC, EC 3.2.1.45), which
      hydrolyzes the O-glycosidic linkage between D-glucose and ceramide of
      glucosylceramide (GlcCer), is a marker for the diagnosis of Gaucher disease
      because the disease is caused by dysfunction of AGC due to mutations in the gene.
      The activity of AGC is potently inhibited by conduritol B epoxide (CBE), whereas
      CBE-insensitive nonlysosomal neutral beta-glucocerebrosidase (NGC) activities
      have been found in various vertebrates, including humans. We report here a new
      reliable method to determine AGC as well as NGC activities using normal-phase
      high-performance liquid chromatography (HPLC) and NBD (4-nitrobenzo-2-oxa-1,3
      diazole)- or BODIPY (4,4-difluoro-4-boro-3a,4a-diaza-s-indacene)-labeled GlcCer
      as a substrate. The reaction products of the enzymes, C6-NBD-ceramide and C12
      BODIPY-ceramide, were clearly separated from the corresponding substrates on a
      normal-phase column within 5 min using a different solvent system. Reaction
      products could be detected quantitatively at concentrations ranging from 50 fmol
      to 50 pmol for C6-NBD-ceramide and from 10 fmol to 5 pmol for C12-BODIPY
      ceramide. V(max)/K(m) values of human fibroblast AGC for fluorescent GlcCer were
      much higher than those for 4-methylumbelliferyl-beta-d-glucoside (4MU-Glc), which
      is used prevalently for Gaucher disease diagnosis. As a result, AGC activity was
      detected quantitatively using fluorescent GlcCer, but not 4MU-Glc, using 5 microl
      of human serum or 1 x 10(4) cultured human fibroblasts. The current method
      clearly showed the decrease of AGC activities in fibroblasts and serum from the
      patient with Gaucher disease compared with normal individuals, suggesting that
      the method is applicable for the diagnosis of Gaucher disease. Furthermore, this
      method was found to be useful for measuring the activities of nonlysosomal NGC of
      various cells and tissues in the presence of CBE.

PMID- 18708025
TI  - GLP-1 and related peptides cause concentration-dependent relaxation of rat aorta
      through a pathway involving KATP and cAMP.
AB  - Increasing evidence from both clinical and experimental studies indicates that
      the insulin-releasing hormone, glucagon-like peptide-1 (GLP-1) may exert
      additional protective/reparative effects on the cardiovascular system. The aim of
      this study was to examine vasorelaxant effects of GLP-1(7-36)amide, three
      structurally-related peptides and a non-peptide GLP-1 agonist in rat aorta.
      Interestingly, all GLP-1 compounds, including the established GLP-1 receptor
      antagonist, exendin (9-39) caused concentration-dependent relaxation. Mechanistic
      studies employing hyperpolarising concentrations of potassium or glybenclamide
      revealed that these relaxant effects are mediated via specific activation of ATP
      sensitive potassium channels. Further experiments using a specific membrane
      permeable cyclic AMP (cAMP) antagonist, and demonstration of increased cAMP
      production in response to GLP-1 illustrated the critical importance of this
      pathway. These data significantly extend previous observations suggesting that
      GLP-1 may modulate vascular function, and indicate that this effect may be
      mediated by the GLP-1 receptor. However, further studies are required in order to
      establish whether GLP-1 related agents may confer additional cardiovascular
      benefits to diabetic patients.

PMID- 18708026
TI  - Brefeldin A inhibits cholesterol efflux without affecting the rate of cellular
      uptake and re-secretion of apolipoprotein A-I in adipocytes.
AB  - A possible role of cellular uptake and re-secretion of apoA-I in the mechanism of
      cholesterol efflux induced by apoA-I was investigated using a novel experimental
      approach. Incubation of adipocytes with a recombinant human apoA-I containing a
      consensus PKA phosphorylation site, pka-ApoA-I, leads to the appearance of
      phosphorylated protein in the cell culture medium unambiguously proving cellular
      uptake and re-secretion of pka-ApoA-I. Phosphorylation of apoA-I is abolished by
      PKA inhibitors and enhanced by PKA activators demonstrating the specific
      involvement of PKA. Studies on the concentration dependence of pka-apoA-I
      phosphorylation and competition experiments with human apoA-I suggest that
      apolipoprotein uptake is a receptor mediated process. A possible role of apoA-I
      recycling in the mechanism of cholesterol efflux was investigated by determining
      the rates of apoA-I induced cholesterol efflux and apoA-I recycling in the
      presence and in the absence of Brefeldin A (BFA). The studies showed that BFA
      strongly inhibits cholesterol efflux without affecting the rate of apoA-I
      recycling. Since BFA affects vesicular trafficking of ABCA1, this study suggests
      that the interaction of apoA-I with ABCA1 does not mediate apolipoprotein uptake
      and re-secretion. This result suggests that lipidation of apoA-I and
      apolipoprotein uptake/re-secretion are independent processes.

PMID- 18708027
TI  - Membrane tension regulates water transport in yeast.
AB  - Evidence that membrane surface tension regulates water fluxes in intact cells of
      a Saccharomyces cerevisiae strain overexpressing aquaporin AQY1 was obtained by
      assessing the osmotic water transport parameters in cells equilibrated in
      different osmolarities. The osmotic water permeability coefficients (P(f))
      obtained for yeast cells overexpressing AQY1 incubated in low osmolarity buffers
      were similar to those obtained for a double mutant aqy1aqy2 and approximately
      three times lower (with higher activation energy, E(a)) than values obtained for
      cells incubated in higher osmolarities (with lower E(a)). Moreover, the initial
      inner volumes attained a maximum value for cells equilibrated in lower
      osmolarities (below 0.75 M) suggesting a pre-swollen state with the membrane
      under tension, independent of aquaporin expression. In this situation, the
      impairment of water channel activity suggested by lower P(f) and higher E(a)
      could probably be the first available volume regulatory tool that, in cooperation
      with other osmosensitive solute transporters, aims to maintain cell volume. The
      results presented point to the regulation of yeast water channels by membrane
      tension, as previously described in other cell systems.

PMID- 18708028
TI  - A stress-dependent SUMO4 sumoylation of its substrate proteins.
AB  - Here we performed studies to demonstrate SUMO4 maturation process. Unlike other
      SUMO proteins, cells under physiological condition mediate a rapid degradation
      for SUMO4. However, when cells under stressed condition, SUMO4 can be matured by
      the stress-induced endogenous hydrolase and be able to covalently conjugate to
      its substrate proteins. Furthermore, we failed to obtain evidence supporting a
      role for proline-90 unique to SUMO4 in its activation and functionality. Both
      wild-type SUMO4 and SUMO4-P90Q can be hydrolyzed by the stressed RAW264.7 cell
      lysates, and no significant functional difference between SUMO4, SUMO4-P90Q, and
      SUMO4-GG (matured form) was observed as determined by luciferase assay. However,
      the C-terminal di-glycine motif, a prerequisite for sumoylation, is necessary for
      SUMO4 to exert its functional activity. These data not only confirmed our
      previous published data, but also provided additional evidence suggesting a role
      for SUMO4 sumoylation in the regulation of intracellular stress.

PMID- 18708029
TI  - Antioxidant effects of equol on bovine aortic endothelial cells.
AB  - This study is to examine the effects of equol on the H(2)O(2)-induced death of
      bovine aortic endothelial cells (bAECs) and the mechanism of its protective
      effects. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] assay
      showed that in the control group, cell survival rate decreased significantly,
      each in proportion to the duration of the H(2)O(2) stimulation (P<0.05), but, in
      the equol-pretreated group, such decrease was not statistically significant.
      After Hoechst 33342 staining, in the equol-pretreated group the number of cells
      with apoptotic morphology decreased significantly. Equol pretreatment effectively
      inhibited the H(2)O(2)-induced cell death by the reduction of intracellular ROS
      production (P<0.05). Incubation of bAECs with equol increased the expression of
      phospho-p38 MAPK and Bcl-2 after the H(2)O(2) exposure compared with their
      expression without the equol pretreatment. Furthermore, SB203580 inhibited
      phospho-p38 MAPK expression and increased apoptotic cell death. This study proves
      equol has a significant antioxidant effect on the bAECs that were exposed to
      H(2)O(2).

PMID- 18708030
TI  - The effect of thiopurine drugs on DNA methylation in relation to TPMT expression.
AB  - The thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well
      established agents for the treatment of leukaemia but their main modes of action
      are controversial. Thiopurine methyltransferase (TPMT) metabolises thiopurine
      drugs and influences their cytotoxic activity. TPMT, like DNA methyltransferases
      (DNMTs), transfers methyl groups from S-adenosylmethionine (SAM) and generates S
      adenosylhomocysteine (SAH). Since SAM levels are dependent on de novo purine
      synthesis (DNPS) and the metabolic products of 6-TG and 6-MP differ in their
      ability to inhibit DNPS, we postulated that 6-TG compared to 6-MP would have
      differential effects on changes in SAM and SAH levels and global DNA methylation,
      depending on TPMT status. To test this hypothesis, we used a human embryonic
      kidney cell line with inducible TPMT. Although changes in SAM and SAH levels
      occurred with each drug, decrease in global DNA methylation more closely
      reflected a decrease in DNMT activity. Inhibition was influenced by TPMT for 6
      TG, but not 6-MP. The decrease in global methylation and DNMT activity with 6-MP,
      or with 6-TG when TPMT expression was low, were comparable to 5-aza-2'
      deoxycytidine. However, this was not reflected in changes in methylation at the
      level of an individual marker gene (MAGE1A). The results suggest that a non-TPMT
      metabolised metabolite of 6-MP and 6-TG and the TPMT-metabolised 6-MP metabolite
      6-methylthioguanosine 5'-monophosphate, contribute to a decrease in DNMT levels
      and global DNA methylation. As demethylating agents have shown promise in
      leukaemia treatment, inhibition of DNA methylation by the thiopurine drugs may
      contribute to their cytotoxic affects.

PMID- 18708031
TI  - Anoikis: a necessary death program for anchorage-dependent cells.
AB  - Cell to matrix adhesion is a key factor for cellular homeostasis and disruption
      of such interaction has adverse effects on cell survival. It leads to a specific
      type of apoptosis known as "anoikis" in most non-transformed cell types. This
      kind of apoptosis following loss of cell anchorage is important for development,
      tissue homeostasis and several diseases. Integrins sense mechanical forces
      arising from the matrix, thereby converting these stimuli to downstream signals
      modulating cell viability. Anchorage-independent growth is a crucial step during
      tumorigenesis and in particular during the metastatic spreading of cancer cells.
      The disruption of the tight control leading an "homeless" cell to death is
      therefore able to violate the cell defences against transformation. This review
      analyses the recent investigations into the molecular mechanisms governing
      anoikis, discussing the different ways in which adhesion can influence this
      process and addressing the relevance of this unique apoptosis mode in the
      development of metastatic cancers, as well as in other diseases.

PMID- 18708032
TI  - Wavelet analysis of the EEG during the neurocognitive evaluation of invalidly
      cued targets.
AB  - In a spatial central cueing paradigm, positions in the horizontal meridian were
      cued to evaluate the neurocognitive processing of validly (V) and invalidly cued
      (I) targets. ERPs were obtained from 20 EEG channel recordings. Complex Morlet
      wavelets were applied for computing event-related spectral power (ERSP)
      modulations and inter-trial phase coherence (ITC). P3a and P3b responses were
      increased in a statistically significant manner in I targets with regard to V
      targets. This increase seems to be generated only by phase resetting without
      enhancement of spectral power. Comparing ERSP modulations between I and V target
      trials we found a major effect centred in the alpha range. The following results
      were obtained for invalid condition in relation to valid condition: 6-12Hz ERSP
      decrease topographically widespread over the scalp, starting around 450 ms and
      peaking around 650 ms; 10-14Hz ERSP increase peaking around 200 ms at fronto
      central electrodes; and 10-14Hz ERSP decrease occurring from 400 to 600 ms at
      posterior electrodes. Therefore, the invalidity effect indeed produces salient
      changes in the stimulus related and ongoing neuronal activity leading to a brain
      state of comparative higher activity both excitatory and inhibitory with respect
      to the validly cued target processing.

PMID- 18708033
TI  - Alpha7 nicotinic acetylcholine receptor expression by vascular smooth muscle
      cells facilitates the deposition of Abeta peptides and promotes cerebrovascular
      amyloid angiopathy.
AB  - Deposition of beta-amyloid (Abeta) peptides in the walls of brain blood vessels,
      cerebral amyloid angiopathy (CAA), is common in patients with Alzheimer's disease
      (AD). Previous studies have demonstrated Abeta peptide deposition among vascular
      smooth muscle cells (VSMCs), but the source of the Abeta and basis for its
      selective deposition in VSMCs are unknown. In the present study, we examined the
      deposition patterns of Abeta peptides, Abeta40 and Abeta42, within the
      cerebrovasculature of AD and control patients using single- and double-label
      immunohistochemistry. Abeta40 and Abeta42 were abundant in VSMCs, especially in
      leptomeningeal arteries and their initial cortical branches; in later-stage AD
      brains this pattern extended into the microvasculature. Abeta peptide deposition
      was linked to loss of VSMC viability. Perivascular leak clouds of Abeta-positive
      material were associated primarily with arterioles. By contrast, control brains
      possessed far fewer Abeta42- and Abeta40-immunopositive blood vessels, with
      perivascular leak clouds of Abeta-immunopositive material rarely observed. We
      also demonstrate that VSMCs in brain blood vessels express the alpha7 nicotinic
      acetylcholine receptor (alpha7nAChR), which has high binding affinity for Abeta
      peptides, especially Abeta42. These results suggest that the blood and blood
      brain barrier permeability provide a major source of the Abeta peptides that
      gradually deposit in brain VSMCs, and the presence and abundance of the
      alpha7nAChR on VSMCs may facilitate the selective accumulation of Abeta peptides
      in these cells.

PMID- 18708035
TI  - Predominant localization of EFA6A, a guanine nucleotide exchange factor for ARF6,
      at the perisynaptic photoreceptor processes.
AB  - EFA6A is a guanine nucleotide exchange factor that is highly expressed in the
      nervous system with the ability to activate ADP ribosylation factor 6 (ARF6). In
      this study, we demonstrated the immunohistochemical localization of EFA6A in the
      adult mouse retina. Strong immunoreactivity for EFA6A was detected predominantly
      in the outer plexiform layer (OPL), where EFA6A was partially overlapped with
      dystrophin and synaptophysin. Immunoelectron microscopic analysis revealed that
      EFA6A was localized predominantly at the perisynaptic processes of photoreceptor
      terminals without association with synaptic ribbons. These findings suggest that
      EFA6A-ARF6 pathway may play a specific role at a subcompartment of perisynaptic
      photoreceptor processes.

PMID- 18708034
TI  - Very brief focal ischemia simulating transient ischemic attacks (TIAs) can injure
      brain and induce Hsp70 protein.
AB  - This study examined very brief focal ischemia that simulates transient ischemic
      attacks (TIAs) that occur in humans. Adult rats were subjected to sham operations
      or 5 min, 10 min, or 2 h of middle cerebral artery (MCA) ischemia using the
      suture (thread) model. Hsp70 protein was induced 24 h, 48 h and 72 h later in
      neurons throughout the entire MCA territory in many but not all animals.
      Following 5- and 10-minute MCA occlusions, 9 of 32 animals (28%) had
      microinfarcts mostly in dorsal lateral striatum. Uncommon Hsp70 stained
      intracellular cytoplasmic inclusions, some of which co-localized with activated
      caspase-3, were detected in microglia, macrophages, astrocytes and
      oligodendrocytes. Hsp70 stained neurons were TUNEL negative at 24 h and 48 h
      whereas some Hsp70 stained neurons were TUNEL positive at 72 h after reperfusion.
      Hsp70 positive, activated "bushy" microglia and Hsp70 negative, activated
      "polarized" or rod-shaped microglia were located outside of the microinfarcts.
      Thus, experimental focal ischemia simulating TIAs can: induce Hsp70 protein
      throughout the ischemic vessel territory; produce Hsp70 protein positive glial
      inclusions; activate Hsp70 positive and negative microglia; and cause
      microinfarcts in some animals.

PMID- 18708036
TI  - Antinociceptive effects of intracerebroventricular administration of guanine
      based purines in mice: evidences for the mechanism of action.
AB  - It is well known that adenine-based purines exert multiple effects on pain
      transmission. However, less attention has been given to the potential effects of
      guanine-based purines (GBPs) on pain transmission. The aim of this study was to
      investigate the effects of intracerebroventricular (i.c.v.) guanosine and GMP on
      mice pain models. Mice received an i.c.v. injection of vehicle (saline or 10 muM
      NaOH), guanosine (5 to 400 nmol), or GMP (240 to 960 nmol). Additional groups
      were also pre-treated with i.c.v. injection of the A(1)/A(2A) antagonist caffeine
      (15 nmol), the non-selective opioid antagonist naloxone (12.5 nmol), or the 5'
      nucleotidase inhibitor AOPCP (1 nmol). Measurements of CSF purine levels and
      cortical glutamate uptake were performed after treatments. Guanosine and GMP
      produced dose-dependent antinociceptive effects. Neither caffeine nor naloxone
      affected guanosine antinociception. Pre-treatment with AOPCP completely prevented
      GMP antinociception, indicating that conversion of GMP to guanosine is required
      for its antinociceptive effects. Intracerebroventricular administration of
      guanosine and GMP induced, respectively, a 180- and 1800-fold increase on CSF
      guanosine levels. Guanosine was able to prevent the decrease on cortical
      glutamate uptake induced by intraplantar capsaicin. This study provides new
      evidence on the mechanism of action of GBPs, with guanosine and GMP presenting
      antinociceptive effects in mice. This effect seems to be independent of adenosine
      and opioid receptors; it is, however, at least partially associated with
      modulation of the glutamatergic system by guanosine.

PMID- 18708037
TI  - SCA8 mRNA expression suggests an antisense regulation of KLHL1 and correlates to
      SCA8 pathology.
AB  - An increasing number of inherited neurodegenerative diseases are known to be
      caused by the expansion of unstable trinucleotide repeat tracts. Spinocerebellar
      ataxia type 8 (SCA8) has been identified as being partly caused by a CTG
      expansion in an untranslated, endogenous antisense RNA that overlaps the Kelch
      like 1 (KLHL1) gene. Clinically, SCA8 patients show similar features to those
      with the other SCAs, including limb and truncal ataxia, ataxic dysarthria and
      horizontal nystagmus, all of which are signs of dysfunction of the cerebellar
      system. However, allele sizes within the SCA8 proposed pathogenic range have been
      reported in patients with ataxia of unknown etiology, in individuals from
      pedigrees with other SCA or Friedreich's ataxia, and in patients with Alzheimer's
      disease, schizophrenia or parkinsonism. These observations suggest that mutation
      of the SCA8 locus might affect neurons other than the cerebellum. Antisense
      transcripts are known to regulate complementary sense transcripts and are
      involved in several biologic functions, such as development, adaptive response,
      and viral infection. In order to test whether SCA8 affects the KLHL1 expression
      by antisense RNA in brain cells, we examined the expression pattern of KLHL1 and
      SCA8 in human tissues and in mouse brain regions. SCA8 expression was colocalized
      with KLHL1 transcript in many brain regions whose functions are correlated to the
      clinical symptoms of SCA8 patients. These findings lead to the hypothesis of a
      possible relevance that SCA8 transcript downregulates KLHL1 expression through an
      antisense mechanism, which then leads to SCA8 neuropathogenesis.

PMID- 18708038
TI  - Time-course of neuronal death in the mouse pilocarpine model of chronic epilepsy
      using Fluoro-Jade C staining.
AB  - Epilepsy is a serious neurological disorder in human beings and the long-term
      pathological events remain largely obscure. We are interested in elucidating long
      term brain injury that may occur in the temporal lobe epilepsy, and time-course
      of neuronal death was examined in a mouse pilocarpine model of chronic epilepsy
      by Fluoro-Jade C (FJC) dye that can specifically stain the degenerative neurons
      in the central nervous system. The FJC stain combined with immunohistochemistry
      to neuronal nuclear specific protein revealed that pilocarpine-induced status
      epilepticus (SE) resulted in massive degenerative death of neuronal cells in
      brains with their dense distribution in the cerebral cortex and hippocampus. The
      FJC-positive degenerating neurons, most of them also expressed apoptosis
      signaling molecules such as caspase-9 and activated caspase-3, occurred at 4h,
      increased into peak levels at 12h-3d, and then gradually went down at 7d-14d
      after onset of SE. More interestingly, a large percentage (about 88%) of FJC
      positive degenerative neurons were GABAergic as indicated with their
      immunoreactivity to glutamic acid decarboxylase-67, implying that inhibitory
      function of GABAergic neural system might by seriously damaged in brains subject
      to SE attack in this mouse pilocarpine model. Taken together with previous
      studies, time-course of degenerative neurons in the mouse pilocarpine model by
      Fluoro-Jade C staining further benefits understanding of long-term brain
      pathological changes and recurrent seizure mechanism, and may also result in
      finding the most suitable time-window in therapeutic manipulation of the chronic
      epilepsy in human beings.

PMID- 18708039
TI  - Overexpression of N-WASP in the brain of human epilepsy.
AB  - Neuronal circuit remodeling is the most critical pathological characteristic
      closely associated with the initiation and maintenance of epilepsy; however, the
      exact mechanisms of neuronal remodeling need further elucidation. Neuronal
      Wiskott-Aldrich syndrome protein (N-WASP) is a key regulator of the actin
      cytoskeleton that causes actin polymerization and thus neurite extension. Our
      previous research demonstrated that the upstream regulator of N-WASP, cell
      division cycle 42 GTP-binding protein (Cdc42), is significantly upregulated in
      the brains of patients with intractable epilepsy (IE). In addition, cDNA
      microarray analysis has shown that gene expression of N-WASP is notably enhanced
      in the epileptic brain, suggesting a possible role for N-WASP in epileptogenesis.
      Here, we investigated the expression of N-WASP and its downstream effector, actin
      related protein 2/3 (Arp2/3), at the protein level in the temporal lobe of IE
      patient brains to explore its possible role in the genesis of IE. Forty surgical
      samples from brains of patients with IE and 20 control brain tissues were
      obtained for this study. The expression of N-WASP in the anterior temporal
      neocortex was detected using immunohistochemistry, immunofluorescence and western
      blotting; Arp2/3 expression was detected by western blotting. Compared with
      controls, N-WASP expression in brains of IE patients was significantly higher;
      similarly, Arp2/3 level was markedly increased in the IE patient group. These
      results suggest that increased expression of N-WASP in the human brain may be
      associated with human IE.

PMID- 18708040
TI  - Anti-proliferative and pro-apoptotic effect of CPT13, a novel camptothecin
      analog, on human colon cancer HCT8 cell line.
AB  - 10-(2-pyrazolyl-ethoxy)-(20S)-camptothecin (CPT13) is a novel semi-synthetic
      analogue of camptothecin, our previous report had shown that it possessed higher
      in vitro cytoxicity activity towards human colon cancer HCT8 cell line than
      topotecan. In this study, the anti-proliferative effect of CPT13 on HCT8 cell
      line in vitro was analyzed. In order to further explore the underlying mechanism
      of cell growth inhibition of CPT13 towards HCT8 cell line, the cell cycle
      distribution, apoptosis proportion, the nuclei morphological changes and caspase
      8 and caspase-3 activities were measured. Additionally the changes of
      mitochondrial morphology and membrane potential (DeltaPsim) were analyzed by
      atomic force microscopy (AFM) and flow cytometry, respectively. The results
      showed that CPT13 inhibited HCT8 cell growth by causing cell cycle arrest at G2/M
      transition and induced apoptosis, as evidenced by the typical apoptotic
      morphology such as condensation and fragmentation of nuclei and formation of
      apoptotic bodies. The changes of mitochondrial morphology, dose-dependently
      decrease in DeltaPsim and the enhancement of caspase-8 and caspase-3 activities
      were observed in different concentrations of drug treatment group. Our results
      suggest that CPT13 induces apoptosis by alternations of mitochondrial
      transmembrane depolarization, activation of caspase-8 and caspase-3. Therefore,
      CPT13 appears to be a potent drug against human colon cancer via induction of
      apoptosis and may be used as an alternative drug to therapy cancer.

PMID- 18708041
TI  - Determination of anti-neutrophil cytoplasmic antibodies in small vessel
      vasculitis: Comparative analysis of different strategies.
AB  - BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with
      primary small vessel vasculitis (SVV). Proteinase-3 (PR3)-ANCA are primarily
      associated with Wegener granulomatosis, whereas myeloperoxidase (MPO)-ANCA are
      primarily associated with microscopic polyangiitis (MPA) and vasculitic Churg
      Strauss syndrome. We evaluated whether a strategy that is based on screening with
      ELISA or fluoroenzymeimmunoassay (FEIA) is an accurate alternative to screening
      with indirect immunofluorescence (IIF). METHODS: C-ANCA and P-ANCA were
      determined by IIF and PR3-ANCA and MPO-ANCA were determined by ELISA (Inova) or
      FEIA (Phadia) on 326 patients (38 with newly diagnosed SVV and 288 diseased
      controls). RESULTS: Specificity and positive likelihood ratios were higher for
      ELISA and FEIA than for IIF. Post-test probability for SVV of a positive test
      result was higher for ELISA and FEIA than for IIF. Decision tree analysis in
      which several testing strategies were compared revealed that a testing strategy
      that is based on screening with ELISA or FEIA had an expected clinical utility
      that was comparable to screening with IIF and confirming with ELISA or FEIA. The
      highest expected clinical utility was found when both IIF and ELISA or FEIA were
      performed on all samples. CONCLUSIONS: A strategy based on screening for ANCA
      with ELISA or FEIA (without prior IIF) is a valuable alternative to screening
      with IIF and confirming with ELISA or FEIA.

PMID- 18708042
TI  - Alanine aminotransferase and gamma-glutamyl transferase are associated with the
      metabolic syndrome but not with angiographically determined coronary
      atherosclerosis.
AB  - BACKGROUND: Recently, elevated liver enzymes have attracted great interest as
      potential novel markers of cardiovascular risk. Their association with
      angiographically determined coronary artery disease (CAD) is unknown. METHODS: We
      enrolled 1000 consecutive patients undergoing coronary angiography for the
      evaluation of suspected or established stable CAD. The metabolic syndrome (MetS)
      was defined according to ATP-III criteria; significant CAD was diagnosed in the
      presence of coronary stenoses with lumen narrowing >or=50%. RESULTS: Serum
      alanine aminotransferase (ALT), the ALT/aspartate aminotransferase (AST) ratio,
      and serum gamma-glutamyl transferase (GGT) were significantly higher in patients
      with the MetS than in subjects without the MetS (34+/-21 vs. 29+/-20 U/l;
      p<0.001, 1.16+/-0.39 vs. 1.00+/-0.36 U/l, p<0.001; and 53+/-88 vs. 43+/-57 U/l,
      p=0.001, respectively) but were similar in patients with significant CAD as in
      those who did not have significant CAD at angiography (p=0.592; p=0.731, and
      p=0.716, respectively). Analysis of covariance after multivariate adjustment
      including alcohol consumption confirmed that ALT, ALT/AST ratio, and GGT were
      significantly and independently associated with the MetS but not with significant
      CAD. CONCLUSIONS: ALT, the ALT/AST ratio, and GGT are associated with the MetS
      but not with angiographically determined coronary atherosclerosis.

PMID- 18708043
TI  - The influence of smoking on semen quality, seminal microelements and Ca2+-ATPase
      activity among infertile and fertile men.
AB  - OBJECTIVE: Tobacco smoking is now increasing rapidly throughout the developing
      world and is one of the biggest threats to current and future world health.
      Several studies have addressed the role of cigarette smoking on semen quality,
      but the exact mechanisms remain inconclusive. In order to evaluate the
      detrimental effects of smoking on semen quality among Saudi subjects, the levels
      of different seminal parameters in smokers were compared to non-smokers. PATIENTS
      AND METHODS: A total of 159 semen samples (61 smokers and 98 non-smokers) from
      men attending an infertility clinic for routine infertility workup were sub
      grouped into fertile or infertile and were compared based on standard semen
      analysis (according to WHO guidelines), content of metals (magnesium, zinc and
      cadmium) and plasma membrane Ca(2+)-ATPase activity of sperms. RESULTS: Cadmium
      concentration was found significantly higher in smokers than in non-smokers
      either in fertile or infertile group (2.9+/-0.4 vs 1.4+/-0.7; 2.9+/-0.5 vs 1.3+/
      0.7 microg L(-1); respectively). Together with this increase in seminal Cd a
      significant decrease in Ca(2+)-ATPase activity (21.5+/-2.8 vs 33.71+/-1.2; 20.7+/
      1.5 vs 35.07+/-2.9 mmol min(-1) mg(-1) protein, p<0.05), decrease in seminal zinc
      (109.8+/-8.1 vs 189.7+/-9.9 mg L(-1), p<0.01) and decrease in sperm motility
      (41.9%+/-2.9 vs 46.01%+/-2.5; 9.8%+/-2.4 vs 15.3%+/-2.7, p<0.05) were found.
      CONCLUSION: Our data demonstrate that cigarette smoking affects both Ca(2+)
      ATPase activity and motility of the spermatozoa. These effects may be attributed
      to increased seminal cadmium and reduced zinc concentrations.

PMID- 18708044
TI  - Drosophila processing bodies in oogenesis.
AB  - Processing bodies (P-bodies) have emerged as important subcellular structures
      that are involved in mRNA metabolism. To date, a detailed description of P-bodies
      in Drosophila oogenesis is lacking. To this end, we first demonstrate that
      Drosophila decapping protein 2 (dDcp2) contains intrinsic decapping activity and
      its enzymatic activity was not detectably enhanced by Drosophila decapping
      protein 1 (dDcp1). dDcp1-containing bodies in the nurse cell cytoplasm can
      associate with the 5' to 3' exoribonuclease, Pacman in addition to dDcp2 and
      Me31B. The size and number of dDcp1 bodies are dynamic and dramatically increased
      in dDcp2 and pacman mutant backgrounds supporting the conclusion that dDcp1
      bodies in nurse cell cytoplasm are Drosophila P-bodies. In stage 2-6 oocytes,
      dDcp1 bodies appear to be distinct from previously characterized P-bodies since
      they are insensitive to cycloheximide and RNase A treatments. Curiously, dDcp2
      and Pacman do not colocalize with dDcp1 at the posterior end of the oocyte in
      stage 9-10 oocytes. This suggests that dDcp1 bodies are in a developmentally
      distinct state separate from the 5' end mRNA degradation enzymes at later stages
      in the oocyte. Interestingly, re-formation of maternally expressed dDcp1 with
      dDcp2 and Pacman was observed in early embryogenesis. With respect to
      developmental switching, the maternal dDcp1 is proposed to serve as a marker for
      the re-formation of P-bodies in early embryos. This also suggests that a
      regulated conversion occurs between maternal RNA granules and P-bodies from
      oogenesis to embryogenesis.

PMID- 18708045
TI  - Cad74A is regulated by BR and is required for robust dorsal appendage formation
      in Drosophila oogenesis.
AB  - Drosophila egg development is an established model for studying epithelial
      patterning and morphogenesis, but the connection between signaling pathways and
      egg morphology is still incompletely understood. We have identified a non
      classical cadherin, Cad74A, as a putative adhesion gene that bridges epithelial
      patterning and morphogenesis in the follicle cells. Starting in mid-oogenesis,
      Cad74A is expressed in the follicle cells that contact the oocyte, including the
      border cells and most of the columnar follicle cells. However, Cad74A is
      repressed in two dorsolateral patches of follicle cells, which participate in the
      formation of tubular respiratory appendages. We show genetically that Cad74A is
      downstream of the EGFR and BMP signaling pathways and is repressed by the Zn
      finger transcription factor Broad. The correlation of Cad74A repression in the
      cells that bend out of the plane of the follicular epithelium is preserved across
      Drosophila species and mutant backgrounds exhibiting a range of eggshell
      phenotypes. Complete removal of Cad74A from the follicle cells causes defects in
      dorsal appendage formation. Ectopic expression of Cad74A in the roof cells
      results in shortened, flattened appendages due to the hindered migration of the
      roof cells. Based on these results, we propose that Cad74A is part of the
      adhesive machinery that enables robust dorsal appendage formation, and as such
      provides a link between the patterning of the follicle cells and eggshell
      morphogenesis.

PMID- 18708046
TI  - Isobolographic and behavioral characterizations of interactions between
      vigabatrin and gabapentin in two experimental models of epilepsy.
AB  - The aim of this study was to characterize the pharmacodynamic, pharmacokinetic
      and adverse-effect profiles of vigabatrin and gabapentin. Isobolographic analysis
      was used in two mouse experimental models of epilepsy: the maximal electroshock
      seizure threshold test and pentylenetetrazole-induced seizures. In the maximal
      electroshock seizure threshold test, electroconvulsions were produced by a
      current with various intensities whilst in the pentylenetetrazole test a CD(97)
      dose (100 mg/kg) was used. Potential adverse-effect profiles of interactions of
      vigabatrin with gabapentin at three fixed-ratios of 1:3, 1:1 and 3:1 from both
      seizure tests were evaluated in the chimney (motor performance) and grip-strength
      (skeletal muscular strength) tests. Vigabatrin and gabapentin total brain
      concentrations were determined with high performance liquid chromatography.
      Vigabatrin and gabapentin administered singly increased the electroconvulsive
      threshold (TID(20) - 226.2 and 70.0 mg/kg, respectively). With isobolography, the
      combination of vigabatrin with gabapentin at the fixed-ratio of 1:3 exerted supra
      additive (synergistic) interactions whilst at 1:1 and 3:1 additivity occurred.
      Similarly, vigabatrin and gabapentin administered singly suppressed the
      pentylenetetrazole-induced seizures (ED(50) values - 622.5 and 201.1 mg/kg,
      respectively). Isobolography revealed that vigabatrin with gabapentin in
      combination at the fixed-ratio of 1:1 produced supra-additive (synergistic)
      interaction whilst at 1:3 and 3:1 additivity occurred. In combination neither
      motor coordination nor skeletal muscular strength was affected. Total vigabatrin
      and gabapentin brain concentrations revealed that neither drug affected the
      pharmacokinetics of the other. Vigabatrin and gabapentin have a favorable
      pharmacodynamic interaction in animal seizure models in the absence of acute
      adverse effects or concurrent pharmacokinetic changes.

PMID- 18708047
TI  - Antinociceptive property of intrathecal and intraperitoneal administration of a
      novel water-soluble isoindolin-1-one derivative, JM 1232 (-) in rats.
AB  - Antinociceptive effects of a new water-soluble sedative agent, an isoindolin-1
      one derivative, (-)-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-phenyl-3,5,6,7
      tetrahydrocyclopenta[f]isoindol-1-(2H)-one (JM 1232 (-)) were studied in two
      different nociceptive models of rats. Sprague-Dawley rats with lumbar intrathecal
      catheters were tested for their thermal tail withdrawal response and for their
      paw flinches by formalin injection after intrathecal administration of various
      doses of JM 1232 (-). The effects of intraperitoneal administration were also
      investigated. In addition, behavioral side effects were examined. When
      antinociceptive effects were observed, the effects of pretreatment with
      flumazenil or naloxone for the maximum effective dose were evaluated. Eight rats
      were used in each dose of each group. Intrathecal JM 1232 (-) increased the tail
      flick latency and decreased the number of flinches in both phases 1 and 2 of the
      formalin test. These changes were antagonized by intrathecal flumazenil but not
      by naloxone. Intraperitoneal JM 1232 (-) had no effects on the tail flick
      latency, but decreased the number of flinches in both phases 1 and 2 of the
      formalin test. The latter was antagonized by intraperitoneal flumazenil and
      naloxone with bigger effects of flumazenil. Intraperitoneal JM 1232 (-) 3000
      microg induced reversible motor disturbance. In conclusion, intrathecal JM 1232 (
      ) exerts antinociceptive effects on acute thermal and inflammatory stimuli
      through benzodiazepine-GABA(A) receptors in the spinal cord. Intraperitoneal JM
      1232 (-) was antinociceptive only against inflammatory stimulus and this is
      mediated mainly by benzodiazepine-GABA(A) receptors, but partially by micro
      opioid receptors in the brain.

PMID- 18708048
TI  - Lymphatic-specific expression of dipeptidyl peptidase IV and its dual role in
      lymphatic endothelial function.
AB  - Lymphatic vessels play an important role in the maintenance of tissue fluid
      homeostasis and in the transport of immune cells to lymph nodes, but they also
      serve as the major conduit for cancer metastasis to regional lymph nodes.
      However, the molecular mechanisms regulating these functions are poorly
      understood. Based on transcriptional profiling studies of cultured human dermal
      lymphatic (LEC) versus blood vascular endothelial cells (BEC), we found that
      dipeptidyl peptidase IV (DPPIV) mRNA and protein are much more strongly expressed
      by cultured lymphatic endothelium than by blood vascular endothelium that only
      expressed low levels of DPPIV in culture. The enzymatic cleavage activity of
      DPPIV was significantly higher in cultured LEC than in BEC. Differential
      immunofluorescence analyses of human organ tissue microarrays for DPPIV and
      several vascular lineage-specific markers revealed that DPPIV is also
      specifically expressed in situ by lymphatic vessels of the skin, esophagus, small
      intestine, breast and ovary. Moreover, siRNA-mediated DPPIV knockdown inhibited
      LEC adhesion to collagen type I and to fibronectin, and also reduced cell
      migration and formation of tube-like structures. These results identify DPPIV as
      a novel lymphatic marker and mediator of lymphatic endothelial cell functions.

PMID- 18708049
TI  - Oncogenic Ras-transformed human fibroblasts exhibit differential changes in
      contraction and migration in 3D collagen matrices.
AB  - Tractional force exerted by tissue cells in 3D collagen matrices can be utilized
      for matrix remodeling or cell migration. The interrelationship between these
      motile processes is not well understood. The current studies were carried out to
      test the consequences of oncogenic Ras (H-Ras(V12)) transformation on human
      fibroblast contraction and migration in 3D collagen matrices. Beginning with
      hTERT-immortalized cells, we prepared fibroblasts stably transformed with E6/E7
      and with the combination HPV16 E6/E7 and H-Ras(V12). Oncogenic Ras-transformed
      cells lost contact inhibition of cell growth, formed colonies in soft agar and
      were unable to make adherens junctions. We observed no changes in the extent or
      growth factor dependence of collagen matrix contraction (floating or stress
      relaxation) by oncogenic Ras-transformed cells. On the other hand, transformed
      cells in nested collagen matrices lost not only growth factor selectivity, but
      also cell-matrix density-dependent inhibition of migration. These findings
      demonstrate differential regulation of collagen matrix contraction and cell
      migration in 3D collagen matrices.

PMID- 18708050
TI  - HB-EGF: a unique mediator of embryo-uterine interactions during implantation.
AB  - An implantation-competent blastocyst, several hours prior to its attachment on
      the uterine wall, transmits signals to surrounding uterine cells and vice-versa
      to initiate a two-way interaction. The language of this precocious dialogue is
      versatile, taking advantage of secreted molecules for long-range interactions and
      membrane-bound molecules for more immediate interactions. Heparin-binding
      epidermal growth factor-like growth factor (HB-EGF) was identified as an early
      messenger of implantation which uses both modes of communication. In this review,
      we discuss the footprint of HB-EGF as to how it was initially identified as a
      mediator of implantation and how it initiates embryo-uterine interactions during
      this process.

PMID- 18708051
TI  - Pulsatility of parafoveal capillary leukocytes.
AB  - The use of adaptive optics (AO) in a confocal scanning laser ophthalmoscope
      (AOSLO) allows for long-term imaging of parafoveal capillary leukocyte movement
      and measurement of leukocyte velocity without contrast dyes. We applied the AOSLO
      to investigate the possible role of the cardiac cycle on capillary leukocyte
      velocity by directly measuring capillary leukocyte pulsatility. The parafoveal
      regions of 8 eight normal healthy subjects with clear ocular media were imaged
      with an AOSLO. All subjects were dilated and cyclopleged. The AOSLO field of view
      was either 1.4x1.5 degrees or 2.35x2.5 degrees, the imaging wavelength was 532 nm
      and the frame rate was 30fps. A photoplethysmograph was used to record the
      subject's pulse synchronously with each AOSLO video. Parafoveal capillary
      leukocyte velocities and pulsatility were determined for two or three capillaries
      per subject. Leukocyte velocity and pulsatility were determined for all eight
      subjects. The mean parafoveal capillary leukocyte velocity for all subjects was
      V(mean)=1.30 mm/s (SD=+/-0.40 mm/s). There was a statistically significant
      difference between leukocyte velocities, V(max) and V(min), over the pulse cycle
      for each subject (p<0.05). The mean pulsatility was P(mean)=0.45 (+/-0.09).
      Parafoveal capillary leukocyte pulsatility can be directly and non-invasively
      measured without the use of contrast dyes using an AOSLO. A substantial amount of
      the variation found in leukocyte velocity is due to the pulsatility that is
      induced by the cardiac cycle. By controlling for the variation in leukocyte
      velocity caused by the cardiac cycle, we can better detect other changes in
      retinal leukocyte velocity induced by disease or pharmaceutical agents.

PMID- 18708052
TI  - Striatal-enriched protein tyrosine phosphatase regulates dopaminergic neuronal
      development via extracellular signal-regulated kinase signaling.
AB  - The striatal-enriched protein tyrosine phosphatase (STEP) is highly expressed
      within dopaminoceptive neurons, suggesting the possibility that STEP may interact
      with dopaminergic signaling. We have previously shown that signaling through
      dopamine D2 receptor (D2R)-mediated extracellular signal-regulated kinase (ERK)
      activation plays a critical role in mesencephalic dopaminergic neuronal
      development. Here, we investigate the role of STEP in D2R-mediated ERK signaling,
      especially in dopaminergic neuronal development. Analyses of developmental
      expression of STEP and tyrosine hydroxylase (TH) in mouse brain demonstrate that
      STEP- and TH-positive cells are co-localized in the substantia nigra compacta of
      brains of postnatal 8-day-old mice, displaying STEP expression in dopaminergic
      neurons at this stage. Stereological analysis demonstrates a dynamic change in
      the number of STEP-expressing cells from midbrain to striatum during development
      in WT mice and significantly decreased number of STEP-expressing cells in mice
      lacking D2R (D2R(-/-) mice). The knockdown of STEP expression by treatment with
      oligomeric STEP siRNA significantly decreased the number of mesencephalic TH
      cells and inhibited D2R-mediated development of dopaminergic neurons on primary
      mesencephalic culture from WT mice, but not in primary cultures from D2R(-/-)
      mice. Furthermore, knockdown of STEP expression perturbed D2R-mediated ERK
      signaling in dopaminergic neuronal cells from WT mice, but not from D2R(-/-)
      mice. These results suggest that STEP is an important mediator in the dopamine
      D2R-mediated activation of ERK signaling and in the regulation of dopaminergic
      neuronal development.

PMID- 18708053
TI  - Gliopathy ensures persistent inflammation and chronic pain after spinal cord
      injury.
AB  - Research focused on improving recovery of function, including the reduction of
      central neuropathic pain (CNP) after spinal cord injury (SCI) is essential. After
      SCI, regional neuropathic pain syndromes above, at and below the level or spinal
      injury develop and are thought to have different mechanisms, but may share common
      dysfunctional glial mechanisms. Detloff et al., [Detloff, M.R., Fisher, L.C.,
      McGaughy, V., Longbrake, E.E., Popovich, P.G., Basso, D.M., Remote activation of
      microglia and pro-inflammatory cytokines predict the onset and severity of below
      level neuropathic pain after spinal cord injury in rats. Exp. Neurol. (2008),
      doi: 10.1016/j.expneurol.2008.04.009.] describe events in the lumbar region of
      the spinal cord after a midthoracic SCI injury, the so called "below-level" pain
      and compares the findings to peripheral nerve lesion findings. This commentary
      briefly reviews glial contributions and intracellular signaling mechanisms, both
      neuronal and glial, that provide the substrate for CNP after SCI, including the
      persistent glial production of factors that can maintain sensitization of dorsal
      horn neurons in segments remote from the spinal injury; ie. dorsal horn
      hyperexcitability to formerly non noxious stimuli that become noxious after SCI
      resulting in allodynia. The term "gliopathy" is proposed to describe the
      dysfunctional and maladaptive response of glial cells, specifically astrocytes
      and microglia, to neural injury that is initiated by the sudden injury induced
      increase in extracellular concentrations of glutamate and concomitant production
      of several proinflammatory molecules. It is important to understand the roles
      that different glia play in "gliopathy", a condition that appears to persist
      after SCI. Furthermore, targeted treatment of gliopathy will attenuate mechanical
      allodynia in both central and peripheral neuropathic pain syndromes.

PMID- 18708054
TI  - Wnt4 and Wnt5a promote adipocyte differentiation.
AB  - The roles of the non-canonical Wnt pathway during adipogenesis are not well
      known, though Wnt10b is known to function as a negative regulator for
      adipogenesis by activating the canonical Wnt pathway. We focused on the roles of
      Wnt4, Wnt5a and Wnt6, which are thought to be part of the non-canonical Wnt
      pathway. The expression of these genes changed dramatically at the initial stage
      of adipogenesis. Furthermore, the inhibition of Wnt4 or Wnt5a expression
      prevented the accumulation of triacylglycerol and decreased the expression of
      adipogenesis-related genes. Wnt4 and Wnt5a have crucial roles in adipogenesis as
      positive regulators.

PMID- 18708055
TI  - Arsenic trioxide stimulates SUMO-2/3 modification leading to RNF4-dependent
      proteolytic targeting of PML.
AB  - We have recently reported that poly-SUMO-2/3 conjugates are subject to a
      ubiquitin-dependent proteolytic control in human cells. Here we show that arsenic
      trioxide (ATO) increases SUMO-2/3 modification of promyelocytic leukemia (PML)
      leading to its subsequent ubiquitylation in vivo. The SUMO-binding ubiquitin
      ligase RNF4 mediates this modification and causes disruption of PML nuclear
      bodies upon treatment with ATO. Reconstitution of SUMO-dependent ubiquitylation
      of PML by RNF4 in vitro and in a yeast trans vivo system revealed a preference of
      RNF4 for chain forming SUMOs. Polysumoylation of PML in response to ATO thus
      leads to its recognition and ubiquitylation by RNF4.

PMID- 18708056
TI  - Mammalian BiP controls posttranslational ER translocation of the hepatitis B
      virus large envelope protein.
AB  - The hepatitis B virus L protein forms a dual topology in the endoplasmic
      reticulum (ER) via a process involving cotranslational membrane integration and
      subsequent posttranslational translocation of its preS subdomain. Here, we show
      that preS posttranslocation depends on the action of the ER chaperone BiP. To
      modulate the in vivo BiP activity, we designed an approach based on
      overexpressing its positive and negative regulators, ER-localized DnaJ-domain
      containing protein 4 (ERdj4) and BiP-associated protein (BAP), respectively. The
      feasibility of this approach was confirmed by demonstrating that BAP, but not
      ERdj4, destabilizes the L/BiP complex. Overexpressing BAP or ERdj4 inhibits preS
      posttranslocation as does the reduction of ATP levels. These results hint to a
      new role of BiP in guiding posttranslational polypeptide import into the
      mammalian ER.

PMID- 18708057
TI  - hOLFML1, a novel secreted glycoprotein, enhances the proliferation of human
      cancer cell lines in vitro.
AB  - We describe a novel secreted protein, named hOLFML1 (human olfactomedin-like
      protein 1), with an olfectamine domain in its C-terminus, mainly expressed in the
      small intestine, liver, lung and heart. Immunohistochemical staining on human
      small intestine indicated that the protein localizes preferentially in the
      intestinal villi. Interestingly, ectopic hOLFML1 promoted proliferation of HeLa
      cells and increased the percentage of cells in S phase. In contrast, knock down
      of hOLFML1 protein expression by siRNA inhibited cell proliferation and delayed
      the entry of cells into S phase. Our data also revealed that hOLFML1 is N
      glycosylated and its secretion is triggered by serum. Taken together, these
      findings suggest that hOLFML1 may play a significant role in the regulation of
      cell proliferation in vitro.

PMID- 18708058
TI  - Selective repression of YKL-40 by NF-kappaB in glioma cell lines involves
      recruitment of histone deacetylase-1 and -2.
AB  - Here we show that in contrast to other cancer types, tumor necrosis factor (TNF)
      alpha suppresses YKL-40 expression in glioma cell lines in a nuclear factor
      kappaB (NF-kappaB) dependent manner. Even though TNF-alpha causes recruitment of
      p65 and p50 subunits of NF-kappaB to the YKL-40 promoter in all cell types,
      recruitment of histone deacetylases (HDAC)-1 and -2, and a consequent
      deacetylation of histone H3 at the YKL-40 promoter occurs only in glioma cells.
      Importantly, using chromatin immunoprecipitation assays in frozen glioblastoma
      multiforme tissues, we show that YKL-40 levels decrease consistent with HDAC1
      recruitment despite high levels of nuclear p-p65. This study presents a paradigm
      for NF-kappaB regulation of one of its targets in a strict cell type specific
      manner.

PMID- 18708059
TI  - Cyclophilin-40 has a cellular role in the aryl hydrocarbon receptor signaling.
AB  - Cyclophilin-40 (CyP40) promotes the formation of the gel shift complex that
      contains the aryl hydrocarbon receptor (AhR), AhR nuclear translocator (Arnt) and
      dioxin response element (DRE) using baculovirus expressed proteins. Here we
      reported that CyP40 plays a role in the AhR signaling. When the CyP40 content in
      MCF-7 cells is reduced, up-regulation of cyp1a1 and cyp1b1 by 3
      methylchloranthrene (3MC) is also reduced, suggesting that CyP40 is essential for
      maximal AhR function. The CyP40 region containing amino acids 186-215, but not
      the peptidyl-prolyl cis-trans isomerase and tetratricopeptide repeat domains, is
      essential for forming the AhR/Arnt/DRE complex. CyP40 is found in the cell
      nucleus after 3MC treatment and appears to promote the DRE binding form of the
      AhR/Arnt heterodimer.

PMID- 18708060
TI  - Gonadal modulation of in vitro steroidogenic properties of dispersed
      adrenocortical cells from Sceloporus lizards.
AB  - Effects of adrenal corticosteroids on reproductive and endocrine functions of the
      gonads are well known, but reciprocal effects of gonadal hormones on the
      hypothalamo-pituitary-adrenal (HPA) axis and on adrenocortical steroidogenesis in
      particular have received much less attention. We investigated effects of
      gonadectomy and testosterone (T) replacement on adrenocortical cell function in a
      year-long field study of male Sceloporus undulatus (Eastern Fence Lizard) and in
      a shorter term laboratory study with male Sceloporus jarrovii (Yarrow's Spiny
      Lizard). We also compared females to males in Sceloporus virgatus (Striped
      Plateau Lizard) and investigated effects of gonadectomy in short-term laboratory
      experiment on females of this species. As measured by in vitro production of
      progesterone (P(4)), corticosterone (B), and aldosterone (ALDO), sensitivity of
      adrenocortical cells to corticotrophin (ACTH) was lower in control males than
      females of S. virgatus. In S. jarrovii males, cellular sensitivity to ACTH was
      reduced by orchiectomy but was not restored to levels of intact controls by T
      replacement. By contrast, in S. undulatus, cellular sensitivity to ACTH was not
      affected by orchiectomy alone but was reduced by T replacement in orchiectomized
      males. Maximal rates of steroid production were less consistently affected by
      experimental treatments, but were lower in males than in females of S. virgatus
      and were dramatically reduced by T replacement in orchiectomized S. undulatus
      males. Overall, our experiments clearly demonstrate two distinct sources of
      variation in functional capacities of dispersed adrenocortical cells isolated
      from Sceloporus lizards: (1) naturally occurring differences between males and
      females (Carsia and John-Alder, 2003), and (2) species-dependent changes in
      response to surgical gonadectomy with or without exogenous testosterone. Sex
      differences and functional lability in adrenocortical cells are probably
      widespread among vertebrates and may be an important component of variation in
      output of the HPA.

PMID- 18708061
TI  - Identification, expression and characterisation of a major salivary allergen (Cul
      s 1) of the biting midge Culicoides sonorensis relevant for summer eczema in
      horses.
AB  - Salivary proteins of Culicoides biting midges are thought to play a key role in
      summer eczema (SE), a seasonal recurrent allergic dermatitis in horses. The
      present study describes the identification, expression and clinical relevance of
      a candidate allergen of the North American midge Culicoides sonorensis.
      Immunoblot analysis of midge saliva revealed a 66 kDa protein (Cul s 1) that was
      bound by IgE from several SE-affected (SE+) horses. Further characterisation by
      fragmentation, mass spectrometry and bioinformatics identified Cul s 1 as
      maltase, an enzyme involved in sugar meal digestion. A cDNA encoding Cul s 1 was
      isolated and expressed as a polyhistidine-tagged fusion protein in a
      baculovirus/insect cell expression system. The clinical relevance of the affinity
      purified recombinant Cul s 1 (rCul s 1) was investigated by immunoblotting,
      histamine release testing (HRT) and intradermal testing (IDT) in eight SE+ and
      eight control horses. Seven SE+ horses had rCul s 1-specific IgE, whereas only
      one control animal had IgE directed against this allergen. Furthermore, the HRT
      showed rCul s 1 induced basophil degranulation in samples from seven of eight SE+
      horses but in none of the control animals. rCul s 1 also induced immediate (7/8),
      late-phase (8/8) and delayed (1/8) skin reactivity in IDT on all SE+ horses that
      had a positive test with the whole body extract (WBE) of C. sonorensis. None of
      the control horses showed immediate or delayed skin reactivity with rCul s 1, and
      only one control horse had a positive late-phase response, while several non
      specific late-phase reactions were observed with the insect WBE. Thus, we believe
      rCul s 1 is the first specific salivary allergen of C. sonorensis to be described
      that promises to advance both in vitro and in vivo diagnosis and may contribute
      to the development of immunotherapy for SE in horses.

PMID- 18708062
TI  - Immune depression induced by acanthocephalan parasites in their intermediate
      crustacean host: consequences for the risk of super-infection and links with host
      behavioural manipulation.
AB  - Parasite survival in hosts mainly depends on the capacity to circumvent the host
      immune response. Acanthocephalan infections in gammarids are linked with
      decreased activity of the prophenoloxidase (ProPO) system, suggesting an active
      immunosuppression process. Nevertheless, experimental evidence for this
      hypothesis is lacking: whether these parasites affect several immune pathways is
      unknown and the consequences of such immune change have not been investigated. In
      particular, the consequences for other pathogens are not known; neither are the
      links with other parasite-induced manipulations of the host. Firstly, using
      experimental infections of Pomphorhynchus laevis we confirmed that the lower
      immune activity in parasitised Gammarus pulex is induced by the parasite
      infection. Second, using natural infections of three different parasites, P.
      laevis, Pomphorhynchus tereticollis and Polymorphus minutus, we showed that
      acanthocephalan infection was associated with reduction of the activity of the
      ProPO system and the haemocyte concentration (two major parameters of crustacean
      immunity) suggesting that immune depression is a phenomenon affecting several
      immunological activities. This was confirmed by the fact that acanthocephalan
      infection (whatever the parasite species) was linked to a lower efficiency to
      eliminate a bacterial infection. The result suggests a cost of parasite immune
      depression. Finally, acanthocephalans are also known to induce behavioural
      alterations in the intermediate host which favour their transmission to
      definitive hosts. We did not find any correlation between behavioural and
      immunological alterations in both experimentally and naturally-infected
      gammarids. Overall, this study suggests that whilst immune depression might be
      beneficial to acanthocephalan survival within the intermediate gammarid host, it
      might also be costly if it increases host mortality to additional infections
      before transmission of the parasite.

PMID- 18708064
TI  - Parasite age-intensity relationships in red-spotted newts: does immune memory
      influence salamander disease dynamics?
AB  - Acquired immune memory in vertebrates influences transmission and persistence of
      infections, with consequences for parasite dynamics at both the individual and
      population levels. The potential impact of acquired immunity is of particular
      interest for salamanders, whose acquired immune systems are thought to be less
      effective than those of frogs and other tetrapods. One way to examine the
      importance of acquired immunity to parasite dynamics at the population level is
      by examining the relationship between host age and parasite infection intensity.
      Acquired immunity reduces infection rates in older animals, causing decreased
      parasite intensity in older age classes and leading to curvilinear age-intensity
      relationships for persistent parasites and convex age-intensity relationships for
      transient parasites. We used age-intensity relationships to look for the
      signature of acquired immunity for 12 parasite taxa of red-spotted newts
      (Notophthalmus viridescens), using data from a 2-year parasitological survey of
      six newt populations. We estimated ages from snout-vent length (SVL) based on the
      relationship between SVL and skeletochronologically-derived ages in a subset of
      newts. We found evidence of acquired immunity to two parasite taxa, bacterial
      pathogens and the protist Amphibiocystidium viridescens, whose convex age
      intensity relationships could not be easily explained by alternative mechanisms.
      Our results suggest that the acquired immune response of newts is sufficient to
      influence the dynamics of at least some parasites.

PMID- 18708063
TI  - The functional expression and characterisation of a cysteine peptidase from the
      invasive stage of the neuropathogenic schistosome Trichobilharzia regenti.
AB  - A transcriptional product of a gene encoding cathepsin B-like peptidase in the
      bird schistosome Trichobilharzia regenti was identified and cloned. The enzyme
      was named TrCB2 due to its 77% sequence similarity to cathepsin B2 from the
      important human parasite Schistosoma mansoni. The zymogen was expressed in the
      methylotropic yeast Pichia pastoris; procathepsin B2 underwent self-processing in
      yeast media. The peptidolytic activity of the recombinant enzyme was
      characterised using synthetic fluorogenic peptide substrates at optimal pH 6.0.
      Functional studies using different specific inhibitors proved the typical
      cathepsin B-like nature of the enzyme. The S(2) subsite specificity profile of
      recombinant TrCB2 was obtained. Using monospecific antibodies against the
      recombinant enzyme, the presence of cathepsin B2 was confirmed in extracts from
      cercariae (infective stage) and schistosomula (early post-cercarial stage) of T.
      regenti on Western blots. Also, cross-reactivity was observed between T. regenti
      and S. mansoni cathepsins B2 in extracts of cercariae, schistosomula or adults.
      In T. regenti, the antisera localised the enzyme to post-acetabular penetration
      glands of cercariae implying an important role in the penetration of host skin.
      The ability of recombinant TrCB2 to degrade skin, serum and nervous tissue
      proteins was evident. Elastinolytic activity suggests that the enzyme might
      functionally substitute the histolytic role of the serine class elastase known
      from S. mansoni and Schistosoma haematobium but not found in Schistosoma
      japonicum or in bird schistosomes.

PMID- 18708065
TI  - Hosts and habitats of Trichinella spiralis and Trichinella britovi in Europe.
AB  - Trichinella spiralis and Trichinella britovi are the two most common species of
      Trichinella circulating in Europe. Based on data provided to the International
      Trichinella Reference Centre over the past 20 years (data referring to 540
      isolates of T. spiralis and 776 isolates of T. britovi), we describe the host
      species and habitat characteristics for these two pathogens in Europe. A
      Geographical Information System was constructed using administrative boundaries,
      a Corine Land Cover (CLC) map, and an elevation map. In most countries, T.
      britovi is more widespread (62.5-100% of the isolates) than T. spiralis (0.0
      37.5%), although in Finland, Germany, Poland and Spain, T. spiralis is more
      prevalent (56.3-84.2% of the isolates). Trichinella britovi is more widespread
      than T. spiralis in sylvatic carnivores (89% versus 11%), whereas T. spiralis is
      prevalent in both wild boars (62% versus 38%) and domestic swine (82% versus
      18%), as well as in rodents (75% versus 25%). Trichinella spiralis and T. britovi
      circulate in the same environments: 41.1% and 46.0%, respectively, in
      agricultural areas, and 45.5% and 46.6% in forested and semi-natural areas.
      Although both pathogens can be transmitted by domestic and sylvatic cycles, their
      epidemiology is strongly influenced by the higher adaptability of T. spiralis to
      swine and of T. britovi to carnivores. These results are important because they
      include information on the countries at risk for these pathogens, the role played
      by specific species as reservoirs, the role of the pathogens in domestic and
      sylvatic cycles, and the role of the habitat in their circulation. The results
      can also be used to identify the most suitable animal species for the monitoring
      of these pathogens in Europe.

PMID- 18708066
TI  - Increased expression of ABC transport proteins is associated with ivermectin
      resistance in the model nematode Caenorhabditis elegans.
AB  - Widespread resistance to chemotherapeutic agents is one of the biggest challenges
      facing human health and the agricultural industry, with resistance to all current
      anthelmintics now recorded and few new agents or vaccines available.
      Understanding the development of drug resistance in parasitic nematodes is
      critical to prolonging the efficacy of current anthelmintics, developing markers
      for monitoring drug resistance and is beneficial in the design of new
      chemotherapeutic agents or targets. This study describes the development of
      ivermectin-resistant strains of the model nematode Caenorhabditis elegans through
      step-wise exposure to increasing doses of ivermectin commencing with a non-toxic
      dose of 1 ng/ml. Resistant strains were developed that displayed a multidrug
      resistance phenotype with cross-resistance to the related drug moxidectin and to
      other anthelmintics, levamisole and pyrantel, but not albendazole. Resistance was
      associated with increased expression of the multidrug resistance proteins (MRPs)
      and P-glycoproteins. Resistance to ivermectin was reversible by the co
      administration of MRP, P-glycoprotein and glutathione biosynthesis inhibitors,
      confirming the involvement of these proteins in resistance. In our model,
      resistance to low levels of ivermectin (<or=6 ng/ml) was associated with
      increased expression of mrp-1 and pgp-1 and decreased glutathione, while higher
      level resistance (10 ng/ml) was primarily associated with the increased
      expression of P-glycoproteins. Importantly, resistance was stable after 3 months
      without ivermectin treatment. This clearly demonstrates the involvement of
      transport proteins in ivermectin resistance and provides a model to understand
      drug resistance and its reversal.

PMID- 18708068
TI  - Kinetic coupling of folding and prolyl isomerization of beta2-microglobulin
      studied by mutational analysis.
AB  - Beta(2)-microglobulin (beta2-m), a protein responsible for dialysis-related
      amyloidosis, adopts a typical immunoglobulin domain fold with the N-terminal
      peptide bond of Pro32 in a cis isomer. The refolding of beta2-m is limited by the
      slow trans-to-cis isomerization of Pro32, implying that intermediates with a non
      native trans-Pro32 isomer are precursors for the formation of amyloid fibrils. To
      obtain further insight into the Pro-limited folding of beta2-m, we studied the
      Gdn-HCl-dependent unfolding/refolding kinetics using two mutants (W39 and P32V
      beta2-ms) as well as the wild-type beta2-m. W39 beta2-m is a triple mutant in
      which both of the authentic Trp residues (Trp60 and Trp95) are replaced by Phe
      and a buried Trp common to other immunoglobulin domains is introduced at the
      position of Leu39 (i.e., L39W/W60F/W95F). W39 beta2-m exhibits a dramatic
      quenching of fluorescence upon folding, enabling a detailed analysis of Pro
      limited unfolding/refolding. On the other hand, P32V beta2-m is a mutant in which
      Pro32 is replaced by Val, useful for probing the kinetic role of the trans-to-cis
      isomerization of Pro32. A comparative analysis of the unfolding/refolding
      kinetics of these mutants including three types of double-jump experiments
      revealed the prolyl isomerization to be coupled with the conformational
      transitions, leading to apparently unusual kinetics, particularly for the
      unfolding. We suggest that careful consideration of the kinetic coupling of
      unfolding/refolding and prolyl isomerization, which has tended to be neglected in
      recent studies, is essential for clarifying the mechanism of protein folding and,
      moreover, its biological significance.

PMID- 18708067
TI  - Evidence against involvement of aquaporin-4 in cell-cell adhesion.
AB  - Aquaporin-4 (AQP4) water channels are expressed strongly in glial cells, where
      they play a role in brain water balance, neuroexcitation, and glial cell
      migration. Here, we investigated a proposed new role of AQP4 in facilitating cell
      cell adhesion. Measurements were made in differentiated primary glial cell
      cultures from wild-type versus AQP4 knockout mice as well as in null versus AQP4
      transfected L-cells, a cell type lacking endogenous adhesion molecules, and in
      null versus AQP4-transfected Chinese hamster ovary (CHO)-K1 cells and Fisher rat
      thyroid cells. Using established assays of cell-cell adhesion, we found no
      significant effect of AQP4 expression on adhesion in each of the cell types. As a
      positive control, transfection with E-cadherin greatly increased cell-cell
      adhesion. High-level AQP4 expression also did not affect aggregation of plasma
      membrane vesicles in a sensitive quasi-elastic light-scattering assay. Further,
      we found no specific AQP4 binding of a fluorescently labeled oligopeptide
      containing the putative adhesion sequence in the second extracellular loop of
      AQP4. These data provide evidence against involvement of AQP4 in cell-cell
      adhesion.

PMID- 18708070
TI  - Identification of protein interaction partners and protein-protein interaction
      sites.
AB  - Rigid-body docking has become quite successful in predicting the correct
      conformations of binary protein complexes, at least when the constituent proteins
      do not undergo large conformational changes upon binding. However, determining
      whether two given proteins interact is a more difficult problem. Successful
      docking procedures often give equally good scores for proteins that do not
      interact experimentally. This is the case for the multiple minimization approach
      we use here. An analysis of the results where all proteins within a set are
      docked with all other proteins (complete cross-docking) shows that the
      predictions can be greatly improved if the location of the correct binding
      interface on each protein is known, since the experimental complexes are much
      more likely to bring these two interfaces into contact, at the same time as
      yielding good interaction energy scores. While various methods exist for
      identifying binding interfaces, it is shown that simply studying the interaction
      of all potential protein pairs within a data set can itself help to identify the
      correct interfaces.

PMID- 18708069
TI  - Crystal structures of the pro-inflammatory cytokine interleukin-23 and its
      complex with a high-affinity neutralizing antibody.
AB  - Interleukin (IL)-23 is a pro-inflammatory cytokine playing a key role in the
      pathogenesis of several autoimmune and inflammatory diseases. We have determined
      the crystal structures of the heterodimeric p19-p40 IL-23 and its complex with
      the Fab (antigen-binding fragment) of a neutralizing antibody at 2.9 and 1.9 A,
      respectively. The IL-23 structure closely resembles that of IL-12. They share the
      common p40 subunit, and IL-23 p19 overlaps well with IL-12 p35. Along the
      hydrophilic heterodimeric interface, fewer charged residues are involved for IL
      23 compared with IL-12. The binding site of the Fab is located exclusively on the
      p19 subunit, and comparison with published cytokine-receptor structures suggests
      that it overlaps with the IL-23 receptor binding site.

PMID- 18708071
TI  - Kap95p binding induces the switch loops of RanGDP to adopt the GTP-bound
      conformation: implications for nuclear import complex assembly dynamics.
AB  - The asymmetric distribution of the nucleotide-bound state of Ran across the
      nuclear envelope is crucial for determining the directionality of nuclear
      transport. In the nucleus, Ran is primarily in the guanosine 5'-triphosphate
      (GTP)-bound state, whereas in the cytoplasm, Ran is primarily guanosine 5'
      diphosphate (GDP)-bound. Conformational changes within the Ran switch I and
      switch II loops are thought to modulate its affinity for importin-beta. Here, we
      show that RanGDP and importin-beta form a stable complex with a micromolar
      dissociation constant. This complex can be dissociated by importin-beta binding
      partners such as importin-alpha. Surprisingly, the crystal structure of the
      Kap95p-RanGDP complex shows that Kap95p induces the switch I and II regions of
      RanGDP to adopt a conformation that resembles that of the GTP-bound form. The
      structure of the complex provides insights into the structural basis for the
      gradation of affinities regulating nuclear protein transport.

PMID- 18708072
TI  - A simple reaction kinetic model of rapid (G protein dependent) and slow (beta
      Arrestin dependent) transmission.
AB  - In this paper the qualitative dynamic behavior of reaction kinetic models of G
      protein signaling is examined. A simplified basic G protein signaling structure
      is defined, which is extended to be able to take the effect of slow transmission,
      RGS mediated feedback regulation and ERK-phosphatase mediated feedback regulation
      into account. The resulting model gives rise to an acceptable qualitative
      approximation of the G protein dependent and independent ERK activation dynamics
      that is in good agreement with the experimentally observed behavior.

PMID- 18708073
TI  - Airway smooth muscle relaxation induced by 5-HT(2A) receptors: role of Na(+)/K(+)
      ATPase pump and Ca(2+)-activated K(+) channels.
AB  - AIMS: Although 5-hydroxytryptamine (5-HT) contracts airway smooth muscle in many
      mammalian species, in guinea pig and human airways 5-HT causes a contraction
      followed by relaxation. This study explored potential mechanisms involved in the
      relaxation induced by 5-HT. MAIN METHODS: Using organ baths, patch clamp, and
      intracellular Ca(2+) measurement techniques, the effect of 5-HT on guinea pig
      airway smooth muscle was studied. KEY FINDINGS: A wide range of 5-HT
      concentrations caused a biphasic response of tracheal rings. Response to 32
      microM 5-HT was notably reduced by either tropisetron or methiothepin, and almost
      abolished by their combination. Incubation with 10 nM ketanserin significantly
      prevented the relaxing phase. Likewise, incubation with 100 nM charybdotoxin or
      320 nM iberiotoxin and at less extent with 10 microM ouabain caused a significant
      reduction of the relaxing phase induced by 5-HT. Propranolol, L-NAME and 5
      HT(1A), 5-HT(1B)/5-HT(1D) and 5-HT(2B) receptors antagonist did not modify this
      relaxation. Tracheas from sensitized animals displayed reduced relaxation as
      compared with controls. In tracheas precontracted with histamine, a concentration
      response curve to 5-HT (32, 100 and 320 microM) induced relaxation and this
      effect was abolished by charybdotoxin, iberiotoxin or ketanserin. In single
      myocytes, 5-HT in the presence of 3 mM 4-AP notably increased the K(+) currents
      (I(K(Ca))), and they were completely abolished by charybdotoxin, iberiotoxin or
      ketanserin. SIGNIFICANCE: During the relaxation induced by 5-HT two major
      mechanisms seem to be involved: stimulation of the Na(+)/K(+)-ATPase pump, and
      increasing activity of the high-conductance Ca(2+)-activated K(+) channels,
      probably via 5-HT(2A) receptors.

PMID- 18708074
TI  - Alveolar macrophage inducible nitric oxide synthase-dependent pulmonary
      microvascular endothelial cell septic barrier dysfunction.
AB  - Inducible nitric oxide (NO) synthase (iNOS) from neutrophils and alveolar
      macrophages (AM) contributes to the pathophysiology of murine septic acute lung
      injury (ALI). It is not known if AM iNOS has a direct effect on septic pulmonary
      microvascular endothelial cell (PMVEC) permeability. We hypothesized that AM iNOS
      mediates PMVEC permeability in vitro under septic conditions through NO and
      peroxynitrite. 100,000 confluent PMVEC on cell-culture inserts were co-incubated
      with iNOS+/+ vs. iNOS-/- AM, in various ratios of AM to PMVEC. PMVEC injury was
      assessed by trans-PMVEC Evans Blue-labelled albumin flux in the presence or
      absence of cytomix (equimolar TNF-alpha, IL-1beta and IFN-gamma). Cytomix
      stimulation dose-dependently increased trans-PMVEC EB-albumin flux, which was
      exaggerated (1.4+/-0.1% vs. 0.4+/-0.1% in unstimulated PMVEC, p<0.05) in the
      presence of iNOS+/+, but not iNOS-/-, AM in the upper compartment. Similarly,
      iNOS+/+, but not iNOS-/-, AM in the lower compartment also enhanced septic trans
      PMVEC albumin leak. The mechanism of iNOS-dependent septic PMVEC permeability was
      pursued through pharmacologic studies with inhibitors of NOS, and scavengers of
      NO, superoxide, and peroxynitrite, and treatment of PMVEC with the NO donor, DETA
      NONOate. Septic iNOS+/+ AM-dependent trans-PMVEC albumin leak was significantly
      attenuated by pharmacologic iNOS inhibition (L-NAME and 1400W), and scavenging of
      either NO (oxyhemoglobin), superoxide (PEG-SOD), or peroxynitrite (FeTPPS).
      Exogenous NO (DETA-NONOate) had no effect on PMVEC permeability. These data are
      consistent with a direct role of AM iNOS in septic PMVEC barrier dysfunction,
      which is likely mediated, in part, through peroxynitrite.

PMID- 18708075
TI  - Visualizing loss of heterozygosity in living mouse cells and tissues.
AB  - Loss of heterozygosity (LOH) in somatic cells can contribute to the genesis of
      cancer, but little is known about the frequency with which LOH occurs in normal
      cells of the body. To detect LOH in situ, we studied mouse shYFP embryonic stem
      (ES) cells and cells of the intestinal epithelia derived from these ES cells.
      shYFP ES cells are heterozygous at the ROSA26 locus. One copy of the locus
      carries a gene encoding a yellow fluorescent protein (YFP), while the other copy
      harbors an shRNA gene that produces a short hairpin RNA (shRNA) molecule that
      causes degradation of YFP mRNA. Nearly all cells in shYFP populations were
      faintly fluorescent, but brightly fluorescent cells arose at a rate of
      approximately 10(-5)bright cells/generation. Bright cells lacked the gene
      encoding the shRNA and contained two copies of the YFP gene. Comparison of these
      results to previous data on LOH in ES cells that lacked interfering shRNA showed
      that LOH in shYFP cells was not influenced by the presence of the shRNA. Bright
      cells were also seen in intestinal villi of chimeric mice made by injecting
      blastocysts with shYFP cells. These data demonstrate that this approach can
      detect LOH and suggest that it will allow detection of LOH in a broad array of
      tissues and cell types in transgenic mice made from shYFP cells.

PMID- 18708076
TI  - Sustained administration of bupropion alters the neuronal activity of serotonin,
      norepinephrine but not dopamine neurons in the rat brain.
AB  - Bupropion is widely used in the treatment of depression. There are, however,
      limited data on its long-term effects on monoaminergic neurons and therefore the
      mechanism of its delayed onset of action is at present not well understood. The
      present study was conducted to examine the effects of prolonged bupropion
      administration on the firing activity of dorsal raphe nucleus (DRN), locus
      coeruleus (LC), and ventral tegmental area (VTA) neurons. Spontaneously firing
      neurons were recorded extracellularly in rats anesthetized with chloral hydrate.
      Bupropion (30 mg/kg/day) was administered using subcutaneously implanted
      minipumps. In the DRN, the firing rate of serotonin (5-HT) neurons was
      significantly increased after 2, 7 and 14 days of administration. The suppressant
      effect of LSD was significantly diminished after the two-day regimen, indicating
      a desensitization of 5-HT1A autoreceptors. In the LC, the firing rate of
      norepinephrine (NE) neurons was significantly attenuated after a 2-day regimen,
      but recovered progressively over 14 days of administration. The suppressant
      effect of clonidine on NE neuronal firing was significantly attenuated in rats
      treated with bupropion for 14 days, indicating a desensitization of alpha2
      adrenoceptors. In the VTA, neither 2 nor 14 days of bupropion administration
      altered the firing and burst activity of dopamine neurons. These results indicate
      that bupropion, unlike 5-HT reuptake inhibitors, promptly increased 5-HT neuronal
      activity, due to early desensitization of the 5-HT1A autoreceptor. The gradual
      recovery of neuronal firing of NE neurons, due to the desensitization of alpha2
      adrenoceptors, in the presence of the sustained increase in 5-HT neuronal firing,
      may explain in part the delayed onset of action of bupropion in major depression.

PMID- 18708078
TI  - An antidepressant behaviour in mice carrying a gene-specific InsP3R1, InsP3R2 and
      InsP3R3 protein knockdown.
AB  - Evidence has accumulated for the involvement of Ca(2+) in the pathophysiology of
      mood disorders. Elevations in both resting and stimulated intracellular Ca(2+)
      levels in patients with affective disorders have been reported. The role of
      inositol-1,4,5-trisphosphate receptors (InsP3Rs), which allow mobilization of
      intracellular Ca(2+) stores, was, then, investigated in the mouse forced swimming
      test. InsP3R antagonists (heparin, xestospongin C) as well as an inositol
      monophosphatase inhibitor (LiCl) showed an antidepressant activity of intensity
      comparable to clinically used antidepressants. InsP3Rl, InsP3R2 and InsP3R3
      knockdown mice were obtained to investigate the role of InsP3R isoforms. We
      generated mice carrying a cerebral knockdown of InsP3Rl, InsP3R2 and InsP3R3
      proteins by administering antisense oligonucleotides complementary to the
      sequence of InsP3Rl, InsP3R2 and InsP3R3. These antisense-treated mice showed a
      specific InsP3R protein level reduction in the mouse cerebral cortex and
      hippocampus, demonstrated by immunoblotting, immunoprecipitation and
      immunocytochemistry experiments. Knockdown mice for each InsP3R isoforms showed
      an antidepressant behaviour and the induced phenotype was reversible disappearing
      7 days after the end of the treatment. The absence of impairment of locomotor
      activity and spontaneous mobility in InsP3R knockdown mice was revealed. These
      results indicate the involvement of the InsP3R-mediated pathway in the modulation
      of depressive conditions and may be useful for the development of new
      therapeutical strategies for the treatment of mood disorders.

PMID- 18708077
TI  - Targeting extinction and reconsolidation mechanisms to combat the impact of drug
      cues on addiction.
AB  - Drug addiction is a progressive and compulsive disorder, where recurrent craving
      and relapse to drug-seeking occur even after long periods of abstinence. A major
      contributing factor to relapse is drug-associated cues. Here we review behavioral
      and pharmacological studies outlining novel methods of effective and persistent
      reductions in cue-induced relapse behavior in animal models. We focus on
      extinction and reconsolidation of cue-drug associations as the memory processes
      that are the most likely targets for interventions. Extinction involves the
      formation of new inhibitory memories rather than memory erasure; thus, it should
      be possible to facilitate the extinction of cue-drug memories to reduce relapse.
      We propose that context-dependency of extinction might be altered by mnemonic
      agents, thereby enhancing the efficacy of cue-exposure therapy as treatment
      strategy. In contrast, interfering with memory reconsolidation processes can
      disrupt the integrity or strength of specific cue-drug memories. Reconsolidation
      is argued to be a distinct process that occurs over a brief time period after
      memory is reactivated/retrieved - when the memory becomes labile and vulnerable
      to disruption. Reconsolidation is thought to be an independent, perhaps opposing,
      process to extinction and disruption of reconsolidation has recently been shown
      to directly affect subsequent cue-drug memory retrieval in an animal model of
      relapse. We hypothesize that a combined approach aimed at both enhancing the
      consolidation of cue-drug extinction and interfering with the reconsolidation of
      cue-drug memories will have a greater potential for persistently inhibiting cue
      induced relapse than either treatment alone.

PMID- 18708079
TI  - Antipsychotic-induced alterations in CB1 receptor-mediated G-protein signaling
      and in vivo pharmacology in rats.
AB  - Dysregulation of the endocannabinoid and dopamine systems has been implicated in
      schizophrenia. The purpose of this study was to examine the effects of sub
      chronic treatment with two antipsychotics on CB1 receptor-mediated in vitro and
      in vivo effects. Adult and adolescent male and female rats were injected twice
      daily with haloperidol (0.3 mg/kg), clozapine (10 mg/kg), or saline for 10 days.
      Subsequently, CB1 receptor number and function were assessed by [3H]SR141716 and
      WIN55,212-2-stimulated [35S]GTPgammaS binding, respectively. The effects of sub
      chronic antipsychotic treatment on the in vivo actions of Delta9
      tetrahydrocannabinol (Delta9-THC) were also evaluated. In adult female rats,
      antipsychotic treatment attenuated maximal stimulation of CB1 receptor-mediated G
      protein activity in the striatum (clozapine) and prefrontal cortex (both
      antipsychotics), but not in the ventral midbrain. Associated changes in CB1
      receptor number were not observed, suggesting that this attenuation was not due
      to downregulation. In vivo, sub-chronic treatment with clozapine, but not
      haloperidol, attenuated Delta9-THC-induced suppression of activity in adult
      females, whereas neither drug altered hypothermia or catalepsy. In contrast,
      antipsychotic treatment did not change CB1 receptor-mediated G-protein activation
      in any brain region in adult male rats and in adolescents of either sex. In vivo,
      haloperidol, but not clozapine, enhanced Delta9-THC-mediated suppression of
      activity and hypothermia in adult male rats whereas neither antipsychotic
      affected Delta9-THC-induced in vivo effects in adolescent rats. These findings
      suggest that modulation of the endocannabinoid system might contribute in a sex-
      and age-selective manner to differences in motor side effects of clozapine versus
      haloperidol.

PMID- 18708080
TI  - Cortico-subcortical organization of language networks in the right hemisphere: an
      electrostimulation study in left-handers.
AB  - We have studied the configuration of the cortico-subcortical language networks
      within the right hemisphere (RH) in nine left-handers, being operated on while
      awake for a cerebral glioma. Intraoperatively, language was mapped using cortico
      subcortical electrostimulation, to avoid permanent deficit. In frontal regions,
      cortical stimulation elicited articulatory disorders (ventral premotor cortex),
      anomia (dorsal premotor cortex), speech arrest (pars opercularis), and semantic
      paraphasia (dorsolateral prefrontal cortex). Insular stimulation generated
      dysarthria, parietal stimulation phonemic paraphasias, and temporal stimulation
      semantic paraphasias. Subcortically, the superior longitudinal fasciculus
      (inducing phonological disturbances when stimulated), inferior occipito-frontal
      fasciculus (eliciting semantic disturbances during stimulation), subcallosal
      fasciculus (generating control disturbances when stimulated), and common final
      pathway (inducing articulatory disorders during stimulation) were identified.
      These cortical and subcortical structures were preserved, avoiding permanent
      aphasia, despite a transient immediate postoperative language worsening. Both
      intraoperative results and postsurgical transitory dysphasia support the major
      role of the RH in language in left-handers, and provide new insights into the
      anatomo-functional cortico-subcortical organization of the language networks in
      the RH-suggesting a "mirror" configuration in comparison to the left hemisphere.

PMID- 18708081
TI  - The crucial protective role of glutathione against tienilic acid hepatotoxicity
      in rats.
AB  - To investigate the hepatotoxic potential of tienilic acid in vivo, we
      administered a single oral dose of tienilic acid to Sprague-Dawley rats and
      performed general clinicopathological examinations and hepatic gene expression
      analysis using Affymetrix microarrays. No change in the serum transaminases was
      noted at up to 1000 mg/kg, although slight elevation of the serum bile acid and
      bilirubin, and very mild hepatotoxic changes in morphology were observed. In
      contrast to the marginal clinicopathological changes, marked upregulation of the
      genes involved in glutathione biosynthesis [glutathione synthetase and glutamate
      cysteine ligase (Gcl)], oxidative stress response [heme oxygenase-1 and NAD(P)H
      dehydrogenase quinone 1] and phase II drug metabolism (glutathione S-transferase
      and UDP glycosyltransferase 1A6) were noted after 3 or 6 h post-dosing. The
      hepatic reduced glutathione level decreased at 3-6 h, and then increased at 24 or
      48 h, indicating that the upregulation of NF-E2-related factor 2 (Nrf2)-regulated
      gene and the late increase in hepatic glutathione are protective responses
      against the oxidative and/or electrophilic stresses caused by tienilic acid. In a
      subsequent experiment, tienilic acid in combination with l-buthionine-(S,R)
      sulfoximine (BSO), an inhibitor of Gcl caused marked elevation of serum alanine
      aminotransferase (ALT) with extensive centrilobular hepatocyte necrosis, whereas
      BSO alone showed no hepatotoxicity. The elevation of ALT by this combination was
      observed at the same dose levels of tienilic acid as the upregulation of the Nrf2
      regulated genes by tienilic acid alone. In conclusion, these results suggest that
      the impairment of glutathione biosynthesis may play a critical role in the
      development of tienilic acid hepatotoxicity through extensive oxidative and/or
      electrophilic stresses.

PMID- 18708082
TI  - Involvement of MAPKs, NF-kappaB and p300 co-activator in IL-1beta-induced
      cytosolic phospholipase A2 expression in canine tracheal smooth muscle cells.
AB  - Cytosolic phospholipase A2 (cPLA2) plays a pivotal role in mediating agonist
      induced arachidonic acid release for prostaglandin (PG) synthesis during
      stimulation with interleukin-1beta (IL-1beta). However, the mechanisms underlying
      IL-1beta-induced cPLA2 expression and PGE2 synthesis by canine tracheal smooth
      muscle cells (CTSMCs) have not been defined. IL-1beta induced cPLA2 protein and
      mRNA expression, PGE2 production, and phosphorylation of p42/p44 MAPK, p38 MAPK
      (ATF2), and JNK (c-Jun) in a time- and concentration-dependent manner, determined
      by Western blotting, RT-PCR, and ELISA, which was attenuated by the inhibitors of
      MEK1/2 (U0126), p38 MAPK (SB202190), and JNK (SP600125), or transfection with
      dominant negative mutants of MEK1/2, p38, and JNK, respectively. Furthermore, IL
      1beta-induced cPLA2 expression and PGE2 synthesis was inhibited by a selective NF
      kappaB inhibitor (helenalin) or transfection with dominant negative mutants of NF
      kappaB inducing kinase (NIK), IkappaB kinase (IKK)-alpha, and IKK-beta.
      Consistently, IL-1beta stimulated both IkappaB-alpha degradation and NF-kappaB
      translocation into nucleus in these cells. NF-kappaB translocation was blocked by
      helenalin, but not by U0126, SB202190, and SP600125. MAPKs together with NF
      kappaB-activated p300 recruited to cPLA2 promoter thus facilitating the binding
      of NF-kappaB to cPLA2 promoter region and expression of cPLA2 mRNA. IL-1beta
      induced cPLA2 expression and PGE2 production was inhibited by actinomycin D and
      cycloheximide, indicating the involvement of transcriptional and translational
      events in these responses. These results suggest that in CTSMCs, IL-1beta-induced
      cPLA2 expression and PGE2 synthesis was independently mediated through activation
      of MAPKs and NF-kappaB pathways and was connected to p300 recruitment and
      activation.

PMID- 18708083
TI  - The impact of different nanoparticle surface chemistry and size on uptake and
      toxicity in a murine macrophage cell line.
AB  - This study investigated the uptake, kinetics and cellular distribution of
      different surface coated quantum dots (QDs) before relating this to their
      toxicity. J774.A1 cells were treated with organic, COOH and NH2 (PEG) surface
      coated QDs (40 nM). Model 20 nm and 200 nm COOH-modified coated polystyrene beads
      (PBs) were also examined (50 microg ml(-1)). The potential for uptake of QDs was
      examined by both fixed and live cell confocal microscopy as well as by flow
      cytometry over 2 h. Both the COOH 20 nm and 200 nm PBs were clearly and rapidly
      taken up by the J774.A1 cells, with uptake of 20 nm PBs being relatively quicker
      and more extensive. Similarly, COOH QDs were clearly taken up by the macrophages.
      Uptake of NH2 (PEG) QDs was not detectable by live cell imaging however, was
      observed following 3D reconstruction of fixed cells, as well as by flow
      cytometry. Cells treated with organic QDs, monitored by live cell imaging, showed
      only a small amount of uptake in a relatively small number of cells. This uptake
      was insufficient to be detected by flow cytometry. Imaging of fixed cells was not
      possible due to a loss in cell integrity related to cytotoxicity. A significant
      reduction (p<0.05) in the fluorescent intensity in a cell-free environment was
      found with organic QDs, NH2 (PEG) QDs, 20 nm and 200 nm PBs at pH 4.0 (indicative
      of an endosome) after 2 h, suggesting reduced stability. No evidence of
      exocytosis was found over 2 h. These findings confirm that surface coating has a
      significant influence on the mode of NP interaction with cells, as well as the
      subsequent consequences of that interaction.

PMID- 18708084
TI  - Organochlorines inhibit acetaminophen glucuronidation by redirecting UDP
      glucuronic acid towards the D-glucuronate pathway.
AB  - Industry-derived organochlorines are persistent environmental pollutants that are
      a continuing health concern. The effects of these compounds on drug metabolism
      are not well understood. In the current study we present evidence that the
      inhibition of acetaminophen (APAP) glucuronidation by minute concentrations of
      organochlorines correlates well with their ability to stimulate the d-glucuronate
      pathway leading to ascorbate synthesis. A set of 6 arylated organochlorines,
      including 5 PCB (polychlorinated biphenyl) congeners, were assessed for their
      effects on APAP glucuronidation in isolated hepatocytes from male Sprague-Dawley
      rats. The capacity of each organochlorine to inhibit APAP glucuronidation was
      found to be directly proportional to its capacity to stimulate ascorbate
      synthesis. PCB153, PCB28 and bis-(4-chlorophenyl sulfone) (BCPS) in increasing
      order were the most effective organochlorines for inhibiting APAP glucuronidation
      and stimulating the d-glucuronate pathway. None of the 3 inhibitors of APAP
      glucuronidation were able to alter the expression of UGT1A6, UGT1A7 and UGT1A8
      (the major isoforms responsible for APAP glucuronidation in the rat), however,
      their efficacy at inhibiting APAP glucuronidation was proportional to their
      capacity to deplete UDP-glucuronic acid (UDPGA). BCPS-mediated inhibition of APAP
      glucuronidation in isolated hepatocytes had non-competitive characteristics and
      was insensitive to the inactivation of cytochrome P450. The effective
      organochlorines were also able to selectively stimulate the hydrolysis of UDPGA
      to UDP and glucuronate in isolated microsomes, but could not inhibit APAP
      glucuronidation in microsomes when UDPGA was in excess. We conclude that
      organochlorines are able to inhibit APAP glucuronidation in hepatocytes by
      depleting UDPGA via redirecting UDPGA towards the d-glucuronate pathway. Because
      the inhibition is non-competitive, low concentrations of these compounds could
      have long term inhibitory effects on the glucuronidating capacity of hepatocytes.

PMID- 18708085
TI  - Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor.
AB  - Gonadotropin-releasing hormone (GnRH) is the first key hormone of reproduction.
      GnRH analogs are extensively used in in vitro fertilization, and treatment of sex
      hormone-dependent cancers, due to their ability to bring about 'chemical
      castration'. The interaction of GnRH with its cognate type I receptor (GnRHR) in
      pituitary gonadotropes results in the activation of Gq/G(11), phospholipase Cbeta
      (PLCbetaI), PLA(2), and PLD. Sequential activation of the phospholipases
      generates the second messengers inositol 1, 4, 5-trisphosphate (IP(3)),
      diacylglycerol (DAG), and arachidonic acid (AA), which are required for Ca(2+)
      mobilization, the activation of various protein kinase C isoforms (PKCs), and the
      production of prostaglandin (PG) and other metabolites of AA, respectively. PKC
      isoforms are the major mediators of the downstream activation of a number of
      mitogen-activated protein kinase (MAPK) cascades by GnRH, namely: extracellular
      signal-regulated kinase (ERK), jun-N-terminal kinase (JNK), and p38MAPK. The
      activated MAPKs phosphorylate both cytosolic and nuclear proteins to initiate the
      transcriptional activation of the gonadotropin subunit genes and the GnRHR. While
      Ca(2+) mobilization has been found to initiate rapid gonadotropin secretion,
      Ca(2+), together with various PKC isoforms, MAPKs and AA metabolites also serve
      as key nodes, in the GnRH-stimulated signaling network that enables the
      gonadotropes to decode GnRH pulse frequencies and translating that into
      differential gonadotropin synthesis and release. Even though pulsatility of GnRH
      is recognized as a major determinant for differential gonadotropin subunit gene
      expression and gonadotropin secretion very little is yet known about the
      signaling circuits governing GnRH action at the 'Systems Biology' level. Direct
      apoptotic and metastatic effects of GnRH analogs in gonadal steroid-dependent
      cancers expressing the GnRHR also seem to be mediated by the activation of the
      PKC/MAPK pathways. However, the mechanisms dictating life (pituitary) vs. death
      (cancer) decisions made by the same GnRHR remain elusive. Understanding these
      molecular mechanisms triggered by the GnRHR through biochemical and 'Systems
      Biology' approaches would provide the basis for the construction of the dynamic
      connectivity maps, which operate in the various cell types (endocrine, cancer,
      and immune system) targeted by GnRH. The connectivity maps will open a new vista
      for exploring the direct effects of GnRH analogs in tumors and the design of
      novel combined therapies for fertility control, reproductive disorders and
      cancers.

PMID- 18708086
TI  - A review of mediators of behavior in interventions to promote physical activity
      among children and adolescents.
AB  - BACKGROUND: The effectiveness of interventions to promote physical activity in
      youths is still developing. To develop a better understanding "what works",
      researchers are now focusing on constructing an evidence base for mediators of
      behavior change. METHODS: We reviewed studies that examined the direct effect of
      physical activity interventions on hypothesized mediators and the relationship
      between mediators and physical activity in young people (aged 5 to 18 years).
      Studies were identified via electronic database searches and scanning references
      against predetermined quality criteria. RESULTS: We found seven studies that
      evaluated three mediator groups: cognitive, behavioral and interpersonal
      mediators. Self-efficacy was the most commonly assessed mediator in youth
      interventions and there was strong support for its role in mediating the relation
      between theory-based interventions and physical activity. There was some support
      for the importance of behavioral strategies as mediators of behavior, but no
      support for the mediating influence of interpersonal factors. CONCLUSIONS:
      Despite recognition of the importance of mediation studies, few interventions
      have assessed mediators of physical activity behavior in youth interventions. The
      small number of studies examining mediators of behavior and the variability in
      study design and quality prevent us from forming strong conclusions regarding the
      most effective mediators of behavior.

PMID- 18708087
TI  - Alcohol consumption behavior of pregnant women in Japan.
AB  - OBJECTIVE: This study was conducted to clarify the prevalence of alcohol
      consumption among pregnant women in Japan and its associated factors. METHOD: 344
      institutions participated in the survey which was conducted in February 2006.
      Each subject was requested to fill out a self-administered anonymous
      questionnaire. Factors associated with alcohol consumption during pregnancy were
      examined using the chi-squared test and logistic regression analysis. RESULTS:
      The number of effective responses was 18,965. The prevalence of alcohol
      consumption before the confirmation of pregnancy and during pregnancy was 44.6%
      and 4.6% respectively. The following items were recognized as being associated
      with promoting alcohol consumption during pregnancy: greater number of weeks of
      pregnancy, more pregnancies, fewer years of schooling, being employed, an alcohol
      consumption before the confirmation of pregnancy, smoking during pregnancy,
      ignorance about the effects of alcohol consumption on fetuses, receiving advice
      regarding alcohol abstention, difficulty maintaining sleep, and daytime
      sleepiness. CONCLUSION: It is important to have a more comprehensive
      understanding of the factors associated with the alcohol consumption behavior of
      pregnant women, as revealed in the present study, in order to develop future
      policies for preventing alcohol consumption among pregnant women.

PMID- 18708088
TI  - Characterization of folate-graft-chitosan as a scaffold for nitric oxide release.
AB  - The preparation and characterization of nitric oxide (NO)-releasing chitosan
      folate conjugates were reported. The secondary amine chitosan-folate conjugates
      exhibited a high storage capacity for NO (up to 84.3 nmol NO/mg) (when the graft
      rate of folate was 12.5%), greatly increasing the "payload" of released NO with
      the graft rate of folate increasing. The NO release durations (12h) observed for
      secondary amine the chitosan-folate conjugates with the high graft rate (12.5%)
      were largerly shorter compared to O2-protected diazeniumliolates with BrCH2CH3
      (24 h), thus illustrating a macromolecular effect on NO release kinetics.

PMID- 18708089
TI  - Biobehavior of the human love of salt.
AB  - We are beginning to understand why humans ingest so much salt. Here we address
      three issues: The first is whether our salt appetite is similar to that in
      animals, which we understand well. Our analysis suggests that this is doubtful,
      because of important differences between human and animal love of salt. The
      second issue then becomes how our predilection for salt is determined, for which
      we have a partial description, resting on development, conditioning, habit, and
      dietary culture. The last issue is the source of individual variation in salt
      avidity. We have partial answers to that too in the effects of perinatal sodium
      loss, sodium loss teaching us to seek salt, and gender. Other possibilities are
      suggested. From animal sodium appetite we humans may retain the lifelong
      enhancement of salt intake due to perinatal sodium loss, and a predisposition to
      learn the benefits of salt when in dire need. Nevertheless, human salt intake
      does not fit the biological model of a regulated sodium appetite. Indeed this
      archetypal 'wisdom of the body' fails us in all that has to do with behavioral
      regulation of this most basic need.

PMID- 18708090
TI  - Beta1 integrin in tissue remodelling and repair: from phenomena to concepts.
AB  - There is substantial molecular evidence for the involvement of beta1 integrin in
      tissue organisation and remodelling, which confers a key role in cell growth,
      differentiation, migration, and survival. This role has been, in part,
      highlighted using the transgenic approach which does little to define the more
      subtle functions such as those controlled by avidity regulation. Upon activation
      integrins in general, including beta1 integrin, are known to exhibit global
      structural rearrangement and exposure of ligand binding sites. Recent evidence
      has revealed a role of beta1 integrin modulation in tissue repair and
      regeneration. The anomalies and phenomena describing the roles of beta1 integrin
      in tissue remodelling are reviewed, as well as the tools which have been used to
      define the functions of beta1 integrin and its impact on our understanding of the
      diverse roles of beta1 integrin in remodelling. This eclectic mix of phenomena is
      conceptualised to form a unified hypothesis of a novel understanding of both
      tissue injury and repair.

PMID- 18708091
TI  - The cardiac sarcolemmal ATP-sensitive potassium channel as a novel target for
      anti-arrhythmic therapy.
AB  - The activation of cardiac cell membrane ATP-sensitive potassium channels during
      myocardial ischemia promotes potassium efflux, reductions in action potential
      duration, and heterogeneities in repolarization, thereby creating a substrate for
      re-entrant arrhythmias. Drugs that block this channel should be particularly
      effective anti-arrhythmic agents. Indeed, non-selective ATP-sensitive potassium
      channel antagonists, (e.g., glibenclamide) can prevent arrhythmias associated
      with myocardial ischemia. However, these non-selective antagonists have important
      non-cardiac actions that promote insulin release and hypoglycemia (pancreatic
      beta-cells), reduce coronary blood flow (vascular smooth muscle cells), prevent
      ischemia preconditioning (cardiac mitochondrial channels) and depress cardiac
      contractile function. The ATP-sensitive potassium channel consists of a pore
      forming inward rectifying potassium channel (Kir6.1 or Kir6.2) and a regulatory
      subunit (sulfonylurea receptors, SUR1, SUR2A &SUR2B). The Kir6.2/SUR2A
      combination appears to be preferentially expressed on cardiac cell membranes. As
      such, it should be possible to develop agents selective for cardiac sarcolemmal
      ATP-sensitive potassium channels. The novel compounds HMR 1883 (or its sodium
      salt HMR 1098) or HMR 1402 have been shown to block selectively the cardiac
      sarcolemmal ATP-sensitive potassium channels. These drugs attenuated ischemically
      induced changes in cardiac electrical properties and prevented malignant
      arrhythmias without the untoward effects of other drugs. Since the ATP-sensitive
      potassium channel only becomes active as ATP levels fall, these drugs have the
      added advantage that they would have effects only on ischemic tissue with little
      or no effect noted on normal tissue. Thus, selective antagonists of the cardiac
      cell surface ATP-sensitive potassium channel may represent a new class of
      ischemia selective anti-arrhythmic medications.

PMID- 18708092
TI  - New insights into brain BDNF function in normal aging and Alzheimer disease.
AB  - The decline observed during aging involves multiple factors that influence
      several systems. It is the case for learning and memory processes which are
      severely reduced with aging. It is admitted that these cognitive effects result
      from impaired neuronal plasticity, which is altered in normal aging but mainly in
      Alzheimer disease. Neurotrophins and their receptors, notably BDNF, are expressed
      in brain areas exhibiting a high degree of plasticity (i.e. the hippocampus,
      cerebral cortex) and are considered as genuine molecular mediators of functional
      and morphological synaptic plasticity. Modification of BDNF and/or the expression
      of its receptors (TrkB.FL, TrkB.T1 and TrkB.T2) have been described during normal
      aging and Alzheimer disease. Interestingly, recent findings show that some
      physiologic or pathologic age-associated changes in the central nervous system
      could be offset by administration of exogenous BDNF and/or by stimulating its
      receptor expression. These molecules may thus represent a physiological reserve
      which could determine physiological or pathological aging. These data suggest
      that boosting the expression or activity of these endogenous protective systems
      may be a promising therapeutic alternative to enhance healthy aging.

PMID- 18708093
TI  - Rapid, postmortem 9.4 T MRI of spinal cord injury: correlation with histology and
      survival times.
AB  - High field magnetic resonance imaging (MRI) has been increasingly used to assess
      experimental spinal cord injury (SCI). In the present investigation, after
      partial spinal cord injury and excision of the whole spine, pathological changes
      of the spinal cord were studied in spinal cord-spine blocks, from the acute to
      the chronic state (24 h to 5 months). Using proton density (PD) weighted imaging
      parameters at a magnetic field strength of 9.4 tesla (T), acquisition times
      ranging from <1 to 10 h per specimen were used. High in-plane pixel resolution
      (68 and 38 microm, respectively) was obtained, as well as high signal-to-noise
      ratio (SNR), which is important for optimal contrast settings. The quality of the
      resulting MR images was demonstrated by comparison with histology. The cord and
      the lesion were shown in their anatomical surroundings, detecting cord swelling
      in the acute phase (24 h to 1 week) and cord atrophy at the chronic stage.
      Haemorrhage was detected as hypo-intense signal. Oedema, necrosis and scarring
      were hyper-intense but could not be distinguished. Histology confirmed that the
      anatomical delimitation of the lesion extent by MRI was precise, both with high
      and moderate resolution. The present investigation thus demonstrates the
      precision of spinal cord MRI at different survival delays after compressive
      partial SCI and establishes efficient imaging parameters for postmortem PD MRI.

PMID- 18708094
TI  - An expression system to screen for inhibitors of parasite glucose transporters.
AB  - Chemotherapy of parasitic protists is limited by general toxicity, high expense
      and emergence of resistance to currently available drugs. Thus methods to
      identify new leads for further drug development are increasingly important.
      Previously, glucose transporters have been validated as new drug targets for
      protozoan parasites including Plasmodium falciparum, Leishmania mexicana and
      Trypanosoma brucei. A recently derived glucose transporter null mutant
      (Deltalmgt) of L. mexicana was used to functionally express various heterologous
      glucose transporters including those from T. brucei THT1, P. falciparum PfHT and
      human GLUT1-resulting in recovery of growth of the Deltalmgt null mutant in
      glucose replete medium. This heterologous expression system can be employed to
      screen for compounds that retard growth by inhibiting the expressed glucose
      transporter. The ability of this expression system to identify specific glucose
      transporter inhibitors was demonstrated using 3-O-undec-10-enyl-d-glucose, a
      previously described specific inhibitor of PfHT.

PMID- 18708095
TI  - Triiodothyronine (T3) stimulates food intake via enhanced hypothalamic AMP
      activated kinase activity.
AB  - Thyroid hormone regulates food intake. We previously reported that rats with
      triiodothyronine (T3)-induced thyrotoxicosis display hyperphagia associated with
      suppressed circulating leptin levels, increased hypothalamic neuropeptide Y (NPY)
      mRNA and decreased hypothalamic pro-opiomelanocortin (POMC) mRNA. AMP-activated
      kinase (AMPK) is a serine/threonine protein kinase that is activated when
      cellular energy is depleted. We hypothesized that T3 causes an increase in
      hypothalamic AMPK activity, which in turn contributes to the development of T3
      induced hyperphagia. Rats that were given s.c. injections of T3 (4.5 nmol/kg) had
      increased food intake 2 h later without alterations in NPY and POMC mRNA levels,
      but with increased hypothalamic phosphorylated AMPK (169%) and phosphorylated
      acetyl-CoA carboxylase (194%). To determine the more chronic effects of T3, rats
      were given 6 daily s.c. injection of T3 or the vehicle. Food intake was
      significantly increased. Multiple T3 injections increased hypothalamic
      phosphorylated AMPK (278%) and phosphorylated acetyl-CoA carboxylase (335%)
      compared to the controls. Intracerebroventricular administration of compound C,
      an AMPK inhibitor, blocked the food intake induced by a single or multiple
      injections of T3. Taken together, these results suggest that enhanced
      hypothalamic AMPK phosphorylation contributes to T3-induced hyperphagia.
      Hypothalamic AMPK plays an important role in the regulation of food intake and
      body weight.

PMID- 18708096
TI  - Western blot can distinguish natural and acquired antibodies to Mycoplasma
      agassizii in the desert tortoise (Gopherus agassizii).
AB  - Mycoplasma agassizi has been identified as a cause of upper respiratory tract
      disease (URTD) in the threatened Mojave population of the desert tortoise
      (Gopherus agassizii), and anti-M. agassizii antibodies have been found by ELISA
      in as many as 15% of these animals across their geographic range. Here we report
      that a cohort of 16 egg-reared desert tortoises never exposed to M. agassizii had
      ELISA antibody titers to this organism that overlapped with titers obtained from
      some M. agassizii-infected tortoises. These natural antibodies were predominantly
      of the IgM class. Western blots of plasma from these non-infected tortoises
      produced a characteristic banding pattern against M. agassizii antigens. A group
      of 38 wild-caught desert tortoises was tested by ELISA, and although some of
      these tortoises had antibody titers significantly higher than the non-infected
      tortoises, there was considerable overlap at the lower titer levels. However,
      Western blot analysis revealed distinct banding patterns that could readily
      distinguish between the non-infected tortoises and tortoises with acquired
      antibodies, regardless of ELISA antibody titers. We conclude that desert
      tortoises have natural antibodies to M. agassizii that can compromise the
      determination of infection status by ELISA. However, the Western blot technique
      can distinguish between natural and acquired antibody patterns and can be used to
      confirm the diagnosis of M. agassizii infections in the desert tortoise.

PMID- 18708097
TI  - Functional whole-colony screening method to identify antimicrobial peptides.
AB  - A high throughput method for screening cDNA libraries has been developed to
      identify putative antimicrobial peptides (AMPs). It is based on a rapid dye
      inclusion assay for assessing antagonism of bacterial viability. Colonies are
      grown on a membrane on a permissive medium until full colony size is reached. The
      membrane, supporting the array of colonies, is transferred onto an inductive
      medium containing a vital dye. Upon expression of any antagonizing peptides, the
      cell membrane becomes compromised allowing dye infusion to permit visual
      identification of deleterious peptides. Our approach was validated by screening a
      synthetic oligonucleotide library expressed in Escherichia coli. A random
      oligonucleotide library, containing inserts of up to 75 nucleotides in length was
      constructed and expressed in E. coli. From a potential pool of 100000 peptides,
      in a single round of screening, three were found to be antimicrobial: L1, L3, and
      L8. Peptide L1 was shown to have a concentration-dependent bactericidal effect
      against Gram-negative E. coli and moderate biostatic activity against the Gram
      positive bacteria Listeria monocytogenes. L8 was found to have bacteriostatic,
      and possibly bactericidal effect against E. coli, Pseudomonas aeruginosa and
      Salmonella typhimurium. These results validated this high throughput AMP
      identification assay based on filter bound colony array libraries and vital dye
      inclusion.

PMID- 18708098
TI  - Probe-based negative selection for underrepresented phylotypes in large
      environmental clone libraries.
AB  - Studies based on cloning and sequencing to investigate microbial diversity in a
      vast range of samples has become widespread in recent years. Results have
      revealed immense microbial diversity in many different environments, but also
      dominance of a few sequence types in the constructed clone libraries. Here we
      describe a method to enrich the clone libraries by avoiding sequencing of known,
      abundant sequence types, instead focusing on novel, rare ones. The protocol is
      based on gridding the PCR products from clone libraries on membranes and
      hybridisation of species-specific probes. Clones that do not give positive
      hybridisation results are sequenced. This method was used for fungal clone
      libraries from compost samples. Altogether 1536 clones were gridded and six
      probes used. From these clones, 59% hybridised with a probe, and therefore, only
      41% of the clones were sequenced. In addition, 384 samples were sequenced to
      verify the hybridisation results. The numbers of false-negative (5.2%) and false
      positive (3.9%) hybridisations were low. This method provides a mean of lowering
      the costs of sequencing projects and speeding up the process of characterising
      microbial diversity in environmental samples. The method is especially suitable
      for samples with a few dominating sequence types.

PMID- 18708099
TI  - Affective valence, stimulus attributes, and P300: color vs. black/white and
      normal vs. scrambled images.
AB  - Pictures from the International Affective Picture System (IAPS) were selected to
      manipulate affective valence (unpleasant, neutral, pleasant) while keeping
      arousal level the same. The pictures were presented in an oddball paradigm, with
      a visual pattern used as the standard stimulus. Subjects pressed a button
      whenever a target was detected. Experiment 1 presented normal pictures in color
      and black/white. Control stimuli were constructed for both the color and
      black/white conditions by randomly rearranging 1 cm square fragments of each
      original picture to produce a "scrambled" image. Experiment 2 presented the same
      normal color pictures with large, medium, and small scrambled condition (2, 1,
      and 0.5 cm squares). The P300 event-related brain potential demonstrated larger
      amplitudes over frontal areas for positive compared to negative or neutral images
      for normal color pictures in both experiments. Attenuated and nonsignificant
      valence effects were obtained for black/white images. Scrambled stimuli in each
      study yielded no valence effects but demonstrated typical P300 topography that
      increased from frontal to parietal areas. The findings suggest that P300
      amplitude is sensitive to affective picture valence in the absence of stimulus
      arousal differences, and that stimulus color contributes to ERP valence effects.

PMID- 18708100
TI  - Individual differences in fear-potentiated startle as a function of resting heart
      rate variability: implications for panic disorder.
AB  - BACKGROUND: Anticipatory anxiety, which can be indexed by the startle
      potentiation to a threat of shock, has been implicated in the development of
      panic disorder. Large individual differences exist in startle potentiation to
      threat of shock but few differences have been found between panic patients in
      general and non-anxious controls. The present studies explored resting heart rate
      variability (HRV) as a source of individual differences in startle potentiation
      in students at risk for panic disorder and in unmedicated panic patients.
      METHODS: Participants in Study 1 were 22 students high and 21 students low in
      anxiety sensitivity (AS). Nine unmedicated panic patients and 15 matched non
      anxious controls were included in Study 2. Startle potentiation to the threat of
      shock was examined as a function of AS (Study 1) and diagnostic category (Study
      2) as well as resting HRV. RESULTS: Whereas no differences in startle
      potentiation were found as a function of AS or panic disorder diagnosis in
      general, both studies revealed that low resting HRV was associated with
      exaggerated startle responses to the threat of shock. CONCLUSIONS: The present
      results replicate and extend the sparse literature on fear-potentiated startle in
      panic disorder. Low HRV was associated with more pronounced startle potentiation
      to both explicit and contextual cues. Thus, low HRV may be a useful endophenotype
      for at least some anxiety disorders.

PMID- 18708101
TI  - EEG coherence in girls with attention-deficit/hyperactivity disorder: stimulant
      effects in good responders.
AB  - This study investigated the effects of stimulants on EEG coherence in girls with
      Attention-Deficit/Hyperactivity Disorder (AD/HD). Twenty girls with AD/HD (aged 7
      12) and 20 age- and sex-matched controls had an eyes-closed resting
      electroencephalogram (EEG) recorded from 21 electrode sites. Coherence was
      calculated from eight intrahemispheric electrode pairs (four in each hemisphere),
      and eight interhemispheric electrode pairs, for the delta, theta, alpha and beta
      frequency bands. AD/HD participants were tested twice: first, prior to medication
      being prescribed, and second, six months later on a therapeutic dose of a
      stimulant. With intrahemispheric coherences at short-medium inter-electrode
      distances, AD/HD girls off-medication had reduced lateralisation in the delta,
      theta and alpha bands. They also had reduced lateralisation in the theta band for
      longer inter-electrode distances, and increased frontal interhemispheric
      coherences in all frequency bands. Medication had no impact on the laterality
      anomalies, but produced novel increases in intrahemispheric coherences at short
      medium inter-electrode distances, which reached significance in the delta band
      and approached significance in the alpha band. However, these increased
      coherences remained indistinguishable from control levels. Reduced hemispheric
      lateralisations found in these AD/HD participants illustrate cortical
      abnormalities consistent with maturational lag explanations. The widespread
      elevated frontal interhemispheric coherences found in these AD/HD girls could
      reflect the narrow profile of female medication responders identified in clinical
      settings. The lack of substantial coherence medication effects in good clinical
      responders supports a previous medication study with AD/HD boys, and suggests
      that these coherence anomalies reflect structural, rather than solely functional,
      differences in brain development in AD/HD.

PMID- 18708102
TI  - The validity of finger pulse line length for the detection of concealed
      information.
AB  - Building on the orienting theory of the Concealed Information Test, Elaad and Ben
      Shakhar [Elaad, E., & Ben-Shakhar, G. (2006). Finger pulse waveform length in the
      detection of concealed information. Int. J. Psychophysiol., 61, 226-234.]
      proposed a new measure for the detection of concealed information: finger pulse
      line length (FPLL). This measure is recorded with a plethysmograph and combines
      pulse rate and pulse amplitude. Because the validity of finger pulse amplitude is
      still not established, one could question the benefits of FPLL to well validated
      measures such as heart rate. In the present study we compared the validity of
      FPLL, finger pulse rate and finger pulse amplitude in the detection of concealed
      information. Male community volunteers (n=77) who had acquired crime knowledge
      through a mock crime procedure, were instructed to deny knowledge in a Concealed
      Information Test. Skin conductance, finger pulse line length, finger pulse rate
      and amplitude, heart rate and respiration were recorded. FPLL validity was
      significantly higher than that of finger pulse amplitude and heart rate. These
      data, together with its ease of measurement, support the use of FPLL.

PMID- 18708103
TI  - Somatosensory evoked magnetic fields following electric tongue stimulation using
      pin electrodes.
AB  - Quantitative evaluation of the sensory disturbance of the tongue is important
      clinically. However, because the conventional electrophysiological approach to
      the peripheral nerve cannot be used in the mandible owing to the deep route of
      the lingual nerve, we applied evoked potentials in the central nervous system.
      Somatosensory evoked magnetic fields (SEFs) following electric stimulation were
      recorded in 10 healthy subjects by means of pin electrodes placed on the tongue
      mucosa. Three or four components (P25m, P40m, P60m, and P80m) were identified
      over the contralateral hemisphere with unilateral stimulation. Because none of
      the components were consistently detected in all subjects, we evaluated the root
      mean square (RMS) of 18 channels over the contralateral hemisphere. To estimate
      the activated cortical response, we calculated the difference in mean RMS
      amplitude between 10 and 150 ms and that of the baseline period (aRMS=RMS[10,
      150]-RMS[-50, -5]). The aRMS values for right-sided and left-sided stimulation
      were 10.18+/-7.92 and 10.99+/-8.98 fT/cm, respectively, and the mean laterality
      index, expressed by [(left-right)/(left+right)] was 0.025+/-0.104. This parameter
      can be useful for evaluating patients with unilateral sensory abnormality of the
      tongue.

PMID- 18708104
TI  - Acute and chronic responses associated with adrenomedullin administration in
      experimental colitis.
AB  - Adrenomedullin (AM) is a 52 amino acid peptide and member of the calcitonin gene
      related peptide (CGRP) super family. Given that AM has emerged as a potential
      immuno-regulatory and anti-inflammatory agent in various experimental models,
      this study has deepened into its possible therapeutic effect in intestinal
      inflammation analyzing the responses in both acute and chronic (14 and 21 days)
      phases of TNBS-induced colitis in rats. In the acute model, AM treatment reduced
      the incidence of diarrhea and the severity of colonic damage, and improved the
      survival rate at the three doses assayed (50, 100, and 200ng/kg animal). AM
      administration was able to reduce the early production of TNF-alpha and
      collaborated to maintaining basal levels of IFN-gamma and IL-10. In the chronic
      studies the peptide attenuated the extent of the damage with lesser incidence of
      weight loss and diarrhea (50 and 100ng/kg animal). Cellular neutrophil
      infiltration, with the subsequent increase in myeloperoxidase (MPO) levels caused
      by TNBS, was reduced after chronic AM administration. The peptide played a role
      in the evolution of Th1/Th2 cytokines balance and chronic disease recuperation:
      levels of proinflammatory TNF-alpha and IFN-gamma decreased and anti-inflammatory
      IL-10 increased significantly. Cyclooxygenase-2 (COX-2) and nitric oxide synthase
      (iNOS) protein expression were not modified by AM administration, although a
      reduction of nitric oxide (NO) production could be detected in the chronic model.
      These results support a role of AM as an anti-inflammatory factor with beneficial
      effects in intestinal inflammatory colitis.

PMID- 18708105
TI  - A biologically active rhIGF-1 fusion accumulated in transgenic rice seeds can
      reduce blood glucose in diabetic mice via oral delivery.
AB  - Human insulin-like growth factor 1(hIGF-1) is essential for cell proliferation
      and used therapeutically in treating various diseases including diabetes
      mellitus. Here, we present that a recombinant hIGF-1(rhIGF-1) was expressed fused
      with the C-terminus of a rice luminal binding protein and accumulated highly in
      rice seeds, reaching 6.8+/-0.5% of total seed protein. The rhIGF-1 fusion was
      demonstrated to possess biological activity to stimulate cell proliferation.
      Importantly, the unprocessed transgenic seeds could significantly increase plasma
      rhIGF-1 level and reduce blood glucose of diabetic mice via oral delivery.
      Further studies suggested that transgenic seeds reduced blood glucose of diabetic
      mice by enhancing islet cells survival and increasing insulin secretion rather
      than increasing insulin sensitivity. These results indicated the potential of the
      novel fusion expression system in production and oral delivery of biologically
      active small peptides for diseases.

PMID- 18708107
TI  - Baculovirus surface display of E2 envelope glycoprotein of classical swine fever
      virus and immunogenicity of the displayed proteins in a mouse model.
AB  - Classical swine fever virus (CSFV) causes significant losses in pig industry in
      many countries. The E2 glycoprotein of CSFV is the main target for inducing
      neutralizing antibodies and protective immunity in the natural host. In this
      study, one recombinant baculoviruses BacSC-E2 expressing histidine-tagged E2 with
      the CTD and TM derived from baculovirus envelope protein gp64 was constructed and
      evaluated its vaccine efficacy in mice model. After infection, E2 was expressed
      and anchored on the plasma membrane of Sf-9 cells, as revealed by confocal
      microscopy. Immunogold electron microscopy demonstrated that the BacSC-E2 was
      displayed E2 glycoprotein on the viral surface. Animal vaccine tests showed that
      BacSC-E2 elicited significantly higher E2 antibody titers in the treated mouse
      models than the control group. Virus neutralization test showed that serum from
      the BacSC-E2 treated models had significant levels of virus neutralization
      activities. This demonstrates that the BacSC-E2 vaccine can be a potential
      vaccine against CSFV infections. This is the first report demonstrating that the
      potential of E2-pseudotyped baculovirus as a classical swine fever virus vaccine.

PMID- 18708108
TI  - Electroporation-based DNA transfer enhances gene expression and immune responses
      to DNA vaccines in cattle.
AB  - Despite the potential of DNA vaccines to induce strong, balanced immune responses
      in small experimental species, the immune responses to DNA immunization in larger
      species have generally been moderate and inconsistent. In this study, the
      TriGridtrade mark Delivery System (TDS), an electroporation-based DNA delivery
      platform, was evaluated for administration of DNA vaccines to calves. When
      compared to conventional intramuscular delivery, TDS-based delivery markedly and
      consistently enhanced gene expression from a plasmid encoding a reporter gene,
      secreted alkaline phosphatase, and improved cell-mediated and humoral immune
      responses to a plasmid encoding a model antigen, hepatitis B surface antigen.
      Importantly, the TDS-based procedure was well tolerated by the calves, which did
      not need to be anesthetized or sedated. These results suggest that the TDS is a
      useful delivery method for DNA vaccines in cattle.

PMID- 18708106
TI  - Live, attenuated influenza virus (LAIV) vehicles are strong inducers of immunity
      toward influenza B virus.
AB  - Historically, vaccines developed toward influenza viruses of the B type using
      methodologies developed for influenza A viruses as a blueprint have not been
      equally efficacious or effective. Because most influenza research and public
      attention concerns influenza A viruses, these shortcomings have not been
      adequately addressed. In this manuscript, we utilized different influenza vaccine
      vehicles to compare immunogenicity and protection in mice and ferrets after
      vaccination against an influenza B virus. We report that plasmid DNA vaccines
      demonstrate low immunogenicity profiles and poor protection compared to either
      whole, inactivated influenza virus (IIV) or, live, attenuated influenza virus
      (LAIV) vaccines. When mixed prime:boost regimens using LAIV and IIV were studied,
      we observed a boosting effect in mice after priming with LAIV that was not seen
      when IIV was used as the prime. In ferrets LAIV induced high antibody titers
      after a single dose and provided a boost in IIV-primed animals. Regimens
      including LAIV as a prime demonstrated enhanced protection, and adjuvantation was
      required for efficacy using the IIV preparation. Our results differ from
      generally accepted influenza A virus vaccine models, and argue that strategies
      for control of influenza B virus should be considered separately from those for
      influenza A virus.

PMID- 18708109
TI  - Perspectives on advancing preventative medicine through vaccinology at the
      comparative veterinary, human and conservation medicine interface: not missing
      the opportunities.
AB  - Vaccination has historically and remains one of the most cost-effective and
      safest forms of medicine today. Along with basic understanding of germ theory and
      sanitation, vaccination, over the past 50 years, has transformed lives and
      economies in both rich and poor countries by its direct impact on human and
      animal life--resulting in the eradication of small pox, huge reductions in the
      burden of previously common human and animal diseases such as polio, typhoid,
      measles in human medicine and contagious bovine pleuropneumonia, foot-and-mouth
      disease, screwworm and hog cholera and the verge of eradicating brucellosis,
      tuberculosis, and pseudorabies in veterinary medicine. In addition vaccination
      along with other animal production changes has provided the ability to produce
      otherwise unaffordable animal protein and animal health worldwide. The landscape
      however on which vaccinology was discovered and applied over the past 200 years,
      even in the past 10 years has and is undergoing continuous change. For
      vaccination as a public health tool to have its greatest impacts in human and
      veterinary medicine, these great medical sciences will have to come together,
      policy-relevant science for sustainable conservation in developing and developed
      countries needs to become the norm and address poverty (including lack of basic
      health care) in communities affected by conservation, and to consider costs and
      benefits (perceived or not) affecting the well-being of all stakeholders, from
      the local to the multinational. The need to return to and/or develop new
      education-based models for turning the tide from the heavily return-on-investment
      therapeutic era of the last century into one where the investment into the
      preventative sciences and medicine lead to sustainable cultural and cost
      effective public health and economic changes of the future is never more evident
      than today. The new complex problems of the new millennium will require new
      educational models that train para- and professional people for thinking and
      solving complex inter-related biological, ecological, public-, political/economic
      problems. The single profession that is best positioned to impact vaccinology is
      Veterinary Medicine. It's melding with human medicine and their role in future
      comparative and conservation-based programs will be critical to the successful
      application of vaccines into the 21st century.

PMID- 18708110
TI  - Role of different genes in the CS6 operon for surface expression of
      Enterotoxigenic Escherichia coli colonization factor CS6.
AB  - Coli surface antigen 6, CS6, is one of the most prevalent colonization factors
      (CFs) associated with Enterotoxigenic Escherichia coli (ETEC) bacteria, the most
      common cause of diarrhea among infants and children in developing countries. The
      CS6 operon encodes two structural subunit proteins, CssA and CssB, a chaperon,
      CssC, and an usher, CssD. Since little is known about the relationship of the
      genes and their role in expression and surface assembly of CS6, the operon was
      cloned into a laboratory E. coli strain, and mutants were constructed by creating
      deletions in each of the genes. Examination of protein expression by different
      methods, using monoclonal antibodies with specificities for the individual CS6
      structural proteins, suggested that the usher (CssD) was not involved in assembly
      or surface expression of CS6 whereas deletion of the chaperon (CssC)
      significantly reduced levels of CssA, but not of CssB. Binding studies with CaCo
      2 cells demonstrated that there is a combined effect of CssC and CssD on receptor
      binding, presumably associated with their activities in assembly and transport of
      the structural subunits. These findings may have important implications for the
      construction of strains expressing high levels of CS6 on the surface for eventual
      use in an ETEC vaccine.

PMID- 18708111
TI  - The role of economic information in decision-making by the Advisory Committee on
      Immunization Practices.
AB  - With cost of vaccines steadily increasing, recommendations of the Advisory
      Committee on Immunization Practices (ACIP) have growing economic implications for
      the public. We used semi-structured telephone interviews to assess the knowledge,
      attitudes, and practices of the 15 voting members of the 2006-2007 ACIP regarding
      the use of economic information by the committee in their deliberations about new
      vaccine recommendations. These interviews demonstrated the importance of economic
      information in ACIP deliberations, but also revealed that many members felt
      economic information should not be outweighed by the more important issues of
      vaccine efficacy, disease burden, and safety. In addition, though members had
      variable levels of expertise in analyzing economic data, there was a general
      concern that assumptions inherent in the development of cost-effectiveness models
      made interpretation of the data resulting from these models difficult. To
      counteract this concern, several ACIP members suggested standardizing the process
      of how economic data are presented to the committee so that a more uniform
      consideration of consequential information might be undertaken by the ACIP in
      their deliberations.

PMID- 18708112
TI  - Isolation of rifampicin resistant Flavobacterium psychrophilum strains and their
      potential as live attenuated vaccine candidates.
AB  - Previous studies have demonstrated that passage of pathogenic bacteria on
      increasing concentrations of the antibiotic rifampicin leads to the attenuation
      of virulence and these resistant strains may serve as live attenuated vaccines.
      Two rifampicin resistant strains of Flavobacterium psychrophilum, 259-93A.16 and
      259-93B.17, were generated by passage on TYES plates containing increasing
      concentrations of rifampicin. Electrophoretic analysis of whole-cell lysates
      prepared from the parent and resistant strains identified five differentially
      expressed proteins between the 259-93B.17 strain and parent strain, while there
      were no differences identified between the 259-93A.16 and parent strain. The LPS
      banding patterns were identical between all three strains. Bacterial challenges
      of rainbow trout (Oncorhynchus mykiss Walbaum) with the resistant strains
      demonstrated that the 259-93B.17 strain was highly attenuated and the 259-93A.16
      strain was modestly attenuated at the challenge doses tested. Immunization of
      rainbow trout with the live attenuated 259-93B.17 strain by intraperitoneal
      injection resulted in significant protection against challenge with the virulent
      parent F. psychrophilum strain at 8 and 15 weeks post-immunization and fish
      exhibited elevated specific antibody titers. Importantly, immersion delivery of
      the 259-93B.17 strain stimulated protective immune responses in fish at 10 weeks
      post-immunization. The results demonstrate that the rifampicin resistant 259
      93B.17 strain may serve as an effective live attenuated vaccine for the
      prevention of F. psychrophilum infections.

PMID- 18708113
TI  - Induction of HIV-1 MPR(649-684)-specific IgA and IgG antibodies in caprine
      colostrum using a peptide-based vaccine.
AB  - Induction of antigen-specific antibodies against HIV-1 in colostrum and milk may
      help prevent breast milk transmission of the virus. A peptide vaccine against the
      HIV-1 gp41 membrane proximal region (MPR(649-684)) was evaluated as proof-of
      principle in a caprine model. Pregnant Alpine/Saanen goats were immunized with
      MPR(649-684) peptide conjugated to KLH using alum adjuvant. Immunizations were
      intramuscular, intranasal, and in the supramammary lymph node region. Samples
      collected after parturition demonstrated the presence of MPR(649-684)-specific
      antibodies in colostrum and serum. These results support the concept that a
      peptide vaccine can effectively induce MPR(649-684)-specific sIgA and IgG in the
      colostrum of a lactating species.

PMID- 18708115
TI  - Current codex guidelines for assessment of potential protein allergenicity.
AB  - A rigorous safety assessment process exists for GM crops. It includes evaluation
      of the introduced protein as well as the crop containing such protein with the
      goal of demonstrating the GM crop is "as-safe-as" non-transgenic crops in the
      food supply. One of the major issues for GM crops is the assessment of the
      expressed protein for allergenic potential. Currently, no single factor is
      recognized as an identifier for protein allergenicity. Therefore, a weight-of
      evidence approach, which takes into account a variety of factors and approaches
      for an overall assessment of allergenic potential, is conducted [Codex
      Alimentarious Commission, 2003. Alinorm 03/34: Joint FAO/WHO Food Standard
      Programme, Codex Alimentarious Commission, Twenty-Fifth Session, Rome, Italy, 30
      June-5 July, 2003. Appendix III, Guideline for the conduct of food safety
      assessment of foods derived from recombinant-DNA plants, and Appendix IV, Annex
      on the assessment of possible allergenicity, pp. 47-60]. This assessment is based
      on what is known about allergens, including the history of exposure and safety of
      the gene(s) source; protein structure (e.g., amino acid sequence identity to
      human allergens); stability to pepsin digestion in vitro [Thomas, K. et al.,
      2004. A multi-laboratory evaluation of a common in vitro pepsin digestion assay
      protocol used in assessing the safety of novel proteins. Regul. Toxicol.
      Pharmacol. 39, 87-98]; an estimate of exposure of the novel protein(s) to the
      gastrointestinal tract where absorption occurs (e.g., protein abundance in the
      crop, processing effects); and when appropriate, specific IgE binding studies or
      skin prick testing. Additional approaches may be considered (e.g., animal models;
      targeted sera screening) as the science evolves; however, such approaches have
      not been thoroughly evaluated or validated for predicting protein allergenicity.

PMID- 18708114
TI  - Inhaled delivery of 23-valent pneumococcal polysaccharide vaccine does not result
      in enhanced pulmonary mucosal immunoglobulin responses.
AB  - We compared the effect of intramuscular vs. inhaled 23-valent pneumococcal
      capsular polysaccharide vaccine (23-PPV) on pulmonary mucosal immunoglobulin
      levels. Bronchoalveolar lavage (BAL) and serum were collected from 33 adults
      before and 1 month after injected (n=16) or inhaled (n=17) 23-PPV. Levels of
      pneumococcal capsule-specific IgG and IgA to types 1, 9V and 14 were measured in
      each sample. Injected 23-PPV produced a significant increase in types 1, 9V and
      14 capsule-specific IgG and type 1 IgA in both serum and BAL (type 1 geometric
      mean BAL IgG 9.8 ng/ml post-vaccine vs. 5 ng/ml pre-vaccine, p=0.01; type 9V geo
      mean 5.6 ng/ml vs. 2.7 ng/ml, p=0.001; type 14 geo mean 23.6 ng/ml vs. 6.2 ng/ml,
      p=0.02). Inhaled vaccine produced no response in either BAL or serum.

PMID- 18708116
TI  - Cytokine profiling of chemical allergens in mice: measurement of message versus
      protein.
AB  - Chemical respiratory allergy is an important occupational health problem, but
      there are currently available no validated methods for hazard identification.
      There has been interest for some time in the application of cytokine profiling
      for the characterization of chemical allergens. We have now examined whether
      these cytokine expression patterns are regulated at the level of mRNA and/or
      protein production. Mice (BALB/c strain) were exposed topically to the contact
      allergen 2,4-dinitrochlorobenzene (DNCB), or to the respiratory allergen
      trimellitic anhydride (TMA). Thirteen days after the initiation of exposure, a
      single cell suspension of draining (auricular) lymph node cells (LNC) was
      prepared. Cells were cultured for 24-120h and supernatants analyzed for cytokine
      protein by cytokine bead array. In parallel experiments total RNA was prepared
      from freshly isolated or cultured cells and cytokine gene expression was analyzed
      by ribonuclease protection assay (RPA) or by real time reverse transcription
      polymerase chain reaction (RT-PCR). DNCB-activated LNC secreted high levels of
      the type 1 cytokines interferon (IFN)-gamma and IL-12 compared with TMA
      stimulated LNC. The converse type 2 pattern was observed following treatment with
      TMA. Freshly isolated LNC from TMA-treated mice displayed a selective type 2
      cytokine mRNA profile as measured by RPA. In contrast, RNA isolated from DNCB
      activated LNC displayed a more mixed cytokine phenotype with relatively low
      levels of transcripts for both type 1 and type 2 cell products. When cytokine
      gene expression was measured by the more sensitive real time RT-PCR technique,
      more vigorous expression of IL-4 was recorded for TMA-activated LNC compared with
      DNCB-activated LNC but there was no evidence for elevated IFN-gamma transcripts
      for the latter treatment. The observation that IFN-gamma mRNA expression is not
      increased in DNCB-activated LNC despite robust secretion of this cytokine
      indicates that production is controlled mainly at the level of translation of
      previously transcribed mRNA or of protein secretion. Furthermore, the
      preferential cytokine profile recorded following TMA exposure was more clearly
      contrasting when measured at the level of protein secretion rather than at the
      level of mRNA expression. Experience to date suggests that the measurement of
      induced cytokine profiles shows promise for the hazard identification and
      characterization of chemical respiratory allergens, and that the end point best
      suited for this purpose is cytokine secretion rather than mRNA expression.

PMID- 18708117
TI  - Cellular accumulation and distribution of uranium and lead in osteoblastic cells
      as a function of their speciation.
AB  - Uranium (U) and lead (Pb) are accumulated and fixed for long periods in bone,
      impairing remodeling processes. Their toxicity to osteoblasts, the cells
      responsible for bone formation, is poorly documented. It has been previously
      shown that cytotoxicity and phenotypic effects of both metals on osteoblasts are
      highly influenced by metal speciation. Differences in sensitivity between cell
      types have been underlined as well. In this paper, cellular accumulation of U and
      Pb in cultured and primary osteoblastic cells was assessed by trace element
      analysis. Distribution of different species at the cell scale was investigated by
      electron microscopy. Internalization of both metals was shown to be correlated to
      cytotoxicity and population growth recovery after exposure. For each metal, the
      amount of metal uptake leading to 50% cell death was shown to be speciation
      dependent. Scanning and transmission electron microscopy showed the formation of
      precipitates with phosphate in lysosomes for both metals, whose role in toxicity
      or cell defence remains to be clarified. Although a clear link was established
      between cytotoxicity and accumulation, differences in sensitivity observed in
      terms of speciation could not be fully explained and other studies seem
      necessary.

PMID- 18708118
TI  - Editorial introduction to the special issue on bio(nano)materials with structure
      property relationship.

PMID- 18708119
TI  - Human microvascular endothelial cells are sensitive to IGF-I but resistant to
      insulin at the receptor level.
AB  - Human microvascular endothelial cells (HMVEC) are sensitive to IGF-I but insulin
      resistant and express several times more IGF-I receptors (IGF-IR) than insulin
      receptors (IR). Our aim was to investigate the mechanism of this insulin
      resistance in cultured HMVEC by studying receptor activation and signal
      propagation downstream. The IGF-IR beta-subunit and the IR beta-subunit were
      detected and found to co-precipitate. IRA was the major IR isoform expressed in
      HMVEC. IGF-I 10(-9) to 10(-8)M phosphorylated its cognate receptor beta-subunit.
      IGF-I also phosphorylated the IR beta-subunit at 10(-9)M. Phosphorylation of
      insulin receptor substrate 1 was obtained by IGF-I 10(-9) to 10(-8)M. Akt was
      phosphorylated by IGF-I at 10(-8) to 10(-7)M and by insulin 10(-7)M. IGF-I at 10(
      8) to 10(-6)M significantly increased DNA-synthesis. We conclude that
      microvascular endothelial cells are sensitive to IGF-I but resistant to insulin
      due to a preponderance of IGF-I receptors and sequestration of insulin receptors
      into insulin/IGF-I hybrid receptors.

PMID- 18708120
TI  - Presynaptic large-conductance calcium-activated potassium channels control
      synaptic transmission in the superficial dorsal horn of the mouse.
AB  - Large-conductance calcium-activated potassium channels (BK channels) have been
      suggested to play a substantial role in synaptic transmission in the spinal cord
      dorsal horn. In the present experiments, we attempted to clarify the
      physiological significance of BK channels in the modulation of synaptic
      transmission in the superficial dorsal horn where nociceptive information is
      processed. Spontaneously occurring excitatory postsynaptic currents (sEPSCs) were
      recorded from the neurons located in the superficial dorsal horn of a mouse
      spinal cord slice, and the effects of iberiotoxin, a BK channel blocker, on
      sEPSCs were analyzed. The frequency of sEPSCs was significantly higher in the
      peripheral nerve-ligated neuropathic mice than in the sham-operated control mice,
      but the amplitude of sEPSCs was equivalent between the two groups. Iberiotoxin
      increased the frequency of sEPSCs in the control mice to the same level as that
      in the neuropathic mice without affecting the amplitude of sEPSCs. In contrast,
      iberiotoxin did not show any significant effects on the sEPSCs in the neuropathic
      mice. These findings suggest that the BK channels that are located in presynaptic
      terminals control synaptic transmission in the superficial dorsal horn, and that
      functional downregulation of BK channels accompanies the neuropathic pain induced
      by peripheral nerve injury. This downregulation was confirmed by real-time
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of
      the BK channel alpha subunit. Taken together, our present results indicate that
      BK channels play crucial roles in the synaptic transmission of nociceptive
      information in the superficial dorsal horn.

PMID- 18708121
TI  - Chemosensory induced arousals during sleep in premenopausal women.
AB  - Only a limited number of studies is available addressing chemosensory stimulation
      during sleep. Recent work indicates that stimulation with a nasal irritant
      produces an increase in arousal frequency in non-REM sleep, whereas a selective
      olfactory stimulant does not. The present study focused on arousal reactions in
      REM sleep. Five young healthy volunteers were investigated during 27 nights.
      Using air-dilution olfactometry CO(2) was used for nasal irritation and H(2)S was
      used as a specific olfactory stimulant. Both stimuli were presented at four
      concentrations, odorless stimuli served as control. Other than in previous
      studies arousal latency was used as a dependent measure. Even the strongest
      olfactory stimulus did not produce an increase in arousal frequency in REM sleep
      whereas for irritation such an increase was clearly present. Latencies of arousal
      responses to CO(2) shortened with increasing stimulus concentrations. Olfactory
      stimulation does not lead to arousal reactions. In contrast, trigeminal
      stimulation produces a concentration-dependent increase in arousal frequency and
      decrease in arousal latency across all sleep stages. The present data shows for
      the first time that arousals are not present during REM sleep in response to
      selective olfactory stimuli. However, such changes are easily evoked by irritants
      activating the trigeminal nerve.

PMID- 18708122
TI  - Early reaction of astroglial cells in rat hippocampus to streptozotocin-induced
      diabetes.
AB  - Diabetic patients show impaired brain functions, although underlying mechanisms
      remain unclear. Little is known as well about early diabetes-related changes in a
      brain tissue. To investigate them we analyzed the reaction of astroglial cells in
      the hippocampus of rats rendered diabetic by a single injection of streptozotocin
      (STZ). Astrocyte count, size and shape as well as levels of glial fibrillary
      acidic protein (GFAP) and S100b protein were assessed 3, 7 and 14 days after the
      STZ injection using immunohistochemistry, immuno-enzyme assay and computer
      assisted image analysis. The reduced GFAP-positive cell count was found on day 3
      when these cells were significantly smaller and less arborized with respect to
      the control. This tendency reversed on day 7 when more numerous GFAP-positive
      cells grew in size and became more ramified. S100b-positive cell count changes
      followed a contrasting pattern, elevating on days 3 and 7 and dropping on day 14.
      The level of cytoskeletal GFAP changed in parallel with GFAP expression revealed
      by immunocytochemistry, while cytosolic GFAP level started to increase only 7
      days after the STZ injection. At the same time S100b level experienced an
      elevation on day 3 reaching the peak on day 7 and decreasing afterwards. These
      results suggest that the reaction of astroglial cells may be the earliest
      response of the brain tissue to an altered glucose metabolism playing presumably
      the critical role in the mechanisms underlying diabetes-related impairments of
      brain functions.

PMID- 18708123
TI  - The LARK/RBM4a protein is highly expressed in cerebellum as compared to cerebrum.
AB  - The RNA binding motif protein 4 genes RBM4a and RBM4b are located on human
      chromosome 11q13.2 and encode highly similar proteins of 363 and 359 amino acids,
      respectively. They contain two RNA recognition motifs (RRMs) and a retroviral
      type Zn-finger. RBM4a binds RNA, is involved in alternative splicing and is also
      a part of the microRNA-processing RISC complex. In particular, RBM4a is involved
      in exon 10 inclusion of the tau protein. The function of RBM4b is unknown. With
      new monoclonal antibodies we show that RBM4a is detectable in virtually all
      tissues and cell lines tested while RBM4b was only found in kidney and liver.
      Both RBM4a and RBM4b are nuclear phosphoproteins with half-lives of 2.5h and
      4.5h, respectively. To our knowledge, this is the first description of RBM4b
      protein in human tissue. In human brain, expression of RBM4a was strongly up
      regulated in cerebellum as compared to forebrain.

PMID- 18708124
TI  - A SARS-CoV protein, ORF-6, induces caspase-3 mediated, ER stress and JNK
      dependent apoptosis.
AB  - Severe acute respiratory syndrome (SARS) coronavirus (CoV) spread from China to
      more than 30 countries, causing severe outbreaks of atypical pneumonia and over
      800 deaths worldwide. CoV primarily infects the upper respiratory and
      gastrointestinal tract; however, SARS-CoV has a unique pathogenesis because it
      infects both the upper and lower respiratory tracts and leads to human
      respiratory diseases. SARS-CoV genome has shown containing 14 open reading frames
      (ORFs) and 8 of them encode novel proteins. Previous reports show that
      overexpression of ORF-3a, ORF-3b and ORF-7a induce apoptosis. In this report, we
      demonstrate that overexpression of ORF-6 also induces apoptosis and that Caspase
      3 inhibitor and JNK inhibitor block ORF-6 induced apoptosis. Importantly, the
      protein level of ER chaperon protein, GRP94, was up-regulated when ORF-6 was
      overexpressed. All these data suggest that ORF-6 induces apoptosis via Caspase-3
      mediated, ER stress and JNK-dependent pathways.

PMID- 18708125
TI  - The alpha-L-Rhamnose recognizing lectin site of human dermal fibroblasts
      functions as a signal transducer: modulation of Ca2+ fluxes and gene expression.
AB  - An alpha-l-Rhamnose specific lectin site was described on human skin
      keratinocytes and fibrobasts. The addition of Rhamnose-rich oligo- and
      polysaccharides (RROPs) to fibroblasts has been shown to stimulate cell
      proliferation and increase extracellular matrix biosynthesis, suggesting that
      this lectin site functions as a "true" receptor transmitting messages to the cell
      interior. It was confirmed here that addition of the Rhamnose-rich
      polysaccharide, RROP-1, to normal human dermal fibroblasts (NHDFs) and human
      endothelial cells produced a dose-dependent stimulation of the calcium-signaling
      pathway, inducing fast and transient increases in Ca2+ influx and intracellular
      free Ca2+ level. The Rhamnose-rich oligosaccharide RROP-3 as well as l-Rhamnose
      alone were also able to trigger similar intracellular free Ca2+ concentration
      increases in NHDFs. Moreover, the recording of the RROP-1-induced modification of
      the gene-expression profile in fibroblasts showed that this polysaccharide
      triggered a down-regulation of the expression of several growth factors, adhesion
      molecules and extracellular matrix proteins involved in pro-tumoral activity
      and/or fibrotic processes. These results further support the hypothesis of a
      receptor function for the Rhamnose-recognizing lectin site in fibroblasts. Anti
      fibrotic and anti-tumoral potential of RROP-1 remains to be further explored.

PMID- 18708127
TI  - Visual experience regulates Kv3.1b and Kv3.2 expression in developing rat visual
      cortex.
AB  - Among the GABAergic neocortical interneurons, parvalbumin-containing fast-spiking
      (FS) basket cells are essential mediators of feed-forward inhibition, network
      synchrony and oscillations, and timing of the critical period for sensory
      plasticity. The FS phenotype matures after birth. It depends on the expression of
      the voltage-gated potassium channels Kv3.1b/3.2 which mediate the fast membrane
      repolarization necessary for firing fast action potentials at high frequencies.
      We have now tested in rat visual cortex if visual deprivation affects the Kv3
      expression. During normal development, Kv3.1b/3.2 mRNA and protein expression
      increased in rat visual cortex reaching adult levels around P20. Dark rearing
      from birth neither prevented nor delayed the upregulation. Rather unexpectedly,
      the expression of Kv3.1b protein and Kv3.2 mRNA and protein increased to higher
      levels from the third postnatal week onwards. Triple-labeling revealed that in
      dark-reared visual cortex Kv3.2 was upregulated in parvalbuminergic interneurons
      in supragranular layers which in normal animals rarely display Kv3.2 expression.
      Recovery from dark rearing normalized Kv3.2 expression. This showed that visual
      experience influences the Kv3 expression. The results suggest that an altered
      expression of Kv3 channels affects the functional properties of FS neurons, and
      may contribute to the deficits in inhibition observed in the sensory-deprived
      cortex.

PMID- 18708126
TI  - The role of macrophages in optic nerve regeneration.
AB  - Following injury to the nervous system, the activation of macrophages, microglia,
      and T-cells profoundly affects the ability of neurons to survive and to
      regenerate damaged axons. The primary visual pathway provides a well-defined
      model system for investigating the interactions between the immune system and the
      nervous system after neural injury. Following damage to the optic nerve in mice
      and rats, retinal ganglion cells, the projection neurons of the eye, normally
      fail to regenerate their axons and soon begin to die. Induction of an
      inflammatory response in the vitreous strongly enhances the survival of retinal
      ganglion cells and enables these cells to regenerate lengthy axons beyond the
      injury site. T cells modulate this response, whereas microglia are thought to
      contribute to the loss of retinal ganglion cells in this model and in certain
      ocular diseases. This review discusses the complex and sometimes paradoxical
      actions of blood-borne macrophages, resident microglia, and T-cells in
      determining the outcome of injury in the primary visual pathway.

PMID- 18708129
TI  - Transgenic overexpression of corticotropin releasing hormone provides partial
      protection against neurodegeneration in an in vivo model of acute excitotoxic
      stress.
AB  - Corticotropin releasing hormone (CRH) is the central modulator of the mammalian
      hypothalamic-pituitary-adrenal (HPA) axis. In addition, CRH affects other
      processes in the brain including learning, memory, and synaptic plasticity.
      Moreover, CRH has been shown to play a role in nerve cell survival under
      apoptotic conditions and to serve as an endogenous neuroprotectant in vitro.
      Employing mice overexpressing murine CRH in the CNS, we observed a differential
      response of CRH-overexpressing mice (CRH-COEhom-Nes) to acute excitotoxic stress
      induced by kainate compared with controls (CRH-COEcon-Nes). Interestingly, CRH
      overexpression reduced the duration of epileptic seizures and prevented kainate
      induced neurodegeneration and neuroinflammation in the hippocampus. Our findings
      highlight a neuroprotective action of CRH in vivo. This neuroprotective effect
      was accompanied by increased levels of brain-derived neurotrophic factor (BDNF)
      in CRH-COEhom-Nes mice, suggesting a potential role for BDNF in mediating CRH
      induced neuroprotective actions against acute excitotoxicity in vivo.

PMID- 18708128
TI  - Duration of binocular decorrelation in infancy predicts the severity of
      nasotemporal pursuit asymmetries in strabismic macaque monkeys.
AB  - PURPOSE: Strabismus in human infants is linked strongly to nasotemporal
      asymmetries of smooth pursuit, but many features of this co-morbidity are
      unknown. The purpose of this study was to determine how the duration of early
      onset strabismus (or timeliness of repair) affects the severity of pursuit
      asymmetries in a primate model. METHODS: Binocular image decorrelation was
      imposed on infant macaques by fitting them with prism goggles on day 1 of life.
      The goggles were removed after 3 weeks (n=2), 12 weeks (n=2) or 24 weeks (n=3),
      emulating surgical repair of strabismus in humans at 3, 12, and 24 months of age,
      respectively. Two control monkeys wore plano lenses. Several months after the
      goggles were removed, horizontal smooth pursuit was recorded using binocular
      search coils and a nasal-bias index (NBI) was calculated. RESULTS: Each animal in
      the 12- and 24-week groups developed a constant, alternating esotropic strabismus
      and a nasotemporal asymmetry of pursuit when viewing with either eye. Spatial
      vision was normal (no amblyopia). The 3-week duration monkeys were
      indistinguishable from control animals; they had normal eye alignment and
      symmetric pursuit. In the 12- and 24-week monkeys, the longer the duration of
      binocular decorrelation, the greater the pursuit asymmetry: for 15 degrees /s
      target motion, the NBI in the 12-week and 24-week animals was 16x and 22x greater
      respectively, than that in the 3-week animals (ANOVA, P=0.03). CONCLUSIONS:
      Binocular decorrelation in primates during an early period of fusion development
      causes permanent smooth pursuit asymmetries when the duration exceeds the
      equivalent of 3 months in human. These findings support the conclusion that early
      correction of infantile strabismus promotes normal development of cerebral gaze
      pathways.

PMID- 18708130
TI  - Two different clades of copia-like retrotransposons in the red alga, Porphyra
      yezoensis.
AB  - A copia-like retrotransposon referred to as PyRE1G1 was isolated from the genome
      of the red alga Porphyra yezoensis. PyRE1G1 is 4807 bp in length, with 204 bp
      long terminal repeats (LTRs) at both ends. PyRE1G1 has an open reading frame of
      1401 residues encoding gag, protease, integrase, reverse transcriptase (RT), and
      RNase H. From the order of gene arrangement of proteins, PyRE1G1 appears to be a
      copia-like retrotransposon. Genomic Southern blot analysis suggests that PyRE1G1
      consists of a small gene family. From the phylogenetic tree of RT sequences,
      PyRE1G1 is grouped in the clade of usual copia elements and distinct from the
      previously isolated red algal copia-like gene PyRE10G in that the latter is
      closely related to a new clade of aquatic animal-specific copia-like
      retrotransposons.

PMID- 18708131
TI  - Use of long term dermal sensitization followed by intratracheal challenge method
      to identify low-dose chemical-induced respiratory allergic responses in mice.
AB  - The inhalation of many types of chemicals, including pesticides, perfumes, and
      other low-molecular weight chemicals, is a leading cause of allergic respiratory
      diseases. We attempted to develop a new test protocol to detect environmental
      chemical-related respiratory hypersensitivity at low and weakly immunogenic
      doses. We used long-term dermal sensitization followed by a low-dose
      intratracheal challenge to evaluate sensitization by the well-known respiratory
      sensitizers trimellitic anhydride (TMA) and toluene diisocyanate (TDI) and the
      contact sensitizer 2,4-dinitrochlorobenzene (DNCB). After topically sensitizing
      BALB/c mice (9 times in 3 weeks) and challenging them intratracheally with TMA,
      TDI, or DNCB, we assayed differential cell counts and chemokine levels in
      bronchoalveolar lavage fluid (BALF); lymphocyte counts, surface antigen
      expression of B cells, and local cytokine production in lung-associated lymph
      nodes (LNs); and antigen-specific IgE levels in serum and BALF. TMA induced
      marked increases in antigen-specific IgE levels in both serum and BALF,
      proliferation of eosinophils and chemokines (MCP-1, eotaxin, and MIP-1beta) in
      BALF, and proliferation of Th2 cytokines (interleukin (IL)-4, IL-10, and IL-13)
      in restimulated LN cells. TDI induced marked increases in levels of cytokines (IL
      4, IL-10, IL-13, and IFN-gamma) produced by restimulated LN cells. In contrast,
      DNCB treatment yielded, at most, small, nonsignificant increases in all
      parameters. Our protocol thus detected respiratory allergic responses to low
      molecular weight chemicals and may be useful for detecting environmental chemical
      related respiratory allergy.

PMID- 18708132
TI  - Cadmium exerts toxic effects on ovarian steroid hormone release in rats.
AB  - This study examined the toxic effects of cadmium on the function of sexual
      hormone release in the ovaries of rats and the mechanism of this dysregulation.
      In vivo, adult female rats were randomly assigned to four groups based on weight.
      Cadmium was given ip 5 days/week for 6 weeks at doses of 1.0, 0.5, 0.25 and
      0mg/kg. Following euthanasia, the ovaries were removed and placed into culture
      medium for 3h. The levels of progesterone (P) and estadiol (E) in the culture
      medium were then measured by radioimmunoassay. In vitro studies were done using
      the ovaries of adult rats in different stages of estrous (proestrus, estrus,
      metestrus and diestrus). Individual ovaries were collected, placed into culture
      medium and exposed to 0, 0.1, 1, or 2mM of CdCl(2) for 3h, at which time the
      levels of P and E in the ovary culture serum were determined by radioimmunoassay.
      The in vivo results showed that the levels of P and E in the ovary culture serum
      (5.3+/-1.4 ng/ml and 1.4+/-0.4 pg/ml, respectively) decreased significantly in
      the high dose group compared to the control (9.2+/-0.9 ng/ml and 3.9+/-0.7 pg/ml,
      respectively). In vitro, there were significant differences in P and E in between
      the different concentrations of cadmium and also between the different stages of
      the estrous cycle. These data suggest that cadmium can inhibit P and E release in
      ovaries. This may represent an important mechanism of endocrine disruption.

PMID- 18708133
TI  - Non-linear pharmacodynamics in the transfection efficiency of a non-viral gene
      delivery system.
AB  - Transfection efficiencies using LipofectAMINE varied by more than three orders of
      magnitude depending on the concentrations of lipid and plasmid DNA (pDNA) used to
      prepare the lipoplexes. When lipoplexes were formed at lower concentrations a
      striking positive but non-linear relationship was found between dose and
      transfection efficiency, while at higher (i.e., normally used) concentrations a
      linear relationship was maintained. To determine the contribution of
      intracellular pharmacokinetics (PK) and pharmacodynamics (PD) to the observed
      nonlinearity, we quantified pDNA in whole cells and nuclei by real-time PCR and
      compared the results with the transfection efficiencies. There was no significant
      difference in the efficiency of intracellular PK; however, a remarkable
      difference was observed in the efficiency of PD. Analysis of individual cells by
      confocal laser scanning microscopy (CLSM) revealed that the amount of nuclear
      delivered pDNA was higher for lipoplexes prepared at the normal concentration
      (NCL) compared to those of lipoplexes prepared at low concentration (LCL).
      Moreover, the size of the NCL was larger than that of the LCL. Both the size of
      the lipoplex particle and the dose appear to contribute to the non-linear
      efficiency of PD. These results emphasize the need to control not only
      intracellular PK, but also PD for the rational development of non-viral gene
      delivery systems.

PMID- 18708134
TI  - Analgesic and anti-arthritic effects of Lingzhi and San Miao San supplementation
      in a rat model of arthritis induced by Freund's complete adjuvant.
AB  - AIM OF STUDY: In this study, we have investigated the analgesic and anti
      arthritic effects of a traditional Chinese medicine (TCM) combination of Lingzhi
      and San Miao San (SMS) in a rat model of arthritis induced by Freund's complete
      adjuvant (FCA). MATERIALS AND METHODS: Sprague-Dawley rats were induced with
      monoarthritis by single unilateral injection of FCA into the knee joint. The TCM
      combination was administered to the rats daily by intraperitoneal injection
      (50mg/(kgday)) or via oral administration (500mg/(kgday)) for 7 days before
      induction of arthritis and 7 days after. Extension angle that provoked struggling
      behavior, and size and blood flow of the rat knees were measured to give indexes
      of allodynia, edema, and hyperemia, respectively. The extent of cell
      infiltration, tissue proliferation, and erosions of joint cartilage provided
      additional indexes of the arthritis condition. RESULTS: FCA injection produced
      significant allodynia, edema, hyperemia, immune cell infiltration, synovial
      tissue proliferation, and erosions of joint cartilage in the ipsilateral knees
      compared with the contralateral saline-injected knees. Intraperitoneal injection
      of the TCM combination (50mg/(kgday)) suppressed allodynia, edema, and hyperemia
      in the inflamed knees, and oral administration (500mg/(kgday)) suppressed edema
      and hyperemia. Histological examination showed that the TCM administered by
      either route reduced immune cell infiltration and erosion of joint cartilage.
      CONCLUSIONS: These findings suggest the Lingzhi and SMS formulation has analgesic
      and anti-inflammatory effects in arthritic rat knees, and concur to previous
      clinical studies that showed the TCM combination reduced pain in rheumatoid
      arthritis patients, and extends its possible benefit to suppression of
      inflammatory symptoms in these patients.

PMID- 18708135
TI  - Don't stress out your immune system - just relax.

PMID- 18708136
TI  - Listeria monocytogenes infection in pregnant guinea pigs is associated with
      maternal liver necrosis, a decrease in maternal serum TNF-alpha concentrations,
      and an increase in placental apoptosis.
AB  - Stillbirths and spontaneous abortions can result when pregnant women are exposed
      to the food borne pathogen, Listeria monocytogenes. Fetuses and neonates account
      for one-third of the 2500 cases annually. The objectives were to determine the
      dose dependent trends of immunological and pathological effects in pregnant
      guinea pigs after infection with L. monocytogenes. Timed pregnant guinea pigs
      were treated on gestation day (gd) 35 with doses of 10(4) to 10(8) colony forming
      units (CFUs) and sacrificed on gd 56. Hepatic lesions were found in dams treated
      with >or=10(5)CFUs. Apoptosis was detected in significantly more placentas from
      dams treated with >or=10(6)CFUs compared to controls. Maternal serum TNF-alpha
      concentrations were significantly decreased in all dose groups compared to
      controls. In conclusion, increases in premature delivery, maternal hepatic
      effects and placental apoptosis along with a decrease in TNF-alpha concentrations
      were associated with L. monocytogenes infection in pregnant guinea pigs.

PMID- 18708137
TI  - DNA damage-induced reactive oxygen species (ROS) stress response in Saccharomyces
      cerevisiae.
AB  - Cells are exposed to both endogenous and exogenous sources of reactive oxygen
      species (ROS). At high levels, ROS can lead to impaired physiological function
      through cellular damage of DNA, proteins, lipids, and other macromolecules, which
      can lead to certain human pathologies including cancers, neurodegenerative
      disorders, and cardiovascular disease, as well as aging. We have employed
      Saccharomyces cerevisiae as a model system to examine the levels and types of ROS
      that are produced in response to DNA damage in isogenic strains with different
      DNA repair capacities. We find that when DNA damage is introduced into cells from
      exogenous or endogenous sources there is an increase in the amount of
      intracellular ROS which is not directly related to cell death. We have examined
      the spectrum of ROS in order to elucidate its role in the cellular response to
      DNA damage. As an independent verification of the DNA damage-induced ROS
      response, we show that a major activator of the oxidative stress response, Yap1,
      relocalizes to the nucleus following exposure to the DNA-alkylating agent methyl
      methanesulfonate. Our results indicate that the DNA damage-induced increase in
      intracellular ROS levels is a generalized stress response that is likely to
      function in various signaling pathways.

PMID- 18708138
TI  - The reaction of hydrogen peroxide with hemoglobin induces extensive alpha-globin
      crosslinking and impairs the interaction of hemoglobin with endogenous scavenger
      pathways.
AB  - Cell-free hemoglobin (Hb) enhances the oxidation-related toxicity associated with
      inflammation, ischemia, and hemolytic disorders. Hb is highly vulnerable to
      oxidative damage, and irreversible structural changes involving iron/heme
      oxidation, heme-adduct products, and amino acid oxidation have been reported.
      Specific structural features of Hb, such as unconstrained alpha-chains and
      molecular size, determine the efficiency of interactions between the endogenous
      Hb scavengers haptoglobin (Hp) and CD163. Using HPLC, mass spectrometry, and
      Western blotting, we show that H(2)O(2)-mediated Hb oxidation results in the
      formation of covalently stabilized globin multimers, with prominent
      intramolecular crosslinking between alpha-globin chains. These structural
      alterations are associated with reduced Hp binding, reduced CD163 interaction,
      and severely impaired endocytosis of oxidized Hb by the Hp-CD163 pathway. As a
      result, when exposed to oxidized Hb, CD163-positive HEK293 cells and human
      macrophages do not increase hemeoxygenase-1 (HO-1) expression, the physiological
      anti-oxidative macrophage response to Hb exposure. Failed Hb clearance,
      inadequate HO-1 expression, and the subsequent accumulation of oxidatively
      damaged Hb species might thus contribute to pathologies related to oxidative
      stress.

PMID- 18708139
TI  - Phylogenetic comparison of the known Chlamydia trachomatis sigma(66) promoters
      across to Chlamydia pneumoniae and Chlamydia caviae identifies seven poorly
      conserved promoters.
AB  - We used four different phylogenetic footprinting programs and the six chlamydial
      species with publicly available whole genome sequences to analyze the 12 known
      sigma(66) promoters of Chlamydia trachomatis that phylogenetically footprinted
      negative in our previous paper. The analysis showed that 7 of the 12 promoters
      were poorly conserved across C. trachomatis, Chlamydia pneumoniae and Chlamydia
      caviae. Interestingly, the associated gene sets for these seven promoters were
      homologs and the gene orders were well conserved across these three species.
      Additional phylogenetic footprinting, across different subsets from that used
      above, of the six publicly available whole chlamydial genome sequences and
      transcription initiation site mapping of chlamydial promoters was also performed.
      This analysis showed that two of the seven poorly conserved promoters, the
      promoters in the upstream regions of C. caviae ltuA and ltuB, were like
      Escherichia coli sigma(70) promoters. Therefore, these promoters are similar to
      the promoters of C. trachomatis ltuA and ltuB, as they are sigma(70)-like. Given
      the fact that 7 out of the 22 known sigma(66) promoters in C. trachomatis are
      poorly conserved across C. trachomatis, C. pneumoniae and C. caviae, we would
      like to suggest that many other chlamydial promoters are poorly conserved across
      these species.

PMID- 18708140
TI  - Reinforcement learning: the good, the bad and the ugly.
AB  - Reinforcement learning provides both qualitative and quantitative frameworks for
      understanding and modeling adaptive decision-making in the face of rewards and
      punishments. Here we review the latest dispatches from the forefront of this
      field, and map out some of the territories where lie monsters.

PMID- 18708142
TI  - Cortico-striatal representation of time in animals and humans.
AB  - Interval timing in the seconds-to-minutes range is crucial to learning, memory,
      and decision-making. Recent findings argue for the involvement of cortico
      striatal circuits that are optimized by the dopaminergic modulation of
      oscillatory activity and lateral connectivity at the level of cortico-striatal
      inputs. Striatal medium spiny neurons are proposed to detect the coincident
      activity of specific beat patterns of cortical oscillations, thereby permitting
      the discrimination of supra-second durations based upon the reoccurring patterns
      of subsecond neural firing. This proposal for the cortico-striatal representation
      of time is consistent with the observed psychophysical properties of interval
      timing (e.g. linear time scale and scalar variance) as well as much of the
      available pharmacological, lesion, patient, electrophysiological, and
      neuroimaging data from animals and humans (e.g. dopamine-related timing deficits
      in Huntington's and Parkinson's disease as well as related animal models). The
      conclusion is that although the striatum serves as a 'core timer', it is part of
      a distributed timing system involving the coordination of large-scale oscillatory
      networks.

PMID- 18708141
TI  - The 'when' parietal pathway explored by lesion studies.
AB  - The perception of events in space and time is at the root of our interactions
      with the environment. The precision with which we perceive visual events in time
      enables us to act upon objects with great accuracy and the loss of such functions
      due to brain lesions can be catastrophic. We outline a visual timing mechanism
      that deals with the trajectory of an object's existence across time, a crucial
      function when keeping track of multiple objects that temporally overlap or occur
      sequentially. Recent evidence suggests these functions are served by an extended
      network of areas, which we call the 'when' pathway. Here we show that the when
      pathway is distinct from and interacts with the well-established 'where' and
      'what' pathways.

PMID- 18708143
TI  - TOR signaling is required for amino acid stimulation of early trypsin protein
      synthesis in the midgut of Aedes aegypti mosquitoes.
AB  - Blood meal digestion in mosquitoes occurs in two phases, an early phase that is
      translationally regulated, and a late phase that is transcriptionally regulated.
      Early trypsin is a well-characterized serine endoprotease that is representative
      of other early phase proteases in the midgut that are only synthesized after
      feeding. Since the kinase Target of Rapamycin (TOR) has been implicated as a
      nutrient sensor in other systems, including the mosquito fat body, we tested if
      TOR signaling is involved in early trypsin protein synthesis in the mosquito
      midgut in response to feeding. We found that ingestion of an amino acid meal by
      female mosquitoes induces early trypsin protein synthesis, coincident with
      phosphorylation of two known TOR target proteins, p70S6 kinase (S6K) and the
      translational repressor 4E-Binding Protein (4E-BP). Moreover, in vitro culturing
      of midguts from unfed mosquitoes led to amino acid-dependent phosphorylation of
      S6K and 4E-BP which could be blocked by treatment with rapamycin, a TOR-specific
      inhibitor. Lastly, by injecting mosquitoes with TOR double stranded RNA (dsRNA)
      or rapamycin, we demonstrated that TOR signaling was required in vivo for both
      phosphorylation of S6K and 4E-BP in the midgut, and for translation of early
      trypsin mRNA in response to amino acid feeding. It may be possible to target the
      TOR signaling pathway in the midgut to inhibit blood meal digestion, and thereby,
      decrease fecundity and the spread of mosquito borne diseases.

PMID- 18708144
TI  - Gender differences in the treatment of HIV infection.
AB  - In recent years, following the successful development of highly active
      antiretroviral therapy (HAART), several studies have evaluated potential
      differences between men and women in the course of HIV infection, response to
      treatment, and drug pharmacokinetics. A slightly lower HIV viral load in
      untreated women has been reported, particularly at higher CD4+ levels, but this
      difference does not translate into gender-specific recommendations concerning
      initiation of therapy. Data on drug response suggest similar response of
      treatment and similar outcomes in men and women, but female subjects appear to be
      more susceptible to adverse events related to antiretroviral treatment. Social
      and behavioural factors may determine gender differences in therapeutic adherence
      and treatment discontinuation. The available evidence on pharmacokinetics of
      antiretroviral drugs suggests higher exposure in women compared to men. The
      factors and mechanisms more likely to be clinically relevant in determining this
      difference are represented by body weight and composition, renal clearance, and P
      glycoprotein activity. Many antiretroviral drugs influence P450 activity, and
      interactions are common. The results of the studies exploring gender differences
      in pharmacokinetics of anti-HIV drugs are often not consistent, but several
      mechanisms may be involved in determining a final difference, and it might be
      difficult to adjust for all potential confounders. Specific considerations are
      needed in the selection of anti-HIV regimens in pregnancy, which must ensure
      protection from both HIV transmission and adverse neonatal outcomes. In order to
      optimize treatment in all infected people with HIV, there is the need to conduct
      further research on gender differences in HIV therapeutics. To obtain this goal,
      specific studies should be designed and females' participation in both cohort
      studies and clinical trials should be promoted.

PMID- 18708145
TI  - Correlation of T-channel coding gene expression, IT, and the low threshold Ca2+
      spike in the thalamus of a rat model of absence epilepsy.
AB  - T-type Ca(2+) current-dependent burst firing of thalamic neurons is thought to be
      involved in the hyper-synchronous activity observed during absence seizures. Here
      we investigate the correlation between the expression of T-channel coding genes
      (alpha1G, -H, -I), T-type Ca(2+) current, and the T-current-dependent low
      threshold Ca(2+) spike in three functionally distinct thalamic nuclei (lateral
      geniculate nucleus; centrolateral nucleus; reticular nucleus) in a rat model of
      absence epilepsy, the WAG/Rij rats, and a non-epileptic control strain, the ACI
      rats. The lateral geniculate nucleus and centrolateral nucleus were found to
      primarily express alpha1G and alpha1I, while the reticular thalamic nucleus
      expressed alpha1H and alpha1I. Expression was higher in WAG/Rij when compared to
      ACI. The T-type Ca(2+) current properties matched the predictions derived from
      the expression pattern analysis. Current density was larger in all nuclei of
      WAG/Rij rats when compared to ACI and correlated with LTS size and the minimum
      LTS generating slope, while T-type Ca(2+) current voltage dependency correlated
      with the LTS onset potential.

PMID- 18708147
TI  - Recombinant human SMOCs produced by in vitro refolding: calcium-binding
      properties and interactions with serum proteins.
AB  - Secreted modular calcium-binding (SMOC) proteins are little known members of the
      BM-40 family of matricellular proteins. SMOC-1 is localized in basement
      membranes, while SMOC-2 exhibits pro-angiogenic properties and stimulates cell
      cycle progression via integrin-linked kinase. In this work we have expressed
      recombinant human SMOCs in inclusion bodies in Escherichia coli. Soluble proteins
      were prepared by in vitro refolding with a final yield of approximately 3mg of
      purified SMOCs per liter of bacterial culture. The folding state of the products
      and their ability to reversibly bind calcium ions were verified by CD
      spectroscopy. The EF hands of the refolded SMOCs were both functional, one had
      high affinity for calcium ions (K(d) values in the 0.7-1 microM range), while the
      other had lower affinity (K(d) values 20-25 microM). The proteins were also
      examined for their ability to bind blood serum proteins. Three of the bands
      specifically retained on SMOC-Sepharose were identified as C-reactive protein, an
      acute phase protein from the pentraxin family, the basement membrane and elastic
      fiber-associated fibulin-1, and vitronectin, which is involved in cell adhesion,
      migration and proliferation and binds numerous extracellular and membrane
      proteins, including integrins. The interactions were additionally confirmed in
      solution using purified individual proteins by the method of biotin label
      transfer from one interacting partner to the other. Their identification is among
      the first pieces of information about the action of the SMOCs on molecular level
      and opens new possibilities for future research aimed towards elucidating the
      physiological roles of these versatile proteins.

PMID- 18708146
TI  - Deletion of lysophosphatidic acid receptor LPA1 reduces neurogenesis in the mouse
      dentate gyrus.
AB  - Neurogenesis persists in certain regions of the adult brain including the
      subgranular zone of the hippocampal dentate gyrus wherein its regulation is
      essential, particularly in relation to learning, stress and modulation of mood.
      Lysophosphatidic acid (LPA) is an extracellular signaling phospholipid with
      important neural regulatory properties mediated by specific G protein-coupled
      receptors, LPA(1-5). LPA(1) is highly expressed in the developing neurogenic
      ventricular zone wherein it is required for normal embryonic neurogenesis, and,
      by extension may play a role in adult neurogenesis as well. By means of the
      analyses of a variant of the original LPA(1)-null mutant mouse, termed the Malaga
      variant or "maLPA(1)-null," which has recently been reported to have defective
      neurogenesis within the embryonic cerebral cortex, we report here a role for
      LPA(1) in adult hippocampal neurogenesis. Proliferation, differentiation and
      survival of newly formed neurons are defective in the absence of LPA(1) under
      normal conditions and following exposure to enriched environment and voluntary
      exercise. Furthermore, analysis of trophic factors in maLPA(1)-null mice
      demonstrated alterations in brain-derived neurotrophic factor and insulin growth
      factor 1 levels after enrichment and exercise. Morphological analyses of
      doublecortin positive cells revealed the anomalous prevalence of bipolar cells in
      the subgranular zone, supporting the operation of LPA(1) signaling pathways in
      normal proliferation, maturation and differentiation of neuronal precursors.

PMID- 18708148
TI  - Fast uptake and long-lasting binding of methamphetamine in the human brain:
      comparison with cocaine.
AB  - Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It
      produces large elevations in extracellular dopamine in the striatum through
      vesicular release and inhibition of the dopamine transporter. In the U.S. abuse
      prevalence varies by ethnicity with very low abuse among African Americans
      relative to Caucasians, differentiating it from cocaine where abuse rates are
      similar for the two groups. Here we report the first comparison of
      methamphetamine and cocaine pharmacokinetics in brain between Caucasians and
      African Americans along with the measurement of dopamine transporter availability
      in striatum. Methamphetamine's uptake in brain was fast (peak uptake at 9 min)
      with accumulation in cortical and subcortical brain regions and in white matter.
      Its clearance from brain was slow (except for white matter which did not clear
      over the 90 min) and there was no difference in pharmacokinetics between
      Caucasians and African Americans. In contrast cocaine's brain uptake and
      clearance were both fast, distribution was predominantly in striatum and uptake
      was higher in African Americans. Among individuals, those with the highest
      striatal (but not cerebellar) methamphetamine accumulation also had the highest
      dopamine transporter availability suggesting a relationship between METH exposure
      and DAT availability. Methamphetamine's fast brain uptake is consistent with its
      highly reinforcing effects, its slow clearance with its long-lasting behavioral
      effects and its widespread distribution with its neurotoxic effects that affect
      not only striatal but also cortical and white matter regions. The absence of
      significant differences between Caucasians and African Americans suggests that
      variables other than methamphetamine pharmacokinetics and bioavailability account
      for the lower abuse prevalence in African Americans.

PMID- 18708149
TI  - Developmental changes in neural activation and psychophysiological interaction
      patterns of brain regions associated with interference control and time
      perception.
AB  - Interference control and time perception are mediated by common neural networks,
      including the frontal and parietal lobes, the cerebellum and the basal ganglia.
      Previous studies have shown that while time perception develops early in life,
      interference control seems to follow a protracted course of maturation into late
      adolescence. Thus, the current study examined developmental changes in neural
      activation and functional interaction between brain regions during a combined
      time discrimination and interference control task using fMRI. Thirty-four
      participants, aged 8-15 years, were scanned while performing a spatial stimulus
      response compatibility (SRC) task and a time discrimination (TD) task using
      identical stimuli. We found shared neural activation in a fronto-parieto
      cerebellar network as well as task-specific patterns of psychophysiological
      interaction with positive coupling between the right inferior frontal gyrus
      (IFG), the superior parietal lobes bilaterally, the contralateral IFG and the
      thalamus during interference control and positive interactions between the right
      IFG and bilateral cerebellar activity and the thalamus during time
      discrimination. Developmental changes in task performance and brain activation
      patterns were only observed during the SRC task, with increased neural activity
      in the left inferior parietal gyrus and positive coupling between fronto-parietal
      brain regions that was only observed in the adolescents group. These results
      suggest that although both cognitive tasks rely on a shared neural network,
      distinct developmental curves of brain activation and connectivity could be
      observed associated with differential maturation patterns underlying cognitive
      development.

PMID- 18708150
TI  - Reduction of chlortetracycline-resistant Escherichia coli in weaned piglets fed
      fermented liquid feed.
AB  - We investigated the change in chlortetracycline resistance in 360 Escherichia
      coli strains separated from the feces of piglets fed fermented liquid feed (FLF)
      in comparison with those fed dry feed (control). The total amount of lactic acid
      bacteria in feces was 8.77 x 10(8) CFU/g DM at weaning, which increased to 1.23 x
      10(12) CFU/g DM (FLF) at 28 days after weaning (P<0.001). As a result of the
      antibiotic susceptibility test, almost all isolates were chlortetracycline
      resistant (CTCR) until 14 days after weaning both in the FLF and control groups.
      At 28 days, the CTCR E. coli decreased to 22.2% in the FLF group, while the
      proportion of resistant bacteria was 88.9% in the control group. In addition, as
      a result of the gene analysis, it was clarified that there is a relation between
      the decrease in the minimum inhibitory concentration values and the possession
      rate of the tetracycline-resistance gene tet(A), tet(B) and tet(D). These results
      show that FLF caused an increase in the number of lactic acid bacteria in the
      intestines, and suggested that the feeding of FLF can possibly reduce antibiotic
      resistance bacteria.

PMID- 18708151
TI  - A miRacle in plant development: role of microRNAs in cell differentiation and
      patterning.
AB  - MicroRNAs (miRNAs) are endogenous small regulatory RNAs, which control gene
      expression in eukaryotes. In plants they repress mRNA targets containing a highly
      complementary site, either by cleavage or translational repression. Studies of
      individual miRNA/target interactions highlight the involvement of the miRNA-based
      regulations in a broad range of developmental programs, throughout plant
      lifecycle. MicroRNAs can have distinct regulatory functions on their targets:
      some determine their spatial accumulation, some have a buffering role that
      ensures the robustness of their expression pattern, and finally others establish
      the temporal expression of targeted genes.

PMID- 18708152
TI  - The impact of chromatin regulation on the floral transition.
AB  - Transcription in eukaryotes is regulated by many enzymes that influence the
      nuclear organization of DNA in chromatin. Several of these enzymes regulate
      histone modifications. These modifications function as a platform for assembly of
      protein complexes that influence chromatin structure. Dynamic changes between
      chromatin states that facilitate or inhibit transcription are important in the
      transcriptional regulation of pathways controlling floral induction in response
      to environmental and developmental signals. This review focuses on the
      mechanistic aspects of histone modifications and chromatin changes at flowering
      time genes and how these relate to the initiation of flowering.

PMID- 18708153
TI  - Chromatin, photoperiod and the Arabidopsis circadian clock: a question of time.
AB  - Plants, as many other organisms, synchronize the timing of their physiology and
      development by using an endogenous mechanism called circadian clock. Perception
      of environmental changes during the day-night cycle is crucial for circadian
      function, which relies on transcriptional feedback loops at the core of a central
      oscillator. Recent studies in Arabidopsis have shown that the transcriptional
      regulation of clock gene expression is governed by rhythmic changes in chromatin
      structure. The chromatin remodelling activities relevant for clock function are
      modulated by day-length or photoperiod, suggesting a mechanism by which the plant
      clock synchronizes development with the external time. Evidence that a central
      component of the mammalian clock has histone acetyltransferase activity suggests
      that chromatin remodelling has evolved as an important mechanism for circadian
      function.

PMID- 18708156
TI  - Epigenetic memory transmission through mitosis and meiosis in plants.
AB  - Gene activities can be regulated by epigenetic modifications of nucleotides and
      chromatin that are stably propagated through somatic cell divisions and, in some
      cases, across generations. The mechanisms that control epigenetic marks have
      recently been uncovered using model organisms, such as the flowering plant
      Arabidopsis thaliana. In Arabidopsis, perturbation of epigenetic gene activity
      often results in heritable developmental phenotypes. Stable, but potentially
      reversible, changes in epigenetic status can also be sources for phenotypic
      variations in natural plant populations.

PMID- 18708154
TI  - SOCS regulation of the JAK/STAT signalling pathway.
AB  - The suppressor of cytokine signalling (SOCS) proteins were, as their name
      suggests, first described as inhibitors of cytokine signalling. While their
      actions clearly now extend to other intracellular pathways, they remain key
      negative regulators of cytokine and growth factor signalling. In this review we
      focus on the mechanics of SOCS action and the complexities of the mouse models
      that have underpinned our current understanding of SOCS biology.

PMID- 18708157
TI  - Cobalt induces oxidative stress in isolated liver mitochondria responsible for
      permeability transition and intrinsic apoptosis in hepatocyte primary cultures.
AB  - It is well established that cobalt mediates the occurrence of oxidative stress
      which contributes to cell toxicity and death. However, the mechanisms of these
      effects are not fully understood. This investigation aimed at establishing if
      cobalt acts as an inducer of mitochondrial-mediated apoptosis and at clarifying
      the mechanism of this process. Cobalt, in the ionized species Co(2+), is able to
      induce the phenomenon of mitochondrial permeability transition (MPT) in rat liver
      mitochondria (RLM) with the opening of the transition pore. In fact, Co(2+)
      induces mitochondrial swelling, which is prevented by cyclosporin A and other
      typical MPT inhibitors such as Ca(2+) transport inhibitors and bongkrekic acid,
      as well as anti-oxidant agents. In parallel with mitochondrial swelling, Co(2+)
      also induces the collapse of electrical membrane potential. However in this case,
      cyclosporine A and the other MPT inhibitors (except ruthenium red and EGTA) only
      partially prevent DeltaPsi drop, suggesting that Co(2+) also has a proton leakage
      effect on the inner mitochondrial membrane. MPT induction is due to oxidative
      stress, as a result of generation by Co(2+) of the highly damaging hydroxyl
      radical, with the oxidation of sulfhydryl groups, glutathione and pyridine
      nucleotides. Co(2+) also induces the release of the pro-apoptotic factors,
      cytochrome c and AIF. Incubation of rat hepatocyte primary cultures with Co(2+)
      results in apoptosis induction with caspase activation and increased level of
      expression of HIF-1alpha. All these observations allow us to state that, in the
      presence of calcium, Co(2+) is an inducer of apoptosis triggered by mitochondrial
      oxidative stress.

PMID- 18708155
TI  - New insights into the roles of Stat5a/b and Stat3 in T cell development and
      differentiation.
AB  - T cell development and differentiation is carefully orchestrated by a series of
      cytokines. The importance of STAT family proteins in mediating signals by these
      cytokines is well-known, but new information on the role of STATs in novel
      aspects of T cell function and T cell subsets continues to accumulate. Recent
      studies have placed Stat5a/b and Stat3 center stage in T cell development and
      differentiation. Stat5a/b are indispensable in T regulatory (Treg) cell
      development and maintenance, and negatively regulate T helper 17 (Th17) cell
      differentiation. Conversely, Stat3 is essential for Th17 differentiation and
      inhibits Treg cells. The balance of Treg and Th17 cells is thought to be critical
      in maintaining immune tolerance, while preserving effective host defense.
      Therefore, Stat5a/b and Stat3 are emerging to be key players in T cell
      differentiation and homeostasis.

PMID- 18708159
TI  - Lipid droplet-organelle interactions; sharing the fats.
AB  - Lipid droplets (LDs) are key cellular organelles involved in lipid storage and
      mobilisation. While the major signalling cascades and many of the regulators of
      lipolysis have been identified, the cellular interactions involved in lipid
      mobilisation and release remain largely undefined. In non-adipocytes, LDs are
      small, mobile and interact with other cellular compartments. In contrast,
      adipocytes primarily contain very large, immotile LDs. The striking morphological
      differences between LDs in adipocytes and non-adipocytes suggest that key
      differences must exist in the manner in which LDs in different cell types
      interact with other organelles. Recent studies have highlighted the complexity of
      LD interactions, which can be both homotypic, with each other, and heterotypic,
      with other organelles. The molecules involved in these interactions are also now
      emerging, including Rab proteins, key regulators of membrane traffic, and
      caveolin, an integral membrane protein providing a functional link between the
      cell surface and LDs. Here we summarise recent insights into the cell biology of
      the LD particularly focussing on the homotypic and heterotypic interactions in
      both adipocytes and non-adipocytes. We speculate that these interactions may
      involve inter-organelle membrane contact sites or a hemi-fusion type mechanism to
      facilitate lipid transfer.

PMID- 18708158
TI  - Apoptosis of metastatic prostate cancer cells by a combination of cyclin
      dependent kinase and AKT inhibitors.
AB  - Effective treatments for advanced prostate cancer are much needed. Toward this
      goal, we show apoptosis and impaired long-term survival of androgen-independent
      prostate cancer cells (PC3 and PC3 derivatives) co-treated with the cyclin
      dependent kinase (CDK) inhibitor roscovitine and an AKT inhibitor (LY294002 or
      API-2). Apoptosis of PC3 cells by the drug combination required caspase-9 but not
      caspase-8 activity and thus is mitochondria-dependent. Roscovitine reduced
      amounts of the caspase inhibitor XIAP, and API-2 increased amounts of the BH3
      only protein Bim. PC3 cells apoptosed when co-treated with API-2 and either cdk9
      siRNA, dominant-negative cdk9, or the cdk9 inhibitor DRB; they did not apoptose
      when co-treated with API-2 and XIAP siRNA. Bax accumulated in mitochondria in
      response to API-2, whereas release of cytochrome c from mitochondria required
      both API-2 and roscovitine. We suggest that roscovitine elicits events that
      activate Bax once it translocates to mitochondria and that inactivation of cdk9
      signals these events and the down-regulation of XIAP. Collectively, our data show
      apoptosis of prostate cancer cells by a drug combination and identify Bax
      activation as a basis of cooperation.

PMID- 18708160
TI  - Xenobiotic metabolism markers in marine fish with different trophic strategies
      and their relationship to ecological variables.
AB  - Nine fish species of commercial interest from six teleost families and two
      species of elasmobranchs were selected for characterisation of hepatic biomarkers
      used in early-warning assessment of pollutant exposure. The sampling was carried
      out in front of the Barcelona coast (NW Mediterranean) during December 2006 at
      shelf (53 m) and slope (660 m) depths. The enzymes considered included the
      antioxidant defence catalase (CAT) and glutathione reductase (GR), phase I
      ethoxyresorufin O-deethylase (EROD) and phase II glutathione S-transferase (GST).
      Protein yield (PY) was used as a general marker of hepatic protein synthesis.
      Significant interspecies differences were evidenced, although each marker varied
      independently. Enzymatic activities in teleosts were higher than in
      elasmobranchs; they were very low in Scyliorhinus canicula (mainly a benthic
      feeder), but not so low in Galeus melastomus (pelagic feeder). In relation to
      depth, shallow water, shelf-living species had higher metabolic activities.
      Trophic variables were significantly related to PY and EROD activity, and were
      especially high in benthic/suprabenthic feeders. Trophic level (deduced from
      stable isotopy) and stomach fullness were associated with all hepatic markers,
      except GR. Swimming capacity was related to all hepatic enzymes. Our findings can
      be applied, not only from the perspective of conservation ecology regarding
      pollution, but also in fisheries, due to the economic interest of the species
      involved.

PMID- 18708161
TI  - Evolution and dispersal of St. Louis encephalitis virus in the Americas.
AB  - Using a Bayesian coalescent approach on a dataset of 73 envelope gene sequences
      we estimated substitution rates and dates of divergence for St. Louis
      encephalitis virus (SLEV) in the Americas. We found significant rate
      heterogeneity among lineages, such that "relaxed" molecular clock models were
      much better supported than a strict molecular clock. The mean substitution rate
      estimated for all SLEV was 4.1x10(-4)substitutions/site/year (95% HPD 2.5-5.7)
      higher than previous estimates that relied on the less well-suited strict clock.
      Mean substitution rates for individual lineages varied from 3.7x10(-4) to 7.2x10(
      4)substitutions/site/year. For the first time we also assessed the magnitude and
      direction of viral gene flow within the Americas. The overall direction of gene
      flow during the period represented by the phylogeny is from South to North, and
      the region between 15 degrees N and 30 degrees N latitude appears to be the major
      source of virus for the rest of North America, which is consistent with migratory
      birds returning to their northern breeding grounds having acquired infection
      while wintering in the region of the Gulf of Mexico.

PMID- 18708162
TI  - Recovery of IFN-gamma levels in PBMCs from lepromatous leprosy patients through
      the synergistic actions of the cytokines IL-12 and IL-18.
AB  - The shift to the production of a Th1 cytokine profile during an intracellular
      infection has been shown to depend on antigen presenting cells-derived IL-12 and
      T-cell-derived IFN-gamma production. IL-18 facilitates Th1 priming in synergy
      with IL-12 through the stimulation of IFN-gamma production by T cells, B cells,
      NK cells, macrophages and DCs. A low level of IFN-gamma production in PBMC
      cultures from lepromatous leprosy patients (LL) has been previously reported by
      several groups. We evaluated the synthesis of this cytokine after exogenous
      addition of recombinant IL-12 and IL-18 (IL12/IL18) in order to induce recovery
      of the IFN-gamma levels with Mycobacterium leprae antigenic stimulation. The aim
      of this study was to investigate if exogenous addition of IL12/IL18 to PBMC cell
      cultures in the presence of M. leprae antigens could induce recovery of IFN-gamma
      levels. We found that IFN-gamma levels in PBMCs cultured from LL patients were
      reestablished after exogenous addition of exogenous IL12/IL18 and we also
      observed a diminished IL-18R expression. Although the molecular mechanisms of
      IL12/IL18 synergy have not been clearly elucidated, we assume that recombinant
      cytokines can activate several transcription factors that induce IFN-gamma
      synthesis.

PMID- 18708163
TI  - hMTH1 depletion promotes oxidative-stress-induced apoptosis through a Noxa- and
      caspase-3/7-mediated signaling pathway.
AB  - Although the accumulation of 8-oxo-dGTP in DNA is associated with apoptotic cell
      death and mutagenesis, little is known about the exact mechanism of hMTH1
      mediated suppression of oxidative-stress-induced cell death. Therefore, we
      investigated the regulation of DNA-damage-related apoptosis induced by oxidative
      stress using control and hMTH1 knockdown cells. Small interfering RNA (siRNA) was
      used to suppress hMTH1 expression in p53-proficient GM00637 and H460 cells,
      resulting in a significant increase in apoptotic cell death after H(2)O(2)
      exposure; however, p53-null, hMTH1-deficient H1299 cells did not exhibit H(2)O(2)
      induced apoptosis. In addition, hMTH1-deficient GM00637 and H460 cells showed
      increased caspase-3/7 activity, cleaved caspase-8, and Noxa expression, and gamma
      H2AX formation in response to H(2)O(2). In contrast, the caspase inhibitors, p53
      siRNA, and Noxa-siRNA suppressed H(2)O(2)-induced cell death. Moreover, in 8-week
      (long-term) cultured H460 and H1299 cells, hMTH1 suppression increased cell
      death, Noxa expression, and gamma-H2AX after H(2)O(2) exposure, compared to 3
      week (short-term) cultured cells. These data indicate that hMTH1 plays an
      important role in protecting cells against H(2)O(2)-induced apoptosis via a Noxa-
      and caspase-3/7-mediated signaling pathway, thus conferring a survival advantage
      through the inhibition of oxidative-stress-induced DNA damage.

PMID- 18708164
TI  - Spectrum of mutational events in the absence of DOG-1/FANCJ in Caenorhabditis
      elegans.
AB  - The Caenorhabditis elegans ortholog of the Fanconi anemia pathway component J
      (FANCJ) is DOG-1, which is essential for genome stability. Previous studies have
      shown that disruption of the dog-1 gene generates small deletions of poly-C/poly
      G tracts detectable by PCR and results in a mutator phenotype. In this paper, we
      describe the isolation and characterization of lethal mutations resulting from
      the loss of dog-1 function. The mutant strains were analyzed using a combination
      of techniques including genetic mapping, SNP mapping, and oaCGH (oligo array
      Comparative Genome Hybridization). Using the eT1 balancer system to recover
      lethal mutants, we isolated, in addition to small deletions, large chromosomal
      rearrangements, including duplications, translocations and deficiencies. The
      forward mutation frequency was 10-fold higher than the spontaneous frequency for
      eT1, and equivalent to that observed for low doses of standard mutagens. From a
      screen for suppressors of mdf-1/MAD1 lethality, we previously had isolated such
      4(h2168), shown here to be a large tandem duplication. Thus, the range of
      mutational events caused by lack of DOG-1/FANCJ is much broader than previously
      described.

PMID- 18708165
TI  - Recurrent pericarditis: infectious or autoimmune?
AB  - The etiology and pathogenesis of idiopathic recurrent acute pericarditis (IRAP)
      remain controversial standing like a bridge that crosses infectious, autoimmune
      and autoinflammatory pathways. Anything may cause acute pericarditis; Echo-virus,
      and Coxsackie are the most frequently involved viruses, Mycobacterium
      tuberculosis and Coxiella burnetii the most common bacteria, but in 85% of cases
      it remains "idiopathic". Recurrences occur in up to 20-50% of patients. An immuno
      mediated pathogenesis is suggested by the presence of pro-inflammatory cytokines
      in pericardial fluid, the presence of antinuclear autoantibodies (ANA) in sera of
      the patients, the occurrence of new autoimmune diagnoses and the good response to
      anti-inflammatory or immunosuppressive therapy. Nonsteroidal anti-inflammatory
      drugs (NSAIDs) must be used at recommended dosages, till the resolution of
      symptoms and normalization of C-reactive protein and erythrocyte sedimentation
      rate. Corticosteroids should be used rarely, at low doses, with an extremely low
      tapering and with osteoporosis prevention. Colchicine leads to a clinically
      important and statistically significant benefit, reducing recurrences by 50%. The
      long term outcome of IRAP is good, without evidence of constriction even after a
      very long follow-up.

PMID- 18708166
TI  - A new strategy for the early diagnosis of rheumatoid arthritis: a combined
      approach.
AB  - Rheumatoid arthritis [RA] is one of the most common and severe autoimmune
      rheumatic diseases, diagnosed primarily according to clinical manifestations and
      radiological reports. For many years, laboratory diagnosis of rheumatoid
      arthritis has relied on the detection of rheumatoid factor [RF], as established
      by the ACR criteria. A recent test to detect antibodies towards citrullinated
      peptides, called the anti-CCP assay, showed a similar sensitivity but a more
      elevated specificity than the RF test. Our intention was the recognition of an
      optimal diagnostic strategy that exhibits the highest sensitivity and specificity
      for RA detection. To this purpose, we examine the usefulness of autoantibodies in
      RA testing, evaluating the diagnostic performance of conventional and innovative
      assays for RF detection, and ELISA anti-CCP test, for anti-CCP antibodies
      detection, by a prospective study. Multiplex cytofluorimetric test appeared to be
      more sensitive and specific than nephelometric assay for RF detection. Hence, a
      novel combined approach, significantly increasing the diagnostic sensitivity for
      RA, was planned, employing the multiplex RF test in combination with the anti-CCP
      test.

PMID- 18708167
TI  - Predictivity and sensitivity of animal models of arthritis.
AB  - Arthritis literally means joint inflammation. Arthritis is not a single disease.
      Arthritis refers to a group of rheumatic diseases and other conditions that can
      cause pain, stiffness and swelling in the joints. The forms range from those
      related to wear and tear of cartilage (such as osteoarthritis) to those
      associated with inflammation resulting from an overactive immune system (such as
      rheumatoid arthritis). Arthritis is more heterogeneous and this is an important
      starting point when discussing animal models for arthritis. Animal models are
      instrumental in understanding the etiology and pathogenetic mechanisms of
      rheumatoid arthritis. Several new mouse models have either been produced. Various
      methods have been applied to induce in animals experimental models of arthritis
      which would provide important insights into the aetiopathogenetic mechanisms of
      human RA.

PMID- 18708168
TI  - The role of innate immunity in the induction of autoimmunity.
AB  - The autoimmune diseases are a diverse group of conditions characterized by
      abnormal B and T cell reactivity in association with autoantibody production.
      Among these diseases, systemic lupus erythematosus (SLE) is notable for the
      expression of antibodies to DNA, with these antibodies representing diagnostic
      markers. While mammalian DNA is immunologically inert, DNA from bacteria can
      potently stimulate the innate immune system, activating both toll-like receptors
      (TLRs) as well as non-TLR internal receptors. Since the sera of normal humans
      contain antibodies specific for bacterial DNA, this molecule appears to be
      immunogenic during infection. In pre-autoimmune mice, immunization with bacterial
      DNA can induce anti-DNA autoantibody production, suggesting a role in initiating
      this response. The immune properties of DNA are mutable, however, since mammalian
      DNA can acquire immunological activity when bound to certain proteins or anti-DNA
      antibodies to form immune complexes. In SLE, these immune complexes can drive the
      production of interferon by plasmacytoid dendritic cells, thereby intensifying
      autoimmunity. Together, these observations suggest that DNA can induce innate as
      well as adaptive immune responses and promote the pathogenesis of SLE because of
      its intrinsic immunostimulatory activity.

PMID- 18708169
TI  - Immunopathogenesis of HCV-related endocrine manifestations in chronic hepatitis
      and mixed cryoglobulinemia.
AB  - Hepatitis C Virus (HCV) is known to be responsible for both hepatic and
      extrahepatic diseases (HCV-related extrahepatic diseases = HCV-EHDs). The most
      important systemic HCV-EHDs are mixed cryoglobulinemia and lymphoproliferative
      disorders, while the most frequent and clinically important endocrine HCV-EHDs
      are thyroid disorders and type 2 diabetes mellitus (T2D). From a meta-analysis of
      the literature a significant association between HCV infection and thyroid
      autoimmunity and hypothyroidism has been reported. A high prevalence of thyroid
      cancer has been reported, too. Furthermore, several clinical epidemiologic
      studies have reported that HCV infection is associated to T2D. Many studies have
      linked Th1 immune response with HCV infection, thyroid autoimmunity, or diabetes.
      These findings suggest that a possible common immunological Th1 pattern could be
      the pathophysiological base of the association of HCV-EHDs, with thyroid
      autoimmunity and T2D. In fact, HCV infection of thyrocytes or beta-cells may act
      by upregulating CXCL10 secretion in these cells that is responsible for Th1
      lymphocyte recruitment. Th1 response leads to increased IFNgamma and TNFalpha
      production that in turn stimulates CXCL10 secretion by the target cells, thus
      perpetuating the immune cascade. This process may lead to the appearance of
      thyroid autoimmune disorders or T2D in genetically predisposed subjects.

PMID- 18708171
TI  - Cost of growth and maintenance in chicken embryos during normoxic or hypoxic
      conditions.
AB  - During a large portion of embryonic development oxygen consumption (V(O2)) is
      mainly needed for maintenance (including organ function) and for growth. In an
      attempt to evaluate their relative contribution, we followed the assumption that
      the former is proportional to embryo's weight (W) and the latter to growth rate
      (GR), as V(O2)=aW+bGR, a and b being the respective proportionality coefficients.
      Fertile chicken eggs were incubated at the normal temperature (38 degrees C) and
      at various low-temperature conditions, which invariably decreased GR. At a few
      days intervals over the embryonic ages E9-E18, the W and V(O2) of the embryos
      were measured and GR computed from the age-W relationship. These simultaneous
      sets of W (g), GR (g/day) and V(O2) (ml/day) were used to solve the equation; a
      averaged 14.7 ml O(2) g(-1) day(-1) and b averaged 41.1 ml O(2) g(-1). Hence,
      over the period of incubation studied, the cost of growing 1g of tissue averaged
      about 3 times the cost of maintaining it. These coefficients were not
      significantly different whether computed during normal growth at 38 degrees C or
      during incubation at low temperatures, indicating that cooling only decreased GR
      and the cost required by it. Embryos incubated in hypoxia (15% O(2)) had low
      V(O2) originated not only by the decreased GR but also by a drop in the cost of
      maintenance, especially in the youngest embryos.

PMID- 18708172
TI  - HIF-1 and ventilatory acclimatization to chronic hypoxia.
AB  - Ventilatory acclimatization to hypoxia (VAH) is a time-dependent increase in
      ventilation and ventilatory O2-sensitivity that involves plasticity in carotid
      body chemoreceptors and CNS respiratory centers. Hypoxia inducible factor-1alpha
      (HIF-1alpha) controls the expression of several genes that increase physiological
      O2 supply. Studies using transgenic mice show HIF-1alpha expression in the
      carotid bodies and CNS with chronic sustained and intermittent hypoxia is
      important for VAH. Other O2-sensitive transcription factors such as HIF-2alpha
      may be important for VAH by reducing metabolic O2 demands also. Specific gene
      targets of HIF-1alpha shown to be involved in VAH include erythropoietin,
      endothelin-1, neuronal nitric oxide synthase and tyrosine hydroxylase. Other HIF
      1alpha targets that may be involved in VAH include vascular endothelial growth
      factor, heme oxygenase 1 and cytoglobin. Interactions between these multiple
      pathways and feedback control of HIF-1alpha expression from some of the targets
      support a complex and powerful role for HIF-1alpha in neural plasticity of
      physiological control circuits with chronic hypoxia.

PMID- 18708170
TI  - Trophic factor expression in phrenic motor neurons.
AB  - The function of a motor neuron and the muscle fibers it innervates (i.e., a motor
      unit) determines neuromotor output. Unlike other skeletal muscles, respiratory
      muscles (e.g., the diaphragm, DIAm) must function from birth onwards in
      sustaining ventilation. DIAm motor units are capable of both ventilatory and non
      ventilatory behaviors, including expulsive behaviors important for airway
      clearance. There is significant diversity in motor unit properties across
      different types of motor units in the DIAm. The mechanisms underlying the
      development and maintenance of motor unit diversity in respiratory muscles
      (including the DIAm) are not well understood. Recent studies suggest that trophic
      factor influences contribute to this diversity. Remarkably little is known about
      the expression of trophic factors and their receptors in phrenic motor neurons.
      This review will focus on the contribution of trophic factors to the
      establishment and maintenance of motor unit diversity in the DIAm, during
      development and in response to injury or disease.

PMID- 18708173
TI  - PDX-1 interaction and regulation of the Pancreatic Derived Factor (PANDER, FAM3B)
      promoter.
AB  - Pancreatic Derived Factor (PANDER) is a novel cytokine-like protein dominantly
      expressed within the endocrine pancreas. Our previous study demonstrated that the
      PANDER promoter was both tissue-specific and glucose-responsive. Surrounding the
      PANDER transcriptional start site are several putative A- and E-Box elements that
      may bind to the various pancreatic transcriptional factors of MafA, BETA2/NeuroD,
      and Pancreatic Duodenal Homeobox-1 (PDX-1). To characterize the transcriptional
      regulatory factors involved in PANDER gene expression, we performed co
      transfection reporter gene analysis and demonstrated upregulation by all three
      transcription factors, with the greatest individual increase stemming from PDX-1.
      Potential binding of PDX-1 to A box (TAAT) regions of the PANDER promoter was
      demonstrated by chromatin immunoprecipitation (ChIP) and further corroborated by
      electrophoretic mobility shift assay (EMSA). Binding of PDX-1 to the A box
      regions was inhibited by mutagenized (TAGT) oligonucleotides. Site-directed
      mutagenesis of the three PDX-1 A box binding motifs revealed that A box sites 2
      and 3 in combination were critical for maximal gene expression and deletion
      resulted in a 82% reduction in promoter activity. Furthermore, deletion of A box
      sites 2 and 3 completely diminished the glucose-responsiveness of the PANDER
      promoter. Our findings demonstrate that PANDER is a potential PDX-1 target gene
      and the A box sites within the promoter region are critical for basal and glucose
      stimulated PANDER expression.

PMID- 18708174
TI  - Variations in the ratios of co-cultured mesenchymal stem cells and chondrocytes
      regulate the expression of cartilaginous and osseous phenotype in alginate
      constructs.
AB  - As mesenchymal stem cells (MSCs) are capable of self-renewal and multilineage
      differentiation, the feasibility and efficacy of co-culturing human MSCs (hMSCs)
      with rabbit articular chondrocytes (rACs) to promote chondrogenic and osteogenic
      differentiation of hMSCs for clinical osteoarthritic therapy were investigated in
      the present study. The two distinct cell types were encapsulated in alginate
      hydrogels singly or in one of three ratios (2:1, 1:1, 1:2 of hMSCs to rACs) and
      cultured under chondrogenic conditions for 28 days. The results demonstrated that
      newly synthesized cartilaginous extracellular matrix (ECM) and type II collagen
      (col-2) gene signal were upregulated with greater hMSC ratios and longer culture
      periods. However, a specific col-2 gene probe for human was found only in single
      hMSC group but absent in all co-culture groups, which indicate that the enhanced
      cartilaginous phenotype originated from the co-cultured rACs. Osseous phenotype
      was histologically detected only in the 2:1 group on day 28; and xenogenic
      osteocalcin assay showed that it originated from hMSCs. This suggests that
      variations in the ratios of co-cultured hMSC and rAC regulated the cartilaginous
      and osseous phenotype as well as the differentiation of hMSCs in alginate
      constructs. The study provides new insights into the role of cell-cell
      interactions in regulating both cell differentiation and cell function and
      highlights the importance of developing appropriate differentiation protocols for
      tissue engineering therapies.

PMID- 18708176
TI  - Cortical and trabecular bone distribution in the femoral neck in osteoporosis and
      osteoarthritis.
AB  - The increased hip fragility in osteoporosis has been attributed mainly to a
      thinning of the cortex. In contrast, hip arthritis (OA) is not associated with
      increased risk of hip fracture. The purpose of this study was to assess cortical
      and trabecular bone structures and their possible regional variability in the
      femoral neck taken from patients who sustained an osteoporotic hip fracture (OP)
      compared with patients with OA. We compared the distribution of bone in the
      ultradistal femoral neck in 21 postmenopausal women with OA (mean age: 66+/-7.8
      years) and 20 postmenopausal women with an osteoporotic hip fracture (OP) (mean
      age: 79.5+/-1.9 years). Controlateral hip osteoporosis or osteopenia was
      confirmed in OP by DEXA (T-score: -2.5+/-0.8 in OP; -0.9+/-1.3 in OA).
      Histomorphometric parameters of bone structure, architecture and connectivity
      were measured on sections from the ultradistal part of the femoral neck, divided
      in 4 quadrants. When compared to OA, cortical thickness was significantly
      decreased in OP (p<0.0005) but was the highest in the inferior part in both
      groups. Cortical porosity was higher in OA (13.48+/-1.02 and 8.4+/-1.07% in OA
      and OP respectively). Compared to OA, the trabecular bone volume was decreased by
      50% in OP (p<0.0001) with a diminution of the trabecular number (p<0.01) and
      thickness (p<0.0001). In parallel, OP group was characterized by a poor
      connectivity evaluated by the decreased number of nodes (p<0.0001), higher
      trabecular bone pattern factor (p<0.0001) and greater marrow star volume
      (p<0.0001). The connectivity was the lowest in the inferior quadrant in OP but
      not in OA. Our data suggest that in addition to the cortical thinning, the loss
      of the trabecular bone mass and connectivity plays a role in the skeletal
      fragility associated with hip fracture. Furthermore, the spatial distribution of
      the trabeculae differs between OP and OA whereas cortical thinning is homogenous.

PMID- 18708175
TI  - Bax deficiency in mice increases cartilage production during fracture repair
      through a mechanism involving increased chondrocyte proliferation without changes
      in apoptosis.
AB  - This study sought to determine the role of the pro-apoptotic gene, Bax, in
      fracture healing by comparing femoral fracture healing in Bax knockout (KO) and
      wild-type C57BL/6J (background strain) mice. Bax KO fractures were larger, had
      more bone mineral content, had approximately 2-fold larger cartilage area per
      callus area in the first and second weeks of fracture healing, and showed an
      increased osteoclast surface area in the third and fourth weeks of fracture
      healing compared to C57BL/6J fractures. The increased cartilage area in the Bax
      KO fracture callus was due to increases in number of both pre-hypertropic and
      hypertropic chondrocytes. TUNEL analysis showed no significant differences in the
      number of either chondrocyte or non-chondrocyte apoptotic cells between Bax KO
      and C57BL/6J fractures at 7 or 14 days post-fracture, indicating that the
      increased number of chondrocytes in Bax KO fractures was not due to reduced
      apoptosis. Analysis of expression of apoptotic genes revealed that although the
      expression levels of Bcl-2 and Bcl-xL were not different between the Bax KO and
      C57BL/6J mice at 7 or 14 days post-fracture, the expression of BH3-domain only
      Bak and "Bik-like" pro-apoptotic gene increased approximately 1.5-fold and
      approximately 2-fold, respectively, in Bax KO fractures at 7 and 14 days post
      fracture, compared to C57BL/6J fractures, suggesting that up-regulation of the
      Bak and Bik-like pro-apoptotic genes in Bax KO mice might compensate for the lack
      of Bax functions in the context of apoptosis. Analysis by in vivo incorporation
      of bromodeoxyuridine into chondrocytes within the fracture tissues indicated a
      highly significant increase in chondrocyte proliferation in Bax KO fractures
      compared to C57BL/6J fractures at day 7. The increased expression of collagen
      2alpha1 and 9alpha1 gene in Bax KO fractures during early healing was consistent
      with an increased chondrocyte proliferation. In conclusion, this study
      demonstrates for the first time that Bax has an important role in the early stage
      of fracture healing, and that the increased callus size and cartilage area in Bax
      KO fractures was due to increased chondrocyte proliferation and not to reduced
      apoptosis or increased chondrocyte hypertrophy. The unexpected effect of Bax
      deficiency on chondrocyte proliferation implicates a novel regulatory function
      for Bax on chondrocyte proliferation during fracture repair.

PMID- 18708177
TI  - In vivo linear microcracks of human femoral cortical bone remain parallel to
      osteons during aging.
AB  - Previous studies have examined the density of microdamage within the cortex of
      long bones mostly from the viewpoint that is perpendicular to the long axis of
      the bone. The goal of the present work is to conduct a systematic
      characterization of the microcracks from a viewpoint that is parallel to the long
      axis of a load-bearing bone, the femur, so as to gain a better understanding of
      the size, shape and orientation of the microdamage. Longitudinal cross sections
      were taken at the mid-diaphysis of femurs from 13 male donors (23-85 years old)
      after being stained with basic fuchsin. The number of cracks, their lengths and
      orientation with respect to osteons were characterized using brightfield and UV
      epifluorescent imaging. The mean crack density was 0.1118+/-0.0417 mm(-2) in the
      longitudinal plane and it significantly increased with age. The median crack
      length along the longitudinal plane did not change with age. The crack length in
      the posterior quadrant was significantly lower than anterior, medial and lateral
      quadrants. Less than 3% of the cracks were longer than 1 mm, indicating the
      presence of 'in vivo macroscopic' cracks in bone tissue. It was observed that the
      99% of the cracks had angles that were less than 25 degrees with the osteons
      (median angle of 4.2 degrees with an interquartile range of 5.8 degrees ),
      indicating that the majority in vivo linear microcracks are parallel to osteons.
      This parallelism did not differ between quadrants nor changed with age. The
      remarkably stagnant crack length and crack orientation across decades of aging
      suggest that either physiological loading profile leading to these in vivo
      microcracks are not changing notably with age, or, microcrack and osteonal
      orientations may be relatively insensitive to age-related changes in locomotion.
      In conclusion, in vivo linear microcracks of the femoral mid-shaft grow in planes
      parallel to osteons and their lengths do not increase with age.

PMID- 18708178
TI  - Effects of estrogen receptor alpha- and beta-selective substances in the
      metaphysis of the tibia and on serum parameters of bone and fat tissue metabolism
      of ovariectomized rats.
AB  - The functions of estrogen receptors (ER) alpha and beta (ER-alpha and beta) in
      bone and fat tissue are not precisely described. Therefore we studied the effects
      of a specific ERalpha and ERbeta agonist in bone and fat of ovariectomized (ovx)
      rats and compared them with the effects of estradiol (E2). Animals were s.c.
      injected for 4-weeks with 3 doses of the ERalpha agonist 16alpha-LE2 or the
      ERbeta agonist 8beta-VE2 or with E2. The intermediate doses were antagonized by
      an additional daily treatment with ICI (1.53mg). Bone and fat parameters were
      evaluated by quantitative computer tomography (qCT). Estrogen regulated hormones
      were also measured. Uterine weights were stimulated; serum LH and leptin levels
      suppressed E2 and the ERalpha agonist. Density of the cancellous metaphyseal
      structures of the tibia was reduced in the controls which was prevented by E2 and
      the ERalpha agonist. Endosteal surface, endosteal, periosteal circumferences and
      fat depots were largest in the controls and the ERbeta treated animals and lowest
      in the E2 and the 16alpha-LE2 injected ovx rats. Osteocalcin and the CrossLaps
      were highest in the ovx controls and reduced by E2 and the ERalpha agonist. Serum
      osteocalcin was stimulated by the ERbeta agonist. The strain strength index (SSI)
      in relation to the bodyweight - an indicator of bone elasticity - was lowest in
      controls and increased dose dependently in the E2 and in the ERalpha treated
      animals. Most effects in the uterus, serum and bone were antagonized by ICI. Most
      effects in the bone and fat were exerted by mechanisms involving the ERalpha but
      the ERbeta agonist appears to stimulate osteoblasts.

PMID- 18708179
TI  - Monocular oral reading performance after amblyopia treatment in children.
AB  - PURPOSE: To evaluate the monocular oral reading rate, accuracy, fluency, and
      comprehension in 10-year-old children previously treated for amblyopia. DESIGN:
      Prospective, observational case series. METHODS: Seventy-nine children (mean age,
      10.3 years) previously treated in a multicenter randomized trial comparing
      patching and atropine were tested at seven sites using a modification of the Gray
      Oral Reading Test, Fourth Edition (GORT-4). RESULTS: The mean visual acuities
      (VA) in the amblyopic and fellow eyes at the time of the reading assessment were
      0.17 logarithm of the minimum angle of resolution (logMAR) units (approximately
      20/32) and -0.03 logMAR units (approximately 20/20), respectively. Compared with
      the sound eye, amblyopic eye performance was worse when reading orally with
      respect to rate (P < .001), accuracy (P = .03), and fluency (P < .001). Reading
      comprehension scores were similar with the amblyopic and fellow eyes (P = .45).
      Similar results were found with respect to original treatment group assignment
      (atropine or patching). There was a modest correlation between interocular
      difference (IOD) of VA at age 10 years and IOD in reading rate (r = 0.37; 95%
      confidence interval [CI], 0.18 to 0.56) and fluency (r = 0.28; 95% CI, 0.08 to
      0.49). There was no correlation between the IOD in VA and IOD in accuracy (r =
      0.08; 95% CI, -0.14 to 0.30) or comprehension (r = 0.16; 95% CI, -0.05 to 0.37).
      CONCLUSIONS: The monocular oral reading ability when measured with the GORT-4 was
      slightly worse when reading with previously treated amblyopic eyes compared with
      fellow eyes in terms of rate, accuracy, and fluency, but reading comprehension
      testing was similar.

PMID- 18708180
TI  - Role of anti-tubercular therapy in uveitis with latent/manifest tuberculosis.
AB  - PURPOSE: To assess the role of anti-tubercular therapy in uveitis with
      latent/manifest tuberculosis (TB). DESIGN: Retrospective, interventional case
      series. METHODS: A total of 360 patients from uveitis clinic with following
      inclusion criteria were studied: 1) complete clinical records of visual acuity,
      slit-lamp biomicroscopic examination, intraocular pressure, complications if any,
      and treatment records at the baseline and at all follow-up visits; 2) a
      documented positive tuberculin skin test (10 mm of induration or more) at 48 to
      72 hours; 3) evidence of active uveitis, i.e., cellular reaction in the anterior
      chamber with or without keratic precipitates, and/or active vitreous
      inflammation, retinal vasculitis, choroiditis, or neuroretinitis; 4) all known
      causes of infectious uveitis except TB and known noninfectious uveitic syndromes
      ruled out; and 5) a minimum one year of follow-up from the initiation of
      treatment. Of these, 216 patients (Group A) received four-drug anti-tubercular
      therapy and corticosteroids, and 144 patients (Group B) received corticosteroids
      alone. The main outcome measure was recurrence of inflammation after minimum six
      months of initiating treatment in each group. RESULTS: Recurrences reduced
      significantly (P < .001) in Group A (15.74%) as compared to Group B (46.53%) over
      a median follow-up of 24 and 31 months, respectively. The patients treated with
      anti-tubercular therapy with corticosteroids had decreased risk of developing
      recurrence of uveitis by approximately two-thirds as compared to those treated
      with corticosteroids alone. CONCLUSION: Addition of anti-tubercular therapy to
      corticosteroids in uveitis patients with latent/manifest TB led to significant
      reduction in recurrences of uveitis.

PMID- 18708181
TI  - Ocular inflammation in Behcet disease: incidence of ocular complications and of
      loss of visual acuity.
AB  - PURPOSE: To estimate the risk of structural ocular complications and loss of
      visual acuity (VA) in cases of Behcet disease (BD) and to evaluate potential risk
      and protective factors for these events. DESIGN: Retrospective cohort study.
      METHODS: A total of 168 consecutive patients with BD-associated ocular
      inflammation treated at five academic center ocular inflammation subspecialty
      practices were included. Clinical data for these patients were ascertained by
      standardized chart review. Main outcome measures included VA, structural ocular
      complications of inflammation, and intraocular pressure (IOP). RESULTS: Over a
      median follow-up of 1.05 years, the incidence of specific structural
      complications and IOP disturbances were common: the incidence rate of any ocular
      complication was 0.45 per eye-year (EY). Rates of loss of VA to 20/50 or worse
      and to 20/200 or worse were 0.12 per EY and 0.09 per EY, respectively. Risk
      factors for loss of VA during follow-up were persistent inflammatory activity,
      presence of posterior synechiae, presence of hypotony, and presence of elevated
      IOP. In a time-dependent analysis, current activity of ocular inflammation was
      associated with an increased risk of loss of VA to 20/50 or worse (relative risk
      [RR], 2.45; 95% confidence interval [CI], 1.1 to 5.5; P = .03) and to 20/200 or
      worse (RR, 2.67; 95% CI, 1.2 to 5.8; P = .01). CONCLUSIONS: Loss of VA and
      occurrence of ocular complications were common in patients with ocular
      inflammation associated with BD, even with aggressive therapy. Ongoing
      inflammation during follow-up, presence or occurrence of posterior synechiae,
      hypotony, and elevated IOP were associated with an increased risk of loss of VA.

PMID- 18708182
TI  - Using virtual reality to determine how emergency signs facilitate way-finding.
AB  - In this study, virtual reality was the tool used to construct an experimental
      space. Three scenarios - one without emergency signs, another with an old-version
      emergency sign, and the third with a new-version emergency sign - were created,
      after which 107 subjects, divided into three groups, engaged in an emergency
      escape game to determine if and how various emergency signs aid in way-finding in
      the event of an emergency. Under the presupposition that the minimum time needed
      for an emergency escape without any mistake occurring was 40s, we found that the
      average way-finding time in the scenario without any emergency signs was 123.8s,
      for the scenario with the new-version signs 84.8s, and for the scenario with the
      old-version signs 75.6s; statistically, this demonstrated that the absence of
      signs results in slower escape than either old signs (p=0.001) or new signs
      (p=0.005). These findings indicate that signs do help way-finding greatly. Males
      were found to exhibit better way-finding skills than females (p<0.001).
      Construction workers and fire safety personnel, as a combined group, did not fare
      better than others with less presumed prior experience with building plans or
      emergency exit procedures. In addition, when faced with both an emergency
      direction sign and an exit door, almost half of the subjects (42% of the
      participants) were chosen to take the door instead of following the direction
      posted on the sign. Finally, we found that, at T-intersections, the majority of
      participants (60%) chose to turn left versus right.

PMID- 18708184
TI  - Neuregulin 3 genetic variations and susceptibility to schizophrenia in a Chinese
      population.
AB  - BACKGROUND: The study investigated the possible association of NRG3 gene and
      schizophrenia in a Han Chinese population. METHODS: Of a total of 1345, 270
      unrelated schizophrenia inpatients, 235 normal control subjects, and 280 nuclear
      families (trios) with schizophrenia probands were studied. Nine single nucleotide
      polymorphisms (SNPs) spanning intron 1 to exon 9 of the NRG3 gene were analyzed,
      starting with the case-control samples. The SNPs showing significant association
      with schizophrenia in the case-control samples were subsequently studied in the
      independent trio samples with family-based association analysis. RESULTS: In case
      control samples, two SNPs (rs1937970 and rs677221) showed significant genotypic
      and allelic association with schizophrenia (all p < .05) with rs677221-C being
      the risk allele for schizophrenia (uncorrected p = .001, odds ratio = 1.439, 95%
      confidence interval = 1.115-1.858). Haplotypes GC constructed by the two SNPs was
      also significantly associated with schizophrenia (permutation p value = .0047).
      In the independent trio samples, rs1937970-A and rs677221-G consistently showed
      significant under-transmission to schizophrenic offspring (unadjusted p = .003
      and p = .004, respectively). In the haplotype-transmission disequilibrium test
      (TDT) for allelic combination of rs1937970-rs677221, significant under
      transmission for haplotype AG (uncorrected p = .006) and over-transmission for
      haplotype GC (uncorrected p = .004) to the affected schizophrenia offspring were
      observed. CONCLUSIONS: The result supports that the NRG3 gene is a susceptibility
      gene for schizophrenia.

PMID- 18708185
TI  - Multi-authors' self-citation: a further impact factor bias?

PMID- 18708183
TI  - Preclinical assessment for selectively disrupting a traumatic memory via
      postretrieval inhibition of glucocorticoid receptors.
AB  - BACKGROUND: Traumatic experiences may lead to debilitating psychiatric disorders
      including acute stress disorder and posttraumatic stress disorder. Current
      treatments for these conditions are largely ineffective, and novel therapies are
      needed. A cardinal symptom of these pathologies is the reexperiencing of the
      trauma through intrusive memories and nightmares. Studies in animal models
      indicate that memories can be weakened by interfering with the postretrieval
      restabilization process known as memory reconsolidation. We previously reported
      that, in rats, intraamygdala injection of the glucocorticoid receptor antagonist
      RU38486 disrupts the reconsolidation of a traumatic memory. Here we tested
      parameters important for designing novel clinical protocols targeting the
      reconsolidation of a traumatic memory with RU38486. METHODS: Using rat inhibitory
      avoidance, we tested the efficacy of postretrieval systemic administration of
      RU38486 on subsequent memory retention and evaluated several key preclinical
      parameters. RESULTS: Systemic administration of RU38486 before or after retrieval
      persistently weakens inhibitory avoidance memory retention in a dose-dependent
      manner, and memory does not reemerge following a footshock reminder. The efficacy
      of treatment is a function of the intensity of the initial trauma, and intense
      traumatic memories can be disrupted by changing the time and number of
      interventions. Furthermore, one or two treatments are sufficient to disrupt the
      memory maximally. The treatment selectively targets the reactivated memory
      without interfering with the retention of another nonreactivated memory.
      CONCLUSIONS: RU38486 is a potential novel treatment for psychiatric disorders
      linked to traumatic memories. Our data provide the parameters for designing
      promising clinical trials for the treatment of flashback-type symptoms of PTSD.

PMID- 18708186
TI  - Are drawing perseverations part of the neglect syndrome?
AB  - Unilateral neglect patients typically omit to cancel contralesional targets.
      Moreover, they can repeatedly cancel ipsilesional stimuli exhibiting what is
      termed 'perseverative behavior'. Two alternative accounts of this behavior have
      been proposed. According to one of them, it is considered as integral to neglect
      and due either to a perceptual (allochiria), or a premotor (directional
      hypokinesia) pathological mechanism leading to the ipsilesional displacement of
      contralesional responses. According to the other one, perseverations are
      interpreted as the consequence of motor-control-disinhibition co-occurring with,
      although independent of, spatial neglect. We compared some crucial predictions of
      these two hypotheses on a group of 10 right-brain-damaged patients, eight with
      neglect and two without neglect, showing a perseverative behavior in both
      conventional and experimental cancellation tasks. In our experiment, the spatial
      location and the numerosity of targets were manipulated to obtain different
      degrees of horizontal alignment between targets on the left and on the right of
      the central vertical axis of the sheet. We found that ipsilesional perseverations
      were not influenced by left neglected targets and were not correlated to neglect
      severity. Additionally, perseverative errors were associated with right basal
      ganglia lesions rather than with presence of neglect. These findings support the
      view that two different pathological mechanisms might be involved in left spatial
      neglect and ipsilesional perseverative behavior.

PMID- 18708187
TI  - Perseveration in left spatial neglect: drawing and cancellation tasks.
AB  - Perseveration in target cancellation tasks and in drawing by copy and from memory
      was investigated in 21 right-brain-damaged patients, seven with no evidence of
      left visuo-spatial neglect, and 14 with neglect. Eight such neglect patients
      showed perseveration in both cancellation and drawing tasks, although no
      correlation was found with the severity of neglect. Patients with perseveration
      were not disproportionately impaired in tasks assessing executive (fluency,
      Stroop colour-word interference, and Weigl's sorting test), and visuo-spatial
      short-term memory function. In the context of a two-component hypothesis, graphic
      perseveration (the first component) is a specific disorder that manifests in a
      variety of tasks, particularly those requiring serial graphic production.
      Unilateral spatial neglect (the second component) may trigger and facilitate the
      production of perseveration errors, with a contra-ipsilateral gradient of
      increasing severity.

PMID- 18708188
TI  - Closing-in without severe drawing disorders: the "fatal" consequences of
      pathological attraction.
AB  - The closing-in phenomenon (CIP) is often observed in patients with severe drawing
      disorders, but its cognitive bases are not well understood. We describe an
      experimental investigation aimed to clarify the nature of closing-in and its
      relationships with drawing disorders in a patient with corticobasal degeneration.
      In copying simple or complex stimuli (Experiment 1), the patient showed adherent
      and near types of closing-in, not affected by stimulus complexity, and produced
      distorted and often unrecognisable drawings. On the contrary, in drawing to
      dictation (without any available model), patients' performances significantly
      improved with respect to copying (Experiment 2). These data were consistent with
      the hypothesis that in some patients closing-in may develop from frontal-related
      release of approach behaviour even in the absence of relevant visuoperceptual
      impairments. By asking the patient to reproduce given spatial locations within
      circular frames (Experiment 3), we could further demonstrate the sparing of
      visuospatial processing and the frontal genesis of closing-in. These findings
      allowed us to speculate on the heterogeneous nature of closing-in.

PMID- 18708189
TI  - Prenatal diagnosis of chromosomal abnormalities in a resource-poor setting.
AB  - OBJECTIVE: To compare the efficacy and efficiency of systematic, ultrasound-based
      risk adjustment using a published algorithm with that of a maternal age cutoff of
      37 years for the prenatal detection of chromosomal abnormalities (especially
      autosomal trisomies). METHODS: These approaches were compared in a retrospective
      study of 136 chromosomal abnormalities confirmed by karyotyping prenatally (n=46)
      or postnatally (n=90). There were 114 autosomal trisomies. RESULTS: Maternal age
      was known for 103 fetuses with confirmed abnormalities. The ultrasound-based risk
      adjustment approach was more sensitive for autosomal trisomy (93.9% vs 44.1%),
      and karyotyping for younger women with abnormalities on ultrasound was more
      effective than routine karyotyping in older women (1 trisomy detected in 13.5 vs
      42.8 samples, P<0.001). A lack of screening was the main reason for the postnatal
      diagnosis. CONCLUSION: Ultrasound-based risk adjustment was the more effective
      approach.

PMID- 18708190
TI  - Swine hemi-facial composite tissue allotransplantation: a model to study immune
      rejection.
AB  - OBJECTIVE: Partial face composite tissue allotransplantation was recently
      achieved in a human subject. However, the side effects of long-term
      immunosuppression and chronic rejection area still need concerning. This
      preliminary study investigated the reproducibility of swine hemi-facial
      transplantation for preclinical studies. MATERIALS AND METHODS: Eleven out-bred
      miniature swine underwent hemi-facial transplant. The hemi-facial orthotopic
      transplant consisted of ear cartilage, auricular nerve, parotid gland and
      lymphoid tissue, muscle with surrounding hemi-facial skin paddle supplied by the
      carotid artery, and external jugular vein transplanted to recipient swine. Three
      different experimental designs were studied, as follows: group I (n = 4):
      autologous hemi-facial transplantation as a normal control; group II (n = 4):
      hemi-facial allotransplantation without treatment; group III (n = 3): hemi-facial
      allotransplantation with cyclosporine-A treatment for 4 wk. The transplanted face
      was observed daily for signs of rejection. Biopsy of donor skin, gland lymphoid
      tissue, and cartilage were obtained at specified predetermined time (d 7, 14,
      28), or at the time of clinically evident rejection. RESULTS: The results
      indicated the survival of group I following autologous hemi-facial transplant was
      100% and indefinite until sacrifice. Group II without treatment as the controls
      revealed allograft rejection by d 7 to 28. The allograft with short-term
      cyclosporine-A treatment revealed delayed rejection by d 38 to 49
      postoperatively. The histological examination in group I revealed abundant
      lymphocyte infiltration, especially in lymphoid gland and alloskin at 1 wk and
      sacrifice. In contrast, the cyclosporine treatment group showed no significant
      rejection signs in 4 wk posttransplants. These results demonstrated that lymphoid
      tissue and alloskin are both susceptible to early rejection. CONCLUSION: The
      experimental results revealed this model is suitable to investigate the new
      strategies for preclinical facial allotransplantation studies. Monitoring and
      modulation of early rejection in alloskin and gland lymphoid tissue is a useful
      strategy to evaluate composite tissue allotransplantation survival.

PMID- 18708191
TI  - Intravenous glutamine enhances COX-2 activity giving cardioprotection.
AB  - BACKGROUND: Preconditioning, a highly evolutionary conserved endogenous
      protective response, provides the most powerful form of anti-infarct protection
      known. We investigated whether acute intravenous glutamine, through an effect on
      cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce
      preconditioning. MATERIALS AND METHODS: Male New Zealand white rabbits (n = 28)
      received either 0.5 g/kg glutamine in 0.9% saline or saline only in divided doses
      for 3 d. The large marginal branch of the left coronary was occluded for 30 min;
      cardiac function was assessed during 3 h of reperfusion, and infarct size was
      measured. 6-Keto-PGF-1alpha, nitrate, and malonaldehyde serum levels were
      determined. Hearts were taken from a further group of pretreated rabbits (n = 10)
      to assess myocardial COX-2 and HSP72 levels. RESULTS: Glutamine pretreatment
      resulted in a 39% reduction in infarct size (30.7 +/- 2.0% versus 50.4 +/- 2.1%
      controls; P < 0.01). Myocardial COX-2 levels were significantly elevated with
      pretreatment (P < 0.05) and were mirrored by higher serum 6-keto-PGF-1alpha
      levels prior to ischemia (69 +/- 13 versus 18 +/- 21 pg/mL in controls, P =
      0.027). There was no significant difference in myocardial HSP72 or serum nitrate
      levels following pretreatment, or malonaldehyde levels during reperfusion.
      CONCLUSIONS: Glutamine pretreatment confers anti-infarct protection through up
      regulation of COX-2, a key mediator of delayed preconditioning protection.
      Previous confirmation of its clinical safety profile at these doses suggests an
      acceptable strategy for inducing preconditioning for perioperative protection.

PMID- 18708192
TI  - One-lung ventilation during thoracoabdominal esophagectomy elicits complement
      activation.
AB  - BACKGROUND: One-lung ventilation (OLV) during thoracoabdominal esophagectomy may
      induce an inflammatory response that can contribute to the induction and
      propagation of frequently occurring postoperative respiratory distress. Markers
      of such a response might be detected in the pulmonary as well as in the systemic
      circulation. Inflammation and tissue damage may be key pathogenetic pathways and
      we hypothesized that 1-lung ventilation may induce an inflammatory cascade
      reflected by markers for such a response. MATERIALS AND METHODS: Thirty patients
      with esophageal cancer were randomized to OLV (n = 16) or 2-lung ventilation
      (TLV; n = 14) during the thoracic part of the operation. Compounds involved in
      inflammation and coagulation were measured perioperatively and during the 1st,
      2nd, 3rd, and 10th postoperative d. RESULTS: During the perioperative phase, the
      proinflammatory cytokine interleukin-6 and thrombin, measured as thrombin
      antithrombin complexes, started to increase. Thrombin, which can induce
      complement activation, peaked at the end of surgery and interleukin-6 at the 1st
      to 2nd postoperative d, but there were no differences between the OLV and TLV
      groups. C3a and terminal complement complex (TCC) started to increase on the 2nd
      postoperative d and continued to do so for the rest of the study period. The
      increase of TCC was significantly higher in the OLV group compared to the TLV
      group, whereas C3a attained similar levels in the 2 groups. CONCLUSIONS: OLV is
      associated with an augmented inflammatory response as reflected by the activation
      of the TCC. This may induce pulmonary tissue damage and recruitment of
      inflammatory cells.

PMID- 18708193
TI  - The oxidative response in the chronic constriction injury model of neuropathic
      pain.
AB  - BACKGROUND: In the chronic constriction injury model of rat neuropathic pain,
      oxidative stress as well as antioxidants superoxide dismutase and reduced
      glutathione (GSH) are important determinants of neuropathological and behavioral
      consequences. Studies of the chronic constriction injury model observed
      (indirect) signs of inflammation. We, therefore, investigated the level of
      oxidative stress and antioxidant enzymes in skeletal muscle tissue of the rat
      hind paw and (jugular vein) plasma at d 7 after nerve injury. MATERIALS AND
      METHODS: The level of reactive oxygen and nitrogen species (RONS) was determined
      as a measure of oxidative stress. Reduced GSH levels and the
      ceruloplasmin/transferrin ratio were determined as measures of overall
      antioxidant activity. RONS and overall antioxidant activity were measured in
      skeletal muscle tissue of the hind paw and jugular vein plasma. The level of RONS
      in muscle was determined using spin trapping combined with electron paramagnetic
      resonance spectroscopy. Using electron paramagnetic resonance spectroscopy, we
      also determined plasma levels of transferrin and ceruloplasmin. GSH levels were
      determined using high-performance liquid chromatography. RESULTS: In skeletal
      muscle tissue, the level of RONS was lower in nerve-injured hind paws than in
      controls. The plasma level (jugular vein) of RONS did not differ between nerve
      injured and control rats. In skeletal muscle tissue, the level of GSH was higher
      in nerve-injured hind paws than in controls. The ceruloplasmin/transferrin ratio
      tended to be higher in (jugular vein) plasma of nerve-injured rats as compared to
      controls. CONCLUSIONS: This study shows that, at d 7 after nerve injury,
      oxidative stress-induced changes are present also in skeletal muscle tissue of
      the rat hind paw. Our findings of a decreased level of RONS in combination with
      an increased level of the antioxidant GSH suggest that an overshoot of
      antioxidant activity overrules initial oxidative stress.

PMID- 18708194
TI  - Assessment of colorectal cancer prognosis through nuclear morphometry.
AB  - BACKGROUND: Due to the fact that different biological parameters play a key role
      in colonic malignant behavior, with nuclear morphometry being a prognostic marker
      in many malignancies, then predictive approaches in colorectal cancer (CRC)
      carried out on histologically well-defined groups may prevent interpretative
      errors. Subsequently, in the present study, CRC patients were screened according
      to the morphometric features of tumor cell nuclei, using an accurate
      histotechnical approach, to analyze their clinical evolution according to Dukes'
      stratification. MATERIALS AND METHODS: A total of 66 cases were grouped according
      to Dukes' classification (5 y of follow-up). The perimeter, nuclear area, and
      shape factor of 50 interphase carcinoma nuclei were recorded through
      microphotographs obtained from each subject. Nuclei boundaries were drawn by an
      electronic pencil and examined by a computerized system. Data were submitted to a
      variance analysis, and a multi-regression model compared results. RESULTS: The
      sample was made up of 44 males (66.67%) and 22 females (33.33%) aged 59.7 +/- 6 y
      old. Forty-nine patients (74.24%) were classified as stage B, and 17 (25.76%) as
      stage C. Nuclear homogeneity was confirmed by analysis of variance. The nuclear
      parameters were (mean +/- SD): area (3.17 +/- 1.74), perimeter (6.72 +/- 1.83),
      and shape factor (0.82 +/- 0.03). A multiple logistic regression model showed
      that stage C subjects had a higher risk of developing a worse clinical evolution
      than those at stage B (P < 0.02), independent of sex and age. CONCLUSIONS: Dukes'
      classification remains the best predictor of evolution. Although
      nucleomorphometric suitability is still controversial, this technique has become
      an additional tool to establish CRC prognosis.

PMID- 18708195
TI  - Wound healing on athymic mice with engineered skin substitutes fabricated with
      keratinocytes harvested from an automated bioreactor.
AB  - The Kerator is a computer controlled bioreactor for the automated culture and
      harvest of keratinocytes that can reduce labor and materials involved in the
      fabrication of engineered skin substitutes (ESS). Previous studies have shown
      that the Kerator is comparable to tissue culture flasks by keratinocyte
      confluence during culture, clonogenic potential of harvested keratinocytes and
      microanatomy, cell viability, and surface hydration of ESS fabricated with the
      harvested keratinocytes. In this study, the Kerator and tissue culture flasks
      were further compared by keratinocyte proliferation in vitro and wound healing
      after transplantation of ESS to athymic mice. The number of bromodeoxyuridine
      positive keratinocytes in ESS fabricated with keratinocytes harvested from
      Kerator after 2 wk of in vitro maturation was 34 +/- 3 per high power field (hpf)
      (mean +/- SEM), which was not significantly different from that fabricated with
      keratinocytes harvested from flasks (34 +/- 1.5 per hpf). Percentage original
      wound area 6 wk after surgery of ESS fabricated with keratinocytes from the
      Kerator was 36% +/- 3.3%, which was not significantly different from that of ESS
      fabricated with keratinocytes from flasks (30% +/- 4.3%). In both cases, 78% (7
      of 9) mice transplanted were positive for engraftment of human keratinocytes by
      direct immunofluorescence for HLA-ABC antigens. These results further confirm
      that the ESS fabricated with keratinocytes harvested from Kerator and flasks are
      equivalent in vitro and in vivo. Therefore, use of Kerator for large scale
      production of ESS can lead to increased availability at reduced cost while
      maintaining ESS quality for grafting.

PMID- 18708196
TI  - Angiogenesis and tumor progression in neuroendocrine digestive tumors.
AB  - BACKGROUND: Clinical observations suggest that in neuroendocrine digestive tumors
      a high intratumoral microvascular density is associated with good prognosis. We
      used an experimental orthotopic xenograft model to analyze the relations between
      angiogenic activity and tumor progression in this tumor subset. MATERIAL AND
      METHODS: We compared 2 endocrine cell lines: STC-1, a low vascular endothelial
      growth factor (VEGF)-producing cell line, and INS-r3, a high VEGF-producing cell
      line. Tumor cells were grafted in the adventitial layer of the caecal wall of
      nude mice, sacrificed after 8 wk. RESULTS: At 8 wk, "primary" tumors were present
      in all animals. STC-1 derived tumors were morphologically moderately
      differentiated, with high proliferative and apoptotic activities; in contrast,
      INS-r3 derived tumors were well differentiated, with low proliferative and
      apoptotic activities. VEGF was expressed in <50% grafted STC-1 cells but in >90%
      of grafted INS-r3 cells. Microvascular density was significantly higher in INS-r3
      derived tumors than in STC-1 derived tumors. All STC-1 derived tumors (n = 8)
      have invaded the mucosa, in contrast to none of the INS-r3 derived tumors (n =
      8); liver metastases were detected in 7/8 animals bearing STC-1 derived tumors
      and in 0/8 animals with INS-r3 derived tumors, despite the presence of lymph node
      metastases. CONCLUSIONS: Our experimental data concur with clinical findings to
      suggest that in well differentiated digestive neuroendocrine tumors angiogenesis
      is disconnected from tumor progression: the development of a highly vascular
      tumor microenvironment is correlated with VEGF secretion but is not associated
      with invasive and metastatic properties; it must therefore be regarded as an
      indirect marker of differentiation.

PMID- 18708197
TI  - Generation and modulation of hepatocellular carcinoma circulating cells: a new
      experimental model.
AB  - BACKGROUND: To establish a new experimental model of human hepatocellular
      carcinoma by orthotopic implantation of tumoral cells with its subsequent
      removal, to generate and modulate circulating tumoral cells. MATERIALS AND
      METHODS: Three human hepatoma cell lines (HepG2, PLC/PRF, and Mahlavu) were
      orthotopically implanted under the Glisson's capsule of the left lateral lobe of
      the liver in a total of 56 non-obese diabetic/severe combined immunodeficiency
      mice. Tumor removal was performed 30 d after injection, and a laparotomy without
      tumor removal was done in control mice. Generation of circulating cells was
      monitored by flow cytometry using fluorescein isothiocyanate-conjugated anti-HLA
      antibody. RESULTS: In 26 mice implanted with Mahlavu cells, 20 developed a unique
      tumor allowing a resection (77%), which was technically feasible in 80% of cases.
      The overall perioperative mortality was 30% (3/10) after resection; no mortality
      was observed in the control group. The circulating tumoral cells decreased
      dramatically after resection of the tumor as compared with control mice.
      CONCLUSION: This new model is feasible and may be an interesting useful tool to
      study the hepatocellular carcinoma metastatic process and is consistent with the
      human clinical practice.

PMID- 18708198
TI  - Management of neural tube defects in a Sub-Saharan African country: the situation
      in Yaounde, Cameroon.
AB  - BACKGROUND: Neural tube defect is a serious disabling but preventable congenital
      malformation with an incidence of 1.99 per 1000 births in Yaounde [A.K. Njamnshi,
      V. d e P. Djientcheu, A. Lekoubou, M. Guemse, M.T. Obama, R. Mbu, S. Takongmo, I.
      Kago. Neural tube defects are rare among black Americans but not in Sub-Saharan
      black Africans: The case of Yaounde-Cameroon. Journal of the Neurological
      Sciences 2008; 270: 13-17]. The management requires highly qualified personnel
      and a significant social cost. The aim of this study was to evaluate the
      management of neural tube defect in a resource-limited developing Sub-Saharan
      nation like Cameroon. METHODS: We reviewed all patients with neural tube defects
      admitted in the neonatology unit of the Mother and Child Center (Chantal Biya
      Foundation Yaounde) between January 1st 2000 and December 31st 2006. RESULTS:
      Sixty-nine (69) patients were enrolled. There was a male predominance (69.57%) in
      the sample. Myelomeningomecele represented 68.11% of cases, followed by
      encephalocele (27.54%) and meningocele (4.35%). Antenatal ultrasound examinations
      were done in 27 cases (32.8%). The prenatal diagnosis was made only in 8 cases.
      No medical abortion was performed in any of these cases. Medical abortion is
      illegal in Cameroon (except in certain specific situations) as well as other Sub
      Saharan African countries. Hydrocephalus was diagnosed in 40.02% of cases. As
      most of the patients (62.32%) could not afford modern treatment, only 26.09% of
      them were operated at birth. The rest sought traditional and other forms of
      treatment, due to poverty or cultural beliefs. Eight patients (11.59%) died
      before surgery. Surgery consisted of local closure alone (40%) or local closure
      associated to CSF shunting (60%). The complications were wound dehiscence
      (13.69%), shunt infection (1.37%), meningitis (1.37%) and iatrogenic pulmonary
      oedema (1.37%). CONCLUSION: Neural tube defects are the most frequent and
      disabling malformations in neonates in the Sub-Saharan African paediatric
      environment. Prenatal management and outcome at birth are limited by poverty and
      cultural beliefs. Prevention is possible and may be better than palliative care
      in developing countries.

PMID- 18708207
TI  - Reliability assessment of Society for Fetal Urology ultrasound grading system for
      hydronephrosis.
AB  - PURPOSE: The Society for Fetal Urology introduced a subjective grading system for
      classifying hydronephrosis that has important implications in patient diagnosis,
      treatment and outcome. The grading system is frequently used to standardize the
      severity of hydronephrosis, and compare results among patients and centers.
      Despite widespread use to our knowledge no groups have investigated the
      reliability of the grading system since its introduction. We assessed the
      intrarater and interrater reliability of the Society for Fetal Urology grading
      system for hydronephrosis and examined levels of agreement by the degree of
      hydronephrosis (grades 0 to 4) and level of experience (staff vs trainee).
      MATERIALS AND METHODS: A series of 50 pediatric renal ultrasound images from
      patients with a diagnosis of hydronephrosis were assessed by 4 staff individuals
      and 4 trainees using the Society for Fetal Urology grading system. Ultrasound
      images included the kidneys, ureters and bladder to be consistent with practice.
      After 7 to 14 days each rater repeated the assessment. The nonweighted Cohen
      kappa statistic was used to estimate intrarater and interrater reliability by
      Society for Fetal Urology grade and training level. RESULTS: Staff and trainee
      raters independently assigned Society for Fetal Urology grades to 50 patients (99
      renal units). The average number of images per ultrasound was 41, including the
      right and left kidneys. Overall interrater agreement for staff individuals was
      substantial for grade 0, moderate for grades 1, 2 and 4, and only slight to fair
      for grade 3. Intrarater agreement was substantial to almost perfect for staff
      agreement (range 69% to 94%, kappa 0.56 to 0.89) and trainees (range 63% to 90%,
      kappa 0.48 to 0.85). CONCLUSIONS: Our study suggests that the Society for Fetal
      Urology grading system has good intrarater but modest interrater reliability.
      Individual rater interpretations of the grading system may explain the modest
      interrater agreement. Proposed modifications to the Society for Fetal Urology
      classification system, such as distinguishing between diffuse and segmental
      cortical thinning, may improve reliability.

PMID- 18708209
TI  - Surgical management of congenital ureteropelvic junction obstruction: a Pediatric
      Health Information System database study.
AB  - PURPOSE: Although laparoscopic pyeloplasty has gained popularity, to our
      knowledge no multi-institutional study has evaluated the prevalence of this
      approach in children. We used a multicenter database to determine trends in the
      treatment of congenital ureteropelvic junction obstruction. MATERIALS AND
      METHODS: The Pediatric Health Information System database contains data on 37
      freestanding hospitals for children across the United States. We extracted data
      on 0 to 19-year-old patients from 2001 to 2006 with the ICD-9 diagnosis code for
      congenital ureteropelvic junction obstruction and the procedure code for the
      correction of ureteropelvic junction obstruction. We identified laparoscopic
      cases based on hospital charges for 1) laparoscope, 2) trocar, 3) insufflating
      needle or 4) insufflator and tubing. Data were then analyzed using the chi-square
      and Student t tests to determine management trends. RESULTS: We identified 2,353
      patients, of whom 2,177 (92.5%) underwent open pyeloplasty and 176 (7.5%)
      underwent laparoscopic pyeloplasty. The percent of pediatric pyeloplasties
      performed laparoscopically increased from 2001 to 2003 (2.53% to 9.73%) and has
      since remained stable. Patients undergoing laparoscopic pyeloplasty were
      significantly older than those in the open group (age 8.2 vs 3.3 years, p
      <0.0001). Average hospital charges were significantly higher in the laparoscopic
      group than in the open group ($23,295.71 vs $16,467.49, p <0.05). There was no
      significant difference in terms of race, gender or length of stay. CONCLUSIONS:
      The percent of pediatric pyeloplasties performed laparoscopically has increased
      with time. However, laparoscopic pyeloplasty is associated with higher hospital
      charges than open surgery without a significant decrease in length of stay.

PMID- 18708210
TI  - Mini-ureteroneocystostomy: a safe and effective outpatient treatment for
      unilateral vesicoureteral reflux.
AB  - PURPOSE: Medically refractory vesicoureteral reflux is a common condition that
      can be cured by open surgery. Extravesical ureteroneocystostomy is a safe and
      effective surgical procedure. We determined whether this could be accomplished
      with limited dissection via an approximately 2 cm inguinal incision (mini
      ureteroneocystostomy). MATERIALS AND METHODS: All patients with unilateral
      vesicoureteral reflux who underwent mini-ureteroneocystostomy from 2003 to 2007
      were evaluated. We present preoperative characteristics, surgical technique and
      outcomes in this analysis. RESULTS: From 2003 to 2007, 57 children underwent mini
      ureteroneocystostomy for unilateral vesicoureteral reflux. The group was
      predominantly female (48 of 57 patients or 84%) with median age of 4.8 years.
      Median vesicoureteral reflux grade was 3 (range 2 to 5). Duplication anomalies
      were present in 8 patients, while 5 had a Hutch diverticulum and 5 had a solitary
      kidney. A total of 47 patients (82%) underwent postoperative voiding
      cystourethrogram and surgical cure was achieved in all. De novo vesicoureteral
      reflux was identified in the contralateral ureter in 3 of 47 patients (6%). The
      procedure was performed on an outpatient basis in 47 of 57 patients (82%).
      Postoperative complications requiring surgical intervention developed in 2
      children. CONCLUSIONS: Mini-ureteroneocystostomy is an effective modified
      extravesical technique for vesicoureteral reflux. This procedure is safe and it
      can be performed on an outpatient basis with excellent results. It has become our
      standard of care in patients with unilateral vesicoureteral reflux.

PMID- 18708213
TI  - Pressure, fluid and anatomical characteristics of abdominoscrotal hydroceles in
      infants.
AB  - PURPOSE: Abdominoscrotal hydrocele is a poorly understood entity and multiple
      theories attempt to explain its occurrence. To our knowledge the factors
      contributing to the formation of abdominoscrotal hydrocele are unknown, as are
      its cellular, biochemical and hydrostatic properties. We prospectively evaluated
      abdominoscrotal hydrocele at surgery to define its cause and its effects on the
      testicle. MATERIALS AND METHODS: Six patients (9 abdominoscrotal hydroceles) were
      prospectively evaluated at surgery. Hydrocele volume was recorded as well as
      simultaneous hydrocele and bladder pressure. Fluid at surgery was sent for
      biochemical and cellular analysis. Testicular and epididymal abnormalities were
      noted and testicular length was measured. All abdominoscrotal hydroceles were
      exteriorized and excised. Processus vaginalis patency was documented at repair.
      RESULTS: Mean patient age was 7.17 months (range 5 to 12). The mean volume
      recorded was 212.78 ml (range 80 to 320). Mean corrected hydrocele pressure was
      15.44 cm H(2)O (range 7 to 28). Mean testicular length was 3.6 cm (range 2.2 to
      5.5). All patients had epididymal anomalies and 2 of the 3 unilateral
      abdominoscrotal hydroceles had abnormal contralateral scrotal findings. In no
      case was a peritoneal communication identified. Fluid analysis revealed a high
      protein concentration (mean 4.94 gm/dl), low triglyceride concentration (mean
      20.29 mg/dl) and lactate dehydrogenase levels comparable to those in normal serum
      (mean 99.14 U/l). Cytological analysis revealed a sterile, low cellularity fluid
      with a macrophage predominance (mean 84.71%). CONCLUSIONS: Abdominoscrotal
      hydrocele occurs as a result of increased intraluminal pressure confined in a
      proximal closed processus vaginalis. Increased hydrocele pressure allows
      expansion into the retroperitoneal space through the internal inguinal ring. This
      increased pressure is associated with testicular elongation and epididymal
      abnormalities. The exudative fluid is of a noninfectious etiology and it suggests
      an altered filtration process. To our knowledge the effects on future fertility
      are unknown.

PMID- 18708214
TI  - Paraexstrophy skin flaps for the primary closure of exstrophy in boys: outmoded
      or updated?
AB  - PURPOSE: We evaluated the current application of Duckett paraexstrophy skin flaps
      for bladder exstrophy reconstruction. MATERIALS AND METHODS: We reviewed the
      records of cases of classic exstrophy treated at our institution between
      September 1993 and March 2007. A total of 21 patients were identified in whom
      modified Duckett paraexstrophy skin flaps were used in bladder closure at our
      institution. Another 12 patients were referred during the same time after closure
      with complications with flap use. RESULTS: Of the 21 patients who underwent
      closure at our institution with our modified version of the Duckett flaps 1 (4%)
      had a complication, that is urethral stricture. This responded to internal
      urethrotomy and daily intermittent catheterization for 4 months, and the
      stricture stabilized. Four of the 12 referred patients responded to multiple
      urethral dilations, 3 underwent open repair with a buccal graft, 2 received a
      full-thickness skin graft and 3 underwent internal urethrotomy with daily
      intermittent catheterization for 4 months. Of our 21 patients with internal
      treatment 14 underwent bladder neck repair, 5 underwent epispadias repair and 2
      were awaiting further reconstruction. Six of the 12 referred patients underwent
      bladder neck repair, 4 underwent epispadias repair and 2 were awaiting further
      reconstruction. CONCLUSIONS: By modifying our version of the Duckett
      paraexstrophy skin flaps we have lowered our complication rate significantly.
      While overall use of these flaps has continued to decrease, when they are
      required, these modifications help avoid complicating strictures and their
      sequelae in the bladder and upper urinary tract.

PMID- 18708215
TI  - Varicocelectomy in adolescent boys: long-term experience with the Palomo
      procedure.
AB  - PURPOSE: We report our long-term experience with the Palomo technique for
      varicocele ligation in the pediatric population. MATERIALS AND METHODS: Between
      August 1986 and December 2006, 312 patients 7 to 21 years old (median age 14.6)
      underwent varicocele ligation using the Palomo technique for complete
      retroperitoneal ligation of the internal spermatic veins and artery. In 234
      patients the varicocele was grade III, in 75 it was grade II and in 3 it was
      grade I. Indications for surgery were relative left testicular volume loss
      compared to the right testicle in 248 patients, bilateral palpable varicoceles in
      8 and pain or parental preference in the remainder. Postoperative followup was 2
      weeks to 10.6 years (mean 17.4 months). A total of 233 patients had at least a 6
      month followup. RESULTS: Persistent varicocele was noted in 9 of 233 patients
      (3.9%). Of the 233 patients 68 (29%) presented with a secondary hydrocele an
      average of 14 months (range 18 to 1,964 days) following surgery, of whom 12
      (17.6%) underwent hydrocele correction. The 12 patients who underwent
      hydrocelectomy represented 5% of the patients with varicocelectomy. Postoperative
      testicular atrophy was not documented in any patient and no other surgical
      complications were noted. CONCLUSIONS: The Palomo procedure for adolescent
      varicocele repair is safe and effective with a high success rate and low
      complication rate. Postoperative hydrocele formation developed in 29% of our
      patients. However, most secondary hydroceles were small, asymptomatic and did not
      require surgical correction.

PMID- 18708220
TI  - Outcome analysis and cost comparison between externalized pyeloureteral and
      standard stents in 470 consecutive open pyeloplasties.
AB  - PURPOSE: Despite the widespread use of ureteral stents for pyeloplasty by
      pediatric urologists there is ongoing controversy regarding the most advantageous
      type of transanastomotic drainage. We compared patients who underwent placement
      of an externalized pyeloureteral Salle intraoperative pyeloplasty stent (Cook
      Urological, Spencer, Indiana) to those who had a standard Double-J ureteral stent
      placed to assess the benefits, drawbacks and costs of each modality during open
      pyeloplasty. MATERIALS AND METHODS: Our study sample comprised 470 age matched
      children who underwent primary open pyeloplasty in an 11-year period. A total of
      242 patients (51.5%) underwent Double-J ureteral stent insertion and 228 (48.5%)
      underwent placement of a Salle intraoperative pyeloplasty stent at surgery.
      Operative time, hospital stay, overall complication and success rates, type of
      complications and hospital costs were compared between the 2 groups. RESULTS:
      Median age was 18 months and median followup was 39 months. Mean hospital stay
      was 3.0 and 3.1 days in children with a Double-J ureteral and a Salle
      intraoperative pyeloplasty stent, respectively (p = 0.7). The overall
      complication rate was 9.9% (24 of 242 patients) for the Double-J ureteral stent
      vs 8.3% (19 of 228) for the Salle intraoperative pyeloplasty stent (p = 0.6).
      Complications in patients with a Double-J ureteral stent consisted of urinoma in
      3, return visits due to bladder spasms in 7 or catheter obstruction in 6 and
      readmission due to pyelonephritis in 5. Complications in children with a Salle
      intraoperative pyeloplasty stent involved urinoma in 1, prolonged drainage
      through the Penrose drain in 5 and readmission due to pyelonephritis in 1.
      Recurrent ureteropelvic junction obstruction developed in 12 cases per group. The
      success rate was 95.0% (230 of 242 cases) and 94.7% (216 of 228) for the Double-J
      ureteral and the Salle intraoperative pyeloplasty stent, respectively (p = 0.2).
      Hospital charges, including the surgical procedure, postoperative hospitalization
      and cystoscopy or a clinical visit for catheter removal, in patients with a
      Double-J ureteral and a Salle intraoperative pyeloplasty stent were $9,825 and
      $9,260, respectively. CONCLUSIONS: The 2 ureteral stents are equivalent in regard
      to overall complication and success rates after pyeloplasty. However, Salle
      intraoperative pyeloplasty stent insertion was associated with a Canadian $565
      cost decrease per patient and most importantly the preclusion of a second general
      anesthesia for catheter removal.

PMID- 18708223
TI  - 3-dimensional neuroanatomy of the human fetal pelvis: anatomical support for
      partial urogenital mobilization in the treatment of urogenital sinus.
AB  - PURPOSE: Retrospective reviews suggest that the functional outcomes of surgery of
      the urogenital sinus have often been unsatisfactory and to our knowledge the long
      term results of newer surgical techniques have yet to be evaluated. A precise
      understanding of pelvic fetal neuroanatomy is germane for optimizing surgical
      correction of the urogenital sinus. MATERIALS AND METHODS: The pelves of 10 human
      female fetuses were serially sectioned. Masson's trichrome staining and
      immunochemistry for the neuronal marker S100 (Dako Corp., Carpinteria,
      California) along with anatomical computer reconstruction allowed 3-dimensional
      analysis of the nerves in relation to the pelvic structures as an animated motion
      picture. RESULTS: Two types of neuronal structures were identified. 1) A dense
      perivisceral foil of branching nerves closely surrounded the pelvic organs. The
      localization of most nerves was on the external faces of the viscera with a
      limited fraction in the rectovaginal and urethrovaginal septa. This innervation
      was from the anterior cephalad periurethral area to the posterior caudal
      perirectal area. 2) A significant amount of nerves surrounded the cephalad
      urethra on its anterior and posterior faces. CONCLUSIONS: Based on these
      anatomical data during surgical repair of a urogenital sinus we would advocate
      minimal mobilization of the lateral faces of the vagina, avoiding dissection of
      the proximal urethra above the pubic bone and electing a vaginal flap in severe
      cases.

PMID- 18708224
TI  - Risk factors for end stage renal disease in children with posterior urethral
      valves.
AB  - PURPOSE: Obstructive uropathy secondary to posterior urethral valves is an
      important cause of end stage renal disease in children. Early diagnosis and
      intervention to decrease bladder pressure and stabilize the upper urinary tract
      are important to delay or prevent the progression of renal insufficiency. We
      analyzed the records of patients with posterior urethral valves to determine risk
      factors that might be predictive of ultimate renal failure. MATERIALS AND
      METHODS: A retrospective cohort study was performed of children presenting to our
      institution with a diagnosis of posterior urethral valves from 1975 to 2005.
      Patient demographics, clinical background, laboratory and radiographic data, and
      renal outcomes were abstracted from the medical record. Potential risk factors
      were analyzed, such as high grade vesicoureteral reflux at diagnosis, nadir serum
      creatinine greater than 1.0 mg/dl, urinary tract infection and severe bladder
      dysfunction requiring clean intermittent catheterization. Risk factors were
      analyzed by univariate analysis with Fisher's exact test. Those achieving
      significance were placed in a multivariate logistic regression model and an OR
      was generated. RESULTS: A total of 142 patients were identified, of whom half
      presented in the neonatal period. Of the patients 119 had sufficient records for
      evaluation and mean followup was 7.2 years. A total of 15 patients progressed to
      end stage renal disease. The mean interval from diagnosis to end stage renal
      disease was 8.1 years. Of these patients 93% initially presented with
      vesicoureteral reflux and 87% ultimately required clean intermittent
      catheterization. Increased nadir creatinine was seen in 80% of cases.
      Multivariate analysis revealed that increased nadir creatinine and bladder
      dysfunction were independent risk factors for end stage renal disease (OR 71 and
      8.9, respectively). Vesicoureteral reflux was also associated with an increased
      risk of end stage renal disease (OR 2.0), although this was not statistically
      significant. Urinary tract infections were not associated with end stage renal
      disease. CONCLUSIONS: Patients with posterior urethral valves and severe bladder
      dysfunction in whom nadir creatinine remains increased are at risk for upper
      urinary tract deterioration, requiring renal replacement therapy. It is unclear
      whether high grade vesicoureteral reflux at diagnosis may also be a poor
      prognostic sign. Further analysis is necessary to evaluate the effects of early
      aggressive bladder management on renal outcomes.

PMID- 18708226
TI  - Risk factors for recurrent ureteropelvic junction obstruction after open
      pyeloplasty in a large pediatric cohort.
AB  - PURPOSE: Recurrent ureteropelvic junction obstruction after open pyeloplasty is a
      serious complication for which treatment remains challenging. We identified risk
      factors for persistent obstruction. MATERIALS AND METHODS: We retrospectively
      reviewed the charts of 401 children who underwent open dismembered pyeloplasty
      between 1997 and 2005. Of these children 21 (5.2%) experienced recurrent
      ureteropelvic junction obstruction. Age, prenatal diagnosis, hydronephrosis
      grade, differential renal function, incision location (flank or dorsal
      lumbotomy), retrograde pyelography and stent placement were analyzed. Univariate
      and multivariate analyses were performed to identify risk factors for pyeloplasty
      failure. RESULTS: Median age at surgery was 21 months and median followup was 36
      months. Of the 401 patients dorsal lumbotomy was performed in 171 (42.6%) and a
      flank incision was used in 230 (57.4%). Retrograde pyelography was done in 195
      patients (48.6%) and stents were used in 352 (87%). Age, prenatal diagnosis,
      degree of hydronephrosis, differential renal function and stent placement did not
      have an impact on pyeloplasty outcome on univariate analysis. Recurrent
      ureteropelvic junction obstruction developed in 14 of 171 patients who had
      originally undergone dorsal lumbotomy vs 7 of 230 who had originally undergone a
      flank incision (8.1% vs 3.1%, p = 0.02) as well as in 17 of 206 who did not
      undergo initial retrograde pyelography vs 4 of 195 who did (8.3% vs 2.1%, p =
      0.005). On multivariate analysis incision type and lack of retrograde pyelography
      showed significant association with pyeloplasty failure despite adjustment for
      other risk factors (p <0.05, OR 3.2 and 4.4, respectively). CONCLUSIONS: In this
      series lack of retrograde pyelography and dorsal lumbotomy were independently
      associated with a higher risk of recurrent ureteropelvic junction obstruction.
      While retrograde pyelography or a flank approach could not be directly shown to
      prevent recurrent ureteropelvic junction obstruction, electing to perform
      retrograde pyelography may be a proxy for better perioperative planning,
      including the choice of incision, and it may ultimately increase the chances of
      successful pyeloplasty.

PMID- 18708232
TI  - Renal parenchymal damage in intermediate and high grade infantile vesicoureteral
      reflux.
AB  - PURPOSE: The association of vesicoureteral reflux, urinary tract infection and
      renal scarring is well recognized. We evaluated the incidence of renal
      parenchymal scarring in a large series of infants with primary high grade
      vesicoureteral reflux. MATERIALS AND METHODS: The medical records of 549
      consecutive infants with primary high grade vesicoureteral reflux between 1985
      and 2006 were reviewed. A total of 473 infants (86.1%) presented with febrile
      urinary tract infections, 63 (11.5%) were screened for sibling vesicoureteral
      reflux and 13 (2.4%) were investigated because of prenatally diagnosed
      hydronephrosis. Age at diagnosis was defined as patient age at the first voiding
      cystourethrogram. Renal parenchymal scarring was evaluated by dimercapto-succinic
      acid scan and classified into 3 groups, including mild--focal defects with
      between 40% and 45% relative uptake of renal radionuclide, moderate--relative
      uptake between 20% and 40%, and severe--a shrunken kidney with relative uptake
      less than 20%. RESULTS: Of the 549 infants 292 (53%) were boys and 257 (47%) were
      girls with a median age of 6 months (range 2 to 12). Reflux was unilateral in 160
      and bilateral in 389 (938 ureters). Reflux grade was II to V in 19, 372, 458 and
      89 ureters, respectively. All patients with grade II reflux had high grade reflux
      on the contralateral side. Renal parenchymal scarring was present in 122 of the
      458 infants (27%) evaluated with dimercapto-succinic scan. The incidence of renal
      parenchymal scarring was only 9% in infants without a history of urinary tract
      infection and 29% in those who presented with a urinary tract infection (p
      <0.01). Moderate to severe renal parenchymal scarring was present in 55 infants,
      of whom 73% were male and 27% were female. CONCLUSIONS: The data show that
      moderate to severe renal scarring is associated with grade IV and V reflux, and
      male sex. The incidence of renal scarring is significantly lower in infants in
      whom high grade vesicoureteral reflux is detected by screening before the
      development of urinary tract infection. Early detection may prevent urinary tract
      infection related renal parenchymal scarring.

PMID- 18708236
TI  - Self-reflections on health promotion in the UK and the USA.
AB  - OBJECTIVES: To compare and contrast the past 30-40 years of health promotion in
      the UK and the USA, and to identify two critical issues that relate to health
      promotion research and practice in both countries. METHODS: Historiography and
      self-reflection. CONCLUSIONS: Although the USA and the UK share different
      histories of health promotion development, many of the critical issues that
      characterize the field are similar. Two issues are particularly notable: the
      concern with evidence; and the problem of translation of the science of health
      promotion to practice.

PMID- 18708237
TI  - Interactions of reverse transcriptase sequences in Pol with Gag and LysRS in the
      HIV-1 tRNALys3 packaging/annealing complex.
AB  - During HIV-1 assembly, tRNA(Lys3), the primer for reverse transcriptase (RT) in
      HIV-1, is selectively packaged into the virus due to a specific interaction
      between Gag and lysyl-tRNA synthetase (LysRS). However, while Gag alone will
      incorporate LysRS, tRNA(Lys3) packaging also requires the presence of RT thumb
      domain sequences in GagPol. The formation of a tRNA(Lys3) packaging/annealing
      complex involves an interaction between Gag/GagPol/viral RNA and LysRS/tRNA(Lys),
      and herein, we have investigated whether the transfer of tRNA(Lys3) from LysRS to
      RT sequences in Pol by a currently unknown mechanism is facilitated by an
      interaction between LysRS and Pol. We demonstrate that, in addition to its
      interaction with Gag, LysRS also interacts with sequences within the
      connection/RNaseH domains in RT. However, cytoplasmic Gag/Pol interactions,
      detected by either coimmunoprecipitation or incorporation of Pol into Gag viral
      like particles, were found to be insensitive to the overexpression or
      underexpression of LysRS, indicating that a Gag/LysRS/RT interaction is not
      essential for Gag/Pol interactions. Based on this and previous work, including
      the observation that the RT connection domain is not required for tRNA(Lys3)
      packaging, but is required for tRNA(Lys3) annealing, a model is proposed for a
      tRNA(Lys3) packaging/annealing complex in which the interaction of Gag with Pol
      sequences during early viral assembly facilitates the retention in budding
      viruses of both tRNA(Lys3) and early Pol processing intermediates, with
      tRNA(Lys3) annealing to viral RNA further facilitated by the LysRS/RT
      interaction.

PMID- 18708238
TI  - Quantification of enterococci and bifidobacteria in Georgia estuaries using
      conventional and molecular methods.
AB  - Fecal pollution is a serious threat to the estuarine environment along the
      Georgia coast. Culture-dependant and molecular methodologies were utilized to
      compare and evaluate the abundance of fecal indicator bacteria in four Georgia
      estuaries (Darien River, Frederica River, Gulley Hole Creek, and St. Marys
      River). The functionality of enterococci and bifidobacteria as indicator
      organisms in marine environments was assessed, as well as Bifidobacterium
      adolescentis densities. At each study site, enterococci were enumerated as colony
      forming units (CFU) on mEI agar. For quantitative polymerase chain reaction
      (qPCR), genus- and species-specific primer sets were used to quantify
      bifidobacteria and B. adolescentis as 16S rRNA gene copies and enterococci as tuf
      gene copies. A high correlation (r=0.925) was observed between CFU and qPCR
      enumeration of enterococci. Enterococci densities in the estuarine rivers ranged
      from 3-449CFU/100ml on mEI plates and 4.58-5.39Log(10) gene copies/100ml by qPCR.
      Bifidobacteria densities ranged from 3.62-4.14Log(10) gene copies/100ml and
      suggested the Frederica River as least affected by fecal bacteria and the Darien
      River as most affected by fecal pollution. A correlation of 0.46 was observed
      among qPCR densities of enterococci and bifidobacteria at all sample sites.
      Quantitative polymerase chain reaction detection of B. adolescentis was a rapid
      (i.e., less than 2h) indicator of presumptive human fecal pollution and suggested
      that Gulley Hole Creek, the Darien River, and the St. Marys River were affected
      by fecal bacteria derived from a human source. Gulley Hole Creek and the Darien
      River had the highest levels of fecal pollution detected in the studied
      estuaries. Molecular quantification of bifidobacteria may be a more accurate
      method of determining immediate health risks associated with fecal pollution in
      estuarine water than traditional and contemporary assessments of enterococci.

PMID- 18708239
TI  - Experimental results and mathematical modelling of an autotrophic and
      heterotrophic biofilm in a sand filter treating landfill leachate and municipal
      wastewater.
AB  - A better understanding of wastewater treatment with soil filters is important to
      optimise plant operation and reduce the risk of clogging. The article presents
      results of a treatment concept which uses a combination of SBR and vertical-flow
      sand filter technology. The SBR was mainly used for denitrification and
      sedimentation of substances in particulate form. Efficient nitrification was
      achieved by the planted sand filter. Degradation rates of 10gNH(4)-N/(m(2)xd)
      were measured for periods with peak loadings. The two-dimensional dynamic model
      reproduces the biofilm growth and decay of heterotrophic and autotrophic biomass.
      It is capable of describing the clogging of the sand filter by combining a
      biochemical and a geometric model. After calibration, the model was used for the
      calculation of maximum nitrogen degradation performances. Maximum degradation
      rates of 12gNH(4)-N/(m(2)xd) can be achieved if the COD/TKN ratio is reduced
      before to a level lower than that of municipal wastewater. The COD was further
      degraded in the filter than we expected comparing it with activated sludge
      plants. Within the soil filter a biofilm thickness of up to 110microm is
      simulated depending on the embankment of gravel and grains of sand. Sensitivity
      analysis of model parameters showed the high impact of the maximum autotrophic
      growth rate, the autotrophic yield, the diffusion coefficient for oxygen and the
      number of contact points of the single grains of sand.

PMID- 18708240
TI  - Hair mercury concentrations in Korean infants could be influenced by thimerosal
      containing vaccines.

PMID- 18708241
TI  - Prostate brachytherapy after ileal pouch-anal anastomosis reconstruction.
AB  - OBJECTIVE: To determine the safety of prostate brachytherapy in patients with
      clinically localized prostate cancer who have undergone proctocolectomy with
      ileal pouch-anal anastomosis (IPAA). METHODS: We performed a retrospective chart
      review of patients with a prior history of IPAA reconstruction who underwent
      prostate brachytherapy at our institution. Clinical records were reviewed for
      demographic characteristics, postoperative dosimetry, changes in bowel function,
      and oncologic outcomes. Data were analyzed using descriptive statistics. RESULTS:
      Five patients with an IPAA underwent prostate brachytherapy for clinically
      localized prostate cancer. Mean time from colorectal reconstruction to prostate
      brachytherapy was 6.3 years. Adequate dosimetry (mean D90 114.9%, mean V100
      91.1%, mean R100 0.76 mL) was achieved in each patient. Bowel frequency worsened
      in the immediate postoperative period in all patients, but all patients returned
      to their baseline bowel pattern by 4 months after their procedure. Serious
      complications, such as J-pouch ulcers, fistulas, or fecal incontinence, did not
      occur in these patients. CONCLUSIONS: Prostate brachytherapy is a safe treatment
      option in patients with clinically localized prostate cancer and a history of
      proctocolectomy and IPAA reconstruction.

PMID- 18708242
TI  - KIT activation in uterine cervix adenosquamous carcinomas by KIT/SCF
      autocrine/paracrine stimulation loops.
AB  - OBJECTIVES: Uterine adenosquamous carcinoma (ASC) is an uncommon, yet, one of the
      most aggressive cervical cancer subtype. The successful treatment of some tumors,
      such as gastrointestinal stromal tumors (GISTs), by anti-KIT inhibitors fosters
      the study of this receptor tyrosine kinase in other malignancies. In the present
      study, we intended to molecularly characterize KIT in ASC. METHODS: In a series
      of 30 cases, we studied KIT (CD117), KIT phosphorylated/activated form, as well
      as KIT ligand, stem cell factor (SCF), by immunohistochemistry. We further
      screened for KIT hotspot mutations (exon 9, 11, 13 and 17) by PCR-SSCP and for
      KIT gene amplification by Quantitative real-time PCR in CD117 positive cases.
      RESULTS: We observed CD117 expression in approximately 13% of cases, with
      approximately 7% co-expressing SCF, which resulted in KIT
      phosphorylation/activation. No KIT activating mutations or gene amplification
      were found, despite the presence of 4q aneuploidy in one case. CONCLUSIONS: This
      is the first study assessing KIT activation and molecular alterations in a large
      series of rare ASC. Our findings showed the absence of KIT molecular alterations
      and suggested the presence of KIT activation in a small proportion of cases
      through KIT/SCF co-expression.

PMID- 18708243
TI  - Neoadjuvant chemotherapy followed by radical surgery in patients affected by
      vaginal carcinoma.
AB  - BACKGROUND: Radiotherapy represents the standard treatment for patients affected
      by FIGO stage II vaginal cancer. Several authors have suggested that neoadjuvant
      chemotherapy followed by radical surgery might be a valid treatment option in
      patients affected by cervical cancer. The objective of this study was to analyse
      the feasibility and results obtained by neoadjuvant chemotherapy followed by
      surgery in patients affected by invasive vaginal cancer with paravaginal tissue
      involvement not reaching the pelvic side wall. METHODS: Eleven patients affected
      by FIGO stage II vaginal cancer were treated with paclitaxel 175 mg/m(2) and
      cisplatin 75 mg/m(2) every 21 days for three courses followed by radical surgery.
      RESULTS: All patients were subjected to the 3 planned chemotherapy courses. Three
      (27%) patients achieved a complete clinical response and seven (64 %) patients
      achieved a partial clinical response. All patients were subjected to radical
      hysterectomy and vaginectomy. At a median follow up of 75 months two (18%)
      patients suffered a disease recurrence and one of these died of disease.
      CONCLUSIONS: Neoadjuvant chemotherapy followed by radical surgery is a feasible
      therapeutic strategy with good short- and long-term results. In women affected by
      vaginal cancer, a larger series reporting the result of this therapeutic strategy
      or the results obtained by surgery alone will aid physicians to choose the best
      therapeutic strategy for each individual patient.

PMID- 18708244
TI  - Surgical and pathologic outcomes of fertility-sparing radical abdominal
      trachelectomy for FIGO stage IB1 cervical cancer.
AB  - OBJECTIVES: To describe the surgical and pathologic findings of fertility-sparing
      radical abdominal trachelectomy using a standardized surgical technique, and
      report the rate of post-trachelectomy adjuvant therapy that results in permanent
      sterility. METHODS: A prospectively maintained database of all patients with FIGO
      stage IB1 cervical cancer admitted to the operating room for planned fertility
      sparing radical abdominal trachelectomy was analyzed. Sentinel node mapping was
      performed via cervical injection of Technetium and blue dye. RESULTS: Between
      6/2005 and 5/2008, 22 consecutive patients with FIGO stage IB1 cervical cancer
      underwent laparotomy for planned fertility-sparing radical abdominal
      trachelectomy. Median age was 33 years (range, 23-43). Histology included 13
      (59%) with adenocarcinoma and 9 (41%) with squamous carcinoma. Lymph-vascular
      invasion was seen in 9 (41%) cases. Only 3 (14%) needed immediate completion
      radical hysterectomy due to intraoperative findings (2 for positive nodes, 1 for
      positive endocervical margin). Median number of nodes evaluated was 23 (range, 11
      44); and 6 (27%) patients had positive pelvic nodes on final pathology - all
      received postoperative chemoradiation. Sixteen (73%) patients agreed to
      participate in sentinel node mapping which yielded a detection rate of 100%,
      sensitivity of 83%, specificity of 100% and false-negative rate of 17%. Eighteen
      of 19 (95%) patients who completed trachelectomy had a cerclage placed, and 9/22
      (41%) patients had no residual cervical carcinoma on final pathology. Median time
      in the operating room was 298 min (range, 180-425). Median estimated blood loss
      was 250 ml (range, 50-700), and median hospital stay was 4 days (range, 3-6). No
      recurrences were noted at the time of this report. CONCLUSIONS: Cervical
      adenocarcinoma and lymph-vascular invasion are common features of patients
      selected for radical abdominal trachelectomy. The majority of patients can
      undergo the operation successfully; however, nearly 32% of all selected cases
      will require hysterectomy or postoperative chemoradiation for oncologic reasons.
      Sentinel node mapping is useful but until lower false-negative rates are achieved
      total lymphadenectomy remains the gold standard. Investigating alternative
      fertility-sparing adjuvant therapy in node positive patients is needed.

PMID- 18708246
TI  - Student engagement and its relationship with early high school dropout.
AB  - Although the concept of school engagement figures prominently in most school
      dropout theories, there has been little empirical research conducted on its
      nature and course and, more importantly, the association with dropout.
      Information on the natural development of school engagement would greatly benefit
      those interested in preventing student alienation during adolescence. Using a
      longitudinal sample of 11,827 French-Canadian high school students, we tested
      behavioral, affective, cognitive indices of engagement both separately and as a
      global construct. We then assessed their contribution as prospective predictors
      of school dropout using factor analysis and structural equation modeling. Global
      engagement reliably predicted school dropout. Among its three specific
      dimensions, only behavioral engagement made a significant contribution in the
      prediction equation. Our findings confirm the robustness of the overall
      multidimensional construct of school engagement, which reflects both cognitive
      and psychosocial characteristics, and underscore the importance attributed to
      basic participation and compliance issues in reliably estimating risk of not
      completing basic schooling during adolescence.

PMID- 18708245
TI  - Predicting adolescent suicidality: comparing multiple informants and assessment
      techniques.
AB  - Adolescent suicidality is a serious problem among American youth. Common risk
      factors for adolescent suicidality include depression and conduct problems but
      there is little agreement on the best means to assess these factors. We compared
      multiple informants (mothers, fathers, the adolescent and a sibling) and multiple
      assessment techniques using a sample of more than 460 families. Assessment
      techniques included paper-pencil instruments, observer ratings, and diagnostic
      interviews. Suicidality was assessed concurrently and two years after the risk
      assessment. Adolescent-reported paper-pencil instruments and diagnostic
      interviews were strongly associated with concurrent and future suicidality.
      Parents' report of adolescent feelings and behaviors were also useful. Observed
      behaviors were not useful in assessing suicidality risk factors. Clinical
      recommendations include utilizing paper-pencil and diagnostic adolescent risk
      factor assessment and focusing on emotions.

PMID- 18708247
TI  - Early and middle adolescents' disclosure to parents about activities in different
      domains.
AB  - Disclosure, disclosure strategies, and justifications for nondisclosure for
      prudential, peer, multifaceted, and personal acts were assessed using a sorting
      task with 118 lower-middle class early and middle adolescents (Ms=12.77 and 15.68
      years). Adolescents were less involved in prudential than other behaviors,
      although prudential behavior was greater among middle than early adolescents;
      adolescents disclosed more about prudential and personal than multifaceted and
      peer behaviors. Nondisclosure was primarily due to concerns about parental
      disapproval (for prudential acts), claims that acts were personal or not harmful
      (for personal acts), and their mixture (for peer and multifaceted acts). When
      concerned about parental disapproval, older adolescents fully disclosed less (and
      lied somewhat more) than younger adolescents, whereas adolescents primarily
      avoided discussing the issue when they viewed acts as personal. Full disclosure
      was associated with better relationships with parents and less depressed mood;
      lying was associated with more parental behavioral control over personal issues
      and poorer relationships with fathers.

PMID- 18708248
TI  - Improved oxygen systems for childhood pneumonia: a multihospital effectiveness
      study in Papua New Guinea.
AB  - BACKGROUND: In rural hospitals of developing countries, oxygen supplies are poor
      and detection of hypoxaemia is difficult. Oxygen concentrators and pulse
      oximeters might help to manage the disease; however, use of such technology in
      developing countries needs comprehensive assessment. We studied the effect of an
      improved oxygen system on death rate in children with pneumonia in Papua New
      Guinea. METHODS: We installed an improved oxygen system in five hospitals in
      Papua New Guinea, and assessed its use in more than 11 000 children with
      pneumonia (2001-07) and compared case-fatality rates. Admissions between January,
      2001, and December, 2004, formed the pre-intervention group, and those between
      July, 2005, and October, 2007, formed the post-intervention group. Oxygen
      concentrators and pulse oximeters were introduced in the five hospitals, and a
      protocol for detection of hypoxaemia and clinical use of oxygen was supplied. All
      children admitted had their oxygen saturation measured; if it was less than 90%,
      oxygen was delivered via nasal prongs at a starting flow rate of 0.5-1 L/min. We
      recorded all costs associated with the establishment and maintenance of this
      system. The study was approved by the Medical Research Advisory Committee of
      Papua New Guinea, number MRAC 04.02. FINDINGS: Before the use of this system, 356
      of 7161 children admitted in the five hospitals for pneumonia died (case-fatality
      rate 4.97% [95% CI 4.5-5.5]), whereas 133 of 4130 children died in the 27 months
      after the introduction of the system (3.22% [2.7-3.8]). After the improved system
      was introduced, the risk of death for a child with pneumonia was 35% lower than
      was that before the project began (risk ratio 0.65 [0.52-0.78], p<0.0001).
      Mortality rates varied between hospitals. The estimated costs of this system were
      US$51 per patient treated, US$1673 per life saved, and US$50 per disability
      adjusted life-year (DALY) averted. INTERPRETATION: Pulse oximetry and oxygen
      concentrators can alleviate oxygen shortages, reduce mortality, and improve
      quality of care for children with pneumonia in developing countries. The cost
      effectiveness of this system compared favourably with that of other public-health
      interventions. FUNDING: The Papua New Guinea National Department of Health; WHO,
      Papua New Guinea and Western Pacific Regional Office; AirSep corporation,
      Buffalo, NY, USA; the Ross Trust, VIC, Australia; AusAID; Jacques Gostelli,
      Switzerland; and a grant from the University of Melbourne.

PMID- 18708249
TI  - Childhood pneumonia and oxygen treatment.

PMID- 18708250
TI  - Aqueous solution behaviour and membrane disruptive activity of pH-responsive
      PEGylated pseudo-peptides and their intracellular distribution.
AB  - The effect of PEGylation on the aqueous solution properties and cell membrane
      disruptive activity of a pH-responsive pseudo-peptide, poly(l-lysine iso
      phthalamide), has been investigated by dynamic light scattering, haemolysis and
      lactate dehydrogenase (LDH) assays. Intracellular trafficking of the polymers has
      been examined using confocal and fluorescence microscopy. With increasing degree
      of PEGylation, the modified polymers can form stabilised compact structures with
      reduced mean hydrodynamic diameters. Poly(l-lysine iso-phthalamide) with a low
      degree of PEGylation (17.4 wt%) retained pH-dependent solution behaviour and
      showed enhanced kinetic membrane disruptive activity compared to the parent
      polymer. It facilitated trafficking of endocytosed materials into the cytoplasm
      of HeLa cells. At levels of PEGylation in excess of 25.6 wt%, the modified
      polymers displayed a single particle size distribution unresponsive to pH, as
      well as a decrease in cell membrane lytic ability. The mechanism involved in
      membrane destabilisation was also investigated, and the potential applications of
      these modified polymers in drug delivery were discussed.

PMID- 18708251
TI  - Development of a chitosan-based wound dressing with improved hemostatic and
      antimicrobial properties.
AB  - Hemorrhage remains a leading cause of early death after trauma, and infectious
      complications in combat wounds continue to challenge caregivers. Although
      chitosan dressings have been developed to address these problems, they are not
      always effective in controlling bleeding or killing bacteria. We aimed to refine
      the chitosan dressing by incorporating a procoagulant (polyphosphate) and an
      antimicrobial (silver). Chitosan containing different amounts and types of
      polyphosphate polymers was fabricated, and their hemostatic efficacies evaluated
      in vitro. The optimal chitosan-polyphosphate formulation (ChiPP) accelerated
      blood clotting (p = 0.011), increased platelet adhesion (p=0.002), generated
      thrombin faster (p = 0.002), and absorbed more blood than chitosan (p < 0.001).
      Silver-loaded ChiPP exhibited significantly greater bactericidal activity than
      ChiPP in vitro, achieving a complete kill of Pseudomonas aeruginosa and a >
      99.99% kill of Staphylococcus aureus consistently. The silver dressing also
      significantly reduced mortality from 90% to 14.3% in a P. aeruginosa wound
      infection model in mice. Although the dressing exerted severe cytotoxicity
      against cultured fibroblasts, wound healing was not inhibited. This study
      demonstrated for the first time, the application of polyphosphate as a hemostatic
      adjuvant, and developed a new chitosan-based composite with potent hemostatic and
      antimicrobial properties.

PMID- 18708252
TI  - Strength and fluoride release characteristics of a calcium fluoride based dental
      nanocomposite.
AB  - Secondary caries and restoration fracture remain the two most common problems in
      restorative dentistry. Release of fluoride ions (F) could be a substantial
      benefit because F could enrich neighboring enamel or dentin to combat caries. The
      objective of this study was to incorporate novel CaF(2) nanoparticles into dental
      resin to develop stress-bearing, F-releasing nanocomposite. CaF(2) nanoparticles,
      prepared in our laboratories for the first time, were combined with reinforcing
      whisker fillers in a resin. Flexural strength (mean+/-sd; n=6) was 110+/-11 MPa
      for the composite containing 30% CaF(2) and 35% whiskers by mass. It matched the
      108+/-19 MPa of a stress-bearing, non-releasing commercial composite (Tukey's at
      0.05). The composite containing 20% CaF(2) had a cumulative F release of 2.34+/
      0.26 mmol/L at 10 weeks. The initial F release rate was 2 microg/(hcm(2)), and
      the sustained release rate after 10 weeks was 0.29 microg/(hcm(2)). These values
      exceeded the reported releases of traditional and resin-modified glass ionomer
      materials. In summary, nanocomposites were developed with relatively high
      strength as well as sustained release of fluoride ions, a combination not
      available in current materials. These strong and F-releasing composites may yield
      restorations that can reduce the occurrence of both secondary caries and
      restoration fracture.

PMID- 18708254
TI  - Preservation and postponement of female fertility.
AB  - In the last several decades, both the growing number of reproductive age cancer
      survivors, and the trend of women from western countries delaying child-bearing
      to a later age have been markedly increasing. The confluence of these two
      epidemiologic trends has led to the need for better and more widely available
      strategies for fertility preservation. In this paper, we will first review both
      the established and experimental methodologies which can be utilized for either
      the preservation or postponement of female fertility. These options currently
      include embryo and oocyte cryopreservation, cortical and whole ovary
      cryopreservation, ovarian transplantation, ovarian transposition, and
      gonadotropin releasing hormone agonist protection. As laboratory and surgical
      techniques for oocyte and ovary cryopreservation continue to improve, modalities
      now considered experimental will become part of routine practice for reproductive
      medicine specialists.

PMID- 18708253
TI  - Barium, TEA and sodium sensitive potassium channels are present in the human
      placental syncytiotrophoblast apical membrane.
AB  - The human placental syncytiotrophoblast (hSTB) is a polarized epithelial
      structure, without paracellular routes, forming the main barrier for materno
      fetal exchange. There is ample evidence suggesting the presence of potassium
      (K(+)) channels in the placental apical membrane; which could contribute to
      membrane potential and volume regulation. We have therefore examined the K(+)
      currents of isolated apical membranes from human term placenta using
      electrophysiological methods: reconstitution of ion channels from apical
      membranes into giant liposomes (single channel recordings, patch clamp method) or
      their functional transplantation into Xenopus laevis oocytes (total currents
      recording, voltage clamp method). Single channel recording experiments show the
      presence of K(+) channels in the hSTB microvillous membrane sensitive to
      Tetraethylammonium (TEA) and Barium (Ba(+2)). Patch current activity was
      diminished 50% and 70% by 20 mmol/L TEA and 5 mmol/L Ba(+2) respectively. The
      more frequent conductance was approximately 73pS, however several levels of
      current were detected suggesting the presence of more than one type of K(+)
      channel. In addition, sodium (Na(+)) sensitivity was detected in the patch
      current thus, over 10 mmol/L Na(+) reduced the seal current to 38%. These results
      were corroborated by the total current experiments where the K(+) current
      elicited in injected oocytes with apical purified membrane was blocked by Ba(+2)
      and TEA. The total current was also affected by Na(+), becoming larger when a
      Na(+)-free solution was used. Our results show the existence of at least two
      types of Ba(+2)-sensitive K(+) channels including a TEA sensitive sub-population,
      and some of them Na(+) sensitive K(+) channels. These channels could be the
      conductive pathways proposed previously for this cation in placental hSTB. Our
      novel contribution has been to successfully obtain K(+) channel recordings in
      systems suitable for electrophysiological studies of isolated apical membranes.

PMID- 18708255
TI  - Polymorphisms in the vascular endothelial growth factor gene and risk of age
      related macular degeneration: the Rotterdam Study.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is an important regulator of
      angiogenesis and a target for inhibition therapy in wet age-related macular
      degeneration (AMD). The purpose of this study was to examine whether genetic
      variation in the VEGF gene is associated with AMD and, especially, with its wet
      end stage. DESIGN: Prospective population-based cohort study. PARTICIPANTS: Four
      thousand two hundred twenty-eight participants aged 55 years and older. METHODS:
      AMD was classified according to a modified International Classification System
      using fundus color images. Genotypes and haplotypes were determined for 3
      functional VEGF single nucleotide polymorphisms (SNPs): C-2578A, G-1154A, and G
      634C. Cox proportional hazards regression analyses were used to investigate
      possible associations between the individual SNPs and incident AMD. The
      Haplo.Stats program was used to test the associations between VEGF gene
      haplotypes and incident AMD. MAIN OUTCOME MEASURE: AMD RESULTS: Of 4228
      participants at risk for incident early and late AMD for whom blood specimens
      were available for VEGF genotyping, incident early AMD developed in 514 and
      incident late AMD developed in 89 (35 dry and 54 wet) after a mean follow-up of
      7.4 years. None of the SNPs showed a significant association with incident early
      or late AMD, especially not with incident wet AMD. Haplotype analyses also
      detected no associations. CONCLUSIONS: The a priori hypothesis that 3 common SNPs
      in the VEGF gene would be a risk factor for AMD, especially the wet form, could
      not be confirmed.

PMID- 18708256
TI  - Measurement of Goldmann applanation tonometer calibration error.
AB  - OBJECTIVE: To determine the frequency and possible origins of calibration errors
      of the Goldmann applanation tonometer and to investigate intraobserver and
      interobserver agreement in the measurement of such calibration errors. DESIGN:
      Evaluation of diagnostic test or technology. PARTICIPANTS: One hundred thirty-two
      slit-lamp-mounted Haag-Streit Goldmann tonometers (Model AT 900 C/M; Haag-Streit,
      Bern, Switzerland). METHODS: Calibration error testing was performed using the
      standard calibration error check weight bar. A single observer tested 25
      instruments on 2 consecutive days. Two observers independently measured
      calibration errors of another 40 instruments. A single observer performed
      prospective testing of the remaining Haag-Streit Goldmann tonometers, 6 months
      after their annual calibration by the bioengineering department of the hospital.
      Four months later, the same observer retested the instruments that were found to
      be faulty earlier. MAIN OUTCOME MEASURE: Goldmann applanation tonometer
      calibration error. RESULTS: Only 4% of Goldmann tonometers were found to be
      within the manufacturer's recommended calibration error tolerance (+/-0.5 mmHg)
      at 20 mmHg. Twenty-eight percent of instruments had calibration errors of more
      than +/-2 mmHg at the 20-mmHg testing level. An additional 12.12% had calibration
      errors of more than +/-2 mmHg at the 0- or 60-mmHg testing levels, or both. Four
      months after the initial testing and repair of the 53 faulty instruments, 20.75%
      again were found to have calibration errors of more than +/-2 mmHg at any one or
      more testing level(s). Intraclass correlation coefficients for intraobserver
      agreement at 20 mmHg were 0.57 (95% confidence interval [CI], 0.25-0.78) for
      positive error, 0.82 (95% CI, 0.65-0.92) for negative error, and for
      interobserver agreement at 20 mmHg, 0.83 (95% CI, 0.70-0.90) for positive error
      and 0.83 (95% CI, 0.70-0.90) for negative error. CONCLUSIONS: The authors found
      good agreement in measurement of Goldmann applanation tonometer calibration
      error. A significant number of instruments had clinically unacceptable
      calibration errors. A more frequent calibration error testing and automation of
      calibration error check is desirable. FINANCIAL DISCLOSURE(S): The authors have
      no proprietary or commercial interest in any materials discussed in this article.

PMID- 18708257
TI  - The utility of symptoms in identification of primary angle-closure in a high-risk
      population.
AB  - OBJECTIVE: To examine the frequency of symptoms associated with primary angle
      closure in an East Asian population with high rates of disease. DESIGN:
      Population-based survey. PARTICIPANTS: One thousand adults from rural and urban
      provinces of Mongolia were examined. METHODS: A standard questionnaire was used
      to determine a history of symptoms of angle closure. All participants underwent
      applanation tonometry, gonioscopy, and slit-lamp examination by the same
      observer. The frequency of symptoms was compared between normal subjects and
      those in 3 high-risk or affected groups: gonioscopically confirmed occludable
      angles, peripheral anterior synechiae (PAS) detected on gonioscopy, and anterior
      chamber depth of less than 2.5 mm. MAIN OUTCOME MEASURES: The frequency of
      symptoms associated with primary angle closure. RESULTS: Symptoms of visual
      disturbance and ocular pain traditionally linked with angle closure were reported
      frequently by both normal and potentially affected people. Intermittent blurring
      of vision at night was the only common symptom of angle closure that was
      significantly more frequent in people with narrow angles and PAS (P = 0.004,
      48.4% vs. 31.0% narrow angles; P = 0.001, 54.3% vs. 30.6% PAS), but not in those
      with shallow anterior chambers (P = 0.670, 38.3% vs. 30.9%). CONCLUSIONS: Direct
      questioning about symptoms associated with angle closure identified high rates of
      positive responses in both affected and unaffected groups. Although the rate of
      symptoms tended to be higher in affected people, none of these symptoms were
      specific enough to be considered useful as a diagnostic criterion.

PMID- 18708258
TI  - Ranibizumab for the treatment of macular edema associated with perfused central
      retinal vein occlusions.
AB  - PURPOSE: Assessment of biological effect, visual acuity changes, and safety of
      intravitreal (IVT) ranibizumab in patients with macular edema associated with
      perfused central retinal vein occlusion (CRVO). DESIGN: Ongoing, prospective,
      open-label, single-center, uncontrolled study. PARTICIPANTS: Ten adult patients
      with macular edema associated with perfused CRVO. METHODS: Patients were randomly
      assigned to receive 3 monthly IVT injections of either 0.3 or 0.5 mg ranibizumab
      (n = 5 at each dose). Additional injections were administered quarterly as needed
      over the ensuing 21 months at the physician's discretion for recurrent or
      persistent macular edema. MAIN OUTCOME MEASURES: The predetermined primary
      endpoint was the percentage of patients gaining >or=15 letters of best-corrected
      Early Treatment of Diabetic Retinopathy Study visual acuity (BCVA). The secondary
      endpoints include the mean change in BCVA and central retinal thickness (CRT)
      measured by optical coherence tomography, the rate of progression to ischemic
      CRVO, extent of intraocular hemorrhage, retinal vein diameter, optic nerve head
      swelling, and the incidence and severity of ocular and nonocular adverse events.
      RESULTS: After 3, 6, and 9 months of follow-up, 40%, 10%, and 30% of patients,
      respectively, gained >or=15 letters in BCVA; mean BCVA improved by 12+/-20
      letters, 3+/-21 letters, and 1+/-24 letters, respectively, compared with
      baseline; CRT showed a mean decrease of 272+/-244 microm, 88+/-178 microm, and
      119+/-153 microm, compared with baseline. No significant differences were
      observed between the 0.3- and 0.5-mg doses. Most patients experienced decreases
      in the extent of retinal hemorrhage, retinal vein diameter, and optic nerve head
      swelling at months 3 and 6 compared with baseline. No patients progressed to
      ischemic CRVO or experienced a severe adverse event that was attributed to
      ranibizumab. CONCLUSIONS: Ranibizumab is generally well-tolerated and may improve
      BCVA and decrease CRT. The improvements in BCVA and CRT observed during the
      initial monthly injection period (0 to 3 months) were possibly lost to the
      recurrence of macular edema in between ranibizumab injection during the quarterly
      treatments (3 to 9 months). The extent of retinal hemorrhage, retinal vein
      diameter, and nerve swelling continued to normalize for most of the patients from
      baseline to 6 months. Follow-up is ongoing, and alternative dosing regimens are
      being evaluated.

PMID- 18708259
TI  - Prevalence of dry eye disease among Japanese visual display terminal users.
AB  - OBJECTIVE: To determine the prevalence of dry eye disease (DED) and risk factors
      among young and middle-aged Japanese office workers using visual display
      terminals (VDTs). DESIGN: Cross-sectional prevalence survey. PARTICIPANTS: Four
      thousand three hundred ninety-three Japanese young and middle-aged office workers
      using VDTs. INTERVENTION: Office workers completed questionnaires sent by e-mail
      designed to detect dry eye diagnosis and risk factors. MAIN OUTCOME MEASURES:
      Clinically diagnosed DED was defined as the presence of a previous clinical
      diagnosis of DED by dry eye specialists or severe symptoms of DED (both dryness
      and irritation constantly or often). Current symptoms of DED and possible risk
      factors such as age, duration of VDT use, type of VDT work, environmental
      factors, presence of systemic diseases, systemic medicine use, smoking history,
      and contact lens (CL) use were the main outcome measures. We used logistic
      regression to examine associations between DED and other demographic factors.
      RESULTS: Of the 4393 office workers, 3549 (80.1%) completed the questionnaire.
      Clinically diagnosed DED was present in 266 (10.1%) of 2640 male subjects and in
      195 (21.5%) of 909 female subjects. Severe symptoms of DED were observed in 711
      male and in 436 female participants. More than 4 hours of VDT use was associated
      with an increased risk of DED (odds ratio [OR], 1.68; 95% confidence interval
      [CI], 1.40-2.02). In addition, CL use (OR, 3.91; 95% CI, 3.37-4.53) increased the
      risk of severe dry eye symptoms. CONCLUSIONS: Dry eye disease leading to a
      clinical diagnosis or severe symptoms is prevalent among young and middle-aged
      Japanese office workers. The condition is more prevalent among females, CL
      wearers, and prolonged VDT users. Relevant measures directed against the
      modifiable risks could provide a positive impact on public health and quality of
      life of office workers. FINANCIAL DISCLOSURE(S): The authors have no proprietary
      or commercial interest in any materials discussed in this article.

PMID- 18708260
TI  - Comparison of one-day versus one-hour application of topical gatifloxacin in
      eliminating conjunctival bacterial flora.
AB  - PURPOSE: To compare efficacies of 1-day, 1-hour, and combined 1-day/1-hour
      preoperative topical gatifloxacin in eliminating conjunctival bacterial flora.
      DESIGN: Prospective, comparative case series. PARTICIPANTS: Sixty patients (120
      eyes) scheduled to undergo anterior segment intraocular surgery at Stanford
      University Medical Center. METHODS: Cultures were collected from the palpebral
      conjunctival sac at baseline and after 1 day (4 doses), 1 hour (3 doses), and 1
      day/1 hour (7 doses) of gatifloxacin use. MAIN OUTCOME MEASURES: Incidence of
      positive bacterial samples collected pre- and post-antibiotic treatment and
      number of colony forming units (CFUs). RESULTS: SeptiChek (Becton Dickinson,
      Franklin Lakes, NJ) positive cultures significantly decreased from 67% growth at
      baseline to 28% (P<0.0001) after 1 day and from 60% at baseline to 37% (P =
      0.018) after 1 hour of gatifloxacin use. Reductions of 44% growth at baseline to
      12% (P = 0.0001) after 1 day and 32% at baseline to 13% (P = 0.029) after 1 hour
      of gatifloxacin use were observed on blood agar. Surgical eyes that received both
      1-day and 1-hour preoperative gatifloxacin had reductions from 67% growth at
      baseline to 18% posttreatment (P<0.0001) and 45% at baseline to 7% posttreatment
      (P<0.0001) on SeptiChek and blood agar media, respectively. In addition to a
      lower frequency of positive cultures, a significantly lower CFU count was found
      after 1-day (P = 0.004) and 1-hour (P = 0.049) gatifloxacin use compared with
      pretreatment levels. Combined 1-day/1-hour doses of gatifloxacin were associated
      with a greater reduction in CFUs (P = 0.001) when compared with 1-hour treatment
      alone. CONCLUSIONS: Both 1-hour and 1-day topical gatifloxacin use are effective
      in reducing the frequency of conjunctival bacterial growth and the overall
      bacterial load as measured by CFUs, relative to baseline. Although a 1-hour
      pretreatment is associated with a reduction in bacterial growth, the combination
      of 1-day and 1-hour preoperative gatifloxacin dosing results in an even lower
      overall bacterial load, suggesting that the latter might be the preferred
      preoperative regimen for eyes undergoing anterior segment surgery.

PMID- 18708261
TI  - Vitreous levels of bevacizumab and vascular endothelial growth factor-A in
      patients with choroidal neovascularization.
AB  - PURPOSE: To investigate the vitreous levels of bevacizumab and vascular
      endothelial growth factor-A (VEGF-A) after intravitreal injection of the drug in
      patients with choroidal neovascularization (CNV). DESIGN: Interventional case
      series. PARTICIPANTS: Eleven eyes of 11 patients with submacular hemorrhage and
      CNV due to age-related macular degeneration (n = 10) or angioid streaks (n = 1).
      METHODS: All patients were treatment naive except for a single dose of
      intravitreal injection of bevacizumab (1.25 mg/50 muL dose) and subsequent
      vitrectomy after various intervals (1-101 days) because of active and progressive
      lesion. Intravitreal free bevacizumab and VEGF-A levels were measured using
      enzyme-linked immunosorbent assay and microsphere-based immunoassay,
      respectively. Vitreous VEGF-A isoforms were analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and Western blotting. MAIN OUTCOME MEASURES:
      Intravitreal bevacizumab and VEGF-A levels were measured and pharmacokinetic
      parameters were calculated. RESULTS: Pharmacokinetics of intravitreal bevacizumab
      followed a 2-compartment model with initial and terminal half-lives of 0.5 and
      6.7 days, respectively. Bevacizumab could be detected in all cases, ranging from
      2.63 ng/ml to 165 microg/ml. The peak concentration was observed on the second
      day after intravitreal bevacizumab injection. Vitreous free VEGF-A levels ranged
      from 0.2 to 33.9 pg/ml and showed a negative correlation with the bevacizumab
      concentration (P<0.001; r = -0.955) and a positive correlation with time
      (P<0.001; r = 0.964). However, the percentage expression of VEGF-A(165) exhibited
      a positive correlation with the bevacizumab concentration (P = 0.032, r = 0.645)
      and a negative correlation with time (P = 0.007, r = -0.755). A time-dependent
      increase was found for the percentage expression of VEGF-A(189) (P = 0.023, r =
      0.673). Neither bevacizumab- nor time-related alterations were found for VEGF
      A(121). CONCLUSIONS: Based on pharmacokinetics, the interval of 6-7 weeks would
      be appropriate for efficacy, although clinical trials should guide dosing
      recommendations. Vitreous levels of free VEGF-A showed a negative correlation
      with the bevacizumab concentration, which confirmed the in vivo binding affinity
      of bevacizumab to VEGF-A. The analysis of the VEGF-A isoforms suggests
      differences of interaction between bevacizumab and individual VEGF-A isoforms.

PMID- 18708262
TI  - Successful treatment of post-neurosurgical intracranial Mycoplasma hominis
      infection using gatifloxacin.
AB  - We describe two cases of intracerebral infection with Mycoplasma hominis
      following neurosurgery, the first after removal of a colloid cyst, the other
      after a craniotomy following a motor vehicle accident (MVA). Both infections were
      successfully treated with parenteral gatifloxacin, with ongoing clindamycin or
      moxifloxacin for associated osteomyelitis.

PMID- 18708263
TI  - The functional impact of subsyndromal depressive symptoms in bipolar disorder:
      data from STEP-BD.
AB  - BACKGROUND: This report describes baseline characteristics and functional
      outcomes of subjects who have prospectively observed subsyndromal symptoms after
      a major depressive episode (MDE). METHODS: All subjects were participants in the
      Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). We
      identified subjects with at least 2 years of observation whose prior or current
      episode was a MDE, and who were in a stable clinical state of either recovered
      (no more than 2 moderate symptoms for at least 8 weeks), a MDE by DSM-IV
      criteria, or with continued subsyndromal symptoms. The subsyndromal group was
      defined a priori as 3 or more moderate affective symptoms but without meeting
      diagnostic criteria for major depression. RESULTS: The final cohort included 1094
      recovered, 112 subsyndromal, and 310 individuals in a MDE. The average time spent
      in each clinical status ranged from 120 to 132 days. The subsyndromal group was
      most similar to those in a MDE, differing only on the intensity of depressive
      symptoms and the number of work days missed due to ongoing symptoms. Reported
      sadness, inability to feel and lassitude were each associated with multiple
      measures of impairment. LIMITATIONS: This study is limited by the cross-sectional
      approach to defining outcomes. CONCLUSIONS: These findings are consistent with
      studies in unipolar major depression that indicate that functional impairment
      observed in the context of subsyndromal depressive symptoms is comparable to that
      of a full episode. This work underscores the need to include subsyndromal
      symptoms in study outcomes and to target full remission in clinical practice.

PMID- 18708264
TI  - CSF and plasma cytokines at delivery and postpartum mood disturbances.
AB  - BACKGROUND: Immune activation has been shown to be involved in the
      pathophysiology of anxiety states and major depression and pregnancy is
      associated with a characteristic immune activation to sustain the fetus. Despite
      the possibility of a relation between immune parameters and postpartum mood
      disturbance, few studies have explored this association. Further, no study to
      date has examined CSF. METHODS: Fifty-six Greek parturients were recruited and a
      detailed medical and obstetric history was recorded. All of them completed the
      Postpartum Blues Questionnaire (on admission and on days 1-4 postpartum) and the
      Edinburgh Postnatal Depression Scale (at first and sixth week postpartum). At
      delivery, a blood sample and a CSF sample while puncturing for epidural analgesia
      were taken from 33 participants; blood samples only were obtained from the rest
      of the 23 parturients. TNF-a and IL-6 were quantified with an ELISA assay.
      RESULTS: A multiple regression analysis of psychometric scores depending on
      cytokine levels revealed that cytokine levels were positively associated with
      depressive mood during the first four days postpartum (p=0.035 for CSF IL-6,
      p=0.025 for CSF TnF-a, p=0.023 for serum TnF-a) and also at sixth week postpartum
      (p=0.012 for CSF IL-6, p=0.072 for CSF TnF-a). Pregnancy duration had an adverse
      association to psychometric scores. CONCLUSIONS: It is suggested that immune
      mechanisms may play a role in the etiopathology of postpartum depressive mood
      shifts. The role of a "rebound" reaction of the maternal immune system postnatal
      should be further investigated.

PMID- 18708265
TI  - A 5-year longitudinal study of the relationships between stress, coping, and
      immune cell beta(2)-adrenergic receptor sensitivity.
AB  - Caring for a spouse with Alzheimer's disease (AD) is associated with overall
      health decline and impaired cardiovascular functioning. This morbidity may be
      related to the effects of caregiving stress and impaired coping on beta(2)
      adrenergic receptors, which mediate hemodynamic and vascular responses and are
      important for peripheral blood mononuclear cell (PBMC) trafficking and cytokine
      production. This study investigated the longitudinal relationship between stress,
      personal mastery, and beta(2)-adrenergic receptor sensitivity assessed in vitro
      on PBMC. Over a 5-year study, 115 spousal AD caregivers completed annual
      assessments of caregiving stress, mastery, and PBMC beta(2)-adrenergic receptor
      sensitivity, as assessed by in vitro isoproterenol stimulation. Heightened
      caregiving stress was associated with significantly decreased receptor
      sensitivity, whereas greater sense of personal mastery was associated with
      significantly increased receptor sensitivity. These results suggest that
      increased stress may be associated with a desensitization of beta(2)-receptors,
      which may contribute to the development of illness among caregivers. However,
      increased mastery is associated with increased receptor sensitivity, and may
      therefore serve as a resource factor for improved health in this population.

PMID- 18708266
TI  - Predictors of occupational status six months after hospitalization in persons
      with a recent onset of psychosis.
AB  - Participation in work or school activity is an important aspect of social
      functioning in individuals with a recent onset of psychosis. We measured the
      predictors of occupational status 6 months following hospitalization in a sample
      of 71 adults with recent onset affective or non-affective psychosis. At baseline,
      participants were evaluated with cognitive measures including the Wisconsin Card
      Sorting Test, symptom rating scales, the Modified Vocational Index to assess
      occupational status, and other clinical and demographic measures. At follow-up,
      occupational status was re-assessed and categorized as whether or not the patient
      had any current work or school activity. Results of a backwards stepwise logistic
      regression examining occupational status at follow-up yielded a significant model
      with the following independent predictors: a higher baseline level of cognitive
      functioning as measured by performance on the Wisconsin Card Sorting Test lower
      level of baseline depression as measured by the Calgary Depression Scale; and
      better socioeconomic status as measured by level of maternal education. Cognitive
      functioning, but not psychosis severity, is a significant independent predictor
      of occupational status early in the course of psychotic illness.

PMID- 18708267
TI  - Emotional state and dreams in pregnant women.
AB  - The aim of this study was to investigate the frequency of recall and the content
      of dreams during pregnancy, as well as their correlation with socio-demographic,
      obstetric and physician-patients relationship variables, emotional state and
      duration of labour. A questionnaire, designed to analyse background
      characteristics, was given to 290 women in the third trimester of gestation. The
      psychiatric analysis of anxiety and depression was performed using the Hamilton
      Rating Scale for Anxiety and the Montgomery-Asberg Depression Rating Scale, while
      dreams were divided into masochistic and pleasant according to Beck's criteria.
      Oneiric activity was found to be associated with age >or= 35 years, higher family
      income, higher educational level, and a "satisfactory" physician-patient
      relationship. Masochistic content was associated with age<35 years, quality of
      information and frequent thoughts of delivery. Concerning the emotional state,
      depression levels were higher in women reporting masochistic dreams, while no
      difference in anxiety levels was found. Labour duration was shorter in the
      dreamer group and in patients with masochistic dream content. These findings may
      indicate that, also in pregnancy, the number and the content of dreams are
      influenced by women's mood and that the evaluation of the oneiric activity might
      represent a useful tool for clinicians either to investigate the women's
      emotional state or to predict its repercussions on the course of labour.

PMID- 18708269
TI  - The congenital myasthenic syndromes.
AB  - The congenital myasthenic syndromes (CMS) are rare inherited disorders of
      neuromuscular transmission characterised by fatigable muscle weakness. Thus far,
      genetic analysis has identified mutations in eleven different genes but it is
      clear that additional phenotypic subgroups exist where the underlying genetics
      has not yet been defined. Although each syndrome results from defective synaptic
      transmission at the neuromuscular junction, the patients show a variable set of
      phenotypes. Here, we provide a brief clinical review.

PMID- 18708268
TI  - Innate immune dysfunction in the neonatal rat following prenatal endotoxin
      exposure.
AB  - The efficacy of the neonatal innate immune system to respond to bacterial
      exposure following maternal infection is of great interest, as the neonatal
      period is one of relative immune immaturity, and is associated with high rates of
      morbidity and mortality. This study aimed to determine the response to an in-vivo
      endotoxin challenge in the neonatal period following prenatal exposure to
      bacterial endotoxin. Pregnant Fischer 344 dams received either endotoxin or the
      vehicle on gestational days 16, 18 and 20 (term=23 days). The neonatal (5 day)
      offspring were then exposed to an endotoxin challenge; blood was collected at
      baseline or at 4 h for analysis of blood cell counts, corticosterone, TNF alpha
      and IL-1 beta, levels. The neonatal rat pups responded to the challenge with
      significantly reduced corticosterone, TNF alpha and IL-1 beta levels compared to
      controls (p<0.003). Monocyte, neutrophil and eosinophil counts were also
      significantly reduced in the prenatal endotoxin offspring compared to controls
      (p<0.02). While the immune system is functionally immature in the neonatal
      period, these results suggest that prenatal infection may further reduce the
      capacity of the innate neonatal immune system to respond to endotoxin, leaving
      offspring more vulnerable to pathogenic invasion in neonatal life.

PMID- 18708270
TI  - Isolated interrupted aortic arch: in a 40-year-old adult.
AB  - Interrupted aortic arch (IAA) is a scarce and generally lethal congenital
      malformation. Patients with complete IAA scarcely reach adult age without
      previous surgical intervention. In this case, we presented a 40-year-old isolated
      IAA case with hypertension and angina pectoris. IAA just distal to left
      subclavian artery and markedly developed collateral circulation was demonstrated
      via cardiac catheterization (CC) and multi-slice computed tomography angiography
      (MSCT).

PMID- 18708271
TI  - Accuracy of two scores in the diagnosis of stroke subtype in a multicenter cohort
      study.
AB  - STUDY OBJECTIVE: The distinction between hemorrhagic and ischemic stroke has
      critical implications for management. For that purpose, clinical scores have been
      proposed to be used in areas with limited health care resources where brain
      computed tomographic (CT) scan is not readily available. We conducted this study
      to evaluate the predictive value of the Allen and Siriraj scores in the
      differential diagnosis of stroke subtypes. METHODS: We prospectively collected
      data for 4 years on the clinical characteristics of patients with stroke in a
      multicenter study. For all patients, we calculated the Allen and the Siriraj
      scores and we assessed their accuracy in predicting stroke subtypes with receiver
      operating characteristics (ROC) curves. RESULTS: We assessed 1,023 patients. Of
      these, 82.7% (n=846) had ischemic stroke. The area under the ROC curve was higher
      for Siriraj score compared with the Allen score (0.780 versus 0.702; P=.04).
      Using the original cutoff points, Siriraj score has a sensitivity for the
      diagnosis of hemorrhage of 60% and a specificity of 95%; the corresponding values
      for the Allen score are 55% and 70%, respectively. The negative predictive value
      was higher for Siriraj score compared to the Allen score (90% versus 80%). The
      diagnosis of stroke subtype was best predicted at Siriraj score less than -4.
      CONCLUSION: Siriraj score is a valid and useful tool for predicting stroke
      subtype in a clinical setting in which financial constraints make systematic
      brain CT scan unfeasible.

PMID- 18708272
TI  - 2,3-Disubstituted-1,4-naphthoquinones, 12H-benzo[b]phenothiazine-6,11-diones and
      related compounds: synthesis and biological evaluation as potential
      antiproliferative and antifungal agents.
AB  - A series of 2-chloro-3-arylsulfanyl-[1,4]naphthoquinones (2), 2,3-bis
      arylsulfanyl-[1,4]naphthoquinones (3) and 12H-benzo[b]phenothiazine-6,11-diones
      and their analogs 6-8 were synthesized and evaluated for their antiproliferative
      activity against human cervical cancer (HeLa) cells. Compounds 3a and 3b were
      found to possess most potent antiproliferative and cell killing ability.
      Compounds 1-8 were also evaluated for antifungal activities. The structure
      activity relationship of these compounds was studied and the results show that
      compound 2a (MIC(50)=1.56 microg/mL) exhibited in vitro potent antifungal
      activity compared to the clinically useful antifungal drug Fluconazole
      (MIC(50)=2.0 microg/mL) against Sporothrix. schenckii. Compound 2a (MIC(50)=1.56
      microg/mL) also exhibited same antifungal activity compared to clinically useful
      drug Amphotericin-B (MIC(50)=1.56 microg/mL) against Trichophyton.
      mentagraphytes.

PMID- 18708273
TI  - Synthesis, characterization and antibacterial activity of some triazole Mannich
      bases carrying diphenylsulfone moieties.
AB  - A series of Mannich bases of 4-substituted 5-[4-(4-X-phenylsulfonyl)phenyl]-2,4
      dihydro-3H-1,2,4-triazole-3-thiones, X=H, Cl, Br, 3 and 5 were synthesized and
      characterized on the basis of IR, NMR and elemental analyses. The potential
      antibacterial effects of the synthesized compounds were investigated using the
      Acinetobacter baumanii ATCC 19606; Citrobacter freundii ATCC 8090; Pseudomonas
      aeruginosa ATCC 9027; Enterococcus faecalis ATCC 19433; Staphylococcus aureus
      ATCC 12600; Staphylococcus epidermidis ATCC 14990; Bacillus subtilis ATCC 6633
      strains. Some of them exhibited promising activities against A. baumanii and B.
      subtilis.

PMID- 18708274
TI  - A meta-analytic review of the relationships between the five-factor model and DSM
      IV-TR personality disorders: a facet level analysis.
AB  - Theory and research have suggested that the personality disorders contained
      within the American Psychiatric Association's Diagnostic and Statistical Manual
      of Mental Disorders (DSM-IV-TR) can be understood as maladaptive variants of the
      personality traits included within the five-factor model (FFM). The current meta
      analysis of FFM personality disorder research both replicated and extended the
      2004 work of Saulsman and Page (The five-factor model and personality disorder
      empirical literature: A meta-analytic review. Clinical Psychology Review, 23,
      1055-1085) through a facet level analysis that provides a more specific and
      nuanced description of each DSM-IV-TR personality disorder. The empirical FFM
      profiles generated for each personality disorder were generally congruent at the
      facet level with hypothesized FFM translations of the DSM-IV-TR personality
      disorders. However, notable exceptions to the hypotheses did occur and even some
      findings that were consistent with FFM theory could be said to be instrument
      specific.

PMID- 18708275
TI  - Widening health inequalities among U.S. military retirees since 1974.
AB  - I explore trends in mortality among U.S. military retirees using a new dataset of
      payroll records that include pay grade. Trends in mortality by pay grade reveal
      that health inequalities steadily widened between 1974 and 2004. Additive
      differentials in mortality rates remained stable, but since mortality declined
      exponentially, by a factor of about one third, proportional differentials in
      mortality and thus additive differentials in life expectancy have widened. The
      advantage in life expectancy enjoyed by retired officers grew roughly from 3 to 4
      years. The sources of these trends remain unclear and are beyond the ability of
      the data to inform, but the results bear implications for trends in inequality
      and for policy.

PMID- 18708277
TI  - A theoretical study of repeating sequence in HRP II: a combination of molecular
      dynamics simulations and (17)O quadrupole coupling tensors.
AB  - Histidine rich protein II derived peptide (HRP II 169-182) was investigated by
      molecular dynamics, MD, simulation and (17)O electric field gradient, EFG, tensor
      calculations. MD simulation was performed in water at 300 K with alpha-helix
      initial structure. It was found that peptide loses its initial alpha-helix
      structure rapidly and is converted to random coil and bent secondary structures.
      To understand how peptide structure affects EFG tensors, initial structure and
      final conformations resulting from MD simulations were used to calculate (17)O
      EFG tensors of backbone carbonyl oxygens. Calculations were performed using B3LYP
      method and 6-31+G basis set. Calculated (17)O EFG tensors were used to evaluate
      quadrupole coupling constants, QCC, and asymmetry parameters, eta(Q). Difference
      between the calculated QCC and eta(Q) values revealed how hydrogen-bonding
      interactions affect EFG tensors at the sites of each oxygen nucleus.

PMID- 18708278
TI  - Molecular surveillance of methicillin-resistant Staphylococcus aureus by multiple
      locus variable number tandem repeat fingerprinting (formerly multiple-locus
      variable number tandem repeat analysis) and spa typing in a hierarchic approach.
AB  - In this study, clonal relatedness of 202 Staphylococcus aureus (mostly
      methicillin-resistant) isolates recovered in 29 Polish hospitals was investigated
      by multiple-locus variable number tandem repeat fingerprinting (MLVF) and spa
      typing. Our analysis yielded 69 MLVF patterns and 34 spa types. Almost all
      isolates (97.4%) identical by MLVF were also indistinguishable by spa typing.
      Therefore, the MLVF method can be a cheap and fast screen before spa typing.
      Moreover, results obtained by MLVF suggest a set of simple criteria for grouping
      of spa types. The proposed algorithm groups isolates into the same cluster when
      spa sequences differ by a single mutation event: i) a single deletion or
      insertion of repeat unit(s) at the X region of the protein A gene or ii) a single
      nucleotide polymorphism within a repeat sequence. The combined use of these 2
      methods, MLVF in local laboratories and spa typing of selected isolates in
      reference centers, can improve the monitoring of hospital-to-hospital strain
      transmission events and public health interventions on a huge scale.

PMID- 18708279
TI  - AuSPEN clinical practice guideline for home parenteral nutrition patients in
      Australia and New Zealand.
AB  - OBJECTIVE: Evidence based guidelines for home parenteral nutrition (HPN) were
      commissioned by the Australasian Society of Parenteral and Enteral Nutrition
      (AuSPEN) and developed by a multidisciplinary group. The guidelines make
      recommendations in four domains: patient selection, patient training, formulation
      and monitoring regimens, and preventing and managing complications. METHODS: The
      Appraisal of Guidelines Research and Evaluation guideline process was used to
      focus questions and identify evidence by systematic literature reviews of meta
      analyses and randomized control trials in the Cochrane Library, Medline, Embase,
      and Cinahl to mid-2007. Where no randomized control trial evidence was found, the
      search was broadened to observational studies and expert opinion from related
      national and international guidelines as assessed by a validated appraisal
      process. RESULTS: Selection of patients must assess individual risk/benefit and
      medical ethics. Patient training should be undertaken within a structured
      framework. Access devices should be selected for lowest risk of complications,
      including occlusion, sepsis, and breakage and be managed by early diagnosis and
      treatment. HPN should be formulated according to individual patient requirements
      by professionals with relevant skills and training. Pumps and ancillary products
      should conform to quality standards. Other intravenous medications may be
      prescribed provided these are reviewed for compatibility and effects on metabolic
      status. CONCLUSION: Overall there is a lack of randomized control trials to
      provide high-quality evidence-based guidance but graded recommendations can be
      made. Multidisciplinary teams in centers with HPN management expertise are
      required for optimal care. This guideline should improve outcomes and quality of
      life for HPN patients in Australia and New Zealand.

PMID- 18708280
TI  - Can persons with schizophrenia appreciate visual art?
AB  - The way schizophrenia patients perceive the world is largely mysterious.
      Understanding and appreciating the visual world begins with the perception of
      basic visual features, which is altered in this mental disorder. Yet, the roles
      basic visual features play in functional activities such as appreciation of art
      are unclear. This study examined the effects of visual feature manipulation on
      beauty perception of art in schizophrenia patients (n=29) and in normal controls
      (n=30). Three pieces of art--The Starry Night (Van Gogh), Mona Lisa (Da Vinci)
      and a natural landscape photograph (anonymous)--were manipulated in terms of
      their coloration (removal of color), spatial frequency content (low or high
      frequency pass) and visual noise level (with added noise). Subjects judged the
      beauty of the original and visual-feature-manipulated artworks by rating each
      piece individually (1 to 7) and by ranking all pieces from most to least
      beautiful. For the three original art pieces, averaged ratings and rankings were
      similar in patients and controls. However, when the visual features of the
      original pieces were manipulated, changes in the beauty ratings were
      significantly smaller in patients. The reduced sensitivity to visual feature
      manipulations suggests that the modulation of basic visual signals, often used
      for vivid and dynamic expressions in art, may be under-appreciated in
      schizophrenia.

PMID- 18708281
TI  - Sniff and Muller manoeuvres to measure diaphragmatic muscle strength.
AB  - We hypothesized that peak values of oesophageal (Poes) and transdiaphragmatic
      pressure (Pdi) swings during a maximal sniff manoeuvre and a maximal static
      inspiratory manoeuvre (Muller manoeuvre) are comparable or give complementary
      information for assessing diaphragmatic and global inspiratory muscle strength.
      We studied 98 patients with suspected diaphragmatic dysfunction. Poes and Pdi
      swings were measured during maximal sniff manoeuvres (sniff), maximal Muller
      manoeuvres (max), and cervical magnetic phrenic nerve stimulation (cervical Tw).
      Eighty eight patients were able to perform both volitional manoeuvres. Among
      them, mean Poes sniff was significantly higher than mean Poes max (48.7+/-28.7 cm
      H(2)O vs. 42.9+/-27.4 cm H(2)O, p<0.05) and mean Pdi sniff was higher than mean
      Pdi max (49.2+/-35.1cm H(2)O vs. 42.9+/-33.3 cm H(2)O, respectively, p=0.05).
      Cervical Pdi Tw correlated better with Pdi sniff (p<0.0001, r=0.62) than with Pdi
      max (p<0.0001, r=0.44). Poes and Pdi swings were greatest during the sniff
      manoeuvre in 42 patients (48%) and during the Muller manoeuvre in 29 patients
      (33%). Among the 17 remaining patients, nine had the greatest Poes swing during a
      maximal sniff manoeuvre and the greatest Pdi swing during a maximal static
      inspiratory manoeuvre; the opposite occurred in the other eight patients. The
      combination of Muller manoeuvre and sniff manoeuvre increased the diagnosis of
      normal diaphragmatic strength from 18 patients (20%) to 21 patients (24%), and
      the additional analysis of cervical Pdi Tw further increased the diagnosis of
      normal diaphragmatic strength to 27 patients (31%). In conclusion, though sniff
      manoeuvre gave significantly higher values than Muller manoeuvre, both volitional
      manoeuvres and cervical Pdi Tw are complementary and should be used in
      combination to evaluate diaphragmatic muscle strength.

PMID- 18708282
TI  - Inspiratory muscle training in adults with chronic obstructive pulmonary disease:
      an update of a systematic review.
AB  - The purpose was to update an original systematic review to determine the effect
      of inspiratory muscle training (IMT) on inspiratory muscle strength and
      endurance, exercise capacity, dyspnea and quality of life for adults with chronic
      obstructive pulmonary disease (COPD). The original MEDLINE and CINAHL search to
      August 2003 was updated to January 2007 and EMBASE was searched from inception to
      January 2007. Randomized controlled trials, published in English, with adults
      with stable COPD, comparing IMT to sham IMT or no intervention, low versus high
      intensity IMT, and different modes of IMT were included. Nineteen of 274 articles
      in the original search met the inclusion criteria. The updated search revealed 17
      additional articles; 6 met the inclusion criteria, all of which compared
      targeted, threshold or normocapneic hyperventilation IMT to sham IMT. An update
      of the sub-group analysis comparing IMT versus sham IMT was performed with 10
      studies from original review and 6 from the update. Sixteen meta-analyses are
      reported. Results demonstrated significant improvements in inspiratory muscle
      strength (PI(max), PI(max) % predicted, peak inspiratory flow rate), inspiratory
      muscle endurance (RMET, inspiratory threshold loading, MVV), exercise capacity
      (Ve(max), Borg Score for Respiratory Effort, 6MWT), Transitional Dyspnea Index
      (focal score, functional impairment, magnitude of task, magnitude of effort), and
      the Chronic Respiratory Disease Questionnaire (quality of life). Results suggest
      that targeted, threshold or normocapneic hyperventilation IMT significantly
      increases inspiratory muscle strength and endurance, improves outcomes of
      exercise capacity and one measure of quality of life, and decreases dyspnea for
      adults with stable COPD.

PMID- 18708283
TI  - Femur EPA and DHA are correlated with femur biomechanical strength in young fat-1
      mice.
AB  - Evidence suggests that n-3 polyunsaturated fatty acids (PUFA) are beneficial for
      maintenance of bone health and possibly bone development. This study used the fat
      1 mouse, a transgenic model that synthesizes n-3 PUFA from n-6 PUFA, to determine
      if outcomes of bone health were correlated with n-3 PUFA in femurs. Control and
      fat-1 mice were fed an AIN-93G diet containing 10% safflower oil from weaning
      through 12 weeks of age. Femur bone mineral content (BMC) and density were
      determined by dual-energy X-ray absorptiometry, and biomechanical strength
      properties, surrogate measures of fracture risk, were measured by a materials
      testing system. Femur fatty acid composition was determined by gas
      chromatography. At 12 weeks of age, femur n-3 PUFA were higher among fat-1 mice
      compared to control mice. The n-6/n-3 PUFA ratio in the femur was negatively
      correlated with BMC (r=-.57, P=.01) and peak load at femur midpoint (r=-.53,
      P=.02) and femur neck (r=-.52, P=.02). Moreover, long-chain n-3 PUFA,
      eicosapentaenoic acid, and docosahexaenoic acid were significantly and positively
      correlated or displayed a trend suggesting positive correlations, with BMC and
      peak load. In conclusion, the results of the present study suggest that n-3 PUFA
      have a favorable effect on mineral accumulation and functional measures of bone
      in fat-1 mice at young adulthood.

PMID- 18708284
TI  - Taurine supplementation modulates glucose homeostasis and islet function.
AB  - Taurine is a conditionally essential amino acid for human that is involved in the
      control of glucose homeostasis; however, the mechanisms by which the amino acid
      affects blood glucose levels are unknown. Using an animal model, we have studied
      these mechanisms. Mice were supplemented with taurine for 30 d. Blood glucose
      homeostasis was assessed by intraperitoneal glucose tolerance tests (IPGTT).
      Islet cell function was determined by insulin secretion, cytosolic Ca2+
      measurements and glucose metabolism from isolated islets. Islet cell gene
      expression and translocation was examined via immunohistochemistry and
      quantitative real-time polymerase chain reaction. Insulin signaling was studied
      by Western blot. Islets from taurine-supplemented mice had: (i) significantly
      higher insulin content, (ii) increased insulin secretion at stimulatory glucose
      concentrations, (iii) significantly displaced the dose-response curve for glucose
      induced insulin release to the left, (iv) increased glucose metabolism at 5.6 and
      11.1-mmol/L concentrations; (v) slowed cytosolic Ca2+ concentration ([Ca2+]i)
      oscillations in response to stimulatory glucose concentrations; (vi) increased
      insulin, sulfonylurea receptor-1, glucokinase, Glut-2, proconvertase and pancreas
      duodenum homeobox-1 (PDX-1) gene expression and (vii) increased PDX-1 expression
      in the nucleus. Moreover, taurine supplementation significantly increased both
      basal and insulin stimulated tyrosine phosphorylation of the insulin receptor in
      skeletal muscle and liver tissues. Finally, taurine supplemented mice showed an
      improved IPGTT. These results indicate that taurine controls glucose homeostasis
      by regulating the expression of genes required for glucose-stimulated insulin
      secretion. In addition, taurine enhances peripheral insulin sensitivity.

PMID- 18708285
TI  - Concomitant supplementation of lycopene and eicosapentaenoic acid inhibits the
      proliferation of human colon cancer cells.
AB  - Several studies indicated that people who live in the Mediterranean region have
      very low rates of chronic diseases such as cardiovascular disease and cancer. It
      is well known that Mediterranean-style diet is rich in vegetables, tomato, fruit,
      fish and olive oil. These important dietary components may contribute to lower
      risk of cancer. Lycopene, a major component in tomato, exhibited potential
      anticarcinogenic activity. Previous studies showed that consumption of fish
      containing eicosapentaenoic acid (EPA) correlated with reduced risk of cancer.
      However, the combined effects of lycopene and EPA on the proliferation of human
      colon cancer have not been studied well yet. Thus, we investigated the anticancer
      properties and therapeutic potential of lycopene and EPA in human colon cancer HT
      29 cells. In this study, we determined the combined effects of lycopene and EPA
      on the proliferation of human colon cancer HT-29 cells. We demonstrated that low
      concentration of lycopene and EPA could synergistically inhibit the proliferation
      of colon cancer cells. The inhibitory mechanism was associated with suppression
      of phosphatidylinositol 3-kinase/Akt signaling pathway. Furthermore, treatment of
      lycopene and EPA also synergistically blocked the activation of downstream mTOR
      molecule. Immunocytochemical staining results revealed that lycopene and EPA
      could also up-regulate the expression of apoptotic proteins such as Bax and Fas
      ligand to suppress cell survival. In conclusion, our novel findings suggest that
      lycopene and EPA synergistically inhibited the growth of human colon cancer HT-29
      cells even at low concentration. The inhibitory effects of lycopene and EPA on
      cell proliferation of human colon cancer HT-29 cells were, in part, associated
      with the down-regulation of the PI-3K/Akt/mTOR signaling pathway.

PMID- 18708286
TI  - Long-term effects of overfeeding during lactation on insulin secretion--the role
      of GLUT-2.
AB  - Overnutrition during critical developmental periods is believed to be a risk
      factor for the emergence of metabolic disorders in adulthood. The present study
      investigated the effects of pups overfeeding during lactation on offspring's
      insulin secretion. To study the consequences of overnutrition early in life in
      rats, litter size reduction has been shown to be an appropriate experimental
      model. To induce early postnatal overnutrition, litter size was reduced to three
      pups per litter at the third day following birth [overfed group (OG)]. In the
      control group (CG), the litter size was adjusted to 10 pups per litter. Metabolic
      parameters and glucose-stimulated insulin secretion were assessed. OG pups
      ingested more milk at 10 and 21 days and had an augmented food intake at 1 year
      compared to the CG. Consistently, body weight, body fat, and fasting plasma
      levels of insulin were higher in 1-year-old OG rats. In addition, OG rats
      exhibited enhanced insulin secretion, accompanied by elevated content of GLUT-2
      in pancreatic islets compared to CG. These findings indicate that early postnatal
      overnutrition during a critical developmental period in life may program
      permanent alterations in glucose-stimulated insulin secretion.

PMID- 18708287
TI  - No effect of short-term arginine supplementation on nitric oxide production,
      metabolism and performance in intermittent exercise in athletes.
AB  - Arginine supplementation has been shown to alleviate endothelial dysfunction and
      improve exercise performance through increasing nitric oxide production in
      patients with cardiopulmonary diseases. In addition, arginine supplementation
      could decrease accumulations of lactate and ammonia, metabolites involved in
      development of muscular fatigue. The aim of this study was to investigate the
      effect of short-term arginine supplementation on performance in intermittent
      anaerobic exercise and the underlying mechanism in well-trained male athletes.
      Ten elite male college judo athletes participated with a randomized crossover,
      placebo-controlled design. The subjects consumed 6 g/day arginine (ARG trial) or
      placebo (CON trial) for 3 days then performed an intermittent anaerobic exercise
      test on a cycle ergometer. Blood samples were collected before supplementation,
      before and during exercise and 0, 3, 6, 10, 30 and 60 min after exercise. ARG
      trial had significantly higher arginine concentrations than CON trial at the same
      time point before, during and after exercise. In both trials, nitrate and nitrite
      concentration was significantly higher during and 6 min after exercise comparing
      to the basal concentration. The increase in nitrate and nitrite concentration
      during exercise in both trials was parallel to the increase in plasma citrulline
      concentrations. There was no significant difference between the 2 trials in
      plasma nitrate and nitrite, lactate and ammonia concentrations and peak and
      average power in the exercise. The results of this study suggested that short
      term arginine supplementation had no effect on nitric oxide production, lactate
      and ammonia metabolism and performance in intermittent anaerobic exercise in well
      trained male athletes.

PMID- 18708288
TI  - Low-grade endometrial stromal sarcoma with inferior vena cava tumor thrombus and
      intracardiac extension: radical resection may improve recurrence free survival.
AB  - BACKGROUND: Endometrial stromal sarcoma (ESS) represents 0.2% of all uterine
      malignancies. Based on the mitotic activity, a distinction is made between low
      and high-grade ESS. Although the overall five-year survival rate for low-grade
      ESS exceeds 80%, about 50% of the patients show tumor recurrence, mostly after a
      long latency period. Tumor invasion of the great vessels is extremely rare. We
      describe a patient with advanced low-grade ESS with tumor invasion of the
      infrarenal aorta and the inferior vena cava. The patient presented with a large
      tumor thrombus extending from the inferior vena cava into the right atrium.
      METHODS: Review of literature and identification of 19 patients, including our
      own case report, with advanced low-grade ESS with invasion of the great vessels
      and formation of an inferior vena cava tumor thrombus. RESULTS: All 19 patients
      presented with an abdominal tumor mass and a tumor thrombus protruding into the
      inferior vena cava. The tumor thrombus extended into the right heart cavities in
      nine patients reaching the right atrium in four, the right ventricle in three and
      the pulmonary artery in two patients. There were 5 patients with an advanced
      primary tumor and 14 patients with an advanced recurrent tumor. Seven patients
      presented with synchronous metastatic disease and six patients with a pelvic
      tumor infiltrating the bladder, the rectosigmoid colon or the infrarenal aorta.
      Mean age at surgery was 45.9+/-12.3 years (median 47, range 25-65 years). Tumor
      thrombectomy was accomplished by cavatomy or by right atriotomy after
      installation of a cardiopulmonary bypass. There was no peri-operative mortality
      and a very low morbidity. Radical tumor resections were achieved in 10 patients.
      The follow-up for these 10 patients was 2+/-1.3 years (median 2, range 0.3-4.5
      years). Nine patients remained recurrence free whereas one patient suffered an
      asymptomatic local recurrence. CONCLUSIONS: Low-grade ESS is a rare angioinvasive
      tumor with a high recurrence rate. Resection of an inferior vena cava tumor
      thrombus, even with extension into the right heart cavities, can be performed
      safely. Extensive radical surgery is therefore justified in the treatment of
      advanced tumor manifestations of a low-grade ESS potentially improving recurrence
      free survival.

PMID- 18708289
TI  - Data Self-Recalibration and Mixture Mass Fingerprint Searching (DASER-MMF) to
      enhance protein identification within complex mixtures.
AB  - A novel algorithm based on Data Self-Recalibration and a subsequent Mixture Mass
      Fingerprint search (DASER-MMF) has been developed to improve the performance of
      protein identification from online 1D and 2D-LC-MS/MS experiments conducted on
      high-resolution mass spectrometers. Recalibration of 40% to 75% of the MS spectra
      in a human serum dataset is demonstrated with average errors of 0.3 +/- 0.3 ppm,
      regardless of the original calibration quality. With simple protein mixtures, the
      MMF search identifies new proteins not found in the MS/MS based search and
      increases the sequence coverage for identified proteins by six times. The high
      mass accuracy allows proteins to be identified with as little as three peptide
      mass hits. When applied to very complex samples, the MMF search shows less
      dramatic performance improvements. However, refinements such as additional
      discriminating factors utilized within the search space provide significant gains
      in protein identification ability and indicate that further enhancements are
      possible in this realm.

PMID- 18708290
TI  - Conformations of gas-phase ions of ubiquitin, cytochrome c, apomyoglobin, and
      beta-lactoglobulin produced from two different solution conformations.
AB  - At low pH in solutions of 50% methanol, proteins form expanded denatured states
      (the "H" state). In 90% methanol, proteins form expanded helical denatured states
      with artificial alpha-helices (the "H(c)" state). Gas-phase ions of ubiquitin,
      cytochrome c, apomyoglobin, and native and disulfide-reduced beta-lactoglobulin
      were formed by electrospray ionization (ESI) of the proteins from the H and H(c)
      states in solution. Both states in solution produce the same charge states in
      ESI. The conformations of the ions were studied with cross section measurements
      and gas-phase H/D exchange experiments. The cross sections show that the ions
      retain considerable folded structure. For a given protein and given charge state,
      ions produced from the H and H(c) states showed the same cross sections (within
      approximately 1%). Ions of cytochrome c, apomyoglobin, and native and reduced
      beta-lactoglobulin of a given charge state showed no differences in H/D exchange
      level when produced from the H or H(c) state. However, ubiquitin ions produced
      from the H(c) state consistently exchange fewer ( approximately 13%) hydrogens
      than ions produced from the H state, suggesting that in this case the gas-phase
      protein ions retain some memory of their solution conformations.

PMID- 18708291
TI  - Time-dependent confounding in the study of the effects of regular physical
      activity in chronic obstructive pulmonary disease: an application of the marginal
      structural model.
AB  - PURPOSE: Results from longitudinal studies about the association between physical
      activity and chronic obstructive pulmonary disease (COPD) may have been biased
      because they did not properly adjust for time-dependent confounders. Marginal
      structural models (MSMs) have been proposed to address this type of confounding.
      We sought to assess the presence of time-dependent confounding in the association
      between physical activity and COPD development and course by comparing risk
      estimates between standard statistical methods and MSMs. METHODS: By using the
      population-based cohort Copenhagen City Heart Study, 6,568 subjects selected from
      the general population in 1976 were followed up until 2004 with three repeated
      examinations. RESULTS: Moderate to high compared with low physical activity was
      associated with a reduced risk of developing COPD both in the standard analysis
      (odds ratio [OR] 0.76, p = 0.007) and in the MSM analysis (OR 0.79, p = 0.025).
      In the subgroup with COPD (n = 2,226), high physical activity was associated with
      a reduced risk of COPD admissions during follow-up (standard, incidence rate
      ratio, 0.74; p = 0.096; MSM, 0.68, p = 0.044), and with a reduced risk of
      mortality (standard, hazard ratio 0.80, p = 0.001; MSM, 0.81, p = 0.008).
      CONCLUSION: These results support the previously reported associations between
      physical activity and reduced risk of COPD development, hospitalizations, and
      mortality, thereby suggesting they were not due to time-dependent confounding.

PMID- 18708292
TI  - A case of congenital red cell pyruvate kinase deficiency associated with
      hereditary stomatocytosis.

PMID- 18708293
TI  - Cognitive functioning in Williams syndrome: a study in Portuguese and Spanish
      patients.
AB  - Williams Syndrome (WS) is a genetic neurodevelopmental disorder caused by a
      submicroscopic deletion on chromosome 7 q11.23. This is a systemic disorder in
      which cardiac problems and mental retardation are the key phenotypic symptoms.
      Although displaying a general cognitive impairment, they are most often described
      as exhibiting a peak and valley profile, with relative sparing of language and
      face processing abilities and severe impairment of visual-spatial cognition. In
      this study, we conducted a detailed cognitive assessment using Wechsler
      Intelligence Scales on a WS and a normal development control group. To explore
      the hypothesis of a dissociative cognitive architecture in WS, performance on
      subtests, factorial indexes and composite measures of Verbal, Performance and
      Full Scale Intelligence Quotient were analysed. Individuals with WS were found to
      score in Full Scale Intelligence Quotient (FSIQ) within mild to moderate mental
      retardation interval, and had significantly lower scores in all measures when
      they were compared with the normal development group. However, a specific
      intragroup cognitive profile was found for Williams Syndrome (confirming Mervis'
      definition of the WS cognitive profile) along with a specific developmental
      pathway (absence of an age-associated cognitive decline).

PMID- 18708294
TI  - Identical twins with Idiopathic Basal Ganglia Calcification ("Fahr's Disease")
      presenting with a remarkably similar pattern of neuroimaging findings.

PMID- 18708295
TI  - MRI with a lymph-node-specific contrast agent as an alternative to CT scan and
      lymph-node dissection in patients with prostate cancer: a prospective multicohort
      study.
AB  - BACKGROUND: In patients with prostate cancer who are deemed to be at intermediate
      or high risk of having nodal metastases, invasive diagnostic pelvic lymph-node
      dissection (PLND) is the gold standard for the detection of nodal disease.
      However, a new lymph-node-specific MR-contrast agent ferumoxtran-10 can detect
      metastases in normal-sized nodes (ie, <8 mm in size) by use of MR
      lymphoangiography (MRL). In this prospective, multicentre cohort study, we aimed
      to compare the diagnostic accuracy of MRL with up-to-date multidetector CT
      (MDCT), and test the hypothesis that a negative MRL finding obviates the need for
      a PLND. METHODS: We included consecutive patients with prostate cancer who had an
      intermediate or high risk (risk of >5% according to routinely used nomograms) of
      having lymph-node metastases. All patients were assessed by MDCT and MRL, and
      underwent PLND or fine-needle aspiration biopsy. Imaging results were correlated
      with histopathology. The primary outcomes were sensitivity, specificity,
      accuracy, NPV, and PPV of MRL and MDCT. This study is registered with
      ClinicalTrials.gov, number NCT00185029. FINDINGS: The study was done in 11
      hospitals in the Netherlands between April 8, 2003, and April 19, 2005. 375
      consecutive patients were included. 61 of 375 (16%) patients had lymph-node
      metastases. Sensitivity was 34% (21 of 61; 95% CI 23-48) for MDCT and 82% (50 of
      61; 70-90) for MRL (McNemar's test p<0.05). Specificity was 97% (303 of 314; 94
      98) for MDCT and 93% (291 of 314; 89-95) for MRL. Positive predictive value (PPV)
      was 66% (21 of 32; 47-81) for MDCT and 69% (50 of 73; 56-79) for MRL. Negative
      predictive value (NPV) was 88% (303 of 343; 84-91) for MDCT and 96% (291 of 302;
      93-98) for MRL (McNemar's test p<0.05). Of the 61 patients with lymph-node
      metastases, 50 were detected by MRL, of which 40 (80%) had metastases in normal
      sized lymph nodes. The high sensitivity and NPV of MRL imply that in patients
      with a negative MRL, the chance of positive lymph nodes is less than 11/302 (4%).
      INTERPRETATION: MRL had significantly higher sensitivity and NPV than MDCT for
      patients with prostate cancer who had intermediate or high risk of having lymph
      node metastases. In such patients, after a negative MRL, the post-test
      probability of having lymph-node metastases is low enough to omit a PLND.

PMID- 18708296
TI  - Chronic granulomatous disease in Israel: clinical, functional and molecular
      studies of 38 patients.
AB  - Chronic granulomatous disease (CGD) is an innate immunodeficiency due to a
      genetic defect in one of the NADPH-oxidase components. In the course of 21 years,
      38 Israeli CGD patients were diagnosed with 17 gene mutations, seven of which
      were new. Clinical, functional, and molecular studies were accomplished. Although
      X-linked recessive (XLR)-CGD is worldwide the most common genotype of the disease
      (~70%), in our study only 11 patients (29%) suffered from XLR-CGD. In Israel, the
      higher incidence of the autosomal recessive (AR) form of CGD (63%) may be related
      to consanguineous marriages. In three patients (8%), all four proteins of the
      NADPH oxidase were present. Severe clinical expression was found both in the XLR
      and AR forms, but in general a milder disease was evident in AR-CGD, particularly
      in patients with p47(phox) deficiency. Despite early and aggressive therapy, a
      mortality rate of 26% was noted. Given that bone-marrow transplantation was
      successful in five of seven patients, it is recommended to perform it as early as
      possible before tissue damage is irreversible.

PMID- 18708298
TI  - Radioimmunoassay for autoantibodies against interferon omega; its use in the
      diagnosis of autoimmune polyendocrine syndrome type I.
AB  - Patients with the autoimmune polyendocrine syndrome I (APS I) have high titers of
      neutralizing IgG autoantibodies against type I interferons (IFNs), in particular
      IFN-omega. Until now, the most specific assay has been the antiviral interferon
      neutralizing assay (AVINA), which has the drawbacks of requiring a cytolytic
      virus, being cumbersome and difficult to standardise. We have developed a fast
      and reliable immunoassay based on radiolabelled IFN-omega for quantifying anti
      IFN-omega antibodies. Sera from 48 APS I patients were analysed together with
      those from 5 control groups. All sera from APS I patients were positive for anti
      IFN-omega, while, except one serum, all sera from the controls were negative.
      This method has the advantage over bioassays that it is readily adapted to high
      throughput. It provides an alternative, sensitive and specific diagnostic test
      for APS I, and an ideal screening tool to precede mutational analyses of the AIRE
      gene in suspected APS I cases.

PMID- 18708297
TI  - Association of common mitochondrial DNA variants with multiple sclerosis and
      systemic lupus erythematosus.
AB  - Mitochondrial dysfunction has been implicated in the pathogenesis of multiple
      sclerosis (MS) and systemic lupus erythematosus (SLE). This study re-investigates
      the roles of previously suggested candidate genes of energy metabolism (Complex I
      genes located in the nucleus and in the mitochondria) in patients with MS
      relative to ethnically matched SLE patients and healthy controls. After stringent
      correction for multiple testing, we reproduce the association of the
      mitochondrial (mt)DNA haplotype K* with MS, but reject the importance of
      previously suggested borderline associations with nuclear genes of Complex I. In
      addition, we detect the association of common variants of the mitochondrial ND2
      and ATP6 genes with both MS and SLE, which raises the possibility of a shared
      mitochondrial genetic background of these two autoimmune diseases.

PMID- 18708299
TI  - Neurophysiology of the cortical pain network: revisiting the role of S1 in
      subjective pain perception via standardized low-resolution brain electromagnetic
      tomography (sLORETA).
AB  - Multiple studies have supported the usefulness of standardized low-resolution
      brain electromagnetic tomography (sLORETA) in localizing generators of scalp
      recorded potentials. The current study implemented sLORETA on pain event-related
      potentials, primarily aiming at validating this technique for pain research by
      identifying well-known pain-related regions. Subsequently, we pointed at
      investigating the still-debated and ambiguous topic of pain intensity coding at
      these regions, focusing on their relative impact on subjective pain perception.
      sLORETA revealed significant activations of the bilateral primary somatosensory
      (SI) and anterior cingulate cortices and of the contralateral operculoinsular and
      dorsolateral prefrontal (DLPFC) cortices (P < .05 for each). Activity of these
      regions, excluding DLPFC, correlated with subjective numerical pain scores (P <
      .05 for each). However, a multivariate regression analysis (R = .80; P = .024)
      distinguished the contralateral SI as the only region whose activation magnitude
      significantly predicted the subjective perception of noxious stimuli (P = .020),
      further substantiated by a reduced regression model (R = .75, P = .008). Based on
      (1) correspondence of the pain-activated regions identified by sLORETA with the
      acknowledged imaging-based pain-network and (2) the contralateral SI proving to
      be the most contributing region in pain intensity coding, we found sLORETA to be
      an appropriate tool for relevant pain research and further substantiated the role
      of SI in pain perception. PERSPECTIVE: Because the literature of pain intensity
      coding offers inconsistent findings, the current article used a novel tool for
      revisiting this controversial issue. Results suggest that it is the activation
      magnitude of SI, which solely establishes the significant correlation with
      subjective pain ratings, in accordance with the classical clinical thinking,
      relating SI lesions to diminished perception of pain. Although this study cannot
      support a causal relation between SI activation magnitude and pain perception,
      such relation might be insinuated.

PMID- 18708300
TI  - Analgesic efficacy and safety of oxycodone in combination with naloxone as
      prolonged release tablets in patients with moderate to severe chronic pain.
AB  - This randomized, double-blind, placebo- and active-controlled, parallel-group
      study was designed to demonstrate the superiority of oxycodone in combination
      with naloxone in a prolonged release (PR) formulation over placebo with respect
      to analgesic efficacy. The active control group was included for sensitivity and
      safety analyses, and furthermore to compare the analgesic efficacy and bowel
      function of oxycodone PR/naloxone PR with oxycodone PR alone. The analgesic
      efficacy was measured as the time from the initial dose of study medication to
      multiple pain events (ie, inadequate analgesia) in patients with moderate to
      severe chronic low back pain. The full analysis population consisted of 463
      patients. The times to recurrent pain events were significantly longer in the
      oxycodone PR/naloxone PR group compared with placebo (P < .0001-.0003); oxycodone
      PR/naloxone PR reduced the risk of pain events by 42% (P < .0001; full analysis
      population). The appearance of pain events was comparable for oxycodone
      PR/naloxone PR versus oxycodone PR, confirming that the addition of naloxone PR
      to oxycodone PR in a combination tablet did not negatively affect analgesic
      efficacy of the opioid. Furthermore, oxycodone PR/naloxone PR offers benefits in
      terms of an improvement in bowel function. In a therapeutic area of great unmet
      need, therefore, the combination tablet of oxycodone PR/naloxone PR offers
      patients effective analgesia while improving opioid-induced bowel dysfunction.
      Taken together with the observation that the safety profile of oxycodone
      PR/naloxone PR is consistent with that expected from other opioid analgesics
      except opioid-induced constipation, these findings indicate that the addition of
      naloxone to oxycodone in a PR combination tablet offers improved tolerability.
      Oxycodone PR/naloxone PR is therefore a promising new treatment approach for the
      management of chronic pain. PERSPECTIVE: This study evaluated the analgesic
      efficacy and safety of the combination of oxycodone PR/naloxone PR in chronic
      nonmalignant pain. Opioids are often reduced in dosage or even discontinued as a
      result of impaired bowel function, leading to insufficient pain treatment. Not
      only does oxycodone PR/naloxone PR demonstrate analgesic efficacy comparable with
      oxycodone PR, but it also improves opioid-induced bowel dysfunction, and may
      therefore improve the acceptability of long-term opioid treatment for chronic
      pain.

PMID- 18708301
TI  - The multidimensionality of fear of pain: construct independence for the fear of
      Pain Questionnaire-Short Form and the Pain Anxiety Symptoms Scale-20.
AB  - Current fear-anxiety-avoidance models of chronic pain emphasize pain-related fear
      and anxiety as potential precursors for disabling chronic pain; however, anxiety
      and fear are often used interchangeably when discussing pain. Fear is a present
      oriented emotive state associated with an imminent threat (eg, a patient about to
      receive an injection), whereas anxiety is a more general, future-oriented emotive
      state, that occurs in anticipation of threats without requiring an objective
      stimulus (eg, the possibility of receiving an injection). Theoretical and
      empirical evidence suggests pain-related fear and anxiety represent distinct
      cognitive constructs. Moreover, pain-related anxiety has been posited as a
      manifestation of anxiety sensitivity, which has implications for several
      theoretical models as well as treatment. The Fear of Pain Questionnaire and the
      Pain Anxiety Symptoms Scale-20 are popular measures, often used comparably, that
      were designed to measure pain-related fear and anxiety, respectively. These
      measures, along with the Anxiety Sensitivity Index, were administered to an
      undergraduate sample (N = 268; 66% women). Results of confirmatory factor
      analyses suggest each measure represents a related, but distinct, construct.
      Furthermore, correlations with anxiety sensitivity suggest that pain-related
      anxiety may be better conceptualized as a fundamental fear. Implications and
      directions for future research are discussed. PERSPECTIVE: Fear-anxiety-avoidance
      models of chronic pain posit pain-related fear and anxiety as diatheses for
      disabling chronic pain. This research suggests theoretical and clinical
      distinctions between pain-related fear and anxiety. Moreover, pain-related
      anxiety appears more complex than a manifestation of anxiety sensitivity; pain
      related anxiety may be better conceptualized as a fundamental fear.

PMID- 18708302
TI  - Partial infraorbital nerve ligation as a model of trigeminal nerve injury in the
      mouse: behavioral, neural, and glial reactions.
AB  - Trigeminal nerve damage often leads to chronic pain syndromes including
      trigeminal neuralgia, a severely debilitating chronic orofacial pain syndrome.
      Options for treatment of neuropathic pain are limited in effectiveness and new
      approaches based on a better understanding of the underlying pathologies are
      required. Partial ligation has been shown to effectively mimic many of the
      qualities of human neuropathic pain syndromes. We have devised a mouse model of
      trigeminal neuralgia using a partial infraorbital nerve ligation (pIONL) that
      induces persistent pain behaviors and morphological changes in the brainstem. We
      found that the pIONL effectively induced mechanical allodynia lasting for more
      than 3 weeks. Cell proliferation (bromodeoxyuridine), activation of astrocytes
      and microglia in the ipsilateral caudal medulla, and persistent satellite cell
      reaction in the ipsilateral ganglion were observed. Neurochemical markers
      calcitonin gene-related peptide, substance P were decreased in medullary dorsal
      horn ipsilateral to the injury side, whereas substance P receptor NK1 expression
      was increased after 8 days. Nerve injury marker ATF3 was markedly increased in
      ipsilateral trigeminal ganglion neurons at 8 days after pIONL. The data indicate
      that partial trigeminal injury in mice produces many persistent anatomical
      changes in neuropathic pain, as well as mechanical allodynia. PERSPECTIVE: This
      study describes the development of a new mouse model of trigeminal neuropathic
      pain. Our goal is to devise better treatments of trigeminal pain, and this will
      be facilitated by characterization of the underlying cellular and molecular
      neuropathological mechanisms in genetically designed mice.

PMID- 18708304
TI  - Dieulafoy lesion after Roux-en-Y gastric bypass.

PMID- 18708305
TI  - The 2008 Edward E. Mason Founders lecture: interdisciplinary teams in the
      development of "best practice" obesity surgery.

PMID- 18708306
TI  - Effect of preoperative weight loss on laparoscopic gastric bypass outcomes.
AB  - BACKGROUND: Requiring patients to lose weight before weight reduction surgery is
      controversial. The goal of this study was to determine whether preoperative
      weight loss affects laparoscopic Roux-en-Y gastric bypass surgery outcomes.
      METHODS: The medical records of all laparoscopic Roux-en-Y gastric bypass
      patients from September 1, 2001 to March 31, 2005 were retrospectively reviewed
      in our prospective database. Depending on their habitus, patients were
      selectively required to lose >4.54 kg (10 lb) preoperatively (WL group). Their
      outcomes were compared with those of the patients not required to lose weight
      preoperatively (no-WL group). Statistical analysis was performed with the chi
      square test and Student's t test for demographic data. Student's t test was used
      to assess the outcome data. P <.05 was considered significant. RESULTS: Of the
      353 patients, 74 (21%) were in the WL group. The operative times in the WL group
      averaged 10 minutes longer than in the no-WL group (P = .022). The mean length of
      stay was not significantly different between the 2 groups. Of the 353 patients,
      262 (74%) completed 1 year of follow-up. The mean net postoperative weight loss
      was not significantly different between the 2 groups. The no-WL patients had a
      greater percentage of excess postoperative weight loss than the WL group (74%
      versus 66%; P = .01). Net complications occurred less frequently in the WL group
      (P = .035). CONCLUSION: Preoperative weight loss did not decrease the operative
      times or the length of stay. Preoperative weight loss increased neither the mean
      net postoperative weight loss nor the percentage of excess postoperative weight
      loss at 1-year follow-up. However, the WL group had fewer net complications.

PMID- 18708307
TI  - Mesh expansion and fixation at the recto-rectus plane through multiple stabs by
      using two tip hole needles in midline hernias repair. A prospective study.
AB  - OBJECTIVE: Midline hernias are a common surgical problem and numerous procedures
      of repair have been described, but there is no consensus about which type of
      these procedures are the best. Stabbing technique for midline hernias repair is a
      procedure collecting the advantages of laparoscopic and traditional open
      techniques, and avoids the complications of both of them. METHODS: In the present
      study, 60 patients with midline hernias were subjected to retro-rectus prosthetic
      mesh repair using stabbing method and by helping special fork which has two tip
      hole needles, from February 2004 through March 2006 at General Surgery
      Department, Faculty of Medicine, Zagazig University, Egypt. Small laparotomy
      incision was done over hernial sac, the contents were then released and reduced
      into the peritoneal cavity without much subcutaneous dissection. The suitable
      sheet of polypropylene mesh to cover the hernial defect and any weak area of the
      anterior abdominal sheath all around by about 5 cm was prepared and fixed at
      retro-rectus plane through multiple small stabs incisions in skin of the
      abdominal wall by using a special fork. The mean period of follow up was 36
      months. RESULTS: The postoperative convalescence was uneventful, and no
      recurrence has been recorded. CONCLUSION: The stabbing technique for mesh
      fixation at retro-rectus plane offers a viable option for midline hernias repair
      without special complications.

PMID- 18708308
TI  - Can surgeon familiarization with current evidence lead to a change in practice? A
      prospective study.
AB  - BACKGROUND: Despite evidence against its utility, many surgeons continue to
      employ prophylactic nasogastric decompression in elective colonic resection. This
      study aimed to establish whether an easy and practical intervention, mailing out
      a summary of current evidence to surgeons, can change surgeons practice to bring
      it more in line with current evidence. METHODS: The use of prophylactic
      nasogastric (NG) decompression in elective colonic resections was documented for
      the 2 consecutive months of October and November, 2004 at the Royal Alexandra
      Hospital (RAH). A one page summary of recent evidence concerning this practice
      was then mailed to all general surgeons at that institution. A similar second
      review was carried out for the months of January and February, 2005. The two
      periods were compared with regards to prophylactic NG use. RESULTS: Twenty two
      patients underwent elective colonic resections during the months of October and
      November, 2004. Twenty one patients underwent such procedures in January and
      February, 2005. Seven out of the 22 cases in the first group (the pre
      intervention block) received prophylactic NG decompression. Five out of the 21
      cases in the second group (the post-intervention block) received prophylactic NG
      decompression. The difference in prophylactic NG use between the two groups was
      not statistically significant. CONCLUSIONS: This study has shown that mailing out
      a summary of current evidence to surgeons concerning a certain issue is not
      sufficient to lead to a change in practice.

PMID- 18708309
TI  - Preoperative planning for DIEP breast reconstruction: early experience of the use
      of computerised tomography angiography with VoNavix 3D software for perforator
      navigation.
AB  - The deep inferior epigastric perforator (DIEP) flap is normally the first choice
      in breast reconstruction; however, due to the considerable vascular anatomical
      variation and the learning curve for the procedure, muscle-sparing transverse
      rectus abdominis musculocutaneous (TRAM) flaps are still frequently performed to
      reduce the rate of complications. Accurate preoperative investigation of the
      perforators would allow better operative preparation and possibly shorten the
      learning curve. In an effort to increase accuracy of preoperative planning and to
      aid preoperative decision-making in free abdominal flap breast reconstruction, we
      have acquired the use of VoNavix, software that creates three dimensional images
      from computerised tomography angiography (CTA) data. The use of the VoNavix
      software for analysis of CTA provides superior imaging that can be viewed in
      theatre. It, together with CTA, enables decisions to be made preoperatively,
      including: which side to raise the flap; whether to aim for a medial or lateral
      row perforator; whether to take a segment of muscle and whether to expect an easy
      or difficult dissection. We have now performed over 60 free abdominal flap breast
      reconstructions aided with CTA, and 10 of these cases also used VoNavix
      technology. This paper presents our initial experience with the use of this
      software, illustrated with three patient examples. The advantages and
      disadvantages are discussed.

PMID- 18708310
TI  - Autologous fat transplantation for the treatment of Parry-Romberg syndrome.
AB  - Progressive facial hemiatrophy or Parry-Romberg syndrome is characterised by
      slowly progressive atrophy of one side of the face, primarily involving the
      subcutaneous tissue and fat. The restoration of contour and symmetry is the main
      challenge in patients affected by this syndrome. We describe the case of a
      patient with stabilised mild hemifacial atrophy, successfully treated by
      autologous fat transplantation. Although two- or three-stage fat grafting may be
      needed in order to accomplish the desired result, in this specific case it was
      achieved in a single procedure. An accurate soft tissue substitution with
      creation of multiple subcutaneous and intramuscular tunnels for lipografting
      ensured adequate blood supply of the transplanted fat. The aesthetic improvement
      and the patient satisfaction show that autologous fat transplantation could be a
      safe technique for the correction of the mild Parry-Romberg syndrome.

PMID- 18708311
TI  - Use of carbonated calcium phosphate bone cement and resorbable plates for the
      treatment of frontal sinus fractures: two case reports.

PMID- 18708312
TI  - [Rasburicase therapy may cause hydrogen peroxide shock].
AB  - Hyperuricemia contributes to the pathomechanism of diseases such as renal
      failure, gout, tumor lysis syndrome and metabolic syndrome. Tumor lysis syndrome
      is a complication of malignancies caused by massive tumor cell lysis due to
      either spontaneous tumor cell lysis or to different therapies and it may cause
      hyperuricemia. Recently, for treatment of hyperuricemia the recombinant urate
      oxidase (rasburicase) therapy has been used. This enzyme converts uric acid with
      high affinity into soluble allantoin which is eliminated by the kidneys. In this
      reaction high concentration of hydrogen peroxide is generated. This hydrogen
      peroxide could cause hemolysis and especially methemoglobin formation, in case of
      glucose-6-phosphate-dehydrogenase and catalase deficiencies. Therefore it is
      recommended that these enzymes are determined before therapy. For monitoring of
      rasburicase therapy the determination of serum uric acid concentration is used.
      More than 95 per cent of Hungarian clinical laboratories are using the uricate
      oxidase/peroxidase reactions and hydrogen peroxide measurements in the uric acid
      assays. These assays may be interfered by ascorbic acid and hydrogen peroxide
      which is generated by rasburicase either in vivo or in vitro.

PMID- 18708313
TI  - [Maternally inherited diabetes mellitus, deafness, chronic progressive external
      ophthalmoplegia and myopathy as the result of A3243G mutation of mtDNA].
AB  - Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)
      syndrome are caused mainly by the A3243G mutation of the mitochondrial genome.
      The A3243G substitution of mitochondrial DNA (mtDNA) is also responsible for
      various, other clinical phenotypes and syndromes. Here we report the case of a 33
      year-old woman, with childhood onset ophthalmoplegia externa, progressive,
      generalised exercise intolerability, muscle weakness, hypacusis and diabetes
      mellitus as the symptoms of mitochondrial disease. Genetic analysis of the
      mitochondrial DNA revealed a heteroplasmic A to G substitution at position 3243
      in the tRNS Leu(UUR) gene. In our case the classical MELAS phenotype has not yet
      appeared, however, some examples show in the literature that maternally inherited
      diabetes mellitus, progressive hypacusis, progressive ophthalmoplegia externa,
      exercise intolerance, and myopathy are often linked to as isolated symptoms of
      A3243G mutation. The phenotype in the family is consistent, the proband's
      daughter has ptosis, exercise intolerance, and myopathy, too. A brief summary of
      the different clinical phenotypes associated with A3243G mutation, and of the
      different mtDNA mutations which can cause chronic progressive ophthalmoplegia
      externa (CPEO) will also be reviewed in this case report.

PMID- 18708314
TI  - [The motivational value foundations in the choice of career among professional
      nursing students and students studying at teacher's college].
AB  - For the profession of teachers and nurses we need well-trained, highly qualified
      employees with a sense of vocation. AIM: A comparative analysis of motivation in
      the choice of career among professional nursing students and teacher-students.
      METHODS: This analysis was done in Hungary among professional nursing students
      and students participating in teacher training. In this sample 783 students were
      analysed. RESULTS: In the choice of career of nurses and teachers the primary
      motivation is of altruistic nature and also the human characteristics of the
      chosen career. According to genders in the case of female interviewed people we
      got a higher value than in the case of males in connection with "Helping people".
      It is more typical in the case of professional nursing students to choose the
      career as early as in their childhood. Choosing the career at a later age is
      typical for those who are teacher-students. CONCLUSION: As a consequence of our
      rapid economic changes or because of career dissatisfaction, we have to face the
      fact that the qualifications obtained at a young age will not last for a life
      time, and the majority of people are forced to change their jobs several times
      during their lives. In harmonizing the demands of the labour market and
      education, those people who take part in professional education and training have
      a professional advantage.

PMID- 18708315
TI  - [Tuberculosis].

PMID- 18708316
TI  - [Greeting Emil Schultheisz at his 85th birthday].

PMID- 18708317
TI  - [Excerpts from the history of Hungarian rural health care from the issue of
      Generalae Normativum in Re Sanitatis till 1945].

PMID- 18708318
TI  - [The last meeting of the German Democratic Republic's Society for History of
      Medicine. Magdeburg, 22-25 September, 1990 (a late report)].

PMID- 18708320
TI  - [Diagnostics of autoimmune pancreatitis].

PMID- 18708321
TI  - [Let us not allow Karoly Schaffer, the discoverer of the pathogenesis of Tay
      Sachs-disease, to suffer the fate of Semmelweis].

PMID- 18708322
TI  - Anomalous diffusion of heterogeneous populations characterized by normal
      diffusion at the individual level.
AB  - The characterization of the dispersal of populations of non-identical individuals
      is relevant to most ecological and epidemiological processes. In practice, the
      movement is quantified by observing relatively few individuals, and averaging to
      estimate the rate of dispersal of the population as a whole. Here, we show that
      this can lead to serious errors in the predicted movement of the population if
      the individuals disperse at different rates. We develop a stochastic model for
      the diffusion of heterogeneous populations, inspired by the movement of the
      parasitic nematode Phasmarhabditis hermaphrodita. Direct observations of this
      nematode in homogeneous and heterogeneous environments reveal a large variation
      in individual behaviour within the population as reflected initially in the speed
      of the movement. Further statistical analysis shows that the movement is
      characterized by temporal correlations and in a heterogeneously structured
      environment the correlations that occur are of shorter range compared with those
      in a homogeneous environment. Therefore, by using the first-order correlated
      random walk techniques, we derive an effective diffusion coefficient for each
      individual, and show that there is a significant variation in this parameter
      among the population that follows a gamma distribution. Based on these findings,
      we build a new dispersal model in which we maintain the classical assumption that
      individual movement can be described by normal diffusion, but due to the
      variability in individual dispersal rates, the diffusion coefficient is not
      constant at the population level and follows a continuous distribution. The
      conclusions and methodology presented are relevant to any heterogeneous
      population of individuals with widely different diffusion rates.

PMID- 18708323
TI  - Sharing the burden: antigen transport and firebreaks in immune responses.
AB  - Communication between cells is crucial for immune responses. An important means
      of communication during viral infections is the presentation of viral antigen on
      the surface of an infected cell. Recently, it has been shown that antigen can be
      shared between infected and uninfected cells through gap junctions, connexin
      based channels, that allow the transport of small molecules. The uninfected cell
      receiving antigen can present it on its surface. Cells presenting viral antigen
      are detected and killed by cytotoxic T lymphocytes. The killing of uninfected
      cells can lead to increased immunopathology. However, the immune response might
      also profit from killing those uninfected bystander cells. One benefit might be
      the removal of future 'virus factories'. Another benefit might be through the
      creation of 'firebreaks', areas void of target cells, which increase the
      diffusion time of free virions, making their clearance more likely. Here, we use
      theoretical models and simulations to explore how the mechanism of gap junction
      mediated antigen transport (GMAT) affects the dynamics of the virus and immune
      response. We show that under the assumption of a well-mixed system, GMAT leads to
      increased immunopathology, which always outweighs the benefit of reduced virus
      production due to the removal of future virus factories. By contrast, a spatially
      explicit model leads to quite different results. Here we find that the firebreak
      mechanism reduces both viral load and immunopathology. Our study thus shows the
      potential benefits of GMAT and illustrates how spatial effects may be crucial for
      the quantitative understanding of infection dynamics and immune responses.

PMID- 18708325
TI  - In situ detection of tree root distribution and biomass by multi-electrode
      resistivity imaging.
AB  - Traditional methods for studying tree roots are destructive and labor intensive,
      but available nondestructive techniques are applicable only to small scale
      studies or are strongly limited by soil conditions and root size. Soil electrical
      resistivity measured by geoelectrical methods has the potential to detect
      belowground plant structures, but quantitative relationships of these
      measurements with root traits have not been assessed. We tested the ability of
      two-dimensional (2-D) DC resistivity tomography to detect the spatial variability
      of roots and to quantify their biomass in a tree stand. A high-resolution
      resistivity tomogram was generated along a 11.75 m transect under an Alnus
      glutinosa (L.) Gaertn. stand based on an alpha-Wenner configuration with 48
      electrodes spaced 0.25 m apart. Data were processed by a 2-D finite-element
      inversion algorithm, and corrected for soil temperature. Data acquisition,
      inversion and imaging were completed in the field within 60 min. Root dry mass
      per unit soil volume (root mass density, RMD) was measured destructively on soil
      samples collected to a depth of 1.05 m. Soil sand, silt, clay and organic matter
      contents, electrical conductivity, water content and pH were measured on a subset
      of samples. The spatial pattern of soil resistivity closely matched the spatial
      distribution of RMD. Multiple linear regression showed that only RMD and soil
      water content were related to soil resistivity along the transect. Regression
      analysis of RMD against soil resistivity revealed a highly significant logistic
      relationship (n = 97), which was confirmed on a separate dataset (n = 67),
      showing that soil resistivity was quantitatively related to belowground tree root
      biomass. This relationship provides a basis for developing quick nondestructive
      methods for detecting root distribution and quantifying root biomass, as well as
      for optimizing sampling strategies for studying root-driven phenomena.

PMID- 18708324
TI  - Development of free-energy-based models for chaperonin containing TCP-1 mediated
      folding of actin.
AB  - A free-energy-based approach is used to describe the mechanism through which
      chaperonin-containing TCP-1 (CCT) folds the filament-forming cytoskeletal protein
      actin, which is one of its primary substrates. The experimental observations on
      the actin folding and unfolding pathways are collated and then re-examined from
      this perspective, allowing us to determine the position of the CCT intervention
      on the actin free-energy folding landscape. The essential role for CCT in actin
      folding is to provide a free-energy contribution from its ATP cycle, which drives
      actin to fold from a stable, trapped intermediate I3, to a less stable but now
      productive folding intermediate I2. We develop two hypothetical mechanisms for
      actin folding founded upon concepts established for the bacterial type I
      chaperonin GroEL and extend them to the much more complex CCT system of
      eukaryotes. A new model is presented in which CCT facilitates free-energy
      transfer through direct coupling of the nucleotide hydrolysis cycle to the phases
      of actin substrate maturation.

PMID- 18708327
TI  - Isolation of flowering genes and seasonal changes in their transcript levels
      related to flower induction and initiation in apple (Malus domestica).
AB  - Flower development in apple (Malus domestica Borkh.) extends over two consecutive
      seasons. During the first season, most shoot apical meristems change to
      reproductive growth and initiate flowers. After winter dormancy, flower
      development continues during the second season and ends with anthesis in the
      spring. To determine the beginning of the transition to reproductive growth at
      the molecular level and to identify genes involved in this critical phase of
      flower development, we examined transcript levels of the putative flowering genes
      MdCOL1, MdCOL2, MdFT, MdSOC1, MdMADS2, MdMADS5, MdTFL1-1 and MdTFL1-2 in
      vegetative terminal buds of the apple cultivar Pinova during the first season by
      quantitative real-time PCR. Transcript levels of these genes peaked at the end of
      April during blooming of coexisting floral buds. Subsequently, there was a large
      increase in transcription, which started on May 22 for AFL2 and MdMADS2, followed
      by MdFT and AFL1 one week later. We propose that the increased transcription at
      the end of May marks the beginning of flower induction. Transcript levels of
      MdSOC1, MdTFL1-1 and MdTFL1-2 increased at the end of June, suggesting that these
      genes are involved in flower initiation, which follows flower induction. In
      contrast, MdMADS5 transcription was too weak to be quantified, and the transcript
      levels of MdCOL1 and MdCOL2 showed no detectable trends during the study.

PMID- 18708326
TI  - Identification of early-flower-related ESTs in an early-flowering mutant of
      trifoliate orange (Poncirus trifoliata) by suppression subtractive hybridization
      and macroarray analysis.
AB  - To increase our understanding of the genes involved in flower development in
      citrus, we identified genes differentially expressed between juveniles and adults
      of an early-flowering mutant of trifoliate orange (precocious trifoliate orange,
      Poncirus trifoliata L. Raf.) by suppressive subtractive hybridization (SSH) and
      macroarray hybridization analyses. Based on dot blot analysis, we confirmed that
      the juvenile subtracted cDNA library comprised genes upregulated during floral
      induction, inflorescence development and flowering. A total of 190 nonredundant
      expressed sequence tags were identified that were related flower development. The
      temporal and spatial expression patterns of four SSH-enriched genes were studied
      in adult precocious trifoliate orange by real-time PCR. Among these
      differentially expressed genes, the expression pattern of C5-B16 was closely
      correlated with inflorescence development and flowering. The full-length cDNA of
      C5-B16 was isolated by 5' and 3' rapid amplification of cDNA ends. Sequence
      analysis indicated that C5-B16 is a novel gene in citrus.

PMID- 18708328
TI  - Stem girdling manipulates leaf sugar concentrations and anthocyanin expression in
      sugar maple trees during autumn.
AB  - To better understand the effects of sugar accumulation on red color development
      of foliage during autumn, we compared carbohydrate concentration, anthocyanin
      expression and xylem pressure potential of foliage on girdled versus non-girled
      (control) branches of 12 mature, open-grown sugar maple (Acer saccharum Marsh.)
      trees. Half of the study trees were known to exhibit mostly yellow foliar
      coloration and half historically displayed red coloration. Leaves from both
      girdled and control branches were harvested at peak color expression (i.e.,
      little or no chlorophyll present). Disruption of phloem export by girdling
      increased foliar sucrose, glucose and fructose concentrations regardless of
      historical tree color patterns. Branch girdling also increased foliar anthocyanin
      expression from 50.4 to 66.7% in historically red trees and from 11.7 to 54.2% in
      historically yellow trees, the latter representing about a fivefold increase
      compared with control branches. Correlation analyses indicated a strong and
      consistent relationship between foliar red coloration and sugar concentrations,
      particularly glucose and fructose, in both girdled and control branches. Measures
      of xylem pressure potentials confirmed that girdling was a phloem-specific
      treatment and had no effect on water transport to distal leaves. Results indicate
      that stem girdling increased foliar sugar concentrations and enhanced anthocyanin
      expression during autumn in sugar maple foliage. Native environmental stresses
      (e.g., low autumn temperatures) that reduce phloem transport may promote similar
      physiological outcomes.

PMID- 18708329
TI  - Seasonal acclimation of photosystem II in Pinus sylvestris. I. Estimating the
      rate constants of sustained thermal energy dissipation and photochemistry.
AB  - Acclimation of the partitioning of absorbed light energy in Photosystem II (PSII)
      between photochemical and non-photochemical processes includes short-term
      adjustments that are rapidly reversed in the dark and seasonal acclimation
      processes that are unaffected by dark acclimation. Thus, by using dark-acclimated
      leaves to study the seasonal acclimation of PSII, the confounding effect of short
      term adjustments is eliminated. The maximum quantum yield of photochemistry,
      estimated by chlorophyll fluorescence analysis as F(v)/F(m), where F(v) = (F(m) -
      F(o)), and F(m) and F(o) are maximum and minimum chlorophyll fluorescence,
      respectively, has been widely used to follow the seasonal acclimation of PSII,
      because it is measured in dark-acclimated leaves. Seasonal changes in F(v)/F(m)
      can be caused by adjustments in either the photochemical capacity in PSII, or the
      capacity of thermal dissipation in PSII, or both. However, there is a lack of
      chlorophyll fluorescence parameters that can distinguish between these processes.
      In this study, we introduce two new parameters: the rate constants of sustained
      thermal energy dissipation (k(NPQ)) and of photochemistry (k(P)). We estimated
      k(NPQ) and k(P) from dark-acclimated F(o) and F(m) measured during spring
      recovery of photosynthesis in Scots pine (Pinus sylvestris L.) trees. We suggest
      that k(NPQ) and k(P) be used to study the mechanisms underlying the observed
      seasonal acclimation in PSII, because these parameters provide quantitative data
      that complement and extend F(v)/F(m) measurements.

PMID- 18708330
TI  - Seasonal acclimation of photosystem II in Pinus sylvestris. II. Using the rate
      constants of sustained thermal energy dissipation and photochemistry to study the
      effect of the light environment.
AB  - Photosynthesis in evergreen conifers is characterized by down-regulation in
      autumn and rapid up-regulation in spring. This seasonal pattern is largely driven
      by temperature, but the light environment also plays a role. In overwintering
      Scots pine (Pinus sylvestris L.) trees, PSII is less down-regulated and recovers
      faster from winter stress in shaded needles than in needles exposed to full
      sunlight. Because the effect of light on the seasonal acclimation of PSII has not
      been quantitatively studied under field conditions, we used the rate constants
      for sustained thermal energy dissipation and photochemistry to investigate the
      dynamics and kinetics of the seasonal acclimation of PSII in needles exposed to
      different light environments. We monitored chlorophyll fluorescence and needle
      pigment concentration during the winter and spring in Scots pine seedlings
      growing in the field in different shading treatments, and within the crowns of
      mature trees. The results indicated that differences in acclimation of PSII in
      overwintering Scots pine among needles exposed to different light environments
      can be chiefly attributed to sustained thermal dissipation. We also present field
      evidence that zeaxanthin-facilitated thermal dissipation and aggregation of
      thylakoid membrane proteins are key mechanisms in the regulation of sustained
      thermal dissipation in Scots pine trees in the field.

PMID- 18708331
TI  - Bole girdling affects metabolic properties and root, trunk and branch hydraulics
      of young ponderosa pine trees.
AB  - Effects of trunk girdling on seasonal patterns of xylem water status, water
      transport and woody tissue metabolic properties were investigated in ponderosa
      pine (Pinus ponderosa Dougl. ex P. Laws.) trees. At the onset of summer, there
      was a sharp decrease in stomatal conductance (g(s)) in girdled trees followed by
      a full recovery after the first major rainfall in September. Eliminating the root
      as a carbohydrate sink by girdling induced a rapid reversible reduction in g(s).
      Respiratory potential (a laboratory measure of tissue-level respiration)
      increased above the girdle (branches and upper trunk) and decreased below the
      girdle (lower trunk and roots) relative to control trees during the growing
      season, but the effect was reversed after the first major rainfall. The increase
      in branch respiratory potential induced by girdling suggests that the decrease in
      g(s) was caused by the accumulation of carbohydrates above the girdle, which is
      consistent with an observed increase in leaf mass per area in the girdled trees.
      Trunk girdling did not affect native xylem embolism or xylem conductivity. Both
      treated and control trunks experienced loss of xylem conductivity ranging from
      10% in spring to 30% in summer. Girdling reduced xylem growth and sapwood to leaf
      area ratio, which in turn reduced branch leaf specific conductivity (LSC). The
      girdling-induced reductions in g(s) and transpiration were associated with a
      decrease in leaf hydraulic conductance. Two years after girdling, when root-to
      shoot phloem continuity had been restored, girdled trees had a reduced density of
      new wood, which increased xylem conductivity and whole-tree LSC, but also
      vulnerability to embolism.

PMID- 18708332
TI  - Xylem embolism alleviated by ion-mediated increase in hydraulic conductivity of
      functional xylem: insights from field measurements.
AB  - Recent studies have shown that, in some species, xylem hydraulic conductivity
      (K(h)) increases with increasing cation concentration of xylem sap. Evidence
      indicates that K(h) increases as a result of the de-swelling of pit membrane
      pectins caused by cation neutralization of polygalacturonanes. We tested whether
      this ionic effect partly compensates for the embolism-induced loss of stem
      hydraulic conductivity (PLC) by increasing K(h) of functioning conduits. We
      report changes in PLC, leaf water status and potassium concentration ([K(+)]) of
      xylem sap measured in April and July in two evergreens (Ceratonia siliqua L. and
      Phytolacca dioica L.) and one deciduous tree (Platanus orientalis L.) growing in
      the field in Sicily. In summer, Ceratonia siliqua and Phytolacca dioica showed
      similar native embolism (PLC = 30-40%) and [K(+)] of xylem sap (14 to 17 mM), and
      K(h) of stems perfused with 10 to 25 mM KCl increased by 15 to 18% compared with
      K(h) of stems perfused with a low concentration of a multi-ionic solution. In
      contrast, native [K(+)] of sap of Platanus orientalis was 50% of that in the two
      evergreens in summer, with a parallel lack of detectable changes in PLC that was
      below 10% in both spring and summer. The ionic effect was PLC-dependent: the
      enhancement of K(h) induced by 10 to 25 mM KCl changed from 15% for fully
      hydrated stems to 50-75% for stems with PLC = 50%. In Ceratonia siliqua, PLC was
      less than 10% in spring and about 40% in summer; concurrently, xylem sap [K(+)]
      increased from 3 to about 15 mM. This [K(+)] at the recorded PLC would cause an
      increase in residual K(h) of about 30%. Hence, the actual reduction in water
      transport capacity of Ceratonia siliqua stems in summer is about 20%. Similar
      calculations for Phytolacca dioica suggest that the actual loss of hydraulic
      conductivity in stems of this species in summer would be only about 10%, and not
      30% as suggested by hydraulic measurements performed in the laboratory. We
      conclude that an increase in [K(+)] of xylem sap might be involved in the up
      regulation of residual K(h), thus substantially alleviating the embolism-induced
      reduction in leaf water supply.

PMID- 18708333
TI  - Mechanical analysis of the strains generated by water tension in plant stems.
      Part II: strains in wood and bark and apparent compliance.
AB  - Tree stems shrink in diameter during the day and swell during the night in
      response to changes in water tension in the xylem. Stem shrinkage can easily be
      measured in a nondestructive way, to derive continuous information about tree
      water status. The relationship between the strain and the change in water tension
      can be evaluated by empirical calibrations, or can be related to the structure of
      the plant. A mechanical analysis was performed to make this relationship
      explicit. The stem is modeled as a cylinder made of multiple layers of tissues,
      including heartwood, sapwood, and inner and outer bark. The effect of changes in
      water tension on the apparent strain at the surface of a tissue is quantified as
      a function of parameters defining stem anatomy and the mechanical properties of
      the tissues. Various possible applications in the context of tree physiology are
      suggested.

PMID- 18708334
TI  - Analyses of delta(13)C and delta(18)O in tree rings of Callitris columellaris
      provide evidence of a change in stomatal control of photosynthesis in response to
      regional changes in climate.
AB  - We examined relationships between stable isotopes of carbon (delta(13)C) and
      oxygen (delta(18)O) in tree rings of Callitris columellaris F. Muell in the semi
      arid Pilbara region of north-western Australia. To test the hypothesis that
      stomatal control of photosynthesis decreases during drier periods, we developed
      delta(13)C and delta(18)O chronologies spanning 1919-1999, and used a permutation
      regression approach to relate a 21-year running correlation between delta(13)C
      and delta(18)O to rainfall and temperature at Marble Bar and our study site. The
      relationship between delta(13)C and delta(18)O switched from being always
      negative before 1955 to being consistently positive after 1976, suggesting an
      increase in stomatal control of photosynthesis in recent decades. Changes in the
      delta(13)C-delta(18)O relationship reflected changes in rainfall, which has
      increased in the region by 30% since 1976. The correlation between delta(13)C and
      delta(18)O was positively related to the 21-year running mean of normalized
      rainfall anomalies at both the study site (P = 0.045, Adj. r(2) = 0.47) and
      Marble Bar (P = 0.046, Adj. r(2) = 0.48). In addition, the delta(13)C-delta(18)O
      correlation was negatively related (P = 0.047, Adj. r(2) = 0.61) to temperatures
      at Marble Bar. Our interpretation of the role of changes in climate affecting the
      relationship between tree-ring delta(13)C and delta(18)O is supported by evidence
      from the isotope composition of foliage samples: foliar delta(13)C and delta(18)O
      were negatively correlated with log stomatal conductance (delta(13)C, r = -0.41;
      delta(18)O, r = -0.42), whereas the correlation between foliar delta(13)C and
      delta(18)O was positive (r = 0.63, P = 0.027) after the summer wet period. Our
      data indicate that stomatal control of photosynthesis in Callitris adjusts to
      region-wide changes in climate and that, in a warmer and drier world, trees might
      adapt by increasing non-stomatal control of photosynthesis.

PMID- 18708335
TI  - Foliar delta(13)C and delta(18)O reveal differential physiological responses of
      canopy foliage to pre-planting weed control in a young spotted gum (Corymbia
      citriodora subsp. Variegata) plantation.
AB  - Weed control may improve the growth of forest plantations by influencing soil
      water and nutrient availability, but our knowledge of leaf-level physiological
      responses to weed control at different within-canopy positions is limited for
      tropical and subtropical plantations. Foliar carbon (delta(13)C) and oxygen
      (delta(18)O) isotope compositions, gas exchange, and nitrogen (N(mass)) and
      phosphorus (P(mass)) concentrations at four canopy positions were assessed in a
      young spotted gum (Corymbia citriodora subsp. Variegata (F. Muell.) A.R. Bean &
      M.W. McDonald) plantation subjected to either weed control or no weed control
      treatment, to test if leaves at different positions within the tree canopy had
      the same physiological responses to the weed control treatment. Weed control
      increased foliar delta(13)C but lowered delta(18)O in the upper-outer and upper
      inner canopy, indicating that weed control resulted in a higher foliar
      photosynthetic capacity at upper-canopy positions, a conclusion confirmed by gas
      exchange measurements. The increased photosynthetic capacity resulting from weed
      control can be explained by an increase in foliar N(mass). In the lower-outer
      canopy, weed control reduced foliar delta(13)C while lowering delta(18)O even
      more than in the upper-canopy, suggesting strong enhancement of the partial
      pressure of CO(2) in the leaf intercellular spaces and of foliar stomatal
      conductance in lower-canopy foliage. This conclusion was supported by gas
      exchange measurements. Foliar photosynthesis in the lower-inner canopy showed no
      significant response to weed control. The finding that leaves at different canopy
      positions differ in their physiological responses to weed control highlights the
      need to consider the canopy position effect when examining competition for soil
      nutrient and water resources between weeds and trees.

PMID- 18708336
TI  - Variations in growth, survival and carbon isotope composition (delta(13)C) among
      Pinus pinaster populations of different geographic origins.
AB  - To evaluate differences in growth and adaptability of maritime pine (Pinus
      pinaster Ait.), we studied growth, polycyclism, needle tissue carbon isotope
      composition (delta(13)C) as an estimate of water-use efficiency (WUE) and
      survival of seven populations at 10 years of age growing in a performance trial
      at a provenance test site in Escaroupim, Portugal. Six populations were from
      relatively high rainfall sites in Portugal and southwestern France (Atlantic
      group), and one population was from a more arid Mediterranean site in Spain.
      There were significant differences between some populations in total height,
      diameter at breast height, delta(13)C of bulk needle tissue, polycyclism and
      survival. A population from central Portugal (Leiria, on the Atlantic coast) was
      the tallest and had the lowest delta(13)C. Overall, the variation in delta(13)C
      was better explained by the mean minimum temperatures of the coldest month than
      by annual precipitation at the place of origin. Analyses of the relationships
      between delta(13)C and growth or survival revealed a distinct pattern for the
      Mediterranean population, with low delta(13)C (and WUE) associated with the
      lowest growth potential and reduced survival. There were significant negative
      correlations between delta(13)C and height or survival in the Atlantic group.
      Variation in polycyclism was correlated with annual precipitation at the place of
      origin. Some Atlantic populations maintained a high growth potential while
      experiencing moderate water stress. A detailed knowledge of the relationships
      between growth, survival and delta(13)C in contrasting environments will enhance
      our ability to select populations for forestry or conservation.

PMID- 18708337
TI  - Sapwood temperature gradients between lower stems and the crown do not influence
      estimates of stand-level stem CO(2) efflux.
AB  - Temperature plays a critical role in the regulation of respiration rates and is
      often used to scale measurements of respiration to the stand-level and calculate
      annual respiratory fluxes. Previous studies have indicated that failure to
      consider temperature gradients between sun-exposed stems and branches in the
      crown and shaded lower stems may result in errors when deriving stand-level
      estimates of stem CO(2) efflux. We measured vertical gradients in sapwood
      temperature in a mature lowland podocarp rain forest in New Zealand to: (1)
      estimate the effects of within-stem temperature variation on the vertical
      distribution of stem CO(2) efflux; and (2) use these findings to estimate stand
      level stem CO(2) efflux for this forest. Large within-stem gradients in sapwood
      temperature (1.6 +/- 0.1 to 6.0 +/- 0.5 degrees C) were observed. However, these
      gradients did not significantly influence the stand-level estimate of stem CO(2)
      efflux in this forest (536 +/- 42 mol CO(2) ha(-1) day(-1)) or the vertical
      distribution of stem CO(2) efflux, because of the opposing effects of daytime
      warming and nighttime cooling on CO(2) efflux in the canopy, and the small
      fraction of the woody biomass in the crowns of forest trees. Our findings suggest
      that detailed measurements of within-stand temperature gradients are unlikely to
      greatly improve the accuracy of tree- or stand-level estimates of stem CO(2)
      efflux.

PMID- 18708338
TI  - Changes during early development in photosynthetic light acclimation capacity
      explain the shade to sun transition in Nothofagus nitida.
AB  - Nothofagus nitida (Phil.) Krasser, an emergent tree of the Chilean evergreen
      forest, regenerates under the canopy. Nonetheless, it is common to find older
      saplings in clear areas. We hypothesized that this transition from shade to sun
      during the early developmental stages is made possible by an ontogenetic increase
      in the light acclimation capacity of photosynthesis. To test our hypothesis, we
      studied photosynthetic performance and photoprotection in N. nitida saplings at
      different developmental stages corresponding with three different height classes
      (short: 16.2 cm; medium-height: 48.0 cm; and tall: 73.7 cm) grown under
      contrasting light conditions (photosynthetic photon flux (PPF) of 20, 300 or 600
      micromol m(-2) s(-1)) until newly expanded leaves had developed. Light-saturated
      CO(2) assimilation rate and light compensation and saturation points increased
      with increasing PPF. Medium-height and tall saplings acclimated to high light had
      higher electron transport rates and higher proportions of open Photosystem II
      reaction centers than shorter plants acclimated to high light. Short saplings
      showed higher thermal dissipation and contents of xanthophylls than taller
      saplings. Only medium-height and tall saplings acclimated to high light recovered
      after photoinhibition. State transitions were higher in short plants growing in
      low light, and decreased with plant height and growth irradiance. Thus, during
      development, N. nitida changes the balance of light energy utilization and
      photoprotective mechanisms, supporting a phenotypic transition from shade to sun
      during its early ontogeny.

PMID- 18708339
TI  - Daily patterns of stem size variation in irrigated and unirrigated Eucalyptus
      globulus.
AB  - High resolution measurements of stem diameter variation provide a means to study
      short-term dynamics of tree growth and water status. In this 14-month study,
      daily changes in stem radius of Eucalyptus globulus Labill. seedlings were
      measured with electronic point dendrometers in a plantation in southern Tasmania,
      Australia. The daily patterns of stem expansion and shrinkage were classified
      into three phases: shrinkage; recovery; and increase in diameter from one maximum
      to the next, or increment. This study showed that rapid onset of even mild
      drought in irrigated trees caused distinct changes in daily patterns of stem
      diameter variation, particularly the duration of daily stem increment. The
      duration of the daily increment phase was directly related to increment
      magnitude. The dynamics of daily increment were significantly affected by mean
      minimum temperature, indicating a temperature limitation on metabolic processes
      underlying diameter growth in these trees. Most likely due to differences in
      conductance, the duration but not rate of the incremental daily expansion was
      greater in fast- than in slow-growing trees.

PMID- 18708340
TI  - Delayed soil thawing affects root and shoot functioning and growth in Scots pine.
AB  - In boreal regions, soil can remain frozen after the start of the growing season.
      We compared relationships between root characteristics and water relations in
      Scots pine (Pinus sylvestris L.) saplings subjected to soil frost treatments
      before and during the first week of the growing period in a controlled
      environment experiment. Delayed soil thawing delayed the onset of sap flow or
      totally blocked it if soil thawing lagged the start of the growing period by 7
      days. This effect was reflected in the electrical impedance of needles and trunks
      and in the relative electrolyte leakage of needles. Prolonged soil frost reduced
      or completely inhibited root growth. In unfrozen soil, limited trunk sap flow was
      observed despite unfavorable aboveground growing conditions (low temperature, low
      irradiance, short photoperiod). Following the earliest soil thaw, sap flow varied
      during the growing season, depending on light and temperature conditions,
      phenological stage of the plant and the amount of live needles in the canopy. The
      results suggest that delayed soil thawing can reduce tree growth, and if
      prolonged, it can be lethal.

PMID- 18708341
TI  - Size, shape and surface morphology of starch granules from Norway spruce needles
      revealed by transmission electron microscopy and atomic force microscopy: effects
      of elevated CO(2) concentration.
AB  - We compared the effects of ambient (350 ppm) and elevated CO(2) concentration
      (700 ppm) on the size and shape of starch granules in Norway spruce (Picea abies
      (L.) Karst.) needles during one growing season. Starch granules were isolated
      from needles by alkaline digestion and analyzed by transmission electron
      microscopy (TEM) and atomic force microscopy (AFM). Measurements made with a
      particle size analyzer indicated that starch granules ranged between 0.5 and 10
      microm. Granule size and shape varied according to needle developmental stage and
      CO(2) concentration. Generally, elevated CO(2) concentration increased the size
      of the starch granules. Fine surface structures (< 10 nm in size) studied by AFM
      were characterized by the presence of protrusions, furrows and pores.

PMID- 18708342
TI  - Selective distribution of protein kinase A regulatory subunit RII{alpha} in
      rodent gliomas.
AB  - Differential diagnosis of brain tumor types is mainly based on cell morphology
      and could benefit from additional markers. The cAMP second-messenger system is
      involved in regulating cell proliferation and differentiation and is conceivably
      modulated during cancer transformation. The cAMP second-messenger system mainly
      activates protein kinases, which are in part docked to cytoskeleton, membranes,
      or organelles by anchoring proteins, forming protein aggregates that are
      detergent insoluble and not freely diffusible and that are characteristic for
      each cell type. The intracellular distribution of the detergent-insoluble
      regulatory subunits (R) of the cAMP-dependent protein kinase has been examined in
      mouse and rat glioma cells both in vitro and in vivo by immunohistochemistry. In
      normal rodent brains, the RIIalpha regulatory subunit is detergent insoluble only
      in ependymal cells, while in the rest of the brain it is present in soluble form.
      Immunohistochemistry shows that in both mouse and rat glioma cell lines, RIIalpha
      is mainly detergent insoluble. RIIalpha is localized close to the nucleus,
      associated with smooth vesicles in the trans-Golgi network area. Both paclitaxel
      and vinblastine cause a redistribution of RIIalpha within the cell. Under
      conditions that increased intracellular cAMP, apoptosis of glioma cells was
      observed, and it was accompanied by RIIalpha redistribution. Also in vivo,
      detergent-insoluble RIIalpha can be observed in mouse and rat gliomas, where it
      delineates the border between normal brain tissue and glioma. Therefore,
      intracellular distribution of detergent-insoluble RIIalpha can assist in
      detecting tumor cells within the brain, thus making the histologic diagnosis of
      brain tumors more accurate, and may represent an additional target for therapy.

PMID- 18708343
TI  - Prognostic factors and outcomes in patients with leptomeningeal melanomatosis.
AB  - The purpose of this study was to describe a cohort of patients with
      leptomeningeal melanomatosis (LM) and to determine prognostic factors for
      outcomes in these patients. The primary hypothesis was that more extensive burden
      of CNS metastasis at the time of diagnosis of LM (as evidenced by imaging of the
      CNS parenchyma and meninges and cerebrospinal fluid [CSF] cytology status
      [positive versus negative]) correlates with poorer outcomes. The records of all
      patients with LM treated at M. D. Anderson Cancer Center between 1944 and 2002
      were reviewed. Information on clinical course and outcomes was gathered.
      Univariate and multivariate analyses were performed on 110 patients using Cox
      proportional hazards regression analysis to examine the effects of possible
      predictive factors on survival. The overall median survival from LM diagnosis was
      10 weeks, with a 95% confidence interval (CI) of 8-14 weeks. Eighty-six (78.2%)
      patients had cutaneous primary lesions, and 23 (20.9%) had melanoma of unknown
      primary site. The primary hypothesis was not proven. Neither the presence of
      parenchymal CNS metastases, nor greater imaging evidence of LM, nor positive CSF
      cytology at diagnosis correlated with survival outcomes. Univariate analyses
      revealed possible predictors of longer survival, including the presence of
      supratentorial or spinal LM on imaging at diagnosis versus its absence and any
      treatment of LM, whereas elevated serum lactate dehydrogenase at the time of LM
      diagnosis predicted shorter survival. Multivariate analysis revealed that a
      history of a primary melanoma lesion originating on the trunk predicted shorter
      survival after LM diagnosis (hazard ratio [HR] = 2.0, 95% CI = 1.0-3.8, p =
      0.035), and treatment with intrathecal chemotherapy predicted longer survival (HR
      = 0.5, 95% CI = 0.4-0.8, p = 0.0036). The positive result with respect to
      treatment is unreliable due to the inability to remove treatment selection bias
      from the analysis. This retrospective analysis confirmed the dismal prognosis
      associated with LM. The amount of CNS tumor burden at the time of diagnosis of LM
      did not inversely correlate with survival outcomes, contrary to our hypothesis.

PMID- 18708344
TI  - VEGF Trap induces antiglioma effect at different stages of disease.
AB  - Pathological angiogenesis is a hallmark of cancer, specifically of glioblastomas,
      the most malignant and common primary brain tumor. Vascular endothelial growth
      factor (VEGF) is the key protein in the regulation of the hypervascular phenotype
      of primary malignant brain tumors. In this study, we tested VEGF Trap, a soluble
      decoy receptor for VEGF, in an intracranial glioma model. VEGF Trap was
      administered in short or prolonged schedules to animals bearing human gliomas at
      different stages of disease. Of importance, VEGF Trap treatment was efficacious
      in both initial and advanced phases of tumor development by significantly
      increasing overall survival. Furthermore, this effect was enhanced in animals
      treated with more prolonged regimens. In addition, we observed the emergence of a
      VEGF Trap-resistant phenotype characterized by tumor growth and increased
      invasiveness. Our results suggest that VEGF Trap will be effective in treating
      both patients with recurrent or progressive resectable glioblastoma and patients
      that have undergone extensive initial surgery. Finally, our results indicate that
      the clinical success of VEGF Trap may depend on a prolonged treatment in combined
      therapy aiming to simultaneously inhibit angiogenesis and tumor invasion.

PMID- 18708345
TI  - Inhibition of heparan sulfate and chondroitin sulfate proteoglycan biosynthesis.
AB  - Proteoglycans (PGs) are composed of a protein moiety and a complex
      glycosaminoglycan (GAG) polysaccharide moiety. GAG chains are responsible for
      various biological activities. GAG chains are covalently attached to serine
      residues of the core protein. The first step in PG biosynthesis is xylosylation
      of certain serine residues of the core protein. A specific linker tetrasaccharide
      is then assembled and serves as an acceptor for elongation of GAG chains. If the
      production of endogenous GAG chains is selectively inhibited, one could determine
      the role of these endogenous molecules in physiological and developmental
      functions in a spatiotemporal manner. Biosynthesis of PGs is often blocked with
      the aid of nonspecific agents such as chlorate, a bleaching agent, and brefeldin
      A, a fungal metabolite, to elucidate the biological roles of GAG chains.
      Unfortunately, these agents are highly lethal to model organisms. Xylosides are
      known to prime GAG chains. Therefore, we hypothesized that modified xylose
      analogs may able to inhibit the biosynthesis of PGs. To test this, we synthesized
      a library of novel 4-deoxy-4-fluoroxylosides with various aglycones using click
      chemistry and examined each for its ability to inhibit heparan sulfate and
      chondroitin sulfate using Chinese hamster ovary cells as a model cellular system.

PMID- 18708346
TI  - Metabolic stress induces the lysosomal degradation of neuropilin-1 but not
      neuropilin-2.
AB  - The neuropilins-1 and -2 (NRP1 and NRP2) function as receptors for both the
      semaphorins and vascular endothelial growth factor. In addition to their
      contribution to the development of the nervous system, NRP1 and NRP2 have been
      implicated in angiogenesis and tumor progression. Given their importance to
      cancer and endothelial biology and their potential as therapeutic targets, an
      important issue that has not been addressed is the impact of metabolic stress
      conditions characteristic of the tumor microenvironment on their expression and
      function. Here, we demonstrate that hypoxia and nutrient deprivation stimulate
      the rapid loss of NRP1 expression in both endothelial and carcinoma cells. NRP2
      expression, in contrast, is maintained under these conditions. The lysosomal
      inhibitors chloroquine and bafilomycin A1 prevented the loss of NRP1 expression,
      but proteasomal inhibitors had no effect. The hypothesis that NRP1 is degraded by
      autophagy is supported by the findings that its expression is lost rapidly in
      response to metabolic stress, prevented with 3-methyladenine and induced by
      rapamycin. Targeted depletion of NRP2 using small hairpin RNA revealed that NRP2
      can function in the absence of NRP1 to mediate endothelial tube formation in
      hypoxia. Studies aimed at assessing NRP function and targeted therapy in cancer
      and angiogenesis should consider the impact of metabolic stress.

PMID- 18708347
TI  - Crystal structure and NMR binding reveal that two small molecule antagonists
      target the high affinity ephrin-binding channel of the EphA4 receptor.
AB  - The Eph receptor tyrosine kinases regulate a variety of physiological and
      pathological processes not only during development but also in adult organs, and
      therefore they represent a promising class of drug targets. The EphA4 receptor
      plays important roles in the inhibition of the regeneration of injured axons,
      synaptic plasticity, platelet aggregation, and likely in certain types of cancer.
      Here we report the first crystal structure of the EphA4 ligand-binding domain,
      which adopts the same jellyroll beta-sandwich architecture as shown previously
      for EphB2 and EphB4. The similarity with EphB receptors is high in the core beta
      stranded regions, whereas large variations exist in the loops, particularly the D
      E and J-K loops, which form the high affinity ephrin binding channel. We also
      used isothermal titration calorimetry, NMR spectroscopy, and computational
      docking to characterize the binding to EphA4 of two small molecules, 4- and 5
      (2,5 dimethyl-pyrrol-1-yl)-2-hydroxybenzoic acid which antagonize ephrin-induced
      effects in EphA4-expressing cells. We show that the two molecules bind to the
      EphA4 ligand-binding domain with K(d) values of 20.4 and 26.4 microm,
      respectively. NMR heteronuclear single quantum coherence titrations revealed that
      upon binding, both molecules significantly perturb EphA4 residues Ile(31)-Met(32)
      in the D-E loop, Gln(43) in the E beta-strand, and Ile(131)-Gly(132) in the J-K
      loop. Molecular docking shows that they can occupy a cavity in the high affinity
      ephrin binding channel of EphA4 in a similar manner, by interacting mainly with
      the EphA4 residues in the E strand and D-E and J-K loops. However, many of the
      interactions observed in Eph receptor-ephrin complexes are absent, which is
      consistent with the small size of the two molecules and may account for their
      relatively weak binding affinity. Thus, our studies provide the first published
      structure of the ligand-binding domain of an EphA receptor of the A subclass.
      Furthermore, the results demonstrate that the high affinity ephrin binding
      channel of the Eph receptors is amenable to targeting with small molecule
      antagonists and suggest avenues for further optimization.

PMID- 18708348
TI  - RNA editing of androgen receptor gene transcripts in prostate cancer cells.
AB  - Reactivation of the androgen receptor (AR) signaling pathway represents a
      critical step in the growth and survival of androgen-independent (AI) prostate
      cancer (CaP). In this study we show the DU145 and PC3 AI human CaP cell lines
      respond to androgens and require AR expression for optimal proliferation in
      vitro. Interestingly, AR gene transcripts in DU145 and PC3 cells harbored a large
      number of single base pair nucleotide transitions that resulted in missense
      mutations in selected AR codons. The most notable lesion detected in AR gene
      transcripts included the oncogenic codon 877T-->A gain-of-function mutation.
      Surprisingly, AR gene transcript nucleotide transitions were not genome-encoded
      substitutions, but instead the mutations co-localized to putative A-to-I, U-to-C,
      C-to-U, and G-to-A RNA editing sites, suggesting the lesions were mediated
      through RNA editing mechanisms. Higher levels of mRNA encoding the A-to-I RNA
      editing enzymes ADAR1 and ADARB1 were observed in DU145 and PC3 cells relative to
      the androgen-responsive LNCaP and 22Rv1 human CaP cell lines, which correlated
      with higher levels of AR gene transcript A-to-I editing detected in DU145 and PC3
      cells. Our results suggest that AR gene transcripts are targeted by different RNA
      editing enzymes in DU145 and PC3 cells. Thus RNA editing of AR gene transcripts
      may contribute to the etiology of hormone-refractory phenotypes in advanced stage
      AI CaP.

PMID- 18708349
TI  - Discovery of cellular regulation by protein degradation.

PMID- 18708350
TI  - Menaquinone as well as ubiquinone as a bound quinone crucial for catalytic
      activity and intramolecular electron transfer in Escherichia coli membrane-bound
      glucose dehydrogenase.
AB  - Escherichia coli membrane-bound glucose dehydrogenase (mGDH), which is one of
      quinoproteins containing pyrroloquinoline quinone (PQQ) as a coenzyme, is a good
      model for elucidating the function of bound quinone inside primary dehydrogenases
      in respiratory chains. Enzymatic analysis of purified mGDH from cells defective
      in synthesis of ubiquinone (UQ) and/or menaquinone (MQ) revealed that Q-free mGDH
      has very low levels of activity of glucose dehydrogenase and UQ2 reductase
      compared with those of UQ-bearing mGDH, and both activities were significantly
      increased by reconstitution with UQ1. On the other hand, MQ-bearing mGDH retains
      both catalytic abilities at the same levels as those of UQ-bearing mGDH. A
      radiolytically generated hydrated electron reacted with the bound MQ to form a
      semiquinone anion radical with an absorption maximum at 400 nm. Subsequently,
      decay of the absorbance at 400 nm was accompanied by an increase in the
      absorbance at 380 nm with a first order rate constant of 5.7 x 10(3) s(-1). This
      indicated that an intramolecular electron transfer from the bound MQ to the PQQ
      occurred. EPR analysis revealed that characteristics of the semiquinone radical
      of bound MQ are similar to those of the semiquinone radical of bound UQ and
      indicated an electron flow from PQQ to MQ as in the case of UQ. Taken together,
      the results suggest that MQ is incorporated into the same pocket as that for UQ
      to perform a function almost equivalent to that of UQ and that bound quinone is
      involved at least partially in the catalytic reaction and primarily in the
      intramolecular electron transfer of mGDH.

PMID- 18708351
TI  - MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting
      p27Kip1.
AB  - We explored the role of microRNAs (miRNAs) in acquiring resistance to tamoxifen,
      a drug successfully used to treat women with estrogen receptor-positive breast
      cancer. miRNA microarray analysis of MCF-7 cell lines that are either sensitive
      (parental) or resistant (4-hydroxytamoxifen-resistant (OHT(R))) to tamoxifen
      showed significant (>1.8-fold) up-regulation of eight miRNAs and marked down
      regulation (>50%) of seven miRNAs in OHT(R) cells compared with parental MCF-7
      cells. Increased expression of three of the most promising up-regulated (miR-221,
      miR-222, and miR-181) and down-regulated (miR-21, miR-342, and miR-489) miRNAs
      was validated by real-time reverse transcription-PCR. The expression of miR-221
      and miR-222 was also significantly (2-fold) elevated in HER2/neu-positive primary
      human breast cancer tissues that are known to be resistant to endocrine therapy
      compared with HER2/neu-negative tissue samples. Ectopic expression of miR-221/222
      rendered the parental MCF-7 cells resistant to tamoxifen. The protein level of
      the cell cycle inhibitor p27(Kip1), a known target of miR-221/222, was reduced by
      50% in OHT(R) cells and by 28-50% in miR-221/222-overexpressing MCF-7 cells.
      Furthermore, overexpression of p27(Kip1) in the resistant OHT(R) cells caused
      enhanced cell death when exposed to tamoxifen. This is the first study
      demonstrating a relationship between miR-221/222 expression and HER2/neu
      overexpression in primary breast tumors that are generally resistant to tamoxifen
      therapy. This finding also provides the rationale for the application of altered
      expression of specific miRNAs as a predictive tamoxifen-resistant breast cancer
      marker.

PMID- 18708352
TI  - Amino acids induce peptide uptake via accelerated degradation of CUP9, the
      transcriptional repressor of the PTR2 peptide transporter.
AB  - Multiple pathways link expression of PTR2, the transporter of di- and tripeptides
      in the yeast Saccharomyces cerevisiae, to the availability and quality of
      nitrogen sources. Previous work has shown that induction of PTR2 by extracellular
      amino acids requires, in particular, SSY1 and PTR3. SSY1 is structurally similar
      to amino acid transporters but functions as a sensor of amino acids. PTR3 acts
      downstream of SSY1. Expression of the PTR2 peptide transporter is induced not
      only by amino acids but also by dipeptides with destabilizing N-terminal
      residues. These dipeptides bind to UBR1, the ubiquitin ligase of the N-end rule
      pathway, and allosterically accelerate the UBR1-dependent degradation of CUP9, a
      transcriptional repressor of PTR2. UBR1 targets CUP9 through its internal degron.
      Here we demonstrate that the repression of PTR2 by CUP9 requires TUP1 and SSN6,
      the corepressor proteins that form a complex with CUP9. We also show that the
      induction of PTR2 by amino acids is mediated by the UBR1-dependent acceleration
      of CUP9 degradation that requires both SSY1 and PTR3. The acceleration of CUP9
      degradation is shown to be attained without increasing the activity of the N-end
      rule pathway toward substrates with destabilizing N-terminal residues. We also
      found that GAP1, a general amino acid transporter, strongly contributes to the
      induction of PTR2 by Trp. Although several aspects of this complex circuit remain
      to be understood, our findings establish new functional links between the amino
      acids-sensing SPS system, the CUP9-TUP1-SSN6 repressor complex, the PTR2 peptide
      transporter, and the UBR1-dependent N-end rule pathway.

PMID- 18708353
TI  - Detection of lipid domains in model and cell membranes by fluorescence lifetime
      imaging microscopy of fluorescent lipid analogues.
AB  - The presence of lipid domains in cellular membranes and their characteristic
      features are still an issue of dividing discussion. Several recent studies
      implicate lipid domains in plasma membranes of mammalian cells as short lived and
      in the submicron range. Measuring the fluorescence lifetime of appropriate lipid
      analogues is a proper approach to detect domains with such properties. Here, the
      sensitivity of the fluorescence lifetime of1-palmitoyl-2-[6-[(7-nitro-2-1,3
      benzoxadiazol-4-yl)amino]-hexanoyl]-sn-glycero-3-phospholipid (C6-NBD
      phospholipid) analogues has been employed to characterize lipid domains in giant
      unilamellar vesicles (GUVs) and the plasma membrane of mammalian cells by
      fluorescence lifetime imaging (FLIM). Fluorescence decay of C6-NBD
      phosphatidylcholine is characterized by a short and long lifetime. For GUVs
      forming microscopically visible lipid domains the longer lifetime in the liquid
      disordered (ld) and the liquid ordered (lo) phase was clearly distinct, being
      approximately 7 ns and 11 ns, respectively. Lifetimes were not sensitive to
      variation of cholesterol concentration of domain-forming GUVs indicating that the
      lipid composition and physical properties of those lipid domains are well defined
      entities. Even the existence of submicroscopic domains can be detected by FLIM as
      demonstrated for GUVs of palmitoyloleoyl phosphatidylcholine/N-palmitoyl-d
      sphingomyelin/cholesterol mixtures. A broad distribution of the long lifetime was
      found for C6-NBD-phosphatidylcholine inserted in the plasma membrane of HepG2 and
      HeLa cells centered around 11 ns. FLIM studies on lipid domains forming giant
      vesicles derived from the plasma membrane of HeLa cells may suggest that a
      variety of submicroscopic lipid domains exists in the plasma membrane of intact
      cells.

PMID- 18708354
TI  - The Rtt106 histone chaperone is functionally linked to transcription elongation
      and is involved in the regulation of spurious transcription from cryptic
      promoters in yeast.
AB  - Rtt106 is a histone chaperone that has been suggested to play a role in
      heterochromatin-mediated silencing in Saccharomyces cerevisiae. It interacts
      physically and functionally with the chromatin assembly factor-1 (CAF-1), which
      is associated with replication-coupled nucleosomal deposition. In this work, we
      have taken several approaches to study Rtt106 in greater detail and have
      identified a previously unknown function of Rtt106. We found genetic interactions
      between rtt106Delta and mutations in genes encoding transcription elongation
      factors, including Spt6, TFIIS, and members of the PAF and yeast DSIF complexes.
      In addition, chromatin immunoprecipitation analysis indicates that Rtt106 is
      associated with transcribed regions of active genes. Furthermore, our results
      show that Rtt106 is required for the repression of transcription from a cryptic
      promoter within a coding region. This observation strongly suggests that Rtt106
      is involved in the regulation of chromatin structure of transcribed regions.
      Finally, we provide evidence that Rtt106 plays a role in regulating the levels of
      histone H3 transcription-coupled deposition over transcribed regions. Taken
      together, our results indicate a direct link for Rtt106 with transcription
      elongation and the chromatin dynamics associated with RNA polymerase II passage.

PMID- 18708355
TI  - Characterization of the tautomycin biosynthetic gene cluster from Streptomyces
      spiroverticillatus unveiling new insights into dialkylmaleic anhydride and
      polyketide biosynthesis.
AB  - Tautomycin (TTM) is a highly potent and specific protein phosphatase inhibitor
      isolated from Streptomyces spiroverticillatus. The biological activity of TTM
      makes it an important lead for drug discovery, whereas its spiroketal-containing
      polyketide chain and rare dialkylmaleic anhydride moiety draw attention to novel
      biosynthetic chemistries responsible for its production. To elucidate the
      biosynthetic machinery associated with these novel molecular features, the ttm
      biosynthetic gene cluster from S. spiroverticillatus was isolated and
      characterized, and its involvement in TTM biosynthesis was confirmed by gene
      inactivation and complementation experiments. The ttm cluster was localized to a
      86-kb DNA region, consisting of 20 open reading frames that encode three modular
      type I polyketide synthases (TtmHIJ), one type II thioesterase (TtmT), five
      proteins for methoxymalonyl-S-acyl carrier protein biosynthesis (Ttm-ABCDE),
      eight proteins for dialkylmaleic anhydride biosynthesis and regulation
      (TtmKLMNOPRS), as well as two additional regulatory proteins (TtmF and TtmQ) and
      one tailoring enzyme (TtmG). A model for TTM biosynthesis is proposed based on
      functional assignments from sequence analysis, which agrees well with previous
      feeding experiments, and has been further supported by in vivo gene inactivation
      experiments. These findings set the stage to fully investigate TTM biosynthesis
      and to biosynthetically engineer new TTM analogs.

PMID- 18708356
TI  - Small ubiquitin-related modifier (SUMO) binding determines substrate recognition
      and paralog-selective SUMO modification.
AB  - Small ubiquitin-related modifiers (SUMOs) regulate diverse cellular processes
      through their covalent attachment to target proteins. Vertebrates express three
      SUMO paralogs: SUMO-1, SUMO-2, and SUMO-3 (SUMO-2 and SUMO-3 are approximately
      96% identical and referred to as SUMO-2/3). SUMO-1 and SUMO-2/3 are conjugated,
      at least in part, to unique subsets of proteins and thus regulate distinct
      cellular pathways. However, how different proteins are selectively modified by
      SUMO-1 and SUMO-2/3 is unknown. We demonstrate that BLM, the RecQ DNA helicase
      mutated in Bloom syndrome, is preferentially modified by SUMO-2/3 both in vitro
      and in vivo. Our findings indicate that non-covalent interactions between SUMO
      and BLM are required for modification at non-consensus sites and that
      preferential SUMO-2/3 modification is determined by preferential SUMO-2/3
      binding. We also present evidence that sumoylation of a C-terminal fragment of
      HIPK2 is dependent on SUMO binding, indicating that non-covalent interactions
      between SUMO and target proteins provide a general mechanism for SUMO substrate
      selection and possible paralog-selective modification.

PMID- 18708357
TI  - A novel splicing variant of mouse interleukin (IL)-24 antagonizes IL-24-induced
      apoptosis.
AB  - Alternative splicing of mRNA enables functionally diverse protein isoforms to be
      expressed from a single gene, allowing transcriptome diversification. Interleukin
      (IL)-24/MDA-7 is a member of the IL-10 gene family, and FISP (IL-4-induced
      secreted protein), its murine homologue, is selectively expressed and secreted by
      T helper 2 lymphocytes. A novel splice variant of mouse IL-24/FISP, designated
      FISP-sp, lacks 29 nucleotides from the 5'-end of exon 4 of FISP. The level of
      FISP-sp expression is 10% of the level of total primary FISP transcription.
      Unlike FISP, FISP-sp does not induce growth inhibition and apoptosis. FISP-sp is
      exclusively localized in endoplasmic reticulum, and its expression is up
      regulated by endoplasmic reticulum stress. Our results suggest that the novel
      splicing variant FISP-sp dimerizes with FISP and blocks its secretion and
      inhibits FISP-induced apoptosis in vivo.

PMID- 18708358
TI  - Cadherin-11 promotes the metastasis of prostate cancer cells to bone.
AB  - Bone is the most common site of metastases from prostate cancer. The mechanism by
      which prostate cancer cells metastasize to bone is not fully understood, but
      interactions between prostate cancer cells and bone cells are thought to initiate
      the colonization of metastatic cells at that site. Here, we show that cadherin-11
      (also known as osteoblast-cadherin) was highly expressed in prostate cancer cell
      line derived from bone metastases and had strong homophilic binding to
      recombinant cadherin-11 in vitro. Down-regulation of cadherin-11 in bone
      metastasis-derived PC3 cells with cadherin-11-specific short hairpin RNA (PC3
      shCad-11) significantly decreased the adhesion of those cells to cadherin-11 in
      vitro. In a mouse model of metastasis, intracardiac injection of PC3 cells led to
      metastasis of those cells to bone. However, the incidence of PC3 metastasis to
      bone in this model was reduced greatly when the expression of cadherin-11 by
      those cells was silenced. The clinical relevance of cadherin-11 in prostate
      cancer metastases was further studied by examining the expression of cadherin-11
      in human prostate cancer specimens. Cadherin-11 was not expressed by normal
      prostate epithelial cells but was detected in prostate cancer, with its
      expression increasing from primary to metastatic disease in lymph nodes and
      especially bone. Cadherin-11 expression was not detected in metastatic lesions
      that occur in other organs. Collectively, these findings suggest that cadherin-11
      is involved in the metastasis of prostate cancer cells to bone.

PMID- 18708360
TI  - Chemokine decoy receptor d6 plays a negative role in human breast cancer.
AB  - Chemokine binding protein D6 is a promiscuous decoy receptor that can inhibit
      inflammation in vivo; however, the role it plays in cancer is not well known yet.
      In this study, we showed for the first time that human breast cancer
      differentially expressed D6 and the expression could be regulated by some
      cytokines. More importantly, overexpression of D6 in human breast cancer cells
      inhibits proliferation and invasion in vitro and tumorigenesis and lung
      metastasis in vivo. This inhibition is associated with decreased chemokines
      (e.g., CCL2 and CCL5), vessel density, and tumor-associated macrophage
      infiltration. Furthermore, D6 expression is inversely correlated to lymph node
      metastasis as well as clinical stages, but positively correlated to disease-free
      survival rate in cancer patients. Therefore, D6 plays a negative role in the
      growth and metastasis of breast cancer.

PMID- 18708359
TI  - Stress chaperone GRP78/BiP confers chemoresistance to tumor-associated
      endothelial cells.
AB  - The tumor vasculature is essential for tumor growth and survival and is a key
      target for anticancer therapy. Glioblastoma multiforme, the most malignant form
      of brain tumor, is highly vascular and contains abnormal vessels, unlike blood
      vessels in normal brain. Previously, we showed that primary cultures of human
      brain endothelial cells, derived from blood vessels of malignant glioma tissues
      (TuBEC), are physiologically and functionally different from endothelial cells
      derived from nonmalignant brain tissues (BEC) and are substantially more
      resistant to apoptosis. Resistance of TuBEC to a wide range of current anticancer
      drugs has significant clinical consequences as it represents a major obstacle
      toward eradication of residual brain tumor. We report here that the endoplasmic
      reticulum chaperone GRP78/BiP is generally highly elevated in the vasculature
      derived from human glioma specimens, both in situ in tissue and in vitro in
      primary cell cultures, compared with minimal GRP78 expression in normal brain
      tissues and blood vessels. Interestingly, TuBEC constitutively overexpress GRP78
      without concomitant induction of other major unfolded protein response targets.
      Resistance of TuBEC to chemotherapeutic agents such as CPT-11, etoposide, and
      temozolomide can be overcome by knockdown of GRP78 using small interfering RNA or
      chemical inhibition of its catalytic site. Conversely, overexpression of GRP78 in
      BEC rendered these cells resistant to drug treatments. Our findings provide the
      proof of principle that targeting GRP78 will sensitize the tumor vasculature to
      chemotherapeutic drugs, thus enhancing the efficacy of these drugs in combination
      therapy for glioma treatment.

PMID- 18708361
TI  - c-Jun Is critical for the progression of osteosarcoma: proof in an orthotopic
      spontaneously metastasizing model.
AB  - The oncogene c-Jun has been found to be up-regulated in a variety of cancers
      including osteosarcoma. DNA enzymes (DNAzymes) are oligonucleotides capable of
      specific catalysis of target mRNA. A c-Jun DNAzyme inhibited the growth and
      metastasis of osteosarcoma in an orthotopic spontaneously metastasizing model of
      the disease. c-Jun down-regulation-mediated apoptosis in osteosarcoma cells
      involved caspase-1, caspase-2, and caspase-8, but not the Fas/FasL pathway.
      Clinically, knockdown of c-Jun with DNAzymes may proffer an improved treatment
      outcome for these tumors originating in bone.

PMID- 18708363
TI  - Protein sialylation by sialyltransferase involves radiation resistance.
AB  - Previously, we identified beta-galactoside alpha(2,6)-sialyltransferase (ST6Gal
      I) as a candidate biomarker for ionizing radiation. The expression of ST6Gal I
      and the level of protein sialylation increased following radiation exposure in a
      dose-dependent manner. Radiation induced ST6Gal I cleavage and the cleaved form
      of ST6Gal I was soluble and secreted. Sialylation of integrin beta1, a
      glycosylated cell surface protein, was stimulated by radiation exposure and this
      increased its stability. Overexpression of ST6Gal I in SW480 colon cancer cells
      that initially showed a low level of ST6Gal I expression increased the
      sialylation of integrin beta1 and also increased the stability of the protein.
      Inhibition of sialylation by transfection with neuraminidase 2 or neuraminidase 3
      or by treatment with short interfering RNA targeting ST6Gal I reversed the
      effects of ST6Gal I overexpression. In addition, ST6Gal I overexpression
      increased clonogenic survival following radiation exposure and reduced radiation
      induced cell death and caspase 3 activation. However, removal of sialic acids by
      neuraminidase 2 or knockdown of expression by short interfering RNA targeting
      ST6Gal I restored radiation-induced cell death phenotypes. In conclusion,
      radiation exposure was found to increase the sialylation of glycoproteins such as
      integrin beta1 by inducing the expression of ST6Gal I, and increased protein
      sialylation contributed to cellular radiation resistance.

PMID- 18708364
TI  - Cross-talk between aryl hydrocarbon receptor and mitogen-activated protein kinase
      signaling pathway in liver cancer through c-raf transcriptional regulation.
AB  - c-raf is a serine-threonine kinase and a downstream effector of ras signaling.
      This kinase plays an essential role in cell proliferation, differentiation, and
      apoptosis. In the past, we reported induction of c-raf gene expression in rat
      liver cancer on treatment with a mixture of aryl hydrocarbon receptor (AhR)
      agonists. This prompted our interest in investigating the role of AhR in the
      transcriptional regulation of c-raf. Initially, we cloned the rat c-raf promoter
      and sequenced the genomic DNA and cDNA by Southern blotting and capillary
      electrophoresis. Then, a genetic algorithm was applied to search for putative AhR
      binding sites. DNA-binding activity of AhR was confirmed by electromobility shift
      assay. We also studied c-raf gene expression in rat hepatoma cell lines with
      functional and/or devoid AhR and in primary human and rat hepatocyte cultures.
      Overall, we identified five and three AhR-binding sites in the human and rat c
      raf gene, respectively. Treatment of hepatocyte cultures with the AhR antagonist
      resveratrol reduced DNA binding of AhR. Only rat hepatoma cells with functional
      AhR responded to 1 nmol/L 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment with >10
      fold c-raf mRNA induction. Treatment of human and rat hepatocyte cultures with
      various AhR-activating chemicals resulted in induction of c-raf gene expression,
      albeit at different levels. Taken collectively, we show AhR to be a master
      regulator of c-raf and propose cross-talk between AhR and the mitogen-activated
      protein kinase signaling pathway in chemically induced hepatocarcinogenesis.

PMID- 18708362
TI  - Alternative splicing and caspase-mediated cleavage generate antagonistic variants
      of the stress oncoprotein LEDGF/p75.
AB  - There is increasing evidence that an augmented state of cellular oxidative stress
      modulates the expression of stress genes implicated in diseases associated with
      health disparities such as certain cancers and diabetes. Lens epithelium-derived
      growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, is emerging as a
      survival oncoprotein that promotes resistance to oxidative stress-induced cell
      death and chemotherapy. We previously showed that LEDGF/p75 is targeted by
      autoantibodies in prostate cancer patients and is overexpressed in prostate
      tumors, and that its stress survival activity is abrogated during apoptosis.
      LEDGF/p75 has a COOH-terminally truncated splice variant, p52, whose role in
      stress survival and apoptosis has not been thoroughly investigated. We observed
      unbalanced expression of these proteins in a panel of tumor cell lines, with
      LEDGF/p75 generally expressed at higher levels. During apoptosis, caspase-3
      cleaved p52 to generate a p38 fragment that lacked the NH(2)-terminal PWWP domain
      and failed to transactivate the Hsp27 promoter in reporter assays. However, p38
      retained chromatin association properties and repressed the transactivation
      potential of LEDGF/p75. Overexpression of p52 or its variants with truncated PWWP
      domains in several tumor cell lines induced apoptosis, an activity that was
      linked to the presence of an intron-derived COOH-terminal sequence. These results
      implicate the PWWP domain of p52 in transcription function but not in chromatin
      association and proapoptotic activities. Consistent with their unbalanced
      expression in tumor cells, LEDGF/p75 and p52 seem to play antagonistic roles in
      the cellular stress response and could serve as targets for novel antitumor
      therapies.

PMID- 18708365
TI  - Effects of palifermin on antitumor activity of chemotherapeutic and biological
      agents in human head and neck and colorectal carcinoma xenograft models.
AB  - Damage to the gastrointestinal mucosa is a common dose-limiting toxicity of
      several anticancer therapies. Until recently, adequate control of oral mucositis
      was considered a significant unmet medical need, with most available treatments
      providing only palliative benefits without protecting the gastrointestinal
      epithelium from the damaging effects of cancer therapy. In 2005, palifermin
      [recombinant human keratinocyte growth factor (KGF)] was approved to decrease the
      incidence and duration of severe oral mucositis in patients with hematologic
      malignancies receiving myelotoxic therapy requiring hematopoietic stem cell
      support. Current trials are investigating the use of palifermin in solid tumor
      settings. The objective of this study was to determine whether combining
      palifermin with different chemotherapeutic or biological agents affected the
      antitumor activity of these agents in human head and neck (FaDu) and colorectal
      (HT29) carcinoma xenograft models. Nude CD1 mice were injected with 1 x 10(7) of
      either FaDu or HT29 cells, which express both KGF and epithelial growth factor
      receptors. Animals were treated with palifermin in various combinations with
      chemotherapeutic (5-fluorouracil and cisplatin) and/or biological (bevacizumab,
      cetuximab, and panitumumab) agents. Palifermin alone had no effect on either FaDu
      or HT29 tumor growth. Palifermin did not affect the therapeutic efficacy of 5
      fluorouracil, cisplatin, cetuximab, bevacizumab, or panitumumab in any of the two
      or three-way drug combinations tested in either model. The results of this study
      showed that palifermin did not promote the growth of two carcinoma cell lines
      that express functional KGF receptors and did not protect these tumor cells from
      the antitumor effects of several chemotherapeutic and biological agents.

PMID- 18708366
TI  - Wilms' tumor 1 suppressor gene mediates antiestrogen resistance via down
      regulation of estrogen receptor-alpha expression in breast cancer cells.
AB  - The antiestrogen tamoxifen has been used in the treatment of hormone-responsive
      breast cancer for over a decade. The loss of estrogen receptor (ER) expression is
      the most common mechanism for de novo antiestrogen resistance. Wilms' tumor 1
      suppressor gene (WT1) is a clinically useful marker that is associated with poor
      prognosis in breast cancer patients; its high level expression is frequently
      observed in cases of breast cancer that are estrogen and progesterone receptor
      negative. The lack of expression of these receptors is characteristic of tumor
      cells that are not responsive to hormonal manipulation. To determine whether
      there is a linkage between WT1 expression and antiestrogen resistance in breast
      cancer cells, we studied the effect of WT1 on tamoxifen responsiveness in ERalpha
      positive MCF-7 cells. We found that overexpression of WT1 in MCF-7 markedly
      abrogated tamoxifen-induced cell apoptosis and 17beta-estradiol (E(2))-mediated
      cell proliferation. The expressions of ERalpha and its downstream target genes
      were significantly repressed following overexpression of WT1, whereas the down
      regulation of WT1 by WT1 shRNA could enhance ERalpha expression and the
      sensitivity to tamoxifen treatment in ERalpha-negative MDA468 and HCC1954 cells
      that express high levels of WT1. Furthermore, we have confirmed that the WT1
      protein can bind to endogenous WT1 consensus sites in the proximal promoter of
      ERalpha and thus inhibit the transcriptional activity of the ERalpha promoter in
      a WT1 site sequence-specific manner. Our study clearly implicates WT1 as a
      mediator of antiestrogen resistance in breast cancer through down-regulation of
      ERalpha expression and supports the development of WT1 inhibitors as a potential
      means of restoring antiestrogen responsiveness in breast cancer therapy.

PMID- 18708367
TI  - Bortezomib-resistant nuclear factor-kappaB activity in multiple myeloma cells.
AB  - Bortezomib (Velcade/PS341), a proteasome inhibitor used in the treatment of
      multiple myeloma (MM), can inhibit activation of nuclear factor-kappaB (NF
      kappaB), a family of transcription factors often deregulated and constitutively
      activated in primary MM cells. NF-kappaB can be activated via several distinct
      mechanisms, including the proteasome inhibitor-resistant (PIR) pathway. It
      remains unknown what fraction of primary MM cells harbor constitutive NF-kappaB
      activity maintained by proteasome-dependent mechanisms. Here, we report an
      unexpected finding that constitutive NF-kappaB activity in 10 of 14 primary MM
      samples analyzed is refractory to inhibition by bortezomib. Moreover, when MM
      cells were cocultured with MM patient-derived bone marrow stromal cells (BMSC),
      microenvironment components critical for MM growth and survival, further
      increases in NF-kappaB activity were observed that were also refractory to
      bortezomib. Similarly, MM-BMSCs caused PIR NF-kappaB activation in the RPMI8226
      MM cell line, leading to increased NF-kappaB-dependent transcription and
      resistance to bortezomib-induced apoptosis. Our findings show that primary MM
      cells frequently harbor PIR NF-kappaB activity that is further enhanced by the
      presence of patient-derived BMSCs. They also suggest that this activity is likely
      relevant to the drug resistance development in some patients. Further elucidation
      of the mechanism of PIR NF-kappaB regulation could lead to the identification of
      novel diagnostic biomarkers and/or therapeutic targets for MM treatment.

PMID- 18708368
TI  - The multifunctional protein glyceraldehyde-3-phosphate dehydrogenase is both
      regulated and controls colony-stimulating factor-1 messenger RNA stability in
      ovarian cancer.
AB  - Although glyceraldehyde-3-phosphate dehydrogenase's (GAPDH) predilection for AU
      rich elements has long been known, the expected connection between GAPDH and
      control of mRNA stability has never been made. Recently, we described GAPDH
      binding the AU-rich terminal 144 nt of the colony-stimulating factor-1 (CSF-1) 3'
      untranslated region (UTR), which we showed to be an mRNA decay element in ovarian
      cancer cells. CSF-1 is strongly correlated with the poor prognosis of patients
      with ovarian cancer. We investigated the functional significance of GAPDH's
      association with CSF-1 mRNA and found that GAPDH small interfering RNA reduces
      both CSF-1 mRNA and protein levels by destabilizing CSF-1 mRNA. CSF-1 mRNA half
      lives were decreased by 50% in the presence of GAPDH small interfering RNA. RNA
      footprinting analysis of the 144 nt CSF-1 sequence revealed that GAPDH associates
      with a large AU-rich-containing region. The effects of binding of GAPDH protein
      or ovarian extracts to mutations of the AU-rich regions within the footprint were
      consistent with this finding. In a tissue array containing 256 ovarian and
      fallopian tube cancer specimens, we found that GAPDH was regulated in these
      cancers, with almost 50% of specimens having no GAPDH staining. Furthermore, we
      found that low GAPDH staining was associated with a low CSF-1 score (P = 0.008).
      In summary, GAPDH, a multifunctional protein, now adds regulation of mRNA
      stability to its repertoire. We are the first to evaluate the clinical role of
      GAPDH protein in cancer. In ovarian cancers, we show that GAPDH expression is
      regulated, and we now recognize that one of the many functions of GAPDH is to
      promote mRNA stability of CSF-1, an important cytokine in tumor progression.

PMID- 18708370
TI  - Mechanisms and consequences of chromosomal translocation.
AB  - A 2006 National Cancer Institute workshop on chromosomal translocations brought
      together laboratory, clinical, and population scientists to cross-fertilize and
      catalyze research on this important disease process. The deliberations revealed
      significant contrasts between two types of translocations that result in either
      deregulated expression of oncogenes or formation of novel fusion genes. The
      classic oncogene-activating translocation, MYC-IGH, has been elucidated in terms
      of molecular structure and functional consequences yet has little epidemiologic
      characterization. In comparison, the archetypal fusion-gene translocation, BCR
      ABL, has well-described clinical manifestations but is less defined with regard
      to mechanism of generation. Interdisciplinary collaboration on chromosomal
      translocations should yield additional insights regarding their biological
      significance and potential as targets for intervention.

PMID- 18708369
TI  - The role of the BRCA2 gene in susceptibility to prostate cancer revisited.
AB  - Prostate cancer is a genetically complex disease with multiple predisposing
      factors affecting presentation, progression, and outcome. Epidemiologic studies
      have long shown an aggregation of breast and prostate cancer in some families.
      More recently, studies have reported an apparent excess of prostate cancer cases
      among BRCA2 mutation-carrying families. Additionally, population-based screens of
      early-onset prostate cancer patients have suggested that the prevalence of
      deleterious BRCA2 mutations in this group is 1% to 2%, imparting a significantly
      increased risk of the disease compared with noncarrier cases. However, studies of
      high-risk prostate cancer families suggest that BRCA2 plays at most a minimal
      role in these individuals, highlighting the potential genetic heterogeneity of
      the disease. In this commentary, we review the current literature and hypotheses
      surrounding the relationship between BRCA2 mutations and susceptibility to
      prostate cancer and speculate on the potential for involvement of additional
      genes.

PMID- 18708371
TI  - Cyclooxygenase-2 inhibitors in colorectal cancer prevention: point.
AB  - The limited success of current treatments for most advanced common malignancies
      highlights the importance of cancer prevention. Clinical trials on cyclooxygenase
      (COX) inhibitor drugs showed the potential of chemoprevention as a strategy for
      reducing cancer incidence, although not without associated side effects. The
      attractiveness of these drugs partly stems from an ability to engage multiple
      mechanisms of action by their potential to influence multiple components of the
      carcinogenesis pathway, from initiation to progression. There are two isoforms of
      the COX enzymes. COX-1 is constitutively expressed in normal tissues and serves
      as a "housekeeper" of mucosal integrity, whereas COX-2 is an immediate early
      response gene that is highly inducible by neoplastic and inflammatory stimuli.
      COX-2 is significantly overexpressed in colorectal neoplasms, making it an
      attractive therapeutic target. The drug market has been revolutionized by the
      development of preparations targeted selectively against COX-2, and a proof of
      concept has been achieved. Chemoprevention of colorectal cancer is already
      possible with celecoxib, but it is still not the ultimate drug of choice
      especially because of the cardiovascular risk associated with COX-2 inhibitors.
      Better patient selection and more effective and safer drugs are needed. Celecoxib
      is probably best used in a subset of individuals at moderate to high colorectal
      cancer risk and low risk of cardiovascular disease.

PMID- 18708372
TI  - Cyclooxygenase-2 inhibitors in colorectal cancer prevention: counterpoint.
AB  - Aspirin is the best chemoprevention agent for colorectal cancer risk reduction
      despite the fact that the evidence for a decrease in mortality is weak. The
      cyclooxygenase-2 selective agents (COXIBS) have an efficacy similar to that of
      aspirin for most gastrointestinal (GI) lesions but not esophagus. Specifically,
      there are beneficial short term effects of COXIBs on the risk of colorectal
      adenoma as shown in the Approve, PreSAP, and APC studies. However, there is still
      an increased risk of upper GI complications with COXIBs when compared with
      placebo, and this risk may increase further in some people when aspirin is also
      consumed. Whereas aspirin reduces the risk of cardiovascular events, COXIBs and
      most traditional nonsteroidal anti-inflammatory drugs (but not all) are both
      associated with an increased risk of thrombotic cardiovascular events compared
      with placebo. In conclusion, COXIBs have a niche role for patients with familial
      adenomatous polyposis. The value of aspirin remains with respect for efficacy,
      mainly in the esophagus, and the side effect profile, especially in the elderly
      if given with acid suppression therapy. COXIBs should be used in younger
      populations, but if they are considered in the elderly because of increased GI
      risks, and the cardiovascular risk is also increased, then combination treatment
      with aspirin and a proton-pump inhibitor should also be considered instead, such
      as in the ASPECT trial.

PMID- 18708373
TI  - Social-cognitive and school factors in lifetime smoking among adolescents.
AB  - BACKGROUND: Smoking is a serious health threat and identifying risk factors for
      smoking is thus of great importance. The aim of the study was to examine the
      effects of social-cognitive factors and school factors on lifetime smoking status
      among adolescents. METHODS: The study was based on cross-sectional data on 2,913
      Danish adolescents in grade 7 attending 118 randomly selected public schools.
      Social-cognitive factors were examined with five measures: self-efficacy to
      resist pressure to smoke, social influence (norms), social influence (behavior),
      social influence (pressure), and attitude. We used multilevel analyses to
      estimate the associations between social-cognitive factors and lifetime smoking
      status as well as the group-level effects of school, school class, and gender
      group in the school class. RESULTS: Each social-cognitive factor was
      significantly associated with lifetime smoking status, even when several
      potential confounders and the effects of school, school class, and gender group
      were taken into account. Of the three group-level school factors, gender group in
      the school class had the strongest effect on smoking status. CONCLUSION: We
      conclude that self-efficacy to resist pressure to smoke, attitude, and the three
      types of social influence are significantly associated with lifetime smoking
      status, even when the effects of group-level school factors are taken into
      account. The strong effect of gender group in school class on lifetime smoking
      status indicates that prevention actions should address the social context of
      adolescents.

PMID- 18708374
TI  - Psychologic predictors of cancer information avoidance among older adults: the
      role of cancer fear and fatalism.
AB  - Little is known about the correlates of cancer information avoidance and whether
      people with negative feelings and beliefs about cancer are more likely to avoid
      cancer information, allowing such thoughts and feelings to persist unchallenged.
      Using the Extended Parallel Processing Model as a theoretical guide, we tested
      the hypothesis that cancer fear and fatalism would predict cancer information
      avoidance but that part of this effect would be mediated via cancer-specific
      threat and efficacy beliefs. A community sample of older adults, ages 50 to 70
      years (n = 1,442), completed a postal questionnaire that included the Powe
      Fatalism Inventory and the Champion Cancer Fear scale along with other measures
      of cancer-specific beliefs and demographic variables. Higher levels of cancer
      fear were positively associated with higher levels of cancer information
      avoidance, and part of this relationship was mediated via perceived cancer
      severity. The relationship between cancer fatalism and cancer information
      avoidance was partly mediated by severity and response-efficacy beliefs. This
      research shows that people with negative views about cancer are more likely to
      avoid cancer information. This means people with higher levels of cancer fear and
      fatalism are less likely to learn about positive developments made in the field
      of cancer control, allowing such negative feelings and views to continue.
      Research needs to focus on how to get positive messages about improvements in
      cancer prevention and control through to people who are fearful of and fatalistic
      about the disease.

PMID- 18708375
TI  - Reproducibility of serum pituitary hormones in women.
AB  - Endogenous pituitary hormones are commonly used in clinical and epidemiologic
      studies and some of them are thought to influence the risk of several diseases in
      women. In most studies, endogenous levels of pituitary hormones are usually
      assessed at a single point in time, assuming that this single measurement
      represents the long-term biomarker status of the individual. Such an assumption
      is rarely tested and may not always be valid. This study examined the
      reproducibility of the following pituitary hormones: adrenocorticotropic hormone
      (ACTH), growth hormone, follicle-stimulating hormone (FSH), luteinizing hormone
      (LH), thyroid-stimulating hormone (TSH), and prolactin, measured using the
      Luminex xMap method in sera of healthy premenopausal and postmenopausal women.
      The study included 30 premenopausal women with three yearly samples and 35
      postmenopausal women with two repeated yearly samples randomly selected from an
      existing prospective cohort. Analysis of intraclass correlation coefficients
      suggested higher reproducibility in postmenopausal women compared with
      premenopausal women for the following hormones: FSH (0.72 and 0.37,
      respectively), LH (0.83 and 0.44, respectively), and growth hormone (0.60 and
      0.35, respectively). The intraclass correlation coefficients were relatively high
      and similar between postmenopausal and premenopausal women for ACTH (0.95 and
      0.94, respectively), TSH (0.85 and 0.85, respectively), and prolactin (0.72 and
      0.69, respectively). This study found that serum concentrations of FSH, LH, and
      growth hormone are stable in postmenopausal women and that ACTH, TSH, and
      prolactin are stable in both premenopausal and postmenopausal women, suggesting
      that a single measurement may reliably categorize average levels over at least a
      2-year period.

PMID- 18708377
TI  - Measurement of sex steroid hormones in breast adipocytes: methods and
      implications.
AB  - BACKGROUND: The lack of validated methods for measuring sex steroid hormones in
      breast tissue has limited our knowledge of their role in the development of
      breast cancer. We explored the feasibility of measuring hormones in breast
      adipocytes for epidemiologic and clinical studies by refining an existing assay
      procedure and assessing the reliability of hormone measurements using the
      modified assay. This report presents the reproducibility of measurements of
      androstenedione (A), testosterone (T), estrone (E(1)), and estradiol (E(2)),
      using breast adipose tissue samples obtained from women undergoing surgical
      resection for a variety of pathologic conditions. METHODS: Breast adipose tissues
      were obtained from 20 women. Measurements of the steroid hormones were carried
      out by harvesting oil from adipocytes following enzymatic digestion of the
      adipose tissue, extracting and chromatographing the steroids, and quantifying
      them by RIA. The study was conducted in three phases: first, samples from five
      women were used to assess the assay procedure; following this, tissues from an
      additional five women were assayed repeatedly to determine reproducibility of the
      hormone measurements. Finally, using samples from 10 women undergoing surgical
      resection of a breast tumor, we evaluated hormone concentrations in samples
      distal and proximal to the tumor. The assay coefficient of variation and
      intraclass correlation coefficient were used to assess hormone reproducibility.
      RESULTS: The within-batch coefficients of variation ranged from 5% to 17%, and
      between-batch estimates were between 2% and 10%, suggesting that E(1), E(2), A,
      and T can be reliably measured in breast adipocytes. Among samples obtained from
      women undergoing surgical resection of a breast tumor, hormone levels did not
      differ between adipose tissue fragments that were distal or proximal to the
      tumor, with the possible exception of E(1) in which levels were 10% higher in
      distal fragments. CONCLUSION: These data support the feasibility of measuring
      steroid hormone concentrations in breast adipocytes in epidemiologic studies.
      Future investigations that include the measurement of hormones in the breast
      microenvironment may have value in understanding breast carcinogenesis,
      developing prevention strategies, and assessing hormonal treatments.

PMID- 18708376
TI  - ESR1 promoter hypermethylation does not predict atypia in RPFNA nor persistent
      atypia after 12 months tamoxifen chemoprevention.
AB  - PURPOSE: Currently, we lack biomarkers to predict whether high-risk women with
      mammary atypia will respond to tamoxifen chemoprevention. EXPERIMENTAL DESIGN:
      Thirty-four women with cytologic mammary atypia from the Duke University High
      Risk clinic were offered tamoxifen chemoprevention. We tested whether ESR1
      promoter hypermethylation and/or estrogen receptor (ER) protein expression by
      immunohistochemistry predicted persistent atypia in 18 women who were treated
      with tamoxifen for 12 months and in 16 untreated controls. RESULTS: We observed a
      statistically significant decrease in the Masood score of women on tamoxifen
      chemoprevention for 12 months compared with control women. This was a significant
      interaction effect of time (0, 6, and 12 months) and treatment group (tamoxifen
      versus control) P = 0.0007. However, neither ESR1 promoter hypermethylation nor
      low ER expression predicted persistent atypia in Random Periareolar Fine Needle
      Aspiration after 12 months tamoxifen prevention. CONCLUSIONS: Results from this
      single institution pilot study provide evidence that, unlike for invasive breast
      cancer, ESR1 promoter hypermethylation and/or low ER expression is not a reliable
      marker of tamoxifen-resistant atypia.

PMID- 18708378
TI  - Hemoglobin adducts of benzene oxide in neonatal and adult dried blood spots.
AB  - Adducts of reactive chemicals with hemoglobin (Hb) or human serum albumin can be
      used as biomarkers of internal doses of carcinogens. Because dried blood spots
      are easier to collect and store than conventional venous blood samples, they
      encourage applications of biomarkers of exposure in large epidemiologic studies.
      In addition, neonatal dried blood spot can be used to investigate chemical
      exposures in utero. Here, we report a simple method to isolate Hb from dried
      blood spot with high recovery and purity using the addition of ethanol to aqueous
      dried blood spot extracts. To prove the concept that dried blood spot-derived
      proteins can be used to assay for adducts, we measured Hb adducts of benzene
      oxide, a reactive metabolite of the ubiquitous air pollutant benzene in nine
      neonatal and nine adult dried blood spots (from volunteer subjects), using a gas
      chromatography-mass spectrometry method that we had previously developed. For
      comparison, benzene oxide-Hb adducts were measured in the same nine adult
      subjects using Hb that had been isolated and purified using our conventional
      method for venous blood. The geometric mean of benzene oxide-Hb levels in all
      dried blood spot samples ranged from 27.7 to 33.1 pmol/g globin. Neither of the
      comparisons of mean (logged) benzene oxide-Hb levels between sources (adult
      conventional versus adult dried blood spot and adult dried blood spot versus
      newborn dried blood spot) showed a significant difference. Based upon the
      estimated variance of the benzene oxide-Hb levels, we had 80% power to detect a
      1.7-fold difference in geometric mean levels of benzene oxide-Hb in our sample of
      nine subjects.

PMID- 18708379
TI  - Multiplex genotyping as a biomarker for susceptibility to carcinogenic exposure
      in the FLEHS biomonitoring study.
AB  - Cancer has been suggested to result from interactions between genetic and
      environmental factors, and certain subgroups in the general population may be at
      increased risk because of their relatively higher susceptibility to environmental
      carcinogens. The current study, part of a large biomonitoring study conducted in
      Flanders from 2002 to 2006 (The Flanders Environment and Health Survey), aims to
      determine these susceptible subpopulations based on multiple genotypic
      differences between individuals. A random selection of 429 adolescents and 361
      adults was genotyped for 36 polymorphisms in 23 genes selected because of their
      known role in carcinogen metabolism, DNA repair, and oxidative stress. In both
      age groups, relationships between endogenous exposure to organochloride
      substances (polychlorinated biphenyl, hexachlorobenzene, dichlorodiphenyl
      dichloroethane), metals (cadmium, lead), and urinary metabolites (1
      hydroxypyrene, trans-trans muconic acid) versus genotoxic effects (Comet assay
      and micronuclei in lymphocytes, and urinary 8-hydroxydeoxyguanosine) were
      investigated. In addition, in the study among adults, the relationship of these
      exposures with several tumor markers (prostate-specific antigen, carcinoembryonic
      antigen, and p53) was tested. The impact of the genotype on established exposure
      effect relationships was evaluated. Eight exposure-effect relationships were
      found, including three novel associations, with an impact of various genotypes,
      predominantly affecting biotransformation and oxidative stress response. This
      study shows that at least part of the interindividual differences in
      relationships between carcinogen exposure and genotoxic effect can be explained
      by genotypic differences, enabling the identification of more susceptible
      subgroups for environmental cancer risks. This may be of relevance for
      environmental health policy setting.

PMID- 18708380
TI  - No acute and persistent DNA damage after an Ironman triathlon.
AB  - During acute and strenuous exercise, the enhanced formation of reactive oxygen
      species can induce damage to lipids, proteins, and nucleic acids. The aim of this
      study was to investigate the effect of an Ironman triathlon (3.8 km swim, 180 km
      cycle, 42 km run), as a prototype of ultra-endurance exercise, on DNA stability.
      As biomarkers of genomic instability, the number of micronuclei, nucleoplasmic
      bridges, and nuclear buds were measured within the cytokinesis-block micronucleus
      cytome assay in once-divided peripheral lymphocytes of 20 male triathletes. Blood
      samples were taken 2 days before, within 20 min after the race, and 5 and 19 days
      post-race. Overall, the number of micronuclei decreased (P < 0.05) after the
      race, remained at a low level until 5 days post-race, and declined further to 19
      days post-race (P < 0.01). The frequency of nucleoplasmic bridges and nuclear
      buds did not change immediately after the triathlon. The number of nucleoplasmic
      bridge declined from 2 days pre-race to 19 days post-exercise (P < 0.05). The
      frequency of nuclear buds increased after the triathlon, peaking 5 days post-race
      (P < 0.01) and decreased to basic levels 19 days after the race (P < 0.01). The
      results suggest that an Ironman triathlon does not cause long-lasting DNA damage
      in well-trained athletes.

PMID- 18708381
TI  - Effect of nonmotorized wheel running on mammary carcinogenesis: circulating
      biomarkers, cellular processes, and molecular mechanisms in rats.
AB  - The objective of this experiment was to identify circulating growth factors,
      hormones, and cellular and molecular mechanisms that account for the effects of
      physical activity on mammary carcinogenesis. A total of 120 female Sprague-Dawley
      rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter
      were randomized to either a physically active or a sedentary control group.
      Individually housed rats were given free access to a nonmotorized, computer
      controlled activity wheel and running behavior was reinforced by food reward.
      Rats self-determined their daily intensity and duration of running. Sedentary
      control rats received the same amount of food as the physically active rats to
      which they were paired. Physical activity reduced mammary cancer incidence (P =
      0.015) and cancer multiplicity (P = 0.01). Physical activity induced changes in
      plasma insulin, insulin-like growth factor-I, and corticosterone, suggesting that
      mechanisms regulating glucose homeostasis were affected. Western blot analyses of
      mammary carcinomas revealed that proteins involved in cell proliferation were
      reduced (P < 0.001) and those involved in apoptosis via the mitochondrial pathway
      were elevated (P < 0.001) by physical activity. The hypothesis that these effects
      were mediated by activation of AMP-activated protein kinase, and down-regulation
      of protein kinase B, which collectively down-regulate the activity of the
      mammalian target of rapamycin, was evaluated. Evidence in support of this
      hypothesis was found in the Western blot analyses of mammary carcinomas, mammary
      gland, liver, and skeletal muscle. Collectively, these findings provide a
      rationale for additional studies of energy-sensing pathways in the elucidation of
      mechanisms that account for the inhibition of carcinogenesis by physical
      activity.

PMID- 18708382
TI  - Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and
      conjugate metabolites in healthy human subjects.
AB  - BACKGROUND: Ginger shows promising anticancer properties. No research has
      examined the pharmacokinetics of the ginger constituents 6-gingerol, 8-gingerol,
      10-gingerol, and 6-shogaol in humans. We conducted a clinical trial with 6
      gingerol, 8-gingerol, 10-gingerol, and 6-shogaol, examining the pharmacokinetics
      and tolerability of these analytes and their conjugate metabolites. METHODS:
      Human volunteers were given ginger at doses from 100 mg to 2.0 g (N = 27), and
      blood samples were obtained at 15 minutes to 72 hours after a single p.o. dose.
      The participants were allocated in a dose-escalation manner starting with 100 mg.
      There was a total of three participants at each dose except for 1.0 g (N = 6) and
      2.0 g (N = 9). RESULTS: No participant had detectable free 6-gingerol, 8
      gingerol, 10-gingerol, or 6-shogaol, but 6-gingerol, 8-gingerol, 10-gingerol, and
      6-shogaol glucuronides were detected. The 6-gingerol sulfate conjugate was
      detected above the 1.0-g dose, but there were no detectable 10-gingerol or 6
      shogaol sulfates except for one participant with detectable 8-gingerol sulfate.
      The C(max) and area under the curve values (mean +/- SE) estimated for the 2.0-g
      dose are 0.85 +/- 0.43, 0.23 +/- 0.16, 0.53 +/- 0.40, and 0.15 +/- 0.12
      microg/mL; and 65.6.33 +/- 44.4, 18.1 +/- 20.3, 50.1 +/- 49.3, and 10.9 +/- 13.0
      microg x hr/mL for 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol. The
      corresponding t(max) values are 65.6 +/- 44.4, 73.1 +/- 29.4, 75.0 +/- 27.8, and
      65.6 +/- 22.6 minutes, and the analytes had elimination half-lives <2 hours. The
      8-gingerol, 10-gingerol, and 6-shogaol conjugates were present as either
      glucuronide or sulfate conjugates, not as mixed conjugates, although 6-gingerol
      and 10-gingerol were an exception. CONCLUSION: Six-gingerol, 8-gingerol, 10
      gingerol, and 6-shogaol are absorbed after p.o. dosing and can be detected as
      glucuronide and sulfate conjugates.

PMID- 18708383
TI  - Cancer screening for underserved women: the Breast and Cervical Cancer
      Intervention Study.
AB  - OBJECTIVE: To report on the effect of the Breast and Cervical Cancer Intervention
      Study (BACCIS), a multicomponent intervention conducted in the San Francisco Bay
      Area between 1992 and 1997. METHODS: BACCIS targeted approximately 25,000
      multiethnic, underserved women in eight neighborhoods and the public health
      clinics that served them. An outreach intervention using lay health worker peers
      and clinic provider inreach intervention to improve breast and cervical cancer
      screening were evaluated in a quasi-experimental, controlled trial with pretest
      and posttest household surveys of 1,599 and 1,616 women, respectively. Surveys
      were conducted in English, Spanish, Mandarin, and Cantonese. RESULTS: Analyses of
      community survey results showed no significant improvement in reported screening
      behaviors. Reports of mammography in the intervention areas in the previous 2
      years, or for Pap smear in the previous 3 years, did not differ significantly (73
      71% and 84-87%, respectively, for pretest and posttest surveys). CONCLUSION: High
      baseline screening rates, lack of sensitive measures of change at the population
      level, contamination of the control group, and an imbalance of predictive factors
      at baseline contributed to the difficulty of assessing the value of the
      intervention. Lessons learned from this inconclusive study may be of value to
      future community intervention studies of cancer screening and other health
      behaviors in multiethnic underserved urban populations.

PMID- 18708384
TI  - Effects of socioeconomic status and treatment disparities in colorectal cancer
      survival.
AB  - BACKGROUND: Poor survival among colorectal cancer (CRC) cases has been associated
      with African-American race and low socioeconomic status (SES). However, it is not
      known whether the observed poor survival of African-American CRC cases is due to
      SES itself and/or treatment disparities. We set out to determine this using data
      from the large, population-based California Cancer Registry database. METHODS: A
      case-only analysis of CRC was conducted including all age groups using California
      Cancer Registry data from 1994 to 2003, including descriptive analysis of
      relevant clinical variables, race, and SES. CRC-specific survival univariate
      analyses were conducted using the Kaplan-Meier method. Multivariate survival
      analyses were done using Cox proportional hazards ratios (HR). RESULTS: Incident
      cases of colon (90,273) and rectal (37,532) cancer were analyzed, including
      91,739 (71.8%) non-Hispanic Whites, 8,535 (6.7%) African-Americans, 14,943
      (11.7%) Hispanics, 3,564 (2.8%) Chinese, and 7,950 (6.2%) non-Chinese Asians.
      African-Americans had a greater proportion of metastatic stage at presentation (P
      < 0.0001) and decreased CRC-specific survival (P < 0.0001 for colon and rectal
      cancer). After adjustment for age, sex, histology, site within the colon, and
      stage, African-Americans [colon: HR, 1.19; 95% confidence interval (95% CI), 1.14
      1.25; rectum: HR, 1.27; 95% CI, 1.17-1.38] had an increased risk of death
      compared with Caucasians. However, after further adjustment for SES and
      treatment, the risk of death for African-Americans compared with Caucasians was
      substantially diminished (colon: HR, 1.08; 95% CI, 1.03-1.13; rectum: HR, 1.11;
      95% CI, 1.02-1.20). CONCLUSION: Among CRC cases, disparities in treatment and SES
      largely explain the observed decreased survival of African-Americans,
      underscoring the importance of health disparity research in this disease.

PMID- 18708385
TI  - Disparities in the receipt of fecal occult blood test versus endoscopy among
      Filipino American immigrants.
AB  - BACKGROUND: This report examines disparities associated with the type of
      colorectal screening test, fecal occult blood test versus endoscopy, within a
      particular racial/ethnic group, Filipino American immigrants. METHODS: Between
      July 2005 and October 2006, Filipino Americans aged 50 to 75 years from 31
      community organizations in Los Angeles completed a 15-minute survey in English
      (65%) or Filipino (35%). RESULTS: Of the 487 respondents included in this
      analysis, 257 (53%) had never received any type of colorectal cancer screening.
      Among the 230 subjects who had ever received a routine screening test, 78 had
      fecal occult blood test only (16% of the total sample), and 152 had endoscopy
      with or without fecal occult blood test (31% of the total sample). After
      controlling for access to care and key demographic variables in a multivariate
      analysis, only two characteristics distinguished between respondents who had
      fecal occult blood test only versus those who had endoscopy: acculturation,
      assessed by percent lifetime in the United States and language of interview, and
      income. CONCLUSIONS: Our data suggest a two-tier system, fecal occult blood test
      for less acculturated Filipino Americans with lower income versus endoscopy for
      Filipino immigrants with higher levels of acculturation and income. The disparity
      persists after adjusting for access to care. Instead of treating minority groups
      as monolithic, differences within groups need to be examined so that
      interventions can be appropriately targeted.

PMID- 18708386
TI  - Disparities in cervical cancer screening between Asian American and Non-Hispanic
      white women.
AB  - BACKGROUND: Asian American women have higher cervical cancer mortality rates than
      non-Hispanic White women, yet have lower Pap screening rates than their White
      counterparts. This study examined whether ethnic differences in the use of Pap
      screening were associated with differences in cultural views, controlling for
      demographic and access factors. METHODS: Cross-sectional survey data from the
      Commonwealth 2001 Health Care Quality Survey were used. Non-Hispanic White (n =
      2,146) and Asian American women (including Chinese, Vietnamese, Korean, Filipino,
      and Japanese; n = 259) were included in this study. Eastern cultural views were
      measured by beliefs in the role of self-care and luck. Access factors (having
      health insurance, regular providers, and communication with providers) and
      demographics of patients and providers were measured. The outcome was receipt of
      a Pap test in the past 2 years. RESULTS: Asian American women had a lower rate of
      obtaining a recent Pap test (70%) than non-Hispanic White women (81%; P = 0.001).
      More Asians believed in the role of luck and self-care and experienced access
      barriers than Whites (P < 0.0001). Women with less Eastern cultural views are
      more likely to be recently screened than women with more (odds ratio, 1.08; 95%
      confidence interval, 1.00-1.16; P < 0.05). All access factors and provider gender
      types predicted the outcome. Within the Asian subgroups, Vietnamese women had
      lower screening rates (55%) and greater Eastern cultural views than their Asian
      counterparts. CONCLUSION: More research is needed to understand cultural and
      other barriers to Pap screening in high-risk Asian women, and attention should be
      paid to within-group differences.

PMID- 18708388
TI  - Increased childhood liver cancer mortality and arsenic in drinking water in
      northern Chile.
AB  - Arsenic in drinking water is an established cause of lung, bladder, and skin
      cancers in adults and may also cause adult kidney and liver cancers. Some
      evidence for these effects originated from region II of Chile, which had a period
      of elevated arsenic levels in drinking water, in particular from 1958 to 1970.
      This unique exposure scenario provides a rare opportunity to investigate the
      effects of early-life arsenic exposure on childhood mortality; to our knowledge,
      this is the first study of childhood cancer mortality and high concentrations of
      arsenic in drinking water. In this article, we compare cancer mortality rates
      under the age of 20 in region II during 1950 to 2000 with those of unexposed
      region V, dividing subjects into those born before, during, or after the peak
      exposure period. Mortality from the most common childhood cancers, leukemia and
      brain cancer, was not increased in the exposed population. However, we found that
      childhood liver cancer mortality occurred at higher rates than expected. For
      those exposed as young children, liver cancer mortality between ages 0 and 19 was
      especially high: the relative risk (RR) for males born during this period was 8.9
      [95% confidence interval (95% CI), 1.7-45.8; P = 0.009]; for females, the
      corresponding RR was 14.1 (95% CI, 1.6-126; P = 0.018); and for males and females
      pooled, the RR was 10.6 (95% CI, 2.9-39.2; P < 0.001). These findings suggest
      that exposure to arsenic in drinking water during early childhood may result in
      an increase in childhood liver cancer mortality.

PMID- 18708387
TI  - Involuntary smoking and head and neck cancer risk: pooled analysis in the
      International Head and Neck Cancer Epidemiology Consortium.
AB  - Although active tobacco smoking has been identified as a major risk factor for
      head and neck cancer, involuntary smoking has not been adequately evaluated
      because of the relatively low statistical power in previous studies. We took
      advantage of data pooled in the International Head and Neck Cancer Epidemiology
      Consortium to evaluate the role of involuntary smoking in head and neck
      carcinogenesis. Involuntary smoking exposure data were pooled across six case
      control studies in Central Europe, Latin America, and the United States. Adjusted
      odds ratios (OR) and 95% confidence interval (95% CI) were estimated for 542
      cases and 2,197 controls who reported never using tobacco, and the heterogeneity
      among the study-specific ORs was assessed. In addition, stratified analyses were
      done by subsite. No effect of ever involuntary smoking exposure either at home or
      at work was observed for head and neck cancer overall. However, long duration of
      involuntary smoking exposure at home and at work was associated with an increased
      risk (OR for >15 years at home, 1.60; 95% CI, 1.12-2.28; P(trend) < 0.01; OR for
      >15 years at work, 1.55; 95% CI, 1.04-2.30; P(trend) = 0.13). The effect of
      duration of involuntary smoking exposure at home was stronger for pharyngeal and
      laryngeal cancers than for other subsites. An association between involuntary
      smoking exposure and the risk of head and neck cancer, particularly pharyngeal
      and laryngeal cancers, was observed for long duration of exposure. These results
      are consistent with those for active smoking and suggest that elimination of
      involuntary smoking exposure might reduce head and neck cancer risk among never
      smokers.

PMID- 18708389
TI  - Salt and gastric adenocarcinoma: a population-based cohort study in Norway.
AB  - BACKGROUND: Gastric adenocarcinoma is the second leading cause of cancer death
      worldwide. It has been suggested that consumption of salted foods is associated
      with increased risk of this cancer, but the results of the few available
      prospective studies are contradictory. METHODS: A population-based, prospective
      cohort study in Nord-Trondelag County in Norway during 1984 to 2002 addressed
      dietary salt intake in relation to risk of gastric adenocarcinoma. In 1984 to
      1986, all adult county residents were invited to a health survey in which
      participants answered questionnaires concerning dietary salt intake and other
      factors. Gastric adenocarcinomas were identified in the Norwegian Cancer
      Registry. Relative risks were calculated using Cox proportional hazards
      regression models, adjusted for potentially confounding factors. RESULTS: Follow
      up of 1,122,765 person-years at risk among 73,133 cohort members disclosed 313
      incident cases of gastric adenocarcinomas occurring at least 3 years after
      inclusion into the cohort. There were no statistically significant associations
      between different levels of salt intake and risk of gastric adenocarcinoma. High
      consumers of dietary salt were not at increased risk of developing gastric
      adenocarcinoma compared with low consumers (hazard ratio, 1.0; 95% confidence
      interval, 0.7-1.4), and no dose-response effect was observed (P(trend) = 0.55).
      CONCLUSION: High intake of dietary salt does not appear to increase the risk of
      gastric adenocarcinoma in this low-incidence western population.

PMID- 18708390
TI  - Prevalence of genital human papilloma virus infection and genotypes among young
      women in Sicily, South Italy.
AB  - Infection with oncogenic human papilloma virus (HPV) types is a necessary cause
      of cervical cancer. This study assessed the prevalence of HPV infection and
      genotypes among 1,006 randomly selected women, ages 18 to 24 years, living in
      Sicily (south Italy). The overall HPV rate was 24.1% (95% confidence interval,
      21.5-26.9). The most frequent types were HPV-16 (4.5%), HPV-53 (2.7%), and HPV-84
      (2.6%). The prevalence of vaccine types HPV-6, HPV-11, and HPV-18 was 1.4%, 0.1%,
      and 1.3%, respectively. Cytologic abnormalities were uncommon (3.1%) and
      associated with HPV detection (P < 0.0001). The only risk factor for HPV
      infection was the number of sexual partners (women with 2-3 partners versus women
      with 1 partner: odds ratio, 3.86; 95% confidence interval, 2.45-6.09). Genital
      HPV infection is relatively high in young Italian women. The high prevalence of
      viral types other than vaccine types should be taken into account to ensure
      accurate postvaccine surveillance and early detection of a possible genotype
      replacement.

PMID- 18708391
TI  - Breast cancer risk polymorphisms and interaction with ionizing radiation among
      U.S. radiologic technologists.
AB  - Genome-wide association studies are discovering relationships between single
      nucleotide polymorphisms and breast cancer, but the functions of these single
      nucleotide polymorphisms are unknown and environmental exposures are likely to be
      important. We assessed whether breast cancer risk single-nucleotide polymorphisms
      interacted with ionizing radiation, a known breast carcinogen, among 859 cases
      and 1,083 controls nested in the U.S. Radiologic Technologists cohort. Among 11
      Breast Cancer Association Consortium risk single-nucleotide polymorphisms, we
      found that the genotype-associated breast cancer risk varied significantly by
      radiation dose for rs2107425 in the H19 gene (P(interaction) = 0.001). H19 is a
      maternally expressed imprinted mRNA that is closely involved in regulating the
      IGF2 gene and could exert its influence by this or by some other radiation
      related pathway.

PMID- 18708393
TI  - Studying genetic research participants: lessons from the "Learning About Research
      in North Carolina" study.
AB  - Given the prohibitive cost of recruiting large and diverse populations for
      genetic explorations in cancer research, there has been a call for genetic
      studies to engage existing cohorts of research participants. This strategy could
      lead to more efficient recruitment and potentially result in significant advances
      in the understanding of cancer etiology and treatment. The Learning About
      Research in North Carolina (LeARN) study responded to the National Human Genome
      Research Institute interest in research on how study participants from diverse
      populations who had participated in genetic research perceived the risks and
      benefits of participating in combined epidemiologic-genetic research, how well
      they understand the purpose of the research and the uses to which the research
      results may be put, and how involvement in such research affects perceptions of
      disease causality. In this article, we give an overview of the LeARN study,
      summarizing the methods we used, challenges we encountered, and lessons learned
      about recruiting participants who have previously participated in genetic
      research.

PMID- 18708392
TI  - Serum organochlorine pesticide residues and risk of testicular germ cell
      carcinoma: a population-based case-control study.
AB  - Testicular germ cell carcinoma (TGCC) is the most common malignancy among men
      ages 20 to 34 years. Although the pathogenesis of TGCC is poorly understood,
      suboptimal androgen levels or impaired androgen signaling may play a role. Some
      persistent organochlorine pesticides commonly found in human tissue possess
      antiandrogenic properties. We examined whether the risk of TGCC is associated
      with serum levels of 11 organochlorine pesticides, including p,p'-DDE, and
      whether the p,p'-DDE-TGCC association is modified by CAG or GGN repeat
      polymorphisms in the androgen receptor gene. We conducted a population-based case
      control study among 18- to 44-year-old male residents of three Washington State
      counties. Cases (n = 246) were diagnosed during 1999 to 2003 with a first,
      primary TGCC. Controls (n = 630) were men of similar age with no history of TGCC
      from the same population identified through random-digit telephone dialing.
      Questionnaires elicited information on demographic, medical, and lifestyle
      factors. A blood specimen provided serum for gas chromatography-high-resolution
      mass spectrometry analysis of organochlorine pesticide residues and DNA for
      genotyping. We observed no clear patterns between TGCC risk and concentrations of
      any of the organochlorines measured, nor did we observe that the risk associated
      with p,p'-DDE was modified by androgen receptor CAG (<23 versus > or =23 repeats)
      or GGN (<17 versus > or =17 repeats) genotype. This study does not provide
      support for the hypothesis that adult exposure to organochlorine pesticides is
      associated with risk of TGCC. Due to uncertainty regarding how well
      organochlorine levels measured in adulthood reflect exposures during early life,
      further research is needed using exposure measurements collected in utero or
      during infancy.

PMID- 18708394
TI  - Alcohol and breast cancer risk defined by estrogen and progesterone receptor
      status: a case-control study.
AB  - BACKGROUND: Alcohol consumption increases breast cancer risk. Some studies
      suggested that this association is stronger or limited to tumors expressing
      estrogen receptors (ER). METHODS: We investigated the role of alcohol according
      to ER and progesterone receptor (PR) status in a case-control study on breast
      cancer conducted from 1991 to 1994 in three Italian areas. Cases were 989 women
      with incident, histologically confirmed breast cancer. Controls were 1,350 women
      admitted to hospitals in the same catchment areas for acute nonneoplastic
      diseases. A validated food-frequency questionnaire was used to collect
      information on dietary habits and lifetime consumption of various alcoholic
      beverages. Multiple logistic regression models were used to estimate odds ratios
      and 95% confidence interval (95% CI). RESULTS: Alcohol drinking was associated
      with ER+ tumors (odds ratio, 2.16; 95% CI, 1.68-2.76 for an intake of > or =13.8
      g/d as compared with nondrinkers). The odds ratio was 1.13 (95% CI, 1.07-1.20)
      for a 10-g increase in daily intake. For ER- tumors, the relation with alcohol
      consumption was not significant (odds ratio, 1.36; 95% CI, 0.93-2.01). When
      breast cancers were further classified according to PR, the findings for ER+PR+
      cancers were similar to those for all ER+ ones, with an odds ratio of 2.34 (95%
      CI, 1.81-3.04) for an intake of > or =13.8 g/d. No significant association
      emerged for ER-PR- tumors (odds ratio, 1.25; 95% CI, 0.81-1.94). CONCLUSION: This
      study supports the hypothesis that alcohol is more strongly related to ER+ than
      to ER- breast tumors.

PMID- 18708395
TI  - Circulating 2-hydroxy- and 16alpha-hydroxy estrone levels and risk of breast
      cancer among postmenopausal women.
AB  - Circulating estrogens are associated with breast cancer risk in postmenopausal
      women. Given that estrogen metabolites are potentially both mitogenic and
      genotoxic, it is possible that plasma levels of estrogen metabolites are related
      to breast cancer risk. We conducted a prospective, nested case-control study
      within the Nurses' Health Study. Blood samples, collected in 1989 to 1990, were
      assayed for 2-OH and 16alpha-OH estrone among 340 cases and 677 matched controls
      not taking postmenopausal hormones. Multivariate relative risks (RR) and 95%
      confidence intervals (95% CI) were calculated by conditional logistic regression,
      adjusting for breast cancer risk factors. Neither 2-OH nor 16alpha-OH estrone
      concentrations were significantly associated with breast cancer risk overall (top
      versus bottom quartile: RR, 1.19; 95% CI, 0.80-1.79; P(trend) = 0.40 for 2-OH
      estrone and RR, 1.04; 95% CI, 0.71-1.53; P(trend) = 0.81 for 16alpha-OH estrone).
      The ratio between the two metabolites (2-OH:16alpha-OH estrone) was similarly
      unrelated to risk overall (1.30; 95% CI, 0.87-1.95; P(trend) = 0.35). Although no
      associations were detected among women with estrogen receptor (ER)
      positive/progesterone receptor (PR)-positive tumors, significant positive
      associations were observed for 2-OH estrone and the 2-OH:16alpha-OH estrone ratio
      among women with ER-negative/PR-negative tumors (RR, 3.65; 95% CI, 1.23-10.81;
      P(trend) = 0.01; P(heterogeneity) = 0.02 for 2-OH estrone; RR, 3.70; 95% CI, 1.24
      11.09; P(trend) = 0.004; P(heterogeneity) = 0.005 for 2-OH:16alpha-OH estrone).
      These data do not support the hypothesized inverse associations with 2-OH estrone
      and the 2-OH:16alpha-OH estrone ratio or the hypothesized positive association
      with 16alpha-OH estrone. The significant positive associations with 2-OH estrone
      and the 2-OH:16-OH estrone ratio among women with ER-negative/PR-negative tumors
      needs to be replicated in future studies.

PMID- 18708396
TI  - The human papillomavirus infection in men study: human papillomavirus prevalence
      and type distribution among men residing in Brazil, Mexico, and the United
      States.
AB  - Male sexual behavior influences the rates of cervical dysplasia and invasive
      cervical cancer, as well as male human papillomavirus (HPV) infection and
      disease. Unfortunately, little is known regarding male HPV type distribution by
      age and across countries. In samples combined from the coronal sulcus, glans
      penis, shaft, and scrotum of 1,160 men from Brazil, Mexico, and the United
      States, overall HPV prevalence was 65.2%, with 12.0% oncogenic types only, 20.7%
      nononcogenic types only, 17.8% both oncogenic and nononcogenic, and 14.7%
      unclassified infections. Multiple HPV types were detected in 25.7% of study
      participants. HPV prevalence was higher in Brazil (72.3%) than in the United
      States (61.3%) and Mexico (61.9%). HPV16 (6.5%), HPV51 (5.3%), and HPV59 (5.3%)
      were the most commonly detected oncogenic infections, and HPV84 (7.7%), HPV62
      (7.3%), and HPV6 (6.6%) were the most commonly detected nononcogenic infections.
      Overall HPV prevalence was not associated with age. However, significant
      associations with age were observed when specific categories of HPV,
      nononcogenic, and unclassified HPV infections were considered. Studies of HPV
      type distribution among a broad age range of men from multiple countries is
      needed to fill the information gap internationally with respect to our knowledge
      of HPV infection in men.

PMID- 18708397
TI  - Phenotype comparison of MLH1 and MSH2 mutation carriers in a cohort of 1,914
      individuals undergoing clinical genetic testing in the United States.
AB  - BACKGROUND AND AIMS: Lynch syndrome is caused by germ-line mismatch repair gene
      mutations. We examined the phenotypic differences between MLH1 and MSH2 gene
      mutation carriers and whether mutation type (point versus large rearrangement)
      affected phenotypic expression. METHODS: This is a cross-sectional prevalence
      study of 1,914 unrelated probands undergoing clinical genetic testing for MLH1
      and MSH2 mutations at a commercial laboratory. RESULTS: Fifteen percent (285 of
      1,914) of subjects had pathogenic mutations (112 MLH1, 173 MSH2). MLH1 carriers
      had a higher prevalence of colorectal cancer (79% versus 69%, P = 0.08) and
      younger mean age at diagnosis (42.2 versus 44.8 years, P = 0.03) than MSH2
      carriers. Forty-one percent of female carriers had endometrial cancer and
      prevalence was similar in both groups. Other cancers were more frequent in MSH2
      carriers (24% versus 9%, P = 0.001) and their families (P < 0.001). Multivariable
      analyses confirmed these associations. Of the 1,016 subjects who underwent
      Southern blot analysis, 42 had large rearrangements (7 MLH1, 35 MSH2). There were
      no phenotypic differences between carriers with large rearrangements and point
      mutations. CONCLUSIONS: In this large study of mismatch repair gene mutation
      carriers from the United States, MLH1 carriers had more colorectal cancer than
      MSH2 carriers whereas endometrial cancer prevalence was similar. Large genomic
      rearrangements were more frequent in the MSH2 gene. MSH2 carriers and their
      relatives have more extracolonic nonendometrial Lynch syndrome-associated cancers
      and may benefit from additional screening.

PMID- 18708399
TI  - Association between common genetic variation in Cockayne syndrome A and B genes
      and nucleotide excision repair capacity among smokers.
AB  - Mutagen sensitivity in in vitro cultured lymphocytes challenged by benzo[a]pyrene
      diolepoxide (BPDE) has been validated as an intrinsic susceptibility factor for
      several cancers. Bulky BPDE-DNA adducts are repaired via either transcription
      coupled repair or global genome nucleotide excision repair depending on the
      location of lesions. Cockayne syndrome A (CSA) and B (CSB) play essential roles
      in integrating the recognition of damage, chromatin remodeling, and the core
      nucleotide excision repair proteins. This study evaluated the hypothesis that
      common genetic variation in CSA and CSB is associated with mutagen sensitivity
      induced by BPDE in 276 cancer-free smokers. Tag single nucleotide polymorphisms
      (SNP; n = 37) selected across the entire coding and putative regulatory regions
      of CSA and CSB based on a high-density SNP database were genotyped by the
      Illumina Golden Gate assay. Major principal components of CSA and CSB that
      captured the linkage disequilibrium from multiple SNPs were globally associated
      with the number of breaks per cell at the threshold of 80% (P < or = 0.02 for
      both genes). Haplotype H125 in CSA and H97 in CSB as well as SNPs in high linkage
      disequilibrium with these two haplotypes were significantly associated with a 13%
      to 15% reduction in the mean number of chromatid breaks per cell (P < 0.05). A
      resampling-based omnibus test supported the significant association between SNPs
      and haplotypes in CSA and mutagen sensitivity induced by BPDE (P = 0.035). This
      study implicates transcription-coupled repair in protecting the cell from BPDE
      induced DNA damage.

PMID- 18708398
TI  - Multiple novel prostate cancer predisposition loci confirmed by an international
      study: the PRACTICAL Consortium.
AB  - A recent genome-wide association study found that genetic variants on chromosomes
      3, 6, 7, 10, 11, 19 and X were associated with prostate cancer risk. We evaluated
      the most significant single-nucleotide polymorphisms (SNP) in these loci using a
      worldwide consortium of 13 groups (PRACTICAL). Blood DNA from 7,370 prostate
      cancer cases and 5,742 male controls was analyzed by genotyping assays. Odds
      ratios (OR) associated with each genotype were estimated using unconditional
      logistic regression. Six of the seven SNPs showed clear evidence of association
      with prostate cancer (P = 0.0007-P = 10(-17)). For each of these six SNPs, the
      estimated per-allele OR was similar to those previously reported and ranged from
      1.12 to 1.29. One SNP on 3p12 (rs2660753) showed a weaker association than
      previously reported [per-allele OR, 1.08 (95% confidence interval, 1.00-1.16; P =
      0.06) versus 1.18 (95% confidence interval, 1.06-1.31)]. The combined risks
      associated with each pair of SNPs were consistent with a multiplicative risk
      model. Under this model, and in combination with previously reported SNPs on 8q
      and 17q, these loci explain 16% of the familial risk of the disease, and men in
      the top 10% of the risk distribution have a 2.1-fold increased risk relative to
      general population rates. This study provides strong confirmation of these
      susceptibility loci in multiple populations and shows that they make an important
      contribution to prostate cancer risk prediction.

PMID- 18708400
TI  - Genetic polymorphisms in the Paraoxonase 1 gene and risk of ovarian epithelial
      carcinoma.
AB  - Oxidative stress during successive ovulations increases the opportunity for DNA
      damage to ovarian epithelial cells and the potential for malignant
      transformation. Paraoxonase 1 (PON1) is an endogenous free radical scavenger that
      reduces oxidative stress. The association of two common functional single
      nucleotide polymorphisms (SNP), rs854560 T>A and rs662 A>G, with the risk of
      epithelial ovarian cancer was examined in a population-based case-control study
      in Hawaii. A personal interview and blood specimens were collected from 274 women
      with histologically confirmed, primary ovarian cancer and 452 controls frequency
      matched on age and ethnicity. Odds ratios (OR) and 95% confidence intervals (95%
      CI) were estimated by unconditional logistic regression. Both PON1 SNPs were
      significantly associated with ovarian cancer risk. The ORs were 0.53 (95% CI,
      0.35-0.79; P for allele-dose effect = 0.01) for women carrying the rs854560 T
      allele compared with women with the AA genotype and 0.65 (95% CI, 0.44-0.95; P
      for allele-dose effect = 0.03) for women carrying the rs662 A allele compared
      with women with the GG genotype. The association of the rs854560 T genotype with
      risk was stronger among smokers (OR, 0.33; 95% CI, 0.17-0.64; P for allele-dose
      effect = 0.0007) than among nonsmokers (OR, 0.68; 95% CI, 0.40-1.18; P for allele
      dose effect = 0.53). The decreased risk associated with the rs854560 T allele was
      also stronger among obese women (OR, 0.19; 95% CI, 0.06-0.55; P for allele-dose
      effect = 0.007) than among nonobese women (OR, 0.62; 95% CI, 0.40-0.98; P for
      allele-dose effect = 0.16). Our study provides evidence for an association of two
      PON1 SNPs with the risk of epithelial ovarian cancer. Possible effect
      modification of these associations by tobacco smoking and obesity needs
      confirmation in other studies.

PMID- 18708401
TI  - Does pretreatment seropositivity to human papillomavirus have prognostic
      significance for head and neck cancers?
AB  - BACKGROUND: Human papillomavirus (HPV) is a risk factor for head and neck cancers
      (HNC), yet HPV-associated tumors have better prognosis than HPV-negative tumors.
      METHODS: We evaluated whether pretreatment presence of antibodies to HPV capsids
      [virus-like particles (VLP)] or to HPV-16 oncoproteins E6 and E7 was a predictor
      of HPV-positive HNC and clinical outcomes. Sera from 156 HNC patients were tested
      for antibodies to HPV-16-derived antigens using ELISA. HPV-16 in tumors was
      evaluated by PCR and DNA sequencing. RESULTS: HPV-16 antibodies were found in 33%
      with HPV-16 VLP, 21% with HPV-16 E6, and 21% with E7. HPV-16 was detected in 26%
      of tumors. There was a strong correlation between detection of HPV-16 tumor DNA
      and antibodies to HPV-16 E6 or E7 (kappa = 0.7) but not to HPV-16 VLP (kappa =
      0.4). Multivariate analyses showed significantly better disease-specific survival
      in seropositive HPV-16 VLP [hazard ratio (HR), 0.4; 95% confidence interval (95%
      CI), 0.1-0.9], HPV-16 E6 (HR, 0.1; 95% CI, 0.02-0.5), and HPV-16 E7 (HR, 0.3; 95%
      CI, 0.1-0.9) cases. Less disease recurrence occurred among those with antibodies
      to both E6 and E7 compared with those negative to both (P = 0.003). There was
      better disease-specific survival in patients who were E6 positive at baseline and
      remained positive at follow-up compared with individuals who were E6 negative at
      both time points (P = 0.03; kappa = 0.9). CONCLUSIONS: The presence of antibodies
      to HPV-16 E6 and E7 is associated with HPV in tumor cells and with better
      clinical outcomes. These findings suggest that the presence of E6/E7 antibodies
      before treatment is predictive of better clinical outcomes and that they may
      serve as biomarkers for selecting targeted therapeutic modalities developed for
      HPV-associated tumors.

PMID- 18708402
TI  - Nested case-control study of the association of circulating levels of serum
      insulin-like growth factor I and insulin-like growth factor binding protein 3
      with breast cancer in young women in Norway.
AB  - BACKGROUND: High circulating levels of insulin-like growth factor (IGF-I) may
      elevate the risk of breast cancer in premenopausal women, possibly by increasing
      cell proliferation and reducing apoptosis. METHODS: We conducted a nested case
      control study among 35,105 Norwegian women who participated in a health screening
      survey, ages 40 to 42 years, and who were subsequently followed for a mean period
      of 4.3 years. During this period, 325 women were diagnosed with breast cancer;
      647 women without breast cancer, matched on age and time of blood sampling, were
      selected as controls. Serum concentrations of IGF-I and its main binding protein
      (IGFBP-3) were measured with radioimmunoassay, and logistic regression analysis
      was used to adjust for relevant covariates. RESULTS: The mean age at blood
      collection was 41.1 years in both groups, and the mean age at diagnosis for the
      cases was 45.4 years (range, 40-51 years). The median IGF-I level did not differ
      between cases (205 ng/mL) and controls (202 ng/mL). When analyzed by categories
      of serum IGF-I, the relative risk for women in the highest versus the lowest
      quintile was 1.46 (95% confidence interval, 0.93-2.32; P(trend) = 0.15) after
      adjusting for serum IGFBP-3, age, and year of blood collection. The exclusion of
      cases that were diagnosed within 2 years after blood collection did not
      materially affect the results. CONCLUSION: We found only a modest positive
      association between serum IGF-I levels and risk of breast cancer in women younger
      than 50 years of age.

PMID- 18708403
TI  - Association of genetic variation in genes implicated in the beta-catenin
      destruction complex with risk of breast cancer.
AB  - Aberrant Wnt/beta-catenin signaling leading to nuclear accumulation of the
      oncogene product beta-catenin is observed in a wide spectrum of human
      malignancies. The destruction complex in the Wnt/beta-catenin pathway is critical
      for regulating the level of beta-catenin in the cytoplasm and in the nucleus.
      Here, we report a comprehensive study of the contribution of genetic variation in
      six genes encoding the beta-catenin destruction complex (APC, AXIN1, AXIN2,
      CSNK1D, CSNK1E, and GSK3B) to breast cancer using a Mayo Clinic Breast Cancer
      Case-Control Study. A total of 79 candidate functional and tagging single
      nucleotide polymorphisms (SNP) were genotyped in 798 invasive cases and 843
      unaffected controls. Of these, rs454886 in the APC tumor suppressor gene was
      associated with increased breast cancer risk (per allele odds ratio, 1.23; 95%
      confidence intervals, 1.05-1.43; P(trend) = 0.01). In addition, five SNPs in
      AXIN2 were associated with increased risk of breast cancer (P(trend) < 0.05).
      Haplotype-based tests identified significant associations between specific
      haplotypes in APC and AXIN2 (P < or = 0.03) and breast cancer risk. Further
      characterization of the APC and AXIN2 variants suggested that AXIN2 rs4791171 was
      significantly associated with risk in premenopausal (P(trend) = 0.0002) but not
      in postmenopausal women. The combination of our findings and numerous genetic and
      functional studies showing that APC and AXIN2 perform crucial tumor suppressor
      functions suggest that further investigation of the contribution of AXIN2 and APC
      SNPs to breast cancer risk are needed.

PMID- 18708404
TI  - B-vitamin intake, one-carbon metabolism, and survival in a population-based study
      of women with breast cancer.
AB  - Breast cancer is the second leading cause of cancer mortality among women. Given
      its important role in DNA methylation and synthesis, one-carbon metabolism may
      affect breast cancer mortality. We used a population-based cohort of 1,508 women
      with breast cancer to investigate possible associations of dietary intake of B
      vitamins before diagnosis as well as nine polymorphisms of one-carbon
      metabolizing genes and subsequent survival. Women newly diagnosed with a first
      primary breast cancer in 1996 to 1997 were followed for vital status for an
      average of 5.6 years. Kaplan-Meier survival and Cox proportional hazard
      regression analyses were used to evaluate the association between dietary intakes
      of B vitamins (1,479 cases), genotypes ( approximately 1,065 cases), and all
      cause as well as breast cancer-specific mortality. We found that higher dietary
      intake of vitamin B(1) and B(3) was associated with improved survival during the
      follow-up period (P(trend) = 0.01 and 0.04, respectively). Compared with the
      major genotype, the MTHFR 677 T allele carriers have reduced all-cause mortality
      and breast cancer-specific mortality in a dominant model [hazard ratio (95%
      confidence interval): 0.69 (0.49-0.98) and 0.58 (0.38-0.89), respectively]. The
      BHMT 742 A allele was also associated with reduced all-cause mortality [hazard
      ratio, 0.70 (0.50-1.00)]. Estrogen receptor/progesterone receptor status modified
      the association between the MTHFR C677T polymorphism and survival (P = 0.05). The
      survival associations with one-carbon polymorphisms did not differ with the use
      of chemotherapy, although study power was limited for examining such effect
      modification. Our results indicate that one-carbon metabolism may be an important
      pathway that could be targeted to improve breast cancer survival.

PMID- 18708406
TI  - Variants of DNA repair genes and the risk of biliary tract cancers and stones: a
      population-based study in China.
AB  - Biliary tract cancers, which encompass tumors of the gallbladder, extrahepatic
      ducts, and ampulla of Vater, are relatively rare tumors with a high fatality
      rate. Other than a close link with gallstones, the etiology of biliary tract
      cancers is poorly understood. We conducted a population-based case-control study
      in Shanghai, China, to examine whether genetic variants in several DNA repair
      genes are associated with biliary tract cancers or biliary stones. Genomic DNA
      from 410 patients with biliary tract cancers (236 gallbladder, 127 bile duct, and
      47 ampulla of Vater), 891 patients with biliary stones, and 786 healthy subjects
      randomly selected from the Shanghai population were genotyped for putative
      functional single nucleotide polymorphisms in four DNA repair genes (MGMT,
      RAD23B, CCNH, and XRCC3). Of the five single nucleotide polymorphisms examined,
      only one (MGMT EX5-25C>T, rs12917) was associated with biliary tract cancer.
      Independent of gallstones, subjects carrying the CT genotype of the MGMT EX5
      25C>T marker had a significantly reduced risk of gallbladder cancer [odds ratio
      (OR), 0.63; 95% confidence interval (95% CI), 0.41-0.97; P = 0.02] and
      nonsignificant reduced risks of bile duct (OR, 0.61; 95% CI, 0.35-1.06) and
      ampulla of Vater (OR, 0.85; 95% CI, 0.39-1.87) cancers. However, this marker was
      not associated with biliary stones, and the other markers examined were not
      significantly associated with either biliary tract cancers or stones. Findings
      from this population-based study in Shanghai suggest that MGMT gene variants may
      alter susceptibility to biliary tract cancer, particularly gallbladder cancer.
      Confirmation in future studies, however, is required.

PMID- 18708405
TI  - Association of mitochondrial DNA displacement loop (CA)n dinucleotide repeat
      polymorphism with breast cancer risk and survival among Chinese women.
AB  - Mitochondrial genome alternations may be involved in carcinogenesis. The
      noncoding region of the mitochondrial DNA (mtDNA) displacement loop (D-loop) has
      emerged as a mutational hotspot. Using data from a population-based case-control
      study conducted among Chinese women in Shanghai, we evaluated associations of
      breast cancer risk and survival with the mtDNA D-loop (CA)(n) dinucleotide repeat
      polymorphism. Included in the study were 1,058 cases and 1,129 age frequency
      matched community controls that participated in the Shanghai Breast Cancer Study
      between 1996 and 1998. Breast cancer patients were followed to determine
      intervals of overall survival and disease-free survival. Overall, there was no
      association between the mtDNA D-loop (CA)(n) repeat polymorphism and breast
      cancer risk. Patients with multiple alleles of the mtDNA D-loop (CA)(n)
      polymorphism (heteroplasmy) had significantly poorer disease-free survival than
      those with one allele of the mtDNA D-loop (CA)(n) polymorphism (hazard ratio
      1.62; 95% confidence interval, 1.16-2.26). These results suggest that the mtDNA D
      loop (CA)(n) repeat polymorphism may be associated with breast cancer survival.
      Additional studies with a larger sample size are warranted.

PMID- 18708407
TI  - Dietary soy and isoflavone intake and risk of colorectal cancer in the Japan
      public health center-based prospective study.
AB  - Several experimental studies have reported that the anticarcinogenic properties
      of dietary soy play an important role in preventing colorectal cancer. However,
      few epidemiologic studies have examined this association in general populations
      and their findings have been inconsistent. We investigated the association
      between dietary soy and isoflavone intake and incidence of colorectal cancer in a
      prospective cohort study of 83,063 Japanese men and women, ages 45 to 74 years.
      Dietary soy and isoflavone intake was measured through a validated food frequency
      questionnaire in 1995 and 1998. Throughout 2004, a total of 886 cases of
      colorectal cancer were newly identified (291 proximal colon, 286 distal colon,
      and 277 rectum). The hazard ratios and 95% confidence intervals (95% CIs) were
      estimated by fitting a Cox proportional hazards model. The intake of isoflavones,
      miso soup, and soy food was not associated with colorectal cancer in either men
      or women. By colorectal cancer subsite, the risk of proximal colon cancer in men
      decreased with increasing consumption of isoflavones, miso soup, and soy food.
      Compared with men in the lowest quartiles of isoflavones, miso soup, and soy food
      intake, the hazard ratios in the highest quartiles were 0.55 (95% CI, 0.33-0.92),
      0.72 (95% CI, 0.43-1.21), and 0.51 (95% CI, 0.30-0.87), respectively. The results
      showed no association for distal colon and rectal cancer in men or for subsites
      of colorectal cancer in women. These findings suggest that the intake of
      isoflavones, miso soup, and soy food has no substantial effect on the risk of
      colorectal cancer in Japanese men and women.

PMID- 18708408
TI  - Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized
      trial of aspirin use and folic acid supplementation.
AB  - BACKGROUND: Folate, other vitamin B cofactors, and genes involved in folate
      mediated one-carbon metabolism all may play important roles in colorectal
      neoplasia. In this study, we examined the associations between dietary and
      circulating plasma levels of vitamins B(2), B(6), and B(12) and risk colorectal
      adenomas. METHODS: The Aspirin/Folate Polyp Prevention Study is a randomized
      clinical trial of folic acid supplementation and incidence of new colorectal
      adenomas in individuals with a history of adenomas (n = 1,084). Diet and
      supplement use were ascertained through a food frequency questionnaire
      administered at baseline. Blood collected at baseline was used to determine
      plasma B-vitamin levels. We used generalized linear regression to estimate risk
      ratios (RR) and 95% confidence intervals (95% CI) as measures of association.
      RESULTS: We found a borderline significant inverse association with plasma B(6)
      [pyridoxal 5'-phosphate (PLP)] and adenoma risk (adjusted RR Q4 versus Q1, 0.78;
      95% CI, 0.61-1.00; P(trend) = 0.08). This association was not modified by folic
      acid supplementation or plasma folate. However, the protective association of PLP
      with adenoma risk was observed only among subjects who did not drink alcohol
      (P(interaction) = 0.03). Plasma B(2) (riboflavin) was inversely associated with
      risk of advanced lesions (adjusted RR Q4 versus Q1, 0.51; 95% CI, 0.26-0.99;
      P(trend) = 0.12). No significant associations were observed between adenoma risk
      and plasma vitamin B(12) or dietary intake of vitamin B(2) and B(6). When we
      examined specific gene-B-vitamin interactions, we observed a possible interaction
      between methylenetetrahydrofolate reductase -C677T and plasma B(2) on risk of all
      adenomas. CONCLUSION: Our results suggest that high levels of PLP and B(2) may
      protect against colorectal adenomas.

PMID- 18708409
TI  - Self-sampling for human papillomavirus in a community setting: feasibility in
      Hispanic women.
AB  - BACKGROUND: The aim of the study was (a) to assess sensitivity and specificity of
      self-sampling in a community setting for identifying high-risk human
      papillomavirus (HPV) infection and abnormal Papanicolaou (Pap) smears and (b) to
      assess satisfaction with this collection method among Hispanic women. METHODS:
      Lay health workers distributed self-collection kits to Hispanic women in the
      community. Participants collected an unsupervised vaginal sample at home or in
      the place and time of their preference. RESULTS: A total of 1,213 Hispanics were
      included and provided a self-sample for HPV testing and were invited for a Pap
      smear; 662 (55%) of them had a Pap smear and the first 386 of these also had a
      physician-collected sample for HPV retesting. Using physician collection as the
      gold standard, unsupervised self-collection had a sensitivity of 90% and
      specificity of 88% for identifying high-risk HPV. Compared with physician
      sampling, self-sampling in a community setting had comparable sensitivity for
      identifying a low-grade lesions or greater in the Pap smear (50% versus 55%; P =
      0.45) but lower specificity (94% versus 79%). Overall experience with self
      sampling was reported as excellent or very good by 64% and only 2.6% reported a
      poor or fair experience. CONCLUSIONS: Unsupervised self-collection of vaginal
      samples for HPV testing in a community setting has a high sensitivity for
      identifying high-risk HPV and a high satisfaction among Hispanics. This approach
      may benefit populations with limited access to health care or with cultural
      barriers to cervical cancer screening.

PMID- 18708410
TI  - Effect of language on colorectal cancer screening among Latinos and non-Latinos.
AB  - BACKGROUND: Language barriers among some Latinos may contribute to the lower
      rates of colorectal cancer (CRC) screening between Latinos and non-Latino Whites.
      The purpose of this study was to examine the relationship between language and
      receipt of CRC screening tests among Latinos and non-Latinos using a
      geographically diverse, population-based sample of adults. METHODS: Cross
      sectional analysis of the Behavioral Risk Factor Surveillance System (BRFSS)
      survey. Analysis included adults age 50 years and older, who completed the 2006
      BRFSS in a state that recorded data from English- and Spanish-speaking
      participants. RESULTS: The primary outcome measure was receipt of colorectal
      screening tests (fecal occult blood testing within prior 12 months and/or lower
      endoscopy within 10 years). Of the 99,895 respondents included in the study
      populations, 33% of Latinos responding-in-Spanish reported having had CRC
      testing, whereas 51% of Latinos responding-in-English and 62% of English-speaking
      non-Latinos reported test receipt. In multivariable analysis, compared with non
      Latinos, Latinos responding-in-English were 16% less likely to have received CRC
      testing [odds ratio (OR), 0.84; 95% confidence interval (95% CI), 0.73-0.98], and
      Latinos responding-in-Spanish were 43% less likely to have received CRC testing
      (OR, 0.57; 95% CI, 0.44-0.74). Additionally, compared with Latinos responding-in
      English, Latinos responding-in-Spanish were 36% less likely to have received CRC
      testing (OR, 0.64; 95% CI, 0.48-0.84). CONCLUSION: Latinos responding to the 2006
      BRFSS survey in Spanish had a significantly lower likelihood of receiving CRC
      screening tests compared with non-Latinos and to Latinos responding-in-English.
      Based on this analysis, Spanish language use is negatively associated with CRC
      screening and may contribute to disparities in CRC screening.

PMID- 18708411
TI  - p16 Promoter methylation is a potential predictor of malignant transformation in
      oral epithelial dysplasia.
AB  - Management of the patient with oral epithelial dysplasia depends on the ability
      to predict malignant transformation. Histologic grading of this condition fails
      in this regard and is also subject to interpathologist and intrapathologist
      variability. This study uses longitudinal clinical samples to explore the
      prognostic value of a previously validated panel of methylation biomarkers in a
      cohort of patients with histologically proven oral dysplasia. Methylation
      enrichment pyrosequencing assays were used to provide the sensitivity of
      traditional methylation-specific PCR with the additional specificity advantages
      of a subsequent confirmatory sequencing reaction. In 57% (8 of 14) patients with
      a lesion that transformed to oral squamous cell carcinoma, 26% (26 of 100) of
      longitudinal samples collected over > or =3 years showed p16 methylation. Only 1%
      (2 of 184) of samples from 8% of patients (2 of 24) not undergoing malignant
      transformation within 3 years had p16 methylation. Both of these samples with p16
      promoter methylation were the most recently collected and the patients remain
      under continuing clinical review. Promoter methylation of MGMT, CYGB, and CCNA1
      did not correlate with malignant progression. We thus conclude that methylation
      of the p16 gene promoter shows promise as a predictor for malignant
      transformation (Fisher's exact, P = 0.002) in a subset of patients.

PMID- 18708412
TI  - Circulating human interleukin-8 as an indicator of cancer progression in a nude
      rat orthotopic human non-small cell lung carcinoma model.
AB  - Clinically relevant animal models of human cancer are necessary for the
      evaluation of putative therapeutics. We hypothesized that circulating human lung
      cancer-associated proteins would correlate with physiologic measurements from an
      orthotopic H460 human non-small cell lung carcinoma model that we developed in
      immunodeficient rats. Physiologic measurements and serum samples were collected
      over time. Serum interleukin-8 (IL-8), p53, vascular endothelial growth factor,
      and matrix metalloproteinase-9 were quantitated for correlation with physiologic
      measurements. Matrix metalloproteinase-9 and p53 were not significantly
      detectable. Circulating vascular endothelial growth factor was detected at high
      levels in some tumor-bearing animals. Human IL-8 was detectable in all tumor
      bearing animals and correlated positively with markers of respiratory acidosis
      (pH, P = 0.012; TCO(2), P = 0.024; pCO(2), P = 0.007; and HCO(3)(-), P = 0.029)
      and with surface body temperature (P = 0.001) beginning on day 16 after
      implantation. IL-8 levels negatively correlated with survival (P < 0.001),
      indicating an association with tumor burden. Circulating human IL-8 might be a
      useful, clinically relevant circulating tumor protein marker due to its positive
      correlation with multiple physiologic variables associated with lung cancer
      progression.

PMID- 18708413
TI  - Assessment of serum proteomics to detect large colon adenomas.
AB  - A noninvasive blood test that could reliably detect early colorectal cancer or
      large adenomas would provide an important advance in colon cancer screening. The
      purpose of this study was to determine whether a serum proteomics assay could
      discriminate between persons with and without a large (> or =1 cm) colon adenoma.
      To avoid problems of "bias" that have affected many studies about molecular
      markers for diagnosis, specimens were obtained from a previously conducted study
      of colorectal cancer etiology in which bloods had been collected before the
      presence or absence of neoplasm had been determined by colonoscopy, helping to
      assure that biases related to differences in sample collection and handling would
      be avoided. Mass spectra of 65 unblinded serum samples were acquired using a
      nanoelectrospray ionization source on a QSTAR-XL mass spectrometer.
      Classification patterns were developed using the ProteomeQuest algorithm,
      performing measurements twice on each specimen, and then applied to a blinded
      validation set of 70 specimens. After removing 33 specimens that had discordant
      results, the "test group" comprised 37 specimens that had never been used in
      training. Although in the primary analysis, no discrimination was found, a single
      post hoc analysis, done after hemolyzed specimens had been removed, showed a
      sensitivity of 78%, a specificity of 53%, and an accuracy of 63% (95% confidence
      interval, 53-72%). The results of this study, although preliminary, suggest that
      further study of serum proteomics, in a larger number of appropriate specimens,
      could be useful. They also highlight the importance of understanding sources of
      "noise" and "bias" in studies of proteomics assays.

PMID- 18708414
TI  - Metastatic gastrointestinal stromal tumors in the era of imatinib: improved
      survival and elimination of socioeconomic survival disparities.
AB  - BACKGROUND: Imatinib was approved in 2002 for unresectable and metastatic
      gastrointestinal stromal tumors. Our objective was to determine if the
      introduction of imatinib coincided with improved survival from metastatic
      gastrointestinal stromal tumor in the U.S. population and in specific
      socioeconomic groups. METHODS: Query of the Surveillance, Epidemiology, and End
      Results registry identified 552 patients with metastatic gastrointestinal stromal
      tumor between 1995 and 2004. Year of diagnosis was categorized into two periods,
      1995 to 2000 and 2001 to 2004, to account for the effect of imatinib. Kaplan
      Meier and multivariate Cox regression analyses were used to examine differences
      in survival between periods and among socioeconomic groups. RESULTS: Median
      survival increased from 12 to 33 months from 1995 to 2000 to 2001 to 2004 (P <
      0.001); survival at 47 months increased from 21% to 41%, respectively (P <
      0.001). Median survival times for White, Black, Hispanic, and Asian or Pacific
      Islander, and for low-, middle-, and high-income groups increased significantly
      in the era of imatinib (all P < 0.05). On multivariate analysis, Black race
      [hazard ratio, 1.96; 95% confidence interval (95% CI), 1.15-3.32; P = 0.013],
      Hispanic race (hazard ratio, 2.11; 95% CI, 1.14-3.88; P = 0.017), and low income
      (hazard ratio, 1.81; 95% CI, 1.13-2.89; P = 0.014) were associated with the
      poorest survival during the 1995 to 2000 period. During 2001 to 2004, these
      disparities in survival were no longer statistically apparent. CONCLUSIONS:
      Survival from metastatic gastrointestinal stromal tumor has improved
      significantly in the era of imatinib. This improvement has been uniform across
      all socioeconomic groups, with concomitant elimination of socioeconomic survival
      disparities potentially due to an assistance program intended to provide
      universal access to imatinib therapy.

PMID- 18708415
TI  - Mechanisms of bone erosion in gout: a quantitative analysis using plain
      radiography and computed tomography.
AB  - OBJECTIVE: The underlying basis of bone erosion in gout remains speculative. The
      aim of this study was to understand the mechanisms of bone erosion in gout using
      non-invasive imaging techniques. METHODS: Paired plain radiographs and computed
      tomography (CT) scans of 798 individual hand and wrist joints from 20 patients
      with gout were analysed. Radiographs were scored for erosion (0-5) using the
      Sharp/van der Heijde method. CT scans were scored for the presence and diameter
      of bone erosions and tophi. The presence of intraosseous tophus (tophus
      visualised within bone) was recorded. The relationships between radiographic
      erosion, CT erosion and tophus scores were analysed. RESULTS: With increasing
      radiographic erosion scores, the percentage of joints with intraosseous tophus
      increased (p<0.001). For those joints with a radiographic erosion score of 4 or
      5, 96/98 (98%) had CT evidence of intraosseous tophus. There was a significant
      relationship between the radiographic erosion scores and intraosseous tophus size
      (p<0.001). For those joints with CT erosion, 194/237 (81.8%) had visible
      intraosseous tophus. Of the joints with CT erosions greater than 5 mm, 106/112
      (94.6%) had visible intraosseous tophus and all (56/56) erosions greater than 7.5
      mm had intraosseous tophus. There was a strong correlation between CT erosion
      diameter and intraosseous tophus diameter (r = 0.93, p<0.001). Intraosseous tophi
      were larger than non-intraosseous tophi, but had similar density and
      calcification. CONCLUSION: There is a strong relationship between bone erosion
      and the presence of intraosseous tophus. These results strongly implicate tophus
      infiltration into bone as the dominant mechanism for the development of bone
      erosion and joint damage in gout.

PMID- 18708416
TI  - Management of congenital cystic adenomatous malformations of the lung.
AB  - Congenital cystic adenomatous malformation of the lung (CCAM) is a rare lung
      lesion easily diagnosed on prenatal scan. The pathology of fetal lesions differs
      from postnatal lesion, hence the need for separate classifications during the
      different stages of development. Fetuses with CCAMs and hydrops have a poor
      prognosis and may be candidates for prenatal intervention where available. Most
      prenatally diagnosed CCAMs have a favourable outcome. Early surgery is required
      for symptomatic babies. Management of prenatally diagnosed asymptomatic lesions
      remains controversial, with the options of conservative management with CT scan
      surveillance or surgical excision. Surgical excision is favoured by many centres
      because of the risk of infection and malignant transformation if the CCAM remains
      in situ. Surgical outcomes are excellent.

PMID- 18708417
TI  - Impaired left ventricular energy metabolism in patients with hypertrophic
      cardiomyopathy is related to the extension of fibrosis at delayed gadolinium
      enhanced magnetic resonance imaging.
AB  - OBJECTIVE: Areas of intramyocardial late enhancement (LE) at delayed enhanced
      magnetic resonance imaging (DE-MRI) and reduction of myocardial phosphocreatine
      (PCr)/ATP-ratio at phosphorus magnetic resonance spectroscopy ((31)P-MRS) are
      both reported in hypertrophic cardiomyopathy (HCM) and indicate areas of
      increased interstitial myocardial space with fibrosis and impairment of
      myocardial energy metabolism, respectively. We sought to ascertain whether in HCM
      patients the abnormal features of left ventricular (LV) interstitial space
      revealed by DE-MRI correlated with impaired LV energy metabolism shown at (31)P
      MRS. METHODS: 19 patients with HCM proved by histological analysis of multiple
      endomyocardial biopsies and with normal coronary arteries, underwent cardiac MRI
      including DE-MRI and (31)P-MRS. DE-MRI for detection and quantification of late
      enhancement (LE) and (31)P-MRS to assess the myocardial PCr/ATP-ratio were
      performed by means of a 1.5-T magnet. 19 healthy subjects, matched for gender and
      age were studied by (31)P-MRS as control group. RESULTS: LE areas in the LV wall
      were found in 17 out of 19 patients with an extension ranging from 0.8% to 19.5%
      of the LV-mass (mean value 7.6% (SD 5.6%). The PCr/ATP-ratio was lower in HCM
      patients than in control subjects (2.18 (0.41) vs 2.41 (0.30); p<0.05). LE% and
      PCr/ATP-ratio were inversely related (R = -0.57; p<0.05) and LE% was the stronger
      predictor of PCr/ATP-ratio by multivariate analysis. CONCLUSIONS: This study
      demonstrated that the known alteration of the PCr/ATP-ratio observed in HCM
      patients is correlated with the presence of fibrotic areas in the myocardium of
      the left ventricle.

PMID- 18708418
TI  - Is it cardiac? Assessment of syncope with a scoring system.

PMID- 18708419
TI  - Age threshold for vascular prophylaxis by aspirin in patients without diabetes.
AB  - OBJECTIVE: To determine an appropriate age threshold at which to prescribe
      aspirin for primary cardiovascular disease (CVD) prevention among men and women
      without diabetes. DESIGN: Cross-sectional study. SETTING: 304 general practices
      in England and Wales contributing to The Health Improvement Network (THIN)
      electronic patient files. PARTICIPANTS: Subjects aged between 30 and 75 years
      without diabetes, not prescribed any lipid-lowering treatment and with no
      previous history of CVD. Subjects had to have been registered by their practices
      for the whole of the preceding 12 months to be included in the analysis. OUTCOMES
      MEASURES: Relation between age and coronary heart disease (CHD) risk, and the age
      threshold at which subjects without diabetes develop an estimated 10-year CHD
      risk of >or=10%. RESULTS: The age transition from <10% to >10%, 10-year CHD risk
      for men and women without diabetes occurred at ages 47.8 for men and 57.3 for
      women. CONCLUSIONS: In the absence of significant bleeding risks, aspirin should
      routinely be considered for all men and women without diabetes above the ages of
      48 and 57 years, respectively, for primary CVD prevention. For subjects below
      these age thresholds or for those above the age of 75 years, the decision to
      initiate aspirin should be based on a patient's individual cardiovascular risk
      profiles. These proposed age thresholds aim to take into account a patient's
      gender, bleeding risk and the cardioprotective benefits of low-dose aspirin
      treatment.

PMID- 18708420
TI  - Routine use of oxygen in the treatment of myocardial infarction: systematic
      review.
AB  - CONTEXT: International guidelines recommend the routine use of oxygen therapy in
      the treatment of myocardial infarction (MI). OBJECTIVE: To undertake a systematic
      review and meta-analysis of randomised placebo-controlled trials of oxygen
      therapy in MI. DATA SOURCES: Medline, Cochrane Database of Systematic Reviews,
      Cochrane Central Register of Controlled Trials, EMBASE and CINHAL. STUDY
      SELECTION: Randomised placebo-controlled trials of oxygen therapy in MI. DATA
      EXTRACTION: The primary clinical outcome was mortality. RESULTS: Two of 51
      potential studies met the inclusion criteria. The one study with substantive
      clinical outcome data reported that in uncomplicated MI, high-flow oxygen was
      associated with a non-significant increased risk of death (risk ratio 2.9, 95% CI
      0.8 to 10.3, p = 0.08) and a greater serum aspartate aminotransferase level
      (difference 19.2 IU/ml, 95% CI 0 to 38.4, p = 0.05) than room air. CONCLUSION:
      The limited evidence that does exist suggests that the routine use of high-flow
      oxygen in uncomplicated MI may result in a greater infarct size and possibly
      increase the risk of mortality.

PMID- 18708421
TI  - Limited utilities of N-terminal pro B-type natriuretic peptide and other newer
      risk markers compared with traditional risk factors for prediction of significant
      angiographic lesions in stable coronary artery disease.
AB  - OBJECTIVE: To investigate the usefulness of N-terminal pro-brain natriuretic
      peptide (NT-proBNP) as a predictive marker for angiographically significant
      coronary artery disease (CAD) and CAD severity compared with other newer
      biochemical risk markers and classic risk factors in patients with clinically
      suspected CAD. DESIGN: Cross-sectional evaluation of NT-proBNP in a large
      consecutive series of patients without a history of myocardial infarction
      referred for elective coronary angiography (CAG) between March 2004 and January
      2005. The value of NT-proBNP for predicting CAD was assessed and compared with
      high sensitivity C-reactive protein (hs-CRP), gamma-glutamyltransferase (GGT) and
      traditional risk factors. SETTING: Tertiary care centre, Department of
      Cardiology, Innsbruck Medical University, Austria. PATIENTS: 561 men and 287
      women aged between 20-86 years (median 65 years). INTERVENTIONS: None. MAIN
      OUTCOME MEASURES: Association of NT-proBNP with the severity of CAD, left
      ventricular dysfunction and comparison of predictive values of NT-proBNP, hs-CRP,
      GGT and traditional CAD risk factors. RESULTS: Of all tested newer biochemical
      risk markers NT-proBNP performed best. In a multinomial logistic regression model
      NT-proBNP but not hs-CRP or GGT was significantly associated with three-vessel
      CAD adjusted for age, sex, ventricular, renal function and classic risk factors
      (odds ratio = 1.667; 95% CI 1.003 to 2.772; p = 0.049). However, NT-proBNP had no
      additive predictive value to traditional cardiovascular risk factors for the
      prediction of angiographically significant CAD in a binary logistic regression
      model. CONCLUSIONS: The predictive value of NT-proBNP for CAD severity is better
      than that of hs-CRP or GGT. However, NT-proBNP is also of limited value compared
      with traditional risk factors for predicting significant CAD.

PMID- 18708422
TI  - The prevalence and the causes of minimal intestinal lesions in patients
      complaining of symptoms suggestive of enteropathy: a follow-up study.
AB  - AIMS: Although they are non-specific, minimal intestinal lesions are at the end
      of the coeliac histological damage spectrum. To investigate whether minimal
      intestinal lesions in patients without endomysial antibodies are due to coeliac
      disease, their prevalence, causes and risk of evolving into frank coeliac disease
      were studied. METHODS: From January 2000 to December 2005, 645 duodenal biopsies
      were performed. In 209 patients, duodenal biopsies were performed independently
      of endomysial antibody results. Clinical data and HLA-typing of all the patients
      negative to endomysial antibodies but with minimal mucosal lesions were re
      evaluated. Three years later, they were offered to be seen again, and further
      investigations were proposed. RESULTS: 14 out of 209 patients had minimal mucosal
      lesions and negative endomysial antibodies. Two patients were lost to follow-up;
      in 7/12 patients, symptoms and histological lesions were due to a different
      condition, not related to coeliac disease. In 11/12 patients, HLA-typing made
      diagnosis of coeliac disease very unlikely. Only one patient was on a gluten-free
      diet because of gluten-sensitive symptoms and was DQ2(+)/DQ8(+). CONCLUSIONS:
      Minimal duodenal lesions in patients negative to endomysial antibodies are rare
      and are likely to be due to conditions unrelated to coeliac disease.

PMID- 18708423
TI  - Gross pathology of the placenta: weight, shape, size, colour.
AB  - The gross examination is critical to making accurate diagnoses on placental
      specimens. An orderly evaluation of the cord, membranes and villous tissue allows
      maximal opportunity to recognise abnormalities. Many lesions have a pathognomonic
      gross appearance, while other processes are best seen on histology. Quantitation
      of the volume of placental tissue involved in an abnormal process is necessary to
      distinguish normal variation from significant pathology. Histological sections
      must include cord, membranes and central villous tissue.

PMID- 18708424
TI  - Revision 2: an immunohistochemical approach and evaluation of solid
      pseudopapillary tumour of the pancreas.
AB  - Solid pseudopapillary tumours (SPT) of the pancreas are uncommon, but with
      widespread and increased imaging, several of these lesions are coming to light
      incidentally and are subject to needle biopsies. On limited material and
      especially the solid or clear cell, variants of SPT can morphologically mimic
      most notably pancreatic neuroendocrine tumours and even metastatic renal cell
      carcinoma or melanoma. In this context, immunohistochemistry is important and
      useful in helping to reach the correct diagnosis. Several antibodies have been
      used in the immunohistochemical evaluation of SPT. As with most tumours, no one
      marker is specific, but rather a core panel is advocated. Recently, both beta
      catenin and E-cadherin have been shown to be of value in SPT. Nuclear and
      cytoplasmic decoration of tumour cells by beta-catenin is seen in almost 100% of
      cases. This protein relocalisation away from the cell membrane is underscored by
      mutations of the beta-catenin gene. Mutations of the CDH1 gene are very uncommon
      in SPT, but the immunohistochemically detected changes to the protein are
      consistent and present in 100% of cases. Using an E-cadherin antibody to the
      extracellular domain of the molecule results in complete membrane loss, while the
      antibody directed to the cytoplasmic fragment produces distinct nuclear staining
      of the tumour cells. In addition, there is concordance of staining abnormalities
      between the two antibodies. When combined with CD10 and progesterone receptor
      positivity, a diagnosis of SPT can be rendered with confidence even in small
      biopsy samples.

PMID- 18708425
TI  - A PCSK9 variant and familial combined hyperlipidaemia.
AB  - BACKGROUND: Our discovery in 2003 of the first mutations of PCSK9 gene causing
      autosomal dominant hypercholesterolaemia (ADH) shed light on an unknown factor
      that strongly influences the level of circulating low density lipoprotein
      cholesterol (LDL-C). PCSK9 gain of function mutations cause hypercholesterolaemia
      by a reduction of LDL receptor levels, while PCSK9 loss of function variants are
      associated with a reduction of LDL-C values and a decreased risk of coronary
      heart disease. METHODS AND RESULTS: We report an insertion of two leucines
      (p.L21tri also designated p.L15_L16ins2L) in the leucine stretch of the signal
      peptide of PCSK9 that is found in two of 25 families with familial combined
      hyperlipidaemia (FCHL). This mutant is associated with high total cholesterol and
      LDL-C values in these families and is found also in a patient with familial
      hypercholesterolaemia and her father. CONCLUSION: PCSK9 variants might contribute
      to FCHL phenotype and are to be taken into consideration in the study of this
      complex and multigenic disease with other genes implicated in dyslipidaemia.

PMID- 18708426
TI  - A novel mutation in the sulfate transporter gene SLC26A2 (DTDST) specific to the
      Finnish population causes de la Chapelle dysplasia.
AB  - BACKGROUND: Mutations in the sulfate transporter gene SLC26A2 (DTDST) cause a
      continuum of skeletal dysplasia phenotypes that includes achondrogenesis type 1B
      (ACG1B), atelosteogenesis type 2 (AO2), diastrophic dysplasia (DTD), and
      recessive multiple epiphyseal dysplasia (rMED). In 1972, de la Chapelle et al
      reported two siblings with a lethal skeletal dysplasia, which was denoted
      "neonatal osseous dysplasia" and "de la Chapelle dysplasia" (DLCD). It was
      suggested that DLCD might be part of the SLC26A2 spectrum of phenotypes, both
      because of the Finnish origin of the original family and of radiographic
      similarities to ACG1B and AO2. OBJECTIVE: To test the hypothesis whether SLC26A2
      mutations are responsible for DLCD. METHODS: We studied the DNA from the original
      DLCD family and from seven Finnish DTD patients in whom we had identified only
      one copy of IVS1+2T>C, the common Finnish mutation. A novel SLC26A2 mutation was
      found in all subjects, inserted by site-directed mutagenesis in a vector
      harbouring the SLC26A2 cDNA, and expressed in sulfate transport deficient Chinese
      hamster ovary (CHO) cells to measure sulfate uptake activity. RESULTS: We
      identified a hitherto undescribed SLC26A2 mutation, T512K, homozygous in the
      affected subjects and heterozygous in both parents and in the unaffected sister.
      T512K was then identified as second pathogenic allele in the seven Finnish DTD
      subjects. Expression studies confirmed pathogenicity. CONCLUSIONS: DLCD is indeed
      allelic to the other SLC26A2 disorders. T512K is a second rare "Finnish" mutation
      that results in DLCD at homozygosity and in DTD when compounded with the milder,
      common Finnish mutation.

PMID- 18708427
TI  - Reversible phenotype in a mouse model of Hutchinson-Gilford progeria syndrome.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare progeroid syndrome caused
      by mutations in the LMNA gene. Currently there is no treatment available for
      HGPS, but promising results from several studies using farnesyl transferase
      inhibitors (FTIs) on cells and animal models of HGPS have been published and a
      clinical trial using FTIs has been started in patients with HGPS. However, the
      published data from animal models treated with FTIs come from studies where the
      treatment was started before pronounced disease development. This study used an
      inducible transgenic animal model of HGPS with abnormalities of the skin and
      teeth. After phenotype development, the transgenic expression was turned off and
      a rapid improvement of the phenotype was noted, within 4 weeks of transgenic
      suppression. After 13 weeks, the skin was almost indistinguishable from wild-type
      skin. This study shows that in these tissues, expression of the progeria mutation
      does not cause irreversible damage and that reversal of disease phenotype is
      possible, which gives promise for a treatment for this disease.

PMID- 18708428
TI  - Local accountability in the NHS.

PMID- 18708429
TI  - Gestational trophoblastic disease: current management of hydatidiform mole.

PMID- 18708430
TI  - Surgeons' tap use plays a key part in reducing water waste.

PMID- 18708431
TI  - Quebec board denied list of patients with cardiac devices.

PMID- 18708432
TI  - Bulgarian minister resigns after bone marrow transplant investigation.

PMID- 18708433
TI  - Antibiotics account for 19% of emergency department visits in US for adverse
      events.

PMID- 18708434
TI  - Clinical use of cabergoline as primary and adjunctive treatment for acromegaly.
AB  - BACKGROUND: Cabergoline is a dopamine agonist that may be used as primary or
      adjunctive therapy for acromegaly. Although one study suggested biochemical
      control may be achieved in a substantial proportion of patients, it is still
      commonly perceived to be a relatively ineffective treatment. DESIGN AND METHOD: A
      prospective audit was performed of 15 consecutive acromegalic patients (eight
      males, seven females, median age 55, range 31-92 at presentation) treated with
      cabergoline to determine the effective dose and tolerability. All had normal
      anterior pituitary function; two patients had hyperprolactinaemia. Magnetic
      resonance imaging revealed nine adenomata, two partially empty sellae and four
      structurally normal pituitary glands. Nine patients had undergone transsphenoidal
      surgery 1-12 months, and one patient had received pituitary radiotherapy 18
      years, prior to commencement of cabergoline. All patients had biochemical GH
      excess; median serum IGF1 471 ng/ml, range 239-746 ng/ml. The calculated mean of
      a series of GH measurements ranged from 2.7-45.8 mIU/l, median 9.7 mIU/l.
      RESULTS: On a median weekly dose of cabergoline of 1.75 mg (range 0.5-7 mg)
      normalisation of both IGF1 and GH occurred in 4 out of the 15 patients (27%). Out
      of the 15 patients (33%), 5 achieved a serum IGF1 within the reference range with
      notable reductions seen in a further five patients. Nine patients (60%) achieved
      a mean serum GH level of less than 5 mIU/l. Duration of treatment was 2-52 months
      and was well tolerated in 14 patients. CONCLUSION: Cabergoline can be an
      effective and well tolerated primary or adjunctive therapy for acromegaly and
      useful clinical responses are noted even with modest doses.

PMID- 18708435
TI  - Rituximab in Graves' disease.

PMID- 18708436
TI  - Follow-up of pituitary tumor volume in patients with acromegaly treated with
      pegvisomant in clinical trials.
AB  - OBJECTIVE: We examined pituitary tumor volumes in patients treated with
      pegvisomant for 18 months or longer, and in whom the tumors were monitored for at
      least 3 years. We present details on 9 of 304 patients in clinical trials with
      pegvisomant who experienced tumor growth within the first year of treatment.
      METHOD: Magnetic resonance images prior to start of pegvisomant and at last
      follow-up were examined in 43 patients (14% of participating patients). Twenty
      nine had received prior radiation therapy (18% of irradiated patients) and all
      but five received somatostatin analogs between periods of pegvisomant treatment.
      RESULTS: At follow-up, the median tumor volume was 0.6 cc (range 0.0-19.7 cc), in
      comparison with 1.6 cc (0.0-19.7 cc) at baseline (P<0.001). Twenty-five patients,
      of which 23 received radiation therapy, had tumor volume reduction. Seventeen
      patients had no significant change. One patient, who had not received radiation
      therapy, had an increase in tumor volume from 1.61 to 1.93 cc. Of the nine
      patients with tumor growth, six had progressive growth before initiating
      pegvisomant. Two patients with stable tumors while on octreotide experienced
      enlargement after octreotide discontinuation but remained stable on long-term
      pegvisomant therapy. CONCLUSION: The present data indicate that pegvisomant does
      not promote tumor growth and suggest that the nine observed cases of tumor
      progression, which occurred within 8 months after commencing pegvisomant, are
      likely rebound expansions after discontinuation of somatostatin analogs and/or
      the natural history of aggressively growing pituitary tumors. Continued long-term
      surveillance of tumor volume, particularly in non-irradiated patients, is
      recommended.

PMID- 18708437
TI  - Sex steroids in androgen-secreting adrenocortical tumors: clinical and hormonal
      features in comparison with non-tumoral causes of androgen excess.
AB  - OBJECTIVE: Adrenocortical tumors (ACT) account for no more than 0.2% of the
      causes of androgen excess (AE). Conversely, these rare tumors have a very poor
      prognosis. It is difficult and important to exclude this diagnosis whenever there
      is AE. DESIGN: Retrospective investigation of androgen profiles in a large
      consecutive series of androgen-secreting (AS) ACT to assess their relative
      diagnostic value. METHODS: A total of 44 consecutive female patients with ACT-AS
      and a comparison group of 102 women with non-tumor causes of AE (NTAE). RESULTS:
      Patients with ACT-AS were older than the ones with NTAE (37.7 vs 24.8 years;
      P<0.001) and the prevalence of hirsutism, acne, and oligo/amenorrhea were not
      different. Free testosterone was the most commonly elevated androgen in ACT-AS
      (94%), followed by androstenedione (90%), DHEAS (82%), and total testosterone
      (76%), and all three androgens were simultaneously elevated in 56% of the cases.
      Androgen serum levels became subnormal in all ACT-AS patients after complete
      tumor removal. In NTAE, the most commonly elevated androgen was androstenedione
      (93%), while all three androgens were elevated in only 22% of the cases. Free
      testosterone values above 6.85 pg/ml (23.6 pmol/l) had the best diagnostic value
      for ACT-AS (sensitivity 82%, confidence interval (CI): 57-96%; specificity 97%,
      CI: 91-100%). Basal LH and FSH levels were significantly lower in the ACT-AS
      group. CONCLUSION: Free testosterone was the most reliable marker of ACT-AS.
      However, the large overlap of androgen levels between ACT-AS and NTAE groups
      suggests that additional hormonal and/or imaging investigations are required to
      rule out ACT-AS in case of increased androgens.

PMID- 18708438
TI  - Morphological and biochemical characterization of basal and starvation-induced
      autophagy in isolated adult rat cardiomyocytes.
AB  - Autophagy is simultaneously a mode of programmed cell death and an important
      physiological process for cell survival, but its pathophysiological significance
      in cardiac myocytes remains largely unknown. We induced autophagy in isolated
      adult rat ventricular cardiomyocytes (ARVCs) by incubating them in glucose-free,
      mannitol-supplemented medium for up to 4 days. Ultrastructurally, intracellular
      vacuoles containing degenerated subcellular organelles (e.g., mitochondria) were
      markedly apparent in the glucose-starved cells. Microtubule-associated protein-1
      light chain 3 was significantly upregulated among the glucose-starved ARVCs than
      among the controls. After 4 days, glucose-starved ARVCs showed a significantly
      worse survival rate (19+/-5.2%) than the controls (55+/-8.3%, P<0.005). Most dead
      ARVCs in both groups showed features of necrosis, and the rate of apoptosis did
      not differ between the groups. Two inhibitors of autophagy, 3-methyladenine (3
      MA) and leupeptin, significantly and dose-dependently reduced the viability of
      both control and glucose-starved ARVCs and caused specific morphological
      alterations; 3-MA reduced autophagic findings, whereas leupeptin greatly
      increased the numbers and the sizes of vacuoles that contained incompletely
      digested organelles. The knockdown of the autophagy-related genes with small
      interfering RNA also reduced the glucose-starved ARVCs viability, but rapamycin,
      an autophagy enhancer, improved it. Reductions in the ATP content of ARVCs caused
      by glucose depletion were exacerbated by the inhibitors while attenuated by
      rapamycin, suggesting that autophagy inhibition might accelerate energy
      depletion, leading to necrosis. Taken together, our findings suggest that
      autophagy in cardiomyocytes reflects a prosurvival, compensatory response to
      stress and that autophagic cardiomyocyte death represents an unsuccessful outcome
      due to necrosis.

PMID- 18708439
TI  - Proteasome inhibition in hypertrophied myocardium.

PMID- 18708440
TI  - To oxygenate or not to oxygenate--that is the question.

PMID- 18708441
TI  - Polarity reversal lowers activation time during diastolic field stimulation of
      the rabbit ventricles: insights into mechanisms.
AB  - To fully characterize the mechanisms of defibrillation, it is necessary to
      understand the response, within the three-dimensional (3D) volume of the
      ventricles, to shocks given in diastole. Studies that have examined diastolic
      responses conducted measurements on the epicardium or on a transmural surface of
      the left ventricular (LV) wall only. The goal of this study was to use optical
      imaging experiments and 3D bidomain simulations, including a model of optical
      mapping, to ascertain the shock-induced virtual electrode and activation patterns
      throughout the rabbit ventricles following diastolic shocks. We tested the
      hypothesis that the locations of shock-induced regions of hyperpolarization
      govern the different diastolic activation patterns for shocks of reversed
      polarity. In model and experiment, uniform-field monophasic shocks of reversed
      polarities (cathode over the right ventricle is RV-, reverse polarity is LV-)
      were applied to the ventricles in diastole. Experiments and simulations revealed
      that RV- shocks resulted in longer activation times compared with LV- shocks of
      the same strength. 3D simulations demonstrated that RV- shocks induced a greater
      volume of hyperpolarization at shock end compared with LV- shocks; most of these
      hyperpolarized regions were located in the LV. The results of this study indicate
      that ventricular geometry plays an important role in both the location and size
      of the shock-induced virtual anodes that determine activation delay during the
      shock and subsequently affect shock-induced propagation. If regions of
      hyperpolarization that develop during the shock are sufficiently large,
      activation delay may persist until shock end.

PMID- 18708442
TI  - Regulating RISK: a role for JAK-STAT signaling in postconditioning?
AB  - Postconditioning (POC), a novel strategy of cardioprotection against ischemia
      reperfusion injury, is clinically attractive because of its therapeutic
      application at the predictable onset of reperfusion. POC activates several
      intracellular kinase signaling pathways, including phosphatidylinositol 3-kinase
      (PI3K)-Akt (RISK). The regulation of POC-induced survival kinase signaling,
      however, has not been fully characterized. JAK-STAT activation is integral to
      cardiac ischemic tolerance and may provide upstream regulation of RISK. We
      hypothesized that POC requires the activation of both JAK-STAT and RISK
      signaling. Langendorff-perfused mouse hearts were subjected to 30 min of global
      ischemia and 40 min of reperfusion, with or without POC immediately after
      ischemia. A separate group of POC hearts was treated with AG 490, a JAK2
      inhibitor, Stattic, a specific STAT3 inhibitor, or LY-294002, a PI3K inhibitor,
      at the onset of reperfusion. Cardiomyocyte-specific STAT3 knockout (KO) hearts
      were also subjected to non-POC or POC protocols. Myocardial performance
      (+dP/dt(max), mmHg/s) was assessed throughout each perfusion protocol.
      Phosphorylated (p-) STAT3 and Akt expression was analyzed by Western
      immunoblotting. POC enhanced myocardial functional recovery and increased
      expression of p-STAT3 and p-Akt. JAK-STAT inhibition abrogated POC-induced
      functional protection. STAT3 inhibition decreased expression of both p-STAT3 and
      p-Akt. PI3K inhibition also attenuated POC-induced cardioprotection and reduced p
      Akt expression but had no effect on STAT3 phosphorylation. Interestingly, STAT3
      KO hearts undergoing POC exhibited improved ischemic tolerance compared with KO
      non-POC hearts. POC induces myocardial functional protection by activating the
      RISK pathway. JAK-STAT signaling, however, is insufficient for effective POC
      without PI3K-Akt activation.

PMID- 18708443
TI  - The impact of baseline diameter on flow-mediated dilation differs in young and
      older humans.
AB  - Flow-mediated dilation (FMD) has become a commonly applied approach for the
      assessment of vascular function and health, but methods used to calculate FMD
      differ between studies. For example, the baseline diameter used as a benchmark is
      sometimes assessed before cuff inflation, whereas others use the diameter during
      cuff inflation. Therefore, we compared the brachial artery diameter before and
      during cuff inflation and calculated the resulting FMD in healthy children (n=45;
      10+/-1 yr), adults (n=31; 28+/-6 yr), and older subjects (n=22; 58+/-5 yr).
      Brachial artery FMD was examined after 5 min of distal ischemia. Diameter was
      determined from either 30 s before cuff inflation or from the last 30 s during
      cuff inflation. Edge detection and wall tracking of high resolution B-mode
      arterial ultrasound images was used to calculate conduit artery diameter.
      Brachial artery diameter during cuff inflation was significantly larger than
      before inflation in children (P=0.02) and adults (P<0.001) but not in older
      subjects (P=0.59). Accordingly, FMD values significantly differed in children
      (11.2+/-5.1% vs. 9.4+/-5.2%; P=0.02) and adults (7.3+/-3.2% vs. 4.6+/-3.3%;
      P<0.001) but not in older subjects (6.3+/-3.4% vs. 6.0+/-4.2%; P=0.77). When the
      diameter before cuff inflation was used, an age-dependent decline was evident in
      FMD, whereas FMD calculated using the diameter during inflation was associated
      with higher FMD values in older than younger adults. In summary, the inflation of
      the cuff significantly increases brachial artery diameter, which results in a
      lower FMD response. This effect was found to be age dependent, which emphasizes
      the importance of using appropriate methodology to calculate the FMD.

PMID- 18708445
TI  - Venous response to orthostatic stress.
AB  - Head-up tilt (HUT) induces a reduction in preload, which is thought to be
      restored through sympathetic venoconstriction, reducing unstressed volume (V(u))
      and venous compliance (VeC). In this study, we assessed venous inflow and outflow
      responses and their reproducibility and determined the relation with autonomic
      function during HUT. Eight healthy non-pregnant women were subjected to 20
      degrees head-down tilt to 60 degrees HUT at 20 degrees intervals. At each
      rotational step, we randomly assessed forearm pressure-volume (P-V) curves
      (venous occlusion plethysmography) during inflow (VeC(IN)) and outflow [venous
      emptying rate (VER(OUT))]. VeC(IN) was defined as the ratio of the slope of the
      volume-time curve and pressure-time curve, with direct intravenous pressure
      measurement. VER(OUT) was determined using the derivate of a quadratic regression
      model using cuff pressure. We defined V(u) as the y-intercept of the P-V curve.
      We calculated, for both methods, the coefficients of reproducibility (CR) and
      variation (CV). Vascular sympathetic activity was determined by spectral
      analysis. VeC(IN) decreased at each rotational step compared with the supine
      position (P<0.05), whereas VER(OUT) increased. CR of VeC(IN) was higher in the
      supine position than VER(OUT) but lower during HUT. CV varied between 19% and 25%
      (VeC(IN)) and between 12% and 21% (VER(OUT)). HUT decreased V(u). The change in
      VeC(IN) and VER(OUT) correlated with the change in vascular sympathetic activity
      (r= -0.36, P<0.01, and r=0.48, P<0.01). This is the first study in which a
      reproducible reduction in VeC(IN) and V(u) and a rise in VER(OUT) during HUT are
      documented. The alterations in venous characteristics relate to changes in
      vascular sympathetic activity.

PMID- 18708444
TI  - Internalization of eNOS via caveolae regulates PAF-induced inflammatory
      hyperpermeability to macromolecules.
AB  - Endothelial nitric oxide (NO) synthase (eNOS) is thought to regulate
      microvascular permeability via NO production. We tested the hypotheses that the
      expression of eNOS and eNOS endocytosis by caveolae are fundamental for
      appropriate signaling mechanisms in inflammatory endothelial permeability to
      macromolecules. We used bovine coronary postcapillary venular endothelial cells
      (CVECs) because these cells are derived from the microvascular segment
      responsible for the transport of macromolecules in inflammation. We stimulated
      CVECs with platelet-activating factor (PAF) at 100 nM and measured eNOS
      phosphorylation, NO production, and CVEC monolayer permeability to FITC-dextran
      70 KDa (Dx-70). PAF translocated eNOS from plasma membrane to cytosol, induced
      changes in the phosphorylation state of the enzyme, and increased NO production
      from 4.3+/-3.8 to 467+/-22.6 nM. PAF elevated CVEC monolayer permeability to FITC
      Dx-70 from 3.4+/-0.3 x 10(-6) to 8.5+/-0.4 x 10(-6) cm/s. The depletion of
      endogenous eNOS with small interfering RNA abolished PAF-induced
      hyperpermeability, demonstrating that the expression of eNOS is required for
      inflammatory hyperpermeability responses. The inhibition of the caveolar
      internalization by blocking caveolar scission using transfection of dynamin
      dominant-negative mutant, dyn2K44A, inhibited PAF-induced hyperpermeability to
      FITC-Dx-70. We interpret these data as evidence that 1) eNOS is required for
      hyperpermeability to macromolecules and 2) the internalization of eNOS via
      caveolae is an important mechanism in the regulation of endothelial permeability.
      We advance the novel concept that eNOS internalization to cytosol is a signaling
      mechanism for the onset of microvascular hyperpermeability in inflammation.

PMID- 18708446
TI  - Regulation of cardiac myocyte contractility by phospholemman: Na+/Ca2+ exchange
      versus Na+ -K+ -ATPase.
AB  - Phospholemman (PLM) regulates cardiac Na(+)/Ca(2+) exchanger (NCX1) and Na(+)
      K(+)-ATPase in cardiac myocytes. PLM, when phosphorylated at Ser(68), disinhibits
      Na(+)-K(+)-ATPase but inhibits NCX1. PLM regulates cardiac contractility by
      modulating Na(+)-K(+)-ATPase and/or NCX1. In this study, we first demonstrated
      that adult mouse cardiac myocytes cultured for 48 h had normal surface membrane
      areas, t-tubules, and NCX1 and sarco(endo)plasmic reticulum Ca(2+)-ATPase levels,
      and retained near normal contractility, but alpha(1)-subunit of Na(+)-K(+)-ATPase
      was slightly decreased. Differences in contractility between myocytes isolated
      from wild-type (WT) and PLM knockout (KO) hearts were preserved after 48 h of
      culture. Infection with adenovirus expressing green fluorescent protein (GFP) did
      not affect contractility at 48 h. When WT PLM was overexpressed in PLM KO
      myocytes, contractility and cytosolic Ca(2+) concentration ([Ca(2+)](i))
      transients reverted back to those observed in cultured WT myocytes. Both Na(+)
      K(+)-ATPase current (I(pump)) and Na(+)/Ca(2+) exchange current (I(NaCa)) in PLM
      KO myocytes rescued with WT PLM were depressed compared with PLM KO myocytes.
      Overexpressing the PLMS68E mutant (phosphomimetic) in PLM KO myocytes resulted in
      the suppression of I(NaCa) but had no effect on I(pump). Contractility,
      [Ca(2+)](i) transient amplitudes, and sarcoplasmic reticulum Ca(2+) contents in
      PLM KO myocytes overexpressing the PLMS68E mutant were depressed compared with
      PLM KO myocytes overexpressing GFP. Overexpressing the PLMS68A mutant (mimicking
      unphosphorylated PLM) in PLM KO myocytes had no effect on I(NaCa) but decreased
      I(pump). Contractility, [Ca(2+)](i) transient amplitudes, and sarcoplasmic
      reticulum Ca(2+) contents in PLM KO myocytes overexpressing the S68A mutant were
      similar to PLM KO myocytes overexpressing GFP. We conclude that at the single
      myocyte level, PLM affects cardiac contractility and [Ca(2+)](i) homeostasis
      primarily by its direct inhibitory effects on Na(+)/Ca(2+) exchange.

PMID- 18708449
TI  - John Bryant takes a closer look at some of this month's Original Articles.

PMID- 18708447
TI  - Hypertension and disrupted blood pressure circadian rhythm in type 2 diabetic
      db/db mice.
AB  - Human Type 2 diabetes is associated with increased incidence of hypertension and
      disrupted blood pressure (BP) circadian rhythm. Db/db mice have been used
      extensively as a model of Type 2 diabetes, but their BP is not well
      characterized. In this study, we used radiotelemetry to define BP and the
      circadian rhythm in db/db mice. We found that the systolic, diastolic, and mean
      arterial pressures were each significantly increased by 11, 8, and 9 mmHg in
      db/db mice compared with controls. In contrast, no difference was observed in
      pulse pressure or heart rate. Interestingly, both the length of time db/db mice
      were active (locomotor) and the intensity of locomotor activity were
      significantly decreased in db/db mice. In contrast to controls, the 12-h light
      period average BP in db/db mice did not dip significantly from the 12-h dark
      period. A partial Fourier analysis of the continuous 72-h BP data revealed that
      the power and the amplitude of the 24-h period length rhythm were significantly
      decreased in db/db mice compared with the controls. The acrophase was centered at
      0141 in control mice, but became scattered from 1805 to 0236 in db/db mice. In
      addition to BP, the circadian rhythms of heart rate and locomotor activity were
      also disrupted in db/db mice. The mean arterial pressure during the light period
      correlates with plasma glucose, insulin, and body weight. Moreover, the
      oscillations of the clock genes DBP and Bmal1 but not Per1 were significantly
      dampened in db/db mouse aorta compared with controls. In summary, our data show
      that db/db mice are hypertensive with a disrupted BP, heart rate, and locomotor
      circadian rhythm. Such changes are associated with dampened oscillations of clock
      genes DBP and Bmal1 in vasculature.

PMID- 18708450
TI  - Growing actin networks form lamellipodium and lamellum by self-assembly.
AB  - Many different cell types are able to migrate by formation of a thin actin-based
      cytoskeletal extension. Recently, it became evident that this extension consists
      of two distinct substructures, designated lamellipodium and lamellum, which
      differ significantly in their kinetic and kinematic properties as well as their
      biochemical composition. We developed a stochastic two-dimensional computer
      simulation that includes chemical reaction kinetics, G-actin diffusion, and
      filament transport to investigate the formation of growing actin networks in
      migrating cells. Model parameters were chosen based on experimental data or
      theoretical considerations. In this work, we demonstrate the system's ability to
      form two distinct networks by self-organization. We found a characteristic
      transition in mean filament length as well as a distinct maximum in
      depolymerization flux, both within the first 1-2 microm. The separation into two
      distinct substructures was found to be extremely robust with respect to initial
      conditions and variation of model parameters. We quantitatively investigated the
      complex interplay between ADF/cofilin and tropomyosin and propose a plausible
      mechanism that leads to spatial separation of, respectively, ADF/cofilin- or
      tropomyosin-dominated compartments. Tropomyosin was found to play an important
      role in stabilizing the lamellar actin network. Furthermore, the influence of
      filament severing and annealing on the network properties is explored, and
      simulation data are compared to existing experimental data.

PMID- 18708451
TI  - New proposed mechanism of actin-polymerization-driven motility.
AB  - We present the first numerical simulation of actin-driven propulsion by elastic
      filaments. Specifically, we use a Brownian dynamics formulation of the dendritic
      nucleation model of actin-driven propulsion. We show that the model leads to a
      self-assembled network that exerts forces on a disk and pushes it with an average
      speed. This simulation approach is the first to observe a speed that varies
      nonmonotonically with the concentration of branching proteins (Arp2/3), capping
      protein, and depolymerization rate, in accord with experimental observations. Our
      results suggest a new interpretation of the origin of motility. When we estimate
      the speed that this mechanism would produce in a system with realistic rate
      constants and concentrations as well as fluid flow, we obtain a value that is
      within an order-of-magnitude of the polymerization speed deduced from
      experiments.

PMID- 18708452
TI  - Models of toxic beta-sheet channels of protegrin-1 suggest a common subunit
      organization motif shared with toxic alzheimer beta-amyloid ion channels.
AB  - Antimicrobial peptides (AMPs) induce cytotoxicity by altering membrane
      permeability. The electrical properties of membrane-associated AMPs as well as
      their cellular effects have been extensively documented; however their three
      dimensional structure is poorly understood. Gaining insight into channel
      structures is important to the understanding of the protegrin-1 (PG-1) and other
      AMP cytolytic mechanisms, and to antibiotics design. We studied the beta-sheet
      channels morphology using molecular dynamics simulations. We modeled PG-1
      channels as intrinsic barrel-stave and toroidal membrane pores, and simulated
      them in zwitterionic and anionic lipid bilayers. PG-1 channels consist of eight
      beta-hairpins in a consecutive NCCN (N and C represent the beta-hairpin's N- and
      C-termini) packing organization yielding antiparallel and parallel beta-sheet
      channels. Both channels preserve the toroidal, but not the barrel-stave pores.
      The two lipid leaflets of the bilayer bend toward each other at the channels'
      edges, producing a semitoroidal pore with the outward-pointing hydrophobic
      residues preventing the polar lipid headgroups from moving to the bilayer center.
      In all simulated lipid environments, PG-1 channels divide into four or five beta
      sheet subunits consisting of single or dimeric beta-hairpins. The channel
      morphology with subunit organization is consistent with the four to five subunits
      observed by NMR in the POPE/POPG bilayer. Remarkably, a beta-sheet subunit
      channel motif is in agreement with Alzheimer ion channels modeled using the
      universal U-shape beta-strand-turn-beta-strand structure, as well as with high
      resolution atomic force microscopy images of beta-amyloid channels with four to
      six subunits. Consistent with the toxic beta-amyloid channels that are ion
      conducting, the PG-1 channels permeate anions.

PMID- 18708453
TI  - Structure of SP-B/DPPC mixed films studied by neutron reflectometry.
AB  - The structures of films of pulmonary surfactant protein B (SP-B) and mixtures of
      SP-B and dipalmitoylphosphatidylcholine (DPPC) at the air/water interface have
      been studied by neutron reflectometry and Langmuir film balance methods. From the
      film balance studies, we observe that the isotherms of pure DPPC and SP-B/DPPC
      mixtures very nearly overlay one another at very high pressures, suggesting that
      the SP-B is being excluded from the film. The use of multiple contrasts with
      neutron reflectometry at a range of surface pressures has enabled the mixing and
      squeeze out of the DPPC and SP-B mixtures to be studied. We can identify the SP-B
      component of the interfacial structure and its position as a function of surface
      pressure. The mixtures are initially a homogeneous layer at low surface
      pressures. At higher surface pressures, the SP-B is squeezed out of the lipid
      layer into the subphase, with the first signs detected at 30 mN m(-1). At 50 mN
      m(-1), the subphase is almost completely excluded from the DPPC layer, with the
      SP-B content significantly reduced. Only a small amount of DPPC appears to be
      associated with the squeezed out SP-B.

PMID- 18708454
TI  - Measurement of two-dimensional binding constants between cell-bound major
      histocompatibility complex and immobilized antibodies with an acoustic biosensor.
AB  - Gaining insights into the dynamic processes of molecular interactions that
      mediate cell-substrate and cell-cell adhesion is of great significance in the
      understanding of numerous physiological processes driven by intercellular
      communication. Here, an acoustic-wave biosensor is used to study and characterize
      specific interactions between cell-bound membrane proteins and surface
      immobilized ligands, using as a model system the binding of major
      histocompatibility complex class I HLA-A2 proteins to anti-HLA-A2 monoclonal
      antibodies. The energy of the acoustic signal, measured as amplitude change, was
      found to depend directly on the number of HLA-A2/antibody complexes formed on the
      device surface. Real-time acoustic data were used to monitor the surface binding
      of cell suspensions at a range of 6.0 x 10(4) to 6.0 x 10(5) cells mL(-1).
      Membrane interactions are governed by two-dimensional chemistry because of the
      molecules' confinement to the lipid bilayer. The two-dimensional kinetics and
      affinity constant of the HLA-A2/antibody interaction were calculated (k(a) = 1.15
      x 10(-5) mum(2) s(-1) per molecule, k(d) = 2.07 x 10(-5) s(-1), and K(A) = 0.556
      mum(2) per molecule, at 25 degrees C), based on a detailed acoustic data
      analysis. Results indicate that acoustic biosensors can emerge as a significant
      tool for probing and characterizing cell-membrane interactions in the immune
      system, and for fast and label-free screening of membrane molecules using whole
      cells.

PMID- 18708455
TI  - Anion-cation permeability correlates with hydrated counterion size in glycine
      receptor channels.
AB  - The functional role of ligand-gated ion channels depends critically on whether
      they are predominantly permeable to cations or anions. However, these, and other
      ion channels, are not perfectly selective, allowing some counterions to also
      permeate. To address the mechanisms by which such counterion permeation occurs,
      we measured the anion-cation permeabilities of different alkali cations, Li(+)
      Na(+), and Cs(+), relative to either Cl(-) or NO(3)(-) anions in both a wild-type
      glycine receptor channel (GlyR) and a mutant GlyR with a wider pore diameter. We
      hypothesized and showed that counterion permeation in anionic channels correlated
      inversely with an equivalent or effective hydrated size of the cation relative to
      the channel pore radius, with larger counterion permeabilities being observed in
      the wider pore channel. We also showed that the anion component of conductance
      was independent of the nature of the cation. We suggest that anions and
      counterion cations can permeate through the pore as neutral ion pairs, to allow
      the cations to overcome the large energy barriers resulting from the positively
      charged selectivity filter in small GlyR channels, with the permeability of such
      ion pairs being dependent on the effective hydrated diameter of the ion pair
      relative to the pore diameter.

PMID- 18708456
TI  - FCS study of the thermodynamics of membrane protein insertion into the lipid
      bilayer chaperoned by fluorinated surfactants.
AB  - Experimental determination of the free energy (DeltaG) stabilizing the structure
      of membrane proteins (MPs) in their native environment has been hampered by the
      aggregation and precipitation of MPs outside the lipid bilayer. We recently
      demonstrated that the latter process can be prevented by the use of fluorinated
      surfactants, FTACs, that act as chaperones for MP insertion without partitioning
      in the membrane themselves. Here we combine the advantages of the chaperone-like
      ability of FTACs with the sensitivity of fluorescence correlation spectroscopy
      measurements to determine DeltaG of bilayer insertion of model MPs. First, we
      calibrate our approach by examining the effects of chaperoned insertion on DeltaG
      of transmembrane insertion of Annexin B12. We find that a shorter-chained
      surfactant, FTAC-C6, for which the working concentration range of 0.05-0.2 mM
      falls below CMC = 0.33 mM, has a mild effect on an apparent DeltaG. In contrast,
      additions of a longer-chained FTAC-C8 (CMC = 0.03 mM) result in a steep and
      nonlinear concentration dependence of DeltaG. We then apply the same methodology
      to the pH-triggered insertion of diphtheria toxin T-domain, which is known to be
      affected by nonproductive aggregation in solution. We find that the correction of
      the DeltaG value needed to compensate for unchaperoned insertion of the T-domain
      exceeds 3 kcal/mole. A relatively shallow and linear dependence of the DeltaG for
      Annexin B12 and T-domain insertion on FTAC-C6 concentration is encouraging for
      future applications of this surfactant in thermodynamic studies of the stability
      of other MPs.

PMID- 18708457
TI  - Molecular mechanism of ion-ion and ion-substrate coupling in the Na+-dependent
      leucine transporter LeuT.
AB  - Ion-coupled transport of neurotransmitter molecules by neurotransmitter:sodium
      symporters (NSS) play an important role in the regulation of neuronal signaling.
      One of the major events in the transport cycle is ion-substrate coupling and
      formation of the high-affinity occluded state with bound ions and substrate.
      Molecular mechanisms of ion-substrate coupling and the corresponding ion
      substrate stoichiometry in NSS transporters has yet to be understood. The recent
      determination of a high-resolution structure for a bacterial homolog of Na(+)/Cl(
      )-dependent neurotransmitter transporters, LeuT, offers a unique opportunity to
      analyze the functional roles of the multi-ion binding sites within the binding
      pocket. The binding pocket of LeuT contains two metal binding sites. The first
      ion in site NA1 is directly coupled to the bound substrate (Leu) with the second
      ion in the neighboring site (NA2) only approximately 7 A away. Extensive, fully
      atomistic, molecular dynamics, and free energy simulations of LeuT in an explicit
      lipid bilayer are performed to evaluate substrate-binding affinity as a function
      of the ion load (single versus double occupancy) and occupancy by specific
      monovalent cations. It was shown that double ion occupancy of the binding pocket
      is required to ensure substrate coupling to Na(+) and not to Li(+) or K(+)
      cations. Furthermore, it was found that presence of the ion in site NA2 is
      required for structural stability of the binding pocket as well as amplified
      selectivity for Na(+) in the case of double ion occupancy.

PMID- 18708458
TI  - Hydrogen bond switching among flavin and amino acid side chains in the BLUF
      photoreceptor observed by ultrafast infrared spectroscopy.
AB  - BLUF domains constitute a recently discovered class of photoreceptor proteins
      found in bacteria and eukaryotic algae. BLUF domains are blue-light sensitive
      through a FAD cofactor that is involved in an extensive hydrogen-bond network
      with nearby amino acid side chains, including a highly conserved tyrosine and
      glutamine. The participation of particular amino acid side chains in the
      ultrafast hydrogen-bond switching reaction with FAD that underlies
      photoactivation of BLUF domains is assessed by means of ultrafast infrared
      spectroscopy. Blue-light absorption by FAD results in formation of FAD(*-) and a
      bleach of the tyrosine ring vibrational mode on a picosecond timescale, showing
      that electron transfer from tyrosine to FAD constitutes the primary
      photochemistry. This interpretation is supported by the absence of a kinetic
      isotope effect on the fluorescence decay on H/D exchange. Subsequent protonation
      of FAD(*-) to result in FADH(*) on a picosecond timescale is evidenced by the
      appearance of a N-H bending mode at the FAD N5 protonation site and of a FADH(*)
      C=N stretch marker mode, with tyrosine as the likely proton donor. FADH(*) is
      reoxidized in 67 ps (180 ps in D(2)O) to result in a long-lived hydrogen-bond
      switched network around FAD. This hydrogen-bond switch shows infrared signatures
      from the C-OH stretch of tyrosine and the FAD C4=O and C=N stretches, which
      indicate increased hydrogen-bond strength at all these sites. The results support
      a previously hypothesized rotation of glutamine by approximately 180 degrees
      through a light-driven radical-pair mechanism as the determinant of the hydrogen
      bond switch.

PMID- 18708459
TI  - The activity of the amphipathic peptide delta-lysin correlates with phospholipid
      acyl chain structure and bilayer elastic properties.
AB  - Release of lipid vesicle content induced by the amphipathic peptide delta-lysin
      was investigated as a function of lipid acyl chain length and degree of
      unsaturation for a series of phosphatidylcholines. Dye efflux and peptide binding
      were examined for three homologous lipid series: di-monounsaturated, di
      polyunsaturated, and asymmetric phosphatidylcholines, with one saturated and one
      monounsaturated acyl chain. Except for the third series, peptide activity
      correlated with the first moment of the lateral pressure profile, which is a
      function of lipid acyl chain structure. In vesicles composed of asymmetric
      phosphatidylcholines, peptide binding and dye efflux are enhanced compared to
      symmetric, unsaturated lipids with similar pressure profiles. We attribute this
      to the entropically more favorable interaction of delta-lysin with partially
      saturated phospholipids. We find that lipid acyl chain structure has a major
      impact on the activity of delta-lysin and is likely to be an important factor
      contributing to the target specificity of amphipathic peptides.

PMID- 18708460
TI  - DEND mutation in Kir6.2 (KCNJ11) reveals a flexible N-terminal region critical
      for ATP-sensing of the KATP channel.
AB  - ATP-sensitive K(+)-channels link metabolism and excitability in neurons,
      myocytes, and pancreatic islets. Mutations in the pore-forming subunit (Kir6.2;
      KCNJ11) cause neonatal diabetes, developmental delay, and epilepsy by decreasing
      sensitivity to ATP inhibition and suppressing electrical activity. Mutations of
      residue G53 underlie both mild (G53R,S) and severe (G53D) forms of the disease.
      All examined substitutions (G53D,R,S,A,C,F) reduced ATP-sensitivity, indicating
      an intolerance of any amino acid other than glycine. Surprisingly, each mutation
      reduces ATP affinity, rather than intrinsic gating, although structural modeling
      places G53 at a significant distance from the ATP-binding pocket. We propose that
      glycine is required in this location for flexibility of the distal N-terminus,
      and for an induced fit of ATP at the binding site. Consistent with this
      hypothesis, glycine substitution of the adjacent residue (Q52G) partially rescues
      ATP affinity of reconstituted Q52G/G53D channels. The results reveal an important
      feature of the noncanonical ATP-sensing mechanism of K(ATP) channels.

PMID- 18708461
TI  - Simulations of skin barrier function: free energies of hydrophobic and
      hydrophilic transmembrane pores in ceramide bilayers.
AB  - Transmembrane pore formation is central to many biological processes such as ion
      transport, cell fusion, and viral infection. Furthermore, pore formation in the
      ceramide bilayers of the stratum corneum may be an important mechanism by which
      penetration enhancers such as dimethylsulfoxide (DMSO) weaken the barrier
      function of the skin. We have used the potential of mean constraint force (PMCF)
      method to calculate the free energy of pore formation in ceramide bilayers in
      both the innate gel phase and in the DMSO-induced fluidized state. Our
      simulations show that the fluid phase bilayers form archetypal water-filled
      hydrophilic pores similar to those observed in phospholipid bilayers. In
      contrast, the rigid gel-phase bilayers develop hydrophobic pores. At the
      relatively small pore diameters studied here, the hydrophobic pores are empty
      rather than filled with bulk water, suggesting that they do not compromise the
      barrier function of ceramide membranes. A phenomenological analysis suggests that
      these vapor pores are stable, below a critical radius, because the penalty of
      creating water-vapor and tail-vapor interfaces is lower than that of directly
      exposing the strongly hydrophobic tails to water. The PMCF free energy profile of
      the vapor pore supports this analysis. The simulations indicate that high DMSO
      concentrations drastically impair the barrier function of the skin by strongly
      reducing the free energy required for pore opening.

PMID- 18708462
TI  - Hemoglobin dynamics in red blood cells: correlation to body temperature.
AB  - A transition in hemoglobin behavior at close to body temperature has been
      discovered recently by micropipette aspiration experiments on single red blood
      cells (RBCs) and circular dichroism spectroscopy on hemoglobin solutions. The
      transition temperature was directly correlated to the body temperatures of a
      variety of species. In an exploration of the molecular basis for the transition,
      we present neutron scattering measurements of the temperature dependence of
      hemoglobin dynamics in whole human RBCs in vivo. The data reveal a change in the
      geometry of internal protein motions at 36.9 degrees C, at human body
      temperature. Above that temperature, amino acid side-chain motions occupy larger
      volumes than expected from normal temperature dependence, indicating partial
      unfolding of the protein. Global protein diffusion in RBCs was also measured and
      the findings compared favorably with theoretical predictions for short-time self
      diffusion of noncharged hard-sphere colloids. The results demonstrated that
      changes in molecular dynamics in the picosecond time range and angstrom length
      scale might well be connected to a macroscopic effect on whole RBCs that occurs
      at body temperature.

PMID- 18708463
TI  - Phenomenological model and phase behavior of saturated and unsaturated lipids and
      cholesterol.
AB  - We present a phenomenological theory for the phase behavior of ternary mixtures
      of cholesterol and saturated and unsaturated lipids, one that describes both
      liquid and gel phases. It leads to the following description of the mechanism of
      the phase behavior: In a binary system of the lipids, phase separation occurs
      when the saturated chains are well ordered, as in the gel phase, simply due to
      packing effects. In the liquid phase, the saturated ones are not sufficiently
      well ordered for separation to occur. The addition of cholesterol, however,
      increases the saturated lipid order to the point that phase separation is once
      again favorable. Our theory addresses this last mechanism-the means by which
      cholesterol-mediated ordering of membrane lipids leads to liquid-liquid
      immiscibility. It produces, for the system above the main chain transition of the
      saturated lipid, phase diagrams in which there can be liquid-liquid phase
      separation in the ternary system but not in any of the binary ones, while below
      that temperature it yields the more common phase diagram in which a gel phase,
      rich in saturated lipid, appears in addition to the two liquid phases.

PMID- 18708464
TI  - Long lasting synchronization of calcium oscillations by cholinergic stimulation
      in isolated pancreatic islets.
AB  - Individual mouse pancreatic islets exhibit oscillations in [Ca(2+)](i) and
      insulin secretion in response to glucose in vitro, but how the oscillations of a
      million islets are coordinated within the human pancreas in vivo is unclear.
      Islet to islet synchronization is necessary, however, for the pancreas to produce
      regular pulses of insulin. To determine whether neurohormone release within the
      pancreas might play a role in coordinating islet activity, [Ca(2+)](i) changes in
      4-6 isolated mouse islets were simultaneously monitored before and after a
      transient pulse of a putative synchronizing agent. The degree of synchronicity
      was quantified using a novel analytical approach that yields a parameter that we
      call the "Synchronization Index". Individual islets exhibited [Ca(2+)](i)
      oscillations with periods of 3-6 min, but were not synchronized under control
      conditions. However, raising islet [Ca(2+)](i) with a brief application of the
      cholinergic agonist carbachol (25 microM) or elevated KCl in glucose-containing
      saline rapidly synchronized islet [Ca(2+)](i) oscillations for >/=30 min, long
      after the synchronizing agent was removed. In contrast, the adrenergic agonists
      clonidine or norepinephrine, and the K(ATP) channel inhibitor tolbutamide, failed
      to synchronize islets. Partial synchronization was observed, however, with the
      K(ATP) channel opener diazoxide. The synchronizing action of carbachol depended
      on the glucose concentration used, suggesting that glucose metabolism was
      necessary for synchronization to occur. To understand how transiently perturbing
      islet [Ca(2+)](i) produced sustained synchronization, we used a mathematical
      model of islet oscillations in which complex oscillatory behavior results from
      the interaction between a fast electrical subsystem and a slower metabolic
      oscillator. Transient synchronization simulated by the model was mediated by
      resetting of the islet oscillators to a similar initial phase followed by
      transient "ringing" behavior, during which the model islets oscillated with a
      similar frequency. These results suggest that neurohormone release from
      intrapancreatic neurons could help synchronize islets in situ. Defects in this
      coordinating mechanism could contribute to the disrupted insulin secretion
      observed in Type 2 diabetes.

PMID- 18708465
TI  - Coevolution of function and the folding landscape: correlation with density of
      native contacts.
AB  - The relationship between the folding landscape and function of evolved proteins
      is explored by comparison of the folding mechanisms for members of the flavodoxin
      fold. CheY, Spo0F, and NtrC have unrelated functions and low sequence homology
      but share an identical topology. Recent coarse-grained simulations show that
      their folding landscapes are uniquely tuned to properly suit their respective
      biological functions. Enhanced packing in Spo0F and its limited conformational
      dynamics compared to CheY or NtrC lead to frustration in its folding landscape.
      Simulation as well as experimental results correlate with the local density of
      native contacts for these and a sample of other proteins. In particular, protein
      regions of low contact density are observed to become structured late in folding;
      concomitantly, these dynamic regions are often involved in binding or
      conformational rearrangements of functional importance. These observations help
      to explain the widespread success of Go-like coarse-grained models in reproducing
      protein dynamics.

PMID- 18708466
TI  - Nucleotide capacitance calculation for DNA sequencing.
AB  - Using a first-principles linear response theory, the capacitance of the DNA
      nucleotides, adenine, cytosine, guanine, and thymine, are calculated. The
      difference in the capacitance between the nucleotides is studied with respect to
      conformational distortion. The result suggests that although an alternate current
      capacitance measurement of a single-stranded DNA chain threaded through a nanogap
      electrode may not be sufficient to be used as a standalone method for rapid DNA
      sequencing, the capacitance of the nucleotides should be taken into consideration
      in any GHz-frequency electric measurements and may also serve as an additional
      criterion for identifying the DNA sequence.

PMID- 18708467
TI  - DNA translocation governed by interactions with solid-state nanopores.
AB  - We investigate the voltage-driven translocation dynamics of individual DNA
      molecules through solid-state nanopores in the diameter range 2.7-5 nm. Our
      studies reveal an order of magnitude increase in the translocation times when the
      pore diameter is decreased from 5 to 2.7 nm, and steep temperature dependence,
      nearly threefold larger than would be expected if the dynamics were governed by
      viscous drag. As previously predicted for an interaction-dominated translocation
      process, we observe exponential voltage dependence on translocation times. Mean
      translocation times scale with DNA length by two power laws: for short DNA
      molecules, in the range 150-3500 bp, we find an exponent of 1.40, whereas for
      longer molecules, an exponent of 2.28 dominates. Surprisingly, we find a
      transition in the fraction of ion current blocked by DNA, from a length
      independent regime for short DNA molecules to a regime where the longer the DNA,
      the more current is blocked. Temperature dependence studies reveal that for
      increasing DNA lengths, additional interactions are responsible for the slower
      DNA dynamics. Our results can be rationalized by considering DNA/pore
      interactions as the predominant factor determining DNA translocation dynamics in
      small pores. These interactions markedly slow down the translocation rate,
      enabling higher temporal resolution than observed with larger pores. These
      findings shed light on the transport properties of DNA in small pores, relevant
      for future nanopore applications, such as DNA sequencing and genotyping.

PMID- 18708468
TI  - Neither helix in the coiled coil region of the axle of F1-ATPase plays a
      significant role in torque production.
AB  - F(1)-ATPase is an ATP-driven rotary molecular motor in which the central gamma
      subunit rotates inside the cylinder made of alpha(3)beta(3) subunits. The amino
      and carboxy termini of the gamma-subunit form the axle, an alpha-helical coiled
      coil that deeply penetrates the stator cylinder. We previously truncated the axle
      step by step, starting with the longer carboxy terminus and then cutting both
      termini at the same levels, resulting in a slower yet considerably powerful
      rotation. Here we examine the role of each helix by truncating only the carboxy
      terminus by 25-40 amino-acid residues. Longer truncation impaired the stability
      of the motor complex severely: 40 deletions failed to yield rotating the complex.
      Up to 36 deletions, however, the mutants produced an apparent torque at nearly
      half of the wild-type torque, independent of truncation length. Time-averaged
      rotary speeds were low because of load-dependent stumbling at 120 degrees
      intervals, even with saturating ATP. Comparison with our previous work indicates
      that half the normal torque is produced at the orifice of the stator. The very
      tip of the carboxy terminus adds the other half, whereas neither helix in the
      middle of the axle contributes much to torque generation and the rapid progress
      of catalysis. None of the residues of the entire axle played a specific decisive
      role in rotation.

PMID- 18708469
TI  - Multiple subunit fitting into a low-resolution density map of a macromolecular
      complex using a gaussian mixture model.
AB  - Recently, electron microscopy measurement of single particles has enabled us to
      reconstruct a low-resolution 3D density map of large biomolecular complexes. If
      structures of the complex subunits can be solved by x-ray crystallography at
      atomic resolution, fitting these models into the 3D density map can generate an
      atomic resolution model of the entire large complex. The fitting of multiple
      subunits, however, generally requires large computational costs; therefore,
      development of an efficient algorithm is required. We developed a fast fitting
      program, "gmfit", which employs a Gaussian mixture model (GMM) to represent
      approximated shapes of the 3D density map and the atomic models. A GMM is a
      distribution function composed by adding together several 3D Gaussian density
      functions. Because our model analytically provides an integral of a product of
      two distribution functions, it enables us to quickly calculate the fitness of the
      density map and the atomic models. Using the integral, two types of potential
      energy function are introduced: the attraction potential energy between a 3D
      density map and each subunit, and the repulsion potential energy between
      subunits. The restraint energy for symmetry is also employed to build symmetrical
      origomeric complexes. To find the optimal configuration of subunits, we randomly
      generated initial configurations of subunit models, and performed a steepest
      descent method using forces and torques of the three potential energies.
      Comparison between an original density map and its GMM showed that the required
      number of Gaussian distribution functions for a given accuracy depended on both
      resolution and molecular size. We then performed test fitting calculations for
      simulated low-resolution density maps of atomic models of homodimer, trimer, and
      hexamer, using different search parameters. The results indicated that our method
      was able to rebuild atomic models of a complex even for maps of 30 A resolution
      if sufficient numbers (eight or more) of Gaussian distribution functions were
      employed for each subunit, and the symmetric restraints were assigned for
      complexes with more than three subunits. As a more realistic test, we tried to
      build an atomic model of the GroEL/ES complex by fitting 21-subunit atomic models
      into the 3D density map obtained by cryoelectron microscopy using the C7
      symmetric restraints. A model with low root mean-square deviations (14.7 A) was
      obtained as the lowest-energy model, showing that our fitting method was
      reasonably accurate. Inclusion of other restraints from biological and
      biochemical experiments could further enhance the accuracy.

PMID- 18708470
TI  - Quantitative measurement of cAMP concentration using an exchange protein directly
      activated by a cAMP-based FRET-sensor.
AB  - Forster resonance energy transfer (FRET)-based biosensors for the quantitative
      analysis of intracellular signaling, including sensors for monitoring cyclic
      adenosine monophosphate (cAMP), are of increasing interest. The measurement of
      the donor/acceptor emission ratio in tandem biosensors excited at the donor
      excitation wavelength is a commonly used technique. A general problem, however,
      is that this ratio varies not only with the changes in cAMP concentration but
      also with the changes of the ionic environment or other factors affecting the
      folding probability of the fluorophores. Here, we use a spectral FRET analysis on
      the basis of two excitation wavelengths to obtain a reliable measure of the
      absolute cAMP concentrations with high temporal and spatial resolution by using
      an "exchange protein directly activated by cAMP". In this approach, FRET analysis
      is simplified and does not require additional calibration routines. The change in
      FRET efficiency (E) of the biosensor caused by [cAMP] changes was determined as
      DeltaE = 15%, whereas E varies between 35% at low and 20% at high [cAMP],
      allowing quantitative measurement of cAMP concentration in the range from 150 nM
      to 15 microM. The method described is also suitable for other FRET-based
      biosensors with a 1:1 donor/acceptor stoichiometry. As a proof of principle, we
      measured the specially resolved cAMP concentration within living cells and
      determined the dynamic changes of cAMP levels after stimulation of the Gs-coupled
      serotonin receptor subtype 7 (5-HT7).

PMID- 18708471
TI  - T7 RNA polymerase studied by force measurements varying cofactor concentration.
AB  - RNA polymerases carry out the synthesis of an RNA copy from a DNA template. They
      move along DNA, incorporate nucleotide triphosphate (NTP) at the end of the
      growing RNA chain, and consume chemical energy. In a single-molecule assay using
      the T7 RNA polymerase, we study how a mechanical force opposing the forward
      motion of the enzyme along DNA affects the translocation rate. We also study the
      influence of nucleotide and magnesium concentration on this process. The
      experiment shows that the opposing mechanical force is a competitive inhibitor of
      nucleotide binding. Also, the single-molecule data suggest that magnesium ions
      are involved in a step that does not depend on the external load force. These
      kinetic results associated with known biochemical and mutagenic data, along with
      the static information obtained from crystallographic structures, shape a very
      coherent view of the catalytic cycle of the enzyme: translocation does not take
      place upon NTP binding nor upon NTP cleavage, but rather occurs after PPi release
      and before the next nucleotide binding event. Furthermore, the energetic bias
      associated with the forward motion of the enzyme is close to kT and represents
      only a small fraction of the free energy of nucleotide incorporation and
      pyrophosphate hydrolysis.

PMID- 18708472
TI  - Tryptophan-tryptophan energy migration as a tool to follow apoflavodoxin folding.
AB  - Submolecular details of Azotobacter vinelandii apoflavodoxin (apoFD) (un)folding
      are revealed by time-resolved fluorescence anisotropy using wild-type protein and
      variants lacking one or two of apoFD's three tryptophans. ApoFD equilibrium
      (un)folding by guanidine hydrochloride follows a three-state model: native <-->
      unfolded <--> intermediate. In native protein, W128 is a sink for Forster
      resonance energy transfer (FRET). Consequently, unidirectional FRET with a 50-ps
      transfer correlation time occurs from W167 to W128. FRET from W74 to W167 is much
      slower (6.9 ns). In the intermediate, W128 and W167 have native-like geometry
      because the 50-ps transfer time is observed. However, non-native structure exists
      between W74 and W167 because instead of 6.9 ns the transfer correlation time is
      2.0 ns. In unfolded apoFD this 2.0-ns transfer correlation time is also detected.
      This decrease in transfer correlation time is a result of W74 and W167 becoming
      solvent accessible and randomly oriented toward one another. Apparently W74 and
      W167 are near-natively separated in the folding intermediate and in unfolded
      apoFD. Both tryptophans may actually be slightly closer in space than in the
      native state, even though apoFD's radius increases substantially upon unfolding.
      In unfolded apoFD the 50-ps transfer time observed for native and intermediate
      folding states becomes 200 ps as W128 and W167 are marginally further separated
      than in the native state. Apparently, apoFD's unfolded state is not a featureless
      statistical coil but contains well-defined substructures. The approach presented
      is a powerful tool to study protein folding.

PMID- 18708474
TI  - The association of the ACE gene and elite athletic performance in Israel may be
      an artifact.

PMID- 18708475
TI  - Macrotransposition and other complex chromosomal restructuring in maize by
      closely linked transposons in direct orientation.
AB  - Several observations indicate that compatible ends of separate, yet closely
      linked, transposable elements (TEs) can interact in alternative transposition
      reactions. First, pairs of TEs cause chromosome breaks with frequencies inversely
      related to the intertransposon distance. Second, some combinations of two TEs
      produce complex rearrangements that often include DNA adjacent to one or both
      elements. In pairs of TEs in direct orientation, alternative reactions involving
      the external ends of the two TEs should lead to the transposition of a
      macrotransposon consisting of both elements plus the intervening chromosomal
      segment. Such macrotransposons have been hypothesized previously based on
      deletions, but no macrotransposon insertions have been recovered. To detect
      macrotransposition, we have analyzed heritable chromosomal rearrangements
      produced by a chromosome-breaking pair of Ac and Ds elements situated 6.5 kb
      apart in direct orientation in a part of the maize (Zea mays) genome dispensable
      for viability. Here, we show that the postulated macrotransposon can excise and
      reinsert elsewhere in the genome. In addition, this transposon pair produces
      other complex rearrangements, including deletions, inversions, and reshuffling of
      the intertransposon segment. Thus, closely linked TE pairs, a common
      transposition outcome in some superfamilies, are adept at restructuring
      chromosomes and may have been instrumental in reshaping plant genomes.

PMID- 18708479
TI  - Histidine residue at position 226 is critical for iodide uptake activity of human
      sodium/iodide symporter.
AB  - The sodium/iodide symporter (SLC5A5; also known as NIS), a transmembrane
      glycoprotein principally in the thyroid gland, is responsible for the
      accumulation of iodide necessary for thyroid hormones. Our previous study
      indicated that a novel exon 6 deletion (residues 233-280) in SLC5A5 loses the
      iodide uptake activity. Herein we characterized the role of His-226 in iodide
      transport of SLC5A5. His-226, a highly conserved extracellular residue among
      SLC5A5 homologs, was replaced with alanine, aspartic acid, glutamic acid, or
      lysine. All the SLC5A5 mutants were expressed normally in the cells and targeted
      correctly to the plasma membrane. However, all of the mutants displayed severe
      defects in iodide uptake, suggesting that His-226 was critical for iodide uptake.
      Kinetic analysis further showed that mutation at His-226 led to a dramatic
      decrease in V(max). These findings suggested that the decreased levels of iodide
      uptake activity of SLC5A5 mutants resulted from lower catalytic rates. In
      conclusion, our data first identified the involvement of extracellular charged
      amino acid residue in the iodide uptake ability of SLC5A5.

PMID- 18708477
TI  - Brassinosteroids regulate grain filling in rice.
AB  - Genes controlling hormone levels have been used to increase grain yields in wheat
      (Triticum aestivum) and rice (Oryza sativa). We created transgenic rice plants
      expressing maize (Zea mays), rice, or Arabidopsis thaliana genes encoding sterol
      C-22 hydroxylases that control brassinosteroid (BR) hormone levels using a
      promoter that is active in only the stems, leaves, and roots. The transgenic
      plants produced more tillers and more seed than wild-type plants. The seed were
      heavier as well, especially the seed at the bases of the spikes that fill the
      least. These phenotypic changes brought about 15 to 44% increases in grain yield
      per plant relative to wild-type plants in greenhouse and field trials. Expression
      of the Arabidopsis C-22 hydroxylase in the embryos or endosperms themselves had
      no apparent effect on seed weight. These results suggested that BRs stimulate the
      flow of assimilate from the source to the sink. Microarray and photosynthesis
      analysis of transgenic plants revealed evidence of enhanced CO(2) assimilation,
      enlarged glucose pools in the flag leaves, and increased assimilation of glucose
      to starch in the seed. These results further suggested that BRs stimulate the
      flow of assimilate. Plants have not been bred directly for seed filling traits,
      suggesting that genes that control seed filling could be used to further increase
      grain yield in crop plants.

PMID- 18708476
TI  - RD19, an Arabidopsis cysteine protease required for RRS1-R-mediated resistance,
      is relocalized to the nucleus by the Ralstonia solanacearum PopP2 effector.
AB  - Bacterial wilt, a disease impacting cultivated crops worldwide, is caused by the
      pathogenic bacterium Ralstonia solanacearum. PopP2 (for Pseudomonas outer protein
      P2) is an R. solanacearum type III effector that belongs to the YopJ/AvrRxv
      protein family and interacts with the Arabidopsis thaliana RESISTANT TO RALSTONIA
      SOLANACEARUM 1-R (RRS1-R) resistance protein. RRS1-R contains the
      Toll/Interleukin1 receptor-nucleotide binding site-Leu-rich repeat domains found
      in several cytoplasmic R proteins and a C-terminal WRKY DNA binding domain. In
      this study, we identified the Arabidopsis Cys protease RESPONSIVE TO
      DEHYDRATION19 (RD19) as being a PopP2-interacting protein whose expression is
      induced during infection by R. solanacearum. An Arabidopsis rd19 mutant in an
      RRS1-R genetic background is compromised in resistance to the bacterium,
      indicating that RD19 is required for RRS1-R-mediated resistance. RD19 normally
      localizes in mobile vacuole-associated compartments and, upon coexpression with
      PopP2, is specifically relocalized to the plant nucleus, where the two proteins
      physically interact. No direct physical interaction between RRS1-R and RD19 in
      the presence of PopP2 was detected in the nucleus as determined by Forster
      resonance energy transfer. We propose that RD19 associates with PopP2 to form a
      nuclear complex that is required for activation of the RRS1-R-mediated resistance
      response.

PMID- 18708480
TI  - Self-sampling for oropharyngeal and rectal specimens to screen for sexually
      transmitted infections: acceptability among men who have sex with men.
AB  - OBJECTIVES: To explore the feasibility and acceptability of self-sampling for
      oropharyngeal and rectal specimens to screen for sexually transmitted infections
      (STIs) among men who have sex with men (MSM). Participant's willingness to self
      sample at home was also explored. METHODS: Participants of a study to evaluate
      the sensitivity and specificity of self versus nurse taken oropharyngeal and
      rectal specimens were surveyed to assess the feasibility and acceptability of
      self-sampling using specimen collection methods (gargle, OraSure mouth pad to
      collect oropharyngeal specimens and APTIMA unisex swabs to collect rectal and
      pharyngeal specimens). Acceptability was measured using a five-point Likert-type
      response scale (for example, 1 = strongly disagree; 5 = strongly agree). Open
      ended questions explored participants' experiences of self-sampling. RESULTS: Of
      334 eligible MSM, 301 (90%) participated in the study. Altogether, 301
      participants self-sampled using gargle and rectal and pharyngeal swabs and 288
      using mouth pad. Complete questionnaire data from 274 participants showed that
      feasibility and acceptability of self-sampling using gargle and mouth pad was
      higher (92%) than pharyngeal swabs (76%). Rectal swabs were acceptable to 82%
      participants. Despite some discomfort and difficulty in using swabs, 76% were
      willing to use all four methods for self-sampling in the future. Home sampling
      was acceptable (84%) as it was perceived to be less intrusive and more convenient
      than a clinic visit and likely to reduce genitourinary medicine (GUM) waiting
      time. CONCLUSIONS: Self-sampling for rectal and oropharyngeal specimens is
      feasible and acceptable to MSM. Self-sampling can be offered as an alternative to
      clinic-based testing and has the potential to improve choice, access and uptake
      of screening for STIs.

PMID- 18708481
TI  - Screening pregnant women for chlamydia: what are the predictors of infection?
AB  - OBJECTIVES: To determine the risk factors associated with chlamydial infection in
      pregnancy and the sensitivity and specificity of these when used for selective
      screening. METHODS: A prospective, cross-sectional study of pregnant women aged
      16-25 years attending four major public antenatal services across Melbourne,
      Australia. Between October 2006 and July 2007, women were approached
      consecutively and asked to complete a questionnaire and to provide a first-pass
      urine specimen for Chlamydia trachomatis testing using PCR. RESULTS: Of 1180
      eligible women, 1087 were approached and 1044 (88%) consented to participate.
      Among the 987 women for whom a questionnaire and a definitive diagnostic assay
      were available, the prevalence of chlamydia was 3.2% (95% CI 1.8 to 5.9). In a
      multiple logistic regression model, more than one sexual partner in the past year
      (AOR 11.5; 95% CI 7.1 to 18.5) was associated with chlamydia infection. The use
      of any antibiotic within 3 months (AOR 0.2; 95% CI 0.1 to 0.6) was associated
      with a decreased risk of infection. Screening restricted to women who reported
      more than one sexual partner in the past year would have detected 44% of
      infections in women aged 16-25 years and would have required only 7% of women to
      be screened. The addition of those women aged 20 years and under would have
      required 27% of women to be screened and detection of 72% of infections.
      CONCLUSIONS: Selective chlamydia screening of pregnant women based on risk
      factors can improve the yield from screening. However, the potential harm of
      missed infections among excluded women would need to be considered.

PMID- 18708482
TI  - Nurse-provided screening and brief intervention for risky alcohol consumption by
      sexual health clinic patients.
AB  - OBJECTIVES: Brief intervention for excessive alcohol consumption is effective yet
      not implemented widely. Alcohol misuse is implicated in unsafe sex and sexually
      transmitted infections and is common in clients of sexual health services. Our
      aims were to assess feasibility, acceptability and effectiveness of screening and
      brief intervention for risky alcohol consumption by a nurse in a sexual health
      clinic. METHODS: Patients completed the AUDIT questionnaire on handheld
      computers. Those scoring >or=8 on AUDIT were asked to participate in the study
      and the 3 months' follow-up and were randomised to intervention or control
      groups. The Drink-less package (based on WHO validated methods) was used to
      implement the brief intervention by a trained registered nurse. RESULTS: Of 519
      (87%) who completed screening, 204 (39%) scored >or=8 on AUDIT (eligible), 184
      agreed to follow-up and 133 completed it. At follow-up, both groups showed
      significant reductions in AUDIT scores. Mean scores decreased from 13.7 to 11.5
      (control group) and 14.0 to 10.7 (intervention group); most (94%) recalled the
      intervention and 62% reported reducing drinking compared with 47% of controls
      (p<0.001). The nurse screening and intervention process was reported acceptable
      by 74% of patients at follow-up and a majority (71%) of staff. CONCLUSIONS:
      Screening and brief intervention in a sexual health clinic for risky alcohol
      consumption is feasible, acceptable and effective in producing significant
      reductions in drinking as measured by AUDIT. Both intervention and control groups
      decreased consumption, suggesting that screening alone is sufficient to influence
      behaviour. Further study of brief intervention in this setting is appropriate.

PMID- 18708483
TI  - Prevalence and risk factors for Chlamydia trachomatis infection among cross
      border truck drivers in Hong Kong.
AB  - OBJECTIVES: To determine the prevalence and risk factors for chlamydial infection
      in cross-border truck drivers. METHODS: 225 Hong Kong-based cross-border truck
      drivers were screened for chlamydial infection. Associations between infection
      and potential risk factors were determined by questionnaire. RESULTS: 8.5% of
      drivers were positive for chlamydial infection. Of 62% of drivers reporting
      recent sex with commercial sex workers (CSW), 39% had not used condoms. 75% of
      drivers with extramarital sex partners (ESP) also frequented CSW and 47% of this
      group had not used condoms with CSW. 43.3% PCR-positive cases reported symptoms.
      No risk factor was associated with chlamydial infection after adjustment,
      although "had sex with ESP" approached significance. CONCLUSIONS: The prevalence
      of chlamydial infection among cross-border truck drivers was not strikingly high,
      although drivers engaged in sex with both ESP and CSW, with many admitting
      unprotected intercourse. The findings highlight the importance of promoting safe
      sex to truck drivers.

PMID- 18708484
TI  - Apolipoprotein E-epsilon 4 and recurrent genital herpes in individuals co
      infected with herpes simplex virus type 2 and HIV.
AB  - Apolipoprotein E (APOE) alleles have been associated with the severity of, or
      susceptibility to, infection by various microbes. We investigated the potential
      association between the APOE-epsilon 4 allele and the rate of recurrence of
      genital herpes in patients who were HIV positive and herpes simplex virus type 2
      (HSV-2) seropositive. The APOE-epsilon 4 allele was significantly associated with
      recurrent genital ulceration independent of ethnicity, antiretroviral therapy and
      CD4 count (OR 8.3; 95% CI 2.4 to 28.5). To our knowledge, this is the first
      published study to demonstrate this association and suggests that APOE-epsilon 4
      may represent a future prognostic marker for symptomatic recurrence of genital
      herpes in individuals with HIV.

PMID- 18708485
TI  - Low effectiveness of syndromic treatment services for curable sexually
      transmitted infections in rural South Africa.
AB  - OBJECTIVES: Syndromic sexually transmitted infection (STI) treatment remains a
      cost-saving HIV prevention intervention in many countries in Africa. We estimate
      the effectiveness of syndromic treatment for curable STIs in rural KwaZulu-Natal,
      South Africa, and the trend in STI prevalences before and after the introduction
      of syndromic treatment in 1995. METHODS: Data were available from various
      clinical studies, surveys of public and private health providers, the general
      population and women attending antenatal, family planning and child immunisation
      clinics in rural northern KwaZulu-Natal between 1987 and 2004. Overall
      effectiveness was defined as the estimated proportion of the annual number of
      symptomatic curable STI episodes cured by syndromic treatment based on separate
      estimates for six curable STI aetiologies by gender. RESULTS: Median overall
      effectiveness was 13.1% (95% CI 8.9 to 17.8%) of symptomatic curable STI episodes
      cured. Effectiveness increased to 25.0% (95% CI 17.3 to 33.8%), 47.6% (95% CI
      44.5 to 50.8%) or 14.3% (95% CI 9.9 to 19.4%) if 100% treatment seeking, 100%
      correct treatment provision or 100% cure were assumed, respectively. Time-trends
      were difficult to assess formally but there was little evidence of decreasing STI
      prevalences. Including incurable but treatable herpes simplex virus (HSV)-2
      ulcers in the effectiveness calculation would halve the proportion of ulcers
      cured or correctly treated, but this reduction could be entirely countered by
      including episodic antiviral treatment in the national guidelines. CONCLUSION:
      Overall effectiveness of syndromic treatment for curable STIs in rural KwaZulu
      Natal remains low and there is little evidence of reduced curable STI
      prevalences. As syndromic treatment is likely to be a cost-saving HIV prevention
      intervention in South Africa, innovative strategies are urgently needed to
      increase rates of treatment seeking and correct treatment provision.

PMID- 18708486
TI  - Chlamydia trachomatis OmpA genotyping as a tool for studying the natural history
      of genital chlamydial infection.
AB  - OBJECTIVE: To investigate the relationship of Chlamydia trachomatis (CT) outer
      membrane protein A (OmpA) type to the clearance of CT infection before treatment.
      METHODS: CT OmpA genotyping, with amplification and sequencing of ompA, was
      utilised to study the natural history of CT infection (spontaneous resolution vs
      persistence) in 102 individuals with chlamydia-positive screening tests returning
      for treatment. RESULTS: CT OmpA distribution was associated with spontaneous
      resolution of CT, most notably with CT OmpA genotype J/Ja detected more often
      from the initial screening CT test than other genotypes in those who then had
      spontaneous resolution of CT noted at the time of treatment. Five individuals
      with presumed persisting CT infection had discordant CT OmpA genotypes at the
      screening and treatment visits, suggesting possible new interval CT infection.
      CONCLUSIONS: Clearance of chlamydia by the host before treatment may be
      influenced by the CT OmpA genotype infecting the host. CT OmpA genotyping may be
      a valuable tool in understanding the natural history of chlamydial infections.

PMID- 18708487
TI  - Self and other in schizophrenia: a cognitive neuroscience perspective.
AB  - OBJECTIVE: Recent basic science data indicate that in healthy individuals, self
      referential processing and social cognition rely on common neural substrates. The
      authors assessed self-referential source memory and social cognition in a large
      sample of schizophrenia outpatients and healthy comparison subjects in order to
      compare how these critical processes are associated in the two groups. METHOD:
      Ninety-one schizophrenia outpatients and 30 healthy comparison subjects were
      assessed on measures of basic social cognition and source memory for previously
      learned word items: self-generated, externally presented, and new words. Partial
      correlations and multiple regression analysis were used to test the association
      between social cognition measures and source memory performance and the
      contributions of source memory and general cognitive abilities to a social
      cognition composite score. RESULTS: Schizophrenia patients demonstrated
      significantly lower source memory for self-generated items (self-referential
      source memory) relative to comparison subjects but showed intact external source
      memory. In both groups, self-referential source memory and social cognition
      showed strong correlations. When the effects of general cognitive abilities were
      controlled for, these correlations were attenuated in the schizophrenia patients.
      Regression analysis revealed discrepancies between groups in the cognitive
      functions contributing to social cognition performance. CONCLUSIONS: Impaired
      self-referential source memory represents a unique cognitive deficit in
      schizophrenia. Moreover, the strong association between self-referential source
      memory and social cognition seen in healthy subjects is reduced in schizophrenia
      and is moderated by general cognitive abilities. Impairments in the
      neurocognitive system that underlies both self-referential and social cognition
      provide a parsimonious explanation for the disturbances in the sense of self and
      other that characterize schizophrenia.

PMID- 18708489
TI  - Refining the construct of narcissistic personality disorder: diagnostic criteria
      and subtypes.
AB  - OBJECTIVE: Narcissistic personality disorder has received relatively little
      empirical attention. This study was designed to provide an empirically valid and
      clinically rich portrait of narcissistic personality disorder and to identify
      subtypes of the disorder. METHOD: A random national sample of psychiatrists and
      clinical psychologists (N=1,201) described a randomly selected current patient
      with personality pathology. Clinicians provided detailed psychological
      descriptions of the patients using the Shedler-Westen Assessment Procedure-II
      (SWAP-II), completed a checklist of axis II diagnostic criteria, and provided
      construct ratings for each axis II personality disorder. Descriptions of
      narcissistic patients based on both raw and standardized SWAP-II item scores were
      aggregated to identify, respectively, the most characteristic and the most
      distinctive features of narcissistic personality disorder. RESULTS: A total of
      255 patients met DSM-IV criteria for narcissistic personality disorder based on
      the checklist and 122 based on the construct ratings; 101 patients met criteria
      by both methods. Q-factor analysis identified three subtypes of narcissistic
      personality disorder, which the authors labeled grandiose/malignant, fragile, and
      high-functioning/exhibitionistic. Core features of the disorder included
      interpersonal vulnerability and underlying emotional distress, along with anger,
      difficulty in regulating affect, and interpersonal competitiveness, features that
      are absent from the DSM-IV description of narcissistic personality disorder.
      CONCLUSIONS: These findings suggest that DSM-IV criteria for narcissistic
      personality disorder are too narrow, underemphasizing aspects of personality and
      inner experience that are empirically central to the disorder. The richer and
      more differentiated view of narcissistic personality disorder suggested by this
      study may have treatment implications and may help bridge the gap between
      empirically and clinically derived concepts of the disorder.

PMID- 18708488
TI  - Does bereavement-related major depression differ from major depression associated
      with other stressful life events?
AB  - OBJECTIVE: Of the stressful life events influencing risk for major depression,
      DSM-III and DSM-IV assign a special status to bereavement. A depressive episode
      that is bereavement-related and has clinical features and course characteristic
      of normal grief is not diagnosed as major depression. This study evaluates the
      empirical validity of this exclusion criterion. METHOD: To determine the
      similarities of bereavement-related depression and depression related to other
      stressful life events, the authors identified and compared cases on a range of
      validators in a large-population-based sample of twins. The authors evaluated
      whether cases of bereavement-related depression that also met DSM criteria for
      "normal grief" were qualitatively distinct from other depressive cases. RESULTS:
      Eighty-two individuals with confirmed bereavement-related depression and 224 with
      confirmed depression related to other stressful life events were identified. The
      two groups did not differ in age at onset of major depression, number of prior
      episodes, duration of index episode, number of endorsed "A criteria," risk for
      future episodes, pattern of comorbidity, levels of extraversion, risk for major
      depression in their co-twin, or the proportion meeting criteria for "normal
      grief." However, individuals with bereavement-related depression were slightly
      older, and more likely to be female, and had lower levels of neuroticism,
      treatment-seeking, and guilt and higher levels of fatigue and loss of interest.
      Interaction analyses failed to find unique features of people whose illness met
      criteria for both bereavement-related depression and normal grief compared to
      those whose illness was related to other life stressors. CONCLUSIONS: The
      similarities between bereavement-related depression and depression related to
      other stressful life events substantially outweigh their differences. These
      results question the validity of the bereavement exclusion for the diagnosis of
      major depression.

PMID- 18708490
TI  - Firing first: compensatory changes in K+ channel knockout mice preserve
      excitability but not synaptic scaling.

PMID- 18708491
TI  - Repetitive transcranial magnetic stimulation: faster or longer is not necessarily
      more.

PMID- 18708492
TI  - New insights into the structure and function of couplons.

PMID- 18708493
TI  - The role of GABA and glutamate on adult neurogenesis.

PMID- 18708494
TI  - O2- and NO-sensing mechanism through the DevSR two-component system in
      Mycobacterium smegmatis.
AB  - The DevS histidine kinase of Mycobacterium smegmatis contains tandem GAF domains
      (GAF-A and GAF-B) in its N-terminal sensory domain. The heme iron of DevS is in
      the ferrous state when purified and is resistant to autooxidation from a ferrous
      to a ferric state in the presence of O(2). The redox property of the heme and the
      results of sequence comparison analysis indicate that DevS of M. smegmatis is
      more closely related to DosT of Mycobacterium tuberculosis than DevS of M.
      tuberculosis. The binding of O(2) to the deoxyferrous heme led to a decrease in
      the autokinase activity of DevS, whereas NO binding did not. The regulation of
      DevS autokinase activity in response to O(2) and NO was not observed in the DevS
      derivatives lacking its heme, indicating that the ligand-binding state of the
      heme plays an important role in the regulation of DevS kinase activity. The redox
      state of the quinone/quinol pool of the respiratory electron transport chain
      appears not to be implicated in the regulation of DevS activity. Neither cyclic
      GMP (cGMP) nor cAMP affected DevS autokinase activity, excluding the possibility
      that the cyclic nucleotides serve as the effector molecules to modulate DevS
      kinase activity. The three-dimensional structure of the putative GAF-B domain
      revealed that it has a GAF folding structure without cyclic nucleotide binding
      capacity.

PMID- 18708495
TI  - Involvement of an essential gene, mviN, in murein synthesis in Escherichia coli.
AB  - We isolated a temperature-sensitive mutant with a mutation in mviN, an essential
      gene in Escherichia coli. At the nonpermissive temperature, mviN mutant cells
      swelled and burst. An intermediate in murein synthesis, polyprenyl diphosphate-N
      acetylmuramic acid-(pentapeptide)-N-acetyl-glucosamine, accumulated in mutant
      cells. These results indicated that MviN is involved in murein synthesis.

PMID- 18708496
TI  - Substrate specificities and availability of fucosyltransferase and beta-carotene
      hydroxylase for myxol 2'-fucoside synthesis in Anabaena sp. strain PCC 7120
      compared with Synechocystis sp. strain PCC 6803.
AB  - To elucidate the biosynthetic pathways of carotenoids, especially myxol 2'
      glycosides, in cyanobacteria, Anabaena sp. strain PCC 7120 (also known as Nostoc
      sp. strain PCC 7120) and Synechocystis sp. strain PCC 6803 deletion mutants
      lacking selected proposed carotenoid biosynthesis enzymes and GDP-fucose synthase
      (WcaG), which is required for myxol 2'-fucoside production, were analyzed. The
      carotenoids in these mutants were identified using high-performance liquid
      chromatography, field desorption mass spectrometry, and (1)H nuclear magnetic
      resonance. The wcaG (all4826) deletion mutant of Anabaena sp. strain PCC 7120
      produced myxol 2'-rhamnoside and 4-ketomyxol 2'-rhamnoside as polar carotenoids
      instead of the myxol 2'-fucoside and 4-ketomyxol 2'-fucoside produced by the wild
      type. Deletion of the corresponding gene in Synechocystis sp. strain PCC 6803
      (sll1213; 79% amino acid sequence identity with the Anabaena sp. strain PCC 7120
      gene product) produced free myxol instead of the myxol 2'-dimethyl-fucoside
      produced by the wild type. Free myxol might correspond to the unknown component
      observed previously in the same mutant (H. E. Mohamed, A. M. L. van de Meene, R.
      W. Roberson, and W. F. J. Vermaas, J. Bacteriol. 187:6883-6892, 2005). These
      results indicate that in Anabaena sp. strain PCC 7120, but not in Synechocystis
      sp. strain PCC 6803, rhamnose can be substituted for fucose in myxol glycoside.
      The beta-carotene hydroxylase orthologue (CrtR, Alr4009) of Anabaena sp. strain
      PCC 7120 catalyzed the transformation of deoxymyxol and deoxymyxol 2'-fucoside to
      myxol and myxol 2'-fucoside, respectively, but not the beta-carotene-to
      zeaxanthin reaction, whereas CrtR from Synechocystis sp. strain PCC 6803
      catalyzed both reactions. Thus, the substrate specificities or substrate
      availabilities of both fucosyltransferase and CrtR were different in these
      species. The biosynthetic pathways of carotenoids in Anabaena sp. strain PCC 7120
      are discussed.

PMID- 18708497
TI  - Interplay between cyclic AMP-cyclic AMP receptor protein and cyclic di-GMP
      signaling in Vibrio cholerae biofilm formation.
AB  - Vibrio cholerae is a facultative human pathogen. The ability of V. cholerae to
      form biofilms is crucial for its survival in aquatic habitats between epidemics
      and is advantageous for host-to-host transmission during epidemics. Formation of
      mature biofilms requires the production of extracellular matrix components,
      including Vibrio polysaccharide (VPS) and matrix proteins. Biofilm formation is
      positively controlled by the transcriptional regulators VpsR and VpsT and is
      negatively regulated by the quorum-sensing transcriptional regulator HapR, as
      well as the cyclic AMP (cAMP)-cAMP receptor protein (CRP) regulatory complex.
      Transcriptome analysis of cyaA (encoding adenylate cyclase) and crp (encoding
      cAMP receptor protein) deletion mutants revealed that cAMP-CRP negatively
      regulates transcription of both VPS biosynthesis genes and genes encoding biofilm
      matrix proteins. Further mutational and expression analysis revealed that cAMP
      CRP negatively regulates transcription of vps genes indirectly through its action
      on vpsR transcription. However, negative regulation of the genes encoding biofilm
      matrix proteins by cAMP-CRP can also occur independent of VpsR. Transcriptome
      analysis also revealed that cAMP-CRP regulates the expression of a set of genes
      encoding diguanylate cyclases (DGCs) and phosphodiesterases. Mutational and
      phenotypic analysis of the differentially regulated DGCs revealed that a DGC,
      CdgA, is responsible for the increase in biofilm formation in the Deltacrp
      mutant, showing the connection between of cyclic di-GMP and cAMP signaling in V.
      cholerae.

PMID- 18708498
TI  - Integrative conjugative elements and related elements are major contributors to
      the genome diversity of Streptococcus agalactiae.
AB  - Thirty-five putative integrative conjugative elements and related elements were
      identified at 15 locations in the eight sequenced genomes of Streptococcus
      agalactiae. Twelve are composite, likely resulting from site-specific accretions.
      Circular forms were detected for five elements. Macroarray analysis confirmed
      their high plasticity and wide distribution in S. agalactiae.

PMID- 18708499
TI  - The yiaKLX1X2PQRS and ulaABCDEFG gene systems are required for the aerobic
      utilization of L-ascorbate in Klebsiella pneumoniae strain 13882 with L-ascorbate
      6-phosphate as the inducer.
AB  - The capacity to both ferment and oxidize L-ascorbate has been widely documented
      for a number of enteric bacteria. Here we present evidence that all the strains
      of Klebsiella pneumoniae tested in this study ferment L-ascorbate using the ula
      regulon-encoded proteins. Under aerobic conditions, several phenotypes were
      observed for the strains. Our results showed that the yiaK-S system is required
      for this aerobic metabolic process. Gel shift experiments performed with UlaR and
      YiaJ and probes corresponding to the specific promoters indicated that L
      ascorbate-6-phosphate is the effector molecule recognized by both regulators,
      since binding of the repressors to their recognition sites was impaired by the
      presence of this compound. We demonstrated that in K. pneumoniae cells L
      ascorbate-6-phosphate is formed only by the action of the UlaABC
      phosphotransferase system. This finding explains why strains that lack the ula
      genetic system and therefore are unable to form the inducer intracellularly
      cannot efficiently use this vitamin as a carbon source under either anaerobic or
      aerobic conditions. Thus, efficient aerobic metabolism of L-ascorbate in K.
      pneumoniae is dependent on the presence of both the yiaK-S and ula systems. The
      expression of the yiaK-S operon, but not the expression of the ula regulon, is
      controlled by oxygen availability. Both systems are regulated by the cyclic AMP
      (cAMP)-cAMP receptor protein (CRP) complex and by IHF.

PMID- 18708500
TI  - Role of premature stop codons in bacterial evolution.
AB  - When the stop codons TGA, TAA, and TAG are found in the second and third reading
      frames of a protein-encoding gene, they are considered premature stop codons
      (PSC). Deinococcus radiodurans disproportionately favored TGA more than the other
      two triplets as a PSC. The TGA triplet was also found more often in noncoding
      regions and as a stop codon, though the bias was less pronounced. We investigated
      this phenomenon in 72 bacterial species with widely differing chromosomal GC
      contents. Although TGA and TAG were compositionally similar, we found a great
      variation in use of TGA but a very limited range of use of TAG. The frequency of
      use of TGA in the gene sequences generally increased with the GC content of the
      chromosome, while the frequency of use of TAG, like that of TAA, was inversely
      proportional to the GC content of the chromosome. The patterns of use of TAA, TGA
      and TAG as real stop codons were less biased and less influenced by the GC
      content of the chromosome. Bacteria with higher chromosomal GC contents often
      contained fewer PSC trimers in their genes. Phylogenetically related bacteria
      often exhibited similar PSC ratios. In addition, metabolically versatile bacteria
      have significantly fewer PSC trimers in their genes. The bias toward TGA but
      against TAG as a PSC could not be explained either by the preferential usage of
      specific codons or by the GC contents of individual chromosomes. We proposed that
      the quantity and the quality of the PSC in the genome might be important in
      bacterial evolution.

PMID- 18708501
TI  - The tie that binds the dynamic duo: the connector between AS1 and AS2 in the HAMP
      domain of the Escherichia coli Tsr chemoreceptor.

PMID- 18708502
TI  - Characterization of the putative type III secretion ATPase CdsN (Cpn0707) of
      Chlamydophila pneumoniae.
AB  - Type III secretion (T3S) is utilized by a wide range of gram-negative bacterial
      pathogens to allow the efficient delivery of effector proteins into the host cell
      cytoplasm through the use of a syringe-like injectisome. Chlamydophila pneumoniae
      is a gram-negative, obligate intracellular pathogen that has the structural genes
      coding for a T3S system, but the functionality of the system has not yet been
      demonstrated. T3S is dependent on ATPase activity, which catalyzes the unfolding
      of proteins and the secretion of effector proteins through the injectisome. CdsN
      (Cpn0707) is predicted to be the T3S ATPase of C. pneumoniae based on sequence
      similarity to other T3S ATPases. Full-length CdsN and a C-terminal truncation of
      CdsN were cloned as glutathione S-transferase (GST)-tagged constructs and
      expressed in Escherichia coli. The GST-tagged C-terminal truncation of CdsN
      possessed ATPase activity, catalyzing the release of ADP and P(i) from ATP at a
      rate of 0.55 +/- 0.07 micromol min(-1) mg(-1) in a time- and dose-dependent
      manner. CdsN formed oligomers and high-molecular-weight multimers, as assessed by
      formaldehyde fixation and nondenaturing polyacrylamide gel electrophoresis. Using
      bacterial two-hybrid and GST pull-down assays, CdsN was shown to interact with
      CdsD, CdsL, CdsQ, and CopN, four putative structural components of the C.
      pneumoniae T3S system. CdsN also interacted with an unannotated protein, Cpn0706,
      a putative CdsN chaperone. Interactions between CdsN, CdsD, and CopN represent
      novel interactions not previously reported for other bacterial T3S systems and
      may be important in the localization and/or function of the ATPase at the inner
      membrane of C. pneumoniae.

PMID- 18708503
TI  - Adaptation of aerobically growing Pseudomonas aeruginosa to copper starvation.
AB  - Restricted bioavailability of copper in certain environments can interfere with
      cellular respiration because copper is an essential cofactor of most terminal
      oxidases. The global response of the metabolically versatile bacterium and
      opportunistic pathogen Pseudomonas aeruginosa to copper limitation was assessed
      under aerobic conditions. Expression of cioAB (encoding an alternative, copper
      independent, cyanide-resistant ubiquinol oxidase) was upregulated, whereas
      numerous iron uptake functions (including the siderophores pyoverdine and
      pyochelin) were expressed at reduced levels, presumably reflecting a lower demand
      for iron by respiratory enzymes. Wild-type P. aeruginosa was able to grow
      aerobically in a defined glucose medium depleted of copper, whereas a cioAB
      mutant did not grow. Thus, P. aeruginosa relies on the CioAB enzyme to cope with
      severe copper deprivation. A quadruple cyo cco1 cco2 cox mutant, which was
      deleted for all known heme-copper terminal oxidases of P. aeruginosa, grew
      aerobically, albeit more slowly than did the wild type, indicating that the CioAB
      enzyme is capable of energy conservation. However, the expression of a cioA'
      'lacZ fusion was less dependent on the copper status in the quadruple mutant than
      in the wild type, suggesting that copper availability might affect cioAB
      expression indirectly, via the function of the heme-copper oxidases.

PMID- 18708504
TI  - Insights into the environmental resistance gene pool from the genome sequence of
      the multidrug-resistant environmental isolate Escherichia coli SMS-3-5.
AB  - The increasing occurrence of multidrug-resistant pathogens of clinical and
      agricultural importance is a global public health concern. While antimicrobial
      use in human and veterinary medicine is known to contribute to the dissemination
      of antimicrobial resistance, the impact of microbial communities and mobile
      resistance genes from the environment in this process is not well understood.
      Isolated from an industrially polluted aquatic environment, Escherichia coli SMS
      3-5 is resistant to a record number of antimicrobial compounds from all major
      classes, including two front-line fluoroquinolones (ciprofloxacin and
      moxifloxacin), and in many cases at record-high concentrations. To gain insights
      into antimicrobial resistance in environmental bacterial populations, the genome
      of E. coli SMS-3-5 was sequenced and compared to the genome sequences of other E.
      coli strains. In addition, selected genetic loci from E. coli SMS-3-5 predicted
      to be involved in antimicrobial resistance were phenotypically characterized.
      Using recombinant vector clones from shotgun sequencing libraries, resistance to
      tetracycline, streptomycin, and sulfonamide/trimethoprim was assigned to a single
      mosaic region on a 130-kb plasmid (pSMS35_130). The remaining plasmid backbone
      showed similarity to virulence plasmids from avian-pathogenic E. coli (APEC)
      strains. Individual resistance gene cassettes from pSMS35_130 are conserved among
      resistant bacterial isolates from multiple phylogenetic and geographic sources.
      Resistance to quinolones was assigned to several chromosomal loci, mostly
      encoding transport systems that are also present in susceptible E. coli isolates.
      Antimicrobial resistance in E. coli SMS-3-5 is therefore dependent both on
      determinants acquired from a mobile gene pool that is likely available to
      clinical and agricultural pathogens, as well, and on specifically adapted
      multidrug efflux systems. The association of antimicrobial resistance with APEC
      virulence genes on pSMS35_130 highlights the risk of promoting the spread of
      virulence through the extensive use of antibiotics.

PMID- 18708505
TI  - Molecular characterization of a Clostridium difficile bacteriophage and its
      cloned biologically active endolysin.
AB  - Clostridium difficile infection is increasing in both frequency and severity,
      with the emergence of new highly virulent strains highlighting the need for more
      rapid and effective methods of control. Here, we show that bacteriophage
      endolysin can be used to inhibit and kill C. difficile. The genome sequence of a
      novel bacteriophage that is active against C. difficile was determined, and the
      bacteriophage endolysin gene was subcloned and expressed in Escherichia coli. The
      partially purified endolysin was active against 30 diverse strains of C.
      difficile, and importantly, this group included strains of the major epidemic
      ribotype 027 (B1/NAP1). In contrast, a range of commensal species that inhabit
      the gastrointestinal tract, including several representatives of the clostridium
      like Firmicutes, were insensitive to the endolysin. This endolysin provides a
      platform for the generation of both therapeutic and detection systems to combat
      the C. difficile problem. To investigate a method for the protected delivery and
      production of the lysin in the gastrointestinal tract, we demonstrated the
      expression of active CD27L endolysin in the lactic acid bacterium Lactococcus
      lactis MG1363.

PMID- 18708506
TI  - Sinorhizobium meliloti mutants deficient in phosphatidylserine decarboxylase
      accumulate phosphatidylserine and are strongly affected during symbiosis with
      alfalfa.
AB  - Sinorhizobium meliloti contains phosphatidylglycerol, cardiolipin,
      phosphatidylcholine, and phosphatidylethanolamine (PE) as major membrane lipids.
      PE is formed in two steps. In the first step, phosphatidylserine synthase (Pss)
      condenses serine with CDP-diglyceride to form phosphatidylserine (PS), and in the
      second step, PS is decarboxylated by phosphatidylserine decarboxylase (Psd) to
      form PE. In this study we identified the sinorhizobial psd gene coding for Psd. A
      sinorhizobial mutant deficient in psd is unable to form PE but accumulates the
      anionic phospholipid PS. Properties of PE-deficient mutants lacking either Pss or
      Psd were compared with those of the S. meliloti wild type. Whereas both PE
      deficient mutants grew in a wild-type-like manner on many complex media, they
      were unable to grow on minimal medium containing high phosphate concentrations.
      Surprisingly, the psd-deficient mutant could grow on minimal medium containing
      low concentrations of inorganic phosphate, while the pss-deficient mutant could
      not. Addition of choline to the minimal medium rescued growth of the pss
      deficient mutant, CS111, to some extent but inhibited growth of the psd-deficient
      mutant, MAV01. When the two distinct PE-deficient mutants were analyzed for their
      ability to form a nitrogen-fixing root nodule symbiosis with their alfalfa host
      plant, they behaved strikingly differently. The Pss-deficient mutant, CS111,
      initiated nodule formation at about the same time point as the wild type but did
      form about 30% fewer nodules than the wild type. In contrast, the PS-accumulating
      mutant, MAV01, initiated nodule formation much later than the wild type and
      formed 90% fewer nodules than the wild type. The few nodules formed by MAV01
      seemed to be almost devoid of bacteria and were unable to fix nitrogen. Leaves of
      alfalfa plants inoculated with the mutant MAV01 were yellowish, indicating that
      the plants were starved for nitrogen. Therefore, changes in lipid composition,
      including the accumulation of bacterial PS, prevent the establishment of a
      nitrogen-fixing root nodule symbiosis.

PMID- 18708507
TI  - Interaction of penicillin-binding protein 2 with soluble lytic transglycosylase
      B1 in Pseudomonas aeruginosa.
AB  - Soluble lytic transglycosylase B1 from Pseudomonas aeruginosa was coupled to
      Sepharose and used to immobilize interaction partners from membrane protein
      extracts. Penicillin-binding protein 2 (PBP2) was identified as a binding
      partner, suggesting that the two proteins function together in the biosynthesis
      of peptidoglycan. By use of an engineered truncated derivative, the N-terminal
      module of PBP2 was found to confer the binding properties.

PMID- 18708508
TI  - Ectopic expression of serotonin7 receptors in an adrenocortical carcinoma co
      secreting renin and cortisol.
AB  - Abnormal expression of membrane receptors has been previously described in benign
      adrenocortical neoplasms causing Cushing's syndrome. In particular, we have
      observed that, in some adreno corticotropic hormone (ACTH)-independent
      macronodular adrenal hyperplasia tissues, cortisol secretion is controlled by
      ectopic serotonin(7) (5-HT(7)) receptors. The objective of the present study was
      to investigate in vitro the effect of serotonin (5-hydroxy tryptamine; 5-HT) on
      cortisol and renin production by a left adrenocortical carcinoma removed from a
      48-year-old female patient with severe Cushing's syndrome and elevated plasma
      renin levels. Tumor explants were obtained at surgery and processed for
      immunohistochemistry, in situ hybridization and cell culture studies. 5-HT-like
      immunoreactivity was observed in mast cells and steroidogenic cells disseminated
      in the tissue. 5-HT stimulated cortisol release by cultured cells. The
      stimulatory effect of 5-HT on cortisol secretion was suppressed by the 5-HT(7)
      receptor antagonist SB269970. In addition, immunohistochemistry showed the
      occurrence of 5-HT(7) receptor-like immunoreactivity in carcinoma cells. mRNAs
      encoding renin as well as renin-like immunoreactivity were detected in
      endothelial and tumor cells. Cell incubation studies revealed that the
      adrenocortical tissue also released renin. Renin production was inhibited by 5-HT
      but was not influenced by ACTH and angiotensin II (Ang II). In conclusion, the
      present report provides the first demonstration of ectopic serotonin receptors,
      i.e. 5-HT(7) receptors, in an adrenocortical carcinoma. Our results also indicate
      that 5-HT can influence the secretory activity of malignant adrenocortical tumors
      in an autocrine/paracrine manner. The effects of 5-HT on adrenocortical tumor
      cells included a paradoxical inhibitory action on renin production and a
      stimulatory action on cortisol secretion involving 5-HT(7) receptors.

PMID- 18708509
TI  - Climate patterns governing the presence and permanence of salmonellae in coastal
      areas of Bahia de Todos Santos, Mexico.
AB  - Despite the importance of salmonellae as one of the major causes of food-borne
      infections worldwide, data regarding the presence of these organisms in the
      environment are limited. We investigated the presence of Salmonella spp. in Bahia
      de Todos Santos (Baja California, Mexico) and evaluated the environmental factors
      that affect the occurrence of Salmonella spp. in this arid region. A total of
      1,331 samples collected from 21 sites along the coast during a period of 3 years
      were analyzed for Salmonella spp. Geographical and seasonal distribution of
      Salmonella spp. was evaluated in association with environmental parameters and
      with human infections in the area. The incidence of Salmonella bacteria
      throughout the study was 4.8%, with the highest incidence detected in wastewater
      (16.2%), followed by stream water (10.6%), mollusks (7.4%), and seawater (2.3%).
      Twenty different serotypes were identified among the 64 Salmonella isolates. The
      dominant serotype was Typhimurium (23.4%), followed by Vejle (6.2%). The presence
      of Salmonella spp. in coastal areas was mostly confined to rainy periods and
      areas of stream discharges, and runoff was identified as the predominant factor
      influencing the transport of Salmonella bacteria from source points to the sea
      via streams. Isolation of Salmonella spp. was negatively and significantly
      associated with temperature, probably because of the effect of solar radiation in
      the decline of permanence of Salmonella bacteria. Conversely, human infections
      prevailed during the warmest months and were negatively correlated with the
      presence of Salmonella spp. in the marine environment.

PMID- 18708510
TI  - Characterization of the Pseudomonas pseudoalcaligenes CECT5344 Cyanase, an enzyme
      that is not essential for cyanide assimilation.
AB  - Cyanase catalyzes the decomposition of cyanate into CO(2) and ammonium, with
      carbamate as an unstable intermediate. The cyanase of Pseudomonas
      pseudoalcaligenes CECT5344 was negatively regulated by ammonium and positively
      regulated by cyanate, cyanide, and some cyanometallic complexes. Cyanase activity
      was not detected in cell extracts from cells grown with ammonium, even in the
      presence of cyanate. Nevertheless, a low level of cyanase activity was detected
      in nitrogen-starved cells. The cyn gene cluster of P. pseudoalcaligenes CECT5344
      was cloned and analyzed. The cynA, cynB, and cynD genes encode an ABC-type
      transporter, the cynS gene codes for the cyanase, and the cynF gene encodes a
      novel sigma(54)-dependent transcriptional regulator which is not present in other
      bacterial cyn gene clusters. The CynS protein was expressed in Escherichia coli
      and purified by following a simple and rapid protocol. The P. pseudoalcaligenes
      cyanase showed an optimal pH of 8.5 degrees C and a temperature of 65 degrees C.
      An insertion mutation was generated in the cynS gene. The resulting mutant was
      unable to use cyanate as the sole nitrogen source but showed the same resistance
      to cyanate as the wild-type strain. These results, in conjunction with the
      induction pattern of the enzymatic activity, suggest that the enzyme has an
      assimilatory function. Although the induction of cyanase activity in cyanide
      degrading cells suggests that some cyanate may be generated from cyanide, the
      cynS mutant was not affected in its ability to degrade cyanide, which
      unambiguously indicates that cyanate is not a central metabolite in cyanide
      assimilation.

PMID- 18708512
TI  - Resolution of culture Clostridium bifermentans DPH-1 into two populations, a
      Clostridium sp. and tetrachloroethene-dechlorinating Desulfitobacterium hafniense
      strain JH1.
AB  - Clostridium bifermentans strain DPH-1 reportedly dechlorinates tetrachloroethene
      (PCE) to cis-1,2-dichloroethene. Cultivation-based approaches resolved the DPH-1
      culture into two populations: a nondechlorinating Clostridium sp. and PCE
      dechlorinating Desulfitobacterium hafniense strain JH1. Strain JH1 carries pceA,
      encoding a PCE reductive dehalogenase, and shares other characteristics with
      Desulfitobacterium hafniense strain Y51.

PMID- 18708513
TI  - Quantitative real-time reverse transcription-PCR analysis reveals stable and
      prolonged neurotoxin cluster gene activity in a Clostridium botulinum type E
      strain at refrigeration temperature.
AB  - The relative expression levels of six botulinum neurotoxin cluster genes in a
      group II Clostridium botulinum type E strain grown at 10 or 30 degrees C were
      investigated using quantitative real-time reverse transcription-PCR. An enzyme
      linked immunosorbent assay was used to confirm neurotoxin expression. Distinct
      mRNA and toxin production patterns were observed at the two temperatures. The
      average relative mRNA levels at 10 degrees C were higher than (ntnh and p47),
      similar to (botE), or lower than (orfx1, orfx2, orfx3) those at 30 degrees C. The
      maximum botE expression levels and average neurotoxin levels at 10 degrees C were
      45 to 65% of those at 30 degrees C. The relative mRNA levels at 10 degrees C
      declined generally slowly within 8 days, as opposed to the rapid decline observed
      at 30 degrees C within 24 h. Distinct expression patterns of the six genes at the
      two temperatures suggest that the type E neurotoxin cluster genes are transcribed
      as two tricistronic operons at 30 degrees C, whereas at 10 degrees C
      monocistronic (botE or orfx1 alone) and bicistronic (ntnh-p47 and orfx2-orfx3)
      transcription may dominate. Thus, type E botulinum neurotoxin production may be
      involved with various temperature-dependent regulatory events. In light of group
      II C. botulinum type E being a dangerous food-borne pathogen, these findings may
      be important in terms of the safety of refrigerated packaged foods of extended
      durability.

PMID- 18708514
TI  - Controlled expression of the dominant flocculation genes FLO1, FLO5, and FLO11 in
      Saccharomyces cerevisiae.
AB  - In many industrial fermentation processes, the Saccharomyces cerevisiae yeast
      should ideally meet two partially conflicting demands. During fermentation, a
      high suspended yeast count is required to maintain a satisfactory rate of
      fermentation, while at completion, efficient settling is desired to enhance
      product clarification and recovery. In most fermentation industries, currently
      used starter cultures do not satisfy this ideal, probably because nonflocculent
      yeast strains were selected to avoid fermentation problems. In this paper, we
      assess molecular strategies to optimize the flocculation behavior of S.
      cerevisiae. For this purpose, the chromosomal copies of three dominant
      flocculation genes, FLO1, FLO5, and FLO11, of the haploid nonflocculent,
      noninvasive, and non-flor-forming S. cerevisiae FY23 strain were placed under the
      transcriptional control of the promoters of the ADH2 and HSP30 genes. All six
      promoter-gene combinations resulted in specific flocculation behaviors in terms
      of timing and intensity. The strategy resulted in stable expression patterns
      providing a platform for the direct comparison and assessment of the specific
      impact of the expression of individual dominant FLO genes with regard to cell
      wall characteristics, such as hydrophobicity, biofilm formation, and substrate
      adhesion properties. The data also clearly demonstrate that the flocculation
      behavior of yeast strains can be tightly controlled and fine-tuned to satisfy
      specific industrial requirements.

PMID- 18708511
TI  - Amplification of uncultured single-stranded DNA viruses from rice paddy soil.
AB  - Viruses are known to be the most numerous biological entities in soil; however,
      little is known about their diversity in this environment. In order to explore
      the genetic diversity of soil viruses, we isolated viruses by centrifugation and
      sequential filtration before performing a metagenomic investigation. We adopted
      multiple-displacement amplification (MDA), an isothermal whole-genome
      amplification method with phi29 polymerase and random hexamers, to amplify viral
      DNA and construct clone libraries for metagenome sequencing. By the MDA method,
      the diversity of both single-stranded DNA (ssDNA) viruses and double-stranded DNA
      viruses could be investigated at the same time. On the contrary, by eliminating
      the denaturing step in the MDA reaction, only ssDNA viral diversity could be
      explored selectively. Irrespective of the denaturing step, more than 60% of the
      soil metagenome sequences did not show significant hits (E-value criterion,
      0.001) with previously reported viral sequences. Those hits that were considered
      to be significant were also distantly related to known ssDNA viruses (average
      amino acid similarity, approximately 34%). Phylogenetic analysis showed that
      replication-related proteins (which were the most frequently detected proteins)
      related to those of ssDNA viruses obtained from the metagenomic sequences were
      diverse and novel. Putative circular genome components of ssDNA viruses that are
      unrelated to known viruses were assembled from the metagenomic sequences. In
      conclusion, ssDNA viral diversity in soil is more complex than previously
      thought. Soil is therefore a rich pool of previously unknown ssDNA viruses.

PMID- 18708515
TI  - Differentiation of Streptococcus pneumoniae conjunctivitis outbreak isolates by
      matrix-assisted laser desorption ionization-time of flight mass spectrometry.
AB  - Streptococcus pneumoniae (pneumococcus [Pnc]) is a causative agent of many
      infectious diseases, including pneumonia, septicemia, otitis media, and
      conjunctivitis. There have been documented conjunctivitis outbreaks in which
      nontypeable (NT), nonencapsulated Pnc has been identified as the etiological
      agent. The use of mass spectrometry to comparatively and differentially analyze
      protein and peptide profiles of whole-cell microorganisms remains somewhat
      uncharted. In this report, we discuss a comparative proteomic analysis between NT
      S. pneumoniae conjunctivitis outbreak strains (cPnc) and other known typeable or
      NT pneumococcal and streptococcal isolates (including Pnc TIGR4 and R6,
      Streptococcus oralis, Streptococcus mitis, Streptococcus pseudopneumoniae, and
      Streptococcus pyogenes) and nonstreptococcal isolates (including Escherichia
      coli, Enterococcus faecalis, and Staphylococcus aureus) as controls. cPnc cells
      and controls were grown to mid-log phase, harvested, and subsequently treated
      with a 10% trifluoroacetic acid-sinapinic acid matrix mixture. Protein and
      peptide fragments of the whole-cell bacterial isolate-matrix combinations ranging
      in size from 2 to 14 kDa were evaluated by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry. Additionally Random Forest
      analytical tools and dendrogramic representations (Genesis) suggested
      similarities and clustered the isolates into distinct clonal groups,
      respectively. Also, a peak list of protein and peptide masses was obtained and
      compared to a known Pnc protein mass library, in which a peptide common and
      unique to cPnc isolates was tentatively identified. Information gained from this
      study will lead to the identification and validation of proteins that are
      commonly and exclusively expressed in cPnc strains which could potentially be
      used as a biomarker in the rapid diagnosis of pneumococcal conjunctivitis.

PMID- 18708516
TI  - Role of polyphosphates in microbial adaptation to extreme environments.

PMID- 18708517
TI  - Meta-analysis of experimental data concerning antimicrobial resistance gene
      transfer rates during conjugation.
AB  - This paper presents the results of a meta-analysis of published transfer rates of
      antimicrobial resistance genes. A total of 34 papers were identified, of which 28
      contained rates estimated in relation to either donor or recipient bacterial
      counts. The published rates ranged from 10(-2) to 10(-9). Generalized linear
      modeling was conducted to identify the factors influencing this variation. Highly
      significant associations between transfer frequency and both the donor (P = 1.2 x
      10(-4)) and recipient (P = 1.0 x 10(-5)) genera were found. Also significant was
      whether the donor and recipient strains were of the same genus (P = 0.023) and
      the nature of the genetic element (P = 0.0019). The type of experiment, in vivo
      or in vitro, approached statistical significance (P = 0.12). Parameter estimates
      from a general linear model were used to estimate the probability of transfer of
      antimicrobial resistance genes to potential pathogens in the intestine following
      oral ingestion. The mean logarithms of these probabilities are in the range of [
      7.0, -3.1]. These probability distributions are suitable for use in the
      quantitative assessment of the risk of transfer of antimicrobial resistance genes
      to the intestinal flora of humans and animals.

PMID- 18708518
TI  - High and low temperatures differently affect infection density and vertical
      transmission of male-killing Spiroplasma symbionts in Drosophila hosts.
AB  - We investigated the vertical transmission, reproductive phenotype, and infection
      density of a male-killing Spiroplasma symbiont in two Drosophila species under
      physiological high and low temperatures through successive host generations. In
      both the native host Drosophila nebulosa and the nonnative host Drosophila
      melanogaster, the symbiont infection and the male-killing phenotype were stably
      maintained at 25 degrees C, rapidly lost at 18 degrees C, and gradually lost at
      28 degrees C. In the nonnative host, both the high and low temperatures
      significantly suppressed the infection density of the spiroplasma. In the native
      host, by contrast, the low temperature suppressed the infection density of the
      spiroplasma whereas the high temperature had little effect on the infection
      density. These results suggested that the low temperature suppresses both the
      infection density and the vertical transmission of the spiroplasma whereas the
      high temperature suppresses the vertical transmission preferentially. The
      spiroplasma density was consistently higher in the native host than in the
      nonnative host, suggesting that the host genotype may affect the infection
      density of the symbiont. The temperature- and genotype-dependent instability of
      the symbiont infection highlights a complex genotype-by-genotype-by-environment
      interaction and may be relevant to the low infection frequencies of the male
      killing spiroplasmas in natural Drosophila populations.

PMID- 18708519
TI  - Syntrophic growth on formate: a new microbial niche in anoxic environments.
AB  - Anaerobic syntrophic associations of fermentative bacteria and methanogenic
      archaea operate at the thermodynamic limits of life. The interspecies transfer of
      electrons from formate or hydrogen as a substrate for the methanogens is key.
      Contrary requirements of syntrophs and methanogens for growth-sustaining product
      and substrate concentrations keep the formate and hydrogen concentrations low and
      within a narrow range. Since formate is a direct substrate for methanogens, a
      niche for microorganisms that grow by the conversion of formate to hydrogen plus
      bicarbonate--or vice versa--may seem unlikely. Here we report experimental
      evidence for growth on formate by syntrophic communities of (i) Moorella sp.
      strain AMP in coculture with a thermophilic hydrogen-consuming
      Methanothermobacter species and of (ii) Desulfovibrio sp. strain G11 in coculture
      with a mesophilic hydrogen consumer, Methanobrevibacter arboriphilus AZ. In pure
      culture, neither Moorella sp. strain AMP, nor Desulfovibrio sp. strain G11, nor
      the methanogens grow on formate alone. These results imply the existence of a
      previously unrecognized microbial niche in anoxic environments.

PMID- 18708520
TI  - Differential effects of temperature on natural transformation to erythromycin and
      nalidixic acid resistance in Campylobacter coli.
AB  - Campylobacter jejuni and Campylobacter coli are naturally competent, but limited
      information exists on the impact of environmental conditions on transformation.
      In this study, we investigated the impact of temperature and microaerobic versus
      aerobic atmosphere on transformation of C. coli to erythromycin and nalidixic
      acid resistance. Frequency of transformation was not significantly different
      between microaerobic (5 to 10% CO(2)) and aerobic conditions. However, C. coli
      was transformed to erythromycin resistance at a significantly higher frequency at
      42 degrees C than at 25 degrees C (P < 0.05), and few or no transformants were
      obtained at 25 degrees C. In contrast, transformation to nalidixic acid
      resistance was highly efficient at both 42 degrees C and 25 degrees C and was
      similar or, at the most, fourfold higher at 42 degrees C than at 25 degrees C.
      DNase I treatment experiments suggested that steps both prior and subsequent to
      internalization of DNA were influenced by temperature in the case of
      transformation of C. coli to erythromycin resistance. However, the moderately
      increased (fourfold) frequency of transformation to nalidixic acid resistance at
      42 degrees C compared to that at 25 degrees C was exclusively associated with
      steps prior to DNA internalization. These findings suggest that transformation to
      erythromycin resistance may be significantly more frequent in the
      gastrointestinal tract of hosts such as poultry (at 42 degrees C) than in other
      habitats characterized by lower temperatures, whereas transformation to nalidixic
      acid resistance may be highly efficient both within and outside the animal hosts.

PMID- 18708521
TI  - Real-time PCR method for detection of pathogenic Yersinia enterocolitica in food.
AB  - The current methods for the detection of pathogenic Yersinia enterocolitica
      bacteria in food are time consuming and inefficient. Therefore, we have developed
      and evaluated in-house a TaqMan probe-based real-time PCR method for the
      detection of this pathogen. The complete method comprises overnight enrichment,
      DNA extraction, and real-time PCR amplification. Also included in the method is
      an internal amplification control. The selected primer-probe set was designed to
      use a 163-bp amplicon from the chromosomally located gene ail (attachment and
      invasion locus). The selectivity of the PCR method was tested with a diverse
      range (n = 152) of related and unrelated strains, and no false-negative or false
      positive PCR results were obtained. The sensitivity of the PCR amplification was
      85 fg purified genomic DNA, equivalent to 10 cells per PCR tube. Following the
      enrichment of 10 g of various food samples (milk, minced beef, cold-smoked
      sausage, fish, and carrots), the sensitivity ranged from 0.5 to 55 CFU Y.
      enterocolitica. Good precision, robustness, and efficiency of the PCR
      amplification were also established. In addition, the method was tested on
      naturally contaminated food; in all, 18 out of 125 samples were positive for the
      ail gene. Since no conventional culture method could be used as a reference
      method, the PCR products amplified from these samples were positively verified by
      using conventional PCR and sequencing of the amplicons. A rapid and specific real
      time PCR method for the detection of pathogenic Y. enterocolitica bacteria in
      food, as presented here, provides a superior alternative to the currently
      available detection methods and makes it possible to identify the foods at risk
      for Y. enterocolitica contamination.

PMID- 18708523
TI  - Do unsaturated phosphoinositides mix with ordered phosphadidylcholine model
      membranes?
AB  - Phosphoinositides have been shown to control membrane trafficking events by
      targeting proteins to specific cellular sites, which requires a tight regulation
      of phosphoinositide generation and turnover as well as a high degree of
      compartmentalization. To shed light on the processes that lead to the formation
      of phosphoinositide-enriched microdomains, mixed monolayers of
      phosphatidylcholine and dioleoyl-phosphatidylinositol (DOPtdIns) or dioleoyl
      phosphatidylinositol-bisphosphate [DOPtdIns(4,5)P(2)] were investigated by
      isothermal area/pressure measurements, Brewster angle microscopy, and grazing
      incidence X-ray diffraction. The results are consistent with a charge-dependent
      formation of phosphatidylinositol-containing tightly packed phases. DOPtdIns is
      capable of mixing partially with condensed 1,2-distearoyl-phosphatidylcholine
      (DSPC) and of forming mixed crystals that differ significantly from those formed
      by pure DSPC. DOPtdIns(4,5)P(2) in mixtures with DSPC is, to a much larger
      extent, phase separated. The observed phase separation of the highly charged
      DOPtdIns(4,5)P(2) is presumably water stabilized by electrostatic interactions
      and hydrogen bonding. In biological systems, an enzymatic phosphorylation of
      phosphatidylinositol in mixed domains may cause their insolubility in ordered
      phosphatidylcholine areas and lead to a cooperative reorganization of the host
      lipid membrane. This strong cooperative effect underlines the important role of
      PtdIns(4,5)P(2) in signal transduction processes and suggests that the ability of
      phosphoinositides to induce or reduce long-range interactions in phospholipid
      mixtures is crucial.

PMID- 18708522
TI  - Recovery and sequence analysis of hepatitis a virus from springwater implicated
      in an outbreak of acute viral hepatitis.
AB  - An outbreak of acute hepatitis A virus in North Carolina was linked to drinking
      water from a contaminated shallow spring by phylogenetic analysis of hepatitis A
      virus (HAV) genomic sequences. Detection of HAV and fecal indicators in the water
      provided useful and timely information to assist with public health prevention
      and control measures.

PMID- 18708524
TI  - C-reactive protein enhances macrophage lipoprotein lipase expression.
AB  - High serum levels of C-reactive protein (CRP), a strong predictor of
      cardiovascular events, are documented in patients with type 2 diabetes.
      Accumulating evidence suggests that CRP could directly promote arterial damage.
      To determine the role of CRP in diabetic atherosclerosis, we examined the effect
      of CRP on the expression of macrophage lipoprotein lipase (LPL), a proatherogenic
      molecule upregulated in type 2 diabetes. Treatment of human macrophages with
      native CRP increased, in a dose- and time-dependent manner, LPL protein
      expression and secretion. Modified CRP reproduced these effects. Preincubation of
      human macrophages with antioxidants, protein kinase C (PKC), and mitogen
      activated protein kinase (MAPK) inhibitors prevented CRP-induced LPL expression.
      Exposure of human macrophages to CRP further increased intracellular reactive
      oxygen species generation, classic PKC isozymes expression, and extracellular
      signal-regulated protein kinase 1/2 phosphorylation. In CRP-treated J774
      macrophages, increased macrophage LPL mRNA levels and enhanced binding of nuclear
      proteins to the activated protein-1 (AP-1)-enhancing element were observed. These
      effects were prevented by antioxidants, as well as by PKC, MAPK, and AP-1
      inhibitors. These data show for the first time that CRP directly increases
      macrophage LPL expression and secretion. Given the predominant role of macrophage
      LPL in atherogenesis, LPL might represent a novel factor underlying the adverse
      effect of CRP on the diabetic vasculature.

PMID- 18708525
TI  - Successful choice behavior is associated with distinct and coherent network
      states in anterior cingulate cortex.
AB  - Successful decision making requires an ability to monitor contexts, actions, and
      outcomes. The anterior cingulate cortex (ACC) is thought to be critical for these
      functions, monitoring and guiding decisions especially in challenging situations
      involving conflict and errors. A number of different single-unit correlates have
      been observed in the ACC that reflect the diverse cognitive components involved.
      Yet how ACC neurons function as an integrated network is poorly understood. Here
      we show, using advanced population analysis of multiple single-unit recordings
      from the rat ACC during performance of an ecologically valid decision-making
      task, that ensembles of neurons move through different coherent and dissociable
      states as the cognitive requirements of the task change. This organization into
      distinct network patterns with respect to both firing-rate changes and
      correlations among units broke down during trials with numerous behavioral
      errors, especially at choice points of the task. These results point to an
      underlying functional organization into cell assemblies in the ACC that may
      monitor choices, outcomes, and task contexts, thus tracking the animal's
      progression through "task space."

PMID- 18708526
TI  - Replication termination mechanism as revealed by Tus-mediated polar arrest of a
      sliding helicase.
AB  - The replication terminator protein Tus of Escherichia coli promotes polar fork
      arrest at sequence-specific replication termini (Ter) by antagonizing DNA
      unwinding by the replicative helicase DnaB. Here, we report that Tus is also a
      polar antitranslocase. We have used this activity as a tool to uncouple helicase
      arrest at a Tus-Ter complex from DNA unwinding and have shown that helicase
      arrest occurred without the generation of a DNA fork or a bubble of unpaired
      bases at the Tus-Ter complex. A mutant form of Tus, which reduces DnaB-Tus
      interaction but not the binding affinity of Tus for Ter DNA, was also defective
      in arresting a sliding DnaB. A model of polar fork arrest that proposes melting
      of the Tus-Ter complex and flipping of a conserved C residue of Ter at the
      blocking but not the nonblocking face has been reported. The model suggests that
      enhanced stability of Tus-Ter interaction caused by DNA melting and capture of a
      flipped base by Tus generates polarity strictly by enhanced protein-DNA
      interaction. In contrast, the observations presented here show that polarity of
      helicase and fork arrest in vitro is generated by a mechanism that not only
      involves interaction between the terminator protein and the arrested enzyme but
      also of Tus with Ter DNA, without any melting and base flipping in the
      termination complex.

PMID- 18708527
TI  - Evaluating and optimizing computational protein design force fields using fixed
      composition-based negative design.
AB  - An accurate force field is essential to computational protein design and protein
      fold prediction studies. Proper force field tuning is problematic, however, due
      in part to the incomplete modeling of the unfolded state. Here, we evaluate and
      optimize a protein design force field by constraining the amino acid composition
      of the designed sequences to that of a well behaved model protein. According to
      the random energy model, unfolded state energies are dependent only on amino acid
      composition and not the specific arrangement of amino acids. Therefore, energy
      discrepancies between computational predictions and experimental results, for
      sequences of identical composition, can be directly attributed to flaws in the
      force field's ability to properly account for folded state sequence energies.
      This aspect of fixed composition design allows for force field optimization by
      focusing solely on the interactions in the folded state. Several rounds of fixed
      composition optimization of the 56-residue beta1 domain of protein G yielded
      force field parameters with significantly greater predictive power: Optimized
      sequences exhibited higher wild-type sequence identity in critical regions of the
      structure, and the wild-type sequence showed an improved Z-score. Experimental
      studies revealed a designed 24-fold mutant to be stably folded with a melting
      temperature similar to that of the wild-type protein. Sequence designs using
      engrailed homeodomain as a scaffold produced similar results, suggesting the
      tuned force field parameters were not specific to protein G.

PMID- 18708528
TI  - Projected sustainability of innovative social programs.
AB  - This study is an exploratory examination of the projected sustainability of more
      than 100 projects funded by the Australian government. Using data collected by
      the body that evaluated the projects and data from a government database, it
      examines the predictors of various forms of sustainability. Findings show that
      some two thirds of the project leaders who expected their programs to continue
      after the expiration of the initial funding expected them to continue with the
      same activities and target population; almost half envisioned them diversifying
      to new activities, target groups, or locations. Auspice organization involvement
      increased the expectation that the project would be continued, project
      effectiveness decreased that expectation, and diversity of initial funding became
      less important as other sources of support and sustainability were taken into
      consideration.

PMID- 18708529
TI  - Identification of serine 205 as a site of phosphorylation on Pax3 in
      proliferating but not differentiating primary myoblasts.
AB  - Pax3, a member of the paired class homeodomain family of transcription factors,
      is essential for early skeletal muscle development. Previously, others and we
      have shown that the stability of Pax3 is regulated on a post-translational level.
      Evidence in the literature and from our laboratory suggests that phosphorylation,
      a common form of regulation, may play a role. However, at present, the sites of
      Pax3 phosphorylation are not known. We demonstrate here the first evidence that
      Pax3 exists as a phosphoprotein in proliferating mouse primary myoblasts. Using
      an in vitro kinase assay, deletion, and point mutant analysis, we conclusively
      identify Ser205 as a site of phosphorylation. The phosphorylation of Ser205 on
      endogenously expressed Pax3 was confirmed in vivo using antibodies specific for
      phosphorylation at Ser205. Finally, we demonstrate for the first time that the
      phosphorylation status of endogenous Pax3 changes rapidly upon the induction of
      myogenic differentiation. The presence of phosphorylation in a region of Pax3
      important for mediating protein-protein interactions, and the fact that
      phosphorylation is lost upon induction of differentiation, allow for speculation
      on the biological relevance of phosphorylation.

PMID- 18708530
TI  - Measuring immunization coverage: what best reflects the protection of children?

PMID- 18708531
TI  - Antiretroviral therapy-induced functional modification of IgG4 and IgM responses
      in HIV-1-infected individuals screened by an allosteric biosensor.
AB  - We have explored the effect of antiretroviral drugs on the antiviral immune
      response in human immunodeficiency virus-1 (HIV-1)-infected patients by using an
      enzymatic immunosensor that detects epitope-modifying anti-gp41 antibodies. By
      this molecular sensing approach, we have identified an irreversible impact of
      drug administration on the functionality of IgG4 and IgM specific antibodies
      regarding the structural modification promoted on their target epitope. During
      the antiretroviral therapy, the prevalent induced fit promoted by IgM on the
      epitope was lost at the expense of that promoted by IgG4, suggesting alternative
      ness in the neutralization potency of these antibody subpopulations. Because the
      particular drug composition of the antiretroviral treatment did not affect such
      immune shift, the obtained data strongly suggest that the drop in the viral load
      and the consequent lost of antigenemia are responsible for the functional
      adaptation observed in the humoral response.

PMID- 18708532
TI  - An analysis of methods to prevent peritoneal dialysis catheter infections.

PMID- 18708533
TI  - Should older patients be offered peritoneal dialysis?
AB  - On haemodialysis, my life was not my own - handing control to nursing staff for 4
      hours, 3 days a week, surrounded by noisy machines and unhappy patients,
      returning home after 11 hours, too exhausted to eat and falling into bed.
      However, peritoneal dialysis has given me back my life. I am in control of me and
      am treated like a human being, not just a patient. There are minor drawbacks,
      such as storage for the fluids and being unable to have a bath, but it is a small
      price to pay.

PMID- 18708534
TI  - The elderly patient on CAPD: helping patients cope with peritoneal dialysis.

PMID- 18708535
TI  - Is the decline of peritoneal dialysis in the elderly a breakdown in the process
      of care?

PMID- 18708536
TI  - Peritonitis risk for older patients on peritoneal dialysis.

PMID- 18708537
TI  - Assisted peritoneal dialysis: also for the late referred elderly patient.

PMID- 18708538
TI  - A comparison of outcomes between diabetic and nondiabetic CAPD patients in India.
AB  - BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) has been an
      established modality of renal replacement therapy in India for a decade, but
      there is a paucity of published data on the outcome of CAPD patients in India. We
      analyzed our data to determine the overall predictors of survival and compared
      patient survival between diabetic and nondiabetic end-stage renal disease
      patients on CAPD. METHODS: Of 373 patients, 197 were diabetic (165 males, 32
      females) and 176 nondiabetic (104 males, 72 females). Patients were followed for
      22 +/- 14 patient-months. Patients were prospectively followed until the study
      end point or death. RESULTS: Overall median survival was 48 patient-months.
      Median survival of diabetics (34.5 patient-months) was significantly inferior to
      nondiabetic patients (59 patient-months) p = 0.001. Overall patient survival at
      1, 2, 3, 4, and 5 years was 90%, 72%, 60%, 49%, and 39%, respectively. Patient
      survival of diabetics versus nondiabetics at 1, 2, 3, 4, and 5 years was 85%
      versus 96%, 62% vs 82%, 48% vs 72%, 39% vs 62%, and 34% vs 42%, respectively. The
      relative risk of mortality in nondiabetics (34/176) was less than that in
      diabetic patients (71/197): odds ratio (OR) 0.43, 95% confidence interval (CI)
      0.26 - 0.68; p = 0.001. On Cox regression analysis, diabetes (OR 1.95, 95% CI
      1.23 - 3.07; p = 0.004), comorbidities (OR 0.39, 95% CI 0.25 - 0.61; p = 0.001),
      peritonitis (OR 1.79, 95% CI 1.19 - 2.68; p = 0.005), malnutrition (OR 0.52, 95%
      CI 0.29 - 0.94; p = 0.03), and residual glomerular filtration rate at initiation
      of CAPD (OR 0.87, 95% CI 0.81 - 0.93; p = 0.001) were significant predictors of
      overall mortality. Age (OR 0.68, 95% CI 0.45 - 1.03; p = 0.07), gender (OR 0.66,
      95% CI 0.42 - 1.03; p = 0.06), and albumin level at initiation of CAPD (OR 0.92,
      95% CI 0.64 - 1.33; p = 0.68) were not predictors of mortality. Age (56 +/- 10 vs
      46 +/- 15 years, p = 0.001), comorbidities (51/197 vs 16/176, p = 0.001),
      peritonitis rate (0.68 vs 0.50 episodes/patient-year, p = 0.056), and severe
      malnutrition (27/197 vs 10/176, p = 0.002) were higher in diabetic than in
      nondiabetic patients. CONCLUSION: In India the majority of CAPD patients are
      diabetic. Patient survival was inferior in diabetic compared to nondiabetic
      patients on CAPD, but survival was statistically similar after adjustment for
      comorbidities. Diabetes, comorbidities, residual glomerular filtration rate,
      peritonitis, and severe malnutrition are predictors of mortality in CAPD
      patients.

PMID- 18708539
TI  - Piece by piece: solving the puzzle of peritoneal fibrosis.

PMID- 18708540
TI  - Theory and reality in the selection of peritoneal dialysis.

PMID- 18708541
TI  - Is intermittent peritoneal dialysis still a valid treatment option?

PMID- 18708542
TI  - A pyruvate-buffered dialysis fluid induces less peritoneal angiogenesis and
      fibrosis than a conventional solution.
AB  - BACKGROUND: Conventional lactate-buffered peritoneal dialysis (PD) fluids
      containing glucose and glucose degradation products are believed to contribute to
      the development of fibrosis and angiogenesis in the dialyzed peritoneum. To
      reduce potential negative effects of lactate, pyruvate was substituted as a
      buffer and its effects on peritoneal pathological alterations were studied in a
      chronic peritoneal exposure model in the rat. METHODS: 20 Wistar rats were
      infused intraperitoneally with pyruvate-buffered (n = 9) or lactate-buffered PD
      fluid. After 20 weeks of daily infusion, peritoneal function was assessed. In
      omental peritoneal tissue, the number of blood vessels was analyzed following
      alpha-smooth muscle actin staining. The degree of fibrosis was quantitated in
      Picro Sirius Red-stained sections and by assessment of the hydroxyproline
      content. Plasma lactate/pyruvate and betahydroxybutyrate/acetoacetate (BBA/AA)
      ratios were determined. Plasma and dialysate vascular endothelial growth factor
      (VEGF) levels were quantitated by ELISA. RESULTS: The mass transfer area
      coefficient of creatinine was higher and the dialysate-to-plasma ratio of sodium
      was lower in pyruvate-treated animals compared to the lactate-treated group (0.11
      vs 0.05 mL/min, p < 0.05, and 78% vs 89%, p < 0.05). The BBA/AA ratio tended to
      be lower in the pyruvate animals (p = 0.07). The number of blood vessels was
      lower in pyruvate-treated animals (16 vs 37 per field, p < 0.001). Total surface
      area, luminal area, and wall/total area of the vessels were larger in the
      pyruvate group. The degree of fibrosis was lower in intersegmental and
      perivascular areas of pyruvate-exposed animals. Effluent VEGF was higher in the
      pyruvate group. CONCLUSIONS: Replacement of lactate by pyruvate resulted in
      changes in peritoneal solute transport, accompanied by a reduction in both
      peritoneal membrane angiogenesis and fibrosis, suggesting potentially novel
      mechanisms to reduce glucose-driven alterations to the peritoneal membrane in PD
      patients.

PMID- 18708543
TI  - Vascular endothelial growth factor expression in peritoneal mesothelial cells
      undergoing transdifferentiation.
AB  - OBJECTIVE: To analyze gene expression of localized peritoneal tissue structures
      in a rodent model of peritoneal fibrosis. METHODS: Female Sprague Dawley rats
      were treated with an intraperitoneal injection of an adenovirus expressing active
      transforming growth factor-beta or control adenovirus. Four and 7 days after
      infection, animals were sacrificed and frozen sections of parietal peritoneum
      were subjected to immunofluorescence-aided laser capture microdissection in order
      to isolate vascular, mesothelial, and submesothelial structures. RNA was
      extracted from microdissected tissue and gene expression was analyzed by
      quantitative reverse-transcript polymerase chain reaction. We analyzed genes
      involved in angiogenesis, epithelial-to-mesenchymal transdifferentiation, and
      fibrosis. Vascular endothelial growth factor and alpha-smooth muscle actin
      expression was analyzed with immunohistochemistry of formalin-fixed tissue.
      RESULTS: Transforming growth factor-beta(1) induced expression of Snail and alpha
      smooth muscle actin genes in the peritoneal mesothelium. This same cell
      population also demonstrated increased gene expression of vascular endothelial
      growth factor. The distribution of this growth factor was confirmed by
      immunohistochemistry. The fibrogenic growth factor, connective tissue growth
      factor, was also strongly induced in the peritoneal mesothelium. CONCLUSIONS:
      Using immunofluorescence-aided laser capture microdissection, we were able to
      study gene expression in subcompartments of the peritoneal tissue. We
      demonstrated that mesothelial cells exhibiting mesenchymal transdifferentiation
      are associated with increased expression of genes associated with fibrosis and
      angiogenesis.

PMID- 18708544
TI  - A prospective study of the efficacy of local application of gentamicin versus
      mupirocin in the prevention of peritoneal dialysis catheter-related infections.
AB  - BACKGROUND: Peritoneal dialysis (PD)-related infections are the major cause of
      technique failure. Exit-site infections (ESI) can be prevented by local
      application of antibiotics. Mupirocin (M) is the most extensively studied drug
      for this application. Long-term use can result in the development of resistance.
      Gentamicin (G) is an attractive alternative, with both gram-positive and gram
      negative activities. We studied the comparative efficacy of G cream versus M
      ointment in the prevention of PD-related infections in a Chinese cohort. METHODS:
      This was a prospective study of adult PD patients of the Princess Margaret
      Hospital, Hong Kong. Patients were excluded if they had active infection, recent
      ESI or peritontiis, history of allergy to either drug, or were unable to apply
      the drug or give consent. Patients were taught to apply the drug daily to the
      exit site after routine exitsite care. Records were tracked prospectively during
      hospital admissions and clinic follow-ups. RESULTS: 95 patients were recruited;
      14 discontinued the study. The ESI rates were 0.38 and 0.20 episodes/patient-year
      for the G group and the M group respectively (p = 0.36). Gram-positive ESI rates
      were 0.18 and 0 episodes/patient-year for the G group and the M group
      respectively. Gram-negative ESI rates were 0.20 episodes/patient-year for both
      groups (p = 0.62). The overall peritonitis rates were similar in the two groups
      (p = 0.91). DISCUSSION: In addition to good perioperative care and strict exit
      site care, local antibiotic application can prevent ESI. Mupirocin has been
      extensively studied and shown to be effective. Similar if not superior effects of
      G cream have been demonstrated. In this study, neither antibiotic gave
      significantly better results in the prevention of either ESI or peritonitis.
      CONCLUSIONS: Both gentamicin and mupirocin were effective as prophylaxis for ESI.
      Longer study is required to determine the long-term efficacy and the potential
      beneficial effect on the prevention of peritonitis.

PMID- 18708545
TI  - Variability in case mix and peritoneal dialysis selection in fifty-nine French
      districts.
AB  - In France, the use of peritoneal dialysis (PD) as the first-choice treatment
      varies greatly between districts, as it is already known to do between countries.
      Baseline clinical factors associated with choice of first modality were analyzed
      in 10 815 new end-stage renal disease patients in 59 districts. To describe
      practices at the district level, we used an agglomerative hierarchical
      classification, with proximity defined by a likelihood-ratio test that compared
      multivariate logistic regressions of the following factors: age, gender,
      diabetes, congestive heart failure, severe behavioral disorders, mobility, and
      employment. To propose a typology, each cluster of districts was described by a
      multivariate logistic regression. While populations starting PD in France, as
      elsewhere, are more likely to be young or employed, they are also more likely to
      be elderly or have congestive heart failure or severe behavioral disorders.
      Overall, 14% of patients start with PD, but this rate varies significantly across
      districts, from 0% to 45%. A specific combination of factors was associated with
      the first-choice modality in each group of districts. This study highlights the
      lack of consensual medical criteria for this choice and the likelihood that
      nonmedical factors may explain the observed differences. The high variability
      suggests that PD can be used in almost all clinical conditions. Accordingly,
      patient preference should play a more important role in the decision-making
      process.

PMID- 18708546
TI  - In-center intermittent peritoneal dialysis: retrospective ten-year single-center
      experience with thirty consecutive patients.
AB  - BACKGROUND: In-center intermittent peritoneal dialysis (IPD) is sometimes
      performed in elderly and multimorbid patients that have failed hemodialysis and
      that are unable to perform peritoneal dialysis (PD) at home. Complications,
      frequency of hospital admission, and survival are often claimed to be dismal
      although current data are lacking. METHODS: We performed a retrospective cohort
      study of patients that underwent IPD at Hannover Medical School, Germany, between
      1997 and 2007. Underlying renal disorders, comorbidity, and circumstances that
      precluded hemodialysis and home PD were recorded. Survival, cause of death,
      episodes of hospitalization, and episodes of peritonitis were calculated.
      Laboratory values at baseline and after 3 months of IPD were also retrieved.
      RESULTS: We identified 30 patients with severe comorbidity (median Charlson
      Comorbidity Index of 6; n = 30) who underwent IPD for 439 months in total. The
      majority of patients had vascular/hypertensive nephropathy (n = 12; 40%);
      congestive heart failure was the leading cause for choosing PD (n = 13; 43.3%);
      73.3% of our patients had either no partner or at least one disease that
      precluded home therapy. Hospitalization rate was 1.39 admissions per patient-year
      and there was 1 episode of peritonitis per 48.8 IPD-months. Mean survival was
      26.6 months (median 17 months; n = 30); sepsis was the leading cause of death (n
      = 13; 59.1%). CONCLUSIONS: IPD is associated with fewer episodes of peritonitis,
      fewer admissions, and longer survival than is often believed. Suitable patients
      in whom palliative care alone seems inappropriate should not be denied a trial of
      IPD if they so choose.

PMID- 18708547
TI  - Concentration of adipokines in peritoneal effluent: a new marker of acute
      peritonitis in peritoneal dialysis patients?
AB  - BACKGROUND: An early and reliable diagnostic procedure for acute peritonitis in
      patients on peritoneal dialysis (PD) without typical clinical symptoms remains an
      important challenge in modern nephrology. During the first days of peritonitis,
      establishing the diagnosis based on peritoneal effluent pleocytosis and
      inflammatory markers [C-reactive protein (CRP) or interleukin-6] is not efficient
      in all cases. Increased peritoneal membrane permeability is a well-known
      consequence of peritonitis. Therefore, we evaluated the concentrations of
      selected circulating adipose tissue-derived proteins in the peritoneal effluent
      of PD patients with episodes of acute peritonitis. MATERIAL AND METHODS:
      Concentrations of adiponectin and leptin, in both plasma and peritoneal effluent,
      were assessed in 24 adult PD patients with peritonitis episodes confirmed by
      clinical symptoms and/or microbiological tests, and in 23 PD patients without
      signs and symptoms of inflammation (control group). RESULTS: In peritoneal
      effluent collected from patients with acute peritonitis (also without pleocytosis
      or increased CRP), both adiponectin and leptin concentrations were markedly
      elevated: adiponectin 744.1 (344.2 - 1144.1) ng/mL vs 4.8 (3.1 - 6.5) ng/mL;
      leptin 16.3 (9.4 - 23.1) ng/mL vs 5.1 (0.5 - 9.6) ng/mL. Receiver operating
      characteristic analyses revealed that peritoneal effluent adiponectin
      concentration >180 ng/mL has 100% sensitivity and 100% specificity, while
      peritoneal effluent leptin concentration >11.0 ng/mL has 58.3% sensitivity and
      95.5% specificity for the diagnosis of acute peritonitis. The increases in
      adiponectin and leptin concentrations in peritoneal effluent were not
      consequences of changes in their plasma levels. A positive correlation between
      peritoneal effluent and plasma concentrations of adiponectin and leptin in
      patients with peritonitis was found. CONCLUSION: Increased concentration of
      leptin and especially adiponectin in peritoneal effluent seems to be a valuable
      and new early marker of high peritoneal membrane permeability due to acute
      peritonitis.

PMID- 18708548
TI  - Daily remote peritoneal dialysis monitoring: an adjunct to enhance patient care.
AB  - Peritoneal dialysis (PD) is the preferred dialysis modality in children, but it
      relies on the patient or caregiver to perform dialysis daily at home. We describe
      the utilization of a modem transmission system in 2 pediatric PD patients to
      improve communication with the dialysis team, monitor compliance via frequent
      remote data collection, and decrease dialysis-related complications. A home
      dialysis modem was provided for each patient and connected to the home telephone
      line by the dialysis nurse. PD treatment data were transmitted daily to the
      dialysis unit, records entered into the patient's electronic medical record, and
      reviewed by the patient's PD nurse and/or pediatric nephrologist and adjustments
      made accordingly. This resulted in improved medical outcomes specifically related
      to fluid balance and cardiovascular health, ultimately facilitating renal
      transplantation in each case. In summary, the use of the ProCard (Baxter
      Healthcare, Deerfield, Illinois, USA) has improved the ability to monitor home PD
      patients effectively. However, the additional use of the modem to transmit data
      on a more frequent basis can further enhance the care of chronic continuous
      cycling PD patients and should be considered in more challenging medical
      situations.

PMID- 18708549
TI  - Effect of prostaglandin E1 on peritoneal membrane transport in CAPD-treated
      diabetic patients.

PMID- 18708550
TI  - Ampicillin-sulbactam and amikacin used as second-line antibiotics for patients
      with culture-negative peritonitis.

PMID- 18708551
TI  - Comparative study of adequacy of dialysis and health-related quality of life in
      patients on CAPD and APD.

PMID- 18708552
TI  - Nocardia peritonitis -- a case report and literature review.

PMID- 18708553
TI  - Sphingomonas paucimobilis peritonitis: a case report and literature review.

PMID- 18708554
TI  - Minilaparotomy with manual correction for malfunctioning peritoneal dialysis
      catheters.

PMID- 18708555
TI  - Spontaneous peritoneal membrane rupture with extravasation of peritoneal fluid
      into the lower limbs and flank in a peritoneal dialysis patient.

PMID- 18708556
TI  - Chronic peritoneal dialysis treatment in a pediatric patient with Down syndrome.

PMID- 18708557
TI  - Management of patients with recurrent nephrosis and intractable edema by
      intraperitoneal instillation of icodextrin solution.

PMID- 18708558
TI  - Cloudy dialysate and pseudomembranous colitis in a patient on CAPD.

PMID- 18708559
TI  - "Icodextrin alone" for initiation of peritoneal dialysis.

PMID- 18708560
TI  - Effect of vitamin D supplementation on calcidiol and parathyroid hormone levels.

PMID- 18708561
TI  - Transcriptome for photobiological hydrogen production induced by sulfur
      deprivation in the green alga Chlamydomonas reinhardtii.
AB  - Photobiological hydrogen production using microalgae is being developed into a
      promising clean fuel stream for the future. In this study, microarray analyses
      were used to obtain global expression profiles of mRNA abundance in the green
      alga Chlamydomonas reinhardtii at different time points before the onset and
      during the course of sulfur-depleted hydrogen production. These studies were
      followed by real-time quantitative reverse transcription-PCR and protein
      analyses. The present work provides new insights into photosynthesis, sulfur
      acquisition strategies, and carbon metabolism-related gene expression during
      sulfur-induced hydrogen production. A general trend toward repression of
      transcripts encoding photosynthetic genes was observed. In contrast to all other
      LHCBM genes, the abundance of the LHCBM9 transcript (encoding a major light
      harvesting polypeptide) and its protein was strongly elevated throughout the
      experiment. This suggests a major remodeling of the photosystem II light
      harvesting complex as well as an important function of LHCBM9 under sulfur
      starvation and photobiological hydrogen production. This paper presents the first
      global transcriptional analysis of C. reinhardtii before, during, and after
      photobiological hydrogen production under sulfur deprivation.

PMID- 18708562
TI  - Identification of the putative protein phosphatase gene PTC1 as a virulence
      related gene using a silkworm model of Candida albicans infection.
AB  - Protein phosphatases are critical for the regulation of many cellular processes.
      Null mutants of 21 putative protein phosphatases of Candida albicans were
      constructed by consecutive allele replacement using the URA3 and ARG4 marker
      genes. A simple silkworm model of C. albicans infection was used to screen the
      panel of mutants. Four null mutant (cmp1Delta, yvh1Delta, sit4Delta, and
      ptc1Delta) strains showed attenuated virulence in the silkworm model relative to
      that of control and parental strains. Three of the mutants, the cmp1Delta,
      yvh1Delta, and sit4Delta mutants, had previously been identified as affecting
      virulence in a conventional mouse model, indicating the validity of the silkworm
      model screen. Disruption of the putative protein phosphatase gene PTC1 of C.
      albicans, which has 52% identity to the Saccharomyces cerevisiae type 2C protein
      phosphatase PTC1, significantly reduced virulence in the silkworm model. The
      mutant was also avirulent in a mouse model of disseminated candidiasis.
      Reintroducing either of the C. albicans PTC1 alleles into the disruptant strain,
      using a cassette containing either allele under the control of a constitutive
      ACT1 promoter, restored virulence in both infection models. Characterization of
      ptc1Delta revealed other phenotypic traits, including reduced hyphal growth in
      vitro and in vivo, and reduced extracellular proteolytic activity. We conclude
      that PTC1 may contribute to pathogenicity in C. albicans.

PMID- 18708563
TI  - Anoxia-induced suspended animation in budding yeast as an experimental paradigm
      for studying oxygen-regulated gene expression.
AB  - A lack of oxygen can force many organisms to enter into recoverable hypometabolic
      states. To better understand how organisms cope with oxygen deprivation, our
      laboratory previously had shown that when challenged with anoxia, both the
      nematode Caenorhabditis elegans and embryos of the zebrafish Danio rerio enter
      into suspended animation, in which all life processes that can be observed by
      light microscopy reversibly halt pending the restoration of oxygen (P. A. Padilla
      and M. B. Roth, Proc. Natl. Acad. Sci. USA 98:7331-7335, 2001, and P. A. Padilla,
      T. G. Nystul, R. A. Zager, A. C. Johnson, and M. B. Roth, Mol. Biol. Cell 13:1473
      1483, 2002). Here, we show that both sporulating and vegetative cells of the
      budding yeast Saccharomyces cerevisiae also enter into a similar state of
      suspended animation when made anoxic on a nonfermentable carbon source.
      Transcriptional profiling using cDNA microarrays and follow-on quantitative real
      time PCR analysis revealed a relative derepression of aerobic metabolism genes in
      carbon monoxide (CO)-induced anoxia when compared to nitrogen (N(2)) gas-induced
      anoxia, which is consistent with the known oxygen-mimetic effects of CO. We also
      found that mutants deleted for components of the mitochondrial retrograde
      signaling pathway can tolerate prolonged exposure to CO but not to N(2). We
      conclude that the cellular response to anoxia is dependent on whether the anoxic
      gas is an oxygen mimetic and that the mitochondrial retrograde signaling pathway
      is functionally important for mediating this response.

PMID- 18708564
TI  - The putative alpha-1,2-mannosyltransferase AfMnt1 of the opportunistic fungal
      pathogen Aspergillus fumigatus is required for cell wall stability and full
      virulence.
AB  - Proteins entering the eukaryotic secretory pathway commonly are glycosylated.
      Important steps in this posttranslational modification are carried out by
      mannosyltransferases. In this study, we investigated the putative alpha-1,2
      mannosyltransferase AfMnt1 of the human pathogenic mold Aspergillus fumigatus.
      AfMnt1 belongs to a family of enzymes that comprises nine members in
      Saccharomyces cerevisiae but only three in A. fumigatus. A Deltaafmnt1 mutant is
      viable and grows normally at 37 degrees C, but its hyphal cell wall appears to be
      thinner than that of the parental strain. The lack of AfMnt1 leads to a higher
      sensitivity to calcofluor white and Congo red but not to sodium dodecyl sulfate.
      The growth of the mutant is abrogated at 48 degrees C but can be restored by
      osmotic stabilization. The resulting colonies remain white due to a defect in the
      formation of conidia. Electron and immunofluorescence microscopy further revealed
      that the observed growth defect of the mutant at 48 degrees C can be attributed
      to cell wall instability resulting in leakage at the hyphal tips. Using a red
      fluorescence fusion protein, we localized AfMnt1 in compact, brefeldin A
      sensitive organelles that most likely represent fungal Golgi equivalents. The
      tumor necrosis factor alpha response of murine macrophages to hyphae was not
      affected by the lack of the afmnt1 gene, but the corresponding mutant was
      attenuated in a mouse model of infection. This and the increased sensitivity of
      the Deltaafmnt1 mutant to azoles, antifungal agents that currently are used to
      treat Aspergillus infections, suggest that alpha-1,2-mannosyltransferases are
      interesting targets for novel antifungal drugs.

PMID- 18708565
TI  - Late onset depressive symptoms can be a marker of cerebral vascular pathology.

PMID- 18708566
TI  - Treatment of neurocysticercosis: a randomised controlled trial.

PMID- 18708567
TI  - Neurological picture. Bilateral idiopathic hypertrophy of the first dorsal
      interosseous muscles in a 43-year-old man.

PMID- 18708568
TI  - Neurological picture. Fluorotic cervical myelopathy.

PMID- 18708569
TI  - Testicular teratoma and anti-N-methyl-D-aspartate receptor-associated
      encephalitis.

PMID- 18708570
TI  - Dyspnoea due to vocal fold abduction paresis in anti-MuSK myasthenia gravis.

PMID- 18708571
TI  - Neuromyelitis optica in patients with gluten sensitivity associated with
      antibodies to aquaporin-4.

PMID- 18708572
TI  - DPP6 gene variability confers increased risk of developing sporadic amyotrophic
      lateral sclerosis in Italian patients.

PMID- 18708574
TI  - Plant hormone receptors: new perceptions.
AB  - Plant growth and development require the integration of a variety of
      environmental and endogenous signals that, together with the intrinsic genetic
      program, determine plant form. Central to this process are several growth
      regulators known as plant hormones or phytohormones. Despite decades of study,
      only recently have receptors for several of these hormones been identified,
      revealing novel mechanisms for perceiving chemical signals and providing plant
      biologists with a much clearer picture of hormonal control of growth and
      development.

PMID- 18708576
TI  - Noncyclic Notch activity in the presomitic mesoderm demonstrates uncoupling of
      somite compartmentalization and boundary formation.
AB  - To test the significance of cyclic Notch activity for somite formation in mice,
      we analyzed embryos expressing activated Notch (NICD) throughout the presomitic
      mesoderm (PSM). Embryos expressing NICD formed up to 18 somites. Expression in
      the PSM of Hes7, Lfng, and Spry2 was no longer cyclic, whereas Axin2 was
      expressed dynamically. NICD expression led to caudalization of somites, and loss
      of Notch activity to their rostralization. Thus, segmentation and anterior
      posterior somite patterning can be uncoupled, differential Notch signaling is not
      required to form segment borders, and Notch is unlikely to be the pacemaker of
      the segmentation clock.

PMID- 18708575
TI  - C. elegans dauer formation and the molecular basis of plasticity.
AB  - Because life is often unpredictable, dynamic, and complex, all animals have
      evolved remarkable abilities to cope with changes in their external environment
      and internal physiology. This regulatory plasticity leads to shifts in behavior
      and metabolism, as well as to changes in development, growth, and reproduction,
      which is thought to improve the chances of survival and reproductive success. In
      favorable environments, the nematode Caenorhabditis elegans develops rapidly to
      reproductive maturity, but in adverse environments, animals arrest at the dauer
      diapause, a long-lived stress resistant stage. A molecular and genetic analysis
      of dauer formation has revealed key insights into how sensory and dietary cues
      are coupled to conserved endocrine pathways, including insulin/IGF, TGF-beta,
      serotonergic, and steroid hormone signal transduction, which govern the choice
      between reproduction and survival. These and other pathways reveal a molecular
      basis for metazoan plasticity in response to extrinsic and intrinsic signals.

PMID- 18708577
TI  - Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are
      cooperative oncogenic events.
AB  - The mammalian target of rapamycin (mTOR) represents a critical signaling
      crossroad where pathways commonly disrupted in cancer converge. We report here
      that Rheb GTPase, the upstream activator of the mTOR complex 1 (mTORC1) is
      amplified in human prostate cancers. We demonstrate that Rheb overexpression
      promotes hyperplasia and a low-grade neoplastic phenotype in the mouse prostate
      while eliciting a concomitant senescence response and a negative feedback loop
      limiting Akt activation. Importantly, we show that Pten haploinsufficiency
      cooperates with Rheb overexpression to markedly promote prostate tumorigenesis.
      We conclude that Rheb acts as a proto-oncogene in the appropriate genetic milieu
      and signaling context.

PMID- 18708578
TI  - Tumorigenic activity and therapeutic inhibition of Rheb GTPase.
AB  - The AKT-mTOR pathway harbors several known and putative oncogenes and tumor
      suppressors. In a phenotypic screen for lymphomagenesis, we tested candidate
      genes acting upstream of and downstream from mTOR in vivo. We find that Rheb, a
      proximal activator of mTORC1, can produce rapid development of aggressive and
      drug-resistant lymphomas. Rheb causes mTORC1-dependent effects on apoptosis,
      senescence, and treatment responses that resemble those of Akt. Moreover, Rheb
      activity toward mTORC1 requires farnesylation and is readily blocked by a
      pharmacological inhibitor of farnesyltransferase (FTI). In Pten-deficient tumor
      cells, inhibition of Rheb by FTI is responsible for the drug's anti-tumor
      effects, such that a farnesylation-independent mutant of Rheb renders these
      tumors resistant to FTI therapy. Notably, RHEB is highly expressed in some human
      lymphomas, resulting in mTORC1 activation and increased sensitivity to rapamycin
      and FTI. Downstream from mTOR, we examined translation initiation factors that
      have been implicated in transformation in vitro. Of these, only eIF4E was able to
      enhance lymphomagenesis in vivo. In summary, the Rheb GTPase is an oncogenic
      activity upstream of mTORC1 and eIF4E and a direct therapeutic target of
      farnesyltransferase inhibitors in cancer.

PMID- 18708579
TI  - Clustering of yeast tRNA genes is mediated by specific association of condensin
      with tRNA gene transcription complexes.
AB  - The 274 tRNA genes in Saccharomyces cerevisiae are scattered throughout the
      linear maps of the 16 chromosomes, but the genes are clustered at the nucleolus
      when compacted in the nucleus. This clustering is dependent on intact nucleolar
      organization and contributes to tRNA gene-mediated (tgm) silencing of RNA
      polymerase II transcription near tRNA genes. After examination of the
      localization mechanism, we find that the chromosome-condensing complex,
      condensin, is involved in the clustering of tRNA genes. Conditionally defective
      mutations in all five subunits of condensin, which we confirm is bound to active
      tRNA genes in the yeast genome, lead to loss of both pol II transcriptional
      silencing near tRNA genes and nucleolar clustering of the genes. Furthermore, we
      show that condensin physically associates with a subcomplex of RNA polymerase III
      transcription factors on the tRNA genes. Clustering of tRNA genes by condensin
      appears to be a separate mechanism from their nucleolar localization, as
      microtubule disruption releases tRNA gene clusters from the nucleolus, but does
      not disperse the clusters. These observations suggest a widespread role for
      condensin in gene organization and packaging of the interphase yeast nucleus.

PMID- 18708580
TI  - Identification of cis-acting sites for condensin loading onto budding yeast
      chromosomes.
AB  - Eukaryotic chromosomes reach their stable rod-shaped appearance in mitosis in a
      reaction dependent on the evolutionarily conserved condensin complex. Little is
      known about how and where condensin associates with chromosomes. Here, we analyze
      condensin binding to budding yeast chromosomes using high-resolution
      oligonucleotide tiling arrays. Condensin-binding sites coincide with those of the
      loading factor Scc2/4 of the related cohesin complex. The sites map to tRNA and
      other genes bound by the RNA polymerase III transcription factor TFIIIC, and
      ribosomal protein and SNR genes. An ectopic B-box element, recognized by TFIIIC,
      constitutes a minimal condensin-binding site, and TFIIIC and the Scc2/4 complex
      promote functional condensin association with chromosomes. A similar pattern of
      condensin binding is conserved along fission yeast chromosomes. This reveals that
      TFIIIC-binding sites, including tRNA genes, constitute a hitherto unknown
      chromosomal feature with important implications for chromosome architecture
      during both interphase and mitosis.

PMID- 18708581
TI  - Study of an RNA helicase implicates small RNA-noncoding RNA interactions in
      programmed DNA elimination in Tetrahymena.
AB  - Tetrahymena eliminates micronuclear-limited sequences from the developing
      macronucleus during sexual reproduction. Homology between the sequences to be
      eliminated and approximately 28-nucleotide small RNAs (scnRNAs) associated with
      an Argonaute family protein Twi1p likely underlies this elimination process.
      However, the mechanism by which Twi1p-scnRNA complexes identify micronuclear
      limited sequences is not well understood. We show that a Twi1p-associated
      putative RNA helicase Ema1p is required for the interaction between Twi1p and
      chromatin. This requirement explains the phenotypes of EMA1 KO strains, including
      loss of selective down-regulation of scnRNAs homologous to macronuclear-destined
      sequences, loss of H3K9 and K27 methylation in the developing new macronucleus,
      and failure to eliminate DNA. We further demonstrate that Twi1p interacts with
      noncoding transcripts derived from parental and developing macronuclei and this
      interaction is greatly reduced in the absence of Ema1p. We propose that Ema1p
      functions in DNA elimination by stimulating base-pairing interactions between
      scnRNAs and noncoding transcripts in both parental and developing new
      macronuclei.

PMID- 18708582
TI  - Genetic identification of yeast 18S rRNA residues required for efficient
      recruitment of initiator tRNA(Met) and AUG selection.
AB  - High-resolution structures of bacterial 70S ribosomes have provided atomic
      details about mRNA and tRNA binding to the decoding center during elongation, but
      such information is lacking for preinitiation complexes (PICs). We identified
      residues in yeast 18S rRNA critical in vivo for recruiting methionyl tRNA(i)(Met)
      to 40S subunits during initiation by isolating mutations that derepress GCN4 mRNA
      translation. Several such Gcd(-) mutations alter the A928:U1389 base pair in
      helix 28 (h28) and allow PICs to scan through the start codons of upstream ORFs
      that normally repress GCN4 translation. The A928U substitution also impairs TC
      binding to PICs in a reconstituted system in vitro. Mutation of the bulge G926 in
      h28 and certain other residues corresponding to direct contacts with the P-site
      codon or tRNA in bacterial 70S complexes confer Gcd(-) phenotypes that (like A928
      substitutions) are suppressed by overexpressing tRNA(i)(Met). Hence, the
      nonconserved 928:1389 base pair in h28, plus conserved 18S rRNA residues
      corresponding to P-site contacts in bacterial ribosomes, are critical for
      efficient Met-tRNA(i)(Met) binding and AUG selection in eukaryotes.

PMID- 18708583
TI  - Regulation of apoptosis by XIAP ubiquitin-ligase activity.
AB  - Inhibitor of Apoptosis Proteins (IAPs) can bind to and inhibit caspases, the key
      executioners of apoptosis. Because IAPs are frequently overexpressed in human
      tumors, they have become major pharmacological targets for developing new cancer
      therapeutics. However, the precise physiological function of individual mammalian
      IAPs and their role as E3 ubiquitin-ligases in situ remain largely obscure. Here,
      we investigated the function of XIAP ubiquitin-ligase activity by inactivating
      the RING motif via gene targeting in the mouse. Removing the RING stabilized XIAP
      in apoptotic thymocytes, demonstrating that XIAP ubiquitin-ligase activity is a
      major determinant of XIAP protein stability. Surprisingly, the increased amounts
      of "XIAP-BIR-only" protein did not lead to attenuated but rather increased
      caspase activity and apoptosis. DeltaRING embryonic stem cells and fibroblasts
      had elevated caspase-3 enzyme activity, and XIAP DeltaRING embryonic fibroblasts
      were strongly sensitized to TNF-alpha-induced apoptosis. Similar results were
      obtained with XIAP deficient mice. Furthermore, deletion of the RING also
      improved the survival of mice in the Emu-Myc lymphoma model. This demonstrates a
      physiological requirement of XIAP ubiquitin-ligase activity for the inhibition of
      caspases and for tumor suppression in vivo.

PMID- 18708584
TI  - Recognition of misfolded proteins by Lon, a AAA(+) protease.
AB  - Proteins unfold constantly in cells, especially under stress conditions.
      Degradation of denatured polypeptides by Lon and related ATP-dependent AAA(+)
      proteases helps prevent toxic aggregates formation and other deleterious
      consequences, but how these destructive enzymatic machines distinguish between
      damaged and properly folded proteins is poorly understood. Here, we show that
      Escherichia coli Lon recognizes specific sequences -- rich in aromatic residues -
      that are accessible in unfolded polypeptides but hidden in most native
      structures. Denatured polypeptides lacking such sequences are poor substrates.
      Lon also unfolds and degrades stably folded proteins with accessible recognition
      tags. Thus, protein architecture and the positioning of appropriate targeting
      sequences allow Lon degradation to be dependent or independent of the folding
      status of a protein. Our results suggest that Lon can recognize multiple signals
      in unfolded polypeptides synergistically, resulting in nanomolar binding and a
      mechanism for discriminating irreversibly damaged proteins from transiently
      unfolded elements of structure.

PMID- 18708585
TI  - tsunami, the Dictyostelium homolog of the Fused kinase, is required for
      polarization and chemotaxis.
AB  - In a forward genetic screen for chemotaxis mutants in Dictyostelium discoideum,
      we identified a loss-of-function mutation, designated tsunami, encoding a homolog
      of the Fused kinase. Cells lacking tsuA function could not effectively perform
      chemotaxis and were unable to become polarized or correctly orient pseudopods in
      chemotactic gradients. While tsuA(-) cells were able to couple receptor occupancy
      to phosphatidylinositol (3,4,5) trisphosphate (PIP3) production and actin
      polymerization, the PIP3 response was prolonged and basal F-actin levels were
      increased. Interestingly, TsuA localizes to the microtubule network and puncta
      mainly found at the cell periphery. Analysis of the gene uncovered a novel C
      terminal domain that we designated the Tsunami Homology (TH) domain. Both the
      kinase domain and the TH domain are required to rescue the phenotypic defects of
      tsuA(-) cells. While kinase activity is not required for localization to
      microtubules, the TH domain is essential. Thus, localization of kinase activity
      to microtubules is critical for TsuA function. We propose that functions in
      association with the microtubule network may underlie the divergent roles of
      Fused kinase proteins in different organisms.

PMID- 18708586
TI  - Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis
      factor-alpha-induced inflammation with extraordinary potency.
AB  - The G protein-coupled serotonin 5-hydroxytryptamine (5-HT)(2A) receptor is
      primarily recognized for its role in brain neurotransmission, where it mediates a
      wide variety of functions, including certain aspects of cognition. However, there
      is significant expression of this receptor in peripheral tissues, where its
      importance is largely unknown. We have now discovered that activation of 5-HT(2A)
      receptors in primary aortic smooth muscle cells provides a previously unknown and
      extremely potent inhibition of tumor necrosis factor (TNF)-alpha-mediated
      inflammation. 5-HT(2A) receptor stimulation with the agonist (R)-1-(2,5-dimethoxy
      4-iodophenyl)-2-aminopropane [(R)-DOI] rapidly inhibits a variety of TNF-alpha
      mediated proinflammatory markers, including intracellular adhesion molecule 1
      (ICAM-1), vascular adhesion molecule 1 (VCAM-1), and interleukin (IL)-6 gene
      expression, nitric-oxide synthase activity, and nuclear translocation of nuclear
      factor kappaB, with IC(50) values of only 10 to 20 pM. It is significant that
      proinflammatory markers can also be inhibited by (R)-DOI hours after treatment
      with TNF-alpha. With the exception of a few natural toxins, no current drugs or
      small molecule therapeutics demonstrate a comparable potency for any
      physiological effect. TNF-alpha-mediated inflammatory pathways have been strongly
      implicated in a number of diseases, including atherosclerosis, rheumatoid
      arthritis, psoriasis, type II diabetes, depression, schizophrenia, and
      Alzheimer's disease. Our results indicate that activation of 5-HT(2A) receptors
      represents a novel, and extraordinarily potent, potential therapeutic avenue for
      the treatment of disorders involving TNF-alpha-mediated inflammation. Note that
      because (R)-DOI can significantly inhibit the effects of TNF-alpha many hours
      after the administration of TNF-alpha, potential therapies could be aimed not
      only at preventing inflammation but also treating inflammatory injury that has
      already occurred or is ongoing.

PMID- 18708587
TI  - The volatile anesthetic isoflurane perturbs conformational activation of integrin
      LFA-1 by binding to the allosteric regulatory cavity.
AB  - The molecular and structural basis of anesthetic interactions with conformations
      and functionalities of cell surface receptors remains to be elucidated. We have
      demonstrated that the widely used volatile anesthetic isoflurane blocks the
      activation-dependent conformational conversion of integrin lymphocyte function
      associated antigen-1 (LFA-1), the major leukocyte cell adhesion molecule, to a
      high-affinity configuration. Perturbation of LFA-1 activation by isoflurane at
      clinically relevant concentrations leads to the inhibition of T-cell interactions
      with target cells as well as ligand-triggered intracellular signaling. Nuclear
      magnetic resonance spectroscopy reveals that isoflurane binds within a cavity in
      the LFA-1 ligand-binding domain, which is a previously identified drug-binding
      site for allosteric small-molecule antagonists that stabilize LFA-1 in a low
      affinity conformation. These results provide a potential mechanism for the
      immunomodulatory properties of isoflurane.

PMID- 18708588
TI  - NFAT regulates induction of COX-2 and apoptosis of keratinocytes in response to
      ultraviolet radiation exposure.
AB  - The nuclear factor of activated T cells (NFAT) transcription factors are
      regulated by calcium/calcineurin signals and play important roles in T cells,
      muscle, bone, and neural tissue. NFAT is expressed in the epidermis, and although
      recent data suggest that NFAT is involved in the skin's responses to ultraviolet
      radiation (UVR), the wavelengths of radiation that activate NFAT and the
      biological function of UV-activated NFAT remain undefined. We demonstrate that
      NFAT transcriptional activity is preferentially induced by UVB wavelengths in
      keratinocytes. The derived action spectrum for NFAT activation indicates that
      NFAT transcriptional activity is inversely associated with wavelength. UVR also
      evoked NFAT2 nuclear translocation in a parallel wavelength-dependent fashion and
      both transcriptional activation and nuclear translocation were inhibited by the
      calcineurin inhibitor cyclosporin A. UVR also evoked NFAT2 nuclear translocation
      in three-dimensional skin equivalents. Evidence suggests that COX-2 contributes
      to UV-induced carcinogenesis. Inhibiting UV-induced NFAT activation in
      keratinocytes, reduced COX-2 protein induction, and increased UV-induced
      apoptosis. COX-2 luciferase reporters lacking functional NFAT binding sites were
      less responsive to UVR, highlighting that NFAT is required for UV-induced COX-2
      induction. Taken together, these data suggest that the proinflammatory,
      antiapoptotic, and procarcinogenic functions of UV-activated COX-2 may be
      mediated, in part, by upstream NFAT signaling.

PMID- 18708589
TI  - Mutations in cystathionine beta-synthase or methylenetetrahydrofolate reductase
      gene increase N-homocysteinylated protein levels in humans.
AB  - Severely elevated plasma homocysteine (Hcy) levels observed in genetic disorders
      of Hcy metabolism are associated with pathologies in multiple organs and lead to
      premature death due to vascular complications. In addition to elevating plasma
      Hcy, mutations in cystathionine beta-synthase (CBS) or methylenetetrahydrofolate
      reductase (MTHFR) gene lead to markedly elevated levels of circulating Hcy
      thiolactone. The thiooester chemistry of Hcy-thiolactone underlies its ability to
      form isopeptide bonds with protein lysine residues (N-Hcy-protein), which may
      impair or alter the protein's function. However, it was not known whether genetic
      deficiencies in Hcy metabolism affect N-Hcy-protein levels in humans. Here we
      show that plasma N-Hcy-protein levels are significantly elevated in CBS- and
      MTHFR-deficient patients. We also show that CBS-deficient patients have
      significantly elevated plasma levels of prothrombotic N-Hcy-fibrinogen. These
      results provide a possible explanation for increased atherothrombosis observed in
      CBS-deficient patients.

PMID- 18708590
TI  - Helminth 2-Cys peroxiredoxin drives Th2 responses through a mechanism involving
      alternatively activated macrophages.
AB  - During helminth infections, alternatively activated macrophages (AAMacs) are key
      to promoting Th2 responses and suppressing Th1-driven inflammatory pathology. Th2
      cytokines IL-4 and/or IL-13 are believed to be important in the induction and
      activation of AAMacs. Using murine models for the helminth infections caused by
      Fasciola hepatica (Fh) and Schistosoma mansoni (Sm), we show that a secreted
      antioxidant, peroxiredoxin (Prx), induces alternative activation of macrophages.
      These activated, Ym1-expressing macrophages enhanced the secretion of IL-4, IL-5,
      and IL-13 from naive CD4(+) T cells. Administration of recombinant FhPrx and
      SmPrx to wild-type and IL-4(-/-) and IL-13(-/-) mice induced the production of
      AAMacs. In addition, Prx stimulated the expression of markers of AAMacs
      (particularly, Ym1) in vitro, and therefore can act independently of IL-4/IL-13
      signaling. The immunomodulatory property of Prx is not due to its antioxidant
      activity, as an inactive recombinant variant with active site Cys residues
      replaced by Gly could also induce AAMacs and Th2 responses. Immunization of mice
      with recombinant Prx or passive transfer of anti-Prx antibodies prior to
      infection with Fh not only blocked the induction of AAMacs but also the
      development of parasite-specific Th2 responses. We propose that Prx activates
      macrophages as an initial step in the induction of Th2 responses by helminth
      parasites and is thereby a novel pathogen-associated molecular pattern.

PMID- 18708591
TI  - Apelin/APJ signaling system: a potential link between adipose tissue and
      endothelial angiogenic processes.
AB  - Adipose tissue is an active endocrine organ that produces a variety of secretory
      factors involved in the initiation of angiogenic processes. The bioactive peptide
      apelin is the endogenous ligand of the G protein-coupled receptor, APJ. Here we
      investigated the potential role of apelin and its receptor, APJ, in the
      angiogenic responses of human endothelial cells and the development of a
      functional vascular network in a model of adipose tissue development in mice.
      Treatment of human umbilical vein endothelial cells with apelin dose-dependently
      increased angiogenic responses, including endothelial cell migration,
      proliferation, and Matrigel(R) capillary tubelike structure formation. These
      endothelial effects of apelin were due to activation of APJ, because siRNA
      directed against APJ, which led to long-lasting down-regulation of APJ mRNA,
      abolished cell migration induced by apelin in contrast to control nonsilencing
      siRNA. Hypoxia up-regulated the expression of apelin in 3T3F442A adipocytes, and
      we therefore determined whether apelin could play a role in adipose tissue
      angiogenesis in vivo. Epididymal white adipose tissue (EWAT) transplantation was
      performed as a model of adipose tissue angiogenesis. Transplantation led to
      increased apelin mRNA levels 2 and 5 days after transplantation associated with
      tissue hypoxia, as evidenced by hydroxyprobe staining on tissue sections. Graft
      revascularization evolved in parallel, as the first functional vessels in EWAT
      grafts were observed 2 days after transplantation and a strong angiogenic
      response was apparent on day 14. This was confirmed by determination of graft
      hemoglobin levels, which are indicative of functional vascularization and were
      strongly increased 5 and 14 days after transplantation. The role of apelin in the
      graft neovascularization was then assessed by local delivery of stable complex
      apelin-targeting siRNA leading to dramatically reduced apelin mRNA levels and
      vascularization (quantified by hemogloblin content) in grafted EWAT on day 5 when
      compared with control siRNA. Taken together, our data provide the first evidence
      that apelin/APJ signaling pathways play a critical role in the development of the
      functional vascular network in adipose tissue. In addition, we have shown that
      adipocyte-derived apelin can be up-regulated by hypoxia. These findings provide
      novel insights into the complex relationship between adipose tissue and
      endothelial vascular function and may lead to new therapeutic strategies to
      modulate angiogenesis.

PMID- 18708592
TI  - CD5-low expression lymphocytes in canine peripheral blood show characteristics of
      natural killer cells.
AB  - NK cell markers and receptors have been discovered in many mammalian species,
      such as humans, mice, rats, pigs, and cows. However, there is still a lack of
      information concerning NK cell markers or receptors in canines. We have
      discovered that canine CD5-low density (CD5lo) cells in PBL are closely
      associated with NK cell characteristics. CD5lo cells comprised 14.9 +/- 6.68% of
      the total PBL. A high proportion of the CD5lo cell population expressed CD3
      (96.6%), CD8alpha (77.7%), CD8beta (53%), alpha/beta TCR (83%), and CD11/18
      (80%), but the expression of gamma/delta TCR (6.5%), CD4 (10.6%), and CD21 (2.4%)
      was low. CD5lo cells were larger than CD5-high density (CD5hi) cells. Light and
      electron microscopy revealed numerous large cytoplasmic granules in CD5lo cells,
      especially after IL-2 stimulation, which was in contrast to CD5hi, in which
      intracytoplasmic granules were not frequently seen. After IL-2 stimulation, CD5lo
      cells had significantly stronger NK cytotoxicity than CD5hi cells. CD5lo cells
      had much higher mRNA levels for NKG2D, CD16, CD94, CD160, perforin, and granzyme
      than CD5hi. Following IL-2 stimulation, CD5lo cells had significantly higher mRNA
      levels of NKp30, NKp44, CD16, and CD94 than CD5hi cells. In addition, IL-2
      stimulated, CD5lo-depleted PBL showed a loss of NK cytotoxicity. CD5lo cells also
      showed significantly lower antigen-specific cytotoxic T cell activity as compared
      with CD5hi cells. Taken together, the CD5lo subset in canine PBL is closely
      related to canine NK cells, and CD5lo can be used as a phenotypic marker for an
      IL-2-dependent canine NK cell enrichment.

PMID- 18708594
TI  - Effect of diet containing phytate and phytase on the activity and messenger
      ribonucleic acid expression of carbohydrase and transporter in chickens.
AB  - The effect of dietary phytate and phytase on carbohydrase activity and hexose
      transport was investigated in broiler chickens. Diets containing phytate P (2.2
      or 4.4 g/kg) with different phytase dose rates (0, 500, or 1,000 phytase
      units/kg) were fed to 504 female Cobb chicks for 3 wk. Diets containing high
      phytate concentrations depressed (P < 0.05) BW and G:F, whereas phytase
      supplementation improved (P < 0.05) the performance of birds. In the duodenum,
      phytate decreased (P < 0.05) the activities of disaccharidases, Na(+)K(+)-ATPase,
      and glucose concentrations by 5 to 11%, but phytase enhanced (P < 0.05) the
      concentrations of amylase, sucrase, maltase, Na(+)K(+)-ATPase, and glucose by 5
      to 30%. In the jejunum, phytate decreased (P < 0.05) the concentrations of
      amylase, sucrase, Na(+)K(+)-ATPase, and glucose by 10 to 22%, and phytase
      alleviated the negative effect of phytate on the above variables. Ingestion of
      diets containing phytate also decreased (P < 0.05) serum amylase activity and
      glucose concentration, and phytase enhanced (P < 0.05) serum concentrations of
      amylase, sucrase, maltase, Na(+)K(+)-ATPase, and glucose. There were also
      interactions (P < 0.05) between phytate and phytase on the concentrations of
      serum amylase, duodenal amylase, sucrase, and jejunal glucose. Enzymatic analysis
      at a molecular level showed that neither phytate nor phytase influenced the mRNA
      expression of sucrase-isomaltase in the small intestine. Also, the investigation
      into the sodium glucose cotransporter gene may challenge the mechanism by which
      phytate interferes with glucose utilization, as partly indicated by bird
      performance, and transmembrane transport because diets containing increased
      phytate upregulated (P < 0.05) the mRNA expression of the sodium glucose
      cotransporter gene in duodenum and did not influence it in the jejunum. These
      results indicate that phytate can impair endogenous carbohydrase activity and
      digestive competence, and phytase can ameliorate these effects for chickens.

PMID- 18708593
TI  - TLR4-mediated activation of dendritic cells by the heat shock protein DnaK from
      Francisella tularensis.
AB  - Francisella tularensis is the causative agent of tularemia, a severe,
      debilitating disease of humans and other mammals. As this microorganism is also
      classified as a "category-A pathogen" and a potential biowarfare agent, there is
      a need for an effective vaccine. Several antigens of F. tularensis, including the
      heat shock protein DnaK, have been proposed for use in a potential subunit
      vaccine. In this study, we characterized the innate immune response of murine
      bone marrow-derived dendritic cells (DC) to F. tularensis DnaK. Recombinant DnaK
      was produced using a bacterial expression system and purified using affinity, ion
      exchange, and size-exclusion chromatography. DnaK induced the activation of MAPKs
      and NF-kappaB in DC and the production of the proinflammatory cytokines IL-6, TNF
      alpha, and IL-12 p40, as well as low levels of IL-10. DnaK induced phenotypic
      maturation of DC, as demonstrated by an up-regulation of costimulatory molecules
      CD40, CD80, and CD86. DnaK stimulated DC through TLR4 and the adapters MyD88 and
      Toll/IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) that mediated
      differential responses. DnaK induced activation of MAPKs and NF-kappaB in a MyD88
      or TRIF-dependent manner. However, the presence of MyD88- and TRIF-dependent
      signaling pathways was essential for an optimal, DnaK-induced cytokine response
      in DC. In contrast, DnaK induced DC maturation in a TRIF-dependent, MyD88
      independent manner. These results provide insight about the molecular
      interactions between an immunodominant antigen of F. tularensis and host immune
      cells, which is crucial for the rational design and development of a safe and
      efficacious vaccine against tularemia.

PMID- 18708595
TI  - Pathogen-dependent induction of cytokines and other soluble inflammatory
      mediators during intramammary infection of dairy cows.
AB  - Mastitis is a highly prevalent and costly disease of dairy cows that is commonly
      caused by intramammary bacterial infection. The innate immune response to
      bacterial penetration of the mammary gland is evoked within hours of infection,
      and the rapidity and magnitude of this response have been demonstrated to
      influence the resolution of this disease. Cytokines and other mediators of
      inflammation are known to play critical roles in the innate immune response to
      intramammary infection. The objectives of this review are to summarize the
      current understanding of the cytokine response to intramammary infection,
      highlight recent findings identifying differences in the cytokine response to
      various bacterial pathogens, and discuss future research directions that will
      increase our knowledge of the role of inflammatory mediators in predicting and
      governing the outcome of mastitis.

PMID- 18708596
TI  - Citrulline and intestinal fatty acid-binding protein: longitudinal markers of
      postweaning small intestinal function in pigs?
AB  - The objective of the current study was to investigate whether plasma citrulline
      or intestinal fatty acid-binding protein (I-FABP) concentrations might be used as
      longitudinal markers for small intestinal function in piglets after weaning.
      Plasma citrulline and I-FABP concentrations were measured longitudinally in
      weaned and unweaned piglets, and related to intestinal absorption values (i.e.,
      plasma mannitol and 3-xylose concentrations in a sugar absorption test). Within
      each litter (n = 10), 2 piglets with a close-to-litter-average BW were selected.
      At 20.8 +/- 0.4 d of age, the selected piglets per litter were either weaned
      conventionally (CW) or remained with the sow (UNW). One day before, and 0.5, 2,
      4, and 7 d after weaning of the CW piglets, the selected piglets of both groups
      were subjected to a sugar absorption test. After a 2-h fast, piglets were
      administered an oral dose of 2 mL/kg of sugar solution, containing 50 mg/kg of
      mannitol and 100 mg/kg of 3-xylose. One hour after administration, a blood sample
      was collected from a jugular vein for determination of plasma I-FABP, citrulline,
      mannitol, and 3-xylose concentrations. Plasma I-FABP concentration showed great
      variation within treatments, and no difference was observed in plasma I-FABP
      concentrations between the CW and UNW treatments (P = 0.63). The absorption of 3
      xylose was not different between treatments (P = 0.83). Mannitol absorption,
      however, was less in the weaned CW piglets compared with the UNW piglets (P =
      0.003), with the nadir on d 4 postweaning. Weaning also reduced plasma citrulline
      concentrations in the CW treatment compared with the UNW treatment (P < 0.001).
      On d 4 and 7 postweaning, plasma citrulline concentrations of CW piglets were
      less (P < 0.001 and P = 0.0013) than preweaning values. Furthermore, in the CW
      treatment, plasma citrulline concentrations correlated with plasma mannitol
      concentrations at d 4 postweaning (r = 0.89, P = 0.008) and overall (r = 0.76, P
      = 0.001). Based on these results, plasma citrulline concentration seems to be a
      possible marker for monitoring intestinal function in pigs after weaning.

PMID- 18708597
TI  - ASAS Centennial Paper: Developments and future outlook for preharvest food
      safety.
AB  - The last century of food animal agriculture is a remarkable triumph of scientific
      research. Knowledge derived through research has resulted in the development and
      use of new technologies that have increased the efficiency of food production and
      created a huge animal production and food manufacturing industry capable of
      feeding the US population while also providing significant quantities of high
      quality food for export to other countries. Although the US food supply is among
      the safest in the world, the US Center for Disease Prevention and Control
      estimates that 76 million people get sick, more than 300,000 are hospitalized,
      and 5,000 die each year from foodborne illness. Consequently, preventing
      foodborne illness and death remains a major public health concern. Challenges to
      providing a safe, abundant, and nutritious food supply are complex because all
      aspects of food production, from farm to fork, must be considered. Given the
      national and international demand and expectations for food safety as well as the
      formidable challenges of producing and maintaining a safe food supply, food
      safety research and educational programs have taken on a new urgency. Remarkable
      progress has been made during the last century. Wisdom from a century of animal
      agriculture research now includes the realization that on-farm pathogens are
      intricately associated with animal health and well-being, the production of high
      quality food, and profitability. In this review, some of the developments that
      have occurred over the last few decades are summarized, including types, sources,
      and concentrations of disease-causing pathogens encountered in food-producing
      animal environments and their association with food safety; current and future
      methods to control or reduce foodborne pathogens on the farm; and present and
      future preharvest food safety research directions. Future scientific
      breakthroughs will no doubt have a profound impact on animal agriculture and the
      production of high-quality food, but we will also be faced with moral, ethical,
      and societal dilemmas that must be reconciled. A strong, science-based approach
      that addresses all the complex issues involved in continuing to improve food
      safety and public health is necessary to prevent foodborne illnesses. Not only
      must research be conducted to solve complex food safety issues, but results of
      that research must also be communicated effectively to producers and consumers.

PMID- 18708598
TI  - Energy requirements of Texel crossbred lambs.
AB  - Two trials were conducted to determine the energy requirements of feedlot Texel
      crossbred lambs. In a comparative slaughter trial, thirty 11/16 Texel x 5/16 Ile
      de France crossbred noncastrated male lambs, weaned at 42 d of age (16.2 +/- 2.1
      kg of shrunk BW; SBW), were used. Five lambs were randomly chosen and slaughtered
      after 10 d of experimental management and diet adaptation (baseline group).
      Fifteen lambs then were fed for ad libitum intake and slaughtered at 25, 30, or
      35 kg of SBW. The remaining 10 lambs were randomly assigned to 2 levels of DMI,
      either 70 or 55% of the ad libitum intake, and were slaughtered concomitantly
      with lambs of the 35 kg of SBW group. Total body N, fat, and energy contents were
      determined. In a digestibility trial, 6 Texel x Ile de France crossbred lambs
      (30.4 +/- 2.6 kg of SBW) were housed in metabolic cages and used in a replicated
      3 x 3 Latin square experiment to evaluate the energetic value of the diet at
      different feed intake levels. Net and ME requirements for maintenance were 58.6
      and 91 kcal/kg(0.75) of SBW, respectively. Consequently, partial efficiency of
      energy use for maintenance was 0.64. Body fat content varied from 72.7 to 125.9
      g/kg of empty BW, respectively, for 13.1 and 28.2 kg of empty BW. Net energy
      requirements for growth of lambs at 15 and 35 kg of SBW at an ADG of 250 g were
      424 and 553 kcal/d, respectively. Partial efficiency of energy use for growth was
      0.47. Texel x Ile de France crossbred growing lambs used in this study showed
      decreased nutritional requirements than those reported by most nutritional
      systems.

PMID- 18708599
TI  - Effects of shaded versus unshaded wallows on behavior, performance, and
      physiology of the outdoor lactating sow.
AB  - The objectives of this study were to determine the effects of shading wallows
      during the summer months on lactating sow behavior, performance, and physiology.
      A total of 128 sows were used during warm weather (May to August 2001) to
      determine the effects of unshaded (control; n = 8) vs. shaded (SH; n = 8)
      wallows. Sows ranged over 6 parities and were fed a completely balanced sorghum
      based diet. Behavioral data were collected by 15-min scan samples over a 24-h
      period/wk for a total of 16 wk. All sows were observed twice when litter age was
      5 and 15 d, respectively. Respiration rates (breaths/min) were collected on 50
      sows (control, n = 25; SH, n = 25) over an 8-wk period when the maximum
      temperature exceeded 32 degrees C. Ten milliliters of clotted blood and 20 mL of
      whole blood were obtained by jugular puncture from each sow on the day of weaning
      to determine total white blood cells, acute phase proteins, packed-cell volume,
      and chemotaxis and chemokinesis. Descriptive water temperature profiles were
      measured by using data loggers positioned at 3 levels per wallow: surface water,
      shallow mud, and deep mud. Behavioral, postural, location, performance, and
      physiological measurements did not differ (P > 0.05) among wallow treatments.
      Regardless of treatment, sows spent approximately 82% of their total time budget
      inside the farrowing hut and only approximately 7% of their total time budget in
      the wallow. A total of 428 piglets died, 219 in the control treatment and 209 in
      the SH treatment. The majority of piglets in both treatments died of crushing
      within the first 72 h after parturition, and most of the piglets had suckled.
      Shade kept the shallow water profile cooler during the hotter afternoon
      temperatures compared with the control wallows. In SH for both the shallow and
      deep mud profiles, temperatures were consistent throughout the day. In
      conclusion, sows spent a large percentage of their daily time budget inside the
      farrowing hut and spent only brief episodes in the wallow. Shading the wallow did
      not result in increased wallow use time or improvements in sow physiology and
      overall performance.

PMID- 18708600
TI  - Differential response of cull cow muscles to the hypertrophic actions of
      ractopamine-hydrogen chloride.
AB  - Ractopamine-HCl (RAC) is a beta-adrenergic agonist with variable effects on
      cattle performance and carcass variables. Cull cows fed RAC (200 mg . head(-1) .
      d(-1)) demonstrate an increased size of type I and II muscle fibers that does not
      translate into a larger ribeye area. The objective of this study was to examine
      the dose-dependent effects of RAC on cull cow muscle morphometrics. Eighty-eight
      cull beef cows representing 2 breed types (n = 44 each) were fed 0, 100, 200, and
      300 mg . head(-1) . d(-1) of RAC for the last 28 d of a 54-d feeding period. On d
      54, cows were slaughtered, and samples of the LM and semimembranosus muscle (SM)
      from 16 randomly selected carcasses (n = 4 per treatment) were taken for
      measurement of beta (2)-adrenergic receptors and type I, IIA, and IIX myosin
      heavy chain (MyHC) gene expression. Twenty-four hours postmortem, LM, SM,
      infraspinatus (INF), and vastus lateralis samples from 40 randomly selected
      carcasses (n = 10 per treatment) were obtained and frozen for immunohistochemical
      analysis. Muscle fiber cross-sectional area and diameter, MyHC isoform
      expression, and fiber-associated nuclei numbers were measured. Ractopamine dosage
      exhibited differential effects on muscle morphometrics and MyHC gene expression.
      Muscle fiber cross-sectional area and diameter were increased (P < 0.05) by RAC
      in INF type I and IIA fibers and SM type IIA fibers. Ractopamine increased (P <
      0.05) MyHC type IIX mRNA and tended to increase (P < 0.10) beta(2)-adrenergic
      receptors in the SM; a change in mRNA abundance was not detected for either gene
      in the LM. Treatment with RAC decreased (P < 0.05) fiber-associated nuclei
      numbers in the INF, vastus lateralis, and LM but did not affect (P > 0.05) MyHC
      or beta-adrenergic receptor expression. These results indicate that cull cow
      feeding programs may consider supplementing RAC as a means of adding value to
      cuts within the chuck, such as the INF.

PMID- 18708601
TI  - Relationships between monounsaturated fatty acids of marbling flecks and image
      analysis traits in longissimus muscle for Japanese Black steers.
AB  - The percentage of MUFA to total fatty acids of beef differs among intermuscular,
      intramuscular, and subcutaneous fat even within an individual cow. Our objective
      was to investigate the variation of the percentage of MUFA by geometric and
      sectional change of marbling flecks in rib eye. Longissimus muscles of 8 Japanese
      Black steers from a common sire and a common maternal grand sire were used. Three
      slices (1 from rib roast and 2 from sirloin) from each animal were selected for
      analysis. Five marbling flecks from each slice were randomly taken to obtain the
      percentage of MUFA using gas chromatography. High-quality digital images of all
      slices were taken with a mirror-type camera. The area and location of each
      marbling fleck were calculated by image analysis. The marbling flecks were
      categorized by area [small <0.4 cm(2), medium 0.4 to 2.0 cm(2), large >2.0
      cm(2)], by location (dorsal and ventral), and by slice section through the LM
      (front, middle, and back). The effects of classification according to the area,
      location, and slice section were statistically significant (P < 0.05) for the
      percentage of MUFA. Least squares means of the percentage of MUFA for marbling
      flecks of sizes small, medium, and large were 56.8, 58.4, and 60.2%,
      respectively, indicating that larger marbling flecks had greater MUFA (P < 0.05).
      Those of dorsal, ventral, front, middle, and back were 59.1, 57.8, 55.4, 59.9,
      and 60.1%, respectively. The percentages of MUFA of the marbling flecks located
      in the dorsal part were greater than those in the ventral part (P < 0.05). The
      percentages of MUFA from middle and back were greater than those from front (P <
      0.01). We suggest that the area, location, and slice section of marbling would be
      the determining factors for the percentage of MUFA of marbling.

PMID- 18708602
TI  - Nonionophore antibiotics do not affect the trans-18:1 and conjugated linoleic
      acid composition in beef adipose tissue.
AB  - The common practice in North American feedlot industries is to add antibiotics to
      the diet to prevent disease and improve both BW gain and feed efficiency. In this
      study, 240 crossbred steer calves were backgrounded on a 54% silage diet for 80 d
      and fed a finishing diet consisting of 81% barley grain, 10% barley silage, and
      7.5% supplement (DM basis) with and without in-feed antibiotics for approximately
      120 d. Calves were assigned to 1 of 5 treatments: a control with no antibiotics,
      11 mg/kg of chlortetracycline, 44 mg/kg of chlortetracycline, 44 mg/kg of
      chlortetracycline plus 44 mg/kg of sulfamethazine, and 11 mg/ kg of tylosin
      phosphate. A combination of GLC and silver-ion HPLC methods was used to analyze
      the fatty acid composition of brisket adipose tissue, with emphasis on trans-18:1
      and CLA isomers. The inclusion of nonionophore antibiotics in the diet had little
      effect on the fatty acid composition, except that feeding either 44 mg/kg of
      chlortetracycline or 11 mg/kg of tylosin caused small increases in 9c-14:1 and
      16:0 relative to the control (0.26 and 0.9 g/100 g of total fatty acids,
      respectively). Likewise, profiles of trans-18:1 and CLA isomers were unchanged by
      antibiotics, but across treatments the predominant trans-18:1 isomer was 10t-18:1
      (where t = trans; 3.22%) at 3 times the concentration of the second most abundant
      isomer (11t-18:1; vaccenic acid, 1.05%). Rumenic acid (9c,11t-18:2, where c =
      cis) was the major CLA isomer at 61% of total CLA, followed by 7t,9c-18:2 at 9%.
      Because no other effects on fatty acid composition were evident, data for trans
      18:1 and CLA were pooled across treatments to investigate possible relationships
      among rumen PUFA metabolites. The total trans-18:1 content in brisket adipose
      tissue was positively correlated with 10t-18:1, but not with 11t-18:1, whereas
      the total CLA was positively correlated with 9c,11t-18:2, but not with 7t,9c
      18:2. The 7t,9c-18:2 was, however, positively correlated with 10t-18:1 and
      6t/7t/8t-18:1 but was negatively correlated with rumenic acid. These metabolic
      interrelationships suggest the presence of bacterial populations with distinct
      pathways for PUFA biohydrogenation in which either 10t-18:1 or 11t-18:1
      predominate. Overall, the nonionophore antibiotics tested did not appreciably
      change adipose tissue composition and consequently could not be used to improve
      the trans-18:1 or CLA profile (i.e., increase vaccenic and rumenic acids at the
      expense of 10t-18:1).

PMID- 18708603
TI  - Milk yield, milk composition, eating behavior, and lamb performance of ewes fed
      diets containing soybean hulls replacing coastcross (Cynodon species) hay.
AB  - The objective of this experiment was to evaluate the effects of replacing
      coastcross hay NDF by soybean hull (SH) NDF on the lactation performance and
      eating behavior of ewes and also on the performance of their lambs. Fifty-six
      Santa Ines lactating ewes (56.1 +/- 6.8 kg of initial BW; mean +/- SD) were
      penned individually and used in a randomized complete block design with 14 blocks
      and 4 treatments. Diets were formulated to provide similar concentrations of NDF
      (56%) and CP (16%). The SH NDF replaced 33 (SH33), 67 (SH67), or 100% (SH100) of
      the NDF contributed by coastcross hay in a 70% forage-based diet (SH0), resulting
      in SH inclusion rates of 0, 25, 54, and 85% of the dietary DM. Once a week, from
      the second to the eighth week of lactation (weaning time), ewes were separated
      from their lambs, stimulated by a 6-IU i.v. oxytocin injection, and hand milked
      to empty the udder. After 3 h, milk production was obtained after the same
      procedure. Quadratic effect for milk production (142.4, 179.8, 212.6, and 202.9
      g/3 h) and cubic effect for DMI (2.27, 2.69, 3.25, and 3.00 kg/d) were observed
      as SH inclusion increased from 0 to 85% of the dietary DM. Milk fat (7.59, 7.86,
      7.59, and 7.74%), protein (4.53, 4.43, 4.40, and 4.55%), and total solids (18.24,
      18.54, 18.39, and 18.64%) did not differ among the 70% forage-based diet and
      diets with SH NDF replacing 33, 67, or 100% of the NDF. A linear increase in
      lactose concentration was observed with SH inclusion. Ewe BW gain during the
      trial showed a cubic response (0.37, 0.03, 4.80, and 2.80 kg) with SH inclusion.
      The preweaning ADG of lambs increased linearly, and ADG of lambs after weaning
      decreased linearly with SH inclusion. Final BW of lambs (2 wk after weaning) did
      not differ among treatments. Eating behavior observations were conducted with 44
      ewes. The same facilities, experimental design, dietary treatments, and feeding
      management were used. Observations were visually recorded every 5 min for a 24-h
      period when ewes were 46 +/- 6.8 d in milk. Eating time (min/d, min/g of DMI, and
      min/g of NDF intake) and time expended in rumination and chewing activities
      (min/g of DMI and min/g of NDF intake) decreased linearly with the addition of SH
      in the diets. The inclusion of SH improved DMI and milk production, also
      reflecting on the BW of lambs at weaning. Milk performance was not affected when
      SH NDF replaced 100% of hay NDF.

PMID- 18708604
TI  - ASAS Centennial Paper: Development of a corn-based beef industry.
AB  - The development of a beef industry, heavily dependent on corn utilization, began
      to occur in the 1940s. Begun as a means to add value to the grain while improving
      consumer acceptance of beef, corn has become an integral part of beef production.
      Developments in the 21st century including unprecedented cattle prices, changes
      in beef demand, bovine spongiform encephalopathy, surge in energy costs, pricing
      differentiation of cattle prices based on quality, and industry consolidation
      have dramatically changed the price of corn and cost of beef production. The
      future of the beef industry will be dependent on our ability to continue
      producing high-quality beef for a global market through effective use of
      genetics, new technologies, and economic management strategies.

PMID- 18708605
TI  - Effect of supplemental energy source and frequency on growing calf performance.
AB  - Crossbred heifers (n = 120; 265 kg, SD = 37) were fed individually (84 d) to
      determine the effect of supplement type, concentration, and frequency on intake
      and performance and to estimate the energy value of dry distillers grains plus
      solubles (DDGS) in a high-forage diet. Treatments were arranged in a 3 x 2 x 2
      factorial, with 3 supplements, 2 concentrations, and 2 frequencies of
      supplementation. Supplements including dry-rolled corn (DRC), DRC with corn
      gluten meal (DRC + CGM), and DDGS were fed at 0.21% (LOW) or 0.81% (HIGH) of BW
      daily and were provided daily (DAILY) or 3 times weekly (ALT). Heifers were fed
      to consume grass hay (8.7% CP) ad libitum. Individual DMI, diet composition, BW,
      and ADG were used to calculate energy values for DDGS and DRC. Supplement type,
      concentration, frequency, and interactions were tested using the MIXED procedure
      of SAS, with BW included as a covariate. Supplement x concentration interactions
      for gain (P = 0.01) and G:F (P < 0.01) were detected. At the LOW concentration,
      heifers supplemented with DDGS gained more and were more efficient (P </= 0.03)
      than those supplemented with DRC or DRC + CGM. No performance differences were
      observed (P >/= 0.22) between DDGS and DRC + CGM in HIGH treatments, although
      both improved (P </= 0.01) gain and G:F relative to DRC. Calculated TDN content
      of DDGS was 18 to 30% greater than DRC. Gain and G:F were improved (P < 0.01) in
      heifers fed HIGH vs. LOW. Total intake was greater (P < 0.01) for HIGH than LOW,
      but LOW heifers consumed more hay (P < 0.01) than HIGH. The DAILY heifers
      consumed more (P < 0.01) hay and total DM than the ALT heifers. The DAILY heifers
      gained more (P < 0.01) than ALT, but G:F was not affected (P = 0.85) by
      supplementation frequency. In a high-forage diet, DDGS has greater energy value
      than corn.

PMID- 18708606
TI  - Single nucleotide polymorphisms in several porcine cathepsin genes are associated
      with growth, carcass, and production traits in Italian Large White pigs.
AB  - To identify DNA markers associated with performance, carcass, and meat production
      traits including muscle postmortem cathepsin activity, several porcine genes
      encoding for lysosomal proteinases (cathepsin B, CTSB; cathepsin D, CTSD;
      cathepsin F, CTSF; cathepsin H, CTSH; cathepsin L, CTSL; and cathepsin Z, CTSZ)
      and for a cathepsin inhibitor (cystatin B) were investigated. Single nucleotide
      polymorphisms were identified in CTSD, CTSH, CTSL, and CTSZ genes with a
      combination of in silico expressed sequence tag database mining and single-strand
      conformation polymorphism analysis. Sequencing and PCR-RFLP protocols were used
      to validate the identified polymorphisms. Allele frequencies at these loci were
      investigated in Italian Large White, Landrace, Duroc, Pietrain, Belgian Landrace,
      Hampshire, and Meishan breeds. Genotyping CTSD and CTSH markers made it possible
      to genetically map these genes to SSC 2 and 7, respectively. Markers in CTSD,
      CTSH, CTSL, and CTSZ genes, together with mutations we previously reported in
      cystatin B, CTSB, and CTSF genes, were genotyped in an Italian Large White sib
      tested population (272 or 482 animals). For these animals, meat quality traits
      (cathepsin B activity, pH measured at 2 h postmortem, pH measured at 24 h
      postmortem, glycogen, lactate, and glycolytic potential of semimembranosus
      muscle) and EBV for ADG, lean cuts (LC), backfat thickness (BFT), ham weight
      (HW), and feed:gain ratio (FGR) were determined. Analyzed markers did not show
      any association with muscle cathepsin B activity. Thus, it could be possible that
      different genes, other than these investigated candidates, affect this trait,
      which is correlated with the excessive softness defect of dry-cured hams. The
      results of association analysis confirmed the effects we already reported in
      another study for CTSF on ADG (P = 0.008), LC (P = 0.001), and BFT (P = 0.02).
      Moreover, CTSD was associated with ADG, LC (P < 0.0001), BFT, HW, and FGR (P <
      0.001); CTSH was associated with FGR (P = 0.026); and CTSZ was associated with
      ADG (P = 0.006), LC (P = 0.01), HW (P = 0.024), and FGR (P = 0.029). The
      biochemical and physiological functions of the lysosomal proteinases, together
      with the results obtained in our investigation, suggest that the cathepsin gene
      family might play important roles affecting economic traits in pigs.

PMID- 18708607
TI  - Manipulation of rumen ecology by dietary lemongrass (Cymbopogon citratus Stapf.)
      powder supplementation.
AB  - This experiment was conducted to investigate the effect of lemongrass [Cymbopogon
      citratus (DC.) Stapf.] powder (LGP) on rumen ecology, rumen microorganisms, and
      digestibility of nutrients. Four ruminally fistulated crossbred (Brahman native)
      beef cattle were randomly assigned according to a 4 x 4 Latin square design. The
      dietary treatments were LGP supplementation at 0, 100, 200, and 300 g/d with urea
      treated rice straw (5%) fed to allow ad libitum intake. Digestibilities of DM,
      ether extract, and NDF were significantly different among treatments and were
      greatest at 100 g/d of supplementation. However, digestibility of CP was
      decreased with LGP supplementation (P < 0.05), whereas ruminal NH(3)-N and plasma
      urea N were decreased with incremental additions of LGP (P < 0.05). Ruminal VFA
      concentrations were similar among supplementation concentrations (P > 0.05).
      Total viable bacteria, amylolytic bacteria, and cellulolytic bacteria were
      significantly different among treatments and were greatest at 100 g/d of
      supplementation (4.7 x 10(9), 1.7 x 10(7), and 2.0 x 10(9) cfu/mL, respectively).
      Protozoal populations were significantly decreased by LGP supplementation. In
      addition, efficiency of rumen microbial N synthesis based on OM truly digested in
      the rumen was enriched by LGP supplementation, especially at 100 g/d (34.2 g of
      N/kg of OM truly digested in the rumen). Based on this study, it could be
      concluded that supplementation of LGP at 100 g/d improved digestibilities of
      nutrients, rumen microbial population, and microbial protein synthesis
      efficiency, thus improving rumen ecology in beef cattle.

PMID- 18708608
TI  - Sow line differences in heat stress tolerance expressed in reproductive
      performance traits.
AB  - The objectives of this study were 1) to investigate if there were differences in
      the relation between temperature and reproductive performance traits in 2
      different sow lines, a Yorkshire line producing mainly in temperate climates and
      a Large White line producing mainly in warm climates, and 2) to determine the
      upper critical temperature (UCT) for the reproductive performance of these 2
      lines. Sows are exposed to heat stress when temperature exceeds the UCT of the
      thermo-neutral zone. Data included 32,631 observations on reproductive
      performance from 11,935 sows on 20 farms in Spain, collected from 2003 to 2005.
      Sows belonged to 2 different purebred sow lines, named D (Yorkshire sow line,
      producing mainly in temperate climates) and I (Large White sow line, producing
      mainly in warm climates). Only first insemination records per parity were used
      and were combined with the maximum outside temperature at day of insemination.
      Upper critical temperatures were studied for 3 reproduction traits: farrowing
      rate (0 or 1), litter size (range from 1 to 25), and total number of piglets born
      per first insemination (combination of farrowing rate and litter size, range from
      0 to 25). Data were corrected for fixed effects, which included parity, service
      sire, and an interaction between farm and year. Corrected data were used as
      observations in the models to study the effect of outside temperature on
      reproductive performance. Two models were compared for goodness of fit: a linear
      regression model and a plateau-linear model with the plateau representing the
      thermo-neutral zone and a linear decrease above that zone. Farrowing rate of I
      line sows was not affected by temperature. For litter size and total number born
      per first insemination of I-line sows no UCT could be estimated. These traits
      were linearly affected by temperature. For all 3 reproduction traits of the D
      line the best model was the plateau-linear model; the UCT for the D-line sows was
      estimated to be 19.2 degrees C for farrowing rate, 21.7 degrees C for litter
      size, and 19.6 degrees C for total number born per first insemination. The
      decrease in reproductive performance of I-line sows with increasing outside
      temperature was less than in D-line sows. From this study it can be concluded
      that there are differences in heat stress tolerance between sow lines as measured
      by the differences in reproductive performance. These differences are an
      indication of genetic differences in heat stress tolerance in sow lines.

PMID- 18708609
TI  - Comparison of different nonlinear functions to describe Nelore cattle growth.
AB  - This work aims to compare different nonlinear functions for describing the growth
      curves of Nelore females. The growth curve parameters, their (co)variance
      components, and environmental and genetic effects were estimated jointly through
      a Bayesian hierarchical model. In the first stage of the hierarchy, 4 nonlinear
      functions were compared: Brody, Von Bertalanffy, Gompertz, and logistic. The
      analyses were carried out using 3 different data sets to check goodness of fit
      while having animals with few records. Three different assumptions about SD of
      fitting errors were considered: constancy throughout the trajectory, linear
      increasing until 3 yr of age and constancy thereafter, and variation following
      the nonlinear function applied in the first stage of the hierarchy. Comparisons
      of the overall goodness of fit were based on Akaike information criterion, the
      Bayesian information criterion, and the deviance information criterion. Goodness
      of fit at different points of the growth curve was compared applying the
      Gelfand's check function. The posterior means of adult BW ranged from 531.78 to
      586.89 kg. Greater estimates of adult BW were observed when the fitting error
      variance was considered constant along the trajectory. The models were not
      suitable to describe the SD of fitting errors at the beginning of the growth
      curve. All functions provided less accurate predictions at the beginning of
      growth, and predictions were more accurate after 48 mo of age. The prediction of
      adult BW using nonlinear functions can be accurate when growth curve parameters
      and their (co)variance components are estimated jointly. The hierarchical model
      used in the present study can be applied to the prediction of mature BW in herds
      in which a portion of the animals are culled before adult age. Gompertz, Von
      Bertalanffy, and Brody functions were adequate to establish mean growth patterns
      and to predict the adult BW of Nelore females. The Brody model was more accurate
      in predicting the birth weight of these animals and presented the best overall
      goodness of fit.

PMID- 18708610
TI  - Genetic variation and phylogenetics of Lanyu and exotic pig breeds in Taiwan
      analyzed by nineteen microsatellite markers.
AB  - The Lanyu pig is an indigenous miniature pig breed on Lanyu Islet near Taiwan,
      with a mitochondrial DNA genetic lineage remote from Asian and European pig
      breeds. The unknown population genetic structure and increased inbreeding among
      the small population of conserved Lanyu pigs is now of great conservation
      concern. Additionally, the presence for more than a century of exotic pig breeds
      in Taiwan has made gene introgression from exotic pig breeds into Lanyu pigs very
      possible. The present study thus aimed to investigate nuclear genetic variation
      within the conserved Lanyu pigs and the phylogenetic relationship and possible
      genetic introgression between Lanyu and exotic pig breeds by determining the
      polymorphism of 19 microsatellite loci. In the neighbor-joining tree constructed
      from 7 pig breeds based on Cavalli-Sforza and Edward chord genetic distances, 3
      major clades were recognized, in which the Asian and European breeds were
      separately clustered into 2 clades with a 93.0 and 99.9% bootstrap confidence
      value, respectively. All individuals of the Lanyu breed formed a unique subclade
      within the Asian clade based on the distance of the proportion of shared alleles,
      -ln(ps), suggesting that the Lanyu breed possesses a unique nuclear genetic
      structure and that no nuclear gene introgression from exotic breeds into the
      conserved Lanyu pigs has occurred in recent history. Fifteen of 19 microsatellite
      loci deviated from Hardy-Weinberg equilibrium (by Wright's statistic), suggesting
      a significant loss of heterozygosity in the conserved population. The valuable
      nuclear genetic structure and phylogenetic information should assist future
      conservation and population management of Lanyu pigs.

PMID- 18708611
TI  - Through the eyes of a child: understanding retinopathy through ROP the
      Friedenwald lecture.

PMID- 18708612
TI  - Introducing Lois E. H. Smith, the 2008 recipient of the Friedenwald Award.

PMID- 18708613
TI  - Elastin-mediated choroidal endothelial cell migration: possible role in age
      related macular degeneration.
AB  - PURPOSE: Endothelial cell (EC) migration is a key event in angiogenesis, and is
      likely to play an important role in choroidal neovascularization in age-related
      macular degeneration (AMD). Altered elastin metabolism has been described in AMD,
      and the present study sought to determine the effects of elastin-derived peptides
      (EDPs) on choroidal EC migration and proliferation. METHODS: Migration of the
      chorioretinal EC line Rf/6a and a primary culture of human choroidal ECs through
      polycarbonate membrane inserts was quantified in the presence of elastin
      bioactive hexapeptides (BPs), EDPs, bovine serum albumin (BSA), or balanced salt
      solution. Proliferation assays and in vitro wound closure experiments were also
      performed in the presence of elastin fragments or balanced salt solution
      (control). Elastin overlay experiments were performed on sections of human eyes.
      RESULTS: For both Rf/6a and human primary choroidal ECs exposed to EDPs or BPs,
      the number of ECs that migrated through the polycarbonate membrane was
      significantly higher than ECs exposed to balanced salt solution alone or to BSA
      (P < 0.05) in all experiments. In contrast, the rate of EC proliferation did not
      significantly change in comparison to controls. Elastin binding sites were
      identified on choroidal ECs in human eyes. CONCLUSIONS: Elastin fragments
      increase choroidal EC migration, whereas they do not appear to increase or
      decrease EC proliferation. Local or systemic abnormalities in elastin physiology
      may participate in pathologic neovascular membrane formation in AMD.

PMID- 18708614
TI  - Development of a reconstructed cornea from collagen-chondroitin sulfate foams and
      human cell cultures.
AB  - PURPOSE: To develop an artificial cornea, the ability to coculture the different
      cell types present in the cornea is essential. Here the goal was to develop a
      full-thickness artificial cornea using an optimized collagen-chondroitin sulfate
      foam, with a thickness close to that of human cornea, by coculturing human
      corneal epithelial and stromal cells and transfected human endothelial cells.
      METHODS: Corneal extracellular matrix was simulated by a porous
      collagen/glycosaminoglycan-based scaffold seeded with stromal keratocytes and
      then, successively, epithelial and endothelial cells. Scaffolds were
      characterized for bulk porosity and pore size distribution. The performance of
      the three-dimensional construct was studied by histology, immunofluorescence, and
      immunohistochemistry. RESULTS: The scaffold had 85% porosity and an average pore
      size of 62.1 microm. Keratocytes populated the scaffold and produced a newly
      synthesized extracellular matrix as characterized by immunohistochemistry. Even
      though the keratocytes lost their CD34 phenotype marker, the absence of smooth
      muscle actin fibers showed that these cells had not differentiated into
      myofibroblasts. The epithelial cells formed a stratified epithelium and began
      basement membrane deposition. An endothelial cell monolayer beneath the foam was
      also apparent. CONCLUSIONS: These results demonstrate that collagen-chondroitin
      sulfate scaffolds are good substrates for artificial cornea construction with
      good resilience, long-term culture capability, and handling properties.

PMID- 18708615
TI  - Effect of ruboxistaurin on the visual acuity decline associated with long
      standing diabetic macular edema.
AB  - PURPOSE: To compare relationships between severity and duration of diabetic
      macular edema (DME) and visual acuity (VA) observed in the PKC-DRS2 with those
      from the Early Treatment Diabetic Retinopathy Study (ETDRS) and to assess the
      effect of the orally administered PKC beta inhibitor ruboxistaurin (RBX) on these
      parameters. METHODS: In the PKC-DRS2, patients with moderately severe to very
      severe nonproliferative diabetic retinopathy (n = 685) were randomly assigned to
      32 mg/d RBX or placebo and followed up for 36 months with ETDRS VA measurements
      and fundus photographs (FP) every 3 to 6 months. Mean VA was calculated across
      all FP visits for eyes in each level of the ETDRS DME severity scale at those
      visits. For eyes with baseline VA > or = 20/40, relationships between change in
      VA from baseline to last visit and duration of severe DME were analyzed with
      linear regression. RESULTS: Mean VA decreased by approximately 22 letters between
      the mildest and most severe levels of the DME scale in the PKC-DRS2, compared
      with 27 letters in the ETDRS. In the placebo group, the rate of decrease in VA
      over time associated with duration of severe DME was 0.67 letters per month (24
      letters over 36 months, compared with 20 letters over 28-36 months in the ETDRS).
      This rate was 30% less in the RBX group (0.47 letter per month, P = 0.022).
      CONCLUSIONS: The VA decrease in the PKC-DRS2 associated with long-standing DME
      agrees well with estimates from the ETDRS. RBX appears to ameliorate this
      decrease, an effect that could be important clinically. (ClinicalTrials.gov
      number, NCT00604383.).

PMID- 18708616
TI  - Exogenous collagen cross-linking reduces scleral permeability: modeling the
      effects of age-related cross-link accumulation.
AB  - PURPOSE: To investigate the relationship between scleral permeability and
      nonenzymatic cross-link density. METHODS: Scleral discs 18 mm in diameter were
      dissected from the medial and lateral equatorial regions of 60 cadaveric porcine
      eyes. Samples were incubated for 24 hours with control solution or methylglyoxal
      at concentrations of 0.001%, 0.01%, 0.10%, and 1.00%. Nonenzymatic cross-link
      density in treated and control groups was quantified with the use of papain
      digest and fluorescence spectrophotometry. Treated scleral discs were mounted in
      a customized Ussing-type chamber connected to vertical tubing, and specific
      hydraulic conductivity was determined according to the descent of a column of
      degassed saline at room temperature. Permeability to diffusion of fluorescein in
      a static chamber was determined for another set of treated scleral samples.
      RESULTS: Methylglyoxal treatment effectively increased nonenzymatic cross-link
      content, as indicated by the average fluorescence for each group. Specific
      hydraulic conductivity (m(2)) was reduced with increasing cross-link density.
      Similarly, the permeability coefficient for the fluorescein solute consistently
      decreased with increasing methylglyoxal concentration, indicating diffusion
      impedance from the treatment. CONCLUSIONS: Nonenzymatic cross-link density can be
      significantly increased by treatment with methylglyoxal. Porcine sclera showed a
      nonlinear reduction in solute permeability and specific hydraulic conductivity
      with increasing cross-link density. This model indicates that age-related
      nonenzymatic cross-link accumulation can have a substantial impact on scleral
      permeability.

PMID- 18708618
TI  - Sensory supplementation through tongue electrotactile stimulation to preserve
      head stabilization in space in the absence of vision.
AB  - PURPOSE: To investigate the effectiveness of a head position-based, tongue-placed
      biofeedback system in providing sensory supplementation to preserve head
      stability in space in the absence of visual information. METHODS: Nine healthy
      young men with normal vision and no history of previous motor problems, neck
      injury, vertigo, neurologic disease, or vestibular impairment voluntarily
      participated in the experiment. They were asked to stand, their feet placed in a
      semitandem position, as immobile as possible in two conditions of No Vision and
      Vision and two conditions of No Biofeedback and Biofeedback. In the Biofeedback
      condition, subjects executed the postural task using a biofeedback system whose
      principle consisted of supplying them with additional information about their
      head orientation/motion with respect to gravitational vertical through
      electrotactile stimulation of the tongue. A system for the analysis of movement
      was used to record the head displacements. RESULTS: Without the provision of the
      biofeedback (No Biofeedback condition), the No Vision condition yielded increased
      head displacements along the mediolateral axis compared with the Vision
      condition. Conversely, when biofeedback was available (Biofeedback condition), no
      significant difference between the No Vision and Vision conditions was observed.
      CONCLUSIONS: These results suggest that healthy young subjects were able to
      efficiently use head position-based, tongue-placed biofeedback to suppress the
      head instability induced by the suppression of vision. Hence the present findings
      demonstrate the effectiveness of a head position-based, tongue-placed biofeedback
      in providing sensory supplementation to preserve head stability in space in
      conditions of absent visual information.

PMID- 18708617
TI  - Drug delivery to posterior intraocular tissues: third Annual ARVO/Pfizer
      Ophthalmics Research Institute Conference.

PMID- 18708619
TI  - Deletion of the FHL2 gene attenuating neovascularization after corneal injury.
AB  - PURPOSE: The four-and-one-half LIM domain-containing protein2 (FHL2) is a member
      of the four-and-a-half LIM domain-only (FHL) gene family. Although FHL2 is
      expressed in the cornea, its role in angiogenesis is unclear. The aim of this
      study was to investigate the role of the FHL2 gene in corneal angiogenesis after
      chemical injury. METHODS: FHL2-LacZ knock-in mice were used to trace FHL2 gene
      expression before and after corneal injury. Corneal angiogenesis between FHL2
      null mice and wild-type mice that underwent chemical and mechanical denudation of
      corneal and limbal epithelium were compared. New growth vessel density was
      assessed by CD31 staining and was analyzed using image analysis software. Levels
      of vascular endothelial growth factor (VEGF) and cyclooxygenase (COX)-2 proteins
      were determined by Western blot assay. RESULTS: beta-Galactosidase staining of
      corneal tissue in FHL2-LacZ knock-in mice revealed that FHL2 gene expression is
      upregulated in the corneal epithelium after corneal injury. Ten days after
      injury, corneal neovascularization was observed in control and FHL2-null mice.
      New corneal vessel density was found to be lower in the FHL2-null mice injury
      group than in the wild-type mice injury group. Western blot analysis showed that
      VEGF and COX-2 protein levels were higher after chemical injury in FHL2-null mice
      and wild-type mice. However, the upregulated VEGF protein was significantly lower
      in the FHL2-null mice than in the wild-type mice. CONCLUSIONS: The decreased
      chemical-induced corneal angiogenesis found in the FHL2-null mice in this study
      indicated that FHL2 protein plays a role in inhibiting inflammatory angiogenesis.

PMID- 18708620
TI  - The transcription factor gene FOXC1 exhibits a limited role in primary congenital
      glaucoma.
AB  - PURPOSE: Primary congenital glaucoma (PCG) is an autosomal recessive disorder
      that has been linked to CYP1B1 mutations. This study was conducted to explore the
      role of FOXC1, which is involved in anterior segment dysgenesis, in PCG. METHODS:
      An earlier screening for CYP1B1 in a clinically well-characterized PCG cohort (n
      = 301) revealed cases that were either homozygous (n = 73), compound heterozygous
      (n = 18), or heterozygous (n = 41) for the mutant allele, whereas the remaining
      (n = 169) did not harbor any mutation. Hence, FOXC1 was screened in 210 PCG cases
      who were either heterozygous (n = 41) or did not harbor any CYP1B1 mutation (n =
      169), along with ethnically matched normal control subjects (n = 157) by
      resequencing the entire coding region. RESULTS: Two heterozygous missense (H128R
      and C135Y) and three frame shift mutations (g.1086delC, g.1155del9bp, and
      g.1947dup25bp) were observed in FOXC1 in 5 (2.38%) of 210 cases. The missense
      mutations had a de novo origin in two sporadic cases, whereas the FOXC1 deletions
      were seen in two cases that were also heterozygous for the CYP1B1 allele (R368H).
      The parents of the proband with g.1086delC were heterozygous for either the FOXC1
      or CYP1B1 alleles. The unaffected mother of the proband with the g.1155del9bp was
      heterozygous for both the FOXC1 and CYP1B1 alleles; the father harbored only the
      FOXC1 allele. Familial segregation of the g.1947dup25bp could not be performed
      because of the unavailability of DNA from one parent. Except for the g.1155del9bp
      (0.95% normal chromosomes), all the other variations were absent in the control
      subjects. CONCLUSIONS: The present study indicates a limited role of FOXC1 in PCG
      pathogenesis.

PMID- 18708621
TI  - Observation of erythrocyte dynamics in the retinal capillaries and
      choriocapillaris using ICG-loaded erythrocyte ghost cells.
AB  - PURPOSE: To find evidence of retinal vasomotion and to examine the relationship
      between erythrocyte dynamics and previously observed high-frequency pulsatile
      blood flow through the choriocapillaris. METHODS: An osmotic shock technique was
      used to encapsulate indocyanine green (ICG) dye in erythrocyte ghost cells at a
      concentration that produced maximum cell fluorescence. By obviating the plasma
      staining that results from aqueous ICG's high affinity for plasma proteins, high
      contrast was maintained between reinjected ICG-loaded erythrocytes and their
      plasma background. High-speed, high-magnification ICG angiograms showing
      individual cell movement were recorded from the intact eyes of four monkeys and
      three rabbits for periods up to 30 seconds. RESULTS: In monkey retinal perifoveal
      capillaries, numerous erythrocytes were seen to pause for as long as 20 seconds
      and then resume transit. Similar pausing behavior was observed in the subfoveal
      choriocapillaris. Individual erythrocytes also were seen to pause in the rabbits'
      choriocapillaries below the medullary rays, where visualization of the cells was
      uninhibited by overlying retinal vasculature or dense pigment. CONCLUSIONS:
      Reinjected ICG-loaded erythrocytes permit routine visualization of retinal
      capillary and choriocapillaris hemodynamics of the intact eye. It is speculated
      that erythrocyte-pausing in both microcirculations facilitates metabolic exchange
      across capillary walls. In retinal capillaries, pausing is presumed to result
      from vasomotion-which has been postulated as necessary for the inhibition of
      retinal edema-and in choriocapillaries, to result from the shifting distributions
      of local perfusion pressures within the network of capillary vessel segments that
      comprise each lobular area of the choriocapillaris vascular plexus.

PMID- 18708623
TI  - Relationship of the optical coherence tomography signal to underlying retinal
      histology in the tree shrew (Tupaia belangeri).
AB  - PURPOSE: To interpret the retinal origin of the optical coherence tomography
      (OCT) signal by objectively (i.e., minimal investigator bias) aligning in vivo
      OCT longitudinal reflectivity profiles (LRPs) with corresponding vertical
      histologic sections. METHODS: The Zeiss StratusOCT system was used to obtain
      retinal B-scans in vivo in eyes from adult tree shrews. Subsequently, the retinas
      were fixed and embedded. Semithin vertical sections through the retina were
      obtained from the same locations as the LRPs. A statistical correlation procedure
      that accounted for axial tissue shrinkage determined the best relationship
      between features in the LRP and sublaminae boundaries in corresponding histology
      sections. RESULTS: For the optimal relationship, the three regions of high
      reflectivity in the inner OCT signal corresponded to (1) the nerve fiber and
      ganglion cell layers, (2) the inner plexiform layer and amacrine cell somas, and
      (3) the outer plexiform layer. The two regions of low reflectivity in the inner
      OCT signal corresponded to (1) the somas of Muller, bipolar, and horizontal cells
      in the inner nuclear layer and (2) the outer nuclear layer. The outer OCT signal
      had a region of high reflectivity that corresponded to the photoreceptor inner
      and outer segments, the pigment epithelium, Bruch's membrane, and at least part
      of the choriocapillaris. CONCLUSIONS: These results provide a clear
      interpretation for the OCT signal in terms of the underlying retinal anatomy.
      This interpretation can be used in vivo to identify sublaminae affected by
      retinal disease and has implications for the origin of the inner OCT signal in
      human retina.

PMID- 18708622
TI  - Effects of long-term administration of 9-cis-retinyl acetate on visual function
      in mice.
AB  - PURPOSE: Long-term effects of treatment with 9-cis-retinyl acetate (9-cis-R-Ac),
      an artificial retinoid prodrug, were tested on changes in rod and cone visual
      functions in mice. METHODS: The acetyl ester of the functional geometric
      chromophore 9-cis-retinal was delivered by oral gavage to C57BL/6 female mice. In
      initial experiments, 10-month-old mice were used for the single treatment with 9
      cis-R-Ac or the control vehicle. In long-term experiments, 4-month-old mice were
      treated with 9-cis-R-Ac monthly for 6 and 10 months. Photoreceptor status was
      evaluated by various electroretinographic (ERG) techniques, retinoid analyses,
      and retinal morphology. Opsin, the predicted target of oxidized 9-cis-R-Ac, was
      purified and its chromophore was characterized. RESULTS: Age-related changes
      observed in vehicle-treated mice at 10 months of age, compared with those in 4
      month-old mice, included a progressive decline in ERG responses, such as a
      decreased rate of dark adaptation and a lowered rhodopsin/opsin ratio.
      Administration of 9-cis-R-Ac increased the rhodopsin regeneration ratio, and
      improved ERG responses and dark adaptation. Compared with vehicle-treated control
      animals, 10- and 14-month-old mice treated monthly with 9-cis-R-Ac for 6 or 10
      months exhibited improved dark adaptation. In 14-month-old mice treated monthly,
      changes in the expression of retina-specific genes in the eye were detected by
      mRNA expression profiling, but no significant effects in gene expression were
      detected in the liver and kidney. CONCLUSIONS: Deteriorating photoreceptor
      function documented in mice at 10 and 14 versus 4 months of age was improved
      significantly by long-term, monthly administration of 9-cis-R-Ac. These findings
      suggest a potential therapeutic approach to prevent age-related retinal
      dysfunction.

PMID- 18708624
TI  - Mature enzymatic collagen cross-links, hydroxylysylpyridinoline and
      lysylpyridinoline, in the aging human vitreous.
AB  - PURPOSE: The vitreous body of the human eye undergoes progressive morphologic
      changes with aging. Since the enzymatic collagen cross-links
      hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are known to be
      important for the integrity of the collagen matrix, the presence in the vitreous
      on aging was studied. METHODS: Vitreous bodies (VBs; n = 143) from 119 donors
      (age 4-80 years; mean +/- SD, 54.3 +/- 17.0 years) were carefully dissected.
      After weighing and freeze-drying, all samples were analyzed by high performance
      liquid chromatography. Left and right eyes of 24 donors were compared and, for
      age-related phenomena, 119 single eyes were used. RESULTS: Within one donor, no
      significant differences were found between left and right eyes. On aging, VB wet
      weight (4.42 +/- 0.84 g) accumulates until 35 years and decreases thereafter.
      Collagen content (0.30 +/- 0.14 mg), HP per triple helix (TH; 0.55 +/- 0.18), and
      (HP plus LP)/TH (0.61 +/- 0.19) increase until 50 years followed by a decrease,
      whereas LP/TH (0.057 +/- 0.018) accumulates until 50 years and remains constant
      thereafter. The ratio between HP and LP (range, 0.42-31.0; median, 10.0) is
      constant over time. CONCLUSIONS: The accumulation of enzymatic collagen cross
      links until 50 years is consistent with collagen maturation and possible collagen
      synthesis in the human vitreous body. The decline of collagen cross-links after
      50 years is consistent with collagen breakdown.

PMID- 18708626
TI  - Slow-releasing paclitaxel in polytetrafluoroethylene/polylactide-co-glycolide
      laminate delays adjustment after strabismus surgery in rabbit model.
AB  - PURPOSE: To determine the usefulness of slow-releasing paclitaxelin
      polytetrafluoroethylene/polylactide-co-glycolide (PTFE/PLGA) laminate for delayed
      adjustable strabismus surgery. METHODS: A prospective, masked-observer,
      controlled study was performed in 25 rabbits. Fifty rabbit eyes were divided
      randomly into three groups. After recession of the superior rectus muscle (SRM),
      a PTFE/PLGA laminate containing paclitaxel, PTFE alone, or physiologic saline was
      applied beneath and over the SRM in the PTFE/PLGA-paclitaxel group (group
      paclitaxel), the PTFE group (group PTFE), and the control group, respectively.
      Delayed adjustment was performed by a masked observer once on each SRM at 3 or 5
      weeks after surgery. Adjustability, adjustment lengths, forces required, and
      adhesion degrees were evaluated. RESULTS: In the control group, adjustment was
      impossible in any eye at 3 or 5 weeks after surgery. In group PTFE, adjustment
      was possible in 5 of 8 eyes at 3 weeks after surgery and in 5 of 10 eyes at 5
      weeks after surgery. In group paclitaxel, adjustment was possible in 6 of 9 eyes
      and in 7 of 7 eyes at 3 and 5 weeks after surgery. On comparing adjustability, a
      significant difference was observed between group paclitaxel and the control
      group at 3 and 5 weeks after surgery (P = 0.016 and P = 0.001, respectively). A
      significant difference was observed between group paclitaxel and the control
      group (P = 0.003) in terms of adhesion between SRMs and sclera 5 weeks after
      surgery. CONCLUSIONS: Slow-releasing paclitaxel in PTFE/PLGA was found to reduce
      adhesion and allowed delayed adjustment in most eyes for up to 5 weeks after
      surgery.

PMID- 18708625
TI  - Changes in ferritin H- and L-chains in canine lenses with age-related nuclear
      cataract.
AB  - PURPOSE: To determine potential differences in the characteristics of the iron
      storage protein ferritin and its heavy (H) and light (L) subunits in fiber cells
      from cataractous and noncataractous lenses of older dogs. METHODS: Lens fiber
      cell homogenates were analyzed by SDS-PAGE, and ferritin chains were
      immunodetected with ferritin chain-specific antibodies. Ferritin concentration
      was measured by ELISA. Immunohistochemistry was used to localize ferritin chains
      in lens sections. RESULTS: The concentration of assembled ferritin was comparable
      in noncataractous and cataractous lenses of similarly aged dogs. The ferritin L
      chain detected in both lens types was modified and was approximately 11 kDa
      larger (30 kDa) than standard L-chain (19 kDa) purified from canine liver. The H
      chain identified in cataractous fiber cells (29 kDa) differed from the 21-kDa
      standard canine H-chain and from the 12-kDa modified H-chain present in fiber
      cells of noncataractous lenses. Histologic analysis revealed that the H-chain was
      distributed differently throughout cataractous lenses compared with
      noncataractous lenses. There was also a difference in subunit makeup of assembled
      ferritin between the two lens types. Ferritin from cataractous lenses contained
      more H-chain and bound 11-fold more iron than ferritin from noncataractous
      lenses. CONCLUSIONS: There are significant differences in the characteristics of
      ferritin H-chain and its distribution in canine cataractous lenses compared with
      noncataractous lenses. The higher content of H-chain in assembled ferritin allows
      this molecule to sequester more iron. In addition, the accumulation of H-chain in
      deeper fiber layers of the lens may be part of a defense mechanism by which the
      cataractous lens limits iron-catalyzed oxidative damage.

PMID- 18708627
TI  - LX211 (voclosporin) suppresses experimental uveitis and inhibits human T cells.
AB  - PURPOSE: To test the therapeutic effectiveness of voclosporin against
      experimental autoimmune uveoretinitis (EAU) in rats and to evaluate its effect on
      human T cells. METHODS: EAU was induced by immunization with a uveitogenic
      protein. Voclosporin administration, by subcutaneous injection, began on day (d)
      0 or d7 after immunization. Treatment effectiveness was evaluated in vivo using
      clinical EAU scoring (d7-d13) and histopathologic evaluation of enucleated eyes
      after experimental termination. Rodent lymphocytes were harvested from lymph
      nodes on d14 for antigen-specific proliferation assays. The effect of voclosporin
      on human T-cell proliferation and cytokine secretion was examined in vitro.
      RESULTS: Voclosporin prevented EAU development in rats receiving medium and high
      preventive doses, whereas high-dose voclosporin administration effectively
      treated EAU. Lymphocytes from animals treated with voclosporin had decreased
      antigen-specific proliferation in vitro compared with lymphocytes from untreated
      animals. No evidence of abnormal ocular histopathology was found in the eyes from
      animals that received high doses of therapeutic voclosporin. Using human T cells,
      voclosporin inhibited human T-cell proliferation up to 100-fold. Furthermore,
      voclosporin treatment of human T cells significantly reduced pan T-cell effector
      responses. CONCLUSIONS: Voclosporin effectively suppressed uveoretinitis in an
      animal model that imitates the human inflammatory ocular disease by inhibiting
      lymphocyte proliferation. In addition, voclosporin effectively inhibited human T
      cell proliferation and function in vitro. The authors report the first evidence
      supporting the application of voclosporin to treat intraocular inflammation.

PMID- 18708628
TI  - Overexpression of TOSO in CLL is triggered by B-cell receptor signaling and
      associated with progressive disease.
AB  - Resistance toward apoptotic stimuli mediated by overexpression of antiapoptotic
      factors or extracellular survival signals is considered to be responsible for
      accumulation of malignant B cells in chronic lymphocytic leukemia (CLL). TOSO was
      identified as overexpressed candidate gene in CLL, applying unit-transformation
      assays of publicly available microarray datasets. Based on CLL samples from 106
      patients, TOSO was identified to exhibit elevated relative expression (RE) of 6.8
      compared with healthy donor B cells using quantitative real-time polymerase chain
      reaction (PCR; P = .004). High levels of TOSO expression in CLL correlated with
      high leukocyte count, advanced Binet stage, previous need for chemotherapy, and
      unmutated IgV(H) status. CD38(+) CLL subsets harboring proliferative activity
      showed enhanced TOSO expression. We evaluated functional mechanisms of aberrant
      TOSO expression and identified TOSO expression significantly induced by B-cell
      receptor (BCR) stimulation compared with control cells (RE; 8.25 vs 4.86; P =
      .01). In contrast, CD40L signaling significantly reduced TOSO expression (RE,
      2.60; P = .01). In summary, we show that the antiapoptotic factor TOSO is
      associated with progressive disease and enhanced in the proliferative CD38(+) CLL
      subset. Both association with unmutated IgV(H) and the specific induction of TOSO
      via the BCR suggest autoreactive BCR signaling as a key mediator of apoptosis
      resistance in CLL.

PMID- 18708629
TI  - AL amyloidosis associated with IgM paraproteinemia: clinical profile and
      treatment outcome.
AB  - AL amyloidosis associated with immunoglobulin M (IgM) paraproteinemia is rare. We
      report 103 consecutive such patients evaluated at the National Amyloidosis Centre
      (London, United Kingdom) between 1988 and 2006. Renal, cardiac, and lymph node
      amyloid was present in 53%, 35%, and 21% of patients, respectively, at
      presentation and 2 or more organs were involved in 54%. Seventy-three percent had
      an abnormal bone marrow infiltrate (lymphoid in 87%). The median IgM paraprotein
      was 8 g/L and serum free light chain (FLC) ratio was abnormal in 77 (88%) of 87.
      The abnormal FLC component was more than 100 mg/L in only 31% cases. Thirty-two
      percent achieved a partial hematologic response to treatment with no complete
      responders, and there appeared to be a greater response to combination regimens
      than single-agent oral alkylators (59% vs 20%, respectively; P = .003). Four
      achieved amyloidotic organ responses; organ function remained stable in 68%. None
      with lymph node involvement showed nodal improvement. Median overall survival was
      49 months. AL amyloidosis with IgM paraproteinemia represents a distinctive
      subset of patients with AL amyloidosis who have a wider variety of underlying
      clonal disorders (often lymphoid) than AL in general, have low-level FLC
      abnormality, and should be treated with appropriately tailored chemotherapeutic
      regimens for the underlying clonal disorder.

PMID- 18708630
TI  - Usefulness of pressure-controlled ventilation at high inspiratory pressures to
      induce acute lung injury in mice.
AB  - Acute lung injury (ALI), as occurs with prolonged mechanical ventilation,
      contributes to morbidity and mortality of critical illness, and studies on novel
      genetic or pharmacological targets are areas of intense investigation. Here, we
      systematically tested a murine model of ALI by using pressure-controlled
      ventilation to induce ventilator-induced lung injury. For this purpose, C57BL/6
      or Sv129 mice were anesthetized and underwent tracheotomy followed by induction
      of ALI via mechanical ventilation. Mice were ventilated in a pressure-controlled
      setting at different inspiratory pressure levels (15-45 mbar) and over different
      times (0-90 min, 100% oxygen). As outcome parameters, we assessed pulmonary edema
      (wet-to-dry ratios), bronchoalveolar fluid albumin content, pulmonary
      myeloperoxidase activity, macrophage inflammatory protein-2, and pulmonary gas
      exchange. These studies revealed maximal differences in severity of lung injury
      between different mouse strains after 90 min of ventilation time at 45 mbar. Use
      of lower concentrations of inspired oxygen did not alter disease severity.
      Increases of CD73 transcript (5'-ectonucleotidase, pacemaker of extracellular
      adenosine production) or total pulmonary adenosine levels with mechanical
      ventilation were less pronounced in C57BL/6 mice, suggesting attenuated adenosine
      protection in C57BL/6 mice. Together, these studies demonstrate feasibility of
      this model to induce murine ALI.

PMID- 18708631
TI  - Prednisolone inhibits PDGF-induced nuclear translocation of NF-kappaB in human
      pulmonary artery smooth muscle cells.
AB  - Pulmonary vascular remodeling, a major cause for the elevated pulmonary vascular
      resistance in patients with pulmonary arterial hypertension (PAH), is partially
      due to increased proliferation of pulmonary arterial smooth muscle cells (PASMC)
      in the media, resulting in vascular wall thickening. Platelet-derived growth
      factor (PDGF) is a potent mitogen that may be involved in the progression of PAH.
      Blockade of PDGF receptors has been demonstrated to have therapeutic potential
      for patients with severe pulmonary hypertension. Prednisolone is an
      immunosuppressant shown to have anti-inflammatory and antiproliferative effects
      on PASMC. This study was designed to investigate whether PDGF and prednisolone
      affect human PASMC proliferation by regulating the nuclear translocation of NF
      kappaB (a transcription factor composed of 2 subunits, p50 and p65). Treatment of
      human PASMC with PDGF (10 ng/ml) significantly increased nuclear translocation of
      p50 and p65 subunits. Inhibition of NF-kappaB activation or nuclear translocation
      of p50/p65 significantly attenuated PDGF-induced PASMC proliferation (determined
      by [(3)H]thymidine incorporation). In the presence of prednisolone (200 microM),
      the PDGF-induced nuclear translocation of p50 and p65 subunits was markedly
      inhibited (P < 0.05 vs. the cells treated with PDGF alone). These results
      indicate that PDGF-induced nuclear translocation of NF-kappaB may play an
      important role in stimulating PASMC proliferation (and/or enhancing PASMC
      survival), whereas prednisolone may exert anti-inflammatory and antiproliferative
      effects on PASMC by inhibiting NF-kappaB nuclear translocation.

PMID- 18708632
TI  - Mitigation of chlorine-induced lung injury by low-molecular-weight antioxidants.
AB  - Chlorine (Cl(2)) is a highly reactive oxidant gas used extensively in a number of
      industrial processes. Exposure to high concentrations of Cl(2) results in acute
      lung injury that may either resolve spontaneously or progress to acute
      respiratory failure. Presently, the pathophysiological sequelae associated with
      Cl(2)-induced acute lung injury in conscious animals, as well as the cellular and
      biochemical mechanisms involved, have not been elucidated. We exposed conscious
      Sprague-Dawley rats to Cl(2) gas (184 or 400 ppm) for 30 min in environmental
      chambers and then returned them to room air. At 1 h after exposure, rats showed
      evidence of arterial hypoxemia, respiratory acidosis, increased levels of
      albumin, IgG, and IgM in bronchoalveolar lavage fluid (BALF), increased BALF
      surfactant surface tension, and significant histological injury to airway and
      alveolar epithelia. These changes were more pronounced in the 400-ppm-exposed
      rats. Concomitant decreases of ascorbate (AA) and reduced glutathione (GSH) were
      also detected in both BALF and lung tissues. In contrast, heart tissue AA and GSH
      content remained unchanged. These abnormalities persisted 24 h after exposure in
      rats exposed to 400 ppm Cl(2). Rats injected systemically with a mixture of AA,
      deferoxamine, and N-acetyl-L-cysteine before exposure to 184 ppm Cl(2) had normal
      levels of AA, lower levels of BALF albumin and normal arterial Po(2) and Pco(2)
      values. These findings suggest that Cl(2) inhalation damages both airway and
      alveolar epithelial tissues and that resulting effects were ameliorated by
      prophylactic administration of low-molecular-weight antioxidants.

PMID- 18708633
TI  - Role of P63 (CKAP4) in binding of surfactant protein-A to type II pneumocytes.
AB  - We have recently described a putative receptor for lung surfactant protein-A (SP
      A) on rat type II pneumocytes. The receptor, P63, is a 63-kDa type II
      transmembrane protein. Coincubation of type II cells with P63 antibody (Ab)
      reversed the inhibitory effect of SP-A on secretagogue-stimulated surfactant
      secretion from type II cells. To further characterize SP-A interactions with P63,
      we expressed recombinant P63 protein in Escherichia coli and generated antibodies
      to P63. Immunogold electron microscopy confirmed endoplasmic reticulum and plasma
      membrane localization of P63 in type II cells with prominent labeling of
      microvilli. Binding characteristics of iodinated SP-A to type II cells in the
      presence of P63 Ab were determined. Binding (4 degrees C, 1 h) of (125)I-SP-A to
      type II cells demonstrated both specific (calcium-dependent) and nonspecific
      (calcium-independent) components. Ab to P63 protein blocked the specific binding
      of (125)I-SP-A to type II cells and did not change the nonspecific SP-A
      association. A549 cells, a pneumocyte model cell line, expressed substantial
      levels of P63 and demonstrated specific binding of (125)I-SP-A that was inhibited
      by the P63 Ab. The secretagogue (cAMP)-stimulated increase in calcium-dependent
      binding of SP-A to type II cells was blocked by the presence of P63 Ab.
      Transfection of type II cells with small interfering RNA to P63 reduced P63
      protein expression, attenuated P63-specific SP-A binding, and reversed the
      ability of SP-A to prevent surfactant secretion from the cells. Our results
      further substantiate the role of P63 as an SP-A receptor protein localized on the
      surface of lung type II cells.

PMID- 18708634
TI  - Mechanical strain of alveolar type II cells in culture: changes in the
      transcellular cytokeratin network and adaptations.
AB  - Mechanical forces exert multiple effects in cells, ranging from altered protein
      expression patterns to cell damage and death. Despite undisputable biological
      importance, little is known about structural changes in cells subjected to strain
      ex vivo. Here, we undertake the first transmission electron microscopy
      investigation combined with fluorescence imaging on pulmonary alveolar type II
      cells that are subjected to equibiaxial strain. When cells are investigated
      immediately after stretch, we demonstrate that curved cytokeratin (CK) fibers are
      straightened out at 10% increase in cell surface area (CSA) and that this is
      accompanied by a widened extracellular gap of desmosomes-the insertion points of
      CK fibers. Surprisingly, a CSA increase by 20% led to higher fiber curvatures of
      CK fibers and a concurrent return of the desmosomal gap to normal values. Since
      20% CSA increase also induced a significant phosphorylation of CK8-ser431, we
      suggest CK phosphorylation might lower the tensile force of the transcellular CK
      network, which could explain the morphological observations. Stretch durations of
      5 min caused membrane injury in up to 24% of the cells stretched by 30%, but the
      CK network remained surprisingly intact even in dead cells. We conclude that CK
      and desmosomes constitute a strong transcellular scaffold that survives cell
      death and hypothesize that phosphorylation of CK fibers is a mechano-induced
      adaptive mechanism to maintain epithelial overall integrity.

PMID- 18708635
TI  - Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P
      like headgroup interactions.
AB  - Strong evidence exists for interactions of zwitterionic phosphate and amine
      groups in sphingosine-1 phosphate (S1P) to conserved Arg and Glu residues present
      at the extracellular face of the third transmembrane domain of S1P receptors. The
      contribution of Arg(120) and Glu(121) for high-affinity ligand-receptor
      interactions is essential, because single-point R(120)A or E(121)A S1P(1) mutants
      neither bind S1P nor transduce S1P function. Because S1P receptors are
      therapeutically interesting, identifying potent selective agonists with different
      binding modes and in vivo efficacy is of pharmacological importance. Here we
      describe a modestly water-soluble highly selective S1P(1) agonist [2-(4-(5-(3,4
      diethoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl amino) ethanol
      (CYM-5442)] that does not require Arg(120) or Glu(121) residues for activating
      S1P(1)-dependent p42/p44 mitogen-activated protein kinase phosphorylation, which
      defines a new hydrophobic pocket in S1P(1). CYM-5442 is a full agonist in vitro
      for S1P(1) internalization, phosphorylation, and ubiquitination. It is noteworthy
      that CYM-5442 was a full agonist for induction and maintenance of S1P(1)
      dependent blood lymphopenia, decreasing B lymphocytes by 65% and T lymphocytes by
      85% of vehicle. Induction of CYM-5442 lymphopenia was dose- and time-dependent,
      requiring serum concentrations in the 50 nM range. In vitro measures of S1P(1)
      activation by CYM-5442 were noncompetitively inhibited by a specific S1P(1)
      antagonist [(R)-3-amino-(3-hexylphenylamino)-4-oxobutylphosphonic acid (W146)],
      competitive for S1P, 2-amino-2-(4-octylphenethyl)propane-1,3-diol (FTY720-P), and
      5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-3-[3-(trifluoromethyl)phenyl]-1,2, 4
      oxadiazole (SEW2871). In addition, lymphopenia induced by CYM-5442 was reversed
      by W146 administration or upon pharmacokinetic agonist clearance.
      Pharmacokinetics in mice also indicated that CYM-5442 partitions significantly in
      central nervous tissue. These data show that CYM-5442 activates S1P(1)-dependent
      pathways in vitro and to levels of full efficacy in vivo through a hydrophobic
      pocket separate from the orthosteric site of S1P binding that is headgroup
      dependent.

PMID- 18708636
TI  - The redox environment in the mitochondrial intermembrane space is maintained
      separately from the cytosol and matrix.
AB  - Redox control in the mitochondrion is essential for the proper functioning of
      this organelle. Disruption of mitochondrial redox processes contributes to a host
      of human disorders, including cancer, neurodegenerative diseases, and aging. To
      better characterize redox control pathways in this organelle, we have targeted a
      green fluorescent protein-based redox sensor to the intermembrane space (IMS) and
      matrix of yeast mitochondria. This approach allows us to separately monitor the
      redox state of the matrix and the IMS, providing a more detailed picture of redox
      processes in these two compartments. To verify that the sensors respond to
      localized glutathione (GSH) redox changes, we have genetically manipulated the
      subcellular redox state using oxidized GSH (GSSG) reductase localization mutants.
      These studies indicate that redox control in the cytosol and matrix are
      maintained separately by cytosolic and mitochondrial isoforms of GSSG reductase.
      Our studies also demonstrate that the mitochondrial IMS is considerably more
      oxidizing than the cytosol and mitochondrial matrix and is not directly
      influenced by endogenous GSSG reductase activity. These redox measurements are
      used to predict the oxidation state of thiol-containing proteins that are
      imported into the IMS.

PMID- 18708637
TI  - Processing mutations disrupt interactions between the nucleotide binding and
      transmembrane domains of P-glycoprotein and the cystic fibrosis transmembrane
      conductance regulator (CFTR).
AB  - P-glycoprotein (P-gp, ABCB1) is an ATP-dependent drug pump. Each of its two
      homologous halves contains a transmembrane domain (TMD) that has six
      transmembrane (TM) segments and a nucleotide-binding domain (NBD). Determining
      how the two halves interact may provide insight into the folding of P-gp as the
      drug-binding pocket and nucleotide-binding sites are predicted to be at the
      interface between the two halves. Here, we present evidence for NBD1-TMD2 and
      NBD2-TMD1 interactions. We also show that TMD-NBD interactions in immature and
      mature P-gp can be affected by the presence of a processing mutation. We found
      that the NBD-TMD mutants L443C(NBD1)/S909C(TMD2) and A266C(TMD1)/F1086C(NBD2)
      could be cross-linked at 0 degrees C with oxidant (copper phenanthroline). Cross
      linking was inhibited by vanadate-trapping of nucleotide. The presence of a
      processing mutation (G268V/L443C(NBD1)/S909C(TMD2);
      L1260A/A266C(TMD1)/F1086C(NBD2)) resulted in the synthesis of the immature (150
      kDa) protein as the major product and the mutants could not be cross-linked with
      copper phenanthroline. Expression of the processing mutants in the presence of a
      pharmacological chaperone (cyclosporin A), however, resulted in the expression of
      mature (170 kDa) protein at the cell surface that could be cross-linked.
      Similarly, CFTR mutants A274C(TMD1)/L1260C(NBD2) and V510C(NBD1)/A1067C(TMD2)
      could be cross-linked at 0 degrees C with copper phenanthroline. Introduction of
      DeltaF508 mutation in these mutants, however, resulted in the synthesis of
      immature CFTR that could not be cross-linked. These results suggest that
      establishment of NBD interactions with the opposite TMD is a key step in folding
      of ABC transporters.

PMID- 18708639
TI  - Tools and strategies for the reduction of inappropriate implantable cardioverter
      defibrillator shocks.
AB  - Implantable cardioverter defibrillators (ICDs) have been shown to provide a
      survival benefit in patients at high risk of sudden cardiac death. A major
      problem associated with ICD therapy is the occurrence of inappropriate shocks
      which impair patients' quality of life and may also be arrhythmogenic. Despite
      recent technological advances, the incidence of inappropriate shocks remains
      high, thus posing a challenge that we have to meet. In the present review we
      summarise the available tools and the strategies that can be followed in order to
      reduce inappropriate ICD shocks.

PMID- 18708638
TI  - Functional characterization of the N-terminal domain of subunit H (Vma13p) of the
      yeast vacuolar ATPase.
AB  - The yeast Saccharomyces cerevisiae vacuolar H(+)-ATPase (V-ATPase) is a
      multisubunit complex responsible for acidifying intracellular organelles and is
      highly regulated. One of the regulatory subunits, subunit H, is encoded by the
      VMA13 gene in yeast and is composed of two domains, the N-terminal domain (amino
      acids (aa) 1-352) and the C-terminal domain (aa 353-478). The N-terminal domain
      is required for the activation of the complex, whereas the C-terminal domain is
      required for coupling ATP hydrolysis to proton translocation (Liu, M., Tarsio,
      M., Charsky, C. M., and Kane, P. M. (2005) J. Biol. Chem. 280, 36978-36985).
      Experiments with epitope-tagged copies of Vma13p revealed that there is only one
      copy of Vma13p/subunit H per V-ATPase complex. Analysis of the N-terminal domain
      shows that the first 179 amino acids are not required for the activation and full
      function of the V-ATPase complex and that the minimal region of Vma13p/subunit H
      capable of activating the V-ATPase is aa 180-353 of the N-terminal domain.
      Subunit H is expressed as two splice variants in mammals, and deletion of 18
      amino acids in yeast Vma13p corresponding to the mammalian subunit H beta isoform
      results in reduced V-ATPase activity and significantly lower coupling of ATPase
      hydrolysis to proton translocation. Intriguingly, the yeast Vma13p mimicking the
      mammalian subunit H beta isoform is functionally equivalent to Vma13p lacking the
      entire C-terminal domain. These results suggest that the mammalian V-ATPase
      complexes with subunit H splice variant SFD-alpha or SFD-beta are likely to have
      different activities and may perform distinct cellular functions.

PMID- 18708640
TI  - Adrenomedullin induces lymphangiogenesis and ameliorates secondary lymphoedema.
AB  - AIMS: Adrenomedullin (AM) is a multifunctional peptide hormone that plays a
      significant role in vasodilation and angiogenesis. Lymphoedema is a common but
      refractory disorder that is difficult to be treated with conventional therapy. We
      therefore investigated whether AM promotes lymphangiogenesis and improves
      lymphoedema. METHODS AND RESULTS: The effects of AM on lymphatic endothelial
      cells (LEC) were investigated. AM promoted proliferation, migration, and network
      formation of cultured human lymphatic microvascular endothelial cells (HLMVEC).
      AM increased intracellular cyclic adenosine monophosphate (cAMP) level in HLMVEC.
      The cell proliferation induced by AM was inhibited by a cAMP antagonist and
      mitogen-activated protein kinase kinase (MEK) inhibitors. Phosphorylated
      extracellular signal-regulated kinase (ERK) in HLMVEC was increased by AM.
      Continuous administration of AM (0.05 microg/kg/min) to BALB/c mice with tail
      lymphoedema resulted in a decrease in lymphoedema thickness. AM treatment
      increased the number of lymphatic vessels and blood vessels in the injury site.
      CONCLUSION: AM promoted LEC proliferation at least in part through the
      cAMP/MEK/ERK pathway, and infusion of AM induced lymphangiogenesis and improved
      lymphoedema in mice.

PMID- 18708641
TI  - Crassulacean acid metabolism and fitness under water deficit stress: if not for
      carbon gain, what is facultative CAM good for?
AB  - BACKGROUND: In obligate Crassulacean acid metabolism (CAM), up to 99 % of CO(2)
      assimilation occurs during the night, therefore supporting the hypothesis that
      CAM is adaptive because it allows CO(2) fixation during the part of the day with
      lower evaporative demand, making life in water-limited environments possible. By
      comparison, in facultative CAM (inducible CAM, C(3)-CAM) and CAM-cycling plants
      drought-induced dark CO(2) fixation may only be, with few exceptions, a small
      proportion of C(3) CO(2) assimilation in watered plants and occur during a few
      days. From the viewpoint of survival the adaptive advantages, i.e. increased
      fitness, of facultative CAM and CAM-cycling are not obvious. Therefore, it is
      hypothesized that, if it is to increase fitness, CAM must aid in reproduction.
      Scope An examination of published reports of 23 facultative CAM and CAM-cycling
      species finds that, in 19 species, drought-induced dark CO(2) fixation represents
      on average 11 % of C(3) CO(2) assimilation of watered plants. Evidence is
      discussed on the impact of the operation of CAM in facultative and CAM-cycling
      plants on their survival--carbon balance, water conservation, water absorption,
      photo-protection of the photosynthetic apparatus--and reproductive effort. It is
      concluded that in some species, but not all, facultative and cycling CAM
      contribute, rather than to increase carbon balance, to increase water-use
      efficiency, water absorption, prevention of photoinhibition and reproductive
      output.

PMID- 18708642
TI  - Review of wheat improvement for waterlogging tolerance in Australia and India:
      the importance of anaerobiosis and element toxicities associated with different
      soils.
AB  - BACKGROUND AND AIMS: The lack of knowledge about key traits in field environments
      is a major constraint to germplasm improvement and crop management because
      waterlogging-prone environments are highly diverse and complex, and the
      mechanisms of tolerance to waterlogging include a large range of traits. A model
      is proposed that waterlogging tolerance is a product of tolerance to anaerobiosis
      and high microelement concentrations. This is further evaluated with the aim of
      prioritizing traits required for waterlogging tolerance of wheat in the field.
      METHODS: Waterlogging tolerance mechanisms of wheat are evaluated in a range of
      diverse environments through a review of past research in Australia and India;
      this includes selected soils and plant data, including plant growth under
      waterlogged and drained conditions in different environments. Measurements focus
      on changes in redox potential and concentrations of diverse elements in soils and
      plants during waterlogging. KEY RESULTS: (a) Waterlogging tolerance of wheat in
      one location often does not relate to another, and (b) element toxicities are
      often a major constraint in waterlogged environments. Important element
      toxicities in different soils during waterlogging include Mn, Fe, Na, Al and B.
      This is the first time that Al and B toxicities have been indicated for wheat in
      waterlogged soils in India. These results support and extend the well-known
      interactions of salinity/Na and waterlogging/hypoxia tolerance. CONCLUSIONS:
      Diverse element toxicities (or deficiencies) that are exacerbated during
      waterlogging are proposed as a major reason why waterlogging tolerance at one
      site is often not replicated at another. Recommendations for germplasm
      improvement for waterlogging tolerance include use of inductively coupled plasma
      analyses of soils and plants.

PMID- 18708643
TI  - Cambial activity and intra-annual xylem formation in roots and stems of Abies
      balsamea and Picea mariana.
AB  - BACKGROUND AND AIMS: Studies on xylogenesis focus essentially on the stem,
      whereas there is basically no information about the intra-annual growth of other
      parts of the tree. As roots strongly influence carbon allocation and tree
      development, knowledge of the dynamics of xylem production and maturation in
      roots at a short time scale is required for a better understanding of the
      phenomenon of tree growth. This study compared cambial activity and xylem
      formation in stem and roots in two conifers of the boreal forest in Canada.
      METHODS: Wood microcores were collected weekly in stem and roots of ten Abies
      balsamea and ten Picea mariana during the 2004-2006 growing seasons. Cross
      sections were cut using a rotary microtome, stained with cresyl violet acetate
      and observed under visible and polarized light. The number of cells in the
      cambial zone and in differentiation, plus the number of mature cells, was counted
      along the developing xylem. KEY RESULTS: Xylem formation lasted from the end of
      May to the end of September, with no difference between stem and roots in 2004
      2005. On the contrary, in 2006 a 1-week earlier beginning of cell differentiation
      was observed in the stem, with cell wall thickening and lignification in roots
      ending up to 22 d later than in the stem. Cell production in the stem was
      concentrated early in the season, in June, while most cell divisions in roots
      occurred 1 month later. CONCLUSIONS: The intra-annual dynamics of growth observed
      in stem and roots could be related to the different amount of cells produced by
      the cambium and the patterns of air and soil temperature occurring in spring.

PMID- 18708644
TI  - Failure of particulate bioglass to prevent experimental staphylococcal infection
      of open tibial fractures.

PMID- 18708645
TI  - Prevalence and diversity of integrons and associated resistance genes in faecal
      Escherichia coli isolates of healthy humans in Spain.
AB  - OBJECTIVES: To analyse the prevalence and diversity of integrons in faecal
      Escherichia coli isolates from healthy humans in Spain. METHODS: One hundred E.
      coli isolates were obtained in Levine agar plates from faecal samples of 100
      healthy humans during March to October 2007. Susceptibility to 16 antimicrobial
      agents was determined by the disc diffusion method. The presence and
      characterization of class 1, 2 and 3 integrons, as well as the presence of other
      antimicrobial resistance genes, were performed by PCR and DNA sequencing.
      RESULTS: Integrases associated with class 1 and/or class 2 integrons were
      identified in 29 E. coli isolates (intI1 gene in 26 isolates, intI2 in 1 isolate
      and intI1 + intI2 in 2 isolates), the remaining 71 isolates being free of these
      integrons. Seven different gene cassette arrangements were demonstrated in 27 of
      the 28 intI1-positive isolates and were as follows (number of isolates): dfrA1 +
      aadA1 (12), aadA (8), dfrA17 + aadA5 (3), dfrA7 (1), dfrA5 (1), dfrA1 (1) and
      dfrA12 + orfF + aadA2 (1). Four isolates presented defective class 1 integrons
      lacking the 3'-conserved region. The three isolates containing class 2 integrons
      harboured the dfrA1 + sat + aadA1 gene cassette array in their variable region.
      Integron-positive isolates showed higher percentages of resistance to
      streptomycin, ampicillin, tetracycline, trimethoprim, sulfamethoxazole,
      chloramphenicol and nalidixic acid than integron-negative isolates. Sixty-five
      percent of the integron-positive isolates belonged to phylogenetic groups A or D.
      CONCLUSIONS: A high prevalence of integrons was detected in faecal E. coli of
      healthy humans. Individuals in the community could be a reservoir of integron
      containing E. coli isolates.

PMID- 18708646
TI  - First report of qacG, qacH and qacJ genes in Staphylococcus haemolyticus human
      clinical isolates.
AB  - OBJECTIVES: To investigate phenotypically and genotypically the presence of MDR
      efflux pumps in 21 clinical isolates of Staphylococcus haemolyticus collected
      over a period of 10 years. METHODS: MICs of different antibiotics and biocides
      were determined by the broth dilution method in the presence/absence of carbonyl
      cyanide-m-chlorophenylhydrazone (CCCP), an efflux pump inhibitor. PCR followed by
      sequencing was performed to detect the qac genes that encode for antiseptic
      resistance. Clonal relationships were determined by PFGE SmaI patterns using a
      standard protocol. RESULTS: All the isolates were resistant to gentamicin, 15 to
      erythromycin, 18 to ciprofloxacin, 7 to chloramphenicol and 1 to tetracycline.
      They showed higher susceptibility to antibiotics when they were exposed to CCCP.
      The MICs of ethidium bromide, SDS and benzalkonium chloride were also decreased,
      whereas the MIC of triclosan was decreased in only four isolates in the presence
      CCCP. Of the 21 isolates, qacA/B was detected in 5 isolates, smr in all of the
      isolates, qacG in 11 isolates, qacH in 10 isolates and qacJ in 4 isolates. PFGE
      analysis of the 21 isolates clustered them into 14 clones at 90% similarity
      corresponding to differences of between 7 and 16 bands among the clones.
      CONCLUSIONS: The efflux mechanism seems to be an important mechanism to confer
      resistance to antibiotics and biocides through MDR pumps. It was observed that
      several qac genes coexist in some of the isolates and seem to act simultaneously
      in the removal of different compounds out of the bacterial cell. The qac genes
      are horizontally spread among different clones.

PMID- 18708647
TI  - Cancer incidence and incidence rates in Japan in 2002: based on data from 11
      population-based cancer registries.
AB  - The number of cancer incidences, crude incidence rates, age-standardized
      incidence rates in 2002 in Japan are estimated. The estimated total number of
      incidences was 570,598.

PMID- 18708649
TI  - Psychology, cardiology, and gender.

PMID- 18708648
TI  - Bile duct-bound growth of precursor cells of preneoplastic foci inducible in the
      initiation stage of rat chemical hepatocarcinogenesis by 2-acetylaminofluorene.
AB  - BACKGROUND: We previously detected precursor cell populations of preneoplastic
      foci, GST-P(+)/GGT(-) and GST-P(+)/GGT(+) minifoci, in rat liver in the
      initiation stage of chemical hepatocarcinogenesis, where GST-P and GGT represent
      glutathione S-transferase P-form and gamma-glutamyltranspeptidase, respectively.
      METHODS: Sprague-Dawley male rats were fed a basal diet containing 2
      acetylaminofluorene (0.02%) over 16 weeks. Precursor cells were detected by our
      sensitive staining method for GGT activity and immunocytochemical staining for
      GST-P. RESULTS: GST-P(+)/GGT(-) single cells were overproduced maximally in the
      animal liver after the 6 weeks followed by a gradual growth of GST-P(+)/GGT(-)
      and GST-P(+)/GGT(+) minifoci, which were bound to bile ducts and ductules. GGT
      was expressed within GST-P(+) minifoci gradually with time forming GGT(+) lane
      like structures. The bile duct binding and lane-like structure formation were
      prominent especially when minifoci-bearing rats were subjected to two-thirds
      partial hepatectomy. CONCLUSIONS: A variety of precursor minifoci were noted to
      be selectively bound to bile ducts and ductules in rat liver, which may be of
      physiologic significance in excretion of carcinogens during initiation.

PMID- 18708650
TI  - Bayesian hierarchically weighted finite mixture models for samples of
      distributions.
AB  - Finite mixtures of Gaussian distributions are known to provide an accurate
      approximation to any unknown density. Motivated by DNA repair studies in which
      data are collected for samples of cells from different individuals, we propose a
      class of hierarchically weighted finite mixture models. The modeling framework
      incorporates a collection of k Gaussian basis distributions, with the individual
      specific response densities expressed as mixtures of these bases. To allow
      heterogeneity among individuals and predictor effects, we model the mixture
      weights, while treating the basis distributions as unknown but common to all
      distributions. This results in a flexible hierarchical model for samples of
      distributions. We consider analysis of variance-type structures and a
      parsimonious latent factor representation, which leads to simplified inferences
      on non-Gaussian covariance structures. Methods for posterior computation are
      developed, and the model is used to select genetic predictors of baseline DNA
      damage, susceptibility to induced damage, and rate of repair.

PMID- 18708651
TI  - Trends in the use of intracytoplasmatic sperm injection marked variability
      between countries.
AB  - BACKGROUND: ICSI is used increasingly often compared with standard IVF. The aim
      of the present study was to analyse the changes in the use of ICSI, and discuss
      possible causes and consequences. METHODS: Data from National and Regional
      registers were analysed for trends in the use of ICSI and indications for
      assisted reproductive technology (ART). RESULTS: The use of ICSI increased from
      39.6% of ART cycles in 1997 to 58.9% in 2004 (USA 57.5%, Australia/New Zealand
      58.6%, Europe 59.3%). The Nordic countries, the Netherlands and the UK used ICSI
      to a low extent (40.0-44.3%), whereas Austria, Belgium and Germany (68.5-72.9%)
      and the southern European countries like Greece, Italy and Spain used ICSI
      frequently (66.0-81.2%). The marked increase in the proportion of ICSI cycles
      seems primarily due to an increased use in couples classified as having mixed
      causes of infertility, unexplained infertility and advanced age together with a
      relative decline in tubal factor infertility. An absolute increase in the
      prevalence of couples with impairment in semen quality remains a possibility.
      CONCLUSIONS: ICSI is used increasingly, but huge differences exist between
      countries within Europe. It is not possible to determine specific factors that
      explain the differences. As ICSI does not give higher pregnancy rates than IVF in
      couples without male factors, and as it adds additional costs, infertile couples
      and society may benefit from a less frequent use of ICSI in some countries.

PMID- 18708652
TI  - Specific tumour-associated methylation in normal human term placenta and first
      trimester cytotrophoblasts.
AB  - Human placentation displays many similarities with tumourigenesis, including
      rapid cell division, migration and invasion, overlapping gene expression profiles
      and escape from immune detection. Recent data have identified promoter
      methylation in the Ras association factor and adenomatous polyposis coli tumour
      suppressor genes as part of this process. However, the extent of tumour
      associated methylation in the placenta remains unclear. Using whole genome
      methylation data as a starting point, we have examined this phenomenon in
      placental tissue. We found no evidence for methylation of the majority of common
      tumour suppressor genes in term placentas, but identified methylation in several
      genes previously described in some human tumours. Notably, promoter methylation
      of four independent negative regulators of Wnt signalling has now been identified
      in human placental tissue and purified trophoblasts. Methylation is present in
      baboon, but not in mouse placentas. This supports a role for elevated Wnt
      signalling in primate trophoblast invasiveness and placentation. Examination of
      invasive choriocarcinoma cell lines revealed altered methylation patterns
      consistent with a role of methylation change in gestational trophoblastic
      disease. This distinct pattern of tumour-associated methylation implicates a
      coordinated series of epigenetic silencing events, similar to those associated
      with some tumours, in the distinct features of normal human placental invasion
      and function.

PMID- 18708653
TI  - Evidence for transplacental and contact transmission of bluetongue virus in
      cattle.
AB  - This paper presents evidence that a field strain of bluetongue virus serotype 8
      (BTV-8) was transmitted transplacentally and that it was also spread by a direct
      contact route. Twenty pregnant heifers were imported from the Netherlands into
      Northern Ireland during the midge-free season. Tests before and after the animals
      were imported showed that eight of them had antibodies to bluetongue virus, but
      no viral RNA was detected in any of them by reverse transcriptase-PCR (RT-PCR).
      Two of the seropositive heifers gave birth to three calves that showed evidence
      of bluetongue virus infection (RT-PCR-positive), and one of the calves was
      viraemic. Two further viraemic animals (one newly calved Dutch heifer, and one
      milking cow originally from Scotland) were also found to have been infected with
      BTV-8 and evidence is presented that these two animals may have been infected by
      direct contact, possibly through the ingestion of placentas infected with BTV-8.

PMID- 18708654
TI  - Maintenance of anaesthesia in sheep with isoflurane, desflurane or sevoflurane.
AB  - Rapid recovery from anaesthesia is advantageous in small ruminants, to reduce the
      risk of regurgitation. Theoretically, the least soluble inhalation agents should
      result in the fastest recoveries, but using additional injectable agents may
      negate this advantage. This study compared three inhalation agents for the
      maintenance of anaesthesia in sheep. Eighteen ewes that were to undergo
      orthopaedic surgery were allocated to one of three groups. Each group was
      premedicated with xylazine (0.1 mg/kg intramuscularly), anaesthesia was induced
      using ketamine (2 mg/kg) and midazolam (0.03 mg/kg) intravenously and analgesia
      provided by buprenorphine (0.008 mg/kg intramuscularly). Anaesthesia was then
      maintained with either isoflurane, sevoflurane or desflurane. Cardiopulmonary
      parameters were monitored throughout. All three inhalation agents provided
      adequate stable anaesthesia and there was no significant difference between the
      groups in their cardiopulmonary parameters or their recovery times. The mead (sd)
      postanaesthetic times to first swallow, first chewing attempts and ability to
      maintain their head lifted for five minutes were, respectively, 3.95 (2.53), 6.37
      (3.68) and 32.8 (18.1) minutes for isoflurane, 3.62 (0.98), 7.66 (0.78) and 38.8
      (16.6) minutes for sevoflurane, and 4.37 (1.65), 6.95 (1.52) and 29.8 (11.5)
      minutes for desflurane. Two sheep had poor quality recoveries after the use of
      sevoflurane, but all the other sheep recovered uneventfully. All three inhalation
      agents were suitable for the maintenance of anaesthesia in sheep but, as used in
      this study, there were no differences between them in speed of recovery.

PMID- 18708655
TI  - Clinical signs and diagnosis of thiamine deficiency in juvenile goshawks
      (Accipiter gentilis).
AB  - Between 2002 and 2006, a large number of juvenile northern goshawks (Accipiter
      gentilis) with central nervous signs were examined. They were aged between 45 and
      55 days and had been fed on frozen and thawed day-old chicks. High-performance
      liquid chromatography showed that the birds had whole blood thiamine levels
      between 2.2 and 6.0 microg/l; the concentrations of other blood constituents were
      within their reference ranges. Treatment with thiamine hydrochloride rapidly
      resolved the clinical signs. Measurements of the concentration of thiamine in 22
      free-ranging and captive goshawks showed that they ranged from 45.1 to 200
      microg/l.

PMID- 18708656
TI  - Enteric mucosal antibodies to Escherichia coli O157:H7 in adult cattle.

PMID- 18708657
TI  - Nasal dermoid sinus cyst in a shih tzu.

PMID- 18708658
TI  - Confirmation by PCR of Coxiella burnetii infection in animals at a zoo in Lisbon,
      Portugal.

PMID- 18708659
TI  - Dentistry and the curriculum.

PMID- 18708660
TI  - Sequencing veterinary pathogens.

PMID- 18708661
TI  - Emergency euthanasia of poultry and gamebirds.

PMID- 18708662
TI  - Incomplete ossification of the humeral condyle in springer spaniels.

PMID- 18708664
TI  - Factors that contribute to the misidentification of tyrosine nitration by shotgun
      proteomics.
AB  - The high selectivity and throughput of tandem mass spectrometry allow for rapid
      identification and localization of various posttranslational protein
      modifications from complex mixtures by shotgun approaches. Although sequence
      database search algorithms provide necessary support to process the potentially
      enormous quantity of MS/MS spectra generated from large scale tandem mass
      spectrometry experiments, false positive identifications of peptide modifications
      may exist even after implementation of stringent identification criteria. In this
      report, we describe factors that lead to misinterpretation of MS/MS spectra as
      well as common chemical and experimental artifacts that generate false positives
      using the proteomics-based identification of tyrosine nitration as an example. In
      addition to the proposed manual validation criteria, the importance of peptide
      synthesis and subsequent MS/MS characterization for validation of peptide
      nitration demonstrated by several examples from earlier publications is also
      presented.

PMID- 18708665
TI  - Phosphomimetic mutations increase phospholamban oligomerization and alter the
      structure of its regulatory complex.
AB  - To investigate the effect of phosphorylation on the interactions of phospholamban
      (PLB) with itself and its regulatory target, SERCA, we measured FRET from CFP
      SERCA or CFP-PLB to YFP-PLB in live AAV-293 cells. Phosphorylation of PLB was
      mimicked by mutations S16E (PKA site) or S16E/T17E (PKA+CaMKII sites). FRET
      increased with protein concentration up to a maximum (FRET(max)) that was taken
      to represent the intrinsic FRET of the bound complex. The concentration
      dependence of FRET yielded dissociation constants (K(D)) for the PLB-PLB and PLB
      SERCA interactions. PLB-PLB FRET data suggest pseudo-phosphorylation of PLB
      increased oligomerization of PLB but did not alter PLB pentamer quaternary
      structure. PLB-SERCA FRET experiments showed an apparent decrease in binding of
      PLB to SERCA and an increase in the apparent PLB-SERCA binding cooperativity. It
      is likely that these changes are secondary effects of increased oligomerization
      of PLB; a change in the inherent affinity of monomeric PLB for SERCA was not
      detected. In addition, PLB-SERCA complex FRET(max) was reduced by phosphomimetic
      mutations, suggesting the conformation of the regulatory complex is significantly
      altered by PLB phosphorylation.

PMID- 18708666
TI  - Expression and functional characterisation of the putative SARS coronavirus non
      structural proteins X1-X5.
AB  - 1. We produced mammalian expression vectors encoding the SARS coronavirus (SARS
      CoV) accessory proteins with or without the fluorescence protein tag and cell
      lines with stable expression of these proteins. 2. The cellular localisation and
      function of the SARS-CoV accessory proteins was determined. 3. SARS 6 and SARS 8b
      proteins are localised to the endoplasmic reticulum and nucleus/cytoplasm,
      respectively, and both proteins stimulate host cell DNA synthesis.

PMID- 18708667
TI  - SARS coronavirus and apoptosis.
AB  - 1. The adenovirus-mediated overexpression of SARS coronavirus (SARS-CoV) spike
      protein (S) and its C-terminal domain (S2) induce apoptosis in Vero E6 cells. 2.
      Such apoptosis in Vero E6 cells is time- and dose-dependent. 3. The adenovirus
      mediated overexpression of SARS-CoV N-terminal domain (S1) and other structural
      proteins, including E,M and N protein, do not induce apoptosis.

PMID- 18708668
TI  - Molecular and genetic characterisation of the SARS coronavirus auxiliary protein
      X1 in Drosophila.
AB  - 1. We have generated monoclonal antibodies against the SARS coronavirus (SARS
      CoV) X1/3a protein (3a), which are suitable for western blotting,
      immunocytochemistry, and immunohistochemistry. 2. We have established and
      characterised an in-vivo 3a transgenic Drosophila model, and demonstrated its
      usefulness in studying SARS-CoV 3a gene function. 3. We validated our in-vivo
      findings on 3a gene function in mammalian Vero E6 cells. 4. Our findings raise
      the possibility of using ion channel blockers as a novel approach to suppress
      SARS-CoV-induced cell death.

PMID- 18708669
TI  - Risk-stratified seroprevalence of SARS coronavirus in children residing in a
      district with point-source outbreak compared to a low-risk area.
AB  - 1. SARS coronavirus has low transmissibility at the community level. 2.
      Subclinical SARS coronavirus infection is rare in children.

PMID- 18708670
TI  - Mechanisms of lymphocyte loss in SARS coronavirus infection.
AB  - 1. Human lymphocytes and monocytes are not permissive to productive SARS
      coronavirus (SARS-CoV) infection in vitro. 2. Challenge of lymphocytes and
      monocytes with infectious SARS-CoV, inactivated virions, and receptor-binding
      fragment of spike protein does not trigger apoptosis. 3. Direct
      infection/interaction between viruses and lymphocytes/monocytes is unlikely to be
      the cause of lymphopaenia in SARS patients. 4. Lymphopaenia in SARS patients is
      likely to result from indirect mechanisms secondary to the viral infection.

PMID- 18708671
TI  - Investigation of immunogenic T-cell epitopes in SARS virus nucleocapsid protein
      and their role in the prevention and treatment of SARS infection.
AB  - 1. A novel HLA-A2.1-specific SARS coronavirus (SARS-CoV) nucleocapsid (N) protein
      epitope (N220-N228 LALLLLDRL) able to activate cytotoxic T cells in vitro has
      been identified. 2. When used with a single-chain-trimer system, the SARS-CoV N
      protein epitope (N220-N228 LALLLLDRL) can stimulate a cytotoxic T-cell response
      against N-protein expressing cells in the HLA-A2.1K(b) transgenic mouse model.

PMID- 18708672
TI  - Role of polymorphisms of the inflammatory response genes and DC-SIGNR in genetic
      susceptibility to SARS and other infections.
AB  - 1. A genetic risk-association study involving more than 1200 subjects showed
      individuals homozygous for L-SIGN tandem repeats are less susceptible to SARS
      infection. 2. This was supported by in vitro binding studies that demonstrated
      homozygous L-SIGN, compared to heterozygous, had higher binding capacity for SARS
      coronavirus (SARS-CoV), with higher proteasome-dependent viral degradation. In
      contrast, homozygous L-SIGN demonstrated lower binding capacity for HIV1-gp120.3.
      Genetic-association studies for single nucleotide polymorphisms of the
      inflammatory response genes, namely TNF-alpha, INF-alpha, INF-beta, INF-gamma,
      IL1-alpha, IL1-beta, IL-4, IL-6 and iNOS, failed to show a significant
      association with SARS clinical outcomes or susceptibility.

PMID- 18708673
TI  - Helicases as antiviral drug targets.
AB  - 1. We have demonstrated for the first time that the helicase of a ribonucleic
      acid virus, the SARS coronavirus (SARS-CoV), is a valid target for drug
      development. 2. Using high throughput screen and chemical synthesis, several lead
      compounds targeting the SARS-CoV helicase have been identified. We have shown
      that these compounds can inhibit SARS-CoV helicase activity and viral growth in
      cell culture systems. These compounds can potentially be used to target other
      viruses.

PMID- 18708674
TI  - Studies of SARS virus vaccines.
AB  - 1. Intranasal vaccination using inactivated SARS coronavirus (SARS-CoV) vaccine
      with adjuvant can induce strong systemic (serum immunoglobulin [Ig] G) and
      respiratory tract local (tracheal-lung wash fluid IgA) antibody responses with
      neutralising activity. 2. RBD-Fc (protein-based vaccine) is able to induce
      effective neutralising antibodies able to provide protection from SARS-CoV
      infection in animal models. 3. A single dose of RBD-rAAV vaccination can induce
      adequate neutralising antibody against SARS-CoV infection. 4. Additional doses of
      vaccine increased the production of neutralising antibody 5-fold compared with a
      single dose. 5. RBD-rAAV vaccination provoked a prolonged antibody response with
      continually increasing levels of neutralising activity. 6. Intranasal vaccination
      with RBD-rAAV induced local IgA and systemic IgG neutralising antibodies and
      specific T-cell responses, able to protect against SARS-CoV infection in animal
      models. 7. When compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV
      prime/RBD-peptide boost induced similar levels of Th1 and neutralising antibody
      responses that protected vaccinated mice from subsequent SARS-CoV challenges,but
      stronger Th2 and CTL responses. 8. Overall, our findings suggest that the
      inactivated vaccine, RBD-Fc and RBD-rAAV, can be further developed into effective
      and safe vaccines against SARS and that intranasal vaccination may be the
      preferred route of administration.

PMID- 18708675
TI  - An evaluation of SARS and droplet infection control practices in acute and
      rehabilitation hospitals in Hong Kong.
AB  - 1. This study has demonstrated that great efforts have been made by the Hospital
      Authority and the studied hospital cluster to contain and prevent infection, and
      that high levels of vigilance have been enforced in anticipation of future
      outbreaks of SARS and other droplet infections. 2. Most health care workers and
      support workers have good hospital infection control and isolation precaution
      knowledge levels. 3. Compliance with infection control guidelines is satisfactory
      and has increased compared with previous studies. 4. Most participants had
      positive perceptions of the guidelines and found the training programmes useful.
      5. This study has identified several structures and infection control practice
      areas that need strengthening, including improving the clarity of some guidelines
      and minimising barriers to their implementation.

PMID- 18708676
TI  - Effectiveness of clinical ultrasound parameters on changing intramuscular
      temperature.
AB  - CONTEXT: Researchers have recommended certain ultrasound treatment parameters for
      deep heating; however, we observed different parameters in the clinical setting.
      OBJECTIVE: To compare the treatment effect of using observed clinical parameters
      (OCP) from 8 clinicians to the treatment effect of using the recommended
      parameters (RP) sited in research. DESIGN: 2 x 2 repeated measures design.
      SETTING: Sports injury research laboratory. PARTICIPANTS: Ten healthy volunteers.
      INTERVENTIONS: Two 1 MHz treatment, 1 RP treatment (1.5 W/cm2, 10-min, area-2 to
      3 x ERA), and 1 OCP treatment (1.3 W/cm2, 8-min, area 3.9 X ERA). MAIN OUTCOME
      MEASURE: Tricep surae temperature 3 cm below superficial tissue. RESULTS: The RP
      treatment increase temperature from 36.4 +/- 1.0 to 40.3+/- 2.0 degrees C, which
      was a greater change than the OCP (36.5 +/- 1.2 to 38.2 +/- 1.6 degrees C).
      CONCLUSIONS: The OCP treatment resulted in a lower heating affect than the RP.
      Small change in treatment area, intensity, and duration can have a large effect
      on temperature change.

PMID- 18708677
TI  - Impact attenuation and variability during running in females: a lifespan
      investigation.
AB  - CONTEXT: Impact is known to cause injury during running, while variability is
      thought to promote healthy performance. OBJECTIVE: Quantify contributions of the
      lower extremity and back and the variability of impact generation among (1)
      prepubescent girls (Grp 1), (2) normally menstruating women (Grp 2), and (3)
      postmenopausal women (Grp 3) to address possible lifespan changes during running.
      DESIGN: A mixed model experiment. SETTING: Biomechanics Laboratory. PARTICIPANTS:
      31 healthy females owing membership to Grp1, Grp 2, or Grp 3. INTERVENTION:
      Participants ran on a treadmill at their preferred speed (45 s) and at a speed
      10% faster (45 s) while instrumented with uniaxial accelerometers. MAIN OUTCOME
      MEASURES: Lower extremity attenuation, back attenuation and variability of peak
      impact acceleration values. RESULTS: Lower extremity attenuation and variability
      were greatest for Grp 1 while impact variability was least for Grp 2. CONCLUSION:
      Lifespan phases appear to affect impact attenuation strategies and variability of
      impact during running for females.

PMID- 18708678
TI  - Hip abductor weakness and lower extremity kinematics during running.
AB  - OBJECTIVE: To determine if females with hip abductor weakness are more likely to
      demonstrate greater knee abduction during the stance phase of running than a
      strong hip abductor group. STUDY DESIGN: Observational prospective study design.
      SETTING: University biomechanics laboratory. PARTICIPANTS: 15 females with weak
      hip abductors and 15 females with strong hip abductors. MAIN OUTCOME MEASURES:
      Group differences in lower extremity kinematics were analyzed using repeated
      measures ANOVA with one between factor of group and one within factor of position
      with a significance value of P < .05. RESULTS: The subjects with weak hip
      abductors demonstrated greater knee abduction during the stance phase of
      treadmill running than the strong group (P < .05). No other significant
      differences were found in the sagittal or frontal plane measurements of the hip,
      knee, or pelvis. CONCLUSIONS: Hip abductor weakness may influence knee abduction
      during the stance phase of running.

PMID- 18708679
TI  - The effects of eversion fatigue on frontal plane joint position sense in the
      ankle.
AB  - CONTEXT: There is limited information on fatigue of the evertors on frontal plane
      joint position sense (JPS). OBJECTIVE: To examine the effects of isokinetic
      concentric-eccentric fatigue of the evertors on frontal plane JPS of the ankle.
      DESIGN: A2 x 4 factorial design. SETTING: Research Laboratory. PATIENTS OR OTHER
      PARTICIPANTS: 40 male and female healthy subjects. INTERVENTIONS: JPS was tested
      at 10 degrees and 20 degrees of inversion and 5 degrees and 10 degrees of
      eversion in a nonfatigued/fatigued condition. After fatigue of evertors was
      determined on an isokinetic device, post fatigue testing of JPS occurred. MAIN
      OUTCOME MEASURES: JPS absolute error (AE) for inversion and eversion. RESULTS:
      Main effect for condition and angle were significant with pre/post fatigue. There
      were overestimation of angles postfatigue with AE greater at 20 degrees of
      inversion (P = .003), followed by 10 degrees of inversion (P < .001), 10 degrees
      of eversion (P = .005), and 5 degrees of eversion (P = .005). CONCLUSION: When
      the ankle evertors were fatigued, the AE for JPS was significantly higher at all
      test angles.

PMID- 18708680
TI  - The transtheoretical model: an exploratory look at its applicability to injury
      rehabilitation.
AB  - CONTEXT: The transtheoretical model has been widely used in the investigation of
      how people adapt to new behaviors; however, the literature appears to be lacking
      documentation of any assessment/s administered to injured athletes to determine
      their readiness for rehabilitation, which depending on the severity of the
      injury, could possibly represent a behavior change for that individual.
      OBJECTIVE: To validate the application of the transtheoretical model to injury
      rehabilitation and assess the impact of stages of change on athletes' adherence
      and compliance rates. DESIGN: Descriptive correlational. SETTING: Large Mid
      Atlantic Division I institution. PARTICIPANTS: Seventy injured athletes. MAIN
      OUTCOME MEASURES: Readiness was assessed using the Transtheoretical Model.
      Adherence was assessed using the percentage of rehabilitation attendance and
      compliance was assessed using the Sport Injury Rehabilitation Scale. RESULTS:
      Participants who were advanced in their stages of change generally reported an
      increase in self efficacy, utilization of pros versus cons, and the use of
      behavioral processes instead of experiential processes of change. No significant
      relationships were found between stages of change and athletes' adherence and
      compliance. CONCLUSION: Although no statistical significance was found between
      stages of change and adherence and compliance the results did validate the
      application of the transtheoretical model to injury rehabilitation.

PMID- 18708681
TI  - Contribution of the multifidus muscle for control of upright posture in subjects
      with spina bifida occulta.
AB  - CONTEXT: The multifidus muscle plays a role in controlling lumbosacral position
      and postural sway. One of its attachment sites is the exact site of spina bifida
      occulta (SBO). OBJECTIVE: To investigate the role of the muscle for postural
      control in SBO. DESIGN: Cross-sectional cohort. PARTICIPANTS: Eighty subjects
      with SBO (38 in minor; 42 in major) and controls. INTERVENTIONS: N/A. MAIN
      OUTCOME MEASURES: Subjects stood upright on a platform at 0 degrees and on an
      inclined surface (10 degrees and 20 degrees) with feet in
      plantarflexion/dorsiflexion, together with eyes open and closed. The platform
      system measured posture to obtain sway area and sway mean for statistics.
      RESULTS: Upon sway area/mean, the group differences of major/minor SBO vs.
      control were all significant. Sway means of minor SBO were lower than those of
      major SBO at corresponding inclined degrees. CONCLUSIONS: Subjects with SBO
      demonstrated increased sway as compared to controls.

PMID- 18708682
TI  - Tibiofemoral joint kinetics during squatting with increasing external load.
AB  - CONTEXT: There is limited information about the effects of increasing load while
      squatting. OBJECTIVE: To quantify tibiofemoral joint kinetics during squatting
      with variable loads. SETTING: Research laboratory. PARTICIPANTS: 20 male
      students. INTERVENTION: Tibiofemoral joint kinetics and electromyographic (EMG)
      activity of four involved muscles were determined by recording the half squat
      with variable external loads. MAIN OUTCOME MEASURES: Tibiofemoral joint force and
      external moment components and EMG activity of four involved muscles. RESULTS:
      Throughout the exercise, a posterior direction for the antero-posterior shear
      force and a net extension for the external moment were observed. They increased
      with knee flexion reaching peak force of 29% of the subject body weight (BW) and
      moment of 88Nm (without external load). All force and moment components and
      muscle activities increased as the external load increased. CONCLUSION: These
      findings suggest that half squat may be safe to use for quadriceps strengthening
      with very low potential loading on the anterior cruciate ligament (ACL). Our data
      can help clinicians choose the appropriate external load.

PMID- 18708683
TI  - The effectiveness of balance training programs on reducing the incidence of ankle
      sprains in adolescent athletes.
AB  - Ankle sprains are one of the most common sport-related injuries treated by
      rehabilitation professionals. These injuries often result in lost participation
      and can lead to subsequent injury episodes. Therefore, it is important to
      determine appropriate means of preventing these injuries. There has recently been
      an increase in the popularity of balance training programs for the prevention of
      knee anterior cruciate ligament (ACL) injury, with some thought that starting
      these programs in younger athletes may be most beneficial. However, there is the
      potential that these types of training programs may also be beneficial for
      decreasing the risk of other lower extremity injuries, including ankle sprains in
      the adolescent athlete.

PMID- 18708684
TI  - Neural gliding techniques for the treatment of carpal tunnel syndrome: a
      systematic review.
AB  - CONTEXT: There are discrepancies regarding the efficacy of neural gliding
      exercises for the management of carpal tunnel syndrome (CTS). OBJECTIVE: To
      conduct a systematic review assessing the efficacy of neural gliding in
      comparison to alternative nonsurgical treatment for the management of CTS.
      EVIDENCE ACQUISITION: A computerized search was performed in April 2008. Criteria
      for inclusion required that studies (1) were written in English, (2) examined the
      efficacy of neural gliding techniques for treatment of CTS, and (3) included at
      least one of the selected patient-oriented outcomes. Effect sizes, relative risk,
      and 95% confidence intervals were calculated to compare neural gliding to
      alternative treatment. EVIDENCE SYNTHESIS: Six studies met inclusion criteria.
      For all variables, none were consistently favorable toward neural gliding over
      alternative treatment. However, comparisons across studies revealed a possible
      trend toward improved outcomes with the use neural gliding. CONCLUSIONS: The
      efficacy of neural gliding is not clear. More research is necessary to determine
      the population that may respond optimally to this treatment.

PMID- 18708685
TI  - The effect of caffeine as an ergogenic aid in anaerobic exercise.
AB  - The study examined caffeine (5 mg/kg body weight) vs. placebo during anaerobic
      exercise. Eighteen male athletes (24.1+/-5.8 yr; BMI 26.4+/-2.2 kg/m2) completed
      a leg press, chest press, and Wingate test. During the caffeine trial, more total
      weight was lifted with the chest press, and a greater peak power was obtained
      during the Wingate test. No differences were observed between treatments for the
      leg press and average power, minimum power, and power drop (Wingate test). There
      was a significant treatment main effect found for postexercise glucose and
      insulin concentrations; higher concentrations were found in the caffeine trial. A
      significant interaction effect (treatment and time) was found for cortisol and
      glucose concentrations; both increased with caffeine and decreased with placebo.
      Postexercise systolic blood pressure was significantly higher during the caffeine
      trial. No differences were found between treatments for serum free-fatty-acid
      concentrations, plasma lactate concentrations, serum cortisol concentrations,
      heart rate, and rating of perceived exertion. Thus, a moderate dose of caffeine
      resulted in more total weight lifted for the chest press and a greater peak power
      attained during the Wingate test in competitive athletes.

PMID- 18708686
TI  - Influence of carbohydrate-protein beverage on cycling endurance and indices of
      muscle disruption.
AB  - Carbohydrate-protein (CHO+Pro) beverages reportedly improve endurance and indices
      of muscle disruption, but it is unclear whether these effects are related to
      total energy intake or specific effects of protein. PURPOSE: The authors examined
      effects of CHO+Pro on time to exhaustion and markers of muscle disruption
      compared with placebo (PLA) and carbohydrate beverages matched for carbohydrate
      (CHO) and total calories (CHO+CHO). METHODS: Eleven male cyclists completed 4
      rides to exhaustion at 75% VO2peak. Participants consumed 250 ml of PLA, CHO
      (7.75%), CHO+CHO (9.69%), or CHO+Pro (7.75%/1.94%) every 15 min until fatigue, in
      a double-blind design. RESULTS: Time to exhaustion was significantly longer
      (p<.05) in CHO+Pro (126.2+/-25.4 min) and CHO+CHO (121.3+/-36.8) than PLA
      (107.1+/-30.3). CHO (117.5+/-24.2) and PLA were not significantly different.
      Similarly, CHO+Pro was not significantly different from CHO and CHO+CHO.
      Postexercise plasma creatine kinase was lower after CHO+Pro (197.2+/-149.2 IU/L)
      than PLA (407.4+/-391.3), CHO (373.2+/-416.6), and CHO+CHO (412.3+/-410.2).
      Postexercise serum myoglobin was lower in CHO+Pro (47.0+/-27.4 ng/mL) than all
      other treatments (168.8+/-217.3, 82.6+/-71.3, and 72.0+/-75.8). Postexercise leg
      extensions at 70% 1RM were significantly greater 24 hr after CHO+Pro (11.3+/-4.1)
      than PLA (8.8+/-3.7), CHO (9.7+/-4.3), and CHO+CHO (9.5+/-3.6). CONCLUSION: These
      findings suggest that at least some of the reported improvements in endurance
      with CHO+Pro beverages might be related to caloric differences between
      treatments. Postexercise improvements in markers of muscle disruption with
      CHO+Pro ingestion appear to be independent of carbohydrate and caloric content
      and were elicited with beverages consumed only during exercise.

PMID- 18708687
TI  - N-acetylcysteine supplementation and oxidative damage and inflammatory response
      after eccentric exercise.
AB  - The objective of the study was to verify the effect of N-acetylcysteine (NAC)
      supplementation on parameters of oxidative damage and inflammatory response after
      high-intensity eccentric exercise (EE). 29 participants with a mean age of 21.3+/
      4 yr, weight of 74.5+/-7.7 kg, and height of 177.2+/-6.9 cm were selected and
      divided randomly into 3 groups: placebo (21 days; n=8), NAC (21 days; n=9), and
      NAC plus placebo (14 days; n=8). Four participants withdrew from the study for
      personal reasons. 14 days after starting supplementation, the participants
      performed EE: 3 sets until exhaustion (elbow flexion and extension on the Scott
      bench, 80% 1RM). Blood samples were collected before and on the 2nd, 4th, and 7th
      day after EE. Muscle soreness (MS), lipoperoxidation, protein carbonylation,
      tumor-necrosis factor- (TNF-), and interleukin 10 (IL-10) were determined.
      Results showed a significant increase in MS in all the groups on the 2nd day
      after EE and a decrease in the following days. A significant increase was
      observed in malondialdehyde and carbonyl levels on the 4th and 7th days after EE
      in all groups. TNF- increased significantly on the 2nd day after eccentric
      exercise and decreased in the following days irrespective of NAC supplementation;
      concentration of IL-10 increased significantly on the 4th day in all groups. Only
      the supplemented groups maintained high levels of IL-10 on the 7th day after EE.
      The results suggest that treatment with NAC represents an important factor in the
      defense against muscle soreness and has different effects on oxidative damage and
      pro- and anti-inflammatory cytokines.

PMID- 18708688
TI  - Effect of creatine supplementation and resistance-exercise training on muscle
      insulin-like growth factor in young adults.
AB  - The purpose of this study was to compare changes in muscle insulin-like growth
      factor-I (IGF-I) content resulting from resistance-exercise training (RET) and
      creatine supplementation (CR). Male (n=24) and female (n=18) participants with
      minimal resistance-exercise-training experience (=1 year) who were participating
      in at least 30 min of structured physical activity (i.e., walking, jogging,
      cycling) 3-5 x/wk volunteered for the study. Participants were randomly assigned
      in blocks (gender) to supplement with creatine (CR: 0.25 g/kg lean-tissue mass
      for 7 days; 0.06 g/kg lean-tissue mass for 49 days; n=22, 12 males, 10 female) or
      isocaloric placebo (PL: n=20, 12 male, 8 female) and engage in a whole-body RET
      program for 8 wk. Eighteen participants were classified as vegetarian (lacto-ovo
      or vegan; CR: 5 male, 5 female; PL: 3 male, 5 female). Muscle biopsies (vastus
      lateralis) were taken before and after the intervention and analyzed for IGF-I
      using standard immunohistochemical procedures. Stained muscle cross-sections were
      examined microscopically and IGF-I content quantified using image-analysis
      software. Results showed that RET increased intramuscular IGF-I content by 67%,
      with greater accumulation from CR (+78%) than PL (+54%; p=.06). There were no
      differences in IGF-I between vegetarians and nonvegetarians. These findings
      indicate that creatine supplementation during resistance-exercise training
      increases intramuscular IGF-I concentration in healthy men and women, independent
      of habitual dietary routine.

PMID- 18708689
TI  - Chicken breast attenuates high-intensity-exercise-induced decrease in rat
      sarcoplasmic reticulum Ca2+ handling.
AB  - This study was conducted to determine whether dietary chicken-breast extract
      (CBEX), a rich source of histidine-containing dipeptides, could modify exercise
      induced changes in sarcoplasmic reticulum (SR) function. After 5 weeks of dietary
      CBEX, SR Ca2+-handling ability was examined in the vastus lateralis muscles of
      rats subjected to high-intensity running for 2.5 min. Dietary CBEX caused an
      approximately 15% and 45% increase (p<.01) in muscle carnosine and anserine
      concentrations, respectively. In resting muscles, depressions in SR Ca2+-ATPase
      activity were evoked by dietary CBEX without concomitant changes in SR Ca2+
      uptake and release rates. The data confirm that high-intensity exercise depresses
      SR Ca2+ handling. In spite of the same run time, SR Ca2+ handling was reduced to
      a lesser degree in muscles of CBEX-containing-chow-fed rats than in standard-chow
      fed rats (p<.05). These results suggest that dietary CBEX might attenuate
      deteriorations in SR Ca2+-handling ability that occur with high-intensity
      exercise.

PMID- 18708690
TI  - A food pyramid for Swiss athletes. Interview by Louise M. Burke.

PMID- 18708691
TI  - Quantitative analysis of urinary glycerol levels for doping control purposes
      using gas chromatography-mass spectrometry.
AB  - The administration of glycerol to endurance athletes results in an increased
      fluid retention and improved performance, particularly under hot and humid
      conditions. Consequently, glycerol is considered relevant for sports drug testing
      and methods for its detection in urine specimens are required. A major issue in
      this regard is the natural occurrence of trace amounts of glycerol in human
      urine, which necessitates a quantitative analysis and the determination of normal
      urinary glycerol levels under various sporting conditions. A quantitative method
      was established using a gas chromatography/isotope-dilution mass spectrometry
      based approach that was validated with regard to lower limit of detection (0.3
      microg mL(-1)), lower limit of quantification (0.9 microg mL(-1)), specificity,
      linearity (1.0-98.0 microg mL(-1)), intraday and interday precision (<20% at 2.4,
      24.1 and 48.2 microg mL(-1)) as well as accuracy (92-110%). Sample aliquots of 20
      microL were enriched with five-fold deuterated glycerol, dried and derivatised
      using N-methyl-trimethylsilyltrifluoroacetamide (MSTFA) before analysis. The
      established method was applied to a total of 1039 doping control samples covering
      various sport disciplines (349 endurance samples, 286 strength sport samples, 325
      game sport samples and 79 other samples) in- and out-of-competition, which
      provided quantitative information about the glycerol content commonly observed in
      elite athletes' urine samples. About 85% of all specimens yielded glycerol
      concentrations < 20.0 microg mL(-1) and few reached values up to 132.6 microg mL(
      1). One further sample, however, was found to contain 2690 microg mL(-1), which
      might indicate the misuse of glycerol, but no threshold for urinary glycerol
      concentrations has been established yet due to the lack of substantial data.
      Based on the results obtained from the studied reference population, a threshold
      for glycerol levels in urine set at 200 microg mL(-1) is suggested, which
      provides a tool to doping control laboratories to test for the misuse of this
      agent in elite and amateur sport.

PMID- 18708692
TI  - Identification and quantification of the osmodiuretic mannitol in urine for
      sports drug testing using gas chromatography-mass spectrometry.
AB  - The osmodiuretic mannitol can be potentially misused in sports, owing to its
      urine diluting effect and the possibility to decrease bodyweight. To reveal a
      doping offence, resulting urinary mannitol concentrations after a prohibited
      intravenous application and a permitted oral intake have to be differentiated.
      Therefore, a reliable gas chromatography-mass spectrometry (GC-MS) method was
      established based on peracetyl derivatives of the analytes. All possible hexitols
      (allitol, galactitol, iditol, altritols, sorbitol and mannitol) that can occur in
      human urine were separated and identified on a phenyl-methylpolysiloxane column
      (HP-5MS) within 10.75 min, and the method demonstrated its capability for
      quantification purposes. The lower limit of detection and lower limit of
      quantification were estimated at 0.9 microg mL(-1) and 2.4 microg mL(-1),
      respectively, and the assay was validated for mannitol and sorbitol regarding the
      parameters specificity, linearity, intra- (<10%) and inter-day precision (<15%)
      and accuracy (92-102%). To investigate urinary mannitol concentrations after oral
      intake the method was applied to an excretion study, providing a mean urinary
      excretion of mannitol of 19.5%. Comparison of theoretically expected urinary
      levels after a common therapeutic dose of mannitol and preliminary results on
      physiological urinary mannitol levels were promising, regarding a threshold level
      for mannitol that can be utilised for doping control purposes.

PMID- 18708693
TI  - Determination of selected stimulants in urine for sports drug analysis by solid
      phase extraction via cation exchange and means of liquid chromatography-tandem
      mass spectrometry.
AB  - Stimulatory substances applied during competition possess a reasonable potential
      as performance enhancing agents and their misuse in elite sport has been
      frequently reported during the last few decades. An analytical method for the
      qualitative determination of selected stimulants containing a primary or
      secondary amine moiety in human urine for doping control purposes was developed.
      A rapid and highly specific procedure based on a sample preparation using weak
      cation exchange solid phase extraction (SPE-XCW) followed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) with a C6-Phenyl analytical
      column allowed the unambiguous identification of the target analytes down to low
      ng mL(-1) concentration levels. Validation provided recovery rates of better than
      75%, precisions of less than 20% and a linear approximation in the required
      working range (10-750 ng mL(-1)) were obtained for 19 different target compounds.
      This method provides a rugged and highly specific alternative to the established
      method utilising gas or liquid chromatography after liquid-liquid extraction.

PMID- 18708694
TI  - Doping control analysis of methoxyphenamine using liquid chromatography-tandem
      mass spectrometry.
AB  - Methoxyphenamine (o-methoxy-N,alpha-dimethylphenethylamine, Orthoxine) used in
      earlier times as a bronchodilator is prohibited in sports according to the
      regulations of the World Anti-Doping Agency (WADA). The drug and several of its
      metabolites are commonly analysed in doping control screening assays using gas
      chromatography-mass spectrometry requiring extraction from urine specimens. A
      complementary method employing liquid chromatography-atmospheric pressure
      chemical ionisation-tandem mass spectrometry and direct injection of urine
      aliquots was developed, which provided a fast and sensitive alternative to
      confirm the presence of the prohibited compound and degradation products in
      sports drug testing samples. In particular, the chromatographic separation of the
      active drug from isomeric compounds such as the designer drug p
      methoxymetamphetamine (PMMA) was of particular interest to unambiguously identify
      the applied substance and was accomplished using a C6-phenyl reverse-phase column
      with isocratic elution. The established procedure was validated for
      methoxyphenamine with regard to specificity, limit of detection (0.7 ng mL(-1)),
      intraday- and interday precision (2.5-5.8% and 10.8-16.2%, respectively) and its
      applicability was demonstrated with an authentic doping control sample which
      tested positive for the prohibited compound early in 2008.

PMID- 18708695
TI  - Screening for two selective androgen receptor modulators using gas chromatography
      mass spectrometry in doping control analysis.
AB  - Selective androgen receptor modulators (SARMs) have become a major field of
      clinical research enabling the tissue-selective stimulation of androgen
      receptors. The treatment of debilitating diseases, osteoporosis and frailty are
      primary goals and promising results have been obtained from clinical trials.
      However, the potential for misuse of SARMs in sport is great and drug testing
      methods based on liquid chromatography were established for different classes
      including arylpropionamide-, 2-quinolinone- and bicyclic hydantoin-derived
      compounds. As gas chromatography and mass spectrometry (GC-MS) are still
      important analytical tools in sports drug testing, a method to determine 2
      quinolinone- and bicyclic hydantoin-derived SARMs established. Spiked urine
      samples were subjected to routine doping control protocols including enzymatic
      hydrolysis, liquid-liquid extraction, concentration and derivatisation to
      trimethylsilylated analogues followed by GC-MS analysis. The method was validated
      for the items specificity, lower limit of detection (0.2-10 ng mL(-1)), recovery
      (83-85%), intraday and interday precision (9-15% and 13-18%, respectively), which
      demonstrates the suitability of conventional GC-MS systems to determine
      representatives of an emerging class of compounds in doping control specimens.

PMID- 18708696
TI  - Use of an electrochemically synthesised metabolite of a selective androgen
      receptor modulator for mass spectrometry-based sports drug testing.
AB  - The elucidation of the metabolism of new therapeutics is a major task for
      pharmaceutical companies and of great interest for drug testing laboratories. The
      latter in particular need to determine the presence or absence of drugs or their
      metabolic products in urine to test for a misuse of these compounds. Commonly, in
      vitro or animal models are used to mimic the human metabolism and produce
      potential targets in amounts allowing for method development. An alternative
      route based on electrochemical reactions of drugs was reported to allow for the
      generation of selected metabolites. The utility of this approach for doping
      control purposes was demonstrated with a novel class of anabolic agents termed
      selective androgen receptor modulators (SARMs). An arylpropionamide- derived drug
      candidate was subjected to electrochemical "metabolism" and a major phase-I-
      metabolite, resulting from the elimination of a substituted phenol residue as
      identified in in vitro experiments, was generated and characterised using liquid
      chromatography/nuclear magnetic resonance spectroscopy and high resolution/high
      accuracy mass spectrometry. The metabolite was included in routine doping control
      procedures based on liquid chromatography/tandem mass spectrometry and has served
      as a reference compound for 5000 doping control specimens.

PMID- 18708697
TI  - A mass spectrometric approach for the study of the metabolism of clomiphene,
      tamoxifen and toremifene by liquid chromatography time-of-flight spectroscopy.
AB  - In this paper, we discuss the capabilities of liquid chromatography coupled to
      mass spectrometry with a time-of flight system with accurate mass measurement for
      the detection and characterisation of drug metabolites in biological samples for
      anti-doping purpose. Urinary excretion samples of three selective oestrogen
      receptor modulators (SERMs) with a common triphenylethylene structure:
      clomiphene, toremifene, and tamoxifen, obtained after oral administration of a
      single dose of each drug, were analysed using a time-of-flight system, after
      automatic tuning and calibration of the equipment, in positive full scan mode
      using an electrospray ionisation source. Following this approach we detected most
      of all significant metabolites reported by others and postulated new metabolites,
      especially for toremifene, have been characterised: N-demethyl-3-hydroxy-4
      methoxy-toremifene and 3- hydroxy-4-methoxy-toremifene; in addtiona to this, in
      the urinary excretion samples of toremifene some metabolites, without the
      characteristic chlorine isotope pattern, discarded in previous studies, that are
      also metabolites of tamoxifen, were identified. The lack of certified reference
      materials does not allow an accurate determination of the limit of detection
      (LODs) of all metabolites; however an estimation taking into account the response
      factor of similar compounds allows to estimate that all metabolites are clearly
      detectable in a range of concentration comprised between 10 ng mL(-1) and 30 ng
      mL(-1).

PMID- 18708698
TI  - Screening of in vitro synthesised metabolites of 4,9,11-trien-3-one steroids by
      liquid chromatography mass spectrometry.
AB  - The aim of the work was to develop a flexible in vitro synthesis procedure, which
      can be applied in order to study and predict the metabolic patterns of new
      derivatives of anabolic androgenic steroids (AAS) with respect to most prominent
      target compounds for doping control purposes. Microsomal and S9 fraction of human
      liver preparations were used as a source of metabolising enzymes and the co
      substrates of the synthesis mixture were selected to favour phase-I metabolic
      reactions and glucuronidation as phase-II conjugation reactions. Model compounds
      within the study were 4,9,11-trien-3-one steroids, structural derivatives of
      gestrinone and trenbolone, which both are included in the list of prohibited
      compounds in sports by the World Anti-Doping Agency (WADA). The correlation
      between in vitro metabolism of human microsomes and in vivo excretion studies in
      human was compared with gestrinone and subsequently, the applicability of the in
      vitro model for prediction of AAS metabolic pathways for new doping agents was
      evaluated. All the AAS examined within this study were successfully metabolised
      using the developed in vitro model, hydroxylation, reduction and glucuronide
      conjugation being the most prominent reaction pathways. Hydroxylated and
      glucuronide-conjugated metabolites of in vivo experiment with gestrinone were the
      same metabolites formed in the enzyme-driven process, thus showing good in vitro
      in vivo correlation. Liquid chromatographic-mass spectrometric and tandem mass
      spectrometric methods were developed, relying on the positive polarity of
      electrospray ionisation, which also allowed the direct detection of intact
      glucuronide-conjugated AAS metabolites. Due to charge delocalisation and high
      proton affinity, the developed method was proven effective in the analysis of AAS
      metabolites bearing extensive conjugated double bond systems in their structures.

PMID- 18708699
TI  - High-throughput and sensitive screening by ultra-performance liquid
      chromatography tandem mass spectrometry of diuretics and other doping agents.
AB  - The reliability of ultra-performance liquid chromatography coupled to tandem mass
      spectrometry (UPLC- MS/MS) for high throughput screening in anti-doping control
      has been tested. A method to screen for the presence of diuretics and other
      doping agents in urine has been optimised and validated. The extraction procedure
      consisted of an alkaline extraction (pH 9.5) with ethyl acetate and salting-out
      effect (sodium chloride). The extracts were analysed by UPLC-MS/MS. Analysis of
      34 forbidden drugs and metabolites was achieved in a total run time of 5 min,
      using a C18 column (100 mm x 2.1 mm i.d., 1.7 microm particle size) and a mobile
      phase containing deionised water and acetonitrile with formic acid, with gradient
      elution at a flow-rate of 0.6 mL min(-1). Identification of the compounds was
      performed by multiple reaction monitoring, using electrospray ionisation in
      positive- or negative-ion mode. Precursor and product ions were studied for each
      compound and cone voltage and collision energy were optimised. Due to the
      different chemical structure of the compounds under study, extraction recoveries
      varied from less than 10% to 100% depending on the analyte. The limits of
      detection ranged from 50 ng mL(-1) to 200 ng mL(-1), and all the compounds comply
      with the requirements of quality established by the World Anti-doping Agency.
      Intra-assay precision was evaluated at two concentrations for each compound and,
      in most cases, a relative standard deviation of the signal ratio lower than 20%
      was obtained. The method has demonstrated to be reliable when analysing routine
      samples and the short analysis time resulting from a simple sample preparation
      and a rapid instrumental analysis allow a fast turn-around time and makes it of
      great interest for routine anti-doping control purposes.

PMID- 18708700
TI  - Possible indirect detection of rHuEPO administration in human urine by high
      performance liquid chromatography tandem mass spectrometry.
AB  - The present study is based on the assumption that changes in an ADMA-DDAH-NOS
      (ADMA-asymmetrical dimethylarginine; DDAH-dimethyl-arginine
      dimethylaminohydrolase; NOS-nitric oxide synthase) system could be employed as
      indirect markers for recombinant human erythropoietin (rHuEPO) administration in
      doping control. We assessed a predictive value of four proposed new markers for
      rHuEPO abuse. Preliminary data showed that concentrations of ADMA, symmetrical
      dimethylarginine (SDMA), citrulline and arginine in human urine were increased
      after administration of a single intravenous erythropoietin injection (2000 U
      day(-1), Epocrine, St-Petersburg, Russia). The study of variations of ADMA, SDMA,
      arginine and citrulline levels before and after rHuEPO administration was
      performed with two healthy male volunteers. Urine samples were collected before
      rHuEPO administration and urinary concentrations of ADMA and SDMA were determined
      at 10.0-40 microg mL(-1) and of arginine and citrulline at 0.5-10 microg mL(-1).
      A single dose injection of rHuEPO caused an increase in ADMA, SDMA, arginine and
      citrulline concentrations up to 40-270 microg mL(-1), 40-240 microg mL(-1), 10-60
      microg mL(-1) and 12-140 microg mL(-1), respectively. These preliminary results
      indicated that an indirect approach could be used as a pre-screening of urine
      samples in order to decrease the number of samples with a low probability of
      rHuEPO abuse and, thus, save costs and human workload.

PMID- 18708701
TI  - Permeability testing of biomaterial membranes.
AB  - The permeability characteristics of biomaterials are critical parameters for a
      variety of implants. To analyse the permeability of membranes made from
      crosslinked ultrathin gelatin membranes and the transmigration of cells across
      the membranes, we combined three technical approaches: (1) a two-chamber-based
      permeability assay, (2) cell culturing with cytochemical analysis and (3)
      biochemical enzyme electrophoresis (zymography). Based on the diffusion of a
      coloured marker molecule in conjunction with photometric quantification,
      permeability data for a gelatin membrane were determined in the presence or
      absence of gelatin degrading fibroblasts. Cytochemical evaluation after
      cryosectioning of the membranes was used to ascertain whether fibroblasts had
      infiltrated the membrane inside. Zymography was used to investigate the potential
      release of proteases from fibroblasts, which are known to degrade collagen
      derivatives such as gelatin. Our data show that the diffusion equilibrium of a
      low molecular weight dye across the selected gelatin membrane is approached after
      about 6-8 h. Fibroblasts increase the permeability due to cavity formation in the
      membrane inside without penetrating the membrane for an extended time period (>21
      days in vitro). Zymography indicates that cavity formation is most likely due to
      the secretion of matrix metalloproteinases. In summary, the combination of the
      depicted methods promises to facilitate a more rational development of
      biomaterials, because it provides a rapid means of determining permeability
      characteristics and bridges the gap between descriptive methodology and the
      mechanistic understanding of permeability alterations due to biological
      degradation.

PMID- 18708702
TI  - Deciphering cellular morphology and biocompatibility using polymer microarrays.
AB  - A quantitative and qualitative analysis of cellular adhesion, morphology and
      viability is essential in understanding and designing biomaterials such as those
      involved in implant surfaces or as tissue-engineering scaffolds. As a means to
      simultaneously perform these studies in a high-throughput (HT) manner, we report
      a normalized protocol which allows the rapid analysis of a large number of
      potential cell binding substrates using polymer microarrays and high-content
      fluorescence microscopy. The method was successfully applied to the discovery of
      optimal polymer substrates from a 214-member polyurethane library with mouse
      fibroblast cells (L929), as well as simultaneous evaluation of cell viability and
      cellular morphology. Analysis demonstrated high biocompatibility of the binding
      polymers and permitted the identification of several different cellular
      morphologies, showing that specific polymer interactions may provoke changes in
      cell shape. In addition, SAR studies showed a clear correspondence between
      cellular adhesion and polymer structure. The approach can be utilized to perform
      multiple experiments (up to 1024 single experiments per slide) in a highly
      reproducible manner, leading to the generation of vast amounts of data in a short
      time period (48-72 h) while reducing dramatically the quantities of polymers,
      reagents and cells used.

PMID- 18708703
TI  - Analysis of explanted ePTFE cardiovascular grafts (modified BT shunt).
AB  - Structural, chemical, mechanical and surface changes were studied in expanded
      polytetrafluroethylene vascular grafts explanted from children undergoing planned
      surgical management of congenital heart disease. These grafts were implanted when
      recipients were aged 7 days to 8 years (median--48 weeks) and they had been in
      circulation for a period of 10-52 months (median--74 weeks). While no chemical
      changes were observed in the shunt, on average the tensile strength had decreased
      by 50%, total elongation by 61% and crystallinity by 3%. No salt deposits were
      observed on the surface of the graft. Soluble and insoluble proteins were bound
      to the polymer surface, which had made the surface hydrophilic. The external
      surface roughness had increased by 254.5 and the internal surface roughness by
      2.6 times the initial value. The fine polymer structure had become fused and
      clumped. The fusing of strands on the polymer surface became more pronounced with
      longer duration of implantation. In one instance of previously documented graft
      stenosis, the heat capacity was found to be more than that of the unimplanted
      sample, indicating an increase in crystallinity. A longer period of study with a
      larger sample size would likely shed more light on the relation between physico
      chemical changes and graft stenosis.

PMID- 18708704
TI  - Models for the histologic study of the skin interface with percutaneous
      biomaterials.
AB  - Percutaneous devices are critical for health care. Access to tissue, vessels and
      internal organs afforded by these devices provides the means to treat and monitor
      many diseases. Unfortunately, such access is not restricted, and infection may
      compromise the usefulness of the device and even the life of the patient. New
      biomaterials offer the possibility of maintaining internal access while limiting
      microbial access, but understanding of the cutaneous/biomaterial interface and
      models to study this area are limited. This paper focuses on models useful for
      studying the morphology and biology of the intersection of skin and percutaneous
      biomaterials. An organ culture and a mouse model are described that offer
      promising possibilities for improved understanding of this critical interface.

PMID- 18708705
TI  - Modelling of heat and mass transfer processes in neonatology.
AB  - This paper reviews some of our recent applications of computational fluid
      dynamics (CFD) to model heat and mass transfer problems in neonatology and
      investigates the major heat and mass transfer mechanisms taking place in medical
      devices such as incubators and oxygen hoods. This includes novel mathematical
      developments giving rise to a supplementary model, entitled infant heat balance
      module, which has been fully integrated with the CFD solver and its graphical
      interface. The numerical simulations are validated through comparison tests with
      experimental results from the medical literature. It is shown that CFD
      simulations are very flexible tools that can take into account all modes of heat
      transfer in assisting neonatal care and the improved design of medical devices.

PMID- 18708706
TI  - Carbon microelectromechanical systems as a substratum for cell growth.
AB  - The study of the biocompatible properties of carbon microelectromechanical
      systems (carbon-MEMS) shows that this new microfabrication technique is a
      promising approach to create novel platforms for the study of cell physiology.
      Four different types of substrates were tested, namely, carbon-MEMS on silicon
      and quartz wafers, indium tin oxide (ITO) coated glass and oxygen-plasma-treated
      carbon thin films. Two cell lines, murine dermal fibroblasts and neuroblastoma
      spinal cord hybrid cells (NSC-34) were plated onto the substrates. Both cell
      lines showed preferential adhesion to the selectively plasma-treated regions in
      carbon films. Atomic force microscopy and Fourier transform infrared spectroscopy
      analyses demonstrated that the oxygen-plasma treatment modifies the physical and
      chemical properties of carbon, thereby enhancing the adsorption of extracellular
      matrix-forming proteins on its surface. This accounts for the differential
      adhesion of cells on the plasma-treated areas. As compared to the methods
      reported to date, this technique achieves alignment of the cells on the carbon
      electrodes without relying on direct patterning of surface molecules. The results
      will be used in the future design of novel biochemical sensors, drug screening
      systems and basic cell physiology research devices.

PMID- 18708707
TI  - Leveraging liquid dielectrophoresis for microfluidic applications.
AB  - Miniaturized fluidic systems have been developed in recent years and offer new
      and novel means of leveraging the domain of microfluidics for the development of
      micro-total analysis systems (microTAS). Initially, such systems employed closed
      microchannels in order to facilitate chip-based biochemical assays, requiring
      very small quantities of sample and/or reagents and furthermore providing rapid
      and low-cost analysis on a compact footprint. More recently, advancements in the
      domain of surface microfluidics have suggested that similar low volume sample
      handling and manipulation capabilities for bioassays can be attained by
      leveraging the phenomena of liquid dielectrophoresis and droplet
      dielectrophoresis (DEP), without the need for separate pumps or valves. Some of
      the key aspects of this surface microfluidic technology and its capabilities are
      discussed and highlighted in this paper. We, furthermore, examine the integration
      and utility of liquid DEP and droplet DEP in providing rapid and automated sample
      handling and manipulation capabilities on a compact chip-based platform.

PMID- 18708708
TI  - Methods in cell separation for biomedical application: cryogels as a new tool.
AB  - The analysis and separation of cells including rare cell populations from a
      heterogeneous population has become an important tool in scientific research and
      medicine. The last two decades have seen tremendous progress in the field of cell
      separation, as a result of which various methods have been available which
      utilize different physiochemical and immunological characteristics of cells. A
      brief overview of methods of cell separation used in the past and a detailed
      description of methods being used presently as well as prospective methods are
      discussed in the paper. Chromatography has come into the picture as the apparent
      solution for the limitations of various cell separation methods. In recent years,
      a new and promising affinity-based cell separation chromatography technique has
      been developed using highly interconnected supermacroporous cryogels, and this
      new method is discussed in detail. Due to the importance and relevance of cell
      based therapy and stem cell separation in the present scenario, cryogels present
      a new tool for preparative scale cell separation.

PMID- 18708709
TI  - Semi-interpenetrating polymer networks composed of silk fibroin and poly(ethylene
      glycol) for wound dressing.
AB  - Semi-interpenetrating polymer networks (SIPNs) composed of silk fibroin (SF) and
      poly(ethylene glycol) (PEG) were prepared by photopolymerization of a PEG
      macromer in the presence of SF to improve the mechanical properties of SF sponge
      as wound dressing. The morphological structure of the SF/PEG SIPNs was observed
      to be composed of an interconnected microporous surface and a cross-sectional
      area. SF/PEG SIPNs showed non-cytotoxicity evaluated by a cell proliferation
      method using L929 fibroblasts. Wound contraction treated with SF/PEG SIPNs
      sponges was faster than that of Vaseline gauze as a control. Histological
      observation confirmed that the deposition of collagen in the dermis was organized
      by covering the wound area with SF/PEG SIPNs. The above results indicated that
      SF/PEG SIPNs could be used as wound dressing.

PMID- 18708710
TI  - Tissue bionics: examples in biomimetic tissue engineering.
AB  - Many important lessons can be learnt from the study of biological form and the
      functional design of organisms as design criteria for the development of tissue
      engineering products. This merging of biomimetics and regenerative medicine is
      termed 'tissue bionics'. Clinically useful analogues can be generated by
      appropriating, modifying and mimicking structures from a diversity of natural
      biomatrices ranging from marine plankton shells to sea urchin spines. Methods in
      biomimetic materials chemistry can also be used to fabricate tissue engineering
      scaffolds with added functional utility that promise human tissues fit for the
      clinic.

PMID- 18708711
TI  - Isolation, culture and adenoviral transduction of parietal cells from mouse
      gastric mucosa.
AB  - Here we describe a method for the isolation of intact gastric glands from mice
      and primary culture and transfection of mouse gastric epithelial cells.
      Collagenase digestion of PBS-perfused mouse stomachs released large intact
      gastric glands that were plated on a basement membrane matrix. The heterogeneous
      gland cell cultures typically contain approximately 60% parietal cells. Isolated
      mouse parietal cells remain viable in culture for up to 5 days and react strongly
      with an antibody specific to the gastric H(+)/K(+) ATPase. Isolated intact mouse
      gastric glands and primary cultures of mouse parietal cells respond to the
      secretagogue, histamine. Typical morphological changes from a resting to an acid
      secreting active parietal cell were observed. In resting cultures of mouse
      parietal cells, the H(+)/K(+) ATPase displayed a cytoplasmic punctate staining
      pattern consistent with tubulovesicle element structures. Following histamine
      stimulation, an expansion of internal apical vacuole structures was observed
      together with a pronounced redistribution of the H(+)/K(+) ATPase from the
      cytoplasm to the apical vacuoles. A reproducible procedure to express genes of
      interest exogenously in these cultures of mouse parietal cells was also
      established. This method combines recombinant adenoviral transduction with
      magnetic field-assisted transfection resulting in approximately 30% transduced
      parietal cells. Adenoviral-transduced parietal cells maintain their ability to
      undergo agonist-induced activation. This protocol will be useful for the
      isolation, culture and expression of genes in parietal cells from genetically
      modified mice and as such will be an invaluable tool for studying the complex
      exocytic and endocytic trafficking events of the H(+)/K(+) ATPase which underpin
      the regulation of acid secretion.

PMID- 18708712
TI  - Application of molecular methods for monitoring transmission stages of malaria
      parasites.
AB  - Recent technical advances in malaria research have allowed specific detection of
      mRNA of genes that are expressed exclusively in sexual stages (gametocytes) of
      malaria parasites. The specificity and sensitivity of these techniques were
      validated on cultured laboratory clones of both human malaria parasites
      (Plasmodium falciparum) and rodent parasites (P. chabaudi). More recently,
      quantitative molecular techniques have been developed to quantify these sexual
      stages and used to monitor gametocyte dynamics and their transmission to
      mosquitoes. Molecular techniques showed that the infectious reservoir for malaria
      is larger than expected from previous microscopic studies; individual parasite
      genotypes within an infection can simultaneously produce infectious gametocytes;
      gametocyte production can be sustained for several months, and is modulated by
      environmental factors. The above techniques have empowered approaches for in
      depth analysis of the biology of the transmission stages of the parasite and
      epidemiology of malaria transmission.

PMID- 18708713
TI  - Nafcillin-loaded PLGA nanoparticles for treatment of osteomyelitis.
AB  - The goal of this investigation is to develop poly(DL-lactide-co-glycolide) (PLGA)
      nanoparticles for the delivery of antibiotics such as nafcillin to osteoblasts.
      This is important in order to treat Staphylococcus aureus-mediated osteomyelitis.
      The latter is often chronic and highly resistant to antibiotics. Nafcillin (a
      penicillinase-resistant penicillin)-loaded nanoparticles were prepared by a
      single emulsion/solvent evaporation method. In vitro drug release studies were
      conducted in an incubator shaker at 37 degrees C in phosphate buffer saline. Drug
      loading and release were determined by UV-Vis spectroscopy. A viability study was
      conducted in S. aureus-infected mouse osteoblasts. In vitro release study showed
      an initial burst release and a second phase of slow release. Following 24 and 48
      h of incubation, all formulations of nanoparticles loaded with nafcillin either
      killed or significantly reduced all of the intracellular bacteria. Our data
      demonstrate that effective killing of intracellular S. aureus is possible by
      treating the infected osteoblasts with nanoparticles loaded with nafcillin.

PMID- 18708714
TI  - Measurement of X-ray rocking curves in the Bragg-Laue case.
AB  - X-ray rocking curves in the Bragg-Laue case diffracting from the side surface of
      a plane-parallel crystal have been measured using a high-resolution optical
      system. The full width at half-maximum of the rocking curves is approximately
      three times narrower than that measured from the top surface. The characteristics
      of the transmitted beam from the side surface are almost the same as those
      through a thin crystal in the Bragg case. The rocking curves and the direction of
      X-ray energy flow in the crystal observed in the experiment can be reproduced
      using Wagner's approach [Wagner (1956), Z. Phys. 146, 127-168].

PMID- 18708715
TI  - The (Fo-Fc) Fourier synthesis: a probabilistic study.
AB  - (F(o)-F(c)) and (2F(o)-F(c)) Fourier syntheses are considered the most powerful
      tools for recovering the remainder of a structure and for correcting crystal
      structure models. A probabilistic approach has been applied to derive the formula
      for the variance for the expected value of the coefficient (F(o)-F(c)). This has
      allowed a better understanding of the features of the difference Fourier
      synthesis; in particular, a subset of well phased reflections has been separated
      from the subset of reflections best phased by the standard F(o) Fourier
      synthesis. An iterative procedure, based on the electron-density modification of
      the difference Fourier map, has been devised which aims to improve phase and
      modulus estimates of the reflections with higher variance value, by using as
      lever arm the set of reflections with lower variance value. The new procedure
      (DEDM) has been implemented and verified on a wide set of test structures, the
      partial models of which were obtained by molecular replacement or by automatic
      model-building routines applied to experimental electron-density maps. Phase and
      modulus estimates of the difference Fourier syntheses improve in all the test
      cases; as a consequence, the quality of the difference Fourier maps also improves
      in the region where the target structure deviates from the partial model. A new
      procedure is suggested, combining DEDM with standard electron-density
      modification techniques, which leads to significant reduction of the phase
      errors. The procedure may be considered a starting point for further
      developments.

PMID- 18708716
TI  - The symmetry of HK codes representing close-packed structures and the efficient
      generation of non-equivalent polytypes of a given length.
AB  - The HK representation of close-packed polytypes is studied as a binary code. It
      is shown that the HK code can be seen as operators forming a group. The
      neutrality condition is then translated to HK sequences that result in the
      identity operator. The symmetry of an HK word can be related to the space-group
      symmetry of the corresponding polytype. All HK code types corresponding to all
      possible close-packed space groups are reported. From a coding perspective,
      equivalent HK codes correspond to bracelet equivalent classes. An efficient
      algorithm with execution time constant per generated object is modified to
      generate all non-equivalent polytypes of a given length.

PMID- 18708717
TI  - Stacking and twin faults in close-packed crystal structures: exact description of
      random faulting statistics for the full range of faulting probabilities.
AB  - The classical model of independent random single deformation faults and twin
      faulting in face-centered-cubic and hexagonal close packing is revisited. The
      model is extended to account for the whole range of faulting probabilities. The
      faulting process resulting in the final stacking sequences is described by
      several equivalent computational models. The probability sequence tree is
      established. Random faulting is described as a finite-state automaton machine. An
      expression giving the percent of hexagonality from the faulting probabilities is
      derived. The average sizes of the cubic and hexagonal domains are given as a
      function of single deformation and twinning fault probabilities. An expression
      for the probability of finding a given sequence within the complete stacking
      arrangement is also derived. The probability P(0)(Delta) of finding two layers of
      the same type Delta layers apart is derived. It is shown that previous
      generalizations did not account for all terms in the final probability
      expressions. The different behaviors of the P(0)(Delta) functions are discussed.

PMID- 18708718
TI  - X-ray and gamma-ray propagation in bent crystals with flat and cylindrical
      surfaces.
AB  - In this paper, X-ray and gamma-ray propagation in crystals having a constant
      strain gradient and flat or cylindrical surfaces is investigated. When a
      displacement field is present, the Takagi-Taupin equations are solved either by
      the Riemann-Green method or by a numerical method. The results are applied to
      study the operation of a double-crystal Laue-Laue diffractometer having a flat
      collimating crystal followed by a bent analyzer crystal. In particular, the
      effect of the analyzer strain on the location of the diffraction peaks in the
      dispersive and non-dispersive set-up is examined, thus confirming the previously
      reported peak location as being set only by the diffracting-plane spacing on the
      analyzer entrance surface.

PMID- 18708719
TI  - The triplet invariant revisited.
AB  - It is shown that the formula for the positivity of the triplet invariant in P
      1bar changes drastically if one uses a different statistical method by imposing
      acceptable and unbiased additional structural information. We obtain a much lower
      probability for the strength (almost (1/2)) of the triplet formula than the
      classical one.

PMID- 18708720
TI  - The quartet revisited.
AB  - Using an unbiased and very general joint density of the atomic position vectors
      we are able to calculate different probabilities for the sign of the quartet
      given its second neighborhood. One already knows that additional chemical
      information alters the joint probability distribution (j.p.d.) of structure
      factors. That is, they can and will give different j.p.d.'s for the quartet
      invariant given its second neighborhood. In this paper we show that even without
      additional chemical information the j.p.d.'s of structure factors can be strongly
      different from the classical ones if we impose a general j.p.d. for the atomic
      vectors based on the fact that the real distribution of the atomic position
      vectors is a sum of delta functions.

PMID- 18708721
TI  - A statistical interpretation of the triplet and quartet invariant in P1. A
      theoretical discussion.
AB  - We present a method that we call symbolic asymptotic development (SAD) to obtain
      joint probability distributions (j.p.d.'s) of phases of structure factors for
      general even densities of the atomic position vectors. The formula for the
      triplet and quartet invariant that we obtain in this way reduces to the well
      known classical formula for the case of a uniform density of the atomic position
      vectors. For the case of complete knowledge of the atomic vectors it reduces to
      first order to the exact probability density of the triplet (quartet) phase
      invariant. Applying this formula to the most general j.p.d. of the atomic vectors
      we obtain a statistical interpretation of Hauptman's algebraic B(3,0) and B(4,0)
      formulas. We also give a heuristic derivation of the SAD method. Another method
      that we shall discuss uses a method called linearization of the invariants that
      also produces formulas for the triplet phase invariant. This method is based on
      previous work and is also more laborious to calculate with than the SAD method.
      It can also give a statistical interpretation of the B(3,0) formula. We show that
      the formula obtained for the triplet resembles the formula obtained with SAD.

PMID- 18708722
TI  - Determination of the electrostatic potential and electron density of silicon
      using convergent-beam electron diffraction.
AB  - A structure-analysis method using convergent-beam electron diffraction (CBED)
      developed by Tsuda et al. [Tsuda & Tanaka (1999), Acta Cryst. A55, 939-954;
      Tsuda, Ogata, Takagi, Hashimoto & Tanaka (2002), Acta Cryst. A58, 514-525] has
      been applied to the determination of the electrostatic potential and electron
      density of crystalline silicon. CBED patterns recorded at nine different
      incidences are simultaneously used to improve the accuracy of the refinement. The
      Debye-Waller factor and low-order structure factors of silicon have been
      successfully refined only using CBED data. The electrostatic potential and
      electron-density distribution have been reconstructed from the refined
      parameters. The latter clearly shows the bonding electrons between the nearest
      neighbor atoms. The obtained results are compared with the results of other CBED
      and recent X-ray diffraction experiments. The influence of the number of refined
      low-order structure factors on the electron density is discussed. The effect of
      the reduction of experimental data points on the accuracy of the refined
      parameters is also examined.

PMID- 18708723
TI  - On model-free reconstruction of lattice dynamics from thermal diffuse scattering.
AB  - Expressions are derived for thermal diffuse scattering (TDS) using a formalism
      based on Born's S-matrix. It is shown that for monoatomic crystals the dynamical
      matrix containing the full information on lattice dynamics can be recovered from
      one-phonon TDS intensities. For any non-monoatomic crystal, part of the
      information is always lost in the kinematic approximation, but can in principle
      be recovered by measuring TDS in the dynamical scattering regime. In the long
      wave limit the description here coincides with known results.

PMID- 18708725
TI  - Cells tissues organs. Introduction.

PMID- 18708724
TI  - Correlation of matrix metalloproteinases and tissue inhibitors of matrix
      metalloproteinase expression in ileal carcinoids, lymph nodes and liver
      metastasis with prognosis and survival.
AB  - PURPOSE: Ileal carcinoids are gut epithelial tumors originating from serotonin
      containing enterochromaffin (EC) cells. Therapeutic options for effectively
      inhibiting the growth and spread of metastatic carcinoids are still limited. We
      aimed to identify the role of matrix metalloproteinases (MMPs) and their
      endogenous tissue inhibitors (TIMPs) during tumor development and metastasis.
      PATIENTS AND METHODS: Tissue samples were obtained from surgically treated
      patients. Expression of the EC-cell marker, vesicular monoamine transporter-1
      (VMAT-1), was used to verify ileal carcinoids. We investigated the differential
      expression of MMP-2, 7, 9, 11, and 13 and their endogenous inhibitors (TIMP-1, 2,
      and 3) by quantitative real-time RT-PCR in 25 primary tumors, their corresponding
      lymph node metastases and/or liver metastases and matched normal mucosa. RESULTS:
      Significantly increased expression of VMAT-1, MMP-2, MMP-11, TIMP-1 and TIMP-3
      was determined by quantitative RT-PCR in EC-cell carcinoids compared to normal
      intestinal mucosa (p < 0.05). In contrast, MMP-2 and MMP-9 as well as TIMP-1,
      TIMP-2, and TIMP-3 expression in primary tumors of patients with liver metastases
      (M1) was significantly lower than in patients lacking liver metastases (M0). EC
      cell tumors were significantly larger in the M1 group of tumors, while VMAT-1
      expression was significantly decreased. We found an inverse correlation between
      tumor size and prognosis. Univariate analysis further revealed that decreased
      expression of VMAT-1, MMP-2 and TIMP-3 in primary tumors was significantly
      associated with a reduced survival time of the patients. CONCLUSION: Our data
      reveal that MMP-2 and TIMP-3 expression together with VMAT-1 expression are of
      potential prognostic and clinical value in ileal carcinoids.

PMID- 18708726
TI  - Abstracts of the 4th International Stroke Summit, Nanjing, China, July 25-27,
      2008.

PMID- 18708727
TI  - Formula-based estimates of the GFR: equations variable and uncertain.
AB  - Regarding the prevalence of chronic kidney disease in the population, estimation
      of glomerular filtration rate is of importance. Creatinine-based formulas are
      thus useful as the first step of a prevention strategy. Several creatinine-based
      formulas have been published. Among these, the Cockcroft-Gault formula and the
      Modification of Diet in Renal Disease (MDRD) study equation are the most used by
      physicians. The latter may be automatically reported by laboratories and has thus
      great success. However, these formulas have limitations. First, the MDRD formulas
      are not applicable to all populations, notably the healthy one and the patients
      with abnormal weight (anorectic or obese). Second, we evoke the limitations in
      the precision of the formulas linked to analytical aspects. Indeed, these
      analytical limitations remain significant even if they are improved by creatinine
      standardization. Lastly, we briefly mention the potential impact of these
      limitations on the epidemiology and the staging of chronic kidney disease.

PMID- 18708728
TI  - Morphology of glomerular hematuria is reproduced in vitro by carbonyl stress.
AB  - BACKGROUND: In glomerulonephritides, dysmorphic red blood cells (RBCs) with
      membrane blebs can be found in the urine; this is referred to as glomerular
      hematuria. Glomerulonephritides are characterized by increased carbonyl stress
      and elevated methylglyoxal (MGO) levels. MGO causes oxidative stress and
      intracellular calcium accumulation. In the present study, we investigated whether
      the effect of MGO-induced calcium accumulation in RBCs develops through increased
      oxidative stress. Furthermore, we studied whether MGO can lead to RBC membrane
      blebbing. METHODS: RBC suspensions from healthy volunteers were incubated with
      different concentrations of MGO at 37 degrees C. We measured oxidative stress and
      intracellular calcium level using fluorescent indicators. We determined the
      frequency of dysmorphic RBCs, and also performed scanning electron microscopy.
      RESULTS: MGO increased oxidative stress and caused accumulation of calcium in
      isolated RBCs. These effects could be prevented using antioxidants. In the
      presence of MGO, RBC membrane blebbing developed. CONCLUSION: According to our
      findings, MGO causes calcium accumulation through oxidative stress. Carbonyl and
      oxidative stress may play an important role in the formation of dysmorphic RBCs
      in glomerular hematuria.

PMID- 18708729
TI  - Response to reintroduction of cetuximab in 5 patients with advanced, chemotherapy
      resistant, colorectal cancer without progressive disease following first-line
      therapy with a cetuximab-containing regimen.
AB  - OBJECTIVE: We aimed to determine the response to cetuximab in advanced,
      chemotherapy-resistant, colorectal cancer following successful first-line therapy
      with the antibody. METHODS: Five patients with metastatic colorectal cancer were
      treated with a cetuximab-containing regimen after failure of several conventional
      chemotherapies. RESULTS: These patients had been successfully treated with
      cetuximab as first-line therapy, and the antibody was then discontinued without
      disease progression. No severe toxicities were observed upon reexposure to
      cetuximab. Partial response was noted in 1 patient and tumor stabilization in 2
      patients. CONCLUSION: Reintroduction of cetuximab in combination with
      chemotherapy is safe and efficacious in patients with colorectal cancer whose
      tumors were not refractory to a prior cetuximab-containing therapy.

PMID- 18708730
TI  - Serrated adenoma of the colorectum undergoes a proliferation versus
      differentiation process: new conceptual interpretation of morphogenesis.
AB  - OBJECTIVE: Serrated adenoma (SA) consists of glands both with intraluminal
      projection of tall columnar cells, which resemble the terminally differentiated
      cells in the surface epithelium, and with concave short cells, which resemble
      progenitor crypt cells of the colon. The aim of this study was to clarify the
      relationship between the serrated architecture and proliferation/differentiation
      process in SAs. METHODS: The expressions of both terminally differentiated
      markers, such as p21, cytokeratin 20 and carbonic anhydrase I, and
      progenitor/proliferative markers, such as beta-catenin, CD44 and Ki-67, were
      immunohistochemically examined in 43 SAs and 20 tubular adenomas. RESULTS: P21
      positive cells were more abundant in SAs than in tubular adenomas. Cytokeratin 20
      and carbonic anhydrase I expressions were confined to the tall cells, while
      nuclear beta-catenin and CD44 were expressed in the short cells in SAs. The Ki-67
      labeling indices were significantly lower in tall cells than in short ones.
      CONCLUSIONS: SAs might undergo both proliferation and terminal differentiation,
      which is associated with unique serrated configuration.

PMID- 18708731
TI  - Protein-bound polysaccharide K partially prevents apoptosis of circulating T
      cells induced by anti-cancer drug S-1 in patients with gastric cancer.
AB  - BACKGROUND AND METHODS: It has been shown that T-cell dysfunction, including
      apoptosis of peripheral blood T cells, commonly occurs in patients receiving
      chemotherapy. In order to evaluate whether concomitant administration of the oral
      biological response modifier protein-bound polysaccharide K (PSK) could induce
      anti-apoptotic effects in patients treated with the anti-cancer drug, S-1,
      peripheral blood T cells were analyzed for induction of apoptosis, caspase-3
      activities and expression of proapoptotic protein Bax and anti-apoptotic protein
      Bcl-2 in patients with curatively resected stage III gastric cancer, who were
      randomly assigned to postoperative adjuvant therapy with S-1 alone (n = 10) or S
      1 combined with PSK (n = 10). RESULTS: T-cell apoptosis 5 weeks after adjuvant
      therapy was significantly higher in the S-1 group (24.1 +/- 5.0%) than in the S-1
      + PSK group (19.1 +/- 3.9%). S-1 induced T-cell apoptosis and concomitantly
      elevated caspase-3 activities and Bax expression in peripheral blood T cells. In
      addition, PSK partially prevented the T-cell apoptosis induced by S-1.
      CONCLUSION: PSK could partially prevent the T-cell apoptosis induced by S-1.

PMID- 18708732
TI  - Targeting Her-2/neu in breast cancer: as easy as this!
AB  - Her-2/neu-positive tumors account for approximately 20% of all breast cancer and
      these tumors carry poor prognosis. Trastuzumab and lapatinib are 2 agents that
      have gained FDA approval for treating Her-2/neu-positive breast cancer.
      Trastuzumab has been shown to improve all endpoints when added to chemotherapy
      compared to chemotherapy alone, both in the adjuvant and metastatic phases. The
      addition of lapatinib to capecitabine has recently been shown to improve time to
      progression in trastuzumab-refractory patients with unique activity against brain
      metastasis. In spite of their impressive results, a significant fraction of
      patients still develop either primary or secondary resistance, a fact that
      entails the discussion of possible mechanisms of resistance. Biomarkers including
      PTEN, p95HER2, IGF1R and others have been linked to response to Her-2/neu
      targeting agents. In this article, we overview the Her-2/neu signaling pathways
      and how a better understanding of the different molecular aspects of this
      oncogene could serve in optimizing the use of Her-2/neu-targeting agents. We also
      discuss the preclinical and clinical data of these biomarkers that may guide
      clinicians in choosing the right drug whenever possible.

PMID- 18708733
TI  - Effects of VEGF on the blood-brain barrier disruption caused by hyperosmolarity.
AB  - This study was performed to test whether disruption of the blood-brain barrier
      (BBB) caused by hyperosmolarity could be related to vascular endothelial growth
      factor (VEGF), using anti-VEGF antibody and ciclopirox olamine (CPX), an inducer
      of VEGF. CPX 50 mg/kg or normal saline was given intraperitoneally to male Wistar
      rats 18 h before BBB disruption. Two craniotomies were made on the ipsilateral
      cortex (IC-1 and IC-2) where the BBB would be disrupted, and a third hole was
      made on the contralateral cortex (CC) to expose the cortices. We applied normal
      saline (to IC-1 and the CC) or anti-VEGF antibody (to IC-2) for 90 min before BBB
      disruption with intracarotid injection of 25% mannitol. The degree of BBB
      disruption was determined by measuring the transfer coefficient (K(i)) of (14)C
      alpha-aminoisobutyric acid and the volume of (3)H-dextran distribution. The
      protein levels of VEGF were determined with Western blot analysis. In the control
      animals, hyperosmolar mannitol significantly increased (415%) the K(i) in IC-1.
      The K(i) was attenuated with anti-VEGF antibody application (-28%, p < 0.05).
      Even though the protein levels of VEGF were strongly increased with CPX
      pretreatment, this upregulation did not alter the hyperosmolar BBB disruption in
      the saline- or in the antibody-treated cortex. The data on the volume of dextran
      distribution followed the same pattern as that of the K(i) but without a
      statistically significant difference between IC-1 and IC-2 in either group. Our
      data demonstrated that hyperosmolar BBB disruption could be attenuated with anti
      VEGF antibody. However, upregulation of VEGF with CPX did not alter the degree of
      hyperosmolar BBB disruption with or without anti-VEGF antibody treatment. This
      study suggests that the contribution of VEGF in hyperosmolar BBB disruption is
      limited.

PMID- 18708734
TI  - Pneumothorax.
AB  - Pneumothorax represents a common clinical problem. An overview of relevant and
      updated information on epidemiology, pathophysiology, and management of
      spontaneous (primary and secondary), catamenial, and traumatic (iatrogenic and
      noniatrogenic) pneumothorax is given.

PMID- 18708735
TI  - Can pleural tuberculosis be diagnosed using interferon-gamma release assays?

PMID- 18708736
TI  - Old meets modern: the use of traditional cryoprobes in the age of molecular
      biology.
AB  - BACKGROUND: Endobronchial forceps biopsies are often small and are associated
      with a relevant extent of artifacts. To overcome these limitations is an
      important task. Especially when considering predictive factors for
      pharmacological therapies of lung cancer (ERCC1, RRM1) a development of biopsy
      techniques seems to be essential. This is the first report on a new endobronchial
      biopsy technique called cryobiopsy. OBJECTIVES: In this study the feasibility and
      the potential advantages of applying cryoprobes for harvesting samples for
      histological examination in flexible bronchoscopies will be focused on. METHODS:
      In 12 patients suffering from exophytic endobronchial malignancies, a modified
      flexible cryoprobe was used for immediate recanalization. The extracted tissue
      was examined histologically regarding sample quality and sample size. RESULTS:
      Tissue samples obtained using the cryoprobe showed an extraordinary good quality
      in terms of size (median diameter of 6.7 mm, range 4.2-13 mm) and artifact-free
      sample area (75% of the samples showed an artifact-free sample area of more than
      75%). Additionally molecular markers were shown to be well preserved.
      CONCLUSIONS: The new technique termed cryobiopsy might widen the chest
      physician's range of tools for diagnostic bronchoscopies.

PMID- 18708737
TI  - Conventional and early loading of two-implant supported mandibular overdentures.
      A systematic review.
AB  - OBJECTIVES: Implant loading time is considered to influence the treatment
      outcomes. Number of experimental studies have shown that implant loading up to 3
      months can produce equally satisfactory results. However, research results in
      this area are not consistent. The purpose of the study was to investigate the
      influence of conventional and early loading of two-implant supported mandibular
      overdentures on treatment outcomes. METHODS: The articles from 1985 to 2007 in
      English related to the topic were identified. Totally 221 (214 online and 7
      printed) primary articles were detected. Eight articles were selected for data
      extraction. Implant survival and success rates, periimplant parameters,
      prosthetic maintenance and patient satisfaction were considered. RESULTS: Implant
      success rate ranged from 83% to 100% in conventional loading group and from 71%
      to 100% in early loading group. During the first year in conventional group, the
      marginal bone loss ranged from 0.35 to 0.91 mm, during the second year--from zero
      to 0.2 mm, whereas in early loading group these intervals were 0.12-1 mm and 0
      0.15 mm, respectively. Comparing averaged probing depth values at different time
      periods, it could be noticed that around conventionally loaded implants probing
      depth slightly decreased (from 1.62 mm to 1.56 mm), while around early loaded
      implants--increased from 1.7 mm to 1.82 mm. CONCLUSIONS: Considering implant
      success rates and peri-implant parameters early loading protocol produces equal
      outcomes as with conventional loading. More well designed studies are needed to
      further substantiate the early loading protocol.

PMID- 18708738
TI  - Barx1, growth factors and apoptosis in facial tissue of children with clefts.
AB  - OBJECTIVE: Clefts of lip and palate belong to the most common birth defects
      worldwide. Growth factors and genes play an important role in tissue growth,
      differentiation and induction and upregulation of growth factors, apoptosis and
      matrix metalloproteinases might be involved in pathogenesis of facial clefts. The
      aim of this study was investigation of palate tissue in children with unilateral
      cleft lip palate for detection of local tissue growth factors, barx1 and
      apoptosis. MATERIALS AND METHODS: We investigated soft and hard palate tissue
      from 36 children with complete unilateral cleft lip and palate from cleft area.14
      children were in age before and primary dentition, but 22 children were in mixed
      dentition period. We examined the localization of barx1, FGFR1, NGFR, TGFbeta,
      BMP2/4, MMP2, PGP 9,5 by immunohistochemistry. TUNEL method was performed for
      detection of apoptotic cells. RESULTS: Abundance of FGFR1 positive cells was seen
      almost in all cases. FGFR richly stained cells of soft and hard palate tissue.
      Abundance of NGFR positive cells was detected in basal epithelium, hair
      follicles, nerve fibers in wall of blood vessels and subepithelium, and was more
      often seen in children before mixed dentition. TGFbeta has showed intensive
      expression in epithelium, cartilage and bone in both dentition ages.
      Chondrocytes, fibroblasts and macrophages expressed MMP2 predominant before mixed
      dentition. Regional expression of barx1 was observed in epithelium before the
      mixed dentition, while during mixed dentition gene appeared in hyaline cartilage.
      TUNEL discovered apoptosis in both dentition ages. CONCLUSIONS: FGFR1 and TGFbeta
      are main tissue stimulating growth factors in both dentition ages. Expression of
      barx1 appears in cleft lip palate affected structures mainly in mixed dentition
      ages. NGFR and neuropeptides-containing structures are mainly characteristic in
      cleft tissue before mixed dentition. Distribution of genes, GF and apoptosis seem
      to correlate rather with dentition age than to type of CLP.

PMID- 18708739
TI  - Creating three-dimensional tooth models from tomographic images.
AB  - The use of Finite Element Analysis (FEA) is becoming very frequent in Dentistry.
      However, most of the three-dimensional models presented by the literature for
      teeth are limited in terms of geometry. Discrepancy in shape and dimensions can
      cause wrong results to occur. Sharp cusps and faceted contour can produce stress
      concentrations, which are incoherent with the reality. AIM: The aim of this study
      was the processing of tomographic images in order to develop an advanced three
      dimensional reconstruction of the anatomy of a molar tooth and the integration of
      the resulting solid with commercially available CAD/CAE software. METHODS:
      Computed tomographic images were obtained from 0.5 mm thick slices of mandibular
      molar and transferred to commercial cad software. Once the point cloud data have
      been generated, the work on these points started to get to the solid model of the
      tooth with Pro/Engineer software. RESULTS: The obtained tooth model showed very
      accurate shape and dimensions, as it was obtained from real tooth data with error
      of 0.0 to -0.8 mm. CONCLUSION: The methodology presented was efficient for
      creating a biomodel of a tooth from tomographic images that realistically
      represented its anatomy.

PMID- 18708740
TI  - Relationship between mandibular cortical bone height and bone mineral density of
      lumbar spine.
AB  - The aim of this study was to evaluate the association between lumbar spine bone
      mineral density and mandible cortical bone height at the mental foramen and at
      the angle of the jaw. PATIENTS AND METHODS: A total of 130 women living in
      Lithuania, were examined. None of the participants were known to have endocrine,
      metabolic or skeletal disorders. Bone mineral density (BMD) was measured in the
      spine lumbar area L2-L4. The mandibles were examined on panoramic x-ray images.
      On each radiograph cortical thickness of mandible was measured at the mental
      foramen and at the angle of the jaw. The results demonstrated a tendency of high
      probability of osteoporosis in cases were radiomorphometric parameters are low.
      There was a significant difference between bone mineral density of lumbar spine
      and cortical bone height of mandible below the foramen mentale and at the angle
      of the jaw (p<0.01).

PMID- 18708741
TI  - Caries experience in relation to oral hygiene, salivary cariogenic microflora,
      buffer capacity and secretion rate in 6-year olds and 12 year olds in Riga.
AB  - OBJECTIVE: The aim was to assess possible relationship between oral hygiene,
      salivary cariogenic microflora, buffer capacity, secretion rate and caries
      experience in 6 year olds and 12 year olds in Riga, and to evaluate these
      variables in relation to caries risk. MATERIALS AND METHODS: 50 children aged 6
      and 71 children aged 12 were examined clinically and by bitewing X-ray for caries
      diagnosis. Green-Vermillion oral hygiene index, stimulated salivary flow rate and
      buffer capacity were estimated (CRT-buffer; Ivoclar, Vivadent, Liechtenstein).
      Salivary mutans streptococci (MS) and lactobacilli (LB) (CRT-bacteria; Vivadent)
      were determined only for children with dmft/DMFT>4: 60% at age of 6, 54,9% at age
      of 12. All data were statistically analyzed using frequency tables, Pearson
      chi2test and ANOVA analysis. RESULTS: Mean DMFT was 0.12 in 6 year olds, and 4.6
      in 12 year olds. Mean Green-Vermillion index was 0.75 in 6 year olds and 0.99 in
      12 year olds. Caries experience and Green-Vermillion index were associated only
      in 6 year olds (p=0.024). Salivary MS was associated with Green-Vermillion index
      only in 12 year olds (p=0.086). Salivary MS and caries experience were associated
      only in 12 year olds (p=0.010). Salivary LB was associated with stimulated
      saliva's secretion rate only in 12 year olds (p=0.027). Salivary cariogenic
      microflora level and buffer capacity were associated in 6 year olds (p for
      MS=0.010; p for LB=0.052). Same association was observed only between salivary MS
      and buffer capacity in 12 year olds (p=0.081). Stimulated saliva's secretion rate
      and buffer capacity were associated only in 12 year olds (p=0.004). CONCLUSIONS:
      Information of caries risk factors should be used to work effectively on caries
      reduction in 6 year olds and 12 year olds in Riga.

PMID- 18708742
TI  - Regulation of Kv4.3 closed state inactivation and recovery by extracellular
      potassium and intracellular KChIP2b.
AB  - Mechanisms underlying Kv4 channel inactivation and recovery are presently
      unclear, although there is general consensus that the basic characteristics of
      these processes are not consistent with Shaker (Kv1) N- and P/C-type mechanisms.
      Kv4 channels also differ from Shaker in that they can undergo significant
      inactivation from pre-activated closed-states (closed-state inactivation, CSI),
      and that inactivation and recovery kinetics can be regulated by intracellular
      KChIP2 isoforms. To gain insight into the mechanisms regulating Kv4.3 CSI and
      recovery, we have analyzed the effects of increasing [K(+)](o) from 2 mM to 98 mM
      in the absence and in the presence of KChIP2b, the major KChIP2 isoform expressed
      in the mammalian ventricle. In the absence of KChIP2b, high [K(+)](o) promoted
      Kv4.3 inactivated closed-states and significantly slowed the kinetics of recovery
      from both macroscopic and closed-state inactivation. Coexpression of KChIP2b in 2
      mM [K(+)](o) promoted non-inactivated closed-states and accelerated the kinetics
      of recovery from both macroscopic and CSI. In high [K(+)](o), KChIP2b eliminated
      or significantly reduced the slowing effects on recovery. Attenuation of CSI by
      the S4 charge-deletion mutant R302A, which produced significant stabilization of
      non-inactivated closed-states, effectively eliminated the opposing effects of
      high [K(+)](o) and KChIP2b on macroscopic recovery kinetics, confirming that
      these results were due to alterations of CSI. Elevated [K(+)](o) therefore slows
      Kv4.3 recovery by stabilizing inactivated closed-states, while KChIP2b
      accelerates recovery by destabilizing inactivated closed-states. Our results
      challenge underlying assumptions of presently popular Kv4 gating models and
      suggest that Kv4.3 possesses novel allosteric mechanisms, which are absent in
      Shaker, for coupling interactions between intracellular KChIP2b binding motifs
      and extracellular K(+)-sensitive regulatory sites.

PMID- 18708743
TI  - Kv11.1 (ERG1) K+ channels localize in cholesterol and sphingolipid enriched
      membranes and are modulated by membrane cholesterol.
AB  - The localization of ion channels to specific membrane microdomains can impact the
      functional properties of channels and their role in cellular physiology. We
      determined the membrane localization of human Kv11.1 (hERG1) alpha-subunit
      protein, which underlies the rapidly activating, delayed rectifier K(+) current
      (I(Kr)) in the heart. Immunocytochemistry and membrane fractionation using
      discontinuous sucrose density gradients of adult canine ventricular tissue showed
      that Kv11.1 channel protein localized to both the cell surface and T-tubular
      sarcolemma. Furthermore, density gradient membrane fractionation using detergent
      (Triton X-100) and non-detergent (OptiPrep) methods from canine ventricular
      myocytes or HEK293 cells demonstrated that Kv11.1 protein, along with MiRP1 and
      Kv7.1 (KCNQ1) proteins, localize in cholesterol and sphingolipid enriched
      membrane fractions. In HEK293 cells, Kv11.1 channels, but not long QT-associated
      mutant G601S-Kv11.1 channels, also localized to cholesterol and sphingolipid
      enriched membrane fractions. Depletion of membrane cholesterol from HEK293 cells
      expressing Kv11.1 channels using methyl-beta-cyclodextrin (MbetaCD) caused a
      positive shift of the voltage dependence of activation and an acceleration of
      deactivation kinetics of Kv11.1 current (I(Kv11.1)). Cholesterol loading of
      HEK293 cells reduced the steep voltage dependence of I(Kv11.1) activation and
      accelerated the inactivation kinetics of I(Kv11.1). Incubation of neonatal mouse
      myocytes in MbetaCD also accelerated the deactivation kinetics of I(Kr). We
      conclude that Kv11.1 protein localizes in cholesterol and sphingolipid enriched
      membranes and that membrane cholesterol can modulate I(Kv11.1) and I(Kr).

PMID- 18708744
TI  - A novel LQT-3 mutation disrupts an inactivation gate complex with distinct rate
      dependent phenotypic consequences.
AB  - Inherited mutations of SCN5A, the gene that encodes Na(V)1.5, the alpha subunit
      of the principle voltage-gated Na(+) channel in the heart, cause congenital Long
      QT Syndrome variant 3 (LQT-3) by perturbation of channel inactivation. LQT-3
      mutations induce small, but aberrant, inward current that prolongs the
      ventricular action potential and subjects mutation carriers to arrhythmia risk
      dictated in part by the biophysical consequences of the mutations. Most
      previously investigated LQT-3 mutations are associated with increased arrhythmia
      risk during rest or sleep. Here we report a novel LQT-3 mutation discovered in a
      pediatric proband diagnosed with LQTS but who experienced cardiac events during
      periods of mild exercise as well as rest. The mutation, which changes a single
      amino acid (S1904L) in the Na(V)1.5 carboxy terminal domain, disrupts the channel
      inactivation gate complex and promotes late Na(+) channel currents, not by
      promoting a bursting mode of gating, but by increasing the propensity of the
      channel to reopen during prolonged depolarization. Incorporating a modified
      version of the Markov model of the Na(V)1.5 channel into a mathematical model of
      the human ventricular action potential predicts that the biophysical consequences
      of the S1904L mutation result in action potential prolongation that is seen for
      all heart rates but, in contrast to other previously-investigated LQT-3 mutant
      channels, is most pronounced at fast rates resulting in a drastic reduction in
      the cells ability to adapt APD to heart rate.

PMID- 18708746
TI  - Structural determinants for alpha-neurotoxin sensitivity in muscle nAChR and
      their implications for the gating mechanism.
AB  - Neurotoxins from snake venoms act as potent antagonists on the nicotinic
      acetylcholine receptors (nAChRs). Alpha-neurotoxins such as alpha-bungarotoxin
      (alpha-Btx) selectively bind to the skeletal muscle nAChRs among other subtypes,
      causing failure of the neuromuscular transmission. Through evolution, some
      species including snakes and mongoose have developed resistance to alpha
      neurotoxins via specific amino acid substitutions in their muscle-type nAChR
      alpha1 subunit, which constitutes most of the toxin-binding site. Here we analyze
      these sequence variations in the context of our recent crystal structure of the
      extracellular domain of the mouse nAChR alpha1 bound to alpha-Btx. Our structure
      suggests that alpha-Btx has evolved as an extremely potent antagonist of muscle
      nAChR by binding the receptor tightly, blocking its ligand site, and locking its
      conformation in a closed state. Conversely, most toxin-resistant mutations occur
      at the alpha-Btx binding interface on nAChR alpha1 but away from the agonist
      binding site. These mutations can interfere with the binding of alpha-Btx without
      having deleterious effect on the gating function. These analyses not only help
      understand the structural determinants for neurotoxin sensitivity in muscle-type
      nAChR, but also shed light on its gating mechanism.

PMID- 18708745
TI  - Modulation of neuronal voltage-activated calcium and sodium channels by
      polyamines and pH.
AB  - The endogenous polyamines spermine, spermidine and putrescine are present at high
      concentrations inside neurons and can be released into the extracellular space
      where they have been shown to modulate ion channels. Here, we have examined
      polyamine modulation of voltage-activated Ca(2+) channels (VACCs) and voltage
      activated Na(+) channels (VANCs) in rat superior cervical ganglion neurons using
      whole-cell voltage-clamp at physiological divalent concentrations. Polyamines
      inhibited VACCs in a concentration-dependent manner with IC(50)s for spermine,
      spermidine, and putrescine of 4.7 +/- 0.7, 11.2 +/- 1.4 and 90 +/- 36 mM,
      respectively. Polyamines caused inhibition by shifting the VACC half-activation
      voltage (V(0.5)) to depolarized potentials and by reducing total VACC
      permeability. The shift was described by Gouy-Chapman-Stern theory with a surface
      charge density of 0.120 +/- 0.005 e(-) nm(-2) and a surface potential of -19 mV.
      Attenuation of spermidine and spermine inhibition of VACC at decreased pH was
      explained by H(+) titration of surface charge. Polyamine-mediated effects also
      decreased at elevated pH due to the inhibitors having lower valence and being
      less effective at screening surface charge. Polyamines affected VANC currents
      indirectly by reducing TTX inhibition of VANCs at high pH. This may reflect
      surface charge induced decreases in the local TTX concentration or polyamine-TTX
      interactions. In conclusion, polyamines inhibit neuronal VACCs via complex
      interactions with extracellular H(+) and Ca. Many of the observed effects can be
      explained by a model incorporating polyamine binding, H(+) binding and surface
      charge screening.

PMID- 18708747
TI  - Ligand-based virtual screening to identify new T-type calcium channel blockers.
AB  - T-type calcium channels are involved in the generation of rhythmical firing
      patterns in the mammalian central nervous system and in various pathological
      alterations of neuronal excitability such as in epilepsy or neuropathic pain. In
      the search for new T-type calcium channel blockers that would help to treat these
      disorders, we have followed a bi-dimensional pharmacophore-based virtual
      screening approach to identify new inhibitors. Nineteen molecules extracted from
      AurSCOPE Ion Channels knowledgebase were used as query molecules to screen an
      external database. This in silico approach was then validated using
      electrophysiology. Interestingly, 16 compounds out of 38 distinct molecules
      tested showed more than 50% blockade of the Ca(V)3.2 mediated T-type current. Two
      series of compounds show chemical originality compared with known T-type calcium
      channel blockers.

PMID- 18708748
TI  - Assessing the chemical and biological diversity of an ion channels knowledge
      database.
AB  - The aim of the present work is to assess the chemical and biological diversity of
      ligands reported in scientific articles or patents to be active against ion
      channels targets. A specific query of the AurSCOPE Ion Channel knowledge database
      was constructed to retrieve a set of the most active non-peptide ligands tested
      in binding or electrophysiology experiments against all ion channel families. A
      biological activity threshold cutoff expressed by K(i), IC(50), or EC(50) was set
      to 300 nM. This activity cutoff was selected such that we would retrieve a set of
      compounds, which contain the most active ligands for all target families, but is
      a reasonable number to analyze. To encode the chemical space for the entire
      active dataset (9897 molecules), ChemAxon's chemical fingerprints were computed
      and optimized and then employed to cluster the dataset at a variety of different
      similarity thresholds. Concurrently, the exploration of the biological space was
      performed by associating with each chemical cluster the corresponding target or
      target family. Tri-dimensional visualization of different voltage- and ligand
      gated ion channel families projected into the active chemical space was obtained
      after a principal components analysis performed using selected molecular
      descriptors. The findings presented herein give a global picture of the realm of
      ion channels active ligands and link the knowledge on chemical structures with
      their respective biological activities.

PMID- 18708749
TI  - Alternative splicing matters: N-type calcium channels in nociceptors.
AB  - How many different calcium channels does it take to make a nervous system? The
      answer: more than any of us predicted. In 1975 Hagiwara and colleagues published
      the first evidence that functionally different calcium channels are expressed in
      cells. By 1999, the calcium channel family could boast ten members, each member
      defined by a unique set of attributes to support their cellular functions and by
      unique amino acid sequences. Although nine of these genes are expressed in the
      nervous system, that number still seemed insufficient to support the wide
      spectrum of neuronal functions controlled by voltage-gated calcium channels. This
      discrepancy is probably explained by alternative pre-messenger RNA splicing which
      substantially expands the number of protein activities available from a limited
      number of genes. Like many other ion channel genes, each Ca(V)alpha(1) gene has
      the capacity to generate perhaps thousands of unique splice isoforms with unique
      functional properties. The high level of conservation among alternatively spliced
      exons in Ca(V)2.2 genes of different species and in some cases closely related
      genes implies biological importance. A number of Ca(V)alpha(1) isoforms have been
      identified from neural tissue but until recently we lacked direct evidence
      linking a specific splice site in a calcium channel gene to a specific function
      in an identified neuron population. Our recent studies show that alternative pre
      mRNA splicing of a pair of 32 amino acid encoding exons in the C-terminus of
      Ca(V)2.2, e37a and e37b, underlie the expression of two mutually exclusive N-type
      channel isoforms. The inclusion of e37a creates a module that couples the N-type
      channel to a powerful form of G protein-dependent inhibition. The inhibitory
      pathway that works through e37a is voltage-independent, requires G(i/o) and
      tyrosine kinase activation, and is used by mu opioid and GABA(B) receptors to
      downregulate N-type channel activity. Combined with our previous studies that
      show enrichment of e37a in nociceptors, our data suggest a molecular basis for
      the high susceptibility of N-type currents in sensory neurons to voltage
      independent inhibition following G protein activation.

PMID- 18708750
TI  - Regulation of KATP channel expression and activity by the SUR1 nucleotide binding
      fold 1.
AB  - ATP-sensitive K(+) (K(ATP)) channels are oligomeric complexes of pore-forming
      Kir6 subunits and regulatory Sulfonylurea Receptor (SUR) subunits. SUR, an ATP
      Binding Cassette (ABC) transporter, confers Mg-nucleotide stimulation to the
      channel via nucleotide interactions with its two cytoplasmic domains (Nucleotide
      Binding Folds 1 and 2; NBF1 and NBF2). Regulation of K(ATP) channel expression is
      a complex process involving subunit assembly in the ER, SUR glycosylation in the
      Golgi, and trafficking to the plasma membrane. Dysregulation can occur at
      different steps of the pathway, as revealed by disease-causing mutations. Here,
      we have addressed the role of SUR1 NBF1 in gating and expression of reconstituted
      channels. Deletion of NBF1 severely impairs channel expression and abolishes
      MgADP stimulation. Total SUR1 protein levels are decreased, suggestive of
      increased protein degradation, but they are not rescued by treatment with
      sulfonylureas or the proteasomal inhibitor MG-132. Similar effects of NBF1
      deletion are observed in recombinant K(ATP) channels obtained by "splitting" SUR1
      into two separate polypeptides (a N-terminal "half" and a C-terminal "half").
      Interestingly, the location of the "splitting point" in the vicinity of NBF1 has
      marked effects on the MgADP stimulation of resulting channels. Finally, ablation
      of the ER retention motif upstream of NBF1 (in either "split" or full-length
      SUR1) does not rescue expression of channels lacking NBF1. These results indicate
      that, in addition to NBF1 being required for MgADP stimulation of the channel, it
      plays an important role in the regulation of channel expression that is
      independent of the ER retention checkpoint and the proteasomal degradation
      pathway.

PMID- 18708751
TI  - Regulation of T-type calcium channels in the peripheral pain pathway.
AB  - Recent evidence strongly suggests that both central and peripheral T-type Ca(2+)
      channels enhance somatic and visceral nociceptive inputs, as well as that
      regulation of T-type Ca(2+) channel function can result in significant changes of
      pain threshold in a variety of animal models. Therefore, T-type Ca(2+) channels
      in peripheral and central pain pathways, although previously unrecognized, may
      have great importance as targets for developing new therapies against pain. This
      is particularly critical in cases in which currently available treatments are
      limited due to serious side effects or are not consistently effective (e.g.,
      chronic neuropathic pain). In this review, we summarize recent studies of the
      regulation of T-type channels in peripheral sensory neurons by means of redox
      agents and neuroactive steroids, as well as studies of the function of these
      channels in the pathophysiology of neuropathic pain.

PMID- 18708752
TI  - Ultraconserved elements: genomics, function and disease.
AB  - Evolutionary conservation has become a powerful tool to identify functionally
      important genomic sequences/elements in the human genome. There are 481 genomic
      segments longer than 200 base pairs (bp) that are absolutely conserved (100%
      identity with no insertions or deletions) between human, mouse and rat genomes.
      Such segments are known as ultraconserved elements (UCEs). Although our knowledge
      of UCEs is limited, most recent studies suggest that UCEs play a functional role
      in vertebrate genomes, such as serving as long-range enhancers of flanking genes,
      regulating splicing and epigenetic modifications, and functioning as
      transcriptional coactivator. Most recent studies show that expression of UCEs is
      consistently altered in tumors, strongly suggesting these elements may also be
      involved in human disease such as cancer development.

PMID- 18708753
TI  - Effects of 4E-BP1 expression on hypoxic cell cycle inhibition and tumor cell
      proliferation and survival.
AB  - Elevated activity of the eIF4F complex, which controls initiation of cap
      dependent mRNA translation, has been linked to cancer progression. eIF4E
      recruitment to eIF4F is the rate limiting step of complex assembly and is
      regulated by eIF4E-Binding Proteins (4E-BPs). When stimulated, the mammalian
      Target of Rapamycin complex 1 (mTORC1) phosphorylates 4E-BP1, which then releases
      eIF4E. Hypoxia inhibits mTORC1 activity and therefore cap-dependent protein
      synthesis. To establish a novel genetic test of the role of eIF4F activity in
      regulating cell division and viability within hypoxic tumor microenvironments, we
      generated shRNA mediated 4E-BP1 knock-down in Rh30 rhabdomyosarcoma cells. 4E-BP1
      knock-down relieved hypoxia-mediated inhibition of cycle progression in vitro and
      was correlated with increased expression of cyclin D1 and c-Myc. Xenograft tumors
      derived from these cells also displayed enhanced expression of cyclin D1 and c
      Myc along with antiapoptotic genes encoding Bcl-x(L), and XIAP, and failed to
      develop the extensive necrotic zones and edema observed in control tumors.
      Surprisingly, 4E-BP1 knock-down also leads to a dramatic increase in aberrant
      mitoses in vivo and enhanced expression of Mad2 and securin. Thus, reduced
      expression of the negative regulator of eIF4E has significant effects on tumor
      development, and is associated with enhanced cell proliferation and survival.

PMID- 18708754
TI  - Everolimus (RAD001) and anti-angiogenic cyclophosphamide show long-term control
      of gastric cancer growth in vivo.
AB  - Metronomic dosing of cytotoxic drugs such as cyclophosphamide has shown anti
      angiogenic activity, most likely by inducing hypoxia in tumors. Hypoxia leads to
      activation of escape mechanisms allowing tumor cell survival. This potentially
      limits the activity of anti-angiogenic strategies. We hypothesized that mTORC1
      inhibition by everolimus (RAD001) leads to suppression of HIF-1alpha and VEGF
      resulting in synergistic anti-tumor activity in combination with anti
      angiogenically dosed cyclophosphamide. In vitro, effects of everolimus on mTORC1
      signaling, proliferation, cell cycle, HIF-1alpha expression and VEGF secretion
      were evaluated in two gastric cancer cell lines. In vivo, anti-tumor activity of
      everolimus in combination with metronomic cyclophosphamide was studied in a NCI
      N87 human gastric cancer SCID mouse xenograft model. Expression of Ki-67 and HIF
      1alpha, activated caspase 3, microvascular density (MVD) and tumor necrotic area
      assessed. Everolimus decreased proliferation and attenuated production of HIF
      1alpha as well as VEGF in gastric cancer cells in vitro. In vivo, everolimus
      significantly inhibited tumor growth. This anti-tumor activity was linked to a
      significant increase in tumor necrotic area (p < 0.02) and trends for decreased
      proliferation, increased apoptosis, decreased HIF-1alpha and lower tumor MVD (p =
      n.s.). The combination of everolimus and cyclophosphamide resulted in a striking
      and highly significant long-term tumor growth control compared to monotherapy (p
      < 0.001), which was associated with a sharp increase in central tumor necrosis (p
      < 0.001). In conclusion, the combination of everolimus and metronomic
      cyclophosphamide showed synergistic anti-tumor activity. Depriving cancer cells
      by everolimus of factors necessary for their survival under hypoxia induced by
      anti-angiogenic chemotherapy appears to be a promising approach for treatment of
      gastric cancer.

PMID- 18708755
TI  - c-Myb oncoprotein is an essential target of the dleu2 tumor suppressor microRNA
      cluster.
AB  - The dleu2 tumor suppressor locus encodes two microRNAs, miR-15a and miR-16, which
      are thought to play an important role in B-cell neoplasms. However, relatively
      little is known about proteins that regulate or are regulated by this microRNA
      cluster. Here we demonstrate that the Pax5 oncoprotein downregulates the dleu2
      gene and at the same time boosts expression of its own heterodimeric partner c
      Myb. Interestingly, c-Myb upregulation occurs primarily at a post-transcriptional
      level, suggesting that it might be a target for microRNAs such as miR-15a/16.
      Indeed, miR-15a/16 have predicted binding sites in the c-Myb 3'-UTR and through
      them diminish protein output in luciferase sensor assays. Moreover, forced
      overexpression of miR-15a/16 reduces endogenous c-Myb levels and compromises Pax5
      function. Conversely, restoration of c-Myb levels partly alleviates tumors
      suppressive effects of miR-15a/16, suggesting that c-Myb is a key downstream
      target of this microRNA cluster.

PMID- 18708756
TI  - Players in human liposarcoma: JUN joins the cast.

PMID- 18708758
TI  - siRNA-mediated inhibition of hTERT enhances chemosensitivity of hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide.
      However, there is no effective treatment for HCC. It has been shown that
      sustained activation of telomerase is essential for the growth and progression of
      HCC, suggesting that telomerase is a rational target for HCC therapy. Here, we
      investigated the effects of siRNA-mediated knockdown of hTERT, the catalytic and
      rate-limiting subunit of telomerase, on the sensitivity of HCC cells to
      cisplatin. While silencing of hTERT and the resultant inhibition of telomerase
      activity by infection with the recombinant adenovirus expressing a hTERT siRNA
      (Ad-si/hTERT) alone did not affect the proliferation and viability of SMMC7721
      and HepG2 HCC cells within five days, co-administration of Ad-si/hTERT, but not
      the empty adenovirus vector, with cisplatin caused much greater extent of
      apoptosis in vitro under the same conditions and induced significantly more
      robust inhibition of SMMC7721 and HepG2 tumors growth in a mouse tumor xenograft
      model than cisplatin monotherapy. Our results demonstrated the synergistic effect
      between hTERT siRNA and cisplatin in the suppression of HCC progression and
      indicated that the combination of hTERT-specific siRNA and cisplatin could be an
      effective therapy for HCC.

PMID- 18708757
TI  - Searching for a cure: gene therapy for glioblastoma.
AB  - Glioblastoma multiforme (GBM) is an invariably fatal malignancy. The lethality of
      GBM has been linked to the highly invasive nature of GBM cells, their escape from
      immune cell oversight and their high degree of resistance to multiple established
      therapeutic modalities. The resistance of GBM cells to undergo death processes
      has, in part, been associated with mutations of specific oncogenes and altered
      expression of other signaling molecules that lead to reduced capacities to
      activate multiple apoptosis pathways as well as altered rates of DNA repair and
      autophagy in response to cytotoxic drugs and cellular stresses. This review will
      examine how gene therapeutic approaches have been used in the past and are
      continuing to be used alongside cell signaling modulators and DNA damaging agents
      as clinical tools to treat GBM. The concerted use of established and novel signal
      transduction modulatory agents on GBM survival may have potential to lower the
      apoptotic threshold and facilitate killing in this lethal malignancy.

PMID- 18708759
TI  - Granulocyte activity in patients with cancer and healthy subjects.
AB  - In our study, we investigated the intracellular killing ability of granulocytes
      for healthy and ill subjects by measuring NADH oxidase activity and release of
      hydrogen peroxide. The protocol methodology measured the hydrogen peroxide
      released after granulocytes activation by PMA (phorbol 12-myristate 13-acetate)
      by using the Amplex Red assay, which included counting granulocytes by flow
      cytometer and measurement of the kinetic curve of NADPH oxidase activity by
      fluorometer. Two parameters were used to describe the level of granulocyte
      activity: the initial rate of NADPH-oxidase enzyme activity and the level of
      hydrogen peroxide released after 20 min of granulocyte activation. The method was
      applied to measure granulocyte activity in 55 healthy subjects and 30 patients
      with cancer. It was demonstrated that applied procedure is sensitive for
      estimation of the disease activity. The granulocyte activity in patients with
      cancer was compared with the granulocyte activity of healthy subjects and
      demonstrated the downregulation of NADPH oxidase activity. We showed that
      granulocytes of cancer patients had inhibited oxidative burst and less NADPH
      oxidase activity.

PMID- 18708760
TI  - Harpooning the Cvt complex to the phagophore assembly site.
AB  - Autophagy is a catabolic process employed by eukaryotes to degrade and recycle
      intracellular components. When this pathway is induced by starvation conditions,
      part of the cytoplasm and organelles are sequestered into double-membrane
      vesicles called autophagosomes, and delivered into the lysosome/vacuole for
      degradation. In addition to the random bulk elimination of cytoplasmic contents,
      the selective removal of specific cargo molecules has also been described. These
      selective types of autophagy are characterized by the recruitment of the cargo
      destined for degradation in close proximity to the forming double-membrane
      vesicle that results in an exclusive incorporation (that is, without bulk
      cytoplasm). A number of factors required for selective types of autophagy have
      been identified. In particular, we have recently shown that actin and the actin
      binding Arp2/3 protein complex are involved in the cytoplasm to vacuole targeting
      (Cvt) pathway, a yeast selective type of autophagy. The contribution at a
      molecular level of these factors, however, remains unknown. In this addendum, we
      present mechanistic models that take into account possible roles of actin and the
      Arp2/3 complex in the Cvt pathway.

PMID- 18708761
TI  - Hypoxia-inducible proto-oncogene Pim-1 is a prognostic marker in pancreatic
      ductal adenocarcinoma.
AB  - BACKGROUND: Pim-1 is a proto-oncogene involved in cell survival, differentiation
      and proliferation in several hematologic and epithelial malignancies. Clinically,
      absence of Pim-1 expression correlates with poor prognosis in prostate cancer. In
      the present study, the expression of Pim-1 is analyzed in pancreatic cancer and
      correlated to clinicopathological parameters. RESULTS: Compared to benign,
      inflammatory and pre-malignant conditions (i.e., the normal pancreas, chronic
      pancreatitis and benign intraductal papillary mucinous neoplasm), expression of
      Pim-1 mRNA and protein increased significantly in pancreatic malignancies.
      Absence of Pim-1 immunopositivity in cancer cells strongly correlated with a poor
      prognosis (median survival 13.8 vs. 23.4 months, p = 0.0016). In vitro, rapidly
      dividing (high versus low serum concentrations) and hypoxic cells displayed
      higher Pim-1 mRNA and protein levels. METHODS: Pim-1 mRNA and protein was
      evaluated with quantitative real-time RT-PCR, immunofluorescence and
      immunocytochemistry analyses. Ex vivo expression analysis using semi-quantitative
      immunohistochemistry was performed using human pancreatic tissues of the normal
      pancreas (n = 10), chronic pancreatitis (n = 30), pancreatic ductal
      adenocarcinoma (n = 59) and other pancreatic tumors (n = 42). In consecutive
      sections HIF1-alpha was used as a marker of hypoxia. Survival of patients (n =
      35) was compared using the Kaplan-Meier method and a log-rank test. In vitro
      analyses were performed using cultured pancreatic cancer cell lines (n = 8) and
      primary human pancreatic stellate cells. CONCLUSION: Hypoxia is a novel inducer
      of Pim-1 expression. Compared to non-malignant tissues Pim-1 significantly
      increases in pancreatic cancer. However, the presence of Pim-1 in cancer cells
      has a positive prognostic impact.

PMID- 18708762
TI  - Preparation and testing of bevacizumab radioimmunoconjugates with Bismuth-213 and
      Bismuth-205/Bismuth-206.
AB  - Bevacizumab, a humanized anti-VEGF monoclonal antibody has shown promise in
      various clinical trials. We report the development and testing of Bi-213 (an
      alpha-emitting radionuclide) labeled bevacizumab for in vitro and in vivo studies
      using two different chelators viz cDTPA and CHX-A''. The developed labeling
      method showed high labeling yields of 93.6% and 89.7% for cDTPA and CHX-A''
      respectively and the results were reproducible. The in vitro and in vivo
      stability tests were carried out using Bi-213 and long half-life Bismuth isotope
      (Bi-205/Bi-206) for pharmacokinetics. The in vitro results showed remarkable
      stability of the radiolabeled bevacizumab regardless of the chelator. The in vivo
      pharmacokinetics studies however, showed that the uptake and retention of cDTPA
      bevacizumab was significantly higher in kidneys (p-value 0.02) and lower in liver
      and spleen (p-value <0.0001 and 0.0009 respectively). The values for the two
      conjugates compared well in blood but the longer term data for CHX-A'' conjugate
      showed slow clearance resulting in a significantly longer blood half-life of the
      product (211 hours compared to 4 hours for cDTPA-bevacizumab). Preliminary in
      vivo results showed increased efficacy of the combination therapy compared to
      bevacizumab only. The tumor area (mm(2)) decreased from 24.8 +/- 3.6 and 12.8 +/-
      1.7 for 1 and 3 mg/kg cold bevacizumab only to 6.5 +/- 0.7 and 7.5 +/- 4.8 when
      single dose of 333 MBq/kg of (213)Bi-bevacizumab was administered as combination
      therapy. In conclusion it can be said that stable radiolabeled bevacizumab
      conjugates can be prepared with Bi-213 with either chelators used. The shorter
      blood half-life with cDTPA-bevacizumab may not be a major concern with Bi-213 as
      its own half-life is 46 minutes only. The combination therapy proved superior to
      bevacizumab alone therapy, a phenomenon that can be particularly useful in
      cancers where bevacizumab alone has shown limited success like prostate cancer.

PMID- 18708763
TI  - p38 and cancer: Yang gets Yin.

PMID- 18708764
TI  - Apoptin induces apoptosis in an oral cancer mouse model.
AB  - Apoptin, a chicken anemia virus-derived protein, induces apoptosis in various
      tumor cell lines and xenografted tumors. Its apoptotic activity is not hampered
      by tumor-suppressor p53 mutations or overexpression of anti-apoptosis proteins
      Bcl-2 or Bcl-x(L). We report for the first time the effects of apoptin expression
      in primary oral tumors, induced by the carcinogen 4-Nitroquinoline- 1-oxide in
      immunocompetent mice. In vivo a significant amount of primary oral tumor cells
      expressing apoptin cells underwent apoptosis, whereas synthesis of the LacZ
      control product did not. Ectopical expression of apoptin in passage 1 cell
      cultures derived from these oral tumors also resulted in apoptin-induced. Both in
      vivo and in-vitro treated cells underwent apoptosis via the activation of caspase
      3. The fact that apoptin induces apoptosis in primary squamous cell carcinoma
      cells indicates that apoptin is a potential therapeutic agent for treatment of
      head and neck squamous cell carcinoma.

PMID- 18708765
TI  - alpha-synuclein degradation by autophagic pathways: a potential key to
      Parkinson's disease pathogenesis.
AB  - The neuronal protein alpha-synuclein is thought to be central in the pathogenesis
      of Parkinson's disease (PD). Excessive wild type alpha-synuclein levels can lead
      to PD in select familial cases and alpha-synuclein protein accumulation occurs in
      sporadic PD. Therefore, elucidation of the mechanisms that control alpha
      synuclein levels is critical for PD pathogenesis and potential therapeutics. The
      subject of alpha-synuclein degradation has been controversial. Previous work
      shows that, in an assay with isolated liver lysosomes, purified wild type alpha
      synuclein is degraded by the process of chaperone-mediated autophagy (CMA).
      Whether this actually occurs in a cellular context has been unclear. In our most
      recent work, we find that wild type alpha-synuclein, but not the closely related
      protein beta-synuclein, is indeed degraded by CMA in neuronal cells, including
      primary postnatal ventral midbrain neurons. Macroautophagy, but not the
      proteasome, also contributes to alpha-synuclein degradation. Therefore, two
      separate lysosomal pathways, CMA and macroautophagy, degrade wild type alpha
      synuclein in neuronal cells. It is hypothesized that impairment of either of
      these two pathways, or of more general lysosomal function, may be an initiating
      factor in alpha-synuclein accumulation and sporadic PD pathogenesis.

PMID- 18708766
TI  - Aurora A, Aurora B and survivin are novel targets of transcriptional regulation
      by histone deacetylase inhibitors in non-small cell lung cancer.
AB  - BACKGROUND: Analysis of biopsies from a recent clinical trial suggested that
      Depsipeptide FK228 (DP) inhibits Aurora kinase expression in lung cancer cells.
      The present study was undertaken to confirm and extend these observations.
      RESULTS: Aurora A and B mRNA levels in lung cancer cells were considerably higher
      than levels in normal pulmonary epithelia. DP, TSA and SAHA inhibited Aurora A,
      Aurora B and survivin expression with kinetics that were remarkably similar
      within individual cell lines, and appeared to coincide with p53 expression
      status. These effects were not observed following treatment with geldanamycins.
      Inhibition of Aurora B transcription coincided with decreased H3K9Ac and H3K4Me2
      activation marks, and accumulation of H3K9Me3, as well as MBD1, MBD2 and MBD3
      repression marks within the minimal Aurora B promoter. Knockdown of MBD1, -2 or 
      3 did not reproducibly abrogate inhibition of Aurora or survivin expression by DP
      or TSA. DP and TSA decreased expression and altered localization of Aurora
      kinases and survivin, resulting in mitotic catastrophe in lung cancer cells.
      METHODS: Aurora A, and Aurora B levels in lung cancer cells and normal
      respiratory epithelia were assessed using quantitative RT-PCR techniques. These
      methods, as well as as Western blots were used to examine expression of Auroras
      A/B, and several related genes/proteins in lung cancer cells exposed to DP, TSA,
      SAHA and geldanamycins. Transient transfection promoter-reporter assays, and
      chromatin immunoprecipitation (ChIP) techniques were used to examine DP-mediated
      changes in activity and chromatin structure of the Aurora B promoter. Confocal
      imaging techniques were used to examine the effects of DP and TSA on mitotic
      progression in lung cancer cells. CONCLUSIONS: Novel transcriptional regulatory
      mechanisms involving Aurora kinase and survivin appear to contribute to
      cytotoxicity mediated by HDAC inhibitors in lung cancer cells.

PMID- 18708823
TI  - Therapeutic angiogenesis: a new treatment approach for ischemic heart disease-
      Part II.
AB  - Angiogenesis is the biologic process of forming new blood vessels and is being
      investigated as an innovative therapeutic approach to help manage ischemic heart
      disease and peripheral vascular disease. Research studies have identified various
      angiogenic growth factors and progenitor cells that can enhance new blood vessel
      formation. This is Part II of an article that began publication in the
      July/August issue of Cardiology in Review. Preclinical investigations in animal
      models have explored the potential use of growth factors with and without
      progenitor cells to treat myocardial ischemia. The results of clinical trials
      with growth factor infusions and gene therapy techniques to enhance growth factor
      production have shown some promise, but therapeutic angiogenesis remains at an
      early stage of development.

PMID- 18708824
TI  - Treatment of atrial fibrillation and atrial flutter: Part II.
AB  - Atrial fibrillation (AF) is often complicated by a life-threatening ventricular
      response, and emergency electrocardioversion and/or drug therapy to reduce the
      rapid ventricular rate may be necessary. However, patients with AF and Wolff
      Parkinson-White syndrome should not be given digoxin or calcium channel blockers.
      Elective direct current (DC) cardioversion has a higher success rate and a lower
      incidence of cardiac adverse effects than does medical cardioversion in
      converting AF to sinus rhythm. Unless transesophageal echocardiography has shown
      no thrombus in the left atrial appendage before cardioversion, oral warfarin
      should be given for 3 weeks before elective direct current or drug cardioversion
      of AF and continued for at least 4 weeks after maintenance of sinus rhythm. Many
      cardiologists prefer, especially in older patients, ventricular rate control plus
      warfarin rather than maintaining sinus rhythm with antiarrhythmic drugs. Patients
      with chronic or paroxysmal AF at high risk for stroke should be treated with long
      term warfarin to achieve an international normalized ratio of 2.0-3.0. Patients
      with AF at low risk for stroke or with contraindications to warfarin should be
      treated with aspirin 325 mg daily. Management of atrial flutter is similar to
      management of AF.

PMID- 18708825
TI  - Natriuretic peptide testing in clinical medicine.
AB  - Since the discovery of atrial natriuretic factor in 1981 by de Bold et al, there
      has been tremendous progress in our understanding of natriuretic peptides (NPs).
      Recently, testing for brain-type NP (BNP) and its amino terminal cleavage
      equivalent (NT-proBNP) has been rapidly adopted in clinical medicine for numerous
      indications, including the diagnosis and exclusion of heart failure (HF). In this
      regard, logical application of BNP or NT-proBNP testing may not only reduce
      healthcare costs but also potentially reduce adverse clinical outcomes. With
      respect to this fact, the potential importance of the concentration of the NPs
      for prognosis and the response of BNP or NT-proBNP to therapeutic intervention in
      terms of clinical events has been demonstrated. On the basis of these
      observations it is reasonable to expect that concentrations of these peptides
      might be useful for the management of patients with HF, acting as a gauge of
      therapeutic accuracy and/or stability of disease. Besides HF, the prognostic
      utility of NPs has been explored in other settings, particularly in ischemic
      heart disease and those conditions that lead to right ventricular dysfunction.

PMID- 18708826
TI  - Investigational antiplatelet drugs for the treatment and prevention of coronary
      artery disease.
AB  - Antiplatelet therapy for the prevention and treatment of coronary artery disease
      (CAD) has undergone dramatic changes and improvements. Aspirin remains the first
      line antiplatelet drug for clinical use. Newer platelet inhibitors such as the
      thienopyridine agents, ticlopidine and clopidogrel, have also been shown to be
      effective in treating CAD. There have been ongoing efforts to evaluate newer
      antiplatelet drugs, with the potential to improve clinical efficacy and safety.
      Some of the more promising antiplatelet agents include new adenosine diphosphate
      receptor antagonists such as prasugrel, cangrelor, and ticagrelor (AZD6140). In
      addition, a new thromboxane receptor antagonist, NCX-4016, a newly discovered
      protease-activated receptor antagonist that targets thrombin-induced platelet
      aggregation, and anti-von Willebrand factor aptamers show tremendous promise in
      refining antiplatelet therapy by targeting different receptors and molecules.

PMID- 18708827
TI  - Acute inferior wall myocardial infarction and percutaneous coronary intervention
      of the right coronary during active labor: a clinical report and review of the
      literature.
AB  - Acute myocardial infarction (AMI) is a rare event in women of childbearing age
      and has been estimated to occur at a rate of 1 in 10,000 women during pregnancy.
      First reported on in 1922, subsequent reports appeared in the literature
      indicating the unique features of this condition which can significantly affect
      both maternal and fetal outcomes. With the current maternal trend of childbearing
      at an older age, in addition to the effects of cigarette smoking, stress and
      cocaine use, the occurrence of AMI during pregnancy, albeit uncommon, can be
      expected to increase. In this article we describe a unique case of a 42-year-old
      woman with an acute inferior wall MI who underwent a percutaneous angioplasty and
      placement of a bare-metal stent during active labor. The patient tolerated the
      procedure well and underwent a successful cesarean section with delivery of
      twins. The subsequent discussion examines the clinical aspects of gestational and
      early postpartum AMI and reviews current strategies for both diagnosis and
      treatment.

PMID- 18708828
TI  - Metformin use in decompensated heart failure.
AB  - Metformin is associated with decreased mortality and morbidity in stable heart
      failure patients with diabetes mellitus type II. Diabetic heart failure patients
      with elevated systolic blood pressure are at increased risk for developing acute
      decompensated heart failure, which is often associated with decreased kidney
      function. Metformin-associated lactic acidosis is a rare but fatal side effect
      that may occur when kidney function is decreased. During acute decompensated
      heart failure, timely treatment may prevent the decrease in kidney function to
      the threshold associated with an increased risk of metformin-associated lactic
      acidosis. Metformin should not be withheld in diabetic patients with stable heart
      failure who do not have other risk factors for acute decompensated heart failure
      or lactic acidosis.

PMID- 18708829
TI  - An opportunity worth seizing.

PMID- 18708830
TI  - Feelings of living donors about adult-to-adult living donor liver
      transplantation.
AB  - This study investigated the feelings of living donors about adult-to-adult liver
      transplantation. We interviewed 18 donors about their feelings before and after
      transplantation using semistructured interviews and then conducted a content
      analysis of their responses. Before transplantation, many donors reported that
      they wanted recipients to live for the donor or his or her family, and there was
      no one else to donate. Many donors were not anxious, did not feel coerced, and
      did not consider donation dangerous. Some reported being excited at facing a new
      experience. Some said they would not mind whatever happens. Others were anxious
      or unsure about the operation. Diagnostic testing and preoperative blood banking
      were painful. Donors experienced increasing stress just before the operation.
      After transplantation, some donors verbalized feeling more grateful to others and
      that they gained maturity. Throughout the process, donors were concerned about
      their recipients. Our results suggest that donors might act for themselves or
      their family. It is important to recognize the varied responses of donors'
      feelings toward liver transplant recipients.

PMID- 18708831
TI  - Familial polyposis: a case study.
AB  - This article presents a case study of a patient who was treated for 5 years from
      the time of diagnosis until his death. The patient was diagnosed with familial
      polyposis at the age of 35 due to a family history of the same. He suffered from
      low body image and showed a poor response to treatment, especially regarding
      nutrition. The period of time related to the presentation of symptoms and the
      patient's subsequent deterioration was characterized by attempts on the part of
      nursing staff to improve the patient's quality of life. Treatment of multiple
      fistulae was employed, while keeping the skin intact, along with the creative
      development of a unique bandaging method. This article describes the course of
      the patient's disease and specifies his problems and their solutions. It is hoped
      that presentation of this case will benefit caregiving staff in dealing with
      similar cases.

PMID- 18708832
TI  - Supplemental oxygen during moderate sedation and the occurrence of clinically
      significant desaturation during endoscopic procedures.
AB  - Gastrointestinal endoscopy is the method of choice for the diagnosis and
      treatment of diseases of the esophagus, stomach, and colon. Moderate sedation is
      commonly used to sedate patients for endoscopic procedures. The objective of this
      study is to determine whether supplemental oxygen administered prior to and
      during moderate sedation decreases episodes of clinically significant oxygen
      desaturation in adults undergoing endoscopic procedures. Three hundred eighty
      nine subjects participated in the study. Of these, 194 patients were assigned to
      the experimental group and 195 patients to the control group. Use of supplemental
      oxygen was the study intervention. At baseline, the two groups did not differ
      significantly with respect to age, gender, body mass index, ethnicity, type of
      procedure, American Society of Anesthesiologists score, and pulse or respiratory
      rate. Of the control group, 70.8% (138/195) of patients experienced a
      desaturation episode compared with 12.4% (24/194) of experimental patients (p <
      .00001). Patients receiving supplemental oxygen were 98% less likely to
      experience desaturation than the controls. The results of this study support the
      routine use of supplemental oxygen (2 liters/minute) during endoscopic procedures
      to prevent desaturation. On the basis of the study data, it is recommended that
      patients undergoing endoscopy with moderate sedation, who meet the inclusion and
      exclusion criteria of this study, receive supplemental oxygen (2 L/min). Routine
      incorporation of this recommendation in hospital policies will ensure that
      patients routinely receive this preventive measure: supplemental oxygen during
      moderate sedation and the occurrence of clinically significant desaturation
      during endoscopic procedures.

PMID- 18708833
TI  - Novel 5-aminosalicylic acid formulations in ulcerative colitis: old dog, new
      tricks.
AB  - Ulcerative colitis is a chronic inflammatory bowel disease, often associated with
      abdominal pain, rectal bleeding, fatigue, and poor quality of life. Although 5
      aminosalicylic acid (5-ASA) preparations are the mainstay of treatment of this
      condition, the observed efficacy of many current formulations is limited by
      delivery systems that require multiple-daily dosing schedules and are associated
      with poor patient adherence. It is of critical importance that patients adhere to
      medication regimens, because failure to do so has been shown to result in a
      greater number of disease flares and an increased risk of complications,
      including colorectal cancer. Patient-friendly formulations of 5-ASA have recently
      been approved or are in development to overcome the limitations of many older
      formulations and improve remission rates. As a major point of contact for many
      patients with ulcerative colitis, it is essential that gastrointestinal nurses
      keep abreast of such relevant developments in treatment options. Indeed, nurses
      are a crucial educational conduit for patients and are in a unique position to
      serve as trusted educators on important issues. This review provides an update on
      recent advances in 5-ASA therapy to ensure that gastrointestinal nurses are aware
      of potential strategies for improving clinical outcomes of patients with
      ulcerative colitis.

PMID- 18708834
TI  - Thinking about changing your dress code.

PMID- 18708835
TI  - A pancreatic cancer survivor support group.

PMID- 18708836
TI  - Breaking the age barrier for liver transplantation.

PMID- 18708837
TI  - G-tubes and skin care, oh my!

PMID- 18708838
TI  - Radiation safety in the endoscopy setting. SGNA guideline.

PMID- 18708841
TI  - HIV and rehabilitation: development of a conceptual framework for curriculum
      planning.
AB  - The overall purpose of this paper is to present the development of a conceptual
      framework of existing HIV curricula and educational resources on to inform future
      curriculum planning for the education of rehabilitation professionals on
      rehabilitation in the context of HIV/AIDS. We conducted a scoping review of the
      literature from 1980 onwards to identify existing HIV curricula and resources
      used with current or future health professionals. Preliminary findings were
      reviewed with a national Advisory Committee and a framework was developed to
      inform future curriculum planning. The Conceptual Framework of Existing HIV
      Curricula for Health Professionals classified curricula based on whether it was
      interprofessional or uniprofessional, and targeted to rehabilitation
      professionals or more broadly included other health professionals. This framework
      consisted of four intersecting components that represented different types of
      curricula: (a) interprofessional HIV curricula specific to rehabilitation
      professionals, (b) uniprofessional HIV curricula specific to rehabilitation
      professionals, (c) interprofessional HIV curricula for health professionals, and
      (d) uniprofessional HIV curricula for health professionals. Evidence from the
      framework suggested that an interprofessional HIV curriculum designed for
      rehabilitation professionals may be an ideal model from which to build future HIV
      rehabilitation curricula. In summary, a range of HIV curricula exist that vary in
      the type of educational approach and the range of health professionals targeted.
      Future development, implementation, and evaluation of an interprofessional
      education curriculum will help to increase knowledge and capacity among current
      and future rehabilitation professionals so that they may better meet the needs of
      people living with HIV/AIDS in Canada.

PMID- 18708842
TI  - Eliminating toe-fixing pattern can improve standing and gait pattern of children
      with cerebral palsy in a qualitative way.
AB  - Toe-fixing pattern has been observed to be a compensatory strategy for children
      with cerebral palsy (CP) to gain body stability. It has been shown that
      application of toe sponges could eliminate the toe fixing, and thus would force
      the children with CP to use the potential resources of their impaired postural
      system. The aim of this study was to investigate the immediate regression and
      treatment effects of toe-sponges application on standing and walking patterns in
      children with CP. A controlled experimental study was conducted, involving 24
      school-aged children with CP who were ambulatory with or without walking aids.
      Twelve children in the experimental group wore toe sponges for 3 weeks whereas
      the other 12 children in the control group did not. The results did not show a
      significant difference indicating immediate regression after application of toe
      sponges in all children or a treatment effect in the experimental group after
      wearing the toe sponges for 3 weeks. Qualitative improvement of walking pattern
      in the experimental group was, however, observed. It was believed that the effect
      of toe-sponge application on improving the standing and walking patterns in
      children with CP was masked by the children shifting the compensation from toe
      flexion to the other body parts. Issues that need to be considered in the further
      studies were suggested.

PMID- 18708843
TI  - Measuring effect sizes using manifest versus latent variables: consequences and
      implications for research.
AB  - Reporting of effect sizes allows the description of mean differences
      independently of sample size. In current research, these statistical values are
      usually calculated at the manifest level. Calculating effect sizes at the latent
      level within a structural equation model can, however, result in more valid,
      different and potentially higher estimates. Therefore, the manifest and latent
      estimation of different types of effect sizes in a large rehabilitation research
      data set were compared. The impact of the different methods for estimating effect
      sizes in subgroups generated by indication, sex and age was demonstrated.
      Calculations were conducted using data from a meta-analysis (N=5809) in which the
      subjective health status of patients in orthopedic (N=2386), cardiological
      (N=1976) and psychosomatic rehabilitation (N=1447) was measured. The results were
      standardized effect sizes between 0.03 and 1.44 and standardized response means
      between 0.05 and 1.31 for manifest variables and standardized effect sizes
      between 0.04 and 1.58 and standardized response means between 0.07 and 1.45 for
      latent variables. Thus, latent effect sizes were generally higher, although no
      specific factor for transforming manifest into latent effect sizes seems to
      exist. Although the computation of latent effect sizes does not necessarily yield
      higher estimates, it should nonetheless be carried out as a matter of routine.

PMID- 18708844
TI  - Entering work: employment outcomes of people with developmental disabilities.
AB  - This paper provides a current snapshot of employment outcomes for individuals
      with developmental disabilities who had recently entered integrated employment
      (individual and group supported jobs) with the support of a community
      rehabilitation provider. Individual outcomes are based on an analysis of the
      National Survey of Community Rehabilitation Providers conducted between 2004 and
      2005 by the Institute for Community Inclusion at the University of Massachusetts
      in Boston. Survey results show that the majority of respondents with
      developmental disabilities worked part-time in individual jobs, predominantly in
      the entry-level service industry; earned above federal minimum wage; and received
      paid time off. Differences in employment outcomes by type of integrated
      employment model are discussed. The paper concludes with a discussion of the
      implications of the findings.

PMID- 18708845
TI  - Leisure participation for individuals living with acquired spinal cord injury.
AB  - Traditionally, rehabilitation professionals have viewed and studied leisure
      participation in terms of quantifiable activities. Advances in leisure studies
      have, however, led to recognition of the need for and value of examining leisure
      as a subjective experience too. Accordingly, this study used a qualitative
      approach to explore postinjury leisure participation for individuals living with
      acquired spinal cord injury. A secondary analysis was performed for data from a
      primary study that examined social adaptation needs related to community living
      after rehabilitation. Participants who had completed their initial rehabilitation
      at least 3 years earlier took part in in-depth, personal interviews. The analysis
      identified specific leisure activities participants had done and/or are doing
      after spinal cord injury. It also provided insight into how and why these
      activities are being done and/or not being done. Major findings are illustrated
      by participants' personal verbatim quotes. Implications and recommendations for
      further research and professional practice in rehabilitation are outlined.

PMID- 18708846
TI  - Long-term cognitive functional limitations post stroke: objective assessment
      compared with self-evaluations and spouse reports.
AB  - This study was part of a Swedish interdisciplinary research project targeting
      accessibility problems in public transport for people with cognitive functional
      limitations (CFLs). The objective was to describe and compare different
      assessment perspectives of long-term CFLs among community citizens having had
      CFLs in the acute stroke phase but with moderate physical limitations. Eighty
      four participants in ordinary housing 18-36 months post stroke, initially sampled
      from a national quality stroke register, received data collection home-visits.
      The Cognistat screening instrument was used for an objective assessment, and a
      study-specific questionnaire for self-evaluations of CFLs. A revised form of the
      latter questionnaire was used for reports from spouses of a subset of 30
      participants. The agreement between self-evaluated CFLs and spouse reports was
      analysed by percentage agreement and Cohen's kappa, whereas differences in
      ratings were tested by McNemar's test, as were differences between objective and
      self-evaluated/spouse-reported occurrence of CFLs. Regardless of the different
      perspectives applied, CFLs were frequent. In absence of significant difference in
      ratings, the percentage agreement between self-evaluations and spouse reports was
      good or very good, whereas kappa values were less encouraging. Overall,
      participants and spouses expressed more CFLs, as compared with the screening.
      Most consistency was demonstrated for the area of calculation. When researchers
      and clinicians solely rely on cognitive screenings in their investigations, there
      is a considerable risk for underestimations of CFLs.

PMID- 18708847
TI  - Adaptation of the Shoulder Disability Questionnaire to the Turkish population,
      its reliability and validity.
AB  - The objective of this study was to adapt the Shoulder Disability Questionnaire
      (SDQ) for use in Turkey, and to test its reliability and validity. Eighty
      patients with shoulder pain were included in the study. Pain severity at rest,
      with motion and during sleeping was assessed by using a numeric pain scale. The
      shoulder's active and passive range of motion were measured by a goniometer and
      recorded. The Constant-Murley scale was used for functional assessment. The
      Turkish version of the SDQ, which was adapted by using guidelines, was completed
      by the patients. To assess reproducibility, the SDQ was completed by 32 patients
      who did not improve 1 week later. The reliability of the adapted version was
      good, with high internal consistency (Cronbach's alpha=0.76) and test-retest
      reliability (Pearson's correlation coefficient=0.88). The Turkish version of the
      SDQ was found to have a moderate correlation with pain at rest, with motion and
      during sleeping. The Turkish version of the SDQ was found to be reliable and
      valid. The moderate correlation of the questionnaire with clinical parameters
      including pain shows its validity, but the questionnaire should be tested
      extensively for detecting changes within time, for use in the follow-up and
      clinical practice.

PMID- 18708848
TI  - Quality of life of people with spinal cord injury in Northern India.
AB  - This is a prospective longitudinal descriptive study to prospectively evaluate
      quality of life (QoL) in the spinal cord injury (SCI) population in Northern
      India and identify any association between clinical variables and QoL; and,
      finally, to see the impact of remedial measures taken to improve QoL over time.
      Fifty persons with SCI were surveyed for medical problems, neurological status
      and social adjustments in Northern India. QoL was determined on the Global QoL
      scale (Visual Analogue Scale) and follow-up assessment was performed 6 months
      later to examine the impact of remedial measures over time. Thirty-six (72%) men
      and 14 (28%) women participated. Mean age and duration of injury were 37.7 and
      3.7 years, respectively. Bladder problems (44%), bedsores (36%), gastrointestinal
      problems (56%), neuropathic pain (42%) and spasticity (60%) were the most common
      medical problems. Age, education, marital status and duration of injury were not
      associated with significant difference on QoL scores. Female sex, employment,
      mobility, autonomy, cordial partner relations and good social adjustment were
      associated with higher scores of QoL. Mean Global QoL scores were 54.3 and 63.7
      at the initial survey and at the 6-month follow-up survey, respectively. In a
      community-based sample of SCI in Northern India, a good-to-fair QoL was found. It
      is reasonable to believe that understanding and taking appropriate remedial
      measures through more comprehensive rehabilitation programmes will play a vital
      role in enhancement of QoL in persons with SCI.

PMID- 18708849
TI  - Whole body vibration: a new therapeutic approach to improve muscle function in
      cystic fibrosis?
AB  - Disease progression in cystic fibrosis (CF) leads to muscle wasting and loss of
      muscle function. The aim of this prospective pilot study was to evaluate the
      effects of whole body vibration (WBV) on muscle function in adult patients with
      CF. Ten patients (three males; seven females) of the CF Center Cologne, Germany,
      have completed the 3-month study (age: 24-47 years; forced expiratory volume in 1
      s (FEV1) 17-109% predicted (49+/-29) and body mass index (BMI) 16.6-24.4 kg/m2
      (19.3+/-2.5). WBV was provided by a vibration platform (Galileo 2000). The
      patients were standing in an upright position receiving vertical vibration of
      frequencies between 20 and 25 Hz. The vibration exercise evokes muscle
      contractions via stretch reflexes improving muscular activity. The training
      schedule consisted of three 3-min sessions twice a day, 5 days per week for 3
      months. Every 4 weeks the following tests were carried out: FEV1, forced vital
      capacity (FVC), BMI, chair-rising test (CRT), one-leg and two-leg jump test as
      well as maximal isometric grip force. The study has been approved by the local
      ethics committee. After 3 months of WBV all parameters in the CRT significantly
      improved: chair-rising time (P=0.03), maximal force (P=0.02), maximal power
      (P=0.01) as well as velocity (P=0.02). The peak jump force (P=0.02) and velocity
      (P=0.01) of the two-leg jump significantly improved. Parameters in the one-leg
      jump as well as maximal isometric grip force showed no significant improvement.
      Weight and BMI showed a slightly positive trend whereas FEV1 and FVC did not
      significantly change. Any change in mechanographic parameters did not correlate
      with FEV1 or FVC in this study. These results demonstrate that WBV can improve
      muscle function in CF patients.

PMID- 18708850
TI  - Achieving a minimally important difference in physical function during pediatric
      inpatient rehabilitation.
AB  - Our objectives were to examine the proportion of children who achieved a
      minimally important difference (MID) in physical function during inpatient
      rehabilitation and to identify factors related to achievement of MID. For a
      consecutive series of 452 inpatient admissions to a pediatric rehabilitation
      hospital in the northeastern United States, change scores were calculated by
      subtracting Pediatric Evaluation of Disability Inventory (PEDI) self-care and
      mobility functional skills and caregiver assistance admission scores from
      discharge scores and then evaluated for MID. Logistic regression analyses were
      used to determine the contributions of demographic and clinical variables as
      predictors of MID for each PEDI scale. More than 55% of the children achieved
      MID. The highest proportion of children achieving MID was in mobility functional
      skills (78%) and caregiver assistance (67%). Children who were older at admission
      (>10 years) had a greater chance of achieving MID on all scales. In addition,
      associated with achieving MID were longer length of stay, lower admission PEDI
      score, and a diagnosis of brain injury. More than half of all children admitted
      achieved MID in physical function. In this pediatric inpatient rehabilitation
      center, older children with brain injury who have low functional abilities at
      admission, and are able to extend their length of stay for a safe, planned
      discharge are most likely to achieve MID. Identifying children who are most
      likely to make functional progress can help program administrators and clinicians
      set realistic functional goals and expectations for an episode of inpatient care.

PMID- 18708851
TI  - Fear of falling in stroke patients: relationship with previous falls and
      functional characteristics.
AB  - The objectives of this study were to determine the relationship between fear of
      falling and functional characteristics of patients after stroke as well as to
      determine what characterizes fallers who score high fall-related self-efficacy,
      and nonfallers who score low fall-related self-efficacy. Patients (n=140) treated
      in a stroke unit during a 12-month period were included. On follow-up, fallers
      were identified and patients answered the questions in the Falls Efficacy Scale,
      Swedish version (FES-S). Assessments of motor capacity, functional mobility and
      balance were also made. In univariate analysis, low fall-related self-efficacy
      was significantly associated with increased age, female sex, earlier falls,
      visual and cognitive impairment, low mood and impaired physical function. In
      multivariate analysis, only earlier falls and physical function remained
      significant. Twenty percent of the patients scored low fall-related self-efficacy
      without having experienced a fall, and 11% who experienced a fall scored high
      fall-related self-efficacy. Impaired physical function was significantly
      associated with scoring low fall-related self-efficacy, for both fallers and
      nonfallers. Fear of falling is significantly associated with poor physical
      function and earlier falls. Falls Efficacy Scale, Swedish version could add
      useful information to a fall risk analysis. Patients scoring low fall-related
      self-efficacy should be offered fall prevention measures whether they have fallen
      or not.

PMID- 18708853
TI  - Magnetic resonance imaging of the ankle at 3.0 Tesla and 1.5 Tesla in human
      cadaver specimens with artificially created lesions of cartilage and ligaments.
AB  - PURPOSE: To compare magnetic resonance imaging of the ankle joint at 1.5 Tesla
      (T) and 3.0 T in the assessment of cartilage and ligament pathology in fresh
      human cadaver specimens. MATERIALS AND METHODS: The study was performed in line
      with institutional and legislative requirements; all donors had dedicated their
      body for educational and research purposes before death. Thirteen fresh human
      cadaver ankle joints were imaged at 1.5 T and 3.0 T using an optimized clinical
      ankle protocol consisting of T1-weighted (T1-w), fat-saturated (fs) T2-w, and
      short tau inversion recovery fast spinecho (FSE) sequences. For dedicated
      cartilage imaging, fs-intermediate (IM)-w FSE, fs-spoiled gradient echo, and
      balanced free precession steady state sequences were acquired. Artificial
      cartilage and ligament lesions were created in 6 and 5 specimens, respectively.
      MR imaging was repeated in those ankles. Four radiologists independently assessed
      pathology in all image datasets. Macroscopic findings after dissection served as
      a reference standard. RESULTS: Sensitivities and ROC-values were higher at 3.0 T
      for detecting cartilage pathology (sensitivity up to 0.71 at 3.0 T vs. 0.49 at
      1.5 T; AZ up to 0.88 vs. 0.74; both differences P < 0.05) and highest for the fs
      IM FSE sequence at 3.0 T. Average sensitivity for detecting ligament pathology
      was higher at 3.0 T (0.69 vs. 0.50; P < 0.05). Specificity was high among all
      protocols and both field strengths for assessing ligament and cartilage pathology
      (>0.95). CONCLUSION: Compared with 1.5-T imaging, the 3.0-T imaging of the ankle
      joint at improved diagnostic performance in assessing cartilage significantly and
      there was a higher sensitivity for assessing ligamentous pathology.

PMID- 18708854
TI  - Diffusion tensor magnetic resonance imaging of the human calf: comparison between
      1.5 T and 3.0 T-preliminary results.
AB  - OBJECTIVES: To compare diffusion tensor-magnetic resonance imaging (DT-MRI) of
      human calf muscles at 1.5 T and 3.0 T, and to measure a number of quantitative
      parameters to characterize diffusion anisotropy in organized muscle tissue using
      similar imaging parameters. METHODS AND MATERIALS: After Institutional Review
      Board approval and informed consent, five healthy volunteers were studied.
      Imaging was performed on both 1.5 T and 3.0 T MR systems using the similar
      imaging protocol. Diffusion-sensitized single-shot spin-echo echo planar imaging
      pulse sequences were used to collect 2-dimensional images through the calf.
      Imaging was performed using b-values of 0, 300, 500, and 700 s/mm. Image analyses
      and tensor calculations were performed offline using DT imaging studio (Johns
      Hopkins University, Baltimore, MD). The eigenvalues (lambda1, lambda2, lambda3),
      trace of the diffusion tensor (TrD), fractional anisotropy, relative anisotropy,
      and volume ratio were calculated in 3 different calf muscles (medial and lateral
      gastrocnemius and soleus). Signal-to-noise ratios (SNRs) were compared for both
      field strengths (1.5 T and 3.0 T), the different muscles and all b-values. A
      regression analysis was performed to look at within-subject effects (linear mixed
      effect model). RESULTS: No significant differences were found between all
      quantitative measured DT-MRI parameters, b-values, and muscle groups at 3.0 T and
      1.5 T (P = 0.105; P = 0.719). The mean of SNR on the 2 different field strengths
      (3.0:1.5 T) was 1.64, which was significantly different (P < 0.0001). Significant
      differences in SNR in all 3 muscles were found between sequences using b = 300
      s/mm and 700 s/mm (P < 0.001; P = 0.006) and between sequences using b = 300 s/mm
      and 500 s/mm (P < 0.001; P = 0.03), and 500 s/mm and 700 s/mm (P = 0.005; P =
      0.03), respectively, for medial gastrocnemius and soleus muscle. CONCLUSIONS:
      This study demonstrates useful parameters to perform DT-MRI at 1.5 T and 3.0 T.
      DT-MRI at 1.5 T and 3.0 T provide in vivo validation of quantitative structural
      analysis of human skeleletal muscle.

PMID- 18708855
TI  - In vivo biochemical 7.0 Tesla magnetic resonance: preliminary results of dGEMRIC,
      zonal T2, and T2* mapping of articular cartilage.
AB  - INTRODUCTION: Ultra-high-field whole-body systems (7.0 T) have a high potential
      for future human in vivo magnetic resonance imaging (MRI). In musculoskeletal
      MRI, biochemical imaging of articular cartilage may benefit, in particular.
      Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping have shown
      potential at 3.0 T. Although dGEMRIC, allows the determination of the
      glycosaminoglycan content of articular cartilage, T2 mapping is a promising tool
      for the evaluation of water and collagen content. In addition, the evaluation of
      zonal variation, based on tissue anisotropy, provides an indicator of the nature
      of cartilage ie, hyaline or hyaline-like articular cartilage.Thus, the aim of our
      study was to show the feasibility of in vivo dGEMRIC, and T2 and T2* relaxation
      measurements, at 7.0 T MRI; and to evaluate the potential of T2 and T2*
      measurements in an initial patient study after matrix-associated autologous
      chondrocyte transplantation (MACT) in the knee. MATERIALS AND METHODS: MRI was
      performed on a whole-body 7.0 T MR scanner using a dedicated circular
      polarization knee coil. The protocol consisted of an inversion recovery sequence
      for dGEMRIC, a multiecho spin-echo sequence for standard T2 mapping, a gradient
      echo sequence for T2* mapping and a morphologic PD SPACE sequence. Twelve healthy
      volunteers (mean age, 26.7 +/- 3.4 years) and 4 patients (mean age, 38.0 +/- 14.0
      years) were enrolled 29.5 +/- 15.1 months after MACT. For dGEMRIC, 5 healthy
      volunteers (mean age, 32.4 +/- 11.2 years) were included. T1 maps were calculated
      using a nonlinear, 2-parameter, least squares fit analysis. Using a region-of
      interest analysis, mean cartilage relaxation rate was determined as T1 (0) for
      precontrast measurements and T1 (Gd) for postcontrast gadopentate dimeglumine [Gd
      DTPA(2-)] measurements. T2 and T2* maps were obtained using a pixelwise,
      monoexponential, non-negative least squares fit analysis; region-of-interest
      analysis was carried out for deep and superficial cartilage aspects. Statistical
      evaluation was performed by analyses of variance. RESULTS: Mean T1 (dGEMRIC)
      values for healthy volunteers showed slightly different results for femoral [T1
      (0): 1259 +/- 277 ms; T1 (Gd): 683 +/- 141 ms] compared with tibial cartilage [T1
      (0): 1093 +/- 281 ms; T1 (Gd): 769 +/- 150 ms]. Global mean T2 relaxation for
      healthy volunteers showed comparable results for femoral (T2: 56.3 +/- 15.2 ms;
      T2*: 19.7 +/- 6.4 ms) and patellar (T2: 54.6 +/- 13.0 ms; T2*: 19.6 +/- 5.2 ms)
      cartilage, but lower values for tibial cartilage (T2: 43.6 +/- 8.5 ms; T2*: 16.6
      +/- 5.6 ms). All healthy cartilage sites showed a significant increase from deep
      to superficial cartilage (P < 0.001). Within healthy cartilage sites in MACT
      patients, adequate values could be found for T2 (56.6 +/- 13.2 ms) and T2* (18.6
      +/- 5.3 ms), which also showed a significant stratification. Within cartilage
      repair tissue, global mean values showed no difference, with 55.9 +/- 4.9 ms for
      T2 and 16.2 +/- 6.3 ms for T2*. However, zonal assessment showed only a slight
      and not significant increase from deep to superficial cartilage (T2: P = 0.174;
      T2*: P = 0.150). CONCLUSION: In vivo T1 dGEMRIC assessment in healthy cartilage,
      and T2 and T2* mapping in healthy and reparative articular cartilage, seems to be
      possible at 7.0 T MRI. For T2 and T2*, zonal variation of articular cartilage
      could also be evaluated at 7.0 T. This zonal assessment of deep and superficial
      cartilage aspects shows promising results for the differentiation of healthy and
      affected articular cartilage. In future studies, optimized protocol selection,
      and sophisticated coil technology, together with increased signal at ultra-high
      field MRI, may lead to advanced biochemical cartilage imaging.

PMID- 18708856
TI  - Peripheral magnetic resonance angiography (MRA) with continuous table movement at
      3.0 T: initial experience compared with step-by-step MRA.
AB  - PURPOSE: To compare a standard step-by-step and a newly developed continuous
      table movement (CTM) technique for peripheral magnetic resonance angiography
      (MRA) at a 3.0-Tesla MR system equipped with a matrix coil system. MATERIALS AND
      METHODS: We included 14 consecutive patients referred for peripheral MRA with
      clinical symptoms of peripheral arterial occlusive disease Fontaines stages II
      IV. All of them underwent both step-by-step MRA and CTM-MRA in one session.
      Patients with impaired renal function (calculated glomerular filtration rate <30
      mL/min) were not included. All examinations were performed on a 3.0-Tesla MR
      system. Maximal contrast agent volume was 31.5 mL (1.5 mL testbolus, 15 mL/MRA
      technique). For both techniques the same biphasic CA injection protocol was used,
      first 8 mL were injected at a flow rate of 1.5 mL/s directly followed by 7 mL at
      0.8 mL/s again followed by 25 mL of saline also at 0.8 mL/s. Spatial resolution
      of the CTM-MRA datasets was technically limited to 1.2 mm(3), step-by-step MRA
      reached 1.4 x 1.1 x 1.2 mm(3) in the abdominal station, 0.9 x 0.9 x 0.9 mm(3) in
      the most distal calf station. First CTM-MRA datasets were read and findings
      thereafter correlated with the step-by-step MRA datasets. Examination time of
      both examinations were recorded and compared. RESULTS: All datasets could be
      evaluated. The first 4 CTM-MRA cases were limited by incorrect timing in the most
      distal vessels obscuring distinct atherosclerotic changes of those vessels.
      Because of the absence of multiple localizers and subtraction masks examination
      time was considerably shorter when using the CTM-MRA technique. Relevant findings
      that were detected by the step-by-step MRA were also detected by CTM-MRA.
      CONCLUSION: MRA with CTM is an easy applicable technique for imaging peripheral
      vessels without the need for planning different steps and field of view
      positioning, thereby reducing examination time considerably. However, the
      slightly reduced spatial resolution compared with standard step-by-step MRA is a
      drawback especially in the most distal calf vessels.

PMID- 18708857
TI  - Feasibility of gadofosveset-enhanced steady-state magnetic resonance angiography
      of the peripheral vessels at 3 Tesla with Dixon fat saturation.
AB  - INTRODUCTION: To investigate the feasibility and image quality of gadofosveset
      enhanced steady-state peripheral MR-angiography using Dixon fat saturation in
      comparison to spectral fat saturation. MATERIALS AND METHODS: After Institutional
      Review Board (IRB) approval, 10 healthy volunteers underwent peripheral MR
      angiography at 3.0 T during the steady state 50 minutes after gadofosveset
      injection. A steady-state-adapted volume interpolated breathhold examination
      sequence with an isotropic spatial resolution of 1 mm was acquired with 2-point
      Dixon fat saturation (DixFS, acquisition time 52 seconds) and with conventional,
      spectral fat saturation (SFS, acquisition time 58 seconds). The quality of the
      images was rated on an ordinal 4-point scale (4, very good) by 2 radiologists in
      consensus. The signal-to-noise ratios (SNRs) of the vessels, the fat, and the
      muscles as well as the contrast-to-noise-ratio (CNR) between vessels, fat, and
      muscle were determined. Paired P tests were performed for statistical analysis
      with a significance level of P < 0.05. RESULTS: Diagnostic image quality was
      achieved in all examinations. The image quality of the DixFS images was rated
      superior (median 4) over the SFS images (median 3; P = 0.03). The SNR of muscles
      and vessels was 40% higher with DixFS (P < 0.008), whereas the SNR of fat was
      decreased by 40.3% from 40.7 with SFS to 22.4 with DixFS (P < 0.0001). The CNR
      (fat/muscle) of the DixFS images of 84.1/71.7 was significantly higher than the
      CNR of the SFS images of 47.7/47.4 (P < 0.001). DISCUSSION: Two-point Dixon fat
      suppression for MR-angiography during the steady state after the administration
      of gadofosveset is feasible with superior image quality and more than 50%
      increase in CNR (fat/muscle) compared with spectral fat saturation without an
      additional time penalty.

PMID- 18708858
TI  - Feasibility of peripheral contrast-enhanced magnetic resonance angiography at 3.0
      Tesla with a hybrid technique: comparison with digital subtraction angiography.
AB  - PURPOSE: To prospectively determine feasibility and diagnostic accuracy of 3D
      contrast-enhanced MR-angiography (CE-MRA) at 3.0 tesla (T) in patients with
      peripheral arterial occlusive disease. Digital subtraction angiography (DSA) was
      used as reference standard. MATERIAL AND METHODS: Thirty consecutive patients
      with suspected peripheral arterial occlusive disease were examined on a 3.0 T MR
      system by using the integrated whole body coil. A 4-station examination protocol
      in hybrid technique was chosen, containing 2 gadodiamide injections, the first
      one for imaging the calf and foot arteries (single-step technique) and the second
      injection for the visualization of the aortoiliacal and femoral arteries (bolus
      chase MRA). All patients underwent DSA within the following 48 hours. The
      arterial tree of each leg was divided in 15 segments and 4 anatomic regions
      (iliacal, femoral, popliteal/proximal calf, distal calf/foot). Two radiologists
      analyzed the MR-images with regard to image quality, grade of stenosis, and
      venous overlap. DSA-images were analyzed by 2 radiologists in consensus with
      regard to the stenosis grade. RESULTS: Eight hundred eighty-five and 884 of 889
      arterial segments at CE-MRA were rated with excellent or good diagnostic image
      quality by observer 1 and observer 2, respectively. In only 3 segments image
      quality was affected by venous contamination. Sensitivity of CE-MRA for
      determination of relevant arterial stenoses (50%-99%) and occlusions--as compared
      with DSA--was 95.3% (both observer) and specificity was 98.5% and 97.8% for
      observer 1 and observer 2, respectively. CONCLUSION: Peripheral hybrid CE-MRA at
      3.0 T is feasible and proved to be reliable at depiction of stenoses and
      occlusions of the whole pelvic and lower leg arterial system.

PMID- 18708859
TI  - Low dose pedal magnetic resonance angiography at 3 tesla with time-resolved
      imaging of contrast kinetics: a feasibility study.
AB  - OBJECTIVES: To assess the feasibility of low-dose time-resolved imaging of
      contrast kinetics (TRICKS) magnetic resonance (MR) angiography of the pedal
      vasculature at 3.0 Tesla (T) using a head coil. MATERIALS AND METHODS: Eleven
      healthy volunteers were imaged using TRICKS MR angiography at 3.0 T with both
      feet positioned in a head coil. A dose of 7 mL was used for each of 3
      acquisitions: images were obtained of each foot in the sagittal plane, and then
      both feet were imaged simultaneously in the transverse plane. The following
      parameters were used for acquisition: (TR/TE 4.7 milliseconds/ 1.3 milliseconds,
      field of view = 28 cm, Flip angle = 30 degrees, 384 x 256 matrix, section
      thickness = 1.6 mm, Bandwidth = 19.23). The dorsalis pedis, plantar arch, distal
      posterior tibial, lateral tarsal, and medial plantar arteries were graded for
      visualization, artifact, and overall image quality on a 4-point scale (1 = worst;
      4 = best). RESULTS: Superior visualization trended towards separate sagittal
      acquisitions when compared with that of bilateral transverse acquisitions for
      most of the individual vessels of the foot. Overall, separate sagittal
      acquisitions (average score = 2.9) were superior to bilateral transverse
      acquisitions (average score = 2.6). The average image quality score reflecting
      the amount of artifact was 2.6 for studies obtained using bilateral transverse
      acquisitions and 3.1 for studies obtained using separate sagittal acquisitions.
      CONCLUSION: Low-dose gadolinium multi-injection TRICKS and bolus-chase MR
      angiography at 3.0 T provides an effective and easily reproducible technique for
      imaging of the pedal vasculature in volunteers and has great potential for
      clinical application.

PMID- 18708860
TI  - Assessment and reproducibility of aortic atherosclerosis magnetic resonance
      imaging: impact of 3-Tesla field strength and parallel imaging.
AB  - OBJECTIVES: To investigate image quality and interstudy reproducibility of aortic
      atherosclerosis imaging at 1.5 T, and to explore the impact of parallel imaging
      techniques at 3 T. MATERIALS AND METHODS: Institutional review board approval and
      informed consent were obtained. Thirty-two subjects (20 normal, 12 patients with
      impaired cardiac function) underwent 4 black-blood T2-weighted imaging studies of
      the abdominal aorta: 2 conventional studies at 1.5 T, a conventional study at 3
      T, and an accelerated 3-T study with parallel imaging (SENSE). Contrast-to-noise
      ratio and image quality score (1-5 scale, 5 = highest quality) were determined
      for each study. Studies were analyzed for mean wall thickness and area plaque
      burden as endpoints for aortic atherosclerosis. Bland-Altman analyses were
      performed to determine interstudy reproducibility between imaging methods.
      Wilcoxon signed-rank tests were used to identify significant differences between
      methods (P < 0.05). RESULTS: Image quality scores were comparable between 1.5 T
      and 3 T with SENSE (4.0 +/- 0.6 vs. 4.2 +/- 0.6, P = 0.21). Bland-Altman
      reproducibility for mean wall thickness was -0.03 mm +/- 0.15 (1.5 T vs. 1.5 T),
      0.01 mm +/- 0.17 (1.5 T vs. 3 T without SENSE), and -0.01 mm +/- 0.18 (1.5 T vs.
      3 T with SENSE), P = 0.83. Detection of the presence or absence of plaque was
      comparable. Bland-Altman reproducibility for area plaque burden was -0.02% +/-
      0.32% (1.5 T vs. 1.5 T), 0.06% +/- 0.41% (1.5 T vs. 3 T without SENSE), and 0.11%
      +/- 0.33% (1.5 T vs. 3 T with SENSE), P = 0.41. CONCLUSION: Black-blood MR
      imaging of aortic atherosclerosis is very reproducible. Parallel imaging at 3 T
      permits shorter scan time compared with conventional 1.5-T imaging with
      comparable measures of atherosclerosis extent.

PMID- 18708861
TI  - Contrast-enhanced whole-heart coronary magnetic resonance angiography at 3.0 T:
      comparison with steady-state free precession technique at 1.5 T.
AB  - OBJECTIVES: To compare contrast-enhanced whole-heart coronary MR angiography
      (MRA) at 3.0 T and noncontrast steady-state free precession coronary MRA at 1.5 T
      in the same volunteers. MATERIALS AND METHODS: Nine healthy volunteers underwent
      both coronary MRA using 3D FLASH with slow infusion of MultiHance at 3.0 T and 3D
      TrueFISP sequence at 1.5 T. Neither beta-blockers nor nitroglycerine was
      administered in any of the imaging sessions. The same spatial resolution and
      heart coverage were used at both field strengths. Acquisition time, signal-to
      noise ratio of coronary blood, contrast-to-noise ratio (CNR) between coronary
      blood and surrounding myocardium or connecting tissue, scores of image quality,
      coronary artery sharpness, and coverage of coronary segments for the 2 techniques
      were analyzed and statistically compared. RESULTS: There were no significant
      differences in heart rate (68 +/- 10 vs. 63 +/- 6 beats/min, P > 0.05) and
      navigator efficiency (34.1% +/- 7.7% vs. 34.8% +/- 9.2%, P > 0.05) at 3.0 T and
      1.5 T coronary MRA during the data acquisition. The average acquisition time of
      the 3.0 T coronary MRA was significantly shorter than that of the1.5 T coronary
      MRA (9.7 +/- 2.3 vs. 14.6 +/- 3.5, P < 0.05). The mean score of image quality and
      vessel sharpness at 3.0 T was similar to that at 1.5 T (2.8 +/- 1.0 vs. 3.0 +/-
      1.0 and 0.63 +/- 0.15 vs. 0.61 +/- 0.13, respectively. P > 0.05). There was no
      significant difference between the number of visible coronary segments of the
      major coronary arteries at 3.0 T and 1.5 T (64/81 vs. 62/81, P > 0.05). However,
      the number of visible main coronary branches at 3.0 T was significantly higher
      than that at 1.5 T (18/54 vs. 7/54, P < 0.05). The overall signal-to-noise ratio
      at 3.0 T was significantly lower than that at 1.5 T (40.9 +/- 4.7 vs. 60.9 +/-
      3.4, P < 0.01), whereas the overall CNR at 3.0 T was significantly higher than
      that at 1.5 T (35.4 +/- 3.3 vs. 28.8 +/- 6.4, P < 0.05). CONCLUSION: Contrast
      enhanced whole-heart coronary MRA at 3.0 T demonstrated less acquisition time,
      higher CNR, and better depiction of coronary segments compared with steady-state
      free precession coronary MRA at 1.5 T. Patient studies are required to evaluate
      the clinical value of the technique.

PMID- 18708862
TI  - Using a contrast-enhanced imaging sequence at 3-minute delay in 3-T magnetic
      resonance imaging for acute infarct evaluation.
AB  - OBJECTIVES: To investigate the performance of a delayed-enhancement (DE) sequence
      adapted for a 3-minute delay after bolus injection of a contrast media in cardiac
      magnetic resonance imaging (MRI) in acute reperfused myocardial infarction.
      MATERIALS AND METHODS: Sixty-three patients with recent myocardial infarction
      underwent contrast-enhanced MRI. Sequences of first-pass (FP) perfusion imaging
      and DE imaging at 3 and 15 minutes were performed at the acute phase. Of these
      patients, 49 had a follow-up cardiac magnetic resonance examination. Infarct
      sizes were quantified by 2 experienced users with a 17-segment model at the acute
      phase (at FP and at 3- and 15-minute delay) and at the chronic phase (at 15
      minutes because only fibrous areas hyperenhance late). Areas of hypoenhancement
      and hyperenhancement were also calculated. Results from the 3-minute imaging
      sequence at the acute phase were compared with the FP (taking into account dark
      signal areas), with the 15-minute DE imaging sequence results at the acute phase
      [taking into account dark signal and hyperenhanced (white plus dark signal)
      areas] and with the 15-minute DE imaging sequence from the chronic phase (taking
      into account hyperenhanced areas). Least squares regression and Bland-Altman
      plots were performed for the comparisons. RESULTS: For the evaluation of
      hyperenhancement, the comparison between imaging sequence results at 3 minutes
      versus 15-minute DE at the acute phase (respectively, at the chronic phase) shows
      a good correlation (r(2) = 0.941; respectively r(2) = 0.862, at the chronic
      phase) and the Bland-Altman plot indicates a good concordance (m =-0.43; SD =
      2.69; respectively m = 2.76; SD = 3.92); For the evaluation of hypoenhancement,
      the comparison between imaging sequence results at 3 minutes versus FP
      (respectively, 15 minutes at the acute phase) also shows a good correlation (r(2)
      = 0.751; respectively r(2) = 0.71) and the Bland-Altman plot indicates a good
      concordance (m = -1.06; SD = 3.34; respectively m = 2.90; SD = 3.11). Finally,
      the interobserver study provides a very good kappa coefficient (kappa = 0.82),
      and good kappa coefficients from the intraobserver study (kappa1 = 0.78 and
      kappa2 = 0.86). CONCLUSIONS: The use of a delayed contrast-enhanced sequence
      adapted for a 3-minute delay after the bolus injection has the potential to
      obtain quickly reliable information comparable with the perfusion delay at FP and
      reliable information from the infarct size at 15 minutes and at the chronic
      phase.

PMID- 18708863
TI  - Infections in the perinatal period.

PMID- 18708864
TI  - Possible application of animal models for the long-term investigation of shift
      work of healthcare professionals.

PMID- 18708865
TI  - Why won't this newborn be breast-fed?

PMID- 18708866
TI  - "Conscience" clauses: the rights and responsibilities of a nurse.

PMID- 18708867
TI  - Nursing intuition and avoiding the cascade to a crisis.

PMID- 18708868
TI  - Best practices in perinatal nursing: implementing safe and effective practices
      for second-stage labor.

PMID- 18708869
TI  - Cytokines in the perinatal and neonatal periods: selected aspects.

PMID- 18708870
TI  - Preparing for pandemic influenza.
AB  - Influenza is a highly contagious, acute febrile respiratory illness that results
      in global morbidity and mortality annually. Avian influenza (H5N1) has the
      potential to cause a pandemic. Avian influenza's epidemiology and clinical
      description, including common signs/symptoms, transmission, vaccination, and
      treatment, are presented. Recommended isolation practices for labor and delivery,
      and proper procedures for identifying and managing infected patients are
      provided. Potential maternal and newborn outcomes related to influenza and avian
      influenza are discussed. Pandemic planning issues are outlined, including
      hospital surge capacity, medical equipment and staffing availability, and the
      need for altered standards of care. Communities need to designate sites (whether
      in hospital or in alternative care centers) for labor and delivery services as
      part of their disaster plan. Pregnant women and newborns are vulnerable groups
      during routine times and are expected to be disproportionately affected during a
      pandemic in terms of morbidity and mortality. Therefore, it is essential that
      hospitals and communities take steps to protect these vulnerable groups as part
      of the disaster planning process. It is not known whether or when a pandemic will
      occur, but perinatal and neonatal nurses should become familiar with avian
      influenza's clinical description and proper infection control procedures to halt
      potential disease spread.

PMID- 18708872
TI  - Tuberculosis: a breast-feeding challenge.
AB  - A recent resurgence of tuberculosis in the world community has brought the
      disease into the forefront of communicable disease control. Acknowledging the
      proven benefits of breast-feeding infants, the question of compatibility arises
      regarding the safety of breast-feeding an infant in the event of active
      tuberculosis disease in the mother. This article will discuss the emerging trends
      of tuberculosis disease and review the evidence that addresses the issues of
      safety while breast-feeding during tuberculosis treatment.

PMID- 18708873
TI  - Infectious diseases in pregnancy: issues of screening, prevention, and treatment.
AB  - Infectious disease recommendations that play a part in care during birth, or
      among hospitalized antepartum women, are updated with new information as evidence
      becomes available. At the time of hospitalization during pregnancy, attention to
      testing and treatment can prevent the transmission of infections to the newborn,
      can improve the management of the mother's health, and is an increasingly
      important aspect of patient safety initiatives. Obstetric and perinatal nurses
      who are aware of current recommendations play a critical role in disease
      prevention. This article discusses issues that are relevant for maternal child
      healthcare practitioners. Examples are used to illustrate concerns of particular
      importance during pregnancy, such as antibiotic-resistant infections, vaccine
      preventable illness, and testing for infectious diseases.

PMID- 18708874
TI  - Nosocomial infection in neonates: inevitable or preventable?
AB  - In the neonatal intensive care unit population the nosocomial infection rate is
      highest in the lowest-birth-weight infants. It is this group of infants who
      require the most therapeutic interventions to support them leading to frequent
      invasive procedures and the longest exposure to the hospital environment.
      However, infection rates vary from one unit to another, suggesting that there are
      differences in either how infection rates are determined or the care provided in
      the various units. This article will describe nosocomial infections and rates in
      the neonatal intensive care unit and identify strategies of care to minimize the
      risks of nosocomial infection in low-birth-weight infants.

PMID- 18708876
TI  - Update on group B streptococcal infections: perinatal and neonatal periods.
AB  - Group B Streptococcus (GBS), one of the beta-Hemolytic streptococci, remains a
      leading cause of neonatal sepsis in the United States. The first consensus
      guidelines for the prevention of neonatal GBS disease were published in 1996,
      recommending intrapartum antibiotic prophylaxis on the basis of screening-based
      or risk-based strategies. Since then, there has been a 70% decrease in the rate
      of early-onset GBS disease. On the basis of evidence-validating superiority of
      this screening-based strategy, new national guidelines were released in 2002.
      Data from the Centers for Disease Control and Prevention in 2005 showed a
      continued decrease in the annual incidence of early-onset GBS infection. The
      screening-based strategy involves universal screening of all pregnant women at 35
      to 37 weeks' gestation for vaginal and rectal GBS colonization and recommends
      intrapartum antibiotic prophylaxis for all GBS carriers (unless delivered by
      planned cesarean section before the onset of labor in a woman with intact
      membranes) with penicillin-G (or ampicillin). For mothers with severe penicillin
      allergy, clindamycin or erythromycin is recommended, when GBS' sensitivity is
      known; otherwise, vancomycin is recommended. Cefazolin is recommended for
      individuals with mild penicillin allergy. Severe anaphylactic reactions to
      penicillin were extremely rare. Emergence of antibiotic resistance to penicillin
      is still a theoretical possibility. This article provides a detailed account of
      recommendations for screening, diagnosing, and treating GBS disease in newborns.

PMID- 18708877
TI  - Applications of probiotics for neonatal enteric diseases.
AB  - Probiotics are bacteria and yeast that have a beneficial effect on the
      maintenance of health. Probiotic microorganisms are inherently present in
      fermented food products. A renewed interest in probiotic therapy designed for
      both treatment and prevention of intestinal and extraintestinal disorders has
      resulted in studies in infants and children. This review focuses on the
      applications of probiotics in enteric conditions experienced by neonates and
      discusses future evaluations to develop recommendations for their use.

PMID- 18708878
TI  - Mistakes were made ... but by whom?

PMID- 18708879
TI  - Core dimensions of connectivity in public health collaboratives.
AB  - A major challenge facing state and local public health agencies is how to partner
      with other organizations, agencies, and groups to collaboratively address goals
      in population health while effectively maximizing resource sharing of the
      partners involved. Today's public health efforts require multiagency partnerships
      between both governmental and nongovernmental sectors to achieve this mission.
      However, the frequent reconfiguration of partnerships among government and
      nongovernmental agencies has left many public health managers struggling to find
      ways to both develop public health collaboratives and evaluate their success. In
      this article, we use network theory and social network analysis to outline the
      core dimensions of connectivity used to measure progress in public health
      collaboratives. Connectivity is defined as the measured interactions between
      partners in a collaborative such as the amount and quality of interactions and
      how these relationships might change over time. We also articulate how these
      measures fit into the overall process of measuring progress in public health
      collaboratives and end the article with suggestions for future research and
      development.

PMID- 18708880
TI  - Assessing regional public health preparedness: a new tool for considering cross
      border issues.
AB  - OBJECTIVE: To provide regional, state, and local public health officials a
      conceptual framework and checklist for assessing regional public health emergency
      preparedness, specifically in regard to cross-border public health preparedness
      needs. METHODS: The project had four phases that are as follows: defining the
      scope, conducting a literature review, soliciting expert opinion, and creating
      the assessment framework and checklist. A conceptual framework was developed to
      define the scope of the project on the basis of the kinds of resources likely to
      be shared across borders in a public health response (eg, data, supplies, staff),
      in support of the public health functions likely to be important in a health
      emergency (eg, epidemiology, laboratory). A literature review was then conducted
      to identify key articles and tools addressing regional preparedness. Key
      informant interviews (n = 23) were conducted with public health and emergency
      management professionals in the Pacific Northwest to identify a set of systems,
      agreements, and protocols that should be systematically considered in assessing
      regional public health preparedness. Using the literature review and themes from
      interviews, a checklist was developed. RESULTS: A checklist was developed for use
      by public health leaders, which recommends 24 specific agreements, protocols,
      systems, and management structures that should be considered to foster cross
      border public health preparedness. CONCLUSIONS: Regional public health
      preparedness represents not only the sum of state-level preparedness of the
      states in a region but also the capacity of those states to collaborate across
      state and international borders during a public health emergency. This checklist
      provides a tool to systematically consider cross-border preparedness issues.

PMID- 18708881
TI  - The skills gap in hospital management in the South African public health sector.
AB  - A lack of management capacity has been identified as the key stumbling block to
      the transformation and reconceptualization of the public sector in South Africa
      into a more effective, efficient, and responsive system of health delivery. As
      part of the overall management development process, this research aimed to
      identify the skills important for public sector health management and to evaluate
      managers' self-assessed proficiency in each of these skills. A cross-sectional
      survey using a self-administered questionnaire was conducted among hospital
      managers in the South African public health sector. Respondents were asked to
      rate the level of importance that each proposed competency had in their job and
      to indicate their proficiency in each skill. Self-assessment of levels of
      competency showed that managers felt most competent in strategic planning, people
      management, and self-management, and relatively less competent in the task
      related skills and their ability to deliver healthcare. People management, self
      management, and task-related skills were rated as being most important, followed
      by strategic management and health delivery skills, respectively. The largest
      differences between mean importance rating and mean skill rating were for people
      management skills, task-related and self-management skills. These findings
      reflect the reality of the local health service environment and the needs of
      health managers and will be useful in the conceptualization, design, and delivery
      of health management programs aimed at enhancing current and future management
      and leadership capacity in the public health sector in South Africa.

PMID- 18708882
TI  - Climate change: public health crisis or opportunity.

PMID- 18708883
TI  - The continuing first revolution in public health: infectious disease.

PMID- 18708884
TI  - Screening persons newly diagnosed with HIV/AIDS for risk of intimate partner
      violence: early progress in changing practice.
AB  - Interventions to prevent intimate partner violence (IPV), including among those
      at risk for or living with HIV/AIDS, are needed. In 2001, screening persons who
      test positive for HIV for risk of IPV was required in New York State, launching
      the first large-scale program to screen for IPV risk in conjunction with HIV
      counseling and testing (HCT). Written surveys of counselors, physicians, and
      agency supervisors explored attitudes, practices, knowledge, and training needs
      surrounding screening for risk of IPV during HCT. Most HCT providers were aware
      of screening requirements, but practice varied. Counselors were more likely to
      screen than were physicians and asked more screening questions. Despite
      guidelines, screening was generally not standardized and sporadic. IPV screening
      in conjunction with HCT is possible. Building capacity and commitment of local
      HCT providers through provision of training and by fostering partnerships with
      public health partner services staff can help overcome identified barriers to
      preventing IPV in a high-risk population.

PMID- 18708885
TI  - Early results of a statewide initiative to involve faith communities in HIV
      prevention.
AB  - In the United States, racial/ethnic health disparities persist across all leading
      health indicators. In 2005, African Americans accounted for half of all HIV/AIDS
      cases, but only 12 percent of the US population was African American. Since the
      beginning of the HIV/AIDS epidemic, the New York State Department of Health, AIDS
      Institute recognized the importance of faith communities' involvement in HIV
      prevention. A survey assessed faith community involvement in HIV prevention,
      identified barriers to involvement, and determined willingness to partner with
      HIV prevention programs. Although less than 25 percent of respondents reported
      involvement in HIV prevention, 50 percent were willing to meet with service
      providers. Those willing to meet included 74 percent of faith leaders with
      primarily African American congregants. On the basis of the survey and subsequent
      forums, a statewide initiative was created to involve faith communities in HIV
      prevention. An assessment of the statewide initiative showed that it has been
      highly effective in engaging faith community involvement, including a large
      number of African American faith communities. These findings have implications
      for future programming and can aid to further strengthen the statewide
      initiative.

PMID- 18708886
TI  - Impact of electronic laboratory reporting on hepatitis A surveillance in New York
      City.
AB  - BACKGROUND: The New York City Department of Health and Mental Hygiene (DOHMH)
      coordinates the administration of timely postexposure prophylaxis (PEP) to
      contacts of hepatitis A cases, making prompt disease reporting especially
      valuable. Electronic laboratory reporting (ELR) has been shown to improve
      timeliness of infectious disease reporting, and DOHMH began receiving hepatitis A
      reports via ELR in 2002. OBJECTIVES: (1) to quantify the increase in the
      proportion of hepatitis A reports received electronically, (2) to assess how
      implementation of ELR affected the reporting time of hepatitis A, and (3) to
      assess how changes in reporting time impacted the ability to offer timely
      prophylaxis to contacts. METHODS: We evaluated the proportion of reports received
      via ELR and the annual reporting time of all hepatitis A reports and quantified
      the individuals who received PEP from 2000 to 2006. The specific impact of ELR on
      laboratory reporting time was assessed for nine laboratories certified as of July
      2006. RESULTS: The proportion of hepatitis A reports received via ELR increased
      during the study period to 35 percent in 2006. Electronic laboratory reporting
      improved the reporting time for most of the laboratories certified to report
      electronically, with a median decrease of 17 days. In 2006, DOHMH administered
      PEP to 299 individuals; a fourfold increase from 2000. CONCLUSIONS: Electronic
      laboratory reporting provides timely disease data to health departments.
      Increased utilization of ELR can have a remarkable impact on public health
      surveillance and response.

PMID- 18708887
TI  - Tuberculosis control in a large urban jail: discordance between policy and
      reality.
AB  - OBJECTIVE: This study evaluated adherence to tuberculosis control guidelines,
      published by the Centers for Disease Control and Prevention in 1996, in a large
      urban jail. Jails are a critical locale because of high risk for tuberculosis
      transmission in a congregate setting. METHODS: Symptom screening at intake into
      the facility was systematically observed. Medical records were reviewed to
      measure timing of tuberculin skin testing (TST) and chest radiograph (CXR)
      screening. Isolation records were examined for airborne infectious isolation
      practices. Contact investigation practices were evaluated for ease of data
      retrieval and adherence to CDC guidelines. RESULTS: A TB symptom screening
      question was asked correctly during 28/97 of intake health interviews. Median
      time from intake to TST was 3 days for men and 2 days for women. Median time from
      referral to CXR was 2 days for men and 7 days for women. Delays were noted in
      diagnostic testing of 51 detainees isolated for suspected TB. Contact
      investigations lacked comprehensive procedures, data collection forms, and
      databases for managing information. CONCLUSION: Findings were used to refine
      protocols for TB control. This evaluation illustrated the need for ongoing
      assessment of adherence to TB control protocols in short-term correctional
      settings to prevent the spread of TB.

PMID- 18708888
TI  - Completeness of reporting of rabies postexposure prophylaxis in King County,
      Washington.
AB  - The completeness of rabies postexposure prophylaxis (PEP) reporting was evaluated
      in King County, Washington State. Information on rabies immune globulin
      prescriptions was obtained from hospital pharmacies associated with emergency
      departments in King County from 2003 to June 2006. Rabies immune globulin is
      given at the initiation of rabies PEP which is usually started at emergency
      departments. Because pharmacies are not regular sources of rabies PEP reporting,
      we compared pharmacy cases with cases reported via routine passive surveillance
      methods. A capture-recapture method was used to calculate the estimated number of
      unreported cases from all sources. Reporting completeness was calculated by
      dividing the number of cases reported via routine surveillance with the sum of
      reported and estimated unreported cases. Seventy-one unreported rabies PEP cases
      were identified by comparing previously reported cases with pharmacy cases. A
      total of 128 cases were estimated to have been missed by the surveillance system.
      Overall reporting completeness was 62 percent increasing to almost 80 percent in
      2005 and 2006. Our findings illustrate the importance of evaluating surveillance
      systems and suggest that it may be useful to institute active rabies PEP
      surveillance with emergency departments in addition to continuing educating
      healthcare providers and facilities about reporting.

PMID- 18708889
TI  - Comparability on knowledge, attitudes, and behaviors between STD clinic clients
      and high-risk individuals in community.
AB  - OBJECTIVES: To assess the feasibility and generalizability of STD clinic samples
      for studying STD-related knowledge, attitudes, and behaviors (KAB), and
      healthcare preferences among individuals at high risk for STDs in the same
      community. STUDY DESIGN: An STD clinic and a community sample were selected from
      each of two urban areas in New York State. At each STD clinic, 100 individuals
      were interviewed. In each community, about 400 individuals were selected by
      random-digit-dialing telephone survey during the same period. Community sample
      participants were defined as having high-risk profiles on the basis of five items
      related to their sexual behaviors. RESULTS: The STD clinic samples were younger
      and had a larger proportion of men and nonwhite people compared with the high
      risk community samples. Although the majority of STD clinic clients would seek
      healthcare at the STD clinics, high-risk community participants were more likely
      to prefer private doctors for STDs care (P < .0001 for both areas). Overall STD
      related KAB were similar between STD clinic and high-risk community samples;
      however, STD clinic clients may be more knowledgeable about specific STDs and
      more likely to feel embarrassment about getting an STD. The findings comparing
      KAB between high-risk community subjects and STD clinic attendees also varied by
      geographic location. CONCLUSIONS: STD clinic samples may not be sufficiently
      representative of community STD-related KAB collected by telephone surveys, even
      for that subset of community respondents with high-risk behaviors associated with
      STDs.

PMID- 18708890
TI  - When the cat is out of the bag: a case study in public health rationing in Oregon
      during the 2004-2005 influenza vaccine shortage.
AB  - Whereas the annual influenza season in the United States is fairly predictable,
      the influenza vaccine supply is variable, leaving providers vulnerable to supply
      and demand fluctuations each season. During the 2004-2005 influenza vaccine
      shortage, Oregon invoked Oregon Revised Statute 433-030 to target vaccine
      supplies to protect persons at highest risk for complications from influenza.
      This case study describes Oregon's efforts to ration vaccine at the point of
      administration by limiting the number of individuals eligible for vaccination. An
      evaluation of this process found that providers responded positively to the
      mandatory prioritization of vaccine recipients; however, limitations in assessing
      and affecting redistribution of privately held vaccine supplies and challenges in
      enforcement of the plan were revealed.

PMID- 18708891
TI  - Wanted: an effective public health response to hepatitis C virus in the United
      States.

PMID- 18708892
TI  - The Vote and Vax program: public health at polling places.
AB  - Although influenza-associated illness is a major cause of hospitalizations and
      death among older Americans, only half of adults aged 50 or older-for whom
      influenza vaccinations are recommended-receive an annual influenza vaccination.
      National elections, which draw a large number of older voters, take place during
      influenza vaccination season and represent an untapped opportunity for large
      scale delivery of vaccinations. In 2006, the Robert Wood Johnson Foundation
      launched a program to evaluate the feasibility of delivering influenza
      vaccinations near polling places. Twenty-five public health agencies were each
      provided grants of $8000 and asked to implement at least two Vote and Vax
      clinics. Immunizers were required to obtain prior permission from local election
      authorities and to charge fees as they would at their other community-based
      clinics. Influenza vaccination had to be made available both to voters and to
      nonvoters. On election day, the initiative delivered 13790 influenza vaccinations
      at 127 polling places in 14 states. More than 80 percent of adult vaccine
      recipients were in the Centers for Disease Prevention and Control-defined
      priority groups and 28 percent were "new" influenza vaccination recipients. Vote
      and Vax is a potentially national strategy that could significantly expand the
      delivery of influenza vaccinations.

PMID- 18708893
TI  - Monitoring change in health disparity.
AB  - Agencies and programs tasked to reduce and eliminate disparity need the best
      available methods to assess the success of their efforts. When monitoring
      disparity it is vital to be aware of how absolute and relative measures of
      disparity, and when changes are measured, can lead to different conclusions
      regarding progress. Absolute and relative disparities for homicide rates between
      Hispanics and non-Hispanic Whites were calculated on an annual basis for 1989
      through 2003. A joinpoint regression of rates was used to identify where
      significant changes occurred over the 15-year period. Absolute and relative
      changes in disparity were measured for each interval identified. The annualized
      percent changes in homicide rates for each interval were used to evaluate how
      relative rates of change in homicide affect disparity. Three distinct change
      points were found for homicide rates and changes in disparity between Hispanics
      and non-Hispanic Whites for the period 1989-2003. Intervals 2 (1991-1994) and 3
      (1994-1999) had declines in both absolute and relative disparity. Only interval 3
      had disparity reductions sufficient, if they had continued, to suggest any
      elimination of disparity within the next 5 years. Reduction in the relative
      difference between groups is the best evidence of progress toward eliminating
      disparity. The relative rate of improvement for the group with less favorable
      rate must be greater than that of the group with the more favorable rate. It is
      just as important to be aware of when disparity is being assessed in a longer
      overall trend.

PMID- 18708894
TI  - Identification of patients with arthritis and arthritis-related functional
      limitation using administrative data.
AB  - OBJECTIVE: To develop algorithms on the basis of administrative data to identify
      patients with arthritis and arthritis-related functional limitation (AFL). STUDY
      DESIGN AND SETTING: In this retrospective study, 361 enrollees of a health plan
      underwent a clinical examination to confirm arthritis and assessment of
      functional limitation on the basis of responses to the health assessment
      questionnaire. Administrative data were obtained on these subjects and included
      arthritis drugs dispensed, as well as outpatient and emergency department
      diagnoses and procedures (including radiographic studies, arthritis procedures,
      and laboratory tests). Composite risk scores for arthritis and AFL were created
      on the basis of the association of arthritis-related healthcare utilization with
      confirmed arthritis and AFL. Algorithms were then developed on the basis of the
      composite risk scores using logistic regression models. RESULTS: The algorithm
      using the arthritis composite score to identify arthritis patients had an area
      under the ROC curve (AUC) of 0.74, sensitivity of 75 percent and specificity of
      57 percent. Similarly, the algorithm using the AFL composite score to identify
      patients with AFL had an AUC of 0.73, sensitivity of 62 percent, and specificity
      of 75 percent. CONCLUSION: The developed algorithms will enable health plans to
      screen their enrollees for persons with arthritis and AFL. This will facilitate
      enrollment of patients with arthritis and AFL in disease management programs
      and/or targeted interventions.

PMID- 18708895
TI  - Risk of intimate partner violence related to individuals testing HIV positive.

PMID- 18708896
TI  - Leading in the gray zone: the story of Simone James.

PMID- 18708897
TI  - Healthiest Nation Alliance stands for a healthier nation in a healthier world.
AB  - The National Association of County and City Health Officials (NACCHO) is the
      national organization representing local health departments. NACCHO supports
      efforts that protect and improve the health of all people and all communities by
      promoting national policy, developing resources and programs, seeking health
      equity, and supporting effective local public health practice and systems.

PMID- 18708899
TI  - Posttraumatic internal jugular vein thrombosis presenting as a painful neck mass
      in a child.
AB  - An uncommon case of a pediatric traumatic internal jugular vein thrombosis is
      presented. A 7-year-old boy developed severe neck pain after falling from a bunk
      bed. Initially, the child was diagnosed and treated for a lymphadenitis with a
      possible abscess formation. Contrast-enhanced computed tomography and Doppler
      ultrasound imaging of the neck revealed the presence of an occlusive thrombosis
      of the left internal jugular vein. The patient was treated with intravenous
      antibiotics and followed closely over the next year. He had full resolution of
      his symptoms without the development of complications associated with this injury
      process. Internal jugular vein thrombosis is an uncommon and potentially life
      threatening disorder caused by various conditions. This case illustrates the need
      for a systematic approach when evaluating neck masses, and internal jugular
      venous thrombosis should be included in the differential of anterior neck
      swelling.

PMID- 18708898
TI  - Neurological consequences of vitamin B12 deficiency and its treatment.
AB  - In developed countries, the vitamin B12 deficiency usually occurs in children
      exclusively breast-fed, whose mothers are vegetarians, causing low stores of
      vitamin B12. Symptoms of vitamin B12 deficiency appear during the second
      trimester of life and include failure to thrive, lethargy, hypotonia, and arrest
      or regression of developmental skills. A megaloblastic anemia can be present. One
      half of the infants exhibit abnormal movements before the start of treatment with
      intramuscular cobalamin, which disappear 1 or 2 days after. More rarely, movement
      disorders appear a few days after treatment, whereas neurological symptoms are
      improving. These abnormal movements can last for 2 to 6 weeks. If not treated,
      vitamin B12 deficiency can cause lasting neurodisability. Therefore, efforts
      should be directed to preventing deficiency in pregnant and breast-feeding women
      on vegan diets and their infants by giving them vitamin B12 supplements. When
      preventive supplementation has failed, one should recognize and treat quickly an
      infant presenting with failure to thrive and delayed development.

PMID- 18708900
TI  - An 18-month-old girl with recurrent apneic spells.
AB  - We describe the case of an 18-month-old child with recurrent apneic episodes,
      often requiring resuscitation, who was admitted to an academic pediatric medical
      center after previous evaluations had been unrevealing.

PMID- 18708901
TI  - Thoracic disk herniation resulting in acutely progressing paraplegia in a
      pediatric patient.
AB  - BACKGROUND: Thoracic intervertebral disk herniation is an uncommon entity. Acute
      presentation of this entity in the pediatric population is exceptionally rare.
      Given the infrequent prevalence, accurate diagnosis of acute symptomatic thoracic
      disk herniation can be difficult. PURPOSE: The purpose of this article is to
      describe the presentation of acute nontraumatic thoracic disk herniation in a
      pediatric patient and the diagnostic workup and surgical management of this rare
      entity. STUDY DESIGN: This is a case report regarding a pediatric patient with
      nontraumatic acutely symptomatic thoracic disk herniation. The order of
      diagnostic studies and method of surgical decompression used are described.
      Progressive follow-up neurological improvement is detailed in the report.
      METHODS: A 16-year-old adolescent girl with acutely symptomatic paramedian disk
      herniation at T10 to T11 underwent left thoracotomy followed by microdiscectomy.
      Decompression of T10 to T11 was followed by fusion of T10 to T11 with rib strut
      graft. RESULTS: Postoperatively, the patient recovered near-complete resolution
      of bilateral lower extremity paralysis and dysesthesias. CONCLUSIONS: Thoracic
      intervertebral disk herniation is a rare phenomenon. It is a particularly
      uncommon entity in the pediatric population. As such, the diagnosis and
      management of thoracic disk herniation can be a considerable challenge. As
      illustrated in our case report, the clinician's focus should not exclusively rest
      on lumbar disk pathology as the etiology for such rapidly evolving neuromuscular
      deficits. Thoracic disk herniation must be included in the differential
      diagnosis, and appropriate diagnostic workup should be instituted in an
      expeditious manner. Plain radiographic studies may not delineate the causative
      factor of pathology, and emergent magnetic resonance imaging can aid in obtaining
      a timely diagnosis. Early intervention and decompression have been shown to
      significantly improve functional recovery.

PMID- 18708902
TI  - Thrombosis and recanalization of straight sinus.
AB  - We describe a case of a 14-year-old boy who presented to the emergency department
      with nausea, vomiting, headache, and mental status changes. Noncontrast computed
      tomography scan of the brain in the emergency department revealed bilateral
      thalamic and striatocapsular infarcts. The patient was diagnosed with possible
      thrombosis of the thalamostriate veins, which was confirmed with urgent magnetic
      resonance venography (MRV). Magnetic resonance venography revealed that the
      thrombosis was extended to the straight sinus and the internal cerebral veins.
      Thrombosis of the straight sinus in children results in a rare stroke with
      inconsistent clinical manifestations, depending on collateral venous circulation
      of the thrombosed sinus. The diagnosis is quite difficult, especially when
      symptoms are nonspecific and variable. Timely diagnosis, based on the decision of
      performing emergency magnetic resonance imaging and MRV, followed by the
      administration of anticoagulation therapy may reverse this condition as in our
      patient who made an excellent recovery.

PMID- 18708903
TI  - Acute abdomen due to twisted ovarian immature teratoma in a 7-year-old girl:
      magnetic resonance findings with histopathologic correlation.
AB  - Immature teratomas represent only the 1% of ovarian teratomas, and they are the
      third most common primitive germ cell tumor; generally, they are congenital
      lesions and affect mainly the first 2 decades. We present the case of a 7-year
      old child who came at our attention because of an acute low abdominal pain due to
      the torsion of an ovarian immature grade 1 teratoma on its pedicle. After
      ultrasound in the emergency department, preoperative evaluation was done by
      performing a magnetic resonance study, whose findings helped in suggesting the
      curative approach. The magnetic resonance imaging characteristics of the neoplasm
      are reviewed and correlated with histopathologic findings. As it was highlighted
      in our case, magnetic resonance imaging may be part of the diagnostic approach of
      this rare disease entity also in a small child in emergency.

PMID- 18708904
TI  - Cardiopulmonary resuscitation and pediatric advanced life support update for the
      emergency physician.
AB  - Although pediatric cardiopulmonary arrest is uncommon, out-of-hospital survival
      is dismal. Through international consensus conferences, the American Heart
      Association develops new treatment recommendations for cardiopulmonary
      resuscitation every few years. The recent changes in cardiopulmonary
      resuscitation and pediatric advanced life support, with some background
      information about these changes, will be reviewed.

PMID- 18708906
TI  - Children's mental health emergencies-part 3: special situations: child
      maltreatment, violence, and response to disasters.
AB  - OBJECTIVE: Children may be exposed to or even be the victims of a violent
      situation, or a disaster, and the likelihood of a child's exposure to a violent
      situation or a disaster is increasing. METHODS: A review of the literature was
      done to address key mental health issues occurring with child maltreatment,
      violence in the home, community, in the emergency department, and disasters.
      RESULTS: Although pediatric mental health issues regarding violence, disasters,
      and child maltreatment have often been overlooked or unrecognized, the
      consequences for the child in such situations can be devastating. However,
      recognition and appropriate treatment can favorably impact the child's recovery
      from exposure to such violent events or disasters. CONCLUSIONS: Recognition and
      early intervention to address the mental health issues of children in violent
      situations or disasters can help ameliorate the negative psychological sequelae
      of such events. The importance of providing mental health and social services to
      children exposed to disasters was recognized by the Pediatric Institute of
      Medicine Report.

PMID- 18708907
TI  - Pediatric emergency medicine: legal briefs.

PMID- 18708908
TI  - Pediatric emergency care in community hospitals with non-pediatric emergency
      medicine providers.

PMID- 18708909
TI  - ECGs in the ED.

PMID- 18708910
TI  - What's new in Shock, September 2008?

PMID- 18708911
TI  - Nitric oxide triggers delayed anesthetic preconditioning-induced cardiac
      protection via activation of nuclear factor-kappaB and upregulation of inducible
      nitric oxide synthase.
AB  - Nitric oxide (NO) plays a pivotal role both in triggering and mediating delayed
      protection against myocardial I/R injury during anesthetic-induced
      preconditioning (APC). However, the signaling mechanisms that underlie this
      phenomenon remain unclear. Using isoflurane as a representative anesthetic, the
      present study tested the hypothesis that NO released after anesthetic-induced
      preconditioning initiates delayed cardioprotection via activation of nuclear
      transcription factor-kappaB (NF-kappaB), leading to myocardial adaptation by
      upregulation of iNOS and increase in production of NO. Sprague-Dawley rats that
      received open-chest surgery under pentobarbital anesthesia were subject to 30 min
      of left coronary artery occlusion, followed by 120 min of reperfusion. Exposure
      to 60 min of 2.1% isoflurane inhalation with oxygen 24 h before ischemia
      significantly reduced I/R-induced myocardial infarct size that was associated
      with overexpression of iNOS protein and increased NO content in the heart. These
      protective effects were abolished by pretreatment with a NOS inhibitor, N-nitro-L
      arginine methyl ester, an NF-kappaB blocker, diethyldithiocarbamate, before
      isoflurane, or a selective iNOS inhibitor, S-methylisothiourea, before left
      coronary artery occlusion. Isoflurane exposure also evoked a robust increase in
      myocardial NO content, followed by nucleus-bound translocation of p65 or p50
      subunit of NF-kappaB and increase in NF-kappaB DNA-binding activity in heart
      tissues. These molecular events after isoflurane exposure were blocked by
      pretreatment with N-nitro-L-arginine methyl ester. We conclude that NO generated
      immediately after isoflurane exposure triggers downstream activation of NF
      kappaB, resulting in subsequent upregulation of iNOS expression and NO synthesis
      that mediate APC-induced delayed cardioprotection.

PMID- 18708913
TI  - Compartmentalization of the inflammatory response in meningococcal peritonitis.

PMID- 18708914
TI  - Disability in subacute whiplash patients: usefulness of the neck disability
      index.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To analyze the psychometric
      properties of the neck disability index (NDI), with a special emphasis in its
      factor structure, and its usefulness, in a sample of patients suffering from a
      subacute whiplash problem. SUMMARY OF BACKGROUND DATA: A valid and reliable
      instrument to assess pain-related disability would be of great help to clinicians
      and researchers interested in whiplash associated disorders. First, to better
      understand the impact of whiplash on the patient's life, and his or her progress
      over time. Second, to formulate comprehensive treatment plans, and evaluate the
      results from therapeutic actions. Finally, to follow-up patients' changes and
      improvement. The NDI could be an appropriate instrument for these purposes.
      METHODS: A convenience sample of 150 subacute whiplash patients participated.
      They were requested to complete the Catalan version of the NDI, and report about
      their pain intensity, pain interference and depression. RESULTS.: An exploratory
      factor analysis showed that the NDI can be viewed as a 2-factor instrument. The
      items and the instrument's total score were normally distributed. Internal
      consistency was also appropriate both for the total score (Cronbach's alpha:
      0.87) and the 2 subscales (0.7 for the pain and interference with cognitive
      functioning scale, and 0.83 for the physical functioning scale). Total NDI and
      subscales scores significantly correlated with pain intensity, pain interference,
      and depression. CONCLUSION: The NDI showed excellent psychometric properties in a
      sample of subacute whiplash patients. Additional research is needed to replicate
      the NDIs factor structure.

PMID- 18708915
TI  - Minimum four-year follow-up of spinal stenosis with degenerative
      spondylolisthesis treated with decompression and dynamic stabilization.
AB  - STUDY DESIGN: Prospective clinical study. OBJECTIVE: To test whether posterior
      dynamic stabilization in situ with Dynesys (Zimmer Spine, Minneapolis, MN) can
      maintain enough stability to prevent progression of spondylolisthesis in long
      term follow-up. SUMMARY OF BACKGROUND DATA: In spinal stenosis with degenerative
      spondylolisthesis, decompression and fusion are widely recommended. However,
      drawbacks of fusion remain length of surgery, blood loss, possible adjacent
      segment disease, errant instrumentation, nonunion, and pain at the bone donor
      site. The Dynesys system was introduced to stabilize the spine without adding
      bone graft for fusion. Excellent 2 years results have been reported. METHODS:
      Twenty-six consecutive patients (mean age, 71 years) with symptomatic lumbar
      spinal stenosis and degenerative spondylolisthesis underwent interlaminar
      decompression and stabilization with Dynesys. Patients were evaluated clinically
      and radiologically after a minimum follow-up of 4 years. RESULTS: Nineteen of 26
      patients could be evaluated with a mean follow-up of 52 months (range, 48-57
      months). Pain on VAS and walking distance improved significantly (P < 0.001) at 2
      years and remained unchanged at 4 years follow-up. Radiographically,
      spondylolisthesis did not progress and the motion segments remained stable, even
      in the 3 patients who showed slight screw-loosening at 2 and 4 years follow-up.
      One patient showed screw breakage with low back pain and motion at the
      instrumented level in flexion/extension views. At 4 years follow-up, 47% of the
      patients showed some degeneration at adjacent levels. Overall, patient
      satisfaction remained high as 95% would undergo the same procedure again.
      CONCLUSION: In elderly patients with spinal stenosis and degenerative
      spondylolisthesis, decompression and dynamic stabilization lead to excellent
      clinical and radiologic results. It maintains enough stability to prevent
      progression of spondylolisthesis. Because no bone grafting is necessary, donor
      site morbidity, which is one of the main drawbacks of fusion is eliminated.
      However, the degenerative disease still is progressive and degeneration at
      adjacent motion segments remains a problem.

PMID- 18708916
TI  - Correlation between centrally versus peripherally transduced venous pressure in
      prone patients undergoing posterior spine surgery.
AB  - STUDY DESIGN: Prospective clinical observational study. OBJECTIVE: To evaluate
      the correlation and agreement between peripherally and centrally transduced
      venous pressures in prone spine surgery patients. SUMMARY OF BACKGROUND DATA: In
      view of a variety of potential complications associated with the placement of
      central venous lines for the purpose of central venous pressure (CVP) monitoring,
      a number of authors have suggested that the use of peripherally transduced
      pressures (PVP) instead may yield similar results. Data confirming the validity
      of this technique for the purpose of intravascular fluid volume monitoring in
      prone patients undergoing spine surgery remain scarce. METHODS: After protocol
      approval by the internal review board, we enrolled 40 patients who underwent
      spine surgery in the prone position. CVP and PVP were recorded simultaneously.
      The data pairs were analyzed for correlation. Bland and Altman plots were created
      to evaluate the degree of agreement between the 2 modes of venous pressure
      monitoring. RESULTS: A total of 1275 data pairs were collected. The mean PVP was
      17.55 mm Hg +/- 4.93 mm Hg and the mean CVP 15.52 mm Hg +/- 4.77 mm Hg (P <
      0.001), thus yielding a mean difference of 2.04 mm Hg +/- 1.39 mm Hg. PVP and CVP
      correlated well over a wide range of pressures (r = 0.949, r = 0.920 [P <
      0.001]). A high level of agreement was found between both methods of venous
      pressure measurement. CONCLUSION: CVP and PVP correlate well under conditions
      associated with prone spine surgery. With a high level of agreement found in this
      study, PVP may represent an attractive alternative to CVP monitoring to assess
      fluid volume trends intraoperatively.

PMID- 18708917
TI  - Retroperitoneal lymphocele after anterior spinal surgery.
AB  - STUDY DESIGN: Case report; Review of Literature. OBJECTIVE: To present an
      uncommon complication after anterior lumbar surgery as well as a treatment option
      and a review of the literature. SUMMARY OF BACKGROUND DATA: A number of
      complications have been reported after anterior lumbar surgery. Common
      complications include vascular, ureteral, and neurologic injuries. The
      development of a retroperitoneal lymphocele has been previously been described,
      but details regarding evaluation, diagnosis, and treatment options are lacking in
      the literature. METHODS: The case of a single patient with a postoperative
      retroperitoneal lymphocele was identified and retrospectively reviewed.
      Permission was obtained from the patient to review and publish this information.
      A review of literature on lymphoceles and anterior lumbar complications was also
      performed using PubMed and Ovid databases. RESULTS: A 76-year-old woman underwent
      anterior interbody fusion from L2-L3-L4-L5, followed by posterior T11-L5 fusion
      for degenerative scoliosis and spinal stenosis. Six weeks after surgery, she
      presented with severe abdominal pain, nausea, and emesis. Examination revealed a
      retroperitoneal lymphocele, which was confirmed after aspiration. The patient was
      treated with a laparoscopic marsupialization procedure without recurrence. At 12
      months, the patient had no further abdominal symptoms, noted improvements in back
      and leg pain scores, and had stable radiographic findings. CONCLUSION:
      Retroperitoneal lymphocele is a rare complication after anterior lumbar interbody
      fusion. The different diagnosis should include infectious abscess, ureteral
      injury with urinoma, pancreatic injury with pseudocyst formation, and spinal
      fluid leak with pseudomeningocele. Diagnosis can be guided by serum and cyst
      fluid analysis. Although treatment options exist, surgical treatment may provide
      the most reliable results.

PMID- 18708918
TI  - A case of psoas ossification from the use of BMP-2 for posterolateral fusion at
      L4-L5.
AB  - STUDY DESIGN: Case report. OBJECTIVE: Describe a complication from the use of
      bone morphogenetic protein-2 (BMP-2) for posterolateral lumbar fusion. SUMMARY OF
      BACKGROUND DATA: N/A, case report. METHODS: The patient is a 69-year-old white
      male with a 1 year history of back and right leg pain with a foot drop due to
      spinal stenosis and a degenerative spondylolisthesis at L4-L5. Surgery for
      decompression and instrumented fusion was performed using BMP. RESULTS: Within 3
      months after surgery the patient developed pain along his iliac wing, groin, and
      greater trochanter on the right side. Work up over the next several months
      included a bone scan, radiographs, Dexa scan, computed tomography scan, and
      magnetic resonance imaging with gadolinium and fat suppression. These tests
      showed extensive bone formation in the psoas and iliacus on the right side. The
      bone has persisted at least 2 years after surgery and shows no sign of
      resorption. CONCLUSION: BMP-2 can cause heterotopic bone formation when used for
      posterolateral lumbar fusion.

PMID- 18708919
TI  - Pigmented villonodular synovitis of the zygoapophyseal joint: a case report.
AB  - STUDY DESIGN: Case report of Pigmented Villonodular Synovitis (PVNS) of a lumbar
      facet joint which presented as an incidental finding of an expansile lytic lesion
      of the L5 lamina. OBJECTIVE: Exceedingly rare is the case of PVNS affecting the
      zygoapophyseal (facet) joints of the spine. To our knowledge only 30 cases have
      to this point been reported. We will discuss clinical presentation, diagnostic
      workup, treatment, and follow-up of this rare case that was treated at our
      institution. SUMMARY OF BACKGROUND DATA: First described by Jaffe et al in 1941,
      PVNS is a relatively uncommon benign disorder of unknown etiology that is
      characterized by progressive synovial proliferation. Benign, but locally
      aggressive, it is found most commonly in the knee and other large joints. PVNS
      affecting the zygoapophyseal (facet) joints of the spine is extremely rare, and
      in our opinion suitable for reporting. METHOD: The physical examination of this
      patient showed signs and symptoms that prompted the need for a plain radiographs
      and subsequently magnetic resonance imaging (MRI). MRI showed evidence of a
      lesion in the right lamina of L5. After follow-up MRI showed an expanding lesion,
      and CT scan confirmed the lytic nature of the lesion, it was decided that an
      excisional biopsy was warranted. RESULTS.: Postoperative clinical course was
      unremarkable. The patient was ambulating the next day and was discharged home 2
      days later without neurologic deficit or local wound problems. On office follow
      up, the patient continued to have diffuse, vague low back pain. Repeat radiograph
      examination shows no further boney destruction. Repeat MRI shows no residual
      lesion. CONCLUSION: We have learned from this case that PVNS of the facet joint,
      although exceedingly rare must be considered as a possible cause of expanding
      lytic lesions of the spine.

PMID- 18708920
TI  - Survival after concurrent traumatic dislocation of the atlanto-occipital and
      atlanto-axial joints: a case report and review of the literature.
AB  - STUDY DESIGN: A case report of a patient who survived a traumatic disassociation
      of both atlanto-occipital and atlantoaxial joints. OBJECTIVE.: To describe a rare
      case of concurrent atlanto-occipital and atlantoaxial dislocation with a review
      of the related literature regarding occipitocervical dislocation. SUMMARY OF
      BACKGROUND DATA: Cases of isolated atlanto-occipital or atlantoaxial dislocation
      have typically resulted in death or devastating neurologic deficit. Survival
      after the simultaneous dislocation at both joints is extremely rare. METHODS: The
      initial evaluation, subsequent management, and surgical treatment of a 25-year
      old male who sustained a concurrent dislocation of the atlantoaxial and atlanto
      occipital joints from a motor vehicle collision are reported and the related
      literature is discussed. RESULTS: The patient was transferred to our hospital
      after initial stabilization according to Emergency Medical Service criteria and
      management based on the Advanced Trauma Life Support protocol. A complete (ASIA
      A) spinal cord injury was diagnosed on admission. Radiographic evaluation
      revealed dislocations of the atlanto-occipital and atlantoaxial joints.
      Subsequently, the patient underwent surgical stabilization with instrumented
      posterior fusion from the occiput to C5. Intraoperatively, traumatic
      pseudomeningocele was diagnosed and repaired with pericranial autograft. The
      vital function parameters currently remain stable, but the patient is ventilator
      dependent and did not regain motor or sensory function. CONCLUSION: The rapid
      response time of emergency medical services and stabilization according to the
      Advanced Trauma Life Support protocol now lead to the survival of patients with
      significant deficit from occipitocervical injuries. A high index of suspicion is
      required to appropriately manage a patient with this devastating injury in order
      to maximize the chance for survival.

PMID- 18708921
TI  - Traumatic subluxation associated with absent cervical pedicle: case report and
      review of the literature.
AB  - STUDY DESIGN: Case description. OBJECTIVES: To describe a case of traumatic
      subluxation in association with a congenitally absent cervical pedicle, and
      review the pertinent medical literature. SUMMARY OF BACKGROUND DATA: The
      congenital absence of a cervical pedicle is a relatively uncommon developmental
      anomaly that is frequently mistaken for a unilateral facet fracture-dislocation
      in the context of acute trauma. Because there is little evidence of recovery
      after surgery, and the symptoms are usually not disabling, surgery is not
      recommended for most cases. METHODS: A 62-year-old man presented with severe neck
      and right shoulder pain after falling. Plain radiographs and computed tomography
      of the cervical spine showed the typical features of a congenitally absent
      pedicle at C6 with anterolisthesis of C6 on C7. We performed anterior interbody
      fusion at C6-C7 because of persistent neck pain and progressive instability.
      RESULTS: Complete restoration of the C6-C7 subluxation was achieved with
      resolution of the presenting symptoms. At 18 months follow-up, flexion and
      extension dynamic radiographs demonstrated good alignment with solid fusion at C6
      C7. CONCLUSION: Although conservative treatment is the primary treatment for this
      clinical entity, surgery is an alternative option for those patients who fail to
      achieve recovery after conservative treatment or exhibit instability.

PMID- 18708923
TI  - Cefuroxime prophylaxis is effective in noninstrumented spine surgery: a double
      blind, placebo-controlled study.
AB  - STUDY DESIGN: Double-blind, placebo-controlled randomized clinical trial.
      OBJECTIVE: To assess the efficacy of 1 preoperative 1.5 g dose of cefuroxime in
      preventing surgical site infection after surgery for herniated disc. SUMMARY OF
      BACKGROUND DATA: Antibiotic prophylaxis was only tested in nonconclusive trials
      in this setting. METHODS: The study was conducted in 2 university hospitals in
      Switzerland. Patients were assessed for occurrence of surgical site infection
      (defined by the criteria of the Centers for Diseases Control and Prevention),
      other infections, or adverse events up to 6 months after surgery. Outcome
      measures were compared in a univariate, per-protocol analysis. RESULTS: Baseline
      characteristics were similar in patients allocated to cefuroxime (n = 613) or
      placebo (n = 624). Eight (1.3%) patients in the cefuroxime group and 18 patients
      (2.8%) in the placebo group developed a surgical site infection (P = 0.073). A
      diagnosis of spondylodiscitis or epidural abscess was made in 9 patients in the
      placebo group, but none in the cefuroxime group (P < 0.01), which corresponded to
      a number necessary to treat of 69 patients to prevent one of these infections.
      There were no significant adverse events attributed to either cefuroxime or
      placebo. CONCLUSION: A single, preoperative dose of cefuroxime significantly
      reduces the risk of organ-space infection, most notably spondylodiscitis, after
      surgery for herniated disc.

PMID- 18708924
TI  - A simple disc degeneration model induced by percutaneous needle puncture in the
      rat tail.
AB  - STUDY DESIGN: : We evaluated the degenerative changes to rat tail vertebral discs
      induced by percutaneous needle puncture, and we compared 2 puncture styles for
      the depth of needle puncture and the rate of disc degeneration. OBJECTIVE: : To
      develop a simple animal model of disc degeneration. SUMMARY OF BACKGROUND DATA: :
      The study of biologically based treatments for degenerative disc disease depends
      largely on animal models. Annulus needle puncture in the lumbar spine inducing
      disc degeneration in rabbits has proven successful, but a similar method has not
      been evaluated in the tail discs of rats, even though it might produce a
      desirable model for disc repair studies. METHODS: : Two consecutive rat tail
      vertebral discs, proximal and distal to the eighth coccygeal vertebra, were
      randomized for injury and control. The disc selected for injury was punctured
      percutaneously using a 20-gauge needle with either full penetration or half
      penetration. The discs were harvested 1, 2, and 4 weeks later. Measurements
      included disc height on molybdenum target digital radiographs, biochemistry
      (water content, glycosaminoglycans, and hydroxyproline), and histology. RESULTS:
      : Needle punctures with full or half penetration caused significant disc space
      narrowing and progressive histologic changes of degeneration as early as 1 and 2
      weeks after injury, respectively. Significant decrease in glycosaminoglycan
      content was observed at 4 weeks in the half-penetration puncture discs and at 2
      and 4 weeks in discs punctured penetratively. Penetrative puncture resulted in a
      faster decrease in disc height, lower glycosaminoglycan content, and higher
      grades of histologic degeneration. The water and hydroxyproline content of the
      discs did not change appreciably. CONCLUSION: : Tail disc percutaneous needle
      puncture is a simple method for inducing disc degeneration and the rate of
      degeneration is positively related to the depth of needle puncture. This model
      still has some limitations that should be taken into consideration when results
      of disc regeneration research in this model are interpreted and extrapolated to
      human.

PMID- 18708925
TI  - Evaluation of insoluble bone gelatin as a carrier for enhancement of osteogenic
      protein-1-induced intertransverse process lumbar fusion in a rabbit model.
AB  - STUDY DESIGN: Postero-lateral lumbar fusion in a rabbit model was performed to
      compare the bone induction potential of autograft, insoluble bone gelatin (ISBG),
      osteogenic protein-1 (OP-1), and the combination of ISBG and OP-1. OBJECTIVE: To
      evaluate the efficiency of ISBG as a carrier/enhancer for OP-1 in a rabbit spinal
      fusion model. SUMMARY OF BACKGROUND DATA: OP-1 or recombinant human BMP-7 has
      been shown to be effective in inducing new bone formation in surgical
      applications such as spinal arthrodesis. However, the lack of an ideal carrier
      contributes to its associated comorbidities (e.g., uncontrolled bone growth,
      local inflammatory over-response, nonfusion) and limits its use clinically.
      METHODS: Adult New Zealand white rabbits (n = 32) underwent bilateral lumbar
      intertransverse process fusion procedures at L5 to L6 and were randomized to
      receive: (1) autograft; (2) ISBG; (3) OP-1; or (4) ISBG in combination with OP-1
      (ISBG + OP-1). Spinal fusion masses were evaluated by manual palpation,
      biomechanical testing, radiographic assessment, microcomputer tomography scanning
      and histologic examination at 6 weeks after surgery. RESULTS: Treatment of ISBG +
      OP-1 resulted in higher spinal fusion rates (7 of 7, 100%) than that of autograft
      (3 of 7, 43%), ISBG (2 of 8, 25%), and OP-1 (2 of 7, 29%) based on manual
      palpation (P < 0.01). Greater fusion rates in the ISBG + OP-1 group were also
      evidenced by radiographic examination (P < 0.01), microcomputer tomography bone
      volume analysis (P < 0.01), and biomechanical testing (P < 0.05). Histologic
      assessment demonstrated that treatment of ISBG + OP-1 induces new contiguous bone
      formation in the interval between the transverse processes which was absent in
      the other groups. CONCLUSION: In this study, ISBG + OP-1 resulted in more
      effective lumbar intertransverse process fusion than autograft, OP-1 putty or
      ISBG alone. ISBG is capable of enhancing OP-1-induced bone formation.

PMID- 18708926
TI  - Expression of apoptosis signal-regulating kinase 1 in mouse spinal cord under
      chronic mechanical compression: possible involvement of the stress-activated
      mitogen-activated protein kinase pathways in spinal cord cell apoptosis.
AB  - STUDY DESIGN: To examine apoptosis signal cascade in neurons and oligodendrocytes
      under the chronic spinal cord compression of tiptoe-walking Yoshimura (TWY)
      mouse, which is model of progressive cervical cord compression. OBJECTIVE: To
      clarify the biologic mechanisms of apoptosis, which may produce destructive
      changes in the spinal cord under chronic mechanical compression, with a resulting
      irreversible neurologic deficit. SUMMARY OF BACKGROUND DATA: The stress-activated
      mitogen-activated protein kinase pathways including ASK1 transmitted apoptosis
      signals after acute spinal cord injury. Apoptosis in acute spinal cord injury
      induced both secondary degeneration around the site of injury and chronic
      demyelination. Chronic spinal cord compression showed myelin destruction, loss of
      axons, and oligodendrocytes in white matter, and loss of neurons in gray matter.
      Apoptosis associated with chronic spinal cord compression contributes to these
      changes. However, the biologic mechanisms of apoptosis in the spinal cord under
      chronic mechanical compression remain unclear. METHODS: We examined the
      expression of phosphorylated-apoptosis signal-regulating kinase 1 (ASK1),
      phosphorylated-c-Jun N-terminal kinase (JNK), phosphorylated-p38 mitogen
      activated protein kinase (p38), and activated caspase-3 immunohistologically in
      TWY mice, an animal model of progressive cervical spinal cord compression, since
      the ASK1-JNK and -p38 signaling cascades participate in the signaling pathway
      leading to apoptosis in neural tissue and neuronal culture. RESULTS: Double
      immunohistochemistry for phosphorylated-ASK1, phosphorylated-JNK, phosphorylated
      p38, activated-caspase3, and cell-specific markers confirmed the presence of
      apoptosis signals in both neurons and oligodendrocytes in compressed spinal cord
      cells. CONCLUSION: We found that mitogen-activated protein kinase pathways
      including ASK1, JNK, and p38 were activated in destructive spinal cord under
      chronic compression.

PMID- 18708927
TI  - In vitro study on interaction between human nucleus pulposus cells and
      mesenchymal stem cells through paracrine stimulation.
AB  - STUDY DESIGN: Coculture of human nucleus pulposus (NP) cells and mesenchymal stem
      cells (MSCs) using a noncontact system. OBJECTIVE: To investigate the interaction
      between NP cells and MSCs through paracrine stimulation. SUMMARY OF BACKGROUND
      DATA: Cell-based therapies have a potential role in the treatment of
      intervertebral disc degeneration. Upregulating the viability of NP cells and
      differentiating MSCs into NP-like cells are potential alternatives to achieve
      viable cells. METHODS: Culture plates and inserts were used to coculture MSCs and
      NP cells without direct contact or exchange of cellular components. Cellular
      proliferation and RNA expression of selected genes were then evaluated after
      coculture. RESULTS: Coculturing slightly promoted the proliferation of MSCs, and
      expression of collagen I and Fas-associated death domain protein significantly
      decreased. MSCs, which initially expressed no collagen II, started to show
      collagen II expression after coculturing; the expression level was highest when
      the cells were cultured with a higher number of NP cells. On the converse,
      proliferation of NP cells significantly rose even after cocultured with a few
      MSCs. Increasing the number of cocultured MSCs did not further enhance
      proliferation of NP cells. Expression of aggrecan in the NP cells significantly
      increased when the cells were cultured with a higher number of MSCs. CONCLUSION:
      The results showed a possible mechanism of interaction between MSCs and NP cells
      mediated by secreted factors. The most significant effect on NP cells was
      enhancement of cellular proliferation when they were cocultured with even a small
      number of MSCs. To differentiate MSCs into NP-like cells with heightened collagen
      II expression, MSCs must be in an environment containing numerous NP cells.

PMID- 18708928
TI  - Biomechanical response of a lumbar intervertebral disc to manual lifting
      activities: a poroelastic finite element model study.
AB  - STUDY DESIGN: Determination of damage to a lumbar disc caused by lifting using a
      poroelastic finite element model study. OBJECTIVE: Compare the biomechanical
      response of a lumbar disc under 8 different lifting conditions and identify the
      loading conditions that produce the greatest deformations and highest stresses in
      various tissue components of the disc. SUMMARY OF BACKGROUND DATA: Lifting has
      been associated epidemiologically with back injuries and back pain complaints.
      Forces high enough to cause mechanical damage to the disc have been predicted
      using analytical methods. METHODS: Using kinematic data from series of lifts
      obtained in our laboratories and an electromyography (EMG)-driven muscle
      optimization model, representative force patterns for each of 8 lifts were
      obtained and used as input into a poroelastic finite element model. Disc tissue
      displacements and stresses were determined for all the 8 lift conditions.
      RESULTS.: Lifting the box from a maximally lateral flexed posture up to waist
      level (Task 5) produced the largest translational and rotational motions of all
      studied. This lift activity also produced maximum von Mises stresses in all disc
      components: annulus, nucleus, and endplates. The largest facet joint forces were
      also observed during lift Task 5. CONCLUSION: Asymmetric lifting involving
      lateral bending of the trunk produced large motions that might cause localized
      disc tissue injury. Stresses larger than the failure strength of the
      corresponding disc tissues were experienced during asymmetric lifting. Lifting
      that involves lateral bending of the trunk was the most hazardous type of loading
      with regard to damage to the disc.

PMID- 18708929
TI  - Does the direction of pedicle screw rotation affect the biomechanics of direct
      transverse plane vertebral derotation?
AB  - STUDY DESIGN: In vitro biomechanical investigation using human cadaveric
      vertebrae. OBJECTIVE: Evaluate the biomechanical differences in transverse plane
      vertebral body derotation maneuvers of thoracic pedicle screws in both medial and
      lateral directions. SUMMARY OF BACKGROUND DATA: Thoracic pedicle screws are
      thought to have better vertebral rotation control and better segmental scoliosis
      correction compared to hooks and wires. Little data exists regarding the
      biomechanical stability of pedicle screws when derotated in either medial or
      lateral directions. METHODS: Vertebral bodies (T4-L5) from 12 cadavers were
      instrumented with appropriate length pedicle screws while measuring insertion
      torque. Each body was anchored for independent loading in medial or lateral
      directions. Each screw was rotated around a rod using a constant length lever arm
      (30.5 cm) rigidly attached to the screw head simulating the posterior vertebral
      derotation maneuver. Yield torques (Nm) were analyzed using a one-way analysis of
      variance (P < 0.05). RESULTS: Yield torques for both directions were
      significantly related to screw insertion torque (both P < 0.01). There were no
      statistical differences in yield torque between medial (12.0 +/- 4.9 Nm) or
      lateral (11.5 +/- 5.1 Nm) directions. There were no significant differences after
      normalization for insertion torque or screw length. Tests rotating the screw tip
      laterally demonstrated structural failure in the following percentages
      (anterolateral failure = 67%, posterior element failure = 33%, additional screw
      bending = 42%). Rotation medially demonstrated structural failures in the
      following percentages (canal penetration = 51%, posterior element failure = 49%,
      additional screw bending = 44%). CONCLUSION: From these data, a surgeon
      performing a direct vertebral derotation using a 30 cm (12 in) lever would need
      to apply roughly 40 N (9 lbs) to causeanatomic failure. Adolescent patients would
      likely tolerate a greater force without bone failure given a greater bone
      density, yet, extreme caution is still recommended to prevent screw rotation
      either medially into the spinal canal or laterally into the chest.

PMID- 18708930
TI  - Comparing the clinical and radiological outcomes of pedicular transvertebral
      screw fixation of the lumbosacral spine in spondylolisthesis versus unilateral
      transforaminal lumbar interbody fusion (TLIF) with posterior fixation using
      anterior cages.
AB  - STUDY DESIGN: This study retrospectively compares the clinical and radiologic
      outcomes of unilateral transforaminal lumbar interbody fusion (TLIF) with those
      of transvertebral screw fixation of the lumbosacral spine in high-grade
      spondylolisthesis. OBJECTIVE: To examine the outcome and perioperative
      complications of unilateral TLIF and compare those results with Transvertebral
      Screw Fixation in the treatment of high-grade spondylolisthesis. SUMMARY OF
      BACKGROUND DATA: High-grade spondylolisthesis has been associated with a high
      complication and failure rate regardless of the method of treatment. We compare 2
      techniques to improve success rates. METHODS: Forty patients were divided into 2
      groups: group A, unilateral TLIF, and group B, transacral screws. The mean age
      was 33 years (range, 19-48 years), and the mean follow-up was 35 months (range,
      24-48 months). The mean grade of spondylolisthesis measured by Meyerding grading
      was 3.6 (range, 3-5). A Scoliosis Research Society outcome score was obtained on
      all patients. Fusion was determined by both radiograph and computed tomography
      scan. RESULTS: Group A: 100% fusion. The slip angle improved from 38.6 degrees
      (range, 24-78 degrees ) before surgery to 23.8 degrees (range, 12-38 degrees )
      after surgery. Group B: 95% of patients evidenced solid fusion by the 6-month
      follow-up. The slip angle, improved from 38.2 degrees (range, 22-78 degrees )
      before surgery to 23 degrees (range, 9-36 degrees ) after surgery. There was no
      significant improvement in the percentage slip or the sacral inclination in any
      of the groups. COMPLICATIONS: A: 7 unintended durotomies and 3 wound infections.
      B: 1 unintended durotomy, 1 pseudarthrosis, 2 wound infections, and 1 implant
      failure. There were no neurologic complications in any of the groups. The
      Scoliosis Research Society outcome instrument demonstrated good postoperative
      pain control, function, self-image, and satisfaction in both groups. CONCLUSION:
      No significant differences in radiologic and clinical outcome were found, in
      either group. Both procedures appear to be safe and effective surgically and
      radiographically.

PMID- 18708931
TI  - All-terrain vehicles and associated spinal injuries.
AB  - STUDY DESIGN: Case cohort. OBJECTIVE: To illuminate factors associated with all
      terrain vehicle (ATV) injuries and injury morphology. SUMMARY OF BACKGROUND DATA:
      Traditionally thought of as safe, injuries associated with ATVs can be severe and
      life threatening. In 2005 alone, the US Consumer Product Safety Commission
      estimated 136,100 injuries and 767 deaths associated with ATVs use and misuse.
      METHODS: A database of all spine related consults from one institution was
      reviewed and all patients with spine or spinal cord injuries associated with ATV
      use were identified. All pertinent demographic, clinical, and radiographic
      information were collected and analyzed. RESULTS: Thirty-six patients were
      identified from the spinal cord injury database. The male:female ratio was 11:1
      of the ATV injured patient. This is statistically different from the general
      database population, with a males representing 70% of patients (P < 0.002). The
      average ATV injured patient was 13.7 years younger than the average database
      patient (P < 0.001). The incidence of an axial compression or burst type fracture
      morphology was significantly higher in the ATV injured patient population (50%)
      compared with the database population as a whole (12%). Factors predisposing
      patients to injury on ATVs include excessive speed, use of alcohol or controlled
      substances, use of machinery after dark, and inexperience. CONCLUSION: All
      terrain vehicles (ATVs) are currently experiencing enormous popularity in the
      United States. These recreational vehicles are associated with a higher incidence
      of axial compression and burst-type fracture morphologies. In general, all
      terrain vehicles although highly dangerous leading to death or serious injury can
      be fun, enjoyable, and safe if proper regulations and safety precautions are
      implemented and followed.

PMID- 18708932
TI  - Baclofen pump implantation and spinal fusion in children: techniques and
      complications.
AB  - STUDY DESIGN: Retrospective clinical and radiographic review of complications
      related to intrathecal baclofen therapy (ITB) and posterior spine fusion (PSF) in
      patients with cerebral palsy. OBJECTIVE: To report the technical considerations
      and complications associated with ITB in patients undergoing PSF. SUMMARY OF
      BACKGROUND DATA: A common treatment for spasticity in children with cerebral
      palsy is ITB. This population also has a high incidence of severe spinal
      deformities requiring PSF. METHODS: There were 4 groups: A, 26 patients with PSF
      before ITB; B, 11 patients who underwent PSF and ITB concurrently; C, 25 patients
      with PSF after ITB; and D, the control group: 103 patients with ITB only.
      Complications and infections were tabulated from a retrospective chart review and
      ongoing surveillance data. Multiple chi analyses were used to compare the number
      of patients who experienced complications and infections among the groups. The
      operative sequence and catheter management techniques for the various scenarios
      are described in detail in the text. RESULTS: The outcome by group was as
      follows: group A had 5 catheter malfunctions and 2 infections at the pump site,
      group B had 2 catheter malfunctions, 1 hypermobile pump and 1 infection at the
      spinal site, group C had 3 catheter malfunctions, 1 infection at the pump site
      and 1 infection at the spinal site. The control group had 23 catheter
      malfunctions, 5 pump failures, 8 infections at the pump site, and 1 infection at
      the spinal site. Multiple chi analyses showed no difference in the number of
      infection or device/catheter complications among any of the groups. CONCLUSION:
      The rate of ITB therapy complications is not increased despite PSF in any order
      of the procedures. There are technical details in each situation that require
      attention. With understanding of the appropriate techniques of catheter
      management, ITB pumps can be implanted and managed without an increased
      complication rate before, during or after spinal fusion surgery.

PMID- 18708933
TI  - Hemivertebra resection for the treatment of congenital lumbarspinal scoliosis
      with lateral-posterior approach.
AB  - STUDY DESIGN: A retrospective review of patient records was conducted. OBJECTIVE:
      To evaluate the results of a lumbar hemivertebra resection and short-segment
      fusion through a lateral-posterior approach. SUMMARY OF BACKGROUND DATA: Few
      reports have been reported describing a procedure consisting of one-stage lateral
      posterior lumbar hemivertebra resection and correction of the deformity by
      segmental anterior instrumentation to date. METHODS: From 1998 to 2006, a
      consecutive series of twenty-four patients with congenital scoliosis or
      kyphoscoliosis due to a lumbar hemivertebra were managed by resection of the
      hemivertebra through a lateral-posterior approach and with the use of a short
      anterior convex-side fusion. RESULTS.: The mean age at the time of surgery was
      9.4 years (range, 6 years and 8 months-16 years and 9 months). The mean follow-up
      period was 43 months (5-94). There was a mean improvement of 61.5% in the
      segmental scoliosis curve from a mean angle of 45.2 degrees before surgery to
      17.4 degrees at the time of the latest follow-up assessment, and a mean
      improvement of 60.9% in the total main scoliosis curve from 47.6 degrees to 18.6
      degrees at the same periods. The mean final lordosis was within normal values.
      There were no major complications and no neurologic damage. CONCLUSION: Excision
      of a lumbar hemivertebra through lateral-posterior approach is safe and provides
      stable correction when combined with a short-segment fusion.

PMID- 18708934
TI  - Is rheumatoid arthritis a risk factor for a high-riding vertebral artery?
AB  - STUDY DESIGN: A retrospective comparative study on the morphologic
      characteristics of the axis in patients with or without rheumatoid arthritis
      (RA). OBJECTIVE: To compare the morphologic risk of vertebral artery (VA) injury
      during atlantoaxial transarticular screw fixation between patients with or
      without RA. SUMMARY OF BACKGROUND DATA: VA injury is a potentially serious
      complication during atlantoaxial transarticular screw fixation. Although this
      operation is frequently performed on RA patients, there have been few comparative
      studies on the morphologic risk of VA injury between RA and non-RA patients.
      METHODS: A total of 107 three-dimensional computed tomography images of the
      cervical spine including the C1-C2 complex were evaluated. Forty-seven RA
      patients and 60 non-RA patients were included in the study. The maximum
      atlantoaxial transarticular screw diameter (MSD) that could be inserted without
      breaching the cortex was measured 3-dimensionally using a computer- assisted
      navigation system. A high-riding-VA carrier was defined as a patient with either
      MSD of 4 mm or less. In RA patients, the space available for the spinal cord in
      flexion (SAC in flexion), duration of disease, RA stage, and type of disease were
      examined. RESULTS: In the RA group, 45 of 94 MSDs (47.9%) were 4 mm or less, and
      33 of 47 patients (70.2%) were high-riding-VA carriers. In the non-RA group, 11
      of 120 MSDs (9.2%) were 4 mm or less, and 9 of 60 (15.0%) patients were high
      riding-VA carriers. MSD, C3 A-P diameter, and the ratio of MSD to C3 A-P diameter
      were significantly smaller in the RA group than in the non-RA group. Multiple
      logistic regression analysis showed that SAC in flexion was a significant risk
      factor for a high-riding-VA carrier in the RA group. CONCLUSION: RA was a
      significant risk factor for the presence of a high-riding VA. When performing
      atlantoaxial transarticular screw fixation, particularly on RA patients, thorough
      preoperative evaluation of the bony architecture is of great importance to avoid
      inadvertent VA injury.

PMID- 18708935
TI  - Magnetic resonance imaging assessment of the alar ligaments in whiplash injuries:
      a case-control study.
AB  - STUDY DESIGN: Case-control study. OBJECTIVE: To use high-resolution magnetic
      resonance imaging (MRI) in assessing signal intensity areas in the alar
      ligaments. SUMMARY OF BACKGROUND DATA: Conflicting evidence exists whether areas
      of high signal intensity in the alar ligament on MRI are more frequent in
      whiplash patients than in noninjured control subjects. METHODS: A case-control
      designed study of 173 subjects included one group with persistent whiplash
      associated disorder Grade I-II after a car accident (n = 59), one with chronic
      nontraumatic neck pain (n = 57) and one group without neck pain or previous neck
      trauma (n = 57). High-resolution proton-weighted MRI in 3 planes was used. The
      images were independently evaluated by two experienced neuroradiologists who were
      blinded to patient history and group allocation. The alar ligaments were
      evaluated according to a 4-point grading scale; 0 = low signal intensity
      throughout the entire cross section area, 1 = high signal intensity in one third
      or less, 2 = high signal intensity in one-third to two thirds, and 3 = high
      signal intensity in two thirds or more of the cross section area. RESULTS: Alar
      ligament changes Grade 0 to 3 were seen in all 3 diagnostic groups. Areas of high
      signal intensity (Grade 2-3) were found in at least one alar ligament in 49% of
      the patients in the whiplash associated disorder Grade I-II group, in 33% of the
      chronic neck pain group and in 40% of the control group (chi, P = 0.22).
      CONCLUSION.: The previously reported assumption that these changes are due to a
      trauma itself is not supported by this study. The diagnostic value and the
      clinical relevance of magnetic resonance detectable areas of high intensity in
      the alar ligaments are questionable.

PMID- 18708937
TI  - Retraction.

PMID- 18708936
TI  - Greater peripheral blood flow but less bleeding with propofol versus sevoflurane
      during spine surgery: a possible physiologic model?
AB  - STUDY DESIGN: Prospective, randomized, single blind. OBJECTIVE: To compare the
      effects of sevoflurane and propofol on lumbar-paraspinal-muscles regional blood
      flow, as well as bleeding when controlled hypotension is used. SUMMARY OF
      BACKGROUND DATA: Controlled hypotension is the technique of choice to reduce
      blood loss during spine surgery, but changes in blood flow occurring to lumbar
      paraspinal muscles during controlled hypotension with propofol and sevoflurane,
      as well as the entity of bleeding, are unknown. METHODS: Blood flow was assessed
      by means of a laser Doppler flowmeter during the prehypotensive and hypotensive
      (defined as a 15% reduction of baseline mean arterial pressure) period in 28
      patients (aged 28-73 years, American Society of Anesthesiologists (ASA) I-II)
      undergoing lumbar spine surgery. Patients were randomized to receive either
      sevoflurane or propofol as main anesthetic agent to achieve hypotension. At the
      end of the surgery, blood loss was calculated and intraoperative bleeding (Visual
      Analogue Scale ranging from 0 to 100) was evaluated by the surgeon. RESULTS.:
      Peripheral Blood flow was significantly greater in the propofol group both before
      and during the hypotensive period (median values of 32.7 FU vs. 7.7 and 38.5 FU
      vs. 10.5, respectively). Despite this fact, blood loss and intraoperative
      bleeding were significantly reduced when propofol had been used (P < 0.05).
      CONCLUSION: Despite the greater blood flow when it is used, propofol causes less
      bleeding than sevoflurane during spine surgery and could be more indicated to
      produce hypotension during anesthesia. Moreover, it is possible to explain our
      findings hypothesizing a selective vasodilation of propofol (postcapillary,
      venous vasodilation), different from that of sevoflurane (precapillary,
      arteriolar vasodilation).

PMID- 18708938
TI  - Diffuse myogenin expression by immunohistochemistry is an independent marker of
      poor survival in pediatric rhabdomyosarcoma: a tissue microarray study of 71
      primary tumors including correlation with molecular phenotype.
AB  - The pathologic classification of rhabdomyosarcoma (RMS) into embryonal or
      alveolar subtype is an important prognostic factor guiding the therapeutic
      protocol chosen for an individual patient. Unfortunately, this classification is
      not always straightforward, and the diagnostic criteria are controversial in a
      subset of cases. Ancillary studies are used to aid in the classification, but
      their potential use as independent prognostic factors is rarely studied. The aim
      of this study is to identify immunohistochemical markers of potential prognostic
      significance in pediatric RMS and to correlate their expression with PAX-3/FKHR
      and PAX-7/FKHR fusion status. A single tissue microarray containing 71 paraffin
      embedded pediatric RMSs was immunostained with antibodies against p53, bcl-2, Ki
      67, CD44, myogenin, and MyoD1. The tissue microarray and whole paraffin blocks
      were studied for PAX-3/FKHR and PAX-7/FKHR gene fusions by fluorescence in situ
      hybridization and reverse transcription-polymerase chain reaction. Clinical
      follow-up data were available for each patient. Immunohistochemical staining
      results and translocation status were correlated with recurrence-free interval
      (RFI) and overall survival (OS) using the Kaplan-Meier method, the log-rank test,
      and Cox proportional hazard regression. The minimum clinical follow-up interval
      was 24 months (median follow-up=57 mo). On univariable analysis,
      immunohistochemical expression of myogenin, bcl-2, and identification of a gene
      fusion were associated with decreased 5-year RFI and 10-year OS (myogenin RFI
      P=0.0028, OS P=0.0021; bcl-2 RFI P=0.037, OS P=0.032; gene fusion RFI P=0.0001,
      OS P=0.0058). After adjustment for Intergroup Rhabdomyosarcoma Study-TNM stage,
      tumor site, age, tumor histology, and translocation status by multivariable
      analysis, only myogenin retained an independent association with RFI (P=0.034)
      and OS (P=0.0069). In this retrospective analysis, diffuse immunohistochemical
      reactivity for myogenin in RMS correlates with decreased RFI and OS, independent
      of histologic subtype, translocation status, tumor site, or stage.

PMID- 18708939
TI  - Interobserver variability between expert urologic pathologists for extraprostatic
      extension and surgical margin status in radical prostatectomy specimens.
AB  - Accurate Gleason score, pathologic stage, and surgical margin (SM) information is
      critical for the planning of post-radical prostatectomy management in patients
      with prostate cancer. Although interobserver variability for Gleason score among
      urologic pathologists has been well documented, such data for pathologic stage
      and SM assessment are limited. We report the first study to address interobserver
      variability in a group of expert pathologists concerning extraprostatic soft
      tissue (EPE) and SM interpretation for radical prostatectomy specimens. A panel
      of 3 urologic pathologists selected 6 groups of 10 slides designated as being
      positive, negative, or equivocal for either EPE or SM based on unanimous
      agreement. Twelve expert urologic pathologists, who were blinded to the panel
      diagnoses, reviewed 40x whole-slide scans and provided diagnoses for EPE and SM
      on each slide. On the basis of panel diagnoses, as the gold standard,
      specificity, sensitivity, and accuracy values were high for both EPE (87.5%,
      95.0%, and 91.2%) and SM (97.5%, 83.3%, and 90.4%). Overall kappa values for all
      60 slides were 0.74 for SM and 0.63 for EPE. The kappa values were higher for
      slides with definitive gold standard EPE (kappa=0.81) and SM (kappa=0.73)
      diagnoses when compared with the EPE (kappa=0.29) and SM (kappa=0.62) equivocal
      slides. This difference was markedly pronounced for EPE. Urologic pathologists
      show good to excellent agreement when evaluating EPE and SM. Interobserver
      variability for EPE and SM interpretation was principally related to the lack of
      a clearly definable prostatic capsule and crush/thermal artifact along the edge
      of the gland, respectively.

PMID- 18708940
TI  - Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathologic,
      immunophenotypic, and molecular study of 22 Asian cases according to WHO-EORTC
      classification.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is defined as a rare
      cytotoxic alpha/beta T-cell lymphoma characterized by primary involvement of
      subcutaneous tissue mimicking panniculitis and a predominant CD3+/CD4-/CD8+
      phenotype in 2005 World Health Organization-European Organization for Research
      and Treatment of Cancer (WHO-EORTC) classification for cutaneous lymphomas. We
      presented a detailed study of SPTL, describing clinicopathologic,
      immunophenotypic, and molecular features of 22 cases in China. Strict diagnostic
      criteria according to the WHO-EORTC definition were applied to the diagnosis of
      all SPTL cases. Besides the common features described before, unusual CD4+/CD8-
      and CD4-/CD8- T-cell phenotypes were noted in 2 of our cases, respectively. CD30
      was negative in all cases and CD56 was focally positive in 2 cases. Mortality in
      cases with angioinvasion (75%) was significantly higher than that in cases
      without angioinvasion (14.3%). Epstein-Barr virus (EBV) infection was detected in
      1 immunocompetent patient by in situ hybridization. The frequency of rearranged
      TCRB, TCRG, and TCRD genes detected by BIOMED-2 multiplex polymerase chain
      reaction tubes was 80%, 67%, and 13%, respectively, with a total clonality
      detection rate of 100%. Clinical follow-up was available in 18 patients, ranging
      from 6 to 80 months. Most patients obtained complete or partial remission after
      therapy including one accompanied with EBV infection; 5 patients died: 3 of
      disease progression, 1 of severe infection, and 1 of complications caused by
      diabetes and hypertension. We conclude that SPTL as a cytotoxic lymphoma derived
      from alpha/beta T cell has a predominant CD4-/CD8+ phenotype, but unusual
      CD4+/CD8- and CD4-/CD8- phenotypes do exist. Owing to its indolent clinical
      course and relatively high survival rate, SPTL should be differentiated from
      cutaneous gamma/delta T-cell lymphoma. EBV is generally absent in SPTL but can
      rarely be detected especially in Asian population. Angioinvasion is a poor
      prognostic factor in SPTL.

PMID- 18708941
TI  - Solitary peripheral ciliated glandular papillomas of the lung: a report of 3
      cases.
AB  - We report 3 cases of solitary papillomas located in peripheral regions of the
      lung that are extremely rare in the literature. The patients were 75-year-old and
      72-year-old men and a 53-year-old woman. One patient complained of recurrent
      hemoptysis. The other 2 had no symptoms, but abnormal nodular shadows were
      revealed by chest radiographs during a health check. The maximum diameters of the
      tumors were 1.0, 1.4, and 1.1 cm, respectively. The 3 tumors gave almost the same
      histologic findings. Papillomatous fronds lined by a stratified columnar
      epithelium were seen in the lumens of peripheral bronchi, bronchioles, or
      alveoli. The stratified columnar epithelium consisted of ciliated, mucous, and
      basal cells. The neoplastic epithelium extended to the alveolar region and showed
      a similar appearance to bronchioloalveolar or papillary type adenocarcinomas. For
      differential diagnosis, it is noteworthy that endobronchiolar papillomatous
      fronds constantly exist and spreading along alveolar walls is limited in adjacent
      alveoli in peripheral papillomas. The presence of ciliated cells and basal cells
      is considered an important finding to suggest benign character of the lesion.

PMID- 18708942
TI  - Significance of central perivenulitis in pediatric liver transplantation.
AB  - Central perivenulitis (CP) encompasses dropout of zone 3 hepatocytes, red blood
      cell extravasation, and perivenular mononuclear inflammation. In the liver
      transplant setting, CP can occur in isolation or it can occur in association with
      portal-based disease such as acute cellular rejection (PB-ACR). Some CP is also
      thought to be a manifestation of chronic rejection, particularly when accompanied
      by zone 3 fibrosis. Prior studies of CP in pediatric liver allografts have been
      hampered by lack of protocol biopsies and low rates of histologic follow-up. We
      studied 62 consecutive liver allografts from 55 pediatric patients (age: < or =18
      y) who underwent transplant from the years 1995 to 2007. Forty-nine allografts
      (79%) had > or =1 year of histologic follow-up, 32 (52%) > or =3 years, and 24
      (39%) > or =5 years. We reviewed a total of 445 allograft biopsies (mean: 7.2 per
      allograft) obtained at 2 days to 11 years; 213 (48%) of these were protocol
      biopsies. Seven explanted livers that were removed during the course of
      retransplantation for graft failure in this group were also reviewed. All
      specimens were scored for the following features: (1) CP (mild, moderate, and
      severe), (2) portal ACR (mild, moderate, and severe), (3) zone 3 fibrosis
      (mild=perivenular or severe=bridging), and (4) ductopenia. CP was present in 120
      (27%) of 445 biopsies, including 73 with CP+PB-ACR, 16 with CP within 1 month of
      PB-ACR, 27 with isolated CP, 3 with CP+de-novo autoimmune hepatitis, and 1 with
      CP+Epstein-Barr virus infection. Overall, CP was observed on at least 1 occasion
      in 41 (66%) allografts. It was not associated with any specific liver function
      test abnormality or pattern of liver function test abnormalities, it was not
      associated with vascular compromise as judged by Doppler ultrasound examinations,
      and it was not related to type of immunosuppression. CP overall was equally
      prevalent in the early (< or =3 mo) and late (>3 mo) post-transplant periods, but
      isolated CP increased in the late period. On follow-up, 6 (15%) of 41 allografts
      with CP developed ductopenic chronic rejection (4 requiring retransplantation)
      and 10 (25%) developed zone 3-based fibrosis without ductopenia (2 severe, 8
      mild). In contrast, none of the 21 allografts without CP developed chronic
      rejection (P=0.09) and none had zone 3-based fibrosis on their last biopsy
      (P<0.001). All patients who developed ductopenia had 1 or more episodes of CP+PB
      ACR. In contrast, isolated CP [seen in 17 (27%) allografts on at least 1
      occasion] was associated with zone 3-based fibrosis in 50%, but did not lead to
      ductopenic chronic rejection. These results underscore the high frequency of CP
      in pediatric liver transplantation, occurring in 27% of all allograft biopsies
      and 66% of allografts overall. CP is most common in conjunction with portal ACR,
      where it carries a significant risk for the development of zone 3 fibrosis and a
      trend toward the development of ductopenic chronic rejection.

PMID- 18708944
TI  - Knowledge of attitude toward experience and satisfaction with electroconvulsive
      therapy in a sample of Iranian patients.
AB  - Despite the wide consensus over the safety and efficacy of electroconvulsive
      therapy (ECT), it still faces negative publicity and unfavorable attitudes of
      patients and families. Little is known about how the experience with ECT affects
      the patients' and their families' attitude toward it. The aim of this study was
      to examine a sample of Iranian patients and their families regarding their
      experience with ECT and to compare their knowledge and attitude toward ECT before
      and after this experience and their satisfaction with it. We surveyed 22 patients
      with major depressive disorder about to undergo ECT and 1 family member of each
      patient for their knowledge and attitude toward ECT and then surveyed them again
      after the trial of ECT to compare those variables while assessing their
      experience and satisfaction with ECT. Patients were rated using the Hamilton
      Depression Rating Scale and Mini-Mental Status Examination before and after the
      treatment. We found that, before ECT, family members had a more favorable
      attitude toward ECT than patients, but after ECT, the patients' attitude changed
      more positively compared with their families. Both patients and their families
      had a poor knowledge of ECT before the ECT trial, but their total knowledge
      increased afterward, although not in the areas of indications and therapeutic
      effects. The majority of patients and their families found ECT to be beneficial
      and were satisfied with it. Satisfaction with ECT was independent of treatment
      outcome. There was a high rate of perceived coercion to consent to ECT. Attention
      should be paid toward educating patients and their families about the ECT
      process, indications, risks, safety, and effects as well as informing them about
      their freedom of choice and right to refuse.

PMID- 18708943
TI  - Toward individualized post-electroconvulsive therapy care: piloting the Symptom
      Titrated, Algorithm-Based Longitudinal ECT (STABLE) intervention.
AB  - OBJECTIVES: Effective strategies to prolong remission after electroconvulsive
      therapy (ECT) are urgently needed. Fixed schedules for continuation ECT (C-ECT)
      cannot adapt to early signs of impending relapse. Symptom-Titrated, Algorithm
      Based Longitudinal ECT (STABLE) is proposed as a novel patient-focused approach
      to individualize the ECT schedule. In STABLE, the ECT schedule adapts to symptom
      fluctuations to prevent overtreatment of those who do not need it and to
      recapture response in those who might have otherwise relapsed with a rigid dosing
      schedule. Here we back-test STABLE to optimize the algorithm for subsequent
      testing in a prospective trial. METHODS: Three variations of the STABLE
      algorithm, differing in cutoff points to trigger or withhold additional ECT, were
      back-tested in a data set of 89 patients randomized to the C-ECT arm in the CORE
      (Consortium for Research on ECT) Study comparing C-ECT with combination
      pharmacotherapy. RESULTS: The selected algorithm identified 100% of patients who
      ultimately relapsed as requiring additional ECT at an average of 2.2 weeks before
      relapse, while exposing 20% of sustained remitters to additional ECT. Other
      variations either failed to capture impending relapse or exposed an unacceptably
      large percentage of patients to potentially unnecessary ECT. CONCLUSIONS: This
      patient-focused approach to relapse prevention is an attempt to provide the first
      operationalized guidance to the field regarding how to conduct C-ECT. The
      effectiveness of this approach should be tested in a randomized controlled trial.

PMID- 18708945
TI  - Electroconvulsive treatment for a patient with psychotic depression and inclusion
      body myositis.
AB  - A patient with inclusion body myositis (IBM) and psychotic depression required
      inpatient psychiatric care. The patient's mental and physical health continued to
      deteriorate despite maximal treatment with medication. After careful
      consideration and psychiatric, neurological, and anesthetic review,
      electroconvulsive therapy was initiated. We present, what is to our knowledge,
      the first documented case of a patient with inclusion body myositis requiring a
      course of electroconvulsive therapy for psychotic depression.

PMID- 18708946
TI  - Electroconvulsive therapy practice in Poland.
AB  - OBJECTIVE: The aim of the study reported herein was to determine the
      characteristics of electroconvulsive therapy (ECT) practice in Poland. METHOD: A
      20-item questionnaire was sent to all Polish inpatient psychiatric facilities
      including all academic centers, general hospital psychiatric wards and
      psychiatric institutions. RESULTS: Each of the 58 departments (100%) replied by
      mail or by phone. A total of 25 departments indicated the use of ECT, but only in
      20 departments was it administered regularly. Altogether, 435 patients (0.79% of
      all inpatients) were treated with ECT in Poland during 2005. The main indications
      of ECT were affective disorders. Bitemporal electrode placement was used twice or
      3 times a week in each setting. Anesthesia was usually induced either with
      thiopental or propofol. The wide variations in the investigations for pre-ECT
      evaluation reflect the lack of a generally accepted ECT protocol in Poland.
      CONCLUSION: The rate of ECT use in Poland is among the lowest in the Central-East
      European region, which raises the possibility that many patients who otherwise
      would greatly benefit from ECT do not receive this treatment.

PMID- 18708947
TI  - Examination of the effect of education about electroconvulsive therapy on nursing
      practice and patient satisfaction.
AB  - INTRODUCTION: Electroconvulsive therapy (ECT) procedures require the work of a
      multidisciplinary team that includes an anesthesiologist, a psychiatrist, and a
      treatment nurse. Electroconvulsive therapy is treated like a minor surgical
      procedure that requires preoperative preparation and postoperative care. AIM:
      This research was conducted as a quasi-experimental study for the purpose of
      evaluating the effect of education about ECT given to nurses who work on a
      psychiatric ward. SAMPLE: The research pretest sample was composed of 52 ECT
      procedures in which nurses participated in managing that were conducted between
      April and October 2006 on the psychiatric ward of Dokuz Eylul University
      Hospital. The posttest sample was composed of 52 ECT procedures in which nurses
      participated in managing that were conducted between January and March 2007 on
      the same psychiatric ward. DATA COLLECTION TOOL: The observation form for the
      determination of nursing care in ECT and satisfaction form, which were developed
      by the researcher from expert opinion, were used for data collection. Data
      obtained were analyzed using the test for significance between 2 means. RESULTS:
      The nurses included in the research received a total score of 4 for nursing care
      in ECT procedure before education and X = 11.5 after education. The difference in
      the mean scores for nursing care in ECT procedure before and after education was
      found to be statistically significant (P < 0.05). The mean score for patient
      satisfaction with nursing care in ECT procedure before education was X = 2.5 and
      that after education was X = 4.1. The difference between the 2 means was found to
      be statistically significant. CONCLUSIONS: Education given to nurses about ECT
      improved nursing practice and increased patient satisfaction. For this reason, it
      is recommended that nursing care in ECT continuing education be planned and given
      at regular intervals.

PMID- 18708948
TI  - Race as a variable in pharmacogenomics science: from empirical ethics to
      publication standards.

PMID- 18708949
TI  - Functional characterization of 23 allelic variants of thiopurine S
      methyltransferase gene (TPMT*2 - *24).
AB  - OBJECTIVE: Thiopurine S-methyltransferase (TPMT) is an enzyme responsible for the
      detoxification of the widely used thiopurine drugs. TPMT is genetically
      polymorphic and is associated with large interindividual variations in thiopurine
      drug toxicity and therapeutic efficacy. In this study, we performed an in-vitro
      analysis of TPMT variant alleles, namely, TPMT*2, *3A, *3B, *3C, *5, *6, *7, *8,
      *9, *10, *11, *12, *13, *14, *16, *17, *18, *19, *20, *21, *22, *23, and *24.
      METHODS: The wild-type TPMT proteins, TPMT.1 and 23 variants were heterologously
      expressed in COS-7 cells, and the kinetic parameters Km, Vmax, and intrinsic
      clearance (Vmax/Km) of 6-thioguanine S-methylation were determined. RESULTS: The
      expression levels of TPMT.2, TPMT.3A, TPMT.5, TPMT.12, TPMT.14, and TPMT.22 were
      considerably lower than that of TPMT.1 (P<0.005), and that of TPMT.18 was
      slightly reduced (P<0.05). The kinetic parameters of TPMT.3A, TPMT.3B, TPMT.5,
      TPMT.14, TPMT.18, TPMT.21, and TPMT.22 could not be accurately established
      because of no activity in 6-thioguanine S-methylation. The Vmax/Km values of
      TPMT.2, TPMT.7, TPMT.17, and TPMT.24 were displayed less than 10% of the wild
      type. CONCLUSION: This functional analysis with respect to TPMT variants could
      provide useful information for individualization of thiopurine drugs therapy.

PMID- 18708951
TI  - Epidemiological, clinical, laboratory findings, and outcomes of disseminated
      tuberculosis in Tehran, Iran.
AB  - BACKGROUND: Disseminated tuberculosis (TB) accounts for 1 to 3% of all TB cases.
      This retrospective study reviews the clinical, radiological, laboratory findings
      and outcome in patients with disseminated tuberculosis in an endemic area.
      METHODS: Medical records were reviewed for patients with disseminated TB admitted
      to two tertiary centers in Tehran, Iran between 1999 and 2006. RESULTS: Fifty
      patients were found to have disseminated TB. A miliary pattern was documented in
      the chest x-ray of 34 patients. Hematologic abnormalities including anemia,
      leukopenia, and thrombocytopenia were frequently observed. Death occurred in nine
      of the cases. The mortality rate was significantly higher in diabetic patients,
      injection drug users, and patients with hematologic abnormalities; however,
      steroid usage and human immunodeficiency virus infection were not significantly
      associated with a higher mortality rate. Clinical improvement occurred in 41
      patients following treatment. CONCLUSION: Disseminated TB could have different
      manifestations. Hematologic abnormalities are common and are considered poor
      prognostic signs in these patients.

PMID- 18708952
TI  - Stenting as an alternative to open repair in traumatic superficial femoral artery
      injuries.
AB  - Lower limb ischemia may occur when a superficial femoral artery (SFA) is injured
      in blunt or penetrating trauma. Surgical repair of the injured artery can be
      challenging and time-consuming when there is an associated fracture. Two cases of
      traumatic SFA injury treated with endovascular stent grafting are described.

PMID- 18708953
TI  - Recurring tracheal papillomatosis treated with cryosurgery.
AB  - Cryosurgery has proven effective in managing malignant tracheobronchial tumors,
      yet its role in benign lesions is not well established. A case of isolated
      tracheal papillomas recurring 15 years following laser surgery is reported.
      Cryosurgery allowed improvement in symptoms and adequate control of the
      papillomas.

PMID- 18708954
TI  - Patient's page. Menopause.

PMID- 18708956
TI  - Value of myocardial regional perfusion on long-term function in collateral
      dependent myocardium.
AB  - BACKGROUND: Collateral circulation is considered key for left ventricular (LV)
      function recovery in patients with chronic total occlusion (CTO). However, there
      are conflicting reports about the influence of collaterals on LV recovery after
      revascularization. METHODS: Echocardiographic assessment of regional myocardial
      perfusion, wall motion score (WMS), and left ventricular ejection fraction (LVEF)
      were performed in patients with angiographically visible collateral circulation
      of grades 2 and 3. RESULTS: The WMS and LVEF of group B (with presence of
      myocardial regional perfusion) were significantly improved at one month and six
      months compared to those of group A (with absence of myocardial regional
      perfusion). The correlation between myocardial regional blood flow and changes in
      WMS and LVEF was significant at 6 months in patients with angiographically
      visible collateral circulation of grade 2 and 3. Similar correlations were
      observed on myocardial contrast echocardiography (MCE) score index. CONCLUSION:
      Myocardial function recovery in patients with CTO is determined by myocardial
      regional perfusion. MCE has important value for prognosis and risk stratification
      in patients with CTO undergoing cardiac catheterization.

PMID- 18708957
TI  - Protean manifestations of metabolic syndrome.

PMID- 18708962
TI  - Overlooked aspartame-induced hypertension.

PMID- 18708963
TI  - Ischemic colitis, an unusual complication of colonoscopy.

PMID- 18708964
TI  - Hydrocortisone in severe sepsis: time to accept the null hypothesis?

PMID- 18708965
TI  - Long-term survival after glioblastoma multiforme.

PMID- 18708966
TI  - Hypertrophic pulmonary osteoarthropathy disappearance despite lung cancer
      relapse.

PMID- 18708967
TI  - The nose knows cancer recurrence.

PMID- 18708968
TI  - Serious cardioembolic stroke resulting from an overlooked left ventricular
      noncompaction.

PMID- 18708969
TI  - Prevalence of vitamin D deficiency and insufficiency in northeast Tennessee.
AB  - BACKGROUND: Vitamin D deficiency is increasingly being recognized as a highly
      prevalent and undertreated problem. This study was conducted to determine the
      prevalence of vitamin D deficiency/insufficiency in hospitalized adults in
      northeast Tennessee. METHODS: A prospective cohort study was conducted on 99
      inpatients admitted to an internal medicine teaching service from July through
      October 2006 at a single private hospital in Johnson City, Tennessee. A single
      measurement of 25-hydroxyvitamin D was performed on all patients. RESULTS: Of the
      99 patients, 53% were vitamin D deficient or insufficient (30% deficient with a
      level of <20 ng/mL and 23% insufficient with a level between 20-29.9 ng/mL). The
      highest frequency of deficiency was in females <50 years. CONCLUSION: Vitamin D
      deficiency is highly prevalent in all age groups and in both females and males in
      this population. Clinicians should consider measuring the vitamin D level of all
      inpatients on a routine basis.

PMID- 18708970
TI  - IgA deposits along glomerular basement membranes in rapidly progressive
      glomerulonephritis.
AB  - This case presents a rare type of crescentic glomerulonephritis characterized as
      IgA deposits predominantly along the glomerular basement membranes (GBM). The
      patient clinically manifested with rapidly progressive glomerulonephritis (RPGN)
      without pulmonary hemorrhage or vasculitis-related systematic symptoms. No
      positive results were found on antinuclear antibody (ANA), antineutrophil
      cytoplasmic antibody (ANCA), or anti-GBM antibody detection. Therapy with pulse
      methylprednisolone and intravenous cyclophosphamide was less effective. This case
      does not belong to the present three categories of crescentic glomerulonephritis
      based on the clinical characteristics, serum test, immunofluorescence, and
      electron microscopic findings.

PMID- 18708971
TI  - The impact of drug samples on prescribing to the uninsured.
AB  - OBJECTIVE: To determine whether drug samples are associated with physicians
      prescribing fewer generic, less costly medications. METHODS: We conducted a
      retrospective study at a large university-affiliated internal medicine practice
      containing over 70 physicians. Using a pharmacy database, we identified all
      prescriptions written to uninsured or Medicaid patients that belonged to one of
      four classes of chronic medications. For the 9 months before and after the clinic
      closed its drug sample closet, we calculated the percentage of medications
      prescribed as generics and the mean cost of a 30-day supply of a prescription.
      RESULTS: Of 8911 prescriptions, 1973 met inclusion criteria. For uninsured
      patients, the percentage of medications prescribed as generics rose from 12% to
      30% after the clinic closed its drug sample closet (P = 0.004). By consecutive
      three month periods, the percentage of prescribed generic medications rose
      steadily to a maximum of 40% (P < 0.001). For Medicaid patients, there was no
      significant change in generic prescribing (63% generic with samples versus 65%
      generic without samples, P = 0.42). Two factors were associated with generic
      prescribing in logistic regression: the absence of drug samples (OR 4.54, 95% CI
      1.37-15.0) and the prescriber being an attending physician (OR 5.26, 95% CI 2.24
      12.4). There was no statistically significant change in cost for either group.
      CONCLUSIONS: Physicians were three times more likely to prescribe generic
      medications to uninsured patients after drug samples were removed from the
      office. Drug samples may paradoxically lead to higher costs if physicians with
      access to samples prescribe more brand-name only drugs.

PMID- 18708972
TI  - Multiorgan failure caused by intravascular lymphoma: a highly rare and malignant
      hemopathy mimicking multisystemic disease.
AB  - This manuscript describing a case of intravascular lymphoma, displays the
      difficulties underlying its diagnosis. We emphasize that intravascular lymphoma
      should be considered in patients with multisystemic manifestations without
      obvious etiology. Despite the heterogeneous presentation of this lymphoma, some
      clinical and biological investigations should prevail clinicians to do tissue
      biopsy which is required to make the diagnosis.

PMID- 18708973
TI  - Rationale for fixed-dose combination therapy to reach lower blood pressure goals.
AB  - Expert committees in the United States and Europe formulated their currently
      recommended target blood pressures of <140/90 mm Hg or <130/80 mm Hg in persons
      with diabetes, chronic kidney disease, or coronary artery disease based on the
      totality of clinical data available at the time. However, accumulating evidence
      indicates that increased risk for cardiovascular and renal complications of
      hypertension may begin at a threshold of 115/75 mm Hg, suggesting that benefit
      from treatment may occur when blood pressure targets are lower than those
      currently recommended. Combination therapy with two or more agents having
      complementary mechanisms of action is the most effective method for achieving
      strict blood pressure goals in high-risk patients. Several clinical trials are
      under way to further determine the risks and benefits of lowering blood pressure
      beyond the currently recommended threshold.

PMID- 18708974
TI  - What is the impact of free drug samples on patients?

PMID- 18708975
TI  - Treatment of hypersexual behavior with oral estrogen in an autistic male.
AB  - Hypersexual behavior can be exhibited by patients with autism. Several
      medications have been used in hypersexual paraphiliac male and elderly patient
      populations, including antiandrogens, estrogen, gonadotropin-releasing hormone
      analogues, and selective serotonin reuptake inhibitors. Due to limited research
      in autistic patients exhibiting hypersexuality, physicians must base their
      medication selection on outcomes seen in patients with other conditions.

PMID- 18708976
TI  - A mask and many faces: hypokalemic periodic paralysis.

PMID- 18708977
TI  - Major pulmonary embolism and hemodynamic stability from shunting through a patent
      foramen ovale.
AB  - While the combination of a patent foramen ovale (PFO) and thromboembolic disease
      is thought to portend increased morbidity and mortality, PFO presence in the
      setting of major pulmonary embolism (PE) may serve as a means to rescue patients
      from immediate hemodynamic collapse and death. We present two patients with major
      pulmonary embolism and right-to-left shunting consistent with PFO as seen on
      transthoracic echocardiography. In the setting of major PE, PFO may prevent acute
      right ventricular failure by acting as a 'pop-off' valve, alleviating increased
      ventricular pressures; but concomitantly portend deleterious effects in the form
      of paradoxical embolism and intractable hypoxemia.

PMID- 18708978
TI  - Rituximab therapy for refractory thrombotic thrombocytopenic purpura and
      autoimmune-mediated thrombocytopenia in systemic lupus erythematosus.
AB  - Thrombotic thrombocytopenic purpura (TTP) rarely occurs in the setting of
      systemic lupus erythematosus (SLE); when it does occur it has a high mortality
      rate and is refractory to conventional treatment. No clear treatment guidelines
      exist when refractory TTP occurs in the setting of SLE. A 24-year-old male
      patient presented with TTP in the setting of SLE that was refractory to
      conventional treatment but responded to rituximab.

PMID- 18708979
TI  - Apparently persistent weakness after recurrent hypokalemic paralysis: a tale of
      two disorders.
AB  - A 19-year-old woman presented with recurrent hypokalemic paralysis, followed by
      apparently persistent symptoms due to coexisting osteomalacia. Distal renal
      tubular acidosis type 1 (dRTA1) linked the metabolic abnormalities and occurred
      as an extraglandular feature of Sjogren syndrome (SS). This case highlights the
      fact that in the setting of recurrent hypokalemia, apparently progressive
      weakness should be distinguished from primary hypokalemic paralysis and evaluated
      for dRTA1, as the metabolic alterations are potentially treatable. Further dRTA1
      may precede the occurrence of sicca syndrome in SS.

PMID- 18708980
TI  - Current concepts in the postoperative care of the rhinoplasty patient.
AB  - This is a systematic review of the available literature and our own personal
      experience regarding the optimal management of the rhinoplasty patient. The
      routine utilization of nasal splinting, casting and perioperative antibiotics is
      supported. The management of a number of common early complications is also
      discussed. Meticulous technique based on sound structural principles and coupled
      with preoperative planning and attention to wound care will result in a favorable
      outcome in most individuals undergoing rhinoplasty.

PMID- 18708981
TI  - Esophageal Crohn disease.

PMID- 18708982
TI  - Benefits of percutaneous coronary revascularization in patients with adequately
      collateralized chronic total occlusions.

PMID- 18708983
TI  - Crohn disease of the esophagus: a review of the literature.
AB  - Esophageal Crohn disease is a difficult disease both to diagnose and treat. The
      diagnosis is made in patients with other extraintestinal manifestations of Crohn
      disease in whom other esophageal pathology has been ruled out. This often
      requires integration of clinical, endoscopic, radiographic, and histologic
      findings. Despite its relative rarity, it does cause severe symptoms that are
      difficult to treat. Treatment requires careful integration of medical,
      endoscopic, and surgical techniques. This review aims to discuss the significant
      literature regarding diagnosis and treatment of this important manifestation of
      inflammatory bowel disease. There is additional discussion of the literature
      regarding the efficacy of newer medical and endoscopic therapies, including
      biologic agents and removable polymer stents.

PMID- 18708984
TI  - Optimal blood pressure control in high-risk groups: are the guidelines letting us
      down?

PMID- 18708985
TI  - An unusual case of knee pain: pseudogout and Abiotrophia defectiva infection.
AB  - A 90-year-old man was diagnosed with monoarticular arthritis due to pseudogout
      and Abiotrophia defectiva infection. A. defectiva is recognized as a cause of
      endocarditis, but is rarely described in septic arthritis. To our knowledge, this
      is one of the few case reports of septic arthritis due to this organism, and the
      first in association with pseudogout. This report supports the routine culture of
      synovial fluid and is further evidence for the role of A. defectiva in septic
      arthritis.

PMID- 18708986
TI  - Coexistence of hepatocellular carcinoma (HCC) and c-Kit negative gastrointestinal
      stromal tumor (GIST): a case report.
AB  - A past history of sporadic solid cancers is disclosed in 10% of gastrointestinal
      stromal tumor (GIST) patients. Simultaneous occurrence with other malignancies is
      encountered in 14 to 16%, but the synchronous occurrence of GIST and
      hepatocellular carcinoma (HCC) has been reported only once in the English
      literature. An 81-year-old male patient is presented with a preoperatively known
      HCC, in whom a synchronous small nodular omental GIST adjacent to the lesser
      curvature of the stomach was incidentally discovered. When a GIST is encountered,
      a thorough intraoperative investigation of the abdominal cavity currently remains
      the only reliable method for detection of a possible coexisting malignancy.

PMID- 18708987
TI  - Metabolic syndrome as a risk factor for nonalcoholic fatty liver disease.
AB  - BACKGROUND: Metabolic syndrome has been linked to nonalcoholic fatty liver
      disease (NAFLD). OBJECTIVES: The purpose of the current study was to evaluate
      metabolic syndrome as a risk factor for NAFLD in Taiwanese adults. METHODS: A
      cross-sectional study was conducted in which 876 subjects were enrolled. The
      diagnosis of NAFLD was made by abdominal ultrasonography. The Asia-Pacific
      modification of the National Cholesterol Education Program (NCEP) Adult Treatment
      Panel (ATP) III guidelines was used to establish the diagnosis of metabolic
      syndrome. RESULTS: NAFLD was diagnosed in 373 (42.6%) of the study population.
      Metabolic syndrome was diagnosed in 202 (23.1%) of the study population, and it
      was independently associated with NAFLD (odds ratio [OR] = 2.37; P < 0.001).
      Among the components of metabolic syndrome, hypertriglyceridemia (OR = 2.24; P <
      0.001), hyperglycemia (OR = 2.23; P = 0.001), increased waist circumference (OR =
      1.76; P = 0.013), and the diagnostic components of metabolic syndrome were
      independently associated with NAFLD. CONCLUSION: Metabolic syndrome and some of
      its diagnostic components are independent risk factors for NAFLD.

PMID- 18708988
TI  - Pain relief with intraarticular or medial branch nerve blocks in patients with
      positive lumbar facet joint SPECT imaging: a 12-week outcome study.
AB  - BACKGROUND: Single-photon emission computed tomography (SPECT) is useful in
      identifying patients who may respond to lumbar facet injections. There are two
      methods for performing lumbar facet joint injections: intraarticular and medial
      branch nerve blocks. A consensus has yet to be reached among physicians as to
      which method is the most effective. The purpose of this study was to compare the
      effectiveness of intraarticular and medial branch nerve blocks in SPECT-positive
      lumbar facet joint patients with nonradicular lower back pain. METHOD: This study
      was a prospective, double-blinded outcome study of 12 weeks' duration. Forty-six
      male (26) and female patients (20) between the ages of 18 and 55 (mean 39.3
      years) with nonradicular lower back pain who were lumbar facet joint SPECT
      positive were studied. No patient was included in this study if magnetic
      resonance imaging evidence of a lumbar disc herniation was present. Patients were
      randomly assigned by computer to have intraarticular (group I) or medial branch
      nerve blocks (group II) with lidocaine and triamcinolone, with 23 patients in
      each group. Outcome measurements assessed the Numeric Pain Intensity Scores (NPIS
      0-10) and the Oswestry Disability Index scores (ODI 0-50). RESULTS: There were no
      differences in demographics between the two groups. The percentage of pain relief
      (61%) and the percentage of disability (53%) reduction were significantly greater
      (P <0.05) in group I when compared to group II (26% and 31% respectively).
      CONCLUSIONS: Intraarticular lumbar facet joint injections are more effective than
      medial branch nerve blocks in SPECT-positive patients.

PMID- 18708989
TI  - A cross-sectional study of HIV and tuberculosis coinfection cases in mainland
      China.
AB  - BACKGROUND: The prevalence of HIV/AIDS and tuberculosis (TB) within mainland
      China is unprecedented and the convergence of these two infectious diseases is
      increasingly and significantly endangering human health for socioeconomic
      development. To date, the clinical manifestations, laboratory presentation, and
      epidemiologic features of HIV/TB coinfection cases in mainland China have not
      been described in detail. To assess the incidence, clinical characteristics and
      outcome of coinfection with HIV and TB, we conducted a cross-sectional study of
      coinfected cases reported from nine domestic hospitals throughout mainland China.
      METHOD: During the 3-year survey period from January 2003 to December 2005, all
      patients were followed regularly. Medical records were reviewed, a standardized
      questionnaire was administered, and clinical databases were analyzed. RESULTS: A
      total of 241 cases (183 male, 58 female) with pulmonary TB, extrapulmonary TB, or
      both, accounted for 9.5%, 21.6%, and 18.7% of cases, respectively. Among the 241
      reported cases of HIV/TB coinfection, 76.8% had CD4 cell counts 200/mm3 and 58.5%
      were 100/mm3. Treatments for TB and HIV were provided to patients and mortality
      attributable to coinfection was reported for 15.8% of the cases. CONCLUSIONS: The
      clinical characteristics of HIV/TB coinfection varied among the 241 cases studied
      with pulmonary TB predominating. Immune function among most patients was
      suppressed based on reduced CD4+ T cell counts. HIV/TB coinfection was related to
      high mortality even when HAART and/or drug therapy for TB was provided.
      Additional sensitive techniques are needed to improve the diagnosis of HIV/TB
      coinfection.

PMID- 18708990
TI  - Prescribing patterns and the use of therapeutic drug monitoring of psychotropic
      medication in a psychiatric high-security unit.
AB  - The aim of this study was to investigate the use of psychotropic medication and
      therapeutic drug monitoring in a high-security psychiatric unit and to compare
      the doses and serum concentrations both with the recommended intervals and with
      the doses and serum concentrations in a control group. One hundred thirty-two
      patients were admitted in the period from January 2000 to December 2005. All
      available samples were used when comparing serum concentrations and doses with
      the recommended ranges. For the comparison of doses and serum concentration-to
      dose (C:D) ratios with the control group only 1 sample from each patient was
      used. A total of 459 analyses of 27 different drugs in samples from 8 women and
      73 men were included. The median number of therapeutic drug monitoring analyses
      per patient was 4 (range 1-29). Thirty-seven of the 81 patients (46%) used 2 or
      more antipsychotics at the same time. Clozapine, lamotrigine, olanzapine,
      quetiapine, ziprasidone, and zuclopenthixol were often given in doses above the
      recommended. The serum levels were frequently above those recommended for
      clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zuclopenthixol.
      The serum levels were significantly higher in the study group than in the control
      group for clozapine, lamotrigine, quetiapine, and zuclopenthixol. The given dose
      was significantly higher in the study group than in the control group for
      clozapine, lamotrigine and zuclopenthixol. The C:D ratio was significantly lower
      in the study group than in the control group for olanzapine but higher for
      quetiapine. The non-evidence based practice of high-dose polypharmacy with
      several antipsychotics is widely used in this unit. The use of higher doses in
      the study group than in the control group was not due to differences in
      metabolism or adherence to treatment between the 2 groups. The frequent use of
      therapeutic drug monitoring did not seem to have a great impact on the prescribed
      doses.

PMID- 18708991
TI  - ABCB1 polymorphisms influence steady-state plasma levels of 9-hydroxyrisperidone
      and risperidone active moiety.
AB  - Risperidone is metabolized to its active metabolite, 9-hydroxyrisperidone, mainly
      by the cytochrome P450 enzymes CYP2D6 and 3A4. Its antipsychotic effect is
      assumed to be related to the active moiety, that is, the sum of risperidone and 9
      hydroxyrisperidone. Both risperidone and 9-hydroxyrisperidone are substrates of P
      glycoprotein (P-gp), a transport protein involved in drug absorption,
      distribution, and elimination. The aim of the present study was to evaluate the
      influence of polymorphisms in genes encoding CYP3A5 and P-gp (ABCB1) on the
      steady-state plasma levels of risperidone, 9-hydroxyrisperidone, and the active
      moiety, taking CYP2D6 genotype status into account. Forty-six white patients with
      schizophrenia treated with risperidone (1-10 mg/d) in monotherapy for 4-6 weeks
      were genotyped, and their plasma concentrations of risperidone and 9
      hydroxyrisperidone were measured. Dose-corrected plasma concentrations (C/D) of
      risperidone, 9-hydroxyrisperidone, and active moiety showed up to 68-, 9-, and 10
      fold interindividual variation, respectively. Six patients carried 1 CYP3A5*1
      allele and therefore were likely to express the CYP3A5 enzyme. The CYP3A5
      genotype did not influence risperidone, 9-hydroxyrisperidone, or active moiety
      C/Ds. The CYP2D6 genotype in these 46 patients was again associated with
      risperidone C/D (P = 0.001) but not with 9-hydroxyrisperidone C/D or active
      moiety C/D, as previously shown by our group in 37 of these patients. Patients
      homozygous for the ABCB1 3435T/2677T/1236T haplotype had significantly lower C/Ds
      of 9-hydroxyrisperidone (P = 0.026) and active moiety (P = 0.028) than patients
      carrying other ABCB1 genotypes. In conclusion, our results confirmed the
      significant effect of CYP2D6 genotype on the steady-state plasma levels of
      risperidone and showed that ABCB1 polymorphisms have a moderate effect on those
      of 9-hydroxyrisperidone and the active moiety.

PMID- 18708992
TI  - Impact of changing from cyclosporine to tacrolimus on pharmacokinetics of
      mycophenolic acid in renal transplant recipients with diabetes.
AB  - The rate of mycophenolic acid (MPA) absorption after oral administration of
      mycophenolate mofetil (MMF) is delayed in patients with diabetes. Cyclosporine
      (CsA) decreases MPA exposure by inhibiting enterohepatic recirculation of MPA/MPA
      glucuronide, and tacrolimus (TRL) may alter the rate and extent of MPA absorption
      due to its prokinetic properties especially in patients with diabetic
      gastroparesis. This study evaluated the effect of changing from CsA to TRL on
      pharmacokinetics of MPA in stable renal transplant recipients with long-standing
      diabetes. Eight patients were switched from a stable dose of CsA to TRL while
      taking MMF 1 g twice daily. The 12-hour steady-state total plasma concentration
      time profiles of MPA and MPA glucuronide were obtained after oral administration
      of MMF on 2 occasions: first while taking CsA and second after changing to TRL.
      Pharmacokinetic parameters of MPA were calculated by the noncompartmental method.
      Changing from CsA to TRL resulted in significantly increased MPA exposure (area
      under the concentration-time curve from 0 to 12 hours, AUC0-12) by 46 +/- 32% (P
      = 0.012) and MPA predose concentration (C0) by 121 +/- 67% (P = 0.008). The
      magnitude of change in MPA exposure did not correlate well with MPA-C0 or CsA
      trough concentration. Switching to TRL had minimal impact on peak concentration
      of MPA (15.0 +/- 6.9 mg/L with CsA versus 16.1 +/- 9.7 mg/L with TRL, P = 0.773)
      and time to reach the peak concentration (1.0 +/- 0.4 hours with CsA versus 1.2
      +/- 0.8 hours with TRL, P = 0.461). Highly variable and unpredictable changes in
      MPA exposure among renal transplant patients with diabetes do not support a
      strategy of preemptively adjusting MMF dose when switching calcineurin inhibitors
      in this population.

PMID- 18708993
TI  - Development and validation of a highly sensitive liquid chromatography/mass
      spectrometry method for simultaneous quantification of lenalidomide and
      flavopiridol in human plasma.
AB  - Lenalidomide, an immunomodulatory agent, and flavopiridol, a broad cyclin
      dependent kinase inhibitor, are active therapies for clinical use in genomic high
      risk chronic lymphocytic leukemia. A high-performance liquid chromatographic
      assay with tandem mass spectrometric detection has been developed to
      simultaneously quantify lenalidomide and flavopiridol in human and mouse plasma
      to facilitate their combined clinical development. Samples were prepared by
      liquid-liquid extraction with acetonitrile (ACN)-containing internal standard,
      genistein, followed by evaporation of solvent and reconstitution in 95/5 H2O/ACN.
      Lenalidomide and internal standard were separated by reversed-phase liquid
      chromatography on a C-18 column using a gradient of H2O and ACN, each with 0.1%
      formic acid. Atmospheric pressure chemical ionization in positive ion mode with
      single reaction monitoring on a triple quadrupole mass spectrometer was applied
      to detect transitions of lenalidomide (260.06 > 149.10) and flavopiridol (402.09
      > 341.02). Lower limits of quantification of lenalidomide and flavopiridol were 1
      and 0.3 nM, respectively. Recoveries of lenalidomide and flavopiridol from human
      plasma ranged from 99% to 116% throughout their linear ranges. Within- and
      between-run precision and accuracy of replicate samples were all less than 15%.
      This is the most sensitive analytical method reported to date for both
      lenalidomide and flavopiridol. This sensitivity will enable late terminal phase
      concentration measurements and accurate pharmacokinetic parameter estimation in a
      planned clinical trial with lenalidomide and flavopiridol in patients with
      chronic lymphocytic leukemia.

PMID- 18708994
TI  - Effects of uremic serum and uremic toxins on hepatic uptake of digoxin.
AB  - Not only the renal clearance but also the hepatic clearance of drugs varies with
      the progression of renal failure. The aim of this study was to investigate the
      effects of human uremic serum and various uremic toxins on the hepatic uptake of
      digoxin (DX), a drug mainly excreted into bile in patients with severe renal
      failure, using isolated rat and human hepatocytes as model systems. Uremic serum
      inhibited the uptake of DX into rat hepatocytes in a concentration-dependent
      manner, whereas normal serum did not affect the uptake. In addition, 3-carboxy-4
      methyl-5-propyl-2-furanpropanoic acid (CMPF), hippuric acid, indole-3-acetic
      acid, indoxyl sulfate, and p-cresol (PC) concentration dependently inhibited the
      uptake. CMPF and PC at the concentration of 400 microM, which is within the
      plasma concentration range attained in patients with renal failure, inhibited the
      uptake of DX into rat hepatocytes by 27% and 23%, respectively. In human
      hepatocytes, 10% uremic serum, 400 microM CMPF, and 400 microM PC inhibited the
      uptake of DX by 23.3%, 23.4%, and 28.2%, respectively. In conclusion, our results
      suggest that hepatic uptake of DX is likely to be inhibited by uremic toxins,
      such as CMPF and PC, present in the serum of patients with renal failure.

PMID- 18708995
TI  - Bridging the I.V. access gap with midline catheters.

PMID- 18708996
TI  - Chronic kidney disease: a hidden epidemic.
AB  - Chronic kidney disease (CKD) is increasingly recognized as a global public health
      problem. Now, there is convincing evidence that CKD can be detected using simple
      laboratory tests and that treatment can prevent or delay the complications of
      decreased kidney function, slow the progression of kidney disease and reduce the
      risk of cardiovascular disease (CVD). Two simple tests can detect almost all CKD.
      The estimated GFR and a urine albumin-to-creatinine ratio provide adequate
      testing. We do not have data on the prevalence of CKD in adults in the Republic
      of Macedonia. There has been an increase of End Stage Renal Disease and Renal
      Replacement Therapy in our country. In 2002 we had 1056 patients on RRT compared
      with 1216 in 2005. The nephrologists of Macedonia held a symposium devoted to the
      World Kidney Day on March 13, 2008, at the Macedonian Academy of Sciences and
      Arts in Skopje. One of the most important messages was that there is an urgent
      need for a screening programme for the detection of CKD in the Republic of
      Macedonia. Health authorities, nephrologists and general physicians should
      collaborate together on the detection of CKD.

PMID- 18708997
TI  - Pre-operative staging of gastric carcinoma.
AB  - This study is a prospective clinical investigation that includes 195 patients
      (pts), of whom 64 were diagnosed with gastric cancer and endosonographically
      determined operability. Endosonography is not used in the primary detection and
      diagnosis of gastric cancer, but as a supplementary method that, besides the
      basic detection of the presence or absence of a tumour, gives additional
      information about the extent of the neoplasm. For this investigation the patients
      were divided into 3 groups. The first group of 58 pts (30%) were those with
      benign gastric lesions, 18 pts with polyps and 40pts with gastric ulcers
      respectively. The second groups of 64 pts (32.5%) consisted of those with gastric
      cancer. According to the endosonographic findings this group consisted of 2
      subgroups: 45 operable patients and 19 inoperable patients with gastric cancers.
      The third group consisted of 73 pts (37.5%) who were without any changes in the
      gastric wall. The endosonographic findings in the first subgroup that underwent
      surgery were correlated with the final intraoperative stage and pathohistology,
      and in the second subgroup they were compared with the operative finding during
      the palliation procedure and the final diagnosis of the additional investigation.
      All these qualities make this method useful for the diagnosis, control and follow
      up of the findings in all of the stadiums of the disease including the post
      operative period.

PMID- 18708998
TI  - Total parenteral nutrition in treatment of patients with inflammatory bowel
      disease.
AB  - Patients with Inflammatory Bowel Disease (IBD) are exposed to nutritional risk.
      Malnutrition in Crohn's Disease (CD) and to a somewhat lesser in Ulcerative
      Colitis (UC) is very frequent. Depending on the severity of the disease, weight
      loss has been reported in 65% to 76% of those with CD and in 18% to 62% of those
      with UC. The role of Total Parenteral Nutrition (TPN) is essential in very severe
      cases where enteral nutrition is not tolerated or standard drug therapy is not
      effective. Nutritional therapy is important for the correction of nutritional
      deficiency, especially in cases where elective surgical treatment is required.
      This study examined the effects of preoperative TPN administration in patients
      with IBD. Since 1990, 29 pts, 13 (44.8%) male and 16 (55.2%) female with severe
      IBD; 16 (55.2%) with UC and 13 (44.8%) with CD were treated with TPN in our
      department in the preoperative period. Evaluation of this group was compared with
      a group which was not treated with TPN preoperatively: 61 pts, 34 (55.7%) male,
      27 (44.3%) female; 50 (82%) with CD, 11 (18%) with UC. Evaluation of this group
      was compared with the group of patients who were subjected to surgical procedure
      without prior TPN administration, in total a number of 61, of whom 34 (55.7%)
      were male and 27 (44.3%) female patients. In this group, the number of patients
      with CD and UC was 50 (82%) and 11(18%) respectively. During the course of the
      study, the following parameters were examined: Body mass index (BMI), Disease
      Activity Index (CDAI/AI), laboratory parameters and the number of hospital days.
      The parameters were analysed before the surgical intervention, and one week and
      six months after the surgical intervention. The duration of the application of
      TPN was 12.5 +/- 5 days. The analysis of these parameters has shown that there is
      no statistically significant difference in the number of hospital days in both
      groups, which was 18.9 +/- 8.9 in the intervention group and 18.9 +/- 6.5 days in
      the control group, p = 0.9808, but analysis of the Disease Activity (CDAI/AI) has
      shown that patients who were on TPN were in a more severe stage of the disease.
      In the TPN treated group of patients none, 0 pts (0%), of the pts had no Index of
      Activity, 1.7 pts (24.1%) had Index 2 and 22 (75.9%) had Index 3. In the other
      group 3 pts (4.9%) had Index 1; 39 pts (63.9%) had Index 2 and 19 pts (31.2%) had
      Index of Activity 3. During the monitoring period of six months the activity of
      the disease was lower in patients treated with TPN. The BMI in the group of
      patients treated with TPN was lower in both sexes. It was lower than 18.4 in 7
      males and 5 females; between 18.4 and 19.9 in 2 males and 4 females; between 19.9
      and 25 in 3 males and 6 females; between 25 and 19.9 in 1 male and 1 female;
      there were no pts with BMI higher than 29.9. In the control non-TPN group, 5
      males and 3 females had BMI < or = 18.4; 2 males and 5 females had between 18.4
      and 19.9; 23 males and 13 females had between 19.9 and 25; 3 males and 5 females
      had between 25 and 29.9 and 1 male and 1 female had BMI higher than 29.9. The BMI
      had an increasing trend in the postoperative period in both groups. The
      laboratory parameters that we examined were: number of erythrocytes and
      sedimentation, number of leukocytes, haemoglobin levels, total number of
      lymphocytes, albumin level, C-reactive protein, orosomucoid, electrolytes;
      sodium, potassium, calcium and serum iron, the enzymes (AP, AST and ALT); level
      of bilirubin and urea and creatinine. The results were analysed using the Tukey
      honest significant difference test (HSD), ANOVA and Student t-test. Statistically
      significant differences were observed between preoperative and postoperative
      period in both groups. The intergroup comparison showed significant differences
      in the level of albumin, AST, ALT and bilirubin.

PMID- 18708999
TI  - Trends in acute leukaemia incidence in adults in the Republic of Macedonia (1993
      2003)--a descriptive epidemiological study.
AB  - OBJECTIVE: To analyse trends in incidence rates of acute leukaemia in patients
      aged 15 and over admitted to hospital. DESIGN: A descriptive epidemiological
      study. SETTING: University teaching hospital, Haematology Clinic, Skopje.
      RESULTS: The crude incidence rates of acute leukaemia in adults during this
      period increased substantially (p for overall trend < 0.001). The lowest crude
      incidence rates (CIR) were observed in 1996 (CIR = 1.64/100 000; 95% Confidence
      Interval CI = 1.1-2.4), while the highest were noted in 2003 (CIR = 3.76/100 000;
      95% CI = 2.9-4.8). In 1993 the sex ratio of the incidence rates (males to
      females) was Rate Ratio (RR) = 2.23, while as of 2001 the association between
      sexes disappeared (RR = 1). The trend in males was not significant (p = 0.160),
      while in females it showed a monotonic increase that was highly significant (p <
      0.001). CONCLUSIONS: During a short period of time (11 years) we have noted an
      increase in the incidence rates of acute leukaemia in our population aged 15
      years and above. The study suggests that this could be due to increased risk in
      females, and in adults over 40 years. In addition, according to the census
      results in 1994 and 2002 the proportion of people aged 65 and above increased by
      30.5% implying that this demographic change could account for part of the
      relative increase in the incidence rates of acute leukaemia. Further analytic
      studies are needed to address the possible causes of these changes. What is
      already known on this topic: The risk of acute leukaemia increases by age and it
      is higher in males than in females. WHAT THIS STUDY ADDS: The incidence rates are
      equal between the sexes; the increase in risk of acute leukemia in females could
      be due to environmental risk factor.

PMID- 18709000
TI  - Virulence factors and antibiotic resistance in Enterococcus faecalis isolated
      from urine samples.
AB  - Haemolysin, enterococcal surface protein (Esp), aggregation substance and
      gelatinase are some markers that have been proposed as possible enterococci
      virulence factors. The aim of this study was to detect the presence of
      haemolysin, gelatinase and enterococcal surface protein in enterococci isolated
      from urine and to determine their susceptibility to antimicrobial agents. A total
      of 50 strains of Enterococcus faecalis isolated from urine samples was examined.
      UTI agar (Oxoid) was used for the isolation and identification of the strains as
      Enterococcus spp. The differentiation of the species was done by the Vitek
      automated system (GPI-card). Haemolysin production was detected phenotypically on
      Columbia CNA agar as a zone of beta haemolysis around the streak. Production of
      gelatinase was determined as a clear halo around the colonies on tripticase soy
      agar supplemented with 1.5% skim milk. Esp was proved by detection of the esp
      gene using PCR after DNA extraction. Antibiotic sensitivity to ampicillin,
      ceftriaxone, vancomycin, nitrofurantoin and ciprofloxacin was examined by the
      agar diffusion method. In 16 Enterococcus faecalis strains (32%) all the
      virulence factors were present. Two factors were found in 19 (38%) strains and
      only one in 11 strains. There were only 4 strains without any virulence factor.
      Esp was the most frequently determined factor (in 38 isolates). All the strains
      were susceptible to vancomycin and nitrofurantoin; 12 isolates were resistant to
      ampicillin, 17 to ceftriaxone and 14 to ciprofloxacin. No relationship was found
      between virulence factors and resistance to an antibiotic.

PMID- 18709001
TI  - C-reactive protein in patients with normal perfusion and mild to moderate
      perfusion defects who have undergone myocardial perfusion imaging with 99m-Tc
      sestamibi gated spect.
AB  - High-sensitivity C-reactive protein (CRP) has been extensively used in recent
      years to assess cardiovascular risk more thoroughly. A significant association
      between elevated CRP, a prevalence of coronary artery disease (CAD) and adverse
      cardiac events has been found. Stress myocardial SPECT perfusion imaging (MPI) is
      an accurate noninvasive technique for detecting CAD. The aim of our study was to
      find out if there are any differences in the CRP levels between patients with
      normal myocardial perfusion and mild to moderate perfusion defects, detected with
      99m-Tc sestamibi gated SPECT MPI. We prospectively studied 127 patients (79 men,
      48 women) suspected of having CAD or with previously confirmed CAD, who were
      referred for MPI. According to the findings of the stress study, they were
      divided into two groups: with normal/ near normal myocardial perfusion (n = 85)
      and with a mild to moderate perfusion defect (n = 42). Levels of CRP in the
      former group were significantly lower (2.7 mg/L vs. 4.2 mg/L, p = 0.01). There
      were significantly more men (78.6% vs. 54%, p = 0.000*) and smokers (26% vs. 15%,
      p = 0.003), also the rates of PCI were significantly higher (36% vs. 15%, p =
      0.006) in patients with mild to moderate perfusion defects. The two groups did
      not differ significantly in age, type of stress, presence of most risk factors
      for CAD, previous myocardial infarction and CABG. The results of our study have
      shown that patients with mild to moderate perfusion defects on stress myocardial
      perfusion SPECT imaging have significantly higher levels of C-reactive protein,
      compared to those with normal/near normal myocardial perfusion.

PMID- 18709002
TI  - Ambiguous allele combinations at group level of HLA-A, -C, and -B genes in
      Macedonian population using reverse line strip typing method.
AB  - The aim of this study was to investigate the occurrence of ambiguous allele
      combinations at the allele group level of HLA-A, -C and -B loci in the Macedonian
      population. The DNA samples of 214 healthy unrelated Macedonian volunteers were
      obtained from our DNA Bank. HLA typing was performed using the IHWG-RLS method
      (Reverse Line Strip, Roche Molecular Systems, USA) consisting of PCR
      amplification of exon 2 and 3 of HLA-A, -B and -C genes, followed by
      hybridization. The statistical analysis of the observed ambiguity frequency was
      performed by using the Arleqin Software. At the HLA-A locus only one ambiguous
      allele combination at the allele group level in 214 samples was observed with a
      frequency of 0.467% (1/214 = 0.467%). A total of 6 different HLA-C ambiguous
      allele combinations at the allele group level in twelve samples with a frequency
      of 5.607% (12/214 = 5.607%) and 11 different for HLA-B locus in nineteen samples
      with a frequency of 8.879% (19/214 = 8.879%) were observed in 214 samples. In
      conclusion we can say that analysis of the frequency of allele ambiguities
      revealed that the ambiguities involved some of the most common alleles in our
      population, obviating the need to introduce ambiguity resolution
      technique(s)/strategies in the HLA laboratory.

PMID- 18709003
TI  - Methodological and organizational aspects of newborn screening for congenital
      hypothyroidism in Macedonia.
AB  - Congenital hypothyroidism (CH) is the most common preventable cause of mental
      retardation. Early diagnosis and treatment are crucial to the prevention of
      severe intellectual deficit. Neonatal screening in a blood spot from the heel of
      the newborn between the 2nd and 5th day after birth and determination of thyroid
      stimulation hormone (TSH) level by fluoroimmunoassay (DELFIA method) is the
      commonly used approach for the timely detection and therapy of congenital
      hypothyroidism. Over the period April 2002 - December 2004 results of 27,782
      samples were analysed. They were obtained from 5 hospitals in the Republic of
      Macedonia (Obstetrics and Gynaecology Clinic, Clinical Centre, Skopje; Cair
      Obstetrics and Gynaecology Hospital, Mala Bogorodica Hospital and hospitals
      within the cities of Bitola and Prilep). Over the period January 2005 - December
      2007 the analysis of 50,732 samples covered all obstetrics hospitals in
      Macedonia. For the first period analysed (April 2002 - December 2004) we
      evaluated the sensitivity and specificity of the biochemical method applied for
      neonatal screening for CH. In our study TSH was assayed by DELFIA fluorometric
      kits. The cut-off value in our laboratory was 15 mU/L. We compared coverage,
      timeliness of programme indicators (age at sampling, recall and treatment
      initiation, timing of specimen delivery and laboratory results) and specimen
      quality with international standards. Recall rate, sensitivity, specificity,
      positive predictive values and relative incidence rate for CH were calculated.
      The established method was deemed highly sensitive and highly specific. During
      the period of analysis in our study, 28 cases were detected or an incidence rate
      of 1 : 2,804 was calculated. Treatment was initiated on the 13th day on average
      (between the 5th and 35th day).

PMID- 18709004
TI  - Doppler ultrasonography: a tool for nephrologists--single centre experience.
AB  - Colour Doppler duplex ultrasonography (CDUS) has allowed noninvasive assessment
      of alterations of vascular perfusion showing general perfusion in colour. Since
      1996, ultrasound examination by a duplex Doppler apparatus has been performed
      with an HDI 3000, ATL machine. We have retrospectively evaluated all patients
      (pts) with colour Doppler duplex examination for the last three years. Resistive
      indexes (RIs) are measured in each kidney using the existing software
      capabilities of the scanner. A total of 2581 CDUS examinations were performed
      over the past three years; in 2005 - 883 pts, in 2006 - 908 pts and in 2007 - 790
      pts. Most of these examinations were on transplant pts. In 98 cases we examinated
      chronic rejection reactions, in 58 cases acute rejection and in 38 cases we
      postulated renal artery stenosis or thrombosis. We used CDUS to determine whether
      the RI can be used as a predictor in pts with Diabetic Nephropathy; in 108 cases
      we found an increased RI > 0.68. There is a positive correlation between the RI
      and the severity of arteriolosclerosis in the majority of pts, 331, where we
      found nephroarteriolosclerosis (RI > 0.64). In 52 cases renal artery stenosis was
      suspected (0.04 differences between RI on right and left renal artery). Acute
      renal failure was suspected in 53 cases. According to neoplasms, pathological,
      marked increased vascularization was noticed in 34 cases suspected for renal
      carcinoma, in 46 cases suspected of testicular tumours, 19 cases suspected of
      prostate neoplasm and in 32 cases suspected of tumours in other localizations. In
      combination with patient history, clinical and laboratory examination CDUS
      provides very useful information in accomplishing the diagnosis.

PMID- 18709005
TI  - Clinical importance of insulin resistance after renal transplantation in patients
      on triple immunosuppressive therapy with cyclosporine, corticosteroids and
      mycophenolate mofetil.
AB  - INTRODUCTION: Post-transplant diabetes mellitus and impaired glucose tolerance
      are confirmed complications after solid organ transplantation associated with the
      use of glucocorticoids and calcinuerin inhibitors in maintenance
      immunosuppression. Insulin resistance (IR) is also an independent factor for
      cardiovascular morbidity and mortality among renal allograft patients. The aim of
      our work was to investigate the clinical importance of elevated IR in renal
      transplant recipients on standard triple-drug immunosuppression in correlation
      with immunosuppressive therapy and certain independent factors such as body mass
      index (BMI), time after transplantation, lipid disorders, etc. METHODS: 36
      allograft pts with different periods after transplantation without previous
      glucose disorders were included in the study. An oral glucose tolerance test
      (OGTT) was made to distinguish pts with or without glucose disorders. The basal
      values of glucose (G) and insulin (I) were used to calculate indexes of IR and
      beta-cell function according to the homeostasis equations. Impaired fasting
      glucose (IFG), impairred glucose tolerance (IGT), impaired post prandial
      hyperglycemia (IPPH) and diabetes mellitus (DM) were also analysed. RESULTS: The
      mean value of the IR index was 2.57 +/- 1.20. It was elevated in 31 pts (86%) The
      IR showed a positive correlation with: I0 (p < 0.01), I2 (p < 0.05), beta cell
      function (p < 0.05) and CsA (p < 0.01). The fasting I, G, and BMI were shown as
      independent risk factors for IR (p < 0.01, p < 0.01, and p < 0.05 respectively).
      There were 12 pts with different glucose disorders (IFG, IGT, DM) and 24 pts
      without. The pts with glucose disorders showed an elevated IR index (91%) more
      frequently compared with (41.67%) decreased beta-cell function. CONCLUSION: IR is
      frequent among renal recipients with and without glucose disorders. IR is an
      independent risk factor for atherogenesis. Higher CsA trough levels are
      assotiated with higher Insulin values and indexes of IR. The defect in insulin
      action is more a prominent mechanism in post-transplant glucose disorders than
      the impaired insulin secretion.

PMID- 18709006
TI  - Lipid profile and concentration of ApoA-1 and ApoB-100 in patients with end-stage
      renal disease treated by repeated haemodialysis.
AB  - Lipid metabolism disorders in patients with end-stage renal disease, particularly
      in patients with nephrotic syndrome, were described by Dr Bright as long ago as
      1827 [1]. It is known that patients with end-stage renal disease (ESRD) display a
      clinical picture of early accelerated (premature) atherosclerosis with severe
      cardiovascular and cerebral complications that are very often present even at a
      relatively early age compared with the general population. Today, it is
      considered that uraemic dyslipidaemia has persisted for many years before chronic
      dialysis treatment begins and presents a basic risk factor for an early start of
      the atherogenesic processes. That is why an analysis of apolipoprotein and lipid
      abnormalities as well as their etiopathogenetic mechanism in patients diseased
      with ESRD treated with repeated haemodialysis in the initiation phase of dialysis
      (the first 6 months), can clearly contribute to taking timely preventive measures
      (dietetic, healing) by which the frequency of apolipoprotein and lipid
      abnormalities will be decreased, which, at the same time, will result in reducing
      the processes of early atherosclerosis with all its complications in ESRD
      patients [2]. Disorders of apolipoprotein metabolism are considered as one of the
      most important factors for early atherosclerosis in patients with ESRD [3].

PMID- 18709007
TI  - Slow progression of chronic kidney disease and what it is associated with.
AB  - INTRODUCTION: The risk factors for CKD include diabetes, hypertension, smoking,
      systemic inflammation, obesity, proteinuria, dislipidaemia and anaemia, as well
      as gender, age, ethnic minority status and positive family history. By screening
      and adequate treatment of modifiable risk factors we are able to prevent or delay
      the progression of the disease. AIM: The aim of the study was to assess the risk
      factors associated with rapid progression of CKD and to see what factors are
      protective of slow progression. METHODS: The study is retrospective. The medical
      charts of 116 patients with CKD who had been followed up for several years at the
      Outpatient Department of the Nephrology Clinic in Skopje were analysed. Patient
      age ranged from 19 to 78 years. The patients were divided into two groups: fast
      progressors - group I (n = 82; GFR decline > 0.1 ml/min/month) and slow
      progressors - group II (n = 34; GFR decline = or < 0.1 ml/min/month) with an
      average follow-up time of 55 months. Patients with diabetic nephropathy were
      excluded from the study because they are known to be fast progressors. The
      following variables were analysed: underlying cause of CKD, gender, age, time of
      follow-up, initial GFR (calculated creatinine clearance according to the Cockroft
      and Gault formula), final GFR, systolic and diastolic blood pressure, mean and
      pulse blood pressure, haemoglobin, cholesterol and 24h protein excretion rate.
      Progression of CKD was assessed by linear regression analysis of the mean monthly
      decrease of calculated creatinine clearance (delta CCcr). RESULTS: There was no
      statistically significant difference between fast and slow progressors regarding
      their systolic, diastolic, mean and pulse arterial blood pressure. With regard to
      the other risk factors, it appeared that progressors are significantly younger
      (50.50 vs 59.20; p = 0.001, more anaemic Hb-116.68 g/l vs 123.27; p = 0.0036),
      more proteinuric (1.46 g/d vs 0.76; p = 0.003) and have higher diastolic blood
      pressure (92.25 mmHg vs 84.75 mmHg; p = 0.005) compared to non-progressors. There
      was no statistical difference between the groups in terms of gender (p = 0.451).
      Regarding renal diagnosis, there was a statistically significant difference in
      progression among the four diagnostic groups, p = 0.00208. Chronic
      glomerulonephritis (GN) was associated with significantly faster progression
      (delta KKK = -0.5525 ml/min/mo) compared to interstitial
      nephritis/nephrosclerosis (IN/NS) (delta KKK = -0.2542 ml/min/mo), p = 0.03918,
      and compared to unknown renal disease (Unkn) (delta KKK = -0.1487 ml/min/mo), p =
      0.0245. Polycystic kidney disease (PKD) had faster progression (delta KKK = 
      0.5704 ml/min/mo) compared to IN/NS, p = 0.04340 and compared to Unkn, p =
      0.0251. CONCLUSION: Timely recognition of risk factors for CKD progression and
      their treatment by correction of high blood pressure, reduction of proteinuria,
      correction of anaemia and dyslipidaemia (to lower cardiovascular risk) may retard
      progression of CKD to end-stage renal disease, thus delaying the need for renal
      replacement therapy.

PMID- 18709008
TI  - Cardiac memory (t-wave memory) after ablation of posteroseptal accessory pathway.
AB  - BACKGROUND: Cardiac memory is a phenomenon characterized by transient T-wave
      abnormalities occurring during normal sinus rhythm, after a period of altered
      ventricular depolarization, where the T-wave vector has the same direction as the
      vector of the previously altered QRS complex (T-wave inversion). It is a form of
      electrical remodelling of the ventricular, where the T-wave follows ("remembers")
      a previously altered QRS vector. METHODS AND RESULTS: Over a 5-year period (2002
      2006), 525 consecutive patients underwent electrophysiological study. One hundred
      and one patients underwent ablation of the atrioventricular reentry tachycardia
      (AVRT) with an accessory pathway (AP). Forty-two of them were without delta wave
      on the electrocardiogram (concealed accessory pathway), and 58 patients had an
      open form of accessory pathways, with delta wave on EKG (Wolff-Parkinson-White
      syndrome) and only one patient had an accessory pathway between the right atrium
      and right bundle branch (Mahaim form). According to the location of the accessory
      pathway, 17 patients (29.3 %) had an accessory pathway in the right posteroseptal
      region. There was the highest percentage of the appearance of inversion of the T
      wave in patients with this position of accessory pathway. T-wave changes were
      followed in the frontal plane (leads II, III, and aVF). Electrocardiogram (ECG)
      signs of cardiac memory were present in 16 of 17 (94.1 %) patients within one day
      after the ablation. The post-ablation T-wave vector had the same direction as the
      vector of the pre-excited QRS complex (and delta wave) creating inferior T-wave
      inversions. There was no correlation between the number or duration of energy
      applications and the extent of cardiac memory post ablation. A majority (90% of
      cases) of ECGs recorded 3 months after the procedure showed complete or almost
      complete normalization. None of the patients with T-wave inversion after ablation
      had a recurrence of preexcitation or tachycardia during the follow-up period of
      12 +/- 4 months. CONCLUSIONS: T-wave inversion in leads II, III and aVF with the
      disappearance of the delta wave after ablation of the accessory pathway in
      patients with Wolff-Parkinson-White syndrome (accessory pathway in the right
      posteroseptal region of the heart), is the most powerful marker of successful
      ablation.

PMID- 18709009
TI  - The advantages of the application of amnion membrane in the treatment of burns.
AB  - A crucial and important factor for successful treatment of burns is the early
      covering of the burned area with skin substitutes. The covering of the burn
      requires material that restores the epidermal function and integrates itself into
      the process of healing. Biological dressings are the golden standard for the
      temporary covering of burns. All biological skin substitutes are susceptible to
      early graft reaction and the only exception is the amnion membrane. The
      importance of the amnion membrane as a biological dressing for burns amounts to:
      a barrier to bacterial colonization, hastens the epithelisation, and control of
      water loss. Amnioplasty is a method of application of amnion membrane on the
      recipient site. In this comparative study, 60 patients with dermal and sub-dermal
      burns were included. Research was made on an examination group of 30 patients
      with burns where the method of amnioplasty was applied, and for this amnion
      membrane conserved in 76% alcohol was used. The control group was made up of 30
      patients with burns treated conventionally, and standard methods for the local
      treatment of burns were applied: exposition, occlusive dressing and initial
      excision with skin grafting. Pathohistological and microbiological analyses of
      the bioptical material were made. The degree of the burns was determined through
      a pathohistological analysis of the bioptical material taken the third day, and
      in some of the subjects where re-epithelialization was determined on the seventh
      day, the further re-epithelialization was observed clinically. Pathohistological
      examination enabled discrimination between bacterial colonization and the
      invasive bacterial infection. Furthermore, the type of bacterial colonization and
      infection was determined, which was confirmed with microbiological analysis. The
      analysis of the results from the microbiological and pathohistological researches
      of the bioptical material according to the bacterial colonization and infection
      showed that, although between the examined and the control group there was no
      statistically important difference, the value of p = 0.067 is close to the
      statistically important value of p < 0.05. The results of the pathohistological
      examination of the bioptical material taken the seventh day and analysed
      according to the re-epithelialization showed that there was a significant
      difference between the two groups of p < 0.035. It should be mentioned that,
      although according to the microbiological examinations of the bioptical material
      a statistically significant difference was not achieved, clinical significance
      was achieved. The obtained significance of p < 0.035 compared to the re
      epithelialization in both groups approved the application of the method of
      amnioplasty. The histological analysis of the bioptical material not only
      determines the degree of the burns specifically, but facilitates the choice of
      method for further treatment, observes the speed of the re-epithelialization and
      plays an important part in the correct diagnosis and the early start of the
      specific therapy, important in preventing sepsis. The application of amnion
      membrane as a biological dressing speeds the re-epithelialization and prevents
      invasive bacterial infection. Pathohistological examination of the burns is
      recommended to be established as a standard method in clinical practice.

PMID- 18709010
TI  - Our experience in treatment of pressure ulcers by using local cutaneous flaps.
AB  - Pressure ulcers appear in very ill patients and in states of prolonged
      immobilization. They are quite frequent in intensive care units and in paraplegic
      individuals. The expenses for their sanation are huge, due to the complicity of
      the long-lasting treatment. Shallow and superficial pressure ulcers are treated
      conservatively. Deep ones, with expressive underlying bone prominence in which no
      regression is on-going, are better to be treated operatively, if possible. Thus
      the hospitalisation period and the need for frequent dressings are shortened,
      preventing enormous scars (sanatio per secundam intentionem of the wound) and the
      risk of subsequent infection. What is also important for the treatment of the
      prime disease is that the patient can rehabilitate earlier. There are many
      methods of excision of the ulcer, ablation of the bone prominence and coverage of
      the defect with different types of flaps afterwards. Although muscle flaps can be
      utilized, we assume that their use additionally influences the general condition
      of the patient (malnutrition and anaemia always co-exist). Thus we find our way
      of treatment less traumatising and better, if pliable, for decubital ulcers. The
      objective of the study was to evaluate the clinical results after an operative
      treatment of deep decubital ulcers (III and IV grade) with local dermal flaps and
      to promote the method of their closure. We paid special attention to ablation of
      the bone prominence. We used local pivotal adipose-cutaneous flaps in order to
      cover the cleansed tissue defect. The types of flaps employed were unilateral and
      bilateral rotation flaps, transposition and bipedicular flaps. Our series covered
      23 patients who were operated on in the last 10 years, of whom 16 (69.6%) had a
      spinal cord injury (paraplegic). Pressure ulcers in the sacral region dominated
      with 12 cases (52.2%). The operative techniques that we used were as follows:
      unilateral rotation flaps (in 7 patients), bilateral rotation flap (in 1
      patient), transposition flaps (in 10 patients), bipedicular flaps (in 2
      patients), free skin Thiersch auto-transplant (in 2 patients) and direct closure
      of the defect (in 1 patient). The results advocate the justification of these
      ways of treatment of pressure ulcers, with few early and late complications.

PMID- 18709011
TI  - Hip reduction in cerebral palsy with soft tissue operative procedures.
AB  - Hip reduction in cerebral palsy patients with a soft tissue procedure was
      analysed during operative procedure. Eleven patients with unilateral dislocation
      of the hip and a quadriplegic form of cerebral palsy underwent soft tissue
      operation on the hips. Tenotomy of the adductor and flexor muscles of the hip was
      performed. The contralateral hip sustained only tenotomy of the adductor muscles.
      The average age of the patient study group was 8.5 and the follow-up period was 4
      years. In all patients, repositionings of the hip were achieved and stabilization
      was maintained postoperatively at the regular outpatient follow-up. The range of
      extension and abduction motion were increased postoperatively compared to the
      preoperative range of motion. Retention of the hip was maintained within 20
      degrees of abduction. Tenotomy of the adductor and flexor muscles enables hip
      reduction without opening the joint capsule in quadriplegic cerebral palsy
      patients. The hip became painless and the improvement in the hygiene was evident.

PMID- 18709012
TI  - EEG spectra in pediatric research and practice.
AB  - After a short review of the developmental characteristics, integrality and
      complex structure of the EEG spectrum, some original clinical experiences with
      the diagnosis and treatment of related rhythm abnormalities in children and
      adolescents are presented. In particular, the approach and results concerning
      ADHD, OCD and dehydration disorders are discussed. In addition, the environmental
      effects on neuronal oscillations due to lead pollution and electromagnetic
      radiation are considered.

PMID- 18709013
TI  - Simultaneous EEG and EMG biofeedback for peak performance in musicians.
AB  - The aim of this study was to determine the effects of alpha neurofeedback and EMG
      biofeedback protocols for improvement of musical performance in violinists. The
      sample consisted of 12 music students (10 violinists and 2 viola players) from
      the Faculty of Music, Skopje (3 males, mean age of 20 +/- 0 and 9 females, mean
      age = 20.89 +/- 2.98). Six of them had a low alpha peak frequency (APF) (< 10
      Hz), and six a high APF (> 10 Hz). The sample was randomized in two groups. The
      students from the experimental group participated in 20 sessions of biofeedback
      (alpha/EMG), combined with music practice, while the students from the control
      group did only music practice. Average absolute power, interhemispheric coherence
      in the alpha band, alpha peak frequency (APF), individual alpha band width
      (IABW), amount of alpha suppression (AAS) and surface forehead integrated EMG
      power (IEMG), as well as a score on musical performance and inventories measuring
      anxiety, were assessed. Alpha-EEG/EMG-biofeedback was associated with a
      significant increase in average alpha power, APF and IABW in all the participants
      and with decreases in IEMG only in high-APF musicians. The biofeedback training
      success was positively correlated with the alpha power, IcoH, APF, IABW and
      baseline level of APF and IABW. Alpha-EEG/EMG biofeedback is capable of
      increasing voluntary self-regulation and the quality of musical performance. The
      efficiency of biofeedback training depends on the baseline EEG alpha activity
      status, in particular the APF.

PMID- 18709014
TI  - Expertise in bodily injuries in criminal procedure.
AB  - In the day-to-day practice of answering questions from the area of medicine
      today, there is a growing need for forensic medical expertise in bodily injuries
      in criminal procedure. Furthermore, when qualifying a bodily injury, the expert
      must possess knowledge and experience not only medical, but s/he must also be
      aware of the legal requirements and norms of the Code of Criminal Procedure and
      the Criminal Code of R. Macedonia. This will enable the expert to contribute to
      the explanation and clarification of certain facts and issues relating to the
      bodily injury. In this paper, by citing Articles 255 and 256 of the Code of
      Criminal Procedure, it is explained how an expert can be appropriately selected
      by the court. In addition to this, by citing Article 271 of the afore-mentioned
      Code, a way of analysing bodily injuries is defined; and finally, the definition
      of bodily injuries is explained through citing Articles 130 and 131 of the
      Criminal Code of R. Macedonia, relating to bodily injury and grave bodily injury.
      The aim of this paper is to outline the method of performing this forensic
      medical expertise, i.e. by whom and when can expertise in bodily injuries be
      sought and, moreover, what is the legal and ethical responsibility of the expert
      during the execution of the expertise. Additionally, the steps that the expert
      should follow when preparing a written statement and opinion on the type of the
      bodily injury are explained. More specifically, emphasis is placed on the
      expert's requirements after examination of the injured individual; after revision
      of the medical documentation during expert assessment of bodily injuries in the
      case of criminal subjects; and providing oral statements and opinions during the
      criminal procedure.

PMID- 18709015
TI  - Autologous stem-cell transplantation in patients with multiple myeloma.
AB  - BACKGROUND: - Multiple myeloma is a malignant plasma-cell proliferative disorder,
      the second most common haematologic cancer. Treatment with high-dose therapy
      (HDT) and single autologous stem cell transplantation (ASCT) is a category I
      recommendation of the National Comprehensive Cancer Network. Double
      transplantation can be proposed for patients failing to achieve small a, Cyrillic
      very good partial response (VGPR) after a first ASCT. Aims - The aim of this
      study is to analyse the effect of treatment with high-dose chemotherapy and
      autologous stem-cell support on survival in patients with multiple myeloma, and
      to compare our results with the results from other transplant centres. MATERIAL
      AND METHODS: - during a 7-year period we have performed 20 high-dose chemotherapy
      courses and autologous stem-cell transplantation on 17 patients (3 tandem
      transplantations) with multiple myeloma. In this trial we retrospectively
      analysed the epidemiology characteristics of these patients. Female: 9 Male - 8.
      Median age: 53 years (from 43-64 years). RESULTS: diagnosis was made according to
      Salmon and Durie criteria. High-dose regimen consisted of Melphalan doses of
      200mg/m2. In tandem transplantations the dose of the second high-dose regimen was
      140 mg/m2. The volume of CD34+ cells was approximately 3.8 x 10exp8/Kg.bw. In 3
      patients we used phlebothomy as a source of added stem cells. The period from
      diagnosis to transplantation was 12 months. Of 17 patients 70% are alive, 5 have
      died (3 renal failure, 1 fatal cerebral bleeding and 1 with multiorgan failure).
      The disease-free survival was 22 months in our group of patients. Overall
      survival was 48 months and survival after transplantation was 35 months. The
      probability of 7 years' overall survival exists in 50% of patients. CONCLUSION:
      Patients treated with high-dose chemotherapy followed by autologous stem-cell
      support have a better survival and quality of life compared with patients treated
      with standard chemotherapy.

PMID- 18709016
TI  - Adenosine stress protocols for nuclear cardiology imaging.
AB  - The treadmill test combined with myocardial perfusion imaging (MPI) is a commonly
      used technique in the assessment of coronary artery disease (CAD). However, there
      is a group of patients who may not be able to undergo the treadmill test.
      Pharmacologic stress testing is increasingly utilized for stress perfusion
      imaging and currently accounts for nearly 40% of all nuclear stress testing [8].
      The aim of this study was the introduction of adenosine stress protocols in our
      nuclear laboratory, and the following, recording and comparing of the frequency
      and severity of side-effects. METHODS: We performed two kinds of adenosine stress
      protocols on 186 patients who underwent MPI with radiotracer 99mTc-sestamibi:
      1st: 47 patients underwent AdenoSCAN abbreviated protocol IV. adenosin
      140microg/kg/min for 3 minutes; 2nd: AdenoEX combined with low level 50W bicycle
      exercise in 139 patients. We followed and compared side-effects (minor and major
      events) between AdenoSCAN and AdenoEX protocol, and established an adequate time
      for imaging of both protocols. RESULTS: Compared with AdenoSCAN, AdenoEX protocol
      was tolerated by all patients; it reduced all side-effects and improved image
      quality. Using AdenoEX protocol we found that the heart-to-liver ratio was
      significantly better, and we established a time of imaging of 15 minutes after
      stress, compared to the AdenoSCAN time of imaging which was a minimum of 45
      minutes after stress. CONCLUSION: This study gives advatages to AdenoEX protocol,
      because it had fewer side-effects, improved patients' tolerance, improved image
      quality, and enhanced efficiency and throughput given the opportunity for earlier
      imaging.

PMID- 18709017
TI  - Henoch-Schonlein purpura in an adult patient: extragastric, cutaneous
      manifestation of helicobacter pylori infection.
AB  - Today there is evidence that Helicobacter pylori has a critical role in different
      extragastric diseases. The discovery of a number of other new Helicobacter
      species has stimulated research into different extragastric diseases, in which an
      infectious hypothesis is plausible. Enterohepatic Helicobacter species have been
      hypothesized to play a role in different disorders including the extragastric
      manifestations of H. pylori infection. The authors present a case of Henoch
      Schonlein purpura in an adult patient with Helicobacter pylori infection and
      disease regression after triple anti-Helicobacter eradication therapy. The
      patient was monitored, over a follow-up period of almost 9 years after
      eradication of Helicobacter pylori presence, by clinical examination as well as
      serological findings. There was no disease reccurence during the follow-up period
      and no markers of Helicobacter pylori reinfection. Since disease recurrence
      occurs throughout weeks to months, the authors conclude that Henoch-Schonlein
      purpura is a possible extragastric, cutaneous manifestation of Helicobacter
      pylori infection.

PMID- 18709018
TI  - Sixty years since the foundation of the Medical Faculty at the Ss. Cyril and
      Methodius University in Skopje, R. Macedonia (1947-2007).
AB  - The Medical Faculty (M.F.) in Skopje was founded on 6th March 1947 by a Decree of
      the Government of the Republic of Macedonia. Over the past six decades, the
      Medical Faculty has been and still is a key institution where medical
      professionals, medical doctors and other medical-health personnel have been
      educated, as well as an institution where scientific research and applied health
      activities have been conducted. The first 153 students were enrolled at the
      Faculty in the autumn of 1947. More than 10000 medical doctors and 350 radiology
      technicians have graduated at the Medical Faculty. A total of 315 students have
      finished postgraduate studies and acquired a Master's degree in medical sciences
      and there are 160 active postgraduates at present. The degree of Doctor of
      Medical Sciences has been awarded to 463 candidates, while 93 are in the process
      of preparing their doctoral thesis. Currently the process of introducing three
      year doctoral studies is underway. Since 1992, 2,380 have successsfully passed
      the specialist exam, while 700 specializations are ongoing. The teaching process
      is being conducted by 233 professors and 215 teaching assistants through 33
      departments. The Medical Faculty consists of 12 institutes and 3 teaching bases
      in the pre-clinical segment. The clinical segment consists of 25 clinics, 3
      institutes and 7 teaching bases. The Medical Faculty has published the journal
      Godishen zbornik na Medicinskiot fakultet, which has been renamed Makedonsko
      spisanie za medicina. More than 380 monographs and textbooks have been printed in
      the country or abroad. A total number of 350 scientific projects have been
      undertaken, 40 with international partners. The Medical Faculty in Skopje has
      been a founder and "mother" faculty to the Faculty of Dentistry and the Faculty
      of Pharmacy, also providing, at the same time, interdisciplinary studies at other
      faculties.

PMID- 18709020
TI  - Francois Morel: four decades of interdisciplinary search for the logic of life.

PMID- 18709022
TI  - Adiponectin: good, bad, or just plain ugly?
AB  - It has been suggested that adiponectin has antiatherogenic, anti-inflammatory,
      and insulin-sensitizing properties. However, studies in humans have reported
      inverse as well as positive associations between adiponectin concentrations and
      disease states. This Commentary discusses the apparent conflict in the
      literature.

PMID- 18709023
TI  - Blocking of angiotensin II is more than blocking of transforming growth factor
      beta.
AB  - Fibrosis is a common feature of chronic kidney diseases that is mediated by
      matrix-producing myofibroblasts. One potential origin of myofibroblasts is
      epithelial-mesenchymal transition (EMT) of tubuloepithelial cells. Transforming
      growth factor-beta (TGF-beta) is a key factor inducing EMT. Carvajal et al.
      demonstrate that angiotensin II induces EMT by classical stimulation of TGF-beta
      and also by a TGF-beta-independent pathway, both signaling via Smad molecules.
      Therefore, blockade of angiotensin II is more than lowering of blood pressure and
      inhibition of TGF-beta stimulation.

PMID- 18709024
TI  - Multiple effects of HMG-CoA reductase inhibitors (statins) besides their lipid
      lowering function.
AB  - The paper by Sharyo et al. shows that statins reduce the severity in a model of
      renal-ischemia reperfusion injury and raises the therapeutic possibility of using
      statins as pharmacological intervention against acute kidney injury. This,
      together with previous studies, indicates that statins exert a wide spectrum of
      anti-inflammatory, immunomodulatory, and protective effects besides their lipid
      lowering function.

PMID- 18709025
TI  - Macroautophagy: a mechanism for mediating cell death or for promoting cell
      survival?
AB  - Macroautophagy is a ubiquitous mechanism for the bulk removal of macromolecules
      and cell organelles from the cell. Periyasamy-Thandavan and colleagues report
      that cisplatin activates autophagy in renal tubular cells and that autophagy
      plays a role in decreasing apoptosis of tubular cells induced by cisplatin. This
      finding provides novel evidence that autophagy may play a role in ameliorating
      the effects of acute injury on the kidney.

PMID- 18709026
TI  - Once-yearly intravenous zoledronate does not impair renal function in
      postmenopausal women.
AB  - Zoledronate, a potent third-generation amino-bisphosphonate previously used for
      the treatment of bone metastasis, was recently shown to significantly reduce the
      risk of vertebral and hip fractures in osteoporotic postmenopausal women when
      infused at a dose of 5 mg per year for 3 years. The renal follow-up of this
      pivotal study that included more than 5,000 patients (estimated creatinine
      clearance >30 ml per min) is reported by Boonen et al. and shows the long-term
      renal safety of zoledronate in this osteoporotic population.

PMID- 18709028
TI  - Tinnitus after hemodialysis catheter placement.

PMID- 18709027
TI  - The case / progressive hypertension and proteinuria on anti-angiogenic therapy.

PMID- 18709029
TI  - On the present crisis of confidence between health professionals and the public
      and on some largely-preventable unnatural deaths in the country.

PMID- 18709030
TI  - Correlation of serum cholinesterase level, clinical score at presentation and
      severity of organophosphorous poisoning.
AB  - The aim of the study was to correlate between the clinical score described by
      Peradenya Organophosphorus Poisoning (POP) scale, serum cholinesterase level at
      presentation and severity of poisoning. Consecutive patients of organophosphorous
      poisoning attending Bir Hospital from August 2004 to September 2005 were studied.
      Patients were grouped into mild, moderate and severe poisoning groups according
      to the POP scale. Fifty patients fulfilled the inclusion criteria. The severity
      of poisoning directly correlated with serum cholinesterase level (P<0.001). The
      differences in the mean requirements of atropine on the first day of admission,
      in the total amount of atropine needed to treat and in the average duration of
      hospital stay were significant (P<0.05). There were 26% patients in moderate
      poisoning and only 4% patients in severe poisoning, but a total of 14% of the
      patients died, indicating that patients with even moderate degree of poisoning
      had also died. Both the POP scale severity and derangement in serum
      cholinesterase levels at initial presentation did not correlate with mortality,
      which could be due to various other co-morbidities and inadvertent stoppage of
      atropine infusion particularly at night in the wards. The POP scale and serum
      cholinesterase at presentation appeared useful to assess the severity of
      poisoning, particularly in terms of higher amount of atropine and prolonged
      duration of hospital stay. The patients with evidence of moderate and severe
      degrees of poisoning need close monitoring. Further studies to evaluate the
      factors likely to cause deaths, particularly by closely monitoring of moderate
      and severe organophosphorous poisoning in intensive care units, are required to
      clarify the correlation with mortality.

PMID- 18709031
TI  - Prevalence of Methicillin-resistant Staphylococcus aureus (MRSA) in a Tertiary
      Care Hospital in Eastern Nepal.
AB  - Nosocomial infection is a major problem in the world today. Methicillin-resistant
      Staphylococcus aureus (MRSA) strains, usually resistant to several antibiotics,
      shows a particular ability to spread in hospitals and is now present in most of
      the countries. The aim of the present study was to determine the prevalence of
      MRSA infections and their antimicrobial susceptibility pattern in our hospital
      located in eastern Nepal. Identification of Staphylococcus aureus was confirmed
      by standard methods and the antimicrobial susceptibility testing was performed by
      Kirby-Bauer disc diffusion method. Interpretation criteria were those of the
      national committee for clinical laboratory standards. During a period of one
      year, out of a total of 750 Staphylococcus aureus strains isolated from various
      clinical samples, 196 (26.14%) were found to be Methicillin-resistant. Seventy
      percent isolates of MRSA were from inpatient departments and amongst them only
      10% of the isolates were from intensive care units (ICU). More than 65% of MRSA
      were found to be resistant to Penicillin, Cephalosporins, Ciprofloxacin,
      Gentamicin Erythromycin and Tetracycline, while 47.96% of them were resistant to
      Amikacin. Many MRSA strains were multidrug-resistant. However, no strains were
      resistant to Vancomycin. To reduce the prevalence of MRSA, the regular
      surveillance of hospital acquired infection, isolation nursing of patients who
      carry MRSA, monitoring of antimicrobial susceptibility pattern and formulation of
      a definite antibiotic policy may be helpful.

PMID- 18709032
TI  - The efficacy and safety of low dose epidural butorphanol on postoperative
      analgesia following cesarean delivery.
AB  - Butorphanol is considered an effective and safe analgesic after cesarean delivery
      but is associated with profound dose-dependent sedation. Somnolence may cause
      hindrance in early mother-baby interaction. This study was designed to assess the
      analgesic efficacy and to monitor side-effects of low doses (0.5 mg and 0.75 mg)
      of epidural butorphanol with bupivacaine compared to bupivacaine alone in
      parturients following cesarean delivery. One hundred and twenty parturients
      (American Society of Anesthesiologists physical status 1 and 2) undergoing
      cesarean delivery were allocated into three groups: group 1 received epidural
      0.125% bupivacaine while group 2 and 3 received an additional 0.5 mg and 0.75 mg
      butorphanol respectively. A combined spinal, epidural technique was used. Spinal
      anaesthesia was used for surgery. The epidural route was used for postoperative
      analgesia with the study drug. Onset, duration and quality of analgesia, lowest
      visual analogue scales (VAS) score, and side effects were noted. The onset and
      duration of analgesia in group 2 (4.1+/-2.6 min and 202.4+/-62.8 min) and group 3
      (4.0+/-2.5 min and 192.3+/-69.1 min) were significantly different (P<0.01) from
      group 1 (6.6+/-2.7 min and 145.7+/-89.6 min). The quality of analgesia in terms
      of time to first independent movement and satisfactory VAS were statistically
      better (P<0.01) in group 2 (3.9+/-0.3 hour and 8.1+/-0.1 mm) and group 3 (3.8+/
      0.4 hour and 8.1+/-0.9 mm) than in group 1 (5.2+/-0.4 hour and 6.3+/-1.3 mm). The
      incidence of sedation was 5% in all the three groups. A lower dose of epidural
      butorphanol with bupivacaine produces a significantly earlier onset, longer
      duration and better quality of analgesia than bupivacaine does.

PMID- 18709033
TI  - Mammographic diagnosis of breast carcinoma: an institutional experience.
AB  - Mammogram is a common diagnostic modality for breast carcinoma. Diagnostic
      mammogram is available at only few centers in Nepal. The aim of this study was to
      determine the accuracy of diagnostic mammogram in Nepalese women suffering from
      breast carcinoma. A retrospective analysis of the breast carcinoma was carried
      out in the Department of Surgery, Tribhuwan University Teaching Hospital from
      October 1995 to October 2007. Out of 556 patients with histologically proven
      breast carcinoma, 378 patients (68%) had undergone mammography. Breast carcinoma
      was identified on mammography in 328 (87%) cases while 50 cases (13%) were
      reported as normal or benign lesions. Diagnostic mammogram had a sensitivity of
      86.8%, a specificity of 98.6% with a positive predictive value of 68.8% and a
      negative predictive value of 99.5%. In mammographically missed breast carcinoma,
      34% were less than 40 years of age (P<0.05), 60% were premenopausal (P<0.05) and
      88% patients presented with a painless lump. The study shows that the diagnostic
      accuracy of the mammogram is very high. However, there is a chance of missing the
      breast carcinoma in young and premenopausal women.

PMID- 18709034
TI  - Outcome of supracondylar fractures of the humerus in children treated by closed
      reduction and percutaneous pinning.
AB  - Supracondylar fractures of humerus in children are common injuries. Displaced
      fractures are inherently unstable. Conservative treatment results in malunion.
      Open reduction and internal fixation (ORIF) is more invasive and recovery is
      prolonged. From September 2004 to September 2005, 102 displaced supracondylar
      fractures of humerus, aged between one and half year to 13 years, were treated
      using close reduction and percutaneous Kirschner (K) wire fixation under c-arm
      fluoroscopy. Seventy nine patients were treated by cross K-wires and in twenty
      three cases lateral two K-wires were put. Above elbow plaster of paris back slab
      was applied in all cases for at least four weeks. Back slab, K-wires were removed
      after four weeks and elbow range of motion exercise was started. Results were
      analyzed using Flynn's criteria. All patients were followed up to 14th week
      postoperatively. In cross K-wire group(N=79) 70.8% had excellent, 22.7% good,
      3.8% fair and 2.5% had poor results at eight weeks follow up which was improved
      to 91.1% excellent, 6.3 good, 1.2% fair and 1.26% poor results at 14 weeks follow
      up. In lateral K-wire group (N=23) 70% had excellent, 21.7% good, 4.3% fair and
      4.3% had poor result at eighth week which was improved to 91.3% excellent, 4.3%
      good, 4.3% fair and no poor result at 14th week follow up. Eight patients got
      superficial pin tract infection and seven patients sustained ulnar nerve injury
      post operatively. We recommend this procedure for displaced supracondylar
      fractures in children as it is safe and cost effective procedure with acceptable
      complication rates.

PMID- 18709035
TI  - Early detection of precursors of cervical cancer with cervical cytology and
      visual inspection of cervix with acetic Acid.
AB  - A hospital-based, prospective study was done in 350 women of 20-50 years to
      compare VIA with Pap smear for early detection of cervical dysplasia at Maternity
      Hospital, Thapathali, from May 2004 to December 2004. Pap smear was taken from
      each woman followed by VIA. Women with positive VIA and/or positive Pap smear
      were referred for colposcopy-directed cervical biopsy. The variables studied were
      age group, presenting complaint, age of marriage, parity, smoking habit and
      appearance of cervix. The incidence of positive VIA and Pap smear was 2.86 and
      0.57 respectively. Pelvic pain was the most common presenting complaint. The
      majority of the women were married before 20 years of age. All women with either
      positive VIA and/or Pap smear were of parity two or above. There was no
      significant association between smoking and positive VIA (P=0.699) or Pap smear
      (P=0.397). Approximately 36.57% of the women screened had abnormal looking
      cervix. There were two women with high grade intraepithelial lesion (HSIL) and
      both were VIA positive and this was statistically significant (Fischer exact
      P=0.0007). Of the ten VIA positive women, on histopathological examination six
      showed chronic cervicitis, one acute cervicitis, one showed cervical
      intraepithelial neoplasia (CIN) II, one had normal finding and one was lost to
      follow up. VIA as a screening test for cervical neoplasia did not miss any lesion
      detected by Pap smear and confirmed by cervical biopsy.

PMID- 18709036
TI  - Work related complaints among dentists.
AB  - The objective of this study was to describe the occurrence of neck pain, shoulder
      pain and back pain among dentists and to assess the risk factors affecting them.
      Sixty-eight dentists from Dharan and Biratnagar were interviewed using pretested
      questionnaires in January 2006. Back pain was the most common complaint affecting
      almost 80% of the study population, followed by neck pain (58.8%) and shoulder
      pain (47%). The frequency of shoulder pain among female dentists was nearly
      double that of males (P=0.009). The mean days of neck pain among males was
      significantly higher as compared to females (P=0.048). The study suggests that
      musculoskeletal complaints are common among dentists, though they are not of
      severe nature. There is a scope for further decreasing the prevalence and
      severity of these disorders by performing regular specific exercises.

PMID- 18709037
TI  - Two-hit hypothesis and multiple organ dysfunction syndrome.
AB  - A severe insult in the form of infection or trauma primes the host immune system
      so that a subsequent, relatively trivial insult produces a markedly exaggerated
      host immune response, which can lead to multiple organ dysfunction syndrome
      (MODS) and death. This forms the basis of the "two-hit hypothesis" (THH), which
      is being increasingly recognised as an important cause of morbidity and mortality
      following severe injury and sepsis, particularly in intensive care settings.
      Appreciation of the impact of repeated insults and pathophysiology of MODS is
      vital in the prevention of this serious complication. We describe a case which
      illustrates the concept of THH and MODS and present a review of literature on
      this subject.

PMID- 18709038
TI  - Erosive oral lichen planus and its management: a case series.
AB  - Lichen planus (LP), although a dermatosis, is more common in the oral mucous
      membrane than in the skin. Lesions of oral LP are classically found on the buccal
      mucosa and gingiva. Among the various types, the reticular lesions are
      asymptomatic and require no treatment, but pain and severe discomfort accompany
      the erosive or ulcerative lesions. Malignant transformation to squamous cell
      carcinoma developing in areas of erosive oral LP (EOLP) being a possibility, it
      is important for clinicians to maintain a high index of suspicion for all
      intraoral lichenoid lesions. Therefore, periodic follow-up of all patients with
      EOLP is recommended. In view of the above, this paper highlights the management
      of four cases of EOLP with topical corticosteroid and CO2 laser surgery.

PMID- 18709039
TI  - A cluster survey for determination of regular vaccination coverage among
      children.
AB  - One of the objectives of the Expanded Program of Immunization (EPI) is to achieve
      and sustain vaccination coverage to >90%. The coverage is not uniform within the
      districts, some of the areas showing more than 100% while others are far behind.
      The objective of the survey was to determine the coverage of immunization among
      children 12-23 months of age in Rautahat District of Nepal. A cross-sectional
      method was applied with the 30-cluster sampling method followed by taking a
      sample of 210 children. The structured questionnaire requesting information about
      socio-economic characteristics, vaccination, history of vaccination, doses of
      vaccines, and vaccination records were used for collecting data. The coverage
      responses according to history from mothers for BCG, DPTHb-3, Polio3 and Measles
      immunizations were 96.7%, 90.0%, 97.6% and 78.1% respectively. By analyzing the
      records of the sampled Village Development Committees (VDCs), the coverage for
      the same vaccines was 88.1%, 78.1%, 79.0, 73.8% respectively. The drop-out of BCG
      versus measles was also very high. The District Health Office (DHO) reports were
      remarkably higher than the coverage of immunizations obtained by the survey,
      showing additional number of the target children.

PMID- 18709040
TI  - Melanoma in New Zealand: a problem that is not going away.

PMID- 18709041
TI  - Ghosts in the machine: the experiences of Maori in the New Zealand health system.

PMID- 18709042
TI  - Lack of progress in New Zealand's Cancer Control Strategy.

PMID- 18709043
TI  - Defamatory articles or not?

PMID- 18709044
TI  - The incidence and thickness of cutaneous malignant melanoma in New Zealand 1994
      2004.
AB  - AIM: To examine the incidence of thick melanoma in New Zealand from 1994-2004 and
      investigate associations with melanoma thickness. METHOD: The New Zealand Health
      Information Service provided information on all registrations for malignant
      melanoma from 1994-2004. Age-standardised registration rates were calculated.
      Logistic regression analysis was undertaken to identify factors associated with
      melanoma thickness. RESULTS: The incidence of thick melanoma did not decrease
      during 1994-2004. There were statistically significant associations for age,
      gender, ethnic group, and type of melanoma with melanoma thickness. Of those
      diagnosed with melanoma, the proportion with thick melanoma was greater for older
      than younger people, for males compared with females, for Maori compared with non
      Maori (despite the lower incidence in Maori), and for those diagnosed with
      nodular melanoma compared with other types of melanoma. CONCLUSION: Strategies to
      encourage the early detection of melanoma in New Zealand have not yet reduced the
      incidence of thick melanomas. This may be because it is too soon to see the
      impact of early detection, or because early detection strategies predominantly
      identify melanomas that are unlikely to progress, but miss thicker nodular
      melanomas.

PMID- 18709045
TI  - The road we travel: Maori experience of cancer.
AB  - AIM: This research explores Maori experiences of cancer. It does so to shed light
      on the causes of cancer inequalities for Maori. METHODS: The views of 44 Maori
      affected by cancer--including patients, survivors, and their whanau (extended
      families)--were gathered in five hui (focus groups) and eight interviews in the
      Horowhenua, Manawatu, and Tairawhiti districts of New Zealand. After initial
      analysis, a feedback hui was held to validate the findings. RESULTS: Maori
      identified effective providers of cancer services such as Maori health providers.
      They also identified positive and negative experiences with health professionals.
      The involvement of whanau in the cancer journey was viewed as highly significant
      as was a holistic approach to care. Participants had many suggestions for
      improvements to cancer services such as better resourcing of Maori providers,
      cultural competence training for all health workers, the use of systems
      'navigators', and the inclusion of whanau in the cancer control continuum.
      CONCLUSION: The research identifies a range of health system, healthcare process,
      and patient level factors that contribute to inequalities in cancer for Maori. It
      also explores the role of racism as a root cause of these inequalities and calls
      for urgent action.

PMID- 18709046
TI  - Thyroid malignancies: a New Zealand South Island thyroid clinic experience 1995
      2006.
AB  - AIM: To assess the number and histological type of thyroid malignancies occurring
      in the northern half of New Zealand's South Island (referral population of
      553,000). METHODS: Patients with newly diagnosed thyroid malignancies seen at
      thyroid clinic, Christchurch Hospital between 1995 and 2006 were identified from
      the thyroid clinic database, and the histological diagnoses and clinical features
      were reviewed from hospital records. RESULTS: During the 12-year study period,
      213 patients with thyroid malignancy were identified. The majority had thyroid
      cancer of follicular cell origin--184 differentiated thyroid cancers (DTC) and 9
      anaplastic thyroid cancers. The DTC patients included 130 with papillary thyroid
      cancers (PTC)--71%; 33 follicular thyroid cancers (FTC)-18%; and 21 Hurthle cell
      thyroid cancers (HTC)-11%. One of the papillary cancer patients had a mixed
      papillary-medullary tumour. The 184 DTC patients included five patients with an
      immediate family member with thyroid cancer--including a mother-son pair with
      papillary cancer. Tumours of nonfollicular cell origin included 12 medullary
      thyroid cancers (6% of primary thyroid malignancies), and all were apparently
      sporadic, 7 primary thyroid lymphomas, and 2 thyroid metastases. The female-male
      ratio was >/=2 in all patient groups with primary thyroid malignancies. The
      median age for both PTC and FTC groups was 48 y, with Hurthle cell, anaplastic,
      and lymphomas occurring in older patients. The 3 paediatric patients (<16 y) all
      had PTC. CONCLUSIONS: In the 12-year study period the majority (90%) of thyroid
      malignancies were of follicular cell origin--184 DTC (papillary 130, follicular
      33, and Hurthle 21), and 9 anaplastic cancers. Tumours of non-follicular cell
      origin were uncommon and included medullary cancers, lymphomas, and metastases.
      Short-term follow up (median 6 y) confirms that anaplastic thyroid cancer is
      highly malignant, and the only patients with differentiated thyroid cancer with
      early cancer deaths had presented with advanced disease and were > 55 years at
      diagnosis.

PMID- 18709047
TI  - An audit of colon cancer data on the New Zealand Cancer Registry.
AB  - AIMS: This study aims to assess the reliability of New Zealand Cancer Registry
      data on colon cancer. METHODS: Data from a review of the clinical records of 642
      people diagnosed with colon cancer between 1996 and 2003 were used to audit the
      data held on these individuals by the New Zealand Cancer Registry (NZCR). The
      record review data were treated as the "gold standard". RESULTS: Age at diagnosis
      (measured in years) recorded by NZCR was 96% accurate, and date of diagnosis was
      within 6 weeks of the clinical date of diagnosis in more than 97% of cases.
      Overall tumour site was recorded with more than 95% accuracy, with 86% accuracy
      for tumour sub-site within the colon. Tumour grade was only recorded consistently
      by the NZCR from 1999 onwards, from which time the NZCR was 83% accurate for
      tumour grade. Tumour stage was the least accurate variable studied, with 80%
      accuracy. The NZCR data quality improved over the period of this study.
      CONCLUSIONS: The accuracy of the NZCR appears to be similar to that found in
      comparable audits of cancer registries, with stage being the hardest variable for
      registries to collect accurate information on. NZCR data could be improved by
      improving the quality of information provided to the registry.

PMID- 18709048
TI  - The value of voluntary morbidity and mortality meetings at a New Zealand
      metropolitan hospital.
AB  - AIM: To assess the value and outcomes of contemporary, voluntary meetings
      reviewing the morbidity and mortality among surgical patients presenting at a New
      Zealand metropolitan hospital. METHODS: Data on morbidity and mortality were
      prospectively collected and analysed over a two year period (March 2005-August
      2007) from weekly departmental meetings. Patients were discussed on a patient by
      patient basis; the details and outcomes of this were formally constituted and
      documented into a database. Actual mortality numbers and unplanned returns to
      theatre were obtained from clinical coding. Consultant attendance was documented
      RESULTS: Morbidity and mortality was recorded and discussed in 900 patients (6.5%
      of total admissions). Morbidity was discussed in 738 patients (incidence 5%); 190
      (1.4%) deaths were discussed. Only 58% of unplanned returns to theatre and 62% of
      mortality recorded by clinical coding were discussed. However 54% of unplanned
      returns to theatre and 35% of mortality that were discussed were not recorded by
      clinical coding. It was felt that the clinical pathway had been appropriate in
      88% and 91% of discussed morbidity and mortality, respectively. Over time, there
      was no significant change in consultant attendance (7/13 at 6 months vs 7/13 at 2
      years, p=NS) and no trend in the median number of patients discussed per month.
      CONCLUSIONS: In the setting of a voluntary morbidity and mortality meeting only
      12% and 8% of patients discussed, respectively, resulted in further action being
      initiated. Despite there being significant under-reporting of both morbidity and
      mortality, this format identified data that had previously been missed by
      hospital coding. If value is gained from the morbidity and mortality meetings, it
      is not reflected in consultant attendance or in the number of patients submitted
      for discussion as these did not change over time.

PMID- 18709049
TI  - Hospital discharges in New Zealand 1991-2005: changes over time and variation
      between districts.
AB  - AIM: This paper describes changes in the rate of hospital discharges in New
      Zealand between 1991 and 2006, and assesses variation across districts; it
      contributes to the discussion of the adequacy of the health system. METHODOLOGY:
      Data on public hospital discharges were obtained from the NZ Health Information
      Service. Diagnostic Related Groups were used to group and weight cases;
      domiciliary codes were used to assign cases to districts and as an indication of
      patients' socioeconomic status. The Intervention Ratio was used as a relative
      measure of national hospital throughput from 1991 to 2005, and of district
      service volume. The Coefficient of Variation was used as a measure of overall
      system variation. RESULTS: There has been an increase of 50.5% in weighted
      discharges from public hospitals between 1991/2 and 2005/6; adjusted for
      population change the increase is 17.9%. There has been a modest fall in the
      degree of variation between districts, but in medicine and surgery 24% of
      district departments appear to have levels of discharge significantly above or
      below the national average. CONCLUSIONS: The intensity of public hospital care to
      the New Zealand public has increased. Where services are provided at a level
      above or below the national average, local explanations should be sought and
      corrective action undertaken if warranted.

PMID- 18709050
TI  - Mapping progress: the evaluation and monitoring work of the Cancer Control
      Council of New Zealand 2005-2007.
AB  - The Cancer Control Council of New Zealand was established in 2005 to provide an
      independent, sustainable focus for cancer control. One of its key roles is to
      monitor and review implementation of the Cancer Control Strategy.

PMID- 18709051
TI  - From screening criteria to colorectal cancer screening: what can New Zealand
      learn from other countries?
AB  - New Zealand is currently exploring how population-based colorectal cancer (CRC)
      screening will be implemented. The United Kingdom (UK), Australia, France, Italy,
      Spain, Finland, Denmark, the Netherlands, and Switzerland have conducted or are
      currently conducting pilot/feasibility studies. The UK, Australia, Finland,
      Canada, France and Italy are all in the early stages of implementing population
      based CRC screening programmes. Most of these countries have lower CRC mortality
      rates than New Zealand. New Zealand is in a good position to learn from this
      overseas experience. Some of the key areas that will require careful
      consideration include; the best use of a population register to identify and
      invite eligible participants; the type of screening test to be used; ensuring
      adequate colonoscopy capacity; efficient and effective information systems; the
      management of high-risk groups; and how to ensure that all population groups
      benefit from screening.

PMID- 18709052
TI  - Primary gastric mucosal melanoma.

PMID- 18709053
TI  - The escape artist! Detecting choroidal metastases in the setting of breast
      cancer.

PMID- 18709054
TI  - Medical image. Mediastinal mass in a patient with coronary artery disease.

PMID- 18709055
TI  - Medical image. CT colonography for colovesical fistula.

PMID- 18709056
TI  - Use of title 'Dr'--view of the Medical Council of New Zealand.

PMID- 18709058
TI  - The International Study of Asthma and Allergies in Childhood (ISAAC).

PMID- 18709057
TI  - Abuse of the title 'Dr'.

PMID- 18709059
TI  - Undergraduate education to address patient safety.

PMID- 18709060
TI  - Multifilter rotating shadowband radiometer calibration for spectral aerosol
      optical depth retrievals over Sao Paulo City, Brazil.
AB  - Multifilter rotating shadowband radiometer (MFRSR) calibration values for aerosol
      optical depth (AOD) retrievals were determined by means of the general method
      formulated by Forgan [Appl. Opt.33, 4841 (1994)] at a polluted urban site. The
      obtained precision is comparable with the classical method, the Langley plot,
      applied on clean mountaintops distant of pollution sources. The AOD retrieved
      over Sao Paulo City with both calibration procedures is compared with the Aerosol
      Robotic Network data. The observed results are similar, and, except for the
      shortest wavelength (415 nm), the MFRSR's AOD is systematically overestimated by
      approximately 0.03.

PMID- 18709061
TI  - Improvement of amplified spontaneous emission by encapsulating green fluorescent
      dye in inverted-opal titania photonic crystals.
AB  - Amplified spontaneous emission (ASE) characteristics of a green fluorescent dye
      (10-(2-benzothiazolyl)-1,1,7,7-tetramethyl-2,3,6,7-tetrahydro-1H,5H,11H-[1] benzo
      pyrano [6,7,8-ij]quinolizin-11-one) (C545T) encapsulated in a highly ordered
      three-dimensional (3D) inverted-opal titania (TiO(2)) photonic crystal (PC)
      microcavity were studied. Due to the utilization of a TiO(2) PC, the emission
      spectrum was greatly narrowed and the ASE threshold, gain, and loss were
      significantly improved. The threshold, gain, and loss reached 1.25 mJ pulse(-1)
      cm(-2), 34.69 cm(-1), and 16.9 cm(-1), respectively. The possible reason for the
      improvement in the ASE performance by the PC is attributed to the 3D photon
      localization by the microcavity effect of the PC.

PMID- 18709062
TI  - Mode-locked Yb-doped fiber laser with external compression to 89 fs in normal
      dispersion fiber.
AB  - A practical ytterbium-doped mode-locked fiber source producing 89 fs pulses
      without an external bulk compensator was developed by investigating the pulse
      propagation dynamics in a mode-locked fiber laser with small average dispersion.
      Negatively chirped pulses are taken from the cavity and compressed in a standard
      output fiber resulting in high-quality pulses.

PMID- 18709063
TI  - Analytical expression for femtosecond-pulsed Z scans on instantaneous
      nonlinearity.
AB  - By employing the Gaussian decomposition method, the analytical formulas of the
      Gaussian-beam Z-scan traces have been derived for an optically thin material
      exhibiting both refractive and absorptive parts of third-order nonlinearity, with
      Gaussian or hyperbolic secant squared laser pulses of femtosecond duration. The
      formulas have been verified experimentally with femtosecond-pulsed Z scans on a
      carbon disulfide and acetone solution of a chalcone derivative
      (0.95C(18)H(17)ClO(4) . 0.05C(17)H(14)Cl(2)O(3)). An efficient yet accurate
      analytical technique has been demonstrated for extracting both the nonlinear
      refraction coefficient and the nonlinear absorption coefficient from a single
      closed-aperture Z-scan trace.

PMID- 18709065
TI  - Self-referenced interferometry for the characterization of axicon lens quality.
AB  - A simple interferometer for the characterization of axicon lenses is presented.
      The phase cone acquired by a wave propagating through an axicon, when interfered
      with a collinear reference wave, produces a nearly cylindrically symmetric self
      referenced interference pattern from which the distortions of the axicon surface
      may be readily obtained. Comparison with two-dimensional off-axis interferometry
      is used to validate the self-referenced technique. The measurements are based on
      retrieval of the accrued spatial phase distribution from interference fringes
      with on- and off-axis reference beams and are found to be equivalent. We use the
      ellipticity of the phase maps to qualify axicon lenses, which are expected to
      exhibit radial symmetry and engage the self-referential capability of the on-axis
      method to derive deviation maps that characterize the surface quality of the
      axicons.

PMID- 18709064
TI  - Digital micromirror device as a spatial illuminator for fluorescence lifetime and
      hyperspectral imaging.
AB  - Time-domain fluorescence lifetime imaging (FLIM) and hyper-spectral imaging (HSI)
      are two advanced microscopy techniques widely used in biological studies.
      Typically both FLIM and HSI are performed with either a whole-field or raster
      scanning approach, which often prove to be technically complex and expensive,
      requiring the user to accept a compromise among precision, speed, and spatial
      resolution. We propose the use of a digital micromirror device (DMD) as a spatial
      illuminator for time-domain FLIM and HSI with a laser diode excitation source.
      The rather unique features of the DMD allow both random and parallel access to
      regions of interest (ROIs) on the sample, in a very rapid and repeatable fashion.
      As a consequence both spectral and lifetime images can be acquired with a
      precision normally associated with single-point systems but with a high degree of
      flexibility in their spatial construction. In addition, the DMD system offers a
      very efficient way of implementing a global analysis approach for FLIM, where
      average fluorescence decay parameters are first acquired for a ROI and then used
      as initial estimates in determining their spatial distribution within the ROI.
      Experimental results obtained on phantoms employing fluorescent dyes clearly show
      how the DMD method supports both spectral and temporal separation for target
      identification in HSI and FLIM, respectively.

PMID- 18709066
TI  - Development of a spectrometer using a continuous wave distributed feedback
      quantum cascade laser operating at room temperature for the simultaneous analysis
      of N2O and CH4 in the Earth's atmosphere.
AB  - We report on the development and performance of a gas sensor based on a
      distributed feedback quantum cascade laser operating in continuous wave at room
      temperature for simultaneous measurement of nitrous oxide (N(2)O) and methane
      (CH(4)) concentrations at ground level. The concentrations of the gases are
      determined by a long path infrared diode laser absorption spectroscopy. The long
      term stability of the instrument is evaluated using the Allan variance technique.
      A preliminary evaluation of the instrument performance is realized by in situ
      measurements of N(2)O and CH(4) concentrations at ground level during 1 day. The
      sensor has also been applied to study the time response of N(2)O concentrations
      to a fertilizer addition in a soil sample and for the comparison between various
      types of soils.

PMID- 18709067
TI  - High-resolution refractive index anisotropy measurement in optical fibers through
      phase retardation modulation.
AB  - We present an improved, high-resolution method for the measurement of phase
      retardation induced by the material birefringence of optical fibers. Such a
      method can be used to retrieve information about the spatial distribution of
      refractive index anisotropy in the fiber by comparing the accumulated phase of a
      polarization component oriented along the fiber transmission axis and another
      located in the transverse plane. The method is based on the nonlinear regression
      of a phase modulated signal of known modulation amplitude altered by the sample.
      Experimental results obtained with our method for a standard telecommunications
      fiber (the Corning SMF-28) as well as photosensitive fibers (Fibercore PS1250 and
      PS1500) are presented with a noise-limited phase resolution below 10(-4) radians
      and a spatial resolution below 1 microm. An analysis of the limitation of such
      measurement methods is also presented including diffraction by the fibers.

PMID- 18709069
TI  - Effect of post-epitaxial-growth processing on the nonlinear response of saturable
      absorber.
AB  - The nonlinear response of an ion-irradiated saturable Bragg reflector, further
      modified by thermal annealing, has been studied. We demonstrate that the
      absorption recovery time and the effective saturation fluence dependent on the
      pulse duration can be tailored over a wide range after epitaxial growth by the
      proper combination of ion irradiation and subsequent annealing. Thermal treatment
      is also an efficient means for the reduction of the unbleachable losses and the
      stabilization of the absorber parameters.

PMID- 18709068
TI  - Hyperspectral Fourier transform spectrometer for reflection spectroscopy and
      spectral self-interference fluorescence microscopy.
AB  - A hyperspectral Fourier transform spectrometer has been developed for studying
      biological material bound to optically reflecting surfaces. This instrument has
      two modes of operation: a white-light reflection mode and a spectral self
      interference fluorescence mode. With the combined capability, information about
      the conformation of an ensemble of biomolecules may be determined. To the best of
      our knowledge, ours is the first report of this hybrid white-light reflection,
      spectral self-interference fluorescence measurement with any type of
      hyperspectral imager. The measurement technique is presented along with a full
      description of the system, including theoretical performance projections. Proof
      of-principle measurements of artificial samples are shown, and the results are
      discussed.

PMID- 18709070
TI  - Single actuator alignment control for improved frequency stability of a cavity
      based optical frequency reference.
AB  - We demonstrate a method of controlling the alignment of a laser beam to a Fabry
      Perot resonator through synchronous detection of the misalignment arising from
      modulating the orientation of a single beam-steering mirror. The horizontal and
      vertical tilt of the mirror are modulated in quadrature to drive a circular
      motion of the beam orientation. A corresponding modulation of the intensity of
      the optical field circulating in the cavity is measured at either the reflected
      or transmitted port and demodulated synchronously to derive two error signals to
      indicate the vertical and horizontal misalignment. These signals are fed back to
      the beam-steering mirror to suppress fluctuations below 30 Hz. This method avoids
      the complexity of monitoring off-axis cavity modes and is particularly effective
      in the case where unwanted pointing fluctuations are introduced by one or two
      elements in the optical setup. We have applied the technique to two Fabry-Perot
      resonators in use as precision frequency references, delivering a result of 10 dB
      suppression of alignment fluctuations at 1 Hz and an improvement in frequency
      stability by up to a factor of 4.

PMID- 18709071
TI  - Photodarkening rate in Yb-doped silica fibers.
AB  - Yb-doped fibers are widely used in laser applications requiring high average
      output powers and high-peak-power pulse amplification. Photodarkening (PD) is
      recognized as one limiting factor in these fibers when pumped with high-intensity
      radiation. We describe an approach for performing quantitative PD studies of
      fibers, and we present measurements of the rate of PD in Yb-doped single-mode
      fibers with varying inversion levels. The method is applicable to large-mode-area
      fibers. We observed a seventh-order dependence of the PD rate on the excited
      state Yb concentration for two different fibers; this result implies that PD of a
      Yb-doped fiber source fabricated using a particular fiber will be strongly
      dependent on the configuration of the device.

PMID- 18709072
TI  - Dynamics of interacting Brownian particles in concentrated colloidal suspensions.
AB  - We are concerned with dynamic properties of interacting Brownian particles in
      concentrated colloidal suspensions. An effective diffusion coefficient measured
      by the modulated in phase low-coherence dynamic light scattering technique is
      investigated as a function of the volume fraction. The experimental results are
      compared with the numerical ones calculated under both the Cohen-de Schepper
      approximation for hydrodynamic interaction and the Percus-Yevick approximations
      for structural effect. It is confirmed that the Brownian motion of particles in
      the range of volume fraction from 0.01 to 0.2 is mainly dominated by the
      hydrodynamic interaction rather than the structural effect, which can be
      described well by the Cohen-de Schepper approximation.

PMID- 18709073
TI  - Spectral amplitude coding OCDMA using and subtraction technique.
AB  - An optical decoding technique is proposed for a spectral-amplitude-coding-optical
      code division multiple access, namely, the AND subtraction technique. The theory
      is being elaborated and experimental results have been done by comparing a double
      weight code against the existing code, Hadamard. We have proved that the and
      subtraction technique gives better bit error rate performance than the
      conventional complementary subtraction technique against the received power
      level.

PMID- 18709074
TI  - Mid-infrared gas sensing using a photonic bandgap fiber.
AB  - We demonstrate methane sensing based on Fourier transform infrared spectroscopy
      using a hollow-core photonic bandgap fiber guiding in the mid-infrared and idler
      pulses from a femtosecond optical parametric oscillator. Transmission
      measurements are presented for several fibers, and sensing is demonstrated using
      a fiber whose bandgap overlaps the methane fundamental absorption lines. The gas
      filling process of the air core is described, and qualitative methane
      concentrations measurements to 1000 ppm (parts in 10(6)) are reported. Operation
      down to 50 ppm based on our current experiment is predicted.

PMID- 18709075
TI  - Coloring linens with excimer lasers to simulate the body image of the Turin
      Shroud.
AB  - The body image of the Turin Shroud has not yet been explained by traditional
      science; so a great interest in a possible mechanism of image formation still
      exists. We present preliminary results of excimer laser irradiation (wavelength
      of 308 nm) of a raw linen fabric and of a linen cloth. The permanent coloration
      of both linens is a threshold effect of the laser beam intensity, and it can be
      achieved only in a narrow range of irradiation parameters, which are strongly
      dependent on the pulse width and time sequence of laser shots. We also obtained
      the first direct evidence of latent images impressed on linen that appear in a
      relatively long period (one year) after laser irradiation that at first did not
      generate a clear image. The results are compared with the characteristics of the
      Turin Shroud, reflecting the possibility that a burst of directional ultraviolet
      radiation may have played a role in the formation of the Shroud image.

PMID- 18709076
TI  - Terahertz imaging system performance model for concealed-weapon identification.
AB  - The U.S. Army Night Vision and Electronic Sensors Directorate (NVESD) and the
      U.S. Army Research Laboratory have developed a terahertz (THz) -band imaging
      system performance model for detection and identification of concealed weaponry.
      The MATLAB-based model accounts for the effects of all critical sensor and
      display components and for the effects of atmospheric attenuation, concealment
      material attenuation, and active illumination. The model is based on recent U.S.
      Army NVESD sensor performance modeling technology that couples system design
      parameters to observer-sensor field performance by using the acquire methodology
      for weapon identification performance predictions. This THz model has been
      developed in support of the Defense Advanced Research Project Agencies' Terahertz
      Imaging Focal-Plane Technology (TIFT) program and is currently being used to
      guide the design and development of a 0.650 THz active-passive imaging system.
      This paper will describe the THz model in detail, provide and discuss initial
      modeling results for a prototype THz imaging system, and outline plans to
      calibrate and validate the model through human perception testing.

PMID- 18709077
TI  - Adaptive optics technique to overcome the turbulence in a large-aperture
      collimator.
AB  - A collimator with a long focal length and large aperture is a very important
      apparatus for testing large-aperture optical systems. But it suffers from
      internal air turbulence, which may limit its performance and reduce the testing
      accuracy. To overcome this problem, an adaptive optics system is introduced to
      compensate for the turbulence. This system includes a liquid crystal on silicon
      device as a wavefront corrector and a Shack-Hartmann wavefront sensor. After
      correction, we can get a plane wavefront with rms of about 0.017 lambda
      (lambda=0.6328 microm) emitted out of a larger than 500 mm diameter aperture. The
      whole system reaches diffraction-limited resolution.

PMID- 18709078
TI  - Simulation, implementation, and analysis of an optical fiber bundle distance
      sensor with single mode illumination.
AB  - A simulation model for an optical fiber bundle distance sensor with a single mode
      fiber as the illumination fiber and a multimode fiber as the receiving fiber is
      presented. Approximating the illumination light exiting the single mode fiber as
      having a Gaussian intensity profile, a closed-form solution of the reflected
      light coupled into the receiving fiber was derived. A distance sensor was
      implemented and the measured sensor outputs were compared with the simulation
      data to verify the theoretical model. The performance of the distance sensor with
      different design parameters was analyzed. Design guidelines for achieving desired
      sensor performances are suggested.

PMID- 18709079
TI  - Hilbert transform analysis of a time series of speckle interferograms with a
      temporal carrier.
AB  - We present an optical phase measurement method based on the Hilbert transform for
      the analysis of a time series of speckle interferograms modulated by a temporal
      carrier. We discuss the influence of nonmodulating pixels, modulation loss, and
      noise that affect the bias and modulation intensities of the interferometric
      signal and propose the application of the empirical mode decomposition method for
      its minimization. We also show the equivalence between the phase recovery
      approaches that are based on the Hilbert and the Fourier transforms. Finally, we
      present a numerical comparison between these methods using computer-simulated
      speckle interferograms modulated with a temporal carrier.

PMID- 18709080
TI  - Laboratory demonstration of accurate and efficient nanometer-level wavefront
      control for extreme adaptive optics.
AB  - A 32 x 32 microelectricalmechanical systems mirror is controlled in a closed-loop
      adaptive optics test bed with a spatially filtered wavefront sensor (WFS),
      Fourier transform wavefront reconstruction, and calibration of references with a
      high-precision interferometer. When correcting the inherent aberration of the
      mirror, 0.7 nm rms phase error in the controllable band is achieved. When
      correcting an etched phase plate with atmospheric statistics, a dark hole 10(3)
      deeper than the uncontrollable phase is produced in the phase power spectral
      density. Compensation of the mirror's influence function is done with a Fourier
      filter, which results in improved loop convergence. Use of the spatial filter is
      shown to reduce the gain variability of the WFS in a quadcell configuration.

PMID- 18709081
TI  - Tilt sensitivity of the two-grating interferometer.
AB  - Fringe formation in the two-grating interferometer is analyzed in the presence of
      a small parallelism error between the diffraction gratings assumed in the
      direction of grating shear. Our analysis shows that with partially coherent
      illumination, fringe contrast in the interference plane is reduced in the
      presence of nonzero grating tilt with the effect proportional to the grating tilt
      angle and the grating spatial frequencies. Our analysis also shows that for a
      given angle between the gratings there is an angle between the final grating and
      the interference plane that optimizes fringe contrast across the field.

PMID- 18709082
TI  - Standoff determination of the particle size and concentration of small optical
      depth clouds based on double scattering measurements: concept and experimental
      validation with bioaerosols.
AB  - A multiple-field-of-view (MFOV) lidar is used to characterize size and optical
      depth of low concentration of bioaerosol clouds. The concept relies on the
      measurement of the forward scattered light by using the background aerosols at
      various distances at the back of a subvisible cloud. It also relies on the
      subtraction of the background aerosol forward scattering contribution and on the
      partial attenuation of the first-order backscattering. The validity of the
      concept developed to retrieve the effective diameter and the optical depth of low
      concentration bioaerosol clouds with good precision is demonstrated using
      simulation results and experimental MFOV lidar measurements. Calculations are
      also done to show that the method presented can be extended to small optical
      depth cloud retrieval.

PMID- 18709083
TI  - Modified Fourier-Hankel method based on analysis of errors in Abel inversion
      using Fourier transform techniques.
AB  - Errors in discrete Abel inversion methods using Fourier transform techniques have
      been analyzed. The Fourier expansion method is very accurate but sensitive to
      noise. The Fourier-Hankel method has a significant systematic negative deviation,
      which increases with the radius; inversion error of the method can be reduced by
      adjusting the value of a factor. With a decrease of the factor both methods show
      a noise filtering property. Based on the analysis, a modified Fourier-Hankel
      method that is accurate, computationally efficient, and has the ability to filter
      noise in the inversion process is proposed for applying to experimental data.

PMID- 18709084
TI  - Phase-shifting interferometry with feedback control using heterodyne phase
      detection.
AB  - A phase-shifting interferometer with feedback control using heterodyne phase
      detection was developed. A composite heterodyne phase detection method for
      obtaining feedback signals was proposed. Interference fringe stabilization and
      accurate pi/2 phase shifts under micrometer-order vibrations were successfully
      demonstrated using a digital high-speed lock-in amplifier.

PMID- 18709085
TI  - Tunable Fabry-Perot-resonator-based fiber-optic white-light interferometric
      sensor array.
AB  - A tunable Fabry-Perot-resonator-based fiber-optic white-light interferometric
      quasi-distributed sensing system permitting absolute length measurement in a
      remote reflective sensor array is proposed and demonstrated. The sensor
      reflective signals characteristics have been analyzed, and the relationship
      between light signal intensities and sensors number was given for multiplexing
      potential evaluation. The proposed sensing scheme will be useful for the
      measurement of strain distribution. An important application could be deformation
      sensing in smart structures. Experimentally, a four-sensor array has been
      demonstrated.

PMID- 18709086
TI  - Diffuse reflectance spectroscopy with a self-calibrating fiber optic probe.
AB  - Calibration of the diffuse reflectance spectrum for instrument response and time
      dependent fluctuation as well as interdevice variations is complicated, time
      consuming, and potentially inaccurate. We describe a novel fiber optic probe with
      a real-time self-calibration capability that can be used for tissue optical
      spectroscopy. The probe was tested in a number of liquid phantoms over a relevant
      range of tissue optical properties. Absorption and scattering coefficients are
      extracted with an average absolute error and standard deviation of 6.9%+/-7.2%
      and 3.5%+/-1.5%, respectively.

PMID- 18709087
TI  - Unusual behavior of Tb3+ in K3YF6 green-emitting phosphor.
AB  - We report on photoluminescence studies of Tb3+ in a polycrystalline cryolite type
      K3YF6 host. The location of the Tb3+ in the center of inversion forbids the
      electric-dipole transitions of terbium ions in this material. As a consequence
      almost the entire luminescence intensity is related to the 5D4-(7)F5 magnetic
      dipole transition, and it is contained in the extremely narrow spectral bandwidth
      amounting to 1.7 nm at 8K and to 18 nm at room temperature. The phosphor under
      study can be efficiently excited making use of intense f-d transitions of Tb3+ in
      the UV-vacuum-UV region and may be of interest for applications requiring high
      spectral purity of the emission.

PMID- 18709088
TI  - Large temporal narrowing of subnanosecond pulses in a low-birefringence optical
      fiber.
AB  - A temporal shortening by a factor higher than 10 of subnanosecond pulses launched
      into a low-birefringence optical fiber is achieved by polarization filtering at
      the output. By means of the theoretical approach, in good agreement with
      experimental measurements, the impact of the nonlinear polarization rotation and
      of the coherent coupling phenomena is pointed out.

PMID- 18709089
TI  - Squeezed lattice elliptical-hole holey fiber with extremely high birefringence.
AB  - A novel highly flat elliptical-hole holey fiber with a squeezed lattice is
      introduced for achieving extremely high birefringence. The fiber consists of two
      kinds of elliptical holes with the same major axis length and different minor
      axis lengths for the core and cladding regions. Numerical results demonstrate a
      modal birefringence exceeding 0.065.

PMID- 18709090
TI  - Experimental generation of a partially coherent flat-topped beam.
AB  - An efficient optical system is proposed to generate a partially coherent flat
      topped (FT) beam theoretically. Furthermore, we report the experimental
      generation of a partially coherent FT beam based on the proposed optical system.
      The intensity distribution and the modulus of the square of the spectral degree
      of coherence of the generated partially coherent FT beam are measured. The
      experimental results are consistent with the theoretical results.

PMID- 18709091
TI  - Multisoliton ejection from an amplifying potential trap.
AB  - We study theoretically the dynamics of a beam launched inside an amplifying trap
      potential. Raising the amplification transforms the dynamics from linear
      tunneling at low amplification to periodic ejection of a sequence of identical
      solitons (when the amplification rate exceeds the tunneling rate) and, at strong
      amplification, to nonperiodic multisoliton ejection.

PMID- 18709092
TI  - Surface height retrieval based on fringe shifting of color-encoded structured
      light pattern.
AB  - A new method of fringe shifting for color structured pattern projection is
      presented for three-dimensional (3D) surface height measurement. Temporal
      encoding of color stripes is combined with locally spatial shifting of multiple
      fringes to realize image acquisition with a small number of pattern projections.
      Object topography is retrieved with high resolution by decoding the code word of
      each fringe with the help of the redundant information provided by the shifting
      patterns and the encoding patterns in their temporal and spatial neighborhoods.
      An application to evaluate the shape of a buckled tube demonstrates the
      effectiveness of the method.

PMID- 18709093
TI  - Optical phase erasure and its application to format conversion through cascaded
      second-order processes in periodically poled lithium niobate.
AB  - We describe a new optical phase erasure characteristic of periodically poled
      lithium niobate (PPLN) by using cascaded second-harmonic generation and
      difference-frequency generation with the signal set at the quasi-phase-matching
      wavelength. A simple analytical expression is derived clearly explaining the
      operation principle. It is interesting that the optical phase erasure feature
      enables an all-optical format conversion from carrier-suppressed return to zero
      (CSRZ) to return to zero (RZ). We experimentally and theoretically demonstrate a
      PPLN-based 40 Gbits/s all-optical CSRZ-to-RZ format conversion. Moreover, tunable
      and multicasting CSRZ-to-RZ format conversions are also verified in the
      experiment.

PMID- 18709094
TI  - On the role of substrate in light-harvesting experiments.
AB  - An analysis of the emitted light distribution for a single emitter located at the
      planar interface of two optical media was performed. The interface of a varying
      refractive index substrate with air was considered, which is a common case in
      luminescence microscopy (spectroscopy) experiments. A modification of the
      radiative recombination rate induced by the variation of the substrate together
      with the emitted radiation spatial redistribution were taken into account.
      Simulation results show that the collection efficiency of the emitted light can
      vary several times depending on the substrate choice and the emitter intrinsic
      quantum efficiency.

PMID- 18709095
TI  - Bistable laser operation of a Yb0.0054:Y0.3481Gd0.6465VO4 mixed crystal.
AB  - Spectroscopic properties and cw laser performance of a new
      Yb0.0054:Y0.3481Gd0.6465VO4 mixed crystal are reported. A sizable bistability is
      displayed in the laser operation with a bistability range of 1.9-3.4 W in terms
      of absorbed pump power, in which the coexistence and switching of the sigma and
      pi polarization states occur accompanied by wavelength shifting upon decreasing
      the pump power.

PMID- 18709096
TI  - Improved sectioning in a slit scanning confocal microscope.
AB  - We describe a simple implementation of a slit scanning confocal microscope to
      obtain an axial resolution better than that of a point-scanning confocal
      microscope. Under slit illumination, images of a fluorescent object are captured
      using an array detector instead of a line detector so that out-of-focus light is
      recorded and then subtracted from the adjacent images. Axial resolution after
      background subtraction is 2.2 times better than the slit confocal resolution, and
      out-of-focus image suppression is calculated to attenuate with defocus faster by
      1 order of magnitude than in the point confocal case.

PMID- 18709097
TI  - Enhancement of phosphor efficiency via composition modification.
AB  - The luminescence efficiency of Mn4+-doped CaAl12O19 (Mn:CAO) is significantly
      improved by composition modification. The leading mechanism that quenches the
      Mn4+ photoluminescence is the formation of Mn4+ pairs in the lattice of CaAl12O19
      (CAO) with interstitial O2- for charge compensation. Mixing Mg2+ ions into the
      CAO lattice may form Mn4+-Mg2+ pairs and reduce the number of Mn4+ pairs, thus
      enhancing the Mn4+ luminescence efficiency by more than three times. It is shown
      that the presence of Mg2+ leads to formation of additional phases that also
      affect the optical properties of Mn4+.

PMID- 18709098
TI  - Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination
      microscopy.
AB  - We describe a method of obtaining optical sectioning with a standard wide-field
      fluorescence microscope. The method involves acquiring two images, one with
      nonuniform illumination (in our case, speckle) and another with uniform
      illumination (in our case, randomized speckle). An evaluation of the local
      contrast in the speckle-illumination image provides an optically sectioned image
      with low resolution. This is complemented with high-resolution information
      obtained from the uniform-illumination image. A fusion of both images leads to a
      full resolution image that is optically sectioned across all spatial frequencies.
      This hybrid illumination method is fast, robust, and generalizable to a variety
      of illumination and imaging configurations.

PMID- 18709099
TI  - Lossless equalization of frequency combs.
AB  - Frequency combs obtained by sinusoidal phase modulation of narrowband cw lasers
      are widely used in the field of optical communications. However, the resulting
      spectral envelope of the comb is not flat. We propose a general and efficient
      approach to achieve flat frequency combs with tunable bandwidth. The idea is
      based on a two-step process. First, efficient generation of a train with a
      temporal flat-top-pulse profile is required. Second, we use large parabolic phase
      modulation in every train period to map the temporal intensity shape into the
      spectral domain. In this way the resulting spectral envelope is flat, and the
      size is tunable with the chirping rate. Two different schemes are proposed and
      verified through numerical simulations.

PMID- 18709100
TI  - Broadband frequency mode entanglement in waveguided parametric downconversion.
AB  - We report the observation of beatings of the coincidence event rate in a Hong-Ou
      Mandel interference (HOMI) between signal and idler photons from a parametric
      downconversion (PDC) process inside a multimode KTP waveguide. As an explanation
      we introduce biphotonic states entangled in their broadband frequency modes
      generated by waveguide mode triples and propose a suitable entanglement detection
      scheme.

PMID- 18709101
TI  - Comment on "Resolving the wave vector and the refractive index from the
      coefficient of reflectance".
AB  - In a recent Letter, the reflectance coefficient was used to resolve the sign
      choice of the wave vector and refractive index in active media. We argue that
      such a coefficient loses its physical meaning for active media (at real
      frequencies) when the field amplification is limited only by gain saturation. In
      this case, the amplitude reflectance coefficient leads to fictitious noncausal
      reflected fields when the backward Fourier transform is used.

PMID- 18709103
TI  - Collapse of optical binding under secondary irradiation.
AB  - When an optically trapped and bound micrometer-sized chain of particles is
      subjected to a suitably oriented secondary laser beam above a threshold level of
      intensity, the structure will collapse. The effect arises from modifications to
      the interparticle energy landscapes owing to the superposition of optically
      induced potentials. From the theory it also emerges that, for particles separated
      by near-field distances, optically induced assemblies may be continuously
      transformed between linear, spherical, and lamellar forms. The results show scope
      for the optical fabrication of moldable nanoscale structures.

PMID- 18709104
TI  - Ten gigabits per second 16-level quadrature amplitude modulated millimeter-wave
      carrier generation using dual-drive Mach-Zehnder modulators incorporated photonic
      vector modulator.
AB  - A novel photonic-vector modulator architecture for the generation of 16
      quadrature amplitude modulation (16 QAM) millimeter-wave carriers using dual
      drive Mach-Zehnder modulators is proposed. Experimental generation of 5 Gbits/s 4
      amplitude shift-keying (4 ASK) and 10 Gbits/s 16 QAM modulated 42 GHz carriers is
      reported. The multilevel modulated millimeter-wave signals are demodulated using
      an electrical receiver and its error-vector magnitude (EVM) estimated from the
      measurements, obtaining EVMs of -21.04 and -18.33 dB for 4 ASK and 16 QAM
      modulation formats, respectively.

PMID- 18709105
TI  - Spatially resolved trace detection of HCl in flames with mid-infrared
      polarization spectroscopy.
AB  - Sensitive and nonintrusive detection of HCl in reactive gas flows with high
      spatial and temporal resolution manner has for the first time (to our knowledge)
      been demonstrated using mid-infrared polarization spectroscopy (IRPS). Trace
      levels of HCl were prepared in an atmospheric pressure premixed CH4/O2/Ar flat
      flame by seeding a small amount of chloroform into the Ar flow. Detection of HCl
      with IRPS in the burnt region of the stoichiometric flame was performed by
      probing the fundamental ro-vibration transitions with a 3.2 microm tunable pulsed
      laser. The quantitative nature, the detection sensitivity, and the potential
      spectral interferences from water were investigated.

PMID- 18709106
TI  - Cancellation of simple optical anisotropies without use of a Faraday mirror.
AB  - We first derive the round-trip Jones matrix for double passage through a
      reciprocal optical medium by means of reflection off a plane mirror that could be
      optically anisotropic. We then show that if a medium with only linear
      birefringence and linear dichroism is placed between a pair of orthogonal quarter
      wave plates with principal axes at 45 degrees to that of the medium and the
      sandwich is placed in front of an isotropic mirror it behaves, under double
      passage, like an isotropic medium. We describe a simple liquid crystal device
      that behaves, in reflection, as an isotropic medium whose refractive index can be
      varied by application of an electric field, thus acting as a phase only modulator
      for light in any polarization state.

PMID- 18709107
TI  - Ultranarrow-bandwidth atomic filter with Raman light amplification.
AB  - A Raman-amplified atomic filter is demonstrated experimentally. With a coupling
      light detuned from the D2 line of 85Rb, a weak signal light can be amplified by a
      factor of 55, and the bandwidth of the filter's transmission spectrum is narrowed
      to approximately 60 MHz. Moreover, the transmission wavelength is adjustable by
      changing the coupling-light frequency. Compared with a conventional dispersive
      atomic filter, this Raman-amplified atomic filter could be more efficient to
      suppress background noise in free-space quantum-key distribution or a laser
      communication system.

PMID- 18709108
TI  - Auto-correction method for differential attenuation in a fiber-optic distributed
      temperature sensor.
AB  - A novel method to improve the accuracy of fiber-optic distributed-temperature
      measurements derived from Raman backscatterings is presented. This method
      utilizes two light sources with different wavelengths, such that the wavelength
      of the primary source's return anti-Stokes component overlaps with the incident
      wavelength of the secondary light source to cancel out the nonidentical
      attenuations generated by the wavelength differences between Stokes and anti
      Stokes. The concept is successfully verified by the experimental results obtained
      from several sample fibers. The correction can be made automatically and
      continuously without any interruptions during the whole measurement periods.

PMID- 18709109
TI  - Full-vector mode solver for bending waveguides based on the finite-difference
      frequency-domain method in cylindrical coordinate systems.
AB  - A full-vector mode solver for bending waveguides is described based on the finite
      difference frequency-domain method in a local cylindrical coordinate system in
      which the formulas are directly derived from Maxwell's equations with the help of
      Yee's mesh. The perfectly matched layer absorbing boundary conditions are
      incorporated into the present approach in order to effectively demonstrate the
      leaky nature of bending waveguides. A typical bending rib waveguide is considered
      as a numerical example to show the effectiveness of the established method.

PMID- 18709110
TI  - Observation of polychromatic vortex solitons.
AB  - We demonstrate experimentally the formation of polychromatic single- and double
      charge optical vortex solitons by employing a lithium niobate crystal as a
      nonlinear medium with defocusing nonlinearity. We study the wavelength dependence
      of the vortex core localization and observe self-trapping of polychromatic
      vortices with a bandwidth spanning over more than 70 nm for single-charge and 180
      nm for double-charge vortex solitons.

PMID- 18709111
TI  - Vortex characteristics of Fraunhofer diffractions of a plane wave by a spiral
      phase plate limited by pseudoring polygonal apertures.
AB  - We introduce a multilevel spiral phase plate (SPP) limited by a pseudoring
      polygonal aperture (PRPA). Such an SPP has the advantages of easier fabrication
      and greater suppression of the sidelobes of the diffraction field over that
      generated with a polygonal aperture (PA). The Fraunhofer diffraction fields
      generated by an SPP with a PRPA or with a PA have the same topological charge
      features and a similar diffraction pattern. Numerical evaluations show that the
      maximum bright annular-intensity difference between the diffraction patterns for
      the SPP with a PRPA and that of a PA does not exceed 3% under optimal design
      parameters.

PMID- 18709112
TI  - Modal expansion for J0-correlated electromagnetic sources.
AB  - We introduce a class of sources that turn out to be J0 correlated in a scalar
      description but exhibit varied correlation properties when examined in
      electromagnetic terms. We prove that a modal expansion can be built explicitly
      for any of these sources and give an example to illustrate the richness of their
      behavior.

PMID- 18709113
TI  - Analytical performance study of solar blind non-line-of-sight ultraviolet short
      range communication links.
AB  - Motivated by recent advances in solid-state incoherent ultraviolet sources and
      solar blind detectors, we study communication link performance over a range of
      less than 1 km with a bit error rate (BER) below 10(-3) in solar blind non-line
      of-sight situation. The widely adopted yet complex single scattering channel
      model is significantly simplified by means of a closed-form expression for
      tractable analysis. Path loss is given as a function of transceiver geometry as
      well as atmospheric scattering and attenuation and is compared with experimental
      data for model validation. The BER performance of a shot-noise-limited receiver
      under this channel model is demonstrated.

PMID- 18709114
TI  - Spectral anomalies near phase singularities in reflection at Brewster's angle and
      colored castastrophes.
AB  - The anomalous behavior of a polychromatic beam reflected from the interface of
      two homogeneous dielectric media at the neighborhood of Brewster's angle is
      investigated theoretically and examined experimentally. An explicit expression is
      derived for the spectrum at an arbitrary observation point for a given incident
      spectrum. By introducing a modifier function it is shown that the spectrum at
      each point sensitively depends on the observation angle just in the immediate
      neighborhood of Brewster's angle and wavelength. Finally, the obtained results
      are applied to account for the horizontal parts of the supernumerary rainbows.

PMID- 18709115
TI  - Dependence of the degree of paraxiality on field correlations.
AB  - A linearly polarized optical field can be obtained by filtering a stochastic
      field through an ideal linear polarizer. The produced field possesses a given
      degree of paraxiality that, as proved in the present Letter, can be affected by
      the correlations of the original stochastic field. An example with Gaussian beams
      is discussed in detail.

PMID- 18709116
TI  - Wavelength-scanning white-light interferometry with a 3x3 coupler-based
      interferometer.
AB  - A novel white-light interferometry capable of retrieving the absolute optical
      path difference is presented, in which a 3x3 coupler-based interferometer is
      employed. The measured phase change is in agreement with that obtained by Fourier
      transform white-light interferometry. The linear property is also experimentally
      demonstrated.

PMID- 18709117
TI  - Dual-wavelength synchronously mode-locked Nd:CNGG laser.
AB  - We have experimentally demonstrated a dual-wavelength synchronously mode-locked
      Nd:CNGG laser based on the semiconductor saturable absorber mirror technique.
      Mode locking was achieved simultaneously on two gain bands of the crystal that
      have a central wavelength separation of 2.4 nm. The fundamental mode-locked pulse
      train has a repetition rate of 88 MHz and pulse duration of 5 ps, with an average
      output power of approximately 90 mW. Autocorrelation measurements show that each
      of the synchronously mode-locked pulses consists of a train of quasi-periodic
      beat pulses with a 660 fs pulse width and a 0.63 THz repetition rate.

PMID- 18709118
TI  - Mid-infrared photoacoustic spectroscopy of solids using an external-cavity
      quantum-cascade laser.
AB  - We describe the use of a pulsed external-cavity quantum-cascade laser (EC-QCL)
      for the acquisition of mid-IR photoacoustic (PA) spectra of solids. The EC-QCL
      employed in this work operates from 990 to 1075 cm(-1) (9.30-10.10 microm). A gas
      microphone PA cell was used as the detector, and the signal was demodulated using
      a lock-in amplifier. PA EC-QCL spectra of solids display bands significantly
      narrower than those in corresponding PA Fourier transform infrared spectra.

PMID- 18709119
TI  - Directional blood flow imaging in volumetric optical microangiography achieved by
      digital frequency modulation.
AB  - An effective digital frequency modulation approach to achieve directional blood
      flow imaging within microcirculations in tissue beds in vivo for optical
      microangiography is presented. The method only requires the system to capture one
      three-dimensional data set within which the interferograms are modulated by a
      constant frequency modulation that gives one directional flow information. The
      result is that the imaging speed is doubled and the computational load is halved.
      The method is experimentally validated by a flow phantom and is tested for
      imaging of cerebral vascular blood perfusion in a live mouse with the cranium
      left intact.

PMID- 18709120
TI  - Interchip link system using an optical wiring method.
AB  - A chip-scale optical link system is presented with a transmitter/receiver and
      optical wire link. The interchip link system consists of a metal optical bench, a
      printed circuit board module, a driver/receiver integrated circuit, a vertical
      cavity surface-emitting laser/photodiode array, and an optical wire link composed
      of plastic optical fibers (POFs). We have developed a downsized POF and an
      optical wiring method that allows on-site installation with a simple annealing as
      optical wiring technologies for achieving high-density optical interchip
      interconnection within such devices. Successful data transfer measurements are
      presented.

PMID- 18709121
TI  - Near-infrared quantum cutting in transparent nanostructured glass ceramics.
AB  - Quantum cutting downconversion involving the emission of two near-infrared
      photons for each blue photon absorbed is realized in transparent glass ceramics
      with embedded Pr3+/Yb3+: beta-YF3 nanocrystals. On excitation of Pr3+ ions with a
      visible photon at 482 nm, Yb3+ ions emit two near-infrared photons at 976 nm
      through an efficient cooperative energy transfer from Pr3+ to Yb3+, with optimal
      quantum efficiency close to 200%. The development of the near-infrared quantum
      cutting transparent glass ceramic could open a route to enhance the energy
      efficiency of the silicon solar cell by converting one blue solar photon to two
      near-infrared ones.

PMID- 18709122
TI  - Three-dimensional molecular mapping in a microfluidic mixing device using
      fluorescence lifetime imaging.
AB  - Fluorescence lifetime imaging (FLIM) is used to quantitatively map the
      concentration of a small molecule in three dimensions in a microfluidic mixing
      device. The resulting experimental data are compared with computational fluid
      dynamics (CFD) simulations. A line-scanning semiconfocal FLIM microscope allows
      the full mixing profile to be imaged in a single scan with submicrometer
      resolution over an arbitrary channel length from the point of confluence.
      Following experimental and CFD optimization, mixing times down to 1.3+/-0.4 ms
      were achieved with the single-layer microfluidic device.

PMID- 18709123
TI  - Droplet deformation and alignment for high-efficiency polarization-dependent
      holographic polymer-dispersed liquid-crystal reflection gratings.
AB  - Droplet deformation and alignment are achieved in holographic polymer-dispersed
      liquid-crystal reflection gratings by applying an in situ shear during recording.
      High diffraction efficiency (99%) is obtained for light polarized parallel to the
      shear, with nearly zero efficiency for perpendicular polarization, and no
      increase of incoherent scattering. Permanent polarization dependence is related
      to stress-induced morphology changes of liquid-crystal droplets that are frozen
      by polymerization. The system is studied by electron microscopy and modeled by
      anisotropic coupled-wave and scattering theory. The morphology is consistent with
      the theory of small deformations of liquid droplets in fluid flow. Diffraction
      efficiency measurements are in agreement with theory incorporating this
      morphology as well as concomitant orientation and alignment of liquid-crystal
      molecules.

PMID- 18709124
TI  - In situ accurate determination of the zero time delay between two independent
      ultrashort laser pulses by observing the oscillation of an atomic excited wave
      packet.
AB  - We propose a novel method that uses the oscillation of an atomic excited wave
      packet observed through a pump-probe technique to accurately determine the zero
      time delay between a pair of ultrashort laser pulses. This physically based
      approach provides an easy fix for the intractable problem of synchronizing two
      different femtosecond laser pulses in a practical experimental environment,
      especially where an in situ time zero measurement with high accuracy is required.

PMID- 18709125
TI  - Self-phase-locked degenerate femtosecond optical parametric oscillator.
AB  - We demonstrated a stable degenerate synchronously pumped femtosecond optical
      parametric oscillator (SPOPO) as a divide-by-2 subharmonic generator. The SPOPO
      exhibited passive all-optical self-phase-locking between the pump and
      signal/idler and thus required no external electronic feedback to produce the
      phase-locked subharmonic. We employed a type I phase-matched, 1-mm-long,
      periodically poled MgO:LiNbO3 crystal as the nonlinear gain element and an 80 MHz
      mode-locked Ti:sapphire laser with 180 fs pulses tuned at 775 nm as the pump. The
      SPOPO generated transform-limited 70 fs phase-locked output pulses centered at
      1550 nm. The self-phase-locking operation was confirmed by separate beat-note
      measurement techniques with respect to the pump laser and with respect to an
      external cw laser.

PMID- 18709126
TI  - Solving the phase-retrieval problem of a complex signal in the fractional Fourier
      domain by nonlinear least-squares.
AB  - From the viewpoint of unconstrained optimization the phase-retrieval problem of a
      1D complex signal in the fractional Fourier domain is formulated as a nonlinear
      least-squares problem. A definition of the discrete fractional Fourier transform
      (DFRFT) constructed by a discrete Hermite-Gaussian function is adopted here. The
      ill-posedness of the problem is stressed, and the Levenberg-Marquardt algorithm
      of More's form is used to solve it. In contrast to many published references,
      this method can reconstruct the phase accurately from the amplitude of the
      original signal and the one of its DFRFT at any order in the interval (0, 2). For
      amplitudes with low-level noise this method also works well.

PMID- 18709127
TI  - Split-aperture laser pulse compressor design tolerant to alignment and line
      density differences.
AB  - We introduce a four-pass laser pulse compressor design based on two grating
      apertures with two gratings per aperture that is tolerant to some alignment
      errors and, importantly, to grating-to-grating period variations. Each half-beam
      samples each grating in a diamond-shaped compressor that is symmetric about a
      central bisecting plane. For any given grating, the two half-beams impinge on
      opposite sides of its surface normal. It is shown that the two split beams have
      no pointing difference from paired gratings with different periods. Furthermore,
      no phase shift between half-beams is incurred as long as the planes containing a
      grating line and the surface normal for each grating of the pair are parallel.
      For grating pairs satisfying this condition, gratings surfaces need not be on the
      same plane, as changes in the gap between the two can compensate to bring the
      beams back in phase.

PMID- 18709128
TI  - Passively mode-locked 10 GHz femtosecond Ti:sapphire laser.
AB  - We report a mode-locked Ti:sapphire femtosecond laser emitting 42 fs pulses at a
      10 GHz repetition rate. When operated with a spectrally integrated average power
      greater than 1 W, the associated femtosecond laser frequency comb contains
      approximately 500 modes, each with power exceeding 1 mW. Spectral broadening in
      nonlinear microstructured fiber yields comb elements with individual powers
      greater than 1 nW over approximately 250 nm of spectral bandwidth. The modes of
      the emitted comb are resolved and imaged with a simple grating spectrometer and
      digital camera. Combined with absorption spectroscopy of rubidium vapor, this
      approach permits identification of the mode index and measurement of the carrier
      envelope offset frequency of the comb.

PMID- 18709129
TI  - GaAs photonic crystal cavity with ultrahigh Q: microwatt nonlinearity at 1.55
      microm.
AB  - We haves realized and measured a GaAs nanocavity in a slab photonic crystal based
      on the design by Kuramochi et al. [Appl. Phys. Lett. 88, 041112 (2006)]. We
      measure a quality factor Q=700,000, which proves that ultrahigh Q nanocavities
      are also feasible in GaAs. We show that owing to larger two-photon absorption in
      GaAs nonlinearities appear at the microwatt level and will be more functional in
      gallium arsenide than in silicon nanocavities.

PMID- 18709130
TI  - Electromagnetically induced transparency-like effect in the degenerate triple
      resonant optical parametric amplifier.
AB  - We investigate experimentally the absorptive and dispersive properties of the
      triple-resonant optical parametric amplifier (OPA) for the degenerate subharmonic
      field. In the experiment the subharmonic field is utilized as the probe field and
      the harmonic wave as the pump field. We demonstrate that the electromagnetically
      induced transparency (EIT)-like effect can be simulated in the triple-resonant
      OPA when the cavity linewidth for the harmonic wave is narrower than that for the
      subharmonic field. However, this phenomenon cannot be observed in a double
      resonant OPA. The narrow transparency window appears in the reflected field.
      Especially in the measured dispersive spectra of the triple-resonant OPA, a very
      steep variation of the dispersive profile of the subharmonic field is observed,
      which can result in a slow light as that observed in an atomic EIT medium.

PMID- 18709131
TI  - Excitation and detection of surface-plasmon polariton waves on Cu(111) with
      gratings of rare gas monolayers.
AB  - We excited surface-plasmon polariton waves (SPPWs) on Cu(111) by coupling optical
      beams with adsorbed xenon gratings. The SPPWs's excitation causes a resonancelike
      dip in the angle-resolved reflectivity difference measurement. From the resonance
      we determined optical constants epsilonCu(633 nm)=-9.53+i0.142 and epsilonCu(780
      nm)=-13.44+i0.18. The grating-coupled SPPWs can be used to study mass transport
      on thin films.

PMID- 18709132
TI  - Ultrahigh-temperature regenerated gratings in boron-codoped germanosilicate
      optical fiber using 193 nm.
AB  - Regenerated gratings seeded by type I gratings in boron-codoped germanosilicate
      optical fiber written with 193 nm are shown to withstand temperatures beyond 1000
      degrees C.

PMID- 18709133
TI  - Frequency-modulated, tunable, semiconductor-optical-amplifier-based fiber ring
      laser for linewidth and line shape control.
AB  - We report how the linewidth and line shape of a tunable semiconductor-optical
      amplifier-based fiber ring laser can be actively adjusted by applying an
      intracavity frequency modulation to the laser. Frequency-modulated laser
      operation is achieved by driving the phase modulator frequency close to the
      cavity axial-mode spacing, leading to a constant-amplitude laser output having a
      periodically varying instantaneous frequency. The resulting linewidth varies
      proportionally with the inverse of the frequency detuning, and it is adjustable
      from submegahertz to over more than 5 GHz. By appropriate selection of the
      modulating waveform we have synthesized a near-Gaussian output line shape; other
      line shapes can be produced by modifying the modulating waveform. Experimental
      observations are in good agreement with a simple model.

PMID- 18709135
TI  - Anisotropic hinge model for polarization-mode dispersion in installed fibers.
AB  - We discuss a generalized waveplate hinge model to characterize anisotropic
      effects associated with the hinge model of polarization-mode dispersion in
      installed systems. In this model, the action of the hinges is a random time
      dependent rotation about a fixed axis. We obtain the probability density function
      of the differential group delay and the outage probability of an individual
      wavelength band using a combination of importance sampling and the cross-entropy
      method, and we then compute the noncompliant capacity ratio by averaging over
      wavelength bands. The results show that there are significant differences between
      the outage statistics predicted by isotropic and anisotropic hinge models.

PMID- 18709136
TI  - Visibility of surgical site marking after preoperative skin preparation.
AB  - OBJECTIVE: It is important that during preoperative skin preparation surgical
      site markings are not erased. The effects of 2 common types of skin preparation
      solutions on surgical site markings were compared. METHODS: Fasciocutaneous skin
      flaps were harvested and 20 random combinations of 3 letters were written on the
      skin flaps with a black permanent marker. Ten of the 3-letter combinations
      received Chloraprep (chlorhexidine gluconate, 2% w/v, plus isopropyl alcohol, 70%
      v/v) and the other 10 received Duraprep (iodine povacrylex [0.7% available
      iodine] and isopropyl alcohol [74% w/w]), both according to the manufacturer's
      guidelines. The skin flaps were photographed digitally before and after
      application of the solutions. The final pictures were assessed subjectively by 10
      surgeons and then objectively to determine the change in visibility of the
      marking on each specimen. RESULTS: Of the 300 letters in each group, the number
      of correctly identified letters was 254 (84.7%) in the Chloraprep group and 284
      (94.7%) in the Duraprep group. On the basis of the visibility of skin markings,
      Chloraprep was 21.8 times more likely (95% credible interval, 7.3-86.7) to erase
      the site markings than was Duraprep. CONCLUSIONS: Skin preparation with
      Chloraprep erased more surgical site markings than did Duraprep.

PMID- 18709137
TI  - Lowered cortistatin expression is an early event in the human diabetic retina and
      is associated with apoptosis and glial activation.
AB  - PURPOSE: Cortistatin (CST), a neuropeptide with strong structural and functional
      similarities to somatostatin, is abundant in the vitreous fluid, and it is
      decreased in patients with proliferative diabetic retinopathy. The aims of the
      present study were to explore whether the retina produces CST, and to compare its
      expression between diabetic and nondiabetic donors. Retinal neurodegeneration was
      assessed by measuring glial fibrilar acidic protein (GFAP) by confocal laser
      microscopy and counting the apoptotic TUNEL positive cells in which nuclear
      fragmentation as well as condensation were present. METHODS: Human postmortem
      eyes (10) from five diabetic donors were compared with 10 eyes from five
      nondiabetic donors, matched by age. CST mRNA (RT-PCR) and CST (confocal laser
      microscopy) were measured separately in both the neuroretina and retinal pigment
      epithelium (RPE). Retinal neurodegeneration was assessed by measuring glial
      fibrillar acidic protein (GFAP) by confocal laser microscopy and counting the
      apoptotic cells by TUNEL. RESULTS: CST was found to be produced by the human
      retina, and higher levels of CST mRNA were found in RPE than in the neuroretina.
      CST mRNA levels in diabetic donors were significantly lower in both the RPE
      (p=0.001) and the neuroretina (p=0.03) in comparison with nondiabetic donors. CST
      immunofluorescence was in agreement with mRNA expression, but the differences
      were only significant when comparing neuroretinas (p=0.03). Increased GFAP and a
      higher degree of apoptosis were observed in diabetic retinas in comparison with
      nondiabetic retinas. These changes were inversely related with CST levels.
      CONCLUSIONS: CST is expressed in the human retina. There is more CST in the RPE
      than in the neuroretina. A lower expression of CST exists in diabetic retinas and
      it is associated with retinal neurodegeneration.

PMID- 18709138
TI  - Computational toxicology of chloroform: reverse dosimetry using Bayesian
      inference, Markov chain Monte Carlo simulation, and human biomonitoring data.
AB  - BACKGROUND: One problem of interpreting population-based biomonitoring data is
      the reconstruction of corresponding external exposure in cases where no such data
      are available. OBJECTIVES: We demonstrate the use of a computational framework
      that integrates physiologically based pharmacokinetic (PBPK) modeling, Bayesian
      inference, and Markov chain Monte Carlo simulation to obtain a population
      estimate of environmental chloroform source concentrations consistent with human
      biomonitoring data. The biomonitoring data consist of chloroform blood
      concentrations measured as part of the Third National Health and Nutrition
      Examination Survey (NHANES III), and for which no corresponding exposure data
      were collected. METHODS: We used a combined PBPK and shower exposure model to
      consider several routes and sources of exposure: ingestion of tap water,
      inhalation of ambient household air, and inhalation and dermal absorption while
      showering. We determined posterior distributions for chloroform concentration in
      tap water and ambient household air using U.S. Environmental Protection Agency
      Total Exposure Assessment Methodology (TEAM) data as prior distributions for the
      Bayesian analysis. RESULTS: Posterior distributions for exposure indicate that
      95% of the population represented by the NHANES III data had likely chloroform
      exposures < or = 67 microg/L [corrected] in tap water and < or = 0.02 microg/L in
      ambient household air. CONCLUSIONS: Our results demonstrate the application of
      computer simulation to aid in the interpretation of human biomonitoring data in
      the context of the exposure-health evaluation-risk assessment continuum. These
      results should be considered as a demonstration of the method and can be improved
      with the addition of more detailed data.

PMID- 18709139
TI  - Methodologic issues and approaches to spatial epidemiology.
AB  - Spatial epidemiology is increasingly being used to assess health risks associated
      with environmental hazards. Risk patterns tend to have both a temporal and a
      spatial component; thus, spatial epidemiology must combine methods from
      epidemiology, statistics, and geographic information science. Recent statistical
      advances in spatial epidemiology include the use of smoothing in risk maps to
      create an interpretable risk surface, the extension of spatial models to
      incorporate the time dimension, and the combination of individual- and area-level
      information. Advances in geographic information systems and the growing
      availability of modeling packages have led to an improvement in exposure
      assessment. Techniques drawn from geographic information science are being
      developed to enable the visualization of uncertainty and ensure more meaningful
      inferences are made from data. When public health concerns related to the
      environment arise, it is essential to address such anxieties appropriately and in
      a timely manner. Tools designed to facilitate the investigation process are being
      developed, although the availability of complete and clean health data, and
      appropriate exposure data often remain limiting factors.

PMID- 18709140
TI  - Integrating human health into environmental impact assessment: an unrealized
      opportunity for environmental health and justice.
AB  - OBJECTIVES: The National Environmental Policy Act and related state laws require
      many public agencies to analyze and disclose potentially significant
      environmental effects of agency actions, including effects on human health. In
      this paper we review the purpose and procedures of environmental impact
      assessment (EIA), existing regulatory requirements for health effects analysis,
      and potential barriers to and opportunities for improving integration of human
      health concerns within the EIA process. DATA SOURCES: We use statutes,
      regulations, guidelines, court opinions, and empirical research on EIA along with
      recent case examples of integrated health impact assessment (HIA)/EIA at both the
      state and federal level. DATA SYNTHESIS: We extract lessons and recommendations
      for integrated HIA/EIA practice from both existing practices as well as case
      studies. CONCLUSIONS: The case studies demonstrate the adequacy, scope, and power
      of existing statutory requirements for health analysis within EIA. The following
      support the success of integrated HIA/EIA: a proponent recognizing EIA as an
      available regulatory strategy for public health; the openness of the agency
      conducting the EIA; involvement of public health institutions; and complementary
      objectives among community stakeholders and health practitioners. We recommend
      greater collaboration among institutions responsible for EIA, public health
      institutions, and affected stakeholders along with guidance, resources, and
      training for integrated HIA/EIA practice.

PMID- 18709141
TI  - Comparison of different methods for spatial analysis of cancer data in Utah.
AB  - BACKGROUND: The standardized incidence ratio (SIR) and SaTScan software are used
      by the Environmental Epidemiology Program (EEP), Utah Department of Health, to
      investigate health concerns and exposures in Utah (USA). Recently, the EEP
      acquired the Rapid Inquiry Facility (RIF). The RIF enables access of additional
      dimensions of data, identifies potentially exposed populations, and computes
      disease rates and relative risk statistics for that potentially exposed
      population. OBJECTIVE: In this article we present a comparison of the SIR,
      SaTScan, and RIF methodologies in an investigation of cancer rates in residents
      living over contaminated groundwater plumes near Hill Air Force Base (HAFB) in
      Utah. METHODS: For this study, we used cancer data from the Utah Cancer Registry
      for cancers of the lung, kidney, and non-Hodgkin lymphoma. We used SIR and the
      RIF to investigate the cancer rate in a defined population within the study area
      during six consecutive 5-year time intervals (1975-2004). We used SaTScan and the
      RIF to explore the study area for clusters. RESULTS: The RIF risk analysis and
      SIR are mathematically identical. SIR is set up and computed by programming SAS;
      the RIF risk analysis, on the other hand, is set up through four menu-driven
      steps. The RIF disease-mapping feature enhanced the interpretation of SaTScan
      results. We found kidney and lung cancer to be statistically elevated for the
      potentially exposed population for one and two periods, respectively. SaTScan
      found two clusters, one outside the potentially exposed population and one that
      included a portion of that population. CONCLUSION: The RIF is an easy-to-use and
      useful tool that extends the ability of the investigator to conduct analysis of
      disease rates and interpret the findings.

PMID- 18709143
TI  - Use of space-time models to investigate the stability of patterns of disease.
AB  - BACKGROUND: The use of Bayesian hierarchical spatial models has become widespread
      in disease mapping and ecologic studies of health-environment associations. In
      this type of study, the data are typically aggregated over an extensive time
      period, thus neglecting the time dimension. The output of purely spatial disease
      mapping studies is therefore the average spatial pattern of risk over the period
      analyzed, but the results do not inform about, for example, whether a high
      average risk was sustained over time or changed over time. OBJECTIVE: We
      investigated how including the time dimension in disease-mapping models
      strengthens the epidemiologic interpretation of the overall pattern of risk.
      METHODS: We discuss a class of Bayesian hierarchical models that simultaneously
      characterize and estimate the stable spatial and temporal patterns as well as
      departures from these stable components. We show how useful rules for classifying
      areas as stable can be constructed based on the posterior distribution of the
      space-time interactions. We carry out a simulation study to investigate the
      sensitivity and specificity of the decision rules we propose, and we illustrate
      our approach in a case study of congenital anomalies in England. RESULTS: Our
      results confirm that extending hierarchical disease-mapping models to models that
      simultaneously consider space and time leads to a number of benefits in terms of
      interpretation and potential for detection of localized excesses.

PMID- 18709144
TI  - Adverse cardiovascular effects with acute particulate matter and ozone exposures:
      interstrain variation in mice.
AB  - OBJECTIVES: Increased ambient particulate matter (PM) levels are associated with
      cardiovascular morbidity and mortality, as shown by numerous epidemiology
      studies. Few studies have investigated the role of copollutants, such as ozone,
      in this association. Furthermore, the mechanisms by which PM affects cardiac
      function remain uncertain. We hypothesized that PM and O(3) induce adverse
      cardiovascular effects in mice and that these effects are strain dependent. STUDY
      DESIGN: After implanting radiotelemeters to measure heart rate (HR) and HR
      variability (HRV) parameters, we exposed C57Bl/6J (B6), C3H/HeJ (HeJ), and
      C3H/HeOuJ (OuJ) inbred mouse strains to three different daily exposures of
      filtered air (FA), carbon black particles (CB), or O(3) and CB sequentially
      [O(3)CB; for CB, 536 +/- 24 microg/m(3); for O(3), 584 +/- 35 ppb (mean +/- SE)].
      RESULTS: We observed significant changes in HR and HRV in all strains due to
      O(3)CB exposure, but not due to sequential FA and CB exposure (FACB). The data
      suggest that primarily acute HR and HRV effects occur during O(3)CB exposure,
      especially in HeJ and OuJ mice. For example, HeJ and OuJ mice demonstrated
      dramatic increases in HRV parameters associated with marked brady-cardia during
      O(3)CB exposure. In contrast, depressed HR responses occurred in B6 mice without
      detectable changes in HRV parameters. CONCLUSIONS: These findings demonstrate
      that important interstrain differences exist with respect to PM- and O(3)-induced
      cardiac effects. This interstrain variation suggests that genetic factors may
      modulate HR regulation in response to and recuperation from acute copollutant
      exposures.

PMID- 18709146
TI  - Floral scents going off the air?

PMID- 18709147
TI  - The global sweep of pollution: satellite snapshots capture long-distance
      movement.

PMID- 18709149
TI  - Maternal and gestational risk factors for hypospadias.
AB  - BACKGROUND: An increase in the prevalence of hypospadias has been reported, but
      the environmental causes remain virtually unknown. OBJECTIVES: Our goal was to
      assess the association between risk of hypospadias and indicators of placental
      function and endogenous hormone levels, exposure to exogenous hormones, maternal
      diet during pregnancy, and other environmental factors. METHODS: We conducted a
      case-control study in Sweden and Denmark from 2000 through 2005 using self
      administered questionnaires completed by mothers of hypospadias cases and matched
      controls. The response rate was 88% and 81% among mothers of cases and controls,
      respectively. The analyses included 292 cases and 427 controls. RESULTS: A diet
      during pregnancy lacking both fish and meat was associated with a more than 4
      fold increased risk of hypospadias [odds ratio (OR) = 4.6; 95% confidence
      interval (CI), 1.6-13.3]. Boys born to obese [body mass index (BMI) > or = 30]
      women had a more than 2-fold increased risk of hypospadias (OR = 2.6; 95% CI, 1.2
      5.7) compared with boys born to mothers with a normal weight (BMI = 20-24).
      Maternal hypertension during pregnancy and absence of maternal nausea increased a
      boy's risk of hypospadias 2.0-fold (95% CI, 1.1-3.7) and 1.8-fold (95% CI, 1.2
      2.8), respectively. Nausea in late pregnancy also appeared to be positively
      associated with hypospadias risk (OR = 7.6; 95% CI, 1.1-53). CONCLUSIONS: A
      pregnancy diet lacking meat and fish appears to increase the risk of hypospadias
      in the offspring. Other risk associations were compatible with a role for
      placental insufficiency in the etiology of hypospadias.

PMID- 18709148
TI  - Genomic profiling reveals an alternate mechanism for hepatic tumor promotion by
      perfluorooctanoic acid in rainbow trout.
AB  - BACKGROUND: Perfluorooctanoic acid (PFOA) is a potent hepatocarcinogen and
      peroxisome proliferator (PP) in rodents. Humans are not susceptible to peroxisome
      proliferation and are considered refractory to carcinogenesis by PPs. Previous
      studies with rainbow trout indicate they are also insensitive to peroxisome
      proliferation by the PP dehydroepiandrosterone (DHEA), but are still susceptible
      to enhanced hepatocarcinogenesis after chronic exposure. OBJECTIVES: In this
      study, we used trout as a unique in vivo tumor model to study the potential for
      PFOA carcinogenesis in the absence of peroxisome proliferation compared with the
      structurally diverse PPs clofibrate (CLOF) and DHEA. Mechanisms of carcinogenesis
      were identified from hepatic gene expression profiles phenotypically anchored to
      tumor outcome. METHODS: We fed aflatoxin B(1) or sham-initiated animals 200-1,800
      ppm PFOA in the diet for 30 weeks for tumor analysis. We subsequently examined
      gene expression by cDNA array in animals fed PFOA, DHEA, CLOF, or 5 ppm 17beta
      estradiol (E(2), a known tumor promoter) in the diet for 14 days. RESULTS: PFOA
      (1,800 ppm or 50 mg/kg/day) and DHEA treatments resulted in enhanced liver tumor
      incidence and multiplicity (p < 0.0001), whereas CLOF showed no effect.
      Carcinogenesis was independent of peroxisome proliferation, measured by lack of
      peroxisomal beta-oxidation and catalase activity. Alternately, both tumor
      promoters, PFOA and DHEA, resulted in estrogenic gene signatures with strong
      correlation to E(2) by Pearson correlation (R = 0.81 and 0.78, respectively),
      whereas CLOF regulated no genes in common with E(2). CONCLUSIONS: These data
      suggest that the tumor-promoting activities of PFOA in trout are due to novel
      mechanisms involving estrogenic signaling and are independent of peroxisome
      proliferation.

PMID- 18709150
TI  - Pentachlorophenol and cancer risk: focusing the lens on specific chlorophenols
      and contaminants.
AB  - OBJECTIVE: Pentachlorophenol, a fungicide widely used as a wood preservative, was
      classified in 1999 by the International Agency for Research on Cancer as a
      possible human carcinogen. We reviewed currently available data to determine the
      extent to which recent studies assist in distinguishing the effect of
      pentachlorophenol from that of its contaminants (e.g., dioxins and other
      chlorophenols). DATA SOURCES AND EXTRACTION: We performed a systematic review of
      published studies pertaining to cancer risk in relation to pentachlorophenol
      exposure, focusing on results pertaining specifically to all cancer sites and
      specific hematopoietic cancers, and data pertaining to risks associated with
      other types of chlorophenols, dioxins, or furans. SYNTHESIS: The
      pentachlorophenol studies presented considerable evidence pertaining to
      hematopoietic cancers, with strong associations seen in multiple studies, in
      different locations, and using different designs. There is little evidence of an
      association between these cancers and chlorophenols that contain fewer than four
      chlorines. The extension of a large cohort study of sawmill workers, with follow
      up to 1995, provided information about risks of relatively rare cancers (e.g.,
      non-Hodgkin lymphoma, multiple myeloma), using a validated exposure assessment
      procedure that distinguishes between exposures to pentachlorophenol and
      tetrachlorophenol. In contrast with dioxin, pentachlorophenol exposure has not
      been associated with total cancer incidence or mortality. CONCLUSIONS: The
      updated cohort study focusing on pentachlorophenol provides increased statistical
      power and precision, and demonstrates associations between hematopoietic cancer
      and pentachlorophenol exposure not observed in earlier evaluations of this
      cohort. Contaminant confounding is an unlikely explanation for the risks seen
      with pentachlorophenol exposure.

PMID- 18709151
TI  - Effects of exposure to 0.06 ppm ozone on FEV1 in humans: a secondary analysis of
      existing data.
AB  - BACKGROUND: Ozone is a potent photochemical oxidant that produces transient,
      reversible decrements in the lung function of acutely exposed individuals. A
      recent study provided previously unavailable clinical data for 30 healthy young
      adults exposed to O(3) at 0.06 ppm. That study showed significant effects of 0.08
      ppm on lung function, confirming the findings of others. However, exposure to
      0.06 ppm O(3) was not reported to significantly affect lung function. OBJECTIVES:
      We conducted this analysis to reevaluate the existing lung function data of the
      volunteers previously exposed to 0.06 ppm O(3). METHODS: We obtained pre- and
      postexposure data on forced expiratory volume in 1 sec (FEV(1)) for all subjects
      who were previously exposed for 6.6 hr to filtered air or to 0.06 ppm or 0.08 ppm
      O(3). We used standard statistical methods appropriate for paired comparisons to
      reanalyze FEV(1) responses after exposure to 0.06 ppm O(3) relative to filtered
      air. RESULTS: Controlling for filtered air responses, 24 of the 30 subjects
      experienced an O(3)-induced decrement in FEV(1). On average, 0.06 ppm O(3)
      exposure caused a 2.85% reduction in FEV(1) (p < 0.002), which was consistent
      with the predicted FEV(1) response from existing models. Although the average
      response was small, two subjects had > 10% FEV(1) decrements. CONCLUSIONS:
      Exposure to 0.06 ppm O(3) causes a biologically small but highly statistically
      significant decrease in mean FEV(1) responses of young healthy adults.

PMID- 18709152
TI  - Nano-food chain link examined.

PMID- 18709153
TI  - Diet and nondiet predictors of urinary 3-phenoxybenzoic acid in NHANES 1999-2002.
AB  - BACKGROUND: 3-Phenoxybenzoic acid (3PBA), a pyrethroid metabolite, was detected
      in 75% of urine samples analyzed for pesticides in the U.S. National Health and
      Nutrition Examination Survey (NHANES) 1999-2002. NHANES also includes 24-hr diet
      data and information on household pesticide use, activities, occupation,
      demographics, and other exposure factors. OBJECTIVES: The objective of our study
      was to explore the relative importance of diet versus nondiet predictors in
      explaining variability in urinary 3PBA. A secondary objective was to explore
      whether the NHANES data could be used to identify particular foods driving 3PBA
      levels. METHODS: We divided subjects into child (6-10 years of age), teen (11-18
      years), and adult (> or = 19 years) age groups and restricted our analyses to
      subjects in the morning sampling session who fasted for > or = 8 hr beforehand.
      Regression modeling consisted of several model-building steps and a final Tobit
      regression on the left-censored log 3PBA measurements. We also conducted
      bootstrap analyses to evaluate the stability of the regression parameters.
      RESULTS: Reported household pesticide use was not significantly associated with
      urinary 3PBA in any age group. Diet was significant for all three groups, and
      certain foods appeared to contribute more than others. Among adults, tobacco use
      was positively associated with 3PBA (p = 0.0326), and positive associations were
      suggested with the number of cytochrome p450-inhibiting medications taken (p =
      0.0652) and minutes spent gardening (p = 0.0613) in the past month. CONCLUSIONS:
      Although exploratory, our findings underline the importance of collecting
      accurate data on household pesticide use and dietary intake when evaluating
      pyrethroid exposure-biomarker relationships.

PMID- 18709154
TI  - In search of a better mosquito repellent.

PMID- 18709155
TI  - Defective spermatogenesis in cryptorchid testes: cause or effect?

PMID- 18709158
TI  - Recovering the good earth: China's growing organic market.

PMID- 18709157
TI  - Prenatal phenol and phthalate exposures and birth outcomes.
AB  - BACKGROUND: Many phthalates and phenols are hormonally active and are suspected
      to alter the course of development. OBJECTIVE: We investigated prenatal exposures
      to phthalate and phenol metabolites and their associations with body size
      measures of the infants at birth. METHODS: We measured 5 phenol and 10 phthalate
      urinary metabolites in a multiethnic cohort of 404 women in New York City during
      their third trimester of pregnancy and recorded size of infants at birth.
      RESULTS: Median urinary concentrations were > 10 microg/L for 2 of 5 phenols and
      6 of 10 phthalate monoester metabolites. Concentrations of low-molecular-weight
      phthalate monoesters (low-MWP) were approximately 5-fold greater than those of
      high-molecular-weight metabolites. Low-MWP metabolites had a positive association
      with gestational age [0.97 day gestational age per ln-biomarker; 95% confidence
      interval (CI), 0.07-1.9 days, multivariate adjusted] and with head circumference.
      Higher prenatal exposures to 2,5-dichlorophenol (2,5-DCP) predicted lower birth
      weight in boys (-210 g average birth weight difference between the third tertile
      and first tertile of 2,5-DCP; 95% CI, 71-348 g). Higher maternal benzophenone-3
      (BP3) concentrations were associated with a similar decrease in birth weight
      among girls but with greater birth weight in boys. CONCLUSIONS: We observed a
      range of phthalate and phenol exposures during pregnancy in our population, but
      few were associated with birth size. The association of 2,5-DCP and BP3 with
      reduced or increased birth weight could be important in very early or small-size
      births. In addition, positive associations of urinary metabolites with some
      outcomes may be attributable partly to unresolved confounding with maternal
      anthropometric factors.

PMID- 18709160
TI  - Interactions between glutathione S-transferase P1, tumor necrosis factor, and
      traffic-related air pollution for development of childhood allergic disease.
AB  - BACKGROUND: Air pollutants may induce airway inflammation and sensitization due
      to generation of reactive oxygen species. The genetic background to these
      mechanisms could be important effect modifiers. OBJECTIVE: Our goal was to assess
      interactions between exposure to air pollution and single nucleotide
      polymorphisms (SNPs) in the beta2-adrenergic receptor (ADRB2), glutathione S
      transferase P1 (GSTP1), and tumor necrosis factor (TNF) genes for development of
      childhood allergic disease. METHODS: In a birth cohort originally of 4,089
      children, we assessed air pollution from local traffic using nitrogen oxides
      (traffic NO(x)) as an indicator based on emission databases and dispersion
      modeling and estimated individual exposure through geocoding of home addresses.
      We measured peak expiratory flow rates and specific IgE for inhalant and food
      allergens at 4 years of age, and selected children with asthma symptoms up to 4
      years of age (n = 542) and controls (n = 542) for genotyping. RESULTS:
      Interaction effects on allergic sensitization were indicated between several
      GSTP1 SNPs and traffic NO(x) exposure during the first year of life (p(nominal) <
      0.001-0.06). Children with Ile105Val/Val105Val genotypes were at increased risk
      of sensitization to any allergen when exposed to elevated levels of traffic NO(x)
      (for a difference between the 5th and 95th percentile of exposure: odds ratio =
      2.4; 95% confidence interval, 1.0-5.3). In children with TNF-308 GA/AA genotypes,
      the GSTP1-NO(x) interaction effect was even more pronounced. We observed no
      conclusive interaction effects for ADRB2. CONCLUSION: The effect of air pollution
      from traffic on childhood allergy appears to be modified by GSTP1 and TNF
      variants, supporting a role of genes controlling the antioxidative system and
      inflammatory response in allergy.

PMID- 18709161
TI  - Estimating community drug abuse by wastewater analysis.
AB  - BACKGROUND: The social and medical problems of drug abuse are a matter of
      increasing global concern. To tackle drug abuse in changing scenarios,
      international drug agencies need fresh methods to monitor trends and patterns of
      illicit drug consumption. OBJECTIVE: We tested a sewage epidemiology approach,
      using levels of excreted drug residues in wastewater, to monitor collective use
      of the major drugs of abuse in near real time. METHODS: Selected drug target
      residues derived from use of cocaine, opiates, cannabis, and amphetamines were
      measured by mass spectrometry in wastewater collected at major sewage treatment
      plants in Milan (Italy), Lugano (Switzerland), and London (United Kingdom). The
      amounts of drug residues conveyed to the treatment plants, reflecting the amounts
      collectively excreted with urine, were used to estimate consumption of the active
      parent drugs. RESULTS: Reproducible and characteristic profiles of illicit drug
      use were obtained in the three cities, thus for the first time quickly revealing
      changes in local consumption (e.g., cocaine consumption rose significantly on
      weekends in Milan). Profiles of local drug consumption based on waste-water
      measurements are in line with national annual prevalence estimates. CONCLUSIONS:
      Patterns and trends of drug abuse in local communities can be promptly monitored
      by this tool, a convenient new complement to more complex, lengthy survey
      methods. In principle, searching the sewage for excreted compounds relevant to
      public health issues appears to have the potential to become a convenient source
      of real-time epidemiologic information.

PMID- 18709164
TI  - Protective effects of B vitamins and antioxidants on the risk of arsenic-related
      skin lesions in Bangladesh.
AB  - BACKGROUND: An estimated 25-40 million of the 127 million people of Bangladesh
      have been exposed to high levels of naturally occurring arsenic from drinking
      groundwater. The mitigating effects of diet on arsenic-related premalignant skin
      lesions are largely unknown. OBJECTIVES: The purpose of this study was to clarify
      the effects of the vitamin B group (thiamin, riboflavin, niacin, pyridoxine, and
      cobalamin) and antioxidants (vitamins A, C, and E) on arsenic-related skin
      lesions. METHODS: We performed a cross-sectional study using baseline data from
      the Health Effects of Arsenic Longitudinal Study (HEALS), 2000-2002, with
      individual-level, time-weighted measures of arsenic exposure from drinking water.
      A total of 14,828 individuals meeting a set of eligibility criteria were
      identified among 65,876 users of all 5,996 tube wells in the 25-km(2) area of
      Araihazar, Bangladesh; 11,746 were recruited into the study. This analysis is
      based on 10,628 subjects (90.5%) with nonmissing dietary data. Skin lesions were
      identified according to a structured clinical protocol during screening and
      confirmed with further clinical review. RESULTS: Riboflavin, pyridoxine, folic
      acid, and vitamins A, C, and E significantly modified risk of arsenic-related
      skin lesions. The deleterious effect of ingested arsenic, at a given exposure
      level, was significantly reduced (ranging from 46% reduction for pyridoxine to
      68% for vitamin C) for persons in the highest quintiles of vitamin intake.
      CONCLUSIONS: Intakes of B-vitamins and antioxidants, at doses greater than the
      current recommended daily amounts for the country, may reduce the risk of arsenic
      related skin lesions in Bangladesh.

PMID- 18709166
TI  - Error and bias in geocoding school and students' home addresses.

PMID- 18709165
TI  - Ambient ozone concentrations cause increased hospitalizations for asthma in
      children: an 18-year study in Southern California.
AB  - BACKGROUND: Asthma is the most important chronic disease of childhood. The U.S.
      Environmental Protection Agency has concluded that children with asthma continue
      to be susceptible to ozone-associated adverse effects on their disease.
      OBJECTIVES: This study was designed to evaluate time trends in associations
      between declining warm-season O(3) concentrations and hospitalization for asthma
      in children. METHODS: We undertook an ecologic study of hospital discharges for
      asthma during the high O(3) seasons in California's South Coast Air Basin (SoCAB)
      in children who ranged in age from birth to 19 years from 1983 to 2000. We used
      standard association and causal statistical analysis methods. Hospital discharge
      data were obtained from the State of California; air pollution data were obtained
      from the California Air Resources Board, and demographic data from the 1980,
      1990, and 2000 U.S. Census. SoCAB was divided into 195 spatial grids, and
      quarterly average O(3), sulfurdioxide, particulate matter with aerodynamic
      diameter < or = 10 microm, nitrogen dioxide, and carbon monoxide were assigned to
      each unit for 3-month periods along with demographic variables. RESULTS: O(3) was
      the only pollutant associated with increased hospital admissions over the study
      period. Inclusion of a variety of demographic and weather variables accounted for
      all of the non-O(3) temporal changes in hospitalizations. We found a time
      independent, constant effect of ambient levels of O(3) and quarterly hospital
      discharge rates for asthma. We estimate that the average effect of a 10-ppb mean
      increase in any given mean quarterly 1-hr maximum O(3) over the 18-year median of
      87.7 ppb was a 4.6% increase in the same quarterly outcome. CONCLUSIONS: Our data
      indicate that at current levels of O(3) experienced in Southern California, O(3)
      contributes to an increased risk of hospitalization for children with asthma.

PMID- 18709167
TI  - Road proximity increases risk of skeletal abnormalities in wood frogs from
      National Wildlife Refuges in Alaska.
AB  - BACKGROUND: Skeletal and eye abnormalities in amphibians are not well understood,
      and they appear to be increasing while global populations decline. Here, we
      present the first study of amphibian abnormalities in Alaska. OBJECTIVE: In this
      study we investigated the relationship between anthropogenic influences and the
      probability of skeletal and eye abnormalities in Alaskan wood frogs (Rana
      sylvatica). METHODS: From 2000 to 2006, we examined 9,269 metamorphic wood frogs
      from 86 breeding sites on five National Wildlife Refuges: Arctic, Innoko, Kenai,
      Tetlin, and Yukon Delta. Using road proximity as a proxy for human development,
      we tested relationships between skeletal and eye abnormalities and anthropogenic
      effects. We also examined a subsample of 458 frogs for the trematode parasite
      Ribeiroia ondatrae, a known cause of amphibian limb abnormalities. RESULTS:
      Prevalence of skeletal and eye abnormalities at Alaskan refuges ranged from 1.5%
      to 7.9% and were as high as 20% at individual breeding sites. Proximity to roads
      increased the risk of skeletal abnormalities (p = 0.004) but not eye
      abnormalities. The only significant predictor of eye abnormalities was year
      sampled (p = 0.006). R. ondatrae was not detected in any Alaskan wood frogs.
      CONCLUSIONS: Abnormality prevalence at road-accessible sites in the Kenai and
      Tetlin refuges is among the highest reported in the published literature.
      Proximity to roads is positively correlated with risk of skeletal abnormalities
      in Alaskan wood frogs.

PMID- 18709169
TI  - Children are likely to suffer most from our fossil fuel addiction.
AB  - BACKGROUND: The periods of fetal and child development arguably represent the
      stages of greatest vulnerability to the dual impacts of fossil fuel combustion:
      the multiple toxic effects of emitted pollutants (polycyclic aromatic
      hydrocarbons, particles, sulfur oxides, nitrogen oxides, metals) and the broad
      health impacts of global climate change attributable in large part to carbon
      dioxide released by fossil fuel burning. OBJECTIVES: In this commentary I
      highlight current scientific evidence indicating that the fetus and young child
      are at heightened risk of developmental impairment, asthma, and cancer from
      fossil fuel pollutants and from the predicted effects of climate disruption such
      as heat waves, flooding, infectious disease, malnutrition, and trauma. Increased
      risk during early development derives from the inherently greater biologic
      vulnerability of the developing fetus and child and from their long future
      lifetime, during which early insults can potentially manifest as adult as well as
      childhood disease. I cite recent reports concluding that reducing dependence on
      fossil fuel and promoting clean and sustainable energy is economically feasible.
      DISCUSSION: Although much has been written separately about the toxicity of
      fossil fuel burning emissions and the effects of climate change on health, these
      two faces of the problem have not been viewed together with a focus on the
      developing fetus and child. Adolescence and old age are also periods of
      vulnerability, but the potential for both immediate and long-term adverse effects
      is greatest when exposure occurs prenatally or in the early years. CONCLUSIONS:
      Consideration of the full spectrum of health risks to children from fossil fuel
      combustion underscores the urgent need for environmental and energy policies to
      reduce fossil fuel dependence and maximize the health benefits to this
      susceptible population. We do not have to leave our children a double legacy of
      ill health and ecologic disaster.

PMID- 18709173
TI  - The sprawl of food deserts.

PMID- 18709170
TI  - Relation between cord blood mercury levels and early child development in a World
      Trade Center cohort.
AB  - OBJECTIVE: This study was designed to determine whether prenatal mercury
      exposure, including potential releases from the World Trade Center (WTC)
      disaster, adversely affects fetal growth and child development. METHODS: We
      determined maternal and umbilical cord blood total mercury of nonsmoking women
      who delivered at term in lower Manhattan after 11 September 2001, and measured
      birth outcomes and child development. RESULTS: Levels of total mercury in cord
      and maternal blood were not significantly higher for women who resided or worked
      within 1 or 2 miles of the WTC in the month after 11 September, compared with
      women who lived and worked farther away. Average cord mercury levels were more
      than twice maternal levels, and both were elevated in women who reported eating
      fish/seafood during pregnancy. Regression analyses showed no significant
      association between (ln) cord or maternal blood total mercury and birth outcomes.
      Log cord mercury was inversely associated with the Bayley Scales of Infant
      Development psychomotor score [Psychomotor Development Index (PDI)] at 36 months
      (b = -4.2, p = 0.007) and with Performance (b = -3.4, p = 0.023), Verbal (b = 
      2.9, p = 0.023), and Full IQ scores (b = -3.8, p = 0.002) on the Wechsler
      Preschool and Primary Scale of Intelligence, Revised (WPPSI-R), at 48 months,
      after controlling for fish/seafood consumption and other confounders.
      Fish/seafood consumption during pregnancy was significantly associated with a 5.6
      to 9.9-point increase in 36-month PDI, and 48-month Verbal and Full IQ scores.
      CONCLUSIONS: Blood mercury was not significantly raised in women living or
      working close to the WTC site in the weeks after 11 September 2001. Higher cord
      blood mercury was associated with reductions in developmental scores at 36 and 48
      months, after adjusting for the positive effects of fish/seafood consumption
      during pregnancy.

PMID- 18709175
TI  - Community- and individual-level socioeconomic status and breast cancer risk:
      multilevel modeling on Cape Cod, Massachusetts.
AB  - BACKGROUND: Previous research demonstrated increased risk of breast cancer
      associated with higher socioeconomic status (SES) measured at both the individual
      and community levels. However, little attention has been paid to simultaneously
      examining both measures. OBJECTIVES: We evaluated the independent influences of
      individual and community SES on the risk of breast cancer using case-control
      data. Because our previous work suggests that associations may be stronger after
      including a latency period, we also assessed the effect of community-level SES
      assuming a 10-year latency period. METHODS: We obtained individual education for
      cases and matched controls diagnosed between 1987 and 1993 on Cape Cod,
      Massachusetts (USA). We acquired community-level SES from census data for 1980
      and 1990. Using SES data at diagnosis and 10 years earlier, we constructed models
      for breast cancer risk using individual-level SES only, community-level SES only,
      and a multilevel analysis including both. We adjusted models for other individual
      level risk factors. RESULTS: Women with the highest education were at greater
      risk of developing breast cancer in both 1980 and 1990 [odds ratio (OR) = 1.17
      and 1.19, respectively]. Similarly, women living in the highest-SES communities
      in 1990 had greater risk (OR = 1.30). Results were stronger in the analyses
      considering a latency period (OR = 1.69). Adjusting for intragroup correlation
      had little effect on the analyses. CONCLUSIONS: Models including individual- or
      community-level measures of SES produced associations similar to those observed
      in previous research. Results for models including both measures are consistent
      with a contextual effect of SES on risk of breast cancer independent of
      individual SES.

PMID- 18709174
TI  - Design issues in small-area studies of environment and health.
AB  - BACKGROUND: Small-area studies are part of the tradition of spatial epidemiology,
      which is concerned with the analysis of geographic patterns of disease with
      respect to environmental, demographic, socioeconomic, and other factors. We focus
      on etiologic research, where the aim is to make inferences about spatially
      varying environmental factors influencing the risk of disease. METHODS AND
      RESULTS: We illustrate the approach through three exemplars: a) magnetic fields
      from overhead electric power lines and the occurrence of childhood leukemia,
      which illustrates the use of geographic information systems to focus on areas
      with high exposure prevalence; b) drinking-water disinfection by-products and
      reproductive outcomes, taking advantage of large between- to within-area
      variability in exposures from the water supply; and c) chronic exposure to air
      pollutants and cardiorespiratory health, where issues of socioeconomic
      confounding are particularly important. DISCUSSION: The small-area epidemiologic
      approach assigns exposure estimates to individuals based on location of residence
      or other geographic variables such as workplace or school. In this way, large
      populations can be studied, increasing the ability to investigate rare exposures
      or rare diseases. The approach is most effective when there is well-defined
      exposure variation across geographic units, limited within-area variation, and
      good control for potential confounding across areas. CONCLUSIONS: In conjunction
      with traditional individual-based approaches, small-area studies offer a valuable
      addition to the armamentarium of the environmental epidemiologist. Modeling of
      exposure patterns coupled with collection of individual-level data on subsamples
      of the population should lead to improved risk estimates (i.e., less potential
      for bias) and help strengthen etiologic inference.

PMID- 18709178
TI  - A boundary integral approach to analyze the viscous scattering of a pressure wave
      by a rigid body.
AB  - The paper provides boundary integral equations for solving the problem of viscous
      scattering of a pressure wave by a rigid body. By using this mathematical tool
      uniqueness and existence theorems are proved. Since the boundary conditions are
      written in terms of velocities, vector boundary integral equations are obtained
      for solving the problem. The paper introduces single-layer viscous potentials and
      also a stress tensor. Correspondingly, a viscous double-layer potential is
      defined. The properties of all these potentials are investigated.By representing
      the scattered field as a combination of a single-layer viscous potential and a
      double-layer viscous potential the problem is reduced to the solution of a
      singular vectorial integral equation of Fredholm type of the second kind.In the
      case where the stress vector on the boundary is the main quantity of interest the
      corresponding boundary singular integral equation is proved to have a unique
      solution.

PMID- 18709177
TI  - In silico modeling of interstitial lung mechanics: implications for disease
      development and repair.
AB  - In this perspective, we first review some of the published literature on
      structural modeling of the mechanical properties of the lung parenchyma. Based on
      a recent study, we demonstrate why mechanical dysfunction accompanying
      parenchymal diseases such as pulmonary fibrosis and emphysema can follow a very
      different course from the progression of the underlying microscopic
      pathophysiology itself, particularly in the early stages. The key idea is related
      to the concept of percolation on elastic networks where the bulk modulus of the
      network suddenly changes when the fibrotic stiff regions or the emphysematous
      holes become suddenly connected across the network. We also introduce the concept
      of depercolation as a basis for the rational optimization of tissue repair.
      Specifically, we use these network models to predict the functional improvements
      that a hypothetical biological or tissue engineering repair could achieve. We
      find that rational targeted repair can have significant benefits over generic
      random repair. This concept may find application in the treatment of lung
      fibrosis, surgical, bronchoscopic, or biological lung volume reduction, or any
      future alveolar regeneration or tissue engineering solution to the repair of
      connective tissue damage of the lung.

PMID- 18709179
TI  - Mechanisms of sepsis and insights from clinical trials.
AB  - Multiple clinical trials of adjunctive therapy for sepsis and septic shock have
      been conducted to neutralize bacterial components or to modulate host
      inflammatory responses to infection but with limited success. Many therapies are
      only beneficial only in patients with a high severity of illness and have minimal
      or harmful effects in patients that are less severely ill. Improved measures of
      severity of illness and discovery of biomarkers to help identify these high-risk
      patients are needed.

PMID- 18709180
TI  - A Run-to-Run Control Strategy to Adjust Basal Insulin Infusion Rates in Type 1
      Diabetes.
AB  - Maintaining good glycemic control is a daily challenge for people with type 1
      diabetes. Insulin requirements are changing constantly due to many factors, such
      as levels of stress and physical activity. The basal insulin requirement also has
      a circadian rhythm, adding another level of complexity. Automating the adjustment
      of insulin dosing would result in improved glycemic control, as well as an
      improved quality of life by significantly reducing the burden on the patient.
      Building on our previous success of using run-to-run control for prandial insulin
      dosing (a strategy adapted from the chemical process industry), we show how this
      same framework can be used to adjust basal infusion profiles. We present a
      mathematical model of insulin-glucose dynamics which we augment in order to
      capture the circadian variation in insulin requirements. Using this model, we
      show that the run-to-run framework can also be successfully applied to adjust
      basal insulin dosing.

PMID- 18709181
TI  - HIV-Related Lung Disorders.
AB  - Highly active antiretroviral therapy (HAART) has dramatically altered the
      spectrum of morbidity and mortality in HIV-infected patients. This has been
      attributed to improvements in the lung microenvironment leading to enhanced
      pulmonary immunity, either by preventing the progressive loss of immune function
      or by actually promoting immune restoration. However, these changes have been
      accompanied by the recognition of new pulmonary complications in HIV-infected
      subjects, especially those associated with immune reconstitution. In this review
      we will describe how HIV infection alters the normal pulmonary environment,
      highlight the effect of HAART on these perturbations, and discuss potential
      complications of HAART in the lung, focusing on the pulmonary immune
      reconstitution inflammatory syndrome.

PMID- 18709182
TI  - The Application of Vinylogous Iminium Salt Derivatives and Microwave Accelerated
      Vilsmeier-Haack Reactions to Efficient Relay Syntheses of the Polycitone and
      Storniamide Natural Products.
AB  - Studies directed at the synthesis of polycitone and storniamide natural products
      via vinylogous iminium salts and microwave accelerated Vilsmeier-Haack
      formylations are described. The successful strategy relies on the formation of a
      2,4-disubstituted pyrrole or a 2,3,4-trisubstituted pyrrole from a vinamidinium
      salt or vinamidinium salt derivative followed by formylation at the 5-position of
      the pyrrole. Subsequent transformations of the selectively formylated pyrroles
      lead to efficient and regiocontrolled relay syntheses of the respective pyrrole
      containing natural products.

PMID- 18709184
TI  - Editorial - analytical science in China.

PMID- 18709183
TI  - Generalized Self-Consistency: Multinomial logit model and Poisson likelihood.
AB  - A generalized self-consistency approach to maximum likelihood estimation (MLE)
      and model building was developed in (Tsodikov, 2003) and applied to a survival
      analysis problem. We extend the framework to obtain second-order results such as
      information matrix and properties of the variance. Multinomial model motivates
      the paper and is used throughout as an example. Computational challenges with the
      multinomial likelihood motivated Baker (1994) to develop the Multinomial-Poisson
      (MP) transformation for a large variety of regression models with multinomial
      likelihood kernel. Multinomial regression is transformed into a Poisson
      regression at the cost of augmenting model parameters and restricting the problem
      to discrete covariates. Imposing normalization restrictions by means of Lagrange
      multipliers (Lang, 1996) justifies the approach. Using the self-consistency
      framework we develop an alternative solution to multinomial model fitting that
      does not require augmenting parameters while allowing for a Poisson likelihood
      and arbitrary covariate structures. Normalization restrictions are imposed by
      averaging over artificial "missing data" (fake mixture). Lack of probabilistic
      interpretation at the "complete-data" level makes the use of the generalized self
      consistency machinery essential.

PMID- 18709185
TI  - Development of phosphopeptide enrichment techniques for phosphoproteome analysis.
AB  - Protein phosphorylation is one of the most biologically relevant and ubiquitous
      post-translational modifications. The analysis of protein phosphorylation is very
      challenging due to its highly dynamic nature and low stoichiometry. In this
      article, recent techniques developed for phosphoproteome analysis are reviewed
      with an emphasis on the new developments in this field in China. To improve the
      performance of phosphoproteome analysis, many novel methods, either by
      application of new separation mechanisms or by adoption of new separation
      materials, were developed to specifically enrich phosphopeptides from complex
      protein digests. A series of new materials, including nanostructure materials,
      magnetic materials, and monolithic materials, were applied to prepare immobilized
      affinity chromatography or metal oxide affinity chromatography to improve the
      performance of phosphopeptide enrichment. Besides, new software tools were also
      developed to validate phosphopeptide identification and predict kinase specific
      phosphorylation sites.

PMID- 18709186
TI  - Review on the theory of moving reaction boundary, electromigration reaction
      methods and applications in isoelectric focusing and sample pre-concentration.
AB  - Since 1970, a series of systematic investigations have been performed on three
      modes of moving reaction boundaries (MRBs), viz. moving precipitate boundary
      (MPB), moving neutralization boundary (MNB) and moving chelation boundary (MCB).
      So far, there has not been any review on them. Herein, we firstly review the MPB
      with respect to its velocity, product concentration, elution displacement,
      stacking effect, separation effect, judgment expressions and related procedures.
      We then make a review on the MNB about its theory, demonstration, improvement,
      and uses in isoelectric focusing (IEF), sample stacking, MNB-based stacking
      mechanisms and relevant computer simulations. We further give a review on the MCB
      regarding the relevant theory, verifications, and applications in EDTA-based
      sweeping and computer simulation. Finally, we give an outlook on the MRB study.
      More than 150 references are cited.

PMID- 18709187
TI  - A new method for the study of G-quadruplex ligands.
AB  - A new method for the study of G-quadruplex ligands was developed, in which the
      interaction of G-quadruplexes with ligands can be judged by the naked eye,
      eliminating the need for any expensive machines.

PMID- 18709188
TI  - Dopamine detection based on its quenching effect on the anodic
      electrochemiluminescence of CdSe quantum dots.
AB  - Anodic electrochemiluminescence (ECL) of CdSe quantum dots (QDs) in a neutral
      system was for the first time observed at a relatively low potential by using
      sulfite as a co-reactant to produce the ECL emission at an indium tin oxide (ITO)
      electrode, which could be used for the sensitive detection of ECL quenchers using
      dopamine (DA) as a model molecule.

PMID- 18709189
TI  - Chemiluminescent detection of DNA hybridization and single-nucleotide
      polymorphisms on a solid surface using target-primed rolling circle
      amplification.
AB  - A new chemiluminescent (CL) method has been developed for the sensitive detection
      of DNA hybridization and single-nucleotide polymorphisms (SNPs) with target
      primed rolling circle amplification (RCA). The capture oligonucleotide probe is
      firstly immobilized on a polystyrene well plate and then hybridized with the wild
      DNA target. A designed padlock probe is circularized after perfect hybridization
      to the DNA target. Then the RCA reaction can be initiated from the DNA target
      that acts as a primer and generates a long tandem single-strand of DNA with
      repeat sequences. In contrast, the mutant DNA target, which contains a mismatched
      base with the padlock probe, cannot initiate the RCA reaction and primes only a
      limited extension with the unligated padlock probe. Afterwards, a biotinylated
      oligonucleotide is used to hybridize with the RCA product in each repeat sequence
      and streptavidin-alkaline phosphatase (STV-AP) is employed to combine the
      anchored biotin. The DNA target is detected with the CL reaction of STV-AP and 3
      (2'-spiroadamantane)-4-methoxy-4-(3''-phosphoryloxy)phenyl-1,2-dioxetane (AMPPD).
      With the RCA-based method, the sensitivity of DNA detection can be increased by
      about two orders of magnitude compared with that of direct DNA hybridization. A
      DNA target as low as 3.6 pM can be detected. Wild-type DNA and the one-base
      mutant DNA can be differentiated with high selectivity through this RCA reaction.

PMID- 18709190
TI  - Determination of arsenate by sorption pre-concentration on polystyrene beads
      packed in a microfluidic device with chemiluminescence detection.
AB  - A highly sensitive chemiluminescence (CL) method for the determination of
      arsenate in water based on a simple microfluidic device was developed. The method
      was based on sorption pre-concentration of arsenate as a form of
      vanadomolybdoarsenate heteropoly acid (VMoAs-HPA) ion-paired with
      hexadecyltrimethylammonium bromide on the surface of polystyrene beads packed in
      a microfluidic device monitored by chemiluminescence detection. The composition
      of the VMoAs-HPA complex was studied by varying the concentrations of ammonium
      molybdate, ammonium vanadate and sulfuric acid with a variable-size simplex
      optimization process, of which the optimum concentrations were 6.3 x 10(-5), 5.0
      x 10(-6) and 1.0 x 10(-2) M, respectively. In this work, 1.0 x 10(-3) M
      ethylenediaminetetraacetic acid was added to all work solutions to remove the
      interferences of the other metal ions on the CL detection. The integration of
      sorption pre-concentration not only increased the detection sensitivity but also
      eliminated the interference from phosphate and chromate. The calibration plot was
      linear from 1.0 x 10(-7) to 5.0 x 10(-5) M As(v). The limit of detection was 8.9
      x 10(-8) M As(v) (S/N = 3). The time required for one analysis run was as short
      as 5 min. The relative standard deviation was 5.9% (n = 9). This method was
      successfully applied to the determination of arsenate in mineral-, drinking- and
      tap-water samples.

PMID- 18709191
TI  - A novel assembly of Au NPs-beta-CDs-FL for the fluorescent probing of cholesterol
      and its application in blood serum.
AB  - A novel assembly of Au NPs-beta-CDs-FL for the fluorescent probing of cholesterol
      (Cho) is provided. Gold nanoparticles (Au NPs) possessing a high extinction
      coefficient function can be used as excellent fluorescent quenchers in Au NP
      fluorophore composites. Inclusion of fluorescein (FL) into beta-cyclodextrin
      (beta-CD) makes fluorescence resonance energy transfer (FRET) occur through the
      donor and quencher nearby. FRET switches off because of the cholesterol-induced
      release of FL from beta-CD cavity, which results in the fluorescence recovery of
      the quenched dye. Spectral analysis supported the idea that the signal
      enhancement was attributed to the formation of an inclusion complex of the
      cholesterol moiety in beta-CD, resulting in separation of FL from the Au NPs.
      This phenomenon is explained by the guest-induced location change of the FL from
      inside to outside the cavity, suggesting that the assembly of Au NPs-beta-CDs-FL
      is effective as a fluorescent probe for cholesterol recognition. The fluorescence
      increase is proportional to the concentration of cholesterol in the range of
      approx. 30 nM to 15 muM. A concentration of cholesterol as low as 9 nM would be
      readily detected. The precision of the method applied to the determination of
      quantities of cholesterol present in human blood serum were satisfactory.

PMID- 18709192
TI  - An electrochemical sensor for pesticide assays based on carbon nanotube-enhanced
      acetycholinesterase activity.
AB  - There has been urgent demand for rapid, sensitive and cost-effective pesticide
      assay technologies due to the global attention of environmental and food-safety
      problems. Acetycholinesterase (AChE)-based electrochemical sensors have attracted
      significant interest toward this goal. In this contribution, we introduced
      multiwalled carbon nanotubes (MWNTs) into our sensor design, where they played
      dual enhancement roles; first is that MWNTs loaded on glassy carbon (GC)
      electrodes significantly increase surface areas, facilitating the electrochemical
      polymerization of prussian blue (PB), a redox mediator for the electrochemical
      oxidation of the enzymatic product, thiocholine (TCh). Second, MWNTs enhance the
      enzymatic activity of AChE, as manifested by the decreased Michaelis-Menten
      constant (K(m)). As a result of these two important enhancement factors offered
      by MWNTs, our electrochemical pesticide sensor exhibited rapid response and high
      sensitivity toward the detection of a series of pesticides. Moreover, we
      demonstrated that this sensor was stable, reproducible and selective enough for
      detection in real samples.

PMID- 18709194
TI  - Covalent immobilization of carbohydrates on sol-gel-coated microplates.
AB  - Carbohydrate microarrays have attracted increasing attention in recent years
      because of their ability to monitor biologically important protein-carbohydrate
      interactions in a high-throughput manner. Here we have developed an effective
      approach to immobilizing intact carbohydrates directly on polystyrene microtiter
      plates coated with amine-functionalized sol-gel monolayers. Lectin binding was
      monitored by fluorescence spectroscopy using these covalent arrays of
      carbohydrates that contained six mono- and di-saccharides on the microplates. In
      addition, binding affinities of lectin to carbohydrates were also quantitatively
      analyzed by determining IC(50) values of lectin-specific antibody with these
      arrays. Our results indicate that microplate-based carbohydrate arrays can be
      efficiently fabricated by covalent immobilization of intact carbohydrates on sol
      gel-coated microplates. The microplate-based carbohydrate arrays can be applied
      for screening of protein-carbohydrate interactions in a high-throughput manner.

PMID- 18709193
TI  - Determination of diuretics in human urine by hollow fiber-based liquid-liquid
      liquid microextraction coupled to high performance liquid chromatography.
AB  - In competition sports, a diuretic is a substance widely prohibited by the World
      Anti-Doping Agency (WADA). In this paper, a sensitive, rapid and convenient
      analytical method for the determination of acidic [furosemide (FUROS) and
      bumetanide (BUMET)] and basic [triamterene (TRIAM)] diuretics in human urine was
      developed by hollow fiber-based liquid-liquid-liquid microextraction (LLLME)
      coupled with HPLC-UV. The LLLME conditions, such as the organic extraction
      solvent, the acidity and basicity of the donor- and acceptor-phases, stirring
      speed, extraction time and ionic strength, were studied in detail. Under the
      optimum conditions, the linear ranges of furosemide, bumetanide and triamterene
      were 1.2-250, 5.0-250 and 5.0-500 ng mL(-1), respectively. The detection limits
      were 0.5 ng mL(-1) for furosemide, 1.2 ng mL(-1) for bumetanide and 2.0 ng mL(-1)
      for triamterene. The LLLME obtained a great improvement of the detection limits
      for all the analytes considered here, to the ng mL(-1) level, which almost
      reaches the level of the LC-MS method. This new LLLME method provided very high
      enrichments: 117-fold for furosemide, 175-fold for bumetanide and 68-fold for
      triamterene. Since the hollow fiber membrane was sealed, it could be used for
      extracting the diuretics directly from 'dirty' human urine samples without any
      clean-up procedures. With LLLME-HPLC, the corresponding recoveries ranged from
      79.2 to 109% with the RSDs not exceeding 5.5% for the three diuretics in the
      spiked urine samples. The method was successfully applied to analyse the amounts
      of the three diuretics in real urine samples of volunteers after oral drug
      taking. This new method proves to be sensitive and reliable and thus renders a
      very suitable means for the determination of trace diuretics in human urine based
      on the common HPLC instrument.

PMID- 18709195
TI  - Interactions between protein and porphyrin-containing cyclodextrin supramolecular
      system: a fluorescent sensing approach for albumin.
AB  - The interactions of meso-tetraphenylporphyrin (TPP), meso-tetraphenylporphyrin
      cobalt(ii) (CoTPP) and protein in the presence of a cyclodextrin derivative,
      heptakis(2,6-di-O-n-octyl)-beta-cyclodextrin (Oc-beta-CD), have been
      investigated. In the presence of Oc-beta-CD, significant increase of TPP
      fluorescence was realized, but the increased fluorescence was quenched by CoTPP.
      To further investigate the fluorescence-quenched system and explore its potential
      application in bioanalysis, a strategy has been devised to restore the quenching
      fluorescence of TPP upon interacting with protein. The restoration of TPP
      fluorescence in the present system is fast and accomplished upon interaction with
      bovine serum albumin (BSA) or human serum albumin (HSA). On the basis of the
      spectroscopic measurement and excited state fluorescence lifetime, the mechanism
      of TPP fluorescence quenching is attributed to formation of a ground-state
      complex of TPP and CoTPP, and the fluorescence restoration is attributed to the
      binding of CoTPP with the protein molecule which destroys the aggregate,
      releasing the free base porphyrin. With optimized conditions, the calibration
      equations are linear from 0.80 to 75.4 microg mL(-1) BSA and from 3.20 to 93.2
      microg mL(-1) HSA. The corresponding detection limits are 0.32 microg mL(-1) for
      BSA and 1.06 microg mL(-1) for HSA, respectively. The method was used for the
      direct assay of HSA content in human serum. The result is comparable to that
      obtained by another method. The recovery from BSA in synthetic sample is also
      satisfactory.

PMID- 18709196
TI  - Nanoscale-enhanced Ru(bpy)3(2+) electrochemiluminescence labels and related
      aptamer-based biosensing system.
AB  - A unique multilabeling at a single-site protocol of the Ru(bpy)(3)(2+)
      electrochemiluminescence (ECL) system is proposed. Nanoparticles (NPs) were used
      as assembly substrates to enrich ECL co-reactants of Ru(bpy)(3)(2+) to construct
      nanoscale-enhanced ECL labels. Two different kinds of NP substrates [including
      semiconductor NPs (CdTe) and noble metal NPs (gold)] capped with 2
      (dimethylamino)ethanethiol (DMAET) [a tertiary amine derivative which is believed
      to be one of the most efficient of co-reactants of the Ru(bpy)(3)(2+) system]
      were synthesized through a simple one-pot synthesis method in aqueous media.
      Although both CdTe and gold NPs realized the enrichment of ECL co-reactants, they
      presented entirely different ECL performances as nanoscale ECL co-reactants of
      Ru(bpy)(3)(2+). The different effects of these two NPs on the ECL of
      Ru(bpy)(3)(2+) were studied. DMAET-capped CdTe NPs showed enormous signal
      amplification of Ru(bpy)(3)(2+) ECL, whereas DMAET-capped gold NPs showed a
      slight quenching effect of the ECL signal. DMAET-capped CdTe NPs can be
      considered to be excellent nanoscale ECL labels of the Ru(bpy)(3)(2+) system, as
      even a NP solution sample of 10(-18) M was still detectable after an
      electrostatic self-assembly concentration process. DMAET-capped CdTe NPs were
      further applied in the construction of aptamer-based biosensing system for
      proteins and encouraging results were obtained.

PMID- 18709197
TI  - Integrated GC-MS and LC-MS plasma metabonomics analysis of ankylosing
      spondylitis.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that
      predominantly affects the axial skeleton in adolescent patients. The natural
      history of the disease remains poorly characterized. In this study, we combined
      GC-MS and LC-MS techniques to evaluate the major metabolic changes in the plasma
      of AS patients in view of metabonomics. Univariate and multivariate analysis were
      employed for altered metabolite comparison and pattern recognition. Application
      of supervised partial least-squares discrminant analysis to either GC-MS or LC-MS
      data allowed accurate discrimination of AS patients from normal controls,
      demonstrating its potential diagnostic utilization. In addition, AS patients
      presented elevated plasma concentrations of proline, glucose, phosphate, urea,
      glycerol, phenylalanine and homocysteine but reduced levels of phosphocholines,
      tryptophan and a bipeptide - phenylalanyl-phenylalanine. In the context of their
      involved metabolic pathways, the identified metabolites were discussed
      accordingly. This investigation primarily proved that integrated chromatography
      mass spectrometry and integrated uni- and multi-variate statistical analysis
      facilitated metabonomics to be a more promising tool in disease research.

PMID- 18709198
TI  - Investigation of the interactions between silver nanoparticles and Hela cells by
      scanning electrochemical microscopy.
AB  - The interactions between Hela cells and silver nanoparticles (AgNPs) have been
      studied by scanning electrochemical microscopy (SECM) with both IrCl(6)(2-/3-)
      and Fe(CN)(6)(3-/4-) as the dual mediators. IrCl(6)(2-), which can be produced in
      situ and react with AgNPs, is used as the mediator between the AgNPs on the cells
      and the SECM tip. Another redox couple, Fe(CN)(6)(3-/4-), which has a similar
      hydrophilicity to IrCl(6)(2-/3-), but cannot react with AgNPs, is also employed
      for the contrast experiments. The cell array is cultured successfully onto a
      Petri dish by microcontact printing (muCP) technique, which can provide a basic
      platform for studying of single cells. The approach curve and line scan are the
      two methods of SECM employed here to study the Hela cells. The former can provide
      the information about the interaction between Hela cells and AgNPs whereas the
      later gives the cell imaging. The permeability of cell membranes and morphology
      are two main factors which have effects on the feedback mode signals when
      K(3)Fe(CN)(6) is used as the mediator. The permeability of the cell membranes can
      be ignored after interaction with high concentration of AgNP solution and the
      height of the Hela cells is slightly decreased in this process. The kinetic rate
      constants (k(0)) between IrCl(6)(2-) and Ag on the Hela cell can be evaluated
      using K(3)IrCl(6) as the mediator, and they are increased with the higher
      concentrations of the AgNP solutions. The k(0) is changed about 10 times from
      0.43 +/- 0.04 x 10(-4) to 1.25 +/- 0.07 x 10(-4) and to 3.93 +/- 1.9 x 10(-4) cm
      s(-1) corresponding to 0, 1 and 5 mM of AgNO(3) solution. The experimental
      results demonstrate that the AgNPs can be adsorbed on the cell surface and
      detected by SECM. Thus, the amount of AgNPs adsorbed on cell membranes and the
      permeability or morphology changes can be investigated simultaneously using this
      approach. The dual mediator system and cell array fabricated by muCP technique
      can provide better reproducibility because they can simplify experiments, and
      provide a platform for further single cell detection.

PMID- 18709199
TI  - Carrier-resolved technology for homogeneous and multiplexed DNA assays in a 'one
      pot reaction'.
AB  - For clinical diagnosis, a small number of targets (2-10 biomarkers) are often all
      that is required for disease assessment and accurate early disease diagnosis. In
      the current paper we have developed novel, carrier-resolved, single-label-based
      multiplexed assays for the simultaneous detection and quantification of a limited
      number of DNA targets associated with breast cancer. In contrast to current
      encoding strategies, every hybridization signal for the corresponding DNA target
      in our protocol is uniquely immobilized onto one carrier vehicle with a unique
      and intrinsic physico-chemical signature. Moreover, a simple chemiluminescence
      setup is employed to read the carrier code instead of expensive and complicated
      flow-cytometer or imaging-systems commonly used for multiplexed assays. Herein we
      demonstrate a new protocol using three homogeneous carriers, i.e. thermo
      sensitive poly(N-isopropylacrylamide) (PNIP), polystyrene beads, and magnetic
      beads respectively. This new methodology allowed for the simultaneous
      determination of three oligonucleotide sequences (60 bases in length) associated
      with the breast cancer gene (BRCA1) and showed high selectivity and attomolar
      femtomolar sensitivity. The mixture of three different capture probe conjugates
      first hybridizes with three corresponding target sequences, sandwiches with three
      biotinylated DNAs, and then reacts with peroxidase-streptavidin polymer in a
      single vessel without any washing, leading to the development of a 'one-pot
      reaction system'. Only one washing step in our protocol is required prior to
      detection leading to our whole procedure being simple and efficient. The results
      show that the hybridization response to sample mixtures containing increasing
      levels of each target is proportional to the amount of corresponding DNA targets,
      indicating minimal cross-interferences. The work presented here validates the
      design and concept of a system for the detection of a limited number of DNA
      targets and provides the foundation for the development of highly sensitive
      techniques with increased multi-analyte capabilities.

PMID- 18709200
TI  - Microfluidic chip-based valveless flow injection analysis system with gravity
      driven flows.
AB  - In this work, a microfluidic chip-based valveless flow injection analysis (FIA)
      system with gravity-driven flows and liquid-core waveguide (LCW) spectrometric
      detection was developed. Automated sample injection in the 0.3-6.4 nL range under
      gated injection mode was achieved by controlling the vertical position of the
      waste reservoir fixed on a moving platform and the residence time of the
      reservoir in each position, without the requirement of microvalves or
      electrokinetic manipulation. An integrated LCW spectrometric detection system was
      built on the chip by coupling a 20 mm-long Teflon AF 2400 capillary with the
      microchannel to function as a LCW flow cell, using a green LED as light source
      and a photodiode as detector. The performance of the system was demonstrated in
      the determination of [NO(2)](2-) based on the Saltzman reaction. Linear
      absorbance response was obtained in the range of 0.1-20 mg L(-1) (R(2) = 0.9910),
      and a good reproducibility of 0.34% RSD (n = 17) was achieved.

PMID- 18709201
TI  - Self-assembled multilayer of gold nanoparticles for amplified electrochemical
      detection of cytochrome c.
AB  - Although different kinds of film materials and some modification techniques are
      applied for the development of protein-film electrochemistry, the design of a
      more ordered adsorption platform with improved sensitivity is still required.
      Here we employ single-strand DNA (ssDNA)-functionalized gold nanoparticles as
      scaffolds for the construction of a multilayered uniform self-assembled structure
      via the hybridization of complementary ssDNA. After adsorbing with native
      conformation onto the uniformly built electrode, cytochrome c responded very well
      in voltammetry experiments. The peak currents increase with the addition of the
      number of gold nanoparticle layers, which indicates that the multilayer gold
      nanoparticles not only provide a compatible microenvironment for the protein to
      undergo direct electron transfer reactions but also amplify the electrochemical
      signals by increasing the binding sites for the protein immobilization.
      Furthermore, ultra-sensitive detection of cytochrome c by using this multilayer
      gold nanoparticle-modified electrode is carried out. The linear range is from 2 x
      10(-9) to 1 x 10(-7) M with a detection limit of 6.7 x 10(-10) M.

PMID- 18709202
TI  - Label-free electrochemical differentiation of phosphorylated and non
      phosphorylated peptide by electro-catalyzed tyrosine oxidation.
AB  - Protein phosphorylation plays an important role in many significant cellular
      processes, and has thus gained tremendous interest in the field of proteomics.
      The electro-active tyrosine residue, as an important receptor of phosphorylation
      in proteins, exhibits electro-inactivity after being phosphorylated on the
      hydroxy group of its aromatic ring. In this study, the electrochemical oxidation
      of tyrosine on indium tin oxide (ITO) electrodes was catalyzed with an electron
      mediator Os(bpy)(3)(2+) (bpy = 2,2'-bipyridine) and was employed as a signal
      reporter to differentially detect non-phosphorylated and phosphorylated peptides.
      A short, tyrosine-containing peptide glu-glu-glu-glu-glu-tyr (EY-6) was
      immobilized on an ITO surface using the layer-by-layer self-assembly method, and
      was detected by cyclic voltammetry in an Os(bpy)(3)(2+) solution. The limit of
      detection was about 0.23 microg mL(-1) EY-6 in solution. The phosphorylated
      peptide glu-glu-glu-glu-glu-tyr-OP (EY-6P) did not produce an appreciable
      oxidation current on the electrode. Surface plasmon resonance measurements
      revealed that the amount of EY-6 and EY-6P adsorbed on the sensor chip surface
      was 269 and 378 pg mm(-2), respectively. The poly(glu, tyr) (4 : 1) peptide, a
      protein tyrosine kinase substrate, was also detected by the same approach, with a
      detection limit of 0.65 microg mL(-1). This new approach offers the possibility
      of label-free and on-chip detection of protein tyrosine kinase activity.

PMID- 18709203
TI  - Gold nanoparticle-based immunoassay by using non-stripping chemiluminescence
      detection.
AB  - A novel microplate-compatible chemiluminescence (CL) immunoassay has been
      developed for the determination of human immunoglobulin G (IgG) based on the
      luminol-AgNO(3)-gold nanoparticles CL system. Polystyrene microtiter plates were
      used for both immunoreactions and CL measurements. The primary antibody, goat
      anti-human IgG, was first immobilized on polystyrene microwells. Then the antigen
      (human IgG) and the gold-labeled second antibody were connected to the microwells
      successively to form a sandwich-type immunocomplex. The gold label could trigger
      the reaction between luminol and AgNO(3), accompanied by light emission. Under
      the optimized conditions, the CL intensity of the system was linear with the
      logarithm of the concentration of human IgG in the range from 25 to 5000 ng mL(
      1), with a detection limit of 12.8 ng mL(-1) ( approximately 80 pM) at a signal
      to noise ratio of three (S/N = 3). Compared with other reported CL immunoassay
      method based on gold labels, the proposed CL protocol avoids a strict stripping
      procedure or difficult to control synthesis processes, making the method more
      simple, time-saving and easily automated. The present CL method is promising for
      the determination of clinically important bioactive analytes.

PMID- 18709204
TI  - Aptamer-based electrochemical sensors that are not based on the target binding
      induced conformational change of aptamers.
AB  - This study describes a new kind of aptamer-based electrochemical sensor that is
      not based on the target binding-induced conformational change of the aptamers by
      using a 15-mer thrombin-binding aptamer (5'-GGTTGGTGTGGTTGG-3') as the model
      oligonucleotide. The sensors are developed by first self-assembling the aptamer
      (i.e. a thrombin-binding aptamer) onto an Au electrode and then hybridizing the
      assembled aptamer with a ferrocene (Fc)-labeled short aptamer-complementary DNA
      oligonucleotide to form an electroactive double-stranded DNA (ds-DNA)
      oligonucleotide onto the Au electrode. The binding of the target (i.e. thrombin)
      towards the aptamer essentially destroys the Watson-Crick helix structure of the
      ds-DNA oligonucleotide assembled onto the electrode and leads to the dissociation
      of the Fc-labeled short complementary DNA oligonucleotide from the electrode
      surface to the solution, resulting in a decrease in the current signal obtained
      at the electrode, which can be used for the determination of the target. With the
      thrombin-binding aptamer as the model oligonucleotide, the current decrease
      obtained with the aptamer-based electrochemical sensors is linear with the
      concentration of thrombin within the concentration range from 0 to 10 nM
      (DeltaI/nA = 6.7C(thrombin)/nM + 2.8, gamma = 0.975). Unlike most kinds of
      existing aptamer-based electrochemical sensor, the electrochemical aptasensors
      demonstrated here are not based on the conformational change of the aptamers
      induced by the specific target binding. Moreover, the aptasensors are essentially
      label-free and are very responsive toward the targets. This study may pave a
      facile and general way to the development of aptamer-based electrochemical
      sensors.

PMID- 18709205
TI  - Integrated strong cation exchange/capillary reversed-phase liquid
      chromatography/on-target digestion coupled with mass spectrometry for
      identification of intact human liver tissue proteins.
AB  - We present a comprehensive method for proteome analysis that integrates both
      intact protein separation and proteolytic fragment characterization mass
      spectrometric approaches. Strong cation exchange chromatography (SCX) was used as
      the first separation dimension and capillary reversed-phase liquid chromatography
      (cRPLC) was integrated as the second separation dimension. Fractions from SCX
      were collected offline and loaded onto cRPLC. Effluents from cRPLC were directly
      deposited onto the MALDI target plates and further digested by using a rapid on
      probe tryptic digestion technique. This approach minimizes the amount of time and
      extensive labor required for traditional in-solution digestion followed by
      exhaustive sample cleanup and transfer. MALDI-TOF/TOF was used for subsequent
      analyses. The sensitivity of on-target digestion is showed by analyzing 0.07 ng
      of myoglobin, 0.07 ng of cytochrome c and 0.7 ng BSA. The high efficiency of the
      overall system was demonstrated by the analysis of intact proteins extracted from
      normal human liver tissue. In total, 458 proteins were identified, which proved
      the system's promising potential for analysis and application in proteomics.

PMID- 18709206
TI  - Surface plasmon resonance imaging of limited glycoprotein samples.
AB  - A surface plasmon resonance imaging method has been developed for high throughput
      recognition and determination of low level glycoproteins with limited sample
      volume at least down to 50 nL. Chicken ovalbumin and immunoglobulin G were chosen
      as model compounds while bovine serum albumin and lysozyme were used as control.
      Each protein, at a concentration of 0.0080-1.0 mg mL(-1), was printed on one gold
      sensing film, and the films were simultaneously reacted with a probe solution and
      viewed using a laboratory-built surface plasmon resonance imaging system. The
      imaging signals were dependent on the concentration and the type of analyte, with
      a limit of detection down to at least 0.5 ng. The glycoproteins dotted at either
      1.0 mg mL(-1) or 0.010 mg mL(-1) were easily differentiated from the non
      glycoproteins by reaction with 200 nM concanavalin A (con A), giving a limit of
      recognition down also to 0.5 ng glycoprotein. This imaging method was hence
      considered a new tool for analyzing glycoproteins.

PMID- 18709207
TI  - Recognition of single-base mismatch DNA by Au nanoparticle-assisted
      electroelution.
AB  - A simple, convenient and effective method based on the surface plasmon resonance
      (SPR) technique was introduced for recognition of single-base mismatch DNA
      (smDNA) by Au nanoparticle (AuNPs)-assisted electroelution. In this method,
      target DNA, including perfectly matched DNA and smDNA, hybridized with the DNA
      probes immobilized on Au film and AuNPs, then the Au film was negatively charged.
      Owing to the difference in stability between single-base mismatch and perfect
      match DNA, effective distinction between complementary DNA (cDNA) and smDNA was
      achieved in the presence of an electric field: double-stranded DNA (dsDNA) formed
      between smDNA targets and DNA probes was denatured by the repulsion force acting
      on the negatively-charged DNA-linked AuNPs, while the perfectly matched duplex
      was not influenced. However, if the AuNPs were absent, the effects of cDNA and
      smDNA were not distinguishable. The effects of electric field intensity and
      mismatch sites were also investigated. All of the operations were performed under
      mild conditions. The results showed that AuNP-assisted electroelution may be
      exploited for the construction of biosensors with high selectivity.

PMID- 18709208
TI  - The Farmer Life School: experience from an innovative approach to HIV education
      among farmers in South Africa.
AB  - The Farmer Life School (FLS) is an innovative approach to integrating HIV
      education into life skills and technical training for farmers. This study aims to
      gain insight into the strengths and weaknesses of this relatively new approach,
      through the implementation of an adapted version in South Africa. The results are
      presented of a pilot with three groups of community gardeners, predominantly
      women, attending weekly sessions. Impact was assessed in terms of three key
      elements: participation, learning, and empowerment. Data were collected through
      extensive session reports, follow-up interviews, and reflection exercises with
      facilitators and participating groups and individuals. The results suggest that a
      group-based discovery learning approach such as the FLS has great potential to
      improve food security and wellbeing, while allowing participants to explore
      issues around HIV/AIDS. However, the analysis also shows that HIV/AIDS-related
      illness and death, and the factors that drive the epidemic and its impact,
      undermine farmers' ability to participate, the safety and trust required for
      learning, and the empowerment process. Participatory approaches such as the FLS
      require a thorough understanding of and adaptation to the context.

PMID- 18709209
TI  - Establishing support groups for HIV-infected women: using experiences to develop
      guiding principles for project implementation.
AB  - HIV-infected women need support to deal with their diagnosis as well as with the
      stigma attached to HIV. As part of their practical training, Master's-level
      psychology students negotiated with the staff of four clinics in townships in
      Tshwane, South Africa, to establish support groups for HIV+ women and offered to
      assist them in facilitating the groups. This study aimed to understand why the
      implementation of groups was successful in one clinic and not other clinics. The
      student reports on their experiences and interaction with clinic staff and
      clients were used as sources of data. Using qualitative data analysis, different
      dynamics and factors that could affect project implementation were identified in
      each clinic. The socio-ecological and systems theories were used to understand
      implementation processes and obstacles in implementation. The metaphor of
      building a bridge over a gorge was used to describe the different phases in and
      obstacles to the implementation of the intervention. Valuable lessons were
      learnt, resulting in the development of guiding principles for the implementation
      of support groups in community settings.

PMID- 18709210
TI  - The political context of AIDS-related stigma and knowledge in a South African
      township community.
AB  - The purpose of this study was to examine the presentation of AIDS-related stigma
      and knowledge within the political context of the South African government's
      response to the AIDS epidemic. It was during the 2000 - 2004 period that key
      government officials publicly challenged the orthodox views of HIV/AIDS, with the
      South African president, Thabo Mbeki, actively positing the primary role of
      poverty and other socio-economic stressors in the progression of the AIDS
      epidemic. This discursive position had real-time effects for AIDS policy-making
      and ultimately delayed the implementation of a national antiretroviral (ARV)
      rollout programme. Consequently this position was criticised by commentators in
      the media and elsewhere for contributing to an already widespread climate of AIDS
      stigmatization and misinformation. To shed more light on these claims we
      conducted a survey in 2005 in Atteridgeville, a South African township, and
      compared results with those of a similar survey conducted shortly after ARV
      medications became available in 2004. Results indicated a reduction in AIDS
      stigma levels across the 1-year period, and that those participants who endorsed
      contentious political views (such as those expressed by key government officials)
      were more likely to have a higher level of AIDS-related stigma than those who
      disagreed. Nevertheless, this study cautions against drawing a causal
      relationship between the South African government's position and IDS-stigmatizing
      attitudes, and suggests that further political and social factors be accounted
      for in an attempt to gain a fuller understanding of this seemingly complex
      relationship.

PMID- 18709211
TI  - Condom use as part of the wider HIV prevention strategy: experiences from
      communities in the North West Province, South Africa.
AB  - Correct and consistent condom usage remains a pivotal strategy in reaching the
      target set by the South African government to reduce new HIV infections by 50% in
      the next 5 years. Studies have found that there has been an increase in condom
      usage by some categories of the population, but usage has not yet reached the
      desired levels in order to meet the target. This article reports on the findings
      of a study on condom usage in eight communities in the North West Province, which
      was part of a wider HIV and AIDS programme evaluation commissioned by the North
      West Provincial Department of Health. The main aim was to assess accessibility to
      condoms, and knowledge, attitudes and practices around condom use by four sampled
      communities in the North West Province. Eight focus group discussions were held
      and 50 households were interviewed. The study found positive results regarding
      accessibility and awareness of condoms. However, this often did not lead to the
      desired behavioural change of using condoms in risky sexual interactions. The
      majority of respondents still resisted condom usage, used condoms inconsistently,
      or were not in a position to negotiate protected sexual intercourse. The main
      reasons reported for this were: reduced pleasure, perceived and real physical
      side-effects, myths, lack of information, status, financial reasons, distrust in
      the efficacy of condoms, family planning, cultural reasons, gender-related
      reasons and trust. Many of the barriers to consistent condom use cannot be
      overcome by strategies that target the individual. Interventions need to address
      underlying developmental factors such as the non-biological factors that increase
      the susceptibility of women to HIV infection. As this falls outside of the scope
      of the mandate of the Department of Health, various partnerships with other key
      role players need to be established and/or strengthened, such as with local
      government, non-governmental organisations and faith-based organisations.

PMID- 18709212
TI  - Microcredit for people affected by HIV and AIDS: insights from Kenya.
AB  - Consequences of HIV and AIDS are exponential in Kenya, touching not only the
      health of those infected, but also depleting socioeconomic resources of entire
      families. Access to financial services is one of the important ways to protect
      and build economic resources. Unfortunately, the norm of financial viability
      discourages microfinance institutions from targeting people severely impacted by
      HIV and AIDS. Thus, HIV and AIDS service NGOs have been increasingly getting
      involved in microcredit activity in recent years for economic empowerment of
      their clients. Despite limited human resources and funding in the area of
      microcredit activity, these NGOs have demonstrated that nearly 50% of their
      microcredit beneficiaries invested money in income-generating activities,
      resulting in enhancement to their livelihood security. In the short term these
      NGOs need to improve their current practices. However, this does not mean
      launching microfinance initiatives within their AIDS-focused programmes, as
      financial services are best provided by specialised institutions. Longer-term
      cooperation between microfinance institutions and other AIDS service
      organisations and donors is necessary to master appropriate and rapid responses
      in areas experiencing severe impacts of HIV and AIDS.

PMID- 18709213
TI  - The challenge of the millennium: maternal mortality in Brazil.

PMID- 18709214
TI  - [Assessment of Primary Health care in Brazil: mapping and analysis of research
      conducted and/or financed by the Ministry of Health from 2000 to 2006].
AB  - This article presents a mapping and analysis of monitoring and assessment
      research in Primary Health Care conducted and/or financed by the Ministry of
      Health and completed and published from 2000 to 2006. A total of 109 studies were
      identified, of which 11 had been completed, 84 were ongoing, and 14 had been
      concluded and had published partial results. First, studies from 2000 to 2002
      were addressed to analyze the implementation of the Family Health Program and
      detect its weaknesses, potentialities, and costs. This phase could be described
      as "evaluation for decision-making", emphasizing the views of managers and health
      professionals. Another characteristic was the fragmentation/overlapping of
      studies, often conducted simultaneously and with similar objectives and
      methodologies. Most of the studies were published as technical reports using
      specialized, complicated language. The PROESF baseline studies performed since
      2004 represent a step forward by incorporating elements for overcoming weaknesses
      in previous processes; these new elements include impact assessments,
      methodologies, and results-sharing, involving actors from Municipal and State
      health secretariats, and staff training in evaluation activities, and the
      perspectives of health services users.

PMID- 18709215
TI  - [Estimation of risk areas for hepatitis A].
AB  - This study estimated hepatitis A risk areas in a region of Duque de Caxias, Rio
      de Janeiro State, Brazil. A cross-sectional study consisting of a hepatitis A
      serological survey and a household survey were conducted in 19 census tracts. Of
      these, 11 tracts were selected and 1,298 children from one to ten years of age
      were included in the study. Geostatistical techniques allowed modeling the
      spatial continuity of hepatitis A, non-use of filtered drinking water, time since
      installation of running water, and number of water taps per household and their
      spatial estimation through ordinary and indicator kriging. Adjusted models for
      the outcome and socioeconomic variables were isotropic; risk maps were
      constructed; cross-validation of the four models was satisfactory. Spatial
      estimation using the kriging method detected areas with increased risk of
      hepatitis A, independently of the urban administrative area in which the census
      tracts were located.

PMID- 18709216
TI  - [Diagnosis of the situation with breastfeeding in Piaui State, Brazil].
AB  - This study aims to evaluate the situation with breastfeeding in the State of
      Piaui, Brazil, at the time of the 2006 vaccination campaign. The sample consisted
      of 1,963 infants (< 1 year of age) from 45 municipalities. Medians and
      probabilities of breastfeeding categories were calculated by probit analysis.
      Multivariate logistic analysis was used to analyze the association between
      independent variables and partial and exclusive breastfeeding. The probabilities
      were: 16% for exclusive breastfeeding and 18% for predominant breastfeeding at
      180 days of age and 58% for breastfeeding at 361 days. Median duration was 67
      days for exclusive breastfeeding and 200 days for breastfeeding. The
      breastfeeding rate was higher for children whose mothers belonged to social
      classes C, D, and E (p = 0.024) and lived in the countryside (p = 0.009). Not
      nursing during the first 24 hours of life, using a pacifier, and bottle-feeding
      reduced the prevalence of breastfeeding (p < 0.001). The prevalence rates are
      below the recommended standards and reflect the need to prioritize actions to
      promote breastfeeding in the State.

PMID- 18709217
TI  - [Prescription, dispensing, and regulation of psychoactive anorexigenic drugs in
      Belo Horizonte, Minas Gerais, Brazil].
AB  - This retrospective study in Belo Horizonte, Minas Gerais, Brazil, aimed to
      provide indicators on the sale and consumption of anorexigenic substances. During
      the first stage, 2,906 of 168,237 prescriptions received by pharmacies in 2003
      were analyzed, showing low quality of prescriptions. Projected consumption in
      defined daily doses was 19.75 DDD/1,000 inhabitants/day in 2003. Fenproporex
      (59.8%) was the most widely consumed drug. One pharmacy was responsible for 39.8%
      of the pharmaceutical sales. During the second stage, 14,554 sales records from
      this "blockbuster" pharmacy were analyzed, from April to August 2005; 9.2% of
      sales were for anorexigenic products, 91.8% of which prescribed in association
      with another substance. The data suggest irrational use of anorexigenic drugs by
      these consumers and highlight the need for proper regulation of these products.
      It is important to understand both the role of pharmacies in this regulation and
      that of physicians in the rational use of these substances.

PMID- 18709218
TI  - [Visual, hearing, and physical disability: prevalence and associated factors in a
      population-based study].
AB  - The aim of this study was to describe the prevalence of disabilities according to
      demographic and socioeconomic characteristics, as well as to determine the main
      causes. The research used data from two population-based health surveys in Sao
      Paulo State, Brazil, in 2002 and 2003, designed with complex sampling techniques.
      Interviewees that reported disabilities comprised the study sample, according to
      the database variables. Prevalence of any disability was 110.8; visual
      disability, 62; hearing disability, 44; and physical disability, 13.3. Prevalence
      rates for disabilities varied according to age, gender, and schooling. Prevalence
      of hearing and physical disability was higher among men. The principal cause of
      disabilities was the disease itself. External causes were also one of the
      causative factors in disabilities. Disabilities increased with age and were more
      prevalent among women and persons with less schooling, and the principal causes
      were diseases and injuries.

PMID- 18709219
TI  - [Clinical breast examination during prenatal visits: analysis of coverage and
      associated factors in a city in the State of Rio Grande do Sul, Brazil].
AB  - The Brazilian Ministry of Health recommends that breast examination be performed
      along with breastfeeding orientation during the first prenatal visit. The aims of
      the current study were to analyze breast examination during prenatal care and
      describe the factors associated with insufficient coverage. A cross-sectional
      study was performed in Rio Grande, Rio Grande do Sul State, Brazil, from May to
      July 2007. Data for women who had just given birth were recorded on a
      standardized questionnaire. Of 445 women, 266 (59.8%) had not undergone breast
      examination during prenatal care. Non-white women and those with a monthly income
      below the minimum wage (BRL 380.00) or with prenatal care and delivery in the
      public health system showed the highest probability of not having a breast
      examination during prenatal care. The results show the low prevalence of breast
      examination during prenatal care and indicate serious problems related to quality
      of prenatal care, besides unequal access for poor women.

PMID- 18709220
TI  - [Antimicrobial prescription in family health units in Southern Brazil].
AB  - This paper describes antimicrobial prescription, clinical indications, and
      seasonal characteristics in primary health care. We performed a cross-sectional
      study in family health units in Bage, Rio Grande do Sul State, Brazil, in July
      2005 and January 2006. All medical prescriptions (n = 2,877) were analyzed, and
      the prevalence rates for antimicrobial prescription in winter and summer were
      30.4% (95%CI: 28.5-32.4) and 21% (95%CI: 19.1-22.9), respectively. The most
      frequently prescribed antimicrobials were amoxicillin and sulfamethoxazole
      trimethoprim. The main clinical indications for antimicrobial prescription were
      non-specific upper respiratory tract infections (22.5%), throat infections
      (20.8%), urinary tract infections (13.3%), otitis (8.5%), and sinusitis (7.5%).
      We observed differences between summer and winter in prescriptions for the same
      diseases. Seasonal differences between treatment profiles for the same diseases
      show the absence of a consistent antimicrobial prescription pattern in primary
      health care, contrary to World Health Organization guidelines, which advocate the
      establishment of protocols for antimicrobial use at all levels of care, as a
      strategy to prevent inadequate usage and the occurrence of strains that are
      resistant to available antimicrobials.

PMID- 18709221
TI  - [Portuguese (Brazil) cross-cultural adaptation of the Hwalek-Sengstock Elder
      Abuse Screening Test (H-S/EAST) used to identify risk of violence against the
      elderly].
AB  - This article describes the cross-cultural adaptation, for use in Brazil, of the
      Hwalek-Sengstock Elder Abuse Screening Test (H-S/EAST), used to identify risk of
      domestic violence against the elderly. Evaluating the conceptual and item
      equivalences, the article concludes that they are pertinent in the Brazilian
      context. Semantic equivalence covered the terms' correspondence in
      referential/denotative meaning and the items' general/connotative correspondence
      per se. Measurement equivalence was investigated by means of psychometric
      properties. As with the original instrument in English, the factor analysis
      revealed three dimensions. Six of the seven items loaded satisfactorily in factor
      1 ("situation of potential abuse" scale). Internal consistency proved reasonable,
      with discreet intra-observer reproducibility. The second factor representing the
      dimension of "violation of personal rights or direct abuse" showed similar
      performance. Even so, the study identified an exchange of items between these
      scales and crossed loads. A third scale that was supposed to encompass the
      "characteristics of vulnerability" did not show the same performance. The
      conclusion was that even without demonstrating complete equivalence, the H-S/EAST
      could already be recommended, at least in part, in the Brazilian context.

PMID- 18709222
TI  - [Unified National Health System costs in Sao Jose dos Campos, Sao Paulo State,
      Brazil, for hospital admissions due to external causes].
AB  - The objective of this study was to identify direct expenditures for
      hospitalizations due to external causes in the Unified National Health System
      (SUS) in the city of Sao Jose dos Campos, Sao Paulo State, Brazil. Admissions to
      the Dr. Jose de Carvalho Florence Municipal Hospital resulting from external
      causes or injuries - ICD-10, chapters XIX and XX respectively - were analyzed for
      the first semester of 2003. 976 patient admission forms were analyzed, after data
      evaluation. Admissions with the highest total cost were those resulting from
      motor vehicle accidents and falls. The highest mean cost for hospitalization for
      injury was due to motor vehicle accidents (BRL 614.63), followed by assault (BRL
      594.90). The highest mean cost for hospitalization due to injury was for cervical
      fractures (BRL 1,191.42) and head injuries (BRL 1,000.44). Hospitalizations with
      the highest daily cost were skull and facial fractures (BRL 166.72) and abdominal
      trauma (BRL 148.26). The study confirmed that motor vehicle accidents, falls, and
      assault are an important source of costs due to hospitalization for injuries.

PMID- 18709223
TI  - [Dental and gingival pain and associated factors among Brazilian adolescents: an
      analysis of the Brazilian Oral Health Survey 2002-2003].
AB  - The aim of this study was to estimate the prevalence of dental and gingival pain
      and associated factors among Brazilian adolescents (15-19 years of age). Data
      from 16,126 adolescents who participated in the Brazilian Oral Health Survey SB
      Brazil 2002-2003 were used. The outcome measured was dental and gingival pain in
      the last six months. Independent variables were per capita income, schooling,
      school enrollment, gender, skin color, age, area of residence, time since last
      dental appointment, type of dental service, DMFT index and its components, dental
      calculus, and Dental Aesthetic Index. Simple and multiple Poisson regression
      analyses were performed. Prevalence of dental and gingival pain was 35.6% (95%CI:
      34.8-36.4). Increased prevalence of pain was associated with: female gender, low
      income, non-students, students enrolled in public schools, and grade-for-age lag.
      In addition, adolescents with high levels of dental caries and dental calculus
      also reported higher prevalence of dental pain. Dental and gingival pain can be
      considered a relevant public health problem, suggesting the need for preventive
      measures.

PMID- 18709224
TI  - [Profile of the elderly population in two poor municipalities in North and
      Northeast Brazil: the results of a cross-sectional population-based survey].
AB  - This study aimed to determine the profile of the elderly population (>or= 60
      years) in two poor municipalities in North and Northeast Brazil in 2005. Using a
      cross-sectional survey with a systematic sample, previously trained interviewers
      applied a standard household questionnaire on demographic characteristics,
      socioeconomic status, household conditions, physical activity, immunization
      status, health problems, and expenditures on medicines. Of the total sample (n =
      1,013), 528 lived in Caracol, Piaui State, and 478 in Garrafao do Norte, Para
      State. 56% were 60-69 years old, 10% lived alone, 69% were illiterate, 8% had a
      family income less than the minimum wage, 24% of the households had a flush
      toilet, 60% had a radio, television, and refrigerator, 88% reported at least one
      chronic disease, 47% had to purchase all their medicines out-of-pocket, 84% had
      received influenza vaccination, and 90% were able to perform normal activities of
      daily living. Elderly people included in this study showed poor household
      conditions, inadequate access to health care, and high levels of morbidity.

PMID- 18709225
TI  - [Oral health and daily performance in adults in Chapeco, Santa Catarina State,
      Brazil].
AB  - The use of subjective indicators in dentistry has been increasing. This was a
      population-based cross-sectional study in the city of Chapeco, Santa Catarina
      State, Brazil, analyzing the relationship between oral health conditions and
      quality of life in 35-44-year-old adults (n = 622). A further objective was to
      observe the influence of habits, dental visits, self-evaluation of health status,
      and socio-demographic characteristics in this process. The sample was selected
      using a multiple-stage approach. Trained professionals collected the data. A
      multiple non-conditional, hierarchical logistic regression model was used to
      analyze the determinants of low (Oral Impact on Daily Performance - OIDP <or= 3)
      and high (OIDP >or= 10) interference of oral health in daily routine. The
      response rate was 81%. Oral health status was found to interfere in the daily
      routine of 20.7% of participants and was more severe for 11.4%. Household
      crowding, low-income neighborhoods, female gender, and orofacial pain in the
      previous six months were associated with higher interference in quality of life.
      The use of subjective indicators in public health services planning and
      definition of priority groups for delivery of oral health services is highly
      recommended.

PMID- 18709226
TI  - [Childbirth practices and challenges for humanization of care in two public
      hospitals in Southern Brazil].
AB  - The aim of this study was to characterize hospital care for childbirth in two
      hospitals affiliated with the Unified National Health System in Maringa, Parana,
      Brazil, and identify both obstacles and facilitating factors for the
      implementation of humanized care, based on women's perception of the care
      received. This was an exploratory and descriptive study with a cross-sectional
      design, analyzing hospital patient charts and interviews with 569 women who gave
      birth at the two hospitals from March 2005 to February 2006. Hospital care was
      characterized on the basis of WHO quality-of-care guidelines for labor and
      delivery. The data pointed to a healthcare model marked by the hygienist legacy
      in physician-centered hospital protocols and professional practices.
      Institutional factors, identified as difficulties in institutional and
      infrastructure organization, hospital protocols, and health professionals'
      individual practices and stances, denote barriers that jointly hinder the
      implementation of a humanized model for childbirth care.

PMID- 18709227
TI  - [Development of a questionnaire to evaluate sugar abuse and dependence].
AB  - This study describes the development of a questionnaire to evaluate the potential
      abuse of (and dependence on) non-milk extrinsic sugar (NMES). Recent studies have
      shown that excessive NMES consumption can cause alterations in the central
      nervous system due to the influence of these substances in the neurochemical
      reward system. The questionnaire was originally developed from a summary of
      reports from four focus groups utilizing the "L" module of the MINI-Plus
      questionnaire. Addiction specialists subsequently evaluated the draft of the
      questionnaire and altered the original instrument's content, substituting terms
      in order to better fit the substance used in this study. However, the original
      structure of 20 questions on abuse and dependence was maintained. It is hoped
      that an instrument to evaluate NMES abuse and dependence will help health
      professionals prevent and treat problems related to over-consumption of sugars.
      However, the diagnosis of sugar abuse and dependence and the instrument's
      potential psychometric properties require further study by the scientific
      community.

PMID- 18709228
TI  - [Analysis of the implementation of a mobile pre-hospital treatment system in five
      Brazilian state capitals].
AB  - The article presents a description and analysis of the implementation of a pre
      hospital treatment system (SAMU) as part of the research project Diagnostic
      Analysis of the Implementation of a National Policy for the Reduction of Violence
      and Accidents. Implementation and organization of the SAMU service, together with
      the related materials, human resources, and equipment, was studied in five
      Brazilian State capitals with high morbidity and mortality rates from external
      causes: Curitiba (Parana), Recife (Pernambuco), Brasilia (Federal District), Rio
      de Janeiro, and Manaus (Amazonas). The study involved four phases, each
      developing exploratory and analytical cycles, combined with fieldwork,
      triangulating quantitative and qualitative data. Implementation of the pre
      hospital treatment system is now a key health sector asset. Further necessary
      steps include: comprehensive legislation covering vehicles, personnel, and
      equipment; closer networking between mobile units and healthcare facilities;
      focus on information generated in this sub-system, thus facilitating planning;
      and maintaining and upgrading high qualifications for SAMU crews. The service is
      officially establishing, standardizing, and regulating a sub-system that is
      crucial for saving lives.

PMID- 18709229
TI  - [Health in the prison system: representations and practices by prison guards in
      Rio de Janeiro, Brazil].
AB  - The role of prison guards in limiting access to health services by inmates and
      the impact of their representations on daily health practices were investigated
      through an action-research program. The program aimed to produce knowledge and
      improve the guards' involvement in tuberculosis and HIV/AIDS control by raising
      their awareness. Developed in three prisons and two hospitals, the study included
      individual interviews and group discussions and showed that representations of
      health and illness, risk hierarchy, and preventive strategies are related to
      actors' status in the prison's social organization, the conflicts and tensions
      between them, and the sense of group belonging that reinforces identities and
      antagonisms. Such representations have a major influence on the guards' daily
      practices and inmates' access to health services. The denial of inmates' right to
      health and their limited autonomy contributed to the implementation of
      essentially prescriptive health actions. The guards' awareness of their own
      health representations and practices may contribute to the deconstruction of
      stereotypes and increase their involvement in prevention and care. Further,
      improvement of inmates' health depends on changes in prison conditions.

PMID- 18709230
TI  - [Semantic equivalence of the Brazilian version of the Early Childhood Oral Health
      Impact Scale].
AB  - The North American instrument Early Childhood Oral Health Impact Scale (ECOHIS)
      was created to assess the oral health-related quality of life of preschool
      children and their families. Its use in Brazil requires prior cultural
      adaptation, and semantic equivalence is one step in this process. The objective
      of this study was to evaluate the semantic equivalence between the ECOHIS and its
      Brazilian version. The methodology included six steps: translation of the ECOHIS
      into Portuguese, done by two translators; a pre-test, in which the two
      translations were tested in a group of 20 parents/guardians of children 2-5 years
      of age; unification of the two versions; two back-translations done independently
      by two translators; review of the translations and back-translations; and
      production of a final version of the questionnaire. The two translated versions
      were very similar, and after completion of all steps a final version of the
      ECOHIS was obtained. The use of translations and back-translations carefully
      evaluated by experts and incorporating suggestions from the target population
      allowed the development of a Brazilian version of the ECOHIS that is semantically
      equivalent to the original instrument.

PMID- 18709231
TI  - [Proposal for a hierarchical framework applied to investigation of risk factors
      for neonatal mortality].
AB  - Theoretical-conceptual models aim to integrate social, biological, behavioral,
      and other factors and to explain their interrelations in the determination of
      health outcomes. In the case of determination of neonatal death in Brazil, few
      studies have analyzed the mechanisms by which numerous variables and constructs
      interrelate. This article offers a theoretical discussion of the possible
      components of a hierarchical framework for studying neonatal mortality. The
      proposed model sought to include factors that have traditionally been identified
      as relevant to the occurrence of neonatal death and others that have been studied
      more recently (like race, social support, and violence during pregnancy). The
      components were distributed in 11 dimensions allocated to four hierarchical
      levels (one distal, two intermediary, and one proximal). The proposed framework
      should be adjusted to the Brazilian reality for neonatal death in large cities
      and raises various aspects for discussion that have not been explored previously
      in Brazil.

PMID- 18709232
TI  - [Development of children enrolled in preschools in Cuiaba, Mato Grosso State,
      Brazil].
AB  - The aim of this study was to assess the neuropsychomotor development of children
      enrolled in daycare centers and preschools. This cross-sectional study used 38
      items from the Denver II test to assess four and five-year-olds enrolled in the
      municipal school system in Cuiaba, Mato Grosso State, Brazil, from August 2002 to
      November 2003. There were 960 children enrolled in 27 daycare centers and two
      public preschools. Statistical analysis used the chi2 test with a 95% confidence
      interval and alpha = 5%. Logistic regression was used to calculate the
      percentages with which the preschoolers passed the test at each respective age.
      Of the 960 preschoolers tested, 67% showed normal performance, 30.2% borderline,
      and 2.8% abnormal. In 27 of the 38 items, the proportion of correct answers was
      greater than 90%. Altered performance was more common in five-year-old boys.
      Performance in this sample was quite similar to that of preschoolers in Denver,
      Colorado, USA. The best results by gender were for girls, and by age in four-year
      olds.

PMID- 18709233
TI  - [Profile of motorcycle accident victims treated at a public hospital emergency
      department].
AB  - The number of accidents involving motorcycles has increased in Brazil. The
      objective of this study was to identify the type of victims of these accidents
      who were treated at an emergency department in Piaui State, Brazil. The sample
      included 430 such victims in this quantitative study. Most were male, 15-24 years
      of age, and from the State of Piaui itself. 301 of the victims were drivers of
      the motorcycles, 81 were passengers, and 48 were struck or run over by the
      motorcycles. 76.05% of the accidents occurred from Thursday to Sunday. 80.75% had
      temporary sequelae, and 53.33% of the accidents occurred at night. In 69.3% of
      the cases, victims suffered lacerations; 51.4% fractures; 27.44% hematomas; and
      20.7% head trauma. Among the accident victims, motorcycle drivers, and those
      suspected of alcohol consumption, 52.07% were not wearing a helmet at the time of
      the accident. Most of the victims were discharged from hospital, while 14 died.
      In conclusion, injuries from motorcycle accidents deserve attention, especially
      to plan preventive measures to help control their occurrence in the State.

PMID- 18709234
TI  - [Epidemiological profile of domestic violence: complaints of aggression filed in
      a city in Sao Paulo State, Brazil, from 2001 to 2005].
AB  - The aim of this study was to analyze complaints of household physical aggression
      filed in Aracatuba, Sao Paulo, Brazil, from 2001 to 2005. The study described the
      social characteristics of aggressors and victims, their family relationship,
      locale, time of day, day of week, causes of aggression, kind of injuries, and use
      of alcohol/drugs by aggressor. Of 7,750 complaints of aggression, 1,844 involved
      domestic violence: 81.1% involved the spouse or partner (group A), 11.6%
      parents/guardians and children (group B); and 7.3% other family members (group
      C). In the three groups, the aggressions occurred mainly at home, and the
      aggressors were mostly males. In group A, aggressions occurred mainly on weekends
      (38.9%), with jealousy as the most frequently reported cause (21.5%). In group B,
      children/adolescents constituted 68.1% of the victims, mostly girls, while 5.2%
      of victims were 60 years old. All three groups involved mostly minor injuries
      like bruises and excoriations to the head and upper limbs. Aggressors were
      frequently under the influence of alcohol: 26.8% (group A), 21.6% (group B),
      17.1% (group C). Drug use was probably underestimated in the three groups (2.2%,
      1.8%, and 4.5%, respectively).

PMID- 18709235
TI  - Effectiveness of daily and weekly iron supplementation in the prevention of
      anemia in infants.
AB  - OBJECTIVE: To evaluate the effectiveness of universal prophylactic targeting with
      iron sulfate on daily or weekly basis in the prevention of anemia in infants.
      METHODS: Randomized clinical field trial with children between ages six and 12
      months seen at primary health care units in the municipality of Rio de Janeiro,
      Brazil, between 2004 and 2005. Three concurrent cohorts were compared: daily
      group (n=150; 12.5mg Fe/day); weekly group (n=147; 25mg Fe/week) and control
      group. The intervention consisted of universal supplementation with iron sulfate
      for 24 weeks, combined with educational adherence-promoting measures. OUTCOME:
      mean serum hemoglobin concentration, distribution and prevalence of anemia
      (Hb<110.0 g/l) at age 12 months. Effectiveness was evaluated considering both
      intent to treat and adherence to protocol, using multiple regression analysis
      (linear and Poisson). RESULTS: Groups were homogeneous in terms of descriptive
      variables. The intervention was implemented successfully, with high adhesion to
      protocol in both groups, and no statistical difference between them. After
      adjustment, only the daily regimen showed a protective effect. Adherence analysis
      demonstrated an evident dose-response effect on mean Hb and prevalence of anemia
      only for the daily regimen. No protective effect was detected for the weekly
      regimen. CONCLUSIONS: Universal supplementation with iron sulfate from six to 12
      months of age was effective in increasing serum Hb and decreasing risk of anemia
      only when administered on a daily basis.

PMID- 18709236
TI  - [Validity of indicators of physical activity and sedentariness obtained by
      telephone survey].
AB  - OBJECTIVE: To assess the reliability and validity of indicators of physical
      activity and sedentariness obtained by means of a telephone-based surveillance
      system. METHODS: Reliability and validity studies were carried out in two random
      subsamples (n=110 and n=111, respectively) obtained from the total sample
      (N=2,024) of adults (> or =18 years) studied by the system in the municipality of
      Sao Paulo in 2005. Studied indicators included frequency of "sufficiently active
      during leisure time," "inactive in four domains of physical activity (leisure,
      work, transportation, and housework)," and "habit of watching television for long
      periods." Reliability was assessed by comparing results of the original telephone
      interview with those of another identical interview repeated after seven to 15
      days. Validity was assessed by comparing the results of the telephone interview
      with those of three 24-hour recalls (reference method) carried out in the week
      following the original interview. RESULTS: Frequencies obtained for of the three
      evaluated indicators were either identical or very similar for the first and
      second telephone interviews. Kappa coefficients ranged from 0.53 to 0.80,
      indicating good reliability for all indicators. In relation to the reference
      method, all indicators showed 80% or higher specificity, and sensitivity values
      were 69.7% for "watching television for long periods," 59.1% for "inactive in
      four domains," and 50% for "sufficiently active during leisure." CONCLUSIONS: The
      indicators of physical activity and sedentariness included in the system seem
      reliable and sufficiently accurate. If kept operational in coming years, this
      system may provide Brazil with a useful instrument for evaluating public policies
      aimed at promoting physical activity and controlling non-transmissible chronic
      diseases associated with sedentariness.

PMID- 18709237
TI  - [Validity of food and beverage intake data obtained by telephone survey].
AB  - OBJECTIVE: To evaluate the reproducibility and validity of data on food and
      beverage intake obtained by means of a telephone-based surveillance system.
      METHODS: Reproducibility and validity analyses were carried out in two random
      subsamples (n=112 and n=119, respectively) of the total sample (N=2,024) of
      adults (> or =18 years) studied by the system in 2005 in the municipality of Sao
      Paulo, Southeastern Brazil. Indicators evaluated included protective factors
      (daily or almost daily intake of fruit and vegetables) and risk factors (daily or
      almost daily intake of soft drinks, frequent intake of foods containing saturated
      animal fat, and abusive intake of alcoholic beverages) for the development of
      chronic diseases. Reproducibility was studied by comparing the results of the
      original telephonic interview with those of another interview carried out 7-15
      days later. Validity was analyzed by comparing the results of the telephone
      interview with those of three 24-hour recalls (our gold-standard) carried out up
      to 5 days following the original interview. RESULTS: The frequency of the studied
      indicators remained relatively constant between the first and second telephone
      interviews, with kappa coefficients ranging from 0.57 to 0.80, indicating good
      reproducibility for all indicators. In relation to the gold standard, there was a
      trend towards overestimating the frequency of intake of protective foods, but of
      foods associated with increased risk of chronic diseases. Sensitivity and
      specificity were high for indicators of consumption of risk-associated foods
      (close to 80%), and variable in the case of protective foods (42% to 80%).
      CONCLUSIONS: The evaluation showed evidence of good reproducibility and adequate
      validity for most indicators employed in the system, which indicates that
      maintaining this system operational in coming years will provide a useful
      instrument for evaluating public policies for the promotion of a healthy diet and
      for control of non-communicable chronic diseases with a dietary component in
      Brazil.

PMID- 18709238
TI  - Comorbidity adjustment index for the international classification of diseases,
      10th revision.
AB  - OBJECTIVE: To develop a Charlson-like comorbidity index based on clinical
      conditions and weights of the original Charlson comorbidity index. METHODS:
      Clinical conditions and weights were adapted from the International
      Classification of Diseases, 10th revision and applied to a single hospital
      admission diagnosis. The study included 3,733 patients over 18 years of age who
      were admitted to a public general hospital in the city of Rio de Janeiro,
      southeast Brazil, between Jan 2001 and Jan 2003. The index distribution was
      analyzed by gender, type of admission, blood transfusion, intensive care unit
      admission, age and length of hospital stay. Two logistic regression models were
      developed to predict in-hospital mortality including: a) the aforementioned
      variables and the risk-adjustment index (full model); and b) the risk-adjustment
      index and patient's age (reduced model). RESULTS: Of all patients analyzed, 22.3%
      had risk scores > or = 1, and their mortality rate was 4.5% (66.0% of them had
      scores > or = 1). Except for gender and type of admission, all variables were
      retained in the logistic regression. The models including the developed risk
      index had an area under the receiver operating characteristic curve of 0.86 (full
      model), and 0.76 (reduced model). Each unit increase in the risk score was
      associated with nearly 50% increase in the odds of in-hospital death.
      CONCLUSIONS: The risk index developed was able to effectively discriminate the
      odds of in-hospital death which can be useful when limited information is
      available from hospital databases.

PMID- 18709239
TI  - [Physical violence and associated factors: a population-based study in Southern
      Brazil].
AB  - OBJECTIVE: To estimate the prevalence of physical violence and its association
      with sociodemographic aspects, stressful life events, and the use of health
      services due to emotional problems. METHODS: A cross-sectional population-based
      study was conducted with a sample of 1,954 14-year-old or older inhabitants of
      the city of Canoas (Southern Brazil). They were selected by means of conglomerate
      sampling according to a pre-established system. Data were obtained in visits to
      households by means of a confidential semi-structured questionnaire. A bivariate
      analysis was carried out through multinomial logistic regression, and the
      multivariate analysis by polytomous logistic regression, categorizing the outcome
      by age group. RESULTS: The findings show a prevalence of 9.7% (CI 95%:
      8.37;11.03) and association with: women 20 years old and older (OR=2.74; CI 95%:
      1.52;4.94); higher schooling rate (p<0.03); higher experience of stressful life
      events at 20 years of age or more (OR=6.61; CI 95%: 2.71;16.1); and doctors'
      appointments due to emotional problems as of 10 years of age (p>0.001).
      CONCLUSIONS: The prevalence of physical violence in the population was
      significant, resulting in important emotional consequences and impact on health
      services, requiring capacity building of the professionals in the field.

PMID- 18709240
TI  - [Work-related diseases and health-related compensation claims, Northeastern
      Brazil, 2000].
AB  - OBJECTIVE: To estimate the contribution of work-related diseases to sick leaves
      due to general and occupational health problems. METHODS: Sociodemographic,
      occupational and health data from 29,658 records of temporary disability
      benefits, granted on account of health problems by the Instituto Nacional do
      Seguro Social (National Institute of Social Security) in the state of Bahia
      (Northeastern Brazil), were analyzed. All constant ICD-10 clinical diagnoses were
      taken into consideration, except for those referring to external causes and
      factors that influence contact with health services. The link between diagnosis
      and occupation was based on the ICD-10 code and whether the type of compensation
      was due to a "work-related accident/disease" or not. RESULTS: From all the
      benefits, 3.1% were granted due to work-related diseases: 70% were
      musculoskeletal system and connective tissue diseases, while 14.5% were related
      to the nervous system. In general, benefits granted at more than two times the
      expected frequency were as follows: tenosynovitis in the manufacturing sector
      (Proportion Ratio-PR=2.70), carpal tunnel syndrome in the financial
      intermediation sector (PR=2.43), and lumbar disc degeneration in the
      transportation, postal service and telecommunications sectors (PR=2.17). However,
      no causal connection could be established for these diseases, in these activity
      sectors, in a significant percentage of benefits. CONCLUSIONS: Results suggest
      the existence of possible occupational risk factors for diseases in these fields
      of activity, as well as the underreporting of the link between diseases and work,
      thus disguising the responsibility of companies and the perspective of prevention
      through work reorganization.

PMID- 18709241
TI  - [Survival after motor vehicle crash: impact of clinical and prehospital
      variables].
AB  - OBJECTIVE: To assess clinical and prehospital variables associated with survival
      of motor vehicle crash victims. METHODS: Study carried out in the city of Sao
      Paulo (Southeastern Brazil), from 1999 to 2003. Data from 175 patients, who were
      aged between 12 and 65 years and had been motor vehicle crash victims, were
      analyzed. Kaplan-Meier Survival Analysis was used to approach the results at the
      accident scene with victims scoring <11, according to the Revised Trauma Score.
      Variables analyzed were: sex, age, injury mechanisms, basic and advanced support
      procedures, Revised Trauma Score parameters and fluctuations, time elapsed in the
      prehospital phase and trauma severity according to the Injury Severity Score and
      Maximum Abbreviated Injury Scale. RESULTS: Analysis revealed that victims who
      were less likely to survive during the hospitalization period showed serious
      lesions in the abdomen, thorax, or lower limbs, with negative fluctuation of
      respiratory frequency and Revised Trauma Score in the prehospital phase. In
      addition, they needed specialized interventions or thoracic compressions. Brain
      lesions were associated with late death. CONCLUSIONS: Recognition of variables
      involved in the survival of motor vehicle crash victims may help to determine
      protocols and to make decisions in order to perform pre- and in-hospital
      interventions and, consequently, maximize survival.

PMID- 18709242
TI  - Spatial analysis of urban violence based on emergency room data.
AB  - OBJECTIVE: To estimate the spatial intensity of urban violence events using
      wavelet-based methods and emergency room data. METHODS: Information on victims
      attended at the emergency room of a public hospital in the city of Sao Paulo,
      Southeastern Brazil, from January 1, 2002 to January 11, 2003 were obtained from
      hospital records. The spatial distribution of 3,540 events was recorded and a
      uniform random procedure was used to allocate records with incomplete addresses.
      Point processes and wavelet analysis technique were used to estimate the spatial
      intensity, defined as the expected number of events by unit area. RESULTS: Of all
      georeferenced points, 59% were accidents and 40% were assaults. There is a non
      homogeneous spatial distribution of the events with high concentration in two
      districts and three large avenues in the southern area of the city of Sao Paulo.
      CONCLUSIONS: Hospital records combined with methodological tools to estimate
      intensity of events are useful to study urban violence. The wavelet analysis is
      useful in the computation of the expected number of events and their respective
      confidence bands for any sub-region and, consequently, in the specification of
      risk estimates that could be used in decision-making processes for public
      policies.

PMID- 18709243
TI  - [Level of physical activity and smoking in undergraduate students].
AB  - OBJECTIVE: To evaluate the level of physical activity in undergraduate students
      and to investigate its potential association with smoking. METHODS: A cross
      sectional study with a stratified sample proportional to the total number of
      students was carried out in Gurupi, Central-West Brazil, in 2005. The sample
      comprised 871 subjects. The IPAQ-8 short version was applied to assess the level
      of physical activity. Smoking status was evaluated by a modified World Health
      Organization (WHO) questionnaire and the magnitude of smokers' nicotine
      dependence was quantified using the Fagerstrom nicotine dependence scale. The
      frequencies, prevalences and prevalence ratios were determined by Yates' chi
      square test or Fisher's exact test in the entire sample and stratified by area,
      course, shift and gender, with a 5% statistical significance level. RESULTS: Mean
      age was 25 years old (SD+/-8) and mean age at first smoking experience was 17
      years old (SD+/-4). The prevalence of physical inactivity and smoking was 29.9%
      and 7.2%, respectively. The overall prevalence of sedentary smokers and non
      smokers was 8.5%, and 91.5%, respectively, but the difference was not
      statistically significant. A higher prevalence of smoking and physical inactivity
      was found in those over 25 (48.6%, p <0.05). Nicotine dependence was "very low"
      in most subjects (68.2%, p <0.05). Smoking was more prevalent in males (10.8%, p
      <0.05) and the level of physical inactivity was not different in both males and
      females (p >0.05). CONCLUSIONS: Physical inactivity was seen on both smokers and
      non-smokers in the same proportion and no association was found between these two
      variables. Low prevalences of physical inactivity and smoking found in the study
      may be explained by available ongoing preventive and education programs, which
      should be implemented in the long run.

PMID- 18709244
TI  - [Bordetella pertussis in adolescent students in Mexico City].
AB  - OBJECTIVE: To estimate seroprevalence of Bordetella pertussis in students and
      their community. METHODS: A total of 12,273 adolescent students aged 12 to 15
      years from 14 public high schools in Mexico City were studied from September 2002
      to March 2003. Nasopharyngeal samples were collected from those adolescents with
      whooping cough for more than 14 days. Infection was confirmed using polymerase
      chain reaction (PCR). All students, school staff and family exposed to PCR
      confirmed cases were tested. RESULTS: Whooping cough rate was 5 to 1,000
      students. Of those students (61) who were identified with whooping cough for more
      than 14 days, 20 (32.8%) were positive to Bordetella pertussis. Of 152 people
      exposed (contacts) to these cases, 16 (10.6%) were positive and only eight (50%)
      had whooping cough. One of these exposed (contacts) was the principal of a school
      that had more than 60% positive cases (12/20) and who was also a teacher of 10
      infected students. Of 29 family members tested, eight (27.6%) were positive and
      from three different families. CONCLUSIONS: The study results show a similar rate
      of whooping cough in adolescents as seen in other countries. Since persistent
      cough is not always clinically seen in all infected individuals, there may be
      asymptomatic cases of Bordetella infection.

PMID- 18709245
TI  - [Utilization of oral health care for Down syndrome patients].
AB  - OBJECTIVE: From a perspective of comprehensive care, the purpose of the study was
      to evaluate factors associated to dental care provided to Down syndrome children
      and adolescents. METHODS: A cross-sectional study was carried out including 112
      pairs of mothers/Down syndrome children aged between 3 and 18 years who attended
      a public hospital genetics clinic in Rio de Janeiro, Southeastern Brazil, in
      2006. Dental care was not provided at the clinic. Data were collected through a
      questionnaire administered to the mothers and oral examinations of their
      children. Multiple logistic regression was used for data analysis. The dependent
      variable was "dental care of the Down syndrome child or adolescent" and the
      independent variables included demographic, socioeconomic and behavioral
      characteristics. RESULTS: Most children (79.5%) had had at least one dental visit
      (90% CI: 72.3; 87.8). Dental experience of the children was associated to the
      following variables: mothers who reported being advised by their children's
      health provider to take them to the dentist's (OR=6.1 [2.5; 15.1]); children with
      prior history of surgery (OR=2.5 [0.9; 7.1]); and age between 12 and 18 years
      (OR=13.1 [2.0; 86.9]). CONCLUSIONS: Dental care provided to Down syndrome
      children and adolescents was associated to advice given by their health
      providers, a part of comprehensive care.

PMID- 18709246
TI  - [Inequalities in access to health care services and utilization for the elderly
      in Sao Paulo, Brazil].
AB  - OBJECTIVE: To describe factors associated to inequalities in access to health
      care services and utilization for the elderly. METHODS: Study part of the Health,
      Well-being and Aging in Latin America and the Caribbean ("SABE") Survey that
      included 2,143 elderly individuals aged 60 or older in the city of Sao Paulo,
      southeastern Brazil, in 2000. A two-step sampling procedure with probability
      proportional to size was carried out using census tracts with replacement. To
      achieve the desired number of respondents aged 75 or older, additional households
      close to the selected census tracts were sampled. Access to health services and
      utilization were measured for outpatient and hospital services during a 4-month
      period prior to the interview, and correlated to factors related to ability, need
      and predisposition (total income, schooling, health insurance, reported medical
      condition, self-perception, gender and age).Multivariate logistic regression was
      performed in the analysis. RESULTS: Of all respondents, 4.7% reported being
      hospitalized and 64.4% seeking outpatient care in the four months prior to the
      study. As for public outpatient care provided, 24.7% were in hospital clinics and
      24.1% in other public outpatient services. As for private care, 14.5% received
      care in hospitals and 33.7% in health clinics. The multivariate analysis showed
      an association between health service utilization and sex, medical condition,
      self-perceived health, income, schooling, and health insurance. However, an
      inverse effect was found for the variable "schooling". CONCLUSIONS: The study
      results show inequalities in access to health services and utilization as well as
      a deficient health care system. Public policies should take into account the
      specific needs of the elderly population to facilitate access to health care
      services and reduce inequalities.

PMID- 18709247
TI  - [Development and validation of a multidimensional questionnaire assessing non
      adherence to medicines].
AB  - The study aimed to develop and validate an instrument capable of measuring non
      adherence to drug treatment in its multiple dimensions. The Questionario de
      Adesao a Medicamentos (Adherence to Medicines Questionnaire) with three questions
      was applied to 46 people with arterial hypertension in the city of Blumenau,
      Southern Brazil, in 2006. Non-adherence measures obtained were compared to four
      other methods (Haynes, Morisky, pill count and clinical outcome). Non-adherence
      measures varied according to the method. The combined Questionario de Adesao a
      Medicamentos non-adherence measure was 47.8% (95% CI: 32.9;63.1), whereas the
      gold standard was 69.6% (95% CI: 54.3;82.3). Accuracy measures to detect non
      adherence showed a sensitivity of 62.5% and specificity of 85.7%, ROC curve area
      of 74.1%, and positive predictive value of 90.9%. Results suggest the
      Questionario de Adesao a Medicamentos has a good fit.

PMID- 18709248
TI  - [Congenital syphilis and syphilis during pregnacy].

PMID- 18709249
TI  - [Health research in Brazil].

PMID- 18709251
TI  - Pulmonary hypertension secondary to coronary-to-pulmonary artery fistula.
AB  - The coronary fistula is an anomaly characterized by the communication between a
      coronary artery and a cardiac chamber, pulmonary artery, coronary sinus and
      pulmonary veins. It represents 0.2 to 0.4% of the congenital cardiopathies and
      0.1% to 0.2% of the adult population submitted to coronary angiography. We report
      the clinical case of a 64-year-old female patient, whose anomaly was diagnosed
      during a clinical investigation due to chest discomfort, dyspnea and syncope; the
      surgical correction was indicated, with opening of the pulmonary artery through
      extracorporeal circulation.

PMID- 18709252
TI  - Quadricuspid aortic valve by transthoracic echocardiography.
AB  - A 55-year-old woman seeks medical attention with palpitations, atypical chest
      pain and dyspnea upon exertion, lasting for 12 months. ECG showed left
      ventricular hypertrophy. Transthoracic Doppler echocardiogram confirmed
      hypertrophy of the left chambers and showed a quadricuspid aortic valve, with
      equal-sized cusps, in addition to a moderate regurgitant central flow. Upon
      echocardiography, the quadricuspid valve is identified by its characteristic "X"
      form during diastole and rectangular aspect during systole. Heart failure
      symptoms are presumably caused by valve insufficiency due to abnormal leaflet
      coaptation. Considering the possibility of progressive regurgitation, follow up
      on the patient was performed with periodic echocardiographic control. Symptoms
      responded to treatment.

PMID- 18709253
TI  - Patent ductus arteriosus: endovascular treatment in adult patient.
AB  - The patent ductus arteriosus (PDA) is a common type of congenital heart defect
      and its correction is simple when performed early in life. Surgery is performed
      using stitches or clips. In adults, the anomaly can lead to pulmonary
      hypertension and ventricular dysfunction. Surgery in adults is controversial and
      high-risk. This report describes an alternative endovascular approach in an adult
      patient.

PMID- 18709255
TI  - Cardioverter-defibrillator in the primary prevention of sudden death: for all or
      for a few?

PMID- 18709254
TI  - Three-dimensional echocardiography in patient with mitral valve prolapse.

PMID- 18709256
TI  - Surgery for aortic valve endocarditis: treatment options for aortic abscess.
AB  - BACKGROUND: Patients with infective endocarditis show a large diversity of
      anatomical presentations, which has been a complicating factor for the surgical
      treatment of this condition, especially in those who develop abscesses in the
      aortic ring or intracardiac fistulae. For this reason, surgeons have been
      developing tactical options to repair it. There is consensus around the fact that
      the removal of infected tissue promotes radical cleaning, and that the outcome of
      the treatment has been improved by the manufacture of biological glues which
      facilitate the closure of abscesses and by the creation of new valve
      replacements. OBJECTIVE: To demonstrate yet one more treatment option for aortic
      abscess for selected cases: a valved conduit placed in infra-coronary position.
      METHODS: We employed the technique in three patients: in two of them we employed
      a valved conduit with a mechanical prosthesis and in one of them a valved conduit
      with a biological prosthesis. Two patients needed associated procedures such as
      replacement of mitral valve in one of them and tricuspid valvoplasty in the
      other. All cases involved reoperation of prostheses in aortic position. RESULTS:
      The progression during surgery and in the early postoperative period was
      satisfactory and the three patients were discharged from the Intensive Care Unit
      and were sent to hospital rooms. One of the patients progressed to death during
      hospital stay due to severe comorbidities which were present in the preoperative
      period, and which related to esophageal varices and hepatic involvement. The
      other two progressed well in the late postoperative period. CONCLUSION: We
      believe that this option is yet one more alternative for the treatment of
      abscesses with great involvement of aortic ring structures and mitro-aortic
      continuity.

PMID- 18709257
TI  - Changes in pulmonary function after surgical treatment of congenital heart
      disease with pulmonary hyperflow.
AB  - BACKGROUND: Analysis of pulmonary status of pediatric patients in the
      postoperative phase of cardiac surgery. OBJECTIVE: To assess pulmonary compliance
      and airway resistance in patients with congenital heart disease and pulmonary
      hyperflow submitted to surgical treatment with the use of extracorporeal
      circulation. METHODS: Thirty-five patients were evaluated during surgery with
      measurements of static compliance and airway resistance at four different
      timepoints. Pulmonary measurements were performed non-invasively using end
      inspiratory airway occlusion and specific mathematical formulas. The variables
      examined and related to pulmonary changes were: preoperative - age, weight, and
      relationship between systemic and pulmonary blood flow; intraoperative -
      perfusion times, anoxia times and minimum temperature; postoperative - time on
      mechanical ventilation and length of stay in the intensive care unit. RESULTS:
      Pulmonary compliance in all patients had an immediate and significant increase
      (P<0.001) at the end of surgery. Patients older than 30 months experienced a
      greater increase (P=0.0004). Those with more than 10 kg also had a greater
      increase (P=0.0006). In patients on extracorporeal circulation for more than 50
      minutes, the increase in pulmonary compliance took longer to occur (P=0.04).
      Airway resistance was not significantly changed at the end of surgery (P=0.393).
      CONCLUSION: All patients experienced improved pulmonary compliance at the end of
      surgery, and this was significantly influenced by age, weight and time on
      extracorporeal circulation. Airway resistance, however, was not changed.

PMID- 18709258
TI  - Tissue Doppler imaging as a long-term prognostic index in left ventricular
      systolic dysfunction.
AB  - BACKGROUND: Tissue Doppler parameters correlate with left ventricular (LV)
      filling pressure and can be useful as prognostic indexes for patients with heart
      failure. OBJECTIVE: Determine whether tissue Doppler parameters can predict
      events during long term follow-up of outpatients with LV systolic dysfunction.
      METHODS: Retrospective study with 73 patients (aged 60.9+/-12.1 years) who
      underwent Doppler echocardiogram between March 2001 and May 2004. The primary
      endpoint studied was death or hospitalization due to heart failure worsening.
      RESULTS: The mean follow-up period was 1,367+/-665 days. After logistic stepwise
      multivariate analysis, including echocardiographic parameters, the ratio of
      maximal early diastolic filling wave velocity to maximal early diastolic
      myocardial velocity (E/E; ratio; p=0.0007), and LV ejection fraction (EF; p=0.01)
      remained significant predictors of the primary outcome. The optimal cutoffs for
      primary endpoint prediction for E/E' ratio (AUC 0.77; p=0.0001) and EF (AUC 0.68,
      p=0.006) were respectively 12.7 and 30%. Accordingly, patients with E/E' ratio >
      12.7 (hazard ratio=3.8, p =0.001) or EF <30% (hazard ratio=2.3, p=0.03) had a
      poorer outcome by survival curve analysis. It is noteworthy that 47% of the
      patients with EF above the optimal cutoff point, but with high E/E' ratio,
      presented events during follow-up. CONCLUSION: E/E' ratio is an important
      independent long-term prognostic index of death or hospitalization due to
      worsening heart failure in outpatients with LV systolic dysfunction. Therefore,
      we recommend the measurement of this variable in the routine evaluation of such
      patients.

PMID- 18709259
TI  - Excess weight, arterial pressure and physical activity in commuting to school:
      correlations.
AB  - BACKGROUND: The prevalence of obesity and elevated arterial pressure (AP) has
      increased in children and adolescents, whereas physical activity has decreased.
      OBJECTIVE: To identify and correlate excess weight, body fat and elevated AP
      among active and passive students with the way they commute to school. METHODS:
      One thousand five hundred and seventy students aged 7 to 12 years participated in
      the study conducted in Joao Pessoa, state of Paraiba. Students completed a
      questionnaire about the way they commuted to school (active = walking/biking or
      passive = by car/motorcycle/bus) and the time spent traveling to school. Excess
      weight was determined by BMI > or =25 kg/m(2), excess body fat as > or =85th
      percentile for tricipital fold measurement, and high AP as > or =90th percentile.
      Chi-square test and Poisson's regression were used for the analysis. RESULTS:
      Active commuting was associated with a lower prevalence of excess weight and body
      fat as compared to passive commuting (p<0.05). The prevalence ratio (PR) of
      excess weight was associated with excess body fat (Male: PR= 6.45 95%CI= 4.55
      9.14; Female: PR= 4.10 95%CI= 3.09-5.45), elevated SAP [Systolic Arterial
      Pressure] (Male: PR= 1.99 95%CI= 1.30-3.06; Female: PR= 2.09 95%CI= 1.45-3.01),
      and elevated DAP [Diastolic Arterial Pressure] in girls (PR = 1.96 95%CI= 1.41
      2.75). No association with active commuting was observed (p>0.05) CONCLUSION:
      Passive commuting to school showed a correlation with excess weight and body fat
      but not with elevated AP. Excess weight was associated with excessive body fat
      and elevated AP. Excess weight should be prevented as a way to avoid fat
      accumulation and AP elevation.

PMID- 18709260
TI  - Brazilian version of a lifestyle questionnaire: translation and validation for
      young adults.
AB  - BACKGROUND: Inappropriate lifestyles have been responsible for the leading causes
      of mortality. The purpose of the Fantastic Lifestyle Questionnaire is to help
      physicians involved in health prevention to identify and assess their patients'
      lifestyles. OBJECTIVE: To translate and validate the Fantastic Lifestyle
      Questionnaire for use with young adults. METHODS: The process of translation into
      Portuguese and validation consisted of four steps: 1) translation; 2) correction
      and semantic adaptation by professional experts (judges); 3) content validation;
      and 4) a final evaluation by the target population. The statistical analyses used
      were Cronbach's alpha to measure internal consistency reliability, intra-class
      correlation coefficient (R) for external consistency, and the Kappa index to test
      construct validity. RESULTS: Cronbach's alpha coefficient measured the
      correlation between items and the total was 0.69, which is considered reasonable
      for an instrument designed to evaluate a latent variable that can only be
      estimated and not measured. When the items were grouped into domains, it was
      possible to verify that they all contributed equally to the stability of the
      questionnaire (alpha=0.60). The external consistency evaluated by intra-class
      correlation was R=0.92 (p=0.2), which demonstrates a high degree of
      reproducibility; the construct validity of 4 and 3 categories was 75 and 80.7%
      with Kappa indices of 0.58 and 0.7, respectively, which show an excellent
      discriminatory classificatory capacity. CONCLUSION: The Fantastic Lifestyle
      Questionnaire has an adequate internal and external consistency for evaluating
      young adult lifestyles, and it can be recommended for primary care and
      epidemiological studies.

PMID- 18709261
TI  - Association between hypertension and overweight in adults in Belem, state of Para
      (Brazil), 2005.
AB  - BACKGROUND: Hypertension is a major public health issue affecting 20 to 25% of
      the global population of adults, and 12 to 35 % of Brazilians. OBJECTIVE: To
      evaluate the association between hypertension and overweight. METHODS: A cross
      sectional study was conducted in 2005 with a probabilistic sampling of the
      population >18 years of age in Belem, capital of the state of Para, in the
      Northern region of Brazil, using the telephone surveillance system for chronic
      diseases (SIMTEL). The dependent variable was hypertension, the explanatory
      variable was overweight and the confounding variables were age, level of
      education and lifestyle characteristics. The variables associated with
      hypertension were run through the regression logistic model and odds ratios were
      calculated for each variable. RESULTS: Hypertension affected 16.2% of men and
      18.3% of women, and overweight affected 49.2% of men and 34.1% of women. The
      prevalence of hypertension was directly associated with age and overweight in
      both genders. Among men, hypertension was associated with intake of vegetables
      and low intake of beans (similar to kidney- and pinto-type beans); as for women,
      hypertension was associated with marital status (widow or separated), and
      inversely to education level. The risk of hypertension increased directly with
      weight for both genders (p<0.001), and it was 6.33 times higher among obese men
      and 3.33 among obese women as compared to normal-weight subjects. CONCLUSION:
      Overweight was associated with hypertension. However, variables such as age,
      education, and food consumption interfere in this relationship, creating
      circumstances favorable to reducing or increasing that risk.

PMID- 18709262
TI  - Positive end-expiratory pressure and renal function influence B-type natriuretic
      peptide in patients with severe sepsis and septic shock.
AB  - BACKGROUND: Myocardial dysfunction is a complication associated with a poor
      prognosis in septic patients. A biomarker of cardiac function providing
      prognostic information is of paramount interest. OBJECTIVE: We sought to
      determine the value of B-type natriuretic peptide in patients with severe
      sepsis/septic shock. METHODS: We performed a prospective study in patients with
      severe sepsis/septic shock in a medical intensive care unit. B-type natriuretic
      peptide level was determined within 24 hours after the diagnosis of severe
      sepsis/septic shock. We also analyzed mortality, and presence of association
      between B-type natriuretic peptide and clinical, hemodynamic and respiratory
      variables. RESULTS: 23 (9 women; 14 men) patients with ages ranging from 20-79
      (mean 51.3+/-18.6) years old and APACHE score of 22.6+/-11.8 were included; 15
      (65.2%) patients received pulmonary artery catheters, and 20 (87%) were
      mechanically ventilated. Multivariate analysis disclosed inverse association
      between B-type natriuretic peptide values with positive end-expiratory pressure
      values, and direct association with creatinine (beta 0.548 and 0.377, p 0.02 and
      0.002, respectively), but not with mortality, clinical and hemodynamic
      parameters. CONCLUSION: This is the first report on an inverse association
      between positive end-expiratory pressure and BNP levels in patients with severe
      sepsis and septic shock. BNP and creatinine levels should be taken into
      consideration when analyzing B-type natriuretic peptide levels in this setting.

PMID- 18709264
TI  - BELIEF: believe it or not.

PMID- 18709263
TI  - Magnetic resonance vs technetium-99m pyrophosphate scintigraphy in the detection
      of perioperative myocardial necrosis.
AB  - BACKGROUND: Perioperative myocardial infarction (POMI) is a complication of
      coronary artery bypass grafting (CABG) with a potential prognostic impact.
      Technetium-99m pyrophosphate myocardial scintigraphy (MS) is used in the
      diagnosis of POMI; however it shows a limited sensitivity for subendocardial
      lesions. Cardiovascular magnetic resonance imaging (CMRI), in turn, has a high
      accuracy in the detection of myocardial necrosis. OBJECTIVE: To compare CMRI and
      MS for the detection of POMI after CABG. METHODS: A total of 24 patients with
      chronic coronary artery disease were studied using the delayed contrast enhanced
      CMRI and MS before and after CABG by analyzing the development of areas of
      perioperative myocardial necrosis (POMI). Biochemical markers of myocardial
      injury (CKMB and troponin I) were also determined before and after surgery.
      RESULTS: Nineteen patients completed the study. Of these, 6 (32%) presented POMI
      on CMRI and 4 (21%) on MS (p = NS). Of the 323 left ventricular segments
      assessed, 17 (5.3%) showed perioperative necrosis on CMRI and 7 (2.2%) on MS (p =
      0.013). Moderate agreement was observed between the methods (kappa = 0.46). There
      was disagreement regarding the diagnosis of POMI in 4 (21%) cases, most of them
      with small areas of perioperative necrosis on CMRI which were not visualized on
      MS. In all cases with POMI on CMRI, significant CKMB and troponin I elevations
      were observed. CONCLUSION: Moderate diagnostic agreement was observed between the
      methods for the detection of POMI, but CMRI enabled visualization of small areas
      of perioperative myocardial necrosis which were not identified on MS and were
      associated with elevation of biochemical markers of myocardial injury.

PMID- 18709265
TI  - Levosimendan in patients with decompensated heart failure.

PMID- 18709266
TI  - Case 4/2008 - a 15-year-old male adolescent with accentuated isthmic coarctation
      of the aorta.

PMID- 18709267
TI  - Developing competencies for drug demand reduction.

PMID- 18709268
TI  - Stressful situations in life, use and abuse of alcohol and drugs by elderly in
      Monterrey, Mexico.
AB  - This is a descriptive, qualitative, and correlation study with 112 elderly aged
      60 years or older. This study aimed to identify differences in alcohol
      consumption according to gender and marital status, and differences in the
      consumption of medical drugs by gender. It also aims to determine differences in
      stressful life events by gender, and differences in stressful life events
      associated to alcohol and medical drugs use and abuse, as well as to know their
      perceptions on the most stressful life events they have experienced. The results
      showed significant differences in alcohol consumption by gender (U=154.0, p
      <0.01), in which the consumption was higher for men. It was reported that the
      medical drugs consumption (C2 =5.95, p <0.15) and life stress indexes (U=1038.5,
      p =0.10) are higher for women. The most stressful life events reported were:
      their health problems or those of their relatives, family and economic problems.

PMID- 18709269
TI  - Benzodiazepine use among employees of a private company.
AB  - This study aimed to identify variables associated to the consumption of
      benzodiazepine among workers of a private company in the VIII Region, Chile. This
      is a cross-sectional and correlative study. STUDY POPULATION: 40 employees of a
      private company. The instruments included a questionnaire on socio-demographic
      variables and a benzodiazepine questionnaire. There was no record of
      benzodiazepine consumption at the moment of the study. Twenty percent (20%) of
      the interviewees had already used benzodiazepine in the past, whereas, half of
      them (10%) in the last year. The bivariate analysis of the last year consumption
      of benzodiazepine with work hours variables showed no significant relation
      (p=0.073). No association was found between benzodiazepine consumption and socio
      demographic variables among the study participants.

PMID- 18709270
TI  - Drugs use by six to seven-year-old children from an elementary school in Celaya,
      Guanajuato, Mexico.
AB  - This study aimed to identify the use of drugs by six to seven-year-old students
      from an elementary school in Celaya, Gto., Mexico. It is a cross-sectional
      exploratory study with non-probabilistic sample. Thirty-nine students, both
      genders, were interviewed, and the use of drugs was identified, not only among
      students, but also among people close to them. The whole sample (100%) was 7
      years old, 61.5% female, 77% reported their mothers smoked, and 25% she consumed
      alcohol; 24.3% reported their father smoked, and 48.6% he consumed alcohol; 30.6%
      of the scholars had already consumed alcohol once (beer), 8.1% had tried
      cigarettes, but not other drugs.

PMID- 18709271
TI  - Alcohol effects on family relations: a case study.
AB  - Problems related to alcohol abuse have been associated to different factors,
      regardless of the causes attributed to this phenomenon. Alcohol consumption and
      dependence is considered a public health problem and deserve attention because of
      the social, work, family, physical, legal and violence-related risks it
      represents. This study aimed to identify the effects of alcoholism on family
      relations and, by means of case management, to encourage the recovery of these
      relationships. The results show that the problems caused by alcohol abuse impose
      profound suffering to family members, which contributes to high levels of
      interpersonal conflict, domestic violence, parental inadequacy, child abuse and
      negligence, financial and legal difficulties, in addition to clinical problems
      associated to it.

PMID- 18709272
TI  - Meanings regarding the use of alcohol in families of a Venezuelan poor community.
AB  - This study is the result of an ethnographic research based on interpretative
      anthropology. It aims to interpret the meanings of alcohol misuse in families
      from a poor Venezuelan community. Twenty members from six families participated
      in the study. The results show differences between meanings children and parents
      held regarding alcohol consumption. Children held a more positive view, whereas
      mothers presented the lowest acceptation of alcohol consumption. Meanings were
      more convergent than divergent, which allowed the identification of the following
      units: excessive consumption, intoxication, and joy. The association of alcohol
      with parties and joy is the main motivation to drink and the main barrier to
      change drinking habits. Two units of meaning were identified: a continuum between
      normal and pathologic drinking; and concept of joy subordinated to alcohol
      consumption.

PMID- 18709273
TI  - Alcohol, alcoholism and alcohol addicts: conceptions and attitudes of nurses from
      district basic health centers.
AB  - This qualitative study aimed to learn the conceptions and attitude tendencies of
      nurses from public district basic health units towards alcohol, alcoholism and
      alcohol addicts. The sample consisted of ten nurses from three institutions in a
      city located in Sao Paulo. Data were recorded and submitted to content thematic
      analysis. Subjects evidenced that these nurses are permissive towards moderate
      alcohol use, but reject alcoholism, conceiving it as a potentially fatal disease,
      and tend to associate it to personal will, indicating the influence of the moral
      concept on their conceptions and attitudes. The participating nurses' knowledge
      about the topics alcohol and alcoholism was also evidenced. Based on the results,
      the authors suggest training this group and preparing these professionals for the
      care, recognition and prevention of disorders related to alcohol use/abuse at
      these health centers.

PMID- 18709274
TI  - Perceptions of adolescents students on the consumption of drugs: a case study in
      Lima, Peru.
AB  - The consumption of drugs has increased worldwide and has become a public health
      problem, affecting particularly adolescents. This study aimed to identify the
      opinions of adolescent students on the use of drugs and drug users, in a school
      in Lima, Peru. It is a descriptive and cross-sectional study with a questionnaire
      self-applied to 386 students. Data collected comprised students' personal data,
      their perception on the risk of drugs consumption, motivations, information on
      preventive interventions, drugs availability, opinion regarding drug users and
      their family, and social acceptance. Male gender was predominant. Most of the
      participants were unfavorable regarding risk perception and consumption motives,
      though, they were favorable towards information. We have a relevant role in
      explaining behaviors and also in implementing appropriate and efficient
      preventive and treatment programs.

PMID- 18709275
TI  - Consumption of energy drinks among physical education students.
AB  - This descriptive and cross-sectional study aimed to characterize the pattern of
      energy drinks consumption in a sample of physical education students through a
      self-applied questionnaire (socio-demographic data and characterization of
      consumption). Variables associated with consumption: gender, marital status,
      attending gym classes, athletic swim practice, and study in the morning.
      Consumption pattern (n=137): 2.2% once in their lives, 9.5% at least once in the
      last 12 months, 38% at least once in the last month, 39.4% six times or more in
      the last month, 10.9% 20 times or more in the last month. Justification for
      consumption: 54% to improve the taste of alcoholic drinks, 27.7% to extend their
      evening leisure periods, 13.9% to improve sports performance, 9.5% for
      stimulation, 8.8% enjoy the taste, 6.6% for curiosity and 4.4% to study. Of those
      who consumed energy drinks, 87.6% mixed it with alcohol, and 25.9% of the
      students reported they consume more alcohol when it is mixed with energy drinks.
      CONCLUSIONS: the consumption of energy drinks is associated to sports and
      drinking alcohol.

PMID- 18709276
TI  - Nursing students' work, a risk factor for the consumption of alcohol and other
      drugs.
AB  - This descriptive, qualitative study aims to describe risk factors, in the work
      environment, for the consumption of alcohol and other drugs, and also to confirm
      the importance of protective factors. Interview technique was used with 51
      nursing students at the Rio de Janeiro State University, who work in the city's
      health services. RESULTS: students related work as a risk factor for the
      consumption of drugs such as alcohol, cigarettes and anxiolytics. We conclude
      that working with participative methodologies, valuing student's former
      experiences, family and group life, and individual characteristics are essential
      in the preventive approach. Attention to protective factors is recommended.

PMID- 18709277
TI  - Undergraduate students' motivations for the consumption of legal drugs.
AB  - This qualitative research aimed at identifying conceptions held by undergraduate
      students regarding the term motivation, and motives leading them to the
      consumption of legal drugs. Data were collected through a questionnaire with four
      open questions, applied to 15 students of a public university in the central
      region of Mexico. In order to perform the data analysis, answers were classified
      in two categories: a) Undergraduate students' conceptions regarding the term
      motivation and b) Undergraduate students' conceptions regarding the motives for
      consumption. Such analysis indicated that students identify two types of
      motivations: external and internal. The external motivation includes family, mass
      media and friends; whereas internal motivation includes personal characteristics,
      need of belonging, curiosity, pleasure and idleness.

PMID- 18709278
TI  - Nursing students' premature pregnancy and consumption of alcohol.
AB  - This qualitative descriptive research aimed to analyze pregnancy dynamics,
      experienced by a group of women who, at the time, were at most 19 years old, and
      identify the role attributed to the consumption of alcohol in such dynamics. The
      research was developed with a group of 20 students from the Colombia National
      University. Six of them were selected for in dept investigation through
      interviews, which were analyzed by content analysis. Based on the literature and
      the subjects' life history, the study examines the following categories:
      pregnancy, making love, maternity, being a woman, and drinking. Through these
      categories, was possible to identify the dynamics experienced by these women
      during pregnancy.

PMID- 18709279
TI  - Alcohol consumption by nursing students in Honduras.
AB  - The recreational use of alcohol is very frequent in the life of college students.
      A descriptive study was carried out with nursing students in Honduras, where the
      use of psychoactive substances represents a considerable health problem,
      especially the use of alcohol. This study identified that 74.9% were abstinent.
      Nevertheless, the study focused on drinkers, whose consumption pattern may be
      changing over time. According to the sample characteristics, most subjects were
      young working women, students, and Christians. These variables should be
      considered in the investigation of protective factors against drinking, and in
      designing preventive actions in the university context.

PMID- 18709280
TI  - School as a "protective factor" against drugs: perceptions of adolescents and
      teachers.
AB  - This study aims to discover and describe protective factors regarding the use of
      drugs, according to teachers and students, aged 14 to 15 years, from a Public
      Secondary School in Santiago de Queretaro, Mexico. This is a descriptive and
      exploratory study. Data collection was carried out through semi-structure
      interview and non-participative observation with ten students and five teachers.
      Three themes resulted from data analysis: school and school's environment: the
      school does not provide a healthy environment; use of drugs: perceived by both
      the students and teachers in the institution itself; prevention programs: there
      are health promotion and prevention programs available at the school. According
      to the students' and teachers' perceptions, the school represents a risk factor.

PMID- 18709281
TI  - Drug consumption by medical students in Tegucigalpa, Honduras.
AB  - The use of drugs, in Honduras, involves 25% of college students. The most used
      substances include legal and recreational drugs, such as alcohol. This study
      aimed to identify the use of drugs and socio-demographic factors in a sample of
      260 medical students. RESULTS: Average age of 20 years old, unemployed and
      religious women, single, with no children. Alcohol was the most consumed drug in
      the last six months for recreational purposes. The following stimulants were
      frequently consumed: caffeine, mate herb tea, energetic drinks and Coke. Drugs
      like marijuana, cocaine, valium and sedatives were used in smaller proportions.
      The reasons reported by women were: to alleviate tiredness and improve their
      academic performance. The men's reasons were recreation and to alleviate
      psychological tension. This research has implications for the development of
      drugs prevention programs in universities.

PMID- 18709282
TI  - Teachers' social representations on drug use in a secondary school.
AB  - Increased concern regarding drug abuse among adolescents contributes to the
      elaboration of prevention programs at schools. This investigation aims to know
      teachers' social representations, regarding drug abuse, in a secondary school in
      Florianopolis, SC, Brazil. A total of 16 teachers of the 5th to 8th grades
      participated in the study. Data were collected through associations elaborated by
      teachers in response to the expression: drugs use/abuse. The teacher's
      representations are organized around a central concept - the vulnerable other: a
      needy adolescent, who becomes drugs user, highlighting the family, everyday
      coping, and the school's (in)visibility in prevention actions, as factors
      related. The complexity of factors involving drugs production, distribution and
      its commercialization, demands the implementation of actions that go beyond the
      scopes of education and health. The elaboration of inter-sector prevention
      programs considering local characteristics is necessary.

PMID- 18709283
TI  - Nursing students' perception regarding predicting factors of drugs use.
AB  - The study on the perception of 264 (33.2%) nursing students from the
      Professionalization and Regular groups regarding predicting factors of drugs
      consumption shows these students consume alcohol and tobacco and view alcohol as
      a leading factor in the consumption of drugs. The Professionalization group
      consumes tranquilizers and stimulants at a higher rate than the Regular group.
      The Professionalization students argue that they have to deal with an excessive
      personal load: career, job, family and stress. According to them, these factors
      motivate the consumption of tranquilizers and stimulants. The Professionalization
      group views the family and religion as protective factors; friends and school, on
      the other hand, are considered risk factors. Both groups consider drug users as
      amoral and addicts. The present study provides indicators that can support real
      actions aimed at improving the education of nursing personnel.

PMID- 18709284
TI  - Self-esteem, perceived self-efficacy, consumption of tobacco and alcohol in
      secondary students from urban and rural areas of Monterrey, Nuevo Leon, Mexico.
AB  - This study aimed to know the differences, if any, in the consumption of tobacco
      and alcohol among adolescents from urban and rural areas, and if self-esteem and
      self-efficacy are related to the consumption in these two groups of adolescents
      from secondary schools in urban and rural areas of Nuevo Leon Mexico, from
      January to June in 2006. The study was based on the theoretical concepts of self
      esteem, perceived self-efficacy and consumption of alcohol and tobacco. The
      design was descriptive and correlational with a sample of 359 students. A
      substantial difference was found in the consumption of tobacco among secondary
      students from urban and rural areas (U= 7513.50, p = .03). The average
      consumption in urban area was higher (average chi = .35) than in the rural area
      (average chi = .14). A negative and significant relation was found between the
      quantity of drinks consumed on a typical day and self-esteem (r s = - .23, p
      <.001), as well as for the quantity of cigarettes consumed on a typical day (r s
      = - .20, p <.001).

PMID- 18709285
TI  - Perceptions of drugs benefits and barriers to quit by undergraduate health
      students.
AB  - Several studies have exposed the consumption of drugs by undergraduate students
      in the health area, who are supposed to be examples of behavior and health
      educators. This descriptive correlation study aimed to relate the benefits of
      tobacco consumption and barriers to quit according to the perception of
      undergraduate students. Eighty third-year students, in three different courses,
      answered a self-applied questionnaire. The studied variables were: consumption
      conditions, barriers and benefits regarding drug consumption, family and personal
      characteristics. One-third of the students reported tobacco use; 5% reported the
      use of marijuana; 15% alcohol and 6% tranquilizers, more than once a month; 18%
      reported the consumption of tobacco and 13% reported the use of alcohol even
      before the age of 15. The perceived benefits were: relaxation, pleasure and
      social acceptance, whereas barriers for quitting were: habituation and addiction.
      According to the results, promoting self-responsibility of these future health
      professionals is recommended in their educational context.

PMID- 18709286
TI  - Conceptions of nursing students on health promotion related to psychoactive
      substances.
AB  - This qualitative study aimed to investigate the perception of undergraduate
      nursing students on health promotion in view of the use of psychoactive
      substances. Nine undergraduate students, attending the last disciplines of the
      first semester, participated in the study and were divided in two focal groups.
      The theoretical-methodological referential was based on Paulo Freire's theory of
      conscientization. Data were processed through content analysis, demonstrating
      that students find difficulties in planning intervention strategies in health
      promotion in view of the drug phenomenon, because the knowledge provided by the
      university has a biologist tendency, typical of the medical model, recognizing a
      gap between theory and practice. Nevertheless, they manage to reconstruct their
      knowledge and become aware of their role as future health promoters in the face
      of drug use and abuse.

PMID- 18709287
TI  - Consumption of benzodiazepines without prescription among first-year nursing
      students at the University of Guayaquil, school of nursing, Ecuador.
AB  - This study aimed to determine the consumption of benzodiazepines without
      prescription among first-year students from a nursing school of a public
      University in Ecuador. This is a descriptive, transversal and explanatory study
      with a quantitative approach. A questionnaire was used for data collection. The
      population studied was of 181 students. The results showed that 10.5% of the
      students had consumed benzodiazepine without prescription once in their lives. Of
      these, 6.1% consumed benzodiazepine in the last year, and 3.9% are currently
      consuming it. The diazepam was the most consumed BZD without prescription and
      pharmacies, were the place of higher access. The main reasons for the
      benzodiazepine consumption were: insomnia, anxiety, stress, depression, family
      and economical problems. The use of benzodiazepines with non-medicinal purposes
      is related to problems such as memory loss, retirement syndrome and sedation.
      When benzodiazepines are consumed jointly with alcohol or other drugs they can
      lead to coma or death. This study shows the serious consequences benzodiazepines
      cause when used by nursing students in Ecuador.

PMID- 18709288
TI  - The search for equality: representations of the smoking act among adolescent
      women.
AB  - This study aimed to discover the representations of the smoking habit in both non
      smoking and smoking female adolescents from a high school in Queretaro, Mexico.
      It is a qualitative research, carried out with 14 female adolescents in 2005. A
      semi-structured interview and a socioeconomic survey were used to collect data.
      Results evidenced adolescents know the biomedical discourse, which proposes that
      smoking causes serious consequences to health. However, there are other symbolic
      reasons that influence its use such as the search for equality and image, since
      they think men find smoking women more attractive and mature. Peer pressure
      represents an important factor for women to smoke by validating its practice and
      minimizing its effects to the body.

PMID- 18709289
TI  - Skin aging.
AB  - There are two main processes that induce skin aging: intrinsic and extrinsic. A
      stochastic process that implies random cell damage as a result of mutations
      during metabolic processes due to the production of free radicals is also
      implicated. Extrinsic aging is caused by environmental factors such as sun
      exposure, air pollution, smoking, alcohol abuse, and poor nutrition. Intrinsic
      aging reflects the genetic background and depends on time. Various expressions of
      intrinsic aging include smooth, thinning skin with exaggerated expression lines.
      Extrinsically aged skin is characterized by photo damage as wrinkles, pigmented
      lesions, patchy hypopigmentations, and actinic keratoses. Timely protection
      including physical and chemical sunscreens, as well as avoiding exposure to
      intense UV irradiation, is most important. A network of antioxidants such as
      vitamins E and C, coenzyme Q10, alpha-lipoic acid, glutathione, and others can
      reduce signs of aging. Further anti-aging products are three generations of
      retinoids, among which the first generation is broadly accepted. A diet with lot
      of fruits and vegetables containing antioxidants is recommended as well as
      exercise two or three times a week.

PMID- 18709290
TI  - Cytokine concentrations in basal cell carcinomas of different histological types
      and localization.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant skin tumor.
      Cytokines as major mediators of the immune system have been shown to play an
      important role in biology of the neoplasm with the general predomination of Th2
      cytokines, whereas IFN-? and other Th1 cytokines are prevalent in spontaneously
      regressing tumors. OBJECTIVE: We were interested in comparing cytokine levels in
      BCC and cutaneous squamous cell tumors with BCC of different localization and
      histological subtypes. MATERIAL AND METHODS: Explants from freshly excised BCC
      from 18 patients, and cutaneous squamous cell tumors (solar keratoses and Bowen's
      disease) from 9 patients were cultivated for 24 h. Cytokine (IL- 2, IFN-gamma, IL
      4, IL-5, IL-6, IL-8, IL-10, IL-12, TNFalpha, IL-1beta) concentrations in culture
      supernatants were determined by a sandwich immunoassay. RESULTS: Tissue explants
      of BCC contained significantly higher concentrations of IL-1beta, IL-4, IL-5, and
      IL-6 compared to those of squamous cell tumors. Higher levels of TNF-alpha (p =
      0.042), IL-4 (p = 0.028), and IL-5 (p = 0.012) were found in tumors localized to
      the head and neck compared to those on the trunk or extremities. Interleukin-6
      concentrations were higher in aggressive BCC variants (infiltrative and
      micronodular), but the difference was not statistically significant (p = 0.068).
      CONCLUSIONS: Confirming the earlier findings that BCC is a tumor with a Th2
      cytokine microenvironment, this study further shows that BCC situated on the head
      and neck produce even more of certain Th2 cytokines (IL-4 and IL-5) and TNF
      alpha, a crucial immunosuppressive cytokine released upon UVB irradiation.

PMID- 18709291
TI  - Contact hypersensitivity to selected excipients of dermatological topical
      preparations and cosmetics in patients with chronic eczema.
AB  - OBJECTIVE: 1) Assessment of the frequency of contact sensitization to selected
      excipients of dermatological topical preparations and cosmetics in patients with
      chronic eczema. 2) Detection of the sources of sensitization. METHODS: 1,927
      patients with chronic eczema (mean age 44.3 years, 601 males, 1,326 females) were
      patch tested with selected excipients. RESULTS: The main rates of sensitization
      observed were: thiomersal 11.3%, wool alcohols 4.0%, phenylmercuric acetate 3.1%,
      formaldehyde 2.5%, dodecyl gallate 2.0%, Bronopol 1.9%, dibromodicyanobutane/
      phenoxyethanol (1:4) 1.7%, chloracetamide 1.6%, chlorhexidine digluconate 1.5%,
      Kathon CG 1.4%, parabens 1.1%, diazolidinyl urea 0.9%, imidazolidinyl urea 0.7%,
      benzalkonium chloride 0.7%, and Quaternium-15 (quaternary ammonium salt) 0.7%.
      CONCLUSION: The rate of sensitization to the excipients included in
      dermatological topical preparations and cosmetics in patients with chronic eczema
      is significant. Complete information on all the ingredients is necessary.

PMID- 18709292
TI  - Multiple cutaneous bronchogenic cysts located on the neck and the scalp. A case
      report.
AB  - Bronchogenic cyst is a benign congenital developmental abnormality of the
      embryonic foregut. The skin is a rare site for bronchogenic cysts, and in this
      location it is often a solitary lesion. It is poorly recognized by clinicians and
      in almost all cases the diagnosis is established by histopathologic examination.
      This report documents a new case of multiple cutaneous bronchogenic cysts
      bilaterally located on the neck and on the scalp, which are unusual locations of
      this lesion.

PMID- 18709293
TI  - Amelanotic malignant melanoma in an acral location.
AB  - We present the case of a 74-year-old white female admitted to the Department of
      Dermatology because of a tumor in the IV-V interdigital area of her right foot. A
      crimson, dome-shaped tumor with a granular, spongy surface (diameter 4 cm) had
      developed over a period of about 3 months. The biopsy, stained with H and E,
      revealed an anaplastic malignant tumor. Additional immunochemical staining with
      Melan A allowed us to make the final diagnosis: amelanotic malignant melanoma
      (MM). The melanoma was removed by amputation of digits IV and V, with partial
      removal of the metatarsal bones (Clark degree 5, Breslow thickness 9 mm).
      Sentinel node biopsy was done using Tc99; it revealed no neoplastic alteration.
      The patient is still under oncological observation.

PMID- 18709294
TI  - Unilesional mycosis fungoides treated with photodynamic therapy. A case report.
AB  - BACKGROUND: Mycosis fungoides, or cutaneous T-cell lymphoma (CTCL), is one of the
      most common skin lymphomas, with a chronic and lethal course. It is characterized
      by the expansion of CD4+ and CDw29+ immunophenotype T-cell clones lacking normal
      antigens. These altered T-lymphocytes are predominantly located in the skin, but
      some of them retain their ability to migrate and exit the skin through the
      lymphatics into the circulatory system. CASE REPORT: We report on a 78-year-old
      man with an 8-year history of histologically verified Mycosis fungoides. Twenty
      five years ago, the patient was incorrectly diagnosed with psoriasis vulgaris and
      received therapy with only slight effect. In 1999 the patient underwent full body
      actinotherapy (30 Gy) which resulted in complete remission of CTCL lesions on the
      skin. In October 2005 the patient presented at our department with a new
      partially infiltrated lesion 14x6 cm in his right groin. Because
      photochemotherapy and local therapy with corticosteroids had already been used
      without significant results, we opted for photodynamic therapy (PDT) with methyl
      aminolevulinate (MAL).

PMID- 18709295
TI  - Urticaria pigmentosa. A case report.
AB  - We present the case of 22-month-old boy with Urticaria pigmentosa. Clinical
      feature was presented as disseminated yellow-brownish patches, on the skin of
      entire body, including skin of the scalp, 1x2 cm in diameter. No subjective
      symptoms were present. First skin lesion occurred in the second month of life.
      Darier's sign was positive. Serum triptase levels were elevated. Diagnosis of
      mastocytosis was confirmed by pathohistology.

PMID- 18709296
TI  - Cutaneous larva migrans in two Slovenian travelers returning from Brazil.
AB  - Cutaneous larva migrans is a frequent phenomenon endemic in tropical and
      subtropical countries. In Europe only sporadic cases are reported. We present two
      cases of cutaneous larva migrans in two Slovenian tourists returning from a
      vacation in Brazil.

PMID- 18709297
TI  - Penile shaft involvement in pityriasis versicolor.
AB  - The Malassezia yeasts are among the normal human cutaneous flora in adults. They
      are also reported as part of the microflora of male genital region, mostly in
      uncircumcised males. The prevalence of Malassezia yeast colonization on the glans
      penis of circumcised males is discussed in multiple studies. We report the case
      of a male patient with extensive pityriasis versicolor that does not involve the
      preputial space.

PMID- 18709298
TI  - A study of the mu opioid receptor gene polymorphism A118G in patients with
      primary biliary cirrhosis with and without pruritus.
AB  - The increase in opioidergic tone by the central administration of morphine, which
      binds to the mu opioid receptor, is associated with pruritus. Pruritus is a
      symptom of cholestasis, which appears to result, in part, from increased
      opioidergic tone; a central mechanism has been proposed. The single nucleotide
      polymorphism Al18G in exon 1 of the opioid receptor mu 1 (OPRM1) gene, which
      codes for the mu opioid receptor, has been associated with alterations in
      functions mediated by the endogenous opioid system. In this study we found A118G
      in heterozygosity in 29% of the DNA samples from patients with primary biliary
      cirrhosis from the USA and from Italy with and without pruritus. A118G was 1.5
      times more frequent in the samples from patients without pruritus from the USA
      than in the rest of the samples. The possibility of protection from pruritus
      associated with A118G supports the study of genetic polymorphisms of the OPRM1
      gene in patients with cholestasis.

PMID- 18709299
TI  - In vitro and in vivo characterization of a novel liposomal butorphanol
      formulation for treatment of pruritus.
AB  - As yet no transdermal topical formulations have been developed for the treatment
      of chronic itch. We developed a formulation containing 2 mg butorphanol tartrate
      in 100 microl purified water encapsulated into multilamellar phospholipid
      vesicles. Drug permeation experiments were studied with Franz diffusion chambers
      using human skin in vitro and on rat skin in vivo. Histological analysis of rat
      skins was performed to evaluate skin irritation of the formulation in vivo.
      Physical properties showed stable formulation with desirable viscosity. In vitro
      dermal penetration rate data suggest that there was significant permeation at
      time-points 2 h and 4 h, and a steady state was achieved afterwards to 24 h.
      Maximal plasma butorphanol concentration was noted at 2 h and steady state was
      achieved at 8 h. Visual skin assessment as well as histological analysis of
      excised rat skin did not demonstrate any evidence of inflammation and irritation.
      In vitro and in vivo analysis demonstrated release of a consistent amount of
      butorphanol in a sustained manner for 24 h. This liposomal transdermal delivery
      formulation could serve as a method to deliver butorphanol for patients with
      chronic pruritus.

PMID- 18709300
TI  - Frequency of bacteria, Candida and malassezia species in balanoposthitis.
AB  - Balanoposthitis is an inflammatory disorder of the prepuce and glans penis.
      Microbes involved in balanoposthitis have been investigated, but no single study
      has covered the growth of both bacteria, Candida and Malassezia. We report here
      the prevalence of these microbes in 100 patients with balanoposthitis and in 26
      control patients. Among patients with balanoposthitis there was a significantly
      higher frequency of positive cultures than in the control group (59% and 35%,
      respectively, p<0.05). In the balanoposthitis group Staphylococcus aureus was
      found in 19%, group B streptococci in 9%, Candida albicans in 18% and Malassezia
      in 23% of patients. In the control group S. aureus was not found at all, whereas
      C. albicans was found in 7.7% and Malassezia in 23% of patients. Different
      microbes did not correspond with distinct clinical manifestations. In summary, we
      report increased frequency of microbes, specifically S. aureus, in the area of
      the prepuce and glans penis in balanoposthitis.

PMID- 18709301
TI  - Inflammation and hypercoagulable state in adult psoriatic men.
AB  - Hyperhomocysteinaemia is a well-known risk factor for cardiovascular disease and
      plays a role in atherothrombosis. Psoriasis is a common chronic and recurrent
      inflammatory skin disease associated with increased thrombosis. The aim of this
      study was to examine serum homocysteine levels and their relationships with
      inflammatory and atherothrombotic markers in psoriasis. Twenty patients with mild
      or moderate psoriasis and 20 age-matched healthy men were included in this study.
      Patients with acquired hyperhomocysteinaemia were excluded from both groups. The
      inflammation markers, mean platelet volume, C-reactive protein and ceruloplasmin
      levels, were significantly increased in the study group compared with the control
      group. In the study group there was decreased antithrombin III and total
      homocysteine levels, for haemostatic parameters. Folic acid levels,
      cardiovascular risk factors, endothelial inflammation markers and blood
      coagulation factors demonstrated significant correlations. Folic acid levels
      correlated inversely with homocysteine and positively with fibrinogen levels. In
      conclusion, increased homocysteine concentration and inflammation markers may
      play a role in the atherothrombotic state in psoriasis.

PMID- 18709302
TI  - Measurement of liver iron content by magnetic resonance imaging in 20 patients
      with overt porphyria cutanea tarda before phlebotomy therapy: a prospective
      study.
AB  - Liver iron content was evaluated by a magnetic resonance imaging-based method in
      20 consecutive patients with either sporadic or familial porphyria cutanea tarda.
      Serum ferritin, hepatitis C infection and the presence of the 2 main mutations of
      the hemochromatosis gene were also investigated. All patients showed good
      clinical response to phlebotomy. Initial liver iron content was normal (< 40
      micromol/g) in 9 cases, slightly increased (40-59 micromol/g) in 3 cases,
      moderately increased (60-99 micromol/g) in 6 cases or markedly increased (100-199
      micromol/g) in 2 cases). The ferritin level was raised (> 400 ng/ml) in 14/20
      patients and there was no obvious relationship with liver iron. Increased liver
      iron content was observed more frequently in patients with hemochromatosis
      mutation and less frequent in those with hepatitis C infection. Clinical response
      to phlebotomies was slightly better in patients with increased liver iron content
      even slightly, but patients with normal liver iron content also responded well,
      which suggests that iron depletion is an outstanding treatment independent of
      liver iron content. This study shows that increased liver iron content is not a
      constant finding in patients with porphyria cutanea tarda, especially in women,
      and that it is not a prerequisite for the efficiency of phlebotomy.

PMID- 18709303
TI  - Atrichia with papular lesions: a report of three novel human hairless gene
      mutations and a revision of diagnostic criteria.
AB  - Atrichia with papular lesions is a rare autosomal recessive condition
      characterized by complete irreversible hair loss during the first months of life
      and papules that appear during early childhood. Atrichia with papular lesions is
      frequently misdiagnosed as alopecia universalis, despite increasing reports of
      its prevalence and the presence of well-defined diagnostic criteria. Most cases
      of atrichia with papular lesions have been reported in consanguineous families
      residing in small geographical regions, but the increasing number of sporadic
      cases of unrelated individuals suggests that atrichia with papular lesions is
      more common than previously thought. Mutations in the human hairless gene on
      chromosome 8p12 have been implicated in this disease. Here, we report two novel
      heterozygous mutations in an Australian family and a novel homozygous mutation in
      2 Arab siblings. We also revise the diagnostic criteria for atrichia with papular
      lesions in order to clarify its uniqueness and distinguishing features from
      alopecia universalis.

PMID- 18709304
TI  - Febrile ulceronecrotic Mucha-Habermann disease: a case report and review of the
      literature.
AB  - Febrile ulceronecrotic Mucha-Habermann disease is a severe variant of pityriasis
      lichenoides et varioliformis acuta characterized by the sudden onset of
      ulceronecrotic skin lesions and associated with high fever and systemic symptoms.
      We report here a case of a 20-year-old woman in whom the disease started as
      pityriasis lichenoides et varioliformis acuta and evolved to febrile
      ulceronecrotic Mucha-Habermann disease. Almost 90% of the body surface was
      involved, together with high fever and malaise. Steroids alone proved to be an
      insufficient therapeutic procedure. The remission achieved was attributed to the
      use of methotrexate. To our knowledge, only 39 cases of febrile ulceronecrotic
      Mucha-Habermann disease have been reported in the literature to date.

PMID- 18709305
TI  - Patient's estimation of efficacy of various hyperhidrosis treatments in a
      dermatological clinic.
AB  - Hyperhidrosis is a common ailment, which is accompanied by a low quality of life.
      There are many current treatment options. The aims of this study were to
      investigate: (i) the characteristics of sweating in patients referred for
      hyperhidrosis; (ii) their quality of life, using the Dermatology Life Quality
      Index and the Hyperhidrosis Disease Severity Scale; and (iii) their estimation of
      efficacy of the treatments given, using a patient's global assessment score and
      the quality of life scores. In 47 of 94 patients (50%) responding to the
      questionnaires, hyperhidrosis was confined exclusively to the axillae. In 21
      (22%) of the patients, sweating in the axillae was combined with sweating of the
      hands and/or feet, face or other, more widespread, regions. Fifteen patients
      (16%) had generalized hyperhidrosis. In half of all cases, sweating occurred in
      attacks. Attacks were mostly triggered by warmth, exercise, emotions, or had no
      apparent cause. Quality of life was low in all cases. All treatments improved
      quality of life.

PMID- 18709306
TI  - Clinical manifestations and characteristics of patients with acute generalized
      exanthematous pustulosis in Asia.
AB  - Acute generalized exanthematous pustulosis is a rare, sterile inflammation of the
      skin (and mucous membranes) characterized by acute onset of generalized pustule
      formation, fever and leukocytosis, and a rapid resolution. A computer-based
      search of the literature revealed only a limited series of reports, none of them
      based on Asian patients. We identified and retrospectively analysed 16 biopsy
      proven and criteria-matched patients over a 15-year period in a single medical
      centre. The study showed a female predominance (11 of 16 patients), a relatively
      low association with systemic drugs (62.5% vs. 87% in a previous report) and
      normal renal function (in contrast to a previous report where 32% of patients had
      renal failure). The study also revealed high levels of C-reactive protein (76.0
      mg/l) and normal absolute eosinophil count (176.2/microl) in most patients.
      Furthermore, there was no difference between different treatment regimens regard
      ing the course and duration of the disease or the length of fever (p>0.05). In
      addition, if the patients were subdivided by aetiology into those strongly
      associated with or not strongly associated with systemic drugs, a significant
      difference was found in age of onset between the 2 groups (p<0.01).

PMID- 18709307
TI  - Cooling by frozen gel pack as pain relief during treatment of axillary
      hyperhidrosis with botulinum toxin a injections.
AB  - Botulinum toxin A injection is a well-described efficacious treatment for
      axillary hyperhidrosis. Although considered a safe treatment, many patients
      experience pain during injections. The purpose of the present study was to
      examine whether cooling by frozen gel packs applied in the axilla for 5 min
      before treatment could reduce pain. Thirty-six patients with axillary
      hyperhidrosis were included in this randomized, open-label prospective study, in
      which patients were their own controls. Pain was assessed before, during (four
      times), and immediately after treatment, using a numeric rating scale. The
      patients experienced statistically significant pain reduction, of 14-19%, in
      areas cooled by frozen gel pack (p<0.01). However, the clinical relevance of this
      relatively small pain reduction is questionable.

PMID- 18709308
TI  - Clinical follow-up of 102 anti-Ro/SSA-positive patients with dermatological
      manifestations.
AB  - Patients with Ro/SSA autoantibodies can develop cutaneous lupus erythematosus and
      photosensitivity. The aim of this study was to evaluate disease progression and
      clinical outcome in Ro/SSA-positive patients after 2 years in a prospectively
      followed cohort. A total of 102 previously clinically and serologically
      characterized Ro/SSA-positive patients received a questionnaire 2 years after the
      baseline investigation. Evaluation of 98 questionnaire responses was performed
      and clinical examination was offered to patients with cutaneous lupus
      erythematosus established at baseline, or skin symptoms developed over the 2 year
      period since baseline. Skin symptoms (42%) and arthralgia (31%) were common self
      reported health-related answers. Twenty of the 98 patients (20%) showed disease
      progression with development of new diagnoses such as drug-induced subacute
      cutaneous lupus erythematosus. This prospective study reveals that new autoimmune
      diseases and skin disease progress are common in Ro/SSA-positive patients also in
      the short-term perspective, and stresses the importance of regular follow-up of
      these patients.

PMID- 18709309
TI  - Targeted broadband ultraviolet b phototherapy produces similar responses to
      targeted narrowband ultraviolet B phototherapy for vitiligo: a randomized, double
      blind study.
AB  - Narrowband ultraviolet B (NB-UVB) phototherapy, with a 308-nm xenon chloride
      excimer laser, and targeted UVB phototherapy have produced encouraging
      therapeutic results for vitiligo. However, very few studies employing broadband
      UVB exist. Moreover, there has been no direct comparison study between broadband
      UVB and NB-UVB for the treatment of vitiligo. The aims of this study were to
      compare the repigmenting efficacy of targeted broadband UVB phototherapy with
      that of NB-UVB in an equi-erythemogenic manner. Twenty identical vitiliginous
      lesions from 10 patients were randomly allocated to receive either targeted
      broadband UVB or targeted NB-UVB phototherapy. UV fluences were started at 50% of
      the minimal erythema dose detected within the vitiliginous patches, then
      increased gradually, in the same manner, to ensure equi-erythemogenic comparison.
      Treatments were carried out twice weekly for 12 weeks. The results show that
      grade 1, i.e. 1-25% repigmentation, to grade 2, 26-50% repigmentation, occurred
      in 6 of 10 subjects. Responses in terms of repigmentation, de-pigmentation, or
      lack thereof, were similar between lesions receiving broadband and NB-UVB
      phototherapy. Onset of repigmentation occurred as early as 4 weeks of treatment
      in most subjects. Treatments were well tolerated, with only minimal erythema and
      hyperpigmentation. LIMITATIONS: The study was carried out in a small number of
      patients with skin types III, IV and V. The irradiation device was a targeted UVB
      device and thus the results may not be applicable to other light sources, such as
      the excimer laser or total-body irradiation cabinets. In conclusion, targeted
      broadband UVB produces similar clinical responses to targeted NB-UVB in the
      treatment of the non-segmental type of vitiligo.

PMID- 18709310
TI  - Segmentally arranged basaloid follicular hamartomas with osseous, dental and
      cerebral anomalies: a distinct syndrome.
AB  - A 39-year-old man presented with multiple basaloid follicular hamartomas
      involving the right side of his body in a systematized pattern following
      Blaschko's lines. His right leg was 22.5 cm shorter than the left, and
      rudimentary pre-axial polydactyly was noted on the left hand and the right foot.
      The teeth of the right maxilla were hypoplastic. DNA analysis of blood
      lymphocytes and fibroblasts from lesional skin did not reveal any mutation in the
      Patched gene. On account of this case and of 8 similar cases found in th e
      literature, the spectrum of a distinct syndrome is delineated. Ipsilateral
      extracutaneous defects include cervical ribs, polydactyly, malformed thumb and
      disproportionate overgrowth or deficient growth of limb bones; dental anomalies
      in the form of anodontia, hypodontia or ameloblastoma; and cerebral defects such
      as mental retardation, unsteady gait, meningioma and optic glioma. The cutaneous
      lesions of this syndrome should not be called "basal cell naevus" as this will
      lead to continuing confusion with Gorlin syndrome. The molecular basis of the
      disorder remains to be elucidated.

PMID- 18709311
TI  - Punch-grafting to enhance healing and to reduce pain in complicated leg and foot
      ulcers.

PMID- 18709312
TI  - Interaction of human papillomavirus DNA with factor XIIIa-positive dermal
      dendrocytes in vulvar lesions.

PMID- 18709313
TI  - Bullous dermatomyositis: a marker of poor prognosis and aggressive internal
      malignancy?

PMID- 18709314
TI  - Spontaneous regression of generalized angiolymphoid hyperplasia with eosinophilia
      in a 2-year-old boy.

PMID- 18709315
TI  - Vogt-koyanagi-harada syndrome associated with psoriasis and autoimmune thyroid
      disease.

PMID- 18709316
TI  - Diagnosis of Hailey-Hailey disease facilitated by DNA testing: a novel mutation
      in ATP2C1.

PMID- 18709317
TI  - Bullous pemphigoid of the perineum and perianal area: a rare localized form in
      adults.

PMID- 18709318
TI  - Coexistence of diffuse reactive angioendotheliomatosis and neutrophilic
      dermatosis heralding primary antiphospholipid syndrome.

PMID- 18709319
TI  - Successful treatment of an elderly patient with refractory ultraviolet-A
      sensitive atopic eczema with mycophenolic acid.

PMID- 18709320
TI  - Keratitis-ichthyosis-deafness syndrome lacking subjective hearing impairment.

PMID- 18709321
TI  - Traumatized recurrent melanocytic naevus with typical starburst pattern on
      dermoscopy.

PMID- 18709322
TI  - Paraneoplastic pemphigus developed shortly after resection of follicular
      dendritic cell sarcoma.

PMID- 18709323
TI  - Blue naevus with pigment network-like structure on dermoscopy.

PMID- 18709324
TI  - Photosensitive psoriasis vulgaris inducible by a single suberythematous dose of
      ultraviolet B irradiation.

PMID- 18709325
TI  - Staphylococcal scalded skin syndrome as a harbinger of late-onset staphylococcal
      septicaemia in a premature infant of very low birth weight.

PMID- 18709326
TI  - Psoriasis vulgaris associated with acne vulgaris: differential effects of
      biologicals?

PMID- 18709327
TI  - Beneficial and rapid effect of infliximab on the course of toxic epidermal
      necrolysis.

PMID- 18709328
TI  - Primary cutaneous epithelioid angiosarcoma.

PMID- 18709329
TI  - A BHD germline mutation identified in an Asian family with Birt-Hogg-Dube
      syndrome.

PMID- 18709330
TI  - Pseudoporphyria or porphyria cutanea tarda? Diagnostic and treatment
      difficulties.

PMID- 18709331
TI  - Skin nodules in rheumatoid arthritis due to infection with Mycobacterium
      haemophilum.

PMID- 18709332
TI  - Heavy metals in fish from lakes in Latvia: concentrations and trends of changes.
AB  - The purpose of this study was to evaluate the level of heavy metal contamination
      of perch (Perca fluviatilis) from inland waters in Latvia. The level of metal
      (Cd, Cu, Co, Pb, Ni, Mn, Zn, Fe) accumulation in fish tissues (muscle, liver, and
      gills) relative to contamination level, gender, age, and tissue type were studied
      in fish samples from 14 bog (dystrophic) lakes and 23 lakes of different trophic
      status. Samples from some sites in the vicinity of the largest cities had
      significantly increased metal levels. In contrast, fish tissues from bog lakes
      had very low metal levels, possibly because of the high concentrations of natural
      organic matter in these waters.

PMID- 18709333
TI  - Automated amino acid side-chain NMR assignment of proteins using (13)C- and (15)N
      resolved 3D [ (1)H, (1)H]-NOESY.
AB  - ASCAN is a new algorithm for automatic sequence-specific NMR assignment of amino
      acid side-chains in proteins, which uses as input the primary structure of the
      protein, chemical shift lists of (1)H(N), (15)N, (13)C(alpha), (13)C(beta) and
      possibly (1)H(alpha) from the previous polypeptide backbone assignment, and one
      or several 3D (13)C- or (15)N-resolved [(1)H,(1)H]-NOESY spectra. ASCAN has also
      been laid out for the use of TOCSY-type data sets as supplementary input. The
      program assigns new resonances based on comparison of the NMR signals expected
      from the chemical structure with the experimentally observed NOESY peak patterns.
      The core parts of the algorithm are a procedure for generating expected peak
      positions, which is based on variable combinations of assigned and unassigned
      resonances that arise for the different amino acid types during the assignment
      procedure, and a corresponding set of acceptance criteria for assignments based
      on the NMR experiments used. Expected patterns of NOESY cross peaks involving
      unassigned resonances are generated using the list of previously assigned
      resonances, and tentative chemical shift values for the unassigned signals taken
      from the BMRB statistics for globular proteins. Use of this approach with the 101
      amino acid residue protein FimD(25-125) resulted in 84% of the hydrogen atoms and
      their covalently bound heavy atoms being assigned with a correctness rate of 90%.
      Use of these side-chain assignments as input for automated NOE assignment and
      structure calculation with the ATNOS/CANDID/DYANA program suite yielded structure
      bundles of comparable quality, in terms of precision and accuracy of the atomic
      coordinates, as those of a reference structure determined with interactive
      assignment procedures. A rationale for the high quality of the ASCAN-based
      structure determination results from an analysis of the distribution of the
      assigned side chains, which revealed near-complete assignments in the core of the
      protein, with most of the incompletely assigned residues located at or near the
      protein surface.

PMID- 18709334
TI  - MMP-13 is over-expressed in renal cell carcinoma bone metastasis and is induced
      by TGF-beta1.
AB  - Bone metastasis occurs frequently in renal cell carcinoma (RCC) patients causing
      significant morbidity by stimulating excessive osteolysis, yet the mechanisms
      responsible have been little studied. Matrix metalloproteinases (MMPs) are over
      expressed in many cancer types and are believed to play a role in bone
      metastasis, however, the expression of MMPs in RCC bone metastasis (RBM) has not
      been investigated. Due to their ability to degrade the main component of organic
      bone matrix, type I collagen, we investigated the expression of MMP-1, -2, -8, 
      9, and -13 in RBM. By quantitative (q)RT-PCR, expression of MMP-13 was
      significantly increased in RBM tissues relative to that in RCC and adjacent
      normal kidney while no differences in the expression of MMP-1, -2, -8, or -9 mRNA
      were observed. Correspondingly, increased expression of MMP-13 protein was also
      observed in RBM relative to RCC by immunohistochemical analysis. Intriguingly,
      the expression of MMP-13 in the human RBM cell line RBM1-IT4 was stimulated by
      TGF-beta1, a growth factor abundant in the bone microenvironment and known to
      promote RBM-induced osteolysis in animals. Exposure of RBM1-IT4 cells to TGF
      beta1 increased MMP-13 mRNA levels as well as the latent and active forms of MMP
      13 protein. Further, stable expression of a dominant-negative TGF-beta type II
      receptor in RBM1-IT4 cells inhibited MMP-13 expression following TGF-beta1
      exposure. These data suggest that MMP-13 expression is elevated in RBM relative
      to primary RCC and adjacent normal kidney, and is regulated at the cellular level
      by TGF-beta1.

PMID- 18709335
TI  - Construction of a high-performance human fetal liver-derived lentiviral cDNA
      library.
AB  - The gene transduction method is a very powerful tool, not only in basic science
      but also in clinical medicine. Regenerative medicine is one field that has close
      connection with both basic and clinical. Recently, it has been reported that
      induced pluripotent stem (iPS) cells can be produced from somatic cells by a
      three or four gene transduction. We have also recently reported that lentiviral
      gene transfer of the tal1/scl gene can efficiently differentiate non-human
      primate common marmoset ES cells into hematopoietic cells without the support of
      stromal cells. In this study, we constructed a high-performance human fetal liver
      derived lentiviral expression library, which contains a high number of individual
      clones, in order to develop a very helpful tool for understanding early
      hematopoiesis and/or hepatocytosis for future regenerative medicine. Our
      lentiviral cDNA library consisted of more than 8 x 10(7) individual clones, and
      their average insert size was >2 kb. DNA sequence analysis for each individual
      inserted cDNAs revealed that >60% contained the full-length protein-coding
      regions for many genes including cytokine receptors, cytoplasmic proteins,
      protein inhibitors, and nuclear factors. The transduction efficiency on 293T
      cells was 100% and the average size of an integrated cDNA was ~1.1 kb. These
      results suggest that our lentiviral human fetal liver cDNA expression library
      could be a very helpful tool for accelerating the discovery of novel genes that
      are involved in early hematopoiesis and hepatopoiesis and to make the use of iPS
      cells more efficient in the field of regenerative medicine.

PMID- 18709336
TI  - Oxidative stress induced by lead in chloroplast of spinach.
AB  - Seedlings of spinach were grown in Hoagland's medium containing 0, 20, 40, 60,
      80, 100 microM PbCl2, respectively, for 4 weeks. Chloroplasts were assayed for
      overproduction of reactive oxygen species (ROS) such as superoxide radicals (O2(*
      )) and hydrogen peoxide (H2O2) and of lipid peroxide (malonyldialdehyde) and for
      activities of the antioxidant enzymes such as superoxide dismutase, catalase,
      ascorbate peroxidase, and guaiacol peroxidase and glutathione content, oxygen
      evolving rate, and chlorophyll content. Increase in both ROS and lipid peroxide
      content and reduction in photosynthesis and activities of the antioxidant defense
      system indicated that spinach chloroplast underwent a stress condition due to an
      oxidative attack. Seedling growth cultivated in containing Pb2+ media was
      significantly inhibited. The results imply that spinach chloroplast was not able
      to tolerate the oxidative stress induced by Pb2+ due to having no effective
      antioxidant defense mechanism.

PMID- 18709337
TI  - Attenuation of Zn-induced acute pancreatitis in Wistar rat fed on Cu- and Mg-
      enriched modified poultry egg Psi.
AB  - Zinc (Zn) consumption has increased in many populations either due to the
      increased intake of Zn-fortified foods as in the USA or in agricultural food
      stuffs as in some Indian states during the last decade. Its excessive intake has
      been reported to induce acute pancreatitis (AP) in many studies due to increase
      in oxidative stress that was further reported to cause Cu and Mg deficiencies.
      This led us to design a modified poultry egg (ME(Psi)) enriched with Cu and Mg
      along with other antioxidants, and its efficacy on Zn-induced AP was studied in
      male Wistar rats. In one set, the rats were fed on equacaloric semi-synthetic
      basal diet containing 20 mg Zn/kg diet (control, group I), and Zn-induced AP-I
      diet and AP-II diet containing 40 and 80 mg Zn/kg diet (groups II and III) for
      180 days, respectively. In another set, the rats were initially fed on Zn-induced
      AP-I and AP-II diets for 90 days and then shifted to ME(Psi)-mixed Zn-induced AP
      I and AP-II diets in groups IIME and IIIME for another 90 days. At the end of the
      experiment, data displayed increased serum and urinary Zn, Cu, and Mg levels in
      groups II and III rats, which were reduced and approached closer to control group
      I after ME(Psi) feeding in groups IIME and IIIME rats. Transmission electron
      microscopic studies of acinar cells revealed progressive dilation,
      vesicularization, and degeneration of endoplasmic reticulum (ER), and decrease in
      zymogen granules (ZG) in groups II and III rats in contrast to their curvilinear
      or concentric long parallel running cisternal profile of ER in control group I.
      The treatment of ME(Psi) helped in the restoration of the ER profile and ZG
      number, approaching closer to the control group I. The degree of recovery was
      dependent upon the degree of toxicity caused by the amount of Zn given in the
      diet. The results of this study suggest that ME(Psi)-mixed diet can protect the
      acinar cells from the deleterious effects of Zn by decreasing the oxidative
      stress.

PMID- 18709338
TI  - Clinical and analytical toxicology of dietary supplements: a case study and a
      review of the literature.
AB  - The use of dietary supplements has grown dramatically in the last decade. A large
      number of dietary and herbal supplements escape regulatory and quality control;
      components of these preparations are poisonous and may contain, among other
      toxins, heavy metals. Uncontrolled use of dietary and herbal supplements by
      special populations, such as the military, may therefore pose a health risk.
      Clinical symptoms are not always properly attributed to dietary supplements;
      patients often do not mention supplement use to their health care provider.
      Therefore, a health risk estimate is hard to make on either the individual or the
      population level. The literature on this issue was reviewed and discussed in the
      light of a representative clinical-chemical case study. This case study was
      performed on a host of preparations that were used by one single individual in
      the military. Both essential (chromium, copper, zinc, and iron) and poisonous
      (arsenic, lead, and nickel) trace elements were determined using inductively
      coupled plasma combined with optical emission spectrometry (ICP-OES) or with mass
      spectrometry (ICP-MS). Arsenic and lead were detected at exposure levels
      associated with health risks. These health risks were detected predominantly in
      hormone-containing supplements and the herbs and botanicals used for performance
      enhancement. To the extent that this is a representative sample, there is an
      underestimation of supplement use and supplement risk in the US military, if not
      in the general population. Since clinical symptoms may be attributed to other
      causes and, unless patients are specifically asked, health care providers may not
      be aware of their patients' use of dietary supplements, a strong support of
      laboratory diagnostics, such as a toxicological screening of blood or urine, is
      required. In addition, screening of the preparations themselves may be advised.

PMID- 18709341
TI  - [Fatalities due to nitrous oxide. Complications from mistakes in nitrous oxide
      supply].
AB  - Despite inspiratory oxygen fraction measurement being regulated by law in the
      European norm EN 740, fatal errors in nitrous oxide delivery still occur more
      frequently than expected, especially after construction or repair of gas
      connection tubes. Therefore, if nitrous oxide is to be used further in a
      hospital, all technical measures and system procedures should be employed to
      avoid future catastrophes. Among these are measurement of the inspiratory oxygen
      fraction (F(I)O(2)) and an automatic limitation of nitrous oxide. Also all
      anaesthetists involved should be informed about repair or construction of central
      gas supply tubes. Additionally, more awareness of this problem in daily routine
      is necessary. Furthermore, a system of detecting and analysing errors in
      anaesthesia has to be improved in each hospital as well as in the anaesthesia
      community as a whole. Measures for a better "error culture" could include data
      exchange between different critical incident reporting systems, analysis of
      closed claims, and integration of medical experts in examination of recent
      catastrophes.

PMID- 18709342
TI  - [Chronic hand eczema: epidemiology and therapeutic evidence].
AB  - Hand eczema (HE) is one of the most frequent skin diseases, although it is not a
      homogenous entity. The degree of severity can range from mild manifestations to
      severe chronic cases which are refractory to therapy and tend to disable
      patients. Chronic HE is a high social and economic impact and often leads to a
      loss in quality of life. Although there are many options, the therapy of chronic
      HE is difficult and often unsuccessful. Randomized controlled clinical trials
      demonstrating the efficacy of therapeutic options, including established ones,
      are lacking.

PMID- 18709343
TI  - Oligomeric and fibrillar species of beta-amyloid (A beta 42) both impair
      mitochondrial function in P301L tau transgenic mice.
AB  - We recently provided evidence for a mitochondrial dysfunction in P301L tau
      transgenic mice, a strain modeling the tau pathology of Alzheimer's disease (AD)
      and frontotemporal dementia (FTD). In addition to tau aggregates, the AD brain is
      further characterized by A beta peptide-containing plaques. When we addressed the
      role of A beta, this indicated a synergistic action of tau and A beta pathology
      on the mitochondria. In the present study, we compared the toxicity of different
      A beta 42 conformations in light of recent studies suggesting that oligomeric
      rather than fibrillar A beta might be the actual toxic species. Interestingly,
      both oligomeric and fibrillar, but not disaggregated (mainly monomeric) A beta 42
      caused a decreased mitochondrial membrane potential in cortical brain cells
      obtained from FTD P301L tau transgenic mice. This was not observed with
      cerebellar preparations indicating selective vulnerability of cortical neurons.
      Furthermore, we found reductions in state 3 respiration, the respiratory control
      ratio, and uncoupled respiration when incubating P301L tau mitochondria either
      with oligomeric or fibrillar preparations of A beta 42. Finally, we found that
      aging specifically increased the sensitivity of mitochondria to oligomeric A beta
      42 damage indicating that oligomeric and fibrillar A beta 42 are both toxic, but
      exert different degrees of toxicity.

PMID- 18709344
TI  - [Neonatal traumatic epiphyseolysis of the humeral head. A rare occurrence].
AB  - Neonatal traumatic epiphyseolysis of the humeral head is rare, and only a few
      cases are reported in the literature. We present a case of a 13-day-old female
      newborn with malposition and relaxation of the left upper limb. The clinical
      examination showed distinct range of motion particularly for abduction. Magnetic
      resonance imaging (MRI) indicated epiphyseolysis of the humeral head. Closed
      reposition followed by immobilisation was done. The following MRI showed correct
      axis with adaption of the humeral head. Later, malposition of the axis with
      angulation in the ventromedial position was seen. This status was not followed by
      renewed repositioning. The x-ray examination 5 months later and MRI 9 months
      later showed a centered position of the epiphysis. In conclusion, neonatal
      traumatic epiphyseolysis of the proximal humeral head occurs rarely but should be
      considered, particularly with unclear relaxation of the limb.

PMID- 18709345
TI  - [The Will Rogers phenomenon and its impact on imaging diagnostics].
AB  - The Will Rogers phenomenon is a possible cause of systematic distortions in the
      results of clinical studies, which can be produced if stage migration occurs
      during a disease. The term refers to the apparent paradox which is observed when
      an element is changed from one set to another and the average values of both sets
      are altered in the same way. The effect is due to the prerequisite that the
      numerical value of the element being moved is placed between the mean values of
      both groups. In medicine, this phenomenon is a consequence of the evolution of
      staging procedures and may be source of misleading statistics for survival in
      cancer. Both advanced pathological assessment and modern imaging techniques may
      be involved. The wrong conclusions are induced by comparing the effects of
      treatment in contemporary patient groups, which profit from extensive diagnostic
      procedures, to those of historical controls. Treatise informs about the history
      of the term and illustrates its effects by numerical examples and clinical data.
      Finally, a model computation based on current PET/CT figures is offered.

PMID- 18709346
TI  - [Therapy-induced effects in normal tissue].
AB  - More than 50% of cancer patients survive for more than 5 years, owing to modern
      and effective treatment. Therefore, long-term sequelae of treatment are more
      frequently seen than in the past. Such effects on normal tissue may both mimic
      and obscure tumor recurrences. Besides the direct consequences of surgery, tissue
      damage due to radiation or chemotherapy frequently cause problems in differential
      diagnosis. Among the numerous sequelae of radiotherapy, the most prominent are
      disturbance of the blood-brain barrier, radiation pneumonitis, osteodystrophy and
      osteoradionecrosis, fatty changes of bone marrow, or increased radiodensity of
      breast parenchyma. Chemotherapy may cause, e.g., diffuse abnormalities of white
      matter, pneumonitis and lung fibrosis, cardiomyopathy, or diffuse and patchy
      changes in bone marrow signals in MRI. The most devastating long-term
      complications are secondary cancers and leukemia induced by both radiotherapy and
      chemotherapy.

PMID- 18709347
TI  - [Cystic tumors of the pancreas].
AB  - Cystic lesions of the pancreas encompass a broad spectrum of benign,
      premalignant, and malignant tumors which are primarily cystic or result from
      cystic necroses of solid neoplasms. Because of the wide use of cross-sectional
      imaging techniques they are increasingly being identified in asymptomatic
      patients as well as in patients presenting with abdominal pain, jaundice or
      pancreatitis. Among these lesions, intraductal papillary mucinous neoplasms,
      serous cystic neoplasms and mucinous cystic neoplasms represent the majority of
      cases. With increasing experience with these tumors, a refinement of our
      understanding of their morphology and of their natural course has emerged. It is
      important to be familiar with the CT and MR imaging features of these lesions to
      differentiate these tumors and to orient the diagnosis towards benign or
      malignant forms. Because characterization of cystic tumors of the pancreas can
      sometimes be difficult due to overlapping imaging features, additional criteria
      such as clinical symptoms, localization, age and gender have to be taken into
      account. If appropriately treated, these tumors can usually be cured by resection
      and the decreasing risk of pancreatic surgery has led to an increasing number of
      resections of pancreatic tumors. The management of cystic tumors of the pancreas
      has not yet been standardized and the correct evaluation and subsequent
      management of the disease in asymptomatic patients have not been fully defined.

PMID- 18709350
TI  - [TESE and mTESE. Therapeutic options in male infertility due to testicular
      azoospermia].
AB  - Modern techniques of testicular sperm extraction (TESE) make it possible for an
      infertile man to father a child. The operations are standardized to a large
      extent and the underlying morphological alterations of spermatogenesis also
      appear to be sufficiently known. Current research is focused on prognostic
      factors for the testicular material that determine the sperm retrieval rate and
      success rates after in vitro fertilization/intracytoplasmic sperm injection (IVF
      ICSI).TESE and microTESE are accepted standard operations for testicular sperm
      retrieval for IVF/ICSI. Predictions for effective sperm recovery are addressed.

PMID- 18709351
TI  - [Minimally invasive percutaneous nephrolitholapaxy (MIP)].
AB  - Minimally invasive percutaneous nephrolithopaxy (MIP) was developed to combine
      the excellent stone-free rates of the conventional percutaneous nephrolithopaxy
      (PCNL) technique with the low morbidity of the miniaturized PCNL (Mini-Perc) and,
      at the same time, achieve a high level of patient comfort. The procedure is
      characterized not only by the diameter of the miniaturized 18-Fr Amplatz sheath
      that was adopted from the Mini-Perc but also by the following features:
      ultrasound-guided puncture of the kidney; single-step dilatation of the access
      tract; ballistic lithotripsy; a low-pressure irrigation system together with
      stone retraction by irrigation with a specially designed nephroscope sheath, for
      the so-called vacuum cleaner effect; and a sealed and tubeless access tract with
      primary closure of the channel independent of hemorrhage and without a second
      look procedure.The results of the first 57 patients demonstrate primary stone
      free rates of 92.9% with operating times averaging 62 (25-123) min. Severe
      complications, such as sepsis or bleeding requiring blood transfusion, did not
      occur. The high and predictable stone-free rate and a low morbidity comparable to
      that of ureteroscopy and extracorporeal shock-wave lithotripsy make MIP an
      attractive option for patients and urologists. The "vacuum cleaner effect" with
      quick removal of stone fragments reduces operating time and prevents new stone
      formation by avoiding residual fragments. The direct and primary closure of the
      access tract increases patient comfort and is justified by the reintervention
      rate of less than 8% in the presented cohort.The lack of a need for second-look
      nephroscopies, the vacuum cleaner effect, improved patient comfort without
      nephrostomy tubes, as well as surgery times comparable to that of traditional
      PCNL demonstrate a consequent evolution of the Mini-Perc. MIP therefore
      represents a promising and future-oriented module in modern stone therapy.

PMID- 18709352
TI  - Effects of acute insulin-induced hypoglycaemia on psychomotor function: people
      with type 1 diabetes are less affected than non-diabetic adults.
AB  - AIMS/HYPOTHESIS: We examined the effects of acute insulin-induced hypoglycaemia
      on psychomotor function in non-diabetic volunteers and in adults with type 1
      diabetes. METHODS: Non-diabetic adults (n = 20) and adults with type 1 diabetes
      mellitus (n = 16) each underwent a euglycaemic-hyperinsulinaemic glucose clamp on
      two separate occasions. Arterialised blood glucose was maintained for 1 h at
      either 4.5 mmol/l (euglycaemia) or 2.5 mmol/l (hypoglycaemia). During this time
      participants underwent neuropsychological tests to assess psychomotor function.
      RESULTS: During hypoglycaemia the non-diabetic participants showed a significant
      deterioration in the following: (1) four-choice reaction time (p = 0.008); (2)
      grooved pegboard (a test of manual dexterity; p = 0.004); (3) hand steadiness (p
      = 0.003); (4) pursuit rotor (a test of fine motor function, attention and
      coordination; p = 0.018); and (5) test of total body coordination (p = 0.004). No
      significant differences were observed between euglycaemia and hypoglycaemia in
      hand-grip (p = 0.897) and line tracing time (p = 0.480) tests. In type 1 diabetes
      mellitus patients, only four-choice reaction time (p = 0.023) and pursuit rotor
      (p = 0.045) were impaired significantly during hypoglycaemia.
      CONCLUSIONS/INTERPRETATION: Although acute hypoglycaemia caused significant
      impairment of several psychomotor functions in non-diabetic adults, a lower
      magnitude of impairment was observed in those with type 1 diabetes. The mechanism
      underlying this discrepant effect of hypoglycaemia on psychomotor function
      remains unknown, but may be related to the difference in sympathoadrenal
      activation observed between the groups. People with type 1 diabetes may also have
      had a behavioural advantage of over non-diabetic participants derived from their
      previous exposure to hypoglycaemia or potentially the disparate results arose
      from hypoglycaemia-induced cerebral adaptation.

PMID- 18709353
TI  - Intravenous AICAR administration reduces hepatic glucose output and inhibits
      whole body lipolysis in type 2 diabetic patients.
AB  - AIMS/HYPOTHESIS: The 5'-AMP-activated protein kinase (AMPK) pathway is intact in
      type 2 diabetic patients and is seen as a target for diabetes treatment. In this
      study, we aimed to assess the impact of the AMPK activator 5-aminoimidazole-4
      carboxamide riboside (AICAR) on both glucose and fatty acid metabolism in vivo in
      type 2 diabetic patients. METHODS: Stable isotope methodology and blood and
      muscle biopsy sampling were applied to assess blood glucose and fatty acid
      kinetics following continuous i.v. infusion of AICAR (0.75 mg kg(-1) min(-1))
      and/or NaCl (0.9%) in ten male type 2 diabetic patients (age 64 +/- 2 years; BMI
      28 +/- 1 kg/m(2)). RESULTS: Plasma glucose rate of appearance (R (a)) was reduced
      following AICAR administration, while plasma glucose rate of disappearance (R
      (d)) was similar in the AICAR and control test. Consequently, blood glucose
      disposal (R (d) expressed as a percentage of R (a)) was increased following AICAR
      infusion (p < 0.001). Accordingly, a greater decline in plasma glucose
      concentration was observed following AICAR infusion (p < 0.001). Plasma NEFA R
      (a) and R (d) were both significantly reduced in response to AICAR infusion, and
      were accompanied by a significant decline in plasma NEFA concentration. Although
      AMPK phosphorylation in skeletal muscle was not increased, we observed a
      significant increase in acetyl-CoA carboxylase phosphorylation (p < 0.001).
      CONCLUSIONS/INTERPRETATION: The i.v. administration of AICAR reduces hepatic
      glucose output, thereby lowering blood glucose concentrations in vivo in type 2
      diabetic patients. Furthermore, AICAR administration stimulates hepatic fatty
      acid oxidation and/or inhibits whole body lipolysis, thereby reducing plasma NEFA
      concentration.

PMID- 18709354
TI  - Respiratory, metabolic and hemodynamic effects of clonidine in ventilated
      patients presenting with withdrawal syndrome.
AB  - OBJECTIVE: To investigate the respiratory, metabolic and hemodynamic effects of
      clonidine in ventilated patients presenting with withdrawal syndrome after
      sedation interruption. DESIGN: Prospective, interventional, single-center study
      in 30 ventilated ICU patients. INTERVENTIONS: Metabolic [oxygen consumption
      (VO(2)), CO(2) production (VCO(2)), resting energy expenditure (REE)],
      respiratory [minute ventilation (V (E)), tidal volume (V (T)), respiratory rate
      (RR)] and hemodynamic (HR, SAP, MAP) parameters were measured in 30 ventilated
      ICU patients. Measurements were performed first under sedation with remifentanil
      propofol, then after sedation interruption, and finally after clonidine
      administration (0.9-1.8 mg of clonidine in two doses of 10 min interval).
      RESULTS: Sedation interruption produced significant increases in the hemodynamic
      parameters (SAP and MAP by 33%, HR by 37%), and metabolic rate (increase in VO(2)
      by 70%, VCO(2) by 88% and REE by 74%), leading to high respiratory demands
      (increase in V (E) from 9 to 15 l/min). The V (E) was increased due to a twofold
      increase in the RR; V (T) remained constant. In 25 out of 30 patients, clonidine
      administration decreased the hemodynamic (SAP, MAP and HR), metabolic (VO(2),
      VCO(2), REE) and respiratory parameters to values close to those observed with
      sedation. Clonidine induced mild sedation and patients became more cooperative
      with the ventilator. All patients responding to clonidine were weaned from the
      ventilator in 2 days (median, range 1-18 days). CONCLUSION: Patients with
      withdrawal syndrome had significantly elevated hemodynamic, metabolic and
      respiratory demands. Clonidine significantly decreased these demands, induced
      mild sedation and facilitated patient cooperation with the ventilator, enabling
      ventilator weaning.

PMID- 18709355
TI  - Isolation and characterization of porins from Desulfovibrio piger and Bilophila
      wadsworthia: structure and gene sequencing.
AB  - The outer membrane proteins of Desulfovibrio piger and Bilophila wadsworthia (Omp
      DP and Omp-BW, respectively) and the genes encoding them (omp-DP and omp-BW) were
      isolated and characterized. Native Omp-DP and Omp-BW form a trimeric structure of
      approximately 120 kDa. These proteins disaggregated into monomers with a
      molecular weight of approximately 53 kDa after heating at 95 degrees C for 10
      min. The pore-forming abilities of these oligomeric proteins demonstrated that
      they form small nonspecific channels with an exclusion limit of 260-300 Da. The
      omp-DP and omp-BW genes were cloned and sequenced. Sequence analyses revealed an
      open reading frame of 1,512 bp for omp-DP and 1,440 bp for omp-BW. The mature Omp
      DP protein consisted of 480 amino acids and had a calculated MW of 53,290 Da. The
      mature Omp-BW protein consisted of 456 amino acids and had a calculated MW of
      50.050 Da. Alignment of Omp-DP with Omp-BW revealed 54% homology, whereas
      alignment with other known porins showed a low level of homology. Analysis of the
      secondary structures indicated that both proteins span the outer membrane 18
      times with amphipathic beta-strands. This research presents porins which were
      isolated and characterized for the first time from bacteria belonging to the
      Desulfovibrionaceae family.

PMID- 18709356
TI  - Active extracts of wild fruiting bodies of Antrodia camphorata (EEAC) induce
      leukemia HL 60 cells apoptosis partially through histone hypoacetylation and
      synergistically promote anticancer effect of trichostatin A.
AB  - The endemic species of Antrodia camphorate (AC) is a promising chemotherapeutic
      drug for cancer. We found that the ethanol extract from wild fruiting bodies of
      Antrodia camphorata (EEAC) could induce HL 60 cells apoptosis via histone
      hypoacetylation, up-regulation of histone deacetyltransferase 1 (HDAC 1), and
      down-regulation of histone acetyltransferase activities including GCN 5, CBP and
      PCAF in dose-dependent manner. In combination with histone deacetylase inhibitor,
      trichostatin A (TSA), did not block EEAC-induced apoptosis. Interestingly,
      combined treatment (100 nM of TSA and 100 microg/ml EEAC) caused synergistic
      inhibition of cell growth and increase of apoptotic induction. EEAC could
      effectively increase the cytotoxic sensitivity of TSA through the up-regulation
      of DR5 and NFkappaB activation. In this present study, bioassay-guided
      fractionation of EEAC led to a major active compound, zhankuic acid A, as the
      bioactive marker. Moreover, our findings may represent an experimental basis for
      developing EEAC as a potential chemotherapeutic adjuvant.

PMID- 18709357
TI  - Chronic treatment and withdrawal of the cannabinoid agonist WIN 55,212-2 modulate
      the sensitivity of presynaptic receptors involved in the regulation of monoamine
      syntheses in rat brain.
AB  - Brain monoamines are involved in many neurochemical and behavioral effects of
      cannabinoids, but little is known on the regulation of noradrenaline, dopamine,
      and serotonin (5-HT) synthesis in cannabinoid addiction. This study investigated
      in rat brain the chronic effects of the potent cannabinoid agonist WIN 55,212-2
      and of rimonabant-precipitated withdrawal, as well as the sensitivity of
      synthesis-modulating inhibitory receptors, on the accumulation of L-3,4
      dihydroxyphenylalanine (DOPA) and 5-HTP after decarboxylase inhibition. Acute WIN
      (8 mg/kg; 1 h) increased DOPA synthesis in cortex (52%), hippocampus (51%), and
      cerebellum (56%) and decreased DOPA accumulation in striatum (31%). Acute WIN
      also decreased the synthesis of 5-HTP in all brain regions (40-53%). Chronic WIN
      (2-8 mg/kg; 5 days) and/or antagonist-precipitated withdrawal induced tolerance
      to the acute effects of WIN on the accumulation of DOPA (cortex and striatum) and
      5-HTP (all brain regions). The inhibitory effect of clonidine (alpha2-agonist; 1
      mg/kg) on the accumulation of DOPA (15-41%) and 5-HTP (22-41%) was markedly
      decreased or abolished after chronic WIN and precipitated withdrawal, mainly in
      noradrenergic and serotonergic brain regions, which indicated desensitization of
      alpha2-autoreceptors and alpha2-heteroreceptors regulating the synthesis of
      noradrenaline and 5-HT. In WIN-dependent rats (chronic and withdrawal states),
      the effect of a low dose of (+/-)-8-hydroxy-2-(di-n-propylamino)-tetralin (5-HT1A
      agonist; 0.1 mg/kg) on the accumulation of precursor amino acids was markedly
      potentiated in cerebellum and striatum, indicating the induction of
      supersensitivity of 5-HT1A-autoreceptors and 5-HT1A-heteroreceptors that regulate
      the synthesis of 5-HT, noradrenaline, and dopamine in these brain regions. These
      chronic adaptations in presynaptic receptor function could play a relevant role
      in cannabinoid addiction.

PMID- 18709358
TI  - Procognitive and antipsychotic efficacy of glycine transport 1 inhibitors (GlyT1)
      in acute and neurodevelopmental models of schizophrenia: latent inhibition
      studies in the rat.
AB  - RATIONALE: SSR103800 and SSR504734 are novel glycine transport 1 (GlyT1)
      inhibitors with therapeutic potential for the treatment of schizophrenia.
      OBJECTIVE: The present studies investigated the effects of GlyT1 inhibitors in
      acute pharmacological and neurodevelopmental models of schizophrenia using latent
      inhibition in the rat; these latent inhibition (LI) models are believed to be
      predictive for treatments of positive, negative, and cognitive aspects of
      schizophrenia. MATERIALS AND METHODS: LI, the poorer conditioning to a previously
      irrelevant stimulus, was measured in a conditioned emotional response procedure
      in male rats. The effects of SSR103800 or SSR504734 (both at 1, 3, and 10 mg/kg,
      i.p.) were determined on amphetamine-induced disrupted LI, MK-801-induced
      abnormally persistent LI, and neurodevelopmentally induced abnormally persistent
      LI in adult animals that had been neonatally treated with a nitric oxide synthase
      inhibitor. RESULTS: SSR103800 (1 and 3 mg/kg) and SSR504734 (1 and 10 mg/kg)
      potentiated LI under conditions where LI was not present in nontreated controls
      and SSR103800 (1 mg/kg) reversed amphetamine-induced disrupted LI while not
      affecting LI on its own. Additionally, SSR103800 (1 and 3 mg/kg) and SSR504734 (3
      and 10 mg/kg) reversed abnormally persistent LI induced by MK-801. In the
      neurodevelopmental model, SSR504734 (3 and 10 mg/kg) reverted the LI back to
      control (normal) levels. CONCLUSIONS: These preclinical data, from acute and
      neurodevelopmental models, suggest that GlyT1 inhibition may exhibit activity in
      the positive, negative, and cognitive symptom domains of schizophrenia.

PMID- 18709361
TI  - The genetically modified foods debate: demystifying the controversy through
      analytical chemistry.

PMID- 18709359
TI  - Selective phosphodiesterase inhibitors: a promising target for cognition
      enhancement.
AB  - RATIONALE: One of the major complaints most people face during aging is an
      impairment in cognitive functioning. This has a negative impact on the quality of
      daily life and is even more prominent in patients suffering from
      neurodegenerative and psychiatric disorders including Alzheimer's disease,
      schizophrenia, and depression. So far, the majority of cognition enhancers are
      generally targeting one particular neurotransmitter system. However, recently
      phosphodiesterases (PDEs) have gained increased attention as a potential new
      target for cognition enhancement. Inhibition of PDEs increases the intracellular
      availability of the second messengers cGMP and/or cAMP. OBJECTIVE: The aim of
      this review was to provide an overview of the effects of phosphodiesterase
      inhibitors (PDE-Is) on cognition, the possible underlying mechanisms, and the
      relationship to current theories about memory formation. MATERIALS AND METHODS:
      Studies of the effects of inhibitors of different PDE families (2, 4, 5, 9, and
      10) on cognition were reviewed. In addition, studies related to PDE-Is and blood
      flow, emotional arousal, and long-term potentiation (LTP) were described.
      RESULTS: PDE-Is have a positive effect on several aspects of cognition, including
      information processing, attention, memory, and executive functioning. At present,
      these data are likely to be explained in terms of an LTP-related mechanism of
      action. CONCLUSION: PDE-Is are a promising target for cognition enhancement; the
      most suitable candidates appear to be PDE2-Is or PDE9-Is. The future for PDE-Is
      as cognition enhancers lies in the development of isoform-specific PDE-Is that
      have limited aversive side effects.

PMID- 18709360
TI  - Discriminative stimulus properties of the atypical antidepressant, mirtazapine,
      in rats: a pharmacological characterization.
AB  - RATIONALE: Though interoceptive properties of antidepressants have been
      described, discriminative stimulus (DS) properties of mirtazapine, which does not
      affect monoamine reuptake, remain uncharacterized. OBJECTIVES: The objectives of
      the study are to train rats to recognize a mirtazapine DS, then perform
      substitution studies with other antidepressants and drugs acting at sites
      occupied by mirtazapine. MATERIALS AND METHODS: Using a two-lever, fixed-ratio 10
      schedule, rats were trained to discriminate mirtazapine (2.5 mg/kg, i.p.) from
      saline. RESULTS: Sessions, 63 +/- 8, were necessary to reach the criterion for 14
      rats that all subsequently recognized (100%) mirtazapine at the training dose.
      Mirtazapine blocks serotonin (5-HT)(2C) receptors, and the 5-HT(2C) antagonists,
      SB242,084, SB243,213 and S32006, revealed dose-dependent and full (> or =80%)
      substitution at doses of 2.5, 2.5, and 0.63 mg/kg, respectively. By contrast, the
      5-HT(2A) antagonists, MDL100,907 and SR46349-B, the 5-HT(2B) antagonist,
      SB204,741, and the 5-HT(3) antagonist, ondansetron, showed no significant
      substitution. Though mirtazapine indirectly recruits 5-HT(1A) receptors, the 5
      HT(1A) agonists, buspirone and 8-OH-DPAT, did not substitute. Mirtazapine blocks
      alpha(2)-adrenoceptors, but several alpha(2)-adrenoceptor antagonists (yohimbine,
      RX821,002 and atipamezole) failed to substitute. Despite blockade by mirtazapine
      of histamine H(1) receptors, no substitution was seen with the selective H(1)
      antagonist, pyrilamine. Finally, the selective noradrenaline reuptake inhibitor,
      reboxetine (0.16), fully substituted for mirtazapine, whereas the 5
      HT/noradrenaline reuptake inhibitors, duloxetine and S33005, several 5-HT
      reuptake inhibitors (citalopram, fluvoxamine, and paroxetine) and the dopamine
      reuptake inhibitors, bupropion and GBR12,935, did not substitute. CONCLUSION:
      Mirtazapine elicits a DS in rats for which selective antagonists at 5-HT(2C)
      receptors display dose-dependent substitution, whereas drugs acting at other
      sites recognized by mirtazapine are ineffective.

PMID- 18709362
TI  - Separation and characterization of oxaliplatin dinucleotides from DNA using HPLC
      ESI ion trap mass spectrometry.
AB  - Oxaliplatin is a third-generation platinum complex, and has a broad spectrum of
      antitumor activity. Such platinum complexes with the DACH carrier ligand have
      recently received increasing attention since they show efficacy against cisplatin
      resistant cell lines. As the foremost indication of antitumor activity of
      platinum drugs is the formation of adducts with genomic DNA, calf thymus DNA
      oxaliplatin adducts were the major target in this study. Calf thymus DNA was
      incubated with oxaliplatin, resulting in the formation of a large number of
      platinum-DNA adducts. Treated DNA was digested into the dinucleotides with a
      combination of enzymes, namely, benzonase, alkaline phosphatase, and nuclease S1.
      Using a high-performance liquid chromatography, we carried out the separation of
      individual platinum-DNA adducts which were concurrently identified using
      electrospray ionization ion trap mass spectrometry (MS). Both 1,2-intrastrand and
      1,2-interstrand cross-linked adducts were found; however, those of the
      intrastrand nature have a considerably higher abundance than those of the
      interstrand cross-links. Among them, d(GpG)-oxaliplatin was the most abundant
      bifuctional adduct. To a lesser extent, a few monofunctional adducts were
      detected as well. MS(n) experiments served to ascertain the detailed structures
      of oxaliplatin adducts of dinucleoside monophosphates and of dinucleotides.

PMID- 18709363
TI  - MALDI-TOF/TOF CID study of poly(alpha-methylstyrene) fragmentation reactions.
AB  - MALDI-TOF/TOF CID experiments are reported for hydroxylated poly(alpha
      methylstyrene) precursor ions (PAMS: m/z 1,445.9 (n = 10), 2,036.3 (n = 15),
      2,626.7 (n = 20), 3,217.1 (n = 25), and 3,807.5 (n = 30), where the number of
      repeat units n corresponds to the oligomer mass numbers). The influences of
      structure, molecular weight, and kinetic energy on degradation mechanisms were
      examined to test the generality of our multi-chain fragmentation model developed
      for polystyrene. Our results indicate that poly(alpha-methylstyrene) free
      radicals are formed initially through multiple chain breaks and subsequently
      undergo a variety of depolymerization reactions to yield predominantly monomer
      and dimer species; the intensity of each species depends on the effective kinetic
      energy selected for the CID process. Each depolymerization mechanism is presented
      in detail with experimental and computational data to justify/rationalize the
      process and its kinetic energy dependence. These processes show the complex
      interrelationships between the various pathways along with preferred production
      of tertiary radicals, which suppresses the appearance of primary radicals.
      Additionally, Py-GC/MS experimental data are presented to allow a comparison of
      the multimolecular free radical reactions in pyrolysis with the unimolecular
      fragmentation reactions of MS/MS.

PMID- 18709364
TI  - Cold hyposensitivity after topical application of capsaicin in humans.
AB  - Capsaicin activates the transient receptor potential vanilloid 1 receptor (TRPV1)
      on small sensory afferents, and capsaicin is commonly used to elucidate
      mechanisms of neuropathic pain. This study was performed to describe changes in
      cold and cold pain perception after topically applied capsaicin. Fourteen healthy
      subjects were included. Cold detection and cold pain thresholds and the response
      to suprathreshold cold stimuli were evaluated before and after topical
      application of capsaicin (200 microl, 50 mg/ml in 70% ethanol solution, 10.2 cm2)
      for 30 min. The skin temperature was kept between 34 and 35 degrees C. At the
      site of capsaicin application (the primary area), we found profound cold
      hypoesthesia and hypoalgesia, while outside the application site (the secondary
      area) there were no difference in the changes in cold detection and cold pain
      thresholds and cold-induced pain compared to the control arm. These results
      suggest a peripheral mediated decrease in cold sensation following TPRV1 receptor
      activation.

PMID- 18709365
TI  - The sense of agency and its disturbances in schizophrenia: a reappraisal.
AB  - How it happens that one can recognise oneself as the source of one's own actions?
      This process of self-recognition is in fact far from trivial: although it
      operates covertly and effortlessly, it depends upon a set of mechanisms involving
      the processing of specific neural signals, from sensory as well as from central
      origin. In this paper, experimental situations where these signals can be
      dissociated from each other and where self-recognition becomes ambiguous will be
      used in healthy subjects and in schizophrenic patients. These situations will
      reveal that there are two levels of self-recognition, an automatic level for
      action identification, and a conscious level for the sense of agency, which both
      rely on the same principle of congruence of the action-related signals. The
      automatic level provides an immediate signal for controlling and adapting actions
      to their goal, whereas the conscious level provides information about the
      intentions, plans and desires of the author of these actions. The contribution of
      schizophrenic patients is to show that these two levels can be dissociated from
      each other. Whereas the automatic self-identification is functional in these
      patients, their sense of agency is deeply impaired: the first rank symptoms,
      which represent one of the major features of the disease, testify to the loss of
      the ability of schizophrenic patients to attribute their own thoughts, internal
      speech, covert or overt actions to themselves.

PMID- 18709366
TI  - The use of predictive information is impaired in the actions of children and
      young adults with Developmental Coordination Disorder.
AB  - The need for a movement response may often be preceded by some advance
      information regarding direction or extent. We examined the ability of individuals
      with Developmental Coordination Disorder (DCD) to organise a movement in response
      to advance information. Pre-cues were presented and varied in the extent to which
      they indicated the response target. Both eye movement latencies and hand
      movements were measured. In the absence of pre-cues, individuals with DCD were as
      fast in initial hand movements as the typically developing (TD) participants, but
      were less efficient at correcting initial directional errors. A major difference
      was seen in the degree to which each group could use advance pre-cue information.
      TD participants were able to use pre-cue information to refine their actions. For
      the individuals with DCD this was only effective if there was no ambiguity in the
      advance cue and they had particular difficulty in using predictive motion cues.
      There were no differences in the speed of gaze responses which excluded an
      explanation relating to the dynamic allocation of attention. Individuals with DCD
      continued to rely on the slower strategy of fixating the target prior to
      initiating a hand movement, rather than using advance information to set initial
      movement parameters.

PMID- 18709368
TI  - Expression of serotonin derivative synthetic genes on a single self-processing
      polypeptide and the production of serotonin derivatives in microbes.
AB  - The plant-specific serotonin derivatives feruloylserotonin (FS) and 4
      coumaroylserotonin (CS) are synthesized by the enzymes 4-coumarate:coenzyme A
      ligase (4CL) and serotonin N-hydroxycinnamoyltransferase (SHT). To express these
      genes coordinately, SHT was fused in-frame with the self-processing FDMV 2A
      sequence followed by 4CL in a single open reading frame and introduced into
      Escherichia coli or Saccharomyces cerevisiae. The transgenes were abundantly
      expressed in both recombinant microbes, but functional expression was achieved
      only in yeast, with cleavage at the 2A sequence yielding monomeric SHT-2A and 4CL
      as judged by immunoblot and product analyses. In the presence of an exogenous
      supply of precursors such as serotonin and ferulic acid, the recombinant yeast
      synthesized 4.5 mg l(-1) FS in the medium while 0.02 mg l(-1) FS was produced in
      the cells. Time-course analysis indicated peak accumulation of FS at 24 h after
      induction, and this level was maintained until 96 h. The optimum precursor
      concentration was 2 mM. A series of serotonin derivatives was produced by adding
      various cinnamate derivative precursors with serotonin; 2.5 mg l(-1)
      caffeoylserotonin (CaS) and 1.4 mg l(-1) CS were produced, whereas no
      sinapoylserotonin or cinnamoylserotonin was yielded.

PMID- 18709367
TI  - Hypnotizability-dependent modulation of postural control: effects of alteration
      of the visual and leg proprioceptive inputs.
AB  - The aim of the experiment was to investigate whether the peculiar
      attentional/imagery abilities associated with susceptibility to hypnosis might
      make postural control in highly hypnotizable subjects (Highs) that are less
      vulnerable to sensory alteration than in individuals with low hypnotic
      susceptibility (Lows). The movement of the centre of pression (CoP) was monitored
      in Highs and Lows during alteration of the visual and leg proprioceptive input.
      The two groups responded differently to eyes closure and to an unstable support
      and the CoP movement was generally larger and faster in Highs. The stabilogram
      diffusion analysis indicated a different set point in Highs and Lows and
      suggested that the former are more independent of specific sensory information
      than the latter, likely due to different abilities in sensory re-weighting and/or
      peculiar internal models of postural control. The results are discussed within
      the general perspective of high pervasiveness of the hypnotizability trait, which
      modulates cognitive, autonomic and somatic functions.

PMID- 18709369
TI  - Usefulness of competitive inhibitors of protein binding for improving the
      pharmacokinetics of 186Re-MAG3-conjugated bisphosphonate (186Re-MAG3-HBP), an
      agent for treatment of painful bone metastases.
AB  - PURPOSE: We have developed a (186)Re-mercaptoacetylglycylglycylglycine complex
      conjugated bisphosphonate ((186)Re-MAG3-HBP) for the treatment of painful bone
      metastases. We assumed competitive inhibitors of protein binding to be useful for
      procuring a favorable biodistribution of (186)Re-MAG3-HBP for the palliation of
      bone pain because it has been reported that the concurrent administration of
      (99m)Tc-MAG3 and drugs with high affinity for serum protein produced competitive
      displacement at specific binding sites and enhanced total clearance and tissue
      distribution. METHODS: The displacement effects of several protein-binding
      inhibitors on the protein binding of (186)Re-MAG3-HBP were investigated.
      Biodistribution experiments were performed by intravenously administering (186)Re
      MAG3-HBP into rats with ceftriaxone as a competitive protein-binding inhibitor or
      saline. RESULTS: The protein binding of (186)Re-MAG3-HBP in rat serum, human
      serum, and a human serum albumin solution was significantly decreased by the
      addition of ceftriaxone, which has high affinity for binding site I on serum
      albumin. In the biodistribution experiments, pretreatment with ceftriaxone
      enhanced the clearance of the radioactivity of (186)Re-MAG3-HBP in blood and
      nontarget tissues but had no effect on accumulation in bone. CONCLUSIONS: The
      findings suggested that the use of protein-binding competitive inhibitors would
      be effective in improving the pharmacokinetics of radiopharmaceuticals with high
      affinity for serum protein.

PMID- 18709370
TI  - [Differential diagnosis of synovitis].
AB  - The synovial membrane is a site where many diseases with different etiologies can
      become manifest. Tumors and storage diseases are some of the rare conditions,
      whereas crystal deposition diseases, acute bacterial infections and in particular
      chronic uncharacteristic synovitis are frequently encountered. The latter present
      a diagnostic problem, because they can barely be assigned to concrete diagnoses.
      This report will give an overview of the differential diagnosis of joint diseases
      and will focus on the so-called synovitis score as a tool for the systematic
      evaluation of chronic uncharacteristic synovitis, providing a possibility to
      differentiate between degenerative and rheumatic synovitis with a specificity of
      60.5% and a sensitivity of 95.5%.

PMID- 18709371
TI  - [Ovarian carcinoma. Do the subtypes reflect different diseases?].
AB  - Lack of therapeutic options and poor reproducibility of histopathological
      subtypes have been the reasons that ovarian carcinomas are currently treated as
      monolithic entity. Histopathological grading is used to identify those patients
      who can be spared adjuvant therapy. With slight modifications of the WHO based
      subtype classification we have shown that subtypes (i.e. serous, endometrioid,
      clear cell, mucinous) can be reproducibly used to stratify patients according to
      disease-specific survival. As these pathologically identifiable subtypes have
      different epidemiologic and genetic risk factors, precursor lesions, molecular
      abnormalities and clinical behaviour, screening and management strategies have to
      be subtype-specific.

PMID- 18709372
TI  - Joint and nail involvement in Turkish patients with psoriatic arthritis.
AB  - Psoriatic arthritis is an autoimmune, chronic, systemic inflammatory disorder
      characterized by the association of arthritis with psoriasis. In this paper, we
      explore the characteristics of joint and nail involvement in Turkish patients
      with psoriatic arthritis. Forty patients with psoriasis (M/F, 18/22) and 49 (M/F,
      25/24) subjects with psoriatic arthritis were included in the study. Clinical
      characteristics of the patients were recorded. The distribution of the subjects
      with arthritis: (according to the clinical and radiological findings):
      polyarticular, 65%; oligoarticular, 23%; isolated axial involvement, 7.7%;
      arthritis mutilans, 3.8%; sacroiliitis, 19%. Nail involvement was significantly
      higher among patients with arthritis; i.e., 91 versus 32%; (P<0.05). There were
      no correlation between the skin involvement pattern and the arthritis type
      (P>0.05). Nevertheless, no relation was observed between the psoriasis duration
      and arthritis (P>0.05). Nail involvement is a frequent feature of the psoriatic
      arthritis which may be a useful finding for differential diagnosis of psoriatic
      arthritis from other inflammatory arthropathies.

PMID- 18709374
TI  - [Fulminant process of an orbital Mucoracea infection].
AB  - Rhinoorbitocerebral mucormycosis is a rare invasive fungal infection that is
      fatal when untreated. We describe an immunosuppressed patient with chronic
      lymphatic leukaemia who developed a severe rhinoorbitocerebral mucormycosis after
      allogeneic bone marrow transplantation. Due to the potentially fulminant course
      and fatal outcome, radical excision of the necrotic area in combination with
      antifungal therapy is necessary in the presence of suspicious clinical signs of
      mucormycosis despite a lack of histopathologic confirmation.

PMID- 18709373
TI  - T1rho, T2 and focal knee cartilage abnormalities in physically active and
      sedentary healthy subjects versus early OA patients--a 3.0-Tesla MRI study.
AB  - (1) To assess the degree of focal cartilage abnormalities in physically active
      and sedentary healthy subjects as well as in patients with early osteoarthritis
      (OA). (2) To determine the diagnostic value of T2 and T1rho measurements in
      identifying asymptomatic physically active subjects with focal cartilage lesions.
      Thirteen asymptomatic physically active subjects, 7 asymptomatic sedentary
      subjects, and 17 patients with mild OA underwent 3.0-T MRI of the knee joint.
      T1rho and T2 values, cartilage volume and thickness, as well as the WORMS scores
      were obtained. Nine out of 13 active healthy subjects had focal cartilage
      abnormalities. T1rho and T2 values in active subjects with and without focal
      cartilage abnormalities differed significantly (p < 0.05). T1rho and T2 values
      were significantly higher (p < 0.05) in early OA patients compared to healthy
      subjects. T1rho measurements were superior to T2 in differentiating OA patients
      from healthy subjects, yet T1rho was moderately age-dependent. (1) Active
      subjects showed a high prevalence of focal cartilage abnormalities and (2) active
      subjects with and without focal cartilage abnormalities had different T1rho and
      T2 composition of cartilage. Thus, T1rho and T2 could be a parameter suited to
      identify active healthy subjects at higher risk for developing cartilage
      pathology.

PMID- 18709375
TI  - [Neovascular age-related macular degeneration in Germany. Encroachment on the
      quality of life and the financial implications].
AB  - BACKGROUND: Approximately 35,000 cases of neovascular age-related macular
      degeneration (AMD) occur annually in Germany. The neovascular form of AMD (NV
      AMD) is responsible for severe vision loss associated with the disease in 90% of
      the cases. This study was conducted to assess the humanistic and economic burden
      of NV-AMD in the German population. METHODS: A cross-sectional, observational
      study of subject self-reported functional health, well-being, and disease burden
      among elderly subjects with (n=83) and without (n=93) NV-AMD in Germany was
      conducted. Patients participated in telephone surveys involving the National Eye
      Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQol (EQ-5D), the
      Hospital Anxiety and Depression Scale (HADS), and also reported history of falls,
      fractures, and healthcare resource utilization. Furthermore, the healthcare
      utilization and unit costs for the NV-AMD patients were calculated. RESULTS: The
      mean age of NV-AMD patients was 77.2 years and 64% were female. NV-AMD patients
      reported significantly worse vision-related function and overall well-being than
      controls (adjusted mean scores: NEI-VFQ-25 overall scale: 51.3 vs 96.3; p<0.0001)
      and significantly more depression symptoms than controls (HADS depression: 6.2
      vs. 2.7; p<0.0001). NV-AMD patients also reported that the need for assistance
      with daily activities was more than 10 times greater compared to controls (26.5%
      vs. 2.2%; p<0.0001) and the prevalence of falls was 3 times that of the control
      group (13.3% vs 4.3%; p=0.031). Annual NV-AMD costs per patient were <euro> 9871,
      6 times that of elderly patients without NV-AMD (<euro> 1559). Of the NV-AMD
      costs one-half were direct non-medical-related costs (assistance of ADL or social
      benefit) and one-third were direct medical costs. CONCLUSIONS: NV-AMD is
      associated with decreased functional abilities and quality of life, which result
      in an increase in healthcare resource utilization. Consequently, costs were
      higher for NV-AMD patients compared to controls. These findings emphasize the
      need for new NV-AMD treatments that will prevent vision loss and progression to
      blindness, and lessen the ensuing economic burden. Sponsored by Pfizer Inc. New
      York, US.

PMID- 18709376
TI  - [Spontaneous resolution of vitreomacular traction syndrome].
AB  - Incomplete posterior vitreous detachment may lead to anterior posterior and
      tangential traction to the macula. At the location of the attachment, a cystoid
      retinal degeneration develops. The causative therapy in such cases is a pars
      plana vitrectomy (ppV) to release the vitreomacular traction. Only a few cases of
      spontaneous resolution of traction macular edema are described in the literature.
      Long-standing macular edema may damage the photoreceptors; therefore, ppV should
      be planned because only about 10% of cases of vitreomacular traction syndrome
      resolve spontaneously.

PMID- 18709377
TI  - Mechanical filtering by the boundary layer and fluid-structure interaction in the
      superficial neuromast of the fish lateral line system.
AB  - A great diversity of aquatic animals detects water flow with ciliated
      mechanoreceptors on the body's surface. In order to understand how these
      receptors mechanically filter signals, we developed a theoretical model of the
      superficial neuromast in the fish lateral line system. The cupula of the
      neuromast was modeled as a cylindrical beam that deflects in response to an
      oscillating flow field. Its accuracy was verified by comparison with prior
      measurements of cupular deflection in larval zebrafish (Danio rerio). The model
      predicts that the boundary layer of flow over the body attenuates low-frequency
      stimuli. The fluid-structure interaction between this flow and the cupula
      attenuates high-frequency stimuli. The number and height of hair cell kinocilia
      and the dimensions of the cupular matrix determine the range of intermediate
      frequencies to which a neuromast is sensitive. By articulating the individual
      mechanical contributions of the boundary layer and the components of cupular
      morphology, this model provides the theoretical framework for understanding how a
      hydrodynamic receptor filters flow signals.

PMID- 18709378
TI  - Sex steroid-induced inhibition of food intake in sea bass (Dicentrarchus labrax).
AB  - This study was conducted to test the sensitivity to gonadal steroids of the
      systems regulating food intake in sea bass. Animals were treated with silastic
      implants containing 17-beta-estradiol or testosterone. Self-feeding was recorded
      for 31 days using computerized demand feeders and unfed-pellet recovery systems.
      Both steroids strongly decreased self-feeding levels, feed efficiency and
      specific growth rates. The linear growth of fish treated with testosterone was
      higher than in 17-beta-estradiol treated fish. In the second experiment, fish
      were treated with lower 17-beta-estradiol doses and 11-keto-androstenedione, a
      precursor of the main fish androgen (11-keto-testosterone). The results
      demonstrated a dose-response effect of estrogen and no effect of non-aromatizable
      androgens on food intake or growth performance. The inhibitory effect of
      testosterone on food intake seems to be mediated by its aromatization to
      estradiol, while linear growth promotion is mediated by the androgen per se. Data
      suggest that gonadal steroids may be involved in the seasonal feeding pattern of
      sea bass. The results demonstrate the sensitivity of the mechanisms regulating
      food intake to estrogenic compounds and point to the risk of including feed
      containing estrogenic substances in fish diets as well as the risk involved in
      exposure to "estrogenic environments".

PMID- 18709379
TI  - A modification of the McLaughlin procedure for persistent posterior shoulder
      instability: technical note.
AB  - We describe a modification of the McLaughlin procedure for persistent posterior
      shoulder instability following posterior glenohumeral dislocation with a large
      antero-medial reverse Hill-Sachs lesion. In the original McLaughlin description,
      the subscapularis was divided close to its insertion to the lesser tuberosity and
      sutured into the reverse Hill-Sachs lesion using bone drill holes. In our newly
      described technique, the subscapularis tendon is not divided but is instead
      plicated into the reverse Hill-Sachs lesion using suture anchors inserted in the
      humeral head defect. We present the case of a patient with persistent posterior
      instability following traumatic posterior glenohumeral dislocation, successfully
      treated with our new technique.

PMID- 18709380
TI  - Impact of variants in the VEGF gene on progression of proliferative diabetic
      retinopathy.
AB  - BACKGROUND: The development of diabetic retinopathy is associated with the
      duration of diabetes and HbA1c levels. However, the familial aggregation of
      diabetic retinopathy is consistent with genetic susceptibility. Recently, a 
      634C/G polymorphism in the vascular endothelial growth factor (VEGF) gene was
      shown to be associated with diabetic retinopathy. To clarify the contribution of
      the VEGF gene in the development of diabetic retinopathy we analyzed variants in
      this gene among 469 Japanese patients with type 2 diabetes. METHODS: DNA from
      each patient was typed for -634C/G and -2578C/A polymorphisms using conventional
      polymerase chain reaction techniques. The vitreous fluid samples were obtained
      from 40 patients with PDR for measurement of VEGF levels. RESULTS: We found a
      significantly higher frequency of the A allele in the group with proliferative
      diabetic retinopathy (PDR) than in the control group at -2578C/A polymorphism (p
      = 0.036). Moreover, if the subjects were grouped according to the duration of
      diabetes and status of diabetic retinopathy (a first group consisting of subjects
      with longer duration (>20 y) of diabetes without any retinopathy (n = 102), and a
      second group of those with shorter diabetes (<15 y) but having retinopathy (n =
      35), the genotype distribution at -2578 C/A polymorphism was again significantly
      higher in the second group (p = 0.005) and differed significantly (p = 0.002) in
      a recessive model. The risk of the AA for PDR was 7.7 (95%, CI: 1.8-30.9).
      CONCLUSIONS: The AA genotype at -2578C/A polymorphism in the VEGF gene is
      associated with proliferative diabetic retinopathy. No significant association
      with -634 C/G polymorphism was confirmed.

PMID- 18709381
TI  - Drusenoid maculopathy in rhesus monkeys (Macaca mulatta): effects of age and
      gender.
AB  - PURPOSE: To compare drusenoid maculopathy in monkeys with human age-related
      macular degeneration, and evaluate the influence of age, gender and caloric
      restriction. METHODS: Examination by indirect ophthalmoscopy, slit-lamp
      biomicroscopy and fundus photography, including in some cases fluorescein
      angiography, was performed on 61 male and 60 female rhesus macaques of ages 10-39
      years. Fifty-four of the monkeys were maintained on a calorically restricted diet
      (approximately 30% lower than control levels) and 67 on an approximately ad
      libitum diet for 2-19 years, with all other environmental factors held constant.
      Maculopathies were graded on a 5-point scale and the effects of age, sex, and
      diet on prevalence and severity were examined. The retinas of six monkeys with
      macular drusen, 19-28 years old, were examined histologically. RESULTS: Rhesus
      monkeys showed a high prevalence (61%) of drusenoid maculopathy. The prevalence
      and severity of the maculopathy increased with age (p = 0.012). Fully half of all
      monkeys aged 10-12 years had some detectable degree of drusen. This high
      prevalence in young adulthood indicates that drusen develop much earlier in
      rhesus monkeys than in humans, who develop early maculopathy most rapidly at 50
      60 years of age, even when correcting for the 3-fold difference in lifespan. No
      neovascularization or geographic atrophy was found. Females had a higher
      prevalence and severity than males (p = 0.019). Calorically restricted monkeys
      had a slightly lower prevalence and severity at 10-12 years than controls, but
      the difference was not statistically significant. This is an on-going project,
      and differences between the caloric restricted and ad-lib groups may emerge as
      the animals age. Some monkeys developed severe maculopathy in their 20s, with
      others unaffected in their 30s. The histology of drusen resembled those in human
      retina. CONCLUSION: Drusenoid maculopathy is common in rhesus monkeys, even in
      young adult life. Half of the rhesus monkeys examined have drusen at a much
      younger age than in humans. Severity of maculopathy was greater in female
      monkeys, a gender difference not consistently found in humans. No differences
      were detected due to caloric restriction, but a definitive test of this
      intervention will require a larger sample, longer period of observation, and/or
      an earlier institution of caloric restriction. Genetic factors are implied
      because with similar environments, some monkeys are affected at an early age,
      while older ones are not.

PMID- 18709382
TI  - Results of macular pucker surgery: 1- and 5-year follow-up.
AB  - BACKGROUND: Although macular pucker removal in patients with metamorphopsia due
      to a macular pucker is a traditional elective vitreoretinal indication, we found
      that patients were not uniformly satisfied after surgery. We wished to study
      outcome in vision and metamorphopsia in patients undergoing macular pucker
      surgery, to assess changes between 1- and 5-year follow-up, as well as patient
      satisfaction at 5 years. METHODS: We assessed 107 consecutive patients undergoing
      macular pucker surgery and subsequent cataract surgery when not already
      pseudophakic. Early Treatment of Diabetes Study (EDTRS) vision and Sine Amsler
      Chart metamorphopsia grading were assessed before surgery and 1 year postop in
      107 patients. In 57 patients we obtained a 5-year vision, metamorphopsia grading
      and a response to a questionnaire. RESULTS: After 1 year, mean vision had
      improved 2 ETDRS lines and metamorphopsia had decreased in 83% of the patients.
      The 57 patients returning for the 5-year follow-up and questionnaire had a
      statistically significantly greater improvement in vision at 1 year than those
      who did not return. In these 57 patients, a further mean increase of 1 ETDRS line
      had occurred, as well as a further decrease in metamorphopsia in one third of the
      patients. Forty of 57 patients (70%) indicated that they would elect to have
      surgery again. Reasons for not returning after 5 years, however, were probably
      related to dissatisfaction in at least one third of patients. CONCLUSIONS:
      Although macular pucker surgery resulted in an increase in vision and a decrease
      of metamorphopsia in 83% of patients after 1 year, we assume, based on the biased
      patient sample we questioned after 5 years, that subjective assessment would be
      positive in only a small majority of the patients.

PMID- 18709383
TI  - Upregulation of stromal cell-derived factor 1 (SDF-1) expression in
      microvasculature endothelial cells in retinal ischemia-reperfusion injury.
AB  - BACKGROUND: Stromal cell-derived factor 1 (SDF-1) is a potent chemotactic and
      angiogenic factor that has been proposed to play a role in the development of
      neovascularization. In this study, we explored the expression of SDF-1 in a rat
      model of retinal ischemia-reperfusion injury and investigated the possible role
      of retinal microvasculature endothelium cells in generation of this chemokine.
      METHODS: Expression patterns of SDF-1 were studied in retina suffering ischemia
      reperfusion insult in Sprague-Dawley rats by elevating the intraocular pressure
      to 110 mm for 60 minutes. The relative level of SDF-1 mRNA in retinas following
      6, 12 and 24 hours reperfusion was determined by semi-quantitative RT-PCR.
      Immunohistochemical methods were used to detect specific lesions expressing SDF
      1. The gene expression of SDF-1 in cultured human retinal microvasculature
      endothelial cells (HRMEC) under hypoxia conditions was assessed by semi
      quantitative RT-PCR. The SDF-1 protein was analyzed by immunocytochemistry and
      fluorescence-activated cell sorting. RESULTS: Upregulation of SDF-1 mRNA (at 6,
      12, and 24 hours of reperfusion) was observed, with the expression peak occurring
      at 12 hours. SDF-1 positive cells appeared initially around the retinal
      vessels,which diffused into the inner retinal layers. Hypoxia enhanced the
      expression of HIF-1 and SDF-1 mRNA in HRMEC. The production of SDF-1 protein by
      HRMEC was increased up to 320% after 6 hours of hypoxia, as demonstrated by
      fluorescence-activated cell sorting. CONCLUSIONS: The results of our study
      indicate that endogenous SDF-1 is up-regulated in retinal microvasculature
      suffering ischemia insult, and that microvasculature endothelial cells are
      potential contributors for generation of SDF-1 in ischemic retina.

PMID- 18709384
TI  - Combined intravitreal triamcinolone injection and laser photocoagulation in eyes
      with persistent macular edema after branch retinal vein occlusion.
AB  - BACKGROUND: To determine the efficacy of combined intravitreal triamcinolone (TA)
      injection and laser photocoagulation in persistent macular edema after branch
      retinal vein occlusion (BRVO). METHODS: Follow-up analysis of a case series of 24
      patients with macular edema after BRVO (15 of 24 non-ischaemic, 9 of 24
      ischaemic). Patients received an intravitreal injection of 4 mg TA followed by
      laser photocoagulation within the previously edematous area, applied in one or
      two sessions. Standardized clinical examinations included best corrected visual
      acuity testing, anterior and posterior segment biomicroscopy, intraocular
      pressure, and optical coherence tomography (OCT). Fluorescein angiography was
      performed before treatment and 3 and 6 months later. RESULTS: Median visual
      acuity improved significantly from 0.58 logMAR (95%-confidence interval (KI):
      0.54-0.75, decimal 0.27) at baseline to 0.41 logMAR (KI: 0.37-0.64, decimal 0.39)
      at 1 month (p = 0.001), 0.33 logMAR (KI: 0.32-0.62, decimal 0.47) at 3 months (p
      = 0.002), and 0.41 logMAR (KI: 0.33-0.67, decimal 0.39) at 6 months (p = 0.016).
      A gain of one or more logarithmic lines was evaluated in 16/24 eyes (67 %) and a
      gain of 3 lines or more in 8/24 eyes (33 %) at 6 months. Three eyes had lost more
      than 1 line during the follow-up period. Median change of visual acuity at 6
      months was +2.0 lines (KI: 0.2-2.4). Median central foveal thickness (OCT-CFT)
      was 423 microm (KI: 378-456, n = 24) at baseline and decreased to 270 microm (KI:
      249-311, n = 24) at 1 month (p < 0.0001), 265 microm (KI: 254-344, n = 24) at 3
      months (p < 0.0001), and 266 microm (KI: 259-365, n = 18) at 6 months (p =
      0.001). CONCLUSIONS: Macular edema after BRVO can effectively be treated by a
      combination of intravitreal TA injection and subsequent laser photocoagulation.
      During a 6-month follow-up this combination treatment resulted in a significant
      reduction of central foveal thickness and improvement of visual acuity.

PMID- 18709386
TI  - Expression and function of K(v)7 channels in murine myometrium throughout
      oestrous cycle.
AB  - This study represents an extensive characterisation of the expression and
      functional impact of KCNQ and KCNE accessory subunits in a murine uterus using a
      combination of quantitative reverse transcription polymerase chain reaction,
      Western blot analysis, patch clamp electrophysiology and isometric tension
      recording. The use of uterine tissue throughout the oestrous cycle provided a
      physiological model with which to assess hormonal regulation of these genes.
      Messenger ribonucleic acid for all KCNQ genes were detected throughout the
      oestrous cycle with the KCNQ1 message predominant. KCNE isoforms were detected at
      each stage of the cycle. KCNE4 was the most abundant (p < 0.0001), and KCNQ1,
      KCNQ5 and KCNE1 were up-regulated in metestrous (p < 0.0001). The K(v)7 channel
      inhibitor XE991 reduced outward K(+) currents and significantly increased
      spontaneous myometrial contractions (p < 0.05), whereas retigabine (K(v)7
      activator) significantly relaxed uterine tissues (p < 0.001). These data are the
      first to characterise KCNQ and KCNE gene expression in a cell type outside of
      neurons and the cardiovascular system.

PMID- 18709385
TI  - A review of in vivo animal studies in retinal prosthesis research.
AB  - BACKGROUND: The development of a functional retinal prosthesis for acquired
      blindness is a great challenge. Rapid progress in the field over the last 15
      years would not have been possible without extensive animal experimentation
      pertaining to device design and fabrication, biocompatibility, stimulation
      parameters and functional responses. This paper presents an overview of in vivo
      animal research related to retinal prosthetics, and aims to summarize the
      relevant studies. METHODS: A Pubmed search of the English language literature was
      performed. The key search terms were: retinal implant, retinal prosthesis,
      artificial vision, rat, rabbit, cat, dog, sheep, pig, minipig. In addition a
      manual search was performed based on references quoted in the articles retrieved
      through Pubmed. RESULTS: We identified 50 articles relevant to in vivo animal
      experimentation directly related to the development of a retinal implant. The
      highest number of publications related to the cat (n = 18). CONCLUSION: The
      contribution of animal models to the development of retinal prosthetic devices
      has been enormous, and has led to human feasibility studies. Grey areas remain
      regarding long-term tissue-implant interactions, biomaterials, prosthesis design
      and neural adaptation. Animals will continue to play a key role in this rapidly
      evolving field.

PMID- 18709388
TI  - Life cycle polyphenism as a factor affecting ecological divergence within
      Notophthalmus viridescens.
AB  - Polyphenism, which allows a single genotype to express multiple discrete
      phenotypes in response to environmental cues, is an adaptive trait in
      heterogeneous environments. Pond hydroperiod is an important ecological parameter
      affecting amphibian life history, and variation in local pond hydrology has been
      hypothesized to play a role in species divergence via changes in polyphenism. The
      eastern newt (Notophthalmus viridescens) expresses life cycle polyphenism. Larvae
      develop along three possible pathways: metamorphosis to aquatic lunged adult via
      a terrestrial juvenile (eft) stage, metamorphosis directly to an aquatic lunged
      adult, or maturation directly to an aquatic gilled adult without metamorphosis
      (i.e., paedomorphosis). Subspecies of N. viridescens vary in their polyphenic
      patterns, suggesting possible adaptation to different environments. However, no
      studies have experimentally tested how genetic and environmental components
      contribute to the observed differences among subspecies and whether such
      differences may facilitate divergence. We tested whether adaptation to local pond
      hydrology via polyphenic changes existed among subspecies by rearing larvae of
      three subspecies (N. v. dorsalis, N. v. louisianensis, and N. v. viridescens)
      along three hydroperiod regimes (short, long, and constant) in outdoor artificial
      ponds. We found that larval N. v. viridescens obligately metamorphosed to efts
      under all hydroperiods, whereas N. v. dorsalis and N. v. louisianensis exhibited
      plasticity: larvae metamorphosed to efts under drying conditions but
      metamorphosed directly to aquatic adults or became paedomorphic in constant
      water. Also, N. v. viridescens metamorphosed to efts faster and at a smaller body
      size than the other two subspecies. These data suggest that subspecies of N.
      viridescens are adapted to different pond hydroperiods, supporting the potential
      for polyphenism to facilitate divergence. Canalizing selection for certain
      alternative phenotypes within a single species in which other populations remain
      plastic may play an important role in the initiation of ecological divergence.

PMID- 18709387
TI  - Prevalence and molecular characterization of human and bovine Cryptosporidium
      isolates in Thailand.
AB  - This study was performed to determine the prevalence and genotypes of
      Cryptosporidium species among HIV patients and cattle in Thailand. Stool
      specimens were collected from 46 HIV patients from Prabat Nampu Temple, Lop Buri
      Province in central Thailand. Two hundred fecal samples from dairy cattle were
      collected from seven farms in Chon Buri Province, the eastern part of Thailand.
      Each sample was concentrated by Sheather's sucrose flotation technique and
      stained by acid fast stain (AFS) for the identification of oocysts by microscopy.
      All HIV stool samples and 83 fecal specimens from cattle were further tested
      using nested polymerase chain reaction (PCR) targeting the 18S SSUrRNA gene to
      characterize the detected species. In HIV patient samples, the detection rate was
      28.7% by AFS and 4.35% by nested PCR. In cattle samples, the detection rate was
      13% by AFS and 9.63% by nested PCR. After DNA sequencing results, we identified
      the genotypes of the Cryptosporidium from seven of the PCR positive samples. All
      were found to be C. parvum. The findings presented here represent the first
      genetic identification of Cryptosporidium species in cattle in Thailand.

PMID- 18709389
TI  - Using stable isotopes to assess carbon and nitrogen turnover in the Arctic
      sympagic amphipod Onisimus litoralis.
AB  - Food web studies based on stable C and N isotope ratios usually assume isotopic
      equilibrium between a consumer and its diet. In the Arctic, strong seasonality in
      food availability often leads to diet switching, resulting in a consumer's
      isotopic composition to be in flux between different food sources. Experimental
      work investigating the time course and dynamics of isotopic change in Arctic
      fauna has been lacking, although these data are crucial for accurate
      interpretation of food web relationships. We investigated seasonal (ice-covered
      spring vs. ice-free summer) and temperature (1 vs. 4 degrees C) effects on growth
      and stable C and N isotopic change in the common nearshore Arctic amphipod
      Onisimus litoralis following a diet switch and while fasting in the laboratory.
      In spring we found no significant temperature effect on N turnover [half-life
      (HL) estimates: HL-N = 20.4 at 4 degrees C, 22.4 days at 1 degrees C] and a
      nonsignificant trend for faster growth and C turnover at the higher temperature
      (HL-C = 13.9 at 4 degrees C, 18.7 days at 1 degrees C). A strong seasonal effect
      was found, with significantly slower growth and C and N turnover in the ice-free
      summer period (HL-N = 115.5 days, HL-C = 77.0 days). Contrary to previous
      studies, metabolic processes rather than growth accounted for most of the change
      in C and N isotopic composition (84-89 and 67-77%, respectively). This study
      provides the first isotopic change and metabolic turnover rates for an Arctic
      marine invertebrate and demonstrates the risk of generalizing turnover rates
      based on taxon, physiology, and environment. Our results highlight the importance
      of experimental work to determine turnover rates for species of interest.

PMID- 18709390
TI  - Hydatid disease: a cause of renal cystic masses in children.

PMID- 18709391
TI  - Genetic forms of nephrotic syndrome: a single-center experience in Brussels.
AB  - The aim of the study was to present our experience in treating children with
      genetic forms of nephrotic syndrome and diagnosing these diseases. We
      retrospectively reviewed the clinical data, mutational analyses,
      histopathological features, treatment modalities, and outcome of 26 consecutive
      children (20 families) suffering from congenital and/or steroid-resistant
      nephrotic syndrome who were assessed by genetic analysis. Ten out of 26 children
      (38%) had congenital nephrotic syndrome, 4/26 (15%) had infantile nephrotic
      syndrome, 10/26 (38%) had late-onset nephrotic syndrome, and 2/26 (9%) had
      asymptomatic proteinuria. We detected a mutation in 21/26 (81%) patients and in
      15/20 (75%) families. NPHS1 mutation analyses were positive in 4/20 (20%), NPHS2
      mutations in 4/20 (20%), WT1 mutations in 4/20 (20%), and PLCE1 mutations in 3/20
      (15%) families. NPHS1 and PLCE1 mutations were solely found in patients with the
      earliest onset. The majority of patients, especially those with early onset of
      nephrotic syndrome, had serious adverse events related to the nephrotic status,
      and 19/26 (73%) reached end-stage renal failure at a median age of 27 months.
      Genetic forms of nephrotic syndrome comprise a heterogeneous group of genetic
      mutations. The progression toward end-stage renal failure is the rule but is
      highly variable between patients.

PMID- 18709392
TI  - Novel plant and fungal AGP-like proteins in the Medicago truncatula-Glomus
      intraradices arbuscular mycorrhizal symbiosis.
AB  - The ability of arbuscular mycorrhizal (AM) fungi to colonise the root apoplast,
      and in coordination with the plant develop specialised plant-fungal interfaces,
      is key to successful symbioses. The availability of expressed sequence tags (EST)
      of the model legume, Medicago truncatula, and AM fungus, Glomus intraradices,
      permits identification of genes required for development of symbiotic interfaces.
      The M. truncatula EST database was searched to identify cell surface
      arabinogalactan-proteins (AGPs) expressed in mycorrhizal roots. Candidate genes
      were characterised and gene expression tested using reverse transcription
      polymerase chain reaction and promoter:reporter gene fusions. Genes encoding one
      plant AGP and three AGP-like (AGL) proteins (from G. intraradices) were
      identified. AGL proteins encoded by two AGL genes from G. intraradices (GiAGLs)
      represent a new structural class of AGPs not found in non-AM fungi or plants. Two
      GiAGLs differ from plant AGPs by containing charged repeats. Structural modelling
      shows that GiAGL1 can form a polyproline II helix with separate positively and
      negatively charged faces, whereas GiAGL3 is charged on all three faces. The
      unique structural properties of the newly discovered AGLs suggests that they
      could assist the formation of symbiotic interfaces through self-assembly and
      interactions with plant cell surfaces.

PMID- 18709393
TI  - Influence of postmortem time on the outcome of blood cultures among cadaveric
      tissue donors.
AB  - Tissue banks provide tissues of human cadaver donors for transplantation. The
      maximal time limit for tissue retrieval has been set at 24 h postmortem. This
      study aimed at evaluating the evidence for this limit from a microbiological
      point of view. The delay of growth in postmortem blood cultures, the
      identification of the species isolated and clinical/environmental factors were
      investigated among 100 potential tissue donors. No significant difference was
      found in the rate of donors with grown blood cultures within (25/65=38%) compared
      with after (24/65=37%) 24 h of death. Coagulase-negative staphylococci and gastro
      intestinal microorganisms were isolated within and after 24 h of death. Two
      factors--antimicrobial therapy and "delay before body cooling"--were
      significantly inversely related with donors' blood culture results. From a
      microbiological point of view, there is no evidence for avoiding tissue retrieval
      among donors after 24 h of death.

PMID- 18709394
TI  - Efficacy of culture filtrates of Metarhizium anisopliae against larvae of
      Anopheles stephensi and Culex quinquefasciatus.
AB  - Efficacy of culture filtrates of five strains of Metarhizium anisopliae isolated
      from insects were evaluated against Anopheles stephensi and Culex
      quinquefasciatus. The culture filtrates released from the strains of M.
      anisopliae in the YpSs and chitin broths were filtered and used for the bioassays
      after a growth of 7 days. Among the culture filtrates of five strains, M.
      anisopliae 892 was found to be more effective against both the mosquitoes. The
      LC(50) values of culture filtrates of M. anisopliae 892 in chitin broth was lower
      than the LC(50) of culture filtrates in YpSs broth against first and fourth
      instars of both the mosquitoes. The LC(50) values of culture filtrates were
      significantly different between first and fourth instars of A. stephensi (t test;
      P = 0.0001) and C. quinquefasciatus (t test; P = 0.02). The larvae of A.
      stephensi were more susceptible than C. quinquefasciatus except in two cases.
      This is the first report of efficacy of culture filtrates produced by M.
      anisopliae in chitin broth against mosquitoes and have potential as a biological
      control agent of mosquitoes.

PMID- 18709395
TI  - Application of oxygen uptake rate and response surface methodology for
      erythromycin production by Saccharopolyspora erythraea.
AB  - A process for efficient production of erythromycin by Saccharopolyspora erythraea
      using statistical designs and feeding strategy was developed. The critical
      nutrient components were selected in accordance with fractional factorial design
      and were further optimized via response surface methodology. Three significant
      components (ZnSO(4), citric acid threonine) were identified for the optimization
      study. The optimum levels of these significant variables were determined with Box
      Behnken design, which were ZnSO(4) 0.039 g/l, citric acid 0.24 g/l and threonine
      0.42 g/l, respectively. A novel feeding strategy based on oxygen uptake rate
      (OUR) measurement was developed successfully to increase the flux of erythromycin
      biosynthesis, in which the optimized nutrient components was fed in the 50 l
      stirred bioreactor when OUR began to decline at 46 h. The maximum erythromycin
      production reached 10,622 U/ml, which was 11.7% higher than the control in the
      same cultivation conditions. It was the first report to integrate physiological
      parameter OUR and statistical methods to optimize erythromycin production.

PMID- 18709396
TI  - LMP-1 retroviral gene therapy influences osteoblast differentiation and fracture
      repair: a preliminary study.
AB  - LIM mineralization protein-1 (LMP-1) is a novel intracellular osteogenic factor
      associated with bone development that has been implicated in the bone
      morphogenetic protein (BMP) pathway. This preliminary study evaluated the
      possibility of LMP-1-based retroviral gene therapy to stimulate osteoblast
      differentiation in vitro and fracture repair in vivo. A Moloney leukemia virus
      (MLV)-based retroviral vector to express LMP-1 with a hemagglutinin (HA) tag was
      developed, and its effects were evaluated on MC3T3-E1 cell differentiation and in
      the rat femur fracture model. MC3T3-E1 osteoblasts transduced with the MLV-HA-LMP
      1 vector demonstrated significantly increased osteoblast marker gene expression
      (P < 0.05) and mineral deposition compared to control transduced cells. Femoral
      midshaft fractures were produced in Fischer 344 rats by the three-point bending
      technique. The MLV-HA-LMP-1 or control vector was applied at the fracture site
      through percutaneous injections 1 day postfracture. Analysis of fracture healing
      of 10 MLV-HA-LMP-1-treated and 10 control MLV-beta-galactosidase (beta-gal)
      treated animals was completed at 3 weeks by X-ray, peripheral quantitative
      computed tomography, and histology. MLV-HA-LMP-1-treated animals had 63% more
      bone mineral content at the fracture site (P < 0.01), 34% greater total hard
      callus area (P < 0.05), and 45% less cartilage in the fracture callus (P < 0.05)
      compared to MLV-beta-gal-treated animals. There was no effect of LMP-1 treatment
      on the density of the hard callus. Immunohistochemistry revealed expression of
      the LMP-1 transgene in the fracture callus at 21 days postfracture.
      Immunohistochemistry also revealed that LMP-1 transgene expression did not result
      in an increase in BMP-4 expression in the fracture callus. Compared to MLV-BMP-4
      gene therapy studies, MLV-HA-LMP-1 gene therapy improved bony union of the
      fracture gap to a greater extent and did not cause heterotopic bone formation.
      This suggests that LMP-1 may be a better potential candidate for gene therapy for
      fracture repair than BMP-4. These exciting, albeit preliminary, findings indicate
      that LMP-1-based gene therapy may potentially be a simple and effective means to
      enhance fracture repair that warrants further investigation.

PMID- 18709397
TI  - Effect of sequential isoproturon pulse exposure on Scenedesmus vacuolatus.
AB  - Aquatic organisms are typically exposed to fluctuating concentrations of
      herbicides in streams. To assess the effects on algae of repeated peak exposure
      to the herbicide isoproturon, we subjected the alga Scenedesmus vacuolatus to two
      sequential pulse exposure scenarios. Effects on growth and on the inhibition of
      the effective quantum yield of photosystem II (PSII) were measured. In the first
      scenario, algae were exposed to short, 5-h pulses at high isoproturon
      concentrations (400 and 1000 microg/l), each followed by a recovery period of 18
      h, while the second scenario consisted of 22.5-h pulses at lower concentrations
      (60 and 120 microg/l), alternating with short recovery periods (1.5 h). In
      addition, any changes in the sensitivity of the algae to isoproturon following
      sequential pulses were examined by determining the growth rate-EC(50) prior to
      and following exposure. In both exposure scenarios, we found that algal growth
      and its effective quantum yield were systematically inhibited during the
      exposures and that these effects were reversible. Sequential pulses to
      isoproturon could be considered a sequence of independent events. Nevertheless, a
      consequence of inhibited growth during the repeated exposures is the cumulative
      decrease in biomass production. Furthermore, in the second scenario, when the
      sequence of long pulses began to approach a scenario of continuous exposure, a
      slight increase in the tolerance of the algae to isoproturon was observed. These
      findings indicated that sequential pulses do affect algae during each pulse
      exposure, even if algae recover between the exposures. These observations could
      support an improved risk assessment of fluctuating exposures to reversibly acting
      herbicides.

PMID- 18709398
TI  - The arterial switch operation before Jatene.
AB  - Attempts at the arterial switch operation predated the Senning and the Mustard
      venous switch procedures. No patients survived the earlier arterial switch
      methods. Therefore, from the 1960s to the 1980s, venous switch surgeries became
      the dominant treatment method for transposition of the great arteries. The
      Brazilian cardiac surgeon, Adib Jatene, reported the first successful arterial
      switch in 1975. The history of the earlier arterial switches performed in the
      1950s and 1960s is not well known. This article discusses that early history.

PMID- 18709399
TI  - Three-dimensional computed tomographic findings of bilateral tracheal bronchus.
AB  - A newborn male was admitted with cyanosis and respiratory distress.
      Echocardiography showed a right heart isomerism associated with a single right
      ventricle, a double-outlet right ventricle, and pulmonary atresia. Chest X-ray
      demonstrated severe left upper lobe emphysema and a shift of the mediastinal
      structures to the right. Two-dimensional computed tomography (CT) exhibited left
      upper lobe emphysema and right upper lobe atelectasis. Three-dimensional (3D)
      spiral CT angiography showed a bilateral tracheal bronchus. The left tracheal
      bronchus branch was compressed between the descending aorta and the ductus
      arteriosus. After a right arteriopulmonary shunt operation, the patient's
      respiratory condition improved dramatically, with spontaneous closure of the
      ductus arteriosus. Subsequently, 3D-CT clearly exhibited the disappearance of
      tracheal compression. This combination of bilateral tracheal bronchus and
      congenital heart anomaly is extremely rare. The 3D-CT is a powerful noninvasive
      means for dynamically demonstrating the special relationships of arterial and
      tracheal anomalies.

PMID- 18709400
TI  - Cardiovascular magnetic resonance imaging for intensive care infants: safe and
      effective?
AB  - BACKGROUND: Cardiac magnetic resonance imaging (MRI) is an important diagnostic
      tool for congenital heart disease (CHD), as reflected by class 1 recommendations
      for the use of cardiac MRI by various consensus panels. However, little is known
      about the safety and clinical utility of cardiac MRI for these critically ill
      infants with CHD, whose further management cannot be directed by
      echocardiography. This study aimed to assess the safety, the potential
      hemodynamic side effects, and the clinical benefits of cardiac MRI for infants
      with complex CHD during their intensive care unit stay. METHODS: Infants referred
      from the pediatric cardiac intensive care unit (PCICU) to the authors' cardiac
      MRI program in the past 2 years were retrospectively analyzed using the
      electronic chart system available at their institution. Data collected included
      age, diagnosis, inotropic support, urine output, diuretic medication, body
      temperature and lactate levels, length of MRI examination, adverse effects during
      and after the procedure, clinical implications of MRI, length of stay in the
      PCICU, and mean blood pressure and heart rate before, during, and after MRI.
      RESULTS: Among 592 patients in the past 2 years, 20 (3.4%) were referred for MRI
      testing during their stay in the PCICU. The mean age of the infants was 4.8+/-3.2
      months. Four of the patients were neonates, and eight were postoperative
      patients. Intracardiac malformations were present in 16 of the infants, vascular
      rings causing tracheal stenosis in 3 patients, and cardiomyopathy in 1 patient.
      The mean stay in the PCICU was 28+/-43 days. Eight of the infants were
      ventilated, with a mean fraction of inspired oxygen (FiO2) of 0.30+/-0.15. Four
      were receiving inotropic support. All the nonventilated children were intubated
      for the MRI and extubated in the MRI laboratory. The mean duration of the MRI
      (door-to-door time) was 110+/-27 min. All except one patient were hemodynamically
      stable, and no increase in catecholamine support was necessary during or after
      the scans. A 10-month-old girl receiving inotropic support needed a single dose
      of epinephrine due to a short episode of bradycardia after a breathhold for a
      contrast agent MRI angiography. Mean body core temperature at arrival to the
      PCICU was 36.8+/-0.7 degrees C. The mean serum lactate level after the MRI was
      1.2+/-0.4 mmol/l. The mean blood pressure and heart rate before, during, and
      after MRI were unchanged. The mean diuresis on examination day was
      insignificantly lower (2.4%) than the day before with unchanged medication
      (5.09+/-1.58 vs 5.53+/-1.77 ml/kg/h). For 14 (70%) of the 20 patients, surgical
      or catheter interventional procedures were initiated based on novel MRI
      information. CONCLUSION: Cardiac MRI can be performed safely with low risk and
      limited hemodynamic changes for infants during their stay in the PCICU. Cardiac
      MRI provides key information for invasive management decisions in this subset of
      patients.

PMID- 18709401
TI  - Prenatal diagnosis and management of fetal Long QT syndrome.
AB  - This report describes a fetus presenting with second-degree atrioventricular
      block, sinus bradycardia, and transient ventricular tachycardia with
      ventriculoatrial dissociation. Long QT syndrome (LQTS) was suspected due to the
      association of heart rhythm disturbances and very short transmitral early
      deceleration time. This impaired relaxation of the left ventricle was explained
      by the extreme prolongation of the refractory period caused by the prolonged
      relaxation time. The infant was treated successfully with beta-blockers and
      implantation of a pacemaker. The prognosis is poor when LQTS presents utero or
      during the first week of life. To date, only a few case reports of a fetus with
      LQTS have been published.

PMID- 18709402
TI  - Interaction effects of ambient UV radiation and nutrient limitation on the toxic
      cyanobacterium Nodularia spumigena.
AB  - Nodularia spumigena is one of the dominating species during the extensive
      cyanobacterial blooms in the Baltic Sea. The blooms coincide with strong light,
      stable stratification, low ratios of dissolved inorganic nitrogen, and dissolved
      inorganic phosphorus. The ability of nitrogen fixation, a high tolerance to
      phosphorus starvation, and different photo-protective strategies (production of
      mycosporine-like amino acids, MAAs) may give N. spumigena a competitive advantage
      over other phytoplankton during the blooms. To elucidate the interactive effects
      of ambient UV radiation and nutrient limitation on the performance of N.
      spumigena, an outdoor experiment was designed. Two radiation treatments
      photosynthetic active radiation (PAR) and PAR +UV-A + UV-B (PAB) and three
      nutrient treatments were established: nutrient replete (NP), nitrogen limited (
      N), and phosphorus limited (-P). Variables measured were specific growth rate,
      heterocyst frequency, cell volume, cell concentrations of MAAs, photosynthetic
      pigments, particulate carbon (POC), particulate nitrogen (PON), and particulate
      phosphorus (POP). Ratios of particulate organic matter were calculated: POC/PON,
      POC/POP, and PON/POP. There was no interactive effect between radiation and
      nutrient limitation on the specific growth rate of N. spumigena, but there was an
      overall effect of phosphorus limitation on the variables measured. Interaction
      effects were observed for some variables; cell size (larger cells in -P PAB
      compared to other treatments) and the carotenoid canthaxanthin (highest
      concentration in -N PAR). In addition, significantly less POC and PON (mol cell(
      1)) were found in -P PAR compared to -P PAB, and the opposite radiation effect
      was observed in -N. Our study shows that despite interactive effects on some of
      the variables studied, N. spumigena tolerate high ambient UVR also under nutrient
      limiting conditions and maintain positive growth rate even under severe
      phosphorus limitation.

PMID- 18709404
TI  - Torsion of the spermatic cord: the main gray-scale and doppler sonographic signs.
AB  - Scrotal ultrasonography (US) is usually the initial imaging modality for
      evaluating patients who present with acute pathologic conditions of the scrotum.
      Acute epididymitis, acute epididymo-orchitis, torsion of the spermatic cord
      (TSC), and other acute scrotal abnormalities may have similar findings at
      clinical examination. Pain and swelling make the clinical examination difficult,
      sometimes practically impossible, potentially resulting in management delays. The
      objective of this review is to summarize the main clinical signs of the TSC and
      to illustrate and briefly discuss the US features of this entity, including gray
      scale imaging, color Doppler with spectral analysis, and power Doppler
      sonography. Although TSC can occur at any age, it is most common in adolescent
      boys. The intensity of the symptoms and the US findings vary with the duration of
      the torsion, number of twists in the spermatic cord (degree of rotation), and how
      tightly the vessels of the cord are compressed. An enlarged, more spherical, and
      diffusely hypoechogenic testis without detectable arterial and venous testicular
      flow at color and power Doppler US is considered diagnostic of acute testicular
      ischemia. The presence of a color or power Doppler signal in one part of the
      testis does not exclude TSC. Positive blood flow but significantly diminished,
      usually near or inside the mediastinum, may be found, mainly in the partial or
      incomplete TSC. Identification of a large echogenic extratesticular mass distal
      to the site of the torsion, frequently misinterpreted as a chronic epididymitis,
      can be the key to the diagnosis of TSC. When a small arterial sign is found a low
      amplitude waveform is present with an increased resistive index on the affected
      side due to a diminished, absent, or reversed diastolic flow. Gray-scale imaging,
      color Doppler, power Doppler and pulsed Doppler with spectral analysis are very
      effective to make or exclude the diagnosis of TSC.

PMID- 18709405
TI  - Multidetector CT angiography and virtual angioscopy of the abdomen.
AB  - Computed tomographic angiography (CTA) has gained wide clinical acceptance as a
      powerful diagnostic tool in the non-invasive evaluation of vascular disorders and
      has became the method of choice for the assessment of aortic pathology. In
      addition, recent advances in computed tomography (CT) technology improve the
      image quality and diagnostic performance of the procedure in the abdominal
      vascular system. In this paper, we briefly review the CTA technique and describe
      the main applications of abdominal CTA.

PMID- 18709406
TI  - Esophageal stenosis: three-dimensional multidetector CT and virtual endoscopy.
AB  - The improvement in spatial, temporal, and contrast resolutions with the newest
      multidetector computed tomographic (MDCT) scanners opens the opportunity to
      explore other applications of the virtual endoscopy technique besides the colon
      and stomach evaluation. As a non-invasive technique, virtual esophagoscopy
      represents an alternative to conventional endoscopy for the assessment of
      esophageal stenosis. The procedure and diagnostic performance are reviewed.
      Findings of this modality are illustrated.

PMID- 18709407
TI  - 64-Row multidetector CT virtual hysterosalpingography.
AB  - OBJECTIVE: To illustrate the large variety of pathologies found on 64-row
      computed tomographic (CT) virtual hysterosalpingography (CT-VHSG) in the
      evaluation of the female reproductive tract in infertile patients. MATERIAL AND
      METHODS: We prospectively evaluated CT datasets from 209 patients with diagnosis
      of infertility. CT-VHSG was performed with a 64-row CT scanner using 64 x 0.625
      mm(2) collimation and 0.9 mm slice thickness. A total volume of 20 mL of an
      iodine contrast dilution was injected into the uterine cavity. The duration of
      the CT scan and the grade of patient discomfort of the procedure were documented.
      Images were analyzed on a workstation. The CT-VHSG exams were divided in studies
      with normal or pathological findings; pathologies were classified according to
      their locations (cervical, uterine, and fallopian tube pathology). RESULTS: No
      complications occurred during the procedure. The mean scan time was 3.4 +/- 0.4
      s; the mean patient effective dose was 2.58 +/- 0.75 mSv. In relation to the
      patient's discomfort evaluation, 55.5% of the patients referred no discomfort
      during the procedure. Cervical pathology was found in 100/209 patients, uterine
      pathology in 93/209 patients, and fallopian tubes pathology in 37/209 patients.
      CONCLUSION: A 64-row CT-VHSG provides a reliable, non-invasive alternative
      diagnostic technique in the infertility workup algorithm.

PMID- 18709408
TI  - Algorithm for an aesthetically pleasing nipple-areola complex with the use of the
      C-V flap in cases of skin-sparing mastectomy and immediate reconstruction.
AB  - BACKGROUND: This article provides an algorithm for achieving an aesthetically
      pleasing nipple-areola complex in cases of skin-sparing mastectomy and immediate
      reconstruction METHODS: If the contralateral nipple was big enough and the nipple
      sharing technique could be used in the future for reconstruction, we left a round
      skin paddle at the time of the skin-sparing mastectomy and immediate flap
      reconstruction. The diameter of the round skin paddle was approximately the same
      as the contralateral areola. For nipple reconstruction we placed the graft from
      the contralateral nipple in the middle of the aforementioned skin paddle. If the
      contralateral nipple was not sufficiently large for use as a donor, then the C-V
      flap was used for nipple reconstruction. In these cases we deliberately left an
      oval skin paddle when the skin-sparing mastectomy and immediate flap
      reconstruction were performed. The short diameter of the oval skin paddle was
      approximately the same as the diameter of the contralateral areola. The position
      and the height of the C-V flap were marked in order to transform the oval skin
      paddle to a round one when the donor site of the C-V flap was closed. RESULTS:
      Following this algorithm an optical illusion of a nipple-areola complex that is
      similar to the contralateral normal one is created. CONCLUSION: From our
      experience this algorithm can help create an aesthetically pleasing nipple-areola
      complex and also provides a ready pattern to our tattoing experts for the
      dermatography of the nipple-areola complex.

PMID- 18709409
TI  - Magnetic resonance images and linear measurements in the surgical treatment of
      breast asymmetry.
AB  - BACKGROUND: Objective evaluation of breast asymmetry surgical treatment should
      consider not only breast shape but also breast volume. METHODS: For this study,
      22 patients with primary breast asymmetry were evaluated by magnetic resonance
      imaging (MRI) as well as linear measurements preoperatively and 6 months
      postoperatively. The mean difference between the pre- and postoperative linear
      measurements was graduated from excellent to poor. Breast volume was estimated by
      MRI from axial reconstruction for three-dimensional application using the
      Cavalieri formula and specific software. RESULTS: A strong correlation (r =
      0.817) was found between the pre- and postoperative breast volumes, as increased
      or decreased by the surgical procedure. Patients with less postoperative volume
      differences tended to have the best ratings with linear measurements. When the
      same surgical procedure was performed bilaterally or when only one breast was
      treated by surgery, greater volume symmetry was observed. CONCLUSIONS: Linear
      measurements and MRI are objective methods for evaluating postoperative symmetry,
      and when used in association, can help plastic surgeons to achieve favorable
      results in mammary asymmetry treatment.

PMID- 18709410
TI  - Definition procedures have little effect on performance of environmental
      classifications of streams and rivers.
AB  - Mapped environmental classifications are defined using various procedures, but
      there has been little evaluation of the differences in their ability to
      discriminate variation in independent ecological characteristics. We tested the
      performance of environmental classifications of the streams and rivers of France
      that had been defined from the same environmental data using geographic
      regionalization and numerical classification of individual river valley segments.
      Test data comprised invertebrate assemblages, water chemistry, and hydrological
      indexes obtained from sites throughout France. Classification performance was
      measured by analysis of similarity (ANOSIM). Geometric regions defined by a
      regular grid and without regard to environmental variables and a posteriori
      classifications based on clustering the test datasets defined lower and upper
      bounds of performance for a given number of classes. Differences in
      classification performances were generally small. The ANOSIM statistics for the a
      posteriori classifications were around twice that of all environmental
      classifications, including geometrically defined regions. The hydro-ecoregions
      performed slightly better for the invertebrate data and the network
      classification performed slightly better for the chemistry and hydrological data.
      Our results indicate that environmental classifications that are defined using
      different procedures can be comparable in terms of their ability to discriminate
      variation of ecological characteristics and that alleged differences in
      performance arising from different classification procedures can be small
      relative to unexplained variation. We conclude that definition procedures might
      have little effect on the performance of large-scale environmental
      classifications and decisions over which procedures to use should be based
      primarily on pragmatic considerations.

PMID- 18709411
TI  - The relationship of Mirizzi syndrome and cholecystoenteric fistula: validation of
      a modified classification.

PMID- 18709412
TI  - Cirsoid aneurysm of coronary arteries associated with arterioventricular fistula
      evaluated by 64-multidetector CT coronary angiography: depiction of a case.
AB  - A female patient with severe pulmonary hypertension was admitted for lung
      transplant evaluation. As an incidental finding, the chest CT showed diffuse and
      dilated coronaries, not detected at previous echocardiography. A coronary CT
      angiography was then performed using a 64-multidetector computed tomography
      (MDCT) scanner to better evaluate the coronary tree. The images obtained after
      postprocessing demonstrated tremendously aneurysmatic and tortuous coronary
      arteries and the presence of a septal branch deepening into the myocardium and
      penetrating the right ventricle cavity, forming an abnormal arterioventricular
      fistula. A causal relation between the aneurysms and the fistula is suspected.

PMID- 18709413
TI  - Percutaneous RF thermal ablation of renal tumors: is US guidance really less
      favorable than other imaging guidance techniques?
AB  - The purpose of this study was to compare our experience with ultrasound (US)
      guided percutaneous radiofrequency thermal ablation (RFA) of renal tumors with
      results of CT-guided and MRI-guided series in the current literature. Of 90
      consecutive renal tumors treated with RFA in 71 patients, 87 lesions were ablated
      under US guidance. We performed a retrospective analysis of clinical outcome and
      safety. Results were then compared to published case series where CT and MRI
      guidances were used exclusively. In our series we had a major complication rate
      of 4.6%, whereas in CT- and MRI-based series it was 0-12% (mean, 2.2%) and 0-8.3%
      (mean, 4.1%), respectively. During follow-up (1-68 months; mean, 24 months)
      technical effectiveness was 89.7%, while it was between 89.5% and 96% in CT
      guided series and between 91.7% and 100% in MRI-guided series. The size of
      successfully treated lesions (28 mm) was lower than that of partially-ablated
      lesions (36 mm; p = 0.004) and only central lesion location proved to be a
      negative prognostic factor (p = 0.009); in CT-guided series, positive prognostic
      factors were exophytic growth and size </=3 cm. "Tumor-specific" 2-year survival
      was 92% in our series, 90-96% in CT-guided series, and not reported in MRI-guided
      series. In conclusion, despite common beliefs, US guidance in RFA of renal tumors
      is not less favorable than other guidance techniques. Thus the interventional
      radiologist can choose his or her preferred technique taking into account
      personal experience and available equipment.

PMID- 18709414
TI  - A new scoring system for gallbladder cancer: the first step of a long walk.

PMID- 18709415
TI  - Radiofrequency thermal ablation of breast cancer local recurrence: a phase II
      clinical trial.
AB  - BACKGROUND: The role of radiofrequency (RF) ablation to treat local recurrence of
      breast cancer is unknown. METHODS: We conducted a two-stage phase II clinical
      trial. Eligible patients had a histologically confirmed noninflammatory and < or
      =3 cm ipsilateral breast tumor recurrence. The tumor site was identified by
      intraoperative sonography. A LeVeen needle electrode (RadioTherapeutics Corp,
      Mountain View, Calif) was inserted into a single site within the tumor and
      radiofrequency ablation was performed using a RF-2000 generator
      (RadioTherapeutics Corp). After completion of radiofrequency, a mastectomy was
      performed. Conventional staining and nicotinamide adenine dinucleotide-diaphorase
      (NADH-diaphorase) cell viability staining were performed. RESULTS: During the
      first stage, procedures were uneventful. Conventional, cytokeratin, and NADH
      diaphorase staining identified persistent viable tumor cells in the RF-ablated
      region in three patients. This phase II trial was stopped after completion of the
      first stage because of insufficient efficacy. CONCLUSION: We demonstrate in this
      study that RF ablation is a potential technique to destroy local recurrence of
      breast tumors but the technique we tested in this phase II clinical trial had
      insufficient efficacy to recommend its use in routine.

PMID- 18709416
TI  - Axillary reverse mapping in breast cancer: a new microsurgical lymphatic-venous
      procedure in the prevention of arm lymphedema.

PMID- 18709417
TI  - Persistence and spread of gastro-intestinal infections: the case of
      enterotoxigenic Escherichia coli in piglets.
AB  - Several gastro-intestinal infections in animal husbandry not only greatly reduce
      the well-being of animals, but also have the potential to cause large economical
      damage. Understanding of the dynamics of such diseases is thus of great
      importance. In this paper, we focus on within-host dynamics and present a model
      describing the dynamics of pathogens in the intestine of a single host. Our
      motivation to study the problem stems from the case of enterotoxigenic
      Escherichia coli in newly weaned piglets, but the models we present offer an
      acceptable description of within-host dynamics of several other gastro-intestinal
      infections. We begin by studying the case where infection is a one-time event and
      derive an explicit expression for the distribution of pathogens inside the
      intestine at an arbitrary time after the infection took place. Since farm animals
      often come into contact with faeces, we furthermore investigate the reinfection
      case, in which a fraction of the shed pathogens is reintroduced into the
      intestine. We find the condition that guarantees persistence of colonization in
      the reinfection case and determine when the microbial distribution in the
      intestine obeys the so called asynchronous exponential growth. We outline
      possibilities for infection control and point out some challenges for further
      research on the subject.

PMID- 18709418
TI  - Surgical management of early-stage hepatocellular carcinoma: resection or
      transplantation?
AB  - BACKGROUND: The surgical management of hepatocellular carcinoma in patients with
      well-compensated cirrhosis is controversial. The purpose of the current study was
      to compare the outcome of patients with well-compensated cirrhosis and early
      stage hepatocellular carcinoma treated with initial hepatic resection versus
      transplantation. METHODS: Between 1985 and 2008, 245 patients underwent hepatic
      resection, and 134 patients underwent liver transplantation for early stage
      hepatocellular carcinoma. All patients had well-compensated cirrhosis. Prognostic
      factors were evaluated using univariate and multivariate analyses; survival was
      calculated using the Kaplan-Meier method. RESULTS: Compared with transplantation,
      patients undergoing resection had larger tumors and a higher incidence of
      microscopic vascular invasion. Transplantation was associated with better 5-year
      disease-free and overall survival compared with resection. Hepatitis status,
      presence of microscopic vascular invasion, and tumor size were predictors for
      recurrence, while the presence of microscopic vascular invasion and tumor size
      conferred an increased risk of death. The disease-free survival advantage with
      transplantation was more pronounced in hepatitis C patients compared with non
      hepatitis and hepatitis B patients. The overall survival advantage with
      transplantation persisted in cases of solitary lesions < or = 3 cm, but was
      attenuated in patients with a MELD score < or = 8. CONCLUSION: In well
      compensated cirrhotic patients with early stage hepatocellular carcinoma,
      transplantation was associated with longer disease-free and overall survival.
      Patients undergoing resection did, however, have tumors with more advanced
      pathologic features. Patients best suited for initial resection as the treatment
      of hepatocellular carcinoma were those with a MELD score </= 8 without evidence
      of hepatitis.

PMID- 18709419
TI  - Long-term results of transanal excision after neoadjuvant chemoradiation for T2
      and T3 adenocarcinomas of the rectum.
AB  - INTRODUCTION: Traditionally, selected early distal rectal cancers have been
      considered for treatment by transanal excision (TAE) with acceptable oncologic
      results. With the frequent use of neoadjuvant chemoradiation (NCR) for the
      treatment of locally advanced rectal cancer, there is growing interest in the
      application of TAE for such lesions. We report our experience of TAE for T2 and
      T3 rectal cancers following NCR. MATERIAL AND METHODS: Between July 1994 and
      August 2006, 44 patients were identified as having undergone full-thickness TAE
      of pretreatment ultrasound-staged T2 and T3 rectal cancers that were treated with
      NCR. Fifteen patients were deemed medically unfit for radical resection, and 29
      would have required abdominoperineal resection but were opposed to colostomy.
      RESULTS: Our patient population consisted of 26 men and 18 women, with a median
      age of 69 (range, 43-89) and a median follow up of 64 months (6-153). Thirty-one
      patients had a clinical complete response (cCR) to NCR of which 19 (61%) had a
      pathologic CR (pCR). Seven (16%) of 44 patients sustained disease recurrence of
      which two were local only, two local and systemic, and three systemic only. Only
      four (9%) patients had died of disease at current follow up. Overall 5-year
      survival rates for T2/T3N0 and T2/T3N1 patients were 84% and 81%, respectively.
      Five patients underwent radical resection immediately following TAE for either
      positive margins or residual cancer. There was minimal morbidity with no
      perioperative mortality associated with TAE. CONCLUSIONS: TAE of T2 and T3 rectal
      cancers following NCR is a safe alternative to radical resection in a highly
      select group of patients for which recurrence and survival rates comparable to
      radical resection can be achieved. This study supports ongoing efforts to assess
      this approach in prospective, multi-center trials.

PMID- 18709420
TI  - Use of infliximab within 3 months of ileocolonic resection is associated with
      adverse postoperative outcomes in Crohn's patients.
AB  - BACKGROUND: Few studies have evaluated preoperative infliximab use and
      postoperative outcomes in Crohn's patients. Our aim was to evaluate 30-day
      postoperative outcomes for Crohn's patients treated with infliximab within 3
      months prior to ileocolonic resection. METHODS: The study is a retrospective
      evaluation of data for patients undergoing ileocolonic resection after 1998 from
      a prospective Crohn's disease database. Patient characteristics and 30-day
      complications were compared for patients treated with infliximab within 3 months
      before surgery and an infliximab naive group. The infliximab group was also
      compared with non-infliximab patients undergoing ileocolonic surgery before 1998.
      RESULTS: Sixty of 389 Crohn's patients undergoing ileocolonic resection received
      infliximab. The infliximab and non-infliximab groups had similar characteristics,
      preoperative risk factors, and surgical procedure. However, steroid use was
      higher (p < 0.05) in the non-infliximab group while concurrent immunosuppressive
      use was higher (p < 0.001) in the infliximab group. Multivariate analysis showed
      infliximab use to be associated with 30-day postoperative readmission (p =
      0.045), sepsis (p = 0.027), and intraabdominal abscess (p = 0.005). The presence
      of diverting stoma (n = 17) in the infliximab group was associated with lower
      risk of sepsis (0% vs. 27.9%, p = 0.013). Similar results were noted when the
      infliximab group was compared to the pre-infliximab patients. CONCLUSIONS:
      Infliximab use within 3 months before surgery is associated with increased
      postoperative sepsis, abscess, and readmissions in Crohn's patients. Diverting
      stoma may protect against these complications.

PMID- 18709421
TI  - Surgical management of failed endoscopic treatment of pancreatic disease.
AB  - INTRODUCTION: Endoscopic therapy of acute and chronic pancreatitis has decreased
      the need for operative intervention. However, a significant proportion of
      patients treated endoscopically require definitive surgical management for
      persistent symptoms. OBJECTIVE: Our aim was to determine which patients are
      likely to fail with endoscopic therapy, and to assess the clinical outcome of
      surgical management. Patients were identified using ICD-9 codes for pancreatic
      disease as well as CPT codes for endoscopic therapy followed by surgery. MATERIAL
      AND METHODS: Patients with documented acute or chronic pancreatitis treated
      endoscopically prior to surgical therapy were included (N = 88). The majority of
      patients (65%) exhibited chronic pancreatitis due to alcohol abuse. Common
      indicators for surgery were: persistent symptoms, anatomy not amenable to
      endoscopic treatment and unresolved common bile duct or pancreatic duct
      strictures. Surgical salvage procedures included internal drainage of a
      pseudocyst or an obstructed pancreatic duct (46%), debridement of peripancreatic
      fluid collections (25%), and pancreatic resection (31%). RESULTS: Death occurred
      in 3% of patients. The most common complications were hemorrhage (16%), wound
      infection (13%), and pulmonary complications (11%). Chronic pancreatitis with
      persistent symptoms is the most common reason for pancreatic surgery following
      endoscopic therapy. Surgical salvage therapy can largely be accomplished by
      drainage procedures, but pancreatic resection is common. CONCLUSION: These
      complex procedures can be performed with acceptable mortality but also with
      significant risk for morbidity.

PMID- 18709422
TI  - Outcome of right colectomy for cancer in octogenarians.
AB  - BACKGROUND: Colorectal cancer is one of the commonest malignancies in the elderly
      and, as such, is a major cause of morbidity and mortality. There is no consensus
      yet if age itself is a risk factor for adverse outcome after colectomy. The aims
      of the study were to evaluate the impact of age on operative results of right
      colectomy for cancer and to define factors that influence the postoperative
      mortality in octogenarians. METHODS: Data of all patients who underwent right
      colectomy for colon cancer between January 2001 and December 2006 were collected
      retrospectively. Patients were divided into two groups: those who were 80 years
      and older and those who were less than 80 years old. Analysis included patients'
      demographics, comorbidities, American Society of Anesthesiologists class,
      functional status, mode of presentation, stage of disease, length of hospital
      stay, postoperative morbidity, and mortality. RESULTS: A total of 124 consecutive
      patients with right colon cancer were operated. Control group included 84
      patients less than 80 year old. Study group included 40 patients 80 years or
      older. In Cox multivariate regression analysis, poor functional status and
      emergent surgery were independent factors for postoperative mortality.
      CONCLUSIONS: There was no significant difference in the outcome of elective right
      colectomy between elderly patients and their younger counterparts. Operative
      mortality of emergency surgery was significantly higher in octogenarians.
      Emergent setting and poor functional status are major risk factors for
      postoperative mortality.

PMID- 18709423
TI  - Laparoscopic transumbilical cholecystectomy without visible abdominal scars.
AB  - INTRODUCTION: We present a novel surgical technique for cholecystectomy utilizing
      three laparoscopic ports placed through the umbilicus. This new method is natural
      orifice transumbilical surgery (NOTUS) and describes a laparoscopic operation
      that can be performed with all incisions placed within the umbilicus obviating
      visible abdominal scars. OBJECTIVES: To develop a novel laparoscopic surgical
      technique for cholecystectomy utilizing only transumbilical incisions. Natural
      orifice translumenal endoscopic surgery (NOTES) has become an exciting area of
      surgical development. Significant limitations to this surgical concept, however,
      are lack of surgical expertise and appropriate flexible instrumentation. An
      alternative and competing technology to NOTES is NOTUS. METHODS: We describe a
      patient in whom a laparoscopic surgical technique for cholecystectomy utilized
      incisions all placed entirely within the umbilicus. This new technique is called
      NOTUS and describes a laparoscopic operation that can be performed without
      visible abdominal scar. RESULTS: The operative time was 70 min. There were no
      intraoperative complications. The patient did well postoperatively and was
      discharged on the same operative day. There were no postoperative complications
      at 2 months follow-up. CONCLUSION: Cholecystectomy performed through laparoscopic
      incisions placed within the umbilicus was technically feasible and safe in our
      patient. Development of advanced flexible instrumentation and visualization
      platforms may facilitate this new operative approach. Further advantages of NOTUS
      cholecystectomy compared to conventional laparoscopic cholecystectomy will
      ultimately require a randomized clinical trial.

PMID- 18709424
TI  - VEGF gene therapy augments localized angiogenesis and promotes anastomotic wound
      healing: a pilot study in a clinically relevant animal model.
AB  - BACKGROUND: Anastomotic leak related to ischemia is a source of significant
      morbidity and mortality in gastrointestinal surgery. The aim of this study was to
      apply growth factor gene transfection for the purpose of up-regulating
      angiogenesis, increasing anastomotic strength, and ultimately preventing
      dehiscence. METHODS: An opossum esophagogastrostomy model was employed. The human
      vascular endothelial growth factor (VEGF(165)) gene was incorporated into a
      recombinant plasmid. The VEGF plasmid vector was then complexed with a cationic
      synthetic carrier, polyethyleneimine. Control animals received plasmid devoid of
      VEGF(165) (n = 6). The experimental group received VEGF(165) plasmid (n = 5).
      After esophagogastrectomy and gastric tubularization, plasmid was injected into
      the submucosa of the neoesophagus at the anastomotic site. Conduit arteriography
      was performed before and 10 days after injection. Euthanasia occurred on post
      injection day 10 and the anastomosis was removed en bloc. A second group of
      animals treated with VEGF(165) were euthanized 30 and 37 days post injection.
      Blood flow was measured with laser-Doppler prior to euthanasia. Ex vivo
      anastomotic bursting pressure was performed. Tissue samples were procured for RNA
      extraction and von Willebrand Factor staining. Microvessel counts were obtained
      by two blinded observers. Tissue VEGF transcript levels were measured with
      reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: There was one
      anastomotic leak in the control group. Experimental animals demonstrated
      significantly increased bursting pressure (104.25 +/- 6.2 vs 86.73 +/- 9.4 mmHg,
      p = 0.021) and neovascularization (33.87 +/- 9.6 vs 20.33 +/- 8.1 vessels/hpf, p
      = 0.032) compared to controls. In addition, there was a strongly positive
      correlation between the number of microvessels and bursting pressure (r = 0.808,
      p = 0.015, Pearson's). On angiographic examination, treated animals demonstrated
      more neovascularization compared to controls. RT-PCR demonstrated up to a 5.6
      fold increase in VEGF mRNA in treated compared to controls. DISCUSSION: This
      description of gene therapy in gastrointestinal surgery using VEGF(165)
      transfection demonstrates increased angiogenesis with subsequently improved
      anastomotic healing in a clinically relevant model.

PMID- 18709426
TI  - Proceedings of the Association of Bone and Joint Surgeons Carl T. Brighten
      Workshop on Musculoskeletal Trauma in Low and Middle Income Countries. December
      11-14, 2007. Ahmedabad, India.

PMID- 18709425
TI  - Applying proteomic-based biomarker tools for the accurate diagnosis of pancreatic
      cancer.
AB  - BACKGROUND: The proteome varies with physiologic and disease states. Few studies
      have been reported that differentiate the proteome of those with pancreatic
      cancer. AIM: To apply proteomic-based technologies to body fluids. To
      differentiate pancreatic neoplasia from nonneoplastic pancreatic disease.
      METHODS: Samples from 50 patients (15 healthy (H), 24 cancer (Ca), 11 chronic
      pancreatitis (CP)) were prospectively collected and underwent analysis. A high
      throughput method, using high-affinity solid lipophilic extraction resins,
      enriched low molecular weight proteins for extraction with a high-speed 200-Hz
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometer
      (MALDI-MS; Bruker Ultraflex III). Samples underwent software processing with
      FlexAnalysis, Clinprot, MatLab, and Statistica (baseline, align, and normalize
      spectra). Nonparametric pairwise statistics, multidimensional scaling,
      hierarchical analysis, and leave-one-out cross validation completed the analysis.
      Sensitivity (sn) and specificity (sp) of group comparisons were determined. Two
      top-down-directed protein identification approaches were combined with MALDI-MS
      and tandem mass spectrometry to fully characterize the most significant protein
      biomarker. RESULTS: Using eight serum features, we differentiated Ca from H (sn
      88%, sp 93%), Ca from CP (sn 88%, sp 30%), and Ca from both H and CP combined (sn
      88%, sp 66%). In addition, nine features obtained from urine differentiated Ca
      from both H and CP combined with high efficiency (sn 90%, sp 90%). Interestingly,
      the plasma samples (considered by the Human Proteome Organization to be the
      preferred biological fluid) did not show significant differences.
      Multidimensional scaling indicated that markers from both serum and urine led to
      a highly effective clinical indicator of each specific disease state.
      CONCLUSIONS: The proteomic analysis of noninvasively acquired biological fluids
      provided a high level of predictability for diagnosing pancreatic cancer. While
      the proteomic analysis of serum was capable of screening individuals for
      pancreatic disease (i.e., CP and Ca vs. H), specific urine biomarkers further
      distinguished malignancy (Ca) from chronic inflammation (CP).

PMID- 18709427
TI  - Persisting high levels of synovial fluid markers after cartilage repair: a pilot
      study.
AB  - Local attempts to repair a cartilage lesion could cause increased levels of
      anabolic and catabolic factors in the synovial fluid. After repair with
      regenerated cartilage, the homeostasis of the cartilage ideally would return to
      normal. In this pilot study, we first hypothesized levels of synovial fluid
      markers would be higher in patients with cartilage lesions than in patients with
      no cartilage lesions, and then we hypothesized the levels of synovial fluid
      markers would decrease after cartilage repair. We collected synovial fluid
      samples from 10 patients before autologous chondrocyte transplantation of the
      knee. One year later, a second set of samples was collected and arthroscopic
      evaluation of the repair site was performed. Fifteen patients undergoing knee
      arthroscopy for various symptoms but with no apparent cartilage lesions served as
      control subjects. We measured synovial fluid matrix metalloproteinase-3 (MMP-3)
      and insulinlike growth factor-I (IGF-I) concentrations with specific activity and
      enzyme-linked immunosorbent assays, respectively. The levels of MMP-3 and IGF-I
      were higher in patients having cartilage lesions than in control subjects with no
      cartilage lesions. One year after cartilage repair, the lesions were filled with
      repair tissue, but the levels of MMP-3 and IGF-I remained elevated, indicating
      either graft remodeling or early degeneration. LEVEL OF EVIDENCE: Level III,
      prognostic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 18709428
TI  - Men versus women: does size matter in total knee arthroplasty?
AB  - The role played by femoral component sizing in the clinical outcome of primary
      TKA is currently debated. Oversizing the femur in patients with smaller knees
      could lead to overstuffing the knee capsule with resulting pain and reduced range
      of motion. We asked whether the distribution of femoral component sizes differed
      between genders and whether the availability of additional sizes benefited
      genders differently and led to a measurable improvement in knee flexion and Knee
      Society scores or pain. We retrospectively examined two groups of consecutive
      knees of patients who underwent primary TKA using similar techniques and
      constraint: Group 1 (93 men and 90 women) who had available four original sizes
      and Group 2 (106 men and 106 women) after the introduction of three new smaller
      sizes. More than twice as many new smaller sizes were used in women (52.3%, 56 of
      106) compared to men (17.9%, 19 of 106). At the scheduled 6-month followup visit
      (average, 6 months; range, 5-7 months), we found no differences in the knee
      score, pain score, and knee flexion in men and women before the additional sizes
      (Group 1) and after the new sizes (Group 2). Additional sizes therefore did not
      appear to influence short-term outcomes. LEVEL OF EVIDENCE: Level III,
      therapeutic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 18709429
TI  - Determining femoral component position using CAS and measured resection.
AB  - To evaluate the ability of computer-assisted surgery (CAS) to accurately size and
      determine rotational alignment of the femoral component in TKA, the author
      reviewed femoral component position after 50 consecutive primary TKAs using a
      femur-first, measured resection workflow. The computer software used allowed
      femoral rotation to be selected based on epicondylar axis, posterior condylar
      axis, or anteroposterior axis. The final femoral component size and position was
      determined by the surgeon to avoid anterior notching, match the posterior-medial
      condyle resection, and flexed to match the plane of the anterior femoral cortex.
      Femoral sizing was confirmed intraoperatively with a standard sizing guide. The
      femoral component was downsized in 52% of patients from the size recommended by
      the computer software. The posterior condylar axis matched the implanted
      rotational position of the femoral component to within 1 degrees in 64% of
      patients in contrast to the epicondylar axis (32%) and anteroposterior axis
      (26%). CAS provides information to make surgical decisions but does not replace
      clinical judgment. Landmark referencing may be compromised by limited surgical
      exposures leading to variation in implant positioning by computer software. A
      clear understanding of the principles of TKA is critical when using CAS to
      optimize implant sizing and position.

PMID- 18709430
TI  - Lateral retinacular release rates in mobile- versus fixed-bearing TKA.
AB  - Controversy exists as to whether bearing mobility facilitates centralization of
      the extensor mechanism after TKA. To assess the incidence of lateral retinacular
      release, we retrospectively reviewed 1318 consecutive primary TKAs (1032
      patients) performed by one surgeon using either a rotating-platform bearing (940)
      or a fixed bearing (378) from the same implant system. The selection of a fixed-
      versus mobile-bearing TKA was primarily based on age with patients younger than
      70 years receiving a mobile-bearing TKA. We performed a lateral release whenever
      continuous symmetric patellar facet contact with the trochlear groove from 0
      degrees to 90 degrees of flexion was not obtained using the rule of no thumb
      after tourniquet release. One hundred four of 1318 knees (7.9%) had a lateral
      release. We performed more lateral releases in the fixed-bearing group (14.3% [54
      of 378]) than in the mobile-bearing group (5.3% [50 of 940]). Patellar tilt
      occurred more often in the mobile-bearing group (10% [94 of 940]) than in the
      fixed-bearing group (6.9% [26 of 378]), although the magnitude of mean patellar
      tilt was small in both groups (mobile-bearing 3.0 degrees ; fixed bearing 2.55
      degrees ). No patient had patellar subluxation greater than 5 mm. We suspect the
      fewer lateral releases in the mobile-bearing group is the result of better
      extensor mechanism centralization provided by bearing rotation. LEVEL OF
      EVIDENCE: Level III, prognostic study. See the Guidelines for a complete
      description of levels of evidence.

PMID- 18709431
TI  - Stemmed implants improve stability in augmented constrained condylar knees.
AB  - We previously combined experimental and computational measures to ascertain
      whether tibial stem augmentation reduces bone strains beneath constrained
      condylar implants. Using these same integrated approaches, we examined the
      benefit of a stem when a wedge is used. Implants were removed from the eight
      paired cadaver specimens from our previous experiment, and oblique defects
      created that were restored with 15 degrees metallic wedges cemented in place. We
      applied a varus moment and an axial load and monitored relative motion between
      implant and bone. Specimen-specific 3-D finite element models were constructed
      from CT scans and radiographs to examine bone stress in the proximal tibia.
      Implants with a wedge but no stem had greater motion than the previous control
      with no stem or wedge. Use of a modular stem with a wedge maintained the same
      level of motion as the primary case, suggesting that a stem is preferable when a
      wedge is utilized. The computational models confirmed this conclusion with a 30%
      reduction in bone stress compared to 17% in the primary case without a wedge. The
      wedge carried more axial load compared to the primary implant due to its support
      on stiff metaphyseal bone.

PMID- 18709432
TI  - Patient-reported outcome correlates with knee function after a single-design
      mobile-bearing TKA.
AB  - With substantial interest devoted to improving knee flexion after TKA, it is
      important to document the relationship between high range of motion and patient
      rated outcomes shown. We therefore asked whether single-design high-flexion
      mobile-bearing posterior-stabilized TKA resulted in: (1) improved knee function;
      (2) satisfying subjective results; (3) participation recreational and sporting
      activities; and (4) function correlated to the final range of motion. We
      prospectively followed 445 consecutive patients having 516 TKAs from September
      2000 to January 2005. The same high-flexion posterior-stabilized mobile-bearing
      implant was used in all patients. Mean patient age was 71 +/- 8 years and mean
      body mass index was 28 +/- 4 kg/m(2). The minimum clinical followup was 2 years
      (mean, 3 years; range, 2-4 years). The postoperative range of knee flexion was
      128 degrees +/- 4 degrees and the mean Knee Society function and knee scores were
      91 +/- 6 and 96 +/- 3, respectively. Eighty-two percent of patients were involved
      in sporting activities and 86% returned to their previous level of activity.
      These data confirm that high postoperative range of knee flexion improve patient
      rated outcomes. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 18709433
TI  - Association of spinal deformities with heavy metal bioaccumulation in natural
      populations of grass goby, Zosterisessor ophiocephalus Pallas, 1811 from the Gulf
      of Gabes (Tunisia).
AB  - The present study illustrates an analysis of spinal deformities associated with
      metal accumulation in natural populations of Zosterisessor ophiocephalus derived
      from polluted (S1) and unpolluted (S2) areas in the Gulf of Gabes in Tunisia.
      Three basic types of spinal deformities were detected: kyphosis, scoliosis and
      lordosis. These basic deformities frequently co-occur. Spinal deformities were
      observed in 10.72% of the total examined fish (n = 494). Deformed fish were 3.85
      times more frequent in S1 than in S2. In both sexes, the highest occurrence of
      deformities was observed in the 111-120 mm class decreasing thereafter with fish
      length. Hepatic concentrations of cadmium (Cd), copper (Cu) and zinc (Zn) were
      significantly higher in Z. ophiocephalus from S1 than those from S2. Comparisons
      between fish in each site showed that liver concentrations of Cd and Zn were
      significantly higher in deformed fish than in normal fish. The relationship
      between metals accumulation and observed spinal deformities as well as the
      suitability of this kind of studies for environmental monitoring are discussed.

PMID- 18709434
TI  - Air quality of Prague: traffic as a main pollution source.
AB  - Political and economical transition in the Central and Eastern Europe at the end
      of eighties significantly influenced all aspects of life as well as technological
      infrastructure. Collapse of outdated energy demanding industry and adoption of
      environmental legislation resulted in seeming improvements of urban environmental
      quality. Hand in hand with modernization the newly adopted regulations also
      helped to phase out low quality coal frequently used for domestic heating.
      However, at the same time, the number of vehicles registered in the city
      increased. The two processes interestingly acted as parallel but antagonistic
      forces. To interpret the trends in urban air quality of Prague, Czech capital,
      monthly averages of PM(10), SO(2), NO(2), NO, O(3) and CO concentrations from the
      national network of automated monitoring stations were analyzed together with
      long term trends in fuel consumption and number of vehicles registered in Prague
      within a period of 1992-2005. The results showed that concentrations of SO(2) (a
      pollutant strongly related to fossil fuel burning) dropped significantly during
      the period of concern. Similarly NO(X) and PM(10) concentrations decreased
      significantly in the first half of the nineties (as a result of solid fuel use
      drop), but remained rather stable or increased after 2000, presumably reflecting
      rapid increase of traffic density. In conclusion, infrastructural changes in
      early nineties had a strong positive effect on Prague air quality namely in the
      first half of the period studied, nevertheless, the current trend in
      concentrations of automotive exhaust related pollutants (such as PM(10), NO(X))
      needs adoption of stricter measures.

PMID- 18709435
TI  - Image analysis applied to the classic microscopic method in animal meal
      characterization.

PMID- 18709436
TI  - Nerve stimulator-guided paravertebral lumbar plexus anaesthesia in dogs.

PMID- 18709437
TI  - Transgenic mice expressing the Peripherin-EGFP genomic reporter display intrinsic
      peripheral nervous system fluorescence.
AB  - The development of homologous recombination methods for the precise modification
      of bacterial artificial chromosomes has allowed the introduction of disease
      causing mutations or fluorescent reporter genes into human loci for functional
      studies. We have introduced the EGFP gene into the human PRPH-1 locus to create
      the Peripherin-EGFP (hPRPH1-G) genomic reporter construct. The hPRPH1-G reporter
      was used to create transgenic mice with an intrinsically fluorescent peripheral
      nervous system (PNS). During development, hPRPH1-G expression was concomitant
      with the acquisition of neuronal cell fate and growing axons could be observed in
      whole embryo mounts. In the adult, sensory neurons were labeled in both the PNS
      and central nervous system, while motor neurons in the spinal cord had more
      limited expression. The fusion protein labeled long neuronal processes,
      highlighting the peripheral circuitry of hPRPH1-G transgenic mice to provide a
      useful resource for a range of neurobiological applications.

PMID- 18709438
TI  - Risk factors for treatment failure in renal suppurative infections.
AB  - There are conflicting results of published studies about prognostic value of
      various factors in purulent renal infections. The purpose of this study was to
      identify and quantify potential risk factors for early and late treatment failure
      in such infections. A retrospective review of 75 renal suppurative infections, at
      three tertiary Serbian Clinics of Urology, was conducted. We considered numerous
      potential risk factors in a multivariate analysis. This series was comprised of
      49 women and 26 men, with mean age of 56.7 years. There were 38 and 37 patients
      who experienced successful and unfavorable early treatment outcome, respectively.
      Overall mortality rate was 9.3%. Comorbidity [odds ratio (OR) = 1.6], complex
      suppurative pathological findings (OR = 3.6), presence of Pseudomonas spp. (OR =
      6.7), multiple bacterial strains (OR = 2.7), and positive culture itself (OR =
      3.6) were the predictors of poor early prognosis. A urological intervention and
      presence of pyonephrosis significantly increased the chance for good initial
      outcome (OR = 0.32 and 0.37, respectively). In the late treatment failure
      analysis presence of comorbidities (OR = 5.8) and treatment complications (OR =
      7.5) significantly increased chance for fatal outcome. Patients' baseline health
      status and complexity of suppuration itself were the most important predictors of
      clinical outcomes. Surgical drainage dominated over antimicrobial therapy.

PMID- 18709439
TI  - Iatrogenic pseudoaneurysm of the brachiocephalic artery: a rare complication of
      Hickman line insertion.
AB  - Central venous catheterization is widely used for hemodialysis for patients with
      renal failure. A number of short and long-term complications have been reported
      in literature. We describe a rare case of a lethal iatrogenic injury of the
      brachiocephalic artery (BA) in a 65-year-old woman following subclavian venous
      catheterization with a Hickman catheter. Contrast-enhanced CT-scan and
      reconstruction images demonstrated a pseudoaneurysm of the BA. Due to clinical
      deterioration, the patient underwent urgent sternotomy. Aspects concerning
      prevention and diagnosis of the above complication are analyzed.

PMID- 18709440
TI  - D1-protein dynamics in photosystem II: the lingering enigma.
AB  - The D1/D2 heterodimer core is the heart of the photosystem II reaction center. A
      characteristic feature of this heterodimer is the differentially rapid, light
      dependent degradation of the D1 protein. The D1 protein is possibly the most
      researched photosynthetic polypeptide, with aspects of structure-function, gene,
      messenger and protein regulation, electron transport, reactive oxygen species,
      photoinhibition, herbicide binding, stromal-granal translocations, reversible
      phosphorylation, and specific proteases, all under intensive investigation more
      than three decades after the protein's debut in the literature. This review will
      touch on some treaded areas of D1 research that have, so far, defied clear
      resolution, as well as cutting edge research on mechanisms and consequences of D1
      protein degradation.

PMID- 18709441
TI  - Importance of a single disulfide bond for the PsbO protein of photosystem II:
      protein structure stability and soluble overexpression in Escherichia coli.
AB  - PsbO protein is an important constituent of the water-oxidizing complex, located
      on the lumenal side of photosystem II. We report here the efficient expression of
      the spinach PsbO in E. coli where the solubility depends entirely on the
      formation of the disulfide bond. The PsbO protein purified from a pET32 system
      that includes thioredoxin fusion is properly folded and functionally active. Urea
      unfolding experiments imply that the reduction of the single disulfide bridge
      decreases stability of the protein. Analysis of inter-residue contact density
      through the PsbO molecule shows that Cys51 is located in a cluster with high
      contact density. Reduction of the Cys28-Cys51 bond is proposed to perturb the
      packing interactions in this cluster and destabilize the protein as a whole.
      Taken together, our results give evidence that PsbO exists in solution as a
      compact highly ordered structure, provided that the disulfide bridge is not
      reduced.

PMID- 18709442
TI  - Towards understanding the functional difference between the two PsbO isoforms in
      Arabidopsis thaliana--insights from phenotypic analyses of psbo knockout mutants.
AB  - The extrinsic PsbO subunit of the water-oxidizing photosystem II (PSII) complex
      is represented by two isoforms in Arabidopsis thaliana, namely PsbO1 and PsbO2.
      Recent analyses of psbo1 and psbo2 knockout mutants have brought insights into
      their roles in photosynthesis and light stress. Here we analyzed the two psbo
      mutants in terms of PsbOs expression pattern, organization of PSII complexes and
      GTPase activity. Both PsbOs are present in wild-type plants, and their expression
      is mutually controlled in the mutants. Almost all PSII complexes are in the
      monomeric form not only in the psbo1 but also in the psbo2 mutant grown under
      high-light conditions. This results either from an enhanced susceptibility of
      PSII to photoinactivation or from malfunction of the repair cycle. Notably, the
      psbo1 mutant displays such problems even under growth-light conditions. These
      results together with the finding that PsbO2 has a threefold higher GTPase
      activity than PsbO1 have significance for the turnover of the PSII D1 subunit in
      Arabidopsis.

PMID- 18709444
TI  - Abstracts of the 8th International Symposium on von Hippel-Lindau Disease.
      September 4-6, 2008. Roskilde, Denmark.

PMID- 18709443
TI  - Structure of an acetyl-CoA binding protein from Staphylococcus aureus
      representing a novel subfamily of GCN5-related N-acetyltransferase-like proteins.
AB  - We have determined the solution NMR structure of SACOL2532, a putative GCN5-like
      N-acetyltransferase (GNAT) from Staphylococcus aureus. SACOL2532 was shown to
      bind both CoA and acetyl-CoA, and structures with and without bound CoA were
      determined. Based on analysis of the structure and sequence, a subfamily of small
      GCN5-related N-acetyltransferase (GNAT)-like proteins can be defined. Proteins
      from this subfamily, which is largely congruent with COG2388, are characterized
      by a cysteine residue in the acetyl-CoA binding site near the acetyl group, by
      their small size in relation to other GNATs, by a lack of obvious substrate
      binding site, and by a distinct conformation of bound CoA in relation to other
      GNATs. Subfamily members are found in many bacterial and eukaryotic genomes, and
      in some archaeal genomes. Whereas other GNATs transfer the acetyl group of acetyl
      CoA directly to an aliphatic amine, the presence of the conserved cysteine
      residue suggests that proteins in the COG2388 GNAT-subfamily transfer an acetyl
      group from acetyl-CoA to one or more presently unidentified aliphatic amines via
      an acetyl (cysteine) enzyme intermediate. The apparent absence of a substrate
      binding region suggests that the substrate is a macromolecule, such as another
      protein, or that a second protein subunit providing a substrate-binding region
      must combine with SACOL2532 to make a fully functional N-acetyl transferase.

PMID- 18709445
TI  - Antibacterial protection of suture material by chlorhexidine-functionalized
      polyelectrolyte multilayer films.
AB  - The formation of bacterial biofilms on the surface of implanted materials is a
      critical factor that may lead to chronic microbial infection and tissue necrosis.
      In the present study we analysed the stability of polyelectrolyte multilayer (ML)
      films on suture materials and the antibacterial effect obtained with
      chlorhexidine (CHX)-functionalized films built on different types of suture
      materials such as silk, polyester and copolymer of glycolide and L: -lactide. The
      comparison of Escherichia coli culture on glass coverslips and glass coverslips
      with ML and CHX showed at 24 h an inhibition of the bacterial relative
      luminescence (40.68%, P < 0.5) and at 48 h (99.46%, P < 0.001). In another way,
      simple soaking of suture material overnight in CHX digluconate 20% without
      polyelectrolyte films did not at all protect sutures from bacterial colonization
      but CHX-functionalized polyelectrolyte films, made from poly-L: -glutamic acid
      and poly-L: -lysine, inhibited Escherichia coli proliferation.

PMID- 18709446
TI  - Investigation of carbon nanofibers as support for bioactive substances.
AB  - In this paper we have studied the adsorption properties of various bio-active
      systems onto the surface of carbon nanofibers (CNF) synthesized by chemical vapor
      deposition (CVD). Amino acids (alanine, aspartic acid, glutamic acid) and glucose
      oxidase (GOx) were adsorbed on CNF and the results were compared with those
      obtained when activated carbon (AC) was used as support. CNF and AC properties
      (hydrophilic or hydrophobic properties) were characterized by the pH value, the
      concentration of acidic/basic sites and by naphthalene adsorption. CNF with
      immobilized GOx was additionally investigated as a highly sensitive glucose
      biosensor. An amperometric method was used in an original manner to detect the
      changes in the specific activity of GOx, immobilized longer time on CNF. The
      method demonstrates that not the whole enzyme adsorbed onto CNF can catalyze the
      oxidation of glucose from the solution.

PMID- 18709447
TI  - Preparation of BMP-2 containing bovine serum albumin (BSA) nanoparticles
      stabilized by polymer coating.
AB  - PURPOSE: The purpose of this study was to investigate the preparation process of
      bone morphogenetic protein-2 (BMP-2) containing bovine serum albumin (BSA)
      nanoparticles (NPs), and to assess the bioactivity of BMP-2 encapsulated in such
      NPs. METHODS: The NPs were prepared by a coacervation method, and the effects of
      process parameters on NP size and polydispersity were examined. Polymer coated
      NPs were characterized with respect to amount of adsorbed polymer, particle size
      and zeta potential. Using bone marrow stromal cells (BMSC), biocompatibility of
      the NPs was investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) Assay, and bioactivity of the encapsulated BMP-2 was
      investigated by alkaline phosphatase (ALP) induction and calcification. RESULTS:
      The size of NPs could be controlled in the 50-400 nm range by process parameters
      including BSA concentration, non-solvent:solvent ratio and pH value. After
      coating with cationic polymers, the particle size and zeta potential were
      significantly increased. MTT assay indicated no toxicity of both the uncoated and
      coated NPs on BMSC. Based on ALP induction and calcification, full retention of
      BMP-2 bioactivity was retained in the polymer-coated NPs. CONCLUSIONS: This study
      described a preparation procedure for BSA NPs with controllable particle size,
      and such polymer-coated BSA NPs are promising delivery agents for local and
      systemic administration of BMP-2 in bone regeneration.

PMID- 18709448
TI  - Flocculated amorphous nanoparticles for highly supersaturated solutions.
AB  - PURPOSE: To recover polymer-stabilized amorphous nanoparticles from aqueous
      dispersions efficiently by salt flocculation and to show that the particles
      redisperse and dissolve rapidly to produce highly supersaturated solutions.
      METHODS: Nanoparticle dispersions of itraconazole stabilized by nonionic polymers
      were formed by antisolvent precipitation and immediately flocculated with sodium
      sulfate, filtered and dried. The size after redispersion in water, crystallinity,
      and morphology were compared with those for particles produced by spray drying
      and rapid freezing. RESULTS: Particle drug loading increased to approximately 90%
      after salt flocculation and removal of excess polymer with the filtrate. The
      formation of the flocs at constant particle volume fraction led to low fractal
      dimensions (open flocs), which facilitated redispersion in water to the original
      primary particle size of approximately 300 nm. Amorphous particles, which were
      preserved throughout the flocculation-filtration-drying process, dissolved to
      supersaturation levels of up to 14 in pH 6.8 media. In contrast, both spray dried
      and rapidly frozen nanoparticle dispersions crystallized and did not produce
      submicron particle dispersions upon addition to water, nor high supersaturation
      values. CONCLUSIONS: Salt flocculation produces large yields of high surface area
      amorphous nanoparticle powders that de-aggregate and dissolve rapidly upon
      redispersion in pH 6.8 media, for supersaturation levels up to 14.

PMID- 18709450
TI  - Photoluminescence enhancement effect of CeO2 in rare earth composites MM'O3/CeO2
      and MM'O3/CeO2: Pr(3+) (M = Ca, Sr; M' = Ti, Zr).
AB  - In the context, a modified sol-gel technology was afford to the synthesis of rare
      earth composite ceramic phosphors MM'O(3)/CeO(2) and MM'O(3)/CeO(2): Pr(3+) (M =
      Ca, Sr; M' = Ti, Zr) with multicomponent hybrid precursors were composed. The
      micromorphology, particle size and photoluminescence properties were studied with
      XRD, SEM and luminescent spectroscopy in detail. Both XRD and SEM indicated the
      particle sizes were in the submicrometer range of 100-300 nm. The
      photoluminescence for these ceramic phosphors were studied in details with the
      different component of host (molecular ratio of Sr, Ca and Ti, Zr), presenting a
      broad spectral band in the visible blue-violet region with the maximum excitation
      peak at 449 nm and a wide emission range with a maximum peak at 619 nm, which was
      ascribed to be the characteristic transition of Pr(3+) ((1)D(2) --> (3)H(4)).
      These phosphors can be expected for visible light conversion (blue --> red)
      materials. Especially it can be found that the introduction of CeO(2) can enhance
      the luminescence intensity of MM'O(3) and MM'O(3): Pr(3+).

PMID- 18709449
TI  - Common integration sites for MMTV in viral induced mouse mammary tumors.
AB  - The paradigm of mammary cancer induction by the mouse mammary tumor virus (MMTV)
      is used to illustrate the body of evidence that supports the hypothesis that
      mammary epithelial stem/progenitor cells represent targets for oncogenic
      transformation. It is argued that this is not a special case applicable only to
      MMTV-induced mammary cancer, because MMTV acts as an environmental mutagen
      producing random interruptions in the somatic DNA of infected cells by insertion
      of proviral DNA copies. In addition to disrupting the host genome, the proviral
      DNA also influences gene expression through its associated enhancer sequences
      over significant inter-genomic distances. Genes commonly affected by MMTV
      insertion in multiple individual tumors include, the Wnt, FGF, RSpo gene families
      as well as eIF3e and Notch4. All of these gene families are known to play
      essential roles in stem cell maintenance and behavior in a variety of organs. The
      MMTV-induced mutations accumulate in cells that are long-lived and possess the
      properties of stem cells, namely, self-renewal and the capacity to produce
      divergent epithelial progeny through asymmetric division. The evidence shows that
      epithelial cells with these properties are present in normal mammary glands, may
      be infected with MMTV, become transformed to produce epithelial hyperplasia
      through MMTV-induced mutagenesis and progress to frank mammary malignancy.
      Retroviral marking via MMTV proviral insertion demonstrates that this process
      progresses from a single mammary epithelial cell that possesses all of the
      features ascribed to tissue-specific stem cells.

PMID- 18709451
TI  - The clinical spectrum of leukocyte adhesion deficiency (LAD) III due to defective
      CalDAG-GEF1.
AB  - INTRODUCTION: Leukocyte adhesion deficiency (LAD) type III is a rare syndrome
      characterized by severe recurrent infections, leukocytosis, and increased
      bleeding tendency. All integrins are normally expressed yet a defect in their
      activation leads to the observed clinical manifestations. MATERIALS AND METHODS:
      Less than 20 patients have been reported world wide and the primary genetic
      defect was identified in some of them. Here we describe the clinical features of
      patients in whom a mutation in the calcium and diacylglycerol-regulated guanine
      nucleotide exchange factor 1 (CalDAG GEF1) was found and compare them to other
      cases of LAD III and to animal models harboring a mutation in the CalDAG GEF1
      gene. DISCUSSION: The hallmarks of the syndrome are recurrent infections
      accompanied by severe bleeding episodes distinguished by osteopetrosis like bone
      abnormalities and neurodevelopmental defects.

PMID- 18709452
TI  - HIV-infected prison inmates: depression and implications for release back to
      communities.
AB  - High rates of both HIV and depression are seen in prison populations; depression
      has been linked to disease progression in HIV, risky behaviors, and medication
      non-adherence. Despite this, few studies have examined HIV-infected inmates with
      depression. We therefore conducted an exploratory study of a sample of HIV
      infected inmates in North Carolina prisons (N = 101) to determine what proportion
      of this sample screened positive for depression and whether depression was
      associated with different pre-incarceration characteristics or post-release
      needs. A high proportion of HIV infected inmates (44.5%) screened positive for
      depression. Depressed inmates were significantly more likely have low coping self
      efficacy scores (180 vs. 214), to report having had resource needs (OR = 2.91)
      prior to incarceration and to anticipate needing income (OR = 2.81), housing (OR
      = 4.07), transportation (OR = 9.15), and assistance with adherence (OR = 8.67)
      post-release. We conclude by discussion the implications of our findings for
      prison based care and effective prison release planning for HIV infected inmates.

PMID- 18709454
TI  - Genetic analysis of interleukin-1A C(-889)T polymorphism with Alzheimer disease.
AB  - Neuroinflammation has been implicated in the etiology of Alzheimer's disease
      (AD). Many studies have suggested that C(-889) T promoter polymorphism in one of
      the proinflammatory cytokine interleukin-1 (IL-1) encoding gene IL-1A may be
      associated with AD pathogenesis. To determine whether the polymorphism
      contributes to the risk for late-onset AD (LOAD) in Chinese, we carried out our
      investigation in 344 sporadic LOAD patients and 224 healthy controls. No
      statistical significant association was obtained between IL-1A C(-889) T
      polymorphism and LOAD and no statistical difference was found between cases and
      controls after stratification for apolipoprotein E allele 4 (APOE epsilon4)
      status. The results reveal that it is not likely that the IL-1A C(-889) T
      polymorphism is involved in AD pathogenesis in the Chinese population. Further
      studies of the associations between other IL-1A genetic polymorphisms and AD
      should be performed in a larger population and biologic functional analysis of IL
      1A gene is required to verify the underlying roles of IL-IA in LOAD.

PMID- 18709455
TI  - Di-tert-butylsilylene-directed alpha-selective synthesis of p-nitrophenyl T
      antigen analogues.
AB  - Seven analogues of p-nitrophenyl T-antigen [Galbeta(1-->3)GalNAcalpha(1-->O)PNP]
      have been synthesized as potential substrates for elucidation of the substrate
      specificity of endo-alpha-N-acetylgalactosaminidase. These compounds, which are
      commercially unavailable, include: GlcNAcbeta(1-->3){GlcNAcbeta(1-
      >6)}GalNAcalpha(1-->O)PNP [core 4 type], GalNAcalpha(1-->3)GalNAcalpha(1-->O)PNP
      [core 5 type], GlcNAcbeta(1-->6)GalNAcalpha(1-->O)PNP [core 6 type],
      GalNAcalpha(1-->6)GalNAcalpha(1-->O)PNP [core 7 type], Galalpha(1-
      >3)GalNAcalpha(1-->O)PNP [core 8 type], Glcbeta(1-->3)GalNAcalpha(1-->O)PNP and
      GalNAcbeta(1-->3)GalNAcalpha(1-->O)PNP. The assembly of these synthetic probes
      was accomplished efficiently, based on di-tert-butylsilylene(DTBS)-directed alpha
      galactosylation as a key reaction.

PMID- 18709453
TI  - Depressive symptoms, utilization of mental health care, substance use and sexual
      risk among young men who have sex with men in EXPLORE: implications for age
      specific interventions.
AB  - The EXPLORE study evaluated a behavioral intervention to prevent HIV infection
      among MSM. We examined depressive symptoms, utilization of mental health care,
      substance use and HIV risk taking behaviors in YMSM aged 16-25 years compared
      with their older counterparts. YMSM were more likely to report depressive
      symptoms (OR = 1.55) and less likely to report use of counseling (OR = 0.39) or
      medication (OR = 0.20) for psychiatric conditions. YMSM were more likely to
      report heavy alcohol and drug use. YMSM more often reported engaging in
      unprotected insertive (OR = 1.60) and receptive (OR = 2.07) anal intercourse with
      presumed HIV-uninfected partners, and unprotected receptive (OR = 1.72) anal
      intercourse with partners of unknown-HIV status. These findings suggest the need
      for more appropriate and accessible mental health care and substance use services
      for YMSM. Additionally, HIV prevention work with this population should provide
      comprehensive education about HIV testing and risk reduction counseling that
      focuses on communication about serostatus and safety in sexual situations.

PMID- 18709456
TI  - Household density among undocumented Mexican immigrants in New York City.
AB  - BACKGROUND: High household density increases exposure to communicable diseases,
      psychological distress in adults, and poor long-term health in children. High
      residential density, which may be a mediator of poor health, is common among
      immigrants. METHODS: We used data from a pilot survey among Mexican immigrants in
      New York City. Respondents were recruited through venue-based sampling in
      neighborhoods with large Mexican populations. RESULTS: Among respondents that
      reported being undocumented (N = 404), the mean number of people per room (PPR)
      of residence was 2.2. In multivariate analyses, living in conditions of >2 PPR
      was positively associated with living with one's children (OR = 2.3, 95% CI = 1.4
      3.9), having experienced food insecurity in the past 6 months (OR = 2.0, 95% CI =
      1.1-3.6), and language discrimination (OR = 2.3 compared to other forms of
      discrimination, 95% CI = 1.2-4.4). CONCLUSIONS: Undocumented Mexican immigrants,
      particularly those who are linguistically marginalized and experience food
      insufficiency, live in conditions of marked household density in NYC.

PMID- 18709458
TI  - Morphological assessment of the cerebroprotective action of lanthanum acetate in
      chronic cerebral ischemia in rats.
AB  - The aim of the present work was to perform a morphological assessment of the
      cerebroprotective action of lanthanum acetate in chronic cerebral ischemia in
      rats. Chronic ischemia was produced in Wistar rats (weighing 160-180 g) by
      ligation of both common carotid arteries. Ischemic lesions were corrected by
      intragastric lanthanum acetate (3 mg/kg per day) throughout the experimental
      period. Ischemic damage to the cortex was assessed morphometrically on
      histological sections stained by the Nissl method. Lanthanum acetate was found to
      suppress the development of ischemic neuron damage in the cerebral cortex, with
      reductions in the numbers of hyperchromic neurons, cells with focal
      chromatolysis, and ghost cells, as well as an increase in the number of
      normochromic cells as compared with controls.

PMID- 18709459
TI  - Projections of the basal ganglia to the zona incerta of the dog diencephalon.
AB  - Retrograde axonal transport of horseradish peroxidase was used to show that the
      projections of the globus pallidus, entopeduncular nucleus, substantia nigra, and
      pedunculopontine tegmental nucleus in dogs are directed to all segments of the
      zone incerta. The experiments reported here identified no topical features in the
      organization of these projections in dogs, as application of marker to different
      areas of the zona incerta yielded similar distributions of labeled neurons in the
      basal ganglia. No striatal projections to the zone incerta were found.

PMID- 18709457
TI  - Mechanisms of disease: the oxidative stress theory of diabetic neuropathy.
AB  - Diabetic neuropathy is the most common complication of diabetes, affecting 50% of
      diabetic patients. Currently, the only treatment for diabetic neuropathy is
      glucose control and careful foot care. In this review, we discuss the idea that
      excess glucose overloads the electron transport chain, leading to the production
      of superoxides and subsequent mitochondrial and cytosolic oxidative stress.
      Defects in metabolic and vascular pathways intersect with oxidative stress to
      produce the onset and progression of nerve injury present in diabetic neuropathy.
      These pathways include the production of advanced glycation end products,
      alterations in the sorbitol, hexosamine and protein kinase C pathways and
      activation of poly-ADP ribose polymerase. New bioinformatics approaches can
      augment current research and lead to new discoveries to understand the
      pathogenesis of diabetic neuropathy and to identify more effective molecular
      therapeutic targets.

PMID- 18709460
TI  - The possible use of hypoxic preconditioning for the prophylaxis of post-stress
      depressive episodes.
AB  - The protective effects of hypoxic preconditioning on the development of
      depressive states in rat models were studied. Three episodes of intermittent
      preconditioning using hypobaric hypoxia (360 mmHg, 2 h) prevented the onset of
      depressive behavioral reactions, hyperfunction of the hypophyseal-adrenal system,
      and impairments in its suppression in the dexamethasone test in rats following
      unavoidable aversive stress in a model of endogenous depression. The anxiolytic
      and antidepressant actions of hypoxic preconditioning in experiments on rats were
      no less marked than those of the tetracyclic antidepressant ludiomil. The results
      obtained here provide evidence that preconditioning with intermittent hypobaric
      hypoxia increases resistance to psychoemotional stresses, has marked anxiolytic
      and antidepressant effects, and can be used for the prophylaxis of depressive
      episodes.

PMID- 18709461
TI  - Individual variability in the structural asymmetry of the dorsomedial nucleus of
      the thalamus in men and women.
AB  - Quantitative neurohistochemical parameters were used to study the structure of
      the dorsomedial nucleus of the thalamus. The study set consisted of 10 specimens
      from the collection of the Institute of the Brain, Russian Academy of Medical
      Sciences and included seven men and three women aged 19-59 years, all right
      handed, who died suddenly and had no neurological or mental diseases during life.
      The following parameters were measured: neuron density, total and satellite glia
      densities, the density of satellite-surrounded neurons, and the ratios of
      satellite glia to all glia and neurons surrounded by satellite glia to all
      neurons. On a background of individual variability in these measures, a number of
      gender-related and interhemisphere differences were found. Thus, neuron density
      in both men and women showed no asymmetry and individual variability was less
      marked in women. Glial cell density in men was greater on the right, while in
      women it was greater on the left; satellite glial cell density, conversely, was
      greater on the left in men and more variable in women. Significant asymmetry with
      greater values on the left in men was seen for the density of neurons surrounded
      by satellite glia, while this was more variable in women, though the ratio of
      neurons with satellite glia to all neurons was greater on the left in men and
      women, as was the ratio of satellite glia to all glial cells. Overall, there was
      a tendency to rather greater asymmetry in this structure in men and a tendency to
      greater individual variability in women.

PMID- 18709462
TI  - Cognitive functions and the state of nonspecific brain systems in panic
      disorders.
AB  - A total of 93 patients with panic disorders and 36 healthy control subjects were
      studied. Clinical-neurological, psychometric, neuropsychological, and
      neurophysiological (auditory cognitive evoked potentials) investigations were
      performed. Patients with typical panic disorders were characterized by increased
      levels of anxiety and depression, along with impairments to cognitive functions
      in the form of decreases in short-term memory and attention, as compared with
      healthy subjects. Patients with atypical panic disorders differed from patients
      with typical panic disorders in having lower levels of anxiety, more severe
      depression, and more marked cognitive disorders. As compared with healthy
      subjects, patients with atypical panic disorders showed reductions in the
      amplitude of the P300 evoked potential wave, while patients with typical panic
      disorders showed increases. It is suggested that changes in the amplitude
      parameters of the P300 wave are associated with dysfunction of the limbic
      reticular structures of the brain in patients with panic disorders.

PMID- 18709463
TI  - Isolated neurons as biosensors responding to the release of neuroactive
      substances.

PMID- 18709464
TI  - Serotonin and NMDA glutamate receptor antagonists selectively impair the
      reactivation of associative memory in the common snail.
AB  - Experiments on the common snail were performed to study the influences of
      serotonin and glutamate receptor antagonists on the processes of reactivation of
      an associative habit consisting of refusing a particular type of food. Twenty
      four hours after training, animals were injected with the non-selective serotonin
      receptor antagonist methiothepin (0.1 mg/snail) or the NMDA glutamate receptor
      antagonist MK-801 (0.005 mg/snail), after which they were presented with a
      "reminder" stimulus (the "conditioned reflex" foodstuff, a banana) and tested for
      retention of the habit. Three hours after antagonist injections and the
      "reminding" procedure, snails showed impairments in the reproduction of the
      acquired habit, which persisted for more than two weeks. Furthermore, animals
      with amnesia after treatment with methiothepin/reminding showed facilitation of
      repeated acquisition of the aversive habit to banana. Repeat training of animals
      which had shown amnesia after MK-801/reminding did not result in acquisition of
      the habit. It is suggested that serotonin receptors are involved in the
      mechanisms underlying extraction of the memory trace of the aversive habit to the
      foodstuff in snails, while NMDA glutamate receptors are involved in memory trace
      storage processes.

PMID- 18709465
TI  - Neuronal connections of eye-dominance columns in the cat cerebral cortex after
      monocular deprivation.
AB  - Plastic changes in intrahemisphere neuronal connections of the eye-dominance
      columns of cortical fields 17 and 18 were studied in monocularly deprived cats.
      The methodology consisted of microintophoretic administration of horseradish
      peroxidase into cortical columns and three-dimensional reconstruction of the
      areas of retrograde labeled cells. The eye dominance of columns was established,
      as were their coordinates in the projection of the visual field. In field 17, the
      horizontal connections of columns receiving inputs from the non-deprived eye via
      the crossed-over visual tracts were longer than the connections of the "non
      crossed" columns of this eye and were longer than in normal conditions; the
      connections of the columns of the deprived eye were significantly reduced.
      Changes in the spatial organization of horizontal connections in field 17 were
      seen for the columns of the non-deprived eye (areas of labeled cells were rounder
      and the density of labeled cells in these areas were non-uniform). The longest
      horizontal connections in deprived cats were no longer than the lengths of these
      connections in cats with strabismus. It is suggested that the axon length of
      cells giving rise to the horizontal connections of cortical columns has a limit
      which is independent of visual stimulation during the critical period of
      development of the visual system.

PMID- 18709466
TI  - Characteristics of visual seeking and evoked potentials in the extrastriate areas
      of the cortex in humans.
AB  - Studies in 11 young, healthy subjects addressed the characteristics of visual
      seeking (time taken, errors) on changes in the parameters of the target element
      to be sought (shape, color, and location) in an environment containing
      heterogeneous white distractors. Evoked potentials (EP) were recorded in six
      cortical leads (P3, P4, T3, T4, T5, T6) and the late endogenous components of EP
      were studied, i.e., the N2 and P3 components (standard terminology), as these
      components are known to change when the type of search changes, in the zone of so
      called late selection. When the search difficulty increased (increased similarity
      between target and distractors), an increase in seeking time was accompanied by a
      delay in the P3 component and a decrease in its amplitude. Location of the target
      in a defined position resulted in a decrease in search time and a reduction in
      the latent period of the P3 component as compared with the situation in which the
      target position was indeterminate. Changes in the color of the target stimulus
      led to elimination of the inhibitory action of the distractors: EP parameters
      were no different from those recorded on presentation of single stimuli. A high
      level of correlation was found between search parameters and measures of the P3
      component. Changes in EP in different types of search were essentially identical
      (no statistical differences) in the parietal and temporal leads. This suggests
      that on seeking the target in the environment, the parietal and temporal areas of
      the cortex function as a single system.

PMID- 18709467
TI  - Interaction of hypocapnia, hypoxia, brain blood flow, and brain electrical
      activity in voluntary hyperventilation in humans.
AB  - Changes in various physiological measures in voluntary hyperventilation lasting
      three minutes or more in humans were studied and compared. Three-minute
      hyperventilation, in which the rate of external ventilation increased by an
      average factor of 4.5-5, produced similar phasic changes in central and brain
      hemodynamics. The rate of circulation, indicated by rheographic data, initially
      increased during hyperventilation, reaching a maximum at 1-2 min of the test;
      there was then a reduction, to a minimum 2-3 min after the end of the test; this
      was followed by a further slow increase. The rate of cerebral blood flow during
      all 3 min of hyperventilation remained elevated in most subjects as compared with
      baseline and decreased during the 5 min following the end of the test.
      Transcutaneous carbon dioxide tension changed differently - there was a decrease
      to a minimum (about 25 mmHg) by the end of the test, lasting 1 min from the end
      of the test, this being followed by an increase to a level of 90% of baseline at
      5 min after the test. Blood oxygen saturation remained at 98-100% during the
      test, decreasing to about 90% 5 min after the test; this, along with the decrease
      in cerebral blood flow, was a factor producing brain hypoxia. In different
      subjects, changes in the spectral power of oscillations in different EEG ranges
      on hyperventilation were "mirrored" to different extents by the dynamics of
      transcutaneous carbon dioxide tension. The duration and repetition of
      hyperventilation were important factors for understanding the interaction between
      brain hemodynamics, hypocapnia, hypoxia, and brain electrical activity. After
      several repetitions of 3-min hyperventilation over a period of 1 h, the
      increasing brain blood flow could decrease significantly on the background of
      relatively small changes in brain electrical activity. The data presented here
      were assessed from the point of view of the important role of brain tissue oxygen
      utilization mechanisms in adaptation to hypoxia and hypocapnia.

PMID- 18709469
TI  - Greater than age-related changes in brain diffusion of HIV patients after 1 year.
AB  - Chronic infection with HIV is associated with neuroinflammation. Prior diffusion
      tensor imaging (DTI) studies demonstrated increased mean diffusion (MD) and
      decreased fractional anisotropy (FA) in the white matter (WM) and subcortical
      brain regions of HIV patients. The current study aims to detect whether there are
      greater than age-related brain changes in HIV patients after a 1-year follow-up
      period using DTI. Thirty-nine antiretroviral-stable HIV subjects and 32 HIV
      seronegative (SN) controls were evaluated, with neuropsychological tests and DTI,
      at baseline and after 1 year. MD and FA in the genu and splenium of the corpus
      callosum and in six other subcortical and white matter regions were evaluated
      bilaterally. Compared to SN controls, HIV subjects had significantly higher MD in
      the frontal WM (p = 0.0104) and lower FA in the parietal WM (p = 0.006). After 1
      year, HIV subjects showed increase in MD in frontal and parietal WM, putamen, and
      genu; HIV subjects also showed greater increased genu diffusion than SN controls
      (p = 0.005). Changes in global cognitive deficit score correlated with changes in
      MD in the genu and FA in the parietal and frontal WM and putamen (multiple
      regression, p = 0.0008). Lastly, normal age-dependent changes in frontal WM
      diffusion and FA in genu and putamen were not observed in HIV subjects. Since
      increased MD may reflect increased neuroinflammation, our findings suggest
      greater than normal age-related inflammatory changes in the genu of these HIV
      patients, which may contribute to the cognitive deficits. Measurements of MD in
      the genu may be useful for monitoring disease progression in HIV brain infection.

PMID- 18709468
TI  - The role of oxidative stress, metabolic compromise, and inflammation in neuronal
      injury produced by amphetamine-related drugs of abuse.
AB  - Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are
      amphetamine derivatives with high abuse liability. These amphetamine-related
      drugs of abuse mediate their effects through the acute activation of both
      dopaminergic and serotonergic neurons. Long-term abuse of these amphetamine
      derivatives, however, results in damage to both dopaminergic and serotonergic
      terminals throughout the brain. This toxicity is mediated in part by oxidative
      stress, metabolic compromise, and inflammation. The overall objective of this
      review is to highlight experimental evidence that METH and MDMA increase
      oxidative stress, produce mitochondrial dysfunction, and increase inflammation
      that converge and culminate in the long-term toxicity to dopaminergic and
      serotonergic neurons.

PMID- 18709471
TI  - Diversity in current ecological thinking: implications for environmental
      management.
AB  - Current ecological thinking emphasizes that systems are complex, dynamic, and
      unpredictable across space and time. What is the diversity in interpretation of
      these ideas among today's ecologists, and what does this mean for environmental
      management? This study used a Policy Delphi survey of ecologists to explore their
      perspectives on a number of current topics in ecology. The results showed general
      concurrence with nonequilibrium views. There was agreement that disturbance is a
      widespread, normal feature of ecosystems with historically contingent responses.
      The importance of recognizing multiple levels of organization and the role of
      functional diversity in environmental change were also widely acknowledged. Views
      differed regarding the predictability of successional development, whether
      "patchiness" is a useful concept, and the benefits of shifting the focus from
      species to ecosystem processes. Because of their centrality to environmental
      management, these different views warrant special attention from both managers
      and ecologists. Such divergence is particularly problematic given widespread
      concerns regarding the poor linkages between science (here, ecology) and
      environmental policy and management, which have been attributed to scientific
      uncertainty and a lack of consensus among scientists, both jeopardizing the
      transfer of science into management. Several suggestions to help managers deal
      with these differences are provided, especially the need to interpret broader
      theory in the context of place-based assessments. The uncertainty created by
      these differences requires a proactive approach to environmental management,
      including clearly identifying environmental objectives, careful experimental
      design, and effective monitoring.

PMID- 18709470
TI  - Mesothelioma epidemiology, carcinogenesis, and pathogenesis.
AB  - OPINION STATEMENT: The incidence of mesothelioma has gone from almost none to the
      current 2500-3000 cases per year in the USA. This estimate is an extrapolation
      based on information available from the Surveillance, Epidemiology and End
      Results (SEER) Program that collects information on approximately 12% of the US
      population. Mesothelioma is a cancer that is linked to exposure to carcinogenic
      mineral fibers. Asbestos and erionite have a proven causative role; the possible
      role of other mineral fibers in causing mesothelioma is being investigated.
      Asbestos is considered the main cause of mesothelioma in the US and in the
      Western world. The capacity of asbestos to induce mesothelioma has been linked to
      its ability to cause the release of TNF-alpha (that promotes mesothelial cells
      survival), other cytokines and growth factors, and of mutagenic oxygen radicals
      from exposed mesothelial cells and nearby macrophages. Some investigators
      proposed that as a consequence of the regulations to prevent exposure and to
      forbid and/or limit the use of asbestos, the incidence of mesothelioma in the US
      (and in some European countries) should have started to decline before or around
      the year 2000, and sharply decline thereafter. Unfortunately, there are no data
      available yet to support this optimistic hypothesis. Simian virus 40 (SV40)
      infection and radiation exposure are additional causes, although their
      contribution to the overall incidence of mesothelioma is unknown. Recent data
      from several laboratories indicate that asbestos exposure and SV40 infection are
      co-carcinogens in causing mesothelioma in rodents and in causing malignant
      transformation of human mesothelial cells in tissue culture. An exciting new
      development comes from the discovery that genetic susceptibility to mineral fiber
      carcinogenesis plays a critical role in the incidence of this cancer in certain
      families. It is hoped that the identification of this putative mesothelioma gene
      will lead to novel mechanistically driven preventive and therapeutic approaches.

PMID- 18709472
TI  - Dietary folate intake during pregnancy and birth weight in Japan.
AB  - BACKGROUND: Inadequate folate status has been associated with many negative
      reproductive outcomes, such as neural tube defects (NTD), low birth weight and
      placental abruption. AIM OF THE STUDY: The objectives of this study were to
      evaluate the levels of dietary folate intake during pregnancy in Japanese women
      and the subsequent birth weight of their babies. METHODS: A longitudinal
      prospective study was conducted with 197 women with a singleton pregnancy in
      2005. Dietary folate was investigated 3 times: in the first trimester at 12
      weeks, in the second trimester at 20 weeks and in third trimester at 32 weeks
      using a diet history questionnaire (DHQ). Non fasting blood samples were
      collected from the women for measurement of homocysteine, hemoglobin, ferritin,
      unbound iron-binding capacity (UIBC) and total iron-binding capacity (TIBC).
      RESULTS: Energy intake increased as pregnancy advanced, but not significantly.
      The daily intake of folate increased from 248.5 +/- 113.1 microg/d in the first
      trimester to 275.4 +/- 100.2 microg/d in the third trimester (P = 0.04). This was
      well below the recommended level of 440 microg/d and only 10% of mothers were
      above the levels. In the third trimester, plasma homocysteine concentration was
      significantly higher in the low folate group of less than 250 microg/d (P =
      0.02), but not the first and second trimesters. Dietary folate intake and plasma
      homocysteine concentrations were not likely to be predictors of birth weight in
      our subjects. CONCLUSIONS: Our study shows that Japanese women's energy and
      folate intakes do not meet their energy needs during pregnancy and are at an
      extremely low recommended dietary allowance level throughout pregnancy.

PMID- 18709474
TI  - Intracerebral haematoma at a microbleed site in two lacunar stroke patients on
      antithrombotic therapy.

PMID- 18709473
TI  - Low total plasma carotenoids are independent predictors of mortality among older
      persons: the InCHIANTI study.
AB  - BACKGROUND: Plasma carotenoids are considered a valid biological marker for fruit
      and vegetable dietary intake. Recent studies show that low carotenoid levels are
      associated with a high risk of inflammation, cancer, and cardiovascular disease.
      AIM OF THE STUDY: To determine whether low plasma carotenoids are associated with
      increased mortality among older adults. METHODS: Longitudinal study among 1,043
      adults, 65 years and older, in the InCHIANTI study, a population-based cohort of
      adults living in the community in the Tuscany region, Italy. RESULTS: Mean total
      carotenoid concentration was 1.80 micromol/l. During eight years of follow-up,
      310 (29.7%) of participants died. Eight-year survival was lower in the lowest
      compared with the highest tertile of total serum carotenoids (P < 0.0001 by
      Mantel-Haenszel chi-square). In a multivariate Cox proportional hazards model
      adjusted for age, education, smoking, body mass index, energy intake, and chronic
      diseases, adults in the highest tertile of plasma carotenoids at enrollment had
      lower mortality compared to those in the lowest tertile (Hazards Ratio obtained
      by considering carotenoids level as an ordinal variable 0.81, 95%; CI 0.65-0.99;
      P for trend = 0.046). CONCLUSIONS: Low plasma carotenoids are an independent risk
      factor for mortality among older adults living in the community.

PMID- 18709475
TI  - Characterization, expression and subcellular distribution of a novel MFP1 (matrix
      attachment region-binding filament-like protein 1) in onion.
AB  - MFP1 (matrix attachment region-binding filament-like protein 1) is a conserved
      nuclear and chloroplast DNA-binding protein encoded by a nuclear gene, well
      characterized in dicot species. In monocots, only a 90 kDa MFP1-related protein
      had been characterized in the nucleus and nuclear matrix of Allium cepa
      proliferating cells. We report here a novel MFP1-related nuclear protein of 80
      kDa in A. cepa roots, with M(r) and pI values similar to those of MFP1 proteins
      in dicot species, and which also displays a dual location, in the nucleus and
      chloroplasts of leaf cells. However, this novel protein is not a nuclear matrix
      component. It shows a spotted intranuclear distribution in small foci differing
      from the nuclear bodies containing the 90 kDa protein. In electron microscopy
      analysis, the intranuclear foci containing the 80 kDa MFP1 appeared as small
      loose structures at the periphery of condensed chromatin patches. This protein
      was also located in the nucleolus. It was abundant in meristematic cells, but its
      level fell when proliferation stopped. This different expression and
      distribution, and its preferential location at the boundaries between
      heterochromatin and euchromatin, suggest that the novel 80 kDa protein might be
      associated with decondensed DNA and could play a role in chromatin organization.

PMID- 18709476
TI  - Effect of cadmium on pollen germination and tube growth in Lilium longiflorum and
      Nicotiana tabacum.
AB  - Cadmium had a highly toxic effect on pollen germination and tube growth, which
      were greatly inhibited as metal concentrations increased. Cadmium concentrations
      up to 10(-2) M completely stopped pollen germination and pollen showed an
      increasing tendency to burst within 1 h. At low concentrations, the metal caused
      a slight stimulation of pollen germination, growth rate and tube elongation at
      the initial stages of tube development. Comparing the two plants studied, cadmium
      was more toxic for Nicotiana tabacum than for Lilium longiflorum pollen. Pollen
      tubes showed a range of strong morphological abnormalities, characterized by
      uneven or aberrant growth, including apical branching or swelling at the tip of
      the pollen tube. Cell wall intrusions at or near the tip were evident on the
      inner side, whereas a loose network formed from fibrillar material was observed
      on the outer layers. After prolonged cadmium exposure, round (ball-like)
      aggregates were embedded in a fine fibrillar network. Increased cadmium
      concentrations (10(-3)-10(-2) M) decreased or completely paralyzed cytoplasmic
      streaming. No typical cytoplasmic zonation existed, while cell organelles
      (plastids, lipid droplets) were relocated toward the tip. The vesicular apical
      zone was drastically reduced, with vesicles dispersed into the subapical region.
      Mitochondria were distributed throughout the subapical region and among the
      vesicles of the tube apex. Visible ultrastructural changes in cell organelles
      were not observed.

PMID- 18709477
TI  - The cytoplasmic domain of the cellulose-synthesizing complex in vascular plants.
AB  - The cytoplasmic domain of the rosette terminal complex has been imaged in situ in
      patches of plasma membrane isolated from tobacco BY-2 protoplasts. By partially
      extracting the plasma membrane lipids, cellulose microfibrils were observed
      through the plasma membrane. Rosette terminal complexes were identified on the
      basis of their association with the ends of these cellulose microfibrils. The
      cytoplasmic domain of the rosette terminal complex has been shown to be hexagonal
      in shape and has been measured to be 45-50 nm in diameter and 30-35 nm tall.
      These findings demonstrate that the terminal complex does indeed have a
      substantial cytoplasmic component, and that the hexagonal array observed in the
      lipid bilayer by freeze fracture is actually only a small part of the overall
      complex. These findings will allow better modeling of the terminal complex and
      may facilitate predictions of how many proteins are associated with the rosette
      terminal complex in vivo.

PMID- 18709478
TI  - Monozygotic female twins discordant for Silver-Russell syndrome and
      hypomethylation of the H19-DMR.
AB  - Silver-Russell syndrome (SRS) is characterized by growth failure and dysmorphic
      features, and is frequently caused by hypomethylation of the paternally derived
      H19-DMR (epimutation). We observed 5 8/12-year-old female twins discordant for
      SRS. One twin exhibited SRS-compatible features, such as pre- and postnatal
      growth failure, relative macrocephaly, triangular face, left hemihypotrophy, and
      bilateral fifth finger clinodactyly, whereas the other twin showed apparently
      normal phenotype. Microsatellite analysis for 26 loci on multiple chromosomes
      showed monozygosity. Methylation analysis for the H19-DMR indicated epimutation
      in roughly half of cells in the affected twin and normal patterns in the
      unaffected twin and the parents. X-inactivation analysis revealed random X
      inactivation with a nearly identical pattern between the twins. The discordant
      methylation pattern of the H19-DMR may primarily be due to a failure to maintain
      the DNA methyltransferase-1-dependent methylation imprint around the pre
      implantation S phase, because such failure would result in the production of two
      different cell clones, one with normally methylated DMR and the other with
      demethylated DMR, leading to the separation of cells with different characters
      and resultant twinning.

PMID- 18709479
TI  - Low-dose aspirin-induced gastrointestinal diseases: past, present, and future.
AB  - Meta-analyses of randomized, placebo-controlled trials of low-dose aspirin
      indicate that aspirin approximately doubles the risk of major GI bleeding
      compared with placebo. The risk in Japanese may possibly be higher compared to
      Western populations, although the evidence is still lacking and prospective
      studies are required. Prior GI events, older age, and use of other injurious
      medicines such as NSAIDs, anticoagulants, and corticosteroids seem to be factors
      associated with an increased risk for upper GI bleeding among aspirin users.
      Prospective studies are needed to identify specific risk factors for upper GI
      bleeding in Japanese patients taking low-dose aspirin. There are many potential
      gastroprotective drugs available in Japan, and studies are needed to assess the
      relative effectiveness of various strategies including PPI use for the prevention
      of aspirin-related upper GI ulcer complications and whether any of these other
      agents also provide protection against small bowel or colonic damage. Aspirin
      induced enteropathy is now increasingly being recognized and is presumably not
      uncommon, and the availability of new imaging techniques for the small intestine
      and noninvasive tests such as fecal calprotectin should allow rapid progress in
      this important area.

PMID- 18709481
TI  - Morphogenesis of a colorectal neoplasm with a type IIIS pit pattern inferred from
      isolated crypts.
AB  - BACKGROUND: The goal of this study was to clarify morphogenetic development in
      colorectal neoplasms with depressions by examining isolated crypts and their pit
      patterns. METHODS: Twelve colorectal neoplasms with depressions were examined
      endoscopically, stereomicroscopically, and histopathologically. The pit pattern
      was defined according to Kudo's classification. The HCl digestion method was used
      to isolate the crypts. For scanning electron microscopy observations of the
      surface structure, specimens were mounted on brass stubs, coated with gold, and
      then observed. RESULTS: In isolated crypts with bifurcation extending to the
      middle or all the way to the lesion surface, the crypt orifice was round with a
      type IIIS pit pattern. In those with bifurcations extending up to the upper
      portion, the crypt orifice was oval with a type IIIS pit pattern. Some crypts
      were almost completely separated into two. The orifice diameter of a
      nonbifurcated crypt was 95.1 +/- 28.1 microm, whereas the diameters of crypts
      with bifurcations extending to the middle or the upper part were 114.7 +/- 40.8
      and 208.1 +/- 71.4 microm, respectively. Thus, the orifice diameter of a crypt
      with the bifurcation reaching the upper part was about twice that of orifices of
      nonbifurcated crypts or those with bifurcations extending to the middle.
      CONCLUSIONS: Our results indicate that colorectal neoplasms with depressions may
      enlarge by a process of crypt bifurcation in which a single crypt divides into
      two crypts.

PMID- 18709480
TI  - Endoscopic characterization of the small bowel in patients with portal
      hypertension evaluated by double balloon endoscopy.
AB  - BACKGROUND: The endoscopic abnormalities present in the small bowel (SB) of
      patients with portal hypertension (PH) are not well understood. This study sought
      to evaluate endoscopic findings of the SB in patients with PH by double balloon
      endoscopy (DBE). METHODS: We evaluated the endoscopic findings of SB in 15
      patients with PH and 49 controls without liver disease or PH. A total of 24 and
      90 procedures were performed for PH patients and control patients, respectively,
      through oral and/or anal approaches. RESULTS: Fourteen of the 15 patients
      exhibited villous abnormalities, including edema (73%), atrophy (40%), and
      reddening (47%) of villi. Vascular lesions, such as angiodysplasia-like
      abnormalities (67%), dilated/proliferated vessels (93%), and varices (7%), were
      observed in all patients with PH. Although they were associated with ascites,
      these abnormalities did not correlate with any laboratory findings. None of these
      abnormalities was observed in controls. Definitive or suspected bleeding sources
      were identified in 9 of 13 patients with both PH and obscure gastrointestinal
      bleeding (OGIB), which was similar to the incidence in controls with OGIB.
      Although the frequency of postprocedure fever (>37.5 degrees C) was higher in
      patients with PH in comparison to controls (29% vs. 2%, P < 0.01), endoscopic
      treatment under DBE was performed on 3 PH patients without serious complications.
      CONCLUSIONS: Endoscopic abnormalities of the SB may be prevalent in patients with
      PH. Although postprocedure fever of DBE may occur more commonly in patients with
      PH, DBE is useful as both a diagnostic and therapeutic tool to evaluate the SB.

PMID- 18709482
TI  - Impaired autonomic function in type 2 diabetic patients during upper
      gastrointestinal endoscopy.
AB  - BACKGROUND: Cardiac autonomic neuropathy, representing decreased parasympathetic
      nerve activity and predominance of sympathetic tone, is often encountered in
      diabetic patients, and leads to an increased risk of cardiovascular events
      including arrhythmia. To evaluate the potential cardiovascular risk of diabetics
      in performing esophagogastroduodenoscopy (EGD), we compared the autonomic
      function and cardiovascular parameters during EGD between diabetic and
      nondiabetic patients. METHODS: The autonomic nervous responses in 86 consecutive
      outpatients (42 type 2 diabetics and 44 nondiabetics) were determined by power
      spectral analysis (PSA) of heart-rate variations on an electrocardiogram. PSA
      data were based on two peaks in the low-frequency (LF) and high-frequency (HF)
      ranges. HF power and the ratio of LF power/HF power represented parasympathetic
      and sympathetic nerve activities, respectively. RESULTS: Diabetic patients showed
      significantly lower DeltaHF power and significantly higher DeltaLF power/HF power
      than nondiabetics, suggesting enhanced predominance of sympathetic activity and
      marked suppression of parasympathetic function. Significant correlations were
      found between these autonomic parameters and the diabetic duration. A slightly
      higher incidence of ventricular premature contractures was observed in diabetics
      during EGD. However, no significant difference was found in pulse or blood
      pressure increments during EGD between the two groups. CONCLUSIONS: This is the
      first study demonstrating an imbalance of autonomic function in diabetics during
      EGD, which may be linked to a slightly higher risk of arrhythmia.

PMID- 18709484
TI  - Prohibitin: a potential biomarker for tissue-based detection of gastric cancer.
AB  - BACKGROUND: Prohibitin (PHB) was found to be overexpressed in breast cancer and
      thus is suggested as a biomarker in that disease. A few studies have investigated
      the PHB expression pattern in gastric cancer by two-dimensional gel
      electrophoresis. Uncertainties still existed on whether PHB expression could
      indicate the differentiation and apoptosis degree of gastric cancer and whether
      PHB protein as well as anti-PHB antibody could be a biomarker in the serum of the
      gastric cancer patient. In this study, the expression levels of PHB protein and
      mRNA of the tissues as well as PHB antigen and anti-PHB antibody in serum of
      patients with gastric cancer were systemically examined. METHODS:
      Immunohistochemistry and real-time PCR were used to detect expression levels of
      PHB protein and mRNA in gastric cancer tissues. Recombinant PHB antigen was
      identified by Western blotting. The expression of PHB antigen and anti-PHB
      antibody was investigated by ELISA and TRFIA. Bcl-2 expression was examined by
      immunohistochemistry. RESULTS: By immunohistochemistry and real-time PCR
      analyses, PHB protein and mRNA were both overexpressed in gastric cancer tissues
      compared to adjacent normal gastric tissues (P < 0.01). Moreover, an elevated PHB
      expression pattern paralleled the differentiation degree and Bcl-2 protein
      expression in gastric cancer. However, no significant differences of PHB protein
      and anti-PHB antibody expression were detected in serum of gastric cancer
      patients and that of healthy volunteers. CONCLUSIONS: These results indicated
      that PHB could be a potential diagnostic and differentiation biomarker of gastric
      cancer for tissue-based detection by immunohistochemistry and real-time PCR, but
      not for serum-based detection.

PMID- 18709483
TI  - Long-term effects of lipase inhibition by orlistat on gastric emptying and
      orocecal transit time of a solid meal.
AB  - BACKGROUND: We assessed the impact of a prolonged lipase inhibition upon gastric
      emptying (GE) and orocecal transit time (OCTT) of a 355-kcal low-fat solid meal.
      METHODS: In double-blind manner, 40 obese women BMI > 30 kg/m2, randomly
      allocated into two equal groups, took orally t.i.d. 120 mg orlistat or placebo
      during 8 weeks of a weight-reducing management. At randomization and after 2
      months, GE was measured simultaneously with OCTT by means of a 13C-octanoic acid
      and a hydrogen breath test, respectively. Lipolytic activity was evaluated with a
      13C-mixed triglyceride breath test (13C-MTGBT). RESULTS: A profound lipase
      inhibition by orlistat was confirmed by a 79.5% +/- 16.9% reduction of the
      cumulative 6-h 13C recovery with 13CMTGBT. GE remained unchanged either in the
      orlistat (T1/2, 188 +/- 35 min start versus 198 +/- 36 min end) or the placebo
      (T1/2, 191 +/- 35 min start versus 180 +/- 39 min end) group. OCTT increased from
      208 +/- 54 min to 271 +/- 64 min (P < 0.01) after orlistat treatment and did not
      change significantly (216 +/- 76 vs. 234 +/- 72 min) in the placebo group.
      CONCLUSIONS: No adverse effect on the GE and a moderate prolongation of the OCTT
      of a low-fat solid meal is to be expected under a prolonged treatment with
      orlistat at a typical dosage regimen.

PMID- 18709486
TI  - Liver/spleen volume ratio as a predictor of prognosis in primary biliary
      cirrhosis.
AB  - BACKGROUND: The course of primary biliary cirrhosis (PBC) is determined by
      clinical symptoms and histological findings. The present study examined the
      prognostic importance of imaging parameters in PBC. METHODS: The volumes of the
      liver and spleen of patients with PBC were assessed by computed tomography (CT).
      The volume ratio of liver to spleen (LV/SV ratio) was evaluated and used for
      further analyses. RESULTS: The prognosis was significantly poorer in PBC patients
      with a low, rather than high, LV/SV ratio. The Cox proportional hazard regression
      model showed that the serum bilirubin level and the LV/SV ratio could predict the
      prognosis of PBC patients. In addition, the LV/SV ratio was significantly lower
      in patients who developed symptoms (s-PBC) than in those who remained
      asymptomatic (a-PBC) during the observation period. CONCLUSIONS: The LV/SV ratio
      is of prognostic importance in patients with PBC.

PMID- 18709485
TI  - Phenotypic alteration of interstitial cells of Cajal in idiopathic sigmoid
      megacolon.
AB  - BACKGROUND: Interstitial cells of Cajal (ICCs) are detected as a pacemaker of
      gastrointestinal movement and express c-kit and CD34. Recently, ICCs have
      implicated pathogenesis in several human diseases presenting gastrointestinal
      motor dysfunction. This study was performed to clarify the role of ICCs in
      idiopathic sigmoid megacolon using histological and immunohistochemical
      examinations. METHODS: Four adult patients with idiopathic sigmoid megacolon and
      11 controls were studied. Histology and immunocytochemistry using NSE, S100, c
      kit, and CD34 were performed in conjunction with quantitative analysis using the
      public domain NIH image program. RESULTS: Little histological change in
      neuromuscular structures in megacolon was observed. Immunohistochemistry
      demonstrated remarkable decrease of c-kit expressing ICCs without reduction of
      CD34 expression in the similar interstitial cell population. This observation was
      further supported by quantitative assessment using public domain NIH image
      program. CONCLUSIONS: A specific downregulation of c-kit in ICCs may be a cause
      of idiopathic sigmoid megacolon in adults.

PMID- 18709487
TI  - Temporary endosonography-guided biliary drainage for transgastrointestinal
      deployment of a self-expandable metallic stent.
AB  - Endosonography-guided biliary drainage (ESBD) is now gaining acceptance as a
      useful alternative for the management of obstructive jaundice.(1) At present,
      ESBD is used mainly to establish an anastomosis between the biliary tree and the
      duodenum, stomach, jejunum, or esophagus by placing a stent so as to bridge the
      bile duct and alimentary tract. We herein report a new application of ESBD, that
      is, its temporary use for gaining access to the bile duct in order to deploy a
      self-expandable metallic stent (SEMS) via the transhepatic route. In a patient
      with pylorus stenosis due to advanced gastric cancer with extrahepatic bile duct
      obstruction caused by nodal metastasis, a plastic stent was placed temporarily by
      ESBD to bridge the esophagus and the left hepatic duct. Ten days later, the stent
      was retrieved, leaving a guidewire in the bile duct, and a delivery unit of a
      SEMS was introduced into the bile duct over the guidewire via the sinus tract.
      The SEMS was then successfully deployed through the stenosis. No stent was left
      in the sinus tract. This procedure yields a mature fistula through which a
      delivery unit can be safely introduced into the bile duct followed by uneventful
      deployment of a SEMS.

PMID- 18709488
TI  - Screening of Taxol-producing fungi based on PCR amplification from Taxus.
AB  - Genes coding for 10-deacetylbaccatin III-10-O-acetyl transferase and C-13
      phenylpropanoid side chain-CoA acyltransferase were used as molecular markers for
      screening of Taxol-producing endophytic fungi. Using PCR, three out of 90
      endophytic fungi, isolated from Taxus x media and Taxus yunnanensis, gave
      positive results. These 3 strains, when grown in 300 ml potato/dextrose liquid
      medium at 25 degrees C for 10 days, contained 100-160 microg Taxol/g dry wt of
      mycelium.

PMID- 18709490
TI  - Effects of nano-anatase on ribulose-1, 5-bisphosphate carboxylase/oxygenase mRNA
      expression in spinach.
AB  - Being a proven photocatalyst, nano-anatase is capable of undergoing electron
      transfer reactions under light. In previous studies, we had proven that nano
      anatase improved photosynthesis and greatly promoted spinach growth. However, the
      molecular mechanisms of carbon reaction promoted by nano-anatase are still not
      clearly understood. In the present paper, reverse transcription polymerase chain
      reaction and Northern blotting were carried out, and the results showed that the
      expression of ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) small
      subunit (rbcS) and Rubisco large subunit (rbcL) messenger RNA (mRNA) in the nano
      anatase-treated spinach were obviously promoted, respectively, while the effects
      of bulk TiO2 were not so significant. Accordingly, the protein expression of
      Rubisco from the nano-anatase-treated spinach was increased by 40% compared with
      control. Further analysis indicated that the activity of Rubisco in the nano
      anatase-treated spinach was significantly higher than the control, by up to 2.33
      times, and bulk TiO2 treatment had no such significant effects. Together, one of
      the molecular mechanisms of carbon reaction promoted by nano-anatase is that the
      nano-anatase treatment results in the enhancement of Rubisco mRNA amounts, the
      protein levels, and activity of Rubisco, thereby leading to the improvement of
      Rubisco carboxylation and the high rate of photosynthetic carbon reaction.

PMID- 18709489
TI  - Systemic delivery of DNA or siRNA mediated by linear polyethylenimine (L-PEI)
      does not induce an inflammatory response.
AB  - PURPOSE: The success of nucleic acid therapies depends upon delivery vehicle's
      ability to selectively and efficiently deliver therapeutic nucleic acids to
      target organ with minimal toxicity. The cationic polymer polyethylenimine (PEI)
      has been widely used for nucleic acid delivery due to its versatility and
      efficiency. In particular, the last generation of linear PEI (L-PEI) is being
      more efficient in vivo than the first generation of branched PEI. This led to
      several clinical trials including phase II bladder cancer therapy and human
      immunodeficiency virus immunotherapy. When moving towards to the clinic, it is
      crucial to identify potential side-effects induced by the delivery vehicle.
      MATERIALS AND METHODS: For this purpose we have analyzed the production of pro
      inflammatory cytokines [tumor necrosis factor-alpha, interferon (IFN)-gamma,
      interleukin (IL)-6, IL-12/IL-23, IFN-beta and IL-1beta] and hepatic enzyme levels
      (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and
      alkaline phosphatase) in the blood serum of mice after systemic injection of DNA
      or siRNAs delivered with L-PEI. RESULTS: Our data show no major production of pro
      inflammatory cytokines or hepatic enzymes after injection of DNA or
      oligonucleotides active for RNA interference (siRNAs or sticky siRNAs) complexed
      with L-PEI. Only a slight induction of IFN-gamma was measured after DNA delivery,
      which is probably induced by the CpG mediated response. CONCLUSION: Taken
      together our data highlight that linear polyethylenimine is a delivery reagent of
      choice for nucleic acid therapeutics.

PMID- 18709491
TI  - Effect of zinc and copper on the interaction of daunorubicin with cardiac myosin.
AB  - Daunorubicin (DNR) is an anthracyline antibiotic which induces a well-described
      but incompletely understood cardiac toxicity. In this study, a direct action of
      DNR on the major contractile protein, cardiac myosin (CM), was described
      utilizing the fluorescence spectroscopy. The quenching mechanism was suggested to
      be static quenching according to the fluorescence measurement. In particular, the
      effects of common ions on the binding constants of DNR with CM were also
      investigated under physiological conditions, and the quenching constant K(SV) and
      binding constant K(LB) were obtained at room temperature. These data proved that
      Zn2+ and/or Cu2+ potentiated quenching fluorescence intensity of DNR-CM complex.
      Moreover, the normal ratio of Zn2+ to Cu2+ was able to competitively inhibit the
      binding interaction of DNR with CM, which might contribute to exert the most
      significant cardioprotective effect and guarantee the contractile machinery of
      cardiac muscle.

PMID- 18709492
TI  - Gender differences in correlations between the content of elements in rain water
      and the frequency of hospitalization for arterial hypertension, chronic
      obstructive pulmonary disease, and psoriasis in Opole Voivodship, Poland, during
      2000-2002.
AB  - The aim of this work is to show and give a plausible explanation to gender
      dependent differences in correlations between the content of selected elements in
      rainwater and the frequency of hospitalization by reason of arterial
      hypertension, chronic obstructive pulmonary disease (COPD), and psoriasis in the
      area of Opolskie Voivodeship, Poland, during the period 2000-2002. The elements
      analyzed were sodium, potassium, calcium, magnesium, manganese, iron, total
      phosphorus, total nitrogen, ammonium nitrogen, zinc, copper, lead, cadmium,
      nickel, chromium, chloride, nitrate, and sulfate. Hospitalization due to arterial
      hypertension was more frequent in women, whereas those for COPD and psoriasis
      were more frequent in men. In the case of women hospitalized for arterial
      hypertension, the correlations were low, except for zinc (r = 0.47) and for
      cadmium (r = 0.43). In men hospitalized for COPD, all of the correlation
      coefficients were higher than 0.4, except for phosphorus. The coefficients for
      nickel, ammonia nitrogen, and total nitrogen ranged from 0.5 to 0.6 and the
      remaining elements from 0.6 to 0.7. In women, the correlation was limited to five
      elements where the coefficient was r > 0.4 for chloride, calcium, nitrate,
      phosphorus, and chromium. In cases of hospitalization for psoriasis, the
      correlation in men was between 0.4 and 0.5 for chloride, phosphorus, copper,
      lead, and total nitrogen and greater than 5 for sulfate, potassium, calcium,
      iron, manganese, nitrate, and ammonium nitrogen. The correlation in women was
      between 0.48 and 0.5 for ammonium nitrogen and phosphorus.

PMID- 18709493
TI  - Effects of lead on hepatic antioxidant status and transcription of superoxide
      dismutase gene in pigs.
AB  - Ninety-six castrated boars (Duroc x Landrace x Yorkshire) were randomly divided
      into four groups, each of which was replicated three times with eight pigs. The
      groups received the same basal diet supplemented with 0, 5, 10, and 20 mg/kg
      lead, respectively. The malondialdehyde and glutathione levels, antioxidant
      enzymes activities, and zinc/copper superoxide dismutase (Zn/Cu SOD) mRNA content
      in the liver were determined to evaluate the lead hepatic intoxication caused by
      the lead. Results showed the increased lipid peroxides level and the reduced
      glutathione content, along with a concomitant decrease in the activities of
      superoxide dismutase, catalase, and glutathione peroxidase. Moreover, the level
      of hepatic Zn/Cu SOD mRNA was also significantly reduced. We suggest potential
      mechanism for lead intoxication in liver as follows: lead causes parallel
      decrease in Zn/Cu SOD mRNA and activities of antioxidant enzymes, leading to the
      declined ability of scavenging free radicals with excessive production of lipid
      peroxides, which seriously damages the hepatic structure and function.

PMID- 18709494
TI  - Foot-shock stress-induced regional iron accumulation and altered iron homeostatic
      mechanisms in rat brain.
AB  - Like in other organs, iron in the brain plays an important role in various
      biological processes. Previous studies have shown that systemic iron homeostasis
      in mammalians was changed under specific stress conditions. The present study
      aimed to investigate effects of stress on brain iron homeostasis in rats using a
      foot-shock stress model. Young adult male Sprague-Dawley rats were randomly
      assigned to foot-shock stress group subjected to 30 min of cutaneous foot-shock
      (0.80 mA, 1 pulse/s, 300 ms duration) daily for 1 week or control group left
      undisturbed. Then, the rats were sacrificed and iron concentration in serum,
      liver, and some brain regions were measured using atomic absorption
      spectrophotometry. Expression of ferritin, Transferrin receptor (TfR), divalent
      metal transporter 1 (DMT1, with or without iron-responsive element), lactoferrin
      (Lf), and iron regulatory protein 1 (IRP1) in rat hippocampus were determined
      using western blot analysis. The results showed that stress induced decreased
      serum iron concentration, increased liver iron content, and elevated iron
      contents in specific brain regions including hippocampus, striatum, and frontal
      cortex. In the hippocampus, stress caused decreased expression of ferritin,
      increased expression of TfR and IRP1, and no change in expression of DMT1 or Lf.
      Results of this study demonstrated that foot-shock stress induced region specific
      iron accumulation and altered iron homeostatic mechanisms in the brain in
      addition to a changed systemic iron homeostasis characterized by decreased serum
      iron concentration and increased liver iron content. And, elevated IRP1
      expression might be associated with the increased TfR and decreased ferritin
      expression, leading to subsequent iron accumulation and possible increased
      vulnerability to oxidative damage in hippocampus.

PMID- 18709495
TI  - Evidence-Based Knowledge Management: an approach to effectively promote good
      health-care decision-making in the Information Era.
AB  - The sharing of information and the growth of knowledge together represent a
      foundation for the promotion of quality improvement of health care systems. This
      paper concerns knowledge, not only from an epistemological point of view, but
      also from a pragmatic one. In our paper, knowledge is discussed as the hub to
      promote better decision making and continuous professional development. Effective
      thinking is particularly needed. The critical point is to think about how health
      care systems can develop both an effective knowledge management network and how
      health-care organizations can actually be based on it. In this way, knowledge and
      knowledge hierarchy are defined according to Russel Achkoff's vision. Generally,
      knowledge is crucial in decision-making, and Evidence-Based Medicine has its
      roots in knowledge. In particular, information management is the basis for a
      significant production of knowledge to promote good health-care decision-making.
      Thus, relationships between knowledge management and Evidence-Based Medicine are
      discussed, and a new paradigm is proposed: the Evidence-Based Knowledge
      Management. Finally, the role of Evidence-Based Knowledge Management within
      Clinical Governance is discussed together with some considerations about clinical
      governance implementation problems in Italy.

PMID- 18709496
TI  - Food allergy and food intolerance: diagnosis and treatment.
AB  - Food allergy is a matter of concern because it affects about 0.5-3.8% of the
      paediatric population and 0.1-1% of adults, and as well may cause life
      threatening reactions. Skin prick testing with food extracts and with fresh
      foods, the measurement of food-specific IgE, elimination diets and a double
      blind, placebo-controlled food challenge are the main diagnostic procedures; many
      non-validated procedures are available, creating confusion among patients and
      physicians. The treatment of food allergy is still a matter of debate.
      Antihistamines, corticosteroids and, if necessary (in case of anaphylaxis),
      epinephrine, are the drugs of choice for the treatment of symptoms of food
      allergy. Sodium cromolyn may be used prophylactically even though there are no
      controlled studies certifying its efficacy. The only etiologic treatment of food
      allergy is specific desensitization. Sublingual-oral-specific desensitization has
      been used by our group for the treatment of food-allergic patients with a high
      percentage of success.

PMID- 18709498
TI  - Fluoride occurrence and assessment of exposure dose of fluoride in shallow
      aquifers of Makur, Unnao district Uttar Pradesh, India.
AB  - The water samples from the shallow aquifers of Makur, Unnao district, Uttar
      Pradesh, was analyzed for fluoride content (F( - )) and other water quality
      parameters such as pH, EC, CO(3) (2-), HCO(3) (-), Cl( - ), Na( + ), Ca(2 + ),
      Mg(2 + ) and RSC. It was found that the F( - ) concentration of water varied
      between 1.05 to 13.9 mgl( - 1) which exceeded the maximum desirable limits of 1.0
      mgl( - 1) of F( - ) as laid down by BIS and 68% of water exceeded maximum
      permissible limits of 1.5 mgl( - 1) as prescribed by WHO. The correlation study
      of fluoride indicated that F( - ) has a significant (p < 0.05) positive
      relationship with pH (r = +0.59) and RSC (r = 0.54), while a significant negative
      correlation with Ca+Mg (r = -0.53) and Mg (r = -0.49). The exposure doses of
      fluoride in infants was found between 0.35 to 3.26 mg kg( - 1)day( - 1) (if dug
      well water was used) whereas 0.36 to 4.63 mg kg( - 1)day( - 1) (when shallow hand
      pumps) The exposure doses of water in case of children (20 kg body weight) varied
      between 0.157 to 1.47 mg kg( - 1)day( - 1) (for dugwell) and 0.162 to 2.08 mg kg(
      - 1)day( - 1) (for shallow hand pumps) whereas in case of adults (70 kg body
      weight), it varied between 0.09 to 0.839 mg kg( - 1)day( - 1) (for dugwell) and
      0.092 to 1.19 mg kg( - 1)day( - 1) (shallow hand pumps) which is quite high
      against the standard value of 0.05 mg/kg/day which is the minimum risk level
      (MRL) calculated by the Agency for Toxic Substances and Disease Registry (ATSDR).
      The maximum exposure dose to fluoride for adults in the study area found to be
      23.8 times higher than the ATSDR's MRL.

PMID- 18709499
TI  - Physiological-biochemical properties of blue mussel Mytilus edulis adaptation to
      oil contamination.
AB  - Bivalves have a known ability to accumulate different contaminants from ambient
      water and can therefore serve as bioindicators. The paper analyses certain
      biochemical and physiological parameters of blue mussels in response to varying
      oil product concentrations. The heart rate (HR) of blue mussels from the
      sublittoral zone exposed to different levels of oil products was investigated in
      a long-term experiment using non-invasive monitoring. A sharp rise in HR was
      observed at oil concentrations of 8.0 and 38.0 mg/l. A decreasing in mussel HR
      under the effect of lower concentrations (0.4 and 1.9 mg/l) was significant on
      the fourth day. Strong fluctuations of the cardiac activity were noted under all
      concentrations. After 6 days of oil treatment, tissues of the mussels were
      sampled to determine the total lipid composition. Low concentrations of oil
      products produced no reliable changes in the lipid composition whereas high
      concentrations induced significant changes in the ratio of lipid components
      (cholesterol and phospholipids).

PMID- 18709500
TI  - Response requirements modulate tactile spatial congruency effects.
AB  - Several recent studies have provided support for the view that tactile
      stimuli/events are remapped into an abstract spatial frame of reference beyond
      the initial somatotopic representation present in the primary somatosensory
      cortex. Here, we demonstrate for the first time that the extent to which this
      remapping of tactile stimuli takes place is dependent upon the particular demands
      imposed by the task that participants have to perform. Participants in the
      present study responded to either the elevation (up vs. down) or to the
      anatomical location (finger vs. thumb) of vibrotactile targets presented to one
      hand, while trying to ignore distractors presented simultaneously to the other
      hand. The magnitude and direction of the target-distractor congruency effect was
      measured as participants adopted one of two different postures with each hand
      (palm-up or palm-down). When the participants used footpedal responses (toe vs.
      heel; Experiment 1), congruency effects were determined by the relative elevation
      of the stimuli in external coordinates (same vs. different elevation), regardless
      of whether the relevant response feature was defined externally or anatomically.
      Even when participants responded verbally (Experiment 2), the influence of the
      relative elevation of the stimuli in external space, albeit attenuated, was still
      observed. However, when the task involved responding with the stimulated finger
      (four-alternative forced choice; Experiment 3), congruency effects were virtually
      eliminated. These findings support the view that tactile events can be remapped
      according to an abstract frame of reference resulting from multisensory
      integration, but that the frame of reference that is used while performing a
      particular task may depend to a large extent on the nature of the task demands.

PMID- 18709501
TI  - Splenic marginal zone B-cell lymphoma in a HIV-positive patient: a case report.

PMID- 18709502
TI  - Sequential continuous infusion of fludarabine and cytarabine associated with
      liposomal daunorubicin (DaunoXome) (FLAD) in primary refractory or relapsed adult
      acute myeloid leukemia patients.
AB  - A large proportion of adult patients with acute myeloid leukemia (AML) relapse
      after treatment, and some of them are resistant to primary induction
      chemotherapy. Sixty-one patients from seven hematological centers with poor-risk
      AML, primary refractory (n = 16), or relapsed (n = 45) were treated with a
      salvage regimen, including fludarabine (2 days) and cytarabine (3 days) in a
      sequential continuous infusion, associated with liposomal daunorubicin (3 days)
      (FLAD). Complete response rate was 44% and 56% for refractory and relapsed
      patients, respectively, with an overall response rate of 52% (32 of 61). Twenty
      two patients (36%) were resistant to the salvage therapy. Seven patients (12%)
      died early during chemotherapy, four of them because of sepsis. Nineteen patients
      in complete remission (CR) underwent a stem-cell transplant (SCT) procedure: five
      autologous, nine from a HL-A identical sibling, and five from HL-A matched
      unrelated donors. Post-treatment aplasia and mucositis were major toxicities.
      Twenty patients (62.5%) relapsed after this treatment in a median of 7.3 months;
      ten patients relapsed after a SCT procedure. Nine patients are alive and disease
      free; three of them were rescued after a further cytotoxic treatment. The FLAD
      regimen proved to be an effective and well-tolerated treatment, with acceptable
      toxicity in this group of high-risk patients. A better response rate was obtained
      in the subgroup of relapsed patients, compared to patients treated for refractory
      disease. More then half (five of nine) of long-surviving patients are those who
      were submitted to a transplant procedure; thus, the main indication for FLAD
      seems to be to try to induce a rapid CR with minimum toxicity in order to perform
      a transplant as soon as possible.

PMID- 18709503
TI  - Leptomeninges as the first and only dissemination site of colorectal cancer.

PMID- 18709504
TI  - Somatic mosaicism for a PDHA1 mutation in a female with pyruvate dehydrogenase
      deficiency.
AB  - Somatic mosaicism for a mutation in the X-linked PDHA1 gene was found in a girl
      who presented with manifestations of pyruvate dehydrogenase deficiency. Mutation
      in the PDHA1 gene was suggested by a mosaic pattern of E1alpha subunit
      immunostaining; however, initial screening of cDNA and the exons and intron-exon
      boundaries yielded only normal sequence, apart from a heterozygous 4 bp insertion
      in intron 10. This was considered to be a polymorphism as it is also present in
      her unaffected mother who has normal enzyme activity and uniform E1alpha
      immunostaining in fibroblasts. Detailed genetic analysis, which included
      isolation of cloned fibroblasts expressing the mutant X chromosome, resulted in
      the identification of a base substitution in the acceptor splice site of intron 9
      which leads to activation of a cryptic upstream splice site. The proportion of
      cells expressing the mutation was then determined by direct analysis of the X
      inactivation pattern. Genetic diagnosis in this unique case of PDHA1 somatic
      mosaicism was complicated by the absence of an abnormal transcript in primary
      fibroblasts, the presence of three different alleles and an X-inactivation
      pattern favouring expression of the normal, paternal, X chromosome. Although the
      mutation was only present in a proportion of cells, and only expressed in a
      subset of these due to random X-inactivation, the resulting enzyme defect was
      sufficient to be clinically apparent.

PMID- 18709505
TI  - Postoperative fever and survival in patients after open resection for colorectal
      cancer: a long-term follow-up study of 2,311 prospectively enrolled patients.
AB  - PURPOSE: Two reports on the impact of postoperative fever on survival after
      surgery in patients with colorectal cancer yielded contradictory results. Our
      study examined possible associations between postoperative fever and long-term
      survival of patients who underwent resection of colorectal cancer. METHODS: We
      investigated 2,311 consecutive patients who underwent elective open colorectal
      resection for primary colorectal cancer at a single institution between 1995 and
      1998. The primary end points were cancer-specific and overall survival. Multiple
      covariate impact of risk factors on survival rates was assessed by Cox regression
      analysis. RESULTS: A total of 252 patients (12.2 percent) developed postoperative
      fever. The most important independent risk factor for postoperative fever was
      postoperative morbidity (odds ratio, 4.9; 95 percent confidence interval, 3.7
      6.6) followed by blood transfusion (1.7; 1.2-2.2), Stage IV disease (1.6; 1.1
      2.2), male gender (1.4; 1.0-1.9), and rectal cancer (1.4; 1.0-1.8). Cox
      regression modeling indicated that stage, histology, tumor location, and blood
      transfusion were statistically significant covariate predictors for cancer
      specific survival. Postoperative fever was not independently associated with
      cancer-specific or overall survival. CONCLUSIONS: This study did not support the
      hypothesis that postoperative fever is an independent prognostic factor after
      colorectal resection for primary colorectal cancer.

PMID- 18709506
TI  - Plant-herbivore-carnivore interactions in cotton, Gossypium hirsutum: linking
      belowground and aboveground.
AB  - Most studies on plant-herbivore interactions focus on either root or shoot
      herbivory in isolation, but above- and belowground herbivores may interact on a
      shared host plant. Cotton (Gossypium spp.) produces gossypol and a variety of
      other gossypol-like terpenoids that exhibit toxicity to a wide range of
      herbivores and pathogens. Cotton plants also can emit herbivore-induced volatile
      compounds at the site of damage and systemically on all tissues above the site of
      damage. As these volatile compounds attract natural enemy species of the
      herbivore, they are thought to represent an indirect plant defense. Our study
      quantified gossypol and gossypol-like compounds in cotton plants with foliage
      feeding (Heliocoverpa zea), root feeding (Meloidogyne incognita), or their
      combination. Cotton plants with these treatments were studied also with respect
      to induced local and systemic volatile production and the attraction of the
      parasitic wasp Microplitis croceipes to those plants. We also evaluated whether
      foliage or root feeding affected foliar nitrogen levels in cotton. After 48 hr of
      leaf feeding and 5 wk of root feeding, local and systemic induction of volatiles
      (known to attract parasitoids such as M. croceipes) occurred with herbivore
      damage to leaves, and it increased in levels when root herbivory was added.
      Nevertheless, M. croceipes were equally attracted to plants with both leaf and
      root damage and leaf damage only. In contrast to previous studies in cotton,
      production of gossypol and gossypol-like compounds was not induced in leaf and
      root tissue following foliage or root herbivory, or their combination. We
      conclude that root feeding by M. incognita has little influence on direct and
      indirect defenses of Gossypium hirsutum against insect herbivory.

PMID- 18709507
TI  - Hydrocarbon signals explain the pattern of worker and egg policing in the ant
      Aphaenogaster cockerelli.
AB  - In ant societies, worker reproduction is regulated through policing behaviors,
      such as physical aggression or egg eating. The information used by policing
      individuals is thought to be in blends of hydrocarbons present on the cuticle and
      the surface of eggs. These fertility signals have been studied in numerous
      genera. However, signaling patterns that emerge across distinct subfamilies of
      ants have yet to be explained. We investigated policing behavior and the chemical
      signaling upon which policing behaviors are informed in the ant Aphaenogaster
      cockerelli. We found that worker-produced eggs are not policed, and we showed
      that there is a lack of chemical signaling for effective egg policing to occur in
      this species. Furthermore, we identified the available signals that demarcate
      workers to be policed physically. We showed that in A. cockerelli, a species with
      derived social organization, workers produce fertility signals identical to the
      queen. This queen-like signaling may be due to workers maintaining a high level
      of ovarian activity, linked to trophic egg production, in the presence of the
      queen.

PMID- 18709508
TI  - Blood flow and glucose metabolism in stage IV breast cancer: heterogeneity of
      response during chemotherapy.
AB  - OBJECTIVE: The purpose of the study was to compare early changes in blood flow
      (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of
      patients treated with chemotherapy. METHODS: Eleven women with stage IV cancer
      and lesions in breast, lymph nodes, liver, and bone were scanned before treatment
      and after the first course of chemotherapy. BF, distribution volume of water
      (Vd), MRglu/BF ratio, MRglu and its corresponding rate constants K1 and k3 were
      compared per tumor lesion before and during therapy. RESULTS: At baseline, mean
      BF and MRglu varied among different tumor lesions, but mean Vd was comparable in
      all lesions. After one course of chemotherapy, mean MRglu decreased in all
      lesions. Mean BF decreased in breast and node lesions and increased in bone
      lesions. Vd decreased in breast and nodes, but did not change in bone lesions.
      The MRglu/BF ratio decreased in breast and bone lesions and increased in node
      lesions. In patients with multiple tumor lesions BF and MRglu response could be
      very heterogeneous, even within similar types of metastases. BF and MRglu
      increased in lesions of patients who experienced early disease progression or
      showed no response during clinical follow-up. CONCLUSION: BF and MRglu changes
      separately give unique information on different aspects of tumor response to
      chemotherapy. Changes in BF and MRglu parameters can be remarkably heterogeneous
      in patients with multiple lesions.

PMID- 18709509
TI  - Dual-time-point FDG-PET/CT for the detection of hepatic metastases.
AB  - PURPOSE: To prove the sensitivity of dual-time-point imaging with 18F
      flourodeoxyglucose-positron emission tomography (18F-FDG-PET) of the liver to
      evaluate possible changes in the tumor-to-background ratio considering an
      improved detection rate of liver lesions. PROCEDURES: Image acquisition for the
      first whole-body scan started at a mean time point of 69 min (55-110 min). The
      mean time interval between the injection of 18F-FDG and the second delayed scan
      was 100 min (85-166 min). RESULTS: Of 90 proven liver metastases in 34 patients,
      the first scan detected 53 (59%) liver lesions correctly, whereas in the second,
      delayed scan 81 (90%) lesions were diagnosed correctly (p<0.001). The mean
      Standardized uptake values in the first and second delayed scan were 6.59 g/ml
      versus 8.09 g/ml, respectively (p<0.001). Tumor-to-background ratio of the first
      and second delayed scan were 2.0 and 2.7, respectively (p=0.04). CONCLUSIONS:
      Dual-time-point-imaging of the liver showed a significant increase of tumor-to
      background ratio and hypermetabolic lesion diameter. Although, 30% of all
      verified liver lesions could only be detected in the second delayed scan 10% of
      all malignant liver lesions were missed with FDG-PET.

PMID- 18709510
TI  - The prognostic superiority of log odds of positive lymph nodes in stage III colon
      cancer.
AB  - BACKGROUND: Literature showed that lymph node ratio (LNR) and total number of
      lymph nodes (TNODS) are independent prognostic factors in node-positive colon
      cancer. Our study assesses the prognostic superiority of the log odds of positive
      lymph nodes (LODDS) in the same patient population. MATERIAL AND METHODS: A total
      of 24,477 stage III colon cancer cases from the SEER registry were reviewed.
      Patients were categorized based on LNR into LNR1 to LNR4, according to cutoff
      points 0.07, 0.25, and 0.50, and based on LODDS into LODDS1 to LODDS5, according
      to cutoff points -2.2, -1.1, 0, and 1.1. The relative risk (RR), and 95%
      confidence interval (CI) were evaluated using the method of Kaplan-Meier and Cox
      model. RESULTS: Patients with LNR4 could be classified into LODDS4 (61.4%) and
      LODDS5 (38.4%). The survival in these two groups was significantly different (5
      year survival, 33.5% vs. 23.3%, p < 0.0001). Univariate analysis showed that the
      higher LNR (RR = 3.45, 95% CI = 3.26-3.66) or low TNODS (RR = 0.99, 95% CI =
      0.986-0.99) was significantly associated with poor survival. However, after
      adjusting for LODDS status, the association did not appear to be significant
      (LNR, RR = 0.90, 95% CI = 0.65-1.24, p = 0.52; TNODS, RR = 1.001, 95% CI = 0.997
      1.005, p = 0.54). CONCLUSION: Colon cancer patients with LNR4 disease represent a
      heterogeneous group. The previously reported prognostic association of TNODS and
      LNR and outcome of stage III disease were confounded by LODDS.

PMID- 18709511
TI  - Medical or surgical management of GERD patients with Barrett's esophagus: the
      LOTUS trial 3-year experience.
AB  - INTRODUCTION: The long-term management of gastroesophageal reflux in patients
      with Barrett's esophagus (BE) is not well supported by an evidence-based
      consensus. We compare treatment outcome in patients with and without BE submitted
      to standardized laparoscopic antireflux surgery (LARS) or esomeprazole treatment.
      METHODS: In the Long-Term Usage of Acid Suppression Versus Antireflux Surgery
      trial (a European multicenter randomized study), LARS was compared with dose
      adjusted esomeprazole (20-40 mg daily). Operative difficulty, complications,
      symptom outcomes [Gastrointestinal Symptom Rating Scale (GSRS) and Quality of
      Life in Reflux and Dyspepsia (QOLRAD)], and treatment failure at 3 years and pH
      testing (after 6 months) are reported. RESULTS: Of 554 patients with
      gastroesophageal reflux disease, 60 had BE-28 randomized to esomeprazole and 32
      to LARS. Very few BE patients on either treatment strategy (four of 60)
      experienced treatment failure during the 3-year follow-up. Esophageal pH in BE
      patients was significantly better controlled after surgical treatment than after
      esomeprazole (p = 0.002), although mean GSRS and QOLRAD scores were similar for
      the two therapies at baseline and at 3 years. Although operative difficulty was
      slightly greater in patients with BE than those without, there was no difference
      in postoperative complications or level of symptomatic reflux control.
      CONCLUSION: In a well-controlled surgical environment, the success of LARS is
      similar in patients with or without BE and matches optimized medical therapy.

PMID- 18709512
TI  - Hepatic neuroendocrine metastases: chemo- or bland embolization?
AB  - INTRODUCTION: Aggressive management of hepatic neuroendocrine (NE) metastases
      improves symptoms and prolongs survival. Because of the rarity of these tumors,
      however, the best method for hepatic artery embolization has not been
      established. We hypothesized that in patients with hepatic NE metastases, hepatic
      artery chemoembolization (HACE) would result in better symptom improvement and
      survival compared to bland embolization (HAE). METHODS: Retrospective review
      identified all patients with NE hepatic metastases managed by HACE or HAE at
      three institutions from January 1996 through December 2007. RESULTS: We
      identified 100 patients managed by HACE (n = 49) or HAE (n = 51) that were
      similar with respect to age, gender, and primary tumor type. The percentage of
      patients experiencing morbidity, 30-day mortality, and symptom improvement were
      similar between the two groups (HACE vs. HAE: 2.4% vs. 6.6%; 0.8% vs. 1.8%; and
      88% vs. 83%, respectively.) No differences in the median overall survival were
      observed between HACE and HAE from the time of the first embolization procedure
      (25.5 vs. 25.7 months, p = 0.79). Multivariate analysis revealed that resection
      of the primary tumor predicted survival (73.8 vs. 19.4 months, p < 0.04).
      CONCLUSIONS: These data suggest that morbidity, mortality, symptom improvement,
      and overall survival are similar in patients with hepatic neuroendocrine
      metastases managed by chemo- or bland hepatic artery embolization.

PMID- 18709513
TI  - An FDA approved neurokinin-1 receptor antagonist is effective in reducing
      intraabdominal adhesions when administered intraperitoneally, but not orally.
AB  - INTRODUCTION: Postoperative adhesions pose a continued healthcare problem. We
      previously demonstrated that intraperitoneal (i.p.) administration of a
      neurokinin-1 receptor antagonist (NK-1RA) at surgery reduces intraabdominal
      adhesions in rats. The NK-1RA aprepitant (Emend, Merck) is clinically approved
      for preventing postoperative nausea and vomiting; however, its effects on
      adhesion formation are unknown. Thus, we determined the effects of i.p. and oral
      administration of aprepitant on adhesion formation in a rat model. METHODS:
      Adhesions were surgically induced in rats that were randomized to receive either
      one or five oral preoperative doses or a single intraoperative i.p. dose of
      aprepitant (50 mg/kg). Adhesions were scored at 7 days. In similar experiments
      using i.p. dosing, animals were sacrificed at 24 h and peritoneal fluid, and
      tissue were collected to assess fibrinolytic activity and tissue plasminogen
      activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) mRNA levels,
      respectively. RESULTS: I.p. aprepitant reduced adhesion formation by 33% (p <
      0.05) compared with controls while oral aprepitant had no effect. Compared to
      controls i.p. aprepitant reduced tPA activity by 55% (p < 0.05), increased PAI-1
      mRNA levels by 140% (p < 0.05), and had no affect on tPA mRNA levels. CONCLUSION:
      These data suggest that aprepitant maybe a useful pharmacologic agent for
      reducing adhesion formation clinically.

PMID- 18709514
TI  - Perioperative treatment with infliximab in patients with Crohn's disease and
      ulcerative colitis is not associated with an increased rate of postoperative
      complications.
AB  - PURPOSE: The impact of infliximab (IFX) on postoperative complications in
      surgical patients with Crohn's disease (CD) and ulcerative colitis (UC) is
      unclear. We examined a large patient cohort to clarify whether a relationship
      exists between IFX and postoperative complications. METHODS: A total of 413
      consecutive patients--188 (45.5%) with suspected CD, 156 (37.8%) with UC, and 69
      (16.7%) with indeterminate colitis--underwent abdominal surgery at the
      Massachusetts General Hospital between January 1993 and June 2007. One hundred
      one (24.5%) had received preoperative IFX < or = 12 weeks before surgery. These
      patients were compared to those who did not receive IFX with respect to
      demographics, comorbidities, presence of preoperative infections, steroid use,
      and nutritional status. We then compared the cumulative rate of complications for
      each group, which included deaths, anastomotic leak, infection, thrombotic
      complications, prolonged ileus/small bowel obstruction, cardiac, and hepatorenal
      complications. Potential risk factors for infectious complications including
      preexisting infection, pathological diagnosis, and steroid or IFX exposure were
      further evaluated using logistic regression analysis. RESULTS: Patients were
      similar with respect to gender (IFX = 40.6% men vs. non-IFX = 51.9%, p = 0.06),
      age (36.1 years vs. 37.8, p = 0.43), Charlson Comorbidity Index (5.3 vs. 5.7, p =
      0.25), concomitant steroids (75.3% vs. 76.9%, p = 0.79), preoperative albumin
      level (3.3 vs. 3.2, p = 0.36), and rate of emergent surgery (3.0% vs. 3.5%, p =
      1.00). IFX patients had higher rates of CD (56.4% vs. 41.9%, p = 0.02),
      concomitant azathioprine/6-mercaptopurine use (34.6% vs. 16.6%, p < 0.0001), and
      lower rates of intra-abdominal abscess (3.9% vs. 11%, p < 0.05). After surgery,
      the two groups had similar rates of death (2% vs. 0.3% p = 0.09), anastomotic
      leak (3.0% vs. 2.9%, p = 0.97), cumulative infections (5.97% vs. 10.1%, p = 1),
      thrombotic complications (3.6% vs. 3.0%, p = 0.06), prolonged ileus/small bowel
      obstructions (3.9 vs. 2.8, p = 0.59), cardiac complications (1% vs. 0.6%, p =
      0.42), and hepatic or renal complications (1.0 vs. 0.6% p = 0.72). A logistic
      regression model was then created to assess the impact of IFX, as well as other
      potential risk factors, on the rates of cumulative postoperative infections. We
      found that steroids (odds ratio [OR] = 1.2, p = 0.74), IFX (OR 2.5, p = 0.14),
      preoperative diagnosis of CD (OR = 0.7, p = 0.63) or UC (OR = 0.6, p = 0.48), and
      preoperative infection (OR = 1.2, p = 0.76) did not affect rates of clinically
      important postoperative infections. CONCLUSIONS: Preoperative IFX was not
      associated with an increased rate of cumulative postoperative complications.

PMID- 18709515
TI  - Totally transumbilical laparoscopic cholecystectomy.
AB  - A recently convened Consortium at the Cleveland Clinic agreed on the term Laparo
      Endoscopic Single-Site (LESS) surgery to describe minimally invasive techniques
      that use a single incision to accomplish laparoscopic procedures. These
      procedures are done by using either a single port through one fascial incision or
      multiple ports placed through separate fascial incisions. Because of cost
      containment issues and the lack of widespread availability of a single port, we
      currently use multiple reusable ports placed through three separate fascial
      incisions via a transumbilical incision. As opposed to standard laparoscopic
      cholecystectomy, a deflecting laparoscope and one articulating instrument are
      utilized to improve the safety and ease of this procedure. Presented in this
      video are the steps necessary to perform a LESS cholecystectomy via a
      transumbilical incision with commercially available instruments.

PMID- 18709516
TI  - Comparison of neutralizing antibody assays for receptor binding and enzyme
      activity of the enzyme replacement therapeutic Naglazyme (galsulfase).
AB  - Most patients receiving Naglazyme (galsulfase, rhASB) enzyme replacement therapy
      for mucopolysaccharidosis type VI develop an antibody response. To evaluate the
      impact of this response, two in vitro neutralizing antibody (NAb) assays were
      developed based on the two steps of the mechanism of action. Neutralization of
      enzyme activity was detected by inhibition of rhASB cleavage of a fluorogenic
      substrate. Neutralization of receptor binding was detected by decreased binding
      of labeled rhASB to immobilized soluble receptor. For the enzyme activity NAb
      assay, serum pretreatment was required to isolate antibodies from interfering
      phosphate ions, with sensitivity of < or =5 microg/mL. The receptor binding NAb
      assay used a five-fold dilution, with sensitivity of < or =40 microg/mL.
      Cutpoints for percent inhibition were based on 95% confidence intervals from
      naive sera. Clinical samples were similarly likely to be positive in both assays
      than positive for neutralization of only one step in the mechanism of action. The
      two NAb assays yielded complementary information about potential neutralization
      of rhASB. Relative estimated sensitivity between neutralization assays did not
      correlate with the number of positive clinical samples or patients. In vitro NAb
      assays based on a well-understood mechanism of action provide specific
      information about the NAb mechanism.

PMID- 18709518
TI  - Parathyroid hormone analogues in the therapy of osteoporosis.

PMID- 18709519
TI  - [Diagnosis and therapy of acute ureteral colic].
AB  - Acute ureteral colic presents with a complex of acute and characteristic flank
      pain that usually indicates the presence of a stone in the urinary tract.
      Diagnosis and management of renal colic have undergone considerable evolution and
      advancement in recent years. The application of noncontrast helical computed
      tomography (CT) in patients with suspected ureteral colic is one major advance in
      the primary diagnostic process. The superior sensitivity and specificity of
      helical CT allow ureterolithiasis to be diagnosed without the potential side
      effects of contrast media. Initial management is based on three key concepts: (A)
      rational and fast diagnostic process (B) effective pain control (C) and
      understanding of the impact of stone location and size on the natural course of
      the disease and definitive urologic management. These concepts are discussed in
      this review with reference to contemporary literature.

PMID- 18709520
TI  - Wellens' sign.

PMID- 18709521
TI  - Surgical revision of hemorrhage in 8388 patients after cold-steel
      adenotonsillectomies.
AB  - PURPOSE OF THE INVESTIGATION: Tonsillectomy and adenoidectomy are the most common
      surgical procedures in otorhinolaryngology. The most serious complication is
      postoperative hemorrhage, with a 2-4% risk of substantial bleeding. The aim of
      this study was to evaluate the incidence of and possible predictive factors for
      postoperative hemorrhage requiring surgical revision in patients undergoing cold
      dissection tonsillectomy/adenoidectomy. BASIC PROCEDURES: We performed a single
      institution retrospective study of 8388 patients who underwent tonsillectomy
      and/or adenoidectomy between 1994 and 2006. Tonsillectomy was performed using
      only cold-steel dissection with bipolar diathermy for hemostasis. MAIN FINDINGS:
      Hemorrhage occurred in 114 patients (1.78%) after tonsillectomy and in seven
      patients (0.35%) after adenoidectomy. After tonsillectomy 85.09% of the
      hemorrhages were secondary, occurring between the postoperative days 1 and 15,
      whereas in the adenoidectomy group 85.71% of the bleeding episodes were primary.
      Two patients (0.03%) required blood transfusions, none of the patients required
      an external carotid artery ligation, and there were no cases of death in our
      series. On the basis of logistic regression analysis, patient age was found to be
      a statistically significant risk factor (P = 0.007): the highest incidence was
      found in patients over 16 years of age (2.19%). At warmer times of year the
      incidence was higher (1.98%) than at colder times (1.63%). The resident surgeons
      caused a hemorrhage incidence of 1.75% and the consultant surgeons one of 1.84%.
      The incidence was significantly higher in male patients (2.2%) than in female
      patients (1.4%; P = 0.016). PRINCIPAL CONCLUSIONS: Our data show that whereas
      adenoidectomy can be safely performed as a one-day procedure, tonsillectomy
      complications due to postoperative hemorrhages might be avoided only if patients
      were to stay in hospital until postoperative day 15, which would clearly be
      impractical for economic, organizational and social reasons. A crucial factor for
      increasing the safety of this procedure is the provision of meticulous education
      and information for the patient and/or parents.

PMID- 18709522
TI  - Not carried away by a moonlight shadow: no evidence for associations between
      suicide occurrence and lunar phase among more than 65,000 suicide cases in
      Austria, 1970-2006.
AB  - OBJECTIVES: Belief in lunar effects on abnormal or deviant human behavior ("moon
      madness") is old, common, perpetuated by the media and notably widespread among
      health professionals, and may thus have public health consequences. This study
      investigated lunar effects on one particular outcome (completed suicide) for
      which the literature appears unsettled, owing to some recent reports with
      positive findings. METHODS: The timing of all 65,206 suicides (46,451 men; 18,755
      women) officially registered in Austria between 1970 and 2006 was analyzed with
      respect to the phases of the moon. This was the first such study based on
      national data conducted outside the USA, with the database comprising the second
      longest study period and the second-largest sample ever investigated in this
      subject area. RESULTS: Observed proportions of both male and female suicide
      occurrence did not deviate from expected proportions during the new, crescent,
      full, and decrescent moon quarters or from those expected for 3-day windows
      centered around new and full moon, relative to the interphase. Subgroup analysis
      (by sex and year), additionally conducted for demonstration purposes, yielded
      results conspicuously resembling those of related studies with positive findings;
      namely, sporadically emerging significant findings that were entirely absent in
      the overall analysis and directionally erratic, thus suggesting they were
      spurious (false positive). CONCLUSIONS: This large-sample evidence strongly
      suggests no lunar effects on the timing of completed suicide. Scattered previous
      evidence in support of such effects in all likelihood was spurious; that is, was
      due to statistical type 1 errors or erroneously taking calendrical periodicities
      of suicide occurrence that are real as evidence for lunar effects.

PMID- 18709523
TI  - Histopathology of the endoscopic esophagogastric junction in patients with
      gastroesophageal reflux disease.
AB  - BACKGROUND: Discrepancy exists between the endoscopic (rugal folds) and the
      histopathologic (oxyntic mucosa) definition of proximal stomach. We compared
      endoscopy and histopathology of the esophagogastric junction in patients with
      gastroesophageal reflux disease. METHODS: A total of 102 consecutive patients (60
      women) with gastroesophageal reflux disease prospectively underwent endoscopy
      including multilevel biopsy sampling at the level of the rise of rugal folds
      (level 0), and also 0.5 cm and 1.0 cm distal and 0.5 cm and > or = 1 cm proximal
      to this point. Columnar lined esophagus (CLE) was cataloged according to the
      histopathologic Paull-Chandrasoma classification and esophagitis according to the
      endoscopic Los Angeles classification. Hiatal hernia was diagnosed if the
      endoscopic rugal folds commenced > or = 2 cm above the diaphragm; competency of
      the esophagogastric valve was graded according to the Hill classification.
      RESULTS: All patients had histopathologic CLE with maximal presence at level 0
      (97%) and a decrease towards proximal and distal biopsy levels (level -0.5 cm,
      81%; level -1.0, 28%; level + 0.5 cm, 40%; level + 1.0 cm, 18%). Histopathologic
      CLE (distance between CLE-positive biopsy levels) was longer than endoscopic CLE
      (P < 0.001). All 19 patients with intestinal metaplasia (18.6%) were identified
      from 4-quadrant biopsies obtained at the squamocolumnar junction and at 0.5 cm
      distal from it. Persons with intestinal metaplasia were significantly older, had
      increased frequency of endoscopic hiatal hernia, higher Hill grade and presence
      of endoscopic CLE (P < 0.05); no significant difference was observed regarding
      sex, endoscopic esophagitis or length of endoscopic and histopathologic CLE (P >
      0.05). None of the patients had dysplasia or carcinoma. CONCLUSIONS: In patients
      with gastroesophageal reflux disease the esophagogastric junction cannot be
      identified by endoscopy but requires histopathology of multilevel biopsies. The
      squamocolumnar junction harbors the highest yield of intestinal metaplasia.

PMID- 18709524
TI  - Necrotizing cervical lymphadenopathy: Kikuchi-Fujimoto disease in a young male.
AB  - Kikuchi-Fujimoto disease (KFD) or histiocytic necrotizing lymphadenitis is a rare
      benign disease, more common in Japanese women, with only a few cases reported
      from other parts of the world. The pathogenesis is poorly understood. A 22-year
      old man noticed a node growth a month before his admittance. At first he noticed
      one enlarged node in the left axilla, later also the nodes on his neck and in his
      right axilla. Before that he had felt shivery and reported night sweats. Physical
      examination revealed bilateral enlarged (up to 2 cm) painful but not inflamed
      lymph nodes on the neck and in both axillae. The patient was diagnosed with KFD
      on histological examination of the nodes and on the basis of typical changes. No
      medical treatment was prescribed and the patient has been without symptoms for
      the past two years. The clinical picture of KFD is nonspecific and variable. Most
      patients complain of enlarged cervical nodes (up to 2 cm) accompanied by various
      symptoms (fever, malaise, night sweats, weight loss). The enlarged nodes, which
      are mobile, rarely appear in other locations. The only way of proving whether the
      disease is present or not is by histological examination of the node, which may
      show the following changes typical for KFD: paracortical necrotic foci,
      surrounded by histiocytic aggregates, irregular rounded eosinophilic areas of
      different sizes in the paracortex and cortex with the presence of numerous
      histiocytes, lymphocytes, immunoblasts, plasmacytoid monocytes and eosinophilic
      granulated cellular debris. Histiocytes had mostly turned into foamy macrophages.
      It is typical not to find epithelioid cells and neutrophil granulocytes in the
      necrotic centers. In particular, the disease needs to be distinguished from high
      grade lymphoma and SLE lymphadenitis. There is no specific medical treatment for
      KFD since the disease usually resolves spontaneously over four months. Disease
      recurrence or fatalities are unusual.

PMID- 18709525
TI  - Xanthogranulomatous epididymitis: clinical report and immunohistochemical
      analysis.
AB  - Xanthogranulomatous epididymitis is an uncommon non-neoplastic process with
      destruction of tissue and replacement by striking cellular infiltration of foamy
      macrophages, dense lymphocytes and plasma cells. We report on a 72-year-old man
      with a clinical history of inadequately treated arterial hypertension, who
      presented with a right scrotal mass associated with right scrotal pain for 10
      days. Physical examination revealed pyogenic discharge from the hyperemic and
      edematous scrotum, with normal body temperature. Testicular tumor markers were
      normal. Ultrasonography (US) of the right testis showed edematous scrotal layers
      and a heterogeneous area of poorly defined margins within the testis and
      epididymis. There was minimal hydrocele, and the right funiculus was of normal
      diameter with no edema or pathologic formation. The progression of clinical
      findings, inflammatory parameters, US and color Doppler US findings with negative
      testicular tumor markers indicated surgical treatment. After preoperative
      treatment, right orchiepididymectomy was performed. Histology confirmed the
      diagnosis of xanthogranulomatous epididymitis.

PMID- 18709526
TI  - [Diagnostic laboratory guideline for assessment of functional disorders and
      diseases of the thyroid gland].

PMID- 18709527
TI  - [Guidelines for prevention of venous thromboembolism in Austria].

PMID- 18709529
TI  - Role of nuclear IkappaB proteins in the regulation of host immune responses.
AB  - A variety of microbial components activate a transcription factor called nuclear
      factor-kappaB (NF-kappaB) that plays an essential role in the optimal activation
      of host immune systems. The transcriptional activity of NF-kappaB is tightly
      regulated at multiple steps in immune signaling pathways, because excessive
      activation is detrimental to the host. One mechanism to prevent NF-kappaB
      activation is mediated by cytoplasmic IkappaB family proteins. Although
      cytoplasmic IkappaBs interact with NF-kappaB subunits in the cytoplasm of
      unstimulated cells, IkappaBs are rapidly degraded on stimulation, allowing free
      NF-kappaB to translocate into the nucleus and activate the transcription of genes
      encoding various immune mediators. After the translocation of NF-kappaB from the
      cytoplasm to the nucleus, nuclear proteins that are structurally similar to
      cytoplasmic IkappaBs take part in the regulation of NF-kappaB transcriptional
      activity, as activators or inhibitors, by associating with NF-kappaB subunits.
      Therefore, the regulatory IkappaB-like nuclear molecules are described as
      "nuclear IkappaB proteins." In this review, the in vivo function of the nuclear
      IkappaB proteins, Bcl-3, IkappaBzeta, and IkappaBNS in the context of host immune
      responses and diseases will be discussed.

PMID- 18709530
TI  - The roles of prostanoids in infection and sickness behaviors.
AB  - A systemic infection in patients causes so-called sickness behaviors, such as
      fever generation, adrenocorticotropic hormone release, reduced locomotion, loss
      of social contact, anorexia, and increased sleep. As aspirin-like non-steroidal
      anti-inflammatory drugs alleviate most of these symptoms, the involvement of
      prostanoids in the generation of sickness behaviors has been strongly suggested.
      Prostanoids, consisting of prostaglandins (PGs) and thromboxanes (TXs), are a
      group of lipid mediators formed in response to various stimuli. They include
      PGD2, PGE2, PGF2alpha, PGI2, and TXA2. Immediately after synthesis, they are
      released outside the cells, and exert their actions by binding to a G-protein
      coupled rhodopsin-type receptor on the surface of target cells. There are eight
      types of prostanoid receptors: the PGD receptor, four subtypes of PGE receptor,
      the PGF receptor, the PGI receptor, and the TXA receptor. Recently, mice
      deficient in each of these prostanoid receptors were generated and the
      examination of these mice in various experimental disease models revealed the
      important roles of prostaglandin receptor signaling in various pathological
      processes. In this review, we describe several recent findings that have
      addressed the mechanisms underlying sickness behaviors and that have identified
      the critical roles of the signaling of each prostanoid receptor in the
      elicitation of the stress responses associated with these sickness behaviors.

PMID- 18709532
TI  - An outbreak of measles in Saitama City in 2007. What is the vaccination strategy
      to eliminate measles in Japan?
AB  - In the present study, to elucidate an outbreak of measles in Saitama City, Japan,
      we analyzed the data for all notified subjects with measles. According to an
      active surveillance program, a total of 464 subjects were notified in 2007. The
      clinical criteria for the diagnosis of measles were defined as at least 3 days of
      a generalized maculopapular rash; a fever of 38.0 degrees C or more; and cough,
      mucus, or pharyngitis. Two peaks according to age group were recognized: namely,
      children less than 2 years of age and adolescents from 15 to 19 years of age. The
      latter peak was associated with the period of time when the measles-mumps-rubella
      vaccine had become a social problem (40.9% of vaccinees and 41.6% of non
      vaccinees in this group). Japan is said to be a developing country regarding its
      measles vaccination strategy. In addition, no national program against measles
      has yet been established. Continuous efforts to increase immunization coverage
      are needed to interrupt indigenous measles transmission. The Japanese Ministry of
      Health, Labor and Welfare should therefore plan and implement a nationwide
      program to eliminate measles in Japan.

PMID- 18709531
TI  - The first nationwide surveillance of bacterial respiratory pathogens conducted by
      the Japanese Society of Chemotherapy. Part 1: a general view of antibacterial
      susceptibility.
AB  - The Japanese Society of Chemotherapy (JSC) conducted the first nationwide
      surveillance of bacterial respiratory pathogens during the period from January to
      August 2006. With the cooperation of 32 medical institutions throughout Japan, a
      total of 924 strains belonging to seven clinically relevant bacterial species
      were collected from adult patients with well-diagnosed respiratory tract
      infections (RTIs). Antimicrobial susceptibility testing of the 887 evaluable
      strains (205 Staphylococcus aureus, 200 Streptococcus pneumoniae, 9 Streptococcus
      pyogenes, 165 Haemophilus influenzae, 91 Moraxella catarrhalis, 74 Klebsiella
      pneumoniae, and 143 Pseudomonas aeruginosa) to 42 antibacterial agents was
      conducted at the Central Laboratory of the Research Center for Anti-infective
      Drugs of the Kitasato Institute, according to recommendations issued by the
      Clinical and Laboratory Standards Institute (CLSI). The antibacterial agents
      employed were 25 beta-lactams, three aminoglycosides, four macrolides (including
      one azalide and one ketolide), one lincosamide, one tetracycline, two
      glycopeptides, five fluoroquinolones, and one oxazolidinone. The incidence of
      methicillin-resistant S. aureus (MRSA) was 63.4%, and the incidences of
      penicillin-intermediately resistant S. pneumoniae (PISP) and penicillin-resistant
      S. pneumoniae (PRSP) were 35.0% and 4.0%, respectively. Among H. influenzae,
      21.2% of the strains were found to be beta-lactamase-nonproducing ampicillin
      (ABPC)-intermediately resistant (BLNAI), 29.1% to be beta-lactamase-nonproducing
      ABPC-resistant (BLNAR), and 4.8% to be beta-lactamaseproducing ABPC-resistant
      (BLPAR) strains. The incidence of extended-spectrum beta-lactamase-producing K.
      pneumoniae was 2.7% (2 of 74 strains). Three (2.1%) of the 143 P. aeruginosa
      strains were found to be metallo-beta-lactamaseproducing, including 1 (0.7%)
      multidrug-resistant strain. Through the nationwide surveillance, we obtained
      fundamental antimicrobial susceptibility data of clinically relevant bacterial
      pathogens in adult RTI to various antibacterial agents. These data will be a
      useful reference for future periodic surveillance studies, as well as for
      investigations to control antimicrobial-resistant pathogens.

PMID- 18709533
TI  - Evaluation of clinical dosage of gatifloxacin for respiratory tract infections in
      elderly patients based on pharmacokinetics/pharmacodynamics (PK/PD).
AB  - The efficacy and safety of gatifloxacin (GFLX) was evaluated for elderly patients
      with respiratory infections. Each patient received one-half (100 mg b.i.d.) or
      one-quarter (100 mg q.d.) of the conventional dosage of 200 mg b.i.d., after a
      tentative clinical dosage for GFLX was estimated based on the patient's age and
      body weight. The subjects were 34 patients aged 65 years or older with mild to
      moderate acute bronchitis, pneumonia, or chronic respiratory tract infections.
      The serum concentration of GFLX was measured for each patient, and population and
      pharmacokinetic (PPK) analysis was performed, using the Bayesian method, to
      calculate the AUC and maximum drug concentration (Cmax). The overall efficacy
      rate of GFLX for 33 patients was 87.9% (29/33 patients). GFLX was effective for
      75.0% (6/8 patients) in the 100-mg dosage group and 92.0% (23/25 patients) in the
      200-mg dosage group. The clinical efficacy was 90.0% (9/10 patients) for acute
      bronchitis, 86.7% (13/15 patients) for pneumonia, and 87.5% (7/8 patients) for
      chronic respiratory tract infections. The bacterial eradication rate was 85.7%
      (12/14 patients). No adverse events or laboratory abnormalities were observed.
      The AUC values were 11.2-37.5 microg.h/ml and 12.7-111 microg.h/ml for the 100-mg
      and 200-mg dosage groups, respectively, and the Cmax values were 1.28-3.02
      microg/ml and 0.72-6.35 microg/ml, respectively, for the two groups. These
      results suggest that the dosage of GFLX examined in this study is clinically
      useful in elderly patients aged 65 or older with acute bronchitis, pneumonia, or
      chronic respiratory tract infections. The results of PPK analysis with the dosage
      management also support the efficacy of GFLX.

PMID- 18709534
TI  - Retroperitoneal abscess perforating into the thoracic cavity in an
      immunocompromised host.
AB  - A 71-year-old man with a retroperitoneal abscess caused by a ureteral stone was
      successfully treated by retroperitoneal drainage. He was considered to be at high
      risk of infection because of his bedridden state (resulting from a post-cerebral
      infarction and malignant rheumatoid disease) and steroid administration for the
      rheumatoid disease. He also had an empyema adjacent to the retroperitoneal
      abscess. This was thought to be separate from the retroperitoneal abscess because
      it did not resolve after the retroperitoneal drainage. Thoracic cavity drainage
      was undertaken, after which the empyema disappeared. The drainage fluid contained
      pus, similar to the fluid from the retroperitoneal drainage. Escherichia coli
      organisms were cultured from both drainage fluids. There were no signs of
      recurrence on computed tomography (CT) imaging. In conclusion, we report a case
      of retroperitoneal abscess perforating into the thorax, successfully treated by
      retroperitoneal and thoracic cavity drainage in an immunocompromised host. CT was
      a very effective imaging modality for this diagnosis, and we recommend early
      drainage of abscess in immunocompromised patients.

PMID- 18709535
TI  - Influenza virus reactivation after remission with oseltamivir treatment in a
      patient undergoing nonmyeloablative bone marrow transplantation.
AB  - Influenza virus infection is an important cause of mortality after hematopoietic
      stem cell transplantation (HSCT). Although early diagnosis followed by standard
      therapy with oseltamivir is thought to prevent influenza complications in
      myeloablative bone marrow transplant recipients, the optimal duration of therapy
      in these patients has not yet been determined. We describe a case of influenza
      virus reactivation, after remission had been achieved with standard oseltamivir
      therapy, in a patient undergoing nonmyeloablative bone marrow transplantation
      (NMBMT). A rapid diagnostic test (RDT) for influenza virus detection was
      performed with the ESPLINE Influenza A&B-N kit, which is a rapid, readily
      available, and widely used approach enabling highly specific and sensitive
      detection, as well as monitoring, of influenza A and B viruses. However, our case
      shows that a very low viral load that is undetectable by this RDT can reactivate
      influenza during the early phase of NMBMT. Our case suggests that oseltamivir
      administration for influenza infection should be continued, at least until
      successful engraftment, to prevent virus reactivation. The patient must be
      frequently and carefully monitored even after the resolution of symptoms and the
      clearance of viruses from respiratory secretions. The decision to cease
      oseltamivir therapy safely can be assisted by negative results on reverse
      transcription polymerase chain reaction (RTPCR) analysis.

PMID- 18709536
TI  - Breakthrough cryptococcosis in a patient with systemic lupus erythematosus (SLE)
      receiving micafungin.
AB  - A 67-year-old woman with systemic lupus erythematosus (SLE) was admitted to our
      hospital because of lupus nephritis. Methylprednisolone minipulse therapy
      dramatically reduced her proteinuria; however; she then complained of general
      fatigue with low-grade fever. Radiological and culture studies revealed no
      infectious focus, but she was treated with meropenem and micafungin, considering
      her immunosuppressive state. Cytomegalovirus antigenemia was later determined and
      ganciclovir was added. She became afebrile, but complained of nausea and
      headache, and disorientation, without meningeal signs. Because a brain computed
      tomography (CT) scan showed no abnormality, we initially suspected some kind of
      drug interaction. Despite the discontinuation of all drugs, however, she still
      suffered from disturbance of consciousness. A lumbar puncture revealed yeast
      cells stained by India ink. A diagnosis of cryptococcal meningitis was confirmed.
      Though fluconazole and meropenem were administered, the patient died. Autopsy
      findings revealed disseminated cryptococcosis concomitant with pulmonary
      aspergillosis. Micafungin is a recently approved echinocandin-class antifungal
      agent that is now widely used in Japan because of its minimal toxicity and
      broadspectrum activity. However, such echinocandins have limited activity against
      a number of fungi. Indeed, breakthrough trichosporonosis is becoming a
      significant problem in patients with hematological malignancies who are receiving
      echinocandins. To the best of our knowledge, breakthrough cryptococcosis, as seen
      in our patient, has not been reported previously in patients who were receiving
      micafungin as an empiric antifungal therapy. This case highlights that
      cryptococcosis should be kept in mind as a possible breakthrough infection during
      the administration of echinocandins, especially in patients with cellular
      immunodeficiency.

PMID- 18709537
TI  - An asymptomatic case of pulmonary cryptococcosis with endobronchial polypoid
      lesions and bilateral infiltrative shadow.
AB  - A case of pulmonary cryptococcosis with focal endobronchial polypoid lesions is
      described. A 64-year-old woman consulted our hospital for further evaluation of
      an abnormal shadow on a chest radiograph. She had been prescribed corticosteroid
      for rheumatoid arthritis. Chest radiographs revealed an infiltrative shadow in
      the right lower and left middle and lower lung fields, and chest computed
      tomography (CT) revealed bilateral airspace consolidations and multiple nodules.
      A bronchoscopic finding revealed white polypoid lesions at the orifice of the
      posterior basal bronchus in the left lower lobe. Histopathological examination of
      transbronchial biopsy specimens demonstrated cryptococcal organisms. After
      fluconazole therapy for 4 months, the infiltrate had decreased in size and the
      bronchial polypoid lesions had disappeared.

PMID- 18709538
TI  - Disseminated cryptococcal infection with eosinophilia in a healthy person.
AB  - A 23-year-old man with no recent medical history was hospitalized complaining of
      high fever and cough. In addition to very marked eosinophilia, chest X-ray
      revealed extensive bronchovascular bundle thickening. Transbronchial lung biopsy
      (TBLB) showed moderate eosinophil infiltration. Cryptococcus neoformans infection
      was diagnosed, based on blood culture, cerebrospinal fluid culture, urine
      culture, and lung biopsy specimens. The eosinophilia was successfully alleviated
      by treatment for cryptococcal meningitis. Furthermore, cryptococcal sepsis
      resolved with amphotericin B and 5-flucytosine treatment. Eosinophilia commonly
      occurs following chronic Aspergillus infection, but the present case suggests the
      involvement of Cryptococcus in another mechanism for eosinophilia.

PMID- 18709539
TI  - An outbreak and isolation of drug-resistant Pseudomonas aeruginosa at Niigata
      University Hospital, Japan.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that causes disease in
      patients with impaired host defenses; it is often a cause of life-threatening
      nosocomial infection in critically ill and immunocompromised patients. An
      increase in the prevalence of multiple-drug-resistant Pseudomonas aeruginosa
      (MDRP) in hospitals is thus a worldwide problem. These increases are frequently
      related to the high selective pressure of antimicrobials commonly used in
      hospitalized patients, particularly extended-spectrum cephalosporins, beta
      lactamase-inhibitor combinations, carbapenems, fluoroquinolones, and
      aminoglycosides. We evaluated the clinical and microbiological characteristics of
      drug-resistant P. aeruginosa and MDRP strains that were isolated at Niigata
      University Hospital, Japan, from 2000 to 2004. We experienced an outbreak of MDRP
      in 2000, but colonization only was the main feature of the outbreak. Also, the
      isolation rate of MDRP has decreased since 2004; this reduction in the isolation
      rate seems to be a result of a move to newly built ward sections in 2001 and the
      establishment of an infection control team (ICT) in 2003.

PMID- 18709540
TI  - Development of breakpoints of carbapenems for intraabdominal infections based on
      pharmacokinetics and pharmacodynamics in peritoneal fluid.
AB  - This study aimed to develop breakpoints of carbapenems for intraabdominal
      infections, based on pharmacokinetics (PK) and pharmacodynamics (PD) at the
      target site. Imipenem, meropenem, and doripenem were each administered to 8-11
      patients before abdominal surgery, and venous blood and peritoneal fluid samples
      were obtained. The drug concentrations in plasma and peritoneal fluid were
      determined and analyzed using population pharmacokinetic modeling. Using the
      pharmacokinetic model parameters, a Monte Carlo simulation was performed to
      estimate the probabilities of attaining the bacteriostatic and bactericidal
      targets (20% and 40% of the time above the minimum inhibitory concentration
      [MIC], respectively) in peritoneal fluid. The bacteriostatic and bactericidal
      breakpoints were defined as the highest MIC values at which the bacteriostatic
      and bactericidal probabilities in peritoneal fluid were 80% or more. The
      breakpoints for the minimum and maximum approved dosages of each drug were
      identical for imipenem, meropenem, and doripenem, and some of these values varied
      with dosing interval and infusion time. Site-specific PK-PD-based breakpoints are
      proposed here for the first time, and should help us to select appropriate
      carbapenem regimens for intraabdominal infections.

PMID- 18709541
TI  - Variation in the attachment of Streptococcus pneumoniae to human pharyngeal
      epithelial cells after treatment with S-carboxymethylcysteine.
AB  - S-carboxymethylcysteine (S-CMC) is a mucolytic agent that can prevent respiratory
      infection by decreasing the attachment of respiratory pathogens to human
      pharyngeal epithelial cells (HPECs). Streptococcus pneumoniae is a major cause of
      respiratory infections. A previous study revealed that treatment of S. pneumoniae
      with S-CMC caused a decrease in the attachment of this bacterium to HPECs. In the
      present study we found that the effect of S-CMC varied according to hosts and
      strains. S-CMC treatment altered the surface structure of S. pneumoniae,
      resulting in a decrease of attachment, without affecting the virulence of the
      bacteria.

PMID- 18709543
TI  - Chromosome studies of European cyprinid fishes: interspecific homology of
      leuciscine cytotaxonomic marker-the largest subtelocentric chromosome pair as
      revealed by cross-species painting.
AB  - Leuciscine cyprinids possess a nearly invariant diploid number (2n = 50) with an
      extremely uniform karyotype comprising of 8 pairs of metacentric, 13-15 pairs of
      submetacentric and 2-4 pairs of subtelocentric (st) to acrocentric (a)
      chromosomes. The largest pair is characteristically an st/a element-the
      'leuciscine' cytotaxonomic marker. Previously, the interspecific homology of this
      chromosome pair could not be assessed owing to the inability to produce
      euchromatic or serial banding patterns. In the present study, we used laser
      microdissection (15-20 copies of the marker chromosome) to construct a whole
      chromosome probe (WCP) from the marker chromosome of the roach Rutilus rutilus to
      ascertain the interspecific homology of marker chromosomes by cross-species in
      situ hybridization. WCP was hybridized to chromosomes of widely distributed
      (Abramis brama, Alburnoides bipunctatus, Alburnus alburnus, Aspius aspius,
      Ballerus ballerus, B. sapa, Blicca bjoerkna, Chondrostoma nasus, Leucaspius
      delineatus, Leuciscus leuciscus, L. idus, R. rutilus, Scardinius
      erythrophthalmus, Squalius cephalus, and Vimba vimba) and Iberian endemic species
      (Achondrostoma oligolepis, Iberochondrostoma almacai, I. lusitanicum,
      Pseudochondrostoma duriense, S. alburnoides and S. pyrenaicus). Cross-species in
      situ hybridization to chromosomes of Phoxinus phoxinus, a representative of
      leuciscine sister lineage, showed the same pattern as in all of the leuciscins.
      The probe consistently hybridized to the distal part of the short arm of the
      marker chromosome, indicating sequence homology.

PMID- 18709544
TI  - Evaluation of (GTG)5-PCR for rapid identification of Streptococcus mutans.
AB  - Repetitive sequence-based polymerase chain reaction (PCR) fingerprinting using
      the (GTG)(5) primer was applied for fast screening of bacterial strains isolated
      from dental plaque of early childhood caries (ECC)-affected children. A group of
      29 Gram-positive bacteria was separated into a homogeneous cluster together with
      Streptococcus mutans reference strains and constituted an aberrant branch after
      the numerical analysis of (GTG)(5)-PCR fingerprints. Automated ribotyping with
      EcoRI restriction enzyme (RiboPrinter microbial characterization system) revealed
      high genetic heterogeneity among the tested group and proved to be a good tool
      for strain-typing purposes. Further characterization of the studied strains was
      achieved by extensive phenotyping and whole-cell protein fingerprinting and
      confirmed all the strains as S. mutans representatives. Obtained results showed
      rep-PCR fingerprinting with the (GTG)(5) primer to be a fast and reliable method
      for identification of S. mutans.

PMID- 18709545
TI  - Hyperlipidemia in glycogen storage disease type III: effect of age and metabolic
      control.
AB  - While the presence of hyperlipidaemia in glycogen storage disease (GSD) type Ia
      and Ib is generally accepted, few investigators have adequately assessed lipid
      profiles of GSD III in children, in whom the presence of hyperlipidaemia may be
      most prominent. We analysed the lipid profiles in 44 GSD III patients from 6
      months to 30 years of age. Hypertriglyceridaemia and hypercholesterolaemia were
      common in children younger than 3 years of age. Hypertriglyceridaemia correlated
      negatively with age, and may reflect increased severity of hypoglycaemia in this
      younger population. The presence of hyperlipidaemia during childhood in these
      patients identifies another GSD population that could be at risk for early
      cardiovascular disease (CVD). Consequently, the outcome of clinical trials
      investigating the vascular effect of hyperlipidaemia in GSD applies to types
      other than GSD I.

PMID- 18709546
TI  - Computerized adaptive test for patients with foot or ankle impairments produced
      valid and responsive measures of function.
AB  - OBJECTIVE: We tested the item response theory (IRT) model assumptions of the
      original item bank, and evaluated the practical and psychometric adequacy, of a
      computerized adaptive test (CAT) for patients with foot or ankle impairments
      seeking rehabilitation in outpatient therapy clinics. METHODS: Data from 10,287
      patients with foot or ankle impairments receiving outpatient physical therapy
      were analyzed. We first examined the unidimensionality, fit, and invariance IRT
      assumptions of the CAT item bank. Then we evaluated the efficiency of the CAT
      administration and construct validity and sensitivity of change of the foot/ankle
      CAT measure of lower-extremity functional status (FS). RESULTS: Results supported
      unidimensionality, model fit, and invariance of item parameters and patient
      ability estimates. On average, the CAT used seven items to produce precise
      estimates of FS that adequately covered the content range with negligible floor
      and ceiling effects. Patients who were older, had more chronic symptoms, had more
      surgeries, had more comorbidities, and did not exercise prior to receiving
      rehabilitation reported worse discharge FS. Seventy-one percent of patients
      obtained statistically significant change at follow-up. Change of 8 FS units
      (scale 0-100) represented minimal clinically important improvement. CONCLUSIONS:
      We concluded that the foot/ankle item bank met IRT assumptions and that the CAT
      FS measure was precise, valid, and responsive, supporting its use in routine
      clinical application.

PMID- 18709547
TI  - Adenosine A2A receptor blockade or deletion diminishes fibrocyte accumulation in
      the skin in a murine model of scleroderma, bleomycin-induced fibrosis.
AB  - Peripheral blood fibrocytes are a newly identified circulating leukocyte
      subpopulation that migrates into injured tissue where it may display fibroblast
      like properties and participate in wound healing and fibrosis of skin and other
      organs. Previous studies in our lab demonstrated that A(2A) receptor-deficient
      and A(2A) antagonist-treated mice were protected from developing bleomycin
      induced dermal fibrosis, thus the aim of this study was to determine whether the
      adenosine A(2A) receptor regulates recruitment of fibrocytes to the dermis in
      this bleomycin-induced model of dermal fibrosis. Sections of skin from normal
      mice and bleomycin-treated wild type, A(2A) knockout and A(2A) antagonist-treated
      mice were stained for Procollagen alpha2 Type I and CD34 and the double stained
      cells, fibrocytes, were counted in the tissue sections. There were more
      fibrocytes in the dermis of bleomycin-treated mice than normal mice and the
      increase was abrogated by deletion or blockade of adenosine A(2A) receptors.
      Because fibrocytes play a central role in tissue fibrosis these results suggest
      that diminished adenosine A(2A) receptor-mediated recruitment of fibrocytes into
      tissue may play a role in the pathogenesis of fibrosing diseases of the skin.
      Moreover, these results provide further evidence that adenosine A(2A) receptors
      may represent a new target for the treatment of such fibrosing diseases as
      scleroderma or nephrogenic fibrosing dermopathy.

PMID- 18709548
TI  - Anger, stress proliferation, and depressed mood among parents of children with
      ASD: a longitudinal replication.
AB  - Stress proliferation (the tendency for stressors to create additional stressors)
      has been suggested as an important contributor to depression among caregivers.
      The present study utilized longitudinal data from 90 parents of children with ASD
      to replicate and extend a prior cross-sectional study on stress proliferation by
      Benson (J Autism Develop Disord 36:685-695, 2006). Consistent with Benson's
      earlier findings, regression analyses indicated that stress proliferation
      mediated the effect of child symptom severity on parent depression. Parent anger
      was also found to mediate the effect of symptom severity on stress proliferation
      as well as the effect of stress proliferation on parent depression. Finally,
      informal social support was found to be related to decreased parent depressed
      mood over time. Implications of study findings are discussed.

PMID- 18709550
TI  - WITHDRAWN: Special Issue Honoring Dr. Elisabeth Bock.

PMID- 18709549
TI  - Consumer price sensitivity in Dutch health insurance.
AB  - AIM: To estimate the price sensitivity of consumer choice of health insurance
      firm. METHOD: Using paneldata of the flows of insured between pairs of Dutch
      sickness funds during the period 1993-2002, we estimate the sensitivity of these
      flows to differences in insurance premium. RESULTS: The price elasticity of
      residual demand for health insurance was low during the period 1993-2002,
      confirming earlier findings based on annual changes in market share. We find
      small but significant elasticities for basic insurance but insignificant
      elasticities for supplementary insurance. Young enrollees are more price
      sensitive than older enrollees. CONCLUSION: Competition was weak in the market
      for health insurance during the period under study. For the market-based reforms
      that are currently under way, this implies that measures to promote competition
      in the health insurance industry may be needed.

PMID- 18709552
TI  - Demonstration of neuron-glia transfer of precursors for GABA biosynthesis in a co
      culture system of dissociated mouse cerebral cortex.
AB  - Co-cultures of neurons and astrocytes were prepared from dissociated embryonic
      mouse cerebral cortex and cultured for 7 days. To investigate if these cultures
      may serve as a functional model system to study neuron-glia interaction with
      regard to GABA biosynthesis, the cells were incubated either in media containing
      [U-(13)C]glutamine (0.1, 0.3 and 0.5 mM) or 1 mM acetate plus 2.5 mM glucose plus
      1 mM lactate. In the latter case one of the 3 substrates was uniformly (13)C
      labeled. Cellular contents and (13)C labeling of glutamate, GABA, aspartate and
      glutamine were determined in the cells after an incubation period of 2.5 h. The
      GABA biosynthetic machinery exhibited the expected complexity with regard to
      metabolic compartmentation and involvement of TCA cycle activity as seen in other
      culture systems containing GABAergic neurons. Metabolism of acetate clearly
      demonstrated glial synthesis of glutamine and its transfer to the neuronal
      compartment. It is concluded that this co-culture system serves as a reliable
      model in which functional and pharmacological aspects of GABA biosynthesis can be
      investigated.

PMID- 18709553
TI  - Re-evaluation of histogenesis of gastric carcinomas: a comparative
      histopathological study between Helicobacter pylori-negative and H. pylori
      positive cases.
AB  - We histopathologically re-evaluated the histogenesis of gastric carcinomas from
      comparative studies between Helicobacter pylori-positive and H. pylori-negative
      cases using the gastritis score from the Updated Sydney System. The incidence of
      H. pylori-negative gastric carcinomas was 3.11% (12/386); they are likely to
      develop in the fundic gland mucosa, and show a gastric phenotype by mucin
      immunohistochemistry. Even in cases of completely gastric and predominantly
      gastric phenotypes, CDX2 protein was expressed in most cases (90.9% of pT1 and
      100% of pT2-3), indicating a possibility that intestinalization of carcinoma
      cells occurs independently of the background mucosa. Regarding the degree of
      gastritis of background mucosa surrounding 143 H. pylori-positive differentiated
      type adenocarcinomas, the mean score ranged from 1.497 to 1.713. Our data support
      the hypothesis that intestinal metaplasia is not a precancerous but a
      paracancerous lesion, and most gastric adenocarcinomas develop in mildly to
      moderately atrophic mucosa with H. pylori-infection, i.e., ongoing atrophy.

PMID- 18709554
TI  - Pathways to health risk exposure in adult film performers.
AB  - Despite being part of a large and legal industry in Los Angeles, little is known
      about adult film performers' exposure to health risks and when and how these
      risks might occur. The objective was to identify exposure to physical, mental,
      and social health risks and the pathways to such risks among adult film
      performers and to determine how risks differ between different types of
      performers, such as men and women. Semi-structured in-depth interviews were
      conducted with 18 female and ten male performers as well as two key informants
      from the industry. Performers and key informants were recruited through
      Protecting Adult Welfare, adult film venues, and snowball sampling. Performers
      engaged in risky health behaviors that included high-risk sexual acts that are
      unprotected, substance abuse, and body enhancement. They are exposed to physical
      trauma on the film set. Many entered and left the industry with financial
      insecurity and suffered from mental health problems. Women were more likely than
      men to be exposed to health risks. Adult film performers, especially women, are
      exposed to health risks that accumulate over time and that are not limited to
      sexually transmitted diseases.

PMID- 18709555
TI  - Estimating the prevalence of injection drug use among black and white adults in
      large U.S. metropolitan areas over time (1992--2002): estimation methods and
      prevalence trends.
AB  - No adequate data exist on patterns of injection drug use (IDU) prevalence over
      time within racial/ethnic groups in U.S. geographic areas. The absence of such
      prevalence data limits our understanding of the causes and consequences of IDU
      and hampers planning efforts for IDU-related interventions. Here, we (1) describe
      a method of estimating IDU prevalence among non-Hispanic Black and non-Hispanic
      White adult residents of 95 large U.S. metropolitan statistical areas (MSAs)
      annually over an 11-year period (1992--2002); (2) validate the resulting
      prevalence estimates; and (3) document temporal trends in these prevalence
      estimates. IDU prevalence estimates for Black adults were calculated in several
      steps: we (1) created estimates of the proportion of injectors who were Black in
      each MSA and year by analyzing databases documenting injectors' encounters with
      the healthcare system; (2) multiplied the resulting proportions by previously
      calculated estimates of the total number of injectors in each MSA and year (Brady
      et al., 2008); (3) divided the result by the number of Black adults living in
      each MSA each year; and (4) validated the resulting estimates by correlating them
      cross-sectionally with theoretically related constructs (Black- and White
      specific prevalences of drug-related mortality and of mortality from hepatitis
      C). We used parallel methods to estimate and validate White IDU prevalence. We
      analyzed trends in the resulting racial/ethnic-specific IDU prevalence estimates
      using measures of central tendency and hierarchical linear models (HLM). Black
      IDU prevalence declined from a median of 279 injectors per 10,000 adults in 1992
      to 156 injectors per 10,000 adults in 2002. IDU prevalence for White adults
      remained relatively flat over time (median values ranged between 86 and 97
      injectors per 10,000 adults). HLM analyses described similar trends and suggest
      that declines in Black IDU prevalence decelerated over time. Both sets of IDU
      estimates correlated cross-sectionally adequately with validators, suggesting
      that they have acceptable convergent validity (range for Black IDU prevalence
      validation: 0.27 < r < 0.61; range for White IDU prevalence: 0.38 < r < 0.80).
      These data give insight, for the first time, into IDU prevalence trends among
      Black adults and White adults in large U.S. MSAs. The decline seen here for Black
      adults may partially explain recent reductions in newly reported cases of IDU
      related HIV evident in surveillance data on this population. Declining Black IDU
      prevalence may have been produced by (1) high AIDS-related mortality rates among
      Black injectors in the 1990s, rates lowered by the advent of HAART; (2) reduced
      IDU incidence among Black drug users; and/or (3) MSA-level social processes
      (e.g., diminishing residential segregation). The stability of IDU prevalence
      among White adults between 1992 and 2002 may be a function of lower AIDS-related
      mortality rates in this population; relative stability (and perhaps increases in
      some MSAs) in initiating IDU among White drug users; and social processes. Future
      research should investigate the extent to which these racial/ethnic-specific IDU
      prevalence trends (1) explain, and are explained by, recent trends in IDU-related
      health outcomes, and (2) are determined by MSA-level social processes.

PMID- 18709556
TI  - Effect of thiolated polymers to textural and mucoadhesive properties of vaginal
      gel formulations prepared with polycarbophil and chitosan.
AB  - The aim of this study was to design and evaluate of mucoadhesive gel formulations
      for the vaginal application of clomiphene citrate (CLM) for local treatment of
      human papilloma virus (HPV) infections. Chitosan (CHI) and polycarbophil (PC)
      were covalently modified using the thioglycolic acid and L-cysteine,
      respectively. The formation of thiol conjugates of chitosan (CHI-TG) and
      polycarbophil (PC-CYS) were confirmed by FT-IR analysis and PC-CYS and CHI-TG
      were found to have 148.42 +/- 4.16 and 41.17 +/- 2.34 micromol of thiol groups
      per gram of polymer, respectively. One percent CLM gels were prepared by
      combination of various concentrations of PC and CHI with thiolated conjugates of
      these polymers. Hardness, compressibility, elasticity, adhesiveness and
      cohesiveness of the gels were measured by Texture profile analysis and the
      vaginal mucoadhesion was investigated by mucoadhesion test. The increasing in the
      amount of the thiol conjugates was found to enhance the elasticity, cohesiveness,
      adhesiveness and mucoadhesion of the gel formulations but not their hardness and
      compressibility when compared to gels prepared using their respective parent
      formulations. Slower release rate of CLM from gels was achieved when the polymer
      concentrations were increased in the gel formulations. PC and its thiol conjugate
      were found to prolong the release of CLM longer than 70 h unlike gel formulations
      prepared using CHI and its thiol conjugate which were able to release CLM up to
      12 h. Stability of CLM was preserved during the 3 month stability analysis under
      controlled room temperature and accelerated conditions.

PMID- 18709563
TI  - Mitochondrial DNA variant interactions modify breast cancer risk.
AB  - Interactions between mitochondrial deoxyribonucleic acid (mtDNA) variants and the
      risk of developing breast cancer were investigated using DNA samples collected
      from non-Jewish European American breast cancer patients and ethnically age
      matched female controls. Logistic regression was used to evaluate two-way
      interactions between 17 mtDNA variants. To control for multiple testing,
      empirical P values were calculated using permutation. Odds ratios (ORs) and
      corresponding 95% confidence intervals (CIs) were calculated to measure the
      contribution of variants in modifying the risk of developing breast cancer. A
      highly significant interaction was identified between variants 12308G and 10398G
      (empirical P value = 0.0028), with results suggesting these variants increase the
      risk of a woman developing breast cancer (OR = 3.03; 95% CI 1.53-6.11). Nominal
      significant P values were also observed for interactions between mtDNA variants
      709A and 16189C; 4216C and 10398G; 4216C and 16189C; 10398G and 16159C; 13368A
      and 16189C; and 14766T and 16519C. However, after adjusting for multiple testing,
      the P values did not remain significant. Although it is important to elucidate
      the main effect of mtDNA variants on the risk of developing breast cancer,
      understanding gene x gene interactions will give a greater knowledge of disease
      etiology and aid in interpreting a woman's risk of developing breast cancer.

PMID- 18709564
TI  - Prospects and challenges in using patient-reported outcomes in clinical practice.
AB  - BACKGROUND: Patient-reported measures include preferences and reports about care
      received, health behaviors, and outcomes of care (patient satisfaction and health
      related quality of life). These measures are a core aspect of health care, but
      there is much to be learned about how to use them to improve clinical practice.
      METHOD: We specify linkages among different patient-reported measures and focus
      upon the prospects and challenges for use of patient-reported outcomes in
      clinical practice. RESULTS: Patient-reported measures are important throughout
      the continuum of patient care. At the initial visit, patient-reported outcomes
      provide information about what is important to the patient, the patient's current
      behaviors, and the patient's baseline health-related quality of life. At
      subsequent visits, patient-reported outcomes help evaluate disease progression or
      regression as well as treatment effects. CONCLUSIONS: Patient-reported measures
      can help clinicians target interventions that will improve patient outcomes of
      care. However, there are a number of challenges in using patient-reported
      outcomes in clinical practice.

PMID- 18709566
TI  - Pain and u-shaped dose responses: occurrence, mechanisms, and clinical
      implications.
AB  - This article assesses pain within the context of the dose response. A substantial
      number of studies indicate that the dose response for pain-related endpoints is
      commonly biphasic, being independent of the type of biological model employed,
      endpoint measured, or agent tested. The quantitative features of the dose
      response are also remarkably consistent regardless of the receptor pathway that
      mediates the nociceptive response, indicating a likely downstream message
      convergence. These findings have important implications for drug discovery,
      development, and clinical evaluation.

PMID- 18709567
TI  - U-shaped dose response in behavioral pharmacology: historical foundations.
AB  - This article assesses the historical foundations of U-shaped dose-responses in
      behavioral pharmacology and toxicology with particular emphasis on schedules of
      reinforcement. Quantitative features of the drug dose response, which are
      consistent with the hormetic dose response model, are detailed along with
      possible mechanistic foundations to account for low-dose stimulation and high
      dose inhibition responses. The article provides a reinterpretation of the
      biphasic dose response in the fixed interval (FI) schedule of reinforcement.

PMID- 18709565
TI  - Constitutional mismatch repair-deficiency syndrome: have we so far seen only the
      tip of an iceberg?
AB  - Heterozygous mutations in one of the mismatch repair (MMR) genes MLH1, MSH2, MSH6
      and PMS2 cause the dominant adult cancer syndrome termed Lynch syndrome or
      hereditary non-polyposis colorectal cancer. During the past 10 years, some 35
      reports have delineated the phenotype of patients with biallelic inheritance of
      mutations in one of these MMR genes. The patients suffer from a condition that is
      characterised by the development of childhood cancers, mainly haematological
      malignancies and/or brain tumours, as well as early-onset colorectal cancers.
      Almost all patients also show signs reminiscent of neurofibromatosis type 1,
      mainly cafe au lait spots. Alluding to the underlying mechanism, this condition
      may be termed as "constitutional mismatch repair-deficiency (CMMR-D) syndrome".
      To give an overview of the current knowledge and its implications of this
      recessively inherited cancer syndrome we summarise here the genetic, clinical and
      pathological findings of the so far 78 reported patients of 46 families suffering
      from this syndrome.

PMID- 18709568
TI  - Addiction and dose response: the psychomotor stimulant theory of addiction
      reveals that hormetic dose responses are dominant.
AB  - In 1987 Wise and Bozarth proposed a psychomotor stimulant theory of addiction
      whose most consistent feature was enhanced forward (horizontal) locomotion. While
      controversial, the theory of Wise and Bozarth has had substantial impact on
      addiction behavior theory over the past two decades, being cited over 1,400
      times. The present assessment places the theoretical formulation of Wise and
      Bozarth (1987) within a dose-response framework. This analysis demonstrates that
      the psychomotor stimulant effects of addictive drugs routinely display biphasic
      dose-response relationships that are consistent with the quantitative features of
      the hormetic dose-response model. This is the case, regardless of addictive
      agent, animal model, and experimental protocol employed. Not only do these
      findings suggest an important role for the hormetic dose response model in the
      assessment of addictive behaviors, they also further extend the generalizability
      of the hormesis dose-response model concept within the biomedical sciences.

PMID- 18709569
TI  - The search for hormesis in the nervous system.

PMID- 18709570
TI  - Hormetic responses in neural systems: consideration, contexts, and caveats.
AB  - Dr. Edward Calabrese asserts that hormetic responses occur in neural systems, and
      provides ample review of evidence to support this claim. In this essay, we survey
      Dr. Calabrese's findings, illustrate the somewhat provocative premise of
      hormesis, and posit that while evidence suggests that amplification of low-dose
      effects are operative in neural systems, it is equally important to consider
      observations and claims of hormesis in greater detail, and framed within the
      "cultural" and epistemic contexts of science. We offer specific caveats to avoid
      the overgeneralization of findings, oversimplification of putative effects or
      mechanisms, and the dogmatic adherence to a restrictive methodologic orientation.
      Finally, we assert that any meaningful discussion of hormesis must be grounded to
      methodologic rigor, yet openness, and must allow for a self-critical and self
      revisionist epistemic approach. We attempt to show that the work presented by
      Calabrese takes a first and important step toward the initiation of dialectic,
      allows for the exchange of ideas, strives toward reconciliation of differences
      and the amelioration of error, and seeks intellectual synthesis.

PMID- 18709571
TI  - Peptides and hormesis.
AB  - Biology is replete with examples of hormesis, the term introduced and developed
      by Calabrese. The corresponding concept in the field of peptide research has been
      characterized as the inverted U-shaped dose-response relationship. The articles
      by Calabrese in this issue summarize the notable progress occurring in the past
      three decades. In contrast to the skepticism encountered when we introduced this
      concept for peptides in the early 1970s, hormesis is now becoming recognized as
      characteristic of many actions of these small proteins. Calabrese is performing a
      considerable service by his strong advocacy and promotion of the concept to a
      more general readership. Hopefully, hormesis will be routinely considered in the
      design of research projects and the discovery of pharmaceutical agents.

PMID- 18709573
TI  - Hormesis, adaptation, and the sandpile model.
AB  - Hormesis, characterized by stimulation (or inhibition) along some portion of the
      dose-response curve followed by its opposing action along some other portion of
      that curve, speaks to all those dose-response relationships characterized by a
      change in sign and reversal in direction of the curve as it progresses along the
      x axis (a nonmonotonic dose-response curve). Although this is better known in
      toxicology than in pharmacology, it behooves all clinicians to appreciate that if
      a particular dose of a medication is not efficacious, it does not necessarily
      follow that a higher dose will be more efficacious. The point of maximum
      stimulation (variable from individual to individual and variable within an
      individual over time) might be such that a lower dose of the medication would
      prove more therapeutic. Calabrese's hypothesis is that hormesis is a
      manifestation of the body's adaptive response to stress. This commentary
      emphasizes the importance of recognizing that such adaptations are always
      accomplished at some cost to the system in terms of its adaptation (nutrient and
      energetic) reserves. There is no gain without pain. Finally, the sandpile, a
      complex adaptive system whose evolution is characterized by iterative cycles of
      collapse and recovery, disruption and repair, challenge and adaptive
      reconstitution, may be a useful model for the cumulative impact over time of
      stress on the body, highlighting the complex nature of the body's responsiveness
      to varying degrees of stress.

PMID- 18709572
TI  - Awareness of hormesis will enhance future research in basic and applied
      neuroscience.
AB  - Hormesis is defined operationally as responses of cells or organisms to an
      exogenous or intrinsic factor (chemical, temperature, psychological challenge,
      etc.) in which the factor induces stimulatory or beneficial effects at low doses
      and inhibitory or adverse effects at high doses. The compendium of articles by
      Calabrese entitled "Neuroscience and Hormesis" provides a broad range of examples
      of neurobiological processes and responses to environmental factors that exhibit
      biphasic dose responses, the signature of hormesis. Nerve cell networks are the
      "first responders" to environmental challenges--they perceive the challenge and
      orchestrate coordinated adaptive responses that typically involve autonomic,
      neuroendocrine, and behavioral changes. In addition to direct adaptive responses
      of neurons to environmental stressors, cells subjected to a stressor produce and
      release molecules such as growth factors, cytokines, and hormones that alert
      adjacent and even distant cells to impending danger. The discoveries that some
      molecules (e.g., carbon monoxide and nitric oxide) and elements (e.g., selenium
      and iron) that are toxic at high doses play fundamental roles in cellular
      signaling or metabolism suggest that during evolution, organisms (and their
      nervous systems) co-opted environmental toxins and used them to their advantage.
      Neurons also respond adaptively to everyday stressors, including physical
      exercise, cognitive challenges, and dietary energy restriction, each of which
      activates pathways linked to the production of neurotrophic factors and cellular
      stress resistance proteins. The development of interventions that activate
      hormetic signaling pathways in neurons is a promising new approach for the
      preventation and treatment of a range of neurological disorders.

PMID- 18709574
TI  - Perceptions of living alone among older adult women.
AB  - This exploratory study examines older women's perceptions of living alone. Older
      adult women (N = 53) living alone were interviewed. Findings show tremendous
      variability in the perceptions of this sample. Whereas some women showed
      significant levels of loneliness and depression, many did not. Thirteen percent
      of the participants (n = 7) negatively perceived living alone, 49.1% (n = 26)
      neutrally perceived living alone, and 37.7% (n = 20) positively perceived living
      alone. Participants' most enjoyed aspects of living alone were being one's own
      boss/being independent (51%) and keeping one's own schedule (49%). Common
      responses for least enjoyable aspects of living alone were lack of companionship
      (62%), no one to help with housework (36%), and fear of falling or getting hurt
      (30%). Nurses should be aware that although some have perceived older adult women
      living alone as a vulnerable population, one cannot make assumptions based on
      living arrangements.

PMID- 18709575
TI  - Healthy eating during pregnancy: determinants and supportive strategies.
AB  - This article provides a review of the determinants of healthy eating in pregnancy
      by synthesizing current research findings and offers strategies to promote
      healthy eating during pregnancy. This article is guided by the ecological model
      for health promotion that suggests the determinants of healthy eating as
      intrapersonal or collective determinants of food choices and public policies that
      support healthy eating during pregnancy. Community health nurses can apply this
      model to gain insights into identifying gaps in practice and to prioritize action
      strategies to guide program development and interventions designed to support
      healthy eating by all pregnant women.

PMID- 18709576
TI  - Health needs of migrant and seasonal farmworkers.
AB  - Migrant and seasonal farmworkers (MSFW) are a vital component of the U.S.
      agricultural industry. Despite their important contributions, MSFW are known to
      be a marginalized population who live in poverty and have poor health indicators.
      The purpose of this study was to gain a fuller understanding of family
      composition, employment, migration patterns, health issues and service needs of
      MSFW in 3 counties in northwest Michigan. The participants were mainly migrant
      (63%), and men (55%) with an average age of 34.4 years. Educational levels of the
      sample were low, with 56% reporting 6th grade or below, and an additional 7%
      reporting no formal education. The majority was originally from Mexico (75%), and
      Spanish was the first language of 79% of the farmworkers represented in the
      survey. Work-related health problems and chronic illness were the most commonly
      perceived health problems and the most commonly requested service was dental.
      This study adds to the body of knowledge related to farm worker health needs and
      provides direction for the provision of appropriate health care to this
      population.

PMID- 18709577
TI  - A community health nursing approach to the problem of antibiotic over
      prescribing.
AB  - Antibiotic resistance due to over-prescribing is a critical problem for society.
      The purpose of this study was to examine the effect of a nurse-led quality
      assurance-based program designed to decrease inappropriate antibiotic prescribing
      rates in patients suffering from viral upper respiratory tract infections. The
      study was based in a network of community health centers in the Southeastern
      United States. A quasi-experimental design based upon pre- and postintervention
      measurement via chart reviews was utilized in the study. Both the pre- and
      postintervention chart reviews revealed high levels of inappropriate prescribing.
      Following intervention, no gross decrease in prescribing rates was noted.
      Qualitative differences were noted postintervention that included increased rates
      of prescriptions for delayed antibiotic therapy and decreased rates of reflexive
      prescription writing for farmers. Additionally, the results reflected the
      decreased use of broad-spectrum antibiotics after the intervention. Although the
      study utilized a limited sample, it shows promise for the use of quality
      assurance approaches in moderating inappropriate prescribing practices.

PMID- 18709578
TI  - Sixteenth annual National HIV Testing Day held on June 27, 2008.

PMID- 18709580
TI  - The best care for the right patient at the right time every time.

PMID- 18709581
TI  - Measuring cancer survival.

PMID- 18709582
TI  - Why don't people adopt recommended health behaviors?

PMID- 18709583
TI  - To expedite or not to expedite ...that is the question.

PMID- 18709584
TI  - Works-in-progress: guiding junior scientists through career development
      applications.
AB  - BACKGROUND: Career development awards are important to the professional careers
      of many junior scientists. Designed to launch researchers as independent
      scientists earlier in their careers, such grants release them from full schedules
      of teaching and clinical service, protecting their time for research and
      publishing. Yet few know how best to embark on this crucial endeavor. METHODS: We
      pilot tested a faculty-facilitated, biweekly working group for postdoctoral
      fellows and junior faculty preparing career development applications. Based on
      their needs and interests, sessions included didactic activities, structured
      panel discussions, identification of resources, and individual guidance. For
      those unable to attend regularly, e-mail kept them informed of information shared
      and lessons learned, as summarized by participants on a rotating basis. RESULTS:
      Although success in terms of funded applications is yet unknown, preliminary
      evaluation suggests high satisfaction among the participants. CONCLUSIONS:
      Ultimately, if successful, a low-cost, easy-to-administer working group approach
      such as this can add great value to any training program.

PMID- 18709585
TI  - Using Structured Clinical Instruction Modules (SCIM) in teaching palliative care
      to undergraduate medical students.
AB  - BACKGROUND: Student evaluation of the palliative care attachment at The
      University of Western Australia highlighted certain shortcomings. Methods. A 2
      hour Structured Clinical Instruction Module (SCIM) workshop was designed and
      implemented to address these issues. RESULTS: Preworkshop and postworkshop
      questionnaires showed a marked increase in self-rated competence and suggested
      this improvement was directly attributable to the workshop. A follow-up survey of
      a small number of students demonstrated this increase was sustained over time.
      CONCLUSIONS: SCIMs appear to be an effective instructional format in the small
      group setting. We covered a broad range of topics in a cost-effective manner and
      with minimal tutors and resources.

PMID- 18709586
TI  - Palliative radiotherapy knowledge among community family physicians and nurses.
AB  - BACKGROUND: Primary care physicians and nurses care for patients with advanced
      cancer and need to be aware of the role for palliative radiotherapy (PR).
      METHODS: We surveyed 250 family physicians, family medicine residents, and nurses
      attending oncology educational symposia to determine their knowledge of PR.
      RESULTS: The survey response rate was 59%, and most respondents (77%) were
      involved with the care of cancer patients. Many (58%) thought that their
      knowledge of PR was insufficient for their needs. Although bone metastasis and
      spinal cord compression were frequently recognized indications for PR, only 50%
      of other assessed indications for PR were correctly identified. Almost all
      respondents stated that they wanted to learn more about PR. CONCLUSIONS: More
      education regarding PR is required for primary care physicians and nurses caring
      for cancer patients.

PMID- 18709587
TI  - Opinions from ESL instructors and students about curricula on hepatitis B for use
      in immigrant communities.
AB  - BACKGROUND: Chinese immigrants in Canada have a disproportionately high risk for
      hepatitis B compared with non-Hispanic Whites. Hepatitis B is the leading cause
      of hepatocellular carcinoma among Asian immigrants to North America. English-as-a
      second-language (ESL) classes are an effective way of reaching newly immigrated
      individuals and are a potential channel for delivering health messages. METHODS:
      Using data from 6 focus groups among ESL instructors and students, we
      characterized perceptions about activities that are successfully used in ESL
      classrooms and strategies for delivering hepatitis B information. RESULTS.
      Instructors and students generally reported that activities that focused on
      speaking and listening skills and that addressed content relevant to students'
      daily lives were successful in the classroom. Instructors generally avoided
      material that was irrelevant or too difficult to understand. Focus group
      participants offered strategies for delivering hepatitis B information in ESL
      classrooms; these strategies included addressing symptoms and prevention and not
      singling out a specific population subgroup to avoid stigmatization. CONCLUSIONS:
      These findings might assist efforts to develop ESL curricula that target
      immigrant populations.

PMID- 18709588
TI  - Gender and online cancer support groups: issues facing male cancer patients.
AB  - BACKGROUND: Men are underrepresented in cancer support groups. They emphasize
      information seeking rather than emotional support and are less likely to express
      negative emotion critical for change. Three hypotheses were tested; men compared
      to women express fewer negative emotions, especially about their cancer, and men
      experience more fear and apprehension. METHOD: Four online professionally led
      groups were sampled. Assessments of emotions and fears used 3 text analysis
      programs. RESULTS: Women expressed more negative emotions. These differences were
      more pronounced when discussing their cancer. Men experienced greater
      anxiety/fear, which may explain their under representation. CONCLUSIONS: The dual
      dilemma of attracting men to support groups and directing them to emotional
      issues represents a challenge to health providers.

PMID- 18709589
TI  - Prostate cancer knowledge and screening attitudes of inner-city men.
AB  - BACKGROUND: We hypothesized that inner-city men are less knowledgeable about
      prostate health. METHODS: The prostate cancer knowledge and screening attitudes
      of 100 inner-city men (median age 62 +/- 11 years) seen at a urology clinic were
      assessed through a 30-item questionnaire administered before and after an
      educational intervention. RESULTS: Overall, intervention led to significantly
      better mean knowledge scores (47% before vs 80% after; P < .0001) but did not
      affect mean screening attitude scores. CONCLUSIONS: Although educational
      interventions might improve prostate cancer knowledge and screening rates among
      inner-city men, other approaches must also be considered.

PMID- 18709590
TI  - The effect of a school-based educational intervention on gender differences in
      reported family cancer history.
AB  - BACKGROUND: Gender differences in reported family cancer history could reduce the
      effectiveness of genetic screening for cancer risk. METHODS: We randomized 6
      schools to teach ninth graders about health genealogy through workshops or
      offered a delayed intervention. We assessed the effect of the intervention on
      reported family history of various cancers along with gender and side of the
      family from which cancer was reported. RESULTS: Girls reported more breast cancer
      in the family. Both sexes reported more maternal relatives with breast cancer.
      There were no treatment group effects. CONCLUSIONS: There are gender differences
      in reported family history of breast cancer.

PMID- 18709591
TI  - Quality of life after thyroid cancer: an assessment of patient needs and
      preferences for information and support.
AB  - BACKGROUND: In this article, we describe the quality of life and central
      information and support needs of people with thyroid cancer. We also describes
      patients' preferences for services to address their needs. This report may help
      patients to anticipate how thyroid cancer will affect them and inform physicians
      on useful ways to help address their patients' needs. METHODS: We collected data
      through a survey (n = 62) of people who had been treated for thyroid cancer.
      RESULTS: Most respondents indicated that quality of life was quite good, and most
      of their information needs were adequately addressed during routine care.
      However, respondents also indicated a desire for ongoing access to information,
      including information about lifestyle factors that might affect risk of
      recurrence, signs and symptoms of recurrence, and recent developments in thyroid
      cancer diagnostics and treatments. They also reported some unmet social and
      emotional support needs. Respondents reported a strong preference for gaining
      access to information through convenient resources such as the Internet.
      CONCLUSIONS: Patient care following thyroid cancer treatment could be improved by
      providing ongoing education about lifestyle factors related to cancer risk,
      disease surveillance, and resources for treating and coping with cancer. Health
      care providers should become familiar with local and Internet-based sources of
      information and support related to thyroid cancer to improve patient access to
      this information.

PMID- 18709592
TI  - Do gender-based disparities in authorship also exist in cancer palliative care? A
      15-year survey of the cancer palliative care literature.
AB  - BACKGROUND: Women physicians in the United States publish less than men and
      advance academically at a slower pace. Do such gender-based disparities also
      occur in cancer palliative care, a field in which women appear to hold a strong
      interest? METHODS: We undertook a detailed survey of the cancer palliative care
      literature. We selected 5 cancer palliative care journals on the basis of their
      high impact factors, and we assessed authorship for the years 1990, 1995, 2000,
      and 2005. We determined gender and highest educational degree for all US first
      and last authors. RESULTS: A total of 794 authors are the focus of this report.
      In 2005, 50% of first authors were women, but only 14% were women physicians.
      Similarly, 39% of senior authors were women during this year, but only 8% were
      women physicians. Over this 15-year period, no statistically significant trends
      were detected to indicate an increase in the number of women authors.
      CONCLUSIONS: These findings are sobering. Future efforts might focus on
      strategies to improve rates of authorship and, ultimately, improve rates of
      academic promotion for women interested in cancer palliative care.

PMID- 18709593
TI  - The talking cure: Schwartz Center Rounds foster compassion and collaboration.

PMID- 18709594
TI  - Does medical school instill lifelong learning.

PMID- 18709597
TI  - Phylogenetic signal, evolutionary process, and rate.
AB  - A recent advance in the phylogenetic comparative analysis of continuous traits
      has been explicit, model-based measurement of "phylogenetic signal" in data sets
      composed of observations collected from species related by a phylogenetic tree.
      Phylogenetic signal is a measure of the statistical dependence among species'
      trait values due to their phylogenetic relationships. Although phylogenetic
      signal is a measure of pattern (statistical dependence), there has nonetheless
      been a widespread propensity in the literature to attribute this pattern to
      aspects of the evolutionary process or rate. This may be due, in part, to the
      perception that high evolutionary rate necessarily results in low phylogenetic
      signal; and, conversely, that low evolutionary rate or stabilizing selection
      results in high phylogenetic signal (due to the resulting high resemblance
      between related species). In this study, we use individual-based numerical
      simulations on stochastic phylogenetic trees to clarify the relationship between
      phylogenetic signal, rate, and evolutionary process. Under the simplest model for
      quantitative trait evolution, homogeneous rate genetic drift, there is no
      relation between evolutionary rate and phylogenetic signal. For other
      circumstances, such as functional constraint, fluctuating selection, niche
      conservatism, and evolutionary heterogeneity, the relationship between process,
      rate, and phylogenetic signal is complex. For these reasons, we recommend against
      interpretations of evolutionary process or rate based on estimates of
      phylogenetic signal.

PMID- 18709598
TI  - On the distributions of bootstrap support and posterior distributions for a star
      tree.
AB  - Several authors have recently noted that when data are generated from a star
      topology, posterior probabilities can often be very large, even with arbitrarily
      large sequence lengths. This is counter to intuition, which suggests convergence
      to the limit of equal probability for each topology. Here the limiting
      distributions of bootstrap support and posterior probabilities are obtained for a
      four-taxon star tree. Theoretical results are given, providing confirmation that
      this counterintuitive phenomenon holds for both posterior probabilities and
      bootstrap support. For large samples the limiting results for posterior
      probabilities are the same regardless of the prior. With equal-length terminal
      edges, the limiting distribution is similar but not the same across different
      choices for the lengths of the edges. In contrast to previous results, the case
      of unequal lengths of terminal edges is considered. With two long edges, the
      posterior probability of the tree with long edges together tends to be much
      larger. Using the neighbor-joining algorithm, with equal edge lengths, the
      distribution of bootstrap support tends to be qualitatively comparable to
      posterior probabilities. As with posterior probabilities, when two of the edges
      are long, bootstrap support for the tree with long branches together tends to be
      large. The bias is less pronounced, however, as the distribution of bootstrap
      support gets close to uniform for this tree, whereas posterior probabilities are
      much more likely to be large. Our findings for maximum likelihood estimation are
      based entirely on simulation and in contrast suggest that bootstrap support tends
      to be fairly constant across edge-length choices.

PMID- 18709599
TI  - Assessing the performance of single-copy genes for recovering robust phylogenies.
AB  - Phylogenies involving nonmodel species are based on a few genes, mostly chosen
      following historical or practical criteria. Because gene trees are sometimes
      incongruent with species trees, the resulting phylogenies may not accurately
      reflect the evolutionary relationships among species. The increase in
      availability of genome sequences now provides large numbers of genes that could
      be used for building phylogenies. However, for practical reasons only a few genes
      can be sequenced for a wide range of species. Here we asked whether we can
      identify a few genes, among the single-copy genes common to most fungal genomes,
      that are sufficient for recovering accurate and well-supported phylogenies. Fungi
      represent a model group for phylogenomics because many complete fungal genomes
      are available. An automated procedure was developed to extract single-copy
      orthologous genes from complete fungal genomes using a Markov Clustering
      Algorithm (Tribe-MCL). Using 21 complete, publicly available fungal genomes with
      reliable protein predictions, 246 single-copy orthologous gene clusters were
      identified. We inferred the maximum likelihood trees using the individual
      orthologous sequences and constructed a reference tree from concatenated protein
      alignments. The topologies of the individual gene trees were compared to that of
      the reference tree using three different methods. The performance of individual
      genes in recovering the reference tree was highly variable. Gene size and the
      number of variable sites were highly correlated and significantly affected the
      performance of the genes, but the average substitution rate did not. Two genes
      recovered exactly the same topology as the reference tree, and when concatenated
      provided high bootstrap values. The genes typically used for fungal phylogenies
      did not perform well, which suggests that current fungal phylogenies based on
      these genes may not accurately reflect the evolutionary relationships among
      species. Analyses on subsets of species showed that the phylogenetic performance
      did not seem to depend strongly on the sample. We expect that the best-performing
      genes identified here will be very useful for phylogenetic studies of fungi, at
      least at a large taxonomic scale. Furthermore, we compare the method developed
      here for finding genes for building robust phylogenies with previous ones and we
      advocate that our method could be applied to other groups of organisms when more
      complete genomes are available.

PMID- 18709600
TI  - More taxa are not necessarily better for the reconstruction of ancestral
      character states.

PMID- 18709601
TI  - Phylogeny estimation and alignment via POY versus Clustal + PAUP*: a response to
      Ogden and Rosenberg (2007).

PMID- 18709604
TI  - Transthoracic echocardiography in adult patients--a proposal for documenting a
      standardized investigation.

PMID- 18709606
TI  - Quantification of colour Doppler activity in the wrist in patients with
      rheumatoid arthritis--the reliability of different methods for image selection
      and evaluation.
AB  - PURPOSE: The amount of colour Doppler activity in the inflamed synovium is used
      to quantify inflammatory activity. The measurements may vary due to image
      selection, quantification method, and point in cardiac cycle. This study
      investigated the test-retest reliability of ultrasound colour Doppler
      measurements in the wrist of patients with rheumatoid arthritis (RA) using
      different selection and quantification methods. MATERIALS AND METHODS: 14
      patients with RA had their wrist scanned twice by the same investigator with an
      interval of 30 minutes. The images for analysis were selected either by the
      anatomical position only or by the anatomical position with maximum colour
      Doppler activity. Subsequently, the amount of colour Doppler was measured in an
      area defined by either the synovial tissue or by specific anatomical structures
      surrounding the synovial tissue. RESULTS: The best test-retest reliability was
      obtained when the images were selected guided by colour Doppler and the
      subsequent quantification was done in an area defined by anatomical structures.
      With this method, the intra-class coefficient ICC (2.1) was 0.95 and the within
      subject SD (SW) was 0.017, indicating good reliability. In contrast, poor test
      retest reliability was found if the images were selected by anatomical position
      only and the quantification was done in an area defined by the synovial tissue
      (ICC [2.1] = 0.48 and SW = 0.049). CONCLUSION: The study showed that colour
      Doppler measurements are reliable if the images for analysis are selected by
      anatomical position in combination with colour Doppler activity and the
      subsequent analysis is performed in an area defined by anatomical structures.

PMID- 18709607
TI  - [Leipzig 2007--an internal retrospect].
AB  - Shortly before Dreilandertreffen 2008, the Leipzig group would like to review
      "Dreilandertreffen plus". The term "plus" is used because the 31(st)
      Dreilandertreffen was held together with the EFSUMB. What did this achieve? What
      does this mean for us in Davos? Review and evaluation of the contributions
      indicate a valuable enrichment due to the international participation but show a
      continued significant lack of large prospective studies to validate the clinical
      value of sonography. This issue cannot be corrected by efforts of the ultrasound
      associations to provide excellent and efficient advanced training at the
      Dreilandertreffen. The most important and striking contributions relate to
      contrast agent sonography and in particular to the differential diagnosis
      possibilities for liver tumors (DEGUM multicenter study), monitoring after
      interventional stent implantation for aortic aneurysms, and the monitoring of
      angiogenesis inhibition in the treatment of malignant tumors. Since these
      contributions are highly relevant and have the potential to be applied to
      guidelines, they require further scientific review and publication. The
      presidents of the three ultrasound associations in personal union with the
      presidents of the Dreilandertreffen should therefore place more importance on the
      scientific component of the Dreilandertreffen since the three countries are
      currently weak in this regard. Ultrasound diagnostics could play an important
      role in clinical health care research given the current exaggerated economic
      considerations in medicine. In addition, scientific work provides the basis for
      the future of the associations.

PMID- 18709608
TI  - Portal and splenic vein occlusion complicating Histoacryl injection therapy in
      bleeding gastric varices.

PMID- 18709609
TI  - Submucosal hemorrhage in the descending duodenum: endoscopic findings of acute
      severe pancreatitis.

PMID- 18709610
TI  - Successful treatment for hypopharyngeal cancer in a patient with superficial
      esophageal cancer by endoscopic submucosal dissection.

PMID- 18709611
TI  - Cerebral air embolism complicating esophagogastroduodenoscopy (EGD).

PMID- 18709612
TI  - Gastric ulcer following a thrombotic aneurysm of the splenic artery.

PMID- 18709613
TI  - Latex hand glove: a safe and convenient device for the endoscopic removal of
      foreign bodies.

PMID- 18709614
TI  - Perforation of the proximal esophagus treated with factor XIII.

PMID- 18709615
TI  - Endoscopic bougienage for a recurrent esophageal web using a small-caliber-tip
      transparent hood.

PMID- 18709616
TI  - Fracture of an esophageal stent: a rare but significant complication.

PMID- 18709617
TI  - Evaluation of a new flexible fiber CO2 laser for gastrointestinal cutting: NOTES
      and mucosectomy in a porcine model.

PMID- 18709618
TI  - Endoscopic retrograde cholangiography with contrast ultrasonography.

PMID- 18709619
TI  - Obscure gastrointestinal bleeding due to Meckel's diverticulum: unusual capsule
      endoscopic finding as polyp-like lesion.

PMID- 18709620
TI  - Early-stage laryngeal squamous cell carcinoma of the epiglottis treated by
      endoscopic submucosal dissection.

PMID- 18709621
TI  - Use of a transparent cap for endoscopic drainage of a pancreatic pseudocyst.

PMID- 18709622
TI  - Occult pancreatic head cancer in the setting of gallstone and common bile duct
      stones complicated by acute pancreatitis.

PMID- 18709623
TI  - Classic Kaposi's sarcoma and involvement of the small intestine as shown by
      capsule endoscopy.

PMID- 18709624
TI  - "Double jeopardy": twin problems associated with an esophageal self-expanding
      metal stent.

PMID- 18709625
TI  - [Pathophysiological aspects of smoking in pregnancy].
AB  - BACKGROUND: Smoking in pregnancy has, besides the effects on maternal health,
      well documented negative effects on pregnancy outcome, fetal growth and neonatal
      health. Most of the pathophysiological mechanisms of harm are not readily
      understood, often analogies to animal studies or mechanisms of disease known in
      adults are presumed to be effective in intrauterine life as well. MATERIALS AND
      METHODS: A Medline literature search was performed to retrieve articles on
      smoking, pregnancy and pathophysiology. Some aspects of pathophysiology are
      described here. RESULTS: Adaptation of the circulation to acute intrauterine
      stress is well documented in diseases of the trophoblast like the HELLP syndrome.
      Only few authors have focused their work on the unique physiological aspects of
      intrauterine life and growth in chronic exposure to nicotine and carbon monoxide.
      Some effects like disproportional growth impairment of the extremities vs. the
      head occur only in the intrauterine phase of life. Thus more scientific work is
      needed on the intrauterine effects of nicotine and carbon monoxide.

PMID- 18709626
TI  - [Smoking during pregnancy: rates, trends, risk factors].
AB  - Knowledge of the risks of smoking during pregnancy induces only part of the
      pregnant women to give up smoking. How many pregnant women in Germany smoke from
      the beginning to delivery, and what characterises these smokers, is the topic of
      this article. METHODS: Results from the German Mikrozensus, several national
      surveys, perinatal statistics and Euro-scip III are presented, compared, and
      assessed. Findings of our own studies conducted between 1999 and 2002 at the
      obstetric department and gynacological practices in Berlin allow an insight into
      the magnitude of "underreporting". RESULTS: In the ages 15-45 years 36-45 % of
      German women smoke, prevalence rates that probably are valid even for the
      beginning of pregnancy. While smoking prevalence in men has decreased during the
      last 20 years, there is an increasing trend in women. The prevalence is higher in
      pregnant women of low social status, living with smoking partners and those of
      German nationality. At most, half of the women give up smoking during pregnancy.
      Assuming an "underreporting" in pregnant women of at least one third, the
      prevalence of smoking up to delivery is 24 %. Although 76 % of the practicing
      gynacologists in Berlin feel responsible for smoking counselling, only 12 % are
      convinced that it is successful. CONCLUSIONS: A quarter of the pregnant women in
      Germany smoke through to delivery, which means that 150 000 newborns per year
      have been exposed to passive smoking in utero, and its long-term health effects,
      which is a national disaster.

PMID- 18709627
TI  - [Interventions for smoking cessation in pregnancy and postpartum. Modalities,
      efficacy, introduction to motivational interviewing and social-cognitive models
      for behaviour changes].
AB  - BACKGROUND: Interventions for smoking cessation in pregnancy are effective. But
      the effects are small. Cognitive-behavioural approaches and social support are
      more efficacious. Interventions for relapse prevention postpone relapse for six
      months. METHODS: Motivational interviewing serves as a practical basis for
      interventions. Social-cognitive models serve as basis to plan interventions.
      RESULTS: Our own results may be summarised as follows: 1) smoking in pregnancy
      and postpartum has a high priority with paediatricians and midwives; 2) also
      after delivery women express an interest in being counselled; 3) interventions
      increase the proportions of newly abstinent women and postpone relapse.
      CONCLUSIONS: The effects of such interventions are small and diminish between six
      and twelve months postpartum. With respect to population impact, it may be
      assumed that implementation in routine care will show sustained effects at the
      population level.

PMID- 18709628
TI  - [Neonatal results of prgenancies in overweight and obese mothers at the
      University of Wurzburg Gynaecology Clinic--a comparison of the years 1980 and
      2005].
AB  - BACKGROUND: The prevalence of overweight and obesity in pregnant women has
      increased during the last decades (in our examination period from 10.9 to 29.8
      %). Maternal obesity is a risk factor for pregnancy, delivery and the newborn.
      Does the neonatal outcome of pregnancies with maternal overweight and obesity in
      2005 differ from that in 1980? METHODS: All patients with a body mass index (BMI)
      > 25 kg / m (2) who delivered in 1980 (n = 130) and in 2005 (n = 392) at the
      University Hospital Wurzburg were evaluated retrospectively. The neonatal result
      of singletons born at term was studied (1980: n = 125; 2005: n = 315). RESULTS:
      The rates of macrosomia > 4500 g (5.6 vs. 1.3 %) and shoulder dystocia (4.8 vs.
      0.3 %) declined significantly. No significant differences were found regarding
      the mean newborn weight (3560 vs. 3508 g), weight percentile (55.5 vs. 56.4 %),
      length (51 cm), head size (35 cm), fetal distress (3.2 vs. 3.8 %), respiratory
      insufficiency (3.2 vs. 2.2 %), 5-min-Apgar (9.77 vs. 9.69) and arterial umbilical
      cord pH (7.27 vs. 7.26). Birth weight was not associated with the degree of
      obesity in 2005 compared to 1980. CONCLUSION: Despite the increasing prevalence
      and severity of obesity in pregnant women most parameters of neonatal outcome did
      not change. The observed relative rate of macrosomia and shoulder dystocia
      declined, but the case number of these complications is still relevant. Obviously
      obstetricians have responded appropriately to the changing risk profile.

PMID- 18709629
TI  - [Federal admission criteria for levels of perinatal care: definition,
      interpretation and first conclusions].
AB  - BACKGROUND: The outcome of high risk pregnancies is better in tertiary hospitals.
      The German government introduced levels of perinatal care only in 2006. The aim
      of this study was to investigate how many children are to be expected for each
      level, taking the possible width of interpretation of the admission criteria into
      account. MATERIALS AND METHODS: Perinatal quality assurance data from four German
      states (2005) were available. Based on the admission criteria used for level
      definitions, children were categorised into four different levels of care. To
      illustrate the possible width of interpretation of these admission criteria three
      analytical strategies were used. In addition, the distribution of children on
      different types of hospitals prior to the introduction of levels of care was
      analysed. RESULTS: Most deliveries (86-93 %) correspond to the lowest level, and
      only 1-5 % to the highest. Up to 15 % of children who should have been cared for
      in the highest level were born in hospitals with less than 500 annual deliveries.
      Among the neonates with risk profiles corresponding to the admission criteria for
      the two highest levels, up to 30 % were born in delivery units without NICUs. The
      majority (83 %) of attached NICUs had low caseloads (< 50 neonates < 1500 g /
      year). CONCLUSION: Most children fulfil the admission criteria for the lowest
      level of care whereas the need for specialised centres is rather low. Optimising
      the place of birth appropriately remains a challenge. Definition of levels of
      care based on admission criteria are difficult to implement due to a broad
      variety of interpretations.

PMID- 18709630
TI  - [Premature birth at the boundary of infant viability].

PMID- 18709631
TI  - [New version of recommendation no. 024-019 "premature birth at the boundary of
      infant viability"].

PMID- 18709632
TI  - [EuroNeoStat: a European information system on the outcomes of care for very-low
      birth-weight infants (< 1500 g)].
AB  - BACKGROUND: Prematurity rates are increasing throughout the world. Despite an
      overall rather small percentage of very low birth weight infants (VLBWI), which
      is approx. 1-2 % in most countries, these infants contribute significantly to
      morbidity and neonatal and infant mortality rates. METHODS: EuroNeoStat was
      initiated as an European information system on the outcomes of VLBWI to monitor
      and improve the care of these infants throughout Europe. EuroNeoStat includes an
      initiative, called EuroNeoSafe, to promote the safety of these high risk preterm
      infants. Perinatal and neonatal data from VLBWI is collected without using data
      that identify individuals or institutions. These data is analyzed at the
      coordination center in Bilbao. All institutions taking care on VLBWI in Europe
      can participate in this network and will be able to compare their own outcome
      data with other institutions from the network. Information on EuroNeoStat and the
      current data set is available on www.euroneostat.org. CONCLUSION: Successful
      initiatives aiming at improving outcomes in perinatal and neonatal care require
      collaborative networking, an attitude of constructive criticism and thorough
      comparative analysis of the outcomes and incidents in the health-care process.

PMID- 18709634
TI  - In situ localisation and quantification of surfactins in a Bacillus subtilis
      swarming community by imaging mass spectrometry.
AB  - Surfactins are a family of heptacyclopeptides in which the C-terminal carbonyl is
      linked with the beta-hydroxy group of a fatty acid acylating the N-terminal
      function of a glutamic acid residue. The fatty acyl chain is 12-16 carbon atoms
      long. These compounds, which are secreted by the Gram-positive bacterium Bacillus
      subtilis in stationary phase in liquid cultures, play an important role in
      swarming communities on the surface of agar media in the formation of dendritic
      patterns. TOF secondary ion MS (TOF-SIMS) imaging was used to map surfactins
      within 16-17 h swarming patterns, with a 2 mum spatial resolution. Surfactins
      were mainly located in the central mother colony (the site of initial
      inoculation), in a 'ring' surrounding the pattern and along the edges of the
      dendrites. In the mother colony and the interior of the dendrites, surfactins
      with shorter chain lengths are present, whereas in the ring surrounding the swarm
      community and between dendrites, surfactins with longer fatty acyl chain lengths
      were found. A quantitative analysis by MALDI-TOF MS showed a concentration
      gradient of surfactin from the mother colony to the periphery. The concentration
      of surfactin was approximately 400 pmol/mL in the mother colony and approximately
      10 pmol/mL at the base of the dendrites, decreasing to 2 pmol/mL at their tips.

PMID- 18709637
TI  - Stress perception and commuting.
AB  - This paper analyzes the determinants of the perceived stress level of workers
      with a special focus on the effects of commuting, while controlling for personal
      and work-related characteristics. Using ordered logistic regression we find that
      several dimensions of the commuting situation, such as impedance, control and
      predictability of commuting, significantly influence the perceived stress level.
      Therefore, stress and stress-related health problems should be taken into
      consideration when analyzing the economic costs of commuting.

PMID- 18709638
TI  - Comparison of the antiobesity effects of the protopanaxadiol- and
      protopanaxatriol-type saponins of red ginseng.
AB  - A previous study demonstrated that ginseng crude saponins prevent obesity induced
      by a high-fat diet in rats. Ginseng crude saponins are known to contain a variety
      of bioactive saponins. The present study investigated and compared the
      antiobesity activity of protopanaxadiol (PD) and protopanaxatriol (PT) type
      saponins, major active compounds isolated from crude saponins. Male 4-week-old
      Sprague-Dawley rats were fed with normal diet (N) or high-fat diet (HF). After 5
      weeks, the HF diet group was subdivided into the control HF diet, HF diet-PD and
      HF diet-PT group (50 mg/kg/day, 3 weeks, i.p.). Treatment with PD and PT in the
      HF diet group reduced the body weight, total food intake, fat contents, serum
      total cholesterol and leptin to levels equal to or below the N diet group. The
      hypothalamic expression of orexigenic neuropeptide Y was significantly decreased
      with PD or PT treatment, whereas that of anorexigenic cholecystokinin was
      increased, compared with the control HF diet group. In addition, PD type saponins
      had more potent antiobesity properties than PT saponins, indicating that PD-type
      saponins are the major components contributing to the antiobesity activities of
      ginseng crude saponins. The results suggest that the antiobesity activity of PD
      and PT type saponins may result from inhibiting energy gain, normalizing
      hypothalamic neuropeptides and serum biochemicals related to the control of
      obesity.

PMID- 18709636
TI  - Investing time in health: do socioeconomically disadvantaged patients spend more
      or less extra time on diabetes self-care?
AB  - BACKGROUND: Research on self-care for chronic disease has not examined time
      requirements. Translating Research into Action for Diabetes (TRIAD), a multi-site
      study of managed care patients with diabetes, is among the first to assess self
      care time. OBJECTIVE: To examine associations between socioeconomic position and
      extra time patients spend on foot care, shopping/cooking, and exercise due to
      diabetes. DATA: Eleven thousand nine hundred and twenty-seven patient surveys
      from 2000 to 2001. METHODS: Bayesian two-part models were used to estimate
      associations of self-reported extra time spent on self-care with race/ethnicity,
      education, and income, controlling for demographic and clinical characteristics.
      RESULTS: Proportions of patients spending no extra time on foot care,
      shopping/cooking, and exercise were, respectively, 37, 52, and 31%. Extra time
      spent on foot care and shopping/cooking was greater among racial/ethnic
      minorities, less-educated and lower-income patients. For example, African
      Americans were about 10 percentage points more likely to report spending extra
      time on foot care than whites and extra time spent was about 3 min more per day.
      DISCUSSION: Extra time spent on self-care was greater for socioeconomically
      disadvantaged patients than for advantaged patients, perhaps because their
      perceived opportunity cost of time is lower or they cannot afford substitutes.
      Our findings suggest that poorly controlled diabetes risk factors among
      disadvantaged populations may not be attributable to self-care practices.

PMID- 18709639
TI  - Highly sensitive detection of early-stage pancreatic cancer by multimodal near
      infrared molecular imaging in living mice.
AB  - Pancreatic cancer is a serious disease with poor patient outcome, often as a
      consequence of late diagnosis in advanced stages. This is in large part due to
      the lack of diagnostic tools for early detection. To address this deficiency, we
      have investigated novel molecular near-infrared fluorescent (NIRF) in vivo
      imaging techniques in clinically relevant mouse models of pancreatic cancer.
      Genome wide gene expression profiling was used to identify cathepsin cystein
      proteases and matrix metalloproteinases (MMP) as targets for NIRF imaging.
      Appropriate protease activatable probes were evaluated for detection of early
      stage pancreatic cancer in mice with orthotopically implanted pancreatic cancer
      cell lines. Mice with pancreatitis served as controls. Whole body in vivo NIRF
      imaging using activatable cathepsin sensitive probes specifically detected
      pancreatic tumors as small as 1-2 mm diameter. Imaging of MMP activity
      demonstrated high specificity for MMP positive tumors. Intravital flexible
      confocal fluorescence lasermicroscopy of protease activity enabled specific
      detection of pancreatic tumors at the cellular level. Importantly, topical
      application of NIRF-probes markedly reduced background without altering signal
      intensity. Taken together, macroscopic and confocal lasermicroscopic molecular in
      vivo imaging of protease activity is highly sensitive, specific and allows
      discrimination between normal pancreatic tissue, inflammation and pancreatic
      cancer. Translation of this approach to the clinic could significantly improve
      endoscopic and laparoscopic detection of early-stage pancreatic cancer.

PMID- 18709640
TI  - Modification of the inverse association between dietary vitamin D intake and
      colorectal cancer risk by a FokI variant supports a chemoprotective action of
      Vitamin D intake mediated through VDR binding.
AB  - Vitamin D has anticarcinogenic properties and might influence colorectal cancer
      (CRC) risk, but the epidemiological evidence is inconsistent. Many mechanisms of
      action for vitamin D have been proposed, with some of them initiating via its
      binding to the vitamin D receptor (VDR). Using a large Scottish case-control
      study, we investigated (i) main associations between CRC, vitamin D and calcium
      dietary intake and 4 VDR single nucleotide polymorphisms (rs10735810, rs1544410,
      rs11568820, rs7975232) and (ii) interaction associations between the VDR
      variants, vitamin D and calcium intakes. Inverse and dose-dependent associations
      were found between CRC risk, dietary [Odds ratio (OR) = 0.77, 95% confidence
      intervals (CI) 0.63, 0.92, p-trend = 0.012] and total vitamin D (OR = 0.80, 95%
      CI 0.65, 0.98, p-trend = 0.014) intake in multivariable-adjusted logistic
      regression models, whereas neither calcium intake nor any of the VDR variants
      were associated with CRC. Additionally, we observed statistically significant
      interactions (case-control, case-only designs) between vitamin D and calcium
      intake and rs10735810 (p-interaction 0.02, 0.006, respectively). We conducted
      meta-analyses of cohort, case-control and serum studies that also showed an
      inverse association between dietary vitamin D intake and CRC (serum studies:
      combined OR = 0.70, 95% CI 0.56, 0.87). The evidence of interaction we report
      here further supports the inverse association between vitamin D mediated through
      binding to the VDR.

PMID- 18709641
TI  - Four potential biomarkers as prognostic factors in stage III serous ovarian
      adenocarcinomas.
AB  - The mortality rate for patients with ovarian carcinomas is high and the available
      prognostic factors are insufficient. The use of biomarkers may contribute to
      better prediction and survival for these patients. We aimed to study the gene and
      protein expressions for 7 potential biomarkers, to determine if it is possible to
      use them as prognostic factors. Genes selected from our previous microarray
      analysis (2006), CLU, ITGB3, TACC1, MUC5B, CAPG, PRAME and TROAP, were analyzed
      in 19 of the tumors with quantitative real-time polymerase chain reaction (QPCR).
      We found that CLU and ITGB3 were more expressed in tumors from survivors and
      PRAME and CAPG were more expressed in tumors from deceased patients. None of the
      other 3 genes were significantly differently expressed. The protein expressions
      of CLU, ITGB3, PRAME and CAPG were analyzed in 43 of the tumors with western blot
      for semiquantitative analysis. We established that the mRNA and protein
      expressions correlated and that all 4 proteins were significantly differently
      expressed. Further, immunohistochemistry (IHC) was used to localize the
      expression of the proteins in the tumor samples. According to our results, the 4
      biomarkers CLU, ITGB3, PRAME and CAPG may be used as prognostic factors for
      patients with stage III serous ovarian adenocarcinomas.

PMID- 18709643
TI  - Loss of Drop1 expression already at early tumor stages in a wide range of human
      carcinomas.
AB  - In a study on gene deregulation in ovarian carcinoma we found a mRNA coding for a
      350 kDa protein, Drop1, to be downregulated 20- to 180-fold in the majority of
      ovarian and mammary carcinomas. The mRNA is encoded by a set of exons in the 5'
      region of the SYNE1 gene. Immunohistochemical staining for Drop1 protein by a
      specific monoclonal antibody corresponds to the pattern seen for the mRNA. cDNA
      arrays of matched pairs of tumor and normal tissue and in situ hybridizations
      confirmed the drastic loss of Drop1 mRNA as a common feature in uterus, cervix,
      kidney, lung, thyroid and pancreas carcinomas, already at early tumor stages and
      in all metastases. Two-hybrid studies suggest a role of this deficiency in the
      malignant progression of epithelial tumors.

PMID- 18709642
TI  - Nucleotide excision repair genes and risk of lung cancer among San Francisco Bay
      Area Latinos and African Americans.
AB  - Few studies on the association between nucleotide excision repair (NER) variants
      and lung cancer risk have included Latinos and African Americans. We examine
      variants in 6 NER genes (ERCC2, ERCC4, ERCC5, LIG1, RAD23B and XPC) in
      association with primary lung cancer risk among 113 Latino and 255 African
      American subjects newly diagnosed with primary lung cancer from 1998 to 2003 in
      the San Francisco Bay Area and 579 healthy controls (299 Latinos and 280 African
      Americans). Individual single nucleotide polymorphism and haplotype analyses,
      multifactor dimensionality reduction (MDR) and principal components analysis
      (PCA) were performed to assess the association between 6 genes in the NER pathway
      and lung cancer risk. Among Latinos, ERCC2 haplotype CGA (rs238406, rs11878644,
      rs6966) was associated with reduced lung cancer risk [odds ratio (OR) of 0.65 and
      95% confidence interval (CI): 0.44-0.97], especially among nonsmokers (OR = 0.29;
      95% CI: 0.12-0.67). From MDR analysis, in Latinos, smoking and 3 SNPs (ERCC2
      rs171140, ERCC5 rs17655 and LIG1 rs20581) together had a prediction accuracy of
      67.4% (p = 0.001) for lung cancer. Among African Americans, His/His genotype of
      ERCC5 His1104Asp (rs17655) was associated with increased lung cancer risk (OR =
      1.78; 95% CI: 1.09-2.91), and LIG1 haplotype GGGAA (rs20581, rs156641, rs3730931,
      rs20579 and rs439132) was associated with reduced lung cancer risk (OR = 0.61;
      95% CI: 0.42-0.88). Our study suggests different elements of the NER pathway may
      be important in the different ethnic groups resulting either from different
      linkage relationship, genetic backgrounds and/or exposure histories.

PMID- 18709644
TI  - Ebselen sensitizes glioblastoma cells to Tumor Necrosis Factor (TNFalpha)-induced
      apoptosis through two distinct pathways involving NF-kappaB downregulation and
      Fas-mediated formation of death inducing signaling complex.
AB  - Resistance to tumor necrosis factor (TNFalpha)-induced apoptosis in various
      cancer cells has been attributed to the activation of the transcription factor NF
      kappaB. Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]one)-a selenoorganic compound
      is known to prevent TNFalpha-mediated NF-kappaB activity. As glioblastoma are
      resistant to the cytotoxic effect of TNFalpha, we investigated the potential of
      Ebselen in sensitizing glioma cells to TNFalpha-induced apoptosis. Although
      treatment with Ebselen reduced viability of glioma cells, cotreatment with
      TNFalpha enhanced apoptosis further through alteration of TNFalpha-mediated
      signaling pathways. Sensitization of TNFalpha activated glioma cells to apoptosis
      by Ebselen involved 2 pathways: (i) abrogation of TNFalpha induced NF-kappaB
      activation and (ii) induction of Fas-associated death inducing signaling complex
      (DISC) formation. Ebselen inhibited the prosurvival pathway mediated by NF-kappaB
      by altering the association of TNF receptor associated factor 2 (TRAF2) with
      TNFalpha receptor associated death domain (TRADD) in the TNFR1-TRADD-TRAF2
      complex -an interaction crucial for mediating NF-kappaB activity. Ebselen also
      induced the formation of DISC involving Fas, Fas-associated death domain (FADD)
      and active caspase 8 to transduce apoptotic signals in situations where NF-kappaB
      function was inhibited. Cotreatment with Ebselen and TNFalpha induced G2/M phase
      arrest in cell cycle and modulated the expression of molecules involved in cell
      cycle progression. These results raise the possibility of overcoming resistance
      to TNFalpha-induced apoptosis by cotreatment with organoselenium Ebselen as a
      strategy to kill glioma cells.

PMID- 18709645
TI  - Frequent promoter hypermethylation and transcriptional downregulation of the
      NDRG2 gene at 14q11.2 in primary glioblastoma.
AB  - The N-myc downstream-regulated gene 2 (NDRG2) at 14q11.2 has been reported to be
      downregulated in glioblastoma, and NDRG2 overexpression represses glioblastoma
      cell proliferation in vitro (Deng et al., Int J Cancer 2003;106;342-7). To
      further address the role of NDRG2 as a candidate tumor suppressor in human
      gliomas, we analyzed 67 astrocytic tumors (10 diffuse astrocytomas, 11 anaplastic
      astrocytomas, 34 primary glioblastomas and 12 secondary glioblastomas) for NDRG2
      gene mutation, promoter methylation and expression at the mRNA and protein
      levels. Using real-time reverse transcription PCR analysis, we found decreased
      NDRG2 mRNA levels in primary glioblastomas as compared to diffuse and anaplastic
      astrocytomas. Similarly, immunohistochemistry revealed low or absent NDRG2
      protein expression in primary glioblastomas. Mutational analysis of the entire
      NDRG2 coding sequence did not reveal any tumor-associated DNA sequence
      alterations. However, sequencing of sodium bisulfite-modified DNA identified
      hypermethylation of the NDRG2 promoter region in 21 of 34 primary glioblastomas
      (62%). Moreover, NDRG2 promoter hypermethylation was associated with decreased
      NDRG2 mRNA expression. In contrast to primary glioblastomas, NDRG2 promoter
      hypermethylation was detected in only 1 of 11 anaplastic astrocytomas (9%) and
      was absent in 10 diffuse astrocytomas and 12 secondary glioblastomas. Taken
      together, our data support NDRG2 as a candidate tumor suppressor gene that is
      epigenetically silenced in the majority of primary glioblastomas, but not in
      lower grade astrocytomas and secondary glioblastomas.

PMID- 18709646
TI  - Ultrastructural and antigenic properties of neural stem cells and their progeny
      in adult rat subventricular zone.
AB  - Neural stem cells (NSCs) in the subventricular zone (SVZ) continuously generate
      olfactory bulb interneurons in the adult rodent brain. Based on their
      ultrastructural and antigenic properties, NSCs, transient amplifying precursor
      cells, and neuroblasts (B, C, and A cells, respectively) have been distinguished
      in mouse SVZ. Here, we aimed to identify these cell types in rat SVZ
      ultrastructurally and at the light microscopy level, and to determine the
      antigenic properties of each cell type using gold and fluorescence
      immunolabeling. We found astrocytes with single cilia (NSCs, correspond to B
      cells) and neuroblasts (A cells). We also observed mitotic cells, ependymal
      cells, displaced ependymal cells, and mature astrocytes. In contrast, transient
      amplifying precursor cells (C cells) were not detected. The NSCs and neuroblasts
      had epidermal growth factor receptor (EGFR) and platelet-derived growth factor
      receptor alpha (PDGFRalpha) expressed on the ciliary apparatus and were the only
      cell types incorporating the proliferation marker BrdU. Throughout mitosis, EGFR
      and PDGFRalpha were associated with the microtubule of the mitotic spindle.
      Ependymal and displaced ependymal cells also expressed EGFR and PDGFRalpha on
      their cilia but did not incorporate BrdU. Our findings indicate that the NSCs in
      adult rat SVZ give rise directly to neuroblasts. During mitosis, the NSCs
      disassemble the primary cilium and symmetrically distribute EGFR and PDGFRalpha
      among their progeny.

PMID- 18709647
TI  - The localization and non-genomic function of the membrane-associated estrogen
      receptor in oligodendrocytes.
AB  - There is general acceptance that the estrogen receptor can act as a transcription
      factor. However, estrogens can also bind to receptors that are located at the
      plasma membrane and stimulate rapid intracellular signaling processes. We
      recently showed that a membrane-associated estrogen receptor (mER) is present
      within myelin and at the oligodendrocyte (OL) plasma membrane. To understand the
      physiological function of mER in OLs, we investigated its cellular localization
      and involvement in rapid signaling in CG4 cells and OL primary cultures. An
      ERalpha was expressed along the lacy network of veins in the membrane sheets and
      in the perikaryon and nucleus in OLs. ERbeta was located in the nucleus, and to a
      lesser extent along the veins. The expression of ERalpha and ERbeta in OL
      membranes was confirmed by Western analysis of isolated membranes. OL membranes
      mainly had truncated forms of ERalpha, 53 and 50 kDa, in addition to some 65 kDa
      form, whereas ERbeta was a 54 kDa form. CG4 cells and OLs were pulsed with
      17alpha- and 17beta-estradiol for various times and the total lysates were
      analyzed for phosphorylated kinases. Both 17alpha- and 17beta-estradiol elicited
      rapid phosphorylation of p42/44MAPK, Akt, and GSK-3beta within 8 min. This rapid
      signaling is consistent with estradiol ligation of a membrane form of ER. Since
      17alpha-estradiol is produced at higher concentrations than 17beta-estradiol in
      the brain of both sexes, signaling via 17alpha-estradiol-liganded mER may have an
      important function in OLs.

PMID- 18709648
TI  - Mitogen-activated protein kinase-signaling stimulates Muller glia to proliferate
      in acutely damaged chicken retina.
AB  - Muller glia in the mature retina have the capacity to become progenitor-like
      cells in a many different vertebrate classes. The cell-signaling pathways that
      control the ability of mature Muller glia to become progenitor-like cells remain
      uncertain. The purpose of this study was to investigate the roles of the Mitogen
      Activated Protein Kinase (MAPK) pathway in regulating the activity of Muller glia
      in the chicken retina. In response to acute retinal damage, we found that Muller
      glia accumulated phosphorylated ERK1/2 and phospho-CyclicAMP Response Element
      Binding-protein (pCREB), and transiently expressed immediate early genes, cFos
      and Egr1, that are known to be downstream of MAPK-signaling. Egr1 and pCREB were
      normally expressed by retinal progenitors in the circumferential marginal zone
      (CMZ), whereas cFos and pERK1/2 were not. In addition, small molecule inhibitors
      of MEK (UO126) and the FGF-receptor (SU5402) suppressed the proliferation of
      Muller glia-derived progenitor-like cells. These inhibitors suppressed the
      accumulation of Egr1 and pCREB, whereas levels of cFos were unaffected in the
      glial cells. These findings suggest that Egr1 and pCREB are downstream of the
      signaling cascade activated by FGF-receptors and ERK1/2. Further, our findings
      suggest that Egr1 and pCREB may promote glial proliferation. We propose that
      activation of both the FGF-receptor and ERK1/2-pathway is required for the
      proliferation and transdifferentiation of Muller glia into progenitor-like cells.

PMID- 18709649
TI  - Hypoosmotic swelling affects zinc homeostasis in cultured rat astrocytes.
AB  - Astrocyte swelling is observed in different types of brain injury including
      hepatic encephalopathy (HE). This study investigates the role of astrocyte
      swelling on Zn2+ homeostasis in hypoosmotically treated astrocytes by using the
      Zn2+ indicators Newport-Green, Zinquin, and RhodZin-3. Hypoosmolarity (205
      mosmol/L) led to a persistent increase of the intracellular "free" Zn2+
      concentration [Zn2+](i) within 15 min, which was reversible after reinstitution
      of normoosmolarity (305 mosmol/L). The hypoosmotic [Zn2+](i) increase was
      abolished in the presence of the Zn2+ chelator TPEN, the NMDA receptor
      antagonists MK-801 and AP5, the antioxidant epigallocatechin gallate, and the
      nitric oxide synthase inhibitors L-NMMA and TRIM. Hypoosmolarity triggered
      nuclear accumulation of the metal response element-binding transcription factor
      MTF-1 and the specificity protein Sp1 and expression of the mRNAs encoding
      metallothionein and the Sp1-regulated peripheral-type benzodiazepine receptor
      (PBR). These effects were abolished by the Zn2+ chelator TPEN. The data suggest
      that astrocyte swelling affects gene expression by modulation of [Zn2+](i).
      Whereas Zn2+-dependent upregulation of metallothionein may help to counteract
      excessive astrocyte swelling and production of reactive oxygen and nitrogen oxide
      species, stimulation of PBR expression may augment HE development.

PMID- 18709650
TI  - Adiponectin and alcoholic fatty liver disease.
AB  - Worldwide, one of the most prevalent forms of chronic disease is alcoholic fatty
      liver, which may progress to more severe forms of liver injury including
      steatohepatitis, fibrosis, and cirrhosis. The molecular mechanisms by which
      ethanol consumption causes accumulation of hepatic lipid are multiple and
      complex. Chronic ethanol exposure is thought to cause enhanced hepatic
      lipogenesis and impaired fatty acid oxidation by inhibiting key hepatic
      transcriptional regulators such as AMP-activated kinase (AMPK), sirtuin 1
      (SIRT1), PPAR-gamma coactivator alpha (PGC-1alpha), peroxisome proliferator
      activated receptor alpha (PPARalpha), and sterol regulatory element-binding
      protein 1 (SREBP-1). Adiponectin is an adipose-derived hormone with a variety of
      beneficial biological functions. Increasing evidence suggests that altered
      adiponectin production in adipose tissue and impaired expression of hepatic
      adiponectin receptors (AdipoRs) are associated with the development of alcoholic
      liver steatosis in several rodent models. More importantly, studies have
      demonstrated a protective role of adiponectin against alcoholic liver steatosis.
      The hepato-protective effect of adiponectin is largely mediated by the
      coordination of multiple signaling pathways in the liver, leading to enhanced fat
      oxidation, reduced lipid synthesis and prevention of hepatic steatosis. This
      review begins with an assessment of the current understanding of the role of
      adiponectin and its receptors in the regulation of lipid homeostasis in liver,
      with emphasis on their relationship to the development of alcoholic liver
      steatosis. Following sections will review hepatic signaling molecules involved in
      the protective actions of adiponectin against alcoholic fatty liver and summarize
      the current knowledge of regulatory mechanisms of adiponectin expression and
      secretion in response to chronic ethanol exposure. We will conclude with a
      discussion of potential strategies for treating human alcoholic fatty liver
      disease (AFLD), including nutritional and pharmacological modulation of
      adiponectin and its receptors.

PMID- 18709651
TI  - Three-photon microscopy shows that somatic release can be a quantitatively
      significant component of serotonergic neurotransmission in the mammalian brain.
AB  - Recent experiments on monoaminergic neurons have shown that neurotransmission can
      originate from somatic release. However, little is known about the quantity of
      monoamine available to be released through this extrasynaptic pathway or about
      the intracellular dynamics that mediate such release. Using three-photon
      microscopy, we directly imaged serotonin autofluorescence and investigated the
      total serotonin content, release competence, and release kinetics of somatic
      serotonergic vesicles in the dorsal raphe neurons of the rat. We found that the
      somata of primary cultured neurons contain a large number of serotonin-filled
      vesicles arranged in a perinuclear fashion. A similar distribution is also
      observed in fresh tissue slice preparations obtained from the rat dorsal raphe.
      We estimate that the soma of a cultured neuron on an average contains about 9
      fmoles of serotonin in about 450 vesicles (or vesicle clusters) of < or =370 nm
      average diameter. A substantial fraction (>30%) of this serotonin is released
      with a time scale of several minutes by K(+)-induced depolarization or by para
      chloroamphetamine treatment. The amount of releasable serotonin stored in the
      somatic vesicles is comparable to the total serotonin content of all the synaptic
      vesicles in a raphe neuron, indicating that somatic release can potentially play
      a major role in serotonergic neurotransmission in the mammalian brain.

PMID- 18709652
TI  - Validation of a novel biomarker for acute axonal injury in experimental
      autoimmune encephalomyelitis.
AB  - In multiple sclerosis, inflammatory axonal injury is a key pathological mechanism
      responsible for the development of progressive neurological dysfunction. The
      injured axon represents a therapeutic target in this disease; however,
      therapeutic trials of neuroprotective candidates will initially require
      preclinical testing in an animal model of inflammatory axonal injury and
      subsequently the development of a reliable paraclinical measure of axonal
      degeneration in humans. In the present study, we demonstrate the validity of
      serum phosphorylated neurofilament H (pNF-H) as a marker of axonal injury in
      murine experimental autoimmune encephalomyelitis (EAE). At the time of maximum
      disease severity (EAE day 22), the average serum pNF-H level reached 5.7 ng/ml,
      correlating significantly with the EAE paraplegia score (r = 0.75, P < 0.001). On
      average, 40% of axons in the spinal cord were lost in EAE, and serum pNF-H levels
      were highly correlated with axon loss (r = 0.8, P < 0.001). Axonal injury was a
      severe and acute event, insofar as serum pNF-H levels were not significantly
      elevated at early (EAE day 12) or late (EAE days 35 and 50) disease time points.
      Our results demonstrate that acute inflammatory axonal injury is a pathological
      feature of murine MOG(35-55) EAE, indicating that this model may mirror the acute
      pathological events in active multiple sclerosis lesions. Furthermore, we have
      validated the serum pNF-H assay as an unbiased measurement of axonal injury in
      EAE, facilitating rapid screening of potential neuroprotective therapies in this
      model.

PMID- 18709653
TI  - Polyhydroxylated fullerene derivative C(60)(OH)(24) prevents mitochondrial
      dysfunction and oxidative damage in an MPP(+) -induced cellular model of
      Parkinson's disease.
AB  - To find effective agents for Parkinson's disease (PD) prevention and therapy, we
      examined the protective effects of the polyhydroxylated fullerene derivative
      C(60)(OH)(24) in a 1-methyl-4-phenylpyridinium (MPP(+)) -induced acute cellular
      PD model in human neuroblastoma cells and the free radical scavenging effects in
      this model with an electron spin resonance (ESR) spectrometer. Pretreatment with
      C(60)(OH)(24) at concentrations greater than 20 microM showed significant
      protective effects on MPP(+) -induced loss in cell viability, decreases in
      mitochondrial function (including mitochondrial membrane potential and activities
      of complex I and II), and increases in the levels of reactive oxygen species and
      oxidative damage to DNA and proteins. In addition, C(60)(OH)(24) acts as a phase
      2 enzyme inducer to protect cells from MPP(+) -induced decreases in expression of
      nuclear factor-E2-related factor 2, expression and activity of gamma-glutamyl
      cysteine ligase and level of glutathione. The ESR study showed that C(60)(OH)(24)
      is a powerful radical scavenger for superoxide, hydroxyl, and lipid radicals.
      These data suggest that C(60)(OH)(24) is a mitochondrial protective antioxidant
      with direct radical scavenging activity and indirect antioxidant inducing
      activity.

PMID- 18709654
TI  - The p75 receptor is associated with inflammatory thermal hypersensitivity.
AB  - Inflammatory pain, characterized by a decrease in the nociceptive threshold,
      arises through the actions of inflammatory mediators, and one of the key
      molecules is nerve growth factor (NGF). Here we report that the administration of
      neutralizing antibody to the neurotrophin receptor p75 (p75(NTR)) blocks
      hyperalgesia, which develops with complete Freund's adjuvant (CFA)-induced
      inflammation or with an intraplantar injection of NGF. Although CFA injection
      results in the up-regulation of calcitonin gene-related peptide (CGRP) levels in
      the primary sensory neurons, blocking p75(NTR) abolishes this effect. We further
      demonstrate that pro-NGF is the predominant ligand of p75(NTR) in vivo. Plasmin
      treatment, which is intended to decompose pro-NGF, ameliorates CFA-induced
      hyperalgesia. In addition, an intraplantar injection of pro-NGF induces
      hyperalgesia. These data together suggest that pro-NGF, as well as mature NGF,
      binding to p75(NTR) plays an important role in inflammation-induced hyperalgesia.
      Interference in the binding may provide a therapeutic approach for the treatment
      of inflammatory pain.

PMID- 18709655
TI  - Heterogeneous effects of distinct tocopherol analogues on NO release, cell
      volume, and cell death in microglial cells.
AB  - Tocopherols (vitamin E) are potent antioxidants as well as modulators of enzymes
      involved in signal transduction, like nitric oxide synthase (NOS). In primary
      murine microglial cells and in the microglial cell line BV-2, alpha-, gamma-, and
      delta-tocopherol and alpha-tocopherol acid succinate, respectively, promote
      nitric oxide (NO) release. The NOS inhibitors aminoguanidine and N(G)-methyl-L
      arginine (L-NMMA) suppressed alpha- and gamma-tocopherol-induced NO release, but
      had no significant effect on delta-tocopherol- and alpha-tocopherol acid
      succinate-induced NO release. In BV-2 cells, but not in primary microglial cells,
      gamma- and delta-tocopherol and alpha-tocopherol acid succinate, respectively,
      led to cell death, characterized by exposition of phosphatidylserine on the cell
      surface, chromatin condensation, changes in cell volume, and formation of blebs
      on the cell surface. Aminoguanidine, L-NMMA, and the NO scavenger 2-phenyl
      4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) enhanced apoptosis in gamma
      tocopherol-exposed cells and suppressed apoptosis in delta-tocopherol-treated
      cells, but had no effect on cells supplemented with alpha-tocopherol acid
      succinate. The NO donors sodium nitroprusside and 2-(N,N-diethylamino)
      diazenolate 2-oxide enhanced apoptosis in gamma- or delta-tocopherol-treated
      cells, but rescued cells from alpha-tocopherol acid succinate-induced cell death.

PMID- 18709656
TI  - Retinal pigment epithelial cells promote spatial reorganization and
      differentiation of retina photoreceptors.
AB  - Retina differentiation involves the acquisition of a precise layered arrangement,
      with RPE cells in the first layer in intimate contact with photoreceptors in the
      second layer. Here, we developed an in vitro coculture model, to test the
      hypothesis that RPE cells play a pivotal role in organizing the spatial structure
      of the retina. We cocultured rat retinal neurons with ARPE-19 epithelial cells
      under various experimental conditions. Strikingly, when seeded over RPE cells,
      photoreceptors attached to their apical surfaces and proceeded with their
      development, including the increased synthesis of rhodopsin. Conversely, when we
      seeded RPE cells over neurons, the RPE cells rapidly detached photoreceptors from
      their substrata and positioned themselves underneath, thus restoring the normal
      in vivo arrangement. Treatment with the metalloproteinase inhibitor TIMP-1
      blocked this reorganization, suggesting the involvement of metalloproteinases in
      this process. Reorganization was highly selective for photoreceptors because 98%
      of photoreceptors but very few amacrine neurons were found to redistribute on top
      of RPE cells. Interestingly, RPE cells were much more efficient than other
      epithelial or nonepithelial cells in promoting this reorganization. RPE cells
      also promoted the growth of photoreceptor axons away from them. An additional
      factor that contributed to the distal arrangement of photoreceptor axons was the
      migration of photoreceptor cell bodies along their own neurites toward the RPE
      cells. Our results demonstrate that RPE and photoreceptor cells interact in vitro
      in very specific ways. They also show that in vitro studies may provide important
      insights into the process of pattern formation in the retina.

PMID- 18709657
TI  - Differential effects of the mitochondrial uncoupling agent, 2,4-dinitrophenol, or
      the nitroxide antioxidant, Tempol, on synaptic or nonsynaptic mitochondria after
      spinal cord injury.
AB  - We recently documented the progressive nature of mitochondrial dysfunction over
      24 hr after contusion spinal cord injury (SCI), but the underlying mechanism has
      not been elucidated. We investigated the effects of targeting two distinct
      possible mechanisms of mitochondrial dysfunction by using the mitochondrial
      uncoupler 2,4-dinitrophenol (2,4-DNP) or the nitroxide antioxidant Tempol after
      contusion SCI in rats. A novel aspect of this study was that all assessments were
      made in both synaptosomal (neuronal)- and nonsynaptosomal (glial and neuronal
      soma)-derived mitochondria 24 hr after injury. Mitochondrial uncouplers target
      Ca(2+) cycling and subsequent reactive oxygen species production in mitochondria
      after injury. When 2,4-DNP was injected 15 and 30 min after injury, mitochondrial
      function was preserved in both populations compared with vehicle-treated rats,
      whereas 1 hr postinjury treatment was ineffective. Conversely, targeting
      peroxynitrite with Tempol failed to maintain normal bioenergetics in synaptic
      mitochondria, but was effective in nonsynaptic mitochondria when administered 15
      min after injury. When administered at 15 and 30 min after injury, increased
      hydroxynonenal, 3-NT, and protein carbonyl levels were significantly reduced by
      2,4-DNP, whereas Tempol only reduced 3-NT and protein carbonyls after SCI.
      Despite such antioxidant effects, only 2,4-DNP was effective in preventing
      mitochondrial dysfunction, indicating that mitochondrial Ca(2+) overload may be
      the key mechanism involved in acute mitochondrial damage after SCI. Collectively,
      our observations demonstrate the significant role that mitochondrial dysfunction
      plays in SCI neuropathology. Moreover, they indicate that combinatorial
      therapeutic approaches targeting different populations of mitochondria holds
      great potential in fostering neuroprotection after acute SCI.

PMID- 18709658
TI  - Neuroprotective effects of acetyl-L-carnitine on neuropathic pain and apoptosis:
      a role for the nicotinic receptor.
AB  - Several pathologies related to nervous tissue alterations are characterized by a
      chronic pain syndrome defined by persistent or paroxysmal pain independent or
      dependent on a stimulus. Pathophysiological mechanisms related to neuropathic
      disease are associated with mitochondrial dysfunctions that lead to an activation
      of the apoptotic cascade. In a model of peripheral neuropathy obtained by the
      loose ligation of the rat sciatic nerve, acetyl-L-Carnitine (ALCAR; 100 mg/kg
      intraperitoneally [i.p.] twice daily for 14 days) was able to reduce hyperalgesia
      and apoptosis. In the present study, different mechanisms for the analgesic and
      the antineuropathic effect of ALCAR are described. The muscarinic blocker
      atropine (5 mg/kg i.p.) injected simultaneously with ALCAR did not antagonize the
      ALCAR antihyperalgesic effect on the paw-pressure test but significantly reduced
      the analgesic effect of ALCAR. Conversely, the antineuropathic effect of ALCAR
      was prevented by cotreatment with the nicotinic antagonist mecamylamine (2 mg/kg
      i.p. twice daily for 14 days). A pharmacological silencing of the nicotinic
      receptors significantly reduced the X-linked inhibitor of apoptosis protein
      related protective effect of ALCAR on the apoptosis induced by ligation of the
      sciatic nerve. Taken together, these data highlight the relevance of nicotinic
      modulation in neuropathy treatment.

PMID- 18709659
TI  - Diversity and fluctuation of spine morphology in CA1 pyramidal neurons after
      transient global ischemia.
AB  - Dendritic spines form postsynaptic components of excitatory synapses in CA1
      pyramidal neurons and play a key role in excitatory signal transmission.
      Transient global ischemia is thought to induce excitotoxicity that triggers
      delayed neuronal death in the CA1 region. However, the mechanism underlying
      structural changes of excitatory synapses after ischemia is not completely
      understood. Here, we demonstrate how dendritic spines change in their density and
      structure at an acute stage after transient global ischemia. Intracellular
      staining in vivo showed that the total spine density in basal, proximal, and
      distal apical dendrites increased at 12 hr and 24 hr after ischemia, but returned
      to control levels at 48 hr after ischemia. Consistent increase of spine density
      mainly appeared in non-late depolarizing postsynaptic potential neurons, although
      late depolarizing postsynaptic potential neurons also showed slight increases in
      spine density in these dendrites at the same intervals after ischemia. Golgi
      staining showed increased spine density occurred in less swollen dendrites but
      decreased spine density appeared in severely swollen dendrites at 12 and 24 hr
      after ischemia. In addition, the density and percentage of stubby spines reduced
      at 12 hr and 48 hr, whereas the density of thin spines increased at 12 hr after
      ischemia. The density and percentage of filopodia increased nearly fivefold at 24
      hr after ischemia. Moreover, the density of mushroom spines doubled and its
      percentage increased by 150% at 48 hr after ischemia. These morphological changes
      of spines may be related to neuronal injury in CA1 pyramidal neurons after
      ischemia.

PMID- 18709660
TI  - Pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage:
      putative mechanisms and novel approaches.
AB  - Cerebral vasospasm is a potentially incapacitating or lethal complication in
      patients with aneurysmal subarachnoid hemorrhage (SAH). The development of
      effective preventative and therapeutic interventions has been largely hindered by
      the fact that the underlying pathogenic mechanisms of cerebral vasospasm remain
      poorly understood. However, intensive research during the last 3 decades has
      identified certain mechanisms that possibly play a role in its development.
      Experimental data suggest that calcium-dependent and -independent
      vasoconstriction is taking place during vasospasm. It appears that the breakdown
      products of blood in the subarachnoid space are involved, through direct and/or
      indirect pathways, in the development of vasospasm after SAH. Free radicals
      reactions, an imbalance between vasoconstrictor and vasodilator substances
      (endothelium derived substances, e.g., nitric oxide, endothelin; arachidonic acid
      metabolites, e.g., prostaglandins, prostacyclin), inflammatory processes, an
      upheaval of neuronal mechanisms that regulate vascular tone, endothelial
      proliferation, and apoptosis have all been put forward as causative and/or
      pathogenic factors. Translational research in the field of vasospasm has
      traditionally aimed to identify agents/interventions in order to block the
      cascades initiated after SAH. The combination of novel approaches such as
      cerebral microdialysis, magnetic resonance spectroscopy, proteomics, and
      lipidomics could serve a dual purpose: elucidating the complex pathobiochemistry
      of vasospasm and providing clinicians with tools for early detection of this
      feared complication. The purpose of this Mini-Review is to provide an overview of
      the pathogenesis of cerebral vasospasm and of novel approaches used in basic and
      translational research.

PMID- 18709661
TI  - Astrocytes are very sensitive to develop innate immune responses to lipid-carried
      short interfering RNA.
AB  - Short interfering RNA (siRNA) inhibits the synthesis of specific proteins through
      RNA interference (RNAi). However, siRNA can induce innate immune responses that
      are mediated by toll-like receptors (TLRs) in cells of the immune system. Here,
      we sought to evaluate whether siRNA can induce such responses in glial cells. We
      examined the effects of various siRNA sequences prepared with lipids
      (oligofectamine). Lipid-siRNA induced variable degrees of silencing-independent
      nonspecific effects, e.g. increased Stat1 and Cox-2 expression and release of IL
      6 and IP-10 in primary astroglia. This was prevented through chemical
      modification of siRNA by nucleoside 2'-O-methylation, without impairing specific
      gene silencing. Lipid-siRNA also induced nonspecific responses in purified
      astroglia, but not in microglia, or 3T3 cells. The highest TLR7 and TLR3 mRNA
      expression was found in microglia and purified astroglia, respectively.
      Accordingly, the TLR3 agonist poly(I:C) (PIC) induced higher release of IFN-beta
      in primary and purified astroglia than in microglia. As siRNA, PIC induced IP-10,
      Stat1, VCAM-1, and Cox-2 and increased TLR3 mRNA expression. The effects of lipid
      siRNA in purified astrocytes were attenuated after silencing TLR3 or TLR7
      expression, and by the PKR inhibitor 2-aminopurine. Furthermore, lipid-siRNA
      induced the expression of RIG-I. In contrast, siRNA devoid of lipids did not
      enter the astrocytes, did not silence gene expression, and did not induce Stat1
      or Cox-2. The results show that, in astroglia, lipid-siRNA induces innate immune
      responses that are mediated, at least in part, by intracellular mechanism
      dependent on TLR7, TLR3, and helicases.

PMID- 18709662
TI  - Muscarinic-2 and orexin-2 receptors on GABAergic and other neurons in the rat
      mesopontine tegmentum and their potential role in sleep-wake state control.
AB  - Acetylcholine (ACh) plays an important role in the promotion of paradoxical sleep
      (PS) with muscle atonia through the muscarinic-2 receptor (M2R) in the
      mesopontine tegmentum. Conversely, orexin (Orx or hypocretin) appears to be
      critical for the maintenance of waking with muscle tone through the orexin-2 (or
      hypocretin-B) receptor (Orx2R), which is lacking in dogs having narcolepsy with
      cataplexy. In dual-immunostained material viewed under fluorescence microscopy,
      we examined the presence and distribution of M2R or Orx2R labeling on all
      neuronal nuclei (NeuN)-stained neurons or on glutamic acid decarboxylase (GAD)
      stained neurons through the mesopontine tegmentum. Applying stereological
      analysis, we determined that many neurons bear M2Rs on their membrane (
      approximately 6,300), including relatively large, non-GABAergic cells, which
      predominate (>75%) in the oral and caudal pontine (PnO and PnC) reticular fields,
      and small, GABAergic cells ( approximately 2,800), which predominate (>80%) in
      the mesencephalic (Mes) reticular formation. Many neurons bear Orx2Rs on their
      membrane ( approximately 6,800), including relatively large, non-GABAergic cells,
      which predominate (>70%) through all reticular fields, and comparatively few
      GABAergic cells ( approximately 700). In triple-immunostained material viewed by
      confocal microscopy, many large neurons in PnO and PnC appear to bear both M2Rs
      and Orx2Rs on their membrane, indicating that ACh and Orx could exert opposing
      influences of inhibition vs. excitation on putative reticulo-spinal neurons and
      thus attenuate vs. facilitate activity and muscle tone. A few GABAergic cells
      bear both receptors and could as PS inhibitor neurons serve under these different
      influences to control PS effector neurons and accordingly gate PS and muscle
      atonia appropriately across sleep-wake states.

PMID- 18709664
TI  - Multiple recurrent chromosomal breakpoints in mantle cell lymphoma revealed by a
      combination of molecular cytogenetic techniques.
AB  - Mantle cell lymphoma (MCL) is genetically characterized by 11q13 translocations
      leading to the overexpression of CCND1, and additional secondary genomic
      alterations that may be important in the progression of this disease. We have
      analyzed 22 MCL cases and 10 MCL cell lines using multicolor fluorescence in situ
      hybridization (M-FISH), FISH, and comparative genomic hybridization (CGH). The 19
      cases with abnormal karyotype showed the t(11;14)(q13;q32) translocation and,
      additionally, 89% of cases showed both numerical (n = 58) and structural (n = 77)
      aberrations. All but one MCL cell line showed t(11;14) and structural and
      numerical alterations in highly complex karyotypes. Besides 11 and 14, the most
      commonly rearranged chromosomes were 1, 8, and 10 in the tumors and 1, 8, and 9
      in the cell lines. No recurrent translocations other than the t(11;14) were
      identified. However, we identified 17 recurrent breakpoints, the most frequent
      being 1p22 and 8p11, each observed in four cases and two cell lines.
      Interestingly, five tumors and four cell lines displayed a complex t(11;14),
      cryptic in one case and two cell lines, preferentially involving chromosome 8. In
      typical MCL, ATM gene deletions were significantly associated with a high number
      of structural and numerical alterations. In conclusion, MCL does not have
      recurrent translocations other than t(11;14), but shows recurrent chromosomal
      breakpoints. Furthermore, most MCL harbor complex karyotypes with a high number
      of both structural and numerical alterations affecting several common
      breakpoints, leading to various balanced and unbalanced translocations.

PMID- 18709663
TI  - Expression and mutational analysis of MET in human solid cancers.
AB  - MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF)
      regulate a variety of cellular functions, many of which can be dysregulated in
      human cancers. Activated MET signaling can lead to cell motility and scattering,
      angiogenesis, proliferation, branching morphogenesis, invasion, and eventual
      metastasis. We performed systematic analysis of the expression of the MET
      receptor and its ligand HGF in tumor tissue microarrays (TMA) from human solid
      cancers. Standard immunohistochemistry (IHC) and a computerized automated scoring
      system were used. DNA sequencing for MET mutations in both nonkinase and kinase
      domains was also performed. MET was differentially overexpressed in human solid
      cancers. The ligand HGF was widely expressed in both tumors, primarily
      intratumoral, and nonmalignant tissues. The MET/HGF likely is functional and may
      be activated in autocrine fashion in vivo. MET and stem cell factor (SCF) were
      found to be positively stained in the bronchioalevolar junctions of lung tumors.
      A number of novel mutations of MET were identified, particularly in the
      extracellular semaphorin domain and the juxtamembrane domain. MET-HGF pathway can
      be assayed in TMAs and is often overexpressed in a wide variety of human solid
      cancers. MET can be activated through overexpression, mutation, or autocrine
      signaling in malignant cells. Mutations in the nonkinase regions of MET might
      play an important role in tumorigenesis and tumor progression. MET would be an
      important therapeutic antitumor target to be inhibited, and in lung cancer, MET
      may represent a cancer early progenitor cell marker.

PMID- 18709665
TI  - The first cinematic presentation of a possible rhythmic movement disorder in a
      Disney film precedes its scientific debut by 60 years.

PMID- 18709667
TI  - Mitochondrial DNA single deletion in a patient with postural tremor.

PMID- 18709668
TI  - High frequency extradural motor cortex stimulation transiently improves axial
      symptoms in a patient with Parkinson's disease.
AB  - In a primate model of Parkinson's disease (PD), the benefit of extradural motor
      cortex stimulation (EMCS) was associated with high-frequency stimulation (130
      Hz), whereas no significant motor improvement was achieved at 10 Hz or
      intermediate frequencies of stimulation. We report the case of a 72-year-old
      female patient affected by severe PD who underwent bilateral EMCS. In baseline
      med-off condition the patient was unable to arise from a chair and to stand
      without assistance. Stimulation at 3 and 60 Hz failed to provide any improvement
      of symptoms, whereas, when stimulating at 130 Hz, axial akinesia and walking
      improved consistently: the patient, in med-off condition, was able to arise from
      chair and to walk without assistance. The patient underwent two brain 99mTc-
      Ethylcysteinate Dimer-SPECT studies: semiquantitative and Statistical Parametric
      Mapping revealed that the regional cerebral perfusion was significantly increased
      in the supplementary motor area during stimulation at 130 Hz. After five months,
      the benefit of EMCS gradually disappeared.

PMID- 18709666
TI  - The ventral nucleus of the lateral lemniscus of the gerbil (Meriones
      unguiculatus): organization of connections with the cochlear nucleus and the
      inferior colliculus.
AB  - The spatial organization of projections from the ventral cochlear nucleus (VCN)
      to the ventral nucleus of the lateral lemniscus (VNLL) and from the VNLL to the
      central nucleus of the inferior colliculus (CNIC) was investigated by using
      neuroanatomical tracing methods in the gerbil. In order to label cells in the
      VNLL that project to the CNIC, focal injections of biotinylated dextran amine
      (BDA) were made into different CNIC regions. Retrogradely labeled cells were
      distributed throughout the dorsal-to-ventral axis of the VNLL in all cases. In
      contrast, the distribution of labeled cells across the lateral-to-medial
      dimension of the VNLL was related to the location of the injection site along the
      dorsolateral to ventromedial (frequency) axis of the CNIC. Cells projecting to
      dorsolateral (low-frequency) regions of the CNIC were located peripherally in the
      VNLL, mainly laterally and caudally, whereas those projecting to ventromedial
      (high-frequency) regions of the CNIC tended to be clustered centrally.
      Projections to the VNLL were labeled anterogradely following injections of BDA in
      the VCN. The distribution of terminal fields in the VNLL closely paralleled the
      topographic arrangement of cells projecting to the CNIC; projections from
      ventrolateral (low-frequency) areas of the VCN terminated mainly along the
      lateral and caudal borders of the VNLL, whereas projections from dorsomedial
      (high-frequency) areas terminated in more central regions. The results
      demonstrate a topographic organization of the major afferent and efferent
      connections of the gerbil VNLL.

PMID- 18709669
TI  - Case control MR-CISS and 3D TOF MRA imaging study of medullary compression and
      hypertension in hemifacial spasm.
AB  - The association between ventro-lateral medulla (VLM) compression and hypertension
      has not been compared between hemifacial spasm (HFS) and healthy controls using
      advanced magnetic resonance imaging (MRI) techniques specific for detecting
      neurovascular compression. We conducted a MR-constructive interference in a
      steady state (CISS) and Magnetic Resonance Angiography (MRA) imaging study of VLM
      compression in hypertensive HFS patients and hypertensive controls compared with
      healthy controls without hypertension. A total of 125 subjects, including 45 HFS,
      51 healthy controls, and 29 hypertensive controls were included. When compared
      with healthy controls, there was a higher prevalence of VLM compression in
      hypertensive HFS (82.2% vs. 41.2%, P < 0.001, odds ratio = 6.61, 95% CI 2.37
      19.48), and hypertensive controls (72.4% vs. 41.2%, P = 0.007, odds ratio = 3.75,
      95% CI 1.42-9.89). Although the prevalence in hypertensive HFS was higher
      compared to controls with hypertension, this was not significant (82.2% vs.
      72.4%). Compared to healthy controls, there was an increasing proportion of
      higher compression scores on the right (P = 0.001) and left (P = 0.038) (chi
      square for trend) in hypertensive HFS and hypertensive controls. Kruskal-Wallis
      test revealed that the mean right compression score on the right (P = 0.003),
      left (P = 0.026) and the mean bilateral compression score (P < 0.0001) was higher
      in hypertensive HFS and hypertensive controls compared to healthy controls. MR
      CISS and MRA imaging revealed a greater likelihood of VLM compression in
      hypertensive HFS and hypertensive controls compared to healthy controls. Our case
      control study provides further support that VLM compression is associated with
      hypertension in HFS.

PMID- 18709670
TI  - Orolingual tremor as unusual presentation of anti-Hu paraneoplastic syndrome.

PMID- 18709671
TI  - Visual object recognition and attention in Parkinson's disease patients with
      visual hallucinations.
AB  - Visual hallucinations (VH) are common in Parkinson's disease (PD) and are
      hypothesized to be due to impaired visual perception and attention deficits. We
      investigated whether PD patients with VH showed attention deficits, a more
      specific impairment of higher order visual perception, or both. Forty-two
      volunteers participated in this study, including 14 PD patients with VH, 14 PD
      patients without VH and 14 healthy controls (HC), matched for age, gender,
      education level and for level of executive function. We created movies with
      images of animals, people, and objects dynamically appearing out of random noise.
      Time until recognition of the image was recorded. Sustained attention was tested
      using the Test of Attentional Performance. PD patients with VH recognized all
      images but were significantly slower in image recognition than both PD patients
      without VH and HC. PD patients with VH showed decreased sustained attention
      compared to PD patients without VH who again performed worse than HC. In
      conclusion, the recognition of objects is intact in PD patients with VH; however,
      these patients where significantly slower in image recognition than patients
      without VH and HC, which was not explained by executive dysfunction. Both image
      recognition speed and sustained attention decline in PD, in a more progressive
      way if VH start to occur.

PMID- 18709672
TI  - SCOPA-sleep and PDSS: two scales for assessment of sleep disorder in Parkinson's
      disease.
AB  - This study evaluated the comparative validity and usefulness of the Parkinson's
      Disease Sleep Scale (PDSS) and the Scales for Outcomes in PD-Sleep Scale (SCOPA
      S), two disease-specific rating scales for assessing sleep disorders in
      Parkinson's disease (PD). Hoehn and Yahr staging (HY), SCOPA-Motor, Mini-Mental
      State Examination, Clinical Impression of Severity Index for PD, Hospital Anxiety
      and Depression Scale, EuroQoL, and SCOPA-Psychosocial, in addition to PDSS and
      SCOPA-S (night-time sleep (NS) and daytime sleepiness (DS) subscales), were
      applied to 187 consecutive PD patients. PDSS and SCOPA-S proved similar in
      acceptability, scaling assumptions, precision, and internal consistency
      (Cronbach's alpha = 0.82-0.84). Factor analysis revealed five separate factors
      for PDSS (67% of the variance) and one factor for each SCOPA-S subscale (60% of
      the variance for NS and 57% for DS). Correlation coefficient between PDSS and
      SCOPA-S NS was -0.60. Sleep scales correlated moderately with mood, low-to
      moderate with HRQoL, and low with the rest of measures. PDSS and SCOPA-S DS
      discriminated between patients grouped by HY severity levels and disease
      duration. Cutoff points of 82/83 for PDSS and 6/7 for SCOPA-S NS were drawn to
      identify PD patients with sleep problems. Depression/anxiety scores explained 26%
      for PDSS and 22% for SCOPA-S NS scores. Both scales provide valid, reliable, and
      useful means to evaluate sleep disorders in PD. PDSS may be used to obtain a
      profile about potential causes of "bad sleep," but is barely useful to assess DS,
      whereas SCOPA-S assesses nocturnal sleep disorders and daytime somnolence at a
      similar extent, without exploring the potential causes.

PMID- 18709674
TI  - A patient with a parkinsonian syndrome illustrating the difficult differential
      diagnosis between multisystem atrophy and Parkinson's disease.

PMID- 18709675
TI  - Do dyskinesia and pain share common pathophysiological mechanisms in Parkinson's
      disease?
AB  - Plastic changes within the striatum resulting from pulsatile dopaminergic
      stimulation are thought to lead to dyskinesia in patients with Parkinson's
      disease (PD). The basal ganglia play a role in processing pain. We hypothesized
      that the plastic changes that lead to dyskinesia may also mediate pain responses.
      Our objective was to compare the change in pain sensitivity after levodopa
      administration between stable responders, fluctuators without dyskinesia, and
      dyskinetic patients, and to compare pain sensitivity between PD and healthy
      subjects. Fifty patients with PD were assessed with cold water immersion after
      overnight withdrawal of dopaminergic medications and again after a standard
      levodopa challenge, and carefully classified into stable responder (n = 12),
      fluctuator (n = 15), and dyskinetic (n = 23) groups. Twenty age-matched controls
      were also tested. PD patients "off"-medication had a lower threshold (P = 0.016)
      and tolerance (P < 0.0001) to cold pain compared to controls. After levodopa
      administration, dyskinetic patients experienced a large increase in cold pain
      threshold (48%) and tolerance (66%) that was absent in stable responders (P =
      0.038 and P = 0.015); there was no significant difference in pain sensitivity
      change scores between the fluctuator and either the stable responder or
      dyskinetic groups. Our results suggest that dyskinesia and pain may share common
      pathophysiological mechanisms in PD.

PMID- 18709676
TI  - Praxis-induced seizures misdiagnosed as cataplexy: a case report.

PMID- 18709677
TI  - Psychogenic movement disorders in children.
AB  - Psychogenic movement disorders (PMDs) are well characterized in adults, but
      childhood-onset PMDs have not been extensively studied. We reviewed the medical
      records of children who were diagnosed in our clinic with PMDs since 1988 and
      identified 54 patients with PMDs, representing 3.1% of our pediatric movement
      disorder population and 5.7% of all PMD cases. The mean age at symptom onset was
      14.2 years (+/-2.11, range 7.6-17.7). Similar to published data in adults, two
      thirds of children exhibited multiple PMD phenotypes, the most common being
      tremor followed by dystonia and myoclonus. Most PMDs were abrupt in onset,
      paroxysmal and triggered by identifiable physical or psychological trauma. As in
      adults, childhood PMDs were more likely to affect females, but there was no
      female predominance in children less than 13 years old. Although prior studies
      suggest that medically unexplained symptoms beginning in childhood often follow a
      benign course, this cohort of children experienced marked disability and
      morbidity related to PMDs, including prolonged school absences and unnecessary
      surgical procedures in more than one-fifth of patients.

PMID- 18709678
TI  - Intact presupplementary motor area function in early, untreated Parkinson's
      disease.
AB  - Although motor symptoms of Parkinson's disease (PD) are initially responsive to
      dopamine replacement therapy, nonresponsive features develop over time,
      suggesting that impaired dopaminergic function alone may not be wholly
      responsible for all the motor features of the disease. Previous studies suggest
      impaired function in the presupplementary motor area (pre-SMA) in PD. Our
      objective was to determine whether pre-SMA abnormalities are present in untreated
      patients with early disease. We measured N-acetyl aspartate (NAA)/creatine (Cr)
      and choline (Cho)/Cr ratios in pre-SMA in 26 untreated patients with early PD
      (disease duration 3.0 +/- 2.0 yr) and 15 control subjects with single voxel
      magnetic resonance spectroscopy. Neither NAA/Cr nor Cho/Cr ratios differed
      significantly between groups. These observations suggest that, although pre-SMA
      function is impaired in moderately advanced PD, it is relatively spared in early
      disease. We suggest that pre-SMA dysfunction is in part responsible for the
      dopamine nonresponsive features associated with disease progression.

PMID- 18709679
TI  - Primary progressive myoclonus of aging.
AB  - Myoclonus in older individuals usually occurs in the context of associated
      neurologic features which allow the diagnosis of the underlying disorder. We
      encountered 7 patients with a newly recognized myoclonus syndrome; we use the
      term primary progressive myoclonus of aging (PPMA) for this syndrome. Our purpose
      was to characterize the clinical and electrophysiological properties of this
      syndrome. Our database was searched for the presence of "myoclonus" in the
      physical examination. Medical records and laboratory data were retrospectively
      reviewed, including electrophysiology data. We applied our criteria for PPMA: (1)
      asymmetric symptomatic action myoclonus, (2) >/=65 years of age, (3) cortical
      myoclonus physiology, (4) no dementia, (5) no associated features of defined
      neurodegenerative disorders, and (6) no secondary cause found. Seven patients
      fulfilled criteria. Age at presentation ranged from 70 to 87 years. Mean duration
      from myoclonus onset to last follow-up was 2.9 years. Electrophysiology showed
      positive-negative back-averaged transients, consistent with cortical myoclonus.
      No patient demonstrated dementia. Brain imaging in all cases was unremarkable.
      PPMA is a unique syndrome with characteristic findings that differentiate it from
      dementias and defined neurodegenerative syndromes. It is important to distinguish
      primary PPMA from other syndromes seen in older individuals to avoid diagnostic
      confusion. Some cases showed a response to levetiracetam.

PMID- 18709680
TI  - Cancer and blood concentrations of the comutagen harmane in essential tremor.
AB  - Blood concentrations of harmane, a tremor-producing neurotoxin, are elevated in
      essential tremor (ET). Harmane is also a comutagen. Using a case-control design,
      we compared the prevalence of cancer in ET cases vs. controls, and determined
      whether blood harmane concentrations are elevated among ET cases with cancer.
      66/267 (24.7%) ET cases vs. 55/331 (16.6%) controls had cancer (adjusted OR 1.52,
      95% CI 1.01-2.30, P = 0.04). Among specific cancer types, colon cancer was more
      prevalent in ET cases than controls (2.6% vs. 0.6%, P = 0.04). Log blood harmane
      concentration was higher in ET cases vs. controls (P = 0.02) and in participants
      with vs. without cancer (P = 0.02). Log blood harmane concentration was highest
      in ET cases with cancer when compared with other groups (P = 0.009). These links
      between cancer and ET and between high blood harmane and cancer in ET deserve
      further study.

PMID- 18709681
TI  - A comparative study of physical performance measures in Parkinson's disease.
AB  - The objective of this study is to compare physical performance measures for their
      ability to discriminate between levels of disability and disease severity in
      Parkinson's disease (PD). Disability in PD is commonly assessed by patient self
      report, which may be limited by patient insight. METHODS: Seventy-nine patients
      with PD were tested with seven performance measures: Physical Performance Test
      (PPT), modified Physical Performance Test (mPPT), Short Physical Performance
      Battery (SPPB), Performance Test of Activities of Daily Living (PADL), Berg
      Balance Scale (BBS), Timed Up and Go (TUG), and Functional Reach (FR). These
      measures were compared with patient-reported disability on the Older Americans
      Resource and Services Disability subscale (OARS) and disease severity on the
      Unified Parkinson's Disease Rating Scale (UPDRS). The performance measures were
      more sensitive to levels of disease severity than disability. Four measures
      discriminated across quartiles of disability (PPT, mPPT, BBS, TUG: P < 0.05),
      whereas all seven measures discriminated across quartiles of the Total UPDRS
      (PPT, mPPT, BBS, TUG, FR: P < 0.01; SPPB, PADL: P < 0.05). However, no measure
      consistently discriminated between subgroups with a range of early and advanced
      disease severity. The seven physical performance measures showed different
      profiles of strengths and weaknesses in assessing disability and disease
      severity. The results of this study will facilitate choosing performance measures
      for clinical care and clinical trials in PD.

PMID- 18709682
TI  - Prevalence and correlates of neuropsychiatric symptoms in Parkinson's disease
      without dementia.
AB  - A cross-sectional study of the profile of psychiatric symptoms and their
      relationships to medications, executive performance, and excessive daytime
      somnolence (EDS) was conducted on 1351 consecutive Parkinson's disease patients
      without dementia (PD-ND). Ratings were: neuropsychiatric inventory (NPI);
      hospital anxiety and depression scale (HADS); executive performance (semantic,
      phonemic, and alternating verbal fluencies); and the Epworth sleepiness scale
      (ESS). Eighty-seven percent of the subjects reported at least one psychiatric
      symptom. The most common were depression (70%), anxiety (69%), apathy (48%), and
      irritability (47%). Fifty percent of the patients had HADS-depression scores
      ranging from possible (8-10; 22%) to probable (>or=11; 28%) depression. Executive
      impairment was found in 41% and EDS in 26% of subjects. All considered variables
      were significantly more common with longer duration and more severe disease. Only
      depression appeared to be influenced by type of medication, being less prevalent
      among patients treated with DAs. Five NPI clusters were identified among patients
      scoring >or=1 on the NPI (87.3%): patients exhibiting predominantly apathy
      (12.7%), psychosis (3%), depression (13%), anxiety (15.6%), and "low-total NPI"
      (43.2%). Neuropsychiatric symptoms are common in nondemented PD patients
      suggesting that they are an integral part of PD from the beginning of the disease
      and appears more related to disease progression than to the type of
      antiparkinsonian medication. Apathy emerged as an independent construct in PD-ND,
      indicating the need to address specific therapeutical approaches targeted toward
      this particular symptom.

PMID- 18709683
TI  - Apathy and anhedonia rating scales in Parkinson's disease: critique and
      recommendations.
AB  - Apathy is a common condition in Parkinson's disease (PD) and is generally defined
      as a lack of motivation. It is associated with more severe cognitive dysfunction
      and a decrease in activities of daily living (ADL) performance. Anhedonia, the
      inability to experience pleasure, can be a symptom of both depressive and
      apathetic syndromes. The Movement Disorder Society (MDS) commissioned a task
      force to assess the clinimetric properties of apathy and anhedonia scales in PD
      patients. A systematic literature review was conducted to identify scales that
      have either been validated or used in PD patients. Apathy scales identified for
      review include the Apathy Evaluation Scale (AES), the Apathy Scale (AS), the
      Apathy Inventory (AI), and the Lille Apathy Rating Scale (LARS). In addition,
      item 4 (motivation/initiative) of the Unified Parkinson's Disease Rating Scale
      (UPDRS) and item 7 (apathy) of the Neuropsychiatric Inventory (NPI) were
      included. Anhedonia scales identified for review were the Snaith-Hamilton
      Pleasure Scale (SHAPS) and the Chapman scales for physical and social anhedonia.
      Only the AS is classified as "recommended" to assess apathy in PD. Although item
      4 of the UPDRS also meets the criteria to be classified as recommended, it should
      be considered for screening only because of the obvious limitations of a single
      item construct. For the assessment of anhedonia, only the SHAPS meets the
      criteria of "Suggested." Information on the validity of apathy and anhedonia
      scales is limited because of the lack of consensus on diagnostic criteria for
      these conditions.

PMID- 18709684
TI  - Burden, perceived health status, and mood among caregivers of Parkinson's disease
      patients.
AB  - The objective of this study is to describe the characteristics of the caregivers
      of patients with Parkinson's disease (PD) and to analyze the association between
      these characteristics and caregiver burden, perceived health and mood status, and
      identify their predictors. A multicenter, nationwide, observational, cross
      sectional study that included 289 patient-caregiver pairs was conducted.
      Caregiver self-assessments were the Hospital Anxiety and Depression Scale (HADS),
      EuroQol (EQ), and Zarit Caregiver Burden Inventory (ZCBI). Most caregivers in the
      study were women aged 60 years or thereabouts. Over two thirds were gainfully
      employed or housewives, 75% were patients' spouses, and the majority (96.5%) had
      been permanently taking care of the patient for 6 +/- 5.4 years. Less than 5% of
      patients were in the most advanced stages of disease, and direct costs were 6,350
      euros per patient per year. Caregivers had more mood disorders and worse health
      related quality of life (HRQol; EQ-Tariff) than did the general population.
      Caregiver HADS and EuroQol scores displayed a weak correlation (r(S) = 0.01-0.28)
      with patient-related variables (disease duration, HY, SCOPA-Motor, SCOPA-AUT,
      HADS, PPRS, and CISI-PD) whereas the ZCBI correlated moderately (r(S) = 0.27
      0.47). Among caregivers, the EQ-Tariff was significantly lower and the HADS
      Anxiety scores significantly higher for women. ZCBI and HADS-depression, though
      not EuroQol and HADS-anxiety, scores significantly increased with increasing PD
      severity levels. Caregivers' affective status proved the most important factor
      influencing their burden and perceived health, whereas patient-related variables
      influenced caregiver burden and mood but not health status. In PD, prevalence of
      affective disorders among patients' caregivers is high and influences both burden
      and HRQoL.

PMID- 18709685
TI  - Spectrum of anxiety symptoms in hyperkinesias.

PMID- 18709686
TI  - Manifestations of Parkinson disease differ in association with REM sleep behavior
      disorder.
AB  - REM sleep behavior disorder (RBD) is commonly associated with Parkinson disease
      (PD), but it is unclear whether this association has implications for disease
      manifestations. We evaluated 36 PD patients for the presence of RBD by
      polysomnography. Patients underwent an extensive evaluation by a movement
      disorders specialist blinded to polysomnography results. Severity of motor
      manifestations, autonomic, visual, psychiatric, and olfactory dysfunctions and
      quality of life (QOL) were assessed, and compared using regression analysis that
      adjusted for disease duration, age and sex. Severity of motor manifestations did
      not differ between groups. However, the presence of RBD in PD was strongly
      associated with symptoms and signs of orthostatic hypotension (systolic blood
      pressure lying to standing = -25.7 +/- 13.0 mmHg vs. -4.9 +/-14.1, P < 0.001);
      and orthostatic symptom prevalence = 71% vs. 27%, P = 0.0076). There was no
      association between RBD and other autonomic symptoms. Color vision was worse in
      patients with RBD, but olfactory dysfunction did not differ between groups. The
      prevalence of depression, hallucinations, paranoia, and impulse disorders did not
      differ between groups. Emotional functioning and general health QOL measures were
      lower in those with RBD, but there were no differences between groups on disease
      specific indices or on measures of overall physical QOL. These findings suggest
      that the pathophysiology of RBD and nonmotor manifestations of PD, particularly
      autonomic dysfunction, are linked.

PMID- 18709687
TI  - Subthalamotomy in cervical dystonia: A case study of lesion location and clinical
      outcome.
AB  - Here we report a 63-year-old woman with primary cervical dystonia (CD) whose
      symptoms subsided for more than 30 years following a unilateral stereotactic
      subthalamotomy contralateral to the overactive left sternocleidomastoid muscle
      but then gradually recurred over a period of several months. The aim of the
      present study was to correlate the topography of the stereotactic lesion with the
      long lasting therapeutic effect. High-resolution magnetic resonance imaging and
      subsequent stereotactic analysis were performed to determine the anatomical
      localization of the lesion. The primary coagulation focus comprised the posterior
      subthalamic white matter in the prelemniscal radiation and field H of Forel.
      Neighboring structures were implicated to various extents. It is suggested that
      the posterior subthalamic area, with its abundance of interconnecting fibers and
      related nuclei, represents an effective target for the neurosurgical treatment of
      CD that may be explored further with deep brain stimulation.

PMID- 18709688
TI  - Determinants of persistence with weekly bisphosphonates in patients with
      osteoporosis.
AB  - OBJECTIVE: To evaluate the relationship between the persistent acquisition of
      bisphosphonate (BP) osteoporosis (OP) medication and the following factors: BP
      prescribed; whether BP was first used to replace another non-BP drug for OP;
      patient age; type of drug coverage; specialty of initial prescribing physician;
      and number and type of comorbid diseases. METHODS: Data were acquired from a
      large Canadian public and private claims database, which included information on
      all prescriptions filled, including drug preparation, dose, dosing schedule,
      number of tablets dispensed, and the date of dispensing. A total of 62,897 female
      patients who had initiated weekly BP therapy (risedronate 35 mg once weekly or
      alendronate 70 mg once weekly) for OP between January 1, 2003, and February 28,
      2006 were analyzed, each for 12 months. Persistence rates were determined for 6
      and 12 months post initial prescription. Regression models were used to assess
      the influence of various patient, physician, and drug factors. RESULTS:
      Persistence of BP declined over the first year of BP prescription, to between 60%
      and 74% by 6 months, and between 37% and 59% by 12 months, depending upon a
      variety of factors. The factors that most adversely influenced BP persistence
      were patient age (< 65 vs > or = 65; p < 0.0001); the type of drug coverage
      (public vs private; p < 0.0001); prescribing physician specialty (GP vs
      specialist; p < 0.0001); and number and type of comorbid illnesses (p < 0.01).
      CONCLUSION: Persistence to BP declined significantly over one year. Healthcare
      practitioners should take note of several factors when counselling patients
      taking BP for OP.

PMID- 18709689
TI  - Salivary resistin reflects local inflammation in Sjogren's syndrome.
AB  - OBJECTIVE: To assess the role of resistin in primary Sjogren's syndrome (pSS) and
      its relation to local inflammation. METHODS: Blood and saliva were collected from
      37 patients with pSS (duration of symptoms 12.6+/-1 yrs) and 32 healthy controls.
      Expression of resistin in salivary glands was visualized immunohistologically,
      and levels of resistin were detected by ELISA. Levels of resistin were evaluated
      at baseline and following oral dehydroepiandrosterone (DHEA) treatment (50
      mg/day). The effect of DHEA treatment on the secretion of resistin was assessed
      in vitro in human leukocytes after challenge with insulin and lipopolysaccharide.
      RESULTS: Levels of resistin in saliva were significantly higher in patients with
      pSS than in controls, while circulating levels of resistin were similar in both
      groups. Resistin was expressed in the epithelial cells of striated ducts and in
      the lymphocytic foci. Resistin levels in saliva were related to the intensity of
      inflammation in the minor salivary glands of pSS patients. No changes of the
      levels of resistin in blood or saliva were observed during DHEA treatment.
      Exposure of naive leukocytes to DHEA in vitro induced significant expression of
      resistin compared to nonstimulated peripheral blood mononuclear cells (p=0.031).
      CONCLUSION: We showed that levels of resistin are upregulated locally in the
      salivary glands of patients with pSS; and that the levels of resistin correspond
      to the intensity of lymphocytic inflammation in patients with pSS. We suggest
      that resistin is expressed in the salivary glands of patients with pSS and may be
      a driving factor of local inflammation.

PMID- 18709690
TI  - Prevalence and longterm course of primary biliary cirrhosis in primary Sjogren's
      syndrome.
AB  - OBJECTIVE: To study the prevalence of primary biliary cirrhosis (PBC) and its
      progression in patients with primary Sjogren's syndrome (SS). METHODS: We
      investigated 410 patients with primary SS, without history of liver disease, for
      the presence of PBC based on a retrospective review of clinical, biochemical,
      immunologic, and histologic data. RESULTS: Thirty-six (8.8%) patients had
      cholestatic liver biochemistry. Of them, 21 (5.1%) had positive antimitochondrial
      autoantibodies (AMA) detected by indirect immunofluorescence, while 15 were AMA
      negative. Ten of the 21 AMA-positive patients and 7 of the 15 AMA-negative
      patients were further investigated with liver biopsy, the result of which was
      compatible with PBC in all but one (AMA-negative) patient. Overall, 27 (6.6%)
      patients had definite (n=10), probable (n=11), or AMA-negative (n=6) PBC.
      Pathologically, most PBC lesions were stage 1. Five patients had a second liver
      biopsy, with no significant histological deterioration. CONCLUSION: PBC is a
      rather uncommon development in patients with primary SS. The disease appears to
      be pathologically mild, with a propensity for slow progression, as assessed
      clinically, biochemically, and histologically.

PMID- 18709691
TI  - Th1 and Th2 chemokine serum levels in systemic sclerosis in the presence or
      absence of autoimmune thyroiditis.
AB  - OBJECTIVE: We evaluated contemporarily serum alpha and beta chemokines in
      patients with newly diagnosed systemic sclerosis (SSc) in the presence or absence
      of autoimmune thyroiditis (AT). METHODS: Serum levels of CXCL10 and CCL2
      chemokines, prototypes of the 2 major subclasses (Th1 and Th2), were measured in
      patients with newly diagnosed SSc with (n = 40; SSc-II) or without (n = 50; SSc
      I) AT, in comparison with 50 normal controls (control-I) and 40 AT controls
      without SSc (control-II) (sex- and age-matched). RESULTS: Serum CXCL10 levels
      were significantly higher in control-II, SSc-I, and SSc-II than in control-I (150
      +/- 131, 196 +/- 137, 254 +/- 98, 83 +/- 42 pg/ml, respectively; p < 0.001 for
      all). SSc-I had serum CXCL10 levels significantly higher than control-II (p =
      0.03), and significantly lower than SSc-II (p = 0.04). SSc-II had serum CXCL10
      levels significantly higher than control-II (p = 0.002). Serum CCL2 levels were
      significantly higher in SSc-I and SSc-II than in control-I (378 +/- 192, 403 +/-
      131, 316 +/- 113 pg/ml, respectively; p = 0.03 and p < 0.01, respectively). SSc
      II had serum CCL2 levels significantly higher than control-II (327 +/- 123 pg/ml;
      p = 0.04). CONCLUSION: Our study demonstrates high serum levels of both CXCL10
      (Th1) and CCL2 (Th2) chemokines in patients with SSc, and suggests a prevalence
      of Th1 immune response in the early phase of the disease. A further increase of
      serum CXCL10, but not of CCL2, is observed in SSc patients with AT.

PMID- 18709692
TI  - Statins: potentially useful in therapy of systemic sclerosis-related Raynaud's
      phenomenon and digital ulcers.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is characterized by fibrosis and widespread
      vascular pathology. Raynaud's phenomenon (RP) and digital ulceration are
      prominent manifestations of vascular involvement in SSc. Digital ulcers (DU)
      remain a serious complication, and effective therapy remains elusive. Statins
      display pleiotropic effects on endothelial function that may potentially retard
      vascular injury. We evaluated the potential efficacy of statin therapy in
      endothelial dysfunction and in management of RP and DU. METHODS: Eighty-four SSc
      patients who fulfilled the American College of Rheumatology criteria for
      classification of SSc with secondary RP despite ongoing vasodilator therapy were
      randomized into 2 groups; the first group (n = 56) received 40 mg/day
      atorvastatin for 4 months; the second group (n = 28) received placebo. Seventy
      five healthy volunteers served as controls. Assessment of RP and DU was performed
      monthly. The primary outcome measure was the number of DU. Secondary endpoints
      included the modified Scleroderma Health Assessment Questionnaire Disability
      Index (SHAQ-DI), safety, and tolerability. Measurement of functional status in
      relation to RP included the SHAQ-DI, visual analog scale (VAS) for RP, DU and
      pain scales, and VAS for physician's global assessment for health. Endothelial
      damage markers were also assessed. Endothelium-dependent flow-mediated dilatation
      was measured by high-resolution echo-Doppler ultrasonography. RESULTS: The
      overall number of DU was significantly reduced in the statin group. Among
      patients in the statin group a mean of 1.6 new ulcers developed per patient
      compared to 2.5 new ulcers per patient in the placebo group. There was a
      statistically significant improvement in SHAQ-DI score in patients receiving
      statin versus those on placebo. VAS for RP, DU severity, and pain scales and the
      VAS for physician global assessment improved significantly in the statin group
      compared to the placebo group. Endothelial markers of activation showed
      statistically significant improvement from baseline values in the statin versus
      the placebo group. CONCLUSION: Our results showed that statins retarded vascular
      injury and improved patient function. The findings suggest that statins may aid
      in treating RP and DU in SSc patients. Given the safety and relative low cost of
      statins and good patient tolerability to this class of drugs, statins may be of
      clinical benefit in SSc patients.

PMID- 18709693
TI  - Erythrocyte C4d and complement receptor 1 in systemic lupus erythematosus.
AB  - OBJECTIVE: Complement activation and ineffective clearance of complement-bearing
      immune complexes via erythrocytes contribute to the pathogenesis of systemic
      lupus erythematosus (SLE). Abnormally high levels of erythrocyte C4d and low
      levels of complement receptor 1 (CD35) have been reported in SLE and might have
      diagnostic utility. We investigated whether erythrocyte C4d and complement
      receptor 1 were specific for SLE and whether there was any association with
      disease activity. METHODS: Expression of complement receptor 1 (CD35) and
      complement protein C4d on erythrocytes was measured by indirect
      immunofluorescence and flow cytometry on the same day as the blood draw, in
      patients with SLE, patients with rheumatic disease, and in normal controls.
      RESULTS: Within the SLE population, there was no association with disease
      activity measured by the physician's global assessment or SELENA SLE Disease
      Activity Index, nor with past or current lupus nephritis. Assays were not
      specific for SLE, with higher levels also seen in antiphospholipid syndrome.
      CONCLUSION: Overlap of erythrocyte C4d and CD35 between SLE and other rheumatic
      diseases limits their utility as diagnostic tests. However, longitudinal
      investigation of these assays is warranted, especially given the higher levels in
      some patients with primary antiphospholipid syndrome.

PMID- 18709694
TI  - Relationship between caseload volume and outcome for systemic lupus erythematosus
      treatment: the experience of Taiwan.
AB  - OBJECTIVE: To determine if a physician's experience or hospital caseload volume
      is associated with in-hospital mortality of patients with systemic lupus
      erythematosus (SLE). METHODS: We used data from Taiwan's National Health
      Insurance Research Database covering 2002 to 2004. A total of 8536 hospital
      admissions citing a principal diagnosis of SLE were selected. Hospitals with an
      average of > 50, 26-50, and < 26 SLE cases per year were categorized as high,
      medium, and low-caseload-volume hospitals, respectively. Physician caseload
      volume was defined as low (< 1 SLE case per year), medium (1-3 cases per year),
      and high-volume (> 3 cases per year). Multivariate logistic regression analyses
      employing generalized estimated equations were performed to assess the
      independent association between physician or hospital SLE caseload volume and in
      hospital mortality, after adjusting for other factors. RESULTS: We found that in
      hospital mortality declined with increasing physician caseload volume (3.0%,
      1.0%, and 0.8% for low, medium, and high-volume physicians, respectively), with
      the adjusted odds of in-hospital mortality for patients treated by low-volume
      physicians being 2.681 (p < 0.05) times greater than for patients treated by
      medium-volume physicians, and 3.195 (p < 0.001) times greater than for those
      treated by high-volume physicians. No significant relationship was found between
      in-hospital mortality and hospital SLE caseload volume (p = 0.896). CONCLUSION:
      We concluded that the factor of physicians' experience treating SLE is more
      crucial in determining in-hospital mortality than a hospital's annual SLE
      caseload.

PMID- 18709695
TI  - Arrhythmic risk during acute infusion of infliximab: a prospective, single-blind,
      placebo-controlled, crossover study in patients with chronic arthritis.
AB  - OBJECTIVE: Reports suggest that infliximab (IFX) may be associated with life
      threatening tachyarrhythmias and bradyarrhythmias. We evaluated the prevalence of
      cardiac rhythm disorders during acute infusion of IFX in a prospective, single
      blind, placebo-controlled crossover study of patients with chronic arthritis.
      Effects of the drug on measures of arrhythmia risk such as QT interval and heart
      rate variability (HRV) were evaluated. METHODS: Seventy-five patients with
      spondyloarthritis (SpA; n=55) or rheumatoid arthritis (RA) underwent an
      ambulatory 12-channel electrocardiogram (ECG) recording to monitor cardiac
      arrhythmias, QT interval, and HRV during the infusion of IFX and saline
      (placebo). RESULTS: The occurrence of both tachyarrhythmias and bradyarrhythmias
      was not statistically different during IFX or placebo infusion. During IFX
      infusion, new-onset ventricular tachyarrhythmias had an 8% incidence (2.7% with
      placebo; OR 3.17, 95% CI 0.61-16.26) and were more severe. In these patients,
      mainly with RA, baseline-corrected QT interval and HRV values were significantly
      prolonged and depressed, respectively, in comparison with subjects without such
      arrhythmias. IFX acutely produced a significant shift toward a relative vagal
      prevalence without affecting QT interval measurements. CONCLUSION: New-onset
      cardiac arrhythmias, particularly ventricular tachyarrhythmias, developed during
      IFX infusion, but their incidence did not achieve statistical significance. We
      identified some specific risk factors possibly characteristic of the small subset
      of patients with a higher risk for ventricular arrhythmias. The acute effects of
      IFX on autonomic balance may substantiate the role of the complex interaction
      between autonomic nervous system and inflammation during chronic arthritis.

PMID- 18709697
TI  - What should I do with my left-over medicine?

PMID- 18709696
TI  - SLC22A4 polymorphism and rheumatoid arthritis susceptibility: a replication study
      in a Japanese population and a metaanalysis.
AB  - OBJECTIVE: The SLC22A4 polymorphisms slc2F1 (rs2073838) and slc2F2 (rs3792876)
      are reported to be associated with rheumatoid arthritis (RA) in Japanese, but the
      associations have not been replicated. We assessed the RA susceptibility of
      slc2F1/F2 polymorphisms. METHODS: We conducted a metaanalysis for slc2F1/F2
      polymorphisms to RA susceptibility, which included the replication study of an
      independent Japanese population consisting of 924 cases and 940 controls. A total
      of 9 studies (4 Japanese studies, 5 Caucasian studies) consisting of 8076 cases
      and 6837 controls were included in the metaanalysis. RESULTS: The replication
      study demonstrated significant associations in a Japanese population (OR 1.20,
      95% CI 1.04-1.37, p = 0.0099, in the allelic mode; OR 1.29, 95% CI 1.08-1.55, p =
      0.006, in the dominant mode; p = 0.011 in the trend mode). Significant ethnic
      diversities of allele frequencies of slc2F1/F2 polymorphisms were found (p =
      8.6*10(-8)) between Caucasian and Japanese populations (0.07-0.08 and 0.30-0.32,
      respectively). The metaanalysis demonstrated significant associations for all
      studies (fixed-effect OR 1.11, 95% CI 1.05-1.18, p = 0.00084; random-effect OR
      1.10, 95% CI 1.02-1.19, p = 0.017 in the allelic mode). Although subgroup
      analysis did not detect a significant association within Caucasian studies,
      significant associations were found within Japanese studies (fixed-effect and
      random-effect OR 1.16, 95% CI 1.07-1.25, p = 0.00012 in the allelic mode).
      CONCLUSION: The associations in Caucasian studies were not significant. Since the
      significantly low frequency of the risk allele made statistical power lower in
      Caucasians than in Japanese, whether significant relative risks existed in
      Caucasian populations was inconclusive. The significant relative risks in
      Japanese populations were confirmed.

PMID- 18709698
TI  - The Radio Communication Project in Nepal: a culture-centered approach to
      participation.
AB  - Considerable research has been conducted on the topic of entertainment-education
      (DD), the method of using entertainment platforms such as popular music, radio,
      and television programming to diffuse information, attitudes, and behaviors via
      role modeling. A significant portion of the recently published EE literature has
      used the example of the Radio Communication Project (RCP) in Nepal to demonstrate
      the effectiveness of EE and to argue that EE campaigns can indeed be
      participatory in nature. In this project, we apply the culture-centered approach
      to examine the discursive space created by the RCP and its claim of being
      participatory, A critical examination of RCP discourse brings forth an
      alternative lens for approaching RCP and its participatory claim.

PMID- 18709699
TI  - Community participation, cultural discourse, and health education projects in
      developing areas: the case of the Radio Communication Project in Nepal.

PMID- 18709700
TI  - Adverse effects of prolactin in rodents and humans: breast and prostate cancer.
AB  - Drugs and chemicals shown to induce mammary carcinogenesis in the rat/rodent via
      prolactin excess have traditionally been argued to pose little or no risk to
      humans in a regulatory toxicology context. The basis for this assumption is
      reviewed and placed into context with new evidence in humans that prolactin may
      be a tumour promoter in the breast and prostate. This evidence includes
      epidemiology, patient studies involving endocrine evaluation and molecular
      biology in human cells. It is concluded that hyperprolactinaemia is associated
      with an increase in breast cancer risk in both post and premenopausal women, that
      rat carcinogenicity studies are predictive of the human response, and that in a
      regulatory toxicology context prolactin-induced mammary tumours from nongenotoxic
      drugs and chemicals are an adverse effect that should not be ignored. More
      evidence is required concerning prostate cancer risk but molecular biology
      indicates that prolactin also induces prostate cell proliferation and inhibits
      apoptosis, which are similar to the responses observed in breast cancer cells.

PMID- 18709701
TI  - Bone-protecting effect of Rubus coreanus by dual regulation of osteoblasts and
      osteoclasts.
AB  - OBJECTIVE: Bone loss occurs with increasing age and/or as a secondary occurrence
      to chronic metabolic disease. Certain nutritional and pharmacological, as well as
      nonpharmacologic interventions such as weight-bearing exercise and muscle
      strengthening help prevent bone loss. We examined the effect of the methanol
      extract from the fruit of Rubus coreanus (RCM) on postmenopausal osteoporosis.
      DESIGN: Ovariectomized rats were assigned to sham (negative control), vehicle
      control, positive control, safflower seed 200 mg/kg, RCM 100 mg/kg (RCM 100), RCM
      200 mg/kg (RCM 200), and RCM 400 mg/kg (RCM 400) groups for 10 weeks after the
      operation. Serum biochemistry, histochemistry, immunohistochemistry, and other
      related biomarkers of bone metabolism were investigated. RESULTS: We observed
      that RCM could prevent bone loss by increasing the femur trabecular bone area in
      a dose-dependent manner in ovariectomized rats. The mineral composition of RCM
      contains many more valuable elements, especially potassium, magnesium, and
      vitamins D and B2, than safflower seed. The effect of RCM increased not only
      osteoblast differentiation but also osteoclast apoptosis. In addition, the
      extract of RCM contained in quercetin suggests that the extract of RCM resulted
      in improved aging-related bone loss through an antioxidant effect. CONCLUSIONS:
      The present data provide the first direct in vivo evidence that RCM has a bone
      protecting effect caused by estrogen deficiency, without undesirable side effects
      on the uterus and other solid organs. The beneficial effect of RCM may be
      mediated, at least in part, by dual regulation of the enhancement of osteoblast
      function and induction of osteoclast apoptosis.

PMID- 18709702
TI  - Pituitary volume in psychosis: the first review of the evidence.
AB  - The pituitary gland regulates hypothalamic-pituitary-adrenal (HPA) axis activity
      by secreting adrenocorticotropic hormone (ACTH), and HPA axis abnormalities have
      been described in psychosis. Moreover, the pituitary gland secretes prolactin,
      and some antipsychotics increase the secretion of this hormone. Therefore, it is
      possible that psychosis is associated with an abnormal volume of the pituitary,
      as a consequence of a dysfunction in either or both these hormonal systems. The
      present review of the studies conducted so far clearly indicates that the
      pituitary is a dynamic organ, which changes differently at different stages of
      the psychotic disorder, in response to both the disorder itself and the treatment
      with antipsychotics. Specifically, the pituitary is larger in the months
      immediately preceding or following the psychosis onset, independently from
      antipsychotic treatments. However, following this initial enlargement, the
      pituitary tends to become smaller, as suggested by studies in patients with
      psychosis of at least two years of duration. On top of these dynamic changes that
      are linked to the course of the disorder, antipsychotics, and especially
      antipsychotics inducing hyperprolactinaemia, exert additional enlarging effects
      on pituitary volume. We suggest that the increased pituitary volume associated
      with the development of psychosis is due to activation of the hormonal stress
      response and, specifically, to an increase in the size and number of corticotroph
      cells producing ACTH, while the increased pituitary volume induced by
      antipsychotics is linked to the stimulating effects of these drugs on lactotroph
      cells producing prolactin. Future studies should address these issues that are
      relevant in improving the care of patients with psychosis.

PMID- 18709703
TI  - The sexuality of middle-aged women with a sexual partner: a population-based
      study.
AB  - OBJECTIVE: To evaluate the factors associated with the sexuality of middle-aged
      women with sexual partners. DESIGN: A cross-sectional, population-based study was
      carried out using an anonymous, self-response questionnaire completed by
      Brazilian-born women 40 to 65 years old with 11 years or more of formal education
      who had a sexual partner. Of the 378 women who agreed to participate in the
      study, 219 answered all the questions used for calculation of the sexuality score
      and reported having a sexual partner. The instrument was based on the Short
      Personal Experiences Questionnaire. Seven components were analyzed: satisfaction
      in sexual activities, orgasm, intensity of desire, self-classification of sexual
      life, and frequency of arousal, sexual activity, and sexual fantasies.
      Sociodemographic, clinical, behavioral, reproductive, and partner-related factors
      were evaluated. Poisson multiple regression analysis was performed, and
      prevalence ratios (PRs) with their 95% CIs were estimated. RESULTS: The median
      sexuality score was 9 (range, 2.45-13.77). The prevalence of below-median scores
      was higher in women who lived with their sexual partner (PR = 2.07; 95% CI: 1.17
      3.69), who were in the menopausal transition or were postmenopausal (PR = 1.69;
      95% CI: 1.08-2.65), and who were hypertensive (PR = 1.65; 95% CI: 1.19-2.30).
      Sexual activities involving penetration (PR = 0.48; 95% CI: 0.31-0.73) and a
      score of 6 for satisfaction with partner as a lover (PR = 0.34; 95% CI: 0.20
      0.60) were indicative of a protective effect against poor sexuality. CONCLUSIONS:
      In this cohort, the sexuality of women in midlife was negatively associated with
      the factors of living with a sexual partner, being in the menopausal transition
      or postmenopausal, and being hypertensive. Therefore, greater attention should be
      paid to identifying these factors, and measures should be adopted to minimize
      their repercussions on the sexuality of middle-aged women.

PMID- 18709704
TI  - Recognition of depression among women presenting with menopausal symptoms.
AB  - OBJECTIVE: Depression is particularly prevalent among women in the reproductive
      years. This article reviews research on the risk of depression during the
      transition to menopause and discusses screening methods and management options.
      DESIGN: Systematic literature searches were conducted using MEDLINE (1966 to May
      2007), and all relevant papers published in English were included. RESULTS:
      During the transition to menopause, most women do not experience depression,
      although this period represents a time of increased vulnerability for some women.
      Recent studies suggest that even in women without a history of depression, the
      risk of a new onset of depression is double or more during the menopausal
      transition. Certain patient factors, such as vasomotor symptoms and depression
      during the reproductive years, are commonly seen in gynecologic practice and are
      significant and independent risk factors for developing a new or recurrent
      episode of depression during the menopausal transition. Identifying depression in
      the context of menopausal symptoms may be challenging; however, various
      questionnaires may facilitate diagnosis. Effective short- and long-term
      management of depression is critical, and treatment options include
      antidepressant pharmacotherapy with or without estrogen therapy. Evidence
      suggests that some antidepressant classes have differential efficacy depending on
      menopausal status. CONCLUSIONS: Obstetricians and gynecologists are in a unique
      position to recognize depression in potentially at-risk patients. Proactive
      screening and diagnosis of depression are critical for successful treatment
      outcomes. Additional studies are needed to evaluate the effects of menopausal
      status on antidepressant response and to identify new, safe, and efficacious
      treatment options for depression during perimenopause.

PMID- 18709706
TI  - ECC: quality care or supervised neglect?

PMID- 18709705
TI  - Ovarian dysfunction and the premenopausal origins of coronary heart disease.
AB  - OBJECTIVE: The menopausal loss of cyclic ovarian function is believed to
      contribute to coronary heart disease (CHD). However, ovarian function varies
      substantially throughout the premenopausal years, with disruptions in hormonal
      activity ranging from mild to profound. Here we propose our "precocious
      acceleration" hypothesis, which holds that to the extent cyclic ovarian function
      affords protection against CHD, even mild ovulatory abnormalities in young women
      will accelerate development of this disease. DESIGN: Data relating to the
      expression and incidence of premenopausal ovarian dysfunction in women and its
      relationship to CHD are reviewed. Also reviewed are the results from experiments
      conducted with socially housed cynomolgus monkeys (Macaca fascicularis), focused
      on the causes, occurrence, and pathobiological sequelae of premenopausal ovarian
      dysfunction. The implications of the foregoing material for understanding the
      health of peri- and postmenopausal women are then considered. RESULTS:
      Epidemiological and clinical studies indicate that common premenopausal
      reproductive abnormalities (manifested along a continuum from mild subclinical
      alterations to complete suppression) are associated with increased risk of CHD.
      This increased risk is probably mediated by different pathways, depending on
      whether the reproductive deficits relate to hypoestrogenemia (functional
      hypothalamic anovulatory syndrome) or hyperandrogenemia (polycystic ovary
      syndrome). Furthermore, although clinically obvious expressions of these
      syndromes affect perhaps 10% of premenopausal women, evidence suggests that a
      much larger number may experience subclinical dysfunction capable of increasing
      CHD risk. CONCLUSIONS: Epidemiological data and systematic studies in nonhuman
      primates provide initial support for the precocious acceleration hypothesis,
      suggesting that efforts to protect the health of postmenopausal women would best
      begin during the premenopausal years.

PMID- 18709707
TI  - Medical doctors profile in Ethiopia: production, attrition and retention. In
      memory of 100-years Ethiopian modern medicine & the new Ethiopian millennium.
AB  - BACKGROUND: Although the practice of western medicine in Ethiopia dates back to
      the time of King Libne Dengel (1520-1535), organized and sustainable modern
      medical practice started after the battle of Adwa (1896). OBJECTIVE: To review
      hospitals construction, medical doctors production and attrition, and to suggest
      alternative medical doctors retention mechanisms in the public sector and
      production scale up options. METHODS AND MATERIALS: In this article, 100 years
      Ethiopian modern medical history is revised from old and recent medical
      chronicles. Until December 2006 primary data was collected from 87 public
      hospitals. Much emphasis is given to medical doctors profile (1906-2006),
      hospitals profile (1906-2005), medical doctors to population and hospitals ratio
      (1965-2006), Ethiopian public medical schools 42 years attainment (1964-2006),
      annual attrition rate (1984-2006), organizational structure of medical faculties
      & university hospitals, medical doctors remuneration by the Ministry of Health
      (MOH), Ministry of Education (MOE), NGOs and private health institutions. This
      article also addresses the way forward from physician training and retention
      perspectives, multiple alternate mechanisms to increase physicians' motivation to
      work in government institutions and reveres the loss. Medical doctors production
      scale up option is also given much emphasis. Most data are presented using line
      and bar graphs. RESULTS: Literature review showed that the first three hospitals
      were constructed in 1896 (Russian hospital), 1903 (Harar Ras Mekonnen hospital)
      and 1906 (Menelik II hospital). In 2005, 139 hospitals (87 public and 52 others)
      were reported. Remarkable hospital construction was done between 1935 and 1948,
      and recently between 1995 and 2005; however, in the latter case, private
      hospitals construction took the lions share. By the time MOH was established
      (1948), 110 Ethiopian and expatriate medical doctors were working, mainly in the
      capital, and 46 hospitals constructed. Physician number increment was very slow
      till 1980 at which time it started to get doubled every five years and reached
      peak (1658 medical doctors of all type) in 1989 in the public sector. As there
      was sharp increment in physician number, on the contrary, there was sharp decline
      in the last 15 years (1990-2006) to nadir 638 doctors in 2006 in the public
      sector. The last 25 years of Ethiopian modern medical history, in reference to
      physician number, forms a triangle with the lower and upper base 1980 and 2006,
      respectively. Since MOH of Ethiopia started registering health professionals with
      qualifications in 1987, 5743 (76.5% Ethiopian and 23.5% expatriate) medical
      doctors were registered for the first time. Out of these, 3717 were general
      practitioners. The three prestigious medical schools (Addis Ababa, Gondar, Jimma)
      were established in 1964, 1978 and 1984, respectively. Since establishment till
      2006, about 3728 medical doctors were graduated with MD degree from the three
      medical schools. Addis Ababa university medical faculty alone graduated 1890
      general practitioners (1964-2006) and 862 clinical specialists (1979-2006). In
      the 23 years period (1984-2006), the highest and lowest physician to population
      ratios in the public sector were found to be in 1989 (1:28,000) and 2006
      (1:118,000), respectively. In 2006, the physician to population ratio in Amhara,
      Oromia and SNNPR regional states was computed to be 1:280,000, 1:220,000, and
      1:230,000, respectively. The physician deficit analysis in the last 23 years in
      relation to the WHO standard for developing countries (1:10,000) revealed the
      lowest record at the national and regional states in the last 12-years. Average
      physician to hospital ratio in five regional states in December 2006 was 3.6
      (Tigray), 4.3 (Amhara), 6.1 (Oromia) and 5.3 (SNNPR). As the December 2006 direct
      interview with 76 public hospitals outside Addis Ababa showed, there was no
      specialist in 36 hospitals and no doctor at all in 3 hospitals. Seven public
      hospitals located in big regional states' town took the lions share of medical
      doctors. In short, in December 2006, 80.3% of regional hospitals were equipped
      with 0-2 specialists of one kind, and in 48.7% there were 0-3 General
      practitioners. Highest medical doctors annual attrition rates (20%-54.3%) were
      found in 1991-1992, 1998, 2002-2006. In general, in 20 years period (1987-2006),
      73.2% of Ethiopian medical doctors left the public sector mainly due to
      attractive remuneration in overseas countries and local NGOs/private sectors. The
      number of postgraduate programme in Addis Ababa, Jimma and Gondar medical schools
      in December 2006 was 22, 12 and 3, respectively. The total number of fully
      employed academic staff of the medical schools in declining order was Addis Ababa
      181, Gondar 118, Jimma 71, Hawassa 63 and Mekele 52: those with second degree and
      above being 97.2%, 35.6%, 90.1%, 55.6% and 15.4%, respectively. Currently (2006),
      there are about 416 clinical residents in 3 medical schools. CONCLUSION: High
      annual attrition rate, fast population growth, governmental and nongovernmental
      health institution expansion, low production and increased postgraduate
      enrollment in the last 3-4 years contributed for extremely low physician-to
      population ratio in Ethiopia. Although the Ethiopian government and private
      sector worked and achieved much on health infrastructure construction and
      midlevel health professionals training, it does not appear that medical doctors
      retention mechanisms are sorted out so far. As a result, even despite salary
      equivalent top up payments in some regions, more than 80% of public hospitals
      outside Addis Ababa were found ill-equipped with the most important human element
      -physicians. This implies that the push factors may not invariably correlate with
      remuneration. RECOMMENDATION: It is high time that the government discusses the
      possible solutions among health professional associations/societies and other
      health stakeholders, and apply concrete medical doctors retention mechanisms
      before the public medical schools and hospitals dry off doctors. Among actions to
      be undertaken from the current Ethiopian perspective: providing land plot for
      physicians for residential house construction, giving priority to physicians in
      providing low cost houses, low interest or interest free loan for residential
      house construction and automobile procurement, allowing duty free automobile
      procurement, improving the fully employed academic staff taxation system,
      approving the different remuneration options proposed, adopting the other
      countries experience of dual employment to academic staff working in teaching
      hospitals, modifying the academic rank promotion based on year of training, for
      university hospitals either establishing hospital organizational structure in the
      Ministry of Education or letting them be under MOH, establishing joint
      appointment (mutual beneficiary) agreement between medical schools and local
      hospitals, directing donors and stakeholders to work on the line of reducing
      internal and external medical doctors brain drain, making independent MOH and
      higher institutions from Civil Service Agency are proposed as short term
      solutions. Retention as a strategy & production as a programme, medical doctors
      production scale up options are proposed as a long term solution to achieve
      physician to population ratio of 1:15,000. and 1:8,000 by the year 2015 and 2020,
      respectively.

PMID- 18709708
TI  - [Hygiene of handwashing].

PMID- 18709711
TI  - [Violence and discord in personal relations in Mexico City at the end of the 18th
      century].

PMID- 18709712
TI  - The wet nurses of Jocotenango: gender, science, and politics in late-colonial
      Guatemala.

PMID- 18709714
TI  - Procuring mothers, sacrificed daughters and "helpful" policemen: the elite
      prostitutes as family breadwinner in eighteenth-century Paris.

PMID- 18709717
TI  - Bibliography. Current world literature. Movement disorders.

PMID- 18709716
TI  - Computational Systems Bioinformatics Conference 2007. Introduction.

PMID- 18709718
TI  - [The life of Prof. Andrzej Wall].

PMID- 18709719
TI  - [Cooperation of Polish and German orthopedists as a part of the Circle od
      Friends, 1995-2008. In memory of Prof. Johannes Breitenfelder].

PMID- 18709720
TI  - [Replay to article: "Professional autonomy od physical therapists based on
      medical education in New Zealand" (Ortop Traumatol Rehabil. 2008 10(2)].

PMID- 18709721
TI  - [Sensibility and educating a child during the Batavian period: the private
      journal of Otto van Eck, 1791-96. Part 1].

PMID- 18709722
TI  - "Subtilized into savages": Edmund Burke, progress, and primitivism.

PMID- 18709723
TI  - Bibliography. Current world literature. Reproductive endocrinology.

PMID- 18709724
TI  - "The misguided greed of peasants"? Popular attitudes to the environment in the
      revolution of 1789.

PMID- 18709725
TI  - Retraction to "A recommended specification for heavy vehicle rear underrun
      guards" [AAP 39/4(2007)696-707].

PMID- 18709726
TI  - Complications and adverse events in Chinese trials of acupuncture.

PMID- 18709727
TI  - Professor Sven Andersson in memoriam--the Swediah father of acupuncture.

PMID- 18709728
TI  - [Case of pulmonary nocardia infection complicated with microscopic polyangiitis
      during its course].

PMID- 18709729
TI  - [Change in serum concentration of itraconazole according to its dosage form].

PMID- 18709730
TI  - [Efficacy of itraconazole injections for treatment of febrile neutropenia].

PMID- 18709731
TI  - [Usefulness of sputum galactomannan in diagnosis of pulmonary aspergillosis].

PMID- 18709732
TI  - [Prophylactic use of oral itraconazole solution for febrile neutropenia
      associated with hematologic malignancies].

PMID- 18709733
TI  - Practical systems biology. Preface.

PMID- 18709734
TI  - Bioinformatic approaches to biological systems.

PMID- 18709735
TI  - Cell sampling and global nucleic acid amplification.

PMID- 18709736
TI  - Methods of proteome analysis: challenges and opportunities.

PMID- 18709737
TI  - Vertical systems biology: from DNA to flux and back.

PMID- 18709738
TI  - Using mathematical models to probe dynamic expression data.

PMID- 18709739
TI  - Gene regulatory network models: a dynamic and integrative approach to
      development.

PMID- 18709740
TI  - Spatio-temporal dynamics of protein modification cascades.

PMID- 18709741
TI  - Intracellular signalling during bacterial chemotaxis.

PMID- 18709742
TI  - Modelling the mammalian heart.

PMID- 18709743
TI  - Modelling root growth and development.

PMID- 18709744
TI  - Focus on rural health. Preface.

PMID- 18709745
TI  - Diabetes care among rural Americans.
AB  - The prevalence of diabetes in the United States is higher among those living in
      rural/ nonmetropolitan statistical areas than in urban centers. Managing this
      complex chronic illness is complicated by factors such as limited access to care,
      low socioeconomic status, aging, and membership in a racial or ethnic minority
      group. A review of the literature was conducted focusing on research about rural
      Americans with diabetes by searching databases of CINAHL, PubMed, and MEDLINE,
      and selecting articles in English that were published between 2000 and 2007.
      Search terms included: nursing, research, rural, rural nursing, rural health
      services/programs, and diabetes care. Additional search strategies included
      journal hand searching and networking. Twenty-six research reports were found and
      included qualitative and quantitative methods and program evaluations. All
      regions of the United States were represented except the Northwest. The vast
      majority of research reports were of descriptive studies (n = 16), with program
      evaluation reports (n = 7) and studies testing an intervention (n = 3) also
      represented. The quality of each study is examined and summarized.

PMID- 18709746
TI  - Matters of the heart: cardiovascular disease and rural nursing.
AB  - Cardiovascular disease (CVD) is the leading cause of death in the United States
      and around the world. Most of the work done on CVD among rural populations uses
      mortality versus prevalence rates because prevalence data for rural populations
      is difficult, if not impossible, to find in national data sets as currently
      published. Cardiovascular disease is a significant threat to rural dwellers and
      those in rural nursing need evidence on which to base their practice. This
      chapter provides an examination of the CVD literature as it relates to rural
      populations with an emphasis on studies that include or are limited to rural
      women as subjects. Topics reviewed included: awareness and symptoms of heart
      disease among women, heart failure (HF) in rural women, hypertension (HTN) in
      rural areas, stroke in rural populations, quality care in acute myocardial
      infarction (MI) in rural facilities, mortality and CVD, and CVD risk factors in
      rural populations. The authors reviewed 134 research articles published between
      2000 and 2007. Overall, the CVD research literature in rural populations has
      small sample sizes, except for epidemiologic studies, and tends to be descriptive
      in nature. There is a dearth of literature on prevalence among rural populations
      from a national perspective and little is written on interventions to reduce CVD
      risks and physiological markers that include large samples from rural
      populations. Future nursing research on CVD in rural populations needs to move
      beyond the descriptive to intervention studies, which need to be robust in power
      to guard against Type II errors.

PMID- 18709747
TI  - Intimate partner violence in rural environments.
AB  - The purpose of this chapter is to review nursing and other research related to
      rural intimate partner violence. The author presents a review of research in the
      area of intimate partner violence in the rural setting. The findings indicate
      that there is limited nursing research related to intimate partner violence in
      rural communities. The review describes the prevalence and types of abuse, the
      rural service issues, and the consequences of battering. The chapter also
      discusses the health implications of violence in the rural setting. The author
      concludes with a presentation of a research agenda for nursing research in rural
      environments.

PMID- 18709748
TI  - Hospital-based emergency nursing in rural settings.
AB  - In 2006, the Institute of Medicine (IOM) released a series of reports that
      highlighted the urgent need for improvements in the nation's emergency health
      services. This news has provided new energy to a growing body of research about
      the development and implementation of best practices in emergency care. Despite
      evidence of geographical disparities in health services, relatively little
      attention has been focused on rural emergency services to identify environmental
      differences. The purpose of this chapter is to summarize the contributions of
      nursing research to the rural emergency services literature. The research
      resembles a so-called shotgun effect as the exploratory and interventional
      studies cover a wide range of topics without consistency or justification.
      Emergency nursing research has been conducted primarily in urban settings, with
      small samples and insufficient methodological rigor. This chapter will discuss
      the limitations of the research and set forth an agenda of critical topics that
      need to be explored related to emergency nursing in rural settings.

PMID- 18709749
TI  - Building the rural mental health system: from De Facto system to quality care.
AB  - About 20% of Americans live in rural America, yet the rural mental health
      infrastructure has yet to be firmly established. This is due in part to a
      pervasive belief about the tranquility of rural places and the relatively stress
      free environment that they produce. In this chapter an adaptation of the Rural De
      Facto Mental Health Systems Model produced by Fox and her associates at the
      Southeastern Rural Mental Health Research Center is presented and used to
      organize the scientific state of the field of rural mental health services
      research. As many nurses have stood at the forefront of that research, the
      research of several prominent rural mental health nurse researchers and the
      innovative research they have produced are reviewed. The chapter concludes with a
      discussion of research that is needed to move the science of rural mental health
      services research forward, as well as a discussion of policy initiatives that may
      be necessary to foster the development and implementation of that research
      agenda.

PMID- 18709750
TI  - Improving the quality of rural nursing care.
AB  - The purpose of this chapter is to review the literature on quality of care in
      rural areas. Keywords related to rural quality of care were used to search CINAHL
      and MEDLINE databases for articles published between 2005 and 2007 (limited to
      studies occurring in the United States). The review consisted of a total of 46
      articles. Limitations include inconsistent definitions of rural, the use of only
      articles available to the reviewers, an unclear understanding of the context of
      many of the studies, and lack of a clear operational definition of quality. The
      studies were grouped and discussed according to quality of workforce, practice,
      treatment, interventions, and technology in rural areas. Each study's
      contribution to the understanding of quality health care in rural areas and to
      determining what was effective in improving staff, patient, or organizational
      outcomes in rural areas was considered. This chapter also offers a discussion of
      ethical issues and data quality in rural research. Issues for future research
      include a focus on patient safety, mental health issues, and the use of
      technology to improve quality of care in rural areas. Future research should also
      focus on demonstration studies of model applications. The nursing profession has
      a unique opportunity to conduct research that will contribute to the development
      of knowledge that will ultimately improve the quality of health and health care
      for individuals in rural communities.

PMID- 18709751
TI  - Nursing patient safety research in rural health care settings.
AB  - Adverse events occur in virtually all health care arenas, and while rural health
      care settings are no exception, these facilities often face unique financial
      burdens and personnel shortages. That may hamper patient safety efforts. Many of
      the interventions recommended to improve patient safety have largely been based
      on research conducted in urban hospitals. This chapter demonstrates the extent
      and type of nursing research being conducted to advance rural-specific patient
      safety research. The studies were conducted in various settings, with topics
      ranging from error reporting in hospitals to safety screening in the community.
      Limitations of these works are discussed, and the chapter offers guidance for a
      future nursing research agenda to include the need for interdisciplinary
      research; cross-national and international collaboration; and, at a minimum, the
      necessity for nurse researchers to sample rural hospitals in larger studies of
      patient safety.

PMID- 18709752
TI  - Conducting culturally competent rural nursing research.
AB  - The face of America is changing. In efforts to provide services to and meet the
      needs of consumers of different ethnicities and cultures, cultural competence has
      become a driving force not only in health care but also in business, education,
      and research. Lack of cultural competence among caregivers has been linked to
      health disparities, decreased client satisfaction, and decreased client adherence
      to recommended medical regimens. The depth of rural research in general, and by
      nurse researchers focusing on rural cultural groups in particular, is limited.
      This chapter focuses on conducting rural nursing research with rural cultural
      groups, highlights methodological issues that are commonly encountered with rural
      populations, and proposes strategies to address them. Addressing methodological
      challenges will contribute to the limited knowledge base related to culture and
      ethnicity in rural nursing research.

PMID- 18709753
TI  - Establishing the public's trust through community-based participatory research: a
      case example to improve health care for a rural Hispanic community.
AB  - This chapter describes the contextual nature of contemporary rural America to
      provide the background for the case example of a 4-year community-based
      participatory research project to enhance community capacity building in a rural
      New England community with a large Latino/Hispanic population. The changing
      nature of rural populations and implications for rural health care and nursing
      research are discussed.

PMID- 18709754
TI  - Rural health nursing research review: global perspectives.
AB  - The CINAHL and MEDLINE databases were used to conduct a review of international
      rural nursing research published between 2003 and 2007. In total, 41 articles
      were reviewed and organized based on the United Nations Human Development Index,
      which categorizes countries based on development status. Critical review of
      international rural nursing research yielded three major organizational themes:
      clinical issues, aspects of nursing practice, and nursing and health policy
      research. Despite the variety in international locale of the research, these
      themes and other common findings emerged. The need for increased access to
      specialized nursing knowledge, resources, and support is an ongoing issue facing
      nurses in rural and remote settings.

PMID- 18709755
TI  - [Life events in correlation with the intensity and entity of depressive
      disorder].
AB  - The article deals with types of life events preceding the onset or repeated
      episodes of endogenous (major) depression, as well as their influence on the
      intensity of depressive symptoms in hospitalized patients. It was found that
      events with intensive long-term contextual threat more often precede the first
      episode than the repeated depressive episodes (4 cases), although the difference
      was not statistically significante (F=0.12 F>0.05). Loss (death or separation
      from a close person) is an event. Recent in closeds relation with the onset of
      depressive disorder and far more often procedes the first than the repeated (1
      case) episode. The difference was statistically significant (F=0.018 P<0.05). It
      seems that, due to the exhaustion of defensive mechanisms, a mild stress is
      sufficient to provoke a repeated episode of depression. The intensity of
      depressive symptoms was not indicated by the stress impact of the experienced
      life events both in the onset (t=0.039 P>0.05) and the repeated episode of
      illness.

PMID- 18709756
TI  - [Angle of caudal declination of the ribs and its changes in children with pectus
      excavatum].
AB  - The study of the angle of caudal declination of the ribs in 19 children aged 5
      years, and in 23 children aged 8 years undergoing pectus excavatum repair,
      established that children with deformity had significantly wider angle compared
      to children of the same age without chest deformity. The angle of declination was
      not significantly changed 3 years after the operation. Thus it was concluded that
      subperichondral excision of the rib cartilage and osteotomy of the sternum led to
      fixed chest position. These data can explain persistent pulmonary dysfunction of
      the restrictive type in spite of successful aesthetic correction of the
      deformity.

PMID- 18709757
TI  - [Direct immunofluorescence technique in the diagnosis of Chlamydia nongonococcal
      urethritis].
AB  - We evaluated the direct immunofluorescence technique in the diagnosis of
      nongonococcal urethritis caused by Chlamydia trachomatis. Urethral swabs taken
      from 210 patients with urethritis were investigated by this method. The results
      were compared with the results obtained from the same patients by conventional
      method - cell culture. Of 210 patients with nongonococcal urethritis Chlamydia
      trachomatis was established in 114 (54.3%) cases by cell culture method and in
      113 (53.8%) by direct imunofluorescence method. Compatibile results were found in
      195 (92.8%) of cases. A good coorelation (Rxy = = 0.86) between the results
      obtained by the examined method and the referentain vas found. The direct
      immunofluorescence technique is a specific and sensitive method in the diagnosis
      of chlamydia urethritis. The direct immunofluorescence technique is an
      alternative diagnostic method of the harder and lengthy cell procedure. It is
      very important in routine clinical practice.

PMID- 18709758
TI  - [Drug addiction and working capacity].
AB  - The article deals with the attempt of determining the working capacity in
      previously employed drug-addicts and of evaluating the effect of the disease on
      their working capacity and their psycho-physical damage due to chronic drug
      poisoning.

PMID- 18709759
TI  - [Characteristics of renal failure in chronic liver disease].
AB  - The aim of this study was to establish the characteristics of renal failure in
      patients with cirrhosis and compare their laboratory data on blood and urine with
      those of patients with chronic renal failure without liver disease; and then to
      correlate the data of patients with cirrhosis and renal failure with that of
      patients with cirrhosis without renal failure in relation to liver function There
      were three groups of patients: group A - patients with cirrhosis and renal
      failure; group K1-patients with cirrhosis without renal failure; and group K2
      patients with chronic renal failure. The parameters of renal and liver function
      were also compared. The laboratory data on blood and urine in patients with
      cirrhosis and renal failure revealed characteristics of prerenal failure in a
      higher degree (functional renal failure). When liver failure was concerned there
      was no difference between patients with cirrhosis and renal failure and subjects
      with cirrhosis and no renal failure. The degree of renal failure was not always
      the same regarding the degree of liver failure although they can sometimes
      paralell.

PMID- 18709760
TI  - [Tumours as cause of eyeball loss in adults].
AB  - Causes of eyeball loss in patients over 15 years of age are analyzed, over the
      period from the beginning of 1966 to the end of 1987. Data from the files of the
      Ophtalmopathologic Laboratory, Department of Eye Diseases, UCC, Belgrade, were
      used. In the period of 22 years 2067 eyeballs were enucleated, the procedure
      being necessitated by tumurs, injuries and other disease in 834, 722 and 511
      cases, respectively. The analysis focuses on tumours as the cause of eyeball
      enucleation. Malignant melanoma of the choroid was noted in 700 cases, skin or
      conjunctival carcinoma in 117 cases, metastatic tumours of the choroid in 9
      cases, and other types of tumours in the remaining 8 cases. At the beginning of
      the period (1966-1987) tumours were the third most common cause of enucleation,
      just after diseases and injuries. However, in the last ten years there is a
      continuous increase in the number of enucleations performed for ocular tumours.
      Thus tumours have become the most common cause of enucleation. The results show
      that the number of enucleations is related to the age of the patients. Male to
      female ratio was uniform in all age groups.

PMID- 18709761
TI  - [Serum immunoglobulin values in children with altered spirometric values].
AB  - The authors present values of immunoglobulins IgA, IgM, IgG and IgE in 40 pupils
      at Sabac, who were exposed to high aeropollution and in whom spirometric
      pulmonary functions (vital capacity, FEV1 and FEV1/PVC relation) were under the
      normal or at its upper limit. Frequent respiratory diseases, sometimes followed
      by wheezing, were observed in these children. The aim of the study was to detect
      a possible predisposing factor responsible of these conditions. This was done
      with the control examinations of immunoglobin values when atopic constitution
      (IgE) or immunodeficency should be detected. IgG values were, however, within the
      normal. Thus, the atopic role in the onset of these respiratory disorders was
      excluded. High-degree aeropollution was cited as the main cause of frequent
      respiratory diseases and low spirometric values of the pulmonary function.

PMID- 18709762
TI  - [Catheters in patients with acute leukaemia].
AB  - The authors present kinds and frequency of complications during the use of
      central venous catheters in adults with acute leukaemia. During the-year
      prospective study of 35 central venous catheters placed in 33 consecutive
      patients entering intensive leukeamia therapy 30 complications were registered.
      The complications were as follows: early complication (10%); local inflammation
      (23%); partial thrombosis (23%), complete thrombosis (19%); catheter-related
      sepsis (10%), and miscelaneous (15%). All catheters with complete thrombosis were
      successfully recanalised with small doses of streptokinase (less than 40,000
      units) and fresh frozen plasma. Frequency of complications can be decreased by
      preventive measures such as: holding transitoriness oaf catheters, asepsis and
      antisepsis, and introducing contemporary Hickman catheters with infusion pumps.

PMID- 18709763
TI  - [Erythropoietin].
AB  - New data on erythropoietin and regulation of erythropoiesis are presented; the
      possibility to treat anaemia in patients with chronic renal disease by
      erythropoietin is stressed.

PMID- 18709764
TI  - [Acute poisoning by herbicide compounds].
AB  - The increasing incidence of human poisoning by herbicides arises either from
      their wide (and sometimes irrational) agricultural use or abuse for suicidal
      (rarely homicdal) purposes. From the viewpoint of clinical toxicology the
      intoxisations by dipyrridiles, dinitrophenols and dervivates of phenoxysarbonic
      acids are of great importance. Due to high acute toxicity of these herbicide
      compounds accidental or intentional poisonings are mainly characterized by
      serious morphological damages and complex functional disorders of almost all
      parenchimatous organs. In spite of urgent treatment and intensive care measures
      the mortality rate in these intoxications is still high. Based on personal
      clinical experience in herbicide intoxication and data from literature, the
      mechanisms of their action, clinical features, current treatment regimen and
      prognostic elements are reviewed.

PMID- 18709765
TI  - ["One and a half syndrome" caused by lateral pontine haemorrhage].
AB  - "One and a half syndrome" is an internuclear ophthalmoplegia combined with
      lateral gaze palsy on the same side. It is caused by ipsilateral lesion of the
      caudal part of pontine dorsal tegmentum - medial longitudinal fasciculus and
      paramedian pontine reticular formation or/and abducens nucleus. Usually it is of
      vascular origin and it can be a sign of lateral pontine haemorrhage. We described
      a patient with "one and a half syndrome" caused by spontaneous hypertensive
      hemorrhage in the lateral pontine legmentum which was visualised by brain CT
      scanning.

PMID- 18709766
TI  - [Joubert's syndrome].
AB  - In 1969 a new syndrome was described by Joubert et al. It is a very rare syndrome
      as only about 30 cases have been reported, and none in Yugoslavia. The main
      clinical characteristics are as ballows. - Disturbed respiratory rhythm
      alternating periods of hyperapnea and apnea) which tend to disappear as the child
      grows; - Abnormal eyemovements (jerky, rotatory, pendular); - Mental retardation
      (usually severe and which deteriorates with the age); and - Ataxia (sometimes
      also severe). The main neuropathological finding is dysplasia of the vermis
      cerebelli. Typical CT - findings consist of a very large cisterna magna
      communicating with the fourth ventricle. The prognosis of the syndrome is poor:
      half of the patients die within the first three years. Early recognition of the
      syndrome is important in view of prognosis and genetic counselling. The authors
      report a first case of Joubert's syndrome in Yuhoslavia, and review the relevant
      literature on this subject.

PMID- 18709767
TI  - [Invasive pulmonary aspergillosis during the treatment of acute leukaemia (3 case
      report)].
AB  - The authors describe 3 patients with confirmed diagnosis of invasive pulmonary
      aspergillosis (IPA) during the treatment of acute leukaemia in the period July
      September 1987. High statistic significance of previous incidence of the disease,
      high fungal contamination and epidemiologic relationship between cases point at
      the epidemic. All patients were treated with amphotericin B; two patients died
      and the third was cured with intensive 6-month--treatment of amphotericin B in
      the total dose of 4 grams. It is necessery to introduce amphotericin B in therapy
      of every febrile patient in prolonged granulocytopenia not responsive to 2
      combinations of antibiotics after 4 days and persistently looking for radiologic,
      microbiologic, serologiic and histopathologic evidence of aspergillus infection.
      In addition to prolonged granulocytopenia high contamination of air with
      aspergilli is necessery for an epidemic of invasive pulmonary aspergillosis.

PMID- 18709768
TI  - [Mixed colon tumour: leiomyoma-haemangioma].
AB  - Leiomyoma and heamangioma of the colon are extremely rare tumours. Only 27 cases
      were published in world literature up to 1954. A few new were published after
      that period. We describe a 46-year-old man with 3-months-history of occlusive
      symptoms in whom during the operation for complete colon obstruction mixed colon
      tumour (leiomyoma-haemangioma) was found, 10 cm distal to hepatic flexure. The
      tumour was of intraluminal pedunculated type", 7 cm in maximal diameter. Four
      enlarged, firm lymph nodes in the mesocolon close to the tumour were found. Right
      colectomy was carried out as the most resonable procedure. Histopathology showed
      leiomyoma of the colon with massive fibrous tissue, degeneration, bleeding of the
      tumour and many dilated blood vessels, so that its pedunculated part resembled a
      haemangioma. No sign of malignancy was found. The recovery of the patient was
      normal, and he stayed symptom-free, with normal small bowel function, clinical
      and laboratory data.

PMID- 18709769
TI  - [Fibrosarcoma of the pancreas].
AB  - Fibrosarcoma of the pancreas is a very rare tumour. Its localisation in any part
      of the pancreas causes various dominant symptoms. Tumour is often enormously
      enlarged, very vascular, often with central necrosis and penetration into the
      gastric wall causing ulcers and bleeding. Prognosis of the tumour is not always
      bad due to low malignancy. The authors describe a 53-year-old woman with
      fibrosarcoma of the pancreatic body. The first symptom was an epigastric pain
      when subcardial gastric ulcer was diagnosed and conservatively treated. One year
      later a huge palpable epigastric tumour was found with massive gastrointestinal
      bleeding as a dominant symptom. Gasher was dislocated from the less curvature
      side by the tumour. During the operation a great, solid and highly vascular
      tumour was removed, 2100 grams of weight and 15 cm in diameter Subtotal gastric
      resection with Billroth II anastomosis was done because of the infiltration of
      the posterior gastric wall and bleeding ulceration. Histopathology showed the
      first stage malignany of pancreatic fibrosarcoma. The patient is symptom free,
      without local recidivation and distant metastases over 3 years after the
      operation.

PMID- 18709770
TI  - [Severe postoperative complications in colorectal surgery for cancer. Incidence
      related to the techniques employed: open versus laparoscopic colectomy].
AB  - In this preliminary retrospective study, severe postoperative complications
      following surgery for colorectal cancer were analysed, comparing the results
      obtained with open versus laparoscopic colectomy. Over the period 2005-2007, 50
      patients (29 female, 21 male; age range: 32-85 years) underwent surgical
      treatment for colorectal-anal cancer. Twenty-nine (58%) were submitted to the
      traditional open technique and 21 (42%) to the laparoscopic technique. No
      mortality occurred with either technique. None of the cases submitted to
      laparoscopy presented anastomotic dehiscence or severe intraoperative bleeding.
      In the group submitted to open surgery, 3 cases of severe complications occurred
      (10.3%), consisting in acute faecal peritonitis due to immediate dehiscence of
      the colorectal anastomosis; angulation of the intestinal loop with
      microdehiscence of the ileo-colic anastomosis; and pulmonary embolism. In the
      group submitted to laparoscopic surgery, 2 cases of severe complications occurred
      (9.5%), consisting in enterorrhagia due to haemoperitoneum; and intrafascial
      haematoma due to haemorrhage of the epigastric artery. The overall complication
      rate was 10%, corresponding to the minimum values reported in the literature. No
      statistically significant difference was observed in the incidence of these
      complications with the two methods employed. A very low incidence of minor
      complications was observed, limited to repercussions on the postoperative course.
      Furthermore, the laparoscopic technique led to early canalisation, a reduction in
      hospital stay, less need of drugs (antibiotics and pain killers) and better
      aesthetic results. The advantages obtained with the laparoscopic technique, with
      no significant differences in severe complications, indicate that this approach
      is preferable to the traditional technique in colorectal surgery for cancer.

PMID- 18709772
TI  - [Local excision of giant rectal polypoid neoplasms].
AB  - Local excision is the best therapeutic option for giant adenomas of the rectum.
      Parks technique for lower rectal lesions and the T.E.M. technique for lesions
      localised in the middle and upper rectum offer exceptionally good exposure,
      allowing radical excision in the case of early low-risk T1 adenocarcinomas (well
      or moderately differentiated [G1/2] without lymphovascular invasion [L0]). From
      July 1987 to March 2006, 224 patients were treated by local excision for rectal
      lesions in our department. In 48 patients (21.4%) a large sessile benign lesion
      was diagnosed preoperatively. In 3 patients with a preoperative diagnosis of
      severe dysplasia (Tis) final pathology showed adenoma and for this reason they
      were included in our study group. A total of 51 patients with giant preoperative
      benign lesions were treated by local excision (Parks technique, T.E.M. or both).
      Twenty-five (49%) patients had a definitive diagnosis of adenocarcinoma: in situ
      (pTis) in 22 patients (88%), pT1 in 2 patients (8%) and pT2 in 1 patient (4%). In
      26 patients (51%) the diagnosis was adenoma. The overall local recurrence rate
      was 9.8% (5/51); the recurrence rate was 7.6% (2/26) for adenomas and 12% (3/25)
      for carcinomas. The median hospital stay was 7 days (range 3-39). There was no
      operative mortality. Giant sessile polypoid lesions localized in the middle and
      upper rectum are best treated with T.E.M., while Parks technique is a good option
      in lower rectal tumours. These techniques, if correctly indicated and well
      performed, offer great advantages in terms of safety and radicality. In our
      experience the operative mortality was nil and the morbidity and recurrence rates
      were low.

PMID- 18709771
TI  - [Surgical treatment of extraperitoneal rectal cancer].
AB  - The aim of the study was to evaluate the results of open surgery with sphincter
      preservation and nerve-sparing total mesorectal excision and a fast-track
      protocol, without a protective stoma in a consecutive series of patients with
      extraperitoneal rectal cancer. From 1998 to 2007, 89 patients with
      extraperitoneal rectal cancer were treated according to a prospective protocol.
      Eight-six patients were submitted to anterior resection with a low or ultra-low
      anastomosis and nerve-sparing total mesorectal excision. Fifty-four patients
      received neoadjuvant therapy. Twenty-eight patients were treated according to a
      fast-track postoperative protocol. Primary protective colostomies were performed
      in 6 cases (6.9%), while a secondary colostomy was necessary in 3 patients
      (3.4%). There was just one postoperative death (1.1%) and major morbidity
      occurred in 12.3%. Seven patients developed anastomotic dehiscence; 3 were
      successfully treated with a secondary colostomy and 4 were treated
      conservatively. 68.4% of the patients treated with the fast-track protocol could
      be discharged on postoperative day 4. 73% of patients were still surviving at a 5
      year follow-up (48 patients). The incidence of local recurrences was 3.1%.
      Anterior resection in the form of open nerve-sparing total mesorectal excision
      with selective use of neoadjuvant therapy can be successfully performed without a
      protective stoma in more than 80% of patients. The fast-track protocol seems to
      increase the quality of the patient's postoperative condition and reduce the
      hospital stay.

PMID- 18709773
TI  - [Familial polyposis coli associated with carcinoma of the uterine cervix].
AB  - Familial polyposis coli is a heterogeneous disease with a broad spectrum of
      clinical manifestations including not only multiple polyposis of the small bowel,
      but also multiple primary tumours, such as carcinoma of the ampulla of Vater,
      subcutaneous tumours, bone tumours, central nervous system tumous and
      gynaecological malignancies. This report is of two brothers with familial
      polyposis, each showing peculiar distinctive features. In one case, polyposis was
      diagnosed during emergency surgery for ileo-colic intussusception. The patient
      later developed a tumour of the uterine cervix. Polyposis coli was identified
      late in the second patient who showed an evolution towards colonic adenocarcinoma
      with multiple hepatic metastases. The possible association of familial polyposis
      and extracolonic malignancies has already been emphasized in the literature. In
      this report we wish to stress the advisability of periodic gynaecological check
      ups in affected patients.

PMID- 18709774
TI  - [Extension of lymphatic resection in the colon cancer].
AB  - It is commonly believed that treatment of colon cancer by surgical resection is a
      standardised approach. A review of the literature, however, shows differences in
      the extent of colon resection among the various different centres. Reported
      results are provided almost entirely by retrospective studies. In the absence of
      prospective randomised studies the ideal extent of colon and lymphatic resection
      in the curative treatment of colon cancer has not yet to be defined. The aim of
      this review was to examine the anatomical, physiological and clinical assumptions
      on which colon resections are habitually based.

PMID- 18709775
TI  - [Surgical treatment of gastric cancer].
AB  - Despite the decrease in incidence observed during the last decades, gastric
      adenocarcinoma remains the fourth most common cancer in the world and the second
      leading cause of cancer-related death. Radical surgical resection is the best
      treatment option, though the role of extended and super-extended lymphadenectomy
      remains debatable. This review examines the different issues related to the
      surgical treatment of early and advanced gastric adenocarcinoma as well as the
      most recent strategies for the treatment and prevention of peritoneal
      carcinomatosis.

PMID- 18709776
TI  - Abdominal compartment syndrome: a situation thet needs to be better known.
AB  - Abdominal compartment syndrome was initially described as a cascade of
      physiopathological events triggered by the increase in intra-abdominal pressure
      induced by a surgical procedure for aneurysm of the abdominal aorta. In practice,
      it is a complication that can arise after various procedures; it has a multi
      organ impact and can lead to exitus. We retrospectively analyzed a total of 9
      patients with abdominal compartment syndrome. In 5 cases onset of the syndrome
      was due to a secondary complication of a vascular procedure (3 mesenteric, 2
      renal). The clinical data characterizing the disease included abdominal
      distension and reduced diuresis. In all cases the finding of increased necrosis
      scores (LDH, CPK) was evident, while the appearance of leukocytosis occurred only
      in 4 (44%). The basic treatment was surgical decompression. In one case we
      obtained an excellent result with medical treatment alone, consisting in steroids
      and PGE1; these were useful in all cases in which an inflammatory bowel component
      played a role. Our experience encourages us to stress the importance of early
      assessment of abdominal hypertension in patients with a potential risk of
      abdominal compartment syndrome. In this phase, appropriate medical and supportive
      treatment could limit the surgical indications or at any rate favour the healing
      process after surgical decompression, the basic treatment indicated for this
      syndrome.

PMID- 18709778
TI  - Multidisciplinary day surgery unit: seven years' experience.
AB  - The autonomous multidisciplinary day surgery unit is the gold standard for day
      surgery procedures. The Authors report their experience with the Pescina Hospital
      autonomous multidisciplinary day surgery unit (Avezzano Heath Authority,
      University of L'Aquila). In total, 4140 patients were enrolled to the day surgery
      setting from 2001 to 2007. Age, gender and ASA of patients, type of disease,
      surgery, anaesthesia and the usual day surgery activity quality indices
      (cancellation and delays of operations, postoperative pain and nausea or
      vomiting, postoperative morbidity, discharge and early readmission) were
      evaluated. 4046 patients underwent day surgery (orthopaedic 29.8%, general
      surgery 26.2%, ophthalmology 21.6%, vascular surgery 19.8%, miscellaneous 2.6%).
      Rates of cancelled and delayed operations were 2.3% and 2.4%, respectively. Local
      anaesthesia was performed in 54.3% of operations. None of the patients reported
      postoperative nausea and vomiting. Severe postoperative pain was present in 10%
      of cases. 77% of patients was discharged within four hours of surgery, and the
      others within six hours. Four patients (0.11%) were readmitted early. The
      postoperative morbidity and mortality rates were 0.49% and 0%, respectively. None
      of the postoperative events correlated with gender, age, ASA, or type of surgery
      and anaesthesia. The multidisciplinary day surgery unit, with dedicated medical
      and nursing staff and suitable organisation such as ours is characterised by
      favourable surgery activity quality indices and good patient outcomes.

PMID- 18709777
TI  - [Quadrantectomy and removal of the sentinel lymph node under local anaesthesia in
      the day hospital setting].
AB  - In recent years, breast carcinoma diagnostics and therapy have evolved very
      considerably, allowing conservative surgery in most cases. These kinds of major
      operations have been greatly simplified since the introduction of the sentinel
      lymph node approach, with the possibility of a day surgery operation under local
      anaesthesia. The aim of this study, after thorough analysis of the axillary lymph
      nodes with ultrasound and cytological examinations, was to assess whether it
      would be possible to distinguish between negative and metastatic lymph nodes and
      whether the operation could be performed under local anaesthesia without
      hospitalisation. From January 2005 to January 2007, 54 breast carcinoma patients
      with negative axillary lymph nodes (after ultrasound examination) had a
      quadrantectomy and sentinel lymph node removal under local anaesthesia together
      with sedation where appropriate. Eight patients who presented micrometastases or
      isolated tumour cells in the sentinel lymph node underwent a subsequent
      lymphadenectomy. Our data show that, thanks to thorough analysis of the axillary
      cavity, it may be possible to use the sentinel lymph node approach with a good
      chance of the patient remaining free of distant metastases and of operating under
      local anaesthesia.

PMID- 18709779
TI  - Tension-free hernioplasty of recurrent inguinal hernia under local anaesthesia: a
      5-year review.
AB  - The aim of this study was to describe the tension-free hernioplasty of recurrent
      inguinal hernia under local anaesthesia via the anterior approach, in order to
      evaluate the feasibility, safety and effectiveness of local anaesthesia and its
      outcome in terms of hernia recurrence and chronic inguinal pain. The effects of
      hernia type, type of anaesthesia, comorbid disease and complications on
      recurrence and chronic inguinal pain were analysed. Fifty-nine procedures were
      performed electively on 56 adult patients. Local anaesthesia was used in all
      patients. In 4 patients (7%) a shift from local to general anaesthesia became
      necessary to conclude the procedure due to intra-operative pain. Three cases (5%)
      with a bilateral inguinal hernia were treated at the same time. Thirty-five (59%)
      recurrences were repaired with the technique proposed by Lichtenstein, 13 cases
      (22%) with the dynamic self-regulating (P.A.D.) system, and 11 cases (19%) with a
      plug repair. After a median follow-up of 96 months there was only 1 recurrence
      (1.6%) and 1 case of chronic inguinal pain (1.6%). We conclude that use of local
      anaesthesia is indicated in recurrent inguinal hernia not only for its
      simplicity, safety and lasting postoperative analgesia, but especially for the
      lack of potentially detrimental cardiovascular effects observed with general
      anaesthesia.

PMID- 18709780
TI  - [Laparoscopic repair of incisional and ventral hernia].
AB  - The application of laparoscopic principles to ventral or incisional hernia repair
      has recently been shown to be a safe and effective alternative to open
      procedures. In this study we analyzed our recent experience with laparoscopic
      incisional-ventral hernia repair. The outcomes of 75 consecutive patients
      (January 2002 to July 2006) who underwent laparoscopic repair for incisional
      ventral hernia were reviewed. Patient's demographics, hernia parameters, and
      intraoperative and postoperative data were collected. Of the 75 patients, 44 were
      females and 31 males. Mean age was 59.1 yrs (range 29-80 yrs). Mean BMI was 25.9
      (range 19.4-36.7). Twenty-one patients had primary ventral hernias while 54
      patients had an incisional hernia. Fifty-three patients had a single defect and
      22 patients multiple defects. In 45 cases the incisional hernia was a primary
      hernia; in 4 cases it was a first recurrence; in 2 cases a 2nd recurrence; and in
      3 cases a 3rd recurrence. The mean defect size was 52,7 cm2 (range 4-432).
      Laparoscopic hernia repair was successfully performed in 71 cases (94.7%). The
      mean mesh size was 211 cm2 (range 63-694). Mean operating time was 101 min (range
      50-220 min). The mean hospital stay was 4.7 days. The postoperative morbidity
      rate was 14%. After a mean follow-up of 24.6 months (range 7-56) the recurrence
      rate was 7% (5/71). Laparoscopic repair of incisional-ventral hernias seems to be
      safe and effective. Medium-term outcomes were promising with a relatively low
      rate of conversion to open surgery, a low complication rate and a low risk of
      recurrence.

PMID- 18709781
TI  - [Ascending thrombophlebitis of the greater saphenous vein: proposal of a new
      morphological classification].
AB  - Superficial thrombophlebitis has been considered a self-limiting, benign disease
      without any significant incidence of morbidity or mortality. Thrombosis of the
      saphenous vein close to the deep venous system is a potentially dangerous
      clinical situation that may progress to deep venous thrombosis and pulmonary
      embolism. We retrospectively analysed 32 patients with ascending thrombophlebitis
      of the proximal greater saphenous vein who underwent emergency surgical ligation
      of the saphenofemoral junction. In 3 patients (9%) a femoral thrombectomy was
      performed because we observed an extension of the thrombus to the femoral vein
      intraoperatively. The postoperative morbidity and mortality rates were 0%, while
      the incidence of postoperative pulmonary embolism was 3%. In our opinion,
      emergency surgical ligation of the saphenofemoral junction is a valid alternative
      to medical treatment for thrombophlebitis of the proximal greater saphenous vein.
      At the moment no randomised comparison of the efficacy of different treatments
      tested in a large series is available. According to our experience and on the
      basis of the anatomical and haemodynamic studies conducted by Bisacci and
      Genovese, we have identified 2 different types of thrombophlebitis of the
      proximal greater saphenous vein, which require different treatments. In type 1,
      the thrombus does not reach the pre-ostial valve; simple ligation of the
      saphenofemoral junction after its opening is necessary. In type 2, the thrombus
      goes beyond the pre-ostial valve; thrombectomy, saphenofemoral disconnection and
      postoperative anticoagulation are mandatory.

PMID- 18709782
TI  - [Radiofrequency Milligan-Morgan haemorrhoidectomy in the outpatient setting].
AB  - The demand for shorter admissions and quicker recoveries prompted us to adopt a
      new approach, favouring day surgery as the preferred organisational modality.
      Since 2004, 312 Milligan-Morgan haemorrhoidectomies have been performed at our
      department of surgery. The operations were performed at our proctological
      outpatient unit by means of LigasureTM with immediate discharge. In our study we
      observed postoperative bleeding in 3 cases (0.96%), while 4 patients (1.28%)
      required an ordinary admission. There were no cases of acute urinary retention in
      our experience. Operating time is about 12-16 minutes; and recovery time around
      60-70 minutes. Over the period 1992-2003, 978 Milligan-Morgan haemorrhoidectomies
      were performed at our department of surgery using diathermy. Historical
      comparison of the results of the two groups shows a reduction in complications,
      operating times and recovery times. On the basis of our experience,
      radiofrequency ablation causes less postoperative pain and makes for shorter
      recovery times compared with diathermy, because of its lower tissue damage. The
      aim of the present study was to verify the safety and effectiveness of day
      surgery haemorroidectomy in selected cases.

PMID- 18709783
TI  - Treatment of pilonidal sinus with primary closure. A twenty-year experience.
AB  - From 1985 to 2004, 229 patients (171 M, 58 F) aged from 16 to 35 years, affected
      by pilonidal sinus were treated by complete excision of the sinus and primary
      closure. Primary healing was achieved in 208 patients (91%) in an average time of
      11.9 days. Secondary healing was achieved in 21 patients (9%) in 16-19 days. The
      mean postoperative hospital stay was 1.9 days and the average time off work 16
      days. Recurrent pilonidal sinus was observed in 10 patients with a mean follow-up
      of 18 months (range: 12-24). On the basis of their experience, the authors
      conclude that complete excision of the pilonidal sinus with primary closure
      yields good results in terms of healing, morbidity, early return to work and
      recurrence rate and can be considered the treatment of choice for pilonidal
      sinus.

PMID- 18709784
TI  - "Open" abdominal surgery for large incisional hernias. Proposal of a personal
      technique.
AB  - Incisional hernia is still a serious complication of abdominal surgery because of
      its substantial incidence. We have to reduce the rate of complications and, if
      possible, correct the aesthetic defect due to the pathology itself. The
      complications are directly related to different factors (surgeon, technique, type
      of mesh used, patients with associated pathologies etc.). We propose an "open"
      technique to repair incisional hernias using a polypropylene mesh, sutured in a
      space created between two peritoneal sheaths, located in an intraparietal site
      (retromuscular and extraperitoneal), with suturing of the subcutaneous tissue,
      and without a subcutaneous drainage. We studied 26 patients, including obese
      subjects, from 2003 to 2006. The follow-up was 24 months. Good short- and long
      term results were observed. We had two cases of seroma, treated conservatively.
      No prosthetic infections were reported, no recurrences were observed and a good
      final aesthetic result was achieved. In view of the fact that incisional hernia
      admittedly presents different problems from case to case, surgical experience and
      an imaginative surgical approach will always be useful in relation to the rigid
      technical times involved.

PMID- 18709785
TI  - Laparoscopic wedge resection for gastrointestinal stromal tumour of the duodenum.
AB  - We report the case of a 40-year-old male patient who presented with melaena and
      acute anaemia. Endoscopic ultrasound examination revealed a lesion with a central
      depression measuring 2.5 cm, arising from the lateral wall of the second portion
      of the duodenum. Because of this rare location, a very invasive procedure
      (duodenopancreatectomy) might have been required for tumour resection. We avoided
      this operation and implemented an alternative solution. A laparoscopic wedge
      resection of the duodenal tumour was successfully completed. Operating time was
      200 min and blood loss 50 ml. The patient was discharged on postoperative day 3,
      after an uneventful postoperative recovery. Histopathologically, the tumour was
      diagnosed as a low-risk gastrointestinal stromal tumour. Despite the fact that
      laparoscopic surgery requires more complex technique than open surgery and the
      acquisition of advanced laparoscopic skills depending on prior laparoscopic
      experience, laparoscopic wedge resection should be considered as a valid
      treatment for duodenal stromal tumour.

PMID- 18709786
TI  - [Synchronous gastric and oesophageal cancer: a case report].
AB  - We describe the case of a male patient, aged 50, affected by an undifferentiated
      cancer of the gastric stump of a Billroth II gastric resection associated with a
      well-differentiated squamous-cell cancer of the oesophagus. The patient was
      submitted to gastrectomy and removal of the oesophagus together with
      reconstruction trough colon interposition. The association of the two synchronous
      neoplasms of the stomach and oesophagus is a very uncommon event, as the evidence
      in the medical literature demonstrates. Nevertheless, for the purposes of
      achieving in the right surgical planning, it is important to take this
      possibility into consideration in the preoperative management of oesophageal
      cancer, through the study of the organs which could be used to reconstruct the
      transit (stomach, colon). The association with a gastric neoplasm implies the use
      of the other organs (colon, ileum). However, for a number of selected cases of
      association with early gastric cancer, Japanese authors have suggested using the
      stomach in place of the oesophagus.

PMID- 18709787
TI  - Surgical management of hepatic artery aneurysm: a case report.
AB  - Hepatic artery aneurysms are uncommon and account for 20% of splanchnic artery
      aneurysms. The real incidence is unknown, but it is estimated to be 0.4% or less.
      Therapeutic procedures can be performed either surgically or as endovascular
      treatment. We report a case of a 77-year old man who was referred to our
      institute for an asymptomatic atherosclerotic hepatic artery aneurysm, measuring
      4.5 cm in diameter, without evidence of dissection or rupture, involving the
      common and the proper hepatic artery. Resection of the aneurysm was performed,
      and the gastroduodenal artery was ligated. Reconstruction consisted in placement
      of an end-to-end prosthetic graft between the origin of the common hepatic artery
      and the distal third of the proper hepatic artery. An intraoperative arteriogram
      revealed a complete interruption of flow in the left hepatic artery.
      Intraoperatively, dissection of the left hepatic artery was revealed. Therefore
      the left hepatic artery was ligated and a new end-to-end prosthetic graft was
      performed between the origin of the common hepatic artery and the right hepatic
      artery. The postoperative course was complicated by respiratory failure requiring
      ventilator-assisted breathing. The patient was subsequently weaned from the
      ventilator and was discharged to our ward 4 days after surgery. No long-term
      hepatic or pancreatic complications were detected.

PMID- 18709788
TI  - Jejunal adenocarcinoma: still an elusive diagnosis. Case report and review of the
      literature.
AB  - Tumours arising in the small bowel are rare, accounting for less then 2% of all
      gastrointestinal neoplasms. Adenocarcinoma accounts for 40% of small bowel
      malignancies. They are rarely considered as a differential diagnosis, and their
      discovery is usually greeted with surprise. We present a case in which aspecific
      symptoms of this neoplasm, non-informative instrumental examinations and a
      coexisting hiatal hernia led to the misdiagnosis of reflux disease until a
      complication such as abdominal occlusion occurred. To the best of our knowledge
      this is the second case in the literature in which a jejunal adenocarcinoma
      mimicked a gastro-oesophageal reflux disease and delayed the correct diagnosis.

PMID- 18709789
TI  - Adrenal epithelioid angiosarcoma: a case report.
AB  - We report what to the best of our knowledge is the first case of primary
      angiosarcoma of the adrenal gland. A 49-year-old woman, with blunt abdominal
      trauma, was admitted to our department. Computed tomography revealed a suspected
      rupture of a liver neoplasm and surgical treatment was performed. At laparotomy
      there was no evidence of liver tumour but a large mass was found in the right
      adrenal gland. The mass was removed along with the entire periadrenal fat tissue
      and locoregional lymph nodes. Microscopically, we found diffuse neoangiogenesis
      with large, hyperchromatic cells. This cellular proliferation, together with the
      widespread necrosis, distorted the normal appearance of the adrenal gland. No
      adjuvant therapy was administered. Six months and 1 year later thoracic-
      abdominal computed tomography and positron emission tomography were performed,
      and no signs of local recurrence or metastases were observed.

PMID- 18709790
TI  - Isolated polyarteritis nodosa of the large bowel: a case report.
AB  - Polyarteritis nodosa is a form of vasculitis that affects several organs.
      Gastrointestinal involvement is frequent, but cases in which the gastrointestinal
      tract is the only site of disease are rare. In this paper we report a case of a
      70-year-old patient with polyarteritis nodosa restricted to the large intestine,
      who underwent a total colectomy. The patient had no other signs of chronic
      vasculitis and for this reason surgical treatment resolved the clinical symptoms.

PMID- 18709791
TI  - Paratesticular leiomyosarcoma: a case report.
AB  - Leiomyosarcomas of the spermatic cord are extremely rare. This article reviews
      the pathophysiology of spermatic cord leiomyosarcomas and the reasons for
      recurrence, and discusses the management options. Radical inguinal orchiectomy
      and high ligation of the cord is the standard primary surgical procedure.

PMID- 18709792
TI  - [Case report of a cervical thoracic duct cyst].
AB  - After a number of anatomical considerations regarding the thoracic duct and the
      diseases that may affect it, the authors report that, in the literature, such
      cystic lesions of an iatrogenic nature are extremely rare in the cervical area.
      After discussing the diagnostic methods for a correct preoperative diagnosis,
      they address the surgical technique they used for removal of the lesion.

PMID- 18709793
TI  - A rare case of left diaphragmatic agenesis in an elderly patient.
AB  - A 71-year-old man affected by left hemidiaphragmatic agenesis developed late
      severe constipation and occasional episodes of bowel obstruction. At left
      subcostal laparotomy, the stomach, transverse colon, splenic flexure, and spleen
      were located in the left hemithorax. Repair was performed with a 2-mm-thick
      expanded polytetrafluoroethylene (Gore-Tex) patch secured in place
      circumferentially as a new diaphragmatic dome. No early major complications and
      no recurrence at 34 months' follow-up were observed. To the best of our
      knowledge, this is the oldest treated patient with a true hemidiaphragmatic
      agenesis and is the eighth case reported in the literature. The use of the ePTFE
      soft tissue patch, thanks to its strength and pliability, affords good anatomical
      and functional repair.

PMID- 18709794
TI  - Volvulus due to a giant sigmoid diverticulum: a rare cause of intestinal
      occlusion.
AB  - The case of a giant sigmoid diverticulum complicated by a volvulus of the bowel
      is reported. After an exhaustive literature review, the Authors analyse the
      aetiopathogenetic, physiopathological and clinical aspects of this rare
      condition, considering its diagnostic and therapeutic implications. The Authors
      describe surgical problems and therapeutic management, pointing out that without
      an accurate study by radiological imaging, it is very difficult to diagnose the
      condition, particularly when no specific symptoms have been observed.

PMID- 18709795
TI  - Bring back lying in.

PMID- 18709796
TI  - The cost of not being nice.

PMID- 18709797
TI  - Hyperemesis gravidarum: how midwives can help.

PMID- 18709798
TI  - Just a normal disabled mum.

PMID- 18709799
TI  - Informed consent and the birth plan.

PMID- 18709800
TI  - Safety in maternity services: women's perspectives.

PMID- 18709801
TI  - Rebalancing obstetric and midwifery thinking.

PMID- 18709802
TI  - Good on ya, Trish!

PMID- 18709803
TI  - We have work to do.

PMID- 18709804
TI  - Midwives: the key to a healthy future.

PMID- 18709805
TI  - Sharing sleep with breastfed babies (2). Research suggests sweet dreams result.

PMID- 18709806
TI  - Students at large (4). Going Dutch: midwifery in the Netherlands.

PMID- 18709807
TI  - Folic acid: the plot thickens.

PMID- 18709808
TI  - Research unwrapped. Breastfeeding method and infant weight gain.

PMID- 18709809
TI  - Bearing the load for women.

PMID- 18709810
TI  - [Antioxidant power and cellular damage in prostate cancer].
AB  - OBJECTIVES: To determine and compare the antioxidant power, cellular damage by
      lipidic peroxidation, and membrane damage in normal patients and patients with
      prostate cancer, so determining the antitumoral capacity. METHODS: The study
      population included 19 patients with elevated total PSA, greater than 4 ng/ml,
      with a minimum of 10 ultrasound guided transrectal biopsies, and 10 normal
      subjects as control group. In all cases, medical history, rectal digital
      examination, PSA determination and routine analyses were performed in addition to
      spectrophotometric tests to measure the antioxidant power. Membrane damage was
      measured by determination of malonyldialdehyde (MDA) and cellular damage by
      glutathione peroxidase. RESULTS: From a total of 19 cases: 6 (31.5%) presented
      prostate cancer (4 Gleason 7; 1 Gleason 6 and 1 Gleason 8); 8 presented
      histological benign prostatic hyperplasia with a component of chronic
      prostatitis; 3 patients prostatic hyperplasia and glandular atrophy; and 2 cases
      isolated benign prostatic hyperplasia. All 10 control patients presented values
      within normal range in all determinations, whereas study patients showed
      antioxidant power < 1.3 mmol/l in 13 cases; higher than 1.77 mmol/l in 4 and
      normal values in 2. MDA was elevated in 15 patients and normal in 4, all of them
      without histological chronic prostatitis. Four of the patients with prostate
      cancer presented a diminished antioxidant power below 0.90, with a relationship
      with glandular architecture, because those with Gleason 8 and 7 did not exceed
      0.58 mmol/l. Two patients with prostate cancer with a lower Gleason score
      presented normal minimal values. CONCLUSIONS: Patients with prostate cancer or
      reactive processes, such as chronic prostatitis or atrophic prostatitis, present
      a decreased antioxidant power and an increase of lipidic peroxidation.

PMID- 18709811
TI  - [Hematuria of papillary or medullar origin: a difficult diagnosis entity].
AB  - OBJECTIVES: Renal haemangiomas of renal papillary or medullar origin are a
      difficult diagnosis entity, being one of the most frequent processes of chronic
      episodes of hematuria, secondary to benign disease, mainly in young patients. The
      objective of this paper is to show the difficulty of this diagnosis and the need
      to suspect it in cases with clinical history similar to the ones described in
      these cases. METHODS: We report 4 cases of spontaneous hematuria of renal origin,
      with clinical presentation as renal colic, from the historical case series of the
      Fundacion Jimenez Diaz-Capio, the last two from the years 2005-6. We present the
      diagnostic and therapeutic methodology employed, including angio-CT and flexible
      ureterorenoscopy (URS) as well as various treatment options. RESULTS: Hematuria
      was identified as "essential" when any relation with tumor or lithiasic
      pathologies was ruled out, and of renal origin when the source was clearly
      pointed. We interpreted it was related to angiomas or microangiomas of papillary
      or medullar origin. In one case, the vascular malformation was interpreted as an
      arterial venous fistula (AVF) at that level. Hematuria stopped spontaneously in
      two cases after exploratory URS. The eldest historical case required surgical
      expiration of the caliceal structures. CONCLUSION: Years ago, following the
      professional development of Urology as speciality, conventional surgery was
      carried out in all these cases, of very difficult diagnosis, with a very small
      number of cases undergoing a conservative approach based on the examination of
      renal cavities trying to observe and find the bleeding point. Most cases
      underwent complete or partial nephrectomy. Currently, the possibility of
      exploration of all renal cavities with the flexible ureterorenoscope enables a
      better diagnosis of the lesions and a more conservative treatment. The ultimate
      diagnosis of renal papillary angioma is the pathologic diagnosis, without
      pathognomonic data in the imaging tests. This pathology is thought of at the end
      of the diagnostic workup, and when the papillary area is identified as the source
      of bleeding. The historical case series, with the pathologic findings from
      nephrectomy specimens, permits us to point out this entity as papillary angioma,
      in patients with similar clinical presentation.

PMID- 18709812
TI  - [Ultrasound guided transrectal prostatic biopsy and pain. Prospective randomized
      study comparing lubricant gel, lidocaine gel, and anesthetic blockage of the
      neurovascular bundles with 1% lidocaine].
AB  - OBJECTIVES: To quantify anxiety and immediate and late pain, efficacy of the
      common analgesic methods, and complications. METHODS: 117 patients were
      randomized to three groups: 1 (39): lubricant gel; 2 (38): intrarectal lidocaine
      gel; 3 (40): anesthetic blockage with 1% lidocaine. Complications and immediate
      and late pain were collected, these latter with a visual analogic scale. RESULTS:
      70% of the patients were not much anxious. We did not find significant
      differences between the analgesia achieved in group 1 (4.37 +/- 2.41) and group 2
      (4.22 +/- 2.46), but we found with group 3 (1.88 +/- 2.03). Mean pain score the
      afternoon after biopsy was lower in group 3 (2.08 +/- 2.28) than in groups 1 and
      2 (4.06 +/- 2.80 and 2.42 +/- 2.03), without statistical significance. The
      patients did not show a difference in pain during the pass of the transrectal
      transducer, varying between 2.34 for group 3 and 3.38 for group 2. Grouped by
      sphincter tone we find differences (low 2.71 +/- 2.76, medium 3.23 +/- 2.38, high
      4.99 +/- 2.22). Patients feeling very nervous before the test had a pain score of
      4.98 +/- 2.57, significantly greater than the pain of those not feeling nervous
      (2.59 +/- 2.21). We did not find differences in complications between the three
      groups. CONCLUSIONS: The use of intrarectal lidocaine gel did not demonstrated
      being more effective in pain control in our series than the use of lubricant gel,
      but lidocaine injected into the apex and seminal vesicles was. Sphincter tone and
      pretest anxiety are the most determinants factors for pain.

PMID- 18709813
TI  - [Practical guideline for the management of adverse events associated with BCG
      installations].
AB  - OBJECTIVES: Morbidity secondary to intravesical Bacillus Calmette-Guerin (BCG)
      may present both locally and systemically. Most patients suffer a self-limited
      irritative voiding syndrome. Often, there are not unified criteria for the
      management of BCG side effects. After treating more than 500 patients with BCG we
      developed a practical guideline for the management of its morbidity. We present
      clearly and schematically the practice guideline we follow in our Center when the
      patient presents symptoms and morbidity secondary to BCG intravesical
      installations. METHODS: We analyze and describe, following the literature and our
      own experience, the management of adverse events experienced by patients treated
      with intravesical BCG, since the initial implementation of the protocol for its
      indication in patients with high risk non-muscle invasive bladder tumors and/or
      CIS. RESULTS: Irritative voiding symptoms are among the most frequent symptoms,
      generally self-limited; but if they persist (> 48 hours) will have the urologist
      treat them depending on intensity and duration. Macroscopic hematuria is not
      unfrequent and diminishes with an expectant approach and water intake. But, it
      may also be a urinary tract infection or residual tumor. A febrile syndrome, if
      present, is usually self-limited to the first 24-48 hours and below 38.5 degrees
      C without general status affectation. In cases of persistence and/or sepsis,
      tuberculostatic treatment and/or corticoids should be started. Other clinical
      pictures may appear, such as orchyoepididymitis, arthritis, etc. CONCLUSIONS:
      Proper diagnosis and treatment of adverse events after BCG therapy are basic to
      allow intravesical immunotherapy be properly prescribed and managed by
      urologists, enabling a proper treatment of patients and avoiding the possibility
      of more severe complications.

PMID- 18709814
TI  - [The treatment of female stress urinary incontinence (SUI) using fascia lata in a
      rural hospital].
AB  - OBJECTIVES: Pubovaginal sling has been the treatment of choice for female SUI
      over the last two years. Those made with autologous materials have demonstrated a
      lower rate of complications. We present our experience using autologous fascia
      lata. METHODS: Between May 2005 and July 2006 we performed 10 procedures through
      a suprapubic approach. In eight cases they were ascended to the retropubic space
      using needles, and in 2 cases we employed the vaginal tunneler (Tyco). In the 8
      initial cases both sling branches were anchored to the Cooper's ligament. In the
      remainder two cases they were anchored to the fascia of the obliquus externus
      muscle. RESULTS: Mean age was 57.7 years; mean follow-up time was 14.8 months (6
      20). In 6 cases cystocele was simultaneously corrected. Hospital stay was 72
      hours. In two cases, section of the autologous sling was required due to
      excessive correction. Four patients keep using pads; nevertheless, all 10
      patients refer no SUI. Post-operative urine culture was positive in four
      patients, with negative controls. One case presented vaginal candidiasis.
      CONCLUSIONS: Autologous fascia lata pubovaginal sling is an effective low cost
      treatment, with a low complication rate.

PMID- 18709815
TI  - [Changes in detrusor contractility in bladder hyperreflexia].
AB  - OBJECTIVES: Classically, it was understood detrusor contractility was affected in
      bladder areflexia but not in hyperreflexia. We aim to demonstrate that there is
      some detrusor contractility affectation in bladder hyperreflexias, although it
      may seem paradoxical at first sight. METHODS: Neuro-urologic study was performed
      in a series of 68 consecutive patients with bladder hyperreflexia (neurogenic
      detrusor hyperactivity), referred to the unit of functional urology for
      urodynamic evaluation. All patients underwent clinical history, post void
      residual determination, cystomanometry, voiding pressure-flow test,
      videourodynamics and selective EMG of the periurethral sphincter. Detrusor
      contractile potency was measured with W 80-20. Terminology follows the ICS
      standard. Data processing was performed using the statistical software SPSS 12.0.
      RESULTS: This series includes 14 males (58.8%) and 28 females (41.2%), of all
      ages (adults more frequent). 88.2% of the cases had acquired neurological
      diseases (trauma 30.9%; medical 33.8%; degenerative 35.3%), and 11.8% congenital
      neurological diseases (myelodysplasia). Most frequent type of neurological lesion
      was detrusor-sphincter dyssynergia: 59 cases (79.4%); 22 patients (32.4%) had
      undergone previous treatment of their vesicourethral dysfunction. The amplitude
      of detrusor involuntary contractions was wider in detrusor-bladder neck
      dyssynergia. Detrusor isotonic contractility (W 80-20) was significantly
      affected, mainly in neurological lesions of traumatic nature and less in
      degenerative lesions (p = 0.01). CONCLUSIONS: We demonstrated that bladder
      contractility is affected in bladder hyperreflexias (neurogenic detrusor
      hyperactivity), more important in traumatic lesions without relationship with the
      type of neurological associated lesion, which could be related to a bladder
      structural change, or with a change in the central neurological tracts (without
      requirement of presence of dyssynergia).

PMID- 18709816
TI  - [Transperitoneal laparoscopic adrenalectomy: results after 70 procedures].
AB  - OBJECTIVES: To present our surgical experience in laparoscopic adrenalectomy
      after 70 procedures, comparing our results with the published series and
      analyzing the learning curve. METHODS: Between June 1997 and December 2007 we
      performed 87 adrenalectomies (70 transperitoneal laparoscopy, 1
      retroperitoneoscopy and 16 open surgery); 60% were female. Mean age was 54 years
      15-80); 35 were left adrenalectomies, 33 right and one bilateral. Mean mass size
      was 3,7 cm (1-10). All patients were assessed regarding the following variables:
      preoperative diagnosis, histopathology, operative time, blood loss,
      complications, conversion to open surgery and hospital stay. We compared the
      results of the first 40 surgical procedures (Group 1) and the last 30 (Group 2).
      We also compared our re-sults with published series. Mean time follow-up was 12
      months (2-60). RESULTS: The most frequent preoperative diagnoses were: active
      suprarenal mass (50%), incidentaloma (20%), pheochromocytoma (20%).
      Histopathology confirmed 60% adenomas, 14% pheochromocytomas and 11% cortical
      nodular hyperplasia. Mean operative time was 161 minutes (60-300). Average blood
      loss (hematocrit) was 5.2 (1-10). Conversion and complication rate were 8.5 and
      7%, respectively. Mean hospital stay was 4 days (2-30). In group 2, only
      reduction on mean operative time (120 min) and hospital stay (3 days) was
      statistically significant. CONCLUSIONS: Transperitoneal laparoscopic
      adrenalectomy is a feasible and safe procedure in urological groups with previous
      laparoscopic experience. Our results are similar to the published series and
      confirm the efficacy, safety and reproducibility of this technique.

PMID- 18709817
TI  - [Extracorporeal tumorectomy and autotransplantation in a patient with a single
      kidney and a multicentric clear cell carcinoma].
AB  - OBJECTIVE: To demonstrate that "bench surgery" and autotransplantation are still
      alternatives in the treatment of complex renal cancer cases. METHODS: 58 y/o
      female with history of radical nephrectomy due to renal cancer who asked for
      medical attention because of back pain. Renal masses were found during her
      evaluation and she was referred to our service. RESULTS: Lumbar incision was the
      preferred approach. After removal, the kidney was irrigated with EuroCollins
      solution and bench surgery was performed. Cold ischemia time was 63 minutes. The
      kidney was transplanted into the right pelvic region. Diuresis was immediately
      achieved after vascular anastomosis. Lich-Gregoir ureteral implant was carried
      out. During the first 48 hrs no complication was reported, urine output was about
      80 cc/hour. She eventually developed renal failure and after 6 sessions of
      hemodialysis recovered to void in the previous volume range. She had a urinary
      leak that was resolved with CFT-guided percutaneus drainage. Twelve months after
      the procedure, she has no complaints; serum creatinine is 1.6 mg/dl and CT scan
      shows no evidence of recurrences. CONCLUSIONS: Bench surgery is still a
      therapeutic alternative for the treatment of complex renal cancer cases in order
      to avoid dialysis.

PMID- 18709818
TI  - [Urinoma secondary to ureteral iatrogenic lesion].
AB  - OBJECTIVES: We present one case of urinoma after gynecologic surgery and the
      surgical repair. METHODS: 46-year-old woman referred for urologic consultation
      for flank pain after hysterectomy. RESULTS: CT scan showed the existence of an
      urinoma with the ureter included in the radiological lesion. CONCLUSION: Early
      treatment after diagnosis with end-to-end anastomosis solved the problem.

PMID- 18709819
TI  - [Coexistence of two germinal cell tumors, seminomatous and nonseminomatous, with
      an uncommon clinical presentation].
AB  - OBJECTIVES: The existence of non seminomatous mixed germ cell tumors of the
      testis is a frequent event in urologic oncology. Nevertheless, the presence of
      both components, seminomatous and non seminomatous, in a germ cell tumor is
      unusual. METHODS: We present a case of pure classic seminoma of the testis with a
      lymph node metastasis of pure embryonal carcinoma, with confirmatory
      immuohistochemical study and clinical outcome of the patient. RESULTS: A 34-year
      old man presented with 3 cm supraclavicular tumor. CT scan also revealed multiple
      metastases in lymph nodes, liver, kidney and left adrenal gland. Tumor markers
      were negative and the biopsy performed discovered a lymph node metastasis of
      embryonal carcinoma of probable testicular origin. Ultrasound revealed a 6 mm
      hypoechoic nodule in the right testis. Orchyectomy was performed and pathologic
      analysis demonstrated a tumor, 1 cm of diameter, histopathologically compatible
      with classical seminoma with pagetoid extension to rete testis. Albuginea and
      spermatic cord did not present neoplastic involvement. Currently the patient is
      being treated with chemotherapy. CONCLUSION: The interest of the case is to
      remark an unusual aggressive clinical presentation as well as to perform a
      bibliographic review with emphasis in the theories regarding heterogeneous
      differentiation and spontaneous regression of germ cell tumors of the testis.

PMID- 18709820
TI  - [Intrathoracic ectopic kidney in an adult: case report and bibliographic review].
AB  - OBJECTIVE: We report the case of a 61-year-old male with the incidental diagnosis
      of intrathoracic renal ectopia during the workup study for a possible lung mass.
      METHODS: We performed a bibliographic review on the incidence, origin, clinical
      presentation and diagnosis of this type of renal ectopia. RESULTS: Chest x-ray
      showed a left posterior mediastinum mass. Bronchoscopy was performed showing
      signs of extrinsic compression with absence of neoplastic cells. CT scan revealed
      a left intrathoracic ectopic kidney with diaphragmatic hernia. CONCLUSIONS:
      Intrathoracic renal ectopia is a very unfrequent finding, often asymptomatic,
      frequently an incidental diagnosis that does not require treatment.

PMID- 18709821
TI  - [Squamous cell carcinoma in a duplicated renal pelvis after percutaneous
      nephrolithotomy].
AB  - OBJECTIVE: To describe the clinical case of a patient presenting a squamous cell
      carcinoma in a duplicated renal pelvis, after percutaneous nephrolithotomy.
      METHODS/RESULTS: 60-year-old male patient who was diagnosed of a squamous cell
      carcinoma of the renal pelvis in the pathological study of a lower pole
      nephrectomy after percutaneous nephrolithotomy for staghorn calculi in the left
      lower pole renal moiety. The patient suffered a bladder recurrence one year and a
      half later. A radical cystoprostatectomy was performed, but the patient died in a
      few months due to metastasis. CONCLUSIONS: Squamous cell carcinoma of the renal
      pelvis is a rare tumor with poor prognosis, associated with stone disease and
      chronic infection. Taking biopsies from suspicious lesions during percutaneous
      nephrolithotomy may help early diagnosis and improve survival.

PMID- 18709822
TI  - [Prostatic utricle ductal carcinoma. Case report and bibliographic review].
AB  - OBJECTIVE: A case of ductal carcinoma of the prostatic utricle is described,
      previously known as endometrial carcinoma, and literature is reviewed. METHODS:
      75-years-old patient who consults for lower urinary tract obstructive symptoms,
      with a PSA of 8.1 ng/ml., without more symptoms. Digital rectal examination and
      ultrasound showed a small and stony prostate. Deobstructive transurethral
      resection of the prostate was performed and the biopsy revealed ductal carcinoma
      of the utricle. RESULTS: Nine years after diagnosis signs of dissemination are
      not present. CONCLUSIONS: As incidental finding in the biopsy, ductal carcinoma
      of the utricle is a rare tumor, the incidence of which among all prostatic
      carcinomas has been cited as 0.2-0.8%. We report a review about this topic for
      improving its knowledge. Symptoms, pathological findings and treatment of this
      carcinoma have been reviewed.

PMID- 18709823
TI  - [Bladder lithiasis secondary to intrauterine device migration. Case report].
AB  - OBJECTIVE: To report one clinical case of bladder lithiasis secondary to the
      migration of an intrauterine device, its symptoms, diagnostic tests employed and
      treatment. METHODS/RESULTS: 30-year-old female patient who presented lower
      urinary tract irritative symptoms. One year before she underwent insertion of an
      intrauterine device (copper T) after endometrial curettage for pregnancy
      interruption. She received treatment for infection cystitis over two years, with
      various antibiotic cycles. The persistence of symptoms led her to the urology
      clinics, and a 5 x 3 cm intravesical lithiasis with a copper T inside was
      detected by ultrasound and pelvic anterior-posterior x-ray Suprapubic
      cystolithotomy was performed with a good outcome and disappearance of the
      symptoms. CONCLUSIONS: The migration of an intrauterine device to the bladder is
      an unfrequent cause of bladder lithiasis secondary to foreign body. Nevertheless,
      we must consider this possibility in front of chronic lower urinary tract
      irritative symptoms in every female using this birth control method.

PMID- 18709824
TI  - [Testicular epidermoid cyst].
AB  - OBJECTIVE: Testicular epidermoid cysts are rare and can be clinically misleading
      with other testicular neoplasms. We describe a case of epidermal cyst of the
      testis, with the aim to contribute to the clinicopathological knowledge of this
      entity. METHODS: A 24-year-old caucasian man presented with a self-detected right
      testicular mass. Ultrasound features were consistent with solid tumor. He
      underwent an inguinal radical orchyectomy. RESULTS: An intraparenchymal cyst
      measuring 1,4 cm was observed, covered by epidermal epithelium with no other skin
      components. Adnexal testicular pulp was normal. CONCLUSIONS: When a preoperative
      diagnosis is made, a conservative treatment is recommendable, including frozen
      sections analysis of the cyst and adjacent testicular parenchyma to rule out a
      coexistent intratubular germ cell neoplasia.

PMID- 18709825
TI  - [Renal infarction in the evaluation of lumbar pain].
AB  - OBJECTIVE: We report the case of a young patient without known cardiovascular
      risk factors, complaining of lumbar colic pain due to renal infarction. METHODS:
      Differential diagnosis of lumbar colic pain must include some rare events. We
      performed a review of the current knowledge on the topic. RESULTS/CONCLUSION: The
      increasing difficulty in the diagnosis of these pathology lies on its clinical
      suspect, which can be clear when having cardiovascular risk factors. Its
      diagnosis, on a rare scenario, needs leucocytosis and LDH rising as suspicious
      indicators. Computed tomography, MRI, radionuclids and arteriography may confirm
      diagnosis. Treatment is based on thrombolytic therapy, anticoagulants and
      ontiagregants.

PMID- 18709826
TI  - Lung metastases of low grade phyllodes tumor of the prostate: histopathologic
      confirmation.
AB  - OBJECTIVE: Phyllodes tumor of the prostate is a rare neoplasm. We report the
      clinical, histopathological, and immunohistochemical features of a low grade
      phyllodes tumor of the prostate with lung metastases. METHODS: A 68-year-old man
      presented acute urinary obstruction. Suprapubic prostatectomy was performed, and
      one month later he developed acute urinary obstruction, shortness of breath and
      cough. RESULTS: Microscopically, the prostatic tumor showed elongated ducts and
      cellular stroma. Lung biopsy was composed of stromal cells with enlarged,
      hyperchromatic nuclei. CONCLUSION: This case represents a typical low grade
      prostatic phyllodes tumor to lung. Grading of these neoplasm is not always of
      value to predict patient prognosis.

PMID- 18709827
TI  - ["Regional and national elections are important for the development of the
      Order". Interview by Sylvie Warner].

PMID- 18709830
TI  - [Growth of health care needs and management of the influx of patients in critical
      care].

PMID- 18709829
TI  - [Influence of the environment on human relationships in critical care].

PMID- 18709831
TI  - [The nurse at the center of health care delivery].

PMID- 18709832
TI  - [The specifics of relationship management in critical care].

PMID- 18709833
TI  - [Management of families and relatives in critical care].

PMID- 18709834
TI  - [Coping with death in critical care, the ending of therapy].

PMID- 18709835
TI  - [The nursing staff, an important actor in care relationships].

PMID- 18709836
TI  - [The day I woke up in critical care....].

PMID- 18709837
TI  - [Rediscovering the practice of nursing in patient education. Interview by Sylvie
      Warnet].

PMID- 18709838
TI  - [The nurse and medical prescriptions].

PMID- 18709839
TI  - [Improving pain management in the elderly patient].

PMID- 18709840
TI  - [Between euthanasia and unreasonable continuation of therapy, where is the room
      for nursing thought?].

PMID- 18709841
TI  - [Personnel staffing with nursing students, a shared responsibility].

PMID- 18709843
TI  - [Helping relationships, a therapeutic project].

PMID- 18709842
TI  - [Concrete case in orthopedic rehabilitation].

PMID- 18709844
TI  - [Valerie de Gasparin (1813-1894)].

PMID- 18709845
TI  - [Natalizumab].

PMID- 18709846
TI  - [The changes of Fourier transform infrared spectroscopy in rat's brain].
AB  - OBJECTIVE: To apply Fourier transform infrared (FTIR) spectroscopy to study the
      process of postmortem degradation of the rat brain and to provide a new way for
      the estimation of postmortem interval (PMI). METHODS: The rats were sacrificed by
      cervical dislocation and the bodies were kept in a controlled environmental
      chamber set at (30 +/- 2) degrees C. To measure the content of the chemical
      groups in postmortem rat brains at the different time points from 0 to 36 h using
      the FTIR spectrograph. RESULTS: With prolongation of PMI, the peak position of
      main absorbance bands in the FTIR spectra showed no significant changes, while
      the peak levels showed dramatic changes: (1) The relative peak intensity of 1080
      cm(-1), 1238 cm(-1) (I1080/I1398, I1238/I1398) associated with nucleic acid
      decreased obviously; (2) The peak intensity ratio at Amide I, II (I1647/I1541)
      decreased; (3) The peak intensities at 1456 cm(-1) and 1398 cm(-1) showed a
      decreased and an increased trend, respectively; (4) Compared to the peak
      intensity of 1647 cm(-1), the peak intensities at 2852 cm(-1), 2871 cm(-1), 2923
      cm(-1), and 2958 cm(-1) tended to increase, with only a slightly increased
      tendency in peak intensity of 2871 cm(-1). CONCLUSION: FTIR spectroscopy may be
      potentially used as an effective method for estimating the PMI in medicolegal
      practice using brain tissue sample.

PMID- 18709847
TI  - [The relationship between the degradation of actin and the postmortem interval in
      rats].
AB  - OBJECTIVE: To observe the degradation of actin in cardiac muscle, brain and
      skeletal muscle of rats after death and to find an objective parameter interval
      (PMI) estimation. METHODS: Twenty eight clear Sprague Dawley rats put into an
      artificial climate incubator (set at 20 degrees C) for 0, 24, 48, 72, The actin
      contents in the above tissues were quantitated by Western-blot Pro Plus 5.0 image
      analysis system, and were then statistically analyzed RESULTS: Actin content in
      all these tissues decreased gradually with prolonged differences between the
      groups was statistically significant (P < 0.05), with fastest, then the lung, the
      spleen, the liver, the kidney, the cardiac muscle order. There was a strong
      correlation between actin degradation and determination (R2) exceeded 0.75 in all
      these tissues. CONCLUSION: degradation, the actin contents in cardiac muscle,
      liver, spleen, lung, kindey, rats decreased gradually with prolonged PMI, which
      may potentially be PMI estimation.

PMID- 18709848
TI  - [Animal model of grading skeletal muscle contusion due to blunt impact in rats].
AB  - OBJECTIVE: To establish a new animal model of grading skeletal muscle contusions
      that could be controllable and repetitive. METHODS: The rats' gastrocnemius was
      injured by a new weight-dropping device designed. The force acting on
      gastrocnemius with a comparatively constant duration and inducing elastic
      deformation of the gastrocnemius was expressed with velocity (v) and deformation
      (DF). Instant velocity was changed to create gastrocnemius contusions.
      Pathological changes of gastrocnemius were graded by the gross and histological
      examinations of 39 rats. RESULTS: At low level of impact (v: 2 m/s, DF: 5.5 mm),
      mild injuries were detected in epimysium and superficial layer of gastrocnemius.
      At moderate level of impact (v: 2.5 m/s, DF: 6.5 mm), the injuries were observed
      in epimysium and whole gastrocnemius. At high level of impact (v: 3 m/s, DF: 7.5
      mm), severe injuries were seen deeper to soleus with more extensive skeletal
      muscle damage. CONCLUSION: Grading of skeletal muscle blunt force contusion is
      created by parameter of velocity and muscle deformation. The model could be used
      for further research on skeletal muscle contusions.

PMID- 18709849
TI  - [The expression of NGF after rat diffuse axonal injury].
AB  - OBJECTIVE: To study the expression of nerve growth factor (NGF) in diffuse axonal
      injury (DAI) in rat. METHODS: Eighty SD rats were used and samples were taken at
      1 h, 3 h, 6 h, 12 h, 24 h, 48 h, 3 d, and 7 d after brain injury. The expressions
      of NGF in cerebral cortex, thalamus, cerebellum, and hippocampus were studied
      with immunohistochemistry and compared with normal group and sham operation
      group. RESULTS: Low expression of NGF was observed in normal group and sham
      operation group. The expression of NGF increased 1 h after injury, peaked at 12
      h, and returned to basal level at day 7. CONCLUSION: NGF is involved in repair of
      DAI. The changes of NGF expression following DAI may be applied to estimate the
      post-injury time interval of the brain in forensic medicine.

PMID- 18709850
TI  - [Expression of myocardial collagen I in early acute myocardial ischemic of
      human].
AB  - OBJECTIVE: To estimate the significance of myocardial collagen I in the early
      acute myocardial ischemia of human. METHODS: The myocardial paraffin block had
      normal group, early myocardial ischemia group and myocardial infarction group.
      The myocardial collagen I was observed with immunohistochemical staining and
      analyzed by half-quantity. RESULTS: The similar expression of collagen I was
      observed in the cytoplasm and nucleolus in two groups. CONCLUSION: The collagen I
      appeared in the myocardium of early acute myocardial ischemia of human. It may be
      an important index for postmortem diagnosis of the early acute myocardial
      ischemia.

PMID- 18709851
TI  - [Repaired ulnar nerve and effect on its innervating muscles in rat].
AB  - OBJECTIVE: To study the morphological changes of the rat claw inner skeletal
      muscle after ulnar nerve injury at different sections and different recovery
      times. METHODS: Forty-two adult male Sprague-Dawley rats were selected and placed
      randomly in seven groups. After establishing model of injury and repair of claw
      inner skeletal muscle by cutting off the ulnar nerve, the muscle wet weight,
      cross section area of myocytes, and collagen fibers were measured. RESULTS: Claw
      inner skeletal muscle atrophy was significantly less in experiment groups
      compared with the control groups after ulnar nerve injuries. The functional
      recovery was better in the early repair groups than the late repair group.
      Collagen fibers increased slowly in earlier stage, but more significantly in late
      stage. The muscle atrophy was similar in wrist and elbow after ulnar nerve injury
      during the same recovery period. CONCLUSION: The function can recover completely
      or partly in early repair groups, but not quite effective in late stage. The
      increase of collagen fiber is one of the reasons to undermine the recovery effect
      of damaged ulnar nerve. There is no obvious difference of effect on the
      morphological changes of the rat claw inner skeletal muscle no matter the ulnar
      nerve is injured at wrist or elbow.

PMID- 18709852
TI  - [Trend of bone development of adolescent at 14 years old].
AB  - OBJECTIVE: To describe characteristic of hand-wrist bone development in
      adolescents of 14 years old in China, and to estimate trend of bone development
      of them. METHODS: A total of 109 adolescents of 14 years was selected as subjects
      (males: 53, females: 56). X-rays examination of their left hand-wrist bone were
      performed and analyzed. The development characteristics of each position in
      accordance with Gu's mapping of skeletal age were compared with Gu's results and
      ours. RESULTS: Compared with Gu's, osteoepiphysis of distal radius, the first
      metacarpal bone, the fourth proximal phalanx were more advanced in boys,
      osteoepiphysis of distal radius, the second-fifth metacarpal bones, the first
      fifth proximal phalanxs, and the second-fifth middle phalanxs were more advanced
      in girls. CONCLUSION: The results suggested that a forward trend of 14 years old
      adolescents bone development currently exists in our country, especially in
      girls. As an important age of criminal responsibility, this forward trend of
      development of bones among adolescents currently should be kept in mind when
      estimating bone age of criminals.

PMID- 18709853
TI  - [Species identification of biomaterials by amplifying 12S rRNA gene].
AB  - OBJECTIVE: To establish an accurate, simple, quick, specific and sensitive method
      for species identification by amplifying 12S rRNA gene with the same reaction
      system. METHODS: Based on the downloaded 12S rRNA gene sequences of eleven
      species (human, chicken, duck, goose, pig, rabbit, rat, sheep, bull, dog and
      goat) from GenBank, a pair of universal primers to eleven species and three pairs
      of specific primers to human, chicken and duck were designed. The amplicons
      amplified with universal primers were used for internal controls, and the
      amplicons amplified with specific primers were used as identification of human,
      chicken and duck. DNA was extracted from various samples including blood stains,
      fresh or freezing muscles, heat-treated muscles and hairs. Both single DNA of
      human, chicken or duck and mixed DNA of any two kinds of them were amplified.
      RESULTS: The lengths of universal amplicons were about 400 bp. The lengths of
      specific amplicons were 163 bp for human, 286 bp for chicken, and 374 bp for
      duck, respectively. No cross amplification was observed, indicating a high
      specificity of the specific primers. The identification rate was 100% for human,
      99% for chicken, and 100% for duck, respectively. The detection sensitivity
      ranged from 2.5 pg to 200 pg of DNA concentration depending on species, even in
      mixtures of different species DNA without interference. CONCLUSION: The method
      established could identify different species under the same reaction system.

PMID- 18709854
TI  - [A new method for SNP typing based on allele specific PCR].
AB  - OBJECTIVE: To establish a new method of SNP typing. METHODS: Based on the
      principle of allele specific PCR and capillary electrophoresis technique, 11
      diallelic SNP loci were selected and two forward primers with different length
      were designed for each SNP, with their 3' ends matched to the two alleles,
      respectively. An artificially mismatched base was also introduced into the third
      or fourth base in the 3' end area of the two forward primers in order to enhance
      the specificity of amplification. A common reverse primer was designed 100-300 bp
      away from the forward primers, and labeled with fluorescence. The PCR products
      were separated and analyzed by ABI Prism 310 Genetic Analyzer after all of the 11
      SNPs were multiply amplified. RESULTS: A single product peak was observed while
      the SNP was homozygous, and two product peaks with different height were observed
      while the SNP was heterozygous. The length of PCR products was different with the
      different SNPs. According to the length of the products and the number of the
      product peaks, the genotypes of the 11 SNPs can simultaneously be analyzed, and
      the results were in accordance with the direct sequencing. CONCLUSION: Fragment
      length discrepant allele specific fluorescence labeled multi-PCR (FLDASFLM-PCR)
      is a simple, rapid and efficient new method for SNP typing.

PMID- 18709855
TI  - [Persistent vegetative state caused by non-brain damage and its forensic
      assessment].
AB  - Persistent vegetative state (PVS) is described as one of the complications of
      brain damage in the current forensic science literatures. PVS unrelated to brain
      damage, however, is not uncommon in daily forensic practice. Currently, only
      "Assessment for Body Impairment of the Injured in Road Traffic Accident"
      designates PVS as one of its items under the section of "Brain, Spinal Cord, and
      Nerves Injury." Therefore, it is difficult to assess the damage and disability in
      PVS, especially PVS due to non-brain damage. Based on a case of PVS caused by
      chest injury in combination with relevant literature review, this paper provides
      a summary on the general information, etiology, pathogenesis, clinical
      manifestation, diagnosis and differential diagnosis of PVS, as well as a
      guideline for its forensic assessment.

PMID- 18709856
TI  - [Accurate determination of wound depth with ultrasound and its forensic
      significance].
AB  - Accurate determination of the wound depth has long been a difficult task in
      forensic medicine due to lack of technology. Nowadays, the depth of the wound can
      be accurately determined by using high frequency 2-D ultrasound and Color Doppler
      Flow Imaging (CDFI). Two typical cases with ultrasonic images were reported to
      show the importance of ultrasound technology in forensic medicine. The new
      technology provides scientific evidence of the injury assessment.

PMID- 18709857
TI  - [Advances of the study of sarcosaphagous insects in forensic medicine].
AB  - The study of sarcosaphagous insects is a subspecialty in forensic medicine based
      on the knowledge of entomology. It could help to determine the time of death,
      especially the postmortem interval in decomposed cases. This paper explores its
      history, species and erosion process of sarcosaphagous insects. It reviews the
      species identifying methods with molecular biology and entomological morphology.
      Details of its application in estimating postmortem interval in recent years and
      study of sarcosaphagous insects in the field of forensic medicine are summarized.

PMID- 18709858
TI  - [Analysis of genetics and genomics of short tandem repeat loci commonly used in
      Kinship Testing].
AB  - Since the foundation of FBI laboratory's Combined DNA Index System (CODIS) a
      decade ago, the 13 CODIS STR loci of the system as well as the recently developed
      Penta D, Penta E, D2S1338 and D19S433 loci have been widely used by kinship
      testing laboratories worldwide and have played an important role in the field of
      Kinship Testing and in construction of criminal database. This article
      systemically analyzed the characteristics of STR loci information and its genomic
      information analyzed through search of a variety of database including Webof
      Knowledge, Elsevier and Internet resources. The up-to-date application of the
      commonly used STR loci in recent years is also reviewed.

PMID- 18709859
TI  - Consumer-friendly EOBs from health plans? Not likely.

PMID- 18709860
TI  - Addressing roadblocks to hospital-physician alignment.
AB  - In Lefton's June column, he outlined the need for meaningful healthcare reform
      and presented 14 reform strategies. This month, he examines two of these 14
      strategies - both of which relate to hospital-physician alignment.

PMID- 18709861
TI  - Strategies and tools for improving transcription and documentation.
AB  - Failure to accurately document care provided is a significant threat to hospital
      revenue and compliance. What's more, it's only expected to become more important
      as documentation efforts grow increasingly more sophisticated to respond to the
      requirements of severity-based payment, as is being seen with Medicare severity
      based diagnosis-related groups (MS-DRG). With this in mind, the following
      discussion, sponsored by 3M Health Information Systems, explores use of process
      change and technology to improve transcription and clinical documentation
      activities. Hospital executives also share their strategies for engaging
      physicians in these efforts and optimizing technology investments.

PMID- 18709862
TI  - The rewards of accurate clinical documentation.
AB  - Pittsburgh's Jefferson Regional Medical Center took the following steps to
      improve the accuracy of its clinical documentation: Convinced staff of the need
      to improve accuracy; Educated staff and physicians; Communicated responsibility
      and accountability; Tracked and bench-marked key data.

PMID- 18709863
TI  - Lessons learned with MS-DRGs: getting physicians on board for success.
AB  - To get physicians on board with a clinical documentation program: Explain what
      the government is trying to accomplish with changes to the prospective payment
      system; Connect codes and quality report cards; Enlist a physician champion;
      Conduct an MS-DRG financial impact study and share the results with physicians;
      Establish a clinical documentation improvement/integrity team; Provide solid
      rationale and data to back up requests.

PMID- 18709864
TI  - Managing risk in a challenging financial environment.
AB  - Five strategies can help hospital financial leaders balance their organizations'
      financial and risk positions: Understand the hospital's financial condition;
      Determine the desired level of risk; Consider total risk; Use a portfolio
      approach; Explore best-case/worst-case scenarios to measure risk.

PMID- 18709865
TI  - The failure of AHERF: 5 important lessons.
AB  - Important lessons from AHERF's downfall: Strong governance and oversight of
      management are needed to ensure accountability; Disciplined growth strategies
      need to be supported by rigorous financial planning and feasibility analysis;
      Physician integration is critical to grow market share, but needs to be
      methodical and measured; Robust information systems are necessary to manage
      costs, maximize revenue, and provide differentiation in quality and clinical
      outcomes; Disclosure of the financial performance of all of a health system's
      operations creates greater transparency and builds credibility.

PMID- 18709866
TI  - Liability-driven investing: an enterprise risk management strategy.
AB  - Hospitals that understand their risks and how to address them, and can
      communicate thisto rating agencies, can improve their opportunities in the
      capital markets. Evaluating global risk requires that healthcare financial
      executives consider risks in the context of one another as well as the
      organization's overall strategic plan.

PMID- 18709867
TI  - Grasping recent changes to the PRRB appeal process.
AB  - The amended PRRB rules will significantly change the way providers prepare for
      and prosecute appeals to the board. All providers and chain organizations should
      take stock of their longstanding as well as upcoming appeal issues to preserve
      their rights to pursue proper Medicare reimbursement. The rules' emphasis on
      front-end work by providers could require significant process changes for
      organizations.

PMID- 18709868
TI  - Concierge services: helping employees and the bottom line.
AB  - Difficulty balancing work and personal life can add to workers' stress level.
      Inevitably, handling personal needs can conflict with work commitments. Some
      healthcare organizations are offering concierge services to help employees manage
      some of their time-consuming personal chores as well as provide some corporate
      services.

PMID- 18709869
TI  - Want independent validation and assurance? Ask for a SAS-70.
AB  - The AICPA's Statement on Auditing Standards No.70, Service Organizations
      addresses CPA audits of service providers conducted to verify that a provider has
      adequate controls over its operations. Hospitals should request a SAS-70, the
      report produced by such an audit, from all of their third-party service
      providers. SAS-70s can be issued for a specific date or for a six-month period,
      and they typically consist of three sections: a CPA opinion, a description of
      controls, and information about the design of the controls.

PMID- 18709870
TI  - Balance sheet assets and credit rating: what's the connection?
AB  - Healthcare organizations should take into consideration the impact that portfolio
      investment decisions have on key credit metrics.

PMID- 18709871
TI  - The rise of the bank infomediary in health care.
AB  - Banks are evolving in four key areas that collectively comprise the rise of a
      "bank infomediary": Efficient administrative processing; Medical Internet; Health
      information broker; Community care platform.

PMID- 18709872
TI  - Clinical documentation specialist staffing requirements.

PMID- 18709873
TI  - Leading innovation in a risk-averse healthcare environment.

PMID- 18709874
TI  - HIEs: survival of the fittest.

PMID- 18709876
TI  - Supply chain benchmarking.

PMID- 18709875
TI  - What would you do? Affiliate, merge, or stay independent?

PMID- 18709877
TI  - Folate and vitamin B12 deficiencies: proceedings of a WHO technical consultation
      held 18-21 October, 2005, in Geneva, Switzerland. Introduction.

PMID- 18709878
TI  - Folate and vitamin B12 metabolism: overview and interaction with riboflavin,
      vitamin B6, and polymorphisms.
AB  - This paper provides a general review on folate and vitamin B12 nutrition and
      metabolism and the metabolic interrelationship between these vitamins. The
      effects of some common polymorphisms in folate and vitamin B12 genes and the
      influence of vitamin B6 and riboflavin status on folate and vitamin B12
      metabolism are also discussed.

PMID- 18709879
TI  - Causes of vitamin B12 and folate deficiency.
AB  - This review describes current knowledge of the main causes of vitamin B12 and
      folate deficiency. The most common explanations for poor vitamin B12 status are a
      low dietary intake of the vitamin (i.e., a low intake of animal-source foods) and
      malabsorption. Although it has long been known that strict vegetarians (vegans)
      are at risk for vitamin B12 deficiency, evidence now indicates that low intakes
      of animal-source foods, such as occur in some lacto-ovo vegetarians and many less
      industrialized countries, cause vitamin B12 depletion. Malabsorption of the
      vitamin is most commonly observed as food-bound cobalamin malabsorption due to
      gastric atrophy in the elderly, and probably as a result of Helicobacter pylori
      infection. There is growing evidence that gene polymorphisms in transcobalamins
      affect plasma vitamin B12 concentrations. The primary cause of folate deficiency
      is low intake of sources rich in the vitamin, such as legumes and green leafy
      vegetables, and the consumption of these foods may explain why folate status can
      be adequate in relatively poor populations. Other situations in which the risk of
      folate deficiency increases include lactation and alcoholism.

PMID- 18709880
TI  - Review of the magnitude of folate and vitamin B12 deficiencies worldwide.
AB  - Human deficiencies of folate and vitamin B12 result in adverse effects which may
      be of public health significance, but the magnitude of these deficiencies is
      unknown. Therefore, we examine the prevalence data currently available, assess
      global coverage of surveys, determine the frequency with which vitamin status
      assessment methods are used, and identify patterns of status related to
      geographical distribution and human development. Surveys were identified through
      PubMed and the Vitamin and Mineral Nutrition Information System at the World
      Health Organization (WHO). Since different thresholds were frequently used to
      define deficiency, measures of central tendency were used to compare blood
      vitamin concentrations among countries. The percentage of countries with at least
      one survey is highest in the WHO Regions of South-East Asia and Europe. Folate
      and vitamin B12 status were most frequently assessed in women of reproductive age
      (34 countries), and in all adults (27 countries), respectively. Folate status
      assessment surveys assessed plasma or serum concentrations (55%), erythrocyte
      folate concentrations (21%), or both (23%). Homocysteine was assessed in one
      third of the surveys of folate and vitamin B12 status (31% and 34% respectively),
      while methylmalonic acid was assessed in fewer surveys of vitamin B12 status
      (13%). No relationship between vitamin concentrations and geographical
      distribution, level of development, or population groups could be identified, but
      nationally representative data were few. More representative data and more
      consistent use of thresholds to define deficiency are needed in order to assess
      whether folate and vitamin B12 deficiencies are a public health problem.

PMID- 18709881
TI  - Indicators for assessing folate and vitamin B12 status and for monitoring the
      efficacy of intervention strategies.
AB  - Deficiencies of folate or of vitamin B12 are widespread and constitute a major
      global burden of morbidity affecting all age groups. Detecting or confirming the
      presence of folate or vitamin B12 deficiency and distinguishing one from the
      other depends, ultimately, on laboratory testing. Tests to determine the presence
      of folate or vitamin B12 deficiency are used singly or in combination to
      establish the nutritional status and prevalence of deficiencies of the vitamins
      in various populations. The efficacy of interventions through the use of
      fortification or supplements is monitored using the same laboratory tests. Tests
      currently in use have limitations that can be either technical or have a
      biological basis. Consequently, each single test cannot attain perfect
      sensitivity, specificity, or predictive value. Laboratory indicators of vitamin
      B12 or folate status involve measurement of either the total or a physiologically
      relevant fraction of the vitamin in a compartment such as the blood. Thus, assays
      to measure vitamin B12 or folate in plasma or serum as well as folate in red
      blood cells are in widespread use, and more recently, methods to measure vitamin
      B12 associated with the plasma binding protein transcobalamin
      (holotranscobalamin) have been developed. Alternatively, levels of surrogate
      biochemical markers that reflect the metabolic function of the vitamin can be
      used. Surrogates most commonly used are plasma homocysteine, for detection of
      either vitamin B12 or folate deficiency and methylmalonic acid for detection of
      vitamin B12 deficiency. The general methods as well as their uses, indications,
      and limitations are presented.

PMID- 18709882
TI  - The use of blood concentrations of vitamins and their respective functional
      indicators to define folate and vitamin B12 status.
AB  - In recent years there has been growing interest in the vitamins folic acid and
      vitamin B12 because of the realization that the status of these vitamins in
      populations is less than adequate, and that such inadequacy may be linked to
      adverse public health outcomes. This concern has prompted the United States,
      Canada, and other countries to fortify grain products with folic acid, while
      additional countries are considering doing so in the near future. This
      presentation provides a new approach which relies on the combination of the
      concentrations in blood of vitamins and their respective functional indicators to
      establish cutoff points for assessing folate and vitamin B12 status in
      populations. The premise is based on the fact that the relationship between
      plasma vitamin concentrations and their respective functional indicators is
      inverse and biphasic, with a steep slope at low concentrations of the vitamin and
      a more moderate slope at higher plasma vitamin concentrations. We propose that
      the intersection of these two slopes be used as a guideline for assessing the
      status of these vitamins and the adequacy of fortification programs. The cutoff
      would be 10 nmol/L for serum folate and 340 nmol/L for red blood cell folate,
      based on lowest plasma homocysteine. For serum vitamin B12, the cutoff would be
      150 pmol/L based on lowest methylmalonic acid and 300 pmol/L based on lowest
      homocysteine.

PMID- 18709883
TI  - A high prevalence of biochemical evidence of vitamin B12 or folate deficiency
      does not translate into a comparable prevalence of anemia.
AB  - Based on biochemical evidence, a high prevalence of biochemical evidence of
      vitamin B12 or folate deficiency has been reported in a number of areas in the
      world. The evidence that these biochemical abnormalities lead to a comparable
      prevalence of anemia is reviewed. The overall contribution of vitamin B12
      deficiency to the global burden of anemia is probably not significant, except
      perhaps in women and their infants and children in vegetarian communities. In
      developed countries, folate-deficiency anemia is uncommon. In some developing
      countries, this anemia is still seen, but there are no comprehensive data on the
      relative prevalence compared with anemia due to malaria, iron-deficiency,
      hemoglobinopathy, and HIV disease. It seems unlikely that folate deficiency makes
      a major contribution to the burden of anemia in developing countries. Iron
      deficiency anemia may coexist with vitamin B12 and especially folate deficiency,
      and may confound the hematological features of the vitamin deficiencies whose
      prevalence would then be underestimated. Supplementation of the diet of pregnant
      women with folic acid can virtually eliminate folate-deficiency anemia in these
      women. There are very few data on the hematological effect of vitamin B12
      supplementation or fortification at the population level. The addition of vitamin
      B12 to the supplementation of the diet of pregnant women with iron and folic acid
      does not produce an increased hematological response, at least in nonvegetarian
      populations. There are numerous reports of the effect of folic acid fortification
      of food on tests of folate status, but only a single published report on the
      hematological response was found.

PMID- 18709884
TI  - Gene-nutrient interactions: importance of folic acid and vitamin B12 during early
      embryogenesis.
AB  - The role that nutritional factors play in mammalian development has received
      renewed attention over the past two decades as the scientific literature has
      exploded with reports that folic acid supplementation in the periconceptional
      period can protect embryos from a number of highly significant malformations. As
      is often the case, the relationship between B vitamin supplementation and
      improved pregnancy outcomes is more complicated than initially perceived, as the
      interaction between nutritional factors and selected genes must be considered. In
      this review, we attempt to summarize the complex clinical and experimental
      literature on nutritional factors, their biological transport mechanisms, and
      interactions with genetic polymorphisms that impact early embryogenesis. While
      not exhaustive, our goal was to provide an overview of important gene-nutrient
      interactions, focusing on folic acid and vitamin B12, to serve as a framework for
      understanding the multiple roles they play in early embryogenesis.

PMID- 18709885
TI  - Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant,
      and child development.
AB  - The importance of folate in reproduction can be appreciated by considering that
      the existence of the vitamin was first suspected from efforts to explain a
      potentially fatal megaloblastic anemia in young pregnant women in India. Today,
      low maternal folate status during pregnancy and lactation remains a significant
      cause of maternal morbidity in some communities. The folate status of the neonate
      tends to be protected at the expense of maternal stores; nevertheless, there is
      mounting evidence that inadequate maternal folate status during pregnancy may
      lead to low infant birthweight, thereby conferring risk of developmental and long
      term adverse health outcomes. Moreover, folate-related anemia during childhood
      and adolescence might predispose children to further infections and disease. The
      role of folic acid in prevention of neural tube defects (NTD) is now established,
      and several studies suggest that this protection may extend to some other birth
      defects. In terms of maternal health, clinical vitamin B12 deficiency may be a
      cause of infertility or recurrent spontaneous abortion. Starting pregnancy with
      an inadequate vitamin B12 status may increase risk of birth defects such as NTD,
      and may contribute to preterm delivery, although this needs further evaluation.
      Furthermore, inadequate vitamin B12 status in the mother may lead to frank
      deficiency in the infant if sufficient fetal stores of vitamin B12 are not laid
      down during pregnancy or are not available in breastmilk. However, the
      implications of starting pregnancy and lactation with low vitamin B12 status have
      not been sufficiently researched.

PMID- 18709886
TI  - Public health significance of elevated homocysteine.
AB  - Homocysteine is a sulfur amino acid whose metabolism stands at the intersection
      of two pathways: remethylation, which requires folic acid and vitamin B12
      coenzymes; and transsulfuration, which requires pyridoxal-5'-phosphate, the
      vitamin B6 coenzyme. Data from a number of laboratories suggest that mild
      elevations of homocysteine in plasma are a risk factor for occlusive vascular
      disease. In the Framingham studies, we have shown that plasma homocysteine
      concentration is inversely related to the intake and plasma levels of folate and
      vitamin B6 as well as vitamin B12 plasma levels. Almost two-thirds of the
      prevalence of high homocysteine is attributable to low vitamin status or intake.
      Elevated homocysteine concentrations in plasma are a risk factor for prevalence
      of extracranial carotid-artery stenosis > or = 25% in both men and women.
      Prospectively elevated plasma homocysteine is associated with increased total and
      cardiovascular mortality, increased incidence of stroke, increased incidence of
      dementia and Alzheimer's disease, increased incidence of bone fracture, and
      higher prevalence of chronic heart failure. It was also shown that elevated
      plasma homocysteine is a risk factor for preeclampsia and maybe neural tube
      defects (NTD). This multitude of relationships between elevated plasma
      homocysteine and diseases that afflict the elderly, pregnant women, and the
      embryo points to the existence ofa common denominator which may be responsible
      for these diseases. Whether this denominator is homocysteine itself or
      homocysteine is merely a marker, remains to be determined.

PMID- 18709887
TI  - Effects of vitamin B12 and folate deficiency on brain development in children.
AB  - Folate deficiency in the periconceptional period contributes to neural tube
      defects; deficits in vitamin B12 (cobalamin) have negative consequences on the
      developing brain during infancy; and deficits of both vitamins are associated
      with a greater risk of depression during adulthood. This review examines two
      mechanisms linking folate and vitamin B12 deficiency to abnormal behavior and
      development in infants: disruptions to myelination and inflammatory processes.
      Future investigations should focus on the relationship between the timing of
      deficient and marginal vitamin B12 status and outcomes such as infant growth,
      cognition, social development, and depressive symptoms, along with prevention of
      folate and vitamin B12 deficiency.

PMID- 18709888
TI  - Effects of folate and vitamin B12 on cognitive function in adults and the
      elderly.

PMID- 18709889
TI  - The worldwide challenge of the dementias: a role for B vitamins and homocysteine?
AB  - Dementia has reached epidemic proportions, with an estimated 4.6 million new
      cases worldwide each year. With an aging world population, the prevalence of
      dementia will increase dramatically in the next few decades. Of the predicted 114
      million who will have dementia in 2050, about three-quarters will live in less
      developed regions. Although strongly age-related, dementia is not an inevitable
      part of aging but is a true disease, caused by exposure to several genetic and
      nongenetic risk factors. Prevention will be possible when the nongenetic risk
      factors have been identified. Apart from age, more than 20 nongenetic risk
      factors have been postulated, but very few have been established by randomized
      intervention studies. Elevated blood concentrations of total homocysteine and low
      normal concentrations of B vitamins (folate, vitamin B12, and vitamin B6) are
      candidate risk factors for both Alzheimer's disease and vascular dementia.
      Seventy-seven cross-sectional studies on more than 34,000 subjects and 33
      prospective studies on more than 12,000 subjects have shown associations between
      cognitive deficit or dementia and homocysteine and/or B vitamins. Biologically
      plausible mechanisms have been proposed to account for these associations,
      including atrophy of the cerebral cortex, but a definite causal pathway has yet
      to be shown. Raised plasma total homocysteine is a strong prognostic marker of
      future cognitive decline, and is common in world populations. Low-normal
      concentrations of the B vitamins, the main determinant of homocysteine
      concentrations, are also common and occur in particularly vulnerable sections of
      the population, such as infants and elderly. Large-scale randomized trials of
      homocysteine-lowering vitamins are needed to see if a proportion of dementia in
      the world can be prevented.

PMID- 18709890
TI  - Public health significance of supplementation or fortification of grain products
      with folic acid.

PMID- 18709891
TI  - Efficacy and safety of fortification and supplementation with vitamin B12:
      biochemical and physiological effects.
AB  - Long known as an uncommon but serious medical disorder requiring medical
      management, vitamin B12 deficiency is now seen to be common worldwide, but it is
      in a quite different form than traditionally envisioned. Most of the newly
      recognized deficiency is subclinical in nature, its health impact and natural
      history are uncertain, and its prevalence has been greatly inflated by also
      including persons with "low-normal" vitamin B12 levels, few of whom are
      deficient. The spread of folic acid fortification has also introduced concerns
      about folate's potentially adverse neurologic consequences in persons with
      undetected vitamin B12 deficiency. Fortification with vitamin B12 may prove more
      complicated than fortification with folic acid, however, because the
      bioavailability of vitamin B12 is limited. Bioavailability for those who need the
      vitamin B12 the most is especially poor, because they often have malabsorption
      affecting either classical intrinsic factor-mediated absorption or food-vitamin
      B12 absorption. Moreover, new evidence shows that many elderly persons respond
      poorly to daily oral doses under 500 microg (1 microg = 0.74 nmol), even if they
      do not have classical malabsorption, which suggests that proposed fortification
      with 1 to 10 microg may be ineffective. Those least in need of vitamin B12
      usually have normal absorption and are thus at greatest risk for whatever unknown
      adverse effects of high-dose fortification might emerge, such as the effects of
      excess accumulation of cyanocobalamin. Studies are needed to define the still
      unproven health benefits of vitamin B12 fortification, the optimal levels of
      fortification, the stability of such fortification, interactions with other
      nutrients, and any possible adverse effects on healthy persons. The answers will
      permit formulation of appropriately informed decisions about mandatory
      fortification or (because fortification may prove a poor choice) about targeted
      supplementation in subpopulations with special needs for additional vitamin B12,
      such as vegetarians, nursing mothers, and the elderly.

PMID- 18709892
TI  - Review of interventions for the prevention and control of folate and vitamin B12
      deficiencies.
AB  - Folate and vitamin B12 deficiencies represent important and evolving global
      health challenges that contribute to the global burden of anemia, neurologic
      conditions, neurodevelopmental disorders, and birth defects. We present a review
      of population-based programs designed to increase consumption of folates and
      vitamin B12. A folic acid supplementation program targeting couples prior to
      marriage in China has led to optimal consumption of supplements containing folic
      acid and a significant reduction of neural tube defects (NTD). Supplementation
      programs that use mass community education show some promise, but have not been
      shown to be as effective as targeted education. The success of supplementation
      programs hinges on a strong and persistent educational component and access to
      the supplements. Fortification with folic acid has been shown to reduce the
      prevalence of NTD in the countries where it has been implemented. Challenges to
      fortification programs include identifying the appropriate delivery vehicles,
      setting the optimal fortification level, sustaining the quality assurance of the
      fortification level, and addressing regulatory challenges and trade barriers of
      commercially fortified flours. Supplementation and fortification are cost
      effective and viable approaches to reducing the burden of NTD, anemia, and other
      conditions resulting from folate deficiency. The experience with interventions
      involving folic acid could provide a model for the subsequent development of
      supplementation and fortification programs involving vitamin B12.

PMID- 18709893
TI  - National Neural Tube Defects Prevention Program in China.
AB  - Neural tube defects (NTD) are among the most common and devastating birth
      defects. Annually, in China, between 80,000 and 100,000 pregnancies result in
      children born with NTD. Northern China has the highest known rate of NTD in the
      world. Birth defects are becoming the leading cause of infant mortality in the
      urban and developed areas in China. The results of studies conducted in the early
      1990s and early 2000s showed significant geographic and seasonal variations of
      folate status among Chinese women of childbearing age, with lower serum and red
      blood cell folate levels in northern China. In the north, 32% to 35% of women had
      low plasma folate and low red blood cell folate, and folate levels were
      significantly lower in spring than in fall. Since 1993, Peking University Health
      Science Center (formerly Beijing Medical University), collaborating with the US
      Centers for Disease Control and Prevention (CDC), has conducted a large-scale
      study to evaluate a public health campaign in China among women preparing for
      marriage in order to determine the effectiveness of daily supplementation of 400
      microg of folic acid alone in preventing NTD in both the north and the south of
      China. The results showed that among the fetuses or infants of the women who took
      periconceptional folic acid, the reduction in risk of NTD was 85% in the northern
      region and 40% in the southern region. Daily intake of 400 microg of folic acid
      may also reduce the risk of nonsyndromic orofacial clefts. We found no evidence
      that daily consumption of folic acid before and during early pregnancy influenced
      the risk of miscarriage or twinning. In 2001, the Chinese Ministry of Health and
      the Chinese Disabled Person Federation released a National Action Plan for
      Reducing Birth Defects and Disabilities in China for 2002-2010. The Action Plan
      aims to improve birth outcomes, to reduce infant mortality by reducing the risk
      of birth defects and disabilities, and to ensure that every baby is born healthy.

PMID- 18709894
TI  - Folic acid for the prevention of neural tube defects: the Danish experience.
AB  - Evidence from controlled trials suggests that ingestion of 0.4 mg of folic acid
      per day in the periconceptional period is effective in preventing neural tube
      defects (NTD). For this reason, most countries recommend that women planning
      pregnancy take folic acid supplements in the periconceptional period, and some
      countries even fortify stable foods with folic acid. Denmark exemplifies a
      country with a relatively conservative attitude with respect to taking action in
      these matters. In 1999, a national information campaign was launched that
      recommended women planning pregnancy take 0.4 mg of folic acid
      periconceptionally, but with the moderation that women who eat a healthy diet do
      not need to take folic acid supplement. The campaign was repeated during 2001.
      The results of the latter campaign were evaluated by using data from a national
      survey among pregnant women conducted simultaneously with the campaign by the
      Danish National Birth Cohort. An increase in the proportion of folic acid users
      took place concomitantly with the launching of the information events, but the
      increase was limited. Among women who did not plan their pregnancy, a small
      proportion had taken folic acid supplements periconceptionally, and this
      proportion did not change concomitantly with the campaign. Young age and low
      education were factors associated with low likelihood of taking folic acid. It
      seems that different and more efficient actions are needed if a more substantial
      proportion of Danish women and their fetuses are going to benefit from the
      knowledge that folic acid supplementation in the periconceptional period can
      prevent NTD.

PMID- 18709895
TI  - Monitoring of the folic acid supplementation program in the Netherlands.
AB  - In November of 1993, the Dutch government recommended daily folic acid
      supplementation of 0.4 or 0.5 mg for all women planning pregnancy, starting 4
      weeks before conception until 8 weeks after. In 1995, a one-time mass media
      campaign was conducted, and due to this campaign, the use of folic acid in this
      recommended period increased from 4.8% in 1995 to 21% in 1996. Subsequently, no
      structural strategies were undertaken until 2003, and at that time, 22% of lower
      educated women used folic acid in the recommended period. The prevalence of
      neural tube defects (NTD) decreased from 11.44/10,000 before the official
      recommendations to 6.52/10,000 thereafter. Currently, community pharmacies
      proactively approach women before their first pregnancy on the subject of folic
      acid supplementation. This is done by means of a sticker placed on packages of
      oral contraceptives with the text "Child wish?*". "Ask for information about
      folic acid in your pharmacy," and a brochure (leaflet) containing detailed
      information about folic acid. (*"Child wish" refers to women who plan to become
      pregnant.) Data from an explorative, comparative study strongly suggest that this
      intervention is effective. Sustainable education programs through which women are
      informed repeatedly to take folic acid supplements during the periconceptional
      period are urgently needed.

PMID- 18709896
TI  - Establishing safe and potentially efficacious fortification contents for folic
      acid and vitamin B12.
AB  - Determining the micronutrient contents infortified foods depends not only on the
      health goal (additional intake to complement the diet), but also on ensuring that
      fortification does not raise micronutrient intakes beyond the Tolerable Upper
      Intake Level (UL), i.e., the safe limit. Technological incompatibility and cost
      may also restrict the fortification contents. For folic acid, the limiting factor
      is safety, while for vitamin B12, it is cost. However, adequate fortification
      contents that are both safe and efficacious can be estimated for both nutrients.
      In order to obtain the maximum benefit from the fortification programs, three
      different formulas responding to three categories of consumption, as specified by
      the median and 95th percentile of consumption, are proposed. The model presented
      is based on the estimation of a Feasible Fortification Level (FFL), which then is
      used to determine the average, minimum, and maximum contents of the nutrients
      during production, taking into consideration the acceptable variation of the
      fortification process. Finally, the regulatory parameters, which support
      standards and enforcement, are calculated by reducing the proportion of the
      nutrient that is degraded during the usual marketing process of the fortified
      food. It is expected that this model will establish a common standard for food
      fortification, and improve the reliability and enforcement procedures of these
      programs. The model was applied to flours as vehicles for folic acid in the
      United States, Guatemala, and Chile. Analysis of the data revealed that, with the
      exception of Chile, where wheat flour consumption is very high and probably
      within a narrow range, supplementation with folic acid is still needed to cover
      individuals at the low end of consumption. This is especially true when the
      difference in flour consumption is too wide, as in the case of Guatemala, where
      the proportional difference between consumption at the 95th percentile of the
      nonpoor group is as high as 100 times the consumption at the 5th percentile of
      the extremely poor group. Adoption of fortification content for staple foods near
      the safe limit brings together the need of restricting the voluntary addition of
      the specific nutrient to other foods and to dietary supplements.

PMID- 18709897
TI  - Efficacy of Canadian folic acid food fortification.
AB  - Canada mandated that cereal grains, especially white flour, be fortified with
      folic acid by mid-1998. Between 0.1 and 0.2 mg of additional synthetic folic acid
      per day has been provided through this initiative. The current paper describes
      how this took place, and the epidemiological effects that occurred in the
      Canadian population, including higher blood folate levels and a decline in the
      prevalence of neural tube defects.

PMID- 18709898
TI  - National food-fortification program with folic acid in Chile.
AB  - The Chilean Ministry of Health legislated to add folic acid (2.2 mg/100 g) to
      wheat flour to reduce the risk of neural tube defects (NTD), beginning in January
      2000. This policy resulted in a significant increase in serum and red blood cell
      folate in women of childbearing age 1 year after fortification. The frequency of
      NTD was studied in all births, both live and stillbirths, in a prospective
      hospital-based design including 25% of national births during 1999-2000
      (prefortification period) and 2001-2002 (postfortification period). During the
      prefortification period, there was a total of 120,566 newborns, and the NTD rate
      was 17.1/10,000 births. During the postfortification period (2001-2002) there was
      a total of 117,704 newborns, and the NTD rate was significantly reduced by 43% to
      9.7/10,000 births (RR = 0.57; 95% CI, 0.45 to 0.71). This implies a reduction of
      43% in the rate of NTD. The costs per NTD case and infant death averted were
      1,200 international dollars (I$) and I$11,000, respectively. The cost per
      disability-adjusted life year (DALY) averted was I$91, or 0.8% of the country's
      per capita GDP. On the overall, fortification resulted in net cost savings of
      I$1.8 million. Fortification of wheat flour with folic acid has proven to be an
      effective and cost saving strategy for the primary prevention of NTD in a middle
      income country in a postepidemiological transition, and in a dramatically short
      period of time.

PMID- 18709899
TI  - Conclusions of a WHO Technical Consultation on folate and vitamin B12
      deficiencies.

PMID- 18709900
TI  - 'Futile care': what to do when your patient insists on chemotherapy that likely
      won't help.
AB  - While there is no generally accepted medical definition of "futile care," many
      factors may play a role in the delivery of chemotherapy to patients who are
      unlikely to benefit. In this review, we consider the roles of both the patient
      and the physician in driving the provision of "futile care" and offer practical
      steps the oncologist can take to avoid it.

PMID- 18709901
TI  - From whole-gland to targeted cryoablation for the treatment of unilateral or
      focal prostate cancer.
AB  - The intermediate and long-term results of primary full-gland cryoablation for
      localized prostate cancer with moderate- and high-risk patients suggests a cancer
      control rate similar to what can be achieved with radiotherapy and surgery, with
      an acceptable rate of complications. A recent shift in the treatment paradigm
      toward unilateral cryoablation (hemiablation) or ablation of unifocal lesion(s)
      in select patients suggests the ability of this approach to maintain a quality of
      life closer to the pretreatment level. However, trials with longer oncologic
      follow-up are needed. The development of more accurate imaging-based techniques
      ie, image-guided prostate biopsy sampling and image-guided prostate cryoablation
      is of paramount importance to selecting appropriate candidates for an organ
      sparing procedure. To make this approach scientifically sound, further
      investigation to establish patient selection criteria, the development of
      molecular and imaging parameters of cryoablative efficacy, and regular careful
      follow-up of these patients is needed.

PMID- 18709902
TI  - Functional assessment of the older patient with cancer.
AB  - Cancer is a disease associated with aging. As the population ages worldwide, the
      number of older adults with cancer is dramatically increasing. In both the
      geriatric and oncology literature, an individual's functional status is one of
      the strongest predictors of overall survival and resource requirement. However,
      the measures traditionally used in oncology practice to assess functional status
      in patients of all ages--and to determine the course of treatment--do not
      identify the subtle degrees of functional impairment that predict morbidity and
      mortality in the geriatric population. This article describes the tools used by
      geriatricians to assess physical function, and outlines their prognostic
      significance for the patient with cancer. Including these tools in daily oncology
      practice could help physicians to better assess and treat vulnerable older
      adults.

PMID- 18709904
TI  - Getting out of dodge.

PMID- 18709903
TI  - Granulocytic sarcoma in a patient with myelodysplastic syndrome.
AB  - Granulocytic sarcomas (GS) are uncommon extramedullary tumors composed of
      immature cells of the granulocytic or myeloid series. Treatment for GS should be
      directed toward the underlying hematologic disorder. There is no standard
      treatment.

PMID- 18709905
TI  - Childhood obesity and parental responsibilities.

PMID- 18709906
TI  - "Are their babies different from ours?" Dutch culture and the Groningen Protocol.

PMID- 18709907
TI  - "Are their babies different from ours?" Dutch culture and the Groningen Protocol.

PMID- 18709908
TI  - "Are their babies different from ours?" Dutch culture and the Groningen Protocol.

PMID- 18709909
TI  - Debating health care reform.

PMID- 18709910
TI  - Debating health care reform.

PMID- 18709911
TI  - Teenage decision-making capacity.

PMID- 18709912
TI  - House calls.

PMID- 18709913
TI  - Jesting pilate.

PMID- 18709914
TI  - "Clean" nuclear energy? Global warming, public health, and justice.

PMID- 18709915
TI  - The romance of the family.

PMID- 18709916
TI  - Prenates, postmorts, and bell-curve dignity.

PMID- 18709917
TI  - A day too long: rethinking physician work hours.

PMID- 18709918
TI  - Children's health inequalities: ethical and political challenges to seeking
      social justice.
AB  - Childhood obesity may have severe long-term consequences for health-indeed, for
      the overall course of a person's life. Do these harms amount to a problem of
      social justice? And if so, what should be done about it? Parents are usually
      granted considerable leeway to make decisions that affect their children's
      health. Social and moral theory has often overlooked the family, however, leaving
      us with an inadequate understanding of parental autonomy and of how social policy
      may influence it.

PMID- 18709919
TI  - Reasons of the heart: emotion, rationality, and the "wisdom of repugnance".
AB  - Much work in bioethics tries to sidestep bedrock questions about moral values.
      This is fine if we agree on our values; arguments about human enhancement suggest
      we do not. One bedrock question underlying these arguments concerns the role of
      emotion in morality: worries about enhancement are derided as emotional and thus
      irrational. In fact, both emotion and reason are integral to all moral judgment.

PMID- 18709920
TI  - Altering the brain and mind.

PMID- 18709921
TI  - The blame game: how to evade the cost problem.

PMID- 18709922
TI  - Physiological responses of Juncus effusus (Rush) to chromium and relevance for
      wastewater treatment in constructed wetlands.
AB  - Constructed wetlands are increasingly applied for industrial wastewater
      treatment. However, current knowledge of the stress responses of helophytes to
      selected toxicants such as dichromate is limited. The goal of the experiments
      presented here was to characterize the physiological response of Juncus effusus
      to different concentrations of dichromate dependent upon the growth and
      constitution of the plants. The growth parameters, shoot length, and dry weight
      already were strongly affected at low dichromate concentrations of approximately
      34 microM. Concentrations of 340 microM impaired chlorophyll fluorescence and a
      decrease in chlorophyll a started at concentrations higher than 170 microM
      dichromate. The concentrations of chlorophyll b and carotenoids also were
      influenced negatively. Thus, the reduction of the pigment content started before
      any obvious influence on the chlorophyll fluorescence. The highest concentration
      of dichromate, which caused no permanent inhibition of growth and photosynthesis,
      was found to be 17 microM K2Cr2O7. In principle, J. effusus is suitable for
      constructed wetlands to treat chromium-containing wastewater. Because the stress
      resistance of J. effusus is limited, the maximum concentration of dichromate in
      the treated wastewater should not exceed 34 microM. The growth parameters, shoot
      length, and dry weight were sensitive to much lower dichromate concentrations and
      did react more quickly than the biochemistry-related parameters chlorophyll
      fluorescence and pigment concentration. Therefore, the example of Juncus effusus
      shows that the use of only biochemical parameters to define concentration limits
      for the treatment of dichromate-containing wastewater can lead to incorrect
      conclusions and result in disturbed long-term operation of the system.

PMID- 18709923
TI  - Pot experiment to study the uptake of Cd and Pb by three Indian mustards
      (Brassica juncea) grown in artificially contaminated soils.
AB  - Most of the metals-contaminated and fallow lands in Taiwan are a result of
      irrigation with illegal effluent of factories. Phytoextraction methods can be
      applied to reach the target of fallow-lands reuse and earn more incomes for
      farmers. In many studies, Indian mustards (Brassica juncea) were planted in the
      metal-contaminated soils to study their suitability in phytoextraction. However,
      the total removal of metals by plants was quite different between accessions. In
      this pot study, three accessions of B. juncea (cv. 182921, cv. 211000, and cv.
      426308) were planted in artificially Cd- or Pb-contaminated soils to investigate
      the differences between them. EDTA was applied to study its effect in increasing
      the bioavailability of Cd and Pb and their uptake by these Indian mustards.
      Experimental result showed that three accessions of Indian mustard can accumulate
      a high concentration of Cd and Pb when growing in the artificially Cd- and Pb
      contaminated soils. Their shoot Cd or Pb concentrations were significantly
      enhanced, resulting from the application of EDTA. Among the three accessions, B.
      juncea cv. 211000 accumulated the highest concentrations of Cd and Pb in their
      shoots compared with B. juncea cv. 182921 and cv. 426308, but its total removal
      was the lowest due to its lower biomass.

PMID- 18709924
TI  - Physiological and biochemical responses of rice (Oryza sativa L.) to phenanthrene
      and pyrene.
AB  - Phenanthrene (Phe) and pyrene (Pyr) are two typical polycyclic aromatic
      hydrocarbons (PAHs) found in contaminated soil. This study investigated
      physiological and biochemical responses of rice (Oryza sativa L.) to PAH stress
      after they were planted in soils contaminated with Phe and Pyr, in the presence
      or absence of a PAH-degrading bacteria (Acinetobacteria sp.). A number of
      parameters including biomass and water, chlorophyll and chlorophyll a/b ratio,
      electrolyte leakage, activities of superoxide dismutase (SOD) and peroxidase, and
      soluble carbohydrate and soluble protein contents were monitored. Results show
      that rice plants have good resistance and tolerance to lower levels of PAHs
      stress, while adding high levels of PAHs to soils resulted in adverse effects on
      rice plants such as a reduction in biomass and damage to photosynthetic function.
      Water content and SOD activities were the most sensitive indicators of PAH stress
      among the observed parameters. Inoculation with PAH-degrading bacteria promoted
      growth and photosynthesis of rice.

PMID- 18709925
TI  - Assessment of potential indigenous plant species for the phytoremediation of
      arsenic-contaminated areas of Bangladesh.
AB  - Soil and water contaminated with arsenic (As) pose a major environmental and
      human health problem in Bangladesh. Phytoremediation, a plant-based technology,
      may provide an economically viable solution for remediating the As-polluted
      sites. The use of indigenous plants with a high tolerance and accumulation
      capacity for As may be a very convenient approach for phytoremediation. To assess
      the potential of native plant species for phytoremediation, plant and soil
      samples were collected from four As-contaminated (groundwater) districts in
      Bangladesh. The main criteria used for selecting plants for phytoremediation were
      high bioconcentration factors (BCFs) and translocation factors (TFs) of As. From
      the results of a screening of 49 plant species belonging to 29 families, only one
      species of fern (Dryopteris filix-mas), three herbs (Blumea lacera, Mikania
      cordata, and Ageratum conyzoides), and two shrubs (Clerodendrum trichotomum and
      Ricinus communis) were found to be suitable for phytoremediation. Arsenic
      bioconcentration and translocation factors > 1 suggest that these plants are As
      tolerant accumulators with potential use in phytoextraction. Three floating
      plants (Eichhornia crassipes, Spirodela polyrhiza, and Azolla pinnata) and a
      common wetland weed (Monochoria vaginalis) also showed high BCF and TF values;
      therefore, these plants may be promising candidates for cleaningup As
      contaminated surface water and wetland areas. The BCF of Oryza sativa, obtained
      from As-contaminated districts was > 1, which highlights possible food-chain
      transfer issues for As-contaminated areas in Bangladesh.

PMID- 18709927
TI  - Using elevated carbon dioxide to enhance copper accumulation in Pteridium
      revolutum, a copper-tolerant plant, under experimental conditions.
AB  - In our survey in the copper (Cu) mining area of China, a sun fern (Pteridium
      revolutum) was found to accumulate 30-567 mg Cu kg(-1) DW (33 samples) in its
      fronds with a large frond biomass. Cu translocation factors in the plants varied
      from 0.09 to 3.88. In a greenhouse pot experiment, the effect of an elevated CO2
      concentration (700 microL L(-1)) on Cu accumulation in plants was studied using
      three fern species (P. revolutum, Pteridium aquilinum, and Pteris vittata) grown
      in the Cu-contaminated soil. P. revolutum showed a higher Cu tolerance but its Cu
      translocation factor was lower than 1. At the elevated CO2 concentration, frond
      biomass of all species was significantly increased, as was the total Cu content
      in the fronds of P. revolutum and P. aquilinum. Our study suggests that P.
      revolutum could serve as a good candidate for phytoextraction of Cu-contaminated
      soils and that doubling the ambient CO2 concentration will facilitate its use in
      phytoextraction.

PMID- 18709926
TI  - Heavy metal pollution in aquatic ecosystems and its phytoremediation using
      wetland plants: an ecosustainable approach.
AB  - This review addresses the global problem of heavymetal pollution originating from
      increased industrialization and urbanization and its amelioration by using
      wetland plants both in a microcosm as well as natural/field condition. Heavymetal
      contamination in aquatic ecosystems due to discharge of industrial effluents may
      pose a serious threat to human health. Alkaline precipitation, ion exchange
      columns, electrochemical removal, filtration, and membrane technologies are the
      currently available technologies for heavy metal removal. These conventional
      technologies are not economical and may produce adverse impacts on aquatic
      ecosystems. Phytoremediation of metals is a cost-effective "green" technology
      based on the use of specially selected metal-accumulating plants to remove toxic
      metals from soils and water. Wetland plants are important tools for heavy metal
      removal. The Ramsar convention, one of the earlier modern global conservation
      treaties, was adopted at Ramsar, Iran, in 1971 and became effective in 1975. This
      convention emphasized the wise use of wetlands and their resources. This review
      mentions salient features of wetland ecosystems, their vegetation component, and
      the pros and cons involved in heavy metal removal. Wetland plants are preferred
      over other bio-agents due to their low cost, frequent abundance in aquatic
      ecosystems, and easy handling. The extensive rhizosphere of wetland plants
      provides an enriched culture zone for the microbes involved in degradation. The
      wetland sediment zone provides reducing conditions that are conducive to the
      metal removal pathway. Constructed wetlands proved to be effective for the
      abatement of heavymetal pollution from acid mine drainage; landfill leachate;
      thermal power; and municipal, agricultural, refinery, and chlor-alkali effluent.
      the physicochemical properties of wetlands provide many positive attributes for
      remediating heavy metals. Typha, Phragmites, Eichhornia, Azolla, Lemna, and other
      aquatic macrophytes are some of the potent wetland plants for heavy metal
      removal. Biomass disposal problem and seasonal growth of aquatic macrophytes are
      some limitations in the transfer of phytoremediation technology from the
      laboratory to the field. However, the disposed biomass of macrophytes may be used
      for various fruitful applications. An ecosustainable model has been developed
      through the author's various works, which may ameliorate some of the limitations.
      The creation of more areas for phytoremediation may also aid in wetlands
      conservation. Genetic engineering and biodiversity prospecting of endangered
      wetland plants are important future prospects in this regard.

PMID- 18709928
TI  - Cadmium accumulation in sunflower plants influenced by arbuscular mycorrhiza.
AB  - In order to investigate the cadmium (Cd) accumulation patterns and possible
      alleviation of Cd stress by mycorrhization, sunflower plants (Helianthus annuus
      L.) were grown in the presence or absence of Cd (20 micromol L(-1)) and
      inoculated or not inoculated with the arbuscular mycorrhizal fungus (AMF) Glomus
      intraradices. No visual symptoms of Cd phytotoxicity were observed; nevertheless,
      in non-mycorrhizal plants the presence of Cd decreased plant growth. The addition
      of Cd had no significant effect on either mycorrhizal colonization or the amount
      of extra-radical mycelia that was produced by the AMF. Cd accumulated mainly in
      roots; only 22% of the total Cd absorbed was translocated to the shoots, where it
      accumulated to an average of 228 mg Cd kg(-1). Although the shoot-to-root ratio
      of Cd was similar in both the AMF inoculated and non-inoculated plants, the total
      absorbed Cd was 23% higher in mycorrhizal plants. Cd concentration in AMF extra
      radical mycelium was 728 microg g(-1) dry weight. Despite the greater absorption
      of Cd, mycorrhizal plants showed higher photosynthetic pigment concentrations and
      shoot P contents. Cd also influenced mineral nutrition, leading to decreased Ca
      and Cu shoot concentrations; N, Fe and Cu shoot contents; and increased S and K
      shoot concentrations. Cd induced guaiacol peroxidase activity in roots in both
      mycorrhizal and non-mycorrhizal plants, but this increase was much more
      accentuated in non-mycorrhizal roots. In conclusion, sunflower plants associated
      with G. intraradices were less sensitive to Cd stress than non-mycorrhizal
      plants. Mycorrhizal sunflowers showed enhanced Cd accumulation and some tolerance
      to excessive Cd concentrations in plant tissues.

PMID- 18709929
TI  - Modeling of heavy metals removal from municipal landfill leachate using living
      biomass of water hyacinth.
AB  - Water Hyacinth, Eichhornia crassipes, a fast-growing floating aquatic macrophyte;
      was used for the removal of heavy metals from a municipal landfill leachate. The
      leachate was spiked with different mixtures of five heavy metals (Cd, Cr, Cu, Pb
      and Ni), at a range of concentrations to cover the ranges reported in literature.
      The initial concentrations of the total heavy metals in leachate ranged from 0.06
      to 5.5 mequiv L(-1). All experiments were carried out in batch reactors in a
      greenhouse environment. The water hyacinth plants showed a very promising ability
      to remove and accumulate these metals from the leachate (24% to 80% removal of
      total heavy metals). Generally, the reduction in concentration of total heavy
      metals followed two distinct patterns, a rapid initial decrease followed by a
      slower decrease. An exponential mathematical model was established to estimate
      the remaining concentration of total heavy metals in the leachate over time for
      the rapid initial decrease. Also, a linear relationship was established to
      estimate the concentration of total heavy metals over time for the slower
      decrease. In addition, Langmuir and Freundlich isotherms were applied to the
      observed data and the constants of each isotherm were obtained.

PMID- 18709930
TI  - Pb and Cd accumulation and phyto-excretion by salt cedar (Tamarix smyrnensis
      Bunge).
AB  - The accumulation and excretion of lead (Pb) and cadmium (Cd) by salt cedar
      (Tamarix smyrnensis Bunge) were investigated in this study. Tamarix smyrnensis
      plants were exposed to the mixtures of Pb and Cd and high salinity for 10 wk.
      Subsequently, Pb and Cd uptake was quantified in the shoots and roots of the
      plants by ICP-AES. In addition, physiological parameters such as biomass
      production, shoot length, plant appearance, and chlorophyll content were
      examined. The roots accumulated the highest amount of Pb. Salinity was found to
      not have an important effect on Pb translocation to the leaves. Cd was
      translocated into the aerial part in a higher portion than Pb. Cd content in
      leaves of T. smyrnensis increased with the increasing salinity. The visible
      toxicity symptoms, if present, were connected only to the high salinity. The
      excretion of Pb and Cd by salt glands was observed and quantified. T. smyrnensis
      excreted a significant amount of metals on the leaf surface. This characteristic
      of salt cedar plants can be viewed as a novel phytoremediation process for the
      remediation of sites contaminated with heavy metals that we have termed "phyto
      excretion."

PMID- 18709931
TI  - Toxicity of arsenic (III) and (V) on plant growth, element uptake, and total
      amylolytic activity of mesquite (Prosopis juliflora x P. velutina).
AB  - The effects of arsenite [As(III)] and arsenate [As(V)] on the growth of roots,
      stems, and leaves and the uptake of arsenic (As), micro- and macronutrients, and
      total amylolytic activity were investigated to elucidate the phytotoxicity of As
      to the mesquite plant (Prosopis juliflora x P. velutina). The plant growth was
      evaluated by measuring the root and shoot length, and the element uptake was
      determined using inductively coupled plasma optical emission spectroscopy. The
      root and leaf elongation decreased significantly with increasing As(III) and
      As(V) concentrations; whereas, stem elongation remained unchanged. The As uptake
      increased with increasing As(III) or As(V) concentrations in the medium. Plants
      treated with 50 mg/L As(III) accumulated up to 920 mg/kg dry weight (d wt) in
      roots and 522 mg/kg d wt in leaves, while plants exposed to 50 mg/L As(V)
      accumulated 1980 and 210 mg/kg d wt in roots and leaves, respectively. Increasing
      the As(V) concentration up to 20 mg/L resulted in a decrease in the total
      amylolytic activity. On the contrary, total amylolytic activity in As(III)
      treated plants increased with increasing As concentration up to 20 mg/L. The
      macro- and micronutrient concentrations changed in As-treated plants. In shoots,
      Mo and K were reduced but Ca was increased, while in roots Fe and Ca were
      increased but K was reduced. These changes reduced the size of the plants, mainly
      in the As(III)-treated plants; however, there were no visible sign of As
      toxicity.

PMID- 18709932
TI  - Phytoextraction of zinc, copper, nickel and lead from a contaminated soil by
      different species of Brassica.
AB  - In a pot culture experiment, five different species of Brassica (Brassica juncea,
      Brassica campestris, Brassica carinata, Brassica napus, and Brassica nigra) were
      grown for screening possible accumulators of heavy metals, viz. Zn, Cu, Ni, and
      Pb. The plants were grown to maturity in a soil irrigated with sewage effluents
      for more than two decades in West Delhi, India. The soil analysis showed enhanced
      accumulation of Zn, Cu, Ni, and Pb in this sewage-irrigated soil. Among all
      species, B. carinata showed the highest concentration (mg kg(-1)) as well as
      uptake (microg pot(-1)) of Ni and Pb at maturity. Although B. campestris showed a
      higher concentration of Zn in its shoots (stem plus leaf), B. carinata extracted
      the largest amount of this metal due to greater biomass production. However, B.
      juncea phytoextracted the largest amount of Cu from the soil. In general, the
      highest concentration and uptake of metal was observed in shoots compared to
      roots or seeds of the different species. Among the Brassica spp., B. carinata cv.
      DLSC1 emerged as the most promising, showing greater uptake of Zn, Ni, and Pb,
      while B. juncea cv. Pusa Bold showed the highest uptake of Cu. The B. napus also
      showed promise, as it ranked second with respect to total uptake of Pb, Zn, and
      Ni, and third for Cu. Total uptake of metals by Brassica spp. correlated
      negatively with available as well as the total soil metal concentrations. Among
      the root parameters, root length emerged as the powerful parameter to dictate the
      uptake of metals by Brassica spp. Probably for the first time, B. carinata was
      reported as a promising phytoextractor for Zn, Ni, and Pb, which performed better
      than B. juncea.

PMID- 18709934
TI  - Data, information, and indicators.

PMID- 18709933
TI  - Nitrogen dioxide at an ambient level improves the capability of kenaf (Hibiscus
      cannabinus) to decontaminate cadmium.
AB  - As reported previously, atmospheric nitrogen dioxide (NO2) at an ambient level
      increased plant size and the contents of cell constituents. We investigated this
      effect of atmospheric NO2 on decontamination of cadmium (Cd) by kenaf (Hibiscus
      cannabinus). Seventeen-day-old seedlings of kenaf were grown in air either with
      NO2 or without NO2. (Plants were exposed to 100 +/- 50 ppb NO2 for 10 d under
      irrigation of 0.1% Hyponex supplemented with 20 microM CdCl2.) Plants were then
      harvested and the biomass of stems, leaves, and roots, as well as the content of
      Cd in the organs, was determined. The stem and root biomass per plant were 1.25
      1.27-fold greater in +NO2 plants than in -NO2 plants. The Cd content per stem was
      more than 30% greater in +NO2 plants than in -NO2 plants.

PMID- 18709935
TI  - Population psychiatric medication prescription rates following a terrorist
      attack.
AB  - INTRODUCTION: While several population-based studies have documented behavioral
      health disturbances following terrorist attacks, a number of mental health
      service utilization analyses present conflicting conclusions. PURPOSE: The
      purpose of this study was to determine if mental health service utilization
      increased following a terrorist attack by assessing changes in psychoactive drug
      prescription rates. METHODS: The rate of selective serotonin reuptake inhibitor
      (SSRI) prescriptions was measured among New York State Medicaid enrollees before
      and after the terrorist attacks of 11 September 2001. The association between
      geographic proximity to the events and changes in the rate of SSRI prescriptions
      around 11 September 2001 was assessed. RESULTS: From September to December 2001,
      among individuals residing within three miles of the World Trade Center site,
      there was an 18.2% increase in the SSRI prescription rate compared to the
      previous eight-month period (p = 0.0011). While there was a 9.3% increase for non
      New York City residents, this change was not statistically significant (p =
      0.74). CONCLUSIONS: There was a quantifiable increase in the dispensing of
      psychoactive drugs following the terrorist attacks of 11 September 2001, and this
      effect varied by geographic proximity to the events. These findings build on the
      growing body of knowledge on the pervasive effects of disasters and terrorist
      events for population health, and demonstrate the need to include mental and
      behavioral health as key components of surge capacity and public health response
      to mass traumas.

PMID- 18709936
TI  - Roadmap for the protection of disaster research participants: findings from the
      World Trade Center Evacuation Study.
AB  - INTRODUCTION: This report addresses the development, implementation, and
      evaluation of a protocol designed to protect participants from inadvertent
      emotional harm or further emotional trauma due to their participation in the
      World Trade Center Evacuation (WTCE) Study research project. This project was
      designed to identify the individual, organizational, and structural
      (environmental) factors associated with evacuation from the World Trade Center
      Towers 1 and 2 on 11 September 2001. METHODS: Following published recommended
      practices for protecting potentially vulnerable disaster research participants,
      protective strategies and quality assurance processes were implemented and
      evaluated, including an assessment of the impact of participation on study
      subjects enrolled in the qualitative phase of the WTCE Study. RESULTS: The
      implementation of a protocol designed to protect disaster study participants from
      further emotional trauma was feasible and effective in minimizing risk and
      monitoring for psychological injury associated with study participation.
      CONCLUSIONS: Details about this successful strategy provide a roadmap that can be
      applied in other post-disaster research investigations.

PMID- 18709937
TI  - Qualitative study of homeowners' emergency preparedness: experiences,
      perceptions, and practices.
AB  - INTRODUCTION: Considerable morbidity, mortality, and costs are associated with
      household emergency situations involving natural hazards and fires. Many
      households are poorly prepared for such emergency situations, and little is known
      about the psychosocial aspects of household emergency preparedness. PROBLEM: The
      aim of this study is to promote a better understanding of homeowners' experiences
      and perceptions regarding household emergency situations and related preparedness
      practices. METHODS: A brief survey was administered and three focus group
      sessions were conducted with homeowners (n = 16) from two metro Atlanta
      homeowners' associations. The survey inquired about basic demographic
      information, personal experience with a natural hazard or fire, and awareness of
      preparedness recommendations. The focus group discussions centered on household
      emergency preparedness perceptions and practices. RESULTS: Participants defined
      household emergency preparedness as being able to survive with basic supplies
      (e.g., water, flashlights) for 48 hours or longer. While most participants had
      sufficient knowledge of how to prepare for household emergency situations, many
      did not feel fully prepared or had not completed some common preparedness
      measures. Concern about protecting family members and personal experience with
      emergency situations were identified as strong motivations for preparing the
      household for future emergencies. CONCLUSIONS: The focus group findings indicate
      that most participants have prepared for household emergency situations by
      discussing the dangers with family members, stockpiling resources, and taking a
      CPR or first-aid class. However, to the extent that behavior is influenced, there
      is a gap between maintaining preparedness levels and internalizing preparedness
      recommendations. Prevention efforts in Georgia should focus on closing that gap.

PMID- 18709938
TI  - Estimation of external blood loss by paramedics: is there any point?
AB  - OBJECTIVES: There are many patient assessment challenges in the prehospital
      setting, especially the estimation of external blood loss. Previous studies of
      experienced paramedics have demonstrated that external blood loss estimation is
      highly inaccurate. The objective of this study was to determine if undergraduate
      paramedic students could accurately estimate external blood loss on four surfaces
      commonly found in the prehospital environment. METHODS: This prospective,
      observational, blinded study used a convenience sample of undergraduate students
      studying at Monash University during 2006. Students were provided with four
      clinical vignettes using four different surfaces and varying simulated blood
      amounts. RESULTS: Accurate estimation occurred with the vinyl simulation (100
      ml), with a mean value of the estimations of 98 ml (95% Confidence Interval (CI)
      84-113 ml). Carpet and concrete surfaces were both associated with large under
      estimations. The carpet simulation (1,000 ml) had a mean value for the
      estimations of 347 ml (95% CI 320-429 ml). The concrete simulation (1,500 ml) had
      a mean value for the estimations of 885ml (95% CI 771-999 ml). Conversely, the
      clothing simulation (500 ml) emphasized over-estimation, with a mean value for
      the estimations of 1,253 ml (95% CI 1,093-1,414 ml). There was no relationship
      between increased accuracy and clinical experience, exposure, educational
      qualifications, or age of students. CONCLUSIONS: External blood loss estimation
      by undergraduate paramedic students generally is too inaccurate to be of any
      clinical benefit. Particularly, absorbent and impermeable surfaces precipitated
      inaccuracies by undergraduate paramedic students.

PMID- 18709939
TI  - The 2003 Bam earthquake: overview of first aid and transport of victims.
AB  - INTRODUCTION: In December 2003, the residents of Bam, Iran experienced an
      earthquake that measured 6.6 on the Richter scale and destroyed more than 90% of
      the city. PROBLEM: The purpose of this study was to assess the status of the
      rescue, evacuation, and transportation of the casualties during the early stages
      following the earthquake. METHODS: A cross-sectional study of 185 casualties who
      were transferred to and hospitalized in the university hospital during the first
      week period following the earthquake was conducted. Information regarding
      different places of settlement after being removed from the rubble, initial
      medical care, and the means of transportation was obtained by reviewing medical
      records and interviewing the victims. RESULTS: The mean value of the duration of
      times taken for the first rescuers to reach the scene and remove the casualties
      from the rubble was 1.7 +/- 2.7 and 0.9 +/- 1.1 hours, respectively. Sixty-nine
      (37.7%) of the patients stayed within the area immediately surrounding their home
      for average times of 8 +/- 10 hours. The majority of casualties (57.6%) were
      transferred manually to a first place of settlement; 45.8% were taken to a second
      place of settlement using blankets. Of the patients studied, 159 (85.9%) did not
      receive any basic medical care at the first place and intravenous fluid therapy
      was the most common treatment provided for 24 (13%) patients at the second place
      of settlement. Patients received medical care at the first place of settlement
      for a mean time of 16.8 +/- 13.5 hours after escaping the rubble. CONCLUSIONS:
      These findings indicate that the emergency medical service system in Bam was
      destroyed and not able to respond adequately. In order to reduce the negative
      effects of such disasters in the future, there is an essential need for a
      comprehensive disaster management plan and improvement of hospital structures,
      healthcare facilities, and communication between the different governmental
      departments for better coordination and planning.

PMID- 18709940
TI  - Treatment management in disaster: a review of the Bam earthquake experience.
AB  - In the early morning of 26 December 2003, Bam, an old city in southeastern Iran,
      was devastated by an earthquake measuring 6.6 on the Richter scale. Managing such
      situations always brings about many problems. In the case of the Bam Earthquake,
      two of the most serious problems were rescue operations and provision of
      appropriate treatment within a short period of time. By conducting an opinion
      survey, this study aims to assess different aspects of treatment management,
      including personnel, the transfer of the injured, equipment, facilities, and
      treatment planning. Questionnaires containing open questions regarding the
      management of treatment at five levels were prepared. Those engaged in treatment
      at different levels, including physicians, treatment workers, military personnel,
      and executives, were questioned. Several problems were revealed concerning the
      composition of the treatment forces dispatched, into the region, distribution of
      the tasks among treatment workers, and the transferring of equipment, and
      facilities. The most significant problem was a lack of coordination among the
      organizations responsible for the management of the disaster. A comprehensive
      disaster plan is required if prompt handling of mass-casualty incidents and
      coordinating the management of such large-scale disasters are to be ensured.

PMID- 18709941
TI  - Leadership as a component of crowd control in a hospital dealing with a mass
      casualty incident: lessons learned from the October 2000 riots in Nazareth.
AB  - INTRODUCTION: Crowd control is essential to the handling of mass-casualty
      incidents (MCIs). This is the task of the police at the site of the incident. For
      a hospital, responsibility falls on its security forces, with the police assuming
      an auxiliary role. Crowd control is difficult, especially when the casualties are
      due to riots involving clashes between rioters and police. This study uses data
      regarding the October 2000 riots in Nazareth to draw lessons about the
      determinants of crowd control on the scene and in hospitals. METHODS: Data
      collected from formal debriefings were processed to identify the specifics of a
      MCI due to massive riots. The transport of patients to the hospital and the
      behavior of their families were considered. The actions taken by the Hospital
      Manager to control crowds on the hospital premises also were analyzed. RESULTS:
      During 10 days of riots (01-10 October 2000), 160 casualties, including 10
      severely wounded, were evacuated to the Nazareth Italian Hospital. The Nazareth
      English Hospital received 132 injured patients, including one critically wounded,
      nine severely wounded, 26 moderately injured, and 96 mildly injured. All victims
      were evacuated from the scene by private vehicles and were accompanied by
      numerous family members. This obstructed access to hospitals and hampered the
      care of the casualties in the emergency department. The hospital staff was unable
      to perform triage at the emergency department's entrance and to assign the
      wounded to immediate treatment areas or waiting areas. All of the wounded were
      taken by their families directly into the "immediate care"location where a great
      effort was made to prioritize the severely injured. In order to control the
      events, the hospital's managers enlisted prominent individuals within the crowds
      to aid with control. At one point, the mayor was enlisted to successfully achieve
      crowd control. CONCLUSIONS: During riots, city, community, and even makeshift
      leaders within a crowd can play a pivotal role in helping hospital management
      control crowds. It may be advisable to train medical teams and hospital
      management to recognize potential leaders, and gain their cooperation in such an
      event. To optimize such cooperation, community leaders also should be acquainted
      with the roles of public health agencies and emergency services systems.

PMID- 18709942
TI  - Hospital strategic preparedness planning: the new imperative.
AB  - Strategic preparedness planning is an important new imperative for many
      hospitals. Strategic preparedness planning goes beyond traditional product/market
      strategic planning by focusing on disaster prevention, containment, and response
      roles. Hospitals, because of their unique mission, size, complexity, the types of
      materials they handle, and the types of patients they encounter, are especially
      vulnerable to natural and human-initiated disasters. In addition, when disasters
      occur, hospitals must develop well-conceived first responder (receiver)
      strategies. This paper argues the case for strategic preparedness planning for
      hospitals and proposes a process for this relatively new and much needed type of
      planning.

PMID- 18709943
TI  - Principles of disaster planning for the pediatric population.
AB  - Unique physiological, developmental, and psychological attributes of children
      make them one of the more vulnerable populations during mass-casualty incidents.
      Because of their distinctive vulnerabilities, it is crucial that pediatric needs
      are incorporated into every stage of disaster planning. Individuals, families,
      and communities can help mitigate the effects of disasters on pediatric
      populations through ongoing awareness and preventive practices. Mitigation
      efforts also can be achieved through education and training of the healthcare
      workforce. Preparedness activities include gaining Emergency Medical Services for
      Children Pediatric Facility Recognition, conducting pediatric disaster drills,
      improving pediatric surge capacity, and ensuring that the needs of children are
      incorporated into all levels of disaster plans. Pediatric response can be
      improved in a number of ways, including: (1) enhanced pediatric disaster
      expertise; (2) altered decontamination protocols that reflect pediatric needs;
      and (3) minimized parent-child separation. Recovery efforts at the pediatric
      level include promoting specific mental health therapies for children and
      incorporating children into disaster relief and recovery efforts. Improving
      pediatric emergency care needs should be at the forefront of every disaster
      planner's agenda.

PMID- 18709944
TI  - Mental health problems following the 2005 earthquake in Kashmir: findings of
      community-run clinics.
AB  - INTRODUCTION: Events such as earthquakes are followed by significant psychiatric
      morbidity due to the enormous damage caused to life, health, property, and other
      resources in the affected area. In October 2005, a devastating earthquake
      occurred in Kashmir in India. A team of mental health professionals visited the
      earthquake stricken area to provide mental health services five weeks after of
      the event. METHODS: The team conducted clinics at > 30 sites in different
      villages in the area. This paper describes the mental health problems encountered
      in those communities. RESULTS: All patients seen in the clinics had their houses
      destroyed by the earthquake. Nearly one-fourth had suffered serious physical
      injuries and 12% had lost one of their family members. Common psychiatric
      diagnoses included adjustment disorders (39.6%), depressive episode (22.6%), and
      other stress disorders (21.8%). Only 10 (3.3%) patients were found to suffer from
      posttraumatic stress disorder (PTSD), though PTSD-like symptoms were reported by
      more than two-thirds of the patients. CONCLUSIONS: Adjustment disorders,
      depression, other stress reactions, and PTSD-like symptoms were the common mental
      health problems five to six weeks following an earthquake.

PMID- 18709945
TI  - Radiological terrorism scenarios.

PMID- 18709946
TI  - Emergency preparedness for the health sector and communities--challenges and the
      way forward. WHO Expert Consultation. Geneva, 15-17 February 2006.
AB  - In accordance with the World Health Assembly Resolution 58.1, the World Health
      Organization (WHO) convened an Expert Consultation in Geneva, Switzerland from 15
      17 February 2006 to discuss and provide recommendations for enhancing emergency
      preparedness and capacity building at the community, country, regional, and
      global levels. The consultation included experts and representatives of non
      governmental and inter-governmental organizations. Recommendations included a set
      of operational objectives and strategies for achieving them. It was recognized
      that emergency preparedness is part of development and that crises occur at the
      community level. The recommendations, therefore, were focused at the community
      and country levels and outlined processes by which WHO could assist countries in
      augmenting their abilities to cope with health emergencies. This document
      provides a detailed discussion of the issues addressed, the conclusions reached,
      and recommendations based on the conclusions.

PMID- 18709947
TI  - [Expression of rhodopsin for experimental myopia of form-deprivation and defocus
      in guinea pig].
AB  - PURPOSE: To investigate the rhodopsin expression in form-deprived and defocus
      myopia in guinea pig and study the relationship between the rhodopsin expression
      and experimental myopia. METHODS: Fourty guinea pigs were randomized into the
      form-deprived group and the defocus group (n = 20). Guinea pigs in the form
      deprived group wore a diffused (rigid glass-permeable contact lens (RGP) on one
      eye since one week after birth. Those in defocus group wore a -4 D RGP on one
      eye. The contralateral eyes were left as control. Refraction, axial length and
      depth of vitreous cavity were measured after 1 and 2 weeks respectively. Retina
      were dissected at 10-12 o'clock in the morning. The level of rhodopsin and its
      mRNA were observed through Western-blot and real-time PCR respectively. RESULT:
      There is no difference between form-deprived group, defocus group and control
      groups (except refraction in form-deprived group). One week later, there is no
      difference between the form-deprived group, the defocus group and the control
      groups (except refraction in form-deprived group). Two weeks later, eyes in the
      form-deprived group and the defocus group became myopic. Its axial length
      lengthened and depth of vitreous cavity appeared deep. The form-deprived groups
      showed an increased expression of rhodopsin and its mRNA compared to the control
      groups. There is no difference between the defocus group and the control groups.
      CONCLUSION: Expression of rhodopsin might involve formation of form-deprived
      myopia, but has less influence on defocus myopia.

PMID- 18709948
TI  - [Vitreous levels of stromal cell-derived factor-1 and vascular endothelial growth
      factor in diabetic retinopathy].
AB  - PURPOSE: To investigate the levels of stromal cell-derived factor-1 (SDF-1) and
      vascular endothelial growth factor (VEGF) in the vitreous of patients with
      proliferative diabetic retinopathy. METHODS: The levels of SDF-1 and VEGF in the
      vitreous of 30 eyes of 30 patients with proliferative diabetic retinopathy (PDR)
      and 12 eyes of 12 patients with idiopathic macular hole (MH) were measured by
      enzyme-linked immunosorbent assay. Vitreous fluid samples were obtained by
      vitrectomy. RESULTS: The vitreous concentration of VEGF was significantly higher
      in eyes with PDR (2,865.87 +/- 387.85 pg/ml) than in eyes with idiopathic macular
      hole (142.42 +/- 21.03 pg/ml, P < 0.0001). The vitreous level of SDF-1 was also
      significantly higher in eyes with PDR (298.40 +/- 24.57 pg/ml) than in eyes with
      idiopathic macular hole (86.91 +/- 15.89 pg/ml, P < 0.0001). The vitreous
      concentration of SDF-1 correlated significantly with that of VEGF in eyes with
      PDR ([correlation coefficient] r = 0.62, P < 0.001). CONCLUSION: Vitreous levels
      of both SDF-1 and VEGF in patients with PDR are significantly higher than those
      of nondiabetic patients. SDF-1 may be correlated with VEGF in angiogenesis in
      PDR.

PMID- 18709949
TI  - [A study on effect of bFGF, EGF and NGF on growth of cultured human corneal
      endothelial cells].
AB  - PURPOSE: To investigate effect of bFGF, EGF and NGF on growth of cultured human
      corneal endothelial cells. METHODS: Cultured human corneal endothelial cells were
      seeded into individual wells of 96-well tissue culture plate with the same
      culture media containing separately bFGF, EGF or NGF with a serial of
      concentrations of 0 ng/ml, 1 ng/ml, 3 ng/ml, 10 ng/ml, 30 ng/ml and 100 ng/ml and
      then cultured for 5 days. Then MTT method was used to detect the growth of the
      cells. RESULTS: The averaged OD values of the cell wells containing bFGF with a
      serial of concentrations of 0 ng/ml, 1 ng/ml, 3 ng/ml, 10 ng/ml, 30 ng/ml and 100
      ng/ml were 0.224 +/- 0.045, 0.239 +/- 0.040, 0.262 +/- 0.0342, 0.278 +/- 0.0319,
      0.281 +/- 0.0324, 0.260 +/- 0.0310. The averaged OD values of EGF group and NGF
      group were separately 0.228 +/- 0.0304, 0.245 +/- 0.0418, 0.267 +/- 0.0454, 0.275
      +/- 0.0347, 0.271 +/- 0.0449, 0.250 +/- 0.0253 and 0.216 +/- 0.0187, 0.228 +/-
      0.0226, 0.231 +/- 0.0225, 0.242 +/- 0.0279, 0.245 +/- 0.0294, 0.247 +/- 0.0349.
      CONCLUSION: bGFG can promote the growth of human corneal endothelial cells in a
      dose dependent manner while with concentration lower than 30 ng/ml. bFGF with
      concentration that is higher than 100 ng/ml will weaken this effect. EGF can also
      promote proliferation of human corneal endothelial cells demonstrating a linear
      dose dependent effect when its concentration is lower than 10 ng/ml and this
      effect decreased when its concentration was higher than 30 ng/ml. NGF showed no
      effect on the growth of human cornea endothelial cells in this study.

PMID- 18709950
TI  - [Effect of TGF-beta1 on expression of integrin beta1 following corneal alkali
      burns in rabbits].
AB  - PURPOSE: To observe the effect of TGF-beta1 applied topically to the alkali
      injured rabbit eye on corneal epithelial wound healing and expression of integrin
      beta1 and its therapeutic action on corneal alkali burns. METHODS: Alkali burn
      was produced in 60 corneas from 30 rabbits. Two groups were randomly divided. One
      group was treated with TGF-beta1 solution (200 ng/ml) topically 3 times one day
      within the first 7 days, the other group was treated with phosphate-buffered
      saline (PBS) solution. The injured eyes were photographed after the fluorescence
      staining with a digital camera and the pictures were analyzed with computer-aided
      picture analysis system to calculate the rate of corneal epithelial healing. The
      expression of integrin beta1 was investigated in the point 6 h, 1 d, 3 d, 7 d, 14
      d after the injury by means of immunohistochemical analysis. RESULTS: On the 4th,
      10th, 11th, 12th and 14th days after the burning,the rate of corneal epithelial
      healing of TGF-beta1 groups was markedly higher than that of the PBS group (P <
      0.05). The expression of integrin beta1 in the cornea epithelial cells gradually
      increased during the wound healing. On the 7th and 14th days after the burning,
      the expression of integrin beta1 in the cornea epithelial cells of TGF-beta1
      group was remarkably higher than that of the PBS group (P < 0.05). CONCLUSIONS:
      TGF-beta1 could up-regulate integrin beta1 in vivo corneal alkali burn model,
      which could stimulate the cornea epithelial cells to migrate and adhere to the
      cornea stroma, that can reduce the cases of the epithelial cells'detachment from
      the cornea stroma and sustain the corneal reepithelization.

PMID- 18709951
TI  - [Different concentrations of clarithromycin ophthalmic gel for rabbits corneal
      ulcers induced by Staphylococcus aureus].
AB  - PURPOSE: To screen proper concentration of clarithromycin ophthalmic gel by
      observing the efficacy of different concentrations of clarithromycin ophthalmic
      gel for treating staphylococcal corneal ulcers. METHODS: Corneal ulcer was
      induced in the right eye of 40 rabbits, 3.0 x 10(9) CFU/ml staphylococcus aureus
      suspension was injected midstromally into the central corneal. These rabbits were
      divided randomly into 5 groups, each group received respectively topical blank
      matrix, clarithromycin ophthalmic gel 0.1%, clarithromycin ophthalmic gel 0.25%,
      levofloxacin ophthalmic gel, clarithromycin ophthalmic gel 0.25% and recombinant
      bovine basic fibroblast growth factor (Rb-bFGF), 4 times every day, 2 drops each
      time. The eyes were examined respectively with the slit lamp before treatment
      (day 0), on day 3, day 5, day 7, day 10, day 14 to observe the progression of
      corneal ulceration, including the area of the corneal ulcer and mark of
      keratitis. RESULTS: Under the same way of giving medicine, experimental corneal
      ulcer studies showed a statistically significant decrease in all treatment groups
      on measurements of the area of the corneal ulcer and mark of keratitis (P <
      0.05), and clarithromycin ophthalmic gel 0.25% had a better action than
      clarithromycin ophthalmic gel 0.1% against staphylococcus aureus corneal ulcer.
      CONCLUSION: Clarithromycin ophthalmic gel 0.25% was proved to be an effective
      ocular medication for the therapy of gram-positive bacterial corneal ulcer.

PMID- 18709952
TI  - [Coverslip assisted primary tissue culture for human lens epithelial cells in
      vitro].
AB  - PURPOSE: To set up an easy procedure of tissue culture for human lens epithelial
      cells in vitro and to observe the biological characteristics. METHODS: Capsules
      from embryo of 20 weeks, eye bank of Zhongshan Ophthalmic Centre and patients
      with cataract were spread on culture utensil. 10 microL of 10% DMEM medium was
      added and a piece of coverslip was lay to prevent crimp. Then the capsules were
      cultured under 37 degrees C after adding enough medium. Capsules from the same
      source were cultured by traditional tissue culture method. Expressions of 13
      crystallin between primary tissue culture cells and SRA01/04 cell line were
      compared by western blotting. RESULTS: With coverslip assisted, the cells could
      be observed proliferated and migrated from the edge of embryo capsule 2 days
      later, and for capsules from eye bank and age-related cataract patients, the
      interval time was 3 to 4 days. By traditional tissue culture method, the interval
      time of embryo capsule was 3 to 4 days, and for capsules from eye bank and age
      related cataract patients, the interval time was the same. And capsules floated
      sometimes. CONCLUSIONS: By coverslip assisted primary tissue culture human lens
      epithelial cells could grow faster and easier, and the method is worthy to be
      spread in research of lens diseases.

PMID- 18709953
TI  - [Effect of tear film changes on the intraocular pressure measurement by Goldmann
      applanation tonometer].
AB  - PURPOSE: To explore the effect of tear film changes on the intraocular pressure
      (IOP) measurement by Goldmann applanation tonometer. METHODS: Sixty-eight normal
      subjects were randomly divided into two groups (Group A and B), 34 in each group.
      One eye of each subject by random selection was given Dextran (in Group A) and
      Viscoat (in Group B), respectively. And the fellow eyes were used as controls.
      IOP was measured in all subjects twice using Goldmann applanation tonometer. And
      the difference between first and second measurements was compared. RESULT: In the
      control eyes of Group A, the average IOP of first and second measurements were
      (14.44 +/- 2.68) mmHg (1 mmHg = 0.133 KPa) and (14.47 +/- 2.69) mmHg, there was
      no difference between the two measurements (t = -0.329, P = 0.744). In eyes given
      Dextran, the average IOP of two measurements were (14.41 +/- 2.63) mmHg and
      (12.94 +/- 2.59) mmHg, there was significant difference between the two
      measurements (t = 13.949, P = 0.000). In control eyes of Group B, the average IOP
      of first and second measurements were (14.53 +/- 3.13) mmHg and (11.18 +/- 3.07)
      mmHg, and there was no difference between the two measurements (t = -0.466, P =
      0.644). In eyes given Viscoat, the average IOP of two measurements were (14.53 +/
      3.13) mmHg and (11.18 +/- 3.07) mmHg, and there was significant difference
      between the two measurements (t = 22.126, P = 0.000). After being given Dextran
      or Viscoat, the IOP values decreased consistently in both Group A and Group B.
      CONCLUSIONS: The change of tear film components can affect IOP values by Goldmann
      applanation tonometer.

PMID- 18709954
TI  - [Comparison of different power-density krypton laser combined with Nd:YAG laser
      peripheral iridotomy].
AB  - PURPOSE: To compare the influence of krypton laser with different power densities
      combined with Nd:YAG laser peripheral iridotomy (LPI) on the intraocular
      pressure, blood-aqueous barrier and inflammatory of anterior chamber as well as
      the therapeutic effect. METHODS: Using a laser flare cell meter and Goldmann
      tonometer, the level of aqueous protein, the number of cells in the anterior
      chamber and intraocular pressure of 31 patients (62 eyes) who underwent krypton
      laser with different power densities combined with Nd:YAG laser peripheral
      iridotomy were examined and recorded preoperatively and postoperatively. RESULTS:
      The mean preoperative and 1-hour, 3-day, 7-day, 1-month postoperative intraocular
      pressure (IOP) of the high power-density group were (15.68 +/- 2.41), (27.13 +/-
      3.48), (20.97 +/- 5.27), (16.35 +/- 1.14) and (15.06 +/- 2.02) mmHg, while those
      of the low were (15.35 +/- 1.78), (22.77 +/- 3.26), (16.26 +/- 2.41), (15.68 +/-
      2.06) and (15.06 +/- 1.36) mmHg. The mean preoperative and 3-day, 7-day, 1-month
      postoperative flare intensity of the high power-density group were (4.65 +/-
      1.50), (10.41 +/- 2.47), (7.31 +/- 2.31) and (6.15 +/- 2.16) pc/ms, while those
      of the low were (4.45 +/- 1.19), (6.47 +/- 1.11), (4.81 +/- 0.55) and (4.98 +/-
      1.48) pc/ms. The number of aqueous cells of the high was (0.47 +/- 0.42), (36.22
      +/- 9.16), (18.54 +/- 3.60) and (6.29 +/- 0.98), while that of the low was (0.58
      +/- 0.52), (24.73 +/- 6.09), (10.61 +/- 1.70) and (2.96 +/- 1.35). The mean 1
      hour and 3-day postoperative IOP of the high was higher than that of the low.
      Both the mean flare intensity and the mean number of aqueous cells of the high
      power-density group were higher than those of the low. The differences were of
      statistical significance (P < 0.05). The mean flare intensity of the high power
      density group in the 1-month postoperative follow-up was still higher than the
      baseline. The mean number of aqueous cells of both the high and the low power
      density groups in the 1-month postoperative follow-up was still higher than the
      baseline. During 1-month follow-up, no obvious visual damage, diffuse corneal
      endothelial burns or corneal decompensation, lens injury and closure of the
      peripheral iris incision were observed. CONCLUSION: When krypton laser combined
      with Nd:YAG laser peripheral iridotomy is under consideration, relatively low
      power-density krypton laser is recommended because it can achieve the similar
      therapeutic effects as high power-density krypton laser but leads to less
      complications and a briefer recovery. More follow-ups are needed after LPI,
      because the number of aqueous cells in 1-month follow-up was still abnormal.

PMID- 18709955
TI  - [Comparative analysis of the formation of functional filtration bleb in different
      incision of conjunctiva flap after trabeculectomy].
AB  - PURPOSE: To assess the success rate of the formation of functional filtration
      bleb in eyes undergoing different incision of conjunctiva flap after
      trabeculectomy. METHODS: To study the formation of functional filtration bleb
      after trabeculectomy, the result of trabeculectomy with the limbus based
      conjunctival flap in 165 eyes and the fornix based conjunctival flap in 207 eyes
      (372 eyes in 372 cases with primary glaucoma in total) was compared. RESULTS: All
      patients were observed after trabeculectomy in 1 week, but only 127 eyes were
      followed up in 3 months. In patients with trabeculectomy using the limbus based
      conjunctival flap, the success rate of the formation of the filtration bleb was
      83.03% in 1 week and 78.69% in three months postoperatively, while in those using
      the fornix based conjunctival flap, the success rate was 55.07% in 1 week and
      53.03% in 3 months. There was significant difference between the two groups in
      terms of the success rate of the formation of the filtration bleb. CONCLUSIONS:
      The result showed that limbus based conjunctival flap was especially effective
      and had better postoperative intraocular pressure decline.

PMID- 18709956
TI  - [Fresh versus preserved amniotic membrane transplantation for conjunctival
      surface reconstruction].
AB  - PURPOSE: To compare the effect of fresh versus preserved amniotic membrane
      transplantation for conjunctival surface reconstruction after symblepharon lysis
      and analyze the associated factors. METHODS: Fifty-one consecutive cases (55
      eyes) with symblepharon at different degree due to eye burns or Stevens-Johnson
      syndrome were accepted lysis of symblepharon and amniotic membrane
      transplantation. Twenty-two eyes of them were performed with fresh amnion grafts,
      the others (33 eyes) with preserved human amniotic membrane. Eleven eyes were
      performed within 1 year and forty eyes in 1 to 8 years (mean value, 2.0 +/- 0.7
      years) after eye burns. RESULTS: The follow-up time varied from 12 to 32 months
      (mean value, 19.3 +/- 4.1 months). Fifty-six point four percent (31/55) eyes got
      enough deep conjunctival fornix and resolution of eye movement restrict. Sixteen
      percent of them (9/55) recurred less symblepharon and remained slightly eye
      movement restrict. Fifteen-five eyes of them (27.3%) recurred moderate
      symblepharon. The effects of surgery were similar between fresh and preserved AMT
      (chi2 = 0.466, P = 0.797). The effects of AMT for those patients with
      symblepharon at different degree had significant difference statistically (fresh
      amnions, chi2 = 27.995, P = 0.000; preserved amnions, chi2 = 33.610, P = 0.000).
      The same results were observed between those patients who were performed in
      different time periods after eye burns (chi2 = 4.243, P = 0.039). CONCLUSION:
      Fresh amnion has the same effect as preserved one for conjunctival surface
      reconstruction. The degree of symblepharon and the surgical environment of the
      ocular surface in the affected eye before surgery will influence the results of
      amniotic membrane transplantation for conjunctival surface reconstruction.

PMID- 18709957
TI  - [Clinical analysis for retinal detachment after cataract surgery in high myopic
      eyes].
AB  - AIM: To analyze the clinical characteristics, incidence and risk of retinal
      detachment (RD) after cataract surgery and posterior chamber intraocular lens
      implantation in high myopic patients. METHODS: The medical records of 146 high
      myopic patients (232 eyes) who underwent cataract surgery and posterior chamber
      intraocular lens implantation were studied retrospectively. The development of RD
      was followed up over a 3-year period, and its characteristics were determined.
      All of the eyes received a comprehensive ophthalmological examination, including
      best-corrected visual acuity measurements, a dilated fundus examination and axial
      length measured by A-scan ultrasonography. RESULTS: RD developed in 15 eyes of 15
      patients. All the 15 eyes needed vitreo-retinal surgery. The mean interval
      between cataract surgery and the development of RD was 10 +/- 9 months (range 0.5
      32 months). The visual results of the eyes after anatomical successful vitreo
      retinal surgery ranged from finger count/10 cm to 0.06. 80% (12/15) of the eyes
      had a worse vision after the surgery than that before cataract surgery. Posterior
      capsular tear were associated significantly with RD (P < 0.01). Approximately 60%
      (9/15) of retinal detachment was attributable to posterior capsule tear during
      cataract surgery. CONCLUSION: Incidence of RD in high myopic patients after
      cataract surgery was 6.4%. RD was the potentially serious complication and tended
      to develop more frequently in eyes with posterior capsular rupture during
      cataract surgery. It is crucial to examine retinal status after cataract surgery
      and to have a close follow-up to prevent retinal complications, especially for
      patients with posterior capsular disruption.

PMID- 18709958
TI  - [Repeatability of ETDRS visual acuity measurement in children].
AB  - PURPOSE: To evaluate repeatability of the ETDRS log MAR visual acuity measurement
      in children and the relative influence factors. METHODS: The children (n = 348)
      with visual acuity less than 0.5 (equal to 0.3 log unit) in either eye, or one
      tenth in children with normal visual acuity were chosen to do repeatable
      uncorrected VA measurement with Bland-Altman analysis and Kappa analysis using
      ETDRS acuity chart. RESULTS: The mean difference of visual acuity was 0.004 log
      +/- 0.07. There was a significant repeatability (k = 0.71) between two visual
      acuity examination. There were significant consistent results both on male and
      female patients (P = 0.845). A significant relationship was found between age and
      VA repeatability (P = 0.019). The VA repeatability could also be influenced by
      refractive error (P = 0.000). The acuity measurement in children with emmetropia
      (k = 0.82) had a higher repeatability than in the children with myopia (k =
      0.66). CONCLUSIONS: The ETDRS visual acuity chart can provide a repeatable
      measure of visual acuity in children. It is recommended for clinic examination of
      children.

PMID- 18709959
TI  - [Correlation analysis of pupil light reflex and visual functions after unilateral
      ocular contusion].
AB  - SUBJECTS AND OBJECTIVE: To measure the quantitative pupil light reflex after
      unilateral ocular contusion, analyze the correlation of pupil light reflex and
      other tests of visual function. METHODS: The pupil light reflex in 26 patients
      who suffered unilateral ocular contusion was tested by infrared video
      pupillography, psychophysical and electrophysiological tests including visual
      acuity, visual field, and visual evoked potentials were also tested. Pupil area,
      the latency and amplitude of pupil light reflex were recorded. RESULTS: The
      correlation of the ratio of pupil light reflex amplitude and the differences of
      visual acuity between 2 eyes in 26 contusion patients was statistically
      significant. The correlation coefficient r was -0.648. There were significant
      correlation between amplitude of pupil light reflex and median defect of visual
      field. The correlation coefficients r were 0.5 and 0.535. The significant
      correlations were found in the ratio of amplitudes between pupil light reflex and
      visual evoked potentials. Multiple linear regression analysis showed combining
      pupil light reflex amplitude and visual evoked potential amplitude could elevate
      the possibility of predicting visual acuity. CONCLUSION: Pupil light reflex
      amplitude measurement is superior to other pupil measurements for reflection of
      the changes of visual function after ocular contusion. The correlations of pupil
      light reflex amplitude and visual acuity, visual field, visual evoked potential
      are significant in the ocular contusion patient. Pupil light reflex combined with
      visual evoked potential could elevate the possibility of predicting visual
      function precisely after ocular contusion.

PMID- 18709960
TI  - [Fundus analysis of autofluorescence of stale fundus haemorrhage in indocyanine
      green angiography].
AB  - OBJECTIVE: To investigate the autofluorescence of stale fundus haemorrhage in age
      related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV)
      with indocyanine green angiography (ICGA). METHODS: The color photographs and
      ICGA were performed in 36 eyes of 36 cases of exudative AMD or PCV with stale
      fundus haemorrhage. All of the cases were examined by funduscopy and fundus
      fluorescein angiography (FFA). RESULTS: Autofluorescence could be observed in all
      of the stale haemorrhage cases. Stale haemorrhage showed grayish color and the
      shapes and sizes of autofluorescence in ICGA were in accordance with those of the
      stale haemorrhage in the color photographs. The boundaries of autofluorescence
      were clear and the intensities were strong. The percentage of choroidal
      neovascularization (CNV) or PCV in or beside stale haemorrhage was significantly
      higher than that outside the stale haemorrhage (27 eyes, 75%). CONCLUSIONS:
      Autofluorescence of stale haemorrhage in ICGA can be mixed up with the high
      fluorescence of CNV and grapes-like polypoidal dilatation. It is helpful to
      compare the color photographs with ICGA and recognize the different ICGA
      characteristics in the assessment of ICGA results in these circumstances.

PMID- 18709961
TI  - [The clinical study of the damage of visual function caused by pituitary tumor].
AB  - PURPOSE: To investigate the clinical manifestation of damage of visual function
      caused by pituitary adenoma. METHODS: Visual acuity, visual field, fundus
      fluorescein angiography (FFA), pattern visual evoked potential (PVEP) and
      examination fundus were performed in 126 cases (252 eyes) of pituitary tumor.
      RESULTS: There was 73.8% (186 eyes) of patients with decreased visual acuity,
      51.6% (130 eyes) with primary optic atrophy, 69.6% (156 eyes) with the defects of
      visual field and 88.9% (160 eyes) with abnormal PVEP. Abnormal ophthalmological
      manifestation was the first diagnostic symptom in 26.2%, and 16.7% was
      misdiagnosed as eye diseases. CONCLUSIONS: Pituitary tumor could cause defection
      of visual function. It is helpful to early diagnosis and timely treatment by
      fully understanding clinical features in the eye with pituitary tumor.

PMID- 18709962
TI  - [Transthyretin Arg-83 mutation in vitreous amyloidosis].
AB  - Vitreous amyloidosis is a rare condition that mainly occurs in Familial
      Amyloidotic Polyneuropathy (FAP). In some cases, it may be the only symptom
      without systemic disorders. One case of familial vitreous amyloidosis was
      reported here, with white, wispy opacities in vitreous cavity in both eyes. Pars
      plana vitrectomy and histopathological examination of the vitreous specimens were
      performed. The vitreous specimens showed typical microscopic features of
      amyloidosis with Congo red stain and non-branching fibrils on a transmission
      electron microscope. Transthyretin (TTR) gene was amplified with DNA isolated
      from the peripheral blood cells. Bi-directional sequencing of exon 3 showed a
      single base-pair substitution, which results in an amino acid substitution at
      position83, glycine to arginine (TTR Arg-83). TTR Arg-83 may be a new pathologic
      mutation in vitreous amyloidosis.

PMID- 18709963
TI  - [A teratoid malignant medulloepithelioma of the optic nerve].
AB  - Medulloepithelioma is a clinically uncommon tumor originated from nervous system,
      often occurred in central nerve system and ciliary body, and malignant
      medulloepithelioma of the optic nerve is far rarer. So far, there has been no
      case report in China. It may be clinically misdiagnosed because it resembles
      glioma at the early stage of the disease. We reported a boy with a tumor in his
      right eye at age of 3.8 years, which was shown by biopsy of the partial tumor
      that there were some obviously heteromorphous neoplastic cells, karyokinesis, and
      moreover, some neoplastic cells differentiated into cartilage cells, gradually
      formed into hyaline cartilage islands and the expressions of NSE and S-100 were
      positive. Teratoid malignant medulloepithelioma of optic nerve was made
      pathologically.

PMID- 18709964
TI  - [A case of papilloedema caused by primary empty sella turcica syndrome].
AB  - PURPOSE: To report a case of papilloedema caused by primary empty sella turcica
      syndrome. METHODS: Retrospectively review the clinical and physical features,
      magnetic resonance imaging records and therapies of a patient with papilloedema
      caused by primary empty sella turcica syndrome. RESULTS: Except for typical
      clinical manifestation of papilloedema, a characteristic magnetic resonance
      imaging (MRI) can be found in a case of papilloedema caused by primary empty
      sella turcica syndrome. These imaging features are that sella turcica expanded,
      the inside of sella turcica was filled with cerebrospinal fluid (CSF) signal,
      pituitary gland was pressed, flattened and near the basis of sella turcica.
      Papilloedema was relieved and acuity of vision improved after surgery.
      CONCLUSIONS: MRI is the preferred imaging technique for patient with papilloedema
      caused by primary empty sella turcica syndrome. If acuity of vision apparently
      decreases, surgery is necessary, and therapeutic effect is excellent.

PMID- 18709965
TI  - [Identification of 23 mycobacterial species by Invader assay with targeting 16S
      rRNA gene and ITS-1 region--comparison with DDH method in clinical isolates].
AB  - PURPOSE AND METHOD: The Invader assay was developed to identify 23 mycobacterial
      species using probes derived from the species-specific region of the 16S rRNA
      gene and the 16S-23S rRNA internal transcribed spacer 1 (ITS-1) region, with
      minor modifications of our previous study. In the present study, we compared the
      identification capability between the Invader assay and DNA-DNA hybridization
      (DDH) method. DDH is commonly used to identify non-tuberculosis mycobacterium in
      Japan and 636 clinical mycobacterial strains cultured on Ogawa slants were
      tested. RESULTS: The Invader assay could identify 615 (96.7%) of the 636 strains.
      The results contained 14 M.lentiflavum, 3 M. parascrofulaceum and 1 M.
      intermedium, which were undetectable with DDH method. On the other hand, DDH
      method could identify 580 (91.2%) strains with duplicate assay. Of 628 strains
      except 8 strains identified as a few species by Invader assay, 551 (87.7%)
      strains were identified as the same species by two methods. Discordant results
      were mainly recognized for the identification of M. gordonae, M. avium, M.
      lentiflavum and M. intracellurare. The results of other methods targeting 16S
      rRNA indicated correctness of the Invader assay. CONCLUSION: These results
      indicate that Invader assay could identify more correctly than DDH method and
      could identify about 97% of clinically important mycobacterium.

PMID- 18709966
TI  - Epidemiological survey of hyperuricemia as an adverse reaction to antituberculous
      therapy with pyrazinamide.
AB  - PURPOSE: Pyrazinamide is an antituberculous drug that is administered as a two
      month course during treatment of pulmonary tuberculosis. Adverse reactions to
      pyrazinamide have been reported to include hyperuricemia. We performed a
      retrospective multicenter epidemiological survey to assess the relationship
      between various patient characteristics and the uric acid level, the changes of
      uric acid during pyrazinamide administration, and the use of medications for uric
      acid control as well as attacks of gout or arthralgia at the onset of
      hyperuricemia. A total of 226 patients who were admitted to four hospitals with
      pulmonary tuberculosis between January and December 2006 and received short-term
      intensive pyrazinamide therapy were studied. RESULTS: There were 172 men and 54
      women with an average age of 59.5 years and an average body mass index of 19.8
      kg/m2. The average serum uric acid concentration before pyrazinamide treatment
      was 4.73 +/- 1.78 mg/dl, while the average uric acid level after pyrazinamide
      treatment was 10.63 +/- 2.67 mg/dl, which was significantly higher than the
      pretreatment level (p<0.0001). During treatment, hyperuricemia (Serum uric acid >
      or = 8 mg/dl) was reported in 84.5% of patients and arthralgia developed in
      4.42%. Although the therapy instituted in 51 patients (22.57%) had to be
      interrupted or discontinued due to liver dysfunction and skin rashes, which were
      probably caused by isoniazid and rifampicin, no patient ceased taking
      pyrazinamide due to an increase of uric acid. Drugs for uric acid control were
      administered to 21 patients (9.29%). Pyrazinamide is an important agent for
      intensive short-term antituberculous therapy. Hyperuricemia due to this drug can
      be managed by observation and does not require interruption of administration.

PMID- 18709967
TI  - [Estimation of the prevalence of tuberculosis infection in the 1950s in Tokyo].
AB  - PURPOSE: We estimated the prevalence of tuberculosis infection in the 1950s in
      the urban area of Tokyo using results of the tuberculin skin test (TST) in
      infants and children. SUBJECT AND METHODS: We analyzed prevalence of tuberculosis
      using the results of the TST in 728 children (5 m.o.-24 m.o.) without BCG
      vaccination in 1954 in Koto Ward, Tokyo. RESULTS: Assuming that the sensitivity
      and specificity of the TST were 95% and 98%, respectively, the prevalence of TB
      was estimated to be 2% (95% C.I., 0.4-4.3%) among 448 infants under 12 m.o. (mean
      age 0.69 y.o.), and 16% (95% C.I., 11.9-21.5%) among 280 children aged 12 m.o.-24
      m.o. (mean age 1.44 y.o.). CONCLUSION: Being different from the current situation
      of tuberculosis, the risk of infection among infants was high in 1950s in Japan,
      therefore, it was considered that the prevalence of tuberculosis infection rose
      rapidly among infants in their early period after birth. Also, the risk of
      infection in urban areas was higher comparing with the average national rate at
      that time.

PMID- 18709968
TI  - [Clustered secondary case rate in 10,088 patients with tuberculosis].
AB  - OBJECTIVES: To elucidate characteristics in clustered secondary TB patients
      transmitted from culture positive pulmonary TB patients. SUBJECTS AND METHODS:
      The subjects of this retrospective study were 10,088 TB patients registered in
      Aichi Prefecture between 1989 and 2003. Pulmonary TB was found in 8,629 patients,
      and 1,459 had extra-pulmonary TB. Bacteriological examination revealed sputum
      smear-positive (SPBP) in 3,332, sputum smear-negative bacillus-culture-positive
      (SNBP) in 2,139, and smear-negative bacillus-culture-negative (SNBN) in 3,158.
      All registration files were reviewed to identify epidemiological links of
      patients. When linked patients with an interval of the dates of registration of
      less than 10 years were found, the first case was considered as the index case,
      and the other patients were regarded as secondary cases. A clustered secondary
      case rate (CSR) for a category of patients was defined as follows; CSR=NCS/NA,
      where NA: number of TB patients in a category A, and NCS: number of secondary
      cases in category A. A cluster rate for a category of bacillary pulmonary
      patients was defined as follows; Cluster rate= (NIC+NCS)/ NA, where NA: number of
      TB patients in a category A, NIC: number of index cases in category A, and NCS:
      number of secondary cases in category A. RESULTS: A total of 417 patients were
      considered as clustered secondary cases, and the CSR was 4.1% in total. The CSRs
      were 3.5% for the SPBP patients, 3.8% for the SNBP patients, 5.4% for the SNBN
      patients, and 3.4% for the extra-pulmonary patients. The CSR in SNBN patients was
      significantly higher than the SPBP patients (p<0.001). The significant
      differences in the CSRs were found between the SNBN patients and the SNBP
      patients (p<0.01), as well as between the SNBN patients and the extra-pulmonary
      patients (p< 0.01). The CSRs were 42.5% in patients aged 0-9, 30.3% in those aged
      10-19, 11.2% in those aged 20-29, 7.4% in those aged 30-39, 4.6% in those aged 40
      49, 3.2% in those aged 50-59, 2.4% in those aged 60-69, 1.8% in those aged 70-79,
      1.3% in those aged 80-89, and 0.6% in those aged 90-99. There were significant
      differences in the CSRs between those aged 10-19 and those aged 20-29 (p< 0.001),
      between those aged 20-29 and those aged 30-39 (p<0.05), and between those aged 30
      39 and those aged 40-49 (p< 0.05). The male patients showed significantly lower
      CSR than female patients (2.9% vs 6.3%, p<0.001). The cluster rate for the 5,471
      bacillary patients was 8.8%. The cluster rates were significantly different
      between those patients aged 10-19 and those aged 20-29 (37.1% vs 21.1%, p<0.001),
      as well as between those aged 40-49 and those aged 50-59 (16.4% vs 8.5%,
      p<0.001). CONCLUSION: These findings suggest that the CSR is closely related with
      patient's age, gender, and bacillary findings, and that the CSR is significantly
      high in young, female, and SNBN patients.

PMID- 18709969
TI  - [A case of multi-drug resistant pulmonary tuberculosis after administration of
      standard anti-tuberculosis treatment for two times].
AB  - We reported a case in which multi-drug resistant tuberculosis was recognized
      after two courses of anti-tuberculosis treatment. A 41-year-old woman who had
      received two courses of anti-tuberculosis treatment for pulmonary tuberculosis
      was admitted to our hospital due to productive cough, high fever and positive
      sputum smear showing acid fast bacillus. In the past treatment, drug
      susceptibility was unknown because of culture-negative TB. Chest radiograph
      showed atelectasis of the right upper lobe. The pathological examination of
      surgically resected lung specimen revealed that atelectasis was formed by a
      granulation tissue with caseous necrosis progressed to the bronchus wall. We
      examined cultures three times using both solid and liquid media. Liquid culture
      of the first time specimen was positive for Mycobacterium tuberculosis after six
      weeks and multi-drug resistant tuberculosis was recognized on drug susceptibility
      test. Thereafter she was treated with KM, LVFX, PZA and PAS, and maintained
      sputum smear negative for 7 months after treatment. Physicians must consider
      possibility of MDR-TB despite findings showing smear-positive and culture
      negative TB.

PMID- 18709971
TI  - [The International Standards for Tuberculosis Care (ISTC): what is the importance
      for Japan?].
AB  - In 2005, the World Health Assembly resolved that all Member States should ensure
      that all persons with tuberculosis (TB) "have access to the universal standard of
      care based on proper diagnosis, treatment and reporting consistent with the DOTS
      strategy..." The purpose of the International Standards for Tuberculosis Care
      (ISTC) is to define the widely accepted level of care of persons either suspected
      of, or diagnosed with, TB by all health practitioners, especially those in the
      private sector, who often lack guidance and systematic evaluation of outcomes
      provided by government programs. Since their publication in 2006 on World TB Day,
      the standards have been endorsed by the major international health organizations
      as well as many country-level professional societies. The intention is to
      complement local and national control polices consistent with those of the World
      Health Organization: they are not intended to replace local guidelines, but are
      written to accommodate local differences in practice. The ISTC comprise seventeen
      evidence-based standards on tuberculosis diagnosis and treatment, as well as the
      responsibility of the public health sector. These are based on the basic
      principles of TB care: prompt and accurate diagnosis, standardized treatment
      regimens of proven efficacy, appropriate treatment support and supervision,
      monitoring of response to treatment and the carrying out of essential public
      health responsibilities. The relevance of the ISTC to the Japanese context is
      highlighted, in terms of when persons should be suspected of TB; the appropriate
      diagnostic modalities, including the use of chest radiographs; the advantages of
      fixed dose combinations; the importance of follow-up laboratory tests to document
      response to treatment, the importance of recordkeeping and reporting to public
      health authorities, the value of HIV testing of TB patients and the use of anti
      retrovirals for those dually infected; and the assessment of drug resistance and
      the appropriate treatment of multidrug-resistant tuberculosis. Finally, some
      proposals were made on the way forward for Japan.

PMID- 18709970
TI  - [A case of miliary tuberculosis with interstitial nephritis due to re
      administration of rifampicin treated successfully with steroid].
AB  - A 26-year-old man was admitted to a hospital complaing of continuous high fever
      and abdominal swelling. As his sputum and ascites culture was positive for acid
      fast bacilli and PCR-TB, he was diagnosed as miliary tuberculosis, tuberculous
      with pleuritis and peritonitis, and transferrd to our hospital. After initiation
      of treatment with isoniazid, rifampicin (RFP), ethambutol, and pyrazinamide, RFP
      was suspended because of direct-reacting hyperbilirubinemia. As the liver
      function recovered after discontinuation of RFP, low dose of RFP was re
      administrated and renal dysfunction was observed. The renal dysfunction continued
      after discontinuation of suspicious drugs including RFP. As renal biopsy revealed
      interstitial nephritis, prednisolon 20 mg/day was started and renal function
      recovered quickly. From the clinical course and examination, we considered
      interstitial nephritis was due to re-administration of RFP and steroid therapy
      was effective.

PMID- 18709972
TI  - [Pathogenetic role of JAK2 gene mutation in chronic myeloproliferative
      disorders].

PMID- 18709973
TI  - [Evaluation of disease model mice using in vivo imaging technologies].

PMID- 18709974
TI  - [Self-renewal mechanisms of leukemic stem cells].

PMID- 18709975
TI  - [Current status of investigator-initiated clinical trials on hematological
      diseases--Northern Hematology Study Group].

PMID- 18709976
TI  - [Past and future of the Kanto Study Group for Cell Therapy].

PMID- 18709977
TI  - [Multicenter collaborative studies by Hokuriku Hematology Oncology Study Group].

PMID- 18709978
TI  - [Present status of clinical research by Nagoya BMT Group].

PMID- 18709979
TI  - [Present status and future perspective of multicenter collaborative studies by
      West-Japan Hematology Oncology Group].

PMID- 18709980
TI  - [History of clinical research and education in hematological diseases by the
      Kyushu Hematology Organization for Treatment Study Group].

PMID- 18709981
TI  - [Renaissance of basophil biology in 21st century discovery of unexpected and
      unique functions of basophil in vivo].

PMID- 18709982
TI  - [Immunosuppressive therapy with antithymocyte globulin and cyclosporine for
      paroxysmal nocturnal hemoglobinuria].
AB  - Immunosuppressive therapy (IST) for paroxysmal nocturnal hemoglobinuria (PNH) has
      been infrequently reported. Four PNH cases were treated with antithymocyte
      globulin (ATG) at our center. We assessed and reviewed the efficacy and safety of
      IST for PNH. ATG therapy was performed for progression of cytopenia in 3
      classical-type and 1 marrow failure-type PNH cases. ATG was administered at a
      dose of 15 mg/kg for 5 consecutive days. Hydration and anticoagulant therapy were
      given as prophylaxis for thrombosis during ATG therapy. Cyclosporine was also
      given to the 3 classical-type PNH patients. Three patients showed hemolytic
      exacerbation and thrombocytopenia during ATG administration, and all needed to
      receive transfusions of red blood cells and platelets; however, renal failure and
      thrombosis did not occur. Anemia improved in all cases within 1 year, but
      thereafter, recurred in 2 cases. ATG therapy is a choice of treatment for PNH,
      although its mechanism remains unknown.

PMID- 18709983
TI  - [Acute disseminated encephalomyelitis during treatment for idiopathic
      thrombocytopenic purpura].
AB  - A 54-year-old woman had an episode of sudden oral bleeding and generalized
      petechiae 1 week after a sore throat and diarrhea. On admission, the platelet
      count was 0.1 x 10(4)/microl, and the platelet-associated IgG level was elevated.
      Hyperplasia of megakaryocytes in a bone marrow specimen and aberrant Epstein-Barr
      virus (EBV) antibody patterns led to a diagnosis of EBV-associated idiopathic
      thrombocytopenic purpura (ITP). Prednisolone (PSL) promptly restored her platelet
      count; however, she developed disorientation and affective lability soon after
      PSL was tapered. Subsequently, she ran a high fever and developed convulsive
      seizures. T2-weighted MRI demonstrated a high signal area in the subcortical
      white matter, and no abnormal findings were found on examination of the
      cerebrospinal fluid. The diagnosis of acute disseminated encephalomyelitis (ADEM)
      was made and steroid pulse therapy was started, which resulted in remission of
      the symptoms without recurrence in the following months. This is the first
      reported case of ADEM following EBV infection during treatment for ITP.
      Administration of PSL for ITP might mask the presenting clinical picture of ADEM.
      The possibility of ADEM should be investigated in patients of ITP following viral
      infection who develop acute encephalopathy.

PMID- 18709984
TI  - [Chronic eosinophilic leukemia with complex karyotypic abnormalities including
      trisomy 8].
AB  - We report a 61-year-old man with chronic eosinophilic leukemia (CEL). The patient
      was referred to our hospital because of pyrexia and eosinophilia. He was
      diagnosed with CEL based on an increase in blasts and eosinophils in his
      peripheral blood and bone marrow, and clonal complex karyotypic abnormalities
      including trisomy 8. The FIP1L1-PDGFRA fusion transcript was not detected by RT
      PCR analysis. Although he had no obvious organ damage at diagnosis, pulmonary
      infiltrates in the right lung and multiple skin nodules over his whole body
      appeared over 4 months and progressed rapidly, accompanied by a marked increase
      in blasts in his peripheral blood. CEL with trisomy 8 has been reported to be
      associated with transformation into acute leukemia and granulocytic sarcoma in
      the literature. It is notable that the present case was associated with complex
      karyotypic abnormalities and the exceptionally marked disease progression.
      Further analyses of clinical data as well as molecular genetic findings of CEL
      without known karyotypic abnormalities leading to constitutive activation of
      tyrosine-kinase genes are needed to gain insight into the pathogenesis of CEL and
      to develop a new disease classification and treatment strategies.

PMID- 18709985
TI  - [Evans syndrome associated with idiopathic mixed-type autoimmune hemolytic
      anemia].
AB  - A 60-year-old man was admitted to our hospital with severe anemia and blood
      findings showed hemolytic anemia. Further serological examination revealed both
      warm-reactive autoantibody and cold agglutinin against erythrocytes. The cold
      agglutinin showed a low titer, 1 : 32 at 4 degrees C, and had a high thermal
      amplitude of 30 degrees C or higher, resulting in sufficient activity for
      hemolysis. Since no underlying disorders could be detected, the diagnosis was
      idiopathic mixed-type autoimmune hemolytic anemia. Although thrombocytopenia
      (Evans syndrome) subsequently appeared, corticosteroid was extremely effective
      for both anemia and thrombocytopenia. In this report we describe a rare case of
      Evans syndrome associated with mixed-type autoimmune hemolytic anemia, which had
      a dramatic response to corticosteroid therapy.

PMID- 18709986
TI  - New staining method for use in electrophoretic determination of alpha-amylase
      isoenzymes in serum.
AB  - We have developed and evaluated a new staining method for use in electrophoretic
      analysis of alpha-amylase (AMY, EC3. 2. 1. 1) isoenzymes in serum. Our method
      based on the colorimetric determination of formazane dye formed by enzyme-coupled
      reactions and maltopentaose was used as a substrate. We have confirmed that this
      method was sensitive and stable. Liquid reagents are used, so the automatic
      analysis of AMY isoenzymes using a fully-automated electrophoresis system will
      become possible.

PMID- 18709987
TI  - [Clinical usefulness of measurement of urine type IV collagen for detection of
      early phase of nephropathy in type 2 diabetic patients].
AB  - Urine type IV collagen concentrations in type 2 diabetic patients were measured
      by enzyme immunoassay which has crossreactivity with only intact type IV
      collagen, and the clinical usefulness for estimating the early phase of diabetic
      nephropathy was evaluated. Precision of the measurement system was satisfactory
      for clinical use and the value did not influenced by the presence of sediments in
      urine. In whole type 2 diabetic patients (N=132), urine type IV collagen
      concentration (microg/g of creatinine) increased with development of nephropathy
      and showed significantly increase even in normoalbuminuria when compared with
      that in normal control subjects (N=117). In type 2 diabetic patients (N=100) with
      mild microalbuminuria (less than 100 mg/g of creatinine), multiple regression
      analysis revealed that HbA1C was extracted as a significant valuable for urine
      type IV collagen, while body mass index was extracted as a significant valuable
      for urine albumin. In these subjects, urine type IV collagen was significantly
      lower in the patients with good metabolic control (HbA1C<8.0%) than those with
      poor control (HbA1> or =8.0%), while the urine albumin was not significantly
      different between those two groups. These results suggest that measurement of
      urine type IV collagen in type 2 diabetic patients is useful for detection of
      early phase of diabetic nephropathy.

PMID- 18709988
TI  - [Comparison of antimicrobial use density (AUD) of carbapenem antibacterial agents
      and investigation of the drug susceptibility of Pseudomonas aeruginosa in 3
      hospitals in southern Ibaraki Prefecture, Japan].
AB  - The optimal use of anti-Pseudomonas agents is an important issue in the
      prevention of a tolerance against Pseudomonas aeruginosa. We evaluated the effect
      of antimicrobial use density (AUD) of carbapenem on drug susceptibility. The AUD
      of the four carbapenems, imipenem (IPM/CS), panipenem (PAPM/BP), meropenem
      (MEPM), and biapenem (BIPM), was examined at three hospitals in Ibaraki
      Prefecture, between April and September 2004. The AUD was calculated using the
      Defined Daily Doses (DDD) methodology developed by the WHO. A drug susceptibility
      test was conducted on the 306 Pseudomonas aeruginosa strains randomly collected
      from clinical specimens at the three hospitals between September and December
      2004. In accordance with the standards set by the Clinical and Laboratory
      Standards Institute (CLSI), minimal inhibitory concentration (MIC) was measured
      using the broth microdilution method. The results showed that the AUD of
      carbapenem at the three hospitals tended to be higher than that in other research
      results in Japan. At one of the three hospitals, the AUD of the PAPM was
      remarkably high compared to the other carbapenems. Furthermore, P. aeruginosa
      strains collected at this hospital showed a low susceptibility to carbapenem, and
      many highly tolerant strains were also observed in this hospital. In order to
      maintain the susceptibility of Pseudomonas aeruginosa to carbapenem, the overall
      extent of carbapenem use must be optimal. The use of antimicrobial drugs should
      be controlled properly at each hospital, in order to prevent excessive use of
      PAPM/BP from being used over a long period of time.

PMID- 18709989
TI  - [Establishment of mail medical examination system using immediate plasma
      separating device by the self-collection blood--the method of dilution ratio
      calculation by using Internal standard for the sample with different amount of
      collecting blood].
AB  - A method of calibrating unquantified samples was developed in order to conduct
      tests from approximately 65 microl or less of self-collected whole blood from the
      finger. In this method, the dilution ratio is estimated by absorption analysis of
      an internal standard substance in the blood dilution buffer. Good results for
      replication of the dilution ratio were obtained, with a CV value of 0.99-2.78%
      and a rate of concordance with the theoretical dilution ratio of 99.4-99.8%.
      Evaluations of the utility of this system (Demecal System) were performed using
      total cholesterol measurement, and excellent correlation with the measurement
      value in plasma was achieved, with a correlation coefficient of r=0.975 at n=40
      and a regression equation of y=1.02x-2.83. Dilution of 7-fold or less is required
      to assure accuracy with this system.

PMID- 18709990
TI  - [False-positive reaction of urinary ketone bodies caused by bucillamine].
AB  - In many patients taking bucillamine, an anti-rheumatic drug, urinary examinations
      show false-positive findings for ketone on urine dipsticks, because of the SH
      radicals in bucillamine. Our group examined the frequency of false-positive
      ketone testing and the causative factors in 179 outpatients being treated by the
      Department of Rheumatology in our hospital. The samples that remained purple even
      after boiling were determined to be false-positives, because boiling volatilizes
      urinary ketones while leaving bucillamine unchanged. Forty-six of 49 patients
      taking bucillamine tested false-positive for ketone, whereas there were no false
      positive reactions among patients not receiving bucillamine. The patients showing
      false-positive reactions had significantly lower serum albumin levels, higher
      specific gravity of urine and more acidic urine. Moreover, we could predict
      whether the reaction was true-positive or bucillamine-induced false-positive by
      observing differences between the colors and levels of discoloration of the urine
      test paper. In the evaluation of ketone findings on urinary dipstick, the
      physician must ascertain whether the patient is taking bucillamine.

PMID- 18709991
TI  - [Advancement of prophylaxis and therapy for venous thromboembolism].
AB  - Recently in Japan, venous thromboembolism (VTE) [deep vein thrombosis
      (DVT)/pulmonary thromboembolism (PTE)] has increased with the Westernization of
      eating habits and aging of society. In the West, the prophylaxis guidelines have
      been discussed for many years. Unfortunately, Japan falls far behind the West in
      this area. Therefore, the necessity of thromboprophylaxis in Japanese people
      should be emphasized based on reliable VTE studies in Japan. In orthopedic
      surgery, prospective multicenter studies in Japan indicate that the incidence of
      DVT/PTE in total hip or knee replacement surgery and hip fracture surgery were
      almost equal to those in Western people. Furthermore, a multi-center, prospective
      epidemiological study in Japan revealed that the incidence of VTE following major
      abdominal surgery was 24.3%. We developed Japanese Guidelines for VTE prophylaxis
      based on the 6th ACCP guideline in 2004. The incidence of perioperative PTE in
      Japan has been investigated by the Japanese Society of Anesthesiologists since
      2002. The rate of perioperative PTE was estimated to be 4.41 per 10,000
      operations in 2002, and 4.76 in 2003; however, it decreased to 3.61 immediately
      after the guideline for thromboprophylaxis was issued and the management fee for
      PTE prophylaxis became covered by health insurance in April 2004. Furthermore, it
      markedly decreased in 2005. However, mechanical prophylaxis is not sufficient to
      prevent PTE, and advanced prophylaxis by anticoagulants, such as low-molecular
      weight heparin/selective Xa inhibitor along with unfractionated heparin
      (UFH)/vitamin K antagonists (VKA) will be essential. The advanced revised
      guidelines for VTE prophylaxis based on our clinical evidence will be established
      in the near future. As for treatment for VTE, anticoagulant and thrombolytic
      therapies are essential. In cases with VTE, UFH followed by VKA (INR: 1.5-2.5) is
      standard. In cases of PTE with shock, thrombolytic therapy such as tissue
      plasminogen activator or urokinase, catheter intervention, or surgical procedures
      under pericutaneous cardiopulmonary support should be selected based on the
      severity of PTE.

PMID- 18709992
TI  - [Desirable medical technologists in a community support hospital].
AB  - Recently, there have been marked advances in the technological strategies
      employed in medical examinations. The educational concept to nurture highly
      capable medical technologists is considered to be a priority issue by not only
      educators but also employers, even though the medical educational levels have
      markedly improved in every college and university. It is commonly acknowledged
      that the results of any examination in the clinical laboratory should be accurate
      and fed back to medical doctors as soon as possible. The business outline of
      medical technologists in our hospital is becoming more extensive because we act
      as a core hospital in the area, and so knowledge regarding many kinds of chemical
      and transfusion examinations is required in operations performed around the
      clock. Furthermore, medical doctors, clerical workers, nurses, and volunteers
      comprise a team of sophisticated workers in our hospital. To accomplish our daily
      work, character traits such as accuracy, honesty, perseverance, and ability to
      follow instruction manuals, are the most fundamental and valuable. To nurture a
      highly career-oriented medical technologist, we propose that the following should
      be focused on: self-responsibility, reduction of malpractices, economic
      profitability, brainstorming, education of subsequent generations, and the spirit
      of cooperativeness and reconciliation. Additionally, it is another basic
      requirement of competent medical technologists to learn to adapt to laboratory
      based changes in their work throughout their career. In conclusion, how to adapt
      to any social demand and learn strategies in any era should be taught in college
      or university as well as after graduation because each hospital and institute has
      a different philosophy and requirements of newcomers. It is important for medical
      technologists and doctors to develop flexible ways of thinking, although we
      sometimes might accede to traditional ways.

PMID- 18709993
TI  - [Educational program in the Medical Science Course, Kitasato University School of
      Allied Health Sciences].
AB  - The aim of education in the Medical Laboratory Science course, Kitasato
      University School of Allied Health Sciences, is to bring up train students who
      have Kitasato spirit, for careers in laboratory medicine of hospital or
      scientific staff of medical companies or as researchers. General and enlightening
      education concerning "Kitasato spirit" and professional education composed of
      major subjects was carried out in the first and during the 2nd and two third of
      3rd grade, respectively. Medical practice and research training were
      alternatively carried out for 6 months between November of the 3rd year and
      November of the 4th year, in order to gain practical experience. Two problem
      based learning (PBL) tutorial courses, "Infectious Diseases Course" and "Team
      Medical Care--Interprofessional Collaborations" were also carried out at the end
      of the 3rd and beginning of the 4th years, respectively, in order to convert a
      memory to knowledge. Team medical care course enrolls 1000 students at the School
      of Allied Health Sciences, Medicine, Nursing, Pharmacy and Kitasato College
      Applied Clinical Dietetics Course, is now one of special courses available at our
      university. This attempt is thought to result in a way of thinking that
      recognizes the importance of co-operation as a team member and personal
      contributions to actual team medical care.

PMID- 18709994
TI  - [College education of medical technologists serving in highly specialized
      hospitals].
AB  - Medical Technologists (MTs) who serve in the clinical laboratories of highly
      specialized hospitals (HSP) are required to operate highly advanced medical
      technology and to develop and evaluate highly advanced reagents or devices, and
      therefore require specialized training. Furthermore, MTs in some care units or
      diagnostic facilities of HSP are required to develop and maintain highly advanced
      medical skills. MTs who serve in HSP are called advanced specialized MTs, so
      called Clinical Laboratory Scientists (CLS), and should be distinguished from
      specialized MTs and MTs. At present, the division of MTs is not officially
      accepted; however, the number of MTs with master's degrees will increase in the
      near future, and therefore it will be necessary for the educational association
      of MTs to qualify CLS as an official title. To develop the skills necessary to
      become a CLS before graduation, students participate in a number of programs,
      i.e., freshman seminars and medical team training, advanced field courses,
      clinical training (fourth grade), and laboratory research (fourth grade). We feel
      that laboratory research is the most important tool in the education of CLS,
      because the research process is the same as repeating the cycle: plan, do,
      evaluate, and discuss. The educational staff represent another important factor
      in the education of CLS, and they have long clinical careers and strong research
      directions. Finally, the Division of Medical Technology of the School of Health
      Sciences, Department of Laboratory Medicine of Shinshu University School of
      Medicine and Shinshu University Hospital cooperate in the education of MT and
      CLS.

PMID- 18709995
TI  - [Allowable limits of analytical error which can guarantee the reliability of
      reference intervals for interpretation of clinical laboratory data].
AB  - The International Organization for Standardization (ISO) developed a guide to the
      expression of uncertainty in measurement (GUM). The purpose of such guidance is
      to provide a basis for the international comparison of measurement results. In
      this study, we propose a basic protocol to evaluate and express uncertainty in
      measurement for routine test results in the clinical laboratory. We also sought
      to investigate the effects of measurement errors on the evaluation of biological
      variations in healthy subjects. To this end, we analyzed the allowable limits of
      analytical error which guarantee the reliability of reference intervals for the
      interpretation of clinical laboratory data. As a conclusion, we suggest that 1/2
      or less of biological intraindividual variations is an appropriate criterion for
      an allowable limit of uncertainty to be applied in health check-ups, and this
      value is in agreement with previous reports. If this criterion as a marker for
      intra laboratory imprecision is met, it suggests that a given institute is able
      to evaluate time series changes in follow-up of individual data. If the reference
      interval of laboratory data for disease screening is shared by different
      institutes, it is suggested that a criterion of 1/4 or less of a biological inter
      pulse intra-individual variation is appropriate. This criterion appears to be
      the goal for analytical inter-laboratory variations.

PMID- 18709996
TI  - [Setting reference intervals without considering sex and age differences].
AB  - We compared two sets of sex and age-specific reference intervals obtained from
      two large reference populations, one set calculated with data from 700,000
      reference individuals by the nonlinear optimizing method of Ohgushi and Shibata
      and the other set calculated with data from 150,000 reference individuals from
      Shizuoka prefecture by the revised Hoffmann fitting method. Ten laboratory
      analytes used for health screening were compared. The sex- and age-specific
      reference intervals for total cholesterol, fasting blood sugar, uric acid, total
      protein, and albumin from the two large reference sample groups closely resembled
      each other, but reference intervals for the enzyme analytes aspartate
      aminotransferase, alanine aminotransferase, lactate dehydrogenase, and gamma
      glutamyl transpeptidase only partly corresponded. Surprisingly, new information
      came from comparison of the sex- and age-specific reference intervals of alkaline
      phosphatase: low activities were observed in young females and higher activities
      were observed in older females. If a reference interval is used that does not
      take this observation into account, misdiagnosis of hyperthyroidism, which is
      frequently observed in young women, may result. Sex- and age-specific reference
      intervals should be used to interpret results of laboratory screening tests.

PMID- 18709997
TI  - [The effect of operating time of PMX-DHP on decrease of platelets].
AB  - BACKGROUND: Recently, it is said that long-term PMX-DHP is beneficial for severe
      septic shock. Decrease in platelets, however, is one of the problems of PMX-DHP.
      We retrospectively examined the effect of operating time of PMX-DHP on decrease
      of platelets. METHODS: Forty-nine subjects were divided into three subgroups by
      their operating times of PMX-DHP. In short (S) group, the operating time was
      below 4 hours, and the group comsisted of 13 subjects. Intermediate (I) group
      with operating time of 4-12 hours, had 15 subjects. And long (L) group with
      operating time of 12-24 hours, had 21 subjects. Rate of decrease of platelets was
      compared between these subgroups. RESULTS: Decreased rate of platelets of each
      sub-group is as follows; S group showed 16.7 +/- 28.4%, I group showed 25.5 +/-
      28.1%, and L group showed 23.7 +/- 30.3% respectively. And there were no
      significant differences between these subgroups. CONCLUSIONS: Decreased rate of
      platelets was around 20% as previously reported and constant regardless of
      duration of operating times of PMX-DHP. Long-term PMX-DHP within 24 hours is
      practically safe in case of severe septic shock.

PMID- 18709998
TI  - [Use of landiolol hydrochloride for the prevention of atrial fibrillation after
      lung resection].
AB  - BACKGROUND: We examined the effect of landiolol hydrochloride, a selective beta1
      adrenoreceptor antagonist, on the incidence of atrial fibrillation(AF). METHODS:
      The incidence of AF after lung resection was evaluated retrospectively in
      patients with intraoperative treatment with landiolol hydrochloride or those
      without it. Landiolol hydrochloride (5 microg x kg(-1) x min(-1)) was
      administered intravenously from the beginning of anesthesia induction to the end
      of operation. RESULTS: In non-treatment group with landiolol hydrochloride (224
      patients), the incidence of AF after surgery was 14.2%, peaking on postoperative
      day 2, and the average peak day was day 3.5. Older age, removal of the lymph
      nodes, lengthy surgery, and ischemic heart failure were risk factors. In
      treatment group with landiolol hydrochloride (77 patients), the incidence of AF
      after surgery was 5.2%, which was significantly lower than that in non-treatment
      group. Increased numbers of risk factors led to the high incidence of AF. But the
      administration of landiolol hydrochloride suppressed the incidence of AF.
      CONCLUSIONS: Landiolol hydrochloride is effective for the preventionof AF and it
      is safe without causing a severe decrease in blood pressure and bradycardia in
      high risk patients.

PMID- 18709999
TI  - [Effect of heparin on the activated partial thromboplastin time in parturients
      receiving combined spinal and epidural anesthesia for caesarean section].
AB  - BACKGROUND: Although administration of heparin is a useful method for preventing
      deep venous thromboembolism, one limitation is the increased risk of bleeding. In
      this retrospective investigation, we evaluated the effect of heparin on the
      activated partial thromboplastin time (APTT) in parturients who received
      caesarean section under combined spinal and epidural anesthesia. METHODS: In
      order to prevent deep venous thromboembolism, heparin 5000 units twice daily, was
      subcutaneously given in 199 parturients who received caesarean section under
      combined spinal and epidural anesthesia. Measured APTT was compared between
      before and after administration of the heparin. RESULTS: The heparin extended
      APTT from 29.6 +/- 2.5 sec to 35.4 +/- 5.9 sec (P < 0.05). An extended APTT by
      1.5 times or more was found in 1.1% of the patients. There was no deep
      thromboembolism nor increased bleeding, including intra-abdominal and epidural
      hematoma. CONCLUSIONS: Subcutaneously administered heparin, 5000 units twice
      daily, might have a role in preventing deep venous thromboembolism in parturients
      undergoing caesarean section. Strict vigilance, however, should be provided
      against increased bleeding associated with epidural hematoma in parturients with
      an indwelling epidural catheter.

PMID- 18710000
TI  - [Effects of preoperative ketamine on postoperative pain in patients undergoing
      laparotomy].
AB  - BACKGROUND: Effects of preoperative ketamine on postoperative pain in patients
      undergoing laparotomy have been controversial. METHODS: Fifty-two patients
      undergoing elective laparotomy were enrolled in this retrospective study.
      Patients were classified into 3 groups according to anesthetic management;
      patients received general anesthesia alone with preoperative ketamine (n = 20),
      patients received epidural blockade and general anesthesia with preoperative
      ketamine (n = 15), and patients received epidural blockade and general anesthesia
      without preoperative ketamine (n = 17). Among the three groups, we compared the
      parameters concerning postoperative pain managements; frequency of complaining
      about pain, opioid consumption, incidence of nausea and vomiting in the first 24
      hours after laparotomy, and ability of ambulation on the first postoperative day.
      RESULTS: Among the three groups, there were no significant differences in all
      parameters concerning postoperative pain management described above. CONCLUSIONS:
      Results of this study imply that preoperative ketamine may elicit preemptive
      analgesic effects, and can be an efficient adjuvant to postoperative pain
      management for patients undergoing laparotomy.

PMID- 18710001
TI  - [Comparison of the effects of sevoflurane and propofol on changes in leukocyte
      count induced by surgical stress].
AB  - BACKGROUND: It is well known that surgical stress causes granulocytosis and
      lymphopenia. However, effects of general anesthetics on changes in leukocyte
      count induced by surgical stress are not still clear. METHODS: One hundred and
      sixteen patients undergoing elective surgery with general anesthesia were
      enrolled in this retrospective study. Patients were classified into two groups
      according to anesthetic agents used for maintenance of general anesthesia;
      sevoflurane group (n = 69) and propofol group (n = 47). Changes in leukocyte
      count during surgery were compared between the two groups. RESULTS: In
      sevoflurane group, lymphocyte-count increased in the early period during surgery,
      but decreased later. However, lymphocyte-count continued to increase during
      surgery in propofol group. We found a significant difference in lymphocyte-count
      during surgery between sevoflurane group and propofol group. On the contrary,
      granulocyte- and monocyte-count increased during surgery in both groups. There
      were no significant differences in granulocyte- and monocyte-count during surgery
      between the two groups. CONCLUSIONS: There were significant differences in
      effects of sevoflurane and propofol on changes in lymphocyte-count induced by
      surgical stress. Results of this study imply the efficiency of propofol to
      prevent lymphopenia, which may play an important role in postoperative
      immunosuppression caused by surgical stress.

PMID- 18710002
TI  - [Three cases of acute pulmonary thromboembolism diagnosed by transesophageal
      echocardiography].
AB  - We report 3 cases of acute pulmonary thromboembolism (PTE) diagnosed by
      transesophageal echocardiography (TEE). In all these cases, cardiovascular state
      of the patient was unstable and therefore computerized tomography and
      catheterization of the pulmonary artery for diagnosis of PTE could not be
      performed. TEE was useful for diagnosis of acute PTE. All three patients passed
      away eventually and we had a difficult experience for treatment of acute PTE. We
      should take various measures against deep vein thrombosis for prevention of acute
      PTE.

PMID- 18710003
TI  - [Prevention of postoperative nausea and vomiting by metoclopramide combined with
      dexamethasone in gynecological surgery].
AB  - BACKGROUND: The authors evaluated the efficacy of a combination of dexamethasone
      and metoclopramide for the prophylaxis of postoperative nausea and vomiting
      (PONV) after gynecological abdominal surgery. METHODS: One-hundred and seventeen
      patients scheduled for gynecological abdominal surgery were analyzed
      retrospectively. Patients were classified into three groups by anti-emetics
      administered; none (Group C, n = 38); metoclopramide 10 mg (Group M, n = 39); or
      a combination of metoclopramide 10 mg with dexamethasone 8 mg (Group MD, n = 40)
      at 30 to 60 minutes prior to the end of surgery. Anesthesia was induced by
      propofol and maintained with isoflurane-nitrous oxide inhalation and intermittent
      administration of fentanyl. Postoperative pain was treated with continuous
      subcutaneous infusion of pentazocine via a patient controlled analgesia device.
      PONV was assessed using a 5 rating verbal score in early (0-6 hr) and in late (6
      24 hr) period. RESULTS: The 3 groups were similar in demographic characteristics.
      The incidence of nausea and vomiting in early period was significantly lower in
      Group MD compared with Group C and Group M. Rescue anti-emetic requirements were
      fewer in Group MD compared with Group C. There are no severe complications.
      CONCLUSIONS: A combination of metoclopramide and dexamethasone was more effective
      in preventing PONV compared with metoclopramide alone.

PMID- 18710004
TI  - [Anesthesic management of thoracic aortic stent graft deployment using rapid
      ventricular pacing].
AB  - Controlled hypotension is useful for accurate deployment of an aortic endograft.
      We describe the use of rapid ventricular pacing during thoracic aortic stent
      graft deployment. Anesthesia was induced and maintained with intravenous propofol
      and remifentanil. A pulmonary artery catheter with pacing function was
      introduced, and rapid ventricular pacing was started before stent graft
      deployment. Pacing mode was VVI and pacing rate was 120-160 beats min(-1). Aortic
      pressure and flow decreased immediately and were maintained at low levels during
      surgical manipulation. After stopping rapid ventricular pacing, heart rate and
      aortic pressure recovered immediately. Rapid ventricular pacing was performed 4
      times, and there were no complications such as entailed arrhythmia. With rapid
      ventricular pacing maneuver, which is thought to cause a rapid change in cardiac
      output, continuous cardiac output measurement can be a useful monitor. This
      procedure has advantages over pharmacologic or other methods of aortic pressure
      reduction. Rapid ventricular pacing is safe and effective during stent graft
      positioning and deployment.

PMID- 18710005
TI  - [Anesthetic management of laparotomy for a patient with amyotrophic lateral
      sclerosis: a case report].
AB  - Amyotrophic lateral sclerosis (ALS) is a disease involving motor neurons. There
      are two major problems in anesthetic management for patients with motor neuron
      diseases; prolongation of the effect of non-depolarizing muscle relaxant, and
      controversy about a use of neuraxial block. We describe the anesthetic management
      of laparotomy for a patient with ALS by general anesthesia alone. A 55-year-old
      man, suffering from ALS, was scheduled for hemicolectomy and colostomy. General
      anesthesia was induced by intravenous administration of ketamine, thiopental and
      fentanyl. After manual ventilation using sevoflurane (5% in oxygen) for 15
      minutes, the trachea was intubated without using a non-depolarizing muscle
      relaxant. General anesthesia was maintained by sevoflurane, nitrous oxide and
      fentanyl. Since muscle relaxation required for tracheal intubation and surgical
      procedure was obtained sufficiently using sevoflurane, a non-depolarizing muscle
      relaxant was not necessary throughout the anesthetic management. The patient
      emerged from general anesthesia smoothly, and was extubated without any
      complications. For the postoperative pain management, we administered opioids
      intravenously, providing good analgesia. The postoperative course was uneventful,
      and there was no exacerbation of neurological signs and symptoms of ALS.

PMID- 18710006
TI  - [Use of the Pentax-AWS videolaryngoscope and an exchange catheter for tube
      exchange].
AB  - The Pentax-AWS videolaryngoscope (Tokyo, Japan) has been used successfully to
      intubate the trachea in patients with difficult airways. We report the use of the
      Pentax-AWS for tube exchange in a patient with difficult airway. In a 57-year-old
      man scheduled for laminectomy of the cervical spines, tracheal intubation of a
      reinforced tube was accomplished with a great difficulty. At the end of surgery,
      the patient had convulsions with irregular breathing. Emergency magnetic
      resonance imaging of the head and neck was planned, and thus it became necessary
      to exchange the metallic reinforced tube by a polyvinylchloride tube. The Pentax
      AWS (with a polyvinylchloride tube attached) was inserted, while the reinforced
      tube was still in place. Under the video image, the cuff of the reinforced tube
      was deflated, and a tube exchanger was introduced through the polyvinylchloride
      tube into the trachea, alongside the reinforced tube. The reinforced tube was
      removed, and the new tube was advanced over the exchanger into the trachea. We
      suggest that the Pentax-AWS is useful for tube exchange, as one can continuously
      confirm the entire course of exchange and can detect and rectify any possible
      problems, such as difficulty in advancing an endotracheal tube over the
      exchanger.

PMID- 18710007
TI  - [Anesthetic considerations for thymectomy in a patient having an anti
      acetylcholine receptor antibody without myasthenia gravis].
AB  - A patient having an anti-acetylcholine receptor (AChR) antibody without
      myasthenia gravis was scheduled for thymectomy. Neuromuscular blockade monitoring
      showed a normal response to vecuronium in the patient. This finding suggests that
      sensitivities to neuromuscular blocking agents in the patients depend not on the
      titers of the antibody but also on the presence or absence of the preoperative
      symptoms such as muscle weakness. It is, however, recommended that neuromuscular
      blocking agents should be administered carefully under monitoring the
      neuromuscular function, as is the case for myasthenia gravis, because little is
      understood about the effect of neuromuscular blocking agent on the neuromuscular
      function in the asymptomatic patients having anti-AChR antibody.

PMID- 18710008
TI  - [Prolonged pain after left hepatectomy].
AB  - We have experienced a patient complaining of the prolonged pain after left
      hepatectomy. The patient was a 53-year-old man. He underwent left hepatectomy for
      cholangiocellular carcinoma, and complained of prolonged abdominal pain for more
      than 10 days after the operation. After detailed examinations, we noticed
      duodenal perforation. After the conservative treatment, his pain was improved. In
      this case, the causes of the prolonged pain might be peritoneal irritation caused
      by gastric contents and duodenal perforation. The peritoneal irritation was
      caused by bile leakage and the deformity of the stomach that might be due to the
      enlarged dead space after left hepatectomy. We should be cautious of possible
      pyloric obstruction as the cause of prolonged pain after left hepatectomy.

PMID- 18710009
TI  - [Anesthetic management of awake off-pump coronary artery bypass grafting (ACAB)
      with remifentanil and thoracic epidural anesthesia].
AB  - Two patients with total occlusion of the right internal carotid artery, were
      anesthetized for ACAB with remifentanil and thoracic epidural anesthesia. Case 1:
      A 71-year-old man with hypertension and diabetes mellitus underwent single-vessel
      ACAB under IV remifentanil analgesia, the dose of which was adjusted to 0.04-0.05
      microg x kg(-1) x min(-1), along with an epidural infusion of 10 ml x hr(-1) of a
      mixture of 2% lidocaine and 2.5 microg x ml(-1) of fentanyl, the PaCO2 being
      maintained at 52-55 mmHg. When the patient felt pain, the remifentanil dose was
      elevated to 0.08 microg x kg(-1) x min(-1) and PaCO2 increased to 60 mmHg. Case
      2: A 66-year-old man with rheumatoid arthritis underwent ACAB for two grafts. An
      intraaortic balloon pump (IABP) was inserted preoperatively. The anesthetic
      method used was the same as in case 1, except for an additional right femoral
      block to provide anesthesia for extraction of the saphenous vein. Remifentanil
      was infused at 0.05 microg x kg(-1) x min(-1) and PaCO2 maintained at 49-53 mmHg.
      In response to the patient's pain and movement, the remifentanil dose was
      increased to 0.07-0.10 microg x kg(-1) x min(-1) and PaCO2 to 60 mmHg.

PMID- 18710010
TI  - [General anesthesia with remifentanil for a patient having sinoatrial block and
      constrictive pulmonary disorder].
AB  - There is little report describing the effect of remifentanil on cardiac
      conduction system. We present a successful anesthetic management with
      remifentanil in a patient with sick sinus syndrome. A 66-year-old woman (31-kg,
      121-cm) having sinoatrial (SA) block was diagnosed as having hepatic cell
      carcinoma, and radiofrequency ablation (RFA) was scheduled. She was also
      suffering from kyphosis due to the past history of tuberculous spondylitis.
      Preoperative examination of her respiratory function indicated a severe
      constrictive pulmonary disorder. Anesthesia was induced with propofol (30 mg),
      and maintained with sevoflurane (1-2%) and oxygen/air in combination with
      remifentanil (0.5 microg x kg(-1) x min(-1)). Temporary pacemaker was prepared
      during anesthesia. Neither remifentanil nor sevoflurane deteriorated SA block and
      her heart rate was well controlled. Respiratory dysfunction was not seen in the
      postoperative course. Our case suggests that remifentanil may be a suitable
      analgesic for patients with cardiac conduction abnormalities.

PMID- 18710011
TI  - [A patient undergoing surgery for gastric cancer four weeks after insertion of a
      drug-eluting coronary stent].
AB  - We report a patient who underwent gastrectomy four weeks after a coronary stent
      insertion. A 79-year-old man suffering from unstable angina was transferred to
      our hospital and a sirolimus-eluting coronary stent was inserted into his right
      coronary artery. The day after receiving the coronary stent, the patient began
      vomitting bloody gastric fluid. Endoscopic findings showed Borrmann type 3
      gastric cancer and a distal partial gastrectomy was scheduled four weeks after
      stent insertion. One week before the operation, the patient's aspirin and
      ticlopidine regimen was replaced with heparin injection, which was then
      discontinued twelve hours before the operation. After confirmation that his
      activated coagulation time was normalized, an epidural catheter was inserted and
      anesthesia was induced with midazolam 3.0 mg, fentanyl 0.1 mg and vecuronium 7.0
      mg. Then propofol administration was began with a simulated blood concentration
      of 2 microg x ml(-1). Anesthesia was maintained using propofol infusions and
      intermittent epidural injections of local anesthetics. Hypotension was treated
      using an infusion of dopamine. The surgery was successfully performed and the
      patient was intensively monitored in the ICU. Heparin was restarted three days
      after the operation, and replaced with antiplatelet therapy five days after the
      operation. Six months after his gastrectomy, the patient underwent a right colon
      resection for invasive carcinoma. No complication, such as stent thrombosis or
      bleeding, occurred during the perioperative period.

PMID- 18710012
TI  - [Intravenous leiomyomatosis with extension into the right atrium: differential
      diagnosis from right atrial myxoma by intraoperative transesophageal
      echocardiography].
AB  - Intravenous leiomyomatosis (IVL) is an uncommon neoplasm characterized by the
      growth of a benign-looking smooth muscle tumor into the venous system.
      Intracardiac extension of this tumor is rare and may be misdiagnosed as right
      atrial myxoma unless the extracardiac part of the tumor is fully evaluated. We
      report a case of a 76-year-old woman whose preoperative diagnosis was right
      atrial myxoma. Intraoperative transesophageal echocardiography (TEE) revealed
      that the tumor had an extracardiac origin, resulting in tumor removal from the
      heart chamber and a part of the inferior vena cava (IVC) under circulatory
      arrest. When the findings of no attachment of the tumor to the interatrial septum
      or the right atrial wall and the tumor extension through the IVC are obtained by
      TEE examination, IVL should be considered as a differential diagnosis.

PMID- 18710013
TI  - [Dexmedetomidine for sedation during voice monitoring surgery in a patient with
      an episode of seizure].
AB  - We present a rare case of 26-year-old male patient without a history of epilepsy,
      who underwent a voice monitoring surgery under local anesthesia plus sedation
      using modified neuroleptanalgesia. As he developed generalized tonic-clonic
      seizure probably due to pentazocine, the operation was cancelled. Later, the same
      surgery was rescheduled. After a premedication with intramuscular phenobarbital,
      the patient was sedated with dexmedetomidine and locally anesthetized, showing
      sedation of high quality with no respiratory depression and no seizure.
      Dexmedetomidine was used succesfully for voice monitoring surgery.

PMID- 18710014
TI  - [Anesthetic management of a patient with transfusion-related acute lung injury
      (TRALI)].
AB  - Transfusion-related acute lung injury (TRALI) is characterized by pulmonary edema
      and hypoxemia within 6 hours of transfusion in the absence of other causes of
      acute lung injury or circulatory overload and is now considered the leading cause
      of transfusion-related death. We report a female patient who showed hypoxemia
      after transfusion without any other causes of acute lung injury. The patient is a
      43-year-old woman, who received emergency transurethral hemostasis for bladder
      hemorrhage with hematuria and low hemoglobin concentration (3.2 g x dl(-1)).
      General anesthesia was maintained with sevoflurane, remifentanil, and vecuronium.
      Two units of RBC were transfused during operation. Since she showed high blood
      pressure, tachycardia, and a painful expression after operation, we extubated
      her. Although we gave her O2 6 l x min(-1) after extubation, she showed low
      oxygen saturation (90%), thus we started bag-mask ventilation. However, she
      complained of dyspnea and the chest X-ray revealed bilateral diffuse pulmonary
      edema following hypoxemia (80%). Thus we inserted endotracheal tube and started
      positive pressure assist ventilation. The next day, hypoxemia was improved under
      PEEP therapy. The anti-HLA antibody in the transfused plasma was positive. We
      conclude that the early recognition and management of TRALI is essential during
      and after operation.

PMID- 18710015
TI  - [Yokuininto improves treatment resistant burning pain in legs].
AB  - Yokuininto was effective in treating burning pain in both lower legs of a 58-year
      old woman. She felt her lower legs feverish: however, no neurological deficit or
      abnormal finding in angiography was found. The burning pain was increased by cold
      and decreased by warm, but was alleviated by epidural block with local
      anesthetics. After 2-week medication of Yokuininto, burning pain was reduced to
      20 to 30% and fever in legs disappeared. Yokuininto has been used for chronic
      pain in muscle and joint accompanied by swelling or local fever. This patient had
      no joint pain or swelling, but her burning pain was considered to have resulted
      from some abnormality in blood circulation due to disorder in discharge of water
      in the body.

PMID- 18710016
TI  - [A case of craniotomy with intermittent tracheal extubation for speech mapping
      during surgery].
AB  - We gave anesthesia for craniotomy in a 54-year-old man with intracranial tumor
      near the Broca speech centers causing facial nerve palsy and slight allophasis.
      Nasotracheal intubation was performed after intravenous administration of
      droperidol 15 mg and fentanyl 0.2 mg. The head was fix with 3 pins with the
      patient in the right lateral position, and endotracheal tube was withdrawn to the
      pharynx confirming the speech of the patient. The patient was intubated again
      using fiberscope after intravenous midazolam 3 mg with inhalation of nitrous
      oxide. Nitrous oxide was discontinued for 2 hours after the start of surgery for
      the speech mapping, and the patient emerged from anesthesia in 5 minutes. He
      pronounced the letters on cards during the speech mapping. After the successful
      mapping, the patient was intubated again using fiberscope after administration of
      fentanyl 0.1 mg. Anesthesia was maintained again with nitrous oxide. The patient
      recovered from anesthesia quickly after surgery without any events. On the post
      operative round, the patient could not remember well the anesthetic induction and
      the awakening during the brain mapping. Three episodes of intubation caused no
      complications, and the neurological symptoms disappeared in several days.

PMID- 18710017
TI  - [Airtraq optical laryngoscope].
AB  - BACKGROUND: We described an early experience of Airtraq laryngoscope in 20
      patients receiving general anesthesia. METHODS: In all, 2 staff
      anesthesiologists, 3 anesthesia residents and 10 non-anesthesia residents
      performed endotracheal intubation with 14 polyvinyl chloride tubes with inside
      diameter of 7-8 mm, 5 double lumen 37-F tubes and 1 preformed nasotracheal tube.
      RESULTS: Every endotracheal intubation was achieved at the first trial, and the
      mean time to secure the airway was 46 +/- 18 seconds. CONCLUSIONS: Airtraq
      laryngoscope is a useful novel device for tracheal intubation.

PMID- 18710018
TI  - [Use of gum elastic bougie for tracheal intubation: comparison of different
      tracheal tubes].
AB  - BACKGROUND: Gum elastic bougie (GEB) is one of the most useful devices for
      patients whose tracheas are difficult to intubate during anesthetic induction.
      But no previous study has evaluated the effects of the types of the tracheal
      tube. We hypothesized that wire-reinforced tracheal tubes were superior to
      standard tracheal tubes in the success rate of tracheal intubation when using
      GEB. We compared these two different types of tracheal tubes in using GEB.
      METHODS: Forty patients were subjected and randomly allocated into two groups;
      patients intubated with standard tracheal tubes (Group , n = 20) and those with
      wire-reinforced tracheal tubes (Group S, n = 20). Measured variables were
      intubation time defined as elapsed time from mouth opening to removal of GEB from
      tracheal tube, heart rate (HR), and systolic blood pressure(SBP). We also
      compared trial times of intubation and pharyngeal or laryngeal bleeding as a
      minor side effect. RESULTS: Trachea was successfully intubated in the frist
      attempt in 37 patients (92.5%), and the rest of the patients were all intubated
      at second trial. Intubation times of Group P and Group S were 41.5 +/- 13.9s and
      41.3 +/- 11.1s, respectively. There were no significant differences in HR and SBP
      between the groups. CONCLUSIONS: The type of tracheal tube would not affect the
      success rate and time of intubation when using gum elastic bougie.

PMID- 18710019
TI  - [Training of internal jugular vein cannulation: comparison of landmark method
      with ultrasound-guided method].
AB  - We compared training of internal jugular vein cannulation with ultrasound-guided
      method and that with landmark method in a group of 10 residents and that of 10
      staffs. Cannulation was increasingly successful with both methods as the training
      proceeded, and with increasingly less time and fewer number of punctures. There
      was no statistically significant difference in time or in number of punctures
      with ultrasound-guided method between the groups. Ultrasound-guided method needed
      fewer number of punctures than those with landmark method in both groups.

PMID- 18710020
TI  - [Hemostasis system and inflammation acute-phase proteins in thrombogenic
      pathologies].
AB  - New knowledge concerning the role of inflammation in activation of fibrinolysis
      and in discoordination of its components interaction has been presented in the
      review. Considerable attention was given to molecular mechanisms of the
      haemostatic protein involvement in the acute phase of inflammation. An analysis
      of their level changes according to inflammation state has been proposed for
      thrombogenic risk assessment. Abundant consumption of plasminogen in situ as a
      result of coagulation induced by moderate level of inflammation is the first
      critical point in thrombus formation. Activated protein C leakage during severe
      inflammation is another trigger of thrombogenesis leading to possible death.

PMID- 18710021
TI  - [Substrate specificity and kinetic properties of a soluble nucleoside
      triphosphatase from bovine kidneys].
AB  - Soluble nucleoside triphosphatase differing in its properties from all known
      proteins with NTPase activity was partially purified from bovine kidneys. The
      enzyme has pH optimum of 7.5, molecular mass of 60 kDa, as estimated by gel
      chromatography, and shows an absolute dependence on divalent metal ions. NTPase
      obeyed Michaelis-Menten kinetics in the range of substrate concentration tested
      from 45 to 440 microM; the apparent Km for inosine-5'-triphosphate was calculated
      to be 23.3 microM. The enzyme was found to possess a broad substrate specificity,
      being capable of hydrolyzing various nucleoside-5'-tri- as well as diphosphates.

PMID- 18710022
TI  - Expression of mouse 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 mRNA
      alternative splice variants in hypoxia.
AB  - Expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB-3)
      mRNA alternative splice variants was studied in different mouse tissues in
      hypoxic conditions in vivo. Significant increase of the expression of PFKFB-3
      mRNA was observed in the mouse lungs, testes and brain in hypoxia. Several new
      alternative splice variants of PFKFB-3 mRNA were identified in the lung, testis,
      brain and skeletal muscle. They have different length and amino acid sequence of
      C-terminal regulatory part. However, 6-phosphofructo-2-kinase and fructose-2,6
      bisphosphatase catalytic domains were identical. Moreover, the expression of
      different alternative splice variants of PFKFB-3 mRNA has shown tissue
      specificity and different levels of induction in hypoxic conditions in vivo.
      Results of this investigation indicate a possible role of PFKFB-3 splice isoform
      in cell adaptation to hypoxic conditions.

PMID- 18710023
TI  - [Peculiarities of leukotrienes metabolism in vitamin E deficiency in rats].
AB  - Some changes take place in the spectrum of fatty acid, cholesterol and individual
      phospholipids' composition in the rat liver, under E-hypovitaminosis, that can
      play a considerable role in the cell damage. The level of cysteinyl leucotriene
      decreases in the blood and liver under E-hypovitaminosis and it rises to the
      control level under vitamin E correction. This demonstrates the influence of
      tocopherol on 5-LO pathway arachidonic acid.

PMID- 18710024
TI  - [Effect of pentosan polysulphate (SP-54) on the level of prion physiological form
      in rat tissues].
AB  - It is established that except for already known influence of pentosan
      polysulphate (SP-54) on the expression of pathological prion, this preparation
      has an inhibiting effect in respect of physiological prion. Moreover, the
      reduction of concentration of physiologycal prion is registered in the central
      and peripheral organs of the prion-replicating system. It was also shown that
      inhibition of the studied protein leads to the growth in copper and zinc
      concentration in the proper organs and tissues, but at the same time activity of
      Cu/Zn-dependent superoxide dismutase does not change.

PMID- 18710025
TI  - [Histone specific proteinase and DNase activity of spleen lymphocyte nuclei
      during oncogenesis and under the effect of hydrobromide-5-(5',6' benzocoumaroyl
      3')-methylaminouracil].
AB  - The features of histone proteolysis, their carbonylation level and
      endonucleolysis intensity were studied in the spleen lymphocytes of rats with
      transplanted Guerin's carcinoma and under the conditions of hydrobromide-5-(5',6'
      benzocoumaroyl-3')-methylaminouracil (BCU) action. The intensification of
      oxidizing histone destruction and histone-specific protease activity during
      oncogenesis and under conditions of BCU action was shown. DNase I and DNase II
      enzymatic activities of spleen lymphocytes of rats with tumour were decreased on
      different stages of tumour development, however, they were increased under
      conditions of chemical compound administration.

PMID- 18710026
TI  - [Role of non-haem iron in protecting effect of ecdysterone on development of
      streptozocin-induced hyperglycaemia in rats].
AB  - Chronic hyperglycaemia (60 days) which developed after streptozotocine (STZ)
      administration (5 mg/100 g) in rats was accompanied with development of severe
      endothelial dysfunction as well as with disturbed non-haem iron metabolism. It
      was established by EPR spectroscopy method that STZ administration reduced
      transferrin levels in the blood as well as pools of iron associated with blood
      transferrin and with ferritin in the heart and aorta of rats with hyperglycaemia.
      Chronic ecdysterone administration (100 ng/100 g, 60 days) protects
      hyperglycaemia development by preventing of non-haem iron metabolism disturbance.
      These data suppose participation of non-haem iron in mechanisms of ecdysterone
      protection of streptozotocine-induced hyperglycaemia and ischemia.

PMID- 18710027
TI  - [State of antioxidant defense and L-arginin-nitrogen oxide system in blood of
      patients with urogenital chlamydiosis].
AB  - The system L-arginine-nitrogen oxide plays a significant role in maintenance of
      the anti-infectious protection of an organism. A condition of the given system
      and activity of a enzymatic part of antiradical protection in the blood of
      patients with chlamydiosis has been studied. Obtained data specify an
      intensification of processes of an oxidizing way of recycling of arginine in an
      organism of patients. Substantial increase of NO-synthase activity and
      insignificant activity of arginase in the blood is revealed. The level of nitrite
      anion in blood cells of patients authentically increases: 1.7 times in
      erythrocytes, and 1.4 times in lymphocytes. It is shown, that in patients with
      chlamydiosis glutathione system is intensified, that is evidenced by an increase
      glutathione-peroxidase activity and authentic increase of glutathione level. It
      is assummed that the established features of nitrogen oxide exchange play a
      significant role in formation of a pathological condition at urogenital chlamydia
      infections.

PMID- 18710028
TI  - [Immunosuppressive characteristics of N-stearoylethanolamine a stable compound
      with cannabimimetic activity].
AB  - Results of investigation of biochemical mechanisms of N-stearoylethanolamine
      (NSE) influence on the processes of allergic responses of immediate and delayed
      type (anaphylactic shock in guinea pigs and contact hypersensitivity to 2,4
      dinitrochlorobenzene in mice) are presented in the paper. NSE was given per os
      during two weeks. It was found that in anaphylactic animals, NSE prevented the
      growth of histamine levels in the heart, kidneys and spleen, suppressed NO2(-)
      level increase in these organs and promoted its normalization. At the same time
      NSE prevented the decrease of the level of stable metabolite of nitrogen oxide -
      nitrite-anion (NO2(-)) in the liver and to a lesser degree in the lungs, and also
      decreased the activity both inducible and constitutive NO-synthases. NSE
      normalized the content of TBA-reactive products in the lungs and decreased it in
      the heart, diminished the decline of activity of glutathione peroxidase, catalase
      and superoxide dismutase. Effects of NSE depended on its daily dose. About 70% of
      animals which received NSE in a dose 65 mg/kg of body weight had no fatal outcome
      after the induction of anaphylactic shock. NSE suppressed the delayed type
      hypersensitivity response and normalized NO2(-) content in the blood plasma of
      mice but only at the dose of 50 mg/kg of weight. In the thymus of sensitized mice
      NSE diminished the content of NO2(-). Thus, though NSE has no affinity for
      specific CB receptors, in other words, it is not a typical endocannabinoid, its
      ability to influence the immediate and delayed type allergic reactions opens a
      perspective for creation of new medications which differ principally from
      existing pharmacological drugs with anti-allergic and immunosuppressive
      properties.

PMID- 18710029
TI  - [Lipogenesis and cholesterogenesis in the liver of rats after cholesterol
      loading].
AB  - Intensity of fatty acids and separate classes of lipids synthesis was studied in
      vitro in the liver of white rats at loading by cholesterol in the dose of 300
      mg/kg once a day during 30 days by incubation of organ homogenate with [6-(14)C]
      glucose, [2-(14)C] lysine, [1-(14)C] palmitic acid with following determination
      of radioactivity of fatty acids, phospholipids, cholesterol, acylglycerols
      radioactivity was investigated. The inhibition of fatty acids and separate
      classes of lipids synthesis in vitro in the liver of white rats at loading by
      cholesterol at the use of [6-(14)C] of glucose and [2-(14)C] lysine, as
      predecessors of fatty acids and lipids and stimulation of lipids synthesis at the
      use of [1-(14)C] palmitic acid as the predecessor was established. The loading of
      white rats by cholesterol results in its synthesis inhibition in the liver during
      incubation of its homogenates with [6-(14)C] glucose and does not influence the
      cholesterol synthesis during incubation of homogenates with [2-(14)C] lysine and
      [1-(14)C] palmitic acid. Thus synthesis of fatty acids and their use in the
      phospholipids and acylglycerols synthesis in the liver of white rats with
      hypercholesterolemia sharply decreases during incubation of their homogenates
      with [6-(14)C] glucose and [2-(14)C] lysine, and the synthesis of cholesterol,
      phospholipids and acylglycerols - increases during incubation with [1-(14)C]
      palmitic acid.

PMID- 18710030
TI  - [Effect of diet overloaded by fats on the enzyme systems of metabolism in rats].
AB  - The feeding of rats with high-fat diet (a part of fats was 50% of energy value of
      ration against 20% in control) during 4 weeks increased the level of cytochrome P
      450 in the liver and enhanced aniline- and p-nitrophenol hydroxylase activity of
      CYP2E1 as well as erythromycin N-demethylase activity of CYP3A; the activity of
      aldehyde dehydrogenase class 3, UDP-glucuronosyl transferase, glutathione-S
      transferase and N-acetyl transferase. At the same time, the moderate decrease of
      indomethacin-O-demethylase of CYP2C both phenolsulfotransferase activity were
      fixed. The changes of enzymatic activity correlated with activating of processes
      of gluconeogenesis, glycogenolysis and, especially, ketogenesis. A high-fat diet
      enhanced reactions of biotransformation of amidopyrine, acetanilide, toluene,
      sulfadimezine, were catalyzed with CYP2E1, CYP3A and enzymes of conjugation,
      simultaneously it increased the hepatotoxicity of paracetamol.

PMID- 18710031
TI  - [Effect of heavy metals on activity of key enzymes of glyoxylate cycle and
      content of thiobarbituric acid reactive substances in the germinating soybean
      Glicine max L.seeds].
AB  - The influence of CoCl2 and CdCl2 on the activity of isocytrate lyase, malate
      synthase and NAD-malate dehydrogenase in the seed lobes and the composition of
      malondialdehyde products at early stages of germinating of soybean seeds: after
      first 24-hours, 72 hours and 96 hours are investigated. It is shown that when
      germinating in the medium containing no metal salts, isocytrate lyase activity is
      greatly increased during 96 h and malate synthase is increased after 72 h and is
      decreased after 96 h of germination period. CoCl2 activated isocytrate lyase
      activity after 72 hours and decreased malate synthase activity after 96 hours.
      The lengthening of the primary root under such conditions is noted. CdCl2
      inhibited isocytrate lyase activity during first 24 hours and suppressed malate
      synthase activity after 96 hours. During this process the germ growth is
      suppressed. CoCl2 increased the composition of malondialdehyde products during
      each period of germination, and CdCl2 increased malondialdehyde content after 72
      and 96 hours. The role of glyoxylate cycle enzymes in transforming fatty acids
      into carbohydrates and in forming the primary root under the process of
      germination of seed lobes of soybean is discussed.

PMID- 18710032
TI  - [Elastolytic activity of bronchoalveolar lavage fluid in acute lung inflammatory
      injury].
AB  - Elastolytic activity in bronchoalveolar lavage fluid in the lung with acute
      inflammatory injury and properties of different proteinase inhibitors for its
      correction was established. It was determined, that 4/5 of elastolytic activities
      are submitted to neutrophile serine proteinase (EC 3.4.21.37) and 1/5 of
      elastolytic activities - metalloenzymes macrophages origin (EC 3.4.24.65).
      Inhibition of elastase-like activity with the use of three proteinase inhibitors:
      contrycal, ingiprol and thermo- and acid-stable proteinase inhibitor from rabbit
      blood showed more intensive ability of thermo- and acid-stable proteinase
      inhibitor to inhibit pancreatic elastase and pull of neutrophil and macrophage
      elastase. Preventive use and treatment of proteinase inhibitors effectively
      suppressed activation of proteinases in the acute lung inflammatory injury.

PMID- 18710033
TI  - [Effect of metal microelements on biochemical indices of probiotic bacteria].
AB  - The influence of metal-microelements (Zn, Cu, Ag, Au) in colloid and ionic form
      on the main biochemical parameters (ATP-ase activity, transmembrane potential and
      respiratory activity) of E. coli G35 N#1-413 and Ent. faecalis G35 N#4-410
      probiont-strains has been studied with the goal to create complex metal-bearing
      probiotic preparations. Monotonous dose-dependent inhibitory influence of all
      mentioned metals in ionic form on the bacteria functional activity has been
      established. Metals' colloids had certainly stimulating influence on
      microorganisms' biochemical parameters in the same concentration limits with the
      following maximum positive effects: for Zn - 2x10(-7)-2x10(-4) mg/ml, for Cu -
      8.4x10(-7)-8.4x10(-6) microg/ml, for Ag - 23x10(-7)-23x10(-4) microg/ml, for Au -
      5x10(-6) microg/ml by metals. It has been shown, that cultural characteristics of
      probiont-bacteria in the presence of both ionic and colloid forms of studied
      metals remain stable. Certain stimulation of probiont-bacteria' main enzymes and
      life-support processes by colloidal forms of the studied metals-microelements in
      determined concentration and particle dimension limits is the evidence of a
      possibility of metals' colloids application in probiotic preparations'
      composition in order to increase the resistance and functional activity of
      probiont-microorganisms.

PMID- 18710034
TI  - [Cyanidin as endogenous chelator of metal ions in maize seedling roots].
AB  - The property of cyanidin complexation with different metal ions in maize
      seedlings roots was established using parameters of reflectance spectroscopy and
      colorimetry. The spectral criteria of pigment association with metals in vivo
      were evaluated.

PMID- 18710035
TI  - [Effect of presowing treatment of spring wheat seeds with wheat germ agglutinin
      on the chlorophyll content, lectin activity in leaves and nitrogen-fixing
      capacity of rhizospheric microorganisms].
AB  - The response of spring wheat and rhizospheric nitrogen-fixing micro-organisms to
      the presowing treatment of seeds by wheat germ agglutinin was investigated in
      conditions of green house experiments. It was shown, that exogenous lectin
      induced the metabolic changes in plants and caused an increase in chlorophyll
      content and activity of endogenous lectins in the leaves, as well as enhanced
      accumulation of plants biomass and nitrogen-fixing capacity of the rhizospheric
      micro-organisms. These results evidence for the considerable role of exogenous
      lectin as a regulator of growth and development of plants and activity of the
      nitrogen-fixing microorganisms.

PMID- 18710036
TI  - [Influence of direct electric current on hydrodynamic diameter of human serum
      albumin].
AB  - The effect of the weak electric current (2 mA/cm2) on structural characteristics
      (hydrodynamic diameter and molecular weight) of the human serum albumin (HSA) was
      studied using photon correlation spectroscopy (PCS). The average diameter of
      initial HSA globule is approximately 7 nm (66.8 kDa). After electric current
      treatment during 2-5 min the diameter of HSA monomer increases to 7.5 nm. The
      duration of electric current treatment being increased to 20 min the size of HSA
      monomers decreases to 6.4 nm. The behaviour of HSA oligomers is close to that of
      monomers. Consequently, changes in the sizes of monomers and oligomers of HSA
      under the electric current treatment are caused by the change in the charge
      density stimulating change of tertiary structure of molecules and possible
      addition of ions from the buffer solution to them.

PMID- 18710037
TI  - [Age-related peculiarities of glutathione content changes in the brain of rats
      during immobilization stress].
AB  - The work is aimed at studying age-related peculiarities as regards glutathione
      content changes in the brain of rats under immobilization stress. It has been
      established that some changes in the content of reduced glutathione take place in
      the brain in the process of ontogenesis. During immobilization stress the content
      of this metabolite decreases in the brain of all age groups of rats under study.
      To a greater extent this shift manifests itself in 2- and 24-month-old rats which
      are characterized by more active stress-stimulated free-radical processes in the
      brain and by an initially higher level of reduced glutathione.

PMID- 18710038
TI  - [Mathematical modeling of transmembrane calcium transport kinetics in smooth
      muscle cells].
AB  - A mathematical model, which describes kinetics of transmembrane calcium transport
      in a smooth muscular cell, has been elaborated and investigated taking into
      account that the change of calcium cations concentration within a cell is
      determined by two mutually opposite processes: an increase of a carrying capacity
      of calcium channels of plasma membrane under signal substance action and calcium
      removal from the intracellular space by Mg2+, ATP-dependent calcium pump
      localized on the plasma membrane. The fundamental difference of the proposed
      model against the models analyzed in literature before is that the cellular
      system returns to the initial stationary state after enzyme-catalysed
      transformation of the signal substance. The results of calculations showed that
      this model really described the experimental kinetics of the transmembrane
      calcium transport. In this paper the influence of different parameters (Michaelis
      constant and ultimate rate of calcium pump, initial concentrations of signal
      substance and enzyme decomposing it, rate constants) on kinetics of calcium
      transport through the plasma membrane has been investigated in detail.

PMID- 18710039
TI  - [Efficiency of partial pneumonectomies in patients with multidrug-resistant
      tuberculosis].
AB  - The immediate results of partial resections were analyzed in 120 patients with
      drug-resistant pulmonary tuberculosis, among whom 70 patients had multidrug
      resistance. A complete clinical effect (abacillation and no decay cavities) was
      achieved in 117 (97.5%) patients, including in 67 (95.7%) patients with multidrug
      resistance who showed improvement in 3 (2.5%) cases, fatal outcomes being absent.

PMID- 18710040
TI  - [Spontaneous pneumothorax in patients with tuberculosis and nonspecific diseases
      of the lung].
AB  - The clinical manifestations of spontaneous pneumothorax were determined in
      patients with respiratory tuberculosis and nonspecific lung diseases. Spontaneous
      pneumothorax was shown to be a group of complications of lung disease, which is
      heterogenic in the clinical course and outcomes. Moreover, its morphological
      basis was pulmonary emphysema, a destructive specific process, or a concomitance
      of these diseases. In patients with spontaneous pneumothorax, its severity was
      determined by the continuosly functioning bronchopleural fistula.

PMID- 18710041
TI  - [Tuberculin diagnosis in children with a family history of allergy].
AB  - Two hundred and eighteen Mycobacterium tuberculosis-infected children and
      adolescents aged 4 to 18 years were examined. Whether the patients and their
      relatives had a history of allergic reactions was ascertained. A complex of
      diagnostic studies is of great value in verifying the presence of concomitant
      allergic diseases. The rate of allergic reactions in the child's history does not
      itself determine the likelihood of development of allergic states. The Mantoux
      (tuberculin) test in allergic children does not lead to an exacerbation of the
      underlying disease at remission. The remission manifestations of paraallergy are
      noted in 15.8% of the patients with allergic diseases and in 42.9% of the
      children having allergic reactions in the history. This supports the quality of a
      follow-up and treatment by an allergist, as well as an adequate response to a
      Mantoux test with 2 TE of PPD-L in the bulk of allergic children. The use of
      antihistamines as preparation for the test allows an inference about true
      infection and the sensitivity to tuberculin in both the most of allergic patients
      and persons with a history of allergic manifestations.

PMID- 18710042
TI  - [Cardinal problems of the regional bacteriological laboratories of tuberculosis
      facilities].
AB  - Restructuring the health care system and the epidemiological situation associated
      with tuberculosis result in an increased burden on the bacteriological
      laboratories (BLs) of tuberculosis facilities. At present, there are no
      statistical data that enable one to estimate the capacity of a laboratory service
      to assure the adequate quality and efficiency of bacteriological diagnosis. To
      assess the state of the headquarters BLs of tuberculosis facilities, the authors
      have worked out a questionnaire to glean necessary information on the activity of
      the laboratories to such an extent that suffices to reveal cardinal problems in
      the work of individual laboratories and the laboratory network as a whole. Out of
      the 48 questionnaires sent from the regional BLs, the data available from 22
      laboratories that had fully answered all the questions were analyzed. The data
      obtained are referred to as of 2004, i.e. when the current antituberculous care
      projects were launched, which is of significance in organizing the monitoring of
      a laboratory service and in assessing the progress of the projects. The authors
      have identified the following cardinal problems: inadequate readiness of most
      laboratories to fully perform their incumbent functions; no coordination in
      providing data at the regional and federal levels; inefficient laboratory
      diagnosis that is associated with the disintegration of the curatorial
      institution, with neither reference relations no united external or internal
      quality control programs, with the lack of expertise and the undermanning of the
      laboratories, with the obsolete list of staff members and the obsolete standards
      for calculation of their loads, with the deterioration of a material and
      technical base, and with the unconformity of equipment to the state-of-the-art
      technologies. In order to solve the above problems, the authors offer a
      laboratory service monitoring system based on the proposed questionnaire,
      followed by the computerization of data collection and the compulsory supervision
      of regional laboratories by the officials of district and federal BLs.

PMID- 18710043
TI  - [Experience with complex radiation monitoring and treatment in a female patient
      with renal cavernous tuberculosis].

PMID- 18710044
TI  - [Organization of antituberculous care at the municipal level. Sections 9, 10,
      11].

PMID- 18710045
TI  - [The diagnosis and course of progressive disseminated pulmonary tuberculosis].
AB  - A hundred and forty-six patients with disseminated pulmonary tuberculosis were
      examined. Hematogenous disseminated tuberculosis at this stage was ascertained to
      run more frequently as acute and acutely progressive. The proportion of
      lymphogenous tuberculosis was shown to increase among all the types of
      disseminated pulmonary tuberculosis. Identification of the lymphobronchogenic
      type of disseminated pulmonary tuberculosis is recommended.

PMID- 18710046
TI  - [New-onset pulmonary tuberculosis patients with schizophrenia: course and
      efficiency of treatment].
AB  - To investigate the specific features of the course and efficiency of treatment,
      the authors examined 72 patients with new-onset pulmonary tuberculosis and
      schizophrenia versus 68 new-onset pulmonary tuberculosis patients without mental
      diseases. Tuberculosis has been found to be identified in 66.7% of schizophrenics
      by lung fluorography made at a mental hospital or specialized dispensary. This
      mainly diagnoses the circumscribed forms of the disease with a low bacterial
      discharge, drug resistance, and cavitation while in nonschizophrenics, pulmonary
      tuberculosis is detected in 33.3% of cases in general health care network
      facilities. Following 9 months, complex treatment of pulmonary tuberculosis in
      schizophrenics succeeded in ceasing bacterial discharge, as shown by microscopy
      and sputum cultures, in 94.4 and 84.5% of cases, respectively. However, in
      schizophrenics receiving chemotherapy for tuberculosis, adverse reactions are
      revealed in 63.9% of cases, with this the incidence of these reactions depends
      not only on antituberculosis drugs, but also on drugs taken by patients for
      schizophrenia. Schizophrenic patients with pulmonary tuberculosis need an
      individual approach to treating the patient, longer treatment, intermittent use
      of antituberculosis agents, regular clinical and laboratory monitoring of the
      development of side effects, and complex pathogenetic treatment.

PMID- 18710047
TI  - [Detection of pulmonary tuberculosis in patients with mental disorders].
AB  - X-ray study is the main way of detecting tuberculosis in patients with mental
      disorsers. As dysadaptation progresses in the mentally ill, the detection rate of
      lung tissue destruction increases with the simultaneous reduction in the number
      of those discharging bacteria and the role of medical attendants increases in the
      goal-oriented selection of patients for an in-depth examination for a tuberculous
      process.

PMID- 18710048
TI  - [Real-time polymerase chain reaction in the diagnosis of pulmonary tuberculosis].
AB  - To enhance the efficiency of diagnosis of oligo- and abacillar pulmonary
      tuberculosis and its differential diagnosis with other lung diseases, the authors
      studied the informative value of real-time polymerase chain reaction (PCR) used
      in 62 patients with different clinical forms of tuberculosis and 108
      differentially diagnostic patients. Real-time PCR has been ascertained to be a
      significantly more sensitive and highly specific tool in tuberculosis diagnosis,
      which considerably improves the specific recognition of the etiology of a
      pathogenetic process in oligo- and abacillar patients. Particularly encouraging
      results have been obtained when examining differentially diagnostic patients with
      the rounded shadows being formed in the lung.

PMID- 18710049
TI  - [Laser therapy in complex treatment for early tuberculosis of peripheral lymph
      nodes].
AB  - The high efficiency of etiopathogenetic treatment was established in patients
      with the proliferative form of isolated tuberculosis of peripheral lymph nodes,
      by using a combination of antituberculosis chemotherapy and low-energy laser
      radiation without surgical intervention. At the same time after 2.5-3-months,
      there was a persistent improvement, suggested by the elimination of clinical and
      laboratory signs of tuberculosis intoxication, disappearance of enlarged lymph
      nodes and a tendency of the body's tuberculosis sensitivity to reduce, evidenced
      by Mantoux 2 TE PPD-L test. The paper shows it efficient to pursue medical
      treatment policy in early isolated tuberculosis of peripheral lymph nodes.

PMID- 18710050
TI  - [Evaluation of nonspecific responsiveness from adaptive reactions in patients
      with destructive pulmonary tuberculosis].
AB  - The frequency and nature of adaptive reactions were studied by the procedure
      described by L. Kh. Garkavi in 308 patients with destructive pulmonary
      tuberculosis in relation to the carriage of different combinations of genetic
      markers. Reactions of the stress type were most frequently established in
      patients with caseous pneumonia and fibrocavernous tuberculosis (60.9+/-10.1 and
      56.4+/-7.9%, respectively). Stress was significantly often seen in patients who
      carried unfavorable and relatively unfavorable combinations of genetic markers
      (66.6+/-8.2 and 42.8+/-3.7%, respectively) and their change during treatment was
      insignificant. At the same time, patients with a carriage of favorable and
      relatively favorable combinations of genetic markers showed adequate reactions of
      training and activation. The nature of adaptive reactions correlated with the
      pattern of pulmonary tuberculosis and the level of biochemical inflammatory
      markers.

PMID- 18710051
TI  - [The course of generalized tuberculosis in a northern region].
AB  - The course of generalized tuberculosis in a northern region is mainly
      characterized by its subacute onset; moreover, the symptoms of intoxication and
      the bronchopulmonary manifestations of the disease are observed practically in
      all patients. Socially dysadapted individuals are most susceptible to this
      disease. Even if patients with generalized tuberculosis have significant symptoms
      of the diseases, only a few of them resort to a health care facility within a
      month after their occurrence. Hematological changes suggest the implication of
      suppressed immunity in the development of this form of tuberculosis and support
      the intensiveness of the disease. Bacterial discharge is noted in all virtually
      patients (80%). However, the Mantoux test is frequently of no informative value
      in diagnosing generalized tuberculosis. X-ray is always widely used; decay
      cavities are encountered in most patients. In addition to lung lesions,
      generalization of a tuberculous process is attended by the appearance of specific
      changes in the liver, spleen, kidneys, serous membranes, and peripheral lymph
      nodes.

PMID- 18710052
TI  - [Female tuberculosis morbidity and mortality in the Sverdlovsk Region].
AB  - In 2000 to 2006, the female proportion increased in the structure of tuberculosis
      morbidity from 21.4 to 30.1% and in that tuberculosis mortality from 13.1 to
      21.4% in the Sverdlovsk Region. Female tuberculosis morbidity increased mainly at
      the age of 25-34 years (by 50.9%) and 35-44 years (by 66.0%) and tuberculosis
      mortality by 2.7 times and 42.1%, respectively. The increase was due to the
      proportion of socially poor unemployed women. Pregnancy and lactation worsened
      the course of tuberculosis resulting in death in 1.3% of young women. Of the
      greatest importance was a patient's poor social status: only 6% of the women with
      tuberculosis leading to death were employed; 2.8% were dying. A portion of those
      who died from tuberculosis were drug addicts (5.4%) and HIV infected (12.3%).

PMID- 18710053
TI  - [Tuberculin diagnosis in children. Latent tuberculosis?].
AB  - The 2000-2006 results of tuberculin diagnosis made in a city numbering 10.5
      million people were retrospectively analyzed on the basis of an epidemiological
      tuberculosis survey among children. The higher cut-offs are not helpful in
      interpreting the tuberculin test. With more than 5 mm, it is necessary to have
      criteria for clear differences between the active tuberculous process, inactive
      tuberculous changes, and recent or previous Mycobacterium tuberculosis infection.
      With the low prevalence of tuberculosis among children in a megapolis, the
      sensitivity of the method was 97.4%. Its specificity was 41.7%; out of these
      children, a risk group forms in 1% of cases and the children who had been
      referred by a pediatrician and had failed to be examined by a specialist at a
      tuberculosis dispensary. With positive and negative tests, the likelihood of the
      disease in a child is 0.01 and 99.9%, respectively. At the same time, morbidity
      in risk group children formed by the results of tuberculin tests is high and
      indicative of a need for searching for objective indicators (except for
      tuberculin diagnosis and history data) to identify the disease just before
      registration as a risk group. The practical value of chemotherapy for latent
      tuberculosis infection in the megapolis requires studies and evidence-based
      results. Preventive chemotherapy is currently the priority in preventing
      tuberculosis for individual risk groups (among the HIV-infected and those who are
      from tuberculosis infection foci).

PMID- 18710054
TI  - [A case of unclassified bronchial malformation].

PMID- 18710055
TI  - [The working meeting of the leading phthisiologists of Russia on "Role and place
      of fluoroquinolones in the treatment of patients with tuberculosis"].

PMID- 18710056
TI  - [From the early history of the Moscow Mariinsk Hospital for the poor (on the
      200th anniversary of its foundation)].

PMID- 18710057
TI  - [Intensive chemotherapy of new-onset pulmonary tuberculosis in patients with
      diabetes mellitus and in elderly and senile patients].

PMID- 18710058
TI  - [Organization of antituberculous care at the municipal level. Sections 13, 14].

PMID- 18710059
TI  - [The role of interleukin-6 in rheumatoid arthritis].
AB  - Cytokines such as TNF-alpha and IL-1beta play key roles in driving the
      inflammation and synovial cell proliferation that characterize rheumatoid
      arthritis (RA) joint destruction. It is, therefore, not surprising that therapies
      for RA have targeted these cytokines. While blockade of TNF-alpha or IL-1beta has
      been efficacious for many patients with RA, adequacy and maintenance of response
      are not universal, and increased risk of adverse events such as infections and
      malignancy remain a concern. Therefore, new targets in the treatment of RA
      continue to be examined. As interleukin-6 (IL-6) has been implicated in the
      pathogenesis of RA, blockade of its activity is of both scientific and clinical
      interest. Tocilizumab has been assessed in a number of studies in recent years,
      mainly in patients with rheumatoid arthritis. Data from randomized controlled
      clinical trials demonstrate the effectiveness of tocilizumab in improving the
      signs and symptoms of RA. In addition, it appears that such inhibition of IL-6
      can have positive effects on functional status, an important outcome for RA
      patients. Finally, data suggest that treatment with this agent may also inhibit
      the progression of disease as assessed radiographically. Data from recent studies
      will help to refine the ultimate use of this novel approach to treatment, and
      help clinicians to optimize therapy using this approach.

PMID- 18710060
TI  - [Percutaneous electrical nerve stimulation of peripheral nerve for the
      intractable occipital neuralgia].
AB  - Occipital neuralgia is characterized by pain paroxysm occurring within
      distribution of the greater or lesser occipital nerves. The pain may radiates
      from the rear head toward the ipso-lateral frontal or retro-orbital regions of
      head. Though known causes include head injuries, direct occipital nerve trauma,
      neuroma formation or upper cervical root compression, most people have no
      demonstrable lesion. METHOD AND MATERIALS: A sample of 8 patients (5 females, 3
      males) aging 63,5 years on the average with occipital neuralgia has been
      recruited. The occipital neuralgic pain had presented since 4, 6 years and they
      had been treated by pharmacological therapy without benefit. Some result has been
      obtained by blocking of the grand occipital nerve so that the patients seemed to
      be suitable for subcutaneous peripheral neurostimulation. The pain was evaluated
      by VAS and SVR scales before treatment (TO) and after three and twelve months
      (T1, T2). RESULTS: During the follow up period 7 patients have been monitored for
      a whole year while one patient was followed only for 3 months in that some
      complications have presented. In the other 7 patients pain paroxysms have
      interrupted and trigger point disappeared with a VAS and SVR reduction of about
      71% and 60%, respectively. CONCLUSIONS: Our experience demonstrates a sound
      efficacy of such a technique for patients having occipital neuralgia resistant to
      pharmacological therapies even if action mechanisms have not yet clearly
      explained. Some hypothesis exist and we think it might negatively affect the
      neurogenic inflammation that surely acts in pain maintaining.

PMID- 18710061
TI  - [Nutritional dynamic monitoring during pregnancy: a personalized intervention of
      prevention].
AB  - Obesity is an increasing condition spreading out in all of the world,
      independently by race, sex and age. Obesity in pregnancy represent a risk
      condition for both mother and her offspring. All of the studies are observational
      and show intervention strategies on weight gain improvement during gestational
      period, a current topic, but still controversial. Our study is based on
      nutritional dynamic monitoring during pregnancy in order to improve health and
      wellbeing status of both mother and her offspring, through an early and efficacy
      prevention.

PMID- 18710063
TI  - [Role of cortisol hypersecretion in the pathogenesis of osteoporosis].
AB  - The negative effect on bone due to the glucocorticoid excess is mediated by the
      direct action of cortisol in reducing bone apposition and increasing bone
      resorption, and by indirect mechanisms such as the calcium malabsorption,
      hypercalciuria and hypogonadism. The condition of overt hypercortisolism, also
      called Cushing's syndrome, leads to osteoporosis and fractures in up to the 70%
      of cases, even in the presence of normal gonadal status and in males. The
      recovery from Cushing's syndrome leads to a normalization of bone mineral density
      only after several years, even if some data show that the risk of fractures
      normalizes after one year from the cure. Alendronate has been demonstrated to be
      useful to accelerate the restoration of normal bone mass after the cure of
      Cushing's syndrome Several studies, even not all, have been demonstrated that
      also the condition of asymptomatic or "subclinical" hypercortisolism (often
      associated to adrenal adenoma) is associated to a reduction of bone mineral
      density and increased prevalence of fracture even in the presence of eugonadal
      status and in males. Unfortunately, data regarding the effect of the
      normalization of cortisol secretion on bone mass and risk of fractures are
      lacking. On the other hand, it is known that osteoporotic fractures may be the
      clinical presentation of an otherwise asymptomatic hypercortisolism. In a recent
      study we have demonstrated that in a population of outpatients with established
      osteoporosis and without known or clinically evident secondary causes, the
      prevalence of subclinical hypercortisolism is about 10%. This finding suggests
      that the presence of subclinical hypercortisolism has to be taken in to account
      when evaluating patients with unexplainable established osteoporosis.

PMID- 18710062
TI  - [Mycoplasma pneumoniae encephalitis in immunocompetent child].
AB  - Mycoplasma pneumoniae is a common cause of community-acquired pneumonia, but this
      organism can also affect almost every organ system besides the lung. Neurological
      manifestations (meningitis, encephalitis, transverse myelitis, Guillain-Barre
      syndrome) are the most frequent extrapulmonary complications of Mycoplasma
      pneumoniae. We report a case of a immunocompetent child affected by encephalitis
      caused by Mycoplasma pneumoniae.

PMID- 18710064
TI  - [Hydrological indications in the therapy of pharyngitis].
AB  - Pharyngitis is an inflammatory disease of the mucosal and submucosal structures
      of the throat. Infection may or may not be a component of the disease.
      Pharyngitis is one of the common illness for which patients visit primary care
      physicians. Most of them are diagnosed by clinical evaluation and usually respond
      to treatment with antibiotics, but exceptions occur when pharyngitis is caused by
      non bacterial inflammatory processes like virus, mycoses, reflux of gastric
      juices, tobacco or alcohol abuse. In these cases, as alternative and preventive,
      could be indicated the thermal therapy. For many centuries thermal waters have
      been used in the treatment of chronic inflammations of the upper respiratory
      airway, such as pharyngitis, with good results. Different thermal waters are
      currently used, in particular sulfur or sulfur- salty- bromine-, iodine- or
      sulfur-sulfate-bicarbonate-carbonate alkaline or sulfur-arsenical-ferruginous,
      normally utilized by inhalation or irrigation or aerosol-therapy. The principal
      pharmacological activity of these waters is connected to the concentrations of
      H2S, halogens (Iodine e Bromine), sulfates, arsenic and the level of
      radioactivity, concerning their antimicrobial power and the mucolytic effect of
      sulphur.

PMID- 18710065
TI  - [Etiology of sleep bruxism: a review of the literature].
AB  - Bruxism is a para-function with tooth clenching and grinding. Particularly, the
      sleep bruxism is a frequent phenomenon that causes cephalalgia and muscular/joint
      pains to the awakening, besides an increased dental abrasion and sensibility. The
      etiology of sleep bruxism is uncertain: while the occlusal discrepancies and the
      anatomy of the bony structures of the orofacial region play only a minor role,
      others factors, like smoking, alcohol, drugs, systemic diseases, stress, trauma
      and heredity, appear to have an important role in the sleep bruxism genesis.
      Recent polysomnographic studies, suggest that sleep bruxism episodes are part of
      an sleep arousal response. The sleep arousal response is a sudden change in the
      depth of sleep. Besides the sleep bruxism appears to be an disturbance in the
      dopaminergic system. Further psychological factors (like stress, anxiety) are
      implicated in the aetiology of sleep bruxism as well. The aim of this paper is to
      review the literature on the aetiology of bruxism.

PMID- 18710068
TI  - Editorial: leprosy research and current priorities in Ethiopia.

PMID- 18710069
TI  - The A9 study: the longest cohort study in the history of leprosy--an overview.

PMID- 18710070
TI  - Growth and development of children of mothers with leprosy and healthy controls.
AB  - INTRODUCTION: In the pre-sulphone and early sulphone years children of leprous
      parents had been followed in a few prospective studies to observe the development
      of leprosy. No studies were made of the growth and development of these children.
      METHODS: A prospective, open-ended, cohort study began in 1975 with follow-up of
      both mothers and their children until 2003. 156 pregnancies were studied
      consisting of 36 non-leprous (NL), 25 tuberculoid and borderline tuberculoid
      leprosy (TT&BT) (released-from-treatment), 18 with TT&BT (active), 42 borderline
      lepromatous leprosy (BL) and 35 lepromatous leprosy (LL). RESULTS: Babies of
      mothers with leprosy had lower birth weight, smaller placentae, grew more slowly,
      had more infections and higher infant mortality than those of non-leprous
      mothers. The findings were most marked in babies of LL mothers. Growth in
      childhood was uneventful, infants of LL mothers catching up by age 3.6 years.
      Childhood infections were common in all groups but more serious for children of
      lepromatous mothers. The puberty skeletal growth spurt, and, for the girls,
      menarche was delayed for children studied compared with a new healthy control
      group, with catch-up by late teens. These findings were most marked in children
      of lepromatous, especially LL, mothers. CONCLUSION: Impaired growth in utero and
      infancy is probably due to immunological factors but we could find no explanation
      for the delayed growth in adolescent children of LL mothers.

PMID- 18710071
TI  - Thermal threshold tester, a useful tool for detection of very early nerve damage-
      determination of normal values in a healthy population unexposed to Mycobacterium
      leprae and its application in the A9 study.
AB  - INTRODUCTION: In Ethiopia, a large percentage of leprosy patients present with
      established nerve damage. Present techniques for measuring nerve function
      impairment show no abnormality until 30% of nerve axons are destroyed. Nerve
      damage in leprosy occurs first in small diameter unmyelinated fibres, then in
      small myelinated fibres, and much later in large myelinated fibres. The Thermal
      Threshold Tester (TTT) was used to measure function in nerves carrying heat
      sensation (unmyelinated C fibres) and cold sensation (thinly myelinated Adelta
      fibres). PATIENTS: A school and community health survey, assessed 234 students
      and adults aged 10-75 years from Chencha Woreda, an area with low endemicity of
      leprosy. A group of students in Addis Ababa, exposed to leprosy, were also
      studied. RESULTS: The upper limits of normal were: wrist hot threshold (HT): 0.17
      degrees C, wrist cold threshold (CT): 0.19 degrees C, foot HT: 0.17 degrees C and
      foot CT: 0.20 degrees C. Both the leprosy group and also controls in Addis Ababa
      showed significantly increased TTT values. CONCLUSION: The TTT detects nerve
      damage before clinical neuritis occurs and is a valuable tool for early diagnosis
      of leprosy or detecting clinical relapse of treated patients and for sequential
      and quantitative monitoring of small diameter nerve function in other
      neuropathies.

PMID- 18710072
TI  - Facial burning in women with leprosy, physiological or pathological?
AB  - INTRODUCTION: Eight peri-menopausal women, five with borderline lepromatous
      leprosy and three with borderline tuberculoid leprosy, self-referred complaining
      of 'burning of the face. Four were seen in 1993, three having been treated as
      'menopausal'without betterment and four were seen in 1997. METHODS: Eight peri
      menopausal women who self-referred because of facial burning', and seven women
      who self-referred for other problems had a careful review of clinical records and
      were assessed fully for leprosy including graded sensory skin testing of the
      face, and standard nerve function tests. RESULTS: On examination three in each
      group of four complaining of facial burning were found to have major loss of
      facial sensation and one had generalised neuritis without significant facial
      involvement. Treatment with antileprotics and steroids resulted in recovery of
      facial sensation, although one later became blind. Of the seven who self-referred
      without facial burning, five had no facial sensory loss and two had slight loss
      of facial sensation.

PMID- 18710073
TI  - Health profile of highland Ethiopians in a small town in the south-western part
      of the country.
AB  - BACKGROUND: In conjunction with an investigation of nerve function tests of
      highland Ethiopians in an area of low endemicity of leprosy for 25-30 years, a
      comprehensive health survey was performed. METHODS: We assessed 236 subjects, 118
      females and 118 males, 177 students and 59 adults (Others) aged 10-75 years from
      Chencha woreda. We used a detailed medical, personal and social history,
      anthropomorphic measurements and complete physical examination. RESULTS: We
      identified six areas of medical concern: Intestinal parasite and diarrhoeal
      diseases affected 62%, despite treatment of all students and symptomatic adults
      the recurrence rate was high; skin diseases/conditions affected 88%; eye
      injections affected 26%; dental decay affected 33%; 20% had hypertension 14%
      requiring treatment; 11% gave a personal and/or family history of tuberculosis,
      44% gave a history of BCG immunisation, while 34% had BCG scars, the lowest
      percentage (11%) being in students from Daramallo woreda. RECOMMENDATIONS:
      Supplies of clean water, effective disposal of human excreta and control of flies
      would greatly reduce intestinal, skin and eye infections. Regular tooth cleaning
      and possibly fluoridation of drinking water should improve dental health, with
      diet and exercise for young hypertensives. BCG immunisation in Chencha and
      Daramallo woredas (inaccessible areas) needs urgent attention.

PMID- 18710074
TI  - Peripheral nerves and nerve function in highland Ethiopians.
AB  - INTRODUCTION: In Ethiopia, where leprosy has been one of the commonest causes of
      peripheral nerve enlargement and dysfunction, nerve functions are assessed by a
      battery of "physical" tests. Voluntary Muscle Test (VMT) and Graded Sensory Skin
      Test (STG) are standard tests used for persons with leprosy. Normal values for
      nerve function tests (NFT) in Highland Ethiopians have not previously been
      determined, but have been taken from standard textbooks. In this study, normal
      values for NFT were determined by VMT, STG, 2-Point Discrimination Tests both
      static and moving, and Thermal Threshold Test. Physiological enlargement of right
      ulnar and radial-cutaneous nerves has been recognised by some leprologists, but
      we were unable to find written records in the available medical literature.
      MATERIALS: We assessed 236 students and adults aged 10-75 years from Chencha
      Woreda, an area with low endemicity of leprosy for 25-30 years. Two affected by
      leprosy were excluded from the analysis. RESULTS: NFT thresholds were affected
      variously by age, exercise and skin factors, domicile and exposure to organo
      phosphates. Nerve size was affected by age, gender, exercise, skin fold
      thickness, body mass index. Exercise related physiological nerve enlargement has
      been documented. CONCLUSION: These data provide a usefull baseline for
      investigation of peripheral nerve function in highland Ethiopians.

PMID- 18710076
TI  - [Migraine--a burden for the individual and the society].
AB  - According to World Health Organization migraine is ranked among the first 20
      disorders in the world that cause significant disability. The economic burden due
      to migraine is significant; direct costs include visits to general practitioner
      and emergency department, costs of hospitalization and pharmacotherapy. Indirect
      costs comprise 2/3 of total costs and include absenteeism from work and costs due
      to reduced productivity. Reasons for the high economic burden are primarily
      insufficient diagnosing of migraine, the lack of information in the general
      population, underdevelopment of healthcare system and non-existence of plans and
      programms for a systematic approach in the management of headaches. Triptans as a
      specific and very efficient therapy for migraine are available on the market;
      studies have shown a high benefit-to-cost ratio when triptans were introduced as
      an acute therapy of migraine attacks. More attention should be paid to better
      diagnosis and treatment of headaches, especially migraine. We propose the main
      aspects for improvement of healthcare for patients with headaches.

PMID- 18710075
TI  - [Evidence based guidelines for the treatment of primary headaches].
AB  - Some patients suffering from headache require neurologic examination. The
      objective of the guidelines for the treatment of headaches is to help physicians
      in their daily care for headache patients. In most patients, the diagnosis of
      migraine has not been made by a physician and they have not received appropriate
      care to treat migraine attacks. New therapeutic methods (for acute and preventive
      treatment) have been introduced in the past fifteen years. Triptans should be
      offered to patients that fail to respond to usual analgesics, those with moderate
      to severe migraine in particular. Depending on comorbidity, preventive therapy
      should be recommended to individuals with frequent or prolonged migraine attacks.
      In patients with tension headaches, organic causes underlying the headache should
      be ruled out, while the treatment includes pharmacological and non
      pharmacological measures. Although rare, patients with cluster headaches suffer
      severe pain; oxygen inhalation or triptans are recommended for acute attack, and
      preventive therapy may be indicated in some cases. The guidelines provide
      classification, diagnostic criteria and therapeutic principles for primary
      headaches. All recommendations listed in the guidelines are based on meta
      analyses and recommendations from the world literature, with special reference to
      therapeutic options available in Croatia.

PMID- 18710077
TI  - [Migraine and the influence of hormones].
AB  - According to clinical observations, "pure" menstrual migraine refers to migraine
      attacks that occur exclusively 2 days from menstruation onset. AIM: The aim of
      this study was to determine the prevalence of menstrual migraine in a group of
      patients (N=289) attending a headache clinic; modification of migraine
      characteristics during pregnancy was also determined. RESULTS: Study results
      showed "pure" menstrual migraine to be present in 52 (18.0%) patients; 73 (25.3%)
      patients reported their migraine attacks to be always related to menstruation,
      yet also suffering attacks at other times; 95 (32.9%) patients stated that their
      migraine attacks were sometimes related to menstruation; and 121 (41.9%) patients
      observed no such relationship. In a subgroup of patients that had given birth to
      a child (n=145), migraine occurred for the first time in pregnancy in 14 (9.66%),
      improved or disappeared in 96 (66.2%), and worsened in 14 (9.66%) patients,
      whereas 21 (14.48%) patients reported no change in the character or frequency of
      migraine. CONCLUSION: Menstrual migraine is present in a high percentage of
      migraine patients. During pregnancy, migraine improves in the majority of
      patients while in a minority of patients migraine occurs for the first time or
      even worsens. The results of this study should serve as a basis to improve health
      care for patients with menstrual migraine.

PMID- 18710078
TI  - [Prevention of tension type headache with topiramate].
AB  - AIM: The aim of this study was to assess the efficacy of topiramate in the
      prevention of tension type headache. Tension type headache is the most common
      primary headache; the 1-year prevalence is 38%. Tension type headache often
      causes reduced quality of life. SUBJECTS AND METHODS: In this study 51 patients
      were included; the dose of topiramate was gradually increased to 100 mg and
      patients were followed up for 6 months. The number of days and decrease in
      headache intensity were measured by the Visual Analog Scale (VAS) from 1 to 10
      before and with therapy. RESULTS: Study results showed a statistically
      significant decrease in the number of days with headache: the mean number of days
      before therapy was 13.25 and with therapy 8.65, (p=0,0001). A statistically
      significant decrease in headache intensity was also observed by VAS scale: before
      therapy 6.27 and with therapy 3.33 (p=0.0001). CONCLUSION: This study showed
      topiramate to be efficient in the prevention of tension type headache.

PMID- 18710079
TI  - [Efficiency of pharmacological treatment of chronic post-traumatic headaches].
AB  - BACKGROUND: Chronic post-traumatic headache (CPH) is a complex clinical entity.
      The clinical features of CPH are variable and may resemble those of primary
      headaches (migraine, tension-type headache or cluster headache), as well as of
      cervicogenic headache. Therefore, the treatment must be individualized according
      to the headache type. There were few studies addressing the effectiveness of
      pharmacological treatment in patients with CPH. AIM: The aim of the present study
      was to analyze the efficiency of pharmacological treatment with analgesic drugs
      and concomitant psychotropic drugs in outpatients with CPH. METHODS: We studied
      59 outpatients with CPH (39 males and 20 females, mean age 36+/-13 years) who
      were taking analgetic monotherapy for their headache (simple analgesics, NSAIDs,
      atypic analgesics and triptans in subjects with migraine) and in case of comorbid
      psychic disorders some of them were taking psychotropic drugs. The efficiency of
      drug therapy was evaluated by the outcome scale based on the patients' headache
      diaries (outcome graded as improved, unchanged or worsened). RESULTS: Most of the
      study patients reported that their CPH was unchanged. The improvement was greater
      in the subgroup of cervico-occipital headache sufferers, but it was not
      statistically significant when compared to other subgroups. Post-traumatic
      migraine was the type of headache most refractory to drug therapy. The patients
      who took analgesics without psychotropic drugs had a reliably (p<0.05) better
      improvement of their headache. CONCLUSION: Analgesic drug monotherapy did not
      produce favorable therapeutic response in patients with CPH. Appropriate
      psychopharmacotherapy should be prescribed to CPH patients with psychiatric
      comorbidity.

PMID- 18710080
TI  - [Craniofacial neuralgias].
AB  - Craniofacial neuralgias are characterized by sudden paroxysmal pain along the
      distribution of one or more of the cranial or upper cervical spinal nerves. The
      most significant neuralgia of the craniofacial region is trigeminal neuralgia,
      while geniculate neuralgia, glossopharyngeal neuralgia and occipital neuralgia
      are less common. Trigeminal neuralgia may be primary or secondary. Idiopathic
      trigeminal neuralgia or tic douloureux has been recognized for centuries as an
      extremely painful disorder most commonly involving the maxillary nerve. Recurrent
      lancinating, shocklike unilateral pain lasting for seconds to minutes is provoked
      by non noxious stimulation of the skin at specific sites around the face and less
      frequently by movement of the tongue. The trigger zones are usually within the
      same dermatome as the painful sensation. After each episode, there is usually a
      refractive period during which stimulation of the trigger zone will not induce
      pain. Idiopathic trigeminal neuralgia occurs somewhat more frequently in women
      and usually begins in individuals 50 to 70 years of age. There is no pain between
      attacks, and the frequency of painful episodes can range from several per day to
      only a few per year. With time, the features may become more atypical, with
      greater areas of more enduring and dull pain and occasionally bilateral pain,
      rarely on both sides simultaneously. No sensory or reflex deficit is detectable
      by routine neurologic testing. Diagnostic local anesthetic blocks will identify
      the specific nerves involved and the trigger point distribution. Neurologic and
      neuroradiologic examination is advised in all cases to rule out diseases such as
      intracranical tumors, vascular malformations or multiple sclerosis.

PMID- 18710081
TI  - [Triptans--pivotal event in migraine treatment].
AB  - Introducing serotonin 5-HT1B/1D agonists in the migraine treatment in the early
      1990s had for the first time set guidelines for targeting a hypothetic
      physiologic source of the sequence of events in migraine, and results thus
      achieved were considerably better than those accomplished with earlier
      nonselective pharmacological approach. Triptans have revolutionized migraine
      management and inspired many epidemiological and public health surveys,
      strengthened efforts in understanding pathophysiology of migraine and initiated
      synthesis of many similar drugs in the triptan group, the first being
      sumatriptan. Triptans have risen to a therapeutic challenge posed by migraine,
      successfully thwarting the cycle of pain. In treating migraine sufferers,
      physicians can choose among seven triptans with different attributes. Each
      patient merits individualized approach in the treatment of migraine with
      triptans. Choosing the right triptan for a given patient is a matter of first
      matching the appropriate formulation to the patient, then deciding which agent
      will best meet the patient's needs. This process requires thorough understanding
      of the patient, careful and accurate assessment of the efficacy of previous
      medications used in acute care, and analysis of the individual features of the
      triptans being considered.

PMID- 18710082
TI  - [Temporomandibular disorders and headaches].
AB  - Temporomandibular disorder (TMD) is a common name for a series of pathologic
      conditions with similar signs and symptoms, which can lead to a disturbed and
      altered function of the stomatognathic system. Most of these conditions are of a
      multifactorial etiology, which can pose difficulties in obtaining a precise and
      accurate diagnosis. However, TMD is an ever more common and serious problem in
      contemporary dental practice and at general medical offices, so a more systematic
      approach in its diagnosis including data collection and interpretation is
      necessary. Accordingly, accurate diagnosis of TMD requires proper identification
      and classification of the dysfunction, as well as recognition of the mechanism
      and origin of pain occurrence.

PMID- 18710083
TI  - [Neurophysiological methods in headache diagnosis].
AB  - Neurophysiological methods used in the diagnosis of headache, especially migraine
      are: electroencephalography (EEG), evoked cortical potentials (VEP, BAER, ERP),
      reflex responses, autonomic tests and transcranial magnetic stimulation (TMS).
      Interpretation of EEG can be important for the differential diagnosis of some
      disorders with headache as a presenting symptom. Noninvasiveness, accessibility
      and ability to repeat the test due to exposure to harmful ionization are the main
      advantages of EEG. The role of thorough medical history and clinical assessment
      in patients with headache should not be underestimated. Interictal EEG (between
      headache attacks) is not significant in routine evaluation of these patients, but
      can be useful in patients with unusual symptoms suggesting epilepsy or migraine.
      It is indicated in patients with an abrupt onset of headache, in patients with
      migraine followed by neurological signs, in basilar migraine, migraine with
      extended duration of aura and in cases where epilepsy is suspected. Headache as a
      symptom is present in various brain and systemic diseases and metabolic
      disorders. EEG changes seen in headache patients are not specific for a
      particular disorder, but can suggest additional evaluation and accelerate
      accurate diagnosis and earlier treatment. Visual evoked cortical potentials (VEP)
      and cognitive evoked potentials (ERP) in patients with migraine in interictal
      periods have shown differences in sensory processing between patients with
      headache and healthy controls. Neurophysiological methods (VEP, ERP) between
      migraine attacks show cortical hyperactivity and predisposition for further
      attacks. Brainstem auditory evoked responses (BAER) are a sensitive method for
      the detection of central nervous system damage. Activation of the brainstem
      during the migraine attack results in an amplitude increment seen soon after the
      end of the attack. According to recent studies, R2 component of the blink reflex
      was six times longer during migraine attack as compared to interictal values.
      This is thought to be a response to sensitization of the skin nociceptive
      afferent arch or other neurons in the trigeminal nucleus. In patients with
      cluster headache, autonomic tests generate cardiovascular and pupillary response
      suggesting systemic sympathetic hyperactivation connected to concurrent pupillary
      sympathetic hypofunction and modified opioid modulation. TMS is shown to be very
      useful for the detection of pathophysiological changes of numerous disorders
      including migraine, due to its excitatory and inhibitory effects. Recent studies
      have shown changes in motor and occipital cortex during TMS interictal
      excitability. Neurophysiological tests are used in differential diagnosis of
      headache, follow up of possible complications in patients with symptomatic
      headache as well as in neurorehabilitation. In addition, electrophysiological
      diagnostic test can contribute to better understand the headache pathophysiology.

PMID- 18710084
TI  - [Migraine, stroke and patent foramen ovale--connected or not?].
AB  - A relationship between migraine with aura and patent foramen ovale (PFO) has been
      established in clinical studies, and is now related to previous observation that
      migraine and stroke are connected. Studies have shown that the prevalence of PFO
      in patients with migraine is about 2.5-fold than in patients without migraine. Up
      to now, there is no consensus on the treatment of PFO in primary or secondary
      prevention, so both surgical and conservative methods are used. Most
      nonrandomized studies (and 1 randomized placebo-controlled study) have shown that
      migraine attacks are reduced after PFO closure; however, recent studies show that
      a new onset or worsening of migraine headaches may occur after closure of PFO or
      atrial septal defects. Therefore, no definite conclusions can be made on the
      treatment of migraines by PFO closure.

PMID- 18710085
TI  - [Tension-type headaches].
AB  - Tension-type headache is one of the most common and most significant primary
      headaches. Tension-type headache is a very heterogeneous disorder. It can be
      divided into episodic and chronic tension-type headache. The pain is a dull,
      pressing, tightening, typically band-like sensation. The pain is of non-pulsating
      quality, the location is bilateral, and there is no nausea, vomiting, phonophobia
      or photophobia. There are no prodromal symptoms or aura. The pain is mild to
      moderate and it does not aggravate with routine physical activities. Some
      patients have increased tenderness of pericranial muscles. Psychological factors
      are common in tension-type headache. Nitric oxide has an important role in the
      pathophysiology of chronic tension-type headache. Probably it promotes central
      sensitization and therefore increases nociception. In differential diagnosis of
      tension type-headache, all structural and metabolic diseases causing headache
      have to be ruled out, as well as all other primary headaches. All comorbid and
      coexistent states should also be considered. In the treatment of tension-type
      headache, pharmacological and non-pharmacological methods are employed.
      Analgesics, myorelaxants, anxiolytics and antidepressants are most commonly used,
      as well as physical therapy, massage, acupuncture, behavioral therapy and
      psychotherapy. Recently, the applications of botulinum toxin and acupuncture have
      been described in the treatment and prophylaxis of tension-type headache.

PMID- 18710086
TI  - [Ophthalmological causes of headache].
AB  - Ophthalmologic causes of headache represent a very complex and extensive problem,
      and very often differential diagnostic problem too. Many various reasons of
      headache can be caused by ophthalmologic diseases like those of anterior and
      posterior eye segments, acute and subacute angle closed glaucoma and orbital
      diseases. Headache can be caused by no or poor correction of the refraction
      anomalies. Ophthalmologic causes of headache are quite frequently connected with
      conditions that affect other body systems apart from the eyes, nervous and/or
      vascular system in particular. Although ophthalmologic examination very provides
      the clue in patients with headache, the diagnostic and therapeutic approach to
      the problem has to be interdisciplinary.

PMID- 18710087
TI  - [Cervicogenic headache].
AB  - The aim of this report is to give information on the definition, clinical
      characteristics and therapy of cervical headache with comprehensive guidelines
      for patients on daily living activities with cervical pain and headache. This
      information has been designed to help the patients understand of their disability
      and in learn how to protect themselves.

PMID- 18710088
TI  - [Pain and ischemic symptoms in craniocervical artery dissection].
AB  - Arterial dissections of craniocervical arteries are being increasingly identified
      due to the growing awareness of the clinical picture and advances in imaging
      technologies. During a one-year period, we observed 20 patients with
      craniocervical artery dissection at cerebrovascular laboratory. Clinical picture,
      localization of the dissection and follow up studies were analyzed. Twenty study
      patients were divided into four groups: in group 1, all 4 patients with common
      carotid dissection with or without aortic dissection presented with pain; in
      group 2 with internal carotid dissection, pain was present in 5 out of 11
      patients, ischemic symptoms in all 11 patients, and Horner syndrome or lower
      cranial nerve palsies in 3 of 11 patients; in group 3, all 4 patients with
      dissecting plaque were free from pain but had ischemic symptoms; and in group 4
      there was only one patient with isolated vertebral artery dissection who had no
      pain but presented with stroke. Pain was the most prominent symptom in patients
      with lower craniocervical artery dissection. Ultrasound enabled follow up of the
      dissection.

PMID- 18710089
TI  - [Airplane headaches--two new cases and a review of the literature].
AB  - We present two new cases of airplane headache and compare them with 13 cases
      described so far. The two new cases refer to a man and a woman, one each. The
      woman suffered from headache during the take off and throughout the flight, which
      is rarely encountered. The man had a typical airplane headache with accompanying
      symptoms, with the feeling of pressure in the left side of the head. Diagnostic
      treatment revealed no pathomorphological substrate of the condition. The etiology
      and pathophysiology of this type of headache have not yet been fully clarified.
      We presume that this type of headache may be connected with changes in the nasal
      mucous membrane with deviation of the nasal septum, as well as in ethmoidal
      sinuses and other paranasal cavities. The rise of atmospheric pressure in the
      airplane and barotrauma from activation of the trigeminovascular system certainly
      play a major role in the occurrence of this headache.

PMID- 18710090
TI  - [Headache caused by pesticides--a review of the literature].
AB  - Headache makes one of the most common side effects of frequently pesticide
      application. This is to be taken care of in rural areas. Headaches have been
      reported with the use of ivermectin, ivermectin-diethylcarbamazine,
      organophosphates, and also with the fungicide maneb and copper sulfate,
      carbofuran, hexonal, dioxin, methomyl and its salts, as well as rare cases of
      poisoning with the fungicide combination of propineb and cymoxanil. Headache
      often occurs after long term work with pesticides and/or in laboratories. There
      are numerous symptoms accompanying headache in pesticide poisoning the most
      common being elevated body temperature, lassitude, dizziness, irritability,
      nausea, vomiting, epigastric pain, diarrhea, myalgia, pains in the arms and legs,
      sleepiness, pains in joints, irritation of eyes/face/skin, sweating. Much less
      common are respiratory disturbances, tachycardia, tachypnea and other cardiac
      distur bances, fall of blood pressure, gastrointestinal discomforts,
      constipation, poor appetite, significant decrease in leukocyte count, anemia,
      albuminuria, azotemia, fasciculations, miosis, blurred vision, memory
      disturbances and other neurologic disturbances, postural tremor, signs of
      cerebral function damage, bradykinesia, etc.

PMID- 18710091
TI  - [Recommendations for treatment of neuropathic pain].
AB  - Tricyclic antidepressants (TCAs), selective serotonin and norepinephrine reuptake
      inibitors (SSNRIs), calcium channel alpha2-delta ligands and topical lidocaine
      are recommended as a first-line treatment for patients with neuropathic pain. In
      patients who have failed to respond to these first-line medications alone or in
      combination, opioid analgetics or tramadol can be used as a second-line treatment
      alone or in combination with one of the first-line medications. In some specific
      situations, opioid analgetics or tramadol can also be considered for first-line
      use.

PMID- 18710092
TI  - [Diagnostic procedures in pediatric migraine].
AB  - The "gold standard" in the diagnosis of pediatric migraine includes personal
      history, clinical and neurological examination. Many important data on previous
      morbidity, psychosocial status and recent sickness (today's headache) can be
      found by using an interview, "face to face", or by "headache diary". On clinical
      examination, it is important to pay due attention to cardiovascular and
      respiratory systems as well as to examination of the skin. Thorough neurological
      examination may reveal disturbances of the mental status, cranial nerves, motor
      and sensory systems, reflexes, coordination and visual status. Acute headache
      without febrile illness and neurological disturbances is very indicative on
      childhood migraine or "migraine variants". However, due to many secondary
      headaches with migraine-like symptoms, it is important to perform detailed
      diagnostic protocol including computerized tomography, magnetic resonance
      imaging, electroencephalography, transcranial color doppler, laboratory tests and
      toxicological screening. Neuroimaging is indicated in children with acute
      headache, chronic progressive headache, especially if associated with vomiting,
      nausea or neurological disturbances, papillary edema, and in children with
      personality changes, learning difficulties and those under five years of age.

PMID- 18710093
TI  - Effects of earthworm (Pheretima sp.) on three sequential ryegrass harvests for
      remediating lead/zinc mine tailings.
AB  - Farm soil and artificial soil were mixed separately with Pb/Zn mine tailings and
      placed in the ratios (w/w) of 0, 12.5, 25, and 50% in pots, together with 0.33 g
      KH2PO4 and 0.35 g urea/pot. Each pot contained 15 ryegrass seedlings (Lolium
      multiflorum) and 7 earthworms (Pheretima sp.). At the end of the experiment
      (after the third harvests of ryegrass), the earthworms were all found to be alive
      and burrowed completely at the bottom of the pots in all treatments. Earthworm
      activity increased plant biomass significantly in artificial soil/tailings
      mixtures in the second and third harvests as compared with the control (without
      addition of earthworms), but not in the farm soil/tailings mixture. The biomass
      of ryegrass in both soil/tailings mixtures decreased with increase of tailings,
      especially those containing 50% tailings. In general, the plant biomass obtained
      from farm soil/tailings mixtures was lower than that from artificial
      soil/tailings mixtures. Earthworm activity did not significantly increase DTPA
      extracted Zn or Pb, in both soil/tailings mixtures. However, the concentrations
      in farm soil/tailings mixtures were lower in the second and third harvests,
      compared with the first harvest. The Zn and Pb uptake by ryegrass shoots in the
      two soils/tailings mixtures did not increase significantly (compared with the
      control) in the first and second harvests. However, in the third harvest, Zn and
      Pb uptake increased significantly in farm soil/tailings mixtures, but decreased
      significantly in artificial soil/tailings mixtures (compared with the control).
      The results indicated that the presence of earthworms and sequential plant
      harvesting could be a viable strategy for the remediation of Pb/Zn tailings.

PMID- 18710094
TI  - Identification of As accumulation plant species growing on highly contaminated
      soils.
AB  - Soils from the alluvial flats of the Turia River, Valencia, Spain, which were
      highly contaminated by decades of industrial activity, were surveyed for native
      plant species that could be candidates useful in phytoremediation. Concentrations
      of heavy metals and arsenic (As) in soils reached 25,000 mg Kg(-1) Pb, 12,000 mg
      Kg(-1) Zn, 70 mg Kg(-1) Cd, and 13500 mg Kg(-1) As. The predominant vegetation
      was collected and species identified. Soil samples and the corresponding plant
      shoots were analyzed to determine the amount of As accumulated by the various
      plant species. Several were able to tolerate more than 1000 mg Kg(-1) As in the
      soil. Bassia scoparia (Chenopodiaceae) survive in soil with 8375 mg Kg(-1) As.
      Arsenic accumulation in shoots of the various plant species investigated ranged
      from 0.1 to 107 mg Kg(-1) dw. Bassia scoparia (Chenopodiaceae), Inula viscosa
      (Asteraceae), Solanum nigrum (Solanaceae), and Hirschfeldia incana (Brassicaceae)
      had the highest values for As accumulation.

PMID- 18710095
TI  - Effect of cellulose wastes upon the growth of Phragmites australis.
AB  - Growth responses of Phragmites australis (Cav.) Trin. Ex Steud, (reed grass), a
      helophyte species, were examined under in vitro and greenhouse conditions in the
      presence of various residues from a Kraft pulp mill. Plant tolerance to solid
      residues (ashes, dregs, flyashes, grits, primary sludge, and brown stock rejects)
      was tested in vitro. Solid residues were added separately up to 30% (w/v), as
      well a liquid residue up to 30% (v/v), to a Murashige and Skoog (1962) sucrose
      free nutrient media with (5 mg l(-1)) 6-benzylaminopurine. After 2 mo in vitro,
      plantlets developed well in the presence of up to 10% solid or liquid wastes, but
      higher concentrations of either limited growth. This effect was mainly attributed
      to the plant's uptake and accumulation of various elements such as sodium, iron,
      copper, manganese, and boron, which are common to these waste types, thus showing
      an efficient phytoremediation potential. When added to MS media, the
      concentration of these elements generally decreased in the residual media after 2
      mo of culture: the initial sodium, iron, and copper content in the growth media
      was reduced ca. 10-fold detected; a 5-fold reduction occurred for manganese and
      boron. In experiments under greenhouse conditions with in vitro propagated
      plantlets potted in mixtures of a commercial organic soil and residues,
      significant differences in plant development (plant size and fresh weight
      increase) were observed in the presence of ashes mixed at levels of 20% and 30%,
      compared to the control in organic soil. For other solid wastes, plant growth was
      inhibited as the concentration of each waste increased, causing chlorosis and/or
      plant necrosis.

PMID- 18710096
TI  - Petroleum-degrading microbial numbers in rhizosphere and non-rhizosphere crude
      oil-contaminated soil.
AB  - Phytoremediation can be a cost-effective and environmentally acceptable method to
      clean up crude oil-contaminated soils in situ. Our research objective was to
      determine the effects of nitrogen (N) additions and plant growth on the number of
      total hydrocarbon (TH)-, alkane-, and polycyclic aromatic hydrocarbon (PAH)
      degrading microorganisms in weathered crude oil-contaminated soil. A warm-season
      grass, sudangrass (Sorghum sudanense (Piper) Stapf), was grown for 7 wk in soil
      with a total petroleum hydrocarbon (TPH) level of 16.6 g TPH/kg soil. Nitrogen
      was added based upon TPH-C:added total N (TPH-C:TN) ratios ranging from 44:1 to
      11:1. Unvegetated and unamended controls were also evaluated. The TH-, alkane-,
      and PAH-degrading microbial numbers per gram of dry soil were enumerated from
      rhizosphere and non-rhizosphere soil for vegetated pots and non-rhizosphere soil
      populations were enumerated from non-vegetated pots. Total petroleum-degrading
      microbial numbers were also calculated for each pot. The TH-, alkane-, and PAH
      degrading microbial numbers per gram of dry soil in the sudangrass rhizosphere
      were 3.4, 2.6, and 4.8 times larger, respectively, than those in non-rhizosphere
      soil across all N rates. The presence of sudangrass resulted in significantly
      more TH-degrading microorganisms per pot when grown in soil with a TPH-C:TN ratio
      of 11:1 as compared to the control. Increased plant root growth in a crude oil
      contaminated soil and a concomitant increase in petroleum-degrading microbial
      numbers in the rhizosphere have the potential to enhance phytoremediation.

PMID- 18710097
TI  - Phytofiltration of arsenic-contaminated groundwater using Pteris vittata L.:
      effect of plant density and nitrogen and phosphorus levels.
AB  - This field-scale hydroponic experiment investigated the effects of plant density
      and nutrient levels on arsenic (As) removal by the As-hyperaccumulator Pteris
      vittata L. (Chinese brake fern). All ferns were grown in plastic tanks containing
      30 L of As-contaminated groundwater (130 microg x L(-1) As) collected from South
      Florida. The treatments consisted of four plant densities (zero, one, two, or
      four plants per 30 L), two nitrogen (N) concentrations (50% or 100% of 0.25
      strength Hoagland solution [HS]), and two phosphorous (P) concentrations (15% and
      30% of 0.25 strength HS). While low P was more effective than high P for plant As
      removal initially, N levels showed little effect. At 15% P, it took 3 wk for the
      ferns at a plant density of four to reduce As to less than 10 microg L(-1) (USEPA
      and WHO standard), whereas it took 4-6 wk at plant densities of one or two. For
      reused ferns, established plants with more extensive roots than "first-time"
      ferns, a low plant density of one plant/30 L was more effective, reducing As in
      water to less than 10 microg L(-1) in 8 h. This translates to an As removal rate
      of 400 microg h(-l) plant(-1), which is the highest rate reported to date.
      Arsenic-concentration in tanks with no plants as a control remained high
      throughout the experiment. Using more established ferns supplemented with dilute
      nutrients (0.25 HS with 25% N and 15% P) with optimized plant density (one plant
      per 30 L) reduced interplant competition and secondary contamination from
      nutrients, and can be recommended for phytofiltration of As-contaminated
      groundwater. This study demonstrated that P. vittata is effective in remediating
      As-contaminated groundwater to meet recommended standards.

PMID- 18710099
TI  - Responsibility in the operating theatre: the guidelines are still controversial.

PMID- 18710098
TI  - Effect of a polycyclic aromatic hydrocarbon on the phytoremediation of zinc by
      two plant species (Brassica juncea and Festuca arundinacea).
AB  - The redevelopment of contaminated land is becoming increasingly necessary under
      sustainable- development legislation; however, many of the contaminated sites are
      "orphan" sites and therefore require a low-cost remediation technology. These
      sites often contain a cocktail of pollutants including organics and inorganics.
      Phytoremediation provides a possible solution, but there is little information
      available on the tolerance of plant species to multiple pollutants and their
      ability to remediate in mixed-contaminant soils. The effect of a polycyclic
      aromatic hydrocarbon (pyrene) in soil upon the remediation of zinc by Brassica
      juncea and Festuca arundinacea was investigated under normal climatic conditions
      in the United Kingdom. Zinc was effectively removed from mixed-contaminant soils
      in the presence of both species, in comparison to a control treatment. Both
      species accumulated zinc in plant tissues in the presence of pyrene, but the
      growth of B. juncea was significantly reduced when zinc and pyrene were supplied
      in combination. Zinc was predominantly associated with root tissues for F.
      arundinacea, whereas B. juncea contained higher concentrations in shoot tissues.
      F. arundinacea provides a possible species to be used for the phytoremediation of
      brownfield sites, but further research is required to determine a range of
      species that may be used and their applicability to different contaminants.

PMID- 18710100
TI  - Appraisal era for endovascular repair of abdominal aortic aneurysms.

PMID- 18710101
TI  - The evidence for stenting in femoropopliteal occlusive disease.

PMID- 18710102
TI  - Current concepts in breast reconstruction.
AB  - As the incidence of breast cancer increases, breast reconstruction is more and
      more often proposed and its indications are viewed in terms of quality of life.
      In the past, delayed reconstruction was the rule. Progress in reconstructive
      techniques currently allows performing immediate reconstruction in selected
      cases, even when the operative field has to be irradiated. These new techniques
      generally improve the result of breast reconstruction. Moreover, expansion of
      screening techniques allows detection of small tumors for which a conservative
      excision is sufficient. Nevertheless, this kind of less aggressive surgery may
      require a reconstructive procedure in order to maximise the aesthetic result.

PMID- 18710103
TI  - Abdominal surgery during pregnancy: a retrospective study of 23 patients.
AB  - OBJECTIVE: The aim of this study was to demonstrate that during pregnancy a large
      variety of non-gynaecological abdominal pathologies can be safely managed with
      surgery. METHODS: The medical records of twenty-three patients that were pregnant
      and underwent open or laparoscopic surgery from 1997 to 2007 were reviewed.
      RESULTS: Twenty-one of the 23 patients have given birth and all but one of the
      babies were healthy with normal weights, sizes, and APGAR scores. One patient had
      spontaneous termination of pregnancy one week after the surgical procedure and
      one patient is out of follow-up. Preterm partus was induced in three patients due
      to life-threatening conditions for the mother. Each laparoscopy was performed
      safely without peri-operative complications. CONCLUSION: Open or laparoscopic
      abdominal surgery poses little or no additional risk for mother or child.

PMID- 18710104
TI  - The prognosis of patients operated on for gastric cancer in relation to the
      percentage of lymph nodes invaded by tumour.
AB  - INTRODUCTION: In evaluating the type of gastrectomy and lymphadenectomy for
      gastric cancer, adequate prognosis has been dependant on the retrieval of at
      least 15 lymph nodes. We propose an alternative method in which the prognostic
      value is evaluated, according to whether or not more than 20% of the retrieved
      lymph nodes are invaded by tumour. MATERIALS & METHODS: Sixty-five patients (36
      men, 29 women) with a median age of 69 years (mean age 68.9 +/-12.1 years) were
      evaluated, who were operated upon between 1985 and 1999 for gastric cancer by
      gastrectomy with either D1 or D2 lymphadenectomy. RESULTS: The average number of
      retrieved lymph nodes was 10.4 +/- 8.6. In 51 patients (78.5%) less than 15 and
      in 14 patients (21.5%) 15 or more lymph nodes were retrieved, according to the
      TNM guidelines. In our study, there is a statistically significant difference in
      prognosis between patients with less than 20% and those with more than 20% of the
      retrieved lymph nodes invaded by tumour, irrespective of the total number of
      lymph nodes resected. CONCLUSION: Gastric cancer patients in whom less than 20%
      of the retrieved lymph nodes are invaded, have a significantly better prognosis
      compared with patients in whom 20% or more of the lymph nodes retrieved are
      invaded by tumour, irrespective of the total number of retrieved lymph nodes.

PMID- 18710105
TI  - Results of biofeedback therapy together with electrical stimulation in faecal
      incontinence with myogenic lesions.
AB  - Reports about biofeedback therapy together with electrical stimulation with
      faecal incontinence are rare. This study is to investigate the effectiveness of
      biofeedback therapy in faecal incontinence patients with myogenic lesions.
      METHODS: One hundred and twenty-six patients with faecal incontinence caused by
      myogenic lesions were referred to this programme, comprising three sessions of
      supervised therapy in hospital followed by 2 months of home exercise. Biofeedback
      therapy methods that consist of strengthening muscles biofeedback, sensory
      discrimination biofeedback, synchronizing biofeedback, and electrical stimulation
      were selected to improve the programme. Clinical scores and outcomes of the
      anorectal function were assessed before and after the programme, and t test was
      performed for statistical analysis. RESULTS: Before this programme, there were 19
      patients with good clinical scores, 46 patients with fair and 61 patients with
      poor clinical scores. After therapy, 98 patients achieved good scores, 24
      patients fair, and only four patients had poor clinical scores. The squeeze
      pressure and the sphincter electromyography amplitude were improved
      significantly, the rectal sensory threshold was decreased significantly, and 80
      patients who previously had no external anal sphincter reflex acquired such a
      reflex. At the two-year follow-up, 60.2% (65/108) of patients maintained the
      clinical outcomes. CONCLUSION: biofeedback therapy together with electrical
      stimulation is an effective method for faecal incontinence in patients with
      myogenic lesions. Patients should be offered this choice of therapy.

PMID- 18710106
TI  - Is there an increased incidence of surgically removed thyroid carcinoma in
      Belgium ten years after Chernobyl? A study of hospital discharge data.
AB  - In order to provide some answers to the much debated subject of the consequences
      of the Chernobyl accident, this study attempts to measure the incidence of
      surgically removed thyroid cancers in Belgium ten years following the explosion.
      The analysis was made from the hospital discharge data between 1993 and 1998. It
      offers the advantage of national coverage in spite of certain validity limits.
      The results show an increase in surgically removed thyroid cancers, which is not,
      however, evident in the more susceptible younger generation who were involved at
      the time of the accident. Furthermore, the geographic distribution of the
      incidence is more marked in the south of the country, unaffected by the
      radioactive iodine contamination of 1986, which was more prevalent in the east of
      the country. The study of the type of surgery involved shows a rise in the
      proportion of total thyroidectomies. These findings are in favour of the
      hypothesis of a causal effect linking the increased incidence of thyroid cancers
      to medical practice and surgery in particular and not to the consequence of the
      possible contamination.

PMID- 18710107
TI  - Thymoma: surgical results of 73 cases.
AB  - PURPOSE: Thymomas are uncommon tumours; they represent a broad spectrum of
      morphological and clinical behaviour. The purpose of this study is to identify
      the factors that influence survival. METHOD: Seventy-three patients with thymoma
      who underwent thymectomy between 1980 and 2002 were reviewed. Prognostic factors
      assessed were: age, sex, presenting symptoms, histological features, stage at
      diagnosis and extent of surgical resection. RESULTS: Complete resection was
      achieved in 67 patients and incomplete in 6. Survival rates of patients in the
      1st or 2nd stages were 100% and 92.8% for 10 years, respectively. A high
      incidence of myasthenia gravis (MG) associated thymomas (80.8%) was found. These
      patients had better survival rates when compared to non-myasthenic patients.
      However the mortality rate for malign thymomas was high (65.7%) due to tumoral
      invasion. The histological types of thymoma did not influence the survival rate.
      CONCLUSIONS: The association of MG with thymoma enables earlier detection of
      tumour, thus higher survival rates were achieved in these patients. Survival was
      also related to the stage of the tumour at diagnosis and the completeness of
      resection.

PMID- 18710108
TI  - The incidence of familial nonmedullary thyroid cancer in a large case series.
AB  - PURPOSES OF THE STUDY: In contrast to familial medullary carcinoma, familial
      nonmedullary thyroid carcinoma (FNMTC) is less frequent and has been less
      investigated. The aim of this study was to determine the frequency of FNMTC and
      analyse the main demographic and clinical characteristics of the patients.
      MATERIAL AND METHODS: Data on 1411 patients surgically treated for nonmedullary
      thyroid carcinoma, in the Center for Endocrine Surgery in Belgrade, from 1995 to
      2006 were analysed. The possible presence of malignant tumours of the thyroid
      gland was investigated in their closest relatives in order to identify cases of
      FNMTC. Only data on first-degree relatives (parents and children) and second
      degree relatives (grandparents, grandchildren and siblings) were taken into
      account in the analysis. RESULTS: Thirteen patients (11 females and 2 males)
      (0.92% of those with nonmedullary carcinoma of the thyroid gland) had a familial
      form of the disease. In five families two members had a tumour, and in one family
      three members. In five out of six families it was a papillary carcinoma and in
      one family a follicular carcinoma. Patient age varied from 20 to 79 years, with a
      mean age of 40 years. The tumour size ranged from 5 to 60 mm (mean 25 mm). In two
      of the thirteen cases the tumour penetrated the capsule of the thyroid gland. In
      four cases the tumour was multicentric and bilateral, and in a further two
      metastases were present in regional lymph nodes. During the follow-up period,
      which lasted from 2 to 12 years (mean 8.5 years), two relapses were detected.
      CONCLUSION: Familial nonmedullary carcinoma of the thyroid gland occurs very
      rarely.

PMID- 18710109
TI  - Interlocking nailing of forearm fractures.
AB  - AIM OF THE STUDY: The aim of this retrospective study is to evaluate the results
      after treating diaphyseal fractures of the radius and ulna with an interlocking
      intramedullary nail. MATERIALS AND METHODS: Between 2001 and 2005, 78 patients
      with 118 fractures were treated using the ForeSight intramedullary nail (Smith &
      Nephew, Memphis, USA). The average patient age was 37.02 years. In the
      postoperative period, early and late complications were evaluated through
      radiological and functional methods. The average period of follow-up was 25
      months (range: 12-58 months). RESULTS: The average length of time to demonstrated
      bone healing was 14.2 weeks. Four cases of prolonged healing were observed.
      Pseudo-arthrosis formation did not occur. Assessment of function according to
      Anderson gave the following results: full range of movement in 88.6% of patients;
      mild restriction of movement in 10.1%; severe restriction of movement in 1.3% of
      patients. The implanted material was extracted from 27 patients. Refractures did
      not occur. Postoperative complications included: 1 superficial infection, 3 cases
      of incomplete radio-ulnar synostosis; one case of compartment syndrome.
      CONCLUSIONS: Upon comparing the techniques of using plates with those of nailing
      in the treatment of forearm fractures, we have achieved comparable results with
      nailing. We therefore regard it as advantageous, in particular for treating open,
      serial and grossly comminuted fractures of the forearm bones.

PMID- 18710110
TI  - Spontaneous rectus sheath hematoma: a case report.
AB  - Spontaneous rectus sheath hematoma is an uncommon condition which usually
      presents as acute abdomen, mimicking other abdominal disorders. Management must
      be initially conservative, but surgery is indicated in progressive hematomas. We
      present a case report of rectus sheath hematoma conservatively managed.

PMID- 18710112
TI  - A rare cause of ileus: invagination due to ectopic pancreas.
AB  - INTRODUCTION: Invagination is seen rarely as a cause of ileus in adults. The
      cause of invagination in children differs from that in adults. In adults it is
      mostly due to organic lesions (tumour). CASE REPORT: In a 49 years old patient,
      with 3 months of intermittant abdominal pain, radiologic investigations suspected
      a of small bowel tumour. The patient was operated on. At exploration, there was
      an ileo-ileal invagination on the terminal ileum over 40 cm distance A totally
      necrosed ileum segment was resected and an end-to-end anastomosis was performed.
      Inside the excised ileal loop their was a polyp-like lesion originating from
      submucosa, bordered by the wall but not protruding to the lumen. The pathological
      examination of the lesion revealed ectopic pancreatic tissue between the muscular
      layers of the bowel wall. RESULT: Intestinal invagination must be got in mind as
      a rare cause of ileus in adults. During it's clinical course their is enough time
      to reach the diagnosis. So unnecessory resections and postoperative complications
      can be prevented.

PMID- 18710111
TI  - Ischaemic caecal necrosis.
AB  - Isolated ischaemic caecal necrosis is an unusual event. Because right colon
      location is less frequent than left one, it may not be considered in the
      differential diagnosis of right lower quadrant pain. With the typical symptoms
      (right-sided abdominal pain and tenderness), patients are suspected of having
      either appendicitis or caecal carcinoma. CT-scan images of caecal wall thickening
      are often misinterpretated as acecal neoplasm or abscess. We present a case of
      isolated ischaemic caecal necrosis misinterpretated as a caecal neoplasm.

PMID- 18710114
TI  - The importance of cyst fluid analysis for differentiation of pancreatic cyst.
AB  - Cystic abnormalities of the pancreas encompass a wide variety of lesions ranging
      from the non-malignant pseudo-cyst to neoplastic lesions. Although cystic
      neoplasms of the pancreas are rare, differentiation is important in determining
      the proper treatment. A 55-year-old female presented with a cystic abdominal
      mass. Her computed tomography scan showed a cystic mass of 102 x 99 x 97 mm which
      was well-circumscribed and homogeneous with few thin septations and mild contrast
      enhancement of the fibrous wall located in the body of the pancreas. Percutaneous
      diagnostic aspiration of the cyst fluid was performed under ultrasonic guidance
      for proper diagnosis and management, which revealed a CEA greater than 200 ng/ml
      (0-3) and amylase within normal limits 30 U/L (< or = 100). High CEA and normal
      amylase values supported the diagnosis of mucinous cystadenoma rather than pseudo
      cyst. With these findings, the patient underwent distal pancreatectomy with
      splenectomy. Pathological analysis revealed a mucinous cystadenoma of the
      pancreas. This report is a confirmation that cyst fluid analysis can provide a
      pre-operative classification of these diagnostically difficult lesions.

PMID- 18710113
TI  - Negative fluid balance in patients with abdominal compartment syndrome--case
      reports.
AB  - Abdominal compartment syndrome (ACS) is defined as a sustained increase of intra
      abdominal pressure (IAP) above 20 mmHg followed by the development of organ
      dysfunction. Treatment of ACS is still a question to be discussed and surgical
      decompression is usually preferred. According to recent data, massive crystalloid
      resuscitation of shock plays a key role in the development of secondary ACS in
      trauma patients. As mentioned previously, a high volume of infused crystalloids
      and a positive fluid balance were associated with ACS development in trauma
      patients as well as in septic patients. Moreover, we observed that a treatment
      strategy based on the achievement of a negative fluid balance resulted in a
      dramatic decrease in IAP and an improvement in haemodynamics and ventilation.
      This approach has been indicated as an interesting option for non-surgical
      treatment, with a caution that such intervention may exacerbate gut
      hypoperfusion. In this report we present two patients with secondary ACS
      development following abdominal surgery in which the achievement of a negative
      fluid balance showed a similar effect. Moreover, the fluid removal procedure also
      seemed to be associated with an improvement in splanchnic perfusion, as measured
      by gastric tonometry.

PMID- 18710115
TI  - A mucinous cystadenoma in the mesentery of the right hemicolon.
AB  - Cysts of the mesentery, retroperitoneum and omentum are rare. We present a
      patient with a mucinous cystadenoma in the mesentery of the right hemicolon. The
      exact aetiology of these cysts at the aforementioned sites is still unclear.
      Adenocarcinomas can arise in mucinous cystadenomas. Therefore, in our opinion, to
      prevent spillage the right approach is to primarily perform a laparatomy instead
      of attempting to remove these lesions laparoscopically, even if clinical and
      radiological signs of malignancy are absent.

PMID- 18710116
TI  - Submucosal lipoma of the ascending colon as a source of massive lower gastro
      intestinal bleeding: a case report.
AB  - Colonic lipomas are relatively uncommon lesions. They have been documented as the
      source of massive low gastro-intestinal bleeding in only five previous reports in
      the English language literature. We report an extremely rare case of massive
      haemorrhage caused by an ascending colon submucosal lipoma and review the
      pathophysiology, diagnosis and management.

PMID- 18710117
TI  - Intestinal perforation due to phytobezoar obstruction: a case report.
AB  - Phytobezoars are uncommon causes of acute abdomen. We report a patient who
      presented with acute abdomen and who was intra-operatively diagnosed as having a
      small intestinal perforation due to an intestinal phytobezoar.

PMID- 18710118
TI  - Plexus injury after reduction of anterior caudal dislocation of the shoulder.
AB  - The case is reported of a 45-year-old male patient who fell when his ladder
      slipped away from underneath him. He sustained a bilateral dislocation of the
      shoulders (bilateral luxatio erecta humeri). The injury on one hand was a
      glenohumeral dislocation of the humerus head right to ventral and caudal,
      accompanied by a suspected fracture of the tuberculum major and on the other hand
      a glenohumeral dislocation of the left humerus head to ventral and caudal,
      accompanied by a suspected total collum fracture. Based on this case and the
      pertinent literature, the patho-physiology, diagnosis and treatment of this rare
      injury are discussed. After immediate closed reduction, soft tissue damage,
      fractures or neurovascular lesions should be operated on as soon as possible.

PMID- 18710119
TI  - Concerning: laparoscopic inguinal hernia repair.

PMID- 18710120
TI  - The history of pancreas transplantation: past, present and future.
AB  - The first attempt to cure type 1 diabetes by pancreas transplantation was done at
      the University of Minnesota, in Minneapolis, on December 17, 1966, followed by a
      series of whole pancreas transplantation. Due to the lack of potent
      immunosuppressive drugs, rejections and infections, it was concluded that
      pancreas was less antigenic than the kidney which was less antigenic than the
      duodenum. It opened the door to a period, between the mid 70's to mid 80's where
      only segmental pancreatic grafts were used in the recipient. Numerous techniques
      for diverting or dealing with the pancreas juice secretion were described, none
      of them being satisfactory. In the late 70's - early 80's, three major events
      happened and boosted the development of pancreas transplantation: firstly the
      introduction of Cyclosporine A in the clinical field, secondly the organization
      on March 1980, of the first international meeting on Pancreas Transplantation
      with the first report of the International Pancreas Transplantation Registry
      (IPTR) and finally in 1982, the organization of the first informal so-called
      Spitzingsee meetings where pancreas transplantation successes but mainly failures
      were discussed which precluded the onset of IPITA (International Pancreas and
      Islet Transplantation Association), EuroSPK (European Study Group for
      simultaneous Pancreas and Kidney Transplantation) and EPITA (European Pancreas
      and Islet Transplantation Association). During one of the Spitzingsee meetings,
      participants had the idea to renew the urinary drainage technique of the exocrine
      secretion of the pancreatic graft with segmental graft and eventually with whole
      pancreaticoduodenal transplant. That was clinically achieved during the mid 80's
      and remained the mainstay technique during the next decade. In parallel, the
      Swedish group developed the whole pancreas transplantation technique with enteric
      diversion. It was the onset of the whole pancreas reign. The enthusiasm for the
      technique was rather moderated in its early phase due to the rapid development of
      liver transplantation and the need for sharing vascular structures between both
      organs, liver and pancreas. During the modern era of immunosuppression, the whole
      pancreas transplantation technique with enteric diversion became the gold
      standard for simultaneous pancreas and kidney transplantation (SPK), with portal
      drainage of the venous effluent of the pancreas, even for pancreas after kidney
      (PAK) or pancreas transplantation alone (PTA). Today, there remains room for
      improvement: safety of using the duodeno-duodenal anastomosis technique must be
      confirmed by prospective analysis while preventing ischemic reperfusion injuries,
      using specific drugs; that must be assessed in new trials.

PMID- 18710121
TI  - Antibiotics save lives--but bacteria are inevitable.

PMID- 18710123
TI  - Sterility matters.

PMID- 18710124
TI  - Infection control and prevention in perioperative practice.
AB  - The personal and financial consequences of avoidable infection are enormous in
      personal and global terms (DH 2003, Stone, Larson & Kawar 2002). Patients expect
      to be treated and cared for in clean conditions, and not be exposed to the risks
      of acquiring an infection by poor practice on the part of healthcare workers (DH
      2005, Health Care Commission 2005). Infection control and prevention in
      perioperative settings assumes an even greater significance because of the
      vulnerability of patients who are already ill or injured, and because surgery,
      anaesthesia and immediate postoperative recovery may expose them to invasive
      procedures, allowing more portals of entry for infection. There is ample
      evidence, widely available, to support best practice in all healthcare settings.
      The methods are cheap, easy to apply and very effective (Wright 2004, Pratt et al
      2007). This article will examine a range of evidence applicable to perioperative
      infection control and prevention, including an assessment of current practice and
      how it may be improved, with a particular emphasis on surgical site infection
      associated with Meticillin Resistant Staphylococcus Aureus (MRSA) and Clostridium
      Difficile (C.diff).

PMID- 18710125
TI  - Feedback from members on decontamination services.
AB  - In February 2007 AfPP asked its members for their feedback on decontamination
      services. For example, decontamination services to perioperative areas and issues
      experienced on a daily basis, particularly service issues from those outsourced
      services. AfPP asked its members to share their experiences, concerns and issues 
      both positive and negative.

PMID- 18710126
TI  - Decontamination: back to basics.
AB  - My invitation from this Journal's Editor, Felicia Cox, to provide a paper for
      this themed issue, included the sentence 'I was wondering if you or a colleague
      would like to contribute a back to basics article on the relevant standards and
      guidelines for decontamination, including what is compliance?'. The reason it is
      so interesting to me is that the term 'back to basics' implies reverting to a
      simpler time in life - when by just sticking to the rules, life became easier.
      However, with decontamination this is not actually true.

PMID- 18710127
TI  - Decontamination in the dental setting.
AB  - With these factors taken into account it should be feasible to implement the best
      possible decontamination solution for any dental practice (hopefully opting for
      the two-room layout). With the correct equipment, facilities and fully trained
      and educated staff, today's general dental practice will be able to move forward
      in full compliance with the latest regulations and be ready for inevitable future
      changes in the law.

PMID- 18710128
TI  - Instrument integrity and sterility: the perioperative practitioner's
      responsibilities.
AB  - Surgical instruments, whether single use or reusable, are defined by the
      University of Newcastle's Online Medical Dictionary as 'Hand held tools or
      implements used by health professionals for the performance of surgical tasks'
      (CancerWEB 1998). This definition, in its broadest terms, recognises that the
      inter-professional team (health professionals) are involved in the use, care and
      management of that tool or implement (performance of surgical tasks). Spry (2007)
      identifies that a surgical instrument could last 10 years if well made, carefully
      handled and appropriately used and that it is the responsibility of the surgical
      team and sterile services personnel to preserve and protect the life of each
      individual instrument. This article will identify the perioperative
      practitioner's responsibility in ensuring that each surgical instrument is fit
      for purpose, safe for use and will not harm the patient during use. The article
      will outline the process of instrument/set selection and the pre-, intra- and
      postoperative checks that should be made by the inter-professional team prior to,
      during and after use of that set/instrument. This article will also enable the
      practitioner to gain or reinforce their knowledge and understanding of the
      decontamination process and its application within the perioperative environment.

PMID- 18710129
TI  - Prion disease transmission: can we apply standard precautions to prevent or
      reduce risks?
AB  - Prion diseases present unique challenges to healthcare facilities, both in the
      care and treatment of patients. A significant cause for concern is in the routine
      reprocessing of medical devices used on patients and how disease transmission can
      be prevented on the reuse of devices. Investigations have shown that prion
      disease can be transmitted on medical devices, which can be a concern given the
      long incubation times associated with these diseases and that guidelines to
      control transmission only really apply in a small number of known or at risk
      cases. It is only recently that medical device-associated cleaning, disinfection
      and sterilization technologies have been investigated and the results of these
      studies are summarized in this report. The evidence would suggest that many
      simple decontamination steps can be applied to dramatically reduce the risks to
      patients, but the research has also given some surprises. Overall, it is
      reasonable to expect that standard precautions will be able to be applied both
      today as well as in the future to reduce the risk of prion disease transmission
      as well as the many other human pathogen concerns, although this may mean changes
      in some of our practices.

PMID- 18710130
TI  - Surgical dressings and turbulent years of cotton industry.
AB  - Everyday use of a simple cotton bud should remind us of our not so distant past
      and of the appalling trade in people. Harvesting this precious commodity required
      forced labour eventually leading to a key turning point in the history of
      surgery, as civil war raged in America during the 1860s. The fight to end slavery
      was to reveal a new weapon against disease and certain death. A material used in
      this struggle against wound infection was the available stockpiles of redundant
      cotton. Once boiled to make softer, its use on patients in military hospitals
      proved to be the first clinical application of sterile surgical dressings.

PMID- 18710131
TI  - Photoangiolytic laser treatment of early glottic cancer: a new management
      strategy.
AB  - The 532 nm pulsed KTP (potassium titanyl phosphate) laser and the 585 nm pulsed
      dye laser (PDL) are photoangiolytic lasers that have been demonstrated to be
      effective for managing vocal fold dysplasia. The putative mechanism of action is
      selective photoangiolysis of the sublesional microcirculation. On the basis of
      this experience, early glottic cancers were treated by selectively targeting the
      intralesional and sublesional microvasculature. This approach was derived from
      Folkman's concepts of neoplastic growth resulting from tumor angiogenesis. Staged
      microlaryngeal treatment was adopted, because it facilitated optimal functional
      results, and was considered safe, because early glottic cancer rarely
      metastasizes. Furthermore, intercurrent disease during conventional incremental
      radiotherapy is typical in treating early glottic cancer. A pilot group of 22
      patients with early glottic cancer (13 T1, 9 T2) were treated with a fiber-based
      angiolytic laser. Eleven of the 22 had unilateral disease and were entirely
      treated by laser photoangiolysis as a sole modality. Eleven of the 22 had
      bilateral disease; 5 of the 11 were treated entirely (bilaterally) by laser
      photoangiolysis, and 6 of the 11 only underwent laser treatment of the less
      involved vocal fold, with conventional resection being done on the dominant side
      of the cancer. The initial 8 of the 22 were treated with the PDL, and the latter
      14 of the 22 were treated with the pulsed KTP laser. No patient has cancer
      presently, and none have undergone posttreatment radiotherapy or open surgery.
      The mean follow-up is 27 months, 13 of the 22 patients have at least 2 years of
      follow-up, and the first patient was treated just over 5 years ago. Objective
      measures of vocal function revealed that photoangiolytic treatment of early
      glottic cancer resulted in significant postoperative improvements despite the
      fact that half of the patients had bilateral disease. Angiolytic lasers
      effectively involuted early glottic cancer, with microsurgically directed
      nonionizing radiation of the dense neoplastic blood supply resulting in complete
      tumor regression. This approach is conceptually attractive, because it is
      repeatable, it preserves all conventional cancer treatment options, and it
      results in excellent vocal function by improving phonatory mucosal wave
      vibration. Observations from this investigation suggest that this new and novel
      cancer treatment strategy is effective; however, larger patient cohorts, longer
      follow-up, and multi-institutional confirmation will be necessary to establish
      incontrovertible oncological efficacy.

PMID- 18710133
TI  - Evaluating, diagnosing, and treating sleep disorders.

PMID- 18710132
TI  - 'To sleep, perchance to dream'.

PMID- 18710134
TI  - A newborn male with possible Hirschsprung's disease.

PMID- 18710135
TI  - A 2-year-old male with developmental delay, irritability, and failure to thrive.

PMID- 18710136
TI  - The snoring child.
AB  - Snoring is a common manifestation of obstructive sleep apnea and represents one
      end of the spectrum of sleep-related breathing disorders. Children with primary
      snoring initially may develop OSAS later, so inquiring about symptoms of OSAS
      should be part of each visit. Obstructive sleep apnea can result in serious
      cardiovascular and metabolic consequences and neurocognitive deficits.
      Adenotonsillar hypertrophy remains the most common cause of OSA although the
      rising prevalence of obesity is of increasing importance. Polysomnography remains
      the gold standard in the diagnoses of OSAS and in assessing the risks associated
      with surgery. Most children with OSAS can be treated with adenotonsillectomy in
      the ambulatory surgery center. However, there are children at risk for severe
      OSAS and for postoperative complications, who will need PICU care. In addition to
      adenotonsillectomy, OSAS can be treated successfully in referral centers with
      other surgical approaches and by the use of positive airway pressure. Children
      with obesity-related OSAS often require CPAP or BPAP for control of OSAS.

PMID- 18710137
TI  - Evaluating children who seize during sleep.

PMID- 18710138
TI  - Disorders of arousal in children.
AB  - Disorders of arousal from NREM sleep are common events in childhood. Although
      they are considered to be benign in most cases, recurrent events may be
      associated with other primary sleep disorders or psychiatric comorbidities. It is
      important to ensure that the child achieves adequate sleep and receives treatment
      for primary sleep disorders. If the events are particularly disruptive or
      frequent, both behavioral and pharmacologic treatments are available.

PMID- 18710139
TI  - Circadian rhythm disorders in pediatrics.

PMID- 18710140
TI  - Taking a pediatric sleep history.
AB  - Sleep problems in children are common, can be persistent and recurrent, can lead
      to significant health issues, and usually affect other family members as well as
      the child. There is an AAP guideline to at least screen for snoring. Sleep
      deprived children often present with different symptoms than sleep-deprived
      adults. Improving a child's sleep can help the child and their family function
      better during the day. As in other areas of medicine, getting an accurate and
      thorough history narrows down the possible etiologies and guides the subsequent
      evaluation.

PMID- 18710141
TI  - Leveraging knowledge management to our advantage.

PMID- 18710142
TI  - Cost optimization of integrated wastewater drainage and treatment systems.
AB  - This paper presents the cost optimization of an urban drainage and wastewater
      treatment system. The mixed sewer urban drainage (including combined sewer
      overflows and retention basins), the activated sludge wastewater treatment plant
      (WWTP), and the permissible loading of the receiving water were optimized
      simultaneously by the nonlinear programming approach. For this purpose, the
      integrated optimization model OPTIMALWWT was developed. The economic objective
      function of the defined investment and operational costs is subjected to rigorous
      design and ecological constraints. A practical example of the cost optimization
      of an existing urban drainage and WWTP, located in Slovenia, is presented to
      demonstrate the efficiency of the proposed method. For each of the two different
      design approaches, three different optimization cases were carried out for three
      different technological alternatives. As a result, the optimal technological
      process was finally selected for the reconstruction of the system, as a result of
      its suitable costs and operational safety.

PMID- 18710143
TI  - Pathogen and indicator organism reduction through secondary effluent filtration:
      implications for reclaimed water production.
AB  - The reduction of pathogens and indicator organisms through secondary effluent
      filtration was investigated at six full-scale treatment facilities, ranging in
      capacity from 0.04 to 1 m3/s (1 to 25 mgd). Grab samples were assayed for
      pathogens (cultivable enteric viruses, Giardia, and Cryptosporidium) and
      indicator organisms (coliforms, enterococci, Clostridium perfringens, and
      coliphages) quarterly under peak flow conditions from each facility over the
      course of 1 calendar year. Log10 removals resulting from filtration averaged 0.3
      to 0.8 log10 for cultivable enteric viruses, 0.4 to 1.5 log10 for protozoan
      parasites, 0.01 to 3.7 log10 for indicator bacteria, and 0.3 to 1.1 log10 for
      coliphages. In addition to filter design (cloth, monomedium shallow- or deep-bed,
      or dual-media filters), differences in reduction of pathogens and indicators
      could be attributed to the combined effects of hydraulic loading rates, chemical
      addition practices, backwashing and postbackwashing operating strategies, and the
      effectiveness of upstream biological treatment and sedimentation.

PMID- 18710144
TI  - Endosulfan sulfate sorption on natural organic substances.
AB  - This work proposes a viable remediation method based on the use of natural
      organic substances (NOSs) that characterize the Mediterranean region to improve
      the ecological system. A series of experiments, including variable conditions,
      such as temperature, pH, contact time, and pesticide concentration, were
      performed to demonstrate the efficiency of endosulfan sulfate removal from water
      by NOSs. Experimental results showed that the pH and temperature of pesticide
      solutions negatively affect the adsorption process. The maximum adsorption
      capacity for a specific initial concentration of endosulfan sulfate (0.5
      microg/L) was achieved with Origanum compactum (75%), followed by Cistus
      ladaniferus and Raphanus raphanistrum (72 and 68%, respectively). The adsorption
      tests gave very satisfying results and point to the possible application of these
      supports as a remediation technique to prevent pesticide contamination of aquatic
      ecosystems.

PMID- 18710145
TI  - Enhanced biological phosphorus removal and recovery.
AB  - Activated sludge systems designed for enhanced nutrient removal are based on the
      principle of altering anaerobic and aerobic conditions for growth of
      microorganisms with a high capacity of phosphorus accumulation. Most often,
      filamentous bacteria constitute a component of the activated sludge microflora.
      The filamentous microorganisms are responsible for foam formation and activated
      sludge bulking. The results obtained confirm unanimously that the filamentous
      bacteria have the ability of phosphorus uptake and accumulation as
      polyphosphates. Hydrodynamic disintegration of the foam microorganisms results in
      the transfer of phosphorus and metal cations and ammonium-nitrogen into the
      liquid phase. It was demonstrated that the disintegration of foam permits the
      removal of a portion of the nutrients in the form of struvite.

PMID- 18710146
TI  - Improved computational model (AQUIFAS) for activated sludge, integrated fixed
      film activated sludge, and moving-bed biofilm reactor systems, part II:
      multilayer biofilm diffusional model.
AB  - Research was undertaken to develop a diffusional model of the biofilm that can be
      applied in lieu of a semi-empirical model to upgrade an activated sludge system
      to an integrated fixed-film activated sludge (IFAS) or moving-bed biofilm reactor
      (MBBR) system. The model has been developed to operate with up to 12 cells
      (reactors) in series, with biofilm media incorporated to one or more of the zone
      cells, except the anaerobic zone cells. The values of the kinetic parameters for
      the model were measured using pilot-scale activated sludge, IFAS, and MBBR
      systems. The biofilm is divided into 12 layers and has a stagnant liquid layer.
      Diffusion and substrate utilization are calculated for each layer. The equations
      are solved simultaneously using a finite difference technique. The biofilm flux
      model is then linked to the activated sludge model. Advanced features include the
      ability to compute the biofilm thickness and the effect of biofilm thickness on
      performance. The biofilm diffusional model is also used to provide information
      and create a table of biofilm yields at different substrate concentrations that
      can be used in the semi-empirical model.

PMID- 18710147
TI  - Improved computational model (AQUIFAS) for activated sludge, integrated fixed
      film activated sludge, and moving-bed biofilm reactor systems, part III: analysis
      and verification.
AB  - Research was undertaken to analyze and verify a model that can be applied to
      activated sludge, integrated fixed-film activated sludge (IFAS), and moving-bed
      biofilm reactor (MBBR) systems. The model embeds a biofilm model into a multicell
      activated sludge model. The advantage of such a model is that it eliminates the
      need to run separate computations for a plant being retrofitted from activated
      sludge to IFAS or MBBR. The biofilm flux rates for organics, nutrients, and
      biomass can be computed by two methods-a semi-empirical model of the biofilm that
      is relatively simpler, or a diffusional model of the biofilm that is
      computationally intensive. Biofilm support media can be incorporated to the
      anoxic and aerobic cells, but not the anaerobic cells. The model can be run for
      steady-state and dynamic simulations. The model was able to predict the changes
      in nitrification and denitrification at both pilot- and full-scale facilities.
      The semi-empirical and diffusional models of the biofilm were both used to
      evaluate the biofilm flux rates for media at different locations. The biofilm
      diffusional model was used to compute the biofilm thickness and growth, substrate
      concentrations, volatile suspended solids (VSS) concentration, and fraction of
      nitrifiers in each layer inside the biofilm. Following calibration, both models
      provided similar effluent results for reactor mixed liquor VSS and mixed liquor
      suspended solids and for the effluent organics, nitrogen forms, and phosphorus
      concentrations. While the semi-empirical model was quicker to run, the
      diffusional model provided additional information on biofilm thickness, quantity
      of growth in the biofilm, and substrate profiles inside the biofilm.

PMID- 18710148
TI  - Feasibility of using microalgal biomass cultured in domestic wastewater for the
      removal of chromium pollutants.
AB  - The feasibility of obtaining and using the biomass of a microalga, Chlorella
      miniata, from domestic wastewater (DW) cultures for the removal of chromium(III)
      [Cr(III)] and chromium(VI) [Cr(VI)] was compared with that from commercial
      Bristol medium (BM). Results showed that Chlorella miniata cultured in DW under
      16-8 hours light-dark cycle [DW(16-8)] had similar growth to that in BM [BM(16
      8)], but these two biomass had different biochemical compositions, and the former
      one had lower carbohydrate and higher protein content. When cultured in domestic
      wastewater, a higher biomass was obtained under continuous illumination [DW(24
      0)], and the cells had higher carbohydrate and lower protein concentrations than
      that of DW(16-8). The spectra of the Fourier transform infrared spectrometer
      revealed that the functional groups on the surface of the three kinds of biomass-
      DW(16-8), DW(24-0), and BM(16-8)--were comparable, except an additional peak at
      1731 cm(-1) was found in the biomass cultured in domestic wastewater, which was
      probably the result of bacterial contamination. Although biochemical differences
      were found among the three kinds of microalgal biomass, similar biosorption
      performances to chromium pollutants were recorded, with approximately 75% Cr(III)
      and 100% Cr(VI) removed at equilibrium in Cr(III) and Cr(VI) experiments,
      respectively, when dead biomass was used as a biosorbent. Therefore, it is
      possible to culture Chlorella miniata in domestic wastewater and use the biomass
      for the removal of chromium pollutants.

PMID- 18710149
TI  - High-solids anaerobic digestion of municipal sludge pretreated by thermal
      hydrolysis.
AB  - High-solids anaerobic digestion can consistently achieve 55 to 60% volatile
      solids destruction after thermal hydrolysis pretreatment, which reduces its
      viscosity and increases the fraction of soluble organic matter. For feed sludge
      with total solids concentrations between 6.8 and 8.2%, the process is stable at
      hydraulic retention times of 9 to 12 days, significantly increasing the treatment
      capacity of existing digesters or, in treatment plants without spare capacity,
      helping to postpone, reduce, or even avoid costly infrastructure investments.
      Process stability is related to the high concentration of soluble organic matter
      in the digesters. High-solids temperature-phased digestion appears to be superior
      to high-solids mesophilic digestion, with respect to process flexibility and
      stability, biosolids stabilization, and biogas generation, although ammonia
      inhibition may have occurred. Implementation of high-solids digestion could
      significantly reduce operation and maintenance costs of solids-handling
      operations.

PMID- 18710150
TI  - Oxygen transfer in a full-depth biological aerated filter.
AB  - The City of San Diego, California, evaluated the performance capabilities of
      biological aerated filters (BAFs) at the Point Loma Wastewater Treatment Plant.
      The City conducted a 1-year pilot-plant evaluation of BAF technology supplied by
      two BAF manufacturers. This paper reports on the first independent oxygen
      transfer test of BAFs at full depth using the offgas method. The tests showed
      process-water oxygen-transfer efficiencies of 1.6 to 5.8%/m (0.5 to 1.8%/ft) and
      3.9 to 7.9%/m (1.2 to 2.4%/ft) for the two different pilot plants, at their
      nominal design conditions. Mass balances using chemical oxygen demand and
      dissolved organic carbon corroborated the transfer rates. Rates are higher than
      expected from fine-pore diffusers for similar process conditions and depths and
      clean-water conditions for the same column and are mostly attributed to extended
      bubble retention time resulting from interactions with the media and biofilm.

PMID- 18710151
TI  - [Insufficient strategy for Chlamydia control. A plan of action should motivate
      changed sexual behavior].

PMID- 18710152
TI  - [Not just a physician but a dad as well...].

PMID- 18710153
TI  - [With Care Choice in our time].

PMID- 18710154
TI  - [Clostridium difficile-associated diarrhea threatens the patient safety!].

PMID- 18710155
TI  - [Care Choice on its way in primary health care. Big differences between the
      models and high needs for development].

PMID- 18710156
TI  - [Parenteral drugs with similar names and packaging. A study shows a great risk of
      confusion].

PMID- 18710157
TI  - [Consequences of climate changes for the health status in Sweden. Heat waves and
      disease transmission most alarming].

PMID- 18710158
TI  - [Treatment of depression with light therapy. A systematic literature review. SBU
      summary and conclusions].

PMID- 18710159
TI  - [Unexpected adverse effect of benzodiazepines].

PMID- 18710160
TI  - [Champix not suitable for elderly with depression].

PMID- 18710161
TI  - [The National Board of Health and Welfare on diet advice to type 2 diabetics: no
      need to reconsider the directive].

PMID- 18710162
TI  - [Hospital mortality a bad indicator of patient safety in health care].

PMID- 18710163
TI  - [Establish social physician teams in vulnerable districts].

PMID- 18710164
TI  - [Appeal from ten associations of health professionals: the government must
      quality-assure clinical research].

PMID- 18710165
TI  - [Take-over for private health services: fall forward, but why discriminate
      general practice?].

PMID- 18710166
TI  - [Massive pulmonary embolism and patient safety. Do triage nurses have an adequate
      education?].

PMID- 18710167
TI  - [It was not quite that bad].

PMID- 18710168
TI  - [The documentary was not about ADHD].

PMID- 18710169
TI  - [Life-threatening hyponatremia as a sequelae of the false notion that water is
      beneficial for both the internal and the external beauty of human beings].

PMID- 18710170
TI  - [The drama "Woyzeck" is a valuable medical historical document].

PMID- 18710171
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on molar development among non
      resistant inbred strains of mice: a geometric morphometric analysis.
AB  - Prenatal development is highly sensitive to the effects of environmental
      contaminants. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental
      toxicant that at very low levels causes teratogenic effects such as irregular
      tooth development. Variations in susceptibility to TCDD's effects have been
      attributed primarily to differences at the Ahr locus. There is some evidence,
      however, that genes at other loci may be involved in mediating TCDD's effects on
      various endpoints. Our hypothesis therefore was that the effect of TCDD on molar
      development would differ even among inbred mouse strains possessing similar Ahr
      alleles. To test this, geometric morphometric techniques were used to evaluate
      the effects of several different levels of TCDD on molar size, shape and
      asymmetry in the offspring of dosed females from five different inbred strains of
      mice bearing TCDD-sensitive Ahr alleles. The results indicated that a maternal
      dose of 1 microg TCDD/kg body weight on gestation day 13 altered the shape (but
      not the size or asymmetry) of the first two molars in mice from the C3H/HeJ and
      CBA/J strains of mice, but not in mice from the other strains. The C3H/HeJ and
      CBA/J strains appeared to be the most sensitive to the disruption of molar
      development via TCDD and the C57BL/6J strain appeared to be the least sensitive.

PMID- 18710172
TI  - Regional differences in D/L aspartic acid ratios in the human mandible as a
      possible indicator of the bone remodeling rate.
AB  - In slowly metabolizing tissue such as tooth, bone and ocular lens, D-amino acids
      converted from L-amino acids accumulate with age and thus reflect the tissue
      turnover rate. To investigate whether D-amino acids play a role in determining
      the bone remodeling rate, we measured the accumulation of D-aspartic acid, which
      has the fastest rate of racemization, in various areas of the mandible. The level
      of D-aspartic acid was higher in the ramus than in the body (P < 0.01), and
      within the body, the level was higher in the basal area than in the alveolar area
      (P < 0.01). Within the alveolar area, the level of D-aspartic acid was higher in
      the molar region than in the incisal region (P: 0.05-0.01). No correlation was
      found between the accumulated level of D-aspartic acid with age, because all the
      specimens were obtained from elderly people with only a few years difference in
      age. There was also no correlation between D-aspartic acid and sex. In
      conclusion, we suggest that accumulation of D-aspartic acid in the mandibular
      bone reflects the differences in remodeling associated with occlusion. The
      incisal portion of the alveolar area of the mandible (above the mandibular
      canal), shows the greatest evidence of active remodeling.

PMID- 18710173
TI  - On the effect of cranial deformation in determining age from ectocranial suture
      closure.
AB  - Available techniques for determining age from human cranial remains are limited.
      This study examines the efficacy of Meindl and Lovejoy's (1985) method of
      determining age based on ectocranial suture closure patterns as compared to a
      baseline of ages developed from a multifactorial approach employing various age
      determining factors from across the skull. What makes this study different is
      that the sample upon which this comparison is performed contains a large number
      of artificially deformed crania. Our hypothesis is that aging techniques that
      rely on suture closure patterns as markers are complicated by the results of
      artificial modification of the cranial vault. The study is conducted on adult,
      human crania from prehispanic archaeological sites in South America. Results
      demonstrate a significant difference between the two aging methods, more
      particularly when applied to deformed skulls. We conclude that when a skull is
      deformed age should be estimated utilizing multiple factors that exclude Meindl
      and Lovejoy's ectocranial suture aging technique.

PMID- 18710174
TI  - Bone mass in First Nations, Asian and white newborn infants.
AB  - OBJECTIVE: To compare bone mass in newborn infants of First Nations, white and
      Asian mothers while accounting for vitamin D status. Fifty infants born healthy
      at term age were measured for bone mass using dual energy x-ray absorptiometry
      (DXA) within 15 days of life. Vitamin D status was measured as 25(OH)D in cord
      plasma. White infants were separated based on 25(OH)D concentrations into
      sufficient and insufficient (< 32.5 nmol/L) to match for vitamin D status of the
      Asian infants and the First Nations group. Differences among groups were tested
      using ANOVA and post hoc testing with Bonferroni multiple comparisons test. There
      were no differences in whole body, spine or femur BMC between the white
      sufficient and insufficient infants. However, the Asian infants had lower (P <
      0.01) spine BMC compared to the white infants and the First Nations infants were
      intermediate. No differences among the ethnic groups were observed for whole body
      or femur BMC. These data suggest that white and First Nations newborn infants
      have comparable bone mass. Asian infants have lower spine bone mass which is more
      than a factor of body size and independent of vitamin D status at birth.

PMID- 18710175
TI  - Accuracy of growth model parameters: effects of frequency and duration of data
      collection, and missing information.
AB  - This study was done to compare the accuracy of prediction of growth parameters
      using the Gompertz model when (1) data was collected infrequently, (2) data
      collection was truncated, and (3) data was missing. Initial growth rate and rate
      of decay were reduced by half when the model was fitted to data collected
      biweekly compared to data collected weekly. This reduction led to an increase in
      age of maximum growth and subsequently over-predicted the asymptotic body weight.
      When only part of the growth duration was used for prediction, both the initial
      growth rate and rate of decay were reduced. The degree of data truncation also
      affected sexual dimorphism of the parameters estimated. Using pre-asymptotic data
      for growth parameter prediction does not allow the intrinsic efficiency of growth
      to be determined accurately. However, using growth data with body weights missing
      at different phases of the growth curve does not seem to significantly affect the
      predicted growth parameters. Speculative or diagnostic conclusions on intrinsic
      growth should be done with data collected at short intervals to avoid potential
      inaccuracies in the prediction of initial growth rate, exponential decay rate,
      age of maximum growth and asymptotic weight.

PMID- 18710176
TI  - Why A-level evidence does not make it to clinicians' A-lists: the case of
      thromboprophylaxis in medical patients.

PMID- 18710177
TI  - A targeted, multifactorial intervention reduced mortality in patients with type 2
      diabetes and microalbuminuria.

PMID- 18710178
TI  - Metformin plus a lifestyle intervention was more effective than either alone for
      antipsychotic-induced weight gain.

PMID- 18710179
TI  - Nondiabetic maternal hyperglycemia was associated with adverse pregnancy
      outcomes.

PMID- 18710180
TI  - Metformin (alone or with insulin) was as effective as insulin for preventing
      perinatal complications in gestational diabetes.

PMID- 18710181
TI  - Review: erythropoiesis-stimulating agents increase mortality and venous
      thromboembolism in cancer-associated anemia.

PMID- 18710182
TI  - An automated external defibrillator in the home did not reduce mortality in
      patients at risk for cardiac arrest.

PMID- 18710183
TI  - Antihypertensive therapy with indapamide and perindopril reduced mortality in
      patients greater than or equal to 80 years.

PMID- 18710184
TI  - Risk for cancer was still increased over 2 years after stopping hormone therapy.

PMID- 18710185
TI  - Review: limited evidence suggests that statins are safe in patients with liver
      disease.

PMID- 18710186
TI  - Review: systemic corticosteroids, antibiotics, and noninvasive positive pressure
      ventilation are effective in acute COPD.

PMID- 18710187
TI  - Rapid screening for methicillin-resistant Staphylococcus aureus (MRSA) did not
      reduce MRSA acquisition rate.

PMID- 18710188
TI  - Melanoma of the scalp and neck had greater risk for melanoma-specific mortality
      than melanoma of the extremities.

PMID- 18710189
TI  - CO gas sensing by ultrathin tin oxide films grown by atomic layer deposition
      using transmission FTIR spectroscopy.
AB  - Ultrathin tin oxide films were deposited on SiO2 nanoparticles using atomic layer
      deposition (ALD) techniques with SnCl4 and H2O2 as the reactants. These SnO(x)
      films were then exposed to O2 and CO gas pressure at 300 degrees C to measure and
      understand their ability to serve as CO gas sensors. In situ transmission Fourier
      transform infrared (FTIR) spectroscopy was used to monitor both the charge
      conduction in the SnO(x) films and the gas-phase species. The background infrared
      absorbance measured the electrical conductivity of the SnO(x) films based on
      Drude-Zener theory. O2 pressure was observed to decrease the SnO(x) film
      conductivity. Addition of CO pressure then increased the SnO(x) film
      conductivity. Static experiments also monitored the buildup of gas-phase CO2
      reaction products as the CO reacted with oxygen species. These results were
      consistent with both ionosorption and oxygen-vacancy models for chemiresistant
      semiconductor gas sensors. Additional experiments demonstrated that O2 pressure
      was not necessary for the SnO(x) films to detect CO pressure. The background
      infrared absorbance increased with CO pressure in the absence of O2 pressure.
      These results indicate that CO can produce oxygen vacancies on the SnO(x) surface
      that ionize and release electrons that increase the SnO(x) film conductivity, as
      suggested by the oxygen-vacancy model. The time scale of the response of the
      SnO(x) films to O2 and CO pressure was also measured by using transient
      experiments. The ultrathin SnO(x) ALD films with a thickness of approximately 10
      A were able to respond to O2 within approximately 100 s and to CO within
      approximately 10 s. These in situ transmission FTIR spectroscopy help confirm the
      mechanisms for chemiresistant semiconductor gas sensors.

PMID- 18710190
TI  - High-resolution microwave spectroscopic and ab initio studies of propanoic acid
      and its hydrates.
AB  - High-resolution microwave spectra of the propanoic acid monomer (PPA) and two of
      its hydrates, the PPA-(H2O) and the PPA-(H2O)2, were recorded using a pulsed
      nozzle Fourier transform microwave spectrometer. The rotational and centrifugal
      distortion constants of these species were determined. Agreements between the
      experimental and ab initio results of these constants, and of the planar moment
      of inertia, the dipole moments, and the orientation of the PPA relative to the
      H2O confirm the geometry of the hydrates, i.e. H2O binds to the carboxylic group
      of PPA and forms hydrogen-bonded ring complexes. The equilibrium constant and the
      change of entropy and enthalpy for the formation of PPA-(H2O) were also derived,
      based on the calculation of partition functions, to evaluate the abundance of
      this monohydrate in the troposphere.

PMID- 18710191
TI  - Quantitative (upsilon, N, Ka) product state distributions near the triplet
      threshold for the reaction H2CO --> H + HCO measured by Rydberg tagging and laser
      induced fluorescence.
AB  - In this paper, we report quantitative product state distributions for the
      photolysis of H2CO --> H + HCO in the triplet threshold region, specifically for
      several rotational states in the 2(2)4(3) and 2(3)4(1) H2CO vibrational states
      that lie in this region. We have combined the strengths of two complementary
      techniques, laser-induced fluorescence for fine resolution and H atom Rydberg
      tagging for the overall distribution, to quantify the upsilon, N, and Ka
      distributions of the HCO photofragment formed via the singlet and triplet
      dissociation mechanisms. Both techniques are in quantitative agreement where they
      overlap and provide calibration or benchmarks that permit extension of the
      results beyond that possible by each technique on its own. In general agreement
      with previous studies, broad N and Ka distributions are attributed to reaction on
      the S0 surface, while narrower distributions are associated with reaction on T1.
      The broad N and Ka distributions are modeled well by phase space theory. The
      narrower N and Ka distributions are in good agreement with previous quasi
      classical trajectory calculations on the T1 surface. The two techniques are
      combined to provide quantitative vibrational populations for each initial H2CO
      vibrational state. For dissociation via the 2(3)4(1) state, the average product
      vibrational energy (15% of E(avail)) was found to be about half of the rotational
      energy (30% of E(avail)), independent of the initial H2CO rotational state,
      irrespective of the singlet or triplet mechanism. For dissociation via the
      2(2)4(3) state, the rotational excitation remained about 30% of E(avail), but the
      vibrational excitation was reduced.

PMID- 18710192
TI  - Hydrogen nuclear spin relaxation in hydrogen-ice clathrate.
AB  - H2 in D2O ice clathrate has been studied by hydrogen NMR. In a previous report,
      the H2 line shape was shown to be due to incompletely averaged intramolecular
      dipolar interactions. Here the relaxation times T1, T1rho, and T2 are reported.
      T1 passes through a minimum at 10 K, indicating that the rotational transition
      rate Gamma between the three sublevels of J = 1 passes through the resonance
      frequency at this temperature. On the cold side, T1 varies as T(-2.6); on the hot
      side, the rate T1(-1) varies as T(-2) plus a constant (due to paramagnetic
      impurities). These indicate a two-phonon process drives the rotational
      transitions Gamma. The spin-echo T2 is nearly independent of temperature and in
      reasonable agreement with the Van Vleck intermolecular H2-H2 second moment. T1rho
      deviates from the expected T1rho = T1 behavior above 85 K, revealing an
      additional slow-motion source of relaxation. The deviation is driven by the
      hopping of H2 between large cages. Ortho-para conversion is measured to be much
      slower in the clathrate than in the bulk solid, reflecting the greater distances
      between the H2 molecules.

PMID- 18710193
TI  - Intramolecular charge transfer with the planarized 4-cyanofluorazene and its
      flexible counterpart 4-cyano-N-phenylpyrrole. Picosecond fluorescence decays and
      femtosecond excited-state absorption.
AB  - The fluorescence spectrum of the rigidified 4-cyanofluorazene (FPP4C) in n-hexane
      consists of a dual emission from a locally excited (LE) and an intramolecular
      charge-transfer (ICT) state, with an ICT/LE fluorescence quantum yield ratio of
      Phi'(ICT)/Phi(LE) = 3.3 at 25 degrees C. With the flexible 4-cyano- N
      phenylpyrrole (PP4C) in n-hexane, such an ICT reaction also takes place, with
      Phi'(ICT)/Phi(LE) = 1.5, indicating that for this reaction, a perpendicular twist
      of the pyrrole and benzonitrile moieties is not required. The ICT emission band
      of FPP4C and PP4C in n-hexane has vibrational structure, but a structureless band
      is observed in all other solvents more polar than the alkanes. The enthalpy
      difference Delta H of the LE --> ICT reaction in n-hexane, -11 kJ/mol for FPP4C
      and -7 kJ/mol for PP4C, is determined by analyzing the temperature dependence of
      Phi'(ICT)/Phi(LE). Using these data, the energy E(FC,ICT) of the Franck-Condon
      ground state populated by the ICT emission is calculated, 41 (FPP4C) and 40
      kJ/mol (PP4C). These large values for E(FC,ICT) lead to the conclusion that with
      FPP4C and PP4C, direct ICT excitation, bypassing LE, does not take place. FPP4C
      has an ICT dipole moment of 15 D, similar to that of PP4C (16 D). Picosecond
      fluorescence decays allow the determination of the ICT lifetime, from which the
      radiative rate constant k'(f)(ICT) is derived, with comparable values for FPP4C
      and PP4C. This shows that an argument for a twisted ICT state of PP4C cannot come
      from k'(f)(ICT). After correction for the solvent refractive index and the energy
      of the emission maximum nu(max)(ICT), it appears that k'(f)(ICT) is solvent
      polarity-independent. Femtosecond transient absorption with FPP4C and PP4C in n
      hexane reveals that the ICT state is already nearly fully present at 100 fs after
      excitation, in rapid equilibrium with LE. In MeCN, the ICT state of FPP4C and
      PP4C is likewise largely developed at this delay time, and the reaction is
      limited by dielectric solvent relaxation, which shows that the ICT reaction is
      ultrafast, at the experimental time limit of 50 fs. PP4C and FPP4C have a similar
      planar ICT structure, without an appreciable twist of the pyrrole and
      benzonitrile subgroups. Their crystal structure is compared with calculations for
      the S0 ground state.

PMID- 18710194
TI  - Conformational changes in cryptophane having C1-symmetry studied by vibrational
      circular dichroism.
AB  - Vibrational circular dichroism (VCD) measurements and density functional theory
      (DFT) calculations were used to obtain the absolute configuration of a
      cryptophane molecule having C1-symmetry (labeled cryptophane-H). This molecule
      exhibits chiroptical properties different from those published for cryptophane-A
      having D3-symmetry [Brotin et al. J. Am. Chem. Soc. 2006, 128, 5533-5540]. In
      particular, we have shown that the conformation of the aliphatic linkers is very
      dependent on the solvent used and its ability to enter (CDCl3 solution) or not
      (C2D2Cl4 solution) in the cryptophane cavity. Calculations performed at the DFT
      (B3PW91/6-31G*) level establish, besides the absolute configuration, the
      preferential anti and gauche conformations of the aliphatic linkers of the
      chloroform@cryptophane-H complex and the empty cryptophane-H molecule,
      respectively. Polarimetric measurements performed in several solvents reflect
      also the change of conformation of the bridges upon guest encapsulation.

PMID- 18710195
TI  - A study of the hydrogen abstraction reactions of C2H radical with CH3CN, C2H5CN,
      and C3H7CN by dual-level generalized transition state theory.
AB  - The hydrogen abstraction reactions C2H + CH3CN --> products (R1), C2H + CH3CH2CN 
      -> products (R2), and C2H + CH3CH2CH2CN --> products (R3) have been investigated
      by dual-level generalized transition state theory. Optimized geometries and
      frequencies of all the stationary points and extra points along the minimum
      energy path (MEP) are performed at the BH&H-LYP and MP2 methods with the 6
      311G(d, p) basis set, and the energy profiles are further refined at the MC-QCISD
      level of theory. The rate constants are evaluated using canonical variational
      transition state theory (CVT) with a small-curvature tunneling correction (SCT)
      over a wide temperature range 104-2000 K. The calculated CVT/SCT rate constants
      are in good agreement with the available experimental values. Our calculations
      show that for reaction R2, the alpha-hydrogen abstraction channel and beta
      hydrogen abstraction channel are competitive over the whole temperature range.
      For reaction R3, the gamma-hydrogen abstraction channel is preferred at lower
      temperatures, while the contribution of beta-hydrogen abstraction will become
      more significant with a temperature increase. The branching ratio to the alpha
      hydrogen abstraction channel is found negligible over the whole temperature
      range.

PMID- 18710196
TI  - A linear energy relationship between activation energy and absolute hardness: a
      case study with the O(3P) atom-addition reactions to polyaromatic hydrocarbons.
AB  - A new linear relationship between absolute hardness and global activation energy
      of O-addition reaction to a series of aromatic hydrocarbons (benzene,
      naphthalene, phenanthrene, and pyrene) is presented. A total of seventeen O((3)P)
      addition reactions were evaluated. Thermal rate constants were calculated for
      each elementary reaction and used to estimate the total rate constants. This
      information was employed to obtain the global activation energy. A new linear
      relationship is shown and is estimated that it can be used within the RC-TST
      framework to predict relative rate constants for any reaction within an O
      addition to PAH class from just absolute hardness values.

PMID- 18710198
TI  - Unraveling water's entropic mysteries: a unified view of nonpolar, polar, and
      ionic hydration.
AB  - [Figure: see text]. Most chemical processes on earth are intimately linked to the
      unique properties of water, relying on the versatility with which water interacts
      with molecules of varying sizes and polarities. These interactions determine
      everything from the structure and activity of proteins and living cells to the
      geological partitioning of water, oil, and minerals in the Earth's crust. The
      role of hydrophobic hydration in the formation of biological membranes and in
      protein folding, as well as the importance of electrostatic interactions in the
      hydration of polar and ionic species, are all well known. However, the underlying
      molecular mechanisms of hydration are often not as well understood. This Account
      summarizes and extends emerging understandings of these mechanisms to reveal a
      newly unified view of hydration and explain previously mystifying observations.
      For example, rare gas atoms (e.g., Ar) and alkali-halide ions (e.g., K+ and Cl-)
      have nearly identical experimental hydration entropies, despite the significant
      charge-induced reorganization of water molecules. Here, we explain how such
      previously mysterious observations may be understood as arising from Gibbs
      inequalities, which impose rigorous energetic upper and lower bounds on both
      hydration free energies and entropies. These fundamental Gibbs bounds depend only
      on the average interaction energy of a solute with water, thus providing a deep
      link between solute-water interaction energies and entropies. One of the
      surprising consequences of the emerging picture is the understanding that the
      hydration of an ion produces two large but nearly perfectly cancelling, entropic
      contributions: a negative ion-water interaction entropy and a positive water
      reorganization entropy. Recent work has also clarified the relationship between
      the strong cohesive energy of water and the free energy required to form an empty
      hole (cavity) in water. Here, we explain how linear response theory (whose roots
      may also be traced to Gibbs inequalities) can provide remarkably accurate
      descriptions of the process of filling aqueous cavities with nonpolar, polar, or
      charged molecules. The hydration of nonpolar molecules is well-described by first
      order perturbation theory, which implies that turning on solute-water van der
      Waals interactions does not induce a significant change in water structure. The
      larger changes in water structure that are induced by polar and ionic solutes are
      well-described by second-order perturbation theory, which is equivalent to linear
      response theory. Comparisons of the free energies of nonpolar and polar or ionic
      solutes may be used to experimentally determine electrostatic contributions to
      water reorganization energies and entropies. The success of this approach implies
      that water's ability to respond to solutes of various polarities is far from
      saturated, as illustrated by simulations of acetonitrile (CH 3CN) in water, which
      reveal that even such a strongly dipolar solute only produces subtle changes in
      the structure of water.

PMID- 18710199
TI  - Dynamical resonances in the fluorine atom reaction with the hydrogen molecule.
AB  - [Reaction: see text]. The concept of transition state has played a crucial role
      in the field of chemical kinetics and reaction dynamics. Resonances in the
      transition state region are important in many chemical reactions at reaction
      energies near the thresholds. Detecting and characterizing isolated reaction
      resonances, however, have been a major challenge in both experiment and theory.
      In this Account, we review the most recent developments in the study of reaction
      resonances in the benchmark F + H 2 --> HF + H reaction. Crossed molecular beam
      scattering experiments on the F + H 2 reaction have been carried out recently
      using the high-resolution, highly sensitive H-atom Rydberg tagging technique with
      HF rovibrational states almost fully resolved. Pronounced forward scattering for
      the HF (nu' = 2) product has been observed at the collision energy of 0.52
      kcal/mol in the F + H 2 (j = 0) reaction. Quantum dynamical calculations based on
      two new potential energy surfaces, the Xu-Xie-Zhang (XXZ) surface and the Fu-Xu
      Zhang (FXZ) surface, show that the observed forward scattering of HF (nu' = 2) in
      the F + H 2 reaction is caused by two Feshbach resonances (the ground resonance
      and first excited resonance). More interestingly, the pronounced forward
      scattering of HF (nu' = 2) at 0.52 kcal/mol is enhanced considerably by the
      constructive interference between the two resonances. In order to probe the
      resonance potential more accurately, the isotope substituted F + HD --> HF + D
      reaction has been studied using the D-atom Rydberg tagging technique. A
      remarkable and fast changing dynamical picture has been mapped out in the
      collision energy range of 0.3-1.2 kcal/mol for this reaction. Quantum dynamical
      calculations based on the XXZ surface suggest that the ground resonance on this
      potential is too high in comparison with the experimental results of the F + HD
      reaction. However, quantum scattering calculations on the FXZ surface can
      reproduce nearly quantitatively the resonance picture of the F + HD reaction
      observed in the experiment. It is clear that the dynamics of the F + HD reaction
      below the threshold was dominated by the ground resonance state. Furthermore, the
      forward scattering HF (nu' = 3) channel from the F + H 2 ( j = 0) reaction was
      investigated and was attributed mainly to a slow-down mechanism over the
      centrifugal exit barrier, with small contributions from a shape resonance
      mechanism in a narrow collision energy range. A striking effect of the reagent
      rotational excitation on resonance was also observed in F + H 2 ( j = 1), in
      comparison with F + H 2 ( j = 0). From these concerted experimental and
      theoretical studies, a clear physical picture of the reaction resonances in this
      benchmark reaction has emerged, providing a textbook example of dynamical
      resonances in elementary chemical reactions.

PMID- 18710197
TI  - Tandem reactions for streamlining synthesis: enantio- and diastereoselective one
      pot generation of functionalized epoxy alcohols.
AB  - [Reaction: see text] In 1980, Sharpless and Katsuki introduced the asymmetric
      epoxidation of prochiral allylic alcohols (the Sharpless-Katsuki asymmetric
      epoxidation), which enabled the rapid synthesis of highly enantioenriched epoxy
      alcohols. This reaction was a milestone in the development of asymmetric
      catalysis because it was the first highly enantioselective oxidation reaction.
      Furthermore, it provided access to enantioenriched allylic alcohols that are now
      standard starting materials in natural product synthesis. In 1981, Sharpless and
      co-workers made another seminal contribution by describing the kinetic resolution
      (KR) of racemic allylic alcohols. This work demonstrated that small-molecule
      catalysts could compete with enzymatic catalysts in KRs. For these pioneering
      works, Sharpless was awarded the 2001 Nobel Prize with Knowles and Noyori.
      Despite these achievements, the Sharpless KR is not an efficient method to
      prepare epoxy alcohols with high enantiomeric excess (ee). First, the racemic
      allylic alcohol must be prepared and purified. KR of the racemic allylic alcohol
      must be stopped at low conversion, because the ee of the product epoxy alcohol
      decreases as the KR progresses. Thus, better methods to prepare epoxy alcohols
      containing stereogenic carbinol carbons are needed. This Account summarizes our
      efforts to develop one-pot methods for the synthesis of various epoxy alcohols
      and allylic epoxy alcohols with high enantio-, diastereo-, and chemoselectivity.
      Our laboratory developed titanium-based catalysts for use in the synthesis of
      epoxy alcohols with tertiary carbinols. The catalysts are involved in the first
      step, which is an asymmetric alkyl or allyl addition to enones. The resulting
      intermediates are then subjected to a titanium-directed diastereoselective
      epoxidation to provide tertiary epoxy alcohols. Similarly, the synthesis of
      acyclic epoxy alcohols begins with asymmetric additions to enals and subsequent
      epoxidation. The methods described here enable the synthesis of skeletally
      diverse epoxy alcohols.

PMID- 18710200
TI  - Direct determination of the ionization energies of PtC, PtO, and PtO2 with VUV
      radiation.
AB  - Photoionization efficiency curves were measured for gas-phase PtC, PtO, and PtO2
      using tunable vacuum ultraviolet (VUV) radiation at the Advanced Light Source.
      The molecules were prepared by laser ablation of a platinum tube, followed by
      reaction with CH4 or N2O and supersonic expansion. These measurements provide the
      first directly measured ionization energy for PtC, IE(PtC) = 9.45 +/- 0.05 eV.
      The direct measurement also gives greatly improved ionization energies for the
      platinum oxides, IE(PtO) = 10.0 +/- 0.1 eV and IE(PtO2) = 11.35 +/- 0.05 eV. The
      ionization energy connects the dissociation energies of the neutral and cation,
      leading to greatly improved 0 K bond dissociation energies for the neutrals:
      D0(Pt-C) = 5.95 +/- 0.07 eV, D0(Pt-O) = 4.30 +/- 0.12 eV, and D0(OPt-O) = 4.41 +/
      0.13 eV, as well as enthalpies of formation for the gas-phase molecules
      DeltaH(0)(f,0)(PtC(g)) = 701 +/- 7 kJ/mol, DeltaH(0)(f,0)(PtO(g)) = 396 +/- 12
      kJ/mol, and DeltaH(0)(f,0)(PtO2(g)) = 218 +/- 11 kJ/mol. Much of the error in
      previous Knudsen cell measurements of platinum oxide bond dissociation energies
      is due to the use of thermodynamic second law extrapolations. Third law values
      calculated using statistical mechanical thermodynamic functions are in much
      better agreement with values obtained from ionization energies and ion
      energetics. These experiments demonstrate that laser ablation production with
      direct VUV ionization measurements is a versatile tool to measure ionization
      energies and bond dissociation energies for catalytically interesting species
      such as metal oxides and carbides.

PMID- 18710201
TI  - Magnetic interactions in two heterobridged dinuclear copper(II) complexes:
      orbital complementarity or countercomplementarity?
AB  - The mechanisms of magnetic exchange interactions in two heterobridged mu-hydroxyl
      mu-X dicopper complexes A and B (X = azaindole for A and X = pyrazole for B) are
      investigated by the calculations based on density functional theory combined with
      the broken-symmetry approach (DFT-BS). It is found that although the coordination
      circumstances of the copper centers in the two complexes are very similar, the
      magnetic magnitudes and signs are diametrically opposed. By the theoretical
      analyses of magnetic orbital interaction and spin distribution, it is indicated
      that the difference between the magnetic properties of the two complexes is due
      to the distinction of orbital interaction of two bridge ligands. Namely, the weak
      ferromagnetic coupling for complex A arises from the orbital
      countercomplementarity of the hydroxo and azaindole bridges while the strong
      antiferromagnetic coupling for complex B arises from the orbital complementarity
      of the hydroxo and pyrazolato bridges.

PMID- 18710202
TI  - A combined high-resolution X-ray powder diffraction, computational, and XPS study
      of the local structure of extra-framework copper ions in over-exchanged Cu-MCM22
      zeolite.
AB  - Local structure and site distribution of extra-framework copper ions in over
      exchanged Cu-MCM22 zeolite were determined by a combination of high resolution X
      ray powder diffraction and computational analysis. X-ray diffraction data
      suggested the presence of three Cu sites in six-membered rings and one site in a
      five-membered ring close to the interlamellar region, inside the MCM-22
      supercage, whereas no Cu ions were found within the sinusoidal channels. First
      principle molecular orbital DFT calculations were employed to obtain, for the
      first time, an accurate structural description of the Cu(I) sites in the
      supercage, adding a structural and energetic interpretation to previous IR and
      EPR studies. The combined experimental and computational study suggested that
      Cu(I) sites facing 6-MRs are particularly stable. In general 5- or 4-fold
      coordination sites are located in 6-MRs while 2- or 3-fold coordination sites are
      located in 5-MRs. Three preferentially occupied sites were found in copper
      exchanged MCM-22. X-ray photoelectron spectroscopy suggested the formation of
      dispersed Cu close to the surface of MCM-22 crystallites, easily reduced to Cu(I)
      under ultrahigh vacuum conditions.

PMID- 18710203
TI  - Spectroscopy and femtosecond dynamics of excited-state proton transfer induced
      charge transfer reaction.
AB  - Fluorescence spectroscopy and femtosecond relaxation dynamics of 2-{[2-(2
      hydroxyphenyl)benzo[d]oxazol-6-yl]methylene}malononitrile (diCN-HBO) and 2-{[2-(2
      hydroxyphenyl)benzo[d]thiazol-6-yl]methylene}malononitrile (diCN-HBT) are studied
      to probe the excited-state proton transfer (ESPT) coupled charge transfer (ESCT)
      reaction. Unlike most of the ESPT/ESCT systems previously designed, in which ESCT
      takes place prior to ESPT, both diCN-HBO and diCN-HBT undergo ESPT, concomitantly
      accompanied with the charge transfer process, such that the ESPT reaction
      dynamics are directly coupled with solvent polarization effects. The long-range
      solvent polarization interactions result in a solvent-induced barrier that
      affects the overall proton transfer reaction rate. In cyclohexane, the rate
      constant of ESPT of diCN-HBO is measured to be 1.1 ps (9.1 x 10(11) s(-1)), which
      is apparently slower than that of 150 fs for the parent molecule 2-(2'
      hydroxyphenyl)benzoxazole (HBO). Upon increasing solvent polarity to, for
      example, CH 3CN, the rate of ESPT is increased to 300 fs (3.3 x 10(12) s(-1)).
      The results are rationalized by the stabilization of proton transfer tautomer,
      which possesses a large degree of charge transfer character via an increase of
      the solvent polarity, such that the corresponding solvent-induced barrier is
      reduced. We thus demonstrate a prototypical system in which the photon-induced
      nuclear motion (proton transfer) is directly coupled with solvent polarization
      and the corresponding mechanism is reminiscent of that applied in an electron
      transfer process.

PMID- 18710204
TI  - Photochemistry of protonated nitrosamine: chemical inertia of NH2NOH+ versus
      reactivity of NH3NO+.
AB  - The photochemical behavior of the protonated simplest nitrosamine [NH2NO-H](+)
      has been addressed by means of the CASPT2//CASSCF methodology in conjunction with
      the ANO-L basis sets. The relative stability of the different tautomers, namely,
      (1) NH2NOH(+), (2) NH3NO(+), and (3) NH2NHO(+), has been considered, and the
      corresponding tautomerization transition states have been characterized. With
      respect to the most chemically relevant species, it has been found that NH2NOH(+)
      corresponds to a bound structure, while NH3NO(+) corresponds to an adduct between
      NH3 and NO(+) at both CASSCF and CASPT2 levels of theory. Vertical transition
      calculations and linear interpolations on the homolytic dissociation of NH3NO(+)
      in combination with previous results on neutral nitrosamine [J. Chem. Phys. 2006,
      125, 164311] and neutral N,N-dimethylnitrosamine [J. Org. Chem. 2007, 72, 4741]
      indicate that, in acidic diluted solutions, the protonation of nitrosamine takes
      place on the excited surface. The N-N dissociation channels have been studied
      both in ground and first excited singlet state. An S1/S0 conical intersection is
      found to be responsible for the photostability of NH2NOH(+). On the contrary,
      NH3NO(+) is photochemically unstable as its first excited state is purely
      dissociative. The latter species is characterized by a twofold reactivity: the
      formation of nitrosyl cation (NO(+)) in the ground state and the photorelease of
      physiologically relevant nitric oxide radical (NO) in its first excited state.

PMID- 18710206
TI  - Energy transfer dynamics in the presence of preferential hydrogen bonding:
      collisions of highly vibrationally excited pyridine-h5, -d5, and -f5 with water.
AB  - The relaxation of highly vibrationally excited pyridine-h5, pyridine-d5, and
      pyridine-f5 (E approximately 38,000 cm(-1)) through collisions with water was
      investigated by high resolution transient IR absorption spectroscopy to
      investigate how preferential hydrogen bonding interactions impacts the energy
      transfer dynamics. Nascent rotational and translational energy gain profiles for
      scattered H2O(000) molecules with E(rot) > 1000 cm(-1) are reported. H2O(000)
      molecules scattered from pyridine-h5 and pyridine-d5 have rotational
      distributions with T(rot) = 890 K. Less rotational energy is found in H2O(000)
      scattered from pyridine-f5 for which T(rot) = 530 K. The recoil energy
      distributions are similar for the three donors with T(rel) = 400-700 K. To
      explain the results, a torque-inducing mechanism is proposed that involves
      directed movement of water between sigma and pi-hydrogen bonding interactions
      with the pyridine donors. The experimental results are consistent with this
      mechanism, and with effects due to the state-density energy dependence of the
      highly excited donor molecules. Differences in vibrational mode frequencies of
      the hot donor molecules do not appear to explain the experimental results.

PMID- 18710205
TI  - Organosulfate formation in biogenic secondary organic aerosol.
AB  - Organosulfates of isoprene, alpha-pinene, and beta-pinene have recently been
      identified in both laboratory-generated and ambient secondary organic aerosol
      (SOA). In this study, the mechanism and ubiquity of organosulfate formation in
      biogenic SOA is investigated by a comprehensive series of laboratory
      photooxidation (i.e., OH-initiated oxidation) and nighttime oxidation (i.e., NO3
      initiated oxidation under dark conditions) experiments using nine monoterpenes
      (alpha-pinene, beta-pinene, d-limonene, l-limonene, alpha-terpinene, gamma
      terpinene, terpinolene, Delta(3)-carene, and beta-phellandrene) and three
      monoterpenes (alpha-pinene, d-limonene, and l-limonene), respectively.
      Organosulfates were characterized using liquid chromatographic techniques coupled
      to electrospray ionization combined with both linear ion trap and high-resolution
      time-of-flight mass spectrometry. Organosulfates are formed only when
      monoterpenes are oxidized in the presence of acidified sulfate seed aerosol, a
      result consistent with prior work. Archived laboratory-generated isoprene SOA and
      ambient filter samples collected from the southeastern U.S. were reexamined for
      organosulfates. By comparing the tandem mass spectrometric and accurate mass
      measurements collected for both the laboratory-generated and ambient aerosol,
      previously uncharacterized ambient organic aerosol components are found to be
      organosulfates of isoprene, alpha-pinene, beta-pinene, and limonene-like
      monoterpenes (e.g., myrcene), demonstrating the ubiquity of organosulfate
      formation in ambient SOA. Several of the organosulfates of isoprene and of the
      monoterpenes characterized in this study are ambient tracer compounds for the
      occurrence of biogenic SOA formation under acidic conditions. Furthermore, the
      nighttime oxidation experiments conducted under highly acidic conditions reveal a
      viable mechanism for the formation of previously identified nitrooxy
      organosulfates found in ambient nighttime aerosol samples. We estimate that the
      organosulfate contribution to the total organic mass fraction of ambient aerosol
      collected from K-puszta, Hungary, a field site with a similar organosulfate
      composition as that found in the present study for the southeastern U.S., can be
      as high as 30%.

PMID- 18710207
TI  - Structure-activity relationship study on anti-HIV 6-desfluoroquinolones.
AB  - On the basis of our recent findings that 6-aminoquinolones inhibit the HIV Tat
      mediated transactivation, we have designed a broad series of derivatives
      identifying novel potent agents such as the 6-desfluoroquinolones 24 (HM12) and
      27 (HM13), which showed pronounced anti-HIV activity in acutely, chronically, and
      latently HIV-1 infected cell cultures. We demonstrate here that highly potent
      molecules can be obtained by optimizing the substituent in the various positions
      of the quinolone nucleus.

PMID- 18710208
TI  - Crystal structures of rat vitamin D receptor bound to adamantyl vitamin D
      analogs: structural basis for vitamin D receptor antagonism and partial agonism.
AB  - The X-ray crystal structures of the rat VDR ligand-binding domain complexed with
      19-norvitamin D compounds that contain an adamantyl substituent at the side-chain
      terminus, 2a (ADTT), 2b (ADNY), and 2c (ADMI4) and a coactivator peptide derived
      from DRIP205 are reported. These compounds show a series of partial agonistic (10
      75% efficacy)/antagonistic activities. All of these complexed receptors are
      crystallized in the canonical active conformation, regardless of their activity
      profiles. The bulky adamantyl side chain does not crowd helix 12 but protrudes
      into the gap formed by helix 11, loop 11-12, helix 3, and loop 6-7, thereby
      widening the ligand binding pocket. We suggest that these structural changes
      destabilize the active protein conformation and reduce its contribution to
      equilibrium among the active and inactive conformations. The coactivator peptide
      traps the minor active conformation, and the equilibrium shifts to the active
      conformation. As a result, these ligands show partial agonistic activities.

PMID- 18710209
TI  - Novel and potent inhibitors of 5-lipoxygenase product synthesis based on the
      structure of pirinixic acid.
AB  - A novel class of potent 5-lipoxygenase (5-LO) product synthesis inhibitors based
      on the structure of pirinixic acid (4-chloro-6-(2,3-xylidino)-2
      pyrimidinylthioacetic acid, compound 1) is presented. Systematic profiling of 1,
      i.e., esterification of the carboxylic acid, alpha-substitution, and replacement
      of the o-dimethylaniline by 6-aminoquinoline, leads to potent suppressors of 5-LO
      product formation in activated polymorphonuclear leukocytes, exemplified by ethyl
      2-[4-chloro-6-(quinoline-6-ylamino)-pyrimidin-2-ylsulfanyl]octane-1-carboxylate
      (6d, IC50 = 0.6 microM). These derivatives may possess potential for intervention
      with inflammatory and allergic diseases.

PMID- 18710210
TI  - Synthesis of novel beta-lactone inhibitors of fatty acid synthase.
AB  - Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and
      is a promising drug target for oncology. Here, we report on the syntheses and
      activity of novel inhibitors of the thioesterase domain of FAS. Using the
      structure of orlistat as a starting point, which contains a beta-lactone as the
      central pharmacophore, 28 novel congeners were synthesized and examined.
      Structural features such as the length of the alpha- and beta-alkyl chains, their
      chemical composition, and amino ester substitutions were altered and the
      resulting compounds explored for inhibitory activity toward the thioesterase
      domain of FAS. Nineteen congeners show improved potency for FAS in biochemical
      assays relative to orlistat. Three of that subset, including the natural product
      valilactone, also display an increased potency in inducing tumor cell death and
      improved solubility compared to orlistat. These findings support the idea that an
      orlistat congener can be optimized for use in a preclinical drug design and for
      clinical drug development.

PMID- 18710211
TI  - Knowledge based prediction of ligand binding modes and rational inhibitor design
      for kinase drug discovery.

PMID- 18710213
TI  - Rare-earth amidate complexes. Easily accessed initiators for epsilon-caprolactone
      ring-opening polymerization.
AB  - The direct synthesis of yttrium amidate complexes using the simple reaction of
      amide proligands and Y(N(SiMe3)2)3 results in the high-yielding preparation and
      isolation of crystalline, monomeric materials. The complex, tris(N-2',6'
      diisopropylphenyl(naphthyl)amidate)yttrium mono(tetrahydrofuran) (4), was
      structurally determined to be a 7-coordinate C1 symmetric structure, maintaining
      one bound tetrahydrofuran molecule. Compound 4 (C12H17[NCO]C10H7)3Y(C4H8O)
      crystallized in the monoclinic space group P2(1)/c with a = 13.7820(11) A, b =
      33.598(3) A, c = 16.0575(12) A, alpha = 90 degrees, beta = 98.762(3) degrees,
      gamma = 90 degrees, Z = 4. Solution phase NMR spectroscopic characterization of
      this same complex showed a highly symmetric species, consistent with a fluxional
      coordination environment for these compounds. Preliminary studies into the
      initiation of epsilon-caprolactone ring-opening polymerization using these
      complexes indicate high activity, producing high molecular weight polymer.

PMID- 18710212
TI  - Automated molecular simulation based binding affinity calculator for ligand-bound
      HIV-1 proteases.
AB  - The successful application of high throughput molecular simulations to determine
      biochemical properties would be of great importance to the biomedical community
      if such simulations could be turned around in a clinically relevant timescale. An
      important example is the determination of antiretroviral inhibitor efficacy
      against varying strains of HIV through calculation of drug-protein binding
      affinities. We describe the Binding Affinity Calculator (BAC), a tool for the
      automated calculation of HIV-1 protease-ligand binding affinities. The tool
      employs fully atomistic molecular simulations alongside the well established
      molecular mechanics Poisson-Boltzmann solvent accessible surface area (MMPBSA)
      free energy methodology to enable the calculation of the binding free energy of
      several ligand-protease complexes, including all nine FDA approved inhibitors of
      HIV-1 protease and seven of the natural substrates cleaved by the protease. This
      enables the efficacy of these inhibitors to be ranked across several mutant
      strains of the protease relative to the wildtype. BAC is a tool that utilizes the
      power provided by a computational grid to automate all of the stages required to
      compute free energies of binding: model preparation, equilibration, simulation,
      postprocessing, and data-marshaling around the generally widely distributed
      compute resources utilized. Such automation enables the molecular dynamics
      methodology to be used in a high throughput manner not achievable by manual
      methods. This paper describes the architecture and workflow management of BAC and
      the function of each of its components. Given adequate compute resources, BAC can
      yield quantitative information regarding drug resistance at the molecular level
      within 96 h. Such a timescale is of direct clinical relevance and can assist in
      decision support for the assessment of patient-specific optimal drug treatment
      and the subsequent response to therapy for any given genotype.

PMID- 18710214
TI  - Facile synthesis and functionality-dependent electrochemistry of Fe-only
      hydrogenase mimics.
AB  - A series of azadithiolate (adt)-bridged Fe-only hydrogenase model complexes,
      Fe2(CO)6(mu-adt)C6H4I-4 (1), Fe2(CO)6(mu-adt)C6H4C[triple bond]CR [R = C6H4NO2-4
      (2), C6H4CHO-4 (3), C6H4NH2-4 (4), C6H4COOH-4 (5), C6H4COOCH2CH3-4 (6), C6H4F-4
      (7), C6H5 (8), C6H4OCH3-4 (9), C6H4N(CH3)2-4 (10)], [Fe2(CO)5(PPh3)(mu-adt)C6H4I
      4 (11), and Fe2(CO)5(PPh3)(mu-adt)C6H4C[triple bond]CC6H4NO2-4 (12), have been
      synthesized in high yields under mild conditions. The linear geometry and
      rigidity of a triple bond act as an effective bridge to anchor a functionality
      ranging from electron-donating to electron-accepting, even coordinative groups in
      the adt model complexes. X-ray crystal analysis of 2, 3, and 6-12 reveals that
      the model complexes retain the butterfly structure of Fe2S2 model analogues. A
      rigid phenylacetylene offers excellent control over the distance between the
      functional group and the active site of Fe2S2 model complexes. The unusual Fe-Fe
      distance and the angles found in the molecular packing of 6 are originated from
      the intriguing intermolecular C-H...O and C-H...S interactions. More importantly,
      electrochemical studies reveal that all of the complexes can catalyze
      electrochemical reduction of protons to molecular hydrogen, but the reduction
      potential for the electron-transfer step can be remarkably altered by the
      functionality R. The electroreductively active nitro group in 2 and 12 displays
      the enhanced current at a potential substantially less negative than the
      reduction of [Fe(I)Fe(I)] + e(-) --> [Fe(I)Fe(0)], which is most accessible and
      becomes the initial step. For complex 3, the second reduction peak for the
      electron-transfer step involves the contribution from the aldehyde functionality.
      As the electroreductively inactive groups are incorporated, the reduction process
      of [Fe(I)Fe(I)] + e(-) --> [Fe(I)Fe(0)] appears first and the second reduction
      peak for the electron-transfer step from the [Fe(I)Fe(0)] + e(-) --> [Fe(0)Fe(0)]
      process for 4-10 is clearly observed. Therefore, the order of electron and proton
      uptake is closely related to the electroreductively active functionality, R.
      Varying the nature of the functionality R leads to the electron-transfer step
      changes from the reduction of the electroreductively active R group to the active
      site of Fe2S2 model complexes subsequently. Accordingly, notwithstanding, acetic
      acid is too weak to protonate the series of 2-12, different reduction pathways
      can be followed, and the electrochemically catalyzed behavior may occur at
      different reduction levels.

PMID- 18710215
TI  - Expedient multi-step synthesis of organometallic complexes of Tc and Re in high
      effective specific activity. A new platform for the production of molecular
      imaging and therapy agents.
AB  - For over thirty years, instant labeling kits which involve no purification steps
      have been the only method used to prepare (99m)Tc radiopharmaceuticals for
      clinical studies. To address the limitations imposed by instant kits, which is
      hindering the development of molecularly targeted Tc- and Re-based imaging and
      therapy agents, a new strategy for the rapid multistep synthesis and purification
      of organometallic technetium-based molecular probes and corresponding rhenium
      based therapeutic analogues was developed. Beginning with MO4(-) (M = (99m)Tc,
      (186/188)Re), the carbonyl precursor [M(CO)3(H2O)3](+) was synthesized in 3 min
      in quantitative yield in a microwave reactor. A dipicolyl ligand was added and
      the chelate complex was formed in high yield in 2 min using microwave heating at
      150 degrees C. This was followed by a new purification strategy to remove
      unlabeled ligand which entailed using a copper resin/C18 solid phase extraction
      protocol giving the desired product in greater than 78% decay corrected yield
      (dcy). Conversion to the corresponding succinimidyl active ester was achieved
      following a 5 min microwave irradiation at 120 degrees C and C18 solid phase
      extraction purification in 60% dcy. A series of amides were prepared subsequently
      by microwave heating at 120 degrees C for 5 min producing the desired targets in
      greater than 86% dcy. The reported method represents a move away from traditional
      instant kits toward more versatile platform synthesis and purification
      technologies that are better suited for producing modern molecular imaging and
      therapy agents.

PMID- 18710216
TI  - Functionalization of aminophosphanes: synthesis and X-ray crystal structure of
      novel dilithium and trilithium complexes containing silicon-fused heteronuclear
      SiN2PLi five-membered rings.
AB  - A first structurally characterized primary aminophosphane (Ar 2PNH 2 ( 2); Ar =
      2,4,6- iPr 3C 6H 2) that is a stable solid at room temperature without
      decomposition by self-condensation is reported. Reactions of N-phosphanyllithium
      amide ( tBu 2PNHLi ( 3)) with Me 2SiCl 2 and MeSiCl 3 in Et 2O result in the
      formation of Me 2Si(NHP tBu 2) 2 ( 4) and MeSi(NHP tBu 2) 3 ( 5), respectively.
      Subsequent treatment of 4 and 5 with 2 and 3 equiv of nBuLi gave the dilithium (
      6) and trilithium ( 7) complexes, respectively. Further treatment of 5 with 3
      equiv of AlMe 3 yielded the trialuminum complex MeSi[N(AlMe 2)P tBu 2] 3 ( 8).
      These three complexes were investigated by microanalysis and multinuclear NMR
      spectroscopy. The dilithium complex [Me 2Si(NLiP tBu 2) 2.3THF] ( 6) and the
      trilithium complex [MeSi(NLiP tBu 2) 3.3Et 2O] ( 7) were further characterized by
      single-crystal X-ray structural analysis.

PMID- 18710217
TI  - Hydrolytic metal with a hydrophobic periphery: titanium(IV) complexes of
      naphthalene-2,3-diolate and interactions with serum albumin.
AB  - Serum albumin, the most abundant protein in human plasma (700 microM), binds
      diverse ligands at multiple sites. While studies have shown that serum albumin
      binds hard metals in chelate form, few have explored the trafficking of these
      metals by this protein. Recent work demonstrated that serum albumin may play a
      pivotal role in the transport and bioactivity of titanium(IV) complexes,
      including the anticancer drug candidate titanocene dichloride. The current work
      explores this interaction further by using a stable Ti(IV) complex that presents
      a hydrophobic surface to the protein. Ti(IV) chelation by 2,3
      dihydroxynaphthalene (H2L1) and 2,3-dihydroxynaphthalene-6-sulfonate (H2L2)
      affords water soluble complexes that protect Ti(IV) from hydrolysis at pH 7.4 and
      bind to bovine serum albumin (BSA). The solution and solid Ti(IV) coordination
      chemistry were explored by aqueous spectropotentiometric titrations and X-ray
      crystallography, respectively, and with complementary electrochemistry, mass
      spectrometry, and IR and NMR spectroscopies. Four Ti(IV) species of L2, TiLH0,
      TiL2H0, TiL3H0, and TiL3H(-1), adequately represent the pH-dependent speciation.
      The isolation of Ti(C10H6O2)2 x 1.75 H2O at pH approximately 3 and
      K2[Ti(C10H6O2)3] x 3 H2O and Cs5[Ti(C10H5O5S)3] x 2.5 H2O at pH approximately 7
      correlates well with the solution studies. At pH 7.4 and micromolar
      concentrations, the TiL3H0 species are favored. The Ti(naphthalene-2,3
      diolate)3(2-) complex binds with moderate affinity to multiple sites of BSA. The
      primary site (K = 2.05 +/- 0.34 x 10(6) M(-1)) appears to be hydrophobic as
      indicated by competition studies with different ligands and a hydrophilic Ti(IV)
      complex. The Ti(naphthalene-2,3-diolate)3(2-) interaction with the Fe(III)
      binding protein human serum transferrin (HsTf), a protein also important for
      Ti(IV) transport, and DNA was examined. The complex does not deliver Ti(IV) to
      HsTf and while it does bind to DNA, no cleavage promotion activity is observed.
      This investigation provides insight into the use of ligands to direct metal
      binding at different sites of albumin, which may facilitate transport to distinct
      targets.

PMID- 18710218
TI  - Synthesis, structure, and high-temperature thermoelectric properties of boron
      doped Ba8Al14Si31 clathrate I phases.
AB  - Single crystals of boron-doped Ba8Al14Si31 clathrate I phase were prepared using
      Al flux growth. The structure and elemental composition of the samples were
      characterized by single-crystal and powder X-ray diffraction; elemental analysis;
      and multinuclear (27)Al, (11)B, and (29)Si solid-state NMR. The samples'
      compositions of Ba8B0.17Al14Si31, Ba8B0.19Al15Si31, and Ba8B0.32Al14Si31 were
      consistent with the framework-deficient clathrate I structure Ba8Al(x)Si(42
      3/4x)cube(4-1/4x) (x = 14, cube = lattice defect). Solid-state NMR provides
      further evidence for boron doped into the framework structure. Temperature
      dependent resistivity indicates metallic behavior, and the negative Seebeck
      coefficient indicates that transport processes are dominated by electrons.
      Thermal conductivity is low, but not significantly lower than that observed in
      the undoped Ba8Al14Si31 prepared in the same manner.

PMID- 18710219
TI  - N2-functionalized blue luminescent guanosines by 2,2'-dipyridylamino and 2-(2'
      pyridyl)benzimidazolyl chelate groups and their interactions with Zn(II) ions.
AB  - The syntheses of new blue luminescent N(2)-modified guanosine derivatives with
      chromophores p-4,4'-biphenyl-NPh2 (1a), p-4,4'-biphenyl-N(2-py)2 (1b), and p-4,4'
      biphenyl-2-(2'-pyridyl)benzimidazolyl (1c), respectively, have been achieved.
      These new N(2)-guanosines are moderate blue emitters with lambda(max) = 395 nm
      (1a), 370 nm (1b), and 403 nm (1c) and Phi = 0.13, 0.07, and 0.10 in
      tetrahydrofuran, respectively. Spectroscopic studies and density-functional
      theory calculations established that the guanine moiety and the new chromophore
      in all three molecules are involved in the luminescent process. We have also
      established that guanosines 1a-1c can interact with metal ions such as Zn(II).
      The interactions of Zn(II) ions with the three guanosines were examined via
      absorption, fluorescence, circular dichroism (CD), and NMR spectroscopic
      analyses. We have found that these guanosines display a distinct fluorescent
      response toward Zn(II) ions which can be attributed to the presence of the
      chelate chromophore N(2-py)2 in 1b and 2-py-benzimidazolyl in 1c. For 1a and 1b,
      the addition of Zn(II) ions causes straight fluorescent quenching while for 1c
      the addition of Zn(II) ions causes quenching initially, which is followed by a
      distinct spectral red shift and the intensity enhancement of the new emission
      peak. NMR and CD studies demonstrated that the Zn(II) ions bind preferentially to
      the guanine moiety in 1a and 1b but to the 2-(2'-py)benzimidazolyl chelate site
      in 1c. Moreover, the anion-dependent CD response of 1a-1c toward Zn(II) salts
      points to the possible involvement of intramolecular hydrogen bonding between the
      acetate bound to the Zn(II) ion and the hydroxyl groups of the guanosine.

PMID- 18710220
TI  - Hydrothermal synthesis of vanadium oxyfluoride chains incorporating covalently
      bound copper coordination complexes.
AB  - An exploration of the hydrothermal synthesis of vanadium oxyfluorides in the
      presence of copper-amine coordination complexes has produced six new compounds
      exhibiting novel one-dimensional structural features. [C 2H 8N][Cu(C 5H 5N) 4][V
      2O 2F 7] incorporates dimeric vanadium(IV) oxyfluoride units (in this case, face
      sharing V-centered octahedra) into a compound of this type for the first time;
      this composition has been prepared in two polymorphs, 1 and 2, which differ in
      chain configuration and orientation, mediated by H bonding of the uncoordinated
      dimethylammonium cation. A differing dimeric vanadium(IV) oxyfluoride anion
      (based on edge-sharing V-centered octahedra) occurs in [C 3H 5N 2] 2[Cu(C 3H 4N
      2) 4][V 2O 2F 8], 4, which incorporates imidazole in two structural roles: as
      both a ligand and template. [Cu 2F 2(C 10H 10N 3) 2][V 2O 7], 5, and [Cu(C 5H 5N)
      2(C 2H 8N 2)][(VO 3) 2], 6, both contain V (5+) in tetrahedral coordination, in
      dimers in the former and infinite chains in the latter. In the case of 6, the
      copper moieties act as "decoration" rather than as linkers to the vanadium oxide
      sublattice.

PMID- 18710221
TI  - Ferroelectric heterobimetallic clusters with ferromagnetic interactions.
AB  - Two homochiral trinuclear clusters, {(MeTp)2Fe2(CN)6Ni[(1R,2R)-chxn]2} (1) and
      {(MeTp)2Fe2(CN)6Ni[(1S,2S)-chxn]2} (2) [chxn = 1,2-diaminocyclohexane; MeTp =
      methyltris(pyrazolyl)borate], have been synthesized and structurally
      characterized. Ferroelectric and magnetic measurements reveal that they are rare
      examples of metal-organic compounds bearing ferroelectricity and intramolecular
      ferromagnetic interactions.

PMID- 18710222
TI  - Spherical versus linear anion encapsulation in the cavity of a protonated
      azacryptand.
AB  - Grams scale synthesis of an octaaminocryptand L(2) with high yield is obtained in
      one-pot by low-temperature [2 + 3] condensation of tris(2-aminoethyl)amine with
      isophthalaldehyde, followed by sodium borohydride reduction. Structural aspects
      of octaaminocryptand L(2) x MeOH, binding of iodide (spherical) and bichloride
      (linear) in L(2), (1,4,11,14,17,24,29,36-octa-azapentacyclo
      [12.12.12..2(6,9).2(19,22).2(31,34)]-tetratetraconta
      6(43),7,9(44),19(41),20,22(42),31(39),32,34(40)-nonane, N(CH2CH2NHCH2-m-xylyl
      CH2NHCH2CH2)3N), in the hexaprotonated and tetraprotonated states, respectively,
      are examined. Crystallographic results show binding of single iodide
      [H6L(2)I](I)5 x 4 H2O, (2), in a hexaprotonated cryptand L(2). Monotopic
      recognition of iodide is observed via (N-H)(+)...iodide interactions. The
      tetraprotonation of L(2) by hydrochloric acid showed the formation and
      encapsulation of a bichloride inside the cavity, which is examined from the
      single-crystal X-ray study. Encapsulation and binding of a proton-bridged linear
      bichloride inside the cavity of tetraprotonated L(2), [H4L(2)(ClHCl)](Cl)3 x nH2O
      (3), via (N-H)(+)...chloride interactions is observed in the structural
      investigation. This study shows that degree of protonation and its distribution
      in the receptor architecture play an important role in guest encapsulation.
      Further, it represents the first example of an encapsulated bichloride inside the
      cavity of an organic host.

PMID- 18710223
TI  - Harnessing scorpionate ligand equilibria for modeling reduced nickel superoxide
      dismutase intermediates.
AB  - Hydrotris(3-phenyl-5-methylpyrazoyl)boratonickel(II) complexes with
      organoxanthate or dithiocarbamate coligands equilibrate between kappa(2)- and
      kappa(3)-chelation modes of the scorpionate ligand in solution, connecting N2S2
      square-planar and N3S2 pyramidal ligand fields and a spin crossover. The
      complexes also exhibit quasi-reversible oxidations at low anodic potentials, thus
      modeling the structure, dynamics, and redox reactivity of the reduced NiSOD
      active site.

PMID- 18710225
TI  - Nanoparticle-mediated intervalence transfer.
AB  - Nanoparticle-mediated intervalence transfer was reported with ferrocene moieties
      that were attached onto the ruthenium nanoparticle surface by ruthenium-carbene
      pi bonds. The resulting particles exhibited two pairs of voltammetric waves with
      a potential spacing of about 200 mV and a rather intense absorption peak in the
      near-infrared range (approximately 1930 nm) at mixed valence. Both features
      suggested Class II characteristics of the intraparticle intervalence transfer
      that mainly arose from through-bond interactions between the metal centers.
      Quantum calculations based on density functional theory showed that the
      nanoparticle core electrons served as conducting band states for the effective
      charge delocalization between particle-bound ferrocene moieties.

PMID- 18710224
TI  - Most efficient cocaine hydrolase designed by virtual screening of transition
      states.
AB  - Cocaine is recognized as the most reinforcing of all drugs of abuse. There is no
      anticocaine medication available. The disastrous medical and social consequences
      of cocaine addiction have made the development of an anticocaine medication a
      high priority. It has been recognized that an ideal anticocaine medication is one
      that accelerates cocaine metabolism producing biologically inactive metabolites
      via a route similar to the primary cocaine-metabolizing pathway, i.e., cocaine
      hydrolysis catalyzed by plasma enzyme butyrylcholinesterase (BChE). However, wild
      type BChE has a low catalytic efficiency against the abused cocaine. Design of a
      high-activity enzyme mutant is extremely challenging, particularly when the
      chemical reaction process is rate-determining for the enzymatic reaction. Here we
      report the design and discovery of a high-activity mutant of human BChE by using
      a novel, systematic computational design approach based on transition-state
      simulations and activation energy calculations. The novel computational design
      approach has led to discovery of the most efficient cocaine hydrolase, i.e., a
      human BChE mutant with an approximately 2000-fold improved catalytic efficiency,
      promising for therapeutic treatment of cocaine overdose and addiction as an
      exogenous enzyme in human. The encouraging discovery resulted from the
      computational design not only provides a promising anticocaine medication but
      also demonstrates that the novel, generally applicable computational design
      approach is promising for rational enzyme redesign and drug discovery.

PMID- 18710226
TI  - Using alpha-helical coiled-coils to design nanostructured metalloporphyrin
      arrays.
AB  - We have developed a computational design strategy based on the alpha-helical
      coiled-coil to generate modular peptide motifs capable of assembling into
      metalloporphyrin arrays of varying lengths. The current study highlights the
      extension of a two-metalloporphyrin array to a four-metalloporphyrin array
      through the incorporation of a coiled-coil repeat unit. Molecular dynamics
      simulations demonstrate that the initial design evolves rapidly to a stable
      structure with a small rmsd compared to the original model. Biophysical
      characterization reveals elongated proteins of the desired length, correct
      cofactor stoichiometry, and cofactor specificity. The successful extension of the
      two-porphyrin array demonstrates how this methodology serves as a foundation to
      create linear assemblies of organized electrically and optically responsive
      cofactors.

PMID- 18710227
TI  - Oriented organic islands and one-dimensional chains on a Au(111) surface
      fabricated by electrodeposition: an STM study.
AB  - Organic islands and oriented one-dimensional (1D) chains are fabricated on a
      Au(111) surface by electrodeposition. The cyclic voltammograms (CVs) of Au(111)
      in solutions containing nitrobenzene and picric acid show an electrochemical
      reaction in a negative potential region, which results in irreversible reductive
      deposition. The deposition process is monitored by in situ electrochemical
      scanning tunneling microscopy (ECSTM). At the double layer potential region, for
      example, nitrobenzene molecules form a well-defined adlayer in a (square root(3)
      x square root(3)) structure. With potential shifting negative to the reductive
      region, nitrobenzene is reduced to hydroxyaminobenzene. Organic islands were
      formed first and then aggregated into ordered 1D chains. The formation of these
      organic islands and 1D chains is completely potential-dependent. Intriguingly,
      the so-prepared islands and 1D chains are well-oriented along the reconstructed
      lines of the underlying Au(111) substrate and stable under ambient conditions
      even if the sample was removed from electrolyte solution. The results reported
      here provide a simple and effective method to fabricate oriented organic nanodots
      and nanowires on a solid surface by an electrochemical technique.

PMID- 18710228
TI  - Hydroxylase activity of Met471Cys tyramine beta-monooxygenase.
AB  - A series of mutations was targeted at the methionine residue, Met471,
      coordinating the Cu(M) site of tyramine beta-monooxygenase (TbetaM). The
      methionine ligand at Cu(M) is believed to be key to dioxygen activation and the
      hydroxylation chemistry of the copper monooxygenases. The reactivity and copper
      binding properties of three TbetaM mutants, Met471Asp, Met471Cys, and Met471His,
      were examined. All three mutants show similar metal binding affinities to wild
      type TbetaM in the oxidized enzyme forms. EPR spectroscopy suggests that the
      Cu(II) coordination geometry is identical to that of the WT enzyme. However,
      substrate hydroxylation was observed for the reaction of tyramine solely with
      Met471Cys TbetaM. Met471Cys TbetaM provides the first example of an active mutant
      directed at the Cu(M) site of this class of hydroxylases. The reactivity and
      altered kinetics of the Met471Cys mutant further highlight the central role of
      the methionine residue in the enzyme mechanism. The sole ability of the cysteine
      residue to support activity among the series of alternate amino acids
      investigated is relevant to theoretical and biomimetic investigations of dioxygen
      activation at mononuclear copper centers.

PMID- 18710229
TI  - "Three-dimensional hybridization" with polyvalent DNA-gold nanoparticle
      conjugates.
AB  - We have determined the minimum number of base pairings necessary to stabilize DNA
      Au NP aggregates as a function of salt concentration for particles between 15 and
      150 nm in diameter. Significantly, we find that sequences containing a single
      base pair interaction are capable of effecting hybridization between 150 nm DNA
      Au NPs. While traditional DNA hybridization involves two strands interacting in
      one dimension (1D, Z), we propose that hybridization in the context of an
      aggregate of polyvalent DNA-Au NP conjugates occurs in three dimensions (many
      oligonucleotides oriented perpendicular to the X, Y plane engage in base
      pairing), making nanoparticle assembly possible with three or fewer base pairings
      per DNA strand. These studies enabled us to compare the stability of duplex DNA
      free in solution and bound to the nanoparticle surface. We estimate that 4-8, 6
      19, or 8-33 additional DNA bases must be added to free duplex DNA to achieve
      melting temperatures equivalent to hybridized systems formed from 15, 60, or 150
      nm DNA-Au NPs, respectively. In addition, we estimate that the equilibrium
      binding constant (K(eq)) for 15 nm DNA-Au NPs (3 base pairs) is approximately 3
      orders of magnitude higher than the K(eq) for the corresponding nanoparticle free
      system.

PMID- 18710230
TI  - Ligand controlled highly regio- and enantioselective synthesis of alpha
      acyloxyketones by palladium-catalyzed allylic alkylation of 1,2-enediol
      carbonates.
AB  - The palladium catalyzed decarboxylative asymmetric allylic alkylation of allyl
      1,2-enediol carbonates 1 can decompose to either alpha-hydroxyketones 3 or alpha
      hydroxyaldehydes 4. The product distribution is largely controlled by the ligand.
      Using Lnaph in DME we exclusively obtained the ketone product in good to
      excellent yields and high enantiomeric excesses. The reaction proceeds under
      extremely mild conditions, so we can have a broad range of choices of OR. Besides
      the commonly used protection groups such as OAc and OPiv, a more functionalized
      group such as methyl but-2-enoyl group can also be used, downstream process of
      which can afford other synthetically interesting structures.

PMID- 18710231
TI  - A role for confined water in chaperonin function.
AB  - Chaperonins engulf other proteins and accelerate their folding by an unknown
      mechanism. Here, we combine all-atom molecular dynamics simulations with data
      from experimental assays of the activity of the bacterial chaperonin GroEL to
      demonstrate that a chaperonin's ability to facilitate folding is correlated with
      the affinity of its interior surface for water. Our results suggest a novel view
      of the behavior of confined water for models of in vivo protein folding
      scenarios.

PMID- 18710232
TI  - Chain-length dependent nematic ordering of conjugated polymers in a liquid
      crystal solvent.
AB  - In this communication we demonstrate the dependence of the solute order parameter
      on the solute molecular weight for polymer solutes dissolved in liquid
      crystalline solvents. Using ensemble absorption polarization spectroscopy
      together with single molecule fluorescence polarization measurements, we have
      determined the order parameter of the conjugated polymer MEH-PPV (poly[2-methoxy
      5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene]) in the liquid crystal 5CB (4-cyano
      4-n-pentylbiphenyl) as a function of polymer chain length. Ensemble absorption
      polarization measurements agree well with results obtained by single molecule
      fluorescence polarization spectroscopy, indicating a large-scale ordering of the
      MEH-PPV solute in 5CB. These results demonstrate that the increasing number of
      defects for larger polymer weights inherently limits the alignment of the polymer
      solute.

PMID- 18710233
TI  - A latent oxazoline electrophile for N-O-C bond formation in pseudomonine
      biosynthesis.
AB  - Nitrogen-heteroatom bonds figure prominently in the structural, chemical, and
      functional diversity of natural products. In the case of Pseudomonas siderophore
      pseudomonine, an N-O hydroxamate linkage is found uncommonly configured in an
      isoxazolidinone ring. In an effort to understand the biogenesis of this
      heterocycle, we have characterized the pseudomonine synthetase in vitro and
      reconstituted the complete biosynthetic pathway. Our results indicate that the
      isoxazolidinone of pseudomonine arises from spontaneous rearrangement of an
      oxazoline precursor. To the best of our knowledge, this is a previously
      uncharacterized mode of post-assembly line heterocyclization. Our results
      establish the oxygen of the ubiquitous siderophore hydroxamate functionality as a
      nucleophile and may be indicative of general strategy for N-O-C bond formation in
      nature.

PMID- 18710234
TI  - Mechanistic study of asymmetric oxidative biaryl coupling: evidence for self
      processing of the copper catalyst to achieve control of oxidase vs oxygenase
      activity.
AB  - Copper(I) and copper(II) 1,5-diaza-cis-decalin complexes [(N2)Cu] are effective
      precatalysts for aerobic oxidative coupling of naphthol substrates. Mechanistic
      studies, however, reveal that these complexes are not the reactive form of the
      catalyst under steady-state conditions. Rather, the active catalyst forms in a
      presteady-state self-processing step that involves oxygenation of the naphthol
      substrate. The oxygenated substrate, NapHOX, serves as a cofactor that combines
      with the (N2)Cu complexes to achieve highly selective, steady-state oxidase
      reactivity (aerobic oxidative biaryl coupling).

PMID- 18710235
TI  - Epoxide hydrolase Lsd19 for polyether formation in the biosynthesis of lasalocid
      A: direct experimental evidence on polyene-polyepoxide hypothesis in polyether
      biosynthesis.
AB  - Polyether metabolites are an important class of natural products. Although their
      biosynthesis, especially construction of polyether skeletons, attracted organic
      chemists for many years, no experimental data on the enzymatic polyether
      formation has been obtained. In this study, a putative epoxide hydrolase gene
      lsd19 found on the biosynthetic gene cluster of an ionophore polyether lasalocid
      was cloned and successfully overexpressed in Escherichia coli. Using the purified
      Lsd19, a proposed substrate, bisepoxyprelasalocid, and its synthesized analogue
      were successfully converted into lasalocid A and its derivative via a 6-endo-tet
      cyclization mode. On the other hand, treatment of the bisepoxide with
      trichloroacetic acid gave isolasalocid A via a 5-exo-tet cyclization mode.
      Therefore, the enzymatic conversion observed in this study unambiguously showed
      that the bisepoxyprelasalocid is an intermediate of the lasalocid biosynthesis
      and that Lsd19 catalyzes the sequential cyclic ether formations involving an
      energetically disfavored 6-endo-tet cyclization. This is the first example of the
      enzymatic epoxide-opening reactions leading to a polyether natural product.

PMID- 18710236
TI  - Strong correlation between SHAPE chemistry and the generalized NMR order
      parameter (S2) in RNA.
AB  - The functions of most RNA molecules are critically dependent on the distinct
      local dynamics that characterize secondary structure and tertiary interactions
      and on structural changes that occur upon binding by proteins and small molecule
      ligands. Measurements of RNA dynamics at nucleotide resolution set the foundation
      for understanding the roles of individual residues in folding, catalysis, and
      ligand recognition. In favorable cases, local order in small RNAs can be
      quantitatively analyzed by NMR in terms of a generalized order parameter, S2.
      Alternatively, SHAPE (selective 2'-hydroxyl acylation analyzed by primer
      extension) chemistry measures local nucleotide flexibility in RNAs of any size
      using structure-sensitive reagents that acylate the 2'-hydroxyl position. In this
      work, we compare per-residue RNA dynamics, analyzed by both S2 and SHAPE, for
      three RNAs: the HIV-1 TAR element, the U1A protein binding site, and the
      Tetrahymena telomerase stem loop 4. We find a very strong correlation between the
      two measurements: nucleotides with high SHAPE reactivities consistently have low
      S2 values. We conclude that SHAPE chemistry quantitatively reports local
      nucleotide dynamics and can be used with confidence to analyze dynamics in large
      RNAs, RNA-protein complexes, and RNAs in vivo.

PMID- 18710237
TI  - Site-specific radical directed dissociation of peptides at phosphorylated
      residues.
AB  - Site-specific fragmentation of peptides at phosphorylated serine or threonine
      residues is demonstrated. This radical directed cleavage is accomplished by a two
      step procedure. First the phosphate is replaced with naphthalenethiol using well
      established Michael Addition chemistry. Second, the modified peptide is
      electrosprayed and subjected to irradiation at 266 nm. Absorption at naphthalene
      causes homolytic cleavage of the connecting carbon-sulfur bond yielding a radical
      in the beta-position. Subsequent rearrangement cleaves the peptide backbone
      yielding a d-type fragment. This chemistry is generally applicable as
      demonstrated by experiments with several different peptides. Assignment of
      phosphorylation sites is greatly facilitated by this approach, particularly for
      peptides containing multiple serine or threonine residues.

PMID- 18710239
TI  - Automated NMR assignment of protein side chain resonances using automated
      projection spectroscopy (APSY).
AB  - This paper describes an automated method for sequence-specific NMR assignment of
      the aliphatic resonances of protein side chains in small- and medium-sized
      globular proteins in aqueous solution. The method requires the recording of a
      five-dimensional (5D) automated projection spectroscopy (APSY-) NMR experiment
      and the subsequent analysis of the APSY peak list with the algorithm ALASCA
      (Algorithm for local and linear assignment of side chains from APSY data). The 5D
      APSY-HC(CC-TOCSY)CONH experiment yields 5D chemical shift correlations of
      aliphatic side chain C-H moieties with the backbone atoms H(N), N, and C'. A
      simultaneous variation of the TOCSY mixing times and the projection angles in
      this APSY-type TOCSY experiment gives access to all aliphatic C-H moieties in the
      20 proteinogenic amino acids. The correlation peak list resulting from the 5D
      APSY-HC(CC-TOCSY)CONH experiment together with the backbone assignment of the
      protein under study is the sole input for the algorithm ALASCA that assigns
      carbon and proton resonances of protein side chains. The algorithm is described,
      and it is shown that the aliphatic parts of 17 of the 20 common amino acid side
      chains are assigned unambiguously, whereas the remaining three amino acids are
      assigned with a certainty of above 95%. The overall feasibility of the approach
      is demonstrated with the globular 116-residue protein TM1290, for which reference
      assignments are known. For this protein, 97% of the expected side chain carbon
      atoms and 87% of the expected side chain protons were detected with the 5D APSY
      HC(CC-TOCSY)CONH experiment in 24 h of spectrometer time, and all these
      resonances were correctly assigned by ALASCA. Based on the experience with
      TM1290, we expect that the approach presented in this work is routinely
      applicable to globular proteins with sizes up to at least 120 amino acids.

PMID- 18710238
TI  - 13C-labeled N-acetyl-neuraminic acid in aqueous solution: detection and
      quantification of acyclic keto, keto hydrate, and enol forms by 13C NMR
      spectroscopy.
AB  - Aqueous solutions of N-acetyl-neuraminic acid (Neu5Ac, 1) labeled with (13)C at
      C1, C2, and/or C3 were analyzed by (13)C NMR spectroscopy to detect and quantify
      the acyclic forms (keto, keto hydrate, enol) present at varying pHs. In addition
      to pyranoses, solutions contained the keto form, based on the detection of C2
      signals at approximately 198 ppm (approximately 0.7% at pH 2). Spectra of [2
      (13)C] and [3-(13)C] isotopomers contained signals arising from labeled carbons
      at approximately 143 and approximately 120 ppm, respectively, which were
      attributed to enol forms. Solution studies of [1,2,3-(13)C3] 1 substantiated the
      presence of enol (approximately 0.5% at pH 2). Enol was not detected at pH > 6.0.
      A C2 signal observed at approximately 94 ppm was identified as C2 of the keto
      hydrate (approximately 1.9% at pH 2), based partly on its abundance as a function
      of solution pH. Density functional theory (DFT) calculations were used to study
      the effect of enol and hydrate structure on J(CH) and J(CC) values involving C2
      and C3 of these forms. Solvated DFT calculations showed that (2)J(C2,H3) in cis
      and trans enols have similar magnitudes but opposite signs, making this J
      coupling potentially useful to distinguish enol configurations. Solvent deuterium
      exchange studies of 1 showed rapid incorporation of (2)H from (2)H2O at H3 axial
      in the pyranoses at p(2)H 8.0, followed by slower exchange at H3 equatorial. The
      acyclic keto form, which presumably participates in this reaction, must assume a
      pseudo-cyclic conformation in solution in order to account for the exchange
      selectivity. Weak (13)C signals arising from labeled species were also observed
      consistently and reproducibly in aqueous solutions of (13)C-labeled 1, possibly
      arising from products of lactonization or intermolecular esterification.

PMID- 18710240
TI  - Rhodium-catalyzed asymmetric ring-opening alkynylation of azabenzonorbornadienes.
AB  - Asymmetric ring-opening alkynylation of meso-azabenzonorbornadienes with
      (triisopropylsilyl)acetylene giving 2-alkynyl-1-aminodihydronaphthalenes took
      place in high yields with high enantioselectivity in the presence of a
      rhodium/(R)-DTBM-segphos catalyst.

PMID- 18710241
TI  - Practical Heck-Mizoroki coupling protocol for challenging substrates mediated by
      an N-heterocyclic carbene-ligated palladacycle.
AB  - A highly active, N-heterocyclic carbene-palladacycle precatalyst for the Heck
      Mizoroki reaction was rationally designed. The complex can be synthesized on a
      large scale in excellent yield by a novel, one-pot, three-component reaction and
      is tolerant to air, moisture, and long-term storage. A wide range of challenging
      substrates is successfully coupled under a simple and user-friendly reaction
      protocol.

PMID- 18710242
TI  - Determination of florfenicol amine residues in animal edible tissues by an
      indirect competitive ELISA.
AB  - Florfenicol (FF) is a broad-spectrum antibiotic used increasingly in aquaculture,
      livestock, and poultry to treat diseases. To avoid using labor-intensive
      instrumental methods to detect residues of FF in food and food products, a simple
      and convenient indirect competitive enzyme-linked immunosorbent assay (ic-ELISA)
      method for florfenicol's major metabolite, florfenicol amine (FFA), was developed
      using a polyclonal antibody prepared in this study. FFA was covalently attached
      to carrier protein as immunogen by using the glutaraldehyde method. The
      antibodies obtained were characterized by an ELISA method and showed excellent
      specificity and sensitivity with the 50% inhibition values (IC 50) of 3.34
      microg/L for FFA in PBS buffer. In the ELISA, sample extractions were performed
      by ethyl acetate/ammonium hydroxide (90 + 10, v/v) following combined acid
      hydrolysis of FF and its known metabolites. The limits of detection (LOD)
      calculated from the analysis of 20 known negative swine muscle, chicken muscle,
      and fish samples were 3.08, 3.3, and 3.86 microg/kg (mean + 3 SD), respectively.
      Recoveries of FFA fortified at the levels of 5, 50, 100, and 300 microg/kg ranged
      from 64.6 to 124.7%, with coefficients of variation of 11.3-25.8% over the range
      of FFA concentrations studied. Validation of the ELISA method with FFA-fortified
      swine muscle at the levels of 10, 50, 100, and 200 microg/kg was carried out
      using GC, resulting in a similar correlation in swine muscle ( r = 0.97). The
      results suggest that this ELISA is a specific, accurate, and sensitive method,
      which is suitable for use as a screening method to detect residues of FFA in
      animal edible tissues.

PMID- 18710243
TI  - Impact of alkalization on the antioxidant and flavanol content of commercial
      cocoa powders.
AB  - Cocoa is a food ingredient that is important for the contribution of flavor to
      foods but is also associated with potential health benefits. The chemistry
      thought to be responsible for its cardiovascular health benefits is the flavanol
      (flavan-3-ol) antioxidants. Evidence from the literature indicates that natural
      cocoas are high in flavanols, but when the cocoa is processed with alkali, also
      known as Dutch processing or Dutching, the flavanols are substantially reduced.
      This paper provides a survey of the physical and chemical composition of
      representative natural cocoas and lightly, medium, and heavily alkalized cocoas.
      As part of the survey, both brown/black and red/brown alkali-processed cocoas
      were measured. Natural cocoa powders have an extractable pH of 5.3-5.8. Alkalized
      cocoa powders were grouped into lightly treated (pH 6.50-7.20), medium-treated
      (pH 7.21-7.60), and heavily treated (pH 7.61 and higher). The natural,
      nonalkalized powders had the highest ORAC and total polyphenols and flavanols
      (including procyanidins). These chemical measurements showed a linear decrease as
      the extractable pH of the cocoa powder increased. Likewise, the flavanol
      monomers, oligomers, and polymers all showed a linear decrease with increasing pH
      of the final cocoa powder. When brown/black cocoa powders were compared to red
      cocoa powders, similar decreases in flavanols were observed with increased
      alkalization. The average total flavanol contents were 34.6 +/- 6.8 mg/g for the
      natural cocoas, 13.8 +/- 7.3 mg/g for the lightly processed cocoas, 7.8 +/- 4.0
      mg/g for the medium processed cocoas, and 3.9 +/- 1.8 mg/g for the heavily
      processed cocoa powders. The observed linear and predictable impact of
      alkalization on flavanol content is discussed with respect to other reports in
      the literature as well as what implications it may have on diet and food
      manufacturing.

PMID- 18710244
TI  - Molecular structures of gellan gum imaged with atomic force microscopy in
      relation to the rheological behavior in aqueous systems in the presence or
      absence of various cations.
AB  - Aqueous solutions of gellan gum with comparable molecular masses but with
      different acyl contents were investigated by atomic force microscopy and
      rheological measurements in the presence or absence of various cations. For a
      high-acyl sample, no continuous network structures were identified
      microscopically, except in the presence of Ca (2+), where structural
      inhomogeneity was the highest in terms of the height distribution of molecular
      assemblies. Rheological thermal hysteresis between sol-gel transitions was
      detected in the presence of K (+) and Ca (2+), particularly Ca (2+). The storage
      modulus at 20 degrees C was larger in the order Na (+) < Ca (2+) < K (+). For a
      low-acyl sample, continuous network structures were identified in the presence of
      each cation, involving greater thermal hysteresis than the corresponding data for
      the high-acyl sample. Structural homogeneity was the highest in the presence of K
      (+). Thermal hysteresis and elasticity of the system were discussed in terms of
      continuousness and homogeneity of network structures.

PMID- 18710245
TI  - Novel prediction method of beer foam stability using protein Z, barley dimeric
      alpha-amylase inhibitor-1 (BDAI-1) and yeast thioredoxin.
AB  - Foam stability is an important quality trait of beer. Our previous results of two
      dimensional gel electrophoresis (2DE) analyses of beer proteins implied a
      relationship between barley dimeric alpha-amylase inhibitor-1 (BDAI-1) and beer
      foam stability as judged by the NIBEM-T analyzer. To develop a novel prediction
      method of beer foam stability under different conditions of barley cultivar and
      malt modification, multiple linear regression analysis was applied. The spot
      intensities of major beer proteins on 2DE gel were quantified and used as
      explanatory variables. The foam stabilities of 25 beer samples each brewed from
      malt with different malt modification in one of the three cultivars (cultivars A,
      B, and C) were explained by the spot intensities of BDAI-1 at the 5% significance
      level ( r = 0.421). Furthermore, two other major protein spots (b0 and b5) were
      observed on the 2DE gels of Japanese commercial beer samples with different foam
      stability. Then, multiple regression for foam stability was calculated using
      these three spot intensities as explanatory variables. As a result, 72.1% of the
      beer foam stability in 25 beer samples was explained by a novel multiple
      regression equation calculated using spot b0 and BDAI-1 as positive explanatory
      variables and spot b5 as a negative variable. To verify the validity of the
      multiple regression equation and the explanatory variables, the beer foam
      stability in practical beer samples was analyzed. As a result, 81.5% of the beer
      foam stability in 10 Japanese commercial beer samples was also explained by using
      spot b0 and BDAI-1 as positive explanatory variables and spot b5 as a negative
      variable. Mass spectrometry analyses followed by database searches revealed that
      protein spots b0 and b5 were identified as protein Z originated from barley and
      thioredoxin originated from yeast, respectively. These results confirm that BDAI
      1 and protein Z are foam-positive factors and identify yeast thioredoxin as a
      possible novel foam-negative factor.

PMID- 18710246
TI  - Group B saponins in soy products in the U.S. Department of Agriculture--Iowa
      State University isoflavone database and their comparison with isoflavone
      contents.
AB  - Isoflavones in soy protein foods are thought to contribute to the cholesterol
      lowering effect observed when these products are fed to humans. The group B
      saponins are another ethanol-soluble phytochemical fraction associated with soy
      proteins and isoflavones and have also been associated with cholesterol-lowering
      abilities. We measured the group B soyasaponin concentrations in a variety of soy
      foods and ingredients in the U.S. Department of AgricultureIowa State University
      Isoflavone Database. We compared the isoflavone and soy saponin concentrations
      and distributions in intact soybeans, soy ingredients, and retail soy foods.
      Group B saponins occur in six predominant forms. There appears to be no
      correlation between saponin and isoflavone concentrations in intact soybeans
      ranging from 5 to 11 mumol isoflavones/g soybean and from 2 to 6 mumol saponin/g
      soybean. Depending upon the type of processing, soy ingredients have quite
      different saponins/isoflavones as compared to mature soybeans. In soy foods, the
      saponin:isoflavone ration ranges from 1:1 to 2:5, whereas in soy protein
      isolates, the ratio is approximately 5:3. Ethanol-washed ingredients have very
      low saponins and isoflavones. These very different distributions of saponins and
      isoflavones in soy products may affect how we view the outcome of feeding trials
      examining a variety of protective effects associated with soy consumption.

PMID- 18710247
TI  - Beta-cyclodextrins as carriers of monoterpenes into the hemolymph of the honey
      bee (Apis mellifera) for integrated pest management.
AB  - The Varroa mite ( Varroa destructor) is becoming ubiquitous worldwide and is a
      serious threat to honey bees. The cultivation of certain food crops are at risk.
      The most noted acaricides against Varroa mites are tau-fluvaninate and coumaphos,
      but the mites are showing resistance. Since these insecticides are used in the
      proximity of honey, it is desirable to use natural alternatives. Monoterpenoids
      such as thymol and carvacrol, that are constituents of oil of thyme and oil of
      origanum, show promise as acaricides against the Varroa mite ( Varroa
      destructor), but the delivery of these compounds remains a challenge due to the
      low water solubility and uncontrolled release into the colony. Beta-cyclodextrin
      (beta-CD) inclusion complexes of thymol, oil of origanum, and carvacrol were
      prepared on a preparative scale. Competitive binding was studied by fluorescence
      spectroscopy by using 6- p-toluidinylnaphthalene-2-sulfonate as a fluorescent
      probe. The complexes were characterized, and the competitive binding described by
      (1)H and (13)C NMR spectroscopy chemical shifts. The toxicity of beta-CD and the
      prepared complexes in enriched sucrose syrup was studied by conducting caged
      honey bee ( Apis mellifera) feeding trials. After the first and second weeks of
      feeding, hemolymph and gut tissue samples were acquired from the caged bee study.
      The levels of thymol and carvacrol were quantified by solid-phase microextraction
      gas chromatography mass spectroscopy, using an optimized procedure we developed.
      High (mM) levels of thymol and carvacrol were detected in bee tissues without any
      imposed toxicity to the bees, in an effort to deter Varroa mites from feeding on
      honey bee hemolymph.

PMID- 18710248
TI  - Effects of black soybean [Glycine max (L.) Merr.] seed coats and its
      anthocyanidins on colonic inflammation and cell proliferation in vitro and in
      vivo.
AB  - Anti-inflammatory and antiproliferative activities of anthocyanidins and
      anthocyanin-rich black soybean seed coats were studied in HT-29 human colon
      adenocarcinoma cells and carcinogen-treated F344 rats, respectively. Cyanidin and
      delphinidin significantly inhibited cell growth at concentrations of >or=1
      microM. Anthocyanidins suppressed cyclooxygenase-2 (COX-2) and inducible nitric
      oxide synthase (iNOS) mRNAs in TPA-stimulated HT-29 cells. Both yellow and black
      soybean seed coat supplementation (10%, w/w) did not significantly reduce the
      number of aberrant crypt foci (ACF), although a modest decrease in the number of
      ACF was observed in animals fed soybean seed coats. The colonic COX-2 mRNA level
      was suppressed in rats fed both soybean seed coat diet. The plasma prostaglandin
      E 2 (PGE 2) level was reduced only in rats fed black soybean seed coats. No
      difference was observed in either colonic iNOS mRNA or plasma nitric oxide level.
      These results indicate that anthocyanidins are possible anti-inflammatory agents;
      however, further studies are required to determine required intake levels in vivo
      to exert antitumor effect.

PMID- 18710249
TI  - Quantitative reconstruction of the nonvolatile sensometabolome of a red wine.
AB  - The first comprehensive quantitative determination of 82 putative taste-active
      metabolites and mineral salts, the ranking of these compounds in their sensory
      impact based on dose-over-threshold (DoT) factors, followed by the confirmation
      of their sensory relevance by taste reconstruction and omission experiments
      enabled the decoding of the nonvolatile sensometabolome of a red wine. For the
      first time, the bitterness of the red wine could be demonstrated to be induced by
      subthreshold concentrations of phenolic acid ethyl esters and flavan-3-ols.
      Whereas the velvety astringent onset was imparted by three flavon-3-ol glucosides
      and dihydroflavon-3-ol rhamnosides, the puckering astringent offset was caused by
      a polymeric fraction exhibiting molecular masses above >5 kDa and was found to be
      amplified by the organic acids. The perceived sourness was imparted by l-tartaric
      acid, d-galacturonic acid, acetic acid, succinic acid, l-malic acid, and l-lactic
      acid and was slightly suppressed by the chlorides of potassium, magnesium, and
      ammonium, respectively. In addition, d-fructose and glycerol as well as
      subthreshold concentrations of glucose, 1,2-propandiol, and myo-inositol were
      found to be responsible for the sweetness, whereas the mouthfulness and body of
      the red wine were induced only by glycerol, 1,2-propandiol, and myo-inositol.

PMID- 18710250
TI  - Dose-dependent absorption, metabolism, and excretion of genistein in rats.
AB  - Genistein (4',5,7-trihydroxyisoflavone), a naturally occurring phenolic compound,
      possesses well-known preventive activity in breast and prostate cancer,
      cardiovascular diseases, and postmenopausal problems. The aim of this study is to
      investigate the distribution and dose-dependent absorption, metabolism, and
      excretion of genistein in rats. Genistein was orally administered to rats at
      different doses. At various time intervals, blood, bile, and urine samples were
      collected and incubated with glucuronidase to hydrolyze the glucuronidated
      genistein. Genistein was detected by HPLC. High levels of glucuronidated
      genistein were detected in the plasma, bile, and urine after genistein
      administration. When genistein was administered to rats at 6.25, 12.5, and 50 mg
      x kg (-1) doses, the AUC (0- t) values for genistein were 23.5, 80.9, and 177.9
      mg x min x L (-1); the oral absolute bioavailabilities were 21.9, 33.5, and
      19.0%; the AUC (0- t) values of glucuronidated genistein were 173.8, 470.7, and
      1721.2 mg x min x L (-1), respectively. The cumulative biliary excretion of
      genistein respective to each dose was 42.6 +/- 6.5, 75.2 +/- 18.9, and 126.6 +/-
      34.8 microg; the cumulative biliary excretion of glucuronidated genistein was
      108.5 +/- 35.2, 423.5 +/- 158.3, and 853.7 +/- 320.8 microg for each dose,
      respectively. The cumulative urinary excretion of genistein was 34.8 +/- 10.8,
      187.3 +/- 67.0 and 213.6 +/- 30.6 microg for each dose, respectively; the
      cumulative levels of glucuronidated genistein excreted in the urine were 217.8 +/
      52.1, 583.1 +/- 106.9, and 1108.4 +/- 88.1 microg, respectively. These results
      indicated that at high doses absorption, biotransformation, and excretion of
      genistein occurred in a nonlinear dose-dependent manner. Therefore, the results
      of these pharmacokinetic studies raise important questions about the therapeutic
      significance of consuming large quantities of genistein, genistein analogues, or
      soy-based neutraceuticals.

PMID- 18710251
TI  - Acute toxicity of high doses of the glycoalkaloids, alpha-solanine and alpha
      chaconine, in the Syrian Golden hamster.
AB  - Sprouted, stressed, or spoiled potato tubers have reportedly led to human acute
      intoxication, coma, and death when consumed in high amounts. These effects have
      been attributed to glycoalkaloids (GAs), primarily alpha-solanine and alpha
      chaconine, naturally present in all potatoes. The level of GAs in potato tubers
      has previously been shown to increase substantially as a result of improper
      handling and postharvest storage. A short-term study was performed to investigate
      the dose-response profile of alpha-solanine and alpha-chaconine alone or in
      combination, administered daily by oral gavage to Syrian Golden hamsters. Daily
      doses of 100 mg of alpha-solanine [kg body weight (BW)] (-1) induced death in two
      of four hamsters within 4 days, when administered by gavage to female Syrian
      hamsters. Doses of 100 mg of alpha-chaconine alone or alpha-solanine and alpha
      chaconine combined in a ratio of 1:2.5, in doses of 75 or 100 mg (kg BW) (-1),
      induced death in one of four hamsters within the same period. Animals dosed with
      alpha-solanine alone or in combination with alpha-chaconine suffered from fluid
      filled and dilated small intestines. The GA administration had no effect on
      acetyl cholinesterase (AChE) or butyryl cholinesterase (BuChE) activity in plasma
      or brain. Liquid chromatography-mass spectrometry-based metabolomics showed that
      there was a specific accumulation of alpha-chaconine in the liver tissues. In
      addition, metabolomics gave direct evidence of glycolytic metabolism of the GA
      with the beta 1, beta 2, and gamma-GAs detected in the urine and, to a lesser
      extent, the feces. Doses from 75 mg (kg BW) (-1) of alpha-chaconine, alpha
      solanine, or the two compounds combined were potentially lethal within 4-5 days
      in the Syrian Golden hamster. However, the cause of death in these studies could
      not be established. No synergistic effects of alpha-solanine combined with alpha
      chaconine were evident.

PMID- 18710252
TI  - Stress-induced biosynthesis of dicaffeoylquinic acids in globe artichoke.
AB  - Leaf extracts from globe artichoke ( Cynara cardunculus L. var. scolymus) have
      been widely used in medicine as hepatoprotectant and choleretic agents. Globe
      artichoke leaves represent a natural source of phenolic acids with
      dicaffeoylquinic acids, such as cynarin (1,3-dicaffeoylquinic acid), along with
      its biosynthetic precursor chlorogenic acid (5-caffeoylquinic acid) as the most
      abundant molecules. This paper reports the development of an experimental system
      to induce caffeoylquinic acids. This system may serve to study the regulation of
      the biosynthesis of (poly)phenolic compounds in globe artichoke and the genetic
      basis of this metabolic regulation. By means of HPLC-PDA and accurate mass LC
      QTOF MS and MS/MS analyses, the major phenolic compounds in globe artichoke
      leaves were identified: four isomers of dicaffeoylquinic acid, three isomers of
      caffeoylquinic acid, and the flavone luteolin 7-glucoside. Next, plant material
      was identified in which the concentration of phenolic compounds was comparable in
      the absence of particular treatments, with the aim to use this material to test
      the effect of stress application on the regulation of biosynthesis of
      caffeoylquinic acids. Using this material, the effect of UV-C, methyl jasmonate,
      and salicylic acid treatments on (poly)phenolic compounds was tested in different
      globe artichoke genotypes. UV-C exposure consistently increased the levels of
      dicaffeoylquinic acids in all genotypes, whereas the effect on compounds from the
      same biosynthetic pathway, for example, chlorogenic acid and luteolin-7
      glucoside, was much less pronounced and was not statistically significant. No
      effect of methyl jasmonate or salicylic acid was found. Time-response experiments
      indicated that the level of dicaffeoylquinic acids reached a maximum at 24 h
      after UV radiation. On the basis of these results a role of dicaffeoylquinic
      acids in UV protection in globe artichoke is hypothesized.

PMID- 18710253
TI  - Simultaneous confirmatory analysis of different transgenic maize (zea mays) lines
      using multiplex polymerase chain reaction-restriction analysis and capillary gel
      electrophoresis with laser induced fluorescence detection.
AB  - A novel analytical procedure based on the combination of multiplex PCR,
      restriction analysis, and CGE-LIF to unambiguosly and simultaneously confirm the
      presence of multiple lines of genetically modified corn is proposed. This
      methodology is based on the amplification of event-specific DNA regions by
      multiplex PCR using 6-FAM-labeled primers. Subsequently, PCR products are
      digested by a mixture containing specific restriction endonucleases. Thus,
      restriction endonucleases selectively recognize DNA target sequences contained in
      the PCR products and cleave the double-stranded DNA at a given cleavage site.
      Next, the restriction digest is analyzed by CGE-LIF corroborating the length of
      the expected restriction fragments, confirming (or not) the existence of GMOs.
      For accurate size determination of the DNA fragments by CGE-LIF a special
      standard DNA mixture was produced in this laboratory for calibration. The
      suitability of this mixture for size determination of labeled DNA fragments is
      also demonstrated. The usefulness of the proposed methodology is demonstrated
      through the simultaneous detection and confirmatory analysis of samples
      containing 0.5% of GA21 and MON863 maize plus an endogenous gene of maize as
      control.

PMID- 18710254
TI  - Acid-degradable polyurethane particles for protein-based vaccines: biological
      evaluation and in vitro analysis of particle degradation products.
AB  - Acid-degradable particles containing a model protein antigen, ovalbumin, were
      prepared from a polyurethane with acetal moieties embedded throughout the
      polymer, and characterized by dynamic light scattering and transmission electron
      microscopy. The small molecule degradation byproduct of the particles was
      synthesized and tested in vitro for toxicity indicating an LC 50 of 12,500
      microg/mL. A new liquid chromatography-mass spectrometry technique was developed
      to monitor the in vitro degradation of these particles. The degradation byproduct
      inside RAW macrophages was at its highest level after 24 h of culture and was
      efficiently exocytosed until it was no longer detectable after 4 days. When
      tested in vitro, these particles induced a substantial increase in the
      presentation of the immunodominant ovalbumin-derived peptide SIINFEKL in both
      macrophages and dendritic cells. In addition, vaccination with these particles
      generated a cytotoxic T-lymphocyte response that was superior to both free
      ovalbumin and particles made from an analogous but slower-degrading acid-labile
      polyurethane polymer. Overall, we present a fully degradable polymer system with
      nontoxic byproducts, which may find use in various biomedical applications
      including protein-based vaccines.

PMID- 18710255
TI  - Computational model for predicting chemical substituent effects on passive drug
      permeability across parallel artificial membranes.
AB  - Drug permeability is often a limiting step in drug action, requiring chemical
      optimization of a drug candidate to improve this property. Such optimization is
      typically performed in the context of a congeneric series, where substituents are
      varied to optimize the target property. Motivated by this need the present work
      examines the influence of chemical substituents on passive permeability (log P
      pass) across parallel artificial membranes (PAMPA) undertaken for three
      congeneric series of compounds; benzoic acids, pyridines and quinolines. PAMPA
      showed pyridine and quinoline to have high permeability and chemical substituents
      to typically reduce the permeability. On the contrary, benzoic acid showed poor
      permeability and chemical substituents typically increased the permeability. To
      quantitate these effects with respect to physical properties, models were built
      to explain and predict the permeability of these classes of compounds based on
      computed molecular descriptors. Models for the benzoic acid series in the ionized
      state indicated the solvent accessible surface area, cavity dispersion and the
      free energy of solvation in hexane as well as in water to dominate permeability.
      However, when the acid group is treated as neutral, the free energy of solvation
      in water, the fraction polar surface area, the polar surface area and difference
      in the free energy of solvation between hexane and water were important; these
      terms, among others, were also important for the neutral pyridine-quinoline
      series. Considering that the permeability of the benzoic acid series is about 2
      orders of magnitude lower than the pyridines and quinolines and that a shift of
      approximately two pH units in the p K a of the acid group of benzoic acid will
      allow for the neutral species of the molecule to dominate under experimental
      conditions (pH = 6.5), these results suggest that the additional energy barrier
      associated with permeation of the benzoic acid series is associated with the need
      to protonate the acidic group, thereby forming the neutral species which may then
      cross the hydrophobic region of the membrane.

PMID- 18710256
TI  - Stabilization of tetanus toxoid encapsulated in PLGA microspheres.
AB  - Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid)
      (PLGA) microspheres is a novel approach to reduce the number of antigen doses
      required for protection against infection. A major impediment to developing
      single-shot vaccines is encapsulated antigen instability during months of
      exposure to physiological conditions. For example, efforts to control neonatal
      tetanus in developing countries with a single-dose TT vaccine based on PLGA
      microspheres have been plagued by poor stability of the 150 kDa formaldehyde
      detoxified protein antigen, tetanus toxoid (TT), in the polymer. We examined the
      denatured states of PLGA-encapsulated TT, revealing two primary TT instability
      mechanisms: (1) protein aggregation mediated by formaldehyde and (2) acid-induced
      protein unfolding and epitope damage. Further, we systematically identified
      excipients, which can efficiently inhibit TT aggregation and retain TT
      antigenicity under simulated deleterious conditions, i.e., elevated temperature
      and humidity. By employing these novel additives in the PLGA system, we report
      the slow and continuous release of high doses of TT for one month with retained
      antigen stability during bioerosion of PLGA.

PMID- 18710257
TI  - Protein nanopatterns for improved immunodetection sensitivity.
AB  - In this work, we clearly demonstrate the capability of protein nanopatterns of
      improving the quality factors of immunosensing devices, such as lowering of the
      limit of detection and increase of sensitivity. This beneficial effect is
      obtained by the formation on the sensor's surface of bioadhesive domains of
      nanometric dimensions in a nonadhesive matrix by means of colloidal lithography.

PMID- 18710258
TI  - Use of a solution cathode glow discharge for cold vapor generation of mercury
      with determination by ICP-atomic emission spectrometry.
AB  - A novel vapor-generation technique is described for mercury determination in
      aqueous solutions. Without need for a chemical reducing agent, dissolved mercury
      species are converted to volatile Hg vapor in a solution cathode glow discharge.
      The generated Hg vapor is then transported to an inductively coupled plasma for
      determination by atomic emission spectrometry. Mercury vapor is readily generated
      from a background electrolyte containing 0.1 M HNO 3. Vapor generation efficiency
      was found to be higher by a factor of 2-3 in the presence of low molecular weight
      organic acids (formic or acetic acids) or alcohols (ethanol). Optimal conditions
      for discharge-induced vapor generation and reduced interference from concomitant
      inorganic ions were also identified. However, the presence of chloride ion
      reduces the efficiency of Hg-vapor generation. In the continuous sample
      introduction mode, the detection limit was found to be 0.7 microg L (-1), and
      repeatability was 1.2% RSD ( n = 11) for a 20 microg L (-1) standard. In
      comparison with other vapor generation methods, it offers several advantages:
      First, it is applicable to both inorganic and organic Hg determination; organic
      mercury (thiomersal) can be directly transformed into volatile Hg species without
      the need for prior oxidation. Second, the vapor-generation efficiency is high;
      the efficiency (with formic acid as a promoter) is superior to that of
      conventional SnCl 2-HCl reduction. Third, the vapor generation is extremely rapid
      and therefore is easy to couple with flow injection. The method is sensitive and
      simple in operation, requires no auxiliary reagents, and serves as a useful
      alternative to conventional vapor generation for ultratrace Hg determination.

PMID- 18710259
TI  - Analysis of major protein-protein and protein-metal complexes of erythrocytes
      directly from cell lysate utilizing capillary electrophoresis mass spectrometry.
AB  - The separation and detection of the major protein-protein and protein-metal
      complexes of erythrocytes directly from cell lysate under native conditions has
      been accomplished for the first time using capillary electrophoresis electrospray
      ionization-mass spectrometry (CE/ESI-MS). All three major protein-protein and
      protein-metal complexes in human red blood cells (RBCs) with a concentration
      dynamic range of approximately 3 orders of magnitude were successfully detected.
      Intact complexes detected in lysed RBCs included carbonic anhydrase II (CAII-Zn
      at approximately 0.8 amol/cell) complexed with its zinc cofactor, carbonic
      anhydrase I (CAI-Zn at approximately 7 amol/cell) complexed with its zinc
      cofactor, and hemoglobin A (Hb-tetramer at approximately 450 amol/cell)a tetramer
      formed by two alpha-beta-subunits and four heme groups. The average molecular
      weights measured for these complexes were consistent with their theoretical
      values within 0.01% mass accuracy. The use of Polybrene as a self-coating reagent
      in conjunction with ammonium acetate at pH approximately 7.4, narrow capillary
      for high separation efficiency, and forward polarity CE to avoid acid production
      at the tip of the capillary were overriding experimental factors for successful
      analysis of protein complexes. Diluting the lysed blood sample in ammonium
      acetate for a minimum of 6 h before injecting the sample into the CE was
      essential for obtaining the mass accuracy consistent with their theoretical
      average molecular weights. At physiological pH, the mass spectrum of the
      electrophoretic peak of Hb-tetramer included a small amount of the monomers and
      Hb-dimer. The migration time and peak profile of these species were almost
      identical to that of the tetramer, indicating that they are formed from
      decomposition of the Hb-tetramer during the ESI process. A separate
      electrophoretic peak for the Hb-dimer was only detected when the pH of the BGE
      was lowered from 7.4 to approximately 6.6. Running CE in forward polarity mode
      was essential for detection of the intact Hb-tetramer as well as CAI-Zn and CAII
      Zn complexes. Under forward polarity mode, CE outlet/ESI shared electrode acts as
      the cathode of the CE circuit and the anode (positive voltage for positive ions)
      of the ESI circuit, thereby maintaining approximately neutral pH at the CE
      outlet/ESI electrode. In addition, under forward polarity mode, CAII-Zn and CAI
      Zn migrated ahead of Hb-tetramer, avoiding being masked by 562x and 64x,
      respectively, molar excess of Hb-tetramer.

PMID- 18710260
TI  - Overexpression and functional characterization of the extracellular domain of the
      human alpha1 glycine receptor.
AB  - A novel truncated form (residues 1-214, with a randomized C-terminal tail) of the
      ligand-binding extracellular domain (ECD) of the human alpha1 glycine receptor
      (GlyR), with amino acids from the corresponding sequence of an acetylcholine
      binding protein (AChBP) substituted for two relatively hydrophobic membrane
      proximal loops, was overexpressed using a baculovirus expression system. The
      mutant GlyR ECD, named GlyBP, was present in both soluble and membrane-associated
      fractions after cell lysis, though only the latter appeared to be in a native
      like conformation capable of binding strychnine, a GlyR specific antagonist. The
      membrane-associated GlyBP was solubilized, and detergent/lipid/protein micelles
      were affinity purified. After detergent removal, GlyBP may be isolated in either
      aqueous or vesicular form. Binding assays and spectroscopic studies using
      circular dichroism and FRET are consistent with both forms adopting equivalent
      native-like conformations. Thus, GlyBP may be isolated as a soluble or membrane
      associated assembly that serves as a structural and functional homologue of the
      ECD of GlyR.

PMID- 18710261
TI  - Mechanistic and structural analysis of aminoglycoside N-acetyltransferase AAC(6')
      Ib and its bifunctional, fluoroquinolone-active AAC(6')-Ib-cr variant.
AB  - Enzymatic modification of aminoglycoside antibiotics mediated by regioselective
      aminoglycoside N-acetyltransferases is the predominant cause of bacterial
      resistance to aminoglycosides. A recently discovered bifunctional aminoglycoside
      acetyltransferase (AAC(6')-Ib variant, AAC(6')-Ib-cr) has been shown to catalyze
      the acetylation of fluoroquinolones as well as aminoglycosides. We have expressed
      and purified AAC(6')-Ib-wt and its bifunctional variant AAC(6')-Ib-cr in
      Escherichia coli and characterized their kinetic and chemical mechanism. Initial
      velocity and dead-end inhibition studies support an ordered sequential mechanism
      for the enzyme(s). The three-dimensional structure of AAC(6')-Ib-wt was
      determined in various complexes with donor and acceptor ligands to resolutions
      greater than 2.2 A. Observation of the direct, and optimally positioned,
      interaction between the 6'-NH 2 and Asp115 suggests that Asp115 acts as a general
      base to accept a proton in the reaction. The structure of AAC(6')-Ib-wt permits
      the construction of a molecular model of the interactions of fluoroquinolones
      with the AAC(6')-Ib-cr variant. The model suggests that a major contribution to
      the fluoroquinolone acetylation activity comes from the Asp179Tyr mutation, where
      Tyr179 makes pi-stacking interactions with the quinolone ring facilitating
      quinolone binding. The model also suggests that fluoroquinolones and
      aminoglycosides have different binding modes. On the basis of kinetic properties,
      the pH dependence of the kinetic parameters, and structural information, we
      propose an acid/base-assisted reaction catalyzed by AAC(6')-Ib-wt and the AAC(6')
      Ib-cr variant involving a ternary complex.

PMID- 18710262
TI  - Amylin proprotein processing generates progressively more amyloidogenic peptides
      that initially sample the helical state.
AB  - Human amylin, or islet amyloid polypeptide, is a peptide cosecreted with insulin
      by the beta cells of the pancreatic islets of Langerhans. The 37-residue, C
      terminally amidated human amylin peptide derives from a proprotein that undergoes
      disulfide bond formation in the endoplasmic reticulum and is then subjected to
      four enzymatic processing events in the immature secretory granule. Human amylin
      forms both intracellular and extracellular amyloid deposits in the pancreas of
      most type II diabetic subjects, likely reflecting compromised secretory cell
      function. In addition, amylin processing intermediates, postulated to initiate
      intracellular amyloidogenesis, have been reported as components of intracellular
      amyloid in beta cells. We investigated the amyloidogenicity of amylin and its
      processing intermediates in vitro. Chaotrope-denatured amylin and amylin
      processing intermediates were subjected to size exclusion chromatography,
      affording high concentrations of monomeric peptides. NMR studies reveal that
      human amylin samples helical conformations. Under conditions mimicking the
      immature secretory granule (37 degrees C, pH 6), amylin forms amyloid aggregates
      more rapidly than its processing intermediates, and more rapidly than its reduced
      counterparts. Our studies also show that the amyloidogenicity of amylin and its
      processing intermediates is negatively correlated with net charge and charge at
      the C-terminus. Although our conditions may not precisely reflect those of
      amyloidogenesis in vivo, the lower amyloidogenicity of the processing
      intermediates relative to amylin suggests their presence in intracellular amyloid
      deposits in the increasingly stressed beta cells of diabetic subjects may be a
      consequence of general defects in protein homeostasis control known to occur in
      diabetes rather than serving as amyloid initiators.

PMID- 18710263
TI  - Binding synergy and cooperativity in dihydrodipicolinate reductase: implications
      for mechanism and the design of biligand inhibitors.
AB  - Dihydrodipicolinate reductase (DHPR) is a homotetramer that catalyzes reduction
      of dihydrodipicolinate (DHP). We recently reported a biligand inhibitor ( K i =
      100 nM) of DHPR, comprised of fragments that bind in the NADH (CRAA = catechol
      rhodanine acetic acid) and DHP (PDC = pyridine dicarboxylate) binding sites.
      Herein, we characterize binding synergy and cooperativity for ligand binding to
      Escherichia coli DHPR: NADH or CRAA and PDC (stable analog of DHP). While K d
      values indicate little synergy between NADH and PDC, (1)H- (15)N HSQC chemical
      shift perturbation and saturation transfer difference (STD) titrations indicate
      that PDC induces a more dramatic conformational change than NADH, consistent with
      a role in domain closure. PDC binds cooperatively (Hill coefficient = 2), while
      NADH does not, based on STD titrations that monitor only fast exchange processes.
      However, HSQC titrations monitoring Trp253 (located between monomers) indicate
      that NADH binds in two steps, with high affinity binding to only one of the
      monomers. Therefore, DHPR binds cofactor via a sequential model, with negative
      cooperativity. These results, interpreted in light of steady-state data, suggest
      that DHPR activity requires NADH binding at only one of the four monomers.
      Implications of our results for fragment assembly are discussed, using CRAA
      tethering to PDC as a model biligand: (a) if one fragment (ex. PDC) must induce a
      large structural change before the other fragment is brought proximal, this must
      be screened for upfront, and (b) cooperative or synergistic interactions between
      binding sites can lead to unexpected and misleading effects in NMR-based
      screening.

PMID- 18710264
TI  - Copper oxide nanoparticles are highly toxic: a comparison between metal oxide
      nanoparticles and carbon nanotubes.
AB  - Since the manufacture and use of nanoparticles are increasing, humans are more
      likely to be exposed occupationally or via consumer products and the environment.
      However, so far toxicity data for most manufactured nanoparticles are limited.
      The aim of this study was to investigate and compare different nanoparticles and
      nanotubes regarding cytotoxicity and ability to cause DNA damage and oxidative
      stress. The study was focused on different metal oxide particles (CuO, TiO2, ZnO,
      CuZnFe2O4, Fe3O4, Fe2O3), and the toxicity was compared to that of carbon
      nanoparticles and multiwalled carbon nanotubes (MWCNT). The human lung epithelial
      cell line A549 was exposed to the particles, and cytotoxicity was analyzed using
      trypan blue staining. DNA damage and oxidative lesions were determined using the
      comet assay, and intracellular production of reactive oxygen species (ROS) was
      measured using the oxidation-sensitive fluoroprobe 2',7'-dichlorofluorescin
      diacetate (DCFH-DA). The results showed that there was a high variation among
      different nanoparticles concerning their ability to cause toxic effects. CuO
      nanoparticles were most potent regarding cytotoxicity and DNA damage. The
      toxicity was likely not explained by Cu ions released to the cell medium. These
      particles also caused oxidative lesions and were the only particles that induced
      an almost significant increase (p = 0.058) in intracellular ROS. ZnO showed
      effects on cell viability as well as DNA damage, whereas the TiO2 particles (a
      mix of rutile and anatase) only caused DNA damage. For iron oxide particles
      (Fe3O4, Fe2O3), no or low toxicity was observed, but CuZnFe2O4 particles were
      rather potent in inducing DNA lesions. Finally, the carbon nanotubes showed
      cytotoxic effects and caused DNA damage in the lowest dose tested. The effects
      were not explained by soluble metal impurities. In conclusion, this study
      highlights the in vitro toxicity of CuO nanoparticles.

PMID- 18710265
TI  - Chain conformation of poly(dimethyl siloxane) at the air/water interface by sum
      frequency generation.
AB  - This is to report a study of chain conformation of poly(dimethylsiloxane) (PDMS)
      in spread monolayers at the air/water interface (A/W) with the aid of vibrational
      sum frequency spectroscopy (VSFS). We find that methyl groups of PDMS chains at
      the interface are completely disordered in the dilute regime of the surface
      density. At higher surface densities, however, the two methyl groups on the
      repeating unit point into the air asymmetrically; one points more normal to the
      interface, whereas the other lies more parallel to the interface. In the first
      collapsed regime, where the surface pressure of the PDMS monolayer reaches a
      plateau value of 8.7 mN/m, the signal intensity at 2915 cm (-1), assigned to the
      symmetric vibrational frequency of the methyl groups, is found independent of the
      surface density. On the basis of this finding, we propose that PDMS chains, in
      the first collapse regime at the A/W, form asymmetric layers. Thus, our proposal
      lends support to earlier works by Langevin's group to refute a widely speculated
      helix model that was based on energy minimization in the crystalline state of
      PDMS. In short, the energy consideration in the bulk crystalline state does not
      provide meaningful guidance as to the chain conformation of the monolayer at the
      A/W.

PMID- 18710266
TI  - Ultrasonic synthesis of stable, functional lysozyme microbubbles.
AB  - High-intensity ultrasound induces emulsification and cross-linking of protein
      molecules in aqueous medium. The stability and the functionality of the resultant
      protein-coated microbubbles are crucial in many of their applications. For
      example, the stability of drug-loaded microbubbles should be sufficiently long
      enough, in vivo, so that they can be ruptured only at specific sites for release
      of the drugs. In this study, we report the synthesis of stable and functional
      microbubbles, coated with chemically reduced lysozyme, using high-intensity
      ultrasound in aqueous solution. In the absence of chemical reduction, stable
      microbubbles were not produced with native lysozyme, indicating the importance of
      free -SH functional groups for protein cross-linking. The degree of cross-linking
      between lysozyme molecules was controlled by manipulating both the extent of
      chemical reduction of the intramolecular disulfide bonds and sonication time. The
      lysozyme-coated microbubbles are stable for several months and retain the
      enzymatic (antimicrobial) activity of lysozyme. The layer-by-layer (LbL)
      deposition of polyelectrolytes onto the protein-shell air-core template has been
      used as a versatile procedure to modify the surface properties of the
      microbubbles, indicating the possibility of adsorbing potential drugs and/or
      biolabels on the surface of these microbubbles for therapeutic and diagnostic
      applications.

PMID- 18710267
TI  - NMR diffusometry with beds of nanoporous host particles: an assessment of mass
      transfer in compartmented two-phase systems.
AB  - Molecular diffusion in a bed of zeolite crystallites is mimicked by dynamic Monte
      Carlo simulation of a particle hopping on a two-dimensional square lattice. The
      resulting probability distribution of molecular propagation (the "mean
      propagator") is used for a rigorous determination of the resulting dependencies
      of diffusion measurement by pulsed field gradient NMR. In the limiting cases of
      intracrystalline, restricted, and long-range diffusion, these dependencies are
      found to coincide with the well-known relations resulting from the application of
      a simplifying exchange model (the "two-region" approximation). The intensity of
      transport resistances on the boundary between the intra- and intercrystalline
      spaces, i.e., on the compartment boundaries, is only accessible in the
      intermediate case, i.e., for observation times comparable with the mean lifetimes
      within the different compartments. In this case, significant differences between
      the results of the rigorous treatment and the "two-region" approximation may
      occur.

PMID- 18710269
TI  - Film-forming microgels for pH-triggered capture and release.
AB  - The pH-responsive behavior for a series of lightly cross-linked, sterically
      stabilized poly(tertiary amine methacrylate)-based latexes adsorbed onto mica and
      silica was investigated using in situ tapping mode AFM at room temperature. The
      adsorbed layer structure was primarily determined by the glass transition
      temperature, T(g), of the latex: poly[2-(diethylamino)ethyl methacrylate]-based
      particles coalesced to form relatively featureless uniform thin films, whereas
      the higher T(g) poly[2-(diisopropylamino)ethyl methacrylate] latexes retained
      their original particulate character. Adsorption was enhanced by using a cationic
      poly[2-(dimethylamino)ethyl methacrylate] steric stabilizer, rather than a
      nonionic poly(ethylene glycol)-based stabilizer, since the former led to stronger
      electrostatic binding to the oppositely charged substrate. Both types of adsorbed
      latexes acquired cationic microgel character and swelled appreciably at low pH,
      even those that had coalesced to form films. Fluorescence spectroscopy was used
      to study the capture of a model hydrophobic probe, pyrene, by these adsorbed
      latex layers followed by its subsequent release by lowering the solution pH. The
      repeated capture and release of pyrene through several pH cycles was also
      demonstrated. Since these poly(tertiary amine methacrylate) latexes are readily
      prepared by aqueous emulsion polymerization and adsorption occurs spontaneously
      from aqueous solution, this may constitute an attractive route for the surface
      modification of silica, mica and other oxides.

PMID- 18710268
TI  - Generic nitric oxide (NO) generating surface by immobilizing organoselenium
      species via layer-by-layer assembly.
AB  - A universal nitric oxide (NO) generating surface is assembled via Layer-by-Layer
      (LbL) deposition of sodium alginate (Alg) and organoselenium modified
      polyethyleneimine (SePEI) on quartz and polymeric substrates. The immobilized
      SePEI species is capable of catalytically decomposing S-nitrosothiol species
      (RSNO) to NO in the presence of thiol reducing agents (e.g., glutathione,
      cysteine, etc.). The stepwise buildup of the multilayer films is monitored by UV
      vis spectroscopy, SEM and surface contact angle measurements. X-ray photoelectron
      spectroscopy is used to study the stoichiometry between the polyanion and
      polycation, and also the presence of Se in the catalytic LbL film. A reductive
      annealing process is necessary to improve the stability of freshly coated
      multilayer films via chain rearrangement. Chemiluminescence measurements
      illustrate the ability of the LbL films to generate NO from S-nitrosoglutathione
      (GSNO) in the presence of glutathione (GSH). Enhanced NO fluxes can be achieved
      by increasing the number of catalytic (SePEI/Alg) bilayers coated on the
      substrates. Nitric oxide generation is observed even after prolonged contact with
      sheep whole blood. Preliminary applications of this LbL on silicone rubber
      tubings and polyurethane catheters reveal similar NO generation behavior from
      these biomedical grade polymeric substrates.

PMID- 18710270
TI  - Photochemical modification and patterning of SU-8 using anthraquinone
      photolinkers.
AB  - Bioactive protein patterns and microarrays achieved by selective localization of
      biomolecules find various applications in biosensors, bio-microelectromechanical
      systems (bio-MEMS), and in basic protein studies. In this paper we describe
      simple photochemical methods to fabricate two-dimensional patterns on a Novolac A
      derivative polymer (SU-8) and, subsequently, their functionalization with
      biomolecules. Anthraquinone (AQ) derivatives are used to chemically modify and
      pattern SU-8 surfaces. Features as small as 20 mum are obtained when using
      uncollimated light. The X-Y spatial resolution of micropatterned AQ molecules is
      improved to 1.5 mum when a collimated light source is used. This micropatterning
      process will be important for the functionalization of MEMS-based biosensors. The
      method saves several processing steps and can be integrated in cleanroom
      fabrication thus avoiding contamination of the sensor surfaces.

PMID- 18710271
TI  - Superhydrophobic and low light reflectivity silicon surfaces fabricated by
      hierarchical etching.
AB  - Silicon is employed in a variety of electronic and optical devices such as
      integrated circuits, photovoltaics, sensors, and detectors. In this paper, Au
      assisted etching of silicon has been used to prepare superhydrophobic surfaces
      that may add unique properties to such devices. Surfaces were characterized by
      contact angle and contact angle hysteresis. Superhydrophobic surfaces with
      reduced hysteresis were prepared by Au-assisted etching of pyramid-structured
      silicon surfaces to generate hierarchical surfaces. Consideration of the Laplace
      pressure on hydrophobized hierarchical surfaces gives insight into the manner by
      which contact is established at the liquid/composite surface interface. Light
      reflectivity from the etched surfaces was also investigated to assess application
      of these structures to photovoltaic devices.

PMID- 18710272
TI  - On the formation and structure of nanometric polyhedral foams: toward the dry
      limit.
AB  - High surface area, high porosity, nanometric polygonal silica foams with
      hierarchically connected and uniformly sized pore systems are reported here. We
      observe a remarkable increase in foam cell sizes from mesoscopic to macroscopic
      dimensions upon swelling the self-assembled template with oil. The resultant
      structures resemble classical macroscopic soap foams and display, among other
      features, Plateau borders and volume fractions approaching the dry limit of 100%.
      In well-developed foams of this kind, dimensionally isometric polyhedral cells
      are connected by relatively short, flat cylindrical mesopores through polyhedral
      faces and micropores through the walls. For one sample, with approximately 75 nm
      diameter primary foam cells, we infer three separate sets of cell-connecting
      mesopores puncturing tetragonal, pentagonal, and hexagonal faces of the component
      polyhedra. A multiple step model of foam formation is discussed where an organic
      silica precursor progressively hydrolyzes and condenses as a growing flexible
      shell from the core-corona interface of oil-swollen triblock copolymer micelles
      or microemulsion droplets, inducing a clouding phenomena in the otherwise
      stabilizing poly(ethylene oxide) chains, leading to aggregation, deformation, and
      jamming to high volume fractions.

PMID- 18710273
TI  - Peptide-targeted polyglutamic acid doxorubicin conjugates for the treatment of
      alpha(v)beta(6)-positive cancers.
AB  - Most chemotherapeutics exert their effects on tumor cells as well as their
      healthy counterparts, resulting in dose limiting side effects. Cell-specific
      delivery of therapeutics can increase the therapeutic window for treatment by
      maintaining the therapeutic efficacy while decreasing the untoward side effects.
      We have previously identified a peptide, named H2009.1, which binds to the
      integrin alpha(v)beta(6). Here, we report the synthesis of a peptide targeted
      polyglutamic acid polymer in which the high affinity alpha(v)beta(6)-specific
      tetrameric H2009.1 peptide is incorporated via a thioether at the N-terminus of a
      15 amino acid polymer of glutamic acid. Doxorubicin is incorporated into the
      polymer via an acid-labile hydrazone bond. Payloads of four doxorubicin molecules
      per targeting agent are achieved. The drug is released at pH 4.0 and 5.6 but the
      conjugate is stable at pH 7.0. The conjugate is selectively internalized into
      alpha(v)beta(6) positive cells as witnessed by flow cytometric analysis and
      fluorescent microscopy. Cellular uptake is mediated by the H2009.1 peptide, as no
      internalization of the doxorubicin-PG polymer is observed when it is conjugated
      to a scrambled sequence control peptide. Importantly, the conjugate is more
      cytotoxic toward a targeted cell than a cell line that does not express the
      integrin.

PMID- 18710275
TI  - Anomalously increased lifetimes of biological complexes at zero force due to the
      protein-water interface.
AB  - A number of biological bonds show dramatically increased lifetimes at zero-force
      conditions, compared to lifetimes when even a small tensile force is applied to
      the ligand. The discrepancy is so great that it cannot be explained by the
      traditional receptor-ligand binding models. This generic phenomenon is
      rationalized here by considering the interaction of water with the receptor
      ligand complex. It is argued that the water-protein interaction creates an energy
      barrier that prevents the ligand unbinding in the absence of the force. The
      properties of the interaction are such that even application of a relatively low
      force results in a dramatic drop of the bond lifetime due to the alteration of
      the water-receptor and water-ligand interaction network. The phenomenon is
      described by the presence of a second shallow interaction energy minimum for the
      bound ligand followed by a wide receptor-ligand dissociation barrier. The general
      analysis is applied quantitatively to the actin-myosin system, which demonstrates
      the gigantic drop of the bond lifetime at small forces and catch behavior (an
      increase in the lifetime) at moderate forces. The base hypothesis proposed to
      explain the small-force abnormal drop in the bond lifetime suggests that the
      majority of biological bonds may exhibit this phenomenon irrespectively whether
      they behave as slip or catch-slip bonds.

PMID- 18710274
TI  - Temporal metabonomic modeling of l-arginine-induced exocrine pancreatitis.
AB  - The time-related metabolic responses to l-arginine (ARG)-induced exocrine
      pancreatic toxicity were investigated using single ip doses of 1,000 and 4,000
      mg/kg body weight over a 7 day experimental period in male Sprague-Dawley rats.
      Sequential timed urine and plasma samples were analyzed using high resolution
      (1)H NMR spectroscopy together with complementary clinical chemistry and
      histopathology analyses. Principal components analysis (PCA) and orthogonal
      projection on latent structures discriminant analysis (O-PLS-DA) were utilized to
      analyze the (1)H NMR data and to extract and identify candidate biomarkers and to
      construct metabolic trajectories post ARG administration. Low doses of ARG
      resulted in virtually no histopathological damage and distinct reversible
      metabolic response trajectories. High doses of ARG caused pancreatic acinar
      degeneration and necrosis and characteristic metabolic trajectory profiles with
      several distinct phases. The initial trajectory phase (0-8 h) involved changes in
      the urea cycle and transamination indicating a homeostatic response to detoxify
      excess ammonia generated from ARG catabolism. By 48 h, there was a notable
      enhancement of the excretion of the gut microbial metabolites,
      phenylacetylglycine (PAG), 4-cresol-glucuronide and 4-cresol-sulfate, suggesting
      that compromised pancreatic function impacts on the activity of the gut
      microbiota giving potential rise to a novel class of surrogate extragenomic
      biomarkers of pancreatic injury. The implied compromise of microbiotal function
      may also contribute to secondary hepatic and pancreatic toxic responses. We show
      here for the first time the value of metabonomic studies in investigating
      metabolic disruption due to experimental pancreatitis. The variety of observed
      systemic responses suggests that this approach may be of general value in the
      assessment of other animal models or human pancreatitis.

PMID- 18710276
TI  - Lithium calcium imide [Li2Ca(NH)2] for hydrogen storage: structural and
      thermodynamic properties.
AB  - In an attempt to tailor the dehydrogenation temperature of lithium imides, we
      have investigated the ternary imide Li 2Ca(NH) 2, which crystallizes in a
      structure (space group P3 m1) different from that of Li 2Mg(NH) 2 (space group
      Iba2). First-principles density functional calculations yield the stable ground
      state structure along with the correct hydrogen positions. Compared with the
      structural and thermodynamic data of the pure lithium imides, those Ca or Mg
      partially substituted ternary imides show decreased reaction enthalpies as well
      as dehydrogenation temperatures.

PMID- 18710277
TI  - Local control over phase transitions in microgel assemblies.
AB  - Poly( N-isopropylacrylamide) microgels were coassembled with Au nanoparticles
      into disordered glassy phases and irradiated with a tightly focused laser (lambda
      = 532 nm) to study crystallization dynamics following a localized photothermal
      annealing process. The degree of crystallization produced by the annealing
      process is dependent upon heat flux into the sample at the site of irradiation,
      the length of irradiation time, and the temperature of the surrounding bulk
      assembly that functions as a quenching bath. Control over these sample conditions
      provides a method by which to probe the dynamics of crystallization over a set of
      microgel concentrations. The mobility, and thus the crystallization, of particles
      is shown to be frustrated as the microgel concentration is increased. This is in
      contrast with equilibrium experiments that have shown an increase in particle
      mobility with microgel concentration that is manifest as an increase in the
      freezing transition of the bulk assembly with increasing packing density.

PMID- 18710278
TI  - Preparation and characterization of a novel electrospun spider silk
      fibroin/poly(D,L-lactide) composite fiber.
AB  - In the paper, we successfully prepared spider silk fibroins (Ss)/poly( d, l
      lactide) (PDLLA) composite fibrous nonwoven mats for the first time to the best
      of our knowledge. The morphology of the fibers was observed by a scanning
      electron microscope (SEM) and transmission electron microscope (TEM). The
      secondary structure change of the spidroin before and after electrospinning was
      characterized using Fourier transform infrared spectroscopy (FT-IR). Herein, a
      qualitative analysis of the conformational changes of the silk protein was
      performed by analyzing the FT-IR second-derivative spectra, from which
      quantitative information was obtained via the deconvolution of the amide I band.
      A mechanical test was carried out to investigate the tensile strength and the
      elongation at break. A water contact angle (CA) measurement was also performed to
      characterize surface properties of the fibers. The cytotoxicity of electrospun
      PDLLA and Ss-PDLLA nonwoven fibrous mats was evaluated based on a CCL 81(Vero)
      cells proliferation study. The results showed that the hydrophilic and mechanical
      property of the composite fiber were improved by introducing spidroin.

PMID- 18710279
TI  - Alkylamine sensing using langmuir-blodgett films of n-alkyl-N-phenylamide
      substituted zinc porphyrins.
AB  - Two porphyrin compounds, zinc(II) 5,10,15,20-tetrakis(3,5,5-trimethyl- N
      phenylhexanamide)porphyrin and zinc(II) 5,10,15,20-tetrakis(2,2-dimethyl- N
      phenylpropanamide)porphyrin, have been investigated as possible candidates for
      the detection of alkylamines. UV-visible spectroscopy has shown that their
      solution absorption spectra are significantly modified upon interaction with a
      range of organic analytes, including acetic acid, butanone, ethylacetate,
      hexanethiol, octanal, octanol, alkylamines, and trimethylphosphite. Large
      spectral changes are observed for the family of alkylamines as a result of the
      specific affinity between zinc and the amine moiety. Langmuir-Blodgett (LB) films
      of the porphyrins have been fabricated in order to assess their solid-state
      sensing capability toward amines. The surface pressure-area (Pi- A) isotherms
      reveal a clear three-phase Langmuir film behavior and show that these monolayer
      films may be compressed to a relatively high surface pressure ( approximately 40
      50 mN m (-1)). The isotherm data alongside molecular modeling suggest a
      relatively flat orientation of the porphyrin rings of both compounds: that is, a
      mutually parallel alignment of the plane of the porphyrin ring and that of the
      water surface. LB films deposited at 15 mN m (-1) have been exposed to alkylamine
      vapor (carried by N 2). A red shift and increase in intensity of the Soret band
      absorbance is observed which can be reversed by flowing pure N 2 over the gently
      heated sample (60 degrees C) after exposure. Primary amines were expected to
      invoke the greatest sensing response due to (i) their larger association
      constants with these porphyrins compared to secondary and tertiary amines and
      (ii) the ease of diffusion of amines which is expected to follow the order
      primary > secondary > tertiary due to the steric hindrance arising from the bulky
      secondary and tertiary amines. However, the magnitude of the absorbance change is
      largest for exposure to the secondary amines, dipropylamine and dibutylamine, for
      both porphyrins, compared to primary and tertiary amines. This trend follows that
      observed when the amines were added to solutions of the porphyrins. The rate of
      response of the porphyrin LB films falls as the molecular weight of the diffusing
      alkylamine increases. Furthermore, a greater rate of response is observed for the
      phenylhexanamide porphyrin compared to the phenylpropanamide porphyrin due to its
      lower molecular density within the LB film and therefore more porous structure.

PMID- 18710280
TI  - Enhanced hydrophobicity of fluorinated lipid bilayer: a molecular dynamics study.
AB  - A molecular dynamics simulation of a partially fluorinated phospholipid bilayer
      has been carried out to understand the effects of fluorination of the hydrophobic
      chains on the structure and water permeability across the membrane. Fluorocarbon
      chains typically have an all-trans conformation, showing a highly ordered
      structure in the membrane core compared to ordinary hydrocarbon chains. The free
      energy profiles of water across the bilayers were successfully estimated by a
      revised cavity insertion Widom method. The fluorinated bilayer showed a higher
      free energy barrier than an ordinary nonfluorinated lipid bilayer by about 1.2
      kcal/mol, suggesting a lower water permeability of the fluorinated bilayer
      membrane. A cavity distribution analysis elucidated the reduced free volume in
      the fluorinated membrane due to the neatly packed chains, which should account
      for the higher free energy barrier.

PMID- 18710282
TI  - Thiol/acrylate-modified PEO-PPO-PEO triblocks used as reactive and
      thermosensitive copolymers.
AB  - The reactive thermal-sensitive hydrogels, which combined the reversible
      thermosensitive and mild reactive property, were designed based on thiol-ene
      reaction in physiological conditions between thiol and acrylate capped
      thermosensitive Poloxamer 188. The modified P188A, P188SH, and their reactivity
      were characterized by (1)H NMR, FT-IR, GPC, DSC, Ellman method, and Rheometer. It
      was found that the thiol-ene reaction was pH and thermal-sensitive. There was
      77.7% SH involved into the reaction at 37.0 degrees C and pH 7.4 within the first
      30 min. The most of molecules reacted as CC/SH mol ratio was 1.5. The exothermic
      thiol-ene reaction was mild, with about DeltaH = -91.18 J/g changes. The
      multiblocks or network structure limited the dissolution of hydrogel,
      correspondingly the gel's duration and the release time of methylene blue were
      prolonged to 124 h. The experimental results indicated the reactive thermal
      sensitive hydrogel's potential applications in drug delivery, tissue engineering,
      and cell encapsulation.

PMID- 18710284
TI  - Evolving trends in the dereplication of natural product extracts: new methodology
      for rapid, small-scale investigation of natural product extracts.
AB  - The use of an HPLC bioactivity profiling/microtiter plate technique in
      conjunction with capillary probe NMR instrumentation and access to appropriate
      databases effectively short-circuits conventional dereplication procedures,
      necessarily based on multimilligram extracts, to a single, more rapid
      submilligram operation. This approach to dereplication is illustrated using
      fungal or bacterial extracts that contain known compounds. In each case the
      dereplication steps were carried out on microgram quantities of extract and
      demonstrate the discriminating power of (1)H NMR spectroscopy as a definitive
      dereplication tool.

PMID- 18710283
TI  - Tetrahdroxysqualene from Rhus taitensis shows antimycobacterial activity against
      Mycobacterium tuberculosis.
AB  - Tuberculosis has become a major health problem, in particular with the emergence
      of extremely drug resistant tuberculosis (XDRTB). In our search for new
      therapeutic leads against TB, we isolated a new triterpene (1) from the plant
      Rhus taitensis collected in Papua New Guinea. Tetrahydroxysqualene (1) was
      isolated using bioassay-guided fractionation of the methanolic extract of R.
      taitensis leaves and twigs. The structure of tetrahydroxysqualene (1) was
      elucidated on the basis of HRESIMS and 1D and 2D NMR spectra.
      Tetrahydroxysqualene (1) exhibited antituberculosis activity with an MIC of 10.0
      microg/mL, while showing only modest cytotoxicity.

PMID- 18710285
TI  - Cobalt-catalyzed asymmetric olefin aziridination with diphenylphosphoryl azide.
AB  - The cobalt(II) complexes of D2-symmetric chiral porphyrins, such as 3,5-Di(t)Bu
      ChenPhyrin P5, can catalyze asymmetric olefin aziridination with
      diphenylphosphoryl azide (DPPA) as a nitrene source. Acceptable asymmetric
      inductions were observed for the [Co(P5)]-based catalytic system, forming the
      desired N-phosphorus-substituted aziridines in moderate to high yields and good
      enantioselectivities.

PMID- 18710286
TI  - Matrix isolation and EPR spectroscopy of septet 3,5-difluoropyridyl-2,4,6
      trinitrene.
AB  - Septet 3,5-difluoropyridyl-2,4,6-trinitrene along with quintet 2-azido-3,5
      difluoropyridyl-4,6-dinitrene, quintet 4-azido-3,5-difluoropyridyl-2,6-dinitrene,
      triplet 2,6-diazido-3,5-difluoropyridyl-4-nitrene, and triplet 2,4-diazido-3,5
      difluoropyridyl-6-nitrene have been obtained by photolysis of 2,4,6-triazido-3,5
      difluoropyridine in solid argon at 4 K. The electronic and magnetic properties of
      the matrix-isolated nitrenes were studied using electron paramagnetic resonance
      (EPR) spectroscopy in combination with density functional theory (DFT)
      calculations. The fine-structure parameters of the nitrenes were determined with
      high accuracy from computer spectral simulations. All signals in the EPR spectra
      of the nitrenes randomly oriented in the solid phase were unambiguously assigned
      on the basis of eigenfield calculations of the Zeeman energy levels and angular
      dependencies of resonance fields from the direction of the applied magnetic
      field.

PMID- 18710287
TI  - Efficient access to 2-isobetulinic acid, 2-isooleanolic acid, and 2-isoursolic
      acid.
AB  - An efficient access to 2-isobetulin, 2-isobetulinic acid, 2-isooleanolic acid,
      and 2-isoursolic acid has been developed. The key step is a novel one-pot
      conversion of 2,3-dihydroxy triterpenes to 3-deoxy-2-oxo triterpenes. This method
      provides a new access to 3-deoxy-2-substituted pentacyclic triterpenes as
      potential therapeutic agents against metabolic diseases, tumors, and HIV
      infection.

PMID- 18710288
TI  - Unexpected solvent-free cycloadditions of 1,3-cyclohexanediones to 1-(pyridin-2
      yl)-enones mediated by manganese(III) acetate in a ball mill.
AB  - Under solvent-free ball-milling conditions, manganese(III) acetate dihydrate
      mediated cycloadditions of 5,5-dimethyl-1,3-cyclohexanedione and 1,3
      cyclohexanedione to various 1-(pyridin-2-yl)-enones proceeded efficiently to
      afford trans-2-acyl-3-aryl/alkyl-2,3,6,7-tetrahydro-4(5H)-benzofuranone
      derivatives. The cyclization reactions exhibited good to excellent yields, as
      well as extremely high diastereoselectivity and unexpected regioselectivity.
      Manganese(III) acetate behaved both as an oxidant and as a Lewis acid.

PMID- 18710289
TI  - Nucleic acid structural engineering using pyrene-functionalized 2'-amino-alpha-L
      LNA monomers and abasic sites.
AB  - Oligonucleotides (ONs) modified with a 2'-N-(pyren-1-yl)acetyl-2'-amino-alpha-L
      LNA thymine monomer Y flanked on the 3'-side by an abasic site Phi (i.e., YPhi
      unit) exhibit unprecedented increases in thermal affinity (DeltaT(m) values)
      toward target strands containing abasic sites (DeltaT(m) per YPhi unit >+33.0
      degrees C in 9-mer duplexes relative to unmodified ONs). Biophysical studies
      along with force field calculations suggest that the conformationally locked 2
      oxo-5-azabicyclo[2.2.1]heptane skeleton of monomer Y, in concert with the short
      rigid acetyl linker, efficiently forces the thymine and pyrene moieties to adopt
      an interplanar distance of approximately 3.4 A. This precisely positions the
      pyrene moiety in the duplex core void formed by abasic sites (Phi:Phi pair) for
      optimal pi-pi overlap. Duplexes with multiple YPhi: APhi units separated by one
      base pair are tolerated extraordinarily well, as exemplified by a 13-mer duplex
      containing four separated YPhi: APhi units (8 abasic sites distributed over 13
      "base pairs"), which exhibit a thermal denaturation temperature of 60.5 degrees
      C. The YPhi probes display up to 16-fold increases in fluorescence intensity at
      380 nm upon hybridization with abasic target strands, whereby self-assembly of
      these complex architectures can be easily monitored. This study underlines the
      potential of N2'-functionalized 2'-amino-alpha-L-LNA as building blocks in
      nucleic acid based diagnostics and nanomaterial engineering.

PMID- 18710290
TI  - Synthesis and an evaluation of the bioactivity of the C-glycoside of
      pseudopterosin A methyl ether.
AB  - The Suzuki-Miyaura cross-coupling protocol was applied to the synthesis of 1a,
      the C-glycoside analogue of PsA methyl ether. This marks the first construction
      of a C-glycoside for this class of marine natural products, thereby offering an
      opportunity to compare its bioactivity to the natural substances. Its activity
      profile resembled that of PsA (1) and PsA O-methyl ether (1b) when assayed for
      its anti-inflammatory activity and its ability to inhibit phagocytosis. We
      conclude that the intact structure is present when a pseudopterosin expresses its
      anti-inflammatory and phagocytosis inhibitory properties and that they are,
      therefore, not likely to be prodrugs. Results show that 1a is an effective
      binding agent toward the A2A and A3 adenosine receptors, displaying IC50 values
      of 20 and 10 microM, respectively.

PMID- 18710291
TI  - Cyclobutanone mimics of penicillins: effects of substitution on conformation and
      hemiketal stability.
AB  - The tendency for carbocyclic analogues of penicillins to undergo hydrate and
      hemiketal formation is central to their ability to function as beta-lactamase
      inhibitors. 2-Thiabicyclo[3.2.0]heptan-6-one-4-carboxylates with alkoxy
      functionality at C3 have been prepared through two complementary
      diastereoselective substitution reactions following a highly stereoselective
      chlorination with sulfuryl chloride. We have found that carbocyclic analogues
      with 3beta substituents favor an endo envelope conformation in solution, the
      solid state, and the gas phase, whereas those with 3alpha substituents adopt an
      exo envelope. Evidence from X-ray crystal structures and ab initio calculations
      suggests that an anomeric effect contributes to the large conformational
      preference of the tetrahydrothiophene ring that favors the C3 substituent in an
      axial orientation. In addition, the envelope conformation of the bicycle, which
      is determined by the stereochemistry of the C3 substituent, has a dramatic effect
      on the ability of the cyclobutanone to undergo hemiketal formation in methanol
      d4.

PMID- 18710292
TI  - Intimate molecular interactions of P. falciparum merozoite proteins involved in
      invasion of red blood cells and their implications for vaccine design.

PMID- 18710294
TI  - Controlled synthesis of millimeter-long silicon nanowires with uniform electronic
      properties.
AB  - We report the nanocluster-catalyzed growth of ultralong and highly uniform single
      crystalline silicon nanowires (SiNWs) with millimeter-scale lengths and aspect
      ratios up to approximately 100,000. The average SiNW growth rate using disilane
      (Si 2H 6) at 400 degrees C was 31 microm/min, while the growth rate determined
      for silane (SiH 4) reactant under similar growth conditions was 130 times lower.
      Transmission electron microscopy studies of millimeter-long SiNWs with diameters
      of 20-80 nm show that the nanowires grow preferentially along the 110 direction
      independent of diameter. In addition, ultralong SiNWs were used as building
      blocks to fabricate one-dimensional arrays of field-effect transistors (FETs)
      consisting of approximately 100 independent devices per nanowire. Significantly,
      electrical transport measurements demonstrated that the millimeter-long SiNWs had
      uniform electrical properties along the entire length of wires, and each device
      can behave as a reliable FET with an on-state current, threshold voltage, and
      transconductance values (average +/-1 standard deviation) of 1.8 +/- 0.3 microA,
      6.0 +/- 1.1 V, 210 +/- 60 nS, respectively. Electronically uniform millimeter
      long SiNWs were also functionalized with monoclonal antibody receptors and used
      to demonstrate multiplexed detection of cancer marker proteins with a single
      nanowire. The synthesis of structurally and electronically uniform ultralong
      SiNWs may open up new opportunities for integrated nanoelectronics and could
      serve as unique building blocks linking integrated structures from the nanometer
      through millimeter length scales.

PMID- 18710293
TI  - High throughput synthesis of peptide alpha-thioesters through the use of
      "volatilizable" support.

PMID- 18710295
TI  - Au stabilization and coverage of sawtooth facets on Si nanowires grown by vapor
      liquid-solid epitaxy.
AB  - Si nanowires grown in UHV by Au-catalyzed vapor-liquid-solid epitaxy are known to
      exhibit sidewalls with {112}-type orientation that show faceting. To understand
      the origin of the faceting, Au induced faceting on Si(112) surfaces was studied
      in situ by spot-profile-analyzing low-energy electron diffraction. With
      increasing Au coverage at 750 degrees C, the Si(112) surface undergoes various
      morphological transformations until, at a critical Au coverage of about 3.1 x 10
      (14) atoms/cm (2), a phase consisting of large (111) and (113) facets forms,
      similar in structure to the nanowire sidewalls. This phase is stable at larger Au
      coverages in equilibrium with Au droplets. We suggest that Si nanowire surfaces
      exhibit this structure, and we derive the Au coverage on the two types of facets.

PMID- 18710296
TI  - Metallic nanohole arrays on fluoropolymer substrates as small label-free real
      time bioprobes.
AB  - We describe a nanoplasmonic probing platform that exploits small-dimension
      (<or=20 microm (2)) ordered arrays of subwavelength holes for multiplexed, high
      spatial resolution, and real-time analysis on biorecognition events. Nanohole
      arrays are perforated on a super smooth gold surface (roughness rms < 2.7 A)
      attached on a fluoropolymer (FEP) substrate fabricated by a replica technique.
      The smooth surface of gold provides a superb environment for fabricating
      nanometer features and uniform immobilization of biomolecules. The refractive
      index matching between FEP and biological solutions contributes to approximately
      20% improvement on the sensing performance. Spectral studies on a series of small
      dimension nanohole arrays from 1 microm (2) to 20 microm (2) indicate that the
      plasmonic sensing sensitivity improves as the gold-solution contact area
      increases. Our results also demonstrate that nanohole arrays with a dimension as
      small as 1 microm (2) can be used to effectively detect biomolecular binding
      events and analyze the binding kinetics. The future scientific opportunities
      opened by this nanohole platform include highly multiplexed analysis of ligand
      interactions with membrane proteins on high quality supported lipid bilayers.

PMID- 18710297
TI  - Negative differential resistance in carbon atomic wire-carbon nanotube junctions.
AB  - Negative differential resistance (NDR) was recently observed in carbon nanotube
      junctions just before breaking and hypothesized to arise from the formation of
      monatomic carbon wires in the junction. Motivated by these results, a first
      principles scattering-state approach, based on density functional theory, is used
      to study the transport properties of carbon chains covalently connecting metallic
      carbon nanotube leads at finite bias. The I- V characteristics of short carbon
      chains are predicted to exhibit even-odd behavior, and NDR is found for both even
      and odd chain junctions in our calculations.

PMID- 18710298
TI  - Identification and description of Bucephalus minimus (Digenea: Bucephalidae) life
      cycle in Portugal: morphological, histopathological, and molecular data.
AB  - The cercaria of Bucephalus minimus infects the digestive gland and gonads of its
      first intermediate host, the edible cockle, Cerastoderma edule. Light microscopy
      (LM) and scanning electron microscopy (SEM) of the cercaria showed a tail formed
      by a central stem, with 2 long contractile arms presenting distinct morphological
      surfaces. The encysted metacercaria naturally infected the flathead grey mullet,
      Mugil cephalus. The cysts found in the heart, liver, and spleen were shown to be
      identical by the internal transcribed spacer (ITS 1) sequence and morphological
      features and were associated with encapsulation, recruitment of cell infiltrates,
      and presence of melanomacrophages and adipose tissue. To establish the life
      cycle, we compared the ITS1 sequence in an adult from the known definitive host,
      Dicentrarchus labrax; encysted metacercariae from the liver, heart, and spleen of
      M. cephalus; and a cercaria from C. edule. With this comparison, we determined
      that they had a 100% similarity. Therefore, the ITSI sequence data clearly
      indicate that these 3 parasitic stages belong to the same species, i.e., B.
      minimus.

PMID- 18710299
TI  - Molecular and morphological description of a Hepatozoon species in reptiles and
      their ticks in the Northern Territory, Australia.
AB  - Ticks, representing 3 species of Amblyomma, were collected from the water python
      (Liasis fuscus) and 3 additional reptile species in the Northern Territory,
      Australia, and tested for the presence of Hepatozoon sp., the most common blood
      parasites of snakes. In addition, blood smears were collected from 5 reptiles,
      including the water python, and examined for the presence of the parasite.
      Hepatozoon sp. DNA was detected in all tick and reptile species, with 57.7% of
      tick samples (n = 187) and 35.6% of blood smears (n=35) showing evidence of
      infection. Phylogenetic analysis of the 18S rRNA gene demonstrated that half of
      the sequences obtained from positive tick samples matched closest with a
      Hepatozoon species previously identified in the water python population. The
      remaining sequences were found to be more closely related to mammalian and
      amphibian Hepatozoon species. This study confirms that species of Amblyomma
      harbor DNA of the same Hepatozoon species detected in the water pythons. The
      detection of an additional genotype suggests the ticks may be exposed to 2
      Hepatozoon species, providing further opportunity to study multiple host-vector
      parasite relationships.

PMID- 18710300
TI  - Effects of dietborne copper and silver on reproduction by Ceriodaphnia dubia.
AB  - Recent studies have indicated the potential for dietborne metals as an important
      exposure pathway for metal toxicity in freshwater organisms. We conducted a study
      in which freshwater cladocerans (Ceriodaphnia dubia) were fed green algae (either
      Pseudokirchneriella subcapitata or Chlorella vulgaris) that were grown in Ag- or
      Cu-contaminated media. In one series of toxicity tests patterned after the U.S.
      Environmental Protection Agency's three-brood C. dubia chronic toxicity test, we
      exposed C. dubia to waterborne Ag or Cu while feeding them normal amounts of
      uncontaminated yeast-Cerophyll-trout chow (YCT) slurry and either algae grown in
      standard media or algae grown in standard media supplemented with Ag or Cu (added
      as AgNO3 or CuSO4 x 5H2O). These parallel tests demonstrated that dietborne metal
      did not contribute to survival or reproduction effects beyond the effects caused
      by waterborne metal alone. We also conducted dietborne-only toxicity tests
      patterned after two other recently published experimental designs in which (1) C.
      dubia were fed only metal-contaminated algae for 4 h, transferred to fresh water,
      and fed uncontaminated algae and YCT slurry for the duration of the three-brood
      test or (2) C. dubia were fed standard amounts of metal-contaminated algae and
      uncontaminated YCT slurry for the entire three-brood test. In contrast to
      previous studies, we did not find consistent dietborne metal toxicity or standard
      concentration-response relationships in those two experiments. Instead, among
      experiment variation in intracellular partitioning of metals in the algae fed to
      the C. dubia, among-laboratory differences in experimental procedures, selective
      feeding by C. dubia to avoid metal-contaminated algae, an interaction between
      reproductive status of the C. dubia and dietborne metal concentration, or a
      combination of these might help explain the apparently inconsistent results.

PMID- 18710301
TI  - Effect of triclosan on microbial activity in Australian soils.
AB  - Triclosan (TCS) antimicrobial compound is used in personal care products such as
      shampoos and soaps. The TCS compound can survive the treatment process and is
      often present in the sewage effluent and biosolids. We investigated the impact of
      TCS upon selected microbiological and biochemical parameters in two contrasting
      Australian soils. Substrate-induced respiration and nitrification, plus
      activities of four enzymes (relevant for carbon and nitrogen turnover), were
      measured using Organisation for Economic Co-operation and Development protocols
      after exposing soils to TCS at concentrations of 0, 1, 5, 10, 50, and 100 mg/kg
      of soil. Respiration in the sandy soil was not affected by the addition of TCS,
      but in clay soil it decreased to TCS at 50 mg/kg of soil. The nitrification
      process was affected in both soils. In the sandy soil, TCS showed a negative
      effect on the nitrate and nitrite production at 5 mg/kg. In contrast, in the clay
      soil, the effect was noticeable only at concentrations greater than 50 mg/kg. The
      response of four enzymes (acid and alkali phosphatase, 3-glucosidase, and
      chitinase) in the two soils was variable, and only P3-glucosidase showed some
      response to TCS addition. The study demonstrated that TCS at concentrations below
      10 mg/kg can disturb the nitrogen cycle in some soils. A first-tier hazard
      assessment highlighted the need for further work on TCS impact on soil
      microorganisms.

PMID- 18710303
TI  - Determination of the cleavage plane in early C. elegans embryos.
AB  - Cells split in two at the final step of each division cycle. This division
      normally bisects through the middle of the cell and generates two equal
      daughters. However, developmental signals can change the plane of cell cleavage
      to facilitate asymmetric segregation of fate determinants and control the
      position and relative sizes of daughter cells. The anaphase spindle instructs the
      site of cell cleavage in animal cells, hence its position is critical in the
      regulation of symmetric vs asymmetric cell division. Studies in a variety of
      models identified evolutionarily conserved mechanisms that control spindle
      positioning. However, how the spindle determines the cleavage site is poorly
      understood. Recent results in Caenorhabditis elegans indicate dual functions for
      a Galpha pathway in positioning the spindle and cleavage furrow. We review
      asymmetric division of the C. elegans zygote, with a focus on microtubule-cortex
      interactions that position the spindle and cleavage plane.

PMID- 18710304
TI  - Roles of thermal adaptation and chemical ecology in Liriomyza distribution and
      control.
AB  - Many Liriomyza species are pests of agricultural and ornamental plants. In the
      past two decades, the occurrence and distribution of certain Liriomyza species
      have changed dramatically, leading to an extensive body of research papers.
      First, we review the association of thermal tolerance with population dynamics,
      geographic distribution, and species displacement. Differences in thermal
      tolerances between species result in their differential geographic locations and
      overwintering ranges. Displacements among Liriomyza species are associated with
      their temperature adaptation. We examine the chemical linkage of plants,
      Liriomyza, and their parasitoids. Chemical compounds from host and nonhost plants
      mediate the behavior of Liriomyza and their parasitoids. Liriomyza and their
      parasitoids use chemical cues to locate their hosts. Induced compounds can be
      used as attractants of parasitoids or repellents of Liriomyza. Thus,
      understanding the thermal tolerances and chemical ecology of Liriomyza may enable
      researchers to predict geographic distribution and to develop novel control
      strategies.

PMID- 18710302
TI  - Planar cell polarity signaling: from fly development to human disease.
AB  - Most, if not all, cell types and tissues display several aspects of polarization.
      In addition to the ubiquitous epithelial cell polarity along the apical
      basolateral axis, many epithelial tissues and organs are also polarized within
      the plane of the epithelium. This is generally referred to as planar cell
      polarity (PCP; or historically, tissue polarity). Genetic screens in Drosophila
      pioneered the discovery of core PCP factors, and subsequent work in vertebrates
      has established that the respective pathways are evolutionarily conserved. PCP is
      not restricted only to epithelial tissues but is also found in mesenchymal cells,
      where it can regulate cell migration and cell intercalation. Moreover,
      particularly in vertebrates, the conserved core PCP signaling factors have
      recently been found to be associated with the orientation or formation of cilia.
      This review discusses new developments in the molecular understanding of PCP
      establishment in Drosophila and vertebrates; these developments are integrated
      with new evidence that links PCP signaling to human disease.

PMID- 18710306
TI  - Veterinarians keep an eye on the economy.

PMID- 18710307
TI  - Thoughts on AVMA policy on elephant guides and tethers.

PMID- 18710308
TI  - What is your diagnosis? Abdominal hernia and hepatomegaly.

PMID- 18710309
TI  - ECG of the Month. Atrial premature complex.

PMID- 18710310
TI  - Issues regarding the use of vancomycin in companion animals.

PMID- 18710311
TI  - Glanders.

PMID- 18710312
TI  - Analysis of auditory and neurologic effects associated with ventral bulla
      osteotomy for removal of inflammatory polyps or nasopharyngeal masses in cats.
AB  - OBJECTIVE: To determine whether cats undergoing ventral bulla osteotomy (VBO) for
      removal of inflammatory polyps or nasopharyngeal masses have altered ability to
      hear and whether polyp or mass removal affects auditory function as measured via
      air-conducted brainstem auditory evoked response (BAER). DESIGN: Prospective case
      series. ANIMALS: 21 cats. PROCEDURES: Cats were sedated and had otic-oral
      examinations to confirm presence of nasopharyngeal masses; BAER testing was done
      immediately prior to and following the completion of a VBO and polyp or mass
      removal. Recheck examination, including otic examination and BAER in sedated
      cats, was performed when possible. Results-17 cats met final inclusion criteria,
      and long-term follow-up was available for 15. Six of 17 had deafness as measured
      via air-conducted BAER prior to surgery. Mean followup time was 161 days, and
      there was no change from presurgical status in auditory ability in any cat.
      Eleven of 17 developed ipsilateral Horner syndrome in the immediate postoperative
      period, and 1 of 16 had polyp regrowth. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggested that in cats, VBO for removal of inflammatory polyps or masses
      is unlikely to affect hearing as measured via air-conducted BAER. Most cats
      developed short-term Horner syndrome. Cats with deafness prior to surgery did not
      regain auditory function. Ventral bulla osteotomy to remove nasopharyngeal polyps
      or masses provided no functional advantage with regard to restoration of hearing,
      compared with other surgical techniques. Polyp recurrence and long-term adverse
      effects were uncommon.

PMID- 18710313
TI  - Evaluation of inciting causes, alternative targets, and risk factors associated
      with redirected aggression in cats.
AB  - OBJECTIVE: To identify inciting causes, alternative targets, and risk factors
      associated with redirected aggression in cats. DESIGN: Case-control study.
      ANIMALS: 19 cats with a history of redirected aggression and 64 cats with no such
      history. PROCEDURES: Medical records were reviewed to identify cats evaluated for
      problems with redirected aggression (case cats), in which the primary inciting
      stimulus and alternative target of aggression were clearly identifiable. Data
      obtained from the records and from follow-up interviews included details about
      the cats and incidents of redirected aggression. Owners of control cats were
      interviewed via telephone to obtain similar information on their cats. RESULTS:
      22 incidents of redirected aggression were reported for the 19 case cats. In 95%
      of those incidents, loud noises or interactions with other cats were identified
      as the inciting stimuli. Case cats most commonly redirected their aggression
      toward the owner, followed by another cat living in the same household. Compared
      with control cats, case cats were more likely to have a sound phobia but were
      less likely to be outdoor cats. In addition, case cats were more likely to be
      from small households (<or= 2 people) than were control cats. In most situations,
      case cats had adopted a defensive body posture immediately before the incident of
      redirected aggression, which suggested that the underlying motivation was fear.
      CONCLUSIONS AND CLINICAL RELEVANCE: Fear was likely the most common motivation
      for redirected aggression in the cats of this report. To reduce the risk of
      redirected aggression, veterinarians should encourage owners to socialize kittens
      and habituate them to novel objects and sounds.

PMID- 18710314
TI  - Ultrasonographic appearance of the coelomic cavity in healthy green iguanas.
AB  - OBJECTIVE: To describe the ultrasonographic appearance of the coelomic cavity in
      healthy green iguanas. DESIGN: Cross-sectional study. ANIMALS: 26 healthy green
      iguanas (20 males and 6 females). PROCEDURES: For coelomic ultrasonography,
      animals were physically restrained in dorsal recumbency by an assistant; chemical
      restraint was not used. Qualitative and quantitative observations were recorded.
      RESULTS: Structures that could be visualized in all animals included the heart
      and cardiac chambers; liver; caudal vena cava; hepatic veins; portal vein;
      gallbladder; pyloric portion of the stomach; and, when distended, urinary
      bladder. Visualization of the kidneys was poor. The spleen could be identified in
      17 animals, and the gonads could be identified in 22, but were most easily
      identified in males evaluated during November (ie, during the breeding season);
      no females were evaluated during the breeding season. Physiologic enlargement of
      the testes yielded an acoustic window for the spleen by displacing overlying
      intestine. Anechoic, free coelomic fluid was identified in 3 animals.
      Measurements of overall cardiac size, ventricular wall thickness, gallbladder
      size, thickness of the pyloric portion of the stomach, and splenic size were
      obtained. Only ventricular wall thickness was significantly correlated with body
      weight. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that
      ultrasonography allowed examination of most coelomic structures in green iguanas.
      The procedure was easily performed and was well tolerated in conscious animals.

PMID- 18710315
TI  - Failure to identify an association between serologic or molecular evidence of
      Bartonella infection and idiopathic rhinitis in dogs.
AB  - OBJECTIVE: To determine whether infection with or exposure to Bartonella spp was
      associated with idiopathic rhinitis in dogs. DESIGN: Case-control study. ANIMALS:
      44 dogs with idiopathic nasal discharge and 63 age- and weight-matched control
      dogs without nasal discharge and no clinical signs of bartonellosis. Procedures
      Serum was tested for antibodies against Bartonella henselae and Bartonella
      vinsonii subsp berkhoffii with indirect fluorescent antibody assays. Blood was
      tested for Bartonella DNA with a PCR assay. RESULTS: Results of the antibody and
      PCR assays were negative for all 44 dogs with idiopathic nasal discharge. One
      control dog had antibodies against B henselae; a second control dog had positive
      PCR assay results. We did not detect a significant association between assay
      results and group designation. CONCLUSIONS AND CLINICAL RELEVANCE: The present
      study failed to confirm an association between idiopathic rhinitis and exposure
      to or infection with Bartonella spp in dogs. Findings do not rule out the
      possibility that Bartonella infection may cause nasal discharge in some dogs, but
      the failure to find any evidence of exposure to or infection with Bartonella spp
      in dogs with idiopathic nasal discharge suggested that Bartonella infection was
      not a common cause of the disease.

PMID- 18710316
TI  - Clinical, radiographic, and pathologic abnormalities in dogs with multiple
      epiphyseal dysplasia: 19 cases (1991-2005).
AB  - OBJECTIVE: To determine clinical, radiographic, and pathologic abnormalities in
      dogs with multiple epiphyseal dysplasia (MED). DESIGN: Retrospective case series.
      ANIMALS: 19 dogs with MED from 10 litters. PROCEDURES: The diagnosis was made on
      the basis of radiographs of the shoulder region and vertebral column. Ten dogs
      underwent necropsy. RESULTS: There were 11 Hygenhund, 6 Dunker, 1 Golden
      Retriever, and 1 English Pointer. Most dogs were examined because of lameness
      that developed at 5 to 8 months of age. The most common radiographic abnormality
      was a deficiency in ossification of the epiphyses, apophyses, and cuboidal bones
      of the appendicular skeleton and the epiphyses of the vertebrae; ossification of
      the metaphyses and the diaphyses typically were normal. Disease severity was
      consistent among littermates, but varied among dogs from different litters.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that MED is a rare
      condition in dogs characterized by a deficiency in ossification of the epiphyses
      of the long bones, the epiphyses of the vertebrae, the cuboidal bones, and the
      apophyses. Radiographic abnormalities were evident in dogs examined as young as 8
      weeks of age, and most dogs had developed severe lameness by 5 to 8 months of
      age. The condition most likely had an autosomal recessive mode of inheritance,
      although genetic studies of mode of inheritance could not be performed.

PMID- 18710318
TI  - Evaluation of use of human albumin in critically ill dogs: 73 cases (2003-2006).
AB  - OBJECTIVES: To evaluate the use of human albumin in critically ill dogs. Design
      Retrospective case series. ANIMALS: 73 client-owned hospitalized dogs.
      PROCEDURES: Medical records of dogs that received human albumin were reviewed to
      assess effects of the use of human albumin on serum albumin concentration,
      colloid osmotic pressure, and total protein concentration; determine the
      relationships between these variables and outcome; and assess its safety. Data
      for signalment, diagnoses, physiologic variables, dosage, amount of crystalloid
      fluid administered prior to human albumin administration, complications, and
      outcome were reviewed. Additionally, pre- and postadministration values for serum
      albumin, colloid osmotic pressure, and total protein were recorded. RESULTS:
      Administration of human albumin resulted in significant changes in serum albumin,
      colloid osmotic pressure, and total protein. The serum albumin, total protein,
      degree of improvement in serum albumin, colloid osmotic pressure, and dosage of
      human albumin were significantly greater in survivors. Seventeen of 73 (23%) dogs
      had at least 1 complication that could be potentially associated with the
      administration of human albumin that occurred during or immediately following
      administration of human albumin. Three of 73 (4%) dogs had severe delayed
      complications. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of human
      albumin significantly increased serum albumin, and total protein concentrations
      and colloid osmotic pressure, especially in survivors. Because of the high
      mortality rate of the study population and other confounding factors, it was
      uncertain whether complications were associated with the underlying disease or
      with human albumin administration. Acute and delayed complications may have been
      under-recognized.

PMID- 18710319
TI  - Comparison of temperature readings from a percutaneous thermal sensing microchip
      with temperature readings from a digital rectal thermometer in equids.
AB  - OBJECTIVE: To compare temperature readings from an implantable percutaneous
      thermal sensing microchip with temperature readings from a digital rectal
      thermometer, to identify factors that affect microchip readings, and to estimate
      the sensitivity and specificity of the microchip for fever detection. DESIGN:
      Prospective study. ANIMALS: 52 Welsh pony foals that were 6 to 10 months old and
      30 Quarter Horses that were 2 years old. PROCEDURES: Data were collected in
      summer, winter, and fall in groups 1 (n = 23 ponies), 2 (29 ponies), and 3 (30
      Quarter Horses), respectively. Temperature readings from a digital rectal
      thermometer and a percutaneous thermal sensing microchip as well as ambient
      temperature were recorded daily for 17, 23, and 19 days in groups 1 through 3,
      respectively. Effects of ambient temperature and rectal temperature on thermal
      sensor readings were estimated. Sensitivity and specificity of the thermal sensor
      for detection of fever (rectal temperature, >or= 38.9 degrees C [102 degrees F])
      were estimated separately for data collection at ambient temperatures <or= 15.6
      degrees C (60 degrees F) and > 15.6 degrees C. RESULTS: Mean ambient temperatures
      were 29.0 degrees C (84.2 degrees F), -2.7 degrees C (27.1 degrees F), and 10.4
      degrees C (50.8 degrees F) for groups 1 through 3, respectively. Thermal sensor
      readings varied with ambient temperature and rectal temperature. Rectal
      temperatures ranged from 36.2 degrees to 41.7 degrees C (97.2 degrees to 107
      degrees F), whereas thermal sensor temperature readings ranged from 23.9 degrees
      (75 degrees F) to 42.2 degrees C (75 degrees to 108 degrees F). Sensitivity for
      fever detection was 87.4%, 53.3%, and 58.3% in groups 1 to 3, respectively.
      CONCLUSIONS AND CLINICAL RELEVANCE: The thermal sensor appeared to have potential
      use for initial screening of body temperature in equids at ambient temperatures >
      15.6 degrees C.

PMID- 18710321
TI  - Outbreak of Salmonella enterica serotype Newport in a beef cow-calf herd
      associated with exposure to bovine viral diarrhea virus.
AB  - CASE DESCRIPTION: Severe disease and death in cows and calves affected 1 of 3
      separate groups (A, B, and C) of cattle on a commercial cow-calf operation.
      CLINICAL FINDINGS: Clinical illness consisting of severe watery and bloody
      diarrhea, dehydration, weakness, and death affected adult cows and calves in 1
      group (group B). Salmonella enterica serotype Newport was recovered from tissues
      of cows and calves from group B. TREATMENT AND OUTCOME: Despite supportive and
      antimicrobial treatment of cattle in group B, cow mortality rate attributable to
      salmonellosis in that group was 7.9% (32/407); calf mortality rate was 14.4%
      (52/361). None of the cows in Groups A or C died, and the calf mortality rate in
      those groups was low. Salmonella enterica serotype Newport was recovered from
      pooled fecal samples subsequently collected from each group of cows. Bovine viral
      diarrhea virus (BVDV) antigen was identified in an ear notch sample collected
      from a necropsied calf from group B. Subsequently, ear notch specimens from
      cattle in all 3 groups were tested for BVDV antigen. A significantly higher
      proportion of calves persistently infected with BVDV was identified in group B
      (8/295 [2.7%]), compared with the proportion in groups A and C combined (1/287
      [0.3%]). CLINICAL RELEVANCE: Outbreaks of disease attributable to Salmonella
      Newport infection in beef cattle are unusual. Because of the immunosuppressive
      nature of BVDV, the possibility of animals persistently infected with BVDV within
      the herd should be considered during investigation of unusual outbreaks of
      infectious diseases.

PMID- 18710323
TI  - Triglycerides potentiate the inflammatory response in rat Kupffer cells.
AB  - Accumulation of fat in the liver, also known as steatosis, may lead to
      inflammation and tissue damage. Kupffer cells (KCs) are the resident macrophages
      of the liver and have an important role in inflammatory reactions. The
      inflammatory response of isolated rat KCs to endotoxin in the presence of lipids
      was investigated in this study. KCs were treated with lipopolysaccharide (LPS)
      and triglycerides (TGs) alone or in combination. TGs had no effect on the
      expression of pro-inflammatory mediators, but adding TGs to LPS enhanced the
      induction of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and granulocyte
      colony-stimulating factor (G-CSF), compared with LPS treatment alone. Increased
      DNA binding of NF-kappaB transcription factor was seen on simultaneous exposure
      of the cells to TGs and LPS, which was accompanied by decreased intracellular ROS
      production and increased GSH levels. The inflammation-potentiating effect of TGs
      on iNOS expression was abolished on NF-kappaB inhibition. This enhanced
      inflammatory response might indicate a contribution of lipids to the inflammatory
      conditions in the fatty liver by increased activation of KCs.

PMID- 18710324
TI  - Initial and subsequent response to pneumococcal polysaccharide and protein
      conjugate vaccines administered sequentially to adults who have recovered from
      pneumococcal pneumonia.
AB  - BACKGROUND: Controversy persists over the benefits of pneumococcal polysaccharide
      vaccine (PPV) for adults at high risk for pneumococcal disease. We studied PPV,
      protein-conjugate pneumococcal vaccine (PCV), and immunologic "priming" with PCV
      followed by "boosting" with PPV in adults who had recovered from pneumococcal
      pneumonia. METHODS: Subjects received PPV followed by PCV 6 months later, or vice
      versa. The levels of IgG to capsular polysaccharide and opsonophagocytic killing
      activity (OPK) were studied at baseline and at 4-8 weeks and 6 months after each
      vaccination. RESULTS: PPV and PCV stimulated similar IgG levels and OPK at 4-8
      weeks after vaccination. Six months after receipt of PPV, the antibody levels
      declined to baseline but remained modestly elevated after receipt of PCV. PCV
      administered 6 months after PPV stimulated modest increases in IgG level that
      failed to reach the peaks observed after receipt of PPV. In contrast, PPV
      administered 6 months after PCV caused dramatic increases in the levels of IgG
      and OPK for all polysaccharides at 4-8 weeks, consistent with a booster effect.
      Six months after receipt of the second vaccination, however, levels of IgG and
      OPK fell precipitously in all patients, approaching baseline levels. CONCLUSIONS:
      In these high-risk subjects who have recovered after treatment for pneumonia, the
      effect of PPV is short-lived; PCV stimulates a more prolonged response. The use
      of PPV as a booster following PCV causes early increases in antibody levels, but
      the level of IgG declines rapidly thereafter, consistent with induction of
      suppressor cells or tolerance. Protein vaccines may be needed for high-risk
      adults.

PMID- 18710325
TI  - Acute chemokine response in the blood and cerebrospinal fluid of children with
      enterovirus 71-associated brainstem encephalitis.
AB  - BACKGROUND: Brainstem encephalitis (BE) is a serious neurological complication of
      enterovirus 71 (EV71) infection. The present study was designed to determine the
      characteristics of the chemokine response in the blood and cerebrospinal fluid
      (CSF) of patients with EV71-associated BE. METHODS: Thirty-one patients with BE
      were studied. They consisted of 12 with uncomplicated BE, 9 with autonomic
      nervous system (ANS) dysregulation, and 10 with pulmonary edema (PE); 13 healthy
      control subjects were also studied. Plasma and CSF concentrations of various
      chemokines were determined by a particle-based flow cytometry immunoassay.
      RESULTS: Plasma levels of interferon (IFN)-gamma-induced protein (IP)-10,
      monocyte chemoattractant protein (MCP)-1, monokine induced by IFN-gamma (MIG),
      and interleukin (IL)-8 were significantly higher in patients with PE than in
      those with uncomplicated BE. CSF levels of MIG were significantly higher in
      patients with PE than in those with uncomplicated BE and ANS dysregulation. The
      ratios of mean CSF to plasma levels for MCP-1 and IL-8 were highest in patients
      with uncomplicated BE and tended to fall with increasing severity of the disease.
      CONCLUSIONS: Overexpression of the chemokine cascade in the central nervous
      system compartment appears to play an important role in the elicitation of the
      immune response to EV71. The chemokine CSF to plasma ratios suggest that IL-8, IP
      10, MCP-1, and possibly MIG-but not RANTES-are synthesized in the brain in
      response to encephalitis.

PMID- 18710326
TI  - Planning for an influenza pandemic: thinking beyond the virus.

PMID- 18710327
TI  - Predominant role of bacterial pneumonia as a cause of death in pandemic
      influenza: implications for pandemic influenza preparedness.
AB  - BACKGROUND: Despite the availability of published data on 4 pandemics that have
      occurred over the past 120 years, there is little modern information on the
      causes of death associated with influenza pandemics. METHODS: We examined
      relevant information from the most recent influenza pandemic that occurred during
      the era prior to the use of antibiotics, the 1918-1919 "Spanish flu" pandemic. We
      examined lung tissue sections obtained during 58 autopsies and reviewed
      pathologic and bacteriologic data from 109 published autopsy series that
      described 8398 individual autopsy investigations. RESULTS: The postmortem samples
      we examined from people who died of influenza during 1918-1919 uniformly
      exhibited severe changes indicative of bacterial pneumonia. Bacteriologic and
      histopathologic results from published autopsy series clearly and consistently
      implicated secondary bacterial pneumonia caused by common upper respiratory-tract
      bacteria in most influenza fatalities. CONCLUSIONS: The majority of deaths in the
      1918-1919 influenza pandemic likely resulted directly from secondary bacterial
      pneumonia caused by common upper respiratory-tract bacteria. Less substantial
      data from the subsequent 1957 and 1968 pandemics are consistent with these
      findings. If severe pandemic influenza is largely a problem of viral-bacterial
      copathogenesis, pandemic planning needs to go beyond addressing the viral cause
      alone (e.g., influenza vaccines and antiviral drugs). Prevention, diagnosis,
      prophylaxis, and treatment of secondary bacterial pneumonia, as well as
      stockpiling of antibiotics and bacterial vaccines, should also be high priorities
      for pandemic planning.

PMID- 18710328
TI  - Comparison of molecular strategies for breast cancer virotherapy using oncolytic
      adenovirus.
AB  - Oncolytic viruses are regulated by the tumor phenotype to replicate and lyse
      cancer cells selectively. To identify optimal strategies for breast cancer we
      compared five adenoviruses with distinct regulatory mechanisms: Ad-dl922-947
      (targets G1-S checkpoint); Ad-Onyx-015 and Ad-Onyx-017 (target p53/mRNA export);
      Ad-vKH1 (targets Wnt pathway), and AdEHE2F (targets estrogen receptor/G1-S
      checkpoint/hypoxic signaling). The quantity of virus required to kill 50% of
      breast cancer cells after 6 days (EC(50), plaque-forming units per cell) was
      measured. The most potent virus was Ad-dl922-947 (EC(50), 0.01-5.4 in SkBr3, MDA
      231, MDA-468, MCF7, and ZR75.1 cells), followed by wild-type (Ad-WT; EC(50), 0.3
      5.5) and AdEHE2F (EC(50), 1.4-3.9). Ad-vKH1 (EC(50), 7.2-72.1), Ad-Onyx-017
      (EC(50), 8.4-167), and Ad-Onyx-015 (EC(50), 17.7-377) showed less activity. Most
      viruses showed limited cytotoxicity in normal human cells, including breast
      epithelium MCF10A (EC(50), >722) and fibroblasts (EC(50), >192) and only moderate
      cytotoxicity in normal microvascular endothelial cells (HMVECs; EC(50), 42.8
      149), except Ad-dl922-947, which was active in HMVECs (EC(50), 1.6). After
      injection into MDA-231 xenografts, Ad-WT, AdEHE2F, and Ad-dl922-947 showed
      replication, assessed by hexon staining and quantitative polymerase chain
      reaction measurement of viral DNA, and significantly inhibited tumor growth,
      leading to extended survival. After intravenous injection Ad-dl922-947 showed DNA
      replication (233% of the injected dose was measured in liver after 3 days)
      whereas AdEHE2F did not. Overall, AdEHE2F showed the best combination of low
      toxicity in normal cells and high activity in breast cancer in vitro and in vivo,
      suggesting that molecular targeting using estrogen response elements, hypoxia
      response elements, and a dysregulated G1-S checkpoint is a promising strategy for
      virotherapy of breast cancer.

PMID- 18710329
TI  - Genetic variants associated with insulin resistance and metabolic syndrome in
      young Asian Indians with myocardial infarction.
AB  - BACKGROUND: The objective of this study was to assess whether an association
      exists between the metabolic syndrome and polymorphisms in genes involved in
      insulin resistance in young Asian Indian patients presenting with acute
      myocardial infarction (AMI). METHODS: The study population comprised 467 patients
      who were 45 years or younger. The National Cholesterol Education Program Adult
      Treatment Panel III (NCEP ATP III) and the International Diabetes Federation
      (IDF) definitions were used to assess the prevalence of metabolic syndrome. We
      examined the genotype and allele frequencies of the IRS-I G972R, PPAR-gamma P12A,
      KCNJ11 E23K, and TNF-alpha -308G/A polymorphisms in relation to the metabolic
      syndrome determined by both definitions. RESULTS: The metabolic syndrome as
      defined by the NCEP ATP III criteria was found in 282 (60.4%) patients, and in
      278 (59.5%) patients according to the IDF criteria. This gave only a moderate
      level of agreement of 79% between the two definitions (Cohen's kappa = 0.554). No
      association was found between the IRS-I G972R, PPAR-gamma P12A, and KCNJ11 E23K,
      or TNF-alpha -308G/A polymorphic variants and the metabolic syndrome, or its
      components, for either definition. CONCLUSION: Although the metabolic syndrome is
      a common finding in young Asian Indian patients with AMI, there was only a
      moderate level of agreement between the NCEP ATP III and IDF definitions of the
      syndrome. Our findings do not support a role for any of the polymorphic variant
      alleles in the four insulin resistance-related genes examined in the etiology of
      insulin resistance and reinforces the notion of a multifactorial etiology for the
      metabolic syndrome.

PMID- 18710330
TI  - Restorative yoga in adults with metabolic syndrome: a randomized, controlled
      pilot trial.
AB  - BACKGROUND: Metabolic syndrome increases the risk of diabetes and cardiovascular
      disease. Yoga improves some metabolic parameters, but it has not been studied in
      persons with metabolic syndrome. We conducted a randomized controlled pilot trial
      to determine whether a restorative yoga intervention was feasible and acceptable
      in underactive, overweight adults with metabolic syndrome. METHODS: Twenty six
      underactive, overweight adult men and women with metabolic syndrome were
      randomized to attend 15 yoga sessions of 90 minutes each over 10 weeks or to a
      wait-list control group. Feasibility was measured by recruitment rates, subject
      retention, and adherence. Acceptability was assessed by interview and
      questionnaires. Changes in metabolic outcomes and questionnaire measures from
      baseline to week 10 were calculated. RESULTS: A total of 280 people were screened
      by phone, and 93 with high likelihood of metabolic syndrome were invited to a
      screening visit. Of the 68 who attended screening visits, 26 (38%) were
      randomized, and 24 (92%) completed the trial. Attendance at yoga classes and
      adherence to home practice exceeded our goals. In the yoga group, all
      participants gave the study the highest possible satisfaction rating, and the
      majority (87%) felt that the yoga poses were easy to perform. There was trend to
      reduced blood pressure (p = 0.07), a significant increase in energy level (p <
      0.009), and trends to improvement in well-being (p < 0.12) and stress (p < 0.22)
      in the yoga versus control group. CONCLUSIONS: Restorative yoga was a feasible
      and acceptable intervention in overweight adults with metabolic syndrome. The
      efficacy of yoga for improving metabolic parameters in this population should be
      explored in a larger randomized controlled trial.

PMID- 18710331
TI  - Could quality of life impact the prevalence of metabolic syndrome? Results from a
      population-based study of Swedish women: the Women's Health in the Lund Area
      Study.
AB  - BACKGROUND: The metabolic syndrome is regarded as an important risk factor for
      diabetes mellitus and cardiovascular disease. Metabolic syndrome could be
      associated with impaired quality of life (QoL). METHODS: The Women's Health in
      the Lund Area (WHILA) project covers 10,766 women born between December 2, 1935,
      and December 1, 1945, living in the Lund area, of Sweden by December 1, 1995. The
      primary objectives of this project were to survey perimenopausal women in this
      area and to evaluate their health status and lifestyles. We used the criteria for
      the metabolic syndrome, as defined by the National Cholesterol Education Program
      (NCEP) Adult Treatment Panel III (ATP III), which include three or more of five
      risk factors: central obesity, elevated serum triglycerides, low high-density
      lipoprotein cholesterol (HDL-C), and elevated blood pressure and fasting glucose.
      Analysis of most aspects of daily life and QoL according to the Gothenburg
      Quality of Life Instrument (GQL) was done. GQL refers to the WHO definition of
      health. RESULTS: A total number of 6913 (64.2%) women with a mean age (56.1)
      years fulfilled the criteria for screening procedure in the WHILA study. A
      positive association between women with metabolic syndrome and the following
      aspects of quality of life were found: "Partnership," "free time," "memory," and
      being "appreciated outside home." However, "economy," "health," "body image," and
      "fitness" had a negative association to the metabolic syndrome. CONCLUSION: QoL
      is an important factor for metabolic syndrome. Apart from traditional biological
      factors, prevention of metabolic syndrome should also encompass QoL.

PMID- 18710332
TI  - Trends in obesity and diabetes prevalence in a Chilean urban population: 1993
      2001.
AB  - BACKGROUND: In recent years, the Chilean population has suffered significant
      lifestyle changes associated with the rapid socioeconomic development of the
      country. These changes can induce a significant increase in the prevalence of
      some chronic diseases, such as obesity, dyslipidemia, and diabetes mellitus. We
      aimed to assess diabetes mellitus, obesity, and hypercholesterolemia trends in a
      Chilean urban population followed between 1993 and 2001. METHODS: A total of 1584
      adults, living in Santiago, the capital of Chile, were randomly enrolled in a
      cross-sectional epidemiologic study in 1993. The same population was re-evaluated
      in 2001, recruiting 964 individuals from the original sample. Prevalences of
      diabetes mellitus, obesity, and hypercholesterolemia were determined according to
      standard criteria. We tested the significance of the differences between the
      observed prevalence of diabetes mellitus, obesity, and hypercholesterolemia in
      the 964 subjects evaluated in 2001 compared with the expected prevalence
      according to population aging based in data from 1993. FINDINGS: In 1993, 3.8% of
      the sample population had diabetes mellitus, 21.8% had obesity, and 37.3 %
      exhibited hypercholesterolemia. In 2001, the observed prevalence of diabetes
      mellitus, obesity, and hypercholesterolemia was 10.1%, 32%, and 58%,
      respectively. The latter percentages were significantly higher than the expected
      prevalence according to the aging of the population (6.5% for diabetes mellitus,
      27.7% for obesity, and 47.7 for hypercholesteromia). INTERPRETATION: Our findings
      indicate that Chilean population has suffered an accelerated increase in the
      prevalence of diabetes mellitus, obesity, and hypercholesterolemia, due to the
      ongoing epidemiological transition that will lead to an enormous public health
      burden in the near future.

PMID- 18710333
TI  - Prevalence of polycystic ovary syndrome in women with type 2 diabetes in Kerman,
      Iran.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder
      characterized by chronic anovulation and hypergonadism that affects 5-10% of
      women of reproductive age. Patients with this syndrome are at high risk of
      developing type 2 diabetes mellitus in future. This study was carried out to
      determine the prevalence of PCOS in patients with type 2 diabetes mellitus.
      METHODS: One hundred consecutive women under 45 years of age with type 2 diabetes
      treated with diet or hypoglycemic drugs, referring to Kerman Diabetic Center,
      Kerman, Iran, in 2005 were identified. Patients with galactorrhea or history of
      thyroid dysfunction were excluded from the study. Data were collected through
      questionnaire-based interviews and were then analyzed. RESULTS: Ninety two women,
      of which 18 (19.5%) had clinical symptoms of PCOS, enrolled in the study. The
      mean age of subjects was 38.8 +/- 5.9 years. We found no significant relation
      between PCOS and familial type 2 diabetes or gestational diabetes. The mean body
      mass index (BMI) was 28.19 +/- 4.44 kg/m(2) in patients with PCOS and 26.06 +/-
      3.83 kg/m(2) in non-PCOS patients (p = 0.043). The prevalence of abdominal
      obesity was higher among PCOS patients than non-PCOS patients (38.9% vs. 14.8%, p
      = 0.011). CONCLUSION: In our study, abdominal obesity was more among type 2
      diabetic women with PCOS. Therefore, central or abdominal obesity might be
      considered as an important risk factor for type 2 diabetes in women with PCOS.

PMID- 18710334
TI  - Identifying the changes in gene profiles regulating the amelioration of age
      related oxidative damages in kidney tissue of rats by the intervention of adult
      onset calorie restriction.
AB  - This study was initiated to investigate gene expression profiles that are
      involved in the molecular mechanisms regulating the amelioration of age-related
      oxidative damages in male Fischer-344 rats (12 months) through adult-onset
      calorie restriction (CR) intervention for 6 months. The adult-onset CR was
      initiated with 10 and 25% restriction for the first and second weeks,
      respectively, and then maintained at 40% throughout the experiment. The adult
      onset CR significantly (p < 0.05) decreased urinary 8-isoprostane and protein
      carbonyl in kidney for the markers of lipid peroxidation and protein oxidation,
      respectively, in rats from the CR group when compared with control group. Based
      on Yu's and Melk's methods, the age-related renal pathological changes in the
      kidney of rats from CR group were retarded by adult-onset CR. Such changes could
      result from the decrease of plasminogen activation inhibition-1 and clusterin and
      the increase of kallikrein mRNA expressions significantly (p < 0.05) in the
      kidneys of rats from the CR group. They were further confirmed by quantitative RT
      PCR. Moreover, inflammatory response pathway was down-regulated significantly (p
      < 0.05) in rats from the CR group, while fatty acid synthesis, mitochondrial
      fatty acid betaoxidation, glycolysis, and gluconeogenesis were considerably up
      regulated in kidney tissue of rats. In conclusion, the adult-onset CR could
      retard the age-related oxidative damages and renal pathological changes due to
      variations in gene expressions and biological pathways.

PMID- 18710335
TI  - Improvement of culture conditions of human embryoid bodies using a controlled
      perfused and dialyzed bioreactor system.
AB  - In parallel to the active search for therapeutic and industrial applications of
      human embryonic stem cells (hESCs), designing automated means of producing those
      cells is a timely goal. Slow-turning lateral vessels (STLVs) with low shear
      stress have shown promise for expanding the cells at the embryoid body stage. We
      have improved this technology by developing two complementary systems, allowing
      continuous optimization of the culture conditions. First, perfused STLV
      bioreactors were set up, to provide continuous delivery of culture medium to the
      cells growing in the rotating chamber. This allowed the external control of the
      culture medium, and consequently optimized oxygenation, pH, nutrient supply, and
      waste elimination. Second, a dialysis chamber was adapted. This led to a further
      enhanced controlled environment and a decrease in the quantity of adjunct
      products (e.g., growth factors) necessary to the cells inside the bioreactor
      chamber. hESC aggregation and initial differentiation-taking neural induction as
      an example-were compared between the perfused and dialyzed STLV system and static
      cultures. Perfused and dialyzed STLV bioreactors promoted formation of embryoid
      bodies that were differentiated more rapidly and were homogeneously synchronized
      in a statistically significant manner.

PMID- 18710336
TI  - The effect of enamel matrix derivative (Emdogain) on bone formation: a systematic
      review.
AB  - This systematic review focused on the question, if and to what extent enamel
      matrix derivative (Emdogain) [EMD]) promotes the regeneration of bone. The
      influence of combinations with other biomaterials was additionally evaluated.
      Twenty histomorphometric studies were included in this systematic review. Main
      results of the reviewed articles were (i) guide tissue regeneration (GTR) of
      infrabony defects seems to result in a higher degree of bone regeneration
      compared to treatment with EMD; (ii) combined therapy (GTR + EMD) of infrabony
      defects might not lead to better results than GTR therapy alone; (iii) there
      seems to be no additional benefit of combined therapy (GTR + EMD) in furcation
      defects over GTR therapy alone; (iv) EMD seems to lead to more bone regeneration
      of infrabony defects compared to open flap debridement; (v) however, EMD
      application might result in more bone formation when applied in supporting
      defects compared to nonsupporting defects; and (vi) EMD does not seem to promote
      external jaw/parietal bone formation in the titanium capsule model. The results
      of one study that suggest that EMD increases the initial growth of trabecular
      bone around endosseous implants by new bone induction need to be confirmed by
      additional research.

PMID- 18710337
TI  - IL-10 secretion increases signal persistence of HEMA-MMA-microencapsulated
      luciferase-modified CHO fibroblasts in mice.
AB  - Microencapsulation of cells in a polymer membrane [e.g., poly(hydroxyethyl
      methacrylate-co-methyl methacrylate) (HEMA-MMA)] has been proposed as a vehicle
      for the delivery of therapeutic biomolecules, but cells (especially xenogeneic
      cells) survive only for short times, limiting the utility of this approach.
      Murine interleukin-10 (mIL-10) has been shown to downregulate the xenogeneic
      immune response, and we tested the hypothesis that mIL-10 produced by
      microencapsulated Chinese hamster ovary (CHO) cells would modulate the transplant
      site environment leading to prolonged cell function in a xenogeneic model without
      other immunomodulatory agents. Prior to encapsulation, CHO cells were genetically
      engineered to express mIL-10 and a firefly bioluminescence protein, luciferase,
      which allowed for noninvasive tracking of transplanted cells in vivo with the
      Xenogen IVIS Imaging System. This nondestructive imaging system was sufficiently
      sensitive to detect photon signal emitted by a single capsule containing around
      800 luciferase-transduced CHO (CHO(LUC)) cells in vitro, and to track changes in
      luciferase expression in vivo over time. Effective modulation of the
      transplantation-site environment with mIL-10 secreted from capsules was evident
      by greater luciferase expression at 10 and 21 days after transplantation relative
      to encapsulated luciferase-transfected cells that did not produce mIL-10. Longer
      duration effects require further investigation to extend this proof-of-concept
      study.

PMID- 18710338
TI  - Transmission-recovery trade-offs to study parasite evolution.
AB  - Parasite evolution is mainly studied through a trade-off involving host death
      (i.e., virulence) and transmission. In addition to the lack of evidence, this
      trade-off largely fails to understand the evolution of sublethal parasite
      effects. Here, I argue that considering host recovery as a main selection
      pressure faced by the parasite helps to address these problems and opens new
      perspectives for the study of parasite evolution. Using an embedded model, I show
      how a trade-off between transmission and recovery may emerge from within-host
      dynamics if immune activation is assumed to depend on the parasite's overall
      growth rate. I also show that the value of the parasite's optimal growth rate
      strongly depends on the immunological state of the host. Transmission-recovery
      trade-offs are of particular interest to the study of the evolution of human
      pathogens because of the use of antipathogen treatments, which strengthens the
      recovery constraint.

PMID- 18710341
TI  - Environmental effects on the expression of life span and aging: an extreme
      contrast between wild and captive cohorts of Telostylinus angusticollis (Diptera:
      Neriidae).
AB  - Most research on life span and aging has been based on captive populations of
      short-lived animals; however, we know very little about the expression of these
      traits in wild populations of such organisms. Because life span and aging are
      major components of fitness, the extent to which the results of many evolutionary
      studies in the laboratory can be generalized to natural settings depends on the
      degree to which the expression of life span and aging differ in natural
      environments versus laboratory environments and whether such environmental
      effects interact with phenotypic variation. We investigated life span and aging
      in Telostylinus angusticollis in the wild while simultaneously estimating these
      parameters under a range of conditions in a laboratory stock that was recently
      established from the same wild population. We found that males live less than one
      fifth as long and age at least twice as rapidly in the wild as do their captive
      counterparts. In contrast, we found no evidence of aging in wild females. These
      striking sex-specific differences between captive and wild flies support the
      emerging view that environment exerts a profound influence on the expression of
      life span and aging. These findings have important implications for evolutionary
      gerontology and, more generally, for the interpretation of fitness estimates in
      captive populations.

PMID- 18710342
TI  - Facultative sex ratio adjustment in natural populations of wasps: cues of local
      mate competition and the precision of adaptation.
AB  - Sex ratio theory offers excellent opportunities to examine the extent to which
      individuals adaptively adjust their behavior in response to local conditions.
      Hamilton's theory of local mate competition, which predicts female-biased sex
      ratios in structured populations, has been extended in numerous directions to
      predict individual behavior in response to factors such as relative fecundity,
      time of oviposition, and relatedness between cofoundresses and between mates.
      These extended models assume that foundresses use different sources of
      information, and they have generally been untested or have only been tested in
      the laboratory. We use microsatellite markers to describe the wild oviposition
      behavior of individual foundresses in natural populations of the parasitoid wasp
      Nasonia vitripennis, and we use the data collected to test these various models.
      The offspring sex ratio produced by a foundress on a particular host reflected
      the number of eggs that were laid on that host relative to the number of eggs
      that were laid on that host by other foundresses. In contrast, the offspring sex
      ratio was not directly influenced by other potentially important factors, such as
      the number of foundresses laying eggs on that patch, relative fecundity at the
      patch level, or relatedness to either a mate or other foundresses on the patch.

PMID- 18710343
TI  - Human monocytes augment invasiveness and proteolytic activity of inflammatory
      breast cancer.
AB  - Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer,
      and here, we examined in vitro the interactions between the human IBC cell line
      SUM149 and U937 human naive monocytes. We found an altered morphology, enhanced
      invasiveness and proteolytic activity of SUM149 cells when cultured with U937
      cells or in U937-conditioned media (U937-CM). Increases in expression and
      activity of the cysteine protease cathepsin B and expression of caveolin-1 were
      also detected in SUM149 cells grown in U937-CM, thus suggesting a contribution of
      these proteins to the augmented invasion through and proteolysis of the
      extracellular matrix by the IBC cells.

PMID- 18710344
TI  - Trial of the cysteine cathepsin inhibitor JPM-OEt on early and advanced mammary
      cancer stages in the MMTV-PyMT-transgenic mouse model.
AB  - Recent data suggest proteases of the papain-like cysteine cathepsin family as
      molecular targets for cancer therapy. Here, we report the treatment of polyoma
      middle T oncogene-induced breast cancers in mice with the cell-permeable broad
      spectrum cysteine cathepsin inhibitor JPM-OEt. Up to 100 mg/kg inhibitor was
      intraperitoneally injected once per day in two trials on early and advanced
      cancers. In both trials, transient delays in tumour growth were observed.
      However, at the endpoint of both experiments no significant differences in tumour
      weights, histopathology and lung metastasis were found between the inhibitor and
      the control group. The invasive strand formation of collagen I-embedded tumour
      cell spheroids generated from primary tumours of inhibitor-treated mice in the
      early cancer trial could be inhibited in vitro by JPM-OEt; a result arguing
      against induction of resistance to the inhibitor. Measurement of cysteine
      cathepsin activities in tissue extracts after intraperitoneal injection of JPM
      OEt revealed effective inhibition of cysteine cathepsins in pancreas, kidneys and
      liver, while activities in mammary cancers and in lungs were not significantly
      affected. We conclude that the pharmacokinetic properties of JPM-OEt, which
      result in poor bioavailability, may prohibit its use for stand-alone treatment of
      solid mammary cancers and their lung metastases.

PMID- 18710345
TI  - Isolation and characterization of multipotent human keloid-derived mesenchymal
      like stem cells.
AB  - In this study, we report the isolation and characterization of a population of
      multipotent keloid-derived mesenchymal-like stem cells (KMLSCs) from keloid scalp
      tissues. These KMLSCs expressed the typical mesenchymal stem cell marker proteins
      CD13, CD29, CD44, CD90, fibronectin, and vimentin when they were cultured in
      serum-containing medium and when subsequent exposure to various differentiation
      media resulted in their differentiation into adipocytes, osteoblasts,
      chondrocytes, smooth muscle cells, and angiogenic endothelial cells. When KMLSCs
      were cultured in neural stem culture conditions (i.e., in the presence of
      epidermal growth factor and fibroblast growth factor 2 in substrate-free
      conditions), they produced large numbers of neurospheres containing nestin-,
      CD133-, and SOX2-positive cells that expressed neural-crest stem cell markers.
      Subsequent exposure of these cells to different differentiation conditions
      resulted in cells that expressed neuronal cell-, astrocyte-, oligodendrocyte-, or
      Schwann cell-specific markers. Our study suggests that KMLSCs may be an
      alternative adult stem cell resource for regenerative tissue repair and auto
      transplantation.

PMID- 18710346
TI  - Effects of hindlimb unloading on ex vivo growth and osteogenic/adipogenic
      potentials of bone marrow-derived mesenchymal stem cells in rats.
AB  - The goal of this study was to determine the effects of hindlimb unloading (HU) on
      the ex vivo growth and the osteogenic potential of mesenchymal stem cells (MSCs)
      from the femurs of rats. Microgravity was simulated by 28-day HU in male Sprague
      Dawley (SD) rats, and the bone marrow (BM) was collected from hindlimb femurs of
      HU or control (CTL) rats. MSCs were isolated from BM and cultured for eight
      passages. Then MSCs at passages 2, 4, and 8 were induced for osteogenesis or
      adipogenesis. The results revealed that HU decreased the osteogenic potential of
      MSCs and also decreased the expression of osteoblast gene marker mRNAs in cells
      induced by osteogenic conditions. Meanwhile, the expression of Runx2 mRNA and the
      phosphorylation of ERK were also decreased. There were no significant differences
      of osteoblast gene marker and Runx2 mRNA expression between cells induced from
      different passages of MSCs in UH rats. Under adipogenic conditions, HU increased
      both the adipogenic potential of MSCs and the expression of adipocytic gene
      marker mRNAs in induced cells. HU also increased the expression of PPAR gamma 2
      mRNA, but with no effect on the phosphorylation of p38MAPK. The adipogenic
      potential of MSCs and the expression of adipocytic gene marker mRNAs in induced
      cells decreased along with cell cultures under normal gravity. This suggests that
      the normal gravity during in vitro MSC culture and the centrifugal force produced
      during cell harvest after each passage could decrease the adipogenic potential of
      MSCs, but could not reverse the effect of HU on the osteogenic potential of MSCs.

PMID- 18710347
TI  - Evaluation of the injection force dynamics of a modified prefilled insulin pen.
AB  - OBJECTIVE: A modified version of the widely used pen FlexPen (FP), called Next
      Generation FlexPen (NGFP), has been designed to reduce the injection force with
      this pen. In this study, the injection force of NGFP was compared with another
      insulin pen, SoloStar (SS). RESEARCH DESIGN/METHODS: The injection force of 24
      pens of each type: NGFP fitted with a NovoFine 32G Tip ETW 6 mm needle; SS fitted
      with a NovoFine 32G Tip needle and SS fitted with a BD Micro-Fine 31G thin wall 5
      mm needle, were tested during the delivery of 60 IU insulin at three constant
      push-button speeds - 4, 6 or 8 mm/s. RESULTS: NGFP had the lowest mean (+/-
      standard deviation) injection force at all injection speeds (8.3 +/- 0.6, 12.0 +/
      0.9 and 16.2 +/- 1.3 N at 4, 6 and 8 mm/s, respectively)--for SS fitted with a
      NovoFine 32G Tip needle the corresponding values were 10.2 +/- 1.1, 15.7 +/- 1.5
      and 22.3 +/- 1.1 N, and for SS fitted with a BD Micro-Fine 31G needle they were
      12.9 +/- 0.8, 20.5 +/- 1.3 and 29.6 +/- 1.9 N. This corresponded to an 18 - 45%
      lower injection force with NGFP. The time to complete each dose delivery
      (including the time manufacturers' recommend that the needle is left in situ
      after delivering the dose) was 14.2, 11.5 and 10.1 s with NGFP at injection
      speeds of 4, 6 and 8 mm/s, respectively, and were 16.4, 14.3 and 13.2 s with SS,
      respectively. CONCLUSIONS: This study shows that NGFP has a significantly lower
      injection force than SS at three specific push-button speeds.

PMID- 18710348
TI  - Safety, simplicity and convenience of a modified prefilled insulin pen.
AB  - OBJECTIVE: To assess patient perception of usability, safety and convenience of
      Next Generation FlexPen (NGFP), a newly modified version of the insulin delivery
      device FlexPen (FP), and the ease of attaching NovoTwist and NovoFine needles.
      RESEARCH DESIGN AND METHODS: A 35-item questionnaire was completed by patients
      with Type 1 or Type 2 diabetes to compare the visual appearance of NGFP with FP
      (prefilled with either insulin detemir, insulin aspart or biphasic insulin
      aspart), the ease or difficulty of attaching needles onto NGFP and FP, and the
      ease of use, convenience, trust and safety of NGFP and FP when used to inject 20,
      40 or 60 IU of insulin into an injection pillow. RESULTS: A total of 64 patients
      completed all questions. Most patients found the identification of the type of
      insulin easiest with NGFP based on the label, the cartridge and the packaging,
      whereas < 5% found it easier with FP. Attaching the NovoTwist needle was
      significantly easier than attaching the NovoFine needle. Patients found NGFP
      significantly easier to use than FP when injecting insulin doses of 20 IU (52%),
      40 IU (97%) and 60 IU (97%). NGFP instilled more trust and confidence than FP in
      50% of patients, and 48% had no preference. Overall, 95% of patients preferred
      NGFP to FP and 77% of patients preferred the NovoTwist needle to the NovoFine
      needle. CONCLUSIONS: Measures of usability, convenience, patient perception of
      safety and trust, and overall patient preference with NGFP, showed that this
      newly modified pen was preferred to the widely used FP.

PMID- 18710349
TI  - Pharmacotherapy of chronic viral hepatitis and hepatocellular carcinoma.
AB  - BACKGROUND: Hepatitis B virus (HBV) is a major etiologic agent of chronic liver
      disease (CLD) and hepatocellular carcinoma. Drugs have been developed and shown
      to be effective against HBV replication. These treatments are often associated
      with the resolution of CLD. However, they are too expensive, not well tolerated,
      and result in the development of resistance when given as mono or salvage
      therapies. In addition, most of these drugs target only the virus polymerase.
      OBJECTIVE: To revitalize the field, drugs with other targets and combination
      therapies need to be developed. METHODS: Major advances in HBV and liver cancer
      drug development over the past decade, focusing on Phase III trials and FDA
      approved compounds, are presented. RESULTS/DISCUSSION: A number of potent
      nucleoside/nucleotide analogs are now available for treatment, but for the long
      term management of CLD, the development of combination therapies will probably be
      required. Development of compounds with new virus targets will enhance the
      utility of combination therapies. Development of compounds to host targets
      altered prior to or after the development of liver cancer, as demonstrated by
      sorafenib, need to be developed. The goal is to devise drug cocktails that will
      yield sustained virus responses and halt disease progression and tumor
      development.

PMID- 18710350
TI  - Pharmacotherapy of large B-cell lymphoma.
AB  - BACKGROUND: Constituting approximately 30% of lymphoid malignancies, diffuse
      large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma in adults
      worldwide. The clinical and biologic heterogeneity that exists in DLBCL suggests
      that this entity might actually be comprised of several distinct neoplasms that
      could require different therapeutic approaches. DLBCL was considered incurable
      until combination chemotherapy became available. OBJECTIVE: Current treatment
      strategies for the treatment of untreated and relapsed advanced-stage DLBCL are
      reviewed; novel treatments for DLBCL are discussed. METHODS: Relevant literature
      was identified using the PubMed search engine and by reviewing abstracts from
      major conference proceedings. RESULTS/CONCLUSION: Recently, novel therapeutic
      strategies, including the incorporation of immunotherapy to combination
      chemotherapy, have improved outcome for patients with DLBCL with cure rates
      exceeding 50%, especially in younger patients.

PMID- 18710351
TI  - Pharmacotherapy of relapsed metastatic testicular cancer.
AB  - BACKGROUND: Patients with metastatic testicular cancer exhibit an excellent
      prognosis. However, the outcome for patients with relapse after cisplatin-based
      chemotherapy remains unsatisfactory. Several larger studies have been recently
      published. OBJECTIVE: To review the treatment of patients with testicular cancer
      after failure of first-line chemotherapy. METHODS: A literature search was
      performed for studies investigating therapies for relapsed testicular cancer.
      RESULTS/CONCLUSIONS: The prognosis of patients relapsing after first-line
      cisplatin-based chemotherapy has improved with multimodality therapy, including
      conventional and high-dose chemotherapy, surgery and radiation. Prognostic
      factors are increasingly used to guide treatment intensity. High-dose
      chemotherapy has become an accepted treatment option, in particular in patients
      with poor risk factors at relapse. The outcome of patients with multiply relapsed
      or cisplatin-refractory disease remains particularly poor. Treatment of relapsed
      patients requires a close cooperation of medical oncologists, urologists,
      surgeons and radiation oncologists with extensive experience in this disease.

PMID- 18710352
TI  - An update on treatment strategies for acromegaly.
AB  - BACKGROUND: Acromegaly is an insidious disease due to growth hormone (GH)
      hypersecretion from a pituitary adenoma, and is associated with multiple
      comorbidities and risk of premature mortality. OBJECTIVES: To review the
      therapeutic goals and options for acromegaly. METHODS: Literature review.
      RESULTS/CONCLUSION: Surgery is the mainstay of therapy, but a role for primary
      medical therapy using somatostatin analogs is described as well. Somatostatin
      analogs are the mainstay for medical therapy, largely in an adjuvant setting. The
      GH receptor antagonist is also used and may be considered in addition to the
      somatostatin analogs, or as second line therapy. Based on these multiple
      modalities of therapy, it should be possible to achieve biochemical control in
      almost all patients.

PMID- 18710353
TI  - Medical management of thyroid dysfunction in pregnancy and the postpartum.
AB  - BACKGROUND: Uncontrolled thyroid dysfunction in pregnancy is associated with
      adverse fetal and maternal outcomes. OBJECTIVES: To review relevant literature
      and developments in the medical management of thyroid dysfunction in pregnancy.
      RESULTS: Hyperthyroidism in pregnancy requires careful control of maternal
      disease whilst avoiding fetal hypothyroidism. Propylthiouracil is the preferred
      antithyroid drug in pregnancy although thiamazole can be used where
      propylthiouracil is unavailable. Synthetic levothyroxine is the treatment of
      choice in hypothyroidism. Patients with pre-existing hypothyroidism will
      generally require an increase in thyroxine dose in pregnancy. Most patients with
      postpartum thyroiditis will require treatment during the hypothyroid phase. Long
      term follow-up of patients with this syndrome is essential owing to the risk of
      permanent hypothyroidism. CONCLUSION: Excellent maternal and fetal outcomes can
      be achieved with appropriate management of thyroid dysfunction in pregnancy.

PMID- 18710354
TI  - The differential effects of thiazolidindiones on atherogenic dyslipidemia in type
      2 diabetes: what is the clinical significance?
AB  - BACKGROUND: Diabetic dyslipidemia is typically characterized by an increase in
      plasma triglycerides, a decrease in high-density lipoprotein cholesterol and a
      concomitant increase in atherogenic small dense low-density lipoproteins.
      Thiazolidindiones are able to lower the levels of fasting glucose and glycated
      hemoglobin significantly by improving insulin sensitivity, as well as improving
      some aspects of diabetic dyslipidemia: total cholesterol, low-density lipoprotein
      cholesterol and high-density lipoprotein cholesterol tend to increase while
      triglycerides are generally decreased. OBJECTIVE: This paper reviewed the effects
      of pioglitazone and rosiglitazone on atherogenic diabetic dyslipidemia, in
      particular on small dense low-density lipoprotein particles. METHODS: A
      literature search (by Medline and Scopus) was performed up to 15 March 2008. The
      authors also manually reviewed the references of selected articles for any
      pertinent material. RESULTS: Pioglitazone showed an additional beneficial effect
      on triglycerides, high-density lipoprotein cholesterol and the levels of small
      dense low-density lipoprotein compared to rosiglitazone. CONCLUSIONS: Since
      recent studies have suggested that these agents may also have a differential
      effect on long-term cardiovascular end-points despite similar improvements in
      glycated hemoglobin and insulin sensitivity, the different impact on atherogenic
      diabetic dyslipidemia may help to explain these findings.

PMID- 18710356
TI  - Non-contraceptive benefits of oral contraceptives.
AB  - BACKGROUND: There is increasing awareness of the opportunity that many
      contraceptive interventions may provide for additional health benefits. However,
      treatment of medical problems with oral contraceptives (OCs) is often an 'off
      label' practice. OBJECTIVE: The aim of this review is to summarize available data
      on non-contraceptive benefits of OCs. METHODS: Review of the literature. RESULTS:
      OCs have been shown to reduce the risk of ovarian, endometrial, and colorectal
      cancer. It has been suggested that OCs may be used in treatment of endometriosis,
      menorrhagia, and uterine leiomyomas. Pelvic inflammatory disease, dysmenorrhea,
      premenstrual syndrome, and acne have been shown to improve under OCs. CONCLUSION:
      OCs are important for global and female health. Besides contraception, non
      contraceptive effects of OCs are evidence based, well established, and commonly
      used in clinical practice.

PMID- 18710355
TI  - Immunomodulation and pharmacological strategies in the treatment of graft-versus
      host disease.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplantation offers great
      promise for the treatment of a variety of diseases including malignancies and
      other diseases of hematopoietic origin. However, morbidity and mortality due to
      graft-versus-host disease (GVHD) remain a major barrier to its application.
      OBJECTIVE: This review will provide an overview of the pathophysiology of GVHD
      and discuss the recent advances in GVHD management in both preclinical and
      clinical studies. METHODS: An extensive literature search on PubMed from 1995 to
      2008 was performed. RESULTS/CONCLUSION: There has been much progress in our
      understanding of GVHD and finding new means to control acute GVHD. While these
      approaches hold promise, as yet none has been able to replace the standard
      methods we may use routinely to decrease the incidence of the condition.

PMID- 18710357
TI  - Idebenone in Friedreich's ataxia.
AB  - BACKGROUND: Friedreich's ataxia is an autosomal recessive neurodegenerative
      disease where impaired mitochondrial function and excessive production of free
      radicals play a central pathogenetic role. Idebenone, a synthetic analogue of
      coenzyme Q, is a powerful antioxidant that was first administrated to
      Friedreich's ataxia patients less than 10 years ago. OBJECTIVE: The aim of this
      study was to evaluate the efficacy of idebenone administration and define the
      optimal dosage. METHODS: A critical evaluation of all open and double-blinded
      idebenone trials in Friedreich's ataxia patients was undertaken.
      RESULTS/CONCLUSIONS: Idebenone is well tolerated in paediatric and adult
      patients. Most trials demonstrated a positive effect on cardiac hypertrophy. The
      neurological function is in general not modified in adult patients, but a dose
      dependent effect was demonstrated in young Friedreich's ataxia patients. Further
      double-blinded high-dose trials should evaluate idebenone in Friedreich's ataxia
      early in the disease course.

PMID- 18710358
TI  - Anidulafungin: a drug evaluation of a new echinocandin.
AB  - BACKGROUND: Over the past two decades, the frequency and type of invasive fungal
      infections have increased greatly and thus have driven the need for new
      antifungal agents. Anidulafungin is the newest addition to the echinocandin
      armamentarium. OBJECTIVE: The intention of this review is to provide a drug
      evaluation of anidulafungin, including its spectrum of activity,
      pharmacokinetics, pharmacodynamics, clinical efficacy, adverse event profile, and
      its role in the treatment of invasive candidiasis. METHODS: A PubMed search was
      performed to gather the most current and pertinent articles. CONCLUSIONS:
      Clinical trials have demonstrated anidulafungin's efficacy and tolerability in
      invasive candidiasis. Anidulafungin is not associated with any drug-drug
      interactions and does not require dosage adjustment in patients with renal and/or
      hepatic impairment.

PMID- 18710359
TI  - Reassessment of enfuvirtide's role in the management of HIV-1 infection.
AB  - BACKGROUND: The development of new protease inhibitors, new non-nucleoside
      reverse transcriptase inhibitors and novel therapeutic drug classes has
      dramatically changed the approach to managing HIV-1 patients with multidrug
      resistant virus. This has led many clinicians to reevaluate the clinical utility
      of enfuvirtide. OBJECTIVES: To summarize recent literature on enfuvirtide and to
      reassess enfuvirtide's role in the management of HIV-1 infection. METHODS:
      MEDLINE (1990 to February Week 2 2008) and EMBASE (1990 to 2008 week 8) databases
      were searched using the following terms: 'enfuvirtide', 'Fuzeon', 'T20', 'HIV
      fusion inhibitors', and 'HIV entry inhibitor'; limits: English language.
      Reference lists of articles deemed relevant were hand searched for additional
      publications. Significant abstracts from recent international HIV conferences
      were also identified. CONCLUSION: Enfuvirtide can optimize the response to new
      combinations of HIV-1 drug regimens in multiresistant patients. Its inclusion as
      an active agent is effective but use is impacted by its high cost, inconvenient
      route of administration and cosmetic side-effect profile.

PMID- 18710360
TI  - Lopinavir/ritonavir: a protease inhibitor for HIV-1 treatment.
AB  - BACKGROUND: Lopinavir is a protease inhibitor with high specificity for HIV-1
      protease formulated with ritonavir. Numerous clinical trials have shown that
      lopinavir/ritonavir (LPV/r) is highly effective as a component of highly active
      antiretroviral therapy (HAART) regimens for HIV-1 infection. OBJECTIVE: In this
      article we provide an overview of the properties of LPV/r and the experience with
      its use in HIV-infected adults and adolescents. METHODS: We reviewed the
      literature and selected the most important published articles on LPV/r and the
      latest posters/communications presented in conferences, with particular attention
      to the clinical efficacy and tolerability of LPV/r in HIV-1 infected patients.
      CONCLUSION: LPV/r is highly effective as a component of HAART regimens for HIV-1
      infection. There is considerable experience with the drug in both treatment-naive
      and treatment-experienced patients. In general, LPV/r is well tolerated and its
      high genetic barrier to resistance favours long-term efficacy.

PMID- 18710361
TI  - Biphasic insulin aspart 30 for the treatment of type 1 diabetes mellitus.
AB  - BACKGROUND: Type 1 diabetes mellitus is associated with acute and long-term
      complications, to which pre- and postprandial hyperglycemia are independent
      contributors. The objective of this review was to evaluate evidence-based
      information using biphasic insulin aspart 30 in the treatment of type 1 diabetes
      mellitus. METHODS: The study reviewed the Cochrane Database and scientific
      literature (PubMed) published until January 2008 using the words biphasic insulin
      aspart 30 insulin or premixed aspart insulin. CONCLUSIONS: Biphasic insulin
      aspart 30 is similar in efficacy to biphasic human insulin in improving
      hemoglobin A(1c) levels, with the advantage of a better postprandial glucose
      profile. EXPERT OPINION: There is evidence supporting the efficacy and safety of
      biphasic insulin aspart 30 insulin. However, the need for well-designed clinical
      trials aimed at understanding the potential differences in safety and efficacy
      between patients with type 1 and type 2 diabetes is crucial.

PMID- 18710362
TI  - Therapeutic potential of icatibant (HOE-140, JE-049).
AB  - There is now a substantial body of work implicating bradykinin, an endogenous
      peptide neurohormone, in the pathophysiology of a variety of inflammatory
      conditions in man. Icatibant (HOE-140, JE-049), a highly selective antagonist at
      the bradykinin B2 receptor, blocks the vasodilatation and increased vascular
      permeability associated with exogenous bradykinin administration both in
      experimental models and in vivo in man. Recent attention has focused on the
      therapeutic potential of icatibant in a number of human disease states. The most
      promising of these is hereditary angioedema in which Phase III clinical trials
      have recently been completed and regulatory approval is currently being sought in
      Europe and the USA. A therapeutic role for icatibant has also been proposed in
      several other human conditions including drug-induced angioedema, airways
      disease, thermal injury, refractory ascites in patients with liver cirrhosis, and
      acute pancreatitis, although this work remains largely experimental.

PMID- 18710363
TI  - Long-term experience with deferasirox (ICL670), a once-daily oral iron chelator,
      in the treatment of transfusional iron overload.
AB  - BACKGROUND: Chronic iron overload from frequent blood transfusions to treat
      patients with severe anaemias leads to significant morbidity and mortality. While
      deferoxamine, the current standard of care, is an effective iron chelator, it
      requires subcutaneous infusion for 8-12 h/day, 5-7 days/week. This regimen is
      problematic and impacts significantly on patients' daily life. OBJECTIVE: To
      evaluate the efficacy and tolerability of deferasirox, a once-daily oral iron
      chelator. METHOD: To review the available data reported in peer-reviewed journals
      (using PubMed) and at medical conferences. RESULTS/CONCLUSIONS: Deferasirox is
      effective in reducing or maintaining iron burden in patients with transfusion
      dependent anaemias. As deferasirox is orally administered, the inconvenience of
      parenteral administration with deferasirox is avoided. Deferasirox improves
      patient satisfaction and is expected to improve compliance with iron chelation
      therapy.

PMID- 18710364
TI  - Dissecting the nutrigenomics, diabetes, and gastrointestinal disease interface:
      from risk assessment to health intervention.
AB  - The promise of nutrigenomics is of personalized nutrition that will lead to
      optimization or maintenance of good health and/or prevention of the development
      of chronic diseases. Type 2 diabetes mellitus (T2DM) is a leading health problem
      throughout the world. Adherence to a Mediterranean-style diet, regulation of
      carbohydrate intake, and regular exercise may be desirable. Four key genes were
      originally identified: KCNJ11, potassium inwardly rectifying channel, subfamily
      J, member 11 gene; PPAR-gamma, peroxisome proliferator activated receptor-gamma;
      TCF2, transcription factor 2, hepatic; WFS1, Wolfram syndrome 1. However, genome
      wide association studies are accelerating our knowledge of the genetics of
      complex diseases, and have identified seven other key genes in T2DM: CDKAL1, CDK5
      regulatory subunit associated protein-like 1; CDKN2, cyclin-dependent kinase
      inhibitor 2A; FTO, fat mass and obesity associated; HHEX, haematopoietically
      expressed homeobox; IDE, insulin-degrading enzyme; IGF2BP2, insulin-like growth
      factor 2 mRNA-binding protein 2; SLC30A8, solute carrier family 30 (zinc
      transporter), member 8; TCF7L2, transcription factor 7-like 2 (T-cell specific,
      HMG-box). Gene-nutrient or gene-environment interactions may be important. For
      example, the PPAR-gamma variant genotype is responsive to different types and
      levels of lipids, while the effect of the FTO variant can be partly overcome by
      exercise. Several of these genes act through their effect on the gastrointestinal
      tract. There are analytical challenges in analyzing the high-dimensional datasets
      relating genes, nutrients, and other variables to their influence on health and
      disease processes. An even greater challenge may be in implementing population
      level changes in diet and behavior to fully exploit the potential of this field.

PMID- 18710365
TI  - The psychoneuroimmunology of postpartum depression.
AB  - Postpartum depression (PPD) is a potentially debilitating disorder that develops
      in a significant percentage of women during the first year after giving birth.
      Women afflicted with PPD experience long-term consequences, including sadness,
      guilt, and despair. Offspring may be affected as well. Several investigators have
      tested psychosocial risk factors for the development of PPD; however, substantial
      amounts of variance in PPD have gone unexplained with regression on psychosocial
      variables alone. Likewise, interventions for PPD that have focused on
      psychosocial risk factors alone have been largely unsuccessful. The unexplained
      variance and disappointing treatment success could well be due to investigators'
      failure to address relevant biological changes occurring during the postpartum
      period. Two biological systems that are affected significantly and remain in flux
      during the postpartum period are the innate immune system and the hypothalamic
      pituitary-adrenal (HPA) axis. Bidirectional interactions between these two
      systems are well established, and it is generally acknowledged that dysfunction
      in either system can lead to depression in nonpregnant, nonpostpartum
      populations. To date, little research has pursued the contribution of these
      interacting systems to the development of PPD. The purpose of this paper is to
      review the psychoneuroimmunology of PPD. The central hypothesis presented is that
      dysregulation in either system individually or in their bidirectional interaction
      is associated with the development of PPD.

PMID- 18710366
TI  - Alcohol abuse risk factors and psychiatric disorders in pregnant women with a
      history of infertility.
AB  - OBJECTIVE: To determine if a history of infertility is associated with alcohol
      abuse risk factors, depression, and other psychiatric disorders. METHODS:
      Pregnant women awaiting their first prenatal visit completed a questionnaire and
      subsequently participated in an interview consisting of the Structured Clinical
      Interview for DSM-IIIR and the Family Alcohol and Drug Survey. The data obtained
      from women with a history of infertility were compared with the data from women
      without prior infertility. RESULTS: Eighty-nine pregnant women participated in
      the study, 27 with prior infertility and 62 without. Subjects were
      demographically similar, except that women with a history of infertility were
      slightly older than controls (34.7 vs. 31.1 years, p < 0.001). Pregnant women
      with a history of infertility reported needing significantly more drinks to get
      high, (3.3 vs. 2.7, p = 0.04) and were more likely to have clinically elevated
      tolerance, annoyance, cut-down, and eye-opener (T-ACE) alcohol tolerance scores
      (83.3% vs. 52.3%, p < 0.01) than women without such history. Major depression
      (lifetime) was diagnosed in 69.2% of infertility subjects compared with 30% of
      controls (p < 0.05). Lifetime simple phobia (23.1% vs. 10%, p < 0.01),
      generalized anxiety disorder (23.1% vs. 3%, p < 0.01), panic disorder (15.4% vs.
      0%, p < 0.05), and bulimia (7.7% vs. 0%, p < 0.05) were also more common in women
      with a history of infertility compared with controls. CONCLUSIONS: Pregnant women
      with a history of infertility are at increased risk for alcohol abuse and are
      more likely to suffer from other psychiatric disorders than women without such
      history. Special attention to these issues is warranted when caring for pregnant
      women who were previously infertile.

PMID- 18710367
TI  - Sleep disorders and medical conditions in women. Proceedings of the Women & Sleep
      Workshop, National Sleep Foundation, Washington, DC, March 5-6, 2007.
AB  - Sleep disorders affect women differently than they affect men and may have
      different manifestations and prevalences. With regard to obstructive sleep apnea
      (OSA), variations in symptoms may cause misdiagnoses and delay of appropriate
      treatment. The prevalence of OSA appears to increase markedly after the time of
      menopause. Although OSA as defined by the numbers of apneas/hypopneas may be less
      severe in women, its consequences are similar and perhaps worse. Therapeutic
      issues related to gender should be factored into the management of OSA. The
      prevalence of insomnia is significantly greater in women than in men throughout
      most of the life span. The ratio of insomnia in women to men is approximately
      1.4:1.0, but the difference is minimal before puberty and increases steadily with
      age. Although much of the higher prevalence of insomnia in women may be
      attributable to the hormonal or psychological changes associated with major life
      transitions, some of the gender differences may result from the higher prevalence
      of depression and pain in women. Insomnia's negative impact on quality of life is
      important to address in women, given the high relative prevalence of insomnia as
      well as the comorbid disorders in this population. Gender differences in etiology
      and symptom manifestation in narcolepsy remain understudied in humans. There is
      little available scientific information to evaluate the clinical significance and
      specific consequences of the diagnosis of narcolepsy in women. Restless legs
      syndrome (RLS) is characterized by an urge to move the legs or other limbs during
      periods of rest or inactivity and may affect as much as 10% of the population.
      This condition is more likely to afflict women than men, and its risk is
      increased by pregnancy. Although RLS is associated with impaired quality of life,
      highly effective treatment is available.

PMID- 18710368
TI  - Influence of sex on sleep regulatory mechanisms.
AB  - The ability of biological sex and sex-driven characteristics to alter sleep
      states may contribute to gender disparities in sleep disorders. Sex influences
      sleep-wake amount, the daily timing of the sleep-wake cycle, and the ability to
      restore sleep after extended wakefulness. Several lines of evidence suggest that
      in mammals, reproductive hormones are responsible for the effects of sex on sleep
      and may have organizational and activational influences on sleep regulatory
      mechanisms. In humans, exogenously administered estrogens and progestins
      generally enhance sleep amount and continuity, whereas androgens appear to have a
      positive impact on rapid eye movement (REM) sleep but disrupt sleep
      consolidation. In rodent studies, however, female reproductive hormones appear to
      enhance wakefulness, and male gonadal hormones reinforce sleep. Rodent studies
      have also revealed that neonatal exposure to reproductive hormones organizes
      adult sleep-wake architecture. This paper reviews how sex and reproductive
      hormones interact with circadian and homeostatic sleep regulatory mechanisms in
      humans and animal models. We examine the organizational and activational nature
      of these interactions and also review how these interactions change with
      advancing age. Finally, we discuss the potential for genetic sex to influence
      sleep states. It is our hope that a better understanding of the mechanisms
      through which sex influences sleep-wake states will lead to improvements in the
      design of studies that examine gender disparities in sleep-wake disorders.

PMID- 18710369
TI  - Women and sleep.
AB  - A woman's sleep is impacted by biology (menstrual cycle, pregnancy, menopause),
      sleep disorders (that may manifest differently than in men), and role in the home
      and workplace. A Women and Sleep Workshop, sponsored by the National Sleep
      Foundation, in March 2007 reviewed these topics. It was concluded that
      understanding the relationship between sleep and gender will result in a
      scientifically based approach to women's sleep problems.

PMID- 18710370
TI  - Ajuba: a new microtubule-associated protein that interacts with BUBR1 and Aurora
      B at kinetochores in metaphase.
AB  - BACKGROUND INFORMATION: The role of the LIM-domain-containing protein Ajuba was
      initially described in cell adhesion and migration processes and recently in
      mitosis as an activator of the Aurora A kinase. RESULTS: In the present study, we
      show that Ajuba localizes to centrosomes and kinetochores during mitosis. This
      localization is microtubule-dependent and Ajuba binds microtubules in vitro. A
      microtubule regrowth assay showed that Ajuba follows nascent microtubules from
      centrosomes to kinetochores. Owing to its contribution to mitotic commitment and
      its microtubule-dependent localization, Ajuba could also play a role during the
      metaphase-anaphase transition. We show that Ajuba interacts with Aurora B and
      BUBR1 [BUB (budding uninhibited by benomyl)-related 1], two major components of
      the mitotic checkpoint. Inhibition of BUBR1 by siRNA (small interfering RNA)
      disrupts chromosome alignment at the metaphase plate and modifies Ajuba
      localization due to premature mitotic exit. CONCLUSIONS: Ajuba is a microtubule
      associated protein that collaborates with Aurora B and BUBR1 at the metaphase
      anaphase transition and this may be important to ensure proper chromosome
      segregation.

PMID- 18710371
TI  - The impact of PCMR.

PMID- 18710372
TI  - Effectively targeting BRAF in melanoma: a formidable challenge.

PMID- 18710374
TI  - Nursing documentation for communicating and evaluating care.
AB  - AIMS: To investigate the utility of electronic nursing documentation by exploring
      to what extent and for what purpose general practitioners use nursing
      documentation and to what extent and in which cases care unit managers use
      nursing documentation for quality development of care. BACKGROUND: As health care
      includes multidisciplinary activities, communication about the care given is
      essential. To assure delivery of good and safe care, quality development is
      necessary. The main tool available for communication and quality development is
      the patient record. In many studies, nursing documentation has been found to be
      inadequate for this purpose. DESIGN: This study had a cross-sectional descriptive
      design. METHODS: Data were collected by postal questionnaires, one to the general
      practitioners (n = 544) and one to care unit managers (n = 82) in primary health
      care. Data were analysed by descriptive statistical and qualitative content
      analysis. RESULTS: The general practitioners usually used the nursing record as
      the foremost source of information for treatment follow-up. The results, however,
      point out weaknesses and shortcomings in the nursing records, such as
      difficulties in finding important information because of a huge amount of routine
      notes. The care unit managers generally (74%) used the record for statistical
      purposes, while only half of them used it to evaluate care. CONCLUSION: Nursing
      records need more clarity and need to be more prominent regarding specific
      nursing information to fulfil their purpose of transferring information and to
      constitute a base for quality development of care. RELEVANCE TO CLINICAL
      PRACTICE: The results of this study can provide a part of a basis upon which a
      multi-professional patient record could be developed and which could also
      function as an alarm to managers at different levels to prioritize the
      development of nursing documentation.

PMID- 18710373
TI  - The antidepressant sertraline downregulates Akt and has activity against melanoma
      cells.
AB  - Melanoma is a common malignancy which is poorly responsive to chemotherapy and
      radiation. One of the major reasons melanoma responds poorly to these modalities
      is constitutive expression of Akt, which protects against apoptosis. The
      antidepressant sertraline was found to be a potent cytotoxic agent against A375
      human melanoma. To determine the mechanism by which sertraline kills melanoma
      cells, Western blot analysis of signaling molecules, including phosphorylated
      Akt, caspase 9 and phospho-p70 S6 kinase was performed. Finally, the effects of
      sertraline on A375 xenografts in mice were assessed. Sertaline potently inhibited
      the phosphorylation of Akt, and caused cell death through induction of
      endoplasmic reticulum in vitro. Sertraline monotherapy demonstrated activity
      against A375 xenografts in vivo. Akt is a major cause of resistance of melanoma
      to current therapy. Antidepressants are commonly used to prevent interferon
      induced depression. Use of antidepressants that decrease Akt may improve the
      efficacy of interferon and other therapies against melanoma. Further studies are
      needed to elucidate whether sertraline acts as an Akt inhibitor in melanoma.

PMID- 18710375
TI  - Achieving therapeutic clarity in assisted personal body care: professional
      challenges in interactions with severely ill COPD patients.
AB  - AIM AND OBJECTIVES: This paper aims to present a theoretical account of
      professional nursing challenges involved in providing care to patients suffering
      from chronic obstructive pulmonary disease. The study objectives are patients'
      and nurses' expectations, goals and approaches to assisted personal body care.
      BACKGROUND: The provision of help with body care may have therapeutic qualities
      but there is only limited knowledge about the particularities and variations in
      specific groups of patients and the nurse-patient interactions required to
      facilitate patient functioning and well-being. For patients with severe chronic
      obstructive pulmonary disease, breathlessness represents a particular challenge
      in the performance of body care sessions. DESIGN: We investigated nurse-patient
      interactions during assisted personal body care, using grounded theory with a
      symbolic interaction perspective and a constant comparative method. METHODS:
      Twelve cases of nurse-patient interactions were analysed. Data were based on
      participant observation, individual interviews with patients and nurses and a
      standardized questionnaire on patients' breathlessness. FINDINGS: Nurses and
      patients seemed to put effort into the interaction and wanted to find an
      appropriate way of conducting the body care session according to the patients'
      specific needs. Achieving therapeutic clarity in nurse-patient interactions
      appeared to be an important concern, mainly depending on interactions
      characterized by: (i) reaching a common understanding of the patient's current
      conditions and stage of illness trajectory, (ii) negotiating a common scope and
      structuring body care sessions and (iii) clarifying roles. CONCLUSION: It cannot
      be taken for granted that therapeutic qualities are achieved when nurses provide
      assistance with body care. If body care should have healing strength, the actual
      body care activities and the achievement of therapeutic clarity in nurses'
      interaction with patients' appear to be crucial. RELEVANCE TO CLINICAL PRACTICE:
      The paper proposes that patients' integrity and comfort in the body care session
      should be given first priority and raises attention to details that nurses should
      take into account when assisting severely ill patients.

PMID- 18710376
TI  - The spectrum of barriers to and facilitators of research utilization in Iranian
      nursing.
AB  - AIM: The focus of the study is the identification of barriers to and facilitators
      of research utilization in nursing practice from the perspective of Iranian
      nurses. BACKGROUND: In Iran, research utilization is a new phenomenon thus our
      knowledge with regard to those factors that promote or discourage research use is
      limited. No overall picture of the state of research utilization in Iran
      therefore exists. METHOD: A descriptive design is used. The questionnaire was
      distributed to 410 nurses from educational hospitals and nursing schools
      affiliated with Tehran Medical Sciences University in Iran. RESULTS: The major
      barriers to research utilization were that the nurses do not have time to read
      research; facilities are inadequate for implementation; and nurses do not feel
      they have enough authority to change patient care procedures. Findings revealed a
      number of facilitators which were categorised into two main groups of human
      resources and individual/organisational factors. CONCLUSION: The healthcare
      system in Iran does not provide the incentive for nurses to engage in research or
      to avail themselves of research findings. Also, time is the major issue owing to
      a nursing shortage. If research utilization is to increase in Iran, therefore,
      the most important organisational change that needs to occur is the provision of
      available facilities for nurses to use research evidence. RELEVANCE TO CLINICAL
      PRACTICE: Key factors that need attention in implementing research results into
      practice are suggested. Clearly, identification of barriers and facilitators is
      useful potentially to overcome barriers and enforce facilitators and this could
      ultimately improve nursing practice.

PMID- 18710377
TI  - Research priorities in nursing--a Delphi study among Swedish nurses.
AB  - AIMS AND OBJECTIVES: The main aim was to illuminate essential areas for future
      patient-related nursing research. The secondary aim was to stimulate nurses to
      explore important research areas based on clinical practice. BACKGROUND: Priority
      setting is regarded as one of the main strategies to ensure excellence in nursing
      science, to direct nursing research and develop healthcare practice accordingly
      as well as strengthening the nursing profession's research commitment. DESIGN AND
      METHOD: A three-round Delphi survey was conducted. A panel of 118 clinicians, in
      various nursing, teaching and administrative positions participated. Ninety-five
      panel members completed all three rounds (81%). The majority were female, aged 25
      67 (mean 49) years, with an average of 23 (range 1-40) years in nursing, working
      in hospitals (42%), primary healthcare centres, community care (44%) and
      administration/education (14%). Sixty-six per cent had graduate diplomas and 34%
      had an academic education, ranging from bachelors' to doctoral degrees. RESULTS:
      Three hundred and eighty nursing research areas were identified, evaluated and
      ranked using content analysis and descriptive statistics. The participants'
      prioritized research aimed at preserving humanistic values and developing cross
      organisational collaboration in the healthcare system. Nursing research aimed at
      preserving human dignity in geriatric care, respectful transfers, continuity of
      care and exploring the characteristics of a caring encounter were ranked high
      relative to the patient welfare, to the healthcare organisation and to the
      nursing profession. CONCLUSIONS: Nurses prioritize research that will improve
      clinical practice, assure patients' wellbeing and a caring environment. Nurses
      can reach consensus on the objectives of patient-related nursing research despite
      differences in age, workplace, educational period and level of academic degree.
      Relevance to clinical practice. When prioritizing important areas for patient
      related nursing research, informed nursing practitioners' commitment initiates
      knowledge development within clinical practice from a nursing science perspective
      as well as expanding cross-professional and cross-organisational collaboration.

PMID- 18710380
TI  - A family with hereditary hyperferritinaemia cataract syndrome: evidence of
      incomplete penetrance and clinical heterogeneity.

PMID- 18710381
TI  - Does thrombophilia testing help in the clinical management of patients?
AB  - Thrombophilia can be identified in about half of all patients presenting with
      venous thrombosis. Testing has increased tremendously for various indications,
      but whether the results of such tests help in the clinical management of patients
      has not been settled. Here, we review the most commonly tested thrombophilic
      abnormalities, i.e. protein C, protein S, and antithrombin deficiencies, the F5
      R506Q (factor V Leiden) and F2 G20210A (prothrombin G20210A) mutations, and
      elevated levels of coagulation factor VIII, and their association with venous and
      arterial thrombosis as well as pregnancy complications. We conclude that testing
      for hereditary thrombophilia generally does not alter the clinical management of
      patients with venous or arterial thrombosis or pregnancy complications. Because
      testing for thrombophilia only serves limited purpose this should not be
      performed on a routine basis.

PMID- 18710379
TI  - Allogeneic transplantation for Hodgkin lymphoma.
AB  - The majority of patients with Hodgkin lymphoma (HL) can now expect to be cured
      with conventional chemo- and/or radio-therapy. However, a subgroup still exists
      that have poor outcomes, even following dose escalation and autologous stem cell
      transplantation. Furthermore, patients relapsing after autografting have limited
      therapeutic options available. Whilst the application of allogeneic
      transplantation strategies has historically been limited by prohibitive
      transplant-related mortality, the exploration of reduced intensity approaches has
      demonstrated the feasibility of delivering allogeneic immunotherapies with more
      acceptable mortality rates. Although its role remains controversial, we are
      beginning to re-evaluate the use of allogeneic transplantation in the management
      of patients with HL and to address a number of critical questions. These include
      whether a clinically relevant graft-versus-tumour response occurs in HL, and
      whether subgroups of patients who might benefit from allogeneic approaches can be
      identified in order to inform development of rational clinical studies. This
      review focuses on evaluating recent experience with reduced intensity allogeneic
      approaches in HL in order to inform opinion on its current role and to highlight
      areas for future investigation.

PMID- 18710378
TI  - Status of minimal residual disease testing in childhood haematological
      malignancies.
AB  - In children with acute leukaemia, measurements of minimal residual disease (MRD)
      provide unique information on treatment response and have become a crucial
      component of contemporary treatment protocols. In acute lymphoblastic leukaemia
      (ALL), the most useful MRD assays are based on polymerase chain reaction (PCR)
      amplification of antigen-receptor genes, and on flow cytometric detection of
      abnormal immunophenotypes. The latter is the only MRD assay available for most
      patients with acute myeloid leukaemia (AML). PCR amplification of chromosomal
      breakpoints and fusion transcripts can also be used to track MRD in a minority of
      patients with ALL or AML. Because of the strong correlation between MRD levels
      and risk of relapse, several ongoing regimens include treatment intensification
      for children with higher MRD. Treatment de-intensification for patients with
      early MRD clearance is also being tested. In addition to their direct clinical
      application, MRD measurements can be used to better understand the molecular and
      cellular mechanisms of drug resistance in vivo. The identification of new markers
      of leukaemia and the use of increasingly sophisticated technologies for detection
      of rare cells should further facilitate routine monitoring of MRD and elucidate
      the features of drug-resistant leukaemic cells.

PMID- 18710382
TI  - Chronic lymphocytic leukaemia: an overview of aetiology--comment.

PMID- 18710384
TI  - Rituximab as treatment for minimal residual disease in hairy cell leukaemia:
      extended follow-up.

PMID- 18710383
TI  - Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and
      the Caribbean.
AB  - Neutropenia associated with race/ethnicity has essentially been unexplained and,
      although thought to be benign, may affect therapy for cancer or other illnesses.
      A recent study linked a single nucleotide polymorphism (SNP) (rs2814778) in the
      Duffy antigen/receptor chemokine gene (DARC) with white blood cell count. We
      therefore analysed the association of the rs2814778 CC, TC and TT genotypes with
      absolute neutrophil count (ANC) among asymptomatic women from the Caribbean,
      Europe and the United States. Among 261 study participants, 33/47 women from
      Barbados/Trinidad-Tobago, 34/49 from Haiti, 26/37 from Jamaica, and 29/38 US-born
      black women, but only 4/50 from the Dominican Republic and 0/40 US- or European
      born whites (P = 0.0001) had the CC genotype. In a linear regression model that
      included percentage African ancestry, national origin, cytokines, socio-economic
      factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C
      reactive protein were associated with ANC (P < 0.0001). Women with the CC
      genotype had lower ANC than other women. Further research is needed on the
      associations of rs2814778 genotype with neutropenia and treatment delay in the
      setting of cancer. A better understanding of these associations may help to
      improve cancer outcomes among individuals of African ancestry.

PMID- 18710385
TI  - Polymorphisms of the Z protein protease inhibitor and risk of venous
      thromboembolism: a meta-analysis.
AB  - Two nonsense polymorphisms of Z-dependent protease inhibitor (ZPI; Serpina10)
      have been identified. To assess the risk of venous thromboembolism (VTE)
      associated with W303x and R67X Serpina10 mutations, we performed a meta-analysis
      of studies comparing the prevalence of these two mutations in VTE patients and in
      controls Odds Ratios (ORs) and 95% confidence intervals (CIs) were calculated for
      each trial and pooled using a random-effects model. Five studies involving 5000
      patients were included. R67X and W303X mutations of Serpina10 were not associated
      with increased VTE risk (OR 1.63; 95% CI 0.84, 3.16 and OR 1.21; 95% CI 0.29,
      4.98 respectively).

PMID- 18710387
TI  - Entecavir as a first-line treatment for HBV reactivation following
      polychemotherapy for lymphoma.

PMID- 18710386
TI  - Serum autotaxin measurement in haematological malignancies: a promising marker
      for follicular lymphoma.
AB  - Autotaxin (ATX) is a tumour cell motility-stimulating factor originally isolated
      from melanoma cell supernatants. ATX is identical to lysophospholipase D, which
      produces a bioactive lipid mediator, lysophosphatidic acid (LPA), from
      lysophosphatidylcholine. ATX is overexpressed in various malignancies, including
      Hodgkin lymphoma, and ATX may stimulate tumour progression via LPA production.
      The present study measured the serum ATX antigen levels in patients with
      haematological malignancies using a recently developed automated enzyme
      immunoassay. The serum ATX antigen levels in patients with B-cell neoplasms,
      especially follicular lymphoma (FL), were higher than those in healthy subjects.
      Serum ATX antigen levels in FL patients were associated with tumour burden and
      changed in parallel with the patients' clinical courses. The serum ATX antigen
      levels were little affected by inflammation, unlike the soluble interleukin-2
      receptor and beta2-microglobulin levels. As expected, the plasma LPA levels in FL
      patients were correlated with the serum ATX antigen levels. Given that leukaemic
      tumour cells from FL patients expressed ATX, the shedding of ATX from lymphoma
      cells probably leads to the elevation of serum ATX antigen levels. Our results
      suggest that the serum ATX antigen level may be a promising and novel marker for
      FL.

PMID- 18710388
TI  - Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in
      familial hemophagocytic lymphohistiocytosis.
AB  - Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive
      lethal condition characterized by fever, cytopenia, hepatosplenomegaly and
      hemophagocytosis. The hallmark of FHL is defect apoptosis triggering and
      lymphocyte cellular cytotoxicity. Thus far three disease-causing genes (PRF1,
      UNC13D, STX11) have been identified. We performed a genotype-phenotype study in a
      large, multi-ethnic cohort of 76 FHL patients originating from 65 unrelated
      families. Biallelic mutations in PRF1, UNC13D and STX11 were demonstrated in
      13/74 (18%), 6/61 (10%) and 14/70 (20%) patients, respectively. In 27/60 (45%)
      patients analyzed for all three genes, no molecular diagnosis was established.
      STX11 mutations were most common in Turkish families (7/28, 25%), whereas in
      Middle East families, PRF1 mutations were most frequent (6/13, 46%). No biallelic
      mutation was identified in most families of Nordic origin (13/14, 93%). Patients
      carrying PRF1 mutations had higher risk of early onset (age <6 months) compared
      to patients carrying STX11 mutations [adjusted odds ratio 8.23 (95% confidence
      interval [CI] = 1.20-56.40), P = 0.032]. Moreover, patients without identified
      mutations had increased risk of pathological cerebrospinal fluid (CSF) at
      diagnosis compared to patients with STX11 mutations [adjusted odds ratio 26.37
      (CI = 1.90-366.82), P = 0.015]. These results indicate that the disease-causing
      mutations in FHL have different phenotypes with regard to ethnic origin, age at
      onset, and pathological CSF at diagnosis.

PMID- 18710389
TI  - Reduction of B cell turnover in chronic lymphocytic leukaemia.
AB  - Whether chronic lymphocytic leukaemia (CLL) is a latent or a proliferating
      disease has been intensively debated. Whilst the dogma that CLL results from
      accumulation of dormant lymphocytes is supported by the unresponsiveness of
      leukaemic cells to antigens and polyclonal activators, recent in vivo kinetic
      measurements indicate that B lymphocytes do divide at significant rates in CLL.
      However, an important and still unanswered question is whether CLL cells
      proliferate faster or slower compared with their normal counterparts. This report
      addressed directly this point and compared B-cell kinetics in CLL subjects and
      healthy controls, using a pulse-chase approach based on incorporation of
      deuterium from 6,6-(2)H(2)-glucose into DNA. We confirmed that B cells
      proliferated at significant levels in CLL but found that the proliferation rates
      were reduced compared with healthy subjects (mean 0.47 vs. 1.31%/d respectively,
      P = 0.007), equivalent to an extended doubling time of circulating B cells (147 d
      vs. 53 d). In conclusion, CLL B cells proliferate at reduced levels compared with
      healthy controls. CLL is thus characterized by an aberrant B-cell kinetics with a
      decrease in cell turnover, an observation that may impact on elaboration of
      efficient therapeutic strategies.

PMID- 18710390
TI  - High efficacy with five days schedule of oral fludarabine phosphate and
      cyclophosphamide in patients with previously untreated chronic lymphocytic
      leukaemia.
AB  - A multicentre single-arm study testing the efficacy and toxicity of the oral
      combination of fludarabine and cyclophosphamide (FC) over 5 d in 75 patients with
      untreated B cell-chronic lymphocytic leukaemia. Oral FC demonstrated high
      efficacy with overall (OR) and complete response (CR) rates of 80% and 53%,
      respectively. Out of the 30 CR patients studied for Minimal Residual Disease
      (MRD) using 4-colour flow-cytometry and the 22 using Clonospecific polymerase
      chain reaction, 22 (66%) and 16 (68%), respectively, were MRD negative. Median
      survival and median treatment-free interval had not been reached at 7 years of
      follow-up. Median progression-free survival (PFS) was 5 years. Toxicity was
      acceptable, with 52% and 16% of National Cancer Institute grade 3/4 neutropenia
      and infections, respectively. Gastrointestinal toxicity was mild. Oral FC
      demonstrated a high efficacy and an acceptable safety profile and may be
      considered as the standard first line treatment in chronic lymphocytic leukaemia.

PMID- 18710391
TI  - Isolated tongue amyloid in a patient with multiple myeloma.

PMID- 18710392
TI  - Recurrent episodes of fever and pancytopenia due to haemophagocytosis during
      maintenance therapy for acute myeloid leukaemia.

PMID- 18710393
TI  - Interphase cytogenetics for 1p19q and t(1;19)(q10;p10) may distinguish
      prognostically relevant subgroups in extraventricular neurocytoma.
AB  - Co-deletion of chromosome arms 1p and 19q, characteristic of oligodendroglial
      tumors, was recently found to be mediated by t(1;19)(q10;p10). To evaluate the
      prevalence of 1p19q co-deletion and t(1;19) in extraventricular neurocytomas
      (EVN), we studied tumors from 23 patients, including 13 females and 10 males
      (median age at diagnosis 34 years, range 2-76 years). Fluorescence in situ
      hybridization (FISH) studies were performed with probes targeting 1p36/1q25 and
      19q13/19p13 to assess for 1p19q co-deletion, as well as chromosome 1 alpha
      satellite and 19p12 to detect t(1;19)(q10;p10). FISH was successful in 21 (91%)
      cases and demonstrated 1p19q co-deletion in five cases (24%) or isolated 1p loss
      in two cases (10%). Evidence for t(1;19) was found in four (of five) cases with
      1p19q co-deletion. Three tumors with 1p19q loss and t(1;19) demonstrated atypical
      histologic features, compared with one (of 17) tumors without 1p19q co-deletion
      (P = 0.01, Fisher exact test). In addition, tumors with t(1;19) showed increased
      mitotic activity compared with tumors without t(1;19) (P = 0.045; Wilcoxon rank
      sum test). The four patients with t(1;19) developed tumor recurrence (n = 3), or
      expired (n = 2) 3.5 to 5.5 years after first resection. These results suggest
      that 1p19q loss and t(1;19) occur in a subset of EVN, and may be associated with
      aggressive histology in these tumors.

PMID- 18710394
TI  - Effect of exogenous extracellular polysaccharides on the desiccation and freezing
      tolerance of rock-inhabiting phototrophic microorganisms.
AB  - Two major stresses that threaten rock-inhabiting microbial communities are
      desiccation and freezing; both result in a loss of liquid water in the cells. The
      mechanisms necessary to tolerate these extremes may be similar, but are not well
      understood. In both cases extracellular polysaccharides (EPS) seem to play an
      important role. This study examines whether the EPS released by a rock-inhabiting
      phototroph can have a protective effect on other members of similar and
      neighboring microbial communities. This interaction was modeled by adding EPS
      isolated from the cryptoendolithic cyanobacterium Nostoc sp. to cells of the
      cryptoendolithic green alga Chlorella sp. and to cells of the epilithic
      cyanobacterium Chroococcidiopsis sp. The cells were then subjected to desiccation
      and freezing and the survival rates were determined by vital staining, using
      membrane integrity as a measure of viability. The results clearly demonstrate the
      importance of exogenous EPS in the desiccation tolerance of both species, while
      mixed results were found for the freezing trials.

PMID- 18710395
TI  - Influence of temperature and soil water content on bacterial, archaeal and
      denitrifying microbial communities in drained fen grassland soil microcosms.
AB  - In this study, microcosms were used to investigate the influence of temperature
      (4 and 28 degrees C) and water content (45% and 90% WHC) on microbial communities
      and activities in carbon-rich fen soil. Bacterial, archaeal and denitrifier
      community composition was assessed during incubation of microcosms for 12 weeks
      using terminal restriction fragment length polymorphism (T-RFLP) profiling of 16S
      rRNA and nitrous oxide reductase (nosZ) genes. In addition, microbial and
      denitrifier abundance, potential denitrification activity and production of
      greenhouse gases were measured. No detectable changes were observed in prokaryote
      or denitrifier abundance. In general, cumulatively after 12 weeks more carbon was
      respired at the higher temperature (3.7 mg CO(2) g(-1) soil), irrespective of the
      water content, whereas nitrous oxide production was greater under wet conditions
      (98-336 microg N(2)O g(-1) soil). After an initial lag phase, methane emissions
      (963 microg CH(4) g(-1) soil) were observed only under warm and wet conditions. T
      RFLP analyses of bacterial 16S rRNA and nosZ genes revealed small or undetectable
      community changes in response to temperature and water content, suggesting that
      bacterial and denitrifying microbial communities are stable and do not respond
      significantly to seasonal changes in soil conditions. In contrast, archaeal
      microbial community structure was more dynamic and was strongly influenced by
      temperature.

PMID- 18710396
TI  - Cloning and sequencing of the gene for cellobiose 2-epimerase from a ruminal
      strain of Eubacterium cellulosolvens.
AB  - Cellobiose 2-epimerase (CE; EC 5.1.3.11) is known to catalyze the reversible
      epimerization of cellobiose to 4-O-beta-D-glucopyranosyl-D-mannose in
      Ruminococcus albus cells. Here, we report a CE in a ruminal strain of Eubacterium
      cellulosolvens for the first time. The nucleotide sequence of the CE had an ORF
      of 1218 bp (405 amino acids; 46 963.3 Da). The CE from E. cellulosolvens showed
      44-54% identity to N-acyl-D-glucosamine 2-epimerase-like hypothetical proteins in
      the genomes of Coprococcus eutactus, Faecalibacterium prausnitzii, Clostridium
      phytofermentans, Caldicellulosiruptor saccharolyticus, and Eubacterium siraeum.
      Surprisingly, it exhibited only 46% identity to a CE from R. albus. The
      recombinant enzyme expressed in Escherichia coli was purified by two-step
      chromatography. The purified enzyme had a molecular mass of 46.7 kDa and
      exhibited optimal activity at around 35 degrees C and pH 7.0-8.5. In addition to
      cello-oligosaccharides, it converted lactose to epilactose (4-O-beta-D
      galactopyranosyl-D-mannose).

PMID- 18710397
TI  - Diversity of endophytic bacteria from Eucalyptus species seeds and colonization
      of seedlings by Pantoea agglomerans.
AB  - The diversity and beneficial characteristics of endophytic microorganisms have
      been studied in several host plants. However, information regarding naturally
      occurring seed-associated endophytes and vertical transmission among different
      life-history stages of hosts is limited. Endophytic bacteria were isolated from
      seeds and seedlings of 10 Eucalyptus species and two hybrids. The results showed
      that endophytic bacteria, such as Bacillus, Enterococcus, Paenibacillus and
      Methylobacterium, are vertically transferred from seeds to seedlings. In
      addition, the endophytic bacterium Pantoea agglomerans was tagged with the gfp
      gene, inoculated into seeds and further reisolated from seedlings. These results
      suggested a novel approach to change the profile of the plants, where the
      bacterium is a delivery vehicle for desired traits. This is the first report of
      an endophytic bacterial community residing in Eucalyptus seeds and the
      transmission of these bacteria from seeds to seedlings. The bacterial species
      reported in this work have been described as providing benefits to host plants.
      Therefore, we suggest that endophytic bacteria can be transmitted vertically from
      seeds to seedlings, assuring the support of the bacterial community in the host
      plant.

PMID- 18710398
TI  - Carbon metabolism of the moderately acid-tolerant acetogen Clostridium drakei
      isolated from peat.
AB  - A moderately acid-tolerant, malodorous bacterium, strain FP, was isolated from
      peat that had a pore water pH of c. 4.2. The 16S rRNA gene sequence of FP was
      closely related to that of acetogens Clostridium drakei, Clostridium
      scatologenes, and Clostridium carboxidivorans. The DNA-DNA reassociation values
      obtained with DNA from FP and that of these three acetogens approximated 80%,
      64%, and 59%, respectively, indicating that FP was a new strain of C. drakei. FP
      had broad pH and temperature ranges (3.6-7.4 and 5-40 degrees C, respectively),
      and metabolized a wide range of substrates, including cellobiose, glucose,
      xylose, vanillate, ferulate, lactate, propanol, formate, H(2)-CO(2), and CO
      CO(2). Acetate was the primary reduced end product, and substrate/product
      stoichiometries were indicative of acetogenesis at circumneutral pH. Butyrate and
      H(2) became significant products from glucose at low pH. FP tolerated and could
      consume moderate amounts of O(2). These results (1) demonstrate that peat can
      harbor acetogens with a broad substrate range and tolerance to transient exposure
      to O(2), and (2) confirm that C. drakei, the type strain of which was originally
      isolated from an acidic coal mine pond, occurs in moderately acidic habitats.

PMID- 18710399
TI  - Disposition of eslicarbazepine acetate in the mouse after oral administration.
AB  - Eslicarbazepine acetate is a promising antiepileptic drug structurally related to
      carbamazepine and oxcarbazepine, which is in the final phase of clinical
      development. The metabolism of eslicarbazepine acetate is clearly species
      dependent and, in this case, among small laboratory animals, the mouse seems to
      be the most relevant species to humans. Hence, the aim of this study was to
      investigate the plasma, brain and liver disposition of eslicarbazepine acetate in
      mice to better understand its disposition in humans. Adult male CD-1 mice were
      treated orally with a single dose of eslicarbazepine acetate 350 mg/kg. Blood
      samples, brain and liver tissues were taken at 0.25, 0.5, 0.75, 1, 2, 4, 6, 10,
      16 and 24 h post-dose. Plasma and tissue levels of eslicarbazepine acetate and
      its metabolites (S-licarbazepine, R-licarbazepine and oxcarbazepine) were
      assessed by using high-performance liquid chromatography-ultraviolet detection.
      Both eslicarbazepine acetate and R-licarbazepine concentrations were below the
      limit of quantification of the assay in all matrices. Eslicarbazepine acetate was
      rapidly and extensively metabolized to S-licarbazepine (major metabolite), which
      was oxidized to oxcarbazepine to a small extent. The brain/plasma ratios suggest
      that the brain exposure to S-licarbazepine and oxcarbazepine was approximately
      30% of their total systemic exposure. However, S-licarbazepine crossed the blood
      brain barrier (BBB) less efficiently than oxcarbazepine. On the other hand, the
      liver/plasma ratios support the notion that S-licarbazepine undergoes hepatic
      accumulation, whereas oxcarbazepine appears to leave this compartment twice as
      fast as S-licarbazepine. Thus, the diffusion through the BBB is favourable to
      oxcarbazepine and the liver acts like a deposit of the pharmacologically active
      metabolite of eslicarbazepine acetate (S-licarbazepine).

PMID- 18710401
TI  - Maxillary complete denture movement during chewing in  mandibular removable
      partial denture wearers.
AB  - OBJECTIVES: To evaluate the pattern of maxillary complete denture movement during
      chewing for free-end removable partial dentures (RPD) wearers, compared to
      maxillary and mandibular complete denture wearers. MATERIALS AND METHODS:
      Eighteen edentulous participants (group I) and 10 volunteers with bilateral
      posterior edentulous mandibles (group II) comprised the sample. Measures of mean
      denture movement and its variability were obtained by a kinesiographic instrument
      K6-I Diagnostic System, during the mastication of bread and a polysulphide block.
      Data were analysed using two-way ANOVA (alpha = 0.05). RESULTS: Upper movement
      during chewing was significantly lower for group II, regardless of the test food.
      The test food did not influence the vertical or lateral position of the denture
      bases, but more anterior dislocation was found when polysulphide blocks were
      chewed. Group II presented lower intra-individual variability for the vertical
      axis. Vertical displacement was also more precise with bread as a test food.
      CONCLUSION: It can be concluded that mandibular free-end RPD wearers show smaller
      and more precise movements than mandibular complete denture wearers.

PMID- 18710400
TI  - The lipopolysaccharide Parkinson's disease animal model: mechanistic studies and
      drug discovery.
AB  - Research in the last two decades has unveiled an important role for
      neuroinflammation in the degeneration of the nigrostriatal dopaminergic (DA)
      pathway that constitutes the pathological basis of the prevailing movement
      disorder, Parkinson's disease (PD). Neuroinflammation is characterized by the
      activation of brain glial cells, primarily microglia and astrocytes that release
      various soluble factors that include free radicals (reactive oxygen and nitrogen
      species), cytokines, and lipid metabolites. The majority of these glia-derived
      factors are proinflammatory and neurotoxic and are particularly deleterious to
      oxidative damage-vulnerable nigral DA neurons. As a proof of concept, various
      immunologic stimuli have been employed to directly induce glial activation to
      model DA neurodegeneration in PD. The bacterial endotoxin, lipopolysaccharide
      (LPS), has been the most extensively utilized glial activator for the induction
      of inflammatory DA neurodegeneration. In this review, we will summarize the
      various in vitro and in vivo LPS PD models. Furthermore, we will highlight the
      contribution of the LPS PD models to the mechanistic studies of PD pathogenesis
      and the search for neuroprotective agents for the treatment of PD.

PMID- 18710402
TI  - Intracellular concentrations of Ca(2+) modulate the strength of signal and alter
      the outcomes of cytotoxic T-lymphocyte antigen-4 (CD152)-CD80/CD86 interactions
      in CD4(+) T lymphocytes.
AB  - The costimulatory receptors CD28 and cytotoxic T-lymphocyte antigen (CTLA)-4 and
      their ligands, CD80 and CD86, are expressed on T lymphocytes; however, their
      functional roles during T cell-T cell interactions are not well known. The
      consequences of blocking CTLA-4-CD80/CD86 interactions on purified mouse CD4(+) T
      cells were studied in the context of the strength of signal (SOS). CD4(+) T cells
      were activated with phorbol 12-myristate 13-acetate (PMA) and different
      concentrations of a Ca(2+) ionophore, Ionomycin (I), or a sarcoplasmic Ca(2+)
      ATPase inhibitor, Thapsigargin (TG). Increasing concentrations of I or TG
      increased the amount of interleukin (IL)-2, reflecting the conversion of a low to
      a high SOS. During activation with PMA and low amounts of I, intracellular
      concentrations of calcium ([Ca(2+)](i)) were greatly reduced upon CTLA-4
      CD80/CD86 blockade. Further experiments demonstrated that CTLA-4-CD80/CD86
      interactions reduced cell cycling upon activation with PMA and high amounts of I
      or TG (high SOS) but the opposite occurred with PMA and low amounts of I or TG
      (low SOS). These results were confirmed by surface T-cell receptor (TCR)-CD3
      signalling using a low SOS, for example soluble anti-CD3, or a high SOS, for
      example plate-bound anti-CD3. Also, CTLA-4-CD80/CD86 interactions enhanced the
      generation of reactive oxygen species (ROS). Studies with catalase revealed that
      H(2)O(2) was required for IL-2 production and cell cycle progression during
      activation with a low SOS. However, the high amounts of ROS produced during
      activation with a high SOS reduced cell cycle progression. Taken together, these
      results indicate that [Ca(2+)](i) and ROS play important roles in the modulation
      of T-cell responses by CTLA-4-CD80/CD86 interactions.

PMID- 18710403
TI  - Alteration of N-glycosylation in the kidney in a mouse model of systemic lupus
      erythematosus: relative quantification of N-glycans using an isotope-tagging
      method.
AB  - Changes in the glycan structures of some glycoproteins have been observed in
      autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid
      arthritis. A deficiency of alpha-mannosidase II, which is associated with
      branching in N-glycans, has been found to induce SLE-like glomerular nephritis in
      a mouse model. These findings suggest that the alteration of the glycosylation
      has some link with the development of SLE. An analysis of glycan alteration in
      the disordered tissues in SLE may lead to the development of improved diagnostic
      methods and may help to clarify the carbohydrate-related pathogenic mechanism of
      inflammation in SLE. In this study, a comprehensive and differential analysis of
      N-glycans in kidneys from SLE-model mice and control mice was performed by using
      the quantitative glycan profiling method that we have developed previously. In
      this method, a mixture of deuterium-labelled N-glycans from the kidneys of SLE
      model mice and non-labelled N-glycans from kidneys of control mice was analysed
      by liquid chromatography/mass spectrometry. It was revealed that the low
      molecular-mass glycans with simple structures, including agalactobiantennary and
      paucimannose-type oligosaccharides, markedly increased in the SLE-model mouse. On
      the other hand, fucosylated and galactosylated complex type glycans with high
      branching were decreased in the SLE-model mouse. These results suggest that the
      changes occurring in the N-glycan synthesis pathway may cause the aberrant
      glycosylations on not only specific glycoproteins but also on most of the
      glycoproteins in the SLE-model mouse. The changes in glycosylation might be
      involved in autoimmune pathogenesis in the model mouse kidney.

PMID- 18710404
TI  - Co-ordinated expression of lymphoid and myeloid specific transcription factors
      during B-1b cell differentiation into mononuclear phagocytes in vitro.
AB  - We previously demonstrated that B-1b cells can undergo differentiation to acquire
      a mononuclear phagocyte phenotype upon attachment to substrate in vitro. Here we
      followed the expression of surface markers and transcription factors during this
      differentiation. B-1b cells spontaneously express both myeloid and lymphoid
      restricted transcription factors. When induced to differentiate into a phagocyte,
      the lymphoid genes E box protein (E2A), early B-cell factor (EBF), paired box 5
      (Pax5) are down-modulated, while expression of genes related to myeloid
      commitment is sustained. Furthermore, B-1b cell-derived phagocytes (B-1CDPs)
      decrease immunoglobulin M (IgM) expression but retain the expression of the heavy
      chain variable gene VH11 or VH12, an immunoglobulin gene rearrangement
      predominantly expressed by B-1 cells. The maintenance of lymphoid characteristics
      in B-1CDPs characterizes a unique type of phagocyte, not related to monocyte
      derived macrophages.

PMID- 18710405
TI  - Tumour necrosis factor (TNF)-alpha primes murine neutrophils when triggered via
      formyl peptide receptor-related sequence 2, the murine orthologue of human formyl
      peptide receptor-like 1, through a process involving the type I TNF receptor and
      subcellular granule mobilization.
AB  - Neutrophil granulocytes play an important role in innate host defence against
      microbial invasions and they are also the key effector cells in mediating host
      tissue damage. These functions often rely on the production of reactive oxygen
      species (ROS) from the membrane-bound NADPH-oxidase system. The magnitude of ROS
      production varies depending on the state of the cells, i.e. resting or primed.
      Many priming agents as well as potent NADPH-oxidase activators have been
      identified and characterized for human neutrophils. The cytokine tumour necrosis
      factor (TNF)-alpha is one prominent example of a priming agent and the synthetic
      hexapeptide WKYMVm is an agonist that triggers an activation of the NADPH-oxidase
      of human neutrophils through two members of the formyl peptide family of
      receptors, formyl peptide receptor (FPR) and FPR-like 1 (FPRL1). This peptide
      also activates murine neutrophils but the precise receptor involved has not been
      previously characterized. We show in this study that WKYMVm activates stably
      transfected HL60 cells expressing murine formyl peptide receptor-related sequence
      2 (Fpr-rs2) and that activation of murine neutrophils with WKYMVm is blocked by
      an FPRL1-specific antagonist. WKYMVm is thus an agonist for Fpr-rs2 and we
      suggest that this receptor is in fact the mouse orthologue of FPRL1. In addition,
      we show that the WKYMVm response in murine neutrophils can be primed by TNF-alpha
      and this priming process involves mobilization of subcellular granules. The
      results obtained using neutrophils derived from TNF receptor type I (TNFRI)
      deficient animals suggest that TNF-alpha exerts its priming effect via the TNFRI.

PMID- 18710407
TI  - Elucidating the genetics of male infertility: understanding transcriptional and
      translational regulatory networks involved in spermatogenesis.

PMID- 18710406
TI  - Multivesicular bodies in intestinal epithelial cells: responsible for MHC class
      II-restricted antigen processing and origin of exosomes.
AB  - In normal conditions intestinal epithelial cells (IECs) constitutively stimulate
      regulatory CD4(+) T cells. However, in Crohn's disease (CD), this major
      histocompatibility complex (MHC) class II-restricted antigen presentation results
      in stimulation of proinflammatory CD4(+) T cells. We hypothesized that these
      alternative functions might be mediated by differential sorting and processing of
      antigens into distinct MHC II-enriched compartments (MIICs). Accordingly, we
      analysed the endocytic pathways of lumenally applied ovalbumin (OVA) in IECs of
      the jejunum and ileum of wild-type (WT) and TNFDeltaARE/WT mice that develop a CD
      resembling ileitis. Using quantitative reverse transcription polymerase chain
      reaction, we found that messenger RNA levels of interferon-gamma, tumour necrosis
      factor-alpha, interleukin-17 and interleukin-10 were significantly up-regulated
      in the inflamed ileum of TNFDeltaARE/WT mice, confirming CD-like inflammation.
      Fluorescence and immunoelectron microscopy revealed the presence of MHC II and
      invariant chain throughout the late endocytic compartments, with most molecules
      concentrated in the multivesicular bodies (MVB). OVA was targeted into MVB and,
      in contrast to other MIICs, accumulated in these structures within 120 min of
      exposure. The IEC-specific A33 antigen localized to internal vesicles of MVB and
      A33/class II-bearing exosomes were identified in intercellular spaces.
      Remarkably, the expression pattern of MHC II/invariant chain molecules and the
      trafficking of OVA were independent of mucosal inflammation and the specific
      region in the small intestine. MVB seem to be principally responsible for class
      II-associated antigen processing in IECs and to constitute the origin of MHC II
      loaded exosomes. The distinctive functions of IECs in antigen presentation to
      CD4(+) T cells might arise as a result of differential processing within the MVB
      identified here.

PMID- 18710409
TI  - Semen characteristics and inflammatory mediators in infertile men with different
      clinical diagnoses.
AB  - This study was aimed at investigating whether semen characteristics in different
      clinical diagnoses of infertility are associated with PMN elastase, IL-6, IL-8,
      IL-1beta and TNFalpha levels detected in seminal plasma. Sixty-eight patients
      were divided into groups according to their clinical diagnosis: idiopathic
      infertility (group I), varicocele with infections (group II), varicocele (group
      III), infections (group IV), controls (group V). Physical examination and scrotal
      Eco-color Doppler was used to detect the varicocele. Patients with positive
      bacteriological semen analysis were considered as having an infection of the male
      reproductive tract. Samples were examined by light microscopy and transmission
      electron microscopy (TEM). TEM data were quantified with a mathematical formula
      furnishing a fertility index and the percentage of sperm apoptosis, immaturity
      and necrosis. PMN elastase/alpha1-PI complex levels were determined by ELISA and
      IL-6, IL-8, IL-1beta, TNFalpha by Bio-Plex Cytokine assay. Sperm concentration (I
      II: p < 0.005; III-IV: p < 0.0001), motility (I-IV: p < 0.0001) and the fertility
      index (I: p < 0.005; II-IV: p < 0.0001) were significantly lower in the groups
      vs. controls, whereas sperm pathologies, except for apoptosis, were significantly
      higher in group I and apoptosis and necrosis were higher in group III. An
      increase in immaturity (p < 0.005) with a decrease in necrosis (p < 0.005) were
      observed in group III vs. group IV. Significantly higher levels of inflammatory
      mediators were detected in groups III and IV vs. controls. Despite a broad
      relationship among different inflammatory mediators, no correlation was found
      among them and the semen parameters, including indices from TEM analysis. In
      conclusion, patients with idiopathic infertility showed altered semen quality and
      normal levels of inflammatory mediators. Genitourinary infection and varicocele
      induced an inflammatory effect which could play a detrimental role in
      spermatogenesis, revealed by a decrease in sperm motility and the fertility
      index, concomitant with an increase in immaturity mainly in varicocele and
      necrosis in infection.

PMID- 18710410
TI  - Effect of aqueous extract of Bulbine natalensis (Baker) stem on the sexual
      behaviour of male rats.
AB  - The phytochemical constituents of aqueous extract of Bulbine natalensis (Baker)
      stem and its effect on male rat sexual behaviour were evaluated for 7 days.
      Phytochemical screening revealed the presence of saponins, cardiac glycoside,
      tannins, alkaloids and anthraquinones. Administration of the extract at the doses
      of 25 and 50 mg/kg body weight resulted in the significant increase (p < 0.05) in
      mount frequency, intromission frequency, ejaculatory latency, ejaculation
      frequency, serum testosterone and luteinizing hormone concentrations, computed
      indices of sexual behaviour, erection, quick flips, long flips and total penile
      reflexes whereas the mount latency, intromission latency and post-ejaculatory
      interval were significantly decreased (p < 0.05) throughout the experimental
      period. The 100 mg/kg body weight of the extract produced contrasting pattern to
      the lower doses of the extract in all the parameters of sexual behaviour
      monitored throughout the experimental period. The results are indicative of
      prosexual stimulatory potentials of Bulbine natalensis in male rats. The aqueous
      extract of Bulbine natalensis stem at these doses (25 and 50 mg/kg body weight)
      may be used in the management of disorders of desire/libido, premature
      ejaculation and erectile dysfunction in males.

PMID- 18710411
TI  - Hematological features and molecular lesions of hemoglobin gene disorders in
      Taiwanese patients.
AB  - Hemoglobin (Hb) gene disorders are one of the most common inherited diseases in
      Taiwan, which include alpha-thalassemia, beta-thalassemia, and Hb variants. In
      this study, we collected and analyzed mutations found in 930 patients with Hb
      gene disorders except Hb Bart's Hydrops and beta-thalassemia major. The patients
      included 650 cases of alpha-thalassemia, 225 cases of beta-thalassemia, 9 cases
      of alpha-thalassemia combined with beta-thalassemia, and 46 cases of Hb variants
      or Hb variants combined with alpha-thalassemia or beta-thalassemia. The most
      common type of alpha0-thalassemia and alpha++-thalassemia mutations in our study
      were the SEA type deletion and the alpha3.7 deletion, respectively; the most
      common beta-thalassemia mutation was the IVS-2 nt 654 C-->T mutation; and the
      most common Hb variant was the HbE. We compared the relationships between
      genotype and hematological phenotypes of various Hb gene disorders and found that
      different genotypes of alpha0-thalassemia have similar hematological features. In
      conclusion, the results of our study provide data of the complex interaction of
      thalassemias and Hb variants which might be useful for other researchers in this
      field.

PMID- 18710412
TI  - Effect of MMP-1 promoter polymorphisms on GCF MMP-1 levels and outcome of
      periodontal therapy in patients with severe chronic periodontitis.
AB  - AIMS: The aims of this study were to investigate (1) the matrix metalloproteinase
      1 (MMP-1) promoter polymorphisms in severe chronic periodontitis (CP), (2) the
      relationship of periodontal therapy outcome with these genotypes, and (3) the
      gingival crevicular fluid (GCF) MMP-1 levels-MMP-1 genotype correlation. MATERIAL
      AND METHODS: Genomic DNA was obtained from the peripheral blood of 102 patients
      with severe CP and 98 periodontally healthy subjects. MMP-1 -519A/G and -1607
      1G/2G polymorphisms were determined by the polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method. Fifty-eight CP patients received
      non-surgical periodontal therapy and were followed for 6 months. Clinical
      periodontal parameters and GCF samples were collected at baseline and at 6
      months. GCF MMP-1 levels were analysed by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: The distribution of MMP-1 genotypes did not significantly
      differ between the study groups. On the other hand, the -1607 2G allele frequency
      of severe CP patients was higher than that of healthy subjects. MMP-1 -519G
      allele carriers had higher GCF MMP-1 levels and percentage of sites with 4-6 mm
      clinical attachment level (CAL) compared with AA genotypes after non-surgical
      periodontal therapy (p<0.05). CONCLUSIONS: These data suggest that the -1607 2G
      polymorphic allele of the MMP-1 gene could be associated with susceptibility to
      severe CP in the Turkish population. It seems that -519AG and GG genotypes could
      play a role in the outcome of periodontal therapy.

PMID- 18710413
TI  - Low risk of melanoma in patients with atopic dermatitis.
AB  - BACKGROUND: There is a possible association between atopy and cancer based on the
      concept of atopic diseases as a hyper-reactive state of the immune system.
      Melanoma is an immunogenic tumour, and since patients with atopic dermatitis (AD)
      are subjected to local and systemic immunosuppressives, it would be expected to
      find an influence of AD on the melanoma risk. There is a positive correlation
      between the number of naevi and melanoma risk, and children and adults with AD
      have fewer naevi than controls although many patients receive ultraviolet
      treatment. OBJECTIVE: This study aims to investigate the melanoma risk in a
      retrospective cohort of AD patients compared with the population. STUDY DESIGN:
      6280 AD patients born 1935-1979 visited five Dermatology clinics during 1986
      2004. Mean follow-up time was 36.7 years (SD 6.9) corresponding to 230 742 person
      years at risk. The cohort file was linked to the National Cancer register.
      RESULTS: Six AD patients with melanoma were identified, and the Poisson
      regression analysis adjusted for age group, sex and year resulted in an incidence
      rate ratio of 0.49 (95% confidence interval: 0.27-1.35, P = 0.08) for the AD
      group compared with the total population in the region. CONCLUSION: A low risk to
      develop melanoma was found in AD patients. However, the results must be
      interpreted with caution since the small number of expected cases of melanoma
      makes the risk estimate sensitive to chance effects. We hypothesize that
      formation of naevi and progression to melanoma is counteracted by the
      inflammatory process in the skin of AD patients.

PMID- 18710414
TI  - Pregnenolone sulfate induces NMDA receptor dependent release of dopamine from
      synaptic terminals in the striatum.
AB  - Neuromodulators that alter the balance between lower-frequency glutamate-mediated
      excitatory and higher-frequency GABA-mediated inhibitory synaptic transmission
      are likely to participate in core mechanisms for CNS function and may contribute
      to the pathophysiology of neurological disorders such as schizophrenia and
      Alzheimer's disease. Pregnenolone sulfate (PS) modulates both ionotropic
      glutamate and GABA(A) receptor mediated synaptic transmission. The enzymes
      necessary for PS synthesis and degradation are found in brain tissue of several
      species including human and rat, and up to 5 nM PS has been detected in extracts
      of postmortem human brain. Here, we ask whether PS could modulate transmitter
      release from nerve terminals located in the striatum. Superfusion of a
      preparation of striatal nerve terminals comprised of mixed synaptosomes and
      synaptoneurosomes with brief-duration (2 min) pulses of 25 nM PS demonstrates
      that PS increases the release of newly accumulated [3H]dopamine ([3H]DA), but not
      [14C]glutamate or [3H]GABA, whereas pregnenolone is without effect. PS does not
      affect dopamine transporter (DAT) mediated uptake of [3H]DA, demonstrating that
      it specifically affects the transmitter release mechanism. The PS-induced [3H]DA
      release occurs via an NMDA receptor (NMDAR) dependent mechanism as it is blocked
      by D-2-amino-5-phosphonovaleric acid. PS modulates DA release with very high
      potency, significantly increasing [3H]DA release at PS concentrations as low as
      25 pM. This first report of a selective direct enhancement of synaptosomal
      dopamine release by PS at picomolar concentrations via an NMDAR dependent
      mechanism raises the possibility that dopaminergic axon terminals may be a site
      of action for this neurosteroid.

PMID- 18710416
TI  - Involvement of miltefosine-mediated ERK activation in glioma cell apoptosis
      through Fas regulation.
AB  - The anti-neoplastic property of alkyl phospholipids has been tested for the
      treatment of several malignancies. In this study, we evaluated the efficacy of
      miltefosine (Hexadecylphosphocholine--an alkyl phospholipids analogue) on
      glioblastoma multiforme. In this study, we demonstrate that miltefosine-induced
      apoptosis is accompanied by elevated Fas, Fas-associated death domain (FADD)
      expression, caspase-8 activity and the increased distribution of Fas and FADD
      towards lipid raft microdomain to form death inducing signaling complex.
      Treatment with miltefosine resulted in increase in Ras, extracellular signal
      regulated kinase (ERK) and p38MAPK activity. Expression of dominant-negative Ras
      (Ras N17) attenuated miltefosine-mediated apoptosis. Although inhibition of both
      ERK and p38MAPK decreased the pro-apoptotic effects of miltefosine, it was the
      inhibition of ERK and not p38MAPK activation that decreased Fas and FADD
      expression. An ERK-dependent increase in the expression of gammaH2AX-involved in
      response to DNA double-stranded breaks was also observed. Taken together, our
      findings suggest the involvement of ERK activation in miltefosine-induced glioma
      cell apoptosis.

PMID- 18710415
TI  - PPARalpha and PPARgamma effectively protect against HIV-induced inflammatory
      responses in brain endothelial cells.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors which
      down-regulate inflammatory signaling pathways. Therefore, we hypothesized that
      alterations of PPAR functions can contribute to human immunodeficiency virus-1
      (HIV-1)-induced dysfunction of brain endothelial cells. Indeed, treatment with
      HIV-1 transactivator of transcription (Tat) protein decreased PPAR
      transactivation in brain endothelial cells. We next stably over-expressed
      PPARalpha and PPARgamma in a newly developed cell line of human brain endothelial
      cells (hCMEC/D3 cells). Tat-induced up-regulation of inflammatory mediators, such
      as interleukin (IL)-1beta, tumor necrosis factor-alpha, CCL2, and E-selectin were
      markedly attenuated in hCMEC/D3 over-expressing PPARalpha or PPARgamma. These
      results were confirmed in CCL2 and E-selectin promoter activity studies. Similar
      protective effects were observed in hCMEC/D3 after activation of PPARgamma by
      exogenous PPAR agonists (dPGJ(2) and rosiglitazone). PPAR over-expression also
      prevented Tat-induced binding activity and transactivation of nuclear factor
      kappaB. Importantly, increased PPAR activity attenuated induction of IL-1beta,
      tumor necrosis factor-alpha, CCL2, and E-selectin in hCMEC/D3 cells co-cultured
      with HIV-1-infected Jurkat cells. The protective effects of PPAR over-expression
      were reversed by the antagonists of PPARalpha (MK886) or PPARgamma (GW9662). The
      present data suggest that targeting PPAR signaling may provide a novel
      therapeutic approach to attenuate HIV-1-induced local inflammatory responses in
      brain endothelial cells.

PMID- 18710417
TI  - Characterization of urotensin II, distribution of urotensin II, urotensin II
      related peptide and UT receptor mRNAs in mouse: evidence of urotensin II at the
      neuromuscular junction.
AB  - Urotensin II (UII) and UII-related peptide (URP) are paralog neuropeptides whose
      existence and distribution in mouse have not yet been investigated. In this
      study, we showed by HPLC/RIA analysis that the UII-immunoreactive molecule in the
      mouse brain corresponds to a new UII(17) isoform. Moreover, calcium mobilization
      assays indicated that UII(17) and URP were equally potent in stimulating UII
      receptor (UT receptor). Quantitative RT-PCR and in situ hybridization analysis
      revealed that in the CNS UII and URP mRNAs were predominantly expressed in
      brainstem and spinal motoneurons. Besides, they were differentially expressed in
      the medial vestibular nucleus, locus coeruleus and the ventral medulla. In
      periphery, both mRNAs were expressed in skeletal muscle, testis, vagina, stomach,
      and gall bladder, whereas only URP mRNA could be detected in the seminal vesicle,
      heart, colon, and thymus. By contrast, the UT receptor mRNA was widely expressed,
      and notably, very high amounts of transcript occurred in skeletal muscle and
      prostate. In the biceps femoris muscle, UII-like immunoreactivity was shown to
      coexist with synaptophysin in muscle motor end plate regions. Altogether these
      results suggest that (i) UII and URP may have many redundant biological effects,
      especially at the neuromuscular junction; (ii) URP may more specifically
      participate to autonomic, cardiovascular and reproductive functions.

PMID- 18710418
TI  - Different structural requirements for functional ion pore transplantation suggest
      different gating mechanisms of NMDA and kainate receptors.
AB  - Although considerable progress has been made in characterizing the physiological
      function of the high-affinity kainate (KA) receptor subunits KA1 and KA2, no
      homomeric ion channel function has been shown. An ion channel transplantation
      approach was employed in this study to directly test if homomerically expressed
      KA1 and KA2 pore domains are capable of conducting currents. Transplantation of
      the ion pore of KA1 or KA2 into GluR6 generated perfectly functional ion channels
      that allowed characterization of those electrophysiological and pharmacological
      properties that are determined exclusively by the ion pore of KA1 or KA2. This
      demonstrates for the first time that KA1 and KA2 ion pore domains are
      intrinsically capable of conducting ions even in homomeric pore assemblies. NMDA
      receptors, similar to KA1- or KA2-containing receptors, function only as
      heteromeric complexes. They are composed of NR1 and NR2 subunits, which both are
      non-functional when expressed homomerically. In contrast to NR1, the homomeric
      NR2B ion pore failed to translate ligand binding into pore opening when
      transplanted into GluR6. Similarly, heteromeric coexpression of the ion channel
      domains of both NR1 and NR2 inserted into GluR6 failed to produce functional
      channels. Therefore, we conclude that the mechanism underlying the ion channel
      opening in the obligatorily heterotetrameric NMDA receptors differs significantly
      from that in the facultatively heterotetrameric alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionate and KA receptors.

PMID- 18710419
TI  - Critical role of acrolein in secondary injury following ex vivo spinal cord
      trauma.
AB  - The pathophysiology of spinal cord injury (SCI) is characterized by the initial,
      primary injury followed by secondary injury processes in which oxidative stress
      is a critical component. Secondary injury processes not only exacerbate pathology
      at the site of primary injury, but also result in spreading of injuries to the
      adjacent, otherwise healthy tissue. The lipid peroxidation byproduct acrolein has
      been implicated as one potential mediator of secondary injury. To further and
      rigorously elucidate the role of acrolein in secondary injury, a unique ex vivo
      model is utilized to isolate the detrimental effects of mechanical injury from
      toxins such as acrolein that are produced endogenously following SCI. We
      demonstrate that (i) acrolein-Lys adducts are capable of diffusing from
      compressed tissue to adjacent, otherwise uninjured tissue; (ii) secondary injury
      by itself produces significant membrane damage and increased superoxide
      production; and (iii) these injuries are significantly attenuated by the acrolein
      scavenger hydralazine. Furthermore, hydralazine treatment results in
      significantly less membrane damage 2 h following compression injury, but not
      immediately after. These findings support our hypothesis that, following SCI,
      acrolein is increased to pathologic concentrations, contributes significantly to
      secondary injury, and thus represents a novel target for scavenging to promote
      improved recovery.

PMID- 18710420
TI  - Does nasal decongestion improve obstructive sleep apnea?
AB  - Whether nasal congestion promotes obstructive sleep apnea is controversial.
      Therefore, we performed a randomized placebo-controlled cross-over trial on the
      effects of topical nasal decongestion in patients with obstructive sleep apnea
      syndrome (OSA) and nasal congestion. Twelve OSA patients with chronic nasal
      congestion (mean +/- SD age 49.1 +/- 11.1 years, apnea/hypopnea index 32.6 +/-
      24.5/h) were treated with nasal xylometazoline or placebo for 1 week each. At the
      end of treatment periods, polysomnography including monitoring of nasal
      conductance by an unobtrusive technique, vigilance by the OSLER test, and symptom
      scores were assessed. Data from xylometazoline and placebo treatments were
      compared. Mean nocturnal nasal conductance on xylometazoline was significantly
      higher than on placebo (8.6 +/- 5.3 versus 6.3 +/- 5.8 mL s(-1)Pa(-1), P < 0.05)
      but the apnea/hypopnea index was similar (29.3 +/- 32.5/h versus 33.2 +/- 32.8/h,
      P = NS). However, 30-210 min after application of xylometazoline, at the time of
      the maximal pharmacologic effect, the apnea/hypopnea index was slightly reduced
      (27.3 +/- 30.5/h versus 33.2 +/- 33.9/h, P < 0.05). Xylometazoline did not alter
      sleep quality, sleep resistance time (33.6 +/- 8.8 versus 33.4 +/- 10.1 min, P =
      NS) and subjective sleepiness (Epworth score 10.5 +/- 3.8 versus 11.8 +/- 4.4, P
      = NS). The reduced apnea/hypopnea index during maximal nasal decongestion by
      xylometazoline suggests a pathophysiologic link but the efficacy of nasal
      decongestion was not sufficient to provide a clinically substantial improvement
      of OSA.

PMID- 18710422
TI  - Prognostic significance of Bcl-2 and Bax protein expression in the patients with
      oral squamous cell carcinoma.
AB  - BACKGROUND: The aim of this study was to investigate the expression of the
      apoptosis-inhibitory Bcl-2 protein and the apoptosis-promoting Bax protein and to
      identify their association with the clinical parameters and prognosis of the
      patients with oral squamous cell carcinoma (OSCC). METHODS: The expression of Bcl
      2 and Bax proteins was evaluated by immunohistochemical staining in specimens
      from 110 patients with OSCC. Every section was scored according to both the
      percentage of positive staining tumor cells and the staining intensity. The
      Kaplan-Meier test and Cox proportional hazards regression analysis were performed
      to assess the correlation between the protein levels and the long survival rate
      of patients. The association between Bax, Bcl-2 immunoexpression and
      clinicopathologic variables was analyzed with the chi-square test and non
      parametric analysis. The Bcl-2 and Bax immunoexpression in 20 oral mucosa samples
      were also investigated as normal control. RESULTS: The results showed that the 5
      year survival rate was significantly higher in the patients with the ratio of Bcl
      2/Bax <or= 1 than in those with Bcl-2/Bax > 1 (76.79 +/- 6.69% vs. 59.26 +/-
      6.69%, P = 0.0489). Bax immunoreactivity was significantly correlated with
      histological grading and lymph node metastasis. Univariate analysis indicated
      that the ratio of Bcl-2/Bax and lymph node metastasis were two independent
      factors related to the prognosis. CONCLUSION: The ratio of Bcl-2/Bax could be
      used as an effective biomarker to predict the prognosis of OSCC.

PMID- 18710421
TI  - Laser-capture microdissection of oropharyngeal epithelium indicates restriction
      of Epstein-Barr virus receptor/CD21 mRNA to tonsil epithelial cells.
AB  - BACKGROUND: Epstein-Barr virus colonizes the oropharynx of a majority of
      individuals. It infects B lymphocytes and epithelial cells and can contribute to
      the development of both lymphoid and epithelial tumors. The virus uses CD21 for
      attachment to B cells which constitutively express the protein. Infection of
      epithelial cells in vitro is also more efficient if CD21 is available. However,
      its potential contribution to infection in vivo has been difficult to evaluate as
      discrepant results with antibodies have made it difficult to determine which, if
      any, epithelial cells in the oropharynx express CD21. METHODS: To reevaluate CD21
      expression by an alternative method, epithelial cells were isolated by laser
      capture microdissection from formalin-fixed sections of tissues from various
      parts of the oropharynx and mRNA was amplified with primers specific for the
      exons of CD21 which code for the Epstein-Barr virus binding site. RESULTS: CD21
      mRNA was expressed in tonsil epithelium, but not in epithelium from buccal
      mucosa, uvula, soft palate or tongue. CONCLUSIONS: CD21 does not contribute to
      infection of most normal epithelial tissues in the oropharynx, but may contribute
      to infection of epithelial cells in the tonsil, where virus has been demonstrated
      in healthy carriers.

PMID- 18710423
TI  - Extrahepatic metastasis of hepatocellular carcinoma: incidence and risk factors.
AB  - BACKGROUND: Extrahepatic metastasis of hepatocellular carcinoma (HCC) is of
      growing importance as the survival of patients has been improved owing to
      advances in treatments to intrahepatic lesions. METHODS: To elucidate the
      incidence and risk factors of extrahepatic metastasis of HCC, we enrolled 1573
      (1131 treatment-naive and 442 previously treated on referral) patients with HCC
      without extrahepatic tumour spread treated at the authors' department between
      1990 and 2003. Patients received medical treatment including percutaneous
      ablation and transcatheter arterial chemoembolization, and followed by dynamic
      computed tomography (CT) or magnetic resonance imaging (MRI) and tumour markers
      every 3-4 months. Extrahepatic metastasis was diagnosed by plain X-ray, CT, MRI
      and scintigraphy. Clinical parameters at the time of treatment to intrahepatic
      lesions were evaluated as a predictor of subsequent extrahepatic metastasis among
      the 1131 treatment-naive patients by Cox's proportional hazard model. RESULTS:
      During the average observation period of 3.9 years, extrahepatic metastasis was
      diagnosed in 123 in the treatment-naive and 53 in the patients treated
      previously. The incidence rate of extrahepatic metastasis, as detected during the
      lifetime after medical treatment of HCC, was approximately 13% at 5 years.
      Multivariate analysis with Cox proportional hazard model revealed that positivity
      for viral markers, lager tumour diameter, multiple tumour nodules, presence of
      vascular tumour invasion and elevated tumour markers were associated with the
      development of extrahepatic metastasis. CONCLUSION: The incidence of extrahepatic
      metastasis of HCC diagnosed during clinical course was not frequent. Advanced
      intrahepatic lesions, presence of vascular tumour invasion, elevated tumour
      markers and presence of viral hepatitis were risk factors for extrahepatic
      metastasis.

PMID- 18710424
TI  - Increased hepatic expression is a major determinant of serum alanine
      aminotransferase elevation in mice with nonalcoholic steatohepatitis.
AB  - BACKGROUND: Serum alanine aminotransferase (ALT) is a biomarker for hepatitis of
      various aetiologies including fatty liver disease. Increased serum ALT is thought
      to be related to its increased release from dying hepatocytes. AIM: We sought to
      understand the mechanisms by which serum ALT is elevated in a mouse model of
      experimental fatty liver disease where hepatocyte death is minimal. METHODS: To
      induce fatty liver disease, female A/J mice were fed a methionine-choline
      deficient (MCD) diet for up to 12 weeks. Serum and liver ALT expression and
      hepatic inflammation, necrosis and apoptosis were assessed and expressed relative
      to their expressions in control-diet-fed mice. RESULTS: Feeding mice the MCD diet
      produced hepatic steatosis with minimal hepatic inflammation or necrosis. Liver
      cell apoptosis was not significantly increased by MCD diet treatment. Conversely,
      serum ALT activity was approximately four-fold increased at 12 weeks of diet
      treatment, and ALT protein expressions in serum were correspondingly increased:
      ALT1 1.7-fold and ALT2 1.9-fold at 12 weeks. The expressions of ALT1 and ALT2
      protein in liver increased over 2-12 weeks of MCD treatment. At 12 weeks, liver
      ALT1 protein was 2.27+/-0.31-fold increased and ALT2 protein 4.72+/-0.48-fold
      increased relative to their expressions in the mice fed a diet replete with
      methionine and choline. Liver ALT mRNA expressions were correspondingly
      increased: ALT1 mRNA 2.58-fold and ALT2 mRNA 4.97-fold at 12 weeks. Linear
      regression analysis showed a strong correlation between serum and liver tissue
      expressions for both ALT1 and ALT2. CONCLUSIONS: These findings suggest that
      induction of hepatic expression significantly contributes to increased serum ALT
      in this model of experimental fatty liver disease, whereas cell death appears not
      to.

PMID- 18710425
TI  - Viral suppression correlates with dendritic cell restoration in chronic hepatitis
      B patients with autologous cytokine-induced killer cell transfusion.
AB  - BACKGROUND: Myeloid and plasmacytoid dendritic cells (mDCs, pDCs) are
      functionally impaired in patients with chronic hepatitis B (CHB). Adoptive
      immunotherapy can suppress hepatitis B virus (HBV) replication in CHB patients,
      but whether it can restore the functionality of mDCs and pDCs remains unknown.
      METHODS: Autologous cytokine-induced killer (CIK) cells obtained from 14 CHB
      patients were transfused back to patients, case by case, to observe the effect of
      CIK-cell treatment on the frequency and functionality of mDCs and pDCs in CHB
      patients during a 24-week follow-up investigation. RESULTS: Seven virological
      responders exhibited a sustained decrease in HBV load after CIK-cell transfusion;
      another seven non-virological responders showed only sustained high levels of HBV
      load during the 24-week period following CIK-cell transfusion. The rate of
      hepatitis B e antigen loss or seroconversion was also higher in virological
      responders than in non-virological responders. Importantly, we found that the
      frequency and cytokine-producing capacity of mDCs and pDCs increased
      significantly in virological responders, but not in non-virological responders.
      In addition, these patients exhibited a close correlation between restoration DC
      subsets and a decrease in HBV DNA load, rather than a change in the alanine
      aminotransferase level. CONCLUSION: Cytokine-induced killer-cell treatment
      reduced HBV DNA load in some CHB patients; the efficiency at least partially
      correlates with the restoration of frequency and functionality of mDCs and pDCs.

PMID- 18710426
TI  - Disease progression and the risk factor analysis for chronic hepatitis C.
AB  - BACKGROUND/AIMS: The present study aimed to assess the incidence of advanced
      cirrhotic complications and to identify the risk factors associated with such
      complications in chronic hepatitis C. METHODS: The data of 1137 chronic hepatitis
      C patients were retrospectively reviewed. We analysed the incidence rate and risk
      factors for 'disease progression', as defined by the occurrence of an increase of
      at least 2 points in the Child-Pugh score, oesophageal/gastric variceal bleeding,
      spontaneous bacterial peritonitis, hepatic encephalopathy, death related to liver
      disease or development of hepatocellular carcinoma (HCC). RESULTS: Of the 1137
      patients enrolled for analysis, 490 patients received antiviral treatment. The
      overall annual incidence rate of disease progression was 0.8 and 3.7% for
      patients with and without antihepatitis C virus (anti-HCV) therapy respectively.
      The development of HCC was the most common cause of disease progression. In
      patients with anti-HCV therapy, treatment response, platelet level and aspartate
      aminotranferase:platelet ratio index (APRI) were independent factors associated
      with disease progression. For those without anti-HCV therapy, older age, male
      sex, diabetes, platelet level and APRI were independent factors for disease
      progression. APRI was strongest predictor for disease progression. CONCLUSIONS:
      The present study demonstrated that the development of HCC was the most common
      cause of disease progression, and we also identified the risk factors associated
      with disease progression. Thus, patients at such risks need close monitoring for
      disease progression, and especially for detecting HCC. Moreover, the active
      application of antiviral therapy and efforts to improve the antiviral response
      are required.

PMID- 18710427
TI  - Hepatic steatosis in patients with chronic hepatitis C virus genotype 2 or 3 does
      not affect viral response in patients treated with peginterferon alpha-2a (40KD)
      (PEGASYS) plus ribavirin (COPEGUS) for 16 or 24 weeks.
AB  - BACKGROUND: Hepatic steatosis is common in patients infected with hepatitis C
      virus (HCV). The effect of steatosis on anti-HCV therapy efficacy is unclear.
      METHODS: We studied host and viral factors associated with steatosis and the
      effect of steatosis on treatment efficacy using the database of a large
      prospective trial in patients with HCV genotypes 2 and 3. RESULTS: Out of 885
      patients assessed for steatosis, a total of 614 patients or 69% had steatosis.
      Patients with genotype 3 were more likely to have steatosis than those with
      genotype 2 (79 vs. 59%, P<0.001). Using the logistic regression model, steatosis
      was associated with genotype 3 (P<0.0001), older age (P=0.0025), heavier weight
      (P<0.0001), higher HCV RNA (P<0.0001), and higher ALT levels (P=0.015). By
      univariate analysis, steatosis was associated with lower sustained virological
      response (SVR) in patients with genotype 3, but not in patients with genotype 2.
      When all factors associated with steatosis and SVR were evaluated by logistic
      regression analysis; genotype, age, bodyweight, histological diagnosis, ALT
      quotient, baseline HCV RNA and treatment duration were associated with the
      probability of SVR, but gender, race and steatosis were not. Further analysis
      showed that steatosis remained a non-significant factor while baseline viral load
      was significantly associated with the probability of an SVR. CONCLUSIONS:
      Steatosis did not influence the efficacy of treatment in our study population.
      Baseline viral load is a confounding factor, particularly in patients infected
      with genotype 3 and once baseline viral load was accounted for, the association
      between steatosis and SVR was not relevant.

PMID- 18710428
TI  - Phosphorylation of extracellular signal-regulated kinase 1/2, p38 mitogen
      activated protein kinase and nuclear translocation of nuclear factor-kappaB are
      involved in upregulation of matrix metalloproteinase-9 by tumour necrosis factor
      alpha.
AB  - BACKGROUND: Upregulation of matrix metalloproteinase-9 (MMP-9) induced by tumour
      necrosis factor-alpha (TNF-alpha) is reportedly involved in a variety of non
      neoplastic and neoplastic diseases. In this study, we examined which signalling
      pathways are involved in TNF-alpha-induced MMP-9 upregulation in
      cholangiocarcinoma (CC). METHODS: We used two CC cell lines: HuCCT-1 and CCKS-1.
      RESULTS: In an ex vivo study using HuCCT-1 and CCKS-1 cells, TNF-alpha treatment
      induced MMP-9 production and activation via interaction with TNF receptor-1 (TNF
      R1) but not with TNF receptor-2 (TNF-R2), shown by zymography, and increased MMP
      9 promoter activity (luciferase assay). As for the signalling pathway, TNF-alpha
      stimulation led to the phosphorylation of extracellular signal-regulated kinase
      1/2 (Erk1/2) and p38 mitogen-activated protein kinase (p38MAPK) and translocation
      of nuclear factor kappaB (NF-kappaB) (p65) into the nuclei. Inhibition studies
      using SB203580 (inhibitor of p38MAPK), U0126 (inhibitor of mitogen-activated or
      extracellular signal-regulated protein kinase 1/2) and MG132 (inhibitor of NF
      kappaB) showed that the phosphorylation of Erk1/2 and p38MAPK with activation of
      NF-kappaB was closely related to MMP-9 upregulation in both cell lines.
      CONCLUSION: These data suggest that TNF-alpha/TNF-R1 interaction leads to the
      phosphorylation of Erk1/2 and p38MAPK and nuclear translocation of NF-kappaB,
      which is closely associated with the production and activation of MMP-9 in
      cultured CC cells of HuCTT-1 and CCKS-1. Upregulation of MMP-9 with NF-kappaB
      activation may be involved in the tumour invasion of CC.

PMID- 18710429
TI  - Neuropsychological impairment in severe acute viral hepatitis is due to minimal
      hepatic encephalopathy.
AB  - BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) in patients with liver
      cirrhosis may have prognostic significance with regard to the development of
      clinical hepatic encephalopathy (HE) and deterioration in patient quality of
      life. Its prevalence in acute viral hepatitis (AVH) is not known. PATIENTS AND
      METHODS: Consecutive 20 AVH patients (age, 29.9+/-7.9 years; M:F 18:2, hepatitis
      A:B:E: 2:16:2) without overt encephalopathy were evaluated for MHE and followed
      up. All patients underwent number connection tests - A and B, figure connection
      tests - A and B, digit symbol test and object assembly test and critical flicker
      frequency (CFF) at baseline and after the resolution of icterus. MHE was
      diagnosed if two or more psychometric tests were abnormal. RESULTS: Prevalence of
      MHE (n=5) was 25%, which resolved on follow-up during the anicteric resolution
      phase. Five (25%) patients had greater than two abnormal psychometry tests and
      four (20%) had CFF <38 Hz. CFF alone had sensitivity and specificity of 80 and
      100%, respectively, in the diagnosis of MHE. There was significant difference in
      the performance of CFF during the icteric and resolution phase of AVH (40.6+/-3.4
      vs 41.8+/-2.1 Hz, P=0.04). Arterial ammonia level were higher in patients with
      MHE compared with patients without MHE (88.2+/-23.5 vs 53.8+/-10.9 micromol/L,
      P=0.001). On univariate analysis fasting ammonia level at baseline was
      significantly associated with all the psychometric tests (P=0.001). None of the
      patients developed HE either in MHE group or in those who did not had MHE at
      baseline. CONCLUSIONS: MHE occurs in 25% of patients with AVH and resolves on
      follow up with recovery of AVH. Raised arterial ammonia during the icteric phase
      is associated with development of MHE.

PMID- 18710430
TI  - Hepatitis C virus infection enhances insulin resistance induced by visceral fat
      accumulation.
AB  - BACKGROUND/AIMS: To clarify the impact of visceral obesity on hepatitis C virus
      (HCV)-infected patients, we examined the relationship between insulin resistance
      development and visceral fat accumulation. METHODS: We analyzed 87 HCV-infected
      patients with mild fibrosis (stage 1 or 2) in comparison with 125 sex- and age
      matched patients with non-alcoholic fatty liver disease (NAFLD). The degree of
      visceral fat area (VFA; cm(2)) at the umbilical level was measured by abdominal
      computed tomography and divided into two grades: no visceral obesity, VFA<100 and
      visceral obesity, VFA>/=100. Insulin resistance was evaluated by homeostasis
      model assessment of insulin resistance (HOMA-IR) and the quantitative insulin
      sensitivity check index (QUICKI). Pancreatic beta-cell function was evaluated by
      homeostasis model assessment of beta-cell function (HOMA-beta). Serum soluble
      tumour necrosis factor (TNF)-receptors 1 and 2 and adiponectin were measured.
      RESULTS: Insulin resistance evaluated by HOMA-IR and QUICKI was correlated with
      visceral fat accumulation, and was higher in HCV patients than in NAFLD patients
      with visceral obesity. HOMA-beta was higher in HCV patients than in NAFLD
      patients for each VFA grade. Serum-soluble TNF-receptors 1 and 2 were higher in
      HCV patients than in NAFLD patients with visceral obesity. CONCLUSIONS: Hepatitis
      C virus infection is a risk factor for development of insulin resistance,
      particularly in patients with visceral obesity.

PMID- 18710431
TI  - Repression of small toxic protein synthesis by the Sib and OhsC small RNAs.
AB  - The sequences encoding the QUAD1 RNAs were initially identified as four repeats
      in Escherichia coli. These repeats, herein renamed SIB, are conserved in closely
      related bacteria, although the number of repeats varies. All five Sib RNAs in E.
      coli MG1655 are expressed, and no phenotype was observed for a five-sib deletion
      strain. However, a phenotype reminiscent of plasmid addiction was observed for
      overexpression of the Sib RNAs, and further examination of the SIB repeat
      sequences revealed conserved open reading frames encoding highly hydrophobic 18-
      to 19-amino-acid proteins (Ibs) opposite each sib gene. The Ibs proteins were
      found to be toxic when overexpressed and this toxicity could be prevented by
      coexpression of the corresponding Sib RNA. Two other RNAs encoded divergently in
      the yfhL-acpS intergenic region were similarly found to encode a small
      hydrophobic protein (ShoB) and an antisense RNA regulator (OhsC). Overexpression
      of both IbsC and ShoB led to immediate changes in membrane potential suggesting
      both proteins affect the cell envelope. Whole genome expression analysis showed
      that overexpression of IbsC and ShoB, as well as the small hydrophobic LdrD and
      TisB proteins, has both overlapping and unique consequences for the cell.

PMID- 18710432
TI  - Prevalence of self-perceived allergic diseases and risk factors in Italian
      adolescents.
AB  - The aim of the study was to assess the symptoms prevalence of allergic diseases
      in a population of 11-15 yr old schoolchildren, to evaluate the associations
      between asthma and other symptoms and identify risk factors for asthma, rhinitis
      and eczema syndromes. A sample of 481 students was studied using an International
      Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Prevalence of
      different kind of self-reported symptoms was calculated. Using a logistic
      regression approach, we tried to identify risk factors for three syndromes -
      rhinitis, eczema and asthma. The highest and the lowest prevalence rates of self
      reported symptoms were recorded for rhinitis (43.6%) and for eczema (8.1%),
      respectively. The prevalence of asthma was 15.7%. Univariate analysis showed a
      mutual association between wheeze and rhinitis symptoms. Multivariate logistic
      regression model for eczema syndrome revealed female gender as a significant risk
      factor. The polytomic logistic multivariate regression revealed female gender and
      family history of allergy as significant risk factors for rhinitis syndrome only,
      and maternal smoking and familial allergy for rhinitis and asthma together. In
      particular, familial allergy yields a 400% higher chance of developing asthma and
      rhinitis together. The synergistic effect of familial allergy on rhinitis and
      asthma syndromes suggests the implementation of preventive measures in children
      with family history of these diseases.

PMID- 18710433
TI  - The change in ghrelin and obestatin levels in obese children after weight
      reduction.
AB  - AIM: To investigate the role of ghrelin and obestatin in obesity mechanisms.
      METHODS: A total of 88 obese children and 25 normal children were enrolled.
      Moreover, 46 obese children took part in a summer camp for weight reduction.
      Fasting ghrelin, obestatin and other biochemical parameters were measured in all
      subjects and re-measured in 45 obese children finishing the camp. RESULTS: The
      ghrelin levels in the control and obese groups were 67.26 +/- 23.41 pmol/L and
      56.53 +/- 15.97 pmol/L with a significant difference (p = 0.039), while the
      obestatin levels (89.41 +/- 23.63 vs. 83.13 +/- 17.21 pmol/L) were not
      significantly different (p = 0.083). The ghrelin/obestatin ratio in the controls
      was significantly higher than that in the obese group (p = 0.014). In the latter,
      fasting insulin and alanine aminotransferase were independent factors for
      ghrelin; fasting insulin, weight and gender were independent factors for
      obestatin and alanine aminotransferase was an independent factor for
      ghrelin/obestatin. Moreover, ghrelin, obestatin and ghrelin/obestatin increased
      after weight reduction (p < 0.05, respectively), and the increment in ghrelin and
      obestatin was associated with a decrement in insulin resistance. CONCLUSION:
      These data suggest that ghrelin, obestatin and/or the ghrelin/obestatin ratio are
      associated with obesity in childhood.

PMID- 18710434
TI  - Correlations between welfare initiatives and breastfeeding rates: a 10-year
      follow-up study.
AB  - AIM: To evaluate the prevalence of full breastfeeding during the first 6 months
      of age and to discover if training programs for health caregivers and welfare
      initiatives at the community level could improve breastfeeding rates. METHODS:
      Newborn babies with gestational age > or =36 weeks and birth weight > or =2500 g,
      discharged from the hospital within the first week of life, without any
      underlying pathologies, were enrolled in 3-month long sample periods between 1997
      and 2006. A questionnaire was distributed to the mothers, to be completed and
      submitted before hospital discharge. Data were collected from phone interviews at
      1, 3 and 6 months. RESULTS: Full breastfeeding rates at hospital discharge showed
      an oscillation between 69.9% and 87%. The rate decreased in the following months
      and reached very low levels at 6 months of age (< 24%), with the exception of the
      last sample period in 2006 (44.9%). CONCLUSION: A simple questionnaire, combined
      with standardized phone interviews, can be easily reproduced and may be used as
      an indicator for quality of neonatal care at hospital nurseries. A social and
      cultural change of the whole community towards breastfeeding promotion will
      result in increasing breastfeeding rates.

PMID- 18710435
TI  - Medication errors in a neonatal intensive care unit. Influence of observation on
      the error rate.
AB  - AIM: To study if medication error rate decreased as a consequence of a simple
      observation process of registering its occurrence. METHODS: Prescription and
      transcription processes were prospectively registered along two different period
      of time in a level III regional Neonatal Intensive Care Unit: a pilot phase,
      aimed to know the baseline drug error rate and a phase I, a pre-intervention
      phase, both part of a study designed to determinate the effect of a preventive
      strategy in drug error rate. Random drug prescriptions by physicians and their
      transcriptions by nurses were reviewed and registered by a hospital pharmacist. A
      drug error episode was registered if dosage, units, route and administration
      interval were incorrect, illegible or not indicated. RESULTS: A significant
      reduction in the prescription error rate from 32.8% in the pilot phase to 19.2%
      in the pre-intervention study phase was observed (p< 0.001). Rates of incorrect
      dosing (13.6% vs. 5%) and lack of dose specification in the medical prescriptions
      (3.3% vs. 0.5%) dropped significantly but transcription errors did not.
      CONCLUSION: The presence of a person reviewing and registering the drug records
      apparently had by itself a substantial positive effect on the overall drug error
      rate. This phenomenon known as the Hawthorne effect should be taken in
      consideration when evaluating the efficacy of any preventive intervention aimed
      at improving patient safety.

PMID- 18710436
TI  - Clinical trial: gluten microchallenge with wheat-based starch hydrolysates in
      coeliac disease patients - a randomized, double-blind, placebo-controlled study
      to evaluate safety.
AB  - BACKGROUND: Wheat-based starch hydrolysates such as glucose syrups, dextrose and
      maltodextrins are found in more than 50% of European processed food. These
      products contain low amounts of residual gluten and it has been questioned
      whether they are safe for coeliac disease patients. AIM: To investigate whether
      coeliac disease patients can safely consume wheat-based starch hydrolysate
      products. METHODS: This randomized, double-blind, placebo-controlled, prospective
      follow-up study involved 90 coeliac disease patients in remission randomized to
      consume glucose syrups, maltodextrins or placebo for 24 weeks. Small bowel
      mucosal morphology and inflammation, symptoms, coeliac serology and malabsorption
      laboratory data were evaluated at baseline and at the end of the study. RESULTS:
      Daily ingestion of wheat-based starch hydrolysates, glucose syrups and
      maltodextrins, had no deleterious effect on small-bowel mucosal villous
      architecture or inflammation in coeliac disease patients when compared to the
      placebo group. Neither were there any significant differences in gastrointestinal
      symptoms, serology or malabsorption parameters after 24 weeks. CONCLUSIONS: Wheat
      based starch hydrolysates, glucose syrups and maltodextrins did not have harmful
      effect on coeliac disease patients. Coeliac patients can thus safely continue to
      consume these products.

PMID- 18710437
TI  - The developmental basis of skeletal cell differentiation and the molecular basis
      of major skeletal defects.
AB  - Vertebrate skeletal differentiation retains elements from simpler phyla, and
      reflects the differentiation of supporting tissues programmed by primary
      embryonic development. This developmental scheme is driven by homeotic genes
      expressed in sequence, with subdivision of skeletal primordia driven by a
      combination of seven transmembrane-pass receptors responding to Wnt-family
      signals, and by bone morphogenetic family signals that define borders of
      individual bones. In sea-dwelling vertebrates, an essentially complete form of
      the skeleton adapted by the land-living vertebrates develops in cartilage, based
      on type II collagen and hydrophilic proteoglycans. In bony fishes, this skeleton
      is mineralized to form a solid bony skeleton. In the land-living vertebrates,
      most of the skeleton is replaced by an advanced vascular mineralized skeleton
      based on type I collagen, which reduces skeletal mass while facilitating use of
      skeletal mineral for metabolic homeostasis. Regulation of the mammalian skeleton,
      in this context, reflects practical adaptations to the needs for life on land
      that are related to ancestral developmental signals. This regulation includes
      central nervous system regulation that integrates bone turnover with overall
      metabolism. Recent work on skeletal development, in addition, demonstrates
      molecular mechanisms that cause developmental bone diseases.

PMID- 18710438
TI  - The oncological results of laparoscopic nephroureterectomy for upper urinary
      tract transitional cell cancer are equal to those of open nephroureterectomy.
AB  - OBJECTIVE: To compare the overall, tumour-specific, recurrence-free, and
      progression- free survival of patients with upper urinary tract transitional cell
      carcinoma (UUT-TCC) treated with laparoscopic nephroureterectomy (LNU) or
      standard open NU (ONU). PATIENTS AND METHODS: Clinical, pathological and follow
      up data were analysed for 43 LNUs and 59 ONUs performed at our institution from
      1999 to 2006. In LNU the kidney was removed laparoscopically as in radical
      nephrectomy, but without transecting the ureter. The specimen was then removed
      intact with the entire ureter and a bladder cuff through a nonmuscle-splitting
      supra-inguinal incision. ONU was performed through separate intercostal and supra
      inguinal incisions with the entire specimen being removed intact with a bladder
      cuff through the latter. RESULTS: The mean (SD) follow-up was 41 (20) months for
      LNU and 41 (29) for ONU. Pathological staging was: pTa 26% vs 20%, pT1 21% vs
      27%, pT2 12% vs 17%, pT3 42% vs 34% for LNU and ONU, respectively. In all, seven
      vs six patients had positive nodes on final histology. Recurrent tumours in the
      bladder were detected in 26% of patients after LNU and in 27% after ONU after the
      mean follow-up. There were no local recurrences after LNU but there was local
      recurrence in six patients after ONU. There were no port-site metastases during
      the follow-up. Five LNU patients and seven ONU patients developed distant or
      lymph node metastasis. The actuarial 5-year tumour free-survival rate was 79% in
      the LNU group vs 76% in the ONU group (P = 0.82). The actuarial disease-specific
      survival at 5-years was 85% for LNU and 80% for ONU patients (P = 0.62). The
      surgical approach did not influence recurrence or survival. CONCLUSION:
      Oncological results of LNU and ONU are comparable. The lower morbidity of LNU
      offers advantages for the patient.

PMID- 18710439
TI  - Rolipram, a specific type-4 phosphodiesterase inhibitor, inhibits
      cyclophosphamide-induced haemorrhagic cystitis in rats.
AB  - OBJECTIVE: To investigate the protective roles of type 4 phosphodiesterase (PDE4)
      inhibitor in cyclophosphamide (CYP)-induced haemorrhagic cystitis, as the PDE4
      inhibitor has anti-inflammatory effects but its characterization is still unknown
      in urinary tract diseases. MATERIALS AND METHODS: In female Sprague-Dawley rats,
      CYP was administered intraperitoneally and bladders were harvested 24 h after CYP
      injection. In another group, rolipram as a PDE4 inhibitor was administered before
      CYP treatment. The effects and mechanisms of CYP with/without rolipram
      pretreatment were evaluated by microscopic features, bladder wet weight,
      myeloperoxidase (MPO) activity, nitric oxide (NO)-metabolite production and
      expression levels of inflammation-related genes. RESULTS: CYP injection resulted
      in severe cystitis. Pretreatment with rolipram significantly reduced the increase
      in bladder wet weight and MPO activity, and ameliorated histological inflammatory
      changes caused by CYP. The levels of inflammation-related transcripts including
      inducible NO synthase (iNOS), interleukin-1beta and tumour necrosis factor-alpha,
      induced by CYP, were down-regulated significantly by pretreatment with rolipram.
      Also, rolipram reduced the NO-metabolite production and iNOS protein expression
      in the immunohistochemical examination. CONCLUSION: These results indicate that
      rolipram can attenuate the development of CYP-induced cystitis in rats by
      suppressing cytokine production and iNOS induction. Thus, treatment with PDE4
      inhibitor has potential clinical implications of the prevention of bladder
      inflammatory diseases.

PMID- 18710440
TI  - Contemporary imaging of patients with a renal mass: does size on computed
      tomography equal pathological size?
AB  - OBJECTIVE: To evaluate the difference between radiographic size on computed
      tomography (CT) and the pathological size of renal tumours, in contemporary
      patients. PATIENTS AND METHODS: We retrospectively reviewed the records of 521
      patients undergoing surgical resection of a renal mass between 2000 and 2007, who
      had tumour sizes recorded from both preoperative CT and pathological evaluation
      of the tumour specimen. Data on histological tumour type were also extracted. The
      paired Student's t-test was used to compare the mean radiographic size as
      measured on CT with the mean pathological size, with P < 0.05 considered to
      indicate statistical significance. RESULTS: For all patients, the mean
      radiographic size and mean pathological size was 4.79 and 4.69 cm, respectively
      (P = 0.02). Therefore, on average, radiographic size overestimated pathological
      size by 1 mm. In patients with a tumour of 4-7 cm, radiographic size
      overestimated pathological size by 0.21 cm (P = 0.007). However, there was no
      significant difference in patients with a tumour of <4 cm or >7 cm. CONCLUSIONS:
      Using contemporary patients, there was a statistically significant overestimation
      of renal tumour sizes by CT compared with the pathological assessment. However,
      the overall difference between radiographic and pathological tumour size was 1
      mm, suggesting that CT provides an accurate method with which to estimate renal
      tumour size.

PMID- 18710441
TI  - Unilateral vs bilateral sacral neuromodulation in pigs with formalin-induced
      detrusor hyperactivity.
AB  - OBJECTIVE: To investigate the efficacy of unilateral vs bilateral sacral
      neuromodulation (SNM) under standard experimental conditions by stimulating the
      dorsal sacral roots in pigs with formalin-induced detrusor hyperactivity.
      MATERIALS AND METHODS: After lumbosacral laminectomy in eight alpha-chloralose
      anaesthetized Gottinger mini-pigs, the dorsal roots of the nerve S3 were inserted
      into separate compartments of a size-modified Brindley electrode. Detrusor
      hyperactivity was induced by intravesical instillation of a 0.25% formalin
      solution. Stimulation of the separated dorsal roots was performed on the
      unilateral right, respectively, the unilateral left side, as well as bilaterally
      and with stimulation off-phases in a randomized pattern. A biphasic rectangular
      signal (impulse 200 micros, 20 Hz, 2.0 V) was used for SNM. The bladder pressure
      values were registered on a urodynamic unit and evaluated as contractions and
      amplitudes per minute. RESULTS: During unilateral stimulation, the mean (sem)
      number of contractions was reduced significantly from 4.73 (0.66) to 2.73 (0.62).
      The amplitude was also reduced significantly from 12.86 (1.23) to 8.32 (0.66). By
      contrast, bilateral stimulation lowered the mean (sem) number of overactive
      detrusor contractions to 1.08 (1.02) and the amplitude to 3.08 (2.42), which are
      highly significant reductions. CONCLUSION: In this porcine model, bilateral
      neurostimulation was a more effective method of SNM than unilateral stimulation.
      We assume that this is due to the additive effect of stimulating both sides, as
      well as the greater chance of stimulating the relevant dorsal roots of the sacral
      nerve fibres. By contrast, unilateral neuromodulation may be only partially
      effective by not being capable of influencing the entire bladder, or possibly by
      allowing new formation of neuronal pathophysiological pathways.

PMID- 18710442
TI  - Nephrectomy improves the survival of patients with locally advanced renal cell
      carcinoma.
AB  - OBJECTIVES: To examine the cancer-specific survival of patients treated with
      nephrectomy and compared it to that of patients managed without surgery. PATIENTS
      AND METHODS: Of 43,143 patients with renal cell carcinoma (RCC) identified in the
      1988-2004 Surveillance, Epidemiology and End Results database, 7068 had locally
      advanced RCC and with no distant metastasis. These patients had a nephrectomy
      (6786, 96.0%) or no surgical therapy (282, 4.0%). Multivariable Cox regression
      models, and matched and unmatched Kaplan-Meier survival analyses, were used to
      compare the effect of nephrectomy vs non-surgical therapy on cancer-specific
      survival. Also, competing-risks regression models adjusted for the effect of
      other-cause mortality. Covariates and matching variables consisted of age,
      gender, tumour size and year of diagnosis. RESULTS: The 1-, 2-, 5- and 10-year
      cancer-specific survival of patients who had nephrectomy was 88.9%, 88.1%, 68.6%
      and 57.5%, vs 44.8%, 30.6%, 14.5% and 10.6% for non-surgical therapy. In
      multivariable analyses, relative to nephrectomy, non-surgical therapy was
      associated with a 5.8-fold higher rate of cancer-specific mortality (P < 0.001).
      Non-surgical therapy was also associated with a 5.1-fold higher rate of cancer
      specific mortality in matched analyses (P < 0.001). Finally, competing-risks
      regression confirmed the statistical significance of the variable defining
      treatment type (nephrectomy vs non-surgical therapy) in multivariable and matched
      analyses (P < 0.001). CONCLUSION: Relative to non-surgical treatment, nephrectomy
      improves the cancer-specific survival of patients with locally advanced RCC; our
      findings await prospective confirmation.

PMID- 18710443
TI  - Holmium laser prostatic resection for patients presenting with acute urinary
      retention.
AB  - OBJECTIVE: To compare the outcomes of patients presenting with and without acute
      urinary retention (AUR) who were treated with 100-W holmium laser resection of
      the prostate (HoLRP), as laser therapies, including HoLRP, have been used for
      treating lower urinary tract symptoms secondary to benign prostatic hyperplasia
      (BPH), but the effectiveness of HoLRP for patients with AUR has not been fully
      elucidated. PATIENTS AND METHODS: The medical records of 87 patients who had
      HoLRP were reviewed, and prospective questionnaires aimed at determining
      patients' American Urologic Association Symptom Index (AUA-SI) and Quality-of
      Life (QoL) scores and medication usage were also obtained. Statistical analyses
      were used to compare the clinical characteristics and outcomes between patients
      with and with no AUR for up to 2 years after HoLRP. RESULTS: All patients had the
      catheter removed successfully by 1 month after surgery; those presenting with AUR
      tended to have a greater improvement in clinical outcomes than those with no AUR,
      including a mean AUA-SI score decrease by approximately 13 and approximately 8
      points, and a QoL score decrease by approximately 2 and approximately 1.4 points,
      respectively. These decreases were maintained throughout the study period.
      Patients with AUR had significantly greater decreases in their postvoid residual
      urine volume than those with no AUR. Serum prostate-specific antigen levels also
      had a modest but sustained decrease (14%) in both groups. There were no
      significant decreases in the reported use of BPH-related medications after
      surgery in either group. CONCLUSIONS: HoLRP (100 W) is a safe and effective
      surgical therapy for patients presenting with AUR. The present results suggest
      that the short- and long-term outcomes of these patients are similar between men
      presenting with and with no AUR.

PMID- 18710445
TI  - Kidney fusion anomalies revisited: clinical and radiological analysis of 209
      cases of crossed fused ectopia and horseshoe kidney.
AB  - OBJECTIVE: To analyse the morphological appearance of horseshoe kidneys (HKs) and
      crossed fused ectopia (CFE) and to assess the frequency and clinical significance
      of associated anomalies and diseases. PATIENTS AND METHODS: The findings and
      images of 209 patients with fused kidneys (FKs) were reviewed; in all, 244 scans
      from computed tomography (CT), 233 ultrasonograms and 89 micturition cysto
      urethrograms, urograms, magnetic resonance images and angiograms were taken.
      RESULTS: HKs (found in one of 474 abdominal CT scans) and CFEs (found in one of
      3078 CT scans) showed a high variability of vasculature that could not be
      classified. However, some generalized conclusions were possible about the renal
      vasculature (430 arteries in 103 kidneys). Variants of the most cephalad artery
      of both sides were rare. The second artery on the right had a pre-caval course.
      The origins of vessels located further caudal were more ventral. CFEs were
      anatomically different from HKs with respect to lower position, greater axial
      rotation, smaller pelvic width, more caudal origin, and fewer vessels, but not in
      accompanying anomalies. Severe anomalies or malformations were found in 23% of
      patients, with half of them in the urogenital system. Malformations were found
      considerably more often in children than in adults. There was no increased
      incidence of diseases such as stones or inflammation of the renal pelvis.
      CONCLUSION: Concomitant anomalies and diseases were equally frequent for HK and
      CFE, but less frequent than generally assumed. Individual cases of complex
      anatomical situations require special examination strategies, and CT appears to
      be the most reliable imaging method.

PMID- 18710444
TI  - Association of the ABCG2 C421A polymorphism with prostate cancer risk and
      survival.
AB  - OBJECTIVE: To determine if the C421A single nucleotide polymorphism (SNP) in the
      ATP-binding cassette transporter ABCG2 increases prostate cancer risk or affects
      survival. PATIENTS, SUBJECTS AND METHODS: Numerous studies have suggested that
      dietary, hormonal and environmental factors all play a role in the initiation in
      prostate cancer; among these, the carcinogenic heterocyclic amine 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a known substrate of the ABCG2. A
      SNP of ABCG2, C421A, resulting in a glutamine to lysine change at amino acid 141,
      has been shown to result in decreased function of the protein. Due to the
      expression of ABCG2 in the prostate, together with the purported role of dietary
      carcinogens and steroids in the development and progression of prostate cancer,
      311 individuals were genotyped for the ABCG2 C421A SNP, 170 patients with
      androgen-independent prostate cancer (AIPC) and 141 'healthy' controls. We also
      evaluated the effect of this SNP on the intracellular accumulation of PhIP and
      testosterone in vitro. RESULTS: There were no significant differences in the
      prevalence of prostate cancer based on ABCG2 genetic variation in this
      population. However, survival was significantly longer for individuals with wild
      type ABCG2, as compared with those hetero- or homozygous for the C421A SNP (7.4
      years vs 5.3 years, P = 0.044). Intracellular accumulation of PhIP was 80% higher
      in HEK293 cells transfected with Q141K ABCG2 than in wild-type cells, confirming
      that this SNP decreases transport of PhIP. In contrast, testosterone was not
      transported by either wild-type or variant transfected cells, nor did it act as
      in inhibitor of ABCG2 in subsequent transport assays. CONCLUSION: Increased
      exposure to PhIP may decrease survival, but the ABCG2 C421A polymorphism does not
      appear to increase the risk of prostate cancer.

PMID- 18710446
TI  - Efficacy, tolerability and satisfaction with sildenafil citrate 100-mg titration
      compared with continued 50-mg dose treatment in men with erectile dysfunction.
AB  - OBJECTIVE: To evaluate the efficacy, tolerability, and treatment satisfaction
      after initiating treatment with sildenafil 50 mg and later titrating to 100 mg,
      compared with continuing treatment with sildenafil 50 mg, in men with erectile
      dysfunction (ED). PATIENTS AND METHODS: A multicentre, parallel-group trial was
      conducted in two 4-week periods. In period 1, patients received 50-mg doses of
      sildenafil single-blinded for 4 weeks. In period 2, patients were randomized to
      double-blind, placebo-controlled treatment with sildenafil 50 mg or sildenafil
      100 mg for 4 weeks. All patients were aged >or=18 years with a documented
      clinical diagnosis of ED (score of <or=25 on the International Index of Erectile
      Function, IIEF, Erectile Function, EF, domain), and met the prescribing criteria
      for sildenafil 50 mg and 100 mg. RESULTS: Of 492 enrolled patients (mean age 53
      years, SD 11), 476 (97%) completed period 1 and 473 (96%) completed period 2.
      Patients receiving sildenafil 50 mg in period 1 had an increase in the mean (SD)
      baseline EF domain score from 12.8 (5.2) to 22.5 (6.6) (P < 0.001), and improved
      scores on the Quality of Erection Questionnaire (QEQ) and Sexual Experience
      Questionnaire (SEX-Q). The IIEF EF domain scores were similar in the two groups
      at baseline and randomization. Patients titrated to the 100-mg dose (237 men)
      showed a significantly greater improvement than those who continued on the 50-mg
      dose (240; P < 0.001). There was a significant increase in QEQ and SEX-Q scores
      in patients titrated to sildenafil 100 mg compared with patients continuing at
      sildenafil 50 mg. At either sildenafil dose, headache, flushing and hot flushes
      were the most common adverse events. Neither the frequency nor the severity of
      adverse events increased with titration to sildenafil 100 mg. CONCLUSIONS: After
      initial treatment with sildenafil 50 mg, patients titrated to 100 mg showed
      further increases in efficacy and satisfaction with no increase in the number or
      severity of adverse events than in those remaining on the starting dose.

PMID- 18710447
TI  - Histopathological characteristics of lymph node metastases predict cancer
      specific survival in node-positive prostate cancer.
AB  - OBJECTIVE: To correlate the histopathological characteristics of lymph node
      metastases in prostate cancer with cancer-specific survival (CSS). PATIENTS AND
      METHODS: The histopathological slides from 142 patients who had had a pelvic
      lymph node dissection for node-positive prostate cancer were reviewed. For each
      patient we recorded the number of lymph nodes removed, the number of positive
      nodes, the diameter of the largest metastasis and extranodal extension (ENE). The
      lymph node metastases were graded according to the Gleason system. These
      variables were correlated with CSS. RESULTS: The mean age of the patients was
      62.4 years and the mean preoperative prostate-specific antigen level was 40.2
      ng/mL. The median follow-up was 77.5 months, and the median overall and CSS were
      91 and 112 months, respectively. On univariable analysis the following variables
      correlated with poor CSS: a nodal Gleason score of >7 (hazard ratio 2.4, P <
      0.001), a diameter of the largest metastasis of >3 mm (2.2, P = 0.025), more than
      two lymph node metastases (2.0, P = 0.003), and ENE in more than one lymph node
      (1.9, P = 0.014). Multivariable analysis showed only the nodal Gleason score and
      the diameter of the largest metastasis to be independent predictors of CSS (1.8,
      P = 0.021, and 2.2, P = 0.046, respectively). CONCLUSION: The histopathological
      characteristics of lymph node metastases in prostate cancer have predictive value
      for the clinical outcome. The nodal Gleason score and the diameter of the largest
      metastasis are independent predictors of survival.

PMID- 18710448
TI  - Penile fracture: preoperative evaluation and surgical technique for optimal
      patient outcome.
AB  - OBJECTIVE: To review the preoperative diagnostic evaluation and surgical
      treatment of penile fracture, as the condition is a urological emergency that
      requires immediate surgical exploration and repair. PATIENTS AND METHODS: Between
      January 2003 and October 2007 eight patients presented to the emergency
      department with penile fracture after sexual intercourse. The clinical
      presentation, preoperative evaluation and imaging, surgical technique, and
      postoperative care were assessed to determine the optimal patient outcome.
      RESULTS: Seven of the eight patients were treated surgically and one refused
      surgical intervention. Four cases involved unilateral corporal injury, two
      involved unilateral corporal injury with an associated urethral injury, and one
      involved bilateral corporal injury with an associated urethral injury. Although
      retrograde urethrogram were taken of all three urethral injuries, none of them
      revealed the injury. Diagnostic cavernosography or magnetic resonance imaging
      were not used in any of the patients. No complications occurred in the patients
      treated surgically. CONCLUSIONS: Preoperative imaging should not delay surgical
      repair. If an associated urethral injury is suspected, flexible cystoscopy is
      recommended in the operating room, as opposed to a retrograde urethrogram. A
      subcoronal circumcising incision is recommended to deglove the entire penile
      shaft and have complete access to all three corporal bodies, as well as the
      neurovascular bundle. Saline mixed with indigo carmine can be injected both into
      the corpora cavernosum or corpus spongiosum via the glans penis, after a
      tourniquet is placed at the base of the penis, to evaluate the surgical repair
      and to determine if there are any missed injuries.

PMID- 18710449
TI  - Preventing recurrent urinary tract infections: role of vaccines.

PMID- 18710450
TI  - Effect of firing rate on the performance of shock wave lithotriptors.
AB  - OBJECTIVE: To determine the mechanism that underlies the effect of shock wave
      (SW) rate on the performance of clinical lithotripters. MATERIALS AND METHODS:
      The effect of firing rate on the pressure characteristics of SWs was assessed
      using a fibre-optic probe hydrophone (FOPH 500, RP Acoustics, Leutenbach,
      Germany). Shock waves were fired at slow (5-27 SW/min) and fast (100-120 SW/min)
      rates using a conventional high-pressure lithotriptor (DoLi-50, Dornier MedTech
      America, Inc., Kennesaw, GA, USA), and a new low-pressure lithotriptor (XX-ES, Xi
      Xin Medical Instruments Co. Ltd, Suzhou, PRC). A digital camcorder (HDR-HC3,
      Sony, Japan) was used to record cavitation fields, and an ultrafast multiframe
      high-speed camera (Imacon 200, DRS Data & Imaging Systems, Inc., Oakland, NJ,
      USA) was used to follow the evolution of bubbles throughout the cavitation cycle.
      RESULTS: Firing rate had little effect on the leading positive-pressure phase of
      the SWs with the DoLi lithotriptor. A slight reduction ( approximately 7%) of
      peak positive pressure (P+) was detected only in the very dense cavitation fields
      (approximately 1000 bubbles/cm(3)) generated at the fastest firing rate (120
      SW/min) in nondegassed water. The negative pressure of the SWs, on the other
      hand, was dramatically affected by firing rate. At 120 SW/min the peak negative
      pressure was reduced by approximately 84%, the duration and area of the negative
      pressure component was reduced by approximately 80% and approximately 98%,
      respectively, and the energy density of negative pressure was reduced by >99%.
      Whereas cavitation bubbles proliferated at fast firing rates, HS-camera images
      showed the bubbles that persisted between SWs were very small (<10 microm).
      Similar results were obtained with the XX-ES lithotriptor but only after
      recognizing a rate-dependent charging artefact with that machine. CONCLUSION:
      Increasing the firing rate of a lithotriptor can dramatically reduce the negative
      pressure component of the SWs, while the positive pressure remains virtually
      unaffected. Cavitation increases as the firing rate is increased but as the
      bubbles collapse, they break into numerous microbubbles that, because of their
      very small size, do not pose a barrier to the leading positive pressure of the
      next SW. These findings begin to explain why stone breakage in SWL becomes less
      efficient as the firing rate is increased.

PMID- 18710451
TI  - Lower urinary tract phenotype of experimental autoimmune cystitis in mouse: a
      potential animal model for interstitial cystitis.
AB  - OBJECTIVE: To examine bladder function in a newly developed experimental
      autoimmune cystitis (EAC) model in female SWXJ strain mice, as a potential animal
      model for interstitial cystitis (IC). MATERIALS AND METHODS: In all, 20 SWXJ
      female mice were divided into two groups: an EAC group immunized with mouse
      bladder homogenate in complete Freund's adjuvant (CFA) and a control group
      immunized with CFA alone. At 4 months after injection, the bladder function of
      some mice (six) was studied with 24-h micturition habits using metabolic cages
      and conscious cystometrography (CMG). The bladder and lung were harvested for
      histological examination and to assess interferon-gamma (IFN-gamma) mRNA
      expression. RESULTS: Histology examination showed obviously thickened lamina
      propria, infiltration of lymphocytes, giant cells, and increased mast cells in
      the detrusor muscle of the EAC mice. The lungs of EAC mice showed normal
      histology. The IFN-gamma mRNA expression increased significantly in the bladder,
      but not in the lung of the EAC mice. The 24-h micturition habits measurements
      showed increased frequency of urination in the EAC mice compared with the
      controls. Similarly, CMG showed decreased intercontraction intervals and voided
      volumes per micturition in the EAC mice compared with the controls. However,
      there were no significant differences in peak voiding pressure or total voiding
      volume between the EAC and control mice. CONCLUSIONS: Our murine EAC model has
      comparable functional and histological alterations to those seen in human IC, and
      may provide a useful model for the study of the pathogenesis and treatment of IC.

PMID- 18710452
TI  - Should molecular technology replace urine cytology?

PMID- 18710453
TI  - Ureteric stents compromise stone clearance after shockwave lithotripsy for
      ureteric stones: results of a matched-pair analysis.
AB  - OBJECTIVE: To identify the effect of the presence of a ureteric stent on the
      outcome of extracorporeal shockwave lithotripsy (ESWL), by comparing patients
      with ureteric stones with matched-pair analysis. PATIENTS AND METHODS: Patients
      undergoing ESWL with the Sonolith Vision lithotripter (Technomed Medical Systems,
      Vaulx-en-Velin, France) were identified from our prospectively maintained
      database. Only adult patients with a solitary, radio-opaque, previously untreated
      ureteric stone were considered for further analysis. A follow-up of >or=3 months
      with a plain abdominal film was used to identify residual fragments. Patients
      were exactly matched for gender, side, location in the ureter and size (in two
      dimensions, within +/-2 mm). If both diameters could not be matched exactly, the
      size was extended to +/-1 mm and then to +/-2 mm of both diameters. An effort was
      finally made to match patients by age. The treatment outcome in terms of stone
      free rates was assessed and compared using McNemar's test. RESULTS: In all, 45
      patients with a ureteric stent in place during ESWL were identified. The only
      patient who could not be adequately matched was a 40-year-old man with an 8 x 3
      mm stone in the upper ureter. The best/closest match for age was selected. Most
      stones were in the upper ureter (77%); the mean stone size was 8.5 and 8.6 mm,
      respectively, with no statistical differences between the groups for age and size
      of stones (P = 0.41 and 0.86, Student's t-test). In 12 pairs, only patients with
      no stent were stone-free, compared to two pairs where the patient with a stent
      was stone-free. Using McNemar's test, the odds ratio was 6.0 (95% confidence
      interval 1.3-55.2) and the difference between the groups was statistically
      significant (P = 0.016). CONCLUSION: These results show that the presence of a
      stent is associated with a worse outcome after ESWL for ureteric stones. Ureteric
      stents should still be used in cases of obstruction, when there is a risk of
      sepsis, and in patients with intolerable pain or deteriorating renal function.
      However, their use in patients offered ESWL for ureteric stones should be
      considered with caution.

PMID- 18710454
TI  - The continent, catheterizable abdominal conduit in adult urological practice.
AB  - OBJECTIVE: To report a large, single-centre experience with a continent,
      catheterizable abdominal conduit in adult patients. PATIENTS AND METHODS: We
      retrospectively reviewed the case notes of all 65 patients who had surgery to
      create a continent catheterizable conduit based on the Mitrofanoff principle.
      Operations were carried out over a 13-year period. Data on surgical procedure,
      complications and final outcome were collected and analysed. RESULTS: The mean
      age of the patients was 38.4 years and mean follow-up interval was 75.2 months.
      Patients with neuropathic lower urinary tracts accounted for the largest single
      indication for reconstruction (36 patients). The appendix was the conduit of
      choice and was available and suitable for use in 37 patients. There were 57
      patients who continued to use their native bladder or had undergone an
      augmentation or substitution cystoplasty; 24.5% of these 57 individuals had also
      undergone closure of the bladder neck or urethra. There were postoperative
      complications requiring laparotomy in five (8%) patients. In all, 30 patients
      (46%) had catheterization problems, but most of these were easy to treat. Five
      patients (8%) had an incontinent conduit which was a more difficult problem to
      deal with. Two patients have died of unrelated cause and five patients have been
      converted to an ileal conduit. In all, 58 patients (92%) now have a Mitrofanoff
      conduit, of which 97% are catheterizable and 95% are continent. CONCLUSIONS:
      Continent urinary diversion, based on the Mitrofanoff principle, has similar
      outcomes in adult urological practice to those described in published paediatric
      case series. There is good evidence to suggest that Mitrofanoff conduits are
      durable. However, patients should be aware of complications and the need for long
      term follow-up.

PMID- 18710455
TI  - Auricular acupuncture: a novel treatment for vasomotor symptoms associated with
      luteinizing-hormone releasing hormone agonist treatment for prostate cancer.
AB  - OBJECTIVES: To evaluate the role of auricular acupuncture (AA) in men receiving
      luteinizing-hormone releasing hormone (LHRH) analogues for carcinoma of the
      prostate, as vasomotor symptoms can affect the quality of life in such men, and
      similar symptoms in postmenopausal women have been successfully treated with AA.
      PATIENTS AND METHODS: In all, 60 consecutive patients with prostate cancer and on
      LHRH agonist treatment (median age 74 years, range 58-83) consented to weekly AA
      for 10 weeks. The validated 'Measure Yourself Concerns and Well-Being'
      questionnaire (a six-point scale to assess symptom severity) was used to assess
      concerns and well-being before and after treatment. RESULTS: All men completed
      the treatment with no adverse events recorded, apart from transient exacerbation
      of symptoms in two men; 95% of patients reported a decrease in the severity of
      symptoms, from a mean 5.0 to 2.1 (Student's t-test, P < 0.01). CONCLUSIONS: The
      symptomatic improvement was at levels comparable with that from pharmacotherapy,
      and cost analysis showed AA to be a viable alternative. Larger randomized studies
      are needed to fully evaluate AA against more conventional treatments, and these
      are planned.

PMID- 18710456
TI  - Prostate-specific antigen testing and prostate biopsy: are self-reported lower
      urinary tract symptoms and health-related quality of life associated with the
      decision to undergo these investigations?
AB  - OBJECTIVE: To investigate whether men's self-reported health-related quality of
      life and lower urinary tract symptoms (LUTS) are associated with acceptance of
      prostate-specific antigen (PSA) testing and subsequent prostate biopsy. PATIENTS
      AND METHODS: In a prospective questionnaire study of men aged 50-69 years, nested
      within the primary-care-based Prostate testing for cancer and Treatment study in
      nine UK areas, the Hospital Anxiety and Depression Scale (HADS), 12-item Short
      Form Health Survey (SF-12) and a self-reported LUTS measure (ICSmaleSF) were
      completed immediately before having a PSA test or prostate biopsy, or after not
      responding to an invitation for a PSA test or refusing a biopsy. Analyses
      compared 348 men accepting or 232 not responding to invitations for PSA testing
      and 318 accepting or 48 refusing a prostate biopsy. RESULTS: Men accepting or not
      responding to the invitation for a PSA test had similar HADS, SF-12 and LUTS
      scores. Men accepting a biopsy had similar HADS and SF-12 scores to those
      refusing biopsy, but significantly more LUTS (P < 0.01 for hesitancy, reduced
      stream, intermittency, incomplete emptying, frequency during the day).
      CONCLUSION: Depressed or anxious mood, comorbidity and LUTS were not associated
      with the decision to respond to invitations for a PSA test. Men agreeing to a
      biopsy were more likely to have LUTS than those refusing, suggesting that men
      believe that LUTS are a symptom of prostate cancer. Men needing a prostate biopsy
      require more information about LUTS so that they can make informed choices about
      testing for prostate cancer.

PMID- 18710457
TI  - The accuracy of transrectal ultrasonography supplemented with computer-aided
      ultrasonography for detecting small prostate cancers.
AB  - OBJECTIVE: To determine the extent to which computer-aided ultrasonography of the
      prostate (HistoScanning, Advanced Medical Diagnostics, Waterloo, Belgium) can
      identify tumour foci that correspond to a volume of >or=0.50 mL. PATIENTS AND
      METHODS: Between September 2004 and February 2006, 29 men were HistoScanned
      before scheduled radical prostatectomy. The three-dimensional raw (grey-scaled)
      data required for HistoScanning analysis were acquired by transrectal
      ultrasonography, and analysed using organ-specific tissue-characterization
      algorithms which form the core of the HistoScanning technology. The HistoScanning
      analysis results were compared with the histology of the whole-mounted prostate,
      step-sectioned sagittally at 5-mm intervals, and each slide analysed by 5 x 5 mm
      grid analysis. RESULTS: Of 29 patients, 13 had histology unknown to those
      evaluating the HistoScanning data. With 0.50 mL as the lower threshold for
      delineating and visualizing cancer volume, HistoScanning correctly predicted the
      presence of all 12 lesions that were subsequently confirmed to occupy >or=0.50
      mL. In addition three lesions were predicted as being present and of >or=0.50 mL.
      These three lesions were subsequently confirmed to be present but were <or=0.50
      mL on histopathological review. Thus, using the clinically accepted volume
      threshold of 0.50 mL, the sensitivity, specificity, positive and negative
      predictive value of HistoScanning were 12/12, 13/16 (82%), 12/15 (80%) and 12/12,
      respectively, for the cancer foci analysed. CONCLUSIONS: In this preliminary
      study, HistoScanning accurately detected cancer foci of >or=0.50 mL; these
      encouraging results will need to be verified in a larger group of patients.

PMID- 18710458
TI  - Pathological tumour diameter predicts risk of conventional subtype in small renal
      cortical tumours.
AB  - OBJECTIVE: To examine whether pathological tumour diameter assists in predicting
      conventional vs other histological subtypes in renal cortical tumours (RCTs) of
      <or=4 cm diameter. PATIENTS AND METHODS: In all, 393 patients from Columbia
      University's Comprehensive Urologic Oncology Database who underwent radical or
      partial nephrectomy between 1988 and 2005 and had RCTs of <or=4 cm were analysed.
      Logistic regression analysis using tumour diameter as a continuous variable was
      used to determine whether size predicted histological subtype. Odds ratios (ORs)
      were calculated to estimate the likelihood of having conventional histology based
      on diameter. RESULTS: The median patient age at surgery was 64.3 years and median
      tumour diameter was 3 cm, In all, 256 (65.1%) of the RCTs were conventional
      subtype and 137 (34.9%) were nonconventional. Logistic regression analysis showed
      that for every 1 cm increase in diameter up to 4 cm, the RCT was 1.27 times more
      likely to be conventional (P = 0.020). The ORs showed that a 4-cm RCT was 2.06
      times more likely to be conventional than tumours of 0.6-1.5 cm. CONCLUSION:
      There was a positive association between RCT diameter and the risk of having
      conventional renal cell carcinoma (RCC). Given that RCC histological subtype is a
      prognostic indicator for outcome, these findings may be applied in the selection
      of treatment options. Further studies investigating tumour size and other
      variables predictive of tumour histology will help clinicians better predict the
      RCC subtype.

PMID- 18710459
TI  - Catheter-less robotic radical prostatectomy using a custom-made synchronous
      anastomotic splint and vesical urinary diversion device: report of the initial
      series and perioperative outcomes.
AB  - OBJECTIVE: To study the feasibility of avoiding a urethral catheter after robotic
      radical prostatectomy by using suprapubic diversion with a urethral splint, as
      urethral catheterization is often a source of major discomfort and pain to the
      patient, and can cause more concern to the patient than the procedure; we present
      the outcomes of a pilot study. PATIENTS AND METHODS: This pilot study involved 30
      patients; in group 1 (the study group of 10 patients) we used a custom-made
      suprapubic catheter which provided a small anastomotic splint, multiple holes for
      drainage and the ability to retract the splint to give a voiding trial before
      removing the drainage device. Group 2 was a control group of 20 patients who had
      standard urethral catheterization with an 18 F Silastic Foley catheter.
      Demographic, intraoperative and outcome data were measured and analysed. Urethral
      symptoms were recorded using a specially developed questionnaire. RESULTS: The
      two groups were comparable in terms of age, serum prostate specific antigen
      level, body mass index, Gleason scores, tumour stage, operative duration, amount
      of bleeding, console times, anastomotic leakage and postoperative retention
      rates. The study group had significantly less penile shaft or tip pain and
      discomfort during walking or sleeping. No patient in either group had haematuria
      or clot retention requiring irrigation. CONCLUSION: Urethral catheter-less
      robotic radical prostatectomy is feasible. The advantages are decreased penile
      shaft and tip pain, and decreased patient discomfort and an earlier return of
      continence.

PMID- 18710460
TI  - Molecular mechanisms underlying group A streptococcal pathogenesis.
AB  - Group A Streptococcus (GAS) is a versatile human pathogen causing diseases
      ranging from uncomplicated mucosal infections to life-threatening invasive
      disease. The development of human-relevant animal models of GAS infection and
      introduction of new technologies have markedly accelerated the pace of
      discoveries related to GAS host-pathogen interactions. For example, recently
      investigators have identified pili on the GAS cell surface and learned that they
      are key components for adherence to eukaryotic cell surfaces. Similarly, the
      recent development of a transgenic mouse expressing human plasminogen has
      resulted in new understanding of the molecular processes contributing to invasive
      infection. Improved understanding of the molecular mechanisms underlying the
      pathogenesis of GAS pharyngeal, invasive and other infections holds the promise
      of assisting with the development of novel preventive or therapeutic agents for
      this prevalent human pathogen.

PMID- 18710461
TI  - Long-term plasma levels of leptin and adiponectin in Rett syndrome.
AB  - OBJECTIVE: Rett syndrome is a progressive neurological disorder affecting almost
      exclusively females after age 6 months and characterised by acquired
      microcephaly, psychomotor retardation, growth failure, purposeless hand
      movements, autistic-like behaviour and wide-based and stiff legged gait. Leptin
      and adiponectin, peptides secreted by adipose tissue, are involved in the
      regulation of body weight and energy expenditure. DESIGN AND PATIENTS: We
      investigated in patients with Rett syndrome the variations of plasma leptin and
      adiponectin and their relation over a 2-year period. Sixteen female patients,
      mean age at the basal time 9.4 +/- 4.3 years, with classical Rett syndrome were
      enrolled. Controls were 16 healthy female subjects, mean age at the basal time
      9.9 +/- 3.4 years. MEASUREMENTS: Blood samples were withdrawn in the morning at
      the baseline, 12 months after and 24 months after; plasma leptin and adiponectin
      concentrations were detected by ELISA. RESULTS: In patients, leptin
      concentrations significantly increased, while adiponectin concentrations
      significantly decreased. Both leptin and adiponectin values were significantly
      higher than those found in controls at each time. Leptin significantly correlated
      with adiponectin in patients, while there was not a significant correlation in
      controls. CONCLUSION: Since all patients were not obese, we might hypothesize
      that in Rett syndrome leptin and adiponectin might participate to clinical
      manifestations other than weight balance.

PMID- 18710462
TI  - Ghrelin concentrations in Prader-Willi syndrome (PWS) infants and children:
      changes during development.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is associated with failure to thrive in
      infancy and progressive hyperphagia and obesity in childhood. This progressive
      weight gain is associated with hyperghrelinaemia and increased insulin
      sensitivity. The role of ghrelin excess in the pathogenesis of obesity is
      unclear. OBJECTIVE: To determine if high ghrelin levels precede the onset of
      obesity in young PWS children. DESIGN AND METHODS: A cross-sectional study of 33
      infants with PWS and 28 healthy control subjects (C). Fasting ghrelin and other
      satiety hormones were measured. RESULTS: Median total serum ghrelin in young
      children with PWS trended higher, but did not differ significantly from those in
      C of similar age, weight-for-age z-score and sex. However, there was more
      variability in ghrelin concentrations of young PWS. Eleven of 33 PWS subjects had
      ghrelin levels greater than the 95th percentile for ghrelin values in the C
      subjects (> 2871 pg/ml). Six of the PWS subjects with high ghrelin levels had
      weight-for-age z-scores < 0. Ghrelin concentrations in PWS and C infants exceeded
      those in older children. In youngsters with PWS, leptin was higher, suggesting a
      relative excess of fat to lean body mass and plasma adiponectin was increased.
      CONCLUSIONS: Young infants with PWS who have not yet developed hyperphagia or
      obesity have median fasting ghrelin levels similar to controls. However, a subset
      (33%) of young PWS is hyperghrelinaemic; approximately one-half of those with
      hyperghrelinaemia have BMI z-score < 0. The age-related decline in ghrelin is
      blunted in PWS.

PMID- 18710463
TI  - Use of the Leksell gamma knife in the treatment of prolactinoma patients.
AB  - OBJECTIVE: Pharmacological treatment with dopaminergic agonists (DA) is the
      treatment of choice for prolactinomas. Surgical and radiation treatment is also
      indicated in certain situations. We describe our 12-year experience in treating
      prolactinomas with the Leksell gamma knife (LGK). DESIGN: We followed 35
      prolactinoma patients (25.7% microprolactinomas, 74.3% macroprolactinomas)
      treated with LGK irradiation. The mean follow-up period was 75.5 months. Prior to
      LGK irradiation, patients were treated with DA and 10 of them (28.6%) underwent
      neurosurgery. Indications for LGK irradiation were: DA intolerance (31.4%), DA
      resistance (45.7%) and efforts to reduce the DA dose or shorten the period of
      administration (22.9%). Pituitary function was monitored regularly at 6-month
      intervals. The central radiation dose range was 40-80 Gy (median 70 Gy), and the
      minimal peripheral dose was 20-49 Gy (median 34 Gy). RESULTS: Normoprolactinaemia
      was achieved in 37.1% of the patients who discontinued DA and in 42.9% of
      patients who continued DA treatment after LGK irradiation. The median time to
      prolactin normalization after discontinuation of DA was 96 months. No relapse was
      seen in any patient. After LGK irradiation, the prolactinoma stopped growing or
      decreased in size in all but one patient (97.1%). CONCLUSION: LGK treatment
      resulted in normoprolactinaemia in 80.0% of the patients, all of whom had failed
      pharmacological treatment due to DA resistance or intolerance. After achieving
      normoprolactinaemia, no relapse of hyperprolactinaemia was observed in any
      patient. The size of the adenoma decreased even in those patients in whom it was
      not changed by previous DA treatment.

PMID- 18710464
TI  - Effects of genetic variation in the aldosterone synthase (CYP11B2) gene on enzyme
      function.
AB  - OBJECTIVE: Evidence suggests that high levels of aldosterone lead to hypertension
      and increased risk of cardiovascular disease. Around 15% of patients with
      essential hypertension have a raised aldosterone to renin ratio (ARR) suggesting
      that aldosterone production is inappropriately high in relation to its principal
      agonist angiotensin II. This may be due to increased activity of aldosterone
      synthase caused by genetic variation in the CYP11B2 gene. We screened the coding
      region of human CYP11B2 for genetic variants and tested their effects on function
      in vitro. PROTOCOL: Normotensive subjects (n = 69) were screened for sequence
      variants in the coding region of CYP11B2 by single-stranded conformation
      polymorphism (SSCP) analysis and sequencing. The effects of nonsynonymous
      variants on enzyme activity were assessed in JEG-3 cells transiently transfected
      with wild-type or variant expression plasmids. The conversion of the substrate 11
      deoxycorticosterone (DOC) to corticosterone (B) and aldosterone was measured.
      RESULTS: Twenty variants were detected in CYP11B2 and eight analysed functionally
      (Arg87Gly, Asn281Thr, Gly288Ser, Lys296Asn, Asp335Asn, Gln404Arg, Ala414Pro and
      His439Tyr). Corticosterone synthesis was unaltered and aldosterone synthesis
      reduced in variant Arg87Gly; Asn281Thr increased corticosterone and decreased
      aldosterone production; Gly288Ser increased corticosterone production and
      abolished aldosterone production; Lys296Asn reduced both corticosterone and
      aldosterone production; Asp335Asn increased corticosterone synthesis but did not
      affect aldosterone production. Variants Gln404Arg, Ala414Pro and His439Tyr showed
      increases in both corticosterone and aldosterone synthesis compared to the wild
      type. CONCLUSION: The study confirms the genetic variability of the CYP11B2 gene
      and provides us with additional valuable structure-function information.

PMID- 18710466
TI  - Diagnostic value of salivary cortisol in Cushing's syndrome (CS).
AB  - OBJECTIVE: The diagnosis of Cushing's syndrome (CS) remains a challenge in
      clinical endocrinology. The aim of this study was to determine the
      reproducibility and diagnostic value of late-night salivary cortisol (SAF(23))
      for CS and its utility along the follow-up of treated patients. In addition,
      using the same radioimmunoassay reactives, the cut-off values for saliva and
      serum cortisol, assessed synchronically after the overnight 1 mg dexamethasone
      suppression test (DST), were defined. DESIGN: Twenty-one patients with confirmed
      CS and 121 volunteers were studied. All the subjects collected 24-h urine for
      cortisol (UFC). On the same day whole saliva was obtained from the subjects at 23
      h for SAF(23). The intraclass coefficient of correlation (ICC) of SAF(23) was
      estimated in 47 subjects (21 CS and 26 C). At 8 h, after DST, simultaneous saliva
      and serum samples for cortisol (SAF(dex) and F(dex), respectively) were obtained
      in 51 subjects (17 CS and 34 C). After specific therapy, 18 patients with CS were
      followed with SAF(23) measurements. SAF and F were expressed as nM. RESULTS: The
      intraclass coefficient of correlation of SAF(23) was 0.89 in CS and 0.83 in C.
      SAF(23) > 3.8 nM showed a sensitivity and specificity of 100% and 97.5%,
      respectively, for diagnosing CS. SAF(23) correlated positively with UFC (r =
      0.685; P = 0.0001). After DST, SAF(dex) significantly correlated with F(dex) (r =
      0.61, P < 0.0001). A cut-off value of SAF(dex) > 2.0 nM and F(dex) > 50.0 nM
      detected CS with 100% sensitivity and specificity. After successful surgical
      therapy, 13 patients with CS had SAF(23) levels < 3.8 nM (1.4 +/- 0.8 nM).
      CONCLUSIONS: SAF(23) and SAF(dex) seem to be good screening tools based on their
      noninvasive nature, remarkable reproducibility and diagnostic performances.

PMID- 18710465
TI  - Characterization of the anaemia associated with Graves' disease.
AB  - BACKGROUND: Graves' disease (GD) is associated with hyperthyroidism.
      Thyrotoxicosis adversely affects multiple organ systems including haematopoiesis.
      Anaemia occurring specifically in GD has not been systematically studied
      previously. OBJECTIVE: To define the prevalence and characteristics of the
      anaemia associated with GD. DESIGN: Eighty-seven newly diagnosed patients with GD
      were recruited. Haematological indices, thyroid function and inflammatory
      parameters were examined at presentation and following successful treatment of
      hyperthyroidism. SETTING: Tertiary care academic referral centre. RESULTS: Thirty
      three per cent of subjects presented with anaemia. The prevalence of anaemia not
      attributable to other causes (GD anaemia) was 22%. GD anaemia affected 41.6%
      (10/24) of men compared to 17.5% of women (11/63). Mean erythropoietin (EPO)
      levels (15.5 +/- 5.3 mIU/ml) were within normal reference limits but
      significantly higher (P = 0.004) than those of the non-anaemic controls. Hgb
      correlated inversely with EPO (P = 0.05) and CRP (P = 0.04) levels, a
      relationship that persisted after multivariate adjustment for TT3 or TT4. With
      antithyroid therapy for 16 +/- 6.3 weeks, Hgb levels normalized in 8 out of 9
      subjects with GD anaemia (10.7 +/- 0.8 to 13.5 +/- 1.3 g/dl, P = 0.0001). After
      normalization of Hgb, mean MCV and TIBC were significantly increased, and median
      ferritin and mean EPO were significantly decreased. CONCLUSIONS: GD anaemia is
      common, resembles the anaemia of chronic disease, and is associated with markers
      of inflammation. It corrects promptly with return to the euthyroid state
      following treatment.

PMID- 18710467
TI  - The tryptophan 620 allele of the lymphoid tyrosine phosphatase (PTPN22) gene
      predisposes to autoimmune Addison's disease.
AB  - OBJECTIVE: Previous studies of the association between autoimmune Addison's
      disease (AAD) and a nonsynonymous single nucleotide polymorphism (SNP) in the
      PTPN22 gene (C1858T, pR620W; SNP ID no. rs2476601) have shown conflicting
      results. We aimed to examine this association using additional cohorts of AAD
      subjects from the UK and Poland. DESIGN: DNA samples were obtained from UK and
      Polish AAD subjects (n = 251 and 87, respectively) and ethnically matched healthy
      controls (n = 429 and 236, respectively). Genotyping for the C1858T PTPN22 marker
      was performed by polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP) assay. Meta-analysis of the results, together with those
      from three other populations, was performed using RevMan v5.0 software. RESULTS:
      In 251 UK AAD subjects the frequency of the PTPN22 1858T allele was 12.2%
      compared to 7.8% in healthy UK controls; P = 0.008. Similarly, in 87 Polish AAD
      subjects the PTPN22 1858T allele was found in 19.5% of alleles compared to 11.7%
      in healthy Polish subjects; P = 0.010. A meta-analysis, combining these result
      with published data for three other populations, involving 797 AAD subjects and
      2032 controls in total, showed that the 1858T allele was associated with AAD
      susceptibility with a pooled odds ratio (OR) of 1.44 [95% confidence interval
      (CI) 1.21-1.72; P = 5.6 x 10(-5)], under a fixed-effects model. CONCLUSION: This
      study confirms the association between the PTPN22 1858T allele and AAD in an
      expanded UK cohort and in the previously unstudied Polish population. This meta
      analysis allows for the first time a reliable estimate of the strength of effect
      of this autoimmune disease susceptibility allele across different European
      Caucasian populations.

PMID- 18710468
TI  - Assessment of p27 (cyclin-dependent kinase inhibitor 1B) and aryl hydrocarbon
      receptor-interacting protein (AIP) genes in multiple endocrine neoplasia (MEN1)
      syndrome patients without any detectable MEN1 gene mutations.
AB  - OBJECTIVE: Germline mutations in the MEN1 gene predispose to the multiple
      endocrine neoplasia (MEN1) syndrome; however, approximately 10-20% of patients
      with MEN1 do not have a detectable MEN1 mutation. A rat strain with multiple
      endocrine tumours, a phenotypic overlap of both MEN1 and MEN2, has been reported
      to have a homozygous germline p27 (CDKN1B) mutation. Recently, two MEN1 mutation
      negative MEN1 syndrome patients have been identified to harbour a germline CDKN1B
      mutation. The recently identified gene AIP can also cause familial isolated
      pituitary adenoma, but no other specific tumour is associated with this syndrome.
      The objective of this study was to evaluate the possible contribution of CDKN1B
      and AIP germline mutations in a cohort of MEN1 mutation-negative MEN1 syndrome
      patients. PATIENTS: Eighteen sporadic and three familial cases of MEN1 mutation
      negative MEN1 syndrome were studied (18 pituitary adenomas, 12
      hyperparathyroidism, 10 neuroendocrine tumours including 2 ACTH-secreting lesions
      and one adrenal nodular hyperplasia). Clinical data and genomic DNA were analysed
      for mutations in the CDKN1B and AIP genes. RESULTS: There were no mutations in
      the coding region or exon/intron junction of the CDKN1B and AIP genes in any
      patient. Although we have a limited number of patients in our cohort, our data is
      consistent with others in the literature suggesting that CDKN1B and AIP mutations
      are extremely rare in MEN1 syndrome. CONCLUSION: Our results suggest that
      mutations in the CDKN1B and AIP genes are relatively uncommon in MEN1 mutation
      negative MEN1 syndrome patients.

PMID- 18710469
TI  - Effects of rehabilitation treatment on thyroid function.
AB  - OBJECTIVE: The aim of the study was to evaluate the effects of an intensive
      rehabilitation programme on thyroid metabolism, the relationship between
      disability and thyroid hormone level, and the occurrence of nonthyroidal illness
      syndrome (NTIS) before and after rehabilitation. DESIGN, SUBJECTS AND
      MEASUREMENTS: This was a clinical prospective study. Orthopaedic surgery patients
      (n = 82) were classified into two groups: patients in whom early active
      mobilization and walking were possible (walking group, WG, n = 45), and patients
      in whom these were not recommended (nonwalking group, NWG, n = 37). Levels of
      free T3 (fT3), fT4, TSH and rT3 were measured before and after surgery, and then
      at 1, 3, 7, 14 and 30 days from the beginning of rehabilitation. Personal,
      nutritional and clinical data were acquired for all patients. The Barthel Index
      (BI) was used to assess disability before and after rehabilitation. RESULTS:
      Immediately after surgery, both groups of patients showed a significant decrease
      in mean fT3 concentrations and a significant increase in rT3; mean fT4 values
      decreased significantly only in NWG patients. Once rehabilitation had been
      completed, fT3 and rT3 levels returned to baseline values in WG patients. In NWG
      patients mean fT3 and fT4 levels continued to decrease significantly and rT3
      values remained significantly high until the end of rehabilitation. NTIS occurred
      in 38% of the NWG patients. No significant changes in TSH levels were observed in
      either group. Finally, we observed a direct correlation between fT3 levels and
      the BI in WG patients. CONCLUSIONS: Our data suggest that early patient
      mobilization and physical activity during an active and intensive rehabilitation
      programme induce recovery of thyroid function and avoid occurrence of NTIS.

PMID- 18710470
TI  - Prevalence and functional analysis of the S107P polymorphism (rs6647476) of the
      monocarboxylate transporter 8 (SLC16A2) gene in the male population of north-west
      Spain (Galicia).
AB  - OBJECTIVE: Mutations in SLC16A2, the gene encoding the thyroid hormone (TH)
      specific transporter monocarboxylate transporter 8 (MCT8), result in a thyroid
      phenotype and severe mental retardation caused by neuronal TH deficiency. These
      mutational effects raise the question of whether polymorphic variation in SLC16A2
      may also be associated with differences in serum levels of TH and/or TSH. DESIGN:
      This is the first major study of the frequency of the SLC16A2 rs6647476 single
      nucleotide polymorphism (SNP) (amino acid change Ser107Pro). We also studied the
      relationships of SLC16A2 genetic variants with serum levels of TSH, T4 and T3,
      with their mRNA expression and with expression of the TH-responsive genes ZAKI-4
      and BTEB in white blood cells. Experiments in cultured fibroblasts were carried
      out to ascertain the dynamics of the T3 response. METHODS: A total of 276 men
      were studied. Genotyping of the S107P SNP was carried out using polymerase chain
      reaction restriction fragment length polymorphism (PCR-RFLP); serum hormone
      levels were determined by chemiluminescence; expression of mRNA was quantified by
      real-time PCR. RESULTS: The SLC16A2 S107P SNP was found in 36% of Galician males.
      With the present sample size we did not find any association of this polymorphism
      with variability in serum levels of TSH, free T4 (fT4) or fT3, or with basal
      expression of mRNA for SLC16A2 or the two TH-responsive genes ZAKI-4 and BTEB,
      either in white blood cells or in cultured human fibroblasts from either Ser107
      or Pro107 genotypes under T3 stimulation. CONCLUSIONS: The S107P change in MCT8
      is frequent in the male population in Galicia. In the population studied in this
      report an association with a thyroid phenotype was not demonstrated, even though
      the S107P SNP causes an important amino acid change.

PMID- 18710471
TI  - Expression of iodine metabolism genes in human thyroid tissues: evidence for age
      and BRAFV600E mutation dependency.
AB  - CONTEXT: Children present a higher susceptibility to developing thyroid cancer
      after radioiodine exposure and also a higher frequency of functional metastases
      than adults. OBJECTIVE: To assess the mRNA expression of the sodium/iodide
      (Na(+)/I(-)) symporter (NIS), the Pendred syndrome gene (PDS), thyroperoxidase
      (TPO), thyroglobulin (Tg) and TSH receptor (TSH-R) in normal thyroid tissues
      (NTTs) and papillary thyroid carcinomas (PTCs) among different age groups.
      METHODS: Analysis included 59 samples: 21 NTTs and 38 PTCs, of which 21 were the
      classic type (CPTC) and 17 the follicular variant (FVPTC). Patients were divided
      into three age groups: I (n = 16) 5-21 years, II (n = 13) 22-59 years, and III (n
      = 10) 60-91 years. The relative mRNA expression of the five target genes was
      determinate by quantitative reverse transcription polymerase chain reaction (QRT
      PCR). RESULTS: Expression of all genes was significantly higher in NTTs than in
      PTCs, and it was not age dependent in the NTT group. Among PTCs, the mean
      expression of PDS, TPO and TSH-R was significantly lower in group II than in
      group I. PDS, TPO and Tg expression was significantly lower in classic PTCs than
      in FVPTCs. The difference was related to a higher frequency of the BRAF(V600E)
      mutation in the former group. CONCLUSIONS: The finding of higher PDS, TPO and TSH
      R mRNA expression in paediatric vs. adult primary tumour tissues supports the
      hypothesis that this might contribute to the increased functional activity of
      metastases in the paediatric group. The finding that mRNA expression of the
      target genes in NTT was not age dependent does not provide an explanation for the
      higher susceptibility in the paediatric group.

PMID- 18710473
TI  - Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese
      women.
AB  - OBJECTIVE: Lipocalin family proteins, including adipocyte fatty acid-binding
      protein (A-FABP), lipocalin-2 and retinol-binding protein 4 (RBP4), have recently
      been identified as novel adipokines associated with obesity, type 2 diabetes and
      the metabolic syndrome. We have evaluated the effect of exercise training on
      lipocalin family proteins and inflammatory markers. STUDY SUBJECTS: Thirty obese
      Korean women and 15 age-matched nonobese control subjects were studied. DESIGN:
      Concentrations of the lipocalin family proteins were compared between obese and
      nonobese women and were evaluated before and 3 months after an exercise programme
      consisting of aerobic exercise (45 min/session, 300 kcal/day) and muscle strength
      training (20 min/session, 100 kcal/day) five times a week. RESULTS: Obese women
      exhibited higher A-FABP levels compared to nonobese women (21.4 +/- 6.4 microg/l
      vs. 13.6 +/- 4.4 microg/l, P < 0.001). However, neither lipocalin-2 nor RBP4
      levels were significantly different between the two groups, although the
      difference in lipocalin-2 was marginally significant (P = 0.054). Circulating A
      FABP levels were significantly associated with body mass index (BMI), waist
      circumference, triglyceride, alanine aminotransferase (ALT), lipocalin-2 and high
      sensitivity C-reactive protein (hsCRP) levels. After 3 months of the exercise
      training programme, serum A-FABP levels decreased significantly from 21.4 +/- 6.4
      microg/l to 19.3 +/- 6.8 microg/l (P = 0.038), along with a reduction in weight,
      BMI, waist circumference, fasting glucose and total cholesterol levels. There was
      no significant change in the lipocalin-2 and RBP4 levels, although IL-6 levels
      increased after the exercise programme. CONCLUSION: Exercise training with weight
      loss induced a significant reduction in circulating A-FABP levels in obese Korean
      women.

PMID- 18710472
TI  - Resistin gene variation is associated with systemic inflammation but not plasma
      adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic
      Caucasians.
AB  - OBJECTIVE: Resistin causes insulin resistance and diabetes in mice whereas in
      humans it is linked to inflammation and atherosclerosis. Few human genetic
      studies of resistin in inflammation and atherosclerosis have been performed. We
      hypothesized that the -420C>G putative gain-of-function resistin variant would be
      associated with inflammatory markers and atherosclerosis but not with metabolic
      syndrome or adipokines in humans. DESIGN AND METHODS: We examined the association
      of three resistin polymorphisms, -852A>G, -420C>G and +157C>T, and related
      haplotypes with plasma resistin, cytokines, C-reactive protein (CRP), adipokines,
      plasma lipoproteins, metabolic syndrome and coronary artery calcification (CAC)
      in nondiabetic Caucasians (n = 851). RESULTS: Resistin levels were higher, dose
      dependently, with the -420G allele (CC 5.9 +/- 2.7 ng/ml, GC 6.5 +/- 4.0 ng/ml
      and GG 7.2 +/- 4.8 ng/ml, trend P = 0.04) after age and gender adjustment [fold
      higher for GC + GG vs. CC; 1.07 (1.00-1.15), P < 0.05)]. The -852A>G single
      nucleotide polymorphism (SNP) was associated with higher soluble tumour necrosis
      factor-receptor 2 (sol-TNFR2) levels in fully adjusted models [1.06 (95% CI 1.01
      1.11), P = 0.01)]. The estimated resistin haplotype (GGT) was associated with sol
      TNFR2 (P = 0.04) and the AGT haplotype was related to CRP (P = 0.04) in the fully
      adjusted models. Resistin SNPs and haplotypes were not associated with body mass
      index (BMI), fasting glucose, insulin resistance, metabolic syndrome, adipokines
      or CAC scores. CONCLUSIONS: Despite modest associations with plasma resistin and
      inflammatory biomarkers, resistin 5' variants were not associated with metabolic
      parameters or coronary calcification. This suggests that resistin is an
      inflammatory cytokine in humans but has little influence on adiposity, metabolic
      syndrome or atherosclerosis.

PMID- 18710474
TI  - Sexual dimorphism of high molecular weight adiponectin in cord blood.

PMID- 18710475
TI  - Altered protease signalling in the gut: a novel pathophysiological factor in
      irritable bowel syndrome.

PMID- 18710476
TI  - The role of the endocannabinoid system in the pathophysiology and treatment of
      irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a spectrum of disorders characterized by
      abdominal discomfort and pain, associated with altered bowel habits. Though gut
      motility, secretion and sensation may be altered in patients with IBS, the
      pathophysiology of this condition remains to be fully understood. The
      endocannabinoid system is involved in the regulation of numerous gastrointestinal
      functions including motility, sensation and secretion under both physiological
      and pathophysiological conditions. Activation of cannabinoid (CB)(1) and CB(2)
      receptors under various circumstances reduces motility, limits secretion and
      decreases hypersensitivity in the gut. Drugs that alter the levels of
      endocannabinoids in the gut also reduce motility and attenuate inflammation. In
      this review, we discuss the role of the endocannabinoid system in
      gastrointestinal physiology. We go on to consider the involvement of the
      endocannabinoid system in the context of symptoms associated with IBS and a
      possible role of this system in the pathophysiology and treatment of IBS.

PMID- 18710477
TI  - Temporal epidemiology of microfilaraemia among migrant workers entering Kuwait.
AB  - BACKGROUND: There is paucity of published data on the microfilarial infection
      among migrants from endemic countries entering Kuwait. The primary objectives of
      this study were to use routine health surveillance data to i) to estimate the
      prevalence of microfilarial infection in migrant workers to Kuwait and ii) to
      determine the occurrence of any time trends in the proportions of microfilaria
      positives among these workers over the recent past. METHODS: Monthly aggregates
      of microfilaria thick slide test results obtained from routine health
      examinations of migrant workers conducted at the Ports and Border Health Division
      of Ministry of Health, Kuwait between January 1, 1992 and December 31, 2006, were
      available for trend analysis of these time series data. RESULTS: During the study
      period, the prevalence (per 100,000) of microfilaraemia positive migrant workers
      was 48 (1169/2449360). A third-order polynomial regression model of monthly
      proportions of microfilaraemic workers revealed a significant initial increase
      (beta(1) = 2.976 (+/- 0.157); P < 0.001), followed by a significant declining
      trend (beta(2) = -0.0358 (+/- 0.002); P < 0.001) and a slight but significant
      upward trend (beta(3) = 0.0001 (+/- < 0.001); P < 0.001) towards the end of study
      period. CONCLUSION: This study showed a recent steady but apparently asymptotic
      decline in the prevalence of microfilarial infection in migrant workers from
      filarial endemic countries to Kuwait.This may reflect either changes in the socio
      economic backgrounds of recent migrants or the effects of recently initiated mass
      drug administration programs carried out in the endemic countries of origin.

PMID- 18710478
TI  - MarkerSet: a marker selection tool based on markers location and informativity in
      experimental designs.
AB  - BACKGROUND: The recent sequencing of full genomes has led to the availability of
      many SNP markers which are very useful for the mapping of complex traits. In
      livestock production, there are still no commercial arrays and many studies use
      home-made sets of SNPs. Thus, the current methodologies for SNP genotyping are
      still expensive and it is a crucial step to select the SNPs to use. Indeed, the
      main factors affecting the power of the linkage analyses are the density of the
      genetic map and the heterozygosity of markers in tested animal parents. FINDINGS:
      This is why we have developed a PERL program selecting a defined number of
      markers based on their locations on the genome and their informativity in
      specific experimental designs. As an option, different experimental designs can
      be combined in order to select the best possible common marker set. The program
      has been tested using different conditions of marker informativity and density
      with both real and simulated datasets. The results show the efficiency of our
      program to select the most informative markers even if there is a wide range of
      informativity for whole genome scan mapping analyses. In case of combination of
      different experimental crosses, the multidesign mode can optimize the SNP markers
      selection. CONCLUSION: Written in PERL, it assures a maximum portability to other
      operating systems (OS) and the source code availability for user modifications.
      Except for the simulation mode which could be time consuming, MarkerSet can
      compute results in a very short time.

PMID- 18710479
TI  - Multiplex preamplification of specific cDNA targets prior to gene expression
      analysis by TaqMan Arrays.
AB  - BACKGROUND: An accurate gene expression quantification using TaqMan Arrays (TA)
      could be limited by the low RNA quantity obtained from some clinical samples. The
      novel cDNA preamplification system, the TaqMan PreAmp Master Mix kit (TPAMMK),
      enables a multiplex preamplification of cDNA targets and therefore, could provide
      a sufficient amount of specific amplicons for their posterior analysis on TA.
      FINDINGS: A multiplex preamplification of 47 genes was performed in 22 samples
      prior to their analysis by TA, and relative gene expression levels of non
      preamplified (NPA) and preamplified (PA) samples were compared. Overall, the mean
      cycle threshold (CT) decrement in the PA genes was 3.85 (ranging from 2.07 to
      5.01). A high correlation (r) between the gene expression measurements of NPA and
      PA samples was found (mean r = 0.970, ranging from 0.937 to 0.994; p < 0.001 in
      all selected cases). High correlation coefficients between NPA and PA samples
      were also obtained in the analysis of genes from degraded RNA samples and/or low
      abundance expressed genes. CONCLUSION: We demonstrate that cDNA preamplification
      using the TPAMMK before TA analysis is a reliable approach to simultaneously
      measure gene expression of multiple targets in a single sample. Moreover, this
      procedure was validated in genes from degraded RNA samples and low abundance
      expressed genes. This combined methodology could have wide applications in
      clinical research, where scarce amounts of degraded RNA are usually obtained and
      several genes need to be quantified in each sample.

PMID- 18710480
TI  - Contemporary evidence: baseline data from the D2B Alliance.
AB  - BACKGROUND: Less than half of U.S. hospitals meet guidelines for prompt treatment
      of ST-segment elevation myocardial infarction (STEMI). The Door-to-Balloon (D2B)
      Alliance is a collaborative effort of more than 900 hospitals committed to
      implementing a set of evidence-based strategies for reducing D2B time. This study
      presents data on (1) the prevalence of evidence-based strategies in U.S.
      hospitals that participated in the D2B Alliance and (2) identifies key hospital
      characteristics associated with their use. METHODS: We conducted a cross
      sectional study of U.S. hospitals that joined the D2B Alliance through a Web
      based survey about their current practices for patients with STEMI who received
      primary percutaneous coronary intervention (PCI). We used multivariate logistic
      regression to identify hospital characteristics associated with use of each
      strategy. RESULTS: Of the 915 U.S. hospitals enrolled in the D2B Alliance as of
      June 2007, 797 (87%) completed the survey. Only 30.4% of responding hospitals
      reported employing at least 4 of the 5 key strategies (emergency medicine
      activates catheterization laboratory, single-call activation, expectation that
      catheterization team is available in the laboratory within 20-30 minutes after
      page, prompt data feedback on D2B times, use of pre-hospital electrocardiograms
      to activate the laboratory while the patient is en route to the hospital); 9.3%
      employed none of the strategies. There was no clear pattern of correlation
      between hospital characteristics and reported strategies. CONCLUSION: As of 2007,
      many hospitals had implemented few of the key strategies to reduce D2B time,
      suggesting substantial opportunity to improve care for patients with STEMI.

PMID- 18710481
TI  - An audit of Colposcopy referrals from a GU/STD clinic.
AB  - BACKGROUND: Cervical cancer is increasing at 1.5% per year in Ireland with 50%
      mortality giving 2.2% of all cancer deaths. In the Mid-West region a pilot
      screening programme has begun to screen all women 25-60 years. 66% of
      Genitourinary/Sexually transmitted disease (GU/STD) clinics' abnormal smears are
      <25 years. Requests to abandon "opportunistic" screening prompted this GU/STD
      clinic audit. METHODS: 221(8.4%) patients referred to colposcopy over 4 years
      were audited. Retrospective analysis was carried out on GU/STD clinic files,
      hospital files and computer records for biopsy reports. Ethical approval was
      prospectively granted. RESULTS: 2637 smears were carried out from November 1999 -
      September 2003.221 patients referred to colposcopy were audited.1%, 3%, 5% had
      severe, moderate and, mild dyskaryosis, respectively, on cervical screening while
      0.8%, 1.2%, 1.5% had CIN3, CIN2, CIN1 abnormalities, respectively, on biopsy with
      3.5% having no abnormality (Cervical Intraepithelial Neoplasia = CIN).53%
      referred to colposcopy were <25 years. CONCLUSION: 2% had high grade lesions. 37%
      of high grade lesions are <25 years.Of the high grade lesions 13% had Chlamydia
      trachomatis (27% of CIN3) and 44% had HPV despite Relative Risks (RR) being 0.75
      and 1.09 respectively. Older women had higher grade changes. No statistical
      difference was found for progression, regression and persistence in those over
      and under 25.

PMID- 18710482
TI  - Common dietary flavonoids inhibit the growth of the intraerythrocytic malaria
      parasite.
AB  - BACKGROUND: Flavonoids are abundant plant phenolic compounds. More than 6000 have
      been identified to date, and some have been shown to possess antiparasitic
      activity. Here we investigate the effects of a range of common dietary flavonoids
      on the growth of two strains of the human malaria parasite Plasmodium falciparum.
      FINDINGS: A chloroquine-sensitive (3D7) and a chloroquine-resistant (7G8) strain
      of P. falciparum were tested for in vitro susceptibility to a range of individual
      dietary flavonoids and flavonoid combinations. Parasite susceptibility was
      measured in 96-well plates over 96 h using a previously described
      [3H]hypoxanthine incorporation assay. Of the eleven flavonoids tested, eight
      showed antiplasmodial activity against the 3D7 strain (with IC50 values between
      11 and 66 muM), and all showed activity against the 7G8 strain (with IC50 values
      between 12 and 76 muM). The most active compound against both strains was
      luteolin, with IC50 values of 11 +/- 1 muM and 12 +/- 1 muM for 3D7 and 7G8,
      respectively. Luteolin was found to prevent the progression of parasite growth
      beyond the young trophozoite stage, and did not affect parasite susceptibility to
      the antimalarial drugs chloroquine or artemisinin. Combining low concentrations
      of flavonoids was found to produce an apparent additive antiplasmodial effect.
      CONCLUSION: Certain common dietary flavonoids inhibit the intraerythrocytic
      growth of the 3D7 and 7G8 strains of P. falciparum. Flavonoid combinations
      warrant further investigation as antiplasmodial agents.

PMID- 18710483
TI  - PhosCalc: a tool for evaluating the sites of peptide phosphorylation from mass
      spectrometer data.
AB  - BACKGROUND: We have created a software implementation of a published and verified
      method for assigning probabilities to potential phosphorylation sites on peptides
      using mass spectrometric data. Our tool, named PhosCalc, determines the number of
      possible phosphorylation sites and calculates the theoretical masses for the b
      and y fragment ions of a user-provided peptide sequence. A corresponding user
      provided mass spectrum is examined to determine which putative b and y ions have
      support in the spectrum and a probability score is calculated for each
      combination of phosphorylation sites. FINDINGS: We test the implementation using
      spectra of phosphopeptides from bovine beta-casein and we compare the results
      from the implementation to those from manually curated and verified
      phosphopeptides from our own experiments. We find that the PhosCalc scores are
      capable of helping a user to identify phosphorylated sites and can remove a
      bottleneck in high throughput proteomics analyses. CONCLUSION: PhosCalc is
      available as a web-based interface for examining up to 100 peptides and as a
      downloadable tool for examining larger numbers of peptides. PhosCalc can be used
      to speed up identification of phosphorylation sites and can be easily integrated
      into data handling pipelines making it a very useful tool for those involved in
      phosphoproteomic research.

PMID- 18710484
TI  - Analysis of gene expression patterns by microarray hybridization in blood
      mononuclear cells of SLA-DRB1 defined Canadian Yorkshire pigs.
AB  - BACKGROUND: The Swine Leukocyte Antigen (SLA) system encodes molecules for self
      nonself discrimination and is associated with immune responses and disease
      resistance. Three lines of pigs defined by their SLA-DRB1 alleles were developed
      at the University of Guelph for xenotransplantation and immune response studies.
      The aim of this project was to explore the potential association between defined
      SLA-DRB1 alleles and gene transcriptional patterns of other immune-related genes
      in blood mononuclear cells. FINDINGS: Three SLA-DRB1 alleles were characterized
      using a RT-PCR-based sequencing method. The loci represented included a new
      allele, DRB1*04ns01. Next, microarray heterologous (bovine-porcine) hybridization
      together with qPCR were used to explore differential gene expression between SLA
      DRB1-defined groups. Microarray analysis showed significant (p < 0.01)
      differential expression for 5 genes, mostly related to inflammation. Genes varied
      according to the comparison analyzed. Further testing with qPCR revealed the same
      trend of differential expression for 4 of the genes, although statistical
      significance was reached for only one. CONCLUSION: A new SLA-DRB1 allele was
      characterized. A potential association was found between SLA-DRB1 alleles and
      inflammation-related genes. However, the influence of other genes cannot be ruled
      out. These preliminary findings agree with other studies linking MHC haplotypes
      and inflammation processes, including autoimmune disease. The study provides an
      initial view of the biological interactions between the SLA complex and other
      immune-related genes. Future studies will focus on characterization of SLA
      haplotypes associated with these particular alleles and the dynamics of the
      immune response to antigenic challenges.

PMID- 18710485
TI  - A sequencing strategy for identifying variation throughout the prion gene of BSE
      affected cattle.
AB  - BACKGROUND: Classical and atypical bovine spongiform encephalopathies (BSEs) are
      cattle prion diseases. Distinct bovine prion gene (PRNP) alleles have been
      associated with classical and atypical BSE susceptibility. However, the full
      extent of PRNP allele association with BSE susceptibility is not known. A
      systematic sequence-based genotyping method that detects variation throughout
      PRNP would be useful for: 1) detecting rare PRNP alleles that may be present in
      BSE-affected animals and 2) testing PRNP alleles for an association with either
      classical or atypical BSE susceptibility. FINDINGS: We improved a Sanger-based
      sequencing strategy for detecting bovine PRNP variation through all exons,
      introns, and part of the promoter (25.2 kb). Our current method can detect 389
      known and other potentially unknown PRNP polymorphisms that may be present in BSE
      affected cattle. We determined PRNP genotypes for the first U.S. BSE case and her
      sire. Previously unknown PRNP polymorphisms were not detected in either animal
      and all PRNP genotypes support the sire-daughter relationship. CONCLUSION: The
      methodologies described here characterize variation throughout PRNP.
      Consequently, rare PRNP alleles that may be present in BSE-affected cattle can be
      detected.

PMID- 18710486
TI  - Genome-wide screens for effective siRNAs through assessing the size of siRNA
      effects.
AB  - BACKGROUND: RNA interference (RNAi) has been seen as a revolution in functional
      genomics and system biology. Genome-wide RNAi research relies on the development
      of RNAi high-throughput screening (HTS) assays. One of the most fundamental
      challenges in RNAi HTS is to glean biological significance from mounds of data,
      which relies on the development of effective analytic methods for selecting
      effective small interfering RNAs (siRNAs). FINDINGS: Based on a recently proposed
      parameter, strictly standardized mean difference (SSMD), I propose an analytic
      method for genome-wide screens of effective siRNAs through assessing and testing
      the size of siRNA effects. Central to this method is the capability of SSMD in
      quantifying siRNA effects. This method has relied on normal approximation, which
      works only in the primary screens but not in the confirmatory screens. In this
      paper, I explore the non-central t-distribution property of SSMD estimates and
      use this property to extend the SSMD-based method so that it works effectively in
      either primary or confirmatory screens as well as in any HTS screens with or
      without replicates. The SSMD-based method maintains a balanced control of false
      positives and false negatives. CONCLUSION: The central interest in genome-wide
      RNAi research is the selection of effective siRNAs which relies on the
      development of analytic methods to measure the size of siRNA effects. The new
      analytic method for hit selection provided in this paper offers a good analytic
      tool for selecting effective siRNAs, better than current analytic methods, and
      thus may have broad utility in genome-wide RNAi research.

PMID- 18710487
TI  - Chocolate bar as an incentive did not increase response rate among
      physiotherapists: a randomised controlled trial.
AB  - BACKGROUND: The aim of this study was to assess the effect of a small incentive,
      a bar of dark chocolate, on response rate in a study of physiotherapy performance
      in patients with knee osteoarthritis. FINDINGS: Norwegian physiotherapists from
      private practice were randomised in blocks to an intervention group (n = 1027)
      receiving a bar of dark chocolate together with a data-collection form, and a
      control group (n = 1027) that received the data-collection form only. The
      physiotherapists were asked to prospectively complete the data-collection form by
      reporting treatments provided to one patient with knee osteoarthritis through 12
      treatment sessions. The outcome measure was response rate of completed forms.Out
      of the 510 physiotherapists that responded, 280 had completed the data-collection
      form by the end of the study period. There was no difference between the
      chocolate and no-chocolate group in response rate of those who sent in completed
      forms. In the chocolate group, 142 (13.8%) returned completed forms compared to
      138 (13.4%) in the control group, ARR = 0.4 (95% CI: -3.44 to 2.6). CONCLUSION: A
      bar of dark chocolate did not increase response rate in a prospective study of
      physiotherapy performance. Stronger incentives than chocolate seem to be
      necessary to increase the response rate among professionals who are asked to
      report about their practice. TRIAL REGISTRATION: Current Controlled Trials
      register: ISRCTN02397855.

PMID- 18710488
TI  - The inverse starving test is not a suitable provocation test for Gilbert's
      syndrome.
AB  - INTRODUCTION: The aim of this study was to evaluate a simple diagnostic test for
      Gilbert's syndrome (GS), which avoids hospitalization and exposure to toxic test
      substrates. GS is the most frequent cause of isolated unconjugated
      hyperbilirubinemia. The nicotinic acid test and the starving test are established
      approaches to diagnose GS. However, these tests cause considerable side effects
      or require hospital admission. In single GS patients, we observed rapid serum
      bilirubin normalization after a standard European lunch (the "inverse starving
      test"). FINDINGS: At two consecutive days, 18 profoundly characterized GS
      patients (7 females, 11 males, median age 34.5 years, range 21-58 years) were
      investigated with the nicotinic acid test and the inverse starving test.
      Unconjugated serum bilirubin (UCB) levels were measured before and hourly up to
      four hours after lunch (median 645 kcal), and after the ingestion of 170
      milligrams nicotinic acid, respectively. Patients who consulted their physicians
      with jaundice were significantly more likely to undergo invasive diagnostic
      procedures than patients with an incidental finding of elevated UCB, despite UCB
      levels were indifferent in both groups. Two hours after nicotinic acid ingestion,
      relative UCB exceeded 1.7 fold the fasting levels (median, range 0.9-2.4 fold,
      sensitivity 83%). In the inverse starving test, UCB remained almost unchanged
      three hours after lunch (median 1.0; range: 0.8-1.2 fold). Molecular analysis
      established the genotype of the TATAA box of the UGT1A1 gene; all patients
      carried an UGT1A1 promotor polymorphism. CONCLUSION: The inverse starving test is
      not an appropriate provocation test for patients with suspected GS. The 100%
      prevalence of the UGT1A1 polymorphism in our cohort underlines that the diagnosis
      of GS may be substantiated with this simple molecular test in patients with an
      uncertain diagnosis of GS.

PMID- 18710489
TI  - Evidence for bacteriophage T7 tail extension during DNA injection.
AB  - BACKGROUND: Electron micrographs of bacteriophage T7 reveal a tail shorter than
      needed to reach host cytoplasm during infection-initiating injection of a T7 DNA
      molecule through the tail and cell envelope. However, recent data indicate that
      internal T7 proteins are injected before the DNA molecule is injected. Thus,
      bacteriophage/host adsorption potentially causes internal proteins to become
      external and lengthen the tail for DNA injection. But, the proposed adsorption
      induced tail lengthening has never been visualized. FINDINGS: In the present
      study, electron microscopy of particles in T7 lysates reveals a needle-like
      capsid extension that attaches partially emptied bacteriophage T7 capsids to non
      capsid vesicles and sometimes enters an attached vesicle. This extension is 40-55
      nm long, 1.7-2.4x longer than the T7 tail and likely to be the proposed
      lengthened tail. The extension is 8-11 nm in diameter, thinner than most of the
      tail, with an axial hole 3-4 nm in diameter. Though the bound vesicles are not
      identified by microscopy, these vesicles resemble the major vesicles in T7
      lysates, found to be E. coli outer membrane vesicles by non-denaturing agarose
      gel electrophoresis, followed by mass spectrometry. CONCLUSION: The observed
      lengthened tail is long enough to reach host cytoplasm during DNA injection. Its
      channel is wide enough to be a conduit for DNA injection and narrow enough to
      clamp DNA during a previously observed stalling/re-starting of injection.
      However, its outer diameter is too large to explain formation by passing of an
      intact assembly through any known capsid hole unless the hole is widened.

PMID- 18710490
TI  - Health-related quality of life in a trial of acupuncture, sham acupuncture and
      conventional treatment for chronic sinusitis.
AB  - BACKGROUND: Acupuncture is commonly used to treat chronic sinusitis, though there
      is little documentation on the effect. This study presents the health-related
      quality of life (HRQoL) outcomes in a trial comparing traditional Chinese
      acupuncture, sham acupuncture, and conventional treatment for chronic sinusitis.
      FINDINGS: In a three-armed single blind randomized controlled study, we recruited
      65 patients with symptoms of sinusitis >3 months and signs of sinusitis on
      computed tomography (CT). Patients were randomized to one of three study arms:
      (1) 2-4 weeks of medication with antibiotics, corticosteroids, 0.9% sodium
      chloride solution, and local decongestants (n = 21), (2) ten treatments with
      traditional Chinese acupuncture (n = 25), or (3) ten treatments with minimal
      acupuncture at non-acupoints (n = 19). Change in HRQoL was assessed over 12 weeks
      using the Chronic Sinusitis Survey (CSS) and Short form 36 (SF-36)
      questionnaires.In the study, we found only a non-significant difference on the
      CSS symptom scale between conventional medical therapy and traditional Chinese
      acupuncture. On the SF-36 scale role-physical the change was larger in the
      conventional group than in the sham group (p = 0.02), and on the mental health
      scale the change in the conventional therapy arm was larger than in the
      traditional Chinese acupuncture group (p = 0.03). There was no difference in
      effect on HRQoL on any scale between the sham and traditional Chinese acupuncture
      groups. CONCLUSION: There was no clear evidence of the superiority of one
      treatment over another on short-term HRQoL outcomes, although there was a
      statistically non-significant advantage of conventional therapy in a few
      dimensions.

PMID- 18710491
TI  - Amyloid-beta peptide degradation in cell cultures by mycoplasma contaminants.
AB  - BACKGROUND: Cell cultures have become an indispensable tool in Alzheimer's
      disease research for studying amyloid-beta (Abeta) metabolism. It is estimated
      that up to 35% of cell cultures in current use are infected with various
      mycoplasma species. In contrast with common bacterial and fungal infections,
      contaminations of cell cultures with mycoplasmas represent a challenging issue in
      terms of detectability and prevention. Mycoplasmas are the smallest and simplest
      self-replicating bacteria and the consequences of an infection for the host cells
      are variable, ranging from no apparent effect to induction of apoptosis.
      FINDINGS: Here we present evidence that mycoplasmas from a cell culture
      contamination are able to efficiently and rapidly degrade extracellular Abeta. As
      a result, we observed no accumulation of Abeta in the conditioned medium of
      mycoplasma-positive cells stably transfected with the amyloid-beta precursor
      protein (APP). Importantly, eradication of the mycoplasma contaminant -
      identified as M. hyorhinis - by treatments with a quinolone-based antibiotic,
      restored extracellular Abeta accumulation in the APP-transfected cells.
      CONCLUSION: These data show that mycoplasmas degrade Abeta and thus may represent
      a significant source of variability when comparing extracellular Abeta levels in
      different cell lines. On the basis of these results, we recommend assessment of
      mycoplasma contaminations prior to extracellular Abeta level measurements in
      cultured cells.

PMID- 18710492
TI  - Reduction of the pulse duration of the ultrafast laser pulses of the Two-Photon
      Laser Scanning Microscopy (2PLSM).
AB  - BACKGROUND: We provide an update of our two-photon laser scanning microscope by
      compressing or reducing the broadening of the pulse width of ultrafast laser
      pulses for dispersion precompensation, to enable the pulses to penetrate deeply
      inside the sample. FINDINGS: The broadening comes as the pulses pass through the
      optical elements. We enhanced and modified the quality and the sharpness of
      images by enhancing the resolution using special polarizer namely Glan Laser
      polarizer GL10. This polarizer consists of two prisms separated by air space.
      This air separation between the two prisms uses to delay the red wavelength when
      the light leaves the first prism to the air then to second prism. We note a
      considerable enhancing with using the GL polarizer, and we can see the details of
      the leaf structure in early stages when we trying to get focus through z-stacks
      of images in comparison to exactly the same measurements without using GL
      polarizer. Hence, with this modification we able to reduce the time of exposure
      the sample to the laser radiation thereby we will reduce the probability of
      photobleaching and phototoxicity. When the pulse width reduced, the average power
      of the laser pulses maintained at a constant level. Significant enhancement is
      found between the two kinds of images of the Two-Photon Excitation Fluorescence
      (TPEF). CONCLUSION: In summary reduction the laser pulse width allowed to collect
      more diffraction orders which will used to form the images. The more diffraction
      orders the higher resolution images.

PMID- 18710493
TI  - Statistical analysis of post mortem DNA damage-derived miscoding lesions in
      Neandertal mitochondrial DNA.
AB  - BACKGROUND: We have analysed the distribution of post mortem DNA damage derived
      miscoding lesions from the datasets of seven published Neandertal specimens that
      have extensive cloned sequence coverage over the mitochondrial DNA (mtDNA)
      hypervariable region 1 (HVS1). The analysis was restricted to C-->T and G-->A
      miscoding lesions (the predominant manifestation of post mortem damage) that are
      seen at a frequency of more than one clone among sequences from a single PCR, but
      do not represent the true endogenous sequence. FINDINGS: The data indicates an
      extreme bias towards C-->T over G-->A miscoding lesions (observed ratio of 67:2
      compared to an expected ratio of 7:2), implying that the mtDNA Light strand
      molecule suffers proportionally more damage-derived miscoding lesions than the
      Heavy strand. CONCLUSION: The clustering of Cs in the Light strand as opposed to
      the singleton pattern of Cs in the Heavy strand could explain the observed bias,
      a phenomenon that could be further tested with non-PCR based approaches. The
      characterization of the HVS1 hotspots will be of use to future Neandertal mtDNA
      studies, with specific regards to assessing the authenticity of new positions
      previously unknown to be polymorphic.

PMID- 18710494
TI  - Sub-parts per billion detection of trace volatile chemicals in human breath using
      selected ion flow tube mass spectrometry.
AB  - BACKGROUND: Selected ion flow tube mass spectrometry (SIFT-MS) allows the real
      time quantification of trace gases in air. Due to its tolerance of high humidity
      levels the technique is particularly suited to the chemical analysis of breath.
      The detection limit of SIFT-MS has previously reported to be approximately 5 - 10
      PPBV which is insufficient for the measurement of some low abundance constituents
      of breath. Recent developments in the design of SIFT-MS instruments have
      increased the ion precursor count rates. It is, however, unclear as to how these
      advances will affect instrument sensitivity for breath analysis. FINDINGS:
      Standard gases were prepared by adding known quantities of compounds present at
      zero or very low levels in breath (xylene and toluene) to either humidified
      bottled air or actual human breath. These were then analysed by SIFT-MS to
      calculate the limits of detection for each compound under conditions which mimic
      a single breath exhalation. For xylene and toluene the limits of detection was
      approximately 0.5 PPBV per 10 seconds of analysis time. Results gained using this
      level of sensitivity suggested the presence of low levels of the compounds indole
      and methylindole in human alveolar and static oral air, although further studies
      are necessary to confirm these findings. CONCLUSION: Recent advances in SIFT-MS
      have increased the techniques sensitivity for breath analysis into the sub PPBV
      range enabling the real time quantification of low level trace gases in human
      breath.

PMID- 18710495
TI  - Biologically active fibroblast growth factor 1 tagged with various epitopes.
AB  - BACKGROUND: Fibroblast growth factor (FGF) family members are involved in the
      regulation of a variety of biological phenomena. Because most of their activity
      is exerted via a signaling complex composed of FGF, heparin/heparan sulfate and
      FGF receptor tyrosine kinase, it is important to study the dynamic behavior of
      all the molecules in the complex without disturbing their interaction or
      activity. FINDINGS: We used E. coli to express biologically active human FGF1
      tagged at its C-terminus with myc-(His)6, V5-(His)6 or 3xFLAG-(His)6. We found
      that the tagged FGF1s had affinities for heparin that were similar to that of the
      native form. The tagged FGF1s also exhibited mitogenic activity similar to that
      of the native form. Apparently, the tags do not interfere with the formation of
      the three-member complex involving FGF1, FGF receptor and heparan
      sulfate/heparin. CONCLUSION: Tagged FGF1s should be useful for investigating the
      dynamic behavior of FGF1 in the context of its three-member signaling complex and
      other molecular complexes.

PMID- 18710496
TI  - Stress regulated members of the plant organic cation transporter family are
      localized to the vacuolar membrane.
AB  - BACKGROUND: In Arabidopsis six genes group into the gene family of the organic
      cation transporters (OCTs). In animals the members of the OCT-family are mostly
      characterized as polyspecific transporters involved in the homeostasis of
      solutes, the transport of monoamine neurotransmitters and the transport of
      choline and carnitine. In plants little is known about function, localisation and
      regulation of this gene family. Only one protein has been characterized as a
      carnitine transporter at the plasma membrane so far. FINDINGS: We localized the
      five uncharacterized members of the Arabidopsis OCT family, designated OCT2-OCT6,
      via GFP fusions and protoplast transformation to the tonoplast. Expression
      analysis with RNA Gel Blots showed a distinct, organ-specific expression pattern
      of the individual genes. With reporter gene fusion of four members we analyzed
      the tissue specific distribution of OCT2, 3, 4, and 6. In experiments with salt,
      drought and cold stress, we could show that AtOCT4, 5 and 6 are up-regulated
      during drought stress, AtOCT3 and 5 during cold stress and AtOCT 5 and 6 during
      salt stress treatments. CONCLUSION: Localisation of the proteins at the tonoplast
      and regulation of the gene expression under stress conditions suggests a specific
      role for the transporters in plant adaptation to environmental stress.

PMID- 18710497
TI  - Progress in the PRIDE technique for rapidly comparing protein three-dimensional
      structures.
AB  - BACKGROUND: Accurate and fast tools for comparing protein three-dimensional
      structures are necessary to scan and analyze large data sets. FINDINGS: The
      method described here is not only very fast but it is also reasonable precise, as
      it is shown by using the CATH database as a test set. Its rapidity depends on the
      fact that the protein structure is represented by vectors that monitors the
      distribution of the inter-residue distances within the protein core and the
      structure of which is optimized with the Freedman-Diaconis rule. CONCLUSION: The
      similarity score is based on a chi2 test, the probability density function of
      which can be accurately estimated.

PMID- 18710498
TI  - Development and application of a microarray meter tool to optimize microarray
      experiments.
AB  - BACKGROUND: Successful microarray experimentation requires a complex interplay
      between the slide chemistry, the printing pins, the nucleic acid probes and
      targets, and the hybridization milieu. Optimization of these parameters and a
      careful evaluation of emerging slide chemistries are a prerequisite to any large
      scale array fabrication effort. We have developed a 'microarray meter' tool which
      assesses the inherent variations associated with microarray measurement prior to
      embarking on large scale projects. FINDINGS: The microarray meter consists of
      nucleic acid targets (reference and dynamic range control) and probe components.
      Different plate designs containing identical probe material were formulated to
      accommodate different robotic and pin designs. We examined the variability in
      probe quality and quantity (as judged by the amount of DNA printed and remaining
      post-hybridization) using three robots equipped with capillary printing pins.
      DISCUSSION: The generation of microarray data with minimal variation requires
      consistent quality control of the (DNA microarray) manufacturing and experimental
      processes. Spot reproducibility is a measure primarily of the variations
      associated with printing. The microarray meter assesses array quality by
      measuring the DNA content for every feature. It provides a post-hybridization
      analysis of array quality by scoring probe performance using three metrics, a) a
      measure of variability in the signal intensities, b) a measure of the signal
      dynamic range and c) a measure of variability of the spot morphologies.

PMID- 18710499
TI  - Hepatic steatosis in patients with HIV-Hepatitis C Virus coinfection: is it
      associated with antiretroviral therapy and more advanced hepatic fibrosis?
AB  - BACKGROUND AND AIMS: Patients with HIV and hepatitis C virus (HCV) coinfection
      are at increased risk of developing hepatic steatosis. The aims of this study
      were to assess the prevalence of steatosis in a cohort with HIV-HCV coinfection,
      and to determine an association, if any, between steatosis, antiretroviral
      therapy (ART), and advanced hepatic fibrosis. PATIENTS AND METHODS: HIV-HCV
      coinfected patients were retrospectively identified from the HIV clinic. ART was
      classified as none, nucleoside reverse transcriptase inhibitors (NRTIs) only,
      highly active antiretroviral therapy (HAART) only, and sequential therapy
      (initial NRTIs followed by HAART). Fibrosis stage and necroinflammation grade
      were assessed by the modified HAI (Ishak) scoring method. Steatosis was graded as
      0-3. RESULTS: Sixty patients were identified. The overall prevalence of hepatic
      steatosis was 58%. Those that received HAART only had a lower prevalence of
      steatosis (41%) compared to those on NRTIs only (70%) or sequential therapy
      (82%). Independent predictors of hepatic steatosis were absence of HAART only
      therapy, OR 2.9, p = 0.09, and presence of cirrhosis, OR 4.6, p = 0.044. Forty
      five percent of the patients had advanced fibrosis (fibrosis stage >/= 3). NI
      grade (OR 1.9, p = 0.030), and steatosis grade (OR 3.6, p = 0.045), were
      independent predictors of advanced fibrosis. CONCLUSION: Hepatic steatosis is
      associated with more advanced hepatic fibrosis in the HIV-HCV coinfected
      population. HAART only therapy (rather than NRTIs only or sequential therapy)
      appears to be associated with a lower prevalence of hepatic steatosis. This may
      be one of the mechanisms by which HAART could attenuate hepatic fibrosis in such
      a cohort.

PMID- 18710500
TI  - Selection of reference genes for qRT-PCR examination of wild populations of
      Atlantic cod Gadus morhua.
AB  - BACKGROUND: Extensive sequencing efforts have been taking place for the Atlantic
      cod (Gadus morhua) in recent years, the number of ESTs in the Genbank has reached
      more than 140.000. Despite its importance in North Atlantic fisheries and
      potential use in aquaculture, relatively few gene expression examination exists
      for this species, and systematic evaluations of reference gene stability in
      quantitative real-time RT-PCR (qRT-PCR) studies are lacking. RESULTS: The
      stability of 10 potential reference genes was examined in six tissues of Atlantic
      cod obtained from four populations, to determine the most suitable genes to be
      used in qRT-PCR analyses. Relative transcription levels of genes encoding beta
      actin (ACTB), elongation factor 1A (EF1A), actin-related protein-2 (ARP-2),
      glyceraldehyde-3P-dehydrogenase (GAPDH), ubiquitin (Ubi), acidic ribosomal
      protein (ARP), ribosomal protein S9 (S9), ribosomal protein L4 (RPL4), RPL22 and
      RPL37 were quantified in gills, brain, liver, head kidney, muscle and middle
      intestine in six juvenile fish from three wild populations and from farmed
      Atlantic cod. Reference gene stability was investigated using the geNorm and
      NormFinder tools. Based on calculations performed with the geNorm, which
      determines the most stable genes from a set of tested genes in a given cDNA
      sample, ARP, Ubi, S9 and RPL37 were among the most stable genes in all tissues.
      When the same calculations were done with NormFinder, the same genes plus RPL4
      and EF1A were ranked as the preferable genes. CONCLUSION: Overall, this work
      suggests that the Ubi and ARP can be useful as reference genes in qRT-PCR
      examination of gene expression studying wild populations of Atlantic cod.

PMID- 18710501
TI  - Radical prostatectomies in Austria, 1997-2004.
AB  - BACKGROUND: The introduction of PSA testing in Austria led to a steep increase of
      the incidence of prostate cancer. We want to present the course of the number of
      newly diagnosed cases of prostate cancer in Austria since 1997, and set these
      numbers in relation to the total of radical prostatectomies (with resection of
      lymph nodes) in the same time period. All numbers were retrieved from health
      statistics of Statistics Austria. The report period of cancer cases and of RPE
      comprises the years 1997-2004. All calculations were performed for totals as well
      as for 5-year age groups (40-89 years of age). FINDINGS: The number of prostate
      cancer cases rose from 1997 to 2004 by 35%, while the number of RPE rose by 94%
      in the same time period. The proportion of RPE in relation to new cases rose from
      41% in 1997 to 59% in 2004. CONCLUSION: A slight decrease of prostate cancer
      mortality can already be observed in Austria, but the question of over-treatment
      still awaits analysis.

PMID- 18710502
TI  - Fisher: a program for the detection of H/ACA snoRNAs using MFE secondary
      structure prediction and comparative genomics - assessment and update.
AB  - BACKGROUND: The H/ACA family of small nucleolar RNAs (snoRNAs) plays a central
      role in guiding the pseudouridylation of ribosomal RNA (rRNA). In an effort to
      systematically identify the complete set of rRNA-modifying H/ACA snoRNAs from the
      genome sequence of the budding yeast, Saccharomyces cerevisiae, we developed a
      program - Fisher - and previously presented several candidate snoRNAs based on
      our analysis 1. FINDINGS: In this report, we provide a brief update of this work,
      which was aborted after the publication of experimentally-identified snoRNAs 2
      identical to candidates we had identified bioinformatically using Fisher. Our
      motivation for revisiting this work is to report on the status of the candidate
      snoRNAs described in 1, and secondly, to report that a modified version of Fisher
      together with the available multiple yeast genome sequences was able to correctly
      identify several H/ACA snoRNAs for modification sites not identified by the
      snoGPS program 3. While we are no longer developing Fisher, we briefly consider
      the merits of the Fisher algorithm relative to snoGPS, which may be of use for
      workers considering pursuing a similar search strategy for the identification of
      small RNAs. The modified source code for Fisher is made available as
      supplementary material. CONCLUSION: Our results confirm the validity of using
      minimum free energy (MFE) secondary structure prediction to guide comparative
      genomic screening for RNA families with few sequence constraints.

PMID- 18710503
TI  - Educational inequalities in self-reported health in a general Iranian population.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between
      educational level and self-reported health in an Iranian population, in order to
      provide evidence on social inequalities in health from a country in which such
      data need to be collected. METHODS: This population-based study was carried out
      in Tehran, Iran. Individuals aged 15 years and over were interviewed. Self
      reported health was measured by asking each individual to respond to the
      question: "In general how would you describe your health at present?" We used
      years of formal education as a measure of socioeconomic status and categorized
      the answers in five levels. Logistic regression analysis was used to estimate
      odds ratios and 95% confidence intervals indicating the contribution of
      educational level to self-reported health, adjusting for age, gender, marital
      status, and chronic diseases. RESULTS: In all, 4163 individuals were interviewed.
      The mean age of the respondents was 35.1 years (SD = 16.0); 52% were female; the
      mean duration of formal education was 10.0 years (SD = 4.5); and 31% rated their
      health 'less than good'. Overall, women rated their health more poorly than men
      (P < 0.0001), and the findings showed that those with higher education rated
      their health significantly better than those with lower educational levels after
      adjusting for the age, gender, marital status and chronic diseases. The odds
      ratio for having 'less than good' self-rated health in those at the lowest
      educational level compared with those at the highest was 2.65 (95% CI = 1.88
      3.73). CONCLUSION: The findings indicated an inverse relationship between
      educational level and self-rated health, and that age, gender, and chronic
      conditions had independent effects on self-reported health status. The findings
      of this first study from Iran suggest that health inequalities in developing
      countries such as Iran need to be addressed and policies for tackling the problem
      should be considered. In this respect, less well-educated people and women should
      be seen as the first target populations. It seems that although expanding the
      educational system might help the state to provide people with more educational
      options, it is also necessary to ensure that equal opportunities and access to
      quality education are provided for those from lower socioeconomic backgrounds;
      otherwise the current situation might cost the government more in the long term
      because of poor health among disadvantaged groups.

PMID- 18710504
TI  - Prediction of protein secondary structures with a novel kernel density estimation
      based classifier.
AB  - BACKGROUND: Though prediction of protein secondary structures has been an active
      research issue in bioinformatics for quite a few years and many approaches have
      been proposed, a new challenge emerges as the sizes of contemporary protein
      structure databases continue to grow rapidly. The new challenge concerns how we
      can effectively exploit all the information implicitly deposited in the protein
      structure databases and deliver ever-improving prediction accuracy as the
      databases expand rapidly. FINDINGS: The new challenge is addressed in this
      article by proposing a predictor designed with a novel kernel density estimation
      algorithm. One main distinctive feature of the kernel density estimation based
      approach is that the average execution time taken by the training process is in
      the order of O(nlogn), where n is the number of instances in the training
      dataset. In the experiments reported in this article, the proposed predictor
      delivered an average Q3 (three-state prediction accuracy) score of 80.3% and an
      average SOV (segment overlap) score of 76.9% for a set of 27 benchmark protein
      chains extracted from the EVA server that are longer than 100 residues.
      CONCLUSION: The experimental results reported in this article reveal that we can
      continue to achieve higher prediction accuracy of protein secondary structures by
      effectively exploiting the structural information deposited in fast-growing
      protein structure databases. In this respect, the kernel density estimation based
      approach enjoys a distinctive advantage with its low time complexity for carrying
      out the training process.

PMID- 18710505
TI  - Hand-held internet tablets for school-based data collection.
AB  - BACKGROUND: In the last 20 years, researchers have been using computer self
      administered questionnaires to gather data on a wide range of adolescent health
      related behaviours. More recently, researchers collecting data in schools have
      started to use smaller hand-held computers for their ease of use and portability.
      The aim of this study is to describe a new technology with wi-fi enabled hand
      held internet tablets and to compare adolescent preferences of laptop computers
      or hand-held internet tablets in administering a youth health and well-being
      questionnaire in a school setting. METHODS: A total of 177 students took part in
      a pilot study of a national youth health and wellbeing survey. Students were
      randomly assigned to internet tablets or laptops at the start of the survey and
      were changed to the alternate mode of administration about half-way through the
      questionnaire. Students at the end of the questionnaire were asked which of the
      two modes of administration (1) they preferred, (2) was easier to use, (3) was
      more private and confidential, and (4) was easier to answer truthfully. RESULTS:
      Many students expressed no preference between laptop computers or internet
      tablets. However, among the students who expressed a preference between laptop
      computers or internet tablets, the majority of students found the internet
      tablets more private and confidential (p < 0.001) and easier to answer questions
      truthfully (p < 0.001) compared to laptop computers. CONCLUSION: This study
      demonstrates that using wi-fi enabled hand-held internet tablets is a feasible
      methodology for school-based surveys especially when asking about sensitive
      information.

PMID- 18710506
TI  - Different media and supplements modulate the clonogenic and expansion properties
      of rabbit bone marrow mesenchymal stem cells.
AB  - BACKGROUND: Rabbits provide an excellent model for many animal and human
      diseases, such as cardiovascular diseases, for the development of new vaccines in
      wound healing management and in the field of tissue engineering of tendon,
      cartilage, bone and skin.The study presented herein aims to investigate the
      biological properties of bone marrow rabbit MSCs cultured in different
      conditions, in order to provide a basis for their clinical applications in
      veterinary medicine. FINDINGS: MSCs were isolated from 5 New Zealand rabbits.
      Fold increase, CFU number, doubling time, differentiation ability and
      immunophenotype were analyzed.With the plating density of 10 cells/cm2 the fold
      increase was significantly lower with DMEM-20%FCS and MSCs growth was
      significantly higher with alphaMEM-hEGF. The highest clonogenic ability was found
      at 100 cell/cm2 with MSCBM and at 10 cell/cm2 with M199. Both at 10 and 100
      cells/cm2, in alphaMEM medium, the highest CFU increase was obtained by adding
      bFGF. Supplementing culture media with 10%FCS-10%HS determined a significant
      increase of CFU. CONCLUSION: Our data suggest that different progenitor cells
      with differential sensitivity to media, sera and growth factors exist and the
      choice of culture conditions has to be carefully considered for MSC management.

PMID- 18710507
TI  - A new approach to primer design for the control of PCR bias in methylation
      studies.
AB  - Primer design for PCR-based methylation analysis following bisulfite conversion
      of DNA is considerably more complex than primer design for regular PCR. The
      choice of the optimal primer set is critical to the performance and correct
      interpretation of the results. Most methodologies in methylation analysis utilize
      primers that theoretically amplify methylated and unmethylated templates at the
      same time. The proportional amplification of all templates is critical but
      difficult to achieve due to PCR bias favouring the amplification of the
      unmethylated template. The focus of this brief communication is to point out the
      important criteria needed for the successful choice of primers that will enable
      the control of PCR bias in bisulfite based methylation-screening protocols.

PMID- 18710508
TI  - Cigarette smoking and associated factors among in-school adolescents in Jamaica:
      comparison of the Global Youth Tobacco Surveys 2000 and 2006.
AB  - BACKGROUND: We conducted this study to estimate the correlates of current
      cigarette smoking among in-school adolescents in Jamaica 2006 and compare
      prevalence of smoking and associated factors between 2000 and 2006. RESULTS: In
      2006, 1854 participated of whom 49.5 were males and 50.5% females. 1752
      adolescents, 48.8% male and 51.2% females participated in the 2000 survey.
      Between 2000 and 2006, the prevalence of smoking among Jamaican school-going
      adolescents went up slightly from 15.2% to 16.7% but this was not statistically
      significant (p = 0.22). The perception that smoking is not harmful increased from
      10.9% to 15.9% while parental smoking decreased from 39.4% to 35.5%. There was a
      decrease in the rates of adolescents exposed to tobacco adverts on billboards (p
      value = 0.037) and in newspapers/magazine (p-value < 0.001). The percentage of
      adolescents who reported having an item with a tobacco brand logo on it increased
      from 13.9% to 16.4%. The perception that boys and girls who smoked had more
      friends increased between 2000 and 2006 (p-values = 0.016 and 0.004
      respectively). Current smoking was associated with male gender (OR = 1.55; 95% CI
      [1.09-2.19]), having smoking parents (OR = 1.75; 95% CI [1.23-2.50]), and smoking
      friends (OR = 14.94; 95% CI [8.61-25.92] for most or all friends smokers and OR =
      4.38; 95% CI [2.93-6.56] for some friends smokers)). CONCLUSION: Results from
      this study indicate smoking was positively associated with male gender, having
      smoking friends or parents. We observed a slightly non significant increase in
      the prevalence of smoking between 2000 and 2006 among adolescents in Jamaica.
      Although there was a decrease in the rates of adolescents exposed to
      advertisement, the percentage of those who had an item with a tobacco brand logo
      had increased. The possible impact of the Jamaica's ratification of the Framework
      Convention on Tobacco control remains to be observed.

PMID- 18710509
TI  - Whole genome amplification and its impact on CGH array profiles.
AB  - BACKGROUND: Some array comparative genomic hybridisation (array CGH) platforms
      require a minimum of micrograms of DNA for the generation of reliable and
      reproducible data. For studies where there are limited amounts of genetic
      material, whole genome amplification (WGA) is an attractive method for generating
      sufficient quantities of genomic material from miniscule amounts of starting
      material. A range of WGA methods are available and the multiple displacement
      amplification (MDA) approach has been shown to be highly accurate, although
      amplification bias has been reported. In the current study, WGA was used to
      amplify DNA extracted from whole blood. In total, six array CGH experiments were
      performed to investigate whether the use of whole genome amplified DNA (wgaDNA)
      produces reliable and reproducible results. Four experiments were conducted on
      amplified DNA compared to unamplified DNA and two experiments on unamplified DNA
      compared to unamplified DNA. FINDINGS: All the experiments involving wgaDNA
      resulted in a high proportion of losses and gains of genomic material.
      Previously, amplification bias has been overcome by using amplified DNA in both
      the test and reference DNA. Our data suggests that this approach may not be
      effective, as the gains and losses introduced by WGA appears to be random and are
      not reproducible between different experiments using the same DNA. CONCLUSION: In
      light of these findings, the use of both amplified test and reference DNA on CGH
      arrays may not provide an accurate representation of copy number variation in the
      DNA.

PMID- 18710510
TI  - Conservation of CD44 exon v3 functional elements in mammals.
AB  - BACKGROUND: The human CD44 gene contains 10 variable exons (v1 to v10) that can
      be alternatively spliced to generate hundreds of different CD44 protein isoforms.
      Human CD44 variable exon v3 inclusion in the final mRNA depends on a multisite
      bipartite splicing enhancer located within the exon itself, which we have
      recently described, and provides the protein domain responsible for growth factor
      binding to CD44. FINDINGS: We have analyzed the sequence of CD44v3 in 95
      mammalian species to report high conservation levels for both its splicing
      regulatory elements (the 3' splice site and the exonic splicing enhancer), and
      the functional glycosaminglycan binding site coded by v3. We also report the
      functional expression of CD44v3 isoforms in peripheral blood cells of different
      mammalian taxa with both consensus and variant v3 sequences. CONCLUSION: CD44v3
      mammalian sequences maintain all functional splicing regulatory elements as well
      as the GAG binding site with the same relative positions and sequence identity
      previously described during alternative splicing of human CD44. The sequence
      within the GAG attachment site, which in turn contains the Y motif of the exonic
      splicing enhancer, is more conserved relative to the rest of exon. Amplification
      of CD44v3 sequence from mammalian species but not from birds, fish or reptiles,
      may lead to classify CD44v3 as an exclusive mammalian gene trait.

PMID- 18710511
TI  - Primary antimicrobial resistance among Mycobacterium tuberculosis isolates from
      HIV seropositive and HIV seronegative patients in Dar es Salaam Tanzania.
AB  - BACKGROUND: The United Republic of Tanzania is one of the 22 high M. tuberculosis
      burden countries. Data collected between 2002 and 2007 indicate that the global
      prevalence of drug-resistant M. tuberculosis including MDR vary greatly. The
      varied drug-resistance patterns make continuous surveillance of drug resistance
      an essential component of tuberculosis control program. FINDINGS: M. tuberculosis
      isolates were obtained from consenting adult tuberculosis patients involved in a
      placebo-controlled study to evaluate the efficacy of multivitamin supplements on
      response to anti-Tb treatment in Dar es Salaam, Tanzania. Antimicrobial
      susceptibility testing was done on four antimicrobial agents namely streptomycin,
      isoniazid, ethambutol and rifampicin. HIV testing and CD4+ T lymphocytes
      enumeration were also done. A total of 280 M. tuberculosis isolates from 191
      (68%) males and 89 (32%) female patients with no previous history of anti
      tuberculosis treatment exceeding 4 weeks in the previous 12 months were tested.
      Among these, 133 (47%) patients were HIV seropositive. Fourteen (5.0%) isolates
      were resistant to any of the anti-tuberculosis drugs. The prevalence of primary
      resistance was 5.0%, 0.7%, 0.4% and 0% for isoniazid, streptomycin, rifampicin
      and ethambutol respectively. One isolate (0.4%) was MDR, with resistance to
      isoniazid, streptomycin and rifampicin. CONCLUSION: M. Tb primary resistance rate
      in a selected population in Dar es Salaam Tanzania is low and efforts should be
      undertaken to support the Tuberculosis program.

PMID- 18710512
TI  - Skateboards: are they really perilous? a retrospective study from a district
      hospital.
AB  - BACKGROUND: Skateboarding has been a popular sport among teenagers even with its
      attendant associated risks. The literature is packed with articles regarding the
      perils of skateboards. Is the skateboard as dangerous as has been portrayed?
      METHODS: This was a retrospective study conducted over a 5 year period. All
      skateboard related injuries seen in the Orthopaedic unit were identified and data
      collated on patient demographics, mechanism & location of injury, annual
      incidence, type of injury, treatment needed including hospitalisation. RESULTS:
      We encountered 50 patients with skateboard related injuries. Most patients were
      males and under the age of 15. The annual incidence has remained low at about 10.
      The upper limb was predominantly involved with most injuries being fractures.
      Most injuries occurred during summer. The commonest treatment modality was
      plaster immobilisation. The distal radius was the commonest bone to be fractured.
      There were no head & neck injuries, open fractures or injuries requiring surgical
      intervention. CONCLUSION: Despite its negative image among the medical
      fraternity, the skateboard does not appear to be a dangerous sport with a low
      incidence and injuries encountered being not severe. Skateboarding should be
      restricted to supervised skateboard parks and skateboarders should wear
      protective gear. These measures would reduce the number of skateboarders injured
      in motor vehicle collisions, reduce the personal injuries among skateboarders,
      and reduce the number of pedestrians injured in collisions with skateboarders.

PMID- 18710513
TI  - Meta-analysis of SUMO1.
AB  - An abundantly growing body of literature implicates conjugation of SUMO in the
      regulation of many proteins and processes, yet the regulation of SUMO pathways is
      poorly understood. To gain insight into the players in the SUMO1 pathway I have
      performed an in-silico co-expression meta-analysis of SUMO1, comparing many
      different multi-microarray studies of various normal and human tumour tissues,
      from the Oncomine database. This serves as a data-driven predictor of pathway
      partners of SUMO1. While the data obtained need to be confirmed by future
      independent experiments and can currently only be considered a hypothesis,
      results implicate defender against cell death (DAD1) and the anti-apoptotic DEK
      oncogene as new pathway partners of SUMO1.

PMID- 18710514
TI  - The complete chloroplast genome sequence of Brachypodium distachyon: sequence
      comparison and phylogenetic analysis of eight grass plastomes.
AB  - BACKGROUND: Wheat, barley, and rye, of tribe Triticeae in the Poaceae, are among
      the most important crops worldwide but they present many challenges to genomics
      aided crop improvement. Brachypodium distachyon, a close relative of those
      cereals has recently emerged as a model for grass functional genomics. Sequencing
      of the nuclear and organelle genomes of Brachypodium is one of the first steps
      towards making this species available as a tool for researchers interested in
      cereals biology. FINDINGS: The chloroplast genome of Brachypodium distachyon was
      sequenced by a combinational approach using BAC end and shotgun sequences derived
      from a selected BAC containing the entire chloroplast genome. Comparative
      analysis indicated that the chloroplast genome is conserved in gene number and
      organization with respect to those of other cereals. However, several
      Brachypodium genes evolve at a faster rate than those in other grasses. Sequence
      analysis reveals that rice and wheat have a ~2.1 kb deletion in their plastid
      genomes and this deletion must have occurred independently in both species.
      CONCLUSION: We demonstrate that BAC libraries can be used to sequence plastid,
      and likely other organellar, genomes. As expected, the Brachypodium chloroplast
      genome is very similar to those of other sequenced grasses. The phylogenetic
      analyses and the pattern of insertions and deletions in the chloroplast genome
      confirmed that Brachypodium is a close relative of the tribe Triticeae.
      Nevertheless, we show that some large indels can arise multiple times and may
      confound phylogenetic reconstruction.

PMID- 18710515
TI  - Are residential and nursing homes adequately screening overseas healthcare
      workers?
AB  - BACKGROUND: There has been significant growth in the number of healthcare workers
      born outside the UK or recruited to the UK from countries with a high prevalence
      of TB, Hepatitis and other blood borne infections. Government policy recognises
      the need for occupational health procedures to facilitate treatment for these
      individuals and to reduce the risk of transmission of disease to patients.The aim
      of this study was to undertake a survey of nursing and residential homes in South
      East England, to assess whether homes had occupational health screening policies
      for healthcare workers who have originated from overseas, and what level of
      occupational health screening had been undertaken on these employees. METHODS: An
      anonymous survey was sent to all 500 homes in West Sussex assessing occupational
      health practices for "overseas health care workers", defined as health care
      workers who had been born outside the UK. RESULTS: Only one employer (0.8%)
      reported they had an occupational health screening policy specific for healthcare
      workers who originate from overseas. Over 80% of homes who had recruited directly
      had no evidence of screening results for HIV, TB, Hepatitis B and C. The
      commonest countries of origin for staff were the UK, Philippines, Poland, South
      Africa, Zimbabwe, and India. CONCLUSION: This study suggests that screening of
      overseas healthcare workers is not routine practice for residential or nursing
      care homes and requires further input from Primary Care Trust's, Health Care
      Commission, Commission for Social Care Inspection, and Professional bodies.

PMID- 18710516
TI  - SigWin-detector: a Grid-enabled workflow for discovering enriched windows of
      genomic features related to DNA sequences.
AB  - BACKGROUND: Chromosome location is often used as a scaffold to organize genomic
      information in both the living cell and molecular biological research. Thus, ever
      increasing amounts of data about genomic features are stored in public databases
      and can be readily visualized by genome browsers. To perform in silico
      experimentation conveniently with this genomics data, biologists need tools to
      process and compare datasets routinely and explore the obtained results
      interactively. The complexity of such experimentation requires these tools to be
      based on an e-Science approach, hence generic, modular, and reusable. A virtual
      laboratory environment with workflows, workflow management systems, and Grid
      computation are therefore essential. FINDINGS: Here we apply an e-Science
      approach to develop SigWin-detector, a workflow-based tool that can detect
      significantly enriched windows of (genomic) features in a (DNA) sequence in a
      fast and reproducible way. For proof-of-principle, we utilize a biological use
      case to detect regions of increased and decreased gene expression (RIDGEs and
      anti-RIDGEs) in human transcriptome maps. We improved the original method for
      RIDGE detection by replacing the costly step of estimation by random sampling
      with a faster analytical formula for computing the distribution of the null
      hypothesis being tested and by developing a new algorithm for computing moving
      medians. SigWin-detector was developed using the WS-VLAM workflow management
      system and consists of several reusable modules that are linked together in a
      basic workflow. The configuration of this basic workflow can be adapted to
      satisfy the requirements of the specific in silico experiment. CONCLUSION: As we
      show with the results from analyses in the biological use case on RIDGEs, SigWin
      detector is an efficient and reusable Grid-based tool for discovering windows
      enriched for features of a particular type in any sequence of values. Thus,
      SigWin-detector provides the proof-of-principle for the modular e-Science based
      concept of integrative bioinformatics experimentation.

PMID- 18710517
TI  - Streptococcus pneumoniae early response genes to human lung epithelial cells.
AB  - BACKGROUND: Streptococcus pneumoniae infection starts from colonization of the
      host respiratory tract where interaction with host respiratory tract epithelial
      cells occurs. To investigate pneumococcal genes that are involved in the early
      stage of interaction with host epithelial cells, transcriptional responses of an
      encapsulated pathogenic pneumococcal strain TIGR4 upon exposure to human lung
      epithelial cells A549 for 0.5 h and 1 h time periods were investigated by using
      TIGR (JCVI) microarray technology. Gene expression changes were validated by
      quantitative real-time PCR (qRT-PCR) analysis. FINDINGS: We observed different
      transcriptional profiles at two incubation time periods in which most gene
      expressions were down-regulated at 0.5 h but up-regulated at 1 h. Many genes
      associated with ribonucleotide biosynthesis were down-regulated at both time
      points, whereas the genes associated with cell envelope, energy metabolism,
      transport and protein synthesis were mostly up-regulated at 1 h. Furthermore,
      these profiles were compared to the transcriptomes of a TIGR4-derived strain in
      response to human macrophages for the same time periods. We found one set of
      genes that exhibited similar expression changes upon exposure to both types of
      host cells, including cell envelope-associated bgaA (SP0648) and nanA (SP1693),
      and uncharacterized gene clusters such as SP1677-SP1680 and SP1688-SP1690.
      CONCLUSION: These data indicate that at the early stage of interaction with host
      epithelial cells, a complex gene regulation and expression change occur in
      bacteria. Some of them might play an essential role during pathogen-host
      interactions and for the establishment of infection.

PMID- 18710518
TI  - Power of grammatical evolution neural networks to detect gene-gene interactions
      in the presence of error.
AB  - BACKGROUND: With the advent of increasingly efficient means to obtain genetic
      information, a great insurgence of data has resulted, leading to the need for
      methods for analyzing this data beyond that of traditional parametric statistical
      approaches. Recently we introduced Grammatical Evolution Neural Network (GENN), a
      machine-learning approach to detect gene-gene or gene-environment interactions,
      also known as epistasis, in high dimensional genetic epidemiological data. GENN
      has been shown to be highly successful in a range of simulated data, but the
      impact of error common to real data is unknown. In the current study, we examine
      the power of GENN to detect interesting interactions in the presence of noise due
      to genotyping error, missing data, phenocopy, and genetic heterogeneity.
      Additionally, we compare the performance of GENN to that of another computational
      method - Multifactor Dimensionality Reduction (MDR). FINDINGS: GENN is extremely
      robust to missing data and genotyping error. Phenocopy in a dataset reduces the
      power of both GENN and MDR. GENN is reasonably robust to genetic heterogeneity
      and find that in some cases GENN has substantially higher power than MDR to
      detect functional loci in the presence of genetic heterogeneity. CONCLUSION: GENN
      is a promising method to detect gene-gene interaction, even in the presence of
      common types of error found in real data.

PMID- 18710519
TI  - Required muscle mass for preventing lifestyle-related diseases in Japanese women.
AB  - BACKGROUND: Since it is essential to maintain a high level of cardiorespiratory
      fitness to prevent life-style related disease, the Ministry of Health, Labour and
      Welfare of Japan in 2006 proposed to determine the maximal oxygen uptake (Vo2max:
      mL.kg-1.min-1) reference values to prevent life-style related diseases (LSRD).
      Since muscle mass is one of the determinant factors of Vo2max, it could be used
      as the reference parameter for preventing LSRD. The aim of this study was to
      determine and quantify the muscle mass required to maintain the Vo2max reference
      values in Japanese women. METHODS: A total of 403 Japanese women aged 20-69 years
      were randomly allocated to either a validation or a cross-validation group. In
      the validation group, a multiple regression equation, which used a set of age and
      the percentage of muscle mass (%MM, percentage of appendicular lean soft tissue
      mass to body weight), as independent variables, was derived to estimate the
      Vo2max. After the equation was cross-validated, data from the two groups were
      pooled together to establish the final equation. The required %MM for each
      subject was recalculated by substituting the Vo2max reference values and her age
      in the final equation. RESULTS: The mean value of required %MM was identified as
      (28.5 +/- 0.35%). Thus, the present study proposed the required muscle mass
      (28.5% per body weight) in Japanese women to maintain the Vo2max reference values
      determined by the Japanese Ministry of Health Labour and Welfare. CONCLUSION: The
      estimated required %MM (28.5% per body weight) can be used as one of the
      reference parameters of fitness level in Japanese women.

PMID- 18710520
TI  - The effect of low-dye taping on rearfoot motion and plantar pressure during the
      stance phase of gait.
AB  - BACKGROUND: Low-dye (LD) taping is commonly used to reduce rearfoot pronation. No
      studies have previously investigated the effectiveness of LD taping using both
      plantar pressure distribution (F-Scan) and 3-D (CODA) analysis of rearfoot
      motion. METHODS: 20 healthy subjects with a navicular drop test exceeding 10 mm
      participated in the study. T tests were used to determine whether significant (p
      < 0.05) differences in plantar pressure and rearfoot motion occurred with LD
      taping. RESULTS: LD taping resulted in statistically significant increases in
      peak plantar pressure in the lateral midfoot (p = 0.000), along with significant
      decreases in pressure in the medial forefoot (p = 0.014), and the medial (p =
      0.000) and lateral hindfoot (p = 0.007). No significant changes occurred in the
      medial midfoot (p = 0.794) or lateral forefoot (p = 0.654). When assessed using
      motion analysis, taping resulted in a statistically significant decrease in
      rearfoot pronation (p = 0.006), supination (p = 0.025) and total rearfoot range
      of motion (p = 0.000). The mean rearfoot position during stance was not
      significantly different however (p = 0.188). CONCLUSION: LD taping is associated
      with alterations in peak plantar pressure in the midfoot and forefoot that
      indicate reduced pronation with LD taping. However, LD taping appears to reduce
      both pronation and supination in the rearfoot, rather than simply reducing
      pronation, when assessed using 3D motion analysis. Therefore, it would appear
      that LD taping does indeed reduce pronation, by restricting rearfoot motion in
      general, rather than pronation specifically. The degree of change observed with
      LD taping was however very small, and further research is needed to clarify the
      clinical significance of these initial findings.

PMID- 18710521
TI  - Hyponatremia and hospital outcomes among patients with pneumonia: a retrospective
      cohort study.
AB  - BACKGROUND: Community-acquired (CAP) and nosocomial pneumonias contribute
      substantially to morbidity and hospital resource utilization. Hyponatremia,
      occurring in >1/4 of patients with CAP, is associated with greater disease
      severity and worsened outcomes. METHODS: To explore how hyponatremia is
      associated with outcomes in hospitalized patients with pneumonia, we analyzed a
      large administrative database with laboratory component from January 2004 to
      December 2005. Hyponatremia was defined as at least two [Na+] < 135 mEq/L within
      24 hours of admission value. RESULTS: Of 7,965 patients with pneumonia, 649
      (8.1%) with hyponatremia were older (72.4 +/- 15.7 vs. 68.0 +/- 22.0, p < 0.01),
      had a higher mean Deyo-Charlson Comorbidity Index Score (1.7 +/- 1.7 vs. 1.6 +/-
      1.6, p = 0.02), and higher rates of ICU (10.0% vs. 6.3%, p < 0.001) and MV (3.9%
      vs. 2.3%, p = 0.01) in the first 48 hours of hospitalization than patients with
      normal sodium. Hyponatremia was associated with an increased ICU (6.3 +/- 5.6 vs.
      5.3 +/- 5.1 days, p = 0.07) and hospital lengths of stay (LOS, 7.6 +/- 5.3 vs.
      7.0 +/- 5.2 days, p < 0.001) and a trend toward increased hospital mortality
      (5.4% vs. 4.0%, p = 0.1). After adjusting for confounders, hyponatremia was
      associated with an increased risk of ICU (OR 1.58, 95% CI 1.20-2.08), MV (OR 1.75
      95% CI 1.13-2.69), and hospital death (OR 1.3, 95% CI 0.90-1.87) and with
      increases of 0.8 day to ICU and 0.3 day to hospital LOS, and over $1,300 to total
      hospital costs. CONCLUSION: Hyponatremia is common among hospitalized patients
      with pneumonia and is associated with worsened clinical and economic outcomes.
      Studies in this large population are needed to explore whether prompt correction
      of [Na+] may impact these outcomes.

PMID- 18710522
TI  - Is it possible to identify patient's sex when reading blinded illness narratives?
      An experimental study about gender bias.
AB  - BACKGROUND: In many diseases men and women, for no apparent medical reason, are
      not offered the same investigations and treatment in health care. This may be due
      to staff's stereotypical preconceptions about men and women, i.e., gender bias.
      In the clinical situation it is difficult to know whether gender differences in
      management reflect physicians' gender bias or male and female patients' different
      needs or different ways of expressing their needs. To shed some light on these
      possibilities this study investigated to what extent it was possible to identify
      patients' sex when reading their blinded illness narratives, i.e., do male and
      female patients express themselves differently enough to be recognised as men and
      women without being categorised on beforehand? METHODS: Eighty-one authentic
      letters about being diseased by cancer were blinded regarding sex and read by 130
      students of medicine and psychology. For each letter the participants were asked
      to give the author's sex and to explain their choice. The success rates were
      analysed statistically. To illuminate the participants' reasoning the
      explanations of four letters were analysed qualitatively. RESULTS: The patient's
      sex was correctly identified in 62% of the cases, with significantly higher rates
      in male narratives. There were no differences between male and female
      participants. In the qualitative analysis the choice of a male writer was
      explained by: a short letter; formal language; a focus on facts and a lack of
      emotions. In contrast the reasons for the choice of a woman were: a long letter;
      vivid language; mention of emotions and interpersonal relationships. Furthermore,
      the same expressions were interpreted differently depending on whether the
      participant believed the writer to be male or female. CONCLUSION: It was possible
      to detect gender differences in the blinded illness narratives. The students'
      explanations for their choice of sex agreed with common gender stereotypes
      implying that such stereotypes correspond, at least on a group level, to
      differences in male and female patients' illness descriptions. However, it was
      also obvious that preconceptions about gender obstructed and biased the
      interpretations, a finding with implications for the understanding of gender bias
      in clinical practice.

PMID- 18710523
TI  - Hyperosmotic stress enhances cytokine production and decreases phagocytosis in
      vitro.
AB  - INTRODUCTION: Hyperglycemia is associated with negative outcomes in various
      settings of critical illness; infectious complications, especially, seem to be
      increased. On the other hand, intensive insulin therapy (IIT) has been shown to
      improve outcome in clinical trials. Whether normoglycemia itself or the
      application of insulin is responsible for the observed findings is unknown. We
      therefore tested the effect of glucose and insulin on various immune functions in
      vitro. METHODS: Human peripheral blood mononuclear cells (PBMCs) were incubated
      ex vivo with low doses of lipopolysaccharide (LPS). PBMCs were incubated with
      various osmotic agents, insulin, or a combination of both. Interleukin (IL)-6 and
      IL-1 cytokine response was measured by enzyme-linked immunosorbent assay. In
      addition, we investigated the effects of glucose on phagocytosis and oxidative
      burst in human granulocytes. RESULTS: Increasing concentrations of both glucose
      and mannitol significantly enhanced LPS-induced cytokine production. Insulin
      alone did not alter cytokine production and had only a minor influence in
      combination with glucose. Phagocytosis and oxidative burst were significantly
      reduced with increasing concentrations of glucose and mannitol. CONCLUSION:
      Hyperglycemia may lead to inflammation by enhancing cytokine production via the
      direct effects of hyperosmotic stress. Impaired phagocytosis and oxidative burst
      under hyperglycemia may weaken defense mechanisms of the host. Our in vitro
      findings may help to explain the beneficial effects of IIT not only in diabetic
      but also in critically ill patients.

PMID- 18710524
TI  - Is there a divide between local medicinal knowledge and Western medicine? a case
      study among native Amazonians in Bolivia.
AB  - BACKGROUND: Interest in ethnomedicine has grown in the last decades, with much
      research focusing on how local medicinal knowledge can contribute to Western
      medicine. Researchers have emphasized the divide between practices used by local
      medical practitioners and Western doctors. However, researchers have also
      suggested that merging concepts and practices from local medicinal knowledge and
      Western science have the potential to improve public health and support medical
      independence of local people. In this article we study the relations between
      local and Western medicinal knowledge within a native Amazonian population, the
      Tsimane'. METHODS: We used the following methods: 1) participant observation and
      semi-structured interviews to gather background information, 2) free-listing and
      pile-sorting to assess whether Tsimane' integrate local medicinal knowledge and
      Western medicine at the conceptual level, 3) surveys to assess to what extent
      Tsimane' combine local medicinal knowledge with Western medicine in actual
      treatments, and 4) a participatory workshop to assess the willingness of Tsimane'
      and Western medical specialists to cooperate with each other. RESULTS: We found
      that when asked about medical treatments, Tsimane' do not include Western
      treatments in their lists, however on their daily practices, Tsimane' do use
      Western treatments in combination with ethnomedical treatments. We also found
      that Tsimane' healers and Western doctors express willingness to cooperate with
      each other and to promote synergy between local and Western medical systems.
      CONCLUSION: Our findings contrast with previous research emphasizing the divide
      between local medical practitioners and Western doctors and suggests that
      cooperation between both health systems might be possible.

PMID- 18710525
TI  - Normalisation genes for expression analyses in the brown alga model Ectocarpus
      siliculosus.
AB  - BACKGROUND: Brown algae are plant multi-cellular organisms occupying most of the
      world coasts and are essential actors in the constitution of ecological niches at
      the shoreline. Ectocarpus siliculosus is an emerging model for brown algal
      research. Its genome has been sequenced, and several tools are being developed to
      perform analyses at different levels of cell organization, including
      transcriptomic expression analyses. Several topics, including physiological
      responses to osmotic stress and to exposure to contaminants and solvents are
      being studied in order to better understand the adaptive capacity of brown algae
      to pollution and environmental changes. A series of genes that can be used to
      normalise expression analyses is required for these studies. RESULTS: We
      monitored the expression of 13 genes under 21 different culture conditions. These
      included genes encoding proteins and factors involved in protein translation
      (ribosomal protein 26S, EF1alpha, IF2A, IF4E) and protein degradation (ubiquitin,
      ubiquitin conjugating enzyme) or folding (cyclophilin), and proteins involved in
      both the structure of the cytoskeleton (tubulin alpha, actin, actin-related
      proteins) and its trafficking function (dynein), as well as a protein implicated
      in carbon metabolism (glucose 6-phosphate dehydrogenase). The stability of their
      expression level was assessed using the Ct range, and by applying both the geNorm
      and the Normfinder principles of calculation. CONCLUSION: Comparisons of the data
      obtained with the three methods of calculation indicated that EF1alpha (EF1a) was
      the best reference gene for normalisation. The normalisation factor should be
      calculated with at least two genes, alpha tubulin, ubiquitin-conjugating enzyme
      or actin-related proteins being good partners of EF1a. Our results exclude actin
      as a good normalisation gene, and, in this, are in agreement with previous
      studies in other organisms.

PMID- 18710527
TI  - Successful outcome of Langerhans cell histiocytosis complicated by therapy
      related myelodysplasia and acute myeloid leukemia: a case report.
AB  - BACKGROUND: Various therapeutic options are available for the management of
      Langerhans cell histiocytosis. However, treatment administered to control this
      disease may be complicated by acute leukemia. CASE PRESENTATION: A 34 years old
      male was diagnosed to have Langerhans cell histiocytosis in March 1999.
      Unfortunately, the cytotoxic chemotherapy and radiotherapy given to control the
      repeated relapses and exacerbations of the primary disease predisposed him to
      therapy-induced myelodysplastic syndrome which transformed into acute myeloid
      leukemia. After achieving complete remission of his leukemia, the patient
      received an allogeneic hematopoietic stem cell transplant. The allograft was
      complicated by chronic graft versus host disease that was controlled by various
      immunosuppressive agents and extracorporal photophoresis. CONCLUSION: Management
      of complicated cases of histiocytosis requires various therapeutic modalities and
      a multidisciplinary approach. Having complications of therapy eg myelodysplasia
      or acute leukemia make the outcome more dismal and the management options limited
      to aggressive forms of treatment. High dose chemotherapy followed by an allograft
      may be a curative option not only for therapy-related myelodysplasia/acute
      leukemia, but also for frequently relapsing and poorly controlled Langerhans cell
      histiocytosis.

PMID- 18710526
TI  - Integrative analyses of genetic variation in enzyme activities of primary
      carbohydrate metabolism reveal distinct modes of regulation in Arabidopsis
      thaliana.
AB  - BACKGROUND: Plant primary carbohydrate metabolism is complex and flexible, and is
      regulated at many levels. Changes of transcript levels do not always lead to
      changes in enzyme activities, and these do not always affect metabolite levels
      and fluxes. To analyze interactions between these three levels of function, we
      have performed parallel genetic analyses of 15 enzyme activities involved in
      primary carbohydrate metabolism, transcript levels for their encoding structural
      genes, and a set of relevant metabolites. Quantitative analyses of each trait
      were performed in the Arabidopsis thaliana Ler x Cvi recombinant inbred line
      (RIL) population and subjected to correlation and quantitative trait locus (QTL)
      analysis. RESULTS: Traits affecting primary metabolism were often correlated,
      possibly due to developmental control affecting multiple genes, enzymes, or
      metabolites. Moreover, the activity QTLs of several enzymes co-localized with the
      expression QTLs (eQTLs) of their structural genes, or with metabolite
      accumulation QTLs of their substrates or products. In addition, many trait
      specific QTLs were identified, revealing that there is also specific regulation
      of individual metabolic traits. Regulation of enzyme activities often occurred
      through multiple loci, involving both cis- and trans-acting transcriptional or
      post-transcriptional control of structural genes, as well as independently of the
      structural genes. CONCLUSION: Future studies of the regulatory processes in
      primary carbohydrate metabolism will benefit from an integrative genetic analysis
      of gene transcription, enzyme activity, and metabolite content. The multiparallel
      QTL analyses of the various interconnected transducers of biological information
      flow, described here for the first time, can assist in determining the causes and
      consequences of genetic regulation at different levels of complex biological
      systems.

PMID- 18710528
TI  - SPECT/CT-plethysmography--non-invasive quantitation of bone and soft tissue blood
      flow.
AB  - Preserved blood flow to bone and soft tissue is essential for their normal
      function. To date only numerous methods are suitable for direct bone blood flow
      (BBF) measurement. Here, we introduce a novel quantitative method for bone and
      soft tissue blood flow (BBF and SBF, respectively) measurement. It involves a
      combination of SPECT/CT imaging for blood pool localization in a specific region
      of interest ("soft" and "hard" tissues composing a limb) with veno-occlusive
      plethysmography. Using it, we measured BBF and SBF in the four limbs of 10
      healthy subjects. At steady state blood flow measurements in the four limbs were
      similar, ranging between 5.5-6.5 and 1.87-2.48 ml per 100 ml of tissue per minute
      for BBF and SBF, respectively. Our results are comparable to those in the
      literature. We concluded that SPECT/CT-plethysmography appears to be a readily
      available and easy to use method to measure BBF and SBF, and can be added to the
      armamentarium of methods for BBF measurements.

PMID- 18710529
TI  - Reductive stress on life span extension in C. elegans.
AB  - Recently, Schulz and colleagues have contributed to the ongoing controversy on
      the unproven role of oxidative stress in the aging process in their well
      performed study 'Glucose restriction extends Caenorhabditis elegans life span by
      inducing mitochondrial respiration and increasing oxidative stress' (Cell Metab
      2007, 6: 280-293). Here, we suggest an alternative hypothesis that reductive
      stress can prevent calorie-restriction induced life span extension. We draw
      attention to this condition as an explanation for some contradictory observations
      including the deleterious effects from antioxidants.

PMID- 18710530
TI  - Fast comparison of DNA sequences by oligonucleotide profiling.
AB  - BACKGROUND: The comparison of DNA sequences is a traditional problem in genomics
      and bioinformatics. Many new opportunities emerge due to the improvement of
      personal computers, allowing the implementation of novel strategies of analysis.
      FINDINGS: We describe a new program, called UVWORD, which determines the number
      of times that each DNA word present in a sequence (target) is found in a second
      sequence (source), a procedure that we have called oligonucleotide profiling. On
      a standard computer, the user may search for words of a size ranging from k = 1
      to k = 14 nucleotides. Average counts for groups of contiguous words may also be
      established. The rate of analysis on standard computers is from 3.4 (k = 14) to
      16 millions of words per second (1 </= k </= 8). This makes feasible the fast
      screening of even the longest known DNA molecules. DISCUSSION: We show that the
      combination of the ability of analyzing words of relatively long size, which
      occur very rarely by chance, and the fast speed of the program allows to perform
      novel types of screenings, complementary to those provided by standard programs
      such as BLAST. This method can be used to determine oligonucleotide content, to
      characterize the distribution of repetitive sequences in chromosomes, to
      determine the evolutionary conservation of sequences in different species, to
      establish regions of similar DNA among chromosomes or genomes, etc.

PMID- 18710531
TI  - Survival of Burkholderia pseudomallei in water.
AB  - BACKGROUND: The ability of Burkholderia pseudomallei to survive in water likely
      contributes to its environmental persistence in endemic regions. To determine the
      physiological adaptations which allow B. pseudomallei to survive in aqueous
      environments, we performed microarray analyses of B. pseudomallei cultures
      transferred from Luria broth (LB) to distilled water. FINDINGS: Increased
      expression of a gene encoding for a putative membrane protein (BPSL0721) was
      confirmed using a lux-based transcriptional reporter system, and maximal
      expression was noted at approximately 6 hrs after shifting cells from LB to
      water. A BPSL0721 deficient mutant of B. pseudomallei was able to survive in
      water for at least 90 days indicating that although involved, BPSL0721 was not
      essential for survival. BPSL2961, a gene encoding a putative phosphatidylglycerol
      phosphatase (PGP), was also induced when cells were shifted to water. This gene
      is likely involved in cell membrane biosynthesis. We were unable to construct a
      PGP mutant suggesting that the gene is not only involved in survival in water but
      is essential for cell viability. We also examined mutants of polyhydroxybutyrate
      synthase (phbC), lipopolysaccharide (LPS) oligosaccharide and capsule synthesis,
      and these mutations did not affect survival in water. LPS mutants lacking outer
      core were found to lose viability in water by 200 days indicating that an intact
      LPS core provides an outer membrane architecture which allows prolonged survival
      in water. CONCLUSION: The results from these studies suggest that B. pseudomallei
      survival in water is a complex process that requires an LPS molecule which
      contains an intact core region.

PMID- 18710532
TI  - Absence of mtDNA mutations in leukocytes of CADASIL patients.
AB  - BACKGROUND: Ultrastructural and biochemical abnormalities of mitochondria have
      been reported in skeletal muscle biopsies of CADASIL patients with mutations in
      the NOTCH3 nuclear gene. Additionally, it was proposed that NOTCH3 gene mutations
      may predispose the mitochondrial DNA (mtDNA) to mutations. METHODS: We sequenced
      the entire mitochondrial genome in five Arab patients affected by CADASIL.
      RESULTS: The mean number of mtDNA sequence variants (synonymous and
      nonsynonymous) in CADASIL patients was not statistically significantly different
      from that in controls (p = 0.378). After excluding haplogroup specific single
      nucleotide polymorphisms (SNPs) and proved silent polymorphisms, no known or
      novel pathologic mtDNA mutation(s) could be detected in any patient.
      Additionally, there was no difference in the prevalence of different
      mitochondrial haplogroups between patients and controls. CONCLUSION: Our study
      group is too small for any valid conclusion to be made. However, if our
      observation is confirmed in larger study group, then mtDNA mutations or
      mitochondrial haplogroups may not be important in the pathogenesis of CADASIL.

PMID- 18710533
TI  - Interaction of the growth and tumour suppressor NORE1A with microtubules is not
      required for its growth-suppressive function.
AB  - BACKGROUND: The NORE1 protein was identified in a yeast two-hybrid screen as a
      Ras effector that binds Ras protein in a GTP-dependent manner. NORE1A is a growth
      and tumour suppressor that is inactivated in a variety of cancers. In transformed
      human cells, both full-length NORE1A protein and its effector domain alone (amino
      acids 191-363) are localized to microtubules and centrosomes. However, the
      mechanism by which NORE1A associates with these cytoskeletal elements is not
      known; furthermore, whether centrosomally-associated or microtubule-associated
      NORE1A suppresses tumour cell growth has not been yet established. FINDINGS: We
      have shown that purified NORE1A fails to bind to microtubules in vitro suggesting
      that other protein(s) mediate NORE1A-microtubule association. Using mass
      spectrometry, we identified the Microtubule-Associated Protein 1B (MAP1B) and its
      homologue C19ORF5 as NORE1A interaction partners. Suppression of C19ORF5
      expression by RNA interference (RNAi) and immunodepletion of C19ORF5 protein from
      cell extracts showed that binding of NORE1A to microtubules is not dependent on
      C19ORF5. Conversely, RNAi suppression of MAP1B revealed that MAP1B is required
      for association of NORE1A with microtubules. RNAi-mediated depletion of C19ORF5
      or MAP1B did not prevent centrosomal localization of NORE1A. Moreover, the
      depletion of C19ORF5 or MAP1B did not prevent NORE1A's ability to suppress tumour
      cell growth. CONCLUSION: The interaction of NORE1A with microtubules is mediated
      by MAP1B, but not C19ORF5 protein. Interaction of NORE1A with centrosomes is not
      dependent on C19ORF5 or MAP1B, and appears to involve a different mechanism
      independent of binding to microtubules. The NORE1A microtubular localization is
      not required for growth suppression.

PMID- 18710534
TI  - Inappropriately low aldosterone concentrations in adults with AIDS-related
      diarrhoea in Zambia: a study of response to fluid challenge.
AB  - BACKGROUND: Chronic diarrhoea is one of the most debilitating consequences of HIV
      infection in sub-Saharan Africa and it carries a high mortality rate. We report
      unexpectedly low concentrations of circulating aldosterone in 12 patients (6 men,
      6 women) in the University Teaching Hospital, Lusaka, who all had diarrhoea for
      over one month. Changes in serum electrolytes, blood pressure, Karnofsky score
      and serum aldosterone concentration were being monitored during a short study of
      responses to saline infusion (3 litres/24 h) over 72 hours. FINDINGS: At
      baseline, 9/12 (75%) of the patients were hyponatraemic, 10/11 (91%) were
      hypokalaemic, and 6/12 (50%) had undetectable aldosterone concentrations. Blood
      pressure and Karnofsky score rose and creatinine concentration fell in response
      to the infusion. CONCLUSION: Circulating aldosterone concentrations were
      inappropriately low and complicate the profound electrolyte deficiencies
      resulting from chronic diarrhoea. Management of these deficiencies needs to be
      more aggressive than is currently practised and consideration should be given to
      a formal clinical trial of mineralocorticoid replacement in these severely ill
      patients. If the inappropriately low aldosterone reflects a general adrenal
      failure, it may explain a considerable proportion of the high mortality seen both
      before and after initiation of anti-retroviral therapy.

PMID- 18710535
TI  - Brain region-specificity of palmitic acid-induced abnormalities associated with
      Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is a progressive, neurodegenerative disease
      mostly affecting the basal forebrain, cortex and hippocampus whereas the
      cerebellum is relatively spared. The reason behind this region-specific brain
      damage in AD is not well understood. Here, we report our data suggesting
      "differential free fatty acid metabolism in the different brain areas" as a
      potentially important factor in causing the region-specific damage observed in AD
      brain. FINDINGS: The astroglia from two different rat brain regions, cortex
      (region affected in AD) and cerebellum (unaffected region), were treated with 0.2
      mM of palmitic acid. The conditioned media were then transferred to the cortical
      neurons to study the possible effects on the two main, AD-associated protein
      abnormalities, viz. BACE1 upregulation and hyperphosphorylation of tau. The
      conditioned media from palmitic-acid treated cortical astroglia, but not the
      cerebellar astroglia, significantly elevated levels of phosphorylated tau and
      BACE1 in cortical neurons as compared to controls (47 +/- 7% and 45 +/- 4%,
      respectively). CONCLUSION: The present data provide an experimental explanation
      for the region-specific damage observed in AD brain; higher fatty acid
      metabolizing capacity of cortical astroglia as compared to cerebellar astroglia,
      may play a causal role in increasing vulnerability of cortex in AD, while sparing
      cerebellum.

PMID- 18710536
TI  - Heminested reverse-transcriptase polymerase chain reaction (hnRT-PCR) as a tool
      for rabies virus detection in stored and decomposed samples.
AB  - BACKGROUND: The use of methods, both sensitive and specific, for rabies diagnosis
      are important tools for the control and prophylaxis of the disease. Reverse
      Transcriptase Polymerase Chain Reaction (RT-PCR) has been used in rabies
      diagnosis with good results, even in decomposed materials. Additionally,
      molecular techniques have been used for epidemiological studies and to gain a
      better knowledge of viral epidemiology. FINDINGS: The aim of this work was to
      evaluate the RT-PCR and hnRT-PCR for rabies virus detection in original tissues
      stored at -20 degrees C for different periods considering their use for rabies
      virus detection in stored and decomposed samples. RT-PCR and hnRT-PCR were
      evaluated in 151 brain samples from different animal species, thawed and left at
      room temperature for 72 hours for decomposition.The RT-PCR and hnRT-PCR results
      were compared with previous results from Direct Fluorescent Antibody Test and
      Mouse Inoculation Test. From the 50 positive fresh samples, 26 (52%) were
      positive for RT-PCR and 45 (90%) for hnRT-PCR. From the 48 positive decomposed
      samples, 17 (34, 3%) were positive for RT-PCR and 36 (75%) for hnRT-PCR. No false
      positives results were found in the negatives samples evaluated to the molecular
      techniques. CONCLUSION: These results show that the hnRT-PCR was more sensitive
      than RT-PCR, and both techniques presented lower sensibility in decomposed
      samples. The hnRT-PCR demonstrated efficacy in rabies virus detection in stored
      and decomposed materials suggesting it's application for rabies virus
      retrospective epidemiological studies.

PMID- 18710537
TI  - Comparison of palpation-versus ultrasound-guided fine-needle aspiration biopsies
      in the evaluation of thyroid nodules.
AB  - BACKGROUND: The aim of this study was to compare the results of palpation-versus
      ultrasound-guided thyroid fine-needle aspiration (FNA) biopsies. FINDINGS:
      Clinical data, cytology and histopathology results were retrospectively analyzed
      on all patients who underwent thyroid FNA biopsy in our outpatient endocrinology
      clinic between January 1998 and April 2003. The same investigators performed all
      thyroid FNAs (ASC) and cytological evaluations (KP). Subjects in the ultrasound
      guided group were older, otherwise there were no differences in baseline
      characteristics (gender, thyroid function, the frequency of multinodular goiter,
      nodule diameter and nodule location) between groups. Cytology results in nodules
      aspirated by palpation (n = 202) versus ultrasound guidance (n = 184) were as
      follows: malignant 2.0% versus 2.7% (p = 0.74), benign 69.8% versus 79.9% (p =
      0.02), indeterminate 1.0% versus 4.9% (p = 0.02), inadequate 27.2% versus 12.5%
      (p < 0.01). Malignant results were compared with Fisher's exact test. Other
      cytology categories were compared with chi-square test. Eighteen patients from
      the palpation- and 23 from ultrasound-guided group underwent surgery. In the
      palpation-guided group, the sensitivity of FNA was 100%, specificity 94%,
      positive predictive value 67% and negative predictive value 100%. In the
      ultrasound-guided group, the sensitivity of FNA was 100%, specificity 80%,
      positive predictive value 73% and negative predictive value 100%. CONCLUSION: We
      demonstrate that ultrasound guidance for thyroid FNA significantly decreases
      inadequate for evaluation category. We also confirm the high sensitivity and
      specificity of thyroid FNA biopsy in the diagnosis of thyroid cancer. Where
      available, we recommend universal application of ultrasound guidance for thyroid
      FNA biopsy as a standard component of this diagnostic technique.

PMID- 18710538
TI  - Prevalence of malnutrition among settled pastoral Fulani children in Southwest
      Nigeria.
AB  - BACKGROUND: There is a dearth of information on the health of pastoral Fulani
      children living in southwestern Nigeria. These are fully settled pastoralists
      whose economy are centred on cattle and farming. In other to monitor and plan
      appropriate nutritional intervention for their children, a cross-sectional study
      was carried out to determine the prevalence of malnutrition of pastoral Fulani
      children. FINDINGS: Fulani's children aged 6 months to 15 years, living in 61
      settlements in Kwara, Ogun and Oyo States in Southwestern Nigeria participated in
      the study. Heights and weights of 164 girls and 167 boys were measured. Their
      anthropometric indices, height-for-age (HA), weight-for-height (WH), and weight
      for-age (WA) Z-scores determined. The prevalence of stunting (HAZ < -2), wasting
      (WHZ < -2) and underweight (WAZ < -2) was 38.7%, 13.6%, and 38.7%, respectively
      when compared to the reference NCHS/WHO standard used for defining stunting,
      wasting and underweight. Boys were more malnourished than the girls were, but
      this was not significant (stunting: chi2 = 0.36; df = 1; P = 0.54); (underweight:
      chi2 = 1.10; df = 1; P = 0.29); and (wasting: chi2 = 0.00; df = 1; P = 0.98) The
      mean of Z-scores of Height-for-age, Weight-for-age and Weight-for-height in
      children were -1.502, -1.634 and -0.931 respectively. The SD was 1.52, 1.09 and
      1.20 respectively. Using WHO Malnutrition Classification systems, 38.7% of the
      children were found to be malnourished. CONCLUSION: These results indicate high
      prevalence of malnutrition among settled pastoral Fulani children, possibly due
      to changes in food habits and lifestyle occasion by the transition from nomadic
      to sedentary living. We suggest the inclusion of Fulani's settlements in
      nutritional intervention for these areas.

PMID- 18710539
TI  - Development of a broad-host-range sacB-based vector for unmarked allelic
      exchange.
AB  - BACKGROUND: Although genome sequences are available for an ever-increasing number
      of bacterial species, the availability of facile genetic tools for physiological
      analysis have generally lagged substantially behind traditional genetic models.
      RESULTS: Here I describe the development of an improved, broad-host-range "in
      out" allelic exchange vector, pCM433, which permits the generation of clean,
      marker-free genetic manipulations. Wild-type and mutant alleles were reciprocally
      exchanged at three loci in Methylobacterium extorquens AM1 in order to
      demonstrate the utility of pCM433. CONCLUSION: The broad-host-range vector for
      marker-free allelic exchange described here, pCM433, has the advantages of a high
      copy, general Escherichia coli replicon for easy cloning, an IncP oriT enabling
      conjugal transfer, an extensive set of restriction sites in its polylinker, three
      antibiotic markers, and sacB (encoding levansucrase) for negative selection upon
      sucrose plates. These traits should permit pCM433 to be broadly applied across
      many bacterial taxa for marker-free allelic exchange, which is particularly
      important if multiple manipulations or more subtle genetic manipulations such as
      point mutations are desired.

PMID- 18710540
TI  - Hypertension among adults in a deprived urban area of Peru - undiagnosed and
      uncontrolled?
AB  - BACKGROUND: In Peru, cardiovascular disease was the second most common cause of
      death in those aged 65 years or more in 2000. Hypertension is a major modifiable
      risk factor for cardiovascular disease, and if treated can significantly reduce
      cardiovascular disease risk. The objectives of this study were to investigate the
      prevalence of hypertension and levels of awareness, treatment and control in a
      deprived urban area of Peru. METHODS: A cross-sectional study was completed.
      Blood pressure measurements were recorded in triplicate. Hypertension was defined
      as systolic blood pressure >/= 140 mmHg or diastolic blood pressure >/= 90 mmHg,
      or self report of receiving antihypertensive medication at the time of interview.
      RESULTS: The study sample was 584 adults (29.1% male, mean age 35.3 years). Age
      standardized prevalence of hypertension was 19.5% (95% CI 9.9%, 29.1%) in men,
      11.4% (95% CI 3.7%, 19.1%) in women, and 13.2% (95% CI 5.0%, 21.5%) overall.
      Among those with hypertension 38.3% (95% CI 22.7%, 53.9%, n = 18/47) were aware
      of their condition with greater awareness among women than men. Of those aware,
      61.1% (n = 11/18) were treated, equating to 23.4% (95% CI 10.1%, 36.7%, n =
      11/47) of all adults with hypertension. Of those treated 63.6% (n = 7/11) had
      controlled hypertension, equating to 14.9% (95% CI 3.0%, 26.8%, n = 7/47) of all
      adults with hypertension. CONCLUSION: Levels of awareness and control in this
      population were low. Lack of control is likely to be due to both a failure to
      diagnose hypertension, especially among men, and initiate or comply with
      treatment, especially among women. These results suggest a considerable burden of
      undiagnosed hypertension, and poor levels of control in those treated, in a
      deprived urban area of Lima, Peru.

PMID- 18710541
TI  - Risk-communication capability for public health emergencies varies by community
      diversity.
AB  - BACKGROUND: Public health emergencies heighten several challenges in risk
      communication: providing trustworthy sources of information, reaching
      marginalized populations, and minimizing fear and public confusion. In
      emergencies, however, information may not diffuse equally among all social
      groups, and gaps in knowledge may increase. Such knowledge gaps vary by social
      structure and the size, socioeconomic status, and diversity of the population.
      This study explores the relationship between risk-communication capabilities, as
      perceived by public officials participating in emergency tabletop exercises, and
      community size and diversity. FINDINGS: For each of the three communication
      functions tested, risk-communication capabilities are perceived to be greater in
      communities with fewer then 10% of the population speaking a language other than
      English at home, decreasing as the percentage grows to 20% (ANOVA P </= 0.02).
      With respect to community size, however, we found an N-shaped relationship
      between perceived risk communication capabilities and population size.
      Capabilities are perceived highest in the largest communities and lowest in the
      smallest, but lower in communities with 20,000-49,999 inhabitants compared to
      those with 2,500-19,999. CONCLUSION: The results of this study suggest the need
      to factor population diversity into risk communication plans and the need for
      improved state or regional risk-communication capabilities, especially for
      communities with limited local capacity.

PMID- 18710542
TI  - RNase footprinting demonstrates antigenomic hepatitis delta virus ribozyme
      structural rearrangement as a result of self-cleavage reaction.
AB  - BACKGROUND: Hepatitis delta virus (HDV) is a satellite virus of hepatitis B.
      During viral replication the 1700-nucleotide-long genomic RNA and its complement,
      the antigenomic RNA, undergo self-cleavage catalyzed by internal ribozyme motifs
      that are essential for propagation of the virus in vivo. These self-cleavage
      activities are provided by 85-nucleotide-long sequence elements, the genomic and
      antigenomic forms of HDV ribozyme. Recently four permuted variants of the
      antigenomic HDV cis-ribozyme with a self-cleavage site located at the 5'
      proximity, in the middle, or nearby the 3' end of the molecule were constructed
      and synthesized. These constructs exhibit equal activity, a bi-phasic kinetics of
      self-cleavage reaction and reaction products with low and high stability. We have
      used ribonuclease probing to footprint the structures of uncleaved and post
      cleaved forms of the antigenomic HDV ribozymes in solution. Uncleaved ribozymes,
      associated and individual products of the self-cleavage reaction were analyzed
      using ribonuclease and Fe(II)-EDTA protection assays to reveal the differences in
      the structure of pre- and post-cleaved antigenomic HDV ribozyme in solution.
      FINDINGS: Our findings demonstrate that a significant conformational change
      accompanies catalysis in the antigenomic HDV ribozyme in solution, in contrast to
      minor conformational switch observed in crystals of the genomic form. This study
      indicates that changes in the structure of stem P1 and stem P4 are minor, those
      of the region ascribed to stem P2, stem P3 and loop l3 are dramatic, while stem
      P1.1 results from the self-cleavage reaction. CONCLUSION: Our data agree with the
      structure of post-cleaved and disagree with that of pre-cleaved forms of HDV
      ribozyme published elsewhere.

PMID- 18710543
TI  - Spike-in validation of an Illumina-specific variance-stabilizing transformation.
AB  - BACKGROUND: Variance-stabilizing techniques have been used for some time in the
      analysis of gene expression microarray data. A new adaptation, the variance
      stabilizing transformation (VST), has recently been developed to take advantage
      of the unique features of Illumina BeadArrays. VST has been shown to perform well
      in comparison with the widely-used approach of taking a log2 transformation, but
      has not been validated on a spike-in experiment. We apply VST to the data from a
      recently published spike-in experiment and compare it both to a regular log2
      analysis and a recently recommended analysis that can be applied if all raw data
      are available. FINDINGS: VST provides more power to detect differentially
      expressed genes than a log2 transformation. However, the gain in power is roughly
      the same as utilizing the raw data from an experiment and weighting observations
      accordingly. VST is still advantageous when large changes in expression are
      anticipated, while a weighted log2 approach performs better for smaller changes.
      CONCLUSION: VST can be recommended for summarized Illumina data regardless of
      which Illumina pre-processing options have been used. However, using the raw data
      is still encouraged whenever possible.

PMID- 18710544
TI  - Effective therapeutic dosage of antipsychotic medications in patients with
      psychotic symptoms: Is there a racial difference?
AB  - BACKGROUND: Genetic make up had been known to influence pharmacokinetics and
      pharmacodynamics of psychotropic medications. Time separation in evolutionary
      trend in Africans, Orientals and Caucasians had been thought a possible
      explanation for the observed racial variation in activities of Cytochrome P 450
      (CYP 450) enzymes, which are responsible for metabolism of psychotropic and other
      medications in human. Past studies on pharmacokinetics and pharmacodynamics of
      antipsychotic medications and socio-cultural factors influencing response to
      antipsychotic medications had consistently giving an inkling of possible racial
      difference in symptoms response to antipsychotic medications. Another growing
      body of evidence subscribing to possible racial difference in psychotic symptoms
      response to antipsychotic medications is the observed variation in antipsychotic
      medications prescription pattern and dosage across races and regions. Empirical
      observation had shown that dosage prescription pattern of antipsychotic
      medications in most Sub-Saharan African countries deviates from the standard
      prescription guidelines published for use in western parts of the world. Studies
      coming from the United States (U.S) had consistently reported a higher dosage of
      antipsychotic medications prescription for African-American patients compared to
      their Caucasian counterparts. Research on East Asia Psychotropic Prescription
      (REAP) study had also identified high dosage antipsychotic medications
      prescription pattern well above the recommended dose of 1,000 mg Chlorpromazine
      equivalent per day as common practices in some East Asian countries. PRESENTATION
      OF THE HYPOTHESIS: The pertinent question is why the apparent differences in
      dosage prescription practices across races and regions? The possibility of racial
      differences in psychotic symptoms response to antipsychotic medications rather
      than clinicians' prescription attitudes was entertained. TESTING THE HYPOTHESIS:
      Future carefully controlled studies might be needed to test the proposed
      hypothesis of racial differences in psychotic symptoms response to antipsychotic
      medications. IMPLICATION OF THE HYPOTHESIS: There might be actual racial
      influence on psychotic symptoms response to antipsychotic medications. If future
      carefully controlled studies uphold the hypothesis of racial differences in
      psychotic symptoms response to antipsychotic medications, there might be need to
      draw up new treatment or prescription guidelines that would put into
      consideration variations in genetic make up and consequent racial differences in
      psychotic symptoms response to antipsychotic medications.

PMID- 18710545
TI  - Lactogenic differentiation of HC11 cells is not accompanied by downregulation of
      AP-2 transcription factor genes.
AB  - BACKGROUND: During pregnancy the mammary epithelium undergoes a complex
      developmental process which culminates in the generation of the milk-secreting
      epithelium. Secretory epithelial cells display lactogenic differentiation which
      is characterized by the expression of milk protein genes, such as beta-casein or
      whey acidic protein (WAP). Transcription factors AP-2alpha and AP-2gamma are
      downregulated during lactation, and their overexpression in transgenic mice
      impaired the secretory differentiation of the mammary epithelium, resulting in
      lactation failure. To explore whether the downregulation of AP-2alpha and AP
      2gamma is of functional significance for lactogenic differentiation, we analyzed
      the expression of the AP-2 family members during the lactogenic differentiation
      of HC11 mammary epithelial cells in vitro. Differentiation of HC11 cells was
      induced following established protocols by applying the lactogenic hormones
      prolactin, dexamethasone and insulin. FINDINGS: HC11 cells express all AP-2
      family members except AP-2delta. Using RT-PCR we could not detect a
      downregulation of any of these genes during the lactogenic differentiation of
      HC11 cells in vitro. This finding was confirmed for AP-2alpha and AP-2gamma using
      Northern analysis. Differentiating HC11 cells displayed lower expression levels
      of milk protein genes than mammary glands of mid-pregnant or lactating mice.
      CONCLUSION: The extent of lactogenic differentiation of HC11 cells in vitro is
      limited compared to mammary epithelium undergoing secretory differentiation in
      vivo. Downregulation of AP-2 transcription factor genes is not required for
      lactogenic differentiation of HC11 cells but may functionally be involved in
      aspects of lactogenic differentiation in vivo that are not reflected by the HC11
      system.

PMID- 18710546
TI  - Discovering and verifying DNA polymorphisms in a mung bean [V. radiata (L.) R.
      Wilczek] collection by EcoTILLING and sequencing.
AB  - BACKGROUND: Vigna radiata, which is classified in the family Fabaceae, is an
      important economic crop and a dietary staple in many developing countries. The
      species radiata can be further subdivided into varieties of which the variety
      sublobata is currently acknowledged as the putative progenitor of radiata.
      EcoTILLING was employed to identify single nucleotide polymorphisms (SNPs) and
      small insertions/deletions (INDELS) in a collection of Vigna radiata accessions.
      FINDINGS: A total of 157 DNA polymorphisms in the collection were produced from
      ten primer sets when using V. radiata var. sublobata as the reference. The
      majority of polymorphisms detected were found in putative introns. The banding
      patterns varied from simple to complex as the number of DNA polymorphisms between
      two pooled samples increased. Numerous SNPs and INDELS ranging from 4-24 and 1-6,
      respectively, were detected in all fragments when pooling V. radiata var.
      sublobata with V. radiata var. radiata. On the other hand, when accessions of V.
      radiata var. radiata were mixed together and digested with CEL I relatively few
      SNPs and no INDELS were detected. CONCLUSION: EcoTILLING was utilized to identify
      polymorphisms in a collection of mung bean, which previously showed limited
      molecular genetic diversity and limited morphological diversity in the flowers
      and pod descriptors. Overall, EcoTILLING proved to be a powerful genetic analysis
      tool providing the rapid identification of naturally occurring variation.

PMID- 18710547
TI  - Limitations in assessing nerve growth factor levels in aqueous humor samples from
      human eyes.
AB  - BACKGROUND: Nerve growth factor (NGF) helps in the healing and survival of
      ganglion cells, photoreceptors, and optic nerve after injury and has been
      implicated to have a role in pathophysiology of glaucoma. So far, in animal
      studies, injury to iris in vitro has revealed an increase in NGF levels in
      aqueous. There is a great interest in investigating the levels of NGF in human
      aqueous in glaucomatous eyes, as suggested by animal studies, to gain a better
      understanding of the pathophysiology of glaucoma. FINDINGS: In this study, we
      examined the presence of NGF levels in aqueous humor collected from human eyes
      and the limitations in determining the NGF levels in human samples. NGF was
      assessed by ELISA immunoassay in undiluted aqueous samples collected from 32
      consecutive patients undergoing surgery for cataract (control) or primary open
      angle glaucoma (POAG). Recombinant NGF was used as positive control. NGF levels
      were below undetectable levels in aqueous humor from eyes with POAG and controls
      by immunoassay. Less than 10% of samples had detectable NGF levels and these were
      considered outliers. CONCLUSION: Our result highlights the undetectable levels of
      NGF in human aqueous samples.

PMID- 18710548
TI  - Drugs, alcohol and sexual health: opportunities to influence risk behaviour.
AB  - BACKGROUND: Alcohol and drug consumption can affect judgment and may contribute
      towards an increased likelihood of engaging in risky sexual behaviour. In this
      cross sectional survey of clients attending STI services levels of drug and
      alcohol use were assessed using two standardised drug and alcohol screening
      instruments (the PAT and the SDS). FINDINGS: The rates of hazardous alcohol
      consumption were similar to those found among patients attending A&E departments.
      Approximately 15% of clients indicated possible dependence on alcohol or other
      drugs, and these clients were likely to cite their substance use as related to
      their attendance, and to accept the offer of help or advice. CONCLUSION: The use
      of brief screening instruments as part of routine clinical practice is
      recommended. The STI clinic is well placed to identify substance use and to offer
      advice and/or onward referral to specialist services.

PMID- 18710549
TI  - Drift by drift: effective population size is limited by advection.
AB  - BACKGROUND: Genetic estimates of effective population size often generate
      surprising results, including dramatically low ratios of effective population
      size to census size. This is particularly true for many marine species, and this
      effect has been associated with hypotheses of "sweepstakes" reproduction and
      selective hitchhiking. RESULTS: Here we show that in advective environments such
      as oceans and rivers, the mean asymmetric transport of passively dispersed
      reproductive propagules will act to limit the effective population size in
      species with a drifting developmental stage. As advection increases, effective
      population size becomes decoupled from census size as the persistence of novel
      genetic lineages is restricted to those that arise in a small upstream portion of
      the species domain. CONCLUSION: This result leads to predictions about the
      maintenance of diversity in advective systems, and complements the "sweepstakes"
      hypothesis and other hypotheses proposed to explain cases of low allelic
      diversity in species with high fecundity. We describe the spatial extent of the
      species domain in which novel allelic diversity will be retained, thus
      determining how large an appropriately placed marine reserve must be to allow the
      persistence of endemic allelic diversity.

PMID- 18710551
TI  - Carbon monoxide poisoning in a patient with carbon dioxide retention: a
      therapeutic challenge.
AB  - We present the case of a 70 year-old man with carbon monoxide poisoning
      following a house fire. A significant smoking history and likely underlying
      chronic lung pathology complicated treatment, as due to symptomatic retention of
      carbon dioxide we were unable to use high-flow oxygen to facilitate the
      elimination of carbon monoxide. We suggest that patients with risk factors for
      obstructive lung disease be monitored extremely carefully during treatment for
      carbon monoxide toxicity.

PMID- 18710550
TI  - Interlobular and intralobular mammary stroma: genotype may not reflect phenotype.
AB  - BACKGROUND: The normal growth and function of mammary epithelial cells depend on
      interactions with the supportive stroma. Alterations in this communication can
      lead to the progression or expansion of malignant growth. The human mammary gland
      contains two distinctive types of fibroblasts within the stroma. The epithelial
      cells are surrounded by loosely connected intralobular fibroblasts, which are
      subsequently surrounded by the more compacted interlobular fibroblasts. The
      different proximity of these fibroblasts to the epithelial cells suggests
      distinctive functions for these two subtypes. In this report, we compared the
      gene expression profiles between the two stromal subtypes. METHODS: Fresh normal
      breast tissue was collected from reduction mammoplasty patients and immediately
      placed into embedding medium and frozen on dry ice. Tissue sections were
      subjected to laser capture microscopy to isolate the interlobular from the
      intralobular fibroblasts. RNA was prepared and subjected to microarray analysis
      using the Affymetrix Human Genome U133 GeneChip. Data was analyzed using the Affy
      and Limma packages available from Bioconductor. Findings from the microarray
      analysis were validated by RT-PCR and immunohistochemistry. RESULTS: No
      statistically significant difference was detected between the gene expression
      profiles of the interlobular and intralobular fibroblasts by microarray analysis
      and RT-PCR. However, for some of the genes tested, the protein expression
      patterns between the two subtypes of fibroblasts were significantly different.
      CONCLUSION: This study is the first to report the gene expression profiles of the
      two distinct fibroblast populations within the human mammary gland. While there
      was no significant difference in the gene expression profiles between the groups,
      there was an obvious difference in the expression pattern of several proteins
      tested. This report also highlights the importance of studying gene regulation at
      both the transcriptional and post-translational level.

PMID- 18710552
TI  - An additional muscle belly of the first lumbrical muscle.
AB  - INTRODUCTION: Lumbrical muscles play a vital role in the precision movements of
      the hand, along with the thenar, hypothenar and interossei muscles. The variation
      in the lumbrical muscle is clinically significant. CASE PRESENTATION: During
      routine dissection of an adult male cadaver, we observed an additional muscle
      belly of the first lumbrical muscle took origin from the tendon of the flexor
      digitorum superficialis (FDS) to the index finger, close to the proximal margin
      of the flexor retinaculum. CONCLUSION: The presence of such an additional muscle
      in the carpal tunnel should be considered in the aetiology of carpal tunnel
      syndrome (CTS).

PMID- 18710553
TI  - Male sexual ornament size is positively associated with reproductive morphology
      and enhanced fertility in the stalk-eyed fly Teleopsis dalmanni.
AB  - BACKGROUND: Exaggerated male ornaments and displays often evolve in species where
      males only provide females with ejaculates during reproduction. Although "good
      genes" arguments are typically invoked to explain this phenomenon, a simpler
      alternative is possible if variation in male reproductive quality (e.g. sperm
      number, ejaculate content, mating rate) is an important determinant of female
      reproductive success. The "phenotype-linked fertility hypothesis" states that
      female preference for male ornaments or displays has been selected to ensure
      higher levels of fertility and has driven the evolution of exaggerated male
      traits. Females of the stalk-eyed fly Teleopsis dalmanni must mate frequently to
      maintain high levels of fertility and prefer to mate with males exhibiting large
      eyespan, a condition-dependent sexual ornament. If eyespan indicates male
      reproductive quality, females could directly increase their reproductive success
      by mating with males with large eyespan. Here we investigate whether male eyespan
      indicates accessory gland and testis length, and then ask whether mating with
      large eyespan males affects female fertility. RESULTS: Male eyespan was a better
      predictor of two key male reproductive traits--accessory gland and testis length-
      than was body size alone. This positive relationship held true over three levels
      of increasing environmental stress during the maturation of the adult accessory
      glands and testes. Furthermore, females housed with a large eyespan male
      exhibited higher levels of fertility than those with small eyespan males.
      CONCLUSION: Male eyespan in stalk-eyed flies is subject to strong directional
      mate preference and is a reliable indicator of male reproductive quality--both
      because males with larger eyespan have bigger accessory glands and testes, and
      also as they confer higher fertility on females. Fertility enhancement may have
      arisen because males with larger eyespan mated more often and/or because they
      transferred more sperm or other substances per ejaculate. The need to ensure high
      levels of fertility could thus have been an important selective force in the
      coevolution of female preference and male eyespan in stalk-eyed flies. Our
      results support the phenotype-linked fertility hypothesis and suggest that it
      might be of general importance in explaining the evolution of exaggerated male
      ornaments and displays in species where males only provide females with
      ejaculates during reproduction.

PMID- 18710554
TI  - Neurocysticercosis as a first presentation of tonic-clonic seizures: a case
      report.
AB  - We report the case of a 28 year-old immigrant Asian man from the Punjab region
      with a first presentation of seizures. This patient had no significant past
      medical history, but suffered several headaches in the preceding week and was
      pyrexial on presentation. A CT scan of his head showed a single area of
      subcortical low attenuation initially suggesting ischaemia. A lumbar puncture and
      CSF examination was unremarkable. Further investigation revealed discrete
      calcified gluteal lesions on pelvic X-ray, and serum immunology positive for
      cysticercosis. The diagnosis of neurocysticercosis was made, and the patient
      improved on dexamethasone and a short course of vermicide, to be discharged a
      week later. With increasing global migration, the prevalence of neurological
      parasitic infections seen in the UK is likely to rise. This case highlights the
      importance of careful interpretation of non-specific head CTs in the context of
      first presentation of seizures in a susceptible population.

PMID- 18710555
TI  - A case of demand ischemia from phendimetrazine.
AB  - INTRODUCTION: Phendimetrazine is a medication currently being used to help
      patients with weight loss. It shares a chemical structure with amphetamines. As
      such, it shares some of the same toxicities, which can include cardiac toxicity.
      This case highlights this principle. CASE PRESENTATION: a 54 year old Caucasian
      female presented to our urgent care facility with complaints of chest pains and
      other symptoms suggestive of acute coronary syndrome. Ultimately, she was
      transferred to the emergency room. After evaluation there, it appeared she was
      having demand ischemia from prescription diet pills CONCLUSION: This case report
      demonstrates the potential dangers of amphetamine based diet pills. There have
      been other cases of cardiomyopathies related to phendimetrazine, but it is
      something that is rarely recognized in an outpatient setting. A case such as this
      demonstrates the importance of obtaining a careful medication history in all
      patients and in recognizing diet pills with an amphetamine base can cause cardiac
      toxicity.

PMID- 18710556
TI  - Giant cell tumour in the diaphysis of radius - a report.
AB  - BACKGROUND: We present a case of a 35 yrs old female who presented with swelling
      over her forearm. This is a rare case of a giant cell tumour in a nonepiphyseal
      region. METHODS: Case report and presentation of clinical, radiological and
      histological data on single case of giant cell tumour of diaphysis of radius.
      RESULTS: Although age, clinical features and radiological features are helpful,
      it is still the histology that helps to clinch the diagnosis. CONCLUSION: A
      thorough literature search and an exhaustive online search using various search
      engines revealed seven reported cases of giant cell tumours in the diaphysis of
      long bones. We reiterate the fact that irrespective of the location, a giant cell
      tumour should be diagnosed based on its histology.

PMID- 18710557
TI  - Brugada syndrome during physical therapy: a case report.
AB  - This case report describes about a young, male patient with persisting syncope
      during physical therapy for complex regional pain syndrome type 1 after
      metatarsal fractures.The patient was referred to the Emergency Department, where
      Brugada syndrome was diagnosed. A cardioverter defibrillator was prophylactically
      implanted successfully. After this procedure, there were no contraindications for
      resuming further physical therapy for his painful foot. No clear causal inference
      with Brugada could be drawn from the complex regional pain syndrome type 1 or
      physical therapy described in this case report. Hyperthermia may, however, occur
      during such therapy, which is associated with dysrhythmia in general.

PMID- 18710558
TI  - Neonatal group A streptococcal meningitis: a case report and review of the
      literature.
AB  - INTRODUCTION: Group A streptococcus is a rare cause of neonatal meningitis. A
      review of MEDLINE database since1966 revealed only 15 documented cases of group A
      streptococcal meningitis in neonates. CASE REPORT: A previously healthy 28 days
      old male neonate presented with a history of irritability, fever, and focal
      seizures. Cerebrospinal fluid analysis and culture confirmed the diagnosis of
      group A streptococcal meningitis. The clinical course was complicated by the
      development of brain abscess. The patient made full recovery following a surgical
      drainage of the abscess and a 6-week total course of antibiotics. CONCLUSION:
      Although it is an uncommon organism, clinician should always consider group A
      streptococcal infection and its potential complications in the differential
      diagnosis and management of neonatal meningitis.

PMID- 18710559
TI  - Dry season ecology of Anopheles gambiae complex mosquitoes in The Gambia.
AB  - BACKGROUND: Malaria in The Gambia is highly seasonal, with transmission occurring
      as Anopheles gambiae s.l. populations expand during and immediately after a
      single annual rainy season that lasts from June to October. There has been very
      limited investigation of the ecology of vectors during the dry season, when
      numbers are very limited and distributions may be restricted. METHODS: Weekly
      adult mosquito collections (pyrethrum spray, light trap, and search collections
      from rooms, as well as light trap collections from animal shelters, abandoned
      wells and grain stores), and artificial sentinel breeding site surveys were
      performed in four villages near the upper tidal and partially saline part of the
      Gambia River in the last four months of an annual dry season (March to June).
      Mosquito species were identified by morphological and DNA analysis, and ELISA
      assays were performed to test for Plasmodium falciparum sporozoites and human
      blood meal components. RESULTS: Adults of An. gambiae s.l. were collected
      throughout the period, numbers increasing towards the end of the dry season when
      humidity was increasing. Adult collections were dominated by An. melas (86%),
      with An. gambiae s.s. (10%) and An. arabiensis (3%) also present throughout. Most
      females collected in room search and spray collections contained blood meals, but
      most from light traps were unfed. None of the females tested (n = 1709) contained
      sporozoites. Larvae (mostly An. gambiae s.s.) were recovered from artificial
      sentinel breeding sites in the two villages that had freshwater pools. These two
      villages had the highest proportions of An. gambiae s.s. adults, and experienced
      the most substantial increase in proportions of An. gambiae s.s. after the onset
      of rains. CONCLUSION: During the dry season population minimum, An. melas was the
      predominant vector species, but differences among villages in availability of
      fresh-water breeding sites correlate with egg laying activity and relative
      numbers of An. gambiae s.s. adults, and with the increase in this species
      immediately after the beginning of the rains. Local variation in dry season
      vector persistence is thus likely to influence spatial heterogeneity of
      transmission intensity in the early part of the rainy season.

PMID- 18710560
TI  - Femoral-tibial-synostosis in a child with Roberts syndrome (Pseudothalidomide): a
      case report.
AB  - BACKGROUND: Roberts syndrome (Pseudothalidomide) is a rare birth defect that
      causes severe bone malformation complex. The bones of the arms, and in some cases
      other appendages, may be extremely shortened and even absent. The fingers of the
      hands may be fused. An extreme case results in the absence of the upper bones of
      both the arms and legs so that the hands and feet appear attached directly to the
      body. This is called tetraphocomelia. CASE PRESENTATION: We report on a two-year
      old boy of Austrian origin who manifests a constellation of malformation complex
      include prenatal and postnatal growth retardation, craniofacial anomalies and
      defective development of all four extremities. The overall clinico-radiographic
      features were compatible with Roberts syndrome (Pseudothalidomide). Significant
      unilateral femoral-tibial synostosis was additional malformation. CONCLUSION:
      Associated malformations and symptoms may be the key factor in the differential
      diagnosis of neonatal malformation complex. Roberts's syndrome may be genetically
      transmitted within families as an autosomal recessive trait or may be the result
      of spontaneous/sporadic changes in the gene. Because the signs of the disorder so
      closely mimic those caused by the ingestion of thalidomide, the term "pseudo
      thalidomide" is frequently used.In this report we describe total femorotibial
      fusion in a child manifesting the phenotypic features consistent with Roberts
      syndrome from a healthy parents but first cousins in Austria. Aggressive medical
      intervention is of prime importance, as is forthright parental counselling when
      discussing the possible outcome for these patients.

PMID- 18710561
TI  - Global transcriptome analysis reveals circadian regulation of key pathways in
      plant growth and development.
AB  - BACKGROUND: As nonmotile organisms, plants must rapidly adapt to ever-changing
      environmental conditions, including those caused by daily light/dark cycles. One
      important mechanism for anticipating and preparing for such predictable changes
      is the circadian clock. Nearly all organisms have circadian oscillators that,
      when they are in phase with the Earth's rotation, provide a competitive
      advantage. In order to understand how circadian clocks benefit plants, it is
      necessary to identify the pathways and processes that are clock controlled.
      RESULTS: We have integrated information from multiple circadian microarray
      experiments performed on Arabidopsis thaliana in order to better estimate the
      fraction of the plant transcriptome that is circadian regulated. Analyzing the
      promoters of clock-controlled genes, we identified circadian clock regulatory
      elements correlated with phase-specific transcript accumulation. We have also
      identified several physiological pathways enriched for clock-regulated changes in
      transcript abundance, suggesting they may be modulated by the circadian clock.
      CONCLUSION: Our analysis suggests that transcript abundance of roughly one-third
      of expressed A. thaliana genes is circadian regulated. We found four promoter
      elements, enriched in the promoters of genes with four discrete phases, which may
      contribute to the time-of-day specific changes in the transcript abundance of
      these genes. Clock-regulated genes are over-represented among all of the
      classical plant hormone and multiple stress response pathways, suggesting that
      all of these pathways are influenced by the circadian clock. Further exploration
      of the links between the clock and these pathways will lead to a better
      understanding of how the circadian clock affects plant growth and leads to
      improved fitness.

PMID- 18710562
TI  - Phagocytosis of haemozoin (malarial pigment) enhances metalloproteinase-9
      activity in human adherent monocytes: role of IL-1beta and 15-HETE.
AB  - BACKGROUND: It has been shown previously that human monocytes fed with haemozoin
      (HZ) or trophozoite-parasitized RBCs displayed increased matrix metalloproteinase
      9 (MMP-9) enzyme activity and protein/mRNA expression and increased TNF
      production, and showed higher matrix invasion ability. The present study utilized
      the same experimental model to analyse the effect of phagocytosis of: HZ,
      delipidized HZ, beta-haematin (lipid-free synthetic HZ) and trophozoites on
      production of IL-1beta and MMP-9 activity and expression. The second aim was to
      find out which component of HZ was responsible for the effects. METHODS: Native
      HZ freshly isolated from Plasmodium falciparum (Palo Alto strain, Mycoplasma
      free), delipidized HZ, beta-haematin (lipid-free synthetic HZ), trophozoites and
      control meals such as opsonized non-parasitized RBCs and inert latex particles,
      were fed to human monocytes. The production of IL-1beta by differently fed
      monocytes, in presence or absence of specific MMP-9 inhibitor or anti-hIL-1beta
      antibodies, was quantified in supernatants by ELISA. Expression of IL-1beta was
      analysed by quantitative real-time RT-PCR. MMP-9 activity and protein expression
      were quantified by gelatin zymography and Western blotting. RESULTS: Monocytes
      fed with HZ or trophozoite-parasitized RBCs generated increased amounts of IL
      1beta and enhanced enzyme activity (in cell supernatants) and protein/mRNA
      expression (in cell lysates) of monocyte MMP-9. The latter appears to be causally
      related to enhanced IL-1beta production, as enhancement of both expression and
      enzyme activity were abrogated by anti-hIL-1beta Abs. Upregulation of IL-1beta
      and MMP-9 were absent in monocytes fed with beta-haematin or delipidized HZ,
      indicating a role for HZ-attached or HZ-generated lipid components. 15-HETE
      (15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid) a potent lipoperoxidation
      derivative generated by HZ from arachidonic acid via haem-catalysis was
      identified as one mediator possibly responsible for increase of both IL-1beta
      production and MMP-9 activity. CONCLUSION: Results indicate that specific
      lipoperoxide derivatives generated by HZ may play a role in modulating production
      of IL-1beta and MMP-9 expression and activity in HZ/trophozoite-fed human
      monocytes. Results may clarify aspects of cerebral malaria pathogenesis, since
      MMP-9, a metalloproteinase able to disrupt the basal lamina is possibly involved
      in generation of hallmarks of cerebral malaria, such as blood-brain barrier
      endothelium dysfunction, localized haemorrhages and extravasation of phagocytic
      cells and parasitized RBCs into brain tissues.

PMID- 18710563
TI  - A human genome-wide library of local phylogeny predictions for whole-genome
      inference problems.
AB  - BACKGROUND: Many common inference problems in computational genetics depend on
      inferring aspects of the evolutionary history of a data set given a set of
      observed modern sequences. Detailed predictions of the full phylogenies are
      therefore of value in improving our ability to make further inferences about
      population history and sources of genetic variation. Making phylogenetic
      predictions on the scale needed for whole-genome analysis is, however, extremely
      computationally demanding. RESULTS: In order to facilitate phylogeny-based
      predictions on a genomic scale, we develop a library of maximum parsimony
      phylogenies within local regions spanning all autosomal human chromosomes based
      on Haplotype Map variation data. We demonstrate the utility of this library for
      population genetic inferences by examining a tree statistic we call
      'imperfection,' which measures the reuse of variant sites within a phylogeny.
      This statistic is significantly predictive of recombination rate, shows
      additional regional and population-specific conservation, and allows us to
      identify outlier genes likely to have experienced unusual amounts of variation in
      recent human history. CONCLUSION: Recent theoretical advances in algorithms for
      phylogenetic tree reconstruction have made it possible to perform large-scale
      inferences of local maximum parsimony phylogenies from single nucleotide
      polymorphism (SNP) data. As results from the imperfection statistic demonstrate,
      phylogeny predictions encode substantial information useful for detecting genomic
      features and population history. This data set should serve as a platform for
      many kinds of inferences one may wish to make about human population history and
      genetic variation.

PMID- 18710564
TI  - Severe hepatitis with autoimmune features following a HHV-6: a case report.
AB  - HHV-6 has been identified as the aetiologic agent of exanthem subitum in infants
      and an acute febrile illness in young children. HHV-6 probably remains latent in
      the body after the primary infection and it reactivates upon host
      immunosuppression in a manner similar to other human herpes viruses. Primary HHV
      6 infection in adults is very rare and it is not clear whether disease
      manifestations are similar to those observed in children.We report the case of
      acute hepatitis in a 18-year-old immunocompetent woman presenting with sever
      jaundice and liver dysfunction. Serum immunoglobulin levels were elevated (3.8
      gr/dl) with a titre of anti nucleus antibody of 1:640. Serological data
      demonstrated the presence of IgM antibodies against human herpesvirus-6 in the
      serum and of viral DNA on liver biopsy by real time quantitative polymerase chain
      reaction, with a viral load of 280 genomes/106 of cellular genomes. No other
      etiologic agents were found to induce hepatitis and the patient was diagnosed as
      having HHV-6 triggered autoimmune acute hepatitis.

PMID- 18710565
TI  - An enhanced partial order curve comparison algorithm and its application to
      analyzing protein folding trajectories.
AB  - BACKGROUND: Understanding how proteins fold is essential to our quest in
      discovering how life works at the molecular level. Current computation power
      enables researchers to produce a huge amount of folding simulation data. Hence
      there is a pressing need to be able to interpret and identify novel folding
      features from them. RESULTS: In this paper, we model each folding trajectory as a
      multi-dimensional curve. We then develop an effective multiple curve comparison
      (MCC) algorithm, called the enhanced partial order (EPO) algorithm, to extract
      features from a set of diverse folding trajectories, including both successful
      and unsuccessful simulation runs. The EPO algorithm addresses several new
      challenges presented by comparing high dimensional curves coming from folding
      trajectories. A detailed case study on miniprotein Trp-cage 1 demonstrates that
      our algorithm can detect similarities at rather low level, and extract
      biologically meaningful folding events. CONCLUSION: The EPO algorithm is general
      and applicable to a wide range of applications. We demonstrate its generality and
      effectiveness by applying it to aligning multiple protein structures with low
      similarities. For user's convenience, we provide a web server for the algorithm
      at http://db.cse.ohio-state.edu/EPO.

PMID- 18710566
TI  - An elderly woman with 'Red Man Syndrome' in association with oral vancomycin
      therapy: a case report.
AB  - INTRODUCTION: 'Red Man Syndrome' is a recognized adverse reaction to intravenous
      vancomycin therapy. This case concerns an elderly woman who developed a 'Red Man
      Syndrome' reaction whilst on oral vancomycin therapy for Clostridium difficile (C
      difficile) diarrhoea. Isolated case reports exist recording this reaction in
      association with oral vancomycin therapy in patients with inflammatory bowel
      conditions or impaired renal function, of which this patient had both. CASE
      PRESENTATION: An 82 year old Caucasian woman who developed C. difficile diarrhoea
      after co-amoxiclav therapy for a urinary tract infection. She was treated with
      oral vancomycin therapy during which she developed a widespread erythematous rash
      in keeping with that of 'Red Man Syndrome'. This rash resolved on stopping the
      oral vancomycin. CONCLUSION: This case is important in the light of the
      increasing use of oral vancomycin to treat C. difficile diarrhoea, a rising
      problem in the UK. It also calls us to review our understanding of the mechanism
      of the 'Red Man Syndrome' reaction. It is possible that significant absorption of
      orally administered vancomycin occurs in the presence of an inflammatory bowel
      condition.

PMID- 18710567
TI  - TH-17 cells in rheumatoid arthritis.
AB  - INTRODUCTION: The aim of this study was to quantify the number of T-helper (TH)
      17 cells present in rheumatoid arthritis (RA) synovial fluid (SF) and to
      determine the level of interleukin (IL)-17 cytokine in RA, osteoarthritis (OA)
      and normal synovial tissue, as well as to examine SF macrophages for the presence
      of IL-23, IL-27 and interferon (IFN)-gamma. METHODS: Peripheral blood (PB)
      mononuclear cells from normal and RA donors and mononuclear cells from RA SF were
      examined either without stimulation or after pretreatment with IL-23 followed by
      stimulation with phorbol myristate acetate (PMA) plus ionomycin (P/I). The
      abundance of TH-17 cells in RA SF was determined by flow cytometry. IL-17 levels
      were quantified in synovial tissue from RA, OA and normal individuals by ELISA
      and IL-23 was identified in SFs by ELISA. RA SF and control in vitro
      differentiated macrophages were either untreated or treated with the toll-like
      receptor (TLR) 2 ligand peptidoglycan, and then IL-23, IL-27 and IFN-gamma mRNA
      levels were quantified by real-time polymerase chain reaction (RT-PCR). RESULTS:
      Treatment with P/I alone or combined with IL-23 significantly increased the
      number of TH-17 cells in normal, RA PB and RA SF. With or without P/I plus IL-23,
      the percentage of TH-17 cells was higher in RA SF compared with normal and RA PB.
      IL-17 levels were comparable in OA and normal synovial tissues, and these values
      were significantly increased in RA synovial tissue. Although IL-17 was readily
      detected in RA SFs, IL-23 was rarely identified in RA SF. However, IL-23 mRNA was
      significantly increased in RA SF macrophages compared with control macrophages,
      with or without TLR2 ligation. IL-27 mRNA was also significantly higher in RA SF
      compared with control macrophages, but there was no difference in IL-27 levels
      between RA and control macrophages after TLR2 ligation. IFN-gamma mRNA was also
      detectable in RA SF macrophages but not control macrophages and the increase of
      IFN-gamma mRNA following TLR2 ligation was greater in RA SF macrophages compared
      with control macrophages. CONCLUSION: These observations support a role for TH-17
      cells in RA. Our observations do not strongly support a role for IL-23 in the
      generation of TH-17 cells in the RA joint, however, they suggest strategies that
      enhance IL-27 or IFN-gamma might modulate the presence of TH-17 cells in RA.

PMID- 18710568
TI  - Genome sequence of the Bacteroides fragilis phage ATCC 51477-B1.
AB  - The genome of a fecal pollution indicator phage, Bacteroides fragilis ATCC 51477
      B1, was sequenced and consisted of 44,929 bases with a G+C content of 38.7%.
      Forty-six putative open reading frames were identified and genes were organized
      into functional clusters for host specificity, lysis, replication and regulation,
      and packaging and structural proteins.

PMID- 18710569
TI  - VisualRepbase: an interface for the study of occurrences of transposable element
      families.
AB  - BACKGROUND: Repbase is a reference database of eukaryotic repetitive DNA, which
      includes prototypic sequences of repeats and basic information described in
      annotations. Repbase already has software for entering new sequence families and
      for comparing the user's sequence with the database of consensus sequences.
      RESULTS: We describe the software named VisualRepbase and the associated
      database, which allow for displaying and analyzing all occurrences of
      transposable element families present in an annotated genome. VisualRepbase is a
      Java-based interface which can download selected occurrences of transposable
      elements, show the distribution of given families on the chromosome, and present
      the localization of these occurrences with regard to gene annotations and other
      families of transposable elements in Repbase. In addition, it has several
      features for saving the graphical representation of occurrences, saving all
      sequences in FASTA format, and searching and saving all annotated genes that are
      surrounded by these occurrences. CONCLUSION: VisualRepbase is available as a
      downloadable version. It can be found at http://girinst.org/repbase/update/visual
      repbase.html.

PMID- 18710570
TI  - Work-related musculoskeletal disorders among Nigerian physiotherapists.
AB  - BACKGROUND: Physiotherapists are known to be prone to Work- related
      musculoskeletal disorders (WRMDs) but its prevalence among physiotherapists in
      Nigeria has not been reported. This study investigated the prevalence and work
      factors of WRMDs among physiotherapists in Nigeria. METHODS: A cross- sectional
      survey was administered to physiotherapists in different parts of Nigeria using a
      2- part questionnaire with items adopted from questionnaires used for similar
      studies around the world. Two hundred and seventeen copies of the questionnaire
      were distributed for self administration but 126 physiotherapists returned
      completed surveys for a 58.1% response. The data were analyzed using SPPS version
      10 at alpha level of 0.05. Descriptive statistics of frequency and percentages
      and inferential statistics of chi2 were used as appropriate for data analysis.
      RESULTS: Reported 12- month prevalence of WRMDs among Nigerian physiotherapists
      was 91.3%. Prevalence of WRMDs was significantly higher in female
      physiotherapists (p = 0.007) and those with lower body mass index (p = 0.045).
      The low back (69.8%) was the most commonly affected body part, followed by the
      neck (34.1%). Fifty percent of the physiotherapists first experienced their WRMDs
      within five years of graduation and the highest prevalence (61.7%) was found
      among physiotherapists younger than 30 years. Treating large number of patients
      in a day was cited by most (83.5%) of the respondents as the most important work
      factor for their WRMDs. The most commonly adopted coping strategy identified was
      for the therapists to modify their position and/or the patient's position
      (64.3%). Majority of the respondents (87.0%) did not leave the profession but
      62.6% changed and/or modified their treatment because of their WRMDs. CONCLUSION:
      The prevalence of WRMDs among physiotherapists in Nigeria is higher than most
      values reported for their counterparts around the world. The coping strategies
      and work factors of WRMDs among Nigerian physiotherapists are mostly similar to
      those of their counterparts elsewhere.

PMID- 18710571
TI  - Tobacco use induces anti-apoptotic, proliferative patterns of gene expression in
      circulating leukocytes of Caucasian males.
AB  - BACKGROUND: Strong epidemiologic evidence correlates tobacco use with a variety
      of serious adverse health effects, but the biological mechanisms that produce
      these effects remain elusive. RESULTS: We analyzed gene transcription data to
      identify expression spectra related to tobacco use in circulating leukocytes of
      67 Caucasian male subjects. Levels of cotinine, a nicotine metabolite, were used
      as a surrogate marker for tobacco exposure. Significance Analysis of Microarray
      and Gene Set Analysis identified 109 genes in 16 gene sets whose transcription
      levels were differentially regulated by nicotine exposure. We subsequently
      analyzed this gene set by hyperclustering, a technique that allows the data to be
      clustered by both expression ratio and gene annotation (e.g. Gene Ontologies).
      CONCLUSION: Our results demonstrate that tobacco use affects transcription of
      groups of genes that are involved in proliferation and apoptosis in circulating
      leukocytes. These transcriptional effects include a repertoire of transcriptional
      changes likely to increase the incidence of neoplasia through an altered
      expression of genes associated with transcription and signaling, interferon
      responses and repression of apoptotic pathways.

PMID- 18710572
TI  - Circulating immune complexes contain citrullinated fibrinogen in rheumatoid
      arthritis.
AB  - INTRODUCTION: There is increasing evidence that autoantibodies and immune
      complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the
      autoantigens incorporated in ICs in RA remain incompletely characterised.
      METHODS: We used the C1q protein to capture ICs from plasma derived from human RA
      and control patients. Antibodies specific for immunoglobulin were used to detect
      ICs, and fibrinogen antibodies were used to detect fibrinogen-containing ICs. RA
      and control plasma were separated by liquid chromatography, and fractions then
      characterised by ELISA, immunoblotting and mass spectrometry. Immunohistochemical
      staining was performed on rheumatoid synovial tissue. RESULTS: C1q-immunoassays
      demonstrated increased levels of IgG (p = 0.01) and IgM (p = 0.0002) ICs in
      plasma derived from RA patients possessing anti-cyclic citrullinated peptide
      (CCP+) autoantibodies as compared with healthy controls. About one-half of the
      anti-CCP+ RA possessed circulating ICs containing fibrinogen (p = 0.0004).
      Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high
      molecular weight fractions that contained ICs. Positive correlations were
      observed between fibrinogen-containing ICs and anti-citrullinated fibrinogen
      autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical
      characteristics. Immunohistochemical staining demonstrated co-localisation of
      fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass
      spectrometry analysis of immune complexes immunoprecipitated from RA pannus
      tissue lysates demonstrated the presence of citrullinated fibrinogen. CONCLUSION:
      Circulating ICs containing citrullinated fibrinogen are present in one-half of
      anti-CCP+ RA patients, and these ICs co-localise with C3 in the rheumatoid
      synovium suggesting that they contribute to synovitis in a subset of RA patients.

PMID- 18710573
TI  - The expression of hyperpolarization activated cyclic nucleotide gated (HCN)
      channels in the rat ovary are dependent on the type of cell and the reproductive
      age of the animal: a laboratory investigation.
AB  - BACKGROUND: Aim of this study was to test the hypothesis that levels of
      hyperpolarization activated cyclic nucleotide gated channels 1 to 4 (HCN1-4) are
      linked to the reproductive age of the ovary. METHODS: Young, adult, and
      reproductively aged ovaries were collected from Sprague-Dawley rats. RT-PCR and
      western blot analysis of ovaries was performed to investigate the presence of
      mRNA and total protein for HCN1-4. Immunohistochemistry with semiquantitative H
      score analysis was performed using whole ovarian histologic sections. RESULTS: RT
      PCR analysis showed the presence of mRNA for HCN1-4. Western blot analysis
      revealed HCN1-3 proteins in all ages of ovarian tissues. Immunohistochemistry
      with H score analysis demonstrated distinct age-related changes in patterns of
      HCN1-3 in the oocytes, granulosa cells, theca cells, and corpora lutea. HCN4 was
      present only in the oocytes, with declining levels during the reproduction
      lifespan. CONCLUSION: The evidence presented here demonstrates cell-type and
      developmental age patterns of HCN1-4 channel expression in rat ovaries. Based on
      this, we hypothesize that HCN channels have functional significance in rat
      ovaries and may have changing roles in reproductive aging.

PMID- 18710574
TI  - Sampling 'hard-to-reach' populations in health research: yield from a study
      targeting Americans living in Canada.
AB  - BACKGROUND: Some populations targeted in survey research can be hard to reach,
      either because of lack of contact information, or non-existent databases to
      inform sampling. Here, we present a methodological "case-report" of the yield of
      a multi-step survey study assessing views on health care among American emigres
      to Canada, a hard-to-reach population. METHODS: To sample this hard-to-reach
      population, we held a live media conference, supplemented by a nation-wide media
      release announcing the study. We prepared an 'op-ed' piece describing the study
      and how to participate. We paid for advertisements in 6 newspapers. We sent the
      survey information to targeted organizations. And lastly, we asked those who
      completed the web survey to send the information to others. We use descriptive
      statistics to document the method's yield. RESULTS: The combined media strategies
      led to 4 television news interviews, 10 newspaper stories, 1 editorial and 2
      radio interviews. 458 unique individuals accessed the on-line survey, among whom
      310 eligible subjects provided responses to the key study questions. Fifty-six
      percent reported that they became aware of the survey via media outlets, 26% by
      word of mouth, and 9% through both the media and word of mouth. CONCLUSION: Our
      multi-step communication method yielded a sufficient sample of Americans living
      in Canada. This combination of paid and unpaid media exposure can be considered
      by others as a unique methodological approach to identifying and sampling hard-to
      reach populations.

PMID- 18710575
TI  - Accuracy of diagnostic registers and management of chronic obstructive pulmonary
      disease: the Devon primary care audit.
AB  - BACKGROUND: Guidelines on COPD diagnosis and management encourage primary care
      physicians to detect the disease at an early stage and to treat patients
      according to their condition and needs. Problems in guideline implementation
      include difficulties in diagnosis, using spirometry and the disputed role of
      reversibility testing. These lead to inaccurate diagnostic registers and
      inadequacy of administered treatments. This study represents an audit of COPD
      diagnosis and management in primary care practices in Devon. METHODS: Six hundred
      and thirty two patients on COPD registers in primary care practices were seen by
      a visiting Respiratory Specialist Nurse. Diagnoses were made according to the
      NICE guidelines. Reversibility testing was carried out either routinely or based
      on clinical indication in two sub-samples. Dyspnoea was assessed. Data were
      entered into a novel IT-based software which computed guideline-based treatment
      recommendations. Current and recommended treatments were compared. RESULTS: Five
      hundred and eighty patients had spirometry. Diagnoses of COPD were confirmed in
      422 patients (73%). Thirty nine patients were identified as asthma only, 94 had
      normal spirometry, 23 were restrictive and 2 had a cardiac disorder.
      Reversibility testing changed diagnosis of 11% of patients with airflow
      obstruction, and severity grading in 18%. Three quarters of patients with COPD
      had been offered practical help with smoking cessation. Short and long-acting
      anticholinergics and long acting beta-2 agonists had been under-prescribed; in 15
      18% of patients they were indicated but not received. Inhaled steroids had been
      over-prescribed (recommended in 17%; taken by 60%), whereas only 4% of patients
      with a chronic productive cough were receiving mucolytics. Pulmonary
      rehabilitation was not available in some areas and was under-used in other areas.
      CONCLUSION: Diagnostic registers of COPD in primary care contain mistakes leading
      to inaccurate prevalence estimates and inappropriate treatment decisions. Use of
      pre-bronchodilator readings for diagnosis overestimates the prevalence and
      severity in a significant minority, thus post bronchodilator readings should be
      used. Management of stable COPD does often not correspond to guidelines. The IT
      system used in this study has the potential to improve diagnosis and management
      of COPD in primary care.

PMID- 18710576
TI  - Family meetings in palliative care: Multidisciplinary clinical practice
      guidelines.
AB  - BACKGROUND: Support for family carers is a core function of palliative care.
      Family meetings are commonly recommended as a useful way for health care
      professionals to convey information, discuss goals of care and plan care
      strategies with patients and family carers. Yet it seems there is insufficient
      research to demonstrate the utlility of family meetings or the best way to
      conduct them. This study sought to develop multidisciplinary clinical practice
      guidelines for conducting family meetings in the specialist palliative care
      setting based on available evidence and consensus based expert opinion. METHODS:
      The guidelines were developed via the following methods: (1) A literature review;
      (2) Conceptual framework; (3) Refinement of the guidelines based on feedback from
      an expert panel and focus groups with multidisciplinary specialists from three
      palliative care units and three major teaching hospitals in Melbourne, Australia.
      RESULTS: The literature review revealed that no comprehensive exploration of the
      conduct and utility of family meetings in the specialist palliative care setting
      has occurred. Preliminary clinical guidelines were developed by the research
      team, based on relevant literature and a conceptual framework informed by: single
      session therapy, principles of therapeutic communication and models of coping and
      family consultation. A multidisciplinary expert panel refined the content of the
      guidelines and the applicability of the guidelines was then assessed via two
      focus groups of multidisciplinary palliative care specialists. The complete
      version of the guidelines is presented. CONCLUSION: Family meetings provide an
      opportunity to enhance the quality of care provided to palliative care patients
      and their family carers. The clinical guidelines developed from this study offer
      a framework for preparing, conducting and evaluating family meetings. Future
      research and clinical implications are outlined.

PMID- 18710577
TI  - Plasmodium knowlesi in humans, macaques and mosquitoes in peninsular Malaysia.
AB  - BACKGROUND: Since a large focus of human infection with Plasmodium knowlesi, a
      simian malaria parasite naturally found in long-tailed and pig tailed macaques,
      was reported in Sarawak, Malaysian Borneo, it was pertinent to study the
      situation in peninsular Malaysia. A study was thus initiated to screen human
      cases of Plasmodium malariae using molecular techniques, to determine the
      presence of P. knowlesi in non- human primates and to elucidate its vectors.
      METHODS: Nested polymerase chain reaction (PCR) was used to identify all
      Plasmodium species present in the human blood samples sent to the Parasitology
      laboratory of Institute for Medical Research. At the same time, non-human
      primates were also screened for malaria parasites and nested PCR was carried out
      to determine the presence of P. knowlesi. Mosquitoes were collected from Pahang
      by human landing collection and monkey-baited-traps situated on three different
      levels. All mosquitoes were identified and salivary glands and midguts of
      anopheline mosquitoes were dissected to determine the presence of malaria
      parasites and nested PCR was carried out on positive glands. Sequencing of the
      csp genes were carried on P. knowlesi samples from humans, monkeys and
      mosquitoes, positive by PCR. RESULTS AND DISCUSSION: Plasmodium knowlesi was
      detected in 77 (69.37%) of the 111 human samples, 10 (6.90%) of the 145 monkey
      blood and in 2 (1.7%) Anopheles cracens. Sequence of the csp gene clustered with
      other P. knowlesi isolates. CONCLUSION: Human infection with Plasmodium knowlesi
      is occurring in most states of peninsular Malaysia. An. cracens is the main
      vector. Economic exploitation of the forest is perhaps bringing monkeys,
      mosquitoes and humans into increased contact. A single bite from a mosquito
      infected with P. knowlesi is sufficient to introduce the parasite to humans.
      Thus, this zoonotic transmission has to be considered in the future planning of
      malaria control.

PMID- 18710578
TI  - Health related quality of life measured by SF-36: a population-based study in
      Shanghai, China.
AB  - BACKGROUND: Health related quality of life (HRQL) is a research topic that has
      attracted increasing interests around the world over the past two decades. The 36
      item Short Form (SF-36) is a commonly used instrument for measuring HRQL.
      However, the information on Chinese adults' quality of life is limited. This
      paper reports on the feasibility of using the Mandarin version of SF-36 to
      evaluate HRQL in the population of Shanghai, China. METHODS: A total of 1034
      subjects were randomly sampled using a stratified multiple-stage sampling method
      in Shanghai. Demographic information was collected, and SF-36 was used to measure
      HRQL. RESULTS: Internal reliability coefficients were greater than 0.7 in six of
      the eight SF-36 dimensions, except social function and mental health. Intraclass
      correlation coefficients ranged from 0.689 to 0.972. Split-half reliability
      coefficients were higher than 0.9 in five SF-36 dimensions. Validity was assessed
      by factor analysis and correlation analysis. Our results were basically in
      accordance with the theoretical construction of SF-36. The average scores of most
      SF-36 dimensions were higher than 80. The primary influencing risk factors of
      HRQL included chronic diseases, age, frequency of activities, and geographical
      region, which were identified using multivariate stepwise regression. CONCLUSION:
      Overall, HRQL in the population of Shanghai is quite good. The Mandarin version
      of SF-36 is a valid and reliable tool for assessing HRQL.

PMID- 18710579
TI  - Self-help interventions for depressive disorders and depressive symptoms: a
      systematic review.
AB  - BACKGROUND: Research suggests that depressive disorders exist on a continuum,
      with subthreshold symptoms causing considerable population burden and increasing
      individual risk of developing major depressive disorder. An alternative strategy
      to professional treatment of subthreshold depression is population promotion of
      effective self-help interventions that can be easily applied by an individual
      without professional guidance. The evidence for self-help interventions for
      depressive symptoms is reviewed in the present work, with the aim of identifying
      promising interventions that could inform future health promotion campaigns or
      stimulate further research. METHODS: A literature search for randomised
      controlled trials investigating self-help interventions for depressive disorders
      or depressive symptoms was performed using PubMed, PsycINFO and the Cochrane
      Database of Systematic Reviews. Reference lists and citations of included studies
      were also checked. Studies were grouped into those involving participants with
      depressive disorders or a high level of depressive symptoms, or non-clinically
      depressed participants not selected for depression. A number of exclusion
      criteria were applied, including trials with small sample sizes and where the
      intervention was adjunctive to antidepressants or psychotherapy. RESULTS: The
      majority of interventions searched had no relevant evidence to review. Of the 38
      interventions reviewed, the ones with the best evidence of efficacy in depressive
      disorders were S-adenosylmethionine, St John's wort, bibliotherapy, computerised
      interventions, distraction, relaxation training, exercise, pleasant activities,
      sleep deprivation, and light therapy. A number of other interventions showed
      promise but had received less research attention. Research in non-clinical
      samples indicated immediate beneficial effects on depressed mood for distraction,
      exercise, humour, music, negative air ionisation, and singing; while potential
      for helpful longer-term effects was found for autogenic training, light therapy,
      omega 3 fatty acids, pets, and prayer. Many of the trials were poor quality and
      may not generalize to self-help without professional guidance. CONCLUSION: A
      number of self-help interventions have promising evidence for reducing
      subthreshold depressive symptoms. Other forms of evidence such as expert
      consensus may be more appropriate for interventions that are not feasible to
      evaluate in randomised controlled trials. There needs to be evaluation of whether
      promotion to the public of effective self-help strategies for subthreshold
      depressive symptoms could delay or prevent onset of depressive illness, reduce
      functional impairment, and prevent progression to other undesirable outcomes such
      as harmful use of substances.

PMID- 18710580
TI  - A DNA and morphology based phylogenetic framework of the ant genus Lasius with
      hypotheses for the evolution of social parasitism and fungiculture.
AB  - BACKGROUND: Ants of the genus Lasius are ecologically important and an important
      system for evolutionary research. Progress in evolutionary research has been
      hindered by the lack of a well-founded phylogeny of the subgenera, with three
      previous attempts disagreeing. Here we employed two mitochondrial genes
      (cytochrome c oxidase subunit I, 16S ribosomal RNA), comprising 1,265 bp,
      together with 64 morphological characters, to recover the phylogeny of Lasius by
      Bayesian and Maximum Parsimony inference after exploration of potential causes of
      phylogenetic distortion. We use the resulting framework to infer evolutionary
      pathways for social parasitism and fungiculture. RESULTS: We recovered two well
      supported major lineages. One includes Acanthomyops, Austrolasius, Chthonolasius,
      and Lasius pallitarsis, which we confirm to represent a seventh subgenus, the
      other clade contains Dendrolasius, and Lasius sensu stricto. The subgenus
      Cautolasius, displaying neither social parasitism nor fungiculture, probably
      belongs to the second clade, but its phylogenetic position is not resolved at the
      cutoff values of node support we apply. Possible causes for previous problems
      with reconstructing the Lasius phylogeny include use of other reconstruction
      techniques, possibly more prone to instabilities in some instances, and the
      inclusion of phylogenetically distorting characters. CONCLUSION: By establishing
      an updated phylogenetic framework, our study provides the basis for a later
      formal taxonomic revision of subgenera and for studying the evolution of various
      ecologically and sociobiologically relevant traits of Lasius, although there is
      need for future studies to include nuclear genes and additional samples from the
      Nearctic. Both social parasitism and fungiculture evolved twice in Lasius, once
      in each major lineage, which opens up new opportunities for comparative analyses.
      The repeated evolution of social parasitism has been established for other groups
      of ants, though not for temporary social parasitism as found in Lasius. For
      fungiculture, the independent emergence twice in a monophyletic group marks a
      novel scenario in ants. We present alternative hypotheses for the evolution of
      both traits, with one of each involving loss of the trait. Though less likely for
      both traits than later evolution without reversal, we consider reversal as
      sufficiently plausible to merit independent testing.

PMID- 18710583
TI  - Effect of benthic boundary layer transport on the productivity of Mono Lake,
      California.
AB  - The significance of the transport of nutrient-rich hypolimnetic water via the
      benthic boundary layer (BBL) to the productivity of Mono Lake was studied using a
      coupled hydrodynamic and ecological model validated against field data. The
      coupled model enabled us to differentiate between the role of biotic components
      and hydrodynamic forcing on the internal recycling of nutrients necessary to
      sustain primary productivity. A 4-year period (1991-1994) was simulated in which
      recycled nutrients from zooplankton excretion and bacterially-mediated
      mineralization exceeded sediment fluxes as the dominant source for primary
      productivity. Model outputs indicated that BBL transport was responsible for a
      53% increase in the flux of hypolimnetic ammonium to the photic zone during
      stratification with an increase in primary production of 6% and secondary
      production of 5%. Although the estimated impact of BBL transport on the
      productivity of Mono Lake was not large, significant nutrient fluxes were
      simulated during periods when BBL transport was most active.

PMID- 18710581
TI  - Functional imaging of interleukin 1 beta expression in inflammatory process using
      bioluminescence imaging in transgenic mice.
AB  - BACKGROUND: Interleukin 1 beta (IL-1beta) plays an important role in a number of
      chronic and acute inflammatory diseases. To understand the role of IL-1beta in
      disease processes and develop an in vivo screening system for anti-inflammatory
      drugs, a transgenic mouse line was generated which incorporated the transgene
      firefly luciferase gene driven by a 4.5-kb fragment of the human IL-1beta gene
      promoter. Luciferase gene expression was monitored in live mice under anesthesia
      using bioluminescence imaging in a number of inflammatory disease models.
      RESULTS: In a LPS-induced sepsis model, dramatic increase in luciferase activity
      was observed in the mice. This transgene induction was time dependent and
      correlated with an increase of endogenous IL-1beta mRNA and pro-IL-1beta protein
      levels in the mice. In a zymosan-induced arthritis model and an oxazolone-induced
      skin hypersensitivity reaction model, luciferase expression was locally induced
      in the zymosan injected knee joint and in the ear with oxazolone application,
      respectively. Dexamethasone suppressed the expression of luciferase gene both in
      the acute sepsis model and in the acute arthritis model. CONCLUSION: Our data
      suggest that the transgenic mice model could be used to study transcriptional
      regulation of the IL-1beta gene expression in the inflammatory process and
      evaluation the effect of anti-inflammatory drug in vivo.

PMID- 18710582
TI  - Trichinella spiralis: nurse cell formation with emphasis on analogy to muscle
      cell repair.
AB  - Trichinella infection results in formation of a capsule in infected muscles. The
      capsule is a residence of the parasite which is composed of the nurse cell and
      fibrous wall. The process of nurse cell formation is complex and includes
      infected muscle cell response (de-differentiation, cell cycle re-entry and
      arrest) and satellite cell responses (activation, proliferation and
      differentiation). Some events that occur during the nurse cell formation are
      analogous to those occurring during muscle cell regeneration/repair. This article
      reviews capsule formation with emphasis on this analogy.

PMID- 18710584
TI  - Primary hepatic lymphoma presenting as fulminant hepatic failure with
      hyperferritinemia: a case report.
AB  - INTRODUCTION: Primary hepatic lymphoma is an unusual form of non-Hodgkin's
      lymphoma that usually presents with constitutional symptoms, hepatomegaly and
      signs of cholestatic jaundice. Diffuse hepatic infiltration is uncommon and
      presentation with acute hepatic failure even more rare. The presence of markedly
      elevated ferritin levels can complicate the evaluation process and suggest
      alternative diagnoses.We present the case of a middle-aged woman exhibiting
      pancytopenia, hyperferritinemia and rapidly deteriorating to develop acute
      hepatic failure. Her initial clinical picture led to a working diagnosis of adult
      onset Still's disease with probable hemophagocytic syndrome before her worsening
      liver function necessitated a percutaneous liver biopsy and establishment of the
      final diagnosis of primary hepatic lymphoma. CONCLUSION: Primary hepatic lymphoma
      is an uncommon malignancy and its manifestation as progressive hepatitis or acute
      fulminant hepatic failure can be difficult to diagnose. The presence of
      constitutional symptoms, pancytopenia and high ferritin levels can complicate the
      evaluation process. A liver biopsy early in the course of liver dysfunction may
      establish the diagnosis without a higher risk of bleeding complications seen once
      liver failure sets in.

PMID- 18710585
TI  - Assignment of Streptococcus agalactiae isolates to clonal complexes using a small
      set of single nucleotide polymorphisms.
AB  - BACKGROUND: Streptococcus agalactiae (Group B Streptococcus (GBS)) is an
      important human pathogen, particularly of newborns. Emerging evidence for a
      relationship between genotype and virulence has accentuated the need for
      efficient and well-defined typing methods. The objective of this study was to
      develop a single nucleotide polymorphism (SNP) based method for assigning GBS
      isolates to multilocus sequence typing (MLST)-defined clonal complexes. RESULTS:
      It was found that a SNP set derived from the MLST database on the basis of
      maximization of Simpsons Index of Diversity provided poor resolution and did not
      define groups concordant with the population structure as defined by eBURST
      analysis of the MLST database. This was interpreted as being a consequence of low
      diversity and high frequency horizontal gene transfer. Accordingly, a different
      approach to SNP identification was developed. This entailed use of the "Not-N"
      bioinformatic algorithm that identifies SNPs diagnostic for groups of known
      sequence variants, together with an empirical process of SNP testing. This
      yielded a four member SNP set that divides GBS into 10 groups that are concordant
      with the population structure. A fifth SNP was identified that increased the
      sensitivity for the clinically significant clonal complex 17 to 100%. Kinetic PCR
      methods for the interrogation of these SNPs were developed, and used to genotype
      116 well characterized isolates. CONCLUSION: A five SNP method for dividing GBS
      into biologically valid groups has been developed. These SNPs are ideal for high
      throughput surveillance activities, and combining with more rapidly evolving loci
      when additional resolution is required.

PMID- 18710586
TI  - Salvaging Affymetrix probes after probe-level re-annotation.
AB  - BACKGROUND: Affymetrix GeneChips can be re-annotated at the probe-level by
      breaking up the original probe-sets and recomposing new probe-sets based on up-to
      date genomic knowledge, such as available in Entrez Gene. This results in custom
      Chip Description Files (CDF). Using these custom CDFs improves the quality of the
      data and thus the results of related gene expression studies. However, 44-71% of
      the probes on a GeneChip are lost in this re-annotation process. Although
      generally aimed at less known genes, losing these probes obviously means a
      substantial loss of expensive experiment data. Biologists are therefore very
      reluctant to adopt this approach. FINDINGS: We aimed to re-introduce the non
      affected Affymetrix probe-sets after these re-annotation procedures. For this, we
      developed an algorithm (CDF-Merger) and applied it to standard Affymetrix CDFs
      and custom Brainarray CDFs to obtain Hybrid CDFs. Thus, salvaging lost Affymetrix
      probes with our CDF-Merger restored probe content up to 94%. Because the salvaged
      probes (up to 54% of the probe content on the arrays) represent less-reliable
      probe-sets, we made the origin of all probe-set definitions traceable, so
      biologists can choose at any time in their analyses, which subset of probe-sets
      they want to use. CONCLUSION: The availability of up-to-date Hybrid CDFs plus R
      environment allows for easy implementation of our approach.

PMID- 18710587
TI  - Variation in breast cancer risk in BRCA1 and BRCA2 mutation carriers.
AB  - Genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations can provide important
      information for women who are concerned about their breast and ovarian cancer
      risks and need to make relevant prevention and medical management decisions.
      However, lifetime risks of breast cancer in individual BRCA1/2 mutation carriers
      have been confusing to apply in clinical decision-making. Published risk
      estimates vary significantly and are very dependent on the characteristics of the
      population under study. Recently, Begg and colleagues estimated cancer risks in a
      population-based study of BRCA1/2 mutation carriers. Here, we discuss the
      clinical decision-making implications of this research in the context of risk
      factors that may influence risk estimates in BRCA1/2 mutation carriers.

PMID- 18710588
TI  - Drug-therapy networks and the prediction of novel drug targets.
AB  - A recent study in BMC Pharmacology presents a network of drugs and the therapies
      in which they are used. Network approaches open new ways of predicting novel drug
      targets and overcoming the cellular robustness that can prevent drugs from
      working.

PMID- 18710591
TI  - Altered fractalkine cleavage results in an organ-specific 17 kDa fractalkine
      fragment in salivary glands of NOD mice.
AB  - Sjogren's syndrome is a rheumatic disease in which the salivary and lacrimal
      glands are the principal targets of a pathological autoimmune reaction. Previous
      studies in mice indicated that delayed organogenesis and aberrant cell physiology
      followed by an increase in acinar cell apoptosis precede chronic focal
      inflammation in the salivary glands and the manifestation of impaired exocrine
      gland secretion. In a recent study by Wildenberg and colleagues, the authors
      report aberrant proteolytic activity in the salivary glands of non-obese diabetic
      mice and the generation of a unique organ-specific 17 kDa fragment of the
      chemokine and adhesion molecule fractalkine.

PMID- 18710589
TI  - High avidity autoreactive T cells with a low signalling capacity through the T
      cell receptor: central to rheumatoid arthritis pathogenesis?
AB  - Self-reactive T cells with low signalling capacity through the T-cell receptor
      were recently observed in the SKG mouse model of rheumatoid arthritis (RA) and
      have been linked to a spontaneous mutation in the ZAP-70 signal transduction
      molecule. Here we hypothesize that similar mechanisms also drive RA, associated
      with an abnormal innate and adaptive immune response driven by nuclear factor
      kappaB activation and tumour necrosis factor secretion. Similar to the essential
      role played by pathogens in SKG mice, we propose that HLA-associated immunity to
      chronic viral infection is a key factor in the immune dysregulation and joint
      inflammation that characterize RA.

PMID- 18710592
TI  - Sepsis therapy: what's the best for the mitochondria?
AB  - It is suspected that mitochondrial dysfunction is a major cause of organ failure
      in sepsis and septic shock. A study presented in this issue of Critical Care
      revealed that liver mitochondria from pigs treated with norepinephrine during
      endotoxaemia exhibit greater in vitro respiratory activity. The investigators
      provide an elegant demonstration of how therapeutic interventions in sepsis may
      profoundly influence mitochondrial respiration, but many aspects of mitochondrial
      function in sepsis remain to be clarified.

PMID- 18710594
TI  - DNA replication can still spring surprises.

PMID- 18710593
TI  - Clinical review: liberation from mechanical ventilation.
AB  - Mechanical ventilation is the defining event of intensive care unit (ICU)
      management. Although it is a life saving intervention in patients with acute
      respiratory failure and other disease entities, a major goal of critical care
      clinicians should be to liberate patients from mechanical ventilation as early as
      possible to avoid the multitude of complications and risks associated with
      prolonged unnecessary mechanical ventilation, including ventilator induced lung
      injury, ventilator associated pneumonia, increased length of ICU and hospital
      stay, and increased cost of care delivery. This review highlights the recent
      developments in assessing and testing for readiness of liberation from mechanical
      ventilation, the etiology of weaning failure, the value of weaning protocols, and
      a simple practical approach for liberation from mechanical ventilation.

PMID- 18710595
TI  - Is "safe effective glucose control" effective and safe?

PMID- 18710596
TI  - Music, memory and emotion.
AB  - Because emotions enhance memory processes and music evokes strong emotions, music
      could be involved in forming memories, either about pieces of music or about
      episodes and information associated with particular music. A recent study in BMC
      Neuroscience has given new insights into the role of emotion in musical memory.

PMID- 18710599
TI  - Human genetics branches out in Barcelona.

PMID- 18710600
TI  - Suppression of bone morphogenetic protein inhibitors promotes osteogenic
      differentiation: therapeutic implications.
AB  - Bone morphogenetic proteins (BMPs) are expressed during osteogenesis and their
      action is regulated by corresponding BMP inhibitors. Chordin (a well recognized
      BMP inhibitor) and BMP-2 are expressed during osteogenic differentiation of human
      mesenchymal stem cells. Chordin inhibition induces human mesenchymal stem cell
      differentiation and reduces their proliferation by increasing BMP-2
      bioavailability. The potential of suppressing BMP inhibitors is emerging as a
      biological therapeutic target in bone tissue engineering, because it results in
      an unopposed synergy between the various growth factors that are involved in
      osteogenesis, within their physiological milieu.

PMID- 18710598
TI  - Multifunctional roles of insulin-like growth factor binding protein 5 in breast
      cancer.
AB  - The insulin-like growth factor axis, which has been shown to protect cells from
      apoptosis, plays an essential role in normal cell physiology and in cancer
      development. The family of insulin-like growth factor binding proteins (IGFBPs)
      has been shown to have a diverse spectrum of functions in cell growth, death,
      motility, and tissue remodeling. Among the six IGFBP family members, IGFBP-5 has
      recently been shown to play an important role in the biology of breast cancer,
      especially in breast cancer metastasis; however, the exact mechanisms of action
      remain obscure and sometimes paradoxical. An in-depth understanding of IGFBP-5
      would shed light on its potential role as a target for breast cancer
      therapeutics.

PMID- 18710601
TI  - Role of the eosinophil count in discriminating the severity of community-acquired
      pneumonia in HIV-infected patients.

PMID- 18710602
TI  - Cobalamin deficiency results in an abnormal increase in L-methylmalonyl-co-enzyme
      A mutase expression in rat liver and COS-7 cells.
AB  - The aim of the present study was to examine the effects of cobalamin (Cbl) on the
      activity and expression of L-methylmalonyl-CoA mutase (MCM) in rat liver and
      cultured COS-7 cells. The MCM holoenzyme activity was less than 5% of the total
      (holoenzyme+apoenzyme) activity in the liver although rats were fed a diet
      containing sufficient Cbl. When weanling rats were maintained on a Cbl-deficient
      diet, the holo-MCM activity became almost undetectable at the age of 10 weeks. In
      contrast, a marked increase in the total-MCM activity occurred under the Cbl
      deficient conditions, and at the age of 20 weeks it was about 3-fold higher in
      the deficient rats than in the controls (108 (SD 14.5) v. 35 (SD 8.5) nmol/mg
      protein per min (n 5); P<0.05). Western blot analysis confirmed that the MCM
      protein level increased significantly in the Cbl-deficient rats. However, the MCM
      mRNA level, determined by real-time PCR, was rather decreased. When COS-7 cells
      were cultured in a medium in which 10% fetal bovine serum was the sole source of
      Cbl, holo-MCM activity was barely detected. The supplementation of Cbl resulted
      in a large increase in the holo-MCM activity in the cells, but the activity did
      not exceed 30% of the total-MCM activity even in the presence of Cbl at 10
      micromol/l. In contrast, the total-MCM activity was significantly decreased by
      the Cbl supplementation, indicating that Cbl deficiency results in an increase in
      the MCM protein level in COS-7 cells as well as in rat liver.

PMID- 18710603
TI  - Absorption, metabolism and excretion of flavanones from single portions of orange
      fruit and juice and effects of anthropometric variables and contraceptive pill
      use on flavanone excretion.
AB  - Oranges are rich sources of flavonoids that are bioactive and may protect against
      age-related diseases. The absorption of orange flavanones may be affected by
      factors such as processing and subject anthropometric variables, and the
      bioactivity of the absorbed phytochemicals depends on how they are metabolised
      during absorption. In a randomised cross-over study, twenty subjects consumed a
      single portion of orange fruit (150 g) or juice (300 g) that contained the
      flavanones narirutin and hesperidin, and an additional 109 subjects across a
      broad age range (18-80 years) consumed the juice. Flavanone metabolites were
      measured in regularly collected samples of plasma and urine. After consumption of
      fruit or juice, flavanone conjugates, but not the aglycones, were detected in
      plasma and urine. The flavanone conjugates were shown to include the 7- and 4'-O
      monoglucuronides of naringenin, the 7- and 3'-O-monoglucuronides of hesperetin,
      two hesperetin diglucuronides and a hesperetin sulfo-glucuronide, but no
      aglycones or rutinosides. Analysis of the plasma pharmacokinetic and urinary
      excretion data on a dose-adjusted basis indicated no difference in absorption or
      excretion of either flavanone between the fruit and juice matrices. In the
      extended urinary excretion dataset the individual variation was very large (range
      0-59 % urinary yield). There was a small but significant (P < 0.05) decrease in
      the excretion of hesperetin (but not naringenin) with increasing age (P < 0.05),
      but the effects of sex, BMI and contraceptive pill use were shown not to be
      associated with the variation in flavanone excretion.

PMID- 18710604
TI  - Flaxseed oil prevents trans-10, cis-12-conjugated linoleic acid-induced insulin
      resistance in mice.
AB  - Insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) are found
      in 35 and 30 % of US adults, respectively. Trans-10, cis-12-conjugated linoleic
      acid (CLA) has been found to cause both these disorders in several animal models.
      We hypothesised that IR and NAFLD caused by CLA result from n-3 fatty acid
      deficiency. Pathogen-free C57BL/6N female mice (aged 8 weeks; n 10) were fed
      either a control diet or diets containing trans-10, cis-12-CLA (0.5 %) or
      CLA+flaxseed oil (FSO) (0.5 %+0.5 %) for 8 weeks. Weights of livers,
      concentration of circulating insulin, values of homeostatic model 1 (HOMA1) for
      IR and HOMA1 for beta cell function were higher by 160, 636, 985 and 968 % in the
      CLA group compared with those in the control group. FSO decreased fasting glucose
      by 20 % and liver weights by 37 % compared with those in the CLA group; it
      maintained circulating insulin, HOMA1-IR and HOMA1 for beta cell function at
      levels found in the control group. CLA supplementation decreased n-6 and n-3 wt%
      concentrations of liver lipids by 57 and 73 % and increased the n-6:n-3 ratio by
      58 % compared with corresponding values in the control group. FSO increased n-6
      and n-3 PUFA in liver lipids by 33 and 342 % and decreased the n-6:n-3 ratio by
      70 % compared with corresponding values in the CLA group. The present results
      suggest that some adverse effects of CLA may be due to n-3 PUFA deficiency and
      that these can be corrected by a concomitant increase in the intake of alpha
      linolenic acid, 18 : 3n-3.

PMID- 18710605
TI  - The effects of a reduced-sodium, high-potassium salt substitute on food taste and
      acceptability in rural northern China.
AB  - A potassium chloride-containing salt substitute lowers blood pressure levels, but
      its overall acceptability has been of concern due to its potential adverse
      effects on food taste. In a large-scale, blinded randomised trial evaluating the
      comparative effects of a salt substitute (65 % sodium chloride, 25 % potassium
      chloride and 10 % magnesium sulphate) and a normal salt (100 % sodium chloride)
      on blood pressure, we collected data on the saltiness, flavour and overall
      acceptability of food. We performed this at baseline, 1, 6 and 12 months post
      randomisation using 100 mm visual analogue scales for assessments of both home
      cooked foods and a standard salty soup. The mean age of the 608 participants from
      rural northern China was 60 years and 56 % of them were females. In the primary
      analyses, the changes in the saltiness, flavour and overall acceptability of both
      home-cooked foods and a standard salty soup were not different between the
      randomised groups (all P>0.08). In the secondary analyses, weighting each of the
      data points according to the lengths of the respective follow-up intervals, the
      flavour of both home-cooked foods (mean difference = - 1.8 mm, P = 0.045) and a
      standard salty soup (mean difference = - 1.9 mm, P = 0.03) was slightly weaker in
      the salt substitute group. We conclude that salt substitution is both an
      effective and an acceptable means of blood pressure control. Possible small
      differences in flavour did not importantly deter the use of the salt substitute
      in this study group, although the acceptability of the salt substitute by a more
      general population group would need to be confirmed.

PMID- 18710606
TI  - Effects of dietary supplementation with the green tea polyphenol epigallocatechin
      3-gallate on insulin resistance and associated metabolic risk factors: randomized
      controlled trial.
AB  - Animal evidence indicates that green tea may modulate insulin sensitivity, with
      epigallocatechin-3-gallate (EGCG) proposed as a likely health-promoting
      component. The purpose of this study was to investigate the effect of dietary
      supplementation with EGCG on insulin resistance and associated metabolic risk
      factors in man. Overweight or obese male subjects, aged 40-65 years, were
      randomly assigned to take 400 mg capsules of EGCG (n 46) or the placebo lactose
      (n 42), twice daily for 8 weeks. Oral glucose tolerance testing and measurement
      of metabolic risk factors (BMI, waist circumference, percentage body fat, blood
      pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG) was conducted
      pre- and post-intervention. Mood was evaluated weekly using the University of
      Wales Institute of Science and Technology mood adjective checklist. EGCG
      treatment had no effect on insulin sensitivity, insulin secretion or glucose
      tolerance but did reduce diastolic blood pressure (mean change: placebo - 0.058
      (se 0.75) mmHg; EGCG - 2.68 (se 0.72) mmHg; P = 0.014). No significant change in
      the other metabolic risk factors was observed. The EGCG group also reported
      feeling in a more positive mood than the placebo group across the intervention
      period (mean score for hedonic tone: EGCG, 29.11 (se 0.44); placebo, 27.84 (se
      0.46); P = 0.048). In conclusion, regular intake of EGCG had no effect on insulin
      resistance but did result in a modest reduction in diastolic blood pressure. This
      antihypertensive effect may contribute to some of the cardiovascular benefits
      associated with habitual green tea consumption. EGCG treatment also had a
      positive effect on mood. Further studies are needed to confirm the findings and
      investigate their mechanistic basis.

PMID- 18710607
TI  - Effects of increasing docosahexaenoic acid intake in human healthy volunteers on
      lymphocyte activation and monocyte apoptosis.
AB  - Dietary intake of long-chain n-3 PUFA has been reported to decrease several
      markers of lymphocyte activation and modulate monocyte susceptibility to
      apoptosis. However, most human studies examined the combined effect of DHA and
      EPA using relatively high daily amounts of n-3 PUFA. The present study
      investigated the effects of increasing doses of DHA added to the regular diet of
      human healthy volunteers on lymphocyte response to tetradecanoylphorbol acetate
      plus ionomycin activation, and on monocyte apoptosis induced by oxidized LDL.
      Eight subjects were supplemented with increasing daily doses of DHA (200, 400,
      800, 1600 mg) in a TAG form containing DHA as the only PUFA, for 2 weeks each
      dose. DHA intake dose-dependently increased the proportion of DHA in mononuclear
      cell phospholipids, the augmentation being significant after 400 mg DHA/d. The
      tetradecanoylphorbol acetate plus ionomycin-stimulated IL-2 mRNA level started to
      increase after ingestion of 400 mg DHA/d, with a maximum after 800 mg intake, and
      was positively correlated (P < 0.003) with DHA enrichment in cell phospholipids.
      The treatment of monocytes by oxidized LDL before DHA supplementation drastically
      reduced mitochondrial membrane potential as compared with native LDL treatment.
      Oxidized LDL apoptotic effect was significantly attenuated after 400 mg DHA/d and
      the protective effect was maintained throughout the experiment, although to a
      lesser extent at higher doses. The present results show that supplementation of
      the human diet with low DHA dosages improves lymphocyte activability. It also
      increases monocyte resistance to oxidized LDL-induced apoptosis, which may be
      beneficial in the prevention of atherosclerosis.

PMID- 18710608
TI  - Consumption of mate tea (Ilex paraguariensis) decreases the oxidation of
      unsaturated fatty acids in mouse liver.
AB  - Mate (Ilex paraguariensis) is rich in polyphenolic compounds, which are thought
      to contribute to the health benefits of tea. Mate tea was administered orally to
      mice at a dose of 0.5, 1.0 or 2.0 g/kg for 60 d, and changes both in serum lipid
      concentration and fatty acid composition of liver and kidney were examined. The
      effects of mate tea on serum and tissue lipid peroxidation were assessed by the
      evaluation of thiobarbituric acid-reactive substances (TBARS). In tea-consuming
      mice, both MUFA (18:1n-9) and PUFA (18:2n-6 and 20:4n-6) were increased (P<0.05)
      in the liver lipid (approximately 90 and 60%, respectively), whereas only MUFA
      (approximately 20%) were increased in the kidney lipid. The most altered PUFA
      class was n-6 PUFA, which increased by approximately 60-75 % (P<0.05). This
      difference in the fatty acid profile in the liver is reflected in the increased
      PUFA:SFA ratio. Consistent with these results, mice fed with mate tea had much
      lower TBARS in the liver. No differences (P>0.05) were found in the levels of
      serum cholesterol, HDL-cholesterol and TAG under the conditions of the present
      study. These results suggest that treatment with mate tea was able to protect
      unsaturated fatty acids from oxidation and may have selective protective effects
      within the body, especially on the liver.

PMID- 18710609
TI  - [Molecular target therapy: a milestone on the road for curing cancer].
AB  - Molecular target therapy (MTT), using chemicals of low molecular weight,
      monoclonal antibodies, and/or polypeptides to interfere with specific signal
      pathways in cancer cells, causes inhibition of tumor progression. Clinical
      evidence has demonstrated that MTT has promising potential in not only killing
      tumors but also inducing tumor cells differentiate into normal cells, leading to
      cure of the patients. Furthermore, MTT leads to potent inhibition of oncogenic
      signals. The delay of tumor progression makes the patients "survival with tumor".
      Thus, in the future it is possible that cancer become a chronic disease much like
      diabetes and hypertension. This article reviewed the theory on molecular target
      therapy, its features and future direction.

PMID- 18710610
TI  - [Effect of starvation-induced autophagy on cell cycle of tumor cells].
AB  - BACKGROUND & OBJECTIVE: No serum starvation could induce autophagy and cell cycle
      arrest. Although autophagy and cell cycle have been widely explored, little is
      known about their relationship. This study was to observe the change of Cyclin
      expression during starvation-induced autophagy to discuss the effect of autophagy
      on cell cycle. METHODS: In control group, HeLa cells were treated with d-Hanks
      solution (a medium with no serum). In experiment group, HeLa cells were treated
      with d-Hanks solution containing 3-methyladenine (3-MA, a specific inhibitor of
      autophagy). Cells were harvested after being starved for 0, 3, 6 and 12 h. Flow
      cytometry (FCM) and Weston blot were used to detect Cyclin and microtubule
      associated protein 1 light chain 3(LC-3) which marked autophagy specifically.
      RESULTS: In control group, the expression of LC-3 protein was detected early
      after being starved for 3 h, and gradually increased along with starvation; the
      expression of Cyclin D3 and Cyclin E was decreased evidently after a short-time
      starvation (3 h) and descended to the minimum when cells were being starved for 6
      h; the expression of Cyclin A and Cyclin B1 were apparently decreased after being
      starved for 6 h. In experiment group, LC-3 protein could not be detected during
      starvation when cells were exposed to 3-MA and the down-regulation of Cyclins was
      suppressed. CONCLUSIONS: Autophagy is involved in starvation-induced hydrolysis
      of Cyclins. The hydrolysis of Cyclin D3 and Cyclin E is quicker than that of
      Cyclin A and Cyclin B1.

PMID- 18710611
TI  - [Effects of FRZB on growth and metastasis of gastric cancer cell line SGC-7901].
AB  - BACKGROUND & OBJECTIVE: FRZB (frizzled motif associated with bone development), a
      member of the secreted frizzled related protein (sFRP) family, plays an important
      role in embryonic development. The expression of FRZB can suppress the invasion
      ability of prostate cancer by inhibiting the expression of matrix
      metalloproteinase-2 (MMP-2) and MMP-9. This study was to investigate the effects
      of FRZB on tumorigenicity and metastasis of gastric cancer cell line SGC-7901.
      METHODS: FRZB expression vector and empty vector were constructed and transfected
      into SGC-7901 cells to obtain stable clones (SGC-7901/FRZB and SGC-7901/vector).
      Cell proliferation was detected by MTT assay. The tumorigenicity was investigated
      by soft agar colony formation test (in vitro) and xenograft mouse model (in
      vivo). The adhesive and invasive abilities of SGC-7901/FRZB cells were determined
      by Boyden chambers. The expression of MMPs in SGC-7901 cells was tested by
      immunocytochemistry. RESULTS: The expression of FRZB was increased in SGC
      7901/FRZB cells. Growth rate and colony formation rate of SGC-7901/FRZB cells
      were decreased to about 60% and 15% as compared with those of SGC-7901/vector
      cells, respectively. The rates of adhesion to collagenI, collagen IV,
      vitronectin, fibronectin and laminin were increased in SGC-7901/FRZB cells by
      12.8%, 19.8%, 59.8%, 26.7% and 15.2% as compared with those in SGC-7901/vector
      cells, respectively. The positive dyeing of MMP-2, MMP-7 and MMP-9 in SGC
      7901/FRZB cells was reduced. The numbers of invasive SGC-7901, SGC-7901/vector
      and SGC-7901/FRZB cells were 55.90+/-5.68, 54.80+/-6.97, 6.60+/-2.63,
      respectively. CONCLUSION: FRZB exhibits antitumor ability in gastric cancer cell
      line SGC-7901 in vitro and in vivo, and decreases the expression of MMP-2, MMP-7
      and MMP-9.

PMID- 18710612
TI  - [Effects of Epstein-Barr virus latent membrane protein 1 on metastasis of human
      nasopharyngeal carcinoma cell lines].
AB  - BACKGROUND & OBJECTIVE: Epstein-Barr virus (EBV)-encoded latent membrane protein
      1 (LMP1) plays an important role in the metastasis of nasopharyngeal carcinoma
      (NPC). This study was to investigate the effects of EBV LMP1 on the metastasis of
      NPC cell lines, and explore potential mechanism. METHODS: The expression of LMP1,
      E-cadherin and intercellular adhesion molecule-1 (ICAM-1) in human NPC cell lines
      CNE1 (well differentiated) and CNE1-GL (CNE1 cells transfected with LMP1) were
      detected by SP immunohistochemistry, reverse transcription-polymerase chain
      reaction (RT-PCR) and Western blot. The cell-cell adhesion assay, the cell-matrix
      adhesion assay, the wound-induced migration assay and the migration assay were
      used to investigate the effects of LMP1 on adhesive and metastatic abilities of
      NPC cells. RESULTS: The positive rates of LMP1 and ICAM-1 were significantly
      lower in CNE1 cells than in CNE1-GL cells [0% vs. (96.60+/-3.03)%, P<0.01;
      (5.27+/-1.45)% vs. (93.33+/-4.23)%, P<0.01]; the positive rate of E-cadherin was
      significantly higher in CNE1 cells than in CNE1-GL cells [(37.47+/-1.50)% vs.
      (19.53+/-1.92)%, P<0.01]. The expression of E-cadherin was significantly
      inhibited (P<0.01), while the expression of ICAM-1 was significantly increased
      (P<0.01) in CNE1-GL cells as compared with those in CNE1 cells. The cell-cell
      adhesive ability of CNE1-GL cells was lower than that of CNE1 cells (P<0.05). The
      cell-matrix adhesive ability of CNE1-GL cells was significantly higher than that
      of CNE1 cells (0.60+/-0.03 vs. 0.46+/-0.01, P<0.01). The number of migrated CNE1
      GL cells was higher than that of migrated CNE1 cells (119.3+/-6.0 vs. 46.3+/-7.0,
      P<0.05). CONCLUSION: By inhibiting E-cadherin expression and enhancing ICAM-1
      expression, LMP1 may reduce the cell-cell adhesive ability and improve the cell
      matrix adhesive ability and migratory ability of NPC cells, which may play roles
      in the invasion and metastasis of NPC.

PMID- 18710613
TI  - [Effects of mitoxantrone on the activity of human protein kinase CK2 holoenzyme].
AB  - BACKGROUND & OBJECTIVE: Protein kinase CK2, a highly conserved protein
      serine/threonine kinase that is ubiquitously distributed in eukaryotes, has a
      close relationship with human leukemia. Mitoxantrone is an effective drug used
      for acute leukemias. This study was to observe the effects of mitoxantrone on the
      activity of recombinant holoenzyme of human protein kinase CK2 and proliferation
      in human leukemia cell line HL-60. METHODS: The CK2 holoenzyme composed of alphao
      and beta subunits was recombined in vitro. Subsequently, CK2 was treated with
      mitoxantrone at various concentrations, followed by addition of reacting liquid
      containing [gamma-32P] ATP. CK2 activity was measured by detecting the
      radioactivity of 32P transferred onto the substrates of CK2. The effect of
      mitoxantrone on the proliferation of HL-60 cells was detected by the trypan blue
      dye exclusion assay; the changes in the cell cycle were analyzed by flow
      cytometry (FCM); apoptosis was analyzed by FCM and DNA agarose gel
      electrophoresis; effects of the drugs on the intrinsic CK2 activity were measured
      by a specific CK2 peptide substrate. RESULTS: Mitoxantrone strongly inhibited the
      holoenzyme activity of recombinant human protein kinase CK2 (IC50=0.66
      micromol/L). The inhibition of CKZ by mitoxantrone was competitive with respect
      to ATP (Ki 0.25 micromol/L) and mostly non-competitive with respect to casein (Ki
      0.66 micromol/L). Mitoxantrone exerted strong cytotoxicity to HL-60 cells. When
      treated with 0.1 micromol/L mitoxantrone for 12 h, the apoptotic rate of HL-60
      cells was 9.3%. Mitoxantrone did not affect intracellular CK2 activity.
      CONCLUSIONS: Mitoxantrone is a strong inhibitor of recombinant human protein
      kinase CK2 in vitro. Apoptosis induced by mitoxantrone in HL-60 cells has no
      correlation to intracellular CK2 activity.

PMID- 18710614
TI  - [Effects of trichostatin A and paclitaxel on apoptosis and mitochondrial membrane
      potential of human endometrial carcinoma Ark2 cells].
AB  - BACKGROUND & OBJECTIVE: Patients suffered from advanced endometrial cancer have
      poor prognosis. The five-year survival is only 25%. Histone deacetylase
      inhibitors have shown promise in the treatment for a variety of malignancies. In
      combination with traditional cytotoxic chemotherapy, histone deacetylase
      inhibitors can enhance the survival rate of cancer patients. This study was to
      investigate the effect and mechanism of trichostatin A (TSA), a histone
      deacetylase inhibitor, combined with paclitaxel (PTX) on the apoptosis of human
      endometrial carcinoma cell line Ark2. METHODS: Ark2 cells were cultured in RPMI
      1640 and treated with PTX alone, TSA alone or the two drugs in combination. Cell
      apoptosis was detected using Annexin V and Hoechst staining; perturbation of
      mitochondrial membrane potential was detected using MitoTracker red Poly (ADP
      ribose) polymerase; caspase-9 degradation products and tubulin acetylation were
      detected by Western blot. RESULTS: Results of Annexin V showed that PTX (1.5
      nmol/L) plus TSA (25 nmol/L) induced a significantly higher apoptotic rate
      (45.2%) than PTX alone (14.1%) or TSA alone (11.2%) did in Ark2 cells after drug
      treatment for three days. The results of Hoechst staining and Annexin V were
      consistent. A loss of mitochondrial membrane potential could activate the
      apoptotic cascade. Cleavages of PARP and caspase-9 were significantly apparent in
      PTX plus TSA group than in PTX group or TSA group (P<0.05). PTX and TSA could
      induce tubulin acetylation. PTX in combination with TSA increased acetylated
      tublins and microtubule stability compared with either drug alone. The loss of
      mitochondrial membrane potential was more dramatic in the drug combination group
      than the single drug group. The effects of TSA and PTX were synergistic (q=2.54).
      CONCLUSION: TSA and PTX could induce apoptosis of Ark2 cells, which may be
      through the loss of mitochondrial membrane potential and acetylation of non
      histone proteins induced by histone deacetylase inhibitors.

PMID- 18710615
TI  - [Overexpressing exogenous S100A13 gene and its effect on proliferation of human
      thyroid cancer cell line TT].
AB  - BACKGROUND & OBJECTIVE: S100A13 is involved in tumor formation, and is highly
      expressed in human thyroid gland. This study was to investigate the effect of
      exogenous S100A13 overexpression on the proliferation of human thyroid cancer
      cell line TT. METHODS: The eukaryotic expression plasmid pCDNA3.1/NT-GFP-S100A13
      and empty vector pCDNA3.1/NT-GFP were transfected into TT cells. The cells were
      selected by G418. The expression of green fluorescent protein (GFP) was observed
      under laser scanning microscope, and the expression of S100A13 mRNA and protein
      was detected by real-time reverse transcription-polymerase chain reaction (RT
      PCR) and Western blot. The effects of S100A13 on cell proliferation and cell
      cycle progression were measured by cell growth curve and flow cytometry. RESULTS:
      TT-S100A13-GFP and TT-GFP cells, which separately expressed S100A13 and
      pCDNA3.1/NT-GFP, were constructed successfully. TT-S100A13-GFP cells grew faster
      than TT-GFP and TT cells [(2.30+/-0.24) x 10(5) vs. (1.40+/-0.25) x 10(5) and
      (1.50+/-0.22) x 10(5) at the 7th day of cell culture, P<0.05]; both S phase
      proportion and G2/M phase proportion were significantly higher in TT-S100A13-GFP
      cells than in TT-GFP and TT cells [(6.47+/-0.14)% vs. (5.86+/-0.23)% and (5.99+/
      0.28)% at S phase, P<0.05; (50.27+/-0.66)% vs. (39.39+/-0.23)% and (39.64+/
      0.64)% at G2/M phase, P<0.05]. CONCLUSION: Exogenous S100A13 gene overexpression
      could accelerate cell proliferation, and promote cell cycle progression of TT
      cells from G0/G1 phase to S and G2/M phase.

PMID- 18710616
TI  - [Effects of sodium butyrate on proliferation and differentiation of human gastric
      carcinoma cell line AGS].
AB  - BACKGROUND & OBJECTIVE: Sodium butyrate (NaBT) can inhibit proliferation and
      induce differentiation of various tumor cells. This study was to investigate
      effects of NaBT on the proliferation and differentiation of human gastric
      carcinoma cell line AGS and explore the possible mechanism. METHODS: AGS cells
      were treated with 0, 1.0, 2.0 and 4.0 mmol/L of NaBT. Cell proliferation was
      detected by MTT assay; cell morphology changes were observed under optical and
      transmission electron microscopy; cell cycle was detected by flow cytometry
      (FCM). The expression of cyclin-dependent kinase inhibitor p21 was detected by
      reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.
      RESULTS: After incubation with different concentrations of NaBT for 24 to 72 h,
      AGS cell proliferation was inhibited dramatically and the highest inhibition rate
      was 81.54%. The structure of AGS cells changed greatly. NaBT induced an increase
      of G0/G1 phase cells and a significant decrease of S phase cells accompanied by
      the changes in DNA ploidy. The expression of p21 was up-regulated at both mRNA
      and protein levels. NaBT exerted its effects in a dose-dependent manner.
      CONCLUSIONS: NaBT could induce G1 arrest and inhibit cell proliferation in AGS
      cells by up-regulating the expression of p21. This could reverse the malignant
      phenotype of AGS to some extents.

PMID- 18710617
TI  - [Effects of manumycin combined with methoxyamine on apoptosis in myeloid leukemia
      U937 cells].
AB  - BACKGROUND & OBJECTIVE: Repair of DNA damage is important to cell survival. Our
      previous study showed DNA damage response induced by manumycin in cancer cells.
      We hypothesized that methoxyamine, an inhibitor of base-excision repair, can
      enhance the antineoplastic effect of manumycin. This study was to investigate
      apoptosis induced by manumycin combined with methoxyamine in myeloid leukemia
      cell line U937, and to explore the role of mitochondrial apoptotic pathway in
      apoptosis induction of the two drugs. METHODS: U937 cells were treated with
      various concentrations of manumycin and/or methoxyamine for 48 h. The cell
      viability was analyzed by MTT assay. Colony formation was evaluated by soft agar
      clonogenic assay. Cell apoptosis was investigated by flow cytometry. Protein
      expressions of cytochrome c, caspase-9, and poly ADP-ribose polymerase (PARP)
      were determined by Western blot. RESULTS: The dose-response curve of manumycin
      was shifted to the left after addition of methoxyamine. The combination index
      (CI) was less than 1 (P<0.05) in U937 cells (P<0.05), indicating a synergistic
      effect of manumycin and methoxyamine. Rates of colony formation of U937 cells
      treated with 1 micromol/L manumycin, or 5 mmol/L methoxyamine, or the combination
      of the two were 0.3641+/-0.0463, 0.7541+/-0.0379, and 0.0473+/-0.0024,
      respectively compared with that of control cells (P<0.05). Moreover, the drug
      combination resulted in enhanced apoptosis in U937 cells. The apoptotic rates of
      the control, manumycin, methoxyamine and combination group were (2.34+/-0.30)%,
      (8.80+/-0.95)%, (2.21+/-0.19)%, and (13.37+/-0.91)%, respectively. The
      combination of manumycin with methoxyamine also promoted the release of
      cytochrome c from mitochondria into the cytosol, activated caspase-9, and led
      appearance of specific cleavage of PARP in U937 cells. CONCLUSION: Methoxyamine
      enhances manumycin-induced apoptosis in U937 myeloid leukemia cells.

PMID- 18710618
TI  - [Observation on myeloid origin of neovascular endothelial cells and infiltration
      of bone marrow-originated inflammatory cells in a murine tumor model].
AB  - BACKGROUND & OBJECTIVE: Some studies indicate that endothelial progenitor cells
      (EPCs) originated from the bone marrow participate in neoplastic angiogenesis,
      and that bone marrow origin of inflammatory cells potentially contribute to
      neoplastic invasion, angiogenesis and metastasis. This study was to observe the
      origin of neovascular endothelial cells and infiltration of bone marrow
      originated inflammatory cells in a murine tumor model. METHODS: Healthy C57BL/6
      mice were irradiated with 60Co at 8 Gy. Bone marrow cells of green fluorescent
      protein (GFP) transgenic C57BL/6 mice (donators) were transplanted intravenously
      into C57BL/6 mice (recipients) via the tail vein 24 h after irradiation. Lewis
      lung tumor cells were inoculated subcutaneously into recipient mice 2 weeks after
      transplantation. The xenograft tumors were removed until their diameters reached
      approximately 1- 2 cm. Subsequently, tumor vessels and inflammatory cells were
      observed under fluorescent microscopy and detected using immunohistochemistry
      (IHC). RESULTS: Unsuccessive green fluorescence emitted by neoplastic vascular
      endothelial cells and inflammatory cells was observed, most of which appeared
      positive IHC staining. A large number of macrophages were observed inside or
      adjacent to the necrotic areas of the tumor. A few lymphatic cells were mainly
      dispersed inside tumor stroma and tumor cells. CONCLUSIONS: Partial endothelial
      cells of neoplastic neovessels originate from the bone marrow. The murine tumor
      model could be used as a specific and direct approach to observe bone marrow
      originated cells in neoplasms.

PMID- 18710619
TI  - [Hepatic intra-arterial bio-chemotherapy for the treatment of melanoma patients
      with liver metastasis: a phase II clinical study].
AB  - BACKGROUND & OBJECTIVE: The therapeutic effect on melanoma metastasizing to liver
      is poor. Researches have demonstrated that hepatic intra-arterial bio
      chemotherapy can improve the treatment efficacy of metastatic melanoma. This
      study was to investigate hepatic intra-arterial bio-chemotherapy for the
      treatment and survival of patients with liver metastasis from melanoma. METHODS:
      Twenty-one patients with liver metastasis from melanoma were treated with hepatic
      intra-arterial infusion of dacarbazine (250 mg/m(2)) from the first to the fifth
      day, and fotemustine (100 mg/m(2)) at the sixth and fourteenth day, followed by
      adoptive transfer of autologous cytokine-induced killer cells and administration
      of interleukin-2 and 150 ug granulocyte/macrophage colony stimulating factor for
      10-12 days. The treatment was repeated every 28 days. The overall survival,
      response and toxicity were analyzed. RESULTS: Seventeen of twenty-one patients
      were evaluable. One achieved complete remission (CR), one achieved partial
      remission (PR), six had stable disease (SD) and nine had progression disease
      (PD).The disease control rate was 47.06% (8/17), with a median progression free
      survival (PFS) of 3.76 months and a medium overall survival (OS) of 6 months.
      Treatment related complications were mainly myelosuppression (grade III-IV),
      occurring in 38.1% (8/21) patients. CONCLUSIONS: Hepatic intra-arterial
      chemotherapy can improve the disease control rate of progressive melanoma. It
      tends to prolong the PFS and OS with tolerable toxicity in patients with liver
      metastasis from melanoma.

PMID- 18710620
TI  - [Tracheal stent implantation for the treatment of tumor-induced acute airway
      stenosis].
AB  - BACKGROUND & OBJECTIVE: Tumor-induced acute airway stenosis is a medical
      emergency. Metal airway stent implantation can relieve dyspnea of patients
      suffering from this symptom and provide time for their further treatment. This
      study was to investigate the clinical application, efficacy, and complication
      management of tracheal stent implantation for the treatment of tumor-induced
      acute airway stenosis. METHODS: Nickel-titanium (Ni-Ti) alloy stent implantation
      was performed under the guidance of fiber-optic bronchoscopy in 52 patients with
      tumor-induced acute airway stenosis. RESULTS: Stent implantation was successful
      in all 52 patients. Dyspnea in all patients was significantly relieved. Values of
      arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon
      dioxide (PaCO2), and Karnofsky performance status (KPS) changed from (7.74+/
      0.99) kPa, (5.37+/-0.39) kPa, and (68.85+/-8.08) preoperatively to (11.12+/-0.61)
      kPa, (4.58+/-0.30) kPa, and (84.62+/-5.03) postoperatively (P<0.01). The three
      year survival rate was higher in lymphoma group than in lung cancer or esophageal
      cancer group. Postoperative complications were properly managed in all cases
      after symptomatic treatments. CONCLUSIONS: Tracheal stent implantation is an
      effective palliative treatment for acute dyspnea caused by local tumor
      compression or tumor invasion of large airways. It can rescue patients at risk
      for airway obstruction, improve the quality of life in terminal cancer patients,
      and provide further treatment opportunities for them.

PMID- 18710621
TI  - [Correlation of MRI features to histopathologic grade of soft tissue sarcoma].
AB  - BACKGROUND & OBJECTIVE: Peripheral tumor growth pattern plays an important role
      in the local recurrence and metastases of soft tissue sarcoma. This study was to
      determine the peripheral growth pattern of soft tissue sarcoma by magnetic
      resonance imaging (MRI), explore its correlation to histological grade, and
      assess biological features of soft tissue sarcoma before operation. METHODS: MRI
      was performed in 59 patients with soft tissue sarcoma. T1- and T2-weighted images
      were obtained using a spin-echo (SE) pulse sequence. Tumor margin, peritumoral
      high signal intensity sign and peritumoral low signal intensity capsule-like sign
      were evaluated on MR images. All patients were confirmed and graded by
      histopathology. RESULTS: The histological grade of soft tissue sarcoma was
      closely related to the margin appearance (P<0.05): the margin was well defined in
      60.0% grade I tumors, and poorly defined in 60.0% grade III tumors. No
      significant difference in the occurrence rates of peritumoral high signal
      intensity sign and peritumoral low signal intensity capsule-like sign was found
      between grade II and grade III tumors (P>0.05). The occurrence rate of
      peritumoral high signal intensity sign was significant lower and that of
      peritumoral low signal intensity capsule-like sign was significant higher in
      grade I tumors than in grade II-III tumors (10.0% vs. 74.4%, 80.0% vs. 15.4%,
      P<0.05). CONCLUSION: The peripheral tumor growth pattern is related with
      histological grade, and may reflect the biological behaviors of soft tissue
      sarcoma.

PMID- 18710622
TI  - [Diagnosis and therapeutics of 24 cases of pulmonary sclerosing hemangioma].
AB  - BACKGROUND & OBJECTIVE: Pulmonary sclerosing hemangioma (PSH) is an uncommon
      benign lung tumor. The study was to investigate the clinical features, diagnosis,
      treatment, and prognosis of PSH in order to promote the recognition of this
      disease. METHODS: Data of 24 pathologically confirmed PSH patients treated in Sun
      Yat-sen University Cancer Center from Jan. 1999 to Jul. 2007 were reviewed. The
      clinical features, diagnosis, treatment, and prognosis were summarized. RESULTS:
      Of the 24 patients, two (8.3%) were males, and 22 (91.7%) were females. The
      median age of the patients was 54.5 years old, ranging from 21 to 76 years old.
      Ten (41.7%) patients were detected upon routine medical examination, while 14
      (58.3%) patients presented clinical symptoms, including cough, hemoptysis, chest
      pain, chest distress and tachypnea. The imaging examination revealed isolated
      round or similar round nodules with distinct margins and homogeneous density. No
      calcification and aerial semilunar sign appeared. All the patients received
      surgical resection without complications and mortality. Eight patients underwent
      lobectomy, 13 underwent wedge resection, two underwent tumor resection and one
      underwent segmentectomy. There was no recurrence or metastasis during follow-ups.
      CONCLUSIONS: Clinical and radiological characteristics of PSH are nonspecific.
      Thus, accurate diagnosis of PSH before operation is difficult. Confirmation of
      PSH depends on pathological examination. Surgical resection is an effective
      treatment for PSH, among which lobectomy or limited resection is advisable, while
      systematic lymph node dissection is not recommended.

PMID- 18710623
TI  - [Occurrence and influencing factors of paranasal sinusitis in nasopharyngeal
      carcinoma patients after radiotherapy].
AB  - BACKGROUND & OBJECTIVE: Radiation usually results in paranasal sinusitis in
      nasopharyngeal carcinoma (NPC) patients, which influences patients' quality of
      life. This study was to explore the occurrence and influencing factors of
      paranasal sinusitis in NPC patients before and after radiotherapy. METHODS:
      Clinical data of 381 NPC patients, treated in Cancer Center of Sun Yat-sen
      University from Jan. 1998 to Jul. 2000, were reviewed. CT images before and after
      radiotherapy were compared. The occurrence and influencing factors of paranasal
      sinusitis were analyzed. RESULTS: Of the 381 NPC patients, 176 (46.2%) suffered
      from paranasal sinusitis before radiotherapy. Among the 205 NPC patients without
      paranasal sinusitis before radiotherapy, 103 (50.2%) developed paranasal
      sinusitis after radiotherapy; the occurrence rates of paranasal sinusitis at 1
      month, 3 months, 6 months, and 1 year after radiotherapy were 21.0%, 33.7%, 41.5%
      and 29.3%, respectively (Chi(2)=20.92, P<0.001). Logistic analysis showed that T
      stage was related to the occurrence rate of paranasal sinusitis. CONCLUSION: The
      incidence of paranasal sinusitis in NPC patients after radiotherapy is high and
      related to T stage.

PMID- 18710624
TI  - [Effects of the lung protective ventilatory strategy on proinflammatory cytokine
      release during one-lung ventilation].
AB  - BACKGROUND & OBJECTIVE: A prolonged period of one-lung ventilation(OLV) is
      required during thoracic surgery and this may activate cytokine release and cause
      lung inflammatory response. The lung protective ventilatory strategy has reduced
      lung and systemic cytokine release and achieved remarkable curative effect in
      patients with acute respiratory distress syndrome (ARDS). This study was to
      investigate the effect of the lung protective ventilatory strategy on
      proinflammatory cytokine release during OLV in patients underwent thoracic
      surgery. METHODS: Forty patients underwent esophagectomy were randomly divided
      into conventional ventilation (CV) group (n=20) and protective ventilation (PV)
      group (n=20). In CV group, all patients received two-lung ventilation (TLV) and
      OLV with a tidal volume (VT) of 10 mL/kg and an inspiration/expiration ratio
      (I/E) of 1:1.5. In PV group, all patients received TLV with a VT of 10 mL/kg and
      an I/E ratio of 1:1.5, and received OLV with a VT of 5-6 mL/kg and an I/E ratio
      of 1:1, along with positive end-expiratory pressure (PEEP) preset at 3-5 cm H2O.
      Blood samples of 3 mL were extracted at three time courses, which were after
      tracheal intubation (T1), 120 min after OLV (T2) and 24 h after operation (T3),
      to analyze concentrations of interleukin (IL)-6 and IL-8 in the two groups.
      Values of airway peak pressure (Ppeak), airway plateau pressure (Pplat), and
      airway resistance(Raw)were also recorded using side stream spirometry. RESULTS:
      In CV group, concentrations of IL-6 and IL-8 at T2 [(269.4+/-57.2) ng/L, (180.8+/
      35.0) ng/L] and T3[(335.8+/-98.7) ng/L,(178.5+/-18.3) ng/L] were significantly
      increased as compared with those at T1 [(17.0+/-5.4) ng/L,(18.2+/-2.8)
      ng/L](P<0.05). In PV group, concentrations of IL-6 and IL-8 at T2 [(209.3+/-55.7)
      ng/L], (115.3+/-71.5) ng/L] and T3 [(278.2+/-100.8) ng/L,(124.2+/-40.1) ng/L]
      were significantly increased as compared with those at T1[(20.0+/-7.1)
      ng/L,(15.3+/-3.6) ng/L] (P<0.05). Concentrations of IL-6 and IL-8 at T2 and T3
      were significantly higher in CV group than in PV group (P<0.05). Ppeak, Pplat and
      Raw at T2 were significantly higher in CV group [(33.6+/-4.6 cmH2O,(21.5+/-3.1)
      cmH2O, (26.3+/-2.1) cmH2O.L(-1).S(-1)] than in PV group [(26.7+/-3.5) cmH2O,
      (12.4+/-2.1) cmH2O, (18.3+/-2.3) cmH2O.L(-1).S(-1)](P<0.05). CONCLUSIONS:
      Concentrations of IL-6 and IL-8 are increased during and after OLV in thoracic
      surgery. The lung protective ventilatory strategy can reduce the airway pressure
      and airway resistance during OLV, decrease the release of IL-6 and IL-8, and
      inhibit lung inflammatory responses during OLV and postoperatively.

PMID- 18710625
TI  - [Expression and clinical significance of a disintegrin and metalloprotease 8
      (ADAM8) and epidermal growth factor receptor (EGFR) in non-small cell lung
      cancer].
AB  - BACKGROUND & OBJECTIVE: Up-regulation of a disintegrin and metalloprotease 8
      (ADAM8) is correlated with genesis, progression, invasion, and metastasis of
      tumors. However, the expression of ADAM8, especially its correlation to epidermal
      growth factor receptor (EGFR), has seldom been reported in non-small cell lung
      cancer (NSCLC). This study was to investigate expressions of ADAM8 and EGFR in
      NSCLC, and to analyze their correlations. METHODS: Expressions of ADAM8 and EGFR
      in 49 specimens of NSCLC, 28 specimens of adjacent lung tissues and 13 specimens
      of benign lung tissues were detected using tissue microarray (TMA) and
      immunohistochemistry (IHC). The interrelationship between the two factors and
      their correlations to clinicopathologic features of NSCLC were analyzed. RESULTS:
      ADAM8 and EGFR were mainly expressed in the cytoplasm and on the cell membrane.
      The positive rates of ADAM8 and EGFR were significantly higher in NSCLC than in
      adjacent lung tissues and benign lung tissues (73.5% vs. 10.7% and 15.4%, 69.4%
      vs. 14.2% and 23.1%, P<0.01). The positive rates of ADAM8 and EGFR were slightly
      lower in squamous cell carcinoma than in adenocarcinoma (73.1% vs. 80.0%, 65.4%
      vs. 75.0%, P>0.05), while were significantly higher in stage N1-N3 NSCLC than in
      stage N0 (85.7% vs. 42.8%, 82.8 vs. 35.7%, P<0.01) and significantly higher in
      stage III-IV NSCLC than in stage I-II (90.0% vs. 62.1%, 90.0% vs. 65.5%, P<0.05).
      The expression of ADAM8 was positively correlated to EGFR (r=0.589, P<0.01), with
      a kappa value of 0.522. CONCLUSION: ADAM8 and EGFR are overexpressed in NSCLC,
      and their expressions are consistent.

PMID- 18710626
TI  - [Correlation of fever to infection in patients with chemotherapy-induced
      neutropenia].
AB  - BACKGROUND & OBJECTIVE: The cancer patients with chemotherapy-induced neutropenia
      often suffer from fever and infection, but current opinions on the correlation of
      the fever to infection are controversial. This study aimed to investigate the
      incidence and correlation of fever and infection in cancer patients with
      chemotherapy-induced neutropenia. METHODS: Clinical data of 256 in-patients with
      chemotherapy-induced neutropenia from Jan. to Jul. 2007 were analyzed. The
      occurrence of fever and infection in these patients were analyzed by using
      descriptive analysis and agreement test. RESULTS: Of the 256 patients, 100
      (39.1%) suffered from fever, and 42 (16.4%) experienced infection. The
      temperature of febrile patients was (39.0+/-0.64)celsius. The main sites of
      infection were the pharynx (42.9%), oral cavity (21.4%) and low respiratory tract
      (14.3%). The consistency rate was 0.75 between fever and infection (Kappa=0.414,
      P<0.001). CONCLUSION: The incidence of fever and infection in cancer patients
      with chemotherapy-induced neutropenia are high with a moderate agreement between
      fever and infection.

PMID- 18710627
TI  - [Can defective TGF-Beta signaling be an Achilles heel in human cancer?].
AB  - Survival signals in cancer cells activate mTOR-the mammalian target of rapamycin.
      mTOR suppresses TGF-beta signals that arrest cell cycle progression in late G1
      thus activated mTOR prevents cell cycle arrest at a checkpoint mediated by TGF
      beta. Rapamycin treatment resurrects TGF-beta signals causing G1 arrest. Defects
      in TGF-beta signaling are common in human cancer, and ironically, cancer cells
      with defective TGF-beta signaling that do not arrest in G1, instead undergo
      apoptosis when treated with rapamycin. Thus, defective TGF-beta signaling may
      represent an Achilles heel for rational therapeutic targeting of cancer cells
      using rapamycin-based strategies.

PMID- 18710628
TI  - [Recent developments in radiation oncology-integrating radiation physics and
      molecular radiobiology advances into clinical radiotherapy practice and beyond].
AB  - Significant developments in radiation oncology have taken place in recent years
      as a result of advances in radiation physics and molecular radiobiology. From the
      conventional 2-dimensional (2D) radiotherapy to 3-dimensional (3D) conformal
      radiotherapy, we have now entered the era of intensity-modulated radiotherapy
      (IMRT) and image-guided radiotherapy (IGRT). IMRT/IGRT allows conformal treatment
      of tumor and conformal avoidance of normal tissues leading to possible
      improvement of tumor control and decrease in treatment-related toxicity.
      Frameless stereotactic radiosurgery (SRS) and stereotactic body radiotherapy
      (SBRT) have now become a reality, offering more treatment options in radiation
      oncology. With technological advances in image guidance, brachytherapy especially
      in early stage prostate cancer has progressed and shown excellent long-term
      outcome data. Charged particle therapy including proton therapy is a promising
      area for new development. Combining radiotherapy with the more traditional
      chemotherapy and hormonal therapy to novel targeted therapy and gene therapy is
      aimed to overcome radio-resistance, improve the radio-therapeutic index and
      provide better loco-regional and systemic control of cancer. A recent randomized
      trial in head and neck cancer has shown improved survival data when comparing
      combined radiotherapy and targeted therapy with radiotherapy alone. Recent
      advances in functional or molecular imaging offer new opportunity to improve
      targeting of tumor, for example, hypoxic region, and possibly to perform
      radiation dose painting with IMRT. Integrating PET/CT in radiotherapy has shown
      promise in assisting target delineation during treatment planning and assessing
      radiation treatment response. Cancer stem cell, gene expression profiling and
      nanotechnology with the implications on radio-resistance are new exciting areas
      requiring more research in future as we move toward personalized medicine.

PMID- 18710629
TI  - [Significance of Forkhead Box m1b (Foxm1b) gene in cell proliferation and
      carcinogenesis].
AB  - Forkhead Box m1b (Foxm1b) is a subtype of the Fox transcription factor family. It
      is detected in all proliferative cells, but disappears when cells enter into
      their terminal differentiation phase. Foxm1b is closely related to hepatocellular
      growth, mainly through inhibiting cyclin-dependent kinase (CDK) inhibitors to
      influence cell proliferation. It also participates in growth hormone (GH)
      mediated cell multiplication, but does not induce tumors. The expression of
      Foxm1b has been observed in many tumor cell lines and malignant tumors,
      indicating that it might be an essential proto-oncogene in carcinogenesis.
      Furthermore, Foxm1b may take part in liver regeneration after hepatectomy,
      hepatic failure and liver transplantation. Foxm1b is a new potential target for
      the treatment human hepatic cell carcinoma (HCC).

PMID- 18710630
TI  - Effects of vibration therapy on bone mineral density in postmenopausal women with
      osteoporosis.
AB  - BACKGROUND: Jaw osteonecrosis possibly associated with the administration of
      bisphosphonates is expected to be treated with a non-pharmacologic approach. This
      study aimed to determine whether noninvasive, mechanically mediated vibration
      would inhibit the decline in bone mineral density (BMD) that follows menopause,
      enhance the BMD of the lumbar and femoral neck, and reduce chronic back pain in
      postmenopausal women with osteoporosis. METHODS: A total of 116 postmenopausal
      women with osteoporosis participated in this study, and they were divided into
      groups A (66 patients) and B (50). Group A received vibration treatment (Subjects
      vertically stand on the vibration platform, with a vibration frequency of 30 Hz,
      amplitude of 5 mm; they received the treatment five times per week, ten minutes
      each time and totally for six months), whereas women of group B served as
      controls without any treatment. L2 - 4 BMD, bilateral femoral neck BMD, and body
      mass index (BMI) were recorded before the treatment or at the third and sixth
      months of the treatment respectively. After the ending of the treatment, the
      change of BMD in each group was compared and analyzed. Chronic back pain was
      evaluated by visual analogue scale (VAS) at baseline and the third and sixth
      months of the treatment. RESULTS: Of the 116 women, 94 including 51 women from
      group A ((61.23 +/- 8.20) years) and 43 women from group B ((63.73 +/- 5.45)
      years), completed the study. There were no significant differences in baseline
      characteristics including age, BMI, menopausal years, lumbar BMD, femoral neck
      BMD, and VAS between the two groups. The lumbar BMD of the 51 women in group A
      increased by 1.3% (P = 0.034) after vibration treatment for 3 months and by 4.3%
      at the sixth month (P = 0.000). The lumbar BMD in group B was decreased at the
      third month, but there was not statistical significance (P > 0.05). At the sixth
      month, it was decreased by 1.9% (P < 0.05). The femoral neck BMD of the 51 women
      in group A was slightly increased after vibration treatment for 3 months, but
      without statistical significance (P > 0.05). At the sixth month, the BMD was
      increased by 3.2% (P < 0.05). In group B, the BMD was not decreased significantly
      (P = 0.185) at the third month, but decreased significantly at the sixth month
      (1.7%) (P < 0.05) compared with the baseline. Chronic back pain (VAS) reduced
      more significantly in group A at the third and the sixth months (P < 0.05) after
      vibration therapy in comparison with the baseline. The BMI was not significantly
      changed in the two groups during the period of follow-up. CONCLUSIONS: Vibration
      therapy appears to be useful in reducing chronic back pain and increasing the
      femoral neck and lumbar BMD in postmenopausal women with osteoporosis.

PMID- 18710631
TI  - Multicenter clinical study on the efficacy and safety of inhalable insulin
      aerosol in the treatment of type 2 diabetes.
AB  - BACKGROUND: A new inhalable insulin aerosol (Inh-Ins) was developed in China. The
      aim of this multicenter clinical study was to evaluate the efficacy and safety of
      this new Inh-Ins as a treatment of type 2 diabetes. Regular porcine insulin (RI)
      was used as a control. METHODS: This study is a prospective, randomized, open
      label, parallel-group multicenter clinical trial in which 253 qualified patients
      with type 2 diabetes received the insulin Glargine daily at bedtime plus either a
      pre-meal Inh-Ins or a pre-meal subcutaneous RI for 12 weeks. HbA1c, fasting
      plasma glucose (FPG), the 1-hour-postprandial blood glucose (1hPBG) and the 2
      hour-postprandial blood glucose (2hPBG) were measured. Events were monitored for
      adverse effects. RESULTS: After 12 weeks, the HbA1c decreased significantly from
      baseline in both treatment groups, with no significant difference between the two
      regimens. In the Inh-Ins group, FPG, both 1hPBG and 2hPBG significantly declined
      from baseline after the 8th- and 12th-weeks of treatment. The reduced values of
      FPG or 1hPBG between the two groups showed a more significant hypoglycemic effect
      with the Inh-Ins than the RI. After 12 weeks, the pulmonary carbon monoxide
      diffusing capacity (DLco) was significantly lower in Inh-Ins group than in the
      RI. The main side effects of Inh-Ins were coughing, excessive sputum, and
      hypoglycemia. CONCLUSIONS: Inh-Ins was effective in decreasing HbA1c like the RI.
      It was better in lowering the FPG and the 1hPBG than the RI. Its main side
      effects were coughing, excessive sputum, and hypoglycemia. Also, Inh-Ins slightly
      impaired DLco.

PMID- 18710632
TI  - Association of SelS mRNA expression in omental adipose tissue with Homa-IR and
      serum amyloid A in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Tanis was reported as a putative receptor for serum amyloid A (SAA)
      involving glucose regulated protein in insulin regulated resistance. It was found
      to be dysregulated in diabetic rats (Psammomys obesus, Israeli sand rat) and its
      homologue for humans is SelS/AD-015. The present study analyzed mRNA expression
      of SelS in omental adipose tissue biopsies from patients with type 2 diabetes
      mellitus (T2DM), and age- and weight-matched nondiabetic patients, the
      relationship of SelS mRNA with Homa-IR and serum SAA level. METHODS: Human
      omental adipose tissues from ten cases of type 2 diabetic patients and twelve
      cases of nondiabetic individuals were analyzed for the expression level of SelS
      mRNA by semiquantitative polymerase chain reaction (PCR), Homa-IR estimated by
      standard formula and SAA level by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: SelS mRNA expression, Homa-IR and serum SAA were higher in T2DM
      sufferers than in nondiabetic control group. SelS mRNA level was positively
      correlated with Homa-IR and SAA level in each group. CONCLUSIONS: SelS protein
      may be involved in insulin resistance in Chinese with T2DM by acting as the SAA
      receptor, thus playing an important role in the development of T2DM and
      atherosclerosis.

PMID- 18710633
TI  - Complications associated with the apnea test in the determination of the brain
      death.
AB  - BACKGROUND: An apnea test is essential in the clinical determination of brain
      death. This study was conducted to analyse complications associated with the
      apnea test in the determination of the brain death. METHODS: On 93 adult patients
      in coma in Zhejiang Province of China from January 2003 to December 2006, 179
      apnea tests were performed as a part of the determination of brain death.
      Potential risk conditions and complications were analysed during apnea tests.
      RESULTS: During apnea, serious cardiac arrhythmia did not occur in all patients.
      Complications occurred in 37 of 179 (21%) apnea tests. Hypotension occurred in 30
      patients (17%) and it was observed in 8/94 (9%) tests with baseline value of
      systolic arterial blood pressure not less than 120 mmHg, and 22/85 (26%) less
      than 120 mmHg (P < 0.05). Severe hypoxaemia occurred in 10 patients (6%) of which
      3/138 (2%) tests with baseline value of arterial oxygen pressure not less than
      200 mmHg, and 7/41 (17%) less than 200 mmHg (P < 0.05). CONCLUSIONS: This study
      demonstrated that complications occurred mostly in patients with inadequate
      baseline systolic arterial blood pressure and preoxygenation. Adequate
      precautions during the apnea tests may reduce the risk of cardiovascular and
      oxygenation complication.

PMID- 18710634
TI  - Prostaglandin induces the expression of matrix metalloproteinase-1 in ciliary
      melanocytes.
AB  - BACKGROUND: Latanoprost, a prostaglandin F2alpha analog, has been shown to be an
      effective intraocular pressure lowering agent which acts by inducing ciliary
      muscle cells to synthesise matrix metalloproteinases. However, the response of
      ciliary melanocytes to latanoprost has never been reported. This research has
      investigated the ability of latanoprost to induce matrix metalloproteinase-1
      expression in human ciliary melanocytes, and thereby advance the understanding of
      the mechanism of PGF(2alpha) in decreasing intraocular pressure. METHODS: In
      vitro human ciliary melanocytes were treated for 48 hours with five different
      concentrations of latanoprost (100, 150, 200, 500, and 1000 nmol/L). Ciliary
      melanocytes treated with 0.01% ethanol (vehicle) were used as a control. The
      expression of matrix metalloproteinase-1 in ciliary melanocytes was determined by
      Western blotting and immunofluorescent staining. RESULTS: Western blotting showed
      that the expression of matrix metalloproteinase-1 in ciliary melanocytes was
      induced by latanoprost, and the level of expression was dependent on the
      concentration of latanoprost in the culture medium. Immunofluorescent staining
      showed that matrix metalloproteinase-1 was confined to the ciliary melanocyte
      cytoplasm. CONCLUSIONS: Latanoprost induced the expression of matrix
      metalloproteinase-1 in human ciliary melanocytes in a dose-dependent manner.
      Ciliary melanocytes, as well as ciliary muscle cells, may also play an important
      role in uveoscleral outflow modulation.

PMID- 18710635
TI  - Altered surfactant protein A gene expression and protein homeostasis in rats with
      emphysematous changes.
AB  - BACKGROUND: The decrease of surfactant protein (SP) secreted by the alveolar type
      II cell is one of the important causes of limiting air of pulmonary emphysema.
      However, the SP-A gene and protein changes in this disease are rarely studied.
      This study was undertaken to investigate alterations in SP-A gene activity and
      protein, and to explore their roles in the pathogenesis of emphysematous changes.
      METHODS: Twenty Wistar rats were divided randomly into a normal control group (n
      = 10) and a cigarette smoking (CS) + lipopolysaccharide (LPS) group (n = 10).
      Ultra-structural changes were observed under an electron microscope. The number
      of cells positive for SP-A was measured by immunohistochemistry. The mRNA
      expression and protein level of SP-A in the lung tissues were determined by
      quantitative polymerase chain reaction (qPCR) and Western blot separately. The
      protein level of SP-A in lavage fluid was determined by Western blot. RESULTS:
      The number of cells positive for SP-A of the CS + LPS group (0.35 +/- 0.03) was
      lower than that of the blank control group (0.72 +/- 0.06, P < 0.05). The level
      of SP-A in the lung tissues of rats in the CS + LPS group (0.2765 +/- 0.0890) was
      lower than that in the blank control group (0.6875 +/- 0.1578, P < 0.05). The
      level of SP-A in the lavage fluid of rats in the CS + LPS group (0.8567 +/-
      0.1458) was lower than that in the blank control group (1.3541 +/- 0.2475, P <
      0.05). The lung tissues of rats in the CS + LPS group showed an approximate
      increase (0.4-fold) in SP-A mRNA levels relative to beta-actin mRNA (P < 0.05).
      CONCLUSIONS: The changes of SP-A may be related to emphysematous changes in the
      lung. And cigarette smoke and LPS alter lung SP-A gene activity and protein
      homeostasis.

PMID- 18710636
TI  - Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on
      gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in
      vitro.
AB  - BACKGROUND: Diabetic gastroparesis is a disabling condition with no consistently
      effective treatment. In normal animals, both ghrelin and its synthetic peptide,
      growth hormone releasing peptide 6 (GHRP-6), increase gastric emptying. Thus, we
      investigated the potential therapeutic significance of ghrelin and GHRP-6 in
      diabetic guinea pigs with gastric motility disorders. METHODS: A diabetic guinea
      pig model was produced by intraperitoneal (i.p.) injection of streptozotocin
      (STZ, 280 mg/kg). Diabetic guinea pigs were injected i.p. with ghrelin or GHRP-6
      (10 - 100 microg/kg), and the effects on gastric emptying were measured after
      intragastric application of phenol red. The effect of atropine or a growth
      hormone secretagogue receptor (GHS-R) antagonist, D-Lys(3)-GHRP-6, on the
      gastroprokinetic effects of ghrelin or GHRP-6 (100 microg/kg) was also
      investigated. Further, the in vitro effects of ghrelin or GHRP-6 (0.01 - 10
      micromol/L) on spontaneous or carbachol-induced contractile amplitude in gastric
      fundic circular strips taken from diabetic guinea pigs were examined. Growth
      hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea
      pigs were detected by reverse transcriptase polymerase chain reaction (RT-PCR).
      RESULTS: We established a guinea pig model of delayed gastric emptying. Ghrelin
      (20, 50, or 100 microg/kg) and GHRP-6 (20, 50, or 100 microg/kg) accelerated
      gastric emptying in diabetic guinea pigs with gastroparesis (n = 6, P < 0.05). In
      the presence of atropine, which delayed gastric emptying, ghrelin and GHRP-6 (100
      microg/kg) failed to accelerate gastric emptying (n = 6, P < 0.05). D-Lys(3)-GHRP
      6 also delayed gastric emptying induced by the GHS-R agonist (n = 6, P < 0.05).
      Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in
      gastric fundic strips taken from diabetic guinea pigs (n = 6, P < 0.05). RT-PCR
      confirmed the presence of GHS-R mRNA in the strip preparations. CONCLUSIONS:
      Ghrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with
      gastroparesis, potentially, by activating the peripheral cholinergic pathways in
      the enteric nervous system.

PMID- 18710637
TI  - Effects of delayed brain-derived neurotrophic factor application on cochlear
      pathology and auditory physiology in rats.
AB  - BACKGROUND: The development and maintenance of spiral ganglion cells (SGCs)
      appear to be supported by neurotrophins. Removal of this support leads to their
      gradual degeneration. Intracochlear infusion with neurotrophins can provide
      trophic support to SGCs in animal deafness models if given shortly after
      deafening. However, it is not known whether delayed intervention will provide
      similar protection, which might be clinically relevant. The present research was
      conducted to determine the effects of brain-derived neurotrophic factor (BDNF)
      administration on the capacity of the peripheral processes to resprout. METHODS:
      The left cochlea of 20 profoundly deafened rats, which were divided into 2 groups
      equally, was implanted with an electrode and drug-delivery system 30 days after
      deafening. Either BDNF or artificial perilymph (AP) was delivered continuously
      for 28 days. Electrically evoked auditory brainstem responses (EABRs) were
      recorded during the period. SGC body and peripheral process density were
      measured. RESULTS: The EABR thresholds of AP increase continually. Those of BDNF
      increase slowly at the beginning then decrease, and were significantly less than
      those of the AP group from day 14 to 28 (P < 0.01). In terms of SGC and
      peripheral process density, the difference between the treated and control ears
      of BDNF group was clearly significant (P < 0.01), but not in AP group (P > 0.05).
      Analysis of the left cochlea between the two groups demonstrated that
      SGC/peripheral process density of the BDNF group was significantly greater than
      that of the AP group. Finally, a functional formula was developed relating the
      last EABR threshold and SGC density and process density, which was as follows: T
      = 466.184 - 2.71 (F.B.L). CONCLUSIONS: Under the conditions of delayed
      intervention following 30 days after deafening in rats, it can be concluded that
      BDNF enhances SGC bodies and peripheral processes survival after differentiation
      and so improves auditory sensitivity. SGC peripheral processes influence the
      auditory sensitivity.

PMID- 18710638
TI  - Biochemical pathways in the antiatherosclerotic effect of berberine.
AB  - BACKGROUND: This study investigated the inhibitory effect of berberine (BBR) on
      lipopolysaccharide (LPS) induced cyclooxygenase-2 (COX-2) expression via the
      mitogen activated protein kinase (MAPK) signalling cascade pathways in human
      peripheral blood monocytes (PBMC). METHODS: PBMC from whole blood were isolated
      and cultured for up to 24 hours after division into 5 groups treated with LPS,
      LPS + BBR 25 micromol/L, LPS + BBR 50 micromol/L or LPS + BBR 100 micromol/L and
      untreated. Monocytes were extracted for RT-PCR and Western blot analyses to
      examine COX-2 mRNA and protein activated expression of p38 mitogen activated
      protein kinase (p38MAPK), Jun N-terminal kinase (JNK) and extracellular regulated
      kinases 1/2 (ERK1/2) signalling pathways. RESULTS: COX-2 mRNA and protein
      expression decreased to a minimum at 12 hours after BBR treatment (P < 0.05).
      With the increasing concentration of BBR treatment, the COX-2 expression
      decreased progressively (P < 0.01). With BBR treatment for 6, 12 or 24 hours at
      three doses, ERK1/2 protein expression was significantly inhibited. For the JNK
      pathway, only with the treatment of BBR at the concentration of 100 micromol/L
      was JNK protein expression inhibited compared with the LPS stimulation group (P <
      0.01). Irrespective of the BBR concentration, no difference was shown between the
      BBR group and the LPS group for p38MAPK protein expression. Human monocytes COX-2
      mRNA, by RT-PCR, and protein expression, by Western blot analysis, were inhibited
      when incubated with PD98059, SP600125 and SB203580 (P < 0.05). CONCLUSIONS:
      Berberine inhibits COX-2 expression via the ERK1/2 signalling pathway and,
      possibly, at a high dosage via the JNK pathway. P38MAPK may have no relationship
      with the effect of BBR in PBMC. Berberine inhibited COX-2 mRNA and protein
      expression in a dose dependent manner and suppressed COX-2 expression to a
      minimal level after 12 hours of berberine treatment.

PMID- 18710639
TI  - Resveratrol reestablishes spermatogenesis after testicular injury in rats caused
      by 2, 5-hexanedione.
AB  - BACKGROUND: Environmental toxins can destroy the physiological process of
      spermatogenesis and even lead to male infertility. Resveratrol (RES) is a natural
      phytoalexin with a wide range of biological activities. Some recent researches
      have demonstrated that RES can increase sperm output and protect sperm from
      apoptosis caused by physical damage. However, there is no evidence indicating
      that it can also exhibit a similar activity in testis injury caused by
      environmental toxins. This study was designed to evaluate the protective effect
      of resveratrol on testis damaged by environmental toxins and to elucidate the
      possible mechanism of its protective effect. METHODS: In this study 2, 5
      hexanedione (2, 5-HD) was used as the injury agent. Forty male SD rats were
      randomly divided into 5 groups. During the first 5 weeks, group A was raised
      normally, groups B, C, D and E were exposed to 1% 2, 5-HD; during the following 9
      weeks, group C, D, E received intragastric administration of different
      concentrations of resveratrol (20 mg x kg(-1) x d(-1), 40 mg x kg(-1) x d(-1) and
      80 mg x kg(-1) x d(-1)), while groups A and B were treated by
      carboxymethylcellulose. Physical signs, body weight gain and testis weight were
      comparatively observed. Numbers and diameters of seminiferous tubules were
      analyzed following HE staining. In addition, expression of the c-kit protein and
      gene in spermatogenic cells in every group was detected with
      immunohistochemistry, Western blot or RT-PCR. RESULTS: The 2, 5-HD treatment
      resulted in physical signs that became worse and in emarciated testis. HE
      staining and immunohistochemistry showed that seminiferous tubules became
      emarcid, obsolete spermatogonia being stagnant and expression of c-kit protein
      being depressed. After oral administration of resveratrol, the 2, 5-HD-induced
      physical signs were improved and close to the normal rats. The gain of body
      weight increased (P < 0.01). The recovery of testis weight was significant (P <
      0.01). At the histological level, the seminiferous epithelia began to
      differentiate (P < 0.01); and even the physiological process of spermatogenesis
      restarted. Moreover, expression of c-kit protein and gene function resumed,
      although its expression remained different from the normal group. The diameter of
      and number of seminiferous tubules and the expression level of c-kit protein and
      gene activity were much closer to the normal group with increased doses of the
      resveratrol through oral administration. CONCLUSIONS: Resveratrol could
      ameliorate markedly the dyszoospermia induced by 2, 5-HD and induce
      spermatogenesis. The expression of c-kit, which is a specific marker protein of
      spermatogenic cell membranes, could be regulated by resveratrol.

PMID- 18710640
TI  - Role of nitric oxide during early phase myocardial ischemic preconditioning in
      rats.
AB  - BACKGROUND: To date, there have been no reports on altered nitric oxide (NO)
      content in ischemia/reperfusion with regard to in vivo preconditioning
      procedures. These studies are important for understanding the mechanisms of NO
      during early myocardial ischemic preconditioning. The aim of the present study
      was to investigate the mechanisms of NO during early myocardial ischemic
      preconditioning by measuring levels of NO and cyclic guanosine monophosphate
      (cGMP), as well as activity of nitric oxide synthase (NOS) in
      ischemia/reperfusion with respect to preconditioning in rats. METHODS: Sixty-six
      female Sprague-Dawley rats were randomly divided into four groups: ischemic
      preconditioning group (IP), ischemia/reperfusion group (I/R), control group
      (CON), and preconditioning procedure group (PC). In the PC group, rats were
      further divided into PC1-, PC1 +, PC2-, PC2 +, PC3-, and PC3 + subgroups. Rats
      underwent left coronary artery occlusion and reperfusion, and subsequently, NOS
      activity and levels were assessed with spectrophotometric analysis. cGMP contents
      were measured with radioimmunoassay. RESULTS: The level of NO and cGMP, as well
      as the activity of NOS, were significantly higher in the IP group compared to the
      I/R and CON groups (P < 0.05). During preconditioning prior to prolonged
      ischemia, NO and cGMP levels varied markedly with ischemia and reperfusion. The
      levels of NO repeatedly increased when the heart was exposed to three episodes of
      5-minute ischemia, and were almost completely reversed during each reperfusion
      period. NO and cGMP levels were significantly different between the 5-minute
      period of ischemia and the same period of reperfusion during preconditioning.
      CONCLUSIONS: NO plays an important role during early phase myocardial ischemic
      preconditioning in rats. NO and cGMP could be triggers and mediators of early
      phase myocardial ischemic preconditioning. Altered NOS activity following
      ischemic stress could be the primary inducer of higher NO levels detected. NO and
      cGMP fluctuations might be the trigger for protection during early phase
      myocardial ischemic preconditioning.

PMID- 18710642
TI  - Rapid response to lipids profile and leukocyte gene expression after rosuvastatin
      administration in Chinese healthy volunteers.
AB  - BACKGROUND: Statins are potent lipid-lowering agents widely used in medical
      practice. There has been growing evidence suggesting the pleiotropic effects of
      statins in addition to the lipid-lowering effect. However, it is still unclear
      how rapidly the beneficial effects of statins occur. The transcriptome of
      peripheral blood cells can be used as a sensor to drug therapy. The purpose of
      the study was to investigate the acute effects of rosuvastatin both on lipids
      profile and gene expression of peripheral leukocytes following therapy with a
      single dose of rosuvastatin. METHODS: Thirty healthy Chinese male volunteers were
      enrolled. The serum lipids, high-sensitivity C-reactive protein, and plasma
      fibrinogen were determined before and 72 hours after administration of 20 mg of
      rosuvastatin. The differentially expressed genes of peripheral leukocytes after
      administration of rosuvastatin were screened using human oligonucleotide
      microarray gene expression chips. Then four of the differentially expressed genes
      including ATM, CASP8, IL8RB and S100B were verified by real-time polymerase chain
      reaction (PCR). RESULTS: Rosuvastatin decreased both serum total cholesterol and
      low-density lipoprotein cholesterol significantly 72 hours after administration
      of a single dose of 20 mg rosuvastatin. However, no significant changes occurred
      in blood high-density lipoprotein cholesterol, triglycerides, C-reactive protein
      and fibrinogen after the treatment. A total of 24 genes were differentially
      expressed after the treatment. They were involved in important cell biological
      processes such as cytokine-cytokine receptor interaction, apoptosis signaling,
      etc. CONCLUSIONS: Rosuvastatin rapidly modulates the serum lipids and affects the
      gene expression of peripheral leukocytes in healthy volunteers. This finding
      provides some new clues for further studies on its potential pleiotropic effects.

PMID- 18710643
TI  - Compensatory function of bradykinin B1 receptor in the inhibitory effect of
      captopril on cardiomyocyte hypertrophy and cardiac fibroblast proliferation in
      neonatal rats.
AB  - BACKGROUND: Bradykinin (BK) acts mainly on two receptor subtypes: B(1) and B(2),
      and activation of B(2) receptor mediates the most well-known cardioprotective
      effects of angiotensin converting enzyme inhibitors (ACEi), however, the role
      that B(1) receptor plays in ACEi has not been fully defined. We examined the role
      of B(1) receptor in the inhibitory effect of ACE inhibitor captopril on rat
      cardiomyocyte hypertrophy and cardiac fibroblast proliferation induced by
      angiotensin II (Ang II) and explored its possible mechanism. METHODS: Neonatal
      cardiomyocytes and cardiac fibroblasts (CFs) were randomly treated with Ang II,
      captopril, B(2) receptor antagonist (HOE-140) and B(1) receptor antagonist (des
      Arg(10), Leu(9)-kallidin) alone or in combination. Flow cytometry was used to
      evaluate cell cycle, size and protein content. Nitric oxide (NO) and
      intracellular cyclic guanosine monophosphate (cGMP) level were measured by
      colorimetry and radioimmunoassay. RESULTS: After the CFs and cardiomyocytes were
      incubated with 0.1 micromol/L Ang II for 48 hours, the percentage of CFs in the S
      stage, cardiomyocytes size and protein content significantly increased (both P <
      0.01 vs control), and these increases were inhibited by 10 micromol/L captopril.
      However, NO and cGMP levels were significantly higher than that with Ang II alone
      (both P < 0.01). 1 micromol/L HOE-140 or 0.1 micromol/L des-Arg(10), Leu(9)
      kallidin attenuated the effects of captopril, which was blunted further by
      blockade of both B(1) and B(2) receptors. CONCLUSIONS: Acting via B(2) receptor,
      BK contributes to the antihypertrophic and antiproliferative effects of captopril
      on cardiomyocytes and CFs. In the absence of B(2) receptor, B(1) receptor may act
      a compensatory mechanism for the B(2) receptor and contribute to the inhibition
      of cardiomyocyte hypertrophy and CFs proliferation by captopril. NO and cGMP play
      an important role in the effect of B(1) receptor.

PMID- 18710644
TI  - Analysis of anti-platelet aggregation components of Rhizoma Zingiberis using
      chicken thrombocyte extract and high performance liquid chromatography.
AB  - BACKGROUND: The conventional procedure for screening bioactive components from
      traditional Chinese medicine is time-consuming, expensive and low efficient.
      Therefore, some alternative strategies are needed urgently. A novel method for
      screening anti-platelet aggregation components from oleoresins was developed
      using chicken thrombocyte extract and high performance liquid chromatography.
      METHODS: The anti-platelet aggregation components of oleoresins were combined
      with receptors, channels and enzymes of chicken thrombocytes under physiological
      environment. Unbound substances were washed away and bound compounds were eluted
      using specific phosphate buffered solution (PBS). Compounds released from target
      sites were collected and analyzed by high performance liquid chromatography and
      LC-MS. The activity of three compounds which were screened from this model was
      confirmed using platelet aggregation pharmacology in vivo. RESULTS: There were
      four typical compounds that bound to the thrombocytes: 6-gingerol, 8-gingerol, 6
      shogaol and 10-gingerol, and all had shown anti-platelet aggregation activities.
      Eight-gingerol displayed the best anti-platelet aggregation effect. CONCLUSIONS:
      Chicken thrombocyte extract can be used to isolate chemicals that are ligands of
      the receptor or other bio-targets on the platelet. This may therefore be a simple
      and efficient method to screen for anti-platelet aggregation compounds from
      traditional Chinese medicine.

PMID- 18710645
TI  - HIV/AIDS epidemiology and prevention in China.
AB  - OBJECTIVE: To review HIV/AIDS epidemic history, current situation and prevention
      policy in China. Data sources Information included in this article was identified
      by searching PUBMED (1997 - 2006) online resources using the key terms
      "HIV/AIDS", "epidemic", "prevention", and "China". Study selection Original
      milestone articles and critical reviews written by major pioneer investigators of
      the field were selected. RESULTS: The key issues related to the HIV/AIDS epidemic
      situation in China and Chinese government prevention policy were summarized.
      HIV/AIDS epidemic groups and trends for HIV transmission were discussed.
      CONCLUSION: In January 2006, 650 000 people were estimated to be living with HIV
      in China. The overall HIV/AIDS epidemic is at a low level (0.05%) and
      concentrated in several at risk populations. However, the data show that new
      cases of HIV infection are growing every year and spreading from at risk
      populations to the general population. Premier WEN Jia-bao announced the "Four
      frees and one care" policy and the Chinese government has developed a series of
      programs with strong policy measures to stop the spread of HIV/AIDS in China.

PMID- 18710646
TI  - Is hepatitis B virus reactivation a risk factor in the development of
      posttransplant lymphoproliferative disorder following liver transplantation?

PMID- 18710647
TI  - A novel mutation in a patient with congenital coagulation factor XII deficiency.

PMID- 18710648
TI  - Successful unrelated cord blood transplantation in a girl with malignant
      infantile osteopetrosis.

PMID- 18710649
TI  - On multiple testing, validation of gene expression profiling, and translational
      research.

PMID- 18710650
TI  - Different spatial organizations of saccade related BOLD-activation in parietal
      and striate cortex.
AB  - Voluntary saccades performed in total darkness provide the opportunity to
      investigate the brain system active during saccades without confounding effects
      caused by the saccade induced shifts of the retinal image. Using this approach
      saccade related activation has been demonstrated not only in parietal but also in
      striate cortex. Currently no information is available about the reference frame
      in which this activation is represented in parietal and in striate cortex.
      However, knowledge about how the brain codes spatial information about saccades
      in the absence of visual input is potentially relevant to our understanding of
      visually guided behaviour. The present study combines functional magnetic
      resonance imaging (fMRI) with simultaneous electrooculogram-recordings to provide
      evidence that volitional saccades executed in total darkness are represented in a
      retinotopic reference frame in a parietal brain area, the putative homologue of
      human LIP, and in a head/body centred egocentric reference frame in human V1. The
      potential co-existence of retinotopic and egocentric space representations in the
      primary visual cortex indicates that V1 may be involved in visuo-motor
      integration.

PMID- 18710651
TI  - Impaired spatial learning related with decreased expression of calcium/calmodulin
      dependent protein kinase IIalpha and cAMP-response element binding protein in the
      pentylenetetrazol-kindled rats.
AB  - Although its effect on cognitive functions has been one of the hot topics in the
      present neuroscience research, the mechanism of epilepsy related cognitive
      impairment is not clearly revealed. Intracellular Ca(2+) plays an important role
      in regulating many cellular functions including learning and memory, this
      experiment was therefore conducted, in which, we observed the behaviors of
      chronic epileptic rats kindled by pentylenetetrazol (PTZ) through Morris water
      maze (MWM), examined the concentration of intracellular free calcium
      ([Ca(2+)](i)) with flow cytometry, and tested the expression of
      calcium/calmodulin-dependent protein kinase IIalpha (CaMKII(alpha)) and cAMP
      response element binding protein (CREB) in hippocampus of those rats using
      western blot and reverse transcription-polymerase chain reaction (RT-PCR). The
      results demonstrate impaired ability of spatial learning and memory, increased
      concentration of [Ca(2+)](i), decreased expression levels of total CaMKII(alpha),
      phosphorylated CaMKII(alpha) (P-CaMKII(alpha)) and phosphorylated CREB (P-CREB)
      and decreased levels of CaMKII(alpha) mRNA and CREB mRNA of the epileptic rats
      compared with the normal control rats. Moreover, Nimodipine, an inhibitor of
      voltage-dependent L-type Ca(2+) channels (VDCCs), reduced the Racine's stage,
      improved the ability of spatial learning and memory, reversed the effect of
      Ca(2+) influx and expression levels of CaMKII(alpha) and CREB of the epileptic
      rats. We concluded that Ca(2+) influx, CaMKII(alpha) and CREB expression levels
      in hippocampus of chronic epileptic rats may be related with their impaired
      spatial learning and memory.

PMID- 18710653
TI  - High dietary omega-6 fatty acids contribute to reduced docosahexaenoic acid in
      the developing brain and inhibit secondary neurite growth.
AB  - Docosahexaenoic acid (DHA, 22:6omega-3) is a major polyunsaturated fatty acid in
      the brain and is required in large amounts during development. Low levels of DHA
      in the brain are associated with functional deficits. The omega-3 fatty acids are
      essential nutrients and their metabolism and incorporation in developing brain
      depends on the composition of dietary fat. We assessed the importance of the
      intake of the omega-3 fatty acid, 18:3omega-3 and the balance with the omega-6
      fatty acid, 18:2omega-6, and the effects of dietary arachidonic acid (20:4omega
      6) and DHA in milk diets using the piglet as a model of early infant nutrition.
      Piglets were fed (% energy) 1.2% 18:2omega-6 and 0.05% 18:3omega-3 (deficient),
      10.7% 18:2omega-6 and 1.1% 18:3omega-3 (contemporary), 1.2% 18:2omega-6 and 1.1%
      18:3omega-3 (evolutionary), or the contemporary diet with 0.3% 20:4omega-6 and
      0.3% DHA (supplemented) from birth to 30 days of age. Our results show that a
      contemporary diet, high in 18:2omega-6 compromises DHA accretion and leads to
      increased 22:4omega-6 and 22:5omega-6 in the brain. However, an evolutionary
      diet, low in 18:2omega-6, supports high brain DHA. DHA supplementation
      effectively increased DHA, but not the intermediate omega-3 fatty acids,
      20:5omega-3 and 22:5omega-3. Using primary cultures of cortical neurons, we show
      that 22:5omega-6 is efficiently acylated and preferentially taken up over DHA.
      However, DHA, but not 22:5omega-6 supports growth of secondary neurites. Our
      results suggest the need to consider whether current high dietary omega-6 fatty
      acid intakes compromise brain DHA accretion and contribute to poor
      neurodevelopment.

PMID- 18710652
TI  - The neural substrates of probabilistic and intertemporal decision making.
AB  - Many important decisions involve outcomes that are either probabilistic or
      delayed. Based on similarities in decision preferences, models of decision making
      have postulated that the same psychological processes may underlie decisions
      involving probabilities (i.e., risky choice) and decisions involving delay (i.e.,
      intertemporal choice). Equivocal behavioral evidence has made this hypothesis
      difficult to evaluate. However, a combination of functional neuroimaging and
      behavioral data may allow identification of differences between these forms of
      decision making. Here, we used functional magnetic resonance imaging (fMRI) to
      examine brain activation in subjects making a series of choices between pairs of
      real monetary rewards that differed either in their relative risk or their
      relative delay. While both sorts of choices evoked activation in brain systems
      previously implicated in executive control, we observed clear distinctions
      between these forms of decision making. Notably, choices involving risk evoked
      greater activation in posterior parietal and lateral prefrontal cortices, whereas
      choices involving delay evoked greater activation in the posterior cingulate
      cortex and the striatum. Moreover, activation of regions associated with reward
      evaluation predicted choices of a more-risky option, whereas activation of
      control regions predicted choices of more-delayed or less-risky options. These
      results indicate that there are differences in the patterns of brain activation
      evoked by risky and intertemporal choices, suggesting that the two domains
      utilize at least partially distinct sets of cognitive processes.

PMID- 18710654
TI  - hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma
      cells.
AB  - MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein
      expression by cleaving or repressing the translation of target mRNAs. In mammal
      animals, their function mainly represses the target mRNAs transcripts via
      imperfectly complementary to the 3' UTR of target mRNAs. Several miRNAs have been
      recently reported to be involved in modulation of glioma development, especially
      some up-regulated miRNA, such as hsa-miR-21 and hsa-miR-221. However, here we
      reported that the down-regulated hsa-miR-181a and hsa-miR-181b of hsa-miR-181
      family were also involved in oncogenesis of glioma. Our studies showed that hsa
      miR-181a and hsa-miR-181b functioned as tumor suppressors which triggered growth
      inhibition, induced apoptosis and inhibited invasion in glioma cells.
      Furthermore, the tumor-suppressive effect of hsa-miR-181b in glioma cells was
      more apparent than the effect of hsa-miR-181a. These findings suggest aberrantly
      down-regulated hsa-miR-181a and hsa-miR-181b may be critical factors that
      contribute to malignant appearance in human gliomas.

PMID- 18710655
TI  - Prenatal inflammatory effects on nigrostriatal development in organotypic
      cultures.
AB  - Maternal intrauterine infection, and the accompanying inflammation in the fetal
      brain, represent a significant risk to the developing fetus. Dopamine (DA)
      neurons have been shown to be particularly vulnerable to inflammation induced by
      injection of the bacterial endotoxin lipopolysaccharide (LPS). In order to
      further examine the nature of this vulnerability, we used a combination of in
      vivo prenatal LPS exposure, and in vitro analysis of nigrostriatal development in
      organotypic cultures prepared from LPS-exposed rat fetuses. Control co-cultures
      prepared from unexposed E14 substantia nigra (SN/VTA) and E21 striatum exhibited
      numerous DA neurons in the nigral piece and robust ingrowth into the striatal
      piece. When E14 SN/VTA was obtained from fetuses exposed to LPS (0.1 mg/kg) on
      E10, initial DA cell numbers and striatal innervation in co-cultures were normal,
      but at longer durations in vitro, a reduction in DA neurons was observed. When
      striatal tissue from fetuses exposed to LPS on E14 or E18 was used in combination
      with non-exposed SN/VTA, DA neurons initially exhibited a normal pattern of
      ingrowth into LPS-exposed striatum. However, with longer durations in vitro, DA
      neurons were lost more rapidly when co-cultured with LPS-exposed striatum.
      Despite the loss of DA neurons, striatal DA innervation was only reduced in
      cultures prepared with striatum exposed to LPS at E18, at the longest time period
      examined. Experiments in which unexposed SN/VTA was given the choice to grow
      toward control striatum or toward LPS-exposed striatum supported the idea that
      the tropic qualities of the striatum were not altered by LPS-induced
      inflammation. Thus, the inflammation induced by LPS not only affects the SN/VTA
      DA neurons, but also alters the neurotrophic--although not the neurotropic-
      characteristics of the striatum. Such alterations in nigrostriatal development
      may demonstrate how adverse perinatal events predispose the developing brain
      toward the later development of Parkinson's disease.

PMID- 18710656
TI  - Neural and behavioral correlates of drawing in an early blind painter: a case
      study.
AB  - Humans rely heavily on vision to identify objects in the world and can create
      mental representations of the objects they encounter. Objects can also be
      identified and mentally represented through haptic exploration. However, it is
      unclear whether prior visual experience is necessary to generate these internal
      representations. Subject EA, an early blind artist, provides insight into this
      question. Like other blind individuals, EA captures the external world by touch.
      However, he is also able to reveal his internal representations through highly
      detailed drawings that are unequivocally understandable by a sighted person. We
      employed fMRI to investigate the neural correlates associated with EA's ability
      to transform tactilely explored three-dimensional objects into drawings and
      contrasted these findings with a series of control conditions (e.g. nonsensical
      scribbling as a sensory-motor control). Activation during drawing (compared to
      scribbling) occurred in brain areas normally associated with vision, including
      the striate cortex along with frontal and parietal cortical regions. Some of
      these areas showed overlap when EA was asked to mentally imagine the pictures he
      had to draw (albeit to a lesser anatomical extent and signal magnitude). These
      results have important implications as regards our understanding of the ways in
      which tactile information can generate mental representations of shapes and
      scenes in the absence of normal visual development. Furthermore, these findings
      suggest the occipital cortex plays a key role in supporting mental
      representations even without prior visual experience.

PMID- 18710657
TI  - GALNS gene expression profiling in Morquio A patients' fibroblasts.
AB  - BACKGROUND: Quantification studies of mutated mRNAs have not been carried out on
      Morquio A patients. Such studies are very important for the determination of
      stability of premature termination codons (PTC) bearing transcripts in order to
      assess the appropriateness of introducing the newly developed therapeutic
      strategies such as "stop codon read-through therapy". METHODS: This paper focuses
      on the study of the GALNS gene and mRNAs in two severe forms of Morquio A
      patients' fibroblasts with development of a new and rapid real-time RT-PCR for
      detection and quantification of absolute mRNA copy number. RESULTS: We identified
      two new mutations c.385A>T (p.K129X) and c.899-1G>C) in Pt1 and a known splicing
      defect c.120+1G>A in Pt2. Using RT-PCR and real-time RT-PCR in Pt2 we detected
      low levels of mRNAs, suggesting its instability; in Pt1, we detected three
      aberrant mRNAs introducing premature stop codons, suggesting that both the
      c.385A>T and c.899-1G>C mutations produce mRNAs capable of escaping the nonsense
      mediated decay (NMD) pathway. CONCLUSIONS: The development of a real-time RT-PCR
      assay allows to absolutely quantify the GALNS mRNAs carrying mutations that lead
      to PTCs bearing transcripts, which escape the NMD process and are potentially
      suitable for the new therapeutic approach.

PMID- 18710658
TI  - Identification of mutations in the apolipoprotein B-100 gene and in the PCSK9
      gene as the cause of hypocholesterolemia.
AB  - BACKGROUND: Characterization of the normally occurring mutations as the cause of
      hypocholesterolemia may increase our understanding of the normal lipid
      metabolism. METHODS: DNA from 93 unrelated hypocholesterolemic subjects with a
      mean (+/-SD) value for total serum cholesterol of 3.3 (+/-0.5) mmol/l) were
      subjected to DNA sequencing of the individual exons of the apolipoprotein B-100
      (apoB-100) gene and of the proprotein convertase subtilisin/kexin 9 (PCSK9) gene.
      The same analyses were also performed in 23 unrelated subjects with autosomal
      dominant hypercholesterolemia who had unusually low levels of total serum
      cholesterol. RESULTS: Of the 93 hypocholesterolemic subjects, 9 subjects (9.7%)
      were heterozygous for a truncating mutation in the apoB-100 gene and six subjects
      (6.5%) were heterozygous for a loss-of-function mutation in the PCSK9 gene. Of
      the 23 subjects with autosomal dominant hypercholesterolemia, four subjects
      (17.4%) were heterozygous for mutations in the apoB-100 gene. CONCLUSION:
      Truncating mutations in the apoB-100 gene are slightly more common as the cause
      of hypocholesterolemia compared to loss-of-function mutations in the PCSK9 gene.
      It appears that mutations in the apoB-100 gene may completely normalize the lipid
      profile in subjects with autosomal dominant hypercholesterolemia, whereas loss-of
      function mutations in the PCSK9 gene do not have a sufficient cholesterol
      lowering capacity.

PMID- 18710659
TI  - Expression of chloride intracellular channel protein 1 (CLIC1) and tumor protein
      D52 (TPD52) as potential biomarkers for colorectal cancer.
AB  - OBJECTIVES: Unequivocal biomarkers are needed to predict susceptibility and
      progression of colorectal cancer. DESIGN AND METHODS: Paired samples of tumor and
      normal tissue from six patients with colorectal cancer of different localization,
      pTNM stage and grade were employed in the present study. MS analysis was used to
      identify differentially regulated proteins after 2-DE separation and
      densitometric analysis. RESULTS: Densitometric analysis revealed differential
      abundance of 55 spots in tumor as compared to normal tissues. Thirty nine out of
      55 spots were unambiguously identified by MS representing 32 different proteins.
      CLIC1, TPD52 and FABPL were consistently overexpressed (>3-fold, P<0.05) in all
      tumor tissue samples, while TPM1, TPM2, TPM3, TAGL and MLRN were consistently
      down-regulated (>3-fold, P<0.05) compared to normal tissue. CONCLUSIONS: CLIC1
      and TPD52 were significantly (P<0.05) up-regulated in all cases of colorectal
      cancer investigated, irrespective of localization, pTNM stage and grade of colon
      cancer highlighting their potential to serve as new biomarkers.

PMID- 18710660
TI  - Hairy2 functions through both DNA-binding and non DNA-binding mechanisms at the
      neural plate border in Xenopus.
AB  - The Xenopus helix-loop-helix transcription factor Hairy2 is essential for neural
      crest progenitor survival and maintains cells in a mitotic undifferentiated pre
      neural crest state. However, its mode of action remains largely unknown. Here we
      show that a Hairy2 DNA-binding mutant is unable to promote cell survival and to
      upregulate the expression of early neural border genes but is capable to increase
      cell proliferation and to expand NC in late embryos. We found that Hairy2
      transiently activates in a DNA-binding independent manner the expression of the
      Notch ligand Delta1 and that Delta1 is required for Hairy2 to promote cell
      proliferation and to expand NC. Finally, we provide evidence that Hairy2 induces
      Delta1 through the transcription factor Stat3. Together, these results suggest
      that Hairy2 has a dual mode of action and may function at the neural plate border
      through both a DNA-binding and a non-DNA-binding Stat3-Delta1 mediated mechanism.

PMID- 18710661
TI  - Kidney diseases and hypertension. Preface.

PMID- 18710662
TI  - Treatment options for end stage renal disease.
AB  - The latest National Health and Nutrition Study revealed an increasing incidence
      of kidney disease among aging baby boomers, as the incidence of diabetes mellitus
      and hypertension rises. Because of this trend, a greater proportion of a primary
      care physician's practice will involve patients with chronic kidney disease, and
      consequently, end stage renal disease. Unfortunately, far too many of these
      chronic kidney disease patients are referred to a nephrologist very late. More
      often than not, the opportunity for secondary preventive intervention, with the
      goal of avoiding renal replacement therapy, is lost. This article addresses the
      various treatment options for patients with end stage renal disease.

PMID- 18710663
TI  - Management of the kidney transplant recipient.
AB  - The short-term outcomes of kidney transplant recipients have improved
      dramatically in the past 20 years, in large part resulting from the availability
      of more potent immunosuppressive drugs capable of preventing or treating acute
      allograft rejection. Ironically, side effects from these same immunosuppressants
      play a role in the long-term morbidity and mortality of this patient population.
      As kidney transplant recipients survive for longer periods of time with
      functioning allografts, primary care physicians will likely become more involved
      in their management, mandating at least a basic understanding of
      immunosuppression and its complications.

PMID- 18710664
TI  - Management of hypertension in the outpatient setting.
AB  - The treatment of hypertension on an outpatient basis should be approached in a
      systematic manner. The diagnosis of hypertension should always be verified first
      before treatment is initiated and, where indicated, a workup should be done.
      Lifestyle modifications should be considered in all patients with hypertension.
      Blood pressure can be brought to goal in the majority of patients if
      antihypertensive medications are correctly dosed or combined. As blood pressure
      is brought to goal in the patient with hypertension, ongoing attention should be
      directed to long-term adherence to therapy.

PMID- 18710665
TI  - Hypertensive crises.
AB  - The key points of this article are: (1) A hypertensive crisis is present when
      markedly elevated blood pressure is accompanied by progressive or impending acute
      target organ damage. (2) Most instances of very elevated blood pressure
      encountered in the office setting will not be crises and will not require acute
      reduction of blood pressure. (3) Hypertensive crises are largely preventable and
      often result from inadequate management of hypertension or poor adherence to
      therapy. (4) Effective triage of patients into categories of severe hypertension,
      hypertensive urgency, and hypertensive emergency through an expeditious history,
      examination, and testing should guide therapy. (5) Hypertensive urgency is
      managed with oral medications and usually on an outpatient basis; a hypertensive
      emergency warrants intensive care unit admission and parenteral therapy. (6)
      Ensuring adequate follow-up after treatment of very elevated blood pressure is a
      critical step that is often mishandled.

PMID- 18710666
TI  - Secondary causes of hypertension.
AB  - Secondary hypertension is the presence of a specific condition known to cause
      hypertension, which may be the primary cause or a contributing factor in a
      patient who already has primary hypertension. Although uncommon, it may cause
      major morbidity for a subset of patients. This article provides an overview of
      the range of secondary causes, including key clinical features and appropriate
      diagnostic and treatment options. Selection of patients for testing should
      incorporate historical and clinical clues, previous treatment course, and
      comorbidities. Decisions regarding the extent of secondary evaluation require
      consideration of the likelihood of diagnosis, the patient's overall health status
      and prognosis, and balancing the risks of intervention against the risks of
      missing a diagnosis. Referral is advised when these risks seem prohibitive or if
      there are questions regarding the selection of the most optimal studies or the
      extent of intervention to pursue when blood pressure remains uncontrolled.

PMID- 18710667
TI  - Resistant hypertension.
AB  - Despite the high prevalence and heterogeneity of hypertension, blood pressure
      (BP) can be controlled to goal levels with effective therapy in many patients.
      However, in a small percentage of patients who have hypertension, the BP remains
      refractory to usual and customary therapeutic measures. In such patients, who
      have so-called "resistant" or "refractory" hypertension, proper evaluation and
      assessment have to be undertaken to improve the BP control. There are some
      factors that may make hypertension control difficult in some patients. Therefore,
      it is necessary to identify possible etiologic reasons for the loss of BP control
      and to rectify them to achieve normotension. In selected patients, aggressive
      treatment (nonpharmacologic and pharmacologic) of hypertension is required to
      prevent excessive morbidity and mortality.

PMID- 18710668
TI  - The trend toward geriatric nephrology.
AB  - Population aging has been accompanied by a growing burden of chronic medical
      conditions. Elderly individuals represent an increasing proportion of the total
      number of patients with chronic kidney disease, acute renal failure, and end
      stage renal disease. In addition, age-related changes in the kidneys and other
      organ systems predispose the older person to disturbances in fluid and
      electrolyte balance, which exacerbate renal dysfunction. This article reviews the
      evolving epidemiology of renal disorders among the elderly and summarizes
      evidence put forward to explain this phenomenon.

PMID- 18710669
TI  - Classification and epidemiology of childhood sleep disorders.
AB  - Approximately 25% of all children experience some type of sleep problem at some
      point during childhood. A number of studies have examined the prevalence of
      parent- and child-reported sleep complaints in large samples of healthy,
      typically developing children and adolescents; many of these have also further
      delineated the association between disrupted sleep and behavioral concerns. Sleep
      problems are even more prevalent in children and adolescents with chronic
      medical, neurodevelopmental, and psychiatric conditions. It is important to note
      that definitions of normal sleep patterns, sleep requirements, and sleep
      disorders in childhood must necessarily incorporate the wide range of normal
      developmental and physical maturational changes across childhood and adolescence,
      and cultural, environmental, and social influences.

PMID- 18710670
TI  - Infant crying and sleeping: helping parents to prevent and manage problems.
AB  - This article summarizes the current understanding of infant crying and sleeping
      problems, together with the implications of this understanding for services and
      research, with a focus on the first months of infancy.

PMID- 18710671
TI  - Bedtime problems and night wakings in children.
AB  - Bedtime problems and night wakings in children are extremely common, and the
      treatment literature demonstrates strong empirical support for behavioral
      interventions. Empirically validated interventions for bedtime problems and night
      wakings include extinction, graduated extinction, positive routines, and parental
      education. Most children respond to behavioral interventions, resulting not only
      in better sleep for the child, but also better sleep and improved daytime
      functioning for the entire family. This article reviews the presentation of
      bedtime problems and night wakings, empirically validated interventions, and
      challenges to treatment in both typically developing and special populations of
      children.

PMID- 18710672
TI  - Who's Smoking? Cotinine versus self-report in adolescent populations.

PMID- 18710673
TI  - Oral sexual behavior: harm reduction or gateway behavior?

PMID- 18710674
TI  - Connectedness in the lives of children and adolescents: a call for greater
      conceptual clarity.
AB  - Studies of the role of connectedness in the health and development of children
      and adolescents are accumulating rapidly. Although findings are uniformly
      consistent in documenting its correlation with a host of health indicators, the
      construct is in need of substantial conceptual clarification to maximize its
      research and applied utility. Current conceptualizations and operationalizations
      inconsistently span a wide spectrum of varied elements of social experience-
      including the quality of a relationship, the degree of liking an environment or
      relationship, the quality of performance in an environment or relationship, the
      possession of feelings or attitude states, and a combination of states and the
      behaviors that antecede them--resulting in an ability to adequately understand
      what the construct is and how, why, and when it is most protective. This paper
      documents this variability in an effort to sensitize researchers, practitioners,
      and policy makers to the complexity of the construct. It further describes one
      ongoing, multicultural research project that is currently informing international
      health initiatives as an illustration of one approach to addressing the
      complexity with goals of precision, parsimony, cultural sensitivity, and applied
      utility.

PMID- 18710675
TI  - Infective endocarditis after body art: a review of the literature and concerns.
AB  - PURPOSE: Infective endocarditis (IE) is a rare but dangerous complication of
      tattooing and body piercing in adolescents and young adults 15-30 years of age,
      with and without congenital heart disease (CHD). Because body art, including
      tattooing and piercing, is increasing and IE cases continue to be reported in the
      literature, a longitudinal assessment of IE and body art cases is important to
      examine for trends. METHODS: A 22-year (1985-2007) longitudinal electronic
      Medline and Scopus review of all published cases of IE and body art was
      conducted. RESULTS: In all, 22 specific cases of IE spanning 1991-2007 have been
      reported that were associated with piercing the tongue (seven), ear lobes (six),
      navel (five), lip (one), nose (one), and nipple (one), and reported in one
      heavily tattooed person; other general IE cases have also been mentioned. Twelve
      cases were in females, and one patient died; nine of these individuals had CHD.
      Twenty-one cases have been published in the 10 years from 1997-2007. CONCLUSIONS:
      Although there is no denominator to assess the real risk, this review provides
      more evidence of IE and body art concerns, and should stimulate further
      discussion regarding IE antibiotic prophylaxis. It is believed that IE is
      triggered by normal flora at the body art site, microorganism colonization around
      the jewelry, or by a localized site infection that stimulates episodes of
      transient bacteremia (commonly caused by staphylococi) and then seeds various
      areas of the heart. Frequently in such cases the mitral or aortic valves need to
      be replaced. For individuals with CHD who want body art, prophylactic antibiotic
      regimens have been suggested since 1999. Millions of tattoos and body piercings
      are done yearly, and more IE cases are therefore suspected. An international
      electronic repository of body art complications would provide better
      documentation. Body art procurement for many persons in this age group is a
      matter of "when, not if"; thus proactive, frequent, targeted educational
      strategies for adolescents and artists practicing body art are suggested.

PMID- 18710676
TI  - Agreement between self-reported smoking and cotinine concentration in
      adolescents: a validation study in Brazil.
AB  - PURPOSE: To validate self-reported data on smoking in adolescents in comparison
      with cotinine concentration. METHODS: Two thousand two hundred nine seventh- and
      eighth-grade students from 32 public schools in Pelotas, Brazil. Adolescents were
      contacted twice--before and after an educational intervention--and samples of
      urine for cotinine analyses were taken. In this paper, only data from the
      baseline phase are presented. High-performance liquid chromatography was used for
      cotinine analysis. Two cutoff points for cotinine were used: 10 ng/mL and 30
      ng/mL. Two self-reported smoking variables were used: at least one cigarette
      smoked in the previous 30 days; and daily smoking. RESULTS: The self-reported
      prevalence of smoking in the previous 30 days was 7.4%, and 0.9% of the
      adolescents reported to be daily smokers. Those who reported smoking in the
      previous 30 days presented mean cotinine values 10 times greater than those who
      reported to be nonsmokers. Using a cutoff of 10 ng/mL for cotinine, sensitivity
      of self-reported smoking was 16.3% (95% confidence interval [CI] 11.7; 20.9) and
      specificity was 93.6% (95% CI 92.8; 95.0). Using a cutoff of 30 ng/mL,
      sensitivity was 22.6% (95% CI 15.6; 29.6) and specificity was 93.7% (95% CI 92.6;
      94.8). CONCLUSIONS: Self-reported smoking presents low agreement with cotinine
      concentration, suggesting that adolescents underestimate tobacco consumption.

PMID- 18710677
TI  - Noncoital sexual activities among adolescents.
AB  - PURPOSE: Although prior research has demonstrated that many adolescents engage in
      noncoital sexual behavior, extant peer-reviewed studies have not used nationally
      representative data or multivariate methods to examine these behaviors. We used
      data from Cycle 6 of National Survey of Family Growth (NSFG) to explore factors
      related to oral and anal sex among adolescents. METHODS: Data come from 2,271
      females and males aged 15-19 in 2002. Computer-assisted self-administered
      interviews were used to collect sensitive information, including whether
      respondents had ever engaged in vaginal, oral or anal sex. We used t tests and
      multivariate logistic regression to test for differences and identify independent
      characteristics associated with experience with oral or anal sex. RESULTS: In
      all, 54% of adolescent females and 55% of adolescent males have ever had oral
      sex, and one in 10 has ever had anal sex. Both oral sex and anal sex were much
      more common among adolescents who had initiated vaginal sex as compared with
      virgins. The initiations of vaginal and oral sex appear to occur closely
      together; by 6 months after first vaginal intercourse, 82% of adolescents also
      engaged in oral sex. The strongest predictor of anal sex involvement was time
      since initiation of vaginal sex and the likelihood of anal sex increased with
      greater time since first vaginal intercourse. Teens of white ethnicity and higher
      socioeconomic status were more likely than their peers to have ever had oral or
      anal sex. CONCLUSIONS: Health professionals and sexual health educators should
      address noncoital sexual behaviors and risk for sexually transmitted infections
      risk, understanding that noncoital behaviors commonly co-occur with coital
      behaviors.

PMID- 18710678
TI  - Uptake of HPV vaccine: demographics, sexual history and values, parenting style,
      and vaccine attitudes.
AB  - PURPOSE: To examine the relationships of demographics, parenting, and vaccine
      attitudes with the acceptance of the human papillomavirus (HPV) vaccine or to the
      intent to vaccinate in the next 12 months. METHODS: Mothers (n = 153) with
      daughters ages 11 to 17 years were recruited through the pediatric clinic waiting
      room/announcements to complete a questionnaire. RESULTS: Eighteen percent of the
      daughters had not received the vaccine, although it had been offered; 34% had not
      been offered the vaccine and did not intend to get it in the next 12 months; 22%
      had not been offered the vaccine but intended to get it in the next 12 months;
      26% had started vaccination or completed the series. In a multinomial,
      multivariable logistic regression model, those mothers who had less than a high
      school degree, had a history of a sexually transmitted infection, supervised
      their daughter more when she was with peers, and whose daughter would not mind
      three shots were more likely to be favorable about their daughter being
      vaccinated. The following variables were not related to their attitudes about
      getting the vaccine: mothers' and daughters' ages, race/ethnicity, mothers' self
      reported history of HPV disease and age of sexual initiation, daughters' dating
      status and anticipated age of sexual initiation, the number of sexual topics
      discussed and level of comfort, mother's sexual values, and the family
      environment. CONCLUSIONS: Mothers' decisions about the HPV vaccine were not
      related to their sexual values or their daughters' sexual behavior, but rather
      their parenting, sense of vulnerability, and vaccine attitudes. Mothers who were
      not planning to vaccinate did not appear to not feel an urgency given the newness
      of the vaccine, and many planned to vaccinate eventually.

PMID- 18710679
TI  - Adolescent risk taking, neighborhood social capital, and health.
AB  - PURPOSE: To assess the roles of a neighborhood measure of social capital, family
      affluence, and risk taking on adolescent self-rated health. METHODS: This study
      uses data from the 2384 Canadian students in Grades 9-10 (56.5% female) from the
      World Health Organization's Health Behavior in School-Aged Children Survey
      2001/2002, a nationwide representative sample. RESULTS: Using binary logistic
      regression models, it is found that higher levels of risk taking and lower levels
      of neighborhood social capital and family affluence are independently associated
      with worse overall perceptions of health. These influences are not found to
      interact with each other. CONCLUSIONS: Neighborhood social capital, risk taking,
      and family affluence are important factors to consider when addressing the health
      of adolescents. Results are discussed in terms of possible health promoting
      interventions.

PMID- 18710680
TI  - Ethiopian adolescents' attitudes and expectations deviate from current infant and
      young child feeding recommendations.
AB  - PURPOSE: Suboptimal infant and child feeding practices are highly prevalent in
      many developing countries for reasons that are not entirely understood. Taking an
      anthropological perspective, we assessed whether nulliparous youth have
      formulated attitudes and expectations in the domain of infant and child feeding
      behaviors, the extent to which these varied by location and gender, and the
      extent to which they deviated from current international recommendations.
      METHODS: A population-based sample of 2077 adolescent girls and boys (13-17
      years) in southwest Ethiopia answered a questionnaire on infant and young child
      feeding behaviors. RESULTS: Results indicate high levels of agreement among
      adolescents on items relating to infant and young child feeding behaviors.
      Attitudes and intentions deviated widely from current international
      recommendations. Youth overwhelmingly endorsed items related to early
      introduction of nonbreast milk liquids and foods. For girls, fewer than 11%
      agreed that a 5-month infant should be exclusively breastfed and only 26% agreed
      that a 6-month infant should be consuming some animal source foods. Few sex
      differences emerged and youth responses matched larger community patterns.
      CONCLUSIONS: The results indicate that attitudes and expectations deviate widely
      from current international child feeding guidelines among soon to be parents. To
      the extent that youth models are directive, these findings suggest that youth
      enter into parenthood with suboptimal information about infant and child feeding.
      Such information will reproduce poor health across generations as the largest
      cohort of adolescents ever become parents. These results suggest specific points
      of entry for adolescent nutrition education interventions.

PMID- 18710681
TI  - Association between mental and physical health problems in high-risk adolescents:
      a longitudinal study.
AB  - PURPOSE: This longitudinal study examined the relationship between mental and
      physical health problems in a sample of high-risk youth served in the public
      sector. METHODS: Participants included youth aged 9-18 years at baseline,
      randomly sampled from one of five public service sectors in San Diego County,
      California, and youths may have been active to more than one sector. Diagnoses
      for mood, anxiety, and disruptive disorders based on structured diagnostic
      interviews were determined at baseline and data regarding health-related problems
      were collected 2 years post-baseline. RESULTS: Mood and disruptive behavior
      disorders were related to cumulative health problem incidence, as well as
      aggregate measures of health problems and severe health problems. In addition
      mood disorder diagnosis was associated with higher rates of infectious diseases,
      respiratory problems, and weight problems. Disruptive disorder diagnosis was
      related to higher rates of risk behavior-related health problems. CONCLUSIONS:
      The present work extends the research on the relationship between mental and
      physical health problems to adolescents served in the public sector, who are at
      especially high risk for behavioral and emotional problems. Potential mechanisms
      by which mental health problems may impact health problems are discussed. We
      suggest the development of effective interagency cooperation between medical and
      mental health systems to improve the care of youth with comorbid mental and
      physical disorders.

PMID- 18710682
TI  - Use of mental health counseling as adolescents become young adults.
AB  - PURPOSE: Despite parallels in mental health needs among adolescents and young
      adults, there is a paucity of evidence regarding use of mental health services in
      young adulthood. Using a longitudinal sample, this study compares rates of mental
      health counseling use between adolescents and young adults, examines
      characteristics and predictors of counseling use for young adults, and identifies
      reasons for foregone care among those with mental health needs in young
      adulthood. METHODS: Secondary data analysis was conducted on a nationally
      representative sample of 10,817 participants from the National Longitudinal Study
      of Adolescent Health. Data were derived from an initial survey collected in 1995
      (mean age, 15.8 years) and a follow-up survey collected 7 years later (mean age,
      21.5 years). RESULTS: Among individuals with depressive symptomology, young
      adults reported significantly lower rates of counseling use compared with
      adolescents. When taking into account the severity of mental health problems,
      female gender, high maternal education, school attendance, and receipt of routine
      physical examinations were significantly predictive of counseling use among young
      adults. Young adults of black ethnicity were significantly less likely to receive
      counseling compared with those of white ethnicity. Overall, 4% of young adults
      reported foregoing health care in the past year, despite self-reported mental
      health needs. Inability to pay, belief that the problem would go away, and lack
      of time were commonly cited reasons for any type of foregone health care.
      However, concerns regarding physician's care (i.e., fear of what the doctor would
      say or do, and belief that the doctor would be unable to help) were more
      frequently mentioned by those who acknowledged a need for counseling services.
      CONCLUSIONS: Low rates of mental health counseling persist from adolescence to
      young adulthood. Findings such as increased counseling service use among those
      receiving routine physical examinations, as well as reported concerns of
      physician care, point to possible areas of intervention within the pediatric
      community.

PMID- 18710683
TI  - A federal monitoring system for early adult health.
AB  - Federal statistical agencies have spent decades developing a robust system for
      monitoring the health of America's adolescents at the national and state levels.
      More recently, the health of young adults (roughly 18-24 years of age) has
      received greater attention in public health and health policy discussions, yet
      relatively little is known about the nation's capacity to effectively monitor the
      health of this age group. This article reviews existing federal data collection
      efforts and reporting systems to identify what pieces currently exist to support
      an effective health monitoring system for young adults and what is still needed,
      and makes recommendations for enhancing the current system by improving data
      access and quality. In particular, a major step toward establishing a
      recognizable health monitoring system for young adults can be taken simply by
      pulling together existing data into organized chartbooks and web portals that
      focus on this age group.

PMID- 18710684
TI  - Violence involvement, substance use, and sexual activity among Mexican-American
      and European-American adolescents.
AB  - PURPOSE: This study examined longitudinal associations between violence
      involvement, substance use, and sexual activity. METHODS: A total of 302 urban
      Mexican-American and European-American adolescents were randomly selected and
      recruited from the membership lists of a large health maintenance organization.
      Data were obtained from interviews conducted when the mean ages of adolescents
      were 15, 18, and 19 years. RESULTS: Independent of age, gender, ethnicity, family
      socioeconomic status, and previous levels of health risk behavior, adolescents
      who had been victimized by violence at age 15 were more likely to use tobacco at
      age 19. Adolescents who had been victimized by or perpetrated violence at age 18
      had a greater number of sexual partners and were more likely to use marijuana at
      age 19. In addition, adolescents who had perpetrated violence at age 18 engaged
      in greater alcohol use at age 19. A second set of analyses showed that
      independent of demographics and previous violence involvement, adolescents who
      had used marijuana at age 15 were more likely to report violence involvement at
      age 19. Adolescents who had used tobacco or who had a greater number of sexual
      partners at ages 15 or 18 were more likely to report violent victimization at age
      19. CONCLUSIONS: Associations between violence involvement and other forms of
      health risk behavior are bidirectional. Adolescents involved with violence are at
      risk for increases in substance use and sexual behavior over time. Adolescents
      who engage in substance use and sexual behavior with multiple partners are also
      at risk for later violence involvement.

PMID- 18710685
TI  - Drug use among homeless young people in Los Angeles and Melbourne.
AB  - PURPOSE: To examine the effect of time spent homeless on young people's substance
      use and use of drug and alcohol services in two countries with contrasting policy
      and service environments. METHODS: A crossnational survey was conducted of
      recently homeless and experienced homeless young people in Melbourne (N = 674)
      and Los Angeles (N = 620). Questions were asked about alcohol and drug use in the
      past 3 months, frequency of use, injecting drug use, drug dependency, and
      perceived need for, and use of, drug and alcohol services. Data were analyzed
      using logistic regression. RESULTS: Substantial numbers of young people reported
      use of alcohol and drugs. More Australians than Americans and more experienced
      than newly homeless reported drug use, although there were no differences in
      frequency of use in the past 3 months. Polydrug use was common, as were injecting
      drugs and responses that signified drug dependency. All were more common among
      Australians and experienced homeless young people. A substantial number of young
      people had "ever" taken part in a drug or alcohol program, but only a minority
      believed that they needed help from services. Of these, only a minority had
      sought help. This was particularly so among those who were classified as drug
      dependent. Reasons for failure to seek help varied. CONCLUSION: Substance use is
      alarmingly high compared to national samples of young people, especially among
      those who had been homeless for longer periods. Programs to reduce substance use
      must take account of the prevailing drug cultures, as well as different subgroups
      of the population.

PMID- 18710686
TI  - Prevalence of self-reported human immunodeficiency virus testing among a
      population-based sample of urban African-American adolescents.
AB  - We explored the prevalence of gender differences in human immunodeficiency virus
      (HIV) testing among a household sample of sexually active African-American
      adolescents. Females disproportionately self-report being tested for HIV more
      than males. This difference was not explained by age or receipt of services for
      sexually transmitted infection but was partially attributable to history of
      pregnancy.

PMID- 18710687
TI  - Internet referrals for adolescent violence prevention: an innovative mechanism
      for inner-city emergency departments.
AB  - Internet referrals provide a potential solution to limited staff time in
      emergency departments for health education. One hundred fifteen adolescents were
      surveyed and referred to a violence prevention website; 22% logged on the
      website. Although this study bears replication, Internet referral may be a low
      intensity intervention that could compliment other violence prevention strategies
      among adolescents.

PMID- 18710688
TI  - Distraction osteogenesis for maxillofacial surgeons. Preface.

PMID- 18710689
TI  - The influence of mechanical environment on bone healing and distraction
      osteogenesis.

PMID- 18710690
TI  - Distractor design and options.

PMID- 18710691
TI  - Intra-arch distraction.

PMID- 18710692
TI  - Alveolar modification by distraction osteogenesis.

PMID- 18710693
TI  - Vertical and horizontal mandibular lengthening of the ramus and body.

PMID- 18710694
TI  - Maxillary advancement by distraction osteogenesis.

PMID- 18710695
TI  - Midfacial distraction osteogenesis.

PMID- 18710696
TI  - Orthopedic and orthodontic management of distal segment position during
      distraction osteogenesis.

PMID- 18710697
TI  - Mandible reconstruction with transport distraction osteogenesis.

PMID- 18710698
TI  - Quality of life after abdominal aortic aneurysm repair: similar long-term results
      with endovascular and open techniques.

PMID- 18710699
TI  - The measurement of impairment due to eating disorder psychopathology.
AB  - Eating disorders have a profound and highly specific impact on psychosocial
      functioning. The aim of this research was to develop a measure of such secondary
      impairment. A 16-item, self-report instrument was developed, the Clinical
      Impairment Assessment (CIA), which was designed to measure such impairment
      overall and in three specific domains (personal, cognitive, social). The
      psychometric properties of the instrument were evaluated using data collected in
      the context of a transdiagnostic treatment trial. The findings consistently
      supported the utility of the instrument with the CIA being shown to have high
      levels of internal consistency, construct and discriminant validity, test-retest
      reliability, and sensitivity to change. The CIA should be of value to clinicians
      when assessing patients with eating disorders and their response to treatment. It
      should also help inform epidemiological research.

PMID- 18710700
TI  - Evidence for an explanation advantage in naive biological reasoning.
AB  - The present studies compare young children's explanations and predictions for the
      biological phenomenon of contamination. In Study 1, 36 preschoolers and 24 adults
      heard vignettes concerning contamination, and were asked either to make a
      prediction or to provide an explanation. Even 3-year-olds readily supplied
      contamination-based explanations, and most children mentioned an unseen mechanism
      (germs, contact through bodily fluids). Moreover, unlike adults who performed at
      ceiling across both explanation and prediction tasks, children were significantly
      more accurate with their explanations than their predictions. In Study 2, we
      varied the strength of cues regarding the desirability of the contaminated
      substance (N=24 preschoolers). Although desirability affected responses, for both
      levels of desirability participants were significantly more accurate on
      explanation than prediction questions. Altogether, these studies demonstrate a
      significant "explanation advantage" for children's reasoning in the domain of
      everyday biology.

PMID- 18710701
TI  - The effect of CO2 insufflation-desufflation attacks on tissue oxidative stress
      markers during laparoscopy: a rat model.
AB  - OBJECTIVE: To determine the effects of sudden intra-abdominal pressure (IAP)
      changes on the terminal ileum in a pneumoperitoneum model. DESIGN: An
      experimental controlled study. SETTING: University hospital in Turkey. ANIMAL(S):
      Thirty-two adult female Sprague-Dawley rats. INTERVENTION(S): The rats were
      divided into four groups. Group 1 was not subjected to IAP. In group 2, IAP
      insufflation was performed continuously to keep the IAP at 10 mmHg. Groups 3 and
      4 underwent an insufflation-desufflation procedure: group 3 was fluctuated 5
      times, and group 4 was fluctuated 10 times within the pneumoperitoneum period of
      60 minutes. Thirty minutes after the desufflation, the terminal ileum was removed
      for the measurement of tissue malondialdehyde (MDA) values and histopathological
      examination. MAIN OUTCOME MEASURE(S): The tissue MDA values and histopathological
      damage scores. RESULT(S): The tissue MDA values in the IAP groups (groups 2, 3,
      and 4) were significantly increased when compared with those of the control
      group. The mean MDA value in group 4 was higher than that in groups 2 and 3.
      Histopathologic oxidative damage scores in the mucosa and submucosal layers were
      significantly higher in groups 2 and 3, compared with those of the control group.
      However, the highest histopathologic damage scores were observed in group 4.
      CONCLUSION(S): Unexpected desufflation-insufflation even at normal IAP levels
      during laparoscopy leads to significant oxidative stress-induced damage in the
      terminal ileum.

PMID- 18710702
TI  - Expressions of steroid receptors and Ki67 in first-trimester decidua and
      chorionic villi exposed to levonorgestrel used for emergency contraception.
AB  - Levonorgestrel (1.5 mg) is commonly used for emergency contraception to prevent
      an unwanted pregnancy after an unprotected intercourse. We found that
      postovulatory administration of 1.5 mg of levonorgestrel to women with a
      subsequent or existing early pregnancy did not affect the immunohistochemical
      expressions of estrogen receptors (ER(alpha), ER(beta)), P receptors (PR(B),
      PR(A+B)), androgen receptor (AR), or proliferation index Ki67 in the first
      trimester decidua and chorionic villi.

PMID- 18710703
TI  - The challenge of providing infertility services to a low-income immigrant Latino
      population.
AB  - OBJECTIVE: To provide insight into the experience of low-income immigrant Latino
      couples seeking infertility treatment. DESIGN: Qualitative interview study.
      SETTING: Infertility clinic at a university-affiliated urban public teaching
      hospital. PATIENT(S): Infertile low-income immigrant Latino couples (105 women
      and 40 men). INTERVENTION(S): In-depth, tape-recorded interviews. MAIN OUTCOME
      MEASURE(S): After transcription and translation, the interviews were coded and
      analyzed for thematic content. RESULT(S): Four major challenges to providing
      infertility services to this population were identified: [1] communication:
      language and cultural barriers resulted in patients having difficulty both in
      understanding diagnoses and treatments and in communicating their questions,
      concerns, and experiences to physicians; [2] continuity: because medical students
      and residents rotated frequently, patients usually saw a different physician at
      each visit; [3] bureaucracy: patients reported having difficulty with appointment
      scheduling, follow-up visits, and timed laboratory procedures; and [4]
      accessibility: patients faced issues of limited availability and affordability of
      treatment. CONCLUSION(S): At a large, urban, university-affiliated infertility
      clinic, challenges related to communication, comprehension, continuity,
      bureaucracy, accessibility, availability, and affordability impeded the delivery
      of optimal infertility care to many low-income immigrant Latino patients. A
      greater availability of translators and both patient and physician cultural
      orientations to address these health care barriers is recommended.

PMID- 18710704
TI  - Involvement of nuclear factor-kappaB in macrophage migration inhibitory factor
      gene transcription up-regulation induced by interleukin- 1 beta in ectopic
      endometrial cells.
AB  - OBJECTIVE: To investigate the involvement of the nuclear factor (NF)-kappaB in
      the interleukin (IL)-1 beta-mediated macrophage migration inhibitory factor (MIF)
      gene activation. DESIGN: Prospective study. SETTING: Human reproduction research
      laboratory. PATIENT(S): Nine women with endometriotic lesions. INTERVENTION(S):
      Endometriotic lesions were obtained during laparoscopic surgery. MAIN OUTCOME
      MEASURE(S): The MIF protein secretion was analyzed by ELISA, MIF mRNA expression
      by quantitative real-time polymerase chain reaction (PCR), NF-kappaB
      translocation into the nucleus by electrophoresis mobility shift assay, I kappaB
      phosphorylation and degradation by Western blot, and human MIF promoter activity
      by transient cell transfection. RESULT(S): This study showed a significant dose
      dependent increase of MIF protein secretion and mRNA expression, the NF-kappaB
      translocation into the nucleus, I kappaB phosphorylation, I kappaB degradation,
      and human MIF promoter activity in endometriotic stromal cells in response to IL
      1 beta. Curcumin (NF-kappaB inhibitor) significantly inhibited all these IL-1
      beta-mediated effects. Analysis of the activity of deletion constructs of the
      human MIF promoter and a computer search localized two putative regulatory
      elements corresponding to NF-kappaB binding sites at positions -2538/-2528 bp and
      -1389/-1380 bp. CONCLUSION(S): This study suggests the involvement of the nuclear
      transcription factor NF-kappaB in MIF gene activation in ectopic endometrial
      cells in response to IL-1 beta and identifies a possible pathway of endometriosis
      associated inflammation and ectopic cell growth.

PMID- 18710706
TI  - Evaluation of chemiluminescence and flow cytometry as tools in assessing
      production of hydrogen peroxide and superoxide anion in human spermatozoa.
AB  - OBJECTIVE: To examine simultaneously the levels of hydrogen peroxide (H(2)O(2))
      and superoxide (O(2)(-*)) using chemiluminescence and flow cytometry. DESIGN:
      Prospective laboratory study. SETTING: Reproductive research lab in a tertiary
      hospital. PATIENT(S): Semen samples from 18 healthy male volunteers.
      INTERVENTION(S): Sperm preparation and measurement of reactive oxygen species
      (ROS) by chemiluminescence using luminol and lucigenin before and after H(2)O(2)
      exposure and by flow cytometry using dichlorofluorescin diacetate (DCFH-DA) for
      H(2)O(2) and dihydroethidium (DHE) for O(2)(-*). MAIN OUTCOME MEASURE(S): Sperm
      count, motility, viability, and ROS levels. RESULT(S): Immature sperm fractions
      showed significantly higher levels of ROS measured by either luminol or lucigenin
      compared with the neat and mature fraction. ROS levels were detectable by flow
      cytometry in chemiluminescence-negative samples. Both mature and immature sperm
      fractions had a significantly higher percentage of cells positive for H(2)O(2)
      compared with neat semen. On the other hand, the percentage of O(2)(-*)-positive
      cells in neat semen was significantly higher compared with the percentage found
      in mature fractions but significantly lower than that in the immature sperm
      fractions. CONCLUSION(S): We recommend ROS measurement by flow cytometry on the
      basis that it requires a lower sperm count, is comparable to chemiluminescence,
      and has higher specificity for intracellular ROS in viable spermatozoa. Samples
      tested negative by chemiluminescence still may have high intracellular H(2)O(2)
      generation that can be detected by flow cytometry.

PMID- 18710705
TI  - Bovine serum albumin contained in culture medium used in artificial insemination
      is an important anaphylaxis risk factor.
AB  - OBJECTIVE: To analyze the cause of the anaphylactic reaction after a standard
      artificial insemination process in a patient diagnosed with asthma. DESIGN: Case
      report. SETTING: Residencia Sanitaria Virgen de la Arrixaca (Murcia, Spain) and
      University of the Basque Country (Vitoria, Spain). PATIENT(S): A 30-year-old
      woman with a previous medical history compatible with respiratory allergy who
      suffered an anaphylactic reaction after an artificial insemination with
      spermatozoids in capable medium (Upgraded B2 INRA medium; Laboratories CCD,
      Paris, France). INTERVENTION(S): Cutaneous tests and specific IgE levels to
      inhalant allergens, grass and Olea pollens, and insemination medium were
      performed. MAIN OUTCOME MEASURE(S): Specific IgE levels to mammal epithelia and
      bovine serum albumin (BSA). RESULT(S): Skin prick tests were positive for
      inhalant allergens such as mites, cat, dog, horse, and rabbit epithelia, grasses
      and Olea pollens, and the insemination medium. The beta-lactamic tests were
      negative. The determination of specific IgE demonstrated positive values to
      mammal epithelia and mammal serum albumins including BSA. CONCLUSION(S): We
      report a case of an anaphylactic reaction to the BSA included in the insemination
      culture medium induced by a subclinical sensitivity to serum albumins of mammal
      epithelia. A previous testing with the medium is recommended and specific testing
      might be needed in women who have a history of animal epithelium allergies.

PMID- 18710707
TI  - Transvaginal hydrolaparoscopy in the treatment of polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the efficacy of transvaginal endoscopic ovarian capsule
      drilling. DESIGN: Retrospective efficacy study. SETTING: Private tertiary care
      center. PATIENT(S): Thirty-nine PCOS patients with previously failed ovulation
      induction; mean duration of infertility 26.5 months (SD +/-2.6); mean age 30.38
      years (SD +/-3.8); mean body mass index of 29.4 (SD +/-9.7). INTERVENTION(S):
      Through transvaginal hydrolaparoscopy in a 1-day clinic setting, drilling of the
      ovarian capsule is performed with a 5-Fr bipolar needle (Karl Storz, Tuttlingen,
      Germany) creating 10-15 holes of +/-0.20 mm in each ovary. MAIN OUTCOME
      MEASURE(S): Evaluation of feasibility, spontaneous resumption of ovulatory cycles
      and pregnancy rates. RESULT(S): Ovarian capsule drilling was performed in 39
      patients. Six patients were lost of follow-up. In total, 25 out of 33 patients
      (76%) became pregnant with a mean duration between procedure and onset of
      pregnancy of 7.2 months (SD +/-5.4). Natural conception with or without
      controlled ovarian hyperstimulation and/or intrauterine insemination occurred in
      13 of the 16 patients (81%). Of the 17 patients referred to our IVF program, 12
      became pregnant. There were no multiple pregnancies or complications.
      CONCLUSION(S): The transvaginal approach for ovarian capsule drilling offers a
      valuable alternative to the standard laparoscopic procedure.

PMID- 18710708
TI  - Cryopreservation has no effect on meiotic recombination and synapsis in
      testicular tissues.
AB  - The effects of cryopreservation on meiotic progression, synapsis, recombination,
      and structure of synaptonemal complexes (SCs) in testicular tissues were
      evaluated by comparing the above-mentioned parameters in frozen and fresh
      testicular tissues from the same men. No differences in meiotic progression, the
      mean number of MLH1 foci per cell, the mean number of autosomal SCs with
      different numbers of MLH1 foci, or the fidelity of the synapsis were observed
      between fresh and frozen testicular tissues.

PMID- 18710709
TI  - Insulin resistence and health-related quality of life in postmenopausal women.
AB  - Health-related quality of life (HR-QOL) was similar between the menopausal women
      with and without Insulin Resistance (IR). However, when IR women with Metabolic
      Syndrome were considered, a higher level of problems on the HR-QOL global score
      was found and the difference was mainly due to Health and Sexuality domains.

PMID- 18710710
TI  - Influence of progesterone on endometrial nitric oxide synthase expression.
AB  - OBJECTIVE: To determine the effect of P on nitric oxide synthase (NOS) expression
      in human endometrial epithelial cells. DESIGN: Laboratory-based study. SETTING:
      University-based research institute. PATIENT(S): None. INTERVENTION(S): The
      effect of P on the expression of NOS protein isoforms was examined in an in vitro
      preparation. MAIN OUTCOME MEASURE(S): The expression of NOS and phosphorylated
      endothelial NOS (peNOS) protein in human endometrial-derived epithelial cells
      (HES cells) and messenger RNA (mRNA) in human primary endometrial cell culture.
      RESULT(S): Progesterone induced a concentration- and time-dependent stimulation
      of endothelial NOS (eNOS), inducible NOS (iNOS), and peNOS protein in HES cells.
      Progesterone also stimulated eNOS and iNOS mRNA in human primary endometrial
      cells. The effect of P on eNOS and iNOS was completely blocked by RU486 but was
      partially blocked in case of phosphorylated eNOS. RU486 alone had an inhibitory
      effect on expression of eNOS but not iNOS protein at a concentration of 10(-5)
      mol/L. Progesterone stimulated phosphorylation of eNOS within 30 minutes, and
      this effect was completely blocked by an inhibitor of PI3/Akt pathway,
      wortmannin, and by the extracellular signal-regulated kinase 1,2 pathway blocker
      UO126. CONCLUSION(S): Progesterone has both genomic and nongenomic effects to
      stimulate the expression of NOS in HES cells. The nongenomic action of P on NOS
      phosphorylation is mediated by the PI3/Akt and extracellular signal-regulated
      kinase 1,2 pathways.

PMID- 18710711
TI  - Combined jugular and subclavian vein thrombosis following assisted reproductive
      technology--new observation.
AB  - OBJECTIVE: To study the predilection of jugular and subclavian vein thrombosis in
      patients going through assisted reproductive technology (ART). This technology
      puts women at high risk of developing the ovarian hyperstimulation syndrome
      (OHSS) and thrombotic events. DESIGN: Study cases. SETTING: Large Academic
      Medical Center. PATIENT(S): Five women who developed jugular and subclavian vein
      thrombosis following ART were included in the study. INTERVENTION(S): The deep
      vein thrombosis was demonstrated by ultrasound Doppler or computerized tomography
      angiography. All women were interviewed and data obtained from outpatient and
      hospital medical charts. Magnetic resonance imaging and complete thrombophilic
      profile workup was performed in each woman. Open biopsy from the lesions was
      taken from one of the women. MAIN OUTCOME MEASURE(S): Correlation between
      mechanical branchial cysts filled with fluid during OHSS and jugular and
      subclavian vein thrombosis. RESULT(S): Five women developed jugular and
      subclavian vein thrombosis following ART. They were found to harbor clusters of
      rudimentary branchial cysts filled with fluid at the time of OHSS, which
      compressed the jugular and subclavian veins at their junction at the base of the
      neck. Four patients (80%) were found to be carriers of factor V Leiden.
      CONCLUSION(S): Predilection of jugular and subclavian vein thrombosis early in
      pregnancy is the result of mechanical compression mediated by rudimentary
      branchial cysts filled with fluid during OHSS, particularly in subjects who are
      carriers of factor V Leiden.

PMID- 18710712
TI  - Recombinant human leukemia inhibitory factor does not improve implantation and
      pregnancy outcomes after assisted reproductive techniques in women with recurrent
      unexplained implantation failure.
AB  - In this randomized, double-blind, placebo-controlled, multicenter study, women (n
      = 149) with a history of at least two unexplained implantation failures after
      assisted reproductive techniques received recombinant human leukemia inhibitory
      factor, 150 microg SC twice daily for 7 days, or placebo. The clinical pregnancy
      rate after ET was significantly lower in patients receiving recombinant human
      leukemia inhibitory factor than in those receiving placebo (17.6% vs. 34.0%,
      respectively).

PMID- 18710713
TI  - Risk of gestational diabetes mellitus in women with polycystic ovary syndrome: a
      systematic review and a meta-analysis.
AB  - OBJECTIVE: To evaluate the risk of gestational diabetes mellitus (GDM) in women
      with polycystic ovary syndrome (PCOS). DESIGN: Systematic review and meta
      analysis of observational studies. SETTING: Tertiary Department of Reproductive
      Endocrinology. PATIENT(S): Five thousand two hundred ninety-three pregnant women
      (721 with PCOS and 4,572 controls without PCOS). INTERVENTION(S): Literature
      search in the electronic databases MEDLINE, EMBASE, and CENTRAL, study of the
      references of all relevant trials or reviews, and manual search of the abstracts
      from the major meetings in the field of human reproduction. MAIN OUTCOME
      MEASURE(S): Gestational diabetes mellitus odds ratio. RESULT(S): Women with PCOS
      demonstrated a significantly higher risk for the development of GDM as compared
      with women without PCOS (odds ratio 2.89, 95% confidence interval [CI] 1.68
      4.98), yet with significant statistical heterogeneity (I(2) = 59.3%), durable to
      sensitivity analysis. In the subgroup of cohort studies, this finding remained
      robust (7.11, 95% CI 2.95-17.12), whereas in the subgroup of case-control
      studies, it did not (0.89, 95% CI 0.38-2.06). Metaregression modeling revealed a
      linear dependence of the outcome on study type and baseline risk (post hoc).
      CONCLUSION(S): Significant heterogeneity among studies and dependence of the
      outcome on study type make the higher risk of GDM in women with PCOS a
      questionable finding. The conduction of properly designed studies should precede
      any recommendation to pregnant women with PCOS in regard to the risk of GDM.

PMID- 18710714
TI  - Cervical ectopic pregnancy on the portio: conservative case management and
      clinical review.
AB  - OBJECTIVE: To present a case and management of an early ectopic pregnancy on the
      portio. DESIGN: Case study and literature review. SETTING: Hospital outpatient
      clinic. PATIENT(S): A 38-year-old woman who presented in the outpatient clinic
      with a 2-week history of painless acyclic vaginal bleeding. INTERVENTION(S):
      Excision of the ectopic pregnancy under local anesthesia after clinical
      examination, urine pregnancy test, and serum ss-hCG measurement. MAIN OUTCOME
      MEASURE(S): Conservative treatment options and preservation of patient's
      reproductive capacity. RESULT(S): Serum ss-hCG was raised. Complete excision of
      the ectopic lesion was performed without the need for administration of
      chemotherapeutic agents and curettage. Histology revealed fragments of the
      cervical wall with a layer of chorionic giant cells and one intact chorionic
      villi. CONCLUSION(S): Cervical pregnancy is a rare form of ectopic pregnancy. It
      can be associated with high morbidity and adverse consequences for future
      fertility, but spontaneous abortion is also possible. We present a case and
      successful management of an early ectopic pregnancy on the surface of the portio.

PMID- 18710715
TI  - Laparoscopic management of neural pelvic pain in women secondary to pelvic
      surgery.
AB  - OBJECTIVE: To report the impact of the laparoscopic approach to the pelvic nerves
      in the management of neural pelvic pain in women secondary to pelvic surgery.
      DESIGN: Clinical prospective study. SETTING: Department of Gynecology and
      Obstetrics, St. Elisabeth Hospital, Cologne/Germany. PATIENT(S): One hundred
      twenty consecutive patients with pelvic neural pain after failure of all previous
      surgical and medical treatments. INTERVENTION(S): Control of visceral pelvic pain
      was based on the LION procedure to the superior hypogastric plexus for permanent
      neuromodulation while pelvic somatic pain were primarily managed by laparoscopic
      nerve decompression. MAIN OUTCOME MEASURE(S): Comparison pre- and postoperatively
      of the pain situation with the visual analogue scale (VAS score) and consumption
      of analgesics. RESULT(S): Significant improvement was obtained in 65.5% of the
      patients with pelvic somatic pain (n = 113), whereas in seven patients with
      visceral pelvic pain, four of them reported on a significant reduction in the
      symptoms after neuromodulation of the superior hypogastric plexus. CONCLUSION(S):
      Laparoscopy is a unique method for diagnosis and therapeutic management of
      surgically damaged nerves and must be considered as a first-line option in the
      treatment of pelvic somatic pain, whereas in regard to the management of pelvic
      visceral pain, medical treatment remains first-line treatment.

PMID- 18710716
TI  - Persistence of androgenic effects on the production of proinflammatory cytokines
      by circulating antigen-presenting cells after withdrawal of testosterone
      treatment in aging type 2 diabetic men with partial androgen deficiency.
AB  - OBJECTIVE: To test the hypothesis that T treatment withdrawal could be associated
      with an enhancement of proinflammatory cytokine production by peripheral blood
      monocytes and dendritic cells. DESIGN: A prospective intervention study. SETTING:
      Tertiary university hospital. PATIENT(S): Thirteen type 2 diabetic men aged >55
      years with partial androgen deficiency and eight age-matched healthy men
      (controls). INTERVENTION(S): Analyses were performed before and 12 months after T
      replacement therapy and the results compared with those obtained for the same
      patients after a 3-month T withdrawal period. MAIN OUTCOME MEASURE(S):
      Distribution of circulating T, B, and natural killer lymphocytes, monocytes, and
      CD33(hi) myeloid, CD16+, and plasmacytoid dendritic cell subsets. Spontaneous and
      stimulated ex vivo production of inflammatory cytokines (interleukin-1beta,
      interleukin-6, and tumor necrosis factor-alpha) by circulating monocytes and
      dendritic cells, which represent the most potent antigen-presenting cells.
      RESULT(S): The reduction or complete abrogation of spontaneous ex vivo production
      of proinflammatory cytokines by monocytes and dendritic cells observed after 12
      months of T replacement therapy was maintained 3 months after T withdrawal.
      CONCLUSION(S): These are the first results showing that exogenous T treatment
      deprivation is not associated with an immunologic enhancement of proinflammatory
      cytokine production by antigen-presenting cells.

PMID- 18710717
TI  - Phospholipase C zeta undergoes dynamic changes in its pattern of localization in
      sperm during capacitation and the acrosome reaction.
AB  - OBJECTIVE: To evaluate the localization of phospholipase C zeta (PLC zeta) in non
      capacitated, capacitated, and ionophore-treated sperm. DESIGN: Phospholipase C
      zeta was cloned from the hamster, an important model organism for studying
      fertilization. Next, we used hamster and mouse models to investigate the
      localization of PLC zeta in non-capacitated and capacitated sperm and in sperm
      treated with ionophore to induce the acrosome reaction. SETTING: University
      laboratory. ANIMAL(S): Male mice and hamsters, 4-6 weeks old. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Phospholipase C zeta localization in non
      capacitated, capacitated, and ionophore-treated sperm. RESULT(S): Full-length
      hamster PLC zeta complementary DNA is 1953 base pairs in size, encoding an open
      reading frame of 651 amino acids, sharing 85% amino acid similarity with the
      mouse. Phospholipase C zeta was localized in acrosomal and post-acrosomal regions
      of sperm. The post-acrosomal localization, which became more evident after
      capacitation and was maintained after ionophore treatment, is in line with PLC
      zeta being the endogenous agent of egg activation. However, the acrosomal PLC
      zeta population, which was lost after ionophore treatment, suggests that PLC zeta
      could have other functions besides egg activation. CONCLUSION(S): Phospholipase C
      zeta is localized to acrosomal and post-acrosomal regions and undergoes dynamic
      changes during capacitation and the acrosome reaction, indicating a potential
      role regulating not only egg activation but other sperm functions.

PMID- 18710718
TI  - Bacterial endotoxin (LPS)-induced DNA damage in preimplanting embryonic and
      uterine cells inhibits implantation.
AB  - OBJECTIVE: To investigate lipopolysaccharide (LPS)-induced DNA damage in
      preimplanting embryonic and uterine cells during preimplantation period of
      pregnancy that may ultimately inhibit the process of implantation in mouse.
      DESIGN: Animal study. SETTING: Academic research environment. ANIMAL(S): Sixty
      four Park strain female mice. INTERVENTION(S): The "minimum dose" (MD) of LPS was
      injected intraperitoneally in the pregnant females on day 0.5 of pregnancy, and
      individual embryos and uterine cells were assessed by comet assay on days 1.5,
      2.5, 3.5, and 4.375 of the preimplantation period of pregnancy. MAIN OUTCOME
      MEASURE(S): Percentage of embryos and uterine cells with tail, mean comet tail
      length, percentage of fragmented DNA in tail. RESULT(S): Significantly higher
      numbers of embryos with higher mean comet tail length and percentage of
      fragmented DNA in tail were observed in the LPS-treated compared with control
      animals as the period of pregnancy approaches the stage of implantation. At the
      same time, DNA damage was also significantly higher in the uterine cells of LPS
      treated compared with control animals. CONCLUSION(S): The MD of LPS can induce
      DNA damage in the preimplantation-stage embryos and uterine cells, which causes
      poor embryonic development and improper preparation of uterine horns during the
      preimplantation period of pregnancy, which may ultimately inhibit the process of
      implantation in mouse.

PMID- 18710719
TI  - Letrozole administration during the luteal phase after ovarian stimulation
      impacts corpus luteum function: a randomized, placebo-controlled trial.
AB  - OBJECTIVE: To investigate the effect of letrozole-an oral aromatase inhibitor-on
      E(2), P, and LH levels when administered during the luteal phase after oocyte
      retrieval in IVF/intracytoplasmic sperm injection (ICSI) cycles. DESIGN:
      Prospective, randomized, placebo controlled trial. SETTING: University-affiliated
      private reproductive medicine center. PATIENT(S): Thirty oocyte donors undergoing
      standardized controlled ovarian hyperstimulation (COH) protocols.
      INTERVENTION(S): Patients were randomized after successful egg retrieval to
      receive either 2.5 mg of letrozole (Femara; Novartis, Barcelona, Spain) or a
      placebo (folic acid tablets). All donors were under intrauterine device (IUD)
      contraception. MAIN OUTCOME MEASURE(S): Serum E(2), P, and LH the day of hCG
      administration and days +4, +7 and +10 after ovum pick-up. RESULT(S): Donors had
      a comparable serum E(2) level on the day of hCG administration (1,858 vs. 2,143
      pg/mL). Interestingly, levels dramatically dropped 4 days after egg retrieval,
      reaching a statistically significant lower level in those receiving letrozole
      (279 vs. 1,586 pg/mL). Again, at the next time points serum E(2) levels were
      significantly lower (day +7: 240 vs. 855 pg/mL and day +10: 40 vs. 448 pg/mL). No
      significant differences were observed in P levels, but LH serum concentrations
      were lower in the control group on day +7 (0.18 vs. 0.02 mIU/mL and day +10 (0.40
      vs. 0.16 mIU/mL), when serum E(2) levels were higher. CONCLUSION(S): The
      administration of 2.5 mg of letrozole during the luteal phase has an impact on
      corpus luteum (CL) function. It reduces serum E(2) levels, which allows a faster
      recovery of LH concentration. This may be of interest not only for egg donors,
      but also in patients at high risk of ovarian hyperstimulation syndrome (OHSS) who
      freeze all their embryos or who cancel hCG administration to reduce the potential
      risk that high E(2) levels pose.

PMID- 18710720
TI  - Bowel preparations for capsule endoscopy: a comparison between simethicone and
      magnesium citrate.
AB  - BACKGROUND: Bowel preparation for capsule endoscopy (CE) has not been
      standardized. OBJECTIVE: This study aimed to compare CE images between patients
      prepared by simethicone and those prepared by magnesium citrate. DESIGN:
      Retrospective analysis of case series of our hospital from 2004 to 2007. SETTING:
      Single center. PATIENTS AND INTERVENTIONS: CE images of 75 patients receiving
      bowel preparation either by 200 mg of simethicone (n=39) or by 34 g of magnesium
      citrate (n=36) were retrospectively investigated. Grades of fluid transparency
      and mucosal invisibility by air bubbles and food residue were compared between
      the 2 preparations. Capsule transit time, frequency of positive findings, and
      interobserver variations between 2 observers were also investigated. MAIN OUTCOME
      MEASUREMENTS: Image quality and diagnostic yield of CE. RESULTS: Fluid
      transparency in the first and the third time segments of the small intestine was
      better in patients prepared by magnesium citrate than in those prepared by
      simethicone (P= .001 and P= .03, respectively). On the other hand, mucosal
      invisibility was not different in any part of the small intestine between the 2
      groups. Neither gastric transit time nor small-bowel transit time was different
      between the 2 groups. The diagnostic yield of CE correlated significantly with
      fluid transparency (P= .04), but it did not correlate with mucosal invisibility.
      LIMITATIONS: Single-center retrospective study. CONCLUSION: Magnesium citrate
      seems to be a recommended preparation for CE compared with simethicone. The fluid
      transparency, rather than the mucosal invisibility, may be a factor associated
      with the diagnostic yield of CE.

PMID- 18710721
TI  - Long-term followup of complete primary repair of exstrophy: the Seattle
      experience.
AB  - PURPOSE: Since 1989, we have used the complete primary repair of exstrophy
      surgical technique to reconstruct the genitourinary system of children born with
      the exstrophy-epispadias complex based on the assumption that this complex
      represents a malformation. We initially reported using this technique in 1999. We
      now report a longer term followup of this initial group as well as surgical
      outcomes in a larger group of children who have undergone this repair for classic
      bladder exstrophy. MATERIALS AND METHODS: Since 1989, we have prospectively
      followed 39 children who underwent the complete primary repair of exstrophy
      technique to construct classic bladder exstrophy. Median followup in the original
      group of patients that we reported in 1999 is 106 months. Median followup in the
      entire series is 58 months. RESULTS: Of boys and girls 4 years or older 74% have
      achieved daytime continence with volitional voiding. Of boys and girls 20% and
      43%, respectively, have achieved primary urinary continence without the need for
      bladder neck reconstruction. An additional 18% of boys and girls achieved
      continence with only bladder neck injection following complete primary repair of
      exstrophy. Complications developed in 7 of the 39 children (18%) in the entire
      series. CONCLUSIONS: Urinary continence has been consistently achieved with this
      form of exstrophy repair. Primary continence without the need for further
      reconstruction is possible. The results of this patient series have caused us to
      modify the complete primary repair of exstrophy technique in an effort to improve
      the rate of primary urinary continence.

PMID- 18710723
TI  - Urinomas associated with posterior urethral valves.
AB  - PURPOSE: We evaluated the incidence and clinical implications of urinomas in boys
      with posterior urethral valves. Our secondary aim was to evaluate the treatment
      modalities of urinomas. MATERIALS AND METHODS: We retrospectively reviewed the
      hospital data of 200 patients with posterior urethral valves treated between 1953
      and 2003. Documentation was sufficient in 196 cases to evaluate the presence of
      urinomas. A group of 69 patients with posterior urethral valves without urinoma
      served as controls. RESULTS: Of 196 patients 17 (9%) had urinoma. However, the
      incidence of urinoma increased to 15% after ultrasonography came into standard
      clinical use. Nine patients had perirenal urine collection, 6 had urinary ascites
      and 2 had urinothorax. At presentation median serum creatinine values were
      similar in patients with urinoma (145 mumol/l, range 54 to 431) and controls (126
      mumol/l, 19 to 593, p = 0.547). Creatinine decreased similarly in patients with
      and without urinoma after the obstruction was relieved. Vesicoureteral reflux was
      detected in 69% of the patients with urinoma and in 76% of the controls. Median
      split function on the side of the urinoma was 51% (range 38% to 70%) on
      (99m)technetium diethylenetetramine pentaacetic acid scintigraphy. During
      childhood end-stage renal failure developed in 4 of the 16 patients (25%) with
      urinoma and in 16 of the 69 controls (23%). CONCLUSIONS: The true incidence of
      urinomas is probably close to 15% in patients with posterior urethral valves.
      Renal function is similar in patients with posterior urethral valves with and
      without urinoma. In asymptomatic cases urinomas apparently do not require any
      specific treatment.

PMID- 18710724
TI  - Sonic Hedgehog mediator Gli2 regulates bladder mesenchymal patterning.
AB  - PURPOSE: Congenital bladder anomalies are a major challenge to pediatric
      urologists. Understanding the mechanism of bladder development is crucial for
      advancing patient treatment. Current evidence suggests that Shh (R&D Systems) is
      an epithelial signal regulating bladder development, although the mechanism of
      the regulation is still unclear. We examined the regulation of bladder
      mesenchymal development. MATERIALS AND METHODS: Mutation analysis,
      immunohistochemistry, immunoblot, in situ hybridization, and primary cell culture
      and transfection were performed. The mesenchyma proximal to the epithelium was
      defined as the inner zone and that distal to the epithelium was defined as the
      outer zone. RESULTS: We found that the Shh transcriptional factor Gli2 and the
      Shh target gene Bmp4 (R&D Systems) were expressed in the inner mesenchymal zone
      of the bladder, where active cell proliferation was observed. In Gli2(-/-)
      bladder primary mesenchymal cell cultures transfection with adenoviruses
      expressing DeltaNGli2, a constitutionally active form of Gli2, up-regulated Bmp4
      expression and promoted cell proliferation. In the outer mesenchymal zone, where
      Gli2 and Bmp4 expression was not detectable, smooth muscle alpha-actin was
      expressed. In Gli2(-/-) embryo bladders Bmp4 expression in the inner zone was
      lost and ectopic smooth muscle was detected in the inner mesenchymal zone.
      Exogenous Bmp4 (10 ng/ml) in primary smooth muscle cell culture repressed smooth
      muscle differentiation and repression was partially rescued by the Bmp4
      antagonist Noggin (R&D Systems) (300 ng/ml). CONCLUSIONS: Our data suggests that
      the Shh transcriptional factor Gli2 regulates radial patterning of the bladder
      mesenchyma.

PMID- 18710725
TI  - Renal apoptosis following carbon dioxide pneumoperitoneum in a rat model.
AB  - PURPOSE: Laparoscopically recruited kidneys regain normal function more slowly
      than laparotomy harvested organs for several possible reasons. We investigated
      the effects of CO(2) induced pneumoperitoneum on kidney function, as reflected by
      blood and urine creatinine levels, and its relation with renal cell apoptosis.
      MATERIALS AND METHODS: CO(2) pneumoperitoneum was established in anesthetized
      Wistar male rats that were randomly allocated at 6 per group into 1 of 6 groups
      with an intraperitoneal pressure of 0 (control), 5, 8, 12, 15 or 18 mm Hg.
      Pressure was maintained for 60 minutes in all groups. Three additional groups
      were subjected to 30-minute pneumoperitoneum at 0, 12 and 18 mm Hg, respectively.
      The rats were kept alive for the ensuing 24 hours, after which blood and urine
      creatinine were analyzed and the abdominal organs were harvested. Various areas
      of the organs were analyzed for apoptotic cells using the TUNEL method. Cells
      were randomly counted in 10 eyeshots in 3 sections each using an ocular
      micrometer. RESULTS: Creatinine levels in blood and urine changed as pressure and
      pneumoperitoneum duration progressed. Isolated TUNEL positive nuclei were
      detected in the outer medulla and the cortex of control kidneys. There was a
      significantly higher number of TUNEL positive nuclei in the cortex and the
      medulla of all pressurized kidneys (p <0.05), which increased in parallel with
      increasing intraperitoneal pressure and pneumoperitoneum exposure time.
      CONCLUSIONS: The CO(2) pneumoperitoneum gradient and its duration affect renal
      function and induce apoptosis. This could be a mechanism involved in renal
      delayed graft dysfunction in recipients of laparoscopically harvested kidneys.

PMID- 18710726
TI  - The relevance of urodynamic studies for Urge syndrome and dysfunctional voiding:
      a multicenter controlled trial in children.
AB  - PURPOSE: The objective of this study was to compare prospectively, in urge
      syndrome and dysfunctional voiding, clinical patterns with urodynamic patterns,
      to assess changes in urodynamic patterns after treatment, and to correlate
      urodynamic patterns and parameters with treatment outcome. MATERIALS AND METHODS:
      In the European Bladder Dysfunction Study 97 children with clinically diagnosed
      urge syndrome received standard treatment, to which was randomly added placebo,
      oxybutynin or bladder training with online feedback. In a separate branch 105
      children with clinically diagnosed dysfunctional voiding were randomly allocated
      to standard treatment or standard treatment plus pelvic floor training with
      online feedback. In all children urodynamic studies were performed before and
      immediately after treatment. RESULTS: In urge syndrome detrusor overactivity was
      present in 33% of cases before and 27% after treatment (of which 65% were de
      novo). Detrusor overactivity did not correlate with treatment outcome. In
      dysfunctional voiding increased pelvic floor activity during voiding, which was
      present in 67% of cases before and 56% after treatment (of which 45% were de
      novo), did not correlate with treatment outcome. In urge syndrome as well as in
      dysfunctional voiding neither maximum detrusor pressure during voiding,
      cystometric bladder capacity, bladder compliance nor free flow patterns
      correlated with treatment outcome. CONCLUSIONS: Neither detrusor overactivity nor
      increased pelvic floor activity during voiding correlated with treatment outcome.
      Standard treatment could be the first choice in urge syndrome as well as in
      dysfunctional voiding, reserving urodynamic studies for patients in whom this
      first approach fails.

PMID- 18710728
TI  - Long-term followup and comparison between genotype and phenotype in 29 cases of
      complete androgen insensitivity syndrome.
AB  - PURPOSE: Diagnosis and management of the complete androgen insensitivity syndrome
      have dramatically changed in the last few decades, with earlier diagnosis and the
      development of molecular biology. Some phenotypic features such as development of
      wolffian and mullerian remnants have been suggested to be an index of subtle
      residual androgen activity. Variations of these features clearly exist among
      patients and may influence treatment. Our aim was to assess the safety of keeping
      gonads in place for spontaneous puberty in a cohort of patients with genetically
      proved complete androgen insensitivity syndrome. In parallel to the risks of
      virilization at puberty and gonadal tumor some additional features, such as need
      for vaginal surgery, were investigated. MATERIALS AND METHODS: We studied the
      genotype, phenotype, anatomy of the internal and external genitalia, and clinical
      outcome of 29 cases of complete androgen insensitivity syndrome, managed by the
      same team from diagnosis (frequently in early childhood) to adulthood. RESULTS:
      All patients had a complete female phenotype. A total of 19 different mutations
      (including 7 unreported) were found. Each family presented with a different
      mutation. No somatic mosaicism was detected. Vas deferens and epididymis were
      found in all types of mutations (missense, nonsense and frameshift). Of the
      patients 23 were postpubertal (19 spontaneously). No postpubertal virilization
      occurred. Only 1 carcinoma in situ was detected (postpubertally). Vaginal surgery
      was rarely necessary. CONCLUSIONS: Our data advocate for keeping the gonads in
      the complete androgen insensitivity syndrome, at least until completion of
      spontaneous puberty. The risk of virilization at puberty should be ruled out for
      each androgen receptor mutation before management decisions and genetic
      counseling. Vaginal surgery should not be indicated as first line treatment.

PMID- 18710733
TI  - Unilateral vesicoureteral reflux and history of contralateral vesicoureteral
      reflux warranting routine bilateral endoscopic correction.
AB  - PURPOSE: It has been shown that the incidence of de novo vesicoureteral reflux
      following unilateral endoscopic correction is low and does not justify
      prophylactic injection into the nonrefluxing ureter. We analyzed whether we
      should routinely treat each ureter in patients with a history of bilateral
      vesicoureteral reflux in whom reflux previously disappeared spontaneously on 1
      side. MATERIALS AND METHODS: Between 1991 and 2005, 458 children underwent
      endoscopic correction of unilateral vesicoureteral reflux. Of the children 15
      with bilateral vesicoureteral reflux at the beginning of followup showed
      spontaneous reflux resolution on 1 side. Resolved reflux was grade II to IV in 5,
      8 and 2 children, respectively. Mean time to reflux resolution was 3.3 years
      (range 2 to 5). Reflux corrected endoscopically was grade II to IV in 1, 6 and 8
      children, respectively. All children were female and age at endoscopic correction
      was 2 to 16 years. None of the children had voiding dysfunction at the time of
      injection. Injection was performed routinely only into the refluxing ureter.
      Configuration of the orifice of the ureter with resolved vesicoureteral reflux
      was recorded at injection. RESULTS: Vesicoureteral reflux was corrected in all
      except 1 ureter, in which reflux was downgraded to grade I. The configuration of
      the orifice of the ureter with resolved reflux was normal in all children. Of the
      15 children 14 (93%) showed recurrent vesicoureteral reflux in previously
      resolved ureters. Recurrent reflux grade was I to III in 1 (7.1%), 6 (42.8%) and
      7 children (50%), respectively. All children required endoscopic correction on
      the side of recurrence due to high grade reflux in 7 and breakthrough urinary
      tract infection in the remaining 7. In 2 cases (14.2%) renal scan revealed new
      renal scarring. CONCLUSIONS: There is a high incidence of recurrent
      vesicoureteral reflux in previously resolved ureters following endoscopic
      correction on the contralateral side. Therefore, we recommend routine injection
      of the 2 ureters in patients with a history of bilateral vesicoureteral reflux.

PMID- 18710734
TI  - Urethroplasty in patients with kidney and pancreas transplants.
AB  - PURPOSE: In patients with solid organ transplants urethral strictures may develop
      from repeat catheterization, recurrent urinary tract infection or chronic
      irritation of the urethral mucosa secondary to contact with pancreatic enzymes.
      We describe surgical outcomes in patients with kidney and kidney-pancreas
      transplants after urethral reconstruction for stricture or fistula disease.
      MATERIALS AND METHODS: Ten males underwent urethroplasty for urethral stricture
      (9) or urethral fistula (1) disease after kidney or kidney-pancreas
      transplantation. Median patient age was 41.5 years (range 25 to 56) and average
      time from transplantation was 9 years (range 1 to 14). Four patients underwent
      bulbar urethroplasty with buccal mucosa, 3 underwent stricture excision and
      primary anastomosis of the bulbar urethra, 2 underwent penile urethroplasty with
      graft tissue and 1 underwent bulbar urethrocutaneous fistula repair. RESULTS: The
      etiology of stricture disease was pancreatic enzyme induced stricture in 40% of
      cases, catheter trauma in 40% and unknown in 20%. Nine of 10 patients (90%) were
      free of symptoms and recurrence at a median followup of 32.5 months (range 4 to
      83). One patient who required cystoscopy and dilation for a bulbar urethral
      recurrence is currently disease-free. Postoperative morbidity included urinary
      tract infection and a perineal hematoma requiring transfusion. CONCLUSIONS: We
      describe the outcomes of urethral reconstruction in patients with kidney and
      kidney-pancreas transplantation. As in men with normal native kidney and pancreas
      function, urethroplasty appears to be safe and effective in this cohort. Long
      term outcome data are needed to confirm these findings.

PMID- 18710737
TI  - Office based vasectomy can be performed by supervised urological residents with
      patient pain and morbidity comparable to those of a staff surgeon procedure.
AB  - PURPOSE: Although it is routinely performed in the ambulatory setting, vasectomy
      is an intricate surgical procedure with the potential for significant pain and
      morbidity. We determined from our prospective, institutional review board
      approved database whether vasectomy pain was affected by whether a staff surgeon
      or resident was the primary surgeon on the case. MATERIALS AND METHODS: One staff
      surgeon and 14 residents in training year 2, 3 or 5 performed bilateral
      percutaneous no-scalpel vasectomy. Men scheduled to undergo vasectomy were
      assigned to the staff urologist (134) or to a resident (133) as the primary
      surgeon. The staff surgeon demonstrated the first vasectomy each month when a new
      resident rotated on service and all residents were directly assisted by the staff
      surgeon. Pain associated with each side of the bilateral vasectomy was assessed
      with a 0 to 100 mm visual analog scale. RESULTS: The average visual analog scale
      score of the 2 sides was 19.5 in patients in the staff cohort and 21.8 in those
      in the resident cohort. Although mean scores were slightly lower when vasectomy
      was performed by the staff surgeon, the difference between the staff surgeon and
      residents was neither statistically nor clinically significant. Furthermore,
      there were no significant differences in visual analog scale scores among
      residents of different training years. CONCLUSIONS: Office based vasectomy can be
      performed by residents under staff supervision with pain comparable to that of
      the procedure performed by a staff urologist. Urological resident training can be
      accomplished without compromising high standards of care.

PMID- 18710738
TI  - Profile of the veterans affairs urologist: results from a national survey.
AB  - PURPOSE: The Veterans Health Administration has multiple employment arrangements
      for its physician staff. Urological care to veterans is provided by urologists
      who work in the Veterans Affairs system under 1 arrangement, including full-time
      Veterans Affairs, contract Veterans Affairs, part-time Veterans Affairs and fee
      for service. We assessed the similarities and differences of these employment
      arrangements, while considering factors such as race, gender, professional
      activities and salary. MATERIALS AND METHODS: A database was created of all
      urologists who provide care at Veterans Affairs Medical Centers across the United
      States regardless of the employment arrangement. A 14-item survey was sent to
      these 305 urologists. Participants were required to have finished residency
      training and be employed by the Veterans Affairs on a full-time, part-time,
      contract or fee for service basis. RESULTS: A total of 118 surveys were completed
      for a 39% response rate. Compared to full-time urologists contract urologists
      were younger (p = 0.02), earned higher annual wages (p = 0.01), worked longer
      hours per week (p = 0.001), and spent more hours on direct patient care (p =
      0.001) and teaching residents (p = 0.03), although they spent the same number of
      hours on research and administrative duties. CONCLUSIONS: The practice
      environment of the contract urologist in the Veterans Affairs system is
      comparable in many ways to that of the full-time employee. However, the tendency
      of many contract urologists to be employed in a separate practice setting has led
      to higher incomes and longer work hours.

PMID- 18710741
TI  - Outcome analysis of mini-ureteroneocystostomy versus dextranomer/hyaluronic acid
      copolymer injection for unilateral vesicoureteral reflux.
AB  - PURPOSE: Injecting dextranomer/hyaluronic acid copolymer has gained popularity as
      first line treatment for vesicoureteral reflux. However, ureteroneocystostomy has
      typically been more successful than endoscopic treatments. We evaluated the
      outcome of dextranomer/hyaluronic acid copolymer injection vs that of
      extravesical ureteroneocystostomy via a 2 cm inguinal incision (mini
      ureteroneocystostomy) for unilateral vesicoureteral reflux. MATERIALS AND
      METHODS: The records were analyzed of all patients from 2003 to 2007 with
      unilateral vesicoureteral reflux who underwent mini-ureteroneocystostomy or
      dextranomer/hyaluronic acid copolymer injection. Mini-ureteroneocystostomy was
      performed via a 2 cm inguinal incision. Of the injections 66% were delivered via
      an intraureteral tunnel technique. Statistical analysis was done to compare
      differences in clinical features and success rates. All p values were 2-sided
      with significance at p <0.05. RESULTS: From 2003 to 2007, 99 children underwent
      operative repair of unilateral vesicoureteral reflux, including 42 via
      dextranomer/hyaluronic acid copolymer injection and 57 via mini
      ureteroneocystostomy. There were no significant differences between the groups in
      terms of preoperative clinical or anatomical variables except for higher
      preoperative reflux grade in the mini-ureteroneocystostomy cohort (p <0.001).
      Patients undergoing mini-ureteroneocystostomy were more likely to be cured (100%
      vs 78%, p = 0.001). De novo contralateral vesicoureteral reflux occurred in the 2
      cohorts to a similar degree (p = 0.15). The injection cohort was more likely to
      be discharged home on an outpatient basis (100% vs 82%, p = 0.002). No
      complications occurred in the dextranomer/hyaluronic acid copolymer cohort, while
      2 children required intervention for complications after mini
      ureteroneocystostomy. CONCLUSIONS: This study details that the 2 procedures may
      be successfully performed in the outpatient setting, and yet even for more
      advanced vesicoureteral reflux mini-ureteroneocystostomy achieves greater overall
      success. This procedure has become our standard of care for unilateral
      vesicoureteral reflux.

PMID- 18710743
TI  - Testosterone recovery after prolonged androgen suppression in patients with
      prostate cancer.
AB  - PURPOSE: We prospectively examined the extent and timing of testosterone recovery
      in patients with prostate cancer treated with 2 years of androgen suppression.
      MATERIALS AND METHODS: A total of 153 patients with pT3N0M0 prostate cancer or
      positive margins after radical prostatectomy, or with prostate specific antigen
      relapse were treated with radiation to the prostate bed plus 2 years of androgen
      suppression as per a phase II study. Androgen suppression consisted of nilutamide
      for 4 weeks plus busereline acetate bimonthly for 2 years. Serum testosterone was
      measured at baseline, every 4 months during androgen suppression and every 6
      months after androgen suppression during followup. Testosterone recovery to
      supracastrate levels, and to baseline and/or normal levels was estimated using
      Kaplan-Meier methods. Prognostic factors for testosterone recovery were examined.
      RESULTS: A total of 121 patients who completed 2 years of androgen suppression
      and 20 patients who received shorter durations of androgen suppression (median 16
      months) were available for testosterone recovery analysis. Median followup after
      finishing androgen suppression was 38.9 months. All patients achieved castrate
      levels on androgen suppression. At 36 months after completion of androgen
      suppression 93.2% and 71.5% had recovery to supracastrate (median time 12.7
      months), and to baseline and/or normal testosterone levels (median time 22.3
      months), respectively. On multivariate analysis younger age (younger than 60
      years, p = 0.0006) and shorter androgen suppression duration (less than 2 years,
      p = 0.028) were prognostic for faster recovery to baseline and/or normal
      testosterone levels after adjusting for baseline testosterone levels (p = 0.447).
      CONCLUSIONS: Testosterone recovery after prolonged androgen suppression is
      protracted. Older age and longer duration of androgen suppression result in
      significantly longer recovery times to baseline and/or normal testosterone
      levels.

PMID- 18710745
TI  - Evaluating the evidence: statistical methods in randomized controlled trials in
      the urological literature.
AB  - PURPOSE: Randomized controlled trials potentially provide the highest level of
      evidence to inform clinical decision making. Appropriate use of statistical
      methods is a critical aspect of all clinical research, including randomized
      controlled trials. We report the first formal evaluation to our knowledge of the
      statistical methods of randomized controlled trials published in the urological
      literature in 1996 and 2004. MATERIALS AND METHODS: All human subjects randomized
      controlled trials published in 4 leading urology journals in 1996 and 2004 were
      identified for formal review. A standardized evaluation form was developed based
      on the Consolidated Standards of Reporting Trials statement. Each article was
      evaluated by 2 independent reviewers with formal training in research design and
      biostatistics who were blinded to study authors and institution. Discrepancies
      were settled by consensus. RESULTS: A total of 152 randomized controlled trials
      were reviewed (65 in 1996, 87 in 2004). The median sample size (IQR) per arm of
      parallel design randomized controlled trials published in 1996 and 2004 was 36
      (11, 96) and 50 (26, 134) study subjects, respectively (p = 0.157). Sample size
      justifications were provided by 19% of studies in 1996 and 47% of studies in 2004
      (p = 0.001). Of randomized controlled trials 16 (25%) vs 32 (37%) identified a
      single primary outcome variable (p = 0.110). Effect size estimates for primary or
      secondary outcome variables were provided by 5% vs 13% (p = 0.090) and the
      precision of the effect was detailed by 5% vs 10% of randomized controlled trials
      (p = 0.195). CONCLUSIONS: This formal review suggests that statistical analysis
      in urological randomized controlled trials has improved. However, considerable
      deficiencies remain. Ongoing education in applied statistics may further improve
      urological randomized controlled trial reporting.

PMID- 18710746
TI  - Is varicocele associated with underlying venous abnormalities? Varicocele and the
      prostatic venous plexus.
AB  - PURPOSE: We examined the pampiniform plexus and prostatic venous plexus using
      color Doppler ultrasonography and evaluated the relationship between varicocele
      and the prostatic venous plexus. MATERIALS AND METHODS: This study included 209
      men with a mean age of 35.3 years, of whom 68 had no varicoceles, 94 had a
      unilateral varicocele and 47 had bilateral varicoceles based on scrotal color
      Doppler ultrasonography. The diameter of the pampiniform plexus and prostatic
      venous plexus was measured using scrotal and transperineal ultrasonography,
      respectively. Peak retrograde and antegrade flow velocity of the prostatic venous
      plexus was measured by transperineal color Doppler ultrasonography. RESULTS: Mean
      diameter, and peak and antegrade flow velocity of the prostatic venous plexus
      were greater in men with bilateral varicoceles than in those with a unilateral
      varicocele and in those without a varicocele (p <0.01). Moreover, men with a
      unilateral varicocele had a greater mean peak antegrade flow velocity than those
      without a varicocele (p <0.05). However, mean diameter and peak retrograde flow
      velocity were not different in men with a unilateral varicocele and those without
      a varicocele. In 10 men with a left clinical varicocele mean diameter, and peak
      retrograde and antegrade flow velocity of the prostatic venous plexus did not
      differ before vs after varicocele repair. In all men the diameter of the
      prostatic venous plexus positively correlated with the diameter of the right and
      left pampiniform plexus (p <0.0001). CONCLUSIONS: Varicocele, especially
      bilateral varicoceles, may be associated with underlying venous abnormalities.

PMID- 18710749
TI  - A novel technique for creating solid renal pseudotumors and renal vein-inferior
      vena caval pseudothrombus in a porcine and cadaveric model.
AB  - PURPOSE: We developed a simple means to replicate kidney tumors in an animal and
      cadaver model that could be used to create pseudotumors of different sizes and
      locations for use in surgical training. MATERIALS AND METHODS: Various substances
      were injected ex vivo into the parenchyma of porcine kidneys to identify an
      optimal pseudotumor model. Renal pseudotumors were created percutaneously and
      endoscopically using 8 live pigs and a human cadaver model. A renal vein
      pseudothrombus porcine model was also created by injecting pseudothrombus
      material into the renal vein after renal hilar clamping. Procedures performed on
      pseudotumors included robotic partial nephrectomy, percutaneous biopsy and
      robotic nephrectomy with renal vein thrombectomy. All specimens were analyzed
      after resection. RESULTS: The most ideal pseudotumor models were created from a
      mixture of gelatin, Metamucil and methylene blue (metagel) or from Kromopan
      hydrocolloid. We created 33 tumors 0.5 to 3.5 cm in size (mean 2.8). All tumors
      were a solid palpable mass on gross examination and ultrasonography revealed
      clearly visible hyperechoic lesions in 30 of 33. A renal vein tumor
      pseudothrombus model was successfully created in 3 pigs. We successfully
      performed robotic excision of pseudotumors, including partial nephrectomy for 16
      and radical nephrectomy with renal vein thrombectomy for 3. Percutaneous needle
      core biopsy under ultrasound guidance was also successfully performed.
      CONCLUSIONS: We describe what is to our knowledge a novel technique of creating
      solid renal tumors and tumor thrombi that can be used for training in minimally
      invasive kidney surgery.

PMID- 18710748
TI  - Kinetics of serum androgen normalization and factors associated with testosterone
      reserve after limited androgen deprivation therapy for nonmetastatic prostate
      cancer.
AB  - PURPOSE: Groups have investigated time to testosterone recovery in patients who
      have undergone androgen deprivation therapy, usually by measuring androgen every
      3 months, with varying results. To our knowledge this represents the largest
      study using monthly testosterone and dihydroxytestosterone measurement to
      evaluate the kinetics of androgen recovery following limited androgen deprivation
      therapy. MATERIALS AND METHODS: Monthly serum androgen levels were analyzed
      following 2, 6-month cycles of gonadotropin-releasing hormone agonist therapy as
      part of a randomized, placebo controlled study of the role of thalidomide in
      delaying time to prostate specific androgen progression. RESULTS: By the Kaplan
      Meier method the median time to testosterone normalization in cycles 1 vs 2 was
      15.4 vs 18.3 weeks with similar dihydroxytestosterone recovery times. Neither on
      study prostate specific antigen, Gleason score nor thalidomide treatment had a
      significant impact on time to testosterone normalization. However, in cycle 1 men
      with low baseline dihydroxytestosterone and those who were more than 67 years old
      had significantly longer time to T normalization on Cox model analysis.
      Additionally, in cycle 2 patients with prior local radiation therapy had longer
      time to testosterone normalization, although this was no longer significant on
      Cox model analysis. Cox model analysis in cycle 2 showed that low baseline
      dihydroxytestosterone and testosterone, low testosterone nadir and white race
      were associated with longer time to testosterone normalization. CONCLUSIONS:
      Findings of delayed testosterone recovery may be useful for designing and
      analyzing clinical trials of limited androgen deprivation therapy and for
      estimating the duration of treatment associated side effects in patients
      undergoing limited androgen deprivation therapy.

PMID- 18710753
TI  - Intra-orifice versus hydrodistention implantation technique in
      dextranomer/hyaluronic acid injection for vesicoureteral reflux.
AB  - PURPOSE: Original implantation procedures used dextranomer/hyaluronic acid to
      create a volcano-like mound at the orifice. Subsequently the hydrodistention
      implantation technique was described to coapt the intramural ureteral wall with
      less emphasis on achieving a mound at the orifice and it was reported to be
      associated with improved outcomes. We compared the results of intra-orifice
      injection to establish a mound vs the hydrodistention implantation technique.
      MATERIALS AND METHODS: Univariate and multivariate logistic regression analysis
      was used to compare results in 96 ureters undergoing intra-orifice injection vs
      52 undergoing the hydrodistention implantation technique. We evaluated patient
      gender and age, reflux grade, injection technique, injected volume and the number
      of injection sites. RESULTS: Successful reflux resolution was achieved in 124
      ureters (84%) with a single implantation, including 83 (86.5%) with intra-orifice
      injection and 41 (79%) with HIT (p = 0.23). Mean injected volume was
      significantly increased for the hydrodistention implantation technique vs intra
      orifice injection (0.68 vs 0.51 cc, p = 0.002). Univariate analysis showed that
      female gender, older age, reflux grade and number of injection sites were
      associated with success. On multivariate analysis only reflux grade remained
      significant. CONCLUSIONS: Despite using an increased volume of
      dextranomer/hyaluronic acid to coapt the intramural ureter and orifice, the
      hydrodistention implantation technique did not improve results over those of
      intra-orifice injection with a lesser implant volume.

PMID- 18710756
TI  - Learning from the learning curve: factors associated with successful endoscopic
      correction of vesicoureteral reflux using dextranomer/hyaluronic acid copolymer.
AB  - PURPOSE: Conflicting reports exist regarding the parameters guiding successful
      correction of vesicoureteral reflux using dextranomer/hyaluronic acid copolymer.
      We performed logistic regression analysis to evaluate the effect of injected
      volume while adjusting for other factors potentially associated with success
      following dextranomer/hyaluronic acid copolymer injection. MATERIALS AND METHODS:
      Between July 2003 and June 2006, 126 consecutive patients (34 boys and 92 girls)
      with a mean +/- SD age of 6.5 +/- 3.7 years with primary vesicoureteral reflux
      (196 refluxing ureters) underwent injection for febrile urinary tract infections.
      Success was defined as complete reflux resolution. Age, gender, laterality,
      preoperative vesicoureteral reflux grade, surgeon experience,
      dextranomer/hyaluronic acid copolymer volume, time to surgery from initial
      presentation and preoperative treatment for lower urinary tract symptoms were
      analyzed. RESULTS: Vesicoureteral reflux grade was I to V in 7 (3.5%), 53 (27%),
      91 (46.4%), 30 (15.3%) and 15 renal units (7.6%), respectively. The success rate
      after 1 injection was 50% by patient and 59.2% by ureter. Mean injected volume
      was 0.9 +/- 0.27 ml in those who had a successful injection vs 0.67 +/- 0.24 ml
      in those in whom injection failed (p <0.001). The success rate after 1 injection
      was 78.9% using 0.8 ml or greater dextranomer/hyaluronic acid copolymer compared
      to 31.7% with less than 0.8 ml. Multivariate analysis confirmed that higher
      dextranomer/hyaluronic acid copolymer volume (p = 0.001), lower preoperative
      grade (p = 0.013), surgeon experience (p = 0.025) and treatment for lower urinary
      tract symptoms (p = 0.009) were associated with successful correction of
      vesicoureteral reflux. CONCLUSIONS: Our analysis strengthens the previously
      reported association of surgeon experience and vesicoureteral reflux grade with
      successful endoscopic vesicoureteral reflux correction. The data also revealed an
      association between injected volume and vesicoureteral reflux correction even
      while controlling for other variables, highlighting its importance as a true
      success modifier.

PMID- 18710759
TI  - Urethral reconstruction using oral keratinocyte seeded bladder acellular matrix
      grafts.
AB  - PURPOSE: We investigated the feasibility of urethral reconstruction using oral
      keratinocyte seeded bladder acellular matrix grafts. MATERIALS AND METHODS:
      Autologous oral keratinocytes were isolated, expanded and seeded onto bladder
      acellular matrix grafts to obtain a tissue engineered mucosa. The tissue
      engineered mucosa was assessed using morphology and scanning electron microscopy.
      In 24 male rabbits a ventral urethral mucosal defect was created. Urethroplasty
      was performed with autogenic oral keratinocyte seeded bladder acellular matrix
      grafts in 12 rabbits in the experimental group or with bladder acellular matrix
      grafts with no cell seeding in 12 in the control group. Retrograde urethrography
      was performed 1, 2 and 6 months after grafting. The urethral grafts were analyzed
      grossly and histologically. RESULTS: Oral keratinocytes had good biocompatibility
      with bladder acellular matrix grafts. Rabbits implanted with oral keratinocyte
      seeded bladder acellular matrix grafts voided without difficulty. Retrograde
      urethrography revealed no sign of strictures at 1, 2 and 6 months. In the control
      group the urethra with repaired defects was accompanied by strictures.
      Histological examination showed that grafts seeded with oral keratinocytes formed
      a 1-layer structure by 1 month, and at 2 and 6 months the keratinocytes had
      formed multiple layers. There was an evident margin between graft oral
      keratinocytes and host epithelium. The oral keratinocytes at basilar layers of
      the grafts expressed P63, as shown by immunocytochemistry. In the control group
      histopathological evaluation revealed that no 1-layer or stratified epithelium
      cells had developed at the repaired defect sites, whereas an inflammatory
      reaction was found in 2 rabbits. CONCLUSIONS: Oral keratinocytes had good
      biocompatibility with bladder acellular matrix grafts. Urethral reconstruction
      with these grafts was better than with bladder acellular matrix grafts alone.

PMID- 18710758
TI  - Superficial genitourinary abscesses in children: emergence of methicillin
      resistant Staphylococcus aureus.
AB  - PURPOSE: The prevalence of methicillin resistant Staphylococcus aureus is
      increasing. However, little is known about methicillin resistant S. aureus in the
      genitourinary tract, particularly in children. We assessed the incidence of
      pediatric genitourinary methicillin resistant S. aureus superficial abscess
      requiring surgical intervention. MATERIALS AND METHODS: We reviewed the records
      of all children undergoing surgical debridement of superficial abscess at a
      single institution between 1995 and 2007. We assessed surgical site, organism
      identity, patient comorbidity, methicillin resistant S. aureus risk factors,
      number of procedures and patient outcome. RESULTS: Surgical debridement of a
      superficial genitourinary abscess was performed in 60 children. Patient age
      ranged from 29 days to 17 years (median 3 years). A single debridement was
      generally curative, with only 5 patients (8.3%) requiring more than 1 procedure.
      One patient (1.7%) died of sepsis postoperatively due to Pseudomonas infection.
      One patient had myelomeningocele, 1 had undergone renal transplant and 2 were
      undergoing chemotherapy at the time of debridement. None of these 3 patients had
      a methicillin resistant S. aureus infection. Methicillin resistant S. aureus was
      more common in the groin/genitalia and less common in the perineum (p = 0.007).
      The incidence of methicillin resistant S. aureus increased during the study
      period, accounting for none of 40 infections between 1995 and 2003, and 8 of 20
      (40%) from 2004 to 2007 (p <0.001). CONCLUSIONS: Methicillin resistant S. aureus
      has become the predominant organism causing pediatric superficial genitourinary
      abscesses at our institution, accounting for three-quarters of all surgically
      managed infections in the last 2 years. Methicillin resistant S. aureus was more
      common at the groin and genitalia. One debridement was generally curative, and
      patient morbidity was low with aggressive treatment.

PMID- 18710760
TI  - Hybrid augmented reality simulator: preliminary construct validation of
      laparoscopic smoothness in a urology residency program.
AB  - PURPOSE: We examined the usefulness, reliability and applicability of the
      smoothness metric of the ProMIS hybrid simulator (Haptica, Dublin, Ireland) for a
      urology residency program. MATERIALS AND METHODS: A total of 15 urology residents
      divided into junior and senior cohorts were followed prospectively for 6 training
      sessions. Validated McGill Inanimate System for Training and Evaluation of
      Laparoscopic Skills (MISTELS) laparoscopic tasks were used. The ProMIS hybrid
      simulator smoothness parameter, a unit-free metric of movement efficiency, was
      recorded using 3-dimensional visual tracking technology. Results were compared
      between cohorts at the midpoint and end of the defined training sessions. End of
      study junior means were also retrospectively compared to senior mid training
      means. Statistical significance was determined using the Mann-Whitney U test
      (alpha = 0.05). RESULTS: Statistically significant differences between 8 junior
      and 7 senior cohorts were measured in all MISTELS tasks. A statistically
      significant performance variation was also detected at the mid and end testing
      times. When juniors and seniors were compared between sessions 1 and 3, and 4 and
      6, statistically significant performance improvements were noted. Lastly,
      statistical differences were also maintained when mid session senior means were
      compared to end of session junior means. A 38% improvement in task completion in
      the senior cohort as well as a 10-fold decrease in variance was observed compared
      to a 12% improvement in juniors, indicating greater efficiency of movement in
      seniors. CONCLUSIONS: The laparoscopic smoothness metric in the hybrid simulator
      demonstrated construct validity by effectively differentiating between
      experienced and novice urology residents using validated MISTELS tasks. The
      outcome suggests that the hybrid simulator smoothness metric is a valuable asset
      in residency programs for preparatory training for live operative experience,
      allowing improved trainee assessment.

PMID- 18710761
TI  - Prostate screening in patients with 46,XY disorders of sex development--is it
      necessary?
AB  - PURPOSE: We used current methods of screening for prostate cancer, digital rectal
      examination and serum prostate specific antigen as an initial assessment of risk
      in a young group of adult 46,XY patients affected by disorders of sex
      development. MATERIALS AND METHODS: Adult intersex patients older than 21 years,
      under long-term followup at the Pediatric Endocrinology Clinic of the Johns
      Hopkins Hospital, with a diagnosis of male psuedohermaphroditism and raised as
      male or female were included in analysis. After written consent all participants
      underwent digital rectal examination and blood sampling for prostate specific
      antigen and testosterone measurements. RESULTS: Prostate specific antigen values
      were available for analysis in 26 patients. Diagnoses included micropenis (8),
      complete androgen insensitivity syndrome (3), partial androgen insensitivity
      syndrome (9) and mixed gonadal dysgenesis (6). Of the 26 patients 9 had been
      raised as female (complete androgen insensitivity syndrome in 3, partial androgen
      insensitivity syndrome in 3, micropenis in 2 and mixed gonadal dysgenesis in 1).
      Mean patient age was 38 years (range 24 to 57). Serum prostate specific antigen
      was less than 0.1 ng/ml in 18 patients including the 9 reared as female. The
      remaining 8 patients had a prostate specific antigen of 0.1 to 0.9 ng/ml, were
      reared as male and had a mean age of 39.6 years (range 33 to 44). The diagnoses
      in this group consisted of micropenis (4), partial androgen insensitivity
      syndrome (2) and mixed gonadal dysgenesis (2). All patients had a palpable, small
      prostate gland with no abnormalities noted on digital rectal examination.
      CONCLUSIONS: This study found measurable prostate specific antigen in a subset of
      male intersex patients that were comparable to controls matched for age and race.
      We recommend that patients with 46,XY disorder of sex development, reared as
      male, be screened for prostate cancer in a manner similar to men not affected by
      disorder of sex development.

PMID- 18710762
TI  - Febrile urinary tract infections in children with an early negative voiding
      cystourethrogram after treatment of vesicoureteral reflux with
      dextranomer/hyaluronic acid.
AB  - PURPOSE: Children in whom nonsurgical management for vesicoureteral reflux fails
      are considered candidates for surgical intervention. An option is endoscopic
      treatment with Deflux(R). We reviewed our experience with febrile urinary tract
      infections in children following initial successful treatment of vesicoureteral
      reflux with Deflux and identified factors predictive of post-Deflux urinary tract
      infections. We also analyzed the incidence of delayed vesicoureteral reflux
      recurrence in these patients. MATERIALS AND METHODS: We performed a retrospective
      chart review of all children from 2002 to 2006 diagnosed with grades I to IV
      vesicoureteral reflux who were treated with Deflux and who had a negative initial
      followup voiding cystourethrogram at 2 to 5 months. Patients were categorized
      into post-Deflux infection and infection-free groups. Predictive factors,
      including the number of preoperative febrile urinary tract infections,
      dysfunctional elimination and renal cortical defects on dimercapto-succinic acid
      scan, were analyzed and compared. RESULTS: Of the patients 45 met all study
      inclusion and exclusion criteria. A total of 12 patients (27%) who were diagnosed
      with a culture documented febrile urinary tract infection were categorized into
      the infection group. Of 12 children in the post-Deflux infection group 11 (92%)
      had multiple predictors compared to 14 of 33 (42%) who remained infection-free (p
      = 0.005). Ten of these 12 patients (92%) were found to have evidence of
      vesicoureteral reflux when evaluated with voiding cystourethrogram/radionuclide
      cystogram after infection. CONCLUSIONS: This study demonstrates that up to 27% of
      patients treated endoscopically may have a febrile urinary tract infection after
      an initial negative postoperative voiding cystourethrogram/radionuclide cystogram
      at 2 to 5 months and up to 92% of those will demonstrate delayed vesicoureteral
      reflux recurrence. Children with a history of 2 or more predictive factors,
      including multiple febrile urinary tract infections, dysfunctional elimination
      and/or renal cortical defects on dimercapto-succinic acid scan, may not be
      optimal candidates for Deflux. If endoscopic treatment is chosen, these patients
      require more vigilant followup, including late voiding cystourethrogram.

PMID- 18710763
TI  - WAVE1 is associated with invasiveness and growth of prostate cancer cells.
AB  - PURPOSE: WAVE1 belongs to the Wiskott-Aldrich syndrome family of proteins, which
      have an integral part in cell motility, a crucial step in cancer metastasis. We
      investigated the expression pattern and the effects of manipulating endogenous
      WAVE1 expression in prostate cancer cells. MATERIALS AND METHODS: WAVE1 protein
      expression in normal and cancer specimens, and in prostate cell lines was
      assessed using immunohistochemistry and reverse transcriptase-polymerase chain
      reaction, respectively. Hammerhead ribozyme transgenes were synthesized and
      cloned into the mammalian expression vector pEF6/V5-His TOPO TA, and transfected
      by electroporation into PC-3(DeltaW1R1/2) and DU-145(DeltaW1R1/2) cell lines. In
      vitro invasion, adhesion and growth assays were used to assess the impact of
      WAVE1 knockdown. RESULTS: Immunohistochemistry of prostate tissue specimens
      showed that the cytoplasm of cancer cells had stronger staining than normal
      epithelium. Reverse transcriptase-polymerase chain reaction for WAVE1 showed
      strong expression in the PC-3 (European Collection of Cell Cultures, Salisbury,
      United Kingdom) and DU-145 (ATCC(R)) cell lines. WAVE1 knockdown was associated
      with a significant decrease in invasion but not in adhesion. The mean +/- SEM
      number of invading PC-3(DeltaW1R1) and PC-3(DeltaW1R2) cells was 7.27 +/- 0.38
      and 6 +/- 0.29, respectively, compared to 12.27 +/- 0.42 PC-3(WT) cells (p
      <0.001). Similarly the mean number of invading DU-145(DeltaW1R1) and DU
      145(DeltaW1R2) cells was 9.20 +/- 0.70 and 11.60 +/- 0.84 compared to 14.80 +/-
      0.24 DU-145(WT) cells (p <0.001). CONCLUSIONS: To our knowledge this is the first
      report of the expression pattern of WAVE1 in prostate cancer cell lines and
      tissues, and the functional impact of WAVE1 knockdown. Further investigations to
      assess WAVE1 as a potential target for anti-metastasis therapy must be explored.

PMID- 18710764
TI  - The importance of obtaining conjugate views on renographic evaluation of large
      hydronephrotic kidneys: an in vitro and ex vivo analysis.
AB  - PURPOSE: It is postulated that significant obstruction leads to decreased
      ipsilateral renal function. However, maintained or even increased differential
      renal function is often seen in patients with large hydronephrotic kidneys. The
      reason for such a phenomenon is unclear. We designed an in vitro and ex vivo
      experimental model that permits the controlled orientation of thinned renal
      parenchyma and background activity during gamma camera detection. MATERIALS AND
      METHODS: A 5-step experimental study was designed with balloons or reservoirs
      containing known amounts of radioisotope. A balloon was incrementally compressed
      between 2 Plexiglas sheets (step 1). Simultaneous measurement of radio emission
      was done of 5 glass beakers of varying diameters filled with the same amount of
      water and (99m)Tc (step 2). A single beaker containing diluted (99m)Tc was
      interfaced with air (step 3) or water (step 4) at different distances from the
      gamma camera. Pig kidneys previously injected with dimercapto-succinic acid were
      removed and scanned (step 5). One of the kidneys was then progressively sliced,
      thinning its parenchyma, and sliced and nonsliced kidneys were simultaneously
      scanned again. RESULTS: Progressively increased counts were detected as the
      projected surface area of the radioactive balloons (step 1) and beakers (step 2)
      increased. Counts detected were inversely proportional to the amount of water
      interfaced between the container and the gamma camera. Significantly more
      radiation was detectable in sliced kidneys containing dimercapto-succinic acid
      than in intact control kidneys. CONCLUSIONS: These findings suggest that the
      artifactual supranormal differential renal function that is observed during
      renographic evaluation of large hydronephrotic kidneys actually exists.
      Parenchymal proximity and distribution in relation to the pelvis are critical
      determinants. These findings suggest that the conjugate view technique may be
      more suitable for renographic evaluation of large hydronephrotic kidneys.

PMID- 18710765
TI  - One-year followup of renal artery stent graft for blunt trauma.

PMID- 18710766
TI  - New methods of assessing crystal growth and saturation of brushite in whole
      urine: effect of pH, calcium and citrate.
AB  - PURPOSE: Brushite crystallization might be important in stone formation and
      prevention. To explore this question new methods for the saturation and crystal
      growth of brushite were devised that are applicable to whole urine without any
      computer program. MATERIALS AND METHODS: The saturation value (concentration-to
      product ratio) was determined by dividing the molar concentration product of Ca
      ([Ca]) and phosphate ([P]), that is [Ca] x [P], of original urine by the steady
      state solubility obtained after incubating with an excess of brushite (10 mg/ml)
      for 5 hours. Crystal growth was measured from the depletion of filtrate ([Ca] x
      [P]) 3 hours after seeding with brushite (0.25 mg/ml). To test the effect of pH,
      Ca and citrate the saturation value and crystal growth were determined in 24-hour
      urine samples from 4 normal volunteers and 2 stone formers, and modified
      artificially to produce 4 ranges of pH, Ca and citrate by adding acid, base, Ca
      or citrate. RESULTS: The saturation value and crystal growth of brushite
      increased with an increase in pH or the Ca concentration but they decreased when
      the citrate concentration increased. The saturation value correlated strongly
      with crystal growth. CONCLUSIONS: The new methods of brushite saturation value
      and crystal growth should help discern how abnormalities in urinary pH, Ca and
      citrate interact to influence the formation of Ca stones in cases of distal renal
      tubular acidosis and alkali therapy.

PMID- 18710769
TI  - Re: Excise, ablate or observe: the small renal mass dilemma--a meta-analysis and
      review D. A. Kunkle, B. L. Egleston and R. G. Uzzo J Urol 2008; 179: 1227-1234.

PMID- 18710770
TI  - Aggressive angiomyxoma of the male genital region.

PMID- 18710771
TI  - A biphasic response from bladder epithelial cells induced by catheter material
      and bacteria: an in vitro study of the pathophysiology of catheter related
      urinary tract infection.
AB  - PURPOSE: Catheter associated urinary tract infection is the most common type of
      hospital acquired infection. An understanding of catheter associated urinary
      tract infection pathogenesis is needed to improve the control and treatment of
      these infections. We investigated the relationship among catheter material,
      bacteria and bladder epithelial cell reaction. MATERIALS AND METHODS: Urinary
      catheter sections and a clinical isolate of Escherichia coli were added to human
      bladder carcinoma epithelial cells in vitro in combination or independently. The
      catheters were rotated for 30 seconds over the cells, followed by incubation. The
      cytokines interleukin-6 and 8 were measured by enzyme-linked immunosorbent assay
      as indicators of inflammation and cell membrane disruption was assessed using a
      lactate dehydrogenase assay. RESULTS: The levels of lactate dehydrogenase release
      and cytokine production depended on the number of bacteria added. Bacteria grown
      for 3 days caused greater secretion of cytokines than bacteria grown overnight.
      Silicone catheter material alone caused immediate damage to cells with increased
      lactate dehydrogenase in the supernatant but little interleukin-6 or 8
      production. Silicone catheters caused significantly less cytokine secretion from
      bladder cells than latex catheters. Conversely bacteria caused little immediate
      damage to cells but stimulated cytokine production after 12 hours. CONCLUSIONS:
      Disruption of bladder epithelial cell membranes in vitro occurred immediately as
      a result of physical abrasion caused by catheters but delayed inflammation
      occurred in response to bacterial infection.

PMID- 18710774
TI  - Patient controlled versus automatic stimulation of pudendal nerve afferents to
      treat neurogenic detrusor overactivity.
AB  - PURPOSE: We investigated whether patients with neurogenic detrusor overactivity
      can sense the onset of bladder contraction and in turn suppress the contraction
      by electrical stimulation of the dorsal penile-clitoral nerve. MATERIALS AND
      METHODS: A total of 67 patients with different neurological disorders were
      recruited to undergo 3 filling cystometries. The first cystometry was done
      without stimulation. The second cystometry was performed with automatic
      controlled stimulation based on detrusor pressure. The third cystometry was done
      with patient controlled stimulation using a push button. RESULTS: Four females
      and 13 males underwent all 3 fillings. Compared to cystometry 1 average bladder
      capacity for cystometries 2 and 3 was 60% higher. Compared to peak pressure for
      cystometry 1 average peak pressure during suppressed contractions for
      cystometries 2 and 3 was 49% and 26% lower, respectively. The average delay of
      the onset of stimulation during cystometry 3 with respect to cystometry 2 was 5.7
      seconds. CONCLUSIONS: The study shows that patient controlled genital nerve
      stimulation is as effective as automatic controlled stimulation to treat
      neurogenic detrusor overactivity. Thus, patient controlled stimulation is
      feasible in select patients, although patients must be trained in the technique.

PMID- 18710775
TI  - Urine is necessary to provoke bladder inflammation in protamine sulfate induced
      urothelial injury.
AB  - PURPOSE: The bladder is normally impermeable to possible hostile environmental
      factors and toxic urinary wastes. Any disruption of the permeability barrier
      would permit the leakage of urine constituents into the underlying cells layers
      and subsequent inflammation. Protamine sulfate, which increases urothelial
      permeability, is used in experimental models of cystitis. We examined whether
      protamine sulfate alone could cause bladder inflammation or if the association of
      protamine sulfate and urine is needed for this condition. MATERIALS AND METHODS:
      Female Wistar rats (Center for the Development of Experimental Models for
      Medicine and Biology, Federal University of Sao Paulo, Sao Paulo, Brazil) had the
      bladder catheterized and instilled with protamine sulfate (10 mg) or sterile
      saline for 30 minutes. To exclude urine other groups of rats underwent bilateral
      nephrectomy and the same procedure was used. One day after instillation the
      bladders were removed for histopathology. Edema and vascular congestion were
      graded from 0-none to 3-severe. Polymorphonuclear and mast cells were counted.
      The Kruskal-Wallis test was performed for statistical analysis. RESULTS:
      Intravesical instillation of protamine sulfate in nonnephrectomized rats led to
      inflammation, in contrast to findings in rats instilled with saline. On the other
      hand, nephrectomized rats showed no inflammatory changes following the
      instillation of protamine sulfate or saline. The mast cell count was similar in
      all groups. CONCLUSIONS: Bladder inflammation in this experimental model of
      urothelial injury was not due to protamine sulfate alone. The association of
      protamine sulfate and urine was necessary to trigger the inflammatory cascade.
      Thus, urine indeed has an important role in the development of bladder
      inflammation in an environment of higher urothelial permeability.

PMID- 18710776
TI  - Photoselective vaporization of the prostate using a laser high performance system
      in the canine model.
AB  - PURPOSE: Photoselective vaporization of the prostate with the 80 W KTP laser has
      been shown to be an effective and durable therapy for benign prostatic
      hyperplasia. We investigated the new, more powerful GreenLight HPS(R) High
      Performance System laser in the canine model as a more rapid treatment for benign
      prostatic hyperplasia. MATERIALS AND METHODS: Five male beagles underwent general
      anesthesia and laparotomy. Photoselective vaporization of the prostate was
      performed in antegrade fashion through a suprapubic cystotomy at 40, 80 and 120 W
      at 3 firing periods (5, 10 and 20 seconds). Photoselective vaporization of the
      prostate was performed for each power and time combination in stationary fashion
      at unique locations. Prostates were harvested and histopathological analysis was
      performed. Mean vaporization and coagulation depths of each laser setting were
      determined and compared using ANOVA. RESULTS: Vaporization depth was 4 mm to full
      thickness. Coagulation occurred 1.2 to 2.5 mm deep to the vaporization zone.
      Increasing laser power appeared to increase depth of vaporization with equivalent
      or less coagulation depth and increasing the lasing duration behaved similarly.
      Microscopic pathological evaluation revealed damage to adjacent tissues in areas
      of full-thickness vaporization at the longest exposure times. CONCLUSIONS: The
      HPS laser is capable of greater power than the 80 W KTP system. HPS laser beam
      effects appeared more optically confined than those of its lower power brethren.
      It consistently vaporized more tissue during a given period while maintaining a 1
      to 2 mm rim of coagulation, like its predecessors. The HPS should be applied
      carefully due to the ability to rapidly create full-thickness tissue
      vaporization.

PMID- 18710778
TI  - Nutrient and sediment removal by stormwater biofilters: a large-scale design
      optimisation study.
AB  - A large-scale column study was conducted in Melbourne, Australia, to test the
      performance of stormwater biofilters for the removal of sediment, nitrogen and
      phosphorus. The aim of the study was to provide guidance on the optimal design
      for reliable treatment performance. A variety of factors were tested, using 125
      large columns: plant species, filter media, filter depth, filter area and
      pollutant inflow concentration. The results demonstrate that vegetation selection
      is critical to performance for nitrogen removal (e.g. Carex appressa and
      Melaleuca ericifolia performed significantly better than other tested species).
      Whilst phosphorus removal was consistently very high (typically around 85%),
      biofilter soil media with added organic matter reduced the phosphorus treatment
      effectiveness. Biofilters built according to observed 'optimal specifications'
      can reliably remove both nutrients (up to 70% for nitrogen and 85% for
      phosphorus) and suspended solids (consistently over 95%). The optimally designed
      biofilter is at least 2% of its catchment area and possesses a sandy loam filter
      media, planted with C. appressa or M. ericifolia. Further trials will be required
      to test a wider range of vegetation, and to examine performance over the longer
      term. Future work will also examine biofilter effectiveness for treatment of
      heavy metals and pathogens.

PMID- 18710777
TI  - A comparison of open vs laparoscopic pediatric pyeloplasty using the pediatric
      health information system database--do benefits of laparoscopic approach recede
      at younger ages?
AB  - PURPOSE: The potential benefits of laparoscopic pyeloplasty may recede in younger
      age groups. We used a multi-institutional database to address the effect of
      laparoscopic approach on length of stay and postoperative parenteral narcotic use
      in specific pediatric age groups. MATERIALS AND METHODS: We performed a
      retrospective study of 5,261 children with an ICD-9 procedure code for correction
      of ureteropelvic junction obstruction from the Pediatric Health Information
      System, a database of freestanding pediatric hospitals. Discharge dates from
      January 1, 2002 to June 30, 2007 were included. Laparoscopic cases were
      identified by ICD-9 procedure codes and hospital equipment charges. We used
      multivariate linear regression to investigate the effect of laparoscopic approach
      on length of stay and parenteral narcotic use in several age categories,
      including infant (1 month to less than 2 years old), preschool (2 to less than 6
      years), grade school (6 to less than 10 years), preadolescent (10 to less than 13
      years) and adolescent (13 to less than 19 years). RESULTS: Laparoscopic approach
      decreased length of stay and number of parenteral narcotic pharmacy charges in
      the preadolescent (p = 0.03 and p = 0.005, respectively) and adolescent (p = 0.03
      and p = 0.006, respectively) groups but not in any of the younger groups.
      CONCLUSIONS: Laparoscopic approach was associated with a shorter hospital stay
      and decreased parenteral narcotic use in patients older than 10 years. Evolving
      technique may reveal less morbidity in younger patients. Future comparisons to
      open pyeloplasty should address specific pediatric age groups and outpatient
      convalescence.

PMID- 18710779
TI  - Polar organic marker compounds in PM2.5 aerosol from a mixed forest site in
      western Germany.
AB  - The molecular composition of PM2.5 (particulate matter with an aerodynamic
      diameter <2.5 microm) aerosol samples collected during a very warm and dry 2003
      summer period at a mixed forest site in Julich, Germany, was determined by gas
      chromatography/mass spectrometry in an effort to evaluate photooxidation products
      of biogenic volatile organic compounds (BVOCs) and other markers for aerosol
      source characterization. Six major classes of compounds represented by twenty
      four individual organic species were identified and measured, comprising tracers
      for biomass combustion, short-chain acids, fatty acids, sugars/sugar alcohols,
      and tracers for the photooxidation of isoprene and alpha-/beta-pinene. The
      tracers for the photooxidation of alpha-/beta-pinene include two compounds, 3
      hydroxyglutaric acid and 3-methyl-1,2,3-butanetricarboxylic acid, which have only
      recently been elucidated. The characteristic molecular distribution of the fatty
      acids with a strong even/odd number carbon preference indicates a biological
      origin, while the presence of isoprene and terpene secondary organic aerosol
      products suggests that the photooxidation of BVOCs contributes to aerosol
      formation at this site. The sum of the median concentrations of the isoprene
      oxidation products was 21.2 ng m(-3), while that of the terpene oxidation
      products was 19.8 ng m(-3). On the other hand, the high median concentration of
      malic acid (37 ng m(-3)) implies that photooxidation of unsaturated fatty acids
      should also be considered as an important aerosol source process. In addition,
      the occurrence of levoglucosan and pyrogallol indicates that the site is affected
      by biomass combustion. Their median concentrations were 30 and 8.9 ng m(-3),
      respectively.

PMID- 18710780
TI  - Current status of thrombolytics-the need for better, especially safer, agents.
AB  - Clot dissolution using enzymes from the human fibrinolytic system has long been a
      goal of physicians and scientists. While recent focus has been on activators of
      the fibrinolytic system, new data support the use of plasmin itself. This
      supplement reviews the role of plasmin in fibrinolysis and locally administered
      plasmin as a safe and effective therapeutic.

PMID- 18710781
TI  - The use of bevacizumab in refractory ovarian granulosa-cell carcinoma with
      symptomatic relief of ascites: a case report.
AB  - BACKGROUND: The potential role of bevacizumab in the treatment of ovarian
      granulosa-cell tumors has not been evaluated. CASE: An 82 year old woman with
      refractory ovarian granulosa-cell carcinoma was treated with bevacizumab with
      symptomatic relief of ascites. CONCLUSION: Bevacizumab may have a role in the
      management of malignant ascites in the patient with refractory granulosa-cell
      carcinoma of the ovary which should be confirmed in a larger series of well
      selected patients.

PMID- 18710782
TI  - Multidimensional social control variables as predictors of drunkenness among
      French adolescents.
AB  - BACKGROUND: Previous studies of the determinants of drunkenness among youth
      investigated the contribution of a limited range of variables measuring social
      control. For the first time in France, this study including 1295 participants
      aged 14-19 years aimed at assessing the relative contribution of a broad range of
      multidimensional variables relating to social control such as parental and school
      functioning, conventional and religious beliefs, and activity level, in a single
      model predicting self-reported drunkenness episodes. METHODS: A logistic
      regression model based on a survey involving nearly 50 measures selected at the
      first step was conducted using a backward elimination procedure to identify the
      significant predictors of drunken experience controlling for age, gender and SES
      among a sample of French adolescents. RESULTS: We found a protective effect of
      attachment and commitment to institutions in drunkenness experience among youth.
      Previous findings on parental variables were confirmed with qualifications,
      whereas the effect of religion was limited. The negative role of sport practice
      and impulsivity was also emphasized for some participants.

PMID- 18710783
TI  - Predictive validity of the Family Attitude Scale in people with psychosis.
AB  - Expressed Emotion (EE) strongly predicts relapse in mental disorders, but there
      remains a need to develop and refine brief, self-report measures. This article
      describes two studies testing the validity of a self-report measure of criticism
      or burden, the Family Attitude Scale (FAS), in relatives of patients with
      psychosis. Study 1 had 54 families of patients with psychosis and a substance use
      disorder, while Study 2 had 61 families of patients at an early psychotic
      episode. In Study 1, a consensus FAS was obtained; in Study 2 separate parental
      scores were used. The FAS was positively associated with EE, and with
      relationship negativity. Associations with negative caregiving experiences or
      stress were restricted to maternal or consensual FAS ratings. FAS scores
      predicted relapse in both studies, although prediction at the optimal cutoff
      (>or=60) only reached statistical significance in Study 2, and time to relapse
      was only predicted by the FAS in Study 1. Prediction of relapse from the CFI was
      stronger, and the FAS did not add to that prediction. Results supported the
      utility of the FAS, but confirmed the pre-eminence of the CFI as a household
      related predictor of relapse.

PMID- 18710784
TI  - Association of cognitive distortions with problem and pathological gambling in
      adult male twins.
AB  - Treatment studies suggest that gambling-related irrational beliefs and attitudes
      (i.e., cognitive distortions (CDs)) contribute to the risk for problem gambling
      behavior. In a community sample of men, we investigated the associations among
      lifetime gambling-related CDs, psychiatric disorders other than pathological
      gambling , and problem gambling severity. Subjects were 1354 members of the
      Vietnam Era Twin Registry. Problem gambling and gambling-related CDs were derived
      from a 2002 interview using the National Opinion Research Center DSM-IV Screen
      for Gambling Problems (NODS). Exploratory factor analysis was performed with the
      12 CD items to identify an underlying construct. Generalized linear models were
      computed to test for associations among CDs, psychiatric disorders other than
      pathological gambling, and gambling problem severity. Co-twin control analyses of
      monozygotic twin pairs discordant for problem gambling severity adjusted for
      genetic and shared environmental influences. Twelve CD items related to one
      underlying CD construct. After adjustment for lifetime psychiatric disorders,
      pathological gambling symptoms were positively associated with higher CD scores.
      Pathological gambling symptoms remained significantly associated with CD scores
      after controlling for genetic and shared environmental influence. These results
      provide empirical support for an association between gambling-related CDs and
      gambling problem severity, even after controlling for genetic and shared
      environmental influences and non-pathological gambling psychiatric disorders.
      Public health messages and therapeutic interventions that reinforce the
      randomness of gambling and draw attention to distorted thinking may prevent the
      development of problem gambling and improve treatment outcomes.

PMID- 18710785
TI  - Association between physical illnesses and depressive symptoms requiring
      hospitalization in suicide victims.
AB  - We examined an association between a history of hospital-treated depression and
      physical diseases in 1877 suicide victims from Northern Finland. Information on
      physical diseases and depression of victims was extracted from the Finnish
      Hospital Discharge Registers. Of suicide victims, 31% of female and 16% of male
      victims had a lifetime history of depression. When compared with victims without
      any lifetime hospital-treated physical illnesses, a history of depression was
      shown to associate with the diseases of the nervous, circulatory, respiratory,
      and musculoskeletal systems in the group of symptoms and signs, injuries and
      poisonings, and infectious diseases among male victims. Respectively, in female
      victims, an increased prevalence of depression was seen in endocrine, nutritional
      and metabolic diseases, diseases of the nervous, circulatory, genitourinary, skin
      and subcutaneous tissue, and musculoskeletal systems, and with injuries and
      poisonings, pregnancy-related problems and infectious diseases. This study is the
      first to evaluate comorbidity between physical illnesses and depression over the
      lifetime in suicide victims; earlier studies reported findings in living patients
      from epidemiological or clinical populations. Since depression can affect quality
      of life in severely ill patients, targeting depression in patients with chronic
      illness may assist in decreasing suicide rates.

PMID- 18710786
TI  - Birth measures and depression at age 31 years: the Northern Finland 1966 Birth
      Cohort Study.
AB  - The aim of the study was to explore whether there is an association between body
      size at birth measured by birth weight and ponderal index and later depression at
      the age of 31 years. The analyses were based on 4,007 males and 4,332 females
      born in 1966 in the two northernmost provinces of Finland with data on current
      depression measured by the Hopkins Symptom Checklist-25 questionnaire (HSCL-25)
      and self-reported physician-diagnosed lifetime depression at 31 years and
      childhood characteristics. The associations between birth measures and later
      depression were analysed with several confounding factors including maternal
      depression during pregnancy. Low birth measures did not associate with adult
      depression in men or women. Women with high birth weight (>or=4,500 g) had a
      higher risk for current depression compared to women with birth weight 3,000 g
      3,499 g. Women with high ponderal index (the highest 90-95 percentiles and >or=95
      percentiles) had a 1.53-1.55 higher likelihood for current depression compared
      with women with normal ponderal index. Based on this study, large body size at
      birth may be a risk factor for later depression.

PMID- 18710787
TI  - JAK2-STAT3 signaling pathway mediates thrombin-induced proinflammatory actions of
      microglia in vitro.
AB  - The present study shows that JAK2-STAT3 inflammatory signaling mediates thrombin
      stimulated microglia activation. In rat primary microglia, thrombin rapidly
      activated JAK2 and induced phosphorylation of STAT3. In addition, thrombin
      increased transcription of the inflammation-associated genes tumor necrosis
      factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), production of TNF
      alpha, NO and induced neurodegeneration of dopaminergic neurons in mesencephalic
      cultures. AG490, a JAK inhibitor, markedly reduced activation of JAK2 and STAT3
      in thrombin-treated microglia. AG490 also inhibited thrombin-induced
      transcription and expression of TNF-alpha, iNOS and/or NO release, moreover
      rescued dopaminergic neurons. These results suggest that JAK2-STAT3 signaling
      pathway plays a critical role in mediating thrombin-induced activation of
      microglia and degeneration of dopaminergic neurons.

PMID- 18710788
TI  - Use of flow cytometry in an apoptosis assay to determine pH and temperature
      stability of shiga-like toxin 1.
AB  - Shiga toxins and Shiga-like toxins (Stx) are a relatively large group of
      cytotoxins produced by certain serotypes of Shigella and E. coli (STEC). These
      toxins are responsible for diarrhea, hemorrhagic colitis and may induce hemolytic
      uremic syndrome (HUS) with serious consequences in young children. The toxins are
      proteins made up of 5 small B subunits responsible for binding to an outer
      membrane ligand on host cells and surround the larger, biologically active A
      subunit. For Shiga-like toxin 1 (Stx1), the cellular receptor is the carbohydrate
      globotriose. Stx1was purified from STEC. We utilized induction of apoptosis in
      the human monocyte cell line THP-1, as a biological endpoint to test the
      stability of Stx1 activity added to fruit punch at different pH (2-9) and
      temperatures (4 and 20 degrees C). A flow cytometric method was used to test for
      early and late apoptotic events based on binding of R-phycoerytherin-labeled
      annexin V to exposed membrane phosphatidyl serine. Membrane permeability to 7
      Amino-actinomycin corresponds with late apoptosis or necrosis. The combination of
      acid pH and higher storage temperature resulted in greatest degree of toxin
      inactivation. This approach provides a rapid and high throughput method to
      determine the functional activity of Stx1, and related toxins in a food matrix.

PMID- 18710789
TI  - Selection and use of autochthonous mixed starter for lactic acid fermentation of
      carrots, French beans or marrows.
AB  - Strains of Leuconostoc mesenteroides, Lactobacillus plantarum, Weissella
      soli/Weissella koreensis, Enterococcus faecalis, Pediococcus pentosaceus and
      Lactobacillus fermentum were identified from raw carrots, French beans and
      marrows by partial 16S rRNA gene sequence. L. plantarum M1, Leuc. mesenteroides
      C1 and P. pentosaceus F4 were selected based on the rates of growth and
      acidification in vegetable juice media, and used as the autochthonous mixed
      starter for the fermentation of carrots, French beans or marrows. An
      allochthonous starter, consisting of the same species, was also used for
      fermentation. A two-step fermentation process (1 day at 25 degrees C and 7 days
      at 15 degrees C) in brine (1% w/v) followed by storage at room temperature in
      olive oil until 40 days was set up. Unstarted vegetables subjected to the same
      treatments were used as the controls. Cell numbers of lactic acid bacteria in the
      started vegetables were ca. 10,000 (autochthonous starter) and 1000
      (allochthonous starter) times higher than unstarted samples throughout the
      process. When fermented with the autochthonous starter, carrots, French beans or
      marrows were characterized by the rapid decrease of pH (<4.5), marked consumption
      of fermentable carbohydrates, and inhibition of Enterobacteriaceae and yeasts.
      Fermentation with the allochthonous starter did not acidify and inhibit bacteria
      and yeasts so rapidly. After 40 days, carrots, French beans and marrows fermented
      with the autochthonous starter had significantly (P<0.05) higher total
      concentration of vitamin C (ascorbate+dehydroascorbate) with respect to those
      fermented with the allochthonous starter and, especially unstarted vegetables.
      The same was found for the indexes of color. Firmness of both started vegetables
      was higher than unstarted vegetables. Sensory analysis differentiated started
      vegetables. Carrots and French beans fermented with the autochthonous starter
      were, especially, appreciated for fragrance. Appearance was the sensory attribute
      that mainly distinguished marrows fermented with the autochthonous starter.

PMID- 18710790
TI  - Myosin light-chain kinase contributes to the proliferation and migration of
      breast cancer cells through cross-talk with activated ERK1/2.
AB  - Myosin light-chain kinase (MLCK) plays a crucial role in the cell migration and
      tumor metastasis. Herein, we investigated the signaling pathways involved in MLCK
      using ML-7, a specific inhibitor of MLCK, in breast cancer cell proliferation and
      migration. Our data showed that reduction of MLCK in breast cancer cells mediated
      by 20 microM ML-7 was able to depress the cell proliferation and migration using
      two parallel cell lines (MCF-7 and LM-MCF/MDA-MB-231) with different metastatic
      abilities through reciprocal cross-talk with activated ERK1/2, in which both
      phosphorylated myosin light chain (p-MLC) and cascades of beta-catenin, cyclin
      D1, survivin, and c-Myc serve as essential downstream effectors.

PMID- 18710791
TI  - Multiple sclerosis: could it be an epigenetic disease?
AB  - Multiple sclerosis (MS) is the most frequent autoimmune, inflammatory disease of
      the central nervous system. It is believed to be a multifactorial and multigenic
      disease. Despite numerous efforts to find a locus with hypothesis-free whole
      genome screens, no repeatable locus other than HLA could be found. Genomic
      screens use polymerase chain reaction (PCR) based methods to find a difference
      between patients and controls. This method is insensitive to differences other
      than disparities in the DNA sequence. The negative results of these efforts
      suggest that other mechanisms may be involved in MS pathophysiology. Epigenetics
      denotes all heritable mechanisms which result in a transcriptional difference
      without a change in the DNA sequence. In the last decade, there have been several
      findings implying the significance of epigenetic modifications as causal factors
      for multifactorial diseases like MS. Epigenetic factors might be affecting MS
      induction and clinical severity by modulating such diverse biological processes
      as X chromosome inactivation, viral infections, myelin protein production and Th1
      type immune response differentiation.

PMID- 18710792
TI  - Is ZMP the toxic metabolite in Lesch-Nyhan disease?
AB  - The genetic deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT),
      located on the X chromosome, causes a severe neurological disorder in man, known
      as Lesch-Nyhan disease (LND). The enzyme HPRT is part of the savage pathway of
      purine biosynthesis and catalyzes the conversion of hypoxanthine and guanine to
      their respective nucleotides, IMP and GMP. HPRT deficiency is associated with a
      relatively selective dysfunction of brain dopamine systems. Several metabolites
      that accumulate in the patients (phosphoribosylpyrophosphate (PRPP),
      hypoxanthine, guanine, xanthine, and Z-nucleotides) have been proposed as toxic
      agents in LND. Some authors have pointed that Z-riboside, derived from the
      accumulation of ZMP, could be the toxic metabolite in LND. However, the available
      experimental data support a better hypothesis. I suggest that ZMP (and not Z
      riboside) is the key toxic metabolite in LND. ZMP is an inhibitor of the
      bifunctional enzyme adenylosuccinate lyase, and a deficiency of this enzyme
      causes psychomotor and mental retardation in humans. Moreover, it has been
      reported that ZMP inhibits mitochondrial oxidative phosphorylation and induces
      apoptosis in certain cell types. ZMP is also an activator of the AMP-activated
      protein kinase (AMPK), a homeostatic regulator of energy levels in the cell. The
      AMPK has been implicated in the regulation of cell viability, catecholamine
      biosynthesis and cell structure. I propose that accumulation of ZMP will induce a
      pleiotropic effect in the brain by (1) a direct inhibition of mitochondrial
      respiration and the bifunctional enzyme adenylosuccinate lyase, and (2) a
      sustained activation of the AMPK which in turns would reduce cell viability,
      decrease dopamine synthesis, and alters cell morphology. In addition, a mechanism
      to explain the accumulation of ZMP in LND is presented. The knowledge of the
      toxic metabolite, and the way it acts, would help to design a better therapy.

PMID- 18710793
TI  - Blockade of the advanced glycation end products (AGEs) and their receptor (RAGE)
      system is a possible mechanism for sustained beneficial effects of multifactorial
      intervention on mortality in type 2 diabetes.
AB  - Steno-2 Study has previously shown that intensified multifactorial intervention
      reduces the risk of nonfatal cardiovascular disease in patients with type 2
      diabetes. Further, in the recent follow-up study, intensive therapy was found to
      have sustained beneficial effects on cardiovascular events and death in this
      population. A similar outcome was reported in the Diabetes Control and
      Complications Trial/Epidemiology of Diabetes Interventions and Complications
      (DCCT-EDIC) Research, which revealed that original intensive therapy reduced the
      risk of cardiovascular events to about 50% of that of conventional treatment in
      type 1 diabetic patients 11 years after the end of the trial, although
      glycosylated hemoglobin values in the two groups had almost converged during the
      follow-up periods. These two clinical studies strongly suggest that so-called
      'metabolic memory' causes chronic vascular damage in diabetic patients, that are
      not easily reversed, even by subsequent, relatively good control of metabolic
      risk factors. Potential mechanisms for propagating this 'metabolic memory' are
      the non-enzymatic glycation of proteins. Indeed, the formation and accumulation
      of advanced glycation end products (AGEs) have been known to progress at an
      accelerated rate under diabetes, and there is accumulating evidence that AGEs
      their receptor RAGE interaction elicits oxidative stress generation and
      subsequently evokes vascular inflammation, thus being involved in the
      pathogenesis of accelerated atherosclerosis in diabetes. Since renin-angiotensin
      system inhibitors or a lipid-lowering agent, atorvastatin, not only inhibit the
      AGE-signaling to inflammation, but also reduce serum levels of AGEs in type 2
      diabetic patients, it is conceivable that the carry-over beneficial effects of
      multifactorial intervention on cardiovascular events and death in the follow-up
      Steno-2 Study could be ascribed, at least in part, to its inhibitory effects on
      AGE formation and/or the downstream-signaling pathways. Therefore, it is
      interesting to clarify whether circulating or skin AGE levels at the closure of
      Steno-2 Study could predict cardiovascular events at the end of the trial. This
      clinical investigation may provide us more information about whether blockade of
      the AGE-RAGE system is one of the mechanisms for sustained beneficial effects of
      multifactorial intervention on mortality in type 2 diabetes.

PMID- 18710794
TI  - Mule or hinny might be a natural model for studying the role of parent genomes in
      carcinogenesis.

PMID- 18710795
TI  - Combining experts in order to identify binding sites in yeast and mouse genomic
      data.
AB  - The identification of cis-regulatory binding sites in DNA is a difficult problem
      in computational biology. To obtain a full understanding of the complex machinery
      embodied in genetic regulatory networks it is necessary to know both the identity
      of the regulatory transcription factors and the location of their binding sites
      in the genome. We show that using an SVM together with data sampling to classify
      the combination of the results of individual algorithms specialised for the
      prediction of binding site locations, can produce significant improvements upon
      the original algorithms. The resulting classifier produces fewer false positive
      predictions and so reduces the expensive experimental procedure of verifying the
      predictions.

PMID- 18710796
TI  - NKT lymphocyte polarization determined by microenvironment signaling: a role for
      CD8+ lymphocytes and beta-glycosphingolipids.
AB  - Natural killer T-cell (NKT) regulatory lymphocytes have been shown to behave
      differently in various immune settings. The aim of the present study was to
      determine the effect of microenvironmental signaling on NKT polarization and the
      process of active CD8 and NKT intrahepatic lymphocyte sequestration. In an in
      vitro assay, double negative (DN) NKT hybridoma cells were incubated with Hep3B
      hepatoma cells. This caused a significant increase in the secretion of alpha
      fetoprotein (AFP) from Hep3B cells. When NKT cells were exposed to beta
      glucoslyceramide (beta-GC) prior to incubation, Hep3B cells exhibited increased
      proliferation, increased IFN secretion, and reduced AFP secretion. In vivo, the
      adoptive transfer of naive DN NKT cells into athymic nude-nu mice transplanted
      with human Hep3B hepatocellular carcinoma (HCC) caused accelerated tumor growth.
      This effect was inhibited by prior ex vivo exposure of DN NKT lymphocytes to beta
      GC. To assess the effect of the immunological environment on NKT cells, immune
      mediated hepatitis and colitis were induced simultaneously in mice. Induction of
      TNBS colitis prior to administration of concanavalin A (Con A) hepatitis resulted
      in an aggravation of the liver damage caused by Con A hepatitis alone. This
      effect was associated with reduced intrahepatic CD8+ T cell trapping and an
      increase in intrahepatic NKT cells. The presence of different ligands altered
      host microenvironment signaling and influenced the fate and polarization of NKT
      cells and the sequestration of active intrahepatic lymphocytes. These data
      support the notion that NKT regulatory lymphocytes have an inherent plasticity
      that may be important for their regulatory function.

PMID- 18710797
TI  - Glutamic acid decarboxylase (GAD) antibodies in tardive dyskinesia (TD) as
      compared to patients with schizophrenia without TD and normal controls.

PMID- 18710798
TI  - Amisulpride the 'atypical' atypical antipsychotic--comparison to haloperidol,
      risperidone and clozapine.
AB  - INTRODUCTION: Amisulpride's high and selective affinity for dopamine D2/3 (Ki
      1.3/2.4 nM) receptors, lack of affinity for serotonin receptors, and its
      unusually high therapeutic doses (400-800 mg/day) makes it unique among atypical
      antipsychotics and prompted us to compare its actions with other antipsychotics
      in animal models. METHODS: Amisulpride's effects on amphetamine and phencyclidine
      induced locomotor activity (AIL/PIL), conditioned avoidance response, catalepsy
      (CAT), subcortical Fos expression, and plasma prolactin was correlated to its
      time-course striatal D2/3 and prefrontal 5-HT2 receptor occupancy (D(2/3)/5
      HT2RO); in comparison to haloperidol, clozapine, and risperidone. RESULTS: Unlike
      the atypicals clozapine and risperidone, amisulpride lacked 5-HT2RO and showed a
      'delayed' pattern of D2/3RO: 43, 60 and 88% after 1, 2 and 6 h (100 mg/kg),
      respectively, despite a quick onset (1 h) and decline (6 h) of prolactin
      elevation. While haloperidol and risperidone were effective at D2RO>60%,
      clozapine at D2/3RO<50%, amisulpride was effective only when its D2RO exceeded
      60% with a delayed latency and lasted longer than other antipsychotics. CAT was
      observed for haloperidol and risperidone when D2RO exceeded 80%, while in the
      case of amisulpride, CAT was not observed even when doses exceeded 90% D2/3RO.
      Amisulpride also displayed functional limbic selectivity in Fos expression like
      the other atypicals. CONCLUSIONS: Amisulpride's "delayed" functional profile on
      acute administration and the need for high doses is most likely due to its poor
      blood-brain-barrier penetration; however, it is distinct from other atypicals in
      showing low motor side-effects, activity against phencyclidine, and a mesolimbic
      preference, despite no action on serotonin receptors.

PMID- 18710799
TI  - Variation of diameter distribution, number density, and area fraction of fibrils
      within five areas of the rabbit patellar tendon.
AB  - The purpose of this investigation is to show microstructural information at
      various regions within the rabbit patellar tendon. The properties of the rabbit
      patellar tendon are well documented mechanically, but detailed information at the
      microscopic level is not available. Increasing attention has been directed to
      soft tissue microscopy as the demand for development of biologically inspired
      materials increases. Microstructural examination of the tendon fibrils is
      performed to provide further insight into understanding of the structure to
      function relations within the rabbit patellar tendon. Limited studies on rabbit
      patellar tendon collagen fibrils at the microscopic level have been computed.
      Furthermore, evaluation of structure-function relations in multiple regions of
      any given specimen of a particular tissue type has not been conducted. In this
      study the number density, area fraction, and diameter distribution of collagen
      fibrils have been determined. Overall, this examination showed considerable
      variation within each section of the tendon. Correlating these structural results
      with mechanical tests of the tendon portions in the various regions could provide
      additional information on the mechanics of the rabbit tendon as well as insight
      into development of artificial tissue constructs.

PMID- 18710800
TI  - Influence of free air space on microbial kinetics in passively aerated compost.
AB  - The influence of free air space (FAS) on passively aerated composting has been
      reported, but the quantitative relationship between FAS and the microbial
      kinetics in passively aerated compost has not been investigated. This
      relationship was studied by composting dairy manure and straw in an enclosed,
      passively aerated, cylindrical vessel. Based on this experimental system,
      conceptual and numerical models were developed in which the compost bed was
      considered to consist of layered elements, each being physically and chemically
      homogeneous. The microbial activity in each layer was represented in order to
      predict oxygen and substrate consumption and the release of water and heat.
      Convective transport of air, moisture, and heat through the layers was
      represented. Microbial growth and substrate consumption rates were described
      using modified first-order kinetics for each of the mesophilic and thermophilic
      temperature regimes. The values of the microbial kinetic parameters were adjusted
      for each layer based on an innovative, non-linear, statistical analysis of
      temperature histories recorded at different layers in the compost bed during
      three treatments (i.e., FAS values of 0.45, 0.52, and 0.65). Microbial kinetic
      rate constants were found to follow a sigmoid relationship with FAS, with
      correlation coefficients (R(2)) of 0.97 for the mesophilic stage and 0.96 for the
      thermophilic stage. Temperature histories and airflow measurements from a fourth
      treatment (FAS value of 0.57) were used as an independent check of the model's
      performance. Simulation results indicate that the model could predict the general
      trend of temperature development. A plot of the residuals shows that the model is
      biased, however, possibly because many parameters in the model were not measured
      directly but instead were estimated from literature. The result from this study
      demonstrates a new method for describing the relationship between microbial
      kinetics (k(max)) and substrate FAS, which could be used to improve the design,
      optimization, and management of passively aerated composting facilities.

PMID- 18710801
TI  - Environment-friendly adhesives for surface bonding of wood-based flooring using
      natural tannin to reduce formaldehyde and TVOC emission.
AB  - The objective of this research was to develop environment-friendly adhesives for
      face fancy veneer bonding of engineered flooring using the natural tannin form
      bark in the wood. The natural wattle tannin adhesive were used to replace UF
      resin in the formaldehyde-based resin system in order to reduce formaldehyde and
      volatile organic compound (VOC) emissions from the adhesives used between
      plywoods and fancy veneers. PVAc was added to the natural tannin adhesive to
      increase viscosity of tannin adhesive for surface bonding. For tannin/PVAc hybrid
      adhesives, 5%, 10%, 20% and 30% of PVAc to the natural tannin adhesives were
      added. tannin/PVAc hybrid adhesives showed better bonding than the commercial
      natural tannin adhesive with a higher level of wood penetration. The initial
      adhesion strength was sufficient to be maintained within the optimum initial tack
      range. The standard formaldehyde emission test (desiccator method), field and
      laboratory emission cell (FLEC) and VOC analyzer were used to determine the
      formaldehyde and VOC emissions from engineered flooring bonded with commercial
      the natural tannin adhesive and tannin/PVAc hybrid adhesives. By desiccator
      method and FLEC, the formaldehyde emission level of each adhesive showed the
      similar tendency. All adhesives satisfied the E(1) grade (below 1.5 mg/L) and
      E(0) grade (below 0.5 mg/L) with UV coating. VOC emission results by FLEC and VOC
      analyzer were different with the formaldehyde emission results. TVOC emission was
      slightly increased as adding PVAc.

PMID- 18710802
TI  - Using tea stalk lignocellulose as an adsorbent for separating decaffeinated tea
      catechins.
AB  - Lignocelluloses prepared from woody tea stalk, pine sawdust and sugarcane bagasse
      were used as adsorbents to isolate decaffeinated catechins from tea extracts and
      compared with synthetic macroporous resin HPD 600. HPD 600 had the highest
      adsorption capacity to catechins, followed by tea stalk lignocellulose while
      lignocelluloses of pine sawdust and bagasse the least. Tea stalk lignocellulose
      absorbed preferentially tea catechins and showed a good selectivity. HPD 600
      absorbed caffeine and tea catechins simultaneously. The kinetics data of tea
      stalk lignocellulose showed a good fit with the Langmuir isotherm model. It is
      considered that tea stalk lignocellulose is an alternative low-cost adsorbent for
      preparing decaffeinated tea catechins.

PMID- 18710803
TI  - Triphenylmethylamides (TPMAs): Structure-activity relationship of compounds that
      induce apoptosis in melanoma cells.
AB  - Triphenylmethylamides (TPMAs) have been previously identified as compounds that
      arrest cells in the G1-phase of the cell cycle and induce apoptotic death in
      melanoma cell lines in culture. Here we report the synthesis of a series of TPMA
      derivatives, allowing the structure-activity relationship of this class of
      molecules to be established. Several new compounds have been identified that
      induce death in UACC-62 and SK-MEL-5 human melanoma cell lines, including a
      compound with enhanced aqueous solubility.

PMID- 18710804
TI  - Design, synthesis, biochemical, and biological evaluation of nitrogen-containing
      trifluoro structural modifications of combretastatin A-4.
AB  - A new trifluorinated amino-combretastatin analogue, (Z)-2-(4'-methoxy-3'
      aminophenyl)-1-(3,4,5-trifluorophenyl)ethene, prepared by chemical synthesis, was
      found to be a potent inhibitor of tubulin assembly (IC(50)=2.9 microM), and
      cytotoxic against selected human cancer cell lines. This new lead compound is
      among the most active from a group of related structural modifications.

PMID- 18710805
TI  - Synthesis and anti-CVB 3 evaluation of substituted 5-nitro-2
      phenoxybenzonitriles.
AB  - The synthesis and SAR of a series of 60 substituted 2-phenoxy-5
      nitrobenzonitriles (analogues of MDL-860) as inhibitors of enterovirus
      replication (in particular of coxsackievirus B3 (CVB 3)) are reported. Several of
      the analogues inhibited CVB 3 and other enteroviruses at low-micromolar
      concentrations.

PMID- 18710806
TI  - Spontaneous regression of syringomyelia--review of the current aetiological
      theories and implications for surgery.
AB  - A number of hypotheses have been postulated to explain the development of
      syringomyelia associated with Chiari I malformation. However, the mechanism of
      syrinx development is still poorly understood. Furthermore, the outcomes of
      current surgical procedures have been variable. There is evidence that the
      syringomyelia can spontaneously resolve, and this may warrant a more conservative
      approach to monitor the progression of neurological deficits. In this paper, we
      present a patient with spontaneous regression of syringomyelia. The current
      aetiological theories are discussed.

PMID- 18710807
TI  - Primary central nervous system leukemia presenting with an isolated oculomotor
      palsy.
AB  - We present a patient with an isolated oculomotor nerve palsy due to central
      nervous system leukemia with bone marrow findings consistent with myelofibrosis
      without any blasts. This has not been previously reported.

PMID- 18710808
TI  - Lumboperitoneal shunt for treatment of dural ectasia in ankylosing spondylitis.
AB  - Neurological complications of ankylosing spondylitis (AS) are reported in 2.1% of
      patients. Cauda equina syndrome (CES) is rare and occurs at the ankylosing stage.
      MRI and CT of the lumbar spine show a cauda equina deformation with dural ectasia
      and bony erosion. We report three patients with AS presenting with progressive
      CES. These patients underwent lumboperitoneal shunting (LPS) surgery. The motor
      deficit improved in all cases. We suggest that CES develops from arterial
      pulsation of the CSF on a dural sac with reduced elasticity and that LPS reduces
      these intradural pressure shock waves. A meta-analysis by Ahn et al. [Ahn NU, Ahn
      UM, Nallamshetty L, et al. Cauda equina syndrome in ankylosing spondylitis (the
      CES-AS syndrome): meta-analysis of outcomes after medical and surgical
      treatments. J Spinal Disord 2001;14:427-33] concludes that surgical treatment has
      a better outcome than conservative or no treatment. Adding our 3 patients to this
      analysis, it appears that LPS for CES in AS is more efficient than laminectomy.
      LPS is a routine procedure for a rare indication, which promises improvement or
      atleast a stabilization of this disabling evolution of the disease.

PMID- 18710809
TI  - Acute hydrocephalus secondary to herpes simplex type II meningitis.
AB  - A 34-year-old woman presented with a rapid onset of meningitic symptoms.
      Cerebrospinal fluid (CSF) from a lumbar puncture revealed a leucocytosis with a
      preponderance of monocytes, elevated protein and reduced glucose. Herpes simplex
      virus (HSV) type II was subsequently confirmed by polymerase chain reaction (PCR)
      of CSF. The patient's level of consciousness deteriorated and a CT scan revealed
      hydrocephalus. The patient required placement of an external ventricular drain
      for 5 days; however, she made a full recovery without specific antiviral therapy.
      This is the first reported case of hydrocephalus secondary to isolated HSV type
      II meningitis.

PMID- 18710810
TI  - Exophytic intramedullary meningioma of the cervical spinal cord.
AB  - Intramedullary spinal cord neoplasms are relatively uncommon. The most common
      intramedullary tumors are astrocytomas and ependymomas. Meningiomas can occur as
      an intradural tumor; however, they are typically in the extramedullary
      compartment. A 42-year-old male presented with progressive sensory loss in the
      upper extremities and lower extremity weakness. Pre-operative imaging suggested
      an intramedullary cervical lesion. To treat the progressive neurological
      abnormality, surgical resection was planned. At surgery, it was noted that the
      tumor originated in the cervical spinal cord and extended into the extramedullary
      region. Histology confirmed the lesion to be a meningioma. This meningioma
      variant has not previously been described. Spinal meningiomas may occur in
      locations other than intradural, extramedullary locations, and should be included
      in the differential diagnosis of intramedullary lesions. Intramedullary
      meningiomas can be successfully treated with surgery.

PMID- 18710811
TI  - A rare anatomical variation of the C7 pedicle and intraspinal course of the C7
      nerve root.
AB  - We report a 58 year old man who presented with severe C7 radiculopathy which
      failed to respond to conservative measures. Subsequent CT and MR imaging of his
      cervical spine demonstrated C6/7 foraminal stenosis as well as unusual low take
      off of the C7 nerve root in relation to a congenital low-set C7 pedicle, findings
      which were subsequently confirmed intra-operatively. The relevance of the bony
      and neural anatomy is described and its implications for surgical management are
      discussed. To our knowledge, this anatomical anomaly has not been previously
      highlighted in the published English literature.

PMID- 18710812
TI  - Epidermoid cysts of the velum interpositum.
AB  - The cistern of the velum interpositum is a space located between the corpus
      callosum dorsally and the roof of the third ventricle ventrally. Lesions located
      within the velum interpositum are rare and include meningiomas, pilocytic
      astrocytomas, atypical teratoid/rhabdoid tumors and arachnoid cysts. Epidermoid
      cysts in this location have not been reported previously. We report the clinical
      and radiological features of two patients with epidermoid cysts located in the
      velum interpositum. The patients presented with gait difficulty and features of
      raised intracranial pressure and magnetic resonance imaging demonstrated large
      tumors in the velum interpositum with intensities suggestive of epidermoid cysts.
      There was ventral displacement of the internal cerebral veins and dorsal
      displacement of the corpus callosum in keeping with a mass in the velum
      interpositum. Tumors of the third ventricle displace the internal cerebral veins
      dorsally. A transcallosal approach was used in both patients to effectively
      excise the tumors.

PMID- 18710813
TI  - NO-donors. Part 17: Synthesis and antimicrobial activity of novel ketoconazole-NO
      donor hybrid compounds.
AB  - Novel hybrid compounds combining the antifungal drug ketoconazole with a diazen-1
      ium-1,2-diolate or an organic nitrate moiety and the corresponding NO-donors
      without ketoconazole were synthesized and their activities against a broad
      variety of fungal strains were tested. Hybridization modifies the spectrum of
      antimicrobial activities and generally, the ketoconazole-NO-donor hybrids are
      more potent than ketoconazole. The NO-donors alone show insufficient
      effectiveness.

PMID- 18710814
TI  - The use of microbeams to investigate radiation damage in living cells.
AB  - The micro-irradiation technique continues to be highly relevant to a number of
      radiobiological studies in vitro. In particular, studies of the bystander effect
      show that direct damage to cells is not the only trigger for radiation-induced
      effects, but that unirradiated cells can also respond to signals from irradiated
      neighbours. Furthermore, the bystander response can be initiated even when no
      energy is deposited in the genomic DNA of the irradiated cell (i.e. by targeting
      just the cytoplasm).

PMID- 18710815
TI  - Time-course evaluation and treatment of skin inflammatory immune response after
      ultraviolet B irradiation.
AB  - Skin exposure to high doses of ultraviolet B (UVB) radiation generates a severe
      inflammatory skin response. In the present study we aim to investigate, using in
      vitro and in vivo models, the time-course of the inflammatory skin immune
      response after an acute exposure to UVB irradiation, as well as its modulation by
      a topical non-steroidal anti-inflammatory drug (NSAID) treatment, naproxen. PGE2
      production and TNF-alpha levels increase in a post-irradiation time-dependent
      manner both in vivo and in vitro. This production pattern is also reflected in
      the iNOS expression levels in vivo and in the IL-6 levels in vitro. Changes
      observed in these mediators are correlated with histological alterations and
      dermal infiltration after the acute UVB irradiation. Naproxen treatment notably
      reduces PGE2 production and iNOS expression, reflecting the COX-NOS crosstalk
      already reported, although it causes an important increment in TNF-alpha
      synthesis in the epidermis of irradiated mice. Taken together, our data indicates
      that the epidermis is severely damaged by UVB radiation but then it is able to
      fully recover, and that the immune response is modulated by the NSAID treatment,
      since it is able to reduce the levels of some mediators as well as it can
      increase others.

PMID- 18710816
TI  - Spherical classification of wavelet transformed EMG intensity patterns.
AB  - Electromyograms of different muscles can be submitted to a wavelet-transform and
      arranged in a Multi-Muscle Pattern (MMP). The MMP represents the intensity of the
      EMG signals of a number of muscles simultaneously in time/frequency space. As
      previously shown, the MMPs can be represented by points in an Euclidian vector
      space that was called pattern space. The variability of the MMPs is represented
      by the distribution of the scattered points in pattern space. The purpose of this
      study was to investigate the distribution of the points and use the properties of
      the distribution to classify MMPs. The first task was to test whether the points
      representing a group of MMPs were located between the inner and outer boundary of
      a sphere-like domain in whitened pattern space as theoretically predicted. The
      mean of these points and thus of the MMPs is represented by a point at the center
      of the sphere. The hypothesis was that the spheres representing points of the
      MMPs of barefoot and shod runners were sufficiently separated and distinguishable
      in pattern space to allow classification of the runners according to their shod
      condition. The results confirmed the hypothesis and revealed that the recognition
      rate was over 80%. One can conclude and generalize that the points representing
      MMPs recorded for a certain condition reside between the inner and outer boundary
      of the sphere. The classification based on the spherical feature represents a
      much better discrimination than one based on the distance from the mean.

PMID- 18710817
TI  - Temporal summation of pressure pain during muscle hyperalgesia evoked by nerve
      growth factor and eccentric contractions.
AB  - Nerve growth factor (NGF) has a key role in the generation and potentiation of
      pain. Its centrally sensitizing effects may facilitate pain responses to noxious
      stimulus. This study assessed (1) the influence of NGF on delayed onset muscle
      soreness (DOMS) in shoulder muscles; and (2) the temporal summation of pressure
      pain during hyperalgesia induced by NGF and DOMS. In a blinded design, 10 healthy
      subjects were injected with NGF in the trapezius muscle on one side and with
      isotonic saline on the contralateral side as control. The subjects undertook
      shoulder eccentric exercise to induce DOMS in the shoulder muscles 3h after the
      injections. The soreness intensity to muscle contraction, pressure pain
      thresholds (PPT), and pain intensity to sequential stimuli (i.e. temporal
      summation at 1 and 30s inter-stimulus interval (ISI)) were assessed before
      injections - 3, 24h, and 4, 7, and 21 days after injections. The soreness
      intensity to muscle contraction significantly increased at 3 and 24h in both
      shoulders (P<0.05) and went back to baseline levels at day 7. The same
      development was seen in PPT as reduced thresholds (P<0.05). The NGF injected side
      had higher pain ratings during temporal summation at 1s ISI compared with the
      contralateral side 24h after injections. Intramuscular administration of NGF
      intensified the DOMS responses, evoking facilitated temporal summation. Central
      as well as peripheral sensitization mechanisms may play a role in the
      facilitation.

PMID- 18710819
TI  - Hypoxia induces resistance to 5-fluorouracil in oral cancer cells via G(1) phase
      cell cycle arrest.
AB  - Malignant tumors are exposed to various levels of hypoxic condition in vivo. It
      has been known that tumor cells under hypoxia are resistant to chemotherapies. To
      clarify the mechanism of the hypoxia-induced chemoresistance, we evaluated the
      effects of hypoxia on the resistance of oral squamous cell carcinoma (OSCC) cell
      lines to 5-fluorouracil (5-FU). OSCC cells were divided to two groups by the
      proliferation activity under hypoxic condition; hypoxia-resistant (HR) and
      hypoxia-sensitive (HS) cells. Growth of HS cells were inhibited by hypoxia and
      introduced to G(1) arrest in cell cycle. 5-FU effect on HS cell viability was
      markedly reduced in hypoxic condition without an induction of chemoresistant
      related protein, P-glycoprotein. However, proliferation, cell cycle, and 5-FU
      sensitivity of HR cells were not affected by hypoxia. Hypoxia-inducible factor
      (HIF)-1alpha was induced by hypoxia in all OSCC cell lines, but diminished in HS
      cells within 48h. Expression of p21 and p27 was strongly augmented and CyclinD
      expression was reduced by hypoxia in HS cells. However, the expression of these
      proteins was constitutive in HR cells during 48h hypoxic culture. Phosphorylation
      of mammalian target of rapamycin (mTOR) was reduced by hypoxia in HS cells. From
      these findings, we concluded that HS OSCC cells acquire 5-FU resistance under
      hypoxia by G(1)/S transition through an upregulation of cell cycle inhibitors.

PMID- 18710821
TI  - Pattern of lymph node metastases in squamous cell carcinoma of the tonsil:
      implication for selective neck dissection.
AB  - The aim of this study was to prospectively analyze the distribution of neck
      metastases and the outcome in patients surgically treated for tonsillar carcinoma
      in order to deduce implications for selective neck dissection. The criteria for
      inclusion in the study were (1) previously untreated, histologically proven,
      resectable squamous cell carcinoma of the tonsil, (2) curative surgical intent on
      the primary tumor and neck, (3) no history of prior head and neck cancer, (4)
      absence of synchronous second primary in the upper aerodigestive tract, lung and
      esophagus, (5) absence of distant metastases. Fifty-eight previously untreated
      consecutive patients with tonsillar squamous cell carcinoma were included in this
      prospective study. Among 22 patients with clinically negative cervical lymph
      nodes, 4 patients (18.2%) had metastatic lymph nodes on pathologic examination.
      Occult node metastases were mainly located in ipsilateral II level. No occult
      metastases occurred at levels I and V. Among 36 patients with clinically positive
      cervical lymph nodes, 3 patients (8.3%) had an occult pathologic metastatic
      involvement of cervical lymph nodes of ipsilateral level V. Level I was free of
      lymph node metastases. Clinical N category >N2a (p=0.003), nodal metastases to
      levels III (p=0.026) and IV (p=0.009) were significantly related to level V nodal
      metastases. The 2 and 5 years actuarial disease-free survival was 82.7% (95% CI
      71.2-93.5%) and 58.3% (95% CI 36.7-79.9%), respectively. The actuarial recurrence
      free survival was 87.9% (95% CI 78.9-96.8%) and 72.2% (95% CI 53.9-90.5%) at 2
      and 5 years, respectively. Our findings support the role of a selective lateral
      neck dissection in the management of clinically N0 necks and in selected N+ necks
      (N1 and N2a disease located at level II) in patients with tonsillar carcinoma
      without oral involvement.

PMID- 18710822
TI  - Quantitative and qualitative analysis of proteins in fresh frozen plasma obtained
      from whole blood donations and prepared with two photochemical treatments.
AB  - Thirty-six fresh frozen plasma (FFP) units obtained from whole blood donations
      were used for 12 replicate experiments. For each replicate experiment, three ABO
      matched FFP units were pooled and divided into three units containing different
      volumes of identical plasma. One unit was used as control FFP, one unit was
      treated with methylene blue plus visible light and one unit was treated with
      amotosalen and UVA light. The overall coagulation factor levels were better
      maintained in untreated FFP than in photochemically treated plasma. However,
      treated-plasma by both photochemical methods maintained coagulation factor levels
      that met or exceeded the European Pharmacopeia requirements for therapeutic
      plasma.

PMID- 18710823
TI  - What's happening--probing of HPA-1a antigen-antibody interaction by surface
      plasmon resonance technology.
AB  - This brief report summarizes the use of surface plasmon resonance technology
      (SPRT) in probing HPA-1a antigen-antibody interactions, based on a poster
      presented at the 60th meeting of the American Association of Blood Banks. It was
      concluded that the GP purification method could affect the performance of antigen
      in SPRT. It also highlighted that chips immobilised with Monoclonal antibody
      (Mab)-purified GP-IIb/IIIa work satisfactorily with both monoclonal and
      recombinant Abs with the appropriate concentration and binding affinity, while
      determination of the avidity and concentration of maternal polyclonal antibodies
      in respect to clinical severity on NAIT warrants further development.

PMID- 18710824
TI  - Mobile Schwannoma of the skin.

PMID- 18710818
TI  - Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models.
AB  - Animal models are fundamentally important in our quest to understand the genetic,
      epigenetic, and environmental factors that contribute to human aging. In
      comparison to humans, relatively short-lived mammals are useful models as they
      allow for rapid assessment of both genetic manipulation and environmental
      intervention as related to longevity. These models also allow for the study of
      clinically relevant pathologies as a function of aging. Data associated with more
      distant species offers additional insight and critical consideration of the basic
      physiological processes and molecular mechanisms that influence lifespan.
      Consistently, two interventions, caloric restriction and repression of the growth
      hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to
      increase lifespan in both invertebrates and vertebrate animal model systems.
      Caloric restriction (CR) is a nutrition intervention that robustly extends
      lifespan whether it is started early or later in life. Likewise, genes involved
      in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and
      invertebrates, implying evolutionary conservation of the molecular mechanisms.
      Specifically, insulin and insulin-like growth factor-1 (IGF-1)-like signaling and
      its downstream intracellular signaling molecules have been shown to be associated
      with lifespan in fruit flies and nematodes. More recently, mammalian models with
      reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have
      extended lifespans as compared to control siblings. Importantly, this research
      has also shown that these genetic alterations can keep the animals healthy and
      disease-free for longer periods and can alleviate specific age-related
      pathologies similar to what is observed for CR individuals. Thus, these mutations
      may not only extend lifespan but may also improve healthspan, the general health
      and quality of life of an organism as it ages. In this review, we will provide an
      overview of how the manipulation of the GH/IGF axis influences lifespan,
      highlight the invertebrate and vertebrate animal models with altered lifespan due
      to modifications to the GH/IGF-1 signaling cascade or homologous pathways, and
      discuss the basic phenotypic characteristics and healthspan of these models.

PMID- 18710825
TI  - Sexual dysfunction in newly diagnosed multiple sclerosis women.
AB  - OBJECTIVES: The aim of the study was to evaluate female sexuality in a selective
      population of newly diagnosed multiple sclerosis (MS) women. MATERIALS AND
      METHODS: In this clinic-based study, 63 newly diagnosed consecutive women
      affected by definite MS were admitted. Disability and depression were evaluated
      with the expanded disability status scale (EDSS) and Beck depression inventory,
      respectively. Sexual function was evaluated with the female sexual function index
      (FSFI). A group of 61 healthy female volunteers with the same baseline
      characteristics were used as controls. Postmenopausal women and patients with
      other major concomitant neurological, endocrinological, vascular, gynecological,
      psychiatric disorders, use of medicines that can cause female sexual dysfunction
      (FSD) and disease-modifying drugs were excluded from the study. RESULTS: All the
      evaluated patients were ambulant with no major neurological impairment (mean EDSS
      score 2.5, range 0-3.5). None of the patients were considered clinically
      depressed, but some of them were sad or worried. According to the sexual history
      and FSFI scores, sexual dysfunction was diagnosed in 22 (34.9%) out of the 63
      patients and in 13 (21.31%) out of the 61 healthy females (P > 0.05).
      CONCLUSIONS: In the newly diagnosed MS patients, FSD represent an important issue
      even though disability and other concomitant disorders affecting sexual function
      were excluded.

PMID- 18710828
TI  - Salt wars.

PMID- 18710826
TI  - Expression, purification and characterization of human PHD1 in Escherichia coli.
AB  - The hypoxia-inducible factors (HIFs) play a central role in oxygen homeostasis.
      HIF prolyl hydroxylases (PHDs) modify HIFalpha subunits and thereby target them
      for proteasomal degradation. Mammalian PHDs comprise three isozymes, PHD1, PHD2
      and PHD3, and belong to the iron(II)-2-oxoglutarate-dependent dioxygenase family.
      We have expressed full-length human PHD1 in Escherichia coli, and purified it to
      apparent homogeneity by immobilized Ni-affinity chromatography, cation-exchange
      HPLC followed by gel filtration. Fe(2+) was found to have EC(50) value of 0.64
      microM and the purified enzyme showed maximal activity at 10 microM Fe(2+). The
      IC(50) values for transition metal ions, Co(2+), Ni(2+) and Cu(2+), were 58, 35
      and 220 microM, respectively, in the presence of 100 microM Fe(2+). Mn(2+) did
      not affect the activity <1 mM. Many transcription-related proteins are regulated
      by phosphorylation. Thus, recombinant PHD1 was examined for in vitro
      phosphorylation using protein kinase A, protein kinase Calpha, casein kinase I
      and II and Erk2. The protein was most strongly phosphorylated by protein kinase
      Calpha, and the phosphorylation sites were found to be Ser-132, Ser-226 and Ser
      234. Mutation of Ser-132 or Ser-234 to Asp or Glu diminished the enzymatic
      activity to 25-60%, while mutation of Ser-226 scarcely influenced the activity.

PMID- 18710830
TI  - Wearable artificial kidneys...2008. What's new?

PMID- 18710831
TI  - ERA-EDTA--a dynamic association moving forward.

PMID- 18710833
TI  - Haematoma and abscess after epidural analgesia.

PMID- 18710834
TI  - NICE and warm.

PMID- 18710835
TI  - Cardiac surgery, cardiopulmonary bypass, and preoperative renal dysfunction.

PMID- 18710836
TI  - Renal oxygen delivery during cardiopulmonary bypass.

PMID- 18710837
TI  - Successful treatment with landiolol for the recurrence of significant ST-segment
      depression during early postoperative period.

PMID- 18710838
TI  - Debate about non-heart beating organ donation.

PMID- 18710839
TI  - Remifentanil obtunds intraocular pressure rises associated with suxamethonium.

PMID- 18710840
TI  - Magnetic resonance imaging of the spinal column.

PMID- 18710841
TI  - Effects of depth of isoflurane anaesthesia on a cognition task in mice.

PMID- 18710842
TI  - Human reproduction.

PMID- 18710843
TI  - Amyloidoma of the chest wall: a rare entity.
AB  - Amyloidoma (tumoral amyloidosis) is defined as a solitary localized tumor-like
      deposit of amyloid, in the absence of systemic amyloidosis. Amyloidoma is the
      least common presentation of tissue amyloid deposition, reported in many anatomic
      sites including the respiratory, genitourinary and gastrointestinal tracts, as
      well as the central nervous system, skin, breast and soft tissue. Amyloidoma of
      the chest wall is extremely rare, and to date only one case has been reported in
      literature. The authors present a case of a chest wall tumor that causes local
      destruction, being an amyloidoma on histopathologic examination. It was treated
      with wide local excision, with no recurrence during almost two years of follow
      up. A search for occult systemic disease is recommended and was also performed.

PMID- 18710844
TI  - Antibiotics for coughs and colds. Goodbye, virus.

PMID- 18710845
TI  - Antibiotics for coughs and colds. Hello, virus.

PMID- 18710846
TI  - Ethnic stereotypes and the underachievement of UK medical students from ethnic
      minorities: qualitative study.
AB  - OBJECTIVE: To explore ethnic stereotypes of UK medical students in the context of
      academic underachievement of medical students from ethnic minorities. DESIGN:
      Qualitative study using semistructured one to one interviews and focus groups.
      SETTING: A London medical school. PARTICIPANTS: 27 year 3 medical students and 25
      clinical teachers, purposively sampled for ethnicity and sex. METHODS: Data were
      analysed using the theory of stereotype threat (a psychological phenomenon
      thought to negatively affect the performance of people from ethnic minorities in
      educational contexts) and the constant comparative method. RESULTS: Participants
      believed the student-teacher relationship was vital for clinical learning.
      Teachers had strong perceptions about "good" clinical students (interactive,
      keen, respectful), and some described being aggressive towards students whom they
      perceived as quiet, unmotivated, and unwilling. Students had equally strong
      perceptions about "good" clinical teachers (encouraging, interested, interactive,
      non-aggressive). Students and teachers had concordant and well developed
      perceptions of the "typical" Asian clinical medical student who was considered
      over-reliant on books, poor at communicating with patients, too quiet during
      clinical teaching sessions, and unmotivated owing to being pushed into studying
      medicine by ambitious parents. Stereotypes of the "typical" white student were
      less well developed: autonomous, confident, and outgoing team player. Direct
      discrimination was not reported. CONCLUSIONS: Asian clinical medical students may
      be more likely than white students to be perceived stereotypically and
      negatively, which may reduce their learning by jeopardising their relationships
      with teachers. The existence of a negative stereotype about their group also
      raises the possibility that underperformance of medical students from ethnic
      minorities may be partly due to stereotype threat. It is recommended that
      clinical teachers be given opportunities and training to encourage them to get to
      know their students as individuals and thus foster positive educational
      relationships with them.

PMID- 18710847
TI  - Commentary: An "ethnic minority" medical student.

PMID- 18710848
TI  - Antibiotics for coughs and colds. Different in developing world.

PMID- 18710849
TI  - Intimate partner violence. Honesty is needed when assuring confidentiality.

PMID- 18710850
TI  - Violence between intimate partners knows no age limit.

PMID- 18710851
TI  - GPs under attack. Minerva should not perpetuate hearsay.

PMID- 18710852
TI  - GPs under attack. More negative spin.

PMID- 18710853
TI  - Are NICE stroke guidelines scientific or political?

PMID- 18710854
TI  - Hospitals should tell police about knife wounds, says GMC.

PMID- 18710855
TI  - How to prevent ICD shocks: part I.

PMID- 18710856
TI  - How to prevent ICD shocks: part II.

PMID- 18710857
TI  - Modulation of acute diarrheal illness by persistent bacterial infection.
AB  - Acute diarrheal illness is a global health problem that may be exacerbated by
      concurrent infection. Using Citrobacter rodentium, a murine model of attaching
      and effacing diarrheagenic Escherichia coli, we demonstrate that persistent
      Helicobacter hepaticus infection modulates host responses to diarrheal disease,
      resulting in delayed recovery from weight loss and from tissue damage. Chronic
      colitis in concurrently infected mice is characterized by macrophage and Foxp3(+)
      regulatory T-cell accumulation. Prolonged disease is also associated with
      increased interleukin-17 expression, which may be due to suppression of gamma
      interferon during the acute phase of diarrheal infection. This new model of
      polymicrobial infection provides insight into the mechanism by which subclinical
      infection can exacerbate morbidity due to an unrelated self-limiting infection.

PMID- 18710858
TI  - Prostaglandin E2 produced by Entamoeba histolytica binds to EP4 receptors and
      stimulates interleukin-8 production in human colonic cells.
AB  - Entamoeba histolytica pathogenesis in the colon occurs in a stepwise fashion. It
      begins with colonization of the mucin layer, which is followed by stimulation of
      a proinflammatory response that causes nonspecific tissue damage that may
      facilitate parasite invasion of the underlying colonic mucosa. Unfortunately, the
      parasite and/or host factors that stimulate a proinflammatory response in the gut
      are poorly understood. In this study, we found that live E. histolytica or
      secretory or proteins (SP) and soluble ameba components (SAP) can markedly
      increase interleukin-8 (IL-8) mRNA expression and protein production in colonic
      epithelial cells. The IL-8-stimulating molecule produced by live amebae was
      identified as prostaglandin E(2) (PGE(2)) as trophozoites treated with
      cyclooxygenase inhibitors inhibited the biosynthesis of PGE(2) and eliminated IL
      8 production induced by live parasites or ameba components. Moreover, using
      specific prostaglandin EP2 and EP4 receptor agonists and antagonists, we found
      that PGE(2) binds exclusively through EP4 receptors in colonic epithelial cells
      to stimulate IL-8 production. Silencing of EP4 receptors with EP4 small
      interfering RNA completely eliminated SP- and SAP-induced IL-8 production. These
      studies identified bioactive PGE(2) as a one of the major virulence factors
      produced by E. histolytica that can stimulate the potent neutrophil chemokine and
      activator IL-8, which can trigger an acute host inflammatory response. Thus, the
      induction of IL-8 production in response to E. histolytica-derived PGE(2) may be
      a mechanism that explains the initiation and amplification of acute inflammation
      associated with intestinal amebiasis.

PMID- 18710859
TI  - Coinfection with the intestinal nematode Heligmosomoides polygyrus markedly
      reduces hepatic egg-induced immunopathology and proinflammatory cytokines in
      mouse models of severe schistosomiasis.
AB  - Infection with the trematode helminth Schistosoma mansoni results in a parasite
      egg-induced, CD4 T-cell-mediated, hepatointestinal granulomatous and fibrosing
      inflammation that varies greatly in severity, with a higher frequency of milder
      forms typically occurring in regions where the disease is endemic. One possible
      explanation for this is that in these regions the degree of inflammation is
      lessened by widespread concurrent infection with gastrointestinal nematodes. We
      tested this hypothesis by establishing a murine coinfection model in which mice
      were infected with the intestinal nematode parasite Heligmosomoides polygyrus
      prior to infection with S. mansoni. In CBA mice that naturally display a severe
      form of schistosomiasis, preinfection with H. polygyrus resulted in a marked
      reduction in schistosome egg-induced hepatic immunopathology, which was
      associated with significant decreases in the levels of interleukin-17 (IL-17),
      gamma interferon, tumor necrosis factor alpha, IL-23, IL-6, and IL-1beta and with
      increases in the levels of IL-4, IL-5, IL-10, and transforming growth factor beta
      in mesenteric lymph node cells, purified CD4 T cells, and isolated liver
      granuloma cells. There also were increases in liver Ym1 and forkhead box P3
      transcription factor expression. In another model of high-pathology
      schistosomiasis induced in C57BL/6 mice by immunization with schistosome egg
      antigens in complete Freund's adjuvant, coinfection with the nematodes also
      resulted in a marked inhibition of hepatic immunopathology accompanied by similar
      shifts in cytokine production. These findings demonstrate that intestinal
      nematodes prevent Th1- and Th17-cell-mediated inflammation by promoting a strong
      Th2-polarized environment associated with increases in the levels of
      alternatively activated macrophages and T regulatory cells, which result in
      significant amelioration of schistosome-induced immunopathology.

PMID- 18710860
TI  - Mycobacterium bovis BCG immunization induces protective immunity against nine
      different Mycobacterium tuberculosis strains in mice.
AB  - Recent preclinical and epidemiologic studies have suggested that certain
      Mycobacterium tuberculosis genotypes (in particular, Beijing lineage strains) may
      be resistant to Mycobacterium bovis BCG vaccine-induced antituberculosis
      protective immunity. To investigate the strain specificity of BCG-induced
      protective responses in a murine model of pulmonary tuberculosis, C57BL/6 mice
      were vaccinated with BCG vaccine and then challenged 2 months later with one of
      nine M. tuberculosis isolates. Four of these strains were from the W-Beijing
      lineage (HN878, N4, NHN5, and ChS) while four were non-Beijing-type isolates
      (C913, CDC1551, NY669, and NY920). As a control, the WHO standard M. tuberculosis
      Erdman strain was evaluated in these vaccination/challenge experiments. To assess
      the protective responses evoked by BCG immunization, organ bacterial burdens and
      lung pathology were assessed in vaccinated and naive mice at 4, 12, and 20 weeks
      postchallenge as well as during the day of infection. At 4 weeks after the
      aerosol challenge with each of these strains, significantly reduced bacterial
      growth in the lungs and spleens and significantly improved lung pathology were
      seen in all vaccinated animals compared to naive controls. After 12 weeks,
      reduced organ bacterial burdens were detected in vaccinated animals infected with
      six of nine challenge strains. Although lung CFU values were lower in vaccinated
      mice for only three of nine groups at 20 weeks postchallenge, significantly
      decreased lung inflammation was seen in all immunized animals relative to
      controls at 20 weeks postchallenge. Taken together, these data demonstrate that
      BCG vaccination protects against infection with diverse M. tuberculosis strains
      in the mouse model of pulmonary tuberculosis and suggest that strain-specific
      resistance to BCG-induced protective immunity may be uncommon.

PMID- 18710861
TI  - Shr is a broad-spectrum surface receptor that contributes to adherence and
      virulence in group A streptococcus.
AB  - Group A streptococcus (GAS) is a common hemolytic pathogen that produces a range
      of suppurative infections and autoimmune sequelae in humans. Shr is an exported
      protein in GAS, which binds in vitro to hemoglobin, myoglobin, and the hemoglobin
      haptoglobin complex. We previously reported that Shr is found in association with
      whole GAS cells and in culture supernatant. Here, we demonstrate that cell
      associated Shr could not be released from the bacteria by the muralytic enzyme
      mutanolysin and was instead localized to the membrane. Shr was available,
      however, on the exterior of GAS, exposed to the extracellular environment. In
      vitro binding and competition assays demonstrated that in addition to hemoprotein
      binding, purified Shr specifically interacts with immobilized fibronectin and
      laminin. The absence of typical fibronectin-binding motifs indicates that a new
      protein pattern is involved in the binding of Shr to the extracellular matrix.
      Recombinant Lactococcus lactis cells expressing Shr on the bacterial surface
      gained the ability to bind to immobilized fibronectin, suggesting that Shr can
      function as an adhesin. The inactivation of shr resulted in a 40% reduction in
      the attachment to human epithelial cells in comparison to the parent strain. GAS
      infection elicited a high titer of Shr antibodies in sera from convalescent mice,
      demonstrating that Shr is expressed in vivo. The shr mutant was attenuated for
      virulence in an intramuscular zebrafish model system. In summary, this study
      identifies Shr as being a new microbial surface component recognizing adhesive
      matrix molecules in GAS that mediates attachment to epithelial cells and
      contributes to the infection process.

PMID- 18710862
TI  - CcpA mediates the catabolite repression of tst in Staphylococcus aureus.
AB  - Some clinical isolates of Staphylococcus aureus produce the superantigenic toxic
      shock syndrome toxin 1 (TSST-1), encoded by tst, located on pathogenicity
      islands. The expression of tst is complex and is influenced by environmental
      conditions such as pH, CO(2), and glucose. We identified a putative catabolite
      responsive element (cre) in the promoter regions of all known tst genes,
      indicating that tst transcription may be regulated by the catabolite control
      protein CcpA. By introducing tst genes under the control of their native
      promoters or tst promoter-reporter gene fusions in wild-type strain Newman, we
      showed that glucose was able to repress tst transcription and TSST-1 production,
      whereas glucose repression was abolished in the corresponding Delta ccpA mutant.
      Stabilizing the pH ruled out a pH effect due to acid production during glucose
      catabolism. CcpA thus directly regulates tst transcription, linking carbohydrate
      utilization to virulence gene expression in S. aureus.

PMID- 18710863
TI  - The cyclic AMP receptor protein, CRP, is required for both virulence and
      expression of the minimal CRP regulon in Yersinia pestis biovar microtus.
AB  - The cyclic AMP receptor protein (CRP) is a bacterial regulator that controls more
      than 100 promoters, including those involved in catabolite repression. In the
      present study, a null deletion of the crp gene was constructed for Yersinia
      pestis bv. microtus strain 201. Microarray expression analysis disclosed that at
      least 6% of Y. pestis genes were affected by this mutation. Further reverse
      transcription-PCR and electrophoretic mobility shift assay analyses disclosed a
      set of 37 genes or putative operons to be the direct targets of CRP, and thus
      they constitute the minimal CRP regulon in Y. pestis. Subsequent primer extension
      and DNase I footprinting assays mapped transcriptional start sites, core promoter
      elements, and CRP binding sites within the DNA regions upstream of pla and pst,
      revealing positive and direct control of these two laterally acquired plasmid
      genes by CRP. The crp disruption affected both in vitro and in vivo growth of the
      mutant and led to a >15,000-fold loss of virulence after subcutaneous infection
      but a <40-fold increase in the 50% lethal dose by intravenous inoculation.
      Therefore, CRP is required for the virulence of Y. pestis and, particularly, is
      more important for infection by subcutaneous inoculation. It can further be
      concluded that the reduced in vivo growth phenotype of the crp mutant should
      contribute, at least partially, to its attenuation of virulence by both routes of
      infection. Consistent with a previous study of Y. pestis bv. medievalis, lacZ
      reporter fusion analysis indicated that the crp deletion resulted in the almost
      absolute loss of pla promoter activity. The plasminogen activator encoded by pla
      was previously shown to specifically promote Y. pestis dissemination from
      peripheral infection routes (subcutaneous infection [flea bite] or inhalation).
      The above evidence supports the notion that in addition to the reduced in vivo
      growth phenotype, the defect of pla expression in the crp mutant will greatly
      contribute to the huge loss of virulence of this mutant strain in subcutaneous
      infection.

PMID- 18710864
TI  - Identification and characterization of two novel staphylococcal enterotoxins,
      types S and T.
AB  - In addition to two known staphylococcal enterotoxin-like genes (selj and selr),
      two novel genes coding for two superantigens, staphylococcal enterotoxins S and T
      (SES and SET), were identified in plasmid pF5, which is harbored by food
      poisoning-related Staphylococcus aureus strain Fukuoka 5. This strain was
      implicated in a food poisoning incident in Fukuoka City, Japan, in 1997.
      Recombinant SES (rSES) specifically stimulated human T cells in a T-cell receptor
      Vbeta9- and Vbeta16-specific manner in the presence of major histocompatibility
      complex (MHC) class II(+) antigen-presenting cells (APC). rSET also stimulated T
      cells in the presence of MHC class II(+) APC, although its Vbeta skewing was not
      found in reactive T cells. Subsequently, we examined the emetic activity of SES
      and SET. We also studied SElR to determine emetic activity in primates. This
      toxin was identified in previous studies but was not examined in terms of
      possession of emetic activity for primates. rSES induced emetic reactions in two
      of four monkeys at a dose of 100 microg/kg within 5 h of intragastric
      administration. In one monkey, rSET induced a delayed reaction (24 h
      postadministration) at a dose of 100 microg/kg, and in the other one, the
      reaction occurred 5 days postadministration. rSElR induced a reaction in two of
      six animals within 5 h at 100 microg/kg. On this basis, we speculate that the
      causative toxins of vomiting in the Fukuoka case are SES and SER. Additionally,
      SES, SER, and SET also induced emesis in house musk shrews as in the monkeys.

PMID- 18710865
TI  - Identification and characterization of the Plasmodium yoelii PyP140/RON4 protein,
      an orthologue of Toxoplasma gondii RON4, whose cysteine-rich domain does not
      protect against lethal parasite challenge infection.
AB  - Previously, we identified a Plasmodium yoelii YM 140-kDa merozoite protein,
      designated PyP140, which formed a complex with apical membrane antigen 1 (AMA1).
      Furthermore, we produced a nonprotective monoclonal antibody (MAb), 48F8, that
      immunoprecipitated metabolically labeled PyP140 and localized the protein to the
      merozoite's apical end and, less frequently, to the merozoite surface, as
      observed by immunofluorescence assay (IFA). Here, using MAb 48F8, we have
      identified the pyp140 gene by screening a P. yoelii lambda-Zap cDNA expression
      library. The pyp140 cDNA covers approximately 90% of the putative open reading
      frame (ORF) of PY02159 from the P. yoelii NL genome sequencing project. Analysis
      of the complete gene identified the presence of two introns. The ORF encodes a
      102,407-Da protein with an amino-terminal signal sequence, a series of three
      unique types of repeats, and a cysteine-rich region. The binding site of MAb 48F8
      was also identified. A BLAST search with the deduced amino acid sequence shows
      significant similarity with the Toxoplasma gondii RON4 protein and the Plasmodium
      falciparum RON4 protein, and the sequence is highly conserved in other Plasmodium
      species. We produced the cysteine-rich domain of PyP140/RON4 by using the Pichia
      pastoris expression system and characterized the recombinant protein
      biochemically and biophysically. BALB/c mice immunized with the protein
      formulated in oil-in-water adjuvants produced antibodies that recognize
      parasitized erythrocytes by IFA and native PyP140/RON4 by immunoblotting but
      failed to protect against a lethal P. yoelii YM infection. Our results show that
      PyP140/RON4 is located within the rhoptries or micronemes. It may associate in
      part with AMA1, but the conserved cysteine-rich domain does not appear to elicit
      inhibitory antibodies, a finding that is supported by the marked sequence
      conservation in this protein within Plasmodium spp., suggesting that it is not
      under immune pressure.

PMID- 18710866
TI  - Chlamydial effector proteins localized to the host cell cytoplasmic compartment.
AB  - Disease-causing microbes utilize various strategies to modify their environment
      in order to create a favorable location for growth and survival. Gram-negative
      bacterial pathogens often use specialized secretion systems to translocate
      effector proteins directly into the cytosol of the eukaryotic cells they infect.
      These bacterial proteins are responsible for modulating eukaryotic cell
      functions. Identification of the bacterial effectors has been a critical step
      toward understanding the molecular basis for the pathogenesis of the bacteria
      that use them. Chlamydiae are obligate intracellular bacterial pathogens that
      have a type III secretion system believed to translocate virulence effector
      proteins into the cytosol of their host cells. Selective permeabilization of the
      eukaryotic cell membrane was used in conjunction with metabolic labeling of
      bacterial proteins to identify chlamydial proteins that localize within the
      cytosol of infected cells. More than 20 Chlamydia trachomatis and C. pneumoniae
      proteins were detected within the cytoplasmic compartment of infected cells.
      While a number of cytosolic proteins were shared, others were unique to each
      species, suggesting that variation among cytosolic chlamydial proteins
      contributes to the differences in the pathogenesis of the chlamydial species. The
      spectrum of chlamydial proteins exported differed concomitant with the progress
      of the developmental cycle. These data confirm that a dynamic relationship exists
      between Chlamydia and its host and that translocation of bacterial proteins into
      the cytosol is developmentally dependent.

PMID- 18710867
TI  - Enhanced Toll-like receptor responsiveness associated with mitogen-activated
      protein kinase activation in Plasmodium falciparum-infected children.
AB  - Acute Plasmodium falciparum infection is associated with strongly upregulated
      cytokine responses that are at least partly the result of activation of Toll-like
      receptors (TLRs). Whether and how TLR expression/responsiveness changes upon
      malarial infection is, however, currently not well understood. To assess this, we
      examined expression of TLRs and used the TLR ligand lipopolysaccharide (LPS) and
      Pam(3)Cys to stimulate peripheral blood mononuclear cells (PBMCs) from Ghanaian
      schoolchildren who live in a rural area where P. falciparum is endemic.
      Expression of TLR2 was higher, and responses to its ligand, Pam(3)Cys, were
      enhanced in P. falciparum-infected children compared to their uninfected
      counterparts. In cells from the same children, stimulation by Pam(3)Cys resulted
      in higher p38 mitogen-activated protein kinase activation and higher cytokine
      production. In vitro experiments confirmed that preincubation of PBMCs with P.
      falciparum-infected red blood cells enhanced responsiveness to TLR ligands. Taken
      together, the data indicate that P. falciparum-infected children in areas where
      malaria is endemic have an altered innate immune system, which might be important
      for the balance between immunity and pathology when new infections are
      encountered or when novel vaccines are introduced.

PMID- 18710868
TI  - ADP-ribosylation of actin by the Clostridium botulinum C2 toxin in mammalian
      cells results in delayed caspase-dependent apoptotic cell death.
AB  - The binary C2 toxin from Clostridium botulinum mono-ADP-ribosylates G-actin in
      the cytosol of eukaryotic cells. This modification leads to depolymerization of
      actin filaments accompanied by cell rounding within 3 h of incubation but does
      not immediately induce cell death. Here we investigated the long-term responses
      of mammalian cell lines (HeLa and Vero) following C2 toxin treatment. Cells
      stayed round even though the toxin was removed from the medium after its
      internalization into the cells. No unmodified actin reappeared in the C2 toxin
      treated cells within 48 h. Despite actin being completely ADP-ribosylated after
      about 7 h, no obvious decrease in the overall amount of actin was observed for at
      least 48 h. Therefore, ADP-ribosylation was not a signal for an accelerated
      degradation of actin in the tested cell lines. C2 toxin treatment resulted in
      delayed apoptotic cell death that became detectable about 15 to 24 h after toxin
      application in a portion of the cells. Poly(ADP)-ribosyltransferase 1 (PARP-1)
      was cleaved in C2 toxin-treated cells, an indication of caspase 3 activation and
      a hallmark of apoptosis. Furthermore, specific caspase inhibitors prevented C2
      toxin-induced apoptosis, implying that caspases 8 and 9 were activated in C2
      toxin-treated cells. C2I, the ADP-ribosyltransferase component of the C2 toxin,
      remained active in the cytosol for at least 48 h, and no extensive degradation of
      C2I was observed. From our data, we conclude that the long-lived nature of C2I in
      the host cell cytosol was essential for the nonreversible cytotoxic effect of C2
      toxin, resulting in delayed apoptosis of the tested mammalian cells.

PMID- 18710869
TI  - PapX, a P fimbrial operon-encoded inhibitor of motility in uropathogenic
      Escherichia coli.
AB  - Motility and adherence are two integral aspects of bacterial pathogenesis.
      Adherence, often mediated by fimbriae, permits bacteria to attach to host cells
      and establish infection, whereas flagellum-driven motility allows bacteria to
      disseminate to sites more advantageous for colonization. Both fimbriae and
      flagella have been proven important for virulence of uropathogenic Escherichia
      coli (UPEC). Reciprocal regulation is one mechanism by which bacteria may
      reconcile the contradictory actions of adherence and motility. PapX, a P fimbrial
      gene product of UPEC strain CFT073, is a functional homolog of MrpJ of Proteus
      mirabilis; ectopic expression of papX in P. mirabilis reduces motility. To define
      the connection between P fimbria expression and motility in UPEC, the role of
      papX in the regulation of motility of strain CFT073 was examined. Overexpression
      of papX decreased motility of CFT073, which correlated with both a significant
      reduction in flagellin protein synthesized and flagella assembled on the cell
      surface. Conversely, an increase in motility and flagellin production was seen in
      an isogenic papX deletion mutant of CFT073. Microarray and quantitative reverse
      transcription-PCR analysis indicated that repression of motility of CFT073 by
      PapX appears to occur at the transcriptional level; expression of many motility
      associated genes, including flhDC, the master regulator of motility, is decreased
      when papX is overexpressed. Transcription of motility genes is increased in the
      papX mutant compared to wild type. Electrophoretic mobility gel shift analysis
      revealed that PapX binds to the flhD promoter. We conclude that synthesis of P
      fimbriae regulates flagellum synthesis to repress motility via PapX.

PMID- 18710871
TI  - Markov model plus k-word distributions: a synergy that produces novel statistical
      measures for sequence comparison.
AB  - MOTIVATION: Many proposed statistical measures can efficiently compare biological
      sequences to further infer their structures, functions and evolutionary
      information. They are related in spirit because all the ideas for sequence
      comparison try to use the information on the k-word distributions, Markov model
      or both. Motivated by adding k-word distributions to Markov model directly, we
      investigated two novel statistical measures for sequence comparison, called
      wre.k.r and S2.k.r. RESULTS: The proposed measures were tested by similarity
      search, evaluation on functionally related regulatory sequences and phylogenetic
      analysis. This offers the systematic and quantitative experimental assessment of
      our measures. Moreover, we compared our achievements with these based on
      alignment or alignment-free. We grouped our experiments into two sets. The first
      one, performed via ROC (receiver operating curve) analysis, aims at assessing the
      intrinsic ability of our statistical measures to search for similar sequences
      from a database and discriminate functionally related regulatory sequences from
      unrelated sequences. The second one aims at assessing how well our statistical
      measure is used for phylogenetic analysis. The experimental assessment
      demonstrates that our similarity measures intending to incorporate k-word
      distributions into Markov model are more efficient.

PMID- 18710872
TI  - spolTools: online utilities for analyzing spoligotypes of the Mycobacterium
      tuberculosis complex.
AB  - spolTools is a collection of online programs designed to manipulate and analyze
      spoligotype datasets of the Mycobacterium tuberculosis complex. These tools are
      integrated into a repository currently containing 1179 spoligotypes and 6278
      isolates across 30 datasets. Users can search this database to export for
      external use or to pass on to the integrated tools. These tools include the
      computation of basic population genetic quantities, the visualization of clusters
      of spoligotype patterns based on an estimated evolutionary history and a
      procedure to predict emerging strains - genotypes associated with elevated
      transmission.

PMID- 18710870
TI  - Total, membrane, and immunogenic proteomes of macrophage- and tick cell-derived
      Ehrlichia chaffeensis evaluated by liquid chromatography-tandem mass spectrometry
      and MALDI-TOF methods.
AB  - Ehrlichia chaffeensis, a tick-transmitted rickettsial, is the causative agent of
      human monocytic ehrlichiosis. To examine protein expression patterns, we analyzed
      total, membrane, and immunogenic proteomes of E. chaffeensis originating from
      macrophage and tick cell cultures. Total proteins resolved by one-dimensional gel
      electrophoresis and subjected to liquid chromatography-electrospray ionization
      ion trap mass spectrometry allowed identification of 134 and 116 proteins from
      macrophage- and tick cell-derived E. chaffeensis, respectively. Because a
      majority of immunogenic proteins remained in the membrane fraction, individually
      picked total and immunogenic membrane proteins were also surveyed by liquid
      chromatography-tandem mass spectrometry and matrix-assisted laser desorption
      ionization-time of flight methods. The analysis aided the identification of 48
      additional proteins. In all, 278 genes of the E. chaffeensis genome were verified
      as functional genes. They included genes for DNA and protein metabolism, energy
      metabolism and transport, membrane proteins, hypothetical proteins, and many
      novel proteins of unknown function. The data reported in this study suggest that
      the membrane of E. chaffeensis is very complex, having many expressed proteins.
      This study represents the first and the most comprehensive analysis of E.
      chaffeensis-expressed proteins. This also is the first study confirming the
      expression of nearly one-fourth of all predicted genes of the E. chaffeensis
      genome, validating that they are functionally active genes, and demonstrating
      that classic shotgun proteomic approaches are feasible for tick-transmitted
      intraphagosomal bacteria. The identity of novel expressed proteins reported in
      this study, including the large selection of membrane and immunogenic proteins,
      will be valuable in elucidating pathogenic mechanisms and developing effective
      prevention and control methods.

PMID- 18710873
TI  - Inference of structure in subdivided populations at low levels of genetic
      differentiation--the correlated allele frequencies model revisited.
AB  - MOTIVATION: This article considers the problem of estimating population genetic
      subdivision from multilocus genotype data. A model is considered to make use of
      genotypes and possibly of spatial coordinates of sampled individuals. A
      particular attention is paid to the case of low genetic differentiation with the
      help of a previously described Bayesian clustering model where allele frequencies
      are assumed to be a priori correlated. Under this model, various problems of
      inference are considered, in particular the common and difficult, but still
      unaddressed, situation where the number of populations is unknown. RESULTS: A
      Markov chain Monte Carlo algorithm and a new post-processing scheme are proposed.
      It is shown that they significantly improve the accuracy of previously existing
      algorithms in terms of estimated number of populations and estimated population
      membership. This is illustrated numerically with data simulated from the prior
      likelihood model used in inference and also with data simulated from a Wright
      Fisher model. Improvements are also illustrated on a real dataset of eighty-eight
      wolverines (Gulo gulo) genotyped at 10 microsatellites loci. The interest of the
      solutions presented here are not specific to any clustering model and are hence
      relevant to many settings in populations genetics where weakly differentiated
      populations are assumed or sought. AVAILABILITY: The improvements implemented
      will be made available in version 3.0.0 of the R package Geneland. Informations
      on how to get and use the software are available from
      http://folk.uio.no/gillesg/Geneland.html. SUPPLEMENTARY INFORMATION:
      http://folk.uio.no/gillesg/CFM/SuppMat.pdf.

PMID- 18710874
TI  - Integrating expression data with domain interaction networks.
AB  - Recent studies have revealed that alternative splicing plays an important role in
      the observed protein and interaction diversity. Special microarrays allow for
      measuring gene expression at the exon level and thus for studying alternative
      transcripts and their corresponding protein domain architecture. We have
      developed the Cytoscape plugin DomainGraph that enables the visualization and
      detailed study of domain-domain interactions forming protein interaction
      networks. In addition, the integration of exon expression data supports the
      analysis of alternative splicing events and the characterization of their effects
      on the protein and domain interaction network. Different expression patterns
      between human tissues or cells can be identified by comparing the generated
      domain graphs. AVAILABILITY: The plugin DomainGraph and the online documentation
      are available at http://domaingraph.bioinf.mpi-inf.mpg.de.

PMID- 18710875
TI  - Accurate sequence-based prediction of catalytic residues.
AB  - MOTIVATION: Prediction of catalytic residues provides useful information for the
      research on function of enzymes. Most of the existing prediction methods are
      based on structural information, which limits their use. We propose a sequence
      based catalytic residue predictor that provides predictions with quality
      comparable to modern structure-based methods and that exceeds quality of state-of
      the-art sequence-based methods. RESULTS: Our method (CRpred) uses sequence-based
      features and the sequence-derived PSI-BLAST profile. We used feature selection to
      reduce the dimensionality of the input (and explain the input) to support vector
      machine (SVM) classifier that provides predictions. Tests on eight datasets and
      side-by-side comparison with six modern structure- and sequence-based predictors
      show that CRpred provides predictions with quality comparable to current
      structure-based methods and better than sequence-based methods. The proposed
      method obtains 15-19% precision and 48-58% TP (true positive) rate, depending on
      the dataset used. CRpred also provides confidence values that allow selecting a
      subset of predictions with higher precision. The improved quality is due to newly
      designed features and careful parameterization of the SVM. The features
      incorporate amino acids characterized by the highest and the lowest propensities
      to constitute catalytic residues, Gly that provides flexibility for catalytic
      sites and sequence motifs characteristic to certain catalytic reactions. Our
      features indicate that catalytic residues are on average more conserved when
      compared with the general population of residues and that highly conserved amino
      acids characterized by high catalytic propensity are likely to form catalytic
      sites. We also show that local (with respect to the sequence) hydrophobicity
      contributes towards the prediction.

PMID- 18710876
TI  - Optimal contact map alignment of protein-protein interfaces.
AB  - The long-standing problem of constructing protein structure alignments is of
      central importance in computational biology. The main goal is to provide an
      alignment of residue correspondences, in order to identify homologous residues
      across chains. A critical next step of this is the alignment of protein complexes
      and their interfaces. Here, we introduce the program CMAPi, a two-dimensional
      dynamic programming algorithm that, given a pair of protein complexes, optimally
      aligns the contact maps of their interfaces: it produces polynomial-time near
      optimal alignments in the case of multiple complexes. We demonstrate the efficacy
      of our algorithm on complexes from PPI families listed in the SCOPPI database and
      from highly divergent cytokine families. In comparison to existing techniques,
      CMAPi generates more accurate alignments of interacting residues within families
      of interacting proteins, especially for sequences with low similarity. While
      previous methods that use an all-atom based representation of the interface have
      been successful, CMAPi's use of a contact map representation allows it to be more
      tolerant to conformational changes and thus to align more of the interaction
      surface. These improved interface alignments should enhance homology modeling and
      threading methods for predicting PPIs by providing a basis for generating
      template profiles for sequence-structure alignment.

PMID- 18710877
TI  - A kindred with cerebellar ataxia and thermoanalgesia.
AB  - OBJECTIVE: To characterise the clinical, neurophysiological, neuropathological
      and genetic features of a family with cerebellar autosomal dominant ataxia.
      DESIGN: Patients were submitted to clinical, neuroradiological and
      neurophysiological examinations. Molecular studies were undertaken to exclude
      SCAs 1-3, 6-8, 12 and 17. Studies were performed to rule out linkage to SCA4 on
      chromosome 16, and for all still uncharacterised SCA loci. Neuropathological
      examination of the proband was performed with immunocytochemistry. RESULTS: These
      patients presented a late onset cerebellar ataxia with thermoanalgesia and deep
      sensory loss. Unlike in SCA4, reflexes were preserved. MRI revealed cerebellar,
      medullar and spinal cord atrophy. Neurophysiological studies showed absence or
      marked reduction of the sensory nerve action potentials and somatosensory evoked
      potentials in lower and upper limbs but preservation of the soleus H reflex. No
      triplet repeat expansion mutations in the studied SCA genes were identified. Our
      studies ruled out linkage of the disease to the SCA4 locus on chromosome 16 and
      the remaining reported SCA loci. The neuropathological study of the proband
      revealed severe loss of Purkinje cells and dentate neurons. The inferior olive
      and lower cranial nerve nuclei also showed extensive cell loss. Posterior columns
      and spinocerebellar tracts were demyelinated. Ubiquitin immunoreactive
      intranuclear inclusions were absent. CONCLUSION: This kind of cerebellar ataxia,
      associated with thermoanalgesia as well as deep sensory loss with retained
      reflexes, does not associate to any known SCA loci. Therefore, we identify and
      describe a new form of late onset dominant spinocerebellar ataxia.

PMID- 18710878
TI  - Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative
      phosphorylation.
AB  - AIMS: Mitochondrial dysfunction is a major factor in heart failure (HF). A
      pronounced variability of mitochondrial electron transport chain (ETC) defects is
      reported to occur in severe acquired cardiomyopathies without a consistent trend
      for depressed activity or expression. The aim of this study was to define the
      defect in the integrative function of cardiac mitochondria in coronary
      microembolization-induced HF. METHODS AND RESULTS: Studies were performed in the
      canine coronary microembolization-induced HF model of moderate severity.
      Oxidative phosphorylation was assessed as the integrative function of
      mitochondria, using a comprehensive variety of substrates in order to investigate
      mitochondrial membrane transport, dehydrogenase activity and electron-transport
      coupled to ATP synthesis. The supramolecular organization of the mitochondrial
      ETC also was investigated by native gel electrophoresis. We found a dramatic
      decrease in ADP-stimulated respiration that was not relieved by an uncoupler.
      Moreover, the ADP/O ratio was normal, indicating no defect in the phosphorylation
      apparatus. The data point to a defect in oxidative phosphorylation within the
      ETC. However, the individual activities of ETC complexes were normal. The amount
      of the supercomplex consisting of complex I/complex III dimer/complex IV, the
      major form of respirasome considered essential for oxidative phosphorylation, was
      decreased. CONCLUSIONS: We propose that the mitochondrial defect lies in the
      supermolecular assembly rather than in the individual components of the ETC.

PMID- 18710879
TI  - Change in the z-axis location of the sternal notch in an arms-raised vs arms-down
      position on CT examinations.
AB  - The aim of the study was to determine whether the sternal notch changes in its z
      axis position in the arms raised vs arms down position on CT scans. A
      retrospective study was made of 132 consecutive CT scans of the neck and chest.
      We recorded the table position of the sternal notch and the most inferior slice
      through the thyroid gland on both scans, and the table position on the chest CT
      where the configuration of the head and neck vessels most closely corresponded to
      their configuration on the sternal notch slice of the neck CT. The sternal notch
      moved up an average of 8.4 mm (p<0.0001) when the arms were raised. In 44 cases
      (33.3%), the sternal notch moved up by > or =10 mm. In 6% of cases, the sternal
      notch moved upwards > or =20 mm. There was a slightly greater upward movement of
      the sternum in males of 2.57 mm (p = 0.0208). Mean upward motion of the sternal
      notch relative to the vessels was 7.74 mm (p<0.0001). Mean upward motion of the
      sternal notch relative to the thyroid was 8.98 mm (p<0.0001). In conclusion, the
      sternal notch moves upwards relative to the CT table and soft tissues in the neck
      and upper mediastinum when the arms are raised; the degree of upward motion is
      greater in males. This may have implications when categorizing nodes at the
      cervicothoracic junction on staging CT examinations, when deciding if nodes might
      be accessible to ultrasound-guided biopsy, and in classifying goitres.

PMID- 18710880
TI  - NAIMA: target amplification strategy allowing quantitative on-chip detection of
      GMOs.
AB  - We have developed a novel multiplex quantitative DNA-based target amplification
      method suitable for sensitive, specific and quantitative detection on microarray.
      This new method named NASBA Implemented Microarray Analysis (NAIMA) was applied
      to GMO detection in food and feed, but its application can be extended to all
      fields of biology requiring simultaneous detection of low copy number DNA
      targets. In a first step, the use of tailed primers allows the multiplex
      synthesis of template DNAs in a primer extension reaction. A second step of the
      procedure consists of transcription-based amplification using universal primers.
      The cRNA product is further on directly ligated to fluorescent dyes labelled 3DNA
      dendrimers allowing signal amplification and hybridized without further
      purification on an oligonucleotide probe-based microarray for multiplex
      detection. Two triplex systems have been applied to test maize samples containing
      several transgenic lines, and NAIMA has shown to be sensitive down to two target
      copies and to provide quantitative data on the transgenic contents in a range of
      0.1-25%. Performances of NAIMA are comparable to singleplex quantitative real
      time PCR. In addition, NAIMA amplification is faster since 20 min are sufficient
      to achieve full amplification.

PMID- 18710881
TI  - Studying copy number variations using a nanofluidic platform.
AB  - Copy number variations (CNVs) in the human genome are conventionally detected
      using high-throughput scanning technologies, such as comparative genomic
      hybridization and high-density single nucleotide polymorphism (SNP) microarrays,
      or relatively low-throughput techniques, such as quantitative polymerase chain
      reaction (PCR). All these approaches are limited in resolution and can at best
      distinguish a twofold (or 50%) difference in copy number. We have developed a new
      technology to study copy numbers using a platform known as the digital array, a
      nanofluidic biochip capable of accurately quantitating genes of interest in DNA
      samples. We have evaluated the digital array's performance using a model system,
      to show that this technology is exquisitely sensitive, capable of differentiating
      as little as a 15% difference in gene copy number (or between 6 and 7 copies of a
      target gene). We have also analyzed commercial DNA samples for their CYP2D6 copy
      numbers and confirmed that our results were consistent with those obtained
      independently using conventional techniques. In a screening experiment with
      breast cancer and normal DNA samples, the ERBB2 gene was found to be amplified in
      about 35% of breast cancer samples. The use of the digital array enables accurate
      measurement of gene copy numbers and is of significant value in CNV studies.

PMID- 18710882
TI  - Prioritization of candidate cancer genes--an aid to oncogenomic studies.
AB  - The development of techniques for oncogenomic analyses such as array comparative
      genomic hybridization, messenger RNA expression arrays and mutational screens
      have come to the fore in modern cancer research. Studies utilizing these
      techniques are able to highlight panels of genes that are altered in cancer.
      However, these candidate cancer genes must then be scrutinized to reveal whether
      they contribute to oncogenesis or are coincidental and non-causative. We present
      a computational method for the prioritization of candidate (i) proto-oncogenes
      and (ii) tumour suppressor genes from oncogenomic experiments. We constructed
      computational classifiers using different combinations of sequence and functional
      data including sequence conservation, protein domains and interactions, and
      regulatory data. We found that these classifiers are able to distinguish between
      known cancer genes and other human genes. Furthermore, the classifiers also
      discriminate candidate cancer genes from a recent mutational screen from other
      human genes. We provide a web-based facility through which cancer biologists may
      access our results and we propose computational cancer gene classification as a
      useful method of prioritizing candidate cancer genes identified in oncogenomic
      studies.

PMID- 18710883
TI  - Advantages of q-PCR as a method of screening for gene targeting in mammalian
      cells using conventional and whole BAC-based constructs.
AB  - We evaluate here the use of real-time quantitative PCR (q-PCR) as a method for
      screening for homologous recombinants generated in mammalian cells from either
      conventional gene-targeting constructs or whole BAC-based constructs. Using gene
      targeted events at different loci, we show that q-PCR is a highly sensitive and
      accurate method for screening for conventional gene targeting that can reduce the
      number of clones requiring follow-up screening by Southern blotting. We further
      compared q-PCR to fluorescent in situ hybridization (FISH) for the detection of
      gene-targeting events using full-length BAC-based constructs designed to
      introduce mutations either into one gene or simultaneously into two adjacent
      genes. We find that although BAC-based constructs appeared to have high rates of
      homologous recombination when evaluated by FISH, screening by FISH was prone to
      false positives that were detected by q-PCR. Our results demonstrate the utility
      of q-PCR as a screening tool for gene targeting and further highlight potential
      problems with the use of whole BAC-based constructs for homologous recombination.

PMID- 18710884
TI  - Epidemiology of highly endemic multiply antibiotic-resistant shigellosis in
      children in the Peruvian Amazon.
AB  - OBJECTIVE: Our goal was to estimate the impact of a Shigella vaccine in an area
      where shigellosis is endemic by characterizing the disease burden and antibiotic
      resistance profiles of isolates and by determining the prevalence of Shigella
      flexneri serotypes. PATIENTS AND METHODS: We conducted a 43-month-long
      prospective, community-based diarrheal disease surveillance in 442 children <72
      months of age in the Peruvian Amazon between October 1, 2002, and April 15, 2006.
      RESULTS: The incidence of diarrheal disease was 4.38 episodes per child-year. The
      incidence rate for shigellosis was 0.34 episodes per child-year in children <72
      months of age and peaked in children between 12 and 23 months at 0.43 episodes
      per child-year. Maternal education at or beyond the primary grade level, piped
      water supply, weight-for-age z score, and improved water-storage practices were
      the most significant determinants of disease in this community with living
      conditions comparable to many rural areas in the developing world. CONCLUSIONS:
      Children living in this region had a 20-fold higher rate of disease incidence
      detected by active surveillance as those recently estimated by passive detection.
      Most symptomatic disease was caused by S flexneri, although the diversity of
      serotypes will require a multivalent vaccine to have a significant impact on the
      burden of disease caused by shigellosis. Several other public health disease
      control interventions targeted at water source and improved storage, nutritional
      interventions, and improved maternal education seem to have a greater impact than
      a univalent S flexneri 2a vaccine.

PMID- 18710885
TI  - Inflammatory gene polymorphisms and susceptibility to kawasaki disease and its
      arterial sequelae.
AB  - OBJECTIVE: We tested the hypothesis that single-nucleotide polymorphisms of
      inflammatory genes C-reactive protein (CRP) and tumor necrosis factor alpha (TNF
      alpha) may exert influence on susceptibility to Kawasaki disease and its arterial
      sequelae. METHODS: We analyzed the CRP +1444 C-->T and TNF-alpha -308 G-->A
      polymorphisms in 167 patients aged 8.9 +/- 4.1 years with a history of Kawasaki
      disease (73 with and 94 without coronary aneurysms) and 124 healthy control
      subjects. For patients with Kawasaki disease, we further determined whether these
      single-nucleotide polymorphisms were associated with coronary aneurysms, carotid
      arterial stiffening, and intima-media thickness. RESULTS: Genotypic and allelic
      frequencies of CRP +1444 for T carrier and TNF-alpha -308 for A carrier were
      significantly higher in patients than in control subjects. The genotypic and
      allelic distributions did not differ between patients with and those without
      coronary aneurysms; however, patients with CRP +1444 CT/TT genotype compared with
      those with a CC genotype and patients with TNF-alpha -308 GA/AA genotype compared
      with those with a GG genotype had significantly greater carotid arterial
      stiffness and intima-media thickness. Carriers of both CRP +1444 T allele and TNF
      alpha -308 A allele had the highest susceptibility to Kawasaki disease and a
      significant trend of increased arterial stiffness and intima-media thickness
      compared with those who carried either 1 or none of the rare alleles. Multiple
      linear regression analysis identified CRP +1444 allele carrier as a significant
      determinant of both carotid stiffness and carotid intima-media thickness and TNF
      alpha -308 A allele carrier as a determinant of only intima-media thickness.
      CONCLUSIONS: Our findings suggest that CRP +1444 C-->T and TNF-alpha -308 G-->A
      polymorphisms are associated with predisposition to Kawasaki disease and, in
      patients with Kawasaki disease, increased carotid arterial stiffness and intima
      media thickness in the long-term.

PMID- 18710886
TI  - The effect of heat waves on hospital admissions for renal disease in a temperate
      city of Australia.
AB  - BACKGROUND: A rarely investigated consequence of heat exposure is renal
      dysfunction resulting from dehydration and hyperthermia. Our study aims to
      quantify the relationship between exposure to extreme high temperatures and renal
      morbidity in South Australia. METHODS: Poisson regression accounting for over
      dispersion, seasonality and long-term trend was used to estimate the effect of
      heat waves on hospital admissions for renal disease, acute renal failure and
      renal dialysis over a 12-year period. Selected comorbidities were investigated as
      possible contributing risk factors. RESULTS: Admissions for renal disease and
      acute renal failure were increased during heat waves compared with non-heat wave
      periods with an incidence rate ratio of 1.100 [95% confidence intervals (CI)
      1.003-1.206] and 1.255 (95% CI 1.037-1.519), respectively. Hospitalizations for
      dialysis showed no corresponding increase. Comorbid diabetes did not increase the
      risk of renal admission, however 'effects of heat and light' and 'exposure to
      excessive natural heat' (collectively termed effects of heat) were identified as
      risk factors. CONCLUSION: Our findings suggest that as heat waves become more
      frequent, the burden of renal morbidity may increase in susceptible individuals
      as an indirect consequence of global warming.

PMID- 18710887
TI  - Analysis of 2 x 2 tables of frequencies: matching test to experimental design.
AB  - BACKGROUND: Biomedical investigators often use unsuitable statistical techniques
      for analysing the 2 x 2 tables that result from their experimental observations.
      This is because they are confused by the conflicting, and sometimes inaccurate,
      advice they receive from statistical texts or statistical consultants. METHODS:
      These consist of a review of published work, and the use of five different
      statistical procedures to analyse a 2 x 2 table, executed by StatXact 8.0,
      Testimate 6.0, Stata 10.0, SAS 9.1 and SPSS 16.0. Discussion and Conclusions It
      is essential to classify a 2 x 2 table before embarking on its analysis. A useful
      classification is into (i) Independence trials (doubly conditioned). These almost
      never occur in biomedical research because they involve predetermining the column
      and row totals in a 2 x 2 table. The Fisher exact test is the best method for
      analysing these trials. (ii) Comparative trials (singly conditioned). These
      correspond to the usual experimental design in biomedical work, in which a sample
      of convenience is randomized into two treatment groups, so that the group
      (column) totals are fixed in advance. The proper tests of significance are exact
      tests on the odds ratio, on the ratio of proportions (relative risk and risk
      ratio) or on the difference between proportions. (iii) Double dichotomy trials
      (unconditional). In these, a genuine random sample is taken from a defined
      population. Thus, neither column nor row totals are fixed in advance. The only
      practicable test is Pearson's chi(2)-test. In analysing any of the above trials,
      exact tests are to be much preferred to asymptotic (approximate) tests. The
      different commercial software packages use different algorithms for exact tests,
      and can give different outcomes in terms of P-values and confidence intervals.
      The most useful are StatXact and Testimate.

PMID- 18710888
TI  - Effects of demographic variables on mental illness admission for victims of
      interpersonal violence.
AB  - BACKGROUND: To assess the effects of demographic factors on mental illness
      admission for victims of interpersonal violence. METHODS: A population-based
      retrospective cohort study was conducted to investigate victims of violence using
      the 1990-2004 linked data extracted from the Western Australia Hospital Morbidity
      Data System and the Mental Health Information System. Factors associated with the
      risk for hospitalization for mental illness were assessed by logistic regression
      analysis. RESULTS: Among the 25,427 victims admitted to hospital for at least one
      episode of interpersonal violence during the study period, 6395 (25%) had been
      hospitalized with a mental illness diagnosis. Female [odds ratio (OR) 1.54, 95%
      CI 1.40-1.63] and Indigenous (OR 1.47, 95% CI 1.34-1.57) victims of violence were
      significantly more likely to be admitted for mental illness. The presence of
      additional co-morbidity also increased the risk (OR 1.49, 95% CI 1.44-1.54).
      Other variables that significantly increased the risk of mental illness admission
      were advancing age, other methods of assault and victims who had been separated,
      divorced or widowed. CONCLUSIONS: The results are beneficial for designing and
      implementing intervention strategies to reduce the adverse consequences of
      interpersonal violence particularly for women and Indigenous victims of violence.

PMID- 18710891
TI  - Introduction to a mini-forum on "glyconutrients".

PMID- 18710895
TI  - Evidence behind the WHO guidelines: Hospital care for children: what is the
      evidence of safety of gentamicin use in children?

PMID- 18710896
TI  - Significance of organic cation transporter 3 (SLC22A3) expression for the
      cytotoxic effect of oxaliplatin in colorectal cancer.
AB  - The effect of oxaliplatin against colorectal cancer is superior to that of
      cisplatin, but the molecular mechanism(s) involved is not clear. We found
      previously that oxaliplatin, but not cisplatin, was transported by human (h) and
      rat organic cation transporter 3 (OCT3)/SLC22A3. In the present study, we
      examined whether hOCT3 was significantly involved in the oxaliplatin-induced
      cytotoxicity and accumulation of platinum in colorectal cancer. The level of
      hOCT3 mRNA in the colon was 9.7-fold higher in cancerous than in normal tissues
      in six Japanese patients (P = 0.0247). In human colorectal cancer-derived cell
      lines, the mRNA of hOCT3 was highly expressed compared with that of other organic
      cation transporters. The release of lactate dehydrogenase (LDH) and accumulation
      of platinum with oxaliplatin treatment were increased in SW480 cells transfected
      with hOCT3 cDNA compared with empty vector-transfected cells. T84 and SW837
      cells, with high levels of hOCT3, released more LDH and accumulated more platinum
      after oxaliplatin treatment than low hOCT3-expressing cells such as SW480,
      HCT116, HT29, and Lovo. However, the amount of platinum accumulated after
      cisplatin treatment did not differ among these six cell lines. The levels of
      hOCT3 expression in colon and rectum were also higher in cancerous than in normal
      tissues in Caucasian patients as determined by dot blotting. In conclusion, the
      hOCT3-mediated uptake of oxaliplatin into the cancers was suggested to be
      important for its cytotoxicity, and hOCT3 expression may be a marker for cancer
      chemotherapy including oxaliplatin.

PMID- 18710897
TI  - Identification of stereoisomeric metabolites of meisoindigo in rat liver
      microsomes by achiral and chiral liquid chromatography/tandem mass spectrometry.
AB  - N-methylisoindigotin, abbreviated as meisoindigo, has been a routine therapeutic
      agent in the clinical treatment of chronic myelogenous leukemia in China since
      the 1980s. However, information relevant to in vitro metabolism of meisoindigo is
      limited. In this study, in vitro stereoisomeric metabolites of meisoindigo in rat
      liver microsomes were identified for the first time by achiral and chiral liquid
      chromatography/tandem mass spectrometry, together with proton NMR spectroscopy
      and synchrotron infrared spectroscopy. The major in vitro phase I metabolites of
      meisoindigo were tentatively identified as stereoselective-reduced meisoindigo,
      which comprised a pair of (3-R, 3'-R) and (3-S, 3'-S) enantiomers with lower
      abundance, as well as another pair of (3-R, 3'-S) and (3-S, 3'-R) enantiomers
      with higher abundance. One type of minor in vitro metabolites was tentatively
      identified as stereoselective N-demethyl-reduced meisoindigo including a pair of
      (3-R, 3'-R) and (3-S, 3'-S) enantiomers, as well as one meso compound. Another
      type of minor in vitro metabolites was tentatively identified as both
      stereoselective and regioselective monohydroxyl-reduced meisoindigo. Based on the
      metabolite profiling, three parallel metabolic pathways of meisoindigo in rat
      liver microsomes were proposed.

PMID- 18710898
TI  - Comment on: Infliximab, etanercept and adalimumab for the treatment of ankylosing
      spondylitis: cost-effectiveness evidence and NICE guidance.

PMID- 18710899
TI  - Acupuncture for rheumatoid arthritis: a systematic review.
AB  - The aim of this systematic review is to evaluate the available evidence, from
      randomized clinical trials (RCTs), of acupuncture for treating patients with RA.
      Systematic searches were conducted on 17 databases up to April 2008 without the
      language restriction. All RCTs of acupuncture, with or without electrical
      stimulation or moxibustion, for patients with RA were considered for inclusion. A
      total of 236 potentially relevant studies were identified and eight RCTs were
      included. Four RCTs compared the effects of manual or electro-acupuncture with
      penetrating or non-penetrating sham acupuncture and failed to show specific
      effects of acupuncture on pain [n = 88; weighted mean differences (WMD), 10 cm
      VAS -0.46; 95% CI -1.70, 0.77; P = 0.46; heterogeneity: tau(2) = 0.19; chi(2) =
      2.38; P = 0.30; I (2) = 16%] or other outcome measures. One RCT compared manual
      acupuncture with indomethacin and suggested favourable effects of acupuncture in
      terms of total response rate. Three RCTs tested acupuncture combined with
      moxibustion, vs conventional drugs and failed to show that acupuncture plus
      moxibustion was superior to conventional drugs in terms of response rate (n =
      345; RR 1.12; 95% CI 0.99, 1.28; P = 0.08; heterogeneity: tau(2) = 0.00; chi(2) =
      1.34; P = 0.51; I(2) = 0%), pain reduction (n = 105; WMD, 10 cm VAS 1.53; 95% CI 
      0.57, 3.63; P = 0.15; heterogeneity: tau(2) = 1.18; chi(2) = 1.81; P = 0.18; I(2)
      = 45%) or joint swelling index (n = 105; WMD, 10 cm VAS 0.25; 95% CI -1.31, 1.82;
      P = 0.75; heterogeneity: tau(2) = 0.18;chi(2) = 1.14; P = 0.28; I(2) = 13%). In
      conclusion, penetrating or non-penetrating sham-controlled RCTs failed to show
      specific effects of acupuncture for pain control in patients with RA. More
      rigorous research seems to be warranted.

PMID- 18710900
TI  - Discordant perspectives of rheumatologists and patients on COBRA combination
      therapy in rheumatoid arthritis.
AB  - OBJECTIVE: The COBRA therapy (combination therapy in early rheumatoid arthritis)
      has proven to be an effective treatment for early RA, but is rarely prescribed. A
      survey showed reluctance of Dutch reumatologists to apply COBRA therapy in early
      RA. The present qualitative study was carried out to further explore the
      reservation of Dutch rheumatologists towards prescribing COBRA therapy and
      include patients' view on (components of) COBRA therapy. METHODS: Two focus group
      discussions were undertaken for rheumatologists (n(1) = 8, n(2) = 7) and two for
      patients (n(1) = 4, n(2) = 8). In addition, in-depth interviews were conducted
      with 11 rheumatologists and 1 patient. These were taped and transcribed. Two
      independent researchers identified themes and these were discussed with three
      other researchers. RESULTS: Rheumatologists were positive concerning
      effectiveness of COBRA therapy, but highly concerned about their patients'
      possible negative reaction to the large amount of pills to be prescribed. In
      addition, rheumatologists perceived lack of time explaining and prescribing COBRA
      therapy and felt uncomfortable prescribing high doses of prednisolone. Patients
      were positive about an aggressive combination therapy such as COBRA, and they had
      no qualms taking many pills if this could improve their prognosis. Patients
      associated prednisolone with negative side-effects, but were also aware of the
      benefits and the need of prednisolone in rough times. A decrease in the amount of
      pills after intensive treatment was highly appreciated. CONCLUSION:
      Rheumatologists and patients differed in opinion about the use of COBRA therapy.
      Rheumatologists were particularly concerned about their patients' reaction
      towards them prescribing such an aggressive and complex therapy, whereas
      patients, while aware of the side-effects, were most interested in suppressing
      illness symptoms and reducing future damage regardless of the amount of pills.

PMID- 18710901
TI  - Gout and the risk of type 2 diabetes among men with a high cardiovascular risk
      profile.
AB  - OBJECTIVE: Our objective was to evaluate the independent relation between a
      history of gout and the future risk of type 2 diabetes among men with a high
      cardiovascular risk profile. METHODS: We prospectively examined over a 6-yr
      period the relation between gout and the risk of incident type 2 diabetes in 11
      351 male participants from the Multiple Risk Factor Intervention Trial (MRFIT).
      Incident diabetes was defined based on the American Diabetes Association (ADA)
      criteria for epidemiological studies. Cox proportional hazards regression was
      used to adjust for potential confounders. RESULTS: We documented 1215 new cases
      of type 2 diabetes. After adjusting for age, BMI, smoking, family history of type
      2 diabetes, alcohol intake, dietary factors and presence of individual components
      of the metabolic syndrome, the multivariate relative risk (RR) for incident type
      2 diabetes among men with gout at baseline, as compared with men without gout,
      was 1.34 (95% CI 1.09, 1.64). When we further adjusted for serum uric acid
      levels, the association remained significant (RR 1.26; 95% CI 1.02, 1.54). When
      we updated the status of gout annually during follow-up as a time-varying
      covariate, the association remained similar. The association also remained
      similar in our subgroup analyses by major covariates (P-values for interaction
      >0.16). CONCLUSIONS: These findings from men with a high cardiovascular risk
      profile suggest that men with gout are at a higher future risk of type 2 diabetes
      independent of other known risk factors. These data expand on well-established,
      cross-sectional associations between hyperuricaemia, gout and the metabolic
      syndrome, and extend the link to the future risk of type 2 diabetes.

PMID- 18710902
TI  - Gestational diabetes screening and glycaemic management; national survey on
      behalf of the Association of British Clinical Diabetologists.
AB  - BACKGROUND: There is no UK consensus for screening methodology, diagnosis and
      management of gestational diabetes mellitus (GDM). AIM: To evaluate routine
      practice for GDM management across the UK. METHODS: Questionnaires were sent to
      all members of the Association of British Clinical Diabetologists. They were
      asked to describe how patients were screened for GDM, the diagnostic criteria and
      subsequent management and clinical targets. Centres that did not respond were
      followed up by personal communication. Variability trends within regions were
      assessed. RESULTS: The response rate averaged 46% nationally (35-67%). Most (85%)
      units hold a joint clinic, regardless of the size. Most (82%) centres routinely
      screen for GDM; half universally and half screening high risk pregnancies only.
      Screening tests, cut-off values, timings and subsequent action vary widely. The
      first screening test to be used varies, with 40% using glycosuria, followed by
      random plasma glucose (RPG)(28%), high risk features (11%) then FPG in 6%. Cut
      off values for both random and plasma glucose as screening methods also vary. The
      75 g oral glucose tolerance test (OGTT) is the most likely confirmatory test to
      be used if initial screening is positive; however, clinicians rely on different
      cut-off values and timing. Most (95%) centres routinely assess foetal growth.
      Postpartum screening is undertaken by 90%, using a 75 g OGTT (93%). Most (90%)
      centres counsel patients about their high risk for further GDM and type 2
      diabetes mellitus. Variability trends in any of the responses could not be
      detected between different regions in the UK. CONCLUSION: Standards for GDM
      screening and management vary significantly across the UK. Although most centres
      utilize the 75 g OGTT to confirm the diagnosis, there is no consistency in its
      interpretation. This survey confirms the urgent need for consensus guideline
      development.

PMID- 18710903
TI  - Activin A reduces luteinisation of human luteinised granulosa cells and has
      opposing effects to human chorionic gonadotropin in vitro.
AB  - The transition of the dominant follicle into the corpus luteum is of fundamental
      reproductive importance. Luteinisation involves disparate changes in the gene
      expression of follicular granulosa cells that differentiate into the granulosa
      lutein cells of the corpus luteum after the gonadotrophin surge. We have shown
      that activin and human chorionic gonadotropin (hCG) have opposing effects during
      luteolysis. Therefore, we hypothesised that activin A was an inhibitor of
      luteinisation that was blocked during the pre-ovulatory gonadotrophin surge.
      Ovarian tissue and cells were collected from women with regular cycles having
      hysterectomy and women undergoing oocyte retrieval for assisted conception. Genes
      that changes during luteinisation were investigated in primary cultures of
      luteinised granulosa cells exposed to activin A and hCG in vitro. hCG promotes a
      luteinised granulosa cell phenotype, while activin A promotes a more follicular
      phenotype in luteinised cells by upregulating granulosa cells markers such as
      FSHR, HSD11B2 and downregulating LHCGR. In addition, activin A blocked hCG
      upregulation of STAR, HSD3B1 and HSD11B1 and downregulation of oestrogen receptor
      alpha. Activin A antagonised hCG effects in a dose-dependent manner and could
      block the hCG-stimulated molecular inhibitors of activin action (inhibin alpha
      subunit, follistatin and TGFBR3). These studies show that hCG and activin A have
      opposing effects on luteinised granulosa cells and some effects of activin are
      seen only in the presence of hCG. While hCG can inhibit activin action in
      granulosa cells to facilitate luteinisation, activin A can promote an
      unluteinised phenotype in luteinised granulosa cells. This confirms the
      importance of adequate activin withdrawal during luteinisation in women.

PMID- 18710905
TI  - Nocturnal non-invasive ventilation in addition to rehabilitation in hypercapnic
      patients with COPD.
AB  - BACKGROUND: Long-term non-invasive positive pressure ventilation (NIPPV) might
      improve the outcomes of pulmonary rehabilitation in patients with chronic
      obstructive pulmonary disease (COPD) with chronic respiratory failure. A study
      was undertaken to investigate whether nocturnal NIPPV in addition to pulmonary
      rehabilitation improves health-related quality of life, functional status and gas
      exchange compared with pulmonary rehabilitation alone in patients with COPD with
      chronic hypercapnic respiratory failure. METHODS: 72 patients with COPD were
      randomly assigned to nocturnal NIPPV in addition to rehabilitation (n = 37) or
      rehabilitation alone (n = 35). Outcome measures were assessed before and after
      the 3-month intervention period. RESULTS: The Chronic Respiratory Questionnaire
      total score improved 15.1 points with NIPPV + rehabilitation compared with 8.7
      points with rehabilitation alone. The difference of 7.5 points was not
      significant (p = 0.08). However, compared with rehabilitation alone, the
      difference in the fatigue domain was greater with NIPPV + rehabilitation (mean
      difference 3.3 points, p<0.01), as was the improvement in the Maugeri Respiratory
      Failure questionnaire total score (mean difference -10%, p<0.03) and its
      cognition domain (mean difference -22%, p<0.01). Furthermore, the addition of
      NIPPV improved daytime arterial carbon dioxide pressure (mean difference -0.3
      kPa; p<0.01) and daily step count (mean difference 1269 steps/day, p<0.01). This
      was accompanied by an increased daytime minute ventilation (mean difference 1.4
      l; p<0.001). CONCLUSION: Non-invasive ventilation augments the benefits of
      pulmonary rehabilitation in patients with COPD with chronic hypercapnic
      respiratory failure as it improves several measures of health-related quality of
      life, functional status and gas exchange.

PMID- 18710906
TI  - Healthy but not RSV-infected lung epithelial cells profoundly inhibit T cell
      activation.
AB  - BACKGROUND: Respiratory viruses, including respiratory syncytial virus (RSV), can
      cause asthma exacerbations and bronchiolitis. Both conditions are associated with
      enhanced cognate immune responses and inflammation and reduced immune regulation.
      Lung epithelial cells (LECs) can contribute to antiviral and allergic immune
      responses while gut epithelial cells can inhibit effector T cell responses. A
      study was performed to determine whether healthy LECs regulate antigen-specific T
      cell responses and if this regulation is lost during RSV infection. METHODS: LA4
      cells, a murine LEC line, infected with RSV or primary murine LECs were co
      cultured with ovalbumin-specific T cell receptor transgenic CD4+ T cells from
      DO11.10 mice and ovalbumin-pulsed bone marrow-derived dendritic cells (DC) to
      assess T cell proliferation by flow cytometry and cytokine production. RESULTS:
      The presence of LECs abrogated DC-induced T cell proliferation and significantly
      reduced T cell cytokine release. These effects of LECs were predominantly contact
      dependent, primarily affected T cells directly and were partly mediated by
      transforming growth factor beta. Soluble factors and DC-mediated effects also
      contributed to T cell inhibition. RSV infection of LECs reduced their inhibitory
      capacity in an infection dose-dependent manner. This was independent of
      proinflammatory cytokines released by infected LECs, but in part due to Toll-like
      receptor activation and to infection-induced cell death. CONCLUSION: Healthy LECs
      are potent inhibitors of T cell activation, but this regulatory function is lost
      after RSV infection. These findings suggest a central role for LECs in
      maintaining the tolerogenic environment of healthy lungs. Loss of this regulatory
      capacity after viral infection may allow development of excessive cognate immune
      responses and pulmonary inflammation.

PMID- 18710907
TI  - Synthesis, antimalarial activity, and intracellular targets of MEFAS, a new
      hybrid compound derived from mefloquine and artesunate.
AB  - A new synthetic antimalarial drug, a salt derived from two antimalarial
      molecules, mefloquine (MQ) and artesunate (AS), here named MEFAS, has been tested
      for its pharmacological activity. Combinations of AS plus MQ hydrochloride are
      currently being used in areas with drug-resistant Plasmodium falciparum
      parasites; although AS clears parasitemia in shorter time periods than any other
      antimalarial drug, it does not cure infected patients; in addition, MQ causes
      side effects and is rather expensive, important problems considering that malaria
      affects mostly populations in poor countries. Here, we show that MEFAS is more
      effective than the combination of AS and MQ, tested in parallel at different mass
      proportions, against P. falciparum (chloroquine-resistant clone W2 and
      chloroquine-sensitive clone 3D7) in vitro and in mice infected with Plasmodium
      berghei, promoting cure of this infection. MEFAS tested against HepG2 hepatoma
      cells exhibited lower toxicity than the antimalarials AS and MQ alone or
      combined. Possible targets of MEFAS have been studied by confocal microscopy
      using fluorescent probes (Fluo-4 AM and BCECF-AM) in P. falciparum synchronous
      culture of W2-infected red blood cells. Dynamic images show that MEFAS exhibited
      intracellular action increasing cytoplasmic Ca(2+) at 1.0 ng/ml. This effect was
      also observed in the presence of tapsigargin, an inhibitor of SERCA, suggesting
      an intracellular target distinct from the endoplasmic reticulum. Trophozoites
      loaded with BCECF-AM, when treated with MEFAS, were still able to mobilize
      protons from the digestive vacuole (DV), altering the pH gradient. However, in
      the presence of bafilomycin A1, an inhibitor of the H(+) pump from acidic
      compartments of eukaryotic cells, MEFAS had no action on the DV. In conclusion,
      the endoplasmic reticulum and DV are intracellular targets for MEFAS in
      Plasmodium sp., suggesting two modes of action of this new salt. Our data support
      MEFAS as a candidate for treating human malaria.

PMID- 18710908
TI  - Effects of exposure of Clostridium difficile PCR ribotypes 027 and 001 to
      fluoroquinolones in a human gut model.
AB  - The incidence of Clostridium difficile infection is increasing, with reports
      implicating fluoroquinolone use. A three-stage chemostat gut model was used to
      study the effects of three fluoroquinolones (ciprofloxacin, levofloxacin, and
      moxifloxacin) on the gut microbiota and two epidemic C. difficile strains,
      strains of PCR ribotypes 027 and 001, in separate experiments. C. difficile total
      viable counts, spore counts, and cytotoxin titers were determined. The emergence
      of C. difficile isolates with reduced antibiotic susceptibility was monitored
      with fluoroquinolone-containing medium, and molecular analysis of the quinolone
      resistance-determining region was performed. C. difficile spores were quiescent
      in the absence of fluoroquinolones. Instillation of each fluoroquinolone led to
      C. difficile spore germination and high-level cytotoxin production. High-level
      toxin production occurred after detectable spore germination in all experiments
      except those with C. difficile PCR ribotype 027 and moxifloxacin, in which marked
      cytotoxin production preceded detectable germination, which coincided with
      isolate recovery on fluoroquinolone-containing medium. Three C. difficile PCR
      ribotype 027 isolates and one C. difficile PCR ribotype 001 isolate from
      fluoroquinolone-containing medium exhibited elevated MICs (80 to > or =180
      mg/liter) and possessed mutations in gyrA or gyrB. These in vitro results suggest
      that all fluoroquinolones have the propensity to induce C. difficile infection,
      regardless of their antianaerobe activities. Resistant mutants were seen only
      following moxifloxacin exposure.

PMID- 18710909
TI  - Improved antimicrobial activity of linezolid against vancomycin-intermediate
      Staphylococcus aureus.

PMID- 18710910
TI  - Aspergillus fumigatus forms biofilms with reduced antifungal drug susceptibility
      on bronchial epithelial cells.
AB  - Aspergillus fumigatus is a leading cause of death in immunocompromised patients
      and a frequent colonizer of the respiratory tracts of asthma and cystic fibrosis
      (CF) patients. Biofilms enable bacteria and yeasts to persist in infections and
      can contribute to antimicrobial resistance. We investigated the ability of A.
      fumigatus to form biofilms on polystyrene (PS) and human bronchial epithelial
      (HBE) and CF bronchial epithelial (CFBE) cells. We developed a novel in vitro
      coculture model of A. fumigatus biofilm formation on HBE and CFBE cells. Biofilm
      formation was documented by dry weight, scanning electron microscopy (SEM), and
      confocal scanning laser microscopy (CSLM). The in vitro antifungal activities of
      seven antifungal drugs were tested by comparing planktonic and sessile A.
      fumigatus strains. A. fumigatus formed an extracellular matrix on PS and HBE and
      CFBE cells as evidenced by increased dry weight, SEM, and CSLM. These biofilms
      exhibited decreased antifungal drug susceptibility and were adherent to the
      epithelial cells, with fungi remaining viable throughout 3 days. These
      observations might have implications for treatment of A. fumigatus colonization
      in chronic lung diseases and for its potential impact on airway inflammation,
      damage, and infection.

PMID- 18710911
TI  - Genomewide expression profiling of cryptolepine-induced toxicity in Saccharomyces
      cerevisiae.
AB  - We have used the budding yeast Saccharomyces cerevisiae to identify genes that
      may confer sensitivity in vivo to the antimalarial and cytotoxic agent
      cryptolepine. Five S. cerevisiae strains, with different genetic backgrounds in
      cell permeability and DNA damage repair mechanisms, were exposed to several
      concentrations of cryptolepine. Cryptolepine showed a relatively mild toxicity
      for wild-type strains, which was augmented by either increasing cell permeability
      (Deltaerg6 or ISE2 strains) or disrupting DNA damage repair (Deltarad52 strains).
      These results are compatible with the ability of cryptolepine to intercalate into
      DNA and thus promote DNA lesions. The effects of low concentrations of
      cryptolepine (20% and 40% inhibitory concentrations [IC(20) and IC(40)]) were
      analyzed by comparing the gene expression profiles of treated and untreated
      Deltaerg6 yeast cells. Significant changes in expression levels were observed for
      349 genes (117 upregulated and 232 downregulated). General stress-related genes
      constituted the only recognizable functional cluster whose expression was
      increased upon cryptolepine treatment, making up about 20% of upregulated genes.
      In contrast, analysis of the characteristics of downregulated genes revealed a
      specific effect of cryptolepine on genes related to iron transport or acid
      phosphatases, as well as a significant proportion of genes related to cell wall
      components. The effects of cryptolepine on the transcription of iron transport
      related genes were consistent with a loss of function of the iron sensor Aft1p,
      indicating a possible disruption of iron metabolism in S. cerevisiae. Since the
      interference of cryptolepine with iron metabolism is considered one of its
      putative antimalarial targets, this finding supports the utility of S. cerevisiae
      in drug-developing schemes.

PMID- 18710912
TI  - Vibrio cholerae O139 multiple-drug resistance mediated by Yersinia pestis pIP1202
      like conjugative plasmids.
AB  - A conjugative plasmid, pMRV150, which mediated multiple-drug resistance (MDR) to
      at least six antibiotics, including ampicillin, streptomycin, gentamicin,
      tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole, was identified
      in a Vibrio cholerae O139 isolate from Hangzhou, eastern China, in 2004.
      According to partial pMRV150 DNA sequences covering 15 backbone regions, the
      plasmid is most similar to pIP1202, an IncA/C plasmid in an MDR Yersinia pestis
      isolate from a Madagascar bubonic plague patient, at an identity of 99.99%
      (22,180/22,183 nucleotides). pMRV150-like plasmids were found in only 7.69%
      (1/13) of the O139 isolates tested during the early period of the O139 epidemic
      in Hangzhou (1994, 1996, and 1997); then the frequency increased gradually from
      60.00% (3/5) during 1998 and 1999 to 92.16% (47/51) during 2000 to 2006. Most
      (42/51) of the O139 isolates bearing pMRV150-like plasmids were resistant to five
      to six antibiotics, whereas the plasmid-negative isolates were resistant only to
      one to three antibiotics. In 12 plasmid-bearing O139 isolates tested, the pMRV150
      like plasmids ranged from approximately 140 kb to 170 kb and remained at
      approximately 1 or 2 copies per cell. High (4.50 x 10(-2) and 3.08 x 10(-2)) and
      low (0.88 x 10(-8) to 3.29 x 10(-5)) plasmid transfer frequencies, as well as no
      plasmid transfer (under the detection limit), from these O139 isolates to the
      Escherichia coli recipient were observed. The emergence of pMRV150-like or
      pIP1202-like plasmids in many bacterial pathogens and nonpathogens occupying
      diverse niches with global geographical distribution indicates an increasing risk
      to public health worldwide. Careful tracking of these plasmids in the microbial
      ecosystem is warranted.

PMID- 18710913
TI  - Human lactoferrin induces apoptosis-like cell death in Candida albicans: critical
      role of K+-channel-mediated K+ efflux.
AB  - Human lactoferrin (hLf) induced an apoptosis-like phenotype in Candida albicans
      cells, which includes phosphatidylserine externalization, nuclear chromatin
      condensation, DNA degradation, and increased reactive oxygen species (ROS)
      production. Intracellular ROS accumulation was seen to correlate with
      candidacidal activity in hLf-treated cells. Mitochondrial activity was involved
      as indicated by mitochondrial depolarization and increased hLf resistance of
      cells preincubated with sordarin or erythromycin, the latter of which inhibits
      protein synthesis in mitoribosomes. Interestingly, Cl(-)- and K(+)-channel
      blockers prevented the hLf antimicrobial activity, but only when cells were
      pretreated with the blocking agent (tetraethylammonium) prior to the hLf-induced
      K(+)-release period. These results indicate for the first time that K(+)-channel
      mediated K(+) efflux is required for the progression of apoptosis-like process in
      yeast, suggesting that this essential apoptotic event of higher eukaryotes has
      been evolutionary conserved among species ranging from yeasts to humans.

PMID- 18710914
TI  - ABC transporter Cdr1p contributes more than Cdr2p does to fluconazole efflux in
      fluconazole-resistant Candida albicans clinical isolates.
AB  - Fluconazole (FLC) remains the antifungal drug of choice for non-life-threatening
      Candida infections, but drug-resistant strains have been isolated during long
      term therapy with azoles. Drug efflux, mediated by plasma membrane transporters,
      is a major resistance mechanism, and clinically significant resistance in Candida
      albicans is accompanied by increased transcription of the genes CDR1 and CDR2,
      encoding plasma membrane ABC-type transporters Cdr1p and Cdr2p. The relative
      importance of each transporter protein for efflux-mediated resistance in C.
      albicans, however, is unknown; neither the relative amounts of each polypeptide
      in resistant isolates nor their contributions to efflux function have been
      determined. We have exploited the pump-specific properties of two antibody
      preparations, and specific pump inhibitors, to determine the relative expression
      and functions of Cdr1p and Cdr2p in 18 clinical C. albicans isolates. The
      antibodies and inhibitors were standardized using recombinant Saccharomyces
      cerevisiae strains that hyper-express either protein in a host strain with a
      reduced endogenous pump background. In all 18 C. albicans strains, including 13
      strains with reduced FLC susceptibilities, Cdr1p was present in greater amounts
      (2- to 20-fold) than Cdr2p. Compounds that inhibited Cdr1p-mediated function, but
      had no effect on Cdr2p efflux activity, significantly decreased the resistance to
      FLC of seven representative C. albicans isolates, whereas three other compounds
      that inhibited both pumps did not cause increased chemosensitization of these
      strains to FLC. We conclude that Cdr1p expression makes a greater functional
      contribution than does Cdr2p to FLC resistance in C. albicans.

PMID- 18710915
TI  - Virologic response to lopinavir-ritonavir-based antiretroviral regimens in a
      multicenter international clinical cohort: comparison of genotypic interpretation
      scores.
AB  - Several genotypic interpretation scores have been proposed for the evaluation of
      susceptibility to lopinavir/ritonavir (LPV/r) but have not been compared using an
      independent data set. This study was a retrospective multicenter cohort of
      patients initiating LPV/r-based therapy. The virologic response (VR) was defined
      as a viral load of <500 copies/ml at week 24. The genotypic interpretation scores
      surveyed were the LPV mutation score, the ViroLogic score, the ATU score, the
      Stanford database score, and the International AIDS Society-USA mutation list. Of
      the 103 patients included in the analysis, 76% achieved VR at 24 weeks. For
      scores with clinical breakpoints defined (LPV mutation, ATU, ViroLogic, and
      Stanford), over 80% of the patients below the breakpoints achieved VR, while 50%
      or less above the breakpoints responded. Protease mutations at positions 10, 54,
      and 82 and at positions 54, 84, and 90 were associated with a lack of VR in the
      univariate and multivariate analyses, respectively. The area under the receiver
      operator characteristic curves for the five genotypic interpretation scores
      studied ranged from 0.73 to 0.76. The study confirms that the currently available
      genotypic interpretation scores which are widely used by clinicians performed
      similarly well and can be effectively used to predict the virologic activity of
      LPV/r in treatment-experienced patients.

PMID- 18710916
TI  - Potential for hepatitis C virus resistance to nitazoxanide or tizoxanide.
AB  - Nitazoxanide and its primary metabolite, tizoxanide, inhibit hepatitis C virus
      (HCV) replication in HCV replicon systems. To study the potential for resistance,
      we subjected Huh7 cells harboring HCV replicons to serial passage in 250 muM G418
      and increasing concentrations of nitazoxanide or tizoxanide. Passage of the
      replicon-containing cell lines in either compound resulted in increases in the
      50% effective concentrations (EC(50)s) (7- to 13-fold), EC(90)s (14- to 36-fold),
      and 50% cytotoxic concentrations (2- to 4-fold) of both compounds. Serial passage
      in either compound did not alter the susceptibility of HCV replicons to ribavirin
      or 2'-C-methylcytidine. Interestingly, serial passage in nitazoxanide or
      tizoxanide resulted in increased sensitivity to alpha interferon 2b: EC(50)s and
      EC(90)s were reduced three- and eightfold, respectively. Replicons isolated from
      these cell lines had no greater ability to confer tizoxanide resistance, or
      increased susceptibility to alpha interferon, than replicons isolated from the
      parental cell line that had not previously been exposed to nitazoxanide or
      tizoxanide. These findings are indicative of a cell-mediated activity differing
      from that of other anti-HCV drugs but complementary with interferon and are
      consistent with the enhanced response rates observed clinically when nitazoxanide
      is combined with pegylated interferon therapy. Finally, unlike data for other
      compounds in advanced clinical development for HCV, these data are consistent
      with resistance in HCV replicon-containing cell lines conferred by changes in the
      host and not by mutations in the virus.

PMID- 18710917
TI  - In vitro antibacterial activity of vertilmicin and its susceptibility to
      modifications by the recombinant AAC6'-APH2'' enzyme.
AB  - Vertilmicin is a new semisynthetic aminoglycoside with a structure similar to
      that of netilmicin except for a methyl group at the C-6' position. In the present
      study, the in vitro antibacterial activity of vertilmicin was studied, and its
      susceptibility to modifications by the recombinant aminoglycoside bifunctional
      modifying enzyme AAC(6')-APH(2'') was compared with those of verdamicin and
      netilmicin. A total of 1,185 clinical isolates collected from hospitals in
      Beijing between 2000 and 2001 were subjected to the in vitro antibacterial
      activity evaluations, including MIC, minimum bactericidal concentration (MBC),
      and time-kill curve tests. The MICs were evaluated in non-gentamicin-resistant
      (gentamicin-susceptible and gentamicin-intermediate) strains and gentamicin
      resistant strains, respectively. For most of the non-gentamicin-resistant
      bacteria (except for the isolates of Pseudomonas spp.), the MIC(90)s of
      vertilmicin were in the range of 0.5 to 8 microg/ml, comparable to those of the
      reference aminoglycosides. For the gentamicin-resistant isolates, the three
      semisynthetic aminoglycosides (vertilmicin, netilmicin, and amikacin)
      demonstrated low MIC(50)s and/or MIC(90)s, as well as high percent susceptibility
      values. Among the study drugs, vertilmicin showed the lowest MIC(90)s, 16
      microg/ml, for the gram-positive gentamicin-resistant isolates of Staphylococcus
      aureus and Staphylococcus epidermidis. Meanwhile, vertilmicin was a potent
      bactericidal agent, with MBC/MIC ratios in the range of 1 to 2 for Escherichia
      coli, Klebsiella pneumoniae, and S. aureus and 1 to 4 for S. epidermidis. The
      time-kill curve determination further demonstrated that this effect was rapid and
      concentration dependent. In evaluations of susceptibility to modifications by the
      recombinant AAC(6')-APH(2'') with maximum rate of metabolism/K(m) measurements,
      vertilmicin exhibited susceptibilities to both acetylation and phosphorylation
      lower than those of netilmicin and verdamicin.

PMID- 18710918
TI  - Phenotypic characterization of two Ancylostoma caninum isolates with different
      susceptibilities to the anthelmintic pyrantel.
AB  - The anthelmintic pyrantel plays an important role in the control of
      gastrointestinal helminths of humans and domestic animals. Despite the
      demonstration of pyrantel resistance in several helminth species over the last 20
      years, the resistance mechanism remains unclear. It has been hypothesized that
      resistance may arise as a consequence of changes to the relative proportions of
      subpopulations of nicotinic acetylcholine receptors (nAchRs). To test this
      hypothesis, we examined the responses of two isolates of the canine hookworm
      Ancylostoma caninum with low-level resistance (isolate NT) and high-level
      resistance (isolate PR) to pyrantel to nicotinic agonist drugs reported to be
      selective for three nAchR subtypes. We used larval motility and conformation
      assays and force transduction experiments with adult worms. Pyrantel and
      levamisole were less potent against larvae of isolate PR than larvae of isolate
      NT (up to an 18-fold increase in the 50% inhibitory concentration); on the other
      hand, bephenium was more potent against larvae of isolate PR than larvae of
      isolate NT (twofold) and nicotine had the same potency against larvae of both
      isolates. In adults, pyrantel, levamisole, and nicotine were less potent against
      isolate PR than isolate NT (two- to threefold), but the potency of bephenium
      against the two isolates was equivalent. Our data indicate a complex pattern of
      nAchRs in this species and suggest that the two isolates differ in their relative
      sensitivities to agonists targeting different nAchRs.

PMID- 18710919
TI  - Voluntary muscle strength and endurance: 'The mechanism of voluntary muscle
      fatigue' by Charles Reid.

PMID- 18710920
TI  - E2-25K/Hip-2 regulates caspase-12 in ER stress-mediated Abeta neurotoxicity.
AB  - Amyloid-beta (Abeta) neurotoxicity is believed to contribute to the pathogenesis
      of Alzheimer's disease (AD). Previously we found that E2-25K/Hip-2, an E2
      ubiquitin-conjugating enzyme, mediates Abeta neurotoxicity. Here, we report that
      E2-25K/Hip-2 modulates caspase-12 activity via the ubiquitin/proteasome system.
      Levels of endoplasmic reticulum (ER)-resident caspase-12 are strongly up
      regulated in the brains of AD model mice, where the enzyme colocalizes with E2
      25K/Hip-2. Abeta increases expression of E2-25K/Hip-2, which then stabilizes
      caspase-12 protein by inhibiting proteasome activity. This increase in E2-25K/Hip
      2 also induces proteolytic activation of caspase-12 through its ability to induce
      calpainlike activity. Knockdown of E2-25K/Hip-2 expression suppresses neuronal
      cell death triggered by ER stress, and thus caspase-12 is required for the E2
      25K/Hip-2-mediated cell death. Finally, we find that E2-25K/Hip-2-deficient
      cortical neurons are resistant to Abeta toxicity and to the induction of ER
      stress and caspase-12 expression by Abeta. E2-25K/Hip-2 is thus an essential
      upstream regulator of the expression and activation of caspase-12 in ER stress
      mediated Abeta neurotoxicity.

PMID- 18710921
TI  - Mechanotransduction in an extracted cell model: Fyn drives stretch- and flow
      elicited PECAM-1 phosphorylation.
AB  - Mechanosensing followed by mechanoresponses by cells is well established, but the
      mechanisms by which mechanical force is converted into biochemical events are
      poorly understood. Vascular endothelial cells (ECs) exhibit flow- and stretch
      dependent responses and are widely used as a model for studying
      mechanotransduction in mammalian cells. Platelet EC adhesion molecule 1 (PECAM-1)
      is tyrosine phosphorylated when ECs are exposed to flow or when PECAM-1 is
      directly pulled, suggesting that it is a mechanochemical converter. We show that
      PECAM-1 phosphorylation occurs when detergent-extracted EC monolayers are
      stretched, indicating that this phosphorylation is mechanically triggered and
      does not require the intact plasma membrane and soluble cytoplasmic components.
      Using kinase inhibitors and small interfering RNAs, we identify Fyn as the PECAM
      1 kinase associated with the model. We further show that stretch- and flow
      induced PECAM-1 phosphorylation in intact ECs is abolished when Fyn expression is
      down-regulated. We suggest that PECAM-1 and Fyn are essential components of a
      PECAM-1-based mechanosensory complex in ECs.

PMID- 18710922
TI  - Regional variation of microtubule flux reveals microtubule organization in the
      metaphase meiotic spindle.
AB  - Continuous poleward movement of tubulin is a hallmark of metaphase spindle
      dynamics in higher eukaryotic cells and is essential for stable spindle
      architecture and reliable chromosome segregation. We use quantitative fluorescent
      speckle microscopy to map with high resolution the spatial organization of
      microtubule flux in Xenopus laevis egg extract meiotic spindles. We find that the
      flux velocity decreases near spindle poles by approximately 20%. The regional
      variation is independent of functional kinetochores and centrosomes and is
      suppressed by inhibition of dynein/dynactin, kinesin-5, or both. Statistical
      analysis reveals that tubulin flows in two distinct velocity modes. We propose an
      association of these modes with two architecturally distinct yet spatially
      overlapping and dynamically cross-linked arrays of microtubules: focused polar
      microtubule arrays of a uniform polarity and slower flux velocities are
      interconnected by a dense barrel-like microtubule array of antiparallel
      polarities and faster flux velocities.

PMID- 18710923
TI  - Poleward transport of Eg5 by dynein-dynactin in Xenopus laevis egg extract
      spindles.
AB  - Molecular motors are required for spindle assembly and maintenance during cell
      division. How motors move and interact inside spindles is unknown. Using
      photoactivation and photobleaching, we measure mitotic motor movement inside a
      dynamic spindle. We find that dynein-dynactin transports the essential motor Eg5
      toward the spindle poles in Xenopus laevis egg extract spindles, revealing a
      direct interplay between two motors of opposite directionality. This transport
      occurs throughout the spindle except at the very spindle center and at the
      spindle poles, where Eg5 remains stationary. The variation of Eg5 dynamics with
      its position in the spindle is indicative of position-dependent functions of this
      motor protein. Our results suggest that Eg5 drives microtubule flux by
      antiparallel microtubule sliding in the spindle center, whereas the dynein
      dependent concentration of Eg5 outside the spindle center could contribute to
      parallel microtubule cross-linking. These results emphasize the importance of
      spatially differentiated functions of motor proteins and contribute to our
      understanding of spindle organization.

PMID- 18710924
TI  - Novel role of the muskelin-RanBP9 complex as a nucleocytoplasmic mediator of cell
      morphology regulation.
AB  - The evolutionarily conserved kelch-repeat protein muskelin was identified as an
      intracellular mediator of cell spreading. We discovered that its morphological
      activity is controlled by association with RanBP9/RanBPM, a protein involved in
      transmembrane signaling and a conserved intracellular protein complex. By
      subcellular fractionation, endogenous muskelin is present in both the nucleus and
      the cytosol. Muskelin subcellular localization is coregulated by its C terminus,
      which provides a cytoplasmic restraint and also controls the interaction of
      muskelin with RanBP9, and its atypical lissencephaly-1 homology motif, which has
      a nuclear localization activity which is regulated by the status of the C
      terminus. Transient or stable short interfering RNA-based knockdown of muskelin
      resulted in protrusive cell morphologies with enlarged cell perimeters.
      Morphology was specifically restored by complementary DNAs encoding forms of
      muskelin with full activity of the C terminus for cytoplasmic localization and
      RanBP9 binding. Knockdown of RanBP9 resulted in equivalent morphological
      alterations. These novel findings identify a role for muskelin-RanBP9 complex in
      pathways that integrate cell morphology regulation and nucleocytoplasmic
      communication.

PMID- 18710925
TI  - Structural basis for distinctive recognition of fibrinogen gammaC peptide by the
      platelet integrin alphaIIbbeta3.
AB  - Hemostasis and thrombosis (blood clotting) involve fibrinogen binding to integrin
      alpha(IIb)beta(3) on platelets, resulting in platelet aggregation.
      alpha(v)beta(3) binds fibrinogen via an Arg-Asp-Gly (RGD) motif in fibrinogen's
      alpha subunit. alpha(IIb)beta(3) also binds to fibrinogen; however, it does so
      via an unstructured RGD-lacking C-terminal region of the gamma subunit (gammaC
      peptide). These distinct modes of fibrinogen binding enable alpha(IIb)beta(3) and
      alpha(v)beta(3) to function cooperatively in hemostasis. In this study, crystal
      structures reveal the integrin alpha(IIb)beta(3)-gammaC peptide interface, and,
      for comparison, integrin alpha(IIb)beta(3) bound to a lamprey gammaC primordial
      RGD motif. Compared with RGD, the GAKQAGDV motif in gammaC adopts a different
      backbone configuration and binds over a more extended region. The integrin metal
      ion-dependent adhesion site (MIDAS) Mg(2+) ion binds the gammaC Asp side chain.
      The adjacent to MIDAS (ADMIDAS) Ca(2+) ion binds the gammaC C terminus, revealing
      a contribution for ADMIDAS in ligand binding. Structural data from this natively
      disordered gammaC peptide enhances our understanding of the involvement of gammaC
      peptide and integrin alpha(IIb)beta(3) in hemostasis and thrombosis.

PMID- 18710926
TI  - Single-molecule analysis of CD9 dynamics and partitioning reveals multiple modes
      of interaction in the tetraspanin web.
AB  - Tetraspanins regulate cell migration, sperm-egg fusion, and viral infection.
      Through interactions with one another and other cell surface proteins,
      tetraspanins form a network of molecular interactions called the tetraspanin web.
      In this study, we use single-molecule fluorescence microscopy to dissect dynamics
      and partitioning of the tetraspanin CD9. We show that lateral mobility of CD9 in
      the plasma membrane is regulated by at least two modes of interaction that each
      exhibit specific dynamics. The majority of CD9 molecules display Brownian
      behavior but can be transiently confined to an interaction platform that is in
      permanent exchange with the rest of the membrane. These platforms, which are
      enriched in CD9 and its binding partners, are constant in shape and localization.
      Two CD9 molecules undergoing Brownian trajectories can also codiffuse, revealing
      extra platform interactions. CD9 mobility and partitioning are both dependent on
      its palmitoylation and plasma membrane cholesterol. Our data show the high
      dynamic of interactions in the tetraspanin web and further indicate that the
      tetraspanin web is distinct from raft microdomains.

PMID- 18710927
TI  - Microtubules do not promote mitotic slippage when the spindle assembly checkpoint
      cannot be satisfied.
AB  - When the spindle assembly checkpoint (SAC) cannot be satisfied, cells exit
      mitosis via mitotic slippage. In microtubule (MT) poisons, slippage requires
      cyclin B proteolysis, and it appears to be accelerated in drug concentrations
      that allow some MT assembly. To determine if MTs accelerate slippage, we followed
      mitosis in human RPE-1 cells exposed to various spindle poisons. At 37 degrees C,
      the duration of mitosis in nocodazole, colcemid, or vinblastine concentrations
      that inhibit MT assembly varied from 20 to 30 h, revealing that different MT
      poisons differentially depress the cyclin B destruction rate during slippage. The
      duration of mitosis in Eg5 inhibitors, which induce monopolar spindles without
      disrupting MT dynamics, was the same as in cells lacking MTs. Thus, in the
      presence of numerous unattached kinetochores, MTs do not accelerate slippage.
      Finally, compared with cells lacking MTs, exit from mitosis is accelerated over a
      range of spindle poison concentrations that allow MT assembly because the SAC
      becomes satisfied on abnormal spindles and not because slippage is accelerated.

PMID- 18710928
TI  - Stress induces the assembly of RNA granules in the chloroplast of Chlamydomonas
      reinhardtii.
AB  - Eukaryotic cells under stress repress translation and localize these messenger
      RNAs (mRNAs) to cytoplasmic RNA granules. We show that specific stress stimuli
      induce the assembly of RNA granules in an organelle with bacterial ancestry, the
      chloroplast of Chlamydomonas reinhardtii. These chloroplast stress granules
      (cpSGs) form during oxidative stress and disassemble during recovery from stress.
      Like mammalian stress granules, cpSGs contain poly(A)-binding protein and the
      small, but not the large, ribosomal subunit. In addition, mRNAs are in continuous
      flux between polysomes and cpSGs during stress. Localization of cpSGs within the
      pyrenoid reveals that this chloroplast compartment functions in this stress
      response. The large subunit of ribulosebisphosphate carboxylase/oxygenase also
      assembles into cpSGs and is known to bind mRNAs during oxidative stress, raising
      the possibility that it plays a role in cpSG assembly. This discovery within such
      an organelle suggests that mRNA localization to granules during stress is a more
      general phenomenon than currently realized.

PMID- 18710929
TI  - The transcription factor NFATc2 controls IL-6-dependent T cell activation in
      experimental colitis.
AB  - The nuclear factor of activated T cells (NFAT) family of transcription factors
      controls calcium signaling in T lymphocytes. In this study, we have identified a
      crucial regulatory role of the transcription factor NFATc2 in T cell-dependent
      experimental colitis. Similar to ulcerative colitis in humans, the expression of
      NFATc2 was up-regulated in oxazolone-induced chronic intestinal inflammation.
      Furthermore, NFATc2 deficiency suppressed colitis induced by oxazolone
      administration. This finding was associated with enhanced T cell apoptosis in the
      lamina propria and strikingly reduced production of IL-6, -13, and -17 by mucosal
      T lymphocytes. Further studies using knockout mice showed that IL-6, rather than
      IL-23 and -17, are essential for oxazolone colitis induction. Administration of
      hyper-IL-6 blocked the protective effects of NFATc2 deficiency in experimental
      colitis, suggesting that IL-6 signal transduction plays a major pathogenic role
      in vivo. Finally, adoptive transfer of IL-6 and wild-type T cells demonstrated
      that oxazolone colitis is critically dependent on IL-6 production by T cells.
      Collectively, these results define a unique regulatory role for NFATc2 in colitis
      by controlling mucosal T cell activation in an IL-6-dependent manner. NFATc2 in T
      cells thus emerges as a potentially new therapeutic target for inflammatory bowel
      diseases.

PMID- 18710930
TI  - Citrullination of CXCL8 by peptidylarginine deiminase alters receptor usage,
      prevents proteolysis, and dampens tissue inflammation.
AB  - Biological functions of proteins are influenced by posttranslational
      modifications such as on/off switching by phosphorylation and modulation by
      glycosylation. Proteolytic processing regulates cytokine and chemokine
      activities. In this study, we report that natural posttranslational
      citrullination or deimination alters the biological activities of the neutrophil
      chemoattractant and angiogenic cytokine CXCL8/interleukin-8 (IL-8).
      Citrullination of arginine in position 5 was discovered on 14% of natural
      leukocyte-derived CXCL8(1-77), generating CXCL8(1-77)Cit(5). Peptidylarginine
      deiminase (PAD) is known to citrullinate structural proteins, and it may initiate
      autoimmune diseases. PAD efficiently and site-specifically citrullinated CXCL5,
      CXCL8, CCL17, CCL26, but not IL-1beta. In comparison with CXCL8(1-77), CXCL8(1
      77)Cit(5) had reduced affinity for glycosaminoglycans and induced less CXCR2
      dependent calcium signaling and extracellular signal-regulated kinase 1/2
      phosphorylation. In contrast to CXCL8(1-77), CXCL8(1-77)Cit(5) was resistant to
      thrombin- or plasmin-dependent potentiation into CXCL8(6-77). Upon
      intraperitoneal injection, CXCL8(6-77) was a more potent inducer of neutrophil
      extravasation compared with CXCL8(1-77). Despite its retained chemotactic
      activity in vitro, CXCL8(1-77)Cit(5) was unable to attract neutrophils to the
      peritoneum. Finally, in the rabbit cornea angiogenesis assay, the equally potent
      CXCL8(1-77) and CXCL8(1-77)Cit(5) were less efficient angiogenic molecules than
      CXCL8(6-77). This study shows that PAD citrullinates the chemokine CXCL8, and
      thus may dampen neutrophil extravasation during acute or chronic inflammation.

PMID- 18710931
TI  - CD4+ FoxP3+ regulatory T cells confer infectious tolerance in a TGF-beta
      dependent manner.
AB  - CD4(+)FoxP3(+) regulatory T (T reg) cells comprise a separate lineage of T cells
      that are essential for maintaining immunological tolerance to self. The molecular
      mechanism(s) by which T reg cells mediate their suppressive effects remains
      poorly understood. One molecule that has been extensively studied in T reg cell
      suppression is transforming growth factor (TGF)-beta, but its importance remains
      controversial. We found that TGF-beta complexed to latency-associated peptide
      (LAP) is expressed on the cell surface of activated but not resting T reg cells.
      T reg cell LAP-TGF-beta plays an important role in the suppression of the
      proliferation of activated T cells, but it is not required for the suppression of
      naive T cell activation. More importantly, T reg cell-derived TGF-beta could
      generate de novo CD4(+)FoxP3(+) T cells in vitro from naive precursors in a cell
      contact-dependent, antigen-presenting cell-independent and alpha(V) integrin
      independent manner. The newly induced CD4(+)FoxP3(+) T cells are suppressive both
      in vitro and in vivo. Transfer of activated antigen-specific T reg cells with
      naive antigen-specific responder T cells to normal recipients, followed by
      immunization, also results in induction of FoxP3 expression in the responder
      cells. T reg cell-mediated generation of functional CD4(+)FoxP3(+) cells via this
      TGF-beta-dependent pathway may represent a major mechanism as to how T reg cells
      maintain tolerance and expand their suppressive abilities.

PMID- 18710932
TI  - Small intestinal CD103+ dendritic cells display unique functional properties that
      are conserved between mice and humans.
AB  - A functionally distinct subset of CD103(+) dendritic cells (DCs) has recently
      been identified in murine mesenteric lymph nodes (MLN) that induces enhanced
      FoxP3(+) T cell differentiation, retinoic acid receptor signaling, and gut-homing
      receptor (CCR9 and alpha4beta7) expression in responding T cells. We show that
      this function is specific to small intestinal lamina propria (SI-LP) and MLN
      CD103(+) DCs. CD103(+) SI-LP DCs appeared to derive from circulating DC
      precursors that continually seed the SI-LP. BrdU pulse-chase experiments
      suggested that most CD103(+) DCs do not derive from a CD103(-) SI-LP DC
      intermediate. The majority of CD103(+) MLN DCs appear to represent a tissue
      derived migratory population that plays a central role in presenting orally
      derived soluble antigen to CD8(+) and CD4(+) T cells. In contrast, most CD103(-)
      MLN DCs appear to derive from blood precursors, and these cells could proliferate
      within the MLN and present systemic soluble antigen. Critically, CD103(+) DCs
      with similar phenotype and functional properties were present in human MLN, and
      their selective ability to induce CCR9 was maintained by CD103(+) MLN DCs
      isolated from SB Crohn's patients. Thus, small intestinal CD103(+) DCs represent
      a potential novel target for regulating human intestinal inflammatory responses.

PMID- 18710933
TI  - Repertoire-based selection into the marginal zone compartment during B cell
      development.
AB  - Marginal zone (MZ) B cells resemble fetally derived B1 B cells in their innate
      like rapid responses to bacterial pathogens, but the basis for this is unknown.
      We report that the MZ is enriched in "fetal-type" B cell receptors lacking N
      regions (N(-)). Mixed bone marrow (BM) chimeras, made with adult terminal
      deoxynucleotidyl transferase (TdT)(+/+) and TdT(-/-) donor cells, demonstrate
      preferential repertoire-based selection of N(-) B cells into the MZ.
      Reconstitution of irradiated mice with adult TdT(+/+) BM reveals that the MZ can
      replenish N(-) B cells in adult life via repertoire-based selection and suggest
      the possibility of a TdT-deficient precursor population in the adult BM. The
      mixed chimera data also suggest repertoire-based bifurcations into distinct BM
      and splenic maturation pathways, with mature "recirculating" BM B cells showing a
      very strong preference for N(+) complementarity-determining region (CDR) 3
      compared with follicular B cells. Because the T1 and MZ compartments are both the
      most enriched for N(-) H-CDR3, we propose a novel direct T1-->MZ pathway and
      identify a potential T1-MZ precursor intermediate. We demonstrate progressive but
      discontinuous repertoire-based selection throughout B cell development supporting
      multiple branchpoints and pathways in B cell development. Multiple
      differentiation routes leading to MZ development may contribute to the reported
      functional heterogeneity of the MZ compartment.

PMID- 18710934
TI  - The association of Notch2 and NF-kappaB accelerates RANKL-induced
      osteoclastogenesis.
AB  - Notch signaling plays a key role in various cell differentiation processes
      including bone homeostasis. However, the specific involvement of Notch in
      regulating osteoclastogenesis is still controversial. In the present study, we
      show that RANKL induces expression of Jagged1 and Notch2 in bone marrow
      macrophages during osteoclast differentiation. Suppression of Notch signaling by
      a selective gamma-secretase inhibitor or Notch2 short hairpin RNA suppresses
      RANKL-induced osteoclastogenesis. In contrast, induction of Notch signaling by
      Jagged1 or by ectopic expression of intracellular Notch2 enhances NFATc1 promoter
      activity and expression and promotes osteoclastogenesis. Finally, we found that
      Notch2 and p65 interact in the nuclei of RANKL-stimulated cells and that both
      proteins are recruited to the NFATc1 promoter, driving its expression. Taken
      together, our results show a new molecular cross talk between Notch and NF-kappaB
      pathways that is relevant in osteoclastogenesis.

PMID- 18710935
TI  - The histone acetyltransferase PCAF associates with actin and hnRNP U for RNA
      polymerase II transcription.
AB  - Actin is a key regulator of RNA polymerase (pol) II transcription. In complex
      with specific hnRNPs, it has been proposed that actin functions to recruit pol II
      coactivators during the elongation of nascent transcripts. Here, we show by
      affinity chromatography, protein-protein interaction assays, and biochemical
      fractionation of nuclear extracts that the histone acetyltransferase (HAT) PCAF
      associates with actin and hnRNP U. PCAF and the nuclear actin-associated HAT
      activity detected in the DNase I-bound protein fraction could be released by
      disruption of the actin-hnRNP U complex. In addition, actin, hnRNP U, and PCAF
      were found to be associated with the Ser2/5- and Ser2-phosphorylated pol II
      carboxy-terminal domain construct. Chromatin and RNA immunoprecipitation assays
      demonstrated that actin, hnRNP U, and PCAF are present at the promoters and
      coding regions of constitutively expressed pol II genes and that they are
      associated with ribonucleoprotein complexes. Finally, disruption of the actin
      hnRNP U interaction repressed bromouridine triphosphate incorporation in living
      cells, suggesting that actin and hnRNP U cooperate with PCAF in the regulation of
      pol II transcription elongation.

PMID- 18710936
TI  - Disease-associated human telomerase RNA variants show loss of function for
      telomere synthesis without dominant-negative interference.
AB  - Telomerase adds simple-sequence repeats to chromosome ends to offset the terminal
      sequence loss inherent in each cycle of genome replication. Inherited mutations
      in genes encoding subunits of the human telomerase holoenzyme give rise to
      disease phenotypes including hematopoietic failure and pulmonary fibrosis.
      Disease-associated variants of the human telomerase RNA are expressed in
      heterozygous combination with wild-type telomerase RNA. Here, we exploit a
      sensitized human primary cell assay system to investigate the biological function
      of disease-linked telomerase RNA variants and their impact on the function of
      coexpressed wild-type telomerase RNA. We find that telomerase RNA variants
      discovered in patients with dyskeratosis congenita or aplastic anemia show loss
      of function without any indication of dominant-negative impact on telomere
      maintenance by the coexpressed wild-type RNA. To reconcile this result with
      contradictory findings from reconstitution assays in vitro, we demonstrate that
      the lack of dominant-negative impact on telomere maintenance correlates with
      physiological assembly of active human telomerase holoenzyme ribonucleoproteins
      harboring monomers rather than higher-order multimers of telomerase RNA and
      telomerase reverse transcriptase. These findings support loss of function of
      telomerase RNA as a general mechanism of human disease.

PMID- 18710937
TI  - A novel nuclear signaling pathway for thromboxane A2 receptors in
      oligodendrocytes: evidence for signaling compartmentalization during
      differentiation.
AB  - The present study investigated G protein expression, localization, and functional
      coupling to thromboxane A(2) receptors (TPRs) during oligodendrocyte (OLG)
      development. It was found that as OLGs mature, the expression levels of G(q)
      increase while those of G(13) decrease. In contrast, the expression levels of
      G(s), G(o), and G(i) do not change significantly. Localization studies revealed
      that G(q), G(13), and G(i) are present only in the extranuclear compartment,
      whereas G(s) and G(o) are found in both the extranuclear and the nuclear
      compartments. Purification of TPR-G protein complexes demonstrated that TPRs
      couple to both G(q) and G(13) in the extranuclear compartment but only to G(s) in
      the nuclear compartment. Furthermore, functional analysis revealed that
      stimulation of nuclear TPR in OLGs stimulates CREB phosphorylation and myelin
      basic protein transcription and increases survival. Collectively, these results
      demonstrate that (i) OLGs selectively modulate the expression of certain G
      proteins during development, (ii) G proteins are differentially localized in OLGs
      leading to subcellular compartmentalization, (iii) TPRs couple to G(q) and G(13)
      in the extranuclear compartment and to G(s) only in the nucleus, (iv) mature OLGs
      have a functional nuclear TPR-G(s) signaling pathway, and (v) nuclear TPR
      signaling can stimulate CREB phosphorylation and myelin gene transcription and
      increase cell survival. These findings represent a novel paradigm for selective
      modulation of G protein-coupled receptor-G protein signaling during cell
      development.

PMID- 18710938
TI  - Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells.
AB  - Oct4 and Sox2 are transcription factors required for pluripotency during early
      embryogenesis and for the maintenance of embryonic stem cell (ESC) identity.
      Functional mechanisms contributing to pluripotency are expected to be associated
      with genes transcriptionally activated by these factors. Here, we show that Oct4
      and Sox2 bind to a conserved promoter region of miR-302, a cluster of eight
      microRNAs expressed specifically in ESCs and pluripotent cells. The expression of
      miR-302a is dependent on Oct4/Sox2 in human ESCs (hESCs), and miR-302a is
      expressed at the same developmental stages and in the same tissues as Oct4 during
      embryogenesis. miR-302a is predicted to target many cell cycle regulators, and
      the expression of miR-302a in primary and transformed cell lines promotes an
      increase in S-phase and a decrease in G(1)-phase cells, reminiscent of an ESC
      like cell cycle profile. Correspondingly, the inhibition of miR-302 causes hESCs
      to accumulate in G(1) phase. Moreover, we show that miR-302a represses the
      productive translation of an important G(1) regulator, cyclin D1, in hESCs. The
      transcriptional activation of miR-302 and the translational repression of its
      targets, such as cyclin D1, may provide a link between Oct4/Sox2 and cell cycle
      regulation in pluripotent cells.

PMID- 18710939
TI  - Quantitative proteomic identification of MAZ as a transcriptional regulator of
      muscle-specific genes in skeletal and cardiac myocytes.
AB  - We identified a conserved sequence within the Muscle creatine kinase (MCK)
      promoter that is critical for high-level activity in skeletal and cardiac
      myocytes (MCK Promoter Element X [MPEX]). After selectively enriching for MPEX
      binding factor(s) (MPEX-BFs), ICAT-based quantitative proteomics was used to
      identify MPEX-BF candidates, one of which was MAZ (Myc-associated zinc finger
      protein). MAZ transactivates the MCK promoter and binds the MPEX site in vitro,
      and chromatin immunoprecipitation analysis demonstrates enrichment of MAZ at the
      endogenous MCK promoter and other muscle gene promoters (Skeletal alpha-actin,
      Desmin, and alpha-Myosin heavy chain) in skeletal and cardiac myocytes.
      Consistent with its role in muscle gene transcription, MAZ transcripts and DNA
      binding activity are upregulated during skeletal myocyte differentiation.
      Furthermore, MAZ was shown to bind numerous sequences (e.g., CTCCTCCC and
      CTCCACCC) that diverge from the GA box binding motif. Alternate motifs were
      identified in many muscle promoters, including Myogenin and MEF2C, and one motif
      was shown to be critical for Six4 promoter activity in both skeletal and cardiac
      myocytes. Interestingly, MAZ occupies and is able to transactivate the Six4
      promoter in skeletal but not cardiac myocytes. Taken together, these findings are
      consistent with a previously unrecognized role for MAZ in muscle gene regulation.

PMID- 18710940
TI  - An allelic series uncovers novel roles of the BRCT domain-containing protein PTIP
      in mouse embryonic vascular development.
AB  - Pax transactivation domain-interacting protein (PTIP, or PAXIP1) is required for
      mouse development and has been implicated in DNA damage responses and histone
      modification. However, the physiological roles of PTIP during embryogenesis
      remain unclear due to early embryonic lethality of null mutants. We describe two
      N-ethyl N-nitrosourea-induced hypomorphic missense alleles of Ptip, each of which
      alters one of the six encoded BRCT domains. Phenotypic characterization of these
      mutants revealed important functions of PTIP in vasculogenesis and
      chorioplacental development that appear unrelated to activities in DNA repair or
      global histone modification. The results of gene expression profiling and in
      vitro angiogenesis assays indicated that PTIP modulates a transcriptional
      program, centered around Vegfa, that drives the migration of endothelial cells to
      properly form the embryonic vasculature. These and other data suggest that PTIP
      has multiple functions, one of which is to promote the formation of
      transcriptional complexes that provide specificity of developmental gene
      expression.

PMID- 18710941
TI  - A role for DEAD box 1 at DNA double-strand breaks.
AB  - DEAD box proteins are a family of putative RNA helicases associated with all
      aspects of cellular metabolism involving the modification of RNA secondary
      structure. DDX1 is a member of the DEAD box protein family that is overexpressed
      in a subset of retinoblastoma and neuroblastoma cell lines and tumors. DDX1 is
      found primarily in the nucleus, where it forms two to four large aggregates
      called DDX1 bodies. Here, we report a rapid redistribution of DDX1 in cells
      exposed to ionizing radiation, resulting in the formation of numerous foci that
      colocalize with gamma-H2AX and phosphorylated ATM foci at sites of DNA double
      strand breaks (DSBs). The formation of DDX1 ionizing-radiation-induced foci
      (IRIF) is dependent on ATM, which was shown to phosphorylate DDX1 both in vitro
      and in vivo. The treatment of cells with RNase H prevented the formation of DDX1
      IRIF, suggesting that DDX1 is recruited to sites of DNA damage containing RNA-DNA
      structures. We have shown that DDX1 has RNase activity toward single-stranded
      RNA, as well as ADP-dependent RNA-DNA- and RNA-RNA-unwinding activities. We
      propose that DDX1 plays an RNA clearance role at DSB sites, thereby facilitating
      the template-guided repair of transcriptionally active regions of the genome.

PMID- 18710942
TI  - Deletion of Mtg16, a target of t(16;21), alters hematopoietic progenitor cell
      proliferation and lineage allocation.
AB  - While a number of DNA binding transcription factors have been identified that
      control hematopoietic cell fate decisions, only a limited number of
      transcriptional corepressors (e.g., the retinoblastoma protein [pRB] and the
      nuclear hormone corepressor [N-CoR]) have been linked to these functions. Here,
      we show that the transcriptional corepressor Mtg16 (myeloid translocation gene on
      chromosome 16), which is targeted by t(16;21) in acute myeloid leukemia, is
      required for hematopoietic progenitor cell fate decisions and for early
      progenitor cell proliferation. Inactivation of Mtg16 skewed early myeloid
      progenitor cells toward the granulocytic/macrophage lineage while reducing the
      numbers of megakaryocyte-erythroid progenitor cells. In addition, inactivation of
      Mtg16 impaired the rapid expansion of short-term stem cells, multipotent
      progenitor cells, and megakaryocyte-erythroid progenitor cells that is required
      under hematopoietic stress/emergency. This impairment appears to be a failure to
      proliferate rather than an induction of cell death, as expression of c-Myc, but
      not Bcl2, complemented the Mtg16(-/-) defect.

PMID- 18710943
TI  - Epidermal growth factor receptor 1 (EGFR1) and its variant EGFRvIII regulate TATA
      binding protein expression through distinct pathways.
AB  - The epidermal growth factor receptor (EGFR) family regulates essential biological
      processes. Various epithelial tumors are linked to EGFR overexpression or
      expression of variant forms, such as the EGFR1 variant, EGFRvIII. Perturbations
      in expression of the transcription initiation factor, TATA-binding protein (TBP),
      alter cellular growth properties. Here we demonstrate that EGFR1 and EGFRvIII,
      but not HER2, induce TBP expression at a transcriptional level through distinct
      mechanisms. EGFR1 enhances the phosphorylation and function of Elk-1, recruiting
      it to the TBP promoter. In contrast, EGFRvIII robustly induces c-jun expression,
      stimulating recruitment of c-fos/c-jun to an overlapping AP-1 site. Enhancing c
      jun expression alone induces TBP promoter activity through the AP-1 site. To
      determine the underlying mechanism for differences in Elk-1 function and c-jun
      expression by these receptors, we inhibited the internalization of EGFR1.
      Persistent EGFR1 cell surface occupancy mimics EGFRvIII-mediated effects on Elk-1
      and c-jun and switches the requirement of Elk-1 to AP-1 for TBP promoter
      induction. Together, these studies define a new molecular mechanism for the
      regulation of TBP expression. In addition, we identify distinct molecular targets
      of EGFR1 and EGFRvIII and demonstrate the importance of receptor internalization
      in distinguishing their specific functions.

PMID- 18710944
TI  - SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells
      from stress-mediated cell death by deacetylation of Ku70.
AB  - There are seven SIRT isoforms in mammals, with diverse biological functions
      including gene regulation, metabolism, and apoptosis. Among them, SIRT3 is the
      only sirtuin whose increased expression has been shown to correlate with an
      extended life span in humans. In this study, we examined the role of SIRT3 in
      murine cardiomyocytes. We found that SIRT3 is a stress-responsive deacetylase and
      that its increased expression protects myocytes from genotoxic and oxidative
      stress-mediated cell death. We show that, like human SIRT3, mouse SIRT3 is
      expressed in two forms, a approximately 44-kDa long form and a approximately 28
      kDa short form. Whereas the long form is localized in the mitochondria, nucleus,
      and cytoplasm, the short form is localized exclusively in the mitochondria of
      cardiomyocytes. During stress, SIRT3 levels are increased not only in
      mitochondria but also in the nuclei of cardiomyocytes. We also identified Ku70 as
      a new target of SIRT3. SIRT3 physically binds to Ku70 and deacetylates it, and
      this promotes interaction of Ku70 with the proapoptotic protein Bax. Thus, under
      stress conditions, increased expression of SIRT3 protects cardiomyocytes, in part
      by hindering the translocation of Bax to mitochondria. These studies underscore
      an essential role of SIRT3 in the survival of cardiomyocytes in stress
      situations.

PMID- 18710945
TI  - Regulation of the endosomal SNARE protein syntaxin 7 by colony-stimulating factor
      1 in macrophages.
AB  - Colony-stimulating factor 1 (CSF-1) is the main growth factor controlling the
      development of macrophages from myeloid progenitor cells. However, CSF-1 also
      regulates some of the key effector functions of macrophages (e.g., phagocytosis
      and cytokine secretion). The endosomal SNARE protein syntaxin 7 (Stx7) regulates
      vesicle trafficking events involved in phagocytosis and cytokine secretion.
      Therefore, we investigated the ability of CSF-1 to regulate Stx7. CSF-1
      upregulated Stx7 expression in primary mouse macrophages; it also upregulated
      expression of its SNARE partners Vti1b and VAMP8 but not Stx8. Additionally, CSF
      1 induced the rapid serine phosphorylation of Stx7 and enhanced its binding to
      Vti1b, Stx8, and VAMP8. Bioinformatics analysis and results from experiments with
      kinase inhibitors suggested the CSF-1-induced phosphorylation of Stx7 was
      mediated by protein kinase C and Akt in response to phosphatidylinositol 3-kinase
      activation. Based on mutagenesis studies, CSF-1 appeared to increase the binding
      of Stx7 to its SNARE partners by inducing the phosphorylation of serine residues
      in the Habc domain and/or "linker" region of Stx7. Thus, CSF-1 is a key regulator
      of Stx7 expression and function in macrophages. Furthermore, the effects of CSF-1
      on Stx7 may provide a mechanism for the regulation of macrophage effector
      functions by CSF-1.

PMID- 18710946
TI  - Acetylation of EKLF is essential for epigenetic modification and transcriptional
      activation of the beta-globin locus.
AB  - Posttranslational modifications of transcription factors provide alternate
      protein interaction platforms that lead to varied downstream effects. We have
      investigated how the acetylation of EKLF plays a role in its ability to alter the
      beta-like globin locus chromatin structure and activate transcription of the
      adult beta-globin gene. By establishing an EKLF-null erythroid line whose closed
      beta-locus chromatin structure and silent beta-globin gene status can be rescued
      by retroviral infection of EKLF, we demonstrate the importance of EKLF
      acetylation at lysine 288 in the recruitment of CBP to the locus, modification of
      histone H3, occupancy by EKLF, opening of the chromatin structure, and
      transcription of adult beta-globin. We also find that EKLF helps to coordinate
      this process by the specific association of its zinc finger domain with the
      histone H3 amino terminus. Although EKLF interacts equally well with H3.1 and
      H3.3, we find that only H3.3 is enriched at the adult beta-globin promoter. These
      data emphasize the critical nature of lysine acetylation in transcription factor
      activity and enable us to propose a model of how modified EKLF integrates
      coactivators, chromatin remodelers, and nucleosomal components to alter
      epigenetic chromatin structure and stimulate transcription.

PMID- 18710947
TI  - Lactate stimulates vasculogenic stem cells via the thioredoxin system and engages
      an autocrine activation loop involving hypoxia-inducible factor 1.
AB  - The recruitment and differentiation of circulating stem/progenitor cells (SPCs)
      in subcutaneous Matrigel in mice was assessed. There were over one million
      CD34(+) SPCs per Matrigel plug 18 h after Matrigel implantation, and including a
      polymer to elevate the lactate concentration increased the number of SPCs by 3.6
      fold. Intricate CD34(+) cell-lined channels were linked to the systemic
      circulation, and lactate accelerated cell differentiation as evaluated based on
      surface marker expression and cell cycle entry. CD34(+) SPCs from lactate
      supplemented Matrigel exhibited significantly higher concentrations of
      thioredoxin 1 (Trx1) and hypoxia-inducible factor 1 (HIF-1) than cells from
      unsupplemented Matrigel, whereas Trx1 and HIF-1 in CD45(+) leukocytes were not
      elevated by lactate. Results obtained using small inhibitory RNA (siRNA) specific
      to HIF-1 and mice with conditionally HIF-1 null myeloid cells indicated that SPC
      recruitment and lactate-mediated effects were dependent on HIF-1. Cells from
      lactate-supplemented Matrigel had higher concentrations of phosphorylated
      extracellular signal-regulated kinases 1 and 2, Trx1, Trx reductase (TrxR),
      vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF
      1) than cells from unsupplemented Matrigel. SPC recruitment and protein changes
      were inhibited by siRNA specific to lactate dehydrogenase, TrxR, or HIF-1 and by
      oxamate, apocynin, U0126, N-acetylcysteine, dithioerythritol, and antibodies to
      VEGF or SDF-1. Oxidative stress from lactate metabolism by SPCs accelerated
      further SPC recruitment and differentiation through Trx1-mediated elevations in
      HIF-1 levels and the subsequent synthesis of HIF-1-dependent growth factors.

PMID- 18710948
TI  - TRAF6 and the three C-terminal lysine sites on IRF7 are required for its
      ubiquitination-mediated activation by the tumor necrosis factor receptor family
      member latent membrane protein 1.
AB  - We have recently shown that interferon regulatory factor 7 (IRF7) is activated by
      Epstein-Barr virus latent membrane protein 1 (LMP1), a member of the tumor
      necrosis factor receptor (TNFR) superfamily, through receptor-interacting protein
      dependent K63-linked ubiquitination (L. E. Huye, S. Ning, M. Kelliher, and J. S.
      Pagano, Mol. Cell. Biol. 27:2910-2918, 2007). In this study, with the use of
      small interfering RNA and TNFR-associated factor 6 (TRAF6) knockout cells, we
      first show that TRAF6 and its E3 ligase activity are required for LMP1-stimulated
      IRF7 ubiquitination. In Raji cells which are latently infected and express high
      levels of LMP1 and IRF7 endogenously, expression of a TRAF6 small hairpin RNA
      construct reduces endogenous ubiquitination and endogenous activity of IRF7. In
      TRAF6(-/-) mouse embryonic fibroblasts, reconstitution with TRAF6 expression, but
      not with TRAF6(C70A), which lacks the E3 ligase activity, recovers LMP1's ability
      to stimulate K63-linked ubiquitination of IRF7. Further, we identify IRF7 as a
      substrate for TRAF6 E3 ligase and show that IRF7 is ubiquitinated by TRAF6 at
      multiple sites both in vitro and in vivo. Most important, we determine that the
      last three C-terminal lysine sites (positions 444, 446, and 452) of human IRF7
      variant A are essential for activation of IRF7; these are the first such sites
      identified. A ubiquitination-deficient mutant of IRF7 with these sites mutated to
      arginines completely loses transactivational ability in response not only to LMP1
      but also to the IRF7 kinase IkappaB kinase epsilon. In addition, we find that K63
      linked ubiquitination of IRF7 occurs independently of its C-terminal functional
      phosphorylation sites. These data support our hypothesis that regulatory
      ubiquitination of IRF7 is a prerequisite for its phosphorylation. This is the
      first evidence to imply that ubiquitination is required for phosphorylation and
      activation of a transcription factor.

PMID- 18710949
TI  - Phosphorylation of p27Kip1 regulates assembly and activation of cyclin D1-Cdk4.
AB  - p27 mediates Cdk2 inhibition and is also found in cyclin D1-Cdk4 complexes. The
      present data support a role for p27 in the assembly of D-type cyclin-Cdk
      complexes and indicate that both cyclin D1-Cdk4-p27 assembly and kinase
      activation are regulated by p27 phosphorylation. Prior work showed that p27 can
      be phosphorylated by protein kinase B/Akt (PKB/Akt) at T157 and T198. Here we
      show that PKB activation and the appearance of p27pT157 and p27pT198 precede p27
      cyclin D1-Cdk4 assembly in early G(1). PI3K/PKB inhibition rapidly reduced
      p27pT157 and p27pT198 and dissociated cellular p27-cyclin D1-Cdk4. Mutant p27
      allele products lacking phosphorylation at T157 and T198 bound poorly to cellular
      cyclin D1 and Cdk4. Cellular p27pT157 and p27pT198 coprecipitated with Cdk4 but
      were not detected in Cdk2 complexes. The addition of p27 to recombinant cyclin D1
      and Cdk4 led to cyclin D1-Cdk4-p27 complex formation in vitro. p27
      phosphorylation by PKB increased p27-cyclin D1-Cdk4 assembly in vitro but yielded
      inactive Cdk4. In contrast, Src pretreatment of p27 did not affect p27-cyclin D1
      Cdk4 complex formation. However, Src treatment led to tyrosine phosphorylation of
      p27 and catalytic activation of assembled cyclin D1-Cdk4-p27 complexes. Thus,
      while PKB-dependent p27 phosphorylation appears to increase cyclin D1-Cdk4-p27
      assembly or stabilize these complexes in vitro, cyclin D1-Cdk4-p27 activation
      requires the tyrosine phosphorylation of p27. Constitutive activation of PKB and
      Abl or Src family kinases in cancers would drive p27 phosphorylation, increase
      cyclin D1-Cdk4 assembly and activation, and reduce the cyclin E-Cdk2 inhibitory
      function of p27. Combined therapy with both Src and PI3K/PKB inhibitors may
      reverse this process.

PMID- 18710950
TI  - Effects of the SANT domain of tension-induced/inhibited proteins (TIPs), novel
      partners of the histone acetyltransferase p300, on p300 activity and TIP-6
      induced adipogenesis.
AB  - We previously identified a set of transcription regulators, referred to as TIPs
      (tension-induced/inhibited proteins), with a role in myogenic versus adipogenic
      differentiation. Here we report that the TIP family comprises eight isoforms, all
      bearing a SANT (switching-defective protein 3, adaptor 2, nuclear receptor
      corepressor, and transcription factor IIIB) domain and some of them presenting S
      adenosyl-l-methionine (SAM) and nuclear receptor box (NRB) motifs, all
      characteristic of histone-modifying enzymatic complexes. TIPs have SANT
      dependent, p300-mediated histone acetyltransferase (HAT) activity. Ectopic TIP-6
      (SANT(+) SAM(-) NRB(-)) but not TIP-6DeltaSANT induced de novo PPARgamma2
      mediated adipogenic gene expression in NIH 3T3 cells and promoted preadipocyte
      differentiation into fat cells. TIP-6 was also involved in mediating
      hormonally/biochemically induced adipogenic differentiation of 3T3-L1 cells.
      Furthermore, TIP-6 was identified in adipose tissue in vivo. TIP-6 bound directly
      and indirectly to p300 and histone H4 (H4). Deletion of the SANT domain did not
      abolish TIP-6 interaction with p300 and H4 but eliminated direct TIP-6 binding to
      p300. Chromatin immunoprecipitation assays showed the recruitment of TIP-6, TIP
      6DeltaSANT, and p300 to the PPARgamma2 promoter, but H3/H4 acetylation occurred
      only when p300 was directly associated with TIP-6. These studies demonstrated the
      importance of TIPs in the recruitment of p300 to specific promoters and in the
      regulation of p300 HAT activity through the involvement of the SANT domain.
      Furthermore, we identified TIP-6 as a new member of the adipogenic cascade.

PMID- 18710951
TI  - OTT-MAL is a deregulated activator of serum response factor-dependent gene
      expression.
AB  - The OTT-MAL/RBM15-MKL1 fusion protein is the result of the recurrent
      translocation t(1;22) in acute megakaryocytic leukemia in infants. How it
      contributes to the malignancy is unknown. The 3' fusion partner, MAL/MKL1/MRTF-A,
      is a transcriptional coactivator of serum response factor (SRF). MAL plays a key
      role in regulated gene expression depending on Rho family GTPases and G-actin.
      Here we demonstrate that OTT-MAL is a constitutive activator of SRF and target
      gene expression. This requires the SRF-binding motif and the MAL-derived
      transactivation domain. OTT-MAL localizes to the nucleus and is not regulated by
      upstream signaling. OTT-MAL deregulation reflects its independence from control
      by G-actin, which fails to interact with OTT-MAL in coimmunoprecipitation
      experiments. Regulation cannot be restored by reintroduction of the entire MAL N
      terminus into the fusion protein. OTT-MAL also caused a delayed induction of the
      MAL-independent, ternary complex factor-dependent target genes c-fos and egr-1
      and the mitogen-activated protein kinase/Erk pathway. With testing in
      heterologous tissue culture systems, however, we observed considerable
      antiproliferative effects of OTT-MAL. Our data suggest that the deregulated
      activation of MAL-dependent and -independent promoters results in tissue-specific
      functions of OTT-MAL.

PMID- 18710952
TI  - The catalytic subunit of DNA-dependent protein kinase regulates proliferation,
      telomere length, and genomic stability in human somatic cells.
AB  - The DNA-dependent protein kinase (DNA-PK) complex is a serine/threonine protein
      kinase comprised of a 469-kDa catalytic subunit (DNA-PK(cs)) and the DNA binding
      regulatory heterodimeric (Ku70/Ku86) complex Ku. DNA-PK functions in the
      nonhomologous end-joining pathway for the repair of DNA double-stranded breaks
      (DSBs) introduced by either exogenous DNA damage or endogenous processes, such as
      lymphoid V(D)J recombination. Not surprisingly, mutations in Ku70, Ku86, or DNA
      PK(cs) result in animals that are sensitive to agents that cause DSBs and that
      are also immune deficient. While these phenotypes have been validated in several
      model systems, an extension of them to humans has been missing due to the lack of
      patients with mutations in any one of the three DNA-PK subunits. The worldwide
      lack of patients suggests that during mammalian evolution this complex has become
      uniquely essential in primates. This hypothesis was substantiated by the
      demonstration that functional inactivation of either Ku70 or Ku86 in human
      somatic cell lines is lethal. Here we report on the functional inactivation of
      DNA-PK(cs) in human somatic cells. Surprisingly, DNA-PK(cs) does not appear to be
      essential, although the cell line lacking this gene has profound proliferation
      and genomic stability deficits not observed for other mammalian systems.

PMID- 18710953
TI  - Loss of the epigenetic tumor suppressor SNF5 leads to cancer without genomic
      instability.
AB  - There is a growing appreciation of the role that epigenetic alterations can play
      in oncogenesis. However, given the large number of genetic anomalies present in
      most cancers, it has been difficult to evaluate the extent to which epigenetic
      changes contribute to cancer. SNF5 (INI1/SMARCB1/BAF47) is a tumor suppressor
      that regulates the epigenome as a core member of the SWI/SNF chromatin remodeling
      complex. While the SWI/SNF complex displays potent tumor suppressor activity, it
      is unknown whether this activity is exerted genetically via maintenance of genome
      integrity or epigenetically via transcriptional regulation. Here we show that
      Snf5-deficient primary cells do not show altered sensitivity to DNA damaging
      agents, defects in gamma-H2AX induction, or an abrogated DNA damage checkpoint.
      Further, the aggressive malignancies that arise following SNF5 loss are diploid
      and genomically stable. Remarkably, we demonstrate that most human SNF5-deficient
      cancers lack genomic amplifications/deletions and, aside from SNF5 loss, are
      indistinguishable from normal cells on single-nucleotide polymorphism arrays.
      Finally, we show that epigenetically based changes in transcription that occur
      following SNF5 loss correlate with the tumor phenotype. Collectively, our results
      provide novel insight into the mechanisms of oncogenesis by demonstrating that
      disruption of a chromatin remodeling complex can largely, if not completely,
      substitute for genomic instability in the genesis of aggressive cancer.

PMID- 18710954
TI  - Distinct malaria parasite sporozoites reveal transcriptional changes that cause
      differential tissue infection competence in the mosquito vector and mammalian
      host.
AB  - The malaria parasite sporozoite transmission stage develops and differentiates
      within parasite oocysts on the Anopheles mosquito midgut. Successful inoculation
      of the parasite into a mammalian host is critically dependent on the sporozoite's
      ability to first infect the mosquito salivary glands. Remarkable changes in
      tissue infection competence are observed as the sporozoites transit from the
      midgut oocysts to the salivary glands. Our microarray analysis shows that
      compared to oocyst sporozoites, salivary gland sporozoites upregulate expression
      of at least 124 unique genes. Conversely, oocyst sporozoites show upregulation of
      at least 47 genes (upregulated in oocyst sporozoites [UOS genes]) before they
      infect the salivary glands. Targeted gene deletion of UOS3, encoding a putative
      transmembrane protein with a thrombospondin repeat that localizes to the
      sporozoite secretory organelles, rendered oocyst sporozoites unable to infect the
      mosquito salivary glands but maintained the parasites' liver infection
      competence. This phenotype demonstrates the significance of differential UOS
      expression. Thus, the UIS-UOS gene classification provides a framework to
      elucidate the infectivity and transmission success of Plasmodium sporozoites on a
      whole-genome scale. Genes identified herein might represent targets for vector
      based transmission blocking strategies (UOS genes), as well as strategies that
      prevent mammalian host infection (UIS genes).

PMID- 18710956
TI  - Differentiating between substantiated, suspected, and unsubstantiated
      maltreatment in Canada.
AB  - The decision to substantiate is a key factor in determining eligibility for
      services and decisions to press criminal charges or to remove a child, and it is
      frequently the basis for selecting samples of maltreated children or to measure
      recidivism or intervention effectiveness. Although there is a growing body of
      research on case substantiation in the United States, few studies have examined
      this decision in other jurisdictions. Using data from the 2003 Canadian Incidence
      Study of Reported Child Abuse and Neglect, this study examines the profiles of a
      national sample of 10,010 investigations. Multivariate analyses reveal that
      substantiation decisions are generally made in a fashion that is relatively
      consistent with the clinical characteristics of cases. Along with severity of
      harm, parent risk factors, and housing risk factors, police referrals are among
      the most important predictors of case substantiation. Cases involving multiple
      forms of maltreatment are also more likely to be substantiated.

PMID- 18710955
TI  - Histone deacetylase inhibitors modify pancreatic cell fate determination and
      amplify endocrine progenitors.
AB  - During pancreas development, transcription factors play critical roles in
      exocrine and endocrine differentiation. Transcriptional regulation in eukaryotes
      occurs within chromatin and is influenced by posttranslational histone
      modifications (e.g., acetylation) involving histone deacetylases (HDACs). Here,
      we show that HDAC expression and activity are developmentally regulated in the
      embryonic rat pancreas. We discovered that pancreatic treatment with different
      HDAC inhibitors (HDACi) modified the timing and determination of pancreatic cell
      fate. HDACi modified the exocrine lineage via abolition and enhancement of acinar
      and ductal differentiation, respectively. Importantly, HDACi treatment promoted
      the NGN3 proendocrine lineage, leading to an increased pool of endocrine
      progenitors and modified endocrine subtype lineage choices. Interestingly,
      treatments with trichostatin A and sodium butyrate, two inhibitors of both class
      I and class II HDACs, enhanced the pool of beta cells. These results highlight
      the roles of HDACs at key points in exocrine and endocrine differentiation. They
      show the powerful use of HDACi to switch pancreatic cell determination and
      amplify specific cellular subtypes, with potential applications in cell
      replacement therapies in diabetes.

PMID- 18710959
TI  - Calcified vascular plaque specimens: assessment with cardiac dual-energy
      multidetector CT in anthropomorphically moving heart phantom.
AB  - PURPOSE: To evaluate whether dual-energy multidetector computed tomography (CT)
      with image postprocessing techniques enhances accuracy of calcified plaque
      quantification beyond the scope of single-energy multidetector CT, by using
      optical coherence tomography (OCT) as the reference standard. MATERIALS AND
      METHODS: Four atherosclerotic specimens were examined with 64-section dual-energy
      multidetector CT by using a novel dual-detector "double-decker" design, with
      stacked high- and low-energy detector arrays with 32 x 0.625-mm collimation, at
      140 kVp and 400 mAs, acquiring simultaneous and isopedic low- and high-energy
      data sets. Additionally, combined-energy data sets were calculated, and an
      enhancement algorithm was proposed. Cardiac motion was simulated by an
      anthropomorphically moving phantom, and OCT was used as a reference standard for
      plaque quantification. Univariate general linear model (GLM) analysis was used to
      compare sizes of plaque calcifications determined with OCT with those determined
      with dual-energy multidetector CT, and the significance of factors such as
      cardiac motion was assessed. RESULTS: GLM analysis revealed that plaque
      quantification based on low-, high-, and combined-energy data sets differed
      significantly from that based on OCT (P < .001). Greater data variation occurred
      in smaller (<8 mm(2)) and larger (>12 mm(2)) calcifications. Comparison of
      calcified plaque sizes determined with OCT with those determined with the dual
      energy multidetector CT enhancement algorithm revealed no significant difference
      (P = .550). Cardiac activity led to a slight increase in data variation in regard
      to OCT for corresponding static (mean, 10.2% +/- 3.2 [standard deviation]) and
      dynamic (13.8% +/- 4.9) dual-energy multidetector CT data sets. CONCLUSION: Dual
      energy multidetector CT with novel postprocessing techniques enhanced accuracy of
      calcified plaque quantification by reducing effects of tissue blooming and beam
      hardening beyond single-energy multidetector CT.

PMID- 18710960
TI  - Calcified plaque: measurement of area at thin-section flat-panel CT and 64
      section multidetector CT and comparison with histopathologic findings.
AB  - The purpose of this study was to assess the blooming artifacts in ex vivo
      coronary arteries at multidetector computed tomography (CT) and flat-panel-volume
      CT by comparing measured areas of calcified plaque with respect to the reference
      standard of histopathologic findings. Three ex vivo hearts were scanned with
      multidetector CT and flat-panel-volume CT after institutional review board
      approval. The area of calcified plaque was measured at histopathologic
      examination, multidetector CT, and flat-panel-volume CT. The plaque area was
      overestimated at multidetector CT by 400% (4.61/1.15) on average, and the
      predicted difference between the measurements was significant (3.46 mm(2), P =
      .018). The average overestimation of plaque area at flat-panel-volume CT was
      twofold (214% [2.18/1.02]), and the predicted difference was smaller (1.16 mm(2),
      P = .08). The extent of the blooming artifact in visualizing calcified coronary
      plaque is reduced by using flat-panel-volume CT.

PMID- 18710961
TI  - Localization of the appendix at MR imaging during pregnancy: utility of the cecal
      tilt angle.
AB  - PURPOSE: To determine whether the cecal tilt angle on sagittal magnetic resonance
      (MR) images in pregnant patients correlates with the location of the appendix and
      gestational age and whether the cecal tilt angle can help predict the location of
      the appendix. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was
      approved by the institutional review board. Informed consent was waived. Of 146
      consecutive pregnant patients suspected of having appendicitis (mean age, 29
      years) who underwent MR imaging, 143 had MR images in which the appendix and
      cecum were identifiable in the sagittal plane. Two observers reviewed the MR
      images; findings were agreed upon by consensus. With use of sagittal single-shot
      fast spin-echo MR images, the cecal tilt angle was calculated as the angle
      between the imaging table and a line drawn between the cecal tip and the luminal
      center of the most proximal inflection point in the ascending colon. The location
      of the appendiceal base relative to the lumbosacral spine was recorded.
      Statistical analyses were performed by using Spearman and Pearson correlation
      coefficients to evaluate the relationship among gestational age, appendiceal base
      location, and cecal tilt angle. Receiver operating characteristic curve analysis
      was performed to assess the ability of the cecal tilt angle to help differentiate
      between a high and low appendiceal base level. RESULTS: Cecal tilt angles showed
      moderate correlation with appendiceal base levels (Spearman correlation
      coefficient, 0.44; P < .001) and poor correlation with gestational age (Pearson
      correlation coefficient, 0.25; P = .002). Regardless of gestational age, cecal
      tilt angles of at least 90 degrees were predictive of a high appendiceal base
      level with a specificity of 98% (95% confidence interval: 92%, 100%). CONCLUSION:
      The cecal tilt angle is useful for localizing the appendix in pregnant patients
      at MR imaging and helps predict the location of the appendix within the right
      upper quadrant of the abdomen with high specificity, irrespective of gestational
      age.

PMID- 18710962
TI  - MR imaging evaluation of the normal appendix in children and adolescents.
AB  - PURPOSE: To evaluate asymptomatic children and adolescents to determine the rate
      of detection of the normal appendix at unenhanced magnetic resonance (MR)
      imaging. MATERIALS AND METHODS: This study was approved by the medical ethics
      committees of the authors' institutions, and informed consent was obtained from
      participants' parents or guardians. Forty asymptomatic volunteers underwent MR
      imaging to detect the appendix. Mean age (+/- standard deviation) for the 18 boys
      was 12.8 years +/- 2.4 (range, 9-17 years) and for the 22 girls was 12.7 years +/
      2.7 (range, 8-17 years). The MR imaging protocol consisted of axial T1-weighted
      fast spin-echo (SE), axial and coronal T2-weighted fast SE, and axial T2-weighted
      fat-saturated fast SE sequences. Two observers interpreted results independently,
      and kappa coefficients were calculated to evaluate agreement. The rate of
      detection was defined as the percentage of times that the appendix was visualized
      with at least one sequence. Body mass index was recorded for all participants.
      RESULTS: The normal appendix was detected by one observer in 19 cases (48%) and
      by the other in 20 cases (50%). The rate of appendix detection after observers
      reached a consensus was 48% (95% confidence interval: 32%, 64%). Interobserver
      agreement for appendix detection was good for most sequences analyzed. The
      greatest rate of normal appendix detection was found with the axial T2-weighted
      fast SE sequence (48%). CONCLUSION: The rate of normal appendix detection in
      children and adolescents at unenhanced MR imaging was 48%, which is similar to
      computed tomographic but lower than ultrasonographic detection rates.

PMID- 18710963
TI  - Detection and restaging of residual and/or recurrent nasopharyngeal carcinoma
      after chemotherapy and radiation therapy: comparison of MR imaging and FDG
      PET/CT.
AB  - PURPOSE: To compare the accuracy of magnetic resonance (MR) imaging and combined
      fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed
      tomography (CT), alone and in combination, in detection and restaging treated
      nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: This retrospective study
      was performed after institutional review board approval and informed consent were
      obtained. Sixty-three consecutive patients treated for NPC underwent follow-up
      with both MR imaging and FDG PET/CT. Findings were evaluated according to the TNM
      classification. Final diagnosis was confirmed at biopsy or imaging follow-up for
      at least 6 months. Proportions and their 95% confidence intervals were computed;
      for comparison of data obtained separately from MR imaging and FDG PET/CT and
      those obtained from their combined use, the McNemar test was used. P < .05 was
      considered to indicate a statistically significant difference. RESULTS: There was
      a trend toward greater overall accuracy of MR over PET/CT in detecting residual
      and/or recurrent NPC at the primary site; 92.1% (58 of 63 patients) for MR versus
      85.7% (54 of 63) for FDG PET/CT (P = .16). Overall accuracy for tumor restaging
      was 74.6% (47 of 63) for MR and 73.0% (46 of 63) for FDG PET/CT (either modality
      used alone), but the overall combined accuracy was 92.1% (58 of 63) (all P values
      < .01). CONCLUSION: MR imaging demonstrated a trend toward higher accuracy than
      did FDG PET/CT in detecting residual and/or recurrent NPC at the primary tumor
      site. The combined use of MR and FDG PET/CT was more accurate for tumor restaging
      than when either modality was used independently.

PMID- 18710965
TI  - In vivo quantification of cortical bone water with ultrashort echo-time MR
      imaging: a new parameter to measure bone quality?

PMID- 18710966
TI  - The new requirements and testing for American Board of Radiology certification in
      diagnostic radiology.

PMID- 18710967
TI  - The new requirements and testing for American Board of Radiology certification: a
      contrary opinion.

PMID- 18710968
TI  - STARD statement: still room for improvement in the reporting of diagnostic
      accuracy studies.

PMID- 18710969
TI  - The role of abdominal radiography in the evaluation of the nontrauma emergency
      patient: new thoughts on an old problem.

PMID- 18710970
TI  - Revised colorectal screening guidelines: joint effort of the American Cancer
      Society, U.S. Multisociety Task Force on Colorectal Cancer, and American College
      of Radiology.

PMID- 18710971
TI  - Net assets: special collections.

PMID- 18710972
TI  - Imaging of skull base cerebrospinal fluid leaks in adults.
AB  - Cerebrospinal fluid (CSF) leak occurs when there is an osseous and dural defect
      at the skull base, with direct communication of the subarachnoid space to the
      extracranial space, usually a paranasal sinus. Recognition of the leak site and
      source and appropriate treatment are necessary to avoid rhinorrhea or otorrhea,
      low-pressure headaches, and meningitis, known complications of CSF leak. The
      imaging evaluation has evolved over the past several decades. Description of
      current techniques available to direct treatment options, including multidetector
      thin-section computed tomography, and imaging recommendations are presented.

PMID- 18710973
TI  - Radiographic evaluation of arthritis: degenerative joint disease and variations.
AB  - In the presence of joint space narrowing, it is important to differentiate
      inflammatory from degenerative conditions. The presence of osteophytes, bone
      sclerosis, and subchondral cysts and the absence of inflammatory features such as
      erosions suggest osteoarthritis. Typical osteoarthritis involves specific joints
      at a particular patient age. When osteoarthritis involves an atypical joint,
      occurs at an early age, or has an unusual radiographic appearance, then other
      causes for cartilage destruction should be considered, such as trauma, crystal
      deposition, neuropathic joint, and hemophilia. There are several types of
      arthritis, such as juvenile chronic arthritis and gouty arthritis, that may have
      a variable appearance compared with that of other common inflammatory
      arthritides.

PMID- 18710974
TI  - Acute traumatic aortic injury: imaging evaluation and management.
AB  - Despite recent advances in prehospital care, multidetector computed tomographic
      (CT) technology, and rapid definitive therapy, trauma to the aorta continues to
      be a substantial source of morbidity and mortality in patients with blunt trauma.
      The imaging evaluation of acute aortic injuries has undergone radical change over
      the past decade, mostly due to the advent of multidetector CT. Regardless of
      recent technologic advances, imaging of the aorta in the trauma setting remains a
      multimodality imaging practice, and thus broad knowledge by the radiologist is
      essential. Likewise, the therapy for acute aortic injuries has changed
      substantially. Though open surgical repair continues to be the mainstay of
      therapy, percutaneous endovascular repair is becoming commonplace in many trauma
      centers. Here, the historical and current status of imaging and therapy of acute
      traumatic aortic injuries will be reviewed.

PMID- 18710975
TI  - Optimal electrocardiographic pulsing windows and heart rate: effect on image
      quality and radiation exposure at dual-source coronary CT angiography.
AB  - PURPOSE: To determine the optimal width and timing of the electrocardiographic
      (ECG) pulsing window within the cardiac cycle in relation to heart rate (HR),
      image quality, and radiation exposure in patients who are suspected of having
      coronary artery disease. MATERIALS AND METHODS: The institutional review board
      approved the study, and all patients gave informed consent. Dual-source computed
      tomography (CT) was performed in 301 patients (mean HR, 70.1 beats per minute +/-
      13.3 [standard deviation]; range, 43-112 beats per minute) by using a wide ECG
      pulsing window (25%-70% of the R-R interval). Data sets were reconstructed in 5%
      steps from 20%-75% of R-R interval. Image quality was assessed by two observers
      on a per-segment level and was classified as good or impaired. High-quality data
      sets were those in which each segment was of good quality. The width and timing
      of the image reconstruction window was calculated. On the basis of these
      findings, an optimal HR-dependent ECG pulsing protocol was designed, and the
      potential dose-saving effect on effective dose (in millisieverts) was calculated.
      RESULTS: At low HR (< or = 65 beats per minute), high-quality data sets were
      obtained during end diastole (ED); at high HR (> or = 80 beats per minute), they
      were obtained during end systole (ES); and at intermediate HR (66-79 beats per
      minute), they were obtained during both ES and ED. Optimal ECG pulsing windows
      for low, intermediate, and high HR were at 60%-76%, 30%-77%, and 31%-47% of the R
      R interval, respectively, and with these levels, the effective dose was decreased
      at low HR from 18.7 to 6.8 mSv, at intermediate HR from 14.7 to 13.4 mSv, and at
      high HR from 11.3 to 4.2 mSv. CONCLUSION: With optimal ECG pulsing, radiation
      exposure to patients, particularly those with low or high HR, can be reduced with
      preservation of image quality.

PMID- 18710976
TI  - Incidence of nephrogenic systemic fibrosis at two large medical centers.
AB  - PURPOSE: To determine the incidence and associated risk factors of nephrogenic
      systemic fibrosis (NSF) in patients who undergo gadolinium-based contrast agent
      (GBCA)-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS:
      Institutional review board approval was obtained for retrospective review of the
      medical records from two hospitals to identify all cases of biopsy-confirmed NSF
      and all patients administered a GBCA from January 1, 1997, to June 30, 2007.
      Informed patient consent was not required. The incidence of NSF was calculated
      for patients who received a standard dose of GBCA, patients who received a high
      dose, and subgroups of patients with renal impairment. RESULTS: Fifteen patients
      developed NSF after gadolinium-enhanced MR imaging. All of them had an estimated
      glomerular filtration rate (eGFR) lower than 30 mL/min, and 11 had acute renal
      failure or acute deterioration of chronic renal failure. The incidence of NSF
      after gadolinium-enhanced MR imaging without screening for renal function was
      zero of 74,124 patients with the standard dose of GBCA and 15 (0.17%) of 8997
      patients with the high dose (P < .001). The NSF incidence associated with a high
      dose of GBCA increased to 0.4% in patients in a chronic hemodialysis program and
      to 8.8% in those who had an eGFR lower than 15 mL/min but were not undergoing
      hemodialysis (P < .001). The NSF incidence in the patients with acute renal
      failure who received a high dose when their creatinine level was increasing was
      19% (11 of 58 patients) when hemodialysis was delayed for longer than 2 days.
      More patients with NSF had proinflammatory events, and compared with patients
      without NSF, these patients had lower pH, younger age, lower eGFR, elevated serum
      phosphorus levels, and a longer delay between GBCA injection and hemodialysis.
      CONCLUSION: For patients with an eGFR lower than 15 mL/min, hemodialysis helped
      to prevent NSF. For patients with an eGFR lower than 30 mL/min who received a
      high dose of GBCA, acute renal failure, delayed hemodialysis after contrast agent
      injection, proinflammatory events, and hyperphosphatemia were associated with
      increased risk of NSF.

PMID- 18710977
TI  - Quality of reporting of diagnostic accuracy studies: no change since STARD
      statement publication--before-and-after study.
AB  - PURPOSE: To determine the quality of reporting of diagnostic accuracy studies
      before and after the Standards for Reporting of Diagnostic Accuracy (STARD)
      statement publication and to determine whether there is a difference in the
      quality of reporting by comparing STARD (endorsing) and non-STARD (nonendorsing)
      journals. MATERIALS AND METHODS: Diagnostic accuracy studies were identified by
      hand searching six STARD and six non-STARD journals for 2001, 2002, 2004, and
      2005. Diagnostic accuracy studies (n = 240) were assessed by using a checklist of
      13 of 25 STARD items. The change in the mean total score on the modified STARD
      checklist was evaluated with analysis of covariance. The change in proportion of
      times that each individual STARD item was reported before and after STARD
      statement publication was evaluated (chi(2) tests for linear trend). RESULTS:
      With mean total score as dependent factor, analysis of covariance showed that the
      interaction between the two independent factors (STARD or non-STARD journal and
      year of publication) was not significant (F = 0.664, df = 3, partial eta(2) =
      0.009, P = .58). Additionally, the frequency with which individual items on the
      STARD checklist were reported before and after STARD statement publication has
      remained relatively constant, with little difference between STARD and non-STARD
      journals. CONCLUSION: After publication of the STARD statement in 2003, the
      quality of reporting of diagnostic accuracy studies remained similar to pre-STARD
      statement publication levels, and there was no meaningful difference (ie, one
      additional item on the checklist of 13 of 25 STARD items being reported) in the
      quality of reporting between those journals that published the STARD statement
      and those that did not.

PMID- 18710979
TI  - DNA double-strand breaks after percutaneous transluminal angioplasty.
AB  - PURPOSE: To determine exemplarily the amount of DNA damage and the repair
      kinetics after interventional radiologic procedures by using visualization of
      foci of the phosphorylated form of the H2AX histone variant (gammaH2AX) to
      quantify DNA double-strand breaks (DSBs) at percutaneous transluminal angioplasty
      (PTA) of the lower limb arteries. MATERIALS AND METHODS: After local ethics
      committee approval and written informed consent were obtained, five patients (two
      women, three men; mean age, 64.4 years; age range, 45-76 years) scheduled for
      computed tomography (CT) and 20 patients (six women, 14 men; mean age, 68.5
      years; age range, 53-85 years) scheduled for PTA of lower limb arteries were
      prospectively entered into the study. Blood samples were taken before the first
      exposure to ionizing radiation and 5 minutes, 1 hour, 6 hours, and 24 hours after
      the last exposure. Additional samples were taken from the irradiated limb
      (femoral vein) of three patients who underwent PTA--before the first radiation
      exposure, 5 and 10 minutes after the first exposure, and 5 minutes after the last
      exposure. Lymphocytes were isolated, fixed, and stained with anti-gammaH2AX
      antibody, and gammaH2AX focus yields were determined with fluorescence
      microscopy. Data were analyzed with linear regression and two-sample F tests.
      RESULTS: Mean increase in number of gammaH2AX foci after CT (7.78 per 1 Gy x cm)
      depended linearly on dose-length product (r = 0.997). Number of foci reached
      background levels within 24 hours. Mean numbers of gammaH2AX foci per cell
      increased by factors of 4.08-20.67 in blood samples taken 5 minutes after PTA
      compared with mean numbers of foci before PTA. Mean radiation dose increase,
      6.56/(10 Gy x cm(2)), depended linearly on dose-area product (r = 0.993). Maximal
      focus yield in cells taken directly from the irradiated limb was higher than that
      in cells from the systemic circulation (by mean factor of 1.46). Data showed
      compromised DSB repair capacity after PTA (P < .05). Mean number of foci at 24
      hours (0.07 focus per cell) was significantly higher than mean number of foci in
      cell background (0.04 focus per cell, P < .05). CONCLUSION: GammaH2AX focus
      formation can be used to determine in vivo induction of DNA DSBs after PTA. DSB
      repair capacity is compromised in patients who undergo PTA of lower limb
      arteries.

PMID- 18710978
TI  - Breast tumor xenografts: diffusion-weighted MR imaging to assess early therapy
      with novel apoptosis-inducing anti-DR5 antibody.
AB  - PURPOSE: To measure the early therapeutic response to a novel apoptosis-inducing
      antibody, TRA-8, by using diffusion-weighted magnetic resonance (MR) imaging in a
      mouse breast cancer model. MATERIALS AND METHODS: Animal experiments had
      institutional animal care and use committee approval. Four groups of nude mice
      bearing luciferase-positive breast tumors (four to five mice with eight to 10
      tumors per group) were injected intravenously with 0 mg (group 1), 0.025 mg
      (group 2), 0.100 mg (group 3), or 0.200 mg (group 4) of TRA-8 on days 0 and 3.
      Diffusion-weighted imaging, anatomic MR imaging, and bioluminescence imaging were
      performed on days 0, 3, and 6 before dosing. Averaged apparent diffusion
      coefficients (ADCs) for both whole tumor volume and a 1-mm peripheral tumor shell
      were calculated and were compared with tumor volume and living tumor cell
      changes. After imaging at day 6, proliferating and apoptotic cell densities were
      measured with Ki67 and terminal deoxynucleotidyl transferase mediated dUTP nick
      end labeling, or TUNEL, staining, respectively, and were compared with cleaved
      caspase-3 density. RESULTS: The ADC increase at day 3 was dependent on TRA-8 dose
      level, averaging 6% +/- 3 (standard error of mean), 19% +/- 4, 14% +/- 4, and 34%
      +/- 7 in the whole tumor volume and 1% +/- 2, 9% +/- 5, 13% +/- 5, and 30% +/- 8
      in the outer 1-mm tumor shell only for groups 1, 2, 3, and 4, respectively. The
      ADC increase in group 4 was significantly higher (P = .0008 and P = .0189 for
      whole tumor volume and peripheral region, respectively) than that in group 1 on
      day 3, whereas tumor size did not significantly differ. At day 3, the dose
      dependent ADC increases were linearly proportional to apoptotic cell and cleaved
      caspase-3 densities and were inversely proportional to the density of cells
      showing Ki67 expression. CONCLUSION: Diffusion-weighted imaging enabled
      measurement of early breast tumor response to TRA-8 treatment, prior to
      detectable tumor shrinkage, providing an effective mechanism to noninvasively
      monitor TRA-8 efficacy. SUPPLEMENTAL MATERIAL:
      http://radiology.rsnajnls.org/cgi/content/full/248/3/844/DC1.

PMID- 18710980
TI  - Virtual dissection CT colonography: evaluation of learning curves and reading
      times with and without computer-aided detection.
AB  - PURPOSE: To prospectively evaluate the learning curves and reading times of
      inexperienced readers who used the virtual dissection reading method for
      retrospective computed tomographic (CT) colonography data sets, with and without
      concurrent computer-aided detection (CAD). MATERIALS AND METHODS: An
      Institutional Review Board approved this study; informed consent was waived. Four
      radiologists without experience in CT colonography evaluated 100 optical
      colonoscopy-proved data sets of 100 patients (49 men, 51 women; mean age, 59
      years +/- 13 [standard deviation]; range, 21-85 years) by using the virtual
      dissection reading method. Two readers used concurrent CAD. Data sets were read
      during five consecutive 1-day sessions (20 data sets per session). Polyp
      detection and false-positive rates, receiver operating characteristics (ROCs),
      and reading times were calculated for individual, CAD group, and non-CAD group
      readings. Diagnostic values were compared by calculating the 95% confidence
      intervals (CIs) around the relative risk. Areas under ROC curves (AUCs) (Hanley
      and McNeil for paired analysis and z statistics for unpaired analysis) and
      reading times (Wilcoxon signed rank test) were compared across the sessions,
      within each session and for the whole study. RESULTS: The range of detection
      rates was 79 of 111 (.71 [95% CI: .61, .79]) to 91 of 111 (.82 [95% CI: .73,
      .88]). The range of false-positive rates was 17 of 111 (.15 [95% CI: .09, .23])
      to 22 of 111 (.20 [95% CI: .12, .28]). All readers' AUCs rose from session 1 to
      session 4; this rise was significant (P < .05) for the non-CAD group. Only during
      session 1 was the CAD group AUC (.83) higher than the non-CAD group AUC (.54) (P
      < .05). Comparison of CAD and non-CAD reading times showed no significant
      difference for the whole study or during each session (P > .05). CONCLUSION: The
      virtual dissection reading technique allows short learning curves, which may be
      improved by the concurrent use of CAD, without significant effect on average
      reading time.

PMID- 18710981
TI  - The role of abdominal radiography in the evaluation of the nontrauma emergency
      patient.
AB  - PURPOSE: To characterize the utility of abdominal radiography for nontrauma
      emergency patients in a single-institution setting. MATERIALS AND METHODS:
      Following approval from the Director of Professional Services, a retrospective
      review of radiography and of patient records was conducted for patients who
      presented to a nontrauma emergency department over a period of 6 months and who
      were imaged by using abdominal radiography. Only the first radiograph per patient
      was used for analysis. The interpretations were sorted as normal, nonspecific, or
      abnormal. The patients' medical records were reviewed to determine whether
      further imaging was performed (computed tomography, ultrasonography, or upper
      gastrointestinal imaging) and results were compared with abdominal radiography.
      Chart reviews were conducted to identify patients in whom abdominal radiography
      alone influenced treatment. RESULTS: In 874 patients, interpretation of abdominal
      radiography was normal in 34% (n = 300), nonspecific in 46% (n = 406), and
      abnormal in 19% (n = 168). Further imaging was performed for 50% (436) of all
      patients. Of 300 patients whose abdominal radiography results were normal, 42% (n
      = 125) had follow-up imaging; 72% (n = 90) of these showed abnormal, 78% (165 of
      212) showed nonspecific, and 87% (86 of 99) showed abnormal findings. Of 438
      patients who did not undergo follow-up imaging, 75% (n = 327) were discharged.
      For all indications other than catheter placement, abdominal radiography helped
      confirm the suspected diagnosis in 2%-8% of cases. In 37 (4%) of 874 patients,
      abdominal radiography was possibly helpful in changing patient treatment without
      a follow-up study. CONCLUSION: Abdominal radiography is often requested; however,
      its results contribute to patient treatment in a small percentage of cases. With
      the exception of catheter placement, if a patient requires investigation beyond
      clinical history, physical examination, and lab results, the emergency physician
      should be encouraged to request more definitive imaging.

PMID- 18710982
TI  - Apparent diffusion coefficient: potential imaging biomarker for prediction and
      early detection of response to chemotherapy in hepatic metastases.
AB  - PURPOSE: To evaluate the ability of the apparent diffusion coefficient (ADC) to
      help predict response to chemotherapy in patients with colorectal and gastric
      hepatic metastases. MATERIALS AND METHODS: Institutional review board approval
      was obtained; all patients provided informed consent. Standard magnetic resonance
      (MR) imaging and diffusion-weighted (DW) MR imaging were performed before and 3,
      7, and 42 days after initiating chemotherapy for 87 hepatic metastases in 23
      colorectal and gastric cancer patients (16 men, seven women; mean age, 55.7
      years; range, 33-71 years). Lesions were classified as either responding or
      nonresponding, according to changes in size at the end of therapy. Linear mixed
      effects modeling was applied to analyze change in ADCs and size following
      treatment. The Pearson correlation test was calculated between those ADC
      parameters and tumor response. RESULTS: Thirty-eight responding and 49
      nonresponding metastatic lesions were evaluated. Pretherapy mean ADCs in
      responding lesions were significantly lower than those of nonresponding lesions
      (P = .003). An early increase in ADCs (on day 3 or 7) was observed in responding
      lesions but not in nonresponding lesions (P = .002). Weak but significant
      correlations were found between final tumor size reduction and both pretreatment
      ADCs (P = .006) and early ADC changes (day 3, P = .004; day 7, P < .001).
      CONCLUSION: ADC seems to be a promising tool for helping predict and monitor the
      early response to chemotherapy of hepatic metastases from colorectal and gastric
      carcinomas.

PMID- 18710983
TI  - Colorectal liver metastases: contrast agent diffusion coefficient for
      quantification of contrast enhancement heterogeneity at MR imaging.
AB  - PURPOSE: To describe and determine the reproducibility of a simplified model to
      quantitatively measure heterogeneous intralesion contrast agent diffusion in
      colorectal liver metastases. MATERIALS AND METHODS: This HIPAA-compliant
      retrospective study received institutional review board approval, and written
      informed consent was obtained from 14 patients (mean age, 61 years +/- 9
      [standard deviation]; range, 41-78 years), including 10 men (mean age, 65 years
      +/- 8; range, 47-78 years) and four women (mean age, 54 years +/- 9; range, 41-59
      years), with colorectal liver metastases. Magnetic resonance (MR) imaging was
      performed twice (first baseline MR image [B(1)] and second baseline MR image
      [B(2)]) in a single target lesion prior to therapy. Dynamic contrast material
      enhanced MR imaging was performed by using a saturation-recovery fast gradient
      echo sequence. A simplified contrast agent diffusion model was proposed, and a
      contrast agent diffusion coefficient (CDC) was calculated. The reproducibility of
      the CDC measurement was evaluated by using the Bland-Altman plot and a linear
      regression model. RESULTS: The mean CDC was 0.22 mm(2)/sec (range, 0.01-0.73
      mm(2)/sec) on B(1) and 0.24 mm(2)/sec (range, 0.01-0.71 mm(2)/sec) on B(2), with
      an intraclass correlation coefficient of 0.91 (P < .0001). Bland-Altman plot
      showed good agreement, with a mean difference in measurement pairs of 0.017
      mm(2)/sec +/- 0.096. The slope from the linear regression model was 0.89 (95%
      confidence interval: 0.63, 1.15) and the intercept was 0.01 (95% confidence
      interval: -0.08, 0.09). CONCLUSION: The CDC enables a quantitative description of
      contrast enhancement heterogeneity in lesions. Given the high reproducibility of
      the CDC metric, CDC appears promising for further qualification as an imaging
      biomarker of change measurement in response assessment. SUPPLEMENTAL MATERIAL:
      http://radiology.rsnajnls.org/cgi/content/full/248/3/901/DC1.

PMID- 18710984
TI  - Semiquantitative assessment of MR imaging in prediction of efficacy of
      gonadotropin-releasing hormone agonist for volume reduction of uterine leiomyoma:
      initial experience.
AB  - PURPOSE: To prospectively determine if semiquantitative assessment of R2* images
      and T1-weighted magnetic resonance (MR) images of leiomyomas correlates with the
      efficacy of gonadotropin-releasing hormone (GnRH) agonist treatment for volume
      reduction. MATERIALS AND METHODS: Internal review board approval and informed
      consent were obtained for this study. Twenty women (mean age, 36.3 years) with
      intramyometrial leiomyomas were enrolled in this study. Single-section double
      echo dynamic MR imaging was performed before GnRH agonist administration. T2
      weighted images were obtained before and after two or three GnRH agonist
      injections (1.88 mg leuprorelin acetate). The steepest signal intensity (SI)
      upslope on T1-weighted images and the area under the curve (AUC) on R2* images
      were determined by using a 16 x 16-voxel matrix that was placed in the center of
      a leiomyoma. Pearson correlation analysis was performed to compare the percentage
      of volume reduction with SI upslope and AUC. Unpaired t test was performed to
      evaluate the difference between leiomyomas with AUC and SI upslope values that
      were less than or greater than the mean. RESULTS: Percentage of volume reduction
      ranged from 6.2% to 51.1%. The mean AUC and mean SI upslope were 39.2 and 9.83%
      per second, respectively. There was a significant correlation between the AUC and
      the percentage of volume reduction (r = 0.81, P < .001), although no significant
      correlation was observed between the SI upslope and the percentage of volume
      reduction. A significant difference in percentage of volume reduction was
      observed in leiomyomas by using mean AUC as a cutoff value (P = .003).
      CONCLUSION: AUC on R2* images correlates with the efficacy of GnRH agonist before
      initiation of treatment for volume reduction of leiomyoma.

PMID- 18710985
TI  - Dual-targeted contrast agent for US assessment of tumor angiogenesis in vivo.
AB  - PURPOSE: To develop and validate a dual-targeted ultrasonographic (US) imaging
      agent with microbubbles (MBs) that attaches to both vascular endothelial growth
      factor (VEGF) receptor 2 (VEGFR2) and alpha(v)beta(3) integrin and to compare the
      US imaging signal obtained from dual-targeted MBs (MB(D)) with that from single
      targeted MBs (MB(S)) in a murine model of tumor angiogenesis. MATERIALS AND
      METHODS: Animal protocols were approved by the institutional Administrative Panel
      on Laboratory Animal Care. Single- and dual-targeted US imaging agents were
      prepared by attaching anti-VEGFR2, anti-alpha(v)beta(3) integrin, or both
      antibodies to the shell of perfluorocarbon-filled MBs. Binding specificities of
      targeted MBs compared with isotype-matched immunoglobulin G-labeled control MBs
      (MB(C)) and nontargeted nonlabeled MBs (MB(N)) were tested with VEGFR2-positive
      and alpha(v)beta(3) integrin-positive cells (mouse SVR cells) and control cells
      (mouse 4T1 cells). In vivo imaging signals of contrast material-enhanced US by
      using anti-VEGFR2-targeted MBs (MB(V)), anti-alpha(v)beta(3) integrin-targeted
      MBs (MB(I)), MB(D), and MB(C) were quantified in 49 mice bearing SK-OV-3 tumors
      (human ovarian cancer). Tumor tissue was stained for VEGFR2, alpha(v)beta(3)
      integrin, and CD31. RESULTS: Attachment of MB(D) to SVR cells (mean, 0.74 MBs per
      cell +/- 0.05 [standard deviation]) was significantly higher than attachment to
      4T1 cells (mean, 0.04 +/- 0.03), and attachment to SVR cells was higher for MB(D)
      than for MB(V) (mean, 0.58 +/- 0.09), MB(I) (mean, 0.42 +/- 0.21), MB(C) (mean,
      0.11 +/- 0.13), and MB(N) (mean, 0.01 +/- 0.01) (P < .05). Imaging signal in the
      murine tumor angiogenesis model was significantly higher (P < .001) for MB(D)
      (mean, 16.7 +/- 7.2) than for MB(V) (mean, 11.3 +/- 5.7), MB(I) (mean, 7.8 +/-
      5.3), MB(C) (mean, 2.8 +/- 0.9), and MB(N) (mean, 1.1 +/- 0.4).
      Immunofluorescence confirmed expression of VEGFR2 and alpha(v)beta(3) integrin on
      tumor vasculature. CONCLUSION: Dual-targeted contrast-enhanced US directed at
      both VEGFR2 and alpha(v)beta(3) integrin improves in vivo visualization of tumor
      angiogenesis in a human ovarian cancer xenograft tumor model in mice.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsnajnls.org/cgi/content/full/248/3/936/DC1.

PMID- 18710986
TI  - Bone and soft-tissue lesions: what factors affect diagnostic yield of image
      guided core-needle biopsy?
AB  - PURPOSE: To assess lesion-related and technical factors that affect diagnostic
      yield in image-guided core-needle biopsy (CNB) of bone and soft-tissue lesions.
      MATERIALS AND METHODS: Institutional review board approval and verbal informed
      consent were obtained for a HIPAA-compliant prospective study of 151 consecutive
      CNBs of bone (n = 88) and soft-tissue (n = 63) lesions. Each CNB specimen was
      reported separately in the final pathology report. Diagnostic yield (total number
      of biopsies that yield a diagnosis divided by total number of biopsies) was
      calculated for all lesions and subgroups on the basis of lesion composition
      (lytic, sclerotic, soft tissue), lesion size (< or = 2, > 2 to 5, or > 5 cm),
      biopsy needle gauge, image guidance modality, number of specimens obtained, and
      specimen length (< 5, 5-10, or > 10 mm). The minimum number of specimens required
      to obtain a diagnosis was determined on the basis of the specimen number at which
      the diagnostic yield reached a plateau. Chi(2) And Wilcoxon rank-sum tests were
      performed in bivariate analyses to evaluate associations between each factor and
      diagnostic yield. Significant factors were evaluated with multivariate logistic
      regression. RESULTS: Diagnostic yield was 77% for all lesions. Yield was 87% for
      lytic bone lesions and 57% for sclerotic bone lesions (P = .002). Diagnostic
      yield increased with larger lesions (54% for lesions < or = 2 cm, 75% for lesions
      > 2 to 5 cm, and 86% for lesions > 5 cm [P = .006]). There was no difference in
      diagnostic yield for bone versus soft-tissue lesions or according to needle gauge
      or image guidance modality. Diagnostic yield was 77% for bone lesions and 76% for
      soft-tissue lesions (P = .88). Yield was 83%, 72%, 77%, and 83% for biopsies
      performed with 14-, 15-, 16-, and 18-gauge needles, respectively (P = .57). Yield
      was 77% with computed tomographic guidance and 78% with ultrasonographic guidance
      (P = .99). Diagnostic yield increased with number of specimens obtained and with
      longer specimen length; it reached a plateau at three specimens for bone lesions
      and four specimens for soft-tissue lesions. CONCLUSION: Diagnostic yield is
      higher in lytic than in sclerotic bone lesions, in larger lesions, and for longer
      specimens. Obtaining a minimum of three specimens in bone lesions and four
      specimens in soft-tissue lesions optimizes diagnostic yield.

PMID- 18710987
TI  - Radiographic evaluation of intussusception: utility of left-side-down decubitus
      view.
AB  - PURPOSE: To assess the incremental value of the left-side-down decubitus view in
      radiographic evaluation of ileocolic intussusception. MATERIALS AND METHODS: The
      institutional review board approved this retrospective investigation with waiver
      of informed consent. Between February 24, 2002, and January 25, 2007, 304 studies
      (300 patients; mean age, 1.3 years; range, 0.1-3.9 years) met the following
      inclusion criteria: kidney ureter bladder (KUB) and decubitus views obtained,
      with subsequent proof of diagnosis. Using a consensus approach, two pediatric
      radiologists evaluated KUB and decubitus views for four variables: (a) discrete
      mass and (b) small-bowel obstruction (positive criteria); (c) air or stool in
      ascending colon and (d) cecal air or stool (negative criteria). On the basis of
      these criteria, each study was graded as negative, positive, or indeterminate for
      intussusception. Diagnostically determinate studies and the ability to visualize
      or exclude intussusception were calculated to determine sensitivity and
      specificity. The difference between proportions was calculated, along with 95%
      confidence intervals. Agreement between the supine KUB view and supine KUB plus
      left-side-down decubitus views was tested with the McNemar test. RESULTS:
      Intussusception was present in 58 of 304 studies (19%). Adding the decubitus view
      to the KUB view increased the number of determinate studies from 110 of 304
      (36.2%) to 205 of 304 (67.4%) (difference, 31.2 percentage points; P < .001).
      Intussusception was correctly identified with KUB view alone in 35 of 58 studies
      (60.3%); this value increased to 43 of 58 (74.1%) with KUB plus decubitus views
      (P = .0215). Intussusception was correctly excluded with the KUB view alone in 63
      of 246 studies (25.6%); this increased to 143 of 246 studies (58.1%) with
      addition of the decubitus view (P < .0001). CONCLUSION: The addition of decubitus
      views increased the number of diagnostically determinate studies and increased
      the ability to diagnose or exclude intussusception. The authors believe that a
      left-side-down decubitus view should be included in the initial evaluation of
      patients suspected of having intussusception, particularly when the supine view
      is diagnostically indeterminate.

PMID- 18710988
TI  - Converting dose-length product to effective dose at CT.
AB  - PURPOSE: To determine effective dose (ED) per unit dose-length product (DLP)
      conversion factors for computed tomographic (CT) dosimetry. MATERIALS AND
      METHODS: A CT dosimetry spreadsheet was used to compute patient ED values and
      corresponding DLP values. The ratio of ED to DLP was determined with 16-section
      CT scanners from four vendors, as well as with five models from one manufacturer
      that spanned more than 25 years. ED-to-DLP ratios were determined for 2-cm scan
      lengths along the patient axis, as well as for typical scan lengths encountered
      at head and body CT examinations. The dependence of the ratio of ED to DLP on x
      ray tube voltage (in kilovolts) was investigated, and the values obtained with
      the spreadsheet were compared with those obtained by using two other commercially
      available CT dosimetry software packages. RESULTS: For 2-cm scan lengths, changes
      in the scan region resulted in differences to ED of a factor of 30, but much
      lower variation was obtained for typical scan lengths at clinical head and body
      imaging. Inter- and intramanufacturer differences for ED/DLP were generally
      small. Representative values of ED/DLP at 120 kV were 2.2 microSv/mGy x cm (head
      scans), 5.4 microSv/mGy x cm (cervical spine scans), and 18 microSv/mGy x cm
      (body scans). For head scans, ED/DLP was approximately independent of x-ray tube
      voltage, but for body scans, the increase from 80 to 140 kV increased the ratio
      of ED to DLP by approximately 25%. Agreement in ED/DLP data for all three
      software packages was generally very good, except for cervical spine examinations
      where one software package determined an ED/DLP ratio that was approximately
      double that of the other two. CONCLUSION: This article describes a method of
      providing CT users with a practical and reliable estimate of adult patient EDs by
      using the DLP displayed on the CT console at the end of any given examination.

PMID- 18710989
TI  - Left ventricle: automated segmentation by using myocardial effusion threshold
      reduction and intravoxel computation at MR imaging.
AB  - This retrospective analysis of existing patient data had institutional review
      board approval and was performed in compliance with HIPAA. No informed consent
      was required. The purpose of the study was to develop and validate an algorithm
      for automated segmentation of the left ventricular (LV) cavity that accounts for
      papillary and/or trabecular muscles and partial voxels in cine magnetic resonance
      (MR) images, an algorithm called LV Myocardial Effusion Threshold Reduction with
      Intravoxel Computation (LV-METRIC). The algorithm was validated in biologic
      phantoms, and its results were compared with those of manual tracing, as well as
      those of a commercial automated segmentation software (MASS [MR Analytical
      Software System]), in 38 subjects. LV-METRIC accuracy in vitro was 98.7%. Among
      the 38 subjects studied, LV-METRIC and MASS ejection fraction estimations were
      highly correlated with manual tracing (R(2) = 0.97 and R(2) = 0.95,
      respectively). Ventricular volume estimations were smaller with LV-METRIC and
      larger with MASS than those calculated by using manual tracing, though all
      results were well correlated (R(2) = 0.99). LV-METRIC volume measurements without
      partial voxel interpolation were statistically equivalent to manual tracing
      results (P > .05). LV-METRIC had reduced intraobserver and interobserver
      variability compared with other methods. MASS required additional manual
      intervention in 58% of cases, whereas LV-METRIC required no additional
      corrections. LV-METRIC reliably and reproducibly measured LV volumes.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsnajnls.org/cgi/content/full/248/3/1004/DC1.

PMID- 18710991
TI  - Simultaneous MR/PET imaging of the human brain: feasibility study.
AB  - The purpose of this study was to apply a magnetic resonance (MR) imaging
      compatible positron emission tomographic (PET) detector technology for
      simultaneous MR/PET imaging of the human brain and skull base. The PET detector
      ring consists of lutetium oxyorthosilicate (LSO) scintillation crystals in
      combination with avalanche photodiodes (APDs) mounted in a clinical 3-T MR imager
      with use of the birdcage transmit/receive head coil. Following phantom studies,
      two patients were simultaneously examined by using fluorine 18 fluorodeoxyglucose
      (FDG) PET and MR imaging and spectroscopy. MR/PET data enabled accurate
      coregistration of morphologic and multifunctional information. Simultaneous
      MR/PET imaging is feasible in humans, opening up new possibilities for the
      emerging field of molecular imaging.

PMID- 18710990
TI  - Volume rendering with color coding of tagged stool during endoluminal fly-through
      CT colonography: effect on reading efficiency.
AB  - Institutional review board approval and informed consent were obtained. This
      study was conducted to evaluate a newly developed technique for discriminative
      color coding of tagged stool during three-dimensional (3D) endoluminal fly
      through computed tomographic (CT) colonography and to determine its effect on
      reading efficiency. Thirty patients, including three dropouts, were prepared with
      moderate cathartic preparation (20 mg bisacodyl, three doses of 200 mL of 5%
      wt/vol barium sulfate). Images were reviewed by two independent readers with and
      without color coding. Reader preference, interpretation time, and diagnostic
      performance were evaluated. Both reviewers preferred color coding. With color
      coding, interpretation time was shortened by 3 minutes (reader 1, P = .002) and
      2.5 minutes (reader 2, P = .009); sensitivity for 6-mm-diameter or larger lesions
      remained constant at 96% (24 of 25; 95% confidence interval: 78.9%, <100%; P =
      >.99). This technique facilitates primary 3D interpretation of images obtained
      with moderate cathartic preparation.

PMID- 18710992
TI  - Pulmonary emphysema: size distribution of emphysematous spaces on multidetector
      CT images--comparison with macroscopic and microscopic morphometry.
AB  - PURPOSE: To test the hypothesis that the frequency-size distribution of low
      attenuation areas could be a parameter to quantify pulmonary emphysema. MATERIALS
      AND METHODS: Ethics committee approval and written informed consent were
      obtained. Multidetector computed tomographic (CT) scans were performed with
      simultaneous acquisition of four 1-mm sections of the whole chest in 80 patients
      (57 men, 23 women; age range, 38-79 years) who were referred for surgical
      resection of lung cancer. From the raw data, 1.25-mm-thick sections were
      reconstructed at 10-mm intervals. The relative area of lung with attenuation
      coefficients lower than -960 HU (RA(960)) and the 1st percentile of the
      distribution of attenuation coefficients were calculated. The cumulative
      frequency-size distributions of the RA(960) and the 1st percentile, when
      represented on a log-log plot, followed linear relationships. The slopes of these
      lines (D(960) and D(p1)) were compared with areas found macroscopically to have
      emphysema and with two different microscopic measurements assessed on resected
      specimens. Spearman correlation coefficients of each CT index with macroscopic
      and microscopic measurements were calculated. RESULTS: The RA(960) and the 1st
      percentile showed statistically significant correlations with macroscopic and
      microscopic indexes (P < .001), whereas D(960) and D(p1) did not (P > or = .165).
      CONCLUSION: The RA(960) and the 1st percentile reflect the extent of emphysema as
      compared to macroscopic and microscopic measurements, while D(960) and D(p1) do
      not.

PMID- 18710993
TI  - Airway dimensions at inspiratory and expiratory multisection CT in chronic
      obstructive pulmonary disease: correlation with airflow limitation.
AB  - PURPOSE: To analyze the relationship between airflow limitation and airway
      dimensions from the third to the fifth generation of bronchi in patients with
      chronic obstructive pulmonary disease (COPD) by using inspiratory and expiratory
      multisection computed tomography (CT). MATERIALS AND METHODS: This retrospective
      study was approved by the institutional review board, which waived the need for
      informed consent. The study included 50 patients with COPD who underwent both
      inspiratory and expiratory 64-detector CT. In each patient, mean values of airway
      luminal areas from the third to the fifth generation of three bronchi (right B1,
      right B10, and left B3) were measured at inspiratory CT (IA3, IA4, and IA5) and
      expiratory CT (EA3, EA4, and EA5). To evaluate the change of the airway luminal
      area between inspiration and expiration, the ratio of expiratory to inspiratory
      airway luminal area in each generation was calculated (EA3/IA3, EA4/IA4, and
      EA5/IA5). Correlations between airway dimensions and pulmonary function test
      results were evaluated. RESULTS: The correlation coefficients between airway
      luminal area measured at expiratory CT and the forced expiratory volume in 1
      second (FEV(1)) were higher than those for inspiratory CT and improved as the
      airway size decreased from the third to the fifth generation (IA3, r = .02; IA4,
      r = .18; IA5, r = .26; EA3, r = .09; EA4, r = .40; EA5, r = .63). EA5/IA5 had the
      highest correlations with FEV(1) (r = .72, P < .001). There were no significant
      correlations between EA3/IA3 and pulmonary function test results. CONCLUSION:
      Airway lumen measured at expiratory CT was more closely related to expiratory
      airflow measurements than was lumen measured at inspiratory CT. In addition, the
      changes of airway luminal area between inspiration and expiration were strongly
      related to airflow limitation.

PMID- 18710994
TI  - Increasing carotid plaque echolucency is predictive of cardiovascular events in
      high-risk patients.
AB  - PURPOSE: Carotid plaque echolucency seen at ultrasonography (US) is a potential
      indicator of plaque instability and may help identify patients at risk for major
      adverse cardiovascular events (MACEs). The authors performed this study to
      determine whether decreasing gray-scale median (GSM) levels at repeat carotid US
      examinations are associated with future MACEs. MATERIALS AND METHODS: The study
      was approved by the institutional ethics committee and all patients provided
      informed consent. The authors prospectively studied 574 patients with carotid
      plaques of at least 30% from a group of 1268 consecutive patients who were
      initially asymptomatic with respect to carotid disease. GSM levels were
      determined with carotid US at baseline and after a median of 7.5 months (range, 6
      9 months), and the mean change of the GSM was calculated. Patients were then
      followed up clinically for a median of 3.2 years for the occurrence of composite
      MACE. RESULTS: During the initial period, the median change in carotid GSM was
      2.9 (interquartile range [IQR], -6.9 to 11.0). Of 574 study participants, 230
      (40%) showed a reduction of GSM levels and 344 (60%) showed an increase. MACEs
      were observed in 177 (31%) of the 574 patients. Adjusted hazard ratios for the
      lowest quartile (GSM change less than -6.9), the second quartile (GSM change
      between -6.9 and 2.9), and the third quartile (GSM change between 3.0 and 11.0)
      were 1.71 (95% confidence interval [CI]: 1.09, 2.66), 1.36 (95% CI: 0.86, 2.16),
      and 1.22 (95% CI: 0.77, 1.95), respectively, compared with the highest quartile
      (GSM change greater than 11.0) (P = .018). CONCLUSION: Increasing echolucency of
      carotid artery plaques within a 6- to 9-month interval is predictive of midterm
      clinical adverse events of atherosclerosis.

PMID- 18710995
TI  - Visceral and soft-tissue tumors: radiofrequency and alcohol ablation for pain
      relief--initial experience.
AB  - PURPOSE: To determine retrospectively the effectiveness of percutaneous
      radiofrequency ablation (RFA) alone, alcohol ablation alone, or combined RFA and
      alcohol ablation (hereafter, combined ablation) to treat pain in patients with
      visceral and soft-tissue malignancies. MATERIALS AND METHODS: This HIPAA
      compliant study was institutional review board approved; the informed consent
      requirement was waived. Twenty patients, with 28 tumors, who underwent
      percutaneous computed tomography (CT) or magnetic resonance (MR)-guided RFA
      and/or alcohol ablation for pain relief over a 2-year period were retrospectively
      identified, and their medical and imaging data were studied: Nineteen patients
      were referred for ablation because of persistent pain despite use of analgesics,
      and one patient had refused analgesics. The 28 tumors were located in the liver,
      lung, adrenal gland, retroperitoneum, gluteal muscle, inguinal mass, and
      subcutaneous tissues on the back. Fifteen tumors were treated with RFA alone, 12
      were treated with combined ablation (when lesions were > 4 cm in diameter, except
      in lung or renal tumors), and one was treated with alcohol ablation alone. Pain
      was quantified on a 0-10 scale before, 1 day after, and 1-6 weeks after ablation.
      On the basis of changes in pain score and pain medication use, pain was reported
      with a composite measure as complete, partial, or no pain response. Quantitative
      pain scale values were compared by using Friedman and Tukey post hoc tests to
      assess significant changes. RESULTS: At 1-6-week follow-up, pain relief was
      complete in nine patients (45%) and partial in six (30%); pain relief did not
      occur in five patients (25%). There was a significant (P < .05) decrease in pain
      at 1-day and 1-6-week follow-up compared with pain at baseline. Three adverse
      events were caused by therapy: Two were major complications (femoral neuropathy
      in one patient, perinephric hematoma and hemobilia in one patient), and one was a
      side effect of ablation (right shoulder pain) that resolved spontaneously.
      CONCLUSION: Percutaneous RFA alone or in combination with alcohol ablation
      provided pain relief from visceral tumors in most patients with intractable pain.

PMID- 18710997
TI  - Case 137: Pneumonia and bronchiectasis secondary to unrecognized peanut
      impaction.

PMID- 18710998
TI  - Fleischner Society glossary of terms: infiltrates.

PMID- 18710999
TI  - Mammographically determined breast density and cancer risk.

PMID- 18711000
TI  - A prospective study of mitochondrial DNA copy number and risk of non-Hodgkin
      lymphoma.
AB  - Mitochondrial DNA (mtDNA) copy number is increased in patients with chronic
      lymphocytic leukemia (CLL), in Burkitt lymphoma and Epstein-Barr virus
      transformed lymphoblastoid cell lines, and in T cells activated via the T-cell
      receptor. We hypothesized that having a higher mtDNA copy number in peripheral
      white blood cell DNA from healthy subjects would be associated with future risk
      of non-Hodgkin lymphoma (NHL). We analyzed mtDNA copy number in 104 incident male
      NHL cases and 104 matched controls within the prospective Alpha-Tocopherol, Beta
      Carotene (ATBC) Cancer Prevention cohort. There was a dose-response relationship
      between tertiles of mtDNA copy number and risk of NHL (odds ratio [OR], 95%
      confidence interval [CI]: 1.0; 1.4 [0.7-2.8]; and 2.4 [1.0-5.5], respectively;
      P(trend) = .046). The effect was most pronounced for the CLL/small lymphocytic
      lymphoma (SLL) subtype (OR: 1.0; 3.2 [0.7-15.7]; 14.1 [1.9-103.2]; P(trend) =
      .009). These results suggest that mtDNA copy number could be associated with the
      risk of NHL, particularly CLL/SLL.

PMID- 18711001
TI  - Fc gamma R-stimulated activation of the NADPH oxidase: phosphoinositide-binding
      protein p40phox regulates NADPH oxidase activity after enzyme assembly on the
      phagosome.
AB  - The phagocyte NADPH oxidase generates superoxide for microbial killing, and
      includes a membrane-bound flavocytochrome b(558) and cytosolic p67(phox),
      p47(phox), and p40(phox) subunits that undergo membrane translocation upon
      cellular activation. The function of p40(phox), which binds p67(phox) in resting
      cells, is incompletely understood. Recent studies showed that phagocytosis
      induced superoxide production is stimulated by p40(phox) and its binding to
      phosphatidylinositol-3-phosphate (PI3P), a phosphoinositide enriched in membranes
      of internalized phagosomes. To better define the role of p40(phox) in FcgammaR
      induced oxidase activation, we used immunofluorescence and real-time imaging of
      FcgammaR-induced phagocytosis. YFP-tagged p67(phox) and p40(phox) translocated to
      granulocyte phagosomes before phagosome internalization and accumulation of a
      probe for PI3P. p67(phox) and p47(phox) accumulation on nascent and internalized
      phagosomes did not require p40(phox) or PI3 kinase activity, although superoxide
      production before and after phagosome sealing was decreased by mutation of the
      p40(phox) PI3P-binding domain or wortmannin. Translocation of p40(phox) to
      nascent phagosomes required binding to p67(phox) but not PI3P, although the loss
      of PI3P binding reduced p40(phox) retention after phagosome internalization. We
      conclude that p40(phox) functions primarily to regulate FcgammaR-induced NADPH
      oxidase activity rather than assembly, and stimulates superoxide production via a
      PI3P signal that increases after phagosome internalization.

PMID- 18711002
TI  - Lectin-like domain of thrombomodulin binds to its specific ligand Lewis Y antigen
      and neutralizes lipopolysaccharide-induced inflammatory response.
AB  - Thrombomodulin (TM), a widely expressing glycoprotein originally identified in
      vascular endothelium, is an important cofactor in the protein C anticoagulant
      system. TM appears to exhibit anti-inflammatory ability through both protein C
      dependent and -independent pathways. We presently have demonstrated that
      recombinant N-terminal lectinlike domain of TM (rTMD1) functions as a protective
      agent against sepsis caused by Gram-negative bacterial infections. rTMD1 caused
      agglutination of Escherichia coli and Klebsiella pneumoniae and enhanced the
      macrophage phagocytosis of these Gram-negative bacteria. Moreover, rTMD1 bound to
      the Klebsiella pneumoniae and lipopolysaccharide (LPS) by specifically
      interacting with Lewis Y antigen. rTMD1 inhibited LPS-induced inflammatory
      mediator production via interference with CD14 and LPS binding. Furthermore,
      rTMD1 modulated LPS-induced mitogen-activated protein kinase and nuclear factor
      kappaB signaling pathway activations and inducible nitric oxide synthase
      expression in macrophages. Administration of rTMD1 protected the host by
      suppressing inflammatory responses induced by LPS and Gram-negative bacteria, and
      enhanced LPS and bacterial clearance in sepsis. Thus, rTMD1 can be used to defend
      against bacterial infection and inhibit LPS-induced inflammatory responses,
      suggesting that rTMD1 may be valuable in the treatment of severe inflammation in
      sepsis, especially in Gram-negative bacterial infections.

PMID- 18711003
TI  - Angiogenesis alteration by defibrotide: implications for its mechanism of action
      in severe hepatic veno-occlusive disease.
AB  - Defibrotide (DF) is a mixture of porcine-derived single-stranded phosphodiester
      oligonucleotides (9-80-mer; average, 50-mer) that has been successfully used to
      treat severe hepatic veno-occlusive disease (sVOD) with multiorgan failure (MOF)
      in patients who have received cytotoxic chemotherapy in preparation for bone
      marrow transplantation. However, its mechanism of action is unknown. Herein, we
      show that DF and phosphodiester oligonucleotides can bind to heparin-binding
      proteins (eg, basic fibroblast growth factor [bFGF] but not vascular endothelial
      growth factor [VEGF] 165) with low nanomolar affinity. This binding occurred in a
      length- and concentration-dependent manner. DF can mobilize proangiogenic factors
      such as bFGF from their depot or storage sites on bovine corneal endothelial
      matrix. However, these molecules do not interfere with high-affinity binding of
      bFGF to FGFR1 IIIc but can replace heparin as a required cofactor for binding and
      hence cellular mitogenesis. DF also protects bFGF against digestion by trypsin
      and chymotrypsin and from air oxidation. In addition, DF binds to collagen I with
      low nanomolar affinity and can promote human microvascular endothelial cell-1
      (HMEC-1) cell mitogenesis and tubular morphogenesis in three-dimensional collagen
      I gels. Thus, our data suggest that DF may provide a stimulus to the sinusoidal
      endothelium of a liver that has suffered a severe angiotoxic event, thus helping
      to ameliorate the clinical sVOD/MOF syndrome.

PMID- 18711004
TI  - Long-term survival of transplanted stem cells in immunocompetent mice with
      muscular dystrophy.
AB  - Satellite cells refer to resident stem cells in muscle that are activated in
      response to damage or disease for the regeneration and repair of muscle fibers.
      The use of stem cell transplantation to treat muscular diseases has been limited
      by impaired donor cell survival attributed to rejection and an unavailable stem
      cell niche. We isolated a population of adult muscle mononuclear cells (AMMCs)
      from normal, strain-matched muscle and transplanted these cells into delta
      sarcoglycan-null dystrophic mice. Distinct from other transplant studies, the
      recipient mice were immunocompetent with an intact endogenous satellite cell
      pool. We found that AMMCs were 35 times more efficient at restoring sarcoglycan
      compared with cultured myoblasts. Unlike cultured myoblasts, AMMC-derived muscle
      fibers expressed sarcoglycan protein throughout their entire length, consistent
      with enhanced migratory ability. We examined the capacity of single injections of
      AMMCs to provide long-term benefit for muscular dystrophy and found persistent
      regeneration after 6 months, consistent with augmentation of the endogenous stem
      cell pool. Interestingly, AMMCs were more effectively engrafted into aged
      dystrophic mice for the regeneration of large clusters of sarcoglycan-positive
      muscle fibers, which were protected from damage, suggesting that the stem cell
      niche in older muscle remains permissive.

PMID- 18711006
TI  - Promoting regulatory gene variation in sodium reabsorption.

PMID- 18711007
TI  - Why can't a woman be more like a man?: Is the angiotensin type 2 receptor to
      blame or to thank?

PMID- 18711008
TI  - Characterization and functional analyses of the human G protein-coupled receptor
      kinase 4 gene promoter.
AB  - The G protein-coupled receptor kinase 4 is involved in renal sodium handling and
      blood pressure regulation. Missense variants have already been tested
      functionally and are associated with hypertension, but no data on promoter
      analyses are yet available. We scanned 94 hypertensive white subjects for genetic
      variation and performed promoter reporter gene analyses in HEK293T, COS7, and
      SaOs-2 cells. Transient transfections with various full lengths and wild-type
      deletion constructs revealed that 1851 bp of the flanking region and 275 bp of
      the 5'-untranslated region were sufficient for transcriptional activities and
      composed a powerful cis-active element in the distal 293 bp. The -1702T and +2T
      alleles resulted in drastic general reductions of promoter function, whereas an
      activity increasing effect of +268C was cell type specific. Electrophoretic
      mobility-shift assay, supershift, and cotransfection analyses of transcription
      factor binding sites predicted in silico (Alibaba2.1/Transfac7) resulted in
      allele-specific binding patterns of nuclear proteins and identified the
      participation of CCAAT/enhancer-binding protein transcription factor family
      members. The G protein-coupled receptor kinase 4 core promoter resides in the
      first 1851 bp upstream of its transcription start site. The 4 identified genetic
      variants within this region exert allele-specific impact on both cell type- and
      stimulation-dependent transcription and may affect the expression balance of
      renal G protein-coupled receptor kinase 4.

PMID- 18711009
TI  - Role of the multidomain protein spinophilin in blood pressure and cardiac
      function regulation.
AB  - Spinophilin controls intensity/duration of G protein-coupled receptor signaling
      and thereby influences synaptic activity. We hypothesize that spinophilin affects
      blood pressure through central mechanisms. We measured blood pressure and heart
      rate in SPL-deficient (SPL(-/-)), heterozygous SPL-deficient (SPL(+/-)), and wild
      type (SPL(+/+)) mice by telemetry combined with fast Fourier transformation. We
      also assessed peripheral vascular reactivity and performed echocardiography. SPL(
      /-) had higher mean arterial pressure than SPL(+/-) and SPL(+/+) (121+/-2, 112+/
      1, and 113+/-1 mm Hg). Heart rate was inversely related to spinophilin expression
      (SPL(-/-) 565+/-0.4, SPL(+/-) 541+/-5, SPL(+/+) 525+/-8 bpm). The blood pressure
      response to prazosin, trimethapane, and the heart rate response to metoprolol
      were stronger in SPL(-/-) than SPL(+/+) mice, whereas heart rate response to
      atropine was attenuated in SPL(-/-). Mesenteric artery vasoreactivity after
      angiotensin II, phenylephrine, and the thromboxane mimetic (U46619) as well as
      change in heart rate, stroke volume, and cardiac output after dobutamine were
      similar in SPL(-/-) and SPL(+/+). Baroreflex sensitivity was attenuated in SPL(-/
      ) compared with SPL(+/-) and SPL(+/+), which was confirmed by pharmacological
      testing. Heart rate variability parameters were attenuated in SPL(-/-) mice. We
      suggest that an increase in central sympathetic outflow participates in blood
      pressure and heart rate increases in SPL(-/-) mice. The elevated blood pressure
      in SPL(-/-) mice was associated with attenuated baroreflex sensitivity and
      decreased parasympathetic activity. Our study is the first to show a role for the
      spinophilin gene in blood pressure regulation.

PMID- 18711010
TI  - Enhanced angiotensin II type 2 receptor mechanisms mediate decreases in arterial
      pressure attributable to chronic low-dose angiotensin II in female rats.
AB  - The renin-angiotensin system is a far more complex enzymatic cascade than
      realized previously. Mounting evidence suggests sex-specific differences in the
      regulation of the renin-angiotensin system and arterial pressure. We examined the
      hemodynamic responses, angiotensin II receptor subtypes, and angiotensin
      converting enzyme 2 gene expression levels after graded doses of angiotensin II
      in males and females. Mean arterial pressure was measured via telemetry in male
      and female rats in response to a 2-week infusion of vehicle, low-dose (50 ng/kg
      per minute SC) or high-dose (400 ng/kg per minute SC) angiotensin II. The effect
      of concurrent infusion of the angiotensin II type 2 receptor (AT(2)R) blocker
      (PD123319) was also examined. The arterial pressure response to high-dose
      angiotensin II was attenuated in females compared with males (24+/-8 mm Hg versus
      42+/-5 mm Hg; P for the interaction between sex and treatment <0.002).
      Remarkably, low-dose angiotensin II decreased arterial pressure (11+/-4 mm Hg; P
      for the interaction between sex and treatment <0.02) at a dose that did not have
      an effect in males. This decrease in arterial pressure in females was abolished
      by AT(2)R blockade. Renal AT(2)R, angiotensin-converting enzyme 2, and left
      ventricular AT(2)R mRNA gene expressions were markedly greater in females than in
      males with a renal angiotensin II type 1a receptor:AT(2)R ratio of approximately
      1 in females. Angiotensin II infusion did not affect renal AT(2)R mRNA expression
      but resulted in significantly less left ventricular mRNA expression. Renal
      angiotensin-converting enzyme 2 mRNA expression levels were greater in females
      than in males treated with high-dose angiotensin II (approximately 2.5 fold; P
      for the interaction between sex and treatment <0.05). In females, enhancement of
      the vasodilatory arm of the renin-angiotensin system, in particular, AT(2)R and
      angiotensin-converting enzyme 2 mRNA expression, may contribute to the sex
      specific differences in response to renin-angiotensin system activation.

PMID- 18711011
TI  - Epithelial sodium channel: mendelian versus essential hypertension.

PMID- 18711012
TI  - Fasting compared with nonfasting lipids and apolipoproteins for predicting
      incident cardiovascular events.
AB  - BACKGROUND: Although guidelines recommend measuring fasting lipids for initial
      screening of adults without cardiovascular disease (CVD), recent studies suggest
      that nonfasting triglycerides may be superior to fasting. Whether fasting status
      alters associations of nontriglyceride lipids with CVD is unclear. METHODS AND
      RESULTS: In a prospective study of 26 330 healthy women (19 983 fasting; 6347
      nonfasting), associations of baseline lipids with incident CVD (754 fasting; 207
      nonfasting) were examined over an 11-year follow-up. Except for triglycerides,
      lipid concentrations differed minimally (<5%) for fasting versus nonfasting.
      However, stronger associations with CVD were noted for fasting total cholesterol
      (adjusted fasting hazard ratio [HR], 1.22 per 1-SD increment; 95% CI, 1.14 to
      1.30; nonfasting HR, 1.07; 95% CI, 0.93 to 1.21), low-density lipoprotein (LDL)
      cholesterol (fasting HR, 1.21; 95% CI, 1.13 to 1.29; nonfasting HR, 1.00; 95% CI,
      0.87 to 1.15), apolipoprotein B-100 (fasting HR, 1.36; 95% CI, 1.27 to 1.45;
      nonfasting HR, 1.20; 95% CI, 1.05 to 1.36), non-high-density lipoprotein (HDL)
      cholesterol (fasting HR, 1.29; 95% CI, 1.21 to 1.38; nonfasting HR, 1.15; 95% CI,
      1.01 to 1.31), and apolipoprotein B-100/A-1 ratio (fasting HR, 1.39; 95% CI, 1.30
      to 1.48; nonfasting HR, 1.18; 95% CI, 1.09 to 1.27). Compared with fasting
      levels, nonfasting HDL cholesterol, apolipoprotein A-1, and total/HDL cholesterol
      ratio had similar associations, and triglycerides had a stronger association,
      with CVD. Significant interactions were seen for LDL cholesterol and
      apolipoprotein B-100/A-1 ratio with fasting status (P for interaction=0.03 and
      <0.001, respectively). CONCLUSIONS: This study demonstrates that HDL cholesterol,
      triglycerides, total/HDL cholesterol ratio, and apolipoprotein A-1 predict CVD
      when measured nonfasting. By contrast, total, LDL, and non-HDL cholesterol, in
      addition to apolipoprotein B-100 and B-100/A-1 ratio, provide less useful CVD
      risk information when nonfasting, despite small changes in their concentrations.
      Guidelines for lipid screening may need to consider these differences.

PMID- 18711013
TI  - Advanced glycation end products accumulate in vascular smooth muscle and modify
      vascular but not ventricular properties in elderly hypertensive canines.
AB  - BACKGROUND: Advanced glycation end products (AGEs) are believed to increase left
      ventricular (LV) and vascular stiffness, in part via cross-linking proteins. We
      determined whether and where AGEs were increased in elderly hypertensive
      nondiabetic dogs and whether an AGE cross-link breaker (ALT-711) improved
      vascular or ventricular function. METHODS AND RESULTS: Elderly dogs with
      experimental hypertension (old hypertensives [OH]) were randomized to receive ALT
      711 (OH+ALT group; n=11; 1 mg/kg PO) or not (OH group; n=11) for 8 weeks.
      Conscious blood pressure measurements (weekly), echocardiography (week 8), and
      anesthetized study (week 8) with LV pressure-volume analysis and aortic pressure
      dimension and pressure-flow assessment over a range of preloads and afterloads
      were performed. In LV and aorta from OH, OH+ALT, and young normal dogs, AGE
      content (immunohistochemistry and Western analysis for N(epsilon)
      (carboxymethyl)lysine [CML]) was assessed. Aortic CML content was markedly
      increased in OH and OH+ALT dogs compared with young normal dogs. CML was
      localized to aortic and aortic vasa vasorum smooth muscle but not to collagen or
      elastin. CML was essentially undetectable in young normal, OH, or OH+ALT
      myocardium but was visible in large vessels in the LV. ALT-711 therapy was
      associated with lower blood pressure and pulse pressure, decreased systemic
      vascular resistance, increased aortic distensibility and arterial compliance,
      and, notably, significant aortic dilatation. Neither LV systolic nor diastolic
      function was different in OH+ALT versus OH dogs. CONCLUSIONS: In elderly
      hypertensive canines, AGE accumulation and AGE cross-link breaker effects were
      confined to the vasculature without evidence of myocardial accumulation or
      effects. The lack of AGE accumulation in collagen-rich areas suggests that the
      striking vascular effects may be mediated by mechanisms other than collagen cross
      linking.

PMID- 18711014
TI  - Peroxisome proliferator-activated receptor-delta agonist enhances vasculogenesis
      by regulating endothelial progenitor cells through genomic and nongenomic
      activations of the phosphatidylinositol 3-kinase/Akt pathway.
AB  - BACKGROUND: Despite the therapeutic potential of endothelial progenitor cells
      (EPCs) in ischemic vascular diseases, their insufficient numbers limit clinical
      applications. Peroxisome proliferator-activated receptor (PPAR)-delta belongs to
      the nuclear hormone receptor superfamily, and its functions in various tissues
      and cells are almost unexplored, especially with respect to vascular biology.
      METHODS AND RESULTS: PPAR-delta activation in EPCs phosphorylated Akt, and this
      phosphorylation was mediated not only by genomic but also by nongenomic pathways
      through interaction with the regulatory subunit of phosphatidylinositol 3-kinase.
      PPAR-delta activation with agonist (GW501516 or L-165041) increased the
      proliferation of human EPCs and protected them from hypoxia-induced apoptosis. In
      addition, PPAR-delta activation enhanced EPC functions, such as transendothelial
      migration, and tube formation. These actions by PPAR-delta activation in EPCs
      were dependent on the phosphatidylinositol 3-kinase/Akt pathway. In ischemic
      hindlimb of mice models, transplantation of PPAR-delta agonist-treated human or
      mouse EPCs enhanced blood flow recovery to ischemic limbs compared with vehicle
      treated EPCs. In EPCs from PPAR-delta-knockout mice, however, treatment with PPAR
      delta agonist did not enhance in vivo vasculogenic potential. Systemic
      administration of PPAR-delta agonist increased hematopoietic stem cells in bone
      marrow and EPCs in peripheral blood, leading to improved vasculogenesis with
      incorporation of bone marrow-derived cells to new vessels in a corneal
      neovascularization model and limb salvage with better blood flow in an ischemic
      hindlimb model. CONCLUSIONS: The results of our study suggest that PPAR-delta
      agonist has therapeutic vasculogenic potential for the treatment of ischemic
      cardiovascular diseases.

PMID- 18711015
TI  - Sleep quality and elevated blood pressure in adolescents.
AB  - BACKGROUND: We assessed whether insufficient sleep is associated with
      prehypertension in healthy adolescents. METHODS AND RESULTS: We undertook a cross
      sectional analysis of 238 adolescents, all without sleep apnea or severe
      comorbidities. Participants underwent multiple-day wrist actigraphy at home to
      provide objective estimates of sleep patterns. In a clinical research facility,
      overnight polysomnography, anthropometry, and 9 blood pressure measurements over
      2 days were made. Exposures were actigraphy-defined low weekday sleep efficiency,
      an objective measure of sleep quality (low sleep efficiency < or =85%), and short
      sleep duration (< or =6.5 hours). The main outcome was prehypertension (> or
      =90th percentile for age, sex, and height), with systolic and diastolic blood
      pressures as continuous measures as secondary outcomes. Prehypertension, low
      sleep efficiency, and short sleep duration occurred in 14%, 26%, and 11% of the
      sample, respectively. In unadjusted analyses, the odds of prehypertension
      increased 4.5-fold (95% CI, 2.1 to 9.7) in adolescents with low sleep efficiency
      and 2.8-fold (95% CI, 1.1 to 7.3) in those with short sleep. In analyses adjusted
      for sex, body mass index percentile, and socioeconomic status, the odds of
      prehypertension increased 3.5-fold (95% CI, 1.5. 8.0) for low sleep efficiency
      and 2.5-fold (95% CI, 0.9 to 6.9) for short sleep. Adjusted analyses showed that
      adolescents with low sleep efficiency had on average a 4.0+/-1.2-mm Hg higher
      systolic blood pressure than other children (P<0.01). CONCLUSIONS: Poor sleep
      quality is associated with prehypertension in healthy adolescents. Associations
      are not explained by socioeconomic status, obesity, sleep apnea, or known
      comorbidities, suggesting that inadequate sleep quality is associated with
      elevated blood pressure.

PMID- 18711016
TI  - Feedback remodeling of cardiac potassium current expression: a novel potential
      mechanism for control of repolarization reserve.
AB  - BACKGROUND: Inhibition of individual K(+) currents causes functionally based
      compensatory increases in other K(+) currents that minimize changes in action
      potential duration, a phenomenon known as repolarization reserve. The possibility
      that sustained K(+) channel inhibition may induce remodeling of ion current
      expression has not been tested. Accordingly, we assessed the effects of sustained
      inhibition of one K(+) current on various other cardiac ionic currents. METHODS
      AND RESULTS: Adult canine left ventricular cardiomyocytes were incubated in
      primary culture and paced at a physiological rate (1 Hz) for 24 hours in the
      presence or absence of the highly selective rapid delayed-rectifier K(+) current
      (I(Kr)) blocker dofetilide (5 nmol/L). Sustained dofetilide exposure led to
      shortened action potential duration and increased repolarization reserve
      (manifested as a reduced action potential duration-prolonging response to I(Kr)
      blockade). These repolarization changes were accompanied by increased slow
      delayed-rectifier (I(Ks)) density, whereas I(Kr), transient-outward (I(to)),
      inward-rectifier (I(K1)), L-type Ca(2+) (I(CaL)), and late Na(+) current remained
      unchanged. The mRNA expression corresponding to KvLQT1 and minK (real-time
      polymerase chain reaction) was unchanged, but their protein expression (Western
      blot) was increased, suggesting posttranscriptional regulation. To analyze
      possible mechanisms, we quantified the muscle-specific microRNA subtypes miR-133a
      and miR-133b, which can posttranscriptionally regulate and repress KvLQT1 protein
      expression without affecting mRNA expression. The expression levels of miR-133a
      and miR-133b were significantly decreased in cells cultured in dofetilide
      compared with control, possibly accounting for KvLQT1 protein upregulation.
      CONCLUSIONS: Sustained reductions in I(Kr) may lead to compensatory upregulation
      of I(Ks) through posttranscriptional upregulation of underlying subunits, likely
      mediated (at least partly) by microRNA changes. These results suggest that
      feedback control of ion channel expression may influence repolarization reserve.

PMID- 18711017
TI  - Images in cardiovascular medicine. Right ventricular diastolic collapse by
      cardiac magnetic resonance imaging.

PMID- 18711018
TI  - Images in cardiovascular medicine. Evanescent asymmetrical septal hypertrophy and
      rapidly progressive heart failure in a 32-year-old man.

PMID- 18711019
TI  - Letter by Jong et al regarding article, "dietary fish and omega-3 fatty acid
      consumption and heart rate variability in US adults".

PMID- 18711021
TI  - Using magnetic resonance imaging to characterize recent myocardial injury:
      utility in acute coronary syndrome and other clinical scenarios.

PMID- 18711022
TI  - Is it time to update the definition of functional mitral regurgitation?:
      structural changes in the mitral leaflets with left ventricular dysfunction.

PMID- 18711023
TI  - Parasympathetic nervous system and heart failure: pathophysiology and potential
      implications for therapy.

PMID- 18711024
TI  - Some old and some new statistical tools for outcomes research.

PMID- 18711025
TI  - Images in cardiovascular medicine. Chronic cardiac transplant rejection:
      evaluation with magnetic resonance imaging.

PMID- 18711026
TI  - Cell cycle-dependent regulation of extra-adrenal glucocorticoid synthesis in
      murine intestinal epithelial cells.
AB  - Glucocorticoids are anti-inflammatory steroids with important applications in the
      treatment of inflammatory diseases. Endogenous glucocorticoids are mainly
      produced by the adrenal glands, although there is increasing evidence for extra
      adrenal sources. Recent findings show that intestinal crypt cells produce
      glucocorticoids, which contribute to the maintenance of intestinal immune
      homeostasis. Intestinal glucocorticoid synthesis is critically regulated by the
      transcription factor liver receptor homologue-1 (LRH-1). As expression of
      steroidogenic enzymes and LRH-1 is restricted to the proliferating cells of the
      crypts, we aimed to investigate the role of the cell cycle in the regulation of
      LRH-1 activity and intestinal glucocorticoid synthesis. We here show that either
      pharmacological or molecular modulation of cell cycle progression significantly
      inhibited expression of steroidogenic enzymes and synthesis of glucocorticoids in
      intestinal epithelial cells. Synchronization of intestinal epithelial cells in
      the cell cycle revealed that expression of steroidogenic enzymes is
      preferentially induced at the G(1)/S stage. Differentiation of immature
      intestinal epithelial cells to mature nonproliferating cells also resulted in
      reduced expression of steroidogenic enzymes. This cell cycle-related effect on
      intestinal steroidogenesis was found to be mediated through the regulation of LRH
      1 transcriptional activity. This mechanism may restrict intestinal glucocorticoid
      synthesis to the proliferating cells of the crypts.

PMID- 18711027
TI  - Initial evaluation of the use of USPIO cell labeling and noninvasive MR
      monitoring of human tissue-engineered vascular grafts in vivo.
AB  - This pilot study examines noninvasive MR monitoring of tissue-engineered vascular
      grafts (TEVGs) in vivo using cells labeled with iron oxide nanoparticles. Human
      aortic smooth muscle cells (hASMCs) were labeled with ultrasmall
      superparamagnetic iron oxide (USPIO) nanoparticles. The labeled hASMCs, along
      with human aortic endothelial cells, were incorporated into eight TEVGs and were
      then surgically implanted as aortic interposition grafts in a C.B-17 SCID/bg
      mouse host. USPIO-labeled hASMCs persisted in the grafts throughout a 3 wk
      observation period and allowed noninvasive MR imaging of the human TEVGs for real
      time, serial monitoring of hASMC retention. This study demonstrates the
      feasibility of applying noninvasive imaging techniques for evaluation of in vivo
      TEVG performance.

PMID- 18711028
TI  - Trastuzumab in inflammatory breast cancer.

PMID- 18711030
TI  - Perspective of West Africa: why bother to "mission"?

PMID- 18711029
TI  - Vitamin D intake and breast cancer risk: a case-control study in Italy.
AB  - BACKGROUND: Vitamin D has been suggested to play a protective role against
      several cancers, including breast cancer. PATIENTS AND METHODS: We used data from
      a case-control study conducted in Italy from 1991 to 1994 to study the relation
      between dietary intake of vitamin D and breast cancer risk. Subjects were 2569
      women with incident, histologically confirmed breast cancer and 2588 hospital
      controls. Odds ratios (ORs) and 95% confidence intervals (CIs) according to
      deciles of vitamin D intake were estimated by multiple logistic regression
      models. RESULTS: After allowance for major risk factors for breast cancer and
      dietary covariates including calcium and energy intake, there was no association
      with vitamin D up to the seventh decile. Thereafter, the OR declined, so that the
      overall trend was statistically significantly inverse. The OR for subjects in the
      three highest deciles of consumption compared with those in the lowest ones
      combined was 0.79 (95% CI 0.70-0.90). Intake of vitamin D >3.57 microg or 143 IU
      appeared to have a protective effect against breast cancer. The inverse
      association was consistent across strata of menopausal status. CONCLUSIONS: This
      study adds to the existing evidence that vitamin D intake in inversely associated
      with breast cancer risk.

PMID- 18711031
TI  - Trauma death: views of the public and trauma professionals on death and dying
      from injuries.
AB  - OBJECTIVES: To determine the values and preferences of the general public and
      trauma professionals regarding end-of-life care due to injury so as to inform
      practice guidelines. DESIGN, SETTING, AND PARTICIPANTS: Surveys of the general
      public sampled by random-digit dialing between June 6, 2005, and July 5, 2005,
      and of a convenience sample of trauma professionals during fall 2005 in the
      United States were conducted regarding preferences for care in the prehospital,
      emergency, and critical care settings. MAIN OUTCOME MEASURES: Responses to the
      survey questions. RESULTS: Most of the public and trauma professionals would
      prefer palliative care when doctors determine that aggressive critical care would
      not be beneficial in saving their lives. During resuscitation of an injured loved
      one, 51.9% of the public and 62.7% of the professionals would prefer to be in the
      emergency department treatment room. Most of the public believes that patients
      should have the right to demand care not recommended by their physicians. Most of
      both groups trust a doctor's decision to withdraw treatment when futility is
      determined. More of the public (57.4%) than the professionals (19.5%) believe
      that divine intervention could save a person when physicians believe treatment is
      futile. Other findings suggest further important insights. CONCLUSIONS: The
      results pose challenges that will require societal discourse to determine the
      best practice. Resolutions will need to be included in educational curricula and
      incorporated into practice to ensure that dying trauma victims and their families
      receive quality end-of-life care.

PMID- 18711032
TI  - Carotid endarterectomy as the criterion standard in high-risk elderly patients.
AB  - BACKGROUND: Carotid angioplasty and stenting (CAS) is now a viable alternative to
      carotid endarterectomy (CEA) in patients considered to be high-risk candidates
      for surgery, despite recent reports of increased adverse periprocedural outcomes
      in elderly patients. We sought to evaluate our single-institution experience and
      the 30-day perioperative outcomes of CEA in patients 75 years or older, who are
      traditionally considered high-risk surgical candidates and are recommended for
      CAS. DESIGN: Retrospective medical record review. SETTING: Academic tertiary care
      center. PATIENTS: All patients 75 years or older undergoing CEA during a 16-year
      period. MAIN OUTCOME MEASURES: Primary outcome of 30-day perioperative stroke,
      death, or myocardial infarction (MI) and a composite outcome of stroke, death, or
      MI. Secondary outcomes of all perioperative complications were exclusive of
      primary outcomes. RESULTS: One hundred seventeen CEAs were performed in 110
      patients 75 years or older. Significant medical comorbidities were well
      represented among the group. Among the patients, 50.4% were symptomatic, 60.7%
      had greater than 90% carotid stenosis, and 44.4% had contralateral disease.
      Primary outcome for any stroke, death, or MI was 1.7%, 0.9%, or 3.4%,
      respectively, with a composite event rate of any stroke or death of 2.6%. One or
      more secondary outcomes were experienced by 26.5% of patients. CONCLUSIONS:
      Carotid endarterectomy in elderly patients with significant comorbidities,
      traditionally thought to be a high-risk undertaking, is a safe procedure with
      periprocedural risks of stroke, death, and MI equivalent to those of younger
      patients. In light of the increased stroke risk in elderly patients with CAS, CEA
      remains the criterion standard for prevention of stroke in this patient
      population.

PMID- 18711033
TI  - Patterns of recurrence following liver resection for colorectal metastases:
      effect of primary rectal tumor site.
AB  - HYPOTHESIS: Patients with rectal adenocarcinoma are at increased risk of
      locoregional recurrence compared with patients with colon cancer. This may affect
      the pattern of recurrence and survival rates following hepatic resection of liver
      metastases from rectal adenocarcinoma. DESIGN: Retrospective review of a
      prospectively collected cancer center database. PATIENT AND METHODS: From April
      1, 1984, to December 31, 2005, 582 patients with liver metastases from a primary
      colorectal adenocarcinoma underwent hepatic resection. Clinical and pathological
      factors were analyzed using Cox regression analyses and log-rank tests. RESULTS:
      Of 582 patients, 141 (24.2%) had liver metastases from a primary rectal tumor
      site. Treatment of the primary rectal tumor most frequently included
      chemoradiation therapy (59.6%) and low anterior resection (63.1%). Most rectal
      tumors were pathological stage T3/T4 (85.8%) and N1 (68.1%). Treatment directed
      at the hepatic metastases included resection only (81.5%), resection plus
      radiofrequency ablation (17.8%), or radiofrequency ablation only (0.7%). With a
      median follow-up time of 30.7 months, 80 of 141 patients (56.7%) developed
      recurrence; 23 patients (16.3%) developed recurrence in the pelvis. Of 23
      patients with pelvic recurrence, 56.5% also developed recurrence in the liver.
      The 3- and 5-year survival rates for all patients were 62.4% and 36.4%,
      respectively. Of 80 patients who had a recurrence following hepatic metastectomy,
      23 (28.8%) underwent another operation. Following repeat metastectomy, 3- and 5
      year survival rates were 76.7% and 38.6%, respectively. CONCLUSIONS: Following
      resection of hepatic rectal metastases, pelvic recurrence is relatively common,
      and most patients with pelvic recurrence will also develop recurrence in the
      liver. Surgery for recurrent disease following hepatic resection of rectal
      metastases is warranted among well-selected patients.

PMID- 18711034
TI  - Stress and heart rate variability in surgeons during a 24-hour shift.
AB  - OBJECTIVE: To determine the specific effects of working long hours in surgery and
      potential cardiac stress in the individual surgeon by measuring heart rate
      variability (HRV). DESIGN, SETTING, AND PARTICIPANTS: This prospective study
      measured HRV before, during, and after a 24-hour shift in a standardized resting
      period of 10 minutes. Measurements were repeated over 10 shifts for each
      participant. Eight surgeons from a high-volume inner-city surgery department took
      part in the study. MAIN OUTCOME MEASURES: Time and frequency domain parameters of
      HRV as parameters of cardiac stress and correlations with perceived stress and
      fatigue on a visual analog scale. RESULTS: Perceived fatigue increased over 24
      hours (P < .001), whereas stress levels decreased slightly (P = .06). Time domain
      parameters of HRV increased from before the shift to after the shift (standard
      deviation of normal to normal intervals, square root of the mean normal to normal
      interval, and percentage of adjacent pairs of normal to normal intervals
      differing by more than 50 milliseconds: all P < .01), denoting more cardiac
      relaxation. Both the low- and high-frequency components increased (P = .04 and P
      < .001, respectively), showing a heightened activity of the autonomic nervous
      system. CONCLUSIONS: Measurements of HRV during a 24-hour surgical shift did not
      show an increase in cardiac stress concerning time domain parameters despite
      intense workloads for a median of 20 hours. Frequency components increased in
      parallel, though, suggesting alterations in sympathovagal balance. Perceived
      stress levels correlated with HRV, whereas fatigue did not. Further studies on
      occupational stress and its cardiac effects in surgeons are needed.

PMID- 18711035
TI  - Long-term results of subtotal vs total parathyroidectomy without
      autotransplantation in kidney transplant recipients.
AB  - HYPOTHESIS: Total parathyroidectomy without autotransplantation in kidney
      transplant recipients leads to reduced recurrence rates and similar improvement
      of clinical symptoms compared with subtotal parathyroidectomy. DESIGN: A
      retrospective cohort study. SETTING: University clinic. PATIENTS: Thirty-three
      patients with functioning renal grafts who underwent primary total (n = 17; group
      1) or subtotal (n = 16; group 2) parathyroidectomy for renal hyperparathyroidism.
      MAIN OUTCOME MEASURES: Long-term levels of intact parathyroid hormone, serum
      calcium, phosphate, alkaline phosphatase, creatinine, and vitamin D; bone pain;
      use of medication; and incidence of persistent or recurrent hyperparathyroidism.
      RESULTS: The mean length of follow-up was 31 months in group 1 and 41 months in
      group 2. In all patients, postoperative serum calcium and phosphate levels
      normalized and bone pain markedly decreased. Persistent hypocalcemia was not
      observed. Serum creatinine levels intermittently increased in both groups but
      returned to preoperative levels in most of the patients. In group 1, all patients
      had undetectable intact parathyroid hormone levels throughout the study period.
      In group 2, 2 patients had persistent and 3 patients developed recurrent
      hyperparathyroidism (31%) that required therapy with cinacalcet hydrochloride in
      3 cases. In 4 of these 5 patients, intact parathyroid hormone levels were greater
      than 54 ng/L directly after operation. In all, 27 of 33 patients (82%) received
      cholecalciferol therapy. Additional calcium supplementation was used by 12 group
      1 patients (71%) and 3 group 2 patients (19%). CONCLUSIONS: Total
      parathyroidectomy in kidney transplant recipients appears to be safe and
      protective against persistent and recurrent disease. If subtotal
      parathyroidectomy is performed, the remnant should be small.

PMID- 18711036
TI  - Evaluating the degree of difficulty of laparoscopic colorectal surgery.
AB  - OBJECTIVE: To quantify the degree of overall difficulty and the difficulty of
      each of the individual steps involved in the performance of laparoscopic
      colorectal procedures. The data should serve as a guide to surgeons in the early
      stages of their experience in laparoscopic colorectal surgery as to which
      procedures and steps to embark on first, to allow them to build experience in a
      stepwise fashion. METHODS: A mail-in survey of 35 experienced laparoscopic
      colorectal surgeons was conducted. Using a scale of 1 to 6, the surgeons were
      asked to rate the overall degree of difficulty of each of 12 laparoscopic
      colorectal procedures. Each procedure was then broken down into its key
      components (exposure, isolation of the vascular pedicle, dissection of the
      specimen, and anastomosis), and the raters were asked to individually grade each
      of these components for each intervention. An overall difficulty score was
      created for each procedure, as well as an individual difficulty score for each
      step. RESULTS: The response rate was 80%, representing a collective experience of
      approximately 6335 laparoscopic colorectal interventions. On the overall
      difficulty score, sigmoid colectomy achieved the lowest composite score of 2.0,
      while reversal of the Hartmann procedure scored the highest at 4.5. Analyzing the
      individual step complexity rating, mobilization of the splenic flexure scored
      highest, ahead of rectal mobilization. Vascular dissection scored significantly
      higher for right colectomy than for sigmoid resection, as did intracorporeal vs
      extracorporeal anastomosis for right colectomy. CONCLUSIONS: The learning curve
      for laparoscopic colorectal surgery is steep. This survey can help surgeons in
      the early part of this curve in their initial choice of procedure and allow them
      to build experience in a stepwise manner. This will help to identify achievable
      goals and develop strategies for reducing operating times and improving patient
      outcome by selecting appropriate cases at the outset.

PMID- 18711037
TI  - Four hundred consecutive total gastrectomies for gastric cancer: a single
      institution experience.
AB  - HYPOTHESIS: Although total gastrectomy (TG) has been generally accepted as the
      treatment of choice for upper and middle gastric cancers, some issues are still
      debated. The objective of this retrospective study was to analyze short- and long
      term results of TG (radical and palliative) in a series of 400 patients
      consecutively admitted to our surgical unit. DESIGN: Retrospective cohort study.
      SETTING: Primary and referral hospital care. PATIENTS: Hospital records of 400
      patients who consecutively underwent TG between January 1981 and June 2005 were
      reviewed. MAIN OUTCOME MEASURES: Surgical complications and survival. RESULTS:
      Three hundred twelve patients underwent radical procedures, and 88 patients
      underwent palliative procedures. The incidence of postoperative complications was
      higher among patients who underwent palliative TG (33 of 88 [37.5%]) compared
      with patients who underwent curative TG (75 of 312 [24.0%]) (P =.01). Mortality
      was higher among patients who underwent palliative TG (6 of 88 [6.8%]) compared
      with patients who underwent curative TG (11 of 312 [3.5%]) (P =.18). Five-year
      survival was 61.8% after curative TG and 12.8% after palliative TG. Ten-year
      survival was 47.3% after curative TG and 0.0% after palliative TG. CONCLUSIONS:
      This study among 400 consecutive patients who underwent TG at the same surgical
      unit shows that this surgical procedure in experienced hands can lead to
      excellent short- and long-term results.

PMID- 18711038
TI  - Undertriage of elderly trauma patients to state-designated trauma centers.
AB  - OBJECTIVE: To determine whether age bias is a factor in triage errors. DESIGN:
      Retrospective analysis of 10 years (1995-2004) of prospectively collected data in
      the statewide Maryland Ambulance Information System followed by surveys of
      emergency medical services (EMS) and trauma center personnel at regional EMS
      conferences and level I trauma centers, respectively. PATIENTS: Trauma patients
      were defined as those who met American College of Surgeons physiology, injury,
      and/or mechanism criteria and were subjectively declared priority I status by EMS
      personnel. MAIN OUTCOME MEASURE: Undertriage, defined as when trauma patients
      were not transported to a state-designated trauma center. RESULTS: The registry
      analysis identified 26 565 trauma patients. The undertriage rate was
      significantly higher in patients aged 65 years or older than in younger patients
      (49.9% vs 17.8%, P < .001). On multivariate analysis, this decrease in trauma
      center transports was found to start at age 50 years (odds ratio, 0.67; 95%
      confidence interval, 0.57-0.77), with another decrease at age 70 years (odds
      ratio, 0.45; 95% confidence interval, 0.39-0.53) compared with patients younger
      than 50 years. A total of 166 respondents participated in the follow-up surveys
      and ranked the top 3 causal factors for this undertriage as inadequate training,
      unfamiliarity with protocol, and possible age bias. CONCLUSIONS: Even when trauma
      is recognized and acknowledged by EMS, providers are consistently less likely to
      consider transporting elderly patients to a trauma center. Unconscious age bias,
      in both EMS in the field and receiving trauma center personnel, was identified as
      a possible cause.

PMID- 18711039
TI  - Demographics, treatment, and early outcomes in penetrating vascular combat
      trauma.
AB  - OBJECTIVES: To describe arterial and venous injuries and their management and
      short-term outcomes in a wartime hospital. DESIGN: Retrospective review of
      patients with vascular injuries. Mechanism, location, method of repair, and
      outcomes were analyzed with descriptive and inferential statistics. SETTING: The
      31st Combat Support Hospital, Operation Iraqi Freedom. PATIENTS: A total of 153
      patients with 218 vascular injuries from January 1, 2004, to December 30, 2004.
      MAIN OUTCOME MEASURES: Limb salvage and mortality rates. RESULTS: The overall
      limb salvage rate was 80%, while all-cause mortality was 6%. Most vascular
      injuries were sustained by blast and fragmentation mechanisms. Not surprisingly,
      most vascular injuries were in lower extremity vessels (57% arterial, 50%
      venous), with a high predominance of superficial femoral vessel injuries.
      Vascular injuries to the upper extremities were associated with a higher limb
      salvage rate (95%) than injuries to the lower extremities (71%). Variable follow
      up data for 63 (41%) patients revealed that 32 underwent further procedures
      outside the combat theater, 12 of which were delayed amputations. Of all arterial
      injuries, 36% were primarily repaired, 34% were repaired with a vein
      interposition graft, 29% were ligated, and 2% were repaired with a prosthetic
      graft. A majority of venous injuries (56%) were ligated. CONCLUSIONS: There is an
      acceptable early patency and limb salvage rate in combat vascular repairs. A
      majority of penetrating vascular injuries occur in the lower extremities.
      Overall, penetrating vascular trauma is often a survivable injury.

PMID- 18711040
TI  - Meta-analysis of randomized studies evaluating chewing gum to enhance
      postoperative recovery following colectomy.
AB  - OBJECTIVE: To compare outcomes following abdominal surgery with or without the
      use of chewing gum in the early postoperative period. DATA SOURCES: MEDLINE,
      Embase, Ovid, and Cochrane databases. STUDY SELECTION: Randomized controlled
      trials reporting 1 or more outcomes related to functional postoperative recovery.
      Study quality was assessed using a validated scale. DATA EXTRACTION: Time to the
      first passage of flatus, time to first bowel movement, and length of
      postoperative stay. DATA SYNTHESIS: Five trials (158 patients) satisfied the
      inclusion criteria. Time (in days) for the patient to pass flatus (weighted mean
      difference [WMD], - 0.66; 95% confidence interval [CI], - 1.11 to - 0.20; P =
      .005) and the time until the first bowel movement (WMD, - 1.10; 95% CI, - 1.79 to
      - 0.42; P = .002) were significantly reduced in the chewing gum group compared
      with controls. However, both of these results demonstrated significant
      heterogeneity. Postoperative length of stay was also reduced in the chewing gum
      group by longer than 1 day (WMD, - 1.25; 95% CI, - 3.27 to 0.77; P = .23);
      however, this result was not statistically significant. This result was
      significant when studies that explicitly included patients with stomas being
      formed during the surgery were excluded (WMD, - 2.46; 95% CI, - 3.14 to - 1.79; P
      < .001), with no significant heterogeneity. CONCLUSIONS: Chewing gum may enhance
      intestinal recovery following colectomy and reduce the length of hospital stay.
      Owing to the potential for substantial cost savings, larger-scale, blinded,
      randomized controlled trials with placebo arms are warranted.

PMID- 18711041
TI  - Spontaneous duodenal hematoma: a rare cause of upper gastrointestinal tract
      obstruction.
AB  - Intramural duodenal hematoma is a rare cause of proximal gastrointestinal tract
      obstruction most frequently encountered in the setting of abdominal trauma or
      coagulation deficiencies. Here we report a case of a 75-year-old man who
      spontaneously developed an intramural duodenal hematoma with no apparent inciting
      event or risk factors.

PMID- 18711042
TI  - Trauma and coagulopathy: a new paradigm to consider.

PMID- 18711043
TI  - Image of the month. Benign portal venous gas.

PMID- 18711044
TI  - Image of the month. Reactive lymphoid hyperplasia.

PMID- 18711045
TI  - Do not forget organ and tissue donation.

PMID- 18711046
TI  - Notice of duplicate publication: "pathogenesis of Barrett esophagus: deoxycholic
      acid up-regulates goblet-specific gene MUC2 in concert with CDX2 in human
      esophageal cells" (Arch Surg. 2007;142 [6]:540-545).

PMID- 18711047
TI  - Lack of evidence for adrenal insufficiency after single-dose etomidate.

PMID- 18711048
TI  - Roux-en-Y after gastric bypass.

PMID- 18711052
TI  - Methodological and statistical problems in uvulopalatopharyngoplasty research: a
      follow-up study.
AB  - OBJECTIVES: To review the published literature on uvulopalatopharyngoplasty
      (UPPP) and assess the methodological quality of the research and compare it with
      a similar article published in 1995; and to determine what, if any, improvement
      in the methodological quality of the research resulted during the ensuing 10
      years. DESIGN: Methodological and statistical evaluation of the published
      literature on UPPP. Thirty articles representing the clinical studies on UPPP and
      related procedures written from January 1996 to August 2005 were reviewed. Only
      articles reporting polysomnography data were included. RESULTS: Overall, the
      articles demonstrated fair methodological and statistical quality. Compared with
      the previous review by Schechtman et al, there was a slight increase in the
      number of articles that discussed statistical power and reported confidence
      intervals. There were increases in the mean sample size, the percentage of
      randomized controlled studies, the number of end points, and the use of validated
      subjective outcome measures; longer mean follow-up time; and more complete
      reporting of age and sex information. There was no increase in the percentage of
      published studies that used a prospective study design. None of the studies that
      required minimum acceptable baseline values of objective sleep parameter measures
      for enrollment indicated the use of separate screening and baseline assessments.
      There were 7 different definitions of sleep apnea and 17 different definitions of
      success in treatment. CONCLUSIONS: There has been an overall improvement in the
      quality of the articles published on UPPP since 1995. Several areas still need
      improvement: use of more prospective studies, decrease in number of end points,
      use of separate screening and baseline assessments, and consensus in the
      definitions of sleep apnea and success.

PMID- 18711053
TI  - The effects of smoking on the rate of postoperative hemorrhage after
      tonsillectomy and uvulopalatopharyngoplasty.
AB  - OBJECTIVE: To evaluate the rate of posttonsillectomy hemorrhage and any change
      that smoking causes in patients who undergo tonsillectomy. DESIGN: Retrospective
      chart review. SETTING: Military tertiary referral center. PATIENTS: The study
      included 1036 adult patients who underwent tonsillectomy either alone or in
      conjunction with another procedure. MAIN OUTCOME MEASURES: The rate of
      postoperative hemorrhage was reviewed in all patients who underwent tonsillectomy
      at our medical center, and an investigation was conducted to determine whether
      smoking caused any alteration in this rate. RESULTS: A total of 1010 patients
      were included in the study, with a total bleeding rate of 6.7%. There was a
      significant increase in the rate of bleeding in all patients when they were
      divided into smokers and nonsmokers (10.2% and 5.4%, respectively; P = .01). The
      large difference was found by subset analysis to be attributable to a marked
      increase in postoperative hemorrhage in the patients who underwent
      uvulopalatopharyngoplasty (10.9% in smokers vs 3.3% in nonsmokers; P = .006) and
      remained significant when they were further subdivided by sex. Men who underwent
      tonsillectomy alone also bled significantly more than women (11.2% and 5.4%,
      respectively; P = .02). All other subsets analyzed did not reach statistical
      significance. CONCLUSIONS: Smoking does appear to increase the rate of
      posttonsillectomy hemorrhage in patients who undergo uvulopalatopharyngoplasty
      with tonsillectomy, but not in those who undergo tonsillectomy alone. This
      modifiable risk factor may help clinicians further counsel their patients before
      surgery, but further study is needed to ascertain that these findings apply to a
      broader patient base.

PMID- 18711054
TI  - Histopathological changes after coblation inferior turbinate reduction.
AB  - OBJECTIVE: To assess the medium- to long-term histopathological changes after
      coblation (cold ablation) inferior turbinate (IT) reduction (CITR) surgery for
      refractory IT hypertrophy. DESIGN: Two-center, prospective, nonrandomized,
      controlled histological study. SETTING: University-affiliated hospitals.
      PATIENTS: The coblation-treated group included 22 samples from 16 men with IT
      hypertrophy in whom CITR had failed and who underwent endoscopically guided
      mucotomy. The control group included 18 samples from 14 men who had nasal
      obstruction due to refractory IT hypertrophy and who had undergone inferior
      turbinectomy. MAIN OUTCOME MEASURES: After processing the samples of both groups,
      we assessed the general histopathological features, the area fraction of various
      soft-tissue constituents, and the epithelial integrity. RESULTS: Qualitative
      analysis showed marked fibrosis and depletion of submucosal glands and venous
      sinusoids in the lamina propria after CITR. Compared with the control group, the
      coblation-treated group showed a significantly increased area fraction of
      connective tissue and a significantly decreased area fraction of submucosal
      glands and venous sinusoids (P < .001 for all 3 comparisons). A significantly
      decreased relative proportion of intact epithelium and a significantly increased
      relative proportion of partial epithelial shedding were also found in the
      coblation-treated group (P = .03 and P = .04, respectively). CONCLUSIONS: The
      long-term histological effects of CITR were significant fibrosis, glandular and
      venous sinusoid depletion, and partial epithelial shedding. The latter probably
      resulted from vascular damage, causing a reduction in epithelial perfusion.
      Questions remain concerning the long-term implications of the histopathological
      changes of CITR on nasal physiology.

PMID- 18711055
TI  - Expression of cyclooxygenase and lipoxygenase enzymes in sinonasal mucosa of
      patients with cystic fibrosis.
AB  - OBJECTIVE: To evaluate the expression of cyclooxygenase (COX) and lipoxygenase
      (LO) enzymes in the sinonasal mucosa of patients with cystic fibrosis (CF).
      DESIGN: Immunohistochemical staining of archived tissue. PARTICIPANTS: Specimens
      from 9 patients with CF were analyzed; control specimens were obtained from 4
      patients without a history of CF or rhinosinusitis. INTERVENTIONS: Expression of
      the enzymes COX-1, COX-2, 5-LO, 12-LO, and 15-LO was evaluated with the use of
      immunohistochemical techniques in archived sinonasal mucosal tissue from patients
      with CF. These results were compared with those of the control group. RESULTS: We
      noted the characteristic staining patterns of epithelium and submucosal glands
      for each enzyme. Statistically significant (P < .05) differences between control
      and CF specimens were noted in the staining intensity of columnar epithelium for
      COX-2 (cytoplasm) and 12-LO (cytoplasm and nucleus) and of submucosal glands for
      COX-2 (cytoplasm) and 12-LO (cytoplasm). No significant differences were noted
      for the staining intensity of COX-1, 5-LO, or 15-LO between the groups.
      CONCLUSIONS: Significant differences in sinonasal mucosal expression of COX-2 and
      12-LO enzymes exist between patients with CF and controls. This suggests a
      difference in arachidonic acid metabolism between these 2 groups.

PMID- 18711056
TI  - Effect of improved nasal airflow after adenoidectomy on nasal erectile tissue.
AB  - OBJECTIVE: To determine the effect of improved nasopharyngeal airflow after
      adenoidectomy on nasal turbinate erectile tissue in pediatric patients. DESIGN:
      Clinical, prospective, before-and-after study. SETTING: Pediatric Otolaryngology
      Clinic at Hospital da Crianca Santo Antonio de Porto Alegre (Complexo Hospitalar
      Santa Casa de Porto Alegre). PATIENTS: Twenty-one 5- to 11-year-old children
      diagnosed as having severe nasal obstruction, with an indication for
      adenoidectomy. INTERVENTION: Adenoidectomy. MAIN OUTCOME MEASURES: Acoustic
      rhinometry data before and 90 days after surgery. To specifically monitor
      erectile tissue behavior, only the volume of the nasal turbinate region was
      considered (depth, 2.20-5.40 cm). RESULTS: The volume of the turbinate region
      varied from 6.03 cm(3) in the preoperative evaluation to 6.99 cm(3) in the
      postoperative evaluation, representing an increase of 16% (P < .04). Multiple
      linear and logistic regressions did not reveal any factors other than
      adenoidectomy that could explain this change. CONCLUSIONS: Because the only
      possible explanation for the observed erectile tissue changes was improvement in
      nasal airflow, we can assume that adenoidectomy favorably affects the behavior of
      nasal erectile structures and is associated with a decrease in turbinate size.
      Combined turbinate reduction and adenoidectomy should not be the rule because
      children may benefit from adenoidectomy alone.

PMID- 18711057
TI  - Comparison of Pediatric Voice Outcome Survey, Reflux Symptom Index, Reflux
      Finding Score, and esophageal biopsy results.
AB  - OBJECTIVE: To examine correlations between the Pediatric Voice Outcome Survey
      (PVOS) score, the Reflux Symptom Index (RSI) score, the Reflux Finding Score
      (RFS), and esophageal biopsy findings in children undergoing upper aerodigestive
      tract endoscopy. DESIGN: Retrospective review of pediatric voice quality-of-life
      and laryngopharyngeal reflux surveys. Blinded assessment of endoscopic laryngeal
      images. SETTING: Tertiary care children's hospital. PATIENTS: The study included
      36 children with the primary problem of dysphonia (n = 28) or cough (n = 8) who
      underwent endoscopy. INTERVENTIONS: The PVOS and the RSI were administered to the
      patient's parents before surgery. The patients underwent
      laryngotracheobronchoscopy and esophageal biopsy. Four raters independently
      assigned an RFS to the laryngeal photographs. MAIN OUTCOME MEASURES: The
      assessment included (1) PVOS scores, RSI scores, and RFSs; (2) internal
      consistency of PVOS and RSI scores; (3) RFS intrarater and interrater
      reliability; and (4) correlations between PVOS score, RSI score, RFS, and
      esophageal biopsy findings. RESULTS: The mean (SD) age of the patients was 7.5
      (2.6) years; the mean (SD) PVOS score, 71.9 (21.4); and the mean (SD) RSI score,
      16.2 (9.1). The PVOS and the RSI scores demonstrated good internal consistency
      (Cronbach alpha = 0.79 and 0.78, respectively). The RFS exhibited good intrarater
      reliability (r = 0.66-0.98) and moderate interrater reliability (r = 0.32-0.70).
      The PVOS and RSI instruments displayed significant correlation (r = -0.30; P =
      .04). There were no other significant correlations between RFSs, esophageal
      biopsy results, PVOS scores, or RSI scores (P > .05). CONCLUSIONS: The RSI may be
      a useful parent-proxy instrument in addition to the PVOS for pediatric voice
      patients. The RFS is reliable in children, but its validity could not be
      demonstrated in this patient population.

PMID- 18711058
TI  - Nasal septal abscess in children: reconstruction with autologous cartilage grafts
      on polydioxanone plate.
AB  - OBJECTIVE: To assess outgrowth and aesthetics of the nose in children after
      reconstruction of the cartilaginous nasal septum with autologous cartilage grafts
      on polydioxanone plate. DESIGN: Prospective nonrandomized case series. SETTING:
      University hospital. PATIENTS: Six patients (5 boys and 1 girl), aged 3 to 11
      years, with nasal septal abscess. INTERVENTION: The nasal septa of 6 children
      with a history of nasal septal abscess and partial or complete destruction of
      nasal septal cartilage were reconstructed with autologous cartilage grafts of the
      auricle or rib fixed on polydioxanone plate. MAIN OUTCOME MEASURES: Nasal
      outgrowth was measured by the length of the nose and by the amount of nasal tip
      projection and was compared with standardized growth curves. Aesthetic outcome
      variables included nasolabial angle, columellar retraction, and development of
      saddle nose deformity and were classified as normal, mild, or severe. RESULTS:
      The duration of follow-up ranged from 10 to 68 months (mean follow-up, 38
      months). Four children had complete loss of the cartilaginous septum. Areas 1 and
      2 (caudal parts) had been destroyed in 2 children. Auricular cartilage was used
      in 5 children; costal cartilage was needed in 1 child. Compared with standardized
      growth curves, the length of the nose and the amount of nasal tip projection were
      within 1 SD in all children. None of the children developed saddle nose
      deformity. One child had mild columellar retraction; 3 children had mild
      overrotation of the nasal tip. CONCLUSION: Total reconstruction of abscess
      induced destruction of nasal septal cartilage with autologous cartilage grafts
      fixed on polydioxanone plate has, so far, resulted in normal development of the
      nose during follow-up, without expected aesthetic problems.

PMID- 18711059
TI  - Treatment of congenital subglottic hemangiomas: our experience compared with
      reports in the literature.
AB  - OBJECTIVE: To evaluate the outcome of our experience in the treatment of
      congenital subglottic hemangiomas. DESIGN: Retrospective review of records.
      SETTING: Airway tertiary care service. PATIENTS: From 1986 to 2006 we treated 39
      pediatric patients affected by congenital subglottic hemangiomas. INTERVENTION:
      Therapeutic choice depended on presentation symptoms and grade of respiratory
      obstruction: 6 patients were primarily treated with only systemic steroids; 11
      patients underwent intralesional corticosteroid injections followed by tracheal
      intubation and systemic steroid support; and 22 patients underwent primary diode
      laser treatment. MAIN OUTCOME MEASURE: The outcomes were evaluated according to 1
      or more of the following criteria: resolution of symptoms, reduction of airway
      obstruction, the need and duration of intubation, tracheotomy decannulation, need
      of further treatments, and occurrence of complications. RESULTS: Patients treated
      with only systemic steroids showed a success rate of 50% (3 of 6); patients who
      underwent intralesional corticosteroid injections followed by tracheal intubation
      and systemic steroid support reached a positive result in 73% of cases (8 of 11).
      On the whole, 18% of patients treated with full-dose systemic steroids developed
      significant adverse effects (3 of 17). The success rate was 95% among patients
      treated with diode laser as primary treatment (21 of 22), with a complication
      rate of 9% (2 of 22). CONCLUSIONS: Endoscopic laser surgery is the therapeutic
      option that most approaches the objectives of securing the airway while using the
      least invasive method possible and reducing to a minimum the necessity and
      duration of intubation. On the basis of our experience, we believe that diode
      laser, owing to its physical and structural features, is the safest and most
      effective device for the treatment of congenital subglottic hemangiomas.
      Treatment with intralesional or systemic corticosteroids could have an adjuvant
      role.

PMID- 18711060
TI  - Matrix metalloproteinase-2 gene polymorphisms in nasal polyps.
AB  - OBJECTIVE: To systematically investigate the role of matrix metalloproteinase-2
      (MMP2) tagging single nucleotide polymorphisms (SNPs) and promoter functional
      polymorphism in the development of nasal polyps in a Chinese population in
      Taiwan. DESIGN: We conducted a case-control study in 136 cases of chronic
      rhinosinusitis with bilateral nasal polyps and 136 controls. Seventeen SNPs were
      selected, including 16 tagging SNPs and 1 promoter functional SNP. The genotypes
      were determined by TaqMan technology. Hardy-Weinberg equilibrium was tested for
      each SNP, and genetic effects were evaluated according to 3 modes of inheritance.
      Subset analysis based on the recurrence of nasal polyps was also performed.
      SETTING: Medical university center hospital. RESULTS: All 17 SNPs were in Hardy
      Weinberg equilibrium. When comparing the patients with recurrent nasal polyps and
      controls, none of the SNPs reached the significant level of P < .05 except
      rs857403. The AT genotype of rs857403 had an adjusted odds ratio of 2.07 (95%
      confidence interval, 1.09-3.95) (P = .03). However, the result became
      nonsignificant after including an additional 691 controls. Therefore, we
      considered that the initial significance was a false-positive finding. Neither
      haplotype analysis nor subset analysis yielded any significant result.
      CONCLUSION: The MMP2 gene does not play a crucial role in conferring risk for
      nasal polyps in a Taiwanese population.

PMID- 18711061
TI  - Swallowing function in patients with base of tongue cancers treated with primary
      surgery and reconstructed with a modified radial forearm free flap.
AB  - OBJECTIVE: To report swallowing outcomes and biomechanical properties of the base
      of the tongue (BOT) and the posterior pharyngeal wall (PPW) in patients who
      undergo surgical reconstruction with the beavertail modification of radial
      forearm free flap after primary resection of BOT cancer. DESIGN: Prospective
      cohort study with a 1-year minimum follow-up performed between October 1, 2001,
      and August 31, 2005. SETTING: Tertiary care facility. PATIENTS: Patients
      diagnosed as having primary carcinoma of the BOT were treated with primary
      surgical resection and reconstruction followed by radiotherapy. Inclusion
      criteria were collection of videofluoroscopic swallowing study (VFSS) data before
      and 1 year after surgery. Forty-one patients were treated during a 5-year period,
      and 20 were included in the final analysis. INTERVENTIONS: Reconstruction of BOT
      defects with the beavertail modification of radial forearm free flap followed by
      postoperative radiation. MAIN OUTCOME MEASURES: Aspiration score, pharyngeal
      residue score, and biomechanical analysis of BOT and PPW mobility were performed
      using images from VFSSs. Both the BOT and PPW positions were measured from 2
      static bony landmarks. RESULTS: Of the 20 patients in the final analysis, 19
      (95%) were able to swallow safely at 1 year. Mobility of the BOT after surgery
      was reduced in all postoperative VFSS data. Anteroposterior dimension or bulk of
      the BOT was preserved. No significant difference was found in PPW mobility.
      CONCLUSIONS: The beavertail modification of the radial forearm free flap is a
      good reconstructive option after BOT cancer extirpation. The procedure preserves
      the bulk of the BOT after cancer treatment and maintains adequate BOT-PPW
      apposition. This allows structures such as the pharyngeal, oral, and suprahyoid
      musculature to contract and generate the necessary force to propel the food bolus
      through the oropharynx, resulting in a safe swallow.

PMID- 18711062
TI  - Improved outcomes in patients with head and neck cancer using a standardized care
      protocol for postoperative alcohol withdrawal.
AB  - OBJECTIVE: To show clinical benefit in the main outcome measures by the use of a
      standardized protocol for identification, characterization, and treatment of
      alcohol withdrawal syndrome (AWS) in postoperative patients with head and neck
      cancer. DESIGN: Prospective cohort study with a retrospective cohort control.
      SETTING: Tertiary care university. PATIENTS: A total of 26 consecutive
      postoperative patients with AWS were selected from among 652 patients with head
      and neck cancer to be enrolled in the protocol from March 2003 through March
      2005. Controls consisted of 14 of 981 consecutive patients with AWS from March
      2000 through December 2002. INTERVENTION: Application of a standardized care
      protocol. MAIN OUTCOME MEASURES: Sensitivity and specificity of preoperative
      screening for AWS risk, predictability of outcomes, length of stay, transfers to
      the intensive care unit (ICU), AWS symptoms, postoperative morbidity and
      mortality, doses of pharmacotherapy required, and charges. RESULTS: Protocol
      patients demonstrated significantly fewer AWS-related ICU transfers and less
      delirium and violence than preprotocol patients. Mortality, wound complications,
      hospital charges, and doses of benzodiazepines, clonidine, and haloperidol were
      not significantly different between these 2 groups. Preoperative medical history
      correlated poorly with AWS outcomes. Screening was 87.5% sensitive and 99.7%
      specific. Late enrollees to the protocol (false-negative screening results)
      showed many significantly worse outcomes than immediate enrollees. CONCLUSION:
      Use of the standardized AWS symptom-triggered protocol decreased delirium,
      violence, and AWS-related ICU transfers without significantly increasing hospital
      charges.

PMID- 18711063
TI  - The Jahrsdoerfer grading scale in surgery to repair congenital aural atresia.
AB  - OBJECTIVE: To determine the predictive ability of the Jahrsdoerfer grading scale
      score in congenital aural atresia surgery. DESIGN: Retrospective review of
      medical records. SETTING: Tertiary referral center. PATIENTS: One hundred eight
      patients with aural atresia. MAIN OUTCOME MEASURES: Demographic data,
      preoperative Jahrsdoerfer score, and postoperative audiometric outcomes were
      reviewed. One month postoperative, 4-tone pure-tone averages and speech reception
      thresholds were compared between ears scoring 6 or lower, 7, and 8 or higher on
      the Jahrsdoerfer grading scale. The percentage of ears with a speech reception
      threshold of 30 dB hearing level or lower for each group was calculated and
      compared between groups. Individual anatomical structures on the Jahrsdoerfer
      grading scale were evaluated for their ability to predict postoperative
      audiometric success. RESULTS: Of 116 ears evaluated, postoperative 4-tone pure
      tone averages and speech reception thresholds were significantly poorer in ears
      scoring 6 or less on the Jahrsdoerfer grading scale compared with ears scoring 7
      or higher (P < .02, t test). Ears scoring 6 or less had a 45% chance of achieving
      a postoperative speech reception threshold of 30 dB hearing level or lower, while
      ears scoring 7 or higher had an 89% chance (P < .01, chi(2) test). Lack of middle
      ear aeration was the only anatomical factor predictive of poor audiometric
      outcome. CONCLUSIONS: Compared with patients with a Jahrsdoerfer score of 6 or
      lower, patients with a score of 7 or higher had significantly better hearing
      postoperatively. Middle ear aeration may be the most important predictor of
      postoperative hearing outcome. The Jahrsdoerfer grading scale is an invaluable
      tool in the preoperative evaluation of patients with congenital aural atresia.

PMID- 18711064
TI  - Soft-tissue reconstruction for atypical microtia malformations and trauma.
AB  - OBJECTIVE: To provide customized reconstructions of atypical microtia
      malformations and trauma via 1- or 2-stage procedures. DESIGN: Case reports.
      SETTING: Academic otolaryngology specialty hospital. PATIENTS: Pediatric patients
      with rare and unique ear malformations. INTERVENTIONS: Customized auricular
      reconstruction using contralateral postauricular donor grafts (skin and
      cartilage) as well as ipsilateral tissue (flaps and bone). MAIN OUTCOME MEASURES:
      Postoperative results. RESULTS: Surgical procedures were completed in 1 or 2
      stages with minimal morbidity. No donor scars were visible, in contrast to
      traditional reconstructive methods. The completed auricular appearance was
      realistic. CONCLUSION: Selected patients can benefit from soft-tissue
      reconstruction of the auricle that feels normal to the touch and lacks the
      morbidity and scarring of traditional reconstructive methods.

PMID- 18711065
TI  - Polyethylenimine-mediated cochlear gene transfer in guinea pigs.
AB  - OBJECTIVE: To demonstrate and compare polycationic-mediated cochlear gene
      transfer with linear polyethylenimine (PEI) via cochleostomy and osmotic pump
      infusion method. DESIGN: A dissociated cochlear culture was used to select the
      optimum nitrogen to phosphate ratio of PEI/DNA complexes to be used in vivo. The
      PEI-enhanced green fluorescent protein reporter gene DNA complex was introduced
      with single inoculation (cochleostomy) or with sustained delivery (osmotic pump
      method) into guinea pig cochleas and examined for transgene expression. SUBJECTS:
      Male Albino Hartley guinea pigs (250-350 g). RESULTS: The relatively low
      transfection efficiency of PEI limits its potential when compared with viral
      counterparts; however, sustained release of the vector solution was able to
      improve PEI's transfection efficiency. The PEI-infused cochleas maintained intact
      cellular and tissue architecture with absence of inflammation. Transfection
      confined to the perilymphatic space highlights the need to target the gene vector
      into the scala media if transfection is targeted at cells within the organ of
      Corti. CONCLUSION: These findings indicate that PEI is able to transfect the
      cochlea in vivo with sustained delivery and present an alternative for nonviral
      cochlear gene therapy.

PMID- 18711066
TI  - Multiple adult rhabdomyomas of the oropharynx, base of the tongue, and floor of
      the mouth: magnetic resonance findings.

PMID- 18711067
TI  - Radiology quiz case. "Teflonoma" of the thyroid and the soft tissues of the neck.

PMID- 18711068
TI  - Pathology quiz case. Dermatofibrosarcoma protuberans (DFSP) of the scalp.

PMID- 18711069
TI  - Successful treatment of trigeminal trophic syndrome in a 6-year-old boy with
      negative pressure wound therapy.

PMID- 18711070
TI  - A community-based study of acne-related health preferences in adolescents.
AB  - OBJECTIVE: To examine preferences for acne-related outcomes in adolescents.
      DESIGN: Community-based, cross-sectional survey study. SETTING: Four public high
      schools in San Francisco, California. PARTICIPANTS: Volunteer sample of 266
      adolescents with acne. MAIN OUTCOME MEASURES: Health utilities for current acne
      state and 3 hypothetical acne-related states (100% clearance, 50% clearance, and
      100% clearance but with residual scarring) using time trade-off (TTO) and
      willingness to pay metrics. A self-administered written survey was used. RESULTS:
      The mean (median) utilities for current acne state using the TTO metric was 0.961
      (0.985). One hundred percent acne clearance received a higher utility score (mean
      [median] score, 0.978 [0.994]) than 50% clearance (0.967 [0.992]; P < .001 by
      Wilcoxon signed rank test) and 100% clearance with scarring (0.965 [0.992]; P <
      .001). Although current acne state utility was not correlated with physician
      rated severity (P = .23), a significant association with subject-rated severity
      was observed in both univariate analysis (P = .01) and after adjustment for
      duration of acne, having seen a physician for acne, and income (P = .05).
      Adolescents were willing to pay a median of $275 to have never had acne in their
      lifetime and were willing to pay significantly more for 100% clearance than for
      50% clearance or 100% clearance but with scarring (P < .001 for both
      comparisons). CONCLUSIONS: We describe adolescents' acne-related health state
      utilities. Compared with current acne state utility, both partial and total
      clearance with scarring are substantially less preferable than total clearance.
      Subjects' self-rated disease severity correlates with current acne state utility,
      whereas physician-rated severity does not. A self-administered paper instrument
      can effectively assess adolescents' acne-related preferences in community-based
      samples.

PMID- 18711071
TI  - Retrospective evaluation of patch testing before or after metal device
      implantation.
AB  - OBJECTIVE: To review the results of patch testing before or after metal device
      implantation. DESIGN: Retrospective medical chart review. SETTING: Tertiary care
      academic medical center. PATIENTS: All patients who underwent patch testing
      before or after metal device implantation. INTERVENTIONS: Patch testing. RESULTS:
      From January 1999 through March 2006, 44 patients underwent patch testing in
      conjunction with metal device implantation, 22 preoperatively and 22
      postoperatively. The reason for preoperative patch testing was a history of
      allergy to metals. Five patients had positive results for a component of the
      proposed device. The reasons for postoperative patch testing were unexplained
      skin eruptions at the implantation site (13 patients), chronic joint pain (8
      patients), and joint loosening (1 patient). None of the patients had positive
      patch test results to a component of the previously implanted device.
      CONCLUSIONS: Although the numbers of patients in this study were small, patch
      testing performed before metal device implantation was helpful in guiding the
      choice of device selected. Patch testing after implantation was of limited value.

PMID- 18711072
TI  - Trichoscopy.

PMID- 18711074
TI  - Global warming and its effect on dermatology and plants.

PMID- 18711073
TI  - High association of human herpesvirus 8 in large-plaque parapsoriasis and mycosis
      fungoides.
AB  - OBJECTIVE: To investigate the presence of human herpesvirus 8 (HHV-8) in lesional
      skin of German patients with large-plaque parapsoriasis (LPP) or mycosis
      fungoides (MF). The pathogenetic relevance of HHV-8 in cutaneous T-cell lymphoma
      is controversial. Recently, a highly significant association of HHV-8 in LPP was
      found, which suggests a role in the pathogenesis of this disease. DESIGN:
      Retrospective study of the presence of HHV-8 in German patients with
      lymphoproliferative diseases. SETTING: Dermatologic clinic at a university
      hospital of the Ruhr University Bochum, Bochum, Germany. PATIENTS: Fifty-three
      patients treated for lymphoproliferative skin diseases were included in the
      study, including 14 patients with LPP, 31 with different stages of MF, and 8 with
      lymphomatoid papulosis (LyP). Twenty-three patients with Kaposi sarcoma (KS) made
      up the positive control group, and 10 patients with atopic dermatitis served as
      negative controls. MAIN OUTCOME MEASURES: The presence of HHV-8 was analyzed from
      paraffin-embedded lesional tissue samples using a nested polymerase chain
      reaction for the open reading frame (ORF) 26 and with immunohistochemical
      staining for the latency-associated nuclear antigen (LANA) encoded by ORF 73.
      RESULTS: A high association of HHV-8 infection in both lymphoproliferative skin
      diseases was observed: 87% of LPP and 70% of MF tissue samples tested positive
      for HHV-8 DNA from ORF 26. However, HHV-8 was not detectable in LPP and MF by
      using the immunohistochemical marker LANA. CONCLUSIONS: A virus unambiguously
      associated with KS, HHV-8 was frequently detected at low amounts in LPP and MF
      specimens. However, based on the methods of HHV-8 detection used in this study,
      no conclusion can be drawn on the etiologic and pathogenetic role of HHV-8 in
      these diseases.

PMID- 18711075
TI  - Perifollicular xanthomatosis as the hallmark of axillary Fox-Fordyce disease: an
      evaluation of histopathologic features of 7 cases.
AB  - BACKGROUND: Fox-Fordyce disease (FFD) or apocrine miliaria is a rare condition
      with features that are characteristic clinically but not histopathologically. It
      is traditionally described as a condition that shows infundibular plugging,
      acanthosis, parakeratosis, spongiosis, and a nonspecific infiltrate. The so
      called retention vesicle, which reputedly involves the apocrine duct, is often
      difficult to find. Recently, 4 uncontrolled observations were described
      (infundibular dyskeratotic cells, vacuolar alteration, cornoid lamella-like
      parakeratosis, and perifollicular foamy macrophages). In this study, we evaluated
      both established and new histopathologic criteria for the diagnosis of FFD and
      searched for other meaningful findings. OBSERVATIONS: Most established features
      were observed in both patients with FFD and control patients. All cases occurred
      during 1995 through 2005. No unequivocal retention vesicle was identifiable in
      any case. Infundibular vacuolar change and cornoid lamella-like parakeratosis
      were not corroborated as being diagnostically meaningful. Few dyskeratotic cells
      were seen in some patients with FFD and in control patients. Perifollicular foam
      cells were noted in most patients with FFD but not among control patients. These
      cells expressed CD68 but lacked expression of carcinoembryonic antigen, gross
      cystic disease fluid protein 15, and periodic acid-Schiff with diastase
      digestion. Perifollicular mucin, fibrosis, and mast cells in the infiltrate were
      also observed. CONCLUSIONS: The established histopathologic attributes of FFD are
      nonspecific, and a retention vesicle is difficult to find even in level sections.
      In contrast, perifollicular foam cells are a distinct, relatively consistent, and
      specific feature of FFD. We contend that perifollicular foam cells represent a
      useful hallmark of FFD.

PMID- 18711076
TI  - CD8+ epidermotropic cytotoxic T-cell lymphoma with peripheral blood and central
      nervous system involvement.
AB  - BACKGROUND: Most cutaneous T-cell lymphomas demonstrate a malignant population
      with a CD4(+) phenotype. In rare cases, CD8(+) phenotypes have been described
      based on immunostaining of skin specimens. Although some CD8(+) lymphomas have an
      indolent course, others, such as CD8(+) epidermotropic cytotoxic T-cell
      lymphomas, are typically more aggressive. To our knowledge, involvement of
      peripheral blood or cerebrospinal fluid with a malignant population of CD8(+)
      cells demonstrated by flow cytometry and T-cell receptor gene rearrangement has
      not been previously described. OBSERVATIONS: We describe a patient with a CD8(+)
      cutaneous T-cell lymphoma with an initially indolent course and early stage
      diagnosed on the basis of a skin biopsy specimen. However, when flow cytometry
      was performed looking specifically at CD8(+)/CD4(-) cells in the peripheral blood
      and cerebrospinal fluid, a malignant population of CD8(+)/CD4(-)/CD26(-)/CD7(-)
      cells was discovered. CONCLUSIONS: It is important for prognosis and treatment to
      be able to identify CD8(+) epidermotropic cytotoxic T-cell lymphoma and separate
      it from other relatively indolent CD8(+) lymphomas. Furthermore, detection of an
      abnormal CD8(+)/CD26(-)/CD7(-) T-cell population within the peripheral blood has
      important prognostic and therapeutic implications. The use of flow cytometry
      looking for abnormal CD8(+) populations in the peripheral blood or cerebrospinal
      fluid can assist with this critical information.

PMID- 18711077
TI  - The ringlike pattern in vulvar melanosis: a new dermoscopic clue for diagnosis.
AB  - BACKGROUND: Vulvar melanosis is a benign pigmented lesion that may clinically
      mimic melanoma. Whereas the dermoscopic features of other pigmented skin lesions
      have been extensively described, little is known about vulvar melanosis.
      OBSERVATIONS: A retrospective dermoscopic study was conducted on 87 lesions with
      histopathologically proved melanosis. We describe and define, for the first time
      to our knowledge, a ringlike pattern, found in 28 of 87 melanotic lesions (32%),
      characterized by multiple round to oval structures, white to tan, with dark
      brown, well-defined regular borders. The structureless and globularlike patterns
      were observed in 18 of 87 lesions (21%), the parallel pattern in 15 (17%), and
      the cobblestonelike and reticularlike patterns in 4 (5%). A significant
      association was found between the distribution of multifocal lesions showing a
      ringlike vs a nonringlike pattern (82% vs 52%; P = .008), whereas a weak
      association was found between anatomical site and the different patterns (P =
      .55). The ringlike pattern was frequently combined with multifocality and
      simultaneous occurrence at the labia majora and the labia minora. CONCLUSION:
      Dermoscopy can be useful for the clinical detection of vulvar melanosis, and the
      ringlike pattern may represent a new dermoscopic clue for the diagnosis of this
      lesion.

PMID- 18711078
TI  - Integrating patient preferences with health utilities: a variation on health
      related quality of life.

PMID- 18711079
TI  - Thoughts on implants and contact allergy.

PMID- 18711080
TI  - UV light abuse as a substance-related disorder: clinical implications.

PMID- 18711081
TI  - Leopold Mozart and the first description of erythema nodosum.

PMID- 18711082
TI  - Red annular plaque on the dorsum of the foot.

PMID- 18711083
TI  - Nodule on the toe after traveling to Africa.

PMID- 18711084
TI  - Innumerable filiform papules.

PMID- 18711085
TI  - Painful verrucous plaque on the right index finger.

PMID- 18711086
TI  - New contrast stain for the rapid diagnosis of pityriasis versicolor.

PMID- 18711087
TI  - Late cutaneous manifestations 14 to 20 years after wartime exposure to sulfur
      mustard gas: a long-term investigation.

PMID- 18711088
TI  - Quality of life and disease severity in a cutaneous lupus erythematosus pilot
      study.

PMID- 18711089
TI  - Characteristics of patients with universal vitiligo and health-related quality of
      life.

PMID- 18711090
TI  - Scalp psoriasis: a paradigm of "switch-on" mechanism to anagen hair growth?

PMID- 18711091
TI  - Eczematoid graft-vs-host disease.

PMID- 18711092
TI  - The role of narrowband UV-B plus alefacept combination therapy in the treatment
      of psoriasis.

PMID- 18711093
TI  - Panton-Valentine leukocidin, exfoliative toxins, and skin infections.

PMID- 18711094
TI  - The use of patch tests in determining hypersensitivity to etanercept and
      infliximab.

PMID- 18711095
TI  - A pigmented, hemorrhagic genital wart: clinical, dermoscopic, and histopathologic
      features.

PMID- 18711096
TI  - Successful treatment of Darier disease with the flashlamp-pumped pulsed-dye
      laser.

PMID- 18711097
TI  - Therapeutic effect of argatroban on rheumatoid vasculitis with
      antiphosphatidylserine-prothrombin complex antibody.

PMID- 18711098
TI  - Neuroma formation and toe amputation resulting from stonefish envenomation.

PMID- 18711099
TI  - Pleomorphic adenoma of the soft palate.

PMID- 18711100
TI  - Extensive nodular secondary syphilis with prozone phenomenon.

PMID- 18711101
TI  - Palmar-plantar erythrodysesthesia caused by mercaptopurine and mesalamine.

PMID- 18711102
TI  - Palmar-plantar erythrodysesthesia secondary to sunitinib treatment resulting in
      necrotic foot syndrome aggravated by background diabetic vascular disease.

PMID- 18711103
TI  - Dermoscopy of trichostasis spinulosa.

PMID- 18711104
TI  - Clinical reasoning: A 51-year-old woman with syncopal episodes and multiple
      cranial neuropathies.

PMID- 18711106
TI  - Yet another spinocerebellar ataxia: the saga continues.

PMID- 18711107
TI  - Maintenance of certification: ready or not, here it comes.

PMID- 18711108
TI  - Chronic migraine in the population: burden, diagnosis, and satisfaction with
      treatment.
AB  - OBJECTIVE: To evaluate the disability profile and patterns of treatment and
      health care use for chronic migraine (CM) in the general population, in contrast
      to episodic migraine. METHODS: We identified 24,000 headache sufferers, drawn
      from more than 165,000 individuals representative of the US population. This
      sample has been followed up with annual surveys using validated questionnaires
      for the diagnosis of episodic migraine and CM. As a part of the survey, subjects
      were asked to report the specific medications currently used for their most
      severe headaches, as well as level of satisfaction with treatment. RESULTS: Our
      sample consisted of 520 individuals with CM and 9,424 with episodic migraine.
      Over a 3-month period, more than half of the individuals with CM missed at least
      5 days of household work, compared with 24.3% of those with episodic migraine (p
      < 0.001). Reduced productivity in household work for at least 5 days over 3
      months was reported by 58.1% and 18.2% (p < 0.001); at least 5 days of missed
      family activities was reported by 36.9% and 9.5% (p < 0.001). The majority of the
      CM sufferers (87.6%) had previously sought care to discuss their headaches with a
      health professional. Migraine-specific acute treatments were used by 31.6% of
      respondents with CM and 24.8% with episodic migraine. Around 48% of the
      individuals with CM were satisfied with their acute therapies. Just 33.3% of
      those with CM were currently using preventive medications. CONCLUSION: Chronic
      migraine (CM) is more disabling than episodic migraine in the population.
      Although most individuals with CM sought medical care for this disorder, the
      majority did not receive specific acute or preventive medications.

PMID- 18711109
TI  - Penetrance of LGI1 mutations in autosomal dominant partial epilepsy with auditory
      features.
AB  - BACKGROUND: Assessment of the penetrance of disease-causing mutations is
      extremely important for developing clinical applications of gene discovery, such
      as genetic testing and counseling. Mutations in the leucine-rich, glioma
      inactivated 1 gene (LGI1) have been identified in about 50% of families with
      autosomal dominant partial epilepsy with auditory features (ADPEAF), but
      estimates of LGI1 mutation penetrance have ranged widely, from 50 to 85%. The
      current study aimed to provide a more precise estimate of LGI1 mutation
      penetrance. METHODS: We analyzed data from all 24 previously published ADPEAF
      families with mutations in LGI1. To estimate penetrance, we used the information
      from the published pedigree figures to determine the proportion of obligate
      carriers who were affected. We assessed whether penetrance was associated with
      the total number of affected individuals in each family, or mutation type
      (truncating or missense) or location within the gene. We also compared penetrance
      in males and females, and among different generations within the families.
      RESULTS: Overall penetrance was 67% (95% CI 55-77%), and did not vary according
      to mutation type or location within the gene. Penetrance was greater in families
      with more affected individuals, but this trend was not significant. Penetrance
      did not differ by gender but increased with advancing generation, probably
      because of limited information about early generations. CONCLUSIONS: Our results
      suggest that about two-thirds of individuals who inherit a mutation in LGI1 will
      develop epilepsy. This probably overestimates the true penetrance in the
      population because it is based on data from families containing multiple affected
      individuals.

PMID- 18711110
TI  - Treating obstructive sleep apnea in adults with epilepsy: a randomized pilot
      trial.
AB  - OBJECTIVE: Small uncontrolled series suggest that treatment of obstructive sleep
      apnea (OSA) in patients with epilepsy may improve seizure control. Prior to
      conducting a definitive randomized controlled trial, we addressed critical design
      issues in a pilot study. METHODS: We identified a cohort of adult patients with
      medically refractory epilepsy and coexisting OSA, documented by polysomnography
      (PSG). After an 8-week baseline period, subjects with OSA were randomized to
      therapeutic or sham continuous positive airway pressure (CPAP) for 10 weeks.
      Subjects maintained seizure calendars and antiepileptic drug dosages were held
      constant. RESULTS: Sixty-eight subjects with suspected OSA were enrolled and 35
      subjects randomized to therapeutic CPAP (22 subjects) or sham (13 subjects) CPAP.
      Male gender and an elevated sleep apnea questionnaire score were predictive of
      OSA on PSG. Nineteen subjects in the therapeutic group and all 13 subjects in the
      sham group completed the trial. Baseline apnea-hypopnea index (AHI) and CPAP
      adherence were comparable between groups. A significant reduction in AHI was
      observed in the therapeutic CPAP group as compared to the sham group. Subjects,
      study coordinators, and principal investigators were unable to predict treatment
      allocation. CONCLUSIONS: This pilot study provided critical information related
      to study design and feasibility for planning a comprehensive trial to test the
      hypothesis that treating obstructive sleep apnea in patients with epilepsy
      improves seizure control.

PMID- 18711111
TI  - Drowning in people with epilepsy: how great is the risk?
AB  - BACKGROUND: People with epilepsy are known to be at increased risk of death by
      drowning but there are few data available regarding the size of the risk. We
      aimed to quantify the risk using meta-analysis. METHODS: A literature search
      identified 51 cohorts of people with epilepsy in whom the number of deaths by
      drowning in people with epilepsy and the number of person-years at risk could be
      estimated. Population data were taken from the WHO Statistical Information
      Service or from the UK Office for National Statistics where available.
      Standardized mortality ratios (SMRs) with 95% CIs were calculated for each
      cohort, for groups of cohorts, and for the total population. Additionally, an SMR
      for drowning in people with epilepsy in England and Wales (1999-2000) was
      calculated using National Registries. RESULTS: Eighty-eight drowning deaths were
      observed compared with 4.70 expected, giving an SMR of 18.7 (95% CI 15.0 to
      23.1). Compared with community-based incident studies (SMR 5.4), the SMR was
      significantly raised in prevalent epilepsy (SMR 18.0), in people with epilepsy
      and learning disability (SMR 25.7), in those in institutional care (SMR 96.9),
      and in those who had a temporal lobe excision (SMR 41.1). The SMR for people with
      epilepsy in England and Wales was 15.3. CONCLUSION: The risk of drowning in
      people with epilepsy is raised 15- to 19-fold compared with people in the general
      population. It is important that people with epilepsy and their carers be
      informed of these risks so that deaths can be prevented.

PMID- 18711112
TI  - Melanocortin 1 receptor genotype, past environmental sun exposure, and risk of
      multiple sclerosis.
AB  - OBJECTIVE: Low past sun exposure, fair skin type, and polymorphisms of the MC1R
      gene have been associated with multiple sclerosis (MS) risk. We aimed to
      investigate the interplay between melanocortin 1 receptor gene variants, red
      hair/fair skin phenotype, and past environmental sun exposure in MS. METHODS:
      Population-based case-control study in Tasmania, Australia, involving 136 cases
      with MS and 272 controls randomly drawn from the community and matched on sex and
      year of birth. Measures included past sun exposure by calendar and questionnaire,
      spectrophotometric skin type, and MC1R genotype, with any MC1R Arg151Cys,
      Arg160Trp, or Asp294His alleles present denoted as red hair color (RHC) variant.
      RESULTS: The association between RHC variant genotype and MS was more evident for
      women (odds ratio 2.02 [1.15-3.54]) than for men (odds ratio 0.65 [0.27-1.57])
      (difference in effect, p = 0.03). The RHC variant genotype was associated with
      behavioral sun avoidance. In addition, increasing summer sun exposure at ages 6
      through 10 years was associated with reduced MS risk among those with no RHC
      variant (p = 0.03), but not among those with RHC variant genotype (p = 0.15;
      difference in effect, p = 0.02). Similar findings were evident for other past sun
      exposure measures and when the sample was restricted to women only. CONCLUSION:
      The interplay between red hair color variant genotype, red hair/fair skin
      phenotype, and multiple sclerosis (MS) is complex. The modification of past sun
      exposure by MC1R genotype provides further support that ultraviolet radiation or
      derivatives such as vitamin D may be causally related to a reduced MS risk.

PMID- 18711113
TI  - Unilateral INO is associated with ocular tilt reaction in pontomesencephalic
      lesions: INO plus.
AB  - OBJECTIVE: Correlation of internuclear ophthalmoplegia (INO) with components of
      the ocular tilt reaction (OTR) in order to localize graviceptive (specifically
      otolithic) pathways in the brainstem. METHODS: We retrospectively analyzed data
      of 120 patients with INO (87 unilateral [9 of whom had one-and-a-half syndrome],
      33 bilateral) for OTR (subjective visual vertical [SVV], ocular torsion, skew
      deviation) to localize causative brainstem lesions in MRI. RESULTS: Unilateral
      INO was accompanied by at least one component of OTR: SVV tilt in 96%, ocular
      torsion in 79%, and skew deviation in 50%. All components were directed to the
      contralesional side. Contralateral OTR occurred in 89% of patients with one-and-a
      half syndrome. Only 9% of patients with bilateral INO exhibited OTR. MRI showed
      distinct lesions in 68%, which almost exclusively projected onto the
      pontomesencephalic medial longitudinal fascicle (96%). Follow-up measurements
      revealed SVV and ocular torsion normalized faster than the adduction deficit in
      INO. CONCLUSIONS: First, unilateral internuclear ophthalmoplegia (INO) is
      regularly associated with contraversive ocular tilt reaction (OTR): INO plus.
      Thus, graviceptive pathways join the medial longitudinal fascicle after crossing
      between the vestibular and abducens nuclei. Second, the different time course and
      degree of recovery of OTR components and INO signs can be explained by the
      hypothesis that vestibular tone imbalance is compensated by central vestibular
      adaptation mechanisms (probably driven mainly by cerebellar-vestibular
      projections), whereas impaired adduction is less susceptible to compensation
      according to Hering's law and can only be overcome by lesion repair. Third,
      bilateral INO is seldom associated with OTR, confirming that bilateral impairment
      of graviceptive pathways does not cause imbalance in roll plane.

PMID- 18711114
TI  - Suprachiasmatic nucleus and melatonin: reciprocal interactions and clinical
      correlations.

PMID- 18711115
TI  - Invited Article: Maintenance of certification: the next phase in assessing and
      improving physician performance.

PMID- 18711116
TI  - Vertebral osteomyelitis complicating pneumococcal meningitis.

PMID- 18711117
TI  - Perfusion alterna in Takayasu arteritis.

PMID- 18711118
TI  - How effective are disease-modifying drugs in delaying progression in relapsing
      onset ms?

PMID- 18711119
TI  - Whose side are you on?

PMID- 18711120
TI  - Arthritis and pneumonitis produced by the same T cell clones from mice with
      spontaneous autoimmune arthritis.
AB  - SKG mice, a newly established model of rheumatoid arthritis (RA), spontaneously
      develop autoimmune arthritis accompanying extra-articular manifestations, such as
      interstitial pneumonitis. To examine possible roles of T cells for mediating this
      systemic autoimmunity, we generated T cell clones from arthritic joints of SKG
      mice. Two distinct CD8(+) clones were established and both showed in vitro
      autoreactivity by killing syngeneic synovial cells and a variety of MHC-matched
      cell lines. Transfer of each clone to histocompatible athymic nude mice elicited
      joint swelling and histologically evident synovitis accompanying the destruction
      of adjacent cartilage and bone. Notably, the transfer also produced diffuse
      severe interstitial pneumonitis. Clone-specific TCR gene messages in the inflamed
      joints and lungs of the recipients gradually diminished, becoming hardly
      detectable in 6-11 months; yet, arthritis and pneumonitis continued to progress.
      Thus, the same CD8(+) T cell clones from arthritic lesions of SKG mice can elicit
      both synovitis and pneumonitis, which chronically progress and apparently become
      less T cell dependent in a later phase. The results provide clues to our
      understanding of how self-reactive T cells cause both articular and extra
      articular lesions in RA as a systemic autoimmune disease.

PMID- 18711121
TI  - Promoter of a cotton fibre MYB gene functional in trichomes of Arabidopsis and
      glandular trichomes of tobacco.
AB  - Cotton fibres are unicellular seed trichomes. Our previous study suggested that
      the cotton R2R3 MYB transcript factor GaMYB2 is a functional homologue of the
      Arabidopsis trichome regulator GLABRA1 (GL1). Here, the GaMYB2 promoter activity
      is reported in cotton (Gossypium hirsutum), tobacco (Nicotiana tabacum), and
      Arabidopsis plants. A 2062 bp promoter of GaMYB2 was isolated from G. arboreum,
      and fused to a beta-glucuronidase (GUS) reporter gene. In cotton, the GaMYB2
      promoter exhibited activities in developing fibre cells and trichomes of other
      aerial organs, including leaves, stems and bracts. In Arabidopsis the promoter
      was specific to trichomes. Different from Arabidopsis and cotton that have
      unicellular non-glandular simple trichomes, tobacco plants contain more than one
      type of trichome, including multicellular simple and glandular secreting
      trichomes (GSTs). Interestingly, in tobacco plants the GaMYB2 promoter directed
      GUS expression exclusively in glandular cells of GSTs. A series of 5'-deletions
      revealed that a 360 bp fragment upstream to the translation initiation codon was
      sufficient to drive gene expression. A putative cis-element of the T/G-box was
      located at -233 to -214; a yeast one-hybrid assay showed that Arabidopsis bHLH
      protein GLABRA3 (GL3), also a trichome regulator, and GhDEL65, a GL3-like cotton
      protein, had high binding activities to the T/G-box motif. Overexpression of GL3
      or GhDEL65 enhanced the GaMYB2 promoter activity in transgenic Arabidopsis
      plants. A comparison of GaMYB2 promoter specificities in trichomes of different
      plant species with different types of trichomes provides a tool for further
      dissection of plant trichome structure and development.

PMID- 18711122
TI  - Interactions between polycyclic aromatic hydrocarbons in binary mixtures: effects
      on gene expression and DNA adduct formation in precision-cut rat liver slices.
AB  - Although exposure to polycyclic aromatic hydrocarbons (PAHs) occurs mostly
      through mixtures, hazard and risk assessment are mostly based on the effects
      caused by individual compounds. The objective of the current study was to
      investigate whether interactions between PAHs occur, focusing on gene expression
      (as measured by cDNA microarrays) and DNA adduct formation. The effects of
      benzo[a]pyrene or dibenzo[a,h]anthracene (DB[a,h]A) alone and in binary mixtures
      with another PAH (DB[a,h]A, benzo[b]fluoranthene, fluoranthene or
      dibenzo[a,l]pyrene) were investigated using precision-cut rat liver slices. All
      compounds significantly modulated the expression of several genes, but overlap
      between genes affected by the mixture and by the individual compounds was
      relatively small. All mixtures showed an antagonistic response on total gene
      expression profiles. Moreover, at the level of individual genes, mostly
      antagonism was evident, with additivity and synergism observed for only a few
      genes. As far as DNA adduct formation is concerned, the binary mixtures generally
      caused antagonism. The effects in liver slices suggest a lower carcinogenic
      potency of PAH mixtures than estimated based on additivity of individual
      compounds.

PMID- 18711123
TI  - Ecological changes in Miocene mammalian record show impact of prolonged climatic
      forcing.
AB  - Geohistorical records reveal the long-term impacts of climate change on ecosystem
      structure. A 5-myr record of mammalian faunas from floodplain ecosystems of South
      Asia shows substantial change in species richness and ecological structure in
      relation to vegetation change as documented by stable isotopes of C and O from
      paleosols. Between 8.5 and 6.0 Ma, C(4) savannah replaced C(3) forest and
      woodland. Isotopic historical trends for 27 mammalian herbivore species, in
      combination with ecomorphological data from teeth, show three patterns of
      response. Most forest frugivores and browsers maintained their dietary habits and
      disappeared. Other herbivores altered their dietary habits to include increasing
      amounts of C(4) plants and persisted for >1 myr during the vegetation transition.
      The few lineages that persisted through the vegetation transition show isotopic
      enrichment of delta(13)C values over time. These results are evidence for long
      term climatic forcing of vegetation structure and mammalian ecological diversity
      at the subcontinental scale.

PMID- 18711124
TI  - TSLP acts on infiltrating effector T cells to drive allergic skin inflammation.
AB  - Thymic stromal lymphopoietin (TSLP) is a cytokine expressed by epithelial cells,
      including keratinocytes, and is important in allergic inflammation. Allergic skin
      inflammation elicited by epicutaneous immunization of mice with ovalbumin (OVA),
      a potential model of atopic dermatitis, was severely impaired in TSLPR(-/-) mice,
      as evidenced by decreased infiltration of eosinophils and decreased local
      expression of T helper 2 (Th2) cytokines. However, secretion of Th2 cytokines by
      splenocytes from epicutaneous sensitized TSLPR(-/-) mice in response to OVA was
      normal. Skin dendritic cells from TSLPR(-/-) mice were normal in their ability to
      migrate to draining lymph nodes, express activation markers, and induce
      proliferation and Th2 cytokine production by naive T cells. CD4(+) T cells from
      TSLPR(-/-) mice expressed the skin homing receptor E-selectin ligand normally,
      and homed to the skin normally, but failed to transfer allergic skin inflammation
      to WT recipients. TSLP enhanced Th2 cytokine secretion in vitro by targeting
      TSLPR on antigen specific T cells. Intradermal injection of anti-TSLP blocked the
      development of allergic skin inflammation after cutaneous antigen challenge of
      OVA immunized WT mice. These findings suggest that TSLP is essential for antigen
      driven Th2 cytokine secretion by skin infiltrating effector T cells and could be
      a therapeutic target in allergic skin inflammation.

PMID- 18711125
TI  - Fluctuating asymmetry and preferences for sex-typical bodily characteristics.
AB  - Body size and shape seem to have been sexually selected in a variety of species,
      including humans, but little is known about what attractive bodies signal about
      underlying genotypic or phenotypic quality. A widely used indicator of phenotypic
      quality in evolutionary analyses is degree of symmetry (i.e., fluctuating
      asymmetry, FA) because it is a marker of developmental stability, which is
      defined as an organism's ability to develop toward an adaptive end-point despite
      perturbations during its ontogeny. Here we sought to establish whether attractive
      bodies signal low FA to observers, and, if so, which aspects of attractive bodies
      are most predictive of lower FA. We used a 3D optical body scanner to measure FA
      and to isolate size and shape characteristics in a sample of 77 individuals (40
      males and 37 females). From the 3D body scan data, 360 degrees videos were
      created that separated body shape from other aspects of visual appearance (e.g.,
      skin color and facial features). These videos then were presented to 87
      evaluators for attractiveness ratings. We found strong negative correlations
      between FA and bodily attractiveness in both sexes. Further, sex-typical body
      size and shape characteristics were rated as attractive and correlated negatively
      with FA. Finally, geometric morphometric analysis of joint configurations
      revealed that sex-typical joint configurations were associated with both
      perceived attractiveness and lower FA for male but not for female bodies. In sum,
      body size and shape seem to show evidence of sexual selection and indicate
      important information about the phenotypic quality of individuals.

PMID- 18711126
TI  - Receptor density balances signal stimulation and attenuation in membrane
      assembled complexes of bacterial chemotaxis signaling proteins.
AB  - All cells possess transmembrane signaling systems that function in the
      environment of the lipid bilayer. In the Escherichia coli chemotaxis pathway, the
      binding of attractants to a two-dimensional array of receptors and signaling
      proteins simultaneously inhibits an associated kinase and stimulates receptor
      methylation--a slower process that restores kinase activity. These two opposing
      effects lead to robust adaptation toward stimuli through a physical mechanism
      that is not understood. Here, we provide evidence of a counterbalancing influence
      exerted by receptor density on kinase stimulation and receptor methylation.
      Receptor signaling complexes were reconstituted over a range of defined surface
      concentrations by using a template-directed assembly method, and the kinase and
      receptor methylation activities were measured. Kinase activity and methylation
      rates were both found to vary significantly with surface concentration--yet in
      opposite ways: samples prepared at high surface densities stimulated kinase
      activity more effectively than low-density samples, whereas lower surface
      densities produced greater methylation rates than higher densities. FRET
      experiments demonstrated that the cooperative change in kinase activity coincided
      with a change in the arrangement of the membrane-associated receptor domains. The
      counterbalancing influence of density on receptor methylation and kinase
      stimulation leads naturally to a model for signal regulation that is compatible
      with the known logic of the E. coli pathway. Density-dependent mechanisms are
      likely to be general and may operate when two or more membrane-related processes
      are influenced differently by the two-dimensional concentration of pathway
      elements.

PMID- 18711127
TI  - Loss of AKAP150 perturbs distinct neuronal processes in mice.
AB  - A-Kinase Anchoring Proteins (AKAPs) ensure the fidelity of second messenger
      signaling events by directing protein kinases and phosphatases toward their
      preferred substrates. AKAP150 brings protein kinase A (PKA), the
      calcium/calmodulin dependent phosphatase PP2B and protein kinase C (PKC) to
      postsynaptic membranes where they facilitate the phosphorylation dependent
      modulation of certain ion channels. Immunofluorescence and electrophysiological
      recordings were combined with behavioral analyses to assess whether removal of
      AKAP150 by gene targeting in mice changes the signaling environment to affect
      excitatory and inhibitory neuronal processes. Mislocalization of PKA in AKAP150
      null hippocampal neurons alters the bidirectional modulation of postsynaptic AMPA
      receptors with concomitant changes in synaptic transmission and memory retention.
      AKAP150 null mice also exhibit deficits in motor coordination and strength that
      are consistent with a role for the anchoring protein in the cerebellum. Loss of
      AKAP150 in sympathetic cervical ganglion (SCG) neurons reduces muscarinic
      suppression of inhibitory M currents and provides these animals with a measure of
      resistance to seizures induced by the non-selective muscarinic agonist
      pilocarpine. These studies argue that distinct AKAP150-enzyme complexes regulate
      context-dependent neuronal signaling events in vivo.

PMID- 18711128
TI  - Metal-organic frameworks with high capacity and selectivity for harmful gases.
AB  - Benchmarks have been established for the performance of six metal-organic
      frameworks (MOFs) and isoreticular MOFs (IRMOFs, which have the same underlying
      topology as MOF-5), MOF-5, IRMOF-3, MOF-74, MOF-177, MOF-199, and IRMOF-62, as
      selective adsorbents for eight harmful gases: sulfur dioxide, ammonia, chlorine,
      tetrahydrothiophene, benzene, dichloromethane, ethylene oxide, and carbon
      monoxide. Kinetic breakthrough measurements are used to determine the calculated
      dynamic adsorption capacity of each "benchmark" MOF for each gas. The capacity of
      each MOF is compared to that of a sample of Calgon BPL activated carbon. We find
      that pore functionality plays a dominant role in determining the dynamic
      adsorption performance of MOFs. MOFs featuring reactive functionality outperform
      BPL carbon in all but one case and exhibit high dynamic adsorption capacities up
      to 35% by weight.

PMID- 18711129
TI  - Allopolyploid speciation in Persicaria (Polygonaceae): insights from a low-copy
      nuclear region.
AB  - Using a low-copy nuclear gene region (LEAFY second intron) we show multiple
      instances of allopolyploid speciation in Persicaria (Polygonaceae), which
      includes many important weeds. Fifteen species seem to be allopolyploids, which
      is higher than the number found in previous comparisons of chloroplast DNA and
      nuclear ribosomal internal transcribed spacer (nrITS) phylogenies. This
      underestimation of the extent of allopolyploidy is due in at least three cases to
      homogenization of nrITS toward the maternal lineage. One of the diploid species,
      P. lapathifolia, has been involved in at least six cases of allopolyploid
      speciation. Of the diploids, this species is the most widespread geographically
      and ecologically and also bears more numerous and conspicuous flowers,
      illustrating ecologic factors that may influence hybridization frequency. With a
      few exceptions, especially the narrowly endemic hexaploid, P. puritanorum, the
      allopolyploid species also are widespread, plastic, ecological generalists.
      Hybridization events fostered by human introductions may be fueling the
      production of new species that have the potential to become aggressive weeds.

PMID- 18711130
TI  - The origin recognition complex is dispensable for endoreplication in Drosophila.
AB  - The origin recognition complex (ORC) is an essential component of the
      prereplication complex (pre-RC) in mitotic cell cycles. The role of ORC as a
      foundation to assemble the pre-RC is conserved from yeast to human. Furthermore,
      in metazoans ORC plays a key role in determining the timing of replication
      initiation and origin usage. In this report we have produced and analyzed a
      Drosophila orc1 allele to investigate the roles of ORC1 in three different modes
      of DNA replication during development. As expected, ORC1 is essential for mitotic
      replication and proliferation in brains and imaginal discs, as well as for gene
      amplification in ovarian follicle cells. Surprisingly, however, ORC1 is not
      required for endoreplication. Decreased cell number in orc1 mutant salivary
      glands is consistent with the idea that undetectable levels of maternal ORC1
      during embryogenesis fail to support further proliferation. Nevertheless, these
      cells begin endoreplicating normally and reach a final ploidy of >1000C in the
      absence of zygotic synthesis of ORC1. The dispensability of ORC is further
      supported by an examination of other ORC members, whereas Double-parked
      protein/Cdt1 and minichromosome maintenance proteins are apparently essential for
      endoreplication, implying that some aspects of initiation are shared among the
      three modes of DNA replication. This study provides insight into the physiologic
      roles of ORC during metazoan development and proposes that DNA replication
      initiation is governed differently in mitotic and endocycles.

PMID- 18711131
TI  - B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive
      impairment in mice.
AB  - In older adults, mildly elevated plasma total homocysteine (hyperhomocysteinemia)
      is associated with increased risk of cognitive impairment, cerebrovascular
      disease, and Alzheimer's disease, but it is uncertain whether this is due to
      underlying metabolic, neurotoxic, or vascular processes. We report here that
      feeding male C57BL6/J mice a B-vitamin-deficient diet for 10 weeks induced
      hyperhomocysteinemia, significantly impaired spatial learning and memory, and
      caused a significant rarefaction of hippocampal microvasculature without
      concomitant gliosis and neurodegeneration. Total hippocampal capillary length was
      inversely correlated with Morris water maze escape latencies (r = -0.757, P <
      0.001), and with plasma total homocysteine (r = -0.631, P = 0.007). Feeding mice
      a methionine-rich diet produced similar but less pronounced effects. Our findings
      suggest that cerebral microvascular rarefaction can cause cognitive dysfunction
      in the absence of or preceding neurodegeneration. Similar microvascular changes
      may mediate the association of hyperhomocysteinemia with human age-related
      cognitive decline.

PMID- 18711132
TI  - SEL1L nucleates a protein complex required for dislocation of misfolded
      glycoproteins.
AB  - Membrane and secretory proteins that fail to pass quality control in the
      endoplasmic reticulum are discharged into the cytosol and degraded by the
      proteasome. Many of the mammalian components involved in this process remain to
      be identified. We performed a biochemical search for proteins that interact with
      SEL1L, a protein that is part of the mammalian HRD1 ligase complex and involved
      in substrate recognition. SEL1L is crucial for dislocation of Class I major
      histocompatibility complex heavy chains by the human cytomegalovirus US11
      protein. We identified AUP1, UBXD8, UBC6e, and OS9 as functionally important
      components of this degradation complex in mammalian cells, as confirmed by
      mutagenesis and dominant negative versions of these proteins.

PMID- 18711133
TI  - Discovering interactions among BRCA1 and other candidate genes associated with
      sporadic breast cancer.
AB  - Analysis of a subset of case-control sporadic breast cancer data, [from the
      National Cancer Institute's Cancer Genetic Markers of Susceptibility (CGEMS)
      initiative], focusing on 18 breast cancer-related genes with 304 SNPs, indicates
      that there are many interesting interactions that form two- and three-way
      networks in which BRCA1 plays a dominant and central role. The apparent
      interactions of BRCA1 with many other genes suggests the conjecture that BRCA1
      serves as a protective gene and that some mutations in it or in related genes may
      prevent it from carrying out this protective function even if the patients are
      not carriers of known cancer-predisposing BRCA1 mutations. The method of analysis
      features the evaluation of the effect of a gene by averaging the effects of the
      SNPs covered by that gene. Marginal methods that test one gene at a time fail to
      show any effect. That may be related to the fact that each of these 18 genes adds
      very little to the risk of cancer. Analysis that relates the ratio of
      interactions to the maximum of the first-order effects discovers significant gene
      pairs and triplets.

PMID- 18711134
TI  - Timing of initial arrival at the breeding site predicts age at first reproduction
      in a long-lived migratory bird.
AB  - In long-lived vertebrates, individuals generally visit potential breeding areas
      or populations during one or more seasons before reproducing for the first time.
      During these years of prospecting, they select a future breeding site, colony, or
      mate and improve various skills and their physical condition to meet the
      requirements of reproduction. One precondition of successful reproduction is
      arrival in time on the breeding grounds. Here, we study the intricate links among
      the date of initial spring arrival, body mass, sex, and the age of first breeding
      in the common tern Sterna hirundo, a long-lived migratory colonial seabird. The
      study is based on a unique, individual-based, long-term dataset of sexed birds,
      marked with transponders, which allow recording their individual arrival, overall
      attendance, and clutch initiation remotely and automatically year by year over
      the entire lifetime at the natal colony site. We show that the seasonal date of
      initial arrival at the breeding grounds predicts the individual age at first
      reproduction, which mostly occurs years later. Late first-time arrivals remain
      delayed birds throughout subsequent years. Our findings reveal that timing of
      arrival at the site of reproduction and timing of reproduction itself are
      coherent parameters of individual quality, which are linked with the prospects of
      the breeding career and may have consequences for fitness.

PMID- 18711135
TI  - Differential vascularization of nematode-induced feeding sites.
AB  - Sedentary nematodes are destructive plant pathogens that cause significant yield
      losses. In the roots of their host plants, cyst nematodes (CNs) and root-knot
      nematodes (RKNs) induce different, highly specialized feeding sites--syncytia or
      giant cells (GCs), respectively--to optimize nutrient uptake. We compared the
      mechanisms by which nutrients are delivered from the model host plant,
      Arabidopsis, to GCs induced by the RKN Meloidogyne incognita or to syncytia
      induced by the CN Heterodera schachtii. From previous work, syncytia were known
      to be symplastically connected to newly formed host phloem composed of sieve
      elements (SEs) and companion cells. Here we studied the formation of
      plasmodesmata (PD) during GC and syncytia development by monitoring a viral
      movement protein that targets branched PD and the development of host phloem
      during GC formation by applying confocal laser scanning microscopy and
      immunocytochemistry. Analyses of plants expressing soluble or membrane-anchored
      green fluorescent protein in their phloem demonstrated symplastic isolation of
      GCs. GCs were found to be embedded in a tissue that consists exclusively of SEs.
      These de novo-formed SEs, contained nuclei and were interconnected by secondary
      PD. A similar interconnection of SEs was observed around syncytia. However, these
      secondary PD were also present at the SE-syncytium interface, demonstrating the
      postulated symplastic connection. Our results show that CNs and RKNs, despite
      their close phylogenetic relatedness, employ fundamentally different strategies
      to withdraw nutrients from host plants.

PMID- 18711136
TI  - Modeling oncogene addiction using RNA interference.
AB  - The clinical efficacy of selective kinase inhibitors suggests that some cancer
      cells may become dependent on a single oncogene for survival. RNAi has been
      increasingly used to understand such "oncogene addiction" and validate new
      therapeutic targets. However, RNAi approaches suffer from significant off-target
      effects that limit their utility. Here, we combine carefully titrated lentiviral
      mediated short hairpin RNA knockdown of the epidermal growth factor receptor
      (EGFR) with heterologous reconstitution by EGFR mutants to rigorously analyze the
      structural features and signaling activities that determine addiction to the
      mutationally activated EGFR in human lung cancer cells. EGFR dependence is
      differentially rescued by distinct EGFR variants and oncogenic mutants, is
      critically dependent on its heterodimerization partner ErbB-3, and surprisingly,
      does not require autophosphorylation sites in the cytoplasmic domain.
      Quantitative "oncogene rescue" analysis allows mechanistic dissection of oncogene
      addiction, and, when broadly applied, may provide functional validation for
      potential therapeutic targets identified through large-scale RNAi screens.

PMID- 18711137
TI  - Mosquitoes smell and avoid the insect repellent DEET.
AB  - The insect repellent DEET is effective against a variety of medically important
      pests, but its mode of action still draws considerable debate. The widely
      accepted hypothesis that DEET interferes with the detection of lactic acid has
      been challenged by demonstrated DEET-induced repellency in the absence of lactic
      acid. The most recent hypothesis suggests that DEET masks or jams the olfactory
      system by attenuating electrophysiological responses to 1-octen-3-ol. Our
      research shows that mosquitoes smell DEET directly and avoid it. We performed
      single-unit recordings from all functional ORNs on the antenna and maxillary
      palps of Culex quinquefasciatus and found an ORN in a short trichoid sensillum
      responding to DEET in a dose-dependent manner. The same ORN responded with higher
      sensitivity to terpenoid compounds. SPME and GC analysis showed that odorants
      were trapped in conventional stimulus cartridges upon addition of a DEET
      impregnated filter paper strip thus leading to the observed reduced
      electrophysiological responses, as reported elsewhere. With a new stimulus
      delivery method releasing equal amounts of 1-octen-3-ol alone or in combination
      with DEET we found no difference in neuronal responses. When applied to human
      skin, DEET altered the chemical profile of emanations by a "fixative" effect that
      may also contribute to repellency. However, the main mode of action is the direct
      detection of DEET as indicated by the evidence that mosquitoes are endowed with
      DEET-detecting ORNs and corroborated by behavioral bioassays. In a sugar-feeding
      assay, both female and male mosquitoes avoided DEET. In addition, mosquitoes
      responding only to physical stimuli avoided DEET.

PMID- 18711138
TI  - Coal burning leaves toxic heavy metal legacy in the Arctic.
AB  - Toxic heavy metals emitted by industrial activities in the midlatitudes are
      transported through the atmosphere and deposited in the polar regions;
      bioconcentration and biomagnification in the food chain mean that even low levels
      of atmospheric deposition may threaten human health and Arctic ecosystems. Little
      is known about sources and long-term trends of most heavy metals before
      approximately 1980, when modern measurements began, although heavy-metal
      pollution in the Arctic was widespread during recent decades. Lacking detailed,
      long-term measurements until now, ecologists, health researchers, and policy
      makers generally have assumed that contamination was highest during the 1960s and
      1970s peak of industrial activity in North America and Europe. We present
      continuous 1772-2003 monthly and annually averaged deposition records for highly
      toxic thallium, cadmium, and lead from a Greenland ice core showing that
      atmospheric deposition was much higher than expected in the early 20th century,
      with tenfold increases from preindustrial levels by the early 1900s that were two
      to five times higher than during recent decades. Tracer measurements indicate
      that coal burning in North America and Europe was the likely source of these
      metals in the Arctic after 1860. Although these results show that heavy-metal
      pollution in the North Atlantic sector of the Arctic is substantially lower today
      than a century ago, contamination of other sectors may be increasing because of
      the rapid coal-driven growth of Asian economies.

PMID- 18711139
TI  - Exceptional longevity does not result in excessive levels of disability.
AB  - Late-life loss of independence in daily living is a central concern for the aging
      individual and for society. The implications of increased survival to advanced
      age may be different at the population level than at the individual level. Here
      we used a longitudinal multi-assessment survey of the entire Danish 1905 cohort
      from 1998 to 2005 to assess the loss of physical and cognitive independence in
      the age range of 92 to 100 years. Multiple functional outcomes were studied,
      including independence, which was defined as being able to perform basic
      activities of daily living without assistance from other persons and having a
      MiniMental State Examination (MMSE) score of 23 or higher. In the aggregate, the
      1905 cohort had only a modest decline in the proportion of independent
      individuals at the 4 assessments between age 92 and 100 years: 39%, 36%, 32%, and
      33%, with a difference between first and last assessment of 6% [95% confidence
      interval (CI), -1-14%]. For participants who survived until 2005, however, the
      prevalence of independence was reduced by more than a factor of 2, from 70% in
      1998 to 33% in 2005 (difference, 37%; 95% CI, 28-46%). Similar results were
      obtained for the other functional outcomes. Analyses of missing data resulting
      from nonresponse and death suggest that the discrepancy between the population
      trajectory and the individual trajectory is caused by increased mortality among
      dependent individuals. For the individual, long life brings an increasing risk of
      loss of independence. For society, mortality reductions are not expected to
      result in exceptional levels of disability in cohorts of the very old.

PMID- 18711140
TI  - Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor
      cell characteristics.
AB  - Ovulation induces cyclic rupture and regenerative repair of the ovarian coelomic
      epithelium. This process of repeated disruption and repair accompanied by complex
      remodeling typifies a somatic stem/progenitor cell-mediated process. Using BrdU
      incorporation and doxycycline inducible histone2B-green fluorescent protein pulse
      chase techniques, we identify a label-retaining cell population in the coelomic
      epithelium of the adult mouse ovary as candidate somatic stem/progenitor cells.
      The identified population exhibits quiescence with asymmetric label retention,
      functional response to estrous cycling in vivo by proliferation, enhanced growth
      characteristics by in vitro colony formation, and cytoprotective mechanisms by
      enrichment for the side population. Together, these characteristics identify the
      label-retaining cell population as a candidate for the putative somatic
      stem/progenitor cells of the coelomic epithelium of the mouse ovary.

PMID- 18711141
TI  - Oncogenic bystander radiation effects in Patched heterozygous mouse cerebellum.
AB  - The central dogma of radiation biology, that biological effects of ionizing
      radiation are a direct consequence of DNA damage occurring in irradiated cells,
      has been challenged by observations that genetic/epigenetic changes occur in
      unexposed "bystander cells" neighboring directly-hit cells, due to cell-to-cell
      communication or soluble factors released by irradiated cells. To date, the vast
      majority of these effects are described in cell-culture systems, while in vivo
      validation and assessment of biological consequences within an organism remain
      uncertain. Here, we describe the neonatal mouse cerebellum as an accurate in vivo
      model to detect, quantify, and mechanistically dissect radiation-bystander
      responses. DNA double-strand breaks and apoptotic cell death were induced in
      bystander cerebellum in vivo. Accompanying these genetic events, we report
      bystander-related tumor induction in cerebellum of radiosensitive Patched-1
      (Ptch1) heterozygous mice after x-ray exposure of the remainder of the body. We
      further show that genetic damage is a critical component of in vivo oncogenic
      bystander responses, and provide evidence supporting the role of gap-junctional
      intercellular communication (GJIC) in transmission of bystander signals in the
      central nervous system (CNS). These results represent the first proof-of
      principle that bystander effects are factual in vivo events with carcinogenic
      potential, and implicate the need for re-evaluation of approaches currently used
      to estimate radiation-associated health risks.

PMID- 18711142
TI  - Supralinear potentiation of NR1/NR3A excitatory glycine receptors by Zn2+ and NR1
      antagonist.
AB  - Coassembly of the glycine-binding NMDA receptor subunits NR1 and NR3A results in
      excitatory glycine receptors of low efficacy. Here, we report that micromolar
      concentrations of the divalent cation Zn(2+) produce a 10-fold potentiation of
      NR1/NR3A receptor responses, which resembles that seen upon antagonizing glycine
      binding to the NR1 subunit. Coapplication of both Zn(2+) and NR1 antagonist
      caused a supralinear potentiation, resulting in a >120-fold increase of glycine
      activated currents. At concentrations >50 microM, Zn(2+) alone generated receptor
      currents with similar efficacy as glycine, implying that NR1/NR3A receptors can
      be activated by different agonists. Point mutations in the NR1 and NR3A glycine
      binding sites revealed that both the potentiating and agonistic effects of Zn(2+)
      are mediated by the ligand-binding domain of the NR1 subunit. In conclusion,
      Zn(2+) acts as a potent positive modulator and agonist at the NR1 subunit of
      NR1/NR3A receptors. Our results suggest that this unconventional member of the
      NMDA receptor family may in vivo be gated by the combined action of glycine and
      Zn(2+) or a yet unknown second ligand.

PMID- 18711143
TI  - Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in
      the nucleus of cardiomyocytes.
AB  - G protein-coupled receptor (GPCR) kinases (GRKs) are critical regulators of
      cellular signaling and function. In cardiomyocytes, GRK2 and GRK5 are two GRKs
      important for myocardial regulation, and both have been shown to be up-regulated
      in the dysfunctional heart. We report that increased levels and activity of GRK5
      in failing myocardium may have unique significance due to its nuclear
      localization, a property not shared by GRK2. We find that transgenic mice with
      elevated cardiac GRK5 levels have exaggerated hypertrophy and early heart failure
      compared with control mice after pressure overload. This pathology is not present
      in cardiac GRK2-overexpressing mice or in mice with overexpression of a mutant
      GRK5 that is excluded from the nucleus. Nuclear accumulation of GRK5 is enhanced
      in myocytes after aortic banding in vivo and in vitro in myocytes after increased
      G alpha q activity, the trigger for pressure-overload hypertrophy. GRK5 enhances
      activation of MEF2 in concert with Gq signals, demonstrating that nuclear
      localized GRK5 regulates gene transcription via a pathway critically linked to
      myocardial hypertrophy. Mechanistically, we show that this is due to GRK5 acting,
      in a non-GPCR manner, as a class II histone deacetylase (HDAC) kinase because it
      can associate with and phosphorylate the myocyte enhancer factor-2 repressor,
      HDAC5. Moreover, significant HDAC activity can be found with GRK5 in the heart.
      Our data show that GRK5 is a nuclear HDAC kinase that plays a key role in
      maladaptive cardiac hypertrophy apparently independent of any action directly on
      GPCRs.

PMID- 18711144
TI  - Engineered recombinant human paraoxonase 1 (rHuPON1) purified from Escherichia
      coli protects against organophosphate poisoning.
AB  - The high-density lipoprotein-associated enzyme paraoxonase 1 (PON1) hydrolyzes
      lactones, aromatic esters, and neurotoxic organophosphorus (OP) compounds,
      including insecticide metabolites and nerve agents. Experiments with mice lacking
      PON1 (PON1(-/-) mice) have established that plasma PON1 protects against
      chlorpyrifos/chlorpyrifos-oxon and diazinon/diazoxon (DZO) exposure but does not
      protect against parathion/paraoxon or nerve agents. The catalytic efficiency of
      PON1 determines whether or not it will protect against a given OP exposure.
      Expression of active recombinant human PON1 (rHuPON1) in Escherichia coli
      provides a system in which PON1 can be engineered to achieve a catalytic
      efficiency sufficient to protect against or treat specific OP exposures. Here, we
      describe the generation of highly purified engineered rHuPON1(K192) that protects
      against DZO exposure when injected into PON1(-/-) mice. The injected rHuPON1 is
      nontoxic, persists in serum for at least 2 days after injection, and provides
      protection against DZO exposures of at least three times the median lethal dose
      value.

PMID- 18711145
TI  - Water-stable organic transistors and their application in chemical and biological
      sensors.
AB  - The development of low-cost, reliable sensors will rely on devices capable of
      converting an analyte binding event to an easily read electrical signal. Organic
      thin-film transistors (OTFTs) are ideal for inexpensive, single-use chemical or
      biological sensors because of their compatibility with flexible, large-area
      substrates, simple processing, and highly tunable active layer materials. We have
      fabricated low-operating voltage OTFTs with a cross-linked polymer gate
      dielectric, which display stable operation under aqueous conditions over >10(4)
      electrical cycles using the p-channel semiconductor 5,5'-bis-(7-dodecyl-9H
      fluoren-2-yl)-2,2'-bithiophene (DDFTTF). OTFT sensors were demonstrated in
      aqueous solutions with concentrations as low as parts per billion for
      trinitrobenzene, methylphosphonic acid, cysteine, and glucose. This work
      demonstrates of reliable OTFT operation in aqueous media, hence opening new
      possibilities of chemical and biological sensing with OTFTs.

PMID- 18711146
TI  - Dynamical reconstruction of the exciton in LiF with inelastic x-ray scattering.
AB  - The absorption of light by materials proceeds through the formation of excitons,
      which are states in which an excited electron is bound to the valence hole it
      vacated. Understanding the structure and dynamics of excitons is important, for
      example, for developing technologies for light-emitting diodes or solar energy
      conversion. However, there has never been an experimental means to study the time
      dependent structure of excitons directly. Here, we use causality-inverted
      inelastic x-ray scattering (IXS) to image the charge-transfer exciton in the
      prototype insulator LiF, with resolutions Delta t = 20.67 as (2.067 x 10(-17) s)
      in time and Delta x = 0.533 A (5.33 x 10(-11) m) in space. Our results show that
      the exciton has a modulated internal structure and is coherently delocalized over
      two unit cells of the LiF crystal (approximately 8 A). This structure changes
      only modestly during the course of its life, which establishes it unambiguously
      as a Frenkel exciton and thus amenable to a simplified theoretical description.
      Our results resolve an old controversy about excitons in the alkali halides and
      demonstrate the utility of IXS for imaging attosecond electron dynamics in
      condensed matter.

PMID- 18711147
TI  - Plant foods and oestrogen receptor alpha- and beta-defined breast cancer:
      observations from the Malmo Diet and Cancer cohort.
AB  - The associations between plant foods and breast cancer incidence are
      inconsistent. The objective of this study was to examine prospectively the
      association between dietary fibre, plant foods and breast cancer, especially the
      association between plant food intake and oestrogen receptor (ER) alpha- and beta
      defined breast cancer. Among women without prevalent cancer from the population
      based prospective Malmo Diet and Cancer cohort (n = 15 773, 46-75 years at
      baseline), 544 women were diagnosed with incident invasive breast cancer during a
      mean follow-up of 10.3 years. Information on dietary habits was collected by a
      modified diet history method. ER status of the tumours was determined by
      immunohistochemistry using tissue microarray. Cox proportional hazards regression
      estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer
      associated with fibre and 11 plant food groups. High-fibre bread was
      significantly associated with a decreased breast cancer incidence (HR, 0.75; 95%
      CI, 0.57-0.98, for highest compared with lowest quintile). The other plant food
      groups were not significantly associated with breast cancer incidence. There was
      a tendency for a negative association for high-fibre bread among ERalpha (+)
      breast cancer (P for trend = 0.06) and ERbeta (+) breast cancer (P for trend =
      0.06). Fried potatoes were statistically significantly associated with increased
      risk of ERbeta (-) breast cancer (P = 0.01). This study suggests that different
      plant foods may be differently associated with breast cancer, with fibre-rich
      bread showing an inverse association. We did not observe strong evidence for
      differences in incidence according to the ERalpha and ERbeta status of breast
      cancer.

PMID- 18711148
TI  - A functional polymorphism in the miR-146a gene is associated with the risk for
      hepatocellular carcinoma.
AB  - A G > C polymorphism (rs2910164) is located in the stem region opposite to the
      mature miR-146a sequence, which results in a change from G:U pair to C:U mismatch
      in the stem structure of miR-146a precursor. Here, we elucidated the biological
      significance of this polymorphism, based on cancer association study and cell
      model system. The cancer association study included 479 hepatocellular carcinoma
      (HCC) and 504 control subjects. We found that the genotype distribution of this
      polymorphism in HCC cases was significantly different from that in control
      subjects (P = 0.026). The association between the genotype and the risk of HCC
      was further analyzed using multivariate unconditional logistic regression, with
      adjustment for sex, age and hepatitis B virus status. The results revealed that
      male individuals with GG genotype were 2-fold more susceptible to HCC (odds ratio
      = 2.016, 95% confidence interval = 1.056-3.848, P = 0.034) compared with those
      with CC genotype. We next examined the influence of this polymorphism on the
      production of mature miR-146a and found that G-allelic miR-146a precursor
      displayed increased production of mature miR-146a compared with C-allelic one.
      Further investigations disclosed that miR-146a could obviously promote cell
      proliferation and colony formation in NIH/3T3, an immortalized but non
      transformed cell line. These data suggest that the G > C polymorphism in miR-146a
      precursor may result in important phenotypic traits that have biomedical
      implications. Our findings warrant further investigations on the relation between
      microRNA polymorphism and human diseases.

PMID- 18711150
TI  - Do people with West Nile virus infection eventually return to normal health?

PMID- 18711149
TI  - Case-control analysis of nucleotide excision repair pathway and the risk of renal
      cell carcinoma.
AB  - In this population-based case-control study with 325 Caucasian renal cell
      carcinoma (RCC) patients and 335 controls matched to cases by age, gender and
      county of residence, we evaluated the associations between 13 potential
      functional polymorphisms in nine major nucleotide excision repair (NER) genes and
      RCC risk. In individual single nucleotide polymorphism analysis, after adjustment
      for multiple comparisons, a significantly decreased RCC risk was observed for the
      heterozygous genotype of XPD Asp312Asn [odds ratio (OR) = 0.62; 95% confidence
      interval (CI): 0.43-0.90] and for the heterozygous and homozygous variant
      genotypes combined in a dominant model (OR = 0.64; 95% CI: 0.46-0.89). The
      heterozygous AG genotype of XPA 5'untranslated region was at 1.78-fold increased
      risk (95% CI: 1.18-2.69) and the risk reached 2.43-fold (95% CI: 1.57-3.75) for
      the homozygous variant GG genotype; the risk was significant both in the dominant
      model and in the recessive model. In joint analysis, compared with individuals
      with fewer than five adverse alleles, individuals with five (OR = 1.17; 95% CI:
      0.71-1.93), six (OR = 1.66; 95% CI: 1.03-2.67), seven or more (OR = 1.85; 95% CI:
      1.16-2.95) exhibited a progressively increased risk of RCC (P for trend = 0.004).
      Further, there were significant interactions between NER pathway genes and sex,
      hypertension and obesity (all P for interaction <0.05). Our results strongly
      support that common sequence variants of the NER pathway genes predispose
      susceptible individuals to increased risk of RCC and that the association may be
      modified by gender, history of hypertension and obesity. These results need to be
      replicated in larger studies.

PMID- 18711151
TI  - Do low vitamin D levels increase risk for hip fracture?

PMID- 18711152
TI  - Appropriateness criteria for coronary angiography in angina: reliability and
      validity.
AB  - BACKGROUND: Evaluated criteria for tailoring the decision to perform coronary
      angiography in specific clinical scenarios are lacking. OBJECTIVE: To determine
      the reliability and prognostic validity of patient-specific appropriateness
      criteria for coronary angiography among patients with suspected angina pectoris.
      DESIGN: Prospective observational study. Two independent panels of clinicians
      scored 2400 patient-specific indications for coronary angiography as
      inappropriate, uncertain, or appropriate. Using a simple computer algorithm,
      patients were matched to 1 of these indications. SETTING: 6 urban ambulatory care
      clinics in the United Kingdom. PATIENTS: 9356 consecutive patients with recent
      onset chest pain in whom stable angina was suspected. MEASUREMENTS:
      Appropriateness ratings and clinical outcomes (coronary death and acute coronary
      syndrome events) over a median of 3 years of follow-up. RESULTS: 660 coronary
      deaths or acute coronary syndrome events occurred. Agreement between the 2 panels
      (reliability) on appropriateness category was moderate (weighted kappa = 0.58; P
      < 0.001). Use of subsequent angiography was strongly related to appropriateness
      category (P for linear trend <0.001) according to scores from either panel. Among
      patients judged as appropriate candidates for angiography, underuse was common
      (57% according to panel A and 71.3% according to panel B), and not undergoing
      coronary angiography was associated with higher coronary event rates than was
      undergoing the procedure. The hazard ratio after adjustment for age, sex,
      exercise electrocardiography result, and secondary prevention medication was
      similar according to panel A (2.78 [95% CI, 1.77 to 4.37]) and panel B (2.47 [CI,
      1.72 to 3.55]). LIMITATION: The study was too small to assess the relationship of
      angiography with coronary death and did not assess the reasons why patients did
      not receive angiography. CONCLUSION: Appropriateness scores offer prognostically
      valid criteria for judging which specific patients might benefit from coronary
      angiography. Patient-specific appropriateness scores help pinpoint areas where
      judgments diverge and are a promising tool for making guidelines more effective.

PMID- 18711153
TI  - Prognosis after West Nile virus infection.
AB  - BACKGROUND: The long-term prognosis of patients infected with West Nile virus is
      not well understood. OBJECTIVE: To describe the patterns of physical and mental
      function after infection with West Nile virus and to determine factors associated
      with recovery. DESIGN: Longitudinal cohort study. SETTING: Data were collected
      during home visits and from ambulatory clinics in 4 Canadian provinces.
      PARTICIPANTS: 156 persons with West Nile virus infection. MEASUREMENTS: Scores on
      the Physical Component Summary and Mental Component Summary of the Short Form-36,
      Depression Anxiety Stress Scale, and Fatigue Severity Scale. RESULTS: Physical
      and mental function, as well as mood and fatigue, seemed to return to normal
      within 1 year of symptom onset. Participants with neuroinvasive disease took
      slightly longer to recover. Maximum predicted recovery or rate of recovery in any
      domain did not differ between participants with meningoencephalitis and those
      with encephalitis. Lack of preexisting comorbid conditions was associated with
      faster recovery of physical function, whereas lack of comorbid conditions and
      male sex were associated with faster recovery of mental function. LIMITATIONS:
      The analysis excluded 7 patients who died shortly after diagnosis, so the study's
      estimates of prognosis may be overoptimistic. The authors did not formally assess
      neuropsychological difficulties. The estimates of recovery are relative to the
      U.S. population, not to participants' function levels before West Nile virus
      infection. CONCLUSION: Physical and mental outcome measures seem to normalize
      within approximately 1 year in patients with West Nile virus. The presence of
      preexisting comorbid conditions is associated with longer recovery.

PMID- 18711154
TI  - Serum 25-hydroxyvitamin D concentrations and risk for hip fractures.
AB  - BACKGROUND: The relationship between serum 25-hydroxyvitamin D [25(OH) vitamin D]
      concentration and hip fractures is unclear. OBJECTIVE: To see whether low serum
      25(OH) vitamin D concentrations are associated with hip fractures in community
      dwelling women. DESIGN: Nested case-control study. SETTING: 40 clinical centers
      in the United States. PARTICIPANTS: 400 case-patients with incident hip fracture
      and 400 control participants matched on the basis of age, race or ethnicity, and
      date of blood draw. Both groups were selected from 39 795 postmenopausal women
      who were not using estrogens or other bone-active therapies and who had not had a
      previous hip fracture. MEASUREMENTS: Serum 25(OH) vitamin D was measured and
      patients were followed for a median of 7.1 years (range, 0.7 to 9.3 years) to
      assess fractures. RESULTS: Mean serum 25(OH) vitamin D concentrations were lower
      in case-patients than in control participants (55.95 nmol/L [SD, 20.28] vs. 59.60
      nmol/L [SD, 18.05]; P = 0.007), and lower serum 25(OH) vitamin D concentrations
      increased hip fracture risk (adjusted odds ratio for each 25-nmol/L decrease,
      1.33 [95% CI, 1.06 to 1.68]). Women with the lowest 25(OH) vitamin D
      concentrations (< or =47.5 nmol/L) had a higher fracture risk than did those with
      the highest concentrations (> or =70.7 nmol/L) (adjusted odds ratio, 1.71 [CI,
      1.05 to 2.79]), and the risk increased statistically significantly across
      quartiles of serum 25(OH) vitamin D concentration (P for trend = 0.016). This
      association was independent of number of falls, physical function, frailty, renal
      function, and sex-steroid hormone levels and seemed to be partially mediated by
      bone resorption. LIMITATIONS: Few case-patients were nonwhite women. Bone mineral
      density and parathyroid hormone levels were not accounted for in the analysis.
      CONCLUSION: Low serum 25(OH) vitamin D concentrations are associated with a
      higher risk for hip fracture.

PMID- 18711155
TI  - The ADVANTAGE seeding trial: a review of internal documents.
AB  - BACKGROUND: Seeding trials, clinical studies conducted by pharmaceutical
      companies that are designed to seem as if they answer a scientific question but
      primarily fulfill marketing objectives, have not been described in detail.
      PURPOSE: To describe a known seeding trial, ADVANTAGE (Assessment of Differences
      between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and
      Effectiveness), through documents of the trial sponsor, Merck & Co. (Whitehouse
      Station, New Jersey). DATA SOURCES: Merck internal and external correspondence,
      reports, and presentations elicited to inform legal proceedings of Cona v Merck
      and Co., Inc., and McDarby v Merck and Co., Inc. The documents were created
      between 1998 and 2006. DATA EXTRACTION: An iterative case-study process of
      review, discussion, and re-review of documents to identify themes relevant to the
      design and conduct of ADVANTAGE. To supplement the case-study review, the authors
      did a systematic review of the literature to identify published manuscripts
      focused on seeding trials and their conduct. DATA SYNTHESIS: Review of the
      documents revealed 3 key themes: The trial was designed by Merck's marketing
      division to fulfill a marketing objective; Merck's marketing division handled
      both the scientific and the marketing data, including collection, analysis, and
      dissemination; and Merck hid the marketing nature of the trial from participants,
      physician investigators, and institutional review board members. Although the
      systematic review of the literature identified 6 articles that focused on the
      practice of seeding trials, none provided documentary evidence of their existence
      or conduct. LIMITATIONS: The legal documents in these cases provide useful, but
      limited, information about the practices of the pharmaceutical industry. This
      description of 1 company's actions is incomplete and may have limited
      generalizability. CONCLUSION: Documentary evidence shows that ADVANTAGE is an
      example of marketing framed as science. The documents indicate that ADVANTAGE was
      a seeding trial developed by Merck's marketing division to promote prescription
      of Vioxx (rofecoxib) when it became available on the market in 1999.

PMID- 18711156
TI  - Narrative review: furosemide for hypercalcemia: an unproven yet common practice.
AB  - Although primary hyperparathyroidism is the most common cause of hypercalcemia,
      cancer is the most common cause requiring inpatient intervention. An estimated
      10% to 20% of all patients with cancer have hypercalcemia at some point in their
      disease trajectory, particularly in advanced disease. Aggressive saline hydration
      and varying doses of furosemide continue to be the standard of care for emergency
      management. However, a review of the evidence for the use of furosemide in the
      medical management of hypercalcemia yields only case reports published before the
      introduction of bisphosphonates, in contrast to multiple randomized, controlled
      trials supporting the use of bisphosphonates. The use of furosemide in the
      management of hypercalcemia should no longer be recommended.

PMID- 18711157
TI  - Navigating language barriers under difficult circumstances.
AB  - The proportion of the U.S. population with limited English proficiency is
      growing. Physicians often find themselves caring for patients with limited
      English proficiency in settings with limited language services. There has been
      little exploration of the decisions physicians face when providing care across
      language barriers. The authors offer a conceptual framework to aid physicians in
      thinking through difficult choices about language services and provide responses
      to common questions encountered in the care of patients with limited English
      proficiency. Specifically, they describe 4 factors that should inform the
      decision to call an interpreter (the clinical situation, degree of language gap,
      available resources, and patient preference), discuss who may be an appropriate
      interpreter, and offer strategies for when a professional interpreter is not
      available. The authors use a hypothetical case to illustrate how decisions about
      language services may evolve over the course of an interaction. This conceptual
      and practical approach can help clinicians to improve the quality of care
      provided to patients with limited English proficiency.

PMID- 18711158
TI  - Hereditary hemochromatosis: time for targeted screening.
AB  - The discovery of the HFE gene in 1996 heralded a decade of major advances in the
      understanding of the mechanisms that control iron absorption and body iron
      stores. A genetic definition of the common form of hereditary hemochromatosis
      became possible, and testing for the common causative HFE mutations is now widely
      available in clinical laboratories. Several population screening studies have
      confirmed that disease penetrance in HFE-related hereditary hemochromatosis is
      lower than previously believed, making universal population-based screening for
      this disorder unattractive. However, hereditary hemochromatosis may still cause
      morbidity and mortality because of iron overload. Early detection and use of
      appropriate therapy can prevent these manifestations and can only be achieved by
      targeted case finding. In this article, the authors draw attention again to
      hereditary hemochromatosis as a cause of preventable organ dysfunction and
      propose targeted case finding for Caucasian men of Northern European ancestry.

PMID- 18711159
TI  - The nomogram epidemic: resurgence of a medical relic.
AB  - The obsolete calculators known as nomograms have become epidemic in recent
      medical literature. The frequency of articles in PubMed retrieved with this
      search term nearly doubled between 1990 to 1999 and 2000 to 2007. Popular in
      medicine from about 1925 to 1975, a nomogram is a crude graphical means for
      solving an equation by placing a straightedge across several scales. Today, most
      reported nomograms are inconsistent with both established definitions and half a
      century of clinical use. The need for nomograms disappeared with the advent of
      personal computing. Instead of constructing nomograms, authors should develop
      software, such as prediction models, that can either be downloaded to personal
      digital assistants or be used on the Internet. Modern computing features both
      accuracy and speed; nomograms offer only the latter.

PMID- 18711160
TI  - Assessing appropriateness of coronary angiography: another step in improving
      quality.

PMID- 18711161
TI  - Seeding trials: just say "no".

PMID- 18711162
TI  - The death of a clinician-educator.

PMID- 18711164
TI  - The prevalence of high-risk human papillomavirus in women with different types of
      cervical cancer.

PMID- 18711165
TI  - Resistant Behcet disease responsive to anakinra.

PMID- 18711167
TI  - Why choose serum cystatin C levels over serum creatinine levels as a serologic
      marker of kidney function?

PMID- 18711168
TI  - The effect of green tea on simvastatin tolerability.

PMID- 18711169
TI  - Multicenter study using paraffin-embedded tumor tissue testing PITX2 DNA
      methylation as a marker for outcome prediction in tamoxifen-treated, node
      negative breast cancer patients.
AB  - PURPOSE: We recently reported DNA methylation of the paired-like homeodomain
      transcription factor 2 (PITX2) gene to be strongly correlated with increased risk
      of recurrence in node-negative, hormone receptor-positive, tamoxifen-treated
      breast cancer patients using fresh frozen specimens. Aims of the present study
      were to establish determination of PITX2 methylation for routine analysis in
      formalin-fixed paraffin-embedded (FFPE) breast cancer tissue and to test PITX2
      DNA methylation as a biomarker for outcome prediction in an independent patient
      cohort. PATIENTS AND METHODS: Real-time polymerase chain reaction (PCR)
      technology was validated for FFPE tissue by comparing methylation measurements in
      FFPE specimens with those in fresh frozen specimens from the same tumor. The
      impact of PITX2 methylation on time to distant metastasis was then evaluated in
      FFPE specimens from hormone receptor-positive, node-negative breast cancer
      patients (n = 399, adjuvant tamoxifen monotherapy). RESULTS: Reproducibility of
      the PCR assay in replicate measurements (r(s) > or = 0.95; n = 150) and
      concordant measurements between fresh frozen and FFPE tissues (r(s) = 0.81; n =
      89) were demonstrated. In a multivariate model, PITX2 methylation added
      significant information (hazard ratio = 2.35; 95% CI, 1.20 to 4.60) to
      established prognostic factors (tumor size, grade, and age). CONCLUSION: PITX2
      methylation can be reliably assessed by real-time PCR technology in FFPE tissue.
      Together with our earlier studies, we have accumulated substantial evidence that
      PITX2 methylation analysis holds promise as a practical assay for routine
      clinical use to predict outcome in node-negative, tamoxifen-treated breast
      cancer, which might allow, based on future validation studies, the identification
      of low-risk patients who may be treated by tamoxifen alone.

PMID- 18711170
TI  - Urgent need for a new staging system in advanced colorectal cancer.
AB  - Despite recent advances in the medical treatment of metastatic colorectal cancer
      (mCRC), which include irinotecan- and oxaliplatin-based first-line regimens, the
      concept of planned sequential therapy involving three active agents during the
      course of a patient's treatment and the increasing use of targeted monoclonal
      antibodies, 5-year survival rates for patients with advanced CRC remain
      unacceptably low. For patients with CRC liver metastases, liver resection remains
      the only chance of cure, with 5-year survival rates ranging from 25% to 40%.
      However, 80% to 85% of patients with stage IV CRC have liver disease which is
      considered unresectable at presentation. The rapid expansion in the use of
      improved combination chemotherapy regimens plus or minus biologics, to render
      initially unresectable metastases resectable has increased the percentage of
      patients eligible for potentially curative surgery. However, the current staging
      criteria for CRC patients with metastatic disease do not reflect these recent
      changes or the fact that there is also a large variation in the survival of
      patients with stage IV CRC. For example the survival for a patient with a
      solitary, resectable liver metastasis is better than that for a patient with
      stage III disease. A new staging system is therefore needed that acknowledges
      both the improvements that have been made in surgical techniques for resectable
      metastases and the impact of modern chemotherapy on rendering initially
      unresectable CRC liver metastases resectable, while at the same time
      distinguishing between patients with a chance of cure at presentation and those
      for whom only palliative treatment is possible.

PMID- 18711171
TI  - Internal mammary nodes in breast cancer: diagnosis and implications for patient
      management -- a systematic review.
AB  - The management of internal mammary nodes (IMNs) in breast cancer is
      controversial. Surgical series from the 1950s showed that one third of breast
      cancer patients had IMN involvement, with a higher risk in patients with medial
      tumors and/or positive axillary nodes. IMN metastasis has similar prognostic
      importance as axillary nodal involvement. However, after three randomized trials
      showed no survival benefit from extended mastectomy compared with radical or
      modified radical mastectomy, IMN dissection was largely abandoned. Recently,
      lymphoscintigraphy studies have renewed interest in IMN evaluation. Approximately
      one fifth of internal mammary sentinel nodes are pathologic, although most
      centers do not perform IMN biopsies because of concerns about morbidity and lack
      of established survival benefit. In addition, results from randomized trials
      testing the value of postmastectomy irradiation and a meta-analysis of 78
      randomized trials have provided high levels of evidence that local-regional tumor
      control is associated with long-term survival improvements. This benefit was
      limited to trials that used systemic therapy, which was not routinely
      administered in the earlier surgical studies, although the contribution from IMN
      treatment is unclear. IMN irradiation has also been shown to cause increased
      cardiac morbidity. Before mature results from current randomized trials assessing
      the benefit of IMN irradiation become available, lymphoscintigraphy may be used
      to help guide decisions regarding systemic and local-regional treatment. However,
      even in patients with visualized primary IMN drainage, the potential benefit of
      treatment should be balanced against the risk of added morbidity.

PMID- 18711172
TI  - Zoledronic acid prevents bone loss in premenopausal women undergoing adjuvant
      chemotherapy for early-stage breast cancer.
AB  - PURPOSE: Adjuvant chemotherapy for breast cancer (BC) may be associated with
      increased rates of bone loss and decreased bone mineral density (BMD) and may
      lead to premature osteoporosis and increased fracture risk. We examined whether
      zoledronic acid (ZA) prevents bone loss in premenopausal women receiving
      chemotherapy for early-stage BC. PATIENTS AND METHODS: This study is a
      randomized, double-blind, multicenter, phase III trial comparing ZA (4 mg
      intravenously every 3 months) versus placebo for 1 year. Premenopausal women
      underwent serial BMD measurements before initiating chemotherapy and at 6 and 12
      months. The primary outcome was percent change in lumbar spine (LS) BMD at 6
      months. Secondary outcomes were percent change at any BMD site and markers of
      bone turnover at 12 months. Linear mixed model analysis for repeated measures was
      performed. RESULTS: Of 101 women who were randomly assigned and completed
      baseline evaluation, 96 completed the 6-month evaluation, and 85 completed the 12
      month evaluation. Baseline characteristics were comparable between the groups.
      Mean age was 42 years. Placebo was associated with significant decline in LS BMD
      at both 6 (2.4%) and 12 (4.1%) months. Similarly, total hip BMD declined by 0.8%
      at 6 months and 2.6% at 12 months. In contrast, BMD remained stable in ZA
      patients (P < .0001 compared with placebo). CONCLUSION: Premenopausal women
      receiving chemotherapy for BC sustained significant bone loss at the LS and hip,
      whereas BMD remained stable in women who received ZA. Administration of ZA during
      the first year of chemotherapy is an effective and well-tolerated strategy for
      preventing bone loss.

PMID- 18711173
TI  - Allogeneic hematopoietic stem-cell transplantation for chronic lymphocytic
      leukemia with 17p deletion: a retrospective European Group for Blood and Marrow
      Transplantation analysis.
AB  - PURPOSE: Patients with chronic lymphocytic leukemia (CLL) and 17p deletion (17p-)
      have a poor prognosis. Although allogeneic hematopoietic stem-cell
      transplantation (HCT) has the potential to cure patients with advanced CLL, it is
      not known whether this holds true for patients with 17p-CLL. PATIENTS AND
      METHODS: Baseline data from patients, for whom information on the presence of 17p
      CLL was available, were downloaded from the European Group for Blood and Marrow
      Transplantation database. Additional information on the course of CLL and follow
      up was collected with a questionnaire. RESULTS: A total of 44 patients with 17p
      CLL received allogeneic HCT between March 1995 and July 2006 from a matched
      sibling (n = 24) or an alternative donor (n = 20). 17p-CLL had been diagnosed by
      fluorescent in situ hybridization in 82% of patients and by conventional banding
      in 18% of patients. The median age was 54 years. Before HCT, a median of three
      lines of chemotherapy had been administered. At HCT, 53% of patients were in
      remission. Reduced-intensity conditioning was applied in 89% of patients. Acute,
      grade 2 to 4 graft-versus-host disease (GVHD) occurred in 43% of patients, and
      extensive chronic GVHD occurred in 53% of patients. At last follow-up, 19
      patients were alive, with a median observation time of 39 months (range, 18 to
      101 months). Three-year overall survival and progression-free survival rates were
      44% and 37%, respectively. The cumulative incidence of progressive disease at 4
      years was 34%. No late relapse occurred in nine patients with a follow-up longer
      than 4 years. CONCLUSION: Allogeneic HCT has the potential to induce long-term
      disease-free survival in patients with 17p-CLL.

PMID- 18711174
TI  - Neoadjuvant treatment of rectal carcinoma: assessment of health care services by
      physicians and lay persons.

PMID- 18711175
TI  - Analysis of herpes zoster events among bortezomib-treated patients in the phase
      III APEX study.
AB  - PURPOSE: The aim of this subset analysis was to determine if bortezomib treatment
      is associated with increased incidence of varicella-zoster virus (VZV)
      reactivation in patients with relapsed multiple myeloma (MM). PATIENTS AND
      METHODS: Incidence of herpes zoster was evaluated in 663 patients with relapsed
      MM from the phase III APEX trial comparing single-agent bortezomib with high-dose
      dexamethasone. RESULTS: Bortezomib was associated with a significantly higher
      incidence of herpes zoster compared with dexamethasone treatment (13%, 42 of 331
      v 5%, 15 of 332; P = .0002). Most herpes zoster infections were grade 1/2;
      incidences of grade 3/4 events (1.8% v 1.5%) and infections considered serious
      adverse events (1.5% v 0.9%) were similar between treatment arms, and no herpes
      zoster-related deaths occurred. Neither the time to onset of the herpes event nor
      the patients' absolute lymphocyte counts at baseline differed significantly
      between arms. VZV reactivation was the only herpes viral event noted to be
      significantly elevated in the bortezomib treatment group compared with the
      dexamethasone treatment group (P = .0002). The incidence of non-VZV-related
      herpes viral infections was comparable between arms. No additional risk factors
      for herpes zoster reactivation were identified. CONCLUSION: Further studies are
      needed to explain these observations and their implications; however, for
      patients treated with bortezomib or bortezomib-containing regimens, the risk of
      VZV reactivation should be monitored and routine use of antiviral prophylaxis
      considered.

PMID- 18711176
TI  - Analysis of survival by tumor response and other comparisons of time-to-event by
      outcome variables.

PMID- 18711177
TI  - Systems pathology and predicting outcome after radical prostatectomy.

PMID- 18711178
TI  - A lesser evil: prophylactic mastectomy for women at high risk for breast cancer.

PMID- 18711179
TI  - Just enough palliation: radiation dose and outcome in patients with non-small
      cell lung cancer.

PMID- 18711180
TI  - Systems pathology approach for the prediction of prostate cancer progression
      after radical prostatectomy.
AB  - PURPOSE: For patients with prostate cancer treated by radical prostatectomy, no
      current personalized tools predict clinical failure (CF; metastasis and/or
      androgen-independent disease). We developed such a tool through integration of
      clinicopathologic data with image analysis and quantitative immunofluorescence of
      prostate cancer tissue. PATIENTS AND METHODS: A prospectively designed algorithm
      was applied retrospectively to a cohort of 758 patients with clinically localized
      or locally advanced prostate cancer. A model predicting distant metastasis and/or
      androgen-independent recurrence was derived from features selected through
      supervised multivariate learning. Performance of the model was estimated using
      the concordance index (CI). RESULTS: We developed a predictive model using a
      training set of 373 patients with 33 CF events. The model includes androgen
      receptor (AR) levels, dominant prostatectomy Gleason grade, lymph node
      involvement, and three quantitative characteristics from hematoxylin and eosin
      staining of prostate tissue. The model had a CI of 0.92, sensitivity of 90%, and
      specificity of 91% for predicting CF within 5 years after prostatectomy. Model
      validation on an independent cohort of 385 patients with 29 CF events yielded a
      CI of 0.84, sensitivity of 84%, and specificity of 85%. High levels of AR
      predicted shorter time to castrate prostate-specific antigen increase after
      androgen deprivation therapy (ADT). CONCLUSION: The integration of
      clinicopathologic variables with imaging and biomarker data (systems pathology)
      resulted in a highly accurate tool for predicting CF within 5 years after
      prostatectomy. The data support a role for AR signaling in clinical progression
      and duration of response to ADT.

PMID- 18711181
TI  - Gene panel model predictive of outcome in men at high-risk of systemic
      progression and death from prostate cancer after radical retropubic
      prostatectomy.
AB  - PURPOSE: In men who are at high-risk of prostate cancer, progression and death
      from cancer after radical retropubic prostatectomy (RRP), limited prognostic
      information is provided by established prognostic features. The objective of this
      study was to develop a model predictive of outcome in this group of patients.
      METHODS: Candidate genes were identified from microarray expression data from 102
      laser capture microdissected prostate tissue samples. Candidates were
      overexpressed in tumor compared with normal prostate and more frequently in
      Gleason patterns 4 and 5 than in 3. A case control study of 157 high-risk
      patients, matched on Gleason score and stage with systemic progression or death
      of prostate cancer as the end point, was used to evaluate the expression of
      candidate genes and build a multivariate model. Tumor was collected from the
      highest Gleason score in paraffin-embedded blocks and the gene expression was
      quantified by real-time reverse transcription polymerase chain reaction.
      Validation of the final model was performed on a separate case-control study of
      57 high-risk patients who underwent RRP. RESULTS: A model incorporating gene
      expression of topoisomerase-2a, cadherin-10, the fusion status based on ERG,
      ETV1, and ETV4 expression, and the aneuploidy status resulted in a 0.81 area
      under the curve (AUC) in receiver operating characteristic statistical analysis
      for the identification of men with systemic progression and death from high grade
      prostate cancer. The AUC was 0.79 in the independent validation study.
      CONCLUSION: The model can identify men with high-risk prostate cancer who may
      benefit from more intensive postoperative follow-up and adjuvant therapies.

PMID- 18711182
TI  - Influence of year of diagnosis, patient age, and sociodemographic status on
      recommending adjuvant radiation treatment for stage I testicular seminoma.
AB  - PURPOSE: Adjuvant radiation therapy (ART) for stage I seminoma can cause adverse
      late effects and alternative postorchiectomy management strategies have been
      developed. This study evaluated ART trends in the United States and the impact of
      clinical and sociodemographic factors on ART recommendations. METHODS: Of men
      diagnosed with stage I seminoma from 1990 through 2004, 3,125 were identified
      using the Surveillance, Epidemiology, and End Results cancer registry. A
      multivariable logistic regression analysis was performed to assess whether there
      was a significant association between diagnosis year, diagnosis age, race, county
      education level, region, tumor size, tumor category, and the recommendation for
      ART. RESULTS: There was a significant association (P < .001) between later year
      of diagnosis and a decrease in ART recommendation. Compared with men diagnosed in
      1990 to 1994, men diagnosed in 1995 to 1999, and 2000 to 2004 were less likely to
      have ART (adjusted odds ratio [OR], 0.63; 95% CI, 0.48 to 0.84; and OR, 0.49; 95%
      CI, 0.37 to 0.63, respectively). There also was a significant association (P <
      .001) between county education level and ART recommendation. Men residing in
      counties with the highest education level were more likely to receive ART than
      men residing in counties with the lowest education level (OR, 2.12; 95% CI, 1.59
      to 2.82). Also, men older than 30 years were more likely to receive ART than men
      age 30 or younger (OR, 1.26; 95% CI, 1.03 to 1.55). CONCLUSION: ART
      recommendations for stage I seminoma are declining. Men in less educated regions
      and the youngest men were less likely to receive a recommendation for ART.

PMID- 18711183
TI  - Psychological reactions, quality of life, and body image after bilateral
      prophylactic mastectomy in women at high risk for breast cancer: a prospective 1
      year follow-up study.
AB  - PURPOSE: To prospectively evaluate body image, sexuality, emotional reactions
      (anxiety, depression), and quality of life in a sample of women having increased
      risk for breast cancer before and 6 months and 1 year after bilateral
      prophylactic mastectomy (BPM), and to compare preoperative expectations of the
      operation with postoperative reactions concerning the impact on six areas of the
      women's lives. PATIENTS AND METHODS: A total of 90 of 98 consecutive women who
      underwent BPM during October 1997 to December 2005 were included. Data were
      collected by self-administered questionnaires (eg, Hospital Anxiety and
      Depression scale, Swedish Short Term-36 Health Survey, Body Image Scale, Sexual
      Activity Questionnaire) before the operation (n = 81), and 6 (n = 71) and 12
      months (n = 65) after BPM. RESULTS: Anxiety decreased over time (P = .0004). No
      corresponding difference was found for depression. No differences in health
      related quality of life over time were found, with one exception. A substantial
      proportion of the women reported problems with body image 1 year after BPM (eg,
      self consciousness, 48%; feeling less sexually attractive, 48%; and
      dissatisfaction with the scars, 44%). Sexual pleasure was rated lower 1-year post
      BPM as compared with before operation (P = .005), but no differences over time in
      habit, discomfort, or activity were found. CONCLUSION: No negative effects on
      anxiety, depression, and quality of life were found. Anxiety and social
      activities improved. Negative impact on sexuality and body image was reported.

PMID- 18711184
TI  - Gemcitabine plus Paclitaxel versus Paclitaxel monotherapy in patients with
      metastatic breast cancer and prior anthracycline treatment.
AB  - PURPOSE: The objective of this phase III global study was to compare the efficacy
      of gemcitabine plus paclitaxel (GT) versus paclitaxel in patients with advanced
      breast cancer. It was designed as a pivotal study for the approval of G for a
      breast cancer treatment indication. PATIENTS AND METHODS: Patients who relapsed
      after adjuvant anthracyclines were randomly assigned to gemcitabine,1,250 mg/m(2)
      days 1 and 8 plus paclitaxel, 175 mg/m(2) on day 1; or, to paclitaxel at same
      dose on day 1 (both arms administered every 21 days, unblinded). The primary end
      point was overall survival (OS) and secondary end points were time to progression
      (TTP), response rate (RR), progression-free survival, response duration, and
      toxicity. This final OS analysis was planned at 380 deaths. RESULTS: A total of
      266 patients were randomly assigned to GT and 263 to paclitaxel. Median survival
      on GT was 18.6 months versus 15.8 months on paclitaxel (log-rank P = . 0489),
      with an adjusted Cox hazard ratio of 0.78 (95% CI, 0.64 to 0.96; P = .0187). The
      TTP was longer (6.14 v 3.98 months; log-rank P = .0002) and the RR was better
      (41.4% v 26.2%; P = .0002) on GT. There was more grade 3 to 4 neutropenia on GT
      and grade 2 to 4 fatigue and neuropathy were slightly more prevalent on GT.
      CONCLUSION: This phase III study documents a role for gemcitabine in advanced
      breast cancer after anthracycline-based adjuvant therapy. The results establish
      GT as a reasonable choice for women who require cytoreduction with manageable
      toxicities and validate ongoing testing of GT in the adjuvant setting.

PMID- 18711185
TI  - Influence of pre- and postdiagnosis physical activity on mortality in breast
      cancer survivors: the health, eating, activity, and lifestyle study.
AB  - PURPOSE: To investigate the association between pre- and postdiagnosis physical
      activity (as well as change in prediagnosis to postdiagnosis physical activity)
      and mortality among women with breast cancer. PATIENTS AND METHODS: This was a
      prospective observational study of 933 women enrolled onto the Health, Eating,
      Activity, and Lifestyle Study who were diagnosed with local or regional breast
      cancer between 1995 and 1998 and observed until death or September 2004,
      whichever came first. The primary outcomes measured were total deaths and breast
      cancer deaths. The primary exposures were physical activity in the year before
      and 2 years after diagnosis and the pre- to postdiagnosis change in physical
      activity. RESULTS: Compared with inactive women, the multivariable hazard ratios
      (HRs) for total deaths for women expending at least 9 metabolic equivalent hours
      per week (approximately 2 to 3 h/wk of brisk walking) were 0.69 (95% CI, 0.45 to
      1.06; P = .045) for those active in the year before diagnosis and 0.33 (95% CI,
      0.15 to 0.73; P = .046) for those active 2 years after diagnosis. Compared with
      women who were inactive both before and after diagnosis, women who increased
      physical activity after diagnosis had a 45% lower risk of death (HR = 0.55; 95%
      CI, 0.22 to 1.38), and women who decreased physical activity after diagnosis had
      a four-fold greater risk of death (HR = 3.95; 95% CI, 1.45 to 10.50). CONCLUSION:
      Moderate-intensity physical activity after a diagnosis of breast cancer may
      improve prognosis.

PMID- 18711186
TI  - Predicting change in academic abilities after conformal radiation therapy for
      localized ependymoma.
AB  - PURPOSE: Conformal radiation therapy (CRT) aims to limit the highest radiation
      dose to the tissue volume at risk while sparing surrounding normal tissues. This
      study investigated whether treatment of childhood ependymoma with CRT would
      preserve cognitive function. Academic competence was chosen as the primary
      outcome measure given it is a measure of applied cognitive abilities in a child's
      natural setting. PATIENTS AND METHODS: Eighty-seven pediatric patients diagnosed
      with ependymoma received CRT in which doses ranging from 54.0 to 59.4 Gy were
      prescribed to the postoperative tumor bed with a 10-mm clinical target volume
      margin. Cognitive testing was conducted at the start of CRT, 6 months, and
      annually after the start of CRT. The median length of follow-up was 59.6 months.
      Academic testing included subtests from the Wechsler Individual Achievement Test
      (WIAT) and the Achenbach Child Behavior Checklist. RESULTS: Linear mixed models
      with random coefficients revealed a modest but significant decline in reading
      scores during follow-up (WIAT slope estimate -0.064 +/- 0.028 points/month; P =
      .026). Math and spelling performance remained stable. Supratentorial tumor
      location and multiple surgeries were predictive of worse reading performance at
      CRT baseline. Male sex, longer symptomatic interval, pre-CRT chemotherapy, pre
      existing endocrine deficiencies, hydrocephalus, and younger age at CRT (< 5
      years) were predictive of a significant decline in reading scores over time.
      CONCLUSION: CRT may result in better long-term cognitive outcomes when compared
      to conventional radiation therapy approaches. Reading appears more vulnerable
      than other academic skills and may decline over time despite stable intellectual
      functioning.

PMID- 18711187
TI  - Reinduction platform for children with first marrow relapse of acute
      lymphoblastic Leukemia: A Children's Oncology Group Study[corrected].
AB  - PURPOSE: Treatment of childhood relapsed acute lymphoblastic leukemia (ALL)
      remains a significant challenge. The goal of the Children's Oncology Group (COG)
      AALL01P2 study was to develop a safe and active chemotherapy reinduction
      platform, which could be used to evaluate novel agents in future trials. PATIENTS
      AND METHODS: One hundred twenty-four patients with ALL and first marrow relapse
      received three, 35-day blocks of reinduction chemotherapy: 69 with early relapse
      (ER; < 36 months from initial diagnosis) and 55 with late relapse (LR). Minimal
      residual disease (MRD) was measured by flow cytometry after each treatment block.
      RESULTS: Second complete remission (CR2) rates at the end of block 1 in 117
      assessable patients were 68% +/- 6% for ER (n = 63) and 96% +/- 3% for LR (n =
      54; P < .0001). Five of seven patients with T-cell ALL (T-ALL) failed to achieve
      CR2. Among patients in CR2, MRD greater than 0.01% was detected at the end of
      block 1 in 75% +/- 7% of ER (n = 36) versus 51% +/- 8% of LR (n = 43; P = .0375)
      and 12-month event-free survival was 80% +/- 7% versus 58% +/- 7% in MRD-negative
      versus positive patients (P < .0005). Blocks 2 and 3 of therapy resulted in
      reduction of MRD burden in 40 of 56 patients who were MRD positive after block 1.
      Toxicity was acceptable during all three blocks with five deaths (4%) from
      infections. CONCLUSION: The AALL01P2 regimen is a tolerable and active
      reinduction platform, suitable for testing in combination with novel agents in B
      precursor ALL. Alternative strategies are needed for T-ALL. Serial MRD
      measurements were feasible and prognostic of outcome.

PMID- 18711188
TI  - Randomized phase II trial of a toll-like receptor 9 agonist oligodeoxynucleotide,
      PF-3512676, in combination with first-line taxane plus platinum chemotherapy for
      advanced-stage non-small-cell lung cancer.
AB  - PURPOSE: This study assessed the efficacy of the combination of standard taxane
      plus platinum chemotherapy with the synthetic Toll-like receptor 9-activating
      oligodeoxynucleotide PF-3512676 in patients with non-small-cell lung cancer
      (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB to IV
      NSCLC were randomly assigned (one to two ratio) to receive four to six cycles of
      taxane/platinum chemotherapy alone or with 0.2 mg/kg of subcutaneous PF-3512676
      on days 8 and 15 of each 3-week cycle. The primary end point was objective
      response rate (ORR). RESULTS: Baseline demographics were similar between
      treatment arms, although significantly more patients in the PF-3512676 arm had
      stage IV disease (85% compared with 62% in the chemotherapy-alone arm). The
      modified intent-to-treat analysis (n = 111) demonstrated a 38% ORR (confirmed and
      unconfirmed) in the PF-3512676 arm (n = 74) and 19% in the chemotherapy-alone arm
      (n = 37) by investigator evaluation. Blinded, independent radiologic review for
      90 patients showed a similar trend in confirmed response rate (19% and 11%,
      respectively). Median survival was 12.3 months in the PF-3512676 arm and 6.8
      months in the chemotherapy-alone arm, and 1-year survival was 50% and 33%,
      respectively. Mild to moderate local injection site reactions and flu-like
      symptoms were the most common PF-3512676-related adverse events, but grade 3/4
      neutropenia, thrombocytopenia, and anemia were all reported more commonly for
      patients in the PF-3512676 arm. CONCLUSION: The addition of PF-3512676 to taxane
      plus platinum chemotherapy for first-line treatment of NSCLC improves objective
      response and may improve survival. Confirmatory phase III trials are ongoing.

PMID- 18711189
TI  - Performing nondiagnostic research biopsies in irradiated tissue: a review of
      scientific, clinical, and ethical considerations.
AB  - PURPOSE: Recent development of drugs that target specific pathways in tumors has
      increased scientific interest in studying drug effects on tumor tissue. As a
      result, biopsies have become an important part of many early-phase clinical
      trials. Performing nondiagnostic tumor biopsies raises technical and ethical
      concerns mostly related to the use of a potentially harmful procedure with no
      potential benefit to the patient. This issue is complicated by uncertainty about
      whether performing biopsies in irradiated fields adds significant risk. This
      article reviews the clinical, scientific, and ethical considerations involved in
      performing nondiagnostic tumor biopsies in competent adults for research
      purposes, with a focus on biopsies performed in the setting of therapeutic
      irradiation. METHODS: Clinical trials that performed biopsies during or within 4
      months of the completion of radiotherapy were identified with a literature
      review. RESULTS: Twenty-nine studies with 2,160 patients were identified. Sixteen
      of 29 studies reported adverse events (AEs) but did not report active evaluation
      for biopsy complications. Ten studies did not mention AEs within the study
      report. At least three studies actively evaluated patients for biopsy
      complications. Taking this into consideration, 17 (>1%) of 2,160 patients were
      reported to have biopsy complications, although reporting of AEs was suboptimal
      in most studies. CONCLUSION: Limited data suggest that biopsies can be performed
      in irradiated tissues without clinically significant excess risk. Ongoing and
      future trials including nondiagnostic research biopsies should record and report
      AEs related to this procedure to provide additional data on safety and toxicity.

PMID- 18711190
TI  - Economic evaluation of sunitinib malate for the first-line treatment of
      metastatic renal cell carcinoma.
AB  - PURPOSE: To assess the cost effectiveness and cost utility of sunitinib malate as
      a first-line treatment in metastatic renal cell carcinoma (mRCC) compared with
      interferon-alfa (IFN-alpha) and interleukin-2 (IL-2) from a US societal
      perspective. METHODS: A Markov model was developed to simulate disease
      progression and to determine progression-free survival, total life-years (LYs),
      and quality-adjusted life-years (QALYs) gained. Model parameters were derived
      from the pivotal trial of sunitinib, published literature, government sources,
      and clinical experts' opinions. The model included trial-based adverse events
      (AEs). Costs of drug treatment, routine follow-up, AEs, disease progression, and
      best supportive care (BSC) of terminally ill patients were included. Results were
      tested using probabilistic and deterministic sensitivity analyses. RESULTS:
      Treatment with sunitinib is associated with a gain in progression-free years of
      0.41 and 0.35 over IFN-alpha and IL-2. The estimated gains over IFN-alpha were
      0.11 LYs and 0.14 QALYs, and over IL-2 were 0.24 LYs and 0.20 QALYs. Both IFN
      alpha and sunitinib treatments dominate IL-2 treatment; the incremental cost
      effectiveness ratio of sunitinib versus IFN-alpha was $18,611 per progression
      free year gained and $67,215 per LY gained, and the cost-utility ratio is $52,593
      per QALY gained (at a 5% discount rate). Sensitivity analyses found the results
      to be most sensitive to utility values during treatment, the cost of sunitinib,
      and the cost of BSC. Model results were robust to changes in other model
      variables. CONCLUSION: These results suggest that sunitinib is a cost-effective
      alternative to IFN-alpha as a first-line treatment for mRCC.

PMID- 18711191
TI  - Palliative thoracic radiotherapy for lung cancer: a systematic review.
AB  - PURPOSE: The optimal dose of radiotherapy (RT) to palliate symptomatic advanced
      lung cancer is unclear. We systematically reviewed randomized controlled trials
      (RCTs) of palliative thoracic RT. METHODS: RCTs comparing two or more dose
      fractionation schedules were reviewed using the random-effects model of a freely
      available information management system. The relative risk and 95% CI for each
      outcome were presented in Forrest plots. Exploratory analysis comparing dose
      schedules after conversion to the time-adjusted biologically equivalent dose
      (BED) was performed to investigate for a dose-response relationship. RESULTS: A
      total of 13 RCTs involving 3,473 randomly assigned patients were identified.
      Outcomes included symptom palliation, overall survival, toxicity, and
      reirradiation rate. For symptom control in assessable patients, lower-dose (LD)
      RT was comparable with higher-dose (HD), except for the total symptom score
      (TSS): 65.4% of LD and 77.1% of HD patients had improved TSS (P = .003). Greater
      likelihood of symptom improvement was seen with schedules of 35 Gy(10) versus
      lower BED. At 1 year after HD and LD RT, 26.5% versus 21.7% of patients were
      alive, respectively (P = .002). Sensitivity analysis suggests this survival
      improvement was seen with 35 Gy(10) BED schedules compared with LDs. Physician
      assessed dysphagia was significantly greater in the HD arm (20.5% v 14.9%; P =
      .01), and the likelihood of reirradiation was 1.2-fold higher after LD RT.
      CONCLUSION: No significant differences were observed for specific symptom-control
      end points, although improvement in survival favored HD RT. Consideration of
      palliative thoracic RT of at least 35 Gy(10) BED may therefore be warranted, but
      must be weighed against increased toxicity and greater time investment.

PMID- 18711193
TI  - American Society of Clinical Oncology clinical practice guidelines: opportunities
      and challenges.
AB  - The American Society of Clinical Oncology (ASCO) published its first clinical
      practice guideline, which focused on the use of hematopoietic colony-stimulating
      factors, in 1994. Since then, ASCO has published 24 additional guidelines or
      technology assessments on a range of topics and is developing 11 additional
      guidelines. Guidelines are among ASCO's most valued products, according to
      membership surveys and data from the JCO.org Web site. However, the same data
      from ASCO members have highlighted a number of limitations to the guideline
      program. These relate to the timelines of guideline updates, difficulties
      locating guidelines and related products, and challenges to implementing ASCO
      guidelines in everyday clinical practice. This article outlines the concrete
      steps that the ASCO Health Services Committee (HSC) is taking to address these
      limitations, including the institution of a more aggressive guideline updating
      schedule, a transition from narrative to systematic literature reviews to support
      the practice recommendations, a new Board of Directors-approved policy to permit
      endorsement of other groups' guidelines, and a robust Clinical Tools and
      Resources program that offers a range of guideline dissemination and
      implementation aids. Additional work is underway to establish stronger and deeper
      collaborations with practicing oncologists to expand their role in the review,
      field testing, and implementation of guideline clinical tools and resources.
      Finally, the HSC is discussing evaluation of the guidelines program to maximize
      the impact of ASCO clinical practice guidelines on clinical decision making and,
      ultimately, the quality of cancer care.

PMID- 18711192
TI  - New technologies for human cancer imaging.
AB  - Despite technical advances in many areas of diagnostic radiology, the detection
      and imaging of human cancer remains poor. A meaningful impact on cancer
      screening, staging, and treatment is unlikely to occur until the tumor-to
      background ratio improves by three to four orders of magnitude (ie, 10(3)- to
      10(4)-fold), which in turn will require proportional improvements in sensitivity
      and contrast agent targeting. This review analyzes the physics and chemistry of
      cancer imaging and highlights the fundamental principles underlying the detection
      of malignant cells within a background of normal cells. The use of various
      contrast agents and radiotracers for cancer imaging is reviewed, as are the
      current limitations of ultrasound, x-ray imaging, magnetic resonance imaging
      (MRI), single-photon emission computed tomography, positron emission tomography
      (PET), and optical imaging. Innovative technologies are emerging that hold great
      promise for patients, such as positron emission mammography of the breast and
      spectroscopy-enhanced colonoscopy for cancer screening, hyperpolarization MRI and
      time-of-flight PET for staging, and ion beam-induced PET scanning and near
      infrared fluorescence-guided surgery for cancer treatment. This review explores
      these emerging technologies and considers their potential impact on clinical
      care. Finally, those cancers that are currently difficult to image and quantify,
      such as ovarian cancer and acute leukemia, are discussed.

PMID- 18711194
TI  - Choice and interpretation of statistical tests used when competing risks are
      present.
AB  - In clinical cancer research, competing risks are frequently encountered. For
      example, individuals undergoing treatment for surgically resectable disease may
      experience recurrence near the removed tumor, metastatic recurrence at other
      sites, occurrence of second primary cancer, or death resulting from noncancer
      causes before any of these events. Two quantities, the cause-specific hazard
      function and the cumulative incidence function, are commonly used to summarize
      outcomes by event type. Tests for event-specific differences between treatment
      groups may thus be based on comparison of (a) cause-specific hazards via a log
      rank or related test, or (b) the cumulative incidence functions via one of
      several available tests. Inferential results for tests based on these different
      metrics can differ considerably for the same cause-specific end point. Depending
      on the questions of principal interest, one or both metrics may be appropriate to
      consider. We present simulation study results and discuss examples from cancer
      clinical trials to illustrate these points and provide guidance for analysis when
      competing risks are present.

PMID- 18711195
TI  - The difficult patient.

PMID- 18711196
TI  - Osteonecrosis of the jaw related to bevacizumab.

PMID- 18711197
TI  - Metastatic parathyroid carcinoma to the liver treated with radiofrequency
      ablation and transcatheter arterial embolization.

PMID- 18711198
TI  - Extramedullary myeloid sarcoma of the breast.

PMID- 18711199
TI  - Risk of ipsilateral lung cancer after postmastectomy radiotherapy and smoking:
      does the possible triumph over the actual?

PMID- 18711200
TI  - Superiority of reduced-intensity conditioning for Hodgkin's lymphoma.

PMID- 18711201
TI  - Secondary erythrocytosis produced by the tyrosine kinase inhibitors sunitinib and
      sorafenib.

PMID- 18711202
TI  - Perspective on "Chemotherapy for advanced prostate cancer: 25 years later": is it
      a mirage or an oasis?

PMID- 18711203
TI  - Clinical impact of discordance in serum albumin measurements on myeloma
      international staging system.

PMID- 18711204
TI  - Development and implementation of an integrated, multi-modality, user-centered
      interactive dietary change program.
AB  - Computer-tailored behavior change programs offer the potential for reaching large
      populations at a much lower cost than individual or group-based programs.
      However, few of these programs to date appear to integrate behavioral theory with
      user choice, or combine different electronic modalities. We describe the
      development of an integrated CD-ROM and interactive voice response dietary change
      intervention that combines behavioral problem-solving theory with a high degree
      of user choice. The program, WISE CHOICES, is being evaluated as part of an
      ongoing trial. This paper describes the program development, emphasizing how user
      preferences are accommodated, and presents implementation and user satisfaction
      data. The program was successfully implemented; the linkages among the central
      database, the CD-ROM and the automated telephone components were robust, and
      participants liked the program almost as well as a counselor-delivered dietary
      change condition. Multi-modality programs that emphasize the strengths of each
      approach appear to be feasible. Future research is needed to determine the
      program impact and cost-effectiveness compared with counselor-delivered
      intervention.

PMID- 18711205
TI  - Gender factors associated with sexual abstinent behaviour of rural South African
      high school going youth in KwaZulu-Natal, South Africa.
AB  - The cross-sectional study investigated South African rural high school learners'
      choice of sexual abstinence in order to be able to develop tailored health
      education messages. All Grade 9 learners from one class at each of 10 randomly
      selected rural high schools participated. The Integrated Model for Motivational
      and Behavioural Change was used to elicit attitudes, social influences, self
      efficacy and intentions towards sexual abstinence. Chi-square and t-tests were
      used for bivariate analysis. In total, 454 learners, mean age 16.7 years
      (standard deviation 1.41) range 14-20 years, participated, of whom 246 (54.2%)
      were female. When comparing learners reporting abstinence (n=252) with those not
      abstinent (n=202), abstinent learners were significantly more often females
      (P<0.005), younger (16.5 years versus 17.1 years, P<0.005) and drank less alcohol
      (P<0.005). Abstaining girls believed that their friends and parents think that
      they should abstain from sex, that their friends abstained from sex and that
      abstinence helped them to mature emotionally. Abstinent boys expressed intentions
      to abstain from sex until marriage. Targeted intervention research is required to
      encourage South African rural high school learners to delay their sexual
      initiation to reduce their risk of human immunodeficiency virus infection.
      Different abstinent messages are needed for boys and girls to address the
      different patterns of behaviour observed.

PMID- 18711206
TI  - Social and emotional training in Swedish schools for the promotion of mental
      health: an effectiveness study of 5 years of intervention.
AB  - The school is an obvious arena for interventions designed to promote mental
      health among children. A set of educational techniques named social and emotional
      learning, which focuses on students' self-control, social competence, empathy,
      motivation and self-awareness, has shown promising results in the United States.
      This is a study of the application of a similar method in Sweden (referred to as
      social and emotional training) for school years 2000/2001 through to 2004/2005.
      It is an effectiveness rather than an efficacy study, largely administered by
      school personnel, which relates duration of the training (1-5 years) to a set of
      outcomes previously found to be associated with mental health. Positive and
      significant effects were found on five of seven variables: internalizing
      problems, externalizing problems, mastery (reflecting self-efficacy or
      hopelessness), self-image and self-esteem and contentment in school. Effect sizes
      were medium. Somewhat surprisingly, no relationship was found between the
      intervention and the promotion of social skills. Nor was there any detectable
      long-term impact on bullying. Controlling for student gender did not moderate any
      of the effects.

PMID- 18711207
TI  - Structural and dynamic interfacial properties of the lipoprotein initiating
      domain of apolipoprotein B.
AB  - To better understand the earliest steps in the assembly of triglyceride (TG)-rich
      lipoproteins, we compared the biophysical and interfacial properties of two
      closely related apolipoprotein B (apoB) truncation mutants, one of which contains
      the complete lipoprotein initiating domain (apoB20.1; residues 1-912), and one of
      which, by virtue of a 50 amino acid C-terminal truncation, is incapable of
      forming nascent lipoproteins (apoB19; residues 1-862). Spectroscopic studies
      detected no major differences in secondary structure, and only minor differences
      in conformation and thermodynamic stability, between the two truncation mutants.
      Monolayer studies revealed that both apoB19 and apoB20.1 bound to and penetrated
      egg phosphatidylcholine (EPC) monolayers; however, the interfacial exclusion
      pressure of apoB20.1 was higher than apoB19 (25.1 mN/m vs. 22.8 mN/m). Oil drop
      tensiometry revealed that both proteins bound rapidly to the hydrophobic
      triolein/water interface, reducing interfacial tension by approximately 20 mN/m.
      However, when triolein drops were first coated with phospholipids (PL), apoB20.1
      bound with faster kinetics than apoB19 and also displayed greater interfacial
      elasticity (26.9 +/- 0.8 mN/m vs. 22.9 +/- 0.8 mN/m). These data establish that
      the transition of apoB to assembly competence is accompanied by increases in
      surface activity and elasticity, but not by significant changes in global
      structure.

PMID- 18711209
TI  - The selective COX-2 inhibitor celecoxib modulates sphingolipid synthesis.
AB  - Sphingolipids such as ceramides (Cers) play important roles in cell
      proliferation, apoptosis, and cell cycle regulation. An increased Cer level is
      linked to the cytotoxic effects of several chemotherapeutics. Various selective
      cyclooxygenase-2 (COX-2) inhibitors induce anti-proliferative effects in tumor
      cells. We addressed the possible interaction of the selective COX-2 inhibitors,
      coxibs, with the sphingolipid pathway as an explanation of their anti
      proliferative effects. Sphingolipids were measured using liquid chromatography
      tandem mass spectrometry. Treatment of various cancer cell lines with celecoxib
      significantly increased sphinganine, C(16:0)-, C(24:0)-, C(24:1)-dihydroceramide
      (dhCer) and led to a depletion of C(24:0)-, C(24:1)-Cer in a time- and
      concentration-dependent manner, whereas other coxibs had no effect. Using
      (13)C,(15)N-labeled l-serine, we demonstrated that the augmented dhCers after
      celecoxib treatment originate from de novo synthesis. Celecoxib inhibited the
      dihydroceramide desaturase (DEGS) in vivo with an IC(50) of 78.9 +/- 1.5 muM and
      increased total Cer level about 2-fold, indicating an activation of sphingolipid
      biosynthesis. Interestingly, inhibition of the sphingolipid biosynthesis by
      specific inhibitors of l-serine palmitoyltransferase diminished the anti
      proliferative potency of celecoxib. In conclusion, induction of de novo synthesis
      of sphingolipids and inhibition of DEGS contribute to the anti-proliferative
      effects of celecoxib.

PMID- 18711208
TI  - Origins of intestinal ABCA1-mediated HDL-cholesterol.
AB  - The origins of cholesterol utilized by intestinal ABCA1 were investigated in the
      human intestinal cell line Caco-2. Influx of apical membrane cholesterol
      increases ABCA1 mRNA and mass, resulting in enhanced efflux of HDL-cholesterol.
      Luminal (micellar) cholesterol and newly synthesized cholesterol are not
      transported directly to ABCA1 but reach the ABCA1 pool after incorporation into
      the apical membrane. Depleting the apical or the basolateral membrane of
      cholesterol by cyclodextrin attenuates the amount of cholesterol transported by
      ABCA1 without altering ABCA1 expression. Filipin added to the apical side but not
      the basal side attenuates ABCA1-mediated cholesterol efflux, suggesting that
      apical membrane "microdomains," or rafts, supply cholesterol for HDL. Preventing
      cholesterol esterification increases the amount of cholesterol available for HDL.
      Ezetimibe, a Niemann-Pick C1-like 1 protein inhibitor, does not alter ABCA1
      mediated cholesterol efflux. U18666A and imipramine, agents that mimic
      cholesterol trafficking defects of Neimann-Pick type C disease, attenuate
      cholesterol efflux without altering ABCA1 expression; thus, intestinal NPC1 may
      facilitate cholesterol movement to ABCA1. ABCA1-mediated cholesterol efflux is
      independent of cholesterol synthesis. The results suggest that following
      incorporation into plasma membrane and rafts of the apical membrane,
      dietary/biliary and newly synthesized cholesterol contribute to the ABCA1 pool
      and HDL-cholesterol. NPC1 may have a role in this process.

PMID- 18711210
TI  - Plasma phospholipid transfer activity is essential for increased atherogenesis in
      PLTP transgenic mice: a mutation-inactivation study.
AB  - Plasma phospholipid transfer protein (PLTP) interacts with HDL particles and
      facilitates the transfer of phospholipids from triglyceride (TG)-rich
      lipoproteins to HDL. Overexpressing human PLTP in mice increases the
      susceptibility to atherosclerosis. In human plasma, high-active and low-active
      forms of PLTP exist. To elucidate the contribution of phospholipid transfer
      activity to changes in lipoprotein metabolism and atherogenesis, we developed
      mice expressing mutant PLTP, still able to associate with HDL but lacking
      phospholipid transfer activity. In mice heterozygous for the LDL receptor,
      effects of the mutant and normal human PLTP transgene (mutPLTP tg and PLTP tg,
      respectively) were compared. In PLTP tg mice, plasma PLTP activity was increased
      2.9-fold, resulting in markedly reduced HDL lipid levels. In contrast, in mutPLTP
      tg mice, lipid levels were not different from controls. Furthermore, hepatic VLDL
      TG secretion was stimulated in PLTP tg mice, but not in mutPLTP tg mice. When
      mice were fed a cholesterol-enriched diet, atherosclerotic lesion size in PLTP tg
      mice was increased more than 2-fold compared with control mice, whereas in
      mutPLTP tg mice, there was no change. Our findings demonstrate that PLTP transfer
      activity is essential for the development of atherosclerosis in PLTP transgenic
      mice, identifying PLTP activity as a possible target to prevent atherogenesis,
      independent of plasma PLTP concentration.

PMID- 18711211
TI  - Factors in tissue handling and processing that impact RNA obtained from formalin
      fixed, paraffin-embedded tissue.
AB  - Formalin-fixed, paraffin-embedded (FFPE) tissue is the most common specimen
      available for molecular assays on tissue after diagnostic histopathological
      examination. RNA from FFPE tissue suffers from strand breakage and cross-linking.
      Despite excellent extraction methods, RNA quality from FFPE material remains
      variable. To address the RNA quality factors within FFPE tissues, we studied RNA
      quality, isolating individual elements of the tissue fixation and processing
      including length of fixation in formalin and the type of buffer incorporated in
      the fixative. We examined the impact of the length of the tissue processing cycle
      as well. The optimal fixation period of 12-24 hr in phosphate-buffered formalin
      resulted in better-quality RNA. Longer tissue processing times were associated
      with higher quality RNA. We determined that the middle region of gene suffers
      less damage by these processes as shown by real-time quantitative RT-PCR. These
      data provide key information for the development of methods of analysis of gene
      expression in archival FFPE tissues and contribute to the establishment of
      objective standards for the processing and handling of tissue in surgical
      pathology. This manuscript contains online supplemental material at
      http://www.jhc.org. Please visit this article online to view these materials.

PMID- 18711213
TI  - The emerging role of faith community nurses in prevention and management of
      chronic disease.
AB  - Faith community nursing, formerly known as parish nursing, is one model of care
      that relies heavily on older registered nurses (RNs) to provide population-based
      and other nonclinical services in community settings. Faith community nursing
      provides services not commonly available in the traditional health care system
      (e.g., community case management, community advocacy, community health
      education). With appropriate support, this model of nursing could be expanded
      into other settings within the community and has the potential to draw on the
      skills of experienced RNs to provide communities with services that address unmet
      health care needs.

PMID- 18711212
TI  - Immunocytological and preliminary immunohistochemical studies of prothymosin
      alpha, a human cancer-associated polypeptide, with a well-characterized
      polyclonal antibody.
AB  - Prothymosin alpha (ProTalpha) is a nuclear polypeptide of great biological and,
      possibly clinical, importance, because its expression levels have been associated
      with early diagnosis/prognosis of human cancer. It is therefore interesting to
      raise easily available and cost-effective antibodies that would be applied to
      develop reliable ProTalpha immunodiagnostics. In this study, New Zealand white
      rabbits and laying hens were parallel immunized against intact ProTalpha or the
      synthetic fragments ProTalpha[1-28], ProTalpha[87-109], and ProTalpha[101-109],
      all conjugated to keyhole limpet hemocyanin (KLH). The corresponding antibodies G
      and Y were immunochemically evaluated in parallel with ELISA and Western blot
      systems and applied to fluorescence immunocytology experiments using various
      cancer cell lines and normal cells. The antibody G raised against ProTalpha[101
      109]/KLH had excellent functional characteristics in the Western blot and
      immunocytology experiments, where the fluorescent signal was almost exclusively
      shown in the cell nucleus independently of the cells assayed. The above antibody
      has been applied to preliminary IHC staining of human cancer prostate tissues,
      leading to a high percentage of clearly and intensively stained nuclei in the
      adenocarcinoma tissue; this antibody can be further used in cancer tissue
      immunostaining and in research concerning the role of ProTalpha in tumorigenesis.

PMID- 18711217
TI  - Just and unjust: E. E. Just (1883-1941).

PMID- 18711218
TI  - Tilting at quixotic trait loci (QTL): an evolutionary perspective on genetic
      causation.
AB  - Recent years have seen great advances in generating and analyzing data to
      identify the genetic architecture of biological traits. Human disease has
      understandably received intense research focus, and the genes responsible for
      most Mendelian diseases have successfully been identified. However, the same
      advances have shown a consistent if less satisfying pattern, in which complex
      traits are affected by variation in large numbers of genes, most of which have
      individually minor or statistically elusive effects, leaving the bulk of genetic
      etiology unaccounted for. This pattern applies to diverse and unrelated traits,
      not just disease, in basically all species, and is consistent with evolutionary
      expectations, raising challenging questions about the best way to approach and
      understand biological complexity.

PMID- 18711220
TI  - The qSD12 locus controls offspring tissue-imposed seed dormancy in rice.
AB  - Seed component structures were grouped into maternal and offspring (embryo and
      endosperm) tissues to characterize a dormancy quantitative trait locus (QTL) for
      tissue-specific function using a marker-assisted genetic approach. The approach
      was devised to test if genotypic/allelic frequencies of a marker tightly linked
      to the QTL deviate from Mendelian expectations in germinated and nongerminated
      subpopulations derived from a segregation population of partially after-ripened
      seeds and was applied to the dormancy QTL qSD12 and qSD7-1 in a nearly isogenic
      background of rice. Experimental results unambiguously demonstrated that qSD12
      functions in the offspring tissue(s) and suggested that qSD7-1 may control
      dormancy through the maternal tissues. These experiments also provide the first
      solid evidence that an offspring tissue-imposed dormancy gene contributes to the
      segregation distortion in a mapping population developed from partially after
      ripened seeds and, in part, to the germination heterogeneity of seeds from hybrid
      plants. Offspring and maternal tissue-imposed dormancy genes express in very
      early and late stages of the life cycle, respectively, and interact to provide
      the species with complementary adaptation strategies. The qSD12 locus was
      narrowed to the region of approximately 600 kbp on a high-resolution map to
      facilitate cloning and marker-assisted selection of the major dormancy gene.

PMID- 18711219
TI  - Mutagenic and recombinagenic responses to defective DNA polymerase delta are
      facilitated by the Rev1 protein in pol3-t mutants of Saccharomyces cerevisiae.
AB  - Defective DNA replication can result in substantial increases in the level of
      genome instability. In the yeast Saccharomyces cerevisiae, the pol3-t allele
      confers a defect in the catalytic subunit of replicative DNA polymerase delta
      that results in increased rates of mutagenesis, recombination, and chromosome
      loss, perhaps by increasing the rate of replicative polymerase failure. The
      translesion polymerases Pol eta, Pol zeta, and Rev1 are part of a suite of
      factors in yeast that can act at sites of replicative polymerase failure. While
      mutants defective in the translesion polymerases alone displayed few defects,
      loss of Rev1 was found to suppress the increased rates of spontaneous mutation,
      recombination, and chromosome loss observed in pol3-t mutants. These results
      suggest that Rev1 may be involved in facilitating mutagenic and recombinagenic
      responses to the failure of Pol delta. Genome stability, therefore, may reflect a
      dynamic relationship between primary and auxiliary DNA polymerases.

PMID- 18711221
TI  - How safe is hand-assisted laparoscopic donor nephrectomy?--results of 200 live
      donor nephrectomies by two different techniques.
AB  - BACKGROUND: Despite the rapid introduction of laparoscopic living donor
      nephrectomy, doubts exist about safety compared with open surgery. Early series
      have often reported on selective donor groups. We present a consecutive,
      prospective analysis of morbidity following hand-assisted laparoscopic donor
      nephrectomy (HALDN) compared with historical controls undergoing open donation
      (ODN) in a total of 200 living donors at a single UK centre. METHODS: The results
      of 144 consecutively performed HALDN donors were compared to 56 preceding ODN
      patients. Patients with multiple arteries, right-sided nephrectomies and obesity
      were included. Data on recovery and complications were collected prospectively
      and consecutively. RESULTS: There were two (1.4%) major complications in the
      HALDN group and one in the ODN group (1.8%, P = 0.629). Additionally, there were
      24 minor complications in 23 HADLN patients (16.7%), compared with 21 in 21 ODN
      patients (37.5%, P = 0.003). Time taken to return to normal activity and mean
      post-operative stay was significantly shorter for the HALDN group. There was no
      mortality in either group. CONCLUSIONS: Contrary to concerns, we report a safe
      experience with HALDN with a low rate of major complications. Furthermore, our
      patients spend less time in hospital with an earlier return to normal activity
      compared with open donation.

PMID- 18711222
TI  - Association of chronic kidney disease with outcomes in chronic heart failure: a
      propensity-matched study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with increased mortality
      in patients with heart failure (HF). However, its association with
      hospitalization in HF patients has not been well studied. METHODS: Of 7788
      patients in the Digitalis Investigation Group trial, 3527 had CKD, defined by an
      estimated glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) body surface area
      (BSA). Propensity scores for CKD were calculated using a multivariable logistic
      regression model and used to match 2399 pairs of patients with and without CKD.
      Matched Cox regression analyses were used to estimate association of CKD with
      outcomes. RESULTS: All-cause hospitalization occurred in 1636 (rate, 4233/10,000
      person-years) and 1587 (rate, 3733/10,000 person-years) patients respectively,
      with and without CKD (matched hazard ratio [HR] for CKD, 1.18, 95% confidence
      interval [CI], 1.08-1.29; P < 0.0001). Matched HR for cardiovascular and HF
      hospitalization were respectively 1.17 (95% CI, 1.06-1.28, P = 0.002) and 1.28
      (95% CI, 1.13-1.45, P < 0.0001). Compared to GFR >or=60 ml/min/1.73 m(2) BSA, HR
      for all-cause hospitalization for GFR 45-59 and <45 ml/min/1.73 m(2) BSA were
      respectively 1.04 (95% CI, 0.94-1.16; P = 0.422) and 1.58 (95% CI, 1.34-1.87; P <
      0.0001). Similarly, HR for all-cause death for GFR 45-59 and <45 ml/min/1.73 m(2)
      BSA were respectively 1.03 (95% CI, 0.90-1.18; P = 0.651) and 1.70 (95% CI, 1.40
      2.07; P < 0.0001). Matched HR for death due to cardiovascular causes and
      progressive HF were respectively 1.24 (95% CI, 1.09-1.40; P = 0.001) and 1.42
      (95% CI, 1.16-1.72; P = 0.001). CONCLUSION: CKD was associated with increased
      mortality and hospitalization in ambulatory patients with chronic HF, which
      increased progressively with worsening kidney function.

PMID- 18711223
TI  - Neuronal viability is controlled by a functional relation between synaptic and
      extrasynaptic NMDA receptors.
AB  - N-methyl-D-aspartate receptors (NMDARs) are critical for synaptic plasticity that
      underlies learning and memory. But, they have also been described as a common
      source of neuronal damage during stroke and neurodegenerative diseases. Several
      studies have suggested that cellular location of NMDARs (synaptic or
      extrasynaptic) is a key parameter controlling their effect on neuronal viability.
      The aim of the study was to understand the relation between these two pools of
      receptors and to determine their implication in both beneficial and/or
      deleterious events related to NMDAR activation. We demonstrated that selective
      extrasynaptic NMDAR activation, as well as NMDA bath application, does not
      activate extracellular signal-regulated kinase (ERK) pathways, but induces
      mitochondrial membrane potential breakdown and triggers cell body and dendrite
      damages, whereas synaptic NMDAR activation is innocuous and induces a sustained
      ERK activation. The functional dichotomy between these two NMDAR pools is tightly
      controlled by glutamate uptake systems. Finally, we demonstrated that the only
      clinically approved NMDAR antagonist, memantine, preferentially antagonizes
      extrasynaptic NMDARs. Together, these results suggest that extrasynaptic NMDAR
      activation contributes to excitotoxicity and that a selective targeting of the
      extrasynaptic NMDARs represents a promising therapeutic strategy for brain
      injuries.

PMID- 18711224
TI  - Comparing folic acid pharmacokinetics among women of childbearing age: single
      dose ingestion of 1.1 versus 5 MG folic acid.
AB  - BACKGROUND: A 2001 study suggested that supplementation with 5 mg folic acid,
      among women of childbearing age, is needed to render maximum protection against
      neural tube defects (NTD). No human study is presently available which examined
      the pharmacokinetics of 5 mg folic acid. OBJECTIVE: To compare the
      pharmacokinetics of ingesting a single dose of 5 mg versus 1.1 mg folic acid
      contained in 2 prenatal multivitamins (PregVit and PregVit-Folic 5), and to
      estimate its contribution to steady-state folate levels. METHOD: The
      pharmacokinetics of 1.1 mg folic acid was determined in a previously published
      study. The method was replicated among 6 healthy, non-pregnant women who were
      given 5 mg folic acid to ingest. Blood samples were drawn and serum folate
      concentrations were measured at various time points during 10 hours post
      ingestion. Standard pharmacokinetic parameters were determined and compared with
      Student's t-test, when appropriate. RESULTS: The mean area under the curve (AUC)
      of 1.1 mg and 5 mg folic acid were 147.6 +/- 52.8 (ng/mL) x hr and 997.5 +/-
      271.9 (ng/mL) x hr, respectively (p<0.0002). An approximate 5-fold difference was
      detected in the peak concentrations (Cmax) between the 2 groups (p<0.0005),
      alongside a slight difference in the times to peak (Tmax) (p=0.02). The estimated
      steady-state serum folate concentrations produced by 1.1 mg and 5 mg folic acid
      were 6.2 +/- 2.2 ng/mL and 41.6 +/- 11.3 ng/mL, respectively (p<0.0002), prior to
      its summation with initial (baseline) steady-state levels. CONCLUSION: Single
      dose administration between 1.1 mg and 5 mg folic acid demonstrated linear
      pharmacokinetics, with approximately a 5-fold difference between the 2 doses in
      serum folate contribution to steady-state levels, under ideal adherence.

PMID- 18711225
TI  - [Out of hopelessness--problem solving training in suicide prevention].
AB  - Psychological studies have great importance in suicide prevention since
      psychological factors belong to the modifiable risk factors in suicide. These are
      the negative cognitive triad and hopelessness which are related to vague, over
      generalized autobiographical memory and lead to poor problem solving abilities.
      In this paper we review the most relevant clinical psychology studies and models
      such as the cognitive model of suicide as well as the entrapment theory by
      Williams (2004). In the second part we describe the frequently used method of
      problem solving training/therapy which can be used in either individual or group
      format. We hope that the problem solving skill training will soon become a part
      of suicide prevention in Hungary also, since short,focused and evidence based
      interventions are much needed in psychiatric care.

PMID- 18711226
TI  - [Features of borderline suicidality. Review of the literature].
AB  - Based on literature data the author reviews the features of borderline
      suicidality. Completed suicide in the context of chronic self-injurious behavior
      together with repeated low-lethality suicide attempts, is a special feature of
      borderline suicidal behavior. Parasuicidal behavior is not motivated by a genuine
      intent to die, but it is rather an effort to regulate emotions and interpersonal
      relationships. Impulsivity and poor emotion regulation appear to be the
      underlying psychopathological dimension of chronic parasuicidality.
      Parasuicidality can not be treated by acute interventions. To achieve symptom
      reduction, treatment must focus on the development of skills which are deficient
      in the patient. If acute-on-chronic risk is present, the clinician should pursue
      active intervention in order to protect the patient.

PMID- 18711227
TI  - [Hopelessness in patients presenting to their family physician].
AB  - In order to reduce suicide rate in Hungary, it is essential to screen for and
      detect individuals with high suicide risk. For people with suicidal thoughts and
      intentions often visit their GP, our intention was to assess the potential
      suicide risk amongst patients going to the GP's. Based on a former study, we
      assumed the rate of depression to be about 30% amongst patients waiting at the
      GP's consulting room, and that there would be suicidal patients too. A randomised
      study of 158 patients together with 91 matched controls was conducted in GP's
      practices. Four different scales were applied: Beck Hopelessness Scale, Beck
      Depression Scale, Beck's Anxiety Scale and Paykel's Life Event Scale.
      Unfortunately, our results showed a more serious picture than expected: people
      visiting the GP were significantly more depressed, hopeless and anxious than
      controls, and one third of them proved to be at high suicide risk. CONCLUSION:
      GPs can play an important role in suicide prevention, and should do as well.
      Hopelessness Scale and Beck's Depression Scale are reliable test materials for
      local doctors.

PMID- 18711228
TI  - [Investigation of problem solving skills among psychiatric patients].
AB  - According to our present knowledge depression and hopelessness play an important
      role in attempted suicide and the development of hopelessness seems to be closely
      associated with poor problem solving skills. In the present study we have used
      the internationally well-known MEPS (Means-Ends Problem Solving Test; a measure
      of social problem solving ability) in Hungary for the first time and combined
      with other tests. We intended to explore the cognitive risk factors that
      potentially play a role in the suicidal behavior in clinical population. In our
      study we compared a group of individuals who had attempted suicide to a
      nonsuicidal psychiatric control group and a normal control group (61 subjects in
      each group). Our results confirm the findings of others that psychiatric patients
      have difficulties in social problem solving compared to normal controls.
      Moreover, they generate less and poorer solutions. According to our data problem
      solving skills of the two clinical groups were similar. A strong positive
      correlation was found between poor problem solving skills, depression and
      hopelessness which may suggest that the development of problem solving skills
      could help to reduce negative mood.

PMID- 18711229
TI  - [The analysis of negative life events, hopelessness and coping strategies among
      psychotic patients].
AB  - Some theories explaining the background of suicidal attempts emphasise the role
      of depression, while others emphasise the role of hopelessness in the case of
      different psychological states, like psychosis. According to researches negative
      emotions, namely hopelessness predicts suicidal intentions more precisely than
      depression itself. In our study we measured the suicidal risk of our psychotic
      patients with hopelessness, depression and life event scales. Our results have
      implied that suicidal psychotic patient groups showed significantly more serious
      level of depression and hopelessness and had more negative life events than the
      non-suicidal group. Indeed, a sub-group could also be distinguished among
      suicidal psychotic patients in which the level of hopelessness predicts suicidal
      risk and not depression.

PMID- 18711230
TI  - [Inguinal hernia repair: classification and the choice of adequate anaesthesia
      techniques].
AB  - In spite of the great achievements in herniology, the problem of inguinal hernia
      is not solved. The adequate classification is a step to its proper treaty. The
      classification of the disease is presented in the article. The study confirms the
      benefits of local anaesthetic-based techniques over both general and spinal
      anaesthesia for inguinal hernia repair and presents new methods of treatment. The
      direct and indirect costs of anaesthesia for inguinal hernia repair are lowest
      when using local anaesthesia with or without sedation. Local anaesthesia-based
      techniques with conscious sedation fulfil all the requirements for the ideal
      ambulatory anaesthetic.

PMID- 18711231
TI  - [Donor supply of scalp and specificities of hair transplantation in Asians].
AB  - In 2005--2007 in a hair transplantation clinic 'Talizi' the flow of international
      patients increased dramatically, including those from Central and Eastern Asia.
      During this period 211 ethnic Asian patients underwent operations, including 146
      patients from South Korea, 2--from China, 62-- from Kazakhstan and 1--from
      Philippines. Black and straight hair give impact of low density due to
      considerable contrast with characteristic for Asians light color scalp;
      therefore, from the very beginning we tried to transplant as many grafts
      (follicular units - FU) as possible. For the operation we chose strip version
      (FUSS) that enables to receive large number of grafts. The scale of
      transplantation varied in a range of 1200-3800 FU, on average--2500-3000 FU.
      Though, even from the very first cases we faced specificities of ethnic Asian
      scalp that significantly complicated our work: low density and low hair/graft
      ratio in donor zone in contrast to information from special literature, and low
      laxity (flexibility) of the scalp. We set an objective to specify indicators of
      donor density (number of FU on a sq.cm and hair/FU ratio), to study bio
      mechanical specificities of ethnic Asian scalp and develop optimal surgical
      tactics for these patients after the evaluation of transplantation results.
      Observation group was composed of 211 patients from abovementioned countries and
      a sub-group--50 Korean patients for medium-scale hair transplantation (2000-3000
      FU) by strip version. Study of donor characteristics of these patients revealed
      low density--74 FU/cm2; on 1 cm2 grow only 121 hairs, whereas hair/FU ration was
      1,63. Strength required to close would edges (scalp tension power) varied from
      1,4 kg-f to 2,6 kg-f depending on scalp flexibility and number of transplanted
      grafts (strip width), and amounted on average to 2,16 +/- 0,02 kg-f, p < 0,001%.
      This indicator is about 1,5 times exceeding the one of ethnic Caucasian patient
      group (1,47 +/- 0,02 kg-f, p < 0,001%). Low donor density of our Korean patients
      compelled us to increase width of the obtained skin strip (sometimes to 2,5 cm)
      in order to get required number of grafts (FU). In case of low flexibility of the
      scalps this resulted in high percentage (10-15%) of wide (4-10 mm) scar formation
      in donor area. In order to find the way out from this situation (restrict the
      width of the strip to 1,5 cm without affecting FU to be transplanted in one
      operation), we proposed the combination of the strip version (FUSS) with FU
      extraction (FUE). While this solution increased the duration and price of the
      operation, we believe that it is the most optimal version in case of large-scale
      hair transplantation for the ethnic Asian patients.

PMID- 18711232
TI  - [Osteoplastic materials in the treatment of parodontosis].
AB  - Efficiency of bioactive osteoplastic composition HA-phage at a surgical stage of
      combined treatment of chronic generalized periodontitis was examined. The results
      obtained in the control and experimental groups proved that HA-phage allows
      reducing the time of treatment and to achieve remission of the disease. Out of 92
      patients with chronic generalized periodontitis 52 undertook microplasmic scalpel
      irradiator in complex treatment. The treatment course comprises 3-5 procedures.
      The quantity of manipulations is determined by the pathological process. Before
      and after the treatment the radiographic investigations were carried out in
      persons of both groups. 18 months later after the operation a bone regeneration
      was shown in 87,8% cases in the investigated group and 60,1%--in the control
      group patients. The therapy has shown positive results. So, the new method of
      treatment of chronic generalized periodontitis may prove to be more practical in
      clinical dentistry. Currently, it is possible to isolate highly purified BMSSCs
      from bone marrow using STRO-1. The management of periodontal defects has been an
      ongoing challenge in clinical periodontics. This is mainly a result of the fact
      that the tissues which comprise the periodontium, the periodontal ligament, and
      the cementum and alveolar bone represent three unique tissues in their own right.
      Thus, reconstruction of the periodontium is not just a simple matter of
      regenerating one tissue but involves at least three quite diverse and unique
      tissues. Taking into account the results of recent studies we hypothesize that
      mesenchymal stem cells transplantation should be a perspective approach in the
      treatment of periodontal defects. For this purpose we plan to perform an
      experimental investigations which will include an induction of periodontitis,
      purification of the bone marrow stem cells and their transplantation.

PMID- 18711233
TI  - Evaluation of pilot methadone maintenance therapy in Georgia (Caucasus).
AB  - Since December 2005 Methadone Treatment has been introduced in Georgia. Currently
      three programs are operating in the country covering 210 patients. The aim of
      this study was to assess the acceptability and effectiveness of the pilot
      methadone program. Case histories, registrations books, questionnaires were
      studied. Standardized RAB questionnaire was adapted as well. 60 patients (1
      female) were surveyed. Methadone program was well accepted. 92% of participants
      were satisfied with treatment. Only one patient left the program due to move
      away. Mean age of participants is 40, mean history of drug use is 15.3 years,
      16.7% are infected with Hep B, 80%--infected with Hep C, 11.7%--infected with
      HIV. There was a significant reduction (68% never uses) of illicit opioid use;
      daily use of psychotropic drugs reduced from 66.7% to 1.7%. Injecting risk
      behaviour significantly reduced from 17.98% to 0.98%; no significant change in
      sexual risk behaviour was observed (14.40% vs. 12.25%). Study findings suggest
      that Methadone Maintenance Treatment in Georgia is well accepted and effective in
      reducing illegal opioid use, injecting risk behavior, and improving the health
      status of participants. There is a need for scaling up opiate agonist treatment
      and introducing additional services within the framework of these programs.
      Further qualified monitoring and assessment in dynamics is needed.

PMID- 18711234
TI  - [Role of immune inflammatory activity in chronic heart failure progress].
AB  - Significant role of immune inflammatory reactions along with activation of the
      RAAS (rennin-angiotensin-aldosterone system) and the sympatho-adrenal system in
      CHF (chronic heart failure) pathogenesis is considered in the present survey
      article. Together with haemodynamic disorders activation of inflammatory
      reactions, which involve anti-inflammatory cytokines, is shown to be one of the
      main factors affecting CHF course and prognosis. Alteration of cytokine level is
      associated with injury level, gravity of the disease course and its clinical
      outcome. Prognostic value of determination of inflammation mediators as
      predictors of cardiovascular diseases and clinical outcomes is evaluated. Urgency
      of search for new medication in addition to "traditional preparations" used for
      the treatment of CHF is shown.

PMID- 18711235
TI  - [Clinical-EMG characteristic of myasthenia gravis associated with thyroid
      pathology].
AB  - On the basis of clinical-EMG analyses, the researches have revealed the criteria
      characteristic of myasthenia associated with thyroid pathologies. The myasthenia
      process associated with thyroid pathology is mainly characterized as of
      generalized average intensity. Alongside with mup-s with reduced duration and
      amplitude characteristic of myasthenia, EMG exposes potentials with comparatively
      long duration and high amplitude (mainly when the process is associated with
      thyreotoxycosis). It should also be noted that spontaneous activity is
      intensively expressed. Considering all the above mentioned, we can conclude that
      these changes show disfunctioning of mup-s rather than the character of synapses
      caused by the process associated with the myasthenia. The results of the research
      will facilitate the timely revelation of the process associated with myasthenia
      and will lead to the unfailing adequate pathogenetic treatment.

PMID- 18711236
TI  - [Prevalence of congenital dislocation of hip diffusion among the population of
      Lenkoran and Massaly region in Azerbaijan].
AB  - The occurrence of congenital hip dislocation in Lenkoran and Massaly areas of
      Azerbaijan Republic was studied. The population-genetic assessment in Lenkoran
      and Massaly regions was conducted. The phenotypic frequency of hip congenital
      dislocation according to Medical- Labor Expert Commission data are 0,065% and
      0,035% respectively. According to present survey congenital hip dislocation data
      are: 0, 7% and 0, 4% respectively. The results of the study demonstrate strong
      demand of accurate data on the occurrence of congenital and genetic diseases in
      Azerbaijan Republic. The highest prevalence of multiple-factor type of heredity
      indicates the necessity to control teratogen factors of the environment.

PMID- 18711237
TI  - [Imidazoline receptors].
AB  - An increasing number of studies suggest that the pharmacology and therapeutic
      potential of a family of imidazoline receptors continues to generate substantial
      interest of investigators. This review analyzes the functional role of
      imidazoline receptors, their subpopulation, distribution in the central and
      peripheral nervous system and action of related ligands. Besides to their
      brainstem location where I1-receptor sites play a significant role to regulate
      and modulate blood pressure, they also are found in different parts of brain with
      the highest densities in the striatum, pallidum, hippocampus, amygdala,
      substantia nigra, while I3-receptor sites were revealed in pancreas which
      enhances insulin secretion, I2-receptors are widely distributed in
      interpeduncular nucleus, arcuate and pineal gland and take a part in monoamine
      turnover. It is conclusion that imidazoline receptor in near future can become a
      therapeutic target in the treatment of diabetes, stroke, mood disorders and
      hyperalgesic condition.

PMID- 18711238
TI  - Ubiquitin-26s proteasome system. New therapeutic implications (review).
AB  - The article reviews Ubiquitin-26S proteasome system (UPS), which is an ATP
      dependent protein degradation mechanism in eukaryotic cells. UPS effects many
      principal substrates and cellular processes, therefore, it is not surprising that
      aberrations in the system may be implicated in pathogenesis of many diseases.
      Alterations in the UPS are correlated with a variety of human pathologies, like
      cancer, immunological disorders, inflammation, neurodegenerative, liver diseases
      and etc. It is believed that ubiquitin cascade components E1, E2, E3, ubiquitin,
      proteasome, substrate protein, are useful in discover of new therapeutic
      possibilities. All kinds of aberrations have been found in ubiquitin-26S
      proteasome system, among them: truncated version of ubiquitin (Acute
      Lymphoblastic Leukaemia), elongated ubiquitin (Alcoholic Liver Disease),
      suppressed proteasome, accelerative degradation, decreased rates of degradation
      and etc. As irreversible course of cell cycle is very sensitive to protein
      degradation process, each of these derangements may cause proliferative disorders
      and hence development of heavy diseases. It is too difficult to identify a narrow
      window between benefits and toxicity of drugs used in treatment of different
      diseases. That is why is so important to discover inhibitors or activators of
      intracellular mechanisms for protein degradation due to development of targeted
      therapy.

PMID- 18711239
TI  - Influence of water deprivation on morphological peculiarities of the neuronal
      organization in hypothalamic supraoptic and paraventricular nuclei of the rats.
AB  - In the present study a histochemical investigation of the SO and PV nuclei of the
      hypothalamic-pituitary neurosecretory system are presented at different periods
      of the water deprivation. The experiments were carried out on laboratory rats (n
      = 50), weighing 200-250 grams. The experimental and control animals days was
      maintained at different feeding ration. The control rats (I) were given food and
      water, the experimental animals (II, III, IV, V) for five days were given the dry
      food only. Following the 5-day water deprivation, the animals of the Groups III,
      IV, and V, had given free access to water for 15, 30, and 45 days. In order to
      investigate histological properties, the animals were rapidly beheaded. In order
      to reveal a neurosecrete, the 5-10 mm thick slices of the hypothalamus and
      pituitary gland were stained with the Nissle method. Evaluation of the
      morphological-functional state of the HPNSS a working scheme of the
      neurosecretory cycle has been utilized. Analysis of the above data allows
      concluding that following prolonged water deprivation, recovery level of the
      structural-metabolic components in the hypothalamic SO and PV nuclei is not
      uniform. Deeper morphological changes occur in the large-granular region than in
      the small-granular one, where no significant changes are found; respectively,
      these cells recover much earlier. Capacity for restoration of the structural
      metabolic complex varies and depends on functional properties of the cellular
      content of these nuclei.

PMID- 18711240
TI  - [Practical nutrition of refugees population in Georgia].
AB  - The aim of the present study is to work out the strategy of nutrition which will
      smooth the negative impact of alimentary factors and imbalanced food intake of
      refugees. The special questionnaire was developed. The evaluation of nutrition of
      400 members of 50 refugee families from 19 to 57 years old was conducted in
      Georgia. A study of 400 refugee populations in 2008 showed a strong positive
      association between acute malnutrition prevalence and death rates. The
      investigation revealed two main problems in the nutrition of refugees, which
      reflects the health: the environment and imbalanced food intake.

PMID- 18711241
TI  - [The evidence of matrix metalloproteinases and its tissue inhibitors in
      children's affected gingiva].
AB  - Matrix metalloproteinases (MMP) and its tissue inhibitors (TIMP) were studied in
      14 affected and 11 "control" samples from children in cases of dental extraction.
      Cytokeratin 14 coexpression also was analyzed in this materials by
      immunohistochemical study. Total RNA was extracted and the transcript levels for
      MMP-19 and TIMP-4 were determined by semi-quantitative real-time reverse
      transcription-polymerase Chain reaction (RT-PCR). The results demonstrated direct
      correlation between increased MMP/TIMP ration and inflamed gingival tissue
      breakdown.

PMID- 18711242
TI  - Efficient use of continuous, real-time prostate localization.
AB  - Recent technological advances make it possible to monitor prostate movement
      during radiation delivery. Using previously published data from 35 patients who
      underwent continuous localization during prostate cancer treatment, we simulated
      various interventions to identify the radiation-gating and patient-repositioning
      strategies that least prolonged the time to complete the daily treatment.
      Acceptable response protocols were those that resulted in at least 95% of
      patients' prostates remaining within the planning margins at least 95% of the
      time. Gating and repositioning were not necessary for margins of 7 or 10 mm
      because of the rarity of excursions at these margins. However, intervention was
      routinely necessary for margins of 3 and 5 mm. In simulated interventions for
      which the therapist could reposition the treatment couch without entering the
      room, the most time-efficient response protocol was to reposition the couch
      immediately after the prostate position was outside the treatment margins. In
      simulations in which the therapist had to enter the room to reposition the couch,
      overall treatment time could be reduced and accuracy could be increased by
      manually gating treatment for 11 and 21 s for 3- and 5-mm margins, respectively,
      before interrupting treatment to reposition the treatment couch.

PMID- 18711243
TI  - A tandem calibration method for kerma-area product meters.
AB  - For measurements of the kerma-area product (KAP) in diagnostic x-ray imaging, a
      method for calibrating field KAP meters with a reference KAP meter is presented.
      In this tandem calibration method, the field KAP chamber is positioned similarly
      as in measurements with patients. The reference KAP chamber is placed at a
      specified distance and used in the x-ray beam simultaneously with the field KAP
      chamber. The tandem method provides a feasible and practical way for calibrating
      field KAP meters of any type in their clinical position. Accurate measurements of
      the irradiation geometry are not required, but comprehensive calibration for the
      reference KAP meter is needed.

PMID- 18711244
TI  - Thimble ionization chambers in medium-energy x-ray beams and the role of
      constructive details of the central electrode: Monte Carlo simulations and
      measurements.
AB  - This paper presents investigations of thimble ionization chamber response in
      medium-energy kilovoltage x-ray beams (70-280 kVp, 0.09-3.40 mm Cu HVL). Two
      thimble ionization chambers (PTW30015 and PTW30016) were investigated, regarding
      the influence of the central electrode dimensions made of aluminum. Measurements
      were carried out in photon fields of different beam quality. Corresponding Monte
      Carlo simulations employing the EGSnrc Monte Carlo code system were performed.
      The simulations included the modelling of the x-ray tube and measurement setup
      for generation of x-ray spectra. These spectra were subsequently used to
      calculate the absorbed energy in the air cavity of the two thimble ionization
      chamber models and the air kerma at the reference point of the chambers.
      Measurements and simulations revealed an optimal diameter of the central
      electrode, concerning an almost energy-independent response of the ionizaton
      chamber. The Monte Carlo simulations are in good agreement with the measured
      values, expressed in beam quality correction factors k(Q). The agreement was
      generally within 0.6% but could only be achieved with an accurate model of the
      central electrode including its exact shape. Otherwise, deviations up to 8.5%
      resulted, decreasing with higher photon energies, which can be addressed to the
      high yield of the photoelectric effect in the electrode material aluminum at low
      photon energies.

PMID- 18711245
TI  - Simulation of cardiac motion on non-Newtonian, pulsating flow development in the
      human left anterior descending coronary artery.
AB  - This study aimed at investigating the effect of myocardial motion on pulsating
      blood flow distribution of the left anterior descending coronary artery in the
      presence of atheromatous stenosis. The moving 3D arterial tree geometry has been
      obtained from conventional x-ray angiograms obtained during the heart cycle and
      includes a number of major branches. The geometry reconstruction model has been
      validated against projection data from a virtual phantom arterial tree as well as
      with CT-based reconstruction data for the same patient investigated.
      Reconstructions have been obtained for a number of temporal points while linear
      interpolation has been used for all intermediate instances. Blood has been
      considered as a non-Newtonian fluid. Results have been obtained using the same
      pulse for the inlet blood flow rate but with fixed arterial tree geometry as well
      as under steady-state conditions corresponding to the mean flow rate. Predictions
      indicate that myocardial motion has only a minor effect on flow distribution
      within the arterial tree relative to the effect of the blood pressure pulse.

PMID- 18711246
TI  - A technique for generating phase-space-based Monte Carlo beamlets in radiotherapy
      applications.
AB  - As radiotherapy treatment planning moves toward Monte Carlo (MC) based dose
      calculation methods, the MC beamlet is becoming an increasingly common
      optimization entity. At present, methods used to produce MC beamlets have
      utilized a particle source model (PSM) approach. In this work we outline the
      implementation of a phase-space-based approach to MC beamlet generation that is
      expected to provide greater accuracy in beamlet dose distributions. In this
      approach a standard BEAMnrc phase space is sorted and divided into beamlets with
      particles labeled using the inheritable particle history variable. This is
      achieved with the use of an efficient sorting algorithm, capable of sorting a
      phase space of any size into the required number of beamlets in only two passes.
      Sorting a phase space of five million particles can be achieved in less than 8 s
      on a single-core 2.2 GHz CPU. The beamlets can then be transported separately
      into a patient CT dataset, producing separate dose distributions (doselets).
      Methods for doselet normalization and conversion of dose to absolute units of Gy
      for use in intensity modulated radiation therapy (IMRT) plan optimization are
      also described.

PMID- 18711247
TI  - Contrasting properties of gold nanoparticles for optical coherence tomography:
      phantom, in vivo studies and Monte Carlo simulation.
AB  - The possibility of using silica-gold nanoshells with 150 nm silica core size and
      25 nm thick gold shell as contrasting agents for optical coherence tomography
      (OCT) is analyzed. Experiments on agar biotissue phantoms showed that the
      penetration of nanoshells into the phantoms increases the intensity of the
      optical coherence tomography (OCT) signal and the brightness of the corresponding
      areas of the OCT image. In vivo experiments on rabbit skin demonstrated that the
      application of nanoshells onto the skin provides significant contrasting of the
      borders between the areas containing nanoshells and those without. This effect of
      nanoshells on skin in vivo is manifested by the increase in intensity of the OCT
      signal in superficial parts of the skin, boundary contrast between superficial
      and deep dermis and contrast of hair follicles and glands. The presence of
      nanoshells in the skin was confirmed by electron microscopy. Monte Carlo
      simulations of OCT images confirmed the possibility of contrasting skin-layer
      borders and structures by the application of gold nanoshells. The Monte Carlo
      simulations were performed for two skin models and exhibit effects of
      nanoparticles similar to those obtained in the experimental part of the study,
      thus proving that the effects originate exactly from the presence of
      nanoparticles.

PMID- 18711248
TI  - On the role of modeling parameters in IMRT plan optimization.
AB  - The formulation of optimization problems in intensity-modulated radiotherapy
      (IMRT) planning comprises the choice of various values such as function-specific
      parameters or constraint bounds. In current inverse planning programs that yield
      a single treatment plan for each optimization, it is often unclear how strongly
      these modeling parameters affect the resulting plan. This work investigates the
      mathematical concepts of elasticity and sensitivity to deal with this problem. An
      artificial planning case with a horse-shoe formed target with different opening
      angles surrounding a circular risk structure is studied. As evaluation functions
      the generalized equivalent uniform dose (EUD) and the average underdosage below
      and average overdosage beyond certain dose thresholds are used. A single IMRT
      plan is calculated for an exemplary parameter configuration. The elasticity and
      sensitivity of each parameter are then calculated without re-optimization, and
      the results are numerically verified. The results show the following. (1)
      elasticity can quantify the influence of a modeling parameter on the optimization
      result in terms of how strongly the objective function value varies under
      modifications of the parameter value. It also can describe how strongly the
      geometry of the involved planning structures affects the optimization result. (2)
      Based on the current parameter settings and corresponding treatment plan,
      sensitivity analysis can predict the optimization result for modified parameter
      values without re-optimization, and it can estimate the value intervals in which
      such predictions are valid. In conclusion, elasticity and sensitivity can provide
      helpful tools in inverse IMRT planning to identify the most critical parameters
      of an individual planning problem and to modify their values in an appropriate
      way.

PMID- 18711249
TI  - An investigation of flat panel equipment variables on image quality with a
      dedicated cardiac phantom.
AB  - Image quality (IQ) evaluation plays a key role in the process of optimization of
      new x-ray systems. Ideally, this process should be supported by real clinical
      images, but ethical issues and differences in anatomy and pathology of patients
      make it impossible. Phantom studies might overcome these issues. This paper
      presents the IQ evaluation of 30 cineangiographic films acquired with a cardiac
      flat panel system. The phantom used simulates the anatomy of the heart and allows
      the circulation of contrast agent boluses through coronary arteries. Variables
      investigated with influence on IQ and radiation dose are: tube potential,
      detector dose, added Copper filters, dynamic density optimization (DDO) and
      viewing angle. The IQ evaluation consisted of scoring 4 simulated calcified
      lesions located on different coronary artery segments in terms of degree of
      visualization. Eight cardiologists rated the lesions using a five-point scale
      ((1) lesion not visible to (5) very good visibility). Radiation doses associated
      to the angiograms are expressed in terms of incident air kerma (IAK) and
      effective dose that has been calculated with PCXMX software (STUK, Finland) from
      the exposure settings assuming a standard sized patient of 70 Kg. Mean IQ scores
      ranged from 1.68 to 4.88. The highest IQ scores were obtained for the angiograms
      acquired with tube potential 80 kVp, no added Cu filters, DDO 60%, RAO and LAO
      views and the highest entrance detector dose that has been used in the present
      study, namely 0.17 microGy/im. Radiation doses (IAK approximately 40 mGy and
      effective dose of 1 mSv) were estimated for angiograms acquired at 15 frames s(
      1), detector field-of-view 20 cm, and a length of 5 s. The following parameters
      improved the IQ factor significantly: a change in tube potential from 96 to 80
      kVp, detector dose from 0.10 microGy/im to 0.17 microGy/im, the absence of Copper
      filtration. DDO variable which is a post-processing parameter should be carefully
      evaluated because it alters the quality of the images independently of radiation
      exposure settings. The SAM anthropomorphic phantom has the advantage of
      visualization of stenotic lesions during the injection of a contrast agent and
      using an anatomical background. In the future, this phantom could potentially
      bridge the gap between physics tests and the clinical reality in the
      catheterization laboratory.

PMID- 18711251
TI  - A reconstruction algorithm for thermoacoustic tomography with compensation for
      acoustic speed heterogeneity.
AB  - An inverse reconstruction algorithm for thermoacoustic tomography (TAT) is
      proposed with the compensation for the acoustic speed heterogeneity. Not
      requiring the prior knowledge of the acoustic speed distribution like most other
      algorithms, this algorithm utilizes the correlation information between
      thermoacoustic signals to compensate for the acoustic heterogeneity. The absorbed
      energy density is reconstructed on the basis of a corrected time-domain formula.
      Computer simulations are carried out to validate the algorithm. It is shown that
      the algorithm has a good precision within the acoustic speed variation of 10%,
      strong robustness to random data noises and good computational efficiency
      compared to other model-based methods. Therefore, the algorithm may be used in
      TAT of biological soft tissues, in which the acoustic speed variation is normally
      within 10%.

PMID- 18711250
TI  - On the impact of longitudinal breathing motion randomness for tomotherapy
      delivery.
AB  - The purpose of this study is to explain the unplanned longitudinal dose
      modulations that appear in helical tomotherapy (HT) dose distributions in the
      presence of irregular patient breathing. This explanation is developed by the use
      of longitudinal (1D) simulations of mock and surrogate data and tested with a
      fully 4D HT delivered plan. The 1D simulations use a typical mock breathing
      function which allows more flexibility to adjust various parameters. These
      simplified simulations are then made more realistic by using 100 surrogate
      waveforms all similarly scaled to produce longitudinal breathing displacements.
      The results include the observation that, with many waveforms used
      simultaneously, a voxel-by-voxel probability of a dose error from breathing is
      found to be proportional to the realistically random breathing amplitude relative
      to the beam width if the PTV is larger than the beam width and the breathing
      displacement amplitude. The 4D experimental test confirms that regular breathing
      will not result in these modulations because of the insensitivity to leaf motion
      for low-frequency dynamics such as breathing. These modulations mostly result
      from a varying average of the breathing displacements along the beam edge
      gradients. Regular breathing has no displacement variation over many breathing
      cycles. Some low-frequency interference is also possible in real situations. In
      the absence of more sophisticated motion management, methods that reduce the
      breathing amplitude or make the breathing very regular are indicated. However,
      for typical breathing patterns and magnitudes, motion management techniques may
      not be required with HT because typical breathing occurs mostly between
      fundamental HT treatment temporal and spatial scales. A movement beyond only
      discussing margins is encouraged for intensity modulated radiotherapy such that
      patient and machine motion interference will be minimized and beneficial
      averaging maximized. These results are found for homogeneous and longitudinal on
      axis delivery for unplanned longitudinal dose modulations.

PMID- 18711252
TI  - A multi-dimensional approach for describing internal bleeding in an artery:
      implications for Doppler ultrasound guiding HIFU hemostasis.
AB  - Doppler ultrasound has shown promise in detecting and localizing internal
      bleeding. A mathematical approach was developed to describe the internal bleeding
      of the injured artery surrounded by tissue. This approach consisted of a two
      dimensional (2D) model describing the injured vessel and a one-dimensional model
      (1D) mimicking the downstream of the vessel system. The validity of this approach
      was confirmed by both the numerical simulation and in vivo measurement of a
      normal porcine femoral artery. Furthermore, the artery was injured using a 16
      gauge needle to model a penetrating injury. The velocity waveform at the puncture
      site was modeled and compared with those at the upstream and downstream of the
      artery. The results demonstrated that there was a significant increase in
      magnitude and a phase lag for the peak systolic velocity at the injury site.
      These results were qualitatively in agreement with the in vivo experiment. Flow
      turbulence indicated by this approach was also observed in a color Doppler image
      in the form of a checkered color pattern. This approach might be useful for
      quantitative internal bleeding detection and localization. Also, the phase lag of
      the peak systolic velocity was indicated to be potential in the application of
      internal bleeding detection.

PMID- 18711253
TI  - Advanced processing routes for tissue engineering and regenerative medicine.

PMID- 18711254
TI  - What is the use of routine endotracheal surveillance cultures in ventilated
      patients?

PMID- 18711255
TI  - Usage of intra-aortic balloon pump in high risk coronary artery bypass graft
      surgery.

PMID- 18711256
TI  - Role of quantitative endotracheal aspirate and cultures as a surveillance and
      diagnostic tool for ventilator associated pneumonia: a pilot study.
AB  - BACKGROUND: Accurate diagnosis and appropriate treatment of ventilator associated
      pneumonia (VAP) is crucial for good outcomes. Endotracheal suctioning is
      performed in ventilated patients as part of routine care and for tracheal
      toileting. AIM: We evaluated if quantitative endotracheal aspirate (ETA) was a
      suitable alternative to bronchoalveolar lavage (BAL) for suspected VAP. In
      addition we assessed if surveillance ETA guided antibiotic selection for
      subsequent VAP. SETTING AND DESIGN: Prospective study in the surgical intensive
      care unit (ICU) of a tertiary hospital in India. MATERIALS AND METHODS: Two
      hundred consecutive patients with mean (standard deviation) APACHE II score of
      12.3+/-5 and requiring mechanical ventilation beyond 48 hours underwent
      surveillance ETA cultures. A second ETA and BAL were performed if the patient
      developed features of VAP. The threshold for microbiological diagnosis of VAP was
      taken as 10 5 colony forming units/ml (cfu/ml) for ETA and 10 4 cfu/ml for BAL.
      STATISTICAL ANALYSIS: The sensitivity and specificity of surveillance and
      concurrent ETA aspirate cultures were compared with BAL cultures. RESULTS: VAP
      was suspected clinically and corroborated radiologically in 27/177 patients
      (15.3%). Although microbiological support for VAP was obtained by ETA in 19
      patients, bronchoscopy was possible only in 13 patients, 8 of whom had isolates
      at significant threshold. Of the 16 organisms isolated from BAL, 11 were of
      significant threshold with 9/11 (82%) BAL isolates having a similar antibiogram
      to a concurrent ETA. Only one BAL isolate (9%), at significant threshold, was not
      isolated on a concurrent ETA. On the other hand just 6/11 BAL isolates (55%) had
      an identical antibiogram to surveillance ETA. BAL had 3 additional isolates (27%)
      at significant threshold not isolated on surveillance ETA. CONCLUSIONS:
      Concurrent quantitative ETA could substitute BAL cultures for VAP. Surveillance
      ETA at 48 hours of ventilation does not appear to assist with antibiotic
      selection for a subsequent VAP.

PMID- 18711257
TI  - Coronary artery bypass grafting in patients with low ejection fraction: the
      effect of intra-aortic balloon pump insertion on early outcome.
AB  - BACKGROUND: Survival benefit with intra-aortic balloon pump (IABP) insertion for
      coronary artery bypass grafting (CABG) patients with left ventricular dysfunction
      is controversial. The aim of this study was to assess the early results of CABG
      that predict 30-day mortality and prolonged length of hospital stay (LOS) after
      isolated CABG and the role of IABP application as a main predictor in patients
      with an ejection fraction (EF) of 30% or less. MATERIALS AND METHODS: Eight
      hundred and thirty-three patients who underwent isolated CABG with EF < or = 30%
      were entered and compared with 10881 patients with EF > 30% as the control group.
      Demographic and clinical characteristics and postoperative complications were
      considered. Data were analyzed using the student's t-test and chi-square test for
      univariate analysis and the analysis of covariance and logistic regression for
      multivariate analysis. RESULTS: The thirty-day mortality rate (1.6% vs. 0.7%, P P
      P = 0.002) and prolonged LOS (P = 0.009). Also, urinary tract infection,
      prolonged ventilation, and renal failure as postoperative complications were
      statistically more in the group with the application of IABP. CONCLUSION: Low
      ejection fraction can positively affect thirty-day mortality and prolonged LOS
      and ICU stay in patients who undergo CABG. In these patients, IABP insertion is a
      strong predictor for early complication and mortality.

PMID- 18711258
TI  - Tumor necrosis factor--alpha and transforming growth factor--beta1 polymorphisms
      in bronchial asthma.
AB  - BACKGROUND: Bronchial asthma is a complex genetic disorder regulated by the
      release of cytokines and inflammatory mediators. Tumor necrosis factor alpha (TNF
      alpha) and transforming growth factor beta (TGF-beta1) cytokines play pivotal
      roles in the inflammatory response of the airways. Differential production of
      these two cytokines is associated with allelic variations in the transcriptional
      regulatory region of these genes. AIMS: The objective of the present study was to
      investigate G-308A TNF-alpha and C-509T TGF- beta1 polymorphisms for their
      association with Bronchial Asthma. MATERIALS AND METHODS: DNA isolated from 123
      asthmatics and 100 normal healthy controls were screened for these polymorphisms
      using the amplification refractory mutation system-polymerase chain reaction
      (ARMS-PCR) methods, developed in our laboratory. RESULTS: Significant allelic
      association was observed between G-308A TNF-alpha polymorphism and asthma (P =
      0.031) while no association was observed with C-509T TGF- beta1 polymorphism (P =
      0.207). Further sub-grouping based on either allergic response or family history
      failed to reveal any statistical significance among the groups or with controls.
      The interaction between these polymorphisms revealed statistically significant
      association between the high producer genotype alleles of TNF-alpha and TGF-beta
      (A/T) and asthma (P = 0.016). CONCLUSIONS: The present study reports, for the
      first time, the role of two polymorphisms, in concert, for their association with
      asthma in an Indian population. Our study supports the findings that the G-308A
      TNF-alpha promoter polymorphism is a risk factor for asthma and furthermore
      suggests that the patients with high producer alleles for TNF-alpha (-308) and
      TGF-beta (-509) have the highest risk of getting this disease in the Punjabi
      population.

PMID- 18711259
TI  - Healthcare-seeking behavior after seizures in children.
AB  - BACKGROUND: Hardly any Indian data is available regarding practices employed by
      parents for preventing injuries and aspiration and controlling convulsions in
      children. AIMS: To describe the health care-seeking behavior and practices
      employed by parents when a child has convulsions. SETTINGS AND DESIGN:
      Prospective questionnaire-based study in a tertiary care hospital setting.
      MATERIALS AND METHODS: Parents of children (age: 1 month -12 years) admitted with
      history of convulsions were enrolled and information regarding demographic
      characteristics, time lag, preferred health care provider and measures taken in a
      convulsing child was elicited using a pretested questionnaire. STATISTICAL
      ANALYSIS USED: Demographic parameters and measures employed described as
      percentages. RESULTS: One hundred and forty parents were interviewed. Seventy-six
      children had first episode. Forty-nine of 64 children with subsequent seizures
      had contact with a health care provider during the previous seizure episode. The
      median duration of seizures was 10 minutes (Mean: 54.15+/-366.39 min); but
      children were brought to the hospital after a median of 2 hours (Mean: 5.22+/
      10.37 h). Measures such as smelling onions, oral administration of cold water,
      reading religious texts and insertion of mouth gag were employed. Although 45
      with previous seizure-related health care contact agreed that they were informed
      about measures to be taken, none of them could remember more than one measure for
      preventing injuries and aspiration and controlling seizures. Only four narrated
      "per-rectal administration of diazepam" as a measure, although only one
      implemented it. Only four general practitioners used per-rectal diazepam to
      control seizures. CONCLUSIONS: Children with seizures reach health care providers
      after a considerable delay putting them at higher risk for developing
      neurological sequel. There is a need to develop appropriate strategies for
      disseminating information about "first aid" measures and steps for controlling
      convulsions and imparting relevant skills to parents.

PMID- 18711260
TI  - Spectrum and analysis of bone marrow findings in anemic cases.

PMID- 18711261
TI  - Comparative evaluation of intensive pulse polio immunization in district Valsad
      in the year 2007 and 2008.

PMID- 18711262
TI  - Human immunodeficiency virus and the ophthalmologist.

PMID- 18711263
TI  - Introduction and immunopathogenesis of acquired immune deficiency syndrome.
AB  - India has a large number of patients with acquired immune deficiency syndrome
      (AIDS), the third largest population of this group in the world. This disease was
      first described in patients with Pneumocystis pneumonia in 1981. Ocular lesions
      can occur at any stage of the disease but are more commonly seen at the late
      stages. Human immunodeficiency virus (HIV), the causative agent of AIDS is a
      retrovirus with RNA genome and a unique 'Reverse transcriptase enzyme' and is of
      two types, HIV-1 and 2. Most human diseases are caused by HIV-1. The HIV-1
      subtypes prevalent in India are A, B and C. They act predominantly by reducing
      the CD4+ cells and thus the patient becomes susceptible to opportunistic
      infections. High viral titers in the peripheral blood during primary infection
      lead to decrease in the number of CD4+ T lymphocytes. Onset of HIV-1-specific
      cellular immune response with synthesis of HIV-1 specific antibodies leads to the
      decline of plasma viral load and chronification of HIV-1 infection. However, the
      asymptomatic stage of infection may lead to persistent viral replication and a
      rapid turnover of plasma virions which is the clinical latency. During this
      period, there is further decrease in the CD4+ counts which makes the patient's
      immune system incapable of controlling opportunistic pathogens and thus life
      threatening AIDS-defining diseases emerge. Advent of highly active antiretroviral
      treatment (HAART) has revolutionized the management of AIDS though there is
      associated increased development of immune recovery uveitis in a few of these
      patients.

PMID- 18711264
TI  - Anterior segment manifestations of human immunodeficiency virus/acquired immune
      deficiency syndrome.
AB  - Ocular complications are known to occur as a result of human immunodeficiency
      virus (HIV) disease. They can be severe leading to ocular morbidity and visual
      handicap. Cytomegalovirus (CMV) retinitis is the commonest ocular opportunistic
      infection seen in acquired immune deficiency syndrome (AIDS). Though posterior
      segment lesions can be more vision-threatening, there are varied anterior segment
      manifestations which can also lead to ocular morbidity and more so can affect the
      quality of life of a HIV-positive person. Effective antiretroviral therapy and
      improved prophylaxis and treatment of opportunistic infections have led to an
      increase in the survival of an individual afflicted with AIDS. This in turn has
      led to an increase in the prevalence of anterior segment and adnexal disorders.
      Common lesions include relatively benign conditions such as blepharitis and dry
      eye, to infections such as herpes zoster ophthalmicus and molluscum contagiosum
      and malignancies such as squamous cell carcinoma and Kaposi's sarcoma. With the
      advent of highly active antiretroviral therapy, a new phenomenon known as immune
      recovery uveitis which presents with increased inflammation, has been noted to be
      on the rise. Several drugs used in the management of AIDS such as nevirapine or
      indinavir can themselves lead to severe inflammation in the anterior segment and
      adnexa of the eye. This article is a comprehensive update of the important
      anterior segment and adnexal manifestations in HIV-positive patients with special
      reference to their prevalence in the Indian population.

PMID- 18711265
TI  - Posterior segment manifestations of human immunodeficiency virus/acquired immune
      deficiency syndrome.
AB  - Ocular manifestations can occur in up to 50% of human immunodeficiency virus
      (HIV)/acquired immune deficiency syndrome (AIDS) patients and posterior segment
      involvement is the most common presentation. The posterior segment manifestations
      of AIDS can be divided into four categories: retinal vasculopathy, opportunistic
      infections, unusual malignancies and neuro-ophthalmologic abnormalities. Retinal
      microvasculopathy and cytomegalovirus (CMV) retinitis are the most common
      manifestations, even in the era of highly active anti-retroviral therapy (HAART).
      Highly active anti-retroviral therapy has been shown to cause regression of CMV
      retinitis, reduce the incidence of CMV-related retinal detachments, and prolong
      patient survival. Immune recovery uveitis is a new cause of vision loss in
      patients on HAART. Diagnosis and treatment are guided by the particular
      conditions and immune status of the patient.

PMID- 18711266
TI  - Medical management of human immunodeficiency virus infection.
AB  - The human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome
      (AIDS) pandemic has pervasive effects on culture, economics, policy, and human
      development. All organs can be affected by complications of HIV/AIDS, including
      the eye. When sufficient resources are available and widespread antiretroviral
      resistance does not exist, the four available classes of antiretroviral agents -
      nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse
      transcriptase inhibitors, protease inhibitors, and fusion inhibitors - can be
      combined to provide highly active antiretroviral therapy (HAART). For many (not
      all) patients, HAART converts an inexorably fatal disease into a chronic disease
      with a fairly good prognosis. Use of HAART often induces partial immune recovery,
      which has predominantly beneficial effects on ocular complications of AIDS.
      However, HAART-induced immune recovery sometimes results in immune recovery
      inflammatory syndromes, such as immune recovery uveitis. Use of HAART is the
      single most useful intervention for most patients with ocular complications of
      AIDS. However, specific ocular therapy is also critical to avoid blindness in the
      early months before immune recovery can occur, or if HAART is unavailable.
      Increasing availability of HAART worldwide shows great promise to alleviate one
      of the world's greatest plagues. However, predictable secular trends in the AIDS
      epidemic make it likely that the number of cases of ocular complications of AIDS
      will increase substantially before they decrease. Ophthalmologists worldwide
      should be familiar with the diagnosis and management of cytomegalovirus retinitis
      - the most common ocular complication of AIDS - and should establish partnerships
      with physicians who are able to provide HAART. Research is needed to determine
      the optimal approach for managing cytomegalovirus retinitis in resource
      constrained settings.

PMID- 18711267
TI  - Impact of highly active antiretroviral therapy on ophthalmic manifestations in
      human immunodeficiency virus / acquired immune deficiency syndrome.
AB  - Highly active antiretroviral therapy (HAART) has changed the face of human
      immunodeficiency virus (HIV) acquired immune deficiency syndrome (AIDS) by
      leading to dramatic decreases in HIV-related morbidity and mortality in the
      developed as well as developing world. Since the introduction of HAART, the
      incidence of ocular opportunistic infections causing retinitis has dramatically
      decreased, and clinicians should be aware of changes in the clinical presentation
      of ocular manifestations of HIV. As studies of HIV disease after the introduction
      of HAART continue to become available, more thorough descriptions of treated
      patients with ocular opportunistic infections will include side-effects and
      toxicities of therapy. This review focuses on the impact of HAART on the ocular
      manifestations of HIV.

PMID- 18711268
TI  - The socioeconomic impact of human immunodeficiency virus / acquired immune
      deficiency syndrome in India and its relevance to eye care.
AB  - Human immunodeficiency virus (HIV) infection is aptly called the modern day
      'plague' and has the potential to decimate people in the productive age group. On
      the other hand, the increasing life expectancy in developing countries spirals
      age-related blindness. One therefore reduces economic productivity while the
      other increases economic dependency. Both lead to increased expenditure of
      households though in different proportions. Human immunodeficiency virus and
      blindness are both associated with discrimination, stigma and long-term
      consequences. They impact the socioeconomic fabric of the affected individuals,
      communities and countries. The loss in productivity and the cost of support to
      the affected individuals are seen in both. Each is a potent problem on its own
      but together they spell disaster in geometric proportions rather than a simple
      additive effect. Strategies need to be evolved to provide solace and improve the
      quality of life of an HIV-positive blind individual.

PMID- 18711269
TI  - Efficacy of intraoperative vancomycin in irrigating solutions on aqueous
      contamination during phacoemulsification.
AB  - PURPOSE: To study the efficacy of adding vancomycin in irrigating solutions, in
      comparison to topical antibiotic given preoperatively for a day, during
      phacoemulsification, in reducing the anterior chamber (AC) contamination.
      SETTINGS AND DESIGN: This was a prospective, interventional, hospital-based
      study. MATERIALS AND METHODS: This was a study involving 400 eyes of 400 paitens,
      undergoing routine phacoemulsification between January 2004 and June 2006. The
      patients were non-randomly assigned to two groups: Group 1 included 180 patients,
      who received topical ciprofloxacin eye-drops (four-hourly) for a day
      preoperatively and Group 2 included 220 patients, who underwent
      phacoemulsification with vancomycin (20 microg/ml) in the irrigating solution.
      Anterior chamber aspirate obtained at the end of the surgery was sent for
      microbial workup. The number of positive cultures in both the groups was
      determined. STATISTICAL ANALYSIS: This was performed using Chi-square test.
      RESULTS: Aqueous samples showed microbial growth in 38 (21.1%) out of 180 eyes in
      Group 1 and in 17 (7.7%) out of 220 eyes in Group 2 ( P = 0.001). Coagulase
      negative staphylococcus was the most common organism in both the groups. Aqueous
      samples from four eyes in group 1 showed multiple organisms, while none of the
      sample from group 2 showed more than one organism. None of the eyes in either
      group showed fungal contamination. One patient in Group 1 developed
      endophthalmitis, and the causative organism was Alcaligenes faecalis. All
      patients were followed up for a minimum of six months (range: 6 to 14 months and
      mean: 9.3 months). CONCLUSION: Addition of vancomycin in irrigating solutions is
      more efficacious in reducing AC contamination in comparison to topical antibiotic
      administered a day preoperatively.

PMID- 18711271
TI  - Which is the best method to learn ophthalmology? Resident doctors' perspective of
      ophthalmology training.
AB  - The study aimed to gauge ophthalmology resident doctors' perception of their
      teaching programs and various methods used in it and to formulate a well
      structured program for teaching ophthalmology. Closed ended and open-ended
      questionnaires were used for survey of ophthalmology residents in West
      Maharashtra, India. Sixty-seven out of 69 residents of seven residency programs
      completed the questionnaire. On a scale of 0 (most unsatisfactory) to 4 (best),
      lectures with power point presentation had a median score of 4, didactic lectures
      2, seminar 3, case presentation 4, wet lab 3 and journal club 3. There was a
      discrepancy in the actual number of surgeries performed by the resident doctors
      and their perception of the number needed to master those surgeries.
      Phacoemulsification and non-cataract surgery training was neglected in most
      programs. The residents wanted to be evaluated regularly and taught basic
      ophthalmic examination, use of equipments and procedures in greater depth.

PMID- 18711270
TI  - How to prevent endophthalmitis in cataract surgeries?
AB  - Postoperative endophthalmitis is a very devastating complication and every step
      should be taken to reduce its occurrence. Unattended air conditioning filter
      systems are often the culprits and regular maintenance of the filters is of
      paramount importance. Shedders of pathogenic organisms amongst the theater
      personnel should be identified by regular screening and should be promptly
      treated. In addition to the use of Povidone iodine 5% solution in the
      conjunctival sac few minutes prior to surgery, proper construction of wound,
      injectable intraocular lenses, use of prophylactic intracameral antibiotics or
      prophylactic subconjunctival antibiotic injection at the conclusion of cataract
      surgery, placing a patch after the surgery for at least 4 h and initiating
      topical antibiotics from the same day of surgery helps to lower the frequency of
      postoperative endophthalmitis. Intraoperative posterior capsule rupture and
      anterior vitrectomy are risk factors for acute endophthalmitis, and utmost care
      to prevent posterior capsular rent should be taken while performing cataract
      surgery. Also, in case of such complication, these patients should be closely
      monitored for early signs of endophthalmitis in the postoperative period. In the
      unfortunate event of endophthalmitis the diagnosis should be prompt and treatment
      must be initiated as early as possible.

PMID- 18711272
TI  - An unusual variation in the anatomy of the uncinate process in external
      dacryocystorhinostomy.
AB  - Variations in the bony components of the nose are often encountered. One such
      variation was found in a 49-year-old male who had undergone conventional external
      dacryocystorhinostomy for adult onset nasolacrimal duct blockage.
      Intraoperatively, a thick bar of bone was seen beneath and parallel to the
      lacrimal sac fossa after a complete osteotomy had been made. Another osteotomy
      had to be fashioned in this bone to reach the nasal cavity. Postoperative 3D
      computed tomographic scan revealed the bone to be an anatomical variation of the
      uncinate process of the ethmoidal bone which was rather anteriorly placed, much
      thicker than usual, and attached to the nasal roof. The uncinate process is thin,
      curved and its anterior edge may frequently overlap some part of the lacrimal
      fossa. However, to our knowledge, the presence of such a large and thick uncinate
      process necessitating an additional large osteotomy has not been reported.

PMID- 18711273
TI  - Histopathological study of ocular erythema nodosum leprosum and post-therapeutic
      scleral perforation: a case report.
AB  - Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae ,
      clinically present either as tuberculoid, borderline or lepromatous type.
      Erythema nodosum leprosum (ENL) is an acute humoral response in the chronic
      course of lepromatous leprosy. Although very severe ENL reactions are known in
      systemic leprosy, such severity is rare in ocular tissues. A leprosy uveitis
      patient suffered from a severe form of post-therapeutic ENL reaction which
      resulted in perforation of the globe at the site of preexisting subconjunctival
      leproma. Painful blind eye was enucleated. Histopathological study revealed
      infiltration of numerous polymorphs and macrophages packed with acid-fast bacilli
      in the conjunctiva, cornea, ciliary body, ora serrata and sclera. A profuse
      influx of neutrophils on a background of macrophages packed with M. leprae
      confirmed the ocular ENL reaction. This case is reported to alert the
      ophthalmologists to a rare ocular complication of ENL.

PMID- 18711274
TI  - Lateral fixation of sclera to the periosteum with medial rectus disinsertion for
      severe myopic strabismus fixus.
AB  - Myopic strabismus fixus is characterized by severe ocular motility restriction
      with the development of progressive esotropia and hypotropia. Management of
      severe cases with strongly positive forced duction test can be challenging. We
      describe a longstanding case of myopic strabismus fixus, which was managed by
      bilateral medial rectus disinsertion and scleral fixation laterally to the
      periosteum.

PMID- 18711275
TI  - Orbital amelanotic melanoma in xeroderma pigmentosum: a rare association.
AB  - Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder of DNA
      repair in which the body's normal ability to repair damage caused by ultraviolet
      light is deficient. This leads to a 1000-fold increased risk of cutaneous and
      ocular neoplasms. Ocular neoplasms occurring in XP in order of frequency are
      squamous cell carcinoma, basal cell carcinoma and melanoma. Malignant melanomas
      occur at an early age in patients with XP. We report a case of XP with massive
      orbital melanoma in an eight-year-old boy which is unique due to its amelanotic
      presentation confirmed histopathologically.

PMID- 18711276
TI  - Retinal pigment epithelial atrophy following indocyanine green dye-assisted
      surgery for serous macular detachment.
AB  - To report subretinal migration of indocyanine green dye (ICG) and subsequent
      retinal pigment epithelial (RPE) atrophy during macular surgery for serous
      macular detachment. A 65-year-old woman presented with residual epiretinal
      membrane and serous detachment of the macula following vitreoretinal surgery for
      epiretinal membrane. She underwent resurgery with ICG-assisted internal limiting
      membrane peeling and intraocular tamponade. Intraoperatively a large area of
      subretinal ICG was seen with subsequent RPE mottling and atrophy of the macula in
      the area involved during follow-up. This case demonstrates that subretinal
      migration of ICG is possible and can be toxic to RPE.

PMID- 18711277
TI  - Intraocular tissue migration of silicone oil after silicone oil tamponade: a
      histopathological study of enucleated silicone oil-filled eyes.
AB  - Retrospective clinical and histopathological review of eight silicone oil-filled
      enucleated eyeballs using light microscopy was carried out in our department of
      ocular pathology during a period of six years. In all cases, silicone oil
      vacuoles, both free and incorporated within macrophages were seen in all the
      retinal layers. Silicone oil vacuoles were seen in the optic nerve, choroid,
      retinal pigment epithelium, corneal stroma, iris and ciliary body stroma,
      preretinal and subretinal membranes and retro-corneal membranes. Silicone oil
      migration could be seen in intraocular tissues as early as two months post
      surgery. There was no definite histopathological correlation between duration of
      tamponade and distribution of silicone oil vacuoles. Silicone oil vacuoles were
      seen in the optic nerve in eyes with neovascular glaucoma. Chronic inflammatory
      reaction was observed in the retinal tissue in the vicinity of silicone oil
      vacuoles.

PMID- 18711278
TI  - Bovine pericardium in treating large corneal perforation secondary to alkali
      injury: a case report.
AB  - To describe use of a locally processed bovine pericardium (BP) to cover a large
      central corneal perforation following alkali injury and discuss postoperative
      outcome. A 27-year-old Malay male patient presented two weeks after alkali
      splashed in his left eye while working. A clinical diagnosis of left central
      corneal ulcer with limbal ischemia following alkali injury with secondary
      infection was made. After failed medical therapy, we performed a Gunderson
      conjunctival flap under local anesthesia that retracted after one week and
      resulted in a large central corneal perforation with surrounding stromal
      thinning. The perforation was covered with a locally processed BP xenograft
      (Lyolemb) supplied by the National Tissue Bank, University Sains Malaysia. Nine
      months follow-up showed a well-taken graft without any exposure/dehiscence and
      minimal inflammation. Amniotic membrane transplantation when used as a patch
      graft needs an urgent tectonic graft to promote corneal stability in patients
      with severe corneal thinning. The use of processed BP can be a viable option in
      treating such cases.

PMID- 18711279
TI  - Familial unilateral Brown syndrome.
AB  - We present a two-generation family with Brown syndrome. The proband was a six and
      a half-year-old female who presented with a history of failure of dextro
      elevation of her left eye. A full ophthalmic evaluation was consistent with a
      left Brown syndrome. Family history revealed that her mother was operated on as a
      child for left Brown syndrome and examination of her four and a half-year-old
      sibling showed similar affection in the left eye. Autosomal dominant inheritance
      has been postulated in this condition. To our knowledge this is the first report
      of three members of a two-generation family with left-sided Brown syndrome.
      Genetic counseling of Brown syndrome cases is advised; nevertheless,
      identification of the responsible gene should shed more light on its genetics.

PMID- 18711280
TI  - An unusual ocular presentation of acquired immune deficiency syndrome.
AB  - A 50-year-old male who presented with bilateral keratomalacia and on subsequent
      evaluation was found to be human immunodeficiency virus (HIV) positive is being
      reported. A MEDLINE search of the literature did not reveal any report of
      keratomalacia as the initial presenting feature of HIV/ acquired immune
      deficiency syndrome.

PMID- 18711281
TI  - Management of intralenticular caterpillar setae.

PMID- 18711282
TI  - Combined photodynamic therapy and intravitreal ranibizumab as primary treatment
      for choroidal neovascularization associated with age-related macular degeneration
      in an Indian patient.

PMID- 18711283
TI  - Contact allergic dermatitis and periocular depigmentation after using olapatidine
      eye drops.

PMID- 18711284
TI  - Diabetic retinopathy: new proposed classification.

PMID- 18711286
TI  - Acute kidney injury due to rhabdomyolysis.
AB  - Rhabdomyolysis is a clinical and biochemical syndrome that occurs when skeletal
      muscle cells disrupt and release creatine phosphokinase (CK), lactate
      dehydrogenase (LDH), and myoglobin into the interstitial space and plasma. The
      main causes of rhabdomyolysis include direct muscular injury, strenuous exercise,
      drugs, toxins, infections, hyperthermia, seizures, meta-bolic and/or electrolyte
      abnormalities, and endocrinopathies. Acute kidney injury (AKI) occurs in 33-50%
      of patients with rhabdomyolysis. The main pathophysiological mechanisms of renal
      injury are renal vasoconstriction, intraluminal cast formation, and direct
      myoglobin toxicity. Rhabdo-myolysis can be asymptomatic, present with mild
      symptoms such as elevation of muscular en-zymes, or manifest as a severe syndrome
      with AKI and high mortality. Serum CK five times higher than the normal value
      usually confirms rhabdomyolysis. Early diagnosis and saline volume expansion may
      reduce the risk of AKI. Further studies are necessary to establish the importance
      of bicarbonate and mannitol in the prevention of AKI due to rhabdomyolysis.

PMID- 18711287
TI  - Evaluation of a transplanted kidney by Doppler ultrasound.

PMID- 18711288
TI  - Prevention of staphylococcal peritonitis in CAPD patients combining ablution and
      mupirocin.
AB  - Although there has been a dramatic decrease in the incidence of peritonitis in
      continuous ambulatory peritoneal dialysis (CAPD), rates > 0.5 episodes per
      patient per year are still common, with a very high rate of relapse. The nasal,
      pharyngeal, and skin carriage of Staphylococcus aureus (S. aureus) has been
      reported to be one of the most important of predisposing factors for peritonitis.
      Mupirocin application has been introduced to combat S. aureus carriage state with
      some degree of success. To evaluate the benefits of combining ablution for prayer
      with mupirocin in eliminating the carrier state of S. aureus and thus preventing
      peritonitis in CAPD patients, we randomized prospectively 65 patients on CAPD
      into two groups; group (1) used mupirocin intranasal application alone, and group
      (2) were instructed, in addition to application of mupirocin, to perform the
      proper ablution technique. The main outcome measures were the state of nasal,
      skin and pharyngeal S. aureus carriage state, the incidence of peritonitis, and
      mal-function-free PD catheter survival. After 3 months of CAPD initiation, S.
      aureus carrier state was detected in 11 (33.3%) patients in group (1), and in 2
      (6.25%) patients in group (2) (p aureus carriers (p aureus peritonitis occurred
      in 19 occasions in 10 patients of group (1) versus 4 occasions in 3 patients of
      group (2) (p S aureus carriage and hence it decreases the incidence of continuous
      ambulatory peritoneal dialysis-associated S. aureus peritonitis.

PMID- 18711289
TI  - Successful pregnancies post renal transplantation.
AB  - To evaluate the maternal and fetal outcomes in renal transplant female recipients
      who became pregnant from 1989 to 2005 in our center, we retrospectively studied
      20 incident pregnancies in 12 renal transplant recipients; 5 (41.7 %) of them
      from living related, 4 (33.3%) from deceased, and 3 (25%) from living unrelated
      donors. The mean age at pregnancy was 30.5 +/- 4.5 years and mean interval from
      transplantation to pregnancy was 21 +/- 5.7 months with the interval was 132
      micromol/L, and another with short interval from transplantation to pregnancy UTI
      (25%), preterm delivery respectively. Gestational age at delivery was 36.3 +/-
      3.9 weeks, and mean fetal birth weight was 2349 +/- 574 gm. Apgar score was 9-10
      in all of the 20 babies, and none revealed intrauterine growth retardation or
      congenital anomalies. We conclude that consecutive pregnancies demonstrate long
      term maternal and fetal survival and function. The major risk factors are
      elevated starting serum creatinine, hypertension, and short time interval from
      transplantation to pregnancy.

PMID- 18711290
TI  - Ocular disorders in renal transplant patients.
AB  - This cross-sectional study was performed to determine ocular findings in renal
      transplant recipients and to correlate them with certain clinical characteristics
      related to transplantation. The study was performed on 150 patients who had
      received a renal transplant at least three months earlier and had serum
      creatinine levels < 3 mg/dL. All patients underwent a complete ophthalmologic
      examination. Clinical variables studied related to the transplant included cause
      of renal failure, duration of hemodialysis prior to transplantation and
      immunosuppressive regimen. Overall, 91 male and 59 female subjects with a mean
      age of 39.9 +/- 17.7 years were included. At least one ocular abnormality could
      be detected in 89.3% including impaired visual acuity < or = 20/25 (48.6%),
      conjunctival degeneration in the palpebral fissure (36.6%), posterior sub
      capsular cataracts (24%), pinguecula (17.3%), retinal pigment epitheliopathy
      (14%), arteriovenous crossing changes (8.6%), proliferative diabetic retinopathy
      (6%), central serous chorioretinopathy and retinal vein occlusions (each in
      3.3%), and non-proliferative diabetic retinopathy, optic nerve atrophy and
      diabetic macular edema (each in 2.7%). Abnormal ocular findings were not
      correlated with the underlying renal disorder or use of cyclosporine and
      prednisolone; however, they were positively correlated with transplant duration,
      pre-transplant dialysis duration and usage of azathioprine or mycophenolate
      mofetil. Our study suggests that ocular disorders are frequent among renal
      transplant patients especially with older transplants and those with a longer
      period of pre-transplant hemodialysis.

PMID- 18711291
TI  - A clinicopathological study of lupus nephritis in children.
AB  - To assess clinical characteristics, pathological findings, and therapeutic
      response in children with lupus nephritis (LN), we retrospectively studied 25
      children under 16 years of age with LN at the Abozar children's hospital from
      1995 to 2006. The study included 13(65%) girls and 7(35%) boys. The mean age at
      the time of diagnosis of SLE was 10.2 (+/- 4.8) years. Eighteen patients (90%)
      were more than 8 years old. Sixty percent of the patients presented as nephritic
      nephrotic syndrome. All the patients underwent percutaneous renal biopsy and were
      followed up for at least 36 months. The clinical and serologic parameters at the
      time of renal biopsy were recorded. Twenty patients were treated with the
      following regimens: one (class I) with low dose prednisone, 7 (class II, III)
      with high-dose of prednisone, 12 (class IV) with high-dose prednisone plus 13
      intermittent intravenous cyclophosphamide (CTX) pulses (monthly for 6 months and
      then every 3 months), followed by mycophenolate mofetil (MMF) as maintenance
      therapy. Remission was achieved in 17 (85%) cases; one required hemodialysis and
      2 died due to renal failure and central nervous system involvement. Among 12
      cases with class IV, 11 responded to prednisone and intravenous CTX pulses. We
      conclude that i.v. pulses of CTX induced clinical remission of renal disease in
      the majority of children with severe LN. MMF maintenance therapy was effective
      after induction of remission in refractory cases. However, this study was
      performed in a small number of subjects, further studies to confirm the long-term
      efficacy and safety of CTX pulse therapy on larger numbers of patients are
      warranted.

PMID- 18711292
TI  - Association of angiotensin-converting enzyme gene dimorphisms with severity of
      lupus disease.
AB  - Angiotensin-converting enzyme (ACE) plays an important role in the development of
      systemic lupus erythematosus (SLE) because its end-product, angiotensin II, plays
      an integral role in the regulatory system responsible for endothelial control and
      vascular tone, systems that are commonly affected in patients with SLE.
      Additionally, ACE inhibitors have been shown to retard the progression of SLE and
      lupus nephritis. Our goal was to investigate whether ACE gene polymorphisms are
      associated with increasing severity of SLE. We genotyped 39 SLE patients of
      varying disease severity from a homogenous Asian population and 79 control
      subjects for ACE I/D and 2350 G > A dimorphisms. All patients met the American
      College of Rheumatology (ACR) criteria for SLE and their disease severity was
      measured using Systemic Lupus Activity Measure (SLAM). The "A" allele was found
      to be associated with increase in severity of SLE with the AA genotype present
      only in severe disease. No association with SLE in general, compared to healthy
      subjects, was found with either dimorphism. We also examined the transmission of
      haplotypes as defined by these polymorphisms. The D and A alleles were found in
      strong linkage disequilibrium especially in severe SLE. The DA-haplotype was more
      frequent in severe SLE, than mild to moderate disease. Our findings suggest that
      DNA sequence variation in the ACE gene influences disease progression and
      severity of SLE.

PMID- 18711293
TI  - Clinical and genetic mapping of X chromosome in the X-linked dominant inherited
      Alport's syndrome.
AB  - To study the hereditary mode and clinical characteristics and detect mutations of
      gene COL4A5 encoding type IV collagen a5 chain among family members of an X
      linked dominant inherited Alport's syndrome (AS) family of China, we studied all
      of 38 family members of whom 2 volunteers underwent renal biopsy. Genomic DNA
      from all members of the AS family was characterized. All of 51 exons of COL4A5
      gene were amplified by polymerase chain reaction (PCR) with the primers
      synthesized according to the published flanking intervening sequences. PCR
      products were further analyzed by agarose gel electrophoresis and single strand
      conformation polymorphism (SSCP) analysis. The study subjects revealing
      polymorphism by SSCP analysis were directly sequenced. Suspected exons were
      analyzed with reverse sequencing. Six males and 9 females of the family were
      diagnosed to have AS by clinical manifestations, family history and/or renal
      biopsy. Four patients died of end-stage renal disease (ESRD), and 1 patient
      received kidney transplantation. In the rest of the family members renal function
      remained normal, however, 22 (58%) revealed hematuria, 11/22 (59%) of them also
      had proteinuria. The hearing loss was detected in 6 (16%) and ocular lesion in 20
      (53%) of family members. By PCR-SSCP analysis, 17 PCR products were identified
      with different mobility of single strand DNA in volunteers and 9 suspected
      mutations were revealed with DNA sequencing analysis, but all of which could not
      be proven by bidirectional sequencing analysis. We conclude that the incidence of
      hematuria and ophthalmopathy is higher in the X-linked dominant inherited AS in
      this Chinese family, while some patients have isolated hematuria. Bidirectional
      sequence analysis should be taken to identify mutations of certain genes. No
      mutations were found on the region of exons of gene COL4A5.

PMID- 18711294
TI  - Effect of antiviral therapy on hepatitis C virus related glomerulopathy.
AB  - To determine the efficacy of antiviral therapy in hepatitis C virus associated
      glomerulopathy, we studied 30 patients with HCV-associated glomerulopathy at
      Sheikh Zayed Hospital, Lahore, Pakistan from June 2004 to February 2007.
      Membranoproliferative glomerulonephritis (MPGN) was the commonest kidney lesion,
      being reported in 25/30 (83%), followed by membranous glomerulonephritis (MGN) in
      3/30 (10%) and mesangioproliferative glomerulonephritis (MesGN) in 2/30 (7%).
      Cryoglobulinaemia was positive in 8/20 (40%) cases. Most common HCV genotype was
      3a. All the patients received interferon alpha combined with ribavirin therapy
      for 6-12 months based on viral genotypes and doses were adjusted according to
      renal function. Anti-viral response was achieved in the form of aviremia at
      completion of 6 months treatment in 8/30 (26.6%), decreased transaminases levels
      from a mean of 96.4 +/- 72.2 to 60.1 +/- 44.3 IU/L, p= 0.005, 24-hour proteinuria
      decreased significantly from a mean of 4.8 g to 1.20 g, p= 0.001, and complement
      C3 and C4 concentrations returned to normal in those subjects who responded to
      treatment. The rate of relapse was 50%. We conclude that though the overall
      antiviral response of HCV was not high, there was a significant reduction in
      proteinuria suggesting indirectly an improvement in renal pathology. Further
      studies with large number of patients with follow-up renal biopsies are
      warranted.

PMID- 18711295
TI  - Predicting hemodialysis access failure with the measurement of dialysis access
      recirculation.
AB  - Clinical practice guidelines recommend regular monitoring of hemodialysis (HD)
      vascular access using methods such as vascular access recirculation (AR), for
      early detection and correction of access dysfunction. We measured access
      recirculation using low blood flow method in 51 chronic HD patients. Of these
      patients, 42 had arteriovenous fistulas and nine had synthetic arteriovenous
      grafts. The mean access recirculation rate was 8.75%. We conclude that AR
      reflects the access blood flow and patients with high AR rate due to stenosis
      should be referred for intervention or revision for prolonging the life of the
      access.

PMID- 18711296
TI  - Chronic inflammation increases risk in hemodialysis patients.
AB  - Chronic inflammation is the cause of malnutrition and cardiovascular disease in
      hemodialysis patients. The purpose of this study was to assess C Reactive Protein
      (CRP) as an inflammatory marker and to define the relationship between CRP and
      other inflammatory and nutritional factors in this group of patients. One hundred
      and fourteen hemodialysis patients undergoing chronic dialysis (3 times a week
      for at least 4 hours) in two hemodialysis centers were enrolled in this cross
      sectional study. Anthropometric and laboratory data including CRP, Il-6,
      hemoglobin, serum ferritin, triglyceride, cholesterol, albumin, total protein and
      transferrin were measured. The Kt/V for adequacy of dialysis was also calculated.
      There was a statistically significant correlation between the mean CRP and
      albumin, hemoglobin, and transferrin; while such relation was not found with BMI,
      ferritin, the length of dialysis, triceps skin fold thickness, mid arm
      circumference, mid arm muscle circumference, and Kt/V. We conclude that the
      negative relationship between CRP and albumin, transferrin, and hemoglobin
      suggests a correlation between inflammatory and nutritional factors.

PMID- 18711297
TI  - Tuberculosis in a renal allograft: a successful outcome.
AB  - Tuberculosis is endemic in most South-East Asian countries including India. It
      causes significant morbidity and mortality in renal transplant recipients and
      often, it is not diagnosed early, due to its innocuous clinical presentations. A
      high index of suspicion and proactive management in the early phase of
      presentation can reduce allograft nephropathy, graft nephrectomy and mortality. A
      patient with an unusual presentation of tuberculosis localized to the allograft
      and successful management with anti-tuberculosis medications is described.

PMID- 18711298
TI  - De novo collapsing glomerulopathy in a renal allograft recipient.
AB  - Collapsing glomerulopathy (CG), characterized histologically by segmental/global
      glomerular capillary collapse, podocyte hypertrophy and hypercellularity and
      tubulo-interstitial injury; is characterized clinically by massive proteinuria
      and rapid progressive renal failure. CG is known to recur in renal allograft and
      rarely de novo. We report de novo CG 3 years post-transplant in a patient who
      received renal allograft from haplo-identical type donor.

PMID- 18711299
TI  - Vitamin D dependent rickets type II: late onset of disease and response to high
      doses of vitamin D.
AB  - Vitamin D dependent rickets Type II is a rare autosomal recessive disorder. The
      disorder is characterized by end organ hyporesponsiveness to vitamin D. Common
      presentation of the disorder is total body alopecia and onset of rickets during
      the second half of the first year of life. Patients may display progressive
      rachitic bone changes, hypocalcemia and secondary hyper-parathyroidism. It is
      differentiated from vitamin D dependent rickets type I by virtue of response to
      physiological doses of exogenous vitamin D in the later. Target organ
      hyporesponsiveness can be overcome by higher doses of vitamin D or its analogues.
      We report a case of vitamin D dependent rickets type II with onset of rickets at
      the age of thirteen years without alopecia progressing to marked disability by
      twenty three years of age. She responded to massive doses of vitamin D with
      significant clinical improvement after six months of therapy.

PMID- 18711300
TI  - Giant solitary echinococcal cyst of the seminal vesicle: an uncommon cause of
      retention of urine.
AB  - Echinococcal cysts (EC) of the retroperitoneum are a rare occurrence. Such cysts
      involving the seminal vesicle and attaining massive size are very rare. These
      cysts may remain asymptomatic for long periods or may produce nonspecific
      symptoms. We herewith present a rare case of isolated giant EC of the seminal
      vesicle, which presented as acute retention of urine. To the author's knowledge,
      such a large EC of the seminal vesicle has not been reported previously in the
      medical literature.

PMID- 18711301
TI  - Plasma cell dyscrasia; LCDD vs Immunotactoid glomerulopathy.
AB  - Light chain deposit disease is a plasma cell disorder characterized by production
      of a large amount of monoclonal immunoglobulin light chain or part of it, which
      is usually deposited as an amorphous substance in the kidneys. Immunotactoid
      glomerulopathy is an uncommon disease, which might be related to plasma cell
      dyscrasia, and characteristically manifest as organized glomerular ultra
      structural fibrils or microtubules. In this article, we report a case of a
      combined presentation of light chain disease and immunotactoid glomerulopathy in
      a patient with multiple myeloma and reversible advanced renal failure.

PMID- 18711302
TI  - Asymptomatic bilateral ureteropelvic junction obstruction due to supernumerary
      renal arteries.
AB  - A supernumerary renal artery is a common arterial variation, which warrants
      considerations in a variety of urologic and retroperitoneal operations.
      Supernumerary renal arteries can be associated with other uro-vascular variations
      and anomalies such as duplicated renal veins and ureters, aberrant origin of the
      gonadal arteries, persistence of fetal renal lobulation, and kidney malrotation.
      The role of crossing supernumerary renal arteries in ureteropelvic junction
      obstruction (UPJO) is controversial. We report a healthy potential renal
      transplant donor with bilateral UPJO, which appeared to be secondary to
      supernumerary renal (inferior polar) arteries. We believe that the bilateral
      occurrence of asymptomatic UPJO associated with supernumerary renal arteries has
      not been previously reported.

PMID- 18711303
TI  - Gastrointestinal angiodysplasia in chronic renal failure.
AB  - Gastrointestinal (GI) hemorrhage is a frequent and sometimes life-threatening
      complication of end-stage renal failure. Angiodysplasia (AD), vascular
      malformation, is the most common cause of recurrent lower-intestinal hemorrhage
      in patients with renal failure. We report four chronic hemodialysis patients with
      AD. All patients presented with severe anemia requiring transfusion. GI
      hemorrhage ceased spontaneously in three cases and after treatment with argon
      plasma coagulation in another. Diagnosis of AD is usually challenging, since its
      cause is still unknown, and its clinical presentation is variable. Lesions are
      multiple in 40-75% of cases, often located in the stomach and duodenum but can
      affect the colon and the jejunum. Diagnosis is improved by endoscopy which has a
      much higher sensitivity compared to angiography. Capsular endoscopy may reveal
      the hemorrhage site in the small intestine when regular endoscopy fails, and
      therapeutic intervention usually include argon plasma coagulation.

PMID- 18711304
TI  - Non-diabetic renal disease in diabetic patients.
AB  - The occurrence of non-diabetic renal diseases (NDRD) in diabetic patient is well
      recognized. Different frequencies for NDRD have been reported from different
      parts of the world. This is a retrospective study of 16 renal biopsies from
      diabetic patients. The biopsy samples were all examined by light,
      immunofluoresence and electron microscopy. Non-diabetic renal diseases were
      encountered in eight cases (50%). Membranous glomerulonephritis (MGN) was the
      most common NDRD seen in three of the eight cases (37.5%). Immunoglobulin A
      nephropathy (IgAN), membranoproliferative glomerulonephritis type I (MPGN) and
      postinfectious glomerulonephritis (PIGN) were seen in one case each (12.5%).
      Interstitial nephritis was seen in two cases representing 25% of NDRD. In
      conclusion, the current study demonstrates the occurrence of NDRD in diabetic
      patients and the most frequently encountered lesion was MGN. Thus, renal biopsy
      in diabetic patients may prove to be helpful in identifying an underlying NDRD
      for better management.

PMID- 18711305
TI  - Notes on HCV- ELISA test results of the hemodialysis patients.

PMID- 18711306
TI  - Sirolimus-induced aphthous ulcers which disappeared with conversion to
      everolimus.

PMID- 18711307
TI  - Oral sodium thiosulfate solution as a secondary preventive treatment for
      calciphylaxis in dialysis patients.

PMID- 18711308
TI  - Failure rate of first arterio-venous fistula in a developing country.

PMID- 18711309
TI  - Cancers after renal transplantation: multicenter experience.
AB  - Renal transplant recipients are at higher risk of certain tumors such as
      lymphomas and skin cancers and than the general and dialysis populations. We
      retrospectively studied the prevalence of tumors in adult renal transplant
      recipients in four Tunisian centers of transplantation in Tunis, Monsatir and
      Sfax from January 1986 to January 2005. The study included 36 patients; 19 men
      and 17 women with a mean age of 34.6 years (range from 18-54 years). The mean
      time since dialysis to transplantation was 43 months (6-131months). Maintenance
      therapy was based on calcineurin inhibitors (CNI) in 86 % of cases, on
      antimetabolites and corticosteroids in 100 % of cases. Anti-thymoglobulin was
      administered in a mean course of 12.4 days in 78 % of the patients. Acute
      rejection occurred in 25 cases and was treated with polyclonal or monoclonal
      antibodies on 40 % of cases. Incidence of cancer among our population was 7 % and
      occurred after a mean period of 54 months of transplantation (range from 4-160
      months). Eighty three percent of the tumors were solid, and the rest were in the
      skin. Kaposi sarcoma formed 41.6 % and non-Hodgkin or Hodgkin lymphoma 27.7 % of
      the solid tumors, while spinocellular carcinoma formed 83% and basocellular
      carcinoma 17% of the skin tumors. Switching CNI to sirolimus in 8.3% cases was
      associated with a favorable outcome. Mortality was the outcome in 33.3% of the
      patients with cancer, while partial or complete regression of cancers was
      observed in 55.5% cases after decreasing the doses of the immunosuppressive
      medications. We conclude that post renal transplant cancer is mainly
      characterized by the predominance of Kaposi sarcoma favored by solar exposure and
      rigorously induced and maintained immunosuppression. Careful follow-up may
      results in early intervention and decrease mortality.

PMID- 18711310
TI  - Living related donor kidney transplantation in Libya: a single center experience.
AB  - The aim of this study is to report the experience from a single center in Libya,
      on the prevailing live-related kidney transplantation program. The results of
      three years work on kidney transplantation at the Tripoli Central Hospital
      (National Organ Transplant Program) in Libya were evaluated. The transplant
      program was launched on 17 th August, 2004 and 135 patients have been
      transplanted since then till 17 th August, 2007. All donors and recipients were
      screened thoroughly prior to transplant and monitored closely in the post
      transplant period. Our immuno-suppressive protocol was cyclosporine-based. Among
      the 135 accepted pairs, donors and recipients were genetically-related in 133
      cases (98.5%) and emotionally-related in two others. The mean donor age was 37 +/
      9.5 years (range 18-56 years) and recipient age 37 +/- 13.6 years (range 7-67
      years). There were 95 males (70.4%) and 40 females (29.6%) among the recipients
      while among the donors, there were 102 males (75.6%) and 33 females (24.4%).
      Delayed graft function was seen in three patients (2.2%), acute rejection in six
      (4.4%), post-transplant urinary tract infection in six (4.4%), pneumonia in three
      (2.2%), ureteric kink in two (1.5%) and urine leak in four (3.0%). Graft survival
      at 36 months was 93.3% while patient survival at the same period was 96.3%. This
      report indicates that the results of our transplant program are good and
      comparable with other international programs.

PMID- 18711311
TI  - Survey of the seroprovalence of HTLV I/II in hemodialysis patients and blood
      donors in Urmia.
AB  - Human T lymphocytotropic virus HTLV is a virus from retroviridae family, and more
      than 20 million people are infected with this virus worldwide. It can cause
      leukemia/lymphoma in adults, tropical spastic paralysis, HTLV associated
      myelopathy, spastic paraparesis, tropical myelopathy (HAM/TSP), and some other
      nervous system diseases. It is transmitted by means of blood products via blood
      transfusion. In Iran, except the Great Khorasan region, none of blood products
      undergo screening for HTLV. Immunodeficiency in HD patients, results in increased
      risk of infection. The aim of this study was to determine the prevalence of anti
      HTLV-I/II antibody among hemo-dialysis patients and healthy blood donors in
      Urmia, Iran. A cross-sectional study was conducted from April 2005 to January
      2006 among healthy blood donors and in 2006 among hemodialysis patients. The
      serum of 2046 blood donors and 95 Hemodialysis patients was checked with enzyme
      linked immunosorbent assay (ELISA) for anti HTLV-I/II, and positive cases were
      confirmed by western blot. Three seropositive cases among 95 hemodialysis
      patients were detected, and only one of them was confirmed by western blot. Of
      the healthy blood donors 1910 (93.4%) were males and 136 (6.6%) were females.
      Serum of 1997 (97.6%) subjects was negative, and 49 (2.6%) cases were positive
      for HTLV by ELISA. Among the positive cases western blot confirmed only 7 (14.3%)
      persons as HTLV positive, 37 (75.5%) as negative, and 5 (10.2%) as indeterminate.
      Among the 7 positive cases 6 (85.6%) were infected with HTLV-I, and only one
      (14.3%) with HTLV-I /II infection. Total Serologic prevalence of HTLV in healthy
      blood donors was 0.34%. We conclude that such high serologic prevalence in the
      population of blood donors in Urmia city, suggests the high probability of
      transmission through blood transfusion, and therefore screening of blood donors
      for human T-lymphocyte virus is essential in this region. HD patients should be
      screened for HTLV and positive subjects should be isolated.

PMID- 18711312
TI  - Laboratory variables and treatment adequacy in hemodialysis patients in Iran.
AB  - This study aims to evaluate the laboratory variables in Iranian hemodialysis pa
      tients. We studied 338 patients in 6 dialysis centers around the country. Sixty
      four percent of the patients were anemic, and the mean of hemoglobin levels in
      the patients was 9.6 +/- 1.9 g/dL. Women had a significantly higher prevalence of
      anemia (p= 0.004); however, considering the absolute hemoglobin values, there was
      no significant difference between genders (p> 0.05). The mean urea reduction
      ratio (URR) and Kt/V in the patients were 62.6 +/- 12.8 and 1.17 +/- 0.31,
      respectively. Hyperphosphatemia and hyperkalemia were observed in 50% and 58%,
      respectively. We conclude that our study demonstrated a relatively high
      prevalence of anemia and hyper-phosphatemia, however, a surprisingly good
      dialysis urea clearance in the Iranian hemodialysis patients. We should exploit
      more effort to maintain hemoglobin and serum phosphate levels with-in the target
      ranges.

PMID- 18711313
TI  - Epidemic of chronic kidney disease in India -what can be done?
AB  - The exact prevalence of chronic kidney disease in India is not clear in the
      absence of regular national registry data and provided only by small
      observational series or rely on reports from personal experience, but the quality
      of data is quiet uneven. There are only three population based studies in India
      commenting on the magnitude of chronic kidney disease. In a prevention program
      started at community level in Chennai, the reported prevalence is 0.86% in the
      project population and 1.39% in the control region. The second study is based on
      Delhi involving 4972 urban patients. The prevalence of chronic renal failure
      (defined as serum creatinine more than 1.8 mg/dL) to be 0.79 % or 7852 per
      million/population. The third study perhaps the only longitudinal study to
      identify the incidence of end stage renal disease is based on 572,029 subjects
      residing in city of Bhopal suggests that the average crude and age adjusted
      incidence rates of end stage renal disease were 151 and 232 per million
      population respectively. The resources and skill for taking care of this large
      case load, both in terms of personal and health care infrastructure do not exist
      currently and would need to be created. To tackle the problem of limited access
      to renal replacement therapy, an important method would be to try and reduce the
      incidence of end stage renal disease and the need of renal replacement therapy by
      preventive measures. It is clear that treatment of chronic kidney disease and its
      advanced stage end stage renal disease is expensive and beyond the reach of
      average Indian. Thus it is crucial that prevention of chronic kidney disease has
      to be the goal of medical fraternity, government of India and the general public.
      This article suggests a series of primary, secondary and tertiary preventive
      measures for prevention of chronic kidney disease. Clearly there are already many
      effective and attractive interventions for the treatment and prevention of
      chronic kidney disease exist and many more surely be developed.

PMID- 18711314
TI  - Calciphylaxis after parathyroidectomy in chronic renal failure.
AB  - A 33-year-old man, who was maintained on hemodialysis for more than 9 years, was
      diagnosed to have secondary hyperparathyroidism with a nodule in a parathyroid
      gland revealed with ultrasound and CT scan. He underwent parathyroidectomy and
      presented with bilateral lower limb painful ulcers two months later. Skin biopsy
      from these ulcers was consistent with calciphylaxis.

PMID- 18711315
TI  - The cancer stem cell theory: is it correct?
AB  - The cancer stem cell hypothesis posits that tumor growth is driven by a rare
      subpopulation of cells, designated cancer stem cells (CSC). Studies supporting
      this theory are based in large part on xenotransplantation experiments wherein
      human cancer cells are grown in immunocompromised mice and only CSC, often
      constituting less than 1% of the malignancy, generate tumors. Herein, we show
      that all colonies derived from randomly chosen single cells in mouse lung and
      breast cancer cell lines form tumors following allografting histocompatible mice.
      Our study suggests that the majority of malignant cells rather than CSC can
      sustain tumors and that the cancer stem cell theory must be reevaluated.

PMID- 18711316
TI  - Cl- -channel is essential for LDL-induced cell proliferation via the activation
      of Erk1/2 and PI3k/Akt and the upregulation of Egr-1 in human aortic smooth
      muscle cells.
AB  - Low-density lipoprotein (LDL) induces cell proliferation in human aortic smooth
      muscle cells (hAoSMCs), which may be involved in atherogenesis and intimal
      hyperplasia. Recent studies have demonstrated that Cl- channels are related to
      vessel cell proliferation induced by a variety of stimuli. In this study, we
      investigated a potential role of Cl-channels in the signaling pathway of LDL
      effects on hAoSMC proliferation with a focus on the activation of Erk1/2-PI3K/Akt
      and the subsequent upregulation of Egr-1. Cl- channel blockers, DIDS, but neither
      NPPB nor Furosemide, completely abolished the LDL-induced DNA synthesis and cell
      proliferation. Moreover, DIDS, but not NPPB, significantly decreased LDL
      stimulated Cl- concentration, as judged by flow cytometry analysis using MQAE as
      a Cl- -detection dye. DIDS pretreatment completely abolished the activation of
      Erk1/2 and PI3K/Akt in a dose-dependent manner that is the hallmark of LDL
      activation, as judged by Western blot and proliferation assays. Moreover,
      pretreatment with DIDS (Cl- channel blockers) but not LY294002 (PI3K inhibitors)
      completely abolished the LDL-induced upregulation of Egr-1 to the same extent as
      PD98059 (MEK inhibitors to inhibit Erk), as judged by Western blot and luciferase
      reporter assays. This is the first report, to our knowledge, that DIDS-sensitive
      Cl- channels play a key role in the LDL-induced cell proliferation of hAoSMCs via
      the activation of Erk1/2 and PI3K/Akt and the upregulation of Egr-1.

PMID- 18711317
TI  - The vomeronasal organ and adjacent glands express components of signaling
      cascades found in sensory neurons in the main olfactory system.
AB  - The vomeronasal organ (VNO) is a sensory organ that influences social and/or
      reproductive behavior and, in many cases, the survival of an organism. The VNO is
      believed to mediate responses to pheromones; however, many mechanisms of signal
      transduction in the VNO remain elusive. Here, we examined the expression of
      proteins involved in signal transduction that are found in the main olfactory
      system in the VNO. The localization of many signaling molecules in the VNO is
      quite different from those in the main olfactory system, suggesting differences
      in signal transduction mechanisms between these two chemosensory organs. Various
      signaling molecules are expressed in distinct areas of VNO sensory epithelium.
      Interestingly, we found the expressions of groups of these signaling molecules in
      glandular tissues adjacent to VNO, supporting the physiological significance of
      these glandular tissues. Our finding of high expression of signaling proteins in
      glandular tissues suggests that neurohumoral factors influence glandular tissues
      to modulate signaling cascades that in turn alter the responses of the VNO to
      hormonal status.

PMID- 18711339
TI  - Predicting PDZ domain-peptide interactions from primary sequences.
AB  - PDZ domains constitute one of the largest families of interaction domains and
      function by binding the C termini of their target proteins. Using Bayesian
      estimation, we constructed a three-dimensional extension of a position-specific
      scoring matrix that predicts to which peptides a PDZ domain will bind, given the
      primary sequences of the PDZ domain and the peptides. The model, which was
      trained using interaction data from 82 PDZ domains and 93 peptides encoded in the
      mouse genome, successfully predicts interactions involving other mouse PDZ
      domains, as well as PDZ domains from Drosophila melanogaster and, to a lesser
      extent, PDZ domains from Caenorhabditis elegans. The model also predicts the
      differential effects of point mutations in peptide ligands on their PDZ domain
      binding affinities. Overall, we show that our approach captures, in a single
      model, the binding selectivity of the PDZ domain family.

PMID- 18711340
TI  - High-resolution metagenomics targets specific functional types in complex
      microbial communities.
AB  - Most microbes in the biosphere remain unculturable. Whole genome shotgun (WGS)
      sequencing of environmental DNA (metagenomics) can be used to study the genetic
      and metabolic properties of natural microbial communities. However, in
      communities of high complexity, metagenomics fails to link specific microbes to
      specific ecological functions. To overcome this limitation, we developed a method
      to target microbial subpopulations by labeling DNA through stable isotope probing
      (SIP), followed by WGS sequencing. Metagenome analysis of microbes from Lake
      Washington in Seattle that oxidize single-carbon (C1) compounds shows specific
      sequence enrichments in response to different C1 substrates, revealing the
      ecological roles of individual phylotypes. We also demonstrate the utility of our
      approach by extracting a nearly complete genome of a novel methylotroph,
      Methylotenera mobilis, reconstructing its metabolism and conducting genome-wide
      analyses. This high-resolution, targeted metagenomics approach may be applicable
      to a wide variety of ecosystems.

PMID- 18711341
TI  - Network-based prediction of human tissue-specific metabolism.
AB  - Direct in vivo investigation of mammalian metabolism is complicated by the
      distinct metabolic functions of different tissues. We present a computational
      method that successfully describes the tissue specificity of human metabolism on
      a large scale. By integrating tissue-specific gene- and protein-expression data
      with an existing comprehensive reconstruction of the global human metabolic
      network, we predict tissue-specific metabolic activity in ten human tissues. This
      reveals a central role for post-transcriptional regulation in shaping tissue
      specific metabolic activity profiles. The predicted tissue specificity of genes
      responsible for metabolic diseases and tissue-specific differences in metabolite
      exchange with biofluids extend markedly beyond tissue-specific differences
      manifest in enzyme-expression data, and are validated by large-scale mining of
      tissue-specificity data. Our results establish a computational basis for the
      genome-wide study of normal and abnormal human metabolism in a tissue-specific
      manner.

PMID- 18711342
TI  - The syndrome of inappropriate secretion of antidiuretic hormone associated with
      SCT: clinical differences following SCT using cord blood and BM/peripheral blood.
AB  - Previously, we reported the syndrome of inappropriate secretion of antidiuretic
      hormone (SIADH) as an underestimated complication associated with SCT. In the
      present report, we analyzed detailed data on a larger number of patients with
      SIADH following SCT and found different SIADH clinical features following cord
      blood SCT (CBSCT) and BMT/PBSCT. The median onset of SIADH following CBSCT and
      BMT/PBSCT was 19 and 46 days after SCT, respectively, and the median numbers of
      WBC at the onset of SIADH were 1.0 and 3.1 x 10(9)/l, respectively. Furthermore,
      severe symptoms such as seizures, somnolence and rigidity of limbs were observed
      only in patients with CBSCT (8/15 vs 0/10). These differences were statistically
      significant (P<0.01). Although the precise basis for SIADH following SCT still
      remains unknown, the different features of SIADH observed following CBSCT and
      BMT/PBSCT may provide important clues to the disease mechanism following SCT.
      Additionally, we confirmed our previous results that patients with SIADH showed a
      higher overall survival and event-free survival rates. However, we first
      suggested that they had some neurological disorders and that neurological
      sequelae such as developmental delay and seizures would consequently occur.

PMID- 18711343
TI  - Reduced-intensity umbilical cord blood transplant for older adult patients.

PMID- 18711344
TI  - Restoration of donor chimerism by nilotinib in a chronic myeloid leukaemia
      patient post mutation-associated imatinib mesylate resistance and allogeneic stem
      cell transplant failure.

PMID- 18711345
TI  - Quality of life and social integration after allogeneic hematopoietic SCT.
AB  - In total, 124 adult patients in remission after allogeneic hematopoietic SCT
      (HSCT) participated in a cross-sectional study to assess health-related quality
      of life (HRQL). Assessment of HRQL was carried out using two questionnaires: the
      (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy (FACT) with
      specific modules for BMT (FACT-BMT). Transplanted patients differed from healthy
      controls in many HRQL-related dimensions in the EORTC QLQ-C30: social functioning
      73.4 versus 85.8, P<0.0001; role functioning 74.6 versus 83.3, P<0.004; physical
      functioning 83.9 versus 89.9, P<0.001; emotional functioning 72.2 versus 82.8,
      P<0.0001 but were not significant for global HRQL 71.2 versus 75.3, P<0.03. In
      total, 60% of the patients returned to work after HSCT; 31% part time and 29%
      full time. Age at HSCT and employment status were significantly associated with
      HRQL. Other factors such as disease and disease stage and especially the
      occurrence of late complications did not impact the perception of HRQL. This
      study suggests that the perception of HRQL after HSCT differs from the general
      population. Issues to increase work-related capabilities and improve social
      support need to be addressed.

PMID- 18711346
TI  - 400 cGy TBI with fludarabine for reduced-intensity conditioning allogeneic
      hematopoietic stem cell transplantation.
AB  - Fludarabine and 200 cGy TBI are commonly used for reduced-intensity conditioning
      preceding allogeneic hematopoietic SCT (HSCT). However, graft rejection and
      disease relapse are significant causes of treatment failure with this regimen. We
      modified this regimen by escalating the TBI dose to 400 cGy in 40 patients with
      hematologic malignancies. Thirty-four patients achieved complete donor T-cell
      chimerism at a median of 40 days following HSCT. The incidences of grades II-IV
      and III-IV acute GVHD were 40 and 15%, respectively, whereas that of limited and
      extensive chronic GVHD were 12 and 20%, respectively. Two patients rejected their
      grafts and 12 relapsed. The 100-day mortality was 18%, 2-year transplant-related
      mortality 20% and overall survival was 58% at a median follow-up of 16 months.
      There were no significant survival differences between patients with lymphoid
      compared to myeloid malignancies. A dose of 400 cGy TBI administered with
      fludarabine is well tolerated and further study is needed to determine whether
      outcomes are superior to those with 200 cGy TBI.

PMID- 18711347
TI  - BM-derived cells randomly contribute to neoplastic and non-neoplastic epithelial
      tissues at low rates.
AB  - Epithelial cancers can arise from BM-derived cells (BMCs) in animal models. We
      studied whether the same phenomenon can occur in humans. Biopsy specimens from
      carcinomas and healthy adjacent tissues were obtained from three women who had
      undergone allogeneic BMT from an HLA-matched brother. Complete donor
      hematopoietic chimerism was verified by cytogenetic analysis, RFLP analysis or by
      reverse transcription-PCR analysis. Biopsies were studied for the presence of the
      Y chromosome derived from BM-derived cells by combined FISH and
      immunohistochemical staining. In our studies, we showed that human epithelial
      neoplastic and adjacent non-neoplastic tissues incorporate the Y chromosome at
      low and comparable rates. The lack of enrichment in malignancies argues against
      the possibility that BM-derived cells represent a direct source of carcinomas,
      and we suggest that these cells randomly contribute to neoplastic and non
      neoplastic epithelial cells. On the basis of the absence of a fusion karyotype,
      we favor a model in which the differentiation of BM-derived cells is largely
      determined by the microenvironment encountered.

PMID- 18711348
TI  - Therapeutic potential of non-adherent BM-derived mesenchymal stem cells in tissue
      regeneration.
AB  - We demonstrated that non-adherent BM cells (NA-BMCs) can be expanded in
      suspension and give rise to multiple mesenchymal phenotypes including
      fibroblastic, osteoblastic, chondrocytic and adipocytic as well as glial cell
      lineages in vitro using the 'pour-off' BMC culture method. Mesenchymal stem cells
      (MSCs) derived from NA-BMCs (NA-MSCs) from wild-type mice were transplanted into
      VDR gene knockout (VDR(-/-)) mice that had received a lethal dose of radiation.
      Results revealed that NA-MSC can be used to rescue lethally irradiated mice and
      become incorporated into a diverse range of tissues. After lethal dose
      irradiation, all untransplanted mice died within 2 weeks, whereas those
      transplanted with NA-MSCs were viable for at least 3 months. Transplantation
      rescued these mice by reconstructing a hematopoietic system and repairing other
      damaged tissues. WBC, RBC and platelet counts recovered to normal after 1 month,
      and VDR gene expression was found in various tissues of viable VDR(-/-)
      recipients. Adult BM harbors pluripotent NA-MSCs, which can migrate in vivo into
      multiple body organs. In an appropriate microenvironment, they can adhere,
      proliferate and differentiate into specialized cells of target tissues and thus
      function in damaged tissue regeneration and repair.

PMID- 18711349
TI  - G-CSF-stimulated BM progenitor cells supplement suboptimal peripheral blood
      hematopoietic progenitor cell collections for auto transplantation.
AB  - Peripheral blood hematopoietic progenitor cells (PBHC) are the standard source of
      support for high-dose chemotherapy because of faster recovery of marrow function.
      Unfortunately, a proportion of patients are unable to mobilize adequate
      progenitors to proceed to autologous hematopoietic cell transplant (AHCT).
      Granulocyte-CSF-stimulated BM-derived hematopoietic progenitor cells (BMHC) may
      circumvent this problem. From 1999 to 2006, 52 patients (cases) with AML, Hodgkin
      (HL) or non-Hodgkin's lymphoma (NHL) in whom PBHC mobilization failed underwent a
      G-CSF-stimulated bone marrow harvest and proceeded to AHCT. Their outcome was
      compared with 422 patients (controls) with AML, HL and NHL undergoing AHCT using
      only PBHC. Twenty-three patients received BMHC alone and 29 patients received a
      combination of PBHC and BMHC. Median engraftment time for neutrophils (>0.5 x
      10(9)/l) and platelets (>20 x 10(9)/l) were 14 and 27 days, but significantly
      longer when compared with controls (11 days, 11 days, P<0.0001). Patients
      receiving both PBHC and BMHC had faster engraftment, when compared with those
      receiving BMHC alone (P<0.001). In conclusion, performing an AHCT using G-CSF
      stimulated BMHC in patients failing PBHC collection is feasible with faster
      engraftment seen in patients receiving both BMHC and PBHC over BMHC alone.

PMID- 18711350
TI  - Allogeneic SCT in refractory or relapsed adult ALL is effective without prior
      reinduction chemotherapy.
AB  - We present 60 patients with refractory (n=8) or relapsed (n=52) adult ALL who
      received allogeneic hematopoietic SCT (HSCT) with (n=41) or without (n=19) prior
      reinduction chemotherapy. In our center, omission of reinduction is recommended
      if a suitable donor is promptly available, tumor burden is moderate and disease
      features suggest a highly aggressive course. Overall survival (OS) of the whole
      cohort at 1, 2 and 5 years was 42, 33 and 28%, respectively. Leukemia-free
      survival at 1, 2 and 5 years was 37, 33 and 24%. Deaths were due to relapse
      (n=25), acute or chronic GVHD (n=7), infections (n=8) or toxicity (n=4).
      Interestingly, patients who did not receive reinduction before HSCT had better
      outcomes than patients who received reinduction with OS at 1, 2 and 5 years being
      58 vs 34%, 47 vs 25% and 47 vs 18%, respectively (P=0.039). Importantly, even
      achievement of a second CR after reinduction was not associated with improved
      survival compared to patients directly proceeding to HSCT. We conclude that
      patients who undergo HSCT for refractory or relapsed ALL can achieve long-term
      survival. In selected patients, reinduction chemotherapy can be omitted if
      immediate HSCT is feasible.

PMID- 18711351
TI  - Donor lymphocyte infusions: the long and winding road: how should it be traveled?
AB  - Donor lymphocyte infusions (DLI) often are used after allo-SCT to augment the
      graft-versus-tumor effect. Timing of infusion varies according to indication, for
      example to treat tumor recurrence, as a planned strategy to prevent disease
      relapse in the setting of T-cell-depleted grafts or non-myeloablative
      conditioning regimens, or as a method to convert mixed to full donor chimerism.
      The optimal strategy of timing, use of cytotoxic conditioning, cell dose and cell
      product composition, and so on, for DLI administration remains unclear. Despite
      varied techniques, DLI may lead to 3-year disease-free survivals (DFS) in excess
      of 60% for all CML patients and approach 90% in patients with only molecular or
      cytogenetic relapse. Other hematologic malignancies appear much less responsive,
      as less than 50% of patients respond and provide, at best, 3-year DFS rates of 20
      50%. Multiple myeloma patients have overall response rates of 40-45% after DLI,
      suggesting benefit in relapsed disease, but limited experiences for diseases such
      as Hodgkin's lymphoma, myelodysplasia and ALL preclude recommendations for use of
      DLI at this time. Regardless of the indication, treatment-related mortality after
      DLI is 5-20% and more than one-third of patients will develop acute and/or
      chronic GVHD after DLI. The risks of these complications appear related, in part,
      to donor source, cell dose and therapy prior to DLI. Although there are no
      definitive answers, the information gleaned from published literature suggests
      that DLI should be administered early after relapse or as a prophylactic strategy
      in patients receiving T-cell-depleted grafts, and patients with bulky or
      aggressive disease may benefit from disease reduction prior to DLI.

PMID- 18711352
TI  - Feasibility of conditioning with thymoglobulin and reduced intensity TBI to
      reduce acute GVHD in recipients of allogeneic SCT.
AB  - Murine studies using anti-T-cell antibodies for conditioning in allogeneic SCT
      demonstrate engraftment with low rates of GVHD. On the basis of this preclinical
      model, we conditioned 30 patients with advanced hematologic malignancies with
      rabbit antithymocyte globulin (ATG) and TBI, to reduce rates of fatal acute GVHD.
      Patients were enrolled in two sequential groups: cohort 1 received ATG 10 mg/kg
      in divided doses (days -4 to -1)+200 cGy TBI (n=16), and cohort 2 received ATG
      (days -10 to -7)+450 cGy TBI (n=14). Median donor blood chimerism for the
      combined group was 94, 93 and 93% in the first, second and third months after
      transplant. Only three developed grade II acute GVHD despite 43% of patients
      receiving unrelated donor transplants. One-year survival was 71+/-11 and 54+/
      14%, respectively, in recipients of related and unrelated donor SCT. Donor
      lymphocyte infusions were needed in 12 patients for the management of relapse and
      for mixed donor-recipient chimerism in 4 patients. We conclude that 10 mg/kg ATG
      and TBI allows engraftment with a low risk of acute GVHD; however, further dose
      optimization of ATG is required to achieve a balance between GVHD and disease
      relapse.

PMID- 18711353
TI  - Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and
      may contribute to early neoplastic transformation.
AB  - Patients with inflammatory bowel disease (IBD) are at increased risk of
      developing colorectal adenocarcinoma. The factors that result in IBD-associated
      carcinogenesis are not understood. We hypothesized that altered expression of
      intestinal epithelial tight junction proteins might contribute to neoplastic
      progression. Semiquantitative immunohistochemical staining of human biopsies was
      used to assess expression of the tight junction proteins claudin-1, claudin-2,
      claudin-4, and occludin in IBD, IBD-associated dysplasia, acute, self-limited
      colitis (ASLC), and sporadic adenomas. Claudin-1 and claudin-2 expression was
      elevated in active IBD, adenomas, and IBD-associated dysplasia, but not ASLC. In
      contrast, claudin-4 expression was elevated in both active IBD and ASLC. Occludin
      expression was similar to control in all cases. Importantly, in IBD, claudin-1
      and claudin-2 expression correlated positively with inflammatory activity. To
      investigate mechanisms underlying altered claudin expression, beta-catenin
      activation was assessed as nuclear localization. Like claudin-1 and claudin-2,
      beta-catenin was markedly activated in IBD, sporadic dysplasia, and IBD
      associated dysplasia, but was only slightly activated in ASLC. Taken together,
      these data suggest that beta-catenin transcriptional activity is elevated in
      chronic injury and that this may contribute to increased claudin-1 and claudin-2
      expression. We speculate that increased claudin-1 and claudin-2 expression may be
      involved at early stages of transformation in IBD-associated neoplasia.

PMID- 18711355
TI  - Immunoglobulin derived depositions in the nervous system: novel mass spectrometry
      application for protein characterization in formalin-fixed tissues.
AB  - Proteinaceous deposits are occasionally encountered in surgically obtained
      biopsies of the nervous system. Some of these are amyloidomas, although the
      precise nature of other cases remains uncertain. We studied 13 cases of
      proteinaceous aggregates in clinical specimens of the nervous system. Proteins
      contained within laser microdissected areas of interest were identified from
      tryptic peptide sequences by liquid chromatography-electrospray tandem mass
      spectrometry (LC-MS/MS). Immunohistochemical studies for immunoglobulin heavy and
      light chains and amyloidogenic proteins were performed in all cases.
      Histologically, the cases were classified into three groups: 'proteinaceous
      deposit not otherwise specified' (PDNOS) (n=6), amyloidoma (n=5), or
      'intracellular crystals' (n=2). LC-MS/MS demonstrated the presence of lambda, but
      not kappa, light chain as well as serum amyloid P in all amyloidomas. lambda
      Light-chain immunostaining was noted in amyloid (n=5), although demonstrable
      monotypic lymphoplasmacytic cells were seen in only one case. Conversely, in
      PDNOS kappa, but not lambda, was evident in five cases, both light chains being
      present in a single case. In three cases of PDNOS, a low-grade B-cell lymphoma
      consistent with marginal zone lymphoma was present in the brain specimen (n=2) or
      spleen (n=1). Lastly, in the 'intracellular crystals' group, the crystals were
      present within CD68+ macrophages in one case wherein kappa-light chain was found
      by LC-MS/MS only; the pathology was consistent with crystal-storing
      histiocytosis. In the second case, the crystals contained immunoglobulin G within
      CD138+ plasma cells. Our results show that proteinaceous deposits in the nervous
      system contain immunoglobulin components and LC-MS/MS accurately identifies the
      content of these deposits in clinical biopsy specimens. LC-MS/MS represents a
      novel application for characterization of these deposits and is of diagnostic
      utility in addition to standard immunohistochemical analyses.

PMID- 18711354
TI  - Smad3 knockout mice exhibit impaired intestinal mucosal healing.
AB  - Altered transforming growth factor-beta (TGFbeta) expression may contribute to
      inflammatory bowel disease and modulate epithelial cell restitution. Interference
      with TGFbeta-mediated signaling inhibits excisional skin wound healing, but
      accelerates healing of incisional cutaneous wounds and wounds in some other
      tissues. Therefore, we sought to clarify the potential role of Smad3-dependent
      TGFbeta signaling in intestinal mucosal healing in Smad3 null mice. Jejunal
      serosal application of filter disks saturated with 75% acetic acid yielded a
      circumscribed reproducible ischemic mucosal ulcer 1 day later. We compared ulcer
      area at 3 and 5 days to day 1 in Smad3 knockout mice and syngeneic wild-type
      mice, and evaluated mucosal immunoreactivity at the ulcer edge for TGFbeta,
      phosphorylated (activated) focal adhesion kinase (pFAK), phosphorylated
      extracellular signal-related kinase (pERK), proliferating cell nuclear antigen
      and apoptosis by TUNEL. Ulcer healing in Smad3 null mice was 17% less at day 3
      (n=14, P=0.022) and 15% less at day 5 (n=14, P=0.004) than in wild-type
      littermates. In wild-type mice, pFAK, pERK and TGFbeta immunoreactivity were
      elevated in epithelium immediately adjacent to the ulcer compared with more
      distant mucosa. However, this pattern of immunoreactivity for pFAK, pERK and
      TGFbeta was not observed in Smad3 null mice. Smad3 null mice exhibited increased
      epithelial proliferation and no differences in apoptotic cell death compared with
      wild types, suggesting that ulcer healing may reflect differences in restitutive
      cell migration. Thus, Smad3-dependent disruption of the TGFbeta signaling pathway
      impairs the healing of murine intestinal mucosal ulcers and alters patterns of
      activated FAK and ERK immunoreactivity important for cell migration at the ulcer
      edge. These studies suggest a significant role for Smad3-dependent TGFbeta
      signaling in intestinal mucosal healing.

PMID- 18711356
TI  - A tumour suppressor function of caspase-8?

PMID- 18711365
TI  - Collaborative genome-wide association analysis supports a role for ANK3 and
      CACNA1C in bipolar disorder.
AB  - To identify susceptibility loci for bipolar disorder, we tested 1.8 million
      variants in 4,387 cases and 6,209 controls and identified a region of strong
      association (rs10994336, P = 9.1 x 10(-9)) in ANK3 (ankyrin G). We also found
      further support for the previously reported CACNA1C (alpha 1C subunit of the L
      type voltage-gated calcium channel; combined P = 7.0 x 10(-8), rs1006737). Our
      results suggest that ion channelopathies may be involved in the pathogenesis of
      bipolar disorder.

PMID- 18711366
TI  - SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian
      and European populations.
AB  - We conducted a genome-wide association study using 207,097 SNP markers in
      Japanese individuals with type 2 diabetes and unrelated controls, and identified
      KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) to be a
      strong candidate for conferring susceptibility to type 2 diabetes. We detected
      consistent association of a SNP in KCNQ1 (rs2283228) with the disease in several
      independent case-control studies (additive model P = 3.1 x 10(-12); OR = 1.26,
      95% CI = 1.18-1.34). Several other SNPs in the same linkage disequilibrium (LD)
      block were strongly associated with type 2 diabetes (additive model: rs2237895, P
      = 7.3 x 10(-9); OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 x 10(-13); OR =
      1.41, 95% CI = 1.29-1.55). The association of these SNPs with type 2 diabetes was
      replicated in samples from Singaporean (additive model: rs2237895, P = 8.5 x 10(
      3); OR = 1.14, rs2237897, P = 2.4 x 10(-4); OR = 1.22) and Danish populations
      (additive model: rs2237895, P = 3.7 x 10(-11); OR = 1.24, rs2237897, P = 1.2 x
      10(-4); OR = 1.36).

PMID- 18711367
TI  - Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus.
AB  - We carried out a multistage genome-wide association study of type 2 diabetes
      mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls
      and 100,000 SNPs. The most significant association was obtained with SNPs in
      KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15
      showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association
      of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese
      and European ancestry as well as in two independent Japanese populations, and
      meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361
      controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for
      rs2237892. Among control subjects, the risk allele of this polymorphism was
      associated with impairment of insulin secretion according to the homeostasis
      model assessment of beta-cell function or the corrected insulin response. Our
      data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of
      different ancestries.

PMID- 18711369
TI  - Report from Durham.

PMID- 18711368
TI  - tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia.
AB  - Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative
      autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the
      cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical
      atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4,
      we identified mutations in three of the four different subunits of the tRNA
      splicing endonuclease complex. Our findings point to RNA processing as a new
      basic cellular impairment in neurological disorders.

PMID- 18711372
TI  - The bottom line.

PMID- 18711373
TI  - Chemical biology at the US National Science Foundation.

PMID- 18711374
TI  - Chemical biology in China takes on signal transduction.

PMID- 18711375
TI  - Foundation funding and chemical biology.

PMID- 18711376
TI  - ERA-Chemistry.

PMID- 18711377
TI  - From yeast to alkaloids.

PMID- 18711378
TI  - Unexpected N-terminal editing: a cysteine protease that cuts and pastes.

PMID- 18711379
TI  - Cross-dressing proteins by olefin metathesis.

PMID- 18711380
TI  - 20S ways to apoptosis.

PMID- 18711381
TI  - Chloroplast SRP takes another road.

PMID- 18711383
TI  - Strong magneto-chiral dichroism in enantiopure chiral ferromagnets.
AB  - As materials science is moving towards the synthesis, the study and the
      processing of new materials exhibiting well-defined and complex functions, the
      synthesis of new multifunctional materials is one of the important challenges.
      One of these complex physical properties is magneto-chiral dichroism which
      arises, at second order, from the coexistence of spatial asymmetry and
      magnetization in a material. Herein we report the first measurement of strong
      magneto-chiral dichroism in an enantiopure chiral ferromagnet. The ab initio
      synthesis of the enantiopure chiral ferromagnet is based on an enantioselective
      self-assembly, where a resolved chiral quaternary ammonium cation imposes the
      absolute configurations of the metal centres within chromium-manganese two
      dimensional oxalate layers. The ferromagnetic interaction between Cr(III) and
      Mn(II) ions leads to a Curie temperature of 7 K. The magneto-chiral dichroic
      effect is enhanced by a factor of 17 when entering into the ferromagnetic phase.

PMID- 18711384
TI  - Boosting migration of large particles by solute contrasts.
AB  - Brownian diffusion is a keystone concept in a large variety of domains, from
      physics, chemistry to biology. Diffusive transport controls situations as diverse
      as reaction-diffusion processes in biology and chemistry, Brownian ratchet
      processes, dispersion in microfluidic devices or even double-diffusive
      instability and salt-fingering phenomena in the context of ocean mixing. Although
      these examples span a broad range of length scales, diffusive transport becomes
      increasingly inefficient for larger particles. Applications, for example, in
      microfluidics, usually have recourse to alternative driving methods involving
      external sources to induce and control migration. Here, we demonstrate
      experimentally a strongly enhanced migration of large particles, achieved by
      slaving their dynamics to that of a fast carrier species, a dilute salt. The
      underlying fast salt diffusion leads to an apparent diffusive-like dynamics of
      the large particles, which is up to two orders of magnitude faster than their
      natural 'bare' diffusion. Moreover both spreading and focusing of the particle
      assembly can be achieved on demand. A model description shows a remarkable
      quantitative agreement with all measured data. Applications of this process are
      illustrated in microfluidics for filtering and concentrating operations, as well
      as in conjunction with standard hydrodynamic focusing. In a wider perspective,
      this mechanism can affect a broad range of scales and phenomena, from biological
      transport to the dispersion of sediments and pollutants in oceanographic
      situations.

PMID- 18711385
TI  - Multi-quantum-well nanowire heterostructures for wavelength-controlled lasers.
AB  - Rational design and synthesis of nanowires with increasingly complex structures
      can yield enhanced and/or novel electronic and photonic functions. For example,
      Ge/Si core/shell nanowires have exhibited substantially higher performance as
      field-effect transistors and low-temperature quantum devices compared with
      homogeneous materials, and nano-roughened Si nanowires were recently shown to
      have an unusually high thermoelectric figure of merit. Here, we report the first
      multi-quantum-well (MQW) core/shell nanowire heterostructures based on well
      defined III-nitride materials that enable lasing over a broad range of
      wavelengths at room temperature. Transmission electron microscopy studies show
      that the triangular GaN nanowire cores enable epitaxial and dislocation-free
      growth of highly uniform (InGaN/GaN)n quantum wells with n=3, 13 and 26 and InGaN
      well thicknesses of 1-3 nm. Optical excitation of individual MQW nanowire
      structures yielded lasing with InGaN quantum-well composition-dependent emission
      from 365 to 494 nm, and threshold dependent on quantum well number, n. Our work
      demonstrates a new level of complexity in nanowire structures, which potentially
      can yield free-standing injection nanolasers.

PMID- 18711386
TI  - Spin Rabi flopping in the photocurrent of a polymer light-emitting diode.
AB  - Electron spin is fundamental in electrical and optical properties of organic
      electronic devices. Despite recent interest in spin mixing and spin transport in
      organic semiconductors, the actual spin coherence times in these materials have
      remained elusive. Measurements of spin coherence provide impartial insight into
      spin relaxation mechanisms, which is significant in view of recent models of spin
      dependent transport and recombination involving high levels of spin mixing. We
      demonstrate coherent manipulation of spins in an organic light-emitting diode
      (OLED), using nanosecond pulsed electrically detected electron spin resonance to
      drive singlet-triplet spin Rabi oscillations. By measuring the change in
      photovoltaic response due to spin-dependent recombination, we demonstrate spin
      control of electronic transport and thus directly observe spin coherence over 0.5
      s. This surprisingly slow spin dephasing underlines that spin mixing is not
      responsible for magnetoresistance in OLEDs. The long coherence times and the spin
      manipulation demonstrated are crucially important for expanding the impact of
      organic spintronics.

PMID- 18711389
TI  - Success in sight: The eyes have it! Ocular gene therapy trials for LCA look
      promising.

PMID- 18711388
TI  - Industry funding and the reporting quality of large long-term weight loss trials.
AB  - BACKGROUND: Quality of reporting (QR) in industry-funded research is a concern of
      the scientific community. Greater scrutiny of industry-sponsored research
      reporting has been suggested, although differences in QR by sponsorship type have
      not been evaluated in weight loss interventions. OBJECTIVE: To evaluate the
      association of funding source and QR of long-term obesity randomized clinical
      trials (RCT). METHODS: We analysed papers that reported long-term weight loss
      trials. Articles were obtained through searches of Medline, HealthStar, and the
      Cochrane Controlled Trials Register between the years 1966 and 2003. QR scores
      were determined for each study based upon expanded criteria from the Consolidated
      Standards for Reporting Trials (CONSORT) checklist for a maximum score of 44
      points. Studies were coded by category of industry support (0=no industry
      support, 1=industry support, 2=in kind contribution from industry and 3=duality
      of interest reported). Individual CONSORT reporting criteria were tabulated by
      funding type. An independent samples t-test compared the differences in QR scores
      by funding source and the Wilcox-Mann-Whitney test and generalised estimating
      equations (GEE) were used for sensitivity analyses. RESULTS: Of the 63 RCTs
      evaluated, 67% were industry-supported trials. Industry funding was associated
      with higher QR score in long-term weight loss trials compared with nonindustry
      funded studies (mean QR (s.d.): industry=27.9 (4.1), nonindustry=23.4 (4.1);
      P<0.0005). The Wilcox-Mann-Whitney test confirmed this result (P<0.0005).
      Controlling for the year of publication and whether the paper was published
      before the CONSORT statement was released in the GEE regression analysis, the
      direction and magnitude of effect were similar and statistically significant
      (P=0.035). Of the individual criteria that prior research has associated with
      biases, industry funding was associated with greater reporting of intent-to-treat
      analysis (P=0.0158), but was not different from nonindustry studies in reporting
      of treatment allocation and blinding. CONCLUSION: Our findings suggest that the
      efforts to improve reporting quality be directed to all obesity RCTs,
      irrespective of funding source.

PMID- 18711393
TI  - Divergence of fMRI and neural signals in V1 during perceptual suppression in the
      awake monkey.
AB  - The role of primary visual cortex (V1) in determining the contents of perception
      is controversial. Human functional magnetic resonance imaging (fMRI) studies of
      perceptual suppression have revealed a robust drop in V1 activity when a stimulus
      is subjectively invisible. In contrast, monkey single-unit recordings have failed
      to demonstrate such perception-locked changes in V1. To investigate the basis of
      this discrepancy, we measured both the blood oxygen level-dependent (BOLD)
      response and several electrophysiological signals in two behaving monkeys. We
      found that all signals were in good agreement during conventional stimulus
      presentation, showing strong visual modulation to presentation and removal of a
      stimulus. During perceptual suppression, however, only the BOLD response and the
      low-frequency local field potential (LFP) power showed decreases, whereas the
      spiking and high-frequency LFP power were unaffected. These results demonstrate
      that the coupling between the BOLD and electrophysiological signals in V1 is
      context dependent, with a marked dissociation occurring during perceptual
      suppression.

PMID- 18711399
TI  - Simulating T-cell motility in the lymph node paracortex with a packed lattice
      geometry.
AB  - Agent-based simulation modelling of T-cell trafficking, activation and
      proliferation in the lymph node paracortex requires a model for cell motility.
      Such a model must be able to reproduce the observed random-walk behaviour of T
      cells, while accommodating large numbers of tightly packed cells, and must be
      computationally efficient. We report the development of a motility model, based
      on a three-dimensional lattice geometry, that meets these objectives. Cells make
      discrete jumps between neighbouring lattice sites in directions that are randomly
      determined from specified discrete probability distributions, which are defined
      by a small number of parameters. It is shown that the main characteristics of the
      random motion of T cells as typically observed in vivo can be reproduced by
      suitable specification of model parameters. The model is computationally highly
      efficient and provides a suitable engine for a model capable of simulating the
      full T-cell population of the paracortex.

PMID- 18711400
TI  - Human beta-defensin 3 binds to hemagglutinin B (rHagB), a non-fimbrial adhesin
      from Porphyromonas gingivalis, and attenuates a pro-inflammatory cytokine
      response.
AB  - Regulatory mechanisms in mucosal secretions and tissues recognize antigens and
      attenuate pro-inflammatory cytokine responses. Here, we asked whether human beta
      defensin 3 (HBD3) serves as an upstream suppressor of cytokine signaling that
      binds and attenuates pro-inflammatory cytokine responses to recombinant
      hemagglutinin B (rHagB), a non-fimbrial adhesin from Porphyromonas gingivalis
      strain 381. We found that HBD3 binds to immobilized rHagB and produces a
      significantly higher resonance unit signal in surface plasmon resonance
      spectroscopic analysis, than HBD2 and HBD1 that are used as control defensins.
      Furthermore, we found that HBD3 significantly attenuates (P<0.05) the interleukin
      (IL)-6, IL-10, granulocyte macrophage colony stimulating factor (GM-CSF) and
      tumor-necrosis factor-alpha (TNF-alpha) responses induced by rHagB in human
      myeloid dendritic cell culture supernatants and the extracellular signal
      regulated kinases (ERK 1/2) response in human myeloid dendritic cell lysates.
      Thus, HBD3 binds rHagB and this interaction may be an important initial step to
      attenuate a pro-inflammatory cytokine response and an ERK 1/2 response.

PMID- 18711401
TI  - Glioblastoma-secreted factors induce IGFBP7 and angiogenesis by modulating Smad-2
      dependent TGF-beta signaling.
AB  - Insulin-like growth factor-binding protein 7 (IGFBP7) is a selective biomarker of
      glioblastoma (GBM) vessels, strongly expressed in tumor endothelial cells and
      vascular basement membrane. IGFBP7 gene regulation and its potential role in
      tumor angiogenesis remain unclear. Mechanisms of IGFBP7 induction and its
      angiogenic capacity were examined in human brain endothelial cells (HBECs)
      exposed to tumor-like conditions. HBEC treated with GBM cell (U87MG)-conditioned
      media (-CM) exhibited fourfold upregulation of IGFBP7 mRNA and protein compared
      to control cells. IGFBP7 gene regulation in HBEC was methylation independent.
      U87MG-CM analysed by enzyme-linked immunosorbent assay contained approximately 5
      pM transforming growth factor (TGF)-beta1, a concentration sufficient to
      stimulate IGFBP7 in HBEC to similar levels as U87MG-CM. Both pan-TGF-beta
      neutralizing antibody (1D11) and the TGF-beta1 receptor (activin receptor-like
      kinase 5, ALK5) antagonist, SB431542, blocked U87MG-CM-induced IGFBP7 expression
      in HBEC, indicating that TGF-beta1 is an important tumor-secreted effector
      capable of IGFBP7 induction in endothelial cells. HBEC exposed to either U87MG-CM
      or IGFBP7 protein exhibited increased capillary-like tube (CLT) formation in
      Matrigel. Both TGF-beta1- and U87MG-CM-induced Smad-2 phosphorylation and U87MG
      CM-induced CLT formation in HBEC were inhibited by the ALK5 antagonist, SB431542.
      These data suggest that proangiogenic IGFBP7 may be induced in brain endothelial
      cells by TGF-betas secreted by GBM, most likely through TGF-beta1/ALK5/Smad-2
      pathway.

PMID- 18711387
TI  - First versus repeat treatment with a lifestyle intervention program: attendance
      and weight loss outcomes.
AB  - OBJECTIVE: Following unblinding of the Diabetes Prevention Program (DPP) results,
      a 16-session lifestyle intervention program was offered to all study
      participants, including those who had initially been randomized to lifestyle
      treatment. This study compares the effects of the lifestyle program between
      participants who had previous exposure and those who had not. DESIGN: A 16
      session behavioral intervention was conducted in groups at each of the 27 DPP
      sites during a transitional (bridge) period from the DPP trial to the DPP
      Outcomes Study (DPPOS). Session participation for this 6-month behavioral weight
      loss program was confirmed by originally randomized treatment groups. SUBJECTS
      AND MEASUREMENTS: Independently assessed weight measurements were available
      within a 7-month period before and after the program for 2808 ethnically diverse
      participants. RESULTS: Participants from the lifestyle group in the DPP were the
      least likely to attend a repeat offering of a 16-session behavioral weight loss
      program conducted in groups. Weight loss during the transitional lifestyle
      program was strongly related to the duration of attendance in the three groups
      that were participating in the program for the first time (metformin, placebo and
      troglitazone), but not related to amount of earlier weight loss. CONCLUSION:
      Individuals who were naive to the behavioral program lost a greater amount of
      weight and this was strongly related to their degree of participation. A second
      exposure to a behavioral weight loss program resulted in unsatisfactory low
      attendance rates and weight loss.

PMID- 18711402
TI  - Full-length hdmX transcripts decrease following genotoxic stress.
AB  - Previous studies have suggested that the mdmX gene is constitutively transcribed,
      and that MdmX protein activity is instead controlled by cellular localization and
      DNA damage induced Mdm2-mediated ubiquitination leading to proteasomal
      degradation. In these studies, we report that the human mdmX (hdmX) mRNA is
      reproducibly decreased in various human cell lines following treatment with
      various DNA-damaging agents. Repression of hdmX transcripts is observed in DNA
      damaged HCT116 colon cancer cells and in isogenic p53(-/-) cells, suggesting that
      this effect is p53-independent. Reduction in the amount of hdmX transcript occurs
      in both human tumor cell lines and primary human diploid fibroblasts, and results
      in a significant reduction of HdmX protein. Examination of hdmX promoter activity
      suggests that damage-induced repression of hdmX mRNA is not significantly
      impacted by transcription initiation. In contrast, changes in hdmX mRNA splicing
      appear to partly explain the reduction in full-length hdmX mRNA levels in tumor
      cell lines with the destabilization of full-length hdmX transcripts, potentially
      through microRNA miR-34a regulation, also impacting transcript levels. Taken
      together, this study uncovers previously unrecognized cellular mechanisms by
      which hdmX mRNA levels are kept low following genotoxic stress.

PMID- 18711405
TI  - Randomized, controlled trial of intramuscular or intracoronary injection of
      autologous bone marrow cells into scarred myocardium during CABG versus CABG
      alone.
AB  - BACKGROUND: Studies of the transplantation of autologous bone marrow cells (BMCs)
      in patients with chronic ischemic heart disease have assessed effects on viable,
      peri-infarct tissue. We conducted a single-blinded, randomized, controlled study
      to investigate whether intramuscular or intracoronary administration of BMCs into
      nonviable scarred myocardium during CABG improves contractile function of scar
      segments compared with CABG alone. METHODS: Elective CABG patients (n = 63), with
      established myocardial scars diagnosed as akinetic or dyskinetic segments by
      dobutamine stress echocardiography and confirmed at surgery, were randomly
      assigned CABG alone (control) or CABG with intramuscular or intracoronary
      administration of BMCs. The BMCs, which were obtained at the time of surgery,
      were injected into the mid-depth of the scar in the intramuscular group or via
      the graft conduit supplying the scar in the intracoronary group. Contractile
      function was assessed in scar segments by dobutamine stress echocardiography
      before and 6 months after treatment. RESULTS: The proportion of patients showing
      improved wall motion in at least one scar segment after BMC treatment was not
      different to that observed in the control group (P = 0.092). Quantitatively,
      systolic fractional thickening in scar segments did not improve with BMC
      administration. Furthermore, BMCs did not improve scar transmurality, infarct
      volume, left ventricular volume, or ejection fraction. CONCLUSION: Injection of
      autologous BMCs directly into the scar or into the artery supplying the scar is
      safe but does not improve contractility of nonviable scarred myocardium, reduce
      scar size, or improve left ventricular function more than CABG alone.

PMID- 18711406
TI  - Management of recurrent and refractory Cushing disease.
AB  - Cushing disease is most frequently caused by pituitary adenomas that secrete
      adrenocorticotrophic hormone. Transsphenoidal surgery is the treatment of choice
      in patients with these tumors because of reported remission rates of 69-93%. More
      challenging for neurosurgeons and endocrinologists, however, is management of the
      remaining patients whose Cushing disease is refractory to initial transsphenoidal
      surgery or recurs after initial remission. Here, we review the treatment options
      and latest surgical, medical, and radiosurgical advances for patients who have
      persistent or recurrent Cushing disease after transsphenoidal surgery.

PMID- 18711403
TI  - Critical pathways in cellular senescence and immortalization revealed by gene
      expression profiling.
AB  - Bypassing cellular senescence and becoming immortal is a prerequisite step in the
      tumorigenic transformation of a cell. It has long been known that loss of a key
      tumor suppressor gene, such as p53, is necessary, but not sufficient, for
      spontaneous cellular immortalization. Therefore, there must be additional
      mutations and/or epigenetic alterations required for immortalization to occur.
      Early work on these processes included somatic cell genetic studies to estimate
      the number of senescence genes, and microcell-mediated transfer of chromosomes
      into immortalized cells to identify putative senescence-inducing genetic loci.
      These principal studies laid the foundation for the field of
      senescence/immortalization, but were labor intensive and the results were
      somewhat limited. The advent of gene expression profiling and bioinformatics
      analysis greatly facilitated the identification of genes and pathways that
      regulate cellular senescence/immortalization. In this review, we present the
      findings of several gene expression profiling studies and supporting functional
      data, where available. We identified universal genes regulating
      senescence/immortalization and found that the key regulator genes represented six
      pathways: the cell cycle pRB/p53, cytoskeletal, interferon-related, insulin
      growth factor-related, MAP kinase and oxidative stress pathway. The
      identification of the genes and pathways regulating senescence/immortalization
      could provide novel molecular targets for the treatment and/or prevention of
      cancer.

PMID- 18711407
TI  - Do NALP5 antibodies correlate with hypoparathyroidism in patients with APS-1?

PMID- 18711404
TI  - The use of high-sensitivity assays for C-reactive protein in clinical practice.
AB  - High-sensitivity assays that accurately measure levels of the inflammatory
      biomarker C-reactive protein have been proposed for use in assessments of risk
      for cardiovascular disease (CVD). A growing body of evidence supports
      recommendations for these tests in selected asymptomatic individuals deemed to be
      at intermediate risk of CVD according to traditional risk-factor assessments and
      who do not already warrant chronic treatment with aspirin and statin therapy.
      Data suggests that these high-sensitivity assays should be used in combination
      with measurements of LDL-cholesterol levels to assist risk stratification of
      selected patients for prevention of CVD.

PMID- 18711408
TI  - How effective is risedronate in preventing bone loss in patients on high-dose
      steroids?

PMID- 18711410
TI  - Should vardenafil be used for the treatment of lower urinary tract symptoms
      associated with BPH?

PMID- 18711409
TI  - HIV and prostate cancer: a systematic review of the literature.
AB  - Malignancy occurs with increased frequency in the HIV-positive population. The
      true incidence of prostate cancer in this population is unknown. In the few cases
      that have been presented in the literature, prostate cancer in HIV-positive men
      appears to behave much like it does in HIV-negative men. Prostate cancer is the
      most common malignancy in men and the second leading cause of cancer death.
      Approximately 800,000 men in the United States are HIV positive, and innovative
      therapies have dramatically improved survival. HIV disproportionately impacts
      ethnic groups with increased risk of prostate cancer and has been associated with
      increases in the incidence of certain malignancies. Despite the high prevalence
      of both diseases, there is relatively little literature about prostate cancer in
      HIV-positive patients. There is no consensus on how to screen or treat this
      patient population. We review the literature with regards to incidence,
      screening, treatment, and outcomes of this poorly characterized population. We
      briefly discuss the impact of highly active antiretroviral therapy and
      testosterone supplementation in the development of prostate cancer. A systematic
      review of the literature was conducted using MEDLINE key words 'HIV,' 'prostate,'
      'prostate cancer' and 'AIDS.' Manual bibliographic review of cross-referenced
      items was also performed. A total of 176 unique abstracts and publications were
      reviewed; many authors provided data on the incidence of HIV and various
      malignancies including prostate cancer. Twelve unique publications providing
      detailed information on 60 patients with HIV and prostate cancer were identified.
      Prostate cancer is a common malignancy in HIV-positive men. With improved
      therapies for HIV and increasing survival, the importance for screening and
      treating prostate cancer is increasing. Acute outcomes of treatment do not
      demonstrate increased acute morbidity; however long-term outcomes have not been
      reported.

PMID- 18711411
TI  - Gross hematuria from an ileal conduit as a first presentation of portal
      hypertension.
AB  - BACKGROUND: A 76-year-old man who underwent cystoprostatectomy with ileal conduit
      urinary diversion for muscle-invasive bladder cancer presented to his urologist 4
      years later with episodes of spontaneous gross hematuria filling his ostomy bag
      with fresh clots. INVESTIGATIONS: Physical examination, urine culture, urine
      cytology, peripheral smear, complete blood count, loopogram, CT-intravenous
      pyelogram, loop endoscopy, bilateral ureteroscopy, liver function tests, CT
      angiography, (99m)Tc-tagged red cell scan, hepatitis panel, measurement of
      transjugular wedge pressure, transjugular liver biopsy with pathologic analysis
      and re-evaluation of CT angiogram. DIAGNOSIS: Hematuria secondary to portal
      hypertension. MANAGEMENT: The patient initially underwent revision of the
      ureteroileal anastomosis on the basis of the results of the (99m)Tc-tagged red
      cell scan, but hematuria recurred 9 months later. Once the hepatology service
      identified portal hypertension, the patient was taken to the operating room for
      ligation of a large venous communication between the ileal conduit and a branch
      of the inferior epigastric vein. He recovered well and was asymptomatic for 8
      months. He was followed up by the hepatology service for his newly diagnosed
      portal hypertension secondary to cirrhosis.

PMID- 18711412
TI  - Endoscopic clipping for the management of gastrointestinal bleeding.
AB  - Endoscopic clipping is a safe and effective technique for the treatment of
      various bleeding gastrointestinal lesions. Randomized controlled trials and a
      meta-analysis have shown comparable efficacy between clipping and conventional
      contact thermal therapy for definitive hemostasis of nonvariceal upper
      gastrointestinal hemorrhage. Clipping also seems to be efficacious for selected
      lower gastrointestinal bleeding lesions, such as diverticular bleeding and
      postpolypectomy bleeding. Proficiency in clip application and endoscopic
      identification of lesions that are amenable to clipping are key determinants of a
      successful outcome.

PMID- 18711413
TI  - Quality improvement in gastroenterology: a US perspective.

PMID- 18711414
TI  - Empiric PPI therapy or endoscopy for the initial management of patients with GERD
      in the absence of alarm features?

PMID- 18711415
TI  - What is the long-term efficacy of laparoscopic Nissen fundoplication?

PMID- 18711416
TI  - Is rosiglitazone a promising treatment for ulcerative colitis?
AB  - In this Practice Point commentary, we discuss the findings and limitations of a
      randomized, placebo-controlled trial conducted by Lewis and colleagues that
      examined the efficacy of rosiglitazone for the treatment of patients with mild-to
      moderately active ulcerative colitis. The results show that rosiglitazone had
      superior efficacy to placebo for inducing clinical response and remission.
      However, the efficacy of rosiglitazone in this setting was modest. We believe
      that this finding might be attributable to the high numbers of patients included
      in the trial who were refractory to conventional therapy. Rosiglitazone might be
      more effective if combined with 5-aminosalicylic acid therapy and used in
      patients with less-refractory disease. We highlight the issues to consider when
      interpreting and generalizing these findings to clinical practice.

PMID- 18711417
TI  - Physiatrists' opinions and practice patterns for bone health after SCI.
AB  - STUDY DESIGN: Self-report survey. OBJECTIVE: To ascertain physiatrists' opinions
      and current practice patterns for bone health management after spinal cord injury
      (SCI). PARTICIPANTS: Physiatrists who work in teaching rehabilitation centers in
      Canada. METHODS: A 4-page 17-question survey (available in French and English)
      was sent to working physiatrists in all major Canadian SCI rehabilitation
      centers. RESULTS: We had an 85% response rate (22 responses). Physiatrists
      reported that they should be managing bone health issues after SCI in conjunction
      with family physicians, and most respondents assess and treat for bone health
      after SCI. However, just over one-third of the physiatrists reported that the
      current treatment options are not effective for low bone mass; there was more
      support for pharmacological treatments than there was for rehabilitation
      modalities. CONCLUSION: Bone health after SCI is an important health concern that
      is being managed by physiatrists; however, more discussion and research is needed
      to ascertain the effectiveness of assessment and treatment options for low bone
      mass.

PMID- 18711418
TI  - Isolated longitudinal myelitis: a report of six cases.
AB  - STUDY DESIGN: Retrospective chart review.ObjectiveTo report six patients with
      isolated longitudinal myelitis (LM). SETTING: Outpatients at Multiple Sclerosis
      Center/Clinic Vanderbilt University Medical Center. METHODS: 1. PATIENTS:
      PATIENTS treated for LM in whom evidence for multiple sclerosis (MS),
      neuromyelitis optica (NMO) and systemic inflammatory disorders such as systemic
      lupus erythematosus (SLE) was lacking. 2. INTERVENTIONS: Clinical, laboratory and
      imaging data, treatment and outcomes were reviewed. 3. MAIN OUTCOME MEASURES: LM
      in the absence of optic neuritis, normal or nonspecific brain magnetic resonance
      imaging (MRI) findings, the absence of NMO antibody. RESULTS: All presented with
      monophasic myelitis with variable loss of motor, sensory and bowel/bladder
      functions. MRIs of the brain were normal (five cases), and in the sixth showed a
      single T2 hyperintense lesion, which was interpreted as an ischemic lesion due to
      small-vessel disease. MRIs of the spinal cord of all patients showed swelling and
      T2 hyperintense lesions with patchy contrast enhancement that extended from the
      cervicomedullary junction to the conus medullaris. Two of these patients received
      rituximab with clinical benefit. Another patient received one dose of rituximab,
      developed an allergic reaction, received further treatments with azathioprine and
      also made a good recovery. In one patient, approval for rituximab was obtained
      several months after the inflammation had subsided, and she has shown only a
      minimal improvement. The two patients who did not receive rituximab made no
      significant recovery from their maximal neurological deficits. CONCLUSIONS:
      Isolated LM may be a new clinical syndrome, or a variant of NMO.

PMID- 18711419
TI  - MRI-detected bone marrow edema in early rheumatoid arthritis.

PMID- 18711420
TI  - Progressive arm and leg stiffness in a patient with chronic renal impairment.
AB  - BACKGROUND: A 60-year-old white woman with a history of breast cancer, autoimmune
      hemolytic anemia, type 2 diabetes mellitus, peripheral vascular disease, and
      chronic renal insufficiency presented with stiffness in her arms and legs of 3
      months' duration. She had undergone multiple MRI and magnetic resonance
      angiography examinations with gadolinium-containing contrast media over the last
      2 years. INVESTIGATIONS: Complete physical examination including thorough skin
      examination; laboratory examinations including CBC, urinalysis, serum creatinine,
      protein electrophoresis and C-reactive protein; antinuclear antibody assay;
      Westergren erythrocyte sedimentation rate; and an excisional skin biopsy.
      DIAGNOSIS: Nephrogenic systemic fibrosis (also known as nephrogenic fibrosing
      dermopathy). MANAGEMENT: Symptomatic treatment, physical therapy, and a brief
      trial of imatinib mesylate.

PMID- 18711421
TI  - ANCA-negative glomerulonephritis associated with nonasthmatic Churg-Strauss
      syndrome.
AB  - BACKGROUND: A 36-year-old white male with a history of allergic rhinitis and
      sinusitis presented to the emergency room with abdominal pain and diarrhea.
      Physical examination revealed fever, hypoxemia and a maculopapular rash.
      Laboratory tests showed proteinuria, hematuria, leukocytosis, eosinophilia and an
      elevated erythrocyte sedimentation rate. INVESTIGATIONS: Physical examination,
      urine and blood analysis and culture, chest radiography, chest and abdominal CT,
      esophagogastroduodenoscopy, skin and kidney biopsy, serology and renal
      ultrasound. DIAGNOSIS: Pauci-immune focal necrotizing glomerulonephritis with
      crescents and interstitial eosinophilia, consistent with Churg-Strauss syndrome.
      MANAGEMENT: The patient was treated with methylprednisolone 1 g/day intravenously
      for 3 days. He also received oral clotrimazole and combined oral sulfamethoxazole
      and trimethoprim for prophylaxis against candidiasis and pneumonia, respectively.
      He left the hospital against medical advice and was lost to follow-up.

PMID- 18711422
TI  - Comparing the efficacy of intravenous iron and oral iron in nondialysis patients
      with chronic kidney disease.
AB  - This Practice Point commentary discusses the findings and limitations of a phase
      III trial by Spinowitz et al. that compared oral and intravenous iron therapies
      in nondialysis patients with chronic kidney disease. In total, 304 patients were
      randomly assigned in a 3:1 ratio to receive either two 510 mg doses of
      intravenous ferumoxytol within 5+/-3 days or 200mg of elemental oral iron daily
      for 21 days. At day 35, hemoglobin levels had increased significantly more in
      patients who had received intravenous ferumoxytol than in those who had received
      oral iron therapy. Ferumoxytol was well tolerated. The superiority of ferumoxytol
      over other intravenous iron preparations, however, needs to be investigated, and
      optimal serum ferritin levels for the nondialysis CKD population need to be
      defined.

PMID- 18711425
TI  - A weak balance: the contribution of muscle weakness to postural instability and
      falls.
AB  - Muscle strength is a potentially important factor contributing to postural
      control. In this article, we consider the influence of muscle weakness on
      postural instability and falling. We searched the literature for research
      evaluating muscle weakness as a risk factor for falls in community-dwelling
      elderly individuals, for evidence that strength training reduces falls, and for
      pathophysiological evidence from patients with neuromuscular disease that
      supports the link between muscle weakness and falls. In virtually all studies
      that included strength testing, muscle weakness was a consistent risk factor for
      falls in the elderly. Studies that evaluated the merits of muscle strength
      training often showed a reduction in fall rates, particularly when strength
      training was a component of a multifactorial intervention, although it was
      unclear whether strength training alone led to a fall reduction. Surprisingly few
      studies addressed the pathophysiological relationship between muscle strength and
      balance control. We conclude that muscle weakness is an important risk factor for
      falls that is potentially amenable to therapeutic intervention, and that future
      studies should further clarify the role of muscle weakness in balance control and
      the pathophysiology of falls.

PMID- 18711426
TI  - Combined transarterial chemoembolization and radiofrequency ablation for
      hepatocellular carcinoma.
AB  - Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are both
      efficacious in treating well-selected patients who have hepatocellular carcinoma
      (HCC). The sequential combination of these two modalities has a sound theoretical
      basis and raises the probability of complete local response in tumors that are
      beyond the size at which the likelihood of failure with RFA alone begins to rise.
      Cheng et al. have found that when limited to patients with well-compensated liver
      disease, combined TACE and RFA does not seem to dramatically increase the risk of
      complications beyond the risk levels associated with the individual procedures.
      The survival benefit demonstrated in this recent article is, however, an artifact
      of a rigid study design that did not allow rational selection of treatment on the
      basis of individual patient and tumor characteristics. This study bolsters the
      evidence that the combination of TACE with RFA enhances local response,
      strengthening the status of nonsurgical treatment compared with resection for the
      treatment of early HCC.

PMID- 18711427
TI  - Response criteria for glioma.
AB  - The current method for assessing the response to therapy of glial tumors was
      described by Macdonald et al. in 1990. Under this paradigm, response
      categorization is determined on the basis of changes in the cross-sectional area
      of a tumor on neuroimaging, coupled with clinical assessment of neurological
      status and corticosteroid utilization. These categories of response have certain
      limitations; for example, cross-sectional assessment is not as accurate as
      volumetric assessment, which is now feasible. Disentangling antitumor effects of
      therapies from their effects on blood-brain barrier permeability can be
      challenging. The use of insufficient response criteria might be overestimating
      the true benefits of drugs in early-stage studies, and, therefore, such therapies
      could mistakenly move forward into later phases, only to result in disappointment
      when overall survival is measured. We propose that studies report both
      radiographic and clinical response rates, use volumetric rather than cross
      sectional area to measure lesion size, and incorporate findings from mechanistic
      imaging and blood biomarker studies more frequently, and also suggest that
      investigators recognize the limitations of imaging biomarkers as surrogate end
      points.

PMID- 18711428
TI  - Post-genomic challenges for collaborative research in infectious diseases.
AB  - Although high-burden pathogens have been prioritized for sequencing, genomic
      research has yet to yield effective vaccines, diagnostics or therapeutics for the
      infectious diseases that burden developing countries. International research
      partnerships are needed more today than ever before, and we propose that
      increased participation by scientists in endemic areas would overcome current
      roadblocks and is an essential path towards translational research outcomes.

PMID- 18711429
TI  - What really happens to dendritic cells during malaria?
AB  - As dendritic cells (DCs) initiate all adaptive and some innate immune responses,
      it is not surprising that DC function during malaria is the subject of intensive
      investigations. However, the results of these investigations have so far been
      controversial. Here, we discuss various aspects of these studies, including the
      influence of the species and strain of Plasmodium on DC function, the effects of
      Plasmodium infection on the activation of CD8(+) T cells by DCs, the effects of
      haemozoin and the effects of Plasmodium infections on DC Toll-like-receptor
      signalling.

PMID- 18711430
TI  - On the move.

PMID- 18711431
TI  - Chemokines and leukocyte traffic.
AB  - Twenty years after the discovery of chemokines is an appropriate time to review
      leukocyte traffic and to assess the knowledge and opportunities that have arisen
      from countless studies of the large and tight-knit family of chemotactic
      proteins.

PMID- 18711432
TI  - How chemokines invite leukocytes to dance.
AB  - A prominent activity of the chemokine system is the regulation of leukocyte
      trafficking. Here we summarize recent findings on the initial steps in chemokine
      receptor-induced signal transduction in leukocytes. In particular, we discuss the
      potential influences of the formation of oligomers of ligand and receptor and of
      coupling between chemokine signals and regulators of the cytoskeleton, such as
      small GTPases.

PMID- 18711433
TI  - Interstitial leukocyte migration and immune function.
AB  - The trafficking of leukocytes into and within lymphoid and peripheral tissues is
      central to immune cell development, immunosurveillance and effector function.
      Interstitial leukocyte trafficking is the result of amoeboid polarization and
      migration, guided by soluble or tissue-bound chemoattractant signals for
      positioning and local arrest. In contrast to other migration modes, amoeboid
      movement is particularly suited for scanning cellular networks and tissues. Here,
      we review mechanisms of leukocyte migration and sensing involved in diapedesis,
      tissue-based interstitial migration and egress, immune cell positioning in
      inflammation, and emerging therapeutic interference strategies.

PMID- 18711434
TI  - Orchestrating the orchestrators: chemokines in control of T cell traffic.
AB  - The understanding of how chemokines orchestrate the trafficking and activity of
      immune cells has increased considerably. So far, over 50 chemokines and 20
      chemokine receptors have been identified. Detailed analyses have demonstrated the
      function of chemokine receptors on T cell subsets, the temporal and spatial
      expression patterns of chemokines in vivo and the phenotypes of animals
      genetically deficient in one component or several components of the chemokine
      chemokine receptor system. New microscopy modalities for studying the influence
      of chemokines on the migratory activity of T cells in the lymph node have also
      brought new insights. Here we review such advances with particular emphasis on
      control of the migration of T cell subsets in lymph nodes and in peripheral
      tissues in homeostasis and inflammation.

PMID- 18711436
TI  - Moving targets: cell migration inhibitors as new anti-inflammatory therapies.
AB  - The pharmaceutical industry has targeted various types of molecules to subdue
      inflammatory diseases. Drugs that disrupt cell migration appear particularly
      promising in clinical trials and in many animal models of inflammatory disease.
      Cell migration inhibitors not only interfere with migration of cells to a tissue,
      but also can affect other necessary processes such as mediator release and
      angiogenesis. However, the question is whether drugs that target adhesion
      molecules or chemoattractant receptors will prove superior to drugs that target
      other molecular types. This review proclaims the virtues of targeting cell
      migration-related molecules for development of new anti-inflammatory and anti
      tumor based drugs. It is likely that cell migration inhibitors will transform the
      way in which many human inflammatory diseases and cancers are treated.

PMID- 18711435
TI  - Environmental cues, dendritic cells and the programming of tissue-selective
      lymphocyte trafficking.
AB  - Lymphocytes are imprinted during activation with trafficking programs
      (combinations of adhesion and chemoattractant receptors) that target their
      migration to specific tissues and microenvironments. Cytokines contribute, but,
      for gut and skin, evolution has cleverly adapted external cues from food (vitamin
      A) and sunlight (ultraviolet-induced vitamin D3) to imprint lymphocyte homing to
      the small intestines and T cell migration into the epidermis. Dendritic cells are
      essential: they process the vitamins to their active metabolites (retinoic acid
      and 1,25(OH)(2)D3) for presentation with antigen to lymphocytes, and they help
      export environmental cues through lymphatics to draining lymph nodes, to program
      the trafficking and effector functions of naive T and B cells.

PMID- 18711438
TI  - Tolerance can be infectious.
AB  - Studies focused on the goal of eliciting transplant tolerance led Herman Waldmann
      to rejuvenate discarded ideas of 'suppressor T cells'. Such cells are now known
      to exist.

PMID- 18711439
TI  - Building networks for immunodeficiency diseases and immunology training.
AB  - The RIKEN Research Center for Allergy and Immunology in Japan is reaching out
      regionally to the primary immunodeficiency disease community and internationally
      to graduate students and postdoctoral fellows.

PMID- 18711440
TI  - The making of NKT cells.

PMID- 18711441
TI  - The CD200-CD200R axis in local control of lung inflammation.

PMID- 18711442
TI  - Regulation of NKG2D ligands: a purposeful but delicate affair.

PMID- 18711443
TI  - A birthday gift for TRADD.

PMID- 18711446
TI  - Evidence for associations between PDE4D polymorphisms and a subtype of
      neuroticism.

PMID- 18711448
TI  - Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated
      degradation of IRF3.
AB  - Viral infection causes host cells to produce type I interferons (IFNs), which are
      critically involved in viral clearance. Previous studies have demonstrated that
      activation of the transcription factor interferon regulatory factor (IRF)3 is
      essential for virus-triggered induction of type I IFNs. Here we show that the E3
      ubiquitin ligase RBCC protein interacting with PKC1 (RBCK1) catalyzes the
      ubiquitination and degradation of IRF3. Overexpression of RBCK1 negatively
      regulates Sendai virus-triggered induction of type I IFNs, while knockdown of
      RBCK1 has the opposite effect. Plaque assays consistently demonstrate that RBCK1
      negatively regulates the cellular antiviral response. Furthermore, viral
      infection leads to induction of RBCK1 and subsequent degradation of IRF3. These
      findings suggest that the cellular antiviral response is controlled by a negative
      feedback regulatory mechanism involving RBCK1-mediated ubiquitination and
      degradation of IRF3.

PMID- 18711449
TI  - CJO: the baton is passed.

PMID- 18711447
TI  - The evolution and functional diversification of animal microRNA genes.
AB  - microRNAs (miRNAs) are an abundant class of approximately 22 nucleotide (nt)
      regulatory RNAs that are pervasive in higher eukaryotic genomes. In order to
      fully understand their prominence in genomes, it is necessary to elucidate the
      molecular mechanisms that can diversify miRNA activities. In this review, we
      describe some of the many strategies that allow novel miRNA functions to emerge,
      with particular emphasis on how miRNA genes evolve in animals. These mechanisms
      include changes in their sequence, processing, or expression pattern; acquisition
      of miRNA* functionality or antisense processing; and de novo gene birth. The
      facility and versatility of miRNAs to evolve and change likely underlies how they
      have become dominant constituents of higher genomes.

PMID- 18711450
TI  - Ontario recognizes low-vision rehabilitation.

PMID- 18711452
TI  - Self-reported visual impairment in elderly Canadians and its impact on healthy
      living.
AB  - BACKGROUND: Using a nationwide sample from community- and institution-dwelling
      residents, we describe the prevalence of self-reported visual impairment in
      elderly Canadians and examine its association with selected social demographics
      and health factors. METHODS: Subjects were participants in the phase I clinical
      examination of the Canadian Study of Health and Aging. Vision state was
      ascertained from a self-reported question: "How is your eyesight (with glasses or
      contacts if you wear them)?" A response of "poor" (referred to as poor vision) or
      "unable to see" (referred to as blindness) was considered visual impairment.
      Other information was from in-person interviews or clinical examinations.
      Standardized weights were used in all analyses. RESULTS: Analyses included 2671
      participants with a median age of 72 years. The overall prevalence was 6.2% for
      poor vision, 0.7% for blindness, and 6.8% for either. A higher prevalence was
      seen in women and in people aged 85 years or older. Participants with < or = 6
      years of education were approximately 2 times more likely to report visual
      impairment. Institutional residents and people with falls or a depressed mood
      were approximately 3 times more likely to state visual impairment. Smoking was
      associated with approximately 4 times higher odds of visual impairment, while
      persons presenting difficulty with everyday activities or with self-rated poor
      health were approximately 7 and 15 times more likely to report visual impairment.
      INTERPRETATION: Visual impairment in elderly Canadians is common and is
      associated with increased odds of institutionalization, frequent falls,
      difficulty with everyday activities, and poor health. Good eyesight may imply
      good health and good independence in the elderly.

PMID- 18711453
TI  - Canadian research contributions to low-vision rehabilitation.
AB  - BACKGROUND: Demographic changes likely to occur in the near future and the need
      for planning to address them are behind the urgent drive to assess present-day
      provision and utilization of low-vision rehabilitation (LVR) services in the
      community. Perhaps even more important is the assessment of supporting research
      work in this field of health care. The purpose of this study, therefore, was to
      investigate the current involvement of researchers in Canada in the elucidation
      of the LVR sciences. METHODS: A PubMed search of the MEDLINE database was
      performed. Publications were identified according to preset criteria and search
      key words pertinent to various aspects of LVR sciences. Data were collected on
      the corresponding authors and their affiliations, type of journal and type of
      study performed, and reported outcome measures. RESULTS: Approximately 1500
      papers were reviewed, and 131 that met the preset criteria were included in the
      study. Medical doctors published most papers (48.1%), followed by optometrists,
      those with PhDs, occupational therapists, and others; most of the papers (44.3%)
      were published in ophthalmology journals. Research was performed mainly at
      Canadian universities (84%), and the findings were published in the last 3
      decades. The studies largely concentrated on rehabilitation services and other
      aspects of vision rehabilitation (55%), whereas studies focusing on the
      evaluation of tools used for assessment of either visual functions or functional
      vision were in the minority (45%). INTERPRETATION: The majority of research
      activity in Canada is university based and involves the medical profession in a
      leading role, thus affording LVR the appropriate medium for promotion and
      development of a multidisciplinary approach to outstanding research issues. Only
      a fraction of current research in LVR (12.2%) deals with outcome measures of the
      therapeutic interventions aimed at restoring functional vision.

PMID- 18711454
TI  - Should ophthalmologists receive communication skills training in breaking bad
      news?
AB  - BACKGROUND: Effective communication is essential in the delivery of health care.
      The purpose of the present study was to determine whether formal communication
      skills training in breaking bad news should be incorporated into the training of
      ophthalmologists. METHODS: An online survey was offered to every member of the
      Canadian Ophthalmological Society (COS) with a registered email address. Survey
      questions focused on 2 specific scenarios: (S1) disclosing permanent vision loss
      to a patient and (S2) revoking a patient's driver's licence. Main outcome
      measures were the respondents' opinions on the need for and benefit of including
      communication skills in the training of ophthalmologists and, if considered
      necessary, its optimal format and point in their training. RESULTS: The response
      rate was 28% (225/800). The vast majority of respondents believed that it is
      important for ophthalmologists to be able to communicate effectively when
      breaking bad news (S1: 99%, mean Likert score 4.81; S2: 97%, 4.73); that
      communication skills training would be beneficial in breaking bad news for both
      future ophthalmologists (S1: 88%, 4.28; S2: 87%, 4.24) and patients (S1: 92%,
      4.26; S2: 87%, 4.24); and that it should be included in the training of
      ophthalmologists (S1: 87%, 4.27; S2: 83%, 4.15). Residency was the preferred
      point in training (95% for both scenarios), but there was no consensus on what
      type of training format(s) to use. INTERPRETATION: Survey respondents strongly
      support the inclusion during ophthalmology residency of formal communication
      skills training in breaking bad news. This would be a logical choice of content
      for ophthalmology residency programs striving to meet the mandated "interpersonal
      and communication skills" core competency requirements.

PMID- 18711455
TI  - Causes of blindness among children identified through village key informants in
      Malawi.
AB  - BACKGROUND: To determine the causes of blindness among children in rural Malawi.
      METHODS: This was a cross-sectional study of children in communities of Chikwawa
      district, Malawi. Children were identified through trained, community-based key
      informants. All identified children were examined by an ophthalmologist and the
      cause of blindness determined. RESULTS: In total, 151 children were identified,
      of whom 37 (25%) were blind. Among the blind, 21 (60%) were girls and 16 (40%)
      were boys. Cataract (congenital/developmental) was the leading cause of blindness
      (35%), followed by corneal conditions (22%). INTERPRETATION: In an area once
      noted for vitamin A deficiency in children, cataract is now the leading cause of
      blindness in children, replacing cornea blindness. Priorities for early cataract
      detection and intervention need to be considered for restoration of sight in
      children.

PMID- 18711456
TI  - Tranexamic acid in the treatment of pediatric traumatic hyphema.
AB  - BACKGROUND: This study was undertaken to determine whether a difference exists in
      treatment outcome between patients treated with tranexamic acid (TEA) plus
      topical steroids and those treated with topical steroids alone. METHODS: A
      retrospective cohort study was conducted to compare treatment results for
      children with traumatic hyphema treated with TEA and topical steroids versus
      topical steroids alone. Patients were identified from a chart review of the
      Children's Hospital of Eastern Ontario eye clinic and the Queen's Department of
      Ophthalmology emergency eye clinic for charts coded "traumatic hyphema." The
      primary outcomes measured included visual acuity, rebleed rate, intraocular
      pressure, and time to hyphema resolution. Covariates were hyphema grade, the need
      for medications to lower intraocular pressure, and the presence of associated
      ocular traumatic complications. Analysis was performed with both bivariate
      analysis and multivariate models. RESULTS: Two hundred and fifteen patients with
      traumatic hyphema were included in our study. One hundred and thirty-seven
      patients (63.1%) received TEA plus topical steroids, and the remaining 78
      patients received topical steroids alone. There was no significant difference in
      rebleed rate between the TEA plus topical steroid group (1.6%) and the steroid
      alone group (2.6%, p = 0.60). INTERPRETATION: Patients with traumatic hyphema
      treated with TEA plus topical steroids did not have a significantly lower
      incidence of rebleed than those treated with topical steroids alone.

PMID- 18711457
TI  - Characteristics of patients presenting with ocular pain.
AB  - BACKGROUND: The purpose of this study was to assess the utility of neuroimaging
      in patients with normal neuro-ophthalmic examinations referred to a neuro
      ophthalmology clinic for complaints of chronic isolated eye pain. We were also
      interested in the prevalence of primary headache syndromes in these patients,
      particularly medication overuse headache (MOH). METHODS: Charts of 125
      consecutive patients referred to a neuro-ophthalmology clinic with some form of
      head or facial pain were reviewed to find patients meeting the criteria of having
      complaints of chronic eye with normal neuro-ophthalmic examinations. Excluded
      were patients with primary complaint other than eye pain. A single examiner
      performed all examinations in a standardized fashion. Each patient was queried
      about the use of prescription and over-the-counter analgesics. RESULTS: Seventy
      three percent of patients had some form of primary headache syndrome, and 21% of
      patients had some component of probable MOH. Another 4.5% had a presumed
      component of medication overuse. None of those who received imaging had any
      results explaining the ocular pain. INTERPRETATION: Primary headache is present
      in most patients with chronic, isolated ocular pain. MOH is common and probably
      underrecognized in this population. It needs to be addressed if the patient is
      ever to be pain free. Neuroimaging has very low yield in this group of
      subspecialty referral patients.

PMID- 18711458
TI  - Repeatability of the multifocal visual evoked potentials in a clinical glaucoma
      setting.
AB  - BACKGROUND: To determine the reproducibility of the multifocal visual evoked
      potentials (mfVEP) test results in a clinical glaucoma setting, and the factors
      that affect variability. METHODS: This was an observational case series study.
      The monocular mfVEP test, having a 58-sector, pattern-reversal dartboard array,
      was performed twice within 4 weeks in both eyes of 29 adult open-angle glaucoma
      (OAG) patients and suspects, using AccuMap Opera Software (ObjectiVision Pty Ltd,
      Sydney, Australia). The AccuMap severity index (ASI), the mean amplitude, and the
      individual amplitudes in each sector were compared between the 2 tests using
      intraclass correlations (ICCs). The effects of the severity of mfVEP field
      defects and signal-to-noise ratio (SNR) on the reproducibility of these variables
      were determined using the McNemar test and the Spearman rank correlation,
      respectively. RESULTS: The average ICCs of the ASI and amplitudes in the 2 tests
      were 0.84 and 0.87, respectively. Two sectors in the right eye and 6 in the left
      eye had significant differences between the 2 tests (Wilcoxon signed-rank p <
      0.05). Larger differences were observed in patients having lower SNR (Spearman p
      = 0.022). Forty-six of the 58 eyes stayed within the same diagnosis category on
      repeating the test (i.e., within normal limits or outside normal limits).
      INTERPRETATION: Although there were some isolated examples of clinically
      significant differences on repeating the mfVEP test in our patients, our results
      suggest overall good repeat reliability. The variability of the test was higher
      in patients having high noise levels during the test.

PMID- 18711459
TI  - Suspected giant cell arteritis: a study of referrals for temporal artery biopsy.
AB  - BACKGROUND: The purpose of this study is to describe the nature of cases
      undergoing temporal artery biopsy (TAB) for suspected giant cell arteritis (GCA).
      METHODS: A retrospective review of case notes was undertaken for all patients on
      whom ophthalmologists had performed TAB in 2 teaching hospitals between 1995 and
      2001. Presenting symptoms, referring specialty, TAB result, treatment, and
      discharge diagnosis were recorded. RESULTS: Ophthalmologists performed TAB on 110
      patients for suspected GCA. A variety of specialties referred patients to
      ophthalmology for TAB; presenting symptoms varied with referral source. Of the
      110 TABs, 21 (19%) were reported as positive for GCA, 84 (76%) were negative, and
      5 (4.5%) were reported as inadequate. The symptoms most commonly associated with
      a positive TAB were visual disturbance (15/21) and headache (15/21). The odds
      ratios for having a positive TAB result rather than a negative result were 1.0
      for the presence of headache, 4.1 for visual disturbance, and 6.7 for jaw
      claudication. INTERPRETATION: Physicians were faced with a different population
      of GCA suspects than ophthalmologists. While physicians should be alert to the
      significance of visual symptoms or jaw claudication, ophthalmologists should be
      ready to facilitate prompt TABs when appropriate. TAB should be performed
      promptly and an adequate length of artery taken for biopsy. An argument can be
      made that TAB is not needed in cases of suspected GCA. However, a positive result
      provides firm justification for the use of steroids. We feel that TAB has a
      useful role and we make reference to methods to maximize its usefulness.

PMID- 18711460
TI  - Glaucoma laser and surgical procedure rates in Canada: a long-term profile.
AB  - BACKGROUND: New laser and surgical techniques have had a significant effect on
      glaucoma therapy. A precise understanding of how these developments are affecting
      overall glaucoma management is fundamental to health services planning. The
      objective of this study was to synthesize Canadian national and provincial data
      regarding glaucoma laser and surgical procedure rates from 1992 to 2004. METHODS:
      Canadian provincial health insurance databases, which cover virtually all
      surgical procedures provided domestically to Canadians, were accessed to
      ascertain yearly total glaucoma procedure numbers. To estimate the number of
      individuals with glaucoma, an age-stratified glaucoma prevalence model was
      applied to population census data. RESULTS: Laser trabeculoplasty rates
      dramatically increased between 2001 and 2004 with the national Canadian rate more
      than doubling. However, this increase varied widely across regions, ranging from
      0% to 530%. Trabeculectomy surgery rates slowly increased from 1992 to 1995, then
      declined by 29% nationally between 1995 and 2004. Implantation rates of glaucoma
      drainage devices increased 12-fold nationally between 1992 and 2004; by 2004 this
      procedure accounted for 10% of incisional glaucoma surgical procedures in Canada.
      INTERPRETATION: In Canada, laser trabeculoplasty rates have risen significantly
      over recent years. Trabeculectomy rates have recently declined, and implantation
      of glaucoma drainage devices is playing an increasingly important role in
      glaucoma management in this country.

PMID- 18711461
TI  - Multicenter study of compliance and drop administration in glaucoma.
AB  - BACKGROUND: Poor compliance with medication is a major concern in the management
      of glaucoma. Improper administration technique can lead to contamination and
      inaccurate dosing. This study estimates the prevalence and predictors of
      noncompliance and improper administration technique among Canadian glaucoma
      patients. METHODS: Data were collected using a standardized questionnaire.
      Noncompliance was defined as missing at least 1 drop of medication per week and
      (or) the inability to accurately describe the medication regimen. Patients were
      asked to indicate the most common reason for missing medication. Study personnel
      assessed drop administration technique as patients were applying eye drops.
      Physicians provided information, including measures of disease stability,
      regarding the patient's glaucoma. Predictors were assessed using odds ratios from
      a logistic regression model. RESULTS: 500 patients from 10 centers across Canada
      participated in the study. Of these, 25.6% reported missing at least 1 drop of
      medication per week, and 4.2% were unable to accurately describe their medication
      regimen. The overall proportion of noncompliance was 27.9%. With regard to drop
      administration, 6.8% missed their eye and 28.8% contaminated the bottle tip;
      overall, 33.8% demonstrated improper technique. The most common reasons given for
      missing eye drops were "forgetfulness" and "being away from drops." Formal
      education limited to elementary school and treatment duration of <5 years
      increased patient-reported noncompliance. Factors associated with improper
      administration technique were age 60 years and older and formal education limited
      to elementary school. INTERPRETATION: Over 50% of the patients surveyed were
      either noncompliant or demonstrated improper administration technique. Glaucoma
      patients should be educated on the importance of compliance and instructed on
      proper drop administration.

PMID- 18711462
TI  - Ahmed glaucoma valve implantation in uveitic glaucoma versus open-angle glaucoma
      patients.
AB  - BACKGROUND: The poor long-term success rate of repeat trabeculectomies in
      refractory uveitic glaucoma (UG) patients has led to the use of glaucoma drainage
      devices (GDDs). However, the success and complication rates of GDDs in UG
      patients utilizing a control group with standard demographic data, design, and
      surgical technique have never been evaluated. METHODS: Fifteen patients (15 eyes)
      with chronic uveitis and 53 patients (53 eyes) with uncontrolled open-angle
      glaucoma (OAG) who underwent Ahmed glaucoma valve (AGV) implantation were
      included in a retrospective, comparative, case-controlled study. Postoperative
      intraocular pressure (IOP), number of antiglaucoma medications, visual acuity,
      and complications were compared. RESULTS: There was a significant difference
      between the UG versus the OAG group with respect to age only (59.3 years vs 68.4
      years, p = 0.006). Regression analysis of the postoperative IOP controlled for
      age and glaucoma type, and preoperative IOP revealed significantly lower IOP in
      the UG group at 1 month (p = 0.04; 95% confidence interval [CI] -5.9 to 0.15) and
      2 months (p = 0.008; 95% CI -6.0 to 0.97). No significant differences were found
      at 3, 6, 12, 24, and 30 months. The cumulative success rates at 3 to 30 months
      for the UG and OAG groups were 80% to 66.6% versus 84.9% to 57% (p = 0.713),
      respectively. The only complication between the 2 groups that was significantly
      different was tube removal, which occurred more often in the UG group (p =
      0.018). INTERPRETATION: AGV implantation is an effective and safe procedure in
      the management of UG, similar to primary OAG.

PMID- 18711463
TI  - Behcet's disease: comparing 3 decades of treatment response at the National Eye
      Institute.
AB  - BACKGROUND: The goal of the present study was to analyze differences in response
      to the treatment of ocular Behcet's disease (BD) in the 1960s, 1980s, and 1990s.
      METHODS: Medical records of 120 patients with uveitis due to BD followed at the
      National Eye Institute, National Institutes of Health, from 1962 to 2004, were
      reviewed. RESULTS: The patients were categorized into 3 groups according to the
      time of follow-up: the first group was followed from 1962 until 1972, the second
      group from 1983 until 1992, and the third group from 1992 through 2004. Snellen
      visual acuity was converted to logMAR values. The range of values for
      inflammation was 0.5 (trace), 1 (mild), 2 (moderate), and 3 (severe). There were
      45 patients (89 affected eyes) in the 1960s group, 26 patients (52 eyes) in the
      1980s group, and 49 patients (94 eyes) in the most recent group. Statistical
      analysis showed that the mean logMAR score decreased with each decade. Mean
      visual acuity in the 1990s group was significantly better than in the previous
      decades (p < 0.001 for the 1960s group and p = 0.019 for the 1980s). The mean
      inflammation score was significantly higher in the 1960s than in the subsequent
      decades (p < 0.001 both for the 1980s and for the 1990s). INTERPRETATION: BD is a
      severe, blinding disorder. There was a definitive trend toward improvement in
      clinical outcome from the 1960s to 1990s. We attribute this trend to the
      introduction of newer, more potent corticosteroid-sparing agents and targeted
      therapy.

PMID- 18711464
TI  - Evaluation of serum resistin levels in patients with ocular and non-ocular
      Behcet's disease.
AB  - BACKGROUND: Resistin, a recently identified adipocytokine, has been found to play
      an important role in inflammation and the processes of inflammation-related
      diseases. Serum resistin levels in patients with Behcet's disease (BD) have not
      yet been investigated. We aimed to evaluate the relation between resistin and
      interleukin-6 (IL-6) in Behcet patients with or without ocular involvement and in
      normal controls. METHODS: Twenty-two patients with BD and 19 healthy control
      subjects were included in this study. While 14 patients had posterior segment
      involvement of the eye, the other 8 did not have ocular disease. Serum resistin
      and interleukin-6 (IL-6), levels were measured in all samples. Data from all
      groups were tested for statistical significance. RESULTS: The mean resistin and
      IL-6 concentrations were significantly higher in patients with BD than the
      control subjects (p = 0.011 and p = 0.0001, respectively). There was a
      significant difference in resistin and IL-6 levels between the patients with non
      ocular BD and controls (p = 0.013 and p = 0.0001, respectively), as well as
      resistin and IL-6 levels between the ocular BD group and the control group (p =
      0.05 and p = 0.0001, respectively). However, there was no significant difference
      between patients with ocular versus non-ocular BD. INTERPRETATION: Resistin
      levels were found to be raised in Behcet patients with or without ocular
      involvement compared with the control subjects.

PMID- 18711465
TI  - Conjunctival flora in Behcet patients.
AB  - BACKGROUND: To determine the difference in conjunctival flora in Behcet patients
      compared with the normal population. METHODS: This study was carried out on a
      study group of 50 patients in the inactive period of Behcet's disease and a
      control group of 50 age- and sex-matched healthy subjects with no systemic or
      ocular disease. A swab was taken from the lower fornix using a sterile swab and
      inoculated into bloody eosin methylene blue, chocolate, and Sabouraud dextrose
      agar media. RESULTS: The mean age was 36.04 (SD 2.16) years for the Behcet group
      and 35.64 (SD 1.96) years for the control group. Bacterial growth was observed in
      92% (n = 46) of the Behcet group and 56% (n = 29) of the control group. The
      Behcet group results were Staphylococcus aureus in 12 (24%), coagulase negative
      staphylococci (CNS) in 32 (64%), Moraxella spp in 8 (16%), Streptococcus spp in 8
      (16%), Bacillus spp in 4 (8%), Neisseria spp in 4 (8%), Candida spp in 3 (6%),
      and Haemophilus spp in 1 (2%). In the control group, the results were S. aureus
      in 2 (4%), CNS in 24 (48%), Moraxella spp in 2 (4%), Streptococcus spp in 1 (2%),
      Bacillus spp in 3 (6%), Neisseria spp in 3 (6%), and Candida spp in 1 (2%).
      INTERPRETATION: S. aureus, Moraxella spp, and Streptococcus spp colonization was
      significantly higher in the conjunctival flora of Behcet patients than in that of
      the control group. A bacterial etiology may be involved in the pathogenesis of
      Behcet's disease.

PMID- 18711466
TI  - Generalized posterior keratoconus: clinical pathologic correlations.
AB  - CASE REPORT: A 73-year-old woman presented with bilateral generalized posterior
      keratoconus. The corneal thickness measured 0.320 mm paracentrally and 0.440 mm
      toward the periphery. The corneal specimen revealed absence of Bowman's layer and
      focal homogeneous oval stromal deposits that stained for amyloid. COMMENTS: Our
      case of generalized posterior keratoconus shows absence of Bowman's layer. The
      amyloid deposits, which also were noted clinically in the cornea of the fellow
      right eye, were most consistent with a diagnosis of polymorphous amyloid
      degeneration. To our knowledge, this is the first histopathological report of
      generalized posterior keratoconus.

PMID- 18711468
TI  - Combined retinal detachment in proliferative diabetic retinopathy.

PMID- 18711469
TI  - Corneal curvature and central corneal thickness in a population-based sample of
      eyes with pseudoexfoliation syndrome-Reykjavik Eye Study.

PMID- 18711470
TI  - Diabetes as a possible predisposer for blepharitis.

PMID- 18711471
TI  - A unique presentation of bilateral central serous chorioretinopathy following
      bilateral renal transplantation surgery.

PMID- 18711472
TI  - Cortical visual loss consequent to brain metastases from an endometrial
      carcinoma.

PMID- 18711473
TI  - Subfoveal choroidal neovascularization associated with cytomegalovirus retinitis
      and AIDS.

PMID- 18711474
TI  - Intravitreal bevacizumab compared with photodynamic therapy with verteporfin for
      group 2a parafoveal retinal telangiectasis.

PMID- 18711475
TI  - Diffuse leukoencephalitis associated with retinoblastoma: case report of a
      presumed paraneoplastic syndrome.

PMID- 18711476
TI  - Intravitreal pegaptanib reduces fluorescein leakage in idiopathic parafoveal
      telangiectasis.

PMID- 18711477
TI  - Ocular findings in yellow nail syndrome.

PMID- 18711479
TI  - Improving image quality of diffuse optical tomography with a projection-error
      based adaptive regularization method.
AB  - Diffuse optical tomography (DOT) reconstructs the images of internal optical
      parameter distribution using noninvasive boundary measurements. The image
      reconstruction procedure is known to be an ill-posed problem. In order to solve
      such a problem, a regularization technique is needed to constrain the solution
      space. In this study, a projection-error-based adaptive regularization (PAR)
      technique is proposed to improve the reconstructed image quality. Simulations are
      performed using a diffusion approximation model and the simulated results
      demonstrate that the PAR technique can improve reconstruction precision of object
      more effectively. The method is demonstrated to have low sensitivity to noise at
      various noise levels. Moreover, with the PAR method, the detectability of an
      object located both at the center and near the peripheral regions has been
      increased largely.

PMID- 18711480
TI  - Elemental analysis using micro laser-induced breakdown spectroscopy (microLIBS)
      in a microfluidic platform.
AB  - We present here a non-labeled, elemental analysis detection technique that is
      suitable for microfluidic chips, and demonstrate its applicability with the
      sensitive detection of sodium (Na). Spectroscopy performed on small volumes of
      liquids can be used to provide a true representation of the composition of the
      isolated fluid. Performing this using low power instrumentation integrated with a
      microfluidic platform makes it potentially feasible to develop a portable system.
      For this we present a simple approach to isolating minute amounts of fluid from
      bulk fluid within a microfluidic chip. The chip itself contains a patterned thin
      film resistive element that super-heats the sample in tens of microseconds,
      creating a micro-bubble that extrudes a micro-droplet from the microchip. For
      simplicity a non-valved microchip is used here as it is highly compatible to a
      continuous flow-based fluidic system suitable for continuous sampling of the
      fluid composition. We believe such a nonlabeled detection technique within a
      microfluidic system has wide applicability in elemental analysis. This is the
      first demonstration of laser-induced breakdown spectroscopy (LIBS) as a detection
      technology in conjunction with microfluidics, and represents first steps towards
      realizing a portable lower power LIBS-based detection system.

PMID- 18711481
TI  - Optical dissection of stimulus-evoked retinal activation.
AB  - Better understanding of stimulus-evoked intrinsic optical signals (IOSs) in the
      retina promises new methodology for study and diagnosis of retinal function.
      Using a flood-illumination near infrared (NIR) light microscope equipped with
      high-speed CCD (80 Hz) and CMOS (1000 Hz) cameras, we validated depth-resolved
      enface imaging of fast IOSs in isolated retina of leopard frog. Both positive
      (increasing) and negative (decreasing) IOSs were observed at the photoreceptor
      and inner layers of the retina. The distribution of IOSs with opposite polarities
      showed a center-surround pattern. At the photoreceptor layer, negative IOSs
      dominated the center area illuminated by the stimulus light spot, while positive
      signals dominated the surrounding area. In contrast, at inner retinal layers,
      positive IOSs dominated the center area covered by the stimulus light spot, and
      negative IOSs were mainly observed in the surrounding area. Fast CMOS imaging
      disclosed rapid IOSs within 5 ms after the stimulus onset, and both ON and OFF
      optical responses were observed associated with a step light stimulus.

PMID- 18711482
TI  - Stable source of high quality telecom-band polarization-entangled photon-pairs
      based on a single, pulse-pumped, short PPLN waveguide.
AB  - We demonstrate a stable source of high quality telecom-band polarization
      entangled photon-pairs based on a single, pulse-pumped, short periodically-poled
      lithium niobate (PPLN) waveguide. Full quantum state tomographic measurement
      performed on the photon-pairs has revealed a very high state purity of 0.94, and
      an entanglement fidelity exceeding 0.96 at the low-rate-regime. At higher rates,
      entanglement quality degrades due to emission of multiple-pairs. Using a new
      model, we have confirmed that the observed degradation is largely due to double-
      and triple-pair emissions.

PMID- 18711483
TI  - Plasmonic band gap structures for surface-enhanced Raman scattering.
AB  - Surface-enhanced Raman Scattering (SERS) of rhodamine 6G (R6G) adsorbed on
      biharmonic metallic grating structures was studied. Biharmonic metallic gratings
      include two different grating components, one acting as a coupler to excite
      surface plasmon polaritons (SPP), and the other forming a plasmonic band gap for
      the propagating SPPs. In the vicinity of the band edges, localized surface
      plasmons are formed. These localized plasmons strongly enhance the scattering
      efficiency of the Raman signal emitted on the metallic grating surfaces. It was
      shown that reproducible Raman scattering enhancement factors of over 10(5) can be
      achieved by fabricating biharmonic SERS templates using soft nano-imprint
      technique. We have shown that the SERS activities from these templates are
      tunable as a function of plasmonic resonance conditions. Similar enhancement
      factors were also measured for directional emission of photoluminescence. At the
      wavelengths of the plasmonic absorption peak, directional enhancement by a factor
      of 30 was deduced for photoluminescence measurements.

PMID- 18711484
TI  - Integration of hybrid silicon lasers and electroabsorption modulators.
AB  - We present an integration platform based on quantum well intermixing for multi
      section hybrid silicon lasers and electroabsorption modulators. As a
      demonstration of the technology, we have fabricated discrete sampled grating DBR
      lasers and sampled grating DBR lasers integrated with InGaAsP/InP
      electroabsorption modulators. The integrated sampled grating DBR laser-modulators
      use the as-grown III-V bandgap for optical gain, a 50 nm blue shifted bandgap for
      the electrabosprtion modulators, and an 80 nm blue shifted bandgap for low loss
      mirrors. Laser continuous wave operation up to 45 ?C is achieved with output
      power >1.0 mW and threshold current of <50 mA. The modulator bandwidth is >2GHz
      with 5 dB DC extinction.

PMID- 18711485
TI  - Interaction of nanoparticles with substrates: effects on the dipolar behaviour of
      the particles.
AB  - In this work, we present a numerical analysis of the surface electric field of a
      metallic nanoparticle (either 2D or 3D) interacting with a flat substrate
      underneath. The influence of the distance to the substrate, particle size, the
      surrounding media and the substrate optical properties is analyzed as a function
      of the incident wavelength. We show that these are crucial factors that change
      the field distribution associated to the dipolar behavior of the particle. A
      useful parameter for illustrating the changes in the angular distribution is
      theta(max), the angle at which the maximum of the surface electric field is
      located.

PMID- 18711486
TI  - Observation of quantum interference between a single-photon state and a thermal
      state generated in optical fibers.
AB  - We experimentally demonstrate a Hong-Ou-Mandel type of two-photon interference
      effect with a heralded single-photon state and a thermal state. The light sources
      in the 1550 nm telecom band are generated from two independent dispersion-shifted
      fibers via four-wave mixing process. The observed visibility is (82+/- 11)%. This
      type of interference between independent sources is crucial in quantum
      information process with independent qubits.

PMID- 18711487
TI  - Sensitive label-free biosensing using critical modes in aperiodic photonic
      structures.
AB  - In this paper, we introduce a novel approach for optical sensing based on the
      excitation of critically localized modes in two-dimensional deterministic
      aperiodic structures generated by a Rudin-Shapiro (RS) sequence. Based on a
      rigorous computational analysis, we demonstrate that RS photonic structures
      provide a large number of resonant modes better suited for sensing applications
      compared to traditional band-edge and defect-localized modes in periodic photonic
      structures. Finally, we show that enhanced sensitivity to refractive index
      variations as low as (delta)n=0.002 in RS structures results from the extended
      nature of critical modes and can enable the fabrication of novel label-free
      optical biosensors.

PMID- 18711488
TI  - Purcell effect in nonlinear photonic structures: a coupled mode theory analysis.
AB  - We develop a coupled mode theory (CMT) model of the behavior of a polarization
      source in a general photonic structure, and obtain an analytical expression for
      the resulting generated electric field; loss, gain and/or nonlinearities can also
      be modeled. Based on this treatment, we investigate the criteria needed to
      achieve an enhancement in various nonlinear effects, and to produce efficient
      sources of terahertz radiation, in particular. Our results agree well with exact
      finite-difference time-domain (FDTD) results. Therefore, this approach can also
      in certain circumstances be used as a potential substitute for the more
      numerically intensive FDTD method.

PMID- 18711489
TI  - Coupled optical microcavities: an enhanced refractometric sensing configuration.
AB  - We theoretically investigate the application of coupled optical microcavities as
      refractive index sensors. Coupled microcavities support a very sharp asymmetrical
      Fano resonance, which gives rise to faster changes in output transmission than
      the changes from a single cavity. With the output transmission at a fixed
      wavelength that varies much faster than it does in a single-cavity resonance, the
      result is enhanced sensitivity of the device to the changes in refractive index.
      In addition, it is observed that both thermal and optical Kerr effects can be
      utilized to improve the sensitivity.

PMID- 18711490
TI  - Polarization independent 4-stage OTDM multiplexer using plated GRIN lens.
AB  - In this paper, a 4-stage optical time domain multiplexing (OTDM) multiplexer
      based on plated graded index (GRIN) lens is proposed and experimentally
      demonstrated. A 10Gbit/s return-to-zero (RZ) signal is upgraded to 160Gbit/s. The
      time-domain accuracy of the multiplexer is evaluated by analyzing the multiplexed
      160Gbit/s signal. Experimental results validate the stability of the optical
      multiplexing behavior and the polarization insensitivity of the proposed
      multiplexer. The results also show the advantages of our OTDM multiplexer such as
      the flexible output signal speeds at the output of different stages, the low
      insertion loss and the temperature and wavelength stability.

PMID- 18711491
TI  - Analysis of the possibility of analog detectors calibration by exploiting
      stimulated parametric down conversion.
AB  - Spontaneous parametric down conversion (SPDC) has been largely exploited as a
      tool for absolute calibration of photon-counting detectors, i.e detectors
      registering very small photon fluxes. In [J. Opt. Soc. Am. B 23, 2185 (2006)] we
      derived a method for absolute calibration of analog detectors using SPDC emission
      at higher photon fluxes, where the beam is seen as a continuum by the detector.
      Nevertheless intrinsic limitations appear when high-gain regime of SPDC is
      required to reach even larger photon fluxes. Here we show that stimulated
      parametric down conversion allow one to avoid this limitation, since stimulated
      photon fluxes are increased by the presence of the seed beam.

PMID- 18711492
TI  - Optical chirality without optical activity: How surface plasmons give a twist to
      light.
AB  - Light interacts differently with left and right handed three dimensional chiral
      objects, like helices, and this leads to the phenomenon known as optical
      activity. Here, by applying a polarization tomography, we show experimentally,
      for the first time in the visible domain, that chirality has a different optical
      manifestation for twisted planar nanostructured metallic objects acting as
      isolated chiral metaobjects. Our analysis demon-strate how surface plasmons,
      which are lossy bidimensional electromagnetic waves propagating on top of the
      structure, can delocalize light information in the just precise way for giving
      rise to this subtle effect.

PMID- 18711493
TI  - Low-threshold, narrow-line THz-wave parametric oscillator with an intra-cavity
      grazing-incidence grating.
AB  - We report a low-threshold, narrow-line THz-wave parametric oscillator with an
      intra-cavity grazing-incidence grating and a 1-mm thick, 45-mm long lithium
      niobate planar waveguide. When pumped by an actively Q-switched Nd:YAG laser, the
      threshold energy and intensity of the parametric oscillator were about 2.2 mJ and
      70 MW/cm(2), respectively. The linewidths of the output THz wave were 12 and 134
      GHz with and without the intra-cavity grating, respectively.

PMID- 18711494
TI  - Ultrasound-modulated optical imaging using a powerful long pulse laser.
AB  - Ultrasound-modulated optical imaging (or tomography) is an emerging biodiagnostic
      technique which provides the optical spectroscopic signature and the localization
      of an absorbing object embedded in a strongly scattering medium. We propose to
      improve the sensitivity of the technique by using a pulsed single-frequency laser
      to raise the optical peak power applied to the scattering medium and thereby
      collect more ultrasonically tagged photons. Moreover, when the detection of
      tagged photons is done with a photorefractive interferometer, the high optical
      peak power reduces the response time of the photorefractive crystal below the
      speckle field decorrelation time. Results obtained with a GaAs photorefractive
      interferometer are presented for 30- and 60-mm thick scattering media.

PMID- 18711495
TI  - Modal properties and thermal behaviors of high quality factor quasi-photonic
      crystal microcavity.
AB  - We investigate the variations of modal properties of 12-fold quasi-photonic
      crystal microcavities sustaining whispering-gallery (WG) mode with different
      central post sizes both in simulations and experiments. We realize our design by
      a series of dry- and wet-etching processes. WG mode lasing actions are obtained
      with high quality (Q) factor of 8,400 from microcavity with effective post size
      420 nm in diameter. Loss and thermal behaviors are analyzed by measured Q
      factors, thresholds, and rolling-off effects from light-in light-out curves of
      microcavities with increased post size. By finite-element simulations, we also
      address the heat sink improvement due to presence of larger central post that is
      observed in measurements.

PMID- 18711496
TI  - Enhancement of optical Kerr effect in quantum-cascade lasers with multiple
      resonance levels.
AB  - In this paper, we investigated the optical Kerr lensing effect in quantum-cascade
      lasers with multiple resonance levels. The Kerr refractive index n2 is obtained
      through the third-order susceptibility at the fundamental frequency chi(3)(
      omega; omega, omega,-omega). Resonant two-photon processes are found to have
      almost equal contributions to chi(3)( omega; omega, omega,-omega) as the single
      photon processes, which result in the predicted enhancement of the positive
      nonlinear (Kerr) refractive index, and thus may enhance mode-locking of quantum
      cascade lasers. Moreover, we also demonstrate an isospectral optimization
      strategy for further improving n2 through the band-structure design, in order to
      boost the multimode performance of quantum-cascade lasers. Simulation results
      show that the optimized stepwise multiple-quantum-well structure has n2
      approximately 10-8 cm2/W, a twofold enhancement over the original flat quantum
      well structure. This leads to a refractive-index change (delta)n of about 0.01,
      which is at the upper bound of those reported for typical Kerr medium. This
      stronger Kerr refractive index may be important for quantum-cascade lasers
      ultimately to demonstrate self-mode-locking.

PMID- 18711497
TI  - A novel, low-cost, high performance dissolved methane sensor for aqueous
      environments.
AB  - A new method for in-situ detection and measurement of dissolved methane in
      aqueous media/environments with a limit of detection of 0.2 nM (3 sigma, and t90
      approxiamtely 110s) and range (1-300 nM) is presented. The detection method is
      based on refractive index (RI) modulation of a modified PolyDiMethylSiloxane
      (PDMS) layer incorporating molecules of cryptophane-A [1] which have a selective
      and reversible affinity for methane [2]. The refractive index is accurately
      determined using surface plasmon resonance (SPR) [3]. A prototype sensor has been
      repeatedly tested, using a dissolved gas calibration system under a range of
      temperature and salinity regimes. Laboratory-based results show that the
      technique is specific, sensitive, and reversible. The method is suitable for
      miniaturization and incorporation into in situ sensor technology.

PMID- 18711498
TI  - Coherent energy exchange between components of a vector soliton in fiber lasers.
AB  - We report on the experimental evidence of four wave mixing (FWM) between the two
      polarization components of a vector soliton formed in a passively mode-locked
      fiber laser. Extra spectral sidebands with out-of-phase intensity variation
      between the polarization resolved soliton spectra was firstly observed, which was
      identified to be caused by the energy exchange between the two soliton
      polarization components. Other features of the FWM spectral sidebands and the
      soliton internal FWM were also experimentally investigated and numerically
      confirmed.

PMID- 18711499
TI  - Long-term carrier-envelope-phase stabilization of a femtosecond laser by the
      direct locking method.
AB  - We have developed a practical solution to implement the direct locking method for
      the carrier-envelope phase (CEP) stabilization of femtosecond laser pulses and
      achieved 24-hour CEP stabilization without realignment of any optical components.
      The direct locking method realizes the CEP stabilization in the time domain by
      directly quenching the beat signal from an f-to-2f interferometer and, thereby,
      locking every pulse to a same CEP. We have accomplished the long-term CEP
      stabilization using commercially available standard feedback electronics, and
      maintained the CEP stabilization with low jitter without using any frequency
      analyzing components, greatly facilitating the accessibility of the CEP
      stabilization.

PMID- 18711500
TI  - Weak-microcavity organic light-emitting diodes with improved light out-coupling.
AB  - We propose and demonstrate weak-microcavity organic light-emitting diode (OLED)
      displays with improved light-extraction and viewing-angle characteristics. A
      single pair of low- and high-index layers is inserted between indium tin oxide
      (ITO) and a glass substrate. The electroluminescent (EL) efficiencies of discrete
      red, green, and blue weak-microcavity OLEDs are enhanced by 56%, 107%, and 26%,
      respectively, with improved color purity. Moreover, full-color passive-matrix
      bottom-emitting OLED displays are fabricated by employing low-index layers of two
      thicknesses. As a display, the EL efficiency of white color was 27% higher than
      that of a conventional OLED display.

PMID- 18711501
TI  - Two-photon fluorescence correlation spectroscopy through a dual-clad optical
      fiber.
AB  - We report on the utilization of a dual-clad optical fiber for two-photon excited
      fluorescence correlation spectroscopy (FCS). High excitation efficiency is
      obtained by sending prechirped ultrafast pulses through the single-mode core of
      the fiber, while the fluorescence collection efficiency is enhanced because of
      the larger numerical aperture of the inner cladding. We show that the utilization
      of a dual-clad fiber is critical for ultrasensitive two-photon fluorescence
      detection. Our system has the ability to detect fluorescent nanospheres as small
      as 12 nm in radius. Quantum dots of radius 7 nm are also measured and show
      excellent signal to noise ratio. The particle sizes obtained from the fiber FCS
      system were confirmed by measurements using a commercial dynamic light scattering
      (DLS) system.

PMID- 18711502
TI  - Chirp effect in hard X-ray generation from liquid target when irradiated by
      femtosecond pulses.
AB  - The chirp effect on a X-ray emission intensity from a CsCl aqueous solution jet
      irradiated by femtosecond pulses was systematically studied. The p-polarized
      chirped pulses were more efficient as compared with the shortest pulses
      determined by the spectral bandwidth. The negatively-chirped pulses of
      approximately 240 fs duration produced up to 10 times larger X-ray intensity as
      compared with the transform-limited 160 fs pulses. The angular dependence of X
      ray generation can be explained by the resonant absorption. Numerical simulations
      of electron density evolution due to the avalanche and multi-photon absorption
      supports qualitatively well the experimental observations.

PMID- 18711503
TI  - Dynamics of pump-induced refractive index changes in single-mode Yb-doped optical
      fibers.
AB  - We quantify the refractive index changes (RIC) in single-mode ytterbium-doped
      optical fibers induced by optical pulses at 980 nm and, for the first time,
      report details of the effect dynamics. The RIC dynamics is shown to follow that
      of the population of the excited/unexcited ion states with a factor proportional
      to their polarizability difference (PD). The absolute PD value is evaluated in
      the spectral range of 1460-1620 nm for different fiber samples and is found to be
      independent on the fiber geometry and on the ion concentration. The PD dispersion
      profile indicates to a predominant far-resonance UV rather than near-resonant IR
      transitions contribution to the RIC.

PMID- 18711504
TI  - Compact polymeric four-wavelength multiplexers based on cascaded step-size MMI
      for 1G/10G hybrid TDM-PON applications.
AB  - A novel polymeric four-wavelength multiplexer based on a new design concept of
      cascaded step-size multimode interferometer (CSS-MMI) is first presented. It can
      be fabricated by using planar lightwave circuit (PLC) technology and is highly
      compatible with both current 1-Gbps and future 10Gbps optical transceivers for
      applications in next generation 1-Gbps and 10-Gbps coexisting time-division
      multiplexed passive optical network (TDM PON). By combining two types of proposed
      CSS-MMI 1??2 wavelength splitters, a compact 1.5cm-long four wavelength
      multiplexer is realized without requiring complicated design and tedious
      calculation. In addition, the upstream wavelength channel at 1310 nm has 0.18 dB
      low insertion loss and three downstream wavelength channels at 1490 nm, 1550 nm
      and 1590 nm exhibit insertion losses of 1.21 dB, 1.34 dB and 1.02 dB,
      respectively, with their extinction ratios ranging from 11.71 dB to 32.07 dB.

PMID- 18711505
TI  - Light-controllable photoresponsive liquid-crystal photonic crystal fiber.
AB  - We have developed all-optical modulation of photonic crystal fiber (PCF) by
      infiltrating photoresponsive liquid crystal (LC) into the voids within the
      cladding structure. The photo-induced phase transformation of the photoresponsive
      LC modulates the effective refractive index of the photoresponsive LC-filled
      cladding, thereby creating an environment of modifiable total internal reflection
      that tunes the output intensity of guided light upon the stimulus of optical
      field. The modulation range for the 632 nm wavelength is 10 dB and the response
      time for switching is less than 1 second by manually obstructing the pumping
      light path. In addition to altering the power of the pumping laser to actively
      tune the output intensity, the polarization direction of the pumping laser can
      also tune the output intensity by 5 dB.

PMID- 18711506
TI  - Vertical coupling between gap plasmon waveguides.
AB  - This work examines vertical coupling between gap plasmon waveguides for use in
      high confinement power transfer and power splitting applications at 1.55 microm
      free space wavelength. The supermode interference method is used to obtain key
      coupler performance parameters such as coupling length, extinction ratio, net
      coupled output power, radiated power, and reflected power as a function of
      waveguide center-to-center spacing, core refractive index, and gap width. The
      initial power distribution among the two coupler supermodes is obtained via the
      mode matching method for a single input waveguide feed. Excellent agreement with
      three-dimensional finite difference time domain simulations is observed for the
      case of square 50 nm gaps with core refractive indices of 2.50 and a center-to
      center spacing of 112 nm. Local maxima in the net coupled output power are found
      to coincide with local minima in the coupling length. An increase in the core
      refractive index from 1.00 to 2.5 increases the local maximum net coupled output
      power from 6.4% to 49% but decreases the extinction ratio from 12.7 to 6.94. A
      sweep of the width of the core from 25 to 100 nm increases the net coupled output
      power from 43.7% to 52.0%, but increases the coupling length from 1.58 to 3.19
      ???m and decreases the extinction ratio from 7.39 to 6.57.

PMID- 18711507
TI  - High quality quasi-Bessel beam generated by round-tip axicon.
AB  - We study theoretically and experimentally the spatial intensity distribution of
      the zero-order Bessel beam formed by the axicon which possess a rounded tip. Such
      a tip generates a refracted beam that interferes with the quasi-Bessel beam
      created behind the axicon. In turn an undesired intensity modulation occurs that
      significantly disturbs the unique properties of the quasi-Bessel beam--namely the
      constant shape of the lateral intensity distribution and the slow variation of
      the on-axis beam intensity along the beam propagation. We show how the spatial
      filtration of the beam in the Fourier plane improves this spatial beam
      distribution and removes the undesired modulation. We use an efficient numerical
      method based on Hankel transformations to simulate the propagation of the beam
      behind the axicon and filter. We experimentally measure the intensity
      distribution of the beam in many lateral planes and subsequently reconstruct the
      spatial intensity distribution of the beam. Computed and measured beam
      distributions are compared and the obtained agreement is very good.

PMID- 18711508
TI  - Sub-Poissonian shot noise of a high internal gain injection photon detector.
AB  - The noise performance of an infrared injection photon detector with very high
      internal gain was investigated at a wavelength of 1.55 mum. The devices showed
      sub-Poissonian shot noise with Fano factors around 0.55 at 0.7 V at room
      temperature. Optical to electrical conversion factors of 3000 electrons per
      absorbed photon were recorded at 0.7 V. The change in noise-equivalent power with
      respect to bias voltage was evaluated. The optical to electrical conversion
      factor and Fano factor were measured under increasing illumination and compared
      to theoretical expectations.

PMID- 18711509
TI  - Kaleidoscope modes in large aperture Porro prism resonators.
AB  - We apply a new method of modeling Porro prism resonators, using the concept of
      rotating loss screens, to study stable and unstable Porro prism resonator. We
      show that the previously observed petal--like modal output is in fact only the
      lowest order mode, and reveal that a variety of kaleidoscope beam modes will be
      produced by these resonators when the intra--cavity apertures are sufficiently
      large to allow higher order modes to oscillate. We also show that only stable
      resonators will produce these modes.

PMID- 18711510
TI  - Formation of superhydrophobic poly(dimethysiloxane) by ultrafast laser-induced
      surface modification.
AB  - The formation of hemispherical nanostructures and microscaled papilla by
      ultrafast laser irradiation was found to be a potential method to generate
      superhydrophbic surface of synthetic polymers. Irradiation of femtosecond laser
      creates roughened poly(dimethylsiloxane) (PDMS) surface in nano- and microscales,
      of which topography fairly well imitate a Lotus leaf in nature. The modified
      surface showed superhydrophobicity with a contact angle higher than 170 degrees
      as well as sliding angle less than 3 degrees. We further demonstrated that
      negative replica of the processed PDMS surface exhibit large contact angle
      hysteresis with a sliding angle of 90 degrees while the positive replica
      maintains superhydrophobicity.

PMID- 18711511
TI  - Intrinsic Raman spectroscopy for quantitative biological spectroscopy part I:
      theory and simulations.
AB  - We present a novel technique, intrinsic Raman spectroscopy (IRS), to correct
      turbidity-induced Raman spectral distortions, resulting in the intrinsic Raman
      spectrum that would be observed in the absence of scattering and absorption. We
      develop an expression relating the observed and intrinsic Raman spectra through
      diffuse reflectance using the photon migration depiction of light transport.
      Numerical simulations are employed to validate the theoretical results and study
      the dependence of this expression on sample size and elastic scattering
      anisotropy.

PMID- 18711512
TI  - Intrinsic Raman spectroscopy for quantitative biological spectroscopy part II:
      experimental applications.
AB  - We demonstrate the effectiveness of intrinsic Raman spectroscopy (IRS) at
      reducing errors caused by absorption and scattering. Physical tissue models,
      solutions of varying absorption and scattering coefficients with known
      concentrations of Raman scatterers, are studied. We show significant improvement
      in prediction error by implementing IRS to predict concentrations of Raman
      scatterers using both ordinary least squares regression (OLS) and partial least
      squares regression (PLS). In particular, we show that IRS provides a robust
      calibration model that does not increase in error when applied to samples with
      optical properties outside the range of calibration.

PMID- 18711513
TI  - In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive
      optics scanning laser ophthalmoscopy.
AB  - In vivo measurement of retinal blood flow is obtained by measuring the blood
      velocity of erythrocytes and lumen diameters of the blood vessels using an
      adaptive optics scanning laser ophthalmoscope. Erythrocyte velocity is measured
      by tracking erythrocytes moving across a horizontal scanning line. This approach
      provides high temporal bandwidth measurements, allowing the fluctuation of blood
      flow during cardiac cycles to be measured. The technique is most applicable to
      medium-sized blood vessels.

PMID- 18711514
TI  - Fabrication of large-area patterned porous silicon distributed Bragg reflectors.
AB  - A process to fabricate porous silicon Bragg reflectors patterned on a micrometer
      lateral scale over wafer areas of several square centimeters is described. This
      process is based on a new type of projection system involving a megavolt
      accelerator and a quadrupole lens system to project a uniform distribution of MeV
      ions over a wafer surface, which is coated with a multilevel mask. In conjunction
      with electrochemical anodisation, this enables the rapid production of high
      density arrays of a variety of optical and photonic components in silicon such as
      waveguides and optical microcavities for applications in high-definition
      reflective displays and optical communications.

PMID- 18711515
TI  - A highly symmetric two-handed metamaterial spontaneously matching the wave
      impedance.
AB  - We demonstrate a two-handed metamaterial (THM), composed of highly symmetric
      three-layered structures operated at normal incidence. Not only does the THM
      exhibit two distinct allowed bands with right-handed and left-handed
      electromagnetic responses, but posses a further advantage of being independent to
      the polarizations of external excitations. In addition, the THM automatically
      matches the wave impedance in free space, leading to maximum transmittances about
      0.8 dB in the left-handed band and almost 0 dB in the right-handed band,
      respectively. Such a THM can be employed for diverse electromagnetic devices
      including dual-band bandpass filters, ultra-wide bandpass filters and
      superlenses.

PMID- 18711516
TI  - Electrically pumped single-photon emission in the visible spectral range up to 80
      K.
AB  - We present an electrically pumped single-photon emitter in the visible spectral
      range, working up to 80 K, realized using a self-assembled single InP quantum
      dot. We confirm that the electroluminescense is emitted from a single quantum dot
      by performing second-order autocorrelation measurements and show that the
      deviation from perfect single-photon emission is entirely related to detector
      limitations and background signal. Emission from both neutral and charged exciton
      complexes was observed with their relative intensites depending on the injection
      current and temperature.

PMID- 18711517
TI  - Carbon nanotube doped liquid crystal OCB cells: physical and electro-optical
      properties.
AB  - We report single-wall carbon nanotube (CNT) doped liquid crystal materials which
      show significant improvement in the response time for optical controlled
      birefringence (OCB) cells. Four different types of liquid crystals (LCs) were
      chosen to mix with CNTs and they demonstrated similar results in improving the
      response time. Experimental results show that the anchoring energy at alignment
      layers has been changed by CNT doping. CNTs were attracted to the alignment layer
      and modified the property of the surface. The anchoring enhancement is due to the
      pi-pi electron stacking between the CNTs, LC molecules and alignment layers.

PMID- 18711518
TI  - Shaping ultrafast laser inscribed optical waveguides using a deformable mirror.
AB  - We use a two-dimensional deformable mirror to shape the spatial profile of an
      ultrafast laser beam that is then used to inscribe structures in a soda-lime
      silica glass slide. By doing so we demonstrate that it is possible to control the
      asymmetry of the cross section of ultrafast laser inscribed optical waveguides
      via the curvature of the deformable mirror. When tested using 1.55 mum light, the
      optimum waveguide exhibited coupling losses of approximately 0.2 dB/facet to
      Corning SMF-28 single mode fiber and propagation losses of approximately 1.5
      dB.cm(-1). This technique promises the possibility of combining rapid processing
      speeds with the ability to vary the waveguide cross section along its length.

PMID- 18711519
TI  - Quasi-near field terahertz generation and detection.
AB  - We describe a simple terahertz (THz) time domain spectrometer with a bandwidth
      extending up to 7.5 THz. We show that by keeping the generation and detection
      crystals close to each other a high signal-to-noise ratio (SNR) can be achieved
      without using lock-in detection and dry nitrogen flushing. The observed spectra
      show very good agreement with the spectra calculated based on a simple model
      which includes phase matching and absorption in the generation and detection
      crystals. Using this set-up we have measured the absorption lines in D-tartaric
      acid from 0.5 THz up to 7 THz. We show that the high frequency region > 3 THz is
      the better choice to measure small changes in the water content of a hygroscopic
      sample compared to the low frequency region.

PMID- 18711520
TI  - Synthesis design of artificial magnetic metamaterials using a genetic algorithm.
AB  - In this article, we present a genetic algorithm (GA) as one branch of artificial
      intelligence (AI) for the optimization-design of the artificial magnetic
      metamaterial whose structure is automatically generated by computer through the
      filling element methodology. A representative design example, metamaterials with
      permeability of negative unity, is investigated and the optimized structures
      found by the GA are presented. It is also demonstrated that our approach is
      effective for the synthesis of functional magnetic and electric metamaterials
      with optimal structures. This GA-based optimization-design technique shows great
      versatility and applicability in the design of functional metamaterials.

PMID- 18711521
TI  - Rapid simulation of wide-angle scattering from mitochondria in single cells.
AB  - It has been shown that the mitochondria are the dominant source of large-angle
      light scattering from human cells. In the limit of small mitochondria, we show
      that the large-angle (isotropic) light scattering of mitochondria may be analyzed
      and simulated with an adaptation of classical X-ray diffraction theory. In
      addition, we show that this approach may be extended to the case of anisotropic
      scatter. These results enable the rapid simulation and analysis of mitochondrial
      scattering patterns and allow the determination of some aspects of cell structure
      directly from experimental scattering patterns.

PMID- 18711522
TI  - The mechanism of rare earth incorporation in solution doping process.
AB  - The mechanism involved during solution doping process has been systematically
      investigated by correlating the soot characteristics and solution parameters with
      the amount of rare earth (RE) incorporated in the core of optical fiber.
      Experiments show that the amount of RE incorporation may be controlled with
      better precision by adjusting Al ion concentration in the soaking solution. A
      model has been developed on the basis of cooperative adsorption mechanism
      correlating different parameters in the overall process. Theoretical estimation
      shows good agreement with the experimental results and can be used to predict the
      extent of RE incorporation for any composition if the soot layer characteristics
      are known.

PMID- 18711523
TI  - Analog differential-phase detection in optical coherence reflectometer.
AB  - A novel differential-phase optical coherence reflectometer (DP-OCR) was proposed
      using a low-coherence source, integrating it with an analog differential-phase
      decoding method. In the experiment, the DP-OCR performed a localized surface
      profile measurement of an optical grating (1200 lp/mm) and demonstrated its
      ability to measure the translation speed of a tilted mirror. Experimentally, the
      resolution of the axial displacement of proposed DP-OCR at 185 pm was
      demonstrated.

PMID- 18711524
TI  - Generation and detection of broadband coherent terahertz radiation using 17-fs
      ultrashort pulse fiber laser.
AB  - We describe the generation and detection of broadband terahertz radiation using
      an all-fiber laser. Optical pulses from a mode-locked fiber laser oscillator are
      compressed using nonlinear and dispersion effects induced in optical fibers, and
      17-fs optical pulses with 170-kW peak power are generated at the wavelength
      region around 1.5 microm. By injecting these pulses into an organic crystal DAST
      (4-N, N-dimethylamino-4'-N"-methyl-stilbazolium tosylate), broadband terahertz
      field is radiated at 0.1-25 THz. The frequency region exceeding 20 THz is
      achieved with a fiber laser for the first time.

PMID- 18711525
TI  - Observation of accelerating parabolic beams.
AB  - We report the first observation of accelerating parabolic beams. These
      accelerating parabolic beams are similar to the Airy beams because they exhibit
      the unusual ability to remain diffraction-free while having a quadratic
      transverse shift during propagation. The amplitude and phase masks required to
      generate these beams are encoded onto a single liquid crystal display.
      Experimental results agree well with theory.

PMID- 18711526
TI  - Surface inspection by monitoring spectral shifts of localized plasmon resonances.
AB  - We present a numerical study of the spectral variations of localized surface
      plasmon resonances (LSPR) in a 3D-probe metallic nanoparticle scanned over an
      inhomoegeneous dielectric surface. The possibilities for both, index monitoring
      and lateral resolution at nanoscale level are explored, with special attention
      paid to the shape of the probe and the profile of the near field underneath.

PMID- 18711527
TI  - Self-healing properties of optical Airy beams.
AB  - We investigate both theoretically and experimentally the self-healing properties
      of accelerating Airy beams. We show that this class of waves tends to reform
      during propagation in spite of the severity of the imposed perturbations. In all
      occasions the reconstruction of these beams is interpreted through their internal
      transverse power flow. The robustness of these optical beams in scattering and
      turbulent environments is also studied experimentally. Our observations are in
      excellent agreement with numerical simulations.

PMID- 18711528
TI  - Analytical fitting model for rough-surface BRDF.
AB  - A physics-based model is developed for rough surface BRDF, taking into account
      angles of incidence and scattering, effective index, surface autocovariance, and
      correlation length. Shadowing is introduced on surface correlation length and
      reflectance. Separate terms are included for surface scatter, bulk scatter and
      retroreflection. Using the FindFit function in Mathematica, the functional form
      is fitted to BRDF measurements over a wide range of incident angles. The model
      has fourteen fitting parameters; once these are fixed, the model accurately
      describes scattering data over two orders of magnitude in BRDF without further
      adjustment. The resulting analytical model is convenient for numerical
      computations.

PMID- 18711529
TI  - Fabrication of photonic crystals with functional defects by one-step holographic
      lithography.
AB  - A one-step introduction of functional defects into a photonic crystal is
      demonstrated. By using a multi-beam phase-controlled holographic lithography,
      line-defects in a Bragg structure and embedded waveguides in a two-dimensional
      photonic crystal are fabricated. Intrinsic defect introduction into a 3
      dimensional photonic crystal is also proposed. This technique gives rise to a
      substantial reduction of the fabrication complexity and a significant improvement
      on the accuracy of the functional defects in photonic crystals.

PMID- 18711530
TI  - Investigation of the variations in the water leaving polarized reflectance from
      the POLDER satellite data over two biogeochemical contrasted oceanic areas.
AB  - The biogeochemical characterization of marine particles suspended in sea water,
      is of fundamental importance in many areas of ocean science. Previous studies
      based on theoretical calculations and field measurements have demonstrated the
      importance of the use of the polarized light field in the retrieval of the
      suspended marine particles properties. However, because of the weakness of the
      water leaving polarized signal and of the limited number of appropriate spatial
      sensors, such measurements have never been exploited from space. Here we show
      that the marine polarized remote sensing reflectance, as detected from the
      POLarization and Directionality of the Earth's Reflectances (POLDER) sensor, can
      be measured from space over bright waters and in absence of aerosols. This
      feasibility study is carried out over two oceanic areas characterized by
      different nature of the bulk particulate assemblage: the Barents sea during an
      intense coccolithophore bloom, and the Rio de la Plata estuary waters dominated
      by suspended sediments. The retrieved absolute values of the degree of
      polarization, P, its angular pattern, and its behavior with the scattering level
      are consistent with theory and field measurements. Radiative transfer simulations
      confirm the sensitivity of the POLDER-2 P values to the nature of the particulate
      assemblage. These preliminary results are very promising for the assessment of
      the bulk particle composition from remote sensing of the polarized signal, at
      least over highly scattering waters.

PMID- 18711531
TI  - Long-haul 10 Gbit/s linear and non-linear IMDD transmission over uncompensated
      standard fiber using a SQRT-metric MLSE receiver.
AB  - We experimentally demonstrated Intensity-Modulated Direct-Detection (IMDD) single
      channel 1,040 km linear transmission and 800 km non-linear transmission at 10
      Gb/s over standard single-mode (G.652) fiber, without any optical dispersion
      compensation or mitigation, using a Maximum-Likelihood Sequence-Estimation (MLSE)
      receiver employing the square-root (SQRT) branch metric with off-line processing.
      These experiments were designed as to probe the limits of the MLSE approach. They
      successfully showed that long-haul uncompensated transmission is in principle
      possible with MLSE, even in the presence of large uncompensated dispersion and
      strong intra-channel fiber non-linearities, provided that enough complexity can
      be built into the receiver. In the linear 1,040 km experiment, a Bit Error Rate
      (BER) of 10(-3) was achieved with an Optical Signal-to-Noise Ratio (OSNR) penalty
      with respect to back-to-back of 2.9 dB, using two samples per bit and 16,384
      trellis states. Several other set-ups were tested as well, including the use of
      only one sample per bit and fewer trellis states. In the non-linear 800 km
      experiment, power was ramped up to 12 dBm, exciting substantial Kerr non
      linearity, whose induced spectral-broadening exacerbated the effects of the large
      uncompensated dispersion of the link. Using an MLSE receiver with 1,024 states,
      we demonstrated a non-linear threshold of 9 dBm. We benchmarked this experiment
      towards simulations addressing various electrical and optical dispersion
      compensation strategies. We also carried out an analysis of error run-lengths, on
      both experiments, which showed that error burstiness may change considerably
      depending on the number of processor states, OSNR and the amount of non-linearity
      in the link.

PMID- 18711532
TI  - A staggered differential phase-shift keying modulation format for 100Gbit/s
      applications.
AB  - We propose and demonstrate by numerical simulation a new phase modulation format,
      the staggered differential phase-shift keying (SDPSK), for 100 Gbit/s
      applications. Non-return-to-zero (NRZ) SDPSK signals was generated by using two
      phase modulators, and return-to-zero (RZ) SDPSK signals with 50% duty cycle was
      generated by cascading a dual-arm Mach-Zehnder modulator. The demodulation of 2
      bit/symbol can be simply achieved on 1 bit rate through only one Mach-Zehnder
      delay interferometer and a balanced receiver. By comparing the transmission
      characteristics of the two staggered phase modulation formats with those of NRZ
      DPSK, RZ-DPSK, NRZ-DQPSK, and RZ-DQPSK, respectively, we show that, the SDPSK
      signal has similar chromatic dispersion and polarization-mode-dispersion
      tolerance to the DPSK signal with same NRZ or RZ shape, while the SDPSK signal
      has stronger nonlinear tolerance than the DPSK or DQPSK signal. In addition, the
      SDPSK signal has the best transmission performance when each signal was
      transmitted over 106km optical SMF+DCF, and then launched into a third-order
      Gaussian optical bandpass filter placed with beyond 125GHz bandwidth.

PMID- 18711533
TI  - Image analysis algorithms for cell contour recognition in budding yeast.
AB  - Quantification of protein abundance and subcellular localization dynamics from
      fluorescence microscopy images is of high contemporary interest in cell and
      molecular biology. For large-scale studies of cell populations and for time-lapse
      studies, such quantitative analysis can not be performed effectively without some
      kind of automated image analysis tool. Here, we present fast algorithms for
      automatic cell contour recognition in bright field images, optimized to the model
      organism budding yeast (Saccharomyces cerevisiae). The cell contours can be used
      to effectively quantify cell morphology parameters as well as protein abundance
      and subcellular localization from overlaid fluorescence data.

PMID- 18711534
TI  - Freeform LED lens for uniform illumination.
AB  - Light flux from LED must be redistributed to meet the needs of lighting in most
      cases, a new method is proposed for its secondary optic design. Based on
      refractive equation and energy conservation, a set of first-order partial
      differential equations which represent the characters of LED source and desired
      illumination were presented. The freeform lens was constructed by solving these
      equations numerically. The numerical results showed that we can get a freeform
      lens for the illumination of uniformity near to 90%, with considerable high
      computation speed. This method can shorten the designing time of the freeform
      lens with high accepted tolerance.

PMID- 18711535
TI  - Special optical fiber for temperature sensing based on cladding-mode resonance.
AB  - A fiber-optic temperature sensor by using a multi-cladding special fiber is
      presented. It works on the basis of leaky mode resonance from fiber core to outer
      cladding. With the thin-thickness inner cladding, the cladding mode is strongly
      excited and the resonant spectrum is very sensitive to the refractive index
      variation of coating material. By coating the special fiber with temperature
      sensitive silicone, the temperature response was investigated experimentally from
      -20 degrees C to 80 degrees C. The results show high temperature sensitivity (240
      pm/degrees C at 20 degrees C) and good repeatability.

PMID- 18711536
TI  - Photonic textiles for pulse oximetry.
AB  - Biomedical sensors, integrated into textiles would enable monitoring of many
      vitally important physiological parameters during our daily life. In this paper
      we demonstrate the design and performance of a textile based pulse oximeter,
      operating on the forefinger tip in transmission mode. The sensors consisted of
      plastic optical fibers integrated into common fabrics. To emit light to the human
      tissue and to collect transmitted light the fibers were either integrated into a
      textile substrate by embroidery (producing microbends with a nominal diameter of
      0.5 to 2 mm) or the fibers inside woven patterns have been altered mechanically
      after fabric production. In our experiments we used a two-wavelength approach
      (690 and 830 nm) for pulse wave acquisition and arterial oxygen saturation
      calculation. We have fabricated different specimens to study signal yield and
      quality, and a cotton glove, equipped with textile based light emitter and
      detector, has been used to examine movement artifacts. Our results show that
      textile-based oximetry is feasible with sufficient data quality and its potential
      as a wearable health monitoring device is promising.

PMID- 18711537
TI  - Thermal and Kerr nonlinear properties of plasma-deposited silicon nitride/
      silicon dioxide waveguides.
AB  - We introduce and present experimental evaluations of loss and nonlinear optical
      response in a waveguide and an optical resonator, both implemented with a silicon
      nitride/ silicon dioxide material platform prepared by plasma-enhanced chemical
      vapor deposition with dual frequency reactors that significantly reduce the
      stress and the consequent loss of the devices. We measure a relatively small loss
      of approximately 4dB/cm in the waveguides. The fabricated ring resonators in add
      drop and all-pass arrangements demonstrate quality factors of Q=12,900 and
      35,600. The resonators are used to measure both the thermal and ultrafast Kerr
      nonlinearities. The measured thermal nonlinearity is larger than expected, which
      is attributed to slower heat dissipation in the plasma-deposited silicon dioxide
      film. The n2 for silicon nitride that is unknown in the literature is measured,
      for the first time, as 2.4 x 10(-15)cm(2)/W, which is 10 times larger than that
      for silicon dioxide.

PMID- 18711538
TI  - Depth of field extension with spherical optics.
AB  - The introduction of spherical aberration in a lens design can be used to extend
      the depth of field while preserving resolution up to half the maximum diffraction
      limited spatial frequency. Two low-power microscope objectives are shown that
      achieve an extension of +/- 0.88 lambda in terms of wavefront error, which is
      shown to be comparable to alternative techniques but without the use of special
      phase elements. The lens performance is azimuth-independent and achromatic over
      the visible range.

PMID- 18711539
TI  - Constructing 3D crystal templates for photonic band gap materials using
      holographic optical tweezers.
AB  - A simple and robust method is presented for the construction of 3-dimensional
      crystals from silica and polystyrene microspheres. The crystals are suitable for
      use as templates in the production of three-dimensional photonic band gap (PBG)
      materials. Manipulation of the microspheres was achieved using a dynamic
      holographic assembler (DHA) consisting of computer controlled holographic optical
      tweezers. Attachment of the microspheres was achieved by adjusting their
      colloidal interactions during assembly. The method is demonstrated by
      constructing a variety of 3-dimensional crystals using spheres ranging in size
      from 3 microm down to 800 nm. A major advantage of the technique is that it may
      be used to build structures that cannot be made using self-assembly. This is
      illustrated through the construction of crystals in which line defects have been
      deliberately included, and by building simple cubic structures.

PMID- 18711540
TI  - Local electric field enhancement and polarization effects in a surface-enhanced
      Raman scattering fiber sensor with chessboard nanostructure.
AB  - A surface-enhanced Raman scattering fiber sensor with chessboard nanostructure on
      a cleaved fiber facet is studied by finite-difference time-domain method. Surface
      plasmons at the metal coated nanostructured fiber facet can be effectively
      excited and strong local electric field enhancement is obtained. Studies on the
      influence of light polarization demonstrate a large polarization dependence of
      the field enhancement factor while the polarization effects on the plasmon
      resonance wavelength are relatively small.

PMID- 18711541
TI  - Enhancing alignment tolerance of silicon waveguide by using a wide grating
      coupler.
AB  - We fabricate a 20 um wide grating coupler for a single-mode thermally-expanded
      core (TEC) fiber, in order to enhance positional tolerance in alignment. The
      minimal coupling loss is measured at 5 dB per facet and the optical 3 dB
      bandwidth is measured at 40 nm. The 3 dB alignment tolerance is measured at +-7.5
      microm in horizontal direction and +290 microm in vertical direction. The 1 dB
      alignment tolerance is measured at +-4.2 microm in horizontal direction and +125
      microm in vertical direction. The alignment tolerance is enhanced twice in
      horizontal direction and four times in vertical direction, compared with the
      coupling of a standard single-mode fiber to a standard 10 microm wide grating
      coupler which is also fabricated in this experiment.

PMID- 18711542
TI  - Polarization-sensitive optical coherence tomography based on polarization
      maintaining fibers and frequency multiplexing.
AB  - We report a novel polarization-maintaining fiber based optical coherence
      tomography for single detector imaging of tissue reflectivity and birefringence.
      A single depth scan yields quantitative birefringence information along the A
      line accurately. Since the orthogonal polarization channels are frequency
      multiplexed, the polarization information is extracted by using digital band-pass
      filters. Here, we introduce the optical system and present the reflectivity and
      birefringence images of biological tissues with an axial resolution of 7.9 microm
      and SNR of 30 dB.

PMID- 18711543
TI  - Twist effect on spectral properties of two-mode fiber acousto-optic filters.
AB  - The splitting and the shift of resonance peaks in the output spectrum of two-mode
      fiber acousto-optic devices caused by twist perturbation are described. An
      elliptical-core two-mode fiber and a two-mode photonic-crystal fiber are used for
      the analysis. The splitting of the resonance peaks are found to be almost
      linearly proportional to the twist angle of the fiber with the slopes of about
      0.58 nm/(rad/m) for the elliptical-core fiber and about 0.29 nm/(rad/m) for the
      photonic crystal fiber. The experimental results compare well with the
      theoretical predictions.

PMID- 18711544
TI  - Terahertz spectrum analyzer based on a terahertz frequency comb.
AB  - Precision frequency measurements of terahertz (THz) waves are required to
      establish metrology in the THz spectral region. However, frequency measurement
      techniques in this region are immature. We propose a THz spectrum analyzer to
      measure the absolute frequency and spectral shape of continuous-wave THz waves.
      Based on a stable frequency comb generated in a photoconductive antenna, the
      absolute frequency of a sub- THz test source was determined at a precision of 2.8
      x 10(-11). Furthermore, the spectral bandwidth of the THz spectrum analyzer can
      be extended over 1 THz, as demonstrated by measurement of a THz test source. This
      spectrum analyzer has the potential to become a powerful tool for THz frequency
      metrology.

PMID- 18711545
TI  - A single-shot imaging magnetometer using cold atoms.
AB  - We demonstrate a technique for imaging magnetic fields using velocity-selective
      two-photon resonances in a cold atom cloud. Freely expanding (85)Rb atoms
      released from a magneto-optical trap are exposed to a brief (approximately 1 ms),
      off-resonant, retro-reflected laser pulse in a lin-perp-lin configuration. Two
      photon resonance between magnetic sublevels occurs only for atoms in narrow
      velocity classes dependent on the magnetic field strength. The momentum of
      resonant atoms is altered by the pulse, and this two-photon momentum change is
      easily visible after further ballistic expansion. When the momentum pulse is
      applied to an atom cloud with finite size, magnetic field variations across the
      sample result in position-dependent features in images of the expanded cloud. We
      demonstrate the technique by imaging magnetic field variations over approximately
      5 mm with approximately 250 microm spatial resolution.

PMID- 18711546
TI  - Surface plasmon coupling in periodic metallic nanoparticle structures: a semi
      analytical model.
AB  - We report a semi-analytical model for calculating the coupling effects between
      the dipolar surface plasmon nanoparticles of a periodic structure. This model
      involves real-valued frequencies only and is therefore applicable to periodic
      structures with arbitrary dipolar units and environments.

PMID- 18711547
TI  - Three-dimensional visualization of objects in scattering medium by use of
      computational integral imaging.
AB  - In this paper, we propose a method to three-dimensionally visualize objects in a
      scattering medium using integral imaging. Our approach is based on a particular
      use of the interference phenomenon between the ballistic photons getting through
      the scattering medium and the scattered photons being scattered by the medium.
      For three-dimensional (3D) sensing of the scattered objects, the synthetic
      aperture integral imaging system under coherent illumination records the
      scattered elemental images of the objects. Then, the computational geometrical
      ray propagation algorithm is applied to the scattered elemental images in order
      to eliminate the interference patterns between scattered and object beams. The
      original 3D information of the scattered objects is recovered by multiple imaging
      channels, each with a unique perspective of the object. We present both
      simulation and experimental results with virtual and real objects to demonstrate
      the proposed concepts.

PMID- 18711548
TI  - Controlling uncoupled resonances in photonic crystals through breaking the mirror
      symmetry.
AB  - We show that modes in a photonic crystal slab that are uncoupled to outside
      radiation in a symmetric structure can be excited by breaking the mirror symmetry
      through introducing a protrusion on the side of the photonic crystal holes. We
      show that coupling to these resonances can be controlled by the strength of this
      asymmetry, and that it is also possible to choose among modes to couple to,
      through the shape of the asymmetry introduced. We provide simple theoretical
      arguments that explain the effect, and present eigenmode simulations and time
      domain simulations. We confirm this predicted behavior with measurements on a
      photonic crystal with a broken mirror symmetry that exhibits an additional sharp
      resonant feature with a linewidth of 0.5 nm, in agreement with both calculated
      and simulated predictions.

PMID- 18711549
TI  - A self-normalized, full time-resolved method for fluorescence diffuse optical
      tomography.
AB  - A full time-resolved scheme that has been previously applied in diffuse optical
      tomography is extended to time-domain fluorescence diffuse optical tomography
      regime, based on a finite-element-finite-time-difference photon diffusion
      modeling and a Newton-Raphson inversion framework. The merits of using full time
      resolved data are twofold: it helps evaluate the intrinsic performance of time
      domain mode for improvement of image quality and set up a valuable reference to
      the assessment of computationally efficient featured-data-based algorithms, and
      provides a self-normalized implementation to preclude the necessity of the
      scaling-factor calibration and spectroscopic-feature assessments of the system as
      well as to overcome the adversity of system instability. We validate the proposed
      methodology using simulated data, and evaluate its performances of simultaneous
      recovery of the fluorescent yield and lifetime as well as its superiority to the
      featured-data one in the fidelity of image reconstruction.

PMID- 18711550
TI  - Gain and noise characteristics of high-bit-rate silicon parametric amplifiers.
AB  - We report a numerical investigation on parametric amplification of high-bit-rate
      signals and related noise figure inside silicon waveguides in the presence of two
      photon absorption (TPA), TPA-induced free-carrier absorption, free-carrier
      induced dispersion and linear loss. Different pump parameters are considered to
      achieve net gain and low noise figure. We show that the net gain can only be
      achieved in the anomalous dispersion regime at the high-repetition-rate, if short
      pulses are used. An evaluation of noise properties of parametric amplification in
      silicon waveguides is presented. By choosing pulsed pump in suitably designed
      silicon waveguides, parametric amplification can be a chip-scale solution in the
      high-speed optical communication and optical signal processing systems.

PMID- 18711551
TI  - Chip-to-chip optical interconnect using gold long-range surface plasmon polariton
      waveguides.
AB  - We demonstrate a novel on-board chip-to-chip optical interconnect using long
      range surface plasmon polariton (LR-SPP) waveguides that feature 2.5-cm-long gold
      strips embedded in a low loss polymer cladding. A TM-mode vertical-cavity surface
      emitting laser (VCSEL) operating at a wavelength of 1.3 microm was butt-coupled
      into the waveguides in order to excite a fundamental LR-SPP mode and then the
      transmitted light was received with a photo-diode (PD). The waveguide width is
      varied in the range of 1.5-5.0 microm in order to optimize the insertion loss
      where the 3-microm-wide waveguide provides a minimum insertion loss of -17 dB,
      consisting of 6 dB/cm propagation loss and 2 dB coupling loss. An interconnect
      system based on the optimized waveguide with a 4-channel array is assembled with
      the arrayed optoelectronic chips. It shows the feasibility of 10 Gbps (2.5 Gbps x
      4 channels) signal transmission indicating that the LR-SPP waveguide is a
      potential transmission line for optical interconnection.

PMID- 18711552
TI  - Correction of sampling errors due to laser tuning rate fluctuations in swept
      wavelength interferometry.
AB  - The frequency-sampling method is widely used to accommodate nonlinear laser
      tuning in swept-wavelength interferometric techniques such as optical frequency
      domain reflectometry (OFDR) and swept-wavelength optical coherence tomography
      (OCT). In this paper we analyze the frequency-sampling method and identify two
      sources of sampling errors. One source of error is the limit of an underlying
      approximation for long interferometer path mismatches and fast laser tuning
      rates. A second source of error is transmission delays in data acquisition
      hardware. We show that the measurement system can be configured such that the two
      error sources cancel to second order. We present experimental verification of
      sampling error correction using a general swept-wavelength interferometer with a
      significantly nonlinear laser sweep.

PMID- 18711553
TI  - Micro objective lens with NA 0.65 for the blue-light small-form-factor optical
      pickup head.
AB  - A micro objective lens with the numerical aperture (NA) of 0.65 and clear
      aperture of 1.1mm was designed, fabricated, and tested for the proposed blue
      light small-form-factor optical pickup head system. It adopted the finite optical
      conjugation and could be produced by using the glass molding technique. The
      experimental results verify the optical performance near the diffraction-limited
      focus spot for the applications of high-density portable optical storage systems.

PMID- 18711554
TI  - Loss determination in microsphere resonators by phase-shift cavity ring-down
      measurements.
AB  - The optical loss of whispering gallery modes of resonantly excited microresonator
      spheres is determined by optical lifetime measurements. The phase-shift cavity
      ring-down technique is used to extract ring-down times and optical loss from the
      difference in amplitude modulation phase between the light entering the
      microresonator and light scattered from the microresonator. In addition, the
      phase lag of the light exiting the waveguide, which was used to couple light into
      the resonator, was measured. The intensity and phase measurements were fully
      described by a model that assumed interference of the cavity modes with the light
      propagating in the waveguide.

PMID- 18711555
TI  - Liquid crystal modulator with ultra-wide dynamic range and adjustable driving
      voltage.
AB  - We demonstrated a reflective-type liquid crystal (LC) intensity modulator in 1550
      nm telecomm band. An effective way to compensate the residual phase of a LC cell
      is proposed. With the adjustment of a true zero-order quarter wave plate and
      enhanced by total internal reflection induced birefringence, over 53 dB dynamic
      range was achieved, which is much desired for some high-end optical
      communication, infrared scene projection applications. In addition, the driving
      voltages were decreased and adjustable. Mechanical and spectral tolerance
      measurements show that our LC modulator is quite stable. Further applications of
      our experimental setup were discussed including bio-sensors and high speed
      modulators.

PMID- 18711556
TI  - Meshed index profile method for photonic crystal fibers with arbitrary
      structures.
AB  - A meshed index profile method, which is based on the localized function method,
      is demonstrated for analyzing modal characteristics of photonic crystal fibers
      with arbitrary air-hole structures. The index profile of PCF, which is expressed
      as a sum of meshed unit matrix, is substituted to full wave equation. By solving
      this full wave equation, we obtain the modal characteristics of the PCF such as
      the mode field distribution, the birefringence and the waveguide dispersion. The
      accuracy of the proposed meshed index profile method (MIPM) is demonstrated by
      examining the effective index and the birefringence of the two degenerate
      fundamental modes in the PCF with a triangular air-hole lattice. The MIPM is not
      restricted to the PCF structure and will be useful in designing various PCF
      devices.

PMID- 18711557
TI  - Monte Carlo algorithm for efficient simulation of time-resolved fluorescence in
      layered turbid media.
AB  - We present an efficient Monte Carlo algorithm for simulation of time-resolved
      fluorescence in a layered turbid medium. It is based on the propagation of
      excitation and fluorescence photon bundles and the assumption of equal reduced
      scattering coefficients at the excitation and emission wavelengths. In addition
      to distributions of times of arrival of fluorescence photons at the detector, 3-D
      spatial generation probabilities were calculated. The algorithm was validated by
      comparison with the analytical solution of the diffusion equation for time
      resolved fluorescence from a homogeneous semi-infinite turbid medium. It was
      applied to a two-layered model mimicking intra- and extracerebral compartments of
      the adult human head.

PMID- 18711558
TI  - A note on plane wave diffraction by a perfectly conducting strip in a homogeneous
      bi-isotropic medium.
AB  - We studied the problem of diffraction of an electromagnetic plane wave by a
      perfectly conducting finite strip in a homogeneous bi-isotropic medium and
      obtained some improved results which were presented both mathematically and
      graphically. The problem was solved by using the Wiener-Hopf technique and
      Fourier transform. The scattered field in the far zone was determined by the
      method of steepest decent. The significance of present analysis was that it
      recovered the results when a strip was widened into a half plane.

PMID- 18711559
TI  - Whispering-gallery modes and light emission from a Si-nanocrystal-based single
      microdisk resonator.
AB  - We report on visible light emission from Si-nanocrystal based optically active
      microdisk resonators. The room temperature photoluminescence (PL) from single
      microdisks shows the characteristic modal structure of whispering-gallery modes.
      The emission is both TE and TM-polarized in 300 nm thick microdisks, while
      thinner ones (135 nm) support only TE-like modes. Thinner disks have the
      advantage to filter out higher order radial mode families, allowing for measuring
      only the most intense first order modal structure. We reveal subnanometer
      linewidths and corresponding quality factors as high as 2800, limited by the
      spectral resolution of the experimental setup. Moreover, we observe a
      modification of mode linewidth by a factor 13 as a function of pump power. The
      origin of this effect is attributed to an excited carrier absorption loss
      mechanism.

PMID- 18711560
TI  - Finding the field transfer matrix of scattering media.
AB  - When illuminated by temporally coherent light, multiply scattering media produce
      speckle patterns that in many situations are unpolarized on spatial averaging. As
      a result, the underlying field statistics are assumed to be Gaussian and
      information about them can be extracted from intensity-intensity correlations.
      However, such an approach cannot be applied to any scattering medium where the
      interaction leads to partially developed speckle patterns. We present a general
      procedure to directly measure the field transfer matrix of a linear medium
      without regard to the scattering regime. Experimental results demonstrate the
      ability of our procedure to correctly measure field transfer matrices and use
      them to recover the polarization state of incident illumination.

PMID- 18711561
TI  - Pseudo-random single photon counting for time-resolved optical measurement.
AB  - We report a new time-resolved optical measurement method which combines single
      photon counting and the spread spectrum time-resolved optical measurement method.
      A laser diode modulated with pseudo-random bit sequences replaces the short pulse
      laser used in conventional time-resolved optical systems, while a single photon
      detector records the pulse sequence in response to the modulated excitation.
      Periodic cross-correlation is used to retrieve the impulse response. Feasibility
      of our approach is validated experimentally. A rise time around 150 picoseconds
      has been achieved with our prototype. Besides high temporal resolution, the new
      method also affords other benefits such as high photon counting rate, fast data
      acquisition, portability, and low cost.

PMID- 18711562
TI  - Analysis of the scalability of diffraction-limited fiber lasers and amplifiers to
      high average power.
AB  - We analyze the scalability of diffraction-limited fiber lasers considering
      thermal, non-linear, damage and pump coupling limits as well as fiber mode field
      diameter (MFD) restrictions. We derive new general relationships based upon
      practical considerations. Our analysis shows that if the fiber's MFD could be
      increased arbitrarily, 36 kW of power could be obtained with diffraction-limited
      quality from a fiber laser or amplifier. This power limit is determined by
      thermal and non-linear limits that combine to prevent further power scaling,
      irrespective of increases in mode size. However, limits to the scaling of the MFD
      may restrict fiber lasers to lower output powers.

PMID- 18711563
TI  - Optical frequency combs generated by four-wave mixing in optical fibers for
      astrophysical spectrometer calibration and metrology.
AB  - Optical frequency combs generated by multiple four-wave mixing in short and
      highly nonlinear optical fibers are proposed for use as high precision frequency
      markers, calibration of astrophysical spectrometers, broadband spectroscopy and
      metrology. Implementations can involve two optical frequency standards as input
      lasers, or one standard and a second laser phase-locked to it using a stable
      microwave reference oscillator. Energy and momentum conservation required by the
      parametric generation assures phase coherence among comb frequencies, while
      fibers with short lengths can avoid linewidth broadening and stimulated Brillouin
      scattering. In contrast to combs from mode-locked lasers or microcavities, the
      absence of a resonator allows large tuning of the frequency spacing from tens of
      gigahertz to beyond teraHertz.

PMID- 18711564
TI  - Optically compensated circular polarizers for liquid crystal displays.
AB  - An optical compensation principle of the crossed circular polarizers is developed
      to widen the viewing angle of high-transmittance multi-domain vertical-alignment
      liquid crystal displays (MVA-LCDs). The optical properties of a biaxial film are
      analyzed by the Berreman 4x4 matrix method, and the analytical solution for the
      slow-axis orientation of a biaxial film is calculated to obtain the compensation
      principle of the crossed circular polarizers. Based on this compensation
      principle, the high-transmittance MVA-LCD theoretically has a complete 80 degrees
      viewing cone for contrast ratio (CR)>100:1 and experimental results reveal that
      the compensated high-transmittance MVA-LCD can achieve a viewing angle of over
      the entire 80 degrees viewing cone for CR>20:1. Practical application as a mobile
      display is emphasized.

PMID- 18711565
TI  - Electric and magnetic resonances in arrays of coupled gold nanoparticle in-tandem
      pairs.
AB  - We present an experimental and theoretical study on the optical properties of
      arrays of gold nanoparticle in-tandem pairs (nanosandwiches). The well-ordered Au
      pairs with diameters down to 35 nm and separation distances down to 10 nm were
      fabricated using extreme ultraviolet (EUV) interference lithography. The strong
      near-field coupling of the nanoparticles leads to electric and magnetic
      resonances, which can be well reproduced by Finite-Difference Time-Domain (FDTD)
      calculations. The influence of the structural parameters, such as nanoparticle
      diameter and separation distance, on the hybridized modes is investigated. The
      energy and lifetimes of these modes are studied, providing valuable physical
      insight for the design of novel plasmonic structures and metamaterials.

PMID- 18711566
TI  - Continuously phase-matched terahertz difference frequency generation in an
      embedded-waveguide structure supporting only fundamental modes.
AB  - We demonstrate an all-single mode structure which enables continuous phase
      matching of difference frequency generated THz light from the near-IR. This
      structure provides a long interaction length by way of well-confined collinear
      propagation of pumps and product without diffraction, resulting in high
      conversion efficiency. A LiNbO(3) version of this structure achieved a power
      normalized conversion efficiency of 1.3 x 10(-7) W(-1)--some 23 times larger than
      the largest previously reported results.

PMID- 18711567
TI  - Interferometric microring-resonant 2 x 2 optical switches.
AB  - We present modeling and simulation results on a new family of waveguided
      interferometric 2 x 2 optical routing switches actuated by electro-optic or
      thermo-optic or all-optical control. Two pairs of coupled microring resonators
      provide two 3dB coupling regions within a compact Mach-Zehnder geometry. An index
      perturbation (delta)n of 2 x 10(-3) is sufficient to produce 100% 2 x 2
      switching. This perturbation can be applied to one arm of the MZI or to the four
      rings in the device or to an additional ring that is coupled to one arm. We find
      that push-pull control is effective for switching: for example, when carriers are
      injected in one region and depleted in a corresponding second region. An optical
      transfer-matrix technique is employed to determine the electromagnetic response
      (the 1550-nm switching characteristics) of the three device-types. Microdisks can
      be employed instead of microrings, if desired.

PMID- 18711568
TI  - Nonlinear immunofluorescent assay for androgenic hormones based on resonant
      structures.
AB  - We report for the first time the use of two photon fluorescence as detection
      method of affinity binding reactions. We use a resonant grating waveguide
      structure as platform enhancement for detecting the interaction between
      fluorescent labeled Boldenone, a non-natural androgenic hormone, and a specific
      anti-anabolic antibody. We were able to detect a surface coverage of
      approximately 0.7 ng/mm(2).

PMID- 18711569
TI  - Simulations of the nonlinear Helmholtz equation: arrest of beam collapse,
      nonparaxial solitons and counter-propagating beams.
AB  - We solve the (2+1)D nonlinear Helmholtz equation (NLH) for input beams that
      collapse in the simpler NLS model. Thereby, we provide the first ever numerical
      evidence that nonparaxiality and backscattering can arrest the collapse. We also
      solve the (1+1)D NLH and show that solitons with radius of only half the
      wavelength can propagate over forty diffraction lengths with no distortions. In
      both cases we calculate the backscattered field, which has not been done
      previously. Finally, we compute the dynamics of counter-propagating solitons
      using the NLH model, which is more comprehensive than the previously used coupled
      NLS model.

PMID- 18711570
TI  - An attenuation-partition based iterative phase retrieval algorithm for in-line
      phase-contrast imaging.
AB  - For medical applications of the in-line phase-contrast x-ray imaging, phase
      retrieval is a crucial step for quantitative imaging such as reconstructing the 3
      D distribution of tissue linear attenuation coefficients and refraction indices.
      The conventional phase retrieval algorithms, such as the transport of intensity
      equation (TIE) based algorithms, are not robust against the quantum noise that
      appears in acquired images due to the radiation dose constraints in medical
      imaging. In this work a new attenuation-partition based iterative phase retrieval
      algorithm is proposed. This new algorithm takes advantage of the correlation
      between the attenuation and phase-shift, and is much robust against noise in
      acquired images. Phase retrieval results from experimental images show that this
      new iterative algorithm is fast and robust, and it has good potential for medical
      x-ray imaging applications.

PMID- 18711571
TI  - Coupled-ring-resonator-based silicon modulator for enhanced performance.
AB  - A compact silicon coupled-ring modulator structure is proposed. Two rings are
      coupled to each other, and only one of these rings is actively driven and over
      coupled to a waveguide, which enables high modulation speed. The resultant notch
      filter profile is steeper than that of the single ring and has exhibited a
      smaller resonance shift and lower driving electrical power. Simulation results
      include: (i) potentially 60-Gb/s non-return-to-zero (NRZ) data modulation and
      over 20-dB extinction ratio can be achieved by shifting the active ring by a 20
      GHz resonance shift, (ii) the frequency chirp of the modulated signals can be
      adjusted by varying the coupling coefficient between the two rings, and (iii)
      dispersion tolerance at 0.5-dB power penalty is extended from 18 to 85 ps/nm, for
      a 40-Gb/s NRZ signal.

PMID- 18711572
TI  - Fast detection of humidity with a subwavelength-diameter fiber taper coated with
      gelatin film.
AB  - A subwavelength-diameter tapered optical fiber coated with gelatin layer for fast
      relative humidity (RH) sensing is reported. The sensing element is composed of a
      680-nm-diameter fiber taper coated with a 80-nm-thickness 8-mm-length gelatin
      layer, and is operated at a wavelength of 1550 nm. When exposed to moisture, the
      change in refractive index of the gelatin layer changes the mode field of the
      guided mode of the coated fiber, and converts a portion of power from guided mode
      to radiation mode, resulting in RH-dependent loss for optical sensing. The sensor
      is operated within a wide humidity range (9-94% RH) with high sensitivity and
      good reversibility. Measured response time is about 70 ms, which is one or two
      orders of magnitude faster than other types of RH sensors relying on conventional
      optical fibers or films.

PMID- 18711573
TI  - Excitation of s-polarized surface electromagnetic waves in inhomogeneous
      dielectric media.
AB  - We consider a model of an inhomogeneous dielectric slab first studied by
      Shvartzburg, Petite and Auby [J. Opt. Soc. Am. B 16, 966 (1999)] and several
      variations of that model and study the excitation of s-polarized surface
      electromagnetic waves on the surface of inhomogeneous dielectric media. Using the
      invariant imbedding theory of wave propagation in stratified media, we calculate
      the reflectance and the absorptance of an s wave incident obliquely on a
      dielectric slab in the Otto configuration, as a function of incident angle and
      frequency. We also calculate the spatial distribution of the electric field
      intensity in the inhomogeneous region. We find that in all cases we have
      considered, s-polarized surface waves are excited at certain incident angles and
      frequencies. We discuss the physical mechanism of the surface wave generation and
      the possibility of experimental observations of these effects.

PMID- 18711574
TI  - Extension ratio of depth of field by wavefront coding method.
AB  - An analysis of the depth of field (DOF) of the wavefront coding imaging system
      with a cubic phase mask is presented. A necessary condition on the base of that
      MTF of wavefront coding system is defocus-independent is described. Then the
      extension ratio of the DOF relative to that of traditional optical system is
      calculated. And the conclusion is also verified by the simulation results.

PMID- 18711575
TI  - Pointing and tracking errors due to localized deformation in inter-satellite
      laser communication links.
AB  - Instead of Zernike polynomials, ellipse Gaussian model is proposed to represent
      localized wave-front deformation in researching pointing and tracking errors in
      inter-satellite laser communication links, which can simplify the calculation. It
      is shown that both pointing and tracking errors depend on the center deepness h,
      the radiuses a and b, and the distance d of the Gaussian distortion and change
      regularly as they increase. The maximum peak values of pointing and tracking
      errors always appear around h=0.2lambda. The influence of localized deformation
      is up to 0.7microrad for pointing error, and 0.5microrad for tracking error. To
      reduce the impact of localized deformation on pointing and tracking errors, the
      machining precision of optical devices, which should be more greater than 0.2?,
      is proposed. The principle of choosing the optical devices with localized
      deformation is presented, and the method that adjusts the pointing direction to
      compensate pointing and tracking errors is given. We hope the results can be used
      in the design of inter-satellite lasercom systems.

PMID- 18711576
TI  - Fluorescence correlation spectroscopy in a reverse Kretchmann surface plasmon
      assisted microscope.
AB  - Fluorescence Correlation Spectroscopy (FCS) demands a high rate of photon
      detection per molecule, low background, and large fluctuations of fluorescence
      associated with translational motion. The new approach presented here, Surface
      Plasmon Assisted Microscope (SPAM), meets these requirements by drastically
      limiting the observation volume. In this method, the observational layer is made
      so thin that fluctuations are mostly due to the axial motion of molecules. This
      is conveniently realized by placing a sample on a thin metal film and
      illuminating it with a laser beam through an aqueous medium. The excited
      fluorophores close to the surface couple (via near-field interactions) to surface
      plasmons in the metal. Propagated surface plasmons decouple on opposite side of
      the metal film as a far-field radiation and emit in directional manner.
      Fluorescence is collected with a high Numerical Aperture objective. A confocal
      aperture inserted in its conjugate image plane reduces lateral dimensions of the
      detection volume to a diffraction limit. The thickness of the detection layer is
      reduced further by metal quenching of excited fluorophores at a close proximity
      (about 30 nm) to the surface. We used a suspension of fluorescent microspheres to
      show that FCS-SPAM is an efficient method to measure molecular diffusion.

PMID- 18711577
TI  - Quantum efficiency enhancement in film by making nanoparticles of polyfluorene.
AB  - We report on conjugated polymer nanoparticles of polyfluorene that were formed to
      exhibit higher fluorescence quantum efficiency in film (68%) and reduce undesired
      emission peak wavelength shifts in film (by 20 nm), compared to the solid-state
      polymer thin film made directly out of the same polymer solution without forming
      nanoparticles. Using the facile reprecipitation method, solutions of poly[9,9
      dihexyl-9H-fluorene] in THF were added at different volume ratios to obtain
      different size distributions of nanoparticle dispersions in water. This allowed
      us to control the sizedependent optical emission of our polyfluorene
      nanoparticles. Such organic nanoparticles hold great promise for use as efficient
      emitters in optoelectronic device applications.

PMID- 18711578
TI  - Measurement of PMD tolerance in 40-Gb/s polarization-multiplexed RZ-DQPSK.
AB  - We experimentally investigate the first-order polarization-mode dispersion (PMD)
      tolerance of two polarization-multiplexed (POLMUX) RZ-DQPSK signals at overall 40
      Gb/s. The polarization demultiplexing is enabled by an automatic endless
      polarization stabilizer. Time-interleaving the two orthogonally polarized RZ
      DQPSK signals minimizes the crosstalk due to the non-ideal polarization
      stabilization, while it represents the worstcase for the PMD-induced crosstalk.
      Bit-error rate measurements are performed both in back-to-back and after 25-km
      standard single-mode fiber. The PMD tolerance is evaluated as a function of the
      instantaneous differential group delay, introduced by a first-order PMD emulator.
      40-Gb/s POLMUX RZ-DQPSK is more sensitive to PMD than single-polarization 20-Gb/s
      DQPSK, while it is more PMD-tolerant than 40-Gb/s NRZ-OOK. Besides, its chromatic
      dispersion robustness is similar to the single-polarization 20-Gb/s DQPSK. The
      combination of POLMUX and DQPSK is therefore very promising in view of
      transmission systems at high bit-rate.

PMID- 18711580
TI  - Two-dimensional electromagnetic cloaks with arbitrary geometries.
AB  - Transformation optics opens an exciting gateway to design electromagnetic
      "invisibility" cloaks with anisotropic and inhomogeneous medium. In this paper,
      we establish a generalized transformation procedure to highly improve the
      flexibilities for the design of two-dimensional (2D) cloaks. The general
      expressions for the complex medium parameters are developed, which can be readily
      applied to design 2D cloaks with arbitrary geometries. An example of 2D cloak
      with irregular cross section is designed and studied by full-wave simulations.
      The Huygens' Principle is applied to quantitatively evaluate its unusual
      electromagnetic behaviors. All the theoretical and numerical results verify the
      effectiveness of the proposed approach. The generalization in this Paper makes a
      great step forward for the flexible design of electromagnetic cloaks with
      arbitrary shapes.

PMID- 18711579
TI  - DWDM channel spacing tunable optical TDM carrier from a mode-locked weak-resonant
      cavity Fabry-Perot laser diode based fiber ring.
AB  - A novel optical TDM pulsed carrier with tunable mode spacing matching the ITU-T
      defined DWDM channels is demonstrated, which is generated from an optically
      injection-mode-locked weak-resonant-cavity Fabry-Perot laser diode (FPLD) with
      10%-end-facet reflectivity. The FPLD exhibits relatively weak cavity modes and a
      gain spectral linewidth covering >33.5 nm. The least common multiple of the mode
      spacing determined by both the weak-resonant-cavity FPLD and the fiber-ring
      cavity can be tunable by adjusting length of the fiber ring cavity or the FPLD
      temperature to approach the desired 200GHz DWDM channel spacing of 1.6 nm. At a
      specific fiber-ring cavity length, such a least-common- multiple selection rule
      results in 12 lasing modes between 1532 and 1545 nm naturally and a mode-locking
      pulsewidth of 19 ps broadened by group velocity dispersion among different modes.
      With an additional intracavity bandpass filter, the operating wavelength can
      further extend from 1520 to 1553.5 nm. After channel filtering, each selected
      longitudinal mode gives rise to a shortened pulsewidth of 12 ps due to the
      reduced group velocity dispersion. By linear dispersion compensating with a 55-m
      long dispersion compensation fiber (DCF), the pulsewidth can be further
      compressed to 8 ps with its corresponding peak-to-peak chirp reducing from 9.7 to
      4.3 GHz.

PMID- 18711581
TI  - Bandgap formation and selective suppression of Bloch states in birefringent
      gyrotropic Bragg waveguides.
AB  - Birefringent magnetophotonic crystals are found to exhibit degeneracy breaking
      for asymmetric contradirectional coupling in planar waveguides. Fundamental to
      high-order local normal mode coupling leads to partially overlapping gyrotropic
      bandgaps inside the Brillouin zone and partial suppression of Bloch mode
      propagation. A large magneto-optically active reorientation in polarization state
      is found for allowed Bloch modes at bandgap edges.

PMID- 18711583
TI  - High brightness, tunable biphoton source at 976 nm for quantum spectroscopy.
AB  - A compact all solid state continuous-wave biphoton source, tunable around 488 nm,
      for quantum spectroscopic applications based on a frequency doubled diode laser
      system is presented. Copolarized photon pairs in the fundamental transversal mode
      could be generated at 976 nm by spontaneous parametric down conversion inside a
      type-0 quasi phase matched periodically poled lithium niobate waveguide crystal
      with an efficiency of 8-10(-6). A high flux rate greater than 10(7) photon pairs
      per second has been achieved at pump powers in the muW range resulting in more
      than 7-10(9) photon pairs/s-mW. Further a detailed investigation of the spectral
      behavior and the flux rate as a function of the detuning from the degenerated
      case is presented.

PMID- 18711582
TI  - Direct amplification of terawatt sub-10-fs pulses in a CPA system of Ti:sapphire
      laser.
AB  - We have developed a chirped pulse amplification system of Ti:sapphire laser
      generating a 9.9 fs pulse with a pulse energy of 11 mJ at a repetition rate of 10
      Hz. Spectral narrowing during amplification is successfully compensated by using
      specially designed partial mirrors and broadband high-damage-threshold mirrors.
      This is the first demonstration, to the best of our knowledge, of the direct
      amplification of terawatt sub-10-fs pulses in a chirped pulse amplification
      system of Ti:sapphire laser.

PMID- 18711584
TI  - Evaluation of large girth LDPC codes for PMD compensation by turbo equalization.
AB  - Large-girth quasi-cyclic LDPC codes have been experimentally evaluated for use in
      PMD compensation by turbo equalization for a 10 Gb/s NRZ optical transmission
      system, and observing one sample per bit. Net effective coding gain improvement
      for girth-10, rate 0.906 code of length 11936 over maximum a posteriori
      probability (MAP) detector for differential group delay of 125 ps is 6.25 dB at
      BER of 10(-6). Girth-10 LDPC code of rate 0.8 outperforms the girth-10 code of
      rate 0.906 by 2.75 dB, and provides the net effective coding gain improvement of
      9 dB at the same BER. It is experimentally determined that girth-10 LDPC codes of
      length around 15000 approach channel capacity limit within 1.25 dB.

PMID- 18711585
TI  - A new scanning heterodyne interferometer scheme for mapping both surface
      structure and effective local reflection coefficient.
AB  - A new scanning microscope scheme which can map both phase and amplitude change of
      the probe beam is introduced. We will show that the true surface structure can be
      imaged by using the results of phase measurements while the amplitude image
      represents the map of the magnitude of the effective local reflection coefficient
      (ELRC). Relation between the surface structure and the ELRC is discussed. Spatial
      resolution is 0.67 microm which is limited by diffraction and the precision for
      measuring point-to-point variation of the average height of the surface structure
      is a few nanometers. Potential of this microscopy on surface diagnostics is
      discussed.

PMID- 18711586
TI  - Polarized photoluminescence from single GaN nanorods: effects of optical
      confinement.
AB  - By measuring linearly polarized photoluminescence (PL) from single, isolated
      gallium nitride (GaN) nanorods with the rod diameters in the subwavelength regime
      (30-90 nm), we present clear evidence for size dependence of polarization
      anisotropy. The maximum polarization ratio at room temperature (approximately 0.9
      with emission and excitation light polarized parallel to the long axis of
      nanorod) occurs at the rod diameter of approximately 40 nm. The experimental data
      are compared with the recent theoretical model proposed for thick semiconductor
      nanowires. It is concluded that the optical confinement effects in this size
      regime play an important role in the observed giant polarization anisotropy.
      Furthermore, we have performed a temperature-dependent study of polarized PL to
      show the importance of internal emission anisotropy at low temperatures.

PMID- 18711587
TI  - Theoretical and experimental study of optothermal expansion and optothermal
      microactuator.
AB  - A new type of microactuators based on optothermal (OT) expansion is introduced.
      The mechanism of the OT expansion is theoretically analyzed, and comprehensive
      models for OT expansion and bi-direction microactuator are presented in this
      paper. An expansion arm and a microswitch-like OT microactuator with 1200microm
      length are fabricated by an excimer laser micromachining system using single
      layer material. A laser diode (650nm) is employed as the external power source to
      activate the arm and the microactuator. Experimental results indicate that the OT
      expansion increment is approximately linear with the laser power irradiating the
      expansion arm, coinciding with theoretical predictions quite well. As to the
      switch-like microactuator, an enlarged bi-direction deflection has been obviously
      observed. The OT expansion and deflection amplitude that can reach micron scale
      is generally large enough for most microsystems. The new technique of OT
      microactuators can be widely applied in those fields where simple structure, easy
      fabrication, large displacement, wireless and remote controlling are required.

PMID- 18711588
TI  - Acquisition of gated spectra from a supercontinuum using ultrafast optical Kerr
      gate of lead phthalocyanine-doped hybrid glasses.
AB  - We demonstrated the selection of the chirped supercontinuum using an ultrafast
      optical Kerr gate (OKG) of lead phthalocyanine (PbPc)- doped hybrid glasses.
      Using the OKG, narrow bandwidth and symmetrical gated spectra were obtained
      continuously from the chirped supercontinuum generated in a sapphire plate with a
      femtosecond laser. Experimental results show that the obtained Kerr-gated spectra
      using the PbPc-glass have many advantages comparing with that using CS(2).

PMID- 18711608
TI  - Parallel import and pacemakers: who pays the ferryman?

PMID- 18711607
TI  - Case history: more than a beauty case!: A case for case histories.

PMID- 18711609
TI  - Aborted sudden cardiac death in a 52-yearold man without structural heart
      disease.
AB  - Sudden cardiac death in the absence of apparent structural heart disease is an
      uncommon phenomenon. The majority of these patients do not have 'normal' hearts
      and specific diagnostic tools are required to identify structural or functional
      abnormalities. We describe the history of a 50-yearold man who survived
      ventricular fibrillation. Clinical investigation, including a coronary
      angiography and electrophysiological study, appeared to be normal. An implantable
      cardioverter defibrillator was inserted. Follow-up Holter monitoring was
      performed after a recurrent episode of ventricular tachycardia. It demonstrated
      transient ST-segment elevation. An acetylcholine provocation test was
      subsequently carried out. Reversible coronary spasm of the left descending
      coronary artery was found, during which a diagonal branch was occluded. It may be
      concluded that coronary spasm provocation is of value in the routine diagnostic
      work-up of patients surviving sudden cardiac death without apparent heart
      disease. (Neth Heart J 2008;16:239-41.).

PMID- 18711610
TI  - Recurrence of cardiac arrest after 14 years without ICD interventions: a VF
      cluster immediately after delivery.
AB  - One day after childbirth, a 29-year-old woman had several episodes of polymorphic
      ventricular tachycardia and ventricular fibrillation. She was rescued by an
      internal cardioverter defibrillator (ICD) which she had received 14 years ago,
      after out-of-hospital cardiac arrest, without recurrences until now. The
      electrocardiogram showed a normal QT interval, and ventricular premature beats,
      which seemed to arise from the same site. This case report illustrates that, even
      after years with freedom of ICD therapy, depleted devices still have to be
      replaced. (Neth Heart J 2008;16:242-5.).

PMID- 18711611
TI  - Short-coupled variant of torsade de pointes.
AB  - A 36-year-old man with a history of primary sclerosing cholangitis and epilepsy
      was admitted to our hospital for cholangitis. During admission he was
      resuscitated because of ventricular fibrillation. ECGs showed multiple
      ventricular premature beats (VPBs) with a short coupling interval (240 ms),
      resulting in frequent torsade de pointes (TdP). In total, the patient had to be
      defibrillated 12 times. Short-coupled TdP is a rare variant of polymorphic
      ventricular tachycardia, with unknown aetiology. Verapamil seems to be the only
      drug able to suppress the arrhythmia. Verapamil, however, does not lower the risk
      of sudden death; therefore, an ICD implantation is advised. (Neth Heart J
      2008;16:246-9.).

PMID- 18711612
TI  - Pulmonary hypertension: the role of the electrocardiogram.
AB  - A 54-year-old female was referred to our centre for further evaluation of
      recently established severe pulmonary hypertension. Six months prior to
      presentation to the cardiologist of the referring centre, the patient had first
      experienced exertional dyspnoea. At the time of presentation to the referring
      cardiologist, the patient's ECG showed signs of an increased right heart load.
      Interestingly, this patient had undergone a thorough cardiac evaluation in the
      referring centre seven years before when she presented with severe
      hyperthyroidism. At that time there were no symptoms or signs of pulmonary
      hypertension on ECG, echocardiography, or at heart catheterisation. Thorough
      evaluation in cooperation with the referring centre demonstrated that this
      patient was suffering from idiopathic pulmonary arterial hypertension, a rare
      form of pulmonary hypertension. We conclude this report with a discussion on the
      potential use of the ECG for the diagnosis of increased right heart load. (Neth
      Heart J 2008;16:250-4.).

PMID- 18711613
TI  - Patent ductus arteriosus in adults: Case report and review illustrating the
      spectrum of the disease.
AB  - Patent ductus arteriosus (PDA) is a congenital heart defect in which the ductus
      arteriosus, a vascular structure between the pulmonary artery and the aorta that
      normally closes shortly after birth, remains open. We present two cases of adults
      with PDA. A 28-year-old lady had a small PDA without any symptoms or left heart
      overload. The PDA was closed for endocarditis prevention using a coil. In a 37
      year-old lady with palpitations, collapse, dyspnoea and left heart overload
      caused by a large PDA, percutaneous closure of the PDA was performed with an
      Amplatzer device. Transcatheter closure has been established to be the method of
      choice for treating a PDA in adults. (Neth Heart J 2008;16:255-9.).

PMID- 18711614
TI  - An unexpected finding late after repair of coarctation of the aorta.
AB  - We describe a late complication in a 75-year-old man 50 years after repair of a
      coarctation of the aorta (CoA). Two years after an aortic valve replacement,
      mitral valve repair and radiofrequency MAZE the patient presented with dyspnoea
      and right-sided heart failure, based on a large pseudoaneurysm of the descending
      aorta, compressing the main bronchus and possibly temporarily the pulmonary
      arterial system. After sealing the aneurysm with an endovascular stent the
      patient recovered uneventfully. Recommendations are made for follow-up in
      patients after repair of CoA. (Neth Heart J 2008;16:260-3.).

PMID- 18711615
TI  - Successful percutaneous balloon valvuloplasty in a preterm infant weighing 1500 g
      with critical pulmonary valve stenosis.
AB  - We describe a successful cardiac intervention in an infant, born at 32 weeks of
      gestation, with a birth weight of 1040 g, who had a critical pulmonary valve
      stenosis with the right ventricular pressure twice the systemic pressure.
      Continuous prostaglandin E infusion kept the arterial duct open and at the age of
      four weeks and a weight of 1500 g a balloon valvuloplasty was performed, which
      reduced the systolic right ventricular pressure to below the systemic pressure.
      Two weeks later the procedure was repeated because of increasing right
      ventricular pressure. At two months of age the mean systolic transpulmonary
      Doppler gradient was 30 mmHg with an adequate right ventricular volume. The
      neurological status of the infant was normal and the femoral vein was patent.
      Timely interventional heart catheterisation is a successful method of treatment
      in critical pulmonary valve stenosis in infants with a low birth weight. (Neth
      Heart J 2008;16:264-6.).

PMID- 18711616
TI  - R-on-T with massive ST-segment displacement unmasking dispersion of
      repolarisation associated with torsade de pointes.

PMID- 18711617
TI  - Atrial fibrillation: an unusual cause.

PMID- 18711618
TI  - Discovery of a persistent left superior vena cava during pacemaker implantation.

PMID- 18711619
TI  - High shear stress influences plaque vulnerability Part of the data presented in
      this paper were published in Stroke 2007;38:2379-81.
AB  - Shear stress of the blood at the vessel wall plays an important role in many
      processes in the cardiovascular system primarily focused on the regulation of
      vessel lumen and wall dimensions. There is ample evidence that atherosclerotic
      plaques are generated at low shear stress regions in the cardiovascular system,
      while high shear stress regions are protected. In the course of plaque
      progression, advanced plaques start to encroach into the lumen, and thereby start
      to experience high shear stress at the endothelium. Until now the consequences of
      high shear stress working at the endothelium of an advanced plaque are unknown.
      As high shear stress influences tissue regression, we hypothesised that high
      shear stress can destabilise the plaque by cap weakening leading to ulceration.
      We investigated this hypothesis in a magnetic resonance imaging (MRI) dataset of
      a 67-year-old woman with a plaque in the carotid artery at baseline and an ulcer
      at ten-month follow-up. The lumen, plaque components (lipid/necrotic core,
      intraplaque haemorrhage) and ulcer were reconstructed three dimensionally and the
      geometry at baseline was used for shear stress calculation using computational
      fluid dynamics. Correlation of the change in plaque composition with the shear
      stress at baseline showed that the ulcer was generated exclusively at the high
      shear stress location. In this serial MRI study we found plaque ulceration at the
      high shear stress location of a protruding plaque in the carotid artery. Our data
      suggest that high shear stress influences plaque vulnerability and therefore may
      become a potential parameter for predicting future events. (Neth Heart J
      2008;16:280-3.).

PMID- 18711620
TI  - Letter to the editor.

PMID- 18711621
TI  - Chylous peritonitis with small bowel obstruction.

PMID- 18711622
TI  - Familial erythrocytosis arising from a gain-of-function mutation in the HIF2A
      gene of the oxygen sensing pathway.
AB  - A mutation of HIF-2 alpha has been detected in three generations of a family with
      erythrocytosis and the mutation co-segregated with the erythrocytosis phenotype.
      Functional studies revealed that Gly537Trp mutation would significantly impair
      the function of HIF-2 alpha thus leading to increased synthesis of Epo. In
      addition to VHL and PHD2 a further member of the oxygen sensing pathway, namely
      HIF-2 alpha,can be a cause of erythrocytosis. Furthermore, HIF-2 alpha plays an
      important role in the regulation of Epo production. Continued study of idiopathic
      cases of erythrocytosis with raised serum Epo will reveal whether HIF-2 alpha
      will be a major cause of erythrocytosis on par with VHL.

PMID- 18711623
TI  - Giant cell tumour of the tendon sheath - an unusual cause for locking of the knee
      joint.

PMID- 18711624
TI  - Paratyphoid blamed on Ulster: a nursing odyssey.
AB  - SUMMARY: The aim of the Modicum mission from the United States was to determine
      the fate of the Western World, the Second Front and the Manhattan Project plans
      for development of atomic weapons. The Modicum mission was appointed in March
      1942 by Franklin Delano Roosevelt as President and Commander-in-Chief of the US
      forces. The journey via the Anglican Cathedral in Bermuda, to Gander, to London,
      to Ulster was eventful. There was a clay-pigeon shooting contest in Gander.
      Generals Marshall, Eisenhower, Clark and Averell Harriman were outshot by their
      pilot. In Ulster, an escorting US sergeant killed a Londonderry bus driver with
      three shots. At a house party requested by King George VI and General Marshall,
      at Ashbrook, Ardmore, near Londonderry, it is alleged Averell Harriman was
      poisoned with Salmonella schottmulleri. He was delirious and 'gravely ill' for
      three weeks at 3 Grosvenor Square next to the American Embassy. He subsequently
      married his "other nurse", Pamela. Ambassador Pamela Churchill Harriman, a long
      time ardent supporter of the Clintons, died in February 1997 following a stroke.

PMID- 18711625
TI  - Iatrogenic splenic injury in percutaneous procedures.

PMID- 18711626
TI  - The impact of long-term lithium treatment on renal function in an outpatient
      population.
AB  - AIM: This study aims to compare younger and older populations of lithium-treated
      patients and to examine the impact of long-term lithium treatment on renal
      function. METHODS: A retrospective, cross-sectional survey of all patients
      attending a specialist clinic was carried out. Demographic, clinical and
      biochemical data from the two groups were compared, and stepwise regression was
      used to investigate an association between duration of lithium treatment and
      renal function. RESULTS: The findings reveal a positive association between
      duration of lithium use and mean serum creatinine levels (t=3.369, p=0.001), and
      so prolonged lithium treatment may be a risk factor for progressive renal
      impairment. However, under appropriate supervision this may not be of clinical
      relevance. CONCLUSION: We conclude that lithium can be safely prescribed over a
      protracted period of time, even in elderly populations, but should be monitored
      closely under specialist supervision, to ensure early identification and
      management of adverse effects.

PMID- 18711627
TI  - Isolated mediastinal adenopathy: the case for mediastinoscopy.
AB  - BACKGROUND: We report our experience with mediastinoscopy at Auckland city
      hospital, a tertiary referral centre. We wished to examine correlations between
      clinical diagnosis and that made by histological sampling of enlarged mediastinal
      nodes particularly in patients with isolated mediastinal adenopathy. METHODS: We
      retrospectively reviewed clinical records of all patients who underwent
      mediastinoscopy in a five year period, mediastinoscopy was performed in the
      presence of enlarged lymph nodes (short axis > 1cm) found at CT. Mediastinoscopy
      was indicated for diagnostic staging of mediastinal adenopathy related to a
      parenchymal lung mass, diagnosis of isolated mediastinal adenopathy and diagnosis
      of mediastinal adenopathy with other CT findings. Data relating to indication,
      pre-test diagnosis, node stations sampled, histology, and operative complications
      were collected. RESULTS: Mediastinoscopy was performed in 137 consecutive
      patients. Seventy five patients had a lung mass, 47 had isolated mediastinal
      adenopathy and 15 had other CT findings. One operative complication occurred. In
      those patients with isolated adenopathy the following diagnoses were reached;
      sarcoidosis 23, TB 15, lymphoma 4, carcinoma 4, no diagnosis 1. Final diagnosis
      was significantly associated with patient's ethnicity. There was high sensitivity
      and specificity on comparison of clinical and histological diagnosis for both TB
      and sarcoidosis cases. CONCLUSIONS: Mediastinoscopy proved to be safe and
      effective in nodal assessment of the mediastinum. In carefully selected cases
      procedural morbidity and mortality may be avoided by application of features
      related to patient's ethnicity and radiological findings.

PMID- 18711629
TI  - Mesothelioma - "not just in the chest".

PMID- 18711628
TI  - Myocardial revascularization by off pump coronary bypass surgery (OPCABG): a ten
      year review.
AB  - BACKGROUND: The use of cardiopulmonary bypass (CPB) may contribute to post
      operative complications and organ dysfunction. Off pump coronary artery bypass
      grafting (OPCABG) avoids the use of CPB and hence is proposed to reduce these
      complications. We present the results of OPCABG in Northern Ireland over ten
      years. METHODS: Data was collected retrospectively from 1995 to 2005. Follow-up
      was done by telephonic questionnaire and from medical records within a closing
      interval of two months. RESULTS: 324 patients (224 male) underwent OPCABG with a
      median age of 62 years (range 35 to 79 years). There were 149 patients with CCS
      class III/IV angina and 48 with NYHA class III/IV. 148 patients had suffered a
      myocardial infarction in the past. 36 patients had a pre-operative predictive
      mortality score (EuroSCORE) of >5 and 48 patients had a preoperative LVEF of
      <30%. 585 bypass grafts were constructed (LAD=260, Diagonal=27, LCX/OM=123,
      RCA/PDA=103, RCA/PLV=72). Four patients needed to be converted from OPCABG to CPB
      on table. Another four patients needed re-operation due to graft related problems
      in the post-operative period and 6 needed post-operative Intra-aortic Balloon
      Pump (IABP) support. Post-operative complications included 3 TIAs, 1 complete
      stroke, 9 patients with renal failure and 51 patients developed atrial
      fibrillation post operatively. There was one peri-operative death due to
      pulmonary edema. Ninety percent of patients were in CCS angina class I/II and
      NYHA class I/II post-operatively. Forty one patients developed significant
      recurrence of angina requiring medical management, with 7 patients needing
      PCI/stenting. At the time of follow-up (median 5 years, range 3 months to 10
      years) 9 patients had died. CONCLUSIONS: Off pump coronary artery bypass (OPCABG)
      can be achieved with a low mortality and good medium to long term survival.
      OPCABG is associated with fewer post-op complications and comparable late
      coronary interventions.

PMID- 18711630
TI  - Minimally invasive parathyroid exploration for solitary adenoma. Initial
      experience with an open, 'short incision' approach.
AB  - BACKGROUND: In the vast majority of patients with primary hyperparathyroidism
      (HPT) the causative pathology is a benign solitary adenoma. The conventional
      surgical approach for HPT has involved bilateral cervical exploration with
      attempted identification of all four parathyroids and resection of enlarged
      glands. However, in recent years new techniques have permitted accurate
      preoperative localisation of the single parathyroid tumour in many patients. This
      has facilitated a focused unilateral operation to be performed in patients with a
      solitary parathyroid adenoma. More recently we have progressed to a minimally
      invasive surgical approach for such individuals in whom the tumour has been
      localised preoperatively. PATIENTS & METHODS: Between September 2004 and July
      2006, 24 patients with proven HPT, underwent focused, unilateral cervical
      exploration through a short (2.5-3 cm) incision placed low on the appropriate
      side of the neck. Preoperatively, each patient had been shown to have a single
      focus of activity after parathyroid isotope scanning. RESULTS: There were 21
      females and 3 males in the study group with a mean age of 61.5 years (range 25 -
      84 years) at the time of operation. The approach was successful in 22 patients
      with a mean operating time of 49 minutes (range 22-85 minutes). Postoperatively,
      the serum calcium level returned to normal in every patient and has remained so
      during a mean follow up period of 11.5 months (range 1-22 months). No individual
      developed postoperative hypocalcaemia although one patient developed a temporary
      unilateral vocal cord paralysis. CONCLUSION: A short incision cervical approach
      for HPT due to solitary adenoma is a viable alternative for appropriately
      selected patients.

PMID- 18711631
TI  - Predictors of excess mortality after myocardial infarction in women.
AB  - BACKGROUND: Research suggests that women have higher mortality after acute
      myocardial infarction (AMI) than men. Potential factors to explain this disparity
      include delay to presentation, less aggressive interventional strategies, and
      more severe disease at coronary angiography in women. METHODS: Consecutive
      patients (n=663) presenting to coronary care between Jan 2002 and Jan 2005 with
      ischemic type chest pain and AMI (troponin T >0.09ng/ml) were recruited. Details
      of the presentation and management were obtained from the medical notes. The
      primary endpoint was three month all cause mortality. RESULTS: Of these patients
      31% (205/663) were female. Mean age of women was 70 (SD 11) and 63 (SD 13) for
      men (p<0.001). There was no difference between the sexes for delay in
      presentation or treatment or for ST elevation infarction site. Women had prior
      hypertension more than men (49% 100/205 vs. 38% 174/458, p=0.008). Women were
      less likely to have diagnostic catheterisation (67% 137/205 vs. 80% 365/458
      p<0.001). Both genders had similar coronary artery disease extent and frequencies
      of LV impairment (EF<45%) and were equally likely to undergo revascularisation
      (79% 108/137 vs. 81% 295/365 p=NS). There was an excess 3 month mortality among
      women (11% 23/205 vs. 5% 24/458 in men p=0.006). INDEPENDENT: predictors of 3
      month mortality by logistic regression analysis were age (OR 1.06, 95% CI 1.03 
      1.09, p<0.001) and LV impairment (OR 0.28, 95% CI 0.13-0.56, p<0.001).
      CONCLUSION: As LV impairment was comparable in men and women, the excess
      mortality identified is due to older age at presentation of women.

PMID- 18711633
TI  - 40 years hard labour.

PMID- 18711632
TI  - Foreign body ingestion in prisoners - the Belfast experience.
AB  - Deliberate ingestion of foreign bodies is common amongst prison inmates. The
      motives behind the ingestion are variable. As the only designated hospital in
      Northern Ireland treating acute surgical pathologies in the prison population, we
      reviewed our experience of foreign body ingestion between March 1998 and June
      2007. Types of foreign objects, symptomatology, haematological analyses,
      radiological findings, operative intervention and complications were retrieved
      from case notes. A literature search was performed using Medline to correlate
      this clinical data with published evidence to produce therapeutic guidelines to
      assist the surgical multi-disciplinary team. Eleven prisoners presented with
      foreign body ingestion over the study period (M=8 and F=3, mean age: 28.1 years,
      range 21-48). Mean follow-up was 597 days (range 335-3325 days). Although the
      literature states that most foreign bodies usually pass spontaneously without the
      need for intervention, this study demonstrates a higher intervention rate of 36%
      within the Northern Irish prison population in comparison with other prisoners.

PMID- 18711634
TI  - Climate change and its impact on health.

PMID- 18711635
TI  - A classic diagnosis with a new 'spin'.
AB  - We describe a case of pericardial constriction following viral pericarditis and
      illustrate the use of cardiac magnetic resonance imaging in the diagnostic
      process. The advantages of cardiac magnetic resonance in the investigation of
      pericardial disease are briefly explained.

PMID- 18711636
TI  - Protein complex evolution does not involve extensive network rewiring.
AB  - The formation of proteins into stable protein complexes plays a fundamental role
      in the operation of the cell. The study of the degree of evolutionary
      conservation of protein complexes between species and the evolution of protein
      protein interactions has been hampered by lack of comprehensive coverage of the
      high-throughput (HTP) technologies that measure the interactome. We show that new
      high-throughput datasets on protein co-purification in yeast have a substantially
      lower false negative rate than previous datasets when compared to known
      complexes. These datasets are therefore more suitable to estimate the
      conservation of protein complex membership than hitherto possible. We perform
      comparative genomics between curated protein complexes from human and the HTP
      data in Saccharomyces cerevisiae to study the evolution of co-complex
      memberships. This analysis revealed that out of the 5,960 protein pairs that are
      part of the same complex in human, 2,216 are absent because both proteins lack an
      ortholog in S. cerevisiae, while for 1,828 the co-complex membership is disrupted
      because one of the two proteins lacks an ortholog. For the remaining 1,916
      protein pairs, only 10% were never co-purified in the large-scale experiments.
      This implies a conservation level of co-complex membership of 90% when the genes
      coding for the protein pairs that participate in the same protein complex are
      also conserved. We conclude that the evolutionary dynamics of protein complexes
      are, by and large, not the result of network rewiring (i.e. acquisition or loss
      of co-complex memberships), but mainly due to genomic acquisition or loss of
      genes coding for subunits. We thus reveal evidence for the tight interrelation of
      genomic and network evolution.

PMID- 18711637
TI  - The spatiotemporal pattern of Src activation at lipid rafts revealed by diffusion
      corrected FRET imaging.
AB  - Genetically encoded biosensors based on fluorescence resonance energy transfer
      (FRET) have been widely applied to visualize the molecular activity in live cells
      with high spatiotemporal resolution. However, the rapid diffusion of biosensor
      proteins hinders a precise reconstruction of the actual molecular activation map.
      Based on fluorescence recovery after photobleaching (FRAP) experiments, we have
      developed a finite element (FE) method to analyze, simulate, and subtract the
      diffusion effect of mobile biosensors. This method has been applied to analyze
      the mobility of Src FRET biosensors engineered to reside at different
      subcompartments in live cells. The results indicate that the Src biosensor
      located in the cytoplasm moves 4-8 folds faster (0.93+/-0.06 microm(2)/sec) than
      those anchored on different compartments in plasma membrane (at lipid raft:
      0.11+/-0.01 microm(2)/sec and outside: 0.18+/-0.02 microm(2)/sec). The mobility
      of biosensor at lipid rafts is slower than that outside of lipid rafts and is
      dominated by two-dimensional diffusion. When this diffusion effect was subtracted
      from the FRET ratio images, high Src activity at lipid rafts was observed at
      clustered regions proximal to the cell periphery, which remained relatively
      stationary upon epidermal growth factor (EGF) stimulation. This result suggests
      that EGF induced a Src activation at lipid rafts with well-coordinated
      spatiotemporal patterns. Our FE-based method also provides an integrated platform
      of image analysis for studying molecular mobility and reconstructing the
      spatiotemporal activation maps of signaling molecules in live cells.

PMID- 18711638
TI  - Using expression profiles of Caenorhabditis elegans neurons to identify genes
      that mediate synaptic connectivity.
AB  - Synaptic wiring of neurons in Caenorhabditis elegans is largely invariable
      between animals. It has been suggested that this feature stems from genetically
      encoded molecular markers that guide the neurons in the final stage of synaptic
      formation. Identifying these markers and unraveling the logic by which they
      direct synapse formation is a key challenge. Here, we address this task by
      constructing a probabilistic model that attempts to explain the neuronal
      connectivity diagram of C. elegans as a function of the expression patterns of
      its neurons. By only considering neuron pairs that are known to be connected by
      chemical or electrical synapses, we focus on the final stage of synapse
      formation, in which neurons identify their designated partners. Our results show
      that for many neurons the neuronal expression map of C. elegans can be used to
      accurately predict the subset of adjacent neurons that will be chosen as its
      postsynaptic partners. Notably, these predictions can be achieved using the
      expression patterns of only a small number of specific genes that interact in a
      combinatorial fashion.

PMID- 18711639
TI  - [Inequalities gender on health: challenges for the future].

PMID- 18711641
TI  - [Health Impact Assessment: assessing the effectiveness of policies in population
      health].
AB  - Health Impact Assessment is a comprehensive methodology proposed by the World
      Health Organization to determine the impact on health of projects, policies and
      strategies that are no originally specifically health-related but that could have
      on effect on health. This work aims to review the methodological approaches to
      Health Impact Assessment, and determine its value in Public Health. Health Impact
      Assessment is a multidisciplinary process that combines both qualitative and
      quantitative evidence in a decision-making frame. It is based on a model of
      health that includes the economic, political, social, psychological, and
      environmental determinants of health. If interventions with a real impact on the
      population s health require a comprehensive and structural approach, with Public
      Health measures taken at political level, those responsible for implementing such
      measures have to engage in the decision-making process and in the assessment of
      its effectiveness. To conduct Health Impact Assessment it is necessary to
      facilitate the integration of the existing data in order to perform the initial
      diagnosis and be able to investigate the late effects of the policy measures
      implemented. This way it will be possible to systematically monitor the effects
      on health of the actions which derive from Health Impact Assessment, thus
      maximizing potential positive effects on health and preventing the potential
      adverse effects.

PMID- 18711642
TI  - [European Union health strategy: public health for European people].
AB  - The member States have exclusive authority over health, but the European Union
      has the responsibility, pursuant to the provisions of Article 152 of the Treaty,
      of rounding out the policies of the member Status in order to enhance public
      health, prevent diseases and avoid sources of hazards to human health, which
      includes the fight against the most serious, widespread diseases (by supporting
      the research of their aetiology, their transmission and prevention), as well as
      health information and education and the surveillance of serious transborder
      threats to health, alerting in the event of such threats and combating the same.
      In order to fulfil these obligations, the European Commission presented the White
      Paper "Together for Health: A Strategic Approach for the EU 2008-2013" on October
      23, 2007. But the community-based health strategy has been being taking shape for
      some time now by means of different documents which have progressively been
      prefiguring it, thus being the result of long years of continuous work which has
      been being done since the early nineties. Throughout this time, the Directorate
      General of Public Health has been taking part in the process of preparing these
      documents and thus in what is now being presented as the EU health strategy. The
      main idea around which this work revolves is that there is a patent continuity
      and clear public health content in both the White Paper and in the documents
      which preceded it in time.

PMID- 18711640
TI  - [The Strengthening the Reporting of Observational Studies in Epidemiology
      (STROBE) statement: guidelines for reporting observational studies].
AB  - Much biomedical research is observational. The reporting of such research is
      often inadequate, which hampers the assessment of its strengths and weaknesses
      and of a study's generalisability. The Strengthening the Reporting of
      Observational Studies in Epidemiology (STROBE) initiative developed
      recommendations on what should be included in an accurate and complete report of
      an observational study. We defined the scope of the recommendations to cover
      three main study designs: cohort, case-control, and cross-sectional studies. We
      convened a 2-day workshop in September, 2004, with methodologists, researchers,
      and journal editors to draft a checklist of items. This list was subsequently
      revised during several meetings of the coordinating group and in e-mail
      discussions with the larger group of STROBE contributors, taking into account
      empirical evidence and methodological considerations. The workshop and the
      subsequent iterative process of consultation and revision resulted in a checklist
      of 22 items (the STROBE statement) that relate to the title, abstract,
      introduction, methods, results, and discussion sections of articles. 18 items are
      common to all three study designs and four are specific for cohort, case-control,
      or cross-sectional studies. A detailed explanation and elaboration document is
      published separately and is freely available on the websites of PLoS Medicine,
      Annals of Internal Medicine, and Epidemiology. We hope that the STROBE statement
      will contribute to improving the quality of reporting of observational studies.

PMID- 18711643
TI  - [Gender development inequalities epidemiology in Spain (1990-2000)].
AB  - BACKGROUND: Gender is an important health determinant for public health policies.
      This study describes the changes in gender development inequalities in Spain and
      its autonomous regions from 1990 to 2000. METHODS: An ecological study using the
      Human Development Index (HDI) and the Gender Development Index (GDI) was done.
      IDG both men and women was analysed according to indexes of education, income and
      life expectancy at birth. RESULTS: Although the GDI has had an increase of 5,05%
      in the 90 s, 51,5% of the population was located above the global GDI of Spain in
      1990, moreover this number decreased to 46,3% in 2000. Gender inequalities have
      been reduced both at national and regional levels. The regions with the lowest
      increase were Asturias (3.37%), Cantabria (3.68%) and Baleares Islands (3.71%).
      The regions with the highest increase were Madrid (6,46%) and Extremadura
      (6,75%). All the autonomous regions showed a number of GDI lower than the value
      of HDI. Both sexes achieved similar increase in life expectancy (Men: 5% and
      Women: 4%). An unequal variation was detected according to the autonomous region
      (Basque Country; Men: 7% and Women: 3%; Madrid; Men:8% and Women:5%). Women have
      improved their educational level in comparison to men (Men: 3% and Women: 6%). In
      the 90 s, men obtained more income than women, but women improved their situation
      three times more than men. CONCLUSIONS: Inequalities in Human Development
      analysed by gender have been reduced in the 90 s in Spain. However, the
      improvement of education, income and life expectancy occurred only in some
      autonomous regions. This situation shows the differences among Spanish autonomous
      regions.

PMID- 18711644
TI  - [Sociodemographic and health factors explaining emotional wellbeing as a quality
      of life domain of older people in Madrid, Spain. 2005].
AB  - BACKGROUND: The study of the emotional state and personal coping resources has
      drawn an increasing interest in the Quality of Life (QoL) field. Diverse
      researches have demonstrated its contribution to satisfaction with life, and the
      interconnection with other life domains of great importance in ageing, as health
      is. The aim of this work is to analyze the relationships of emotional wellbeing
      (in terms of affects and coping resources) with sociodemographic and health
      factors. METHODS: A survey on QoL among older people living in family housing of
      Madrid province (CadeViMa-2005) was used. Multivariate analyses were applied for
      generating an indicator of emotional wellbeing which integrated positive and
      negative affects, as well as personal coping resources. A logistic regression
      model was created to explain a positive emotional wellbeing, according to
      sociodemographic and health characteristics. RESULTS: People without anxiety or
      depression problems were around three times more likely to evaluate their
      emotional wellbeing positively than those who had problems. Older adults whose
      health was better than in the previous 12 months, seemed to be five times more
      likely to report a high emotional wellbeing, compared to those who experienced a
      health decline. Individuals with a very good perceived health status were 26
      times more likely of having a high emotional wellbeing than people with a
      negative health perception. Those with middle and upper social class were three
      times more likely to experience a positive emotional wellbeing than those
      belonging to a low social class. CONCLUSIONS: Health greatly influences emotional
      wellbeing with a relevant role of the subjective experience of health, together
      with social class as an indicator of educational level and socioeconomic status.

PMID- 18711645
TI  - [Relationship among the degree of control of arterial hypertension, comorbidity
      and costs in individuals over age 30 during 2006].
AB  - BACKGROUND: Arterial hypertension is one of the main reasons for primary care
      consultations. This study is aimed at determining the relationship among the
      degree to which arterial hypertension is controlled, comorbidity and the direct
      costs in primary care. METHODS: Retrospective, multi-centre design. Subjects over
      30 years of age pertaining to five primary care teams (2006) were included.
      CRITERIA: good control (<140/90 and <130/80 mmHg in diabetics and those with
      cardiovascular disease [CVD]. Main general measurements, CVD, Charlson index,
      casuistic/comorbidity (Adjusted Clinical Groups), clinical parameters and direct
      costs (fixed/semifixed and variable costs) [medications, tests and referrals])
      Logic regression and ANCOVA for correcting the model, p<0.05. RESULTS: The
      prevalence of arterial hypertension was 26.5% (mean age: 67.1 years; males:
      43.5%). Good control totalled 52.0% (CI: 51.2-52.8%). Poor control was
      independently related to diabetes (Odds Ratio=3.8), CVD (Odds Ratio=2.2) and
      males (Odds Ratio=1.2), p<0.001. The average/direct unit cost/year was 1,202.13
      Euro vs. 1,183.55 Euro (p=0.032). CONCLUSIONS: Those individuals whose arterial
      hypertension was poorly controlled displayed a greater burden of morbidity and a
      similar healthcare cost in comparison to those under good control.

PMID- 18711646
TI  - [Relationship between alcohol, drug use and traffic accidents related to
      nightlife among a Spanish youth sample in three autonomous communities in 2007].
AB  - BACKGROUND: The phenomenon known as binge drinking and other drug abuse
      frequently occurs among young people in nightlife-related areas. This study
      analyzes the risk behaviours and the accident rate related to alcohol and other
      drugs among a sample of young people involved in nightlife. METHOD: A total of
      440 young people from 3 Spanish Autonomous Communities took part. The sample size
      was estimated by means of Respondent Driven Sampling. The statistical analyses
      mined frequencies and measurements of the relationship of driving risk-related
      behaviour in relation to the accident rate, number of cases of drunkenness,
      frequency of accidents during the past month, influence of gender and age, as
      well as the predictiveness of these variables as regards the accident rate.
      RESULTS: A total of 50.2% of these young people had gotten into a vehicle with a
      driver who was drunk and/or under the influence of drugs, 23.2% has driven when
      drunk and 23.5% under the influence of drugs. The greater the degree of
      involvement in nightlife, the higher the frequency of drunkenness [ chi(2)
      (9)=112.24; p< .000 ] the greater the number of cases of drunkenness, the higher
      the frequency of these behaviors: getting into a vehicle with drivers who are
      drunk or under the influence of drugs [ c(2)=36,442, (3) p<0.001 ], drunken
      driving [ chi(2) =23,748, (3) p<0.001 ] and driving while under the influence of
      drugs [ chi(2)=23,816 (3) p<0.001 ]. The regression analysis highlighted drunken
      driving (odds-ratio=5.4) as the risk behaviour most related to traffic accidents.
      conclusions: There is a high incidence of risk behaviours while driving vehicles.
      Drunkenness, drug use and involvement in nightlife increase the frequency of
      these behaviours. Drunken driving was the best accident predictor.

PMID- 18711647
TI  - [Prevalence and incidence in Albacete, Spain, of Toxoplasma gondii infection in
      women of childbearing age: differences between immigrant and non-immigrant (2001
      2007)].
AB  - BACKGROUND: Strategies to prevent congenital toxoplasmosis must be adapted to the
      local epidemiology of Toxoplasma gondii infection. The objective of this study
      was to know the prevalence and the incidence of T. gondii infection in women of
      childbearing age in Albacete. METHODS: The source of information was the database
      of the Microbiology Laboratory of the Albacete General Hospital. To know the
      prevalence we reviewed the results of T. gondii IgG determinations from pregnant
      women living in the Albacete area who gave birth in 2006. To estimate the
      incidence we performed a longitudinal retrospective study of seronegative women
      with repeated T. gondii IgG determinations over at least one year. RESULTS:
      Prevalence study: We studied 2,623 pregnant women, of whom 21% were seropositive.
      Seroprevalence in Spain-born women was 16% (95% CI = 14%-17%) and it increased
      with age from 9% in women under 25 to 22% in women over 34 years old. Fifty-one
      per cent (95% CI=46%-56%) of the immigrant women were seropositive. Incidence
      study: We studied 2,416 women. The median time at risk was 35 months. There were
      5 confirmed and 3 possible seroconversions. The incidence was 0.7-1.1
      seroconversions per 1,000 women-year. CONCLUSIONS: Prevalence of T. gondii
      infection among Spain-born women is the lowest one of those published so far. The
      incidence of infection among women of childbearing age was low.

PMID- 18711648
TI  - [Women participation in clinical trials. A preliminary study in the files of the
      Spanish Agency for Medicinal Products and Medical Devices].
AB  - BACKGROUND: The evaluation of the gender bias in clinical trials is not
      unanimous. The aim of this study has been the assessment of the current situation
      in Spain regarding the manipulation of data from clinical trials at the
      publication of the Law of Equality. METHODS: We have examined the study design,
      sample population, demographic data and baseline clinical characteristics of
      participants, results and conclusions of the trial in the summaries of the final
      reports of clinical trials received in the first four months of 2007 in the
      Agencia Espanola de Medicamentos y Productos Sanitarios. RESULTS: From twenty
      five documents analysed, in their results and conclusions: Five subdivide data
      sets by age and gender, thirteen do not subdivide data by gender nor do they
      provide a conclusion, three do not subdivide results neither but do describe
      severe side effect by gender and four others provide no results or conclusions.
      CONCLUSIONS: Only twenty percent of the reviewed summaries provide data
      subdivided by gender. This could be due to the fact that it has not been made or
      that it was not given enough importance to include it in the summary, neither of
      which is satisfactory. A more detailed study is difficult due to the current
      quality of the summaries provided of the final reports of the clinical trials,
      which is the only document that is mandatory to send to the AEMPS once the trial
      has concluded. We expect that with the publication of the new Law of Equality
      this situation will improve, given the growing evidence of the relevance of the
      subdivision by gender.

PMID- 18711651
TI  - Primum non nocere. Quomo sapere?. Firstly, do no harm. How can we know this? Drug
      eluting stents versus surgery.

PMID- 18711652
TI  - Clinical formulas, mother's opinion and ultrasound in predicting birth weight.
AB  - CONTEXT AND OBJECTIVE: Accurate fetal weight estimation is important for labor
      and delivery management. So far, there has not been any conclusive evidence to
      indicate that any technique for fetal weight estimation is superior to any other.
      Clinical formulas for fetal weight estimation are easy to use but have not been
      extensively studied in the literature. This study aimed to evaluate the accuracy
      of clinical formulas for fetal weight estimation compared to maternal and
      ultrasound estimates. DESIGN AND SETTING: Prospective study involving 100 full
      term, cephalic, singleton pregnancies delivered within three days of fetal weight
      estimation. The setting was a tertiary public teaching hospital in Sao Paulo,
      Brazil. METHODS: Upon admission, the mother's opinion about fetal weight was
      recorded. Symphyseal-fundal height and abdominal girth were measured and two
      formulas were used to calculate fetal weight. An ultrasound scan was then
      performed by a specialist to estimate fetal weight. The four estimates were
      compared with the birth weight. The accuracy of the estimates was assessed by
      calculating the percentage that was within 10% of actual birth weight for each
      method. The chi-squared test was used for comparisons and p < 0.05 was considered
      significant. RESULTS: The birth weight was correctly estimated (+/- 10%) in 59%,
      57%, 61%, and 65% of the cases using the mother's estimate, two clinical
      formulas, and ultrasound estimate, respectively. The accuracy of the four methods
      did not differ significantly. CONCLUSION: Clinical formulas for fetal weight
      prediction are as accurate as maternal and ultrasound estimates.

PMID- 18711653
TI  - Estimation of absolute renal uptake with technetium-99m dimercaptosuccinic acid:
      direct comparison with the radioactivity of nephrectomy specimens.
AB  - CONTEXT AND OBJECTIVE: Studies using radionuclides are the most appropriate
      method for estimating renal function. Dimercaptosuccinic acid chelate labeled
      with technetium-99m (99mTc-DMSA) is the radiopharmaceutical of choice for high
      resolution imaging of the renal cortex and estimation of the functional renal
      mass. The aim of this study was to evaluate a simplified method for determining
      the absolute renal uptake (ARU) of 99mTc-DMSA prior to nephrectomy, using the
      radioactivity counts of nephrectomy specimens as the gold standard. DESIGN AND
      SETTING: Prospective study at the Division of Nuclear Medicine, Department of
      Radiology, Universidade Estadual de Campinas. METHODS: Seventeen patients (12
      females; range 22-82 years old; mean age 50.8 years old) underwent nephrectomy
      for various reasons. Renal scintigraphy was performed three to four hours after
      intravenous administration of a mean dose of 188.7 MBq (5.1 mCi) of 99mTc-DMSA,
      which was done six to 24 hours before surgery. The in vivo renal uptake of 99mTc
      DMSA was determined using the radioactivity of the syringe before the injection
      (measured using a dose calibrator) and the images of the syringe and kidneys,
      obtained from a scintillation camera. After surgery, the reference value for
      renal uptake of 99mTc-DMSA was determined by measuring the radioactivity of the
      nephrectomy specimen using the same dose calibrator. RESULTS: The ARU
      measurements were very similar to those obtained using the reference method, as
      determined by linear regression (r-squared = 0.96). CONCLUSION: ARU estimation
      using the proposed method before nephrectomy seems to be accurate and feasible
      for routine use.

PMID- 18711654
TI  - Material and human resources for neonatal resuscitation in public maternity
      hospitals in Brazilian state capitals.
AB  - CONTEXT AND OBJECTIVE: In 2002, the early neonatal mortality rate in Brazil was
      12.42 per thousand live births. Perinatal asphyxia was the greatest cause of
      neonatal death (about 23%). This study aimed to evaluate the availability of the
      resources required for neonatal resuscitation in delivery rooms of public
      hospitals in Brazilian state capitals. DESIGN AND SETTING: Multicenter cross
      sectional study involving 36 hospitals in 20 Brazilian state capitals in June
      2003. METHODS: Each Brazilian region was represented by 1-4% of its live births.
      A local coordinator collected data regarding physical infrastructure, supplies
      and professionals available for neonatal resuscitation in the delivery room. The
      information was analyzed using the Statistical Package for the Social Sciences,
      version 10. RESULTS: Among the 36 hospitals, 89% were referral centers for high
      risk pregnancies. Each institution had a monthly mean of 365 live births (3% <
      1,500 g and 15% < 2,500 g). The 36 hospitals had 125 resuscitation tables (3-4
      per hospital), all with overhead radiant heat, oxygen and vacuum sources.
      Appropriate equipment for pulmonary ventilation was available for more than 90%
      of the 125 resuscitation tables. On average, one pediatrician, three nurses and
      five nursing assistants per shift worked in the delivery rooms of each
      institution. Out of the 874 pediatricians and 1,037 nursing personnel that worked
      in the delivery rooms of the 36 hospitals, 94% and 22%, respectively, were
      trained in neonatal resuscitation. CONCLUSIONS: The main public maternity
      hospitals in Brazilian state capitals have the resources to resuscitate neonates
      at birth.

PMID- 18711655
TI  - Marginal grafts increase early mortality in liver transplantation.
AB  - CONTEXT AND OBJECTIVE: Expanded donor criteria (marginal) grafts are an important
      solution for organ shortage. Nevertheless, they raise an ethical dilemma because
      they may increase the risk of transplant failure. This study compares the
      outcomes from marginal and non-marginal graft transplantation in 103 cases of
      liver transplantation due to chronic hepatic failure. DESIGN AND SETTING: One
      hundred and three consecutive liver transplantations to treat chronic liver
      disease performed in the Liver Transplantation Service of Hospital das Clinicas
      da Faculdade de Medicina da Universidade de Sao Paulo between January 2001 and
      March 2006 were retrospectively analyzed. METHODS: We estimated graft quality
      according to a validated scoring system. We assessed the pre-transplantation
      liver disease category using the Model for End-Stage Liver Disease (MELD), as low
      MELD (< 20) or high MELD (>or= 20). The parameters for marginal and non-marginal
      graft comparison were the one-week, one-month and one-year recipient survival
      rates, serum liver enzyme peak, post-transplantation hospital stay and incidence
      of surgical complications and retransplantation. The significance level was 0.05.
      RESULTS: There were no differences between the groups regarding post
      transplantation hospital stay, serum liver enzyme levels and surgical
      complications. In contrast, marginal grafts decreased overall recipient survival
      one month after transplantation. Furthermore, low-MELD recipients of non-marginal
      grafts showed better one-week and one-month survival than did high-MELD
      recipients of marginal livers. After the first month, patient survival was
      comparable in all groups up to one year. CONCLUSION: The use of marginal graft
      increases early mortality in liver transplantation, particularly among high-MELD
      recipients.

PMID- 18711656
TI  - Factors affecting compliance with the measles vaccination schedule in a Brazilian
      city.
AB  - CONTEXT AND OBJECTIVE: The success of vaccination campaigns depends on the degree
      of adherence to immunization initiatives and schedules. Risk factors associated
      with children's failure to receive the measles vaccine at the correct age were
      studied in the city of Sao Paulo, Brazil. DESIGN AND SETTING: Case-control and
      exploratory study, in the metropolitan area of Sao Paulo. METHODS: The caregivers
      of 122 children were interviewed regarding their perceptions and understanding
      about the measles vaccination and the disease. RESULTS: The results showed that
      age, region of residence, marital status and education level were unrelated to
      taking measles vaccines adequately. Most individuals remembered being informed
      about the last annual vaccination campaign by television, but no communication
      channel was significantly associated with vaccination status. The answers to
      questions about knowledge of the disease or the vaccine, when analyzed alone,
      were not associated with taking measles vaccinations at the time indicated by
      health agencies. The results showed that, when parents felt sorry for their
      children who were going to receive shots, they delayed the vaccination. Most of
      the children did not take the measles vaccination on the exactly recommended
      date, but delayed or anticipated the shots. CONCLUSION: It is clear that there is
      no compliance with the government's recommended measles vaccination schedule
      (i.e. first dose at nine and second at 15 months of age, as recommended in 1999
      and 2000). Feeling sorry for the children receiving shots can delay vaccination
      taking.

PMID- 18711657
TI  - Expression of MRP1 gene in acute leukemia.
AB  - CONTEXT AND OBJECTIVE: Overexpression of the multidrug resistance-associated
      protein 1 (MRP1) gene has been linked with resistance to chemotherapy in vitro,
      but little is known about its clinical impact on acute leukemia patients. Our aim
      was to investigate the possible association between MRP1 gene expression level
      and clinical outcomes among Iranian leukemia patients. DESIGN AND SETTING: This
      was an analytical cross-sectional study on patients referred to the Hematology,
      Oncology and Stem Cell Research Center, Sharyatee Public Hospital, whose
      diagnosis was acute myelogenous leukemia (AML) or acute lymphoblastic leukemia
      (ALL). All molecular work was performed at NIGEB (public institution). METHODS:
      To correlate with prognostic markers and the clinical outcome of acute leukemia,
      MRP1 gene expression was assessed in 35 AML cases and 17 ALL cases, using the
      quantitative real-time polymerase chain reaction and comparing this to the
      chemotherapy response type. RESULTS: Mean expression in AML patients in complete
      remission (0.032 +/- 0.031) was significantly lower than in relapsed cases (0.422
      +/- 0.297). In contrast, no significant difference in MRP1 mRNA level was
      observed between complete remission and relapsed ALL patients. There was a
      difference in MRP1 expression between patients with unfavorable and favorable
      cytogenetic prognosis (0.670 +/- 0.074 and 0.028 +/- 0.013, respectively). MRP1
      expression in M5 was significantly higher (p-value = 0.001) than in other
      subtypes. CONCLUSIONS: The findings suggest that high MRP1 expression was
      associated with poor clinical outcome and was correlated with the M5 subtype and
      poor cytogenetic subgroups among AML patients but not among ALL patients.

PMID- 18711658
TI  - Are distal radius fracture classifications reproducible? Intra and interobserver
      agreement.
AB  - CONTEXT AND OBJECTIVE: Various classification systems have been proposed for
      fractures of the distal radius, but the reliability of these classifications is
      seldom addressed. For a fracture classification to be useful, it must provide
      prognostic significance, interobserver reliability and intraobserver
      reproducibility. The aim here was to evaluate the intraobserver and interobserver
      agreement of distal radius fracture classifications. DESIGN AND SETTING: This was
      a validation study on interobserver and intraobserver reliability. It was
      developed in the Department of Orthopedics and Traumatology, Universidade Federal
      de Sao Paulo - Escola Paulista de Medicina. METHOD: X-rays from 98 cases of
      displaced distal radius fracture were evaluated by five observers: one third-year
      orthopedic resident (R3), one sixth-year undergraduate medical student (UG6), one
      radiologist physician (XRP), one orthopedic trauma specialist (OT) and one
      orthopedic hand surgery specialist (OHS). The radiographs were classified on
      three different occasions (times T1, T2 and T3) using the Universal (Cooney),
      Arbeitsgemeinschaft fur Osteosynthesefragen/Association for the Study of Internal
      Fixation (AO/ASIF), Frykman and Fernandez classifications. The kappa coefficient
      (kappa) was applied to assess the degree of agreement. RESULTS: Among the three
      occasions, the highest mean intraobserver k was observed in the Universal
      classification (0.61), followed by Fernandez (0.59), Frykman (0.55) and AO/ASIF
      (0.49). The interobserver agreement was unsatisfactory in all classifications.
      The Fernandez classification showed the best agreement (0.44) and the worst was
      the Frykman classification (0.26). CONCLUSION: The low agreement levels observed
      in this study suggest that there is still no classification method with high
      reproducibility.

PMID- 18711659
TI  - Scapular fracture: lower severity and mortality.
AB  - CONTEXT AND OBJECTIVE: The presence of scapular fracture is believed to be
      associated with high rates of other injuries and accompanying morbidities. The
      aim was to study injury patterns and their overall outcomes in patients with
      scapula fractures. DESIGN AND SETTING: Cross-sectional study of trauma patients
      treated at six general hospitals in Tehran. METHODS: One-year trauma records were
      obtained from six general hospitals Among these, forty-one had sustained a
      scapular fracture and were included in this study. RESULTS: Scapular fracture
      occurred predominantly among 20 to 50-year-old patients (78%). Road traffic
      accidents (RTAs) were the main cause of injury (73.2%; 30/41). Pedestrians
      accounted for 46.7% (14/30) of the injuries due to RTAs. Falls were the next most
      common cause, accounting for seven cases (17.1%). Body fractures were the most
      common type of scapular fractures (80%). Eighteen patients (43.9%) had isolated
      scapular fractures. Limb fracture was the most common associated injury, detected
      in 18 cases (43.9%). Three patients (7.3%) had severe injuries (injury severity
      score, ISS >or= 16) which resulted in one death (2.4%). The majority of the
      patients were treated conservatively (87.8%). CONCLUSIONS: Patients with scapula
      fractures have more severe underlying chest injuries and clavicle fractures.
      However, this did not correlate with higher rates of injury severity score,
      intensive care unit admission or mortality.

PMID- 18711660
TI  - Postmenopausal intestinal obstructive endometriosis: case report and review of
      the literature.
AB  - CONTEXT: Endometriosis is characterized by the presence of endometrial tissue
      outside the uterine cavity, which is commonly detected in gynecological practice
      but rarely reported as a coloproctological disorder. The objective of the present
      report was to discuss a rare case of postmenopausal intestinal endometriosis
      simulating a malignant lesion, following a review of the literature. CASE REPORT:
      A 74-year-old woman with complaints of hematochezia and tenesmus of two months'
      duration accompanied by liquid feces and pelvic pain, but with no other
      gastrointestinal or gynecological complaints, was referred to our service. She
      had been menopausal for 22 years, with no hormone replacement treatment, and had
      undergone panhysterectomy three years before the referral to us, due to
      endometrial thickening and a right adnexal cyst. Five months before this
      referral, she had undergone laparotomy due to acute obstructive abdomen, which
      revealed a tumor mass involving the small bowel. Anatomopathological examination
      of the enterectomy suggested a hypothesis of intestinal endometriosis. A
      proctological examination was normal. Computed tomography of the pelvis revealed
      thickening of the rectosigmoid transition and colonoscopy revealed friable tumor
      formation in the rectum. A biopsy of the lesion revealed mucosal fragments of
      endometrial type, which led to a review of the previous anatomopathological
      examination. The patient underwent rectosigmoidectomy with protective
      transversotomy, with a good postoperative course, and anatomical examination
      confirmed the intestinal endometriosis. The patient subsequently suffered a
      stenosing recurrence of the lesion and has undergone colostomy since then.

PMID- 18711661
TI  - Surgical treatment of renal cell carcinoma recurrence at the renal fossa
      following radical nephrectomy.
AB  - CONTEXT: Isolated renal cell carcinoma recurrence at the renal fossa is a rare
      event. This condition occurs in 1 to 2% of radical nephrectomy cases. It is
      usually seen in postoperative follow-up imaging examinations such as abdominal
      computed tomography or abdominal ultrasound. There is controversy among
      urologists and oncologists regarding the best way to treat this rare situation,
      because of the few cases in the literature. CASE REPORT: We report on a case of
      isolated recurrence at the renal fossa due to renal cell carcinoma (RCC), four
      and a half years after radical nephrectomy, without evidence of metastases in
      other organs. The diagnosis was made from abdominal tomography performed during
      outpatient follow-up, in which a retroperitoneal mass was observed in the renal
      fossa. Excision was carried out by means of a subcostal transversal incision,
      without complications. One and a half years after the procedure, there was
      evidence of metastasis in the left lung and, six months later, another recurrence
      at the ninth anterior right rib, while the patient remained asymptomatic.
      Aggressive surgical treatment is a good method for controlling this rare
      situation of single retroperitoneal RCC recurrence. Abdominal tomography must
      continue to be performed over long periods of follow-up, to monitor for RCC
      following radical nephrectomy, in order to diagnose any late retroperitoneal
      recurrences. These must be treated as single RCC metastases.

PMID- 18711662
TI  - The male biological clock is ticking: a review of the literature.
AB  - The term biological clock is usually used by physicians and psychologists to
      refer to the declining fertility, increasing risk of fetal birth defects and
      alterations to hormone levels experienced by women as they age. Female fecundity
      declines slowly after the age of 30 years and more rapidly after 40 and is
      considered the main limiting factor in treating infertility. However, there are
      several scientific reports, chapters in books and review articles suggesting that
      men may also have a biological clock. The aim of our study was to conduct a
      review of the literature, based on the Medical Literature Analysis and Retrieval
      System Online (Medline), to evaluate the male biological clock. After adjustments
      for other factors, the data demonstrate that the likelihood that a fertile couple
      will take more than 12 months to conceive nearly doubles from 8% when the man is
      < 25 years old to 15% when he is > 35 years old. Thus, paternal age is a further
      factor to be taken into account when deciding on the prognosis for infertile
      couples. Also, increasing male age is associated with a significant decline in
      fertility (five times longer to achieve pregnancy at the age of 45 years).
      Patients and their physicians therefore need to understand the effects of the
      male biological clock on sexual and reproductive health, in that it leads to
      erectile dysfunction and male infertility, as well as its potential implications
      for important medical conditions such as diabetes and cardiovascular diseases.

PMID- 18711663
TI  - Publish or perish: a provocation.

PMID- 18711664
TI  - Studies on the inhibition of Moloney murine leukemia virus reverse transcriptase
      by N-tritylamino acids and N-tritylamino acid-nucleotide compounds.
AB  - N-Acylated derivatives of 8-(6-aminohexyl) amino-adenosine-5 '-phosphate were
      prepared and studied with regard to their effect on DNA synthesis by the Moloney
      leukemia virus reverse transcriptase. N-palmitoyl and N-nicotinyl derivatives and
      bis-8-(6-aminohexyl) amino-5'-AMP inhibited the enzyme partially using poly
      (rA).oligo d(pT)(16-18) as template-primer with [(3)H]dTTP. In order to increase
      hydrophobicity in the acyl component tethered to the 8-(6-aminohexyl) amino group
      on the adenine nucleotide, N-trityl-L-phenylalanine and the N-trityl derivatives
      of the o, m, and p-fluoro-DL-phenylalanine were initially examined for inhibition
      of the enzyme using the above template-primer system. The compounds all inhibited
      the reverse transcriptase with IC(50) values of approximately 60-80 microM.
      However, when N-trityl-m-fluoro-DL-phenylalanine was coupled to the nucleotide 8
      (6-aminohexyl) amino-adenosine-5'-phosphate, the inhibitory activity of this
      compound increased significantly (IC(50) = 5 microM).

PMID- 18711665
TI  - Process research on the preparation of DMT protected 2'-O-methoxyethylguanosine
      for oligonucleotide synthesis in therapeutic applications.
AB  - An optimized process to synthesize DMT protected 2 '-O-methoxyethylguanosine is
      described. A key step involves the enzymatic deamination of a mixture of
      alkylated products to selectively afford the desired material without resorting
      to chromatography for purification. This approach was scaled up to kilogram
      quantities for use in oligonucleotide therapeutics. [Formula: see text].

PMID- 18711666
TI  - New sulphonamide and carboxamide derivatives of acyclic C-nucleosides of triazolo
      thiadiazole and the thiadiazine analogues. Synthesis, anti-HIV, and antitumor
      activities. Part 2.
AB  - A new series of acyclic C-nucleosides 1',2'-O-isopropylidene-D-ribo-tetritol-1
      yl)[1,2,4] triazolo[3,4-b][1,3,4]thiadiazoles bearing arylsulfonamide (5-8) and
      arylcarboxamide (9-12) residues have been synthesized under microwave
      irradiation. Thiadiazines 13-15 have been analogously prepared, and upon acid
      hydrolysis, afforded the free nucleosides 16-18. The new synthesized compounds
      were assayed against HIV-1 and HIV-2 in MT-4 cells. Compound 7 was also screened
      against a panel of tumor cell lines consisting of CD4 human T-cells.

PMID- 18711667
TI  - Novel enamine derivatives of 5,6-dihydro-2'-deoxyuridine formed in reductive
      amination of 5-formyl-2'-deoxyuridine.
AB  - Reductive amination of 5-formyl-3',5'-di-O-acetyl-2'-deoxyuridine with primary
      amines and sodium triacetoxyborohydride (NaBH(OAc)(3)) afforded novel enamine
      derivatives of 5,6-dihydro-2'-deoxyuridine as a result of unexpected 1,4
      conjugate reduction of intermediate Schiff bases in addition to the secondary
      amine derivatives of 2'-deoxyuridine, typical 1,2-reduction products.

PMID- 18711668
TI  - Synthesis and evaluation of antimicrobial activity of some pyrimidine glycosides.
AB  - Reaction of ethyl 4-thioxo-3,4-dihydropyrimidine-5-carboxylate derivatives 1a,b
      and ethyl 4-oxo-3,4-dihydropyrimidine-5-carboxylate 1c with 2,3,4,6-tetra-O
      acetyl-alpha-D-glucopyranosyl bromide in KOH or TEA afforded ethyl 2-aryl-4
      (2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosylthio or/ oxy)-6-methylpyrimidine
      5-carboxylate 6a-c. The glucosides 6a and 6b were obtained by the reaction of 1a
      and 1b with peracetylated glucose3 under MW irradiation. Mercuration of 1a
      followed by reaction with acetobromoglucose gave the same product 6a. The
      reaction of 1a-c with peracetylated ribose 4 under MW irradiation gave ethyl 2
      aryl-4-(2',3',5'-tri-O-acetyl-beta-D-ribofuranosylthio)-6-methylpyrimidine-5
      carboxylate 8a-c. The deprotection of 6a-c and 8a-c in the presence of methanol
      and TEA/H(2)O afforded the deprotected products 7a-c and 9a-c. The structure were
      confirmed by using (1)H and (13)CNMR spectra. Selected members of these compounds
      were screened for antimicrobial activity.

PMID- 18711669
TI  - Long, processive enzymatic DNA synthesis using 100% dye-labeled terminal
      phosphate-linked nucleotides.
AB  - We demonstrate the efficient synthesis of DNA with complete replacement of the
      four deoxyribonucleoside triphosphate (dNTP) substrates with nucleotides carrying
      fluorescent labels. A different, spectrally separable fluorescent dye suitable
      for single molecule fluorescence detection was conjugated to each of the four
      dNTPs via linkage to the terminal phosphate. Using these modified nucleotides,
      DNA synthesis by phi 29 DNA polymerase was observed to be processive for products
      thousands of bases in length, with labeled nucleotide affinities and DNA
      polymerization rates approaching unmodified dNTP levels. Results presented here
      show the compatibility of these nucleotides for single-molecule, real-time DNA
      sequencing applications.

PMID- 18711670
TI  - Metalloregulation of triple helix formation by control of the loop conformation.
AB  - The flexible polypyridine ligand, 2,2':6',2('')-terpyridine (terpy), was built
      into the backbone of oligonucleotides to form DNA conjugates. The terpy unit
      functioned as a good loop when the conjugates formed the bimolecular triplexes
      with complementary oligopurine. The triplex structure was destabilized by the
      specific interaction with divalent transition metal ions (Cu(2+), Zn(2+), and
      Fe(2+)), in particular Cu(2+) ions. This ion destabilized one of the triplexes by
      4.2 kcalmol(-1) or made the triplex formation constant less than 1/10(3) at 298
      K. This result is attributed to the substantial turbulence of the terminal
      structure of the triplexes.

PMID- 18711673
TI  - Comments on new technology--Endoscopic ultrasonography (EUS) routine method and
      new applications.

PMID- 18711672
TI  - Large intra-hepatic arterio-portal fistula following liver trauma.

PMID- 18711681
TI  - [Introduction--emergency ultrasonography].

PMID- 18711689
TI  - [Medical ultrasound imaging].

PMID- 18711690
TI  - Variety of angiotensin receptors in 3T3-L1 preadipose cells and differentiated
      adipocytes.
AB  - A local paracrine acting angiotensin (ANG) system of preadipocytes and mature
      adipocytes is involved in metabolic effects and tissue differentiation. The
      present study reports on the investigation of binding affinities for various
      angiotensin receptors including their relevance in 3T3-L1 adipocytes and
      preadipocytes and 3T3-442A preadipocytes. Competitive binding studies using both
      125I-ANG II and its more stable analogue 125I-SARILE for investigating AT1/AT2
      binding sites in 3T3-L1 preadipocytes reveal a biphasic competition curve with
      KDs at a low and high nanomolar range. By using the AT2 receptor selective ligand
      125I-CGP4112A the presence of high affinity AT2 binding sites in preadipocytes
      was observed. High nonspecific binding and a low receptor number is
      characteristic for all these experiments. An AT4 binding site (binding site for
      ANG IV) exists in 3T3-L1 and F442A preadipocytes and adipocytes with a high
      nanomolar KD. This low binding affinity was confirmed by a biological assay, the
      IRAP assay (=insulin regulated aminopeptidase assay). IRAP is associated with the
      AT4 receptor, which is a binding site at the luminal part of membrane bound IRAP.
      The curves for competition binding and for inhibition of IRAP activity are
      superimposable with respect to angiotensin IV. In conclusion, AT1 and AT2 binding
      sites are present in preadipocytes. AT2 receptor binding affinities are shown in
      preadipocytes for the first time. The description of a non-AT1/AT2 binding site
      with low affinity remains speculative albeit of high interest because
      antidiabetic and obesity related effects of angiotensin peptides and sartanes as
      antagonists are observed at these high concentrations. Local concentrations of
      ANG II and their degradation products may be extremely high. The low amounts of
      AT1 and AT2 binding sites emphasize the relevance of other binding sites in
      adipose tissue development and metabolic effects. The AT4 binding site seems to
      be one of the predominant receptors in adipose cells. Other degraded, but still
      bioactive peptides like ANG III, IV and ANG(1-7), activating receptors not
      influenced by ANG II, could be of importance.

PMID- 18711691
TI  - Differential expression of IGF-I and insulin receptor isoforms in HPV positive
      and negative human cervical cancer cell lines.
AB  - Human papillomavirus (HPV) is the main risk factor for cervical cancer; however,
      some carcinomas occur in the absence of the virus. IGF-IR and an isoform of the
      insulin receptor, IR-A, play important roles in cancer. In this study we assessed
      the role of the IGF/insulin receptors in cervical cancer cell lines with
      different HPV status, SiHa (HPV positive), and C33a (HPV negative). Different
      patterns of receptor expression were found; while SiHa expressed IGF-IR, IR-A and
      IR-B, and IR/IGF-IR hybrid receptors, C33a cells expressed the IR-A only.
      Tyrosine phosphorylation of these receptors in response to their corresponding
      ligands correlated with the expression level of these receptors in the cell
      lines. Activation of PI3-K and MAPK pathways was revealed in both cell lines,
      however, no effects on proliferation, migration, or invasion were observed. Here
      we show that cervical cancer cell lines--positive and negative for HPV--differ in
      the type of insulin and IGF-1 receptors expressed. Additional studies are needed
      for characterization of the role of IR-A in cervical carcinogenesis.

PMID- 18711692
TI  - Rosiglitazone reduces angiotensin II and advanced glycation end product-dependent
      sustained nuclear factor-kappaB activation in cultured human proximal tubular
      epithelial cells.
AB  - Tubular damage is a major feature in the development of diabetic nephropathy.
      This study investigates the effects of the thiazolidindione rosiglitazone on
      angiotensin II and advanced glycation end product-induced tubular activation in
      human proximal tubular epithelial cells IN VITRO. Angiotensin II and advanced
      glycation end products, both induced a dose-dependent sustained activation of the
      redox-sensitive transcription factor, Nuclear Factor KAPPA B (NF-kappaB). Nuclear
      translocation of NF-kappaB was evident already after one hour and persistent for
      more than four days. Co-incubation of proximal tubular epithelial cells with
      rosiglitazone significantly reduced angiotensin II and advanced glycation end
      product-mediated generation of reactive oxygen species, angiotensin II-dependent
      advanced glycation end product formation, NF-kappaB activation, and NF-kappaB
      dependent pro inflammatory gene expression. Most importantly, rosiglitazone
      effects on NFkappaB activation were maximal at later time points, indicating that
      rosiglitazone treatment confers long lasting renoprotective effects.

PMID- 18711693
TI  - Enzyme immunoassay of testosterone, 17beta-estradiol, and progesterone in
      perspiration and urine of preadolescents and young adults: exceptional levels in
      men's axillary perspiration.
AB  - Enzyme immunoassays for testosterone, 17beta-estradiol, and progesterone were
      validated for human facial and axillary perspiration and compared to levels in
      urine. In study 1, these assays were applied to samples from preadolescent girls
      and boys and young women and men. Men's axillary perspiration contained
      substantially higher levels of steroids than seen in other substrates from men or
      in any sample from women, boys, and girls. Male axillary steroid levels were very
      variable across individuals, and on average they exceeded levels in facial
      perspiration by 90-fold for testosterone and 45-fold for estradiol. Men's urinary
      testosterone also exceeded urinary levels of the other subjects. In study 2,
      axillary perspiration, urine, and saliva were collected from young men.
      Substantial axillary levels of testosterone and estradiol were again observed.
      Correlations of the same hormone among the different substrates were generally
      very low, except for a small correlation between estradiol levels measured in
      axillary perspiration and urine in study 2. High unconjugated steroid content in
      men's axillary excretions could, if absorbed by women during intimacy, be
      implicated in pheromonal activity.

PMID- 18711694
TI  - [A new procedure for the estimation of physical fitness of patients during
      clinical rehabilitation using the 6-minute-walk-test].
AB  - AIMS OF THE INVESTIGATION: The 6-minute-walk-test (6-MW) is an effective tool for
      measuring physical fitness in elderly patients. The increased walking distance is
      taken as a parameter for improved physical conditions. Frequently an unaltered
      walking distance is found after clinical treatment, but heart rate is
      significantly lower in the second challenge, indicating an improved physical
      fitness. This positive effect is not recognised when only the walking distance is
      analysed. METHODS: An analysis of the 6-MW test was performed on 263 patients
      before and after 3 - 4 weeks clinical rehabilitation. In a control group of 26
      patients 6-MW was repeated after recovery at the beginning and the end of the
      clinical treatment. Instrumented by a mobile pulse oximeter for recording oxygen
      saturation and heart rate, patients were instructed to walk as fast as they can
      do during 6 minutes. Measurements were performed every 30 seconds and printed
      out. Two new parameters, efficiency (E = S/f (C)), the ratio of distance and mean
      heart rate, and the theoretical increase in walking distance (S (z) = Delta f
      (C1)/Delta f (C2) x S (2) - S (1)) were introduced and tested. S (z) =
      theoretical increase in distance, Delta f (C1) = difference in heart rate at rest
      and mean heart rate at steady state during the first walk test with distance, S1.
      Delta f (C2), and S2 are measured during the second walk. Thus, the increase in
      distance is calculated under the assumption that the second walk test would have
      been performed by the patient with the same difference in heart rate that he/she
      achieved in the first walk. RESULTS: The patient groups walked 353 +/- 80 m at
      106 +/- 14.3 beats/min in the 1st. 6-MW and 368 +/- 76.9 m at a heart rate of 105
      +/- 14.0 beats/min in the final test. The increase of the walking distance was
      most significant in patients with shorter distances in the 1st 6-MW. A
      significant increase in the walking distance and in efficiency was found in
      patients with shorter walking distances or lower heart rates in the final test,
      using the numerical procedure described above. CONCLUSIONS: The patient's
      performance of the second walk test with an unchanged distance at a lower heart
      rate reveals an improved physical fitness. This is solely described by an
      increase by the parameter of efficiency, E. The calculation of the parameter, Sz,
      theoretical difference in walking distance (i. e., theoretical increase in almost
      all tests) provides a quantification of the effect of exercise training, even if
      the patient is not cooperative during the tests. Both parameters have proved to
      be suitable estimations for the assessment of physical fitness as a beneficial
      effect of clinical rehabilitation.

PMID- 18711695
TI  - [Pleural metastases of a typical bronchial carcinoid 7 years after lobectomy].
AB  - BACKGROUND: Bronchial carcinoids are a rare differential diagnosis of solitary
      pulmonary nodes. Because of their typical manifestation in the major bronchi,
      carcinoid tumours are visible regularly via bronchoscopy where they show a
      typical picture. In lymph node-negative disease a favourable outcome can be
      expected. Typically metastases develop in the lung, liver, brain, bone and
      adrenal glands. CASE REPORT: Seven years after lobectomy of a bronchial
      carcinoid, a slow-growing thickening of the pleura parietalis was noted in a 54
      year-old male patient. No clinical signs of neuroendocrine activity were seen.
      The histological diagnosis of pleural metastases was established via trans
      thoracic punctation. Pleural metastases of bronchial carcinoids are extremely
      rare. Only two other cases have been reported so far. Palliative cytotoxic
      chemotherapy was started. CONCLUSIONS: The postoperative prognosis of bronchial
      carcinoids in lymph node-negative disease is excellent. Metastatic disease--as in
      the rare case of pleural metastases shown here--remains a therapeutic dilemma.
      Extensively evaluated concepts for adjuvant or palliative settings do not exist.
      Further research is needed.

PMID- 18711696
TI  - [Microsleep, sleepiness and driving performance in patients with sleep apnoea
      syndrome].
AB  - Especially during monitoring activities or car driving needing high vigilance,
      episodes of microsleep are extremely dangerous. Microsleep can be described by
      observing behaviour patterns or electrophysiological parameters. An early
      recognition of these episodes is desirable. In the automobile industry intensive
      development is ongoing to register sleepiness and subsequent microsleep during
      driving to avoid accidents. The monitoring of eyelid frequency and diameter of
      the pupil (eye tracking) are most promising. Compared with a reference
      population, the accident risk of patients with sleep-related breathing disorders
      is more than two-fold higher. But up to now there are no definitive criteria-
      neither subjective nor objective tests such as, for instance, driving simulators-
      to predict driving impairment. By means of screening examinations, patients with
      obstructive sleep apnoea syndrome (OSAS) should be detected because therapy with
      CPAP normalises the accident rate. A further measure to reduce the risk of
      accidents is the so-called alertness management where techniques are communicated
      to detect and avoid sleeping episodes.

PMID- 18711697
TI  - Prevalence, incidence and clearance of human papillomavirus infection among young
      primiparous pregnant women in Kampala, Uganda.
AB  - The proportion of women who have already been exposed to human papillomavirus
      (HPV) infection by the time they first become pregnant, and the influence of
      pregnancy and delivery on the course of HPV infection are unclear. In Kampala,
      Uganda, 987 young primiparous pregnant women aged <25 years had gynaecological
      examination and liquid-based cytology. In the follow-up, women acted as their own
      controls, i.e., 1st/2nd versus 3rd trimesters (105 women), and during pregnancy
      versus after delivery (289 women). HPV was assessed using highly sensitive PCR
      assays. Prevalence of HPV and HIV infections at baseline were 60.0% and 7.3%,
      respectively. HPV16 and 18 were detected in 8.4% and 5.8%, respectively, i.e.,
      less frequently than HPV51 (8.7%) and 52 (12.1%). At follow-up new HPV infections
      were detected in 42.9% of women between the 1st/2nd and 3rd trimesters, and 38.1%
      between pregnancy and delivery, but 50.4% and 71.8% of HPV infections,
      respectively, cleared, leaving HPV prevalence unchanged in the different periods.
      Prevalence of cytological abnormalities diminished after delivery (from 21.2% to
      12.4%). Presence of genital warts and sexually transmitted infections other than
      HPV were the strongest risk factors for prevalent or incident HPV infection.
      Clearance was lower among HIV-positive women. In conclusion, HPV prevalence was
      high in primiparous women in Uganda, but pregnancy did not seem to be a period of
      special vulnerability to the infection.

PMID- 18711699
TI  - Validation of quality indicators for radical prostatectomy.
AB  - The feasibility and validity of proposed radical prostatectomy quality indicators
      has not been well studied. We assessed indicator availability from treating
      charts. We tested the convergent construct validity of a modified subset that
      were available from this information source by correlating them to hospital
      prostatectomy volume, a variable repeatedly associated with the quality of
      surgical care. The study population consisted of a stratified random sample of
      prostate cancer patients who were: (i) diagnosed between 1990 and 1998 in Ontario
      and (ii) treated by radical prostatectomy with curative intent within 6 months of
      diagnosis (n = 645). Of the 9 candidate quality indicators assessed, 4 were
      missing for 25-56% of study subjects and were not analyzed further. We discuss
      the implications of this missing information on feasibility of their use. For
      blood transfusions of 3 units or greater, length of hospital stay and use of non
      nerve-sparing surgical technique, worse outcomes were generally apparent with
      decreasing hospital volume. Acute complication rates and positive surgical margin
      rates did not increase with decreasing hospital volume. We were able to
      demonstrate convergent construct validity for 3 quality indicators. Upon further
      validation, this readily available information may be applied to aid providers
      and quality councils to more effectively identify problems and guide change in
      the management of early prostate cancer.

PMID- 18711698
TI  - Effect of obesity and other lifestyle factors on mortality in women with breast
      cancer.
AB  - A few lifestyle characteristics before cancer diagnosis have been suggested to
      modify the prognosis of breast cancer. Follow-up information from 1,453 women
      with incident invasive breast cancer, diagnosed between 1991 and 1994 and
      interviewed within the framework of an Italian multicenter case-control study,
      was used to assess the effect of obesity and of a large spectrum of other factors
      on breast cancer mortality. Five hundred and three deaths, including 398 breast
      cancer deaths, were identified. Hazard ratios (HR) for all-cause and breast
      cancer mortality and corresponding 95% confidence intervals (CI), were calculated
      using Cox proportional hazards models and adjusted for age and breast cancer
      characteristics (stage and receptor status). Increased risk of death for breast
      cancer emerged for body mass index (BMI) >/= 30 kg/m(2) (HR = 1.38; 95% CI: 1.02
      1.86), compared to <25, or waist-to-hip ratio (WHR) >/= 0.85 (HR = 1.27; 95% CI:
      0.98-1.64), compared to <0.80, and the strongest association was observed for
      women with BMI >/=30 and high WHR (>/=0.85), compared to women with BMI <25 and
      WHR < 0.85 (HR = 1.57, 95% CI: 1.08-2.27). The unfavorable effect of high BMI was
      similar in women <55 and >/=55 years of age, whereas it was stronger in women
      with I-II stage than III-IV stage breast cancer. Low vegetable and fruit
      consumption and current or past smoking were also associated to marginally worse
      breast cancer survival. No significant relationship with survival after breast
      cancer emerged for several other major lifestyle factors, including physical
      activity, alcohol drinking, exogenous hormones use and fat intake. High BMI was
      the lifestyle risk factor that most consistently modified breast cancer prognosis
      in our study.

PMID- 18711701
TI  - Reproductive, menstrual, and other hormone-related factors and risk of renal cell
      cancer.
AB  - A role of hormone-related factors in renal cell cancer (RCC) etiology has been
      hypothesized, but the epidemiological evidence is inconsistent. The present study
      aimed at evaluating the effect of reproductive, menstrual and other gender
      specific variables on RCC risk among women. This study is part of a larger
      hospital-based, case-control study on RCC risk, conducted in northern, central
      and southern Italy. Cases were 273 women, below age 80, with histologically
      confirmed, incident RCC. Controls were 546 women hospitalized for acute,
      nonneoplastic conditions, frequency-matched to cases by age and center. Odds
      ratios (OR) and 95% confidence intervals (CI) were computed using multiple
      logistic regression models. RCC risk was inversely related to age at first birth
      (OR = 0.7, 95% CI 0.5-1.0, for >/= 25 years vs. <25 years). Hysterectomy was
      found to double RCC risk (OR = 2.3, 95% CI 1.3-4.2). A negative association of
      borderline-statistical significance emerged for age at menarche, whereas, no
      associations were found between RCC risk and parity, menopausal status, age at
      menopause and use of hormone replacement therapy or oral contraceptives. Our
      findings give support to a role of hysterectomy in increasing RCC risk without
      corroborating, however, a major role of female hormone-related factors.

PMID- 18711700
TI  - Coffee consumption and risk of endometrial cancer: a prospective study in Japan.
AB  - Coffee has been proposed to decrease the circulating insulin and estrogen levels,
      which are related to the development of endometrial cancer. However, few studies
      have prospectively assessed the association between coffee consumption and
      endometrial cancer. We conducted a population-based prospective cohort study in
      53,724 Japanese women aged 40-69 years with no history of cancer at baseline in
      1990-1994. We used Cox proportional hazards regression analysis to estimate the
      hazard ratio (HR) and 95% confidence interval (CI) of endometrial cancer
      incidence in relation to coffee consumption. All reported p values are 2-tailed.
      During the 15-year follow-up period, we documented 117 cases of endometrial
      cancer. Coffee consumption was significantly associated with a decreased risk of
      endometrial cancer. After adjustment for age, study area, body mass index,
      menopausal status, age at menopause for postmenopausal women, parity, use of
      exogenous female hormones, smoking status and by consumption of green vegetables,
      beef, pork and green tea, the multivariate HRs (95% CI) of endometrial cancer in
      women who drank coffee </=2 days/week, 3-4 days/week, 1-2 cups/day and >/=3
      cups/day were 1.00, 0.97 (0.56-1.68), 0.61 (0.39-0.97) and 0.38 (0.16-0.91),
      respectively (p for trend = 0.007). In contrast, green tea consumption was not
      significantly associated with a reduced risk of endometrial cancer (p for trend =
      0.22). The inverse association between coffee consumption and risk of endometrial
      cancer was consistently observed in subgroup analyses stratified by potential
      confounders. Coffee consumption may be associated with a decreased risk of
      endometrial cancer.

PMID- 18711702
TI  - Hypermethylation of E-cadherin is an independent predictor of improved survival
      in head and neck squamous cell carcinoma.
AB  - BACKGROUND: The loss of E-cadherin (ECAD) protein expression has been linked to
      aggressive head and neck squamous cell carcinoma (HNSCC). Promoter
      hypermethylation of the cadherin 1, type 1 (CDH1) gene (encoding ECAD) is 1
      mechanism by which this protein can be inactivated, although this epigenetic
      alteration of the gene has not been linked conclusively to poorer patient outcome
      and, in fact, may be associated with better patient prognosis. METHODS: The
      authors investigated the prevalence of CDH1 promoter hypermethylation in a
      population-based case series of 340 primary HNSCC tumors using methylation
      specific polymerase chain reaction. They also studied the association between
      CDH1 hypermethylation and patient demographic characteristics using multivariate
      analysis and examined the impact of CDH1 hypermethylation on patient survival
      using both univariate and multivariate methods. RESULTS: Hypermethylation of CDH1
      was significantly more prevalent (P < .03) among individuals with a low smoking
      history independent of whether they were seropositive for human papillomavirus
      type 16 (HPV-16). Patients who had tumors with CDH1 hypermethylation had
      significantly better overall survival compared with patients who had tumors
      without hypermethylation (P < .02; log-rank test). This effect was independent of
      HPV-16 status and demonstrated a significant hazard ratio of 0.5 (95% confidence
      interval, 0.3-0.9) in a model that controlled for HPV-16 serology, age, sex, and
      tumor stage. CONCLUSIONS: The current results suggested that hypermethylation of
      CDH1 occurs more commonly in patients with HNSCC who are low smokers, suggesting
      that an additional factor may be driving this epigenetic alteration. Clinically,
      CDH1 hypermethylation may hold powerful prognostic potential in addition to that
      observed with HPV serology, and the authors concluded that it should be pursued
      in additional studies.

PMID- 18711703
TI  - 'Yours is potentially serious but most of these are cured': optimistic
      communication in UK outpatient oncology consultations.
AB  - OBJECTIVE: To describe how experienced doctors discuss radiotherapy and
      chemotherapy with cancer patients about to undergo such treatment. METHODS:
      Qualitative analysis of 27 consultations( )between consultant oncologists and
      patients with breast, head, and neck cancer or gastrointestinal cancer. Set in
      outpatient oncology clinics: one in the South West, one in the Midlands, and a
      large London teaching hospital. Participants included three experienced
      consultant oncologists and 27 patients diagnosed with cancer attending outpatient
      oncology consultations to discuss radiotherapy or chemotherapy. RESULTS: Doctors
      repeatedly invoked optimism when discussing bad and uncertain information about
      radiotherapy and chemotherapy. This was achieved by following relatively bad or
      uncertain information with some good information. Patients tended to collaborate
      in the construction of optimism. CONCLUSIONS: Doctors talked optimistically while
      sharing information about chemotherapy and radiotherapy with patients about to
      undergo such treatment. Research indicates that patients want their doctors to
      openly share bad and uncertain information, but to do so sensitively. Following
      uncertain or bad tidings with relatively better news was one way in which doctors
      delivered information honestly without diminishing opportunities for hope in the
      consultation room or optimism about the future. Findings from qualitative
      empirical studies, such as that described, provide a valuable educational adjunct
      to the role play and simulated patient interactions, often used in conventional
      communication skills training and research.

PMID- 18711704
TI  - Reye's and Reye's-like syndromes.
AB  - The review reports various questions about Reye's syndrome and Reye's-like
      syndromes. Although there is a significant decrease in the classic Reye's
      syndrome cases, because of the reduced employment of salicylates in children
      (salicylate seems to be the most important inducing factor of the syndrome in
      paediatric subjects affected by viral infection), the problem is still of
      interest considering the presence of different Reye's-like forms. All these
      pathological situations are associated with various aetiologic or predisposing
      causes that are examined in the text. Particular attention is placed on metabolic
      disorders, especially of fatty acid metabolism, and also of one amino acid. In
      fact, a latent form can also be the basis of possible biochemical disturbances
      induced by various exogenous factors such as viral infections, particularly of
      the respiratory tract (more rarely of bacterial aetiology), or produced by
      microbial toxins, or by chemical substances, including some therapeutic drugs. A
      full discussion of biochemical mechanisms of salicylate-induced Reye's syndrome
      is reported. Finally a possible diagnostic differentiation from classic Reye's
      syndrome and Reye's-like syndromes plus therapeutic prospects are briefly
      examined.

PMID- 18711705
TI  - Hospitalization for peptic ulcer and bleeding in users of selective COX-2
      inhibitors and nonselective NSAIDs with special reference to celecoxib.
AB  - PURPOSE: To assess the relative incidence of peptic ulcer bleeding and
      perforation (PUBP) in users of selective cyclooxygenase-2 (COX-2) inhibitors and
      nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: This was a
      retrospective case-control study based on insurance claims, with chart review to
      confirm cases. The base population consisted of 2.2 million adult users of
      celecoxib, diclofenac, ibuprofen, naproxen, rofecoxib, or valdecoxib who were
      covered by commercial health insurance in the United States from 1999-2003. For
      790 persons hospitalized for PUBP and 7887 controls, most recent NSAID/COX-2 use
      and a variety of medical and pharmacy risk factors were ascertained from the
      insurance files and analyzed by conditional logistic regression. The main outcome
      measure was the odds ratio (OR) associated with use of each drug by comparison to
      naproxen, and in successive intervals after last dispensing. RESULTS:
      Hospitalization for PUBP was highest from the date of NSAID/COX-2 dispensing
      through the end of an exposure period that corresponded to the days supply; the
      rate dropped steadily thereafter. The covariate-adjusted ORs by comparison to
      naproxen were: ibuprofen 0.86 (95% confidence interval (CI) 0.68, 1.09),
      rofecoxib 0.79 (0.62, 1.02), diclofenac 0.66 (0.47, 0.94), valdecoxib 0.50 (0.26,
      0.97), and celecoxib 0.45 (0.35, 0.58). The nonselective NSAIDs had an OR for
      PUBP of 1.51 (1.26, 1.98) compared to the selective COX-2 inhibitors. CONCLUSION:
      Nonselective NSAIDs convey half again as much risk of hospitalization for PUBP as
      do COX-2 inhibitors. Celecoxib users had about half the hospitalization rate of
      users of naproxen.

PMID- 18711706
TI  - Dynamics of cortical responses to tone pairs in relation to task difficulty: a
      MEG study.
AB  - We investigated the effect of task difficulty on the dynamics of auditory
      cortical responses. Whole-scalp magnetoencephalographic (MEG) signals were
      recorded while subjects performed a same/different frequency discrimination task
      on equiprobable tone pairs applied in blocks of five, which were separated by a
      10 s intertrial interval. Task difficulty was manipulated by the interpair
      frequency difference. The manipulation of task difficulty affected the amplitude
      of the N100m response to the first tone and the latency of the N100m response to
      the second tone in each pair. The N100m responses were smaller and peaked
      significantly later in the difficult than in the easy condition. The later
      processing field (PF) responses were longer in duration in the difficult
      condition. In both conditions, the duration of the PF response was negatively
      correlated with the subject's performance in the task, and was longer in the less
      successful subjects. The PF response may thus reflect the subjects' effort to
      resolve the task. The N100m and the PF responses did not differ between the tone
      pairs along the five-pair trial as a function of task difficulty, suggesting that
      changes in response along the five-pair trial are not easily affected by high
      level manipulations.

PMID- 18711707
TI  - Audiovisual integration during speech comprehension: an fMRI study comparing ROI
      based and whole brain analyses.
AB  - Visual information (lip movements) significantly contributes to speech
      comprehension raising the question for the neural implementation of audiovisual
      (AV) integration during speech processing. To replicate and extend earlier
      neuroimaging findings, we compared two different analysis approaches in a slow
      event-related fMRI study of healthy native speakers of German who were exposed to
      AV speech stimuli (disyllabic nouns) with audio and visual signals being either
      congruent or incongruent. First, data was subjected to whole brain general linear
      model analysis after transformation of all individual data sets into standard
      space. Second, a region of interest (ROI) approach based on individual anatomy
      was used with ROI defined in areas identified previously as being important for
      AV processing. Standard space analysis revealed a widespread cortical network
      including the posterior part of the left superior temporal sulcus, Broca's region
      and its right hemispheric counterpart showing increased activity for incongruent
      stimuli. The ROI approach allowed to identify differences in activity between
      Brodmann areas 44 and 45, within Broca's area for incongruent stimulation, and
      also allowed to study activity of subdivisions of superior temporal regions. The
      complementary strengths and weaknesses of the two analysis approaches are
      discussed.

PMID- 18711708
TI  - Working memory representation in atypical language dominance.
AB  - One of the most important factors controlling material specific processing in the
      human brain is language dominance, i.e. hemispheric specialization in semantic
      processes. Although previous studies have shown that lateralized long-term memory
      processes in the medial temporal lobes are modified in subjects with atypical
      (right) language dominance, the effect of language dominance on the neural basis
      of working memory (WM) has remained unknown. Here, we used functional MRI (fMRI)
      to study the impact of language dominance on the neural representation of WM. We
      conducted an n-back task in three different load conditions and with both verbal
      and nonverbal (spatial) material in matched groups of left and right language
      dominant subjects. This approach allowed us to investigate regions showing
      significant interactions between language dominance and material. Overall, right
      dominant subjects showed an increased inter-individual variability of WM-related
      activations. Verbal WM involved more pronounced activation of the left fusiform
      cortex in left dominant subjects and of the right inferior parietal lobule in the
      right dominant group. Spatial WM, on the other hand, induced activation of right
      hemispheric regions in left dominant subjects, but no specific activations in
      right dominant subjects. Taken together, these findings indicate that the neural
      basis of verbal WM processes depends on language dominance and is more mutable in
      right dominant subjects. The increased variability in right dominant subjects
      strongly suggests that a standard network of material-dependent WM processes
      exists in left dominant subjects, and that right dominant subjects use variable
      alternative networks.

PMID- 18711709
TI  - Decreased neural activity in reward circuitry during personal reference in
      abstinent alcoholics--a fMRI study.
AB  - Two of the most striking features in alcoholism are the irresistible craving for
      alcohol and the proceeding neglect of other activities and pleasures that were
      formerly relevant. Craving has been investigated extensively and is commonly due
      to a dysfunctional reward system. The neural basis of the neglect of self
      relevant interests, which can be described as altered personal reference, and its
      association to the reward system, however, remains unclear. Using fMRI, we
      investigated neural activity during a paradigm that tested for both reward and
      personal reference with regard to the same stimuli, i.e., alcoholic and
      nonalcoholic pictures, in healthy subjects and abstinent alcoholic patients.
      Alcoholic patients showed slightly reduced signal changes in the brain stem
      adjacent to ventral tegmental area (VTA) and in the ventromedial prefrontal
      cortex (VMPFC) during the reward task, while we found no alterations in the right
      and left ventral striatum (VS). The same regions (VS, VTA, and VMPFC), however,
      showed reduced signal changes during personal reference with lack of neural
      differentiation between high and low referenced stimuli in alcoholic patients. In
      summary, we demonstrate for the first time neurophysiological alterations in
      reward circuitry during personal reference in alcoholic patients. Our results
      underline the important role of the reward circuitry during personal reference in
      the pathophysiology of alcohol addiction.

PMID- 18711710
TI  - Attentional load modifies early activity in human primary visual cortex.
AB  - Recent theories of selective attention assume that the more attention is required
      by a task, the earlier are irrelevant stimuli filtered during perceptual
      processing. Previous functional MRI studies have demonstrated that primary visual
      cortex (V1) activation by peripheral distractors is reduced by higher task
      difficulty at fixation, but it remains unknown whether such changes affect
      initial processing in V1 or subsequent feedback. Here we manipulated attentional
      load at fixation while recording peripheral visual responses with high-density
      EEG in 28 healthy volunteers, which allowed us to track the exact time course of
      attention-related effects on V1. Our results show a modulation of the earliest
      component of the visual evoked potential (C1) as a function of attentional load.
      Additional topographic and source localization analyses corroborated this
      finding, with significant load-related differences observed throughout the first
      100 ms post-stimulus. However, this effect was observed only when stimuli were
      presented in the upper visual field (VF), but not for symmetrical positions in
      the lower VF. Our findings demonstrate early filtering of irrelevant information
      under increased attentional demands, thus supporting models that assume a
      flexible mechanism of attentional selection, but reveal important functional
      asymmetries across the VF.

PMID- 18711712
TI  - But what if ...

PMID- 18711711
TI  - Stability of tactile- and pain-related fMRI brain activations: an examination of
      threshold-dependent and threshold-independent methods.
AB  - Functional MRI can be used to assess brain plasticity over time. To confidently
      attribute changes in activation patterns to cortical plasticity, it is important
      to establish the stability of cortical activation patterns. Because little is
      known concerning the stability of somatosensory-evoked brain responses, we
      assessed the reproducibility of within-subject responses in key somatosensory
      regions [thalamus, primary and secondary cortex (S1, S2)] to tactile and painful
      stimuli using threshold-dependent and threshold-independent analyses. Six
      subjects underwent four biweekly scanning sessions during which tactile and
      painful stimuli were applied to the hand. Standard thresholding and voxel
      counting techniques were compared with a novel threshold-independent method
      utilizing percent signal change within the regions of interest. Contralateral S1
      and S2 were qualitatively reproducible during tactile stimulation, with
      overlapping activations >85% of the time. S2 was also highly reproducible during
      painful stimulation (88%), whereas S1 was less reproducible (44%). However,
      activation in the thalamus to both tactile and painful stimulation was highly
      variable. Ipsilateral activation was consistent within S2 but sparse within S1
      and thalamus. Deactivations within ipsilateral S1 occurred 48% of the time with
      tactile stimuli, and 90% of the time with painful stimuli. Within contralaterally
      activated regions intraclass correlations (ICCs) were very high using the
      unthresholded method regardless of the type of stimulation, whereas much lower
      ICCs arose from the thresholded analyses. These data indicate that a threshold
      independent analysis can produce more reproducible outcomes than a standard
      threshold-dependent analysis.

PMID- 18711713
TI  - The fault is not in her parents but in her insula--a neurobiological hypothesis
      of anorexia nervosa.
AB  - The reported abnormalities of brain function in anorexia nervosa (AN) include
      impairment of neural circuits involving cortical (orbito-frontal, somatosensory
      and parietal) and sub-cortical (amygdala, hippocampus, thalamus, hypothalamus and
      striatum) structures. The insular cortex serves an integrative function for all
      the structures relevant to the features of AN and as such may be central to this
      impairment. We hypothesise that a rate limiting dysfunction of neural circuitry
      integrated by the insula can account for the clinical phenomena of AN. Such
      dysfunction could account for the known psychopathology, neuroimaging
      abnormalities and neuropsychological deficits. Proposals to test this hypothesis
      are made.

PMID- 18711715
TI  - MSINDO study of acid promoted dissolution of planar MgO and NiO surfaces.
AB  - Despite the structural similarity, MgO is fast dissolving in low pH solution,
      whereas NiO is slow dissolving under the same conditions. In addition, the planar
      MgO (100) surface immediately reconstructs to form pits and protrusions, whereas
      this behavior has not been observed with NiO (100). Our previous study, using the
      semiempirical self-consistent field molecular orbital (SCFMO) method MSINDO
      showed that it was possible for MgO dissolution but not NiO dissolution to occur
      via the migration of a metal-oxygen pair to an ex situ position. However, we have
      now found a more energetically favorable and realistic dissolution mechanism
      involving the dissociation of a water molecule (adsorbed on a metal site) prior
      to migration. Products from this dissociation (H and OH) weaken adjacent metal
      oxygen bonds. Dissociation of a second adsorbed water molecule is required to
      complete the process. For both oxides, the energy barrier determined from the
      energy profile of the metal-oxygen pair migration was found to be lower than the
      activation energy of water dissociation at the planar surface as reported in
      previous study. This would suggest that the dissociation of water molecules at
      the planar surface is rate-determining in the surface restructuring step of
      dissolution. It was demonstrated that surface restructuring and dissolution of
      MgO is possible whereas highly improbable for NiO, in agreement with experimental
      observations.

PMID- 18711716
TI  - Implementation of dynamical nucleation theory with quantum potentials.
AB  - A method is implemented within the context of dynamical nucleation theory in
      order to efficiently determine the ab initio water dimer evaporation rate
      constant. The drive for increased efficiency in a Monte Carlo methodology is
      established by the need to use relatively expensive quantum mechanical
      interaction potentials. A discussion is presented illustrating the theory,
      algorithm, and implementation of this method to the water dimer. Hartree-Fock and
      second order Moller-Plesset perturbation theories along with the Dang-Chang
      polarizable classical potential are utilized to determine the ab initio water
      dimer evaporation rate constant.

PMID- 18711717
TI  - Comparison of some representative density functional theory and wave function
      theory methods for the studies of amino acids.
AB  - Energies of different conformers of 22 amino acid molecules and their protonated
      and deprotonated species were calculated by some density functional theory (DFT;
      SVWN, B3LYP, B3PW91, MPWB1K, BHandHLYP) and wave function theory (WFT; HF, MP2)
      methods with the 6-311++G(d,p) basis set to obtain the relative conformer
      energies, vertical electron detachment energies, deprotonation energies, and
      proton affinities. Taking the CCSD/6-311++G(d,p) results as the references, the
      performances of the tested DFT and WFT methods for amino acids with various
      intramolecular hydrogen bonds were determined. The BHandHLYP method was the best
      overall performer among the tested DFT methods, and its accuracy was even better
      than that of the more expensive MP2 method. The computational dependencies of the
      five DFT methods and the HF and MP2 methods on the basis sets were further
      examined with the 6-31G(d,p), 6-311++G(d,p), aug-cc-pVDZ, 6-311++G(2df,p), and
      aug-cc-pVTZ basis sets. The differences between the small and large basis set
      results have decreased quickly for the hybrid generalized gradient approximation
      (GGA) methods. The basis set convergence of the MP2 results has been, however,
      very slow. Considering both the cost and the accuracy, the BHandHLYP functional
      with the 6-311++G(d,p) basis set is the best choice for the amino acid systems
      that are rich in hydrogen bonds.

PMID- 18711718
TI  - Conformational selection of protein kinase A revealed by flexible-ligand flexible
      protein docking.
AB  - Protein kinases have high structural plasticity: their structure can change
      significantly, depending on what ligands are bound to them. Rigid-protein docking
      methods are not capable of describing such effects. Here, we present a new
      flexible-ligand flexible-protein docking model in which the protein can adopt
      conformations between two extremes observed experimentally. The model utilized a
      molecular dynamics-based simulated annealing cycling protocol and a distance
      dependent dielectric model to perform docking. By testing this model on docking
      four diverse ligands to protein kinase A, we found that the ligands were able to
      dock successfully to the protein with the proper conformations of the protein
      induced. By imposing relatively soft conformational restraints to the protein
      during docking, this model reduced computational costs yet permitted essential
      conformational changes that were essential for these inhibitors to dock properly
      to the protein. For example, without adequate movement of the glycine-rich loop,
      it was difficult for the ligands to move from the surface of the protein to the
      binding site. In addition, these simulations called for better ways to compare
      simulation results with experiment other than using the popular root-mean-square
      deviation between the structure of a ligand in a docking pose and that in
      experiment because the structure of the protein also changed. In this work, we
      also calculated the correlation coefficient between protein-ligand/protein
      protein distances in the docking structure and those in the crystal structure to
      check how well a ligand docked into the binding site of the protein and whether
      the proper conformation of the protein was induced.

PMID- 18711719
TI  - Strategies to model the near-solute solvent molecular density/polarization.
AB  - The solvent molecular distribution significantly affects the behavior of the
      solute molecules and is thus important in studying many biological phenomena. It
      can be described by the solvent molecular density distribution, g, and the
      solvent electric dipole distribution, p. The g and p can be computed directly by
      counting the number of solvent molecules/dipoles in a microscopic volume centered
      at r during a simulation or indirectly from the mean force F and electrostatic
      field E acting on the solvent molecule at r, respectively. However, it is not
      clear how the g and p derived from simulations depend on the solvent molecular
      center or the solute charge and if the g(F) and p(E) computed from the mean force
      and electric field acting on the solvent molecule, respectively, could reproduce
      the corresponding g and p obtained by direct counting. Hence, we have computed g,
      p, g(F), and p(E) using different water centers from simulations of a solute atom
      of varying charge solvated in TIP3P water. The results show that g(F) and p(E)
      can reproduce the g and p obtained using a given count center. This implies that
      rather than solving the coordinates of each water molecule by MD simulations, the
      distribution of water molecules could be indirectly obtained from analytical
      formulas for the mean force F and electrostatic field E acting on the solvent
      molecule at r. Furthermore, the dependence of the g and p distributions on the
      solute charge revealed provides an estimate of the change in g and p surrounding
      a biomolecule upon a change in its conformation.

PMID- 18711720
TI  - MeTA studio: a cross platform, programmable IDE for computational chemist.
AB  - The development of a cross-platform, programmable integrated development
      environment (IDE), MeTA Studio, specifically tailored but not restricted to
      computational chemists working in the area of quantum chemistry with an emphasis
      on handling large molecules is presented. The IDE consists of a number of modules
      which include a visualizer and a programming and collaborative framework. The
      inbuilt viewer assists in visualizing molecules, their scalar fields, manually
      fragmenting a molecule, and introduces some innovative but simple techniques for
      handling large molecules. These include a simple Find language and simultaneous
      multiple camera views of the molecule. Basic tools needed to handle collaborative
      computing effectively are also included opening up new vistas for sharing ideas
      and information among computational chemists working on similar problems. MeTA
      Studio is an integrated programming environment that provides a rich set of
      application programming interfaces (APIs) which can be used to easily extend its
      functionality or build new applications as needed by the users.
      (http://code.google.com/p/metastudio/).

PMID- 18711721
TI  - Toward accurate relative energy predictions of the bioactive conformation of
      drugs.
AB  - Quantifying the relative energy of a ligand in its target-bound state (i.e. the
      bioactive conformation) is essential to understand the process of molecular
      recognition, to optimize the potency of bioactive molecules and to increase the
      accuracy of structure-based drug design methods. This is, nevertheless, seriously
      hampered by two interrelated issues, namely the difficulty in carrying out an
      exhaustive sampling of the conformational space and the shortcomings of the
      energy functions, usually based on parametric methods of limited accuracy.
      Matters are further complicated by the experimental uncertainty on the atomic
      coordinates, which precludes a univocal definition of the bioactive conformation.
      In this article we investigate the relative energy of bioactive conformations
      introducing two major improvements over previous studies: the use sophisticated
      QM-based methods to take into account both the internal energy of the ligand and
      the solvation effect, and the application of physically meaningful constraints to
      refine the bioactive conformation. On a set of 99 drug-like molecules, we find
      that, contrary to previous observations, two thirds of bioactive conformations
      lie within 0.5 kcal mol(-1) of a local minimum, with penalties above 2.0 kcal
      mol(-1) being generally attributable to structural determination inaccuracies.
      The methodology herein described opens the door to obtain quantitative estimates
      of the energy of bioactive conformations and can be used both as an aid in
      refining crystallographic structures and as a tool in drug discovery.

PMID- 18711722
TI  - Identification of amyloidogenic peptide sequences using a coarse-grained
      physicochemical model.
AB  - Cross-beta amyloid is implicated in over 20 human diseases. Experiments suggest
      that specific sequence elements within amyloidogenic proteins play a major role
      in seeding amyloid formation. Identifying these seeding sequences is important
      for rationalizing the molecular mechanisms of amyloid formation and for
      elaborating therapeutic strategies that target amyloid. Theoretical techniques
      play an important role in facilitating the identification and structural
      characterization of putative seeding sequences; most amyloid species are not
      amenable to high resolution experimental structure techniques. In this study we
      have combined a coarse-grained physicochemical protein model with a highly
      efficient Monte Carlo sampling technique to identify amyloidogenic sequences in
      four proteins for which respective experimental peptide fragmentation data exist.
      Peptide sequences were defined as amyloidogenic if the ensemble structure
      predicted for three interacting peptides described a stable and regular three
      stranded beta-sheet. For such peptides, free energies were calculated to provide
      a measure of amyloid propensity. The overall agreement between the experimental
      and predicted data is good, and we correctly identify several self-recognition
      motifs proposed to define the cross-beta amyloid fibril architectures of two of
      the proteins. Our results compare very favorably with those obtained using
      atomistic molecular dynamics methods, though our simulations are 30-40 times
      faster.

PMID- 18711723
TI  - Understanding the ring current effects on magnetic shielding of hydrogen and
      carbon nuclei in naphthalene and anthracene.
AB  - The local response to an external magnetic field normal to the molecular plane of
      naphthalene and anthracene was investigated via current density and magnetic
      shielding density maps. The Biot-Savart law shows that the deshielding caused by
      pi-ring currents in naphthalene is stronger for alpha- than for beta-protons due
      to geometrical factors. The shielding tensor of the carbon nuclei in both
      molecules is strongly anisotropic and its out-of-plane component determines the
      up-field chemical shift of (13)C in nuclear magnetic resonance spectra. The pi
      ring currents flowing beyond the C-skeleton in front of a probe carbon nucleus,
      and on remote parts of the molecular perimeter, yield positive contributions to
      the out-of-plane component of carbon shielding as big as approximately 10-15% of
      the total values. Near Hartree-Fock estimates of magnetizability and magnetic
      shielding at the nuclei fully consistent with the current model are reported.

PMID- 18711724
TI  - DnaJB6 is present in the core of Lewy bodies and is highly up-regulated in
      parkinsonian astrocytes.
AB  - DnaJ/Hsp40 chaperones determine the activity of Hsp70s by stabilizing their
      interaction with substrate proteins. We have predicted, based on the in silico
      analysis of a brain-derived whole-genome transcriptome data set, an increased
      expression of DnaJ/Hsp40 homologue, subfamily B, member 6 (DnaJB6) in Parkinson's
      disease (PD; Moran et al. [2006] Neurogenetics 7:1-11). We now show that DnaJB6
      is a novel component of Lewy bodies (LBs) in both PD substantia nigra and PD
      cortex and that it is strongly up-regulated in parkinsonian astrocytes. The
      presence of DnaJB6 in the center of LBs suggests an early and direct involvement
      of this chaperone in the neuronal disease process associated with PD. The strong
      concomitant expression of DnaJB6 in astrocytes emphasizes the involvement of
      glial cells in PD and could indicate a route for therapeutic intervention.
      Extracellular alpha-synuclein originating from intravesicular alpha-synuclein is
      prone to aggregation and the potential source of extracellular aggregates (Lee
      [2008] J. Mol. Neurosci. 34:17-22). The observed strong expression of DnaJB6 by
      astrocytes could reflect a protective reaction, so reducing the neuronal release
      of toxic alpha-synuclein and supporting the astrocyte response in PD might limit
      the progression of the disease process.

PMID- 18711725
TI  - Lysophosphatidylcholine protects cerebellar granule neurons from apoptotic cell
      death.
AB  - Cultured cerebellar granule neurons (CGNs) undergo apoptosis when deprived of
      depolarizing stimulation and provide an in vitro model system with which to study
      the effects of neurotrophic substances. Our previous results showed that
      secretory phospholipases A(2) (sPLA(2)s) protect CGNs from apoptotic cell death
      under the nondepolarizing condition. In this study, we further analyzed the
      mechanism whereby sPLA(2) exhibits this effect. Among the primary metabolites of
      sPLA(2) tested, lysophosphatidylcholine (LPC), but not other lysophospholipids,
      remarkably rescued CGNs from apoptosis. In contrast, neither arachidonic nor
      oleic acids displayed neurotrophic effect. Release of LPC into the culture media
      occurred in response to sPLA(2) treatment, and degradation or sequestration of
      LPC attenuated the survival-promoting effects of sPLA(2) and LPC. The
      neurotrophic effect of LPC required the presence of extracellular Ca(2+) and L
      type Ca(2+) channel activity, suggesting that Ca(2+) influx across the plasma
      membrane is evoked by LPC. sPLA(2)- or LPC-induced promotion of CGN survival was
      suppressed by inhibitors of protein kinase A and phospholipase C, suggesting that
      they play a role in mediating survival-promoting signal of sPLA(2). The results
      presented here demonstrate a novel, unexpected neurotrophin-like effect of LPC in
      the central nervous system.

PMID- 18711726
TI  - Specific interaction between Sam68 and neuronal mRNAs: implication for the
      activity-dependent biosynthesis of elongation factor eEF1A.
AB  - In cultured hippocampal neurons and in adult brain, the splicing regulatory
      protein Sam68 is partially relocated to the somatodendritic domain and associates
      with dendritic polysomes. Transfer to the dendrites is activity-dependent. We
      have investigated the repertoire of neuronal mRNAs to which Sam68 binds in vivo.
      By using coimmunoprecipitation and microarray screening techniques, Sam68 was
      found to associate with a number of plasticity-related mRNA species, including
      Eef1a1, an activity-responsive mRNA coding for translation elongation factor
      eEF1A. In cortical neuronal cultures, translation of the Eef1a1 mRNA was strongly
      induced by neuronal depolarisation and correlated with enhanced association of
      Sam68 with polysomal mRNAs. The possible function of Sam68 in Eef1a1 mRNA
      utilization was studied by expressing a dominant-negative, cytoplasmic Sam68
      mutant (GFP-Sam68DeltaC) in cultured hippocampal neurons. The level of eEF1A was
      lower in neurons expressing GFP-Sam68DeltaC than in control neurons, supporting
      the proposal that endogenous Sam68 may contribute to the translational efficiency
      of the Eef1a1 mRNA. These findings are discussed in the light of the complex,
      potentially crucial regulation of eEF1A biosynthesis during long-term synaptic
      change.

PMID- 18711727
TI  - Effects of maternal antenatal glucocorticoid treatment on apoptosis in the ovine
      fetal cerebral cortex.
AB  - We examined the effects of single and multiple maternal glucocorticoid courses on
      apoptosis in the cerebral cortices of ovine fetuses (CC). Ewes received single
      dexamethasone or placebo courses at 104-106 or 133-135 days or multiple courses
      between 76-78 and 104-106 days gestation. In the single-course groups, ewes
      received four 6 mg dexamethasone or placebo injections every 12 hr for 48 hr.
      Multiple-course groups received the same treatment once per week for 5 weeks.
      Neuronal and nonneuronal apoptotic cell numbers per square millimeter were
      determined with TUNEL and NeuN staining and with caspase-3 enzyme activity on CC
      tissues harvested at 106-108 (70%) or 135-137 (90%) days of gestation. Apoptotic
      cell numbers and caspase-3 activity were 50% lower (P < 0.02) after single
      placebo courses at 90% than 70% gestation; 90% of apoptotic cells were (P < 0.01)
      nonneuronal at both ages. Nonneuronal apoptotic cells and caspase-3 activity were
      40% and 20% lower (P < 0.02) after single dexamethasone than placebo courses at
      70%, but not 90%, gestation. Caspase-3 activity was 20% lower (P < 0.01) after
      multiple dexamethasone than placebo courses, but apoptotic cell number did not
      differ. We conclude that nonneuronal apoptosis represents the major form of
      apoptosis in the CC at both 70% and 90% of gestation. Apoptosis in nonneuronal
      cells decreases with maturity and after a single course of dexamethasone at 70%,
      but not at 90%, gestation and not after multiple courses at 70% gestation. We
      speculate that a single course of glucocorticoids exerts maturational changes on
      the rate of apoptosis in the cerebral cortex of preterm ovine fetuses.

PMID- 18711729
TI  - Technical note: standardized and semiautomated Harris lines detection.
AB  - Arrest in long bone growth and the subsequent resumption of growth may be visible
      as radiopaque transverse lines in radiographs (Harris lines, HL; Harris, HA.
      1933. Bone growth in health and disease. London: Oxford University Press). The
      assessment of individual age at occurrence of such lines, as part of
      paleopathological skeletal studies, is time-consuming and shows large intra- and
      interobserver variability. Thus, a standardized, automated detection algorithm
      would help to increase the validity of such paleopathological research. We
      present an image analysis application facilitating automatic detection of HL. On
      the basis of established age calculation methods, the individual age-at-formation
      can be automatically assessed with the tool presented. Additional user input to
      confirm the automatic result is possible via an intuitive graphical user
      interface. Automated detection of HL from digital radiographs of a sample of late
      Medieval Swiss tibiae was compared to the consensus of manual assessment by two
      blinded expert observers. The intra- and interobserver variability was high. The
      quality of the observer result improved when standardized detection criteria were
      defined and applied. The newly developed algorithm detected two-thirds of the HL
      that were identified as consensus lines between the observers. It was, however,
      necessary to validate the last one-third by manual editing. The lack of a large
      test series must be noted. The application is freely available for further
      testing by any interested researcher.

PMID- 18711728
TI  - Effects of neuroglobin overexpression on mitochondrial function and oxidative
      stress following hypoxia/reoxygenation in cultured neurons.
AB  - Neuroglobin (Ngb) is a recently discovered tissue globin with a high affinity for
      oxygen that is widely and specifically expressed in neurons of vertebrate central
      and peripheral nervous systems. Our laboratory and others have shown Ngb
      overexpression can protect neurons against hypoxic/ischemic insults, but the
      underlying mechanisms remain poorly understood. In this study, we examined the
      effects of Ngb overexpression on mitochondrial function, oxidative stress, and
      neurotoxicity in primary cortical neurons following hypoxia/reoxygenation (H/R).
      Ngb-overexpressing transgenic neurons (Ngb-Tg) were significantly protected
      against H/R-induced cell death. Rates of decline in ATP levels, MTT reduction,
      and mitochondrial membrane potential were significantly ameliorated in Ngb-Tg
      neurons. Furthermore, Ngb overexpression reduced superoxide anion generation
      after H/R, whereas glutathione levels were significantly improved compared with
      WT controls. Taken together, these data suggest that Ngb is neuroprotective
      against hypoxia, in part by improving mitochondria function and decreasing
      oxidative stress.

PMID- 18711730
TI  - Is Central Asia the eastern outpost of the Neandertal range? A reassessment of
      the Teshik-Tash child.
AB  - Since its discovery in southeastern Uzbekistan in 1938, the Teshik-Tash child has
      been considered a Neandertal. Its affinity is important to studies of Late
      Pleistocene hominin growth and development as well as interpretations of the
      Central Asian Middle Paleolithic and the geographic distribution of Neandertals.
      A close examination of the original Russian monograph reveals the incompleteness
      of key morphologies associated with the cranial base and face and problems with
      the reconstruction of the Teshik-Tash cranium, making its Neandertal attribution
      less certain than previously assumed. This study reassesses the Neandertal status
      of Teshik-Tash 1 by comparing it to a sample of Neandertal, Middle and Upper
      Paleolithic modern humans, and recent human sub-adults. Separate examinations of
      the cranium and mandible are conducted using multinomial logistic regression and
      discriminant function analysis to assess group membership. Results of the cranial
      analysis group Teshik-Tash with Upper Paleolithic modern humans when variables
      are not size-standardized, while results of the mandibular analysis place the
      specimen with recent modern humans for both raw and size-standardized data.
      Although these results are influenced by limitations related to the incomplete
      nature of the comparative sample, they suggest that the morphology of Teshik-Tash
      1 as expressed in craniometrics is equivocal. Although, further quantitative
      studies as well as additional sub-adult fossil finds from this region are needed
      to ascertain the morphological pattern of this specimen specifically, and Central
      Asian Middle Paleolithic hominins in general, these results challenge current
      characterizations of this territory as the eastern boundary of the Neandertal
      range during the Late Pleistocene.

PMID- 18711731
TI  - Under restrictive conditions, can the widths of linear enamel hypoplasias be used
      as relative indicators of stress episode duration?
AB  - Linear enamel hypoplasia (LEH), a type of enamel defect reflecting nonspecific
      physiological stress, has traditionally been used by bioarchaeologists to assess
      human health. Initially, measurements of defect width were used to estimate the
      duration of stress episodes. More recently, methods of counting within-defect
      perikymata (enamel growth increments) were developed to more accurately assess
      duration. Because perikymata are often not continuously visible within defects,
      while widths can usually be measured, the primary purpose of this article was to
      determine if, under restrictive conditions, the widths of LEH defects might be
      used as relative indicators of stress episode duration. Using a set of dental
      replicas from the prehistoric Irene Mound (1150-1400 A.D.), this study also
      investigated potential sources of variation in defect widths and how often defect
      widths could be measured and within-defect perikymata counted. Of 120 defects,
      only 47 contained both measurable defect widths and total within-defect
      perikymata, while 79 had measurable defect widths. Regression analysis revealed
      that, for these 47 defects, defect widths were more strongly related to the total
      number of within-defect perikymata than they were to crown region or tooth type.
      Although wide prediction intervals indicated that a defect's width could not be
      used to predict the number of within-defect perikymata for an individual,
      narrower confidence intervals associated with hypothetical mean population widths
      suggested that mean defect widths might be used to rank populations in terms of
      relative average stress episode duration.

PMID- 18711732
TI  - Temporal variation and interaction between nutritional and developmental
      instability in prehistoric Japanese populations.
AB  - We examined nutritional and developmental instability in prehistoric Japan, using
      data from 49 individuals across 13 archaeological sites. Hypoplasia incidence was
      used as a measure of nutritional stress, and fluctuating asymmetry (of upper
      facial breath, orbital breadth, and orbital height) as an indirect assessment of
      developmental instability. Abundant resources due to a stable climate during the
      Middle Jomon (5,000-3,000 BP) encouraged population growth, which led to regional
      cultural homogeneity and complexity. A population crash on Honshu in the
      Late/Final Jomon (roughly 4,000-2,000 BP) led to regionally divergent subsistence
      economies and settlement patterns. We find that the nutritional stress was
      consistent between periods, but developmental instability (DI) decreased in the
      Late/Final Jomon. While the DI values were not statistically significant, the
      higher values for Middle Jomon may result from sedentism, social stratification,
      and differential access to resources. On Hokkaido, Jomon culture persisted until
      the Okhotsk period (1,000-600 BP), marked by the arrival of immigrants from
      Sakhalin. Nutritional stress was consistent between Middle and Late/Final Jomon,
      but DI increased in the Late/Final. Nutritional and developmental instability
      decreased from Late/Final to Okhotsk, suggesting a positive immigrant effect. We
      expected to find an association between stress markers due to the synergistic
      relationship between nutrition and pathology. The data support this hypothesis,
      but only one finding was statistically significant. While high critical values
      from small sample sizes place limits on the significance of our results, we find
      that the impact of environmental and cultural change to prehistoric Japanese
      populations was minimal.

PMID- 18711733
TI  - Relative limb strength and locomotion in Homo habilis.
AB  - The Homo habilis OH 62 partial skeleton has played an important, although
      controversial role in interpretations of early Homo locomotor behavior. Past
      interpretive problems stemmed from uncertain bone length estimates and
      comparisons using external bone breadth proportions, which do not clearly
      distinguish between modern humans and apes. Here, true cross-sectional bone
      strength measurements of the OH 62 femur and humerus are compared with those of
      modern humans and chimpanzees, as well as two early H. erectus specimens-KNM-WT
      15000 and KNM-ER 1808. The comparative sections include two locations in the
      femur and two in the humerus in order to encompass the range of possible section
      positions in the OH 62 specimens. For each combination of section locations,
      femoral to humeral strength proportions of OH 62 fall below the 95% confidence
      interval of modern humans, and for most comparisons, within the 95% confidence
      interval of chimpanzees. In contrast, the two H. erectus specimens both fall
      within or even above the modern human distributions. This indicates that load
      distribution between the limbs, and by implication, locomotor behavior, was
      significantly different in H. habilis from that of H. erectus and modern humans.
      When considered with other postcranial evidence, the most likely interpretation
      is that H. habilis, although bipedal when terrestrial, still engaged in frequent
      arboreal behavior, while H. erectus was a completely committed terrestrial biped.
      This adds to the evidence that H. habilis (sensu stricto) and H. erectus
      represent ecologically distinct, parallel lineages during the early Pleistocene.

PMID- 18711734
TI  - Rhesus macaque milk: magnitude, sources, and consequences of individual variation
      over lactation.
AB  - Lactation represents the greatest postnatal energetic expenditure for mammalian
      mothers, and a mother's ability to sustain the costs of lactation is influenced
      by her physical condition. Mothers in good condition may produce infants who
      weigh more, grow faster, and are more likely to survive than the infants of
      mothers in poor condition. These effects may be partially mediated through the
      quantity and quality of milk that mothers produce during lactation. However, we
      know relatively little about the relationships between maternal condition, milk
      composition, milk yield, and infant outcomes. Here, we present the first
      systematic investigation of the magnitude, sources, and consequences of
      individual variation in milk for an Old World monkey. Rhesus macaques produce
      dilute milk typical of the primate order, but there was substantial variation
      among mothers in the composition and amount of milk they produced and thus in the
      milk energy available to infants. Relative milk yield value (MYV), the grams of
      milk obtained by mammary evacuation after 3.5-4 h of maternal-infant separation,
      increased with maternal parity and was positively associated with infant weight.
      Both milk gross energy (GE) and MYV increased during lactation as infants aged.
      There was, however, a trade-off; those mothers with greater increases in GE had
      smaller increases in MYV, and their infants grew more slowly. These results from
      a well-fed captive population demonstrate that differences between mothers can
      have important implications for milk synthesis and infant outcome.

PMID- 18711735
TI  - Allometry of facial mobility in anthropoid primates: implications for the
      evolution of facial expression.
AB  - Body size may be an important factor influencing the evolution of facial
      expression in anthropoid primates due to allometric constraints on the perception
      of facial movements. Given this hypothesis, I tested the prediction that observed
      facial mobility is positively correlated with body size in a comparative sample
      of nonhuman anthropoids. Facial mobility, or the variety of facial movements a
      species can produce, was estimated using a novel application of the Facial Action
      Coding System (FACS). I used FACS to estimate facial mobility in 12 nonhuman
      anthropoid species, based on video recordings of facial activity in zoo animals.
      Body mass data were taken from the literature. I used phylogenetic generalized
      least squares (PGLS) to perform a multiple regression analysis with facial
      mobility as the dependent variable and two independent variables: log body mass
      and dummy-coded infraorder. Together, body mass and infraorder explain 92% of the
      variance in facial mobility. However, the partial effect of body mass is much
      stronger than for infraorder. The results of my study suggest that allometry is
      an important constraint on the evolution of facial mobility, which may limit the
      complexity of facial expression in smaller species. More work is needed to
      clarify the perceptual bases of this allometric pattern.

PMID- 18711736
TI  - mtDNA and Y-chromosome variation in the Talysh of Iran and Azerbaijan.
AB  - The Northern Talysh from Azerbaijan and the Southern Talysh from Iran self
      identify as one ethnic group and speak a Northwestern Iranian language. However,
      the Northern and Southern Talysh dialects are so different that they may actually
      be separate languages. Does this linguistic differentiation reflect internal
      change due to isolation, or could contact-induced change have played a role? We
      analyzed mtDNA HVI sequences, 11 Y-chromosome bi-allelic markers, and 9 Y-STR
      loci in Northern and Southern Talysh and compared them with their neighboring
      groups. The mtDNA data show a close relatedness of both groups with each other
      and with neighboring groups, whereas the Northern Talysh Y-chromosome variation
      differs from that of neighboring groups, probably as a result of genetic drift.
      This genetic drift most likely reflects a founder event in the male gene pool of
      Northern Talysh: either fewer males than females migrated to Azerbaijan, or there
      was a higher degree of relatedness among the male migrants. Since we find no
      evidence of substantial genetic contact between either Northern or Southern
      Talysh and neighboring groups, we conclude that internal change, rather than
      contact-induced change, most likely explains the linguistic differentiation
      between Northern and Southern Talysh.

PMID- 18711737
TI  - Brief communication: dental development and enamel thickness in the Lakonis
      Neanderthal molar.
AB  - Developmental and structural affinities between modern human and Neanderthal
      dental remains continue to be a subject of debate as well as their utility for
      informing assessments of life history and taxonomy. Excavation of the Middle
      Paleolithic cave site Lakonis in southern Greece has yielded a lower third molar
      (LKH 1). Here, we detail the crown development and enamel thickness of the distal
      cusps of the LKH 1 specimen, which has been classified as a Neanderthal based on
      the presence of an anterior fovea and mid-trigonid crest. Crown formation was
      determined using standard histological techniques, and enamel thickness was
      measured from a virtual plane of section. Developmental differences include
      thinner cuspal enamel and a lower periodicity than modern humans. Crown formation
      in the LKH 1 hypoconid is estimated to be 2.6-2.7 years, which is shorter than
      modern human times. The LKH 1 hypoconid also shows a more rapid overall crown
      extension rate than modern humans. Relative enamel thickness was approximately
      half that of a modern human sample mean; enamel on the distal cusps of modern
      human third molars is extremely thick in absolute and relative terms. These
      findings are consistent with recent studies that demonstrate differences in crown
      development, tissue proportions, and enamel thickness between Neanderthals and
      modern humans. Although overlap in some developmental variables may be found, the
      results of this and other studies suggest that Neanderthal molars formed in
      shorter periods of time than modern humans, due in part to thinner enamel and
      faster crown extension rates.

PMID- 18711738
TI  - Growth in colony living anubis baboon infants and its relationship with maternal
      activity budgets and reproductive status.
AB  - Early growth is of interest because it is susceptible to maternal effects and
      linked to fitness components for a range of species. Here we present
      anthropometric measurements on 23 infant olive baboons born into a captive colony
      in order to describe growth over the first 2 years of life, to explore maternal
      influences on growth, and to assess the impact of growth profiles on maternal
      reproduction. Six main findings emerged: 1) Infant growth rates in our colony
      were higher than those reported for wild populations but comparable to those
      observed for food-enhanced animals. 2) The ratio of infant mass to maternal mass
      was positively associated with reproductive parameters, such as duration of post
      partum amenorrhea and interbirth interval. 3) Mothers resumed cycling and
      reconceived when their infants attained a relatively consistent threshold mass.
      4) Infant mass-for-age was associated with maternal rank and, independently, with
      maternal mass such that females of high dominance rank and heavy females had
      relatively large infants at their resumption of cycling. 5) Low-ranking and
      lighter females had longer investment periods but smaller infants. They continued
      investment in infant through prolonged lactation until their infants reached a
      mass similar to that of infants of high-ranking/heavy mothers, suggesting that
      the lengthening of investment is essentially compensatory for slow early growth.
      6) There was no relationship between infant growth and maternal activity budgets.
      Maternal physical and social factors, not energetics, contributed to differences
      among infants in growth trajectories, and infant growth temporally influenced
      successive reproductive events.

PMID- 18711739
TI  - Lifestyle incongruity, stress and immune function in indigenous Siberians: the
      health impacts of rapid social and economic change.
AB  - The purpose of this study was to investigate the impact of economic and cultural
      change on immune function and psychosocial stress in an indigenous Siberian
      population. We examined Epstein-Barr virus antibodies (EBV), an indirect
      biomarker of cell-mediated immune function, in venous whole blood samples
      collected from 143 Yakut (Sakha) herders (45 men and 98 women) in six communities
      using a cross-sectional study design. We modeled economic change through the
      analysis of lifestyle incongruity (LI), calculated as the disparity between
      socioeconomic status and material lifestyle, computed with two orthogonal scales:
      market and subsistence lifestyle. EBV antibody level was significantly negatively
      associated with both a market and a subsistence lifestyle, indicating higher cell
      mediated immune function associated with higher material lifestyle scores. In
      contrast, LI was significantly positively associated with EBV antibodies
      indicating lower immune function, and suggesting higher psychosocial stress,
      among individuals with economic status in excess of material lifestyle.
      Individuals with lower incongruity scores (i.e., economic status at parity with
      material resources, or with material resources in excess of economic status) had
      significantly lower EBV antibodies. The findings suggest significant health
      impacts of changes in material well-being and shifting status and prestige
      markers on health during the transition to a market economy in Siberia. The
      findings also suggest that relative, as opposed to absolute, level of economic
      status or material wealth is more strongly related to stress in the Siberian
      context.

PMID- 18711740
TI  - A new method for estimating age-at-death from the first rib.
AB  - A new method for estimating adult age-at-death from the first rib was developed
      as a modification of the Kunos et al. (Am J Phys Anthropol 110 (1999) 303-323)
      method. Data were collected on three aspects of the first rib (costal face, rib
      head, and tubercle facet) for 470 known-age males of Balkan ancestry collected as
      evidence during investigations conducted by the International Criminal Tribunal
      for the former Yugoslavia (ICTY). Ages-at-death range from 12 to 90 years (mean
      of 47.7 years). Several variables were extracted from the original study
      utilizing all three skeletal aspects of the first rib. This list was modified to
      11 variables as preliminary tests on seriations of the samples were undertaken. A
      cumulative probit model with age measured on a log scale was used to calculate
      the mean and standard deviation of the ages-of-transition for each component.
      Multivariate analysis of the three components was also performed. The lowest
      correlation (r = 0.079, controlling for age) was between the geometric shape of
      the costal face and the surface texture of the tubercle facet. Assuming a
      correlation of zero, these two traits were used to calculate the highest
      posterior density regions for estimating individual ages-at-death. Age-at-death
      estimates generated from 50 and 95% posterior density regions indicate that this
      method captures age-related change reaching the ninth decade. The Bayesian
      statistical approach used here produced a valuable and promising new method for
      estimating age-at-death. Additional research is necessary to determine if these
      highest posterior density regions produce results highly correlated with age in
      other samples and its applicability to females.

PMID- 18711741
TI  - Behavioral adaptations to heat stress and water scarcity in white-faced capuchins
      (Cebus capucinus) in Santa Rosa National Park, Costa Rica.
AB  - We examined thermoregulatory behaviors in a wild population of white-faced
      capuchins (Cebus capucinus) inhabiting a highly seasonal dry forest in Santa Rosa
      National Park (SRNP), Costa Rica. The dry season in SRNP lasts approximately 5
      months and is characterized by high ambient temperatures regularly exceeding 37
      degrees C, low relative humidity, and the near absence of precipitation. This
      study demonstrates that capuchins rest more and travel shorter distances during
      the hottest and driest hours of the day, and suggests that they extend their
      tongues to lower body temperature via evaporative cooling. Seasonal weather
      patterns and group movement data reported here are based on 940 h of observations
      on three social groups of capuchins (wet season: 370 h, dry season: 570 h). In
      the dry season, the proportion of time spent resting increased at higher
      temperatures whereas the proportion of time spent traveling decreased. Distance
      traveled between location points taken at half-hour intervals decreased
      significantly as temperature increased, although the correlation was not strong.
      Capuchins exposed their tongues during hot, dry, windy conditions, and this
      behavior was much more frequent in the dry season. Temperature was significantly
      higher and humidity significantly lower for "tongue-out" events than expected for
      a random event in the dry season. Finally, as surface water became scarce, home
      range areas of heavy use became increasingly centered on the remaining permanent
      water sources. These results suggest that heat stress and water scarcity are
      significant influences on the behavior of capuchins in hot, dry conditions.

PMID- 18711742
TI  - Surnames in Siberia: a study of the population of Yakutia through isonymy.
AB  - We studied the isonymic structure of the Republic of Sakha (Yakutia), in the
      Russian Federation, using the surname distributions of 491,259 citizens above 18
      years registered as residents in 2002. These were distributed in 35 districts and
      497 towns and settlements of the Republic. The number of different surnames was
      44,625. Matrices of isonymic distances between the 35 districts were tested for
      correlation with the geographic distance between the population centers of
      gravity of the districts. We found that, for the whole of Yakutia, Nei's distance
      was correlated with geographic distance (r = 0.693 +/- 0.027). A dendrogram of
      the 35 districts was built from the distance matrix, using the UPGMA method. The
      clusters identified by the dendrogram correlate with the geographic position of
      the districts. The correlation of random inbreeding calculated from isonymy,
      F(ST), with latitude was positive and highly significant but weak (r = 0.23). So,
      inbreeding was highest in the Arctic districts, and lowest in the South. Average
      alpha for 497 towns was 107, for 35 districts it was 311, and for the Republic
      433. The value of alpha was higher for Russian than for the local languages. The
      geographical distribution of alpha, high in the Center and South-East and lower
      in the North-West, is compatible with the settlement of groups of migrants moving
      from the South-East toward the center and the North of Yakutia. It is proposed
      that low-density demic diffusion of human populations results in high inbreeding
      and may have been a general phenomenon in the early phases of human radiations.

PMID- 18711743
TI  - Differential subcellular distribution and colocalization of the microsomal and
      soluble epoxide hydrolases in cultured neonatal rat brain cortical astrocytes.
AB  - The microsomal epoxide hydrolase (mEH) and soluble epoxide hydrolase (sEH)
      enzymes exist in a variety of cells and tissues, including liver, kidney, and
      testis. However, very little is known about brain epoxide hydrolases. Here we
      report the expression, localization, and subcellular distribution of mEH and sEH
      in cultured neonatal rat cortical astrocytes by immunocytochemistry, subcellular
      fractionation, Western blotting, and radiometric enzyme assays. Our results
      showed a diffuse immunofluorescence pattern for mEH, which colocalized with the
      astroglial cytoskeletal marker glial fibrillary acidic protein (GFAP). The GFAP
      positive cells also expressed sEH, which was localized mainly in the cytoplasm,
      especially in and around the nucleus. Western blot analyses revealed a distinct
      protein band with a molecular mass of approximately 50 kDa, the signal intensity
      of which increased about 1.5-fold in the microsomal fraction over the whole-cell
      lysate and other subcellular fractions. The polyclonal anti-human sEH rabbit
      serum recognized a protein band with a molecular mass similar to that of the
      affinity-purified sEH protein (approximately 62 kDa), the signal intensity of
      which increased over 1.7-fold in the 105,000g supernatant fraction over the cell
      lysate. Furthermore, the corresponding enzyme activities measured by using mEH-
      and sEH-selective substrates generally corroborated the immunocytochemical and
      Western blotting data. These results suggest that rat brain cortical astrocytes
      differentially coexpress mEH and sEH enzymes. The differential subcellular
      localization of mEH and sEH may play a role in the cerebrovascular functions that
      are known to be affected by brain-derived vasoactive epoxides.

PMID- 18711744
TI  - Chronic fluoxetine treatment improves ischemia-induced spatial cognitive deficits
      through increasing hippocampal neurogenesis after stroke.
AB  - Cognitive deficits, including spatial memory impairment, are very common after
      ischemic stroke. Neurogenesis in the dentate gyrus (DG) contributes to forming
      spatial memory in the ischemic brain. Fluoxetine, a selective serotonin reuptake
      inhibitor, can enhance neurogenesis in the hippocampus in physiological
      situations and some neurological diseases. However, whether it has effects on
      ischemia-induced spatial cognitive impairment and hippocampal neurogenesis has
      not been determined. Here we report that fluoxetine treatment (10 mg kg(-1),
      i.p.) for 4 weeks promoted the survival of newborn cells in the ischemic
      hippocampus and, consequently, attenuated spatial memory impairment of mice after
      focal cerebral ischemia. Disrupting hippocampal neurogenesis blocked the
      beneficial effect of fluoxetine on ischemia-induced spatial cognitive impairment.
      These results suggest that chronic fluoxetine treatment benefits spatial
      cognitive function recovery following ischemic insult, and the improved cognitive
      function is associated with enhanced newborn cell survival in the hippocampus.
      Our results raise the possibility that fluoxetine can be used as a drug to treat
      poststroke spatial cognitive deficits.

PMID- 18711746
TI  - Regulation of protein kinases and coregulatory interplay of S-100beta and
      serotonin transporter on serotonin levels in diabetic rat brain.
AB  - Protein kinases are critical component in the regulation of signal transduction
      pathways, including neurotransmitters. Our previous studies have shown that
      serotonin (5-HT) altered under diabetic condition was accompanied by alterations
      of protein kinase C-alpha (PKC-alpha) and CaMKII, and those alterations were
      reversed after insulin administration. The current study showed that alloxan
      induced diabetic animals revealed hyperglycemia and was associated with an
      increase in the content of 5-HT, PKC-alpha expression and PKC activity (P < 0.05)
      simultaneously in striatum (ST), midbrain (MB), pons medulla (PM), cerebellum
      (CB), and cerebral cortex (CCX) from 7 days to 60 days. Although the 5-HT levels
      in hippocampus (HC) and hypothalamus (HT) were not altered, the PKC-alpha
      expression and PKC activity showed increases (P < 0.05) in level in HC. Insulin
      administration reversed all these changes to a normal level. In contrast, the in
      vitro study has shown that the 5-HT levels correlated with PKC-alpha expressions
      as well as PKC activity (P < 0.05) only in ST, MB, and CB either after induction
      with phorbol 12-myristate 13-acetate (PMA) or blocking with chelerythrine,
      whereas PM and CCX remained elevated (P < 0.05), implying a regulatory role for
      PKC-alpha only in ST, MB, and CB. However, our consecutive studies have shown
      that the 5-HT level in PM was regulated by p38-mitogen-activated protein kinase
      (p38-MAPK) both in vivo and in vitro, whereas the 5-HT level in CCX was
      coregulated by S-100beta by protein-protein interaction with serotonin
      transporter (SERT) via 8-bromoadenosine 3',5'-cyclic monophosphate sodium salt (8
      Br-cAMP)-induced cAMP/PKAII pathway(s).

PMID- 18711745
TI  - Mitochondrial localization of DJ-1 leads to enhanced neuroprotection.
AB  - Mutations in DJ-1 (PARK7) cause recessively inherited Parkinson's disease. DJ-1
      is a multifunctional protein with antioxidant and transcription modulatory
      activity. Its localization in cytoplasm, mitochondria, and nucleus is recognized,
      but the relevance of this subcellular compartmentalization to its cytoprotective
      activity is not fully understood. Here we report that under basal conditions DJ-1
      is present mostly in the cytoplasm and to a lesser extent in mitochondria and
      nucleus of dopaminergic neuroblastoma SK-N-BE(2)C cells. Upon oxidant challenge,
      more DJ-1 translocates to mitochondria within 3 hr and subsequently to the
      nucleus by 12 hr. The predominant DJ-1 species in both mitochondria and nucleus
      is a dimer believed to be the functional form. Mutating cysteine 106, 53, or 46
      had no impact on the translocation of DJ-1 to mitochondria. To study the relative
      neuroprotective activity of DJ-1 in mitochondria and nucleus, DJ-1 cDNA
      constructs fused to the appropriate localization signal were transfected into
      cells. Compared with 30% protection against oxidant-induced cell death in wild
      type DJ-1-transfected cells, mitochondrial targeting of DJ-1 provided a
      significantly stronger (55%) cytoprotection based on lactate dehydrogenase
      release. Nuclear targeting of DJ-1 preserved cells equally as well as the wild
      type protein. These observations suggest that the time frame for the
      translocation of DJ-1 from the cytoplasm to mitochondria and to the nucleus
      following oxidative stress is quite different and that dimerized DJ-1 in
      mitochondria is functional as an antioxidant not related to cysteine
      modification. These findings further highlight the multifaceted functions of DJ-1
      as a cytoprotector in different cellular compartments.

PMID- 18711747
TI  - Neuroprotective effects of erythropoietin posttreatment against kainate-induced
      excitotoxicity in mixed spinal cultures.
AB  - Although the neuroprotective effects of erythropoietin (EPO) preconditioning are
      well known, the potential of postapplied EPO to protect neurons against
      excitotoxic injury has not been clearly established. Here we show that kainate
      (KA)-induced excitotoxicity, which plays a key role in secondary spinal cord
      injury, decreased neuron survival, inhibited neurite extension, and significantly
      reduced the expression of erythropoietin receptors (EpoR) in cultured spinal
      neurons. Posttreatment with EPO for 48 hr protected neurons against KA-induced
      injury, opposing KA-induced apoptosis and promoting regrowth of motoneuron
      neurites. These neuroprotective effects were paralleled by a restoration of EpoR
      expression. The importance of the EpoR signaling pathway was demonstrated using
      an EpoR blocking antibody, which neutralized the neuroprotective action of EPO
      posttreatment and prevented EPO-induced increases in EpoR expression. We also
      found that up-regulated EpoR stimulated the Janus kinase 2 (JAK2) pathway, which
      is known to facilitate neuronal growth and neurite regeneration. Although EPO
      posttreatment modestly attenuated KA-induced reactive gliosis in mixed neuron
      glial cultures, blocking EpoR activity did not alter glial fibrillary acidic
      protein expression or astrocyte proliferation. In conclusion, 48 hr treatment
      with EPO following KA exposure induced EpoR-dependent protection against
      excitotoxic injury, demonstrating that preconditioning is not a prerequisite for
      neuroprotection by EPO. The neuroprotective effects of EPO posttreatment were
      mediated by an EpoR-dependent signaling pathway that possibly involves JAK2. The
      neuroprotective effect of EPO posttreatment against KA excitotoxicity appears to
      reflect direct effects on neurons and not indirect effects mediated by
      astrocytes.

PMID- 18711748
TI  - Genetic disruption of cyclooxygenase-2 does not improve histological or
      behavioral outcome after traumatic brain injury in mice.
AB  - Increasing evidence suggests a role for cyclooxygenase-2 (COX-2) in traumatic
      brain injury (TBI). In the present study, the role of COX-2 in TBI was
      investigated using COX-2 gene-disrupted (COX-2 null) mice and wild-type (WT)
      controls that were subjected to the controlled cortical impact (CCI) model of
      TBI. There was increased expression of COX-2 in ipsilateral hippocampus in WT
      mice subjected to CCI. CCI resulted in a significant increase in prostaglandin
      E(2) concentrations in WT compared with COX-2 null hippocampi. There was a
      significant increase in TUNEL staining of CA1 neurons 24 hr after CCI in WT, but
      not in COX-2 null mice, compared with sham-operated controls, which is consistent
      with a protective role for COX-2 in the early phase of injury after TBI. However,
      there was no difference in lesion volume 21 days after CCI in COX-2 null and WT
      mice. COX-2 gene disruption did not alter Morris water maze performance. Taken
      together, these results suggest only a minor role for COX-2 activity in
      determining outcome after TBI in mouse.

PMID- 18711750
TI  - 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one inhibits neurite outgrowth and causes
      neurite retraction in PC12 cells independently of soluble guanylyl cyclase.
AB  - The effect of the potent soluble guanylyl cyclase (sGC) inhibitor 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) on neurite outgrowth and
      retraction was investigated in PC12 cells and SH-SY5Y human neuroblastoma cells.
      ODQ inhibited neurite outgrowth and triggered neurite retraction in the cells
      stimulated with nerve growth factor (NGF), staurosporine, or Y-27632. The nitric
      oxide (NO) scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3
      oxide (PTIO) had little effect on neurite outgrowth induced by Y-27632 or
      staurosporine. In the presence of ODQ, treatment of the cells with the cell
      permeable cGMP analogue 8-bromo-cGMP failed to retrigger Y-27632- and
      staurosporine-induced neurite outgrowth. Furthermore, the depletion of sGC by RNA
      interference failed to prevent Y-27632- and staurosporine-induced neurite
      outgrowth. These results indicate that the NO/sGC/cGMP signaling cascade is not
      critically involved in ODQ-induced neurite remodeling. The MEK inhibitor PD98059
      did not inhibit neurite outgrowth, and Y-27632 and staurosporine did not induce
      ERK phosphorylation, suggesting that the inhibitory effect of ODQ on neurite
      outgrowth is independent of the ERK signaling pathway. In contrast, pretreatment
      with dithionite or a hemin-glutathione mixture reversed the inhibitory effect of
      ODQ on Y-27632- and staurosporine-induced neurite outgrowth, indicating that ODQ
      might act on an intracellular redox-sensitive molecule. We conclude that ODQ
      inhibits Y-27632- and staurosporine-induced neurite outgrowth and triggers
      neurite retraction in an sGC-independent manner in neuronal cells and suggest
      that oxidation of unidentified redox-sensitive protein could be responsible for
      these effects.

PMID- 18711749
TI  - Nitric oxide donor up-regulation of SDF1/CXCR4 and Ang1/Tie2 promotes neuroblast
      cell migration after stroke.
AB  - We tested the hypothesis that a nitric oxide donor, DETA-NONOate, up-regulates
      stromal cell-derived factor-1 (SDF1) and angiopoietin 1 (Ang1) in the ischemic
      brain and their respective receptors chemokine CXC motif receptor 4 (CXCR4) and
      Tie2 in the subventricular zone (SVZ) and thereby promote SVZ neuroblast cell
      migration after stroke. C57BL/6J mice were subjected to middle cerebral artery
      occlusion (MCAo), and 24 hr later DETA-NONOate (0.4 mg/kg) or phosphate-buffered
      solution was intravenously administered. Mice were sacrificed at 14 days for
      histological assessment or sacrificed at 3 days for analysis by real-time
      polymerase chain reaction and migration after MCAo. To elucidate whether
      SDF1/CXCR4 and Ang1/Tie2 pathways mediate DETA-NONOate-induced SVZ migration
      after stroke, SDF1alpha, Ang1 peptide, a specific antagonist of CXCR4 (AMD3100),
      and a neutralizing antibody of Tie2 (anti-Tie2) were used in vitro. DETA-NONOate
      significantly increased the percentage area of doublecortin (DCX, a marker of
      migrating neuroblasts)-immunoreactive cells in the SVZ and ischemic boundary
      zone. DETA-NONOate significantly increased the expression of SDF1 and Ang1 in the
      ischemic border and up-regulated CXCR4 and Tie2 in the SVZ compared with MCAo
      control. DCX-positive cell migration from SVZ explants was significantly
      increased in the DETA-NONOate treatment group compared with MCAo-alone animals.
      In vitro, SDF1alpha and Ang1 significantly increased SVZ explants cell migration.
      In addition, inhibition of CXCR4 or Tie2 significantly attenuated DETA-NONOate
      induced SVZ cell migration. Our data indicate that treatment of stroke with a
      nitric oxide donor up-regulates SDF1/CXCR4 and Ang1/Tie2 pathways and thereby
      likely increases SVZ neuroblast cell migration.

PMID- 18711751
TI  - Validation of reference genes for normalization of real-time quantitative RT-PCR
      data in traumatic brain injury.
AB  - Careful validation of reference genes used for the normalization of real-time RT
      PCR data is required to obtain accurate results regarding gene expression. We
      evaluated the stability of seven commonly used reference genes in the cerebral
      cortex and hippocampus of rats 3 days following traumatic brain injury (TBI).
      HPRT, SDHA, and GUSB were found to be the most stable reference genes in the
      cerebral cortex, whereas B2MG, TBP, and GAPDH were the most stable in the
      hippocampus. The use of three reference genes was determined to be the optimal
      number for accurate normalization of data. To illustrate this point, when our
      gene of interest, substance P (SP), was normalized against the three most stable
      reference genes in both brain areas, we found no significant difference between
      injured and uninjured rats at the 3-day time point. However, when our SP data
      were normalized to each reference gene individually, SP mRNA level was highly
      variable depending on the reference gene chosen. The results of the present study
      highlight the importance of validating reference genes to be used for real-time
      RT-PCR analysis. The use of the most stable reference genes presented here will
      allow more accurate normalization of gene expression data in TBI.

PMID- 18711752
TI  - Positive and negative ZnO micropatterning on functionalized polymer surfaces.
AB  - Patterned ZnO deposition on substrates has received increasing attention because
      of its great potential in photocatalysis, energy conversion, and electro-optical
      techniques. Chemical solution growth is especially promising for organic
      substrates due to its very mild reaction conditions. Here this method is used on
      functionality-patterned polymer surfaces in order to fabricate positive and
      negative ZnO micropatterns. A ZnO film made of arrayed rods, typically 500-750 nm
      in diameter and 2.5 microm in length, is selectively obtained on sulfated and
      hydroxylated regions of biaxially oriented poly(propylene), giving rise to
      positive patterns. For reactive polyesters such as poly(ethylene terephthalate),
      the ZnO rods selectively remain on the unmodified original regions, creating
      negative patterns. Unlike complex photolithography procedures, the irradiation
      and patterning processes do not require the use of positive or negative
      photoresists, and possible damage from acidic solutions on the underlying
      substrate during the chemical etching process is avoided. The process thus proves
      to be a simple, creditable, and low-cost method, which could be easily applied on
      a variety of inert and reactive polymer surfaces.

PMID- 18711753
TI  - Functionalized-quantum-dot-liposome hybrids as multimodal nanoparticles for
      cancer.
AB  - Functionalized-quantum-dot-liposome (f-QD-L) hybrid nanoparticles are engineered
      by encapsulating poly(ethylene glycol)-coated QD in the internal aqueous phase of
      different lipid bilayer vesicles. f-QD-L maintain the QD fluorescence
      characteristics as confirmed by fluorescence spectroscopy, agarose gel
      electrophoresis, and confocal laser scanning microscopy. Cationic f-QD-L hybrids
      lead to dramatic improvements in cellular binding and internalization in tumor
      cell monolayer cultures. Deeper penetration into three-dimensional multicellular
      spheroids is obtained for f-QD-L by modifying the lipid bilayer characteristics
      of the hybrid system. f-QD-L are injected intratumorally into solid tumor models
      leading to extensive fluorescent staining of tumor cells compared to injections
      of the f-QD alone. f-QD-L hybrid nanoparticles constitute a versatile tool for
      very efficient labeling of cells ex vivo and in vivo, particularly when long-term
      imaging and tracking of cells is sought. Moreover, f-QD-L offer many
      opportunities for the development of combinatory therapeutic and imaging
      (theranostic) modalities by incorporating both drug molecules and QD within the
      different compartments of a single vesicle.

PMID- 18711754
TI  - Biomimetic synthesis of gold nanocrystals using a reducing amphiphile.
AB  - The first synthesis of a chelating and reactive surfactant derived from citric
      acid and a short silicone as hydrophobic tail is described. Aqueous solutions of
      this reactive amphiphile spontaneously induce gold ion reduction, particle
      nucleation, and further direct crystal growth. The process, both pH and light
      dependent, occurs through lipid-directed assembly of metal ions, their reduction
      and subsequent lipid-directed growth to yield ultrathin (approximately 7 nm
      thick) quasi two-dimensional gold nanocrystals.

PMID- 18711755
TI  - Facile one-pot synthesis of self-assembled silver@polypyrrole core/shell
      nanosnakes.

PMID- 18711756
TI  - Contractility-dependent modulation of cell proliferation and adhesion by
      microscale topographical cues.
AB  - Engineering of cellular assembly on biomaterial scaffolds by utilizing microscale
      topographical cues has emerged as a powerful strategy in cardiovascular tissue
      engineering and regenerative medicine. However, the mechanisms through which
      these cues are processed to yield changes in canonical cell behaviors remain
      unclear. Previously, we showed that when mixtures of cardiomyocytes and
      fibroblasts were cultured on polydimethylsiloxane surfaces studded with
      microscale pillars (micropegs), fibroblast proliferation was dramatically
      suppressed, which suggests that the micropegs could be exploited to minimize
      fibrosis and scar formation. Here, we demonstrate that this effect relies on
      altered adhesive and micromechanical interactions between individual cells and
      micropegs. First, we show that the proliferation of a cell physically attached to
      a micropeg is significantly lower than that of a cell cultured on a featureless
      region of the substrate. Micropeg adhesion is accompanied by a marked elongation
      in cell and nuclear shape. When fibroblast contractility is pharmacologically
      attenuated through low-dose inhibition of either Rho-associated kinase or myosin
      light chain kinase, the potency with which micropeg adhesion suppresses cell
      proliferation is significantly reduced. Together, our results support a model in
      which cell fate decisions may be directly manipulated within tissue engineering
      scaffolds by the inclusion of microtopographical structures that alter cellular
      mechanics.

PMID- 18711759
TI  - Enteral nutrition in adult Crohn's disease: present status and perspectives.
AB  - Enteral nutrition has long been a therapeutic alternative often used in adult
      Crohn's disease patients to obtain remission or clinical response, especially in
      those not responding to conventional therapy such as corticosteroids. However,
      the increasing use of immunosuppressors (6-mercaptopurine and azathioprine,
      methotrexate, etc.), and the advent of biotherapies (especially anti-tumor
      necrosis factor-alpha (TNF-alpha) antibodies), decreased its use in adult Crohn's
      disease. Nevertheless, enteral nutrition remains of interest in patients
      presenting concomitant malnutrition (in particular in nonobstructed patients
      needing surgery), or in those intolerant or who failed to other therapeutics. In
      addition, recent studies provide data indicating its potential interest in
      maintenance therapy in selected patients groups. Finally, future research (in
      particular in the field of immuno- or pharmaconutrition) could lead to enteral
      formula's improvement, with better tolerance and acceptability, as well as
      increased efficacy.

PMID- 18711760
TI  - Rapid screening method for intact glucosinolates in Chinese medicinal herbs by
      using liquid chromatography coupled with electrospray ionization ion trap mass
      spectrometry in negative ion mode.
AB  - An optimized method using liquid chromatography coupled with electrospray
      ionization ion trap mass spectrometry (LC/ESI-ITMS) in negative ion mode has been
      developed for screening different structural classes of intact glucosinolates in
      six Chinese medicinal herbs. The glucosinolates were extracted with hot
      methanol/water (70:30 v/v) and separation of the individual glucosinolates was
      achieved using a reversed-phase C18 column with an aqueous ammonium
      acetate/methanol gradient. Identification of the intact glucosinolates was based
      on the detection of compounds with a constant neutral loss of 242 Da
      corresponding to the combined loss of anhydroglucose (162 Da) and sulfur trioxide
      (80 Da) in collision-induced dissociation. The structures of the identified
      glucosinolates were confirmed with the use of group-specific product ions at m/z
      195, 241, 259, 275 in their corresponding MS/MS product ion spectra.
      Differentiation of intact glucosinolates was achieved through their respective
      retention times and molecular masses as well as the characteristic product ions.
      The limits of detection were at the low nanogram level per injection, based on
      constant neutral loss scans. Significant variation in the compositions of intact
      glucosinolates was identified in the cruciferous herbs. This method was applied
      in the differentiation and quality control of two pairs of easily confused herbs.

PMID- 18711761
TI  - Acupuncture analgesia: a review of its mechanisms of actions.
AB  - The mechanism of acupuncture analgesia (AA) has been widely explored since the
      1970s. Early studies investigated the relationship between acupuncture and
      endogenous opiates (beta-endorphin, enkephalin, endomorphin and dynorphin).
      Before the 1990s, most experts agreed on the concept that in normal animal
      models, lower frequency electroacupuncture (EA) stimulates the release of beta
      endorphin, enkephalin and endomorphin, which in turn activates the mu- and delta
      opioid receptors, and that higher frequency EA stimulates dynorphin which
      activates the kappa-opioid receptor. Besides endogenous opiates, our studies have
      focused on serotonin. The serotoninergic descending inhibitory pathway is
      suggested to be an important mechanism of acupuncture analgesic, collaborating
      with endogenous opiates. Many efforts have been made to clarify these mechanisms,
      but to date no satisfactory consensus has been reached. In the late 1990s,
      researchers began to focus on the different analgesic effects of EA between
      normal and hyperalgesic animal models. Published data from these studies imply
      that normal and hyperalgesic animals respond differently to EA. Results from
      experiments on the anti-hyperalgesia effect of EA have raised a new issue about
      the influences of EA on receptors to excitatory amino acid in the spinal cord
      level. Results from various studies have shown that these receptors play a role
      in the mechanism of AA. Recently, research on the autonomic nervous system (ANS)
      seem to indicate its connection with acupuncture. The inflammatory reflex (via
      the ANS) might be a crucial part of anti-hyperalgesia elicited by acupuncture,
      and this reflex, which regulates the immune system in the organism, can elucidate
      not only the mechanism of AA but also the mechanism of acupuncture applied to
      other inflammatory conditions. Innovation of functional image study enables us to
      analyze the responses of cortex on living human body to acupuncture. However,
      results of these experiments are still controversial. After 30 years of
      acupuncture research, there are still many puzzles left to be solved regarding
      the mechanism of AA.

PMID- 18711762
TI  - Effects of 14-week Tai Ji Quan exercise on metabolic control in women with type 2
      diabetes.
AB  - The present study investigated the effects of 14 weeks of practicing Tai Ji Quan
      (TJQ) on metabolic control and lipid metabolism in women with type 2 diabetes.
      Twenty Beijing female residents (57.4 +/- 6.2 years) were recruited and were
      randomly assigned to either the TJQ training or the control group. In the TJQ
      group, the exercise duration was 1 hour per day and 5 days a week for 14 weeks.
      FPG, GSP, FPI, TC, HDL-C, LDL-C, TG, resting blood pressures and heart rate were
      measured before and after the 14 weeks in the 2 groups. It was found that after
      14 weeks, the TJQ group had significantly lower FPG, GSP, TG and higher FPI
      concentration, whereas there were no significant differences in TC, HDL-C and LDL
      C. It was concluded that TJQ exercise could be used as an intervention tool to
      improve glycaemic control and serum TG level in the elderly people. Future
      research with TJQ of different styles and exercise of different intensities were
      recommended.

PMID- 18711763
TI  - The distribution of Yin-Deficient symptoms and their relationship on survival
      rate in cancer patients with Yin-Deficiency.
AB  - Yin-Deficiency (YD), representing a status of the human body under lack of
      nutrition and fluid in traditional Chinese medicine, is commonly seen in late
      stage of cancer patients. It is not known whether the severity of YD related
      symptoms/signs can predict the survival rate of cancer patients. This study
      evaluated the distribution of Yin-deficiency symptoms/signs (YDS) in cancer
      patients with YD, and investigated whether the severity of YDS can predict the
      survival rate of cancer patients with YD. From 5 January 2007 to 5 May 2007, we
      selected 43 cancer patients with diagnosis of YD from hospitalized patients and
      outpatients. The severity of YD was evaluated by a questionnaire. We further
      estimated the cumulative probabilities of the survival rates over 4 months since
      the start of study by the Kaplan-Meier product-limit method, and compared the
      differences among groups with various severities in each symptom/sign with the
      use of the log-rank test. The results revealed that, the 3 most common YDS were
      sleeplessness with annoyance, less or non-coated tongue with or without redness
      and dry mouth. In the survival rate analysis, only 2 parameters, rapidly small
      pulse (p = 0.002) and less-or non-coated tongue with paleness (p = 0.017), were
      found to be related to the decrease of cancer patients with YD. This suggests
      that, both rapidly small pulse and less-or non-coated tongue without redness may
      be used as predictors for the estimation of survival rate in cancer patients with
      YD.

PMID- 18711764
TI  - Randomized phase II trial on mitomycin-C/cisplatin +/- KLT in heavily pretreated
      advanced breast cancer.
AB  - A randomized phase II study using mitomycin (MMC)/cisplatin (DDP) regimen with or
      without Kanglaite (KLT, a traditional Chinese medicine) as salvage treatment was
      conducted to exploit KLT's potential effects on patients with advanced breast
      cancer (ABC). Triweekly regimen consisted of mitomycin (8 mg/m(2)) administered
      intravenously on day 1, and cisplatin (25 mg/m(2)) intravenously on days 1 to 3.
      KLT (100 ml) was given intravenously per day on days 1 to 14 every 3 weeks.
      Between April 2006 and July 2007, 60 patients with a median age of 48 years were
      randomized into MMC/DDP with or without KLT treatment. In all, the objective
      response rate (ORR) was 17.5%. There were no significant differences between
      experimental and control treatments in terms of ORR (14.3% vs. 20.7%, p = 0.730),
      clinical benefit rates (24.1% vs. 28.6%, p = 0.468), median time to progression
      (TTP; 3.63 vs. 4.0, p = 0.872), and overall survival (OS; 7.17 vs. not reached, p
      = 0.120). The median TTP for patients with complete or partial responses was 6.0
      months, but only 2.1 months for patients with stable or progressive disease (SD
      or PD; p = 0.028). While the median OS for patients who obtained clinical benefit
      from chemotherapy was not reached, that of patients with SD of no more than 6
      months or PD was only 7.17 months (p = 0.004). There is no additional benefit
      when KLT is added to the MMC/DDP doublet in the management of ABC. Patients who
      obtained clinical benefit from chemotherapy had a longer TTP and OS.

PMID- 18711765
TI  - Symptom combinations assessed in traditional Chinese medicine and its predictive
      role in ACR20 efficacy response in rheumatoid arthritis.
AB  - The predictive roles of symptom combination traditionally evaluated in
      traditional Chinese medicine (TCM) in the treatment of rheumatoid arthritis (RA)
      were explored. Three hundred and ninety six patients were randomly divided into
      197 subjects receiving Western medicine therapy (WM) and 199 subjects receiving
      TCM therapy (TCM). A complete physical examination and 18 clinical manifestations
      typically assessed in TCM were recorded before the randomization. The ACR
      responses were used for efficacy evaluation. ACR20 and 50 responses with WM
      treatment were higher than in the TCM group. The 18 symptoms in RA could be
      clustered into 4 symptom combinations with factor analysis, which represent joint
      symptoms, cold pattern, deficiency pattern and hot pattern in TCM respectively.
      TCM would be more effective in patients with weak-symptom combination 3
      (deficiency pattern in TCM), and WM would be more effective in patients with
      symptom combination 2 (cold pattern in TCM). Symptom combinations judged with TCM
      may have influence on the efficacy of therapy in the treatment of RA.

PMID- 18711766
TI  - Panax Notoginseng Burk attenuates impairment of learning and memory functions and
      increases ED1, BDNF and beta-secretase immunoreactive cells in chronic stage
      ischemia-reperfusion injured rats.
AB  - Panax Notoginseng Burk (PN) has been reported to improve blood circulation, as
      well as learning and memory functions. The purpose of the present study was to
      investigate the effect of PN on learning and memory functions in chronic cerebral
      infarct rats. A cerebral infarct animal model was established by blocking the
      blood flow of both common carotid arteries and right middle cerebral artery for
      90 min followed by reperfusion for 4 weeks. PN (0.5 g/kg) was administered orally
      3 days per week for 4 weeks, whereas the control group provided bait and water
      only. The learning and memory functions were estimated by measuring how
      successful rats were able to negotiate an 8-arm radial maze test; the test was
      performed after operation once a week for 4 weeks. Finally, the rats were
      sacrificed and their brains were removed. The brains were sectioned and analyzed
      for ED1, glial fibrillary acid protein (GFAP), nuclear factor-kappaB, and brain
      derivative neurotrophin factor (BDNF) and beta-secretase by immunostaining.
      Cerebral infarct rats given PN were able to successfully navigate the 8-arm
      radial maze test four weeks after cerebral infarction. PN also increased ED1,
      BDNF and beta-secretase immunoreactive cells, but did not increase GFAP and NF
      kappaB immunoreactive cells. PN attenuated the reduction in learning and memory
      functions induced by cerebral infarction in cerebral ischemia-reperfusion injured
      rats; it also increased the amount of activated microglia and BDNF. These data
      suggest that the effect of PN, at least in part, is closely related to the
      increase in BDNF that was generated by activated microglia. The effect that PN
      has on astrocytes, NF-kappaB and beta-secreatase immunoreactive cells requires
      further study.

PMID- 18711767
TI  - Effect of total flavonoids of Chrysanthemum indicum on the apoptosis of
      synoviocytes in joint of adjuvant arthritis rats.
AB  - Chrysanthemum is a traditional Chinese medicine used in China to treat
      inflammatory diseases. The total flavonoids Chrysanthemum indicum (TFC) were
      extracted from the dried bud of Chrysanthemum indicum. Our previous study had
      demonstrated that TFC was a new class of effective anti-inflammation, analgesia
      and immunoloregulation agents. In this study, we established an adjuvant
      arthritis (AA) model by injection of Freund's Complete Adjuvant (FCA) to
      investigate the effect of TFC on the apoptosis of synoviocytes in AA Rats.
      Synoviocytes isolated from knee joint of rats were treated with different doses
      of TFC in vitro. Synoviocytes proliferation was measured by MTT assay, and DNA
      fragmentations were evaluated on agarose gel electrophoresis. The levels of
      caspase-3 cleaved fragments were analyzed by Western blot. The annexin V stain
      assay was used to explore the inhibition of caspase-3 on the amelioration of
      synoviocytes apoptosis. The results showed that TFC inhibited the proliferation
      of synoviocytes. Electrophoresis showed higher ladders of DNA bands in the TFC
      group. Cleaved fragments of caspase-3 were increased significantly. Furthermore,
      the apoptotic synoviocytes were markedly decreased by the caspase-3 specific
      inhibitor. These results suggest that TFC could induce synoviocytes apoptosis and
      suppress proliferation of synoviocytes in adjuvant-induced arthritis rats.

PMID- 18711768
TI  - The protective effect of Yi-Qi-Yang-Yin-Ye, a compound of traditional Chinese
      herbal medicine in diet-induced obese rats.
AB  - The present study was undertaken to determine the effect of Yi-Qi-Yang-Yin-Ye (Y
      Q-Y-Y-Y), a compound of Traditional Chinese Herbal Medicine, on insulin
      resistance (IR) in the diet-induced obese rat model induced by intravenous
      injection with a low dose of streptozotocin and fed a high fat and high caloric
      diet. Y-Q-Y-Y-Y (2, 4, 8 g/kg) was administered via gavage daily for 4 weeks. The
      results showed that Y-Q-Y-Y-Y treatment decreased the levels of body weight,
      total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol
      (LDL-C), free fatty acid (FFA), insulin (INS) and fast blood glucose (FBG) and
      increased the level of high density lipoprotein-cholesterol (HDL-C) in the diet
      induced obese rats. Glucose tolerance was improved in the diet-induced obese rats
      treated with Y-Q-Y-Y-Y as well as GIR (glucose infusion rate) in the
      hyperinsulinemic euglycemic clamp experiment compared to the model control rats
      (p < 0.01). Moreover, treatment with Y-Q-Y-Y-Y up-regulated glycogen contents in
      both liver and skeletal muscle and increased insulin receptor amounts on the
      erythrocytes surface as assessed by using (125)I-labeled auto-antibodies against
      insulin receptors. Taken together, our data suggested that Yi-Qi-Yang-Yin-Ye
      ameliorates insulin resistance in the diet-induced obese rats.

PMID- 18711769
TI  - The antithrombotic effect of borneol related to its anticoagulant property.
AB  - Borneol is consumed excessively in China and Southeast Asian countries
      particularly in combined formula for preventing cardiovascular disease, but few
      studies were conducted on its effects on thrombosis. In this study, the
      antithrombotic and antiplatelet activities of borneol were investigated on
      thrombosis in vivo and on platelet aggregation ex-vivo. In addition, the
      coagulation parameters and influence on fibrinolytic activity were also assessed.
      The results showed that borneol had concentration dependent inhibitory effects on
      arterio-venous shunt and venous thrombosis but no effect on ADP and AA-induced
      platelet aggregation. Meanwhile, borneol prolonged the coagulation parameters for
      prothrombin time (PT) and thrombin time (TT), but did not show any fibrinolytic
      activity. It suggested that the antithrombotic activity of borneol and its action
      in combined formula for preventing cardiovascular diseases might be due to
      anticoagulant activity rather than antiplatelet activity.

PMID- 18711770
TI  - Green tea extract enhances the selective cytotoxic activity of Zizyphus jujuba
      extracts in HepG2 cells.
AB  - Anticarcinogenic effects attributed to phytochemicals may be based on
      synergistic, additive, or antagonistic interactions of many compounds. In our
      previous study, we demonstrated that the chloroform fraction (CHCl(3)-F) from Z.
      jujuba has anticancer activity in HepG2 cells. In China, many people drink jujuba
      tea and believe in the synergic effects of jujuba and tea for better health. We
      therefore investigated the effects of CHCl(3)-F and green tea extract (GTE), and
      their underlying mechanisms of action in HepG2 cells. Our results showed that GTE
      enhanced the effect of CHCl(3)-F on cell viability in HepG2 cells, without
      cytotoxicity in rat hepatocytes, which was used as a normal cell model.
      Furthermore, combination of CHCl(3)-F and GTE caused an effect on G1 phase arrest
      but not on apoptosis. Interestingly, the mechanism of the G1 arrest was
      associated, not with an increase in p27(Kip1) levels and the hypohosphorylation
      of Rb, which are pathways used by CHCl(3)-F on G1 arrest in HepG2 cells, but with
      increases in p53 and p21(Waf1/Cip1) levels, and a decrease in cyclin E levels.
      Collectively, our findings suggest that combination of CHCl(3)-F and GTE produces
      an enhanced cell growth inhibition effect, and that the resultant G1 arrest was
      caused via a different mechanism as that of CHCl(3)-F treatment alone.

PMID- 18711771
TI  - Inhibitory effects of Baicalin on ultraviolet B-induced photo-damage in
      keratinocyte cell line.
AB  - Baicalin, one kind of Chinese herbal medicine with anti-inflammatory and anti
      oxidant property, has been commonly used as a clinical medicine. However, little
      has been known about the effects of Baicalin on ultraviolet (UV) induced photo
      aging and photo-carcinogenesis. The photoproduct is critical to the initial event
      of UV-induced photo-carcinogenesis. The purpose of the present study was to
      investigate whether Baicalin, in immortalized human keratinocyte HaCaT cells,
      could inhibit ultraviolet-B (UVB) induced skin damage and its possible underlying
      mechanisms, such as inhibiting UVB-induced cytotoxicity and apoptosis,
      cyclobutane pyrimidine dimers (CPDs), down-regulating the expression of
      regulatory proteins which are related to cell apoptosis and DNA damage/repair.
      Our study revealed that Baicalin treatment could inhibit the UVB-induced
      cytotoxicity, apoptosis and CPD level. It also decreased the mRNA expression of
      apoptosis-regulatory genes (p53-p21 and c-fos), the protein levels of p53,
      proliferating cell nuclear antigen (PCNA) and repair protein A (RPA), and the
      secretion of cytokines [interleukin(IL)-6 and tumor necrosis factor (TNF-alpha)].
      These results suggested that Baicalin may have an inhibitory effect on the UVB
      induced photo-damage by blocking the relevant cytokine secretion and expression
      of p53-p21, c-fos, PCNA and RPA genes.

PMID- 18711772
TI  - Active compounds isolated from traditional Chinese prescription Wen-Pi-Tang
      protecting against peroxynitrite-induced LLC-PK(1) cell damage.
AB  - Wen-Pi-Tang, a traditional Chinese prescription, has been widely used for the
      treatment of patients with moderate chronic renal failure in China. Although the
      protective effect of Wen-Pi-Tang on peroxynitrite (ONOO(-))-induced renal tubular
      epithelial LLC-PK(1) cell damage was elucidated in our previous research, the
      active components of Wen-Pi-Tang have not yet been fully clarified. Therefore in
      the present study, we investigated the active components by using a cellular
      ONOO(-)generation system. As a result, p-coumaric acid, 4-(4'-hydroxylphenyl)-2
      butanone 4'-O-glucopyranoside, gallic acid 3-O-(6'-O-galloyl)-beta-d
      glucopyranoside, procyanidin B-1, procyanidin B-3, and (+)-catechin were isolated
      as active compounds inhibiting cellular ONOO(-) formation and cytotoxicity. In
      particular, the content of (+)-catechin was significantly higher than those of
      the other compounds, and the (+)-catechin structure was located in procyanidins B
      1 and B-3. Therefore, the major bioactivity of Wen-Pi-Tang against ONOO(-)
      induced cytotoxicity in LLC-PK(1) cells was thought to be mediated by (+)
      catechin. Although we cannot disregard the synergetic effect of various
      components in Wen-Pi-Tang, (+)-catechin is a major active compound protecting
      against ONOO(-)-induced LLC-PK(1) cell damage and may be used as an index to
      qualify the ONOO(-)-inhibitory activity of Wen-Pi-Tang extract.

PMID- 18711773
TI  - Functional analysis of cultured neural cells for evaluating cold/cool- and
      hot/warm-natured Chinese herbs.
AB  - Recently, modern scientific research has been required to understand
      pharmacological basis of traditional Chinese medicine (TCM) theory based on the
      ancient clinical experience, and to investigate the molecular mechanisms of
      action of Chinese herbs. Here, 20 Chinese herbs, classified into 4 properties
      (hot, warm, cold and cool) of TCM, were analyzed for their ability to exhibit
      antioxidant action, to enhance glucose uptake by murine microglia N9 cells, and
      to influence neurotransmitter norepinephrine (NE) release from rat
      pheochromocytoma PC12 cells. We found a generally protective effect of both
      hot/warm-natured and cold/cool-natured herbs against H(2)O(2)-induced N9 cell
      death, partially by elevating superoxide dismutase (SOD) activity. Glucose uptake
      was elevated after treatment with some hot/warm-natured herbs. In addition, most
      herbs with hot/warm nature tended to stimulate NE release, while such stimulatory
      effect was not observed in the herbs with cold/cool nature. Two cold/cool-natured
      herbs, Rhizoma coptidis and Radix scutellariae, even significantly suppressed the
      release. These results suggest that the distinct abilities of Chinese herbs to
      regulate neural cell functions appear to be correlated with their natures
      identified in traditional TCM theory, and may be a useful guide for their utility
      in neural degenerative diseases.

PMID- 18711774
TI  - Relationship Between San-Huang-Xie-Xin-Tang and its herbal components on the gene
      expression profiles in HepG2 cells.
AB  - Traditional Chinese medicine (TCM) has been used for thousands of years. Most
      Chinese herbal formulae consist of several herbal components and have been used
      to treat various diseases. However, the mechanisms of most formulae and the
      relationship between formulae and their components remain to be elucidated. Here
      we analyzed the putative mechanism of San-Huang-Xie-Xin-Tang (SHXXT) and defined
      the relationship between SHXXT and its herbal components by microarray technique.
      HepG2 cells were treated with SHXXT or its components and the gene expression
      profiles were analyzed by DNA microarray. Gene set enrichment analysis indicated
      that SHXXT and its components displayed a unique anti-proliferation pattern via
      p53 signaling, p53 activated, and DNA damage signaling pathways in HepG2 cells.
      Network analysis showed that most genes were regulated by one molecule, p53. In
      addition, hierarchical clustering analysis showed that Rhizoma Coptis shared a
      similar gene expression profile with SHXXT. These findings may explain why
      Rhizoma Coptis is the principle herb that exerts the major effect in the herbal
      formula, SHXXT. Moreover, this is the first report to reveal the relationship
      between formulae and their herbal components in TCM by microarray and
      bioinformatics tools.

PMID- 18711775
TI  - Aldose reductase inhibitors from Viola hondoensis W. Becker et H Boss.
AB  - The isolation and characterization of rat lens aldose reductase inhibitors from
      the Viola hondoensis W. Becker et H Boss were conducted. The extracts and organic
      fractions from V. hondoensis were tested. The MeOH extract and EtOAc fraction
      were found to exhibit potent rat lens aldose reductase inhibition in vitro, their
      IC(50) being 1.2 and 0.6 microg/ml, respectively. One major isoflavonoid
      glycoside was isolated from the ethyl acetate soluble fraction of V. hondoensis.
      Kakkalide was found to be the potential rat lens aldose reductase inhibitor
      (IC(50) = 0.34 microg/ml), and may be useful for the prevention and/or treatment
      of diabetic complications.

PMID- 18711776
TI  - Rhein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma
      BEL-7402 cells.
AB  - Rhein, an anthraquinone derivative of rhubarb, inhibits the proliferation of
      various human cancer cells. In this paper, we focused on studying the effects of
      rhein on human hepatocelluar carcinoma BEL-7402 cells and further understanding
      the underlying molecular mechanism in an effort to make the potential development
      of rhein in the treatment of cancers. Using MTT assay and flow cytometry, we
      demonstrate a critical role of rhein in the suppression of BEL-7402 cell
      proliferation in a concentration- and time-dependent manner. The increase of
      apoptosis rate was observed after incubation of BEL-7402 cells with rhein at 50
      200 muM for 48 hours, and the cells exhibit typical apoptotic features including
      cellular morphological change and chromatin condensation. Moreover, rhein-induced
      cell cycle S-phase arrest. Additionally, after rhein treatment, expression levels
      of c-Myc gene were decreased, while those of caspase-3 gene were increased in a
      dose-dependent manner by using real-time PCR assay. The results demonstrate for
      the first time that cell cycle S-phase arrest is one of the mechanisms of rhein
      in inhibition of BEL-7402 cells. Rhein plays its role by inducing cell cycle
      arrest via downregulation of oncogene c-Myc and apoptosis through the caspase
      dependent pathway. It is expected that rhein will be effective and useful as a
      new agent in hepatocelluar carcinoma treatment in the future.

PMID- 18711777
TI  - An analysis of causes and treatment outcome of chronic wrist pain after distal
      radial fractures.
AB  - Healed distal radial fractures are frequently complicated by chronic wrist pain
      which is multifactorial and can be debilitating. An accurate delineation of the
      pathoanatomy is the key for successful treatment. This study reviewed 22 patients
      who had surgical treatment between 1997 and 2001 for chronic wrist pain after
      distal radial fracture. Four patterns of pathoanatomy were identified: (1) ulnar
      impaction caused by radial malunion and shortening; (2) ulnar styloid non-union;
      (3) triangular fibrocartilage complex (TFCC) tears with or without distal
      radioulnar joint (DRUJ) instability; and (4) intercarpal ligament injuries and
      chondral lesions. Surgical treatment directed towards identified abnormalities
      gave satisfactory outcome. At six months after surgery the mean functional score
      improved 36%, mean pain score decreased 50%, mean grip strength improved 25%, and
      64% of patients returned to work.

PMID- 18711778
TI  - Clinical result of operative treatment for scaphoid non-union in the skeletally
      immature: percutaneous versus open procedure.
AB  - This article is a retrospective study of 13 cases of scaphoid non-union in
      skeletally immature patients. For the fracture fixation, three cases of stable
      fibrous union with minimal sclerosis, without deformity or cystic changes were
      considered for the percutaneous Herbert screw fixation. Ten cases were managed
      with the open reduction and internal fixation with or without bone grafting. The
      average union time was 10.5 weeks post-operatively. The average union time was
      lesser in percutaneous Herbert screw fixation group (nine weeks) than open
      procedure group (11.5 weeks). All cases achieved union without any supplemental
      procedures. According to Cooney's clinical scoring, 12 cases were rated excellent
      result and one good result. The percutaneous Herbert screw fixation for scaphoid
      non-union in skeletally immature patients can be a good treatment option when it
      is fibrous union with no deformity.

PMID- 18711779
TI  - Flexor digitorum profundus avulsion of the left little finger through enchondroma
      of the distal phalanx: pull-out wire technique treatment without bone graft.
AB  - This case report describes the rare occurrence of a flexor digitorum profundus
      (FDP) avulsion of the left little finger in association with a pathological
      fracture of an enchondroma. The enchondroma was treated by simple curettage
      without bone graft. The FDP tendon was re-attached to the distal phalanx using
      the pull-out technique with a non-absorbable polyethylene suture. We recommend
      simple curettage without bone grafting in cases of enchondroma of the distal
      phalanx in which the bone defect is small.

PMID- 18711780
TI  - Endoscopic carpal tunnel release: our experience with 12,702 cases.
AB  - Carpal tunnel syndrome (CTS) is still today the most common nerve entrapment
      syndrome at the level of the upper extremity. When surgery is indicated, the
      surgical treatment of choice is the opening of the retinaculum. The authors
      describe their experience on 12,702 carpal tunnel decompressions, by the
      endoscopic procedure in a period of 14 years, outlining the indications, post
      operative treatment, complications and results.

PMID- 18711781
TI  - Delayed rupture of flexor tendons caused by protrusion of a screw head of a volar
      plate for distal radius fracture: a case report.
AB  - We report a rare occurrence of attritional rupture of flexor tendons caused by
      protrusion of the screw head of the volar radius plate. The cause of the
      protrusion was plate placement on the prominent distal volar lip of the radius
      and secondary loss of the original reduction due to using a non-locking
      osteosynthesis system for the treatment of displaced intra-articular fracture of
      the distal radius.

PMID- 18711782
TI  - Repair of the flexor pollicis longus tendon in an infant.
AB  - The author presents the case report of the rare for infant injury - the
      laceration of flexor pollicis longus tendon, which requires decisions on some
      complex questions relating to optimal tendon suture, suture material, type and
      duration of immobilisation, and the protocol for post-operative management.

PMID- 18711783
TI  - Mycobacterial tuberculous tenosynovitis of the extensor tendon occurring after
      liver transplantation: a case report.
AB  - Mycobacterial tuberculous tenosynovitis of the hand is a rare manifestation of
      extrapulmonary tuberculosis, while mycobacterial tuberculous tenosynovitis of the
      extensor tendon sheath is extremely rare. We report a case of tuberculous
      tenosynovitis of the extensor tendon of the finger, occurring in a man receiving
      immunosuppression following a liver transplantation. Symptoms improved clinically
      after conservative treatment with anti-tuberculous drugs.

PMID- 18711784
TI  - Radial perilunate trans-styloid trans-triquetrum fracture dislocation: a case
      report.
AB  - We present a rare case of radial perilunate trans-styloid fracture dislocation,
      in which the scaphoid invaginated radially into the fractured radial styloid.

PMID- 18711785
TI  - Clinical results of early active mobilisation after flexor tendon repair.
AB  - Between 2005 and 2006, ten patients with flexor digitorum profundus zone II
      injuries were included. The mean age was 41 (19-84) years. One thumb, two index,
      four middle, one ring and two little fingers were injured. Repair method
      comprised four-strand core suture and 6-0 circumferential sutures. Post-operative
      rehabilitation included immediate active extension, progressive passive full
      flexion and active hold in dorsal block splint. Follow-up was four (three to
      seven) months. Grip strength, pinch strength, ROM was 90% (70%-90%), 90% (60%
      110%) and 90% (80%-100%) of normal digit, respectively. Mayo wrist scores were
      five excellent, two good and three fair. All patients were satisfied. Compared
      with another group of ten patients with the same suture method and Kleinert
      splintage, grip strength, pinch strength and ROM were 50%, 40% and 40% of normal
      side, respectively. All differences between these two groups were statistically
      significant (p < 0.01) by paired samples T-test. There was no re-rupture.

PMID- 18711786
TI  - Asthma--air pollution may make it worse....

PMID- 18711787
TI  - . . . Infant obesity may increase the risk of developing it. . . .

PMID- 18711788
TI  - . . . And the Mediterranean Diet may decrease the risk of developing it.

PMID- 18711789
TI  - [Basic knowledge of residual chlorine].

PMID- 18711790
TI  - [Promotion of HACCP approach for the soft drink manufacturers].

PMID- 18711791
TI  - Multiple biomarkers and cardiovascular risk.

PMID- 18711792
TI  - Pursuit of an expanded physician supply.

PMID- 18711793
TI  - Pursuit of an expanded physician supply.

PMID- 18711794
TI  - Spanish farmers welcome GM maize.

PMID- 18711795
TI  - Kenya's conservation challenge.

PMID- 18711796
TI  - Darwin celebrations begin.

PMID- 18711797
TI  - Marine reserve benefits unfold.

PMID- 18711799
TI  - Obama vs McCain on global health.

PMID- 18711798
TI  - Robert A. Hinde.

PMID- 18711800
TI  - Getting to the heart of the matter in India.

PMID- 18711801
TI  - Corpo-reality.

PMID- 18711802
TI  - [Blood culture: survey of nurses' practice].

PMID- 18711803
TI  - [Malaria diagnosis: thickdrop and bloodsmear examination, and rapid test].

PMID- 18711804
TI  - [Avian influenza in human beings: epidemiological update and monitoring].

PMID- 18711805
TI  - [Management of a highly contagious patient in a Marseille Teaching Hospital].

PMID- 18711806
TI  - [Bioterrorism: reality of the threat and preparedness of medical and paramedical
      staff].

PMID- 18711807
TI  - Retraction notice to "The periosteum. Part 1. Anatomy, histology and molecular
      biology" [Injury 38 (10) (2007) 1115-1130].

PMID- 18711808
TI  - Proceedings from the 3rd International Conference on Polyphenols and Health
      (ICPH), November 25-28, 2007, Kyoto, Japan.

PMID- 18711809
TI  - Leveraging business intelligence for revenue improvement.

PMID- 18711810
TI  - "Are their babies different from ours?" Dutch culture and the Groningen Protocol.

PMID- 18711811
TI  - [Phytotherapy in complex therapy for pulmonary tuberculosis].

PMID- 18711812
TI  - [Monitoring of chemotherapy in patients with pulmonary tuberculosis by the blood
      bacteriostatic activity-determining test].
AB  - The paper gives the results of studies to determine blood bacteriostatic activity
      (BBA) in the use of a patient's autostrain and semiliquid medium versus the
      clinical and laboratory parameters of the course of a process in 101 patients
      with pulmonary tuberculosis. There is evidence for the relationship of the BBA to
      the sensitivity to isoniazid and the structure of drug resistance. The zero
      values of BBA correspond to the severest course of the disease. The efficiency of
      treatment is much higher in patients with high and moderate BBA. The latter's
      determination using the semiliquid medium permits an objective evaluation of the
      efficiency of chemotherapy, identification of patients with a poor prognosis, and
      then choice of an individual treatment regimen on day 7 after the test just
      before obtaining the data on drug sensitivity.

PMID- 18711813
TI  - [Primary drug resistance of Mycobacterium tuberculosis in adolescents with
      tuberculosis: the specific features of its clinical course, the efficiency of
      treatment].
AB  - Ninety adolescents suffering from tuberculosis with primary drug resistance (PDR)
      in Mycobacterium tuberculosis (MBT) were followed up. All the patients had
      active, marked processes, mainly infiltrative tuberculosis in the phase of decay
      and dissemination. MBT resistance to 3 drugs or more was detected in most
      patients (62.3%). Multidrug resistance was 32.2%. The course of the disease was
      chiefly favorable. An exacerbation of the process occurred during therapy in 6.6%
      of patients. In patients with PDR, abacillation occurred in 100% of cases and the
      decay cavities closed in 86.6% by the end of the course of therapy. The PDR
      patients received treatment with both first- and second-line drugs, had surgery,
      collapsotherapy, laser therapy, and physiotherapeutic treatments, and lidase.
      Treatment of patients with drug-resistant tuberculosis presents severe
      difficulties. However, good results can be achieved in most patients, by applying
      an individual approach to each patient and determining the optimum chemotherapy
      regimens and pathogenetic treatments.

PMID- 18711814
TI  - [The specific features of bacillary excretion and drug sensitivity in
      Mycobacterium tuberculosis in patients with recurrent pulmonary tuberculosis].
AB  - Data on 485 patients with recurrent pulmonary tuberculosis were studied. At the
      beginning of the study, all the patients underwent a triple sputum smear test and
      sputum was cultured in 338 cases. Among persons with a negative smear, sputum
      inoculation yielded Mycobacterium tuberculosis (MBT) in 50%. By taking into
      account these observations, bacillary excretion was detected in 72.2%. It was
      established most frequently by both methods (42%), slightly less frequently by
      the smear test (38%) and inoculation (20%). Drug resistance in MBT was revealed
      almost equally frequently in bacillary recurrences in patients with positive and
      negative sputum smear tests (68 and 62.3%, respectively). The bulk of the strains
      obtained were found to be polyresistant as well as quite often multiresistant. In
      the group of patients who had received chemotherapy by the WHO standards at
      primary detection of tuberculosis, polyresistance and multiresistance were
      encountered significantly more frequently in those who had been treated in
      previous years. The resistance of MBT to various drugs was also studied.
      Recommendations are given on the basis of the results of the study.

PMID- 18711815
TI  - [The epidemiological features of concomitance of diabetes mellitus and pulmonary
      tuberculosis].
AB  - The study was undertaken to reveal the clinical and epidemiological features of
      development diabetes mellitus (DM) and pulmonary tuberculosis (PT) in
      comorbidity. The material of the study was 143 case histories and outpatient
      cards of patients with DM and PT who were registered in 2001-2006. A total of
      11,702 cases of tuberculosis were notified in 1999-2005. The significance ofa
      difference between the extensive indices was assessed by Student's test preceded
      by the Fisher angular transformation. Thus, the specific features of development
      of DM and PT are: 1) type 1 DM frequently occurs in youth while type 2 DM does at
      mature age; 2) tuberculosis in DM patients occurs at mature and old ages; 3)
      there is a male preponderance among patients with type 1 DM and a female
      predominance among those with type 2 DM; 4) comorbidity is more common in town
      dwellers; 5) severe PT was prevalent in type 1 DM; mild PT is rarely observed in
      type 2 DM; 6) in comorbidity, fibro-cavernous, cirrhotic tuberculosis, caseous
      pneumonia, and tuberculoma are encountered by several times more frequently and
      focal tuberculosis and tuberculous pleurisy are less frequently in patients
      without DM.

PMID- 18711816
TI  - [Surgical science].

PMID- 18711817
TI  - [Will continuous patient questioning bring an economic and qualitative benefit
      for your practice clinic?].

PMID- 18711818
TI  - [Daily thrombocyte count in low molecular weight heparin treatment].

PMID- 18711819
TI  - [Surgical graduate education in crisis].

PMID- 18711820
TI  - [Trusting the assistant... sovereign physician leadership style].

PMID- 18711821
TI  - [Specialist status privilege of medical providers. 5: General practice relevant
      examples].

PMID- 18711822
TI  - [Court decides practice value in contract general practice--Price agreement
      between buyer and seller irrelevant!].

PMID- 18711823
TI  - [Mesothelioma in academics. German Bochum mesothelioma register].

PMID- 18711824
TI  - [Association of epilepsy and headache from the patient perspective].
AB  - Headache occurs more frequently in patients with epilepsy as compared to the
      general population. Current studies in patients with epilepsy and migraine show
      that this increased frequency is independent of the seizure type, etiology or age
      at onset. People with epilepsy are 2.4 times more likely to be diagnosed with
      migraine. In our study, we evaluated patients' attitudes toward comorbidity of
      epilepsy and all headache types. Study results showed a significant number of
      patients to have experienced headaches after being diagnosed with epilepsy, and
      some of them assumed it was a side effect of their antiepileptic drug. Based on
      these data, we propose a more detailed assessment of the history of epilepsy
      including questions on headache, and offer the epilepsy patient a newer
      antiepileptic drug. In this way, we can significantly decrease the comorbidity of
      these two neurologic disorders and improve the quality of life in epilepsy
      patients.

PMID- 18711826
TI  - [Drug information--national decision needed].

PMID- 18711827
TI  - [Levander is so right: outpatient care with special conditions is an
      objectionable proposal].

PMID- 18711828
TI  - [Water--no support for the "8x8 rule"].

PMID- 18711829
TI  - Scanning for hidden heart disease.

PMID- 18711831
TI  - The future looks brighter for corneal transplants.

PMID- 18711830
TI  - Weight loss surgery puts diabetes in remission.

PMID- 18711832
TI  - At risk for Alzheimer's?  Who wants to know?

PMID- 18711833
TI  - The patient information that came with my Viagra prescription warned of sudden
      vision or hearing loss.  Should I be worried?

PMID- 18711834
TI  - The first 24 hours of the World Trade Center attacks of 2001--the Centers for
      Disease Control and Prevention emergency phase response.
AB  - On 11 September 2001, terrorists hijacked two passenger planes and crashed them
      into the two towers of the World Trade Center (WTC) in New York City. These
      synchronized attacks were the largest act of terrorism ever committed on US soil.
      The impacts, fires, and subsequent collapse of the towers killed and injured
      thousands of people. Within minutes after the first plane crashed into the WTC,
      the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia,
      initiated one of the largest public health responses in its history. Staff of the
      CDC provided technical assistance on several key public health issues. During the
      acute phase of the event, CDC personnel assisted with: (1) assessing hospital
      capacity; (2) establishing injury and disease surveillance activities; (3)
      deploying emergency coordinators/liaisons to facilitate inter-agency coordination
      with the affected jurisdictions; and (4) arranging rapid delivery of emergency
      medical supplies, therapeutics, and personal protective equipment. This incident
      highlighted the need for adequate planning for all potential hazards and the
      importance of interagency and interdepartmental coordination in preparing for and
      responding to public health emergencies.

PMID- 18711835
TI  - Seen but not heard: injuries and deaths from landmines and unexploded ordnance in
      Chechnya, 1994-2005.
AB  - INTRODUCTION: Due to more than a decade of armed conflict and civil unrest,
      Chechnya is among the regions most affected by landmines and unexploded ordnance
      worldwide. HYPOTHESIS: The study was performed to assess the magnitude of
      injuries and deaths due to landmines and unexploded ordnance in Chechnya between
      1994 and 2005 and to describe epidemiologic patterns and risk factors for these
      events. METHODS: Surveillance data that included 3,021 civilian non-combatants
      injured by landmines and unexploded ordnance in Chechnya during 1994-2005 were
      analyzed. Local non-governmental organizations in collaboration with the United
      Nations Children's Fund conducted victim data collection using trained staff to
      interview victims or their families. Surveillance data were used to describe
      injury trends, victim demographics, injury types, risk behaviors, and types of
      explosives related to landmine and unexploded ordnance events. RESULTS: The
      largest number of injuries occurred in 2000 (716, injury rate 6.6 per 10,000) and
      2001 (640, injury rate 5.9 per 10,000). One-quarter of all victims were younger
      than 18 years, and 19% were females. The case-fatality rate was 23%.
      Approximately 40% of victims were injured by landmines, 30% by unexploded
      ordnance, and 7% by booby traps. A large proportion of children and adults were
      injured while traveling or performing activities of economic necessity; 29% of
      children were injured while tampering with explosives or playing in a
      contaminated area. The proportion of victims with lower limb amputations was
      similar among children and adults (14% and 17%, respectively), whereas the
      proportion ofvictims with upper limb amputations was three times higher in
      children than in adults (12% and 4%, respectively). Most accidents that occurred
      while the victim was traveling or performing activities of economic necessity
      were caused by landmines, while most accidents that occurred while the victim was
      playing near an explosive device or tampering with it were caused by unexploded
      ordnance. CONCLUSIONS: Civilians in Chechnya experienced the highest rates of
      injury from landmines and unexploded ordnance ever documented, 10 times higher
      than injury rates reported from such highly affected countries as Afghanistan,
      Angola, or Cambodia. Urgent efforts to identify, mark, and clear mined areas
      and/or areas contaminated with unexploded ordnance are needed to prevent further
      civilian injuries and deaths.

PMID- 18711837
TI  - Issues and trends in American Annals of the Deaf publication. 2001 to 2007.

PMID- 18711838
TI  - Educational programs for deaf students. Schools and programs in the United
      States.

PMID- 18711840
TI  - Educational programs for deaf students. Postsecondary programs.

PMID- 18711839
TI  - Educational programs for deaf students. Schools and programs in Canada.

PMID- 18711841
TI  - University and college programs for personnel in deafness.

PMID- 18711842
TI  - Programs for deaf-blind children and adults.

PMID- 18711843
TI  - Advocacy,  support, and rehabilitation programs.

PMID- 18711844
TI  - Research on deafness. Doctoral dissertations.

PMID- 18711845
TI  - Gendering the revolution: language, politics, and the birth of a nation (1789
      1795).

PMID- 18711846
TI  - [Federico Gravina sent ashore in 1795 due to illness].

PMID- 18711847
TI  - Nursing home optometry: improving the quality of life.

PMID- 18711849
TI  - Changing office procedures can grow profits.
AB  - Having patients choose frames before their examinations can increase revenues.

PMID- 18711850
TI  - Gender and the shifting ground of revolutionary politics: the case of Madame
      Roland.

PMID- 18711851
TI  - HIPAA Privacy Rule: 33,000 complaints, no fines.
AB  - The AOA Office of Counsel provides a review of recent reports, advisories, and
      court actions pertinent to the practice of eye and vision care.

PMID- 18711852
TI  - The CMS online manual system.
AB  - The U.S. Centers for Medicare & Medicaid Services (CMS) explains how health care
      providers can use the Web-based CMS Online Manual System to learn about the
      Medicare program and stay up to date with the latest program changes.

PMID- 18711853
TI  - Neurogenic vestibular evoked potentials in multiple sclerosis patients.

PMID- 18711854
TI  - An advance against acne. A vacuumlike device is defeating some really tough
      cases.

PMID- 18711855
TI  - [Autonomy in private practice instead of heteronomy].

PMID- 18711860
TI  - Store-operated Orai1 and IP3 receptor-operated TRPC1 channel.
AB  - Store-operated channels (SOC) are known to be physiologically activated following
      agonist-induced IP3 production and depletion of Ca2+ stores. Here we present
      molecular,biophysical and mechanistic evidence that two ubiquitously expressed
      plasma membrane channels may be responsible for creating a complex and sometimes
      controversial SOC image: one being a real SOC encoded by Orai1 and activated
      exclusively upon depletion of Ca2+ stores (via iPLA2beta -dependent pathway),
      while the second one is an IP3 receptor-operated channel (IP3ROC) encoded by
      TRPC1 and activated via its conformational coupling with IP3 receptor. In RBL-2H3
      cells endogenously expressing Orai1 and TRPC1, we unmasked and characterized
      whole-cell current through IP3ROC channels that was hiding behind some familiar
      fingerprints of ICRAC, a current through the classical Ca2+-selective SOC (CRAC)
      channels. We discriminated these currents by their molecular identity,
      selectivity and different requirements for store depletion, IP3, iPLA2beta and
      conformational coupling to IP3 receptor. New knowledge on the properties and
      coexistence of Orai1-encoded SOC and TRPC1-encoded IP3ROC, and the use of
      experimental approaches introduced in this manuscript should help avoid further
      confusion about these channels, and open new exciting possibilities for their
      independent studies

PMID- 18711861
TI  - [The medical staff of the royal military school at Effiat, 1776-93].

PMID- 18711862
TI  - Tea and opium: some further notes on Macartney's role.

PMID- 18711863
TI  - The rise and fall of Emanuel Mendes da Costa: a severe case of the "philosophical
      dropsy"?

PMID- 18711865
TI  - [A fragile industry: sugar refining in Lille, 1675-1790].

PMID- 18711867
TI  - Female relationships in early modern England.

PMID- 18711868
TI  - Massive haemorrhage following penetrating abdominal trauma.

PMID- 18711869
TI  - A very unusual case history.
AB  - The above case history demonstrates well how a severe potentially lethal medical
      condition can often develop quite insidiously with what appeared to be quite
      common and everyday symptoms initially. In my opinion, one of the potential
      problems with the management of this lady was the number of different doctors she
      consulted within the practice, both military and locum (11 in total during 2007)
      resulting in lack of continuity of case. However, it is impossible to ascertain
      quite when the vasculitis actually developed or whether it could have been
      suspected earlier. In nearly 30 years as a doctor, this is the first case of
      Wegener's that I have knowingly come across. Perhaps because of such rarities,
      this is what makes being a GP such an interesting and challenging role. So next
      time you see someone with a runny nose and dry cough .... think again!

PMID- 18711870
TI  - Anaesthesia in the Armed Forces--a history of the Triservice Apparatus.

PMID- 18711871
TI  - Pulmonary fitness for underwater pressure exposure: a review of current
      procedures and standards.
AB  - The PFT SOPs developed by the DD&HM provide a standardised framework by which
      individuals requiring PFTs for service occupational reasons receive co-ordinated
      administration, consistent medical opinion and the opportunity to provide
      feedback. The SOPs have built in audit standards to ensure clinical governance is
      maintained.

PMID- 18711872
TI  - Major medical incident--a nurse's tale.

PMID- 18711873
TI  - Operation Telic--a personal view.

PMID- 18711875
TI  - Hyperbaric therapy outside of dentistry.

PMID- 18711874
TI  - Quantitative evaluation of variance in secondary dentition eruption among ethnic
      groups in Hawai'i.
AB  - Though little scientific evidence existed to support the belief among dentists
      who treat Pacific Islander populations that many children of the region erupt
      secondary teeth earlier and at an eruption rate which exceeds Caucasian children.
      Based upon a data set created in Hawai'i during the 1998-1999 school year, of
      26,097 public school children, the opportunity presented itself to examine for
      variance in eruption timing and sequence. Hawai'i is an ethnic diverse community,
      with a majority population comprised of Asians and Pacific Islanders. Children, 5
      through 9 years of age, were examined for gender and ethnic variance. In the
      aggregate, at all ages, girls erupted teeth earlier than boys, however, while
      generally true among individual tooth types, that variance was not always
      statistically significant. By ethnic group, African Americans exhibited earlier
      eruption by contrast with Caucasians, however, Caucasian children caught up by
      nine years of age. Native Hawaiian, Samoan and Tongan children exhibited earlier
      and high rates of secondary dentition eruption than Caucasian or African American
      children. Children of various Asian cohorts did not exhibit significant variance
      by contrast with Caucasians. Based upon these findings, the authors recommend
      that dietary fluoride supplementation of Native Hawaiian, Samoan and Tongan
      children begin at birth rather than six months of age and that these children be
      targeted for pit & fissure sealants as early as five years of age.

PMID- 18711876
TI  - Can your company survive a disaster?

PMID- 18711877
TI  - New ESRD clinical performance measures and data collection system: progress and
      pitfalls.

PMID- 18711878
TI  - Tired of getting schooled by health insurers, the AMA issues its first report
      card to cut costs.

PMID- 18711879
TI  - Risk factors affecting nutritional status of dialysis patients: a quality
      improvement project.
AB  - People with chronic kidney disease on dialysis are at very high risk for protein
      energy malnutrition (PEM). It is well documented that malnourished patients have
      increased frequency of hospital admissions, longer hospital stays, lower quality
      of life, and increased risk of death. Serum albumin level is a valid measure for
      nutritional status of PEM. Clinical practice guidelines for nutrition,
      established by the National Kidney Foundation's Kidney Disease Outcomes Quality
      Initiative (KDOQI), recommend that patients on dialysis achieve an albumin of 3.7
      g/dL (BCP) to ensure optimal nutrition and decrease risks of PEM. At Mercy
      Dialysis Center, it was determined that only 6% (n=97) of patients at Mercy
      Dialysis Center met this recommended albumin level. This led to an extensive
      continuous quality improvement project to improve these results. The
      nephrologist, nurse practitioner, dietitian, social worker, nurses, and dialysis
      technicians all contributed to this team project. PROJECT SUMMARY: Eleven risk
      factors for low serum albumin levels were identified. All patients at Mercy
      Dialysis Center were assessed for each risk factor. Interventions were
      implemented to reduce these risks. Serum albumin levels were tracked at the
      beginning of our study, at six months, and at one year on all patients. RESULTS:
      At the end of the study, 36% of the patients met the KDOQI recommendations for
      serum albumin levels (compared to only 6% prior to the project), and albumin
      levels overall improved. The risk factors that affected our patients the most
      included: dentition, infections or sepsis, multiple medications, and pain. It was
      determined that these, and all other risk factors had an impact on the
      nutritional status of our patients and need to be addressed on a regular basis.

PMID- 18711880
TI  - DaVita reaches out to non-renal groups.

PMID- 18711882
TI  - Moderate growth seen among large providers in 2007-08.

PMID- 18711881
TI  - Perspectives on vitamin D therapy in chronic kidney disease.

PMID- 18711883
TI  - CROWNWeb: the evolution of kidney data management. 2.
AB  - The Centers for Medicare & Medicaid Services is developing a Web-based
      application, CROWNWeb, which is designed to update mandated electronic data entry
      and retrieval for dialysis facilities nationwide. Part 2 of this three-part
      series introduces CROWNWeb to the ESRD community. It discusses the release and
      impact of the recently released ESRD Conditions for Coverage, and provides an
      overview of the CMS CROWNWeb system, highlighting features and functionality.

PMID- 18711884
TI  - Out-of-network payments for ESRD care: the National Renal Alliance case.

PMID- 18711885
TI  - Do as I say, not as I do.

PMID- 18711886
TI  - Health for life. Your lifestyle, your genes, and cancer.

PMID- 18711887
TI  - Health for life. The doctor factor. Doctors and patients who battle cancer
      together can develop a unique bond: corned beef on chemo day.

PMID- 18711888
TI  - 'Some kids do die'. How a pediatric oncologist balances reality and optimism. The
      banjo helps.

PMID- 18711889
TI  - Health for life. Medical report card. The battle against cancer.

PMID- 18711890
TI  - Health for life. A deadly disparity. Blacks are more likely than whites to die of
      breast and prostate cancer. Researchers want to know why.

PMID- 18711891
TI  - Health for life M.D. Advice for survivors. A Harvard doctor who has battled
      breast cancer herself tackles the challenges of life after treatment.

PMID- 18711892
TI  - Site under construction. As a trio of states lower the CON barriers to building
      hospitals, others are studying a variety of reforms to promote competition.
AB  - CON reforms were approved in Florida, Georgia and Iowa this year, and other
      states are also looking at ways to promote competition. While some observers
      don't see a move to sweeping change, it's a trend that draws applause. "There's
      no plausible argument that certificate of need meets its intended purpose.
      Instead, it denies access and it denies choice," says consultant Robert James
      Cimasi, left!

PMID- 18711893
TI  - Minn.: let's reform. Financing, delivery overhaul out.

PMID- 18711894
TI  - Bidding battle. Objections grow to CMS' competitive bidding project.

PMID- 18711895
TI  - 'Ready to fire up'. January 2009 launch for Prometheus.

PMID- 18711896
TI  - Price check on Empire. KPMG to evaluate Community's buy.

PMID- 18711897
TI  - Doc owners caught in bind. Kansas court rules dual investors violated bylaws.

PMID- 18711898
TI  - Casey links MedCath, Eclipsys.

PMID- 18711900
TI  - My year inside Maimonides. A hospital with a polyglot patient body learns the
      importance of communication.

PMID- 18711901
TI  - The rise of foreign agents. Drugs and other medical products from offshore
      suppliers can offer tremendous savings, but safety has become an increasing
      concern.

PMID- 18711902
TI  - A hospital on the march. U.S. Army uproots and upgrades its South Korean medical
      operations.

PMID- 18711903
TI  - Midwest raises the bar. 100 Top Hospitals winners' balanced performance drives
      safety to new heights.

PMID- 18711904
TI  - POA coding challenges. Concern grows over quality of documentation.

PMID- 18711905
TI  - The way to the top. High marks coincide with quality patient-safety measures.

PMID- 18711906
TI  - Hospital race across Rio Grande. Three providers tussle for Albuquerque's growth
      area.

PMID- 18711907
TI  - Collection urgency. Tenet-based startup to help with self-pay accounts.

PMID- 18711908
TI  - Leading the way. One doc group not resisting e-Rx.

PMID- 18711909
TI  - Humana exec joins board. DexCom appointment worth $330,000 over three years to
      Jonathan Lord.

PMID- 18711910
TI  - AAFP's conversion. TransforMED's for-profit switch.

PMID- 18711911
TI  - The other big workforce shortage. As laboratory technology wanes as a career
      choice, a staffing crisis grows.

PMID- 18711912
TI  - A primary-care pilot. The medical home passes a test in the West.

PMID- 18711913
TI  - Beyond the hospital. More nurses are working outside hospitals, and the need is
      growing.

PMID- 18711914
TI  - Workforce report 2008. Where have all the nurses gone?

PMID- 18711915
TI  - By the numbers. Health systems with largest number of full-time employees.

PMID- 18711917
TI  - [Health in all aspects].

PMID- 18711916
TI  - [The 24/7 health society].

PMID- 18711918
TI  - [Development of a systematically approached guard station].

PMID- 18711919
TI  - [Between the Canton hospital and the Black Forest clinic].

PMID- 18711920
TI  - [Risk and unexpected entry into life].

PMID- 18711921
TI  - [Too little for life, too much for death].

PMID- 18711922
TI  - [Types of nurses: the warriers].

PMID- 18711923
TI  - [A change is about to happen, but where should one go?].

PMID- 18711924
TI  - [New writings in the future of systems].

PMID- 18711925
TI  - [Welcome to cafe-philosophy nurses!].

PMID- 18711926
TI  - [Interactions and reflexes].

PMID- 18711927
TI  - [The nurse, the confidentiality and 'the secret'].

PMID- 18711928
TI  - [The nurse as mentor: to listen, ito integrate and to accompany].

PMID- 18711929
TI  - [The nursing profession: a voice that cannot be distorted?].

PMID- 18711930
TI  - [And if we prove that the delivery was fundamental?].

PMID- 18711931
TI  - ["And so, can you tell me what you want me to do?"].

PMID- 18711932
TI  - Editor's choice June 2008.

PMID- 18711933
TI  - Global and regional annual 'new case detection' of leprosy reported by World
      Health Organization.

PMID- 18711934
TI  - Global themes in international public health.

PMID- 18711935
TI  - Interviews with two key leaders in leprosy: Professor PL Joshi and Professor
      Maria Leide.

PMID- 18711937
TI  - A qualitative study of common functional problems experienced by people with
      complete ulnar nerve paralysis.
AB  - OBJECTIVES: To identify the most common functional problems caused by ulnar nerve
      palsy. This study is the first phase in the process of developing a patient
      centred hand function questionnaire specific for ulnar palsy. DESIGN: Twenty-five
      participants with complete irreversible ulnar nerve palsy were asked to record
      the five main problems they had because of their hand deformity in the week
      before they came to hospital. They ranked these problems in order of priority.
      The participants had all been referred to LEPRA-HOINA Leprosy Reconstructive
      Surgery Hospital, Muniguda, Orissa, India for tendon transfer surgery. RESULTS:
      Thirty-nine problems were experienced by the participants; 37 of these were
      functional problems. Five problems had a prevalence of > or =40%, these were
      holding soap (68%), eating (56%), buttoning (48%), holding a glass (44%) and
      lifting small objects (44%). Further analysis according to whether the left or
      right hand was affected was performed; 92% of participants with right ulnar nerve
      palsy had a problem eating compared to only 20% of those with left ulnar palsy.
      Eating was ranked as the most important problem by 28% of participants, holding a
      glass by 12% and holding soap by 8%. CONCLUSIONS: Ulnar nerve palsy had an
      important impact on basic activities of daily living--eating, washing, and
      drinking. Not only are these activities themselves affected but the person with a
      hand deformity avoids social situations where it will be noticed. This study
      indicates that there is a need to identify and treat people who have ulnar nerve
      palsy in order that they can be integrated into society, become independent with
      activities of daily living and earn an income.

PMID- 18711936
TI  - The effect of corticosteroid usage on the bacterial killing, clearance and nerve
      damage in leprosy: a prospective cohort study: part 1--study design and baseline
      findings of 400 untreated multibacillary patients.
AB  - OBJECTIVE: To investigate possible adverse effects of therapeutic usage of
      corticosteroids on the killing and clearance of M. leprae and the clearance of
      granuloma, in patients with multibacillary (MB) leprosy. DESIGN: A cohort of 400
      untreated MB patients were sub-grouped into those to be treated with
      corticosteroids (prednisolone 40 mg daily tapered to 5 mg over 12 weeks) along
      with MB-MDT for reaction and/or neuritis or silent neuropathy (SN) of <6 months
      duration (group A), and those with no reaction and to be treated with MDT only
      (group B). Clinical, bacteriological, histopathological and neurological test
      findings at fixed time points were compared. Analysis was performed using SPSS
      version 10.0. The significance of association was tested using Chi-square test.
      In the current report, we describe the study design and baseline findings of 400
      untreated MB patients, with special emphasis on differences between patients in
      groups A and B. RESULTS: At baseline, applying Ridley-Jopling classification, 39%
      patients were BT, 20% BB, 24% BL, 12% sub-polar LL and 5% pure neural (PN).
      Overall, 60% patients were slit skin smear (SSS) negative and 33% presented with
      disability either grades 1 or 2. Overall 140/400 (35%) patients presented with
      reaction and/or neuritis and 11/400 (3%) presented with SN of <6 months duration.
      Comparing groups A and B, the percentage of patients presenting with DG2 was
      significantly higher in group A (43%). By clinical tests, monofilaments (MF) and
      voluntary muscle testing (VMT), the percentage of patients and nerves showing
      functional impairment was also significantly higher in group A. However, in the
      more sensitive nerve conduction velocity (NCV) test, the percentage of patients
      that showed nerve abnormalities was closely comparable; 94% and 91% in groups A
      and B respectively while number of affected nerves was higher in group A.
      CONCLUSION: At baseline, as recorded by NCV, peripheral nerve function
      abnormality was observed in almost all the MB patients regardless of reaction;
      but among those presenting with reaction or neuritis, the nerve damage was more
      severe and extensive.

PMID- 18711938
TI  - A comparison of ML Flow serology and slit skin smears to assess the bacterial
      load in newly diagnosed leprosy patients in Brazil.
AB  - INTRODUCTION: The ML Flow test is an immunochromatographic assay that detects IgM
      antibodies against M. leprae-specific anti-phenolic glycolipid I (PGL-I). In
      addition to slit skin smears stained by the Ziehl-Neelsen technique, it can be
      helpful in the operational classification of leprosy patients for treatment
      purposes. OBJECTIVE: This work studied the relationship between antibody levels
      as detected by semi-quantitative ML Flow serologic test and bacterial load as
      quantified by slit skin smear. PATIENTS AND METHODS: 135 patients with newly
      detected leprosy at the reference service in Sanitary Dermatology in Brazil had
      slit skin smears (registered as bacillary index - BI) and an ML Flow test
      (registered qualitatively and semi-quantitatively) performed at admission. A
      logistic regression and agreement measures (kappa index) were calculated.
      RESULTS: Slit skin smears were positive in 35.9% of patients and 57% of patients
      were seropositive for PGL-1 antibodies. Among the seropositive patients, 416% had
      five or fewer skin lesions, and 65.8% had more than one peripheral nerve
      involved. Slit skin smears were positive in only three seronegative patients
      (5.6%), and negative in 41.9% of seropositive patients. Patients with a BI of 4 +
      had an OR of 33 for being seropositive in comparison to those with a low BI.
      CONCLUSIONS: There is a correlation between serologic test and slit skin smear
      results. Therefore, an ML Flow test may become a useful tool in the clinical
      classification of leprosy, besides slit skin smears, which require a proper
      laboratory infrastructure and experienced personnel.

PMID- 18711939
TI  - An evaluation of the Sinan health information system as used by the Hansen's
      disease control programme, Pernambuco State, Brazil.
AB  - BACKGROUND: Since the introduction of the national notifiable diseases
      information system (SINAN) in Pernambuco State, Brazil, in 1994, many problems
      have been encountered. The aim of this study was to evaluate the SINAN software,
      quality of data input, the transfer of the computerised data from the
      municipality to state levels, human resources and other factors associated with
      the health information system infrastructure (HIS). METHODS: A cross-sectional
      study was carried out in Pernambuco state, North-eastern Brazil, in 2005. A
      sample of health regions and municipalities was chosen. SINAN forms from those
      municipalities were analysed and the flow of notifications followed from
      municipal level to the regional and finally to the state. Professionals from
      health units, district, municipal and regional Hansen's Disease Control Programme
      (HDCP) and Epidemiological Surveillance System (ESS) coordinators, health
      secretaries and managers of the municipalities and health regions selected were
      interviewed. RESULTS: SINAN software is functioning up to expectation. However,
      at all levels of the health system, serious weaknesses not related to the SINAN
      software were found, varying from lack of human resources (limited number of
      staff and staff development), lack of infrastructure (office space, computers,
      supplies, etc.) to an absence of effective coordination, management and
      supervision of the HIS. CONCLUSIONS: Lack of reliable, complete and timely
      information, and especially the lack of widespread analysis and use of available
      information in planning and management of health services were the main
      weaknesses found. Many areas need urgent attention: the quality of patient
      examination, recording and reporting, the timely processing of quality data, the
      coordination and management of disease control programmes, and the use of HIS
      reports by the health services and health managers. Regular feedback, supportive
      supervision visits and annual reviews are essential to monitor the system and
      make sure that essential information is decentralised and used by the primary
      health services and HDCP coordination. Assessing the quality of services from a
      client perspective would give additional information for the identification of
      strengths and weaknesses of the Hansen's disease (leprosy) services.

PMID- 18711940
TI  - A clinical and radiological follow-up study in leprosy patients with asymptomatic
      neuropathic feet.
AB  - OBJECTIVES: An MRI study done in 2000 on 10 leprosy patients with neuropathic
      feet, without clinical complications such as ulcerations, osteomyelitis or
      Charcot deformities revealed abnormalities in nine patients, with degradation,
      interruption of subcutaneous fat and effusion/synovitis, all located in the first
      metatarsophalangeal (MTP) region. Since these MRI abnormalities may precede
      clinical complications of the foot, a follow-up study was performed. DESIGN: A
      new evaluation was based on a clinical examination and an MRI of the same
      patients who participated in the initial study. RESULTS: Four patients were lost
      to follow-up. Average follow-up period was 4-6 years. MRI abnormalities in the
      MTP 1 region in the first study were no longer visible in three patients, but
      were still present in two patients. In six patients new MRI findings were found,
      without clinical evidence of ulceration, osteomyelitis or Charcot deformity. No
      relationship was found between MRI findings in the MTP 1 region at the start of
      the study and the development of foot ulcers, callus or skin fissures in the MTP
      1 region during follow-up. CONCLUSION: MRI findings of interruption and
      infiltration of the subcutaneous fat in leprosy patients with uncomplicated
      neuropathic feet do not necessarily have any clinical implication for the
      development of future foot problems.

PMID- 18711941
TI  - A case report of venous thrombosis in a leprosy patient treated with
      corticosteroid and thalidomide.
AB  - Thalidomide is the drug of choice in the treatment of severe erythema nodosum
      leprosum (ENL) in men. It has recently been associated with deep venous
      thrombosis (DVT) when used in treatment of refractory multiple myeloma along with
      combination chemotherapy. We report a case of DVT in a patient treated for ENL
      with corticosteroids and thalidomide, and suggest a possible mechanism for the
      association.

PMID- 18711942
TI  - Mycobacterial infections causing cutaneous disease; or how is leprosy
      transmitted?

PMID- 18711943
TI  - Dr. Noshir Antia, FRCS (Eng.) FACS (Hon.).

PMID- 18711944
TI  - Improving care for patients with serious mental illness.

PMID- 18711945
TI  - Treatment options for patients with Bell's palsy.

PMID- 18711946
TI  - Arthroscopic surgery for knee osteoarthritis.

PMID- 18711947
TI  - Cranberry products for treatment of urinary tract infection.

PMID- 18711948
TI  - Spontaneous vaginal delivery.
AB  - Vaginal delivery is a natural process that usually does not require significant
      medical intervention. Management guided by current knowledge of the relevant
      screening tests and normal labor process can greatly increase the probability of
      an uncomplicated delivery and postpartum course. All women should be screened for
      group B streptococcus; women who test positive should be treated with antibiotics
      during labor. Routine human immunodeficiency virus screening of all pregnant
      women, and treatment with antiretroviral medication for those who test positive,
      can reduce perinatal transmission of the infection. Once a woman is in labor,
      management should focus on the goal of delivering a healthy newborn while
      minimizing discomfort and complications for the mother. In a patient who tests
      negative for group B streptococcus, delaying admission to the labor ward until
      she is in active labor decreases the number of possible medical interventions
      during labor and delivery. Once a patient has been admitted to the hospital,
      providing her with continuous emotional support can improve delivery outcomes and
      the birthing experience. Epidural analgesia is effective for pain control and
      should not be discontinued late in labor to reduce the need for operative vaginal
      delivery. Epidurals prolong labor, but do not increase the risk of cesarean
      delivery. Research has shown that labor may not progress as rapidly as
      historically reported; this should be considered before intervening for dystocia.
      Routine episiotomy increases morbidity and should be abandoned. Once the infant
      has been delivered, active management of the third stage of labor decreases the
      risk of postpartum hemorrhage.

PMID- 18711949
TI  - Information from your family doctor. Labor and delivery: what you should know.

PMID- 18711950
TI  - Radiologic evaluation of hematuria: guidelines from the American College of
      Radiology's appropriateness criteria.
AB  - Hematuria, symptomatic and incidental, that involves more than three red blood
      cells per high-power field on two of three properly collected urinalysis
      specimens warrants some type of imaging to evaluate the upper tracts.
      Traditionally, excretory urography or the intravenous pyelogram has been the
      mainstay of the hematuria work-up, but computed tomography urography has more
      recently been recognized to have significant advantages. Multidetector computed
      tomography urography, a cross-sectional technique, is less susceptible to
      overlying bowel gas and more sensitive for detection of small tumors and calculi.
      Moreover, intravenous-pyelogram-like images can be obtained by using
      reconstruction techniques. In specific cases, ultrasound examination and magnetic
      resonance imaging can also be useful, and are particularly helpful in children
      and pregnant women. Neither modality has the sensitivity of computed tomography
      for calculi, but small tumors may be visible on magnetic resonance imaging. This
      article reviews the appropriateness criteria for the various radiologic imaging
      tests used in the evaluation of hematuria, as proposed by the American College of
      Radiology.

PMID- 18711951
TI  - Primary care issues in patients with mental illness.
AB  - Family physicians commonly care for patients with serious mental illness.
      Patients with psychotic and bipolar disorders have more comorbid medical
      conditions and higher mortality rates than patients without serious mental
      illness. Many medications prescribed for serious mental illness have significant
      metabolic and cardiovascular adverse effects. Patients treated with second
      generation antipsychotics should receive preventive counseling and treatment for
      obesity, hyperglycemia, diabetes, and hyperlipidemia. First- and second
      generation antipsychotics have been associated with QT prolongation. Many common
      medications can interact with antipsychotics, increasing the risk of cardiac
      arrhythmias and sudden death. Drug interactions can also lead to increased
      adverse effects, increased or decreased drug levels, toxicity, or treatment
      failure. Physicians should carefully consider the risks and benefits of second
      generation antipsychotic medications, and patient care should be coordinated
      between primary care physicians and mental health professionals to prevent
      serious adverse effects.

PMID- 18711952
TI  - Information from your family doctor. Mental illness: taking care of yourself.

PMID- 18711953
TI  - Choosing a skeletal muscle relaxant.
AB  - Skeletal muscle relaxants are widely used in treating musculoskeletal conditions.
      However, evidence of their effectiveness consists mainly of studies with poor
      methodologic design. In addition, these drugs have not been proven to be superior
      to acetaminophen or nonsteroidal anti-inflammatory drugs for low back pain.
      Systematic reviews and meta-analyses support using skeletal muscle relaxants for
      short-term relief of acute low back pain when nonsteroidal anti-inflammatory
      drugs or acetaminophen are not effective or tolerated. Comparison studies have
      not shown one skeletal muscle relaxant to be superior to another. Cyclobenzaprine
      is the most heavily studied and has been shown to be effective for various
      musculoskeletal conditions. The sedative properties of tizanidine and
      cyclobenzaprine may benefit patients with insomnia caused by severe muscle
      spasms. Methocarbamol and metaxalone are less sedating, although effectiveness
      evidence is limited. Adverse effects, particularly dizziness and drowsiness, are
      consistently reported with all skeletal muscle relaxants. The potential adverse
      effects should be communicated clearly to the patient. Because of limited
      comparable effectiveness data, choice of agent should be based on side-effect
      profile, patient preference, abuse potential, and possible drug interactions.

PMID- 18711954
TI  - Sudden onset of right lower quadrant pain after heavy exercise.

PMID- 18711955
TI  - FPIN's clinical inquiries. Antiepileptic drug level monitoring.

PMID- 18711956
TI  - Ethical considerations of patients with pacemakers.

PMID- 18711957
TI  - [The analysis of incidence of selected types of birth defects in the Czech
      Republic according to a multiplicity of pregnancy].
AB  - OBJECTIVE: To analyze an occurrence of selected types of birth defects in single
      and multiple pregnancies in the Czech Republic in 1994-2006 period. DESIGN: A
      retrospective epidemiological analysis of birth defects according to a
      multiplicity of pregnancy. SETTING: Department of Medical Genetics, Thomayer's
      University Hospital, Prague. Chair of Medical Genetics, Postgraduate Medical
      Institute, Prague. METHODS: Data were collected from National Birth Defects
      Register (Institute of Health Information and Statistics). Incidences of selected
      types of birth defects according to pregnancy multiplicity were analyzed.
      RESULTS: In 1994-2006, totally 1 132 567 children were born in the Czech
      Republic, out of which more than 42 000 with a birth defect. In all particular
      defects, incidences were increased in children born from multiple pregnancies
      compared to singletons. CONCLUSION: Highest differences in birth defects
      incidences in children born from single versus multiple pregnancies were found in
      neural tube defects group and in congenital hydrocephalus.

PMID- 18711958
TI  - [Cervical cerclage. Results of the last ten year period (1997-2008) in Faculty
      Hospital Olomouc].
AB  - OBJECTIVE: To evaluate the effectiveness of the cervical cerclage in the last ten
      year period on pregnancy outcome. STUDY DESIGN: Retrospective study. SETTING:
      Gynaecological and Obstetric Clinic Medical Faculty Palacky University and
      Faculty Hospital Olomouc. METHODS: In the retrospective analysis of maternal and
      newborn records in the ten year period from 1.1. 1998 to 31. 12. 2007 were
      identified three groups of indications for operative cervical closure: elective-
      on the basis of history without objective evidence of cervical change, emergency
      cerclage--with objective manifestation of cervical insufficiency and rescue
      cerclage of a widely dilated cervix with prolapsed unruptured membranes. RESULTS:
      A total 102 patients underwent cerclage between 11 and 31 weeks gestation. The
      prevalence of operative intervention was 0.6% of all mothers. Cervical cerclage
      was done by the McDonald technique. 17 patients had elective operations, 57
      emergency and 28 rescue cerclage. Median length of interval from cerclage to
      delivery was significantly shorter after rescue cerclage, 26 days, (range 2-126)
      compared to emergency cerclage patients, 74 days (range (7-148). (P = 0,000005).
      Median interval from cerclage to delivery in elective operation was 105 days
      (range 9-188). Newborn dates corresponds with earlies termination of pregnancy in
      rescue cerclage subjects, with median gestational age at time of delivery 28
      weeks (range 19-41), after emergency operation median achieved 36 weeks (range 23
      41). The median gestational age at delivery after elective cerclage was 36 weeks
      (range 22-41). Nine fetal losses were in the rescue group, sex abortions (from
      260 to 560 grams) and three early neonatal deaths (530, 550, 1150 grams).
      CONCLUSION: These results confirm that the use of cervical cerclage in prevention
      of the premature labour is rather rare as well as achievement outcomes did not
      fulfil our expectations. This fact could have been considered in the care of
      pregnant and lead to restriction of unnecessary investigations of uterine cervix
      especially in non risk and asymptomatic population.

PMID- 18711959
TI  - [Semiquantitative analysis of mRNA aromatase expression in eutopic endometrium as
      a diagnostic marker of endometriosis and estrogen dependent diseases].
AB  - OBJECTIVE: To determine clinical benefits of mRNA aromatase expression in entopic
      endometrium as a diagnostic marker of endometriosis. DESIGN: Prospective clinical
      trial. SETTING: Department of Obstetrics and Gynaecology of Jessenius Medical
      Faculty and Faculty Hospital, Martin. METHODS: The expression of mRNA aromatase
      of eutopic endometrium was determined among women who underwent laparoscopy or
      laparotomy due to pelvic pain, infertility or benign pelvic tumor. Endometriosis
      was confirmed histologicaly and classified by rAFS. RESULTS: On the basis of
      entering criteria 23 women were enrolled in this study and divided into two
      subgroups: 12 endometriotic and 11 without endometriosis. Sensitivity of
      aromatase expression was 75% and specificity 54.5% at the cut-off value of at
      least minimal aromatase activity. By the presence of estrogen-dependent diseases-
      endometriosis, myomas or endometrial hyperplasia 18 women were compared to 5
      disease free women. In this case, sensitivity of aromatase expression was 72.2
      and specificity 80%. CONCLUSION: Aromatase expression in eutopic endometrium is a
      good diagnostic marker for endometriosis.

PMID- 18711960
TI  - [Detection of HPV DNA in lymph nodes in early stages cervical cancers].
AB  - OBJECTIVE: Review recent knowledge concerning significance of detection of DNA
      HPV in regional lymph nodes in cervical cancer patients. TYPE OF THE STUDY:
      Literature review. SETTING: Department of Obstetrics and Gyneacology, 1st Faculty
      of Medicine, Charles University and General Teaching Hospital, Prague. RESULTS:
      Metastatic involvement of pelvic lymph nodes is the most important prognostic
      parameter in early stages cervical cancer. Still, almost 20% of patients with
      negative pelvic nodes experience recurrence. Detection of HPV DNA in lymph nodes
      might be a marker of occult metastatic involvement. However, published data are
      limited, mostly due to inconsistent methodology. Only 3 prospective studies
      evaluating HPV from fresh or frozen tissue were published till now, all other
      retrospective studies extracted HPV DNA from paraffin embedded samples. A few
      papers showed correlation between HPV DNA and metastatic involvement of pelvic
      lymph nodes. DNA HPV identification in histopatology-negative nodes was
      considered as a risk factor for recurrence. Presence of DNA HPV 18 in
      histopathology-negative pelvic nodes was described as a poor prognostic factor;
      however prognostic significance of individual genotype is still unclear.
      CONCLUSION: Detection of high risk HPV DNA in regional lymph nodes is a good
      candidate for prognostic parameter in early stages cervical cancers. The group of
      women with both absence of metastatic involvement and negative HPV DNA evaluation
      of regional lymph node should represent a cohort of patients with particularly
      good prognosis.

PMID- 18711962
TI  - [The age of women treated for infertility increases].
AB  - OBJECTIVE: The age of women at first child in the Czech Republic increases. We
      investigated whether this trend translates into the group of patients treated for
      infertility by IVF. SETTING: Fertimed, infertility centre, Olomouc. METHODS: We
      summoned data from 4689 women treated for infertility in our centre. We
      investigated the age of the patient, FSH levels, E2 levels, number of FSH units
      needed for ovarian stimulation, number of oocytes and embryos. We analysed the
      results by the method of regression analysis. RESULTS: We found that the mean age
      increased from 28.7 to 32 years in a period of 10 years. We also demonstrated
      that the increasing age was accompanied by a decrease in ovarian function.
      CONCLUSION: Women older than 32 years should be informed about the decreased
      ability to conceive. The treatment of women for infertility can be complicated by
      the growing age of patients in coming decades.

PMID- 18711961
TI  - [Expression of p53, Ki-67, bcl-2, c-erb-2, estrogen, and progesterone receptors
      in endometrial cancer].
AB  - OBJECTIVE: To assess the immunohistochemical expression of p53, bcl-2, c-erb-2,
      Ki-67, estrogen and progesterone receptors in endometrial cancer patients.
      DESIGN: Experimental study. SETTING: Department of Obstetrics and Gynecology,
      Institute of Human Genetics, Department of Pathology, Palacky University Medical
      School and University Hospital, Olomouc. METHODS: We studied 103 cases of primary
      untreated endometrial carcinoma in which the p53, bcl-2, c-erb-2, Ki-67, estrogen
      and progesterone receptor antigens were investigated by an immunohistochemical
      method. We evaluated the correlations among the immunohistochemical staining
      assessed by histoscore, and the age, grading, depth of invasion, stage of the
      neoplasia and extrauterine disease. RESULTS: Mean age was 67 years (range 35-90).
      p53, bcl-2, c-erb-2, Ki-67, estrogen and progesterone receptors were positive in
      49 (48%), 81 (79%). 18 (17%), 99 (96%), 73 (70%) and 87 (84%) patients
      respectively. There was no clear association between immunohistochemical
      parameters and the age of patients. p53 and Ki-67 overexpression was found to be
      related to poor grade of differentiation, deeper myometrial invasion, advanced
      stage of neoplasia and extrauterine spread of disease. Immunostaining for bcl-2
      correlated inversely with FIGO stage, while c-erb-2 was overexpressed in tumors
      with deeper myometrial invasion. Estrogen and progesterone receptor positive
      tumors showed a statistically significant association with clinicopathological
      parameters of better clinical outcome. CONCLUSION: The overexpression of p53 and
      Ki-67 seems to indicate more malignant phenotype, while bcl-2 and c-erb-2 may
      have a limited role in the identification of high-risk tumors.

PMID- 18711963
TI  - [Tension free vaginal tape and transobturator suburethral tape for surgical
      treatment of stress urinary incontinence].
AB  - OBJECTIVE: The purpose of this study was to prospectively and randomly compare
      tension free vaginal tape (TVT) with transobturator suburethral tape (TVT O) for
      the surgical treatment of stress urinary incontinence (SUI) in women. STUDY
      DESIGN: 288 women with SUI were randomly assigned to either TVT (n-141) or TVT O
      (n-147). The preoperative evaluation included QoL questionare and a comprehensive
      urodynamic examination. The 1-year outcome included a urodynamic study. RESULTS:
      Patients characteristics, preoperative QoL were similar in the 2 groups. Mean
      operative time was significant shorter in TOT group. The rates of cure were
      similar rot the TVT and TVT O groups, respectively (obj.: 90.1% vs. 88.4%, subj.:
      84.7 vs. 80.9%). CONCLUSION: TOT appears to be equally efficient as TVT for
      surgical treatment of stress urinary incontinence in women.

PMID- 18711964
TI  - [Risk factors for postsurgical uroinfection in gynecology].
AB  - OBJECTIVE: This study eims to evaluate risk factors for postsurgical uroinfection
      (UTI) in gynecology. DESIGN: Clinical retrospective trial. SETTING: Obstetrics
      and Gynecology Department, Merciful Brothers Hospital, Brno. MATERIALS AND
      METHODS: All of 290 women who underwent hysterectomy and/or anterior vaginal
      repair (with or without anti-incontinence operation) in our hospital during the
      year 2005 were studied. The following data were noted: age, weight, anamnestic
      UTI, diabetes, other serious morbidity, moving disorders, estrogene deficiency,
      the type of surgery, the type of catheter and the duration of its indweling,
      intra/postoperative complications, urologic symptoms and urine analysis including
      bacteriology on the 6th postoperative day. There were excluded cases with
      antibiotic therapy (due to non-urological indications) from the study. The risk
      factors were assessed on the rest of 262 women, in two subgroups according to the
      catheter type (Foley/minicatheter), as there were remarcable differences in the
      indwelling time and other characteristics. "Mini-catheter" (a thin transurethral
      catheter) enables spontaneous voiding as well as measuring the postmiction
      residuum. It was used in case of anterior vaginal repair or Burch operation and
      extracted as soon as the voiding function had been restored, mostly on the 2nd
      3rd day. The Foley was used in the others, mostly for one day. The unidimensional
      (Fisher and Mann-Whitney test) and multidimensional (logit model, Walds
      statistic) analyses were performed. The influence of the type of catheter itself
      was analysed within an indwelling time period (20-32 hours) in which women of
      both subgroups were present. RESULTS: The Foley group (115 women, indwelling time
      16-32 hours) had 3.5% UTI, none of studied factors was estimated as significant.
      In the mini-catheter group (147 women, catheterisation for 20-234 hours) was
      35.4% UTI, with two risk factors: the time of catheterisation (p = 0.000029) and
      complications (p = 0.021515). The statistic model we have used (logit analysis)
      predicts UTI with sensitivity 61.5 and specificity 89.5. There was no difference
      in the risk of UTI between the two types of used catheters in case of equal time
      of their insertion. CONCLUSION: Postsurgical UTI was connected significantly with
      the duration of catheterisation and intra/postoperative complications. In case of
      short time catheterisation (up to 32 hours), however, the percentage of UTI was
      low and no risk factor was assessed as significant.

PMID- 18711965
TI  - [Appendiceal mucocele in differential diagnosis of tumors in pelvic region].
AB  - OBJECTIVE: To report two cases of appendiceal mucocele in patients with suspected
      gynecological pathology. DESIGN: Case report. SETTING: Department of Obstetrics
      and Gynecology, Medical Faculty of Charles University and Faculty Hospital Hradec
      Kralove. SUBJECT AND METHOD: We report two cases of appendiceal mucocele
      diagnosed and treated at our department. CONCLUSION: Appendiceal mucocele is a
      rare pathology, characterized by abnormal accumulation of mucous in appendix
      lumen. It is four times more common in females with a mean age of about 55 years.
      The pathogenesis could be neoplastic or non-neoplastic. Appendiceal mucocele with
      its anatomic location must be considered in terms of differential diagnosis of
      masses in pelvic region. Preoperative diagnosis is important, alerting the
      surgeon of an unintended rupture during surgery and avoiding the development of
      pseudomyxoma peritonei. US and CT were reported to be valuable.

PMID- 18711966
TI  - [Single umbilical artery syndrome (review and a case report)].
AB  - OBJECTIVE: Authors present a review of epidemiology, ethiopathogenesis and
      current diagnostic approaches of single umbilical artery syndrome (SUA). They
      describe one case of SUA complicated with intrauterine growth restriction (IUGR),
      and possible management of risk pregnancy like that. SUBJECT: Literature review
      and a case report. SETTING: Department of Gynecology and Obstetrics, Jessenius
      Medical Faculty, Commenius University, Martin, Slovak Republic. SUBJECT AND
      METHOD: The observation and management of one case with SUA and IUGR. CONCLUSION:
      SUA is the most frequent umbilical malformation. The finding of isolated SUA does
      not markedly increase perinatal morbidity and mortality, but its association with
      other pathologies leads to higher perinatal losses. An accurate management is
      still unclear (invasive antenatal diagnosis, especially), but SUA diagnosis
      should be a reason for more strict observation, timing of delivery, appropriate
      mode of delivery, and/or for more prompt intervention during pregnancy and labor.
      An early intervention and appropriate termination of pregnancy allowed delivery
      of live premature newborn with good posptartal adaptation and good prognosis was
      delivered after early intervention in our case.

PMID- 18711967
TI  - [Is fear of external cephalic version well-founded?].
AB  - BACKGROUND AND OBJECTIVE: External cephalic version (ECV) is often denied due to
      fear of complications and pain during this procedure. The aim of this study was
      to assess maternal pain perception during ECV and to report the incidence of
      complications associated with this procedure. DESIGN: Prospective study. SETTING:
      Hospital of Merciful Brothers, Brno. METHODS: Study included 110 women undergoing
      ECV. Pain was measured by visual analog scale (VAS) and descriptive part of Czech
      version of McGill Pain Questionnaire (MPQ). The overall pain rating index (PRI)
      and PRI of sensoric (S), affective (A), evaluating (E) and miscellaneuos (M)
      descriptors of pain was assesed. The assesment was performed in all patient and
      group of successful and failed ECV was compared by t-test. All complications
      during ECV were recorded. Incidence of operative deliveries after successful ECV
      was compared with control group included parturients with cephalic presentantion
      by odds ratio (OR) with 95% confidence interval (95% CI). RESULTS: Forty two ECV
      (38%) was successful. Mean value of VAS was 4.9, PRI 14.4 (SD = 1.9). PRI of
      particular qualities of pain: S = 8.0, A = 1.9, E = 2.6, M = 2.1. The significant
      diference between successful and failed ECV group was in VAS (4.2 vs 5.4, p =
      0.001), PRI -A (1.3 vs 2.2, p = 0.018) and PRI-M (1.5 vs 2.5, p = 0.015). We
      recorded 2 (1.8%) cases of transient fetal bradycardia, 8 ECV (7%) was
      discontinued for pain and in 52% women after ECV transient decrease in fetal
      heart rate variability occured. No serious complication was recorded. The
      incidence of caesarean section after successful ECV was 21% and in control group
      16% (OR 1.4 95%.CI 0.62; 3.01). Incidence of instrumental delivery after ECV was
      12%, in control group 5% (OR 2.7 95% CI 0.93; 7.27). CONCLUSION: The pain during
      ECV was mild and well tolareted. The incidence of complications was small and the
      most of them were not serious. In this study no reasons for denying ECV were
      found.

PMID- 18711969
TI  - [Legal medicine of yesterday, today and tomorrow...].

PMID- 18711968
TI  - [Failed home breech vaginal delivery of hydrocephalic fetus and it's
      consequences].
AB  - Case from Sri Lanka describes a chain of catastrophic complications in a patient
      whose main problem--a hydrocephalic fetus with macrocephaly in breech
      presentation, was not diagnosed during antenatal care. The delivery was taking
      place at home up to shoulders and arms, the head was not delivered. The patient
      with threatening uterine rupture was transferred to District Hospital and seen by
      doctor 10 hours later. Destructive operation of hydrocephalic head was performed,
      the procedure was accompanied by rupture of uterus and followed by cardiac
      arrest. The patient was resuscitated and hysterectomy with bilateral
      salpingoophorectomy was performed, the procedure was complicated by disseminated
      intravascular coagulopathy. The patient survived, 5th postoperative day was
      treated for malaria and was discharged eight days after operation.

PMID- 18711970
TI  - [Molecular autopsy of sudden cardiac death: from postmortem to clinical
      approach].
AB  - Sudden cardiac death is one of the most prevalent cause of death in developed
      countries. Its aetiology varies according to the age. Some cardiac diseases may
      explain sudden death with minimal or no anatomic findings. However, many cardiac
      diseases, as for example channelopathies and hypertrophic cardiomyopathy have a
      genetic basis. Therefore genetic analyses (molecular autopsy) are becoming a
      useful tool in forensic medicine to identify the cause of sudden cardiac death
      and to improve the early diagnosis of asymptomatic carriers among relatives.

PMID- 18711971
TI  - [Fitness to drive: which assessment by doctors in 2008?].
AB  - Medical problems related to car driving are more and more complex and frequent.
      In the most areas of Switzerland each doctor can be asked to assess the fitness
      to drive of his patients. Several guidelines from medical societies have been
      published recently in Switzerland. Therefore it appears to be useful to
      synthesize the essential knowledge to have before signing fitness-to-drive
      certificates.

PMID- 18711972
TI  - [New challenges in forensic psychiatry].
AB  - The new Swiss criminal code and the recent evolution of evaluation methods have
      led to change in the three main areas of forensic psychiatry: criminal
      responsibility, credibility of child sexual abuse allegations, and dangerousness.
      The assessment of criminal responsibility requires the retrospective examination
      of the cognitive and volitive capacities of the accused. If needed, mandatory
      therapeutic propositions that conform to the new criminal code must be
      recommended. With regard to child sexual abuse allegations, the credibility of
      the allegations is analysed with specific scales, such as Statement Validity
      Analysis, interpreted in light of the current state of knowledge in child
      development and child psychiatry.

PMID- 18711973
TI  - [Forensic toxicology, a growing scientific discipline].
AB  - Forensic toxicology has to bring evidence of substances that could have been
      involved directly or indirectly in the cause of death or that could influence the
      behaviour of somebody. The increase of the consumption of illegal and legal drugs
      in modern societies during last decades gave a boost to forensic toxicology.
      Moreover, improvement with analytical technology gave tools with high degrees of
      sensitivity and specificity for the screening and quantification of a large
      amount of substances in various biological specimens, even with very low
      concentration resulting of a single dose of medication.

PMID- 18711974
TI  - [Forensic imaging].
AB  - In recent years, modern techniques of medical imaging such as MDCT (multidetector
      computed tomography) and MRI (magnetic resonance imaging) have pioneered post
      mortem (pm) investigations, especially in forensic medicine. Particularly pm
      angiography permits investigating the vascular system in a way which is not
      possible by performing only conventional autopsy. Beside these radiological
      methods, other modem visualizing techniques like the three dimensional (3D)
      surface scan have been implemented in order perform reconstructions of complex
      cases. By the use of pm imaging techniques, more objective and accurate
      documentations can be realized that permit an increase of quality in forensic
      investigations.

PMID- 18711976
TI  - [Urbanisation, health and travel].
AB  - 2007 can be considered as a milestone in human history: over 50% of the world
      population lives in cities. In 2030, 60% of the population will live in cities.
      Currently the urbanization process prevails in developing countries, particularly
      in Asia and Africa. Cities in developing countries are characterised by an
      important heterogeneity, where the poorest areas are next to the richest.
      Urbanization has an important impact on health and diseases profile. An
      increasing number of travellers visit cities in tropical areas. Risk factors such
      as air pollution, heat, security, accidents or infectious diseases prevalent in
      urban environment should be taken into consideration when advising travellers.

PMID- 18711975
TI  - [Genetic identification of dead persons: which reference sample should be used?].
AB  - Identification of a deceased person consists in connecting this person with
      reference data. Within this context, DNA analyses allow to use samples coming
      from the deceased himself (personal reference) or from persons closely related to
      the deceased (familial reference). The analysis of 132 genetic identifications
      performed between 2003 and 2007 in Switzerland illustrates that familial
      references are predominantly used. Recommendations are presented to optimize the
      genetic identification process. In particular, personal references collected on
      the deceased when alive should be preferred. When this is not possible, several
      reference samples should be analysed in order to minimize the probability of a
      fortuitous connection.

PMID- 18711977
TI  - [Gastronomic genes].

PMID- 18711978
TI  - [Two a priori encouraging results in oncology].

PMID- 18711979
TI  - [Rise of "doulas" in obstetrics].

PMID- 18711980
TI  - [Smoke screens and stigmatization of smokers].

PMID- 18711981
TI  - [Google.org: the octopus, the philanthropist and health].

PMID- 18711982
TI  - [Is it necessary to learn to forget?].

PMID- 18711983
TI  - Ethiopian Medical Association "Optimism in the new millennium".

PMID- 18711984
TI  - Blood safety & prevalence of transfussion transmissible viral infections among
      donors at the Red Cross Blood Bank in Gondar University Hospital.
AB  - BACKGROUND: Although millions of lives are saved by blood transfusion, unsafe
      transfusion is also putting millions of people at risk of Transfusion
      Transmissible Infections (TTI). In Ethiopia the safety and magnitude of blood
      transfusion and TTIs is not well investigated OBJECTIVE: to investigate the
      magnitude of TTIs and assess TTI related risk factors among blood donors.
      METHODS: Cross-sectional study among blood donors at the Red Cross Society Blood
      Bank in Gondar University Hospital, North West Ethiopia. RESULTS: The study was
      conducted among 600 adult blood donors between April and July 2004. Their mean
      age was 28 +/- 10.4 years (range: 16-64) and 66% of them were urban dwellers. The
      donors included farmers (30.7%), daily laborers (22.7%) and students (20%). All
      the donors were first time donors and 75% of the donations were replacement
      donations by remunerated donors or family members. The prevalence of HIV,
      Hepatitis B surface antigen (HBSAg) and Hepatitis C virus (HCV) infections were
      4.5% (95%CI: 3.0-6.6), 8.2% (95%CI: 6.2-10.7) and 5.8% (95%CI: 4.2-8.1),
      respectively. The overall discard rate of donated blood because of these viral
      markers was 16.3%. In univariate analysis, HCV infection was significantly
      associated with presence of HIV (OR: 5.36, 95%CI: 2-14.3). Experiences of
      traditional surgical incisions or phlebotomy were present in 93.8% of donors.
      While 6.5% of donors admitted a history of multiple sexual partners, none of them
      admitted a history of any sexually transmitted infections (STI). CONCLUSION: The
      prevalence of TTIs among blood donors is very high. The majorities of blood
      donors are replacement or paid donors with one or more of the risk factors for
      TTIs implying that blood transfusion is unsafe. These findings call for the
      urgent implementation of the national strategy for safe blood transfusion in
      Ethiopia. As the utilization of advanced technology and skilled-personnel-based
      screening of blood are not in the immediate horizon, establishing stringent
      selection criteria of donors and setting clinical indications for transfusion
      would be indispensable and cost-effective interventions to minimize the risk of
      TTIs to blood recipients in Ethiopia.

PMID- 18711985
TI  - Seroprevalence, pattern and outcome of HIV/AIDS among surgical patients at Gondar
      University Hospital.
AB  - BACKGROUND: HIV/AIDS affects not only medical but also surgical patients. Post
      operative outcome could be influenced in a form of increased morbidity or
      mortality. OBJECTIVE: To determine prevalence, pattern and out come of HIV/AIDS
      among surgical patients at Gondar University Hospital (GUH). PATIENTS AND METHOD:
      All patients admitted to the department of surgery of GUH from October 2001 to
      February 2002 were included The ELISA was used to test for HIV Patients were
      categorized in to four groups according to their cause of illnesses; namely
      General surgical, Trauma, Infective and neoplasia. RESULTS: Seventy-three (12.1%)
      of the 604 patients tested were positive for HIV. Those patients who had some
      sort of infectious surgical illnesses including appendicitis and cholecystitis
      had the highest prevalence (25.7%). It was observed during the study that
      morbidity and mortality were higher among the patients who were considered to
      have developed AIDS. CONCLUSION: The study has established an HIV/AIDS prevalence
      rate of 12.1% among surgical patients at Gondar University Hospital. Patients
      with infectious surgical processes were affected most. It is recommended that
      this group of patients need voluntary counselling and testing (VCT) for HIV and
      may benefit from its outcome by getting anti-retroviral therapy.

PMID- 18711986
TI  - Sexual coercion and reproductive health outcomes among young females of Nekemte
      Town, South West Ethiopia.
AB  - OBJECTIVES: This study was conducted to assess adverse outcomes and associated
      factors of sexual coercion among young females in Nekemte Town. METHODS: A cross
      sectional community based study was conducted using both qualitative and
      quantitative data collection methods. A sample of 641 young females aged 10-24
      years was taken from 3 sub-cities by systematic sampling procedure. Quantitative
      data were collected using a pre-tested structured questionnaire. Six focus group
      discussions targeting different groups were held to capture qualitative data.
      RESULTS: Overall prevalence of sexual coercion was 101(15.8%). Compared to young
      females who did not report lifetime sexual coercion, victims of sexual coercion
      had significantly increased likelihood having more than one sexual partner during
      the last six months OR (95%CI): 3.4 (1.3, 8.7), unintended pregnancy OR (95%CI):
      3.57 (1.5, 8.3) and more than one symptom of reproductive tract infections OR
      (95%CI): 2.4 (1.3, 8.7). In addition, victims of sexual coercion had
      significantly lower likelihood of using modern contraception OR (95%CI): 0.51
      (0.2, 1.0), increased likelihood of reporting unintended pregnancy OR (95%CI):
      3.4 (1.3, 8.9). CONCLUSION: Sexual coercion is a public health problem among
      young females in the study community due to its consequences on the physical,
      psychological and social well being. It is recommended that emerging program
      interventions on Reproductive Health, sexuality, and HIV/AIDS by various
      stakeholders need to take this problem into consideration in order to address the
      full context of young females' lives. Interventions targeting the social and
      behavioral factors leading to these problems need to be instituted to curb the
      problem.

PMID- 18711987
TI  - Experience of uetropubic urethrolysis and sling operation for the treatment of
      post fistula repair residual incontinence at the Addis Ababa Fistula Hospital,
      Addis Ababa Ethiopia.
AB  - BACKGROUND: Incontinence after successful closure of fistula is a very
      challenging problem. Neither the cause nor the optimal treatment is well
      established Biological slings are still the option of treatment in the developing
      world whereas in the developed world they are substituted by synthetic meshes.
      OBJECTIVE: The study aims to asses outcomes of retro pubic urethrolysis and sling
      operation in the treatment of post fistula repair incontinence. METHODOLOGY: This
      study is a cross-sectional descriptive study done in Addis Ababa Fistula
      Hospital. A total of 56 patients who under went retro pubic urethrolysis and
      sling operation were analyzed. RESULTS: The study showed that the over all
      success rate of the operation is 73.2%. However complete cure was achieved in
      only 41.1% of the cases. Bothersome urinary retention was seen in 8.9% of cases.
      In more than one third of the cases there were post operative complications.
      CONCLUSION: Biological sling is effective in the treatment of post fistula repair
      incontinence. It has comparable results to that of synthetic slings when used in
      patients with fixed urethra and intrinsic urethral sphincter deficiency. However
      it is imperative to see the long term results. Moreover, Urodynamic examination
      for patient selection and measures to reduce infection are recommended.

PMID- 18711988
TI  - Clinical estimation of fetal weight in low resource settings: comparison of
      Johnson's formula and the palpation method.
AB  - BACKGROUND: Estimation of fetal weight is important for antenatal and intrapartum
      clinical decision-making. Sonographic estimates may not always be available in
      low resource settings. In such instances it is essential to study the reliability
      of clinical estimation of fetal weight in assisting decision-making. OBJECTIVES:
      Estimate the accuracy of the Johnson's formula and the palpation methods of fetal
      weight estimation and their correlation. SETTINGS: Maternity units of three
      teaching hospitals (Tikur Anbessa, Gandhi Memorial and Saint Paul's) in Addis
      Ababa, Ethiopia. SUBJECTS AND METHODS: Three hundred and twenty mothers were
      included in the study at the three hospitals from May 1 to September 30, 2004.
      Fetal weight was estimated for each mother using both methods prior to delivery.
      Accuracy of estimation was determined by the percentage error, absolute
      percentage error and the proportion of estimates within 10% of the actual birth
      weight. Statistical analysis was performed using the student's t test, paired t
      test, comparison of correlated variances using the modified F test, Wilcoxon sign
      test and the X2 test. RESULTS: Actual birth weight was 3152 +/- 494 grams;
      ranging from 1600-5250. The mean of all error terms of EFW (estimated fetal
      weight) with palpation method were significantly smaller than those of Johnson's
      method and rate of estimates within 10% of actual birth weight was significantly
      higher for the palpation method (65%, versus 38%). For birth weights less than
      2500 grams both methods overestimated the birth weight; the mean error of the
      palpation method was significantly smaller than those of the Johnson's method. In
      the 2500-3999 birth weight range, only the palpation method had no systematic
      error, whereas the Johnson's method systematically overestimated the birth
      weight. The mean errors of the palpation method were significantly smaller and a
      rate of birth weight +/- 10% significantly higher than those of the Johnson's
      method (68% versus 40%). In the larger weight (>4000 gms), the Johnson's method
      had less systematic error compared to the palpation method (mean percent error = 
      0.9 + 11.3. p =0.42), although the small sample size in this group precludes a
      firm conclusion of the issue in this category. CONCLUSIONS: Estimation of fetal
      weight by the Palpation method appears to be more accurate than the Johnson's
      method. In the lower and average birth weight range the palpation method is the
      more accurate of the two, while in the higher weight category the Johnson's
      method appears to be more accurate.

PMID- 18711989
TI  - The size of anterior fontanel in neonates and infants in Addis Ababa.
AB  - INTRODUCTION: Assessment of the size of the anterior fontanel is a part of the
      routine examination in neonatology and pediatrics. Knowledge of the normal
      variations in AF size may be helpful in the early recognition of disorders. The
      mean size of the AF in neonates and infants in Addis Ababa is not known and the
      current looks in to this issue. METHODS: A cross sectional study was carried out
      on 687 apparently healthy neonates and infants who were seen consecutively from
      January 2003 to December 2003. RESULTS: There were 363 males and 324 females at
      the ages of 3, 46, 76, 106 and 270 days. The mean of anterior-posterior and
      lateral dimensions was considered to be the size of anterior fontanel. The mean
      AF size at the age of 3 days was 3.35 +/- 0.94 cm and showed a decline in the
      respective postnatal ages. 0.8% of infants at the age of 76 days had closed AF
      and the percentage of closure rose to 2.3 and 39.6 at the ages of 106 and 270
      days respectively. CONCLUSION: This study supported previous reports indicating
      racial difference in the size and time of closure of AF. The size and time of
      closure of AF are used to monitor the development of brain and general state of
      health of the individual. Further study is recommended indifferent parts of
      Ethiopia to establish age-related standard of AF size.

PMID- 18711990
TI  - Catheterized and non-catheterized urinary tract infections among patients
      attended at Jimma University Teaching Hospital, Southwest, Ethiopia.
AB  - OBJECTIVES: Prospective cross sectional study was undertaken to assess the
      bacterial profile and antimicrobial resistance pattern of catheterized urinary
      tract infection in comparison with non-catheterized UTI in Jimma University
      Teaching Hospital, Southwest, Ethiopia. METHODS: One hundred and twenty patients,
      30 catheterized (age range 20-78 years, male to female ratio 0.36:1) and 90 non
      catheterized patients (age range 7-60 years, male to female ratio 2:1) with
      symptoms and signs of UTI were investigated for significant bacteriuria from
      January to March 2005. RESULTS: Significant bacteruria was observed in 13/30
      (43.3%) and 20/90 (22.2%) of catheterized and non-catheterized patients,
      respectively (p<0.05). Klebsiella spp. (33.3%) and E. coli (27.7%) were the most
      common bacteria pathogens isolated in both groups and followed by Enterobacter
      spp. (6%). Proteus spp., Pseudomonas spp. and coagulase negative Staphylococci
      were isolated only from catheterized patients. Gram-negative bacteria isolated in
      both groups showed a high level of resistance (88-100%) to ampicillin,
      amoxicillin carbencillin and cephalexin. and intermediate level of resistance (48
      68%) to amoxicillin-clauvlanic acid, gentamicin and trimethoprim
      sulphamethoxazole. Low level of resistance (16-24%) observed to amikacin,
      ciprofloxacin, nalidxic acid and nitrofurantoin. Similar pattern of resistance
      was observed in all the gram-positive isolates including for methicillin,
      oxacillin and vancomycin (100%). On the other hand, amoxicillin-clavulanic acid
      and polymixin B were found effective against all gram-positive bacteria isolated
      from both groups. CONCLUSION: The present study revealed that UTIs in both
      catheterized and non-catheterized patients was shown very high resistance pattern
      to most of antibiotics in use mainly at Jimma University Teaching Hospital,
      southwest Ethiopia. This calls for concerted efforts at all levels including
      regulatory bodies and the public healthcare providers as well as private ones.
      Creating awareness of the community will also have a significant role to curb
      this problem.

PMID- 18711991
TI  - Invitro antibacterial activity of crude preparation of myrtle (Myrtus communis)
      on common human pathogens.
AB  - BACKGROUND: Myrtle "Addus" (Myrtus communis) has long history as a traditional
      medicine/or different infectious disease by many peoples of the world and in
      Ethiopia too. OBJECTIVE: To asses the antibacterial activity of crude myrtle on
      some common human pathogens. METHODS: This experimental study was conducted in
      Jimma University from February to April 2004. The antimicrobial activity/ minimum
      inhibitory and minimum bactericidal concentrations/ of the crude preparation of
      Myrtle on E. coli, S. aureus, P. aeruginosa, P. vulgaris, P. mirabilis, K.
      aerogenes, S. typhi & S. shigie was determined using agar dilution methods.
      RESULTS: The Minimum Bactericidal Concentration of Myrtle for most tested
      microorganisms was similar to the Minimum Inhibitory Concentration. i.e. 0.5
      mg/ml. for S. aureus, 2.5 mg/ml for P. mirabilis and P. vulgaris, 15 mg/ ml for
      Klebssiela and S. typhi, 20 mg/ml for P. aeruginosa. And the MBC of Myrtle for
      the two relatively least sensitive species, Shigella and E. coli was 40 mg/ml and
      45 mg/ml of media, respectively. The antibacterial activity of Myrtle was
      markedly increased by 18 times after it has been autoclaved at 121 degrees C for
      15 minutes. CONCLUSION: The preliminary study supports its traditional claim of
      effective anti-infective and could initiate further study that may ultimately
      facilitate to use myrtle as an antimicrobial agent. However, pharmacologically
      standardization and clinical evaluation on the effect of myrtle is essential,
      before using it as antibacterial agent in vivo.

PMID- 18711992
TI  - The invitro assessment of antibacterial effect of papaya seed extract against
      bacterial pathogens isolated from urine, wound and stool.
AB  - BACKGROUND: Carica papaya family Caricaceacae is one of the herbal remedies,
      which has recently become a subject of research focus. It is used in traditional
      medicine for variety of purposes in treating infectious and noninfectious
      diseases. OBJECTIVE: The objective of this study was to assess the antibacterial
      effect of papaya seed extract against bacterial pathogens isolated from wound,
      urine and stool. METHODS: This analytical experimental study was conducted in
      Jimma University, School of Medical Laboratory Technology, Microbiology
      laboratory between February to March 2005. The antibacterial activity of methanol
      extract of papaya seed was investigated against specific pathogenic bacteria
      isolated from wound, urine and stool by an agar dilution technique and the crude
      preparation was assessed by an agar diffusion technique. The growth or inhibition
      of control strains of Escherichia coli, Staphylococcus aureus, Salmonella typhi,
      and Pseudomonas aeruginosa as well as the clinical isolates of these bacteria
      were determined in growth media. RESULTS: Results obtained in this study indicate
      that the minimum inhibitory concentration of papaya seed extract for 50% of the
      test bacteria was 18.38mg/ml and for S. typhi the MIC was at 11.8 mg/ml of
      extract. However, the growth inhibitory effect of papaya seed extract was not
      observed for P. aeruginosa up to 26.25 mg /ml of extract. Even though, the
      minimum bactericidal concentration is higher than the minimum inhibitory
      concentration of papaya seed extract (13.13 mg/ml, 11.8 mg/ml respectively)
      against S. typhi control and clinical isolates, the minimum bactericidal
      concentration for 50% of the tested bacteria was found to be similar with the
      minimum inhibitory concentration of the test bacteria, CONCLUSION: Papaya seed
      could be used as an effective antibacterial agent for the tested organisms.
      Nevertheless, preclinical studies including invivo animal models and clinical
      trial on the effect of the seed are essential before advocating large-scale
      therapy.

PMID- 18711993
TI  - Genetic characterization and progression of B3 measles genotype in Ethiopia: a
      study of five measles outbreak cases.
AB  - BACKGROUND: One of the countries where measles remains endemic is Ethiopia.
      Previously, sequence data from Measles Viruses (MV) circulating in Ethiopia were
      obtained from clinical specimens. Now the Ethiopian Health and Nutrition Research
      Institute (ENHRI) has implemented cell culture techniques to isolate measles
      virus and molecular epidemiologic studies can be generated more easily.
      OBJECTIVE: To characterize the strains of Measles Virus circulating in Ethiopia
      during measles outbreaks in 2006 using viral isolates, and compare the results to
      previously identified Ethiopian strains. METHODS: A case study and convenience
      sampling method were conducted on five measles outbreak cases tb identify the
      circulating measles virus genotype in Addis Ababa and Amhara regions of Ethiopia
      in 2006. RESULTS: Three isolates were obtained from five specimens collected in
      two regions (1 from Amhara: Bahir Dar, and 2 from Addis Ababa: Addis Ketema and
      Kolefe Keranio subcities) in Ethiopia during 2006. The viral isolates were
      analyzed using standard genotyping protocols and were classified as genotype B3,
      identical to the strain circulating widely in West Africa and imported into
      Europe (Britain, Netherlands, Germany) and America (Mexico, USA, Canada).
      CONCLUSION: The conserved sequences among three isolates, covering a 3-month
      period, suggest that this B3 strain was circulating in Addis Ababa, Bahir Dar and
      possibly elsewhere in Ethiopia. To interrupt the transmission and circulation of
      MV, Ethiopia needs a strong national program of epidemiological surveillance,
      with characterization of circulating MV performed in a timely manner.

PMID- 18711994
TI  - Traditional treatment of mental disorders in rural Ethiopia.
AB  - BACKGROUND: Mental disorders are known to be as prevalent in Ethiopia as in other
      countries. Only 26 psychiatrists are working in the country with close to 80
      million inhabitants. To this should be added clinics run by psychiatric nurses in
      most of the general hospitals. This means that still most of the mentally ill in
      the country are trected and cared for in a traditional way. OBJECTIVES: This
      paper presents the situation regarding traditional treatment of mental illness in
      a rural area in central Ethiopia, Butajira, with a population of about 350,000
      persons, predominantly Muslim. METHODS: All traditional healers in Butajira area
      were mapped by asking key informants. Twenty-four healers were so identified and
      interviewed about their perception of mental illness and the treatment they
      offer. Clients from the healers and patients from the local health centre were
      interviewed about their opinions on the service given. FINDINGS: A majority of
      both clients and patients were satisfied with the consultation, but the clients
      of the healers were more satisfied than the patients in health centres.
      CONCLUSION: As most persons with mental disorders are treated by traditional
      healers in rural Ethiopia and in most other developing countries it is important
      to do more comprehensive studies on the traditional treatment and to find ways of
      collaboration between traditional practice and modern medicine.

PMID- 18711995
TI  - Superior mesenteric artery syndrome: a rare cause of duodenal obstruction. Cases
      reports and review of literature.
AB  - The Superior Mesenteric Artery Syndrome is a rare cause of duodenal obstruction.
      We present two young Ethiopian female patients who were diagnosed with this rare
      condition. After a duodeno-jejunostomy, the patients showed significant
      improvement and were discharged in a very good condition. This is the first
      report of this rare case from Ethiopia and a brief literature review is also
      presented.

PMID- 18711996
TI  - Advanced abdominal pregnancy.
AB  - Abdominal pregnancy is one form of extra uterine pregnancy. As maternal and/or
      fetal complications often occur early in pregnancy, advanced abdominal pregnancy
      with live fetus is a rare occurrence in clinical practice. In this case report we
      have presented a 28 years old primigravida who carried live abdominal pregnancy
      until term. The report describes this rare event emphasizing on current
      diagnostic and management options and challenges.

PMID- 18711997
TI  - Hepatic veno-occlusive disease.

PMID- 18711998
TI  - Vaccine preventable diseases and vaccination coverage in Aboriginal and Torres
      Strait Islander people, Australia 2003 to 2006.
AB  - This, the second report on vaccine preventable diseases and vaccination coverage
      in Aboriginal and Torres Strait Islander people, brings together the relevant
      sources of routinely collected data on vaccine preventable diseases-
      notifications, hospitalisations, deaths, and childhood and adult vaccination
      coverage. As a result of continued improvements in the collection of data on
      Indigenous status, this second report is considerably more comprehensive, with
      data available from more jurisdictions, and more detailed presentation, including
      time trends and vaccination coverage by jurisdiction. Vaccination coverage data
      provide evidence of successful program delivery and highlight some areas for
      improvement. For universally funded vaccines in children, coverage is similar in
      Indigenous and non-Indigenous children by 24 months of age. However, delayed
      vaccination is more common in Indigenous children, with 6%-8% fewer children
      fully vaccinated at 12 months of age. More timely vaccination, particularly
      within the first six months of life, is particularly important in reducing the
      disproportionate burdens of disease due to pertussis and Haemophilus influenzae
      type b (Hib). For vaccination programs targeted specifically at Aboriginal and
      Torres Strait Islander children and adults, coverage is substantially lower than
      for those programs targeted at all Australians. This is true for hepatitis A and
      polysaccharide pneumococcal vaccine for children, and influenza and
      polysaccharide pneumococcal vaccine for adults. Targeted vaccination programs
      present a particular challenge for health services in urban areas. Nevertheless,
      the impact of vaccination programs in preventing disease and reducing the
      disparity of disease burden between Aboriginal and Torres Strait Islander and non
      Indigenous people has been substantial. This is evident in data on notifications,
      hospitalisations and deaths. Diseases which, in the past, have had devastating
      and often disproportionately high impact on Indigenous people, such as
      diphtheria, measles, poliomyelitis, smallpox and tetanus, are now completely or
      almost completely absent from Australia. Hepatitis B infection, another disease
      responsible for high levels of infection and substantial serious illness and
      death in the pre-vaccine era, is also now well controlled in age groups eligible
      for vaccination. Although invasive Hib disease is now rare in Australia since the
      introduction of vaccination in 1993, higher rates of disease persist in
      Aboriginal and Torres Strait Islander children. More research is needed into the
      contribution of environmental factors, delayed vaccination and vaccine failure to
      this continued disparity. Hepatitis A has disproportionately affected Aboriginal
      and Torres Strait Islander children in the past. Vaccination programs in north
      Queensland and in various other countries have been very successful in reducing
      the burden of hepatitis A. It is too early to assess the impact of the
      vaccination program for Aboriginal and Torres Strait Islander children that
      commenced in regions outside north Queensland in November 2005. For some other
      diseases the situation is more complicated. The substantial impact of the
      national meningococcal C vaccination program since 2003 is evident in this
      report, although the higher proportion of non-vaccine preventable serotype B
      disease in Aboriginal and Torres Strait Islander people underlines the need for a
      new vaccine to cover this serotype. Pneumonia remains the most important
      communicable disease contributor to premature mortality in Aboriginal and Torres
      Strait Islander people of all ages. In young Indigenous adults, the eightfold
      higher rate of hospitalisation compared with their non-Indigenous peers, and the
      11-fold higher rate of invasive pneumococcal disease, suggest the need for more
      widespread use of influenza and pneumococcal vaccines in this age group. Current
      coverage for Indigenous 15-49 year olds, where influenza and pneumococcal
      vaccines are funded only for those with risk factors, is low even though some 70%
      of this age group have one or more risk factors. Overall, the data presented in
      this report provide powerful evidence for the impact of vaccines in reducing
      disease in Aboriginal and Torres Strait Islander people, and also point to areas
      for further improvement. Immunisation programs are an example of how preventive
      health programs in general can be enhanced to close the gap in morbidity and
      mortality between Indigenous and non-Indigenous Australians.

PMID- 18711999
TI  - Welcome from the new editor-in-chief.

PMID- 18712000
TI  - Establishing validity of a modified Melbourne Assessment for children ages 2 to 4
      years.
AB  - BACKGROUND: The Melbourne Assessment of Unilateral Upper Limb Function is a valid
      tool for measuring quality of upper-limb movement in children ages 5 to 15 with
      cerebral palsy. This study presents the first phase in establishing the validity
      of a modified version of the assessment for children ages 2 to 4. OBJECTIVE: We
      sought to determine whether children without neurological impairment scored
      within the top 5% on the modified assessment, to investigate compliance with test
      demands, and to investigate the relationship between the modified tool and the
      Quality of Upper Extremity Skills Test. METHOD: The test was modified and
      administered to 32 children without neurological impairment ages 2 to 4. RESULTS:
      All children ages 2.5 to 4 scored as expected and were compliant with test
      demands. CONCLUSION: The Modified Melbourne Assessment may be used with children
      ages 2.5 to 4 without neurological impairment. Investigation with children with
      neurological impairment is now indicated.

PMID- 18712001
TI  - Reliability and validity of the Test of In-Hand Manipulation in children ages 5
      to 6 years.
AB  - The Test of In-Hand Manipulation (TIHM; Case-Smith, 2000) is a five-task test
      that uses a 9-hole pegboard to examine 2 key components of in-hand manipulation:
      rotation and translation with stabilization. The authors used Rasch modeling to
      examine the TIHM's construct validity, interrater reliability, and test-retest
      reliability in 45 typically developing children ages 5.5 years to 6.5 years. A
      version of the test, revised using Rasch modeling, was found to have evidence for
      adequate construct validity and excellent interrater reliability. However, test
      retest reliability over a 2-week retest period was not supported. The TIHM
      demonstrates potential as a clinically useful assessment of in-hand manipulation.
      The test does not examine all aspects of in-hand manipulation, however, and it
      may have limited sensitivity to the performance of finger-to-palm and palm-to
      finger translation. Further validation of the test is needed before the TIHM can
      confidently be used in occupational therapy practice.

PMID- 18712002
TI  - Pilot study of the Sensory Over-Responsivity Scales: assessment and inventory.
AB  - This article describes 3 stages of construction of the Sensory Over-Responsivity
      (SensOR) Scales: instrument development, reliability and validity analyses, and
      cross-validation on a new sample. The SensOR Scales include the SensOR
      Assessment, an examiner-administered performance evaluation, and the SensOR
      Inventory, a caregiver self-rating scale. Both scales measure sensory
      overresponsivity in 7 sensory domains. Data were collected from 2 samples
      consisting of participants who were typically developing (ns = 60 and 44,
      respectively) and participants with sensory overresponsivity (ns = 65 and 48,
      respectively), ages 3 to 55. In developing the research edition, items on the
      pilot version were reviewed for their internal consistency reliability,
      discriminant validity, and construct validity. Data from both samples on the
      research edition revealed high internal consistency reliability for domains and
      the total test and significant discrimination between the overresponsive and the
      typically responsive groups (p < .05). The preliminary psychometric integrity of
      the scales, along with continued research efforts, is an important contribution
      to evidence-based practice.

PMID- 18712003
TI  - Children's perceptions of play experiences and play preferences: a qualitative
      study.
AB  - This qualitative study investigated the perceptions of play experiences and
      rationales for play choices of 6 boys and 4 girls between the ages of 7 and 11
      years. Individual in-depth interviews were completed and then transcribed, and
      the transcripts were coded and analyzed using grounded theory methodology. Fun
      emerged from the data as the core category explaining the choice of specific play
      activities for children, and 4 additional categories of characteristics surfaced
      as contributors to the children's perception of fun: relational, activity, child,
      and contextual. The relationships among the core category, the 4 characteristics
      categories, and the development of play preference and meaningfulness are
      illustrated in the Dynamic Model for Play Choice. Included is a discussion of the
      usefulness of the model in supporting the careful consideration of factors that
      will increase the perception of fun during therapeutic activities and facilitate
      client-centered pediatric practice.

PMID- 18712004
TI  - Evidence-based review of interventions for autism used in or of relevance to
      occupational therapy.
AB  - Occupational therapy practitioners are among the professionals who provide
      services to children and adults with autism spectrum disorder (ASD), embracing
      both leadership and supportive roles in service delivery. The study's primary
      aims were as follows: (1) to identify, evaluate, and synthesize the research
      literature on interventions for ASD of relevance to occupational therapy and (2)
      to interpret and apply the research literature to occupational therapy. A total
      of 49 articles met the authors' criteria and were included in the review. Six
      categories of research topics were identified, the first 3 of which are most
      closely related to occupational therapy: (1) sensory integration and sensory
      based interventions; (2) relationship-based, interactive interventions; (3)
      developmental skill-based programs; (4) social cognitive skill training; (5)
      parent-directed or parent-mediated approaches; and (6) intensive behavioral
      intervention. Under each category, themes supported by research evidence and
      applicable to occupational therapy were defined. The findings have implications
      for intervention methods, communication regarding efficacious practices to
      professionals and consumers, and future occupational therapy research.

PMID- 18712005
TI  - Modified constraint-induced movement therapy for a 12-month-old child with
      hemiplegia: a case report.
AB  - OBJECTIVE: This case report describes the use of modified constraint-induced
      movement therapy (CIMT) to improve upper-limb function in a 12-month-old child
      with right hemiplegia. It also describes parent concerns about CIMT and documents
      the short- and long-term effects of modified CIMT. METHOD: The participant was
      assessed 5 times over a 7.5-month period using the Peabody Developmental Motor
      Scales-2, Pediatric Motor Activity Log, Toddler Amount of Use Test, and Knox
      Parent Questionnaire. CIMT included a nonremovable cast worn on the unaffected
      arm and approximately 8 hr per week of occupational and physical therapy for 2
      weeks. RESULTS: Benefits of improved upper-limb function measured immediately
      after CIMT were sustained at 6 months' follow-up. No adverse events related to
      cast use were reported. DISCUSSION: The findings from this case report suggest
      that CIMT was a safe intervention associated with improving upper-limb function
      for this young child with hemiplegia.

PMID- 18712006
TI  - Effect of wearing a static wrist orthosis on shoulder movement during feeding.
AB  - OBJECTIVE: This study compares the effect of wrist immobilization with non
      immobilization on shoulder abduction, shoulder flexion, and shoulder rotation
      during feeding. METHOD: Twenty right-hand-dominant participants with no upper
      extremity dysfunction performed a controlled feeding activity under 2 separate
      wrist conditions: (1) while wearing a static wrist orthosis and (2) with the
      wrist not immobilized (free wrist). A Motion Monitor system using small magnetic
      sensors was used to measure range of motion. Data analysis included paired ttests
      to compare the 2 conditions. RESULTS: Statistically significant results were
      found for shoulder flexion and shoulder abduction, indicating increased movement
      at the shoulder while feeding when the wrist was immobilized. No significant
      difference was found in shoulder internal rotation. CONCLUSIONS: Wearing a wrist
      orthosis while feeding may alter normal movement patterns at the shoulder. Future
      research should examine the effects of wrist splinting on shoulder movement.

PMID- 18712007
TI  - Reliability, validity, and clinical utility of the Executive Function Performance
      Test: a measure of executive function in a sample of people with stroke.
AB  - This study examined the reliability and validity of the Executive Function
      Performance Test (EFPT). The EFPT assesses executive function deficits in the
      performance of real-world tasks. It uses a structured cueing and scoring system
      to assess higher-level cognitive functions, specifically initiation,
      organization, sequencing safety and judgment, and task completion. Seventy-three
      participants with mild to moderate stroke and 22 age- and education-matched
      controls completed the 4 EFPT tasks (cooking, using the telephone, managing
      medications, and paying bills). Significant differences were found between
      participants with mild and moderate stroke and healthy control participants. The
      EFPT can help occupational therapists determine the level of support needed by
      people with cognitive impairments to perform complex instrumental tasks.
      Objective information derived from this assessment is an essential part of the
      process of determining whether the person can live independently and helping
      families understand how to support the performance of their family members at
      home.

PMID- 18712008
TI  - Effects of task instructions and target location on reaching kinematics in people
      with and without cerebrovascular accident: a study of the less-affected limb.
AB  - OBJECTIVE: We investigated how verbal instructions and target location interacted
      to influence reaching movement of the less-affected limb in participants with and
      without unilateral cerebrovascular accidents (CVAs). METHOD: Using a
      counterbalanced repeated-measures design, 26 people with CVA and 24 age-matched
      healthy people performed the reaching tasks under 4 conditions formed by the
      crossing of verbal instructions (speed and accuracy emphasis) and target
      locations (ipsilateral and contralateral to the performing hand). RESULTS: In the
      control groups, speeded instructions and ipsilateral reaches elicited
      significantly more preprogrammed movements than did accuracy instruction and
      contralateral reaches, respectively. Similar patterns of performance in response
      to task constraints were found in the CVA groups except for movement initiation
      in the right CVA group. CONCLUSION: Instruction and locations interacted to
      constrain reaching movements in both control and CVA groups. The combination of
      speeded instruction and ipsilateral reach may optimize movement performance of
      the less-affected limb in stroke patients.

PMID- 18712009
TI  - Task-specific, patient-driven neuroprosthesis training in chronic stroke: results
      of a 3-week clinical study.
AB  - OBJECTIVE: We examined the efficacy of a clinically based regimen in which a
      woman 16 months' poststroke participated in daily practice sessions of valued
      activities of daily living (ADLs). A unique aspect of this intervention was that
      it was largely patient driven, with the patient practicing ADLs while wearing an
      electrical stimulation neuroprosthesis. METHOD: The Fugl-Meyer Assessment (FM),
      Action Research Arm Test (ARA), Arm Motor Activity Test (AMAT), and Canadian
      Occupational Performance Measure (COPM) were administered before intervention.
      Therapy consisted of 3-hr ADL training sessions every weekday during a 3-week
      period using a neuroprosthesis featuring functional electrical stimulation during
      treatment sessions. One week after the end of the treatment phase, the FM, ARA,
      AMAT, and COPM were again administered. RESULTS: The patient exhibited reduced
      impairment (FM score change from 31 to 35), decreased time needed to complete
      AMAT tasks (from 998 s to 558 s), and increased ARA score (from 27 to 31).
      CONCLUSIONS: Clinically meaningful changes were realized with distant or minimal
      therapist supervision, making this regimen a practical and efficacious
      alternative.

PMID- 18712010
TI  - Augmenting occupational therapy treatment of upper-extremity spasticity with
      botulinum toxin A: a case report of progress at discharge and 2 years later.
AB  - This case report summarizes occupational therapy services provided to a
      participant after botulinum toxin A (BTA) injections and her improvements 2 years
      later. The injections were performed to neutralize spasticity in the left upper
      extremity after a stroke. Along with BTA, the participant received occupational
      therapy for 12 weeks, using neurodevelopmental and biomechanical approaches and
      an activity-based home program. Spasticity decreased from a 4 to a 1 on the
      Modified Ashworth Scale (MAS) immediately after the injections. Two years after
      the injections, the MAS score ranged between 1 and 1+. Initially, the participant
      demonstrated functional limitations in areas of splint application, dressing,
      toileting, and bathing. Following BTA injections and occupational therapy, the
      participant demonstrated increased independence in all deficit areas. For this
      participant, BTA, combined with functional, activity-based occupational therapy
      interventions, was associated with neurological change and greater functional use
      of the spastic limb.

PMID- 18712011
TI  - Concepts in clinical scholarship. Research literature in occupational therapy,
      2001-2005.
AB  - One method to determine trends in occupational therapy research is to survey the
      literature published in occupational therapy journals. This study describes the
      types and topics of articles published in five prominent occupational therapy
      journals over a 5-year span. Feature articles published between 2001 and 2005
      were analyzed to determine the types of articles and research and subject areas.
      The percentage of research articles published between 2001 and 2005 increased
      from 65% to 78% of all articles published and is higher than previous reports.
      More than 70% of the research articles used designs that substantially contribute
      to the evidence base for occupational therapy (defined by Kielhofner, Hammel,
      Finlayson, Helfrich, & Taylor [2004] as correlational-comparison, experimental,
      qualitative, and meta-analysis). Of the research articles, 60% addressed
      pediatric, physical disability, and rehabilitation topics. The 5-year period
      showed a trend of increasing frequency of geriatric and pediatric topics in
      research reports. Scholars should emphasize research designs that build the
      evidence for occupational therapy approaches and practices and focus on research
      topics of highest value to society.

PMID- 18712012
TI  - A firm persuasion in our work. Mentors I have known (and loved).

PMID- 18712013
TI  - Patient flow getting increased scrutiny during surveys: you'll need these data.

PMID- 18712014
TI  - Surveyors finding problems with medication standards.

PMID- 18712015
TI  - What surveyors found in patient, system tracers.

PMID- 18712016
TI  - Get pressure ulcers near zero with these best practices.

PMID- 18712017
TI  - How to score an 'A' in knowledge management.

PMID- 18712018
TI  - Proposed FDA rule on sunscreens, part 2: UVA.

PMID- 18712019
TI  - Uncombable hair syndrome.

PMID- 18712020
TI  - What's eating you? Io moth (Automeris io).

PMID- 18712021
TI  - Nevus of Ota in children.
AB  - Nevus of Ota, synonymously termed oculodermal melanosis, is an uncommon dermal
      melanosis most commonly seen at birth in children of Japanese descent, though it
      can affect individuals of any age or ethnicity. The disease tends to persist and
      extend locally, becoming increasingly prominent with age, puberty, and
      postmenopausal state. Treatment should begin early after diagnosis using multiple
      sessions of laser photothermolysis to avoid darkening and extension of the
      lesion. Important associated disorders include ipsilateral glaucoma; intracranial
      melanocytosis; and rarely cutaneous, ocular, or intracranial melanoma.
      Recommendations are discussed for managing nevus of Ota in children.

PMID- 18712022
TI  - Bilateral segmental leiomyomas: a case report and review of the literature.
AB  - Cutaneous leiomyomas are benign tumors of smooth muscles. We report a rare case
      of bilateral segmental leiomyomas in an 81-year-old man. We also provide a
      concise review of the literature on leiomyomas, their associations, and genetic
      defects of multiple cutaneous and uterine leiomyomatosis (MCUL) and hereditary
      leiomyomatosis and renal cell cancer (HLRCC) syndromes.

PMID- 18712023
TI  - Larval tick infestation: a case report and review of tick-borne disease.
AB  - Tick-borne disease in the United States continues to be a threat as people
      interact with their natural surroundings. We present a case of an 8-year-old boy
      with a larval tick infestation. Ticks within the United States can carry Lyme
      disease, Rocky Mountain spotted fever (RMSF), ehrlichiosis, babesiosis,
      tularemia, tick-borne relapsing fever, and tick paralysis. These preventable
      diseases are treatable when accurately recognized and diagnosed; however, if left
      untreated, they can cause substantial morbidity and mortality. This article
      highlights the knowledge necessary to recognize, treat, and prevent tickborne
      disease.

PMID- 18712024
TI  - Pesticide-associated pemphigus vulgaris.
AB  - We present a 40-year-old man with occupation-induced pemphigus vulgaris (PV). He
      developed PV within days of a one-time heavy exposure to fumes of burning
      glyphosate, a broad-spectrum nonselective pesticide. This exposure suggests acute
      cutaneous contact as a stimulus in the development of his pemphigus. While the
      patient initially required mycophenolate mofetil and prednisone therapy, he has
      since eliminated contact with pesticides and has been successfully tapered off
      systemic medication. We discuss the case and review concepts of inducible PV by
      pesticides and physical cutaneous injury.

PMID- 18712025
TI  - Primary localized cutaneous nodular amyloidosis and CREST syndrome: a case report
      and review of the literature.
AB  - Primary localized cutaneous nodular amyloidosis (PLCNA) is a form of primary
      localized cutaneous amyloidosis (PLCA) that presents as yellowish waxy nodules on
      the extremities, face, trunk, or genitalia. We report the case of a patient with
      PLCNA and CREST (calcinosis, Raynaud phenomenon, esophageal motility disorders,
      sclerodactyly, and telangiectasia) syndrome. A diagnosis of her extensive PLCNA
      was made after biopsy specimens from the bilateral shins stained positive for
      amyloid extending from the superficial papillary dermis to the subcutis. Results
      of a workup were negative for paraproteinemia or signs of systemic amyloidosis
      and have remained so after 8 years of follow-up. We present a review of the
      literature describing the presentation and histopathology of the varying forms of
      amyloidosis.

PMID- 18712026
TI  - Acquired acrodermatitis enteropathica secondary to alcoholism.
AB  - Acrodermatitis enteropathica is a zinc deficiency disorder characterized by well
      demarcated, erythematous, eczematous plaques in a periorificial and acral
      distribution. Hereditary and acquired forms have been described. We report a case
      of acquired acrodermatitis enteropathica secondary to alcoholism. Treatment of
      the underlying disorder and zinc replacement therapy resulted in rapid resolution
      of the condition.

PMID- 18712027
TI  - Segmental neurofibromatosis associated with renal angiomyolipomas.
AB  - Segmental neurofibromatosis (SN) is a rare disorder characterized by
      neurofibromas or neurofibromas with cafe-au-lait spots limited to one region of
      the body without crossing the midline. Renal angiomyolipomas (AMLs) are rare
      benign neoplasms usually found in association with tuberous sclerosis (TS).
      Similar to neurofibromatosis (NF), TS has a high spontaneous mutation rate and a
      family history often is absent. Although both are autosomal dominant diseases
      with neural involvement, there are few reports in the literature demonstrating a
      link between the 2 disorders. We report a case of SN associated with renal AMLs.
      To our knowledge, there has been only 1 prior report of renal AML associated with
      NF type 1 (NF1), and there have been no prior reports of SN associated with AML.

PMID- 18712028
TI  - Jacquet erosive diaper dermatitis: a complication of adult urinary incontinence.
AB  - Jacquet erosive diaper dermatitis is typically described as a severe irritant
      dermatitis of the perianal region. However, Jacquet erosive diaper dermatitis,
      perianal pseudoverrucous papules and nodules, and granuloma gluteale infantum/
      adultorum have been regarded as discrete entities or all part of the same
      clinical spectrum, representing the result of chronic, severe, irritant contact
      dermatitis. We present a case of Jacquet erosive diaper dermatitis and a
      discussion of the clinical spectrum of diseases to which it belongs.

PMID- 18712030
TI  - John Halamka, M.D., MS. CIO, CareGroup Healthcare System.

PMID- 18712029
TI  - A new standardized method of evaluating cutaneous irritation from topical
      medications.
AB  - We used a new technique to evaluate and compare cutaneous irritation from various
      topical medications. Twenty participants with corticosteroid-responsive
      dermatoses were enrolled. Three target areas of unaffected skin were abraded. A
      negative control (petrolatum ointment), a positive control (an over-the-counter
      [OTC] anti-itch preparation containing benzyl alcohol), and a test product
      (fluticasone propionate lotion 0.05%) were each applied to separate targetareas
      on the legs. Participants rated the irritation of each target area using a 10
      point scale (1 [no symptoms] to 10 [intolerable burning/ stinging requiring
      removal of the medication]). The mean irritation scores for petrolatum ointment,
      the OTC anti-itch preparation, and fluticasone propionate lotion 0.05% were 1.20,
      6.15, and 2.05, respectively. The difference in irritation between the OTC anti
      itch preparation and fluticasone propionate lotion 0.05% was highly significant
      (P < .0001). The difference in irritation between the OTC anti-itch preparation
      and petrolatum ointment also was highly significant (P < .0001). The difference
      in irritation between fluticasone propionate lotion 0.05% and petrolatum ointment
      also was statistically significant (P = .0104). Irritation scores were then
      standardized on a 10-point scale, with the irritation score of the negative
      control given a value of 1.00 and the irritation score of the positive control
      given a value of 10.00. The standardized irritation score of the test product,
      fluticasone propionate lotion 0.05%, was calculated to be 2.55. Our assay was
      able to detect and quantify even minimal cutaneous irritation secondary to
      application of topical medications.

PMID- 18712031
TI  - Automated informed consent. Protecting patients from wrong-site surgery and
      medication errors is priority number one for this lone star state cancer center.

PMID- 18712032
TI  - Transforming Healthcare. A top U.S. hospital implements CPOE and improves patient
      safety while dramatically reducing turn-around time.

PMID- 18712033
TI  - Protecting the pharmaceutical supply chain. Ensuring an unbroken supply of
      pharmaceuticals can save lives during times of disaster.

PMID- 18712034
TI  - Web welcome mat. A pediatrics practice updates its web site to maximize patient
      and provider communications.

PMID- 18712035
TI  - If you build it, don't expect them to come. There's a problem with imposing top
      down HIEs on localized healthcare communities. They may not work.

PMID- 18712036
TI  - Plasma adiponectin is associated with plasma brain natriuretic peptide and
      cardiac function in healthy subjects.
AB  - The aim of this study was to evaluate the relationship between the plasma
      adiponectin level, plasma brain natriuretic peptide (BNP) level, and cardiac
      function in healthy subjects. We obtained clinical data and performed blood
      tests, including measurement of the plasma adiponectin and BNP levels, in 1,538
      healthy persons from Arita-cho, a rural area of Japan. Six hundred and eight
      subjects also underwent echocardiography. There was a significant positive
      correlation between their plasma BNP and adiponectin levels in simple regression
      analysis (standardized regression coefficient [beta] = 0.34). Multivariate
      regression analysis revealed that the plasma adiponectin level was independently
      associated with the plasma BNP level (beta = 0.12), as well as with the age (beta
      = 0.22), male gender (beta = -0.26), waist circumference (beta = -0.16), and the
      plasma levels of high-density lipoprotein cholesterol (beta = 0.13),
      triglycerides (beta = -0.16), aspartate aminotransferase (beta = 0.08), gamma
      glutamyl transpeptidase (beta = -0.10), uric acid (beta = -0.07), and creatinine
      (beta = 0.08). We also found a link between plasma adiponectin and the left
      atrial diameter index (beta = 0.08) or left ventricular diameter index (beta =
      0.11), even after adjustment for age, sex, and body mass index. The plasma
      adiponectin level increased along with an increase of plasma BNP in healthy
      subjects independently of other confounding factors, demonstrating that
      adiponectin reflects cardiac function.

PMID- 18712037
TI  - Family history of hypertension and arterial elasticity characteristics in healthy
      young people.
AB  - Family history of hypertension is a primary predictor of high blood pressure
      (BP). This study attempted to determine whether there is a gradual increase in BP
      and an early change in arterial elasticity characteristics between young healthy
      individuals with or without a family history of hypertension and whether or not
      this increase is apparent in males as well as in females. A total of 270
      normotensive healthy individuals (112 men and 158 women, aged 16 to 30 years)
      with or without a family history of hypertension, participated in conventional BP
      measurement and completed questionnaires covering basic information and a
      detailed family history of cardiovascular disease. Large arterial (capacitive)
      compliance (C1) and small arterial (oscillatory or reflective) compliance (C2)
      were derived from HDI/PulseWave CR-2000 (Hypertension Diagnostics, Minneapolis,
      USA). Based on family history information about parents and grandparents, three
      groups were formed: subjects with at least one hypertensive parent (group A),
      subjects with only hypertensive grandparents (group B), and subjects with
      normotensive parents and grandparents (group C). Men in group A had lower C1 and
      C2 along with higher systolic BP (SBP), diastolic BP (DBP), and heart rate than
      men in group C. Those in group B had intermediate C1, C2 and BP levels. C1 had a
      linear relationship with SBP, DBP, and heart rate. In the logistic regression
      model of family history of hypertension, C2 was lower in young normotensive males
      with parental hypertension (B = -0.315, exp B = 0.73, p = 0.03), independently of
      SBP, DBP, and heart rate. Among females, subjects with parental hypertension had
      higher systolic, mean arterial pressure, and pulse pressure (p < 0.05), and there
      were no significant differences in C1 and C2 between those with and those without
      parental hypertension. In conclusion, compared with normotensive offspring of
      normotensive parents, normotensive offspring of hypertensive parents had
      increased BP and impaired arterial properties, namely large and small arterial
      compliance as measured noninvasively by HDI. These differences were exhibited
      conspicuously in men but not in women. Alteration in arterial function in young
      non-hypertensive subjects may be a risk factor for hypertension and may
      contribute to the progression to hypertension later in life.

PMID- 18712038
TI  - Comparison of renal and vascular protective effects between telmisartan and
      amlodipine in hypertensive patients with chronic kidney disease with mild renal
      insufficiency.
AB  - The present study was conducted to compare the renal and vascular protective
      effects of telmisartan and amlodipine in untreated hypertensive chronic kidney
      disease (CKD) patients with moderate renal insufficiency. Thirty hypertensive CKD
      patients were randomly assigned to receive telmisartan 40 mg (n = 15) or
      amlodipine 5 mg (n = 15) once daily for 12 months. Changes in blood pressure,
      serum creatinine, 24-h creatinine clearance (Ccr), proteinuria, brachial-ankle
      pulse wave velocity (baPWV), intima-media thickness (IMT), plasma interleukin-6
      (IL-6), plasma matrix metalloproteinase (MMP)-9 and lipid profiles were monitored
      in all patients. Before treatment, there were no significant differences in these
      parameters between the telmisartan and amlodipine groups. Over the 12 month
      observation period, blood pressure decreased equally in both groups. However,
      serum creatinine, proteinuria, baPWV, IMT, plasma levels of IL-6 and MMP-9 and
      total cholesterol decreased and 24-h Ccr increased more strikingly in the
      telmisartan group than the amlodipine group. These data suggest that telmisartan
      is more effective than amlodipine for protecting renovascular functions, and
      potentially for ameliorating atherosclerosis, in hypertensive CKD patients with
      moderate renal insufficiency.

PMID- 18712039
TI  - Body fat distribution and the risk of hypertension and diabetes among Japanese
      men and women.
AB  - To identify anthropometrical indices of body fat distribution for predicting the
      risk of hypertension and diabetes, a population-based prospective study was
      designed. Subjects in two communities (n = 2,422 and 3,195), who were free of
      hypertension and diabetes, respectively, were followed-up. The area and gender
      specific risk of hypertension and diabetes were compared among tertiles of body
      mass index (BMI) and body fat distribution, including waist circumference (WC),
      waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and subscapular skinfold
      thickness (SSF). During the 10-year follow-up for hypertension and diabetes, the
      incident cases of hypertension were 72 for Yao men, 125 for Kyowa men, 160 for
      Yao women and 193 for Kyowa women and those of diabetes were 27, 64, 37 and 77,
      respectively. One SD differences in BMI and WC were associated with 1.2 to 1.6
      fold higher risk of hypertension, and that of SSF was associated with 1.4 to 1.6
      fold higher risk of diabetes for both men and women in Yao and for women, but not
      men, in Kyowa. One SD differences of BMI, WC and WHtR were also associated with
      1.4 to 2.0-fold higher risk of diabetes for Yao and Kyowa women. In conclusion,
      the significant predictors for hypertension were BMI and WC and those for
      diabetes were BMI and SSF in both genders in both communities, except for men in
      Kyowa. WC and WHtR were also predictors for diabetes in women but not in men.

PMID- 18712040
TI  - Toll-like receptor 4 gene polymorphisms and preeclampsia: lack of association in
      a Caucasian population.
AB  - Preeclampsia is a multifactorial disorder with genetic and environmental
      components. As Toll-like receptor 4 (TLR4) has an essential role in innate immune
      response, which is exaggeratedly activated in preeclampsia, our aim was to
      investigate whether two single nucleotide polymorphisms (SNPs) of the TLR4 gene-
      Asp299Gly (A896G) and Thr399Ile (C1196T)--are associated with preeclampsia in a
      Caucasian population from Hungary. In a case-control study, we analyzed blood
      samples from 180 preeclamptic patients and 172 normotensive, healthy pregnant
      women with the polymerase chain reaction (PCR)-restriction fragment length
      polymorphism (RFLP) method. The linkage disequilibrium (LD) profile of the TLR4
      gene was investigated and tag SNPs were identified using data from the
      International HapMap Project. There were no significant differences in the
      genotype and allele frequencies of Asp299Gly and Thr399Ile polymorphisms between
      the two study groups. Additionally, no significant difference was found in the
      distribution of the estimated haplotypes created by the two polymorphisms between
      the preeclamptic and the control group. Furthermore, no significant differences
      were detected in the genotype, allele and haplotype frequencies of Asp299Gly and
      Thr399Ile TLR4 SNPs between patients with mild and severe preeclampsia, between
      patients with late and early onset of the disease, or between preeclamptic
      patients with and without fetal growth restriction. In conclusion, we did not
      find an association between TLR4 Asp299Gly and Thr399Ile gene polymorphisms and
      preeclampsia. As the Thr399Ile polymorphism is a highly informative tag SNP of
      the TLR4 gene, our results suggest that variations in this genomic region are not
      associated with preeclampsia. Nevertheless, further studies are required with
      determination of fetal TLR4 genotypes to explore the role of TLR4 gene
      polymorphisms in the risk of preeclampsia, especially in ethnically different
      populations.

PMID- 18712041
TI  - Pattern of 24-hour ambulatory blood pressure monitoring in type 2 diabetic
      patients with cardiovascular dysautonomy.
AB  - The pathophysiological mechanisms linking cardiovascular dysautonomy to mortality
      are unclear. The aim of this study was to investigate the pattern of 24-h
      ambulatory blood pressure (BP) monitoring (ABPM) in diabetic patients with
      cardiovascular autonomic neuropathy (CAN). We evaluated 391 type 2 diabetic
      patients in a cross-sectional study. Five clinical tests of CAN were performed:
      heart-rate variation during deep breathing, the Valsalva maneuver, and standing,
      and BP variation during handgrip and standing. Patients were considered to have
      initial CAN if one heart-rate test was abnormal or two were borderline, and to
      have definite or severe CAN if at least two tests were abnormal. Differences
      between patients with and without CAN were assessed by bivariate tests and
      ANCOVA. Of the 391 patients, 230 (59%) presented clinical CAN, of whom 53 had
      definite or severe involvement. Patients with CAN were older, had diabetes of
      longer duration, and had an equal prevalence of hypertension but used more
      antihypertensive drugs than those without CAN. On ABPM, patients with definite or
      severe CAN had higher systolic BP (SBP) and pulse pressures (PP) than those
      without CAN, particularly in the nighttime (SBP: 128 +/- 18 vs. 117 +/- 16 mmHg,
      p = 0.007; PP: 58 +/- 13 vs. 50 +/- 11 mmHg, p = 0.003) and early morning (SBP:
      140 +/- 18 vs. 131 +/- 17 mmHg, p = 0.05) after adjustment for potential
      confounders, as well as a higher prevalence of the systolic nondipping pattern
      (75.5% vs. 50.9%, p = 0.021). In conclusion, type 2 diabetic patients with more
      severe CAN have higher SBP and PP, especially during the nighttime and early
      morning, as well as a higher prevalence of nondipping status. This unfavorable 24
      h ABPM pattern may contribute to the increased cardiovascular risk of diabetic
      patients with dysautonomy.

PMID- 18712042
TI  - Vascular permeability, blood pressure, and organ damage in primary hypertension.
AB  - Sub-clinical organ damage is a strong independent predictor of cardiovascular
      mortality in primary hypertension, and its changes over time parallel those in
      risk of cardiovascular events. A better understanding of the pathogenetic
      mechanisms underlying the development of target organ damage may help us devise
      more effective therapeutic strategies. We therefore investigated the relationship
      between the presence of organ damage and some of its potential determinants, such
      as blood pressure severity and early atherosclerotic abnormalities. Thirty-seven
      untreated, non-diabetic hypertensive patients were enrolled. Target organ damage
      was assessed by albuminuria and left ventricular mass index; systemic vascular
      permeability was evaluated by transcapillary escape rate of albumin (TERalb); and
      blood pressure was measured by 24h ambulatory blood pressure monitoring. The
      albumin-to-creatinine ratio and left ventricular mass index were directly related
      to TERalb (r = 0.48, p = 0.003 and r = 0.39, p < 0.020, respectively) and 24-h
      systolic blood pressure values (r = 0.54, p < 0.001; r = 0.60, p < 0.001). The
      simultaneous occurrence of increased blood pressure load and TERalb was
      associated with higher left ventricular mass index values (p = 0.012) and
      entailed an increased risk of having at least one sign of damage (chi2 = 17.4; p
      < 0.001). Logistic regression analysis showed that the risk of presenting at
      least one sign of organ damage increased more than ten-fold when TERalb was above
      the median and more than five-fold with each 10 mmHg increase in 24-h systolic
      blood pressure. Blood pressure load and vascular permeability are potentially
      modifiable factors that are independently associated with the occurrence of sub
      clinical signs of renal and cardiac damage in hypertensive patients.

PMID- 18712043
TI  - Angiographic index for angioplasty-treatable atheromatous renal artery stenosis.
AB  - The relative reduction of the lumen diameter by an atheromatous lesion (%
      diameter reduction) is generally used as an angiographic index for atheromatous
      renal artery stenosis (ARAS), but its association with the clinical outcome of
      angioplasty has not been sufficiently evaluated. This study aimed to identify an
      angiographic index(ices) that can be used to identify angioplasty-treatable ARAS.
      We evaluated the clinical outcome of angioplasty in 27 patients who had
      unilateral ARAS without renal insufficiency by assessing the reduction in
      systemic arterial blood pressure (BP) after angioplasty and examined its
      association with various angiographic indices. In the receiver operating
      characteristic analysis for BP reduction, the area under the curve was larger for
      the absolute value of the lumen diameter at the narrowest part of its
      constriction (the narrowest diameter), an angiographic index introduced in this
      study, than for % diameter reduction (0.770 vs. 0.731). At a 3-mm maximum
      threshold, the narrowest diameter identified cases with BP reduction; the
      sensitivity/specificity was 0.89/0.75 (p < 0.001). Furthermore, the narrowest
      diameter correlated better than % diameter reduction with hemodynamic indices of
      ARAS. In conclusion, the narrowest diameter is an angiographic index that can
      effectively identify angioplasty-treatable ARAS in patients without renal
      insufficiency.

PMID- 18712044
TI  - Effects of strict blood pressure control by a long-acting calcium channel blocker
      on brain natriuretic peptide and urinary albumin excretion rate in Japanese
      hypertensive patients.
AB  - Strong adherence to antihypertensive therapy has been shown to reduce the
      frequency of cardiovascular events by strictly controlling blood pressure.
      Although calcium channel blockers (CCBs) are among the most popular
      antihypertensive drugs in Japan, few trials have been conducted using high CCB
      doses in Japanese patients. In this study, we administered amlodipine 5 mg or 10
      mg to patients with hypertension in order to compare the efficacy and
      tolerability of low and high doses, and measured two surrogate markers of
      hypertensive target organ damage, i.e., brain natriuretic peptide (BNP) as a risk
      marker of cardiac overload and microalbuminuria as a measure of renal damage.
      Seventy-two patients were randomly assigned to either amlodipine 5 mg (n = 35) or
      10 mg (n = 37) dose groups. The latter group achieved greater reductions in
      clinic as well as both morning and evening home BP levels without an increase in
      pulse rate (the differences between the two groups in clinic/morning/evening
      systolic BP were 4.7/4.7/5.4 mmHg, and for diastolic BP they were 4.2/3.6/3.8
      mmHg). Reductions in BNP and urinary albumin/creatinine ratio (UAR) levels were
      significantly correlated with the reductions in systolic BP levels (BNP,
      clinic/morning BP: r = 0.256, p = 0.030/r = 0.330, p = 0.005; UAR, clinic BP: r =
      0.316, p = 0.007). In conclusion, the higher dose (10 mg) of amlodipine induced
      greater reductions in all BP levels than did the lower dose, without increasing
      the pulse rate. These additional reductions were significantly correlated with
      reductions in hypertensive cardiac overload, as evaluated by BNP levels, and a
      reduction in renal damage, as evaluated by microalbuminuria levels. Moreover, a
      reduction in the microalbuminuria may have occurred concomitant with a reduction
      in clinic systolic BP level.

PMID- 18712045
TI  - Population-based study on the prevalence and correlates of orthostatic
      hypotension/hypertension and orthostatic dizziness.
AB  - There are no epidemiological studies of orthostatic hypotension (OH)/hypertension
      (OHT) and orthostatic dizziness (OD) in adults across all age groups. The aim of
      this study is to examine the prevalence and correlates of OH, OHT, and OD in
      community dwellers aged > or = 20 years. OH was defined as a decline in systolic/
      diastolic blood pressure of > or = 20/10 mmHg when a person stood up from a
      supine position. OHT was a postural increase of > or = 20 mmHg in systolic blood
      pressure. OD was dizziness, lightheadedness, or faintness as the person stood up.
      A total of 1,638 adults were included. Subjects were classified as normotensive,
      pre-hypertensive, or hypertensive. The prevalences of OH, OHT, and OD were 15.9,
      1.1, and 4.8%, respectively. OD was associated with neither OH nor OHT. None of
      the subjects aged < 40 had OHT; hypertension (p = 0.030) and female gender (p <
      0.001) were the independent correlates of OH and OD, respectively, in that age
      range. For subjects aged > or = 40 years, age (p = 0.003), pre-hypertension (p =
      0.024), hypertension (p = 0.008), and diabetes mellitus (p = 0.036) were
      independently related to OH. Age (p < 0.001) and supine systolic blood pressure
      (p = 0.023) were the correlates of OHT. Female gender (p < 0.001) and
      sedatives/hypnotics (p = 0.040) were associated with OD. In conclusion, age, pre
      hypertension, hypertension, and diabetes mellitus were important determinants of
      OH. OD was more prevalent in women and in subjects using sedatives/hypnotics. The
      risk of OHT increased with age and with supine systolic blood pressure in adults
      aged > or = 40 years. OH and OHT cannot be determined solely from the presence of
      OD because of their dissociation.

PMID- 18712046
TI  - Natural variances in blood pressure category among Chinese adults.
AB  - Little is known about the natural progression and regression of blood pressure
      status, even though such knowledge would help determine the best intervention
      strategies. Our study aimed to explore natural changes in blood pressure status
      in a middle-aged Chinese population. A total of 6,129 Chinese men and women, aged
      35 to 59 years at baseline, from the China Multi-center Collaborative Study of
      Cardiovascular Epidemiology, were reexamined 6 years later to determine the
      probability of progression (from non-hypertension to hypertension) and regression
      (from hypertension to non-hypertension). The majority (80%) of non-hypertensives
      among the respondents in this study remained normal or pre-hypertensive; about
      two-thirds of stage 1 hypertensives either stayed at the same stage or regressed
      to non-hypertension. However, only 9% of stage 2 hypertensives regressed to non
      hypertension. Multi-variable logistic regression analysis showed that the stage 1
      hypertension group had a 5-fold chance of regressing to non-hypertension in
      comparison with the stage 2 hypertension group (odds ratio [OR] = 0.2, 95%
      confidence interval [CI]: 0.1-0.3), whereas the pre-hypertension group had a 4
      fold likelihood of progressing to hypertension compared with normotensive
      subjects (OR = 4.4, 95% CI: 3.7-5.3). After excluding participants ever on drug
      treatment in either examinations, the OR of regression for stage 2 hypertension
      was over twice that for stage 1 hypertension (OR = 0.5, 95% CI: 0.3-0.7), and the
      possibility of progression decreased, though very slightly (OR = 4.3, 95% CI: 3.6
      5.1). Weight change significantly influenced progression and regression. Alcohol
      drinking affected progression significantly. In conclusion, the present findings
      support the strategy of intensively treating stage 2 hypertension and moderately
      treating stage 1 hypertension. Persons with pre-hypertension should be monitored
      for progression and advice on lifestyle modifications should be used.

PMID- 18712047
TI  - Presence of chronic kidney disease and subsequent changes of left ventricular
      geometry over 4 years in an apparently healthy population aged 60 and older.
AB  - Chronic kidney disease (CKD) is associated with increased cardiovascular (CV)
      risk. Left ventricular geometry (LVG) is a predictor for CV events. However, the
      influence of CKD on LVG changes in the elderly remains unclear. In this study, we
      performed echocardiography to evaluate LVG at baseline and at 2 and 4 years after
      baseline in 120 apparently healthy elderly Chinese who were recruited from a
      screening of 1,500 individuals. No subjects had a history of organic heart
      disease or chronic medication. CKD was defined as a glomerular filtration rate
      (GFR) of less than 60 mL/min/1.73 m2, as calculated using the Modification of
      Diet in Renal Disease (MDRD) study equation. The mean age was 71.5 +/- 3.9 years
      (range: 60-81 years). The prevalences of CKD, concentric remodeling, eccentric
      hypertrophy and concentric hypertrophy were significantly increased after 4 years
      (all p < or = 0.033). The LVG changes were only significant in subjects with CKD
      at baseline (p = 0.039). If we stratified subjects into those with favorable
      (normal and concentric remodeling) and those with unfavorable LVG (eccentric
      hypertrophy and concentric hypertrophy), the presence of CKD was an independent
      predictor for unfavorable LVG after 4 years both in univariate and multivariate
      analysis (odds ratio [OR] = 3.18 and 3.70, p = 0.011 and 0.015, respectively).
      This longitudinal study showed that aging was related to increased prevalence of
      CKD and changes of LVG. The presence of CKD is associated with changes of LVG
      toward unfavorable forms. These findings might partially explain why subjects
      with CKD have a higher CV risk and could provide knowledge essential to the
      assessment of cardiac structure and disease in older subjects.

PMID- 18712048
TI  - Comparison of the effects of telmisartan and olmesartan on home blood pressure,
      glucose, and lipid profiles in patients with hypertension, chronic heart failure,
      and metabolic syndrome.
AB  - We compared the effects of telmisartan and olmesartan in 20 patients with chronic
      heart failure and metabolic syndrome. The subjects underwent once-daily 40 mg
      telmisartan for at least 3 months before switching to once-daily 20 mg olmesartan
      for the next 3 months (post 1). They were then treated with 3 months of once
      daily 40 mg telmisartan (post 2). Systolic and diastolic blood pressure in the
      early morning, plasma B-type natriuretic peptide, serum total cholesterol, low
      density lipoprotein cholesterol, and triglyceride levels were increased at post 1
      (p < 0.005, p < 0.05, p < 0.05, p < 0.05, p < 0.05, and p < 0.005 vs. baseline,
      respectively) before returning to their baseline values at post 2. The changes in
      plasma B-type natriuretic peptide levels correlated significantly with the shifts
      in systolic and diastolic blood pressure in the early morning at posts 1 and 2.
      Meanwhile, there were no fluctuations in either blood pressure in the late
      evening or in the outpatient room; nor were there fluctuations in heart rate.
      Simultaneously, neither serum high-density lipoprotein cholesterol nor fasting
      blood sugar levels differed significantly between posts. Moreover, telmisartan
      had more beneficial effects on glucose and lipid profiles in patients with
      relatively high HbA1c, serum total and low-density lipoprotein cholesterol, and
      triglyceride levels. Therefore, we concluded that telmisartan was more beneficial
      than olmesartan for controlling blood pressure in the early morning, as well as
      for improving glucose and lipid profiles in patients with hypertension, chronic
      heart failure, and metabolic syndrome.

PMID- 18712049
TI  - Associations of hypertension and its complications with variations in the
      xanthine dehydrogenase gene.
AB  - Hyperuricemia and oxidative stress participate in the pathophysiology of
      hypertension and its complications. Xanthine dehydrogenase (XDH) produces urate
      and, in its oxidase isoform, reactive oxygen species. Here we have studied
      whether or not the genetic variations in XDH could be implicated in hypertension
      and its complications. By sequencing the promoter region and all exons of XDH in
      48 subjects, we identified three missense mutations (G172R, A932T, N1109T) in a
      heterozygous state in addition to 34 variations, including 15 common single
      nucleotide polymorphisms (SNPs). The three missense mutations and eight common
      SNPs (11488C>G, 37387A>G, 44408A>G, 46774G>A, 47686C>T, 49245A>T, 66292C>G, and
      69901A>C) were genotyped in 953 hypertensive Japanese subjects and in 1,818
      subjects from a general Japanese population. Four hypertensive patients with rare
      missense mutations (G172R or N1109T) in homozygous form had severe hypertension.
      Multivariate logistic regression analysis showed a significant association of
      three SNPs with hypertension in men: 47686C>T (exon 22, odds ratio [OR]: 1.52, p
      = 0.047) and 69901A>C (intron 31, OR: 3.14, p = 0.039) in the recessive model,
      and 67873A>C (N1109T) (exon 31, OR: 1.84, p = 0.018) in the dominant model. After
      full adjustment for all confounding factors, only one polymorphism (69901A>C) was
      found to be associated with carotid atherosclerosis in the dominant model (p =
      0.028). Multiple logistic regression analysis showed that one SNP (66292C>G) was
      significantly associated with chronic kidney disease (CKD: estimated creatinine
      clearance < 60 ml/min) in the recessive model (p = 0.0006). Our results suggest
      that genetic variations in XDH contribute partly to hypertension and its
      complications, including atherosclerosis and CKD.

PMID- 18712050
TI  - Myocardial gene expression associated with genetic cardiac hypertrophy in the
      absence of hypertension.
AB  - The hypertrophic heart rat (HHR) was derived from the spontaneously hypertensive
      rat of the Okamoto strain and develops cardiac hypertrophy in the absence of
      hypertension. The genetic basis of this hypertrophy is unknown. Therefore, we
      compared gene expression profiles in the left ventricular myocardium of young (8
      10 weeks of age) and old (38-50 weeks) HHR with rats from an age-matched control
      strain, the normal heart rat (NHR). cDNA microarrays (National Institute of Aging
      [NIA], 15,247 clones) were used to evaluate gene expression in cardiac-derived
      Cy3 and Cy5 labeled cDNA. M values (log2[Cy5/Cy3]) were obtained and significant
      differential expression was identified using an empirical Bayesian approach with
      specific results verified using real-time PCR. Compared with NHR, HHR cardiac
      weight index (heart weight/ body weight) was significantly elevated at both ages
      (young: 5.5 +/- 0.5 vs. 3.9 +/- 0.2; old: 4.2 +/- 0.3 vs. 3.4 +/- 0.2 mg/g; p <
      0.05) with no difference in body weight or in tail-cuff blood pressure detected
      between the strains at either age. Differential expression was observed in 65 and
      390 clones in young and old HHR, respectively, with more genes exhibiting down
      regulation than up-regulation in both instances (young: down 44 vs. up 21; old:
      down 292 vs. up 98). Our data suggest a role for the Ras/mitogen-activated
      protein kinase (MAPK) signaling pathway and the tumor necrosis factor (TNF)
      receptor-mediated activation of nuclear factor-kappaB (NF-kappaB) in the etiology
      of cardiac enlargement in the HHR. These findings support the candidature of
      previously identified cardiotrophic agents in contributing to the cardiac
      enlargement in the normotensive HHR, and also identify novel genetic factors
      which may be involved in the genesis of primary cardiac hypertrophy.

PMID- 18712051
TI  - Effects of soy protein hydrolysate on blood pressure and angiotensin-converting
      enzyme activity in rats with chronic renal failure.
AB  - We investigated the effects of soy protein and soy protein hydrolysate on blood
      pressure control, angiotensin-converting enzyme (ACE) activity, and renal
      function in a rat chronic renal failure model. Rats that had undergone a 5/6
      nephrectomy were separated into three groups and fed different experimental diets
      for 14 weeks. At the end of the study, rats that fed a diet containing soy
      protein as the protein source had better blood pressure control and renal
      function, as well as lower circulating ACE activity and renal tumor-necrosis
      factor-alpha (TNF-alpha) concentration than rats fed a casein protein diet. Soy
      protein hydrolysate was shown to be as effective as soy protein in preventing the
      elevation of blood pressure, the progression of renal failure, and decreases in
      kidney TNF-alpha level, plasma ACE activity, and insulin concentration. In
      conclusion, the beneficial effects of consuming soy protein on blood pressure and
      renal function may be mediated mostly by its pepsin-digested hydrolysate through
      its ACE inhibitory activity.

PMID- 18712052
TI  - Effects of rosiglitazone (a peroxysome proliferator-activated receptor gamma
      agonist) on the blood pressure and aortic structure in metabolically programmed
      (perinatal low protein) rats.
AB  - This study investigated the effects of rosiglitazone on nutritionally programmed
      chronic disease, with a focus on blood pressure (BP) and aortic wall structural
      remodeling. Wistar pregnant rats were fed one of two diets: a normal protein diet
      (19% protein; NP rats) or low-protein diet (5% protein; LP rats). Male offspring
      at 3 months of age were randomly divided into four groups: NP offspring treated
      with rosiglitazone (NPR); untreated NP offspring (NP); LP offspring treated with
      rosiglitazone (LPR); untreated LP offspring (LP). Rosiglitazone was administered
      at a dose of 5 mg/kg/d until 6 months of age. BP was elevated in LP offspring.
      Rosiglitazone reduced BP beginning in the first week of treatment in the LPR
      offspring. The insulin sensitivity was increased in LP offspring, and was not
      altered by rosiglitazone. LP offspring exhibited a 40% reduction in the amount of
      elastic fibers in the aorta wall compared with NP offspring (p < 0.01), and the
      quantity of elastic fibers was not altered by rosiglitazone. The smooth muscle
      cells, elastic lamellae, circumferential wall tension (CWT) and tensile stress
      (TS) were increased in LP offspring, indicating increased blood flow in the
      aorta. Rosiglitazone reduced both CWT and TS by 30% compared to the levels in
      untreated LP offspring (p < 0.01 for both). Rosiglitazone restored the
      expressions of angiotensin II type 1 receptor and endothelial nitric oxide
      synthase nearly to the levels in the NP offspring. ANOVA disclosed a significant
      two-factor interaction between protein content in the diet and rosiglitazone
      treatment (p < 0.001 for CWT and p < 0.00001 for TS, two-way ANOVA). We conclude
      that rosiglitazone has beneficial effects in reducing the BP and the aortic
      tunica media hypertrophy with consequent balance of the wall stress in
      metabolically programmed offspring.

PMID- 18712053
TI  - Immobilization stress inhibits intimal fibromuscular proliferation in the process
      of arterial remodeling in rats.
AB  - We investigated role of beta-endorphin (END), which is released by immobilization
      stress, on intimal fibromuscular proliferation in a rat model of arterial
      remodeling after intimal injury. The endothelium of the abdominal aorta of Wistar
      Kyoto rats was denuded, and the rats were subjected to immobilization stress (6
      h/d), which raised the serum concentration of END, and intraperitoneal
      administration of either END (20 ng/kg/d) or naltrexone (NAL: 4 mg/kg/d). The
      proliferative activity (PA) of medial smooth muscle cells (SMCs) and the
      intima/media area ratio (R) were determined at 3 and 14 d after denudation,
      respectively. PA and R were significantly reduced by immobilization (PA: 64.8%,
      R: 34.6%), and NAL treatment completely reversed the decreases in PA and R. On
      the other hand, END reduced both PA and R (PA: 21.7% and R: 24.9%), and NAL also
      reversed the decreases in PA and R. END (20 pg/mL) inhibited both the
      proliferation (79% at 96 h) and migration (26%) of SMCs cultured with 5% fetal
      bovine serum in vitro, and NAL (100 microg/mL) reversed the inhibition of both
      activities. Our results suggest that immobilization stress stimulates the release
      of endogenous END, which then prevents both proliferation and migration of medial
      SMCs after intimal injury.

PMID- 18712054
TI  - Angiotensin II-induced osteopontin expression in vascular smooth muscle cells
      involves Gq/11, Ras, ERK, Src and Ets-1.
AB  - Recent studies suggest that osteopontin (OPN) plays a critical role in the
      progression of atherosclerotic plaques and that angiotensin II (Ang II) is a
      potent upregulator of OPN expression. The goal of the present study was to
      characterize the signaling mechanisms whereby Ang II increases OPN expression in
      vascular smooth muscle cells (VSMC). YM-254890, a specific inhibitor of G(q/11),
      potently suppressed Ang II-induced OPN expression and ERK1/2 activation. Among
      dominant-negative (DN) mutants of small G proteins, only DN-Ras suppressed Ang II
      induced OPN promoter activity. DN-MEK1 markedly inhibited Ang II-induced OPN
      promoter activity, while neither DN-JNK nor DN-p38 MAP kinase had any effect. DN
      Src and DN-Fyn suppressed Ang II-induced OPN promoter activity. YM-254890
      inhibited Ang II-induced Src and Ras activation, and PP2, a selective inhibitor
      for the Src kinase family, inhibited Ras activation, suggesting that the G(q/11)
      Src-Ras axis is the upstream signaling cascade for Ang II-induced OPN expression.
      Finally, small interfering RNA against Ets-1 suppressed Ang II-induced OPN
      expression. In conclusion, these data suggest that Ang II-induced OPN expression
      in VSMC is mediated by signaling cascades involving G(q/11) the Ras-ERK axis, and
      the Src kinase family, and by the transcription factor, Ets-1. These signaling
      molecules may represent therapeutic targets for the prevention of pathological
      vascular remodeling.

PMID- 18712055
TI  - Cholesterol reduction and atherosclerosis inhibition by bezafibrate in low
      density lipoprotein receptor knockout mice.
AB  - Fibrates, peroxisome proliferator-activated receptor a agonists, are widely used
      as lipid-lowering agents with anti-atherogenic activity. However, conflicting
      results have been reported with regard to their pharmacological effects on plasma
      lipoprotein profiles as well as on atherosclerosis in animal models. Furthermore,
      the anti-atherogenic effects of bezafibrate, one of the most commonly used
      fibrates, in animal models have not been reported. In the present study, we
      investigated the effects of bezafibrate on lipoprotein profiles as well as on
      atherosclerosis in low-density lipoprotein receptor knockout (LDLR-/-) mice fed
      an atherogenic diet for 8 weeks. Bezafibrate decreased plasma levels of both
      cholesterol and triglycerides (TG), while increasing plasma levels of high
      density lipoprotein-cholesterol (HDL-C). Since hepatic TG production was
      significantly reduced in the bezafibrate-treated mice lacking LDLR, the plasma
      lipid-lowering effects of bezafibrate might be primarily mediated by the
      suppression of hepatic production of apolipoprotein-B-containing lipoproteins. In
      parallel with the reduced ratio of non-HDL-C to HDL-C, bezafibrate suppressed
      fatty streak lesions in the aortic sinus by 51%. To determine whether or not
      bezafibrate directly alters the expression of genes relevant to atherosclerosis,
      we measured mRNA expression levels of three genes in the aorta by real-time PCR:
      ATP-binding cassette transporter A1, lipoprotein lipase, and monocyte
      chemoattractant protein-1. The results showed that there were no differences in
      the expression of these genes between mice treated with bezafibrate and those
      not. In conclusion, bezafibrate inhibits atherosclerosis in LDLR-/- mice
      primarily by decreasing the ratio of non-HDL-C to HDL-C.

PMID- 18712056
TI  - Antioxidant treatment with alpha-tocopherol improves erectile function in
      hypertensive rats.
AB  - There is no known treatment for erectile dysfunction (ED) in hypertensive
      patients. We tested whether or not antioxidative therapy improves ED in the
      setting of hypertension. Spontaneously hypertensive rats (SHRs) were treated with
      a control chow or an alpha-tocopherol-enriched chow (12 or 24 mg/100 g chow) for
      8 weeks. The isometric tension of corpus cavernosum strips from these SHRs was
      recorded. nNOS and HO-2 gene expression and NOx, cGMP, thiobarbituric acid
      reacting substance (TBARS), and superoxide dismutase (SOD) activity levels were
      determined in serum and tissue. Relaxation in response to electrical field
      stimulation (EFS) in the corpus cavernosum increased after the administration of
      alpha-tocopherol at a dose of 24 mg/100 g chow. This effect was inhibited by a
      nitric oxide synthase (NOS) inhibitor and by a heme oxygenase (HO) inhibitor,
      nNOS and HO-2 gene expression and NOx concentrations in the corpus cavernosum
      were similar between 24 mg alpha-tocopherol-fed SHRs and controls. Tissue cGMP
      levels were greater in alpha-tocopherol-fed SHRs than in controls. Treatment with
      24 mg alpha-tocopherol decreased TBARS levels and increased SOD activity in the
      serum and corpus cavernosum. Relaxation in response to acetylcholine chloride in
      the corpus cavernosum was improved with alpha-tocopherol treatment at each dose.
      These results suggest that alpha-tocopherol treatment increases the diminished
      relaxation in the corpus cavernosum of SHRs by improving neuronal or endothelial
      function related to nitric oxide and carbon monoxide. This, in turn, indicates
      that antioxidant therapy may play a role in treatment for ED in hypertensive
      patients.

PMID- 18712057
TI  - Methylenetetrahydrofolate reductase C677T and glutathione S-transferase P1 A313G
      are associated with a reduced risk of preeclampsia in Maya-Mestizo women.
AB  - Preeclampsia, a common complication of pregnancy, is characterized by elevated
      blood pressure and proteinuria developing after 20 weeks' gestational age.
      Susceptibility to this syndrome is believed to have a genetic component. The aim
      of this study was to investigate whether or not the 5,10
      methylenetetrahydrofolate reductase (MTHFR) C677T and glutathione S-transferase
      P1 (GSTP1) A313G polymorphisms are associated with preeclampsia in Maya-Mestizo
      women. A case-control study was performed, in which 125 preeclamptic patients and
      274 healthy controls were genotyped for the MTHFR C677T and GSTP1 A313G
      polymorphisms by real-time PCR allelic discrimination. Allele and genotype
      frequencies were compared using the chi2 tests. The MTHFR 677T allele and the
      677TT genotype were significantly more frequent in the controls, suggesting an
      association with a decreased risk of preeclampsia (p = 0.017 and p = 0.007,
      respectively). Similarly, GSTP1 313GG/GC genotypes and the G allele were more
      frequent in controls, showing a significant association with reduced risk of
      preeclampsia (p = 0.008 and p = 0.013, respectively). Our results suggest, for
      the first time, that the MTHFR 677T and GSTP1 313G polymorphisms confer a
      significantly decreased risk of developing preeclampsia in the Mexican Maya
      Mestizo population.

PMID- 18712058
TI  - Cardiovascular remodeling and metabolic abnormalities in SHRSP.Z-Lepr(fa)/IzmDmcr
      rats as a new model of metabolic syndrome.
AB  - The purpose of this study was to evaluate whether the spontaneously hypertensive
      rat SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP fatty) is a useful animal model to clarify
      molecular mechanisms that underlie metabolic syndrome. We investigated
      histopathologic changes in the cardiovascular organs and metabolic
      characteristics of SHRSP fatty rats, which are congenic rats from a cross between
      SHRSP and Zucker fatty (ZF) rats. The aortic wall and cardiac, carotid, and renal
      arteries from SHRSP and SHRSP fatty rats were thicker than those of ZF rats. The
      renal cortex in SHRSP and SHRSP fatty rats showed severe glomerulosclerosis.
      Pancreatic islands in SHRSP fatty and ZF rats showed marked hyperplasia. Steady
      state plasma glucose concentrations were higher in SHRSP fatty than in ZF rats.
      Non-fasting triglyceride levels in SHRSP fatty rats were higher than in ZF rats.
      DNA synthesis in cultured vascular smooth muscle cells (VSMCs) from SHRSP fatty
      and SHRSP rats was significantly higher than that in VSMCs from Wistar-Kyoto
      (WKY) or ZF rats. Levels of platelet-derived growth factor A-chain and
      transforming growth factor-beta1 mRNAs were higher in VSMCs from SHRSP fatty and
      SHRSP than from ZF rats. Microarray analysis identified five genes that were
      significantly upregulated and four genes that were significantly downregulated in
      visceral adipose tissue of SHRSP fatty rats compared with levels in control
      strains (SHRSP and ZF rats). These findings suggest that the combination of
      hypertension and obesity accelerates vascular remodeling, dyslipidemia, and
      insulin resistance in metabolic syndrome. The phenotype of SHRSP fatty is similar
      to that of human metabolic syndrome, and therefore, studies of these rats may
      help clarify the molecular mechanisms that underlie metabolic syndrome in humans.

PMID- 18712059
TI  - Acute hyperglycemia and hyperinsulinemia enhance adrenergic vasoconstriction and
      decrease calcitonin gene-related peptide-containing nerve-mediated vasodilation
      in pithed rats.
AB  - Recent clinical studies have demonstrated that transient postprandial
      hyperglycemia and hyperinsulinemia may contribute to the development of
      hypertension. Therefore, we investigated the influence of acute hyperglycemia
      and/or hyperinsulinemia induced by glucose or insulin infusion on neuronal and
      humoral control of vascular tone in rats. Euglycemic male Wistar rats were pithed
      under anesthesia and arterial blood pressure was measured. Changes in vascular
      responses to spinal cord stimulation (SCS) and intravenous bolus injections of
      noradrenaline, angiotensin II, calcitonin gene-related peptide (CGRP),
      acetylcholine and sodium nitroprusside (SNP) were studied by infusing various
      concentrations of glucose or insulin. Continuous glucose infusion, which
      increased both blood glucose and serum insulin levels, significantly augmented
      adrenergic nerve-mediated pressor responses to SCS without affecting pressor
      responses to injection of noradrenaline or angiotensin II. In pithed rats with
      artificially increased blood pressure and blockade of autonomic outflow, glucose
      infusion attenuated CGRPergic nerve-depressor responses to SCS without affecting
      depressor responses to injection of CGRP, acetylcholine or SNP. In pithed rats
      treated with octreotide, which increased blood glucose without increasing serum
      insulin levels, glucose infusion caused only significant augmentation of
      adrenergic nerve-mediated pressor responses. Combined infusion of insulin and
      glucose, which resulted in increased serum insulin levels with euglycemia,
      significantly augmented adrenergic nerve-mediated pressor responses and
      attenuated CGRPergic nerve-mediated depressor responses. The present results
      suggest that acute hyperglycemia and hyperinsulinemia increase adrenergic nerve
      mediated vasoconstriction, which in turn blunts CGRPergic nerve function, and
      that the increase in plasma insulin concentration associated with hyperglycemia
      may be responsible for the alteration of neuronal vascular regulation.

PMID- 18712060
TI  - Attenuated increases in blood pressure by dynamic resistance exercise in middle
      aged men.
AB  - The present study was performed to test the hypothesis that the blood pressure
      (BP) response to resistance exercise in middle-aged men with stiffening arteries
      is greater than that in young men with compliant arteries. The BP responses to
      acute dynamic resistance exercise (leg press) at individual relative (low,
      moderate and high) and absolute intensities were investigated in both young and
      middle-aged men. A total of 21 sedentary healthy normotensive men, 21-25 years of
      age (young) and 41-59 years of age (middle-aged), were included in the study. At
      rest, the arterial compliance (simultaneous ultrasound and applanation tonometry)
      and muscle strength (leg press) were lower, and indices of arterial stiffness and
      BP were higher in the middle-aged men than in the young men (p < 0.05). There
      were no significant differences in height, body mass, or heart rate between the
      two groups. During exercise, the systolic BP of the middle-aged men at 80% one
      repetition maximum (1RM) was significantly lower than that of the young men for
      the last half of the exercise period (p < 0.05). The amounts of change in
      systolic and diastolic BP from baseline to the end of resistance exercise were
      lower in the middle-aged men than in the young men at individual relative
      intensities (p < 0.05) and at individual absolute intensity. In contrast to our
      hypothesis, these findings indicated that the BP response during dynamic
      resistance exercise using large muscle groups may be attenuated in middle-aged
      men relative to young men.

PMID- 18712061
TI  - [Research activities and their funding at universities ].

PMID- 18712062
TI  - [Mechanisms for induction of apoptosis in response to DNA damage].

PMID- 18712063
TI  - [p97ATPase-mediated biogenesis of the Golgi, ER and nuclear envelope].

PMID- 18712064
TI  - [Strong possibility of regenerative medicine by hair follicle stem cells].

PMID- 18712065
TI  - [Establishment and characterization of prion-infected microglial cells].

PMID- 18712066
TI  - [Evolution and functions of X-family DNA polymerases in eukaryotes].

PMID- 18712067
TI  - [Gene targeting in cultured human cells].

PMID- 18712068
TI  - [Physiological role of presynaptic Ca2+ channel complexes on neurotransmitter
      release].

PMID- 18712069
TI  - [Control of DNA replication: how to limit replication in a cell cycle].

PMID- 18712070
TI  - [Screening for novel enzymes: accessing the metagenome as an unexploited genetic
      resource].

PMID- 18712071
TI  - [Advantages and limitations of Triage DOA screening in clinical and forensic drug
      testing].

PMID- 18712072
TI  - [Aquatic biotoxins in relation to food poisonings].

PMID- 18712073
TI  - [Envenomation and poisoning caused by marine biotoxins in Okinawa].

PMID- 18712074
TI  - [Treatment of marine envenomation in the subtropical coral sea].

PMID- 18712075
TI  - [Case of serious renal failure induced by ingesting large volume of MAKIRON].
AB  - A 23-year-old male patient ingested 150 mL of MAKIRON in a suicide attempt and
      was transferred to the hospital emergency room approximately 30 hours after
      ingestion. Upon admission, components of MAKIRON, including naphazoline (1.4
      microg/mL), chlorpheniramine (0.81 microg/mL), dibucaine (3.2 microg/mL) and
      benzethonium (5.5 microg/mL) were detected in the patient's plasma. Direct
      hemoperfusion and hemodiafiltration enforcement were carried out and the chemical
      components of MAKIRON were not detected the following day. At the time of
      hospitalization, the patient presented with serious hepatopathy, pneumonia and
      acute renal failure. The hepatopathy and pneumonia resolved several days later;
      however, the patient required continuation of dialysis three times per week for
      seventeen days due to persistence of anuria. Few case reports on renal failure
      induced by MAKIRON have been published, whereas there are occasional reports of
      MAKIRON poisoning. Serious renal dysfunction in this case is thought to be due to
      both the large volume of MAKIRON ingested and the time delay between ingestion
      and treatment.

PMID- 18712077
TI  - [Devising a detector tube for allyl isothiocyanate].

PMID- 18712076
TI  - [Did the toxic drug that stayed in stomach of the patient break the nasogastric
      tube?; a case report].

PMID- 18712078
TI  - [One tablet of ESTARON-MOCHA contains 100 mg of caffeine].

PMID- 18712079
TI  - [Current topics and problems in toxicology laboratories--1--analysis of the
      poison causing elevated anion gap acidosis].

PMID- 18712080
TI  - [Department of Poison Laboratory, Niigata City General Hospital].

PMID- 18712081
TI  - [Section of Analytical Toxicology, Department of Clinical Laboratory, Kawasaki
      Medical School Hospital].

PMID- 18712082
TI  - [Study of acute poisoning at facilities for aged persons].

PMID- 18712083
TI  - [Noninvasive insulin delivery systems].
AB  - The review considers commercial insulin formulations. Special attention is paid
      to the difficulties and strategies of development of alternative hormone delivery
      systems (buccal, transdermal, intranasal, pulmonary and oral). At the moment
      there is only one approved formulation of the noninvasive insulin in the world.

PMID- 18712084
TI  - [Use of laws of interelement interactions for understanding of mechanisms of
      various human diseases].
AB  - The review considers the basic laws of interaction of elements in real
      physiological conditions of metabolism. The law of replacement and two it
      consequences have been formulated taking into account a major principle of
      cybernetics, the feedback principle. A rule of a fractional threshold and the law
      of toxicity based on the Mertz's rules have been formulated. These laws have been
      used here for consideration of mechanisms of occurrence and development of
      apoptosis and also side-effects of statins. Study of bioinorganic mechanisms of
      different diseases is a erspective way for search of complex connections of
      metals and ligands, capable to interaction with initiators of chain reactions,
      and for a finding of substances--inhibitors these reactions.

PMID- 18712085
TI  - [Changes in amino acid patterns of blood plasma in tumor patients treated with
      anticancer drug NSC-631570: possible approaches to cancer diagnostics].
AB  - In our early experimental (with W-256, SM-1 and PC-1 tumors) and clinical
      (breast, bladder and prostate cancers) studies the use of the anticancer drug NSC
      631570 was proven to be safe and highly effective, inhibiting protein synthesis
      in cancer cells, selectively accumulating in cancer tissue after a single
      intravenous administration and controlling cancer-induced metabolic imbalance.
      This drug inhibits metabolic processes in the tumor and causes metabolic
      disorders in cancer cells. Moreover, NSC-631570 induced the changes in certain
      amino acids concentrations in biological fluids and tumor tissue in animal models
      and cancer patients. These changes cannot be explained by metabolic amino acid
      disorders in cancer known so far. In this study the effects of NSC-631570 on
      blood plasma amino acids has been investigated. Blood was sampled from 10 healthy
      donors and 29 patients with different types of cancer (stomach, rectal, lung,
      breast, bladder, prostate, and leukemia). Comparison of NSC-531570 effects in
      plasma of healthy donors and cancer patients has shown, that this compoumd: 1)
      affects amino acids with positively charged (His, Arg) or not charged (Tyr, Thr,
      Gln) R-groups; 2) decreases concentration of His and increase the concentrations
      of beta-Ala and Tau. These changes depend on the concentration of NSC-631570 and
      the type of cancer. On the basis of the literature data and the results of our
      studies we suggest that Ukrain's biological actions in cancer are realized at
      least partly through selective interaction with amino acids, their derivatives,
      and plasma proteins. These data provide the background for the using Ukrain in
      the cancer detection and investigating the mechanisms of carcinogenesis.

PMID- 18712086
TI  - [Cholesterol lowering properties of a complex compound simvastatin with
      glycyrrhizic acid (simvaglyzin) in experimental models].
AB  - A molecular complex of simvastatin (SV) and glycyrrhyzic acid (GA) (at the ratio
      of 1 : 4), has been synthesized. The complex named "simvaglyzin" (SVG) was stable
      in aqeous and aqua-alcohol solutions at GA concentrations exceeding 0.2 mM. In
      vitro SVG acted as uncompetitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA
      reductase (Ki = 94 nM). Appearance of this inhibitory activity is associated with
      the cytochrome P450-dependent conversion of SVG. The addition of 1 mM methyrapone
      into incubation medium fully prevented the inhibition of 3-HMG-CoA reductase. SV
      and SVG (used at 300 nM concentration) inhibited mevalonate synthesis rate by
      39.15+/-8.27% and 38.85+/-3.04%, respectively. In vivo SVG showed dose-dependent
      cholesterol-lowering effect. In rats the cholesterol-lowering effect of SVG used
      at daily doses corresponding to 66 and 100 mg/kg of SV was equal to the effect of
      the daily dose 200 mg/kg of SV. The decreases of total cholesterol level in blood
      serum were 7%, 9% and 8%, respectively. Myotoxicity of those SVG doses estimated
      by creatine phosphokinase (CPK) activity in blood serum was lower than that of
      SV. In rats treated with SV the activity of CPK increased by 79% (p<0.01), while
      in SVG treated rats by 30% and 36% (p<0.05). Any increase of hepatotoxicity
      markers alanine aminotransferse or aspartate aminotransferase in blood serum was
      not observed. The data suggest pharmacological synergism attributed to the SV-GA
      complex formation and elevated safety of the resultant complex compared with the
      parent compound.

PMID- 18712087
TI  - [Determination of protease activity in blood and in microorganisms].
AB  - For determination of protease activity it is possible to use immunoglobulins.
      Since proteolytic products apparently do not retain substrate antigenic
      determinants, it is possible to use ELISA methodsfor monitoring for enzymatic
      process. ELISA determination of functional activity of specific IgA1-protease has
      been applied not only for detection of this enzyme, but also for measurement of
      its inhibition constants. Fixed on a micropanel IgG may be used for evaluation of
      total proteolytic activity. Depending on pH values, it is possible to measure
      activity of neutral, alkaline and acid proteases. This approach has allowed to
      estimate total proteolytic activity of neutral proteases of serum. Measurement of
      a total level of serum pepsinogene activity can have diagnostic importance in
      gastroenterology, due to decisive contribution of pepsinogen I to the measured
      activity.

PMID- 18712088
TI  - [LDL oxidation and uptake by monocyte-derived macrophages from blood of patients
      with ischemic heart disease].
AB  - The aim of this study was to test our hypothesis that monocyte-derived
      macrophages of patients with ischemic heart diseases (IHD, MPIHD) were
      prestimulated (primed) or stimulated cells whose capacity for LDL oxidation and
      uptake exceeded that ofmacrophages from healthy donors (MPN). Monocytes were
      obtained from the blood of 18 healthy donors and 25 IHD patients; plasma LDL-
      from 16 another group healthy donors (LDLN) and 15 patients with family
      hypercholesterolemia. Incubation of LDLN or LDLH with MPIHD or MPN was carried
      out under aerobic and hypoxic conditions. It was shown that incubation of LDLN or
      LDLH with MPIHD TBARS accumulation, LDL aggregation, apoB fragmentation were
      observed earlier and proceeded more actively than in the case of incubation with
      MPN. MPIHD (compared to MPN) more actively uptook LDLH and LDLN as accumulated
      greater amounts of total cholesterol (TCh) (by a factor of 1.8-2.1; p < 0.05
      0.01), and their viability decreased to a markedly greater degree (p < 0.01).
      MPIHD and MPN also oxidized and took up LDLH with a higher intensity than LDLN,
      and their capacity for LDL oxidation and uptake increased, under hypoxic
      condition, compared to those under aerobic conditions. Thus, new experimental
      results provide direct evidence that macrophages of IHD patients are in vivo
      priming or stimulated cells and that this stimulation, especially in combination
      with hypercholesterolemic LDL and hypoxia, is a very strong risk factor that can
      predispose these patients to the onset or progression of atherosclerosis. Using
      MPIHD, it was created express-method for evaluation the degree of
      monocyte/macrophage stimulation in patients with IHD, selection of premedication
      medicine and new antiatherosclerotic and antiischemic drugs.

PMID- 18712089
TI  - [Effects of (22S,23S)- and (22R,23R)-3beta-hydroxy-22,23-oxido-5alpha-ergost
      8(14)-en-15-ones on cholesteryl esters biosynthesis and acyl-CoA:cholesterol acyl
      transferase activity in Hep G2 cells].
AB  - Novel synthetic oxysterols (22S,23S)-3beta-hydroxy-22,23-oxido-5alpha-ergost
      8(14)-en-15-one (I) and (22R,23R)-3beta-hydroxy-22,23-oxido-5alpha-ergost-8(14)
      en-15-one (II) influenced cholesteryl esters biosynthesis in human hepatoma Hep
      G2 cell line from [14C]acetate (85% and 180% compared to control at the
      concentrations of 5 microM). The level of cholesteryl esters biosynthesis in Hep
      G2 cells from [14C]oleate increased in the presence of ketosterol (I) in a dose
      dependent manner, whereas the level of cholesteryl esters biosynthesis in the
      presence of ketosterol (II) reached the maximal value (269+/-20% from control) at
      the concentration of 1 microM. In a cell free system ketosterol (I) increased the
      rate of ACAT-dependent cholesterol acylation like 25-hydroxycholesterol, however,
      ketosterol (II), efficiently stimulating initial rate of ACAT-catalyzed
      cholesterol esterification, caused in rapid inactivation of this enzyme.

PMID- 18712090
TI  - [Molecular characteristics of testosterone binding globulin and analysis of their
      regulation].
AB  - Molecular characteristics of testosterone binding globulin (TeBG) were
      investigated in microaliquots of human serum samples using 3H-5-alpha
      dihydrotestosterone radioligand assays. Under experimental conditions used TeBG
      demonstrated high conformational plasticity and ability to adopt three
      conformational states (olygo-, di-, and monomer) with different functional
      activities. Using alipidspolyene complex from basidiomycete Laetiporus sulphureus
      we demonstrate a novel effective pharmacological correction of the TeBG
      characteristics.

PMID- 18712091
TI  - [Variations in glycoprotein IIb-IIIa (alphaIIb/beta3-integrin) content in healthy
      donors. Influence on platelet aggregation activity and efficacy of aspirin
      action].
AB  - Effects of fibrinogen receptor, glycoprotein (GP) IIb-IIIa (alphaII/(beta3
      integrin) content, GP IIIa genetic polymorphism (substitution Leu33Pro) and
      fibrinogen concentration in blood plasma on platelet aggregation activity were
      studied in a group of healthy volunteers. The GP IIb-IIIa content on platelet
      surface in 35 tested donors varied (40-71) x 10(3) per platelet. Repeated
      measurements revealed that the GP IIb-IIIa content coefficient of variation was
      9.5%, and deviations from mean levels did not exceed 20%. The level and rate of
      platelet aggregation induced by ADP (1.25-20 M) correlated with GP IIb-IIIa
      number (r from 0.315 to 0.591) and were higher in a group of donors with high in
      comparison with low GP IIb-IIIa content (> 60 and (40-50) x 10(3) per platelet
      respectively). Aspirin, the inhibitor of thromboxane A2 synthesis, partially
      suppressed ADP-induced platelet aggregation. The level of residual aggregation in
      the presence of aspirin also correlated with GP IIb-IIIa content and increased in
      subjects with high receptor content. Parameters of ADP-induced aggregation did
      not differ in donors with GP IIIa Pro33(-) (Leu33Leu33, n = 20) and Pro33(+)
      (Leu33Pro33, n = 13, and Pro33Pro33, n = 2) genotype. GP IIb-IIIa content was
      also not affected by GP IIIa polymorphism. No significant correlations were found
      between the level and rate of platelet aggregation and fibrinogen concentration
      in blood plasma. The data obtained indicate that effects of GP IIb-IIIa
      variations in content on platelet aggregation are higher than GP IIIa Leu33Pro
      polymorphism and variations of fibrinogen concentration. High GP IIb-IIIa content
      is associated with increased platelet aggregation activity and decreased efficacy
      of aggregation inhibition by aspirin.

PMID- 18712092
TI  - [Early and late biomarkers of late myocardium necrosis in patients with acute
      coronary syndrome].
AB  - Cardio-vascular diseases and acute coronary syndrome (ACS) in the first place
      play the first role in the structure of diseases and mortality of world
      population. Effective method of diagnostics of ACS consists in detecting early
      and late biomarkers of myocardium necrosis. The article presents characteristics
      of such biomarkers indices as myoglobin, cardiotroponins, MB-fractions of
      creatine phosphokinase, cardio-form of protein, lactate dehydrogenase, aspartate
      aminotransferase. The authors described in the artcile diseases which are
      accomponied with increase in the level of cardiotroponins.

PMID- 18712093
TI  - [Changes of electrocardiography parameters in patients with bronchial asthma and
      arterial hypertention].
AB  - The authors presents in the article based on observations of 89 patients
      questions related to the changes of intracardial hemodynamics in patients with
      bronchial asthma and arterial hypertention (AH) observed using echocardiography.
      Disorders of indices of intracardial hemodynamics in patients with bronchial
      asthma and arterial hypertention have more evident negative tendency than that in
      patients with isolated bronchial asthma (BA) or arterial hypertention. It was
      established that such patients (without taking into consideration the degree of
      severity of BA) have considerably an increased volume indices of left and right
      ventricule, increased pressure in the lung artery, right ventricule hypertrophy,
      left ventricule concentric hypertrophy as well as disorders of diastolic heart
      function of relaxation type. Comparing indices of intracardial hemodynamics
      depending on the degree of severity of BA it was found that progression of lung
      hypertension, disorders of diastolic and systolic heart functions correlates with
      the degree of severity of BA. It leads to earlier formation of biventricular
      heart failure.

PMID- 18712094
TI  - [Thrombocytopenia in patients with systemic lupus erythematosis as a risk factor
      for thrombotic complications and its connection with severity and the course of
      the disease, systemic lupus erythematosis].
AB  - Thrombocytopenia prevalance and its association with antiphospholipid syndrome,
      disorders of the hemostasis system, the course and activity of the disease have
      been studied in SLE patients. 10.5% of 457 SLE patients in central and western
      part of Ukraine had thrombocytopenia which non-significantly depended on sex, age
      and disease duration but was tightly associated with cardiovascular disorders.
      Thrombocytopenia appears as an independent risk factor for vascular disorders
      which does not depend on lipid metabolic disorders and system inflammatory
      reaction but is firmly associated with the presence of antiphospholipid syndrome,
      beta-2-glycoprotein I levels, thrombocyte hyperactivity, antithrombin III and
      tissue plasminogen activator deficiency.

PMID- 18712095
TI  - [Peculiarity of cell energy metabolism in newborns with hypoxic-ischemic
      encephalopathy caused by asphyxia].
AB  - The authors have studied changes of activity of succinate dehydrogenase (SD) of
      peripheral blood lymphocytes of newborn with hypoxic-ischemic encephalopathy at
      early neonatal period and against cerebrokurin medicine administration. Newborn
      children with hypoxic-ischemic encephalopathy due to severe asphyxia have
      significant disturbancies of cyto-energy metabolism which is proved through
      decrease in activity index of SD and decrease in quantity of the cells with
      moderate and high activity. Lymphocytes of newborns with severe asphyxia were
      caracterized on six days by absence of the cells with moderate and high activity.
      Newborns with severe asphyxia who had been prescribed cerebrokurin had on their
      six days considerable increase in lymphocytes with moderate and high activity.

PMID- 18712096
TI  - [Module of hypercoagulation as a biomarker for estimation of hemostasis risk
      factor of thrombosis, determination of an individual antiaggregant dose and the
      way of its use in patients with arterial hypertension].
AB  - 12 patients with stage II arterial hypertantion have been administered a complex
      therapy including antihypertensive, hypocholesterolemic (statines), and
      antiagregant (aspirin, acelisin) agents as a preventive maintenance of vascular
      complications (stroke, myocardial infarction). Optimization of individual
      treatment was established by controlling parameters of the integrated indicator
      of the coagulation cascade of whole blood. This indicator is called the
      coagulation module (CM). In a clinical practice this biomarker favours
      qualitative assessment of disorders of the coagulation potential and degree of
      its dysfunction. Patients having a high risk factor (CM+VI-VIII degree) have
      began their treatment with intramuscular administration of acelisin in individual
      doses within 4-6 days.

PMID- 18712097
TI  - [Modern aspects of diagnostic and treatment of Barretts esophagus].
AB  - In this paper the modern aspects of diagnostic, treatment and management of
      Barretts esophagus are presented. It has concluded that the most effective
      strategy for management of Barretts esophagus is long-term use of modern PPI,
      endoscopical and histological control.

PMID- 18712098
TI  - [Diagnostics of lung contusion in patients with thoracic closed injury and
      prophylaxis of complications].
AB  - Among 304 patients hospitalised with thorax closed injury 205 patients had lung
      contusion. The use of a complex diagnostics allowed to discharge 176 patients
      without any complications. The development of complections was observed in 128
      patients, which occurred after the patients had had their injuries. Application
      of endoscopic sanation and treatment allowed to discharge patients in early
      terms.

PMID- 18712099
TI  - [Etiology of infectious diseases in pregnant women with symptoms of fever and
      lung syndrome].
AB  - 31 samples of blood serum of pregnant women with acute respiratory virus
      infection and pneumonia symptoms who had been administered into hospital were
      analyzed. Antibacterial and antifungal treatment was ineffective. Autumn-winter
      spring seasonality was detected. In connection with above-mentioned, an attempt
      was made to find out the etiology of a disease using viroloy methods. Primers of
      hantaviruses, Crimea-and-Congo hemorrhage fever, coronaviruses, SARS,
      Leptospirosis and virus hepatitis. Genome of B hepatitis virus was discovered in
      3 samples, C--in one sample, G--in four samples. The test for other primers was
      negative. It was shown that in case of serious clinical course only abortion can
      save mother's life. It is necessary to find out aetiology of the disease, primers
      and other pathogenic organisms of virus infections.

PMID- 18712100
TI  - [Apoptosis and pathological process].
AB  - Apoptosis (programmed cell death) occurs normally for maitenance of tissue
      homeostasis and play an important role in morphogenesis, embriogenesis and tissue
      growth. On the other hand, apoptosis may be involved in different pathological
      processes such as malignancy, infectious diseases and autoimmune disorders.
      Apoptosis is regulated by various mediators. Caspases, death receptors,
      mitochondria, Bcl-2 protoncogenes and tumor supressor genes are considered to be
      the most important of them. Advance in apoptosis regulation research suggests
      enormouse facilities for therapy of wide range of human illnesses.

PMID- 18712101
TI  - [Thrombosis of the portal vein].
AB  - Thrombosis of the portal vein is relatively rare disease which presents some
      difficulties to diagnose in patients with it. It is discussed in the article the
      case of thrombosis of the portal vein diagnosed after the patient's death.

PMID- 18712102
TI  - [Role and place of military medical service in Ukraine in the state service of
      medicine of catastrophes].
AB  - The authors discusses in the article important questions related to providing
      medical care during emergency situations. Promising directions on creation of
      unique state medicine service of catastrophes and generalized plan of interaction
      of medical components refering to different ministries and institutions of the
      country were proposed by the authors. The role and place of medical care of
      military army of ukraine in state service of medicine of catastrophes were shown
      in the article.

PMID- 18712103
TI  - [Legal regulation of participation of medical personnel in the international
      peacemaking action: genesis and trends of the development].
AB  - The article is devoted to the question on legal regulation of participation of
      medical personnel in an international peacemaking action.

PMID- 18712104
TI  - [Dynamics of morbidity indices in military personnel during their adaptation to
      military service].
AB  - The authors studied changes of morbidity indices of military personnel of armed
      forces of Ukraine during their adaptation to military service. 1200 military
      personnel (ranks and sergeants) from different units of Kiev garrison were
      distributed into three identical groups. Conditions of military service for the
      first group were the most favourable, for the second group--standard, for the
      third group--the most complicated. The results of the study showed that in the
      process of adaptation to military service, morbidity indices of military
      personnel increase, period of changes of these indices coincide with the stages
      of adaptation process. The degree of increase of morbidity indices depends on
      complexity of military service.

PMID- 18712105
TI  - [Diseases and causes of death of outstanding creative and scientific figures of
      XVII-XX centuries].
AB  - The article reviewed the literature which analyzes clinical symptoms and causes
      of some creative and scientific figures of XVII-XX centuries. A conclusion has
      been made that there are not enough works with professional retrospective
      investigation of somatic diseases and causes of death of ukrainain outstanding
      cultural and scientific people in today's national medical literature.

PMID- 18712106
TI  - [Furin and its biological role].
AB  - The survey deals with structure, properties and biological role of furin, the
      calcium-dependent serine endoprotease, which is expressed in all tissues and cell
      lines examined. It is the best-characterized representative of the mammalian
      subtilisin-like family of proprotein convertases, which is capable to cleave
      precursors of a wide variety of proteins, including hormones, growth factors,
      serum proteins, proteases of the blood-clotting system, matrix
      metalloproteinases, receptors, viral envelope glycoproteins, and bacterial
      exotoxins, and so on. The enzyme plays the essential role in embryogenesis,
      homeostasis; it is also involved in tumor metastasis, activation and virulence of
      many bacterial and viral pathogens and in neurodegenerative processes associated
      with Alzheimer's disease. Furin is a very specific enzyme: it recognizes the
      cleavage-site sequence Arg-Xaa-Lys/Arg-Arg and catalyzes the hydrolysis of the
      precursors, containing a pair of basic amino acids Arg-Arg or Lys-Arg. The enzyme
      is a multidomain protein which is initially synthesized as 100 kDa glycosylated
      profurin consisting of 794 amino acid residues (for human furin) and including a
      N-terminal signal peptide, propeptide, catalytic domain, possessing approximately
      30% homology to subtilisin, a well-conserved P-domain, Cys-rich domain,
      transmembrane domain and cytoplasmic domain. The active site cleft of furin
      differs considerably from that of subtilisin with respect to the depth, shape and
      molecule charge. In furin it is a canyon-like groove with clusters of negatively
      charged residues along it. Furin inhibitors are rather promising therapeutic
      agents for treating furin-mediated diseases and bacterial infections. Most furin
      inhibitors belong to proteins or peptides. The protein-based inhibitors include
      both naturally occurring and bioengineered variants of protease inhibitors. The
      peptide-based inhibitors are represented by polyarginines, peptidyl chloromethyl
      ketones, aminomethyl ketones or ketomethylene pseudopeptides, isostere-containing
      cyclic peptides, short peptides derived from the prosegments of furin or al-PDX
      related peptides. The nonpeptide inhibitors are natural products of the
      andrographolide family, certain metal complexes of pyridine derivatives and small
      molecules derived from 2.5-dideoxystreptamine. The furin inhibitors may be used
      not only as valuable tools for studying furin action, but also as therapeutic
      agents for furin-dependent diseases.

PMID- 18712107
TI  - [Polyamines and collagenes interaction in different processes of extracellular
      matrix production and functioning in norm and with pathology].
AB  - A great file of experimental data on tight interrelations between polyamines and
      main components of extracellular matrix (collagenes, laminin, fibronectin, etc.)
      metabolisms has been accumulated in the recent twenty years. Consequences of such
      tight interaction of collagenes, polyamines, enzymes of their metabolisms during
      formation and functioning of extracellular matrix are realised not only at a
      cellular level (proliferation, differentiation, adhesion, apoptosis), but also at
      the level of the whole organism (immunity, connective tissues and skeleton
      formation, tumors). Search for the ways of cells behavior modulation via
      influence on the levels of polyamines and contents of extracellular matrix at
      present is new direction in pharmacology of antitumor preparations that enables
      regulation of organism-tumor relationships, inhibition of angiogenesis, tumor
      growth and metastasing.

PMID- 18712108
TI  - [Calix[4]arene methylenebisphosphonic acids: the features of alkaline
      phosphatases inhibition].
AB  - The inhibition of alkaline phosphatases by calix[4]arenes functionalysed at the
      macrocyclic upper rim by one or two methylenebisphosphonic acid fragments has
      been investigated. It is established, that calix[4]arene
      bismethylenebisphosphonic acid displayed stronger inhibition of alkaline
      phosphatase from bovine intestine mucosa than calix[4]arene
      methylenebisphosphonic acid. At the same time, the both inhibitors showed almost
      similar levels of inhibitory activities in respect of bovine kidney alkaline
      phosphatase or E. coli alkaline phosphatase. The tested compounds were docked
      computationally to the active site of the E. coli alkaline phosphatase. On the
      basis of results obtained the possible binding modes of inhibitors were analysed.

PMID- 18712109
TI  - [Investigation of Ca2+ -induced changes of membrane potential of smooth muscle
      mitochondria using flow cytometric analysis].
AB  - Using flow cytometric analysis and potential-sensitive fluorescent dye TMRM Ca2+ 
      induced changes of membrane potential of isolated smooth muscle mitochondria were
      studied. It was shown, that Ca2+ (100 microM) addition to the incubation medium
      induced mitochondrial membrane depolarization that probably could be explained by
      Ca2+/H+ -exchanger activation which functioning lead to membrane potential
      dissipation. In the case of ruthenium red (10 microM) preliminary presence in
      incubation medium, Ca2+ (100 microM) addition did not lead to membrane potential
      dissipation. Hence, membrane potential dissipation was caused by an increase of
      matrix Ca2+ concentration. In the presence of Mg2+ (3 mM) and ATP (3 mM), Ca2+
      addition did not cause depolarization. It was supposed that in this case ATP
      synthase acted in the opposite direction as H+ -pump and prevented from
      mitochondrial membrane potential dissipation. Thus, the flow cytometry method
      allows to register membrane potential of isolated smooth muscle mitochondria and
      also to test the effectors, capable to modulate this parameter.

PMID- 18712110
TI  - [Inactivation of AMP-deaminase from white muscle of Cyprinus carpio in the
      systems with free radical oxidation].
AB  - The purification and in vitro inactivation of AMP-deaminase from white muscle of
      carp Cyprinus carpio were conducted in the Fe2+/H2O2 and Fe2+/ascorbate oxidation
      systems. The enzyme activity decreases by 50% within 30 minutes of incubation in
      the presence of 100 microM of hydrogen peroxide and 5 microM of ferrous sulfate.
      Inactivation depended on incubation time and concentrations of FeSO4 and H2O2. In
      the system Fe2+/ascorbate the enzyme activity decreased by 50% at concentration
      of ascorbate 1 mM and 5 ferrous sulfate microM. Sodium nitrite did not affect the
      activity. S(0.5) and n(H) of both native and partially inactivated enzymes were
      virtually the same, while maximal activity of the inactivated enzyme was 2-3-fold
      lower than that of the native one.

PMID- 18712111
TI  - [pH-dependence of inhibitory action of eosin Y on ATPase activity of smooth
      muscle actomyosin complex of the uterus].
AB  - Research of pH-dependence of inhibitory action of eosin Y (2',4',5',7'
      tetrabromofluorescin) on ATPase of contractile proteins of smooth muscles of the
      uterus has shown that the increase of concentration of this inhibitor (from 0.1
      to 10 microM) influenced the profile of pH-dependence of ATPase activity of
      actomyosin: in the presence of 0.1 microM eosin Y the change of optimal value of
      pH has been observed in more sour side in relation to the control; at the
      increase of concentration of eosin Y (from 0.5 to 10 microM) the strongly
      pronounced optimum of pH is absents in general. The ability of eosin Y to inhibit
      the ATPase activity of contractile complex is dependent on pH of incubation
      environment. The change of pH from 6.0 to 7.2 results in a 9-fold decrease of
      magnitude of apparent constant of inhibition Ki (from 6.5 +/- 0.8 microM to 0.74
      +/- 0.07 microM). The obtained results indicate that the diminishing of
      concentration of H+ in an incubation environment favors the increase of affinity
      ATPase of actomyosin for eosin Y and prove the important role of ionization
      processes in the system "enzyme-substrate-inhibitor" for realization of
      inhibitory action of eosin Y.

PMID- 18712112
TI  - [The N-stearoylethanolamine effect on the NO-synthase way of nitrogen oxide
      formation and phospholipid composition of erythrocyte membranes in rats with
      streptozotocine diabetes].
AB  - The influence of N-stearoylethanolamine (NSE) on the NO-synthase way of NO
      generation and phospholipids composition of erythrocyte membranes of rats with
      streptozotocine-induced diabetes has been studied. It has been shown that the
      activation of iNOS activity, cNOS activity inhibition and increase of the stable
      NO metabolites content takes place in the red blood cells (RBC) of diabetic rats.
      The alterations were also found in the RBC membrane phospholipid content: a
      decrease of phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol,
      sphingomieline content and increase of phosphatidylethanolamine,
      phosphatidylcholine lysoforms level. The NSE suspension administration (50 mg/kg
      of body weight) to diabetic rats (3 months after the diabetes induction) resulted
      in iNOS activity inhibition, recovering of cNOS activity and normalization of NO
      stable metabolites level in RBC. The decrease of phospholipids lysoform levels,
      normalization of phosphatidylethanolamine, phosphatidylcholine content and
      increase of phosphatidylinositol level were found after NSE action.

PMID- 18712113
TI  - [Process of platelets activation by streptokinase].
AB  - This study concerns the influence of streptokinase and antistreptokinase
      antibodies on rabbits platelets in blood plasma depleted of plasminogen. The
      immune complex streptokinase-antibody causes platelets activation, whereas other
      investigated immune complexes didnot express such activity. Platelets aggregation
      wasnot detected in any case. It was determined that streptokinase induces
      platelets activation in the rabbit plasma with high titre of antistreptokinase
      antibodies in absence of plasminogen.

PMID- 18712114
TI  - [Modifying effect of low-molecular metabolities on the state of extracellular
      matrix of connective tissue of animals].
AB  - On the basis of complex approach to bone and haematopoetic tissue interaction the
      authors studied the influence of low weight metabolites on stromal fibroblasts
      and components of extacellular matrix of bone and skin (collagen and
      glycosaminoglycans). Specificity of different metabolites action on physico
      chemical abilities of type I collagen, amino acid composition changes, surface
      charge, ratio of alpha- and beta-compounds, BrCN-fragments of alpha-1 component
      cross-links was shown. The dose dependence of formiate effect on processes of
      proteins glycosilation, cross-linking in bone and cartilage connective tissue and
      serum glycoproteins was established. The results obtained showed sensitivity of
      the bone tissue exstacellular matrix to influence of low-weight metabolites
      action at the level of post-synthetic modification of its components, their
      intermolecular interaction and process of osteogenesis.

PMID- 18712115
TI  - [Age peculiarities in changes of free radical oxidation processes in the brain of
      rats with hypothyroidism].
AB  - The objective of the present experiment was to study age peculiarities of free
      radical protein oxidation and lipid peroxidation in brain of 1.5-month-old and 12
      month-old rats with drug-induced hypothyroidism. It has been shown that
      hypothyroidism in both 1.5-month and 12-month old rat is accompanied by the
      oxidative stress in the brain. It manifests by an increase of content of lipid
      peroxidation products and protein carbonyls in mitochondrial and microsomal
      fractions. Hypothyroidism decreases the prooxidant effect of exercises on the
      brain mitochondria.

PMID- 18712116
TI  - [Influence of omeprasole and lansoprasole on Na+, K+ -ATPase and Mg2+ -ATPase
      activity of the plasmatic membrane of myometrium smooth muscle cells].
AB  - The paper deals with the influence of the proton pump inhibitors - omeprasole and
      lansoprasole on the enzymatic activity of the ouabain-sensitive Na+, K+ -ATPase
      and the ouabain-resistant Mg2+ - ATPase in the suspension of the myometrium cell
      plasmatic membranes treated with 0.1% digitonin solution. It was found, that
      omeprasole and lansoprasole inhibited Na+, K+ -ATPase in the range from 10 to 100
      microM. The maximal effect was observed at a concentration of 100 microM with the
      percentage of inhibition of 81 and 86% at an average as compared with the control
      for omeprasole and lansoprasole, respectively. The magnitudes of the inhibition
      coefficient I(0.5) for omeprasole and lansoprasole were 35.60 +/- 0.81 and 29.40
      +/- 1.79 microM respectively. Meanwhile cooperative effects on the Na+, K+ -
      ATPase activity were not found, as the Hill coefficient n(H) for omeprasole was
      1.00 +/- 0.08, while for lansoprasole it was 1.20 +/- 0.03. These substances had
      also insignificant influence on Mg2+ -ATPase: the enzymatic activity was
      decreased to 84 and 82% as compared with the control with omeprasole and
      lansoprasole, respectively, in concentration of 100 microM for each inhibitor.
      The inhibition of Na+, K+ -ATPase activity can evidence for the possible side
      effects of omeprasole and lansoprasole when they are used for treatment of acid
      dependent diseases of the stomach. In addition, obtained experimental data can be
      useful for further research of the membrane mechanisms of omeprasole and
      lansoprasole action on cationic exchange in the smooth muscle cells.

PMID- 18712117
TI  - [Influence of vitamin E application period on the mineral and D-vitamin
      metabolism in the organism].
AB  - It was shown, that influence of vitamin E on mineral and D-vitamin metabolism
      depends on its doses and application period: physiological doses of vitamin E
      activate and large doses - inhibit the effect of vitamin D3 in regulation of
      mineral metabolism in the organism. The duration of application of large doses of
      vitamin E (higher than 20 physiological doses) during which the negative changes
      are not determined has not to exceed 10 days.

PMID- 18712118
TI  - [Influence of low dozes of ionizing radiation on accumulation of melanin pigments
      and catalase and superoxidedismutase activities in Cladosporium cladosporioides].
AB  - Influence of low dozes of ionizing radiation on melanin pigments synthesis and
      activity of antioxidant enzymes catalase and superoxidedismutase of two strains
      of Cladosporium cladosporioides 4, (isolated from radioactive soil) and 396
      (control) were investigated. It was shown, that in C. cladosporioides 4 under the
      exposure of ionizing radiation an increase of melanin synthesis in a stationary
      growth phase and increase of superoxidedismutase activity in a logarithmic phase
      were observed; in the control strain C. cladosporioides 396 activation of melanin
      synthesis and superoxide dismutase activity in both growth phases was revealed.
      It was established that in C. cladosporioides 4 the endocellular catalase
      activity in a logarithmic phase is 3.2 times higher, than in control strain.
      Under the action of ionizing radiation a 2-fold increase of this enzyme activity
      unlike the control strain in which the activity inhibition was revealed. The
      obtained results testify to the complex response of antioxidant systems and
      melanin to the action of low dozes of radiation which depends on the growth phase
      and presence of radioadaptation properties in the investigated fungi.

PMID- 18712119
TI  - [New approach in the treatment of newborn calves' dyspepsia and its controlling
      by the analysis of phospholipids of blood].
AB  - It's known that in newborn calves with dyspepsia in lipids leucocytes,
      erythrocytes, plasma and serum extracted from blood occur violation of parity
      between separate classes phospholipids in compare with healthy calves. It's
      revealed increasing of lipophosphatidilholin, sphingomielin, phosphatidilholin
      and decreasing of amount of phosphatidilserin, lizophosphatidic and phosphatidic
      acids in quantitative contents of phospholipids extracted from blood components.
      Indicated violations could be recovered after the treatment of ill calves by
      enterosgel in doze, which we developed and tested.

PMID- 18712120
TI  - [Activity of peptidyl-dipeptidase A and carboxypeptidase N in the serum of
      patients with Alzheimer disease].
AB  - The activity of peptidyl-dipeptidase A and carboxypeptidase N taking part in
      peptide metabolism in the serum of patients with Alzheimer disease were studied.
      The role of these enzymes in the metabolism of neuropeptides and beta-amyloid at
      the Alzheimer disease was discussed.

PMID- 18712122
TI  - [Science of life: from molecules to molecular machines of vital activity
      processes].

PMID- 18712121
TI  - [Skvyrs'ka Etel Berkivna--a gifted researcher and pedagogue (to the 100th
      anniversary of birthday)].
AB  - E. B. Skvyrska was born in the town of Chigirin. In 1928 she graduated from the
      Agricultural-Pedagogical Division of the Kyiv Institute of People's Education
      (Taras Shevchenko Kyiv National University, now) in speciality pedagogue
      biologist. In 1937 she finished the post-graduate course at the Institute of
      Biochemistry of the Academy of Sciences of the Ukrainian SSR, in 1940 she
      defended the thesis for the Candidate's degree in biology and the title of the
      senior researcher was conferred on her in 1941. Beginning from 1936, E. B.
      Skvyrska had been working at the Institute of Biochemistry. She was working at
      the Department of Structure and Biochemistry of Nervous System (till 1963), and
      then at the Department of Structure and Biochemistry of Nuclear Acids (till
      1973). In 1958 she defended the thesis for the Doctor's degree. From 1938 to 1941
      E. B. Skvyrska worked as the assistant, and from 1945 to 1950 as the docent of
      the Department of Biochemistry at the Taras Shevchenko Kyiv (State) National
      University. Up to 1941 her scientific work was dedicated to the investigation of
      peculiarities of carbohydrate metabolism of the central and peripheral nervous
      system depending on the animal age. Since 1951 E. B. Skvyrska was investigating
      the metabolism of high-molecular phosphorus-including compounds (nucleic acids,
      phosphoproteins and phospholipids) in the central nervous system during the
      excitation and inhibition, in ontogenesis, in functionally and morphologically
      different parts of the nervous system, in different structure elements of the
      nerve cell. The results of investigations allowed finding the biochemical
      peculiarities connected with the difference of structure and function of
      morphologically different divisions of the nervous system. Peculiarities and
      functioning of t-RNA and aminoacyl-t-RNA synthetases of rats in norm and during
      starvation were studied at the Department of Nucleic Acids. More than 50
      scientific works have been published.

PMID- 18712123
TI  - [Do patients understand special terms in the product information?].
AB  - The product of information for drugs is essential for the determinant use of
      drugs to guarantee the efficacy and safety of drugs. Supposition is the
      comprehension of special terms. The interviews of 277 patients by chance with 433
      questionnaires (3313 questions) in the private practices showed that only a
      quarter of the special terms could be understood. Therefore it is necessary that
      the special terms must be translated to German or should be explained.

PMID- 18712124
TI  - [Comparison between laryngeal mask airway and bag valve mask].

PMID- 18712125
TI  - [Coxibes--bullying of a drug class?].

PMID- 18712126
TI  - [Importance of the spread of Methicillin-resistant Staphylococcus aureus (MRSA)
      in fattened pigs for humans?].

PMID- 18712127
TI  - [Sublingual immunotherapy (SLIT) in the allergologist's practice].

PMID- 18712128
TI  - [Tolerability and efficacy of a herbal combination preparation in children and
      adolescents with recurrent infections of the upper respiratory tract].

PMID- 18712129
TI  - [Differential medical care of functional dyspepsia].

PMID- 18712130
TI  - [Treatment of chronic osteoarthritis pain: effectivity and safety of a 7 day
      matrix patch with a low dose buprenorphine].
AB  - Patients with osteoarthritis often suffer from chronic pain. If pain treatment
      with NSAIDS and coxibes is no longer indicated, a constant and user friendly
      opioid analgesia can be achieved with a low dose buprenorphine patch being
      applicated using an interval of 7 days. The use of this matrix patch was
      evaluated in a multicenter observational study on 4263 patients in clinical
      practice. During treatment a significant decrease of mean pain intensity on a 11
      point scale could be observed from 6.9 points before using the patch to 2.9
      points at the end of observation. Further effects were a decrease of additional
      analgetic medication and an improvement of aspects of life quality, e.g. mobility
      and quality of sleep. Only in 4.5% of the patients adverse effects were observed,
      reflecting the expected range of adverse effects of opioids. Thus it could be
      demonstrated that the use of the transdermal patch is an effective, user friendly
      and safe way of chronic pain relief for osteoarthritis patients.

PMID- 18712131
TI  - Medical record keeping--are we prepared?

PMID- 18712132
TI  - A survey of obstetricians' practice of using prophylactic antibiotics in vaginal
      deliveries and caesarean sections.
AB  - Antibiotics are prescribed in pregnancy but only few reports provide information
      about the actual practice of prophylactic antibiotics usage in various
      obstetrical conditions amongst obstetricians. The present study evaluates the
      practice of obstetricians of Delhi regarding prescription of antibiotics in
      vaginal deliveries and caesarean sections. The open-ended predesigned
      questionnaire study incorporated details of the obstetricians working in
      different hospitals of Delhi and their practice of prescribing antibiotics in
      vaginal deliveries, episiotomies and caesarean sections was filled by
      obstetricians. The data was analysed using Student's 't' test and Chi-square
      test. The mean age of obstetricians was 35.5 years; 90% were females and 48.9%
      were postgraduate students with 70% less than 5 years experience and 77.8% were
      working in a government hospital. In episiotomy, 18.9% obstetricians did not use
      antibiotics while 33.3%, 27.8% and 20% obstetricians used ampicillin, amoxicillin
      and cephalexin orally for 5 days respectively. Injection cefazolin was used
      intravenously, 1 g 12 hourly for 3 days by 34.4% and 33.3% obstetricians in
      elective and emergency caesarean sections respectively, while it was used for 5
      days by 35.5% and 41.1% obstetricians respectively. A combination of ampicillin,
      gentamicin and metronidazole for 5 days was used by 30% and 25.5% obstetricians
      for elective and emergency caesarean sections respectively. In spite of clear
      evidence from Cochrane Database of Clinical Reviews that use of penicillin or
      first generation cephalosporins in single dose therapy is effective; the actual
      practice is contrary with use of multiagent antibiotics for long periods, being
      very rampant in actual clinical practice.

PMID- 18712133
TI  - A hospital-based study of splenomegaly with special reference to the group of
      indeterminate origin.
AB  - In any study there remains a proportion of cases, about 25-40%, where cause of
      splenomegaly is not identified on usual evaluation, that is labelled as
      indeterminate group. The aim of this study was to evaluate various causes of
      splenomegaly. Thereafter the patients with splenomegaly of indeterminate origin
      were to be re-evaluated with detailed investigations (for the cause of
      splenomegaly). Causes of splenomegaly were looked into 100 adult patients with
      splenomegaly, admitted over a period of ten months in a teaching hospital in
      South India. Patients having ascites were excluded from the study. Malaria was
      the commonest cause of splenomegaly, observed in 22 patients. Other causes, in
      order of importance, were chronic myeloid leukaemia (n=11), non-cirrhotic portal
      fibrosis (n=9), enteric fever (n=9), cirrhosis of liver (n=8) and hyper-reactive
      malarial splenomegaly also called as tropical splenomegaly syndrome (n=7) and so
      on. Hyper-reactive malarial splenomegaly was the commonest cause (7 of 24
      patients) of massive splenomegaly. Twenty-three patients had splenomegaly of
      indeterminate origin ie, cause could not be detected on first assessment.
      Detailed re-evaluation with repeat investigations including liver biopsy revealed
      the causes as follows: Hyper-reactive malarial splenomegaly -7 (30.4%), non
      cirrhotic portal fibrosis - 4 (17.4%), cirrhosis of liver - 4 (17.4%) and iron
      deficiency anaemia - 5 (21.7%). In 3 patients (13.0%), no diagnosis could be
      arrived at despite best efforts. Obscure splenomegalies may be due to conditions
      like hyper-reactive malarial splenomegaly, non-cirrhotic portal fibrosis, iron
      deficiency anaemia, and even cirrhosis of liver, while malaria is still the most
      important cause of splenomegaly in India. Whereas the overall incidence of hyper
      reactive malarial splenomegaly was only 7% in this study, it stood as the leading
      cause (29.2%), when analysed among patients with massive splenomegaly. Liver
      biopsy should be performed in all cases of obscure splenomegaly to arrive at the
      final diagnosis.

PMID- 18712134
TI  - Time trends of paediatric HIV infection in North India.
AB  - Paediatric HIV infection continues to pose a serious threat in the developing
      world. While in the developed world, mother to child transmission has been
      reduced to less than 3%, in India no regular zidovudine (azidothymidine)
      intervention programmes operate. Some 20 million babies are born each year and
      the number of infected babies could be >50,000 per year. The present study was
      designed to assess the change, if any, in the time trends of HIV infection in
      children over the last 15 years as observed at the surveillance centre attached
      to Nehru Hospital, Chandigarh. All patients reporting to the surveillance centre
      at the PGIME&R, Chandigarh were subjected to a detailed history and screened for
      HIV by the three tests protocol recommended by the WHO. In babies under 18 months
      of age, viral load assay or DNA analysis was done to confirm infection.
      Timetrends were ascertained over a 15-year period to assess the impact of
      information, education and communication programme launched by National AIDS
      Control Organisation. Data indicates that the total number of HIV positive cases
      increased 10-fold over the last 10 years. During 1991, 41 cases were recorded;
      the number increased to 439 in year 2001, and 574 in 2004 (r=0.98). A similar
      trend was observed in the paediatric age group. During the initial 5 years ie,
      1987 to 1992 only 7 paediatric cases were documented positive while the number
      increased to 45 in the year 2001 to 64 in the year 2004 with a cumulative figure
      of 323 children. Linear regression analysis showed a highly significant trend
      (r=0.94). Out of the 323 cases, 44.6% were symptomatic. Maximum number of babies
      were observed in the age group of 3-5 years. Thirty-nine patients (12%) had
      acquired the infection through blood. Thus the information, education and
      communication programme has had very little impact on the HIV epidemic and it
      calls for urgent antiretroviral intervention in antenatal mothers to control the
      emerging paediatric HIV epidemic.

PMID- 18712135
TI  - Rheumatological manifestations of leprosy.
AB  - Rheumatological manifestations are common in leprosy. A study was conducted among
      30 patients to observe the prevalence and spectrum of rheumatological
      manifestations in leprosy. Seventeen patients were referred from leprosy clinic
      from 287 consecutive leprosy cases and 13 patients presented de novo at the
      rheumatology clinic and later diagnosed to have leprosy. In the first group, the
      most common manifestation was small and large joints polyarthritis resembling
      rheumatoid arthritis found in 64.7% cases and in the second group tenosynovitis
      (38.5%) was the commonest. Rheumatoid factor was positive in 60% cases.

PMID- 18712136
TI  - Leucocyte and lymphocyte count in cases of bird flu infection in Thailand.
AB  - Bird flu or avian flu is a new emerging Infectious disease. The H5N1 virus has
      not only affected the fowls but also the human beings. Severe disease with high
      mortality in humans in Vietnam and Thailand are reported. This mini-study was
      undertaken in order to document the Impact of bird flu infection on leucocyte and
      lymphocyte counts among patients of Thailand. This study was designed as a
      descriptive retrospective study. A literature review on the papers concerning
      human bird flu in Thailand was performed. According to this study, there are 6
      cases covering 12 Thai patients with confirmed diagnosis of bird flu. However,
      the complete data were available on only 6 patients. The reported leucocyte count
      ranges from 1,200 cells/cmm to 5,680 cells/cmm and the lymphocyte count ranges
      from 454 cells/ cmm to 1,440 cells/cmm. The average leucocyte and lymphocyte
      counts equalled to 3,230.0 +/- 1,552.7 cells/cmm and 748.7 +/- 348.5 cells/cmm,
      respectively. According to this study, low lymphocyte count is common. This can
      support the previous observation for the lymphocyte suppression effect of H5N1
      virus.

PMID- 18712137
TI  - Communication strategies for organ donation.
AB  - A country, state or hospital may have the latest medical technology and
      infrastructure as well as qualified professionals for organ transplantation, but
      unless there is an adequate donor population the waiting lists for transplants
      will continue to be long and for some patients, hopeless. Public and professional
      awareness programmes are key factor in the donation process. Social education
      that explains the life-saving benefits of organ transplantation, the enormous
      need for organ donation, the concept of brain death and religious teachings
      related to these issues is vital for creating a conducive environment for the
      organ transplant co-ordinator or physician soliciting the donation. The education
      of hospital medical, nursing and administrative personnel is also essential to
      both miximise opportunities for donation, as well as to prevent loss of potential
      organs after donor consent. Other target populations are medical examiners or
      coroners, and police personnel under whose jurisdiction the donations occur, as
      their co-operation and guidance is necessary for meeting statutory requirements.
      The involvement of government officials and politicians is also valuable, as
      their active intervention is essential for the introduction and amendment of
      rules and laws to promote the donation and transplantation of organs. The present
      paper describes communication strategies for the development of an efficient
      education plan that will provide information about organ transplantation, explain
      the desired outcome, address potential queries, misconceptions or obstacles, and
      identify potential sources of support.

PMID- 18712138
TI  - An overview/update IMA GFATM RNTCP PPM project.
AB  - The existence of tuberculosis (TB) can be found in the bones of prehistoric man,
      found in Germany. Hippocrates (460-377 BC) also gave some imputs regarding the
      age-old TB. As regarding TB control history, some drugs were advised, but those
      drugs appear funny to present day physicians. Organised efforts to combat TB came
      into origin in late 1930s. In phase I establishment of sanatoria and TB clinics
      came into existence, then TB Association of India came into the picture, followed
      with direct initiative by the government. Phase II dealt with three decades of
      the National TB Control Programme. WHO declared TB is a global emergency. RNTCP
      is an application of WHO recommended DOTS strategy. Full implementation of the
      DOTS strategy remains the priority to control TB. Performance of RNTCP is more
      than statistactory.

PMID- 18712139
TI  - Intralobar sequestration with cystic adenomatoid malformation and atypia.
AB  - Pulmonary sequestration and congenital cystic adenomatoid malformation are
      infrequent congenital lung disease and the combination of these two entities is
      rare. Here a case of left pulmonary sequestration with congenital cystic
      adenomatoid malformation in an asymptomatic elderly woman who presented with
      recent massive haemoptysis is reported. Fine needle aspiration cytology showed
      hypercellularity with micro-acinar pattern and mild pleomorphism. Computerised
      tomography scan depicted a round mass with rim of peripheral enhancement at left
      lower lobe of the lung. Intra-operative findings were suggestive of an intralobar
      sequestration with multiple aberrant vascularisation. Histologically intralobar
      sequestration was associated with congenital cystic adenomatoid malformation and
      epithelial atypia.

PMID- 18712140
TI  - Glycogen storage disease type 1--an unusual cause of unconsciousness.

PMID- 18712141
TI  - Quality management in clinical practice: role of stakeholders.

PMID- 18712143
TI  - New challenges in dental education.

PMID- 18712142
TI  - Evaluation of fixed dose combination (FDC) of telmisartan+ramipril usage in
      patients with micro-albuminuria and persistent hypertension: A TRIUMPH study.
AB  - Micro-albuminuria is a marker for declining kidney function and predicts
      increasing cardiovascular risk especially in diabetic hypertensives. Angiotensin
      receptor blockers and angiotensin-converting enzyme inhibitors may slow the
      progression of proteinuric kidney disease and thus would be valuable in these
      high risk patients. The present study was undertaken to assess the efficacy and
      tolerability of a fixed dose combination (FDC) of telmisartan and ramipril in
      adult Indian patients with sustained stage 2 hypertension, comorbidities and
      micro-albuminuria. A total 382 patients were enrolled in this multicentric,
      prospective open, non-comparative phase IV postmarketing surveillance study by 40
      physicians in India and treated with FDC of telmisartan 40 mg+ ramipril 5 mg once
      daily for 12 weeks. A total 370 patients completed the study but 12 patients were
      lost to follow-up and considered as drop-outs. There was a significant (p<0.05)
      reduction in the systolic blood pressure (SBP) from 170.89 at baseline to 132. 77
      mm Hg at week 12 and diastolic blood pressure (DBP) from 104.47 to 83.30 mm Hg at
      the end of 12 weeks therapy as well as urine albumin levels from 186.25 mg/24
      hour to 62.42 mg/24-hour (66.49%) at the end of 12 weeks. Overall assessment of
      treatment was rated as good to excellent in 87.3% and fair in 11.4% patients. The
      most common adverse event reported was cough (5.2%). Results of the present study
      indicate that the FDC of telmisartan+ramipril brings about significant reductions
      in the systolic and diastolic blood pressure as well as urine albumin excretion.

PMID- 18712144
TI  - Economic aspects of dental education.

PMID- 18712145
TI  - Challenges in meeting future faculty recruitment and retention needs.

PMID- 18712146
TI  - Addressing the challenges in student recruitment.

PMID- 18712147
TI  - Introducing critical thinking into dental education.

PMID- 18712148
TI  - Teaching evidence-based decision-making versus experience-based dentistry.

PMID- 18712149
TI  - Use of computerized technology in clinical dental education.

PMID- 18712150
TI  - Alpha Omega Foundation of Canada: history.

PMID- 18712151
TI  - Having and enabling free will.

PMID- 18712152
TI  - Department of Oral Medicine.

PMID- 18712153
TI  - Transverse--Harris--lines in a skeletal population from the 1711 Danish plague
      site.
AB  - This study examines the occurrence and distribution of transverse lines in
      skeletal remains from the Copenhagen site, a plague cemetery dated 1711 AD. A
      relatively low frequency for evidence of line formation was observed in the
      individuals comprising the total sample and no transverse lines were present in
      the subadult category. This paper addresses the pattern of transverse line
      occurrence and cohort-specific distribution in a plague sample in light of the
      multiple factors influencing line formation and resorption and discusses the
      significance of transverse lines as measures of non-specific acute stress in
      archaeologically derived populations.

PMID- 18712154
TI  - Craniometric measurements of artificial cranial deformations in Eastern European
      skulls.
AB  - Standardized lateral cephalograms of eleven skulls with artificial cranial
      deformations from Eastern Europe and twenty normal skulls from the same
      population were made, digitized and imported into the AutoCAD 2005 computer
      program. The x- and y-coordinates of defined measuring points were determined and
      angle measurements were made. The form difference of the skulls was tested with
      the Euclidean Distance Matrix Analysis (EDMA) and the difference of the angle
      measurements were compared statistically using the non-parametric Mann-Whitney
      test. All deformed skulls belonged to the tabular fronto-occipital type of
      deformation. The results of the EDMA and the angle measurements indicated
      significant differences for the neurocranium and the facial cranium in height
      between the normal and the deformed skulls, but not in the cranial length. It can
      be concluded that in Eastern Europe one method of cranial molding was used. The
      deformation of the neurocranium also affected the development of the facial
      cranium regarding facial height. This may indicate a dependency of the
      developmental fields of the neurocranium and facial cranium.

PMID- 18712155
TI  - Os trigonum syndrome in ancient Anatolian settlements.
AB  - An os trigonum is a small, round bone situated just behind the ankle joint.
      Clinical research shows that the os trigonum is present in about 5-15 % of normal
      feet. It occurs when one part of the bone does not fuse with the rest of the
      talus during growth. The present study is made on the skeletons, which were found
      in the Karagundiiz, Dilkaya and Van Kalesi-Eski Van Sehri settlements, Van
      province, Anatolia, dated in the Middle Ages. In this study 228 skeletons were
      examined, 120 males and 108 females. 376 tall were studied: 227 from
      Karagiindtiz, 93 from Dilkaya, and 56 from Van Kalesi-Eski Van Sehri. The
      percentage of the os trigonum syndrome was recorded as 6.6 %.

PMID- 18712156
TI  - The mobile Condylus tertius occipitalis and fractures of the hypochordal clasp.
AB  - The Condylus tertius is defined as a small bony hunch on the anterior surface of
      the clivus. Its presence means an enormous functional impairment of the upper
      head joint, looking at the 3-point-contact between the skull base and the upper
      cervical vertebrae. In 10 of the 2000 forensic examined bodies, analyses of neck
      vertebra + skull base revealed this feature. The origin of these findings is
      discussed, as stated in the literature of embryology, to be a suboccipital
      hypochordal plate. So in one of the cases the condylus was found at the
      hypochordal plate itself whereas the so-called socket was lying at the margin of
      the clivus. In three cases there was found a free body between the apex of the
      Dens and the Clivus forming a mobile Condylus tertius. In our opinion its
      position varies over the anterior arch of the atlas and the apex of the dens as a
      result of rotatory forces between the atlas and axis and physiological strain.
      Examples are given to elucidate this. There is a difference in the
      differentiation of the deposited material according to functional demand. A
      pressure bed (i.e. a Condylus tertius) is formed when a bony structure is
      deposited on the clivus. This functional prospect relativises the hypothesis of a
      purely constitutional genesis of the Condylus tertius. A fracture of the
      hypochordal clasp being joined with a bony connection to the anterior atlantic
      arch is described for the first time.

PMID- 18712157
TI  - Facial image of Biblical Jews from Israel.
AB  - The present report deals with reconstructing the facial shapes of ancient
      inhabitants of Israel based on their cranial remains. The skulls of a male from
      the Hellenistic period and a female from the Roman period have been
      reconstructed. They were restored using the most recently developed programs in
      anthropological facial reconstruction, especially that of the Institute of
      Ethnology and Anthropology of the Russian Academy of Sciences (Balueva &
      Veselovskaya 2004). The basic craniometrical measurements of the two skulls were
      measured according to Martin & Saller (1957) and compared to the data from three
      ancient populations of Israel described by Arensburg et al. (1980): that of the
      Hellenistic period dating from 332 to 37 B.C., that of the Roman period, from 37
      B.C. to 324 C.E., and that of the Byzantine period that continued until the Arab
      conquest in 640 C.E. Most of this osteological material was excavated in the
      Jordan River and the Dead Sea areas. A sample from the XVIIth century Jews from
      Prague (Matiegka 1926) was also used for osteometrical comparisons. The present
      study will characterize not only the osteological morphology of the material, but
      also the facial appearance of ancient inhabitants of Israel. From an
      anthropometric point of view, the two skulls studied here definitely belong to
      the same sample from the Hellenistic, Roman, and Byzantine populations of Israel
      as well as from Jews from Prague. Based on its facial reconstruction, the male
      skull may belong to the large Mediterranean group that inhabited this area from
      historic to modern times. The female skull also exhibits all the Mediterranean
      features but, in addition, probably some equatorial (African) mixture manifested
      by the shape of the reconstructed nose and the facial prognatism.

PMID- 18712158
TI  - Genetic polymorphisms at three loci in two populations of Manipur, India.
AB  - The Phayengs and Khurkhuls are sections of the Meiteis, the largest community in
      Manipur, India. Racially they are Mongoloids, and marry mostly among themselves.
      The present study reveals the frequencies of ABO blood groups as A1 (36.54%), B
      (28.85%), O (25.96%) and A1B (8.65%) in the Phayengs (n = 124) and A1 (39.84%), B
      (21.14%), O (22.76%) and A1B (16.26 %) in the Khurkhuls (n = 123). The subtype A2
      is completely absent in both. The gene frequencies are ABO*A1 = 0.262, ABO*B =
      0.212 and ABO*O = 0.526 for the Phayeng and ABO*A1 = 0.334, ABO*B = 0.206, ABO*O
      = 0.526 among the Khurkhuls. The Phayengs show a frequency of Rh negatives as
      1.92%, the frequency of the RH*d allele being 0.139. The incidence of HB E is
      38.46% resulting into the frequency of HB*E = 0.266. This is the highest value so
      far reported from Manipur State. No Rh(D) negative individuals have been
      encountered among the Khurkhuls, and the incidence of HB E is 16.26%, the
      frequency of HB*E being 0.085.

PMID- 18712159
TI  - Relationships between blood pressure, polymorphism of angiotensin-converting
      enzyme (ACE), body composition and biochemical characteristics in elderly
      Slovaks.
AB  - Epidemiological studies have demonstrated that several specific environmental
      factors and candidate genes influence the human variation in blood pressure. The
      aim of this study was to investigate variables associated with blood pressure;
      with a particular emphasis on the differences in insertion/deletion (I/D)
      polymorphism of the human angiotensin-converting enzyme (ACE), the body
      composition and the recognized risk factors for atherosclerosis among elderly
      males and females. A total of 374 participants (174 males and 200 females) aged
      from 60 to 90 years were recruited from different parts of Slovakia. The elderly
      were not bed-ridden, nor mentally impaired, they were able to manage their daily
      activities by themselves. The ACE I/D polymorphism was determined by PCR
      amplification of the ACE gene sequence. Body composition variables were obtained
      by bioelectrical impedance analysis, using the BIA 101 soft tissue-body impedance
      analyzer (Akern, S.r.l.). The subjects were determined to be hypertensive (blood
      pressure > or = 140/90 mm Hg) or normotensive (blood pressure < or = 140/90 mm Hg
      ). These two subgroups of males and females did not differ significantly in their
      mean ages. As expected, the hypertensive subjects of both sexes showed
      significantly higher mean values in systolic (SBP) and diastolic blood pressure
      (DBP), in body mass index (BMI), and in the mean values of their plasma glucose
      and extracellular water (ECW). The genotype distribution and allele frequencies
      in the whole sample (D = 0.5474, I = 0.4526) fell within the Hardy-Weinberg
      equilibrium. The frequency of the deleterious D allele in the normotensive
      (0.5532) and hypertensive (0.5516) subjects was not significantly different. The
      ACE I/D genotypes did not associate either with the systolic (p = 0.836) or
      diastolic BP (p = 0.629). From the other variables that may induce differences in
      blood pressure, a statistical effect was detected for glucose, Na/K, and Apo
      A1/ApoB ratios and physical activity on SBP, and for ApoA1, physical activity,
      BMI and total cholesterol on DBP.

PMID- 18712160
TI  - Comparing sensory experience in bitter taste perception of phenylthiocarbamide
      within and between human twins and singletons: intrapair differences in
      thresholds and genetic variance estimates.
AB  - BACKGROUND: Quantitative genetic studies revealed that not all of the phenotypic
      variance in PTC taste perception is heritable. AIM: To study quantitative
      variations in PTC tasting ability in twins and to estimate heritability of PTC
      taste perception on the taste of twin data on males and females sexes separately.
      SUBJECTS AND METHODS: The data for PTC taste sensitivity following the classic
      method of Harris & Kalmus (1949) were collected on a sample of 141 twin pairs (66
      MZ and 75 DZ) and 275 singletons (128 males and 147 females) from Chandigarh,
      India. Genetic analyses were performed following Christian (1979), Donner (1986)
      and Sham (1998). RESULTS: Frequency of non-tasters was similar in twins (33 %)
      and singletons (32 %), but significant sex differences were observed. No
      differences were found between zygosities for mean thresholds. Similarly, no
      evidence of variance heterogeneity and environmental covariance was seen between
      zygosities. Since no basic assumption of the twin method was found violated,
      within-pair estimates of genetic variance would be unbiased. These estimates were
      highly significant in both males and females. However, dominance and additive
      components of genetic variance were found to differ between sexes. CONCLUSION:
      PTC thresholds do not seem to be significantly affected by environmental factors
      as no variance inequality was observed between twin zygosities. Intensity of
      bitterness (scalar dimensions) of PTC is a separate trait having no commonality
      with the genetic basis of recognition threshold for PTC tasting ability. The
      receptors recognizing bitter taste are different from the receptors determining
      intensity of taste. The absolute difference between co-twins in PTC thresholds
      can be used as a simple tool in the twin zygosity diagnosis. The results show
      that none of the MZ co-twins had manifested difference of more than 3 in their
      PTC threshold.

PMID- 18712161
TI  - The influence of basic body and hand anthropometry on the results of different
      throwing tests in young handball and basketball players.
AB  - The aim of this study was to investigate the relationships between basic body and
      specific hand anthropometric parameters with some specific and non-specific throw
      test results in young male handball and basketball players. The subjects included
      34 handball and 38 basketball players of the 10-11 years old age group, 39
      handball and 22 basketball players of the 12-13 years old age group and 39
      handball players of the 14-15 years old age group. Body height and body mass,
      arms' span, height with outstretched hands and sitting height were the basic
      anthropometric parameters to be measured. For hand anthropometry, 15 specific
      hand parameters were measured using the method presented by Visnapuu & Jurimae
      (2007). Stepwise multiple regression analysis indicated that medicine ball throw
      results in the youngest age group are highly dependent on the body height
      (handball players) and body mass (basketball players). In the middle age group,
      the most important parameter from the hand anthropometry is TL (handball) or
      height with outstretched hands (basketball). In the oldest group of handball
      players, the medicine ball throw results were dependent on the P2 from hand
      anthropometry and sitting height. Quite different anthropometric parameters
      appeared to influence the handball or basketball throw results. In the youngest
      age group, most important were body height (handball) or LFL (basketball). In the
      middle age group, the most important was height with outstretched hands and in
      the oldest handball players LFL and sitting height. Handball or basketball pass
      on speed depended on the combination of body mass and FS5 and body height with
      height with outstretched hands (even 61.40%, R2 x 100) in the oldest age group.
      The results of passing the handball or basketball on precision were dependent on
      body height and P3 or P1 among basketball players in the youngest group. In the
      middle age group the combination of FS3 and body mass and LFL and height with
      outstretched hands were the most influential. Anthropometric parameters influence
      on the passing of the ball on speed or precision is lower in handball players
      compared with basketball players. Our conclusion is that the basic anthropometric
      parameters are slightly more important than hand anthropometry that influenced
      different throw tests results in young handball and basketball players.

PMID- 18712162
TI  - Childlessness in old age--an anthropological approach to a current problem.
AB  - The amount of aged and old aged people is increasing markedly in all
      industrialized nations as well as in many developing countries. Additionally to
      the increasing life expectancy, a trend towards voluntary childlessness is
      observable. This trend will not only result in a continuing change of the
      population structure, it will also result in several individual problems of the
      aged population caused by childlessness. In the present paper the possible
      effects of voluntary childlessness on quality of life during old age are
      discussed from an anthropological point of view.

PMID- 18712163
TI  - 85 years from the birth of the Estonian anthropologist Karin Mark.

PMID- 18712164
TI  - Characterization of a new rat model of head and neck squamous cell carcinoma.
AB  - AIM: To develop and characterize by imaging and pathological examination a new
      immunocompetent rat model of head and neck squamous cell carcinoma (HNSCC). STUDY
      DESIGN: Prospective animal research. MATERIALS AND METHODS: Frozen specimens of
      HNSCC induced chemically by 4-nitroquinoline 1 oxide (4-NQO) in Sprague Dawley
      rats were used for the first graft. Serial allografts were then performed with
      fresh specimens of tumor in twenty-five Sprague Dawley rats. A specimen of tumor
      (100 mm3) was picked up by head and neck dissection during an autopsy. The graft
      was performed in a subcutaneous manner, in the ventral part of the neck, using an
      incision of 4 mm, through the masseter muscle. Tumors were clinically measured
      once a week and volumes were calculated. 2-[18F]Fluoro-2-deoxy-D-glucose positron
      emission tomography coupled with computed tomography (FDG-PET/CT) was performed
      on days 14 and 30 after the graft. Rats were euthanized and pathological features
      were assessed using hematoxylin-eosin (HE) staining and immunohistochemistry
      markers to characterize the tumor. RESULTS: An 80% take rate was achieved using
      fresh tumor specimens. Tumors grew rapidly; the mean tumoral volume was 1.013 cm3
      on day 14 and 7.994 cm3 on day 30. FDG-PET/CT imaging targeted regions of
      metabolically active tumor. It showed a uniform uptake of 18F-FDG on day 14 and a
      large area of central necrosis on day 30. Pathological examinations showed a
      typical squamous cell carcinoma, with similar immunohistochemical analyses to the
      human squamous cell carcinoma. CONCLUSION: We propose a new allograft HNSCC rat
      model which is easily reproducible and rapidly obtained in comparison to that
      induced chemically with 4-NQO. This model was developed in immunocompetent rats,
      with similar conditions to human carcinogenesis and could be used for testing new
      therapeutics.

PMID- 18712165
TI  - Alteration of inflammatory cytokine production in the injured central nervous
      system of tenascin-deficient mice.
AB  - Although tenascin-C (TN) is highly up-regulated during the proliferation of
      reactive astrocytes, little is known about the function of TN at injury sites in
      the central nervous system (CNS). Here, the function of TN-expressing astrocytes
      in the injured brain was investigated by analyzing TN-deficient mice with stab
      wound injuries of the cerebral cortex. Glial fibrillary acid protein expression
      after injury was down-regulated earlier in TN-deficient mice than in wild-type
      (WT) mice. To evaluate immune responses in the injured CNS in the absence of TN,
      inflammatory cytokine production was examined after unilateral stab injuries of
      the cerebral cortex in TN-deficient and WT mice. The expression of interleukin
      (IL)-1beta, tumor necrosis factor-a and IL-6 was higher in TN-deficient mice,
      whereas levels of IL-4 and granulocyte colony-stimulating factor were lower in TN
      deficient mice than WT mice. Our findings suggest that TN helps to regulate
      production of inflammatory cytokines in the injured brain.

PMID- 18712166
TI  - Regulation of matrix metalloproteinases (MMP)-2/-9 expression in eosinophilic
      chronic rhinosinusitis--cell culture by interleukin-5 and -13?
AB  - BACKGROUND: Eosinophils are a prominent immunological feature of chronic
      rhinosinusitis (CRS). Cytokines in the respiratory mucosa may be the key to upper
      airway pathophysiology. Matrix metalloproteinases (MMP) represent an entire group
      of Zn2+ dependent endopeptidases with the potential to alter the extracellular
      matrix (ECM). In this study epithelial cultures of CRS were treated with
      interleukin (IL)-5 or IL-13 and subsequent levels of metalloproteinases were
      determined. MATERIALS AND METHODS: The cells for CRS culture were obtained from
      patients undergoing functional endoscopic sinus surgery. After 8-72 hours
      incubation with 0.2-0.4 ng/ml IL-5 or 3-6 ng/ml IL-13, the expression of the MMP
      2 and -9 in the CRS cultures was analysed. RESULTS: After 72 hours incubation
      with IL-5, the relative levels of MMP-2 showed no significant alteration in
      protein expression in comparison with the control groups. Incubation with IL-13
      revealed a statistically insignificant decrease of the relative MMP-9 expression
      in ECRS compared to the control group (p>0.1). CONCLUSION: Alterations of MMP-2
      and -9 expression may play a role in ECRS, but the association with IL-5 and IL
      13 remains unclear.

PMID- 18712167
TI  - Radiation and secondary immune response to lipopolysaccharide.
AB  - BACKGROUND: The purpose of this study was to determine whether secondary immune
      responses to lipopolysaccharide (LPS) were altered by exposure to radiation.
      MATERIALS AND METHODS: C57BL/6 mice were irradiated (60Co, gamma-rays) to 0 or 3
      Gray (Gy) and injected intraperitoneally with LPS on days 10 and 42 thereafter.
      Subsets were euthanized 0-14 days after the second injection for analyses.
      RESULTS: The data show numerous radiation-induced effects, as well as some
      significant interactions among radiation, LPS, and day of analysis. Among the
      most striking were changes in thymus mass, circulating lymphocytes, monocytes,
      granulocytes, and specific lymphocyte subpopulations, erythrocyte counts,
      hematocrit, and platelet counts and volume. Spontaneous blastogenesis and
      oxidative burst capacity of phagocytic cells, however, were relatively normal.
      CONCLUSION: The findings indicate that exposure to radiation at a spaceflight
      relevant dose can influence the distribution of certain leukocyte populations in
      response to a secondary challenge with LPS.

PMID- 18712168
TI  - Corticosterone concentrations in blood and excretion in faeces after ACTH
      administration in male Sprague-Dawley rats.
AB  - The aim of the present study was to analyse the corticosterone response to
      exogenous ACTH in the circulation of catheterised male rats and to investigate
      the sensitivity of faecal corticosterone output as a measure of preceding
      elevated levels in the circulation. A total of 21 adult male Sprague-Dawley rats
      permanently catheterised (v. jugularis externa for intravenous administration of
      ACTH and a. carotis communis for blood sampling), were used. Administration of
      both 10 and 100 microg/kg ACTH resulted in a rapid and pronounced corticosterone
      increase three minutes after injection (226 and 220 ng/ml, respectively), but the
      duration of the response was different. In the 10 microg/kg group, corticosterone
      levels were significantly elevated for 3-90 min after injection, while in the 100
      microg/kg group, the levels remained elevated for 240 min after injection. In
      faeces, a significant increase during eight hours after ACTH injection was found
      in the group treated with 100 microg/kg, but not in the group treated with 10
      microg/kg. In conclusion, quantification of faecal excretion of corticosteroids
      is a useful non-invasive measure of prior substantial stress (e.g. surgery), but
      not sufficiently sensitive to reveal minor stress or acute stress of short
      duration.

PMID- 18712169
TI  - Review. Indole-3-carbinol as a chemoprotective agent in breast and prostate
      cancer.
AB  - Assessment of the oral use of indole-3-carbinol (I3C) as a chemoprotective
      compound has not sufficiently considered the chemical instability of I3C. This
      review addresses the question of whether I3C is directly active in its own right
      or only serves as a precursor, with all of the biological responses coming from
      reaction products arising in culture media and in the presence of stomach acid.
      Because of the rapid conversion of I3C into its dimer. diindolylmethane (DIM),
      and trimers very little circulating I3C is present following oral use to effect a
      biological response. Reports of toxicity associated with oral use of I3C relate
      to unfavorable enzyme induction, which can be attributed to non-DIM reaction
      products. Because DIM provides a predictable, safer response than the melange of
      compounds derived from I3C DIM should be regarded as the chemoprotective compound
      of choice.

PMID- 18712170
TI  - Progestational agents prevent preterm birth induced by a nitric oxide synthesis
      inhibitor in the mouse.
AB  - BACKGROUND: The ability of the nitric oxide (NO) synthesis inhibitor NG-nitro-L
      arginine methyl ester (L-NAME) to induce preterm parturition in the mouse has
      been previously documented. The present study tested the ability of
      progestational agents to prevent preterm birth induced by L-NAME. MATERIALS AND
      METHODS: L-NAME was administered subcutaneously at 90 mg/kg on gestation day 16.
      Progesterone, medroxyprogesterone acetate and hydroxyprogesterone caproate were
      administered subcutaneously at 0 (vehicle), 5 or 10 mg/kg on gestation day 16 one
      hour before L-NAME and on day 17. Parturition was considered preterm if occurring
      before gestation day 18. RESULTS: Following treatment with L-NAME alone, 56.5% of
      the pregnant animals delivered before term. Treatment with progesterone,
      medroxyprogesterone acetate or hydroxyprogesterone caproate at 5 mg/kg or 10
      mg/kg significantly and comparably reduced the rate of preterm birth caused by L
      NAME. CONCLUSION: Progestational agents are able to reduce preterm births induced
      by nitric oxide synthase (NOS) inhibition.

PMID- 18712171
TI  - 10 years' experience in fragile X testing among mentally retarded individuals in
      Greece: a molecular and epidemiological approach.
AB  - Fragile X syndrome, the second most common genetic cause of mental retardation,
      is due to the expansion of a trinucleotide repeat (CGG)n within the first exon of
      the FMR-1 gene. Molecular genetic analysis provides accurate diagnosis and
      facilitates genetic counselling and prenatal testing. Screening for the fragile X
      mutation in a sample of 3,888 individuals in Greece is reported: 1,755 children
      with non-specific mental retardation, 1,733 parents and other family members and
      400 normal individuals. Molecular analysis allowed for the identification and
      characterization of 52 fragile X families confirming the clinical diagnosis in 57
      males and 4 females. Sixty-six female carriers (6 mentally retarded) and 4 normal
      transmitting males were also identified. Four severely retarded males and their
      mothers carried unmethylated premutations, while a moderately retarded girl had a
      deletion of approximately equal to 150 bp. Overall sizing of the CGG repeat
      produced an allele distribution of 6-58 CGG repeats (mean 28-30), similar to that
      in other Caucasian populations.

PMID- 18712172
TI  - Possible relation between histone 3 and cytokeratin 18 in human hepatocellular
      carcinoma.
AB  - BACKGROUND: Previously we found some low molecular weight proteins identified as
      histone in hepatocelluar carcinoma. Our objective was to clarify whether the
      coimmunoprecipitation of histone and cytokeratin 18 was an artifact or not.
      MATERIALS AND METHODS: Histone 3 and cytokeratin 18 were investigated in three
      cases of human hepatocellular carcinoma and one case of normal liver tissue.
      Nuclei of the tissues were isolated; the proteins inside the nuclei were analyzed
      by Western blot. RESULTS: The results revealed histone was co-immunoprecipitated
      with cytokeratin 18 in hepatocellular carcinoma. It was speculated that
      modulation of the cytoskeleton in human hepatocellular carcinoma might disturb
      the organization of the nucleoskeleton. The unstable nucleoskeleton might further
      cause instability and fragility of nuclei, thus possibly exposing the histone and
      co-immunoprecipitating it with cytokeratin 18. CONCLUSION: The evidence might
      indicate that expression of histone 3 was highly related to modulation of
      cytokeratin 18 and might play an important role in tumorigenesis of
      hepatocellular carcinoma.

PMID- 18712173
TI  - Expression of extracellular matrix metalloproteinase (MMP-9), E-cadherin and
      proliferation-associated antigen Ki-67 and their reciprocal correlation in canine
      mammary adenocarcinomas.
AB  - BACKGROUND: The purpose of the present study was to determine the expression of
      the proteins related to tumour metastatic potential, including matrix
      metalloproteinase (MMP)-9 and E-cadherin, in correlation with the expression of
      proliferation-associated antigen (Ki-67) in canine mammary adenocarcinomas.
      MATERIALS AND METHODS: Material for the studies was obtained during surgery from
      35 dogs of various breeds, aged 7 to 16 years. Neoplastic tumours were verified
      by a pathologist. The studied proteins were detected by immunohistochemical
      reactions. The microphotographs of the studied tumours were subjected to computer
      assisted image analysis using MultiScaneBase V 14.02 software. RESULTS:
      Expression of MMP-9 was noted in almost 83% of the tumours, expression of E
      cadherin in 77% of tumours, while expression of Ki-67 antigen was detected in
      fewer than 26% of studied tumours. CONCLUSION: The positive correlation (r=0.375)
      between expressions of MMP-9 and Ki-67 and negative correlations between E
      cadherin and Ki-67 (r=-0.383) as well as between MMP-9 and E-cadherin (r=-0.45)
      could suggest that expression and biological significance of the studied markers
      in mammary adenocarcinomas in dogs resembles the pattern noted in ductal
      carcinoma, i.e. in the most frequent histological type of malignant tumour in
      humans. This may point to suitability of the animal model in studies on mechanism
      of neoplasia and metastases in humans.

PMID- 18712174
TI  - Antiviral, antibacterial and vitamin C-synergized radical-scavenging activity of
      Sasa senanensis Rehder extract.
AB  - Sasa senanensis Rehder extract (SE) showed slightly higher cytotoxicity against
      human squamous cell carcinoma cell lines and human glioblastoma cell lines, as
      compared with human oral normal cells (gingival fibroblast, pulp cell,
      periodontal ligament fibroblast), and was more cytotoxic to human myelogenous and
      T-cell leukemia cell lines. SE showed a bacteriostatic effect on Fusobacterium
      nucleatum and Prevotella intermedia, but almost completely eliminated hydrogen
      sulfide (H2S) and methyl mercaptan (CH3SH) produced by these bacteria. SE
      protected human T-cell leukemia MT-4 cells from the cytopathic effect of human
      immunodeficiency virus (HIV) infection, and its anti-HIV activity was much higher
      than that of tannins and flavonoids, comparable with that of natural and
      synthetic lignins. SE also protected the MDCK cells from the cytopathic effect of
      influenza virus infection. SE synergistically enhanced the superoxide anion and
      hydroxyl radical-scavenging activity of vitamin C. The present study suggests the
      functionality of SE as a complementary alternative medicine.

PMID- 18712175
TI  - APE1 and XRCC3 polymorphisms and myocardial infarction.
AB  - BACKGROUND: In most cells, DNA is regularly damaged by mutagens. Different DNA
      repair mechanisms operate on specific types of damaged DNA. When DNA damage
      resulting from free radicals is not repaired, it might lead to deteriorated gene
      expression, the development of a number of diseases such as cancer, diabetes,
      vascular diseases, and aging. In the present study, APE1 and XRCC3 gene
      polymorphisms were investigated in patients with myocardial infarction. MATERIALS
      AND METHODS: Forty-five first time elective coronary artery bypass grafting
      (CABG) patients with cardiopulmonary bypass (CPB) and 40 healthy individuals were
      studied. Gene polymorphisms were determined by a polymerase chain reaction
      restriction fragment length polymorphism method. RESULTS: For the APE1 gene, the
      AG genotype was significantly higher in the patient group than in the control
      group. The patient group had significantly more G carriers but there was no
      statistically significant difference between patient and control groups the A
      allele. The XRCC3 TT genotype was found to be significantly more frequent in the
      patient group than it was in the control group. CONCLUSION: The results of our
      study suggested that the XRCC3 gene TT genotype and the APE1 gene AG genotype
      might increase the risk of myocardial infarcts.

PMID- 18712176
TI  - Interleukin-2 inhalation therapy in renal cell cancer: a case report and review
      of the literature.
AB  - Renal cell carcinoma (RCC) is the most common malignancy of the kidney. One third
      of RCC presents metastatic disease at the time of diagnosis, usually leading to a
      fatal outcome. Small response rates were seen with most cytotoxic agents
      including gemcitabine and vinorelbine, whereas systemic therapy with high doses
      of interleukin 2 (IL-2) has been shown to provide durable complete remissions.
      However, in consideration of its severe toxicity, IL-2 immunotherapy is
      restricted to selected patients. Aerosol IL-2 has been introduced as an
      alternative therapy in cancer patients. However, only very few data are available
      on its use in patients with pulmonary metastatic RCC. This paper briefly
      summarizes current clinical experience with the use of inhaled IL-2 therapy,
      either as a single therapy or in combination with other treatments. In addition,
      we report on a male patient with pulmonary metastasized RCC who achieved a
      durable complete response to combined gemcitabine/vinorelbine and interleukin-2
      inhalation therapy.

PMID- 18712177
TI  - A color Doppler ultrasound-based comparative study between stavudine and non
      stavudine regimens in the onset of vascular lesions in HIV-1-positive patients.
AB  - BACKGROUND: The present study aimed to investigate the role of stavudine in the
      onset of premature vascular lesions using an ultrasound color Doppler evaluation
      of the carotid vessels. PATIENTS AND METHODS: A total of 266 patients were
      evaluated: 149 were treated with stavudine (group I) and 117 without stavudine
      (group II). RESULTS: Of the patients in group I, 41% exhibited vascular lesions
      vs. 26% in group II (p=0.0103). The two groups were further divided into
      subgroups Ia (stavudine and proteinase inhibitor, PI), Ib (stavudine and non
      nucleotidic reverse transcriptase inhibitor, NNRTI), IIa (PI, without stavudine)
      and IIb (NNRTI without stavudine). A higher prevalence of lesions emerged in
      group Ia, while group IIa were at higher risk of developing vascular lesions than
      groups Ib and IIb. CONCLUSION: Although stavudine per se does not seem to
      determine damage of the epiaortic vessels, the association of a PI with stavudine
      is related to a significantly higher rate of lesions.

PMID- 18712178
TI  - Review. Non-papillary urothelial lesions of the urinary bladder: morphological
      classification and immunohistochemical markers.
AB  - In the past quarter century, several nomenclature systems for non-papillary
      urothelial lesions of the urinary bladder have been proposed. The 1998 World
      Health Organization and International Society of Urological Pathology (WHO/ISUP)
      classification recommended a four-tier system for the subdivision of flat
      intraepithelial lesions of the bladder. This classification was adopted by the
      WHO in 1999 and revised in 2004. In 2002, a more detailed classification of flat
      urothelial lesions was based on the Ancona International Consultation. Each of
      these lesions was defined with strict morphological criteria to provide more
      accurate information to urologists in managing patients. However,
      immunohistochemical markers including proliferation markers, cytoskeletal
      proteins, growth factors and their related receptors, cell adhesion molecules and
      oncogene proteins are increasingly being used in order to differentiate
      histologically similar lesions.

PMID- 18712179
TI  - Skin grafting: comparative evaluation of two dressing techniques in selected body
      areas.
AB  - BACKGROUND: Skin grafting is a frequent surgical procedure used to reconstruct a
      soft-tissue deficit. Tie-over bolster dressing is the traditional technique made
      to fix the graft to the recipient area. This dressing does not always provide
      satisfactory results in some difficult body areas, with poor skin graft taking as
      an outcome. Here, we used a soft "polyurethane sponge" as a compressive tool.
      MATERIALS AND METHODS: A therapeutic protocol was used to select patients,
      splitting them into 2 groups: tie-over bolster dressing versus polyurethane
      sponge. Data analysis and calculation of sample size were performed using the
      Statistical Package for the Social Sciences Windows version 13.0. RESULTS: Of the
      106 patients treated by traditional compressive dressing, 11 had complications,
      thus achieving a success rate of 89.6%. Of the 106 patients treated by
      polyurethane sponge dressing, 3 had complications, providing a success rate of
      97.1%. CONCLUSION: Compared with the conventional tie-over dressing, the sponge
      dressing technique was demonstrated to be more successful in graft taking in
      selected areas.

PMID- 18712180
TI  - Postmeal portal flow variations in HCV-related chronic hepatitis and liver
      cirrhosis with and without hyperdynamic syndrome.
AB  - BACKGROUND: Doppler ultrasonography (US) of portal blood flow and portal flow
      volume (PFV) are useful to define changes in portal hemodynamics of patients with
      chronic liver diseases. The meal test with postmeal PFV measurements is generally
      accepted as a reproducible noninvasive test to evaluate the severity of portal
      hypertension. The aim of this study was to evaluate whether monitoring PFV
      changes after ingestion of a standard meal would be useful to characterize
      patients with chronic hepatitis or liver cirrhosis in the presence or absence of
      hyperdynamic syndrome (HS) characterized by elevated PFV, splenomegaly, systemic
      hypotension and/or increased cardiac output. PATIENTS AND METHODS: Thirty-seven
      patients (22 men and 15 women, median age 53 years) with hepatitis C virus
      infection and 20 healthy age- and sex-matched volunteers (Controls) were enrolled
      in the study. There were 19 (51.4%) patients with chronic hepatitis (Group A) and
      18 (48.6%) with ultrasonographic evidence of liver cirrhosis (Child-Pugh class
      B), 9 of whom had an HS (Group B) while the remainder (Group C) did not. Each
      patient underwent liver color Doppler US and the test was repeated 30, 60 and 90
      minutes after administration of a standard meal (300 kcal fluid meal containing
      12 g of proteins, 11.6 g of lipids and 36.8 g of carbohydrates). RESULTS: The
      baseline PFV did not differ (p=NS) between Controls and both Groups A and C,
      while the PFV of Group B patients was significantly (p<0.01) higher. After 30
      minutes, the PFV increased (p<0.01) both in Controls and Group A patients, while
      the differences were not significant in cirrhotic patients (Groups B and C). Our
      study confirmed that the postmeal PFV increases in both healthy individuals and
      in patients with chronic hepatitis, while in cirrhotic patients no significant
      changes occur. In conclusion, monitoring the portal blood flow in cirrhotic
      patients before and after administration of a standard meal might be a suitable
      test to evaluate potential disturbances of the flow itself. Moreover, the test
      could be useful to determine optimal pharmacological or surgical interventions
      aimed at restoring a better flow to the liver by reducing or favouring the
      occurrence of spontaneous mesenteric-systemic venous shunts.

PMID- 18712181
TI  - 18F-FDG PET/CT in myeloma with presumed solitary plasmocytoma of bone.
AB  - AIM: To evaluate the value of 18F-fluorodeoxy-glucose (FDG) positron emission
      tomography with computed tomography (PET/CT) in myeloma in patients presenting
      with a solitary plasmacytoma of bone (SPB). PATIENTS AND METHODS: Fourteen
      consecutive patients studied since 2006, all having a diagnosis of SPB before
      PET/CT imaging took part in this study. In 3 patients PET/CT was performed for
      staging while in the remaining 11 it was used to monitor therapy. PET/CT was
      performed using a dedicated tomograph 60-90 minutes after intravenous injection
      of 53 MBq/kg of 18F-FDG and the results were compared to other diagnostic
      procedures [radiographs and magnetic resonance imaging (MRI)], biopsy, and other
      available follow-up data. RESULTS: In 8/14 patients, PET/CT scans showed
      previously unsuspected sites of increased FDG accumulation. In 6/8 patients, FDG
      uptake was considered pathologic, depicting myeloma involvement in bone, while in
      the remaining cases, findings were considered incidental and not related to
      myeloma. PET findings attributed to myeloma were confirmed (i.e. true positives)
      in 6/6 cases (100%) and in all patients with findings reported as non-pathologic,
      myeloma was excluded (100% true negatives). CONCLUSION: Our preliminary data in a
      small number of cases suggests that there are a group of patients with SPB (local
      disease) in whom FDG PET/CT may detect other unsuspected sites of bone
      involvement, upstaging the extent of the disease. In these cases, SPB may be a
      local manifestation of multiple myeloma where other sites of involvement have
      eluded detection by other less sensitive imaging modalities (i.e. skeletal
      surveys) or anatomically restricted imaging (i.e., less than total body MR or
      CT). Finding other sites of involvement have significant implications for
      appropriate treatment of myeloma.

PMID- 18712182
TI  - Ultrastructural changes in regressing equine sarcoid tumours--mysterious role of
      mitochondria.
AB  - Mitochondrial changes of healing sarcoids were followed in 17 affected horses.
      Biopsies of this fibroblastic skin tumour were collected both before and during
      the treatment and tumour regression. The therapy consisted of the partial
      excision of tumours, repeated immunizations with autogenous polymerized tumour
      particles and supportive dietary treatment with stannic chloride and folic acid.
      Presence of transformed, electron-dense mitochondria in different phases of
      healing was studied by successive biopsy from regressing tumours. Additionally,
      the relation of these transformed mitochondria to the clinical status and
      behaviour of the tumours was evaluated. Transformed mitochondria were not found
      in the tumour tissue of the horses that had not been earlier treated by
      bioimmunotherapy, while after the therapy, all of the regressing tumours showed
      electron dense mitochondria. These changes were found significantly more in the
      margin of the regressing tumours than at the centre, i.e. at the site where the
      visible healing had further progressed. There was no difference between the
      numbers of transformed mitochondria in the horses with initially a primary or
      recurrent tumour. However, horses that developed recurrent disease after
      bioimmunotherapy showed significantly smaller numbers of electron-dense
      mitochondria as a response to bioimmunotherapy than the horses which did not
      experience relapse. Mitochondrial changes seem to be dynamically linked to the
      healing process and, additionally, may reflect prognosis.

PMID- 18712183
TI  - Malondialdehyde and protein carbonyl as biomarkers for oxidative stress and
      disease progression in patients with chronic myeloid leukemia.
AB  - BACKGROUND: Oxidative stress, a pervasive condition of an increased amount of
      free radicals, is now recognized to be prominent feature of various diseases and
      their progression. However, evidence for this association has often been lacking
      because of a lack of specific biomarkers and methods available to evaluate
      oxidative stress status in humans with disease conditions. Emphasis is now being
      placed on biomarkers of oxidative stress, which can be objectively measured and
      evaluated as indicators of normal biological and pathogenic processes. The aim of
      this study was to investigate the plasma levels of malondialdehyde (MDA) and
      protein carbonyl (PC) as biomarkers for oxidative stress and disease progression
      in patients with chronic myeloid leukemia (CML). MATERIALS AND METHODS: The study
      included 20 CML patients and 10 age-and sex-matched healthy control volunteers.
      The mean age of CML patients was 37.11+/-11.36 years and that of controls was
      31.07+/-7.60 years. RESULTS: There was a significant increase (p<0.05) in plasma
      MDA and PC levels in CML patients as compared to healthy volunteers. Our results
      also showed that plasma MDA and PC levels were significantly higher (p<0.001) in
      both chronic phase (CML-CP) and accelerated phase (CML-AP) as compared to healthy
      volunteers. During the follow-up of 12 months, two patients of CML-CP progressed
      to the accelerated phase. The mean plasma levels of MDA and PC in patients with
      CML-CP who progressed to CML-AP were found to be higher than in patients with CML
      CP who did not progress to the accelerated phase. CONCLUSION: Plasma MDA and PC
      appears to reflect the oxidative stress status and disease progression in CML and
      can be used as biomarkers for oxidative stress and disease progression.

PMID- 18712184
TI  - Review. EGFR mutations in non-small cell lung cancer--clinical implications.
AB  - The epidermal growth factor receptor (EGFR) family members seem to play a
      critical role in lung tumourigenesis and are overexpressed in 40-80% of non-small
      cell lung carcinoma (NSCLC) tumours. EGFR activation results in a series of
      downstream signaling events that mediate cancer cell growth, proliferation,
      motility, adhesion, invasion, apoptosis inhibition and metastasis as well as
      resistance to chemotherapy. Therefore, EGFR inhibitors seem to be an effective
      therapy for some patients with previously treated NSCLC. A thorough investigation
      of EGFR, its major signaling pathways, its identification and biology in NSCLC
      and the responsiveness to gefitinib, erlotinib and cetuximab in connection to
      EGFR mutations as well as the possible mechanisms of resistance to tyrosine
      kinase inhibitors is the scope of this review.

PMID- 18712185
TI  - Apolipoprotein J and leptin levels in patients with coronary heart disease.
AB  - BACKGROUND: Preliminary data suggest that apolipoprotein J (ApoJ) may play a role
      in the development and progression of atherosclerosis. Leptin, an adipose tissue
      hormone, exerts important cardiovascular effects. The association between serum
      ApoJ and leptin concentrations was assessed in patients with established or
      suspected coronary heart disease (CHD). PATIENTS AND METHODS: Serum ApoJ and
      leptin concentrations were evaluated in 67 CHD patients undergoing coronary
      angiography [54 individuals with significant (> or =50%) coronary artery stenosis
      and 13 patients without significant coronary artery stenosis on angiography].
      RESULTS: Serum ApoJ concentrations in patients with significant coronary artery
      stenosis were significantly higher than in those without (303.9+/-118.6 vs.
      121.2+/-37.5 microg/mL, respectively; p<0.001). The reverse pattern was observed
      for serum leptin levels (8.6+/-5.5 vs. 20.6+/-17.1 ng/ml, respectively; p=0.016).
      There was a significant negative correlation between ApoJ and leptin levels (r=
      0.353; p=0.003). CONCLUSION: ApoJ and leptin may be markers for CHD.

PMID- 18712186
TI  - Validity of the Developmental Test of Visual-Motor Integration Supplemental
      Developmental Test of Visual Perception.
AB  - Visual perceptual skills of school-age children are often assessed using the
      Supplemental Developmental Test of Visual Perception of the Developmental Test of
      Visual-Motor Integration. The study purpose was to consider the construct
      validity of this test by evaluating its scalability (interval level measurement),
      unidimensionality, differential item functioning, and hierarchical ordering of
      its items. Visual perceptual performance scores from a sample of 356 typically
      developing children (171 boys and 185 girls ages 5 to 11 years) were used to
      complete a Rasch analysis of the test. Seven items were discarded for poor fit,
      while none of the items exhibited differential item functioning by sex. The
      construct validity, scalability, hierarchical ordering, and lack of differential
      item functioning requirements were met by the final test version. Since 7 test
      items did not fit the Rasch analysis specifications, the clinical value of the
      test is questionable and limited.

PMID- 18712187
TI  - Effects of a computer-assisted language intervention in a rural Nevada center.
AB  - A computer-assisted language intervention, Fast ForWord-Language (FFW-L), was
      tested at a rural Nevada center in a group of children (Grades 2-12) referred by
      parents and teachers to assess enhancement of language skills. Given conflicting
      results from previous studies, language scores were measured using Clinical
      Evaluation of Language Fundamentals, Third Edition (CELF-3) before and after the
      FFW-L intervention. 58 children's CELF-3 postintervention scores were adjusted
      for age-specific expected changes and compared with pretest scores. Adjusted
      scores increased in both receptive and expressive domains of the CELF-3. Children
      with prior diagnoses of language and/or learning impairment did not differ from
      other referrals on adjusted CELF-3 adjusted gain scores after treatment. Thus the
      Fast ForWord-Language intervention may benefit a much broader group of children
      referred by parents and teachers for language or reading problems.

PMID- 18712188
TI  - Snoring, breathing pauses, and nightmares.
AB  - The present study investigated the correlations among snoring, breathing pauses
      during sleep, and nightmare frequency in a sample of 444 healthy individuals.
      Breathing pauses, but not snoring, were associated with heightened nightmare
      frequency. Whereas the hypothesis that shortage of oxygen directly causes
      nightmares is not supported by the literature, novel internal stimuli might
      affect dream content.

PMID- 18712189
TI  - Relation of dispositional optimism with burnout among athletes.
AB  - Optimism is important in enhancing human psychological and physical well-being;
      however, the association of optimism with burnout has received little attention
      in sport psychology. This study recruited 139 young volleyball players (M = 16.3
      yr., SD = 0.8) to examine this relation. Athletes completed the Chinese version
      of the Life Orientation Test at Time 1 and 4 mo. later (Time 2). The Chinese
      version of the Athlete Burnout Questionnaire was also administered. Analysis
      showed scores on optimism were negatively related to athletes' burnout scores.

PMID- 18712190
TI  - Dream recall frequency in a representative German sample.
AB  - The present study investigated the effects of sociodemographic variables on dream
      recall frequencies in a representative sample of 931 persons over 14 years of
      age. Analyses indicated that age, sex, and the size of the place of residence had
      small but significant effects: women and inhabitants of large cities tend to
      report dreams more often than men and residents of small towns. There was also a
      decline in dream-recall frequency with age. The explained variance, however, was
      small.

PMID- 18712191
TI  - Experience with a computer word-entry method in processing Chinese characters by
      fluent typists.
AB  - A 2003 study by Green and Bavelier showed that action video-game playing modified
      the visual selective attention of habitual players so the present hypothesis was
      whether processing of Chinese characters became more phonologically or
      orthographically oriented depending on whether participants were experienced
      typing with the phonological (zhuyin) or the orthographic (changjie) word-entry
      method. In Exp. 1, 38 changjie and 40 zhuyin users typed a short text on a
      computer using the word-entry method they had experienced. Every keystroke was
      recorded, and typing errors were categorized. In Exp. 2, 25 changjie and 25
      zhuyin users had to circle all characters which contained a predesignated radical
      when they read a short passage. In Exp. 3, 25 changjie and 20 zhuyin users heard
      pairs of syllables and had to decide whether the two syllables in a pair shared
      the same onset consonant in one block of trials or the same rhyme in another
      block of trials. Analysis showed participants with extensive experience using
      phonological typing displayed more phonologically related typing errors, better
      sensitivity to the onset and rhyme of a syllable, but poorer sensitivity to the
      radical of a character. Participants with extensive experience using orthographic
      typing displayed opposite results. Although the general cognitive system might be
      similar in the two groups of participants, the specific configuration of the
      system can vary to meet the demand of a particular design of the artifactual
      environment.

PMID- 18712192
TI  - Fixation identification in centroid versus start-point modes using eye-tracking
      data.
AB  - Fixation-identification algorithms, needed for analyses of eye movements, may
      typically be separated into three categories, viz. (i) velocity-based algorithms,
      (ii) area-based algorithms, and (iii) dispersion-based algorithms. Dispersion
      based algorithms are commonly used but this application introduces some
      difficulties, one being optimization. Basically, there are two modes to reach
      this goal of optimization, viz., the start-point mode and the centroid mode. The
      aim of the present study was to compare and evaluate these two dispersion-based
      algorithms. Manual inspections were made of 1,400 fixations in each mode. Odds
      ratios showed that by using the centroid mode for fixation detection, a valid
      fixation is 2.86 times more likely to be identified than by using the start-point
      mode. Moreover, the algorithm based on centroid mode dispersion showed a good
      interpretation speed, accuracy, robustness, and ease of implementation, as well
      as adequate parameter settings.

PMID- 18712193
TI  - Assessing executive functions in traumatic brain injury: an exploratory study of
      the Executive Interview.
AB  - Executive dysfunction is a frequent sequela of traumatic brain injury. Two
      correlational studies using samples of inpatients and outpatients diagnosed with
      traumatic brain injury were undertaken to evaluate the validity of a bedside
      screening test of executive functioning, the 1992 Executive Interview EXIT 25 by
      Royall, Mahurin, and Gray. In the first study of 23 inpatients receiving
      rehabilitation, the EXIT 25 was strongly related to both the Mini-Mental State
      Examination and the Modified Mini-Mental State Examination. In the second study
      of 20 outpatients, the EXIT 25 correlated with other executive function measures
      and with ratings of functional disability at discharge, although a ceiling effect
      raised questions about its utility for patients with mild to moderate disability.
      Further study of the EXIT 25 is justified with a larger sample of inpatients,
      although caution should be exercised when using the EXIT 25 in mildly impaired
      outpatients.

PMID- 18712194
TI  - Attractiveness of blonde women in evolutionary perspective: studies with two
      Polish samples.
AB  - An experimental study was undertaken to assess the phenomenon of male preference
      for blondes. In the first study, 360 Polish men ages 18 to 46 years were asked to
      assess the attractiveness of the presented stimuli using a 9-point scale. Stimuli
      were 9 different pictures of the same women whose ages (about 20, 30, and 40
      years old) and hair colors (blonde, brown, and brunette) were manipulated.
      Pictures of blonde-haired women were generally rated as younger than the others.
      The attractiveness ratings of female faces changed with age and hair color.
      Still, only the 30-yr.-old woman with blonde hair was rated as significantly more
      attractive than those with brown or brunette hair. In a second study (the
      analysis of 500 Internet advertisements) mature women dyed their hair blonde more
      frequently. These results are analyzed with regard to the evolutionarily formed
      male preference for younger females.

PMID- 18712195
TI  - Effect of a 9-wk. after-school multiskills club on fundamental movement skill
      proficiency in 8- to 9-yr.-old children: an exploratory trial.
AB  - This exploratory study examined the effects of a 9-wk. after-school multiskills
      club on fundamental movement skill proficiency in 8- to 9-yr.-old children. Two
      schools were randomly assigned to either a control (n = 15 children) or
      multiskill club (n = 19 children) condition. The multiskill club received 18
      coaching sessions designed to improve fundamental movement skills. The control
      group followed normal routines. 7 skills were assessed using process-oriented
      measures with video analysis. Participation in the multiskill club yielded
      significant improvements in proficiency at posttest only in static balance, while
      potentially practically important improvements were observed in performance of
      the catch, throw, and kick skills. The after-school multiskill club offered a
      viable opportunity for movement skill acquisition, but any such programme would
      need to run for a longer duration to assess whether this type of activity could
      benefit all skills.

PMID- 18712196
TI  - Effects of luminance ratio in a liquid-crystal display on discrimination of
      separation by elderly people.
AB  - In a 2006 study the influence of spacing between vertical lines, exposure time,
      and number of vertical lines on visual performance was identified. The present
      study further explored the effects of luminance ratio on discrimination of
      separation. Analysis showed the luminance ratio of target vertical lines affected
      the visual performance of both younger and elderly people. The luminance ratio
      was greater, as was accuracy; however, accuracy might not become greater when the
      luminance ratio was too high. Further, the effect of the number of vertical lines
      on accuracy was significant, as was consistent with the 2006 study. Two
      interactive two-way effects were found, group x luminance ratio and luminance
      ratio x number of vertical lines.

PMID- 18712197
TI  - Sensitive and tolerant raters differ in their magnitude estimates of extremely
      violent behaviors.
AB  - A 2007 study indicated severity of violence of several behaviors can be rated
      consistently, such that an individual's average rating across the behaviors can
      serve as a measure of sensitivity to violence. However, violence-sensitive and
      violence-tolerant raters in that study gave similar high scale ratings of
      severity of violence for extremely violent behaviors such as murder and stabbing.
      In the present study an open-ended magnitude estimation response scale was used
      by 27 participants to examine impressions of the severity of violence of 38
      behaviors. There was a positive correlation between estimates of severity for
      extreme physical violence and estimates for lower severity of violence. This
      result indicates that the earlier finding of apparent equivalence of sensitive
      and tolerant individuals did not signify agreement about extremely violent
      behaviors but was a ceiling effect arising from the closed-ended response scale
      used. Violence-sensitive and violence-tolerant individuals seem to have different
      attitudes toward all types of violence.

PMID- 18712198
TI  - Unidirectional interference in use of nondominant hand during concurrent Grooved
      Pegboard and random number generation tasks.
AB  - The interference effect between Grooved Pegboard task with either hand and the
      executive task of cued verbal random number generation was investigated. 24
      normal right-handed subjects performed each task under separate (single-task) and
      concurrent (dual-task) conditions. Articulatory suppression was required as an
      additional secondary task during pegboard performance. Analysis indicated an
      unambiguous distinction between the two hands. Comparisons of single-task and
      dual-task conditions showed an asymmetrical pattern of unidirectional
      interference with no practice effects during pegboard performance. Concurrent
      performance with nondominant hand but not the dominant hand of random number
      generation performance became continuously slower. There was no effect of divided
      attention on pegboard performance. Findings support the idea that the nondominant
      hand on the pegboard and random number tasks draw from the same processing
      resources but that for the executive aspect random number generation is more
      sensitive to changes in allocation of attentional resources.

PMID- 18712199
TI  - Effects of a physical education program on children's attitudes and emotions
      associated with sport climbing.
AB  - This study examined the effects of climbing ladders, wall bars, perches, and
      ropes in changing students' attitudes and emotions associated with sport
      climbing. The tasks were part of a physical education instructional curriculum of
      primary schools in Italy. Boys and girls (N = 80), ages 10 to 11 years, were
      involved in a 10-lesson intervention during their curricular lesson. Participants
      were from six normal classes ranging in size from 16 to 18 children. Three
      classes were assigned randomly to an experimental group and the other three to a
      control group. The experimental group performed challenging climbing tasks, while
      the control group engaged in other physical activities. Analysis of variance
      indicated that scores on the Climbing Pictures Test differed significantly after
      the intervention, with children in the experimental group scoring lower on
      avoidance of climbing situations and higher on positive emotions.

PMID- 18712200
TI  - Provisional norms by age group for Japanese females on the controlled force
      exertion test using a bar-chart display.
AB  - This study examined age-group and individual differences on the controlled force
      exertion test by bar-chart display and proposed a provisional norm in 249 females
      who were right-handed and ages 15 to 84 years. The subjects matched their
      submaximal grip strength to changing demand values, appearing as a bar chart on
      the display of a personal computer. The subjects performed the controlled force
      exertion test three times with 1-min. intervals (single trials were 40 sec.),
      after one practice trial using the dominant hand. A total of the differences (%)
      between the demand value and the grip-exertion value for 25 sec. was used as an
      evaluation parameter. The measurements showed a right-skewed distribution,
      normalized after logarithmic transformation. Analysis of variance identified
      significant differences between means of each age group; test performance
      decreased after 40 years of age. Norms for each age group were presented.

PMID- 18712201
TI  - Enumeration produces poor primacy for tactile presentation relative to visual and
      auditory presentation as the only modality effect.
AB  - Methodological biases may help explain the modality effect, which is superior
      recall of auditory recency (end of list) items relative to visual recency items.
      In 1985 Nairne and McNabb used a counting procedure to reduce methodological
      biases, and they produced modality-like effects, such that recall of tactile
      recency items was superior to recall of visual recency items. The present study
      extended Nairne and McNabb's counting procedure and controlled several variables
      which may have enhanced recall of tactile end items or disrupted recall of visual
      end items in their study. Although the results of the present study indicated
      general serial position effects across tactile, visual, and auditory presentation
      modalities, the tactile condition showed lower recall for the initial items in
      the presentation list than the other two conditions. Moreover, recall of the
      final list item did not differ across the three presentation modalities; modality
      effects were not found. These results did not replicate the findings of Nairne
      and McNabb, or much of the past research showing superior recall of auditory
      recency items. Implications of these findings are discussed.

PMID- 18712202
TI  - Relation of perfectionism with athletes' burnout: further examination.
AB  - The purpose was to examine the different aspects of perfectionism and athletes'
      burnout. College athletes (N = 320) with mean age of 19.7 yr. (SD = 1.4)
      completed the Chinese version of the Multiple Perfectionism Scale for Sport and
      the Eades' Athlete Burnout Inventory. Results indicated that perfectionism could
      be separated into adaptive and maladaptive perfectionism. Adaptive perfectionism
      was linked to reduced athletes' burnout while maladaptive perfectionism was
      associated with athletes' burnout. In addition, significant interaction was found
      between adaptive perfec tionism and maladaptive perfectionism on athletes'
      burnout. Results suggest that high maladaptive perfectionism and low adaptive
      perfectionism corresponds to higher scores on athletes' burnout. Perfectionism
      should not be treated as an all-or-nothing disposition. The extent of athlete
      burnout can vary with the interaction effects of the two types of perfectionism.
      In terms of practical implications in intervention work, coaches and sport
      psychologists should try to reduce athletes' maladaptive perfectionism and
      increase adaptive perfectionism.

PMID- 18712203
TI  - Oral cavity awareness in nonnative speakers acquiring English.
AB  - This investigation assessed awareness of the oral cavity of nonnative speakers
      acquiring English. University students (60 men, 60 women) were placed into three
      equal-size groups. The Less Experienced group lived in the USA less than 6 mo. (M
      = 3.3 mo., SD = 2.4). The More Experienced group lived in the United States 3 or
      more years (M = 5.0 yr., SD = 1.9). Native English speakers were the control
      group. Participants were recruited from undergraduate general education classes
      and passed a speech screening in English including accurate production of the
      seven English syllables tested, namely, suh, luh, tuh, kuh, ruh, shuh, and thuh.
      Participants answered four multiple-choice questions about lingual contact for
      each of the syllables imitated. Total test mean scores were significantly higher
      for the More Experienced group. Native speakers performed the task best. Findings
      support the effects of amount of time speaking the language. Training methods
      employed to teach English and slight dialectal variations may account for the
      significant differences seen in the two groups of nonnative speakers. Further
      study is warranted.

PMID- 18712204
TI  - Utility of habituation-dishabituation procedure for comparative cognitive studies
      of Callithrix jacchus and Aotus spp.: preliminary assessments.
AB  - The utility of the habituation-dishabituation procedure was examined in the
      common marmosets (Callithrix jacchus) and the owl monkeys (Aotus spp.). The same
      movies were repeatedly shown to monkeys during an habituation phase, followed by
      a test phase during which monkeys were presented with a different movie. The time
      monkeys spent looking at the movie gradually decreased during the habituation
      phase and then significantly increased when they were presented the new movie.
      The limited findings indicate that these monkeys were sensitive to the
      habituation-dishabituation paradigm, suggesting that this procedure might be used
      to assess cognition and perception.

PMID- 18712205
TI  - Eating behaviour, body image, and self-esteem of adolescent girls in Malaysia.
AB  - This cross-sectional study was undertaken with 489 secondary school girls, ages
      15-17 years, to examine disordered eating behaviours of adolescent girls in
      Malaysia and to estimate associations with body weight, body-size discrepancy,
      and self-esteem. Dietary restraint, binge eating, body image, and self-esteem
      were assessed using the Restrained Eating scale of the Dutch Eating Behaviour
      Questionnaire, the Binge Scale Questionnaire, the Contour Drawing Rating Scale,
      and the Rosenberg Self-Esteem Scale, respectively. Pearson correlations estimated
      associations between variables. There were 3.1% underweight, 9.8% at risk of
      being overweight, and 8.6% overweight girls. A total of 87.3% were dissatisfied
      with their own body size. Dietary restraint and binge eating were reported by
      36.0% and 35.4%, respectively. Body Mass Index (r = .34, p < .01) and body-size
      dissatisfaction (r = .24, p < .01) were significantly associated with dietary
      restraint and binge eating, but self-esteem (r = -.20, p < .001) was
      significantly associated only with binge eating.

PMID- 18712206
TI  - Experimental note on fading of briefly flashed lines.
AB  - A peripheral uniform stimulus on a uniform background tends to fade when a ring
      enclosing the stimulus is flashed briefly, indicating that neural signals
      external to the stimulus such as those from the ring or those from the background
      tend to inhibit the onset-response or after-discharge of the stimulus. In this
      study, a peripheral achromatic line was flashed briefly on an achromatic
      background while the subject was steadily fixating on a point on the background.
      It was predicted that the stimulus line would fade due to background inhibition
      of the onset-response or afterdischarge of the stimulus. On a reference line,
      subjects indicated two points delimiting the part of the stimulus line which
      looked uniform in intensity of color. These points converged toward the center of
      the reference line as the luminance of the stimulus line approached that of the
      background. Compared to the central uniform part, the nonuniform parts near the
      endpoints of the stimulus line looked more faded. These results support the idea
      that the background surrounding a stimulus tends to inhibit the onset-response of
      after-discharge of the stimulus.

PMID- 18712207
TI  - Person-centered support and athletes' motivation for performance.
AB  - The purpose of the study was to examine the effect of person-centered
      intervention on motivation for athletic performance. 74 volleyball players, 24
      boys and 50 girls (M age = 13 yr., SD = 1.0), completed a motivation
      questionnaire, the Leistungs Motivations Test fur Jugendlichen prior to and after
      an 8-mo. group treatment that included the application of Roger's person-centered
      method to the participants of the experimental group (1 boys' team n = 12; 1
      girls' team n = 11), at a frequency of at least one session per week. In the
      control group (1 boys' team n = 12; 3 girls' teams n = 39), no particular method
      was used apart from the pedagogical methods that coaches selected. Results
      revealed a statistically significant decrease in boys' scores on desire for
      performance and success between the pre- and posttest measurements. No
      significant change in girls' scores was observed. Thus, the 8-mo. treatment using
      the person-centered method did not improve volleyball players' motivation for
      performance.

PMID- 18712208
TI  - Technical variation in a sample of high level judo players.
AB  - Technical actions performed by two groups of judokas who won medals at World
      Championships and Olympic Games during the period 1995-2001 were analyzed. In the
      Super Elite group (n = 17) were the best athletes in each weight category. The
      Elite group (n = 16) were medal winners who were not champions and did not win
      more than three medals. Super Elite judokas used a greater number of throwing
      techniques which resulted in scores, even when expressed relative to the total
      number of matches performed, and these techniques were applied in more directions
      than those of Elite judokas. Further, the number of different throwing techniques
      and the variability of directions in which techniques were applied were
      significantly correlated with number of wins and the number of points and ippon
      scored. Thus, a greater number of throwing techniques and use of directions for
      attack seem to be important in increasing unpredictability during judo matches.

PMID- 18712209
TI  - Oral perception of bolus in healthy young women.
AB  - This study was designed to characterize oral perception of both weight and volume
      of boluses. A total of 80 healthy young female subjects was recruited and divided
      into bolus weight (n = 40) and bolus volume (n = 40) conditions. Tap water (25
      degrees C) was the experimental material, and seven reference stimulus amounts
      ranging from 10 to 40 (grams and mL) were prepared. The reference stimuli,
      including a modulus of 20 (grams and mL), were delivered to the subjects in
      randomized order. The estimated magnitudes (psi) conformed to both the Fechner's
      and Stevens' psychophysical laws by the following equations: (1) psi(W) = 314.3
      log (S+1) - 300.2 where S is stimulus intensity or weight, and psi(V) = 249.7 log
      (S+1) - 222.3 (volume) on logarithmic (log)-linear scales, and (2) psi(W) = 1.908
      S1.297 and psi(V) = 4.097 S1.032 on log-log scales, respectively. The results
      indicate that oral perception of bolus weight and bolus volume conforms to the
      representative psychophysical laws.

PMID- 18712210
TI  - The International Wayfinding Strategy Scale: evidence for cross-cultural use with
      a sample from the UK.
AB  - This study suggested Lawton and Kallai's 2002 International Wayfinding Strategy
      Scale was appropriate for use in the UK. Participants at a northeastern English
      university (N = 148) completed the scale. Principal components analysis (oblimin
      rotation) with 2 factors specified supported the expected structure and indicated
      the scale could be used to measure wayfinding strategies across cultures;
      however, 1 of the 17 original items on the scale was not suitable for use with a
      UK sample and 1 item loaded on the opposite factor as expected. The resulting
      orientation strategy score was used more by men, but the mean route strategy
      scale scores did not differ by sex.

PMID- 18712211
TI  - Digit ratio (2D:4D) and wearing of wedding rings.
AB  - Digit ratio (2D:4D), a putative marker for prenatal androgen levels, and absolute
      finger length, a marker for pubertal androgen action, were not associated with
      wearing of wedding rings in a sample of 150 male and 199 female married
      individuals. This failure to replicate associations previously reported by
      Manning was true for both men and women, self-reported and spousal ring-wearing
      behavior, and one's own and spousal 2D:4D or absolute finger lengths.
      Supplemental findings included sex differences and age effects in the prevalence
      of wearing wedding rings (more frequent in women and the younger than in men and
      the older) and a sex bias when ring-wearing behavior within couples was
      discordant (men more frequently did not wear their wedding ring when their wives
      did than vice versa). Discussed are implications of the current findings and
      directions for future research into possible associations of 2D:4D with other
      aspects of body ornamentation.

PMID- 18712212
TI  - Response to Brasic (2007): psychomotor study of children with ADHD.
AB  - In 2007 Brasic questioned the methodology used by Pedersen and Surburg to test
      the effect of stimulant medication on lower extremity motor processing of
      children with attention deficit hyperactivity disorder (ADHD). The purpose of
      this response is to clarify the research design used in that 2005 study.

PMID- 18712213
TI  - RPE at relative intensities after 12 weeks of resistance-exercise training by
      older adults.
AB  - The constant-RPE tracking model monitors progress over the course of exercise
      training. During aerobic exercise, prior work using this model has demonstrated
      similar relative intensities pre- and posttraining, while the absolute workload
      increases posttraining. However, the prediction equation associated with these
      changes has not been examined during resistance training. 22 men and 27 women (M
      age 64 yr.) participated in a 12-wk. resistance training. Orientation determined
      resistances associated with RPEs of 4, 5-6, 7-8, and 9 on the OMNI-Resistance
      Exercise Scale for each of seven exercises for each participant. Individuals
      trained 3 days a week for 12 wk. Linear regression was used to calculate percent
      of 1-repetition maximum (%1-RM) at RPE 4, 6, and 8 for the exercises. Paired
      sample t tests, comparing pre- and posttraining %1-RMs at each RPE, indicated
      that posttraining %1-RMs were higher for RPE 4 and 6 for each exercise, while at
      RPE 8, results were significant for only 3 exercises. Thus for at least the RPE 4
      and 6, the constant RPE tracking model is appropriate for resistance exercise;
      however, the equation of prediction appears to differ from that for aerobic
      exercise. Development of a new prediction equation may be necessary to track
      relative strength in older adults.

PMID- 18712214
TI  - Monitoring changes in rugby league players' perceived stress and recovery during
      intensified training.
AB  - This study assessed whether the Recovery-Stress Questionnaire for Athletes (RESTQ
      Sport) could be used to monitor changes in perceived stress and recovery during
      intensified training of rugby league players. 20 semiprofessional rugby league
      players were divided into two equal groups randomly assigned to complete 6 wk. of
      Normal Training or Intensified Training, each followed with a 7-day taper.
      Multistage Fitness Test performance and RESTQ-Sport measures were taken at the
      beginning, at 2-wk. intervals, and at the end of the training period. Endurance
      significantly decreased with Intensified Training and returned to baseline levels
      following the taper, while remaining unchanged in the Normal Training group. The
      RESTQ-Sport scores with training were positively related to stress subscale
      scores (Fatigue, Disturbed Breaks, and General Stress) and recovery subscale
      measures (Success, Physical Recovery, Being in Shape, Self-efficacy, Social
      Relaxation, General Well-being, and Sleep Quality) decreasing in the Intensified
      Training group and then normalising following the taper (Stress subscales:
      Fatigue and General Stress, and Recovery subscales: Physical Recovery and General
      Well-being). The RESTQ-Sport is a practical psychometric tool for monitoring
      responses to training in team-sport athletes.

PMID- 18712215
TI  - Abdominal exercise intensities on firm and compliant surfaces.
AB  - Muscle activities at 15 sites were compared within a group of healthy young
      adults to evaluate their relative intensities during six abdominal exercises:
      partial and full sit-ups on a firm surface (floor) and on an exercise ball that
      was either stabilized or unstabilized. The most strenuous abdominal exercise
      overall (i.e., whole body workout) was the full sit-up on a firm surface which
      included significant muscle activities in the lower extremities. Exercise
      intensity was also high in the full and partial sit-ups when performed on a ball.
      The partial sit-up on the floor was the least strenuous of the six exercises. The
      greatest effect on the abdominal muscles was observed in the partial sit-up on a
      ball (stabilized and unstabilized). Results suggest that, although abdominal
      exercises on a ball may be gentler on the hip and lower back, overall exercise
      intensity is not necessarily lower than that on the floor. Moreover, partial sit
      ups, both on the floor and on a ball, also required greater neck muscle
      activities than full sit-ups. In deciding what type of sit-up to do, exercise
      surface and different muscular activities between the partial and full sit-ups
      should be considered.

PMID- 18712216
TI  - Effects of music on memory for text.
AB  - Previous research has suggested that the use of song can facilitate recall of
      text. This study examined the effect of repetition of a melody across verses,
      familiarity with the melody, rhythm, and other structural processing hypotheses
      to explain this phenomenon. Two experiments were conducted, each with 100
      participants recruited from undergraduate Psychology programs (44 men, 156 women,
      M age = 28.5 yr., SD = 9.4). In Exp. 1, participants learned a four-verse ballad
      in one of five encoding conditions (familiar melody, unfamiliar melody, unknown
      rhythm, known rhythm, and spoken). Exp. 2 assessed the effect of familiarity in
      rhythm-only conditions and of pre-exposure with a previously unfamiliar melody.
      Measures taken were number of verbatim words recalled and number of lines
      produced with correct syllabic structure. Analysis indicated that rhythm, with or
      without musical accompaniment, can facilitate recall of text, suggesting that
      rhythm may provide a schematic frame to which text can be attached. Similarly,
      familiarity with the rhythm or melody facilitated recall. Findings are discussed
      in terms of integration and dual-processing theories.

PMID- 18712217
TI  - The effect of light color on muscular strength and power.
AB  - The purpose of this study was to assess the effect of the color of light in a
      room on muscular strength and power. A convenience sample of 18 men (M age = 20.4
      yr., SD = 1.2) performed a modified Wingate Anaerobic Cycle Test for muscular
      power and a hand grip strength test in each of the following conditions: red,
      blue, and white (neutral) ambient light. A repeated-measures multivariate
      analysis of variance indicated that average muscular power was significantly
      higher when performing the test in the room with red light compared to rooms lit
      with blue light or white light. The results also indicated that grip strength was
      significantly higher in the room lit with white light as compared to the room lit
      with blue light.

PMID- 18712218
TI  - Relationship between upper extremity kinesthetic sense and writing performance by
      students with low vision.
AB  - Kinesthetic sense plays an important role in writing. Children with low vision
      lack sensory input from the environment given their loss of vision. This study
      assessed the effect of upper extremity kinesthetic sense on writing function in
      two groups, one of students with low vision (9 girls and 11 boys, 9.4 +/- 1.9 yr.
      of age) and one of sighted students (10 girls and 10 boys, 10.1 +/- 1.3 yr. of
      age). All participants were given the Kinesthesia Test and Jebsen Hand Function
      Test-Writing subtest. Students with low vision scored lower on kinesthetic
      perception and writing performance than sighted peers. The correlation between
      scores for writing performance and upper extremity kinesthetic sense in the two
      groups was significant (r = -.34). The probability of deficiencies in kinesthetic
      information in students with low vision must be remembered.

PMID- 18712219
TI  - Rehearsal strategies during motor-sequence learning in old age: execution vs
      motor imagery.
AB  - Motor imagery and action-based rehearsal were compared during motor sequence
      learning by young adults (M = 25 yr., SD = 3) and aged adults (M = 63 yr., SD =
      7). General accuracy of aged adults was lower than that of young adults (F(1,28)
      = 7.37, p =.01) even though working-memory capacity was equivalent in the two
      groups. Motor imagery and rehearsal by action increased accuracy in both age
      groups, compared with minimization of opportunity for rehearsal (F(1,28) = 30.95,
      p < .001), but no interaction was found with age group, which suggests that young
      and aged adults were equally capable of motor imagery and action-based rehearsal.
      It was assumed that differences in performance between young and aged
      participants related to the formation of mental representations of sequences and
      integration of new elements into these representations rather than the capacity
      for motor imagery or rehearsal by action per se. The current study was
      exploratory and involved a relatively small sample of 15 participants per age
      group. Caution must be taken when considering the results.

PMID- 18712220
TI  - [Dissection of the carotid artery following blunt trauma: still a pitfall].
AB  - Two young patients, an 18-year-old woman and a 25-year-old man, were admitted to
      hospital after accidents with a car. They developed very severe complications as
      a consequence of blunt carotid artery dissection. This diagnosis was delayed in
      both patients until serious cerebral ischaemia had occurred. Despite current
      awareness of carotid dissection as a possible result of blunt trauma, this injury
      is often overlooked. Early diagnosis by means of Doppler ultrasonography and CT
      angiography is important in adequate management of this injury and may reduce
      morbidity and mortality. The treatment of carotid dissection consists of
      antithrombotic, endovascular or surgical therapy and needs to be individualized.

PMID- 18712221
TI  - [American judge preserves confidentiality in the peer review process].
AB  - Pharmaceutical concern Pfizer subpoenaed various medical journals, including JAMA
      and Annals of Internal Medicine, to hand over confidential documents relating to
      studies on its cyclo-oxygenase-2 inhibitors celecoxib and valdecoxib. Pfizer
      wanted this information to help defend 3000 product liability lawsuits over
      alleged side effects of the 2 drugs. However, a federal judge in Chicago rejected
      the company's bid, thereby preserving the confidentiality of the peer review
      process. It is unlikely that subpoenas like this will take place in the
      Netherlands.

PMID- 18712222
TI  - [Walking in the International Four Days Marches Nijmegen: an estimation of the
      risks].
AB  - In 2006, the annual Four Days Marches in Nijmegen, the Netherlands, were
      cancelled after the first day because two participants had died, and many had
      become unwell while walking in unusually high ambient temperatures. During the
      2007 edition, an observational study of the physiological impact and health risks
      for walkers was carried out. This time, the ambient conditions were mild. Most
      participants (90.7%) finished the march without serious complaints or clinical
      complications, despite significant disturbances in fluid balance and
      electrolytes. The training level of the participants varied considerably. If we
      compare the results of this physiological study with studies during marathons,
      similarities in physiological adaptions are found, most probably due to the same
      biological mechanisms. However, the participants of the Four Days Marches are
      incomparable with long-distance runners. There is as yet no well-founded advice
      concerning the fluid intake of Four Days Marches participants. Increase or
      decrease in body weight may be an interesting diagnostic tool to measure the risk
      of dehydration or overhydration.

PMID- 18712223
TI  - [Clinical reasoning and decision-making in practice. A man with hip pain and
      fever].
AB  - A 42-year-old man was admitted to the hospital because of pain in the left hip.
      On examination he was febrile at 38 degrees C and he walked with a limp. The
      chest, abdomen and extremities were normal. Laboratory tests showed an elevated
      ESR and CRP. The ANA test was positive. CT-scan of the abdomen revealed a mass in
      the psoas region and some dilatation of the left renal pelvis. Following the
      histological results of the first and second diagnostic percutaneous biopsies,
      the clinicians suspected idiopathic retroperitoneal fibrosis. They treated the
      patient with corticosteroids for a period of 4 weeks. After a short interval of
      improvement this treatment failed and a third biopsy was taken. Subsequently, the
      diagnosis of anaplastic large cell lymphoma (ALCL) was made. The patient was
      successfully treated with combination chemotherapy. Usually, in practice,
      clinical reasoning and decision-making is carried out in accordance with Bayes'
      theorem. But when the a priori probability of disease is unknown and the
      likelihood ratio of a diagnostic test unavailable, one has to combine the
      available 'evidence' with critical thinking, interdisciplinary communication,
      judgement, intuition and common sense.

PMID- 18712224
TI  - [Folic acid fortification of bread recommendable].
AB  - Folic acid supplementation was recommended in the Netherlands after it had been
      demonstrated that periconceptional use of folic acid protected against foetal
      neural tube defects; this recommendation led to a slight decrease in prevalence
      only. According to the Dutch Health Council, fortification of bread should now be
      considered. Policy-making is complicated by uncertainties regarding potential
      side effects, such as adverse effects in children, for which scientific evidence
      is lacking however.

PMID- 18712225
TI  - [Folic acid should not be added automatically to bread].
AB  - The Health Council of the Netherlands recommends fortifying bread with folic acid
      to ensure that women have a basic level of folic acid intake around the time of
      conception in order to prevent neonatal neural tube defects. This advice should
      not be followed because Dutch children who already have adequate intake may
      easily be overdosed. Sixteen million people will be subjected to lifelong folic
      acid intake to prevent neural tube defects in 30 of the 200,000 babies born each
      year. A long-term investment in education and care targeting immigrant women is a
      much more effective and efficient alternative.

PMID- 18712226
TI  - [Diagnostic image (380). A woman with papules on the heel].
AB  - A 54-year-old woman had piezogenic pedal papules. They became apparent when she
      was standing, and disappeared when the weight was taken off the foot.

PMID- 18712227
TI  - [Physical risks whilst walking the Nijmegen Four Days Marches in 2007:
      electrolyte imbalance in 1 in 5 walkers].
AB  - OBJECTIVE: To determine the physiological impact and health risks for walkers
      during the Nijmegen (the Netherlands) Four Days Marches in 2007, the largest
      walking event in the world with more than 45,000 participants. DESIGN:
      Observational study. METHODS: 66 volunteers were randomly selected and
      counterbalanced for distance walked and gender in this observational study.
      Subjects walked 30 km (n = 20; 10 men), 40 km (n = 25; 14 men) or 50 km (n = 21;
      10 men) per day, for 4 consecutive days. Core body temperature, fluid intake,
      changes in body weight, plasma sodium concentrations and energy usage were
      measured before and after the marches. RESULTS: During this event, ambient
      temperatures ranged from 11.0 degrees C to a maximum 25.4 degrees C expressed as
      'wet bulb globe temperature' (WBGT). Heart rate (+38 beats per minute) and core
      body temperature (+0.8 degree C) significantly increased in all subjects during
      each day (about 9 hours walking per day at an average of 4.6 km/h), but
      hyperthermia was not diagnosed (definition: > 39.0 degrees C). Average fluid
      intake varied between 2.6 and 3.3 l/d with a range of 0.3-12 l/d. The relative
      change in body weight associated with this was -3.1 to +4.3%. Mean plasma sodium
      concentration decreased from 142.4 to 140.6 mmol/l over each walking day. The
      plasma sodium correlated negatively with fluid intake (r = -0.32; p < o.001),
      change in body weight (r = -0.13; p < 0.05), and walking time (r = -0.37; p <
      0.001). A high prevalence of hyponatraemia (5%) and hypernatraemia (16%) was
      observed; extrapolating these findings to the entire field a large group (about
      10,000) would have been at risk with this electrolyte imbalance. CONCLUSION: This
      study showed that walking the Four Days Marches in Nijmegen with mild ambient
      conditions led to one in five participants incurring disturbances in fluid and
      electrolyte balance. Nonetheless, the participants were well able to keep their
      increasing core temperature within safe limits. Apart from the frequent
      electrolyte imbalance, the fluid intake varied strongly between individuals.

PMID- 18712228
TI  - [An aphasic man with high fever; difficulty with diagnostic procedure].
AB  - A 73-year-old man, with known motor aphasia presented with high fever, dyspnoea,
      and vomiting. Only after several days it appeared that these signs were due to a
      sepsis as a consequence of a phlegmon of the neck, caused by an aspired part of
      his set of false teeth. The delay before diagnosis was due to the fact that
      adequate medical history taking was difficult because of the aphasia and attempts
      at non-verbal communication were poorly understood. The localization of the
      corpus alienum was a second pitfall, because it could not be visualized during
      physical examination or on the initial chest X-ray. The increased risk of
      colonization of dentures with pathogenic micro-organisms in nursing home
      residents may have played a role in the severe course of this infection. This
      case illustrates the diagnostic problems that may exist in patients who are
      unable to communicate adequately.

PMID- 18712229
TI  - [Acute caffeine intoxication after intake of 'herbal energy capsules'].
AB  - Two males, 15 and 17 years old respectively, presented at the Emergency
      Department complaining of cramping abdominal pain, nausea and vomiting after
      ingestion of energy capsules. Physical examination revealed sinus tachycardia and
      slight abdominal pain. Laboratory examination showed substantial hypokalaemia and
      mild hyperglycaemia. Questioning revealed that they had taken 5 and 3 'herbal
      energy capsules' respectively and that these capsules supposedly contained 200 mg
      of caffeine each. Toxicological analysis showed a greatly increased serum
      caffeine concentration in both patients. The peak concentrations calculated were
      in the highly toxic range and could have led to severe acute complications such
      as convulsions. Pharmaceutical analysis demonstrated that these 'Supercap Xtreme'
      capsules contained 700 mg caffeine or more. All symptoms presented were
      compatible with caffeine intoxication. The content of these capsules is not
      reliable and could lead to life-threatening intoxication.

PMID- 18712230
TI  - [Probiotic prophylaxis in patients with predicted severe acute pancreatitis: a
      randomised, double-blind, placebo-controlled trial and informed consent
      procedure].

PMID- 18712231
TI  - [Probiotic prophylaxis in patients with predicted severe acute pancreatitis: a
      randomised, double-blind, placebo-controlled trial and informed consent
      procedure].

PMID- 18712232
TI  - [Probiotic prophylaxis in patients with predicted severe acute pancreatitis: a
      randomised, double-blind, placebo-controlled trial and informed consent
      procedure].

PMID- 18712233
TI  - On delivering change.

PMID- 18712234
TI  - Improving end-of-life care.

PMID- 18712235
TI  - Saving lives step by step.

PMID- 18712236
TI  - Meet the English patient.
AB  - Hospital nurses in England are most likely to find that their typical patient is
      an older female. She will have been referred by her GP, with whom she is
      satisfied. Satisfaction with the NHS, however, is likely to reduce during her
      five-day stay. Even though her expectations are lower in hospital than they are
      when she is using primary care services, she is less likely to complain. She is
      more likely to respond negatively to surveys. Even so, she is likely to rate
      nurses highly.

PMID- 18712237
TI  - More than a nurse.
AB  - Patients pay tribute to nurses who have fulfilled their role with compassion and
      rigour.

PMID- 18712238
TI  - Taking complaints seriously.
AB  - Even the best homes may sometimes come into conflict with relatives. Would an
      independent complaints procedure help?

PMID- 18712239
TI  - Listening to women's problems.
AB  - Women can receive conflicting and confusing information about their reproductive
      health. Women's Health Concern is there to help.

PMID- 18712240
TI  - Woman in black.

PMID- 18712241
TI  - Early, moderate and safe. Should parents introduce their children to alcohol at
      home, and encourage them to drink sensibly?

PMID- 18712242
TI  - Honour of carrying out last offices helped calm my nerves.

PMID- 18712243
TI  - Nursing care, education and support for patients with neutropenia.
AB  - Neutropenia is reduced white blood cell count. It is a side effect of cytotoxic
      chemotherapy for cancer and haematological patients. This article aims to help
      nursing students and qualified nurses who are novices in caring for neutropenic
      patients to become familiar with the usual body defences against infection;
      understand how the body's ability to fight infection is affected by neutropenia;
      recognise potential sources of infection; and support the patient who is at risk
      of infection as a result of neutropenia.

PMID- 18712244
TI  - Measuring compassion in nursing.
AB  - This article considers the implications of recent proposals to score nurses
      according to the level of compassion that they provide.

PMID- 18712245
TI  - Safe practice in intravenous medicines administration.
AB  - This article offers a practical guide on injecting medicines via the intravenous
      (IV) route, ensuring safe and effective practice. It considers the benefits of
      the IV route as well as possible hazards and complications. Through the
      assessment of risk, it outlines good practice standards.

PMID- 18712246
TI  - Identifying, reporting and preventing elder abuse in the practice setting.
AB  - The purpose of this article is to raise awareness of elder abuse as an issue and
      its changing policy and legislative context. It highlights nurses' roles and
      responsibilities, enabling the reader to explore the complexities that surround
      elder abuse as a phenomenon and recognise effective strategies for identifying,
      reporting and preventing elder abuse in the practice setting.

PMID- 18712247
TI  - Schizophrenia.

PMID- 18712248
TI  - International recognition.

PMID- 18712249
TI  - Positive partnerships.

PMID- 18712250
TI  - Feeling the squeeze.

PMID- 18712251
TI  - Why hospitals are becoming cleaner.

PMID- 18712252
TI  - 'Keeping older people from poverty is our duty'.

PMID- 18712253
TI  - Dilemma. Should hospitals inform parents when their teenager has terminated a
      pregnancy?

PMID- 18712254
TI  - Can the NHS ever be green?

PMID- 18712255
TI  - The lure of nursing in Alberta.

PMID- 18712256
TI  - Sickle cell disease standards tackle inequality in adult care.

PMID- 18712257
TI  - Neurological assessment part 3--Glasgow Coma Scale.

PMID- 18712258
TI  - Discharge after colorectal cancer surgery 2: planning.
AB  - This is a two-part unit on preparing patients for hospital discharge following
      surgery for colorectal cancer. Part 1 explored the rationale for different
      surgical procedures, and discussed common side-effects and the impact of
      treatment on patients. This second part addresses the various components of good
      discharge planning: assessment; technical care; coordination and communication;
      emotional support; the rehabilitation process; and family involvement (Long et
      al, 2002).

PMID- 18712259
TI  - 'We are running a massive drug trial on fat children'.

PMID- 18712260
TI  - [Zoonoses transmitted by mouse and rat maintained as laboratory or pet animals].
AB  - Large numbers of mice (Mus spp.) and rats (Rattus spp.) are maintained for
      scientific reasons and as pet animals in Germany. While laboratory animals are
      monitored for pathogenic agents, the hygienic status of pet animals is usually
      completely unknown. Despite great efforts, zoonotic infections were reported even
      in laboratory settings, e.g. with Hantavirus (Seoul virus), Streptobacillus
      moniliformis, and Trichphyton mentagrophytes. However, in current reports,
      zoonotic infections were transmitted by mice and rats maintained as pet animals.
      This includes infections by Lymphocytic choriomeningitis virus, Leptospira
      interrogans, Streptobacillus moniliformis, Salmonella enterica, Trichophyton
      mentagrophytes, and Ornithonyssus bacoti. Furthermore, entero-hepatic
      Helicobacter spp. of rats and mice are currently discussed to be involved in the
      etiology of hepatobiliary diseases. Pasteurella spp. of mice and rats do not
      present a risk for human disease comparable to those species that are transmitted
      by dogs or cats and might induce serious disease after bites. Altogether, this
      article lists potential zoonotic agents that were detected in mice and rats and
      are present in Germany, as well as agents that were reportedly transmitted by
      mice and rats maintained as laboratory or pet rodents.

PMID- 18712261
TI  - The role of dietary calcium concentration in the use of anionic salts to prevent
      parturient paresis in dairy cows.
AB  - The role of dietary calcium concentration during the feeding of anionic salts
      (AS) was reviewed. Hypocalcaemia is still the major cause of parturient paresis
      in dairy cows. Feeding AS is an established method for preventing severe
      hypocalcaemia by activating the calcium metabolism in the last two to three weeks
      before parturition by inducing a metabolic acidosis. In compensation for this
      acidosis, the organism increases the concentrations of ionised Ca [Ca2+] in the
      blood. This increase leads to an increasing excretion of calcium via the urine,
      which is ensued by an increased calcium absorption in the intestine. The ongoing
      metabolic acidosis changed the flux of Ca. The size of the Ca pool, however,
      remained unchanged. As the calcium metabolism is activated by AS, it seems
      necessary to increase the amount of calcium that is fed to the cows. Several
      studies examined the impact of different dietary calcium concentrations on the
      acid-base balance and the calcium metabolism in cows fed anionic salts. The study
      designs vary concerning the amounts of calcium fed and the use of pregnant or non
      pregnant cows. Only one study combined the feeding of AS with a very low amount
      of calcium, which fell below the daily requirements of pregnant cows in the last
      three weeks before parturition. In this study, the calcium balance post partum
      was better in the cows that were administered AS and a high calcium diet. In the
      other studies, the amount of calcium in the different experimental groups and the
      difference between the amounts of calcium fed varied greatly. As far as it was
      monitored in the studies, the calcium concentration of the diet did not have a
      significant impact on the degree of acidosis induced by AS. In pregnant cows, no
      significant differences in the calcium concentration in serum or urine occurred
      before parturition. Some of the researchers found a lower incidence of parturient
      paresis when cows were fed a combination of AS and a higher amount of calcium,
      but some other researches did not. Interestingly, the parameters of bone
      metabolism did not change between experimental groups. According to what is
      currently known, the feeding of AS to transition cows should not be combined with
      a dietary calcium concentration that falls below the requirement of cows in this
      stage of lactation. On the other hand, there is no need to increase the Ca
      concentration. When AS are used the dietary calcium concentration should be
      between 9 g and 12 g/kg dry matter. Further research is needed to investigate the
      role of dietary calcium regarding the use of AS for improving Ca metabolism in
      dairy cows around parturition.

PMID- 18712262
TI  - [Detection of bovine leukaemia virus (BLV) in tissue samples of naturally and
      experimentally infected cattle].
AB  - Enzootic bovine leukaemia (EBL) which is caused by the bovine leukaemia virus
      (BLV) still plays a remarkable role despite a significant success in sanitation
      programmes. In the Federal Republic of Germany it was not possible to eradicate
      the disease until today. Sporadically during slaughter or necropsy of cattle
      neoplastic lesions of the lymphatic tissues are observed that need to be
      clarified with regard to BLV as etiological agent. Due to the fact that in most
      instances no serological data are available from the respective animals and blood
      drawings from the original holdings are not easy to obtain the polymerase chain
      reaction (PCR) opens new avenues as supplementary diagnostic tool to test unfixed
      lymphatic tissues for the presence of BLV proviral DNA. Lymph node tissues from
      10 naturally or experimentally BLV-infected cattle, which have been monitored
      virologically and serologically, and tissues from 4 negative animals were
      processed, DNA was extracted and subjected to PCR to amplify BLV env gene
      specific sequences. The results show that in cattle with BLV-induced leukosis as
      well as in cattle, which were clinically healthy and unsuspicious at slaughter or
      at post-mortem, either with persistent lymphocytosis (PL) or without, BLV
      proviral DNA could be detected easily in samples of lymphatic tissues and in high
      concordance with serological data. In this article data from the National and OIE
      reference laboratory for EBL at the Friedrich-Loeffler-Institut (FLI, Germany)
      are presented. Elaborated laboratory protocols for processing of tissue samples
      and performing of BLV-PCR are recommended.

PMID- 18712263
TI  - [Mycobacterium gordonae as potential cause of granulomatous lesions of the toe
      tips in the South African clawed frog (Xenopus laevis)].
AB  - During regular health status monitoring of the colony of amphibian, Mycobacterium
      (M.) gordonae were isolated from granulomatous lesions of the tiptoes from the
      South African clawed frog (Xenopus laevis) maintained at the
      Tierforschungszentrum of the University of Ulm. During a period of three years a
      total of 21 animals of the colony, consisting of 350-400 frogs, showed granuloma
      of the tip of the toes and a loss of the claws. The general condition and the
      behavior of the frogs appeared to be unchanged. Using a selective medium one
      isolate was cultured and identified by sequencing of the 16S rRNA gene. To apply
      a rapid diagnostic method for detecting mycobacteria, in particular M. gordonae
      in the health monitoring programme of the Xenopus laevis colony, we established
      the rpoB gene PCR followed by HaeIII restriction analysis of the PCR product. We
      identified M. gordonae from granuloma of the tiptoes and from unaltered tissue
      samples of the lungs and skin by PCR restriction analysis. Since mycobacterial
      species apparently are widespread in granulomatous lesions of the tiptoes of
      Xenopus laevis, we hypothesize a pathogenic potential. This view is supported by
      an increasing number of reports in the literature on infections with
      nontuberculous, "non-pathogenic" mycobacteria in Xenopus laevis.

PMID- 18712264
TI  - [Influence of different copper and zinc supply on their concentrations in blood
      serum, liver and hair of dairy cows].
AB  - In a feeding trial at the Institute of Animal Nutrition of the Federal Research
      Institute of Animal Health (FLI) over 12 weeks with 20 cows of the German
      Holstein Breed the influence of different copper and zinc contents in the ration
      on their concentration in blood serum, liver and hair was tested. All animals
      received a diet based on maize- and grass silage ad libitum. The animals were
      divided in two groups with 10 cows each; group A received a concentrate according
      to their milk yield with a copper and zinc content as recommended (GfE 2001),
      whereas group B was offered a concentrate with roughly the double amount of
      copper and zinc. At the beginning and at the end of the trial a sample of blood,
      pigmented hair and a liver bioptate was taken from all animals to evaluate the
      incorporation of copper and zinc in these tissues. In serum and pigmented hair
      the copper concentrations did not differ between the two groups [13.4 for Group A
      and 12.5 micromol/L for Group B in serum respectively 6.8 (Group A) and 7.4 mg/kg
      DM (Group B) in pigmented hair]. Only the copper concentration in the liver was
      influenced by the different feeding. The higher copper content for group B
      resulted in a significantly higher copper concentration in the liver (506 mg/kg
      DM compared to 383 mg/kg DM). The liver is the best indicator organ for a
      sufficient copper supply. An increase in the zinc content in the ration resulted
      neither in higher zinc concentrations in serum (15.1 in Group B in comparison to
      13.4 micromol/L for Group A) nor in higher zinc concentrations in liver (140 for
      Group B and 112 mg/kg DM for Group A) and pigmented hair (130 in Group A and 123
      mg/kg DM in Group B). There is a significant correlation between copper intake
      and copper concentration in the liver (r = 0.46), whereas the correlation between
      zinc intake and zinc concentration in the liver is only tendencially (r = 0.23).
      The three tested samples serum, liver and cow hair are not qualified to reflect
      exactly a sufficient zinc supply.

PMID- 18712265
TI  - Analysis of systematic and genetic effects on the prevalence of different types
      of primary lens opacifications in the wild-boar-colored wirehaired Dachshund.
AB  - The aims of this study were to analyze the influence of systematic environmental
      effects on the prevalence of primary non-congenital cataract (CAT), fibreglass
      cataract in the nucleus (FCN), and prominent suture lines (PSL) and to estimate
      the heritabilities of these eye diseases in the wild-boar-colored wirehaired
      Dachshunds (WWD) bred in the German Dachshund Club 1888 e.V. (DTK). Data included
      2,430 WWD born between 1995 and 2003 that were examined between 1996 and 2005 by
      veterinary ophthalmologists. CAT was diagnosed in 3.83% of the 2,430 dogs, FCN in
      3.74%, and PSL in 2.76%. Sex, size, inbreeding coefficient, the age of the dog at
      examination, experience of the veterinary ophthalmologist and the additive
      genetic effect of the animal were considered in the multivariate linear model.
      The age of the dog at examination had a significant influence on the prevalence
      of FCN. The degree of experience of the veterinary ophthalmologist significantly
      influenced the prevalence of FCN and PSL. Using a transformation into the
      Dempster-Lerner threshold model, heritability estimates (h(DL)2) for WWD were
      h(DL)2 = 0.39 +/- 0.13 for CAT, h(DL)2 = 0.36 +/- 0.11 for FCN and h(DL)2 = 0.49
      +/- 0.12 for PSL. Positive genetic correlations (r(g)) were found between CAT and
      FCN (r(g) = 0.58 +/- 0.21), between PSL and FCN (r(g) = 0.83 +/- 0.23), and
      between CAT and PSL (r(g) = 0.79 +/- 0.06). The eye diseases investigated here in
      the Dachshund were found to be genetically influenced and positively correlated
      traits.

PMID- 18712266
TI  - [Review of literature and results from test matings of East Friesian milk sheep
      affected with brachygnathia inferior].
AB  - Shortness of the lower jaw (brachygnathia inferior, underbite, overshot, parrot
      mouth) is an inborn and mostly hereditary malformation often seen in many sheep
      breeds. Chromosomal anomalies are generally not involved in brachygnathia
      inferior. Viral infections, teratogenic drugs and alkaloids of plants often lead
      to craniofacial malformations associated with brachygnathia inferior. A maternal
      deficiency of iron is discussed as a cause for brachygnathia inferior. We
      performed a three-year breeding trial using mainly East Friesian milk sheep
      affected by brachygnathic occlusion. Mating schemes included affected by affected
      and affected by unaffected matings. In the breeding trial, 60 lambs were born and
      from these 37 animals had variable degrees of brachygnathia inferior. The
      brachygnathic condition increased with rising age of the lambs. Extremely
      affected lambs showed palatine ulcers and growth retardation. Moreover, some
      animals had abnormal positions of the incisor teeth, distortion of the lower jaw
      and deformities of the external ear. Analysis of the pedigree did not support a
      monogenic inheritance pattern. An oligogenic inheritance including a dominant and
      recessive locus responsible for the major gene effects and possibly further
      modifying loci appeared much more likely. Other causes for brachygnathia inferior
      such as viral infections and anemia of the ewes could be ruled out. Chromosomal
      abnormalities were not evident and thus, large chromosomal defects were not
      associated with brachygnathia inferior.

PMID- 18712267
TI  - Bluetongue control--a new challenge for Europe.

PMID- 18712268
TI  - Perioperative outcomes of the Prolift pelvic floor repair systems following
      introduction to a urogynecology teaching service.
AB  - The safety information of the vaginal mesh systems upon introduction to a
      teaching urogynecology service is limited to date. To determine the frequency of
      perioperative complications associated with the use of Prolift kits
      (Gynecare/Ethicon, Somerville, NJ, USA) by a teaching urogynecology service, data
      from the first 100 consecutive women were analyzed. The primary outcome was any
      deviation from a normal intraoperative or perioperative course. Complications
      were graded using the Dindo morbidity scale. Univariate analyses were performed
      to identify risk factors. Complications included bladder perforation (2%), blood
      transfusion (2%), mesh exposure (4%), and urinary tract infections (28%). Eleven
      percent of women reported postoperative pain, and 34% required catheterization at
      discharge for incomplete bladder emptying. Univariate analysis showed no
      association between morbidities and patient characteristics, attending
      experience, or fellow involvement. The integration of Prolift kits for prolapse
      repair into a urogynecology training program can be achieved with few
      perioperative complications.

PMID- 18712269
TI  - Acute type II cryoglobulinaemic vasculitis mimicking atherosclerotic peripheral
      vascular disease.
AB  - Atherosclerotic peripheral vascular disease is a common presenting cause for
      digital ischaemia in life long smokers. Acute severe Type II Cryoglobulinaemic
      vasculitis is a rare yet important cause, which may present with similar clinical
      features and which if undiagnosed may be rapidly fatal. Following the instigation
      of therapy with intravenous methylprednisolone and cyclophosphamide this patient
      made an excellent recovery.

PMID- 18712270
TI  - Division of the right posterior attachments of the head of the pancreas with a
      linear stapler during pancreaticoduodenectomy: vascular and oncological
      considerations based on an anatomical cadaver-based study.
AB  - BACKGROUND: Section of the right posterior attachment (RPA) of the pancreatic
      head from the adventicia of the superior mesenteric artery (SMA) is the last step
      of pancreaticoduodenectomy. This procedure might be technically demanding, time
      consuming and potentially dangerous. A method using a stapler has been proposed
      to simplify this step of the pancreaticoduodenectomy. METHODS: To evaluate the
      potential consequences of RPA section using this new method, we used an
      experimental model of pancreaticoduodenectomy in 20 cadavers. After RPA stapling,
      the residual areolar tissue located between the staple line and SMA was removed
      (by sub adventicial dissection) and weighed. This allowed an evaluation of: (1)
      the theoretical risk of SMA injury and (2) the potential carcinological
      consequences of using stapling division, in comparison with the lymphadenectomy
      obtained with the conventional sub-adventicial dissection. RESULTS: A right
      hepatic artery was accidentaly injured in 10% of cases because of the lack of
      arterial dissection and arterial anatomy recognition. Forty-three percent of the
      RPA containing nerves and lymphatics remains in place. Using the stapling
      technique for RPA division theoretically increases the risk of micro or
      macroscopically positive margin after surgical resection. CONCLUSION: The result
      of this human cadaver-based dissection suggests that the use of the mechanical
      stapling device for final division of the RPA might increase the risk of SMA
      injury. The risk of vascular injury has been reported in surgical literature and
      is confirmed by this study. Such results (10% of accidentaly injury) may not be
      representative in leaving human patients, thanks to the use of a detectable
      palpable pulse of the SMA. The latter is important in avoiding vascular injury
      during RPA division. This study also shows that this new technique may increase
      the risk of incomplete tumor resection.

PMID- 18712271
TI  - Altered urinary polyamine patterns of cancer patients under acupuncture therapy.
AB  - The reduction of elevated polyamine (PA) levels in biological fluids of cancer
      patients were known to be correlated with remission following diverse therapeutic
      treatments. In this study, altered urinary PA levels from three different cancer
      cases were monitored at different intervals during the long-term weekday
      acupuncture treatments. Nine urinary PA levels from 16 normal and three cancer
      patients with different types were measured by gas chromatography-mass
      spectrometry in selected ion monitoring mode as N-ethoxycarbonyl-N
      pentafluoropropionyl derivatives. Their levels measured at three follow-up stages
      for each patient were then normalized to the corresponding normal group means and
      plotted into star symbol patterns. Large alterations of PA levels were observed
      for each patient. Each normalized concentration displayed elevation of the PA
      levels in multiples (0.0-57.7) of the respective normal mean values. The
      normalized PA values were transformed into distorted star patterns which were
      characteristic of each follow-up stage and of cancer type.

PMID- 18712272
TI  - A conceptual model of the polyamine binding site of N1-acetylpolyamine oxidase
      developed from a study of polyamine derivatives.
AB  - We used various polyamine derivatives to study the substrate binding site of N1
      acetylpolyamine oxidase (PAO) that was partially purified from rat liver. The
      substrate activities of acetylpolyamines indicated the presence of two anionic
      centers corresponding to the 1,3-diaminopropane (1,3-DAP) structure and a
      hydrophobic region in addition to the cleavage site of the acetamidopropyl group.
      Based on the results of the inhibitory activities of 1,3-DAP derivatives, we
      developed a conceptual model of the polyamine binding site of PAO. We used this
      model to identify a potent competitive inhibitor, N1,N7-dihexyl-1,7-diamino-4
      azaheptane, and to develop an affinity column, 1,16-diamino4,13-diazahexadecane
      linked Sepharose, which was useful for the purification of PAO.

PMID- 18712273
TI  - Dietary L-arginine supplementation enhances the immune status in early-weaned
      piglets.
AB  - This study was conducted to test the hypothesis that dietary L-arginine
      supplementation enhances immunity in early weaned piglets. Seventy piglets weaned
      at 7 days of age were assigned to five groups (14 pigs/group), representing
      supplementation of 0.0, 0.2, 0.4, 0.6, and 0.8% L-arginine to a milk-based
      formula. On Day 7 after initiation of treatment, spleen weight in piglets
      supplemented with 0.2 and 0.8% arginine was heavier and thymus size was larger in
      piglets supplemented with 0.6% arginine, whereas serum concentration of
      immunoglobulin (Ig) M was higher but that of IL-8 was lower in piglets
      supplemented with 0.6 and 0.8% arginine, compared with the control group. Dietary
      supplementation with 0.8% arginine increased the numbers of white blood cells and
      granulocytes, and gene expression of interleukin (IL)-8 in spleen. On Day 14,
      compared with control piglets, granulocyte numbers were greater but lymphocyte
      numbers were lower in piglets supplemented with 0.2 and 0.4% arginine, whereas
      splenic expression of IL-8 and tumor necrosis factor-alpha genes was increased in
      piglets supplemented with 0.8% arginine. Additionally, IgG and IgM concentrations
      in serum and growth performance were greater in piglets supplemented with 0.4
      0.8% arginine, compared with unsupplemented piglets. Collectively, dietary
      supplementation with 0.4-0.8% L-arginine for 2 weeks enhances both cellular and
      humoral immunity in piglets by modulating the production of leukocytes, cytokines
      and antibodies. These results indicate that increasing L-arginine provision is
      beneficial for optimal immune responses in young pigs and also have important
      implications for designing the next generation of improved formula for human
      infants.

PMID- 18712274
TI  - Genetic interactions model among Eotaxin gene polymorphisms in asthma.
AB  - Eotaxin family (Eotaxin 1,2 and 3) recruits and activates CCR3-bearing cells such
      as eosinophil, mast cells, and Th2 lymphocytes that play a major role in allergic
      disorders. We examined the polygenetic effects of the Eotaxin gene family in a
      Korean population. Gene-gene interactions were tested using a multistep approach
      with multifactor dimensionality reduction (MDR) method between asthmatics and
      normal controls. The overall best MDR model of the main effect single nucleotide
      polymorphisms (SNPs) included EOT2 + 1272A > G and EOT3 + 77C > T (model 1)
      [testing accuracy 0.597, cross-validation consistency (CVC) 10/10, P < 0.001].
      The overall best MDR model of the SNPs with no main effects included EOT2 + 304C
      > A, EOT3 + 716A > G, and EOT3 + 1579G > A (model 2) (testing accuracy 0.616, CVC
      10/10, P < 0.001). Model 3 was obtained by including the MDR variables for models
      1 and 2. This new composite model predicted asthma with better accuracy than
      either model 1 or model 2 (testing accuracy 0.643, CVC 10/10, P < 0.001). The
      detection of statistical interaction models is one evidence of gene-gene
      interactions among Eotaxin genes, and this interaction is thought to influence
      the development of asthma. Although the models are limited to determining
      statistical interactions within a population, they may be useful for identifying
      groups at high risk of developing asthma.

PMID- 18712275
TI  - Development of a self-reporting questionnaire, BURMIG, to evaluate the burden of
      migraine.
AB  - We developed a 77-item self-reporting questionnaire to assess the burden of
      migraine (BURMIG), including headache characteristics, migraine associated
      disability, comorbidities, management, and the consequences on the patients'
      lives. We translated BURMIG into four languages (French, Portuguese, German and
      English) and tested it in 130 headache patients (20 pain clinic, 17 primary care
      and 93 general public) in Luxembourg. We performed a linguistic and a face
      content validation and tested the questionnaire for its comprehensiveness,
      internal consistency and for its retest-reliability at an interval of 1 month
      (completion rates were 79.6 and 76.4%, for test and retest, respectively). Retest
      reliability for the different parts of the questionnaire varied between 0.6 and
      1.0 (Kappa coefficient), with an intracorrelation coefficient of 0.7-1.0. The
      internal consistency was between 0.74 and 0.91 (Cronbach's alpha). The
      questionnaire BURMIG is suitable to evaluate the burden of migraine and can be
      used in English, German, French and Portuguese.

PMID- 18712276
TI  - Structural biology of the purine biosynthetic pathway.
AB  - Purine biosynthesis requires ten enzymatic transformations to generate inosine
      monophosphate. PurF, PurD, PurL, PurM, PurC, and PurB are common to all pathways,
      while PurN or PurT, PurK/PurE-I or PurE-II, PurH or PurP, and PurJ or PurO
      catalyze the same steps in different organisms. X-ray crystal structures are
      available for all 15 purine biosynthetic enzymes, including 7 ATP-dependent
      enzymes, 2 amidotransferases and 2 tetrahydrofolate-dependent enzymes. Here we
      summarize the structures of the purine biosynthetic enzymes, discuss similarities
      and differences, and present arguments for pathway evolution. Four of the ATP
      dependent enzymes belong to the ATP-grasp superfamily and 2 to the PurM
      superfamily. The amidotransferases are unrelated, with one utilizing an N
      terminal nucleophileglutaminase and the other utilizing a triad glutaminase.
      Likewise the tetrahydrofolate-dependent enzymes are unrelated. Ancestral proteins
      may have included a broad specificity enzyme instead of PurD, PurT, PurK, PurC,
      and PurP, and a separate enzyme instead of PurM and PurL.

PMID- 18712277
TI  - Mechanisms of synaptic depression triggered by metabotropic glutamate receptors.
AB  - Glutamate, by activation of metabotropic receptors (mGluRs), can lead to a
      reduction of synaptic efficacy at many synapses. These forms of synaptic
      plasticity are referred to as long-term depression (mGluR-LTD). We will
      distinguish between mGluR-LTD induced by pre- or postsynaptic receptors and mGluR
      LTD induced by the locus of the expression mechanism of the synaptic depression.
      We will also review recent evidence that mGluR-mediated responses themselves are
      subject to depression, which may constitute a form of metaplasticity.

PMID- 18712278
TI  - Myeloid sarcoma presenting as a recurrent, multifocal nerve root entrapment
      syndrome.
AB  - BACKGROUND: Myeloid sarcoma is an extramedullary manifestation of haematologic
      malignancy, most commonly acute myeloid leukemia (AML), which can cause
      neurological symptoms. CASE DESCRIPTION: A 45-year-old male with a history of AML
      presented with a lumbosacral nerve root entrapment syndrome followed by cauda
      equina compression, but without systemic signs of AML recurrence. MRI showed a
      mass compressing the spinal cord at level L5-S2. After surgically removing the
      tumour pathologic examination yielded a myeloid sarcoma. Combined chemotherapy
      and radiation therapy followed. Five months later the patient developed a
      thoracal (Th10-Th11) radiculopathy due to a relapse of the myeloid sarcoma,
      followed by C8-Th1-radiculopathy caused by leptomeningeal spread. CONCLUSION:
      This case forms the first description of recurrent, multifocal and progressive
      radiculopathy due to myeloid sarcoma. This diagnosis should be considered in
      patients with radiculopathy with previous haematological malignancy and/or signs
      or symptoms of such disease; the absence of systemic disease activity does not
      rule out myeloid sarcoma.

PMID- 18712279
TI  - Long-lasting successful cerebral response with sorafenib in advanced renal cell
      carcinoma.
AB  - We report the case of a 75-year old woman who received sorafenib (Nexavar), Bayer
      Pharmaceuticals Corporation, West Haven, CT) for a CNS relapse of clear cell
      renal cell carcinoma. After four months of sorafenib treatment, a brain magnetic
      resonance imaging showed 95%-volumetric regression of cerebral metastasis. To the
      best of our knowledge, this is the first almost complete resolution of brain
      metastases in renal cell carcinoma treated with sorafenib that has been
      described.

PMID- 18712280
TI  - Neuroradiological assessment of newly diagnosed glioblastoma.

PMID- 18712281
TI  - Surgical management of newly diagnosed glioblastoma in adults: role of
      cytoreductive surgery.

PMID- 18712282
TI  - Diagnosis of malignant glioma: role of neuropathology.

PMID- 18712283
TI  - Radiation therapy of pathologically confirmed newly diagnosed glioblastoma in
      adults.

PMID- 18712285
TI  - The emergence of clinical practice parameter guidelines in neuro-oncology:
      promise of utility tempered with caution.

PMID- 18712284
TI  - Cytotoxic chemotherapeutic management of newly diagnosed glioblastoma multiforme.

PMID- 18712286
TI  - Hormone induced changes in lactase glycosylation in developing rat intestine.
AB  - Lactase exists in both soluble and membrane-bound forms in suckling rat
      intestine. The distribution of lactase and its glycosylated isoforms in response
      to thyroxine or cortisone administration has been studied in suckling rats. 75%
      of lactase activity was detected, associated with brush borders, compared to 24%
      in the soluble fraction of 8-day-old rats. Thyroxine treatment enhanced soluble
      lactase activity to 34%, whereas particulate fraction was reduced to 67% compared
      to controls. Cortisone administration reduced soluble lactase activity from 24%
      in controls to 12% with a concomitant increase in membrane-bound activity to 89%.
      Western blot analysis revealed lactase signal, corresponding to 220 kDa in both
      the soluble and membrane fractions, which corroborated the enzyme activity data.
      The elution pattern of papain solubilized lactase from agarose-Wheat Germ
      agglutinin, or Concanavalin A or Jacalin agglutinin columns was different in the
      suckling and adult rat intestines. Also the elution profile of lactase activity
      from agarose-lectin columns was modulated in cortisone, thyroxine, and insulin
      injected pups, which suggests differences in glycosylated isoforms of lactase
      under these conditions. These findings suggest the role of these hormones in
      inducing changes in lactase glycosylation during postnatal development of
      intestine, which may contribute to adult-type hypolactasia in rats.

PMID- 18712287
TI  - Unilateral optic nerve aplasia associated with rudimental retinal vasculature.
AB  - Optic nerve aplasia (ONA) is a rare congenital malformation characterized by
      absence of optic disk, optic nerve, retinal ganglion cells, and central retina
      vessels. It is frequently associated with other ocular and central nervous system
      anomalies. In this paper, we describe a case of ONA associated with
      microphthalmos and a rudimental retinal vasculature in an otherwise healthy
      infant.

PMID- 18712288
TI  - Rapid determination of L-glutamine using engineered Escherichia coli
      overexpressing glutamine synthetase.
AB  - A genetically engineered Escherichia coli was developed as the source of enzyme
      for rapidly quantifying glutamine. E. coli BL21 (DE3) cells overexpressing a
      glutamine synthetase from Bacillus subtilis were prepared as tube aliquots and
      used in a small volume of nontoxic mixture. The current method was compared to
      high performance liquid chromatography analysis, Sigma kit (GLN-1) and Mecke
      method. The method is applicable to a wide range of glutamine concentrations
      (0.05-2.5 mM) and correlates well to the detection results obtained from high
      performance liquid chromatography (Pearson correlation is 0.978 at the 0.01
      level). Moreover, the whole assay procedure takes less than 15 min and uses
      nontoxic reagents, so it can be applied to monitor glutamine production and
      utilization conveniently.

PMID- 18712289
TI  - Variable volume fed-batch fermentation for nisin production by Lactococcus lactis
      subsp. lactis W28.
AB  - A feeding technology that was suitable for improving the nisin production by
      Lactococcus lactis subsp. lactis W28 was established. The effects of initial
      sucrose concentration (ISC) in the fermentation broth, feeding time, and feeding
      rate on the fermentation were studied. It was observed that a fed-batch culture
      (ISC = 10 g l(-1)) with 100 ml sucrose solution (190 g l(-1)) being evenly fed (9
      10 ml h(-1)) into the fermenter after 3-h fermentation gave the best performance
      in terms of biomass and nisin yield. Under these conditions, the total biomass
      and the total nisin yield were approximately 23% and 51% higher than those in
      batch fermentation, respectively. When the sucrose concentration was controlled
      at 5-10 g l(-1) in variable volume intermittent fed-batch fermentation (VVIF)
      with ISC = 10 g l(-1), the total biomass and the total nisin yield were 29% and
      60% above those in batch fermentation, respectively. The VVIF proved to be
      effective to eliminate the substrate inhibition by maintaining sucrose at
      appropriate levels. It is also easy to be scaled up, since various parameters
      involved in industrial production were taken into account.

PMID- 18712290
TI  - Purification, characterization, and preliminary X-ray diffraction analysis of a
      lactose-specific lectin from Cymbosema roseum seeds.
AB  - The unique carbohydrate-binding property of lectins makes them invaluable tools
      in biomedical research. Here, we report the purification, partial primary
      structure, carbohydrate affinity characterization, crystallization, and
      preliminary X-ray diffraction analysis of a lactose-specific lectin from
      Cymbosema roseum seeds (CRLII). Isolation and purification of CRLII was performed
      by a single step using a Sepharose-4B-lactose affinity chromatography column. The
      carbohydrate affinity characterization was carried using assays for
      hemagglutination activity and inhibition. CRLII showed hemagglutinating activity
      toward rabbit erythrocytes. O-glycoproteins from mucine mucopolysaccharides
      showed the most potent inhibition capacity at a minimum concentration of 1.2
      microg mL(-1). Protein sequencing by mass spectrometry was obtained by the
      digestion of CRLII with trypsin, Glu-C, and AspN. CRLII partial protein sequence
      exhibits 46% similarity with the ConA-like alpha chain precursor. Suitable
      protein crystals were obtained with the hanging-drop vapor-diffusion method with
      8% ethylene glycol, 0.1 M Tris-HCl pH 8.5, and 11% PEG 8,000. The monoclinic
      crystals belong to space group P2(1) with unit cell parameters a = 49.4, b =
      89.6, and c = 100.8 A.

PMID- 18712291
TI  - Production of anti-methicillin-resistant Staphylococcus activity from Bacillus
      subtilis sp. strain B38 newly isolated from soil.
AB  - B38 bacterial strain, isolated from Tunisian soil showed a strong antimicrobial
      activity. Based on biochemical characterization and 16S rDNA sequence analysis,
      B38 strain was identified as Bacillus subtilis. Cell culture supernatant showed
      antibacterial activity against clinical isolates of methicillin-resistant
      Staphylococcus species and several Gram-positive and Gram-negative bacteria.
      Antifungal activity against phytopathogenic fungi was also observed.
      Antibacterial activity production started at early exponential growth phase, and
      maximum activity was reached at the stationary phase. This antibacterial activity
      was neither affected by proteases, lipase, and organic solvents, nor by
      surfactants. It was stable over a wide pH range and still active after
      autoclaving at 121 degrees C during 20 min. Thin layer chromatography followed by
      bioautography assay allowed the detection of four active spots with R(f) values
      of 0.30, 0.47, 0.70, and 0.82. The single spot with R (f) 0.30 showed antifungal
      activity, whereas the spots with R(f) values of 0.47, 0.70, and 0.82 exhibited
      antibacterial activity.

PMID- 18712292
TI  - DJ-1 changes in G93A-SOD1 transgenic mice: implications for oxidative stress in
      ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, lethal, neurodegenerative
      disorder. The causes of ALS are still obscure. Accumulating evidence supports the
      hypothesis that oxidative stress and mitochondrial dysfunction can be implicated
      in ALS pathogenesis. DJ-1 plays an important role in the oxidative stress
      response. The aim of this study was to discover whether there are changes in DJ-1
      expression or in DJ-1-oxidized isoforms in an animal model of ALS. We used mutant
      SOD1(G93A) transgenic mice, a commonly used animal model for ALS. Upregulation of
      DJ-1 mRNA and protein levels were identified in the brains and spinal cords of
      SOD1(G93A) transgenic mice as compared to wild-type controls, evident from an
      early disease stage. Furthermore, an increase in DJ-1 acidic isoforms was
      detected, implying that there are more oxidized forms of DJ-1 in the CNS of
      SOD1(G93A) mice. This is the first report of possible involvement of DJ-1 in ALS.
      Since DJ-1 has a protective role against oxidative stress, it may suggest a
      possible therapeutic target in ALS.

PMID- 18712293
TI  - Intrathecal anti-alphaB-crystallin IgG antibody responses: potential inflammatory
      markers in Guillain-Barre syndrome.
AB  - OBJECTIVE: alphaB-crystallin (alphaBC), a small stress protein with
      cytoprotective and anti-apoptotic functions, is a potent antigen in autoimmune
      demyelinating diseases. To address the role of alphaBC in Guillain-Barre syndrome
      (GBS) we analyzed humoral responses against alphaBC in relation to clinical,
      electrophysiological and CSF features in GBS. METHODS: Anti-alphaBC-IgG
      antibodies were measured in serum and cerebrospinal fluid (CSF) of patients with
      GBS (n = 41), infectious inflammatory neurological diseases (n = 21), multiple
      sclerosis (n = 42), and other, non-inflammatory neurological disorders (n = 40)
      by ELISA using human recombinant alphaBC. Expression of alphaBC was
      immunohistochemically analyzed in postmortem peripheral nerve tissue of GBS and
      controls without neuropathy. RESULTS: Serum alphaBC-IgG antibody levels did not
      differ between disease groups, whereas alphaBC-IgG antibodies in CSF were
      increased in GBS and infectious inflammatory neurological diseases. Calculation
      of an antigen specific alphaBC-IgG index (alphaBC-Ig-G(CSF) x total
      IgG(CSF))/(alphaBC-IgG(Serum) x total IgG(Serum)) revealed significantly elevated
      values in patients with GBS compared to other disease groups (p < 0.001). alphaBC
      IgG indices exceeding a cut off value > 0.8 had an 85 % specificity and a 76 %
      sensitivity for GBS. alphaBC was overexpressed in dorsal root ganglia and spinal
      roots of autopsy cases with GBS. CONCLUSIONS: We demonstrate increased alphaBC
      IgG indices in a high proportion of our GBS patients, which reflect enhanced
      antigen-specific intrathecal antibody responses against abnormally expressed
      alphaBC in inflamed peripheral nerve tissue. Elevated alphaBC-IgG indices might
      therefore serve as markers of PNS inflammation and supplement currently used
      laboratory tests in the diagnosis of GBS.

PMID- 18712296
TI  - UNAFold: software for nucleic acid folding and hybridization.
AB  - The UNAFold software package is an integrated collection of programs that
      simulate folding, hybridization, and melting pathways for one or two single
      stranded nucleic acid sequences. The name is derived from "Unified Nucleic Acid
      Folding." Folding (secondary structure) prediction for single-stranded RNA or DNA
      combines free energy minimization, partition function calculations and stochastic
      sampling. For melting simulations, the package computes entire melting profiles,
      not just melting temperatures. UV absorbance at 260 nm, heat capacity change
      (C(p)), and mole fractions of different molecular species are computed as a
      function of temperature. The package installs and runs on all Unix and Linux
      platforms that we have looked at, including Mac OS X. Images of secondary
      structures, hybridizations, and dot plots may be computed using common formats.
      Similarly, a variety of melting profile plots is created when appropriate. These
      latter plots include experimental results if they are provided. The package is
      "command line" driven. Underlying compiled programs may be used individually, or
      in special combinations through the use of a variety of Perl scripts. Users are
      encouraged to create their own scripts to supplement what comes with the package.
      This evolving software is available for download at
      http://www.bioinfo.rpi.edu/applications/hybrid/download.php .

PMID- 18712297
TI  - Protein structure prediction.
AB  - Protein structure prediction has matured over the past few years to the point
      that even fully automated methods can provide reasonably accurate three
      dimensional models of protein structures. However, until now it has not been
      possible to develop programs able to perform as well as human experts, who are
      still capable of systematically producing better models than automated servers.
      Although the precise details of protein structure prediction procedures are
      different for virtually every protein, this chapter describes a generic procedure
      to obtain a three-dimensional protein model starting from the amino acid
      sequence. This procedure takes advantage both of programs and servers that have
      been shown to perform best in blind tests and of the current knowledge about
      evolutionary relationships between proteins, gained from detailed analyses of
      protein sequence, structure, and functional data.

PMID- 18712298
TI  - An introduction to protein contact prediction.
AB  - A fundamental problem in molecular biology is the prediction of the three
      dimensional structure of a protein from its amino acid sequence. However,
      molecular modeling to find the structure is at present intractable and is likely
      to remain so for some time, hence intermediate steps such as predicting which
      residues pairs are in contact have been developed. Predicted contact pairs have
      been used for fold prediction, as an initial condition or constraint for
      molecular modeling, and as a filter to rank multiple models arising from homology
      modeling. As contact prediction has advanced it is becoming more common for 3D
      structure predictors to integrate contact prediction into structure building, as
      this often gives information that is orthogonal to that produced by other
      methods. This chapter shows how evolutionary information contained in protein
      sequences and multiple sequence alignments can be used to predict protein
      structure, and the state-of-the-art predictors and their methodologies are
      reviewed.

PMID- 18712299
TI  - Analysis of mass spectrometry data in proteomics.
AB  - The systematic study of proteins and protein networks, that is, proteomics, calls
      for qualitative and quantitative analysis of proteins and peptides. Mass
      spectrometry (MS) is a key analytical technology in current proteomics and modern
      mass spectrometers generate large amounts of high-quality data that in turn allow
      protein identification, annotation of secondary modifications, and determination
      of the absolute or relative abundance of individual proteins. Advances in mass
      spectrometry-driven proteomics rely on robust bioinformatics tools that enable
      large-scale data analysis. This chapter describes some of the basic concepts and
      current approaches to the analysis of MS and MS/MS data in proteomics.

PMID- 18712300
TI  - The classification of protein domains.
AB  - The significant expansion in protein sequence and structure data that we are now
      witnessing brings with it a pressing need to bring order to the protein world.
      Such order enables us to gain insights into the evolution of proteins, their
      function, and the extent to which the functional repertoire can vary across the
      three kingdoms of life. This has led to the creation of a wide range of protein
      family classifications that aim to group proteins based on their evolutionary
      relationships. This chapter discusses the approaches and methods that are
      frequently used in the classification of proteins, with a specific emphasis on
      the classification of protein domains. The construction of both domain sequence
      and domain structure databases is considered and the chapter shows how the use of
      domain family annotations to assign structural and functional information is
      enhancing our understanding of genomes.

PMID- 18712301
TI  - Inferring function from homology.
AB  - Modern molecular biology approaches often result in the accumulation of abundant
      biological sequence data. Ideally, the function of individual proteins predicted
      using such data would be determined experimentally. However, if a gene of
      interest has no predictable function or if the amount of data is too large to
      experimentally assess individual genes, bioinformatics techniques may provide
      additional information to allow the inference of function. This chapter proposes
      a pipeline of freely available Web-based tools to analyze protein-coding DNA
      sequences of unknown function. Accumulated information obtained during each step
      of the pipeline is used to build a testable hypothesis of function. The basis and
      use of sequence similarity methods of homologue detection are described, with
      emphasis on BLAST and PSI-BLAST. Annotation of gene function through protein
      domain detection using SMART and Pfam, and the potential for comparison to whole
      genome data are discussed.

PMID- 18712302
TI  - The Rosetta stone method.
AB  - Analysis of amino acid sequences from different organisms often reveals cases in
      which two or more proteins encoded for separately in a genome also appear as
      fusions, either in the same genome or that of some other organism. Such fusion
      proteins, termed Rosetta stone sequences, help link disparate proteins together,
      and suggest the likelihood of functional interactions between the linked
      entities, describing local and global relationships within the proteome. These
      relationships help us understand the role of proteins within the context of their
      associations, and facilitate assignment of putative functions to uncharacterized
      proteins based on their linkages with proteins of known function.

PMID- 18712303
TI  - Inferring functional relationships from conservation of gene order.
AB  - The idea behind the gene neighbor method is that conservation of gene order in
      evolutionarily distant prokaryotes indicates functional association. The
      procedure presented here starts with the organization of all the genomes into
      pairs of adjacent genes. Then, pairs of genes in a genome of interest are mapped
      to their corresponding orthologs in other, informative, genomes. The final step
      is to determine whether the orthologs of each original pair of genes are also
      adjacent in the informative genome.

PMID- 18712304
TI  - Phylogenetic profiling.
AB  - Phylogenetic profiles describe the presence or absence of a protein in a set of
      reference genomes. Similarity between profiles is an indicator of functional
      coupling between gene products: the greater the similarity, the greater the
      likelihood of proteins sharing membership in the same pathway or cellular system.
      By virtue of this property, uncharacterized proteins can be assigned putative
      functions, based on the similarity of their profiles with those of known
      proteins. Profile comparisons, when extended to the entire genome, have the power
      to reveal functional linkages on a genome-wide scale (the functional
      "interactome"), elucidating both known and novel pathways and cellular systems.

PMID- 18712305
TI  - Phylogenetic shadowing: sequence comparisons of multiple primate species.
AB  - Comparisons between the sequence of the human genome and that of species at a
      variety of evolutionary distances from human have emerged as one of the most
      powerful strategies for identifying the functional coding and non-coding elements
      in the genome. Although the analysis of traits shared between human and distant
      relatives such as mouse or chicken can be effectively carried out through
      comparisons among the genomes of those organisms, analysis of traits specific to
      primates requires comparisons with our closest non-human primate relatives. In
      addition, comparisons of highly similar sequences simplify many computational
      problems in comparative genomics. This chapter describes a strategy for sequence
      comparisons between multiple primate species.

PMID- 18712306
TI  - Prediction of regulatory elements.
AB  - Finding the regulatory mechanisms responsible for gene expression remains one of
      the most important challenges for biomedical research. A major focus in cellular
      biology is to find functional transcription factor binding sites (TFBS)
      responsible for the regulation of a downstream gene. As wet-lab methods are time
      consuming and expensive, it is not realistic to identify TFBS for all
      uncharacterized genes in the genome by purely experimental means. Computational
      methods aimed at predicting potential regulatory regions can increase the
      efficiency of wet-lab experiments significantly. Here, methods for building
      quantitative models describing the binding preferences of transcription factors
      based on literature-derived data are presented, as well as a general protocol for
      scanning promoters using cross-species comparison as a filter (phylogenetic
      footprinting).

PMID- 18712307
TI  - Expression and microarrays.
AB  - High throughput methodologies have increased by several orders of magnitude the
      amount of experimental microarray data available. Nevertheless, translating these
      data into useful biological knowledge remains a challenge. There is a risk of
      perceiving these methodologies as mere factories that produce never-ending
      quantities of data if a proper biological interpretation is not provided. Methods
      of interpreting these data are continuously evolving. Typically, a simple two
      step approach has been used, in which genes of interest are first selected based
      on thresholds for the experimental values, and then enrichment in biologically
      relevant terms in the annotations of these genes is analyzed in a second step.
      For various reasons, such methods are quite poor in terms of performance and new
      procedures inspired by systems biology that directly address sets of functionally
      related genes are currently under development.

PMID- 18712308
TI  - Identifying components of complexes.
AB  - Identifying and analyzing components of complexes is essential to understand the
      activities and organization of the cell. Moreover, it provides additional
      information on the possible function of proteins involved in these complexes. Two
      bioinformatics approaches are usually used for this purpose. The first is based
      on the identification, by clustering algorithms, of full or densely connected sub
      graphs in protein-protein interaction networks derived from experimental sources
      that might represent complexes. The second approach consists of the integration
      of genomic and proteomic data by using Bayesian networks or decision trees. This
      approach is based on the hypothesis that proteins involved in a complex usually
      share common properties.

PMID- 18712309
TI  - Integrating functional genomics data.
AB  - The revolution in high throughput biology experiments producing genome-scale data
      has heightened the challenge of integrating functional genomics data. Data
      integration is essential for making reliable inferences from functional genomics
      data, as the datasets are neither error-free nor comprehensive. However, there
      are two major hurdles in data integration: heterogeneity and correlation of the
      data to be integrated. These problems can be circumvented by quantitative testing
      of all data in the same unified scoring scheme, and by using integration methods
      appropriate for handling correlated data. This chapter describes such a
      functional genomics data integration method designed to estimate the "functional
      coupling" between genes, applied to the baker's yeast Saccharomyces cerevisiae.
      The integrated dataset outperforms individual functional genomics datasets in
      both accuracy and coverage, leading to more reliable and comprehensive
      predictions of gene function. The approach is easily applied to multicellular
      organisms, including human.

PMID- 18712310
TI  - Computational diagnostics with gene expression profiles.
AB  - Gene expression profiling using micro-arrays is a modern approach for molecular
      diagnostics. In clinical micro-array studies, researchers aim to predict disease
      type, survival, or treatment response using gene expression profiles. In this
      process, they encounter a series of obstacles and pitfalls. This chapter reviews
      fundamental issues from machine learning and recommends a procedure for the
      computational aspects of a clinical micro-array study.

PMID- 18712311
TI  - Analysis of quantitative trait loci.
AB  - Diseases with complex inheritance are characterized by multiple genetic and
      environmental factors that often interact to produce clinical symptoms. In
      addition, etiological heterogeneity (different risk factors causing similar
      phenotypes) obscure the inheritance pattern among affected relatives and hamper
      the feasibility of gene-mapping studies. For such diseases, the careful selection
      of quantitative phenotypes that may represent intermediary risk factors for
      disease development (intermediate phenotypes) is etiologically more homogeneous
      than the disease per se. Over the last 15 years quantitative trait locus mapping
      has become a popular method for understanding the genetic basis for intermediate
      phenotypes. This chapter provides an introduction to classical and recent
      strategies for mapping quantitative trait loci in humans.

PMID- 18712312
TI  - Molecular similarity concepts and search calculations.
AB  - The introduction of molecular similarity analysis in the early 1990s has
      catalyzed the development of many small-molecule-based similarity methods to mine
      large compound databases for novel active molecules. These efforts have
      profoundly influenced the field of computer-aided drug discovery and
      substantially widened the spectrum of available ligand-based virtual screening
      approaches. However, the principles underlying the computational assessment of
      molecular similarity are much more multifaceted and complex than it might appear
      at first glance. Accordingly, intrinsic features of molecular similarity analysis
      and its relationship to other methods are often not well understood. This chapter
      discusses critical aspects of molecular similarity, an understanding of which is
      essential for the evaluation of method development in this field. Then it
      describes studies designed to enhance the performance of molecular fingerprint
      searching, which is one of the most intuitive and widely used similarity-based
      methods.

PMID- 18712313
TI  - Optimization of the MAD algorithm for virtual screening.
AB  - The approach termed Determination and Mapping of Activity-Specific Descriptor
      Value Ranges (MAD) is a conceptually novel molecular similarity method for the
      identification of active compounds. MAD is based on mapping of compounds to
      different (multiple) activity class-selective descriptor value ranges. It was
      recently developed in our laboratory and successfully applied in initial virtual
      screening trials. We have been able to show that selected molecular property
      descriptors can display a strong tendency to respond to unique features of
      compounds having similar biological activity, thus providing a basis for the
      approach. Accordingly, a crucial step of the MAD algorithm is the identification
      of activity-sensitive descriptor settings. The second critical step of MAD is the
      subsequent mapping of database compounds to activity-sensitive descriptor value
      ranges in order to identify novel active molecules. This chapter describes the
      optimization of the MAD approach and evaluates the second-generation algorithm on
      a number of different compound activity classes with a particular focus on the
      recognition of remote molecular similarity relationships.

PMID- 18712314
TI  - Combinatorial optimization models for finding genetic signatures from gene
      expression datasets.
AB  - The aim of this chapter is to present combinatorial optimization models and
      techniques for the analysis of microarray datasets. The chapter illustrates the
      application of a novel objective function that guides the search for high-quality
      solutions for sequential ordering of expression profiles. The approach is
      unsupervised and a metaheuristic method (a memetic algorithm) is used to provide
      high-quality solutions. For the problem of selecting discriminative groups of
      genes, we used a supervised method that has provided good results in a variety of
      datasets. This chapter illustrates the application of these models in an
      Alzheimer's disease microarray dataset.

PMID- 18712315
TI  - Genetic signatures for a rodent model of Parkinson's disease using combinatorial
      optimization methods.
AB  - This chapter illustrates the use of the combinatorial optimization models
      presented in Chapter 19 for the Feature Set selection and Gene Ordering problems
      to find genetic signatures for diseases using micro-array data. We demonstrate
      the quality of this approach by using a microarray dataset from a mouse model of
      Parkinson's disease. The results are accompanied by a description of the
      currently known molecular functions and biological processes of the genes in the
      signatures.

PMID- 18712316
TI  - Developing fixed-parameter algorithms to solve combinatorially explosive
      biological problems.
AB  - Fixed-parameter algorithms can efficiently find optimal solutions to some
      computationally hard (NP-hard) problems. This chapter surveys five main practical
      techniques to develop such algorithms. Each technique is circumstantiated by case
      studies of applications to biological problems. It also presents other known
      bioinformatics-related applications and gives pointers to experimental results.

PMID- 18712317
TI  - Clustering.
AB  - Clustering techniques are used to arrange genes in some natural way, that is, to
      organize genes into groups or clusters with similar behavior across relevant
      tissue samples (or cell lines). These techniques can also be applied to tissues
      rather than genes. Methods such as hierarchical agglomerative clustering, k-means
      clustering, the self-organizing map, and model-based methods have been used. This
      chapter focuses on mixtures of normals to provide a model-based clustering of
      tissue samples (gene signatures) and gene profiles.

PMID- 18712318
TI  - Visualization.
AB  - Visualization is a powerful method to present and analyze a large amount of data.
      It is increasingly important in bioinformatics and is used for exploring
      different types of molecular biological data, such as structural information,
      high throughput data, and biochemical networks. This chapter gives a brief
      introduction to visualization methods for bioinformatics and presents two
      commonly used techniques in detail: heatmaps and force-directed network layout.

PMID- 18712319
TI  - Constructing computational pipelines.
AB  - Many bioinformatics tasks involve creating a computational pipeline from existing
      software components and algorithms. The traditional approach is to glue
      components together using scripts written in a programming language such as Perl.
      However, a new, more powerful approach is emerging that promises to revolutionise
      the way bioinformaticians create applications from existing components, an
      approach based on the concept of the scientific workflow. Scientific workflows
      are created in graphical environments known as workflow management systems. They
      have many benefits over traditional program scripts, including speed of
      development, portability, and their suitability for developing complex,
      distributed applications. This chapter explains how to design and implement
      bioinformatics workflows using free, Open Source software tools, such as the
      Taverna workflow management system. We also demonstrate how new and existing
      tools can be deployed as Web services so that they can be easily integrated into
      novel computational pipelines using the scientific workflow paradigm.

PMID- 18712320
TI  - Text mining.
AB  - One of the fastest-growing fields in bioinformatics is text mining: the
      application of natural language processing techniques to problems of knowledge
      management and discovery, using large collections of biological or biomedical
      text such as MEDLINE. The techniques used in text mining range from the very
      simple (e.g., the inference of relationships between genes from frequent
      proximity in documents) to the complex and computationally intensive (e.g., the
      analysis of sentence structures with parsers in order to extract facts about
      protein-protein interactions from statements in the text). This chapter presents
      a general introduction to some of the key principles and challenges of natural
      language processing, and introduces some of the tools available to end-users and
      developers. A case study describes the construction and testing of a simple tool
      designed to tackle a task that is crucial to almost any application of text
      mining in bioinformatics--identifying gene/protein names in text and mapping them
      onto records in an external database.

PMID- 18712321
TI  - [Laryngeal mask LMA Supreme. Application by medical personnel inexperienced in
      airway management].
AB  - BACKGROUND: The Laryngeal Mask Airway Supreme (LMA-S) is a new disposable airway
      device that combines features of the LMA ProSeal (PLMA, gastric access) and LMA
      Fastrach (curved shaft to ease insertion) and has been available since April
      2007. METHODS: In a prospective study, 10 final year medical students or first
      year anesthesia residents, all with limited experience in LMA anesthesia, were
      requested to manage the airway of anesthetized female patients with the LMA-S
      size 4, who seemed normal on routine airway examination. Data collection included
      the success rates and duration for insertion, oropharyngeal leak pressures (OLP),
      fiber optic position and airway morbidity. RESULTS: A total of 30 patients were
      enrolled in the study. Insertion of the LMA-S was possible in 27 (90%) patients
      at the first attempt and in 3 (10%) at the second attempt. Ventilation was
      established in 18.3 s (range 10-30 s, standard deviation +/-4.2 s). Insertion of
      a gastric tube was possible in all patients at the first attempt. Mean OLP at the
      level of 60 cmH2O cuff pressure was 29.1 cmH2O (range 21-35 cmH2O, standard
      deviation +/-4.8 cmH2O). Laryngeal fit evaluated by fiber optic control was rated
      as optimal in all patients both immediately after insertion of the LMA-S and
      after end of surgery. Three patients (10%) complained of mild sore throat. No
      patient reported dysphagia or dysphonia. CONCLUSION: Insertion of the LMA-S was
      successful and possible in all patients in < or = 30 s with an optimal laryngeal
      fit, high OLPs and low airway morbidity. The LMA-S seems to be a device suitable
      for use in routine anesthesia and which can be safely used by medical personnel
      with limited clinical experience.

PMID- 18712322
TI  - [Livid polycyclic plaques of the lower extremities].
AB  - In 10%-55% of patients, leukemia cutis (LC) manifest as a symptom of acute
      myelomonocytic leukemia and is associated with a poor overall prognosis.
      Disseminated bluish-violet or red-brownish papules and plaques, nodules and also
      hemorrhagic ulcers may dominate the initial clinical picture. Importantly,
      nonspecific infiltrates (leukemids) must be differentiated from specific
      infiltrates of malignant cells in patients presenting with dermatoses and
      concomitant underlying hematopoietic neoplasms. The role of the dermatologist is
      the rapid clinical and dermatohistopathological diagnosis in order to allow
      immediate, adequate treatment of the patient's underlying systemic disease.

PMID- 18712323
TI  - [Possibilities and limits for treating psoriasis with biologics. Case reports].
AB  - The availability of biologics for the therapy of psoriasis has radically changed
      the options for systemic therapy of this disease. Their use is often coupled with
      a variety of restrictions--as a rule they are to be used as a 'last-line'
      therapy. The status of previous systemic therapy as a basic requirement for the
      use of biologics is analyzed and simultaneously, the possibilities of the
      physician to use the indication spectrum of biologics for the benefit of the
      patient are demonstrated by case reports.

PMID- 18712324
TI  - [Ultraviolet therapy in patients with chronic hand eczema].
AB  - Treatment of hand eczema is dominated by the administration of topical
      glucocorticosteriods. If topical treatment fails, the best second-line option is
      ultraviolet (UV) therapy alone or as combination therapy. UVB and PUVA (psoralen
      plus UVA) therapy is effective and has relatively few side effects. Due to the
      localized nature of the disease, topical PUVA therapy is preferable to systemic
      PUVA treatment. Among the topical methods, cream PUVA therapy is simple, safe and
      highly effective. Recent clinical studies have demonstrated the therapeutic
      efficacy of a new retinoid called alitretinoin, a 9-cis-retinoic acid. However,
      even this form of treatment does not lead to a complete cure in all patients.
      Under the primacy of multimodal treatment, UV therapy should be administered as
      combination therapy if oral retinoids are not sufficiently effective.

PMID- 18712325
TI  - [Gastric signet ring cell carcinoma presenting. An erysipelas-like cutaneous
      metastasis of the abdominal skin].
AB  - A 71-year-old patient presented with diffuse and poorly circumscribed
      erythematous plaques of the abdominal skin, present for 5 months. Histology
      revealed a diffuse infiltration of the entire dermis with cytokeratin-positive
      signet-ring-cells. Subsequently, an extensive search for a primary adenocarcinoma
      uncovered a locally advanced signet-ring-cell gastric carcinoma. There were no
      metastases to other organs. This case shows the unusual clinical-diagnostic
      sequence of a patient with a signet-ring-cell-carcinoma of the stomach presenting
      with an erysipelas-like cutaneous metastasis of the abdominal skin.

PMID- 18712326
TI  - [Immunization strategies for treating melanoma].
AB  - Malignant melanoma is a highly aggressive although immunogenic tumor which can be
      recognized and destroyed by the immune system. Therefore, immunotherapy has been
      represented an essential part of the therapeutic arsenal for decades. Besides non
      specific immunotherapeutic approaches (whole tumor cell vaccine, cytokine
      therapy, toll-like receptor agonists), targeted immunotherapy has been made
      possible by the identification of tumor-associated antigens. Despite undisputable
      successes, the ultimate breakthrough has not yet been achieved. This overview
      deals with the fundamental aspects of antigen-specific immunotherapy and
      highlights future strategies to improve its clinical efficacy.

PMID- 18712327
TI  - [A rare cause of facial asymmetry: nasoalveolar cyst: a clinical report].
AB  - Nasoalveolar cysts are rare nonodontogenic cysts that develop from the soft
      tissue in the mucobuccal area of the nasal ala. Their origin is a residuum of the
      nasolacrimal canal. CLINICAL CASE: A 45-year-old woman had been aware of a
      painless tumor at the base of the nose and in the region of the left nasal ala
      for several months. We diagnosed a nasolabial cyst, which was extirpated in toto
      through a combined transvestibular-transnasal approach.

PMID- 18712328
TI  - [Modified procedure for patient registration for navigation control instruments
      in ENT surgery].
AB  - PROBLEM: Surgical navigation and navigation-controlled instruments demand a
      robust and precise patient registration process. For navigation in the skull, a
      bite-splint-based registration method has been widely applied, which had to be
      manufactured by dental technicians. The additional cost and time could be avoided
      by directly using the manufactured imprint, which is prepared by the ENT surgeon
      in one step. MATERIAL AND METHODS: This study examined the re-positioning
      accuracy for three silicon materials in a laboratory study with a 3D measuring
      device (Faro-arm) after several re-positioning cycles (simulating erosion) in
      comparison to the gold standard. RESULTS: The mean deviation after two cycles was
      lower for all three materials compared to the gold standard. Only C-Silikon
      Optosil was better then the gold standard after all cycles and with a deviation
      of 0.17 mm it well below that of the conventional bite-splint (0.28 mm). The
      additional cost benefits of 10 euro per imprint compared to the bite-splint with
      >100 euro favor this material for clinical application. CONCLUSIONS: As a
      consequence of this investigation Optosil was successfully used in 6 patients
      during the period from 01.09.2007 to 30.11.2007. The bite-splint was manufactured
      completely in the ENT department and could be used during the planning CT and
      surgery. The resulting accuracy corresponded to the experiences gained in
      previous surgery with a maximum deviation of 0.87 mm. The favorable ergonomic
      characteristics for patient and surgeon could be confirmed. As a result of this
      study this clinic now exclusively uses the procedure described in this article
      for bite-splint-based registration.

PMID- 18712329
TI  - [Is section sign 116b of the Social Statutes Book V unconstitutional? Outpatient
      treatment in hospital between theory and practice].

PMID- 18712331
TI  - [Isolated fractures of the olecranon].
AB  - Fractures of the olecranon account for 7% of fractures in adult patients. Of all
      elbow fractures, 38% are isolated fractures of the olecranon. Falling on the 90
      degrees flexed elbow is the most common cause of isolated olecranon fractures.
      Reconstitution of the joint surface is the main treatment goal, as well as
      stability of the joint and full range of motion and muscular strength. This can
      only be achieved in most cases by open reduction and precision osteosynthesis.
      Tension band wiring and plate osteosynthesis are the most commonly used
      techniques. Operative therapy is the therapy of choice, since it permits early
      physical therapy. Some non-dislocated fractures and fractures in elderly and
      multimorbid patients are indications for conservative therapy.

PMID- 18712330
TI  - Emerging hurdles in stem cell therapy for peripheral vascular disease.
AB  - Peripheral vascular disease (PVD) is a growing medical problem in Western
      societies and presents itself mainly in two different clinical forms.
      Intermittent claudication is an early moderate manifestation, while patients with
      critical limb ischemia suffer from severe muscle tissue loss or ulcers and are at
      high risk for limb amputation. Unfortunately, many patients cannot be helped with
      currently available surgical or endovascular revascularization procedures because
      of the complex anatomy of the vascular occlusion and/or the presence of other
      risk factors. Noninvasive stem cell therapy has been proposed as an alternative
      for such patients. Although pioneering clinical experience with stem cell-related
      therapy seems promising, it is too early for general clinical use of this
      technique, since many questions remain unanswered. Indeed, while questions about
      safety, dose, and administration route/timing/frequency are the first ones to be
      addressed when designing a stem cell-based clinical approach, there is
      accumulating evidence from recent (pre-)clinical studies that other issues may
      also be at stake. For instance, the choice of stem cells to be used and its
      precise mechanism of action, the need/possibility for concurrent tissue
      regeneration in case of irreversible tissue loss, the differentiation degree and
      specific vascular identity of the transplanted cells, and the long-term survival
      of engrafted cells in the absence of a normal supportive tissue environment
      should be well considered. Here, rather than presenting a comprehensive and
      extensive overview on the current literature on stem/progenitor cells and
      revascularization, we highlight some of the outstanding issues emerging from the
      recent (pre-)clinical literature that may codetermine the successful application
      of stem cells in a wide range of PVD patients in the future.

PMID- 18712332
TI  - [Bilateral hydrothorax and hydromediastinum after puncture of the right
      subclavian vein].
AB  - Complications after the percutaneous insertion of central venous catheters are
      pneumothoraces, catheter-associated infections and thrombosis. In rare cases,
      late problems occur as a disruption of the main thoracic duct or vascular
      erosion. The developing pleural effusion must be analysed for other causes such
      as congestive heart disease, inflammatory or tumorous disease, pancreatitis, low
      blood protein, or subdiaphragmatic abscess. The following case report describes a
      rare catheter complication in a 16-year-old polytraumatised patient. The
      differentiation to a chylothorax and suitable therapy are described.

PMID- 18712333
TI  - [Operative treatment of isolated fractures of the olecranon].

PMID- 18712334
TI  - [Traumatic chronic instability of the proximal tibiofibular joint].
AB  - The rare condition of chronic instability of the proximal tibiofibular joint can
      be of traumatic or idiopathic origin and can lead to secondary arthritis. After
      conservative treatment for 6 months and persistent pain, operative treatment
      should be considered. We present a case of traumatic instability, ligament
      reconstruction with a part of the biceps femoris tendon, and postoperative return
      to full and painless sport activities.

PMID- 18712335
TI  - Chemically mediated burrow recognition in the Mexican tarantula Brachypelma
      vagans female.
AB  - Chemically mediated communication is common in spiders but has been poorly
      studied in burrowing tarantulas. This study aimed to determine whether chemical
      cues influence the behaviour of females of Brachypelma vagans, a Mexican species
      of tarantula, during encounters with previously inhabited burrows or with
      extracts from the silk of conspecific females. In laboratory choice tests, female
      tarantulas entered a burrow that had previously been inhabited by a conspecific
      female significantly more frequently than a burrow that had never been inhabited.
      The identity of the previous inhabitant also affected the number of spiders that
      chose to enter a burrow. Spiders were quicker to choose and enter a burrow
      previously inhabited by themselves than a burrow previously inhabited by a
      conspecific or a burrow that had not been previously inhabited. Hexane, methanol
      and dichloromethane extracts of conspecific silk elicited different responses
      from female tarantulas when extracts were placed on filter paper disks at one end
      of an experimental arena with a control filter paper disk, on to which the
      corresponding solvent alone had been pipetted, placed on the other end of the
      arena. Spiders showed the strongest responses to hexane extracts of silk, with a
      significant preference to move towards the hexane extract and a significantly
      greater period of time spent in proximity to the hexane extract compared to the
      control disk. Overall and in contrast to expectations, tarantulas were most
      strongly attracted to the cues left by other conspecific females. As encounters
      between B. vagans females usually lead to aggression and mortality of one of the
      participants, we conclude that chemical cues are not signals that are
      deliberately released by burrow-inhabiting females but may inadvertently escape
      and cannot be easily suppressed.

PMID- 18712336
TI  - Divergent evolution of feeding substrate preferences in a phylogenetically young
      species flock of pupfish (Cyprinodon spp.).
AB  - A fundamental question in sympatric speciation is how trophic divergence is
      achieved. We used an extremely young (<8,000 years) species flock of pupfish
      (Cyprinodon spp.) from Laguna Chichancanab in south-eastern Mexico to examine
      divergent evolution of preferences for different feeding substrates. In a test
      aquarium, we presented four feeding substrates (sand, gravel, a plastic plant,
      and blank bottom), but no actual food was offered. The four feeding substrates
      were chosen to mirror the most common substrate types in Laguna Chichancanab.
      Previous studies demonstrated that benthic food items prevail in the diet of most
      Cyprinodon species. C. beltrani preferred sand, whereas C. labiosus preferred
      gravel. F(1) hybrids of both species showed intermediate preferences. C. maya
      searched for food equally at all substrates. As the test fish were reared under
      identical laboratory conditions (i.e., in the absence of feeding substrates), the
      species-specific preferences appear to be genetically fixed, suggesting rapid
      divergent evolution of feeding behaviors.

PMID- 18712337
TI  - Emergence of long distance bird migrations: a new model integrating global
      climate changes.
AB  - During modern birds history, climatic and environmental conditions have evolved
      on wide scales. In a continuously changing world, landbirds annual migrations
      emerged and developed. However, models accounting for the origins of these avian
      migrations were formulated with static ecogeographic perspectives. Here I
      reviewed Cenozoic paleoclimatic and paleontological data relative to the
      palearctic-paleotropical long distance (LD) migration system. This led to propose
      a new model for the origin of LD migrations, the 'shifting home' model (SHM). It
      is based on a dynamic perspective of climate evolution and may apply to the
      origins of most modern migrations. Non-migrant tropical African bird taxa were
      present at European latitudes during most of the Cenozoic. Their distribution
      limits shifted progressively toward modern tropical latitudes during periods of
      global cooling and increasing seasonality. In parallel, decreasing winter
      temperatures in the western Palearctic drove shifts of population winter ranges
      toward the equator. I propose that this induced the emergence of most short
      distance migrations, and in turn LD migrations. This model reconciliates
      ecologically tropical ancestry of most LD migrants with predominant winter range
      shifts, in accordance with requirements for heritable homing. In addition, it is
      more parsimonious than other non-exclusive models. Greater intrinsic plasticity
      of winter ranges implied by the SHM is supported by recently observed impacts of
      the present global warming on migrating birds. This may induce particular threats
      to some LD migrants. The ancestral, breeding homes of LD migrants were not
      'northern' or 'southern' but shifted across high and middle latitudes while
      migrations emerged through winter range shifts themselves.

PMID- 18712338
TI  - [New imaging strategies for monitoring molecular pharmacotherapy of GIST].
AB  - Prognosis and clinical management of patients with gastrointestinal stromal
      tumors (GIST) has changed significantly with the introduction of new molecular
      targeted drugs such as imatinib. This development is accompanied by a need to re
      evaluate the established imaging criteria used to assess treatment response. The
      frequently used response evaluation criteria in solid tumors (RECIST) are mainly
      based on one-dimensional tumor size and do not take into account functional
      changes in responding GISTs such as a decrease in CT density or in the number of
      intratumoral vessels. Positron emission tomography (PET) has been found to be
      highly sensitive in detecting early response and to have a predictive value in
      the long term response to imatinib treatment. Monitoring the course of the
      disease by PET is limited due to scanner availability and economic constraints.
      Modified CT response criteria using a combination of tumor density and tumor size
      are especially promising in early response assessment and have a good prognostic
      value. Further optimization of existing response criteria and evaluation of new
      candidate markers of treatment response, such as quantitative perfusion will be
      the key for optimized monitoring of targeted therapies in GIST.

PMID- 18712339
TI  - [Infrarenal abdominal aortic aneurysm: endovascular repair with stent grafts].
AB  - As an alternative to surgery, endovascular therapy with stent grafts has become
      the second main treatment option for infrarenal abdominal aortic aneurysms.
      Unlike surgery, endovascular treatment with stent grafts is also applicable in
      patients unfit for open repair. Despite current improvements in endovascular
      repair devices, significant anatomic barriers still exclude this technique for a
      large number of patients. Computed tomography, magnetic resonance imaging, and
      ultrasound are essential for diagnostics, preintervention planning, and
      postintervention follow-up of abdominal aneurysms treated with stent grafts. This
      review covers etiology, pathology, and diagnostic aspects. Materials and methods
      for endovascular treatment of abdominal aortic aneurysms are presented in detail,
      and clinical results and complications are discussed.

PMID- 18712340
TI  - Development of SRAP, SRAP-RGA, RAPD and SCAR markers linked with a Fusarium wilt
      resistance gene in eggplant.
AB  - Fusarium wilt (Fusarium oxysporum Schlecht. f. sp. melongenae) is a vascular
      disease of eggplant (Solanum melongena L.). The objectives of this work were (1)
      to confirm the monogenic inheritance of fusarium wilt resistance in eggplant, (2)
      to identify molecular markers linked to this resistance, and (3) to develop SCAR
      markers from most informative markers. We report the tagging of the gene for
      resistance to fusarium wilt (FOM) in eggplant using SRAP, RGA, SRAP-RGA and RAPD
      markers. Analysis of segregation data confirmed the monogenic inheritance of
      resistance. DNA from F(2) and BC(1) populations of eggplant segregating for
      fusarium wilt resistance was screened with 2,316 primer combinations to detect
      polymorphism. Three markers were linked within 2.6 cM of the gene. The codominant
      SRAP marker Me8/Em5 and dominant SRAP-RGA marker Em12/GLPL2 were tightly linked
      to each other and mapped 1.2 cM from the resistance gene, whereas RAPD marker H12
      mapped 2.6 cM from the gene and on the same side as the other two markers. The
      SRAP marker was converted into two dominant SCAR markers that were confirmed to
      be linked to the resistance gene in the F(2,) BC(1) and F(2) of BC(3) generations
      of the same cross. These markers provide a starting point for mapping the
      eggplant FOM resistance gene in eggplant and for exploring the synteny between
      solanaceous crops for fusarium wilt resistance genes. The SCAR markers will be
      useful for identifying fusarium wilt-resistant genotypes in marker-assisted
      selection breeding programs using segregating progenies of the resistant eggplant
      progenitor used in this study.

PMID- 18712341
TI  - A region of barley chromosome 6H harbors multiple major genes associated with net
      type net blotch resistance.
AB  - Net type net blotch (NTNB), caused by Pyrenophora teres f. teres Drechs., is
      prevalent in barley growing regions worldwide. A population of 118 doubled
      haploid (DH) lines developed from a cross between barley cultivars 'Rika' and
      'Kombar' were used to evaluate resistance to NTNB due to their differential
      reaction to various isolates of P. teres f. teres. Rika was resistant to P. teres
      f. teres isolate 15A and susceptible to isolate 6A. Conversely, Kombar was
      resistant to 6A, but susceptible to 15A. A progeny isolate of a 15A x 6A cross
      identified as 15A x 6A#4 was virulent on both parental lines. The Rika/Kombar
      (RK) DH population was evaluated for disease reactions to the three isolates.
      Isolate 15A induced a resistant:susceptible ratio of 78:40 (R:S) whereas isolate
      6A induced a resistant:susceptible ratio of 40:78. All but two lines had opposite
      disease reactions indicating two major resistance genes linked in repulsion.
      Progeny isolate 15A x 6A#4 showed a resistant:susceptible ratio of 1:117 with the
      one resistant line also being the single line that was resistant to both 15A and
      6A. An RK F(2) population segregated in a 1:3 (R:S) ratio for both 15A and 6A
      indicating that resistance is recessive. Molecular markers were used to identify
      a region on chromosome 6H that harbors the two NTNB resistance genes. This work
      shows that multiple NTNB resistance genes exist at the locus on chromosome 6H,
      and the recombinant DH line harboring the resistance alleles from both parents
      will be useful for the development of NTNB-resistant barley germplasm.

PMID- 18712342
TI  - A major QTL for durable leaf rust resistance widely exploited in durum wheat
      breeding programs maps on the distal region of chromosome arm 7BL.
AB  - A recombinant inbred line (RIL) population and a set of advanced lines from
      multiple crosses were used to investigate the leaf rust (Puccinia triticina
      Eriks.) resistance carried by the durum wheat cultivar Creso and its derivatives
      (Colosseo and Plinio). One hundred seventy-six RILs from the cross Colosseo x
      Lloyd were tested under artificial rust inoculation in the field. The response at
      the seedling stage was also investigated. A major QTL (QLr.ubo-7B.2) for leaf
      rust resistance controlling both the seedling and the adult open field based
      response was mapped on 7BL, with the favourable allele inherited from Colosseo.
      QLr.ubo-7B.2 showed R2 and LOD peak values for the area under disease progress
      curve (AUDPC) equal to 72.9% and 44.5, respectively. The presence and location of
      QLr.ubo-7B.2 was validated by a linkage disequilibrium-based test using two-year
      field data of 62 advanced lines from 21 crosses with Creso, Colosseo or Plinio as
      resistance donors. QLr.ubo-7B.2 maps in a gene-dense region (7BL10-0.78-1.00)
      carrying several genes/QTLs in wheat and barley for resistance to rusts and other
      fungal diseases.

PMID- 18712343
TI  - Molecular cytogenetic characterization of alien introgressions with gene Fhb3 for
      resistance to Fusarium head blight disease of wheat.
AB  - Fusarium head blight (FHB) resistance was identified in the alien species Leymus
      racemosus, and wheat-Leymus introgression lines with FHB resistance were reported
      previously. Detailed molecular cytogenetic analysis of alien introgressions T01,
      T09, and T14 and the mapping of Fhb3, a new gene for FHB resistance, are reported
      here. The introgression line T09 had an unknown wheat-Leymus translocation
      chromosome. A total of 36 RFLP markers selected from the seven homoeologous
      groups of wheat were used to characterize T09 and determine the homoeologous
      relationship of the introgressed Leymus chromosome with wheat. Only short arm
      markers for group 7 detected Leymus-specific fragments in T09, whereas 7AS
      specific RFLP fragments were missing. C-banding and genomic in situ hybridization
      results indicated that T09 has a compensating Robertsonian translocation
      T7AL.7Lr#1S involving the long arm of wheat chromosome 7A and the short arm of
      Leymus chromosome 7Lr#1 substituting for chromosome arm 7AS of wheat.
      Introgression lines T01 (2n = 44) and T14 (2n = 44) each had two pairs of
      independent translocation chromosomes. T01 had T4BS.4BL-7Lr#1S + T4BL
      7Lr#1S.5Lr#1S. T14 had T6BS.6BL-7Lr#1S + T6BL.5Lr#1S. These translocations were
      recovered in the progeny of the irradiated line Lr#1 (T5Lr#1S.7Lr#1S). The three
      translocation lines, T01, T09, and T14, and the disomic addition 7Lr#1 were
      consistently resistant to FHB in greenhouse point-inoculation experiments,
      whereas the disomic addition 5Lr#1 was susceptible. The data indicated that at
      least one novel FHB resistance gene from Leymus, designated Fhb3, resides in the
      distal region of the short arm of chromosome 7Lr#1, because the resistant
      translocation lines share a common distal segment of 7Lr#1S. Three PCR-based
      markers, BE586744-STS, BE404728-STS, and BE586111-STS, specific for 7Lr#1S were
      developed to expedite marker-assisted selection in breeding programs.

PMID- 18712344
TI  - Association of variants of the TCF7L2 gene with increases in the risk of type 2
      diabetes and the proinsulin:insulin ratio in the Spanish population.
AB  - AIMS/HYPOTHESIS: The gene encoding transcription factor 7-like 2 (TCF7L2) has
      been related to type 2 diabetes in multiple ethnic groups. Here, we investigate
      whether three single nucleotide polymorphisms (SNPs) in the TCF7L2 gene are
      associated with an impaired proinsulin:insulin ratio. METHODS: In this study we
      examined the associations between SNPs rs7901695, rs7903146 and rs12255372 in the
      TCF7L2 gene and metabolic variables affecting type 2 diabetes in a population
      based study of 706 unrelated individuals (47% men and 53% women; aged 35-74
      years) from the province of Segovia in central Spain (Castille), including 180
      individuals with type 2 diabetes. RESULTS: The minor allele frequency of
      rs7901695, rs7903146 and rs12255372 was significantly higher in diabetic patients
      compared with that in non-diabetic individuals. The T (minor) allele of the
      variant rs7903146 was significantly associated with a greater OR for type 2
      diabetes adjusted for age, sex and BMI in logistic regression analysis: OR 1.29
      (95% CI 1.06-1.57, p = 0.01). This risk allele was also associated with an
      increased proinsulin:insulin ratio after OGTT. Similar results were obtained for
      the other TCF7L2 SNPs. CONCLUSIONS/INTERPRETATION: Our results provide further
      evidence supporting the belief that the TCF7L2 gene is a major determinant of
      type 2 diabetes risk in Spain, as in other southern European populations. The
      association with increased proinsulin:insulin ratio after an OGTT suggests that
      TCF7L2 might be involved in insulin synthesis and processing.

PMID- 18712345
TI  - Plasma NEFA storage in adipose tissue in the postprandial state: sex-related and
      regional differences.
AB  - AIMS/HYPOTHESIS: We recently reported that a small fraction of circulating NEFA
      is stored through direct uptake in subcutaneous fat in postabsorptive humans in
      vivo and that this pathway may favour lower-body fat distribution in women. Here,
      we examined sex-related and regional differences in storage of plasma NEFA in
      subcutaneous adipose tissue during postprandial conditions. METHODS: At 1 h after
      lunch, men and women of normal weight received an intravenous bolus of
      approximately 1.66 MBq [1-(14)C]oleate followed by timed subcutaneous fat
      biopsies. The preceding breakfast was either a normal- or high-fat meal; the high
      fat breakfast was used to create postprandial oleate concentrations in the
      postabsorptive range. RESULTS: Storage of the NEFA tracer in adipose tissue
      (dpm/g lipid) was greater in women; in both sexes abdominal fat stored tracer
      more avidly than femoral fat. A greater fraction of the administered tracer was
      stored in whole body subcutaneous fat of women than in that of men (27 +/- 3 vs 8
      +/- 1%, respectively, p < 0.0001). No significant differences in tracer storage
      were observed between participants consuming the high- vs normal-fat breakfast.
      CONCLUSIONS/INTERPRETATION: Postprandial NEFA storage in subcutaneous fat through
      direct uptake accounts for approximately 25% of NEFA disposal in women, but for
      <10% in men in a wide range of circulating NEFA concentrations. It is greater in
      the upper- than lower-body subcutaneous fat, favouring upper-body fat
      accumulation in both sexes.

PMID- 18712346
TI  - Mediterranean diet in type 2 diabetes.

PMID- 18712347
TI  - Maximizing rates of empiric appropriate antibiotic therapy with minimized use of
      broad-spectrum agents: are surveillance cultures the key?

PMID- 18712348
TI  - Previous endotracheal aspirate allows guiding the initial treatment of ventilator
      associated pneumonia.
AB  - OBJECTIVES: Any delay in adequate antibiotic treatment compromises the outcome of
      ventilator-associated pneumonia (VAP). However, the diagnosis and optimal
      treatment of VAP remain a challenge for intensivists. We assessed the potential
      impact of using results of routine weekly endotracheal aspirate (EA) cultures to
      guide initial antibiotic treatment for VAP. DESIGN AND SETTING: Retrospective
      analysis of prospectively collected data in a medical-surgical intensive care
      unit (ICU) of a university hospital. PATIENTS AND METHODS: We studied 113 VAP
      episodes and evaluated the concordance between the latest EA and the broncho
      alveolar lavage (BAL). We stratified patients into three groups: concordant EA
      BAL (concordant group), discordant EA-BAL (discordant group) and EA not performed
      group. We then compared the adequacy of the antibiotic prescribed initially and
      outcomes between the three groups. MEASUREMENTS AND MAIN RESULTS: Ninety
      assessable EA-BAL samples were evaluated. When guided by EA, the initial
      antibiotic regimen was adequate in 85% of situations, a proportion significantly
      superior (P < 0.05) to that resulting from application of the ATS guidelines
      (73%). When clinicians did not have a pre-VAP EA to guide their treatment (EA not
      performed group), only 61% of treatments were adequate. No significant difference
      was observed between the three groups for length of mechanical ventilation,
      length of ICU stay, nonpulmonary nosocomial infections and mortality. CONCLUSION:
      Once-a-week routine quantitative EA cultures may help to improve the adequacy of
      empiric antibiotic therapy for VAP.

PMID- 18712349
TI  - Screening for resistant gram-negative microorganisms to guide empiric therapy of
      subsequent infection.
AB  - OBJECTIVE: To define the potential of resistant gram-negative colonization
      surveillance to predict etiology of subsequent infection and improve adequacy of
      empiric antimicrobial treatment. DESIGN: Retrospective cohort study. SETTING: A
      mixed medical-surgical six-bed intensive care unit (ICU), from November 2003 to
      December 2006. PATIENTS: All patients having at least one episode of ventilator
      associated pneumonia (VAP) or bloodstream infection (BSI) caused by a resistant
      gram-negative pathogen during the study period. INTERVENTIONS: Colonization
      surveillance of the respiratory tract and gastrointestinal tract was
      systematically performed in all ICU patients. Tracheal aspirates were obtained
      twice weekly and rectal swabs once weekly. Both tracheal and rectal samples were
      cultured in antibiotic-enriched media (containing ceftazidime, ciprofloxacin,
      imipenem or piperacillin/tazobactam), to focus on resistant gram-negative
      pathogen isolation. MEASUREMENTS AND RESULTS: Colonization concordance between
      resistant, gram-negative pathogens of infectious episodes and previous, recent
      (<or=7 days) colonization of the respiratory and gastrointestinal tract was
      determined, based on species identity and antimicrobial susceptibility.
      Concordance was 82% in VAP and 86% in BSI cases and was further confirmed by
      molecular testing of 15 randomly selected cases by REP-PCR. Previous colonization
      had high sensitivity and specificity in VAP, but was less specific in BSI cases.
      Knowledge of previous colonization improved the rate of adequate empiric
      antimicrobial treatment (91 vs. 40% in VAP and 86 vs. 50% in BSI cases, P <
      0.05). CONCLUSIONS: Colonization surveillance for resistant gram-negative
      microorganisms is predictive of subsequent infection etiology and can improve
      empiric antimicrobial treatment adequacy in a critical care setting.

PMID- 18712350
TI  - Physiological effects of noninvasive positive ventilation during acute moderate
      hypercapnic respiratory insufficiency in children.
AB  - INTRODUCTION: A prospective physiological study was performed in 12 paediatric
      patients with acute moderate hypercapnic respiratory insufficiency to assess the
      ability of noninvasive positive pressure ventilation (NPPV) to unload the
      respiratory muscles and improve gas exchange. MATERIALS AND METHODS: Breathing
      pattern, gas exchange, and inspiratory muscle effort were measured during
      spontaneous breathing and NPPV. RESULTS: NPPV was associated with a significant
      improvement in breathing pattern, gas exchange and respiratory muscle output.
      Tidal volume and minute ventilation increased by 33 and 17%, and oesophageal and
      diaphragmatic pressure time product decreased by 49 and 56%, respectively. This
      improvement in alveolar ventilation translated into a reduction in mean partial
      pressure in carbon dioxide from 48 to 40 mmHg (P = 0.01) and in respiratory rate
      from 48 to 41 breaths/min (P = 0.01). No difference between a clinical setting
      and a physiological setting of NPPV was observed. In conclusion, this study shows
      that NPPV is able to unload the respiratory muscles and improve clinical outcome
      in young patients admitted to the paediatric intensive care unit for acute
      moderate hypercapnic respiratory insufficiency.

PMID- 18712351
TI  - The times, they are a changing.

PMID- 18712352
TI  - Endoscopic calcaneoplasty combined with Achilles tendon repair.
AB  - Endoscopic calcaneoplasty is a minimally invasive technique for resection of
      inflamed retrocalcaneal bursa as well as the posterosuperior part of the
      calcaneus. A relative contra-indication for this technique is a tear of the
      Achilles tendon. In this report, we describe the treatment of a patient with
      Haglund's deformity associated with a tear of the Achilles tendon. Both the
      lesions are treated endoscopically. The technique is described and the pitfalls
      are discussed.

PMID- 18712353
TI  - Effect of arthroscopic partial meniscectomy on the function of quadriceps
      femoris.
AB  - The purpose of this study was to investigate the functional characteristics of
      the quadriceps femoris (QF) muscle group after the effect of presurgery disuse,
      surgery, and postsurgery disuse using surface electromyography and muscle
      functional magnetic resonance imaging (mfMRI). A total of 20 individuals (11 men
      and nine women) who underwent arthroscopic knee surgery participated in this
      study. Maximum voluntary contraction (MVC) of the QF muscle group was measured in
      the legs that received surgery and those that did not. To acquire the functional
      properties of the QF muscle group, electromyographic (EMG) activity during
      repetitive dynamic knee extension exercises (five sets of ten repetitions; load
      30% MVC) and mfMRI before and after the exercises were obtained. EMG activity was
      evaluated in three phases depending on the knee joint angle: concentric and
      eccentric phases (Con/Ecc), concentric (Con) phase only, and eccentric (Ecc)
      phase only. The mean MVC of the legs that received surgery was significantly
      lower (22%) than that of the legs that did not. Regarding the EMG activity during
      the Con/Ecc and Con phases, there were significant leg and set effects but no
      significant leg-by-set interactions; however, during the Ecc phase, there was a
      significant set effect. Regarding changes in the mfMRI signal, leg and exercise
      had significant effects, but there was no significant leg-by-exercise
      interaction. These results suggest that presurgery disuse, partial meniscectomy,
      and postsurgery disuse induce dysfunction of the QF muscle group that is
      dependent on a decrease in MVC. Thus, these patients need maximal muscle-force
      improvement for effective rehabilitation after surgery.

PMID- 18712354
TI  - Histological evaluation of the healing potential of the anterior cruciate
      ligament by means of augmented and non-augmented repair: an in vivo animal study.
AB  - The purpose of this animal study was to investigate the healing potential of the
      anterior cruciate ligament following transaction at the femoral end, by means of
      both the augmented and the nonaugmented primary repair, focusing on the
      histological changes during a 12-month postoperative observation period with
      respect to necrosis and the loss of normal structures during the healing period.
      Twenty sheep were randomly assigned to nonaugmented primary ACL repair, or to
      augmented ACL repair using a polyethylene terephthalate (PET) band. At 2, 6, 16,
      26 and 52 weeks postoperatively four sheep out of each group were sacrificed.
      Histological healing was achieved after 16 weeks for the augmented repair group
      and after 26 weeks for the nonaugmented repair group. The main difference between
      the two techniques was that the PET augmentation device protected the ligament
      from necrosis and ligamentization. In this group a consistently normal ligament
      was seen histologically during the entire postoperative observation period. The
      nonaugmented repaired ACLs underwent the processes of necrosis and
      ligamentization.

PMID- 18712355
TI  - Isokinetic quadriceps and hamstring muscle strength and knee function 5 years
      after anterior cruciate ligament reconstruction: comparison between bone-patellar
      tendon-bone and hamstring tendon autografts.
AB  - Existing clinical studies have not proven which graft is to be preferred in
      anterior cruciate ligament (ACL) reconstruction. In recent years, bone-patellar
      tendon-bone and hamstring tendons have been the most frequently used graft types.
      Muscle strength deficit is one of the consequences after ACL reconstruction. The
      aim of this study was to evaluate possible differences in hamstring and
      quadriceps muscle strength and knee function 5 years after ACL reconstruction
      between the BPTB and the STG groups. The study group consisted of 288 patients
      (132 women, 156 men) with a unilateral ACL rupture who had received a BPTB (175
      patients) or STG (113 patients) ACL reconstruction. Lower extremity concentric
      isokinetic peak extension and flexion torques were assessed at the angular
      velocities of 60 degrees /s and 180 degrees /s. The International Knee
      Documentation Committee (IKDC), the Tegner activity level, the Lysholm knee and
      the Kujala patellofemoral scores were also collected. Isokinetic quadriceps peak
      torque (percentage of the contralateral side) was 3.9% higher in the STG group
      than in the BPTB group at the velocity of 60 degrees /s and 3.2% higher at the
      velocity of 180 degrees /s and the isokinetic hamstring peak torque 2% higher in
      the BPTB group than in the STG group at the velocity of 60 degrees /s and 2.5%
      higher at the velocity of 180 degrees /s. In both groups the subjects had weaker
      quadriceps and hamstring muscle strength in the injured extremity compared with
      the uninjured one. In the single-leg hop test (according to the IKDC
      recommendations) there was a statistically significant difference (P = 0.040)
      between the groups. In the STG group, 68% of the patients had the single-leg hop
      ratio (injured vs. uninjured extremity) > or =90%, 31% of the patients 75-89% and
      1% of the patients <75%, while in the BPTB group the corresponding percentages
      were 72, 21 and 7%. However, no statistically significant differences in clinical
      outcome were found between the groups as determined by the IKDC, Tegner activity
      level, Lysholm knee and Kujala patellofemoral scores.

PMID- 18712356
TI  - Lateral ankle fracture with missed proximal tibiofibular joint instability
      (Maisonneuve injury).
AB  - We present a case of a soccer player who sustained a lateral ankle fracture and
      the associated proximal anterolateral tibiofibular joint instability (Maisonneuve
      injury) was overlooked. After a non-contact injury the (incomplete) diagnosis of
      a lateral malleolar fracture (type Weber B, AO 44-B1) was made and the patient
      was surgically treated with open reduction and internal fixation including a
      distal syndesmosis screw. After removal of the syndesmosis screw (six weeks after
      surgery) the patient suffered from activity-related pain around the fibular head.
      After thorough clinical and radiologic examination, temporary screw transfixation
      of the fibular head and capsular repair under meticulous fluoroscopic control of
      fibular rotation helped to restore patient's sport activity level. This case
      report emphasizes the importance of precise clinical examination for detection of
      a proximal tibiofibular joint instability. Restoration of a well functioning and
      stable proximal tibiofibular joint may be difficult to achieve in previously
      operated and missed instabilities.

PMID- 18712357
TI  - A biomechanical study of the meniscofemoral ligaments and their contribution to
      contact pressure reduction in the knee.
AB  - The aim of this study was to test the hypothesis that the meniscofemoral
      ligaments (MFLs) of the human knee assist the lateral meniscal function in
      reducing tibiofemoral contact pressure. Five human cadaveric knee joints were
      loaded in axial compression in extension using a 4-degree of freedom rig in a
      universal materials testing machine. Contact pressures pre- and post-sectioning
      of the MFLs were measured using pressure sensitive film. Sectioning the MFLs
      increased the contact pressure significantly in the joints for two of the four
      measures. In addition to their known function in assisting the posterior cruciate
      ligament (PCL) to resist tibiofemoral posterior drawer, the MFLs also have a
      significant role in reducing contact stresses in the lateral compartment. Their
      retention in PCL and meniscal surgery is therefore to be advised.

PMID- 18712358
TI  - The correlation of correction magnitude and tibial slope changes following open
      wedge high tibial osteotomy.
AB  - We investigated whether there is a correlation between coronal plane correction
      magnitude and tibial slope in patients treated with medial open wedge high tibial
      osteotomy (OWHTO) and also measured changes in patellar height. Thirty-four knees
      treated with for varus deformities were retrospectively reviewed and the follow
      up period of the patients was averaged 24.1 months. Preoperative and
      postoperative measurements of the Hospital for Special Surgery (HSS) score,
      Insall-Salvati index, posterior tibial slope angle, mechanical axis deviation,
      proximal medial tibial angle (PMTA) was used to determine. All patients had a
      significant increase in their HSS score postoperatively (P < 0.0001). There was
      no significant correlation between the differences in patellar heights (P =
      0.368). The mechanical axis deviation was altered by a mean of 25.5 +/- 10.9 mm
      and the difference was statistically significant (P < 0.05). The mean posterior
      tibial slope angle on preoperative radiographs was 9.0 +/- 5.1 degrees ; on
      postoperative radiographs it was 11.7 +/- 5.7 degrees and the difference was
      statistically significant (P < 0.007). Seventeen knees (50%) demonstrated
      postoperative posterior tibial slope angle increases; 7 knees (21%) had a
      decrease in this angle, while 10 knees (29%) showed no change. Statistical
      analyses revealed that the mechanical axis deviation was not correlated with
      change in tibial slope (P = 0.837). Although we could not find a correlation
      between tibial slope change and the amount of coronal correction, 50% of our
      patients demonstrated increased tibial slope.

PMID- 18712359
TI  - Clinical and structural results of partial supraspinatus tears treated by
      subacromial decompression without repair.
AB  - Patients with primary impingement and articular sided partial tears of the
      supraspinatus are often treated by subacromial decompression without repair, if
      the extent of the tear is estimated to be below 50% of tendon thickness. It has
      been questioned whether repair of these cuff lesions is necessary, because these
      tears could progress to full thickness tears with deteriorating clinical results.
      Our hypothesis was that subacromial decompression without repair of the
      supraspinatus tendon leads to significant clinical improvement for patients with
      grade I and II articular sided tears without progression to a full thickness tear
      on a regular basis. 46 consecutive patients (av. Age 59.2 years, range 33-76.6
      years) were retrospectively reviewed after an average follow up of 50.3 months
      (36-86 months). 26 patients (43.5%) had a grade I tear according to Ellman, which
      was left alone, 20 patients suffered from a grade II tear, which was debrided.
      Clinical outcome was assessed with the ASES Score and ultrasound evaluation was
      performed on all patients to detect possible progression to a full thickness
      tear. The average ASES Score significantly improved from 37.4 to 86.6 points (p <
      0.0001). The mean postoperative Constant Score was 87.6 points. Only three
      patients (6.5%) progressed to a full thickness tear detectable on ultrasound
      examination. Only one of these patients had a poor result with an ASES Score of
      35 points, the other two were very satisfied and had an ASES score above 90
      points. 8 patients showed no more signs of partial tearing on ultrasound and
      these patients had an average ASES Score of 93.1 points. Overall clinical outcome
      was rated excellent in 35 cases (76.1%), good in 5 (10.9%), average in 2 (4.3%)
      and poor in 4 (8.7%). Our results indicate that good and excellent results can be
      achieved mid- to long term by acromioplasty without repair of the rotator cuff in
      articular sided partial tears grade I and II. These results reach almost 95% of
      the value of a healthy shoulder. A better result on ultrasound examination was
      associated with a superior clinical outcome, while progression to a full
      thickness tear was rare.

PMID- 18712360
TI  - Acanthamoeba castellanii an environmental host for Shigella dysenteriae and
      Shigella sonnei.
AB  - The interaction between Shigella dysenteriae or Shigella sonnei and Acanthamoeba
      castellanii was studied by viable counts, gentamicin assay and electron
      microscopy. The result showed that Shigella dysenteriae or Shigella sonnei grew
      and survived in the presence of amoebae for more than 3 weeks. Gentamicin assay
      showed that the Shigella were viable inside the Acanthamoeba castellanii which
      was confirmed by electron microscopy that showed the Shigella localized in the
      cytoplasm of the Acanthamoeba castellanii. In conclusion, the relationship
      between Shigella dysenteriae and Shigella sonnei with Acanthamoeba castellanii is
      symbiotic, and accordingly free-living amoebae may serve as a transmission
      reservoir for Shigella in water.

PMID- 18712361
TI  - Effects on haemolytic activity of single proline substitutions in the Bordetella
      pertussis CyaA pore-forming fragment.
AB  - The recombinant Bordetella pertussis CyaA pore-forming (CyaA-PF) fragment was
      previously shown to be expressed separately in Escherichia coli as a soluble
      precursor that can be in vivo palmitoylated to exert haemolytic activity. In this
      study, PCR-based mutagenesis was employed to investigate the contributions to
      haemolysis of five predicted helices within the N-terminal hydrophobic region of
      the CyaA-PF fragment. Single proline substitutions were made for alanine near the
      centre of each predicted helix as a means of disrupting local secondary
      structure. All mutant proteins were over-expressed in E. coli as a 126-kDa
      soluble protein at levels comparable to the wild-type. Marked reductions in
      haemolytic activity against sheep erythrocytes of mutants, A510P, A538P, A583P
      and A687P pertaining to the putative helices 1(500-522), 2(529-550), 3(571-593)
      and 5(678-698), respectively, were observed. However, a slight decrease in
      haemolytic activity was found for the proline replacement in the predicted helix
      4(602-627) (A616P). MALDI-TOF-MS and LC-MS-MS analyses verified the
      palmitoylation at Lys983 of all five mutants as identical to that of the CyaA-PF
      wild-type protein, indicating that toxin modification via this acylation was not
      affected by the mutations. Altogether, these results suggest that structural
      integrity of the predicted helices 1, 2, 3 and 5, but not helix 4, is important
      for haemolytic activity, particularly for the putative transmembrane helices 2
      and 3 that might conceivably be involved in pore formation of the CyaA-PF
      fragment.

PMID- 18712362
TI  - Early preclinical studies of discriminable sedative and hallucinogenic drug
      effects.
AB  - RATIONALE: One important technique in behavioral pharmacology is to train
      laboratory animals to discriminate between a psychoactive drug effect and a
      nondrug condition. Tests with different drugs have identified several categories
      of drugs that have different discriminable effects. OBJECTIVES: The two authors
      describe and discuss the early research on discriminable effects of sedative and
      hallucinogenic drugs and their acquaintance with each other at Yale University
      prior to their early and frequent publications on discriminable drug effects.
      Herb Barry studied sedative drugs primarily and Jim Appel studied hallucinogenic
      drugs. RESULTS: Sedative drugs include ethyl alcohol, barbiturates, and
      benzodiazepines. Their discriminable effects are largely attributable to the
      activation of an inhibitory neurotransmitter, gamma-amino butyric acid. Alcohol
      has the most pervasive effect in accordance with the high dose required to alter
      behavior. Hallucinogenic drugs include lysergic acid diethylamide and mescaline.
      They increase the activity of the neurotransmitter 5-hydroxytryptamine and,
      perhaps, dopamine in the central nervous system (CNS). In spite of their
      relatively low concentrations in the brain, both of these neurotransmitters have
      many important behavioral effects. CONCLUSIONS: Various sedative drugs cause a
      discriminable decrease in the function of the CNS. Different types of sedatives
      can be discriminated from each other. Indole and phenylethylamine hallucinogens
      have potent discriminative stimulus properties, which are related to the actions
      of biogenic amine neurotransmitters in the CNS.

PMID- 18712365
TI  - Development and characterization of new rat monoclonal antibodies for
      procalcitonin.
AB  - The development of selective and sensitive biological recognition elements, e.g.,
      antibodies, for the detection of relevant blood markers is a great challenge in
      the field of biosensors. In this context, five new rat monoclonal antibodies
      (mAbs) for procalcitonin (PCT), a marker for bacterial infection and sepsis, were
      developed and characterized. One mAb, PROC1 3G3, was used as capture antibody.
      Four mAbs, PROC4 6C6, PROC4 6B2, PROC4 1G3, and PROC4 1D6, were used as detection
      mAbs, either as Protein G-purified or as biotinylated mAbs. A surface plasmon
      resonance (SPR) biosensor was used to characterize the antigen-antibody
      biomolecular interactions. The capture mAb (PROC1 3G3) has an equilibrium
      dissociation constant (K (D)) of 3.42 x 10(-8) M. All four detection mAbs (PROC4
      6C6, PROC4 6B2, PROC4 1G3, and PROC4 1D6) are of high affinity (K (A) = 2.81-6.11
      x 10(8) M(-1); K (D) = 1.64-3.56 x 10(-9) M) and have moderate dissociation rate
      constants (k (d) = 1.70-2.40 x 10(-3) s(-1)). Four different sandwich enzyme
      linked immunosorbent assays (ELISAs) with standards of human recombinant (hr)
      PCT, using PROC1 3G3 as capture mAb and PROC4 mAbs as detection mAbs,
      respectively, led to highly specific determinations of PCT without cross
      reactivities to calcitonin and katacalcin. The lower limits of quantification
      (LLOQ) for hrPCT (in 40 mM phosphate-buffered saline (PBS), pH 7.6) with these
      assays ranged from 2.3 to 12.8 microg L(-1). In addition, sandwich ELISAs were
      set up with biotinylated PROC4 mAbs, and with hrPCT in 4% human serum albumin
      (diluted 1:10 in 40 mM PBS, including 1:5 (v/v) LowCross Buffer(R)). The LLOQs of
      these sandwich assays ranged from 4.1 to 6.0 microg L(-1) and were thus much
      closer together for the different assays. With the latter assay setup (PROC1 3G3
      as capture mAb, PROC4 6C6-biotin as detection mAb) a first collection of five
      serum samples was determined (healthy volunteers, unspiked, and spiked). Recovery
      rates for the spiked samples ranged from 98.3 to 115.7%. The newly developed anti
      PCT mAbs should find broad applications in immunosensors for point-of-care
      diagnostics of sepsis and systemic inflammation processes.

PMID- 18712363
TI  - Increased particulate phosphodiesterase 4 in the prefrontal cortex supports 5-HT4
      receptor-induced improvement of object recognition memory in the rat.
AB  - RATIONALE: Serotonin receptors (5-HT4Rs) are critical to both short-term and long
      term memory processes. These receptors mainly trigger the cyclic adenosine
      monophosphate (cAMP)/protein kinase A signaling pathway, which is regulated by
      cAMP phosphodiesterases (PDEs). OBJECTIVES: We investigated the mechanisms
      underlying the effect of the selective activation of 5-HT4R on information
      acquisition in an object recognition memory task and the putative regulation of
      PDE. MATERIALS AND METHODS: The effect of RS 67333 (1 mg/kg, intraperitoneally
      [i.p.], injected 30 min before the sample phase) was examined at different delay
      intervals in an object recognition task in Sprague-Dawley rats. After the testing
      trial, PDE activity of brain regions implicated in this task was assayed.
      RESULTS: RS 67333-treated rats spent more time exploring the novel object after a
      15-min (P < 0.001) or 4-h delay (P < 0.01) but not after a 24-h delay, whereas
      control animals showed no preference for the novel object for delays greater than
      15 min. We characterized the specific patterns and kinetic properties of PDE in
      the prefrontal and perirhinal cortices as well as in the hippocampus. We
      demonstrated that particulate PDE activities increase in both the prefrontal
      cortex and hippocampus following 5-HT4R stimulation. In the prefrontal cortex,
      PDE4 activities support the RS 67333-induced modification of PDE activities,
      whereas in the hippocampus, all cAMP-PDE activities varied. In contrast,
      particulate PDE variation in the hippocampus was not found to support improvement
      of recognition memory after a 4-h delay. CONCLUSIONS: We provide evidence that
      the increase in particulate PDE4 activity in the prefrontal cortex supports the 5
      HT4R-induced increase in information acquisition.

PMID- 18712366
TI  - The transformation of phenyltin species during sample preparation of biological
      tissues using multi-isotope spike SSID-GC-ICPMS.
AB  - A multi-isotope spike species-specific isotope dilution (MI-SSID) calibration
      strategy in connection with gas chromatography-inductively coupled plasma mass
      spectrometry was applied to evaluate different extraction procedures for the
      speciation analysis of phenyltin (PhT) compounds in biological materials: mussel
      tissue BCR CRM-477 and fish tissue NIES-11. Three different isotope-enriched PhT
      compounds, (118)Sn-enriched monophenyltin (MPhT), (122)Sn-enriched diphenyltin
      (DPhT), and (124)Sn-enriched triphenyltin (TPhT), were used for the preparation
      of spikes to follow and correct for six possible interconversion reactions
      between PhT species that can take place in a sample. The acidity of the
      extractant, the presence of complexing reagents, and the use of ultrasonic or
      microwave agitation were found to affect the degradation of PhT compounds. No
      formation of PhTs through phenylation and negligible degradation of MPhT to
      inorganic tin were observed under the conditions investigated. The degree of
      degradation increased with increased acidity of extractant and when
      ultrasonication or microwave agitation was used. Under relatively mild extraction
      conditions, the degradation factors for DPhT and TPhT in the two reference
      materials studied were found, using MI-SSID, to be between 10 and 55% and 2 and
      10%, respectively. Using the degradation factors, we calculated corrected
      concentration values for the organotin species. When microwave extraction at high
      power output was used, hydrogen radicals were formed that can enhance the
      degradation of DPhT and TPhT. The hydrogen radicals were trapped using N-tert
      butyl-alpha-phenylnitrone and detected by electron spin resonance spectrometry.
      The effect of different extraction parameters on the degradation of PhT compounds
      in biological samples is discussed.

PMID- 18712364
TI  - Neurochemical, behavioral, and physiological effects of pharmacologically
      enhanced serotonin levels in serotonin transporter (SERT)-deficient mice.
AB  - RATIONALE: Serotonin transporter (SERT) knockout (-/-) mice have an altered
      phenotype in adulthood, including high baseline anxiety and depressive-like
      behaviors, associated with increased baseline extracellular serotonin levels
      throughout life. OBJECTIVES: To examine the effects of increases in serotonin
      following the administration of the serotonin precursor 5-hydroxy-L-tryptophan (5
      HTP) in SERT wild-type (+/+), heterozygous (+/-), and -/- mice. RESULTS: 5-HTP
      increased serotonin in all five brain areas examined with approximately 2- to 5
      fold increases in SERT+/+ and +/- mice, and with greater 4.5- to 11.7-fold
      increases in SERT-/- mice. Behaviorally, 5-HTP induced exaggerated serotonin
      syndrome behaviors in SERT-/-, mice with similar effects in male and female mice.
      Studies suggest promiscuous serotonin uptake by the dopamine transporter (DAT) in
      SERT-/- mice, and here, the DAT blocker GBR 12909 enhanced 5-HTP-induced
      behaviors in SERT-/- mice. Physiologically, 5-HTP induced exaggerated temperature
      effects in SERT-deficient mice. The 5-HT1A antagonist WAY 100635 decreased 5-HTP
      induced hypothermia in SERT+/+ and +/- mice with no effect in SERT-/- mice,
      whereas the 5-HT7 antagonist SB 269970 decreased this exaggerated response in
      SERT-/- mice only. WAY 100635 and SB 269970 together completely blocked 5-HTP
      induced hypothermia in SERT+/- and -/- mice. CONCLUSIONS: These studies
      demonstrate that SERT-/- mice have exaggerated neurochemical, behavioral, and
      physiological responses to further increases in serotonin, and provide the first
      evidence of intact 5-HT7 receptor function in SERT-/- mice, with interesting
      interactions between 5-HT1A and 5-HT7 receptors. As roles for 5-HT7 receptors in
      anxiety and depression were recently established, the current findings have
      implications for understanding the high anxiety and depressive-like phenotype of
      SERT-deficient mice.

PMID- 18712367
TI  - Direct and simultaneous profiling of epoxyeicosatrienoic acid enantiomers by
      capillary tandem column chiral-phase liquid chromatography with dual online
      photodiode array and tandem mass spectrometric detection.
AB  - Despite first evidence for the cytochrome P450-mediated enantioselective
      biosynthesis and activity of cis-epoxyeicosatrienoic acids (EETs), as yet little
      is known about the stereospecifity of EET generation and physiology, because the
      existing chiral methods are time consuming, labor intensive, and not sensitive
      enough. We present a method for highly sensitive, direct, and simultaneous chiral
      analysis of all eight EET enantiomers consisting of (i) solid-phase extraction,
      (ii) reversed-phase high-performance liquid chromatographic purification followed
      by (iii) consecutive regio- and enantiomeric separation of the four underivatized
      EET regioisomers within one chromatographic run employing capillary tandem column
      chiral-phase liquid chromatography with (iv) reliable dual online photodiode
      array and gentle electrospray ionization tandem mass spectrometric identification
      and quantitation of the eluting optical antipodes. This one-step, simple,
      expeditious, and highly sensitive measurement allows profiling of all eight EET
      enantiomers at once, thus avoiding substance loss and enabling high sample
      throughput. Limits of quantification in the low picogram range were achieved by
      the use of capillary columns with typical high quantitative sensitivity instead
      of conventional columns with low chromatographic signal intensity employed by
      previous methods. Application to tissue homogenates demonstrated the suitability
      of this approach for routine and reliable "enantioprofiling" of free endogenous
      EETs, i.e., EETs not esterified into cellular membrane phospholipids, typically
      occurring at very low concentrations. The technique can readily be employed for
      preparative purification of enantiomers in the microgram range using large-inner
      diameter columns.

PMID- 18712369
TI  - Grasp cueing and joint attention.
AB  - We studied how two different hand posture cues affect joint attention in normal
      observers. Visual targets appeared over lateralized objects, with different
      delays after centrally presented hand postures. Attention was cued by either hand
      direction or the congruency between hand aperture and object size. Participants
      pressed a button when they detected a target. Direction cues alone facilitated
      target detection following short delays but aperture cues alone were ineffective.
      In contrast, when hand postures combined direction and aperture cues, aperture
      congruency effects without directional congruency effects emerged and persisted,
      but only for power grips. These results suggest that parallel parameter
      specification makes joint attention mechanisms exquisitely sensitive to the
      timing and content of contextual cues.

PMID- 18712371
TI  - A study of synaptic connection between low threshold afferent fibres in common
      peroneal nerve and motoneurones in human tibialis anterior.
AB  - We have induced H-reflex responses in human tibialis anterior motor units and
      analysed the results using the classical technique, peristimulus time histogram
      (PSTH), and a new technique, peristimulus frequencygram (PSF). The PSF has
      recently been shown to be more reliable than the PSTH for indicating the synaptic
      connections on motoneurones, and therefore we wished to examine the differences
      between the two analysis methods. Experiments were conducted on eleven healthy
      subjects (7 males and 4 females) who did not have any known neurological
      disorder. The subject sat comfortably on a dental chair and the common peroneal
      nerve was stimulated. In each experiment, about 600 electrical stimuli were
      applied to the nerve randomly between 1 and 2 s. The recordings were taken with
      both by surface electromyogram (SEMG) and as single motor unit potentials. We
      found that, when a stimulus induces an H-reflex, it also generates a period of
      reduced activity (silent period) and a long latency excitation in the PSTH.
      However, the PSF records in general do not match the indications of the PSTH
      records. For example, when the PSTH indicated existence of a silent period
      immediately following the H-reflex response, the discharge rate of the unit was
      in fact higher than the prestimulus rate. On the contrary, during the PSTH
      illustrated long latency excitatory response, the discharge rate was lower than
      the prestimulus rate. Our findings suggest that PSF gives significantly different
      results compared with the PSTH in determining the synaptic connection of the low
      threshold muscle afferents to the motoneurones. While PSTH indicated that there
      was a silent period immediately after the H-reflex, the PSF demonstrated that the
      silent period was actually a continuation of the net excitatory effect and not a
      genuine inhibition since the small number of action potentials occured during
      this period displayed higher discharge rates than the prestimulus level.
      Furthermore, the long latency excitation, as it was indicated in the PSTH; was
      actually a net inhibitory effect since the large number of spikes that occured
      during that period had lower discharge rates than the prestimulus average. In the
      lights of the recent brain slice findings and completely different results
      obtained using the two analysis techniques, we suggest that the PSF analysis
      should be used along with the PSTH to illustrate the net synaptic connection
      between peripheral receptors and motoneurones in the human nervous system.

PMID- 18712370
TI  - Incremental angular vestibulo-ocular reflex adaptation to active head rotation.
AB  - Studies on motor learning typically present a constant adaptation stimulus,
      corresponding to the desired final adaptive state. Studies of the auditory and
      optokinetic systems provide compelling evidence that neural plasticity is
      enhanced when the error signal driving adaptation is instead adjusted gradually
      throughout training. We sought to determine whether the angular vestibulo-ocular
      reflex (aVOR) may be adaptively increased using an incremental velocity error
      signal (IVE) compared with a conventional constant and large velocity-gain demand
      (x2). We compared the magnitude of aVOR gain change for these two paradigms
      across different motion contexts (active and passive). Seven individuals with
      normal vestibular function and six individuals with unilateral vestibular
      hypofunction (UVH) were exposed to the IVE and x2 ("control") aVOR demand tasks.
      Each subject participated in 10 epochs of 30 active head impulses over a 15 min
      aVOR gain increase training session separately for the IVE and x2 paradigms,
      separated by either seven days (normal subjects) or 14 days (UVH subjects). For
      both normal and UVH subjects, both paradigms led to aVOR gain increase during the
      training session. For the normal subjects, the IVE paradigm led to larger aVOR
      gain change after training compared to the x2 paradigm, for both active (mean
      17.3 +/- 4% vs. mean 7.1 +/- 9%, P = 0.029) and passive (mean 14.2 +/- 5% vs. 4.5
      +/- 8%, P = 0.018) head impulses. For subjects with UVH, IVE produced a greater
      change in aVOR gain for active head impulses (mean 18.2 +/- 9.2% vs. mean -6 +/-
      3.8%, P = 0.003). However, aVOR gains for passive head impulses were less
      consistent after IVE, with only two subjects displaying greater aVOR gain with
      this incremental paradigm. Some individuals generated compensatory saccades that
      occurred in the same direction of the deficient aVOR during either training
      paradigm. Our data suggest that the aVOR is modifiable when the velocity error
      signal is presented incrementally, and that this adaptation stimulus is
      particularly effective in the case of unilateral vestibular hypofunction. This
      has implications for programs of vestibular rehabilitation, where active head
      rotation is prescribed as a means to improve gaze stability.

PMID- 18712372
TI  - Reflexive and volitional voice fundamental frequency responses to an anticipated
      feedback pitch error.
AB  - The pitch-shift reflex is a corrective voice fundamental frequency (F0) response
      triggered by a sudden shift or "error" in auditory feedback pitch. We
      investigated how anticipating a voice pitch error affects the pitch-shift reflex
      and volitional voice F0 responses. Adults sustained the vowel/u/at a comfortable
      pitch and pressed a button to deliver a 100 cent, 100 ms auditory feedback pitch
      shift immediately or after a random delay. Pitch shift direction was either
      constant (up) or randomized (up or down). Onset anticipation often resulted in an
      anticipatory voice F0 change, but stimulus direction predictability did not
      affect the responses. When pitch error onset and direction were both anticipated,
      some participants produced an ideomotor voice F0 change that partially imitated
      the error, but they produced no apparent pitch-shift reflex. Results imply that
      when voice pitch errors are anticipated, volitional voice F0 responses may reduce
      or enhance voice F0 stability.

PMID- 18712373
TI  - Differential effect of linguistic and non-linguistic pen-holding tasks on motor
      cortex excitability.
AB  - Writing and drawing are unique human activities. They are complex high-precision
      actions, which involve not only the motor system but also various cognitive
      systems, such as attention, short-term memory, action control, and language. In
      relation to motor control, the study of writing and drawing is of great interest
      as they provide insight in the interaction between motor control processes and
      the concurrent non-motor processes. Although sharing similar motor and mechanical
      demands, writing and drawing involve different levels of linguistic/semantic load
      and thus may be associated with different modulation of motor cortical
      excitability. Here, we have used transcranial magnetic stimulation to study
      separately activation of excitatory and inhibitory mechanisms of the motor cortex
      during performance of writing and drawing acts as well as during simple pen
      squeezing task. While cortical excitatory mechanisms appeared to be saturated by
      the pure motor demands of the tasks, and thus not amenable to modulation by the
      tasks' linguistic load, variation in cortical inhibitory activity was the main
      vehicle for differential modulation of motor cortical excitability by linguistic
      demands of the tasks. The results of this study highlight the importance of
      cortical inhibitory mechanisms in the physiology of higher cognitive activities.
      They also provide further evidence that the task specific modulation of the
      excitability of the motor cortex goes beyond motor complexity of the task and is
      also dependant on associated cognitive components.

PMID- 18712374
TI  - The CT appearance of intraoral chewing gum.
AB  - When imaged, intraoral chewing gum has the potential to be misdiagnosed. Chewing
      gum has a characteristic appearance on CT: it is ovoid in shape, hyperdense, and
      has small internal locules of air. Reports have described the appearance of gum
      on radiographs and abdominal CT images; however, no reports could be found
      detailing its appearance within the mouth. This report describes the appearance
      of intraoral chewing gum as well as the properties of the gum that lead to this
      appearance. Because of the potential for misdiagnosis, screening for intraoral
      foreign bodies should be considered prior to imaging.

PMID- 18712375
TI  - Importance of sagittal MR imaging in nontraumatic femoral head osteonecrosis in
      children.
AB  - BACKGROUND: In nontraumatic femoral head osteonecrosis, characterization of
      femoral head collapse is important in staging disease progression and planning
      treatment. Few prior studies have quantitatively compared the ability of sagittal
      and coronal MR images to detect femoral head collapse. OBJECTIVE: We hypothesized
      that sagittal MR images show a greater degree and angular span of femoral head
      collapse than coronal images. MATERIALS AND METHODS: We reviewed 38 hip MRI scans
      of nontraumatic femoral head osteonecrosis from 34 pediatric patients. In both
      sagittal and coronal images, the maximal extent and angular location along with
      the angular span of the femoral head collapse were measured. Differences were
      evaluated using a paired t-test. The extent of bone and cartilage loss from the
      femoral head was evaluated. RESULTS: Sagittal MR images showed 29% maximal
      femoral head radius collapse, whereas coronal images showed 16% collapse
      (P<0.001). Sagittal images showed a larger angular span of collapse (115 degrees
      ) than coronal images (55 degrees , P<0.001). Sagittal images showed greater
      epiphyseal bone loss in the anterior than in the posterior portion (P<0.001),
      whereas coronal images did not show a significant difference in bone loss between
      the medial and lateral portion (P=0.32). CONCLUSION: Sagittal images show greater
      femoral head collapse than coronal images in nontraumatic femoral head
      osteonecrosis.

PMID- 18712376
TI  - Multidetector CT findings of splenic artery aneurysm in children with chronic
      liver disease.
AB  - BACKGROUND: Splenic artery aneurysm (SAA) is a well-known complication of chronic
      liver disease and portal hypertension in adults. The incidence of SAA in children
      undergoing selective hepatic angiography prior to liver transplantation is
      reported as 4%, but there are few systematic studies. OBJECTIVE: To investigate
      the SAAs detected by multidetector CT angiography (MDCTA) among children with
      chronic liver disease. MATERIALS AND METHODS: A total of 124 children (71 girls,
      53 boys; mean age 118 months; age range 5 days to 204 months) with chronic liver
      disease underwent MDCTA to display the vascular anatomy and any vascular
      complications during the pretransplantation period. Of these children, 23 also
      underwent coeliac angiography. The digital subtraction angiography (DSA) and
      MDCTA findings were compared. RESULTS: SAAs were detected in 13 children (10.4%);
      none was detectable by US. All patients had more than one aneurysm; ten patients
      had more than three. In all except one patient, the SAAs were located only in the
      intraparenchymal branches of the splenic artery; in one patient they were located
      in the intraparenchymal segment and in the distal third of the splenic artery.
      The mean size of the aneurysms was 6.5 mm (range 2.5-18 mm). All patients with
      aneurysms had splenomegaly and vascular collaterals. Nine of the children with
      SAAs had portal vein pathologies (two occlusions, two stenoses, five
      dilatations). A statistically significant difference existed with regard to the
      size of spleen (P < 0.05) and patient age (P < 0.05) between children with SAAs
      and children without SAAs. There was an increased risk of SAAs in patients with
      portal vein pathologies. In 19 patients without SAAs on MDCTA, no SAAs were seen
      on DSA. CONCLUSIONS: It is likely that the incidence of SAA in children with
      chronic liver disease will increase with improved survival of children with long
      standing portal hypertension and chronic liver disease. MDCTA with multiplanar
      reconstruction is a noninvasive and effective means of imaging paediatric
      patients with SAAs, especially during the peritransplantation period, which is
      considered to be a time of significant risk for SAA rupture in this patient
      population.

PMID- 18712377
TI  - Primitive neuroectodermal tumour (PNET) of the kidney: a rare renal tumour in
      adolescents with seemingly characteristic radiological features.
AB  - BACKGROUND: Primitive neuroectodermal tumours (PNETs) constitute a family of
      neoplasms of presumed neuroectodermal origin that predominantly present as bone
      or soft-tissue masses in adolescents and young adults. PNET arising in the kidney
      is rare. OBJECTIVE: To describe the radiological features in three patients with
      primary renal PNET. MATERIALS AND METHODS: The radiological features of primary
      renal PNET in three adolescent patients (age 10, 14 and 16 years) are described.
      RESULTS: Tumour thrombus extending into the renal vein and inferior vena cava was
      noted in all three patients. In addition, further tumour extension into the
      atrium was seen in two patients with extension into a pulmonary artery in one
      patient. Neural foraminal and intraspinal extension close to the origin of the
      tumour was identified in two patients. Liver, bone and lung metastases were
      identified. CONCLUSION: While rare, one should consider the diagnosis of PNET
      when encountering a renal mass with aggressive features such as inferior vena
      cava tumour thrombus, direct intraspinal invasion and distant metastasis.

PMID- 18712378
TI  - Pancreatic cystosis in a child with cystic fibrosis.

PMID- 18712379
TI  - Entrance skin dose measured with MOSFETs in children undergoing interventional
      radiology procedures.
AB  - BACKGROUND: Interventional procedures frequently employ fluoroscopy or digital
      subtraction angiography (DSA). Few studies have documented radiation doses
      received by children during these procedures. OBJECTIVE: To measure skin entrance
      dose received during common pediatric interventional procedures. MATERIALS AND
      METHODS: MOSFET dosimeters were placed to record skin doses in 143 children
      undergoing any of five procedures: 30 PICC insertions, 34 CVL/port insertions, 30
      G/GJ tube insertions, 25 sclerotherapy/vascular anomaly procedures, 24 cerebral
      angiography procedures. The highest recorded dose (HRD) from the five MOSFET
      probes was assumed to be the peak skin dose per child. HRD values were averaged
      for children within each group and correlated with patient weight, fluoroscopy
      time and number of DSA frames. RESULTS: Average HRD was 1.8 mGy for PICC
      insertions, 1.4 mGy for CVL/port insertions, 3.9 mGy for G/GJ tube insertions,
      39.1 mGy for sclerotherapy/vascular anomaly procedures, and 149.9 and 101.6 mGy
      for frontal and lateral portions of cerebral angiography procedures. These
      entrance doses corresponded to effective dose estimates in the range 0.4-3 mSv.
      There were only modest correlations between peak skin dose and fluoroscopy time,
      patient weight and DSA frames (r (2)<0.4, P < 0.01). CONCLUSION: Pediatric
      interventional procedures are associated with a wide range of doses; those at the
      higher end require careful monitoring.

PMID- 18712380
TI  - Radiological features of ingested metallic mesh earphone pieces.
AB  - Foreign body ingestion remains a frequent cause of morbidity in infants and
      children. Symptoms vary with size, shape, location and composition of the foreign
      body. Flat objects tend to rotate to the greatest diameter of the esophageal
      lumen and become oriented in the coronal plane. We report two cases of ingested
      metallic mesh earphone pieces found in the upper esophagus. The foreign bodies
      were difficult to identify on posteroanterior images, but were more easily
      visualized on the lateral images. The presentation of this clinical entity and
      the recognition of its distinctive radiological findings may prevent a delayed
      diagnosis in the future and avoid potential complications.

PMID- 18712381
TI  - Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and
      response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human
      tumour xenografts.
AB  - PURPOSE: The purpose of the study was to investigate the associations between
      uptake of (111)In-DTPA-trastuzumab, tumour HER2 density and response to
      trastuzumab (Herceptin) of human breast cancer (BC) xenografts in athymic mice.
      MATERIALS AND METHODS: The tumour uptake of (111)In-DTPA-trastuzumab in athymic
      mice bearing BC xenografts with increasing HER2 density (0 to 3+) was evaluated.
      Specific uptake ratios were established in biodistribution (SUR) and imaging
      studies (ROI-SUR) using (111)In-labeled mouse IgG ((111)In-DTPA-mIgG). Further
      corrections were made for circulating radioactivity using tumour-to-blood ratios
      defined as a localization index (LI) and region-of-interest localization index
      (ROI-LI), respectively. Mice were treated with trastuzumab (Herceptin). A tumour
      growth inhibition index (TGI) was calculated and relative TGIs calculated by
      dividing the TGI of control by that of trastuzumab-treated mice. RESULTS: Strong,
      nonlinear associations with HER2 density were obtained if the uptake of (111)In
      DTPA-trastuzumab was corrected for nonspecific IgG localization (i.e., SUR; r (2)
      = 0.99) and circulating radioactivity (i.e., LI; r (2) = 0.87), but without these
      corrections, the association between HER2 density and tumour uptake was poor (r
      (2) = 0.22). There was a strong association between ROI-SUR and ROI-LI values and
      HER2 expression (r (2) = 0.90 and r (2) = 0.95, respectively. All tumours were
      imaged. Relative TGI values were associated with increasing uncorrected tumour
      uptake of (111)In-DTPA-trastuzumab but not always with HER2 density (i.e., MCF
      HER2-18 cells with trastuzumab-resistance). CONCLUSION: HER2 expression (0 to 3+)
      can be differentiated using (111)In-DTPA-trastuzumab, but requires correction of
      tumour uptake for nonspecific IgG localization and circulating radioactivity. The
      uncorrected uptake of (111)In-DTPA-trastuzumab was associated with tumour
      response to trastuzumab.

PMID- 18712382
TI  - Near-infrared optical imaging in glioblastoma xenograft with ligand-targeting
      alpha 3 integrin.
AB  - PURPOSE: Patients with glioblastoma usually have a very poor prognosis. Even with
      a combination of radiotherapy plus temozolomide, the median survival of these
      patients is only 14.6 months. New treatment approaches to this cancer are needed.
      Our purpose is to develop new cell surface-binding ligands for glioblastoma cells
      and use them as targeted imaging and therapeutic agents for this deadly disease.
      METHODS: One-bead one-compound combinatorial cyclic peptide libraries were
      screened with live human glioblastoma U-87MG cells. The binding affinity and
      targeting specificity of peptides identified were tested with in vitro
      experiments on cells and in vivo and ex vivo experiments on U-87MG xenograft
      mouse model. RESULTS: A cyclic peptide, LXY1, was identified and shown to be
      binding to the alpha 3 integrin of U-87MG cells with moderately high affinity (K
      (d) = 0.5 +/- 0.1 microM) and high specificity. Biotinylated LXY1, when complexed
      with streptavidin-Cy5.5 (SA-Cy5.5) conjugate, targeted both subcutaneous and
      orthotopic U-87MG xenograft implants in nude mice. The in vivo targeting
      specificity was further verified by strong inhibition of tumor uptake of LXY1
      biotin-SA-Cy5.5 complex when intravenously injecting the animals with anti-alpha
      3 integrin antibody or excess unlabeled LXY1 prior to administrating the imaging
      probe. The smaller univalent LXY1-Cy5.5 conjugate (2,279 Da) was found to have a
      faster accumulation in the U-87MG tumor and shorter retention time compared with
      the larger tetravalent LXY1-biotin-SA-Cy5.5 complex (approximately 64 kDa).
      CONCLUSIONS: Collectively, the data reveals that LXY1 has the potential to be
      developed into an effective imaging and therapeutic targeting agent for human
      glioblastoma.

PMID- 18712383
TI  - Uptake of inflammatory cell marker [11C]PK11195 into mouse atherosclerotic
      plaques.
AB  - PURPOSE: The ligand [(11)C]PK11195 binds with high affinity and selectivity to
      peripheral benzodiazepine receptor, expressed in high amounts in macrophages. In
      humans, [(11)C]PK11195 has been used successfully for the in vivo imaging of
      inflammatory processes of brain tissue. The purpose of this study was to explore
      the feasibility of [(11)C]PK11195 in imaging inflammation in the atherosclerotic
      plaques. METHODS: The presence of PK11195 binding sites in the atherosclerotic
      plaques was verified by examining the in vitro binding of [(3)H]PK11195 onto
      mouse aortic sections. Uptake of intravenously administered [(11)C]PK11195 was
      studied ex vivo in excised tissue samples and aortic sections of a LDLR/ApoB48
      atherosclerotic mice. Accumulation of the tracer was compared between the
      atherosclerotic plaques and non-atherosclerotic arterial sites by autoradiography
      and histological analyses. RESULTS: The [(3)H]PK11195 was found to bind to both
      the atherosclerotic plaques and the healthy wall. The autoradiography analysis
      revealed that the uptake of [(11)C]PK11195 to inflamed regions in plaques was
      more prominent (p = 0.011) than to non-inflamed plaque regions, but overall it
      was not higher than the uptake to the healthy vessel wall. Also, the accumulation
      of (11)C radioactivity into the aorta of the atherosclerotic mice was not
      increased compared to the healthy control mice. CONCLUSIONS: Our results indicate
      that the uptake of [(11)C]PK11195 is higher in inflamed atherosclerotic plaques
      containing a large number of inflammatory cells than in the non-inflamed plaques.
      However, the tracer uptake to other structures of the artery wall was also
      prominent and may limit the use of [(11)C]PK11195 in clinical imaging of
      atherosclerotic plaques.

PMID- 18712384
TI  - The hidden sentinel node and SPECT/CT in breast cancer patients.
AB  - PURPOSE: In a minority of breast cancer patients, lymphoscintigraphy shows no
      lymphatic drainage and 'hidden' sentinel nodes may remain undiscovered. The
      purpose of this study was to explore the additional value of the recently
      introduced hybrid SPECT/CT in breast cancer patients with axillary non
      visualisation on planar images. The role of blue dye and careful palpation of the
      axilla was evaluated in patients in whom axillary sentinel nodes remained hidden
      after SPECT/CT. METHODS: Fifteen breast cancer patients with non-visualisation on
      planar lymphoscintigraphy and 13 women with only extra-axillary sentinel nodes
      underwent SPECT/CT following late planar imaging without re-injection of the
      radiopharmaceutical. RESULTS: SPECT/CT visualised lymphatic drainage in eight of
      the 15 patients (53%) with non-visualisation on planar imaging, depicted nine of
      the 14 harvested sentinel nodes (64%) and three of five tumour-positive sentinel
      nodes. In two of the 13 patients (15%) with only extra-axillary sentinel nodes on
      their planar lymphoscintigram, SPECT/CT showed an axillary sentinel node that
      appeared to be uninvolved. Careful exploration of the axilla with the combined
      use of blue dye, a gamma probe and intra-operative palpation revealed an axillary
      sentinel node in the remaining 18 patients. SPECT/CT showed the exact anatomical
      location of all visualised sentinel nodes. CONCLUSION: SPECT/CT discovered
      'hidden' sentinel nodes in the majority of patients with non-visualisation, but
      was less valuable in patients with only extra-axillary lymphatic drainage on the
      planar images. Exploration of the axilla in patients with persistent non
      visualisation improved the identification of axillary (involved) sentinel nodes.

PMID- 18712385
TI  - The additional value of CT images interpretation in the differential diagnosis of
      benign vs. malignant primary bone lesions with 18F-FDG-PET/CT.
AB  - OBJECTIVE: To evaluate the value of a dedicated interpretation of the CT images
      in the differential diagnosis of benign vs. malignant primary bone lesions with
      18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG
      PET/CT). MATERIALS AND METHODS: In 50 consecutive patients (21 women, 29 men,
      mean age 36.9, age range 11-72) with suspected primary bone neoplasm conventional
      radiographs and 18F-FDG-PET/CT were performed. Differentiation of benign and
      malignant lesions was separately performed on conventional radiographs, PET alone
      (PET), and PET/CT with specific evaluation of the CT part. Histology served as
      the standard of reference in 46 cases, clinical, and imaging follow-up in four
      cases. RESULTS: According to the standard of reference, conventional 17 lesions
      were benign and 33 malignant. Sensitivity, specificity, and accuracy in
      assessment of malignancy was 85%, 65% and 78% for conventional radiographs, 85%,
      35% and 68% for PET alone and 91%, 77% and 86% for combined PET/CT. Median
      SUV(max) was 3.5 for benign lesions (range 1.6-8.0) and 5.7 (range 0.8-41.7) for
      malignant lesions. In eight patients with bone lesions with high FDG-uptake
      (SUV(max) >or= 2.5) dedicated CT interpretation led to the correct diagnosis of a
      benign lesion (three fibrous dysplasias, two osteomyelitis, one aneurysmatic bone
      cyst, one fibrous cortical defect, 1 phosphaturic mesenchymal tumor). In four
      patients with lesions with low FDG-uptake (SUV(max) < 2.5) dedicated CT
      interpretation led to the correct diagnosis of a malignant lesion (three
      chondrosarcomas and one leiomyosarcoma). Combined PET/CT was significantly more
      accurate in the differentiation of benign and malignant lesions than PET alone (p
      = .039). There was no significant difference between PET/CT and conventional
      radiographs (p = .625). CONCLUSION: Dedicated interpretation of the CT part
      significantly improved the performance of FDG-PET/CT in differentiation of benign
      and malignant primary bone lesions compared to PET alone. PET/CT more commonly
      differentiated benign from malignant primary bone lesions compared with
      conventional radiographs, but this difference was not significant.

PMID- 18712386
TI  - Outcome of hybrid stem fixation in osteoporotic female patients. A minimum five
      year follow-up study.
AB  - In osteoporotic patients cemented stems are usually used to achieve a good
      primary stability. However, when patients are obese or active the long-term
      survival of cemented prostheses is questioned. In these patients, a partially
      cemented stem with a hybrid fixation could be advantageous. A hybrid stem was
      retrospectively evaluated at a minimum follow-up of 60 months (mean, 75 months)
      in 58 osteoporotic women: seventeen with a body mass index (BMI) >30 (obese), 41
      with a BMI between 25 and 29.9 (overweight), and an UCLA score for activity level
      >6. At the latest follow up, the Harris hip score improved from 33.5 points
      preoperatively to 81.6 points, and the WOMAC score improved significantly. Three
      stems (4.9%) had an asymptomatic subsidence of less than 2.5 mm; no stem was
      revised. These results support the use of partially-cemented stems in heavy or
      active osteoporotic women.

PMID- 18712387
TI  - Comparison of distal and proximal centralising devices in hip arthroplasty.
AB  - Centralising devices were introduced to ensure that the prosthesis is implanted
      in a neutral position and that a cement mantle of optimal thickness is achieved
      proximally and distally. A distal centralising device (DCD) is compared with a
      proximal midshaft centralising device (PCD) to test which one provides a more
      neutral prosthetic alignment. Thirty consecutive patients undergoing
      hemiarthroplasties for femoral neck fractures were studied prospectively.
      Patients were blindly randomised to receive either a femoral component with
      proximal midshaft centraliser or distal centraliser. Both components were
      implanted following the manufacturer's protocol. Postoperative true
      anteroposterior and lateral radiographs were made to assess the stem position.
      There was no statistically significant difference between the two groups in zones
      1, 2, 3, 4, 5, 6 and 7 in both anteroposterior and lateral radiographic
      measurements. DCP and PCD both have similar centralisation and cement mantle.
      Future studies should be done to evaluate their long-term effect.

PMID- 18712389
TI  - Postoperative adjuvant chemotherapy of gastric cancer: scrutiny into the clinical
      evidence based on quality assessment of medical literature of randomized
      controlled trials.
AB  - The aim of this study was to scrutinize the evidence of adjuvant chemotherapy of
      gastric cancer by assessing the quality of the medical literature of randomized
      controlled trials (RCTs). A quality assessment (QA) scoring system was devised
      with the three parameters-control of bias, quality of report, and quality of
      design-which consisted 19 items. We searched for all the publications of the
      RCTs, from 1969 to 2007, with surgery-only arm, and their associated meta
      analyses to score. Among the 26 RCTs, quality of three articles were graded as
      (2+), 10 articles as (1+), and 13 articles as (-). Recently published studies had
      overall better quality of report, but not necessarily better quality of design.
      Three studies demonstrating a positive survival benefit of adjuvant chemotherapy
      had a grade (1+). Hierarchical clustering revealed that the 26 articles were
      grouped into three major branches associated with study quality and a multi
      institutional setting. We also obtained a statistically significant set of ten
      items (P < 0.001) that could differentiate articles of good (1-2+) and low
      quality (-) through supervised two-way hierarchical clustering. Finally, the
      level of recommendation for adjuvant chemotherapy in gastric cancer was to be a
      "B" according to the Scottish Intercollegiate Guidelines Network (SIGN) System.
      QA of medical literature should be an essential consideration for medical-related
      decision-making and the formation of evidence-based guidelines. Multidisciplinary
      discussion to develop and refine trial design is important for procuring better
      quality of RCTs of adjuvant chemotherapy of gastric cancer.

PMID- 18712390
TI  - Backward bifurcation, equilibrium and stability phenomena in a three-stage
      extended BRSV epidemic model.
AB  - In this paper we consider the phenomenon of backward bifurcation in epidemic
      modelling illustrated by an extended model for Bovine Respiratory Syncytial Virus
      (BRSV) amongst cattle. In its simplest form, backward bifurcation in epidemic
      models usually implies the existence of two subcritical endemic equilibria for
      R(0) < 1, where R(0) is the basic reproductive number, and a unique supercritical
      endemic equilibrium for R(0) > 1. In our three-stage extended model we find that
      more complex bifurcation diagrams are possible. The paper starts with a review of
      some of the previous work on backward bifurcation then describes our three-stage
      model. We give equilibrium and stability results, and also provide some
      biological motivation for the model being studied. It is shown that backward
      bifurcation can occur in the three-stage model for small b, where b is the common
      per capita birth and death rate. We are able to classify the possible bifurcation
      diagrams. Some realistic numerical examples are discussed at the end of the
      paper, both for b small and for larger values of b.

PMID- 18712391
TI  - [Clonal association of flat epithelial atypia and tubular breast cancer].
AB  - Flat epithelial atypia (FEA) of the breast has recently gained attention as a
      possible precursor lesion of highly differentiated breast cancer. Especially
      tubular carcinomas, with which FEA shares cytological features, often occur in
      close proximity to each other. To examine a possible clonal relationship, we
      analysed mutations of the highly variable region of the mitochondrial genome in a
      series of tubular carcinomas, associated FEA and normal glands. Multiple sequence
      alignment showed identical mtDNA mutations in approximately 50% of paired FEA and
      tumour samples, indicative of a clonal relationship. Our data indicate a possible
      precursor role of FEA in the development of tubular breast cancer.

PMID- 18712392
TI  - [Experience with establishment and operation of a biobank].
AB  - Tissue specimens taken in pathology for diagnostic or therapeutic interventions
      have been collected for decades, archived and used for local research projects.
      Meanwhile there is an increasing need of this material for academic and non
      academic biomedical research. Many questions in the field of translational
      research can only be addressed with a sufficient number of high quality tissue
      samples especially when combined with comprehensive clinical data. Although
      biobanks represent an indispensable basis for medical research, this might be in
      conflict with the rights of patients. Currently there are no specific regulations
      for biobanks leading to substantial legal uncertainties. However, interpretation
      of existing regulations by the National Ethics Committee or the Telematic
      Platform for Medical Research Network are important for ethical and legal
      solutions. Irrespective of future (national or European) regulations, the
      informed consent of the patients including a secure data protection concept is a
      prerequisite for establishment and operation of biobanks.

PMID- 18712393
TI  - [Testicular tumors. Predictive factors].
AB  - Patients with germ cell tumors of the testis can be given adjuvant treatment
      immediately after orchidectomy or put under surveillance with definitive
      treatment deferred until relapse. Both therapies are equally successful (success
      rate 98-99%), with surveillance alone, however, only approximately 50% of cases
      need toxic chemotherapy. The surveillance strategy is especially successful in
      patients with tumors which do not have morphological predictors of metastases. In
      seminomas the strongest predictor of metastases is tumor invasion of the rete
      testis followed by the size (O > or =4 cm) of the tumor. Vascular invasion, the
      most important predictor in non-seminomatous germ cell tumors, is less important
      in seminomas. The second most important predictor in mixed tumors is the presence
      or absence and the amount of embryonal carcinoma. The presence of teratomas and
      yolk sac tumors are considered to be predictors of a favorable course of the
      disease. The statistical impact of these markers is, however, not very strong.
      The only reliable predictor of malignancy of the gonadal stromal tumors is the
      size and tumors with a diameter > or =5 cm are always malignant.

PMID- 18712394
TI  - Ischiogluteal bursitis: a report of three cases with MR findings.
AB  - Ischiogluteal bursitis is an uncommon disorder which can be confused with
      neoplastic conditions in the buttock. Three cases of ischiogluteal bursitis in a
      57-year-old man, a 73-year-old woman and a 73-year-old man are presented. All
      patients presented with a gradually increasing, painful buttock mass. Magnetic
      resonance imaging (MRI) revealed a soft tissue mass around the ischial tuberosity
      and showed various features in the three cases. Two patients underwent excision
      of the lesion, which was histologically diagnosed as ischiogluteal bursitis. One
      patient was conservatively treated and the symptoms gradually decreased. MRI was
      very useful in diagnosing and detecting the lesion. Ischiogluteal bursitis should
      be considered in the differential diagnosis of a buttock mass.

PMID- 18712395
TI  - Polymyositis-like syndrome caused by hypothyroidism, presenting as camptocormia.
AB  - Polymyositis-like syndrome characterized by proximal muscle weakness and
      elevation of muscle enzymes may be a presenting manifestation of hypothyroidism.
      Camptocormia, which can be caused by myopathy of the paraspinal muscles, is an
      involuntary truncal flexion of the thoracolumbar spine while standing or walking.
      Among various neuromuscular disorders, hypothyroidism has not been reported in
      the literature as a cause of camptocormia. This is the first report of
      polymyositis-like syndrome with camptocormia caused by hypothyroidism.

PMID- 18712396
TI  - Clinical history for inflammatory back pain in ankylosing spondylitis: the
      sensitivity, specificity and consistency of clinical features.

PMID- 18712398
TI  - Deep sylvian meningioma: a case report and review of literature.
AB  - CASE REPORT: A 6-year-old boy presented with seizures. Computed tomography and
      magnetic resonance imaging showed a large enhancing mass in the left temporo
      parietal region. TREATMENT: He underwent left temporo-parietal craniotomy and
      total excision of the lesion. At surgery, there was no dural attachment, and the
      tumor was mainly in the posterior part of left sylvian fissure. The biopsy was
      reported as WHO grade I meningioma. OUTCOME: At 4-year follow-up, he was
      asymptomatic, and there was no tumor recurrence.

PMID- 18712397
TI  - Repair process in spontaneous intradural dissecting aneurysms in children: report
      of eight patients and review of the literature.
AB  - OBJECTIVE: The objective of this study is to present a series of eight pediatric
      patients (less than 16 years old) with complete spontaneous thrombosis of
      spontaneous intradural dissecting aneurysms. MATERIAL AND METHODS: Since 1989,
      eight consecutive patients in whom the cerebral aneurysms (four in middle
      cerebral arteries, one in posterior cerebral artery, three in basilar arteries)
      were found complete spontaneous thrombosis on follow-up MRI/MRA or conventional
      angiography. Patient histories and angiographic features were retrospectively
      reviewed. RESULTS: Complete thrombosis of aneurysms in between first few days to
      7 months was found in eight out of 1,587 patients (0.5%) in this recent series.
      Aneurysm repair was related to multivariate processes. Headache (50%), vomiting,
      and hemiplegia (37.5%) were common presenting symptoms. Partial or total
      resolution of the symptoms in a few months was often seen. Associated parent
      artery occlusions (50%) were also observed. CONCLUSION: Spontaneous resolution of
      intradural dissecting aneurysm with or without parent artery occlusion is not
      uncommon even in the pediatric population. Aneurysm repair is a dynamic and
      multifaceted entity. Mural hematoma appears to be the most important factor
      promoting thrombosis and healing of the dissecting intracranial aneurysms.

PMID- 18712399
TI  - Atypical basal ganglia germinoma presenting as cerebral hemiatrophy: diagnosis
      and follow-up with 11C-methionine positron emission tomography.
AB  - OBJECTS: Some basal ganglia germinomas are difficult to diagnose in early stage
      of disease due to vague initial presentation without discernable mass lesion on
      brain imaging. We performed this study to determine the usefulness of 11C
      methionine positron emission tomography (MET PET) for the diagnosis and
      monitoring of disease activity. MATERIALS AND METHODS: MET PET was performed in
      three consecutive patients; they presented with cerebral hemiatrophy without
      definite mass lesions on brain image. The maximum standard tracer uptake values
      (max SUVs) were calculated and used for the quantitative evaluation of the
      abnormal MET uptake. A pathological diagnosis was made after stereotactic biopsy
      using MET PET/computed tomography. The max SUVs significantly decreased after
      treatment. CONCLUSION: Basal ganglia germinoma should be considered in the
      differential diagnosis of patients with progressive hemiparesis and hemiatrophy
      on magnetic resonance imaging. The MET PET was useful for diagnosis, and it can
      be valuable in evaluation of treatment effects and monitoring for tumor
      recurrence.

PMID- 18712400
TI  - An association of gastroschisis and fatal respiratory distress: does prenatal
      bile aspiration cause early-onset respiratory failure in neonates?
AB  - We present a neonate with gastroschisis and evidence of bile aspiration in utero,
      who developed severe respiratory distress that did not respond to postnatal
      intensive respiratory care. Although rare, a newborn with gastroschisis may
      develop severe respiratory distress due to bile aspiration in utero. Given the
      poor outcome in this case, we suggest a possible role for prenatal diagnosis and
      therapy.

PMID- 18712402
TI  - [Ankylosing spondylitis in Central and Eastern Europe. Cross-sectional study on
      treatment modalities, disease activity and quality of life].
AB  - OBJECTIVES: To obtain information on the profile of patients with ankylosing
      spondylitis (AS), disease activity, previous and current treatments, and the
      proportion and profile of patients treated with conventional medications but
      considered eligible for anti-tumour necrosis factor (TNF) therapy. METHODS:
      Participants were rheumatologists from seven Central and Eastern European
      countries who were considered experts in the treatment of AS and were to include
      3-5 patients who had never received anti-TNF therapy. Rheumatologists were asked
      to decide whether they considered their patients candidates for anti-TNF therapy.
      RESULTS: A total of 1506 patients were analysed. Overall, 61% of AS patients who
      had never received anti-TNF therapy until the time of the survey were considered
      candidates for anti-TNF therapy based on the clinical judgement of their
      rheumatologists. This proportion ranged from 40% in Slovakia to 84% in Romania.
      Candidates had higher levels of disease activity and functional impairment, and
      they were more likely to report a lower quality of life. Only 38% of candidates
      fulfilled the Assessment in Ankylosing Spondylitis (ASAS) recommendations with
      respect to a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of at
      least 4 combined with previous use of at least two non-steroidal anti
      inflammatory drugs, ranging from 18% in Poland to 57% in Hungary. CONCLUSION:
      More than half of AS patients currently treated with other medications may be
      eligible for anti-TNF therapy. Also, rheumatologists regarded disease activity as
      the determining factor for starting anti-TNF drugs, but their decision did not
      always fully comply with the ASAS recommendations, confirming the need for
      continued exchange among the medical community to increase awareness of the ASAS
      recommendations.

PMID- 18712403
TI  - Migration of hip revision stems into the knee joint: alternative treatment
      modalities: technical note.
AB  - We report two unusual cases of stem penetration of long shaft femoral prosthesis
      into the knee joint after revision total hip arthroplasty. In both patients, the
      protruded tip of the stem interfered with the tibial plateau and averted the knee
      joint from full range of motion. To avoid further extensive surgery, the tips of
      the femoral stem were excised using a high speed-cutter. Both patients had
      immediate improvement in range of motion postoperatively, fast and uncomplicated
      rehabilitation, immediate pain relief, and good radiological results. If this
      rare complication occurs, we recommend for a primary intervention to cut the tip
      of the stem because replacement of the prosthesis would be a long lasting and
      very exhaustive surgery for affected patients.

PMID- 18712404
TI  - Evaluation of the cytogenetic effects of (131)I preceded by recombinant human
      thyrotropin (rhTSH) in peripheral lymphocytes of Wistar rats.
AB  - The present study was carried out to investigate the cytogenetic effects of
      therapeutic exposure to radioiodine preceded by rhTSH in an animal model. Three
      groups of Wistar rats (n = 6) were used: one group was treated only with (131)I
      (11.1 MBq/animal); the other two groups received rhTSH (1.2 mug/rat of either
      Thyrogen or rhTSH-IPEN, respectively) 24 h before administration of radioiodine.
      The percentage of lymphocytes with chromosome aberrations and the average number
      of aberrations and of dicentrics per cell were determined on blood samples
      collected 24 h, 7 and 30 days after administration of (131)I. The data show that
      the treatment with radioiodine alone or associated with rhTSH resulted in a
      greater quantity of chromosome alterations in relation to basal values after 24
      h, with a gradual decline after 7 and 30 days of treatment. An increase in
      chromosome alterations was also seen after rhTSH treatment alone. Neither of the
      treatments, i.e., with (131)I alone or associated with hormone, resulted in an
      aneugenic effect or influenced the kinetics of cellular proliferation in rat
      blood lymphocytes. There was no significant difference between the cytogenetic
      effects of Thyrogen and rhTSH-IPEN treatment. These data suggest that the
      treatment with radioiodine, associated or not with rhTSH, affects to a limited
      extent a relatively small number of cells although the occurrence of late
      stochastic effects could not be discarded.

PMID- 18712405
TI  - A rapid mtDNA assay of 22 SNPs in one multiplex reaction increases the power of
      forensic testing in European Caucasians.
AB  - We have developed a multiplex mitochondrial (mtDNA) assay of 21 coding region
      single nucleotide polymorphisms (SNPs) and one control region SNP outside
      hypervariable region 1 (HVR1) and hypervariable region 2 (HVR2) that can be
      amplified in a single reverse touchdown polymerase chain reaction. Single base
      extension using the SNaPshot technique is also carried out as one multiplex.
      Besides the nine major European haplogroups (i.e. H, I, J, K, T, U, V, W, and X),
      16 additional subclades (i.e. N1, X2, X2b, U2'-4/7'-9', J/T, J1, J1c, HV, H1,
      H1a1, H1c, H3, H4, H6a, H7a H10) can be detected and classified into a
      phylogenetic mtDNA tree. By analyzing 130 Caucasoid samples from Germany, 36
      different haplotypes were found resulting in a power of discrimination of 93.2%.
      Although 49% of all samples belonged to superhaplogroup H, the most common
      haplotype, i.e., haplogroup-specific SNPs plus haplogroup unspecific SNPs, had a
      frequency of only 18%. This assay is applicable for high-throughput mtDNA
      analysis and forensic mass screening. It will give additional information to the
      common control region sequencing of HVR1 and HVR2.

PMID- 18712406
TI  - Levels of metals and organic substances in workers at a hazardous waste
      incinerator: a follow-up study.
AB  - PURPOSE: To determine the blood and urine concentrations of a number of metals
      and organic substances in workers at a hazardous waste incinerator (HWI) in
      Catalonia, Spain, 8 years after regular operations in the facility. To compare
      these concentrations with the baseline (1999) levels and with those obtained in
      previous (2000 and 2005) surveys. METHODS: The employees were divided into three
      groups according to their specific workplaces. Plasma analyses of
      hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs 28, 52, 101, 138, 153
      and 180) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), as
      well as urinary analyses of 2,4- and 2,5-dichlorophenol (DCP), 2,4,5- and 2,4,6
      trichlorophenol (TCP), pentachlorophenol (PCP) and 1-hydroxypyrene (1-HP) were
      carried out. Blood concentrations of manganese and mercury, and urinary levels of
      nickel were also determined. RESULTS: For organic compounds in plasma, the
      comparison of the current levels with those of previous surveys did not show any
      significant increase for any of the compounds analyzed. In contrast, plasma
      levels of PCBs 28, 52 and 101 were significantly lower than the respective
      baseline concentrations, while especially notable was the significant reduction
      in the levels of PCDD/Fs in plasma of plant workers, which decreased from 26.7 pg
      I-TEQ/g lipid in the baseline survey to the current 2.5 pg I-TEQ/g lipid.
      CONCLUSION: According to the results of the present study, there are no evident
      signs of occupational exposure to a number of metals and organic substances in
      the workers of the HWI.

PMID- 18712407
TI  - Vertical whole-body vibration does not increase cardiovascular stress to static
      semi-squat exercise.
AB  - The purpose of this study was to determine the effect of vertical whole-body
      vibration (WBV) on heart rate (HR), mean arterial pressure (MAP), femoral artery
      blood flow (FBF), and leg skin temperature (LSk(temp)) during static exercise.
      These parameters were examined: seated next to the WBV device (passive,
      unloaded), with feet secured onto the WBV platform (knees 90 degrees flexion) and
      while standing in a semi-squat position (static, loaded, knees 120 degrees
      flexion); both with and without WBV. Conditions involved 1 min bouts separated by
      1 min rest, repeated 15 times followed by 10 min recovery. WBV in the seated
      condition had no effect on the responses examined. The static semi-squat without
      WBV increased MAP 9 mmHg (P < 0.05) with no significant effect on HR, FBF, or
      LSk(temp). Similarly, WBV static semi-squat increased MAP 8-14 mmHg (P < 0.05),
      FBF 135-180 mL/min, and LSk(temp) 1.8-3.1 degrees C (P < 0.05). However, only the
      LSk(temp) was increased above the no-WBV semi-squat position (P < 0.05). The
      addition of WBV to repeated intermittent static semi-squats does not appear to be
      a significant cardiovascular stressor.

PMID- 18712409
TI  - The role of parenteral glutamine supplement for surgical patient perioperatively:
      result of a single center, prospective and controlled study.
AB  - BACKGROUND: We conducted a prospective and case-controlled study to evaluate the
      impact of supplement of alanyl-glutamine dipeptide (Gln) in parenteral nutrition
      on perioperative immune and nutritional changes and clinical outcomes for
      patients undergoing gastrointestinal (GI) operations. MATERIALS AND METHODS:
      During 2006, 70 patients undergoing GI surgeries were allocated equally into two
      groups. One group received regular parenteral nutrition and the other received
      the same formulation and supplemented with the Gln; the two groups were
      isonitrogenous. The infusion was started from 1 day before operation to the sixth
      day after operation for 7 days. Blood samples were collected on the morning of
      the day before the operation and on the morning 6 days after the operation and
      analyzed for immune and nutrition parameters. RESULTS: There were no differences
      between the two groups in terms of clinical characteristics, operative
      procedures, biochemistry, nutritional status, and immune status preoperatively.
      After GI surgery, significant reduction in nutritional and immune parameters were
      observed in both groups, demonstrated by significant difference of albumin, C
      reactive protein (CRP), lymphocyte count, T cell, and CD8 cell. The length of
      hospital stay is slightly longer in the control group patients, but not to
      statistical significance (16.3 +/- 21.3 versus 12.2 +/- 6.8 days, p = 0.299). In
      terms of morbidity, there was no difference between the two groups, but two
      patients in the control group had wound infection; none was noted in the Gln
      group (p = 1.0). No surgical mortality was noted in this study. CONCLUSIONS:
      Perioperative parenteral nutrition supplemented with Gln is beneficial for
      patients undergoing GI surgery. Gln supplementation significantly attenuated
      postoperative inflammation and ameliorated postoperative immunodepression as well
      as nutritional depression in GI surgery.

PMID- 18712410
TI  - Parkinson's disease influences the perioperative risk profile in surgery.
AB  - BACKGROUND AND AIMS: Aim of this study was to define the perioperative risk
      profile in surgery of patients suffering from Parkinson's disease (PD) in order
      to improve treatment options in these patients. MATERIALS AND METHODS: Over a
      period of 13 years, 51 patients suffering from Parkinson's disease treated in the
      departments of general, visceral, thoracic, vascular, and trauma surgery were
      retrospectively compared using matched-pair analysis with 51 controls not
      affected by PD. Both groups of patients were assessed regarding morbidity and
      mortality, length of treatment, and rehabilitation. RESULTS: Surgical patients
      suffering from Parkinson's disease showed an increase in risk of morbidity.
      Postoperative falls occurred more commonly (entire cohort, p < 0.03). In PD
      patients treated in the trauma surgery department, postoperative falls (p <
      0.04), postoperative stay (p < 0.03), and overall duration of treatment (p <
      0.02) were significantly longer than in patients without PD. PD patients of the
      trauma unit could be discharged home less often for ambulantory rehabilitation
      after in-patient treatment (p < 0.03). CONCLUSIONS: Concomitant Parkinson's
      disease is a significant factor of perioperative morbidity in surgical patients,
      especially of patients treated in the trauma unit. Perioperative morbidity in PD
      patients may be influenced by early diagnostic and therapeutic measures.

PMID- 18712411
TI  - Congenital dilatation of the common bile duct and pancreaticobiliary maljunction:
      clinical implications.
AB  - CLINICAL CONDITIONS AND DIAGNOSIS: Congenital dilatation of the common bile duct
      is a disease in which the extrahepatic bile duct, or both the extra and
      intrahepatic bile ducts, is dilated in various ways. Pancreaticobiliary
      maljunction is a disease in which the pancreatic duct meets the bile duct outside
      of the duodenal wall beyond the sphincter Oddi. Recently, these diseases have
      been thought to be closely related to each other but to be different
      malformations. Biliary tract carcinoma, especially bile duct carcinoma, is found
      in about 30% of patients with congenital dilatation of the bile duct. The
      concomitance of bile and pancreatic juice and their stasis in the biliary tract
      induce cellular proliferation and reproduction and stimulate genetic alterations
      in biliary epithelium, which may play an important role in carcinogenesis of the
      bile duct. THERAPEUTIC STRATEGIES: Endoscopic retrograde cholangiopancreatography
      is useful for examining pancreaticobiliary maljunction. The operation is dilated
      bile duct resection and hepaticojejunostomy, which ensure that pancreatic juice
      and bile do not mix in the bile duct. Gallbladder carcinoma develops in more than
      90% of pancreaticobiliary maljunction without bile duct dilatation.

PMID- 18712412
TI  - Muscle wasting and interleukin-6-induced atrogin-I expression in the cachectic
      Apc ( Min/+ ) mouse.
AB  - Interleukin-6 (IL-6) is necessary for cachexia in Apc ( Min/+ ) mice, but the
      mechanisms inducing this myofiber wasting have not been established. The purpose
      of this study was to examine gastrocnemius muscle wasting in the Apc ( Min/+ )
      mouse and to determine IL-6 regulated mechanisms contributing to muscle loss.
      Gastrocnemius type IIB mean fiber cross-sectional area (CSA) from Apc ( Min/+ )
      mice decreased 32% between 13 and 22 weeks of age. Apc ( Min/+ ) mice lacking IL
      6 did not have type IIB fiber atrophy, while overexpression of circulating IL-6
      exacerbated the loss of type IIB fiber CSA in Apc ( Min/+ ) mice. Muscle Atrogin
      I mRNA expression was induced at least ninefold at 18 and 22 weeks of age
      compared to 13-week-old mice. Atrogin-I gene expression was also induced by
      overexpression of circulating IL-6. These data suggest that high circulating IL-6
      levels induce type IIB fiber CSA loss in Apc ( Min/+ ) mice, and circulating IL-6
      is sufficient to regulate Atrogin-I gene expression in cachectic mice.

PMID- 18712413
TI  - Cadherin-catenin complex and transcription factor Snail-1 in spindle cell
      carcinoma of the head and neck.
AB  - Spindle cell carcinoma (SpCC) is a biphasic tumor composed of squamous cell
      carcinoma (SCC) and a malignant spindle cell component. There is mounting
      evidence that SpCC is a monoclonal neoplasm originating from a stem cell giving
      rise to both components. We tested the hypothesis that spindle cell phenotype
      might be related to the cadherin-catenin complex, which forms adherens junctions
      between cells. We analyzed the immunohistochemical expression of E- and N
      cadherin, alpha-, beta- and gamma-catenin, and Snail-1, a transcription repressor
      of E-cadherin, in 30 cases of SpCC, and 30 cases of SCC of the head and neck. In
      SpCC, cadherin and catenin expression was similar in the SCC component, whereas
      in the spindle cell component, loss of E-cadherin and neo-expression of N
      cadherin was found in 19 cases, loss of cadherins in seven, and their co
      expression in four cases. Catenin expression were altered in 18 SpCCs. Snail-1
      was found in 19 SpCC cases. In SCC, E-cadherin and catenins were expressed in all
      cases, and N-cadherin focally in five cases. Snail-1 was observed in the stroma.
      To summarize, in SpCC, there is an altered expression of the cadherin-catenin
      complex, associated with morphological transition from epithelial to spindle cell
      phenotype. These features are reminiscent of epithelial-mesenchymal transition
      (EMT). Our study thus indicates that EMT might play an important role in the
      pathogenesis of SpCC. This conclusion is further supported by our finding of
      Snail-1 expression, a potent inducer of EMT, in more than half SpCC cases.

PMID- 18712414
TI  - AMACR expression in colorectal cancer is associated with left-sided tumor
      localization.
AB  - Alpha-methylacyl-CoA racemase (AMACR) is an enzyme playing an important role in
      the beta-oxidation of branched-chain fatty acids and fatty acid derivatives.
      Altered expression levels of AMACR have been described in various cancers
      including colorectal cancer (CRC). To determine the potential prognostic impact
      of AMACR expression, we analyzed 1,315 CRC on a tissue microarray (TMA) by
      immunohistochemistry (IHC). Clinical follow-up data were available from all
      cancer patients. Positive AMACR staining was observed in 1,074 (81.7%) of the
      1,315 cases including 276 cancers with weak (21.0%) and 798 cancers with strong
      staining (60.7%). AMACR IHC was significantly associated with tumor grade, stage,
      non-mucinous phenotype, and left-sided tumor localization (p < 0.0001 each).
      AMACR positivity was observed in 65.8% of cancers from the right-sided colon, in
      73.2% of cancers from the colon transversum, in 81.1% of cancers from the colon
      descendens, and in 88.9% of the distal left-sided cancers (sigma and rectum; p <
      0.0001). However, AMACR staining results were unrelated to clinical outcome. It
      is concluded that AMACR cannot serve as a prognostic marker in CRC. We
      hypothesize that the association of AMACR expression with tumor localization may
      be related to differences in the metabolism/exposure to fatty acids occurring
      along the colon.

PMID- 18712415
TI  - Survey of canine dirofilariasis in Vojvodina, Serbia.
AB  - In 2006 and 2007, a total of 193 blood samples were collected from privately
      owned dogs housed predominantly outdoors, resident in four provinces in
      Vojvodina, Serbian Republic. Circulating microfilariae of Dirofilaria repens,
      Dirofilaria immitis and Acanthocheilonema reconditum were found in 49.2%, 7.2%
      and 2.1% of dogs, respectively. Two additional occult heartworm infections were
      revealed with an antigen test of 90 amicrofilaraemic dogs. Prevalence values were
      not influenced by sex and breed, but D. repens was significantly more prevalent
      in dogs > or =6 years old, and differences were observed between provinces. This
      is the first detailed survey on canine dirofilariasis in the continental part of
      the Balkans. Vojvodina is shown to have the northernmost limit of heartworm
      infection in the Balkan area and one of the zones in Europe with the highest
      prevalence of canine subcutaneous dirofilariasis. Chemoprophylaxis should be
      considered for resident dogs and dogs visiting this region.

PMID- 18712416
TI  - Vascular access complications in long-term pediatric hemodialysis patients.
AB  - Current data demonstrate pediatric patients who remain on hemodialysis (HD)
      therapy are more likely to be dialyzed via central venous catheters (CVCs) than
      arteriovenous grafts (AVGs) and fistulae (AVFs). We retrospectively compared
      complications and health-related quality of life (HRQOL) associated with
      different vascular access types at two large centers over a 1-year period.
      Patients included in the study were younger than 25 years of age, weighed >20 kg,
      and had received HD for at least 3 months. Thirty CVC patients and 21 AVG/AVF
      patients received a total of 2,393 and 3,506 HD treatments, respectively. The
      infectious complication rate was higher for CVC patients, who were hospitalized
      3.7 days for each 100 HD treatments versus 0.2 days for AVG/AVF patients (p <
      0.01). CVC patients also had a much higher rate of access revision, needing 2.7
      hospital days every 100 HD treatments compared with 0.2 days for AVG/AVF patients
      (p < 0.01). HRQOL scores did not differ between groups. Thus, despite similar
      HRQOL, CVCs were associated with more complications and greater morbidity when
      compared with AVG/AVFs. These findings further emphasize the need to use AVG/AVFs
      as primary HD access for pediatric patients expected to receive a long course of
      maintenance HD.

PMID- 18712418
TI  - Mechanical spinal cord compression at the apex of a kyphosis: a propos of one
      case. Review of the literature.
AB  - There are a few case reports in the literature on mechanical compressions of the
      spinal cord associated with Scheuermann's disease and the treatment is not
      codified. We describe a case of spinal cord compression at the apex of the
      kyphosis, which disappeared with the reduction of the deformity. Given the
      skeletal immaturity, anterior and posterior fusions had to be performed together
      in order to obtain a good result.

PMID- 18712419
TI  - A novel fusionless vertebral physeal device inducing spinal growth modulation for
      the correction of spinal deformities.
AB  - Current fusionless scoliosis surgical techniques span the intervertebral disc.
      This alters the spine stiffness, disc pressure equilibrium and possibly may lead
      to disc degeneration. A new fusionless physeal device was developed that locally
      modulates vertebral growth by compressing the physeal ring, while maintaining
      maximum segmental spinal mobility without spanning the intervertebral disc. This
      study's objective was to test the feasibility of the device on a small animal
      model by inducing a scoliotic deformity (inverse approach) while analyzing the
      growth modifications. This study was conducted on caudal vertebrae of 21 rats (26
      day-old) divided into 3 groups: (1) "experimental" (n = 11) with 4 instrumented
      vertebrae, (2) sham (n = 5) and (3) control (n = 5). Radiographs were taken at
      regular intervals during the 7-week experimental period. Tissues were embedded in
      methyl metacrylate (MMA), prepared by the cutting/grinding method, and then
      stained (Toluidine blue). The discs physiological alterations were qualitatively
      assessed and classified by inspection of the histological sections. A mean
      maximum Cobb angle of 30 masculine (+/-6 masculine) and a mean maximum vertebral
      wedge angle of 10 masculine (+/-3 masculine) were obtained between the 23rd and
      35th day postoperative in the subgroup that underwent a long-term response from
      the device. The sham group underwent no growth alterations when compared to the
      control group. Descriptive histological analyses of the operated segments showed
      that 69% had no alterations to the intervertebral disc. This study presents
      experimental evidence that the device induces a significant and controlled
      wedging of the vertebrae while maintaining regular flexibility. In most discs,
      there were no visible morphological alterations induced. Further analysis of the
      discs and testing of this device on a larger animal is recommended with the long
      term objective of developing an early treatment of progressive idiopathic
      scoliosis.

PMID- 18712420
TI  - The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from
      Haemophilus influenzae contains two active-site histidine residues.
AB  - The catalytic and structural properties of the H67A and H349A dapE-encoded N
      succinyl-L,L-diaminopimelic acid desuccinylase (DapE) from Haemophilus influenzae
      were investigated. On the basis of sequence alignment with the carboxypeptidase
      from Pseudomonas sp. strain RS-16, both H67 and H349 were predicted to be Zn(II)
      ligands. The H67A DapE enzyme exhibited a decreased catalytic efficiency (180
      fold) compared with wild-type (WT) DapE towards N-succinyldiaminopimelic acid. No
      catalytic activity was observed for H349A under the experimental conditions used.
      The electronic paramagnetic resonance (EPR) and electronic absorption data
      indicate that the Co(II) ion bound to H349A-DapE is analogous to that of WT DapE
      after the addition of a single Co(II) ion. The addition of 1 equiv of Co(II) to
      H67A DapE provides spectra that are very different from those of the first Co(II)
      binding site of the WT enzyme, but that are similar to those of the second
      binding site. The EPR and electronic absorption data, in conjunction with the
      kinetic data, are consistent with the assignment of H67 and H349 as active-site
      metal ligands for the DapE from H. influenzae. Furthermore, the data suggest that
      H67 is a ligand in the first metal binding site, while H349 resides in the second
      metal binding site. A three-dimensional homology structure of the DapE from H.
      influenzae was generated using the X-ray crystal structure of the DapE from
      Neisseria meningitidis as a template and superimposed on the structure of the
      aminopeptidase from Aeromonas proteolytica (AAP). This homology structure
      confirms the assignment of H67 and H349 as active-site ligands. The
      superimposition of the homology model of DapE with the dizinc(II) structure of
      AAP indicates that within 4.0 A of the Zn(II) binding sites of AAP all of the
      amino acid residues of DapE are nearly identical.

PMID- 18712422
TI  - Quality choice in a health care market: a mixed duopoly approach.
AB  - We investigate a health care market with uncertainty in a mixed duopoly, where a
      partially privatized public hospital competes against a private hospital in terms
      of quality choice. We use a simple Hotelling-type spatial competition model by
      incorporating mean-variance analysis and the framework of partial privatization.
      We show how the variance in the quality perceived by patients affects the true
      quality of medical care provided by hospitals. In addition, we show that a case
      exists in which the quality of the partially privatized hospital becomes higher
      than that of the private hospital when the patient's preference for quality is
      relatively high.

PMID- 18712421
TI  - Coordination and binding geometry of methyl-coenzyme M in the red1m state of
      methyl-coenzyme M reductase.
AB  - Methane formation in methanogenic Archaea is catalyzed by methyl-coenzyme M
      reductase (MCR) and takes place via the reduction of methyl-coenzyme M (CH3-S
      CoM) with coenzyme B (HS-CoB) to methane and the heterodisulfide CoM-S-S-CoB. MCR
      harbors the nickel porphyrinoid coenzyme F430 as a prosthetic group, which has to
      be in the Ni(I) oxidation state for the enzyme to be active. To date no
      intermediates in the catalytic cycle of MCRred1 (red for reduced Ni) have been
      identified. Here, we report a detailed characterization of MCRred1m ("m" for
      methyl-coenzyme M), which is the complex of MCRred1a ("a" for absence of
      substrate) with CH3-S-CoM. Using continuous-wave and pulse electron paramagnetic
      resonance spectroscopy in combination with selective isotope labeling (13C and
      2H) of CH3-S-CoM, it is shown that CH3-S-CoM binds in the active site of MCR such
      that its thioether sulfur is weakly coordinated to the Ni(I) of F430. The complex
      is stable until the addition of the second substrate, HS-CoB. Results from EPR
      spectroscopy, along with quantum mechanical calculations, are used to
      characterize the electronic and geometric structure of this complex, which can be
      regarded as the first intermediate in the catalytic mechanism.

PMID- 18712423
TI  - Microbial community dynamics in uranium contaminated subsurface sediments under
      biostimulated conditions with high nitrate and nickel pressure.
AB  - BACKGROUND, AIM, AND SCOPE: The subsurface at the Oak Ridge Field Research Center
      represents an extreme and diverse geochemical environment that places different
      stresses on the endogenous microbial communities, including low pH, elevated
      nitrate concentrations, and the occurrence of heavy metals and radionuclides,
      including hexavalent uranium [U(VI)]. The in situ immobilization of U(VI) in the
      aquifer can be achieved through microbial reduction to relatively insoluble
      U(IV). However, a high redox potential due to the presence of nitrate and the
      toxicity of heavy metals will impede this process. Our aim is to test
      biostimulation of the endogenous microbial communities to improve nitrate
      reduction and subsequent U(VI) reduction under conditions of elevated heavy
      metals. MATERIALS AND METHODS: Column experiments were used to test the
      possibility of using biostimulation via the addition of ethanol as a carbon
      source to improve nitrate reduction in the presence of elevated aqueous nickel.
      We subsequently analyzed the composition of the microbial communities that became
      established and their potential for U(VI) reduction and its in situ
      immobilization. RESULTS: Phylogenetic analysis revealed that the microbial
      population changed from heavy metal sensitive members of the actinobacteria,
      alpha- and gamma-proteobacteria to a community dominated by heavy metal resistant
      (nickel, cadmium, zinc, and cobalt resistant), nitrate reducing beta- and gamma
      proteobacteria, and sulfate reducing Clostridiaceae. Coincidentally, synchrotron
      X-ray absorption spectroscopy analyses indicated that the resulting redox
      conditions favored U(VI) reduction transformation to insoluble U(IV) species
      associated with soil minerals and biomass. DISCUSSION: This study shows that the
      necessary genetic information to adapt to the implemented nickel stress resides
      in the endogenous microbial population present at the Oak Ridge FRC site, which
      changed from a community generally found under oligotrophic conditions to a
      community able to withstand the stress imposed by heavy metals, while efficiently
      reducing nitrate as electron donor. Once nitrate was reduced efficient reduction
      and in situ immobilization of uranium was observed. CONCLUSIONS: This study
      provides evidence that stimulating the metabolism of the endogenous bacterial
      population at the Oak Ridge FRC site by adding ethanol, a suitable carbon source,
      results in efficient nitrate reduction under conditions of elevated nickel, and a
      decrease of the redox potential such that sulfate and iron reducing bacteria are
      able to thrive and create conditions favorable for the reduction and in situ
      immobilization of uranium. Since we have found that the remediation potential
      resides within the endogenous microbial community, we believe it will be feasible
      to conduct field tests. RECOMMENDATIONS AND PERSPECTIVES: Biostimulation of
      endogenous bacteria provides an efficient tool for the successful in situ
      remediation of mixed-waste sites, particularly those co-contaminated with heavy
      metals, nitrate and radionuclides, as found in the United States and other
      countries as environmental legacies of the nuclear age.

PMID- 18712424
TI  - Atmospheric chemistry of HFE-7000 (CF(3)CF (2)CF (2)OCH (3)) and 2,2,3,3,4,4,4
      heptafluoro-1-butanol (CF (3)CF (2)CF (2)CH (2)OH): kinetic rate coefficients and
      temperature dependence of reactions with chlorine atoms.
AB  - BACKGROUND, AIM, AND SCOPE: The adverse environmental impacts of chlorinated
      hydrocarbons on the Earth's ozone layer have focused attention on the effort to
      replace these compounds by nonchlorinated substitutes with environmental
      acceptability. Hydrofluoroethers (HFEs) and fluorinated alcohols are currently
      being introduced in many applications for this purpose. Nevertheless, the
      presence of a great number of C-F bonds drives to atmospheric long-lived
      compounds with infrared absorption features. Thus, it is necessary to improve our
      knowledge about lifetimes and global warming potentials (GWP) for these compounds
      in order to get a complete evaluation of their environmental impact. Tropospheric
      degradation is expected to be initiated mainly by OH reactions in the gas phase.
      Nevertheless, Cl atoms reaction may also be important since rate constants are
      generally larger than those of OH. In the present work, we report the results
      obtained in the study of the reactions of Cl radicals with HFE-7000
      (CF(3)CF(2)CF(2)OCH(3)) (1) and its isomer CF(3)CF(2)CF(2)CH(2)OH (2). MATERIALS
      AND METHODS: Kinetic rate coefficients with Cl atoms have been measured using the
      discharge flow tube-mass spectrometric technique at 1 Torr of total pressure. The
      reactions of these chlorofluorocarbons (CFCs) substitutes have been studied under
      pseudo-first-order kinetic conditions in excess of the fluorinated compounds over
      Cl atoms. The temperature ranges were 266-333 and 298-353 K for reactions of HFE
      7000 and CF(3)CF(2)CF(2)CH(2)OH, respectively. RESULTS: The measured room
      temperature rate constants were k(Cl+CF(3)CF(2)CF(2)OCH(3)) = (1.24 +/- 0.28) x
      10(-13) cm(3) molecule(-1) s(-1)and k(Cl+CF(3)CF(2)CF(2)CH(2)OH) = (8.35 +/-
      1.63) x 10(-13) cm(3) molecule(-1) s(-1) (errors are 2sigma + 10% to cover
      systematic errors). The Arrhenius expression for reaction 1 was k (1)(266-333 K)
      = (6.1 +/- 3.8) x 10(-13)exp[-(445 +/- 186)/T] cm(3) molecule(-1) s(-1) and k
      (2)(298-353 K) = (1.9 +/- 0.7) x 10(-12)exp[-(244 +/- 125)/T] cm(3) molecule(-1)
      s(-1) (errors are 2sigma). The reactions are reported to proceed through the
      abstraction of an H atom to form HCl and the corresponding halo-alkyl radical. At
      298 K and 1 Torr, yields on HCl of 0.95 +/- 0.38 and 0.97 +/- 0.16 (errors are
      2sigma) were obtained for CF(3)CF(2)CF(2)OCH(3) and CF(3)CF(2)CF(2)CH(2)OH,
      respectively. DISCUSSION: The obtained kinetic rate constants are related to the
      previous data in the literature, showing a good agreement taking into account the
      error limits. Comparing the obtained results at room temperature, k (1) and k
      (2), HFE-7000 is significantly less reactive than its isomer C(3)F(7)CH(2)OH. A
      similar behavior has been reported for the reactions of other fluorinated
      alcohols and their isomeric fluorinated ethers with Cl atoms. Literature data,
      together with the results reported in this work, show that, for both fluorinated
      ethers and alcohols, the kinetic rate constant may be considered as not dependent
      on the number of -CF(2)- in the perfluorinated chain. This result may be useful
      since it is possible to obtain the required physicochemical properties for a
      given application by changing the number of -CF(2)- without changes in the
      atmospheric reactivity. Furthermore, lifetimes estimations for these CFCs
      substitutes are calculated and discussed. The average estimated Cl lifetimes are
      256 and 38 years for HFE-7000 and C(3)H(7)CH(2)OH, respectively. CONCLUSIONS: The
      studied CFCs' substitutes are relatively short-lived and OH reaction constitutes
      their main reactive sink. The average contribution of Cl reactions to global
      lifetime is about 2% in both cases. Nevertheless, under local conditions as in
      the marine boundary layer, tau (Cl) values as low as 2.5 and 0.4 years for HFE
      7000 and C(3)H(7)CH(2)OH, respectively, are expected, showing that the
      contribution of Cl to the atmospheric degradation of these CFCs substitutes under
      such conditions may constitute a relevant sink. In the case of
      CF(3)CF(2)CF(2)OCH(3), significant activation energy has been measured, thus the
      use of kinetic rate coefficient only at room temperature would result in
      underestimations of lifetimes and GWPs. RECOMMENDATIONS AND PERSPECTIVES: The
      results obtained in this work may be helpful within the database used in the
      modeling studies of coastal areas. The knowledge of the atmospheric behavior and
      the structure-reactivity relationship discussed in this work may also contribute
      to the development of new environmentally acceptable chemicals. New volatile
      materials susceptible of emission to the troposphere should be subject to the
      study of their reactions with OH and Cl in the range of temperature of the
      troposphere. The knowledge of the temperature dependence of the kinetic rate
      constants, as it is now reported for the case of reactions 1 and 2, will allow
      more accurate lifetimes and related magnitudes like GWPs. Nevertheless, a better
      knowledge of the vertical Cl tropospheric distribution is still required.

PMID- 18712425
TI  - Neuregulin-1 enhances differentiation of cardiomyocytes from embryonic stem
      cells.
AB  - Neuregulin-1 (NRG-1) is a multifunctional regulator that acts through receptor
      tyrosine kinases of the epidermal growth factor (EGF/ErbB) receptor family in
      diverse tissue. ErbB receptors are expressed in developing embryoid bodies (EBs),
      and the importance of the NRG-1/ErbB signaling axis in heart development has been
      investigated, but the underlying molecular mechanism is poorly studied. NRG-1
      treatment at 100 ng/ml significantly increased the number of beating EBs of
      differentiated murine embryonic stem cells (ESCs). Furthermore, NRG-1 up
      regulated the expression of the cardiac-restricted transcription factors Nkx2.5
      and GATA-4 and factors involved in differentiated cardiac cells (alpha-MHC, beta
      MHC and alpha-actinin); NRG-1-induced increase of Nkx2.5 transcription was
      inhibited by treatment with the PI3 K inhibitor or ErbB receptor inhibitor.
      Western blot analysis confirmed that the expression of phospho-Akt in the beating
      foci was increased in the presence of NRG-1. Our results suggest that NRG-1
      promotes cardiomyocyte differentiation of ESCs and the ErbB/PI3 K/Akt signaling
      pathway is one of the underlying molecular mechanisms.

PMID- 18712426
TI  - Variation in fatty acid composition in muscle and heart tissues among species and
      populations of tropical fish in Lakes Victoria and Kyoga.
AB  - The composition of the fatty acids in muscle and heart tissue of seven fish
      species, Nile perch (Lates niloticus), Nile tilapia (Oreochromis niloticus),
      marbled lungfish (Protopterus aethiopicus), African catfish (Clarias gariepinus),
      Lake Victoria squeaker (Synodontis victoriae), Bagrus docmas, and Tilapia zilli,
      from two locations in Lake Kyoga and one location in Lake Victoria was
      chemometrically determined. The muscle tissue was very lean, with an average of
      3.4 mg total fatty acids per g tissue. The lipid level in the heart tissue was
      approximately five times higher than in the muscle tissue, with an average of
      15.5 mg total fatty acids per g tissue. The n-3/n-6 level in the muscles was 1.7
      +/- 0.7 and in the heart tissue 1.0 +/- 0.4. The muscle tissue contained an
      average of 46 mg cholesterol per 100 g, and the heart tissue contained about five
      times as much. Plasmalogens were detected in 7-8% of the amounts of total fatty
      acids in both muscle and heart tissue. The seven species had large differences (P
      < 0.05) in the fatty acid composition for both muscle and heart tissue. Within
      the species there were differences between fish from the populations in the three
      locations, although the population differences were smaller than the species
      differences. These differences appear to be controlled more closely by
      genetics/transcriptomics than by the diet.

PMID- 18712427
TI  - ECMO for cardiac rescue in a neonate with accidental amiodarone overdose.
AB  - Intravenous (IV) amiodarone hydrochloride has proven to be a very effective
      antiarrhythmic treatment option for a variety of ventricular and supraventricular
      arrhythmias in adults and paediatric patients. Amiodarone is known to have
      significant side effects and these especially include profound hypotension in
      animals and adults, vasodilatation, negative inotropic effects, and significant
      bradycardia especially when administered intravenously. Special caution is
      warranted in patients with decreased contractility and end-stage heart failure.
      We present a case of accidental amiodarone overdose in a newborn treated for
      atrial flutter resulting in cardiovascular collapse. The patient could be rescued
      by rapid initiation of VA-ECMO treatment. The patient survived without
      neurological damage.

PMID- 18712428
TI  - Acute stroke unit care and early neurological deterioration in ischemic stroke.
AB  - OBJECTIVE: To evaluate the impact that monitored acute stroke unit care may have
      on the risk of early neurological deterioration (END), and 90-day mortality and
      mortality-disability. METHODS: Non-randomized prospective study with consecutive
      patients with acute ischemic stroke (AIS) admitted to a conventional care stroke
      unit (CCSU), from May 2003 to April 2005, or to a monitored acute stroke unit
      (ASU) from May 2005 to April 2006. END was defined as an increase in the NIHSS
      score >or= 4 points in the first 72 hours after admission. RESULTS: END was
      detected in 19.6% of patients (11.2% of patients admitted to the ASU and 23.8% to
      the CCSU; p<0.0001). Patients admitted to the ASU received more treatment with
      intravenous rtPa (13.5% versus 4.2%; p<0.0001), had a shorter length of stay (9.1
      [11.0] d versus 13.1 [10.4] d; p<0.0001), lower 90-day mortality (10.2% versus
      17.3%; p=0.02), and lower mortality-disability at 90-days (28.4% versus 40.2%;
      p=0.004) than those admitted to the CCSU. Multivariable analysis showed that ASU
      admission was a protector for END (OR: 0.37; 95% CI: 0.23-0.62). On admission,
      higher NIHSS (OR: 1.06; 95% CI: 1.03-1.10), higher glycaemia (OR: 1.003; 95% CI:
      1.001-1.006), and higher systolic pressure (OR: 1.01; 95% CI: 1.002-1.017) were
      independent predictors of END. CONCLUSIONS: END prevention by ASU care might be a
      key factor contributing to better outcome and decrease of length of stay in
      patients admitted to monitored stroke units.

PMID- 18712431
TI  - Short-term effects of high-dose zoledronic acid treatment on bone mineralization
      density distribution after orthotopic liver transplantation.
AB  - Patients with "hepatic" bone disease exhibit increased fracture incidence. The
      effects on bone material properties, their changes due to orthotopic liver
      transplantation (OLT), as well as zolendronate (ZOL) treatment have not yet been
      investigated. We studied bone mineralization density distribution (BMDD) in
      paired transiliacal biopsies (at and 6 months after OLT) from patients (control
      CON n = 18, treatment group ZOL n = 21, the latter treated with i.v. ZOL at doses
      of 4 mg/month) for how bone at the material level was affected by the "hepatic"
      disease in general, as well as by OLT and ZOL in particular. (1) BMDD parameters
      at baseline reflected disturbed bone matrix mineralization in "hepatic" bone
      disease combined with low turnover. Trabecular bone displayed a decrease in mean
      and most frequent calcium concentration (Ca(MEAN) -2.9% and Ca(PEAK) -2.8%,
      respectively; both P < 0.001), increased heterogeneity of mineralization
      (Ca(WIDTH) +12.2%, P = 0.01), and increased percentage of bone areas with low
      mineralization (Ca(LOW) +32.4%, P = 0.02) compared to normal; however, there were
      no differences compared to cortical bone. (2) Six months after OLT, ZOL-treated
      trabecular bone displayed reduced Ca(LOW) (-32.0%, P = 0.047), cortical bone
      increased Ca(MEAN) (+4.2%, P = 0.009), increased Ca(PEAK) (+3.3%, P = 0.040), and
      decreased Ca(LOW) (-55.7, P = 0.038) compared to CON and increased Ca(MEAN)
      compared to baseline (+1.9, P = 0.032) without any signs of hyper- or defective
      mineralization. These changes as consequence of the antiresorptive action of ZOL
      visible already after 6 months result in beneficial effects on bone matrix
      mineralization, likely contributing to the significant decrease in fracture
      incidence observed in these patients 2 years post transplantation.

PMID- 18712432
TI  - Influence of early and late zoledronic acid administration on vertebral structure
      and strength in ovariectomized rats.
AB  - An annual infusion of zoledronic acid (ZOL) reduces fracture risk in osteoporotic
      patients. Previously, we showed that a single ZOL injection inhibited changes in
      bone microstructure and strength in rat tibiae after ovariectomy. Here, we
      determined the effects of a single ZOL injection as preventive and restorative
      treatment on the bone microstructure and strength in lumbar and caudal vertebrae
      of ovariectomized (OVX) rats. Twenty-nine female 35-week-old Wistar rats were
      divided into four groups: SHAM-OVX (n = 9), OVX (n = 5), OVX and early ZOL (n =
      8), and OVX and late ZOL (n = 7). ZOL was given once (20 microg/kg body weight
      s.c.) at OVX in the early ZOL group and 8 weeks later in the late ZOL group; rats
      were killed 16 weeks after OVX. Trabecular and cortical bone microarchitecture
      were measured in lumbar (L3) and caudal (Cd6) vertebrae using micro-computed
      tomography, and compressive mechanical properties were determined in L3
      vertebrae. Compared to SHAM-OVX, OVX rats had significantly lower BV/TV; SMI,
      Tb.N, Tb.Sp, and Conn.D tended to be deteriorated in lumbar vertebrae, while both
      ZOL groups did not differ from the SHAM-OVX group. Both ZOL groups had
      significantly higher BV/TV than OVX; the early ZOL group also had significantly
      lower SMI and higher Tb.Th. OVX tended to decrease mechanical properties, while
      early and late ZOL treatment inhibited OVX-induced degeneration. Neither OVX nor
      ZOL induced changes in the trabecular microarchitecture of caudal vertebrae. In
      summary, in adult rats a single ZOL injection inhibited OVX-induced changes in
      lumbar vertebral bone microarchitecture and strength.

PMID- 18712433
TI  - Teaching the "hybrid approach": a novel swine model of muscular ventricular
      septal defect.
AB  - This report describes a reproducible swine model for creating muscular
      ventricular septal defects (VSDs). The model not only facilitates the development
      and modification of hybrid techniques for closing muscular VSDs, but also serves
      as a teaching tool that allows operators to become accustomed to the specific
      technical requirements necessary when using the hybrid approach to perform
      periventricular VSD device closure. The authors' institutional experience using
      this novel animal model is presented.

PMID- 18712434
TI  - Declining aerobic capacity of patients with arterial and atrial switch
      procedures.
AB  - BACKGROUND: Patients with transposition of the great arteries corrected by an
      atrial switch procedure are believed to have a worse physical outcome than
      patients with an arterial switch procedure correction. This study aimed to
      compare exercise data for patients with the two surgical methods. METHODS: This
      study retrospectively analyzed exercise treadmill test results for 7- to 17-year
      old patients who underwent either an atrial switch procedure (n=45) or an
      arterial switch procedure (n=44). The results were compared with reference
      material. RESULTS: Both groups showed significantly less aerobic capacity than
      healthy subjects. The atrial switch patients achieved 69% of reference status,
      and the arterial switch patients achieved 82%. A gradual decline in exercise
      capacity with increasing age was shown for patients with atrial switch
      circulation (p<0.0001). No significant difference was found for the arterial
      switch group (p=0.319). CONCLUSIONS: Significantly less aerobic capacity was
      found in atrial and arterial switch patients than in healthy subjects. A decline
      in aerobic capacity with increasing age was found in the atrial switch patients.
      However, the small number of teenagers in the arterial switch group limits the
      ability to be conclusive. The results indicate that chronotropic incompetence may
      be one of the reasons for diminishing capacity. The decline in exercise
      performance leads the authors to recommend regular follow-up exercise testing.

PMID- 18712435
TI  - Closure of external tunnel Fontan fenestration: a novel use of the Amplatzer
      vascular plug.
AB  - BACKGROUND: Newer modifications of the Fontan operation include the external
      tunnel conduit with placement of an elongated type of fenestration. Atrial septal
      defect closure devices used traditionally to close fenestrations have short
      connecting waists with retention discs on each side. These may not be suitable
      for this type of Fontan fenestration. The length of the fenestration may not
      allow proper expansion of the retention discs on these devices. The Amplatzer
      vascular plug, a new occlusion device without a centering waist or retention
      discs designed to close vascular malformation, can be placed entirely within an
      elongated tube or vessel. METHODS: A retrospective review was used to study
      patients who underwent catheter closure of Fontan fenestration in our
      institution. Only patients whose procedure was performed after the commercial
      release of the Amplatzer vascular plug were included in the study. RESULTS: The
      vascular plug was implanted in 4 of 10 patients who underwent fenestration
      closure. The plug was successfully placed in all four patients without protrusion
      into either the systemic or pulmonary venous side of the baffle. There were no
      incidences of embolization, hemolysis, or infective endocarditis. All the
      patients experienced significant improvement in oxygen saturation. The technical
      aspects of this device are discussed as well as its safe and effective use. The
      satisfactory follow-up evaluation also is reported. CONCLUSIONS: This study
      outlines a novel use of the Amplatzer vascular plug for successful closure of
      selected Fontan fenestrations.

PMID- 18712438
TI  - Breast autoinflation with sterile pus as a marker of implant rupture: single
      stage treatment and outcome for five consecutive cases.
AB  - Augmentation mammaplasty is one of the most common aesthetic procedures
      performed. Early complications of the procedure are hematoma and infection, and
      late complications include capsular contracture and device failure or its
      displacement. Failure of saline implants is readily identifiable, whereas rupture
      of silicon gel implants can occur without symptoms due to lack of volume loss.
      Autoinflation of the breast caused by intracapsular and intraprosthetic
      collection of sterile pus has been reported. A series of five consecutive breast
      autoinflations with sterile pus is presented. All the patients presented with
      acute swelling of the breast 2-10 years after prostheses implantation.
      Intracapsular sterile pus with macroscopic shell tear was seen in four cases. In
      the remaining case, an intracapsular and intraprosthetic collection of sterile
      pus with a tear in an otherwise intact implant was seen under the microscope. All
      five cases showed no microbial growth on culture or sensitivity, and all were
      treated using a single-stage procedure. The follow-up periods ranged from 8 weeks
      to 1 year without recurrence of symptoms.

PMID- 18712436
TI  - Combined preoperative use of celecoxib and gabapentin in the management of
      postoperative pain.
AB  - BACKGROUND: In 2005 we reported a study on the efficacy of the preoperative use
      of the selective COX-2 inhibitor celecoxib (Celebrex) for reducing both
      postoperative pain and opioid requirements in patients undergoing bilateral
      subpectoral breast augmentation. Our findings showed that patients who received
      400 mg of celecoxib 30 min before surgery required significantly less
      postoperative opioid analgesics compared with those given a placebo. Gabapentin
      (Neurontin) is an agent commonly used to control neuropathic pain. Here we
      describe a prospective study assessing the efficacy of preoperative gabapentin in
      combination with celecoxib for reducing postoperative pain and opioid
      requirements in elective subpectoral breast augmentation. METHODS: One hundred
      eighteen patients were given 1200 mg of gabapentin and 400 mg of celecoxib 30-60
      min before surgery. From the day of surgery until postoperative day 5, patients
      documented any use of analgesics and recorded their degree of pain. Results were
      then compared with those of our previous study in which only celecoxib was used.
      RESULTS: The combination of gabapentin and celecoxib was found to be
      significantly superior (p < 0.001) in reducing postoperative pain and opioid
      requirements than celecoxib alone in the management of postoperative pain and
      opioid requirements. CONCLUSION: To decrease postoperative opioid requirements,
      we recommend 400 mg of celecoxib and 1200 mg of gabapentin taken 30-60 min before
      surgery by patients undergoing subpectoral breast augmentation or a comparable
      plastic surgery procedure.

PMID- 18712439
TI  - Another look at breast projection after breast reduction.
AB  - A controversy exists between vertical mammoplasty and the "traditional"
      keyhole?inferior pedicle method of breast reduction. This article examines
      factors affecting breast projection by considering the difference in concept
      between vertical mammaplasty (using the modification proposed by Hall-Findley as
      an example) and the inferior pedicle?keyhole pattern. This article is not about
      "how to do" but rather about "why" things are done in a certain way. The emphasis
      is on understanding what is done and its effects rather than on technique. The
      breast can be considered a cone. Breast projection then is the ratio between the
      nipple projection and the breast base. Two key concepts need to be considered:
      the orientation of the ellipses during excision of breast tissue in breast
      reduction and the role of the breast base?inframammary fold. Breast projection is
      not determined by the scars. After an examination of each technique, methods to
      enhance projection are discussed.

PMID- 18712440
TI  - Acquired arteriovenous malformation definition: an improper use in diagnostic
      radiology practice.

PMID- 18712441
TI  - Combined line-cross and half-sib QTL analysis in Duroc-Pietrain population.
AB  - A Duroc-Pietrain resource population was built to detect quantitative trait loci
      (QTL) that affect growth, carcass composition, and pork quality. The data were
      analyzed by applying three least-squares Mendelian models: a line-cross (LC)
      model, a half-sib (HS) model, and a combined LC and HS model (CB), which enabled
      the detection of QTL that had fixed, equal, and different allele frequencies for
      alternate breed alleles, respectively. Permutation tests were performed to
      determine 5% chromosome-wide and 5% genome-wide threshold values. A total of 40
      (137) QTL were detected at the 5% genome-wide (chromosome-wide) level for the 35
      traits analyzed. Of the 137 QTL detected, 62 were classified as the LC type (LC
      QTL), 47 as the HS type (HS-QTL), and 28 as the CB type (CB-QTL). The results
      indicate that implementation of a series of model-based framework is not only
      beneficial to detect QTL, but also provides us with a new and more robust
      interpretation from which further methodology could be developed.

PMID- 18712442
TI  - Lobomycosis in bottlenose dolphins (Tursiops truncatus) from the Indian River
      Lagoon, Florida: estimation of prevalence, temporal trends, and spatial
      distribution.
AB  - Lobomycosis (lacaziosis) is a chronic fungal disease of the skin that affects
      only dolphins and humans. Previous studies have shown a high prevalence of
      lobomycosis in bottlenose dolphins (Tursiops truncatus) from the Indian River
      Lagoon, Florida (IRL). We studied the occurrence and distribution of lobomycosis
      in the IRL using photo-identification survey data collected between 1996 and
      2006. Our objectives were to (1) determine the sensitivity and specificity of
      photo-identification for diagnosis of lobomycosis in free-ranging dolphins; (2)
      determine the spatial distribution of lobomycosis in the IRL; and (3) assess
      temporal patterns of occurrence. Photographs from 704 distinctly marked dolphins
      were reviewed for skin lesions compatible with lobomycosis. The presumptive
      diagnosis was validated by comparing the results of photographic analysis with
      physical examination and histologic examination of lesion biopsies in 102
      dolphins captured and released during a health assessment and 3 stranded
      dolphins. Twelve of 16 confirmed cases were identified previously by photography,
      a sensitivity of 75%. Among 89 dolphins without disease, all 89 were considered
      negative, a specificity of 100%. The prevalence of lobomycosis estimated from
      photographic data was 6.8% (48/704). Spatial distribution was determined by
      dividing the IRL into six segments based on hydrodynamics and geographic
      features. The prevalence ranged from <1% in the Mosquito Lagoon to 16.9% in the
      south Indian River. The incidence of the disease did not increase during the
      study period, indicating that the disease is endemic, rather than emerging. In
      summary, photo-identification is a useful tool to monitor the course of
      individual and population health for this enigmatic disease.

PMID- 18712443
TI  - Comparative innate responses of the aphid parasitoid Diaeretiella rapae to
      alkenyl glucosinolate derived isothiocyanates, nitriles, and epithionitriles.
AB  - Cruciferous plants (Brassicaceae) are characterized by the accumulation of a
      group of secondary metabolites known as glucosinolates that, following attack by
      pathogens or herbivores, may be hydrolyzed to one of a number of products
      including isothiocyanates and nitriles. Despite the range of hydrolysis products
      that may be produced, the toxicity of glucosinolates to pathogens and herbivores
      may be explained largely by the production of isothiocyanates. Isothiocyanates
      are also known to provide an indirect defense by acting as host finding cues for
      parasitoids of insect herbivores that attack crucifers. It has been speculated
      that nitriles may provide a similar indirect defense. Here, we investigate the
      olfactory perception and orientation behavior of the aphid parasitoid
      Diaeretiella rapae, to a range of alkenylglucosinolate hydrolysis products,
      including isothiocyanates, nitriles, and epithionitriles. Electroantennogram
      responses indicated peripheral odor perception in D. rapae females to all 3
      butenylglucosinolate hydrolysis products tested. By contrast, of the 2
      propenylglucosinolate hydrolysis products tested, only the isothiocyanate
      elicited significant responses. Despite showing peripheral olfactory detection of
      a range of 3-butenylglucosinolate hydrolysis products, naive females oriented
      only to the isothiocyanate. Similarly, parasitoids oriented to 3
      isothiocyanatoprop-1-ene, but not to the corresponding nitrile or epithionitrile.
      However, by rearing D. rapae either on Brassica nigra, characterized by the
      accumulation of 2-propenylglucosinolate, or Brassica rapa var rapifera,
      characterized by the accumulation of 3-butenylglucosinolate, altered the innate
      response of parasitoids to 3-isothiocyanatoprop-1-ene and 4-isothiocyanatobut-1
      ene. These results are discussed in relation to the defensive roles of
      glucosinolate hydrolysis products and the influence of the host plant on aphid
      parasitoid behavior.

PMID- 18712445
TI  - The effects of adjuvant experimental radioimmunotherapy and hyperthermic
      intraperitoneal chemotherapy on intestinal and abdominal healing after
      cytoreductive surgery for peritoneal carcinomatosis in the rat.
AB  - BACKGROUND: Cytoreductive surgery (CS) followed by hyperthermic intraperitoneal
      chemotherapy (HIPEC) results in limited survival benefit and high morbidity and
      mortality rates in patients with peritoneal carcinomatosis (PC).
      Radioimmunotherapy (RIT) after CS of experimental PC has been shown to increase
      survival and compare favorably to HIPEC. The effects of RIT and HIPEC on wound
      healing after CS need to be determined. METHODS: PC was induced by
      intraperitoneal inoculation of CC-531 colon carcinoma cells in Wag/Rij rats.
      Animals were subjected to CS and anastomotic construction only or followed by RIT
      or HIPEC. RIT consisted of 74 MBq (177)lutetium-labeled anti-CC531 antibody MG1.
      HIPEC was performed by a closed abdominal perfusion technique using mitomycin-C
      during 60 minutes. Anastomotic and abdominal wall strength measurements were
      performed 3 and 5 days after surgery. RESULTS: At day 5, bursting pressure in
      ileum and colon anastomoses in the CS + HIPEC group, but not in the CS + RIT
      group, was lower (P < .01) than in the CS group. In the CS group, the colonic
      bursting site was more often outside the true anastomotic area (8 of 12 animals)
      than in the CS + HIPEC (1 of 12) and CS + RIT (5 of 12) groups. Abdominal wall
      strength in the CS + HIPEC group was significantly (P < .01) lower, at both
      measuring points, than that in both the CS group and the CS + RIT group. There
      was no difference between the latter. CONCLUSION: As adjuvant to CS, HIPEC showed
      a decrease in anastomotic and abdominal wall wound strength in a model of PC of
      CRC, whereas RIT did not.

PMID- 18712446
TI  - Translation initiation factor 4E (eIF4E): prognostic marker and potential
      therapeutic target.

PMID- 18712448
TI  - Regional therapeutic strategies in melanoma: not just local disease control, but
      an opportunity to develop novel therapeutic strategies with potential
      implications for systemic therapy.

PMID- 18712449
TI  - Age-, race-, and ethnicity-related differences in the treatment of nonmetastatic
      rectal cancer: a patterns of care study from the national cancer data base.
AB  - BACKGROUND: Recent studies suggest that older patients and minorities are less
      likely to receive surgical and adjuvant therapy for rectal cancer. We analyzed
      the independent effect of age and race/ethnicity on treatment for rectal cancer
      controlling for comorbidity and socioeconomic status using a nationwide sample
      METHODS: We identified 35,695 patients with rectal adenocarcinoma diagnosed
      between 2003 and 2005 using the National Cancer Data Base. Comorbidity was
      calculated from medical records and administrative data. Educational level and
      income were estimated from census data. Characteristics were compared across
      groups by chi(2) tests. Odds ratios of surgical and adjuvant therapy and 95%
      confidence intervals were calculated by logistic regression. RESULTS: A total of
      51% of patients were age > or =65, 8.7% were African American, and 4.9% were
      Hispanic. Younger patients, African Americans, and Hispanics were more likely to
      present with advanced disease compared with older, white patients (P < .001). Age
      > or =65 was associated with underuse of surgery and adjuvant therapy (P < .001).
      Only 85.1% of African Americans were resected, compared with 90.7% of whites
      (adjusted odds ratio, .62; 95% confidence interval, .54-.71). Among resected
      patients, race/ethnicity had no effect on rates of sphincter preservation or
      adjuvant therapy. CONCLUSIONS: A high proportion of older patients with rectal
      cancer do not receive appropriate surgical or adjuvant therapy, even when
      controlling for comorbidity. African American patients are also less likely to
      undergo resection, but are equally likely to undergo sphincter preservation and
      adjuvant therapy compared with whites. Efforts are needed to uncover the root
      causes underlying these observations and optimize treatment of rectal cancer.

PMID- 18712450
TI  - Multivisceral resection does not affect morbidity and survival after
      cytoreductive surgery and chemoperfusion for carcinomatosis from colorectal
      cancer.
AB  - BACKGROUND: Carcinomatosis of colorectal origin is increasingly treated by
      cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CS-HIPEC).
      This procedure commonly involves multivisceral resection (MVR) with potentially
      high morbidity. We analyzed the effect of MVR on the outcome after CS-HIPEC.
      METHODS: All patients with colorectal carcinomatosis operated between June 2001
      and June 2007 were included. MVR was defined as resection of two or more organs
      (n = 35). Patients without any or with a single visceral resection formed a
      control group (n = 30). RESULTS: Sixty-five patients underwent 72 procedures. MVR
      was not strongly associated with the mortality, morbidity, reoperation, or
      readmission. Morbidity, but not mortality, was more common in patients requiring
      bowel anastomosis (36 of 51 vs. 7 of 21, P = .003). Median survival from the
      diagnosis of carcinomatosis was not significantly different between the MVR and
      controls (32.8 months vs. 20.0 months, P = .787). Similarly, the median survival
      from the time of cytoreduction was not significantly different (20.2 vs. 14.3
      months; P = .436). Independent predictors of survival in the Cox regression model
      were presence of residual disease >5 mm (hazard ratio = 4.5, P = .048), evidence
      of carcinomatosis on preoperative computed tomographic scan (6.1, P = .008), and
      initial diagnosis of cancer as systemic (2.6, P = .049). MVR had no statistically
      significant effect on survival (.441, P = .133). CONCLUSIONS: Increased risk of
      complications is associated with the number of intestinal anastomoses, but not
      with multivisceral resection in CS-HIPEC. Long-term survival is not affected by
      the number of resected organs.

PMID- 18712451
TI  - A statewide community cancer center videoconferencing program.
AB  - INTRODUCTION: The multidisciplinary approach to cancer care has been established
      through a statewide videoconferencing network to discuss prospective patient
      management issues. To our knowledge this is the first report of a statewide
      community cancer center videoconferencing network in the USA. METHODS: Four of
      seven American College of Surgeons Commission on Cancer community hospitals in
      the state of Delaware agreed to participate in a statewide videoconferencing
      network. Through information technology all centers can communicate pathology and
      radiology results via visualization methodology. Information is shared on a
      weekly basis with discussion of treatment decisions and diagnostic procedures.
      The videoconferencing occurs over a 60-min period. RESULTS: All cases have been
      prospectively presented. The videoconferencing has led to an increase in National
      Cancer Institute (NCI) treatment and cancer control clinical trials accrual.
      American Society of Clinical Oncology (ASCO) guidelines and the National
      Comprehensive Cancer Center Network (NCCN) guidelines have been followed in 92%
      of case presentations as recommended by the videoconference participants.
      Physician and support personnel do not have to travel to any of the centers since
      technology allows communication amongst all participants through their own
      community cancer centers. CONCLUSION: A statewide community cancer center
      videoconferencing network has resulted in high compliance with ASCO and NCCN
      guidelines and improvement in accrual to NCI Clinical trials.

PMID- 18712452
TI  - Sleeve gastrectomy relieves steatohepatitis in high-fat-diet-induced obese rats.
AB  - BACKGROUND: Sleeve gastrectomy is thought to decrease the appetite and body
      weight of morbid obesity patients in the clinic. The purpose is to investigate
      the effect of sleeve gastrectomy on preventing steatohepatitis in morbid obesity
      rats. METHODS: Thirty rats were randomized into normal chow group (NC), high-fat
      diet group (HD), and sleeve group (SG). Rats in the SG group received sleeve
      gastrectomy operation. After operation, rats in SG and HD group received a high
      fat diet, while rats in the NC group received normal chow. Body weight was
      measured every 10 days. Thirty days later, animals were sacrificed and blood
      samples were collected to check total cholesterol, HDL, and triglyceride. Fresh
      liver sections were made and stained with Nile red and observed under a
      fluorescence microscope. RESULTS: Rats in the SG group received a moderate body
      weight decrease (191 +/- 16.2 g) in the first 10 days, while this did not happen
      in the other two groups (213 +/- 13.7 g and 243 +/- 11.9 g). At the sacrifice
      date, weight of rats in the SG group was still much lower than those in the HD
      group. Plasma triglycerol (102.3 +/- 18.6 mg/dL) and cholesterol (84.3 +/- 6.1
      mg/dL) of rats in the SG group were much lower than those in the HD group (198.5
      +/- 18.5 mg/dL, 133.9 +/- 22.0 mg/dL). Under the fluorescence microscope, adipose
      infiltration was very obvious in the liver of the HD animals, while adipose
      infiltration was not serious in the SG group. CONCLUSION: High-fat diet can
      result in obvious body weight increase and hepatic adipose infiltration compared
      with normal chow. Sleeve gastrectomy can decrease body weight even in high-fat
      diet models. Body weight control caused by sleeve gastrectomy can relieve high
      fat-diet-induced steatohepatitis in rats.

PMID- 18712453
TI  - Effects of a new allograft processing procedure on graft healing in a canine
      model: a preliminary study.
AB  - Graft healing in vivo can be affected by allograft processing. We asked whether a
      new processing technique influenced graft-host healing compared with autograft
      and a standard processing technique in a canine ulna model. We used bilateral
      intercalary allografts or autografts in the ulna of 13 skeletally mature male
      coonhounds. Each animal received two allografts, either one autograft and one
      allograft, or two autografts. At term (90 days), the graft sites were harvested.
      We assessed union with high-resolution xray imaging. Each specimen was processed
      for nondecalcified histologic analysis to assess the graft-host interface.
      Quantitative histomorphometric analysis was performed to determine spatial
      location and area of bone. Radiographic analysis, histologic analysis, and
      histomorphometric measures revealed no differences in union, mean total bone
      area, or total endosteal/intramedullary bone for the new process, standard
      process, and autografts. Our preliminary data suggest the new processing
      techniques may increase the safety of allograft transplantation without adversely
      affecting union when compared with standard processing techniques and autograft
      in a canine model.

PMID- 18712454
TI  - Posterior cruciate-retaining total knee arthroplasty for valgus osteoarthritis.
AB  - The valgus, osteoarthritic knee is challenging technically and it is unknown
      whether and how technical and implant variables influence outcomes. We therefore
      determined the influence of surgical technique of soft tissue balancing and
      patient and implant factors from 100 unselected cruciate-retaining TKAs for
      valgus osteoarthritis in patients younger than 75 years of age. From 1987 to
      1990, lateral soft tissue balancing was done with an outside-in progression in
      which the lateral collateral ligament and popliteus were typically released from
      the femur. From 1991 to 1994, an inside-out technique was use in which the
      lateral collateral ligament and/or popliteus were typically preserved. The
      minimum followup was 0.1 year (mean, 8.2 years; range, 0.1-18.2 years). Fourteen
      of 16 revisions were for wear and/or instability. Popliteus release, lateral
      collateral ligament release, or greater polyethylene shelf age increased the risk
      of revision. At 10 postoperative years, survival (end point, revision) was 89%
      (100 knees), 94% when the shelf age was less than 1 year (n = 73 knees), 97% when
      the popliteus or lateral collateral ligament was not released (n = 57 knees), and
      100% when both conditions were met (n = 39 knees). Cruciate-retaining implants
      can be successfully used in knees with any degree of valgus osteoarthritis and
      survival is improved when the surgeon preserves at least one of the structures
      providing lateral stability in flexion and uses polyethylene with a short shelf
      life. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 18712455
TI  - Less invasive TKA: extramedullary femoral reference without navigation.
AB  - Femoral intramedullary canal referencing is used by most knee arthroplasty
      systems. Fat embolism, activation of coagulation, and bleeding may occur from the
      reamed canal. The purpose of our study was to evaluate a new extramedullary
      device that relies on templated data. We randomized 100 consecutive patients
      undergoing primary total knee arthroplasty through a limited parapatellar
      approach to use of either standard intramedullary femoral instruments (IM group)
      or a new extramedullary device (EM group). The extramedullary instrument was
      calibrated using templated data obtained from a preoperative full-limb
      weightbearing anteroposterior view of the knee. In both groups, an intraoperative
      double check was performed using an extramedullary rod referring to the
      anterosuperior iliac spine. Femoral component coronal alignment was within 0
      degrees +/- 2 degrees of the mechanical axis in 84% of the IM group and 86% of
      the EM group. Sagittal alignment of the femoral component was 0 degrees +/- 2
      degrees in 78% of the IM group and 90% of the EM group. We observed no difference
      in the average operative time between the two groups. The two groups showed
      similar postoperative blood loss. Extramedullary reference with careful
      preoperative templating can be safely used during TKA. LEVEL OF EVIDENCE: Level
      II, therapeutic study. See the Guidelines for Authors for a complete description
      of levels of evidence.

PMID- 18712456
TI  - Predicting patellar failure after total knee arthroplasty.
AB  - We identified patient and surgeon factors associated with patellar component
      failure in a series of 8530 TKAs performed in 5640 patients using the same
      posterior cruciate ligament-retaining TKA with all-polyethylene patellar
      components between January 1983 and December 2003. Patellar failure was defined
      as loosening, fracture, or patellar revision. All infections were excluded.
      Statistical analysis using Kaplan-Meier and Cox regression was used to determine
      the risk of patellar failure. Followup averaged 7.0 years (range, 2-22 years).
      Patellar component loosening occurred in 4.8% of TKAs (409 knees). Patellar
      fracture was identified in 5.2% of TKA (444 knees). Twenty-five patellae were
      revised (0.3%). TKA performed with a lateral release and patients with a body
      mass index of greater than 30 kg/m(2) were at the greatest risk of patellar
      loosening and fracture, respectively. Male gender, preoperative varus alignment
      of greater than 5 degrees , and large patellar component size also predicted a
      higher risk of patellar fracture. Medial patellar component position, tibial
      component thickness of greater than 12 mm, preoperative valgus alignment of 10
      degrees or more, and preoperative flexion of 100 degrees or more predicted
      patellar loosening. An awareness of these factors that predict patellar failure
      after TKA may help determine the relative indications for TKA and influence
      surgical technique, especially when using this prosthesis. LEVEL OF EVIDENCE:
      Level IV, prognostic study. See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 18712457
TI  - Topics in global public health.
AB  - Deficiencies in the delivery of musculoskeletal trauma care in low- and middle
      income countries can be attributed to a variety of causes, all of which can be
      linked to failure of the health system to deliver the necessary services to
      prevent death and disability. As such, a "systems" approach will be required to
      improve the delivery of services. The goal of this review is to familiarize the
      orthopaedic surgeon with selected topics in public health, including health
      systems, burden of disease, disability adjusted life year (DALY), cost-effective
      analysis, and related concepts (eg, met versus unmet need, access, utilization,
      effective coverage).

PMID- 18712458
TI  - Abstracts of the 33rd Sir Peter Freyer Memorial Lecture and Surgical Symposium.
      September 5-6, 2008. Galway, Ireland.

PMID- 18712459
TI  - Quality of life evaluated by Short Form-8 in patients with rheumatoid arthritis
      who were receiving infusion of infliximab.
AB  - In this study, influences of infliximab to health-related quality of life (HRQOL)
      and active status of RA were assessed. Between 2003 and 2006, 22 patients with
      rheumatoid arthritis (RA) began receiving infusion of infliximab. Of all the
      patients, 17 patients who were followed for at least 30 weeks (102 weeks at
      maximum) after the start of infliximab were included in this study. The mean age
      was 54.6+/-10 years. HRQOL was evaluated with use of the SF-8trade mark, which is
      a simple version of the Medical Outcome Study Short Form 36. As an index of
      active status of RA, C-reactive protein (CRP), erythrocyte sedimentation rate
      (ESR), and rheumatoid factor (RF) were collected. CRP and ESR significantly
      improved at the final follow-up, but RF did not. All subscales of the SF-8 were
      significantly improved after the start of infliximab. However, there were three
      patients whose laboratory data were improved, but HRQOL was not. We should not be
      prepossessed only with laboratory data in treating patients with RA. We recommend
      that the SF-8 to evaluate HRQOL of patients with RA in busy outpatient clinics
      because it is both simple and convenient.

PMID- 18712460
TI  - Cutaneous polyarteritis nodosa in a patient with Crohn's disease.
AB  - A 19-year-old Japanese woman with a 4-year history of Crohn's disease (CD)
      developed high fever, polyarthralgia, and painful subcutaneous nodules of the
      legs. A skin biopsy showed panarteritis with fibrinoid necrosis in the deep
      dermis. Endoscopic examination showed aphthous lesions in the entire colon. She
      was diagnosed with cutaneous polyarteritis nodosa (PAN) associated with CD.
      Steroid therapy improved her symptoms. To our knowledge, this is the first
      Japanese case of cutaneous PAN associated with CD.

PMID- 18712461
TI  - Successful treatment of parainfluenza virus 3 pneumonia with oral ribavirin and
      methylprednisolone in a bone marrow transplant recipient.
AB  - We report a case of severe parainfluenza (PIV) 3 pneumonia in a hematopoietic
      stem cell transplant recipient that was successfully treated with oral ribavirin
      and methylprednisolone. A 42-year-old woman diagnosed with acute myelogenous
      leukemia (FAB M5a) in first complete remission underwent allogeneic bone marrow
      transplantation from an HLA-matched unrelated donor in May 2006. In July 2007,
      she developed PIV3 pneumonia. Her respiratory status progressively worsened and
      she required O(2) inhalation at 6 L/min. After an informed consent was obtained,
      oral ribavirin was initiated (16 mg/kg per day) for 1 week on July 31. By day 3
      of treatment, the high-grade fever had disappeared. However, it recurred after
      ribavirin was discontinued. In addition, the patient's hypoxia continued to
      worsen, requiring O(2) inhalation at 9 L/min. To suppress the inflammatory
      reaction in the lung caused by PIV3 pneumonia, intravenous methylprednisolone
      (1,000 mg once a day for 3 days) was started along with high-dose oral ribavirin
      (16 mg/kg per day) on August 11. The patient showed dramatic clinical
      improvement, and oxygen inhalation was discontinued on September 3. Our case
      suggests that with concomitant effective anti-viral treatment, corticosteroids
      may suppress host inflammatory or immune reactions that lead to respiratory
      failure.

PMID- 18712462
TI  - Chemotherapy-resistant intravascular lymphoma accompanied by ADAMTS13 inhibitor
      successfully treated with rituximab.

PMID- 18712463
TI  - Trends and correlates of HIV testing during pregnancy in racially/ethnically
      diverse insured population, 1997-2006.
AB  - OBJECTIVES: To describe the trends in human immunodeficiency virus (HIV) testing
      during pregnancy from 1997 through 2006, and the demographic, clinical, and
      health system correlates of being tested in a diverse insured population.
      METHODS: Health plan members who had one or more births at > or = 20 weeks
      gestation from January 1, 1997 through December 31, 2006 in Kaiser Permanente
      Southern California hospitals were included in this retrospective analysis. Data
      were obtained from the infants' birth certificate, and administrative and
      laboratory databases. Multiple log binomial regression analyses were used to
      generate adjusted prevalence ratios (PR) and 95% confidence interval (CI) for
      each characteristic. RESULTS: Of the 240,575 women with 302,246 pregnancies, the
      proportion tested for HIV during pregnancy increased from 77.6% in 1997 to 91.0%
      in 2006 (P (trend) < 0.0001). Compared with Hispanic women, of which 90% were
      tested, non-Hispanic white women were least likely to be tested (81.7%: PR:
      0.965; 95% CI: 0.957-0.973). Demographic characteristics negatively associated
      with HIV testing were maternal age >/=30, having more than a high school
      education, and residing in census blocks with the highest income tertile.
      Additionally, women were less likely to be tested after their first birth, if
      enrolling in prenatal care in the third trimester, or if they had a gap in
      insurance during their pregnancy. Of the 53,566 women with two sequential
      pregnancies, 78.5% were tested during both pregnancies. CONCLUSION: In an insured
      racially/ethnically patient population, the testing rate exceeded 90% in 2006.
      Achieving and sustaining these high testing levels has public health
      implications.

PMID- 18712464
TI  - Prenatal cigarette smoking and smokeless tobacco use among Alaska native and
      white women in Alaska, 1996-2003.
AB  - OBJECTIVE: To examine trends in prenatal cigarette smoking and smokeless tobacco
      use among Alaska Native (AN) and white women in Alaska. METHODS: Using 1996-2003
      data from the population-based Pregnancy Risk Assessment Monitoring System, we
      determined trends in self-reported prenatal tobacco use among AN and white women
      and used chi-square tests and multiple variable logistic regression analysis to
      identify maternal factors associated with prenatal tobacco use. RESULTS: Over the
      study period, prevalence of any tobacco use during pregnancy declined by 27%
      among AN women (from 55.8 to 40.9%) (P < 0.0001) and by 17% among white women
      (from 18.8 to 15.6%) (P < 0.0001). In 2003, among AN women the prevalence of self
      reported smokeless tobacco use was 16.9%, cigarette smoking was 25.7%, and any
      tobacco use was 40.9%; corresponding values for white women were 0.4, 15.0, and
      15.6%, respectively. Western Alaska had the highest prevalence of tobacco use.
      CONCLUSION: The prevalence of tobacco use decreased between 1996 and 2003, but
      remained higher among AN women than white women, especially for smokeless
      tobacco. Support for cessation interventions targeting pregnant women should be
      made a public health priority in Alaska.

PMID- 18712467
TI  - Changes in the timing of sexual initiation among young Muslim and Christian women
      in Nigeria.
AB  - Sexual initiation during adolescence has important demographic and health
      consequences for a population, yet no systematic analysis of changes in the
      timing of sexual initiation has been conducted in Nigeria. Two rounds of national
      surveys conducted in 1990 and 2003 were used to examine changes in the timing of
      sexual initiation among female adolescents in Nigeria. Multivariate survival
      analysis using Cox proportional hazards models was used to assess changes in the
      risk of sexual initiation and to identify the correlates of first sex. Contrary
      to what has been reported in several Nigerian studies, there was no decline in
      age at first sex among Christian adolescents. Age at first sex did not change
      significantly for Christian adolescents, although premarital sex appears to have
      increased-primarily due to an increase in the age at marriage. Age at first sex
      did increase among Muslim women. Premarital sex remained low among Muslim women.
      A number of socioeconomic variables were associated with the timing of sexual
      initiation. Weekly exposure to the mass media was associated with earlier sexual
      initiation. The degree to which an environment was liberal or restrictive was a
      key determinant of the timing of sexual initiation in Nigeria. The findings also
      illustrate the important role of socioeconomic factors in determining the timing
      of sexual initiation in Nigeria. As secondary education increases in Northern
      Nigeria, additional increases in the age at sexual debut are likely among Muslim
      women. The study raises concerns about the influence of the mass media on the
      timing of first sex in Nigeria. The evidence of an absence of changes in the
      timing of sexual initiation among Christian women in more than a decade implies
      that programs which aim to delay the timing of sexual initiation in Southern
      Nigeria may have limited success. With age at marriage already high among
      Christian women, programs that focus on abstinence until marriage may also be
      pursuing an approach with limited chances of success.

PMID- 18712468
TI  - Sex differences in personality traits and gender-related occupational preferences
      across 53 nations: testing evolutionary and social-environmental theories.
AB  - Using data from over 200,000 participants from 53 nations, I examined the cross
      cultural consistency of sex differences for four traits: extraversion,
      agreeableness, neuroticism, and male-versus-female-typical occupational
      preferences. Across nations, men and women differed significantly on all four
      traits (mean ds = -.15, -.56, -.41, and 1.40, respectively, with negative values
      indicating women scoring higher). The strongest evidence for sex differences in
      SDs was for extraversion (women more variable) and for agreeableness (men more
      variable). United Nations indices of gender equality and economic development
      were associated with larger sex differences in agreeableness, but not with sex
      differences in other traits. Gender equality and economic development were
      negatively associated with mean national levels of neuroticism, suggesting that
      economic stress was associated with higher neuroticism. Regression analyses
      explored the power of sex, gender equality, and their interaction to predict
      men's and women's 106 national trait means for each of the four traits. Only sex
      predicted means for all four traits, and sex predicted trait means much more
      strongly than did gender equality or the interaction between sex and gender
      equality. These results suggest that biological factors may contribute to sex
      differences in personality and that culture plays a negligible to small role in
      moderating sex differences in personality.

PMID- 18712466
TI  - Brief report: atypical social cognition and social behaviours in autism spectrum
      disorder: a different way of processing rather than an impairment.
AB  - A central question to autism research is whether autism is largely the result of
      an impairment in social cognition and/or motivation or the result of a more
      general processing difference. This review discusses problems with the "social
      deficit" model of autism spectrum disorder (ASD). It is suggested that superior
      attention to low-level perceptual information potentially coupled with decreased
      attention to global information may provide a more comprehensive explanation for
      atypical social behaviours in ASD. This processing style may reflect increased
      activation of occipital-temporal regions and reduced functional (and possibly
      anatomical) connectivity. It is concluded that atypical social behaviours in ASD
      are more likely to be a consequence reflective of a general processing difference
      than impairment in social cognition and/or motivation.

PMID- 18712469
TI  - Body image satisfaction in heterosexual, gay, and lesbian adults.
AB  - Does the prevalence and degree of body dissatisfaction differ among heterosexual
      and homosexual men and women? Some theorists have suggested that, compared to
      their heterosexual peers, gay men are at greater risk for body dissatisfaction
      and lesbians at lower risk. Past studies examining this issue have generally
      relied on small samples recruited from gay or lesbian groups. Further, these
      studies have sometimes produced conflicting results, particularly for comparisons
      of lesbian and heterosexual women. In the present research, we compared body
      satisfaction and comfort with one's body during sexual activity among lesbian
      women, gay men, heterosexual women, and heterosexual men through two large online
      studies (Ns = 2,512 and 54,865). Compared to all other groups, heterosexual men
      reported more positive evaluations of their appearance, less preoccupation with
      their weight, more positive effects of their body image on their quality of life
      and the quality of their sex life, more comfort wearing a swimsuit in public, and
      greater willingness to reveal aspects of their body to their partner during
      sexual activity. Few significant differences were found among gay men, lesbian
      women, and heterosexual women. Many gay men (42%) reported that their feelings
      about their body had negative effects on the quality of their sex life, as did
      some lesbian women (27%), heterosexual women (30%), and heterosexual men (22%).
      Overall, the findings supported the hypothesis that gay men are at greater risk
      than heterosexual men for experiencing body dissatisfaction. There was little
      evidence that lesbian women experience greater body satisfaction than
      heterosexual women.

PMID- 18712470
TI  - Does consideration of Medicare use affect VA evaluations of treatment for new
      episodes of depression?
AB  - This report evaluates whether consideration of out-of-system use affects Veterans
      Affairs (VA) health system assessments of depression treatment. We measured
      effective medication management and optimal practitioner contacts among veterans
      whose VA data indicated a new episode of depression. Among 3,567 VA patients who
      were Medicare age-eligible, VA data indicated that 69% received recommended
      antidepressant coverage and 9% received recommended practitioner contacts. After
      including Medicare data, 295 patients (8%) no longer met inclusion criteria.
      Among the remainder, 3% received Medicare depression treatment and 0.5% were re
      classified as having recommended contacts. Medicare use does not substantially
      supplement VA depression treatment.

PMID- 18712471
TI  - Empathy and social perspective taking in children with Attention
      Deficit/Hyperactivity Disorder.
AB  - This study explored empathy and social perspective taking in 8 to 12 year old
      children with and without Attention-Deficit/Hyperactivity Disorder (ADHD). The
      sample comprised 92 children, 50 with a diagnosis of ADHD and 42 typically
      developing comparison children. Although children with ADHD were rated by their
      parents as less empathic than children without ADHD, this difference was
      accounted for by co-occurring oppositional and conduct problems among children in
      the ADHD sample. Children with ADHD used lower levels of social perspective
      taking coordination in their definition of problems, identification of feelings,
      and evaluation of outcomes than children without ADHD, and these differences
      persisted after the role of language abilities, intelligence and oppositional and
      conduct problems were taken into account. Girls were more empathic and had higher
      overall social perspective taking scores than boys. Implications for research and
      practice are discussed.

PMID- 18712473
TI  - The variants BRCA1 IVS6-1G>A and BRCA2 IVS15+1G>A lead to aberrant splicing of
      the transcripts.
AB  - The majority of BRCA1 and BRCA2 deleterious mutations and variants of unknown
      significance have been identified in genomic DNA and their effects at the mRNA
      level have not been reported. Our aim was to ascertain the pathological effect of
      the BRCA1 IVS6-1G>A (c. 302-1G>A) and the BRCA2 IVS15+1G>A (c. 7617+1G>A)
      variants detected in Spanish breast/ovarian cancer families. Sequencing of cDNA
      from the BRCA1 IVS6-1G>A allele revealed an inappropriate splicing of exon 7. The
      analysis of the BRCA2 IVS15+1G>A allele showed the skipping of exon 15. Both
      alterations predicted the appearance of premature stop codons. Our findings
      highlight the importance of studying mutations at DNA and RNA levels in order to
      clarify the effect of the suspected mutation and to provide adequate counseling
      for breast/ovarian cancer families.

PMID- 18712472
TI  - Complementary and alternative therapies among very long-term breast cancer
      survivors.
AB  - Breast cancer patients may have different complementary and alternative medicine
      (CAM) usage rates and may turn to CAM for different reasons than healthy adults.
      CAM has mostly been studied in recently diagnosed women; no studies have included
      survivors 10 years post-diagnosis. We examined very long-term breast cancer
      survivors to determine whether CAM users had dissimilar patterns of association
      with survivorship factors. Interviews of 374 breast cancer case patients from a
      population-based case-control breast cancer study of young women from Los Angeles
      County, California, during the 1980s occurred at follow-up; 371 patients with
      complete information were included. CAM represented 28 herbal remedies. Quality
      of-life originated from the Medical Outcomes Study Short Form 36 questionnaire
      (SF-36). Higher rates of CAM (59%) usage occurred compared to nationwide
      estimates. CAM users resembled non-users on follow-up age, exercise, original
      disease, treatment, smoking, body-mass index, alcohol, and fear of recurrence.
      CAM users had a higher prevalence of medical co-morbidities (P = 0.0005), and
      scored significantly lower on the SF-36 emotional well-being subscale than non
      CAM users (P = 0.01). CAM users and non-users did not differ on the SF-36
      physical sub-scale. Very long-term breast cancer survivors who use CAM may have
      poorer emotional functioning and more medical problems than non-users.

PMID- 18712474
TI  - Syntheses of dopa glycosides using glucosidases.
AB  - Syntheses of L: -dopa 1a glucoside 10a,b and DL: -dopa 1b glycosides 10-18 with
      D: -glucose 2, D: -galactose 3, D: -mannose 4, D: -fructose 5, D: -arabinose 6,
      lactose 7, D: -sorbitol 8 and D: -mannitol 9 were carried out using
      amyloglucosidase from Rhizopus mold, beta-glucosidase isolated from sweet almond
      and immobilized beta-glucosidase. Invariably, L: -dopa and DL: -dopa gave low to
      good yields of glycosides 10-18 at 12-49% range and only mono glycosylated
      products were detected through glycosylation/arylation at the third or fourth OH
      positions of L: -dopa 1a and DL: -dopa 1b. Amyloglucosidase showed selectivity
      with D: -mannose 4 to give 4-O-C1beta and D: -sorbitol 8 to give 4-O-C6-O
      arylated product. beta-Glucosidase exhibited selectivity with D: -mannose 4 to
      give 4-O-C1beta and lactose 7 to give 4-O-C1beta product. Immobilized beta
      glucosidase did not show any selectivity. Antioxidant and angiotensin converting
      enzyme inhibition (ACE) activities of the glycosides were evaluated glycosides,
      out of which L: -3-hydroxy-4-O-(beta-D: -galactopyranosyl-(1'-->4)beta-D: 
      glucopyranosyl) phenylalanine 16 at 0.9 +/- 0.05 mM and DL: -3-hydroxy-4-O-(beta
      D: -glucopyranosyl) phenylalanine 11b,c at 0.98 +/- 0.05 mM showed the best
      IC(50) values for antioxidant activity and DL: -3-hydroxy-4-O-(6-D: 
      sorbitol)phenylalanine 17 at 0.56 +/- 0.03 mM, L: -dopa-D: -glucoside 10a,b at
      1.1 +/- 0.06 mM and DL: -3-hydroxy-4-O-(D: -glucopyranosyl)phenylalanine 11a-d at
      1.2 +/- 0.06 mM exhibited the best IC(50) values for ACE inhibition.

PMID- 18712475
TI  - Biology of TNFalpha and IL-10, and their imbalance in heart failure.
AB  - Our understanding of the multiple in vivo functions of the proinflammatory
      cytokine, tumor necrosis factor (TNFalpha), is advancing at a rapid pace. In
      addition to its antitumor effects, overproduction of TNFalpha provokes tissue
      injury and organ failure. TNFalpha has also been shown to be cardiodepressant and
      responsible for various cardiovascular complications. It appears that still much
      needs to be learned for a full comprehension of the role of TNFalpha in heart
      biology. Another cytokine, interleukin-10 (IL-10), has been shown to have anti
      inflammatory properties. It is suggested to counterbalance many adverse effects
      of TNFalpha. IL-10 suppresses the production of TNFalpha and many other
      proinflammatory cytokines. TNFalpha-induced oxidative stress is also known to be
      mitigated by IL-10. Moreover, improvement in cardiac function after treatment
      with various drugs is also shown to be associated with an increase in IL-10
      content. Based on the data reviewed in here, it is suggested that an optimal
      balance between IL-10 and TNFalpha may be a new therapeutic strategy for a
      healthier heart.

PMID- 18712477
TI  - Weighted analyses for cohort sampling designs.
AB  - Weighted analysis methods are considered for cohort sampling designs that allow
      subsampling of both cases and non-cases, but with cases generally sampled more
      intensively. The methods fit into the general framework for the analysis of
      survey sampling designs considered by Lin (Biometrika 87:37-47, 2000). Details
      are given for applying the general methodology in this setting. In addition to
      considering proportional hazards regression, methods for evaluating the
      representativeness of the sample and for estimating event-free probabilities are
      given. In a small simulation study, the one-sample cumulative hazard estimator
      and its variance estimator were found to be nearly unbiased, but the true
      coverage probabilities of confidence intervals computed from these sometimes
      deviated significantly from the nominal levels. Methods for cross-validation and
      for bootstrap resampling, which take into account the dependencies in the sample,
      are also considered.

PMID- 18712476
TI  - Characterization of phenytoin, carbamazepine, vinpocetine and clorgyline
      simultaneous effects on sodium channels and catecholamine metabolism in rat
      striatal nerve endings.
AB  - The effects of two classic antiepileptic drugs (carbamazepine and phenytoin), a
      potential antiepileptic (vinpocetine) and a monoamine-oxidase inhibitor
      (clorgyline) on the simultaneous changes (detected by HPLC) on Glu, Asp, dopamine
      and DOPAC inside and outside striatal isolated nerve endings were investigated.
      Under resting conditions phenytoin, carbamazepine and clorgyline increased
      dopamine release. Phenytoin and clorgyline increased internal dopamine and
      decreased DOPAC formation. Carbamazepine decreased internal dopamine and
      practically did not change DOPAC formation. Glu and Asp release was unchanged.
      Neurotransmitter release induced by the Na+ channel opener veratridine was
      reduced by all the antiepileptic drugs tested, except phenytoin which, like
      clorgyline, facilitated veratridine-induced dopamine release. We conclude that
      besides the antagonism exerted by carbamazepine, phenytoin and vinpocetine on
      excitatory neurotransmitters release triggered by Na+ channel activation, that
      might importantly contribute to their anticonvulsant action, they exert different
      actions on striatal dopamine distribution, that might explain their different
      side effect profiles.

PMID- 18712478
TI  - Autonomic dysfunctions in patients with inflammatory bowel disease in clinical
      remission.
AB  - INTRODUCTION AND OBJECTIVE: The autonomic nervous system, especially the
      parasympathetic system, has been reported to modulate the immune response in
      chronic inflammatory disorders. Autonomic dysfunctions have been reported earlier
      in patients with inflammatory bowel disease; however, the results have been
      conflicting. We therefore evaluated autonomic functions in patients with
      inflammatory bowel disease (IBD) in clinical remission. PATIENTS AND METHODS:
      Heart rate variability, a marker of autonomic functions, which included time
      domain, frequency-domain, and nonlinear indices (Poincare plot) was assessed
      using Nevrokard, version 6.4.0 Slovenia, in 118 patients with IBD (ulcerative
      colitis [UC] 62, and Crohn's disease [CD] 56) and 58 healthy controls. RESULTS:
      There was no difference in mean of R-R intervals in patients with UC, CD, and
      healthy controls. Frequency domain indices (absolute values of total power, high
      frequency power, and low-frequency power) were lower in patients with UC and CD
      vs. healthy controls. High-frequency (HFnu) (expressed in normalized units) was
      significantly lower in UC compared to healthy controls. There was no significant
      difference in the low-frequency (LFnu) and LF/HF ratio in UC, CD, and healthy
      controls. Amongst the Poincare plot indices, while standard deviation of the
      instantaneous R-R interval variability (SD1nu) was lower in UC and CD vs. healthy
      controls, there was no significant difference in the long-term R-R interval
      variability (SD2nu). CONCLUSIONS: Patients with inflammatory bowel disease have
      lower autonomic functions. Patients with UC have significantly lower
      parasympathetic function in comparison to those with CD and healthy controls.
      These autonomic dysfunctions in patients with IBD may have a bearing on the
      pathogenesis of IBD.

PMID- 18712479
TI  - Randomized study comparing two regimens of oral sodium phosphates solution versus
      low-dose polyethylene glycol and bisacodyl.
AB  - PURPOSE: Low-volume bowel preparation regimens for colonoscopy are reported to
      improve patient acceptance and compliance. We sought to compare the bowel
      cleansing efficacy, tolerability, and acceptability of three low-volume regimens:
      an oral sodium phosphates solution 45/45 ml (NaP-45/45), a reduced-dose oral
      sodium phosphates solution 45/30 ml (NaP-45/30), and polyethylene glycol plus
      bisacodyl (PEG-2L). RESULTS: A total of 121 patients were evaluated (mean age
      55.2 +/- 8.9 years). Bowel cleansings rated as excellent and good were
      significantly different among the groups: NaP-45/45 = 98%, NaP-45/30 = 88%, and
      PEG-2L = 76% (P < 0.04). Side effects were not significantly different except for
      greater thirst in the NaP-45/45 group (P = 0.001) and increased vomiting in
      females using PEG-2L (two-tailed interaction, P < 0.10). Willingness to retake
      the preparation was higher among the sodium phosphates regimens (88, 95, and 73%,
      respectively; P = 0.019). CONCLUSIONS: Better cleansing and willingness to retake
      the regimen was achieved with the oral sodium phosphates solutions than with
      polyethylene glycol plus bisacodyl.

PMID- 18712480
TI  - R0 liver resections for primary malignant liver tumors in the noncirrhotic liver:
      a diagnosis-related analysis.
AB  - BACKGROUND: Primary liver cancer constitutes an increasingly malignancy in the
      Western world and one of the leading causes of cancer-related deaths worldwide.
      The purpose of this study was to evaluate and compare long-term outcomes after R0
      resections in noncirrhotic livers for hepatocellular carcinoma (HCC) and
      intrahepatic cholangiocarcinoma (ICC). METHODS: Between April 1998 and May 2006 a
      total of 102 patients with either ICC (n = 41, group 1) or HCC (n = 61, group 2)
      in the absence of cirrhosis underwent curative liver resection in our department.
      Demographic characteristics, operative details, perioperative complications,
      pathologic findings, tumor recurrence and survival were analyzed. RESULTS: Gender
      (P = 0.007), extent of liver resection (P = 0.036), additional surgical
      procedures (P < 0.001) and operative morbidity (P = 0.018) differed among the two
      groups. Following resection, after a median follow-up of 28 months, the
      calculated 5-year survival was 44% and 40% for ICC and HCC, respectively (P =
      0.38). The corresponding recurrence-free survival was 25% for both ICC and HCC (P
      = 0.66). UICC stage was found to predict overall and recurrence-free survival in
      both types of tumors. Multifocality in the case of ICC, and tumor differentiation
      and vascular invasion in the case of HCC, were predictive factors for overall and
      recurrence-free survival, respectively. In multivariable analyses, vascular
      invasion for HCC was predictive for overall and recurrence-free survival, whereas
      in the case of ICC significant differences were detected in the recurrence
      analysis for multifocality and UICC stage. CONCLUSIONS: R0 resections for both
      ICC and HCC result to similar long-term outcomes, which are characterized by good
      overall and acceptable recurrence-free survival rates.

PMID- 18712481
TI  - Reports of substance abuse prevention programming available in schools.
AB  - Evaluations of school-based substance abuse prevention programs with schools or
      school districts randomly assigned to either the treatment or control condition
      have demonstrated effective strategies over the past 30 years. Although control
      schools were never considered "pure" (i.e., no other interventions were being
      offered), school-based programming in the 1980s did not include evidence-based
      interventions. Since the late 1990s, funding agencies have required schools
      either to select programming from approved lists of prevention strategies or to
      demonstrate the efficacy of the strategies that would be used. This has increased
      the number of schools delivering evidence-based programs to their students. As a
      result, "treatment as usual" is more challenging to researchers. This paper
      describes exposure to prevention programming as reported by 204 school
      administrators from 83 districts and their 19,200 students who are participating
      in the Adolescent Substance Abuse Prevention Study, a national randomized
      evaluation trial of the program, Take Charge of Your Life. In order to determine
      the extent of student exposure to prevention programming in both the control and
      treatment schools, data were collected in each of the 5 years of the study from
      two sources: principals and prevention coordinators and from students. The data
      provided by the principals and prevention coordinators indicate that the vast
      majority of schools assigned to the control condition offered students drug
      prevention programming. This finding has implications for the evaluation of Take
      Charge of Your Life but also for other evaluation studies. The students were
      asked questions regarding participation in drug education posed on annual
      surveys. When their responses were compared to the reports from their school
      principals and prevention coordinators, it was found that the students
      underreported exposure to drug education. A follow-up qualitative study of a
      sample of students suggests the need for rewording of the questions for students
      in future studies. The implications of our findings for evaluation studies are
      discussed.

PMID- 18712482
TI  - Law in practice: obstacles to a smokefree workplace policy in bars serving Asian
      patrons.
AB  - The California smokefree workplace ordinance (AB13) has been well-received, even
      in bars where deeply established traditions of smoking may exist. However, a
      closer investigation of bars where indoor smoking persists revealed that bar
      workers in some ethnic minority communities continue to be exposed to secondhand
      smoke in their workplaces. To identify sociocultural factors that may impede the
      adoption of AB13, the researchers conducted 150 observations and 29 patron and
      staff interviews in 50 California bars serving Asian patrons in Los Angeles and
      San Francisco counties. Observers witnessed indoor smoking in 82% of the bars.
      Interviews revealed that social relationships, social interactions, and a
      tendency to avoid confrontation complicated the positive reception of AB13 within
      these bars. Accounting for sociocultural factors provides a nuanced understanding
      of the challenges involved in implementing tobacco control policy in such diverse
      settings and may allow for culturally appropriate tobacco policy development and
      implementation in other jurisdictions.

PMID- 18712483
TI  - Pain management for hepatobiliary cancer.
AB  - OPINION STATEMENT: Although many options exist to address hepatobiliary cancer
      induced pain, it remains undertreated and has an adverse impact on quality of
      life. Fortunately, if addressed appropriately, the majority of patients can be
      treated successfully. This pain may be nociceptive, neuropathic, or a combination
      of the two. A multimodality approach including oral and intravenous opioid and
      non-opioid medications, and interventional approaches including celiac plexus
      blocks and implantation of drug delivery systems for intrathecal delivery of
      opioids can be considered and utilized as appropriate. We review the
      pathophysiology of pain, the approach to correctly diagnosing the different types
      of pain, the appropriate treatment recommendations, and how to avoid and address
      the common side effects resulting from these treatments.

PMID- 18712484
TI  - The analysis of randomised controlled trial data with more than one follow-up
      measurement. A comparison between different approaches.
AB  - When more than one follow-up measurement is analysed in a randomized controlled
      trial, there is no consensus how to analyse the overall intervention effect in a
      proper way. Mostly, longitudinal analysis of covariance is used, because with
      this method a correction is made for possible regression to the mean. However, in
      this paper it is shown that this method (mostly) leads to an overestimation of
      the intervention effect. A possible solution is the use of autoregression,
      although this does not seem to be the best solution, because it leads to an
      overcorrection. Due to these flaws, in this paper a new approach is introduced in
      which a correction for the baseline value is made for the first follow-up, but no
      correction is made for the remaining follow-up measurements.

PMID- 18712486
TI  - Effect of "All - trans" retinoic acid in canine osteosarcoma chemotherapy.

PMID- 18712485
TI  - Indoor air pollution levels in public buildings in Thailand and exposure
      assessment.
AB  - Levels of pollutants including PM2.5 and PM2.5 composition (black carbon and
      water soluble ions), SO(2), NO(2), CO, CO(2), and BTEX (benzene, toluene,
      ethylbenzene, xylene) were monitored for indoor and outdoor air at a university
      campus and a shopping center, both located in the Northern suburb of Bangkok.
      Sampling was done during December 2005-February 2006 on both weekdays and
      weekends. At the university, indoor monitoring was done in two different air
      conditioned classrooms which shows the I/O ratios for all pollutants to be below
      0.5-0.8 during the weekends. However, on weekdays the ratios for CO(2) and most
      detected BTEX were above 1.0. The concept of classroom occupancy was defined
      using a function of the student number in a lecture hour and the number of
      lecture hours per day. Classroom 2, which had a higher occupancy than classroom
      1, was characterized by higher concentrations of most pollutants. PM2.5 was an
      exception and was higher in classroom 1 (37 microg/m(3), weekdays) as compared to
      classroom 2 (26 microg/m(3), weekdays) which was likely linked to the dust
      resuspension from the carpeted floor in the former. Monitoring was also done in
      the shopping mall at three different sites. Indoor pollutants levels and the I/O
      ratios at the shopping mall were higher than at the university. Levels of all
      pollutants measured at the car park, except for toluene and CO(2), were the
      highest. I/O ratios of the pollutants at the mall were above 1.0, which indicates
      the relatively higher influence of the indoor sources. However, the black carbon
      content in PM2.5 outdoor is higher than indoor, which suggest the important
      contribution from outdoor combustion sources such as the traffic. Major sources
      of outdoor air pollution in the areas were briefly discussed. Exposure modeling
      was applied using the time activity and measured pollutant concentrations to
      assess the exposure of different groups of people in the study areas. High
      exposure to PM2.5, especially for the people working in the mall, should be of
      health effect concern.

PMID- 18712487
TI  - Phytoestrogen treatment induces testis alterations in dogs. Potential use in
      population control.
AB  - Dog overpopulation is considered a human health risk; they are the terrestrial
      vector of rabies and reservoirs for other human diseases. Surgical neutering and
      intratesticular injections have been used in male dogs. Physiological and
      morphological alterations in reproductive organs can be induced by
      phytoestrogens. Our goal was to evaluate the effect of oral coumestrol on dog
      ejaculates and testis histology. Two groups of 5 healthy adult dogs were used.
      One coumestrolcontaining biscuit was given once a week for a 4 week period to the
      experimental group. Ejaculates were obtained and evaluated. After treatment,
      testis were obtained and processed for histology. Compared to controls, treated
      dogs have reduced tubules (462 +/- 1.4 vs 336 +/- 2 micron(2)), spermatogenic
      epithelium (49.1 +/- 0.01 vs 13.3 +/- 0.01 micron(2)), and lumen opening (891 +/-
      1.4 vs 530 +/- 26.9 micron). Ejaculates from treated animals have increased
      numbers of abnormal spermatozoa and reduced sperm concentration.

PMID- 18712489
TI  - Analysis and quantification of self-medication patterns of customers in community
      pharmacies in southern Chile.
AB  - BACKGROUND: Self-medication refers to using drugs which have not been prescribed,
      recommended or controlled by a licensed health care specialist. Marketing, in
      Chile only admitted for over-the-counter medications, influences the practice of
      self-medication and extends it to prescription drugs. Thus, a complex self
      medication process is started, due to reuse of a previous prescription, using
      drugs purchased directly at the pharmacy or drugs coming from family first-aid
      kits. The purpose of this study is to determine the frequency of self-medication,
      the type of medications involved, the dosages used, and the reasons for this
      practice. METHODS: An observation-based cross-sectional study was carried out at
      three pharmacies belonging to a pharmacy chain in the city of Valdivia (southern
      Chile). In addition, a previously validated form was used. Customers who
      requested over-the-counter medications were surveyed to identify the patterns
      that foster the self-medication practice. RESULTS: Of 909 surveyed customers, 75%
      self-medicate. Of these, 31% stated that they commonly self-medicate due to
      suffering from light symptoms, such as headaches (19%), the common cold (8.8%),
      sore muscles (6.7%), and bone pains (5.3%). The group of medications most
      requested in this study was nonsteroidal anti-inflammatory drugs (NSAIDs) (33%),
      with diclofenac sodium being the most used (14%). Influence from other people did
      not exceed 20% and reusing prior prescriptions reached 46%. There were
      significant differences when assessing consumer knowledge, reading of information
      leaflets, and opinions about self-medication at each surveyed pharmacy (P <
      0.001). CONCLUSION: Most consumers at the surveyed pharmacies use medications
      without proper knowledge of their benefits, treatment method, and duration. Drug
      dispensing at community pharmacies should include active pharmacist involvement
      to divulge the sensible use of drugs.

PMID- 18712490
TI  - The inhibitory effects of acidification and augmented oxygen pressure on water
      oxidation.
AB  - Cyanobacteria, algae, and plants produce dioxygen from water. Driven and clocked
      by light quanta, the catalytic Mn(4)Ca Tyrosine centre accumulates four oxidizing
      equivalents before it abstracts four electrons from water and liberates dioxygen
      and protons. Intermediates of this reaction cascade are short-lived (<100 micros)
      and difficult to detect. By application of high oxygen pressure to cyanobacterial
      PSII-core-complexes, we have previously suppressed the transition from the
      highest oxidation state of the centre to the lowest by stabilizing a (peroxy)
      intermediate. Here, we investigated the inhibitory interplay of acidification and
      augmented oxygen pressure. Starting from pH 6.5, acidification increasingly
      inhibited the reduction of the highest oxidized state and resulted in a lower
      oxygen partial pressure for half inhibition. Oxygen and proton interfere with
      different steps of the reaction cascade.

PMID- 18712491
TI  - Benzyl alcohol inhibits N-methyl-D: -aspartate receptor-mediated neurotoxicity
      and calcium accumulation in cultured rat cortical neurons.
AB  - The purpose of this study is to examine whether benzyl alcohol affects N-methyl-D
      aspartate (NMDA) receptor in cortical cells. Benzyl alcohol (0.5-2 mM) inhibited
      NMDA-induced cytotoxicity. The protective effect of benzyl alcohol on NMDA
      induced toxicity disappeared by washing cells with buffer to remove benzyl
      alcohol. Benzyl alcohol reduced NMDA receptor-mediated calcium accumulation,
      indicating that benzyl alcohol inhibits NMDA receptor activity.

PMID- 18712492
TI  - CGcgh: a tool for molecular karyotyping using DNA microarray-based comparative
      genomic hybridization (array-CGH).
AB  - Microarray-based comparative genomic hybridization (array-CGH) is a technique by
      which variations in copy numbers between two genomes can be analyzed using DNA
      microarrays. Array CGH has been used to survey chromosomal amplifications and
      deletions in fetal aneuploidies or cancer tissues. Herein we report a user
      friendly, MATLAB-based, array CGH analyzing program, Chang Gung comparative
      genomic hybridization (CGcgh), as a standalone PC version. The analyzed
      chromosomal data are displayed in a graphic interface, and CGcgh allows users to
      launch a corresponding G-banding ideogram. The abnormal DNA copy numbers (gains
      and losses) can be identified automatically using a user defined window size
      (default value is 50 probes) and sequential student t-tests with sliding windows
      along with chromosomes. CGcgh has been tested in multiple karyotype-confirmed
      human samples, including five published cases and trisomies 13, 18, 21 and X from
      our laboratories, and 18 cases of which microarray data are available publicly.
      CGcgh can be used to detect the copy number changes in small genomic regions,
      which are commonly encountered by clinical geneticists. CGcgh works well for the
      data from cDNA microarray, spotted oligonucleotide microarrays, and Affymetrix
      Human Mapping Arrays (10K, 100K, 500K Array Sets). The program can be freely
      downloaded from http://www.mcu.edu.tw/department/biotec/en%5Fpage/CGcgh/ .

PMID- 18712495
TI  - Amino acids as precursors of trihalomethane and haloacetic acid formation during
      chlorination.
AB  - Twenty amino acids were chlorinated and examined for the formation of
      trihalomethane (THM) and haloacetic acid (HAA). The amino acids exhibited a high
      Cl(2) demand (3.4-10 mg Cl(2) mg(-1) C) but low THM formation (<4.19 microg mg(
      1) C) except for tryptophan and tyrosine (45.8 - 147 microg mg(-1) C). Large
      variation in HAA yield occurred among the amino acids (from not detectable to 106
      microg mg(-1) C). One group of amino acids, possessing chain structures,
      exhibited a slow increase in HAA formation (<6.2 micromol mol(-1) amino acid or
      <11.3 microg mg(-1) C) as the chlorine demand increased (3.4-8.9 mol Cl(2) mol(
      1) amino acids). The other group of amino acids, containing ring structures
      (including tryptophan, tyrosine, histidine, phenylalanine, and proline) and two
      amino acids with chain structures (aspartic acid and asparagine), showed a fast
      increase in HAA formation (16-96 micromol mol(-1) amino acid or 27-106 microg mg(
      1) C) with the increase in chlorine demand (5.2-15.9 mol Cl(2) mol(-1) amino
      acid). The ratios of TCAA to DCAA (mol/mol), derived from the amino acids, ranged
      between 0.01 and 1.10.

PMID- 18712494
TI  - Mutual stimulation of beta-amyloid fibrillogenesis by clioquinol and divalent
      metals.
AB  - As reported by some authors, clioquinol (CQ), a 8-hydroxyquinoline derivative,
      has produced very encouraging results in the treatment of Alzheimer's disease
      (AD). Its biological effects are most likely ascribed to complexation of specific
      metal ions, such as copper (II) and zinc (II), critically associated with beta
      amyloid (A beta) aggregation/fibrillogenesis and degeneration processes in the
      brain. The present study was aimed at assessing the in vitro effects of CQ on the
      aggregation/fibrillogenesis properties of human A beta either alone or complexed
      with Cu(2+) and Zn(2+). Surprisingly, our data indicated that CQ promoted rather
      than inhibited the formation of A beta fibrillar aggregates when added metal ions
      were present. To understand whether the latter effects were related to the
      peptide amino acid sequence, we also investigated the aggregational profile of
      rat A beta, which differs from the human homologous for three amino acidic
      substitutions. Such a sequence alteration drastically reduced the tendency of the
      peptide to undergo spontaneous aggregation/fibrillization. In the presence of CQ
      and metals, however, also rat A beta showed a strong propensity to generate
      fibrillar aggregates. In agreement with the pro-aggregation effects observed in
      solution, studies with neuroblastoma cells demonstrated an impairment of cell
      functioning only in the presence of CQ + A beta-metals. Based on the present
      findings, the literature data on the potential effectiveness of CQ-based
      chelation therapy in AD should be re-interpreted.

PMID- 18712496
TI  - Toxic element concentrations in the Razorbill Alca torda (Charadriiformes,
      Alcidae) in Portugal.
AB  - The present study provides the first data on inorganic element levels (As, Cd,
      Co, Cr, Cu, Hg, Mn, Pb, Se, and Zn) in juvenile, immature, and adult razorbills
      (Alca torda) collected along the central coast of Portugal. Element
      concentrations were assessed by ICP-MS in kidney, liver, muscle, and feathers of
      28 razorbills, including 4 juveniles, 17 subadults, and 7 adults. The effect of
      age and tissue on element accumulation was also assessed. The detected levels in
      razorbills may indicate a possible contamination risk by Hg and Cr. With respect
      to bird tissues, higher accumulation of Se and Cd was detected in kidney, Zn and
      Pb in feathers, and As and Mn in liver. Age was found to affect the accumulation
      of Cd, Cr, Cu, Hg, and Mn, juveniles presenting higher levels of Cu and Mn than
      older individuals. In razorbill kidney, Zn-Hg constituted the most significant
      relationship among metal concentrations. Liver presented the highest number of
      significant relationships (mostly involving Zn and Co). With regard to feathers,
      the most significant relationships involved Se, Zn, Cr and Cu concentrations.
      Positive linear relationships were detected among kidney, liver, and muscle, with
      emphasis on relationships involving Se and Hg, which may be indicative of similar
      accumulation/regulation mechanisms in those organs. Element concentrations are
      discussed in view of possible detoxification mechanisms in seabirds.

PMID- 18712497
TI  - Respiratory irritants in Australian bushfire smoke: air toxics sampling in a
      smoke chamber and during prescribed burns.
AB  - Bushfire smoke contains an array of organic and inorganic compounds, including
      respirable and inspirable particles, aldehydes, and carbon monoxide. These
      compounds have been found to be a health hazard for firefighters in the United
      States. Despite the high frequency of bushfires in Australia, analyses of
      bushfire smoke components are scarce. As part of an occupational health study
      investigating the respiratory health effects of bushfire smoke in firefighters,
      air toxics sampling was undertaken in a smoke chamber and during prescribed
      burns. Levels of formaldehyde and acrolein were demonstrated at respectively 60%
      and 80% of the Short Term Exposure Limit in the smoke chamber. Carbon monoxide
      levels exceeded the peak limit of 400 ppm significantly. Although concentrations
      were lower during the prescribed burns, the study shows that Australian bushfire
      smoke contains air toxics of concern and provides justification for further
      research into the levels of air toxics measured at bushfires and the associated
      health impacts.

PMID- 18712498
TI  - Diseases of the Chilean flounder Paralichthys adspersus (Steindachner, 1867) as
      biomarkers of marine coastal pollution near the Itata River (Chile). Part I: in
      situ macroscopic lesions.
AB  - This study evaluated the health of the Chilean flounder Paralichthys adspersus
      inhabiting the marine coastal area influenced by the Itata River. Flounder were
      also sampled at two reference sites during the course of 1 year. The pathological
      examination was done following the ICES protocol: external and internal lesions,
      condition factor, hepatosomatic and spleen indexes, and number of erythrocytes,
      lymphocytes, and thrombocytes. The prevalence of fish with lesions differed
      significantly among sites. The flounder sampled in the Itata area were the most
      affected. The evaluation of the macroscopic lesions observed on the flounder
      caught in the Itata area revealed (1) seven different types of macroscopic
      lesions, (2) a high prevalence of epidermal irritation lesions, and (3) a normal
      K factor, hepatosomatic index, and blood cell count. Significant differences were
      found in epidermal irritation lesions between stages and sites and between sexes
      and sites. Juveniles and adults as well as males and females were affected. A
      seasonal analysis of the macroscopic lesions on the flounder caught in the Itata
      area showed significant differences for only the epidermal irritation lesions
      between the sampled seasons of the year; the flounder caught in winter 2006 had
      the highest prevalence (77%) of such lesions. These results are discussed in
      relation to the hydrographic conditions, the contents of inorganic, nutrient and
      other organic compounds in the water column, and the contents of organic
      compounds and metals in the sediments of the subtidal environment in the Itata
      area.

PMID- 18712499
TI  - Mercury and other metals in feathers of common eider (Somateria mollissima) and
      tufted puffin (Fratercula cirrhata) from the Aleutian chain of Alaska.
AB  - We analyzed arsenic, cadmium, chromium, lead, manganese, mercury, and selenium in
      the feathers of common eiders (Somateria mollissima) and tufted puffins
      (Fratercula cirrhata) from Amchitka and Kiska islands (Aleutians). Between
      species, puffins had 10 times higher chromium (arithmetic mean = 1820 ppb), 7.5
      times higher selenium (mean = 6600 ppb), and 3 times higher mercury (mean = 2540
      ppb) than eiders. Eiders had significantly higher levels of manganese than
      puffins. Puffins are higher on the food chain than eiders, which is reflected in
      their generally higher levels of metals in their feathers. Interisland
      differences were generally small, and there were few significant differences as a
      function of the three nuclear test locations on Amchitka. The only sex-related
      difference was that female puffins had higher mercury than males (arithmetic mean
      of 3060 ppb vs. 2270 ppb). Mean levels of metals in the feathers of puffins and
      eiders from the Aleutians were low compared with comparable studies elsewhere,
      and the relatively low levels of metals do not indicate the potential for adverse
      behavioral or reproductive effects in the birds themselves, nor pose concern for
      other consumers, including subsistence hunters.

PMID- 18712500
TI  - Demographic responses to multigeneration cadmium exposure in two strains of the
      freshwater gastropod, Biomphalaria glabrata.
AB  - A life table response experiment (LTRE) was used to quantify the population-level
      effects of continuous, multigeneration cadmium exposure on two strains of the
      freshwater gastropod, Biomphalaria glabrata: the parasite-resistant BS90 and
      parasite-susceptible NMRI strains. Snails were exposed to waterborne cadmium for
      three consecutive generations. Survival, growth, and reproduction were measured
      empirically and incorporated into a stage-based, deterministic population model.
      Cadmium significantly affected hatching success, time to maturity, and juvenile
      and adult survival in both strains. There were significant effects of generation
      on fecundity, hatching success, time to maturity and juvenile survival in NMRI,
      and time to maturity and adult survival in BS90. Cadmium significantly affected
      the population growth rate, lambda, in BS90. Cadmium, generation, and the cadmium
      x generation interaction had significant effects on lambda in NMRI. At the high
      cadmium exposure, lambda for NMRI showed a decrease from generation 1 to
      generation 2, followed by an increase from generation 2 to generation 3. The
      lambda value in high-cadmium BS90 steadily decreased over the three generations,
      while NMRI at this same concentration was similar to the controls. The results
      indicate that strain-specific differences in response to multigeneration cadmium
      exposure are evident in B. glabrata. Moreover, effects seen in the first
      generation are not necessarily indicative of effects in subsequent generations.
      Changes in lambda over the course of the three-generation exposure suggest that
      acclimation and/or adaptation to cadmium may have occurred, particularly in NMRI
      at the high cadmium exposure level.

PMID- 18712501
TI  - Effects of activated Bt transgene products (Cry1Ab, Cry3Bb) on immature stages of
      the ladybird Adalia bipunctata in laboratory ecotoxicity testing.
AB  - Insect-active Bacillus thuringiensis (Bt) proteins are expressed by several
      transgenic crop plants to control certain pests, but nontarget organisms such as
      ladybirds also can be exposed to these proteins in the field. We developed an
      improved ecotoxicity testing protocol and conducted feeding trials in a
      laboratory setting to test for possible adverse effects of different
      concentrations of microbially produced trypsin-activated Cry1Ab and Cry3Bb toxins
      on the coccinellid Adalia bipunctata. Larval/pupal mortality, development time,
      and overall body mass accumulation were recorded. Even at the lowest
      concentration (5 microg/ml), A. bipunctata larvae fed with the lepidopteran
      active Cry1Ab toxin exhibited significantly higher mortality than the control
      group. In experiments with the coleopteran-active Cry3Bb, only a concentration of
      25 microg/ml resulted in a marginally significantly higher mortality compared to
      the control. Both experiments revealed a slight decline in mortality at the
      highest concentration of 50 microg/ml, though this was statistically significant
      only in the Cry1Ab treatment. No differences were detected for development time
      and body mass of newly emerged adults. Dilutions of the expression vector pBD10-
      used as a control to exclude effects of the toxin production method--at
      concentrations between 10 and 100 microg/ml revealed no significant effects on
      either of the studied parameters. This suggests that the increased mortality of
      larvae in the toxin feeding trials was caused directly by the activated Bt toxins
      and raises questions regarding their commonly postulated specificity and their
      mode of action in A. bipunctata. Implications of the reported results for
      ladybird populations and their biological pest control functions in transgenic
      crop ecosystems are discussed.

PMID- 18712502
TI  - A pilot trial of the anti-angiogenic copper lowering agent tetrathiomolybdate in
      combination with irinotecan, 5-flurouracil, and leucovorin for metastatic
      colorectal cancer.
AB  - Tetrathiomolybdate (TM) is an oral copper chelator under development as an anti
      angiogenic agent. We evaluated TM in combination with irinotecan, 5-fluorouracil,
      and leucovorin (IFL). Serum vascular endothelial growth factor (VEGF), basic
      fibroblast growth factor, interleukin 6 (IL-6), and IL-8 were measured to
      evaluate the anti-angiogenic effect. Twenty-four patients with metastatic
      colorectal cancer were treated. The combination with IFL was well tolerated and
      dose intensity of IFL was maintained during combination therapy with TM. By
      intention to treat analysis, the overall response rate (RR) was 25% (95% CI 9.8
      46.7) and the median time to progression (TTP) was 5.6 months (95% CI 2.7-7.7).
      VEGF levels were correlated with TTP, as were changes in VEGF, IL-8, and IL-6. TM
      can be safely added to IFL without compromising dose intensity or diminishing the
      expected RR. Changes in serum VEGF, IL-8, and IL-6 after treatment may directly
      reflect changes in CRC tissue angiogenesis.

PMID- 18712503
TI  - Application of population pharmacokinetic modeling in early clinical development
      of the anticancer agent E7820.
AB  - The aim of this study was to assess the population pharmacokinetics (PopPK) of
      the novel oral anti-cancer agent E7820. Both a non-linear mixed effects modeling
      analysis and a non-compartmental analysis (NCA) were performed and results were
      compared. Data were obtained from a phase I dose escalation study in patients
      with malignant solid tumors or lymphomas. E7820 was administered daily for 28
      days, followed by a washout period of 7 days prior to the start of subsequent
      cycles. A one compartment model with linear elimination from the central
      compartment was shown to give adequate fit, while absorption was described using
      a turnover model. Final population parameter estimates of basic PK parameters
      obtained with the PopPK method were (RSE): clearance, 6.24 L/h (7.1%), volume of
      distribution, 66.0 L (8.5%), mean transit time to the absorption compartment,
      0.638 h (6.5%). The intake of food prior to dose administration slowed absorption
      (2.8-fold, RSE 13%) and increased relative bioavailability of E7820 by 36% (RSE
      14%), although the effect on C (max) and AUC was not significant. Comparison with
      the NCA approach showed approximately equal PK parameter estimates and food
      effect measures, although specific advantages of PopPK included efficiency in use
      of data and more appropriate assessment of variability.

PMID- 18712504
TI  - An investigation of microbial adhesion to natural and synthetic polysaccharide
      based films and its relationship with the surface energy components.
AB  - In recent years, polysaccharide-based films have been developed for many
      applications. Some of these are in the pharmaceutical industry, where the
      adhesion of microorganisms to surfaces is a concern. After adhesion of a
      microorganism to a solid surface has taken place, the subsequent biofilm formed
      can act as a vehicle for spreading infections. The aim of this study is to
      compare the bacterial adhesion of E. coli and S. aureus from a contaminated solid
      model (Tryptone Soya Agar) to a range of polysaccharide-based films. These
      polysaccharide-based films consist of different natural starches (potato,
      cassava, wheat, pea and rice) and synthetic polymers hydroxyl-propyl cellulose
      (HPC) and carboxyl methyl cellulose (CMC)). The surface energy parameters of the
      films were calculated from the contact angle measurements by the sessile drop
      method. Apolar and polar liquids (water, formamide and hexadecane) and the
      Lifshitz-Van der Waals/acid-base (LW/AB) approach were used according to the
      method of Van Oss, Chaundhury and Good. The surface properties of the films were
      also correlated to the microbial adhesion. This indicated that, for both E. coli
      and S. aureus, the surface roughness did not affect the microbial adhesion. Only
      gamma(sAB) had any correlation with the microbial adhesion and gamma(sLW) was
      almost constant for all the various polysaccharide films tested. In addition, the
      electron-donor properties of the materials, exhibited via gamma(s+), were
      positively correlated with the adhesion of S. aureus but not with E. coli. This
      was in agreement with the results of the MATS (Microbial Adhesion To Solvents)
      test performed on the two bacteria. This revealed that only S. aureus presented
      an electron-acceptor characteristic.

PMID- 18712505
TI  - The use of dual beam ESEM FIB to reveal the internal ultrastructure of
      hydroxyapatite nanoparticle-sugar-glass composites.
AB  - Microparticles (MP) spray dried from hydroxyapatite (HA) nanoparticle (NP) sugar
      suspensions are currently under development as a prolonged release vaccine
      vehicle. Those with a significant sugar component cannot be sectioned by
      ultramicrotomy as resins are excluded by the sugar. Focused ion beam (FIB)
      milling is the only method to prepare thin sections that enables the inspection
      of the MPs ultrastructure by transmission electron microscopy (TEM). Several
      methods have been explored and we have found it is simplest to encapsulate MPs in
      silver dag, sandwiched between gold foils for FIB-milling to enable multiple MPs
      to be sectioned simultaneously. Spray dried MPs containing 80% sugar have an
      inter-nanoparticle separation that is comparable with NP size (approximately 50
      nm). MPs spray dried with 50% sugar or no sugar are more tightly packed. Nano
      porosity in the order of 10 nm exists between NPs. MPs spray dried in the absence
      of sugar and sectioned by ultramicrotomy or by FIB-milling have comparable
      nanoscale morphologies. Selected area electron diffraction (SAED) demonstrates
      that the HA remains (substantially) crystalline following FIB-milling.

PMID- 18712506
TI  - Evolution of Chilean colonizing populations of Drosophila subobscura: lethal
      genes and chromosomal arrangements.
AB  - Knowledge of the frequency, distribution, and fate of lethal genes in chromosomal
      inversions helps to illuminate the evolution of recently founded populations. We
      analyze the relationship between lethal genes and inversions in two colonizing
      populations of D. subobscura in Chile. In the ancestral Palearctic populations of
      this species, lethal genes seem distributed at random on chromosomes. But in
      colonizing American populations, some lethal genes are associated with specific
      chromosomal arrangements. Some of these associated lethals were detected only
      during the first stages of the colonization (O( 3+4+2 )), and never thereafter,
      whereas others have persisted (O( 3+4+7 ) and O(5)). However, most lethal genes
      in American populations have been observed only once: they have arisen by novel
      mutation and soon disappear. Finally, recombination between different inversions
      has been observed in America. However, the persistence of lethal genes associated
      with the heterotic inversions O( 3+4+7 ) and O(5) could indicate that
      recombination inside these inversions is rare.

PMID- 18712507
TI  - The use of microporous divinyl benzene copolymer for yeast cell immobilization
      and ethanol production in packed-bed reactor.
AB  - Microporous divinyl benzene copolymer (MDBP) was used for the first time as
      immobilization material for Saccharomyces cerevisiae ATCC 26602 cells in a bed
      reactor and ethanol production from glucose was studied as a model system. A very
      homogenous thick layer of yeast cells were seen from the scanning electron
      micrographs on the outer walls of biopolymer. The dried weight of the cells was
      found to be approximately 2 g per gram of cell supporting material. Hydrophobic
      nature of polymer is an important factor increasing cell adhesion on polymer
      pieces. The dynamic flow conditions through the biomaterial due to its
      microporous architecture prevented exopolysaccharide matrix formation around
      cells and continuous washing out of toxic metabolites and dead and degraded cells
      from the reactor provided less diffusional limitations and dynamic living
      environment to the cells. In order to see the ethanol production performance of
      immobilized yeast cells, a large initial concentration range of glucose between
      6.7 and 300 g/l was studied at 1 ml/min in continuous packed-bed reactor. The
      inhibition effect of glucose with increasing initial concentration was observed
      at above 150 g/l, a relatively high substrate concentration. The continuous fluid
      flow around the microenvironment of the attached cells and mass transferring
      ability of cell immobilized on MDBP can help in decreasing the inhibition effect
      of ethanol accumulation and high substrate concentration in the vicinity of the
      cells.

PMID- 18712508
TI  - The parkinsonism-hyperpyrexia syndrome.
AB  - The parkinsonism-hyperpyrexia syndrome (PHS) is a rare but potentially fatal
      complication seen in Parkinson's disease (PD) patients, most commonly following
      reduction or cessation of antiparkinson medications. Clinically it resembles
      neuroleptic malignant syndrome with rigidity, pyrexia, and reduced conscious
      level. There may be features of autonomic instability, and serum creatine kinase
      (CK) may be elevated. Complications of PHS include acute renal failure,
      aspiration pneumonia, deep venous thrombosis/pulmonary embolism, and disseminated
      intravascular coagulation (DIC). Management consists of dopaminergic drug
      replacement, supportive measures, and treatment of complications. The prognosis
      is improved with early recognition and management. Mortality of up to 4% has been
      reported, but an additional one-third of patients have permanent sequelae.
      Patients and physicians should be warned against sudden reduction in
      antiparkinson medications. PHS should always be considered in a patient with
      parkinsonism who presents with an acute deterioration in symptoms.

PMID- 18712509
TI  - Epidermal neural crest stem cells (EPI-NCSC) and pluripotency.
AB  - This article serves three purposes. We summarize current knowledge of the origin
      and characteristics of EPI-NCSC, review their application in a mouse model of
      spinal cord injury, and we present new data that highlight aspects of
      pluripotency of EPI-NCSC. EPI-NCSC are multipotent stem cells, which are derived
      from the embryonic neural crest and are located in the bulge of hair follicles.
      EPI-NCSC can undergo self-renewal and they are able to generate all major neural
      crest derivatives, including neurons, nerve supporting cells, smooth muscle
      cells, bone/cartilage cells and melanocytes. Despite their ectodermal origin,
      neural crest cells can also generate cell types that typically are derived from
      mesoderm. We were therefore interested in exploring aspects of EPI-NCSC
      pluripotency. We here show that EPI-NCSC can fuse with adult skeletal muscle
      fibers and that incorporated EPI-NCSC nuclei are functional. Furthermore, we show
      that adult skeletal muscle represents an environment conducive to long-term
      survival of neurogenic EPI-NCSC. Genes used to create induced pluripotent stem
      (iPS) cells are present in our EPI-NCSC longSAGE gene expression library. Here we
      have corroborated this notion by real-time PCR. Our results show similarities in
      the expression of Myc, Klf4, Sox2 and Lin28 genes between EPI-NCSC and embryonic
      stem cells (ESC). In contrast there were major differences in Nanog and Pou5f1
      (Oct-4) expression levels between EPI-NCSC and ESC, possibly explaining why EPI
      NCSC are not tumorigenic. Overall, as embryonic remnants in an adult location EPI
      NCSC show several attractive characteristics for future cell replacement therapy
      and/or biomedical engineering: Due to their ability to migrate, EPI-NCSC can be
      isolated as a highly pure population of multipotent stem cells by minimally
      invasive procedures. The cells can be expanded in vitro into millions of stem
      cells/progenitors and they share some characteristics with pluripotent stem cells
      without being tumorigenic. Since the patients' own EPI-NCSC could be used for
      autologous transplantation, this would avoid graft rejection.

PMID- 18712512
TI  - [Vertigo and falls in the elderly: Part 2: Fall diagnostics, prophylaxis and
      therapy].
AB  - In many acute or chronic vestibular diseases in old age, the risk of falling is
      increased. A fear of falling often develops together with further limitations to
      physical activity and subsequent physical and psychological consequences. Falls
      represent a substantial health-related risk factor. A regular balance, walking
      and muscle training is an effective prophylaxis. Components of the treatment of
      vestibular diseases in old age are counselling and encouragement (psychotherapy),
      treatment of the specific organic disease, specific vestibular rehabilitation and
      a symptomatic medication therapy. Vertigo in old age is a multifactorial process.
      The differential diagnosis of disorders of the equilibrium function in old age
      represents a challenge which can only be overcome by interdisciplinary
      cooperation.

PMID- 18712513
TI  - [From marker expression to individual therapy of patients with bladder cancer].
AB  - Urothelial carcinoma of the bladder is a tumor entity with a heterogenous
      clinical course. At one end of the spectrum, patients are treated for low-grade
      carcinomas, which are likely to reccur but show low rates of tumor progression.
      At the other end, patients suffer from noninvasive or early invasive high-grade
      carcinomas. In these cases, risk-adapted treatment decisions are more
      complicated. The following article gives an overview of research activities on
      bladder cancer with the aim to individualize treatment of patients with bladder
      cancer.

PMID- 18712511
TI  - [Preoperative fasting 2008: medical behaviour between empiricism and science].
AB  - Preoperative fasting aims at minimizing the risk of pulmonary aspiration.
      However, perioperative safety does not directly increase with the duration of
      total abstinence from food and liquids. The traditional principle "nil per os
      from midnight on", is based on insufficient data, overinterpretation and expert
      opinion. In fact, the total perioperative risk of a clinically relevant
      regurgitation of gastric content is low. Clear liquids are not stored within the
      stomach for a long time and in the healthy, a fasting period of 6 h allows the
      total passage of solid food. Identifying those patients with an increased risk of
      perioperative aspiration is still difficult. In particular, the impact of
      pregnancy, adipositas and diabetes, trauma, smoking, opioids and renal
      insufficiency has not been clarified. This lack of knowledge is reflected by
      national and international guidelines concerning preoperative fasting, which
      mention the "patient at risk" without defining it exactly. Abstention from clear
      liquids 2 h before and of solids 6 h before induction of anesthesia, is becoming
      increasingly more accepted. Feeding babies with breast milk appears to be
      tolerated 4 h before anesthesiological procedures.

PMID- 18712514
TI  - [Identification and validation of clinically relevant molecular alterations in
      prostate cancer].
AB  - Significant cellular alterations required for the development and progression of
      cancers are detectable at the molecular level and represent potential targets for
      gene-specific therapies. Modern chip techniques allow the parallel analysis of
      virtually all known human genes and proteins in a single experiment. Using modern
      high-throughput techniques, numerous potential new biomarkers for the diagnosis
      and prediction of prostate cancer have been identified. However, so far none of
      these markers has improved clinical practice. One of the most important
      challenges in the coming years is the extensive clinical validation of molecular
      data using clinically relevant end points. For this venture the pivotal
      prerequisite is the availability of large, comprehensively annotated and
      standardized high-quality bioresources.

PMID- 18712515
TI  - Development and fine mapping of three co-dominant SCAR markers linked to the M/m
      gene in the cucumber plant (Cucumis sativus L.).
AB  - Owing to its diverse sex types, the cucumber plant has been studied widely as a
      model for sex determination. In addition to environmental factors and plant
      hormones, three major genes-F/f, M/m, and A/a-regulate the sex types in the
      cucumber plant. By combining the bulked segregant analysis (BSA) and the sequence
      related amplified polymorphism (SRAP) technology, we identified eight markers
      linking to the M/m locus. Among them, the two closely linked SRAP markers
      flanking the M/m locus were the co-dominant marker ME1EM26 and the dominant
      marker ME1EM23. Further, the co-dominant marker ME8SA7 co-segregated with the M/m
      locus. With the chromosome walking method using the cucumber genomic bacterial
      artificial chromosome (BAC) library, we successfully developed a co-dominant SCAR
      marker S_ME1EM23 from the ME1EM23 sequence. Along with the other two co-dominant
      SCAR markers S_ME1EM26 and S_ME8SA7 (developed from ME1EM26 and ME8SA7,
      respectively) in a larger segregating population (900 individuals), the M/m locus
      was mapped between S_ME1EM26 (5.4 cM) and S_ME1EM23 (0.7 cM), and S_ME8SA7 co
      segregated with it.

PMID- 18712516
TI  - Contrasting population genetic structure and gene flow between Oryza rufipogon
      and Oryza nivara.
AB  - The cross compatible wild relatives of crops have furnished valuable genes for
      crop improvement. Understanding the genetics of these wild species may enhance
      their further use in breeding. In this study, sequence variation of the nuclear
      Lhs1 gene was used to investigate the population genetic structure and gene flow
      of Oryza rufipogon and O. nivara, two wild species most closely related to O.
      sativa. The two species diverge markedly in life history and mating system, with
      O. rufipogon being perennial and outcrossing and O. nivara being annual and
      predominantly inbreeding. Based on sequence data from 105 plants representing 11
      wild populations covering the entire geographic range of these wild species, we
      detected significantly higher nucleotide variation in O. rufipogon than in O.
      nivara at both the population and species levels. At the population level the
      diversity in O. rufipogon (Hd = 0.712; theta (sil) = 0.0017) is 2-3 folds higher
      than that in O. nivara (Hd = 0.306; theta (sil) = 0.0005). AMOVA partitioning
      indicated that genetic differentiation among O. nivara populations (78.2%) was
      much higher than that among O. rufipogon populations (52.3%). The different level
      of genetic diversity and contrasting population genetic structure between O.
      rufipogon and O. nivara might be explained by their distinct life histories and
      mating systems. Our simulation using IM models demonstrated significant gene flow
      from O. nivara to O. rufipogon, indicating a directional introgression from the
      annual and selfing species into the perennial and outcrossing species. The
      ongoing introgression has played an important role in shaping current patterns of
      genetic diversity of these two wild species.

PMID- 18712517
TI  - Perivascular fatty tissue at the brachial artery is linked to insulin resistance
      but not to local endothelial dysfunction.
AB  - AIMS/HYPOTHESIS: Different ectopic fat depots, such as visceral or hepatic fat,
      are known to affect whole body insulin sensitivity. It has recently been
      hypothesised that differences in perivascular adipose tissue (PVAT) mass around
      resistance vessels may also contribute to insulin resistance, possibly via direct
      vascular effects leading to reduced capillary cross-sectional area in the muscle,
      which in turn affects muscular blood flow and glucose uptake. Based on this, the
      aim of the present study was to test whether PVAT around conduit arteries (i.e.
      the brachial artery) influences NO bioavailability, expressed as flow-mediated
      dilation (FMD), or insulin sensitivity in humans in vivo. METHODS: Insulin
      sensitivity was measured by OGTT in all 95 participants (59 women, 36 men; median
      age 47 years, range 19-66 years) and by the gold standard, a euglycaemic
      hyperinsulinaemic clamp, in a randomly selected subgroup of 33 participants.
      Quantification of the different fat compartments, including PVAT around the
      brachial artery, was achieved by high-resolution magnetic resonance imaging (1.5
      T). Blood flow and FMD were measured at the brachial artery using high-resolution
      (13 MHz) ultrasound, after 5 min of forearm occlusion. RESULTS: PVAT was
      negatively correlated with insulin sensitivity and the post-ischaemic increase in
      blood flow. The association between PVAT and insulin sensitivity (r = -0.54, beta
      = -0.37, p = 0.009) was independent of age, sex, visceral adipose tissue, liver
      fat, BMI and further cardiovascular risk factors. No correlation could be
      detected between PVAT and local endothelial function. However, we observed an
      independent association between PVAT and post-ischaemic increase in blood flow (r
      = -0.241; beta = -1.69; p = 0.02). CONCLUSIONS/INTERPRETATION: PVAT seems to play
      an independent role in the pathogenesis of insulin resistance. This may be due to
      direct vascular effects influencing muscular blood flow.

PMID- 18712518
TI  - Magnetic microsphere-based methods to study the interaction of teicoplanin with
      peptides and bacteria.
AB  - Teicoplanin (teic) from Actinoplanes teichomyceticus is a glycopeptide antibiotic
      used to treat many gram-positive bacterial infections. Glycopeptide antibiotics
      inhibit bacterial growth by binding to carboxy-terminal D-Ala-D-Ala intermediates
      in the peptidoglycan of the cell wall of gram-positive bacteria. In this paper we
      report the derivatization of magnetic microspheres with teic (teic-microspheres).
      Fluorescence-based techniques have been developed to analyze the binding
      properties of the microspheres to two D-Ala-D-Ala terminus peptides. The
      dissociation constant for the binding of carboxyfluorescein-labeled D-Ala-D-Ala-D
      Ala to teic on microspheres was established via fluorimetry and flow cytometry
      and was determined to be 0.5 x 10(-6) and 3.0 x 10(-6) mol L(-1), respectively.
      The feasibility of utilizing microparticles with fluorescence methods to detect
      low levels (the limit of bacterial detection was determined to be 30 colon
      forming units; cfu) of gram-positive bacteria has been demonstrated. A simple
      microfluidic experiment is reported to demonstrate the possibility of developing
      microsphere-based affinity assays to study peptide-antibiotic interaction.

PMID- 18712519
TI  - Interaction between cat's claw and protease inhibitors atazanavir, ritonavir and
      saquinavir.

PMID- 18712520
TI  - The reported germline repertoire of human immunoglobulin kappa chain genes is
      relatively complete and accurate.
AB  - We describe a bioinformatic analysis of germline and rearranged immunoglobulin
      kappa chain (IGK) gene sequences, performed in order to assess the completeness
      and reliability of the reported IGK repertoire. In contrast to the reported heavy
      chain gene repertoire, which includes many dubious sequences, only five IGK
      variable gene (IGKV) alleles appear to have been reported in error. There was,
      however, insufficient evidence to justify removing these IGKV genes from the
      germline repertoire. Bioinformatic analysis of apparent mismatches between
      reported germline genes and 1,863 expressed IGK sequences suggested the existence
      of two unreported IGKV polymorphisms. Genomic screening of 12 individuals led to
      the confirmation of both of these polymorphisms, IGKV1-16*02 and IGKV2-30*02. We
      also show that in contrast to the heavy chain, the IGK repertoire is dominated by
      sequences that use just a handful of kappa variable (IGKV) and junction (IGKJ)
      gene pairs. There is also little modification of IGKV and IGKJ genes by the
      processes of exonuclease removal and N nucleotide addition. The expressed IGK
      repertoire therefore lacks diversity and the junction region is particularly
      constrained. Remarkably, the analysis of a dataset of 435 relatively unmutated
      rearranged kappa genes showed that ten amino acid sequences account for almost
      10% of the rearrangements, with identical sequences being derived from as many as
      seven independent sources. Such dominant sequences are likely to have important
      roles in the operation of the humoral immune response.

PMID- 18712521
TI  - Modeling of growth kinetics for Pseudomonas putida during toluene degradation.
AB  - Glucose has been often used as a secondary substrate to enhance the degradation
      of primary substrate as well as the increase of biomass, especially for the
      inhibitory range of substrate concentration. In this study, we investigated the
      effect of glucose concentration on growth kinetics of Pseudomonas putida during
      toluene degradation for a wide concentration range (60-250 mg/l). Batch microcosm
      studies were conducted in order to monitor bacterial growth for three different
      initial concentrations (2, 5, 10 mg/ml) of glucose for a given toluene
      concentration. Modeling of growth kinetics was also performed for each growth
      curve of glucose dose using both Monod and Haldane kinetics. Batch studies
      revealed that bacterial growth showed a distinct inhibitory phase above some
      limit (approximately 170 mg/l) for the lowest (2 mg/ml) glucose dose, but the
      degree of inhibition decreased as the glucose dose increased, leading to three
      different growth patterns. The bacterial growth followed each of the modified
      Wayman and Tseng, Wayman and Tseng, and Luong model as the glucose dose increased
      from 2 to 10 mg/ml. This indicates that glucose has a prominent influence on
      bacterial growth during toluene degradation and that different kinetics should be
      adopted for each broth condition.

PMID- 18712522
TI  - Novel missense mutation c.2685G>C (p.Q895H) in VWF gene associated with very low
      levels of VWF mRNA.
AB  - Homozygous patients for null alleles in VWF gene show a severe von Willebrand
      phenotype, whereas compound heterozygous patients only show the phenotype of the
      expressed allele. Five members of the same family were studied. The two patients
      showed borderline VWF levels, a mild factor VIII (FVIII) deficiency and a
      decrease of the binding of VWF to exogenous FVIII. The genetic analyses of the
      VWF gene confirmed that the patients were compound heterozygous for c.2561G>A
      (R854Q) and c.2685G>C (p.Q895H) mutations. The latter, is located in the 3'
      extreme of exon 20, and it has not been previously described. Studies of the cDNA
      from platelet mRNA were performed to investigate the expression of p.H895 allele.
      The loss of heterozygosity at the cDNA level suggests a lack of expression of the
      p.H895 allele. The overall studies can explain the type 2N phenotype of the two
      patients, since the allele carrying the new missense mutation p.Q895H has shown a
      low expression of VWF gene.

PMID- 18712524
TI  - Use of SSR markers to determine the anther-derived homozygous lines in coconut.
AB  - Anther culture was used to obtain dihaploid (DH) coconut plants and their ploidy
      level was determined by flow cytometric analysis. Simple sequence repeat (SSR)
      marker analysis was conducted to identify the homozygous diploid individuals.
      Ploidy analysis showed that 50% of the tested plantlets were haploid and 50% were
      diploid. Polymorphic fragments of the mother palm and their segregation patterns
      in anther-derived plantlets were used to determine the origin of the diploid
      plantlets. Using a diagnostic SSR marker (CNZ43), all the diploid plantlets
      tested were identified as being derived from microspores (i.e. were homozygous)
      and were thus candidates for use in coconut breeding programs.

PMID- 18712523
TI  - Infliximab-induced lupus-like syndrome in a patient with ankylosing spondylitis.
AB  - Infliximab is a chimerical monoclonal antibody currently used in the treatment of
      various inflammatory diseases. Lupus-like syndrome is a rarely reported adverse
      event, and generally observed in rheumatoid arthritis cases. We hereby define and
      describe a case of a lupus-like syndrome, which developed following the 4th
      infliximab infusion in a 62-year-old patient with ankylosing spondylitis (AS). As
      far as we acknowledge, the present case is the third AS case with infliximab
      induced lupus.

PMID- 18712525
TI  - The proton pump inhibitor inhibits cell growth and induces apoptosis in human
      hepatoblastoma.
AB  - PURPOSE: In normal physiology, a vacuolar-type proton pump (V-ATPase) maintains
      an intracellular acid microenvironment in lysosome, endosome, and other
      endomembrane systems. Cancer cells overexpress V-ATPase compared with normal
      cells, and disturbances of the acid environment are thought to significantly
      impact the cancer cell infiltration and growth. Bafilomycin A1 (Baf-A1) is a
      specific inhibitor of the proton-pump inhibitor (PPI) V-ATPase. Neoplastic cells
      are reportedly more sensitive to Baf-A1 than normal cells, and the difference
      between the susceptibility to Baf-A1 in normal cells and that in cancer cells may
      become a target in the cancer therapy. With this in mind, we used cells of
      hepatoblastoma, the cancer type accounting for 80% of all childhood liver
      cancers, to investigate the effects of Baf-A1 as an inducer of cancer cell
      apoptosis and inhibitor of cancer cell reproduction METHODS AND RESULTS: Electron
      microscopy showed significant morphological change of the hepatoblastoma cells of
      the Baf-A1-treated group compared with hepatoblastoma cells of the Baf-A1-free
      group. The rate of the apoptotic cell increased, and cell reproduction was
      inhibited. Moreover, the analysis of hepatoblastoma cells using the gene Chip
      gene expression analysis arrays showed that three of the 27 V-ATPase-related
      transcripts (ATP6V0D2, ATP6V1B1, and ATP6V0A1) were more weakly expressed in the
      Baf-A1-treated cells than in the Baf-A1-free cells. In normal human hepatic
      cells, on the other hand, the inhibition of cell growth of the Baf-A1-treated
      cells was negligible compared to that of the cells without Baf-A1 treatment. The
      result of apoptotic cell detection by morphological observations and flow
      cytometry revealed that Baf-A1 inhibits hepatoblastoma cellular reproduction by
      inducing apoptosis. On the other hand, the Baf-A1-conferred inhibition of cell
      growth was negligible in normal human hepatocytes CONCLUSION: The V-ATPase
      inhibitor Baf-A1 has been proven to selectively inhibit the reproduction and
      induce the apoptosis of hepatoblastoma cells without adversely influencing normal
      hepatic cells. With these effects, V-ATPase inhibitors may hold promise as
      therapeutic agents for hepatoblastoma. Given that three V-ATPase-related genes
      (ATP6V0D2, ATP6V1B1, and ATP6V0A1) were more weakly expressed in the
      hepatoblastoma cells of the Baf-A1-treated group than in the Baf-A1-free cells,
      drug development targeting V-ATPase gene of hepatoblastomas is expected.

PMID- 18712526
TI  - Managing prenatally diagnosed asymptomatic congenital cystic adenomatoid
      malformation.
AB  - AIM: To review our cases of congenital cystic adenomatoid malformation (CCAM)
      with special emphasis on the management of prenatally diagnosed asymptomatic CCAM
      (PDA-CCAM). METHODS: A total of 42 consecutive CCAM patients treated between 1990
      and 2008 at our institution and affiliated hospitals were divided into four
      groups, according to whether prenatal diagnosis was made [PD (+) or (-)], whether
      patients were symptomatic [S (+) or (-)], whether there was any increase in size
      observed radiologically [R (+) or (-)], and whether surgical resection was
      performed [X (+) or (-)], to give a symptomatic early surgery group diagnosed
      prenatally (group A; n = 15): PD (+), S (+), R (+), X (+); an asymptomatic early
      surgery group diagnosed prenatally (group B; n = 8): PD (+), S (-), R (-), X (+);
      a conservative observation group diagnosed prenatally (group C; n = 6): PD (+), S
      (-), R (-), X (-); and a symptomatic surgery group diagnosed postnatally (group
      D; n = 13): PD (-), S (+), R (unknown), X (+). Patient demographics, effects of
      surgical stress, histopathology, and outcome were compared between the four
      groups. RESULTS: Groups A and B had surgery as neonates and mean duration of post
      operative follow-up has been 15.7 months for group A and 63.3 months for group B.
      Group C has been under observation for a mean of 21.6 months (range: 10-40
      months) with no incidence of infection. In group D, four had surgery as neonates
      after developing respiratory distress, and nine had surgery later (mean age: 4.1
      years) after developing pneumonia (late onset group). Mean duration of follow-up
      for group D has been 48.0 months. In the late-onset group, pneumonia was
      successfully treated medically, and all nine had elective surgery with no intra-
      or post-operative complications. However, compared with group B (asymptomatic
      early surgery group diagnosed prenatally) the late-onset group had significantly
      longer duration of surgery (P < 0.05), significantly greater intraoperative blood
      loss (P < 0.01), and significantly higher peak post-operative C-reactive protein
      (P < 0.01), although there were no statistical differences for increase in white
      blood cell count ratios or length of hospitalization. Malignancy has not
      developed to date in any subject. CONCLUSION: Our data suggest that patients with
      PDA-CCAM may be observed safely until they become symptomatic or changes in size
      are observed radiologically.

PMID- 18712527
TI  - Efficacy and safety of balloon-occluded retrograde transvenous obliteration for
      gastric fundal varices in children.
AB  - Balloon-occluded retrograde transvenous obliteration (B-RTO) is an interventional
      radiologic technique that obliterates gastric fundal varices (GFV) from draining
      veins under balloon occlusion. Few reports have described the use of B-RTO in
      children. Here, we report a case of B-RTO in a 2-year-old female patient with
      isolated huge varices in the gastric fundus associated with portal hypertension
      after surgery for biliary atresia. There was no complication and thrombosis of
      the varices was achieved. Our results demonstrate that B-RTO is an efficacious
      and safe treatment for children with isolated GFV.

PMID- 18712528
TI  - Acute pancolitis after colonoscopy in liver cirrhosis patient.

PMID- 18712529
TI  - Identification of stage-specific larval camouflage associated genes in the
      swallowtail butterfly, Papilio xuthus.
AB  - The swallowtail butterfly Papilio xuthus changes its larval body pattern
      dramatically during the fourth ecdysis. The penultimate (fourth) instar larvae
      mimic bird droppings that have many tubercle structures on their surface, whereas
      the final (fifth) instar larvae have a green camouflage color. To identify the
      genes involved in stage-specific larval mimicry markings, we compared the
      epidermal messenger ribonucleic acid expression between the third and fourth
      molts of P. xuthus using a complementary deoxyribonucleic acid subtraction
      method. After analyzing 2,072 clones from two subtractive libraries, we obtained
      31 and 64 candidate genes for final (Fsg) or penultimate instar-specific genes
      (Psg), respectively. The expression pattern of each gene was examined by reverse
      transcriptase polymerase chain reaction and in situ hybridization. Among Fsgs,
      Fsg02 and Fsg20 were expressed in the presumptive green region only during the
      fourth molt, suggesting that these two genes were correlated with green
      coloration in the final instar. Among Psgs, 11 cuticular protein genes were
      expressed specifically in the tubercle structures during the third molt. These
      genes are likely to be involved in the formation of the unique tubercle
      structures observed in the juvenile instar. We found that genes with similar
      expression patterns do not necessarily share the same protein motifs and vice
      versa. This study provides novel molecular markers and insights into the
      molecular mechanisms of the larval color pattern and body shape.

PMID- 18712530
TI  - Angiostrongylus costaricensis (Nematoda: Protostrongylidae): migration route in
      experimental infection of Omalonyx sp. (Gastropoda: Succineidae).
AB  - Angiostrongylus costaricensis can infect several mollusks, and its migration
      route in intermediate hosts has been studied only in Sarasinula marginata. To
      verify the susceptibility of Omalonyx sp. as an intermediate host of A.
      costaricensis and to analyze the nematode migration route, individuals were
      infected with stage 1 larvae. Obtained stage 3 larvae were orally inoculated in
      mice, and after 30 days, adult worms and stage 1 larvae were recovered,
      demonstrating Omalonyx susceptibility and suitability to infection. To define the
      parasite migration routes, specimens of Omalonyx with 30 min, 1 h, 2 h, 4 h, 6 h,
      8 h, 2 days, 5 days, 10 days, 12 days, 15 days, 20 days, 21 days, 25 days, 28
      days, and 30 days of infection were fixed and serially sectioned. Histological
      sections were stained with hematoxylin-eosin. The results were compared to those
      described in S. marginata. Oral and cutaneous infections were noted. After the
      penetration, larvae were retained, mainly in the fibromuscular tissue, by
      hemocytes, or they spread to the whole organism through the circulation,
      following the anatomical structure of the vasculature. The perilarval hemocyte
      reaction in Omalonyx was more intense until stage 2 larva instar, decreasing in
      the presence of stage 3 larvae. Differences in some aspects of hemocyte reaction
      between S. marginata and Omalonyx exemplify interspecific peculiarities in snail
      response to the same parasite.

PMID- 18712531
TI  - Relative quantity judgment by Asian elephants (Elephas maximus).
AB  - This study investigated whether Asian elephants can make relative quantity
      judgment (RQJ), a dichotomous judgment of unequal quantities ordered in
      magnitude. In Experiment 1, elephants were simultaneously shown two baskets with
      differing quantities of bait (up to 6 items). In Experiment 2, elephants were
      sequentially presented with baits, which could not be seen by elephants in their
      total quantities. The task of elephants was to choose the larger quantity in both
      experiments. Results showed that the elephants chose the larger quantity with
      significantly greater frequency. Interestingly, the elephants did not exhibit
      disparity or magnitude effects, in which performance declines with a smaller
      difference between quantities in a two-choice task, or the total quantity
      increases, respectively. These findings appear to be inconsistent with the
      previous reports of RQJ in other animals, suggesting that elephants may be using
      a different mechanism to compare and represent quantities than previously
      suggested for other species.

PMID- 18712532
TI  - An assessment of memory awareness in tufted capuchin monkeys (Cebus apella).
AB  - Humans, apes, and rhesus monkeys demonstrate memory awareness by collecting
      information when ignorant and acting immediately when informed. In this study,
      five capuchin monkeys searched for food after either watching the experimenter
      bait one of four opaque tubes (seen trials), or not watching (unseen trials).
      Monkeys with memory awareness should look into the tubes before making a
      selection only on unseen trials because on seen trials they already know the
      location of the food. In Experiment 1, one of the five capuchins looked
      significantly more often on unseen trials. In Experiment 2, we ensured that the
      monkeys attended to the baiting by interleaving training and test sessions. Three
      of the five monkeys looked more often on unseen trials. Because monkeys looked
      more often than not on both trial types, potentially creating a ceiling effect,
      we increased the effort required to look in Experiment 3, and predicted a larger
      difference in the probability of looking between seen and unseen trials. None of
      the five monkeys looked more often on unseen trials. These findings provide
      equivocal evidence for memory awareness in capuchin monkeys using tests that have
      yielded clear evidence in humans, apes, and rhesus monkeys.

PMID- 18712533
TI  - Application of FT-IR spectroscopy for control of the medium composition during
      the biodegradation of nitro aromatic compounds.
AB  - Previous studies showed that cabbage leaf extract (CLE) added to the growth
      medium can noticeably promote the degradation of nitro aromatic compounds by
      specific consortium of bacteria upon their growth. For further development of the
      approach for contaminated soil remediation it was necessary to evaluate the
      qualitative and/or quantitative composition of different origin CLE and their
      relevance on the growth of explosives-degrading bacteria. Six CLE (different by
      species, cultivars and harvesting time) were tested and used as additives to the
      growth medium. It was shown that nitro aromatic compounds can be identified in
      the FT-IR absorption spectra by the characteristic band at 1,527 cm(-1), and in
      CLE by the characteristic band at 1,602 cm(-1). The intensity of the CLE band at
      1,602 cm(-1) correlated with the concentration of total nitrogen (R2=0.87) and
      decreased upon the growth of bacteria. The content of nitrogen in CLE differed
      (0.22-1.00 vol.%) and significantly influenced the content of total carbohydrates
      (9.50-16.00% DW) and lipids [3.90-9.90% dry weight (DW)] accumulated in bacterial
      cells while the content of proteins was similar in all samples. Though this study
      showed quantitative differences in the composition of the studied CLE and the
      response of bacterial cells to the composition of the growth media, and proved
      the potential of this additive for remediation of contaminated soil. It was shown
      that analysis of CLE and monitoring of the conversion of nitro aromatic compounds
      can be investigated by FT-IR spectroscopy as well as by conventional chemical
      methods.

PMID- 18712534
TI  - Effect of plant extract on the degradation of nitroaromatic compounds by soil
      microorganisms.
AB  - Remediation of soils contaminated by nitroaromatic compounds and nitramines, i.e.
      explosives, is known as very important, complicated, and rapidly developing area
      of biotechnology. A search for optimal growth conditions for soil bacteria is of
      a great importance in order to isolate various xenobiotic degraders. Bacteria
      consortium A43 was isolated from soils contaminated with explosives. In the
      presence of carbohydrate and plant extract, an addition of TNT to the solidified
      minimal medium stimulated the growth of the tested bacteria, as compared to other
      bacteria consortium isolated from the same soils. Reducing sugars as
      carbohydrates, and cabbage leaf extract as a plant extract were used in these
      experiments. Cultivation of the A43 in liquid medium of the same content showed
      that addition of cabbage leaf extract alone to medium is much more efficient for
      TNT degradation by growing biomass as compared to addition of carbohydrate alone.

PMID- 18712535
TI  - The use of magnesium peroxide for the inhibition of sulfate-reducing bacteria
      under anoxic conditions.
AB  - Sulfate-reducing bacteria (SRB), which cause microbiologically influenced
      material corrosion under anoxic conditions, form one of the major groups of
      microorganisms responsible for the generation of hydrogen sulfide. In this study,
      which is aimed at reducing the presence of SRB, a novel alternative approach
      involving the addition of magnesium peroxide (MgO2) compounds involving the use
      of reagent-grade MgO2 and a commercial product (ORC) was evaluated as a means of
      inhibiting SRB in laboratory batch columns. Different concentrations of MgO2 were
      added in the columns when black sulfide sediment had appeared in the columns. The
      experimental results showed that MgO2 is able to inhibit biogenic sulfide. The
      number of SRB, the sulfide concentration and the sulfate reducing rate (SRR) were
      decreased. ORCtrade mark as an additive was able to decrease more effectively the
      concentration of sulfide in water and the SRB-control effect was maintained over
      a longer time period when ORCtrade mark was used. The level of oxidation
      reduction potential (ORP), which has a linear relationship to the sulfide/sulfate
      ratio, is a good indicator of SRB activity. As determined by fluorescence in-situ
      hybridization (FISH), most SRB growth was inhibited under increasing amounts of
      added MgO2. The concentration of sulfide reflected the abundance of the SRB.
      Utilization of organic matter greater than the theoretical SRB utilization rate
      indicated that facultative heterotrophs became dominant after MgO2 was added. The
      results of this study could supply the useful information for further study on
      evaluating the solution to biocorrosion problems in practical situations.

PMID- 18712536
TI  - Colorimetric assay for biofilms in wet processing conditions.
AB  - Controlling bacterial biofilms is necessary for food safety and industrial
      processing in clean room environments. Our goal was to develop a method to
      quantitatively measure biofilm produced by pathogens under wet poultry production
      and processing conditions. Stainless steel and glass coupons were incubated in
      aqueous media containing reduced nutrients and exposed to Listeria monocytogenes
      under static temperature and humidity conditions. Samples were measured
      separately by biofilm assay and viable cell density, and then confirmed by
      spectrophotometry and microscopy. The biofilm assay resulted in different t
      groupings from the cell density. The mean from the biofilm assay was 0.50, and
      the error% was 0.595. The mean of the log10 density (cfu/cm2) was 5.90, and the
      standard deviation ranged from 0.127 to 0.438 on 24 coupons. The typical sequence
      of biofilm development, followed by microscopy of biofilm grown on glass coupons,
      exhibited a change from dispersed single cells to an all-over pattern of clumps
      with few dispersed cells. L. monocytogenes formed biofilms on all of the
      substrata tested. Bacterial counts from planktonic cultures at 24, 48, 72, and
      144 h confirmed that L. monocytogenes remained viable throughout the experiment
      and reached equilibrium between 6 and 24 h. The cell density log10/ml was 8.01,
      8.03, 7.69, and 6.66, respectively; and the standard deviation ranged from 0.156
      to 0.394. The data will be used to grow stable biofilms of Listeria spp.
      collected from the food processing environment for further study. This is the
      first use of the crystal violet assay for measurement of bacterial biofilms on
      stainless steel under these conditions. The methods tested are applicable to
      other bacteria and substrata.

PMID- 18712537
TI  - Expression, purification and immobilization of the intracellular invertase INVA,
      from Zymomonas mobilis on crystalline cellulose and Nylon-6.
AB  - This paper presents two immobilization methods for the intracellular invertase
      (INVA), from Zymomonas mobilis. In the first method, a chimeric protein
      containing the invertase INVA, fused through its C-terminus to CBDCex from
      Cellulomonas fimi was expressed in Escherichia coli strain BL21 (DE3). INVA was
      purified and immobilized on crystalline cellulose (Avicel) by means of affinity,
      in a single step. No changes were detected in optimal pH and temperature when
      INVA-CBD was immobilized on Avicel, where values of 5.5 and 30 degrees C,
      respectively, were registered. The kinetic parameters of the INVA-CBD fusion
      protein were determined in both its free form and when immobilized on Avicel. Km
      and Vmax were affected with immobilization, since both showed an increase of up
      to threefold. Additionally, we found that subsequent to immobilization, the INVA
      CBD fusion protein was 39% more susceptible to substrate inhibition than INVA-CBD
      in its free form. The second method of immobilization was achieved by the
      expression of a 6xHis-tagged invertase purified on Ni-NTA resin, which was then
      immobilized on Nylon-6 by covalent binding. An optimal pH of 5.5 and a
      temperature of 30 degrees C were maintained, subsequent to immobilization on
      Nylon-6 as well as with immobilization on crystalline cellulose. The kinetic
      parameters relating to Vmax increased up to 5.7-fold, following immobilization,
      whereas Km increased up to 1.7-fold. The two methods were compared showing that
      when invertase was immobilized on Nylon-6, its activity was 1.9 times that when
      immobilized on cellulose for substrate concentrations ranging from 30 to 390 mM
      of sucrose.

PMID- 18712538
TI  - Photodynamic inactivation of recombinant bioluminescent Escherichia coli by
      cationic porphyrins under artificial and solar irradiation.
AB  - A faster and simpler method to monitor the photoinactivation process of
      Escherichia coli involving the use of recombinant bioluminescent bacteria is
      described here. Escherichia coli cells were transformed with luxCDABE genes from
      the marine bioluminescent bacterium Vibrio fischeri and the recombinant
      bioluminescent indicator strain was used to assess, in real time, the effect of
      three cationic meso-substituted porphyrin derivatives on their metabolic
      activity, under artificial (40 W m(-2)) and solar irradiation (approximately 620
      W m(-2)). The photoinactivation of bioluminescent E. coli is effective (>4 log
      bioluminescence decrease) with the three porphyrins used, the tricationic
      porphyrin Tri-Py+-Me-PF being the most efficient compound. The photoinactivation
      process is efficient both with solar and artificial light, for the three
      porphyrins tested. The results show that bioluminescence analysis is an efficient
      and sensitive approach being, in addition, more affordable, faster, cheaper and
      much less laborious than conventional methods. This approach can be used as a
      screening method for bacterial photoinactivation studies in vitro and also for
      the monitoring of the efficiency of novel photosensitizer molecules. As far as we
      know, this is the first study involving the use of bioluminescent bacteria to
      monitor the antibacterial activity of porphyrins under environmental conditions.

PMID- 18712540
TI  - Effects of water potential on spore germination and viability of Fusarium
      species.
AB  - Germination of macroconidia and/or microconidia of 24 strains of Fusarium solani,
      F. chlamydosporum, F. culmorum, F. equiseti, F. verticillioides, F. sambucinum,
      F. oxysporum and F. proliferatum isolated from fluvial channels and sea beds of
      the south-eastern coast of Spain, and three control strains (F. oxysporum
      isolated from affected cultures) was studied in distilled water in response to a
      range of water potentials adjusted with NaCl. (0, -13.79, -41.79, -70.37, -99.56
      and -144.54 bars). The viability (UFC/ml) of suspensions was also tested in three
      time periods (0, 24 and 48 h). Conidia always germinated in distilled water. The
      pattern of conidial germination observed of F. verticilloides, F. oxysporum, F.
      proliferatum, F. chlamydosporum and F. culmorum was similar. A great diminution
      of spore germination was found in -13.79 bars solutions. Spore germination
      percentage for F. solani isolates was maximal at 48 h and -13.79 bars with 21.33%
      spore germination, 16% higher than germination in distilled water. F. equiseti
      shows the maximum germination percentage in -144.54 bars solution in 24 h time
      with 12.36% germination. This results did not agree with those obtained in the
      viability test were maximum germination was found in distilled water. The
      viability analysis showed the great capacity of F. verticilloides strains to form
      viable colonies, even in such extreme conditions as -144.54 bars after 24 h F.
      proliferatum colony formation was prevented in the range of -70.37 bars. These
      results show the clear affectation of water potential to conidia germination of
      Fusaria. The ability of certain species of Fusarium to develop a saprophytic life
      in the salt water of the Mediterranean Sea could be certain. Successful
      germination, even under high salty media conditions, suggests that Fusarium spp.
      could have a competitive advantage over other soil fungi in crops irrigated with
      saline water. In the specific case of F. solani, water potential of -13.79 bars
      affected germination positively. It could indicate that F. solani has an special
      physiological mechanism of survival in low water potential environments.

PMID- 18712539
TI  - Pneumococcal whole-cell vaccine: optimization of cell growth of unencapsulated
      Streptococcus pneumoniae in bioreactor using animal-free medium.
AB  - The high cost of the available pneumococcal conjugated vaccines has been an
      obstacle in implementing vaccination programs for children in developing
      countries. As an alternative, Malley et al. proposed a vaccine consisting of
      inactivated whole-cells of unencapsulated S. pneumoniae, which provides serotype
      independent protection and involves lower production costs. Although the
      pneumococcus has been extensively studied, little research has focused on its
      large-scale culture, thus implying a lack of knowledge of process parameters,
      which in turn are essential for its successful industrial production. The strain
      Rx1Al- eryR was originally cultured in Todd-Hewitt medium (THY), which is
      normally used for pneumococcus isolation, but is unsuitable for human vaccine
      preparations. The purposes of this study were to compare the strains Rx1Al- eryR
      and kanR, develop a new medium, and generate new data parameters for scaling-up
      the process. In static flasks, cell densities were higher for eryR than kanR. In
      contrast, the optical density (OD) of the former decreased immediately after
      reaching the stationary phase, and the OD of the latter remained stable. The
      strain Rx1Al- kanR was cultivated in bioreactors with medium based on either acid
      hydrolyzed casein (AHC) or enzymatically hydrolyzed soybean meal (EHS). Biomass
      production in EHS was 2.5 times higher than in AHC, and about ten times higher
      than in THY. The process developed for growing the strain Rx1Al- kanR in pH
      controlled bioreactors was shown to be satisfactory to this fastidious bacterium.
      The new culture conditions using this animal-free medium may allow the production
      of the pneumococcal whole-cell vaccine.

PMID- 18712541
TI  - The interactive effects of temperature and osmotic potential on the growth of
      marine isolates of Fusarium solani.
AB  - The mycelial growth of 18 Fusarium solani strains isolated from sea beds of the
      south-eastern coast of Spain was tested on potato-dextrose-agar adjusted to
      different osmotic potentials with either KCl or NaCl (-1.50 to -144.54 bars) in
      10 degrees C intervals ranging from 15 to 35 degrees C. Fungal growth was
      determined by measuring colony diameter after 4 days of incubation. Mycelial
      growth was maximal at 25 degrees C. The quantity and frequency pattern of
      mycelial growth of F. solani differ significantly at 15 and 25 degrees C, with
      maximal growth occurring at the highest water potential tested (-1.50 bars); and
      at 35 degrees C, with a maximal mycelial growth at -13.79 bars. The effect of
      water potential was independent of salt composition. The general growth pattern
      of F. solani showed declining growth at potentials below -41.79 bars. Fungal
      growth at 35 degrees C was always higher than that grow at 15 degrees C, of all
      the water potentials tested. Significant differences observed in the response of
      mycelia to water potential and temperature as main and interactive effects. The
      viability of cultures was increasingly inhibited as the water potential dropped,
      but some growth was still observed at -99.56 bars. These findings could indicate
      that marine strains of F. solani have a physiological mechanism that permits
      survival in environments with low water potential. The observed differences in
      viability and the magnitude of growth could indicate that the biological factors
      governing potential and actual growth are affected by osmotic potential in
      different ways.

PMID- 18712542
TI  - Kinetics of Bacillus thuringiensis var. israelensis growth on high glucose
      concentrations.
AB  - The kinetic and general growth features of Bacillus thuringiensis var.
      israelensis were evaluated. Initial glucose concentration (S0) in fermentation
      media varied from 10 to 152 g/l. The results afforded to characterize four
      morphologically and physiologically well-defined culture phases, independent of
      S0 values: Phase I, vegetative growth; Phase II, transition to sporulation; Phase
      III, sporulation; and Phase IV, spores maturation and cell lysis. Important
      process parameters were also determined. The maximum specific growth rates
      (microX,m) were not affected with S0 up to 75 g/l (1.0-1.1 per hour), but higher
      glucose concentrations resulted in growth inhibition by substrate, revealed by a
      reduction in microX,m values. These higher S0 values led to longer Phases III and
      IV and delayed sporulation. Similar biomass concentrations (Xm=15.2-15.9 g/l)
      were achieved with S0 over 30.8 g/l, with increasing residual substrate,
      suggesting a limitation in some other nutrients and the use of glucose to form
      other metabolites. In this case, with S0 from 30.8 to 152 g/l, cell yield (YX/S)
      decreased from 0.58 to 0.41 g/g. On the other hand, with S0=10 g/l growth was
      limited by substrate, and YX/S has shown its maximum value (0.83 g/g).

PMID- 18712543
TI  - Decolorization of textile dye by Candida albicans isolated from industrial
      effluents.
AB  - The aim of the present work was to observe microbial decolorization and
      biodegradation of the Direct Violet 51 azo dye by Candida albicans isolated from
      industrial effluents and study the metabolites formed after degradation. C.
      albicans was used in the removal of the dye in order to further biosorption and
      biodegradation at different pH values in aqueous solutions. A comparative study
      of biodegradation analysis was carried out using UV-vis and FTIR spectroscopy,
      which revealed significant changes in peak positions when compared to the dye
      spectrum. Theses changes in dye structure appeared after 72 h at pH 2.50; after
      240 h at pH 4.50; and after 280 h at pH 6.50, indicating the different by
      products formed during the biodegradation process. Hence, the yeast C. albicans
      was able to remove the color substance, demonstrating a potential enzymatic
      capacity to modify the chemical structure of pigments found in industrial
      effluents.

PMID- 18712544
TI  - Conjugated linoleic acid producing potential of lactobacilli isolated from the
      rumen of cattle.
AB  - Lactobacilli isolated from the rumen of cattle were subjected to morphological
      and biochemical characterizations followed by PCR-based identification. Among
      isolates, Lactobacillus brevis was found to be the most prevalent species in the
      rumen. For in vitro conjugated linoleic acid (CLA) production, the two isolates
      of L. brevis and one each of Lactobacillus viridescens and Lactobacillus lactis
      were selected. The sunflower oil (i.e., 0.25, 0.5 and 1.0%; a rich source of
      linoleic acid) was added to skim milk as a substrate for CLA production by
      isolates at 37 degrees C/12 h. L. brevis 02 was found to be the most potential
      CLA producer (10.53 mg CLA/g fat) at 0.25% concentration of sunflower oil
      followed by L. brevis 01 (8.27 mg CLA/g fat). However, at higher level of
      sunflower oil (i.e., 1.0%), L. lactis was the highest CLA producer (9.22 mg/g
      fat) when compared to L. brevis and L. viridescens. The results indicated that L.
      brevis and/or CLA production was inhibited with increasing concentration of
      sunflower oil in skim milk. In contrast, L. lactis and L. viridescens could
      tolerate the increasing concentrations of sunflower oil and produced higher CLA.
      Overall, L. brevis extends a possibility to be used as a direct-fed microbial for
      ruminants to increase the CLA content in milk, however, in vivo trials are needed
      for validation of results obtained.

PMID- 18712545
TI  - Purification of capsular polysaccharide produced by Haemophilus influenzae type b
      through a simple, efficient and suitable method for scale-up.
AB  - Haemophilus influenzae type b, an encapsulated bacterium, causes meningitis in
      infants worldwide. The capsular polysaccharide conjugated to a carrier protein is
      effective in the prevention of such infections. The traditional purification
      process of polysaccharide from bacterial cultures for vaccine production is based
      on several selective precipitations with solvents such as: ethanol, phenol, and
      cationic detergents. The separations of solid and liquid phases are based on
      continuous centrifugation in explosion proof installations. The
      lipopolysaccharides are separated by ultracentrifugation. A simple and efficient
      method that can easily be scaled-up was developed for purification of
      polysaccharides. The ethanol precipitation was reduced to only two steps. The
      phenol treatment was substituted by ultrafiltration and enzymatic digestion.
      Lipopolysaccharide was removed by ultrafiltration together with addition of
      detergent and chelating agent.

PMID- 18712546
TI  - Characterization of new isolated Ralstonia eutropha strain A-04 and kinetic study
      of biodegradable copolyester poly(3-hydroxybutyrate-co-4-hydroxybutyrate)
      production.
AB  - A new isolated bacterial strain A-04 capable of producing high content of
      polyhydroxyalkanoates (PHAs) was morphologically and taxonomically identified
      based on biochemical tests and 16S rRNA gene analysis. The isolate is a member of
      the genus Ralstonia and close to Ralstonia eutropha. Hence, this study has led to
      the finding of a new and unexplored R. eutropha strain A-04 capable of producing
      PHAs with reasonable yield. The kinetic study of poly(3-hydroxybutyrate-co-4
      hydroxybutyrate) [P(3HB-co-4HB)] production by the R. eutropha strain A-04 was
      examined using butyric acid and gamma-hydroxybutyric acid as carbon sources.
      Effects of substrate ratio and mole ratio of carbon to nitrogen (C/N) on kinetic
      parameters were investigated in shake flask fed-batch cultivation. When C/N was
      200, that is, nitrogen deficient condition, the specific production rate of 3
      hydroxybutyrate (3HB) showed the highest value, whereas when C/N was in the range
      between 4 and 20, the maximum specific production rate of 4-hydroxybutyrate (4HB)
      was obtained. Thus, the synthesis of 3HB was growth-limited production under
      nitrogen-deficient condition, whereas the synthesis of 4HB was growth-associated
      production under nitrogen-sufficient condition. The mole fraction of 4HB units
      increased proportionally as the ratio of gamma-hydroxybutyric acid in the feed
      medium increased at any value of C/N ratio. Based on these kinetic studies, a
      simple strategy to improve P(3HB-co-4HB) production in shake flask fed-batch
      cultivation was investigated using C/N and substrate feeding ratio as
      manipulating variable, and was successfully proved by the experiments.

PMID- 18712547
TI  - Immobilization of the recombinant invertase INVB from Zymomonas mobilis on Nylon
      6.
AB  - The recombinant invertase INVB (re-INVB) from Zymomonas mobilis was immobilized
      on microbeads of Nylon-6, by means of covalent bonding. The enzyme was strongly
      and successfully bound to the support. The activity of the free and immobilized
      enzyme was determined, using 10% (w/v) sucrose, at a temperature ranging between
      15 and 60 degrees C and a pH ranging between 3.5 and 7. The optimal pH and
      temperature for the immobilized enzyme were 5.5 and 25 degrees C, respectively.
      Immobilization of re-INVB on Nylon-6 showed no significant change in the optimal
      pH, but a difference in the optimal temperature was evident, as that for the free
      enzyme was shown to be 40 degrees C. The values for kinetic parameters were
      determined as: 984 and 98 mM for Kappm of immobilized and free re-INVB,
      respectively. Kappcat values for immobilized and free enzymes were 6.1x10(2) and
      1.2x10(4) s(-1), respectively, and immobilized re-INVB showed Vappmax of 158.73
      micromol h min(-1) mg(-1). Immobilization of re-INVB on Nylon-6 enhanced the
      thermostability of the enzyme by 50% at 30 degrees C and 70% at 40 degrees C,
      when compared to the free enzyme. The immobilization system reported here may
      have future biotechnological applications, owing to the simplicity of the
      immobilization technique, the strong binding of re-INVB to the support and the
      effective thermostability of the enzyme.

PMID- 18712549
TI  - Characterization of biofilm formation on a humic material.
AB  - Biofilms are major sites of carbon cycling in streams. Therefore, it is crucial
      to improve knowledge about biofilms' structure and microbial composition to
      understand their contribution in the self-purification of surface water. The
      present work intends to study biofilm formation in the presence of humic
      substances (HSs) as a carbon source. Two biofilm flowcells were operated in
      parallel; one with synthetic stream water, displaying a background carbon
      concentration of 1.26+/-0.84 mg L(-1), the other with added HSs and an overall
      carbon concentration of 9.68+/-1.00 mg L(-1). From the biofilms' results of
      culturable and total countable cells, it can be concluded that the presence of
      HSs did not significantly enhance the biofilm cell density. However, the biofilm
      formed in the presence of HSs presented slightly higher values of volatile
      suspended solids (VSS) and protein. One possible explanation for this result is
      that HSs adsorbed to the polymeric matrix of the biofilm and were included in the
      quantification of VSS and protein. The microbial composition of the biofilm with
      addition of HSs was characterized by the presence of bacteria belonging to beta
      Proteobacteria, Cupriavidus metallidurans and several species of the genus
      Ralstonia were identified, and gamma-Proteobacteria, represented by Escherichia
      coli. In the biofilm formed without HSs addition beta-Proteobacteria, represented
      by the species Variovorax paradoxus, and bacteria belonging to the group
      Bacteroidetes were detected. In conclusion, the presence of HSs did not
      significantly enhance biofilm cell density but influenced the bacterial diversity
      in the biofilm.

PMID- 18712548
TI  - Modulation of tolerance to Cr(VI) and Cr(VI) reduction by sulfate ion in a
      Candida yeast strain isolated from tannery wastewater.
AB  - The main aim of this study was to investigate the influence of the sulfate ion on
      the tolerance to Cr(VI) and the Cr(VI) reduction in a yeast strain isolated from
      tannery wastewater and identified as Candida sp. FGSFEP by the D1/D2 domain
      sequence of the 26S rRNA gene. The Candida sp. FGSFEP strain was grown in culture
      media with sulfate concentrations ranging from 0 to 23.92 mM, in absence and
      presence of Cr(VI) [1.7 and 3.3 mM]. In absence of Cr(VI), the yeast specific
      growth rate was practically the same in every sulfate concentration tested, which
      suggests that sulfate had no stimulating or inhibiting effect on the yeast cell
      growth. In contrast, at the two initial Cr(VI) concentrations assayed, the
      specific growth rate of Candida sp. FGSFEP rose when sulfate concentration
      increased. Likewise, the greater efficiencies and volumetric rates of Cr(VI)
      reduction exhibited by Candida sp. FGSFEP were obtained at high sulfate
      concentrations. Yeast was capable of reducing 100% of 1.7 mM Cr(VI) and 84% of
      3.3 mM Cr(VI), with rates of 0.98 and 0.44 mg Cr(VI)/L h, with 10 and 23.92 mM
      sulfate concentrations, respectively. These results indicate that sulfate plays
      an important role in the tolerance to Cr(VI) and Cr(VI) reduction in Candida sp.
      FGSFEP. These findings may have significant implications in the biological
      treatment of Cr(VI)-laden wastewaters.

PMID- 18712550
TI  - Assessment of physiological state of microorganisms in activated sludge with flow
      cytometry: application for monitoring sludge production minimization.
AB  - Many sludge reduction processes have been studied for the minimization of sludge
      production in biological wastewater treatment. The investigations on most of
      these processes have monitored the increase of the soluble chemical oxygen
      demand, the sludge mass reduction, or the decrease of the floc size, but little
      information has been obtained on cell lysis and the change of the biological cell
      activity. However, employing any strategy for reducing sludge production may have
      an impact of microbial community in biological wastewater treatment process. This
      impact may influence the sludge characteristics and the quality of effluent. The
      objective of this study concerns the determination of the physiological state of
      activated sludge microorganisms during a sludge minimization process. A thermal
      treatment at 80 degrees C for 5, 20, 40 and 60 min was chosen in this study.
      Staining bacteria with CTC and SYTOX green was used to evaluate biological cell
      activity and viability of cell types contained in activated sludge, respectively.
      The monitoring of cell activity and viability was performed using flow cytometry
      (FCM) analysis before and after thermal treatment of activated sludge. Results
      indicated an increase in the number of permeabilized cells and a decrease in the
      number of active cells, subsequent to the thermal treatment. The study also
      confirms the potential of FCM to successfully evaluate the physiological
      heterogeneity of an activated sludge bacterial population. Moreover, the
      experimentally observed correlations between the FCM results and the organic
      matter solubilization in activated sludge samples during thermal treatment
      revealed that the increase in the soluble organic matter concentration was
      predominantly due to an intracellular material release. Identifying the increase
      in activated sludge hydrolysis requires a precise knowledge of the involved
      mechanisms, and this study indicated that the FCM, used in conjunction with
      specific probes, could be a useful tool.

PMID- 18712551
TI  - Production of ethanol by filamentous and yeast-like forms of Mucor indicus from
      fructose, glucose, sucrose, and molasses.
AB  - The fungus Mucor indicus is found in this study able to consume glucose and
      fructose, but not sucrose in fermentation of sugarcane and sugar beet molasses.
      This might be an advantage in industries which want to selectively remove glucose
      and fructose for crystallisation of sucrose present in the molasses. On the other
      hand, the fungus assimilated sucrose after hydrolysis by the enzyme invertase.
      The fungus efficiently grew on glucose and fructose and produced ethanol in
      synthetic media or from molasses. The cultivations were carried out aerobically
      and anaerobically, and manipulated toward filamentous or yeast-like morphology.
      Ethanol was the major metabolite in all the experiments. The ethanol yield in
      anaerobic cultivations was between 0.35 and 0.48 g/g sugars consumed, depending
      on the carbon source and the growth morphology, while a yield of as low as 0.16
      g/g was obtained during aerobic cultivation. The yeast-like form of the fungus
      showed faster ethanol production with an average productivity of 0.90 g/l h from
      glucose, fructose and inverted sucrose, than the filamentous form with an average
      productivity of 0.33 g/l h. The biomass of the fungus was also analyzed with
      respect to alkali-insoluble material (AIM), chitin, and chitosan. The biomass of
      the fungus contained per g maximum 0.217 g AIM and 0.042 g chitosan in yeast-like
      cultivation under aerobic conditions.

PMID- 18712552
TI  - Antimicrobial effect of oxidized cellulose salts.
AB  - Antimicrobial properties of oxidized cellulose and its salts in linters (-L) and
      microsphere (-M) form (OKCEL H-L, OKCEL Zn-M, OKCEL ZnNa-L, OKCEL ZnNa-M and
      OKCEL Ag-L) were tested by a dilution method against a spectrum of microbial
      strains: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis,
      Bacillus licheniformis, Aspergillus niger, Penicillium chrysogenum, Rhizopus
      oryzae, Scopulariopsis brevicaulis, Candida albicans and Candida tropicalis.
      OKCEL Ag-L exhibited antimicrobial activity in the range 0.1-3.5% w/v against all
      the bacteria and fungi involved in this study. Strong inhibition by OKCEL ZnNa-M
      was observed for Staphylococcus epidermidis, Bacillus licheniformis, Rhizopus
      oryzae, Candida albicans and Candida tropicalis in the range 0.5-2.0% w/v.
      Antimicrobial effects of oxidized cellulose and its salts in textile form were
      investigated by a diffusion and dilution method against the spectrum of above
      cited microbial strains extended by Clostridium perfringens. Generally, OKCEL Ag
      T, OKCEL Zn-T and OKCEL H-T showed high antimicrobial activity against
      populations of Pseudomonas aeruginosa, Bacillus licheniformis and Staphylococcus
      epidermidis. OKCEL Zn-T was the only sample suppressing the growth of species.

PMID- 18712553
TI  - The reduction of wax precipitation in waxy crude oils by Pseudomonas species.
AB  - Crude oil with different concentrations was subjected to Pseudomonas species at
      37 degrees C and various incubation periods. The results showed that Pseudomonas
      species grew faster at 1% (v/v) concentration of crude oil and exhibited high
      biodegradation ability within 1 week. On measuring the emulsification activity
      and emulsion stability during different stages of growth, in various immiscible
      hydrocarbons, it appeared that the species was able to produce a stable emulsion
      with a maximum at the end of stationary phase of growth. The gas chromatography
      analysis of the saturated hydrocarbons of crude oil showed that, an increase in
      concentration of iso-alkanes in the range of C15-C20, and a bioconversion of
      heavy iso-alkanes in the range of C21-C22+. Chemical analysis of crude oil by
      liquid chromatographic technique before and after growth showed that, the
      saturated alkanes were more degradable than aromatic and asphaltenic compounds.
      Treatment by Pseudomonas species may possibly be an effective method for the
      biodegradation of heavy paraffinic hydrocarbon leading to an enhancement in crude
      oil properties.

PMID- 18712554
TI  - In situ separation of lactic acid from fermentation broth using ion exchange
      resins.
AB  - Lactic acid fermentation is an end product inhibited reaction. In situ separation
      of lactic acid from fermentation broth using ion exchange resins was investigated
      and compared with conventional fermentation system. Amberlite resin (IRA-400, Cl
      ) was used to separate lactic acid from fermentation broth and pH was controlled
      online with an automatic pH controller. The effect of process variables on lactic
      acid production by Lactobacillus casei in whey permeate was studied. The maximum
      productivity was obtained at pH=6.1, T=37 degrees C and impeller speed=200 rpm.
      The maximum concentration of lactic acid at optimum condition was found to be
      37.4 g/L after 38 h of fermentation using in situ separation system. The
      productivity of in situ separation system was five times increased in comparison
      with conventional system.

PMID- 18712555
TI  - Use of order-specific primers to investigate the methanogenic diversity in
      acetate enrichment system.
AB  - The applicability of order-specific primers in minimizing the possible
      underestimation of microbial diversity was evaluated via denaturing gradient gel
      electrophoresis (DGGE) analysis of a lab-scale anaerobic digester. Initially, a
      population analysis with real-time quantitative PCR demonstrated the existence of
      three methanogenic orders--Methanobacteriales, Methanomicrobiales, and
      Methanosarcinales--throughout the reaction period. DGGE analyses with three pairs
      of order-specific primers yielded eight operational taxonomic units (OTUs),
      whereas DGGE analysis with two independent Archaea-specific primers identified
      only five. Moreover, the order-specific primers amplified at least one OTU
      affiliated with each order, whereas no members of Methanobacteriales or
      Methanomicrobiales were identified with Archaea-specific primers in most samples.
      These findings provide evidence that order-specific analysis can detect the
      diversity of methanogens in greater detail than conventional Archaea-specific
      analysis.

PMID- 18712556
TI  - Use of quantitative real-time PCR to monitor population dynamics of ammonia
      oxidizing bacteria in batch process.
AB  - A quantitative real-time PCR (QPCR) assay with the TaqMan system was used to
      quantify 16S rRNA genes of beta-proteobacterial ammonia-oxidizing bacteria (AOB)
      in a batch nitrification bioreactor. Five different sets of primers, together
      with a TaqMan probe, were used to quantify the 16S rRNA genes of beta
      proteobacterial AOB belonging to the Nitrosomonas europaea, Nitrosococcus
      mobilis, Nitrosomonas nitrosa, and Nitrosomonas cryotolerans clusters, and the
      genus Nitrosospira. We also used PCR followed by denaturing gradient gel
      electrophoresis (DGGE), cloning, and sequencing of their 16S rRNA genes to
      identify the AOB species. Seed sludge from an industrial wastewater treatment
      process controlling high-strength nitrogen wastewater (500 mg/L NH4+-N) was used
      as the inoculum for subsequent batch experiment. The Nitrosomonas nitrosa cluster
      was the predominant AOB (2.3x10(5) copies/mL) in the start-up period of the batch
      experiment. However, from the exponential growth period, the Nitrosomonas
      europaea cluster was the most abundant AOB, and its 16S rRNA gene copy number
      increased to 8.9x10(6) copies/mL. The competitive dominance between the two AOB
      clusters is consistent with observed differences in ammonia tolerance and
      substrate affinity. Analysis of the DGGE results indicated the presence of
      Nitrosomonas europaea ATCC19718 and Nitrosomonas nitrosa Nm90, consistent with
      the QPCR results.

PMID- 18712557
TI  - Simultaneous effect of temperature, cyanide and ammonia-oxidizing bacteria
      concentrations on ammonia oxidation.
AB  - For biological nitrification, a set of experiments were carried out to
      approximate the response of lag period along with ammonia oxidation rate with
      respect to different concentrations of cyanide (CN-) and ammonia-oxidizing
      bacteria (AOB), and temperature variation in laboratory-scale batch reactors. The
      effects of simultaneous changes in these three factors on ammonia oxidation were
      quantitatively estimated and modeled using response surface analysis. The lag
      period and the ammonia oxidation rate responded differently to changes in the
      three factors. The lag period and the ammonia oxidation rate were significantly
      affected by the CN- and AOB concentrations, while temperature changes only
      affected the ammonia oxidation rate. The increase of AOB concentration and
      temperature alleviated the inhibition effect of cyanide on ammonia oxidation. The
      statistical method used in this study can be extended to estimate the
      quantitative effects of other environmental factors that can change
      simultaneously.

PMID- 18712558
TI  - Evaluation of the white-rot fungi Ganoderma australe and Ceriporiopsis
      subvermispora in biotechnological applications.
AB  - Ganoderma australe is a white-rot fungus that causes a selective wood
      biodelignification in some hardwoods found in the Chilean rainforest.
      Ceriporiopsis subvermispora is also a lignin-degrading fungus used in several
      biopulping studies. The enzymatic system responsible for lignin degradation in
      wood can also be used to degrade recalcitrant organic pollutants in liquid
      effluents. In this work, two strains of G. australe and one strain of C.
      subvermipora were comparatively evaluated in the biodegradation of ABTS and the
      dye Poly R-478 in liquid medium, and in the pretreatment of Eucalyptus globulus
      wood chips for further kraft biopulping. Laccase was detected in liquid and wood
      cultures with G. australe. Ceriporiopsis subvermispora produce laccase and
      manganese peroxidase when grown in liquid medium and only manganese peroxidase
      was detected during wood decay. ABTS was totally depleted by all strains after 8
      days of incubation while Poly R-478 was degraded up to 40% with G. australe
      strains and up to 62% by C. subvermispora after 22 days of incubation. Eucalyptus
      globulus wood chips decayed for 15 days presented 1-6% of lignin loss and less
      than 2% of glucan loss. Kraft pulps with kappa number 15 were produced from
      biotreated wood chips with 2% less active alkali, with up to 3% increase in pulp
      yield and up to 20% less hexenuronic acids than pulps from undecayed control.
      Results showed that G. australe strains evaluated were not as efficient as C.
      subvermispora for dye and wood biodegradation, but could be used as a feasible
      alternative in biotechnological processes such as bioremediation and biopulping.

PMID- 18712559
TI  - Decolorization of synthetic melanoidins-containing wastewater by a bacterial
      consortium.
AB  - The presence of melanoidins in molasses wastewater leads to water pollution both
      due to its dark brown color and its COD contents. In this study, a bacterial
      consortium isolated from waterfall sediment was tested for its decolorization.
      The identification of culturable bacteria by 16S rDNA based approach showed that
      the consortium composed of Klebsiella oxytoca, Serratia mercescens, Citrobacter
      sp. and unknown bacterium. In the context of academic study, prevention on the
      difficulties of providing effluent as well as its variations in compositions,
      several synthetic media prepared with respect to color and COD contents based on
      analysis of molasses wastewater, i.e., Viandox sauce (13.5% v/v), caramel (30%
      w/v), beet molasses wastewater (41.5% v/v) and sugarcane molasses wastewater (20%
      v/v) were used for decolorization using consortium with color removal 9.5, 1.13,
      8.02 and 17.5%, respectively, within 2 days. However, Viandox sauce was retained
      for further study. The effect of initial pH and Viandox concentration on
      decolorization and growth of bacterial consortium were further determined. The
      highest decolorization of 18.3% was achieved at pH 4 after 2 day of incubation.
      Experiments on fresh or used medium and used or fresh bacterial cells, led to
      conclusion that the limitation of decolorization was due to nutritional
      deficiency. The effect of aeration on decolorization was also carried out in 2 L
      laboratory-scale suspended cell bioreactor. The maximum decolorization was 19.3%
      with aeration at KLa=2.5836 h(-1) (0.1 vvm).

PMID- 18712560
TI  - Growth of Trametes versicolor on phenol.
AB  - Trametes versicolor 1 was shown to grow on phenol as its sole carbon and energy
      source. The culture growth and degradation ability dependence on culture medium
      pH value was observed. The optimal pH value of a liquid Czapek salt medium was
      6.5. The investigated strain utilized completely 0.5 g/l phenol in 6 days. The
      dynamics of the phenol degradation process was investigated. The process was
      characterized by specific growth rate micromax 0.33 h(-1), metabolic coefficient
      k=4.4, yield coefficient Yx/s=0.23 and rate of degradation Q=0.506 h(-1). The
      intracellular activities of phenol hydroxylase (0.333 U/mg protein) and cis,cis
      muconate lactonizing enzyme (0.41 U/mg protein) were demonstrated for the first
      time in this fungus. In an attempt to estimate the occurrence of gene sequences
      in T. versicolor 1 related to phenol degradation pathway a dot blot analysis with
      total DNA isolated from this strain was performed. Two synthetic oligonucleotides
      were used as hybridizing probes. One of the probes was homologous to the 5'end of
      phyA gene coding for phenol hydroxylase in Trichosporon cutaneum ATCC 46490. The
      other probe was created on the basis of cis,cis-muconate lactonizing enzyme
      coding gene in T. cutaneum ATCC 58094. The results of these investigations showed
      that T. versicolor 1 may carry genes similar to those of Trichosporon cutaneum
      capable to degrade phenol.

PMID- 18712561
TI  - Biosurfactant production by free and alginate entrapped cells of Pseudomonas
      fluorescens.
AB  - Production of biosurfactant by free and alginate-entrapped cells of Pseudomonas
      fluorescens Migula 1895-DSMZ was investigated using olive oil as the sole carbon
      and energy source. Biosurfactant synthesis was followed by measuring surface
      tension and emulsifying index E24 over 5 days at ambient temperature and at
      neutral pH. Diffusional limitations in alginate beads affected the kinetics of
      biosurfactant production when compared to that obtained with free cells culture.
      Nevertheless, the emulsion stability was improved and fewer by-products
      interfered with the biosurfactant activity. A decrease in pH down to 5 in the
      case of immobilized cells was observed during the first 3 days, after which it
      returned to its initial value. The minimum values of surface tension were 30 and
      35 dynes cm(-1) achieved after 40 and 72 h with free and immobilized cells,
      respectively, while the corresponding maximum E24 values were 67 and 62%,
      respectively. After separation by acetone precipitation, the biosurfactant showed
      a rhamnolipid-type in nature, and had a good foaming and emulsifying activities.
      The critical micellar concentration was found to be 290 mg l(-1). The
      biosurfactant also showed good stability during exposure to high temperatures (up
      to 120 degrees C for 15 min), to high salinity (10% NaCl) and to a wide range of
      pH (4-9).

PMID- 18712562
TI  - Phenol and cresol mixture degradation by the yeast Trichosporon cutaneum.
AB  - Most industrial wastes contain different organic mixtures, making important the
      investigation on the microbial destruction of composite substrates. The
      capability of microbes to remove harmful chemicals from polluted environments
      strongly depends on the presence of other carbon and energy substrates. The
      effect of mixtures of phenol- and methyl-substituted phenols (o-, m-, p-cresol)
      on the growth behaviour and degradation capacity of Trichosporon cutaneum strain
      was investigated. The cell-free supernatants were analysed by HPLC. It was
      established that the presence of o-, m- and p- cresol has not prevented complete
      phenol assimilation but had significant delaying effect on the phenol degradation
      dynamics. The mutual influence of phenol and p-cresol was investigated. We
      developed the kinetic model on the basis of Haldane kinetics, which used model
      parameters from single-substrate experiments to predict the outcome of the two
      substrate mixture experiment. The interaction coefficients indicating the degree
      to which phenol affects the biodegradation of p-cresol and vice versa were
      estimated. Quantitative estimation of interaction parameters is essential to
      facilitate the application of single or mixed cultures to the bio-treatment of
      hazardous compounds.

PMID- 18712563
TI  - Elective resection for diverticular disease: an evidence-based review.
AB  - Controversy exists as to the most appropriate management of patients following
      two episodes of diverticulitis. Despite a growing body of new evidence
      challenging the concept of elective sigmoid resection after a patient experiences
      two attacks of diverticulitis, we continue to base our practice on outdated
      studies carried out more than 30 years ago. The recommendation that patients
      undergo elective sigmoid resection after two attacks of acute diverticulitis
      should be re-evaluated as it is generally inappropriate and is not cost
      effective. Elective resection for uncomplicated diverticulitis does not alter
      outcome, nor does it decrease mortality or prevent complications of the disease.
      In fact, based on current literature, 18 patients would have to undergo elective
      operation to prevent one emergency surgery. This article aims to review the
      current evidence for elective resection following episodes of diverticular
      disease and addresses emerging controversies in the management of this disease.

PMID- 18712564
TI  - Pharmacologic effects of grain weevil extract on isolated guinea pig tracheal
      smooth muscle.
AB  - The grain weevil, an insect (pest) that infects grain, is a frequent contaminant
      of processed wheat, and its presence may contribute to respiratory abnormalities
      in grain workers. We studied the in vitro effects of an extract of grain weevil
      (GWE) on airway smooth muscle. Pharmacologic studies included in vitro challenge
      of guinea pig trachea with GWE, in parallel organ baths, pretreated with mediator
      modifying agents or a control solution. Dose-related contractions of
      nonsensitized guinea pig trachea (GPT) were demonstrated using this extract.
      Pharmacologic studies were performed by pretreating guinea pig tracheal tissue
      with drugs known to modulate smooth muscle contraction: atropine, indomethacin,
      pyrilamine, acivicin, NDGA, BPB, TMB8, captopril, and capsaicin. Atropine,
      pyrilamine, BPB, and capsaicin significantly reduced the contractile effects of
      the extract at most of the challenge doses (p < 0.01 or p < 0.05). Inhibition of
      GWE-induced contraction by blocking of other mediators was less complete. We
      suggest that GWE causes dose-related airway smooth muscle constriction of the GPT
      by nonimmunologic mechanisms involving a variety of airway mediators and possibly
      cholinergic receptors.

PMID- 18712565
TI  - Thraustochytrid Marine Protists: production of PUFAs and Other Emerging
      Technologies.
AB  - Thraustochytrids, the heterotrophic, marine, straminipilan protists, are now
      established candidates for commercial production of the omega-3 polyunsaturated
      fatty acid (omega-3 PUFA), docosahexaenoic acid (DHA), that is important in human
      health and aquaculture. Extensive screening of cultures from a variety of
      habitats has yielded strains that produce at least 50% of their biomass as
      lipids, and DHA comprising at least 25% of the total fatty acids, with a yield of
      at least 5 g L(-1). Most of the lipids occur as triacylglycerols and a lesser
      amount as phospholipids. Numerous studies have been carried out on salinity, pH,
      temperature, and media optimization for DHA production. Commercial production is
      based on a fed batch method, using high C/N ratio that favors lipid accumulation.
      Schizochytrium DHA is now commercially available as nutritional supplements for
      adults and as feeds to enhance DHA levels in larvae of aquaculture animals.
      Thraustochytrids are emerging as a potential source of other PUFAs such as
      arachidonic acid and oils with a suite of PUFA profiles that can have specific
      uses. They are potential sources of asataxanthin and carotenoid pigments, as well
      as other lipids. Genes of the conventional fatty acid synthesis and the
      polyketide-like PUFA synthesis pathways of thraustochytrids are attracting
      attention for production of recombinant PUFA-containing plant oils. Future
      studies on the basic biology of these organisms, including biodiversity,
      environmental adaptations, and genome research are likely to point out directions
      for biotechnology explorations. Potential areas include enzymes, polysaccharides,
      and secondary metabolites.

PMID- 18712566
TI  - Residual inhibition functions overlap tinnitus spectra and the region of auditory
      threshold shift.
AB  - Animals exposed to noise trauma show augmented synchronous neural activity in
      tonotopically reorganized primary auditory cortex consequent on hearing loss.
      Diminished intracortical inhibition in the reorganized region appears to enable
      synchronous network activity that develops when deafferented neurons begin to
      respond to input via their lateral connections. In humans with tinnitus
      accompanied by hearing loss, this process may generate a phantom sound that is
      perceived in accordance with the location of the affected neurons in the cortical
      place map. The neural synchrony hypothesis predicts that tinnitus spectra, and
      heretofore unmeasured "residual inhibition functions" that relate residual
      tinnitus suppression to the center frequency of masking sounds, should cover the
      region of hearing loss in the audiogram. We confirmed these predictions in two
      independent cohorts totaling 90 tinnitus subjects, using computer-based tools
      designed to assess the psychoacoustic properties of tinnitus. Tinnitus spectra
      and residual inhibition functions for depth and duration increased with the
      amount of threshold shift over the region of hearing impairment. Residual
      inhibition depth was shallower when the masking sounds that were used to induce
      residual inhibition showed decreased correspondence with the frequency spectrum
      and bandwidth of the tinnitus. These findings suggest that tinnitus and its
      suppression in residual inhibition depend on processes that span the region of
      hearing impairment and not on mechanisms that enhance cortical representations
      for sound frequencies at the audiometric edge. Hearing thresholds measured in age
      matched control subjects without tinnitus implicated hearing loss as a factor in
      tinnitus, although elevated thresholds alone were not sufficient to cause
      tinnitus.

PMID- 18712567
TI  - Development of an automatic classification system for differentiation of
      obstructive lung disease using HRCT.
AB  - The motivation is to introduce new shape features and optimize the classifier to
      improve performance of differentiating obstructive lung diseases, based on high
      resolution computerized tomography (HRCT) images. Two hundred sixty-five HRCT
      images from 82 subjects were selected. On each image, two experienced
      radiologists selected regions of interest (ROIs) representing area of severe
      centrilobular emphysema, mild centrilobular emphysema, bronchiolitis obliterans,
      or normal lung. Besides 13 textural features, additional 11 shape features were
      employed to evaluate the contribution of shape features. To optimize the system,
      various ROI size (16 x 16, 32 x 32, and 64 x 64 pixels) and other classifier
      parameters were tested. For automated classification, the Bayesian classifier and
      support vector machine (SVM) were implemented. To assess cross-validation of the
      system, a five-folding method was used. In the comparison of methods employing
      only the textural features, adding shape features yielded the significant
      improvement of overall sensitivity (7.3%, 6.1%, and 4.1% in the Bayesian and
      9.1%, 7.5%, and 6.4% in the SVM, in the ROI size 16 x 16, 32 x 32, 64 x 64
      pixels, respectively; t test, P < 0.01). After feature selection, most of cluster
      shape features were survived ,and the feature selected set shows better
      performance of the overall sensitivity (93.5 +/- 1.0% in the SVM in the ROI size
      64 x 64 pixels; t test, P < 0.01). Adding shape features to conventional texture
      features is much useful to improve classification performance of obstructive lung
      diseases in both Bayesian and SVM classifiers. In addition, the shape features
      contribute more to overall sensitivity in smaller ROI.

PMID- 18712568
TI  - Prognostic relevance of lymph node ratio and number of resected nodes after
      curative resection of ampulla of Vater carcinoma.
AB  - BACKGROUND: Nodal metastasis is considered a major prognostic factor in patients
      with ampulla of Vater carcinoma (AVC). No study has investigated the significance
      of the ratio between metastatic and resected/examined lymph nodes (LNR) in
      patients with AVC. METHODS: Demographic, operative, and pathology data, including
      number of resected/evaluated nodes and LNR, were collected from patients who
      underwent pancreaticoduodenectomy with radical intent for invasive AVC from 1990
      to 2005. Survival rates and recurrence patterns were evaluated and predictors
      were identified. RESULTS: In 90 evaluable patients (51 males, 39 females, median
      age 62.5 years), 5-year disease-specific survival (DSS) was 61%. The median
      number of resected/evaluated nodes was 16 (range: 5-47); 50% of the patients had
      nodal metastases. The 5-year DSS according to LNR was 75%, 49%, 38%, and 0% for
      LNR = 0, LNR >0 and < or =0.2, LNR >0.2, and < or =0.4, and LNR >0.4 (P = 0.002),
      respectively. The 5-year DSS was 81% in patients with >16 resected/evaluated
      nodes compared with 45% in those with < or =16 resected/evaluated nodes (P =
      0.001). On multivariate analysis LNR and a number of resected/evaluated nodes >16
      were significant predictors of survival; a number of resected/evaluated nodes >16
      was also the only independent predictor of recurrence. CONCLUSIONS: After
      curative resection for AVC, LNR and a cutoff of 16 resected/evaluated nodes are
      powerful prognostic factors. LNR might represent a major parameter for patient
      stratification in adjuvant treatment trials.

PMID- 18712569
TI  - Association of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation
      with p53 mutation occurrence in non-small cell lung cancer with different
      histology, gender, and smoking status.
AB  - BACKGROUND: O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation
      has been demonstrated to associate with the G:C-->A:T transition mutation in the
      p53 gene of lung tumors. The purpose of this study is to clarify whether MGMT
      promoter methylation is not only associated with the shift from the G:C-->A:T
      mutation in the p53 gene but also whether MGMT increases other mutation patterns
      in lung tumors. MATERIALS AND METHODS: To further verify whether a different
      prevalence of MGMT promoter methylation is observed in lung tumors with a
      different tumor histology, gender, and smoking status, 220 lung tumors were
      collected to evaluate the status of MGMT promoter methylation and p53 mutation
      using methylation-specific PCR (MSP) and direct sequencing, respectively.
      RESULTS: The data shows that a higher prevalence of MGMT promoter methylation was
      observed in tumors with the G:C-->A:T transition or other p53 mutation patterns
      compared with those with p53 wild-type (P < 0.001 for G:C-->A:T; P = 0.015 for
      other mutation patterns), and this prevalence was more pronounced in tumors from
      male than from female patients. MGMT promoter methylation in p53 mutation
      patterns had a different effect on squamous cell carcinomas (SCC) and
      adenocarcinomas (ADC). Interestingly, the highest prevalence of MGMT promoter
      methylation was found in male nonsmokers followed by male smokers and female
      nonsmokers. This may be a partial explanation for the reason why male nonsmokers
      had a higher p53 mutation occurrence than female nonsmokers. CONCLUSIONS: MGMT
      promoter methylation may associate with increased occurrence of p53 mutation
      including the G:C-->A:T transition and other p53 mutation patterns in lung
      cancer, especially among male nonsmokers.

PMID- 18712571
TI  - Optimal dynamic allocation of conservation funding among priority regions.
AB  - The optimal allocation of conservation resources between biodiverse conservation
      regions has generally been calculated using stochastic dynamic programming, or
      using myopic heuristics. These solutions are hard to interpret and may not be
      optimal. To overcome these two limitations, this paper approaches the optimal
      conservation resource allocation problem using optimal control theory. A solution
      using Pontryagin's maximum principle provides novel insight into the general
      properties of efficient conservation resource allocation strategies, and allows
      more extensive testing of the performance of myopic heuristics. We confirmed that
      a proposed heuristic (minimize short-term loss) yields near-optimal results in
      complex allocation situations, and found that a qualitative allocation feature
      observed in previous analyses (bang-bang allocation) is a general property of the
      optimal allocation strategy.

PMID- 18712570
TI  - Annexin II overexpression predicts rapid recurrence after surgery in pancreatic
      cancer patients undergoing gemcitabine-adjuvant chemotherapy.
AB  - BACKGROUND: Gemcitabine has been shown to exhibit significant clinical activity
      against pancreatic cancer and has become a first-line chemotherapeutic for this
      disease in recent years. However, there are still many patients who do not
      respond to this treatment and it is expected to improve the clinical outcome if
      we can develop a method to predict the efficacy of gemcitabine before treatment.
      The purpose of this study was to determine novel factors that make pancreatic
      cancer resistant to gemcitabine. MATERIALS AND METHODS: Using the high-resolution
      proteomic approach, agarose two-dimensional gel electrophoresis, we compared
      protein profiling of a gemcitabine-resistant pancreatic cancer cell line with its
      wild-type. RESULTS: We identified Annexin II as an up-regulated protein in the
      gemcitabine-resistant pancreatic cancer cell line. Immunohistochemistry
      demonstrated that Annexin II was mainly expressed at the cell surface of
      pancreatic cancer cells. Interestingly, Annexin II overexpression in cancer cells
      was significantly associated with rapid recurrence after gemcitabine adjuvant
      chemotherapy in postoperative patients (P = .0078), and its staining was also an
      independent prognostic indicator of recurrence in pancreatic cancer patients who
      underwent adjuvant gemcitabine treatment after curative surgery on multivariate
      analysis (P = .0047). In addition, inhibition of Annexin II expression by siRNA
      in pancreatic cancer cell lines increased the cytotoxic efficacy of gemcitabine.
      These results indicate that Annexin II overexpression may induce gemcitabine
      resistance in pancreatic cancer resulting in rapid recurrence. CONCLUSIONS:
      Analysis of Annexin II expression in cancer tissues may predict the clinical
      outcome of gemcitabine treatment, leading to the development of a new method for
      tailor-made treatment for this disease.

PMID- 18712572
TI  - Quality of life and symptomatic response to gastric neurostimulation for
      gastroparesis.
AB  - BACKGROUND: Gastroparesis can be a difficult problem with patients suffering from
      nausea, vomiting, bloating, and pain intractable to medical management. Gastric
      neurostimulation has been developed as an adjunctive treatment for patients with
      diabetic and idiopathic gastroparesis unresponsive to pharmacologic and dietary
      treatment. The purpose of this study is to report symptomatic and quality-of-life
      response to gastric neurostimulation. METHODS: This study was approved by the
      institutional review board, and patients had informed consent. The gastric
      neurostimulation device (Enterra therapy, Medtronic, Inc., Minneapolis, MN, USA)
      is approved by the Food and Drug Administration under the Humanitarian Device
      Exemption. Candidates for placement were patients with either idiopathic or
      diabetic gastroparesis who had symptomatic failure to dietary changes and to
      prokinetic and antiemetic drugs. Before placement, the patients' symptoms were
      recorded, and patients completed the Gastrointestinal Symptom Rating Scale (GSRS,
      three domains: dyspeptic syndrome, indigestion syndrome, and bowel dysfunction
      syndrome) and the Short Form-36 (SF-36, eight domains: physical functioning, role
      physical, role-emotional, bodily pain, vitality, mental health, social
      functioning, general health, plus a health transition item). The device was
      surgically placed using a hybrid laparoscopic/open technique. Patients were
      followed and adjustments made on the device until satisfactory symptom control
      was achieved. At that time, patients completed both the GSRS and SF-36, and
      comparisons were made to preoperative values. RESULTS: Forty-two patients had the
      device placed, 29 women, aged 41 (SD +14) years, 24 diabetic patients, 17
      idiopathic patients, one postgastrectomy patient. Median follow-up was 12 months
      (range 1-42 months). There was a 2% immediate postoperative morbidity rate and 7%
      long-term morbidity rate (device extrusion). Thirty-one patients (74%) responded
      to gastric neurostimulation of variable degrees. Eleven patients had no response
      or had worsening symptoms. Of the patients who responded, there were
      statistically significant improvements in all three domains of the GSRS. Median
      scores (with interquartile ranges): dyspeptic syndrome, 9 (7-11.5) to 4 (2.5-6),
      p = 0.02; indigestion syndrome, 5 (2-7) to 4 (0-5), p = 0.05; bowel dysfunction
      syndrome, 3 (2-3) to 1 (0-1), p = 0.01. In the SF-36, there were statistically
      significant improvement in the health transition item, 4 (4-5) to 1.5 (1-3), p =
      0.01; and social functioning domain, 25 (12.5-62.5) to 75 (50-87.5), p = 0.03.
      CONCLUSIONS: Three quarters of gastroparesis patients responded to gastric
      neurostimulation to variable degrees. Gastrointestinal-specific symptoms are
      improved in responders. Patients felt that there health and social functioning
      (SF) improved, although there was no significant difference in the other domains.
      These results are encouraging considering that these patients had intractable
      symptoms with no other effective treatments available.

PMID- 18712573
TI  - Recurrent symptoms after fundoplication with a negative pH study--recurrent
      reflux or functional heartburn?
AB  - INTRODUCTION: A small cohort of patients present after antireflux surgery
      complaining of recurrent heartburn. Over two thirds of these patients will have a
      negative 24-h pH study. The aim of our study is to determine whether these
      patients have an associated functional disorder or abnormal cytokine activity and
      to examine the reproducibility of pH testing. METHODS: A prospective analysis was
      carried out on a cohort of patients who had undergone a fundoplication and
      postoperative pH testing for recurrent heartburn: group A--patients with
      recurrent heartburn and a negative 24-h pH study and group B (control group)-
      patients with recurrent heartburn and a positive pH study. Questionnaires, a
      blood sample, and repeat pH testing were completed. RESULTS: Sixty-nine patients
      were identified. Group A's depression score (8.6 +/- 4.1) was significantly
      higher than group B's (5.9 +/- 4.2; P = 0.03). Cytokine levels were similar in
      both groups. Forty-seven of 49 (96%) patients who underwent repeat pH testing had
      a negative study. Symptom-reflux correlation was highly significant (P < 0.001).
      CONCLUSION: Some patients with recurrent heartburn and a negative pH study have
      associated functional or psychiatric comorbidities such as depression.
      Reproducibility of 24-h pH testing in these patients is excellent.

PMID- 18712574
TI  - Assessment of the application of the intragastric balloon together with
      sibutramine: a prospective clinical study.
AB  - BACKGROUND: The aim of this study is the prospective evaluation of the results of
      Bioenterics intragastric balloon (BIB) with sibutramine and BIB placement alone
      in the treatment of obesity. METHODS: The patients evaluated between March 2006
      and January 2007 and enrolled in this study were assessed in two groups as group
      A (BIB + sibutramine) and group B (BIB). After the follow-up of the patients for
      6 months, body mass index (BMI), weight loss, excess weight loss (EWL%), and
      excess body mass index loss (EBMIL%) values of the patients in both groups were
      compared. RESULTS: According to the comparison of the weights of the patients in
      groups A and B at 6 months with the beginning weights of the patients in both
      groups, there was statistically significant weight loss (p < 0.01). The total
      weight loss at 6 months in group A was statistically significantly higher than
      that in group B (p < 0.05). The patients in group A had a mean BMI 34.53 +/- 6.63
      kg/m(2), EWL% 38.77 +/- 11.88%, EBMIL% 49.93 +/- 21.52% after 6 months; the
      patients in group B had a mean BMI 35.29 +/- 6.36 kg/m(2), EWL% 29.06 +/- 17.82%,
      EBMIL% 36.51 +/- 23.69% after 6 months. There was no statistically significant
      difference between group A and group B according to the BMI, EWL%, and EBMIL%
      values (p > 0.05). CONCLUSION: In the management of obesity, using BIB together
      with sibutramine before the treatment in the patient group who are planned to
      have surgery, compared with using only BIB, provides more effective weight loss.

PMID- 18712575
TI  - A prospective randomized study comparing patients with morbid obesity submitted
      to laparotomic gastric bypass with or without omentectomy.
AB  - BACKGROUND: Visceral fat, especially the greater omentum, seems to be an
      important factor in the development of some metabolic disturbances such as
      insulin resistance, hyperglycemia, and dyslipidemia. Therefore, we wanted to
      evaluate the influence of resecting or leaving in situ the greater omentum in a
      group of patients with morbid obesity. METHODS: Seventy patients with morbid
      obesity were submitted to laparotomic resectional gastric bypass and an
      omentectomy was randomly performed in some patients. Body mass index (BMI), serum
      levels of sugar, insulin, total cholesterol, and triglycerides were determined
      prior to surgery and followed up on for 2 years afterwards. RESULTS: Two years
      after surgery, no differences were seen in BMI levels in either group. Blood
      sugar levels, serum insulin, total cholesterol levels, and serum triglycerides
      had similar values in both groups. Arterial hypertension had similar behavior.
      CONCLUSIONS: Based on these results, omentectomy is not justified as part of
      bariatric surgery. Its theoretical advantages are not reflected in this
      prospective random trial.

PMID- 18712576
TI  - What is in a name? Understanding the implications of participant terminology.
AB  - The authors discuss the history of research terminology in American psychology
      with respect to the various labels given to those upon whom we conduct research
      ("observer"-"subject"-"participant"-"client"). This history is supplemented with
      an analysis of participant terminology in APA manuals from four historical eras,
      from the 1950s to the present. The general trend in participant terminology
      reflects the overall trends in American psychology, beginning with a complex
      lexicon that admitted both the passive and the active research participant,
      followed by a dominance of the passive term 'subject' and ending with the
      terminological ambiguity and multiplicity reflected in contemporary psychology.
      This selective history serves to contextualize a discussion of the meaning,
      functions, and implications of the transformations in, and debates over,
      participant terminology.

PMID- 18712577
TI  - The monkey as a psychological subject.
AB  - Many species in long-term captivity have tried to kill time by playing friendly
      games with their warders. In the end, only rhesus monkeys (Macaca mulatta) could
      tolerate the tedious hide-and-seek games that their human jailers prefer to play.
      In this article, written many years before the Stockholm syndrome was first
      described, the author relates how it was eventually discovered which species is
      most willing to contribute to the development of a genuinely scientific human
      psychology.

PMID- 18712578
TI  - Papers presented at the Annual Meetings of the Knee Society: editorial comment.

PMID- 18712579
TI  - TKA sagittal alignment with navigation systems and conventional techniques vary
      only a few degrees.
AB  - Navigation systems have been developed to achieve more reliable prosthetic
      alignment in TKAs. However, the component alignment in the sagittal plane is
      reportedly less reliable than in the coronal plane even with navigation systems.
      We measured and compared sagittal prosthetic alignments for TKAs with the
      conventional technique and three navigation approaches to establish reference
      frames, using radiographs of the entire lower extremity while standing. The
      sagittal alignments simulated on the radiographs with the conventional technique
      and navigation systems differed by a mean of 2 degrees to 4 degrees . Use of
      navigation systems resulted in a mean of 1 degrees to 4 degrees hyperextension
      between the femoral and tibial components and use of the conventional technique
      resulted in a mean of 1 degrees flexion. Use of different reference points on the
      distal femoral condyle for the navigation systems resulted in differences of as
      much as 3 degrees alignment in the sagittal plane. Although optimal prosthetic
      alignment for TKA in the sagittal plane is unknown, surgeons and technicians
      using navigation systems should be aware of this difference in the sagittal plane
      and the risk of hyperextension between the femoral and tibial components, which
      might be associated with osteolysis and anterior post-cam impingement.

PMID- 18712580
TI  - The condylar cutoff sign: quantifying lateral femoral condylar hypoplasia in a
      complete discoid meniscus.
AB  - We describe the condylar cutoff sign, a radiographic sign in knees with a discoid
      lateral meniscus, for diagnosis of complete discoid meniscus. We retrospectively
      reviewed tunnel-view radiographs of 100 patients (100) knees including 50 with
      complete discoid lateral meniscus and 50 with normal menisci. All patients were
      18 years of age or older. All of the knees were arthroscopically examined. We
      developed a method to measure the prominence of the femoral condyle adjacent to
      the intercondylar notch on a tunnel view of the knee. The prominence ratio, the
      ratio of the medial and lateral condylar prominence, was compared and analyzed.
      The measurements were performed by three observers on two separate occasions to
      determine reliability. The intraobserver and interobserver variability study
      revealed high reliability with correlation coefficients ranging from 0.86 to
      0.99. Using a cutoff ratio of 0.8, we observed a major difference between the two
      groups and found the ratio had 76% sensitivity, 96% specificity, 95% positive
      predictive value, and 80% negative predictive value in every set of measurements.
      The sign has high specificity and reliability but might not apply to younger
      patients. LEVEL OF EVIDENCE: Level II, diagnostic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 18712581
TI  - Letter to the editor: Transpedicle body augmenter: a further step in treating
      burst fractures.

PMID- 18712582
TI  - Does TKA improve functional outcome and range of motion in patients with stiff
      knees?
AB  - The main goals of TKA are pain relief and improvement of function and range of
      motion (ROM). To ascertain whether TKA in patients with stiff knees would relieve
      pain and improve functional outcome and ROM, we asked four questions: whether (1)
      Knee Society and WOMAC scores would improve after TKA; (2) poor preoperative ROM
      would improve after TKA; (3) the revision rate of TKA in stiff knees would be
      high; and (4) complication rates would be high in these patients after TKA. We
      retrospectively reviewed 74 patients (86 knees) with stiff knees (mean age, 56.8
      years) who underwent TKAs with a condylar constrained or a posterior stabilized
      prosthesis. The minimum followup was 5 years (mean, 9.1 years; range, 5-12
      years). The mean preoperative Hospital for Special Surgery knee score and Knee
      Society knee and functional scores were 42, 11, and 42 points, respectively, and
      postoperatively they were 84, 90, and 84 points, respectively. Preoperative and
      postoperative total WOMAC scores were 73 and 34 points, respectively. One knee
      (1.2%) had aseptic loosening of the tibial component and 12 knees (14%) had
      complications. Despite a relatively high rate of complications, most patients had
      substantial improvement in function. LEVELS OF EVIDENCE: Level III, therapeutic
      study. See the Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 18712583
TI  - Management of the deficient patella in revision total knee arthroplasty.
AB  - There are a number of options available to manage the patella when revising a
      failed total knee arthroplasty. If the previous patellar component is well-fixed,
      undamaged, not worn, and compatible with the femoral revision component, then it
      can be retained. When a patellar component necessitates revision and is removed
      with adequate remaining patellar bone stock, an onlay-type all-polyethylene
      cemented implant can be used. Management of the patella with severe bony
      deficiency remains controversial. Treatment options for the severely deficient
      patella include the use of a cemented all-polyethylene biconvex patellar
      prosthesis, patellar bone grafting and augmentation, patellar resection
      arthroplasty (patelloplasty), performing a gull-wing osteotomy, patellectomy, or
      the use of newer technology such as a tantalum (trabecular metal) patellar
      prosthesis. Severe patellar bone deficiency is a challenging situation because
      restoration of the extensor mechanism, proper patellar tracking, and satisfactory
      anatomic relationships with the femoral and tibial components are critical for an
      optimal clinical outcome. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 18712584
TI  - Intravascular delivery of particulate systems: does geometry really matter?
AB  - In cancer therapy and imaging, the systemic passive delivery of particulate
      systems has relied on the enhanced permeability and retention (EPR) effect:
      sufficiently small particles can cross the endothelial fenestrations and
      accumulate in the tumor parenchyma. The vast majority of man-made particulates
      exhibit a spherical shape as a result of surface energy minimization during their
      synthesis. The advent of phage display libraries, which are revealing the
      extraordinary molecular diversity of endothelial cells, and the development of
      processes for fabricating particles with shapes other than spherical are opening
      the path to new design solutions for systemically administered targeted
      particulates. In this paper, the role of particle geometry (i.e., size and shape)
      is discussed at the tissue and cellular scales. Emphasis is placed on how the
      synergistic effect of particle geometry and molecular targeting can enhance the
      specificity of delivery. The intravascular delivery process has been broken into
      three events: margination, firm adhesion and control of internalization.
      Predictions from mathematical models and observations from in-vitro experiments
      were used to show the relevance of particle geometry in systemic delivery.
      Rational design of particulate systems should consider, beside the physico
      chemical properties of the surface coatings, geometrical features as size and
      shape. The integration of mathematical modeling with in-vitro and in-vivo testing
      provides the tools for establishing a rational design of nanoparticles.

PMID- 18712585
TI  - Development of a smart nano-vehicle to target cerebrovascular amyloid deposits
      and brain parenchymal plaques observed in Alzheimer's disease and cerebral
      amyloid angiopathy.
AB  - PURPOSE: To design a smart nano-vehicle (SNV) capable of permeating the blood
      brain barrier (BBB) to target cerebrovascular amyloid formed in both Alzheimer's
      disease (AD) and cerebrovascular amyloid angiopathy (CAA). METHODS: SNV consists
      of a chitosan polymeric core prepared through ionic gelation with
      tripolyphosphate. A polyamine modified F(ab') portion of IgG4.1, an anti-amyloid
      antibody, was coated as a biosensor on the SNV surface. A similar polymeric core
      coated with bovine serum albumin (BSA) served as a control nano-vehicle (CNV).
      The BBB uptake of (125)I-SNVs and (125)I-CNVs was evaluated in mice. The uptake
      and transcytosis of SNVs and CNVs across bovine brain microvascular endothelial
      cells (BBMECs) was evaluated using flow cytometry and confocal microscopy.
      RESULTS: Plasma clearance of (125)I-SNVs was nine times higher than that of the
      (125)I-CNVs. However, the uptake of (125)I-SNVs in various brain regions was
      about 8 to 11 times higher than that of (125)I-CNVs. The uptake of FITC-BSA
      loaded SNVs in BBMECs was twice the uptake of FITC-BSA loaded CNVs. Confocal
      micrographs demonstrated the uptake and transcytosis of Alexa Fluor 647 labeled
      SNVs, but not CNVs, across the BBMEC monolayer. CONCLUSIONS: SNVs are capable of
      carrying a payload of model protein across the BBB to target cerebral amyloid.

PMID- 18712586
TI  - The mouse as a model for mammary tumorigenesis: history and current aspects.

PMID- 18712587
TI  - 5' regulatory and 3' untranslated region polymorphisms of vitamin D receptor gene
      in south Indian HIV and HIV-TB patients.
AB  - INTRODUCTION: Vitamin D receptor (VDR) gene polymorphisms in the 5' regulatory
      region (Cdx2 and A-1012G), coding region (FokI), and 3' untranslated region (UTR;
      BsmI, ApaI, and TaqI) were studied to find out whether these polymorphisms are
      associated with susceptibility to or protection against HIV-1 and development of
      tuberculosis (TB) in human immunodeficiency virus (HIV)-1-infected patients.
      STUDY SUBJECTS AND METHODS: The study was carried out in 131 HIV patients without
      TB (HIV+ TB-) and 113 HIV patients with TB (HIV+ TB+; includes 82 patients with
      pulmonary TB (HIV+ PTB+) and 31 with extra pulmonary TB), 108 HIV-negative
      pulmonary TB patients (HIV- PTB+), and 146 healthy controls. RESULTS: Among the
      5' regulatory and coding region polymorphisms, significantly increased frequency
      of G/A genotype of Cdx-2 was observed in HIV+ TB- group compared to controls (p =
      0.012, odds ratio (OR) 1.89 95% confidence interval (CI) 1.14-3.15). In the 3'
      UTR genotypes, a decreased frequency of b/b genotype of BsmI in total HIV
      patients (p = 0.014, OR 0.54 95% CI 0.32-0.89) and increased frequencies of A/A
      genotype of ApaI in HIV+ TB+ patients (p = 0.041, OR 1.77 95% CI 1.02-3.06) and
      t/t genotype of TaqI in HIV+ PTB+ patients (p = 0.05, OR 2.32 95% CI 0.99-5.46)
      were observed compared to controls. Haplotype analysis revealed significantly
      increased frequencies of 3' UTR haplotype B-A-t in HIV+ TB+ and HIV+ PTB+ groups
      (Pc = 0.030, OR 1.75 95% CI 1.14-2.66) and decreased frequencies of b-A-T
      haplotype in total HIV patients (Pc = 0.012, OR 0.46 95% CI 0.27-0.77), HIV+ TB-
      (p = 0.031 OR 0.48 95% CI 0.25-0.89), and HIV+ PTB+ groups (Pc = 0.04, OR 0.47
      95% CI 0.23-0.89) compared to controls. CONCLUSIONS: The results suggest that VDR
      gene 3' UTR haplotype b-A-T may be associated with protection against HIV
      infection while B-A-t haplotype might be associated with susceptibility to
      development of TB in HIV-1-infected patients.

PMID- 18712588
TI  - Sequence analysis of the gene coding for the S1 glycoprotein of infectious
      bronchitis virus (IBV) strains from New Zealand.
AB  - Four new infectious bronchitis virus (IBV) strains (T6, K32, K43, and K87) were
      isolated from clinically infected chickens in New Zealand. These strains were
      compared with four strains (A, B, C, and D), which had circulated 25 years
      previously, by sequencing the gene coding for the S1 subunit of the spike
      glycoprotein. Analysis of the nucleotide and deduced amino acid sequences
      revealed that the eight strains from New Zealand are genetically related and
      share greater than 82.8% nucleotide and 79% amino acid homology within the S1
      region. Strains T6, K43, and K87 were more than 99% homologous to previously
      described strains C and D. A fourth new strain (K32) was most closely related to
      the previously described B strain. Phylogenetic analysis of strains revealed that
      New Zealand strains were more closely related to Australian than European or
      North American strains. The New Zealand A strain shared 99.5% nucleotide and
      98.7% amino acid homology with the Australian Vic S strain. Deduced amino acid
      sequence of the S1 glycoprotein indicated differences between strains that were,
      in general, consistent with virus neutralization patterns.

PMID- 18712590
TI  - Analysis of the biological and molecular variability of Watermelon mosaic virus
      isolates from Iran.
AB  - Watermelon mosaic virus (WMV) is one of the most important viruses that causes
      different symptoms in Cucurbitaceae. WMV is a potyvirus with a worldwide
      distribution, but occurs most commonly in temperate and Mediterranean regions.
      Cucurbit species grown in Yazd, Esfahan, West Azerbaijan, Hormozgan, and Kerman
      provinces were surveyed for the relative incidence of WMV in 2004-2005. A total
      of 757 symptomatic cucurbit and 31 weed species were collected and assayed for
      infection with WMV. Of 788 leaf samples from cucurbit and weed plants, 190
      samples were positive by double antibody sandwich ELISA (DAS-ELISA) using
      specific polyclonal antibody. Among the weed species tested only colocynth
      (Citrullus colocynthis) was found to be infected with WMV. The coat protein (CP)
      gene from 18 representative isolates was PCR amplified, cloned, sequenced, and
      compared with the sequences available in GeneBank. Phylogenetic analysis using
      778 nucleotide long sequences of the coat protein gene showed that these isolates
      fell into two; groups I and II. Only one isolates (KER.JI.1) was classified in
      the group II. This isolate had a wider host range and infected Nicotiana debneyii
      and Datura metel. None of the other 17 isolates could infect these two species.
      Members of group I were divided into three subgroups; A, B, and C. The subgroup
      I(B) appears to be a new subgroup comprising only of the Iranian isolates.
      Phylogenetic analysis based on 200 nucleotides coding for the N-terminal segment
      of the CP showed that all Iranian isolates except KER.JI.1 clustered with the
      previously reported WMV strains. All Iranian isolates had a DAG amino acid
      triplet which is involved in aphid transmissibility. This is the first report on
      sequence analysis of the nearly full-length CP cDNA clones of WMV isolates from
      Iran.

PMID- 18712589
TI  - Genetic characterization of avian influenza viruses isolated in Israel during
      2000-2006.
AB  - Our aim was to establish the phylogenetic and genetic relationships among avian
      influenza viruses (AIV) recently isolated from poultry in Israel. During this
      study we analyzed complete nucleotide sequences of two envelope (hemagglutinin
      and neuraminidase) and six internal genes (polymerase B1, polymerase B2,
      polymerase A, nucleoprotein, nonstructural, and matrix) of 29 selected H9N2 and
      six internal genes of five H5N1 viruses isolated in Israel during 2000-2006.
      Comparative genetic and phylogenetic analyses of these sequences revealed that
      the local H5N1 viruses are closely related to H5N1 viruses isolated in European,
      Asian, and Middle Eastern countries in 2005-2006. The H9N2 Israeli isolates,
      together with viruses isolated in Jordan and Saudi Arabia formed a single group.
      Our data support the claim that during recent years a new endemic focus of H9N2
      has been formed in the Middle East. The introduction of H5N1 and co-circulation
      of these two subtypes of AIV in this region may augment the risk of potentially
      pandemic strains emergence.

PMID- 18712591
TI  - Optimism, social support, and adjustment in African American women with breast
      cancer.
AB  - Past studies show that optimism and social support are associated with better
      adjustment following breast cancer treatment. Most studies have examined these
      relationships in predominantly non-Hispanic White samples. The present study
      included 77 African American women treated for nonmetastatic breast cancer. Women
      completed measures of optimism, social support, and adjustment within 10-months
      of surgical treatment. In contrast to past studies, social support did not
      mediate the relationship between optimism and adjustment in this sample. Instead,
      social support was a moderator of the optimism-adjustment relationship, as it
      buffered the negative impact of low optimism on psychological distress, well
      being, and psychosocial functioning. Women with high levels of social support
      experienced better adjustment even when optimism was low. In contrast, among
      women with high levels of optimism, increasing social support did not provide an
      added benefit. These data suggest that perceived social support is an important
      resource for women with low optimism.

PMID- 18712592
TI  - Effects of genetic background, gender, and early environmental factors on
      isolation-induced ultrasonic calling in mouse pups: an embryo-transfer study.
AB  - Infant rodents emit ultrasonic vocalizations when isolated from dam and
      littermates. Due to the context of their occurrence and the well described
      bidirectional modulation by substances known for their capability to influence
      emotionality, it was postulated that such calls reflect a negative affective
      state akin anxiety. Comparative studies observed pronounced differences in
      calling behavior between strains, which were paralleled by differences in
      maternal care. Therefore, it was recently hypothesized that early environmental
      factors may have strong impact on call production. Here, the relative
      contributions of genetic background, gender, and early environmental factors on
      calling behavior in C57BL/6JOlaHsd and C57BL/6NCrl were studied by using an
      embryo-transfer procedure. The results show that these sub-strains differ in the
      amount of calling and specific call features, like call frequency and amplitude.
      The embryo-transfer procedure indicated that the observed differences in the
      amount of ultrasonic calling are dependent on the dyadic interaction between
      mother and pup. Conversely, call features were primarily dependent on the
      genotype of the pup. Thus, call frequency and frequency modulation were solely
      dependent on the pup, i.e. its genotype and gender. However, there was one
      exception, namely call amplitude, which was solely dependent on the genotype of
      the mother, i.e. on early environmental factors. Furthermore, it was shown that
      particularly changes in call amplitude might be of high functional relevance,
      since a sub-strain dependent preference towards pups emitting calls with high
      amplitudes was observed. In total, it can be concluded that both genomic and
      nongenomic factors can tune calling behavior in mouse pups.

PMID- 18712593
TI  - Neighborhood-level correlates of consistent condom use among men who have sex
      with men: a multi-level analysis.
AB  - There is growing evidence that the neighborhood environment influences sexual
      behavior and related outcomes, but little work has focused specifically on men
      who have sex with men (MSM). Using interview data from a probability sample of
      385 young MSM living in New York City, recruited at public venues in 1999 and
      2000 as part of the Young Men's Survey-New York City, and data on neighborhood
      characteristics obtained from the U.S. Census 2000, we conducted multi-level
      analyses of the associations between neighborhood-level characteristics and
      consistent condom use during anal intercourse, while controlling for individual
      level sociodemographic and other factors. After adjusting for individual-level
      factors, neighborhood-level gay presence remained significantly and positively
      associated with consistent condom use during anal intercourse. This finding
      suggests that neighborhoods with a significant gay presence may have norms that
      act to discourage high risk sexual activity.

PMID- 18712594
TI  - Parent and adolescent depressive symptoms: the role of parental attributions.
AB  - This study examined whether negative parental attributions for adolescent
      behaviour mediate the association between parental and adolescent depressive
      symptoms, and whether this relationship is moderated by adolescent gender.
      Mothers and fathers and 124 adolescents (76 girls and 48 boys; ages 14 to 18)
      participated. Adolescents were primarily Caucasian, and varied in the level of
      depressive symptoms (with 27% of the sample meeting diagnostic criteria for a
      current unipolar depressive disorder). Parents and adolescents completed measures
      of depressive symptoms, and participated in a videotaped problem-solving
      discussion. After the discussion, each parent watched the videotape and, at 20 s
      intervals, offered attributions for their adolescent's behaviour. Adolescent
      gender moderated the relation between parental attributions and adolescent
      depressive symptoms, with stronger associations for female adolescents. For both
      mothers and fathers, both parental depressive symptoms and negative attributions
      about the adolescent's behaviour made unique contributions to the prediction of
      depressive symptoms in adolescent females. There also was evidence that negative
      attributions partially mediated the link between depressive symptoms in mothers
      and adolescent daughters. The results are interpreted as consistent with
      parenting as a partial mediator between parental and adolescent depressive
      symptoms, and suggest that adolescent girls may be particularly sensitive to
      parents' negative interpretations of their behaviour.

PMID- 18712595
TI  - Weekly epirubicin in the treatment of gestational breast cancer (GBC).
AB  - BACKGROUND: GBC is a rare disease and chemotherapy in this setting lacks a
      standardized approach. PATIENTS AND METHODS: Patients 16-30 weeks pregnant with
      locally advanced/metastatic disease or with high risk of recurrence after surgery
      were evaluated. RESULTS: Twenty patients received weekly epirubicin 35 mg/m(2).
      Median maternal age was 37 years (23-42). Median gestational age at chemotherapy
      was 19 weeks. Thirteen patients were treated after surgery while 7 had locally
      advanced tumours of which one had liver metastases. Mean total epirubicin dose
      was 420 mg/m(2) with a median number of 12 administrations (4-16). No grade 3-4
      toxicities were observed. No foetal adverse events were observed except 1
      premature delivery at 28 weeks. Births were induced by caesarean section in 12
      patients at a median gestational age of 35 weeks. No malformations were reported
      except 1 newborn with polycystic kidney. At a median age of 2 years,
      neurological, cardiological and immunological development was normal in all
      children as reported by their parents. In 7/20 patients with evaluable disease,
      five had an objective response. At a median follow-up of 38 months, 17 patients
      are alive; 14 are disease free. CONCLUSIONS: Weekly epirubicin appears safe and
      effective with low foetal toxicity and could be considered in GBC.

PMID- 18712596
TI  - Vitreo-retinal traction and anastrozole use.
AB  - PURPOSE: This study tested a prediction stemming from the hypothesis that
      anastrozole users experience heightened vitreo-retinal traction. This hypothesis
      was based on the knowledge that menopause increases the risk of intraocular
      tractional events such as posterior vitreous detachments (PVDs). METHODS: Retinal
      thickness was measured for 3 groups of amenorrheic women: (1) anastrozole users
      and (2) tamoxifen users undergoing adjuvant therapy for early-stage breast
      cancer, and (3) control subjects not using hormonal medication. Foveal shape
      indices were derived for subjects without PVDs. RESULTS: For anastrozole users,
      the distance to the temporal side of the fovea became less than the distance to
      the nasal side at a sufficient height above the foveal base. This effect did not
      exist for control subjects; the between-group difference was appreciable. Results
      concerning tamoxifen users were inconclusive. CONCLUSIONS: The foveas of women
      using anastrozole appear to be subjected to more tractional force than are the
      foveas of women not using any hormonal medication.

PMID- 18712598
TI  - Adenine nucleotide hydrolysis in patients with aseptic and bacterial meningitis.
AB  - The meningitis is a disease with high mortality rates capable to cause neurologic
      sequelae. The adenosine (the final product of ATP hydrolysis by
      ectonucleotidases), have a recognized neuroprotective actions in the central
      nervous system (CNS) in pathological conditions. The aim of the present study was
      evaluate the adenine nucleotides hydrolysis for to verify one possible role of
      ATP, ADP and AMP hydrolysis in inflammatory process such as meningitis. The
      hydrolysis was verified in cerebrospinal fluid (CSF) from human patients with
      aseptic and bacterial meningitis. Our results showed that the ATP hydrolysis was
      reduced 12.28% (P < 0.05) in bacterial meningitis and 22% (P < 0.05) in aseptic
      meningitis. ADP and AMP hydrolysis increased 79.13% (P < 0.05) and 26.37% (P <
      0.05) in bacterial meningitis, respectively, and 57.39% (P < 0.05) and 42.64% (P
      < 0.05) in aseptic meningitis, respectively. This may be an important protective
      mechanism in order to increase adenosine production.

PMID- 18712597
TI  - Effects of chronic restraint stress and estradiol replacement on glutamate
      release and uptake in the spinal cord from ovariectomized female rats.
AB  - Glutamate is an excitatory neurotransmitter involved in neuronal plasticity and
      neurotoxicity. Chronic stress produces several physiological changes on the
      spinal cord, many of them presenting sex-specific differences, which probably
      involve glutamatergic system alterations. The aim of the present study was to
      verify possible effects of exposure to chronic restraint stress and 17beta
      estradiol replacement on [3H]-glutamate release and uptake in spinal cord
      synaptosomes of ovariectomized (OVX) rats. Female rats were subjected to OVX, and
      half of the animals received estradiol replacement. Animals were subdivided in
      controls and chronically stressed. Restraint stress or estradiol had no effect on
      [3H]-glutamate release. The chronic restraint stress promoted a decrease and
      17beta-estradiol induced an increase on [3H]-glutamate uptake, but the uptake
      observed in the restraint stress +17beta-estradiol group was similar to control.
      Furthermore, 17beta-estradiol treatment caused a significant increase in the
      immunocontent of the three glutamate transporters present in spinal cord.
      Restraint stress had no effect on the expression of these transporters, but
      prevented the 17beta-estradiol effect. We suggest that changes in the
      glutamatergic system are likely to take part in the mechanisms involved in spinal
      cord plasticity following repeated stress exposure, and that 17beta-estradiol
      levels may affect chronic stress effects in this structure.

PMID- 18712599
TI  - Axonal transport of zinc transporter 3 and zinc containing organelles in the
      rodent adrenergic system.
AB  - Zinc is the second most abundant trace metal (after iron) in mammalian tissues,
      and it is an essential element for growth, development, DNA synthesis, immunity,
      and other important cellular processes. A considerable amount of zinc in the
      brain exists as a pool of free or loosely bound zinc ions in synaptic vesicles
      with zinc transporter 3 (ZnT3) in their membranes. Here we demonstrate that also
      in the peripheral sympathetic nervous system zinc handling neurons exist. In
      autonomic ganglia of rats and mice a subset of neuronal cell bodies contain zinc,
      visualized by the autometallographic (AMG) and TSQ histochemical methods. The Zn
      transporter 3 is, as shown by immunofluorescence, also present in tyrosine
      hydroxylase (TH)-positive neurons, but rarely in cell bodies with neuropeptide Y
      (NPY)-immunoreactivity (IR). In axons of crush-operated sciatic nerves a rapid
      bidirectional accumulation of AMG granules occurred. Also ZnT3-IR was found to
      accumulate rapidly in anterograde as well as retrograde direction, colocalized
      with TH-IR. So far nerve terminals with ZnT3-IR have not been observed. The
      functional significance of zinc ions in the sympathetic system is not known.

PMID- 18712602
TI  - The effects of combined treatment of antioxidants on the liver injury in STZ
      diabetic rats.
AB  - The aim of this study was to examine whether an antioxidant combination of
      vitamin C, vitamin E, and sodium selenate (Se) has an effect on the liver of
      diabetic rats. Vitamin C, vitamin E, and Se were administered for 30 days to
      streptozotocin (STZ)-induced diabetic and control groups. In the STZ diabetic
      group, blood glucose levels, liver lipid peroxidation (LPO), and nonenzymatic
      glycosylation (NEG) levels increased, but blood and liver glutathione levels
      decreased. On the other hand, combined antioxidant treatment reversed these
      effects. In the diabetic group, some degenerative changes were observed by light
      and electron microscopic examinations, but the degenerative changes decreased in
      the diabetic group given antioxidant combination. Proliferating cell nuclear
      antigen (PCNA) immunohistochemistry showed that the number of proliferative
      hepatocytes increased significantly with antioxidant treatment. It was concluded
      that combined treatment with vitamin C, vitamin E, and Se has a curative effect
      against the hepatotoxicity produced by STZ-induced diabetes.

PMID- 18712601
TI  - Midkine mRNA is overexpressed in pancreatic cancer.
AB  - PURPOSE: Midkine (MK) has been reported to be a possible molecular marker for the
      diagnosis of pancreatic cancer. We investigated the feasibility of quantitative
      analysis of MK mRNA by quantitative real-time RT-PCR (qRT-PCR) as a promising
      tool for the diagnosis of pancreatic cancer. RESULTS: We found that pancreatic
      cancer tissues expressed significantly higher levels of MK mRNA than intraductal
      pancreatic mucinous neoplasm (IPMN) and non-neoplastic pancreatic tissues (P <
      0.05); in contrast, we did not find any differences in MK mRNA expression between
      IPMN and non-neoplastic pancreatic tissues. Additionally, we observed that poorly
      differentiated carcinoma samples expressed higher levels of MK mRNA than well
      differentiated carcinoma samples, although a significant difference was not
      observed. CONCLUSIONS: The present data suggests that quantitative analysis of MK
      mRNA provides an objective and sensitive evaluation and may be a promising
      modality for the diagnosis of pancreatic cancer and the prediction of its
      prognosis.

PMID- 18712603
TI  - Understanding the barriers that reduce the effectiveness of HIV/AIDS prevention
      strategies for Puerto Rican women living in low-income households in Ponce, PR: a
      qualitative study.
AB  - BACKGROUND: The HIV/AIDS epidemic has been strongly felt in Hispanic/Latino
      communities. Estimates of AIDS prevalence among Latinos in the US reveal that
      just nine States and the Commonwealth of Puerto Rico account for 89% of the
      Latinos living with AIDS in 2004. Previous research reveals social and cultural
      factors play an important role in HIV prevention. METHODS: Four focus groups were
      conducted, with 39 women, ages 21-67, participating in the discussions. The
      objectives of this research were to assess knowledge regarding HIV transmission
      among women living in low-income households, to ascertain barriers to safe sex in
      this population, and to elicit opinions about effective prevention strategies.
      RESULTS: Our results suggest that participants recognized HIV/AIDS modes of
      transmission and risk behaviors, as well as their barriers to practicing safe
      sex. They identified promiscuity, unprotected sex, infidelity, drug and alcohol
      use, and sharing syringes as behaviors which would place them at risk of HIV/AIDS
      transmission. They specifically identified lack of negotiating skills, fear of
      sexual violence, partner refusal to use condoms, and lack of control over their
      partner's sexual behavior as barriers to practicing safe sex. Finally results
      also indicate that current HIV/AIDS prevention strategies in Puerto Rico are
      inadequate for these women. DISCUSSION: To address these issues the authors
      suggest cultural and social factors to be considered for the development of more
      effective HIV/AIDS prevention programs.

PMID- 18712604
TI  - Slavic women's understanding of diabetes dietary self-management and reported
      dietary behaviors.
AB  - BACKGROUND: Slavic women with type 2 diabetes are an understudied group for
      issues related to dietary self-management for diabetes and heart health. METHODS:
      A single home or extension office visit was conducted with ten Slavic women for
      an individual in-depth interview, clinical and physical assessment, and a survey
      questionnaire. RESULTS: Participants were in poor diabetes control. They reported
      changes in traditional foods to better support diabetes control and heart health.
      Most appeared responsive to their health care provider's recommendations and
      valued cooking classes from a Russian-speaking educator. Barriers included
      perceived expense of a healthy diet. Cultural bridges between patients and their
      caregivers were critical supports for self-management. DISCUSSION AND
      CONCLUSIONS: Support of Slavic women with diabetes should include health care
      providers knowledgeable about Slavic dietary and health concepts, Russian
      speaking educators who can bridge between traditional foodways and the U.S. food
      system, and appropriate involvement of the patient's social support network.

PMID- 18712600
TI  - Evidence-based kernels: fundamental units of behavioral influence.
AB  - This paper describes evidence-based kernels, fundamental units of behavioral
      influence that appear to underlie effective prevention and treatment for
      children, adults, and families. A kernel is a behavior-influence procedure shown
      through experimental analysis to affect a specific behavior and that is
      indivisible in the sense that removing any of its components would render it
      inert. Existing evidence shows that a variety of kernels can influence behavior
      in context, and some evidence suggests that frequent use or sufficient use of
      some kernels may produce longer lasting behavioral shifts. The analysis of
      kernels could contribute to an empirically based theory of behavioral influence,
      augment existing prevention or treatment efforts, facilitate the dissemination of
      effective prevention and treatment practices, clarify the active ingredients in
      existing interventions, and contribute to efficiently developing interventions
      that are more effective. Kernels involve one or more of the following mechanisms
      of behavior influence: reinforcement, altering antecedents, changing verbal
      relational responding, or changing physiological states directly. The paper
      describes 52 of these kernels, and details practical, theoretical, and research
      implications, including calling for a national database of kernels that influence
      human behavior.

PMID- 18712605
TI  - Evaluation of a drift flux model for simulating submicrometer aerosol dynamics in
      human upper tracheobronchial airways.
AB  - In this study, a hybrid drift flux velocity correction (DF-VC) model that
      accounts for both submicrometer particle diffusion and inertia was extended to
      transient conditions and was tested against existing experimental deposition data
      measured in a replica cast of the human tracheobronchial (TB) region for laminar
      and turbulent flow. To evaluate the effectiveness of the DF-VC model, deposition
      results were compared with a standard chemical species (CS) approach that
      neglects particle inertia. A numerical model of the TB cast was constructed from
      CT images and extended from the larynx to approximately the sixth respiratory
      generation. Experimentally determined inlet and outlet flow conditions were
      implemented in the computational model to ensure direct comparisons between
      simulations and measurements for the deposition of 40 and 200 nm particles. A low
      Reynolds number k-omega turbulence model was employed to resolve the laminar and
      turbulent flow regimes that coexist in the TB geometry. Interesting flow
      characteristics were observed due to the presence of the larynx, asymmetrical
      ventilation, and left-right asymmetry, which created a right-skewed laryngeal jet
      and flow reversal in the trachea that persist over a majority of the transient
      flow cycle. In comparison with the CS model, deposition results of the DF-VC
      approach persistently agreed better with experimental findings on a total and sub
      branch basis, which indicated that the DF-VC model effectively captured the
      influence of finite particle inertia. For the submicrometer aerosols considered,
      transient flows were observed to increase deposition arising from impaction and
      decrease deposition arising from diffusion on a total and segmental basis
      compared with steady state conditions. However, the maximum deposition
      enhancement factor was significantly increased under transient conditions for
      both 40 nm (factor of 2) and 200 nm (factor of 7) aerosols. Results of this study
      indicate that a drift flux particle transport model with near-wall velocity
      corrections can provide an effective continuous-field approach for simulating the
      transport and deposition of submicrometer respiratory aerosols in human upper TB
      airways.

PMID- 18712606
TI  - Exothermic reaction in zeolite hemostatic dressings: QuikClot ACS and ACS+.
AB  - BACKGROUND: Zeolites have hemostatic properties used to stop bleeding in severe
      hemorrhage. Manufactured QuikClot is an approved zeolite-based hemostatic agent
      for battlefield use. The exothermic reaction associated with QuikClot as loose
      granules or as granules packaged in a mesh bag has potential burn effects; this
      led to the development of a formulation of "cooler" non-exothermic QuikClot. The
      goal of this study was to compare the elevation of temperature of these
      formulations upon contact with blood. METHODS: Following full transection of the
      femoral vasculature, anesthetized Yorkshire pigs (n = 15) (28.8 +/- 1.5 kg) were
      hemorrhaged for 2 min and treated with 100 g of bagged QuikClot (Advanced
      Clotting Sponge (ACS) (n = 4)) or a modified non-exothermic formulation (ACS+ (n
      = 11)). Vital signs and temperature at the dressing/tissue interface were
      continuously recorded for 3 h. Additional procedures were used to examine effects
      of different ratios of blood to zeolite on temperature elevation. RESULTS: Total
      post-treatment blood loss was comparable for ACS+_E and ACS_E groups (overall
      average: 18.6 +/- 10.5% EBV). Temperature recorded at the dressing/tissue
      interface was significantly lower with ACS+ vs. ACS (40.3 +/- 1.8 vs. 61.4 +/-
      10.7 degrees C, respectively, p < 0.01) and was 3.2 +/- 2.6 degrees C higher than
      rectal temperature (38.0 +/- 0.7 degrees C, p < 0.01). Survival at endpoint (7/11
      vs. 4/4) and average survival time (134 +/- 64 vs. 180 min) were greater for both
      ACS+ and ACS in comparison to Standard Dressing. The wound temperature with ACS
      was reduced with greater blood to product ratios and this pattern was paralleled
      with in vitro measurements. CONCLUSIONS: The lower heat release with ACS+
      compared to ACS was confirmed in an animal model and ACS+ had similar efficacy in
      arresting bleeding when compared to Standard Dressing.

PMID- 18712607
TI  - Enhancing physical well-being and overall quality of life among underserved
      Latina-American cervical cancer survivors: feasibility study.
AB  - INTRODUCTION: Evidence for the effectiveness of behavioral interventions are
      lacking for cervical cancer survivors (CCS). Disparities in survivorship outcomes
      exist for CCS, especially Latina-Americans. This study assessed the feasibility
      of implementing a culturally sensitive intervention delivered in a telephonic
      format. METHODS: A convenience sample of 23 Latina-Americans diagnosed with
      stages 1-3 invasive cervical cancer who were 1-3 years post diagnosis and disease
      free participated. A random assignment, pre- and post-test design was used with
      15 intervention and 8 control participants. Intervention group participants
      completed 6 sessions that included problem-focused, telephone counseling. The
      areas covered included family and partner concerns and communication; relaxation
      and stress management; psychological, medical and treatment concerns; and self
      nurturing activities. Outcomes were measured by the FACT-G QOL scale. RESULTS:
      Increases in physical well-being and overall QOL were observed for the
      intervention group only (p < 0.05). The intervention group showed a non
      significant trend towards improvements in family/social, emotional and functional
      well-being from pre- to post-test. DISCUSSION: Results demonstrate the
      feasibility of implementing a culturally responsive, telephonic behavioral
      intervention. The intervention was associated with an improvement in physical and
      overall quality of life. A randomized controlled trial with a long term follow-up
      is warranted. IMPLICATIONS FOR CANCER SURVIVORS: An ethnically sensitive,
      behaviorally based telephone counseling approach with Latina Americans cervical
      cancer survivors can achieve short term improvements in physical well-being and
      overall QOL.

PMID- 18712608
TI  - Protection of Metarhizium anisopliae conidia from ultra-violet radiation and
      their pathogenicity to Rhipicephalus evertsi evertsi ticks.
AB  - Metarhizium anisopliae conidia were formulated in water or in olive oil
      containing 3% commercial sunscreens (Everysun or E45 Sun Block 50) and exposed to
      an artificial UV source for up to 5 hours. Survival of conidia after 5 h of
      exposure to UV in oil formulation was 29% when protected with Everysun, 40% when
      protected with E45, and 4% in control. In comparison, survival of conidia
      formulated in water was 13% when protected with Everysun, 24% when protected with
      E45, and 0% in control. Furthermore, the influence of sunscreens on conidia
      viability and virulence to Rhipicephalus evertsi evertsi larvae and unfed adult
      ticks was evaluated. Adding these compounds to the conidial formulations did not
      reduce the viability of the conidia. Larval mortality was 95 and 100%, while
      unfed adult mortality was 90 and 97% after being exposed to unprotected conidia
      formulated in water or in oil, respectively. Conidia protected by Everysun or E45
      formulated in water, induced 88 and 83% mortality in larvae, and 92 and 90%
      mortality in unfed adults, respectively. Conidia suspended in oil and protected
      by Everysun or E45 induced 94 and 91% mortality in larvae, and 83 and 81% in
      unfed adults, respectively. These observations indicate that olive oil and the
      two sunscreens confer protection to conidia against damages by UV radiation
      without interfering with their pathogenicity to ticks.

PMID- 18712609
TI  - Sinusoidal tumor angiogenesis is a key component in hepatocellular carcinoma
      metastasis.
AB  - Hepatocellular carcinoma (HCC) has a tendency for intravascular dissemination
      leading to a poor prognosis. The importance of the sinusoidal structure of the
      tumor vasculature in HCC has been implicated in the metastasis formation. To
      clarify the role of tumor angiogenesis in HCC metastasis, we morphologically
      investigated the interaction of HCC cells with blood vessels during the
      sequential process of metastasis. Autopsy specimens of 80 patients with HCC were
      examined with immunohistochemistry using a specific antibody against CD31, a
      marker for endothelial cells. The most frequent sites of metastasis were the
      liver (82.5%) and lung (43.8%). In most cases, the metastatic process was
      initiated by vascular involvement where tumor nests surrounded by sinusoidal
      vessels extend into the portal and hepatic veins. Subsequently, these endothelial
      coated tumor emboli enter the circulation, embolize at distant organs,
      proliferate within the blood vessel and ultimately form metastatic foci. These
      steps are indicative of an invasion-independent pathway. Our findings in animal
      models and now in human cases suggest that sinusoidal angiogenesis may represent
      a novel target for therapeutic strategies to limit HCC metastasis. In combination
      with primary tumor treatment, perturbation of tumor emboli may reduce
      dissemination of disease.

PMID- 18712610
TI  - Landscape scale ecological monitoring as part of an EIA of major construction
      activities: experience at the Turkish section of the BTC crude oil pipeline
      project.
AB  - Ecological monitoring is a complementary component of the overall environmental
      management and monitoring program of any Environmental Impact Assessment (EIA)
      report. The monitoring method should be developed for each project phase and
      allow for periodic reporting and assessment of compliance with the environmental
      conditions and requirements of the EIA. Also, this method should incorporate a
      variance request program since site-specific conditions can affect construction
      on a daily basis and require time-critical application of alternative
      construction scenarios or environmental management methods integrated with
      alternative mitigation measures. Finally, taking full advantage of the latest
      information and communication technologies can enhance the quality of, and public
      involvement in, the environmental management program. In this paper, a landscape
      scale ecological monitoring method for major construction projects is described
      using, as a basis, 20 months of experience on the Baku-Tbilisi-Ceyhan (BTC) Crude
      Oil Pipeline Project, covering Turkish Sections Lot B and Lot C. This analysis
      presents suggestions for improving ecological monitoring for major construction
      activities.

PMID- 18712611
TI  - Hurricane Katrina-induced forest damage in relation to ecological factors at
      landscape scale.
AB  - Forest stand stability to strong winds such as hurricanes has been found to be
      associated with a number of forest, soil and topography factors. In this study,
      through applying geographic information system (GIS) and logit regression, we
      assessed effects of forest characteristics and site conditions on pattern,
      severity and probability of Hurricane Katrina disturbance to forests in the Lower
      Pearl River Valley, USA. The factors included forest type, forest coverage, stand
      density, soil great group, elevation, slope, aspect, and stream buffer zone.
      Results showed that Hurricane Katrina damaged 60% of the total forested land in
      the region. The distribution and intensity of the hurricane disturbance varied
      across the landscape, with the bottomland hardwood forests on river floodplains
      most severely affected. All these factors had a variety of effects on
      vulnerability of the forests to the hurricane disturbance and thereby spatial
      patterns of the disturbance. Soil groups and stand factors including forest
      types, forest coverage and stand density contributed to 85% of accuracy in
      modeling the probability of the hurricane disturbance to forests in this region.
      Besides assessment of Katrina's damage, this study elucidates the great
      usefulness of remote sensing and GIS techniques combined with statistics modeling
      in assessment of large-scale risks of hurricane damage to coastal forests.

PMID- 18712612
TI  - Monitoring genotoxicity among gasoline station attendants and traffic enforcers
      in the City of Manila using the micronucleus assay with exfoliated epithelial
      cells.
AB  - Some types of occupations involve high levels of exposure to potentially
      genotoxic gaseous and particulate substances from internal combustion engines
      used in motor vehicles. These occupational exposures may contribute to the
      development of many illnesses, usually through chromosomal change mechanisms that
      include strand breakage, deletions, sister chromatid exchange and non
      disjunction. To determine the effect of occupational exposure in gasoline station
      attendants and traffic enforcers, the micronucleus test was used. Exfoliated oral
      mucosa cells from 18 gasoline station attendants, 18 traffic enforcers and 18
      control subjects in the City of Manila were examined for micronucleated cell
      (MNC) frequency. Analysis of buccal cells showed that MNC frequencies in exposed
      individuals were significantly greater than in control subjects (p < or = 0.05).
      However, between gasoline station attendants and traffic enforcers, MNC
      frequencies of the two exposed groups exhibited no significant difference. No
      relation was also found between MNC frequency and any of the factors such as age,
      smoking habits, alcohol habits and working period. This was further confirmed in
      the multiple regression analysis which showed that only occupational exposure was
      a good predictor of MNC frequency. The results of this study suggest that
      gasoline station attendants and traffic enforcers, compared to the control
      individuals, are at a greater risk of chromosomal damage. For the assessment of
      chromosomal damage, the study, development, and standardization of tests are
      recommended for public institutions concerned with matters regarding
      environmental quality and community health.

PMID- 18712613
TI  - Effect of water quality parameters on the distribution of Pleuromamma (Copepoda
      Calanoida) species in the Indian Ocean: a statistical approach.
AB  - The region between 10 degrees N and 10 degrees S latitude was known to be
      congenial for distribution of Pleuromamma species. Diel and ontogenetic
      migrations were observed for Pleuromamma xiphias. Multivariate analyses such as
      factor analysis on species' abundance and predictive step-up multiple regression
      models of water quality parameters: temperature, salinity, dissolved oxygen and
      their first order interaction effects on Pleuromamma species' abundance, were
      carried out in the regions, off 10 degrees N, 10 degrees N to 10 degrees S, 10
      degrees S to 30 degrees S, along the Somali Coast (38 degrees S-40 degrees S) and
      a fifth region along the western boundary of the above four regions. Relation
      between Pleuromamma species' abundance and the water quality parameters showed a
      decreasing trend in the variability explained (VE) from region 1 (VE = 55.19%) to
      region 4 (VE = 31.15%) in the models, indicating that the influence of other
      ecological factors was of higher significance in the south than in the north,
      with a north south gradient. Indices of diversity (Shannon-Weaver) and evenness
      (Heips) were calculated and lognormal distributions fitted for these indices were
      found to be a good fit (p < 0.05). The five regions were compared, based on
      critical ratio of the diversity index. Shannon-Weaver diversity showed higher
      values during night collections than day collections, justifying the tendency for
      diurnal variations. Diversity and dominance were highly (r = 0.95) correlated. A
      multilinkage cluster analysis by group averaging method for the species, based on
      the standardised values of log(10) (X + 1) transformed species' abundance, showed
      that Pleuromamma indica, Pleuromamma gracilis and Pleuromamma abdominalis were
      not segregated in any of the five regions. Bray and Curtis (1957) coefficient of
      similarity for the species in the five regions combined together, showed 50%
      similarity for the cluster containing circum-global species, Pleuromamma piseki,
      P. gracilis, P. abdominalis and P. borealis. The species, P. indica and P.
      xiphias entered this cluster at 22% similarity level. Multivariate factor
      analysis by row normalisation (for species) and column normalisation (for
      stations), using varimax rotation to simple structure for unique grouping of
      species as well as stations, carried out in the five regions, showed that the
      maximum number of species' clusters were obtained in region 2, indicating a
      higher variability in the ecological conditions in this region than in the other
      four regions. The significance of the factor model and the differential factor
      groups of species were also determined in the studied regions. On a broader
      scale, based on the ecological aspect, the first four regions could be reduced to
      two regions, viz, region 1 including the north off 10 degrees N, Central Indian
      Ocean and the area of subtropical convergence, and region 2 consisting
      exclusively of the equatorial region between 10 degrees N and 10 degrees S based
      on distribution of Pleuromamma species. The plot of the species abundance with
      respect to latitude also showed such a demarcation.

PMID- 18712614
TI  - Contemporary estimates of atmospheric nitrogen deposition to the watersheds of
      New York State, USA.
AB  - Atmospheric inputs of reactive nitrogen (N) to ecosystems are a particular
      concern in the northeastern USA, including New York State, where rates of
      atmospheric N deposition are among the highest in the nation. We calculate the
      seasonal and annual spatial variations of contemporary inorganic atmospheric N
      deposition loading to multi-scale watersheds across New York State using numerous
      monitoring datasets of precipitation and ambient atmospheric N concentrations.
      Our models build upon and refine previous efforts estimating the spatial
      distribution of N deposition. Estimates of total inorganic wet deposition (NH4-N
      + NO3-N) across New York ranged from 4.7 to 10.5 kg ha(-1) yr(-1) under
      contemporary conditions (averaged 2002-2004), and both seasonal and annual
      predicted rates of inorganic N deposition (NH4-N, NO3-N, and total) fit
      relatively well with that of observed measurements. Our results suggest that "hot
      spots" of N deposition are, for the most part, spatially distributed according to
      geographic positions (i.e., relative location from sources and the Great Lakes
      system) and elevation. We also detect seasonal variations in deposition, showing
      that total wet atmospheric inorganic N deposition inputs to watersheds (extracted
      from the four-digit HUC calculations) are highest during the spring (mean = 2.4
      kg ha(-1), stddev = 0.29) and lowest during the winter months (mean = 1.4 kg ha(
      1), stddev = 0.23). Results also suggest that wet NO3(-) consistently comprises a
      slightly higher proportion of wet N deposition than wet NH4+ throughout
      watersheds of New York, ranging from 2.5 to 6.1 kg NO3-N ha(-1) yr(-1) compared
      to NH4+, which ranges from 2.2 to 4.4 kg NH4-N ha(-1) yr(-1).

PMID- 18712615
TI  - Productive and metabolic consequences induced by the retained placenta in dairy
      cows.

PMID- 18712616
TI  - Investigation of the metabolic activity of a bovine mammary epithelial cell line
      (BME-UV1).
AB  - The metabolic activity of a mammary epithelial cell line (BME-UV1) was evaluated
      on monolayers exposed, in serum free medium, to different concentrations (2-4-8
      muM) of aflatoxin B1 (AFB1), a mycotoxin eliminated into milk especially as
      hydroxylated metabolite aflatoxin M1 (AFM1). After 4, 8, 12, 24 h of treatment, a
      dose and time dependent production of AFM1 has been detected. As the enzymes
      involved in the hydroxylation of AFB1 in bovine hepatocytes are mainly CYP1A and
      CYP3A, the results suggest that BME-UV1 express CYP450 isoenzymes which
      metabolize AFB1 thus representing a potential model for the investigation of the
      metabolic activity of bovine mammary epithelial tissue.

PMID- 18712617
TI  - Preparation of biodegradable polycaprolactone/poly (ethylene
      glycol)/polycaprolactone (PCEC) nanoparticles.
AB  - Biodegradable polyetherester copolymer (PCL/PEG/PCL, PCEC) was synthesized by
      ring-opening polymerization of epsilon-caprolactone initiated by poly(ethylene
      glycol) (PEG). The PCEC nanoparticles were prepared by solvent diffusion method
      or w/o/w double emulsion method. The obtained particles' morphology was observed
      on scanning electron microscopy, and the particle size distribution was
      determined using Malvern laser particle sizer. Bovine serum albumin was used as
      the model water-soluble protein drug, which was successfully encapsulated in PCEC
      nanoparticles, the drug release behavior was studied in detail. The hydrolytic
      degradation behavior of the PCEC nanoparticles was also studied.

PMID- 18712618
TI  - Evaluation of chitosan gel as antibiotic and photosensitizer delivery.
AB  - This work suggests the use of chitosan gel imbued with the photosensitizer
      Photogem and with the antibiotic Tetraclin as a possible drug delivery system.
      The results reveal a decrease in the photosensitizer level of toxicity. Besides,
      the interaction between Photogem and chitosan gel causes a red shift in the
      photosensitizer spectrum, increasing its absorption in the therapeutic window
      (600-700 nm). These characteristics indicate this compound as a promising natural
      polymer-based photosensitizer carrier for photodynamic therapy. In summary, our
      results show that pure and doped chitosan gel may have potential application for
      antimicrobial action, being an excellent alternative when local control of the
      drug administration, provided by the gel, is required.

PMID- 18712619
TI  - Enhanced controlled release of loratadine from the ethylene-vinyl acetate matrix
      containing plasticizer.
AB  - An ethylene-vinyl acetate (EVA) matrix containing plasticizer was prepared as a
      potential controlled release system for loratadine. The EVA matrix containing
      loratadine was prepared as the transdermal device using casting methods. The
      solubility of loratadine according to the volume fraction of PEG 400 was
      determined. The effects of the drug concentration, temperature, and plasticizers
      on the release of the drug were determined at 37 degrees C using 40% PEG 400
      solution as the receptor medium using the modified Keshary-Chien cell. Some types
      of plasticizers. such as citrates and phthalates, were used to prepare the pores
      and increase the flexibility of the EVA matrix. The solubility test according to
      the PEG 400 volume fraction revealed the highest solubility in the 40% PEG 400
      solution. The rate of drug released from the EVA matrix increased with increasing
      temperature and drug loading. There was a linear relationship between the release
      rate and the square root of the loading dose. The activation energy for drug
      release from the EVA matrix with a loading dose of 1%, 2%, 3%, 4%, and 5% was
      estimated to be 6.83, 6.80, 6.77, 6.71, and 6.65 kcal/mol, respectively Among the
      plasticizers used, diethyl phthalate showed the highest level of loratadine
      release. In conclusion, an EVA matrix containing plasticizer could be used to
      enhance the controlled release of loratadine.

PMID- 18712620
TI  - Formulation and evaluation of dextromethorphan hydrobromide sustained release
      tablets.
AB  - Sustained release (SR) matrix tablets of dextromethorphan hydrobromide were
      prepared by wet granulation using hydroxypropyl methyl cellulose (HPMC-K-100 CR)
      as the hydrophilic rate controlling polymer. The effect of the concentration of
      the polymer and different fillers on the in vitro drug release rate was studied.
      The studies indicated that the drug release can be modulated by varying the
      concentration of the polymer and the fillers. A complete cross-over
      bioavailability study of the optimized formulation of the developed sustained
      tablets and marketed immediate release tablets was performed on six healthy male
      volunteers. The extent of absorption of drug from the SR tablets was
      significantly higher than that for the marketed dextromethorphan hydrobromide
      tablet because of lower elimination rate and longer half-life.

PMID- 18712621
TI  - Optimization of iontophoretic parameters for the transdermal delivery of
      methotrexate.
AB  - The aim of this work was to study the in vitro factors affecting transdermal
      iontophoretic delivery of methotrexate across hairless rat skin. Initial
      screening studies evaluated the effect of ionic strength and donor concentration.
      A response surface model using factorial design shows an increase in the
      cumulative amount of methotrexate delivered (Y1) with an increase in current
      density (X1) and time of application (X2). However, 10 min iontophoresis and 0.05
      mA/cm2 current density did not show an increase in delivery with an increase in
      current density or time of application, respectively. The factorial design was
      able to identify the optimal parameters that would have been difficult to predict
      with a conventional one at a time-experimental approach.

PMID- 18712622
TI  - Transdermal delivery of carvedilol containing glycyrrhizin and chitosan as
      permeation enhancers: biochemical, biophysical, microscopic and pharmacodynamic
      evaluation.
AB  - The present study was aimed at unveiling the influence of glycyrrhizin and
      chitosan on rat epidermis and to correlate these effects with percutaneous
      permeation characteristics of carvedilol. The permeation of carvedilol across
      excised rat epidermis was significantly higher (p < 0.05) when glycyrrhizin,
      chitosan, or glycyrrhizin-chitosan mixture was used as a donor vehicle as
      compared to propylene glycol:ethanol (7:3) mixture. Epidermis obtained after 12
      hr treatment of viable rat skin with a glycyrrhizin-chitosan mixture showed
      significantly higher (p < 0.05) permeability to carvedilol as compared to that
      after treatment with glycyrrhizin or chitosan alone. Further, the application of
      patches containing glycyrrhizin-chitosan mixture resulted in sustained release of
      carvedilol, which was able to control the hypertension in deoxycorticosterone
      acetate induced hypertensive rats through 28 hr. Estimation of microconstituents
      in rat epidermis revealed maximum extraction of cholesterol, sphingosine, and
      triglycerides after treatment with glycyrrhizin-chitosan mixture. This was
      manifested in altered lipid and protein-specific thermotropic transitions.
      Further, increase in intercellular space, disordered lipid structure and
      corneocyte detachment as observed in SEM and TEM suggests great potential of
      glycyrrhizin for use as a percutaneous permeation enhancer.

PMID- 18712623
TI  - Modeling of caffeine release from crosslinked water-swellable gelatin and gelatin
      maltodextrin hydrogels.
AB  - Research from this group has recently led to the development of a genipin
      crosslinked gelatin gel that may be used as a controlled release matrix for
      bioactive compounds. This study presents a model that simulates the release of
      entrapped caffeine from the hydrogel and the ingress of water into these gels.
      Fick's second law of diffusion is used to describe the water penetration and
      bioactive release in the system. To validate the model, caffeine release
      experiments from the gel were carried out. The predicted bioactive release
      profiles are in very good agreement with experimental data at different gel
      compositions. The model may also be used for a wide range of bioactive molecules
      and hydrogels with different cylindrical dimensions.

PMID- 18712624
TI  - In vitro permeation studies of nanoemulsions containing ketoprofen as a model
      drug.
AB  - We prepared a nanoemulsion system with benzyl alcohol/ ethanol/Solutol/smash(R)
      HS 15 /water. Ketoprofen was used as a model drug in this study. The
      nanoemulsions of this system evidenced a high degree of stability. The droplet
      diameter did not change over a period of at least 3 months. The nanoemulsion
      containing 4% benzyl alcohol evidenced a permeation rate higher than was observed
      with the 1% and 2% nanoemulsions. Also the nanoemulsion containing 1% Solutol(R)
      HS 15 provided a permeation rate higher than was seen with the 2% and 4%
      nanoemulsions. All ketoprofen-loaded nanoemulsions enhanced the in vitro
      permeation rate through mouse skins as compared to the control.

PMID- 18712626
TI  - Abstracts of the American Association of Cancer Education, Cancer Education
      Prevention Network, and European Association of Cancer Education 42nd Annual
      Meeting. October 20-22, 2008. Clearwater, Florida, USA.

PMID- 18712625
TI  - Multi-unit floating alginate system: effect of additives on ciprofloxacin
      release.
AB  - In an attempt to fabricate floating beads of ciprofloxacin, drugloaded alginate
      beads were prepared by simultaneous external and internal gelation. The effect of
      blending of alginate with gellan, hydroxypropyl methylcellulose, starch, and
      chitosan on the bead properties were evaluated. Beads were spherical with
      incorporation efficiency in the range of 52.81 +/- 2.64 to 78.95 +/- 1.92%. Beads
      exhibited buoyancy over a period of 7-24 hr based on the formulation variables.
      In vitro release of ciprofloxacin from the alginate beads in simulated gastric
      fluid (SGF) (0.1 N HCl, pH 1.2), was influenced significantly (p < 0.001) by the
      properties and concentration of additives. Among the polymers incorporated into
      alginate beads. Hydroxy propyl methylcellulose (HPMC) provided an extended
      release over 7 hr. The drug release predominately followed Higuchi's square root
      model.

PMID- 18712627
TI  - Cost-effectiveness analysis of a universal vaccination programme with the 7
      valent pneumococcal conjugate vaccine (PCV-7) in Sweden.
AB  - The 7-valent pneumococcal conjugate vaccine (PCV-7) has proved to be highly
      effective against invasive pneumococcal disease and has also provided some
      protection against all-cause pneumonia and acute otitis media. The objective of
      this study was to evaluate the projected health benefits, costs and cost
      effectiveness of vaccination with the 7-valent conjugated pneumococcal vaccine
      compared with no vaccination, in all infants in Sweden, taking herd immunity into
      account. A Markov model was used and a hypothetical birth cohort was simulated
      for a lifelong perspective. The results show that vaccination of 1 cohort could
      potentially prevent 9 cases of pneumococcal meningitis, 22 cases of pneumococcal
      septicaemia, 509 cases of hospitalized pneumonia, 7812 cases of acute otitis
      media, and 2.7 fatalities, among children 0-4 y of age and 6 episodes of
      pneumococcal meningitis and 167 cases of pneumococcal septicaemia among adults.
      The incremental cost per QALY and LY gained was estimated to Euro 29,200 and Euro
      51,400, respectively. When herd immunity was accounted for, the cost per QALYand
      LY gained was estimated to Euro 5500 and Euro 6600, respectively. Thus, the
      health benefits of a national vaccination programmeme can be achieved within a
      'moderate' or 'low' cost per QALY gained.

PMID- 18712629
TI  - Vitamin E in human health and disease.
AB  - Vitamin E in nature is comprised of a family of tocopherols and tocotrienols. The
      most studied of these is alpha-tocopherol (alpha-TOH), because this form is
      retained within the body, and vitamin E deficiency is corrected with this
      supplement. alpha-TOH is a lipid-soluble antioxidant required for the
      preservation of cell membranes, and it potentially acts as a defense against
      oxidative stress. Many studies have investigated the metabolism, transport, and
      efficacy alpha-TOH in the prevention of sequelae associated with cardiovascular
      disease (CVD). Supplementation with vitamin E is considered to provide health
      benefits against CVD through its antioxidant activity, the prevention of
      lipoprotein oxidation, and the inhibition of platelet aggregation. However, the
      results from large prospective, randomized, placebo-controlled clinical trials
      with alpha-TOH have been largely negative. A recent meta-analysis suggests that
      alpha-TOH supplements may actually increase all-cause mortality; however, the
      mechanism for this increased risk is unknown. In vitro studies performed in human
      cell cultures and animal models suggest that vitamin E might increase the hepatic
      production of cytochrome P450s and MDR1. Induction of CYP3A4 or MDR1 by vitamin E
      could potentially lower the efficacy of any drug metabolized by CYP3A4 or MDR1.
      Other possibilities include an adverse effect of alpha-TOH on blood pressure in
      high-risk populations. Because of the wide popularity and use of vitamin E
      supplements, further research into potential adverse effects is clearly
      warranted.

PMID- 18712630
TI  - Clinical perspectives on hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HH) comprises a group of inherited disorders of iron
      metabolism that can result in progressive iron overload, morbidity, and
      mortality, generally in adulthood. HFE-related HH is the most common type of HH
      and will form the core of this discussion. The discovery of new proteins and gene
      mutations has defined other types of HH, termed non-HFE HH. The regulatory
      protein hepcidin has a central role in iron homeostasis in these disorders. While
      the liver is the predominant organ of iron deposition and iron-overload-related
      disease in HFE-related HH, involvement of extrahepatic tissue can also result in
      morbidity and mortality if the disorder is not diagnosed before organ damage
      develops. This review traverses the road from HFE genotype to phenotype with a
      focus on clinical penetrance, modifier factors for disease expression, and
      current thoughts and controversies on HH diagnosis and screening.

PMID- 18712631
TI  - The oxidation of glutathione by cobalt/tungsten carbide contributes to hard metal
      induced oxidative stress.
AB  - The occupational exposure to cobalt/tungsten carbide (Co/WC) dusts causes asthma
      and interstitial fibrosis. The International Agency for Research on Cancer (IARC)
      recently classified the mixture Co/WC as probably carcinogenic to humans (group
      2A). The mechanism of action of Co/WC involves particle driven generation of
      Reactive Oxygen Species (ROS) with consequent oxidative damage. The present study
      evaluates the reactivity of Co/WC dust toward glutathione (GSH) and cysteine
      (Cys). Co/WC oxidized thiols through a mechanism involving the generation of
      sulphur-centred radicals. The results are consistent with the oxidation taking
      place at surface active sites, a part of which is accessible only to Cys S-H
      groups, but not to GSH ones. Such a reaction, with consequent irreversible
      depletion of antioxidant defenses of cells, will potentiate the oxidative stress
      caused by particle and cell generated ROS.

PMID- 18712632
TI  - The lipocalin alpha1-microglobulin protects erythroid K562 cells against
      oxidative damage induced by heme and reactive oxygen species.
AB  - Alpha(1)-microglobulin is a 26 kDa plasma and tissue glycoprotein that belongs to
      the lipocalin protein superfamily. Recent reports show that it is a reductase and
      radical scavenger and that it binds heme and has heme-degrading properties. This
      study has investigated the protective effects of alpha(1)-microglobulin against
      oxidation by heme and reactive oxygen species in the human erythroid cell line,
      K562. The results show that alpha(1)-microglobulin prevents intracellular
      oxidation and up-regulation of heme oxygenase-1 induced by heme, hydrogen
      peroxide and Fenton reaction-generated hydroxyl radicals in the culture medium.
      It also reduces the cytosol of non-oxidized cells. Endogeneous expression of
      alpha(1)-microglobulin was up-regulated by these oxidants and silencing of the
      alpha(1)-microglobulin expression increased the cytosol oxidation. alpha(1)
      microglobulin also inhibited cell death caused by heme and cleared cells from
      bound heme. Binding of heme to alpha(1)-microglobulin increased the radical
      reductase activity of the protein as compared to the apo-protein. Finally,
      alpha(1)-microglobulin was localized mainly at the cell surface both when
      administered exogeneously and in non-treated cells. The results suggest that
      alpha(1)-microglobulin is involved in the defence against oxidative cellular
      injury caused by haemoglobin and heme and that the protein may employ both heme
      scavenging and one-electron reduction of radicals to achieve this.

PMID- 18712633
TI  - Antioxidants increase number of progenitor endothelial cells through multiple
      gene expression pathways.
AB  - To date, there is no report on the effect of antioxidants on endothelial
      progenitor cells (EPCs). This study shows that in vitro incubation of EPCs with
      vitamin C and E reverted the already well documented lowering effect of TNF-alpha
      on EPC number and increased p-p38 expression levels. In order to document major
      changes of gene expression levels and gain insight into signalling pathways,
      microarray analysis was performed and a significant variation of the expression
      of 5389 genes in EPCs following antioxidant treatment was detected. Also in vivo
      evidence is provided about the positive effect of antioxidant vitamins on EPCs,
      since vitamin C and E supplementation potentiated the physical training-induced
      increase of EPC number and VEGF levels. Together, these data indicate that
      antioxidant treatment ameliorates EPC number and causes major changes of gene
      expression within these cells in vitro. Furthermore, concomitant antioxidant
      supplementation and physical training in vivo raised the levels of circulating
      EPCs and serum VEGF more than physical training alone.

PMID- 18712635
TI  - Acute mountain sickness in disability and adaptive sports: preliminary data.
AB  - Acute mountain sickness (AMS) is a frequent complication for military personnel,
      veterans, athletes, and travelers at high altitudes. Symptoms may occur in
      individuals with less cerebrospinal fluid volume and less ability to accommodate
      increased brain volume. No studies on AMS exist in individuals with neurological
      impairments. We studied 64 subjects, including active and sedentary controls and
      those with tetraplegia, paraplegia, multiple sclerosis, and traumatic brain
      injury at the 2007 National Veterans Winter Sports Clinic in Snowmass, Colorado.
      Subjects completed three Lake Louise Score surveys to quantify symptoms. We found
      a higher than expected occurrence of AMS overall (51.6%) but no differences among
      groups, and few participants sought treatment. Fatigue and weakness were common
      symptoms. High subject activity levels may explain these findings. More research
      is warranted on larger sample sizes and on preventative medications and
      treatments for AMS, especially since many military personnel with neurological
      impairments are returning to full active service.

PMID- 18712634
TI  - One lesson from arthroplasty to osseointegration in search for better fixation of
      in-bone implanted prosthesis.
AB  - Direct transcutaneous prosthetic attachment (osseointegration) consists of
      implanting directly into the residuum bone a metal pylon whose external fraction
      connects the residuum to the external prosthesis. Since the introduction of
      osseointegration about 20 years ago, the obvious challenge associated with this
      technology has been the skin-pylon interface as a source of infections. In
      comparison, the bone-device interface was considered less problematic because of
      the knowledge and experience inherited from dental implantology and total joint
      replacement (arthroplasty). Current methods of pylon fixation in osseointegration
      follow arthroplasty's paradigm of positioning the pylon's shaft inside the bone's
      medullary canal. However, adopting the medullary canal as a holding compartment
      for the pylon's shaft creates the problem of shaft loosening, which has not yet
      been solved in arthroplasty.

PMID- 18712636
TI  - Effects of assistance dogs on persons with mobility or hearing impairments: a
      pilot study.
AB  - Service dogs help persons with mobility impairments by retrieving items and
      performing other tasks. Hearing dogs alert persons with hearing impairments to
      environmental sounds. We conducted a pre-post, wait list-controlled pilot study
      to assess the impact of the dogs on the lives of recipients. Participants were
      recruited through two assistance dog training organizations and completed an
      initial questionnaire packet. The Experimental group completed another packet 6
      months after receiving a dog. The Control group completed a second packet 6
      months after the initial data collection. On average, dog recipients were very
      satisfied with their assistance dogs. Both service and hearing dog recipients
      reduced their dependence on other persons. Service dog recipients reduced hours
      of paid assistance. No other significant change occurred in various standardized
      outcome measures. Assistance dogs had a major positive impact on the lives of
      recipients. More appropriate measurement instruments are needed to capture the
      impact of these dogs.

PMID- 18712637
TI  - Distributed cognitive aid with scheduling and interactive task guidance.
AB  - A cognitive assistive technology system has been designed for use by people with
      memory and organizational impairments. This system will provide a distributed
      architecture for both scheduling assistance and task guidance, as well as
      intelligent, automatic replanning on the levels of both the schedule and
      individual tasks. A prototype of this architecture has been developed that
      focuses on interactive task guidance capabilities. Scheduling software has been
      developed but not fully integrated with the task guidance features. The system
      has been preliminarily tested through simulated trials, monitored use of the
      prototype in a clinical setting, and usability trials of the task-design
      interface with rehabilitation professionals. Participants were able to respond
      appropriately to cues provided by the system and complete prescribed tasks.

PMID- 18712638
TI  - New technique for real-time interface pressure analysis: getting more out of
      large image data sets.
AB  - Recent technological improvements have led to increasing clinical use of
      interface pressure mapping for seating pressure evaluation, which often requires
      repeated assessments. However, clinical conditions cannot be controlled as
      closely as research settings, thereby creating challenges to statistical analysis
      of data. A multistage longitudinal analysis and self-registration (LASR)
      technique is introduced that emphasizes real-time interface pressure image
      analysis in three dimensions. Suitable for use in clinical settings, LASR is
      composed of several modern statistical components, including a segmentation
      method. The robustness of our segmentation method is also shown. Application of
      LASR to analysis of data from neuromuscular electrical stimulation (NMES)
      experiments confirms that NMES improves static seating pressure distributions in
      the sacral-ischial region over time. Dynamic NMES also improves weight-shifting
      over time. These changes may reduce the risk of pressure ulcer development.

PMID- 18712639
TI  - Toward real-time detection of deep tissue injury risk in wheelchair users using
      Hertz contact theory.
AB  - This study assessed the suitability of a new portable system that is based on
      Hertz's contact theory for evaluating internal gluteal muscle stresses under the
      ischial tuberosities of wheelchair users in real-time as a risk indicator for a
      deep tissue injury. Sitting in a wheelchair was monitored and processed with the
      portable system for six control subjects and five individuals with paraplegia. We
      compared the resultant internal peak and average muscle stresses and stress
      integrals over time (stress doses) of the control subjects with those of the
      subjects with paraplegia and validated the results against previously published
      subject-specific finite element (FE) stress data for the same subjects.
      Individuals with paraplegia were characterized by peak muscle compression
      stresses (mean +/- standard deviation = 109 +/- 41 kPa) that were 2.4-fold higher
      than in control subjects (p < 0.03). A Bland-Altman comparison indicated that
      stresses recorded by the present system were in satisfactory agreement with
      previous subject-specific magnetic resonance imaging-FE analyses. We conclude
      that the present stress monitoring system has the potential to be a practical
      means for evaluating internal muscle stresses during everyday life of individuals
      with paraplegia.

PMID- 18712640
TI  - Validation of use of wireless monitors to measure levels of mobility during
      hospitalization.
AB  - Accurate methods of measuring levels of mobility during hospitalization are
      lacking. We validated the use of wireless monitors to measure three levels of
      mobility during hospitalization: (1) lying, (2) sitting, and (3) standing or
      walking. Hospitalized medical patients 65 years or older who did not have
      delirium or dementia and could walk in the 2 weeks before admission were
      eligible. Wireless monitors, which recorded average position every 20 seconds,
      were attached to the thigh and ankle of consented patients. Direct behavioral
      observation by trained observers who recorded mobility level was used as the gold
      standard. Forty-seven male patients (mean age 73.9 years), with a mean length of
      stay of 5.3 days, generated 187 two-hour direct behavioral observation periods.
      Wireless monitors were highly correlated with direct behavioral observations. The
      median kappa was 0.92 and the kappa across all observations was 0.88, indicating
      excellent agreement. This study demonstrates that wireless monitors validly
      measure mobility levels among older hospitalized patients.

PMID- 18712641
TI  - Evaluation of psychometric properties of Walking Impairment Questionnaire in
      overweight patients with osteoarthritis of knee.
AB  - This study tested the psychometric properties of the Walking Impairment
      Questionnaire (WIQ) in overweight patients with osteoarthritis (OA) of the knee.
      Internal consistency, test-retest reliability, and concurrent validity of the WIQ
      were measured. Used in a randomized clinical trial, the WIQ was one of the
      instruments completed by overweight adults with OA of the knee. A total of 105
      patients completed the WIQ. Internal consistency of the WIQ was supported in this
      population with a Cronbach alpha total score of 0.97. Test-retest reliability
      scores were not different when subjects completed the WIQ 14 days apart (p >
      0.05). The relationships were moderate between the WIQ subscales and other
      established measures, such as the 6-minute walk distance, stair climb and
      descend, and the Western Ontario and McMaster Universities (OA Index)
      questionnaire. After evaluating the psychometric properties of the WIQ, we found
      that it is a valid and reliable instrument to use in overweight patients with
      symptomatic OA of the knee.

PMID- 18712642
TI  - Influence of marker models on ankle kinematics in persons with partial foot
      amputation: an investigation using a mechanical model.
AB  - Previous studies have found that ankle dorsiflexion increases in persons with
      partial foot amputation walking shod or in "below-ankle" devices compared with
      walking barefoot. However, a logical biomechanical explanation for these findings
      has not been offered. The purpose of this project was to determine whether marker
      location might explain the exaggerated dorsiflexion reported in the literature
      and, if so, whether more accurate data could be obtained with a different marker
      set. An articulated mechanical model of the shank and partial foot residuum was
      constructed with a potentiometer located within the mechanical ankle joint. Ankle
      angles measured with the calibrated potentiometer were compared with those
      obtained with both the Helen Hayes marker set and an alternative "residual end"
      marker set. Results indicated that both marker sets provided accurate and
      comparable measures at the metatarsophalangeal and transmetatarsal levels. At the
      Lisfranc level, the Helen Hayes marker set overestimated the ankle angles,
      primarily because of deformation of the prosthetic forefoot. These results
      confirm that the choice of kinematic model does influence measurements of ankle
      motion in persons with partial foot amputation and that the residual end marker
      set more accurately measures ankle motion at the Lisfranc level.

PMID- 18712643
TI  - Ambulation monitoring of transtibial amputation subjects with patient activity
      monitor versus pedometer.
AB  - Our study aimed to compare the accuracy of step count and ambulation distance
      determined with the Yamax Digi-Walker SW-700 pedometer (DW) and the Ossur patient
      activity monitor (PAM) in 20 transtibial amputation subjects who were functioning
      at the K3 Medicare Functional Classification Level. Subjects completed four
      simulated household tasks in an apartment setup and a gymnasium walking course
      designed to simulate outdoor walking without the presence of environmental
      barriers or varied terrain. The mean step count accuracy of the DW and the PAM
      was equivalent for both the household activity (75.3% vs 70.6%) and the walking
      course (93.8% vs 94.0%). The mean distance measurement accuracy was better with
      the DW than with the PAM (household activity: 72.8% vs 0%, walking course: 92.5%
      vs 86.3%; p < 0.05). With acceptable step count accuracy, both devices are
      appropriate for assessing relatively continuous ambulation. The DW may be
      preferred for its more accurate distance measurements. Neither device is ideal
      for monitoring in-home ambulation.

PMID- 18712644
TI  - Electroacupuncture may help motor recovery in chronic stroke survivors: a pilot
      study.
AB  - Past studies have suggested that acupuncture may reduce spasticity in stroke
      survivors. We do not know, however, whether acupuncture may enhance the effect of
      strength training on motor function. This study compared upper-limb motor
      functional improvement in chronic stroke survivors who received a combination of
      acupuncture and strength training with that of subjects who received strength
      training alone. A total of 10 chronic stroke patients with moderate or severe
      wrist muscle spasticity were recruited for this study. The study used a crossover
      design with a random order of either combined electroacupuncture and strength
      training or strength training alone. Each subject received one of the two types
      of treatment twice a week for the first 6 weeks and switched to the other for
      another 6 weeks. Quantitative measurements of wrist spasticity, active wrist
      extension range of motion, isometric wrist strength, and clinical evaluation with
      Fugl-Meyer (FM) upper-limb motor scores were conducted before and after either
      treatment. After the combined treatment, the quantitative spasticity level,
      active wrist extension range of motion (increased by a mean of 16.3 degrees), and
      FM upper-limb motor score (increased by a mean of 4.9 points) changed
      significantly (p < 0.01) but no significant changes were noted in isometric wrist
      strength. The strength training alone resulted in no significant changes to any
      measured variable. The results of the current study indicate that the combined
      acupuncture and strength training treatment reduced muscle spasticity and may
      have improved motor function for chronic stroke survivors with moderate or severe
      muscle spasticity.

PMID- 18712645
TI  - Prevalence and characteristics of dual sensory impairment (hearing and vision) in
      a veteran population.
AB  - With the increasing aging population, the number of veterans presenting with dual
      sensory impairment (DSI) (vision and hearing impairments) will increase. This
      study determined the prevalence and clinical characteristics of DSI in a veteran
      population receiving healthcare from the Department of Veterans Affairs (VA). A
      retrospective review was conducted on 400 charts randomly selected from a
      database of 1,472 unique veterans enrolled in the audiology and optometry
      outpatient clinics during a 1-year period. Depending on definition criteria,
      hearing impairment prevalence was 41.6% to 74.6%, vision impairment/blindness
      prevalence was 7.4%, and DSI prevalence was 5.0% to 7.4%. The vision
      impairment/blindness prevalence governed the DSI prevalence. By age, DSI
      prevalence ranged from 0% (among veterans <65 years) to >20% (among veterans 85+
      years). The complexities encountered in defining DSI are discussed and
      suggestions are made for determining standardized definitions. More research is
      needed to determine the unique characteristics of individuals with DSI and their
      impact on VA resources.

PMID- 18712646
TI  - Accuracy of uniaxial accelerometer in chronic obstructive pulmonary disease.
AB  - Wearable sensors have been developed and used in nondisabled adults. Little is
      known about their accuracy in patients with chronic disease. We tested the
      ActiHealth accelerometer, which measures step counts, in subjects with chronic
      obstructive pulmonary disease (COPD). We determined the intra- and interdevice
      coefficients of variation (CVs). We assessed the accuracy of the device in 15
      nondisabled males and 46 subjects with COPD. Accuracy was defined as percent step
      capture, (device step count divided by manual step count) times 100. Predictors
      of percent step capture were identified using linear regression methods. The
      accelerometer has an intradevice CV ranging from 0.008 to 0.025 and an
      interdevice CV of 0.64. In nondisabled males, median percent step capture was 96%
      (interquartile range 81%-98%). In subjects with COPD, median percent step capture
      was 86% (interquartile range 72%-96%). Usual walking speed was the most important
      predictor of percent step capture (p = 0.004). The ActiHealth accelerometer has
      acceptable intra- and interdevice CVs. It is highly accurate in nondisabled
      subjects. The accuracy declines in subjects with COPD based on walking speed.
      Prior to using the ActiHealth accelerometer, researchers and clinicians should
      assess walking speed and percent step capture in each subject.

PMID- 18712647
TI  - Reliability and validity of World Health Organization Quality of Life-100 in
      homeless substance-dependent veteran population.
AB  - The number of homeless individuals and specifically homeless veterans is
      increasing. Accurate assessment of quality of life is an important need in
      working with this population because of the myriad problems encountered. However,
      the reliability and validity of quality-of-life instruments have not been
      assessed in this population. This study evaluated the psychometric properties of
      the U.S. version of the World Health Organization Quality of Life-100 in a
      homeless veteran population. Results found adequate internal consistency for all
      domain and most facet scores, while test-retest stability varied for the facet
      scores. We confirmed validity by using subsamples with physical, emotional, and
      social problems and by comparing scores from populations that returned to the
      community with employment and housing. Limitations and directions for future
      study are discussed.

PMID- 18712648
TI  - Effective methods of pelvic plexus nerve and bladder stimulation in anesthetized
      animal model.
AB  - Urinary retention is a serious urological problem associated with spinal cord
      injuries (SCIs) and other pelvic disorders. Effective methods of pelvic nerve
      stimulation were investigated for this problem. Following anesthesia in five
      dogs, the bladder was surgically exposed. Bladder and anal sphincter pressures
      were recorded. Testing was first conducted with probe electrodes. Barb electrodes
      were then implanted with a needle near the pelvic plexus nerves and the bladder
      wall. We tested different electrode arrangements and stimulating parameters to
      induce bladder contractions without skeletal muscle stimulation. The pelvic
      plexus nerves near the bladder were identified, and the barb electrodes were
      effectively implanted. Stimulation with bipolar and bilateral electrodes induced
      pressures over 30 cmH(2)O without skeletal muscle activation. Common stimulation
      parameters were 40 pps, 400 microseconds pulse duration, and 15 to 25 mA
      stimulating current applied for 3 s. Effective electrode implantation methods
      were shown. Also identified were electrode arrangements and stimulating
      parameters that induced strong bladder contractions without skeletal muscle
      activation. However, voiding studies were not conducted. Further studies with
      barb electrodes are warranted, and these methods may have applications for
      bladder stimulation following SCI.

PMID- 18712650
TI  - [Staged requirements for therapy of keratoconus].

PMID- 18712649
TI  - A 24-hour feasibility study of intraurethral valved catheter for bladder
      management in males with spinal cord injury.
AB  - This feasibility study was conducted to evaluate design features of the novel
      intraurethral valved catheter, Surinate (Urovalve, Inc; Newark, New Jersey). The
      device extends from the bladder neck to just beyond the external sphincter and
      contains a valve that can be activated by an external magnet for bladder
      emptying. Five patients were recruited from the Edward Hines Jr Department of
      Veterans Affairs Hospital spinal cord injury population. We conducted cystometry
      and cystoscopy to evaluate the lower urinary tract. Then, the device was inserted
      for 24 hours with careful monitoring. The catheter was removed from the first
      patient because he developed autonomic dysreflexia during implantation. The next
      four patients used the catheter overnight and tolerated it well: one with
      independent use and two with increased abdominal pressure. Emptying time was 208
      +/- 99 s, residual was 42 +/- 33 mL, and the first-stream flow rate was 1.8 +/-
      0.7 mL/s. The safety tether was used in three patients because the extraction
      device did not work. Results showed effective implantation and stability of the
      device in the urethra. However, objectives for use and extraction were not met.
      This feasibility study provided important information that will help guide design
      improvements for the intraurethral valved catheter.

PMID- 18712651
TI  - [Intraorbital tumours of the peripheral nervous system].
AB  - In neoplastic processes in the orbital area, a not significant part of these new
      entities is caused by tumours of the peripheral nervous system. Due to a
      clinically similar behaviour and radiological features also being similar, these
      tumours sometimes cause differential diagnostic difficulties. Our experience with
      these tumours shows that they do not have a uniform symptom complex. Exophthalmus
      and displacement of the globe are the most visible symptoms besides pain,
      motility disturbances, reduced visus and double images. Clinical imaging allows
      the exact localisation of the tumour and makes it easier to choose the best
      surgical method. However, imaging does not allow the exact assessment of the
      entity or enable a decision to be made about the possible malignancy of the
      tumour. Therefore, a representative biopsy and a histopathological examination
      are essential. Then, a complete tumour resection should be performed using the
      most careful incision possible to avoid postoperative complications.

PMID- 18712652
TI  - [Eye lid tumours--clinical features, diagnosis and surgical treatment].
AB  - PURPOSE: Various procedures for surgery in eye lid tumours are described. The aim
      of lid reconstruction is restoration of function, comfort and cosmesis. METHODS:
      This article presents typical clinical features of and the commonly used surgical
      procedures for eye lid tumors in relation to lid function and characteristics of
      lid anatomy. RESULTS: Surgical procedures depend on localisation, extension and
      histology of the eye lid tumour. A defect that includes the medial or lateral
      canthus is a special surgical problem. If either canthal tendon has been
      disrupted it must be reconstructed to have adequate medial and lateral support to
      prevent the lid from drooping. CONCLUSIONS: Eye lid tumours can be observed or
      treated (medication or surgery). It is possible to reconstruct lid defects even
      when they are of considerable size with excellent functional and cosmetic
      results.

PMID- 18712653
TI  - [Non-Pharmacological Interventional Perspectives in AMD].
AB  - Transplantation and translocation surgery for the treatment of AMD has been
      evaluated for over 25 years. More recently injections of inhibitors of
      vascularisation have been used with some success. Inhibitors of
      neovascularisation result in the recovery of vision in about 30% of patients;
      however, we do not understand what criteria can be used to select patients who
      will respond to or will not respond to treatment with antivascularisation
      treatment. We have to assume that successful antivascularisation treatment will
      require first that the retinal pigment epithelial cells be present and functional
      and second that the photoreceptor cells should not be degenerated. We then
      hypothesise that if either of these two parameters are not present, antivascular
      treatment will not result in vision recovery and we must then consider surgical
      intervention. Surgical intervention for macular degeneration encompasses
      procedures from simple membrane extraction to macular rotation to cell
      transplantation or a combination of these procedures, however these procedures
      must take into account that vision recovery cannot be achieved without
      reconstruction of the retina-choroid complex. Since in AMD degeneration of the
      retinal pigment epithelial cells and vascular membranes removal results in damage
      to the basal lamina and possibly deeper layers of Bruch's membrane, it will be
      necessary to reconstruct these damaged structures. In fact, transplantation of
      RPE cells or IPE cells has not resulted in any significant improvement in vision
      in AMD patients. Long-term follow-up of AMD patients following macular rotation
      surgery has shown that significant visual recovery is not maintained in most
      patients. Of the many approaches that could be used to reconstruct the damaged
      basal lamina and Bruch's membrane the most promising would be the introduction of
      a monolayer of pigment cells on a "natural" biodegradable substratum. A natural
      substratum consisting of extracellular matrix proteins would allow the pigment
      cells to retain their differentiated characteristics and functions, including the
      degradation the substratum and production of the normal components of the basal
      lamina and Bruch's membrane. In addition, the cells introduced as a monolayer can
      be engineered to carry specific genes to aid in the restructuring of the retina
      choroid complex, such as growth factors and inhibitors of vascularisation.

PMID- 18712654
TI  - [Potential endogenous immunological self-protection of uveal melanoma by
      indoleamine 2,3-dioxygenase].
AB  - BACKGROUND: Uveal melanomas are the most common intraocular tumours in the adult.
      Although they represent less than 1% of all tumour cases, uveal melanomas are
      considerd to be rather aggressive due to early hepatic metastases. Indoleamine
      2,3-dioxygenase (IDO) is the principle enzyme in the degradation of the essential
      amino acid L-tryptophan to L-kynurenine. MATERIALS AND METHODS: In this study,
      the L-kynurenine production of six uveal melanoma cell lines was examined and
      immunohistochemistry performed for detection of IDO expression within uveal
      melanomas. RESULTS: In all the examined cell lines, a basal degradation of
      tryptophan to L-kynurenine was detectable. Supplementation with interferon-gamma
      could up-regulate this basal L-kynurenine production. The expression of IDO using
      immunohistochemistry was demonstrated within all examined tumours. CONCLUSIONS:
      The expression of IDO within the tumours may shed light on an important adaptive
      mechanism which allows the melanoma cells to escape T-cell-dependent
      immunosurveillance as soon as these cells metastise and enter non-immunologically
      privileged tissue. As competitive inhibition of IDO by 1-methyl-tryptophan is
      possible, a new therapeutic pathway might be available.

PMID- 18712655
TI  - [Autogenous tarsus transplant as spacer for treatment of lower lid retraction in
      Grave's disease].
AB  - BACKGROUND: Lower lid retraction in dysthyroid orbitopathy is of less functional
      concern than optic neuropathy or diplopia in central positions of gaze. However,
      it may lead to incomplete lid closure resulting in corneal exposure. Patients
      often suffer from aesthetic impairment. PATIENTS AND METHODS: A retrospective
      analysis of 13 consecutive patients treated for lower lid retraction due to
      Grave's Disease between 2005 and 2007 was undertaken. In spite of regular
      ophthalmological examinations, specific attention was directed to measurement of
      the lid fissure width and scleral show for quantification of lower lid
      retraction. OPERATION: The lower lid is everted and the conjunctiva is opened
      horizontally underneath the tarsal edge. Lower lid retractors are disinserted and
      dissected until the lower lid might be elevated in symmetry to the fellow eye.
      This procedure is continued until 1 mm overcorrection is gained. A free tarsal
      transplant is harvested from the ipsilateral upper lid tarsus. At least 4 mm
      vertical tarsus have to be left. Tarsus is sutured with absorbable material.
      RESULTS: In the 13 patients operated upon (9 women, 4 men) aged 23 - 67 years,
      scleral show was preoperative 2.7 mm (mean) and postoperative 0.1 mm. Lid fissure
      width was preoperative 13 mm (10 - 16 mm) and immediately postoperative 10.3 mm
      (7 - 13). 6 months postoperative the lid-elevating effect was reduced by 0.5 mm
      in maximum in the 9 patients available for control. The lid closure deficit,
      which was present in 7 patients before, could be corrected completely in 5 and
      diminished to 1 mm in 2 patients. CONCLUSIONS: Using this particular technique,
      functional and aesthetical satisfying results are obtained. The main advantages
      are renunciation of allogen, xenogeny or synthetic material with its possible
      risks of slow-virus infection and/or extrusion. Further studies are necessary to
      evaluate long-term results.

PMID- 18712656
TI  - [Optical coherence tomography findings in hemodialysis patients].
AB  - BACKGROUND: The aim of the present prospective study was to compare retinal
      thickness between normal healthy subjects and chronic renal failure patients
      treated with maintenance hemodialysis (HD) as well as to determine whether there
      was any correlation between age and duration of HD treatment. PATIENTS AND
      METHODS: A total of 24 eyes of 12 HD patients and 32 eyes of 16 controls
      underwent optical coherence tomographic scanning (OCT) in the central disc of
      6000 mum in diameter. RESULTS: The mean retinal thickness was measured in the
      inner temporal, superior, nasal and inferior quadrants. There was a highly
      significant difference in the inner quadrants between controls and HD patients (p
      < 0.005). The mean retinal thickness was also measured in all outer quadrants.
      The differences between HD patients and controls were highly significant (p <
      0.005). The average reduction in retinal thickness in HD patients compared to the
      controls in the inner quadrants was 7.9% or 22 microm (279.0 in controls, 257.0
      in HD patients) and 7.3% or 17.7 microm in the outer quadrants (244.5 in
      controls, 226.8 in HD patients). The average reduction in all quadrants was 7.7%
      or 20.1 microm (262 in controls, 241.9 in HD patients). The differences between
      HD patients and controls were highly significant in all quadrants (p < 0.001). No
      differences in foveal thickness between controls and HD patients were found. The
      reduction of retinal thickness was correlated with the age of HD patients, but
      not with the duration of HD treatment. CONCLUSION: OCT revealed a significant
      reduction of retinal thickness in HD patients. The reduction was significant in
      all quadrants and was correlated to the age of HD patients. No differences in
      foveal retinal thickness were found.

PMID- 18712657
TI  - [Comparison of frequency doubling technology perimetry and achromatic standard
      automated perimetry in patients with migraine without aura and controls].
AB  - BACKGROUND: The frequency doubling technology perimetry predominantly tests the
      magnocellular visual pathway (M-cells) whereas the achromatic standard automated
      perimetry examines magno- and parvocellular ganglion cells. The aim of this study
      was to investigate whether patients with migraine without aura are conspicuous in
      these perimeters. MATERIALS AND METHODS: Thirty-two patients with migraine
      without aura (f:m = 2:30, mean age 40.4 +/- 11.34 years) were compared with
      nineteen controls (f:m = 1:18, mean age 40.15 +/- 12.5 years). Subjects with
      systemic health problems or ocular diseases were excluded from the study. Beside
      the ophthalmological examinations (visual acuity, refraction, intraocular
      pressure, slit lamp and fundus examination) quantitative analysis of visual field
      by Octopus 1 - 2 - 3 perimeter and Humphrey frequency doubling technology
      perimeter (FDT) were performed. Different parameters (mean deviation [MD] and
      pattern standard deviation [PSD]) were statistically compared using non
      parametric tests. RESULTS: The clinical ophthalmological examinations were
      inconspicuous in all migraine sufferers and controls. Statistical analysis showed
      no significant difference of MD and PSD between the patients with migraine and
      controls in the frequency doubling perimetry. However, there was a significant
      difference of MD using the achromatic standard perimetry in migraine sufferers in
      comparison to the controls (migraine - right eye MD 0.4 +/- 1.33 dB, migraine -
      left eye MD 0.2 +/- 1.47 dB, controls-right eye MD -1.4 +/- 0.76, controls - left
      eye -1.4 +/- 0.84; Mann-Whitney U test: p < 0.001 with Bonferoni-Holms
      correction). CONCLUSION: In migraine sufferers without aura we found a reduction
      of contrast sensitivity in the achromatic standard perimetry but not in the
      frequency doubling technology perimetry. This can be indicative of a stronger
      involvement of the parvocellular pathway in migraine without aura patients. These
      results should be take into consideration in further perimetric examinations.

PMID- 18712658
TI  - [Combined squamous cell carcinoma and malignant melanoma of the eyelid].
AB  - We present a case report of co-existent components of squamous cell carcinoma and
      malignant melanoma within a solid eyelid tumour in a 74-year-old male. The
      particular composite of these two malignancies in ocular adnexa is to the best of
      our knowledge reported for the first time. The histological findings exhibited a
      solid anterior lid tumour infiltrating the skin and surrounding conjunctiva, as
      well as the orbicular muscles. The hyper- and parakeratotic keratin-rich squamous
      cell carcinoma was cytokeratin AE1/AE3 positive, had a slight atypia but an
      obvious invasion in the depth. Between the squamous cell carcinoma cells were
      islands of HMB45 and Melan-A positive melanoma cells with slight pigmentation,
      which demonstrated not only subcutaneous but also intraepithelial invasion.

PMID- 18712659
TI  - [Re-re-relapse of a MALT lymphoma of the conjunctiva].
AB  - BACKGROUND: The MALT lymphoma (mucosa-associated lymphoid-like tissue lymphomas)
      is a rare entity and belongs to the low-grade non-Hodgkin (NHL) lymphomas. In 8 %
      of cases it arises in the conjunctiva. In some cases a MALT lymphoma of the
      conjunctiva is misdiagnosed as chronic conjunctivitis. Mostly a MALT lymphoma of
      the conjunctiva can be cured by radiation and has a good prognosis. CASE REPORT:
      A 61-year-old female presented to our hospital because of alteration of the
      conjunctiva and worsening of her general condition. Symptoms were fatigue,
      lassitude, night sweat, loss of appetite and gastrointestinal problems. The
      medical history revealed treatment for a MALT lymphoma 4 years previously and a
      relapse 3 years previously. Both were resected totally. Staging at those times
      gave no hint for metastases. The ophthalmological examination showed an adherent
      prominence with conjunctival injection of the right eye at 10 - 11 o'clock. It
      corresponded to the localisation of the primary tumour in 2002 and the relapse in
      2003. Slit lamp and fundoscopic examinations only revealed a cataracta incipiens.
      CLINICAL COURSE: To confirm the diagnosis a biopsy was done. The histological
      examination demonstrated a relapse of the MALT lymphoma. Staging gave no hint for
      metastases. The patient was referred to the oncological unit for chemotherapy (R
      CHOP regime). CONCLUSION: This case shows that a relapse of the MALT lymphoma may
      arise although the previous tumour and its relapse were resected totally. In
      patients with tumours in their medical history suffering from unspecific
      discomfort, a biopsy should may be be considered despite the lack of apparent
      macroscopic findings.

PMID- 18712660
TI  - [Abnormal head turn in a patient with Brown's syndrome].
AB  - BACKGROUND: We report on an eight-year-old boy, who was presented in our clinic
      because of head turn. The cause of the tortecollis (ocular or general) in this
      case was and still cannot be explained. Only by applying extensive prism
      adaptation tests it was possible to prove the ocular character of the head turn.
      CASE REPORT: An eight-year-old boy with Brown's syndrome was referred to us
      because of a head tilt to the left side. Six months previously surgery on the M.
      obl. superior of the right eye was performed in another clinic. No improvement of
      the head tilt could be observed after the operation. In addition, an exotropia
      became decompensated. Under a 3-day occlusion of one eye, no change of the head
      turn and the squint could be measured. No other cause of the head turn could be
      found by an orthopaedist and a paediatrist. Under a prism of 20 cm/m basis in and
      10 cm/m basis against the positive vertical deviation, the head tilt decreased,
      so that we decided to do a second surgery. The head tilting had not resumed at
      one year after the surgery. CONCLUSIONS: Although the initial diagnostic findings
      ruled out an ocular cause, it was possible to lessen the head tilting with the
      aid of the prism adaptation test. This case study emphasises the usefulness of a
      prism adaptation test of several days duration in order to validate an ocular
      cause of head turn and to determine an adequate indication for surgery.

PMID- 18712661
TI  - [Asteroid hyalosis within an epiretinal membrane].
AB  - CASE REPORT: In May 2007 an 80-year-old man with a known proliferative diabetic
      retinopathy presented in our outpatient department with a decrease in visual
      acuity of his right eye. There was a thick asteroid hyalosis preventing fundus
      examination. Sonographically, there were vitreoretinal tractions requiring a
      vitrectomy. During surgery an epipapillary membrane was removed. RESULTS:
      Microscopically round amorphous bodies were conspicuous which were slightly
      basophilic in the H&E stain. The amorphous bodies were strongly positive in the
      periodic acid-Schiff staining. They were embedded in a fibrovascular stroma and
      partly surrounded by inflammatory cells with numerous giant cells of foreign body
      reaction. CONCLUSION: Asteroid hyalosis is a common degenerative disorder in the
      vitreous body. The aetiology and the pathogenesis of the asteroid bodies are not
      yet fully understood. An association of asteroid hyalosis with systemic diseases
      like diabetes mellitus, arterial hypertension, hyperlidpidaemia and
      atherosclerotic vasculopathy is postulated. Normally, therapy for an asymptomatic
      asteroid hyalosis is not necessary. The tractive proliferative diabetic
      retinopathy in our patient did require surgery. The incorporation of hyaloid
      bodies into an epiretinal membrane with the induction of a foreign body reaction
      is unusual.

PMID- 18712662
TI  - [The enamelled golden spectacles of Archduke Ferdinand II from Austria-Tyrol].

PMID- 18712663
TI  - [Does the neurogenesis in the adult brain show the way into the future?].

PMID- 18712664
TI  - [Neurogenesis in the adult brain: from bench to bedside?].
AB  - Two regions of the mammalian brain maintain the capability to generate new
      neurons throughout lifetime: Neuronal stem- and precursor cells proliferate in
      the subgranulare zone (SGZ) of the dentate gyrus in the hippocampus and in the
      subventricular zone (SVZ) of the lateral ventricles to give rise to new neurons
      that are functionally integrated into the neural network. The functional
      relevance of adult neurogenesis under physiological conditions on one hand, and
      the newly discovered potentiality of cellular regeneration in the diseased brain
      on the other hand, arouse the interest of fundamental and clinical
      neuroscientists. There is growing evidence that impaired adult neurogenesis is
      linked to the etiology of neuropsychiatric disorders (such as depression or
      Alzheimer's disease), as well as that the neurogenic potential may be used for
      the treatment of neurodegenerative diseases (such as Parkinson's disease or
      stroke). This review summarizes the neurobiological bases of adult neurogenesis
      in their relevance for the future trend of novel therapeutic strategies.

PMID- 18712665
TI  - [Psychotherapeutic treatment concepts of personality disorders in patients with
      childhood traumatization].
AB  - The psychotherapeutic treatment of personality disorders in patients with
      childhood traumatization is still a major challenge. The broad range of clinical
      problems includes disturbed emotion regulation, reduced mentalization function,
      impaired integration of personality, maladaptive patterns of behavior and a high
      degree of comorbidity. A variety of treatment concepts of psychodynamic,
      cognitive-behavioral, and other origin have been developed to treat this patient
      population. The aim of this paper is to identifiy those concepts whose
      effectiveness has been sufficienty demonstrated by controlled studies. The
      concepts will be briefly described and evaluated with regard to their utility in
      focusing specific clinical problem areas. While a variety of treatment approaches
      has been developed for this condition, only a limited number of concepts of
      cognitive-behavioral and psychodynamic origin show up with sufficient evidence in
      terms of controlled studies. Among the cognitive-behaviorally oriented concepts
      are: Dialectical-behavioral Psychotherapy (Linehan), Affect Management Training
      (e. g. Cloitre), and Schema Therapy (Young). The psychodynamic concepts with
      evidence of effectiveness are: Tranference-focused Psychotherapy
      (Kernberg/Clarkin), Psychodynamic-interactional and Structure-related
      Psychotherapy (Heigl-Evers & Heigl, Rudolf), Mentalization-based Treatment
      (Bateman & Fonagy), and Psychodynamically Oriented Trauma Therapy (Reddemann,
      Sachsse). However, a critical discussion of these concepts reveals that, because
      of the heterogeneity of the patient population, none of these concepts is able to
      cover all types of clinical problems presented by the patients.

PMID- 18712666
TI  - [Mental time travel - the neurocognitive basis of future thinking].
AB  - The ability to travel in time mentally, i. e. the re-experiencing of personal
      past events as well as the ability to mentally simulate potential future events,
      forms part of the "episodic memory" concept. Evidence for the notion that
      episodic memory and episodic future thinking share a common neural basis stems
      from different lines of research, namely functional neuroimaging, assessment of
      clinical groups, behavioral investigations of the phenomenological
      characteristics of mental time travel, and developmental research. The present
      article summarises the evidence from these lines of research which indicate a
      common neural network underlying episodic memory and episodic future thinking,
      consisting of medial prefrontal, medial temporal, medial parietal, lateral
      parieto-occipital, as well as lateral temporal regions. Both abilities, episodic
      memory and future thinking, seem to develop around the age of four years, feature
      similar phenomenological characteristics, and are impaired to a similar extent by
      brain lesions and brain dysfunction. These findings yielded different hypotheses
      concerning the function and evolutional significance of the mental time travel
      network, which will also be addressed.

PMID- 18712667
TI  - [Acute therapy of stroke].

PMID- 18712668
TI  - Hyper-methylation of RIZ1 tumor suppressor gene is involved in the early
      tumorigenesis of hepatocellular carcinoma.
AB  - The retinoblastoma protein-interacting zinc finger gene RIZ1 is a putative tumor
      suppressor gene, and the inactivation of the RIZ1 is frequently found in tumors
      through a loss of mRNA expression. In order to understand the role of RIZ1
      inactivation in the tumorigenesis of hepatocellular carcinoma (HCC), we detected
      the RIZ1 promoter methylation status in 39 HCCs using a methylation specific PCR
      (MSP) method, and carried out LOH study with marker P704. We also assessed the
      associations between the methylation status and clinicopathological parameters,
      tumor size, tumor differentiation, and fractional allelic loss (FAL). The results
      showed that the RIZ1 promoter methylated both in advanced tumors (>3 cm), (18/31,
      58.0%) and in early tumors (<3 cm), (4/8, 50.0%). There were 54.6% (12/22) tumors
      with hyper-methylation in the low FAL group and 45.5% (10/22) in the high FAL
      group. Moreover, the DNA methylation of the RIZ1 promoter was found not only in
      the poorly differentiated tumors (12/22, 54.6%), but also in the well
      differentiated tumors (10/22, 45.5%). Among the 22 HCCs (22/39, 56.4%) that
      showed hyper-methylation at the RIZ1 promoter region, 3 cases showed biallelic
      methylation. Interestingly, one case showed hyper-methylation on one allele and a
      loss of heterozygosity (LOH) on the other allele. In other words, 4 HCCs showed
      the biallelic inactivation of the RIZ1. These results suggest that the
      inactivation of the RIZ1 by DNA methylation at its promoter region is involved in
      the tumorigenesis of HCC, particularly in the early stage of disease.

PMID- 18712669
TI  - Treatment with tacrolimus enhances alveolar bone formation and decreases
      osteoclast number in the maxillae: a histomorphometric and ultrastructural study
      in rats.
AB  - Recent studies have suggested that tacrolimus monotherapy is a beneficial
      therapeutic alternative for the normalization of cyclosporin-induced bone loss in
      animal models and humans. The mechanism accounting for this action is unclear at
      present. In the present study, we attempted to determine the effect of tacrolimus
      monotherapy on alveolar bone using histological, histomorphometric and
      transmission electron microscopy (TEM). Groups of rats (n=10 each) were treated
      with either tacrolimus (1mg/kg/day, s.c.) or drug vehicle for 60 days. Fragments
      containing maxillary molars were processed for light microscopy to investigate
      the alveolar bone volume, trabecular separation, number of osteoclasts and
      osteoblasts, and transmission electron microscopy to investigate their
      ultrastructural basic phenotype. Treatment with tacrolimus monotherapy during 60
      days may induce increases in alveolar bone volume (BV/TV,%; P<0.05) and a non
      significant decrease in trabecular separation (Tb.Sp,mm; P>0.05), represented by
      a decrease in osteoclast number (N.Oc/BS; P<0.05) and maintenance of osteoblast
      number (N.Ob/BS; P>0.05). Osteoblasts were often observed as a continuous layer
      of active cells on the bone surface. Osteoclasts appeared to be detached from the
      resorbed bone surface, which was often filled by active osteoblasts and collagen
      rich matrix. Moreover, osteoclasts in the treated group were frequently observed
      as inactive cells (without ruffled border, clear zone and detached from the bone
      surface). Within the limits of the present study, we conclude that tacrolimus
      leads to an increase in alveolar bone formation, which probably exerts action on
      osteoclasts. Tacrolimus could, therefore, play a crucial role in the control of
      both early osteoclast differentiations from precursors, as well as in functional
      activation.

PMID- 18712670
TI  - Primary perivascular epithelioid cell tumor of the liver not related to hepatic
      ligaments: hepatic PEComa as an emerging entity.
AB  - Primary perivascular epithelioid cell tumor (PEComa) of the liver is a very rare
      example of an emerging family of hepatic PEC tumors. Only few cases have been
      described so far. We report the case of a large but benign hepatic PEComa in a 53
      year-old man without signs of tuberous sclerosis. In contrast to recently
      described PEC-derived liver tumors in children and young adults, this neoplasm
      was not related to the hepatic ligaments but had developed deeply within the
      liver substance. The neoplastic cells displayed the complete phenotype typical
      for PEComas, i.e. reactivity for several melanoma markers and for smooth muscle
      actin. The unique relationship of myoid tumor cells to the adventitia of blood
      vessels prompted us, in comparison with published findings obtained with
      angiomyolipomas, to comment on the possible origin of the still enigmatic
      perivascular epithelioid cells.

PMID- 18712671
TI  - Reg I protein in healthy and seminoma human testis.
AB  - Regenerating gene (Reg), encodes a secretory protein with growth and
      differentiation stimulating effects mostly in digestive tissues. Overexpression
      of Reg proteins and specifically of Reg I, one member of the Reg family, is
      associated with several human diseases and cancers. In the present study we
      analyzed the expression of Reg I in normal rodent and human testes where germ
      cells normally proliferate and differentiate into spermatozoa, and in seminoma
      testis, the most common cancer of young men. Western blot analyses demonstrated
      the presence of a specific band at 19 kDa in human and rodent testis extracts.
      Immunofluorescence and deconvolution microscopy demonstrated that Reg I was
      present within the seminiferous tubules in both Sertoli and germ cells. By using
      a Sertoli cell line we demonstrated that Reg I was localized at the plasma
      membrane even in the absence of contact between neighboring cells and appeared
      before the tight junction associated protein ZO-1 was revealed at this location.
      Reg I was strongly expressed in human seminoma testis tissue and in a human tumor
      germ cell line where the immunoreactive signal was mainly detected at the plasma
      membrane level. These data showing for the first time the weak presence of Reg I
      in the normal testis and its strong expression in the testis cancer suggest a
      potential role of Reg I in normal and neoplastic germ cell proliferation.

PMID- 18712672
TI  - Loss of a reporter gene for green fluorescent protein during tumor progression
      suggests the recruitment of host cells in rats with experimentally induced colon
      cancer.
AB  - The interactions between a host's normal cells and tumor cells appear to be of
      significant importance during the development of tumors. In the present study, we
      examined this issue using a cancer model in vivo in which tumor cells were tagged
      with a reporter gene for green fluorescent protein (GFP). We used a model of
      colon cancer in immunocompetent rats, which were given a subcutaneous injection
      of tumor cells that had been transfected with a gene for GFP. We found that the
      number of fluorescent cells decreased with the progression of the primary tumors
      and that lymph node and lung metastases were never macroscopically fluorescent.
      No GFP-encoding sequences were detected by PCR in many of the long-term primary
      tumors, in most lymph node metastases (86%) and in all lung metastases, whereas
      the detection of mutated k-ras, which identified such cells as tumor cells, was
      always positive. To explain these findings, we present a brief review of the
      literature and postulate that tumor growth did not occur exclusively as a result
      of the division of the injected cells, but also involved recruitment of host
      cells.

PMID- 18712673
TI  - Expression profile of metastasis-related genes in invasive oral cancers.
AB  - We used suppression subtractive hybridization (SSH) and oligonucleotide
      microarray to differentiate expression profiles of metastasis-related genes and
      to evaluate their clinical significance in patients with invasive oral cancer
      (OCa). Overexpression of the specific genes was confirmed by reverse
      transcription-PCR (RT-PCR). Cells expressing the gene were identified by
      immunohistochemistry in pathology specimens. Clinical correlation and
      significance were analyzed statistically. Using these methods, we detected
      increased expressions of MMP-1, -3, -7, -9, -10 and interleukin (IL)-8 in
      invasive OCa. Moreover, our data showed that overexpressions of MMP-1, -3, -7, 
      10 and IL-8 were associated with reduced survival.

PMID- 18712674
TI  - Immunophenotyping of acute lymphoblastic leukemia using immunohistochemistry in
      bone marrow biopsy specimens.
AB  - Flow cytometry is the preferred method of diagnosing and immunophenotyping acute
      lymphoblastic leukemia (ALL). However, there are situations in which
      immunohistochemical staining (IH) of bone marrow trephine biopsy specimens can be
      used to provide immunophenotypic information. To evaluate the use of IH and to
      confirm its value in diagnosing and typing of ALL, we studied 50 cases of denovo
      ALL that were previously classified into pre B, T and B by morphologic,
      cytochemical and FC methods. Paraffin embedded bone marrow trephine biopsies
      sections were stained using a panel of antibodies,namely, myeloperoxidase (MPO),
      terminal deoxynucleotidyl transferase (TdT), CD10, CD20, CD79a, CD3. The cases
      included 37 pre BALL, 10 T ALL and 3 mature BALL. TdT was the most commonly
      expressed antibody and was positive in 41 of 50 cases of ALL (82%) and in 95% of
      pre B ALL cases. CD79a and CD10 were positive in 68% and 65% of pre B ALL cases,
      respectively. CD79a showed similar positivity in B ALL cases (66%). CD 20 was
      positive in 66% of mature B ALL cases but less positive in pre B ALL (22%). CD3
      was positive in 70% of T ALL cases and negative in other ALL subtypes. All of the
      cases were negative for MPO. Diagnosis and immunophenotyping of acute
      lymphoblastic leukemia is possible using immunohistochemical staining of bone
      marrow trephine biopsies.

PMID- 18712675
TI  - The histopathology of a human mesenchymal stem cell experimental tumor model:
      support for an hMSC origin for Ewing's sarcoma?
AB  - Sarcomas display varied degrees of karyotypic abnormality, vascularity and
      mesenchymal differentiation. We have reported that a strain of telomerized adult
      human bone marrow mesenchymal stem cells (hMSC-TERT20) spontaneously evolved a
      tumorigenic phenotype after long-term continuous culture. We asked to what extent
      our hMSC-TERT20 derived tumors reflected events found in human sarcomas using
      routine histopathological procedures. Early versus late passage hMSC-TERT20
      cultures persistently expressed mesenchymal lineage proteins e.g. CD105, CD44,
      CD99 and vimentin. However, late passage cultures, showed increased
      immunohistochemical staining for CyclinD1 and p21WAF1/Cip1, whereas p27Kip1
      staining was reduced. Notably, spectral karyotyping showed that tumorigenic hMSC
      TERT20 cells retained a normal diploid karyotype, with no detectable chromosome
      abnormalities. Consistent with the bone-forming potential of early passage hMSC
      TERT20 cells, tumors derived from late passage cells expressed early biomarkers
      of osteogenesis. However, hMSC-TERT20 cells were heterogeneous for alpha smooth
      muscle actin (ASMA) expression and one out of six hMSC-TERT20 derived single cell
      clones was strongly ASMA positive. Tumors from this ASMA+ clone had distinctive
      vascular qualities with hot spots of high CD34+ murine endothelial cell density,
      together with CD34- regions with a branching periodic acid Schiff reaction
      pattern. Such clone-specific differences in host vascular response provide novel
      models to explore interactions between mesenchymal stem and endothelial cells.
      Despite the lack of a characteristic chromosomal translocation, the
      histomorphology, biomarkers and oncogenic changes were similar to those prevalent
      for Ewing's sarcomas. The phenotype and ontogenesis of hMSC-TERT20 tumors was
      consistent with the hypothesis that sarcomas may arise from hMSC, providing a
      unique diploid model for exploring human sarcoma biology.

PMID- 18712676
TI  - Allopurinol attenuates L-NAME induced cardiomyopathy comparable to blockade of
      angiotensin receptor.
AB  - It is widely recognized that L-NAME exposed rats develop myocardial fibrosis and
      hypertrophy. The aim of this study was to evaluate the contribution of xanthine
      oxidase (XO) to these phenomena using allopurinol, isolated or associated with
      olmesartan. Thirty adult male Wistar rats were divided into 5 groups (n=6) and
      studied for 5 weeks: L group (L-NAME, 40mg/kg/day); L+A group (L-NAME and
      allopurinol, 40 mg/kg/day); L+O group (L-NAME and olmesartan, 15mg/kg/day); L+A+O
      group (L-NAME, allopurinol, and olmesartan); and control group. L-NAME caused
      arterial hypertension and cardiomyocyte hypertrophy. Hypertension was prevented
      by olmesartan, but not by allopurinol. There was an increase of left ventricular
      mass index in the L-NAME group that was prevented by allopurinol, olmesartan and
      by the combination of both. The increase in mean cardiomyocyte transversal area
      caused by L-NAME was prevented by the allopurinol and olmesartan combination, or
      by olmesartan used as monotherapy, but not by allopurinol alone. There was a
      reduction in the myocardial vascularization index caused by L-NAME which was
      abolished by allopurinol or by olmesartan, but not by the association. L-NAME
      caused a reduction in the total number of cardiomyocyte nuclei. This was
      prevented by olmesartan alone or associated with allopurinol, but not by
      allopurinol alone. We conclude that XO has an important contribution to adverse
      cardiac remodeling in L-NAME exposed animals. Moreover, allopurinol acts without
      interfering with L-NAME induced hypertension. The protective action of this drug
      is comparable to the results obtained with olmesartan. Antioxidative mechanisms
      are proposed to account for the pressure independent effects of allopurinol.

PMID- 18712677
TI  - Substance P and calcitonin gene-related peptide intrinsic choroidal neurons in
      human choroidal whole-mounts.
AB  - To determine the presence in the human choroid of substance P (SP)-and calcitonin
      gene-related peptide (CGRP) positive intrinsic choroidal neurons (ICNs),
      choroidal whole-mounts were processed for indirect immunofluorescence. An
      antibody to a component of the neuronal cytoskeleton, neurofilament 200 kDa (NF
      200), was combined with antibodies to SP and to CGRP (neuropeptides proper to the
      sensory nervous system). The human choroid possesses numerous SP(+) and CGRP(+)
      ICNs. These neurons were observed in the suprachoroid, both in isolation and
      forming microganglia. For both types of ICNs studied, neurons were more numerous
      in the temporal than in the nasal regions. In both locations, SP(+) and CGRP(+)
      ICNs were more abundant in the central choroid (the choroid underneath the
      macular area of the retina), with cell density diminishing outwards to the
      choroidal periphery. There were no appreciable differences between the two
      populations of ICNs studied in terms of size, morphology or immunostaining
      characteristics. In conclusion, given that peripheral sensory innervation could
      be involved in the regulation of both choroidal blood flow and vascular
      architecture, the SP(+) and CGRP(+) ICNs described for the first time in the
      present work may be involved in these mechanisms of vascular regulation.

PMID- 18712678
TI  - Involvement of pro-apoptotic and anti-apoptotic factors in the early development
      of the human pituitary gland.
AB  - The spatial and temporal pattern of appearance of pro-apoptotic caspase-3 and p53
      proteins, and anti-apoptotic bcl-2 protein was investigated in the developing
      pituitary gland of 6 human embryos 5-8-weeks old, using morphological and
      immunohistochemical techniques. Their dynamic appearance was analyzed in the
      Rathke's pouch (future adenohypophysis), mesenchyme, and in the developing
      neurohypophysis. In the 5th and 6th week, caspase-3 positive cells appeared in
      the Rathke's pouch (5%) and stalk (11%), in the mesenchyme, but not in the
      neurohypophysis. In the 6th and 7th week, apoptotic cells were more numerous in
      the caudal part of the Rathke's pouch due to its separation from the oral
      epithelium. Pro-apoptotic p53 protein was detected in all parts of the pituitary
      gland throughout the investigated period. Nuclear condensations characterized
      cells positive to caspase-3 and p53 proteins. Apoptotic cells displayed
      condensations of nuclear chromatin on an ultrastructural level as well. While
      caspase-3 dependent pathway of cell death participated in morphogenesis of the
      adenohypophysis and associated connective tissue, p53-mediated apoptosis most
      likely participates in morphogenesis of all parts of the gland, including
      neurohypophysis. The anti-apoptotic bcl-2 protein was also detected in all parts
      of the developing gland. With advancing development, the positivity to bcl-2
      protein increased in the cells of the adenohypophysis, while it decreased in the
      neurohypophysis. Bcl-2 protein probably prevented cell death in all parts of the
      gland and enhanced cell differentiation. The described pattern of appearance of
      the investigated pro-apoptotic and anti-apoptotic factors might be important for
      normal morphogenesis and function of the pituitary gland.

PMID- 18712679
TI  - Akt pathway as a target for therapeutic intervention in HNSCC.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common form of
      cancer worldwide. One frequent alteration found in this type of cancer is
      overactivation of the PI3K/PTEN/mTOR pathway, of which protein kinase B (PKB)/Akt
      is a central key element, controlling important cellular processes such as
      metabolism, cell size, proliferation and apoptosis, ultimately regulating cell
      growth and survival. Thus, drugs that target Akt directly or elements of the
      pathway are plausible candidates for cancer treatment. Accordingly, numerous
      clinical trials in various phases are being performed for these drugs. In this
      review, we discuss the tumorigenic capacity of Akt and focus on its role in
      HNSCC, paying special attention to the current efforts in treating this cancer in
      a more specific, Akt-targeted way, based on its primordial role in this type of
      cancer.

PMID- 18712680
TI  - TNF-alpha/IL-1/NF-kappaB transduction pathway in human cancer prostate.
AB  - TNFalpha exerts apoptosis throughout an intracellular transduction pathway that
      involves the kinase proteins TRAF-2 (integration point of apoptotic and survival
      signals), ASK1 (pro-apoptotic protein), MEK-4 (p38 activator and metastasis
      suppressor gene), JNK (stress mitogen activated protein kinase) and the
      transcription factor AP-1. TNFalpha also exerts proliferation by p38 activation,
      or when TRAF-2 simultaneously induces the transcription factor NF-kappaB by NIK.
      NIK and p38 may also be activated by IL-1. P38 activated several transcription
      factors such as Elk-1, ATF-2 and NF-kappaB. NIK also may activate NF-kappaB. The
      aim of the present article was to evaluate the different components of this
      TNFalpha/IL-1 transduction pathway in human prostate carcinoma (PC) in comparison
      with normal human prostate. In prostate cancer, pro-apoptotic TNFalpha/AP-1
      pathway is probably inactivated by different factors such as p21 (at ASK-1 level)
      and bcl-2 (at JNK level), or diverted towards p38 or NIK activation. IL-1alpha
      enhances proliferation through IL-1RI that activates either NIK or p38
      transduction pathway. P38 and NIK activate different transcription factors
      related with cell proliferation and survival such as ATF-2, Elk-1 or NF-kappaB.
      In order to search a possible target to cancer prostate treatment we proposed
      that inhibition of several proinflamatory cytokines such as IL-1 and TNFalpha
      might be a possible target for PC treatment, because decrease the activity of all
      transduction pathway members that activate transcription factors as NF-kappaB,
      Elk-1 or ATF-2.

PMID- 18712681
TI  - Nucleolus: the ribosome factory.
AB  - The nucleolus is a nuclear compartment and represents the most obvious and
      clearly differentiated nuclear structure seen in the microscope. Within nucleoli
      most events of ribosome biogenesis, such as ribosomal RNA synthesis, processing,
      and ribosome subunit assembly, take place. Several lines of evidence now show
      that the nucleolus has also numerous non-ribosomal functions. This review is
      focused on the recent progress in our knowledge of how to correlate the known
      biochemical processes taking place in the nucleolus with nucleolar structures
      observed in the microscope. We still lack detailed enough information to
      understand fully the organization and regulation of the processes taking place in
      the nucleolar sub-structures. However, the present power of microscopy techniques
      should allow for an in situ description of the organization of nucleolar
      processes at the molecular level in the years to come.

PMID- 18712682
TI  - A rare cause of dysphonia.
AB  - Although dysphonia is a common complaint among patients seen in an otolaryngology
      clinic, an autoimmune cause of the problem is less common. Autoimmune disease can
      be the source of various laryngologic manifestations, but diagnosis depends on a
      high index of suspicion, careful patient evaluation and testing, and
      videolaryngoscopy (videostroboscopy if available) to uncover specific identifying
      findings. This report describes a patient presenting with upper-range vocal
      difficulties who was found to have early systemic lupus erythematosus.

PMID- 18712683
TI  - In vivo fluorescence of medullary carcinoma of the thyroid: a technology with
      potential to improve visualization of malignant tissue at surgical resection.
AB  - Medullary carcinoma of the thyroid requires aggressive treatment because of its
      potential to metastasize and because of the current limitations of preoperative
      localization and systemic therapy. If these tumors could be made to fluoresce in
      vivo with tagged fluorophore antibodies against tumor antigens, surgeons would be
      able to obtain additional information in the operating room to facilitate a more
      complete resection. Based on the success of our previous work in breast and colon
      cancer models, we conducted an animal study of in vivo tumor fluorescence of a
      human medullary thyroid cell line in which bright tumor fluorescence is visible
      during dissection. To accomplish this, we used an inexpensive and commercially
      available handheld, blue (470 nm), light-emitting diode flashlight and filtered
      goggles (520 nm). This procedure, which we call the fluorescent antibody-assisted
      surgical technique (FAAST), is easy to perform, requires no complex or expensive
      technical equipment, and has the potential to be applied to a wide variety of
      tumors. To the best of our knowledge, this is the first experiment of its kind to
      be reported in the literature.

PMID- 18712684
TI  - Results after intensified therapy for advanced carcinoma of the hypopharynx.
AB  - We conducted a retrospective chart review of 85 patients (95% male) with advanced
      but resectable hypopharyngeal carcinoma to evaluate the effectiveness of an
      intensified multimodal treatment protocol. This protocol involved concomitant
      chemo- and radiotherapy before and after total laryngectomy, partial
      pharyngectomy, and radical neck dissection. Our study population was divided into
      two groups on the basis of extrasurgical therapy. Group A was made up of 19
      patients who had received only postlaryngectomy radiotherapy; 6 of these patients
      had a stage III tumor and 13 had a stage IV tumor. Group B included 66 patients
      who had received the intensified treatment; 1 patient had stage II disease, 12
      had stage III disease, and 53 had stage IV disease. We found no significant
      differences in 5-year survival (p = 0.86) or in disease-free interval (p = 0.57)
      between group A and group B; median survival was 45 and 50 months, respectively.
      Likewise, when we analyzed the patients in both groups according to tumor stage
      (stage III vs. stage IV), we found no significant differences in either 5-year
      survival (group A: p = 0.95; group B: p = 0.18) or disease-free interval (group
      A: p = 0.74; group B: p = 0.17). We conclude that the prognosis of advanced
      hypopharyngeal carcinoma remains poor despite treatment with an intensified
      multimodality protocol. Therefore, the therapeutic strategy should be to
      individualize treatment with the goal of preserving laryngeal function and
      optimizing postoperative quality of life.

PMID- 18712685
TI  - Personality changes and the role of counseling in the rehabilitation of patients
      with laryngeal cancer.
AB  - We conducted a study of 65 adults who had undergone laryngectomy for the
      treatment of laryngeal cancer. Our goal was to identify any abnormal personality
      traits in these patients and to assess the effect that psychological counseling
      might have on correcting these abnormalities and thereby improving postoperative
      voice rehabilitation. A Personality Trait Inventory (PTI) administered to all
      patients preoperatively identified 47 patients who had abnormal scores for at
      least three personality traits. These 47 patients were sent for preoperative
      psychological counseling, and 3 months following surgery, they underwent a follow
      up PTI. At the follow-up assessment, 40 of these patients-32 men and 8 women
      still registered abnormal scores for at least three traits. Half of the men and
      half of the women were randomized to receive 12 sessions of individualized
      psychological counseling over 6 months in addition to standard speech therapy
      (group I); the other patients received speech therapy only (group II). A follow
      up PTI was administered at the completion of psychological counseling and/or
      speech therapy (postoperative month 9). Statistical analysis of the data was
      performed with the paired-samples test. Intragroup analysis of the follow-up PTI
      results revealed that both groups experienced a significant improvement in
      activity scores (p < 0.001) compared with their previous PTI results and that
      group I had significantly better scores for two other PTI traits-cyclothymia
      (mood swings) and depressive tendency (p < 0.05); neither group showed a
      significant improvement in dominance scores. Intergroup comparisons revealed that
      group I's activity and depressive tendency scores were significantly better than
      those of group II; there was no significant difference between the two groups in
      cyclothymia and dominance scores. Finally, comparison of results by sex,
      regardless of group, revealed that men had a significantly higher score for
      dominance and women had significantly higher scores for depressive tendency,
      emotional instability, introversion, and social desirability. We conclude that a
      preoperative personality analysis should be carried out in all patients scheduled
      for laryngectomy to identify those with personality problems that might benefit
      from psychological counseling. Correction of these problems should help in the
      physical, mental, vocational, and social rehabilitation of these patients.

PMID- 18712686
TI  - Drug development research: the process.

PMID- 18712687
TI  - Migration of T-tubes to the middle ear.

PMID- 18712688
TI  - Acute vocal fold hemorrhage after thyroplasty.

PMID- 18712689
TI  - Endoscopic view of a posterior ostium of the ethmoid bulla.

PMID- 18712690
TI  - Focal inflammatory myositis of the paraspinal neck muscles.

PMID- 18712691
TI  - The meatal ganglion in neoplasia and inflammation of the facial nerve.

PMID- 18712692
TI  - Results of exploratory tympanotomy following sudden unilateral deafness and its
      effects on hearing restoration.
AB  - In cases of acute unilateral deafness, no consensus exists as to whether
      tympanotomy and sealing of the round window should be performed routinely. To
      further address this issue, we conducted a retrospective study of pre-, intra-,
      and postoperative findings in 97 patients who had undergone exploratory
      tympanotomy (EXT) after the onset of sudden and severe unilateral deafness. Our
      goal was to ascertain, if we could, whether the benefits of EXT outweigh the
      risks. We also took into account the effects of perilymph fistula (PLF) on the
      etiology of sudden hearing loss and postoperative outcomes. We found that routine
      EXT was indeed beneficial for these patients. It was associated with a very low
      surgical complication rate, and its effects on hearing as assessed by objective
      measures were beneficial. The greatest benefits were seen in patients who
      underwent EXT within 7 days after the onset of their hearing loss. With respect
      to PLF, we found that the presence or absence of the "typical history" of PLF
      (i.e., a sudden unilateral hearing loss within 48 hours after a precipitating
      trauma or physical exertion) had no bearing on whether a PLF was actually present
      in our group; nor was vertigo a reliable predictor of PLF. We recommend that EXT
      be performed on all patients with new-onset acute unilateral deafness, barring
      any contraindications, of course. The absence of a typical history of PLF should
      not dissuade the surgeon from proceeding with EXT.

PMID- 18712693
TI  - Gentamicin injections for Meniere disease: comparison of subjective and objective
      end points.
AB  - This retrospective study reports the overall efficacy and comparative results of
      intratympanic gentamicin injections for disabling vertigo episodes. All patients
      received weekly injections for diagnosed Meniere disease. In Group 1 (81
      patients), treatment end points were determined by subjective complaints of
      imbalance, with resolution of vertigo. In Group 2 (23 patients), treatment end
      points were determined when 2 or more values of nystagmus were demonstrated.
      (Group 2 patients were assessed before initiation of therapy for head-shaking,
      head-thrust, and spontaneous nystagmus using infrared video goggles.) After the
      final injection, all patients had audiograms and balance and oculomotor
      retraining. Gentamicin therapy was determined to be successful based on 3-month
      post-therapy findings of vertigo resolution, stable hearing, normalized
      nystagmus, and functional balance.

PMID- 18712694
TI  - Auditory brainstem response threshold differences in patients with vestibular
      schwannoma: a new diagnostic index.
AB  - Auditory brainstem response (ABR) testing is less sensitive in detecting small
      vestibular schwannomas than medium-size tumors. Magnetic resonance imaging (MRI)
      is more sensitive than ABR alone for small and large tumors, but it carries with
      it increased cost and issues of unavailability and patient discomfort. We
      conducted a prospective pilot study of 7 patients with untreated MRI-proven,
      unilateral vestibular schwannoma to determine if we could increase the
      sensitivity of ABR testing in detecting small tumors. Our method involved the use
      of a new ABR index that is based on threshold differences. All patients underwent
      pure-tone audiometry followed by a determination of behavioral threshold and
      neurodiagnostic threshold ABR in the normal ear, which was used as a control, and
      in the diseased ear. Analysis of results revealed that all 7 patients had an
      abnormal ABR threshold difference, and 5 patients displayed abnormal traditional
      ABR indices. The mean difference between the ABR and behavioral click thresholds
      was 41.4 dB in the diseased ears (with the ABR threshold being higher than the
      click threshold) and 15.8 dB in the normal ears. None of the control ears had a
      threshold difference > 30 dB.

PMID- 18712695
TI  - Epistaxis and its relationship to handedness with use of intranasal steroid
      spray.
AB  - Topical intranasal steroid spray is often used to treat allergic and nonallergic
      rhinitis, and epistaxis is a common side effect. The prospective, observational
      study described was designed to determine the incidence of epistaxis and the
      relationship between the side of bleeding and the hand used to administer the
      spray, as well as the handedness of the patient, in a noninvestigational, real
      world setting. Of 559 consecutive patients using an intranasal steroid for more
      than 3 months, 28 patients (5%) reported epistaxis within the prior 2 months. Of
      the 32 reported sides of bleeding (unilateral and bilateral combined), 25
      episodes (78%) were on the same side as the hand used to apply the spray. A
      strong correlation was found between the side of bleeding and both the hand used
      (p < 0.001) and the handedness of the patient (p < 0.002). Patient instruction on
      technique may reduce the incidence of epistaxis.

PMID- 18712696
TI  - The safety of outpatient UPPP for obstructive sleep apnea: a retrospective review
      of 40 cases.
AB  - We retrospectively reviewed the outcomes of 40 patients who had undergone
      outpatient uvulopalatopharyngoplasty (UPPP) for the treatment of moderate to
      severe obstructive sleep apnea (OSA) in order to determine the safety of the
      procedure in an outpatient setting. Postoperatively, 36 of the 40 patients (90%)
      were discharged home the day of surgery without morbidity; 3 other patients
      stayed overnight for nonmedical reasons, and 1 patient who was already an
      inpatient remained hospitalized for unrelated medical issues. No postoperative
      complications occurred, and all patients reported a resolution of OSA symptoms
      and improvement in sleep. Based on a combination of our data and those of
      previous studies, we conclude that patients with significant OSA can safely
      undergo UPPP as an outpatient procedure. We recommend that guidelines regarding
      the perioperative care of patients with OSA be adjusted to include consideration
      of treatment in an outpatient setting.

PMID- 18712697
TI  - Expression of PCNA and bcl-2 in basaloid squamous cell carcinoma of the larynx: a
      controlled study.
AB  - We investigated the difference in the biologic nature of typical squamous cell
      carcinoma (SCC) and basaloid SCC (BSCC) of the larynx by studying proliferation
      and antiapoptotic markers. We performed an immunohistochemical analysis of the
      expression of proliferating cell nuclear antigen (PCNA) and bcl-2 protein in 15
      patients with laryngeal BSCC and 15 stage- and site-matched controls with typical
      laryngeal SCC. We found no significant difference between the two groups in the
      PCNA index or the frequency of bcl-2 overexpression, nor did we find any
      significant difference in survival. Our findings indicate that the biologic
      nature of typical laryngeal SCC and laryngeal BSCC is similar. In addition, our
      follow-up data suggest that the clinical course of laryngeal BSCC is no worse
      than that of typical laryngeal SCC.

PMID- 18712698
TI  - Tracheal diverticulum: a rare finding in a patient with worsening chronic cough.
AB  - Acquired tracheal diverticulum is a rare clinical entity with only limited
      reports in the literature. We report a case of a tracheal diverticulum that was
      identified as part of a work-up for a worsening cough. In this case the
      diverticulum was observed 2 years after surgical management of a retropharyngeal
      abscess. It was felt that pooling of secretions in the acquired pouch was a
      contributing factor in the exacerbation of the patient's chronic cough. Because
      of the patient's extensive comorbidities, observation and serial computed
      tomography scans were recommended.

PMID- 18712699
TI  - Intratracheal ectopic thyroid tissue presenting with protracted airway
      obstruction: a case report.
AB  - Intratracheal ectopic thyroid tissue is a rare finding, with few cases reported
      in the literature. Ectopic thyroid tissue results when the thyroid gland fails to
      descend to its final position during early development. These lesions present in
      various locations, and the clinician should be aware of their existence and
      presenting signs and symptoms.

PMID- 18712700
TI  - Head and neck manifestations of lymphogranuloma venereum.
AB  - Lymphogranuloma venereum (LGV)--caused by Chlamydia trachomatis serovars L1, L2,
      or L3--rarely occurs in the United States. The disease clinically manifests in
      three stages: primary, secondary, and tertiary. The primary manifestation, a self
      limited genital ulcer at the site of inoculation, often is absent by the time the
      patient seeks medical attention. The most common clinical manifestation of LGV is
      evident in its secondary stage: unilateral tender inguinal and/or femoral
      lymphadenopathy. However, proctocolitis or inflammatory involvement of perirectal
      or perianal lymphatic tissues resulting in fistulas and strictures may also
      occur. The diagnosis of LGV is usually made serologically and by exclusion of
      other causes of inguinal lymphadenopathy or genital ulcers. Doxycycline is the
      preferred treatment; it cures the infection and prevents ongoing tissue damage.
      This case highlights an unusual manifestation of LGV infection--cervical
      lymphadenopathy following suspected oropharyngeal infection with C trachomatis.
      Head and neck manifestations of LGV may become an increasing problem in the
      future if sexual practices such as orogenital contact become more widespread.

PMID- 18712701
TI  - The effects of cigarette smoking and abstinence on auditory verbal learning.
AB  - Smoking has been associated with both enhanced and impaired cognitive
      performance; across a variety of domains, but there is limited evidence
      demonstrating the effects on verbal learning. The current study assessed the
      effect of smoking and abstinence on verbal learning, immediate memory and
      retention using the Auditory Verbal Learning Test (AVLT). Three groups: 20
      smokers, 20 abstaining smokers and 20 non-smoking adults were assessed on the
      AVLT on two occasions. At session one, abstaining smokers refrained from smoking
      for 12 h (pre-cigarette), whilst smokers had continued to smoke to satiety.
      Session two commenced after a 15-min break when both smoking groups were
      instructed to smoke a cigarette, followed by administration of the second version
      of the AVLT (post-cigarette). Abstaining smokers showed significant deficits in
      learning compared to smokers during the pre-cigarette session. Following re
      initiation of smoking in the abstaining smokers, these learning decrements were
      no longer evident. There were trends towards significant group findings in
      immediate memory and retention during the pre-cigarette session, which again were
      no longer evident in the post-cigarette session. These findings provide further
      evidence that smoking abstinence affects verbal learning and furthermore smoking
      simply restores cognitive performance to pre-abstinence levels.

PMID- 18712702
TI  - Identification and characterization of active compounds and their metabolites by
      high-performance liquid chromatography/Fourier transform ion cyclotron resonance
      mass spectrometry after oral administration of a herbal extract of Epimedium
      koreanum Nakai to rats.
AB  - Epimedium is an important traditional Chinese medicine that is widely used
      throughout China as a tonic, aphrodisiac, and antirheumatic medicine. Flavonoids
      are considered to be the active compounds in Epimedium. In the study reported
      here, high-performance liquid chromatography coupled with Fourier transform-ion
      cyclotron resonance mass spectrometry (HPLC/FTICR-MS) was developed to identify
      active compounds and their metabolites after oral administration of a herbal
      extract of Epimedium koreanum Nakai to rats, using parent mass list triggered
      data-dependent multiple-stage accurate mass analysis at a resolving power of 100
      000 in the external calibration mode. Nine flavonoids were identified in rats.
      The chemical formulae with unsaturation numbers calculated from accurate m/z
      values of precursor and product ions were used to assign the structures of
      metabolites and the chemical sites of metabolism. The mass accuracies obtained
      for all full-scan MS and MS(n) spectra were within 3 ppm (<1 ppm in most cases).
      The majority of the metabolites identified have been previously reported, but
      three compounds were noted for the first time in rats. By contrasting the
      analytical results obtained from the herbal extract with those obtained from
      biological specimens, the profile of flavonoid biotransformation in Epimedium was
      obtained and the metabolic pathways of these components, in rats, are described.
      The results should be of use in targeting potential active ingredients in
      Epimedium.

PMID- 18712703
TI  - Fragmentation pathways of heroin-related alkaloids revealed by ion trap and
      quadrupole time-of-flight tandem mass spectrometry.
AB  - The electrospray ionization (ESI) ion trap and quadrupole time-of-flight (QqToF)
      mass spectra of heroin and seven related alkaloids, i.e., morphine, codeine, O-6
      monoacetylmorphine (6-MAM), thebaine, acetylcodeine, papaverine and narcotine,
      have been extensively investigated in this work. The ESI mass spectrometric
      fragmentation pathways of protonated 6-MAM, heroin, acetylcodeine, and thebaine
      were comprehensively elucidated for the first time with the aid of high
      resolution mass spectrometry. It was found that cleavage of the piperidine ring
      was the featured fragmentation route of six of the compounds, although not of
      papaverine and narcotine. In addition, a simple high-performance liquid
      chromatography (HPLC)-based separation method gave baseline resolution of all
      eight components. This study could play an important role in the screening for
      these alkaloids in different matrices by HPLC coupled to tandem mass spectrometry
      (MS/MS).

PMID- 18712704
TI  - Comparison of the oxygen and hydrogen isotopes in the juices of fast-growing
      vegetables and slow-growing fruits.
AB  - We have analyzed the oxygen and hydrogen isotopic composition of juices from
      fruits and vegetables collected from a small orchard in order to investigate the
      differences in isotopic enrichment and evaporation intensity between fast-growing
      vegetables and slow-growing fruits grown under the same climatic conditions. The
      oxygen and hydrogen isotope levels were much higher in the juices of the fruits
      and vegetables than in the source waters in which they grew because of
      evaporation effects. According to our data, fast-growing vegetables are subject
      to greater evaporation than slow-growing fruits. An evaporation experiment using
      the source water showed that the oxygen and hydrogen isotopic composition of the
      60-80% residual fraction was similar to that of the isotopically enriched grape
      juice, whereas those of the plume and tomato juices were very close to that of
      the 80-90% residual fraction, thus proving the effect of evaporation.

PMID- 18712705
TI  - Plasma phospholipids implicated in the matrix effect observed in liquid
      chromatography/tandem mass spectrometry bioanalysis: evaluation of the use of
      colloidal silica in combination with divalent or trivalent cations for the
      selective removal of phospholipids from plasma.
AB  - The feasibility of the use of colloidal silica in combination with a number of
      divalent or trivalent cations for the removal of plasma phospholipids was
      evaluated by sequentially adding the two reagents (i.e., colloidal silica and a
      cation) directly to blank plasma samples or plasma samples spiked with analytes.
      Three representative plasma phospholipids were monitored to determine the
      efficiency of the phospholipids removal under different reagent combinations. The
      recovery of each spiked analyte was also monitored under each condition in order
      to determine if any of the analyte was removed along with the phospholipids. By
      optimizing the amounts of the reagents used and the sequence of the addition of
      the reagents, quantitative and reproducible removal of the phospholipids was
      achieved. Using the finally selected lanthanum cation, the removal of
      phospholipids was achieved with minimal concomitant loss of the ten investigated
      analytes which were carefully selected to incorporate functional groups that
      could potentially interact with the added reagents and hence could be removed
      along with the phospholipids.

PMID- 18712706
TI  - Mangrove trees growing in a very saline condition but not using seawater.
AB  - Mangrove trees, which develop along tropical coasts, are known to use saline
      water uptake. In French Guiana, the high salinity condition is the result of
      seawater evaporation on mud banks formed from the Amazon sediment flumes. In the
      back mangrove a few kilometres inland, groundwater, soil water and the xylem sap
      uptake in the trees remain highly salty, and only very tolerant plants like
      Avicennia germinans can flourish, whereas the less salt-tolerant Rhizophora
      mangle is more difficult to find. Curiously, the same Avicennia trees propagate
      on the seafront. However, stable isotope ratio mass spectrometry (IRMS)
      measurements and ion analysis (high-performance liquid chromatography (HPLC) and
      inductively coupled plasma atomic emission (ICP-AES) spectroscopy reveal that the
      origin of the water in the back mangrove is not seawater. It is freshwater
      percolating into the sand bars from the inland marshes and rainwater during the
      wet season that redissolves a marine evaporite and gives a saline groundwater.
      The absence of barren saltine areas ('tanne') in French Guiana could be explained
      by this freshwater inflow, the aquifer being no longer linked with the ocean.

PMID- 18712707
TI  - Selected ion flow tube mass spectrometry of exhaled breath condensate headspace.
AB  - Collection of exhaled breath condensate (EBC) is a relatively simple noninvasive
      method of breath analysis; however, no data have been reported that would relate
      concentration of volatile compounds in EBC to their gaseous concentrations in
      exhaled air. The aim of the study was to investigate which volatile compounds are
      present in EBC and how their concentrations relate to results of direct breath
      analysis. Thus, samples of EBC were collected in a standard way from several
      subjects and absolute levels of several common volatile breath metabolites
      (ammonia, acetone, ethanol, methanol, propanol, isoprene, hydrogen cyanide,
      formaldehyde and acetaldehyde) were then determined in their headspace using
      selected ion flow tube mass spectrometry (SIFT-MS). Results are compared with
      those from on-line breath analyses carried out immediately before collecting the
      EBC samples. It has been demonstrated that SIFT-MS can be used to quantify the
      concentrations of volatiles in EBC samples and that, for methanol, ammonia,
      ethanol and acetone, the EBC concentrations correlate with the direct breath
      levels. However, the EBC concentrations of isoprene, formaldehyde, acetaldehyde,
      hydrogen cyanide and propanol do not correlate with direct breath measurements.

PMID- 18712708
TI  - Review: Biological relevance of disseminated tumor cells in cancer patients.
AB  - The prognosis of cancer patients is largely determined by the occurrence of
      distant metastases. In patients with primary tumors, this relapse is mainly due
      to clinically occult micrometastasis present in secondary organs at primary
      diagnosis but not detectable even with high resolution imaging procedures.
      Sensitive and specific immunocytochemical and molecular assays enable the
      detection and characterization of disseminated tumor cells (DTC) at the single
      cell level in bone marrow (BM) as the common homing site of DTC and circulating
      tumor cells (CTC) in peripheral blood. Because of the high variability of results
      in DTC and CTC detection, there is an urgent need for standardized methods. In
      this review, we will focus on BM and present currently available methods for the
      detection and characterization of DTC. Furthermore, we will discuss data on the
      biology of DTC and the clinical relevance of DTC detection. While the prognostic
      impact of DTC in BM has clearly been shown for primary breast cancer patients,
      less is known about the clinical relevance of DTC in patients with other
      carcinomas. Current findings suggest that DTC are capable to survive chemotherapy
      and persist in a dormant nonproliferating state over years. To what extent these
      DTC have stem cell properties is subject of ongoing investigations. Further
      characterization is required to understand the biology of DTC and to identify new
      targets for improved risk prevention and tailoring of therapy. Our review will
      focus on breast, colon, lung, and prostate cancer as the main tumor entities in
      Europe and the United States.

PMID- 18712710
TI  - Activating NK cell receptor ligands are differentially expressed during
      progression to cervical cancer.
AB  - Human papillomavirus-induced cervical carcinomas often show impaired expression
      of MHC class I molecules resulting in the inability of tumor cells to directly
      present viral peptides to cytotoxic T lymphocytes. Loss of MHC class I expression
      combined with the expression of activating NK cell receptor ligands renders tumor
      cells potentially susceptible to NK cell attack. Thus, in this study, we analyzed
      the expression of activating NK cell receptor ligands, NK cell accumulation and
      activation status in situ in normal ectocervical tissue (NCT), cervical
      intraepithelial neoplasia (CIN) and squamous cervical carcinoma (CxCa). We
      observed that expression of the DNAM-1 ligand CD155 was frequently upregulated in
      CxCa, but not in CIN. The NKG2D ligand MICA was upregulated in fewer CxCa
      biopsies. In contrast, another NKG2D ligand ULBP2 was preferentially expressed in
      differentiated epithelial cells of NCT. Increased numbers of NK cells were
      detected in CIN as compared to NCT and CxCa. Expression of activating NK cell
      receptor ligands combined with loss of MHC class I was not correlated with
      enhanced NK cell accumulation or activation status. Furthermore, we demonstrate
      that cervical cancer cell lines are killed by the NK cell line, NKL, in a NKG2D-
      and DNAM-1-dependent manner in vitro. Since a significant number of CxCa biopsies
      showed low MHC class I expression combined with high expression of one or more of
      the tested activating NK cell receptor ligands, we conclude that CxCa might be a
      promising target for NK cell-based adoptive immunotherapy.

PMID- 18712711
TI  - Tissue culture-based breast cancer biomarker discovery platform.
AB  - Current cancer biomarkers suffer from low diagnostic sensitivity and specificity
      and have not yet made a major impact on reducing cancer burden. Proteomic methods
      based on mass spectrometry have matured significantly over the past few years and
      hold promise to deliver candidate markers for diagnosis, prognosis or monitoring
      therapeutic response. Because of the complex nature of biological fluids such as
      plasma, biomarker discovery efforts using proteomics have not as yet delivered
      any novel tumor markers. Recently, there has been a rise in the number of
      publications utilizing a cell culture-based model of cancer to identify novel
      candidate tumor markers. The secretome of cancer cell lines constitutes an
      important class of proteins that can act locally and systemically in the body.
      Secreted proteins, in addition to serving as serological markers, play a central
      role in physiology and pathophysiology. In this review, we focus on the
      proteomics of breast cancer and the different strategies to mine for biomarkers,
      with particular emphasis on a cell culture-based model developed in our
      laboratory.

PMID- 18712712
TI  - Rituximab as an adjunct to plasma exchange in TTP: a report of 12 cases and
      review of literature.
AB  - Idiopathic thrombotic thrombocytopenic purpura (TTP) is caused by the production
      of autoantibodies against the Von Willebrand factor cleaving enzyme. This
      provides a rationale for the use of rituximab in this disease. We report a
      retrospective review of 12 patients treated with rituximab for TTP refractory to
      plasma exchange. Eleven patients were treated during initial presentation, and
      one patient was treated for recurrent relapse. Ten patients responded to
      treatment. Median time to response after first dose of rituximab was 10 days (5
      32). Of the 11 patients treated during initial presentation, nine remain free of
      relapse after a median follow-up of 57+ months (1+-79+). Two patients died during
      initial treatment. One patient was lost to follow-up 1 month after achieving
      complete response. The patient treated for recurrent disease during second
      relapse remained disease free for 2years, relapsed and was treated again with
      rituximab, and was in remission for 22 months. She relapsed again, was retreated,
      and has now been in remission for 21+ months. We conclude that rituximab is an
      useful addition to plasma exchange treatment in TTP, but its exact role and
      dosing need to be verified in prospective studies.

PMID- 18712713
TI  - Repeat instability in the 27-39 CAG range of the HD gene in the Venezuelan
      kindreds: Counseling implications.
AB  - The instability of the CAG repeat size of the HD gene when transmitted
      intergenerationally has critical implications for genetic counseling practices.
      In particular, CAG repeats between 27 and 35 have been the subject of debate
      based on small samples. To address this issue, we analyzed allelic instability in
      the Venezuelan HD kindreds, the largest and most informative families ascertained
      for HD. We identified 647 transmissions. Our results indicate that repeats in the
      27-35 CAG range are highly stable. Out of 69 transmitted alleles in this range,
      none expand into any penetrant ranges. Contrastingly, 14% of alleles transmitted
      from the incompletely penetrant range (36-39 CAGs) expand into the completely
      penetrant range, characterized by alleles with 40 or more CAG repeats. At least
      12 of the 534 transmissions from the completely penetrant range contract into the
      incompletely penetrant range of 36-39 CAG repeats. In these kindreds, none of the
      individuals with 27-39 CAGs were symptomatic, even though they ranged in age from
      11 to 82 years. We expect these findings to be helpful in updating genetic
      counseling practices.

PMID- 18712715
TI  - A graphical device to represent the outcomes of a logistic regression analysis.
AB  - BACKGROUND: Ongoing research on the best way to diagnose prostate cancer has
      yielded and will continue to yield vast amounts of information. Based on, for
      example, information from prostate cancer screening trials models have been made
      that enable urologists to predict which man has prostate cancer on the basis of
      pre-biopsy data. In patients with screen detected prostate cancer, the presence
      of indolent disease can now be identified with reasonable certainty by a
      different model. For these men active surveillance may be a better option than
      aggressive treatment with its possible side effects as impotence, incontinence
      and bowel damage. Both models mentioned above are logistic regression models.
      Nomograms enable their use in daily clinical practice. METHODS: Nomograms require
      the memorization and addition of intermediate results. We aimed to design a
      device that has the same function as a nomogram without this draw back. RESULTS:
      A new device that resembles a circular slide rule was developed and is currently
      being tested in prostate cancer diagnosis and in prostate cancer patient
      counseling. CONCLUSIONS: The new device has identical functionality to the
      nomogram without the drawback of the latter. The application of the device is not
      limited to the field of prostate cancer research.

PMID- 18712714
TI  - Genetic variation in the serotonin 2A receptor and suicidal ideation in a sample
      of 270 Irish high-density schizophrenia families.
AB  - Genetic variation in the serotonin 2A receptor (HTR2A) has been associated with
      both schizophrenia and suicidal behavior. Our sample comprised 270 Irish high
      density schizophrenia families (n = 1,408 subjects, including 755 with psychotic
      illness). Diagnoses were generated using a modified SCID. All patients who had at
      least one episode of psychosis were rated on the Operation Criteria Checklist for
      Psychotic Illness (OPCRIT). Lifetime history of suicidal ideation was determined
      from medical records and psychiatric interviews and was scored in the OPCRIT.
      Twelve SNPs were selected for study. Ten of these were tagSNPs derived from
      HapMap data, along with His452Tyr and T102C. We tested for association with
      psychotic illness as a whole, as well as stratified by the presence of suicidal
      ideation, using FBAT and PDTPHASE. Single-marker as well as haplotype-based tests
      using a "sliding window" approach were performed. We observed several 2, 3, and 4
      marker haplotypes near the 3' end of the gene that were over-transmitted to
      psychotic subjects (0.02 </= P </= 0.04). His452Tyr was included in these
      haplotypes but was not itself significant. We also observed modest over
      transmission of a 2-marker haplotype that included T102C (0.04 </= P </= 0.08),
      which was also not itself significant in single-marker analyses. There was no
      significant association in the subgroup of the sample with suicidal ideation.
      Because of multiple testing, these results do not provide support for HTR2A as a
      susceptibility gene for psychotic illness, or for suicidal ideation within
      psychotic illness.

PMID- 18712716
TI  - Unmethylated E-cadherin gene expression is significantly associated with
      metastatic human prostate cancer cells in bone.
AB  - BACKGROUND: The concurrent determination of methylation status of E-cadherin gene
      and E-cadherin protein expression remains scant in metastatic prostate cancer
      cells in bone, the most prevalent site for metastatic growth. Therefore, the
      study was undertaken to ascertain the methylation status of E-cadherin gene, a
      most frequent and known epigenetic mechanism of its regulation, and the protein
      expression in prostate tissue biopsy specimen. METHODS: The methylation of E
      cadherin gene was determined by methylation specific-PCR and the protein
      expression by immunohistochemical method in the consecutive sections of each
      prostate tissue biopsy specimen. RESULTS: The unmethylated E-cadherin gene and
      homogeneous E-cadherin protein expression was significantly associated with BPH
      as compared to the primary prostate carcinoma (Fisher's Exact P < 0.001). A
      significant association was observed between the concurrent methylated gene and
      markedly reduced expression of the protein in the primary prostate cancer cells
      as compared to the BPH cells, suggesting methylation-dependent regulation of the
      gene expression in these cases. In contrast to the primary cancer, a highly
      significant increase in the frequency of metastatic prostate cancer cells in bone
      exhibited the concurrent expression of unmethylated gene and homogeneous protein
      (Fisher's Exact P < 0.001). CONCLUSIONS: The study clearly demonstrated a
      significant association of the concurrent expression of unmethylated E-cadherin
      gene and E-cadherin protein with metastatic prostate cancer cells in bone, and
      that its expression may have a role in the intercellular adhesion in the
      formation of metastatic lesions in bone.

PMID- 18712717
TI  - Cell-specific gene transfection from a gene-functionalized poly(d,l-lactic acid)
      substrate fabricated by the layer-by-layer assembly technique.

PMID- 18712718
TI  - Selenite induces topoisomerase I and II-DNA complexes in K562 leukemia cells.
AB  - The essential trace element selenium is one of the most promising cancer
      chemopreventive agents. Data from preclinical studies have revealed that
      selenite, an inorganic form of selenium, may also be useful in cancer
      chemotherapy. DNA topoisomerases (topos) are the target of several useful
      anticancer drugs. These drugs induce DNA complexes with either topo I or topo II;
      then cellular processing coverts these topo-DNA complexes into permanent DNA
      strand breaks that ultimately lead to cell death. Previous reports have revealed
      that selenite can induce apoptosis in cancer cells selectively and that selenite
      induced apoptosis is preceded by the formation of DNA strand breaks. In vitro
      experiments have shown that selenite induces topo II-DNA complexes, which seem to
      be involved in selenite-induced apoptosis. Using the cell-based assay TARDIS,
      here we show that selenite induces topo II-DNA complexes (topo IIalpha and topo
      IIbeta) in K562 leukemia cells; these complexes appeared in a time-dependent
      manner and correlated with the induction of apoptosis. Cells lacking topo IIbeta
      were resistant to selenite-induced cell growth inhibition, suggesting that this
      isoenzyme is a target for selenite. We report for the first time that selenite
      induces topo I-DNA complexes in K562 cells; the levels of these complexes were
      high at short exposure times and seem to appear before the induction of
      apoptosis. Overall, our results show that selenite induces topo-DNA complexes in
      cells with both topo I and II, and support previous data that suggest that this
      agent has potential for the treatment of cancer.

PMID- 18712719
TI  - Small-molecule inhibitors of microrna miR-21 function.

PMID- 18712720
TI  - Angiostatic activity of obtustatin as alpha1beta1 integrin inhibitor in
      experimental melanoma growth.
AB  - The presented results show the effect of targeting of collagen receptor,
      alpha1beta1 integrin expressed on the endothelial cells on the development of
      experimental melanoma and pathological angiogenesis. Obtustatin, a snake venom
      KTS-disintegrin, was applied as a specific inhibitor of this integrin. This low
      molecular weight peptide revealed a potent therapeutic effect on melanoma
      progression in 2 animal systems, mouse and quail. Its oncostatic effect was
      related to the inhibition of angiogenesis. Obtustatin inhibited the
      neovascularization ratio on the CAM embryo of quail, which was pathologically
      induced by the developing tumor. The i.v. administration of obtustatin completely
      blocked cancer growth of MV3 human melanoma in nude mice. In B16F10 syngeneic
      mouse model treatment with the disintegrin revealed a lower effect, although the
      development of the tumor was significantly reduced for both dosages. The
      mechanism of obtustatin action is related to the blocking of microvascular
      endothelial cell proliferation, which undergoes apoptosis in caspase-dependent
      manner. Summarizing, we present studies of low molecular weight disintegrin,
      obtustatin as a potential therapeutic compound for treatment of melanoma that
      contain a high level of vascularization.

PMID- 18712721
TI  - Formation of alpha-hydroxy-beta-diketones through hydroxylation of isoxazolium
      salts: stereoselective approach to angular cis-diols in polycyclic systems.

PMID- 18712722
TI  - Rosiglitazone, a PPAR gamma agonist: potent promoter of
      hydroxybutyl(butyl)nitrosamine-induced urinary bladder cancers.
AB  - In an initial study to determine if rosiglitazone had chemopreventive activity,
      Fischer-344 female rats were administered twice weekly doses of
      hydroxybutyl(butyl)nitrosamine (OH-BBN), a urinary bladder specific carcinogen,
      for 8 weeks. Two weeks following the last dose of OH-BBN, rats were administered
      rosiglitazone (50 mg/kg BW) daily by gavage for the remainder of the study (7
      months). Only 57% of OH-BBN-treated animals developed palpable urinary bladder
      cancers during the course of the study, while all of the OH-BBN plus
      rosiglitazone treated rats developed large cancers (p < 0.01). Surprisingly,
      examination for PPAR gamma by immunohistochemistry in the urinary bladders of
      rats showed that while untreated bladder urothelium and preneoplastic lesions
      clearly expressed PPAR gamma, frank carcinomas exhibited significantly lower
      levels. This was confirmed by employing microarray studies of the same samples.
      In additional studies, lower doses of rosiglitazone (10, 2 and 0.4 mg/kg BW/day)
      were administered. The 10 mg/kg BW/day dose greatly enhanced bladder cancer
      incidence (p < 0.01). The dose of 2 mg/kg BW/day, which is roughly equivalent to
      a standard human dose, also significantly increased bladder cancer incidence
      (controls, 48%; rosiglitazone-treated, 84%). The lowest dose did not
      significantly increase tumor incidence (rosiglitazone at 0.4 mg/kg BW/day, 64%)
      or tumor weight in the rats, although there was a trend in that direction.
      Rosiglitazone alone (10 mg/kg BW/day) given in the absence of OH-BBN did not
      result in bladder cancer formation when given for 10 months. In summary,
      rosiglitazone over a wide dose range enhanced urinary bladder carcinogenesis in
      the OH-BBN model in rats.

PMID- 18712723
TI  - Enhancing H2 uptake by "close-packing" alignment of open copper sites in metal
      organic frameworks.

PMID- 18712725
TI  - KAI1/CD82 is a novel target of estrogen receptor-mediated gene repression and
      downregulated in primary human breast cancer.
AB  - The cell-surface glycoprotein KAI1 suppresses tumor growth and metastasis in
      various animal models. Downregulation of KAI1 has been implicated in the
      progression of cancer. However, the mechanisms of KAI1 inactivation are poorly
      understood. This is the first study that investigates expression and regulation
      of KAI1 in human breast cancer. KAI1 expression was analyzed on custom-made
      tissue microarrays comprising 209 well-characterized breast cancers and normal
      mammary gland tissue. Strong KAI1 immunoreactivity was observed throughout the
      normal mammary gland epithelium. In breast cancer tissue, KAI1 immunoreactivity
      was lost in 161/209 (77%) cases. Strikingly, KAI1 was preferentially lost in
      estrogen receptor (ER)-positive breast cancers (p < 0.001). This was validated by
      real-time RT-PCR analyses showing a 7.5-fold downregulation of KAI1 mRNA in ER
      positive relative to ER-negative tumors (p = 0.028). Notably, this was also
      corroborated by Affymetrix microarray expression data of an independent cohort of
      49 breast cancers. Class comparison analysis identified KAI1 as downregulated in
      ER-positive tumors. Subsequently, human breast cancer cell lines were employed to
      test a potential role of ER-activity in the downregulation of KAI1, as suggested
      by our expression analyses. Exposure of ER-positive breast cancer cells to
      fulvestrant, a clinically approved ER-antagonist that reverses ER-mediated gene
      repression, induced a significant upregulation of KAI1 and inhibited cell
      proliferation as well as migration. In summary, we demonstrate for the first time
      that KAI1 is a target of ER-mediated gene-repression, and thus, it is
      downregulated in ER-positive breast cancer. Importantly, KAI1 might be
      reinducible by endocrine therapy with ER-antagonists in patients suffering from
      ER-positive breast cancer.

PMID- 18712724
TI  - Variation in lung cancer risk by smoky coal subtype in Xuanwei, China.
AB  - Lung cancer rates in Xuanwei County have been among the highest in China for both
      males and females and have been causally associated with exposure to indoor smoky
      (bituminous) coal emissions that contain very high levels of polycyclic aromatic
      hydrocarbons. There are numerous coal mines across the County. Although lung
      cancer risk is strongly associated with the use of smoky coal as a whole,
      variation in risk by smoky coal subtype has not been characterized as yet. We
      conducted a population-based case-control study of 498 lung cancer cases and 498
      controls, individually matched to case subjects on age (+/-2 years) and sex to
      examine risk by coal subtype. Odds ratios (ORs) and 95% confidence intervals
      (CIs) for coal subtype were calculated by conditional logistic regression,
      adjusting for potential confounders. Overall, smoky coal use was positively and
      statistically significantly associated with lung cancer risk, when compared with
      the use of smokeless coal or wood (OR = 7.7, 95% CI = 4.5-13.3). Furthermore,
      there was a marked heterogeneity in risk estimates for specific subtypes of smoky
      coal (test for heterogeneity: p = 5.17 x 10(-10)). Estimates were highest for
      coal of the Laibin (OR = 24.8, 95% CI = 12.4-49.6) and Longtan (OR = 11.6, 95% CI
      = 5.0-27.2) coal types and lower for coal from other subtypes. These findings
      strongly suggest that in Xuanwei and elsewhere, the carcinogenic potential of
      coal combustion products can exhibit substantial local variation by specific coal
      source.

PMID- 18712726
TI  - Imidazolium-based ionic liquids as efficient shape-regulating solvents for the
      synthesis of gold nanorods.

PMID- 18712727
TI  - Intramolecular Huisgen-type cyclization of platinum-bound pyrylium ions with
      alkenes and subsequent insertion into a benzylic C-H bond.

PMID- 18712730
TI  - Characterisation of nanohybrids of porphyrins with metallic and semiconducting
      carbon nanotubes by EPR and optical spectroscopy.
AB  - Single-walled carbon nanotubes (SWCNTs) are noncovalently functionalised with
      octaethylporphyrins (OEPs) and the resulting nanohybrids are isolated from the
      free OEPs. Electron paramagnetic resonance (EPR) spectroscopy of cobalt(II)OEP,
      adsorbed on the nanotube walls by pi-pi-stacking, demonstrates that the CNTs act
      as electron acceptors. EPR is shown to be very effective in resolving the
      different interactions for metallic and semiconducting tubes. Moreover, molecular
      oxygen is shown to bind selectively to nanohybrids with semiconducting tubes.
      Water solubilisation of the porphyrin/CNT nanohybrids using bile salts, after
      applying a thorough washing procedure, yields solutions in which at least 99% of
      the porphyrins are interacting with the CNTs. Due to this purification, we
      observe, for the first time, the isolated absorption spectrum of the interacting
      porphyrins, which is strongly red-shifted compared to the free porphyrin
      absorption. In addition a quasi-complete quenching of the porphyrin fluorescence
      is also observed.

PMID- 18712728
TI  - ApoG2, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces
      apoptosis and suppresses tumor growth in nasopharyngeal carcinoma xenografts.
AB  - Nasopharyngeal carcinoma (NPC) is a common malignant tumor in South China. It has
      been reported that overexpression of antiapoptotic Bcl-2 family proteins in NPC
      has caused the lack of long-term efficacy of conventional therapies.
      Apogossypolone (ApoG2), a novel small-molecule inhibitor of antiapoptotic Bcl-2
      family proteins, has been discovered as the optimized derivative of gossypol. In
      this study, we found that in NPC cells, ApoG2 totally blocked the antiapoptotic
      function of Bcl-2 family proteins without affecting the expression levels of
      these proteins. ApoG2 selectively inhibited proliferation of 3 NPC cell lines
      (C666-1, CNE-1 and CNE-2) that highly expressed the antiapoptotic Bcl-2 proteins.
      This inhibitory activity was associated with release of cytochrome c, activation
      of caspase-9 and caspase-3 and apoptosis of sensitive NPC cells. However, ApoG2
      had no obvious inhibitory effect on NPC cell line HONE-1, which expressed
      antiapoptotic Bcl-2 and Bcl-xL at a low level. We further found that ApoG2
      effectively suppressed tumor growth of NPC xenografts in nude mice and enhanced
      the antitumor effect of CDDP (cisplatin) on NPC cells in vitro and in vivo.
      Immunohistochemical results showed that the expression of CD31 decreased after
      ApoG2 treatment, which suggested inhibition of angiogenesis in NPC xenografts.
      Our findings strongly suggest that ApoG2 may serve as a novel inhibitor of Bcl-2
      family proteins and, by targeting these proteins, may become a promising drug for
      the treatment of NPC.

PMID- 18712731
TI  - MLH1 -93G>A promoter polymorphism and risk of mismatch repair deficient
      colorectal cancer.
AB  - Rare inherited mutations in the mutL homolog 1 (MLH1) DNA mismatch repair gene
      can confer an increased susceptibility to colorectal cancer (CRC) with high
      penetrance where disease frequently develops in the proximal colon. The core
      promoter of MLH1 contains a common single nucleotide polymorphism (SNP) (-93G>A,
      dbSNP ID:rs1800734) located in a region essential for maximum transcriptional
      activity. We used logistic regression analysis to examine the association between
      this variant and risk of CRC in patients in the United Kingdom. All statistical
      tests were 2 sided. In an analysis of 1,518 patients with CRC, homozygosity for
      the MLH1 -93A variant was associated with a significantly increased 3-fold risk
      of CRC negative for MLH1 protein by immunohistochemistry (odds ratio (OR): AA vs
      GG = 3.30, 95% CI 1.46-7.47, n = 1392, p = 0.004, MLH1 negative vs MLH1 positive
      CRC) and with a 68% excess of proximal CRC (OR: AA vs GG=1.68, 95% confidence
      interval (CI) 1.00-2.83, n = 1,518, p = 0.05, proximal vs distal CRC). These
      findings suggest that the MLH1 -93G>A polymorphism defines a low penetrance risk
      allele for CRC.

PMID- 18712732
TI  - Cooperativity between the dihydrogen bond and the NHC hydrogen bond in LiH-(HCN)n
      Complexes.
AB  - The cooperativity between the dihydrogen bond and the NHC hydrogen bond in LiH
      (HCN)(n) (n=2 and 3) complexes is investigated at the MP2 level of theory. The
      bond lengths, dipole moments, and energies are analyzed. It is demonstrated that
      synergetic effects are present in the complexes. The cooperativity contribution
      of the dihydrogen bond is smaller than that of the NHC hydrogen bond. The three
      body energy in systems involving different types of hydrogen bonds is larger than
      that in the same hydrogen-bonded systems. NBO analyses indicate that orbital
      interaction, charge transfer, and bond polarization are mainly responsible for
      the cooperativity between the two types of hydrogen bonds.

PMID- 18712733
TI  - Optical contrast agents and imaging systems for detection and diagnosis of
      cancer.
AB  - Molecular imaging has rapidly emerged as a discipline with the potential to
      impact fundamental biomedical research and clinical practice. Within this field,
      optical imaging offers several unique capabilities, based on the ability of cells
      and tissues to effect quantifiable changes in the properties of visible and near
      infrared light. Beyond endogenous optical properties, the development of
      molecularly targeted contrast agents enables disease-specific morphologic and
      biochemical processes to be labeled with unique optical signatures. Optical
      imaging systems can then provide real-time visualization of pathophysiology at
      spatial scales from the subcellular to whole organ levels. In this article, we
      review fundamental techniques and recent developments in optical molecular
      imaging, emphasizing laboratory and clinical systems that aim to visualize the
      microscopic and macroscopic hallmarks of cancer.

PMID- 18712734
TI  - Long-term population-based risks of breast cancer after childhood cancer.
AB  - Previous studies have reported substantially increased risks of breast cancer
      among survivors of childhood cancer at 10-20 years posttreatment. Whether these
      excess risks are sustained beyond 40 years of age when general population
      incidence of breast cancer begins its steep increase is largely unknown. We
      quantified the risk of breast cancer in adult female survivors with considerably
      more survivors followed-up beyond 40 years of age than previously available.
      Standardized Incidence Ratios (SIR), Excess Absolute Risks (EAR), and cumulative
      incidence were calculated within a population-based cohort of 8,093 female
      survivors of childhood cancer. Poisson regression models were used to model SIRs
      and EARs in a multivariable setting. Eighty-one survivors developed a primary
      breast cancer, where 37.5 were expected (SIR= 2.2, 95% CI: 1.7-2.7). SIRs
      decreased significantly with increasing attained age (p(trend) < 0.001) to an SIR
      of 0.9 (95% CI: 0.5-1.8) at ages beyond 50 years; EARs increased significantly to
      about 40 years of age (p(trend) < 0.001) but then plateau. Between 30 and 49
      years of age survivors experienced approximately 1 extra breast cancer per 1,000
      survivors per year. Overall, 3% developed breast cancer by the age of 50. The
      substantially increased relative risks of breast cancer observed at 10-20 years
      postdiagnosis are not sustained into ages at which the risk of breast cancer in
      the general population becomes substantial. Among women who survived to an age of
      at least 50 years there is currently no evidence of an increased risk of breast
      cancer.

PMID- 18712735
TI  - Synthesis, antiproliferative evaluation, and structure-activity relationships of
      3-arylquinolines.

PMID- 18712737
TI  - Stereoretentive halogenations and azidations with titanium(IV) enabled by
      chelating leaving groups.

PMID- 18712736
TI  - Antiproliferative effects of AVN944, a novel inosine 5-monophosphate
      dehydrogenase inhibitor, in prostate cancer cells.
AB  - Inosine 5-monophosphate dehydrogenase II, a key enzyme in the de novo synthesis
      of purine nucleotides, is expressed in prostate tumors and prostate cancer cells.
      AVN944 is a new, specific, noncompetitive IMPDH inhibitor. In this study, we
      investigated the effects of IMPDH inhibitor AVN944 on LNCaP, CWR22Rv1, DU145 and
      PC-3 human prostate cancer cells. AVN944 inhibited proliferation of these 4
      prostate cancer cell lines and was associated with cell cycle G1 arrest of LNCaP
      cells and S-phase block of androgen-independent CWR22Rv1, DU145 and PC-3 cells.
      AVN944 induced caspase-dependentand caspase-independent cell death in LNCaP,
      CWR22Rv1, and DU145 cells. AVN944 induced expression of p53-target proteins Bok,
      Bax and Noxa in androgen-responsive cell lines and suppressed expression of
      survivin in prostate cancer cells regardless of their androgen sensitivity.
      AVN944 also induced differentiation of androgen-independent prostate cancer cells
      as indicated by morphological changes and increased expression of genes coding
      for prostasomal proteins, keratins and other proteins, including tumor suppressor
      genes MIG-6 and NDRG1. AVN944-differentiated androgen-independent DU145 and PC-3
      cells are sensitized to TRAIL-induced apoptosis as demonstrated by induction of
      caspases and PARP cleavage. In summary, AVN944 inhibited the growth of human
      prostate cancer cells by inducing cell cycle arrest, cell death as well as
      differentiation. AVN944 is a novel, promising therapeutic agent that might be
      combined with other agents for treatment of human prostate cancer.

PMID- 18712738
TI  - Differential subcellular localisation of the tumour suppressor protein LIMD1 in
      breast cancer correlates with patient survival.
AB  - The tumour suppressor gene (TSG) LIM domain containing protein 1 (LIMD1) has been
      associated with transformation of epithelial cells of the lung and its expression
      is downregulated in all lung tumour samples tested compared to normal lung
      matched controls. In the first study of its kind we used an anti-LIMD1 specific
      monoclonal antibody to investigate expression/localisation of the LIMD1 protein
      in a well-characterised tissue microarray of breast cancers and normal adjacent
      epithelia. Comparison of tumour with adjacent normal and distant normal tissue
      demonstrated that LIMD1 expression is moderate to high compared to tumour. There
      was also a significant correlation with histological grade (p = 0.0001), tumour
      size (p = 0.013) and tumour type (p = 0.004) indicating an association with
      aggressive disease. Cytoplasmic LIMD1 expression was seen in 99.3% of cases, with
      43.1% showing both nuclear and cytoplasmic localisation. Absence/loss of nuclear
      staining showed a strong correlation with patient survival and was indicative of
      poor prognosis (p = 0.033). There was no association with lymph node status and
      other clinicopathological parameters. Nuclear staining was more pronounced in
      better prognosis tumours and normal tissue. This study demonstrates that LIMD1
      represents a novel prognostic marker for breast cancer. Combined with the fact
      that LIMD1 expression is downregulated in lung cancers this clearly indicates
      that LIMD1 may represent a critical TSG, the function of which is deregulated via
      overall loss of expression and/or relocalisation within the cell during tumour
      development. The possible functions of LIMD1 localisation within the nucleus and
      cytoplasm and its relationship to tumour prognosis are discussed.

PMID- 18712739
TI  - Hydrolytic stability of hydrazones and oximes.

PMID- 18712740
TI  - Ruthenium(II) pyridylamine complexes with diimine ligands showing reversible
      photochemical and thermal structural change.
AB  - Ruthenium(II)-TPA-diimine complexes, [Ru(TPA)(diimine)]2+ (TPA=tris(2
      pyridylmethyl)amine; diimine=2,2'-bipyridine (bpy), 2,2'-bipyrimidine (bpm), 1,10
      phenanthroline (phen)) were synthesized and characterized by spectroscopic and
      crystallographic methods. Their crystal structures demonstrate severe steric
      hindrance between the TPA and diimine ligands. They exhibit drastic structural
      changes on heating and photoirradiation at their MLCT bands, which involve
      partial dissociation of the tetradentate TPA ligand to exhibit a facially
      tridentate mode accompanied by structural change and solvent coordination to give
      [Ru(TPA)(diimine)(solvent)]2+ (solvent=acetonitrile, pyridine). The incoming
      solvent molecules are required to have pi-acceptor character, since sigma
      donating solvent molecules do not coordinate. The thermal process is irreversible
      dissociation to give the solvent-bound complexes, which takes place by an
      interchange associative mechanism with large negative activation entropies. The
      photochemical process is a reversible reaction reaching a photostationary state,
      probably by a dissociative mechanism involving a five-coordinate intermediate to
      afford the same product as obtained in the thermal reaction. Quantum yields of
      the forward reactions to give dissociated products were lower than those of the
      backward reactions to recover the starting complexes. In the photochemical
      process, the conversions of the forward and backward reactions depend on the
      absorption coefficients of the starting materials and those of the products at
      certain wavelength, as well as the quantum yields of those reactions. The
      reversibility of the motions can be regulated by heating and by photoirradiation
      at certain wavelength for the recovery process. In the bpm system, we could
      achieve about 90 % recovery in thermal/photochemical structural interconversion.

PMID- 18712741
TI  - Comparative study on the structural, optical, and electrochemical properties of
      bithiophene-fused benzo[c]phospholes.
AB  - Three types of bithiophene-fused benzo[c]phospholes were successfully prepared by
      Ti(II)-mediated cyclization of the corresponding dialkynylated bithiophene
      derivatives as a key step. Each sigma(3)-phosphorus center of the
      benzo[c]phosphole subunits was readily transformed into sigma(4)-phosphorus
      center by Au coordination or oxygenation. In addition, the bithiophene subunit
      was functionalized at the alpha,alpha'-carbon atoms by Pd-catalyzed cross
      coupling reactions with heteroarylmetals and by an S(N)Ar reaction with
      hexafluorobenzene. The experimentally observed results (NMR spectroscopy, X-ray
      analysis, UV/Vis absorption/fluorescence spectroscopy, and cyclic/differential
      pulse voltammetry) have revealed that the structural, optical, and
      electrochemical properties of the bithiophene-fused benzo[c]phospholes vary
      considerably depending on the pi-conjugation modes at the bithiophene subunits
      and the substituents of the heterocyclopentadiene components. The appropriately
      ring-annulated sigma(3)-P derivatives and sigma(4)-P-AuCl complexes were found to
      emit fluorescence in the orange-red region, and the sigma(4)-P-oxo derivatives
      proved to undergo reversible one-electron reduction at -1.4 to -1.8 V (vs
      ferrocene/ferrocenium). These results indicate that the bithiophene-fused
      benzo[c]phospholes possess narrow HOMO-LUMO gaps and low-lying LUMOs, which was
      confirmed by density functional theory calculations of their model compounds. The
      time-of-flight measurement of an ITO/benzo[c]phosphole/Al device showed that the
      electron mobility in the P-oxo derivative is one-order higher than that in Alq(3)
      at low electric fields. The present study demonstrates that the arene-fused
      benzo[c]phosphole skeleton could be a highly promising platform for the
      construction of a new class of phosphole-based optoelectrochemical materials.

PMID- 18712743
TI  - An easy single-step synthesis of platinum nanoparticles embedded in carbon.

PMID- 18712742
TI  - P--P bond cleavage of tetraphenyltetraphosphane-1,4-diide facilitated by
      nickel(0).
AB  - One equivalent of [Na2(thf)5-(P4Ph4)] (1) reacts with one equivalent of
      [Ni(cod)2] (cod=1,5-cyclooctadiene) to give the unexpected ionic compound
      [Na(Et2O)3][Na3(Et2O)2Ni3(micro-P2Ph2)2-(P2Ph2)3] (2), whereas the reaction of
      [Ni(cod)2] with the less reactive [K2(pmdeta)2(P4Ph4)] (3) leads to the formation
      of [K(pmdeta)]2[Ni(P4Ph4)-(P2Ph2)] (4) (PMDETA=NMe(CH2CH2NMe2)2), in which K--Ni
      interactions are observed. The calculations for 4 confirm the structural
      parameters obtained by X-ray diffraction studies. A shared electron number (SEN)
      analysis was applied to investigate the K...Ni interactions. These studies
      indicate a SEN value of a typical three-center, two-electron bond for K1-Ni-K2
      indicating a covalent contribution in the interaction between nickel and
      potassium.

PMID- 18712744
TI  - Frontside versus Backside S(N)2 substitution at group 14 atoms: origin of
      reaction barriers and reasons for their absence.
AB  - We have theoretically studied the gas-phase nucleophilic substitution at group-14
      atoms (S(N)2@A) in the model reactions of Cl(-)+AH(3)Cl (A=C, Si, Ge, Sn, and Pb)
      using relativistic density functional theory (DFT) at ZORA-OLYP/TZ2P. Firstly, we
      wish to explore and understand how the reaction coordinate zeta, and potential
      energy surfaces (PES) along zeta, vary as the center of nucleophilic attack
      changes from carbon to the heavier group-14 atoms. Secondly, a comparison between
      the more common backside reaction (S(N)2-b) and the frontside pathway (S(N)2-f)
      is performed. The S(N)2-b reaction is found to have a central barrier for A=C,
      but none for the other group-14 atoms, A=Si-Pb. Relativistic effects destabilize
      reactant complexes and transition species by up to 10 kcal mol(-1) (for S(N)2
      f@Pb), but they do not change relative heights of barriers. We also address the
      nature of the transformation in the frontside S(N)2-f reactions in terms of
      turnstile rotation versus Berry-pseudorotation mechanism.

PMID- 18712745
TI  - Medicinal organometallic chemistry: designing metal arene complexes as anticancer
      agents.
AB  - The field of medicinal inorganic chemistry is rapidly advancing. In particular
      organometallic complexes have much potential as therapeutic and diagnostic
      agents. The carbon-bound and other ligands allow the thermodynamic and kinetic
      reactivity of the metal ion to be controlled and also provide a scaffold for
      functionalization. The establishment of structure-activity relationships and
      elucidation of the speciation of complexes under conditions relevant to drug
      testing and formulation are crucial for the further development of promising
      medicinal applications of organometallic complexes. Specific examples involving
      the design of ruthenium and osmium arene complexes as anticancer agents are
      discussed.

PMID- 18712746
TI  - Total synthesis of potent antitumor agent (-)-lasonolide A: a cycloaddition-based
      strategy.
AB  - A detailed account of the enantioselective total synthesis of (-)-lasonolide A is
      described. Our initial synthetic route to the top tetrahydropyran ring involved
      Evans asymmetric alkylation as the key step. Initially, we relied on the
      diastereoselective alkylation of an alpha-alkoxyacetimide derivative containing
      an alpha' stereogenic center and investigated such an asymmetric alkylation
      reaction. Although alkylation proceeded in good yield, the lack of
      diastereoselectivity prompted us to explore alternative routes. Our subsequent
      successful synthetic strategies involved highly diastereoselective cycloaddition
      routes to both tetrahydropyran rings of lasonolide A. The top tetrahydropyran
      ring was constructed stereoselectively by an intramolecular 1,3-dipolar
      cycloaddition reaction. The overall process constructed a bicyclic isoxazoline,
      which was later unravelled to a functionalized tetrahydropyran ring as well as a
      quaternary stereocenter present in the molecule. The lower tetrahydropyran ring
      was assembled by a Jacobsen catalytic asymmetric hetero-Diels-Alder reaction as
      the key step. The synthesis also features a Lewis acid catalyzed epoxide opening
      to form a substituted ether stereoselectively.

PMID- 18712747
TI  - Synthesis of recyclable fluorous chiral ligands and evaluation of their catalytic
      activity toward asymmetric addition of dimethylzinc to aldehydes.
AB  - The asymmetric addition of Me(2)Zn to aldehydes is very slow and mostly gives low
      ee values. Previously, we reported the synthesis of a fluorous chiral ligand,
      (4R,5S,alpha'R)-2,2-dimethyl-alpha,alpha,alpha'-tris(perfluorooctyl)-2,3
      dioxolane-4,5-dimethanol (1 a), derived from tartarate as a chiral pool. Ligand 1
      a showed high activity toward the addition of Me(2)Zn to aldehydes with high
      enantiomeric excess. However, the very high content of fluorine makes 1 a
      difficult to dissolve in common solvents; hence, much solvent is required, which
      limits its use. This report describes the modification of 1 a by replacing either
      the perfluorooctyl groups with shorter perfluoroalkyl ones or the acetone ketal
      part with cyclohexanone ketal. The perfluorobutyl analogue 1 c is much more
      soluble than 1 a and shows comparable asymmetric induction toward the addition of
      Me(2)Zn to aldehydes. Furthermore, 1 c has a much lower molecular weight than 1
      a. This means that 1 c is used in smaller amounts (weight) than 1 a. The
      cyclohexanone ketal analogue 1 d is more soluble than 1 a and more easily
      synthesized owing to its high solubility and ease of crystallization. Ligand 1 d
      showed much higher asymmetric induction toward cyclohexanecarbaldehyde, a
      branched aldehyde, than 1 a. Thus, 1 a was modified into ligands with higher
      performance.

PMID- 18712748
TI  - Synthesis and biological characterisation of targeted pro-apoptotic peptide.
AB  - We report herein the synthesis and in vitro assay of new, multimeric RGD-peptide
      conjugates for cell-targeted drug delivery. We generated a peptide scaffold
      comprising two functional domains, one a tumour blood vessel "homing" motif and
      the other a programmed cell-death-inducing peptide sequence. RGD peptides were
      selected to direct the molecular conjugate to alpha(V)beta(3) integrin-containing
      tumour cells. The pro-apoptotic (Lys-Leu-Ala-Lys-Leu-Ala-Lys)(2) peptide was
      found to be nontoxic outside cells, but toxic when internalized into targeted
      cells as it disrupted the mitochondrial membrane. The synthesis of these targeted
      pro-apoptotic conjugates was carried out by assembling three different units
      (that is, scaffold, RGD units and pro-apoptotic peptide) through chemoselective
      ligations. We show that one compound displays significant biological effect in
      alpha(V)beta(3) integrin-containing tumour cells.

PMID- 18712749
TI  - Constructing and analyzing the fitness landscape of an experimental evolutionary
      process.
AB  - Iterative saturation mutagenesis (ISM) is a promising approach to more efficient
      directed evolution, especially for enhancing the enantioselectivity and/or
      thermostability of enzymes. This was demonstrated previously for an epoxide
      hydrolase (EH), after five sets of mutations led to a stepwise increase in
      enantioselectivity. This study utilizes these results to illuminate the nature of
      ISM, and identify the reasons for its operational efficacy. By applying a
      deconvolution strategy to the five sets of mutations and measuring the
      enantioselectivity factors (E) of the EH variants, DeltaDeltaG( not equal) values
      become accessible. With these values, the construction of the complete fitness
      pathway landscape is possible. The free energy profiles of the 5!=120
      evolutionary pathways leading from the wild-type to the best mutant show that 55
      trajectories are energetically favored, one of which is the originally observed
      route. This particular pathway was analyzed in terms of epistatic effects
      operating between the sets of mutations at all evolutionary stages. The degree of
      synergism increases as the stepwise evolutionary process proceeds. When
      encountering a local minimum in a disfavored pathway, that is, in the case of a
      dead end, choosing another set of mutations at a previous stage puts the
      evolutionary process back on an energetically favored trajectory. The type of
      analysis presented here might be useful when evaluating other mutagenesis methods
      and strategies in directed evolution.

PMID- 18712750
TI  - Putting the pieces together: histone H2B ubiquitylation directly stimulates
      histone H3K79 methylation.
AB  - Employing an in vitro reconstitution approach, McGinty et al. studied the
      mechanism of stimulation of the Dot1-catalysed histone H3 methylation at Lys79 by
      histone H2B ubiquitylation at Lys120. To generate nucleosome particles that carry
      the ubiquitylation at Lys120, they chemically connected three polypeptides-the
      main parts of histone H3 and ubiquitin expressed in bacteria and a branched
      synthetic peptide. Using the semisynthetically produced nucleosome substrates and
      purified Dot1 enzyme, they showed that Dot1 is directly stimulated by the
      ubiquitylation, thus ruling out the need for further protein factors to mediate
      the effect.

PMID- 18712751
TI  - Controlled growth of peptide nanoarrays on Si/SiOx substrates.

PMID- 18712752
TI  - An ApoA-I mimetic peptide high-density-lipoprotein-based MRI contrast agent for
      atherosclerotic plaque composition detection.
AB  - Cardiovascular disease is one of the prime causes of mortality throughout the
      world and there is a need for targeted and effective contrast agents to allow
      noninvasive imaging of the cholesterol-rich atherosclerotic plaques in arteries.
      A new, fully synthetic, high-density lipoprotein (HDL)-mimicking MRI contrast
      agent is developed, which enhances macrophage-rich areas of plaque in a mouse
      model of atherosclerosis by 94%. Confirmation of the targeting of this
      nanoparticulate agent is achieved using confocal microscopy by tracking a
      fluorescent lipid incorporated into the nanoparticle.

PMID- 18712753
TI  - Enhancement of radiation cytotoxicity in breast-cancer cells by localized
      attachment of gold nanoparticles.
AB  - Gold nanoparticles (GNPs) and modified GNPs having two kinds of functional
      molecules, cysteamine (AET) and thioglucose (Glu), are synthesized. Cell uptake
      and radiation cytotoxicity enhancement in a breast-cancer cell line (MCF-7)
      versus a nonmalignant breast-cell line (MCF-10A) are studied. Transmission
      electron microscopy (TEM) results show that cancer cells take up functional Glu
      GNPs significantly more than naked GNPs. The TEM results also indicate that AET
      capped GNPs are mostly bound to the MCF-7 cell membrane, while Glu-GNPs enter the
      cells and are distributed in the cytoplasm. After MCF-7 cell uptake of Glu-GNPs,
      or binding of AET-GNPs, the in vitro cytotoxicity effects are observed at 24, 48,
      and 72 hours. The results show that these functional GNPs have little or no
      toxicity to these cells. To validate the enhanced killing effect on cancer cells,
      various forms of radiation are applied such as 200 kVp X-rays and gamma-rays, to
      the cells, both with and without functional GNPs. By comparison with irradiation
      alone, the results show that GNPs significantly enhance cancer killing.

PMID- 18712754
TI  - Photoactivation of CdSe/ZnS quantum dots embedded in silica colloids.
AB  - A study of the influence of the local environment on the light-induced
      luminescence enhancement of CdSe/ZnS quantum dots (QD) embedded in silica
      colloids that are dispersed in various solvents is presented. The
      photoluminescence of the embedded QD is enhanced up to a factor of ten upon
      photoactivation by ultraviolet or visible light. This enhancement is strongly
      dependent on the local environment. The thickness-dependent permeability of the
      silica shell covering the QD controls the influence of the solvent on the QD. If
      foreign ions are present the activation state is stabilized after termination of
      the activation, whereas in their absence the process is partially reversible. A
      new qualitative model for the photoactivation of QD in various environments is
      developed. It comprises light-induced passivation and subsequent oxidation
      processes. The embedded QD also retain their fluorescence quantum yield inside
      living cells. Moreover, they can be activated for many hours in living cells by
      laser radiation in the visible regime.

PMID- 18712755
TI  - Response of HEK293 and CHO cells overexpressing fusiogenic syncytin-1 to
      mitochondrion-mediated apoptosis induced by antimycin A.
AB  - Apoptosis is essential for the regulation of cellular homeostasis in the placenta
      and is also involved in the pathophysiology of pregnancy-related diseases such as
      pre-eclampsia and intrauterine growth restriction (IUGR). Syncytin-1, a
      fusiogenic glycoprotein of endogenous-retroviral origin expressed in human
      trophoblasts, facilitates placental syncytium formation and is found reduced in
      pre-eclamptic placentas. We focus here on the mitochondrial apoptotic pathway and
      investigate whether the overexpression of syncytin-1 in HEK293-52 (human
      embryonic kidney cells) and CHO-52 cells influences the apoptotic response to the
      mitochondrial inhibitor antimycin A (AA). After the induction of apoptosis by 5
      microM AA and incubation for up to 36 h in the absence of serum, the mean
      apoptotic rate was reduced by 15-30% in syncytin-1 transfected cells compared
      with mock-transfectants. After 12 h of challenge with AA we found lower
      cytochrome c levels in the cytoplasmic protein fraction and higher amounts in the
      mitochondrial fraction in syncytin-1 transfectants compared with mock
      transfectants. We observed a decreased Mitotracker Red staining of mitochondria
      following AA challenge for 24 h in mock-treated CHO cells, in particular,
      compared with syncytin-1 transfectants. Moreover, we found a reduced activation
      of caspase 9 in syncytin-1 transfected HEK293-52 cells after 48 h of apoptotic
      challenge compared to mock-transfectants. However, a high expression of anti
      apoptotic Bcl-x(L) was found in both cell types. Using syncytin-1 transfected
      HEK293-52 cells and CHO-52 cells, we provide initial evidence that syncytin-1 may
      exert its anti-apoptotic function at the mitochondrial level. A reduced release
      of cytochrome c followed by a diminished activation of caspase 9 is a possible
      mechanism.

PMID- 18712760
TI  - The Journal of Gene Medicine. In this issue.

PMID- 18712761
TI  - Long-term survivor model with bivariate random effects: applications to bone
      marrow transplant and carcinoma study data.
AB  - Cured patients (or the so-called long-term survivors) are increasingly being
      observed in clinical trial studies. As exemplified in two data sets, the bone
      marrow transplantation study for leukaemia patients and the multi-centre study
      for patients with carcinoma in the oropharynx, a considerable portion of the
      patients in these studies are deemed to be cured. With the presence of random
      hospital/centre effects, a long-term survivor model with bivariate random effects
      is proposed to analyse clustered survival data with a possible portion of cured
      patients. This model extends earlier work by allowing random effects in both the
      cured fraction and the hazard function parts to follow a bivariate normal
      distribution, which gives a generalized model with an additional correlation
      parameter governing the relationship between the recovery probability and the
      instantaneous failure rate due to the hospital/centre effects. By adopting the
      GLMM formulation, random effects are incorporated in the model via the linear
      predictor terms. REML estimation of parameters is achieved via the EM algorithm.
      Application to the two sets of data illustrates the usefulness of the proposed
      model. A simulation study is conducted to assess the performance of the
      estimators, under the proposed numerical estimation scheme.

PMID- 18712762
TI  - Adapting the stretched sample method from tissue profiling to imaging.
AB  - The characterization and localization of peptides and proteins in tissues
      provides information that aids in understanding their function and in
      characterizing disease states. Over the past decades, the use of MS for the
      profiling and imaging of biological compounds from tissues has evolved into a
      powerful modality to accomplish these studies. One recently described sampling
      approach, the stretched sample method (Monroe, E. B. et al.., Anal. Chem. 2006,
      78, 6826-6832), places a tissue section onto an array of glass beads embedded on
      a Parafilm M membrane. When the membrane is stretched, it separates the tissue
      section into thousands of cell-sized pieces for tissue profiling by MALDI-MS. The
      physical separation between beads eliminates analyte redistribution during matrix
      application and allows long analyte extraction periods without loss of spatial
      resolution. Here, we enhance this sampling approach by introducing algorithms
      that enable the reconstruction of ion images from these stretched samples. As the
      first step, a sample-tailored data acquisition method is devised to obtain mass
      spectra exclusively from the beads, thereby reducing the time, instrument
      resources, and data handling required for such MS imaging (MSI) experiments.
      Next, an image reconstruction algorithm matches data acquired from the stretched
      sample to the initial bead locations. The efficacy of this method is demonstrated
      using peptide-coated beads with known peptide distributions and appears well
      suited to the MSI of heterogeneous tissue samples.

PMID- 18712763
TI  - High-throughput proteomic analysis of formalin-fixed paraffin-embedded tissue
      microarrays using MALDI imaging mass spectrometry.
AB  - A novel method for high-throughput proteomic analysis of formalin-fixed paraffin
      embedded (FFPE) tissue microarrays (TMA) is described using on-tissue tryptic
      digestion followed by MALDI imaging MS. A TMA section containing 112 needle core
      biopsies from lung-tumor patients was analyzed using MS and the data were
      correlated to a serial hematoxylin and eosin (H&E)-stained section having various
      histological regions marked, including cancer, non-cancer, and normal ones. By
      correlating each mass spectrum to a defined histological region, statistical
      classification models were generated that can sufficiently distinguish biopsies
      from adenocarcinoma from squamous cell carcinoma biopsies. These classification
      models were built using a training set of biopsies in the TMA and were then
      validated on the remaining biopsies. Peptide markers of interest were identified
      directly from the TMA section using MALDI MS/MS sequence analysis. The ability to
      detect and characterize tumor marker proteins for a large cohort of FFPE samples
      in a high-throughput approach will be of significant benefit not only to
      investigators studying tumor biology, but also to clinicians for diagnostic and
      prognostic purposes.

PMID- 18712764
TI  - Multiplexed glycoproteomic analysis of glycosylation disorders by sequential yolk
      immunoglobulins immunoseparation and MALDI-TOF MS.
AB  - This study applied yolk immunoglobulins immunoaffinity separation and MALDI-TOF
      MS for clinical proteomics of congenital disorders of glycosylation (CDG) and
      secondary glycosylation disorders [galactosemia and hereditary fructose
      intolerance (HFI)]. Serum transferrin (Tf) and alpha1-antitrypsin (AAT) that are
      markers for CDG, were purified sequentially to obtain high-quality MALDI mass
      spectra to differentiate single glycoforms of the native intact glycoproteins.
      The procedure was found feasible for the investigation of protein
      macroheterogeneity due to glycosylation site underoccupancy then ensuing the
      characterization of patients with CDG group I (N-glycan assembly disorders).
      Following PNGase F digestion of the purified glycoprotein, the characterization
      of protein microheterogeneity by N-glycan MS analysis was performed in a patient
      with CDG group II (processing disorders). CDG-Ia patients showed a typical
      profile of underglycosylation where the fully glycosylated glycoforms are always
      the most abundant present in plasma with lesser amounts of partially and
      unglycosylated glycoforms in this order. Galactosemia and HFI are potentially
      fatal diseases, which benefit from early diagnosis and prompt therapeutic
      intervention. In symptomatic patients with galactosemia and in those with HFI,
      MALDI MS of Tf and AAT depicts a hypoglycosylation profile with a significant
      increase of underglycosylated glycoforms that reverses by dietary treatment,
      representing a clue for diagnosis and treatment monitoring.

PMID- 18712765
TI  - A study of the Candida albicans cell wall proteome.
AB  - Considering the importance of proteins in the structure and function of the cell
      wall of Candida albicans, we analyzed the cell wall subproteome of this important
      human pathogen by LC coupled to MS (LC-MS) using different protein extraction
      procedures. The analyzed samples included material extracted by hydrogen fluoride
      pyridine (HF-pyridine), and whole SDS-extracted cell walls. The use of this
      latter innovative procedure gave similar data as compared to the analysis of HF
      pyridine extracted proteins. A total of 21 cell wall proteins predicted to
      contain a signal peptide were identified, together with a high content of
      potentially glycosylated Ser/Thr residues, and the presence of a GPI motif in 19
      of them. We also identified 66 "atypical" cell wall proteins that lack the above
      mentioned characteristics. After tryptic removal of the most accessible proteins
      in the cell wall, several of the same expected GPI proteins and the most commonly
      found "atypical" wall proteins were identified. This result suggests that
      proteins are located not only at the cell wall surface, but are embedded within
      the cell wall itself. These results, which include new identified cell wall
      proteins, and comparison of proteins in blastospore and mycelial walls, will help
      to elucidate the C. albicans cell wall architecture.

PMID- 18712766
TI  - Cluster TOF-SIMS imaging: a new light for in situ metabolomics?
AB  - The advent of metal cluster as a primary ion source in the late 1980s, made it
      feasible to probe surfaces for complex organic structures due to a reduced in
      source fragmentation, and opened the door to the direct analysis of biological
      samples. Despite the mass range measurable by TOF-secondary ion MS (SIMS) still
      being rather limited, the information obtained from cells and tissues comes
      together with the technical innovations introduced in the last decade. In this
      article, we give a brief overview of the technique itself and make some emphasis
      on the advances in the last three years in the analysis of biological surfaces,
      particularly those with direct implication in the biomedical field; reviewing
      what kind of information this instrumentation will add to current tool in
      pathology.

PMID- 18712767
TI  - Nonionic detergent phase extraction for the proteomic analysis of heart membrane
      proteins using label-free LC-MS.
AB  - Heart diseases resulting in heart failure are among the leading causes of
      morbidity and mortality in the Western world and can result from either systemic
      disease (e.g., hypertensive heart disease, ischemic heart disease) or specific
      heart muscle disease (e.g., dilated cardiomyopathy/DCM). Subproteome analysis of
      such disease subsets affords a reduction in sample complexity, potentially
      revealing biomarkers of cardiac failure that would otherwise remain undiscovered
      in proteome wide studies. Label-free nanoscale LC-MS has been applied in this
      study to validate a Triton X-114-based phase enrichment method for cardiac
      membrane proteins. Annotation of the subcellular location combined with GRAVY
      score analysis indicates a clear separation between soluble and membrane-bound
      proteins with an enrichment of over 62% for this protein subset. LC-MS allowed
      confident identification and annotation of hydrophobic proteins in this control
      sample pilot study and demonstrates the power of the proposed technique to
      extract integral membrane-bound proteins. This approach should be applicable to a
      wider scale study of disease-associated changes in the cardiac membrane
      subproteome.

PMID- 18712769
TI  - Combination of immunohistochemistry and laser ablation ICP mass spectrometry for
      imaging of cancer biomarkers.
AB  - Laser ablation (LA) ICP-MS has been developed as a new tool for imaging of cancer
      biomarkers in tissue sections. The distribution of two breast cancer-associated
      proteins, MUC-1 and HER2 was studied based on multiple line rastering of tissue
      sections and measurement of relevant Au/Ag tagged antibodies bound to the tissue.
      Comparisons with optical microscopy indicated extremely high sensitivity for the
      LA technique and sufficiently good resolution to permit fine scale feature
      mapping at the cellular level. Application to the quantitative assessment of HER2
      expression in tissue microarrays was demonstrated.

PMID- 18712768
TI  - SIMS and MALDI MS imaging of the spinal cord.
AB  - The application of MS to imaging, or MS imaging (MSI), allows for the direct
      investigation of tissue sections to identify biological compounds and determine
      their spatial distribution. We present an approach to MSI that combines secondary
      ion MS (SIMS) and MALDI MS for the imaging and analysis of rat spinal cord
      sections, thereby enhancing the chemical coverage obtained from an MSI
      experiment. The spinal cord is organized into discrete, anatomically defined
      areas that include motor and sensory networks composed of chemically diverse
      cells. The MSI data presented here reveal the spatial distribution of multiple
      phospholipids, proteins, and neuropeptides obtained within single, 20 mum
      sections of rat spinal cord. Analyte identities are initially determined by
      primary mass match and confirmed in follow-up experiments using LC MS/MS from
      extracts of adjacent spinal cord sections. Additionally, a regional analysis of
      differentially localized signals serves to rapidly screen compounds of varying
      intensities across multiple spinal regions. These MSI analyses reveal new
      insights into the chemical architecture of the spinal cord and set the stage for
      future imaging studies of the chemical changes induced by pain, anesthesia, and
      drug tolerance.

PMID- 18712770
TI  - Time-dependent evolution of tissue markers by MALDI-MS imaging.
AB  - We have used MALDI-MS imaging (MALDI-MSI) to monitor the time dependent
      appearance and loss of signals when tissue slices are brought rapidly to room
      temperature for short to medium periods of time. Sections from mouse brain were
      cut in a cryostat microtome, placed on a MALDI target and allowed to warm to room
      temperature for 30 s to 3 h. Sections were then refrozen, fixed by ethanol
      treatment and analysed by MALDI-MSI. The intensity of a range of markers were
      seen to vary across the time course, both increasing and decreasing, with the
      intensity of some markers changing significantly within 30 s and markers also
      showed tissue location specific evolution. The markers resulting from this
      autolysis were compared directly to those that evolved in a comparable 16 h on
      tissue trypsin digest, and the markers that evolved in the two studies were seen
      to be substantially different. These changes offer an important additional level
      of location-dependent information for mapping changes and seeking disease
      dependent biomarkers in the tissue. They also indicate that considerable care is
      required to allow comparison of biomarkers between MALDI-MSI experiments and also
      has implications for the standard practice of thaw-mounting multiple tissue
      sections onto MALDI-MS targets.

PMID- 18712771
TI  - Direct profiling and identification of peptide expression differences in the
      pancreas of control and ob/ob mice by imaging mass spectrometry.
AB  - Imaging mass spectrometry (IMS) technology utilizes MALDI MS to map molecules of
      interest in thin tissue sections. In this study, we have evaluated the potential
      of MALDI IMS to study peptide expression patterns in the mouse pancreas under
      normal and pathological conditions, and to in situ identify peptides of interest
      using MS/MS. Different regions of the pancreas of both control and ob/ob mice
      were imaged, resulting in peptide-specific profiles. The distribution of ions of
      m/z 3120 and 3439 displayed a striking resemblance with Langerhans islet's
      histology and, following MS/MS fragmentation and database searching were
      identified as C-peptide of insulin and glicentin-related polypeptide,
      respectively. In addition, a significant increase of the 3120 peak intensity in
      the obese mice was observed. This study underscores the potential of MALDI IMS to
      study the contribution of peptides to pancreas pathology.

PMID- 18712772
TI  - Protein and peptides in pictures: imaging with MALDI mass spectrometry.
AB  - Imaging using MS has the potential to deliver highly parallel, multiplexed data
      on the specific localization of molecular ions in tissue samples directly, and to
      measure and map the variations of these ions during development and disease
      progression or treatment. There is an intrinsic potential to be able to identify
      the biomarkers in the same experiment, or by relatively simple extension of the
      technique. Unlike many other imaging techniques, no a priori knowledge of the
      markers being sought is necessary. This review concentrates on the use of MALDI
      MS for MS imaging (MSI) of proteins and peptides, with an emphasis on mammalian
      tissue. We discuss the methodologies used, their potential limitations, overall
      experimental considerations and progress that has been made towards establishing
      MALDI-MSI as a routine technique for the spatially resolved measurement of
      peptides and proteins. As well as determining the local abundance of individual
      molecular ions, there is the potential to determine their identity within the
      same experiment using relatively simple extensions of the basic techniques. In
      this way MSI offers an important opportunity for biomarker discovery and
      identification.

PMID- 18712773
TI  - Perturbation of the chromosomal binding of RCC1, Mad2 and survivin causes spindle
      assembly defects and mitotic catastrophe.
AB  - Mitotic catastrophe is a form of cell death that results from aberrant mitosis.
      Currently, the mechanisms involved in this form of cell death remain poorly
      understood. We found that actinomycin D induces mitotic catastrophe with severe
      spindle assembly defects. We have studied the nature of three groups of
      chromosome binding proteins in mitotic cells treated with actinomycin D. We found
      that actinomycin D reduced the binding affinity of RCC1 to the mitotic
      chromosome, which led to a reduction of RanGTP level. In addition, Mad2 was not
      concentrated at the kinetochores, indicating that the mitotic spindle checkpoint
      was affected. Furthermore, the localization of survivin was altered in cells.
      These data suggested that chromosomal binding of the mitotic regulators such as
      RCC1, Mad2 and survivin is essential for mitotic progression. Mitotic chromosomes
      not only carry the genetic material needed for the newly synthesized daughter
      cells, but also serve as docking sites for some of the mitotic regulators.
      Perturbation of their binding to the mitotic chromosome by actinomycin D could
      affect their functions in regulating mitotic progression thus leading to severe
      spindle defects and mitotic catastrophe.

PMID- 18712775
TI  - Nuclear receptor cofactor receptor interacting protein 140 controls hepatic
      triglyceride metabolism during wasting in mice.
AB  - In mammals, triglycerides (TG) represent the most concentrated form of energy.
      Aberrant TG storage and availability are intimately linked to the negative energy
      balance under severe clinical conditions, such as starvation, sepsis, or cancer
      cachexia. Despite its crucial role for energy homeostasis, molecular key
      determinants of TG metabolism remain enigmatic. Here we show that the expression
      of nuclear receptor cofactor receptor interacting protein (RIP) 140 was induced
      in livers of starved, septic, and tumor-bearing mice. Liver-specific knockdown of
      RIP140 led to increased hepatic TG release and alleviated hepatic steatosis in
      tumor-bearing, cachectic animals. Indeed, hepatic RIP140 was found to control the
      expression of lipid-metabolizing genes in liver. CONCLUSION: By preventing the
      mobilization of hepatic TG stores, the induction of RIP140 in liver provides a
      molecular rationale for hepatic steatosis in starvation, sepsis, or cancer
      cachexia. Inhibition of hepatic RIP140 transcriptional activity might, thereby,
      provide an attractive adjunct scheme in the treatment of these conditions.

PMID- 18712774
TI  - Lopinavir impairs protein synthesis and induces eEF2 phosphorylation via the
      activation of AMP-activated protein kinase.
AB  - HIV anti-retroviral drugs decrease protein synthesis, although the underlying
      regulatory mechanisms of this process are not fully established. Therefore, we
      investigated the effects of the HIV protease inhibitor lopinavir (LPV) on protein
      metabolism. We also characterized the mechanisms that mediate the effects of this
      drug on elongation factor-2 (eEF2), a key component of the translational
      machinery. Treatment of C2C12 myocytes with LPV produced a dose-dependent
      inhibitory effect on protein synthesis. This effect was observed at 15 min and
      was maintained for at least 4 h. Mechanistically, LPV increased the
      phosphorylation of eEF2 and thereby decreased the activity of this protein.
      Increased phosphorylation of eEF2 was associated with increased activity of its
      upstream regulators AMP-activated protein kinase (AMPK) and eEF2 kinase (eEF2K).
      Both AMPK and eEF2K directly phosphorylated eEF2 in an in vitro kinase assay
      suggesting two distinct paths lead to eEF2 phosphorylation. To verify this
      connection, myocytes were treated with the AMPK inhibitor compound C. Compound C
      blocked eEF2K and eEF2 phosphorylation, demonstrating that LPV affects eEF2
      activity via an AMPK-eEF2K dependent pathway. In contrast, incubation of myocytes
      with rottlerin suppressed eEF2K, but not eEF2 phosphorylation, suggesting that
      eEF2 can be regulated independent of eEF2K. Finally, LPV did not affect PP2A
      activity when either eEF2 or peptide was used as the substrate. Collectively,
      these results indicate that LPV decreases protein synthesis, at least in part,
      via inhibition of eEF2. This appears regulated by AMPK which can act directly on
      eEF2 or indirectly via the action of eEF2K.

PMID- 18712776
TI  - Regaining power lost by non-compliance via full probability modelling.
AB  - Non-compliance, or non-receipt of randomized intervention, is a common problem in
      randomized controlled trials. An intention-to-treat (ITT) analysis, which
      compares individuals as randomized, under-estimates the efficacy of the
      intervention and leads to a loss of power. We explore the possibility of
      regaining some of this power in a setting with all-or-nothing compliance, without
      making any assumptions about the comparability of compliers and non-compliers.
      Efficacy may be specified as the complier average causal effect (CACE), which is
      the difference in mean outcome among compliers. Compliance is only partially
      observed, but under an exclusion restriction assumption, the CACE may be
      estimated using maximum likelihood. In order to quantify the possible gain in
      power, we derive an expression for the asymptotic relative efficiency (ARE) of
      the CACE relative to the ITT effect with a Normally distributed outcome. Under
      the assumption of a common CACE across covariate strata, the CACE estimate is at
      least as powerful as ITT analysis. The inclusion of covariates that predict
      compliance enables an additional gain in power, which is investigated
      algebraically. Using data from three clinical trials, we obtain values of the ARE
      ranging up to 1.05 due to covariates alone, and 1.13 due to CACE modelling alone,
      corresponding to gains in power of up to 5 per cent. This implies that a large
      gain in power obtained using as-treated or per-protocol analyses is likely to be
      due to the strong and often implausible assumptions such analyses require to be
      valid.

PMID- 18712777
TI  - Evaluation of a method for fitting a semi-Markov process model in the presence of
      left-censored spells using the Cardiovascular Health Study.
AB  - We used a longitudinal data set covering 13 years from the Cardiovascular Health
      Study to evaluate the properties of a recently developed approach to deal with
      left censoring that fits a semi-Markov process (SMP) model by using an analog to
      the stochastic EM algorithm--the SMP-EM approach. It appears that the SMP-EM
      approach gives estimates of duration-dependent probabilities of health changes
      similar to those obtained by using SMP models that have the advantage of actual
      duration data. SMP-EM estimates of duration-dependent transition probabilities
      also appear more accurate and less variable than multi-state life table
      estimates.

PMID- 18712778
TI  - Evaluating spatial methods for investigating global clustering and cluster
      detection of cancer cases.
AB  - There have been articles on comparing methods for global clustering evaluation
      and cluster detection in disease surveillance, but power and sample size (SS)
      requirements have not been explored for spatially correlated data in this area.
      We are developing such requirements for tests of spatial clustering and cluster
      detection for regional cancer cases. We compared global clustering methods
      including Moran's I, Tango's and Besag-Newell's R statistics, and cluster
      detection methods including circular and elliptic spatial scan statistics
      (SaTScan), flexibly shaped spatial scan statistics, Turnbull's cluster evaluation
      permutation procedure, local indicators of spatial association, and upper-level
      set scan statistics. We identified eight geographic patterns that are
      representative of patterns of mortality due to various types of cancer in the
      U.S. from 1998 to 2002. We then evaluated the selected spatial methods based on
      state- and county-level data simulated from these different spatial patterns in
      terms of geographic locations and relative risks, and varying SSs using the 2000
      population in each county. The comparison provides insight into the performance
      of the spatial methods when applied to varying cancer count data in terms of
      power and precision of cluster detection.

PMID- 18712779
TI  - Analyses of cumulative incidence functions via non-parametric multiple
      imputation.
AB  - We describe a non-parametric multiple imputation method that recovers the missing
      potential censoring information from competing risks failure times for the
      analysis of cumulative incidence functions. The method can be applied in the
      settings of stratified analyses, time-varying covariates, weighted analysis of
      case-cohort samples and clustered survival data analysis, where no current
      available methods can be readily implemented. The method uses a Kaplan-Meier
      imputation method for the censoring times to form an imputed data set, so
      cumulative incidence can be analyzed using techniques and software developed for
      ordinary right censored survival data. We discuss the methodology and show from
      both simulations and real data examples that the method yields valid estimates
      and performs well. The method can be easily implemented via available software
      with a minor programming requirement (for the imputation step). It provides a
      practical, alternative analysis tool for otherwise complicated analyses of
      cumulative incidence of competing risks data.

PMID- 18712780
TI  - Comments on 'Sample size evaluation for a multiply matched case-control study
      using the score test from a conditional logistic (discrete Cox PH) regression
      model' by J. M. Lachin, Statistics in Medicine 2008; 27(14):2509-2523.

PMID- 18712781
TI  - Checking hazard regression models using pseudo-observations.
AB  - Graphical methods for model diagnostics are an essential part of the model
      fitting procedure. However, in survival analysis, the plotting is always hampered
      by the presence of censoring. Although model specific solutions do exist and are
      commonly used, we present a more general approach that covers all the models
      using the same framework. The pseudo-observations enable us to calculate
      residuals for each individual at each time point regardless of censoring and
      provide methods for simultaneously checking all the assumptions of both the Cox
      and the additive model. We introduce methods for single as well as multiple
      covariate cases and complement them with corresponding goodness-of-fit tests. The
      methods are illustrated on simulated as well as real data examples.

PMID- 18712782
TI  - Testing linkage disequilibrium from pooled DNA: a contingency table perspective.
AB  - Pooling DNA samples of multiple individuals has been advocated as a method to
      reduce genotyping costs. Under such a scheme, only the allele counts at each
      locus, not the haplotype information, are observed. We develop a systematic way
      for handling such data by formulating the problem in terms of contingency tables,
      where pooled allele counts are expressed as the margins and the haplotype counts
      correspond to the unobserved cell counts. We show that the cell frequencies can
      be uniquely determined from the marginal frequencies under the usual Hardy
      Weinberg equilibrium (HWE) assumption and that the maximum likelihood estimates
      of haplotype frequencies are consistent and asymptotically normal as the number
      of pools increases. The limiting covariance matrix is shown to be closely related
      to the extended hypergeometric distribution. Our results are used to derive Wald
      type tests for linkage disequilibrium (LD) coefficient using pooled data. It is
      discovered that pooling is not efficient in testing weak LD despite its
      efficiency in estimating haplotype frequencies. We also show by simulations that
      the proposed LD tests are robust to slight deviation from HWE and to minor
      genotype error. Applications to two real angiotensinogen gene data sets are also
      provided.

PMID- 18712783
TI  - The vesicular integral protein-like gene is essential for development of a
      mechanosensory system in zebrafish.
AB  - The zebrafish hi472 mutation is caused by a retroviral insertion into the
      vesicular integral protein-like gene, or zVIPL, a poorly studied lectin
      implicated in endoplasmic reticulum (ER)-Golgi trafficking. A mutation in the
      shorter isoform of zVIPL (zVIPL-s) results in a reduction of mechanosensitivity
      and consequent loss of escape behavior. Here we show that motoneurons and
      hindbrain reticulospinal neurons, which normally integrate mechanosensory inputs,
      failed to fire in response to tactile stimuli in hi472 larvae, suggesting a
      perturbation in sensory function. The hi472 mutant larvae in fact suffered from a
      severe loss of functional neuromasts of the lateral line mechanosensory system, a
      reduction of zVIPL labeling in support cells, and a reduction or even a complete
      loss of hair cells in neuromasts. The Delta-Notch signaling pathway is implicated
      in cellular differentiation of neuromasts, and we observed an increase in Notch
      expression in neuromasts of hi472 mutant larvae. Treatment of hi472 mutant larvae
      with DAPT, an inhibitor of Notch signaling, or overexpression of the Notch ligand
      deltaB in hi472 mutant blastocysts produced partial rescue of the morphological
      defects and of the startle response behavior. We conclude that zVIPL-s is a
      necessary component of Delta-Notch signaling during neuromast development in the
      lateral line mechanosensory system.

PMID- 18712784
TI  - Distribution of progesterone receptor immunoreactivity in the midbrain and
      hindbrain of postnatal rats.
AB  - Nuclear steroid hormone receptors are powerful transcription factors and
      therefore have the potential to influence and regulate fundamental processes of
      neural development. The expression of progesterone receptors (PR) has been
      described in the developing forebrain of rats and mice, and the mammalian brain
      may be exposed to significant amounts of progesterone, either from maternal
      sources and/or de novo synthesis of progesterone from cholesterol within the
      brain. The present study examined the distribution of PR immunoreactive (PRir)
      cells within the midbrain and hindbrain of postnatal rats. The results
      demonstrate that PR is transiently expressed within the first 2 weeks of life in
      specific motor, sensory and reticular core nuclei as well as within midbrain
      dopaminergic cell groups such as the substantia nigra and the ventral tegmental
      area. Additionally, robust PRir was observed in cells of the lower rhombic lip, a
      transient structure giving rise to precerebellar nuclei. These results suggest
      that progestins and progesterone receptors may play a fundamental role in the
      postnatal development of numerous midbrain and hindbrain nuclei, including some
      areas implicated in human disorders. Additionally, these findings contribute to
      the increasing evidence that steroid hormones and their receptors influence
      neural development in a wide range of brain areas, including many not typically
      associated with reproduction or neuroendocrine function.

PMID- 18712785
TI  - Murine cirrhosis induces hepatocyte epithelial mesenchymal transition and
      alterations in survival signaling pathways.
AB  - Hepatocytes that reside in a chronically-injured liver have altered growth
      responses compared to hepatocytes in normal liver. Transforming growth factor
      beta (TGFbeta) is upregulated in the cirrhotic liver, and cirrhotic hepatocytes,
      unlike normal hepatocytes exposed to this cytokine, exhibit decreased apoptosis.
      In fetal hepatocytes, TGFbeta also induces epithelial-mesenchymal transition
      (EMT) and signaling changes in cell survival pathways. Here, chronic murine liver
      injury was induced by twice-weekly carbon tetrachloride administration for 8
      weeks. Normal liver-derived hepatocytes (NLDH) and cirrhotic liver-derived
      hepatocytes (CLDH) were examined for EMT and the small mothers against
      decapentaplegic homolog (Smad), phosphatidylinositol-3-kinase (PI3K/Akt), and
      mitogen activated protein kinase (MAPK) pathways were investigated.
      Immunofluorescence imaging of cirrhotic livers demonstrated increased vimentin
      expression, which was confirmed by immunoblot analysis. In vitro, CLDH exhibited
      increased vimentin and type 1 collagen expression within cellular extensions
      consistent with EMT. Treatment with TGFbeta augmented the EMT response in CLDH.
      In contrast, untreated NLDH did not display features of EMT but responded to
      TGFbeta with increased vimentin expression and EMT characteristics. In response
      to PI3K/Akt inhibition, CLDH had decreased basal and insulin-stimulated p-Akt
      expression and decreased apoptosis compared to NLDH. In both NLDH and CLDH,
      vimentin expression was dependent on PI3K/Akt activity. CLDH demonstrated
      increased basal p-extracellular signal-regulated kinase expression that was
      independent of Smad and PI3K/Akt signaling. Inhibition of the MAPK pathway
      produced a marked increase in CLDH apoptosis. CONCLUSION: CLDH have increased
      vimentin and type 1 collagen expression and morphologic features consistent with
      EMT. In addition, compared to NLDH, the cellular signaling phenotype of CLDH
      changes from a MAPK-independent pathway to a MAPK-dependent cell survival
      pathway. These findings may have clinical implications for chemoprevention of
      hepatocellular carcinoma in the cirrhotic liver.

PMID- 18712786
TI  - Clonal expansions of 6-thioguanine resistant T lymphocytes in the blood and tumor
      of melanoma patients.
AB  - The identification of specific lymphocyte populations that mediate tumor immune
      responses is required for elucidating the mechanisms underlying these responses
      and facilitating therapeutic interventions in humans with cancer. To this end,
      mutant hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficient (HPRT-) T
      cells were used as probes to detect T-cell clonal amplifications and trafficking
      in vivo in patients with advanced melanoma. Mutant T-cells from peripheral blood
      were obtained as clonal isolates or in mass cultures in the presence of 6
      thioguanine (TG) selection and from tumor-bearing lymph nodes (LNs) or metastatic
      melanoma tissues by TG-selected mass cultures. Nonmutant (wild-type) cells were
      obtained from all sites by analogous means, but without TG selection. cDNA
      sequences of the T-cell receptor (TCR) beta chains (TCR-beta), determined
      directly (clonal isolates) or following insertion into plasmids (mass cultures),
      were used as unambiguous biomarkers of in vivo clonality of mature T-cell clones.
      Clonal amplifications, identified as repetitive TCR-beta V-region,
      complementarity determining region 3 (CDR3), and J-region gene sequences, were
      demonstrated at all sites studied, that is, peripheral blood, LNs, and metastatic
      tumors. Amplifications were significantly enriched among the mutant compared with
      the wild-type T-cell fractions. Importantly, T-cell trafficking was manifested by
      identical TCR-beta cDNA sequences, including the hypervariable CDR3 motifs, being
      found in both blood and tissues in individual patients. The findings described
      herein indicate that the mutant T-cell fractions from melanoma patients are
      enriched for proliferating T-cells that infiltrate the tumor, making them
      candidates for investigations of potentially protective immunological responses.

PMID- 18712787
TI  - Chromosome aberrations in peripheral blood lymphocytes of high-risk HPV-infected
      women with HGSIL.
AB  - Genomic instability is one of the main characteristics of malignant tumors,
      including HPV-induced cervical cancer. The aim of this study was to explore the
      use of assessing chromosome aberrations (CA) in peripheral blood lymphocytes as a
      biomarker for genomic instability in high-risk HPV-infected women with high-grade
      squamous intraepithelial lesions (HGSIL). A total of 120 women were recruited for
      this study, following cytology/colposcopy evaluation and HPV DNA detection. The
      study groups consisted of 30 HPV(+) women with histologically confirmed cervical
      intraepithelial neoplasia grade 2/3 and 30 HPV(+) women with carcinoma in situ
      (CIS). Two control groups, including 30 women HPV(-) and 30 women HPV(+), were
      recruited among women who were reported as cytology negative. Lymphocyte cell
      cultures were established for 52 hr, and 100 complete metaphase cells were
      evaluated per subject for CA analysis. The results show that women with CIS had
      significantly higher frequencies of both aneuploidy (0.67 +/- 0.20 vs. 0.14 +/-
      0.08, P = 0.020) and tetraploidy (0.88 +/- 0.23 vs. 0.17 +/- 0.08, P = 0.013) in
      comparison with HPV(-) controls. These findings suggest the usefulness of
      peripheral blood lymphocytes to detect genomic instability associated with HPV
      induced HGSIL.

PMID- 18712789
TI  - Kinesin-5 is not essential for mitotic spindle elongation in Dictyostelium.
AB  - The proper assembly and operation of the mitotic spindle is essential to ensure
      the accurate segregation of chromosomes and to position the cytokinetic furrow
      during cell division in eukaryotes. Not only are dynamic microtubules required
      but also the concerted actions of multiple motor proteins are necessary to effect
      spindle pole separation, chromosome alignment, chromatid segregation, and spindle
      elongation. Although a number of motor proteins are known to play a role in
      mitosis, there remains a limited understanding of their full range of functions
      and the details by which they interact with other spindle components. The kinesin
      5 (BimC/Eg5) family of motors is largely considered essential to drive spindle
      pole separation during the initial and latter stages of mitosis. We have deleted
      the gene encoding the kinesin-5 member in Dictyostelium, (kif13), and find that,
      in sharp contrast with results found in vertebrate, fly, and yeast organisms,
      kif13(-) cells continue to grow at rates indistinguishable from wild type.
      Phenotype analysis reveals a slight increase in spindle elongation rates in the
      absence of Kif13. More importantly, there is a dramatic, premature separation of
      spindle halves in kif13(-) cells, suggesting a novel role of this motor in
      maintaining spindle integrity at the terminal stages of division.

PMID- 18712790
TI  - ISTA13--international interlaboratory comparative evaluation of microbial assay
      for risk assessment (MARA).
AB  - The microbial assay for risk assessment (MARA) is an innovative system based on
      an array of 11 different microbial species freeze-dried in a 96-well micro-titer
      plate. Developed for testing the toxicity of chemicals, mixtures, and
      environmental samples, the assay employs species of a taxonomically diverse
      range. In addition to 10 prokaryotic species, a eukaryote (yeast) is included in
      the range. The MARA's innate scope of a multi-dimensional test allows
      determination of toxicity based on a unique assay fingerprint or index,
      numerically expressed as the mean microbial toxic concentration (MTC). The most
      significant potential of the test is in the additional inference that can be
      conveyed to the toxicity evaluation because of the presence of each of the
      constituent species. The performance of MARA was evaluated to ascertain its
      capability and potential scope in an intralaboratory trial. Sensitivity to
      toxicants and different environmental samples was assessed. Evaluation included
      comparison with other tests; namely Microtox, invertebrate (Daphnia magna and
      Thamnocephalus platyurus) microbiotests, and respiration- and nitrification
      inhibition tests. MARA's performance was further assessed with the implementation
      of an international interlaboratory trial. This involved the participation of 13
      laboratories ranging from academic establishments to regulatory agencies. The
      results of the testing will be presented with assessment of the extent of
      variability and specific assay components. The trial evaluation indicated that
      performance of the assay was satisfactory and the results were within the
      acceptable range. MARA is a robust multispecies assay offering scope for toxicity
      assessment of a diverse range of samples.

PMID- 18712788
TI  - Mechanism of T cell tolerance induction by murine hepatic Kupffer cells.
AB  - The liver is known to favor the induction of immunological tolerance rather than
      immunity. Although Kupffer cells (KC) have been indicated to play a role in liver
      tolerance to allografts and soluble antigens, the mechanisms involved remain
      unclear. We hypothesized that KCs could promote immune tolerance by acting as
      incompetent antigen-presenting cells (APC), as well as actively suppressing T
      cell activation induced by other potent APCs. The expression of antigen
      presentation-related molecules by KCs was phenotyped by flow cytometry. The
      abilities of KCs to act as APCs and to suppress T cell activation induced by
      splenic dendritic cells (DC) were examined by in vitro proliferation assays using
      CD4(+) OVA-TCR (ovalbumin T cell receptor) transgenic T cells. We found that,
      compared with DCs, KCs expressed significantly lower levels of major
      histocompatibility complex (MHC) II, B7-1, B7-2, and CD40. This result is
      consistent with our observation that KCs were not as potent as DCs in eliciting
      OVA-specific T cell proliferation. However, KCs isolated from
      polyinosinic:polycytidylic acid-treated mice expressed significantly higher
      levels of MHC II and costimulatory molecules than did naive KCs and could
      stimulate stronger T cell responses. More importantly, we found that KCs could
      inhibit DC-induced OVA-specific T cell activation. Further investigation of the
      underlying mechanism revealed that prostaglandins produced by KCs played an
      important role. The results ruled out the possible involvement of interleukin-10,
      nitric oxide, 2,3-dioxygenase, and transforming growth factor beta in KC-mediated
      T cell suppression. CONCLUSION: Our data indicate that KCs are a tolerogenic APC
      population within the liver. These findings suggest that KCs may play a critical
      role in regulating immune reactions within the liver and contributing to liver
      mediated systemic immune tolerance. (HEPATOLOGY 2008.).

PMID- 18712791
TI  - Selection of high-avidity CD8 T cells correlates with control of hepatitis C
      virus infection.
AB  - Both strong antigenic avidity and acquisition of proper effector functions
      contribute to the efficacy of antiviral T cell responses. To correlate these
      parameters with the outcome of hepatitis C virus (HCV) infection, we
      characterized HCV-specific CD8 T cell lines isolated after immunomagnetic sorting
      of peripheral blood mononuclear cells from human leukocyte antigen A*02 (HLA
      A*02) individuals with various HCV serological statuses, using recombinant HLA
      A*0201 multimers loaded with three immunodominant HCV genotype 1-derived
      epitopes. CD8 T cells specific for these three epitopes were derived from most
      HLA-A*0201 individuals, regardless of their HCV serology or clinical outcome.
      Donors recovered from genotype 1 HCV infection were enriched for high-avidity T
      cells with enhanced interferon gamma (IFN-gamma), tumor necrosis factor alpha,
      and cytotoxic T lymphocyte responses, when compared with seronegative donors and
      seropositive patients infected with irrelevant HCV genotypes. Patients
      chronically infected with genotype 1 strain yielded almost exclusively low
      avidity T cells, whose hyporesponsiveness was primarily attributable to low T
      cell receptor (TCR) avidity rather than intrinsic functional defects. CONCLUSION:
      This study suggests that strong IFN-gamma responses associated with efficient
      viral clearance primarily result from Ag-driven selection/survival of HCV
      specific T cells expressing high-avidity TCR. It also suggests a link between the
      quality of the initial HCV-specific T cell repertoire and susceptibility to
      chronic infection.

PMID- 18712793
TI  - Journal clubs and case conferences: from academic tradition to communities of
      practice.
AB  - INTRODUCTION: As small group learning sessions, Journal Clubs (JCs) and Case
      Conferences (CCs), if structured interactively, have potential as educational
      formats that can change practice. However, the degree to which these formats, as
      currently typically structured, lead to practice change is unknown. METHODS: We
      used concepts of communities of practice (COPs) to structure JCs and CCs. We
      conducted an observational descriptive study of the learnings, implemented
      learnings, and barriers to implementing learnings identified in JC and CC
      sessions conducted in 2005-2006. RESULTS: Two hundred learnings in 10 different
      categories emerged from 73 JC or CC sessions. By self-report, over half of
      identified learnings were implemented in practice; 60 barriers to implementing
      learnings (8 different categories) were also identified. Patterns of learnings,
      implemented learnings, and barriers varied among sessions. DISCUSSION: JCs and
      CCs can be structured with explicit intent to articulate learnings and facilitate
      implementation of learnings in practice. Further work is needed to validate the
      learning and barrier categories we identified, objectively verify short- and
      longer-term practice outcomes, explore the role of JCs and CCs in addressing
      barriers to learning, and facilitate sustainability of learning in practice.

PMID- 18712792
TI  - Hepatitis C virus JFH-1 strain infection in chimpanzees is associated with low
      pathogenicity and emergence of an adaptive mutation.
AB  - The identification of the hepatitis C virus (HCV) strain JFH-1 enabled the
      successful development of infectious cell culture systems. Although this strain
      replicates efficiently and produces infectious virus in cell culture, the
      replication capacity and pathogenesis in vivo are still undefined. To assess the
      in vivo phenotype of the JFH-1 virus, cell culture-generated JFH-1 virus (JFH
      1cc) and patient serum from which JFH-1 was isolated were inoculated into
      chimpanzees. Both animals became HCV RNA-positive 3 days after inoculation but
      showed low-level viremia and no evidence of hepatitis. HCV viremia persisted 8
      and 34 weeks in JFH-1cc and patient serum-infected chimpanzees, respectively.
      Immunological analysis revealed that HCV-specific immune responses were similarly
      induced in both animals. Sequencing of HCV at various times of infection
      indicated more substitutions in the patient serum-inoculated chimpanzee, and the
      higher level of sequence variations seemed to be associated with a prolonged
      infection in this animal. A common mutation G838R in the NS2 region emerged early
      in both chimpanzees. This mutation enhances viral assembly, leading to an
      increase in viral production in transfected or infected cells. CONCLUSION: Our
      study shows that the HCV JFH-1 strain causes attenuated infection and low
      pathogenicity in chimpanzees and is capable of adapting in vivo with a unique
      mutation conferring an enhanced replicative phenotype.

PMID- 18712794
TI  - Structured intervention utilizing state professional societies to foster quality
      improvement in practice.
AB  - INTRODUCTION: Despite the existence of guidelines for attention deficit
      hyperactivity disorder (ADHD), clinical practices vary substantially.
      Practitioners can apply quality improvement (QI) strategies to adapt office
      processes and clinical practice towards evidence-based care. We identified
      facilitators and barriers to participation in a professional society-led
      structured collaborative to learn QI methods and improve care. METHODS: Ten
      chapters of the American Academy of Pediatrics participated in the effort.
      Support to chapter leaders included conference calls, listserv, technical
      support, and data aggregation. Support from the chapters to participating
      pediatricians included online continuing medical education modules, a workshop,
      chart reviews, and QI coaching. Qualitative data were obtained through interviews
      of 22 project leaders and reviews of project progress reports. Quantitative
      results were obtained from surveys of 186 physician participants. Outcomes
      included facilitators/barriers to program implementation, evidence for sustained
      chapter QI infrastructure, and participant assessment of improvements in care.
      RESULTS: Facilitators included physician opinion leaders, a workshop, conference
      calls, QI support, and opportunities for shared learning. Barriers included lack
      of time, competing clinical priorities, challenges of using the online module,
      and underutilization of listservs. Seven chapters planned ongoing activities
      around attention deficit hyperactivity disorder (ADHD), eight had specific plans
      to use QI infrastructure for additional clinical topics, and three developed
      significant QI infrastructure. Physicians believed care improved. DISCUSSION: As
      requirements grow for participation in QI for maintenance of certification,
      national and state-level professional societies are interested in and can develop
      infrastructure to support quality improvement. Coaching, tools, and support from
      the national organization and QI experts are helpful in facilitating efforts.

PMID- 18712795
TI  - After the crash: research-based theater for knowledge transfer.
AB  - INTRODUCTION: The aim of this project was to develop and evaluate a research
      based dramatic production for the purpose of transferring knowledge about
      traumatic brain injury (TBI) to health care professionals, managers, and decision
      makers. METHODS: Using results drawn from six focus group discussions with key
      stakeholders (consumers, informal caregivers, and health care practitioners
      experienced in the field of TBI) and relevant scientific literature, a 50-minute
      play was produced for the purpose of conveying the experiences of TBI survivors,
      informal care providers, and health practitioners and best practice for TBI care.
      A self-administered postperformance survey was distributed to audience members at
      the end of four performances in Ontario, Canada, to evaluate the play's efficacy.
      Two hundred ninety-one questionnaires were completed. The questionnaire had five
      questions scored on a 5-item Likert scale with space for open-ended comments.
      RESULTS: Consistently high mean scores from the questionnaires indicate that
      theater is a highly efficacious and engaging method of knowledge transfer,
      particularly for complex material that deals with human emotion and interpersonal
      relationships. DISCUSSION: Responses supported the effectiveness of drama as a
      knowledge translation strategy and identified its potential to impact practice
      positively.

PMID- 18712796
TI  - Development of an asset map of medical education research activity.
AB  - INTRODUCTION: Medical education research is gaining recognition as scholarship
      within academic medical centers. This survey was conducted at a medium-sized
      academic medical center in the United States. The purpose of the study was to
      learn faculty interest in research in medical education, so assets could be used
      to develop educational scholarship further. METHODS: A cross-sectional study
      design was used to survey faculty activity and interest in medical education
      research at Wake Forest University School of Medicine (WFUSM). RESULTS: Overall
      response rate was 31% (263 out of 855) of faculty. Over half (60%) indicated
      interest in education research with 18% of the respondents currently involved in
      education research. If faculty were aware that education scholarship can lead to
      advancement, they were more likely to be involved in conducting such research ( p
      < 0.01). A total of 22% did not understand what was meant by education research
      and 17% had no interest in education research. DISCUSSION: Interest in medical
      education research and scholarship is evident at WFUSM. Experience in conducting
      education research and understanding of the nature of this type of research have
      not yet been fully developed. There appears to be a core set of faculty
      interested in conducting education research who may serve as a resource for
      faculty development in future medical education scholarship.

PMID- 18712798
TI  - Learning to collaborate: a case study of performance improvement CME.
AB  - INTRODUCTION: Performance Improvement Continuing Medical Education (PI CME) is a
      mechanism for joining quality improvement (QI) in health care to continuing
      medical education (CME) systems together. Although QI practices and CME
      approaches have been recognized for years, what emerges from their integration is
      largely unfamiliar, because it requires the collaboration of CME providers and
      stakeholders within the health care systems who traditionally have not worked
      together and may not have the same understanding of QI issues to close
      performance gaps. This study describes how an academic institution and a
      community-based primary care practice collaborated to enhance patient care in the
      area of hypertension. It offers lessons learned from a PI CME activity in the
      area of hypertension. METHODS: This was an observational case study. Data were
      collected through interviews, observations of educational events, and review of
      documents such as learning logs, which were designed to: (1) help physicians
      learn and change, (2) satisfy requirements for CME credit, (3) serve as the basis
      for reimbursement, and (4) provide data for the case study. RESULTS: Nine
      clinicians from one clinic completed the PI CME activity, achieved measurable
      improvements in their practice, and contributed to systems change. The study
      highlighted (1) the value of shared goals and agreement on the process among the
      participants, planners, and others involved; (2) the advantage of a
      multidisciplinary approach; (3) the importance of supporting clinicians'
      continuing motivation to participate; and (4) the need to allow sufficient time
      to enable the initiative to evolve. DISCUSSION: PI CME required unprecedented
      collaboration between CME planners and QI stakeholders to enable change in
      clinical practice.

PMID- 18712799
TI  - Barriers to innovation in continuing medical education.
AB  - INTRODUCTION: Criteria for maintenance of certification (MOC) emphasize the
      importance of competencies such as communication, professionalism, systems-based
      care, and practice performance in addition to medical knowledge. Success of this
      new competency paradigm is dependent on physicians' willingness to engage in
      activities that focus on less traditional competencies. We undertook this
      analysis to determine whether physicians' preferences for CME are barriers to
      participation in innovative programs. METHODS: A geographically stratified,
      random sample of 755 licensed, practicing physicians in the state of Oregon were
      surveyed regarding their preferences for type of CME offering and instructional
      method and plans to recertify. RESULTS: Three hundred seventy-six of 755 surveys
      were returned for +/-5% margin of error at 95% confidence level; 91% of
      respondents were board certified. Traditional types of CME offerings and
      instructional methods were preferred by the majority of physicians. Academic
      physicians were less likely than clinical physicians to prefer nontraditional
      types of CME offerings and instructional methods. Multiple regression analyses
      did not reveal any significant differences based on demography, practice
      location, or physician practice type. DISCUSSION: Physicians who participate in
      CME select educational opportunities that appeal to them. There is little
      attraction to competency-based educational activities despite their requirement
      for MOC. The apparent disparity between the instructional methods a learner
      prefers and those that are the most effective in changing physician behavior may
      represent a barrier to participating in more innovative CME offerings and
      instructional methods. These findings are important for medical educators and CME
      program planners developing programs that integrate studied and effective
      educational methods into CME programs that are attractive to physicians.

PMID- 18712800
TI  - Functional mentoring: a practical approach with multilevel outcomes.
AB  - INTRODUCTION: Mentoring is a central component of professional development.
      Evaluation of "successful" mentoring programs, however, has been limited and
      mainly focused on measures of satisfaction with the relationship. In today's
      environment, mentoring programs must produce tangible outcomes to demonstrate
      success. To address this issue, the authors advance the framework of functional
      mentoring combined with measurement of outcomes at multiple levels. METHODS: The
      mentoring program is embedded within an intensive, continuing medical education
      (CME) accredited faculty development program. Survey methodology is used to
      collect qualitative and quantitative data at the start, midpoint, and end of the
      program and longitudinally. Participants in 4 years of the program were surveyed.
      RESULTS: In 4 years, 165 faculty participated in the program. Respondents were
      highly satisfied with the pairings: 85% of junior faculty believed their mentor
      had a significant effect on their projects. Junior faculty reported a significant
      enhancement of skills related to initiating and negotiating a new mentoring
      relationship (85%) and stated that their project would have a significant impact
      on their career (92%) and on the department or institution (86%). DISCUSSION: The
      success of this mentoring program is demonstrated at multiple levels. The key
      outcome of functional mentoring is the project. Projects are aligned with
      professional responsibilities and with institutional missions. The project
      contributes to the individual's dossier and adds value to the institution.
      Functional mentoring is a practical approach that allows measurable results at
      multiple levels.

PMID- 18712801
TI  - Social interaction and participation: formative evaluation of online CME modules.
AB  - INTRODUCTION: This exploratory study examines Canadian physicians' participation
      in online social activities and learning discussions, perceptions of online
      social closeness, barriers and motivators to participation, and perceptions of
      the impact of course duration and face-to-face meetings on learning. METHODS:
      Formative evaluations were administrated to physicians participating in two
      online continuing medical education (CME) courses. Responses were recorded and
      calculated by the Blackboard Learning System. Content analysis was used to
      categorize comments and identify influencing factors. Online postings were
      counted to measure participation in the learning activities. RESULTS: The
      participation rate of 158 physicians and 10 facilitators in online social
      activities was very low. Forty-five percent of responding participants reported
      that more time for discussion would help them learn more; 62% stated that the
      initial face-to-face meeting helped improve online social relations and increase
      peer interactions online. Thirty-five percent of respondents reported
      participating in online social activities, while 29% had no time to do so, and
      18% were not interested in doing so. Thirty-five percent felt closer or more
      connected to their peers after two discussion sessions; 11% did not feel closer
      because of their low participation; and 16% did not feel closer because of
      inadequate peer interaction. On the two evaluations, 49% and 22% of respondents,
      respectively, perceived lack of time and social bonding as major barriers to
      participating in learning discussion. DISCUSSION: Lack of time and peer response
      were given as the main reasons for low participation in social activity and
      learning discussions. Time and social bonding were major barriers to learning
      discussion. Course usefulness and participants' desire, commitment, and time
      management skills helped overcome barriers. Facilitators needed training in
      online systems and facilitation skills. Longer course duration and realistic
      pacing would probably foster more social interaction and greater course
      participation.

PMID- 18712802
TI  - Development of a mentorship strategy: a knowledge translation case study.
AB  - INTRODUCTION: There are many theories and frameworks for achieving knowledge
      translation, and the assortment can be confusing to those responsible for
      planning, evaluation, or policymaking in knowledge translation. A conceptual
      framework developed by Graham and colleagues provides an approach that builds on
      the commonalities found in an assessment of planned-action theories. This article
      describes the application of this knowledge to action framework to a mentorship
      initiative in academic medicine. Mentorship influences career success but is
      threatened in academia by increased clinical, research, and administrative
      demands. METHODS: A case study review was undertaken of the role of mentors, the
      experiences of mentors and mentees, and mentorship initiatives in developing and
      retaining clinician scientists at two universities in Alberta, Canada. This
      project involved relevant stakeholders including researchers, university
      administrators, and research funders. RESULTS: The knowledge to action framework
      was used to develop a strategy for mentorship for clinician researchers. The
      framework highlights the need to identify and engage stakeholders in the process
      of knowledge implementation. A series of initiatives were selected and tailored
      to barriers and facilitators to implementation of the mentorship initiative;
      strategies for evaluating the knowledge use and its impact on outcomes were
      developed. DISCUSSION: The knowledge to action framework can be used to develop a
      mentorship initiative for clinician researchers. Future work to evaluate the
      impact of this intervention on recruitment and retention is planned.

PMID- 18712803
TI  - A patient's feelings.

PMID- 18712804
TI  - Team- and case-based learning to activate participants and enhance knowledge: an
      evaluation of seminars in Germany.
AB  - INTRODUCTION: There is a strong need for high-quality continuing medical
      education (CME) in Germany. To maintain a medical license, physicians are
      required to participate in regular training. Although evidence suggests that
      compared to lectures interactive methods can impart sustainable knowledge and a
      high degree of satisfaction, few interactive CME courses are offered. METHODS: We
      designed an interactive, team-based CME concept and launched it in a series of
      seminars on internal medicine. The group work was designed using team-based
      learning. Pre- and postcourse knowledge tests with an electronic voting system
      and paper questionnaires (Likert scale 1-6) were used to evaluate knowledge,
      motivation, and expectations of the participants (n = 159). RESULTS: Participants
      rated the interactivity and team-based discussion (mean: 4.57, SD: 1.41) of the
      CME seminars as highly important reasons to participate and stated that the CME
      course was very instructional (mean: 5.16, SD: 0.84) and the case discussions
      enhanced their learning (mean: 5.46, SD: 0.75). The majority of participants
      stated that their expectations were met. The participants enhanced their outcome
      from a mean of 47.2% right answers prior to the course to 70.3% in the postcourse
      test ( p < 0.001). DISCUSSION: An interactive, case-based design of a CME course
      following the team-based learning concept leads to a significant gain in the
      participants' knowledge with an identified preknowledge level. Participants'
      expectations seemed fulfilled by a CME course design, which combines small group
      discussions in the lecture hall with didactic lectures and intensive discussion.

PMID- 18712805
TI  - Neonicotinoids-from zero to hero in insecticide chemistry.
AB  - In recent years, neonicotinoids have been the fastest-growing class of
      insecticides in modern crop protection, with widespread use against a broad
      spectrum of sucking and certain chewing pests. As potent agonists, they act
      selectively on insect nicotinic acetylcholine receptors, their molecular target
      site. The discovery of neonicotinoids can be considered as a milestone in
      insecticide research and facilitates greatly the understanding of the functional
      properties of insect nicotinic acetylcholine receptors. Because of the relatively
      low risk for non-target organisms and environment, the high target specificity of
      neonicotinoid insecticides and their versatility in application methods, this
      important class has to be maintained globally for integrated pest management
      strategies and insect resistance management programmes. This review
      comprehensively describes particularly the origin, structure and bonding as well
      as associated properties of neonicotinoid insecticides.

PMID- 18712806
TI  - Clusters of sirenomelia in South America.
AB  - BACKGROUND: One hospital in the city of Cali, Colombia, of the ECLAMC (Latin
      American Collaborative Study of Congenital Malformations) network, reported the
      unusual occurrence of four cases of sirenomelia within a 55-day period. METHODS:
      An ECLAMC routine for cluster evaluation (RUMOR) was followed that included:
      calculations of observed/expected ratios, site visits, comparison with
      comprehensively collected local, South American, and worldwide data, cluster
      analysis, and search for risk factors. RESULTS: All four Cali sirenomelia cases
      were born to mothers living in a 2 km(2) area, in neighboring communes, within
      the municipality of Cali. Considering the total births of the city of Cali as the
      denominator, and based on ECLAMC baseline birth prevalence rates (per 100,000)
      for sirenomelia (2.25, 95% CI: 2.66, 3.80), the cluster for this congenital
      abnormality was unlikely to have occurred by chance (observed/expected ratio =
      5.77; 95% CI: 1.57-14.78; p = .002). No consistent common factor was identified,
      but vicinity to an open landfill as the cause could not be rejected. Another
      ECLAMC hospital in San Justo, Buenos Aires, Argentina, reported three further
      cases but these did not seem to constitute a nonrandom cluster. CONCLUSIONS: The
      methodology used to evaluate the two possible clusters of sirenomelia determined
      that the Cali sirenomelia cluster was unlikely to have occurred by chance whereas
      the sirenomelia cluster from San Justo seemed to be random.

PMID- 18712807
TI  - A tribute to Lewis B. Holmes: mentor and scholar.

PMID- 18712808
TI  - Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene:
      effect of a dominant-negative GCM2 mutant associated with autosomal dominant
      hypoparathyroidism.
AB  - Glial cells missing-2 (GCM2) is a transcription factor expressed in the
      parathyroid hormone (PTH)-secreting cells of the parathyroid gland and is
      essential for their development. Thus far, downstream targets of GCM2 have not
      been identified. Here, we show that both promoters (P1 and P2) of the calcium
      sensing receptor (CASR) gene, a differentiation marker for the parathyroid gland,
      are transactivated by wild-type GCM2. GCM response elements within CASR P1 (-451
      to -441; relative to the transcription start site at +1) and CASR P2 (-166 to 
      156) were identified by mutated promoter-reporter studies as well as
      oligonucleotide precipitation assays. Primary hypoparathyroidism is a
      heterogeneous group of conditions characterized by hypocalcemia and
      hyperphosphatemia due to deficient PTH secretion. A few cases of familial
      isolated hypoparathyroidism with autosomal recessive inheritance have been
      identified that are caused by homozygous inactivating mutations in the GCM2 gene.
      We describe the GCM2 mutations in two families with hypoparathyroidism, one
      inherited in an autosomal recessive fashion and the other in an autosomal
      dominant manner. In transfection studies using a promoter-reporter construct
      having synthetic multimerized GCM elements in the promoter, the dominantly
      inherited mutant GCM2 exerted a dominant-negative effect on wild-type GCM2
      activity, whereas recessively inherited mutants did not. In addition, we show
      that the transactivation of the CASR promoter-reporter constructs by wild-type
      GCM2 is completely abolished in the presence of the dominant-negative mutant
      GCM2.

PMID- 18712809
TI  - Seroprevalence of human T-lymphotropic virus type 1 and 2 in Korean blood donors.
AB  - The seroprevalence rate of human T-lymphotropic virus (HTLV) among the Korean
      blood donor population was studied to determine whether screening for HTLV should
      be implemented. A total of 15,173 serum samples collected from June to July 2006
      at five Blood Centers which are located closely to Japan geographically, where
      the prevalence of HTLV is known to be high, were tested. Serological screening
      was done by a chemiluminescence method. Samples reactive repeatedly on
      serological screening were confirmed further by Western blot, line immunoassay,
      nested polymerase chain reaction and sequencing of proviral DNA. Six samples
      tested reactive with the serological assay showing a reactive rate of 0.004%.
      Among the six samples, one sample was confirmed as HTLV-1 positive, giving a
      confirmed reactive rate of 0.007%. Based on the results of this study, an
      extended study will be conducted to evaluate whether introduction of HTLV
      screening is necessary in Korea.

PMID- 18712810
TI  - Evidence of intrafamilial transmission of rotavirus in a birth cohort in South
      India.
AB  - Transmission of rotavirus infection was studied in a birth cohort of children
      based in an urban slum in Vellore and their familial contacts. Contemporaneous
      samples from index patients and their familial contacts were collected for
      analysis in three different settings. Firstly, samples were collected from
      familial contacts during a period of rotavirus infection in children from the
      cohort. Secondly, on occasions when a family member had rotavirus diarrhea,
      samples from the cohort child were taken for analysis. Lastly, asymptomatic
      surveillance samples collected at predetermined time points from both the cohort
      child and familial contacts were analyzed. From 560 samples collected from family
      members during symptomatic and asymptomatic rotavirus infections in these
      children, three rotavirus transmissions were identified, accounting for a
      secondary attack rate of 0.54%. In four instances of rotavirus diarrhea in a
      family member, one infection was transmitted to the cohort child. Nucleotide
      sequence and phylogenetic analysis demonstrated a high degree of similarity in
      all these pairs ranging between 99% and 100% at both the nucleotide and the
      deduced amino acid levels, highly suggestive of person-to-person transmission of
      rotavirus infection. There was complete concordance of rotavirus genotyping
      between these pairs. No transmission events were noted from 14 asymptomatic
      rotavirus infections identified during routine surveillance of family members.
      This study is the first to use phylogenetic analysis to study the intrafamilial
      spread of rotavirus infection.

PMID- 18712811
TI  - Development of nanofiber-covered stents using electrospinning: in vitro and acute
      phase in vivo experiments.
AB  - There are some technical difficulties in treating for a broad necked aneurysm and
      a higher incidence of recurrence. Because of these drawbacks, more innovative
      techniques for superior endovascular reconstructive treatment are required. We
      developed a novel covered stent employing electrospinning to deposit fine
      polyurethane (PU) fibers onto stents. An in vitro water leak test was designed
      and applied prior to animal testing to estimate the performance of covered stents
      and to determine the appropriate amount of PU fibers on a stent. Two tenths of a
      milligram of PU fibers proved to be sufficient to prevent water leakage. Then,
      the efficacy of the covered stents to that of bare stents was compared using 10
      rabbits in which model aneurysms had been formed at the right common carotid
      artery by the elastase method. Angiographic evaluation on day 1 posttreatment
      (acute phase) revealed complete occlusion of the aneurysms and the patency of the
      parent arteries in animals treated with covered stents. At 10 days poststenting
      (subacute phase), the aneurysm neck was completely covered with neointimal layer
      as shown by scanning electron microscopic examination. The PU-covered stent holds
      promise as a device for treating cerebral aneurysms.

PMID- 18712812
TI  - Inkjet printing of bioadhesives.
AB  - Over the past century, synthetic adhesives have largely displaced their natural
      counterparts in medical applications. However, rising concerns over the
      environmental and toxicological effects of the solvents, monomers, and additives
      used in synthetic adhesives have recently led the scientific community to seek
      natural substitutes. Marine mussel adhesive protein is a formaldehyde-free
      natural adhesive that demonstrates excellent adhesion to several classes of
      materials, including glasses, metals, metal oxides, and polymers. In this study,
      we have demonstrated computer aided design (CAD) patterning of various biological
      adhesives using piezoelectric inkjet technology. A MEMS-based piezoelectric
      actuator was used to control the flow of the mussel adhesive protein solution
      through the ink jet nozzles. Fourier transform infrared spectroscopy (FTIR),
      microscopy, and adhesion studies were performed to examine the chemical,
      structural, and functional properties of these patterns, respectively. FTIR
      revealed the piezoelectric inkjet technology technique to be nondestructive.
      Atomic force microscopy was used to determine the extent of chelation caused by
      Fe(III). The adhesive strength in these materials was correlated with the extent
      of chelation by Fe(III). Piezoelectric inkjet printing of naturally-derived
      biological adhesives may overcome several problems associated with conventional
      tissue bonding materials. This technique may significantly improve wound repair
      in next generation eye repair, fracture fixation, wound closure, and drug
      delivery devices.

PMID- 18712813
TI  - In vitro cytotoxicity of maxillofacial silicone elastomers: effect of accelerated
      aging.
AB  - The purpose of this in vitro study was to evaluate the cytotoxicity of three
      maxillofacial silicone elastomers at 24, 48, and 72 h on L-929 cells and to
      determine the effect of accelerated aging on the cytotoxicity of these silicone
      elastomers. Disc-shaped test samples of maxillofacial silicone elastomers
      (Cosmesil, Episil, Multisil) were fabricated according to manufacturers'
      instructions under aseptic conditions. Samples were then divided into three
      groups: (1) not aged; (2) aged for 150 h with an accelerated weathering tester;
      and (3) aged for 300 h. Then the samples were placed in Dulbecco's Modified Eagle
      Medium/Ham's F12 (DMEM/F12) for 24, 48, and 72 h. After the incubation periods,
      cytotoxicity of the extracts to cultured fibroblasts (L-929) was measured by MTT
      assay. The degree of cytotoxicity of each sample was determined according to the
      reference value represented by the cells with a control (culture without sample).
      Statistical significance was determined by repeated measurement ANOVA (p < 0.01)
      followed by Duncan's test (p < 0.05). All test materials in each group
      demonstrated high survival rates in MTT assay (Episil; 93.84%, Multisil; 88.30%,
      Cosmesil; 87.50%, respectively); however, in all groups, Episil material
      demonstrated significantly higher cell survival rate after each of the
      experimental incubation periods (p < 0.05). Accelerated aging for 150 and 300 h
      had no significant effect on the biocompatibility of maxillofacial silicone
      elastomers tested (p > 0.05).

PMID- 18712814
TI  - Immune suppression leading to hepatitis C virus re-emergence after sustained
      virological response.
AB  - Sustained virological response SVR is defined as undetectable HCV RNA in plasma 6
      months after therapy has been discontinued. Relapse or re-emergence of viremia
      after SVR is rare. We report two patients that relapsed when immune suppressive
      therapy was given within a few weeks of achieving SVR. Patient 1 received
      prednisone for bronchitis and patient 2 relapsed soon after immune suppression
      was started post renal transplantation. These data suggest that the early phase
      of SVR might be associated with incomplete protective immunity. They suggest that
      sterilizing immunity with complete elimination of virus is unlikely. The cases
      also caution against the use of immune suppressive therapy in the immediate
      aftermath of SVR.

PMID- 18712815
TI  - Brief report: acute viral hepatitis and poor maternal and perinatal outcomes in
      pregnant Sudanese women.
AB  - Sixteen pregnant women presented at the three main hospitals in Khartoum
      province, Sudan during the period of March-September 2007 with features of acute
      viral hepatitis. Their mean (SD) gestational age was 28.0(6.7) weeks. The
      etiology of acute viral hepatitis was hepatitis B virus in five women (31.3%),
      hepatitis C virus in one woman (6.3%), hepatitis E virus in eight women (50%),
      and hepatitis non-A-to-E virus in two women (12.5%). There were four (25%)
      maternal deaths and three (18.7%) intrauterine fetal deaths. Three of these
      maternal deaths were due to hepatitis E virus and the fourth was due to hepatitis
      B virus.

PMID- 18712816
TI  - Genetic diversity of norovirus, sapovirus, and astrovirus isolated from children
      hospitalized with acute gastroenteritis in Chiang Mai, Thailand.
AB  - Norovirus (NV), sapovirus (SV), and human astrovirus (HAstV) are important causes
      of acute gastroenteritis in infants and young children. This study investigated
      the prevalence of NV, SV, and HAstV infections in children hospitalized with
      acute gastroenteritis in Chiang Mai, Thailand from May 2000 to March 2002. Fecal
      specimens were tested for NV, SV, and HAstV by reverse transcription polymerase
      chain reaction (RT-PCR) using degenerate specific primers. These viruses were
      characterized further by sequence and phylogenetic analyses of the partial capsid
      gene. From 296 fecal specimens tested, 13.5% (40 of 296) were positive for NV,
      SV, and HAstV. Of these, NV most predominant, with a prevalence of 60% (24 of
      40), of which 17.5% were NVGI and 42.5% were NVGII. Of note, one specimen was
      positive for both NVGI and SV. SV was detected in 25%, while HAstV was detected
      in 17.5%. Analysis of nucleotide and amino acid sequences revealed that NVGI
      strains comprised GI/3, GI/4, GI/6, GI/7, and GI/13 genotypes. Among NVGII
      strains, approximately half of them belonged to genotype GII/4 (Lordsdale virus
      cluster), followed by GII/3, GII/10, GII/1, GII/6, GII/8, and GII/15. Analysis of
      SV sequences revealed that SVGI (Manchester virus) was more common than SVGII
      (London virus). The SV genotypes detected in this study belonged to SVGI/1,
      SVGI/4, SVGI/5, SVGII/1, and SVGII/2, whereas the HAstV belonged to genotypes
      HAstV-1, HAstV-2, HAstV-3, and HAstV-5. The findings suggest that NV, SV, and
      HAstV are important enteric viruses cocirculating among hospitalized children in
      Chiang Mai, Thailand.

PMID- 18712817
TI  - Multiple outbreaks of acute hemorrhagic conjunctivitis due to a variant of
      coxsackievirus A24: Guangdong, China, 2007.
AB  - Acute hemorrhagic conjunctivitis (AHC) is usually caused by enterovirus 70,
      coxsackievirus A24(CA24v) and adenoviruses. Several outbreaks of AHC caused by a
      CA24v have occurred since it was imported into China in 1971. Multiple outbreaks
      of AHC reappeared in 10 cities of Guangdong during June to November in 2007. The
      epidemic began in the June, and spread extensively, with a peak in the September.
      A total of 31,659 cases were reported to center for disease control and
      prevention of Guangdong, it was estimated that the number of actual AHC was >200
      thousands. Forty conjunctival swab specimens were collected from the cases
      diagnosed clinically with AHC. (RT)-PCR testing on these conjunctival specimens
      revealed the presence of an enterovirus, and this was confirmed by 16 isolates.
      We demonstrated the most likely etiological agent for the multiple outbreaks was
      a variant of coxsackievirus A24 by molecular typing using a partial VP1 sequence.
      Sequence comparison and phylogenetic analyses of the VP1 and 3Cpro gene regions
      were performed by Neighbor-joining method, the strains from different outbreaks
      and different geographical areas within Guangdong had no sequence divergence in
      2007. The representative isolates from mainland of China including Hangzhou,
      Ningbo, Beijing, Yunnan, Liaoning, and Henan were analyzed in this study.
      Phylogenetic analysis revealed theses isolates were located in different
      clusters, a close phylogenetic and chronological relationship with Singaporean,
      South Korean and Thailand isolates had been observed. This confirms CA24v
      circulated in China's mainland has not evolved independently, but co-evolved with
      the isolates of Southeast Asia.

PMID- 18712818
TI  - Detection of cytomegalovirus, parvovirus B19 and herpes simplex viruses in cases
      of intrauterine fetal death: association with pathological findings.
AB  - There are previous indications that transplacental transmission of
      cytomegalovirus (CMV), parvovirus B19 (PB19) and herpes simplex virus types 1 and
      2 (HSV-1/2) cause fetal infections, which may lead to fetal death. In a
      prospective case-control study we examined the incidence of these viruses in
      intrauterine fetal death and their association with fetal and placenta
      pathological findings. Molecular assays were performed on placenta tissue
      extracts of 62 fetal deaths and 35 controls for the detection of CMV, PB19 and
      HSV-1/2 genomes. Formalin-fixed, paraffin-embedded liver, spleen and placenta
      tissues of fetal death cases were evaluated histologically. Thirty-four percent
      of placental specimens taken from intrauterine fetal deaths were positive for any
      of the three viruses (16%, 13%, and 5% positive for CMV, PB19, and HSV-1/2,
      respectively), whereas only 6% of those taken from full term newborns were
      positive (P = 0.0017). No dual infection was observed. This difference was also
      observed when fetal deaths with a gestational age <20 weeks or a gestational age
      >20 weeks were compared with the controls (P = 0.025 and P = 0.0012,
      respectively). Intrauterine death and the control groups differed in the
      detection rate of CMV DNA (16% and 3%, respectively; P = 0.047), which was more
      pronounced in a gestational age >20 weeks (P = 0.03). Examination of the
      pathological findings among the PCR-positive and PCR-negative fetal deaths
      revealed that hydrops fetalis and chronic villitis were more common among the
      former group (P = 0.0003 and P = 0.0005, respectively). In conclusion, an
      association was detected between viral infection and fetal death, which was more
      pronounced in the advanced gestational age. Fetal hydrops and chronic villitis
      were evidently associated with viral DNA detection in cases of intrauterine
      death.

PMID- 18712819
TI  - Molecular characterization of enteric viral agents from children in northern
      region of Ghana.
AB  - Viral gastrointestinal infections are among the most important causes of
      childhood morbidity and mortality, especially in non-industrialized countries.
      The objective of this study was the molecular characterization of rotaviruses,
      noroviruses, adenoviruses, astroviruses, and enteroviruses obtained from 367
      children in the Northern Region of Ghana. One hundred and forty-two rotavirus
      positive stool samples were examined. The most frequent type identified was
      G1P[8] occurring in 80% of the cases. Of 27 norovirus positive samples, 5
      isolates belonged to genogroup I and 22 to genogroup II. Adenoviruses were
      detected in 73 samples; 23.3% of these belonged to genogroup F, 31.5% to D, 17.8%
      to A, 15.1% to C, and 12.3% to B. Astrovirus typing of 12 positive samples
      displayed a distribution into four different genotypes: five sequences clustered
      with AstV-8, four with AstV-2, two with AstV-5, and one with AstV-6. Twenty-three
      different enterovirus types were identified in 45 positive samples,
      coxsackievirus A24 being the most frequent pathogen (18%). This first,
      comprehensive molecular characterization of enteric viruses in northern Ghana
      provides baseline data for the molecular epidemiology of these pathogens and
      immunisation strategies. The available rotavirus vaccines cover the predominant
      G1P[8] type and would reduce substantially disease burden in that area.

PMID- 18712820
TI  - Viruses in community-acquired pneumonia in children aged less than 3 years old:
      High rate of viral coinfection.
AB  - The occurrence of viral coinfections in childhood pneumonia has received little
      attention, probably because suitable detection methods have been lacking. Between
      November 2004 and October 2006, the presence of 14 respiratory viruses in
      children aged less than 3 years old with community-acquired pneumonia were
      investigated using molecular or immunochromatographic techniques and/or viral
      culture. A total of 315 children (338 episodes) were included, and
      hospitalization was required in 178 episodes. At least one virus was detected in
      66.9% of the episodes and simultaneous detection of two or more viruses was
      frequent (27% of the episodes with viral detection). The most frequently detected
      virus was respiratory syncytial virus (n = 67: 33 subgroup A, 33 subgroup B, 1
      not typed), followed by human bocavirus (n = 48), rhinovirus (n = 46), human
      metapneumovirus (n = 39: 13 genotype A2, 8 B1, 5 B2, 1 A1, 12 not genotyped) and
      parainfluenza viruses (n = 38: 1 type 1, 3 type 2, 22 type 3, 11 type 4 and 1 not
      typed). The 14 viruses investigated were found in viral coinfections, which were
      more frequent in children aged less than 12 months. Except for adenovirus, the
      incidence of which was low, the percentage of viral coinfection ranged between
      28.2% and 68.8%. Children with viral coinfection more frequently required
      hospital admission than those with single viral infection. It is concluded that
      viral coinfections are frequent in children aged less than 3 years old with
      community-acquired pneumonia and can be a poor prognostic factor.

PMID- 18712824
TI  - HIV-1 diversity among inmates of Italian prisons.
AB  - In Italy, the prevalence of non-B HIV-1 subtypes ranges reportedly from 5.4% to
      12.6%, yet there are no data on their circulation in prisons, where the
      prevalence of HIV infection is high. A retrospective study was conducted to
      evaluate the circulation of non-B subtypes and to characterize their determinants
      in five Italian prisons. To this end an aliquot of samples of blood was taken in
      the period 2001-2006 from all 262 HIV-positive inmates in whom antiretroviral
      treatment had failed. Complete HIV-1 PR and RT regions were sequenced for all
      samples and subjected to phylogenetic analysis; 250 (95.4%) sequences clustered
      with subtype B. The non-B subtype was found in 4% of Italian prison inmates and
      16.7% of non-Italian prison inmates; the overall percentage increased from 1.8%
      for inmates infected in 1982-1990 to 4.4% in 1991-1999 and 21.9% in 2000-2006.
      Factors significantly associated with non-B subtypes were an exposure to other
      than injecting drug use and a first positive HIV test in 2000-2006. Non-B
      subtypes were distributed within five monophyletic clades. In all cases but one,
      it was possible to correlate the history of HIV-exposure to the origin of the
      clade, with high bootstrap values. In conclusion, although the sample may not be
      representative of the prison inmate population in Italy, the data suggest
      strongly that the circulation of non-B subtypes has apparently increased. Non-B
      subtypes were found to have been associated with heterosexual contact and time of
      the first HIV-positive test. Knowledge of the different subtypes circulating in
      prisons may be useful for tracking the epidemiology of HIV infection and for
      choosing antiretroviral therapy.

PMID- 18712825
TI  - Identification of hepatitis C virus genotype 6 in Korean patients by analysis of
      5' untranslated region using a matrix assisted laser desorption/ionization time
      of flight-based assay, restriction fragment mass polymorphism.
AB  - Previous surveys of the prevalence of hepatitis C virus (HCV) in Korea have
      identified types 1 and 2, but little has been said of other genotypes and viral
      subtypes. In this study, HCV genotypes in Korea were investigated using
      Restriction Fragment Mass Polymorphism (RFMP) assay, a sensitive and specific
      method for genotyping based on MALDI-TOF mass spectrometry. A total of 1,043
      independent serum samples from HCV-infected patients were analyzed. Of interest,
      15 subjects (1.4%) were determined to contain HCV genotype 6 and 46 subjects
      (4.4%) contained mixed genotypes with the most prevalent genotypes being HCV 1b
      and 2a/c (45.0% and 35.4%, respectively). The 15 subjects with HCV genotype 6
      comprised eight cases of subtype 6c, including one case of mixed infection with
      1b, three cases of HCV 6a, and six cases of unassigned subtypes. Sequencing
      corroborated the identity of genotype 6 from 13 subjects, while the line probe
      assay (LiPA) mis-identified them as genotype 1b. The majority (7/9) of the
      genotype 6 patients enrolled for interferon/ribavirin therapy, achieved a
      sustained virologic response. The ability of the RFMP assay to differentiate
      various HCV genotypes should enable better analysis of the relationship between
      HCV genotype and disease prognosis.

PMID- 18712826
TI  - Charged single alpha-helix: a versatile protein structural motif.
AB  - A few highly charged natural peptide sequences were recently suggested to form
      stable alpha-helical structures in water. In this article we show that these
      sequences represent a novel structural motif called "charged single alpha-helix"
      (CSAH). To obtain reliable candidate CSAH motifs, we developed two conceptually
      different computational methods capable of scanning large databases: SCAN4CSAH is
      based on sequence features characteristic for salt bridge stabilized single alpha
      helices, whereas FT_CHARGE applies Fourier transformation to charges along
      sequences. Using the consensus of the two approaches, a remarkable number of
      proteins were found to contain putative CSAH domains. Recombinant fragments (50
      60 residues) corresponding to selected hits obtained by both methods (myosin 6,
      Golgi resident protein GCP60, and M4K4 protein kinase) were produced and shown by
      circular dichroism spectroscopy to adopt largely alpha-helical structure in
      water. CSAH segments differ substantially both from coiled-coil and intrinsically
      disordered proteins, despite the fact that current prediction methods recognize
      them as either or both. Analysis of the proteins containing CSAH motif revealed
      possible functional roles of the corresponding segments. The suggested main
      functional features include the formation of relatively rigid spacer/connector
      segments between functional domains as in caldesmon, extension of the lever arm
      in myosin motors and mediation of transient interactions by promoting
      dimerization in a range of proteins.

PMID- 18712823
TI  - Antiretroviral genotypic resistance in plasma RNA and whole blood DNA in HIV-1
      infected patients failing HAART.
AB  - The extent to which HIV-1 proviral DNA mutations cause clinically relevant
      antiretroviral resistance is still controversial. Paired plasma HIV-1 RNA and
      whole blood DNA were compared in patients failing HAART to investigate if the
      additional knowledge of archived mutations could improve the selection of
      potentially active drugs. Seventy-three HIV-1-infected patients with first/second
      HAART failure were studied before starting a new regimen based on RNA genotyping.
      Follow-up data after a 12-week therapy were available. DNA genotyping was
      retrospectively performed on stored whole blood samples and mutational profiles
      were compared to those from RNA. The mean number of IAS pol mutations was
      significantly higher in RNA (4.45 +/- 2.76) than in DNA (2.88 +/- 2.47) (P <
      0.001). DNA genotyping provided a 6% increase in detection of resistance
      associated mutations. Among 64/73 patients showing discordant DNA/RNA profiles,
      54 (84%) also differed for predicted active drugs. 16/73 (22%) patients had >or=1
      mutation revealed by DNA genotyping alone, probably affecting therapy success in
      2/16. However, neither RNA/DNA discordance nor detection of isolated DNA
      mutations were statistically associated with outcome. In conclusion, plasma RNA
      remains the elective choice for HIV genotyping in patients with therapy failure,
      even if the detection of proviral resistance-associated mutations, not
      simultaneously found in RNA, is a frequent event. Therefore, in some cases DNA
      plus RNA genotyping might assist in choosing more accurately subsequent
      antiretroviral regimens.

PMID- 18712828
TI  - Crystal structure of engineered beta-glucosidase from a soil metagenome.

PMID- 18712827
TI  - Iterative cluster-NMA: A tool for generating conformational transitions in
      proteins.
AB  - Computational models provide insight into the structure-function relationship in
      proteins. These approaches, especially those based on normal mode analysis, can
      identify the accessible motion space around a given equilibrium structure. The
      large magnitude, collective motions identified by these methods are often well
      aligned with the general direction of the expected conformational transitions.
      However, these motions cannot realistically be extrapolated beyond the local
      neighborhood of the starting conformation. In this article, the iterative cluster
      NMA (icNMA) method is presented for traversing the energy landscape from a
      starting conformation to a desired goal conformation. This is accomplished by
      allowing the evolving geometry of the intermediate structures to define the local
      accessible motion space, and thus produce an appropriate displacement. Following
      the derivation of the icNMA method, a set of sample simulations are performed to
      probe the robustness of the model. A detailed analysis of beta1,4
      galactosyltransferase-T1 is also given, to highlight many of the capabilities of
      icNMA. Remarkably, during the transition, a helix is seen to be extended by an
      additional turn, emphasizing a new unknown role for secondary structures to
      absorb slack during transitions. The transition pathway for adenylate kinase,
      which has been frequently studied in the literature, is also discussed.

PMID- 18712829
TI  - Crystal structure of a family GT4 glycosyltransferase from Bacillus anthracis ORF
      BA1558.

PMID- 18712830
TI  - Prevalence of HBV genotypes in Central and Eastern Europe.
AB  - The importance of hepatitis B virus (HBV) genotypes for disease progression and
      response to interferon-alpha-based treatment is well established. While almost
      all patients in the Mediterranean area are infected with HBV genotype D, HBV
      genotype A is dominant in Northern Europe. However, the distribution of HBV
      genotypes is unknown for several Central and Eastern European countries. Data are
      described of 1313 HBsAg-positive patients recruited at 14 referral centers in
      eight countries. There were only very few cases of HBV genotype B, C, E, F, and H
      infection while HBV genotypes A and D were found in 42% and 48% of patients,
      respectively. Eight percent of patients had positive bands for more than one
      genotype using the hybridization assay. The frequency of genotype A was higher in
      Poland (77%) and the Czech Republic (67%) as compared to Hungary (47%), Lithuania
      (41%), Croatia (8%), and Germany (32%). In contrast, HBV genotype D was most
      frequent in Croatian, Romanian, and Russian patients with 80%, 67%, and 93% of
      cases, respectively. In conclusion, HBV genotype A versus D showed significantly
      different distribution patterns in Central and Eastern Europe which deserves
      consideration for national guidelines and treatment decisions.

PMID- 18712831
TI  - Complete genome sequencing and phylogenetic analysis of HCV isolates from China
      reveals a new subtype, designated 6u.
AB  - Full length genome sequences were characterized for three novel hepatitis C virus
      (HCV) isolates (here named DH012, DH014, and DH028). The complete genomes were
      all isolated from injecting drug users (IDUs) who were co-infected with HIV-1 and
      lived in Dehong prefecture, Yunnan Province, China, which neighbors Myanmar. The
      three genomes are 9,443-9,470 nt in length and each contains a single open
      reading frame (ORF) of 9,069 nt long. Pairwise comparisons indicated nucleotide
      similarities of 97.9-98.6% among the three isolates, and similarities of 72.4
      75.0% between the three isolates and 20 reference strains (representing HCV
      subtypes 6a-6q and 6t plus two unassigned genotype 6 isolates km41 and gz52557).
      Phylogenetic analyses demostrated that the three isolates formed a tight and well
      supported monophyletic cluster in the genotype 6 clade. No evidence of viral
      recombination was found using similarity plots and bootscanning analyses. Based
      on the current HCV classification criteria, we have assigned the three isolates
      to a new subtype, 6u. Although another "6u" isolate D83 has been reported very
      recently, it is subtypically distinct from the three isolates we described here.
      Because its designation does not meet the criteria described in the updated HCV
      nomenclature proposal, this "6u" isolate should be reclassified.

PMID- 18712832
TI  - Prevalence and genotype identification of human JC virus in colon cancer in
      Taiwan.
AB  - Although JC virus (JCV), a human polyomavirus, has been detected in colon
      cancers, the association between JCV and colon cancer remains controversial. In
      Taiwan, the prevalence of JCV infection in colon cancer patients has not been
      reported. Thus, the purpose of this study was to investigate JCV infection in
      colon cancers in Taiwan. Formalin-fixed, paraffin-embedded tissues from 22 colon
      cancer patients were examined in this study. Nested PCR was performed to detect
      viral genomic DNA. The product of the nested PCR flanking the JCV regulatory
      region was sequenced further. Viral large tumor protein, LT, and late capsid
      protein, VP1, were examined by immunohistochemistry (IHC). Nested PCR revealed
      JCV genomic DNA in 86.4% (19/22) of the colon cancer tissue samples. Both
      rearranged and archetypal genotypes of JCV were identified. Expression of JCV LT
      was positive in 63.6% (14/22) of the examined colon cancer tissue samples but not
      in any adjacent normal region. Expression of viral capsid protein VP1 was not
      detected in any of the tissues examined. The current study demonstrates that JCV
      genomic DNA was present in the examined colon cancer tissues. The genotypes of
      JCV in colon cancer tissues were also identified. Expression of viral early
      protein but not structural capsid protein was detected in the examined colon
      cancer tissues. Furthermore, a high prevalence of JCV infection in colon cancer
      tissues in Taiwan was also demonstrated.

PMID- 18712833
TI  - Case report: persistent cytomegalovirus (CMV) infection after haploidentical
      hematopoietic stem cell transplantation using in vivo alemtuzumab: emergence of
      resistant CMV due to mutations in the UL97 and UL54 genes.
AB  - Addition of in vivo alemtuzumab to the conditioning regimen enabled 2- or 3-locus
      mismatched hematopoietic stem cell transplantation with an acceptable incidence
      of graft-versus-host-disease. However, the procedure was associated with a high
      incidence of cytomegalovirus (CMV) reactivation. Although preemptive therapy with
      ganciclovir prevented successfully severe CMV diseases and CMV-related mortality,
      a patient developed persistent positive CMV antigenemia for more than 1 year
      after transplantation and CMV disease, despite the use of ganciclovir and
      foscarnet. The in vitro susceptibility assay showed that the clinical isolate was
      resistant to foscarnet, moderately resistant to ganciclovir, but sensitive to
      cidofovir. Therefore, cidofovir was administered. CMV antigenemia became negative
      within 2 weeks and never developed again. Nucleotide sequence of the UL54 and
      UL97 of the clinical isolate showed 4 amino acid substitutions (V11L, Q578H,
      S655L, and G874R) in UL54 and 2 mutations (A140V and A594V) in UL97 compared with
      the Towne and AD169 strains. Ganciclovir resistance was suspected to be caused by
      both A594V of UL97 and Q578H of UL54, whereas foscarnet resistance was due mainly
      to Q578H of UL54. In conclusion, the in vitro susceptibility assay as well as
      nucleotide sequence of clinical isolate is important to choose appropriate
      antiviral agents for patients who have persistent CMV reactivation after stem
      cell transplantation.

PMID- 18712834
TI  - Case report: human herpesvirus 6 reactivation associated with colitis in a lung
      transplant recipient.
AB  - Whereas human herpesvirus 6 (HHV-6) reactivation is frequent in solid organ
      transplant recipients, symptomatic disease is rare. A case of colitis associated
      with HHV-6B reactivation was observed in a lung transplant recipient. This case
      report suggests that symptomatic HHV-6 infection may occur in the absence of
      detectable viremia.

PMID- 18712835
TI  - The analysis of the entire HLA, partial non-HLA and HPV for Chinese women with
      cervical cancer.
AB  - Human leukocyte antigen (HLA) alleles have been associated with an increased or
      decreased risk of developing cervical cancer through infection with oncogenic
      forms of the human papillomavirus (HPV). The aim of this study was to analyze the
      interactions between HPV and HLA, particularly of the entire HLA and partial non
      HLA regions, in invasive cervical cancers. The results showed the distribution of
      HPV genotypes among patients with cervical cancer in this group: the overall
      prevalence of HPV DNA was 91.3% (274/300). A total of 16 HPV genotypes, HPV16,
      18, 58, 33, 81, 31, 68, 39, 67, 6, 11, 26, 52, 62, 66, and 70, were detected in
      patients with cervical cancer. Among the cervical cancer specimens, 68.7% were
      positive for HPV16. Genotyping was performed with 112 microsatellite markers
      spanning the entire HLA region and partial region of chromosome 6q15-16.3.
      D6S2766 and D6S2764, which are located near to the region containing the HLA-DPB
      genes, were negatively related with cervical cancer (OR for the D6S2766-195
      allele carriers = 0.50), and positively related with cervical cancer (OR for the
      D6S2764-209 allele carriers = 2.44), respectively. Significant association was
      found for D6S1043 (allele 132) with HPV16-positive cervical cancer (OR = 4.52).
      There was an increased risk for carriers of alleles 112 and 132 at the D6S1043
      locus, in particular for homozygotes. The present findings indicate that the
      antigenic presentation of HPV-derived peptides and non-HLA regions may be
      involved in the pathogenesis of HPV-associated cervical cancer.

PMID- 18712836
TI  - Prevalence and genotype distribution of multiple human papillomavirus infection
      in the uterine cervix: a 7.5-year longitudinal study in a routine cytology-based
      screening population in West Germany.
AB  - The availability of vaccines against certain HPV types and the development of
      broad spectrum genotyping methods have increased interest in co-infections with
      different HPV types. In the present study, the prevalence and type-specific
      composition of multiple HPV infections were investigated in a routine cervical
      screening population in West Germany both at a cross-sectional level and
      longitudinally. Four hundred eighty-nine out of 8,090 women were diagnosed with
      multiple HPV infections once or repeatedly. During the 7.5-year study period, the
      cumulative prevalence of HPV co-infections was 15.3% in contrast to the cross
      sectional prevalence of 3.8% at single visits. The overall cumulative prevalence
      within the cohort of all women screened was 6.9%. Using consensus PCR with
      sequencing and type-specific PCRs, two to three HPV types were detected
      simultaneously, whereas broad spectrum methods detected up to seven different
      genotypes in one sample. Nevertheless, the most common pattern of co-infection
      occurred with two to three HPV types irrespective of the age of the patient,
      cytology and histology of the lesions and the method used. The most common
      genotypes detected were HPV 16, 31, 53, 51, 52, and 66, and the most common
      pattern of co-infection was double infection with HPV 16 and 31. These results
      show that rates and patterns of multiple HPV infections are largely dependent on
      the methodology used and the time interval between tests. Given the significance
      of HPV vaccination and its expected influence on immunized populations, it is
      essential to gain additional insights into the natural course and pathogenic
      effect of multiple HPV infection longitudinally.

PMID- 18712837
TI  - Acute respiratory infection and influenza-like illness viral etiologies in
      Brazilian adults.
AB  - Influenza-like illness (ILI) definitions have been used worldwide for influenza
      surveillance. These different case definitions can vary with regard to
      sensitivity and predictive values for laboratory confirmed influenza. The
      literature has indicated the inclusion of other viruses may be the cause of these
      variable results. The objective of the study was to evaluate ILI national
      sentinel criteria and viral etiologies in adults diagnosed with acute respiratory
      infection (ARI) and/or ILI from 2001 to 2003 in Sao Paulo, Brazil. Clinical and
      laboratory evaluations were observed from 420 adults and collected on a daily
      basis from outpatient care units at University Hospital. The ILI definition
      included: fever plus at least one respiratory symptom (cough and/or sore throat)
      and one constitutional symptom (headache, malaise, myalgia, sweat or chills, or
      fatigue). DFA and RT-PCR for influenza, parainfluenza, respiratory syncytial
      virus, adenovirus, enterovirus, coronavirus, rhinovirus, and metapneumovirus were
      performed on nasal washes and 61.8% resulted positive. The respiratory viruses
      detected most often were influenza and rhinovirus. ILI was reported for 240/420
      patients (57.1%), with influenza and rhinovirus etiologies accounting for 30.9%
      and 19.6%, respectively. Rhinovirus peak activity was concurrent with the
      influenza season. These findings highlight the implications of other viruses in
      ILI etiology and suggest that during the influenza season, this clinical overlap
      must be considered in the diagnosis and clinical management of patients.

PMID- 18712838
TI  - Genotype-phenotype correlation in PEX5-deficient peroxisome biogenesis defective
      cell lines.
AB  - Proteins destined for the peroxisomal matrix are targeted by virtue of a
      peroxisomal targeting sequence type 1 (PTS1) or type 2 (PTS2). In humans,
      targeting of either class of proteins relies on a cytosolic receptor protein
      encoded by the PEX5 gene. Alternative splicing of PEX5 results in two protein
      variants, PEX5S and PEX5L. PEX5S is exclusively involved in PTS1 protein import,
      whereas PEX5L mediates the import of both PTS1 and PTS2 proteins. Genetic
      complementation testing with over 500 different fibroblast cell lines from
      patients diagnosed with a peroxisome biogenesis disorder (PBD) identified 11 cell
      lines with a defect in PEX5. The aim of this study was to characterize these cell
      lines at a biochemical and genetic level. To this end, the cultured fibroblasts
      were analyzed for very long chain fatty acid (VLCFA) concentrations, peroxisomal
      beta-and alpha-oxidation, dihydroxyacetone-phosphate acyltransferase (DHAPAT)
      activity, peroxisomal thiolase, and catalase immunofluorescence. Mutation
      analysis of the PEX5 gene revealed 11 different mutations, eight of which are
      novel. PTS1- and PTS2-protein import capacity was assessed by transfection of the
      cells with green fluorescent protein (GFP) tagged with either PTS1 or PTS2. Six
      cell lines showed a defect in both PTS1 and PTS2 protein import, whereas four
      cell lines only showed a defect in PTS1 protein import. The location of the
      different mutations within the PEX5 amino acid sequence correlates rather well
      with the peroxisomal protein import defect observed in the cell lines.

PMID- 18712840
TI  - Serum thrombospondin-1 is altered in patients with hemorrhagic fever with renal
      syndrome.
AB  - Hemorrhagic fever with renal syndrome (HFRS) is a severe acute viral disease with
      pathological changes of impaired capillary and small vessels and
      thrombocytopenia. In this study, serum thrombospondin (TSP)-1 concentration in
      patients with HFRS was determined to explore its possible role in the
      pathogenesis of HFRS. The concentration of TSP-1 was measured using a competitive
      enzyme-linked immunoabsorbent assay. Significantly decreased levels of serum TSP
      1 were observed in HFRS patients at febrile and hypotensive phases compared with
      those in the controls. The serum levels of TSP-1 in HFRS patients with more
      severe clinical types was reduced more profoundly than those in patients with
      milder clinical types at febrile and hypotensive phases, although the differences
      in TSP-1 were not significant. It was indicated that insufficient production or
      increased consumption of TSP-1, or both of these, may contribute to the
      impairment of capillary and small vessels and the development of hypotension at
      the early stage of HFRS, and the decreased degree may be associated with disease
      severity.

PMID- 18712839
TI  - Pathogenic role of natural killer T and natural killer cells in acetaminophen
      induced liver injury in mice is dependent on the presence of dimethyl sulfoxide.
AB  - Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve
      drugs and enzyme inhibitors with low solubility. Although DMSO is generally
      thought of as being relatively inert, it can induce biological effects that are
      often overlooked. An example that highlights this potential problem is found in a
      recent report demonstrating a pathogenic role for natural killer T (NKT) and
      natural killer (NK) cells in acetaminophen-induced liver injury (AILI) in C57Bl/6
      mice in which DMSO was used to facilitate acetaminophen (APAP) dissolution. We
      report that NKT and NK cells do not play a pathologic role in AILI in C57Bl/6
      mice in the absence of DMSO. Although AILI was significantly attenuated in mice
      depleted of NKT and NK cells prior to APAP treatment in the presence of DMSO, no
      such effect was observed when APAP was dissolved in saline. Because of this
      unexpected finding, the effects of DMSO on hepatic NKT and NK cells were
      subsequently investigated. When given alone, DMSO activated hepatic NKT and NK
      cells in vivo as evidenced by increased NKT cell numbers and higher intracellular
      levels of the cytotoxic effector molecules interferon-gamma (IFN-gamma) and
      granzyme B in both cell types. Similarly, when used as a solvent for APAP, DMSO
      again increased NKT cell numbers and induced IFN-gamma and granzyme B expression
      in both cell types. CONCLUSION: These data demonstrate a previously unappreciated
      effect of DMSO on hepatic NKT and NK cells, suggesting that DMSO should be used
      cautiously in experiments involving these cells.

PMID- 18712841
TI  - Longitudinal observation of parechovirus in stool samples from Norwegian infants.
AB  - Parechoviruses are assumed to be common infectious agents, but their
      epidemiologic and pathogenic properties are not well known. The aim of the
      present study was to assess the prevalence and molecular epidemiology of
      Parechovirus in Norwegian infants, as well as to investigate whether the presence
      of virus correlated with symptoms of infection. A group of 102 infants was
      longitudinally followed: 51 infants with a high genetic risk for type 1 diabetes
      (aged 3-35 months), and 51 children without this genotype (aged 3-12). Stool
      samples were obtained each month, and symptoms of infection were recorded
      regularly on questionnaires. Human parechovirus was detected in 11.3% of 1,941
      samples examined by real-time RT-PCR. There was a distinct seasonality, peaking
      from September to December. By 12 months of age, 43% of the infants had had at
      least one infection, while 86% of the infants had encountered the virus by the
      end of the second year. Based on the VP1 sequence, human parechovirus 1 was the
      most prevalent type (76%), followed by human parechovirus 3 (13%), human
      parechovirus 6 (9%), an unclassified human parechovirus (1%), and human
      parechovirus 2 (1%). Ljungan virus, a murine parechovirus, was examined with a
      separate real-time RT-PCR, but no virus was detected. There was no significant
      association between infections and the following symptoms: coughing, sneezing,
      fever, diarrhea or vomiting. In conclusion, human parechovirus infects frequently
      infants at an early age without causing disease.

PMID- 18712843
TI  - Nerve transfers in children with traumatic partial brachial plexus injuries.

PMID- 18712842
TI  - Biologic diversity of polyomavirus BK genomic sequences: Implications for
      molecular diagnostic laboratories.
AB  - Data on polyomavirus genomic diversity has greatly expanded in the past few
      years. The implications of viral DNA sequence variation on the performance of
      molecular diagnostic assays have not been systematically examined. 716 BK, 1626
      JC, and 73 SV40 virus sequences available in GenBank were aligned using Clustal
      X. Five different published BKV PCR assays currently in use at major medical
      centers were evaluated for primer and probe mismatches with available GenBank
      sequences. Coverage of naturally occurring BKV strains varied amongst different
      assay methods. Targeted viral sequences showed major mismatch with primer or
      probe sequence in up to 30.7% of known BKV strains. BKV subtypes IVa, IVb, and
      IVc were more prone to this problem, reflecting common use of Type I Dun sequence
      for assay design. Despite the known polymorphism of this gene, 484 VP-1 sequences
      with conserved areas potentially suitable for PCR assay design are available.
      Assay targets in the Large T-antigen and agnogene are less subject to genetic
      variation, but sequence information corresponding to the latter two genes is
      available only for 164 and 174 published strains, respectively. Cross reactivity
      of appropriately selected BKV primers with JCV and SV40 sequences available in
      current databases was not a significant problem.

PMID- 18712844
TI  - Salvage of amputated thumbs by temporary ectopic implantation.
AB  - PURPOSE: To determine the indications and benefits of ectopic implantation in the
      salvage of amputated thumb. BASIC PROCEDURES: Two cases of avulsed amputated
      thumbs were temporarily ectopically implanted onto the forearm and foot, with
      microvascular anastomoses. When the stump condition allowed, and the soft-tissue
      defects were repaired, the ectopic implanted thumbs were replanted to their
      anatomic positions. RESULTS: Both thumbs survived the temporary ectopic
      implantation and second-stage replantation. The length of the thumbs was
      maintained, and the thumbs regained their function in 16- and 10-week follow-ups.
      CONCLUSIONS: Temporary ectopic implantation of amputated parts provides an
      innovative procedure for the salvage of amputated thumbs under special
      circumstances. Although this procedure is very demanding, it does deserve special
      consideration in reconstructive microsurgery, since it offers the possibility to
      salvage amputated thumbs with extensive soft tissue loss of the hand, by
      preserving the anatomy and restoring the function of severely injured hands.

PMID- 18712845
TI  - Phylogenetic reconstruction of HCV genotype 1b dissemination in a small city
      centre: the Camporeale model.
AB  - Several seroepidemiological population-based surveys carried out in Italy have
      shown a high prevalence of hepatitis C virus (HCV) infection. Camporeale (CP), a
      small Sicilian town with a 10.4% prevalence of HCV mostly genotype 1b, probably
      represents a specific context, since intravenous drug addiction, and sexual
      promiscuity are almost absent. In order to reconstruct the pattern of
      introduction and diffusion of HCV in this ecological niche, the NS5 genomic
      region of 72 HCV genotype 1 isolates (39 from CP and 33 collected throughout
      Sicily) was amplified and sequenced. Sequences were aligned and analyzed by
      BioEdit, PAUP and BEAST, and their molecular evolution compared. Thirty-eight HCV
      genotype 1b isolates from CP were associated in a monophyletic "transmission
      cluster." By applying Monte Carlo Markov simulation, it was calculated that HCV
      was introduced between the end of the 1940s and the beginning of the 1950s. The
      phylogenetic distance between the CP cluster and other Sicilian isolates
      confirmed its uniqueness and the local diffusion from a common ancestor. The data
      obtained from classic phylogenetic analysis, combined with the application of the
      Bayesian analysis to the study of the coalescence of phylogenetic trees, have
      shown that, in CP, few HCV native strains have been transmitted in a limited
      length of time probably through iatrogenic routes, and then have not spread
      further.

PMID- 18712846
TI  - Molecular characterization of genotype 2 and 4 hepatitis C virus isolates in
      French blood donors.
AB  - The subtype distribution of 142 genotype 2 and 97 genotype 4 hepatitis C virus
      (HCV) isolates from the sera of 1,319 volunteer blood donors in France was
      determined by gene sequencing and by phylogenetic analysis of the NS5B region and
      E1 envelope. Findings underlined a wide range of subtypes in both genotypes, that
      is, 20 in HCV-2 and 11 in HCV-4. Eighteen of these 31 subtypes had not been
      defined previously. Some subtypes, that is, 2a, 2b, 2c, 2i, 2k, 4a, and 4d,
      showed numerous strains while subtypes in donors from West Africa or Central
      Africa showed an endemic profile with only a few strains. A Bayesian coalescence
      approach was used to estimate the demographic history of each HCV subtype. The
      estimated mean dates of the most recent common ancestors (MRCA) were 1,889
      (confidence interval (CI), 1,842-1,930) for HCV-2a, 1,886 (CI, 1,843-1,921) for
      HCV-2b, 1,791 (CI, 1,699-1,848) for HCV-2c, 1,846 (CI, 1,803-1,878) for HCV-2i,
      1,911 (CI, 1,879-1,937) for HCV-4a, and 1,957 (CI, 1,943-1,967) for HCV-4d. The
      period of spread for subtype 2b, 2c, and 2i was between 1900 and 1960 whereas
      rapid exponential spread for subtype 2a, 4a, and 4d occurred in the 1960s. The
      inferred histories of population growth indicated that transmission rates
      differed according to HCV subtype. These results may help to predict the future
      burden of HCV in France.

PMID- 18712847
TI  - First report on fatal myocarditis associated with adenovirus infection in Cuba.
AB  - Myocarditis is caused frequently by viral infections of the myocardium. In the
      past, enteroviruses (EV) were considered the most common cause of myocarditis in
      all age groups. Other viruses that cause myocarditis are adenovirus and influenza
      viruses. Parvovirus B19 infection is associated sometimes with myocarditis.
      Members of the Herpesviridae family, cytomegalovirus (CMV), and human herpesvirus
      6 (HHV-6) have been associated occasionally with myocarditis. During an atypical
      outbreak of acute febrile syndrome, eight children, with ages from 5 months to 15
      years, died in cardiogenic shock due to myocarditis in July-August 2005, in the
      city of Havana, Cuba. Nested polymerase chain reaction (nPCR) and nested reverse
      transcription-PCR (nRT-PCR) were carried out on fresh heart muscle and lung
      tissue to analyze the genomic sequences of adenovirus, CMV, HHV-6, herpes simplex
      virus, Epstein-Barr virus (EBV), varizella zoster virus, influenza virus A, B, C,
      respiratory syncytial virus (RSV) A and B, parainfluenza viruses, rhinoviruses,
      coronavirus, flaviruses and enteroviruses. Evidence was for the presence of the
      adenovirus genome in 6 (75%) of the children. Phylogenetic analyses of a
      conserved hexon gene fragment in four cases showed serotype 5 as the causal
      agent. No others viruses were detected. Histological examination was undertaken
      to detect myocardial inflammation. After exclusion of other possible causes of
      death, the results indicated that viral myocarditis was the cause of death in
      patients with adenovirus infection.

PMID- 18712848
TI  - Neutralizing antibody response variation against dengue 3 strains.
AB  - To evaluate the neutralizing antibody activity of a human sera panel against
      seven strains of the homotypic virus. Sera were collected from DENV-3 immune
      individuals. Two DENV-3 genotypes and strains isolated at different time-points
      during the 2000 and 2001-2002 Havana epidemics were included. A panel of 20 late
      convalescent sera collected 16-18 months after acute illness from DF and DHF
      patients are studied. These individuals were infected during the 2001-2002 Havana
      DENV-3 epidemic. All but four sera collected from DF cases had a secondary DENV
      1/DENV-3 infection. Sera neutralizing antibody titer against the seven DENV-3
      strains were determined by plaque reduction neutralization technique. Sera
      samples were tested simultaneously. Studied sera showed higher levels of
      neutralizing antibodies to DENV-3 strains of genotype III compared to genotype V.
      Interesting, higher levels of neutralizing antibodies were detected to DENV-3
      strain isolated at the end of the epidemic 2001-2002. An increased tendency of
      GMT of neutralizing antibodies according to epidemic evolution was observed for
      the 2001-2002 outbreak. In general, antibody levels in sera collected from DF
      cases were higher. Differences in the neutralization capacity of immune DENV-3
      sera tested against two homologous genotypes including strains of the same
      genotype are demonstrated. Observed results suggest that virus changed in the
      course of the epidemic. The implications of this finding in terms of dengue
      pathogenesis and vaccine development need to be considered.

PMID- 18712849
TI  - BT-11 improves stress-induced memory impairments through increment of glucose
      utilization and total neural cell adhesion molecule levels in rat brains.
AB  - In Oriental medicine, roots of Polygala tenuifolia Willdenow have been known to
      be an important herb that exhibits sedative effects in insomnia, palpitation with
      anxiety, restlessness, and disorientation in humans. We previously reported that
      BT-11, extracted from those roots, improved scopolamine-induced amnesia in rats
      and inhibited acetylcholinesterase activities in vitro. Therefore, we proposed
      that BT-11 could remedy stress-induced memory deficits in rats. In this study,
      the stress-induced memory impairments in rats were significantly reversed almost
      to the control level by BT-11 treatment. To seek an active component of BT-11
      that plays an important role in antipsychotic effects, we compared BT-11 with
      3,4,5-trimethoxycinnamic acid (TMCA), which is a constituent of those root
      extracts. However, the effects of TMCA were less or were not consistent with
      those of BT-11 in some of tests. In particular, BT-11 reversed the stress-induced
      reduction of glucose utilization by [(18)fluorodeoxyglucose]FDG-PET and the
      levels of neural cell adhesion molecule (NCAM) in rat brains to the control
      levels, whereas TMCA did not. Therefore, BT-11 improved stress-induced memory
      impairments through increment of glucose utilization and total NCAM levels in rat
      brains. In conclusion, BT-11 may be strongly effective against stress-induced
      amnesia in rats, through the combined effects of TMCA and other active components
      of BT-11.

PMID- 18712850
TI  - Capturing the portrait of isolated individual natural cellulose molecules.
AB  - Natural cellulose molecules have a strong tendency of being aggregated into
      larger structures. Thus, the imaging of isolated individual cellulose molecules
      is hampered for a long time. In this work, we manage to observe, for the first
      time, the isolated individual natural cellulose chains on a sample surface by
      means of atomic force microscope. The advantage of the ionic liquid, in which
      natural cellulose can be molecularly dispersed, is considered to be the key point
      for the successful imaging. Moreover, we find that the surface charge can
      influence the morphology of the single cellulose chains upon adsorption. That is,
      on the positively charged surface, individual cellulose chains adopt an extended
      conformation; whereas on the negatively charged surface, a compact globule
      conformation is observed.

PMID- 18712852
TI  - Inter-residue interactions in protein structures exhibit power-law behavior.
AB  - Inter-residue interactions play an essential role in driving protein folding, and
      analysis of these interactions increases our understanding of protein folding and
      stability and facilitates the development of tools for protein structure and
      function prediction. In this work, we systematically characterized the change of
      inter-residue interactions at various sequence separation cutoffs using two
      protein datasets. The first set included 100 diverse, nonredundant and high
      resolution soluble protein structures, covering all four major structural
      classes, all-alpha, alpha/beta, alpha+beta, and all-beta; and the second set
      included 20 diverse, nonredundant and high-resolution membrane protein
      structures, representing 19 unique superfamilies. It was shown that the average
      number of inter-residue interactions in structures of both datasets displays the
      power-law behavior. Fitting parameters of the power-law function are directly
      related to the structural classes analyzed. These findings provided further
      insight into the distribution of short-, medium-, and long-range inter-residue
      interactions in both soluble and membrane proteins and could be used for protein
      structure prediction.

PMID- 18712851
TI  - Antimicrobial peptide RP-1 structure and interactions with anionic versus
      zwitterionic micelles.
AB  - Topologically, platelet factor-4 kinocidins consist of distinct N-terminal
      extended, C-terminal helical, and interposing gamma-core structural domains. The
      C-terminal alpha-helices autonomously confer direct microbicidal activity, and
      the synthetic antimicrobial peptide RP-1 is modeled upon these domains. In this
      study, the structure of RP-1 was assessed using several complementary techniques.
      The high-resolution structure of RP-1 was determined by NMR in anionic sodium
      dodecyl sulfate (SDS) and zwitterionic dodecylphosphocholine (DPC) micelles,
      which approximate prokaryotic and eukaryotic membranes, respectively. NMR data
      indicate the peptide assumes an amphipathic alpha-helical backbone conformation
      in both micelle environments. However, small differences were observed in the
      side-chain orientations of lysine, tyrosine, and phenylalanine residues in SDS
      versus DPC environments. NMR experiments with a paramagnetic probe indicated
      differences in positioning of the peptide within the two micelle types. Molecular
      dynamics (MD) simulations of the peptide in both micelle types were also
      performed to add insight into the peptide/micelle interactions and to assess the
      validity of this technique to predict the structure of peptides in complex with
      micelles. MD independently predicted RP-1 to interact only peripherally with the
      DPC micelle, leaving its spherical shape intact. In contrast, RP-1 entered deeply
      into and significantly distorted the SDS micelle. Overall, the experimental and
      MD results support a preferential specificity of RP-1 for anionic membranes over
      zwitterionic membranes. This specificity likely derives from differences in RP-1
      interaction with distinct lipid systems, including subtle differences in side
      chain orientations, rather than gross changes in RP-1 structure in the two lipid
      environments.

PMID- 18712853
TI  - Structure and hydration of the amylopectin trisaccharide building blocks-
      Synthesis, NMR, and molecular dynamics.
AB  - To gain insight into the molecular details and hydration of amylopectin, the five
      constituting trisaccharides have been chemically synthesized as their methyl
      alpha-glycosides. All five trisaccharides were subjected to 950 MHz NMR
      spectroscopy for complete assignment and nanosecond molecular dynamics
      trajectories were calculated to study the structure and dynamics of the
      trisaccharides in aqueous solution. Systematic analysis of the simulation data
      revealed several examples of bridging water molecules playing an important role
      in the stabilization of specific amylopectin conformations, which was also
      supported by the experimental NMR data such as interresidue NOE's and
      heteronuclear scalar couplings between nuclei from neighboring residues. Although
      alpha-maltotriose, alpha-iso-maltotriose, alpha-panose and alpha-isopanose are
      relatively well characterized structures, the study also includes one less
      characterized trisaccharide with the structure alphaGlcp(1-->4)alphaGlcp(1-
      >6)alphaGlcp. This trisaccharide, tentatively labelled alpha-forkose, is located
      at the branch point of amylopectin, forking the amylopectin into two strands that
      align into double-helical segments. The results show that the conformation of
      alpha-forkose takes a natural bend form which fits well into the structure of the
      double-helical segment of amylopectin. As the only trisaccharide in this study
      the structure of alpha-forkose is not significantly influenced by the hydration.
      In contrast, alpha-isopanose takes a restricted, but rather extended form due to
      an exceptionally strong localized water density. The two homo-linkage oligomers,
      alpha-maltotriose and alpha-iso-maltotriose, showed to be the most extended and
      the most flexible trimers, respectively, providing regular structure for
      crystalline domains and maximum linker flexibility for amorphous domains.

PMID- 18712854
TI  - Combination of Cobe AutoPBSC and Gambro Elutra as a platform for monocyte
      enrichment in dendritic cell (DC) therapy: clinical study.
AB  - Monocytes are a common source for generating dendritic cells (DCs). The aim of
      the present study was to evaluate the efficiency of a platform for monocyte
      collection and enrichment in a clinical setting. The platform was based on the
      combination of two semiautomated devices; the Cobe Spectra Auto PBSC for
      mononuclear cells (MNC) collection followed by counterflow elutriation for
      monocyte enrichment (Gambro BCT Elutra). Twenty-four patients with various types
      of epithelial cancer participated in the study. MNC collections were first
      performed as large volume leukapheresis (LVL). Subsequently, MNC products were
      processed with an elutriation system for monocyte isolation. LVL resulted in the
      collection of MNC at a median of 8.1 x 10(9) cells, containing of 31.4%
      monocytes. A similar efficacy was also shown in patients with lower peripheral
      blood counts. Elutriation of the MNC product with the Cobe Elutra device resulted
      in the enrichment of monocytes at a median of 2.7 x 10(9) cells, with a recovery
      of 80.2% and a purity of 90.7%. These monocytes were then successfully developed
      into DCs for clinical therapy after in vitro manipulation. These data suggest
      that the combination of the Cobe Spectra Auto PBSC and the Gambro BCT Elutra is
      an effective platform for monocyte enrichment in clinical practice according to
      GCP standards and GMP guidelines, and can be easily implemented in the clinical
      routine under current DC protocols.

PMID- 18712855
TI  - An additional flexor of the fifth digit: flexor digiti minimi longus.

PMID- 18712856
TI  - Bioisosteric replacement of the pyrazole 5-aryl moiety of N-(piperidin-1-yl)-5-(4
      chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
      (SR141716A). A novel series of alkynylthiophenes as potent and selective
      cannabinoid-1 receptor antagonists.
AB  - Replacing the conventional pyrazole 5-aryl substituent of 1 (SR141716A) with the
      2-thienyl moiety appended with an appropriate alkynyl unit, a novel class of 5-(5
      alkynyl-2-thienyl)pyrazole derivatives, behaving as highly potent CB1 receptor
      antagonists with good CB1/2 selectivity, was discovered, many of which, as
      typified by compound 18, showed significant weight reduction in diet-induced
      obese mouse model, thus pharmacologically validating that the bioisosteric
      replacement described above is viable. Also encouraging was the finding that a
      subtle structural modification of the newly developed series could result in a
      distinct difference in the intrinsic property, as demonstrated by compounds 12
      (NA) and its methylated structural isomers 15 (PA) and 18 (IA). Moreover, current
      structure-activity relationship studies revealed that around the pyrazole 5
      position of 1, a deep and flat crevice surrounded by a sequence of
      hydrophobic/aromatic residues as indicated by the CB1-receptor homology model
      might exist in the binding site.

PMID- 18712858
TI  - Free energy calculations on the binding of colchicine and its derivatives with
      the alpha/beta-tubulin isoforms.
AB  - Tubulin is the target for numerous small molecule ligands which alter microtubule
      dynamics leading to cell cycle arrest and apoptosis. Many of these ligands are
      currently used clinically for the treatment of several types of cancer, and they
      bind to one of three distinct binding sites within beta-tubulin (paclitaxel,
      vinca, and colchicine), all of which have been identified crystallographically.
      Unfortunately, serious side effects always accompany chemotherapy since these
      drugs bind to tubulin indiscriminately, leading to the death of both cancerous
      and healthy cells. However, the existence and distribution of divergent tubulin
      isoforms provide a platform upon which we may build novel chemotherapeutic drugs
      that can differentiate between different cell types and therefore reduce
      undesirable side effects. We report results of computational analysis that aims
      at predicting differences between the binding energies of a family of colchicine
      derivatives against 10 human alpha/beta-tubulin isoforms. Free energy
      perturbation method has been used in our calculations and the results provide a
      proof of principle by indicating significant differences both among the
      derivatives and between tubulin isoforms.

PMID- 18712857
TI  - Designed glycopeptides with different beta-turn types as synthetic probes for the
      detection of autoantibodies as biomarkers of multiple sclerosis.
AB  - Circulating autoantibodies have been recognized as disease biomarkers of
      autoimmune diseases. We have previously disclosed a synthetic glycopeptide that
      is able to detect specific autoantibodies in sera of patients who are affected by
      multiple sclerosis (MS). This glycopeptide is characterized by a type I' beta
      turn around the minimal epitope Asn(Glc) that allows an efficient exposure of
      this moiety to antibody interactions in the context of a solid-phase
      immunoenzymatic assay. With the aim of optimizing the glycopeptide-antibody
      interactions, we analyze a series of new glycopeptides based on different turn
      structures. Our results confirm the role of conformation in the recognition and
      binding of synthetic antigenic probes to MS autoantibodies. Glycopeptide 2, which
      is characterized by a type I beta-turn around the minimal epitope Asn(Glc), shows
      the highest antibody affinity (IC50 = 11.8 nM), and thus it appears to be a
      promising tool for the detection of specific autoantibodies as MS biomarker in
      patients' sera.

PMID- 18712859
TI  - Computationally identified novel diphenyl- and phenylpyridine androgen receptor
      antagonist structures.
AB  - We have identified and profiled a set of androgen receptor (AR) binding compounds
      representing two nonsteroidal scaffolds from a public chemical database supplied
      by Asinex with virtual screening procedure incorporating our recently published
      3D QSAR model of AR ligands. The diphenyl- and phenylpyridine-based compounds act
      as antagonists in wild-type AR in CV1 cells and also retain this antagonistic
      character in CV1 cells expressing T877A mutant receptor. This mutation is
      frequently associated with prostate cancer. Two of the compounds repress the
      androgen-dependent cell growth of LNCaP prostate cancer cells expressing the
      T877A AR mutant. Molecular modeling of the observed in vitro antagonism with
      induced fit docking suggests that W741 and M895 could be mechanistically involved
      in the initiation of the antagonism. The results indicate finding of nonsteroidal
      AR antagonist compounds from a public chemical database with computational
      methods. Compounds could serve as a novel platform to develop more potent AR
      antagonists with inhibitory activity in both wild-type and T877A mutant AR.

PMID- 18712860
TI  - Synthesis, structure and magnetic behavior of five-coordinate bis(iminopyrrolyl)
      complexes of cobalt(II) containing PMe3 and THF ligands.
AB  - The new bis-iminopyrrolyl five-coordinate Co(II) complexes [Co(kappa (2) N, N'-NC
      4H 3C(R)N-2,6- (i)Pr 2C 6H 3) 2(PMe 3)] (R = H 3a; Me 3b) were synthesized in
      high yields (ca. 80-90%), using THF and diethyl ether as solvents, respectively,
      by (a) treatment of CoCl 2(PMe 3) 2 with the corresponding iminopyrrolyl Na salts
      ( Ie or If) or (b) reaction of anhydrous CoCl 2 and PMe 3 with Ie or If. A third
      route was tested, involving the addition of excesses of PMe 3 to the complexes
      [Co(kappa (2) N, N'-NC 4H 3C(R)N-2,6- (i)Pr 2C 6H 3) 2] (R = H 1e; Me 1f), which
      was only successful for the synthesis of 3a, in lower yields (ca. 30%). The
      synthesis of 3b in THF was unfruitful because of the kinetic competition of the
      solvent, giving rise to mixtures of 1f and its coordinated THF adduct 4b. The
      synthesis of the new bis-iminopyrrolyl five-coordinate Co(II) complexes [Co(kappa
      (2) N, N'-NC 4H 3C(R)N-2,6- (i)Pr 2C 6H 3) 2(THF)] (R = H 4a; Me 4b) were carried
      out in high yields (ca. 80-90%) by the reaction of CoCl 2(THF) 1.5 with the
      corresponding iminopyrrolyl Na salt. All the compounds have been characterized by
      X-ray diffraction, with 3a and 3b showing axially compressed trigonal bipyramidal
      geometry (with the PMe 3 ligand lying on the equatorial plane), whereas complexes
      4a and 4b exhibit distorted square pyramidal geometries with the THF molecule
      occupying the axial position. Complex 4a shows clearly a compressed geometry, but
      for complex 4b, two polymorphs were characterized, exhibiting molecules with
      different Co-O (THF) bond lengths, one of them being compatible with an elongated
      form. Magnetic measurements either in the solid or in the liquid phases indicate
      that complexes 3a and 3b have low-spin ground states ( S = 1/2). In toluene
      solution, the geometry is fully confirmed by EPR data, which further indicates a
      d x (2) - y (2) /d xy ground state. However, compounds 4a and 4b behave unusually
      because they show magnetic moments that are compatible with high-spin ground
      states ( S = 3/2) in the solid state, but conform to low-spin ground states ( S =
      1/2) when both complexes are dissolved in toluene solutions. The low-spin ground
      states in toluene solution are confirmed by EPR spectroscopy, which further
      supports, for complexes 4a and 4b, an axially elongated square pyramidal geometry
      and a d z (2) ground state. Thus the change in the ground-state and,
      consequently, in the geometry of complexes 4a and 4b from solid state to toluene
      solution might be a consequence of the elongation of the Co-O(THF) bond length.
      DFT studies performed on complexes 3 and 4 corroborate their different structure
      and magnetic behaviors and verify, for the latter complexes, the structural
      differences observed in the solid state and in toluene solution.

PMID- 18712861
TI  - Hybrid organic-inorganic framework structures: influence of cation size on metal
      oxygen-metal connectivity in the alkaline earth thiazolothiazoledicarboxylates.
AB  - We report the synthesis of four organic-inorganic frameworks of alkaline earth
      cations with the organic ligand 2,5-thiazolo[5,4-d]thiazoledicarboxylate
      (C6N2S2O4(2-), Thz(2-)). Structures with remarkably different connectivities
      result when Mg(2+), Ca(2+), Sr(2+), and Ba(2+) react with Thz(2-). Mg(Thz)(H2O)4
      (I) forms a 1-D coordination polymer in which one carboxylate oxygen on each
      terminus of the ligand connects individual MgO6 octahedra from their axial
      positions, while the remaining equatorial sites are coordinated by water
      molecules. Ca2(Thz)2(H2O)8 (II) forms a 1-D coordination polymer in which dimeric
      clusters with 7-fold Ca coordination are connected via the ligand in a linear
      fashion, with a second, uncoordinated Thz(2-) providing charge balance.
      Sr(Thz)(H2O)3 (III) has 1-D infinite inorganic connectivity built from edge
      sharing SrO7N polyhedra having one carboxylate oxygen and one water molecule
      acting as M-O-M bridges. Ba2(Thz)2(H2O)7 (IV) has 2-D inorganic connectivity
      based upon face- and edge-sharing BaO9N polyhedra. One carboxylate oxygen and all
      water molecules act as bridges between each Ba(2+) and its three neighbors. We
      shall discuss the manner in which the increasing coordination requirements of the
      cations (MgO6 < CaO7 < SrO7N < BaO9N) lead to an increase in inorganic
      connectivity through the series.

PMID- 18712862
TI  - The alkylation mechanism of zinc-bound thiolates depends upon the zinc ligands.
AB  - Alkylation of zinc-bound thiolates occurs in both catalytic and structural zinc
      sites of enzymes. Recent biomimetic studies have led to a controversy as to which
      mechanism is operative in thiolate alkylation. Building on one of these
      biomimetic complexes, we have devised a series of models that allow for an
      appraisal of the roles of charge, ligand nature, and hydrogen bonding to sulfur
      on reactivity. The reactions of these complexes with methyl iodide, leading to
      thioethers and zinc iodide complexes, have been examined by density functional
      theory calculations, in the gas phase as well as in an aqueous solution. In all
      cases, a S(N)2 reaction is favored over sigma-bond metathesis. Both the net
      electronic charge and the hydrogen bond play a significant role in the
      nucleophilicity of the thiolate. We find that the mechanistic diversity observed
      experimentally can be explained by the difference in the net charge of the
      complexes. A dianionic complex follows a dissociative pathway, whereas an
      associative one is preferred for a neutral system.

PMID- 18712863
TI  - Synthesis and characterization of bis[bis(pentafluoroethyl)phosphinyl]imides,
      M(+)N[(C2F5)2P(O)]2(-), M = H, Na, K, Cs, Ag, Me4N.
AB  - A convenient synthesis and a full characterization of the strong acid
      bis[bis(pentafluoroethyl)phosphinyl]imide and some of its salts M (+)N[(C 2F 5)
      2P(O)] 2 (-), M = Na, K, Cs, Ag, Me 4N, are presented. Their thermal (mp, T dec.)
      and spectroscopic (IR, Raman, NMR) properties are discussed. A single crystal
      structure of [Me 4N][N{P(O)(C 2F 5) 2} 2] has been obtained, and the structural
      parameters of the anion are compared with the results of quantum-chemical
      calculations. The observed properties are comparable to those of
      bis((trifluoromethyl)sulfonyl)imide and their derivatives.

PMID- 18712864
TI  - Polypeptide friction and adhesion on hydrophobic and hydrophilic surfaces: a
      molecular dynamics case study.
AB  - Using all-atomistic MD simulations including explicit water, the mobility and
      adhesion of a mildly hydrophobic single polypeptide chain adsorbed on hydrophobic
      and hydrophilic diamond surfaces is investigated by application of lateral and
      vertical pulling forces. Forced motion on the hydrophilic surface exhibits stick
      slip due to breaking and reformation of hydrogen bonds; in contrast, on the
      hydrophobic surface, the motion is smooth. By carefully tuning the driving force
      magnitude, the linear-response regime is reached on a hydrophobic surface and
      equilibrium values for mobility and adhesive strength are obtained. On the
      hydrophilic surface, on the other hand, slow hydrogen-bond kinetics prevents
      equilibration and only upper bounds for adhesion force and mobility can be
      estimated. Whereas the desorption force is rather comparable on the two surfaces
      and differs at most by a factor of 2, the mobility on the hydrophilic surface is
      at least 30-fold reduced compared to the hydrophobic one. A simple model based on
      a single particle diffusing in a corrugated potential landscape suggests that
      cooperativity is rather limited and that the small mobility on a hydrophilic
      surface can be rationalized in terms of incoherently moving monomers. The
      experimentally well-known peptide mobility in bulk water is quantitatively
      reproduced in our simulations, which serves as a sensitive test on our
      methodology employed.

PMID- 18712865
TI  - Mesitylboron-substituted ladder-type pentaphenylenes: charge-transfer, electronic
      communication, and sensing properties.
AB  - A series of dimesitylboron (B)- or ditolylamino (N)-substituted ladder-type
      pentaphenylenes (PP) has been designed and synthesized. The UV-vis absorption
      spectra of compounds BPPN, BPPB, and NPPN reveal an identical maximum wavelength
      at 432 nm, which indicates that the B and N centers have very similar
      contributions to the extended conjugation. A rather weak solvatochromism in the
      UV-vis absorption spectra is observed for compound BPPN, while a remarkable
      solvatochromic emission is achieved even though the distance between the B and
      the N centers is as huge as 22 A. The photoluminescence of BPPN shows a
      bathochromic shift of 108 nm when the solvent polarity is increased from
      cyclohexane (453 nm) to acetone (561 nm). Compound BPPN acts as a colorimetric
      and fluorescent chemosensor with high sensitivity (10(-5) M) and selectivity for
      F(-) over other halogen ions. By inhibiting the charge transfer (CT) from the N
      center to the B center, the intense green CT emission of compound BPPN rapidly
      switches into the sky-blue emission of PP when F(-) is bound to the B center.
      Furthermore, a CT emission can be switched "on" and "off" when compound BPPB is
      used as F(-) sensory material. Such an intramolecular CT emission between the two
      B centers has so far never been reported. Corresponding studies by cyclic
      voltammetry and differential pulse voltammetry reveal a two-step reduction of the
      two bridged B centers in compound BPPB, which might suggest that the charge
      delocalizes through the whole molecule and that the terminal redox centers
      communicate through the pentaphenylene bridge.

PMID- 18712866
TI  - Assigning vibrational spectra of ferryl-oxo intermediates of cytochrome C oxidase
      by periodic orbits and molecular dynamics.
AB  - Complexity is inherent in biological molecules not only because of the large
      number of atoms but also because of their nonlinear interactions responsible for
      chaotic behaviours, localized motions, and bifurcation phenomena. Thus, versatile
      spectroscopic techniques have been invented to achieve temporal and spatial
      resolution to minimize the uncertainties in assigning the spectra of complex
      molecules. Can we associate spectral lines to specific chemical bonds or species
      in a large molecule? Can energy stay localized in a bond for a substantial period
      of time to leave its spectroscopic signature? These longstanding problems are
      investigated by studying the resonance Raman spectra of ferryl-oxo intermediates
      of cytochrome c oxidase. The difference spectra of isotopically substituted
      ferryl oxygen ((16)O minus (18)O) in the cytochrome c oxidase recorded in several
      laboratories show one or two prominent positive peaks which have not been
      completely elucidated yet. By applying the hierarchical methods of nonlinear
      mechanics, and particularly the study of periodic orbits in the active site of
      the enzyme, in conjunction with molecular dynamics calculations of larger systems
      which include the embraced active site by the protein and selected
      protonated/deprotonated conformations of amino acids, we translate the spectral
      lines to molecular motions. It is demonstrated that for the active site stable
      periodic orbits exist for a substantial energy range. Families of periodic orbits
      which are associated with the vibrations of Fe(IV)=O bond mark the regions of
      phase space where nearby trajectories remain localized, as well as assign the
      spectral bands of the active site in the protein matrix. We demonstrate that
      proton movement adjacent to active site, which occurs during the P --> F
      transition, can lead to significant perturbations of the Fe(IV)=O isotopic
      difference vibrational spectra in cytochrome c oxidase, without a change in
      oxidation state of the metal sites. This finding links spectroscopic
      characteristics to protonation events occurring during enzymatic turnover.

PMID- 18712867
TI  - Quantitative microarray analysis of intact glycolipid-CD1d interaction and
      correlation with cell-based cytokine production.
AB  - The protein CD1d binds self and foreign glycolipids for presentation to CD1
      restricted T cells by means of TCR recognition and activates T(H)1 and T(H)2
      chemokine release. In this study, a variety of glycolipid ligands were attached
      to a microarray surface and their binding with dimeric CD1d was investigated. An
      alpha-galactosyl ceramide (alpha-GalCer) bearing a carbamate group at the 6'-OH
      position was tethered to the surface, and the dissociation constant on surface
      with CD1d was determined to reflect the multivalent interaction. Competition
      assays were then used to determine the dissociation constants (Ki) of new and
      intact glycolipids in solution. The 4-fluorophenyloctanoyl-modified alpha-GalCer
      (18) was found to bind most strongly with CD1d (Ki 0.21 microM), 2 orders of
      magnitude stronger than alpha-GalCer and more than three times more selective
      than alpha-GalCer for IFN-gamma release from NKT cells. Various alpha-GalCer
      analogues were analyzed, and the results showed that the binding affinity of
      glycolipids to CD1d correlates well with IFN-gamma production but poorly with IL
      4 secretion by NKT cells, suggesting that tighter binding ligands could bias
      cytokine release through the T(H)1 pathway.

PMID- 18712868
TI  - Quantum chemical study of Lewis acid catalyzed allylboration of aldehydes.
AB  - The reaction rate enhancement in the reaction of allylboronate with benzaldehyde
      in the presence of AlCl3 has been studied theoretically. B3LYP calculations find
      a relatively high activation barrier for the reaction of pinacol allylboronate
      with benzaldehyde in the absence of the Lewis acid. The reaction paths that go
      through the transition states coordinated by an AlCl3 molecule at one of the two
      oxygen atoms in the boronate give significantly lower values of activation
      energy. An analysis of electron populations and orbitals taking part in bond
      formation indicates that the AlCl3 molecule attached to the boronate oxygen atom
      strengthens the electrophilicity of the boron center, while it weakens the
      nucleophilicity of the C(gamma)-C(beta) bond. The result supports the
      electrophilic boronate activation mechanism proposed by Rauniyar and Hall on the
      basis of experiments and kinetic studies. In contrast, the reaction path in which
      AlCl3 is coordinated to the carbonyl oxygen of benzaldehyde shows a higher
      activation barrier, though the initial reactant complex is more stable than those
      in other reaction paths. The AlCl3 molecule reduces the reactivity of aldehyde by
      depressing the nucleophilicity of the sigma-type lone pair of electrons on the
      carbonyl oxygen, though the electrophilicity of the carbonyl pi orbital is
      strengthened to some extent. The significance of charge polarization within
      allylboronate in enhancing the reactivity of boron by the Lewis acid is
      discussed.

PMID- 18712869
TI  - Nitroxide paramagnet-induced para-ortho conversion and nuclear spin relaxation of
      H2 in organic solvents.
AB  - The kinetics of para-ortho conversion and nuclear spin relaxation of H 2 in
      chloroform- d 1 were investigated in the presence of nitroxides as paramagnetic
      catalysts. The back conversion from para-hydrogen ( p-H 2) to ortho-hydrogen ( o
      H 2) was followed by NMR by recording the increase in the intensity of the signal
      of o-H 2 at regular intervals of time. The nitroxides proved to be hundreds of
      times more effective at inducing relaxation among the spin levels of o-H 2 than
      they are in bringing about transitions between p-H 2 and the levels of o-H 2. The
      value of the encounter distance d between H 2 and the paramagnetic molecule,
      calculated from the experimental bimolecular conversion rate constant k 0, using
      the Wigner theory of para-ortho conversion, agrees perfectly with that calculated
      from the experimental relaxivity R 1 using the force free diffusion theory of
      spin-lattice relaxation.

PMID- 18712871
TI  - Transition from complete to partial wetting within membrane compartments.
AB  - Wetting and dewetting phenomena are ubiquitous, but wetting transitions have been
      reported only in a few experimental systems. In this work, we present a wetting
      transition in a mesoscopic membrane compartment for the first time. A two-phase
      aqueous polymer solution was encapsulated in a giant vesicle (few tens of
      micrometers in size). The polymers used are poly(ethyleneglycol) (PEG) and
      dextran. By increasing the polymer concentration in the vesicle, the PEG-rich
      phase changed from complete wetting to partial wetting of the membrane.

PMID- 18712870
TI  - Density functional theory study on a missing piece in understanding of heme
      chemistry: the reaction mechanism for indoleamine 2,3-dioxygenase and tryptophan
      2,3-dioxygenase.
AB  - Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are heme
      containing dioxygenases and catalyze oxidative cleavage of the pyrrole ring of L
      tryptophan. On the basis of three recent crystal structures of these heme
      containing dioxygenases, two new mechanistic pathways were proposed by several
      groups. Both pathways start with electrophilic addition of the Fe(II)-bound
      dioxygen concerted with proton transfer (oxygen ene-type reaction), followed by
      either formation of a dioxetane intermediate or Criegee-type rearrangement.
      However, density functional theory (DFT) calculations do not support the proposed
      concerted oxygen ene-type and Criegee-type rearrangement pathways. On the basis
      of DFT calculations, we propose a new mechanism for dioxygen activation in these
      heme systems. The mechanism involves (a) direct electrophilic addition of the
      Fe(II)-bound oxygen to the C2 or C3 position of the indole in a closed-shell
      singlet state or (b) direct radical addition of the Fe(III)-superoxide to the C2
      position of the indole in a triplet (or open-shell singlet) state. Then, a
      radical-recombination or nearly barrierless charge-recombination step from the
      resultant diradical or zwitterionic intermediates, respectively, proceeds to
      afford metastable dioxetane intermediates, followed by ring-opening of the
      dioxetanes. Alternatively, homolytic O-O bond cleavage from the diradical
      intermediate followed by oxo attack and facile C2-C3 bond cleavage could compete
      with the dioxetane formation pathway. Effects of ionization of the imidazole and
      negatively charged oxyporphyrin complex on the key dioxygen activation process
      are also studied.

PMID- 18712872
TI  - Total synthesis of chlorofusin, its seven chromophore diastereomers, and key
      partial structures.
AB  - Chlorofusin is a recently isolated, naturally occurring inhibitor of p53-MDM2
      complex formation whose structure is composed of a densely functionalized
      azaphilone-derived chromophore linked through the terminal amine of ornithine to
      a nine residue cyclic peptide. Herein we report the full details of the total
      synthesis of chlorofusin, resulting in the assignment of the absolute
      stereochemistry and reassignment of the relative stereochemistry of the complex
      chromophore. Condensation of each enantiomer of an azaphilone chromophore
      precursor with the N(delta)-amine of a protected ornithine-threonine dipeptide,
      followed by a one-step oxidation/spirocyclization of the most reactive olefin
      provided all eight diastereomers of the fully elaborated chromophore-dipeptide
      conjugate. Comparison of the spectroscopic properties for these eight compounds
      and those of simpler models with that reported for the natural product allowed
      the full assignment of the (4R,8S,9R)-stereochemistry of the chlorofusin
      chromophore. The natural, but stereochemically reassigned, diastereomer of the
      dipeptide conjugate was incorporated in a convergent total synthesis of
      chlorofusin confirming the stereochemical reassignment and establishing its
      absolute stereochemistry. Similarly and enlisting the late stage convergent point
      in the total synthesis, the remaining seven diastereomers of the chromophore
      dipeptide conjugates were individually incorporated into the nine-residue cyclic
      peptide of chlorofusin (4 steps each) providing all seven remaining possible
      chromophore diastereomers of the natural product.

PMID- 18712873
TI  - Axial ligand effects on the geometric and electronic structures of nonheme
      oxoiron(IV) complexes.
AB  - A series of complexes [Fe(IV)(O)(TMC)(X)](+) (where X = OH(-), CF3CO2(-), N3(-),
      NCS(-), NCO(-), and CN(-)) were obtained by treatment of the well-characterized
      nonheme oxoiron(IV) complex [Fe(IV)(O)(TMC)(NCMe)](2+) (TMC = tetramethylcyclam)
      with the appropriate NR4X salts. Because of the topology of the TMC macrocycle,
      the [Fe(IV)(O)(TMC)(X)](+) series represents an extensive collection of S = 1
      oxoiron(IV) complexes that only differ with respect to the ligand trans to the
      oxo unit. Electronic absorption, Fe K-edge X-ray absorption, resonance Raman, and
      Mossbauer data collected for these complexes conclusively demonstrate that the
      characteristic spectroscopic features of the S = 1 Fe(IV)=O unit, namely, (i) the
      near-IR absorption properties, (ii) X-ray absorption pre-edge intensities, and
      (iii) quadrupole splitting parameters, are strongly dependent on the identity of
      the trans ligand. However, on the basis of extended X-ray absorption fine
      structure data, most [Fe(IV)(O)(TMC)(X)](+) species have Fe=O bond lengths
      similar to that of [Fe(IV)(O)(TMC)(NCMe)](2+) (1.66 +/- 0.02 A). The mechanisms
      by which the trans ligands perturb the Fe(IV)=O unit were probed using density
      functional theory (DFT) computations, yielding geometric and electronic
      structures in good agreement with our experimental data. These calculations
      revealed that the trans ligands modulate the energies of the Fe=O sigma- and pi
      antibonding molecular orbitals, causing the observed spectroscopic changes. Time
      dependent DFT methods were used to aid in the assignment of the intense near-UV
      absorption bands found for the oxoiron(IV) complexes with trans N3(-), NCS(-),
      and NCO(-) ligands as X(-)-to-Fe(IV)=O charge-transfer transitions, thereby
      rationalizing the resonance enhancement of the nu(Fe=O) mode upon excitation of
      these chromophores.

PMID- 18712875
TI  - C-C bond-forming desulfurizations of sulfoximines.
AB  - Highly substituted, enantiomerically pure azaheterocyclic ring systems play an
      important role in medicinal chemistry as potential peptide mimetics. Metalated 2
      alkenyl sulfoximines offer an efficient entry to this class of compounds. In this
      paper, we describe a new means to remove the sulfonimidoyl auxiliary with
      concomitant formation of a C-C double bond.

PMID- 18712874
TI  - Lipid-rhodopsin hydrophobic mismatch alters rhodopsin helical content.
AB  - The ability of photoactivated rhodopsin to achieve the enzymatically active
      metarhodopsin II conformation is exquisitely sensitive to bilayer hydrophobic
      thickness. The sensitivity of rhodopsin to the lipid matrix has been explained by
      the hydrophobic matching theory, which predicts that lipid bilayers adjust
      elastically to the hydrophobic length of transmembrane helices. Here, we examined
      if bilayer thickness adjusts to the length of the protein or if the protein
      alters its conformation to adapt to the bilayer. Purified bovine rhodopsin was
      reconstituted into a series of mono-unsaturated phosphatidylcholines with 14-20
      carbons per hydrocarbon chain. Changes of hydrocarbon chain length were measured
      by (2)H NMR, and protein helical content was quantified by synchrotron radiation
      circular dichroism and conventional circular dichroism. Experiments were
      conducted on dark-adapted rhodopsin, the photo-intermediates metarhodopsin
      I/II/III, and opsin. Changes of bilayer thickness upon rhodopsin incorporation
      and photoactivation were mostly absent. In contrast, the helical content of
      rhodopsin increased with membrane hydrophobic thickness. Helical content did not
      change measurably upon photoactivation. The increases of bilayer thickness and
      helicity of rhodopsin are accompanied by higher metarhodopsin II/metarhodopsin I
      ratios, faster rates of metarhodopsin II formation, an increase of tryptophan
      fluorescence, and higher temperatures of rhodopsin denaturation. The data suggest
      a surprising adaptability of this G protein-coupled membrane receptor to
      properties of the lipid matrix.

PMID- 18712876
TI  - Dearomatizing anionic cyclization of phosphonamides. A route to phosphonic acid
      derivatives with antitumor properties.
AB  - Deprotonation of bis(N-benzyl-N-methyl)-P-arylphosphonic diamides with s-BuLi in
      THF at -90 degrees C takes place selectively at the benzylic position. The anions
      undergo intramolecular attack to the P-aryl ring leading to dearomatized species
      that were trapped with a series of electrophiles (MeOH, ArOH, BnBr, aliphatic and
      aromatic aldehydes, and benzophenone) in very high yield, and with high regio-
      and stereocontrol. The dearomatized products were smoothly transformed into gamma
      aminophosphonic acids under acidic conditions. Preliminary screening for
      antitumor activity showed promising levels of activity.

PMID- 18712877
TI  - Synthesis and properties of butyl-capped dehydrothieno[14]annulenes and their
      conversion into terthiophenes.
AB  - A series of butyl end-capped dehydrothieno[14]annulenes (DTAs) has been prepared.
      These compounds were further transformed into electron-rich terthiophenes (3TPs)
      by reaction with sodium sulfide. The DTA and 3TP macrocycles were compared
      qualitatively using UV-vis spectroscopy, and the latter were found to have lower
      energy absorptions. The conformations of these molecules were also examined by
      DFT-YFLP computations.

PMID- 18712878
TI  - Degradation of flumorph in soils, aqueous buffer solutions, and natural waters.
AB  - Flumorph is an oomycete fungicide that is now used extensively in China. A
      residue analysis method for the determination of flumorph in environmental
      samples was developed with solid-phase extraction (SPE) for sample preparation
      and high-performance liquid chromatographic (HPLC) for separation. An
      environmental fate study was performed concerning the degradation of flumorph in
      soils, aqueous buffer solutions, and natural waters under laboratory-controlled
      conditions. The degradation of flumorph in three Chinese soil samples followed a
      first-order kinetics, with half-lives all longer than 100 days. No degradation of
      flumorph occurred in aqueous buffer solutions having different pH values or in
      natural waters with different physical and chemical properties. The data
      generated from this study could be helpful for risk assessment studies of the
      pesticide in the environment.

PMID- 18712879
TI  - Effects of nitrogen fertilization on the phenolic composition and antioxidant
      properties of basil (Ocimum basilicum L.).
AB  - Many herbs and spices have been shown to contain high levels of polyphenolic
      compounds with potent antioxidant properties. In the present study, we explore
      how nutrient availability, specifically nitrogen fertilization, affects the
      production of polyphenolic compounds in three cultivars (Dark Opal, Genovese, and
      Sweet Thai) of the culinary herb, basil ( Ocimum basilicum L.). Nitrogen
      fertilization was found to have a significant effect on total phenolic levels in
      Dark Opal ( p < 0.001) and Genovese ( p < 0.001) basil with statistically higher
      phenolic contents observed when nutrient availability was limited at the lowest
      (0.1 mM) applied nitrogen treatment. Similarly, basil treated at the lowest
      nitrogen fertilization level generally contained significantly higher rosmarinic
      ( p = 0.001) and caffeic ( p = 0.001) acid concentrations than basil treated at
      other nitrogen levels. Nitrogen fertilization also affected antioxidant activity
      ( p = 0.002) with basil treated at the highest applied nitrogen level, 5.0 mM,
      exhibiting lower antioxidant activity than all other nitrogen treatments. The
      anthocyanin content of Dark Opal basil was not affected by applied nitrogen
      level, but anthocyanin concentrations were significantly impacted by growing
      season ( p = 0.001). Basil cultivar was also determined to have a statistically
      significant effect on total phenolic levels, rosmarinic and caffeic acid
      concentrations, and antioxidant activities.

PMID- 18712880
TI  - Simultaneous determination of hydrolysis and mutarotation rates during the
      enzymatic hydrolysis of lactose.
AB  - An experiment is described in which a custom-made glucose electrode is used to
      directly monitor the enzymatic hydrolysis of lactose to glucose. The transient
      profile of beta- d-glucose can be used to simultaneously determine the rate
      constants for mutarotation and for enzymatic hydrolysis by applying a dynamic
      nonlinear regression routine. Due to differences in the mutarotation rate
      constants between lactose and glucose, the beta- d-glucose concentration
      "overshoots" equilibrium under certain conditions, which can be modeled
      mathematically. This overshoot can be observed reliably and used to quantify the
      differences in mutarotational equilibria between glucose and lactose. These
      observations may be important for the analysis of dairy products and commercial
      lactase preparations and illustrate an unusual kinetic phenomenon caused by
      intramolecular forces. This approach may also be important for the accurate
      determination of a variety of oligosaccharides such as glycogen, which tend to be
      composed primarily of one stereoisomer.

PMID- 18712881
TI  - Intramolecular electron transfer versus substrate oxidation in lactoperoxidase:
      investigation of radical intermediates by stopped-flow absorption
      spectrophotometry and (9-285 GHz) electron paramagnetic resonance spectroscopy.
AB  - We have combined the information obtained from rapid-scan electronic absorption
      spectrophotometry and multifrequency (9-295 GHz) electron paramagnetic resonance
      (EPR) spectroscopy to unequivocally determine the electronic nature of the
      intermediates in milk lactoperoxidase as a function of pH and to monitor their
      reactivity with organic substrates selected by their different accessibilities to
      the heme site. The aim was to address the question of the putative catalytic role
      of the protein-based radicals. This experimental approach allowed us to
      discriminate between the protein-based radical intermediates and [Fe(IV)=O]
      species, as well as to directly detect the oxidation products by EPR. The
      advantageous resolution of the g anisotropy of the Tyr (*) EPR spectrum at high
      fields showed that the tyrosine of the [Fe(IV)=O Tyr (*)] intermediate has an
      electropositive and pH-dependent microenvironment [g(x) value of 2.0077(0) at pH
      >or= 8.0 and 2.0066(2) at 4.0 <or= pH <or= 7.5] possibly related to the radical
      stability and function. Two types of organic molecules (small aromatic vs bulkier
      substrates) allowed us to distinguish different mechanisms for substrate
      oxidation. [Fe(IV)=O Por (*+)] is the oxidizing species of benzohydroxamic acid,
      o-dianisidine, and o-anisidine via a heme-edge reaction and of mitoxantrone via a
      long-range electron transfer (favored at pH 8) not involving the tyrosyl radical,
      the formation of which competed with the substrate oxidation at pH 5. In
      contrast, the very efficient reaction with ABTS at pH 5 is consistent with
      [Fe(IV)=O Tyr (*)] being the oxidizing species. Accordingly, the identification
      of the ABTS binding site by X-ray crystallography may be a valuable tool in
      rational drug design.

PMID- 18712883
TI  - Methods for describing the electromagnetic properties of silver and gold
      nanoparticles.
AB  - This Account provides an overview of the methods that are currently being used to
      study the electromagnetics of silver and gold nanoparticles, with an emphasis on
      the determination of extinction and surface-enhanced Raman scattering (SERS)
      spectra. These methods have proven to be immensely useful in recent years for
      interpreting a wide range of nanoscience experiments and providing the capability
      to describe optical properties of particles up to several hundred nanometers in
      dimension, including arbitrary particle structures and complex dielectric
      environments (adsorbed layers of molecules, nearby metal films, and other
      particles). While some of the methods date back to Mie's celebrated work a
      century ago, others are still at the forefront of algorithm development in
      computational electromagnetics. This Account gives a qualitative description of
      the physical and mathematical basis behind the most commonly used methods,
      including both analytical and numerical methods, as well as representative
      results of applications that are relevant to current experiments. The analytical
      methods that we discuss are either derived from Mie theory for spheres or from
      the quasistatic (Gans) model as applied to spheres and spheroids. In this
      discussion, we describe the use of Mie theory to determine electromagnetic
      contributions to SERS enhancements that include for retarded dipole emission
      effects, and the use of the quasistatic approximation for spheroidal particles
      interacting with dye adsorbate layers. The numerical methods include the discrete
      dipole approximation (DDA), the finite difference time domain (FDTD) method, and
      the finite element method (FEM) based on Whitney forms. We discuss applications
      such as using DDA to describe the interaction of two gold disks to define
      electromagnetic hot spots, FDTD for light interacting with metal wires that go
      from particle-like plasmonic response to the film-like transmission as wire
      dimension is varied, and FEM studies of electromagnetic fields near cubic
      particles.

PMID- 18712882
TI  - Alkyltransferase-mediated toxicity of 1,3-butadiene diepoxide.
AB  - Human O(6)-alkylguanine-DNA alkyltransferase (hAGT) expression increases
      mutations and cytotoxicity following exposure to 1,3-butadiene diepoxide (BDO),
      and hAGT-DNA cross-links are formed in the presence of BDO. We have used hAGT
      mutants to investigate the mechanism of cross-link formation and genotoxicity.
      Formation of a hAGT-DNA conjugate in vitro was observed with C145S and C145A
      mutant proteins but was considerably diminished with the C145A/C150S double
      mutant confirming that cross-linking primarily involves either of these two
      cysteine residues, which are located in the active site pocket of the protein.
      Cross-link formation by BDO occurred both via (a) an initial reaction of BDO with
      hAGT followed by attack of the reactive hAGT complex on DNA, and (b) the initial
      reaction of BDO with DNA followed by a reaction between hAGT and the DNA adduct.
      These results differ from those with 1,2-dibromoethane (DBE) where Cys(145) is
      the only site of attachment and pathway (b) does not occur. The complex formed
      between hAGT at Cys(145) and BDO was very unstable in aqueous solution. However,
      the BDO-hAGT complex at Cys(150) exhibited stability for more than 1 h. The
      effect of hAGT and mutants on BDO-induced genotoxicity was studied in E. coli
      using the forward assay to rifampicin resistance. Both mutations and cell killing
      were greatly increased by wild type hAGT, and there was a smaller but significant
      effect with the C145A mutant. The R128A mutant and R128A/C145A and C145A/C150S
      double mutants were ineffective, supporting the hypothesis that the formation of
      hAGT-DNA cross-links is responsible for the enhanced genotoxicity detected in
      this biological system. In the absence of hAGT, there were equal proportions of
      G:C to A:T transitions, G:C to T:A transversions, and A:T to T:A transversions.
      Wild type hAGT expression yielded significantly greater G:C to A:T and A:T to G:C
      transitions, whereas C145A mutant expression resulted in more transitions and
      transversions at A:T base-pairs.

PMID- 18712884
TI  - Gold nanoparticles in biology: beyond toxicity to cellular imaging.
AB  - Gold, enigmatically represented by the target-like design of its ancient
      alchemical symbol, has been considered a mystical material of great value for
      centuries. Nanoscale particles of gold now command a great deal of attention for
      biomedical applications. Depending on their size, shape, degree of aggregation,
      and local environment, gold nanoparticles can appear red, blue, or other colors.
      These visible colors reflect the underlying coherent oscillations of conduction
      band electrons ("plasmons") upon irradiation with light of appropriate
      wavelengths. These plasmons underlie the intense absorption and elastic
      scattering of light, which in turn forms the basis for many biological sensing
      and imaging applications of gold nanoparticles. The brilliant elastic light
      scattering properties of gold nanoparticles are sufficient to detect individual
      nanoparticles in a visible light microscope with approximately 10(2) nm spatial
      resolution. Despite the great excitement about the potential uses of gold
      nanoparticles for medical diagnostics, as tracers, and for other biological
      applications, researchers are increasingly aware that potential nanoparticle
      toxicity must be investigated before any in vivo applications of gold
      nanoparticles can move forward. In this Account, we illustrate the importance of
      surface chemistry and cell type for interpretation of nanoparticle cytotoxicity
      studies. We also describe a relatively unusual live cell application with gold
      nanorods. The light-scattering properties of gold nanoparticles, as imaged in
      dark-field optical microscopy, can be used to infer their positions in a living
      cell construct. Using this positional information, we can quantitatively measure
      the deformational mechanical fields associated with living cells as they push and
      pull on their local environment. The local mechanical environment experienced by
      cells is part of a complex feedback loop that influences cell metabolism, gene
      expression, and migration.

PMID- 18712885
TI  - Single-crystal-to-single-crystal topochemical polymerizations by design.
AB  - The polymerization of simple conjugated dienes has long been of interest:
      polydienes occur throughout Nature, and polyisoprene and its analogues form the
      basis of entire industries. In contrast, the polymers of similar small conjugated
      compounds, diacetylenes, trienes, and triacetylenes, are either unknown or
      laboratory curiosities. For 40 years, the only viable synthetic method for the
      1,4-polymerization of a diacetylene was a topochemical polymerization in a
      condensed phase. But such an approach is hit or miss: if the diacetylene monomers
      have a solid-state structure preorganized at distances matching the repeat
      distance in the final polymer, then thermal or photochemical energy can bring
      about the polymerization. However, most monomers lack the proper structural
      parameters and simply do not react. As discussed in this Account, we have
      developed a supramolecular host-guest strategy that imposes the necessary
      structural parameters upon a diacetylene monomer that otherwise does not
      polymerize. We apply this strategy in the synthesis of new types of conjugated
      polymers made from diacetylenes, triacetylenes, and trienes. To implement the
      host-guest strategy, we chose a host that would self-assemble into a
      supramolecular structure with the requisite intermolecular spacing. For
      diacetylenes, the ideal spacing is 4.9 A, and the oxalamides, which routinely
      crystallize with a spacing of 5 A, make ideal host molecules. We chose specific
      oxalamide host substituents that bind to the diacetylene guest molecule,
      typically through hydrogen bonding. We have focused upon the single-crystal-to
      single-crystal polymerizations, allowing us to obtain and characterize the
      polymers in perfect crystalline form and to define and better understand the
      reaction trajectories. We have prepared several new classes of polydiacetylenes
      using this strategy, including the first terminal polydiacetylenes and an aryl
      substituted diacetylene. Interestingly, to prepare poly(diiododiacetylene), we
      used halogen bonds to bind the host and guest. The simplest polydiacetylene
      known, poly(diiododiacetylene), lacks the side chains that complicate the
      structures of similar previous polymers. Future studies should provide insights
      into the role of such side chains in conjugated materials. We further
      demonstrated the strength of the host-guest strategy by moving from the
      polydiacetylenes to the polytriacetylenes. Although the structural requirements
      for a triacetylene polymerization had been stated decades ago, no one had ever
      found a triacetylene with the requisite spacing of 7.4 A. We designed a series of
      pyridine-substituted vinylogous amide hosts to achieve this spacing.
      Cocrystallization of these host molecules with a triacetylene dicarboxylic acid
      gave us the desired structure. Using thermal annealing, we completed the
      synthesis of the triacetylene polymer.

PMID- 18712886
TI  - Spontaneous formation of bilayers and vesicles in mixtures of single-chain alkyl
      carboxylates: effect of pH and aging and cytotoxicity studies.
AB  - We report the observation of bilayer fragments, some of which close to form
      vesicles, over a large range of pH at room temperature from mixtures of single
      chain biocompatible commercially available nontoxic alkyl carboxylic surfactants
      after neutralization with HCl. The pH at which the morphological transitions
      occur is varied only by changing the ratio between two surfactants: the
      alkyloligoethyleneoxide carboxylate and sodium laurate. The effect of aging of
      the mixed surfactant systems in the pH region desired for dermatologic
      application (4.5 < pH < 7) is also studied. Finally, we show results of
      cytotoxicity studies on the surfactant mixtures.

PMID- 18712887
TI  - Contact angles of oils on solid substrates in aqueous media: correlation with AFM
      data on protein adhesion.
AB  - This study presents a method to measure the contact angles of oils on a substrate
      in water. Diiodomethane and perfluorodecalin were used as model oils. Self
      assembled monolayers (SAMs) were prepared by adjusting the mole ratio of CH 3-
      and OH-terminated alkanethiols. The contact angles of the two oils in water
      increased with increasing hydrophilicity of the SAMs, and the results are
      contrasted with the contact angles of oils on these surfaces in air. In addition,
      perfluorodecalin showed higher contact angles than diiodomethane on the same
      surface. On the poly(N-isopropylacrylamide) (PNiPAAM) monolayer surface, the
      contact angles of the two oils in water decreased sharply at the transition
      temperature of PNiPAAM (approximately 30 degrees C), but the surface retained
      fairly high hydrophilicity even after the transition. The above results are
      correlated with atomic force microscopy (AFM) measurements of the adhesion force
      between protein-immobilized AFM tips (human fibrinogen and bovine serum albumin)
      and these monolayers.

PMID- 18712888
TI  - Probing Au nanoparticle uptake by enzyme following the digestion of a starch-Au
      nanoparticle composite.
AB  - In this letter, we report on the digestion of starch, when present as a composite
      with Au nanoparticles (NPs), by alpha-amylase. It has been observed that the rate
      of digestion of free starch and that in the composite were identical. Also, the
      well-established iodine test could be carried out to investigate the kinetics in
      the presence of Au NPs. The investigations revealed that following the digestion
      of starch in the composite the NPs were released and subsequently attached to the
      enzyme only and not to the degraded products of starch. Also, the enzyme attached
      to NPs, following digestion, retained its catalytic activity. The particle sizes
      of the NPs were not affected in the process because no agglomeration was
      observed. Experimental observations indicated the possibility of oriented
      attachment of alpha-amylase to the NPs in comparison to amyloglucosidase, another
      digestive enzyme. Finally, we observed a change in the surface plasmon resonance
      (SPR) of the NPs following the digestion of starch in the composite, and thus we
      could demonstrate that the SPR of the NPs could be used as a direct probe for
      monitoring the digestion of the composite by the enzyme.

PMID- 18712889
TI  - AFM studies of solid-supported lipid bilayers formed at a Au(111) electrode
      surface using vesicle fusion and a combination of Langmuir-Blodgett and Langmuir
      Schaefer techniques.
AB  - Atomic force microscopy (AFM) has been used to characterize the formation of a
      phospholipid bilayer composed of 1,2-dimyristyl-sn-glycero-3-phosphocholine
      (DMPC) at a Au(111) electrode surface. The bilayer was formed by one of two
      methods: fusion of lamellar vesicles or by the combination of Langmuir-Blodgett
      (LB) and Langmuir-Schaefer (LS) deposition. Results indicate that phospholipid
      vesicles rapidly adsorb and fuse to form a film at the electrode surface. The
      resulting film undergoes a very slow structural transformation until a
      characteristic corrugated phase is formed. Force-distance curve measurements
      reveal that the thickness of the corrugated phase is consistent with the
      thickness of a bilayer lipid membrane. The formation of the corrugated phase may
      be explained by considering the elastic properties of the film and taking into
      account spontaneous curvature induced by the asymmetric environment of the
      bilayer, in which one side faces the gold substrate and the other side faces the
      solution. The effect of temperature and electrode potential on the stability of
      the corrugated phase has also been described.

PMID- 18712890
TI  - Mechanistic study of the synthesis of Au nanotadpoles, nanokites, and microplates
      by reducing aqueous HAuCl4 with poly(vinyl pyrrolidone).
AB  - This article describes a simple approach to anisotropic Au nanostructures with
      various shapes by reducing HAuCl 4 with poly(vinyl pyrrolidone) (PVP) in aqueous
      solutions without the use of any additional capping agent or reductant. In this
      approach, the commercially available PVP servers as a mild reducing agent thanks
      to its hydroxyl (-OH) end groups, enabling kinetic control over both nucleation
      and growth. As the volume of HAuCl 4 solution added to the reaction was
      increased, the morphology of Au nanostructures evolved from nanotadpoles to
      nanokites and then triangular and hexagonal microplates. The slow reduction rate
      associated with the mild reducing power of PVP plays a critical role in forming
      nanoplates during nucleation as well as their growth into highly anisotropic
      nanostructures. Electron microscopy studies reveal that the nanotadpoles and
      nanokites are formed through the linear fusion of small Au particles (<10 nm) to
      the initially formed nanoplates, whereas the microplates result from the
      continuous addition of Au atoms to the side faces of nanoplates. Through this
      morphological control, the localized surface plasmon resonance peaks of these Au
      nanostructures can be tuned in the visible and near-IR regions.

PMID- 18712891
TI  - Simulations of lipid adsorption on TiO2 surfaces in solution.
AB  - Molecular dynamics simulations are carried out to study the adsorption of three
      lipids, namely, DOPC, DOPS, and DMTAP, on TiO2(110) rutile surfaces and the
      influence of the interface on their conformational properties. Three types of
      rutile (110) surfaces, characterized by a different degree of hydroxylation (the
      neutral nonhydroxylated and hydroxylated surfaces and a partially hydroxylated
      surface with charge density corresponding to physiological pH) are investigated
      using force fields derived from ab initio calculations and experimental data. It
      is found that the stability of the adsorbate and the strength of the attachment
      are strictly connected with the nature of both the lipid and the surface. Direct
      coordination of the phosphate or carbonyl oxygens of the lipids with available
      titanium sites, observed in the case of partially or nonhydroxylated layers,
      determines stronger adsorption and, as a consequence, reduced dynamics. For a
      given hydration state of the surface, the adsorption strengths are in the order
      DOPS > DOPC >> DMTAP, in agreement with experimental data according to which the
      presence of DOPS units inside lipid bilayers favors stronger adsorption and lower
      mobility. The adsorption geometry, the hydration state of the lipid headgroups,
      and the dynamical processes (detachment, diffusion, etc.) occurring at the
      lipid/oxide interface are analyzed in detail, putting on a roughly quantitative
      basis time scales and energy barriers of the latter processes.

PMID- 18712892
TI  - Stretching a polymer brush by making in situ cyclodextrin inclusion complexes.
AB  - The interaction between poly(ethylene oxide) (PEO) chains grafted onto
      polystyrene latex particles and alpha-, beta-, and gamma-cyclodextrins (CD) was
      studied by small-angle neutron scattering. The particles were contrast-matched to
      the solvent in order that only the scattering from the polymer layers was
      detected. The signal from the layers was fitted to a double-exponential volume
      fraction profile. The effects of adding cyclodextrin on the polymer profile are
      shown as a function of cyclodextrin concentration. The polymer layers are seen to
      extend on addition of CD, which is consistent with a complexation between the
      grafted PEO and the CD molecules. The effect is the strongest with alpha-CD.

PMID- 18712893
TI  - Streaming potential generated by a long viscous drop in a capillary.
AB  - The streaming potential generated by motion of a long drop of viscosity mu(d) =
      lambdamu in a uniform circular capillary filled with fluid of viscosity mu is
      investigated by means of a model previously used to study electrophoresis of a
      charged mercury drop in water. The capillary wall is at potential zeta c relative
      to the bulk fluid within it, and the surface of the drop is at potential zeta(d).
      Potentials are assumed to be sufficiently small so that the charge cloud is
      described by the linearized Poisson-Boltzmann equation, and the Debye length
      characterizing the thickness of the charge cloud is assumed to be thin compared
      with the gap h(0) between the drop and the capillary wall. Ions in the external
      fluid are not allowed to discharge at the surface of the drop, and the wall of
      the capillary has a nonzero surface conductivity sigma c. The drop is assumed to
      be sufficiently long so that end effects can be neglected. Recirculation of fluid
      within the drop gives rise to an enhanced streaming current when zeta(d) is
      nonzero, leading to an anomalously high streaming potential. This vanishes as the
      drop viscosity becomes large. If V is the velocity of the drop and gamma is the
      coefficient of interfacial tension between the two fluids, then the capillary
      number is Ca = mu V/gamma, and the gap varies as h(0)planck'sCa(2/3). When Ca is
      small, the gap h(0) is small and electrical conduction along the narrow gap is
      dominated by the surface conductivity sigma(c) of the capillary wall, which is
      constant. The electrical current convected by flowing fluid is proportional to
      Ca, as is the change in streaming potential caused by the presence of the drop.
      If sigma(c) = 0, then the electrical conductance of the gap depends on its width
      h(0) and on the bulk fluid conductivity sigma and becomes small as h(0)
      approximately equal to Ca(2/3) --> 0. The streaming potential required to cancel
      the O(Ca) convection current therefore varies as Ca(1/3). If sigma(c) = 0 and the
      drop is rigid (lambda --> infinity), then the change in streaming potential over
      and above that expected due to the change in pressure gradient is proportional to
      the difference in potentials zeta(c)-zeta(d).

PMID- 18712894
TI  - Ultrasonic nebulization in aqueous solutions and the role of interfacial
      adsorption dynamics in surfactant enrichment.
AB  - High-density micron-sized aerosols from liquid surfaces were generated using an
      ultrasonic (frequency = 1056 kHz) nebulization technique in the absence and
      presence of a number of surfactants. The surfactants included cationic
      surfactants, cetylpyridinium chloride and dodecylpyridinium chloride, and anionic
      surfactants, sodium dodecylbenzenesulfonate and sodium benzenesulfonate. The
      nebulization process generated aerosols of a narrow size distribution with a
      number mean diameter of about 3.4 mum, which is close to the theoretical value
      suggested by the Lang Equation. The aerosol droplets are enriched in surfactant
      as a consequence of the large interfacial area. The enrichment factor varied for
      different surfactants, depending on their surface activity. The extent of
      enrichment can be related to the rate of mass transfer of surfactant to the
      liquid surface. Surface concentrations of between 15 and 30% of the equilibrium
      value are observed, indicating turbulent mass transfer is the rate limiting step.

PMID- 18712895
TI  - Molecular level investigation of organization in ternary lipid bilayer: a
      computational approach.
AB  - The differential organization of lipid components in a multicomponent membrane
      leads to formation of domains having diverse composition and size. Cholesterol
      and glycosphingolipids are known to be important components of such lateral
      assembly. We report here the ordering of cholesterol around ganglioside GM1 and
      the nature of the cluster from an all-atom simulation of a ternary lipid system.
      The results are compared with a binary bilayer and a pure phospholipid bilayer.
      The difference in molecular rearrangements in ternary and binary lipid mixture
      shows the role of GM1 in the rearrangement of cholesterol. Calculation of the
      radial distribution function, rotational reorientation, and residence time
      analysis of cholesterol shows that cholesterol is preferentially accumulating
      near gangliosides, while the lateral translational motion, rotational diffusion,
      and order parameter of phospholipids characterize the amount of rigidity imparted
      on the phospholipid bilayer.

PMID- 18712896
TI  - Probing ras effector interactions on nanoparticle supported lipid bilayers.
AB  - Many biological processes take place in close proximity to lipid membranes. For a
      detailed understanding of the underlying mechanisms, tools are needed for the
      quantitative characterization of such biomolecular interactions. In this work, we
      describe the development of methods addressing the dynamics and affinities of
      protein complexes attached to an artificial membrane system. A semisynthetic
      approach provides the Ras protein with palmitoyl anchors, which allow stable
      membrane insertion, as a paradigm for membrane associated proteins that interact
      with multiple effectors. An artificial membrane system is constituted by
      nanoparticles covered with a lipid bilayer. Such a stable suspension allows for
      the characterization of the interaction between membrane-bound Ras and effector
      proteins using conventional fluorescence-based methods.

PMID- 18712897
TI  - Characterization of and mechanism for copper-induced thioureation of serum
      albumin.
AB  - Thioureas (Tus) are widely used in chemical and pharmaceutical industries. This
      study demonstrated that copper induced the disulfide-linkage between Tus, such as
      alpha-naphthylthiourea (ANTU) and fluorescein-5-isothiocyanate cadaverine (FTC),
      with albumin (Alb), a major carrier protein in plasma with multiple functions.
      This reaction was absolutely copper-dependent, whereas cobalt, nickel, calcium,
      magnesium, zinc, iron, and manganese ions could not induce the same reaction. The
      reaction was substrate dose-dependent, and occurred optimally at pH 6.5. The
      resulting conjugated product was heat-labile, but stable in pH 6.0-8.0 buffer at
      25 degrees C. The linkage could be reduced by Cu(I) (in acidic pH) and thiol
      reducing agents. The mechanism of albumin thioureation was concluded: (i) the
      binding of Cu(II) with albumin is not necessary for the reaction, while the
      formation of Tus-Cu(II) complex is essential; (ii) thioureation resulted from the
      attack of Tus-Cu(II) at Alb-Cys(34)-SH to form the Alb-Cys(34)-S-S-Tus complex
      accompanied by the release of Cu(I); (iii) the released Cu(I) would back inhibit
      the reaction because of its competition with Cu(II) for Tus binding. These
      phenomenons may have important implications for the pharmacokinetics of thiourea
      based drugs in plasma.

PMID- 18712898
TI  - Bacterial RNase P RNA is a drug target for aminoglycoside-arginine conjugates.
AB  - The ribonuclease P (RNase P) holoenzymes are RNPs composed of RNase P RNA (PRNA)
      and a variable number of P protein subunits. Primary differences in structure and
      function between bacterial and eukaryotic RNase P and its indispensability for
      cell viability make the bacterial enzyme an attractive drug target. On the basis
      of our previous studies, aminoglycoside-arginine conjugates (AACs) bind to HIV-1
      TAR and Rev responsive element (RRE) RNAs significantly more efficiently than
      neomycin B. Their specific inhibition of bacterial rRNA as well as the findings
      that the hexa-arginine neomycin derivative (NeoR6) is 500-fold more potent than
      neomycin B in inhibiting bacterial RNase P, led us to explore the structure
      function relationships of AACs in comparison to a new set of aminoglycoside
      polyarginine conjugates (APACs). We here present predicted binding modes of AACs
      and APACs to PRNA. We used a multistep docking approach comprising rigid docking
      full scans and final refinement of the obtained complexes. Our docking results
      suggest three possible mechanisms of RNase P inhibition by AACs and APACs:
      competition with the P protein and pre-tRNA on binding to P1-P4 multihelix
      junction and to J19/4 region (probably including displacement of Mg2+ ions from
      the P4 helix) of PRNA; competition with Mg2+ ions near the P15 loop; and
      competition with the P protein and/or pre-tRNA near the P15 helix and interfering
      with interactions between the P protein and pre-tRNA at this region. The APACs
      revealed about 10-fold lower intermolecular energy than AACs, indicating stronger
      interactions of APACs than AACs with PRNA.

PMID- 18712899
TI  - Evaluation of the pharmacokinetic effects of various linking group using the
      111In-DOTA-X-BBN(7-14)NH2 structural paradigm in a prostate cancer model.
AB  - The high incidence of BB2 receptor (BB2r) expression in various cancers has
      prompted investigators to pursue the development of BB2r-targeted agents for
      diagnostic imaging, chemotherapy, and radiotherapy. Development of BB2r-targeted
      agents, based on the bombesin (BBN) peptide, has largely involved the use of the
      bifunctional chelate approach in which the linking group serves several key roles
      including pharmacokinetic modification. Understanding the in vivo properties of
      the various pharmacokinetic modifying linking groups is crucial for developing
      BB2r-targeted agents with improved targeting and clearance characteristics. The
      goal of this study was to systematically evaluate the pharmacokinetic profile of
      aliphatic hydrocarbon, aromatic, and poly(ethylene glycol) (ether) functional
      groups in order to obtain a better understanding of the in vivo properties of
      these pharmacokinetic modifiers. Specifically, we synthesized six radioconjugates
      with the structure 111In-DOTA- X-BBN(7-14)NH2, where X = 8-aminooctanoic acid (8
      AOC), 5-amino-3-oxapentyl-succinamic acid (5-ADS), 8-amino-3,6-dioxaoctyl
      succinamic acid (8-AOS), p-aminobenzoic acid (AMBA), Gly-AMBA, and Gly- p
      aminomethylbenzoic acid (Gly-AM2BA). All of the (nat)In-conjugates demonstrated
      nanomolar binding affinities to the BB2r. In CF-1 mice, the BB2r uptake in the
      pancreas of radioconjugates containing aromatic linking groups was found to be
      significantly higher at 1 h postinjection than the radioconjugates with ether
      linker moieties. For PC-3 tumor-bearing SCID mice, the tumor uptake was found to
      be 6.66 +/- 2.00, 6.21 +/- 1.57, 6.36 +/- 1.60, 4.46 +/- 0.81, and 7.76 +/- 1.19
      %ID/g for the 8-AOC, 8-ADS, AMBA, Gly-AMBA, and Gly-AM2BA radioconjugates,
      respectively, at 15 min postinjection. By 24 h postinjection, the radioconjugates
      containing aromatic groups exhibited the highest percentage tumor retention with
      11.4%, 19.8%, 26.6%, 25.8%, and 25.5% relative to the 15 min values remaining in
      the tumor tissue for the 8-AOC, 8-ADS, AMBA, Gly-AMBA, and Gly-AM2BA
      radioconjugates, respectively. Fused Micro-SPECT/CT imaging studies performed at
      24 h postinjection revealed substantial accumulation of radioactivity in the
      tumor tissue for all radioconjugates. In both biodistribution and Micro-SPECT/CT
      imaging studies, the radioconjugates containing aromatic linking groups typically
      exhibited significantly higher G.I. tract retention than the hydrocarbon or ether
      linking moieties. In conclusion, our studies indicate that radioconjugates
      incorporating aromatic linking groups, of the type investigated, generally
      demonstrated enhanced retention in BB2r expressing tissues in comparison to
      either the hydrocarbon or ether linking moieties. Furthermore, this investigation
      clearly demonstrates the significance of the linking group upon not only the in
      vivo clearance of the radiopharmaceutical, but also on the in vivo uptake and
      retention of the BB2r-targeted agent in tumor tissue. Future designs of BB2r
      targeted agents should include a careful consideration of the effect linking
      group functionality has upon tumor targeting and retention.

PMID- 18712900
TI  - closo-borane conjugated regulatory peptides retain high biological affinity:
      synthesis of closo-borane conjugated Tyr(3)-octreotate derivatives for BNCT.
AB  - Despite the improvements in cancer therapy during the past years, high-grade
      gliomas and many other types of cancer are still extremely resistant to current
      forms of therapy. Boron neutron capture therapy (BNCT) provides a promising way
      to destroy cancer cells without damaging healthy tissue. However, BNCT in
      practice is still limited due to the lack of boron-containing compounds that
      selectively deliver boron to cancer cells. Since many neuroendocrine tumors show
      an overexpression of the somatostatin receptor, it was our aim to synthesize
      compounds that contain a large number of boron atoms and still show high affinity
      toward this transmembrane receptor. The synthetic peptide Tyr (3)-octreotate
      (TATE) was chosen as a high-affinity and internalizing tumor targeting vector
      (TTV). Novel boron cluster compounds, containing 10 or 20 boron atoms, were
      coupled to the N-terminus of TATE. The obtained affinity data demonstrate that
      the use of a spacer between TATE and the closo-borane moiety is the option to
      avoid a loss of biological affinity of closo-borane conjugated TATE. For the
      first time, it was shown that closo-borane conjugated regulatory peptides retain
      high biological affinity and selectivity toward their transmembrane tumor
      receptors. The results obtained and the improvement of spacer and boron building
      block chemistry may stimulate new directions for BNCT.

PMID- 18712901
TI  - Changes in the Gallus gallus proteome induced by Marek's disease virus.
AB  - Marek's disease virus (MDV) is a highly oncogenic avian herpesvirus. We have used
      a modified MudPIT analysis to examine the effect of MDV infection on the chicken
      proteome. We identified 3561 unique nonphosphorylated peptides, representing 1460
      chicken proteins, in a mock-infected sample versus 4240 unique nonphosphorylated
      peptides, representing 1676 proteins, in an MDV-infected sample. Of these unique
      peptides, 59.1% from the mock- and 49.6% from the MDV-infected samples were
      detected in both samples, and for the represented proteins, 69.1% from the mock-
      and 60.2% from the MDV-infected samples were common to both samples. In terms of
      phosphorylation, 357 and 506 phosphopeptides, representing 342 and 483 proteins,
      were detected in the mock- and MDV-infected samples, respectively. At the
      phosphopeptide level, 10.1% from the mock- and 7.1% from the MDV-infected samples
      overlapped, and for the represented phosphoproteins, 12.0% from the mock- and
      8.5% from the MDV-infected samples were common to both samples. There were no
      significant differences in the hydropathicity values and number of transmembrane
      domains of the identified protein sets. Subtle differences were observed for
      subcellular localizations of the identified proteins. These results suggest that
      MDV infection may alter host cell biochemistry by perturbing the host's proteomic
      composition.

PMID- 18712902
TI  - Atomistic insights into the inhibition of cysteine proteases: first QM/MM
      calculations clarifying the stereoselectivity of epoxide-based inhibitors.
AB  - Due to their important role in many diseases, cysteine proteases represent new
      promising drug targets. An important class of cysteine-protease inhibitors is
      derived from the naturally occurring compound E64, possessing an epoxysuccinyl
      moiety as warhead. Experimental studies show stereoselectivity concerning the
      inhibition potency, e.g., a trans-configured epoxide ring is essential for
      inhibition, and furthermore, in most cases, the ( S, S)-configured inhibitors
      have a higher inhibition potency than their ( R, R)-counterparts. However, the
      underlying effects are not fully understood. In this work, such effects are
      investigated by classical molecular dynamics simulations and combined quantum
      mechanics/molecular modeling (QM/MM) calculations for the E64c-cathepsin B
      complex. Our computations reveal that the hydrogen bonding network between the
      enzyme and the E64c (or its derivatives) determines the stereoselectivity of the
      subsequent ring opening reaction by governing the distance between the attacking
      thiolate and the attacked C2 atom of the epoxide ring. For the ( S, S)
      configuration, a strong network can be realized which enables a close contact
      between the reacting centers, so that the irreversible step becomes very
      efficient. The ( R, S)-configuration ( cis-configuration) can only form networks
      in which the two reacting centers are so far away from each other that the
      irreversible step can hardly happen. The ( R, R)-configuration is in between,
      less optimal than the ( S, S)-configuration but much better than the ( R, S)
      configuration. Exceptions where the ( R, R)-configurations shows higher potency
      than the ( S, S) ones are also explained.

PMID- 18712903
TI  - Formation of a rotaxane from the end-capping process of a pseudorotaxane. Effects
      of the solvent.
AB  - The effects that the solvent exerts on the end-capping process of a
      pseudorotaxane formed by the [Ru(NH 3) 5(4,4'-bpy)]2+ complex and beta
      cyclodextrin were studied. In this process the 4,4'-bpy ligand acts as rigid axle
      and the cyclodextrin as ring or macrocycle. The stopper used was the [Fe(CN) 5
      H2O]3(-) complex. The solvents used were mixtures of ethyleneglycol-water and
      tert-butyl alcohol-water. Results showed similar, although strange, behavior in
      both media studied. Thus, a decrease of the observed rate constant was obtained
      when the concentration of cyclodextrin increases for all the media studied.
      However, at fixed cyclodextrin concentrations, an increase of k obs was obtained
      when small quantities of the cosolvent were added to the medium and, further, a
      decrease of k obs for the higher quantities of the organic solvents. This strange
      behavior could be explained by taking into account electrostatic and specific
      solvent (solvent-solvent and solvent-solute) effects.

PMID- 18712904
TI  - Spectral characteristics of polyaniline nanostructures synthesized by using
      cyclic voltammetry at different scan rates.
AB  - The polyaniline nanofibers with different sizes were synthesized by using cyclic
      voltammetry at different potential scan rates, in the presence of
      ferrocenesulfonic acid. The potential scan rate controlled the formation and
      growth of polyaniline nuclei, which plays a key role in controlling nanofiber
      sizes. The average diameters of nanofibers decreased from about 130 nm to about
      80 nm as the potential scan rate increased from 6 to 60 mV s (-1). We first
      observed an ordered change in the following spectra with the nanofiber sizes of
      polyaniline. The spectra of the X-ray diffraction indicated that the partially
      crystalline form existed in the polyaniline nanofibers and that the crystallinity
      of polyaniline increased with decreasing diameter of polyaniline nanofibers. The
      ESR spectra revealed the fact that the decrease in the intensity of the ESR
      signal was accompanied by the increase in the value of the peak-to-peak line
      width Delta H pp as the diameter of polyaniline nanofibers decreased. The 1H NMR
      spectra showed that a peak in a triplet caused by the +/- NH free radical was
      split into two peaks with different intensities and that their relative intensity
      also changed with the diameter of the polyaniline nanofibers.

PMID- 18712905
TI  - Transmission electron microscopy study of solvent-induced phase morphologies of
      environmentally responsive mixed homopolymer brushes on silica particles.
AB  - We report in this work a transmission electron microscopy study of phase
      morphologies of environmentally responsive mixed poly( t-butyl acrylate) (P
      tBA)/polystyrene (PS) brushes and mixed poly(acrylic acid) (PAA)/PS brushes on
      180 nm silica particles after treatments with nonselective good solvents and
      selective solvents, respectively. Mixed P tBA/PS brushes were grown from Y
      initiator-functionalized silica particles by sequential atom transfer radical
      polymerization and nitroxide-mediated radical polymerization. Mixed PAA/PS
      brushes were prepared from mixed P tBA/PS brushes by removal of the t-butyl
      groups. For mixed P tBA/PS brushes with P tBA M n of 24.2 kDa and PS M n of 23.0
      kDa and the corresponding mixed PAA/PS brushes, random worm-like, nearly
      bicontinuous nanostructures were formed from lateral microphase separation when
      the particles were cast from nonselective good solvents (chloroform for mixed P
      tBA/PS brushes and N, N-dimethylformamide for mixed PAA/PS brushes). The feature
      sizes were on the order of polymer chain root-mean-square end-to-end distances (
      approximately 10 nm). In contrast, mixed P tBA/PS brushes with lower molecular
      weights (P tBA M n = 10.4 kDa and PS M n = 11.9 kDa) did not strongly phase
      separate after being cast from chloroform. After the solvents in the particle
      dispersions were gradually changed to selective solvents ( n-octane for mixed P
      tBA/PS brushes and H2O for mixed PAA/PS brushes), isolated microdomains with an
      average size of 14-19 nm were formed as one grafted polymer collapsed and
      associated to form isolated microdomains, which were shielded by another grafted
      polymer yielding surface-tethered micellar structures. These results confirmed
      the theoretical predictions of the formation of "rippled" nanostructures and
      surface micellar structures of mixed homopolymer brushes induced by nonselective
      and selective solvents, respectively.

PMID- 18712906
TI  - Resonance energy transfer in the solution phase photophysics of -Re(CO)3 L+
      pendants bonded to poly(4-vinylpyridine).
AB  - Polymers with general formula ([(vpy) 2vpyRe(CO) 3(tmphen) (+)]) n ([(vpy)
      2vpyRe(CO) 3(NO 2-phen) (+)]) m (NO 2-phen = 5-nitro-1,10-phenanthroline; tmphen
      = 3,4,7,8-tetramethyl-1,10-phenanthroline); vpy = 4-vinylpyridine) were prepared
      and their morphologies were studied by transmission electron microscopy (TEM).
      Multiple morphologies of aggregates from these Re I polymers were obtained by
      using different solvents. Energy transfer between MLCT Re-->tmphen and MLCT Re-
      >NO 2 -phen excited states inside the polymers was evidenced by steady state and
      time-resolved spectroscopy. Current Forster resonance energy transfer theory was
      successfully applied to energy transfer processes in these polymers.

PMID- 18712907
TI  - Molecular packing effects on the optical spectra and triplet dynamics in
      oligofluorene films.
AB  - We report on the triplet spectra and dynamics in two types of oligomeric films
      deposited by two different techniques: thermal evaporation and spin coating. The
      different molecular arrangement in both films is manifested in a red shift of the
      absorption, PL, and T1-Tn absorption spectra of the sublimated film relative to
      the spin-coated one. Triplet recombination dynamics studied with steady-state
      photoinduced absorption (PA) spectroscopy follow a dispersive bimolecular
      recombination model away from the trap filling regime. We obtained values for the
      triplet bimolecular recombination ratio (beta) of 3.4 x 10 (-14) and 1.1 x 10 (
      15) cm3 s (-1) for evaporated and spin-coated film, respectively, the difference
      being attributed to diverse molecular arrangement in both films.

PMID- 18712909
TI  - Permittivity-dependent entropy driven complexation ability of cone and paco
      tetranitro-calix[4]arene toward para-substituted phenols.
AB  - Considering the importance of the polarizability of the rings of calixarenes in
      the entropy-driven interaction processes, we examined the effect of entropy
      compensation on the complex formation of cone and partial cone (paco) conformers
      of tetranitro-calix [4]arene, possessing O-ethyl substituents at the lower rim.
      Both calixarene conformers were fully characterized including X-ray
      crystallography. Various para-substituted phenols were used as guest molecules.
      Photoluminescence (PL) measurements and quantum-chemical (QC) investigations were
      used. A permittivity dependence of the molecular interactions was obtained in
      different alcohols as solvents. It was found that the cone conformer of the title
      calixarene derivative forms stable complexes with all phenols of the p
      substituted series. The free enthalpy changes show very high complex stability of
      cone calixarene with p-nitro and p-chloro-substituted phenols. In the cases of
      parent phenol, p-cresol and p- tBu-phenol, the stability is significantly lower;
      however, it slightly increases with the increasing electron density on the
      aromatic ring of guest molecules. Similarly, the entropy changes are
      significantly different for these two separated groups: the entropy changes
      obtained in the former cases are nearly the same, while large differences in the
      formation entropy were obtained in the latter cases. Both the experimental and
      theoretical investigations revealed that no considerable interaction exists
      between phenols and the paco conformer of the title calixarene. It is probably
      due to the locking of the calixarene cavity by the bent O-ethyl chain.

PMID- 18712910
TI  - Metal ion reactive thin films using spray electrostatic LbL assembly.
AB  - By using the spray-layer-by-layer (Spray-LbL) technique, the number of metal
      counterions trapped within LbL coatings is significantly increased by kinetically
      freezing the film short of equilibrium, potentially limiting interchain
      penetration and forcing chains to remain extrinsically compensated to a much
      greater degree than observed in the traditional dipped LbL technique. The basis
      for the enhanced entrapment of metal ions such as Cu2+, Fe2+, and Ag+ is
      addressed, including the equilibrium driving force for extrinsic compensation by
      soft versus hard metal ions and the impact of Spray-LbL on the kinetics of
      polymer-ion complexation. These polymer-bound metal-ion coatings are also
      demonstrated to be effective treatments for air filtration, functionalizing
      existing filters with the ability to strongly bind toxic industrial compounds
      such as ammonia or cyanide gases, as well as chemical warfare agent simulants
      such as chloroethyl ethyl sulfide. On the basis of results reported here, future
      work could extend this method to include other toxic soft-base ligands such as
      carbon monoxide, benzene, or organophosphate nerve agents.

PMID- 18712908
TI  - Electrostatic properties of aqueous salt solution interfaces: a comparison of
      polarizable and nonpolarizable ion models.
AB  - The effects of ion force field polarizability on the interfacial electrostatic
      properties of approximately 1 M aqueous solutions of NaCl, CsCl, and NaI are
      investigated using molecular dynamics simulations employing both nonpolarizable
      and Drude-polarizable ion sets. Differences in computed depth-dependent
      orientational distributions, "permanent" and induced dipole and quadrupole moment
      profiles, and interfacial potentials are obtained for both ion sets to further
      elucidate how ion polarizability affects interfacial electrostatic properties
      among the various salts relative to pure water. We observe that the orientations
      and induced dipoles of water molecules are more strongly perturbed in the
      presence of polarizable ions via a stronger ionic double layer effect arising
      from greater charge separation. Both anions and cations exhibit enhanced induced
      dipole moments and strong z alignment in the vicinity of the Gibbs dividing
      surface (GDS) with the magnitude of the anion induced dipoles being nearly an
      order of magnitude larger than those of the cations and directed into the vapor
      phase. Depth-dependent profiles for the trace and z z components of the water
      molecular quadrupole moment tensors reveal 40% larger quadrupole moments in the
      bulk phase relative to the vapor which mimics a similar observed 40% increase in
      the average water dipole moment. Across the GDS, the water molecular quadrupole
      moments increase nonmonotonically (in contrast to the water dipoles) and exhibit
      a locally reduced contribution just below the surface due to both orientational
      and polarization effects. Computed interfacial potentials for the nonpolarizable
      salts yield values 20-60 mV more positive than pure water and increase by an
      additional 30-100 mV when ion polarizability is included. A rigorous
      decomposition of the total interfacial potential into ion monopole, water and ion
      dipole, and water quadrupole components reveals that a very strong, positive ion
      monopole contribution is offset by negative contributions from all other
      potential sources. Water quadrupole components modulated by the water density
      contribute significantly to the observed interfacial potential increments and
      almost entirely explain observed differences in the interfacial potentials for
      the two chloride salts. By lumping all remaining nonquadrupole interfacial
      potential contributions into a single "effective" dipole potential, we observe
      that the ratio of quadrupole to "effective" dipole contributions range from 2:1
      in CsCl to 1:1.5 in NaI, suggesting that both contributions are comparably
      important in determining the interfacial potential increments. We also find that
      oscillations in the quadrupole potential in the double layer region are opposite
      in sign and partially cancel those of the "effective" dipole potential.

PMID- 18712911
TI  - Oxygen-17 nuclear magnetic resonance study of the structure of mixed cation
      calcium-sodium silicate glasses at high pressure: implications for molecular link
      to element partitioning between silicate liquids and crystals.
AB  - The structure of silicate glasses and the corresponding liquids at high pressure
      and their structure-property relations remain difficult questions in modern
      physical chemistry, geochemistry, and condensed matter physics. Here we report
      high- resolution solid-state O-17 3QMAS NMR spectra for mixed cation Ca-Na
      silicate glasses quenched from melts at high pressure up to 8 GPa. The spectra
      provide the experimental evidence for the varying pressure-dependence in two
      different types of nonbridging oxygen (NBO) environments (i.e., Na-O-Si and mixed
      (Ca,Na)-O-Si) in the single glass composition. The percentage of NBO drops
      significantly with increasing pressure and is a complex function of melt
      composition, including cation field strength of network modifying cations. A
      decrease in NBO fraction with pressure is negatively correlated with the element
      partitioning coefficient between crystals and liquids at high pressure.

PMID- 18712912
TI  - Molecular dynamics simulations of cardiolipin bilayers.
AB  - Cardiolipin is a key lipid component in the inner mitochondrial membrane, where
      the lipid is involved in energy production, cristae structure, and mechanisms in
      the apoptotic pathway. In this article we used molecular dynamics computer
      simulations to investigate cardiolipin and its effect on the structure of lipid
      bilayers. Three cardiolipin/POPC bilayers with different lipid compositions were
      simulated: 100, 9.2, and 0% cardiolipin. We found strong association of sodium
      counterions to the carbonyl groups of both lipid types, leaving in the case of
      9.2% cardiolipin virtually no ions in the aqueous compartment. Although binding
      occurred primarily at the carbonyl position, there was a preference to bind to
      the carbonyl groups of cardiolipin. Ion binding and the small headgroup of
      cardiolipin gave a strong ordering of the hydrocarbon chains. We found
      significant effects in the water dipole orientation and water dipole potential
      which can compensate for the electrostatic repulsion that otherwise should force
      charged lipids apart. Several parameters relevant for the molecular structure of
      cardiolipin were calculated and compared with results from analyses of coarse
      grained simulations and available X-ray structural data.

PMID- 18712914
TI  - Comparisons of multilayer H2O adsorption onto the (110) surfaces of alpha-TiO2
      and SnO2 as calculated with density functional theory.
AB  - Mono- and bilayer adsorption of H2O molecules on TiO2 and SnO 2 (110) surfaces
      has been investigated using static planewave density functional theory (PW DFT)
      simulations. Potential energies and structures were calculated for the
      associative, mixed, and dissociative adsorption states. The DOS of the bare and
      hydrated surfaces has been used for the analysis of the difference between the
      H2O interaction with TiO2 and SnO 2 surfaces. The important role of the bridging
      oxygen in the H2O dissociation process is discussed. The influence of the second
      layer of H2O molecules on relaxation of the surface atoms was estimated.

PMID- 18712913
TI  - UV resonance raman investigation of electronic transitions in alpha-helical and
      polyproline II-like conformations.
AB  - UV resonance Raman (UVRR) excitation profiles and Raman depolarization ratios
      were measured for a 21-residue predominantly alanine peptide, AAAAA(AAARA) 3A
      (AP), excited between 194 and 218 nm. Excitation within the pi-->pi* electronic
      transitions of the amide group results in UVRR spectra dominated by amide
      vibrations. The Raman cross sections and excitation profiles provide information
      about the nature of the electronic transitions of the alpha-helix and polyproline
      II (PPII)-like peptide conformations. AP is known to be predominantly alpha
      helical at low temperatures and to take on a PPII helix-like conformation at high
      temperatures. The PPII-like and alpha-helix conformations show distinctly
      different Raman excitation profiles. The PPII-like conformation cross sections
      are approximately twice those of the alpha-helix. This is due to hypochromism
      that results from excitonic interactions between the NV 1 transition of one amide
      group with higher energy electronic transitions of other amide groups, which
      decreases the alpha-helical NV 1 (pi-->pi*) oscillator strengths. Excitation
      profiles of the alpha-helix and PPII-like conformations indicate that the highest
      signal-to-noise Raman spectra of alpha-helix and PPII-like conformations are
      obtained at excitation wavelengths of 194 and 198 nm, respectively. We also see
      evidence of at least two electronic transitions underlying the Raman excitation
      profiles of both the alpha-helical and the PPII-like conformations. In addition
      to the well-known approximately 190 nm pi-->pi* transitions, the Raman excitation
      profiles and Raman depolarization ratio measurements show features between 205
      207 nm, which in the alpha-helix likely results from the parallel excitonic
      component. The PPII-like helix appears to also undergo excitonic splitting of its
      pi-->pi* transition which leads to a 207 nm feature.

PMID- 18712915
TI  - Combined atomistic simulation and quasielastic neutron scattering study of the
      low-temperature dynamics of hydrogen and deuterium confined in NaX zeolite.
AB  - A direct comparison of quasielastic neutron scattering experimental measurements
      and molecular dynamics computer simulations is carried out for the first time for
      hydrogen and deuterium confined in the nanostructure of faujasite type zeolites
      at a temperature of 100 K, in order to investigate the dependence of sorption
      thermodynamics and sorbate dynamics on the sorbed phase concentration. The
      charged crystal framework of NaX is digitally reconstructed based on X-ray
      diffraction spectra, with the compensating Na + positions determined by neutron
      diffraction data. For the quantum statistical mechanical description of the guest
      guest and guest-zeolite interactions, the temperature-dependent effective
      potential of Feynman and Hibbs is employed, resulting from an approximation to
      the quantum mechanical path integral formulation of the motion. Computer
      simulation and neutron scattering are found in satisfactory agreement, both
      exhibiting a slight increase of the self-diffusivity and a maximum in the
      transport diffusivity as a function of sorbate loading. Our findings are further
      elaborated on the basis of the quasichemical mean field theory in conjunction
      with a model for surface transport due to Reed and Ehrlich, through which the
      computed and measured dynamical behavior can be related to the strength of
      interactions between the sorbate molecules.

PMID- 18712916
TI  - Molecular state and distribution of fullerenes entrapped in sol-gel samples.
AB  - A novel synthetic method that can encapsulate fullerene molecules (pure C60, pure
      C70, or their mixture) over a wide range of concentrations ranging from
      micromolar to millimolar in hybrid glass by a sol-gel method without any time
      consuming, complicated, and unwanted extra steps (e.g., addition of a surfactant
      or derivatization of the fullerenes) has been successfully developed. The
      molecular state and distribution of encapsulated fullerene molecules in these sol
      gel samples were unequivocally characterized using newly developed multispectral
      imaging techniques. The high sensitivity (single-pixel resolution) and ability of
      these instruments to record multispectral images at different spatial resolutions
      (approximately 10 microm with the macroscopic instrument and approximately 0.8
      microm with the microscopic instrument) make them uniquely suited for this task.
      Specifically, the imaging instruments can be used to simultaneously measure
      multispectral images of sol-gel-encapsulated C60 and C70 molecules at many
      different positions within a sol-gel sample in an area either as large as 3 mm x
      4 mm (with the macroscopic imaging instrument) or as small as 0.8 microm x 0.8
      microm (with the microscopic instrument). The absorption spectrum of the
      fullerene molecule at each position can then be calculated either by averaging
      the intensity of a 15 x 15 square of pixels (which corresponds to an area of 3 mm
      x 4 mm) or from the intensity of a single pixel (i.e., an area of about 0.8
      microm x 0.8 microm), respectively. The molecular state and distribution of
      fullerene molecules within sol-gel samples can then be determined from the
      calculated spectra. It was found that spectra of encapsulated C60 and C70
      measured at five different positions within a sol-gel sample were similar not
      only to one another but also to spectra measured at six different times during
      the sol-gel reaction process (from t = 0 to 10 days). Furthermore, these spectra
      are similar to the corresponding spectra of monomeric C60 or C70 molecules in
      solution. Similarly, spectra of sol-gel samples containing a mixture of C60 and
      C70 were found to be the same at five different positions, as well as similar to
      spectra calculated from an average of the spectra of C60 and C70 either
      encapsulated in a sol-gel or in solution. It is evident from these results that
      C60 and C70 molecules do not undergo aggregation upon encapsulation into a sol
      gel but rather remain in their monomeric state. Furthermore, entrapped C60 and
      C70 molecules in their monomeric state were distributed homogeneously throughout
      the entire sol-gel samples. Such a conclusion can be readily, quickly, and easily
      obtained, not with traditional spectroscopic techniques based on the use of a
      single-channel detector (absorption, fluorescence, infrared, Raman) but rather
      with the newly developed multispectral imaging technique. More importantly, the
      novel synthetic method reported here makes it possible, for the first time, to
      homogenously entrap monomeric fullerene molecules (C60, C70, or their mixture) in
      a sol-gel at various concentrations ranging from as low as 2.2 mM C60 (or 190
      microM C70) to as high as 4.2 mM C60 (or 360 microM C70).

PMID- 18712917
TI  - Optimization of enzymatic biochemical logic for noise reduction and scalability:
      how many biocomputing gates can be interconnected in a circuit?
AB  - We report an experimental evaluation of the "input-output surface" for a
      biochemical AND gate. The obtained data are modeled within the rate-equation
      approach, with the aim to map out the gate function and cast it in the language
      of logic variables appropriate for analysis of Boolean logic for scalability. In
      order to minimize "analog" noise, we consider a theoretical approach for
      determining an optimal set for the process parameters to minimize "analog" noise
      amplification for gate concatenation. We establish that under optimized
      conditions, presently studied biochemical gates can be concatenated for up to
      order 10 processing steps. Beyond that, new paradigms for avoiding noise buildup
      will have to be developed. We offer a general discussion of the ideas and
      possible future challenges for both experimental and theoretical research for
      advancing scalable biochemical computing.

PMID- 18712918
TI  - Light- and pH-dependent conformational changes in protein structure induce strong
      bending of purple membranes--active membranes studied by cryo-SEM.
AB  - Bacteriorhodopsin (BR) undergoes a conformational change during the photocycle
      and the proton transport through the membrane. For the first time, we could
      demonstrate by direct imaging of freely suspended native purple membranes (PMs)
      that the flat disk-like shape of PMs changes dramatically as soon as most of the
      BRs are in a state characterized by a deprotonated Schiff base. Light-induced
      shape changes are easily observed with mutated BRs of the BR-D96N type, i.e., all
      variants which show an increased M 2 lifetime. On the other hand, large-scale
      shape changes are induced by pH changes with PM containing mutated BRs of the BR
      D85T type, where Asp85 is replaced for a neutral amino acid. In such PMs, all BRs
      are titrated simultaneously and the resulting shape of the membranes depends on
      the initial shape only. As the majority of PMs in the "flat" state are more or
      less round disks, the bent membranes often comprise bowl-like and tube-like bent
      structures. The method presented here enables one to derive size changes of
      membrane-embedded BRs on the single molecule level from "macroscopic", easily
      accessible data like the curvature radii observed in cryo-SEM. The potential of
      BR as a pH-controlled and/or light-controlled microscaled biological actuator
      needs further consideration.

PMID- 18712919
TI  - Edelfosine is incorporated into rafts and alters their organization.
AB  - The effect of edelfosine (1- O-octadecyl-2- O-methyl-rac-glycero-3-phosphocholine
      or ET-18-OCH3) on model membranes containing 1-palmitoyl-2-oleoyl- sn-glycero-3
      phosphocholine/sphingomyelin/cholesterol (POPC/SM/cholesterol) was studied by
      several physical techniques. The sample POPC/SM (1:1 molar ratio) showed a broad
      phase transition as seen by DSC, X-ray diffraction, and 2H NMR. The addition of
      edelfosine to this sample produced isotropic structures at temperatures above the
      phase transition, as seen by 2H NMR and by 31P NMR. When cholesterol was added to
      give a POPC/SM/cholesterol (at a molar ratio 1:1:1), no transition was observed
      by DSC nor X-ray diffraction, and 2H NMR indicated the presence of a liquid
      ordered phase. The addition of 10 mol % edelfosine increased the thickness of the
      membrane as seen by X-ray diffraction and led to bigger differences in the values
      of the molecular order of the membrane detected at high and low temperatures, as
      detected through the M 1 first spectral moment from 2H NMR. These differences
      were even greater when 20 mol % edelfosine was added, and a transition was now
      clearly visible by DSC. In addition, a gel phase was clearly indicated by X-ray
      diffraction at low temperatures. The same technique pointed to greater membrane
      thickness in this mixture and to the appearance of a second membrane structure,
      indicating the formation of two separated phases in the presence of edelfosine.
      All of these data strongly suggest that edelfosine associating with cholesterol
      alter the phase status present in a POPC/SM/cholesterol (1:1:1 molar ratio)
      mixture, which is reputed to be a model of a raft structure. However, cell
      experiments showed that edelfosine colocalizes in vivo with rafts and that it may
      reach concentrations higher than 20 mol % of total lipid, indicating that the
      concentrations used in the biophysical experiments were within what can be
      expected in a cell membrane. The conclusion is that molecular ways of action of
      edelfosine in cells may involve the modification of the structure of rafts.

PMID- 18712920
TI  - Single-walled carbon nanotube as a unique scaffold for the multivalent display of
      sugars.
AB  - Single-walled carbon nanotube (SWNT) is a pseudo-one-dimensional nanostructure
      capable of carrying/displaying a large number of bioactive molecules and species
      in aqueous solution. In this work, a series of dendritic beta-D
      galactopyranosides and alpha-D-mannopyranosides with a terminal amino group were
      synthesized and used for the functionalization of SWNTs, which targeted the
      defect-derived carboxylic acid moieties on the nanotube surface. The higher-order
      sugar dendrons were more effective in the solubilization of SWNTs, with the
      corresponding functionalized nanotube samples of improved aqueous solubility
      characteristics. Through the functionalization, the nanotube apparently serves as
      a unique scaffold for displaying multiple copies of the sugar molecules in pairs
      or quartets. Results on the synthesis and characterization of these sugar
      functionalized SWNTs and their biological evaluations in binding assays with
      pathogenic Escherichia coli and with Bacillus subtilis (a nonvirulent simulant
      for Bacillus anthracis or anthrax) spores are presented and discussed.

PMID- 18712922
TI  - Coniferyl ferulate incorporation into lignin enhances the alkaline
      delignification and enzymatic degradation of cell walls.
AB  - Incorporating ester interunit linkages into lignin could facilitate fiber
      delignification and utilization. In model studies with maize cell walls, we
      examined how partial substitution of coniferyl alcohol (a normal monolignol) with
      coniferyl ferulate (an ester conjugate from lignan biosynthesis) alters the
      formation and alkaline extractability of lignin and the enzymatic hydrolysis of
      structural polysaccharides. Coniferyl ferulate moderately reduced lignification
      and cell-wall ferulate copolymerization with monolignols. Incorporation of
      coniferyl ferulate increased lignin extractability by up to 2-fold in aqueous
      NaOH, providing an avenue for producing fiber with less noncellulosic and lignin
      contamination or of delignifying at lower temperatures. Cell walls lignified with
      coniferyl ferulate were more readily hydrolyzed with fibrolytic enzymes, both
      with and without alkaline pretreatment. Based on our results, bioengineering of
      plants to incorporate coniferyl ferulate into lignin should enhance
      lignocellulosic biomass saccharification and particularly pulping for paper
      production.

PMID- 18712921
TI  - Self-assembling peptide-polymer hydrogels designed from the coiled coil region of
      fibrin.
AB  - Biomaterials constructed from self-assembling peptides, peptide derivatives, and
      peptide-polymer conjugates are receiving increasing attention as defined matrices
      for tissue engineering, controlled therapeutic release, and in vitro cell
      expansion, but many are constructed from peptide structures not typically found
      in the human extracellular matrix. Here we report a self-assembling biomaterial
      constructed from a designed peptide inspired by the coiled coil domain of human
      fibrin, the major protein constituent of blood clots and the provisional scaffold
      of wound healing. Targeted substitutions were made in the residues forming the
      interface between coiled coil strands for a 37-amino acid peptide from human
      fibrinogen to stabilize the coiled coil peptide bundle, while the solvent-exposed
      residues were left unchanged to provide a surface similar to that of the native
      protein. This peptide, which self-assembled into coiled coil dimers and
      tetramers, was then used to produce triblock peptide-PEG-peptide bioconjugates
      that self-assembled into viscoelastic hydrogel biomaterials.

PMID- 18712923
TI  - Investigations of glycosylation reactions with 2-N-acetyl-2N,3O-oxazolidinone
      protected glucosamine donors.
AB  - NIS/AgOTf-promoted glycosylations with ethyl 2,3-N,O-carbonyl-2-deoxy-1-thio-beta
      D-glucopyranoside donors can be performed with either alpha- or beta-selectivity
      by tuning the reaction conditions. Small amounts of AgOTf (0.1 equiv) and short
      reaction times give beta-selectivity, whereas 0.4 equiv of AgOTf and prolonged
      reaction times afford alpha-linked products. NMR-monitored glycosylation and
      anomerization experiments show initial formation of exclusively the beta-linkage,
      which anomerizes, through an intramolecular mechanism involving an endocyclic C-O
      bond cleavage, to the alpha-linkage.

PMID- 18712924
TI  - Palladium-catalyzed carbon-sulfur cross-coupling reactions with indium
      tri(organothiolate) and its application to sequential one-pot processes.
AB  - It was found that indium tri(organothiolate) is an effective nucleophilic
      coupling partner in Pd-catalyzed C-S cross-coupling reactions to produce the
      functionalized sulfides in excellent yields with high atom efficiency and
      complete regio- and chemoselectivity. The present method was efficiently applied
      to the sequential one-pot processes composed of selective double C-S cross
      coupling reactions and addition of allylindium or allenylindium to aldedyde to
      give the functionalized sulfides and bis(sulfides).

PMID- 18712925
TI  - Calix[6]tris(thio)ureas: heteroditopic receptors for the cooperative binding of
      organic ion pairs.
AB  - The straightforward syntheses of C3v symmetrical calix[6]trisureas and -thiourea
      have been achieved. NMR studies have shown that these flexible compounds possess
      a major cone conformation. While these neutral hosts can strongly bind anions
      such as AcO(-) or HSO4(-) through induced fit processes, they can also behave as
      unique heteroditopic receptors for organic ion pairs with a remarkable positive
      cooperativity in the complexation process, the anion acting as an allosteric
      effector.

PMID- 18712926
TI  - Reactivity of (2-alkenyl-3-pentene-1,5-diyl)iron complexes: preparation of
      functionalized vinylcyclopropanes and cycloheptadienes.
AB  - The reactivity of (2-alkenyl-3-pentene-1,5-diyl)iron complexes toward olefin
      metathesis, cycloaddition, and mild oxidations (MnO 2 or mCPBA) was examined.
      Cycloaddition reactions were observed to occur with modest diastereoselectivity
      (33-63% de). Decomplexation of the (3-pentenediyl) ligand may be accomplished by
      oxidation with either CAN or alkaline hydrogen peroxide to afford
      vinylcyclopropanecarboxylates or divinylcyclopropanecarboxylates. Reduction of
      the latter, followed by Cope rearrangement generates cycloheptadienylmethanols.
      These studies demonstrate that (2-alkenyl-3-pentene-1,5-diyl)iron complexes can
      serve as organometallic scaffolds for the preparation of a wide variety of
      structural motifs containing up to 5 contiguous stereocenters.

PMID- 18712927
TI  - Synthesis of unsymmetrical benzil licoagrodione.
AB  - A synthesis of unsymmetrical 1,2-diarylethane-1,2-dione is reported involving the
      intramolecular cyclization of anionic benzylic ester of the aryl benzyl ether
      followed by oxidation employing dioxirane. With the use of microwave irradiation,
      licoagrodione was prepared from Claisen rearrangement of the corresponding allyl
      phenyl ether 1,2-diketone readily available from the Lindlar's reduction of the
      corresponding alkyne derivative. Subsequent removal of protecting groups then
      furnished the desired product.

PMID- 18712928
TI  - Theoretical evidence for the nucleophilic addition of sulfur dioxide to 1,2
      bridged chloronium and bromonium ions.
AB  - The nucleophilic addition of SO2, SO2ClF, and SO2F2 to carbenium ions and the
      nucleophilic addition of SO2 to 1,2-bridged halonium ions are theoretically
      investigated by using B3LYP/6-311+G(d,p). On the basis of geometric changes in
      ion-solvent complexes compared to isolated molecules, the theoretical data for
      the addition of solvent to carbenium ions uniformly agree with experiments by
      Olah and Donovan. The relative reactivity of carbenium ions (methyl > ethyl > iso
      propyl > tert-butyl) follows the familiar trend based on electron demand at the
      carbenium center. The theoretical data for the addition of SO2 to 1,2-bridged
      halonium ions with use of similar methods indicate that this addition exhibits a
      reversed trend on the basis of the electron demand; SO2 adds to 2,2
      dimethylethylene chloronium and bromonium ions but does not add to the fluoronium
      analogue. Furthermore, the addition depends on the stereochemistry of the
      approaching SO2. When SO2 approaches syn to the halogen atom on the halonium ion,
      addition is observed. When SO2 is anti, addition is not observed. The reversed
      reactivity and stereochemistry of the addition of SO2 to halonium ions can be
      explained by electron donation from the halogen atom to the sulfur atom of the
      approaching SO2. This sulfur-halogen interaction activates the nucleophilicity of
      the approaching SO2 and makes a normally unreactive tertiary carbenium carbon
      susceptible to addition. The theoretical evidence for covalently bound halonium
      ion-SO2 complexes is discussed in the context of previously reported experimental
      evidence for the existence of equilibria involving beta-halocarbenium ions.

PMID- 18712929
TI  - Palladium-catalyzed one-step synthesis of isoindole-1,3-diones by carbonylative
      cyclization of o-halobenzoates and primary amines.
AB  - The palladium-catalyzed aminocarbonylation of o-halobenzoates produces 2
      substituted isoindole-1,3-diones in good yields. This methodology provides a good
      one-step approach to this important class of heterocycles and tolerates a variety
      of functional groups, including methoxy, alcohol, ketone, and nitro groups.

PMID- 18712930
TI  - Targeted tumor cell internalization and imaging of multifunctional quantum dot
      conjugated immunoliposomes in vitro and in vivo.
AB  - Targeted drug delivery systems that combine imaging and therapeutic modalities in
      a single macromolecular construct may offer advantages in the development and
      application of nanomedicines. To incorporate the unique optical properties of
      luminescent quantum dots (QDs) into immunoliposomes for cancer diagnosis and
      treatment, we describe the synthesis, biophysical characterization, tumor cell
      selective internalization, and anticancer drug delivery of QD-conjugated
      immunoliposome-based nanoparticles (QD-ILs). Pharmacokinetic properties and in
      vivo imaging capability of QD-ILs were also investigated. Freeze-fracture
      electron microscopy was used to visualize naked QDs, liposome controls,
      nontargeted QD-conjugated liposomes (QD-Ls), and QD-ILs. QD-ILs prepared by
      insertion of anti-HER2 scFv exhibited efficient receptor-mediated endocytosis in
      HER2-overexpressing SK-BR-3 and MCF-7/HER2 cells but not in control MCF-7 cells
      as analyzed by flow cytometry and confocal microscopy. In contrast, nontargeted
      QD-Ls showed minimal binding and uptake in these cells. Doxorubicin-loaded QD-ILs
      showed efficient anticancer activity, while no cytotoxicity was observed for QD
      ILs without chemotherapeutic payload. In athymic mice, QD-ILs significantly
      prolonged circulation of QDs, exhibiting a plasma terminal half-life ( t 1/2) of
      approximately 2.9 h as compared to free QDs with t 1/2 < 10 min. In MCF-7/HER2
      xenograft models, localization of QD-ILs at tumor sites was confirmed by in vivo
      fluorescence imaging.

PMID- 18712931
TI  - Coupled electrooxidation and electrical conduction in a single gold nanowire.
AB  - The resistance, R, of single gold nanowires was measured in situ during
      electrooxidation in aqueous 0.10 M sulfuric acid. Electrooxidation caused the
      formation of a gold oxide that is approximately 0.8 monolayers (ML) in thickness
      at +1.1 V vs saturated mercurous sulfate reference electrode (MSE) based upon
      coulometry and ex situ X-ray photoelectron spectroscopic analysis. As the gold
      nanowires were electrooxidized, R increased by an amount that depended on the
      wire thickness, ranging from Delta R/ R 0.10V = 14% for a 63 nm (h) x 200 nm (w)
      wire to 57% for an 18 nm (h) x 95 nm (w) wire at +1.1 V. These nanowires were
      millimeters in total length, but just 46 microm lengths were exposed to the
      electrolyte solution. The oxidation process and the accompanying increase in R
      were reversible: Reduction of the oxide at +0.10 V resulted in recovery of the
      reduced wire R except for a small resistance offset caused by the dissolution of
      approximately 0.4 ML of gold during each oxidation/reduction cycle. The measured
      increase in R during oxidation exceeds by a factor of 4 the predicted increases
      in R associated with the reduction in cross-sectional area of the nanowire and
      the expected decrease in the specular scattering parameter, p, at the gold-oxide
      interface at wire surfaces. We propose that this anomalous increase in R is
      caused by infiltration of the oxide into the nanowire at grain boundaries.

PMID- 18712932
TI  - Flux quantization effects in InN nanowires.
AB  - InN nanowires, grown by plasma-enhanced molecular beam epitaxy, were investigated
      by means of magnetotransport. By performing temperature-dependent transport
      measurements and current measurements on a large number of nanowires of different
      dimensions, it is proven that the carrier transport mainly takes place in a tube
      like surface electron gas. Measurements on three representative nanowires under
      an axially oriented magnetic field revealed pronounced magnetoconductance
      oscillations with a periodicity corresponding to a single magnetic flux quantum.
      The periodicity is explained by the effect of the magnetic flux penetrating the
      coherent circular quantum states in the InN nanowires, rather than by Aharonov
      Bohm type interferences. The occurrence of the single magnetic flux quantum
      periodicity is attributed to the magnetic flux dependence of phase-coherent
      circular states with different angular momentum quantum numbers forming the one
      dimensional transport channels. These phase coherent states can exist because of
      the almost ideal crystalline properties of the InN nanowires prepared by self
      assembled growth.

PMID- 18712933
TI  - Benzoic acid derivatives from Piper species and their antiparasitic activity.
AB  - Piper glabratum and P. acutifolium were analyzed for their content of main
      secondary constituents, affording nine new benzoic acid derivatives (1, 2, 4, 5,
      7, and 10-13), in addition to four known compounds (3, 6, 8, and 9). Their
      structures were elucidated on the basis of spectroscopic data. Riguera ester
      reactions and optical rotation measurements established the new compounds as
      racemates. In the search for antiparasitic agents, the compounds were evaluated
      in vitro against the promastigote forms of Leishmania spp., Trypanosoma cruzi,
      and Plasmodium falciparum. Among the evaluated compounds, methyl 3,4-dihydroxy-5
      (3'-methyl-2'-butenyl)benzoate (7) exhibited leishmanicidal effect (IC50 13.8
      18.5 microg/mL) against the three Leishmania strains used, and methyl 3,4
      dihydroxy-5-(2-hydroxy-3-methylbutenyl)benzoate (1), methyl 4-hydroxy-3-(2
      hydroxy-3-methyl-3-butenyl)benzoate (3), and methyl 3,4-dihydroxy-5-(3-methyl-2
      butenyl) benzoate (7) showed significant trypanocidal activity, with IC50 values
      of 16.4, 15.6, and 18.5 microg/mL, respectively.

PMID- 18712934
TI  - Automation of solid-phase microextraction in high-throughput format and
      applications to drug analysis.
AB  - The automation of solid-phase microextraction (SPME) coupled to liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) was accomplished using a 96
      multiwell plate format, a SPME multifiber device, two orbital shakers, and a
      three-arm robotic system. Extensive optimization of the proposed setup was
      performed including coating selection, optimization of the fiber coating
      procedure, confirmation of uniform agitation in all wells, and the selection of
      the optimal calibration method. The system allows the use of pre-equilibrium
      extraction times with no deterioration in method precision due to reproducible
      timing of extraction and desorption steps and reproducible positioning of all
      fibers within the wells. The applicability of the system for the extraction of
      several common drugs is demonstrated. The optimized multifiber SPME-LC-MS/MS was
      subsequently fully validated for the high-throughput analysis of diazepam,
      lorazepam, nordiazepam, and oxazepam in human whole blood. The proposed method
      allowed the automated sample preparation of 96 samples in 100 min, which
      represents the highest throughput of any SPME technique to date, while achieving
      excellent accuracy (87-113%), precision (<or=20% RSD), and sensitivity (limit of
      quantitation 4 ng/mL). Automated SPME provides unique advantages over automated
      solid-phase extraction (SPE) including lower cost, the ability to quantitatively
      determine free and total drug concentrations in a single biofluid sample, and the
      ability to directly process whole blood samples with absolutely no sample
      pretreatment required.

PMID- 18712935
TI  - Monitoring of real-time streptavidin-biotin binding kinetics using droplet
      microfluidics.
AB  - Rapid kinetic measurements are important in understanding chemical interactions
      especially for biological molecules. Herein, we present a droplet-based
      microfluidic platform to study streptavidin-biotin binding kinetics with
      millisecond time resolution. With integration of a confocal fluorescence
      detection system, individual droplets can be monitored and characterized online
      to extract kinetic information. Using this approach, binding kinetics between
      streptavidin and biotin were observed via fluorescence resonance energy transfer.
      The binding rate constant of streptavidin and biotin was found to be in a range
      of 3.0 x 10 (6)-4.5 x 10 (7) M (-1) s (-1).

PMID- 18712937
TI  - Influence of surfactant counterions during electrophoretic particle deposition.
AB  - This study demonstrates the influence of a cationic surfactant on colloidal
      particle electrodeposition (migration and adhesion). Three cetyltrimethylammonium
      salts (CTA+) with various counterions (bromide, chloride, and hydrogenosulphate)
      were studied. Particle transport toward the electrode was driven by the
      electrophoretic force. Once particles reached the electrode, a wide variety of
      behaviors were observed, depending on surfactant concentration and counterions:
      particles would stick permanently or slide along the electrode surface, remain or
      detach upon potential switching, act as nuclei for aggregate growth, or produce a
      homogeneous particle film. The experimental results also demonstrate the specific
      influence of surfactant counterions on the deposited film morphology.

PMID- 18712936
TI  - Evolution reversed: the ability to bind iron restored to the N-lobe of the murine
      inhibitor of carbonic anhydrase by strategic mutagenesis.
AB  - The murine inhibitor of carbonic anhydrase (mICA) is a member of the superfamily
      related to the bilobal iron transport protein transferrin (TF), which binds a
      ferric ion within a cleft in each lobe. Although the gene encoding ICA in humans
      is classified as a pseudogene, an apparently functional ICA gene has been
      annotated in mice, rats, cows, pigs, and dogs. All ICAs lack one (or more) of the
      amino acid ligands in each lobe essential for high-affinity coordination of iron
      and the requisite synergistic anion, carbonate. The reason why ICA family members
      have lost the ability to bind iron is potentially related to acquiring a new
      function(s), one of which is inhibition of certain carbonic anhydrase (CA)
      isoforms. A recombinant mutant of the mICA (W124R/S188Y) was created with the
      goal of restoring the ligands required for both anion (Arg124) and iron (Tyr188)
      binding in the N-lobe. Absorption and fluorescence spectra definitively show that
      the mutant binds ferric iron in the N-lobe. Electrospray ionization mass
      spectrometry confirms the presence of both ferric iron and carbonate. At the
      putative endosomal pH of 5.6, iron is released by two slow processes indicative
      of high-affinity coordination. Induction of specific iron binding implies that
      (1) the structure of mICA resembles those of other TF family members and (2) the
      N-lobe can adopt a conformation in which the cleft closes when iron binds.
      Because the conformational change in the N-lobe indicated by metal binding does
      not impact the inhibitory activity of mICA, inhibition of CA was tentatively
      assigned to the C-lobe. Proof of this assignment is provided by limited trypsin
      proteolysis of porcine ICA.

PMID- 18712938
TI  - Submicron scale patterning in sintered silica colloidal crystal films using a
      focused ion beam.
AB  - Focused ion beam milling is used to fabricate micron and submicron scale patterns
      in sintered silica colloidal crystal films. Rectangular cavities with both solid
      and porous boundaries, fluidic channels, and isolation of a small number of
      packed spheres are patterned. The ion beam can pattern sintered films of
      individual submicron size spheres and create patterns that cover up to 40 mum in
      less than 15 min. The experiments in this work indicate that the amount of
      redeposited material on the surface of a milled cavity determines whether the
      surface will be porous or solid. FIB direct patterning has applications in
      colloidal crystal based lithography, integrated photonic devices, optofluidic
      devices, and micrototal-analytical systems.

PMID- 18712939
TI  - Talent identification and development programmes in sport : current models and
      future directions.
AB  - Many children strive to attain excellence in sport. However, although talent
      identification and development programmes have gained popularity in recent
      decades, there remains a lack of consensus in relation to how talent should be
      defined or identified and there is no uniformly accepted theoretical framework to
      guide current practice. The success rates of talent identification and
      development programmes have rarely been assessed and the validity of the models
      applied remains highly debated. This article provides an overview of current
      knowledge in this area with special focus on problems associated with the
      identification of gifted adolescents. There is a growing agreement that
      traditional cross-sectional talent identification models are likely to exclude
      many, especially late maturing, 'promising' children from development programmes
      due to the dynamic and multidimensional nature of sport talent. A conceptual
      framework that acknowledges both genetic and environmental influences and
      considers the dynamic and multidimensional nature of sport talent is presented.
      The relevance of this model is highlighted and recommendations for future work
      provided. It is advocated that talent identification and development programmes
      should be dynamic and interconnected taking into consideration maturity status
      and the potential to develop rather than to exclude children at an early age.
      Finally, more representative real-world tasks should be developed and employed in
      a multidimensional design to increase the efficacy of talent identification and
      development programmes.

PMID- 18712940
TI  - Heat shock protein 72 response to exercise in humans.
AB  - Heat shock protein (Hsp) 72 is a unique, ubiquitous molecule. In vitro and in
      vivo animal models have shown that increased Hsp 72 is associated with improved
      cellular survivability and tolerance to stressors. The primary focus of this
      article is to review the Hsp 72 protein response to exercise in humans. Various
      mechanisms regulate post-transcriptional activity and therefore measurement of
      messenger RNA (mRNA) does not necessarily represent the level of functional Hsp
      72. For this reason, this article incorporates only a few studies that assessed
      Hsp 72 mRNA response to exercise. Although this article focuses on human studies,
      it also includes some key animal studies to provide insight into the mechanisms
      of the response of Hsp 72 to stress.Intra- (IC) and extracellular (EC) Hsp 72
      have different functions. IC Hsp 72 confers cellular protection from subsequent
      stressors, while EC Hsp 72 has a whole-body systemic role in antigen presentation
      and immunity. An acute exercise bout stimulates an increase in both IC and EC Hsp
      72. Long-term training and improved fitness increases the rate of availability of
      IC Hsp 72 in response to stress. Other factors that affect Hsp 72 production
      include environmental factors, exercise mode, duration and intensity, age,
      estrogen, and anti-oxidant and glycogen availability. The functions and roles of
      Hsp 72 also depend on the tissue of origin. This article describes the Hsp 72
      response to exercise in relation to the tissue assayed (i.e. skeletal muscle vs
      lymphocyte) and the origin of the sample (i.e. venous vs arterial serum).
      Collectively, the reviewed studies reveal exciting and novel research that
      encourages future investigation in this area.

PMID- 18712942
TI  - Is active commuting the answer to population health?
AB  - This brief review examines whether active commuting is an effective method of
      controlling the current obesity epidemic and enhancing the cardiovascular health
      of the population. Of the many potential methods of active commuting, walking and
      cycling are the usual choices. Children and adolescents prefer cycling, but for
      adults issues of safety, cycle storage and company dress codes make walking the
      preferred option, particularly in North American cities, where urban design and
      weather conditions often do not favour cycling. Active transportation is more
      frequent in some European countries with dedicated cycle and pedestrian paths,
      but in most developed societies, active transportation has declined in recent
      years.Attempts to increase walking behaviour in the sedentary population have had
      only limited success to date. A weekly gross energy expenditure of at least 4 MJ
      is recommended to reduce all-cause and cardiovascular mortality. This can be
      achieved by walking 1.9 km in 22 minutes twice per day, 5 days per week, or by
      cycling at 16 km/h for 11 minutes twice per day, 5 days per week. When engaged in
      level walking, the intensity of effort may be adequate for cardiovascular benefit
      in older adults, but in fit young workers, it is necessary to either increase the
      pace or choose a hilly route in order to induce cardio-respiratory benefit; in
      contrast, cycling is likely to provide an adequate cardiovascular stimulus even
      for young adults.Empirical data to date have yielded mixed results: a reduced all
      cause and cardiovascular mortality has been observed more frequently in cyclists
      than in walkers, and more frequently in women and older men than in young active
      commuters. More information is needed concerning the typical weekly dose of
      activity provided by active commuting, and the impact of such commuting on
      overall attitudes towards physical activity. It is also necessary to find better
      methods of involving the sedentary population, through both counselling and
      changes in urban design.

PMID- 18712943
TI  - Effectiveness of foot orthoses for treatment and prevention of lower limb
      injuries : a review.
AB  - Healthcare professionals prescribe foot orthoses (FOs) for treatment and
      prevention of lower limb injuries, but previous reviews of the effectiveness of
      FOs have been inconclusive. We have therefore performed a review emphasizing the
      magnitude of treatment effects to evaluate the clinical effectiveness of FOs in
      the treatment and prevention of lower limb injuries.Qualifying studies were
      mainly controlled trials, but some uncontrolled clinical trials of patients with
      chronic injuries were analysed separately. Injuries included plantar fasciitis,
      tibial stress fractures and patellofemoral pain syndrome; these were included
      because of the large treatment costs for these frequent injuries in New Zealand.
      Outcomes were pain, comfort, function and injury status. Continuous measures were
      expressed as standardized differences using baseline between-subject standard
      deviations, and magnitudes were inferred from the intersection of 90% confidence
      intervals with thresholds of a modified Cohen scale. Effects based on frequencies
      were expressed as hazard ratios and their magnitudes were inferred from
      intersection of confidence intervals with a novel scale of thresholds.The effects
      of FOs for treatment of pain or injury prevention were mostly trivial. FOs were
      not effective in treating or preventing patellofemoral pain syndrome. Some
      studies showed moderate effects for treatment of plantar fasciitis. Only a few
      studies showed moderate or large beneficial effects of FOs in preventing
      injuries.Customized semi-rigid FOs have moderate to large beneficial effects in
      treating and preventing plantar fasciitis and posterior tibial stress fractures,
      and small to moderate effects in treating patellofemoral pain syndrome. Given the
      limited randomized controlled trials or clinical controlled trials available for
      the injuries of interest, it may be that more or less benefit can be derived from
      the use of FOs, but many studies did not provide enough information for the
      standardized effect sizes to be calculated. Further research with randomized
      controlled trials is needed to establish the clinical utility of a variety of FOs
      for the treatment and prevention of various lower limb injuries.

PMID- 18712941
TI  - Beneficial effects of exercise on muscle mitochondrial function in diabetes
      mellitus.
AB  - The physiopathology of diabetes mellitus has been closely associated with a
      variety of alterations in mitochondrial histology, biochemistry and function.
      Generally, the alterations comprise increased mitochondrial reactive oxygen and
      nitrogen species (RONS) generation, resulting in oxidative stress and damage;
      decreased capacity to metabolize lipids, leading to intramyocyte lipid
      accumulation; and diminished mitochondrial density and reduced levels of
      uncoupling proteins (UCPs), with consequent impairment in mitochondrial function.
      Chronic physical exercise is a physiological stimulus able to induce
      mitochondrial adaptations that can counteract the adverse effects of diabetes on
      muscle mitochondria. However, the mechanisms responsible for mitochondrial
      adaptations in the muscles of diabetic patients are still unclear. The main
      mechanisms by which exercise may be considered an important non-pharmacological
      strategy for preventing and/or attenuating diabetes-induced mitochondrial
      impairments may involve (i) increased mitochondrial biogenesis, which is
      dependent on the increased expression of some important proteins, such as the
      'master switch' peroxisome proliferator-activated receptor (PPAR)-gamma
      coactivator-1alpha (PGC-1alpha) and heat shock proteins (HSPs), both of which are
      severely downregulated in the muscles of diabetic patients; and (ii) the
      restoration or attenuation of the low UCP3 expression in skeletal muscle
      mitochondria of diabetic patients, which is suggested to play a pivotal role in
      mitochondrial dysfunction.There is evidence that chronic exercise and lifestyle
      interventions reverse impairments in mitochondrial density and size, in the
      activity of respiratory chain complexes and in cardiolipin content; however, the
      mechanisms by which chronic exercise alters mitochondrial respiratory parameters,
      mitochondrial antioxidant systems and other specific proteins involved in
      mitochondrial metabolism in the muscles of diabetic patients remain to be
      elucidated.

PMID- 18712944
TI  - The functional effects of physical exercise training in frail older people : a
      systematic review.
AB  - This systematic review describes the effect of exercise training on physical
      performance in frail older people. Randomized controlled trials were identified
      from searches in PubMed, EMBASE and CENTRAL from January 1995 through August
      2007. Two reviewers independently screened the trials for eligibility, rated
      their quality, and extracted data. Randomized controlled trials that examined the
      effects on performance-based measures of physical function among frail older
      adults were included. The systematic search identified 20 studies, examining 23
      different exercise programmes. The methodological quality score (0-9) of the
      trials ranged from 2 to 7 points. Sixteen of the studies were scored as high
      quality. There was a large variety in the studies concerning sample size, degree
      of frailty, types of interventions and types of assessments. The majority of the
      programmes were facility-based, group-exercise programmes that were performed
      three times a week for 45-60 minutes. The intervention programmes comprised
      resistance training (n = 9), Tai Chi training (n = 2), or multi-component
      training (n = 12). Six of the total selected 20 studies did not find a beneficial
      exercise effect on functional performance. This systematic review suggests that
      older adults with different levels of abilities can improve their functional
      performance by regular exercise training. To determine the most appropriate
      design of the exercise programme (type, intensity, frequency and duration of
      exercise) for functional improvement or prevention of loss of function, more high
      quality trials are needed in which different training protocols are compared.

PMID- 18712945
TI  - A kinetic model for the relative contribution of waterborne and dietary cadmium
      and zinc in the common carp (Cyprinus carpio).
AB  - In this work, the uptake and whole-body accumulation of Cd and Zn by the common
      carp from water, diet, and a combination of both was studied using the
      radioactive tracers 09Cd and 65Zn. A three-compartment pharmacokinetic model was
      constructed and revealed metal- and exposure route-dependent accumulation
      profiles. Under the tested exposure conditions in water (0.1 microM Cd and 1
      microM Zn), only 0.1 and 0.07%, respectively, of the total Cd and Zn load that
      passed the branchial surfaces was accumulated by the carp. In contrast, the carp
      accumulated 20 and 29% of the total ingested Cd and Zn load (mean concentrations
      in food of newly accumulated metals were 2.24 +/- 0.29 and 19.91 +/- 2.89 nmol/g
      wet weight, respectively). However, the contribution of the waterborne metals to
      the whole-body metal accumulation was higher than the metal uptake from food. The
      constructed model was used to simulate the effect of variable assimilation
      efficiency (AE) values on the relative importance of dietary Cd and Zn exposure
      to the overall metal accumulation in common carp. This simulation was performed
      under a realistic exposure scenario and with Cd and Zn AE values ranging from 5
      to 95%. Dissolved Zn levels were higher and Cd levels lower compared to the
      laboratory experiments. Levels in the midge larvae were much higher. The results
      show that under these conditions, even at the lowest Cd and Zn AEs, almost 40% of
      the total body Cd and Zn concentrations originated from dietary Cd and Zn
      exposure. Taking into account the Cd and Zn AE of the laboratory experiments,
      respectively, 31 and 55%, more than 85% of the total body Cd and Zn was taken up
      from the food.

PMID- 18712946
TI  - Measuring pyrethroids in sediment pore water using matrix-solid phase
      microextraction.
AB  - Pyrethroids are hydrophobic insecticides commonly used in both agricultural and
      urban environments. Their high toxicity to aquatic organisms, including benthic
      invertebrates, and detection in the sediment at many locations in California,
      U.S.A., have spawned interest in understanding their bioavailability in bed
      sediments. A recent study showed good correlation between uptake of 14C
      permethrin in Chironomus tentans and solid-phase microextraction (SPME) fibers in
      sediments. The present study was directed at the development of an SPME technique
      applicable to trace levels of nonlabeled pyrethroids in sediment. Disposable
      polydimethylsiloxane fibers were used to detect freely dissolved pore-water
      concentrations of bifenthrin, fenpropathrin, cis-permethrin, trans-permethrin,
      cyfluthrin, cypermethrin, and esfenvalerate under agitated and static conditions.
      Partition equilibrium between fiber and sediment was reached in <5 d when the
      samples were agitated on a shaker at low speed, while much longer times (>23 d)
      were needed without agitation. Polydimethylsiloxane to water partition ratios
      (K(PDMS)) of the seven pyrethroids were measured separately and ranged from 2.83
      x 10(5) to 1.89 x 10(6). When applied to field-contaminated sediments, agitated
      matrix-SPME was able to detect pore-water concentrations as low as 0.1 ng/L. The
      method developed in the present study may be coupled with bioassays to gain
      mechanistic understanding of factors affecting pyrethroid toxicities, and applied
      to field samples to better predict sediment toxicities from pyrethroid
      contamination.

PMID- 18712947
TI  - Substance or space? The relative importance of substance properties and
      environmental characteristics in modeling the fate of chemicals in Europe.
AB  - The relative influence of substance properties and of environmental
      characteristics on the variation in the environmental fate of chemicals was
      studied systematically and comprehensively. This was done by modeling
      environmental concentrations for 200 sets of substance properties, representative
      of organic chemicals used, and 137 sets of environmental characteristics,
      representative of regions in Europe of 250 x 250 km. Since it was expected that
      the model scale has an influence on the predicted concentration variations, the
      calculations were repeated for regions with a 100 x 100 km and 50 x 50 km area.
      Stepwise multiple regression analysis was performed to determine the contribution
      of each of the individual input parameters on the total concentration variation.
      Depending on the scenario, the range in predicted environmental concentrations
      spreads from two up to nine orders of magnitude. In accord with earlier studies,
      variation in the fate of chemicals in the environment appeared to depend mainly
      on substance-specific partition coefficients and degradation rates. For the
      estimation of soil and water concentrations with direct emissions to these
      compartments, however, the influence of spatial variation in environmental
      characteristics can mount up to two orders of magnitude, a range that can be
      significant to account for in certain model applications. Concentration
      differences in water and soil are predicted to be larger if a smaller region is
      applied in the model calculations, and the relative influence of environmental
      characteristics on the total variation increases on a more detailed spatial
      scale. It is argued that the influence of environmental characteristics as
      predictors of exposure concentrations of chemicals deserves better attention in
      comparative risk assessment with conventional nonspatial multimedia box models.

PMID- 18712948
TI  - Patterns of infection by lungworms, Rhabdias ranae and Haematoloechus spp., in
      northern leopard frogs: a relationship between sex and parasitism.
AB  - We examined a population of northern leopard frogs to determine whether sex
      biases in investment in immunity, previously reported for this host species under
      controlled exposures to lung nematodes, is predictive of patterns of parasitism
      in nature. We examined Rhabdias ranae and Haematoloechus spp. infections in 74
      breeding adult, 28 non-breeding adult, and 53 juvenile frogs. Contrary to our
      predictions, R. ranae prevalence and mean abundance were higher in breeding
      female frogs (prevalence: 39.4%, abundance: 3.05 +/- 0.85) than on breeding males
      (prevalence: 26.0%, abundance: 1.17 +/- 0.52), although no sex bias was observed
      among non-breeding adults or juvenile frogs. Female frogs also carried larger R.
      ranae worms, on average, than did males (females: 6407.38 microm +/- 153.80;
      males: 5198 microm +/- 131.09), regardless of age or breeding condition. We
      observed no sex-linked patterns of parasitism by Haematoloechus spp. worms in
      either adult or juvenile frogs. Alternative hypotheses, such as differences among
      sexes in the selection of thermal clines for hibernation, may explain the
      observed female bias in parasitism by nematode lungworms in nature and, thus,
      need to be considered.

PMID- 18712949
TI  - Fatty acid composition of the estuarine amphipod, Melita plumulosa (Zeidler):
      link between diet and fecundity.
AB  - The influence of various diets on the survival, fecundity, and the
      polyunsaturated fatty acid (PUFA) composition of the benthic estuarine amphipod
      Melita plumulosa (Zeidler) in laboratory cultures were determined. Apart from a
      natural silty sediment, six commercial food supplements were examined: an omega-6
      PUFA enriched Spirulina-based dry powder, Sera micron; a shrimp-based pellet
      food; an omega-3 PUFA enriched algal paste, Rotiselco-ALG; an omega-6 PUFA
      enriched algal dry powder, AlgaMac-ARA (arachidonic acid); flaxseed meal; and an
      omega-3 PUFA enriched dry powder, Frippak. We have previously established that M.
      plumulosa cultures perform poorly and eventually decline if provided with silty
      sediment alone, but will thrive if supplemented with Sera micron. Conversely, if
      the amphipods are cultured on a nutrient-depleted sand substrate, Sera micron
      alone does not constitute an adequate feed. The major difference in the fatty
      acid composition of M. plumulosa cultured on silty sediment compared to amphipods
      cultured on a sand substrate and both fed Sera micron was an increase in the
      ratio of omega-3 to omega-6 PUFAs, indicating that the silty sediment provides
      additional food sources rich in omega-3 PUFAs. Furthermore, amphipods cultured in
      sand and fed any of the three algal-based foods or the Frippak powder as the sole
      food source had poor survival rates, although Sera micron maintained the best
      survival-this was attributed to it containing high amounts of beta-carotene and
      terpenoids. Melita plumulosa fed a mixture of Sera micron in conjunction with the
      omega-3 PUFA enriched Rotiselco-ALG and cultured on a silty substrate were found
      to have good fecundity with low variability.

PMID- 18712950
TI  - Assessment of digenean parasitism in Nassarius reticulatus (L.) along the
      Portuguese coast: evaluation of possible impacts on reproduction and imposex
      expression.
AB  - A survey was performed between June and September 2006 along the Portuguese coast
      to assess the prevalence of digenean parasitism in the netted whelk Nassarius
      reticulatus, a bioindicator of tributyltin (TBT) pollution. It was also intended
      to evaluate the effect of parasites on the reproduction of this gastropod species
      and their interference on the development of imposex (the superimposition of male
      characters onto prosobranch females) and male penis, based on field data. Five
      digenean species (Lepocreadium album, Gynaecotyla longiintestinata, Himasthla
      quissetensis, Diphtherostomum brusinae, and Cardiocephalus longicollis), plus 1
      unidentified species, were found to infect N. reticulatus. Parasitism was spread
      along the Portuguese coast, but the higher values of prevalence were found in
      sheltered inshore areas where up to 67.4% of the animals were affected per
      sampling station. Parasitism has a castrating impact on the whelks and a reducing
      effect on male penis size, which causes serious disorders in the reproduction of
      N. reticulatus and may have an important impact in its population dynamics.
      However, no relationship between imposex severity and parasite infestation was
      found.

PMID- 18712951
TI  - Maternal thrombophilias are associated with specific placental lesions.
AB  - Maternal floor infarction (MFI), massive perivillous fibrin deposition (MPVFD),
      and fetal thrombotic vasculopathy (FTV) are specific placental lesions with
      associations to recurrent adverse fetal outcomes and with maternal thrombophilia.
      We studied the frequency of a range of acquired and genetic maternal
      thrombophilias in MFI (40 cases), MPVFD (87 cases), FTV (7 cases), and FTV+MPVFD
      (4 cases). Thrombophilias were identified in 16 (40%), 20 (23%), 5 (71%), and 2
      (50%) of these lesions, respectively. Seventy-seven percent of the identified
      thrombophilias were genetic, and 23% were acquired. The most common genetic
      thrombophilia was protein S deficiency, which constituted 14 of the 36 genetic
      thrombophilias (39%). We advocate full maternal thrombophilia testing when the
      diagnosis of MFI, MPVFD, and FTV is made by placental pathology examination.
      Because of the possible contribution of paternal thrombophilic mutations to the
      fetal genotype, it would be desirable to test the whole family as well.

PMID- 18712952
TI  - Morphology and etiology meet at the maternal-fetal interface.
AB  - Molecular diagnostic testing is leaving its mark in many areas of medicine; no
      less in perinatal pathology. This CONTEXT article uses the finding of Gogia and
      Machin in this issue of Pediatric and Developmental Pathology that genetic or
      acquired thrombophilias are associated with fetal thrombotic vasculopathy,
      massive perivillous fibrin deposition, and maternal floor infarction as an
      example of how molecular testing is providing possible etiologies for entities
      that heretofore have largely been only morphologic diagnoses. 

PMID- 18712954
TI  - The APJCP as the official journal of the UICC-Asian Regional Office for Cancer
      Control and the Asian Pacific Organization for Cancer Prevention and Control.

PMID- 18712955
TI  - Cancer registration literature update (2006-2008).
AB  - Using Cancer Registration and Registry as search items with PubMed, a survey of
      the relevant literature for the years 2006-2008 was performed. A total of 207
      abstracts were scanned for core findings and classified under general incidence
      and mortality, methodology and specific organ headings, these accounting for 27%,
      5% and 68% of papers, respectively. Further sub-division into geographical area
      and country showed 34% from Europe, less than 1% from Africa, 42% from Asia
      (almost half in the APJCP), 2% from Australasia and the remaining 21% from the
      Americas. Breast cancer was the most common specific cancer covered, followed by
      colorectal and childhood, then lung and urinary tract, but clear differences were
      noted in the focus of different countries, partially reflecting variation in
      prevalence. The distributions across and within continents point to geographical
      areas and countries in which assistance might allow a more comprehensive picture
      of cancer incidence and mortality to be generated, facilitating worldwide efforts
      for cancer control. Variation within countries also appears to require more
      emphasis in the future.

PMID- 18712956
TI  - Dietary agents in prevention of prostate cancer.
AB  - Prostate cancer is the second leading cause of internal malignancy among men
      worldwide, with an annual incidence of 679,000 cases, and an annual mortality
      load of 220,000 deaths, making it the sixth leading cause of cancer mortality
      among men. It is generally on the increase. Environmental and lifestyle factors
      may have an aetiological role in prostate cancer and hence may provide potential
      targets for future intervention. In fact, because of the disease high prevalence,
      slowly progressive nature, and long latency prostate cancer is a very good
      candidate for chemoprevention. Dietary agents have gained considerable attention
      as chemopreventive agents against prostate cancer. The methodology for this
      review included computerized literature searches of the PubMed database using the
      keywords 'chemoprevention of prostate cancer' from 1992 to 2007. This mini-review
      examines the influence of plant-derived dietary agents for which articles
      reported statistically significant effects in the management of prostate cancer.

PMID- 18712957
TI  - Food as medicine: potential therapeutic tendencies of plant derived polyphenolic
      compounds.
AB  - The last two decades have witnessed a major drift in the interests of the
      scientific community towards explaining better means to containing the health
      risks of the human race. The century old chemotherapies against various disorders
      have never been a success, albeit not a total failure. Such therapies have a
      major drawback of side effects that give rise to unseen disorders that emerge as
      a new challenge. In this regard, the concept of foodstuffs as natural medicines
      is very attractive. Epidemiological studies suggest that the vegeteranian food
      habit is associated with reduced risk of cancer, cardiovascular and
      neurodegenerative disorders. Consistent with this hypothesis is the fact that the
      incidence of these disorders is least in Asian populations where fruits,
      vegetables and spices are the major elements in the human diet. Recent research
      has shown that plant-derived polyphenolic compounds are promising nutraceuticals
      for control of various disorders such as cardiovascular,neurological and
      neoplastic disease. The richness of the polyphenolic contents of green tea and
      red wine has made them popular choice for associated anticancer and
      cardiovascular health benefits. The present article is a brief review of the
      promises plant polyphenols, bioactive components of our food, hold for the
      future.

PMID- 18712958
TI  - Survival analysis of Malaysian women with breast cancer: results from the
      University of Malaya Medical Centre.
AB  - BACKGROUND: Breast cancer is the commonest cancer amongst Malaysian women but
      local survival data are scarce. The present study was therefore conducted to
      assess overall survival and prognostic factors in Malaysian breast cancer
      patients. METHODS: The research sample was a prospective cohort of 413 patients
      diagnosed with breast cancer in the University of Malaya Medical Centre between
      1993 to 1997. Survival data were obtained from the National Registry of Birth and
      Deaths in December 2000. The clinico-pathological variables studied were age,
      ethnic group, stage, tumour size, lymph node status, oestrogen receptor status
      and grade. The data were analysed utilizing Splus statistical software. The
      important prognostic factors were identified by fitting the Cox's proportional
      hazard model to the data set. Survival probabilities were estimated using the
      Kaplan-Meier method and differences were compared by the log-rank test. RESULTS:
      The overall 5-year survival was 59.1%. The Cox's proportional hazard model
      identified stage, lymph node status, size and grade as factors that correlated
      with prognosis. Age was not a significant prognostic factor. The Cox regression
      model by stepwise selection showed stage, nodal status and grade of tumour to be
      independent prognostic factors, whereas ethnicity, age and ER status were not.
      INTERPRETATION: The overall survival in our centre was low. Recognizing factors
      that affect prognosis of breast cancer patients in Malaysia may improve delivery
      of health care to at-risk groups by strategizing interventions as survival
      depends on early detection and effective treatment.

PMID- 18712959
TI  - Genetic polymorphisms of methylenetetrahydrofolate reductase and susceptibility
      to colorectal cancer.
AB  - OBJECTIVES: To study the relation between genetic polymorphisms of
      methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the
      susceptibility of colorectal cancer. METHODS: We conducted a case-control study
      with 315 cases of colorectal cancer and 371 population-based controls in Jiangsu
      province, China. The epidemiological data were collected, and DNA of peripheral
      blood leukocytes was obtained from all of the subjects. MTHFR C677T and A1298C
      genotypes were detected by the PCR-RFLP method. RESULTS: (1) When men and women
      were assessed together, the frequencies of the MTHFR C677T and A1298 genotypes or
      their alleles were not significantly different between controls and colon cancer
      or rectal cancer cases. No significant relation was observed between MTHFR C677T
      or A1298C polymorphisms and colon or rectal cancer susceptibility. (2) Among
      males, individuals who had MTHFR C677T T/T genotype were at a significantly
      higher risk of developing colon cancer (age-, residence-, smoking-, alcohol
      drinking-, tea consumption-adjusted OR=2.15, 95%CI: 1.07-4.33) compared with
      those who had C677T C allele. Individuals who had C677T T/T and A1298C A/A
      genotypes were at an increased risk of developing colon cancer (adjusted OR=2.64,
      95%CI: 1.20-5.81) compared with those with C677T C allele and A1298C A/A
      genotypes among males. On the contrary, individuals who had C677T T/T and A1298C
      A/A genotypes were at an decreased risk of developing rectal cancer (adjusted
      OR=0.47, 95%CI: 0.22-1.03). CONCLUSIONS: These results in the present study
      suggested that polymorphisms of the MTHFR C677T could influence susceptibility to
      colon or rectal cancer and that there was a coordinated effect between MTHFR
      A1298C A/A and C677T T/T genotypes among males.

PMID- 18712960
TI  - Factors predicting occult invasive carcinoma in women undergoing a 'see and
      treat' approach.
AB  - This study was undertaken to evaluate the incidence and independent predictors of
      unexpected invasive cancer of cervix in women with high-grade squamous
      intraepithelial lesions (HSIL) on Pap smear who had undergone a 'see and treat'
      approach. Women with HSIL on cervical cytology undergoing colposcopy, followed by
      loop electrosurgical excision procedure (LEEP) at Chiang Mai University Hospital
      between January 2001 and April 2006 were analyzed. During the study period, 446
      women were identified. Mean age was 45.6 years (range, 25-75 years). One hundred
      and twenty-one (27.1%) women were postmenopausal. Unsatisfactory colposcopy was
      observed in 357 (80.0%) women. Of the 446 women, 76 (17.04%, 95% CI=13.67 to
      20.86) had invasive lesions on LEEP specimens. Multivariate analysis revealed
      that unsatisfactory colposcopy and premenopausal status were statistically
      significant independent predictors for invasive lesions in a 'see and treat' LEEP
      with an adjusted odds ratio of 4.68 (95%CI=1.82 to 12.03, P<0.01) and 2.10
      (95%CI=1.12 to 3.94, P=0.02), respectively. In conclusion, occult invasive lesion
      of the cervix was noted in 17% of women with HSIL Pap smear who underwent a 'see
      and treat' approach at our institute. Unsatisfactory colposcopy and premenopausal
      status were significant independent predictors of having such lesion.

PMID- 18712961
TI  - Incidence and predictors of febrile morbidity after radical hysterectomy and
      pelvic lymphadenectomy for early stage cervical cancer patients.
AB  - This study was undertaken to evaluate the incidence and independent predictors
      for febrile morbidity after radical hysterectomy and pelvic lymphadenectomy.
      Patients with FIGO stage IB-IIA cervical cancers who had undergone RHPL at Chiang
      Mai University Hospital between January 2003 and December 2005, were reviewed.
      The clinical variables including the age at diagnosis, menopausal status, body
      mass index, previous cervical conization, tumor size, preoperative chemotherapy,
      preoperative anemia, operative time, and estimated blood loss were analyzed for
      prediction of postoperative febrile morbidity. During the study period, 357 women
      were reviewed. The mean age was 44.7 years. Sixty-five (18.2%) women were
      postmenopausal. The majority of women (77.3%) were in FIGO stage IB1. The most
      common histology was squamous cell carcinoma (69.2%). Febrile morbidity was noted
      in 94 women (26.3%, 95% CI= 21.8-31.2) in whom 25 (7.0%) had urinary tract
      infection (19), abdominal wound infection (4), and vaginal cuff infection (2),
      respectively. Only massive blood loss (>1,500 ml) was noted as the significantly
      independent predictor for febrile morbidity (aOR= 2.7, 95% CI=1.1-6.6, P=0.028).
      In conclusion, approximately one-fourth of the women undergoing RHPL at our
      institute had postoperative febrile morbidity. Only massive blood loss is a
      significant predictor for this complication.

PMID- 18712962
TI  - Associations between a PTPN11 polymorphism and gastric atrophy--opposite in
      Uzbekistan to that in Japan.
AB  - Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) of
      gastric epithelial cells interacts with cagA from Helicobacter pylori (H.
      pylori). Our previous studies found the AA genotype of a G/A single nucleotide
      polymorphism at intron 3 (rs2301756) of PTPN11 gene, which encodes SHP-2, to be
      associated with a lower risk of gastric atrophy. The present study aimed to
      examine the association with gastric atrophy among the subjects of a case-control
      study of peptic ulcer disease (PUD) conducted in the Uzbek Republic. Cases were
      95 patients (61 males and 34 females) with PUD aged 16 to 85 years. Controls were
      102 hospital volunteers (42 males and 60 females) including 42 patients with
      miscellaneous diseases, aged 15 to 75 years. Gastric atrophy was evaluated with
      serum pepsinogens (PG1<70 ng/ml and PG1/PG2<3). Polymorphisms of PTPN11 at intron
      3 (rs2301756) and intron10 (rs12229892) were genotyped with PCR with confronting
      two-pair primers (PCR-CTPP). Anti-cagA IgG antibody was detected in 93.7% of
      cases and 77.5% in controls. Gastric atrophy was observed in 24.2% of the PUD
      patients and 33.3% in the controls. The A allele at intron 3 was completely
      linked to the G allele at intron 10. The age, sex, and group (cases and controls)
      adjusted odds ratio of gastric atrophy was 0.18 (95% confidence interval, 0.04
      0.86) for intron 3 GG genotype relative to AA genotype. Since the finding was
      opposite to that among Japanese, the H. pylori strains and/or lifestyle in
      Uzbekistan might modify the association.

PMID- 18712963
TI  - Knowledge and behavior regarding breast cancer screening among female teachers in
      Selangor, Malaysia.
AB  - A cross-sectional study was carried out to determine the knowledge and practices
      of 425 female secondary school teachers from 20 selected secondary schools in
      Selangor, Malaysia on breast cancer screening (BCS). A self-administered,
      structured questionnaire was used for data collection. This study showed moderate
      to low knowledge on breast cancer (BC) and BCS among teachers. Only 19%, 25% and
      13.6% eligible women performed breast self-examination (BSE), clinical breast
      examination (CBE) and mammography respectively, on a regular basis. Level of
      breast cancer knowledge was significantly associated with BSE (p<0.001). Having
      heard/ read about BCS, and regular visit with a physician were associated with
      BCS behaviors (P<0.05). There was no association between BCS behaviors (P>0.05)
      and age, family history of breast cancer, marital status or having health
      insurance. Efforts are needed to increase knowledge and remove misconceptions
      about breast cancer and screening practices among Malaysian women.

PMID- 18712964
TI  - Malignant lymphomas in Pakistan according to the WHO classification of lymphoid
      neoplasms.
AB  - OBJECTIVE: To determine the spectrum of malignant lymphomas in our set up,
      according to the WHO classification. METHODS: All the cases diagnosed as
      malignant lymphoma, during the year 2005, were retrieved from the institution
      based tumour registry record and classified according to WHO criteria depending
      on the immunohistochemical results of a panel of lymphoma markers. RESULTS: The
      male to female ratio was 2.5:1 for almost all types of malignant lymphomas. The
      age range was 3 to 80 years. The frequency of Hodgkin's lymphoma, Burkitt's
      lymphoma and lymphoblastic lymphoma were higher amongst the children, whereas
      follicular lymphomas, mantle cell lymphoma and CLL/SLL were more frequently
      reported in 5th, 6th and 7th decades. Of the total cases 62% were nodal and 38%
      extranodal (majority in the GI tract). Non Hodgkin's lymphoma was more (73%)
      frequent than Hodgkin's disease. Mixed cellularity and nodular sclerosis were the
      main histological variants of Hodgkin's disease. CONCLUSIONS:
      Immunohistochemistry is not very frequently used in our set up and also at very
      few other centres. Therefore, its application should be encouraged to raise the
      quality of data on lymphoid neoplasms and contribute to their control.

PMID- 18712965
TI  - Real-time PCR assay for rapid detection of GSTM1 polymorphism in nasopharyngeal
      carcinoma patients.
AB  - Nasopharyngeal carcinoma (NPC) is a common public health problem in Thailand.
      Glutathione S-transferase M1 gene deletion (GSTM1 null genotype) carriers have
      been reported to be at increased risk and therefore this parameter is a potential
      marker for screening of NPC high-risk individuals. However, the conventional
      polymerase chain reaction (C-PCR) assay commonly used for GSTM1 null genotype
      detection is not suitable for mass screening since it is inconvenient, time
      consuming and unsafe due to the use of a toxic chemical. Currently, real-time PCR
      (R-PCR) assay is recommended for quicker and safer detection of various genetic
      polymorphisms. The aim of this study was to develop a SYBR green I R-PCR assay
      combined with melting curve analysis for GSTM1 polymorphism detection in Thai NPC
      patients. The results were compared to those from the C-PCR assay using DNA
      samples from peripheral blood leukocytes of 120 Thai NPC patients. The
      frequencies of GSTM1 polymorphism detected by the R-PCR and the C-PCR were the
      same. Forty-eight individuals that were GSTM1+ in the R-PCR assay showed 2 peaks
      with melting points of 82.5 and 87.5 that correlated with the appearance of 2 DNA
      bands in the C-PCR assay (i.e., one for GSTM1 at 215 base pairs (bp) and one for
      ?-globin at 268 bp). By contrast, 72 individuals that were GSTM1?- in the R-PCR
      assay showed 1 peak with a melting point of 87.5C that correlated with the
      appearance of 1 DNA band for -globin at 268 bp in the C-PCR assay. The R-PCR
      assay using SYBR Green I and melting curve analysis for GSTM1 polymorphism
      detection was as reliable as C-PCR assay but was quicker and safer and more
      amenable to large scale screening in Thai NPC cases.

PMID- 18712966
TI  - Factors related to starting and continuing smoking among senior high school boys
      in Fukuoka, Japan.
AB  - The purpose of this study was to identify factors that influence starting and
      quitting smoking among Japanese male adolescents aged 15-18. Two thousand and
      twelve senior high school boys in Fukuoka City, Japan, answered unsigned self
      administrated anonymous questionnaires in July 2001. Odds ratios (ORs) and their
      95 % confidence intervals (CIs) were computed to assess the strength of
      associations between students' smoking status and alcohol consumption habits.
      Additionally, the link between a students' smoking status and parental influence
      (parental smoking) was also assessed. Approximately 90% of the students, both
      current and ex-smokers, had ever smoked prior to senior high school while 77% of
      the students (smokers and non-smokers) had the experience of drinking alcohol
      prior to admission to senior high school. After adjustment for school year (i.e.,
      freshman, sophomore, junior, senior), academic education level, after-school club
      activities, time of first drinking experience and the frequency of drinking,
      there was a significant increased risk to become a smoker when one parent was a
      smoker (OR = 1.67, 95% CI = 1.18-2.37) or when both parents were smokers (OR =
      2.94, 95% CI = 1.66-5.18) compared to both parents being non-smokers. The
      consumption of alcohol prior to entering senior high school was significantly
      associated with more than 2.5-fold greater risk for the onset of smoking when
      compared to the risk of becoming a smoker when alcohol consumption started after
      entering senior high school. An increased frequency of drinking was also
      associated with starting smoking (OR =14.00, 95% CI = 8.08-24.26; 2-3 times/week
      vs. never). Similarly, an increase in drinking frequency resulted in less
      likelihood of smoking cessation. For instance, the data showed that, the subjects
      were 1/3 less likely to quit smoking. Paternal smoking had a significant impact
      on whether or not a child would quit smoking (OR = 0.55, 95% CI = 0.38-0.81) as
      compared to a child that had paternal and maternal non-smokers. This study
      suggested that drinking habits started earlier than smoking habits among
      adolescents. Many students had already experienced drinking before admission to
      senior high school, while the experience of smoking mostly typically started
      after admission to high school. These data show the urgency of developing anti
      smoking educational programs that could be developed and introduced prior to
      admission to high school.

PMID- 18712967
TI  - Secondhand smoke exposure among nonsmoking adults in Seoul, Korea.
AB  - Despite having one of the highest smoking rates among men, information about
      secondhand smoke (SHS) exposure among Korean adults is lacking. This study
      describes SHS exposure among Korean men and women. The results were derived from
      a population-based, cross-sectional telephone survey conducted with 332 adult
      nonsmokers in Seoul. Sixty-eight percent of nonsmokers were exposed to SHS during
      a typical day. Exposure was most common in locations other than home and work,
      where 57% of respondents were exposed, compared to 26% at home and 25% at work.
      However, among those exposed, the greatest dose of exposure occurred at work (9
      cigarettes/day), followed by at home (6 cigarettes/day). Men were more likely to
      be exposed to SHS at work than women. For men, lack of home smoking bans and
      strong belief in traditional Korean values were independently associated with SHS
      exposure in any location. For women, younger age, family members' smoking (non
      spouse), and having fewer sources of anti-SHS messages were independently
      associated with SHS exposure anywhere. The results highlight the need for strong,
      comprehensive SHS control measures, such as a complete ban of smoking in all
      workplaces and public places, as well as public health campaigns to promote home
      smoking bans and non-smoking norms.

PMID- 18712968
TI  - Prevalence of high grade squamous intraepithelial lesion (HSIL) and invasive
      cervical cancer in patients with low grade squamous intraepithelial lesion (LSIL)
      at cervical pap smear.
AB  - OBJECTIVE: To assess the prevalence and factors associated with a histologic
      diagnosis of high grade squamous intraepithelial lesion (HSIL) and invasive
      cervical cancer in patients with low grade squamous intraepithelial lesion (LSIL)
      cervical pap smear findings. METHODS: Medical records (including cytology
      reports, colposcopic impression, and pathologic results from cervical biopsy,
      endocervical curetting, cervical conization or hysterectomy) of 226 women with
      LSIL from conventional cervical pap smears during January 2001 to December 2005,
      who subsequently underwent colposcopic evaluation at our institution, were
      reviewed. RESULTS: Mean age of the patients was 39.0 years. The incidences of
      LSIL, HSIL, microinvasive cervical cancer were 58.8%, 15.0%, 1.3% respectively.
      No associations were found between age, parity, contraception, anti-HIV or
      menstrual status and the detection of HSIL/invasive cervical cancer. CONCLUSION:
      Approximately 16.3 % of LSIL pap smear cases turn out to be HSIL or invasive
      cervical cancer from histologic diagnosis.

PMID- 18712969
TI  - New methods of handling cases of unknown age in cancer registry data.
AB  - OBJECTIVE: The essential assumption of random missing age behind the
      "conventional method" of handling cancer patients of unknown age does not often
      hold. This article is to introduce four alternative methods based on more
      acceptable assumptions. METHODS: More cases with unknown age are allocated to the
      older age-groups in all the new methods. In the "weighting method," cases of
      unknown age are distributed according to distribution of cases of known age,
      whereas in the "last-group method," all of them are added to the oldest age
      group. In the "progressive method," unknown-age cases are added to the age-groups
      above 60 progressively (weighting=1/63, 2/63, 4/63, 8/63, 16/63, and 32/63),
      whereas in the "additive method," they are allocated to the age-groups above 60
      additively (weighting=1/21, 2/21, 3/21, 4/21, 5/21, and 6/21). Data were from the
      Cancer in Five Continent database, vol. VIII. RESULTS: Age-standardized rates for
      "All sites" in Zaragoza (Spain), Cali (Colombia), Algiers (Algeria), and Gambia
      showed that results by all the methods differed, the magnitude ranging from 0.1
      to 3.1% depending on the method, registry, sex, and the defined last age-group.
      CONCLUSION: Conventional and weighting methods are not based on acceptable
      assumptions. The last-group method is not stable because it depends on the
      defined age-group as last (65+, 75+ or 85+). Both progressive and additive
      methods have more acceptable assumptions. The progressive method is preferable
      above all others because it can produce an age-specific curve with the expected
      exponential increase.

PMID- 18712970
TI  - Prevalence of oral pre-malignant and malignant lesions at a tertiary level
      hospital in Allahabad, India.
AB  - OBJECTIVE: In a previous article, we reported the prevalence rates of oral
      mucosal lesions in this hospital from 1990-2001. This study was planned to study
      the spectrum of potentially malignant and malignant oral lesions in Allahabad,
      North India in the subsequent years till 2007 and to assess change in pattern of
      prevalence, if any. MATERIALS AND METHODS: This is a single institutional
      retrospective study in and around Allahabad from 1990 to 2007. Data was collected
      year wise with reference to age, sex, site involved and histopathological
      findings. RESULTS: 1,151 oral biopsies were reviewed. Of these, 365 biopsies were
      benign, 344 were potentially malignant and 442 were malignant. The buccal mucosa
      was the most frequently involved site in benign and premalignant lesions, however
      in malignant lesions, the tongue was most common site. Oral submucous fibrosis
      constituted the highest number of patients in premalignant group, while in
      malignant group, squamous cell carcinoma was most prevalent. CONCLUSION: This
      study showed that potentially malignant and malignant oral lesions were
      widespread in the patients visiting the hospital in this region.

PMID- 18712971
TI  - Trends in the brain cancer incidence in India.
AB  - Trends in cancers of the central nervous system in both sexes in five Indian
      population based cancer registries (Mumbai, Chennai, Bangalore, Delhi & Bhopal)
      were evaluated over a period of the last two decades. For this purpose we applied
      a model that fits the data is the logarithm of Y=ABx which represents a Linear
      Regression model. This approach revealed an increasing trend in cancers of
      nervous system in both sexes throughout the entire period of observation in
      almost all registries. As CNS cancers are increasing, analytic epidemiological
      studies should be planned in a near future on a priority basis to understand the
      etiology of these cancers in depth.

PMID- 18712972
TI  - Geriatric cancers in India: an epidemiological and demographic overview.
AB  - This article provides an overview of aspects of the burden of cancer in the
      elderly, in India highlighting certain demographic and epidemiological data. In
      India the normal retirement age is 60 years, so the definition of the elderly, in
      India is considered above the age of 60 years. Information on the aging of the
      Indian population is based on various census figures, cancer incidence figures
      are taken from Mumbai registry data. Men and women aged > or = 60 years are at
      high risk for major cancers. Men have a risk 15 times greater risk and in women 8
      times greater risk than the persons having age < 60 years. Lung and prostate
      cancers are most prominent cancer in men having age > or = 60 years while in
      women breast is the leading site followed by cervix and ovary in the same age
      group. Demographic and epidemiologic data characterize the aging / cancer
      interface. The changing demographic structures underscore the current incidence
      imperative for elderly; suggesting a starting demand will be made in the future
      requiring physician's abilities and skills to meet these needs.

PMID- 18712973
TI  - Outcome of breast cancer in Iran: a study of Tehran Cancer Registry data.
AB  - BACKGROUND: Breast Cancer is the second most common cancer among Iranian women.
      This study was conducted to define the outcome of breast cancer which had been
      registered by Tehran Cancer Registry. METHODS: All Tehranian breast cancer which
      registered from 1998 to 2001 was selected; the repeated cases were excluded
      according to their common name, family name, and Father's name. A simple data
      collection form was used to complete the demographic and diagnostic time and
      survival situation of the cases by five educated technicians with using phone
      interviews with patients or their families. All data were entered in Access file
      and then exported to SPSS-11.5, for descriptive and analytic analysis, p value
      was significant under 0.05. Since there were some cases had not phone number or
      the phone numbers were not accessible; 360 cases were selected with Simple Random
      Sampling and their hospital files were reviewed to complete the demographic and
      location situations data. Kaplan- Meier regression model was used for computing
      the survival. RESULTS: Of the 7098 records, 4416 records were interviewed by
      phone. This phone interviews were succeeded among 2358 cases; Tehranian and other
      cities were defined in 986 and 1372 records respectively. The Tehranian cases
      were estimated 36.9% (CI95%: 31.9%-41.8%). The mean age of patients was 51.3+/
      12.5, 31.4% of them was under 40 years old, the incidence rate of breast cancer
      in 100,000 women was estimated 17.09 CI95% (15.67-18.50). Infiltrating duct
      carcinoma was the most morphology (68.4%). Right, left, and both breast
      involvement were seen in 48.6% CI95% (43.4%-53.8%), 46.1% CI95 %( 41.0%-51.2%),
      0.3% CI95%(0.1%-0.5%) respectively. The tumor size over 2 centimeters was seen in
      63.6% of cases at diagnostic time. Lymphadenopathy and metastasis were seen in
      48.3% CI95% (43.1%-53.5%), and 19.7% CI95% (15.6%-23.8%) of cases. The median
      survival was 5.0 years CI95% (4.9 years-5.1 years). CONCLUSION: This
      retrospective survival study was shown the seven years follow up from 1998 to
      2005, women which were diagnosed in 1998, 1999, 2000, and 2001; 55.9%, 61.4%,
      60.3%, 66% were alive respectively. Interventional projects for increasing the
      survival rate, early detection, and effective treatment of breast cancer were
      recommended.

PMID- 18712974
TI  - Aspirin intake suppresses MMC-induced genotoxicity in mice.
AB  - The genotoxicity induced by mitomycin C (MMC) was found to be decreased by
      aspirin on alkaline single cell gel electrophoresis (SCG) assay in multiple
      organs of mice. Aspirin at doses of 0.5, 5 and 50 mg/kg and MMC at 2 mg/kg were
      administered and then liver, lung, kidney, spleen, colon and bone marrow were
      sampled after 3 h. Significant protective effects of aspirin against MMC-induced
      genotoxicity was observed in all but the bone marrow, where no change was
      evident. The results suggest that the radical scavenging ability of aspirin
      prevents danage by MMC-induced reactive oxygen species (ROS) in multiple organs.

PMID- 18712975
TI  - Endometrial adenocarcinoma in young Thai women.
AB  - OBJECTIVE: To evaluate the clinicopathological characteristics and survival
      analysis in endometrial adenocarcinoma women younger than the age of 40 years
      compare to older women. METHODS: Medical records of 423 endometrial
      adenocarcinoma patients who received primary surgical treatment at King
      Chulalongkorn Memorial Hospital during 1996-2005 were reviewed. The patients were
      divided into two groups; 40 years of age or younger (group A, 42 patients) and
      older than 40 years (group B, 381 patients). RESULTS: Up to 10% (42/423) of
      endometrial adenocarcinoma patients were younger than the age of 40 years. The
      higher incidence of nulliparous and obesity (BMI > 30 kg/m2) was significantly
      demonstrated in group A (81%/34.1% and 52.4%/25.2%, respectively). However,
      obesity was an only independent factor in multivariate analysis. No significant
      difference in surgical stage distribution and the other pathologic
      characteristics was demonstrated between both groups. However, poor histologic
      grade (grade 3) and deep myometrial invasion (myometrial invasion more than 50%)
      tended to be found more frequent in the patients older than the age of 40 years,
      although there was no statistical significance (16% versus 4.7% and 31% versus
      14.3%, respectively). Moreover, synchronous ovarian cancer seemed to be higher in
      young patients (7.1% and 2.9%, p > .05). Median time to follow was 63 months
      (range 0-145 months). Five years disease free survival and 5 years overall
      survival were 87.3% and 92.4% in group A versus 83.8% and 88.0% in group B
      without statistical significance between both groups. CONCLUSIONS: Obesity was
      the only independent factor associated with endometrial adenocarcinoma in young
      patients. Distribution of the surgical stage and the other pathologic
      characteristics were similar between both groups without survival benefit in
      young patients.

PMID- 18712976
TI  - hTR RNA component as a marker of cellular proliferation in oral lichen planus.
AB  - Previously, we have shown that the telomerase RNA component hTR is highly
      expressed in the epithelium of non-dysplastic Oral Lichen Planus (OLP) lesions
      (11). We concluded that it is possible that this high expression might be related
      to the increased cellular proliferation seen in OLP rather than being an
      indicator of potential malignant transformation. In the present study, and in
      order to confirm our finding in the previous study that hTR might be a marker for
      cellular proliferation in OLP, we analysed OLP biopsies known to be positive for
      RNA component of Telomerase (hTR) for the expression of Ki-67 as a marker for
      cellular proliferation. Fourteen OLP tissue biopsies known to be positive for
      telomerase RNA component hTR, were investigated using an immunohistochemical
      approach to determine the rate of cellular proliferation in OLP, looking at the
      expression of Ki-67 protein as a marker for cellular proliferation. A
      statistically significant increase was found between Ki-67 expression in OLP in
      comparison to normal control buccal mucosa samples. The expression of hTR
      component in OLP might thus be a marker for cellular proliferation.

PMID- 18712977
TI  - Methylthioadenosine phosphorylase expression in cutaneous squamous cell
      carcinoma.
AB  - The methylthioadenosine phosphorylase (MTAP) gene is a tumour suppressor gene,
      located on chromosome 9p21, 100 kb telomeric of the p15 and p16 genes, which are
      often deleted in tumor cells. The role of MTAP protein expression in the genesis
      of cutaneous squamous cell carcinoma (SCC) is currently not known. In a previous
      study we have shown the frequent occurrence of allelic imbalance/loss of
      heterozygosity (AI/LOH) in cutaneous SCCs using AI/LOH markers flanking the p15,
      p16, and MTAP genes and demonstrated reduction in p15 and p16 protein expression
      in comparison to normal human skin. The present study is a continuation to our
      previous studies, aimed at determining possible roles played by MTAP protein
      expression in the genesis of cutaneous SCC. The expression of MTAP protein was
      detected using immunohistochemical approach in 109 micro array cutaneous SCC and
      20 normal human skin tissue samples. The expression of MTAP was not significantly
      different in the cutaneous SCC cases as compared with normal human skin. This may
      indicate that MTAP protein expression does not contribute to the genesis of
      cutaneous SCC.

PMID- 18712978
TI  - Lack of influence of cyclooxygenese-2 expression in hepatocellular carcinomas on
      patient survival.
AB  - Recent studies suggest that cyclooxygenese-2 (COX-2) enzyme activation may play a
      role in hepatocarcinogenesis. However, the clinical significance of COX-2
      expression in hepatocellular carcinoma (HCC) remains obscure. This study
      evaluated COX-2 expression in hepatitis B and hepatitis C virus related HCC and
      in HCC patients with an unknown etiology. Liver tissue samples of 31 patients
      with HCC (27 men and 4 women; age range, 48-75 years) were analyzed. COX-2
      expression was evaluated by immunohistochemically in the tumor tissues. Patient
      data including age, sex, Child score, stage, grade of the tumor and survival were
      analyzed. Of these patients 19 were positive for hepatitis B virus (HBV), 6 were
      positive for hepatitis C virus (HCV) and 6 patients were negative for all viral
      markers and other etiologic factors. COX-2 staining were evaluated in 2 groups
      (group 1: COX-2 expression less than 25% (grades 1-2 COX-2 expression), and group
      2: Cox-2 expression 25% or more (grades 3-5 COX-2 expression). COX-2 expression
      was shown in all HCC samples with positive or negative viral markers. No
      difference was found between degree of COX-2 expression and the etiology of HCC.
      COX-2 expression was not correlated with number of lesion or stage of the disease
      or grade of the tumor. COX-2 expression was not related with Child score of the
      patients. Median survival of all patients was 32 months. Median survival of
      patients did not differ according to patient's viral marker status. No difference
      was observed in median survival of patients in group 1 and 2. As a result, COX-2
      system seem to be shared part in hepatocarcinogenesis regardless factors that
      initiate the disease. Although COX-2 expression appears to be independent of
      disease's characteristics', treatments that target this system appear to be
      feasible in the management of HCC.

PMID- 18712979
TI  - Gastric and colo-rectal cancer mortality in Viet Nam in the years 2005-2006.
AB  - BACKGROUND: The International Collaborative Epidemiological Study of Host and
      Environmental Factors for Stomach and Colorectal Cancers in Southeast Asian
      Countries (SEACs) has been conducted in Viet Nam from 2003 to 2008 on a case
      control basis. For further effective primary prevention, we examined gastric and
      colorectal cancer mortality nationwide in eight regions of Viet Nam in 2005-06.
      METHODS: Both demographic data and lists of all deaths in 2005-06 were obtained
      from all 10,769 commune health stations in Viet Nam. Five indicators included
      name, age, sex, date of death and cause of death was collected for each case. We
      selected only communes having the list of deaths with clear cause for each case
      and crude mortality rate for all causes from 300-600/100,000 as published by the
      Ministry of Health for a reasonable accuracy and completeness. Obtained data for
      all causes, all cancers, stomach and colorectal cancer deaths as well as
      demographic information were processed using Excel software and exported to STATA
      8.0 for estimation of world age-standardized cancer mortality rates per 100,000.
      RESULTS: Data were available for 1,246 gastric cases, (819 male and 427 female)
      with age-standardized mortality rates from 12.7 to 31.3 per 100,000 in males and
      from 5.9 to 10.3 per 100,000 in females in the 8 regions of the country. For
      colorectal cancers, 542 cases (268 male and 274 female) gave mortality rates from
      4.0 to 11.3 per 100,000 in males and from 3.0 to 7.8 per 100,000 in females.
      DISCUSSION: Stomach cancer mortality in males in the region of North East in the
      North Viet Nam (2005-06) was higher than that in Japan (2002) (31.3 versus 28.7
      per 100,000) while colorectal cancer in Viet Nam was lower. While prevalence of
      Helicobacter pyloris infection in Viet Nam was from 70-75% in both males and
      females, the stomach cancer rate in males was significantly higher than in
      females, 31.3 versus 6.8 per 100,000, suggesting an influence of other
      environmental risk factors. Whether protective factors are operating against
      colorectal cancer in Viet Nam now needs to be explored.

PMID- 18712980
TI  - Factors influencing in-hospital length of stay and mortality in cancer patients
      suffering from febrile neutropenia.
AB  - INTRODUCTION: Febrile neutropenia (FN) is a major complication of chemotherapy,
      costly in terms of morbidity, mortality and associated financial expenditure. The
      present study was conducted with the goal of highlighting FN as a serious problem
      in Pakistan, with the longer term objective of improved cancer survival,
      reduction in length of stay (LOS) in hospital, morbidity, mortality and costs in
      our existing developing country scenario. METHODS: A cross-sectional descriptive
      study was conducted on patients, > or =18 years, admitted with FN as a
      consequence of chemotherapy at a referral hospital in Karachi from 1st September
      2006 to 30th April 2007. RESULTS: A total of 80 patients [43 (53.8%) males and 37
      (46.2%) females] were selected. The mean age was 47.4 (SD +/-16.6; range 18-79)
      years. Sixty eight patients (86%) were < or = 65 years, 50% were < or = 50 years.
      Overall, inhospital mortality was 11%; 4% for patients on granulocyte colony
      stimulating factor (G-CSF) prophylaxis as against 20% for those without. The
      cause of death was either pneumonia or septic shock. Mean LOS was 7.53 (SD +/
      3.8; range 2-17) days. Hematological malignancies, older age, severity of
      dehydration, pneumonia and culture positivity were significantly associated with
      LOS and death. Those above 50 years of age were 1.5 times as likely to be
      hospitalized longer and > three times as likely to die. Bacteremia conferred a 5
      fold and pneumonia an 8-fold increase in the risk of death. CONCLUSION: The
      results of this study indicate that age, vital instability, dehydration, high
      creatinine, culture positivity and hematological malignancies are high risk
      factors in chemotherapy induced FN. Identification of FN risk factors with poor
      outcomes may help in devising protocols for modified dosage or including GCFs
      initially. This may help reduce the cost of cancer care as well as mortality and
      morbidity. Prospective studies of FN in multiple centers in Pakistan may be
      beneficial in evaluating these risk factors further.

PMID- 18712981
TI  - Association between risk of breast cancer and fertility factors--a latent
      variable approach.
AB  - BACKGROUND: Breast cancer is the most common malignant tumor in females. Many
      studies have been carried out in order to assess the reproductive risk factors.
      Particular attention has focused on information regarding fertility, including
      breastfeeding, age at first birth and number of live births. These factors are
      highly correlated with each other. The objective of this study was to employ
      latent variables to reduce the confounding effect of this correlation with a
      logistic regression analysis. METHODS: The investigation drew upon results from a
      dataset belonged to a hospital based case-control study covering 303 breast
      cancer patients and 303 hospital controls. Data were collected through interview
      and reproductive variables included age at first full-term pregnancy and live
      birth, number of pregnancies and live births, and total length of breast feeding.
      Latent variables were generated using factor analysis and principal components
      analysis. RESULTS: The study revealed that for both latent variable approaches
      the odds ratios of two latent variables significantly indicated a protective
      impact of number of pregnancy and live birth and breastfeeding and a prognostic
      relation with age at first pregnancy or live birth. CONCLUSION: The findings
      suggest that breastfeeding and decreasing age at first live birth have protective
      influences on breast cancer risk. Also using statistical model with latent
      variables in the presence of collinear data leads to reliable results.

PMID- 18712982
TI  - Lack of chronic oral toxicity of chemopreventive bovine lactoferrin in F344/DuCrj
      rats.
AB  - Studies were undertaken to determine whether bovine lactoferrin (bLF) and related
      compounds, shown to prevent carcinogenesis in the colon and other organs in rats,
      have any toxic effects in long-term feeding studies. In experiment I, male
      F344/DuCrj rats received a basal diet containing 0.2% bLF for 40 weeks. No
      adverse findings were noted, furthermore, serum triglyceride level was
      significantly decreased to 72% of the control level, suggesting preventive
      effects against the metabolic syndrome. In experiment II, male and female
      F344/DuCrj rats were fed a basal diet containing 0.02, 0.2, 2.0 and 5.0% bLF,
      2.0% bLF hydrolysate (bLF-H) or 0.1% lactoferricin (LFcin), a peptide derived
      from bLF, for 60 weeks in males and 65 weeks in females. No toxicological
      effects, including carcinogenicity, were evident in either sex. The results of
      the studies provide subjective support for safety of clinical studies of bLF for
      supplement use.

PMID- 18712983
TI  - Survival rates and prognosis of gastric cancer using an actuarial life-table
      method.
AB  - BACKGROUND AND AIMS: The aim of this study was to calculate survival rates and
      analyze patterns of survival in gastric cancer. METHODS: A total number of 746
      patients with gastric cancer registered in the Cancer Registry Center of Research
      Center of Gastroenterology and Liver Disease of Shahid Beheshti University of
      Medical Sciences, Iran, from Dec 21, 2001 to Dec 21, 2006 were investigated. 1-
      to 5-year survival rates were estimated using life-table method and compared by
      Wilcoxon (Gehan) test. P<0.05 was considered as statistically significant. All
      calculations were carried out with SPSS (version 13.0) statistical software.
      RESULTS: There were 530 male patients with a mean age of 60.5+/-12.6 years and
      216 females with a mean age of 57.5+/-13.5 years. Of the total, 454 died and 285
      were censored during the investigation. The median survival time was 24.2 months
      and survival rates at one, two, third, fourth and five years after diagnosis were
      73.6, 50.2, 40.6, 33.2 and 29.7%, respectively. Stages of tumor, histology grade,
      histologic type of cancer, tumor size, age at diagnosis and surgery approach were
      independent prognostic factors . However, variables such as sex (P=.533), body
      mass index (P=.214), ethnicity (P=.092), and level of education (P=.762) did not
      shown significant effects on survival. CONCLUSION: Early detection of patients at
      lower age and with primary stages and grades of tumor is important to increase
      patient's life expectancy.

PMID- 18712984
TI  - Assessment of confounding and interaction using the mantel-haenszel risk
      estimation method.
AB  - The association between an exposure of interest (risk factor) and a disease may
      be confounded by the action of other separate factors as well as by interactions
      between risk factors exerting an impact. Crude measures of effect may be
      misleading in such situations. Levels of the potential confounding factor could
      be estimated using stratified analysis. Uniformity of the stratum-specific effect
      estimates can be assessed by performing chi-square tests for heterogeneity. If
      the effect is uniform across strata, we can calculate a pooled adjusted summary
      estimate of the effect using the Mantel-Haenzel (M-H) method. Confidence
      intervals for the adjusted estimate and the M-H chi-square test are calculated to
      assess the significance. If the effect is not uniform (presence of interaction),
      we report stratum-specific estimates, confidence intervals and chi-square for
      each estimate. In the present paper, assessment of the level of confounding and
      interaction between risk factors are illustrated using a case-control study of
      lung cancer conducted at the Regional Cancer Centre, Trivandrum.

PMID- 18712985
TI  - Cancer in East Azerbaijan, Iran: results of a population-based cancer registry.
AB  - BACKGROUND AND AIMS: Regardless of the fact that cancers of GI tract have been
      reported to be the most common fatal neoplasms in East Azerbaijan, there is a
      serious lack of population-based studies in this region. METHODS: A comprehensive
      search was therefore undertaken to prospectively register all cases of cancer
      occurring in the province during March 2006-2007. Diagnosis of cancer was based
      on histopathology of primary lesions in 84.0% of cases, clinical investigation
      and ultrasound in 7.2%, only clinical investigation in 5.4%, and histology of
      metastasis in 2.9. Less than 1% were based on cytology and death certificates in
      one official year. RESULTS: A total of 4,922 cancers (mean age 60.2+18.13 years)
      were diagnosed during this population-based study. Of these, 56.8% (2114) were in
      males. ASRs for all cancers in males and females were 164.3 and 130.6
      respectively. The top five sites for cancer in males (excluding skin cancer)
      according to the calculated ASR (world) were stomach (26.0), bladder (15.7),
      esophagus (12.4), colon and rectum (11.6) and blood (10.8); in females, they were
      breast (23.5), esophagus (11.7), stomach (11.6), colon and rectum (9.7) and
      nervous system (5.5). CONCLUSION: This first comprehensive report on cancer
      incidence in East Azerbaijan, documents particularly high incidence rates for
      esophageal and gastric cancer across the sexes.

PMID- 18712986
TI  - Epidemiology of ovarian cancer in Kyrgyzstan women of reproductive age.
AB  - The purpose of the present study was to assess the ovarian cancer incidence rate
      among women of reproductive age in Kyrgyzstan. Sources of data were records of
      all patients who were first diagnosed as suffering from ovarian cancer at
      reproductive age (15-49) during the period 1999-2006. Descriptive and analytical
      methods of onco-epidemiology were applied. It was established that the ovarian
      cancer incidence among general female population of reproductive age equaled
      4.3+/-0.3 per 100,000 population. Incidence rate was increasing in dynamics.
      Average age of patients in this category was 37.9+/-0.5. Analysis of age
      indicators demonstrated that incidence rate was higher within later reproductive
      age (40-49) at 11.2+/-0.60/0000. Incidence among the two main ethnic population
      groups was analyzed: Kyrgyz and Russian. Whereas rates appeared to be increasing
      in the former, the latter demonstrated paradoxical decrease.

PMID- 18712987
TI  - Longitudinal study of smoking progression in Chinese and Vietnamese American
      adolescents.
AB  - The use of tobacco remains a significant public health concern among Asian
      American (AA) adolescents. Understanding the factors that affect smoking
      progression among Chinese and Vietnamese adolescents in particular, may help in
      illuminating potential interventions that can be implemented to maximize scarce
      programming and resources. This study is a longitudinal cohort study with data
      collected in California via telephone over a two-year period. 1,270 Chinese and
      Vietnamese American adolescents were recruited via telephone listings from one
      southern and four northern California counties. Main outcomes were smoking
      susceptibility and change in smoking status. Examination of these adolescents
      indicated that in both groups: boys were more likely than girls to become
      susceptible to smoking, risk behaviors were associated with becoming smokers,
      having been susceptible at baseline was associated with susceptibility and
      smoking at follow-up, and the influence of friends was a predictor of
      susceptibility and smoking.

PMID- 18712989
TI  - Comparison of mediterranean, Western and Japanese diets and some recommendations.
AB  - During the past thousands of years, food systems, and thus human diets, have been
      and are shaped by climate, terrain, seasons, location, culture, and technology.
      In this context, many types of diet patterns have emerged. Nowadays, numerous
      epidemiological studies are being conducted in many countries in order to find
      relationships between empirically identified dietary factors and the occurrence
      of illnesses. Today, some dietary patterns are described as healthy eating models
      while others are generally qualified as unhealthy.

PMID- 18712988
TI  - Antioxidant intake and status, and oxidative stress in relation to breast cancer
      risk: a case-control study.
AB  - A case control study was carried out to investigate associations between breast
      cancer risk, antioxidant status and oxidative stress among women in Klang Valley
      and Selangor. A total of 57 newly diagnosed cases aged 30 to 66 years old
      participated and were matched for age and ethnicity with 139 controls with no
      diagnosis of cancer or other chronic diseases. An interview based questionnaire
      designed to collect information on demographic and socioeconomic status, as well
      as reproductive, medical and dietary history was used. Anthropometric
      measurements including weight, height, waist and hip circumference were made and
      a 10 ml fasting venous blood sample was taken for glucose testing and analysis of
      plasma vitamin antioxidants and malondialdehyde. Hair and toenail samples were
      taken for selenium analysis. Results showed that the mean intake of vitamin A,
      vitamin E and selenium among cases (606.8 +/- 334.8 microg/d, 6.1 +/- 2.4 g/d,
      56.9 +/- 16.2 microg/d) was lower than controls (724.7 +/- 414 microg/day, 6.9 +/
      3.0 g/d, 60.8 +/- 17.5 microg/d, respectively) (p<0.05 for all parameters). A
      similar trend was noted for plasma vitamin A and E and also selenium in hair and
      toenails. Poor antioxidant status as indicated by low plasma vitamin A (<284.3
      microg/l or <366.3 microg/l) increased risk of breast cancer by approximately two
      fold, whilst low plasma vitamin E (<2.5 mg/dl, <2.8 mg/dl and <3.1 mg/dl)
      increased the risk by two to three fold [Adjusted OR 2.97 (95% CI 1.38-3.48),
      2.32 (95% CI 1.07-2.41) and 2.12 (95% CI 1.00-4.21)]. Cases had a greater level
      of malondialdehyde 4.4 +/- 1.1 mmol/g protein), an indicator of oxidative stress,
      as compared to controls (3.2 +/- 1.7 mmol/g protein) (p<0.05). A high level of
      MDA (> or = 4.8 mmol/g protein) was associated with breast cancer [Adjusted OR
      6.82 (95% CI 1.95-23.9)]. It is concluded that a poor antioxidant status and high
      oxidative stress are associated with breast cancer risk. Thus, it is essential
      for Malaysian women to obtain a good antioxidant status by consuming a diet rich
      in vitamins A and E as well as selenium and adopt healthy behaviour to reduce
      oxidative stress in order to prevent breast cancer.

PMID- 18712990
TI  - Community participatory approach: an important managerial role in cancer control.
AB  - Despite the mountain of information generated by researchers, the cancer problem
      has not significantly declined and perhaps in certain situations it is gradually
      increasing, affecting those who are previously at low risk. There is a tendency
      to believe that positive outcomes can always be expected once intervention
      activities, like exercise promotion, are carried out, but practical experience
      gives rise to serious doubt. A greater understanding of the biological mechanisms
      operating in the physical activity, cancer relation, complete measurement of
      physical activity through a subject's life, assessment of all potential
      confounders and association modifiers are needed to confirm a protective role of
      physical activity in cancer development and allow specific exercise prescriptions
      for community-based prevention in particular cancer sites. Furthermore, the most
      important impetus of any community intervention approach should be oriented in
      the form of 'from people to the people'. More emphasis needs to be placed on
      effective management and parameters for assessment of management success.

PMID- 18712991
TI  - Epidemiologic patterns of primary brain tumors in Iran.
AB  - There appear to be some differences between the patterns of brain tumor
      epidemiology in Iran and western countries. Thus, the prevalence of glioma was
      earlier estimated to be about 45% of all brain tumors, somewhat low in comparison
      to the western reports at that time, but almost the same as in Southeast Asian
      countries. A similar low figure was also obtained more recently indicating that
      the earlier estimate was not simply due to the lack of medical facilities
      resulting in under-reporting of this particularly malignant form of cancer. There
      may also be differences regarding incidences of central nervous system (CNS)
      tumors in females between Iran and Western countries. Clearly this is an area
      which deserves epidemiological research.

PMID- 18712992
TI  - Primary non-Hodgkin,s lymphoma of the uterine cervix.
AB  - Primary malignant lymphoma of the cervix is a rare disease. Because the number of
      reports of this cancer is limited, there is no consensus on its management,
      prognosis or the efficacy of various treatments. Primary malignant lymphoma of
      the cervix stage Ib was diagnosed in a 25-year-old woman. The patient was treated
      with 6 courses of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine,
      and prednisone). Clinical and pathological responses were complete. This case
      supports current thinking in that, in selected young patients with primary
      malignant lymphoma of the cervix who desire to preserve fertility and ovarian
      functions, combination chemotherapy regimens such as CHOP are the treatment of
      choice.

PMID- 18712993
TI  - Evolution of phage display: from bioactive peptides to bioselective
      nanomaterials.
AB  - BACKGROUND: New phage-derived biorecognition nanomaterials have emerged recently
      as a result of the in-depth study of the genetics and structure of filamentous
      phage and the evolution of phage display technology. OBJECTIVE: This review
      focuses on the progress made in the development of these new nanomaterials and
      discusses the prospects of using phage as a bioselectable molecular recognition
      interface in medical and technical devices. METHODS: The author used data
      obtained both in his research group and sourced using Science Citation Index (Web
      of Science) search resources. RESULTS/CONCLUSION: The merging of phage display
      technologies with nanotechnology over the past few years has proved promising and
      has already shown its vitality and productivity by contributing vigorously to
      different areas of medicine and technology, such as medical diagnostics and
      monitoring, molecular imaging, targeted drug and gene delivery, vaccine
      development, as well as bone and tissue repair.

PMID- 18712994
TI  - Combinatorial design of biomaterials for drug delivery: opportunities and
      challenges.
AB  - BACKGROUND: The rational design of biodegradable polymeric devices for controlled
      drug delivery and tissue engineering is an important area of research for
      advancing new therapies for cancer, diabetes and immune-related disorders. In an
      era of escalating costs for discovery-based research, there is an urgent need to
      develop new and rapid methods to design drug delivery systems. OBJECTIVE/METHODS:
      By merging this field of study with rapid and high throughput methods of design,
      optimization and development, researchers have been able to accelerate the
      discovery and design processes for these devices. Combinatorial research enables
      the rapid identification of key regions of interest. CONCLUSION: This review
      focuses on the opportunities and challenges in the area of combinatorial
      biomaterials design for drug delivery, as there has been a great deal of
      significant progress over the past decade to propel this approach for the
      rational design of biomaterials.

PMID- 18712995
TI  - Advances in non-viral gene delivery: using multifunctional envelope-type nano
      device.
AB  - BACKGROUND: Low transfection efficiency is an obstacle to the clinical use of non
      viral gene vectors. Effective non-viral vectors require the ability to control
      intracellular trafficking of gene vectors for the delivery of exogenous DNA to
      the nucleus. OBJECTIVE: To overcome multiple intracellular barriers, various
      types of devices must be integrated into one nano-particle so that each device
      performs its function at the appropriate location at the desired time. Such a
      strategy requires an understanding, based on quantitative information, of the
      rate-limiting processes that hinder intracellular trafficking. METHODS: In this
      review, advancements in the development of multifunctional envelope-type nano
      devices (MEND) are discussed. In particular, a novel method to quantitatively
      evaluate the rate-limiting steps in intracellular trafficking, based on a
      comparison of viral and non-viral gene-delivery systems, is described.
      CONCLUSION: MENDs are useful to integrate various kinds of devices to overcome
      intracellular barriers into one particle. Comparison of intracellular trafficking
      between adenoviruses and non-viral vectors indicates that a postnuclear delivery
      process is an important rate-limiting step for efficient transfection with non
      viral vectors.

PMID- 18712997
TI  - Mitochondria targeting delivery of nucleic acids.
AB  - BACKGROUND: Mitochondria are intracellular organelles involved in energy
      production, which play important roles in metabolism. Consequently, mutation in
      mitochondrial DNA may have adverse effects on the host organism. This hypothesis
      is supported by increasing number of reports that associate various diseases with
      the mutation of the mitochondrial genome. Therefore, new therapy methods for
      targeting mitochondria genome should be developed for the treatment of these
      diseases. OBJECTIVES: The current progress in mitochondrial targeting gene
      delivery is discussed and future direction is suggested. METHODS: Recent research
      progress in this field is briefly introduced, and successes and obstacles in
      research are discussed. RESULTS/CONCLUSION: Delivery of antisense DNA using
      lipophilic cation showed possible therapeutic effect in vitro. Delivery of tRNA
      is also another possible approach to correct tRNA mutations. However, research
      into the delivery of protein expression system using liposome and polymer has
      been very limited. The results suggest that more research is required to address
      the problems in mitochondrial targeting gene delivery. Here, we suggest
      'multifunctional multilamella vesicular or multifunctional multi-vesicular (MMV)'
      for efficient mitochondrial targeting DNA delivery.

PMID- 18712996
TI  - The role of biomimetism in developing nanostructured inorganic matrices for drug
      delivery.
AB  - BACKGROUND: Biomimetism of synthetic biomaterials can be carried out at different
      levels, such as composition, structure, morphology, bulk and surface chemical
      physical properties. Biomaterials can be turned into biomimetic imprinting of all
      these characteristics in order not only to optimise their interaction with
      biological tissues, but also to mimic biogenic materials in their
      functionalities. OBJECTIVE: This review outlines the biomimetic chemical-physical
      properties of inorganic matrices in controlling drug release. METHODS: This
      review is restricted to phosphates and silica among inorganic biomaterials
      proposed as drug delivery vehicles. CONCLUSION: By mimicking nature, we can
      design and synthesise inorganic smart materials that are reactive towards
      biological tissues and can release bioactive molecules by a kinetic that is
      controlled not only by the matrix tailored chemical-physical properties, but also
      by the response to stimuli induced by physiological or pathological processes.

PMID- 18712998
TI  - Polyanhydrides as localized drug delivery carrier: an update.
AB  - BACKGROUND: There is a continuing thrust to increase the efficacy and reduce the
      toxicity of existing and new drug molecules for their better usage to treat
      disease. Localized drug delivery has been explored in the same way, which can
      provide a platform to target local diseased tissues and can reduce the burden on
      the body by reducing the dose size and hence the dose-related toxicity of the
      molecules. Various polymers have evolved for the purpose of localized drug
      delivery, however, polyanhydrides are considered the best, supported by products
      in the clinical phases. OBJECTIVE: To demonstrate the advantages of localized
      delivery using basic concepts and describing polyanhydride carrier with products
      such as Gliadel and Septacin. METHODS: The rationale behind localized drug
      delivery and the carrier for the same are dealt with. Polyanhydrides discussed in
      detail are those from subclasses that have been given less emphasis previously
      and have been developed or investigated in the last 5 years. RESULTS/CONCLUSION:
      From the recent update on polyanhydrides, it can be concluded that these polymers
      have great potential as localized drug delivery carriers due to the versatility
      of their properties. However, the quest to stabilize the system in order to
      achieve a long shelf life remains ongoing.

PMID- 18712999
TI  - What is the role of particle morphology in pharmaceutical powder aerosols?
AB  - BACKGROUND: The aerosol performance of a powder for inhalation drug delivery is
      controlled by a number of physicochemical properties of the formulation,
      including particle size, density and morphology. OBJECTIVE: The role of particle
      morphology in powder inhalers will be reviewed. METHODS: Original research
      publications in the literature about the contribution of particle morphology to
      the aerosol performance of pharmaceutical powders have been selected, including
      both the lactose carriers and the drugs. RESULTS/CONCLUSION: Existing data showed
      that morphology of both the lactose carrier and drug particle can affect the
      aerosol performance of powders significantly, a factor which should be taken into
      consideration during the development of dry powder inhalation products.

PMID- 18713000
TI  - Insulin delivery with FlexPen: dose accuracy, patient preference and adherence.
AB  - The introduction of insulin pens has helped improve adherence in Type 1 or 2
      diabetes, and reduce inaccurate dosing, fear of injection, and social
      embarrassment associated with vial and syringe. This report presents the
      published evidence base for the accuracy, patient preference and economic
      evaluation of one prefilled pen, FlexPen (Novo Nordisk A/S, Bagsvaerd, Denmark)
      and discusses recent changes to the design of this pen. Primary research
      publications that included the study of FlexPen were identified from various
      sources. Several studies have shown that FlexPen delivers high, medium and low
      doses of insulin significantly more accurately than vial and syringe, SoloStar
      (sanofi-aventis, Paris, France) or OptiClik (sanofi-aventis, Paris, France).
      Patients have also found FlexPen easier to use than vial and syringe. A Next
      Generation FlexPen has been developed, which maintains the demonstrated accuracy
      of FlexPen and is accompanied by a reduced injection force for simpler and more
      comfortable use, and clear colour scheme for insulin type to avoid medication
      errors.

PMID- 18713002
TI  - The role of glycosylation and domain interactions in the thermal stability of
      human angiotensin-converting enzyme.
AB  - The N and C domains of somatic angiotensin-converting enzyme (sACE) differ in
      terms of their substrate specificity, inhibitor profiling, chloride dependency
      and thermal stability. The C domain is thermally less stable than sACE or the N
      domain. Since both domains are heavily glycosylated, the effect of glycosylation
      on their thermal stability was investigated by assessing their catalytic and
      physicochemical properties. Testis ACE (tACE) expressed in mammalian cells,
      mammalian cells in the presence of a glucosidase inhibitor and insect cells
      yielded proteins with altered catalytic and physicochemical properties,
      indicating that the more complex glycans confer greater thermal stabilization.
      Furthermore, a decrease in tACE and N-domain N-glycans using site-directed
      mutagenesis decreased their thermal stability, suggesting that certain N-glycans
      have an important effect on the protein's thermodynamic properties. Evaluation of
      the thermal stability of sACE domain swopover and domain duplication mutants,
      together with sACE expressed in insect cells, showed that the C domain contained
      in sACE is less dependent on glycosylation for thermal stabilization than a
      single C domain, indicating that stabilizing interactions between the two domains
      contribute to the thermal stability of sACE and are decreased in a C-domain
      duplicating mutant.

PMID- 18713001
TI  - Some assembly required: dedicated chaperones in eukaryotic proteasome biogenesis.
AB  - The 26S proteasome is the key eukaryotic protease responsible for the degradation
      of intracellular proteins. Protein degradation by the 26S proteasome plays
      important roles in numerous cellular processes, including the cell cycle,
      differentiation, apoptosis, and the removal of damaged or misfolded proteins. How
      this 2.5-MDa complex, composed of at least 32 different polypeptides, is
      assembled in the first place is not well understood. However, it has become
      evident that this complicated task is facilitated by a framework of protein
      factors that chaperone the nascent proteasome through its various stages of
      assembly. We review here the known proteasome-specific assembly factors, most
      only recently discovered, and describe their potential roles in proteasome
      assembly, with an emphasis on the many remaining unanswered questions about this
      intricate process of assisted self-assembly.

PMID- 18713003
TI  - Fluoride complexes of oncogenic Ras mutants to study the Ras-RasGap interaction.
AB  - Down-regulation of Ras signalling is mediated by specific GTPase-activating
      proteins (GAPs), which stimulate the very slow GTPase reaction of Ras by 10(5)
      fold. The basic features of the GAP activity involve the stabilisation of both
      switch regions of Ras in the transition state, and the insertion of an arginine
      finger. In the case of oncogenic Ras mutations, the features of the active site
      are disturbed. To understand these features in more detail, we have investigated
      the effects of oncogenic mutations of Ras and compared the GAP-stimulated GTPase
      reaction with the ability to form GAP-mediated aluminium or beryllium fluoride
      complexes. In general we find a correlation between the size of the amino acid at
      position 12, the GTPase activity and ability to form aluminium fluoride
      complexes. While Gly12 is very sensitive to even the smallest possible structural
      change, Gly13 is much less sensitive to steric hindrance, but is sensitive to
      charge. Oncogenic mutants of Ras defective in the GTPase activity can however
      form ground-state GppNHp complexes with GAP, which can be mimicked by beryllium
      fluoride binding. We show that beryllium fluoride complexes are less sensitive to
      structural changes and report on a state close to but different from the ground
      state of the GAP-stimulated GTPase reaction.

PMID- 18713004
TI  - Docking of tryptophanyl [corrected tryptophan] analogs to trytophanyl-tRNA
      synthetase: implications for non-canonical amino acid incorporations.
AB  - Non-canonical amino acids (NAA), as building blocks for peptides and proteins
      during ribosomal translation, represent a nearly infinite supply of novel
      functions. The specific selection, activation and tRNA-charging of amino acids by
      aminoacyl-tRNA synthetases (AARS) in the aminoacylation reaction are essential
      steps. In most cases, aminoacylation of N(AA) is a good indication that the
      related amino acid will participate in ribosomal translation as well. However,
      testing the translational capacity of amino acid analogs has technical
      limitations. Therefore, a rapid and reliable in silico test for NAA recognition
      by AARS would be advantageous in experimental design. We chose tryptophanyl-tRNA
      synthetase from Escherichia coli as a model system for docking studies with
      various tryptophan analogs using the FlexX-Pharm strategy. We were able to
      calculate relative binding energies for Trp analogs in TrpRS that correlate well
      with their translational activities in E. coli. In particular, FlexX-Pharm
      predicted the binding sites of fluoro-, amino-, hydroxyl- and aza-containing Trp
      analogs within 1.5 A of Trp in the homology model of E. coli TrpRS. Therefore,
      the use of ligand docking prior to NAA incorporation experiments might provide a
      straightforward means for determining NAA that can be efficiently incorporated
      into a protein.

PMID- 18713005
TI  - Molecular mechanisms of aromatase inhibition by new A, D-ring modified steroids.
AB  - A recent approach for treatment and prevention of estrogen-dependent breast
      cancer focuses on the inhibition of aromatase, the enzyme that catalyzes the
      final step of estrogen biosynthesis. Some synthetic steroids, such as formestane
      and exemestane, resembling the natural enzyme substrate androstenedione, revealed
      to be potent and useful aromatase inhibitors (AIs) and were approved for the
      treatment of estrogen-dependent breast cancer in postmenopausal women. Recently,
      we found that five newly synthesized steroids with chemical features in the A-
      and D-rings considered important for drug-receptor interaction efficiently
      inhibit aromatase derived from human placental microsomes. In this work, these
      steroids showed a similar pattern of anti-aromatase activity in several aromatase
      expressing cell lines. 5alpha-androst-3-en-17-one and 3alpha,4alpha-epoxy-5alpha
      androstan-17-one were revealed to be the most potent inhibitors. These compounds
      induced a time-dependent inhibition of aromatase, showing to be irreversible AIs.
      The specific interactions of these compounds with aromatase active sites were
      further demonstrated by site-directed mutagenesis studies and evaluated by
      computer-aided molecular modeling. Both compounds were able to suppress hormone
      dependent proliferation of MCF-7aro cells in a dose-dependent manner. These
      findings are important for the elucidation of a structure-activity relationship
      on aromatase, which may help in the development of new AIs.

PMID- 18713006
TI  - A common binding motif for various bacteria of the bacteria-binding peptide
      SRCRP2 of DMBT1/gp-340/salivary agglutinin.
AB  - Abstract Salivary agglutinin (DMBT1SAG) is identical to lung glycoprotein-340 and
      encoded by deleted in malignant brain tumors-1. It is a member of the scavenger
      receptor cysteine-rich (SRCR) superfamily, proteins that have one or more SRCR
      domains. Salivary agglutinin plays a role in oral innate immunity by the binding
      and agglutination of oral streptococci. S. mutans has been shown to bind to a 16
      mer peptide (QGRVEVLYRGSWGTVC) located within the SRCR domains. Within this
      peptide, designated SRCR Peptide 2, residues VEVL and W were critical for
      binding. The aim of this study was to investigate binding of DMBT1SAG to other
      bacteria. Therefore, interaction between a series of bacteria and DMBT1(SAG),
      SRCR peptide 2 and its alanine substitution variants was studied in adhesion and
      agglutination assays. For different bacteria there was a highly significant
      correlation between adhesion to DMBT1SAG and adhesion to SRCR peptide 2
      suggesting that SRCR peptide 2 is the major bacteria binding site. An alanine
      substitution scan showed that 8 amino acids were involved in binding
      (xRVEVLYxxSWxxxx). The binding motifs varied for different species were found,
      but the residues VxVxY and W were always present. In conclusion, a common binding
      motif (RVEVLYxxxSW) within the SRCR domains is responsible for the broad bacteria
      binding spectrum of DMBT1SAG.

PMID- 18713007
TI  - Putative identification of an amphipathic alpha-helical sequence in hemolysin of
      Escherichia coli (HlyA) involved in transmembrane pore formation.
AB  - Abstract Escherichia coli hemolysin is a pore-forming protein belonging to the
      RTX toxin family. Cysteine scanning mutagenesis was performed to characterize the
      putative pore-forming domain of the molecule. A single cysteine residue was
      introduced at 48 positions within the sequence spanning residues 170-400 and
      labeled with the polarity-sensitive dye badan. Spectrofluorimetric analyses
      indicated that several amino acids in this domain are inserted into the lipid
      bilayer during pore formation. An amphipathic alpha-helix spanning residues 272
      298 was identified that may line the aqueous pore. The importance of this
      sequence was highlighted by the introduction of two prolines at positions 284 and
      287. Disruption of the helix structure did not affect binding properties, but
      totally abolished the hemolytic activity of the molecule.

PMID- 18713008
TI  - Cleaved SLPI, a novel biomarker of chymase activity.
AB  - Secretory leukocyte protease inhibitor (SLPI) is a protease inhibitor of the whey
      acidic protein-like family inhibiting chymase, chymotrypsin, elastase, proteinase
      3, cathepsin G and tryptase. Performing in vitro enzymatic assays using both
      Western blotting and liquid chromatography/mass spectrometry techniques we showed
      that, of the proteases known to interact with SLPI, only chymase could uniquely
      cleave this protein. The peptides of the cleaved SLPI (cSLPI) remain coupled due
      to the disulfide bonds in the molecule but under reducing conditions the cleavage
      can be observed as peptide products. Subsequent ex vivo studies confirmed the
      presence of SLPI in human saliva and its susceptibility to cleavage by chymase.
      Furthermore, inhibitors of chymase activity are able to inhibit this cleavage.
      Human saliva from both normal and allergic individuals was analyzed for levels of
      cSLPI and a correlation between the level of cSLPI and the extent of allergic
      symptoms was observed, suggesting the application of cSLPI as a biomarker of
      chymase activity in humans.

PMID- 18713009
TI  - Expression of tissue and plasma kallikreins and kinin B1 and B2 receptors in lung
      cancer.
AB  - Tissue kallikrein (hK1) and plasma kallikrein (PK, hKB1) are serine proteases
      that produce biologically active kinin peptides from endogenous kininogen
      substrates. There is evidence linking the kallikreins and the mitogenic kinin
      peptides to carcinogenesis. The aim of this study was to investigate the
      expression of tissue prokallikrein (pro-hK1), plasma prekallikrein (PPK, pre
      hKB1) and kinin B1 and B2 receptor proteins in different subtypes of lung cancer.
      Immunohistochemistry, using specific antibodies, was performed on archived normal
      lung sections and sections from adenocarcinomas, squamous cell carcinomas, large
      cell carcinomas, small cell carcinomas and carcinoid tumours of the lung.
      Immunoperoxidase labelling was visualised by brightfield microscopy and
      immunofluorescence labelling by confocal microscopy. Extensive cytoplasmic
      expression of pro-hK1 and PPK was observed, which was similar in small cell and
      non-small cell tumours. However, nuclear labelling for the kallikreins was absent
      or limited. The kinin B1 and B2 receptors were highly expressed in the cytoplasm
      of all tumour types and in the nuclei of non-small cell tumours. Further studies
      are required to assess the functional significance of the expression of hK1, PK
      and kinin receptors in lung tumours, and whether any of these proteins may be
      potential biomarkers for specific subtypes of lung carcinoma.

PMID- 18713010
TI  - Mechanism of methaemoglobin breakdown by the lysine-specific gingipain of the
      periodontal pathogen Porphyromonas gingivalis.
AB  - Abstract The R- and K-gingipain proteases of Porphyromonas gingivalis are
      involved in proteolysis of haemoglobin from which the defensive dimeric haem
      pigment is formed. Whilst oxyhaemoglobin is refractory towards K-gingipain,
      methaemoglobin is rapidly degraded. Ligation of methaemoglobin with N3-, which
      effectively blocks haem dissociation from the protein, prevented haemoglobin
      breakdown. Haem-free globin was rapidly degraded by K-gingipain. These data
      emphasise the need for haemoglobin oxidation which encourages haem dissociation
      and makes the haem-free globin susceptible to proteolytic attack.

PMID- 18713011
TI  - Fast in vitro translation system immobilized on a surface via specific
      biotinylation of the ribosome.
AB  - The ribosome is the macromolecular machine responsible for translating the
      genetic code into polypeptide chains. Despite impressive structural and kinetic
      studies of the translation process, a number of challenges remain with respect to
      understanding the dynamic properties of the translation apparatus. Single
      molecule techniques hold the potential of characterizing the structural and
      mechanical properties of macromolecules during their functional cycles in real
      time. These techniques often necessitate the specific coupling of biologically
      active molecules to a surface. Here, we describe a procedure for such coupling of
      functionally active ribosomes that permits single-molecule studies of protein
      synthesis. Oxidation with NaIO4 at the 3' end of 23S rRNA and subsequent reaction
      with a biotin hydrazide produces biotinylated 70S ribosomes, which can be
      immobilized on a streptavidin-coated surface. The surface-attached ribosomes are
      fully active in poly(U) translation in vitro, synthesizing poly(Phe) at a rate of
      3-6 peptide bonds/s per active ribosome at 37 degrees C. Specificity of binding
      of biotinylated ribosomes to a streptavidin-coated quartz surface was confirmed
      by observation of individual fluorescently labeled, biotinylated 70S ribosomes,
      using total internal reflection fluorescence microscopy. Functional interactions
      of the immobilized ribosomes with various components of the protein synthesis
      apparatus are shown by use of surface plasmon resonance.

PMID- 18713012
TI  - HIV-1 at the immunological and T-lymphocytic virological synapse.
AB  - Cell-cell transmission of human immunodeficiency virus type 1 (HIV-1) is
      considered the most effective mode of viral spread in T-lymphocyte cultures.
      Evidence has accumulated that HIV-1 assembles polarized synaptic-like structures,
      referred to as virological synapses, as specialized sites of viral transfer.
      Interestingly, it was recently also discovered that HIV-1 impairs the formation
      of the structurally similar immunological synapse, thereby modulating exogenous T
      lymphocyte stimulation to yield an optimal activation state for productive HIV-1
      infection. The careful dissection of these opposing effects will contribute to
      our understanding of retroviral spread and cellular signal transduction
      machineries.

PMID- 18713013
TI  - Pursuing different 'TRADDes': TRADD signaling induced by TNF-receptor 1 and the
      Epstein-Barr virus oncoprotein LMP1.
AB  - The pro-apoptotic tumor necrosis factor (TNF)-receptor 1-associated death domain
      protein (TRADD) was initially identified as the central signaling adapter
      molecule of TNF-receptor 1 (TNFR1). Upon stimulation with the pro-inflammatory
      cytokine TNFalpha, TRADD is recruited to the activated TNFR1 by direct
      interaction between the death domains of both molecules. TRADD mediates TNFR1
      activation of NF-kappaB and c-Jun N-terminal kinase (JNK), as well as caspase
      dependent apoptosis. Surprisingly, TRADD is also recruited by latent membrane
      protein 1 (LMP1), the major oncoprotein of the human Epstein-Barr tumor virus. By
      mimicking a constitutively active receptor, LMP1 is essential for B-cell
      transformation by the virus, activating NF-kappaB, phosphatidylinositol 3-kinase,
      JAK/STAT and mitogen-activated protein kinase signaling. In contrast to TNFR1,
      LMP1's interaction with TRADD is independent of a functional death domain. The
      unique structure of the LMP1-TRADD complex dictates an unusual type of TRADD
      dependent NF-kappaB signaling and subverts TRADD's potential to induce apoptosis.
      This article provides an overview of TNFR1 and LMP1 signal transduction with a
      focus on TRADD's functions in apoptotic and transforming signaling, incorporating
      recent results from TRADD RNAi and knockout studies.

PMID- 18713014
TI  - RNA viruses and the mitogenic Raf/MEK/ERK signal transduction cascade.
AB  - The Raf/MEK/ERK signal transduction cascade belongs to the mitogen-activated
      protein kinase (MAPK) cascades. Raf/MEK/ERK signaling leads to stimulus-specific
      changes in gene expression, alterations in cell metabolism or induction of
      programmed cell death (apoptosis), and thus controls cell differentiation and
      proliferation. It is induced by extracellular agents, including pathogens such as
      RNA viruses. Many DNA viruses are known to induce cellular signaling via this
      pathway. As these pathogens partly use the DNA synthesis machinery for their
      replication, they aim to drive cells into a proliferative state. In contrast, the
      consequences of RNA virus-induced Raf/MEK/ERK signaling were less clear for a
      long time, but since the turn of the century the number of publications on this
      topic has rapidly increased. Research on this virus/host-interaction will broaden
      our understanding of its relevance in viral replication. This important control
      center of cellular responses is differently employed to support the replication
      of several important human pathogenic RNA viruses including influenza, Ebola,
      hepatitis C and SARS corona viruses.

PMID- 18713015
TI  - Sabotage of antiviral signaling and effectors by influenza viruses.
AB  - Vertebrate cells activate multiple signaling modules upon virus infection to
      eliminate the invading pathogen and to prevent the establishment of a persistent
      infection. A major immediate response pathway is controlled by the RNA helicases
      RIG-I and MDA5, which, after recognition of viral nucleic acids, signal induction
      of the interferon (IFN)-alpha/beta cytokine family that upregulates numerous
      antiviral effector proteins. Virulent viruses, in contrast, have learned during
      co-evolution with their hosts to manipulate or avoid this response in order to
      prevail in a repulsive environment. Focusing on the influenza viruses and their
      IFN-antagonistic NS1 proteins, we summarize recent progress in this rapidly
      evolving field at the intersection of virology and immunobiology involving
      studies of how viral pathogens induce and sabotage cellular defenses.

PMID- 18713016
TI  - Hepatitis C virus (HCV) employs multiple strategies to subvert the host innate
      antiviral response.
AB  - Hepatitis C virus (HCV) is a serious global health problem which accounts for
      approximately 40% of chronic liver diseases worldwide. HCV frequently establishes
      a persistent infection, although it is recognized and targeted by innate immunity
      as well as cellular and humoral immune mechanisms. This suggests that HCV has
      developed powerful strategies to escape elimination by innate and adaptive
      immunity. HCV-induced liver injury is thought to be mainly immune-mediated rather
      than due to direct cytopathic effects of the virus. Hence, therapeutic strategies
      should target those mechanisms favoring viral persistence since unspecific
      enhancement of host antiviral immunity may theoretically also promote liver
      injury. The present review summarizes our current understanding of how the
      hepatitis C virus interferes with the innate antiviral host-response to establish
      persistent infection.

PMID- 18713017
TI  - Influenza viruses and the NF-kappaB signaling pathway - towards a novel concept
      of antiviral therapy.
AB  - Influenza A virus remains a major public health concern, both in its annual toll
      in death and debilitation and its potential to cause devastating pandemics. Like
      any other virus, influenza A viruses are strongly dependent on cellular factors
      for replication. One of the hallmark signaling factors activated by viral
      pathogens is the transcription factor NF-kappaB. Activation of NF-kappaB leads to
      the up-regulation of a variety of antiviral genes. Thus, the factor is commonly
      regarded as a major regulator of the innate immune defense to infection. However,
      several recent studies indicate that influenza viruses have acquired the
      capability to reprogram this antiviral activity and to exploit the factor for
      efficient replication. These data provide novel insights into the
      pathophysiological function of NF-kappaB in the special environment of a virus
      infected cell. Furthermore, the unexpected viral dependency on a cellular
      signaling factor may pave the path for novel antiviral approaches targeting
      essential cellular components rather than viral factors.

PMID- 18713018
TI  - Specific inhibition of transcriptional activity of the constitutive androstane
      receptor (CAR) by the splicing factor SF3a3.
AB  - The constitutive androstane receptor (CAR) is a member of the nuclear receptor
      superfamily and plays an important role in the degradation of xenobiotics in the
      liver. Using yeast two-hybrid screening, we identified SF3a3, a 60-kDa subunit of
      the splicing factor 3a complex, as a specific CAR-interacting protein. We further
      confirmed their interaction by both co-immunoprecipitation and GST pull-down
      assay. Functional studies showed that overexpression of SF3a3 inhibited the
      reporter activity driven by a promoter containing CAR binding sequences by up to
      50%, whereas reduced expression of SF3a3 activated the same reporter activity by
      approximately three-fold. The inhibitory function of SF3a3 is independent of the
      presence of TCPOBOP, a CAR ligand. These data suggest that SF3a3 functions as a
      co-repressor of CAR transcriptional activity, in addition to its canonical
      function.

PMID- 18713019
TI  - Generation of synthetic RNA-based thermosensors.
AB  - Structured RNAs with fundamental sensory and regulatory potential have been
      discovered in all kingdoms of life. Bacterial RNA thermometers are located in the
      5'-untranslated region of certain heat shock and virulence genes. They regulate
      translation by masking the Shine-Dalgarno sequence in a temperature-dependent
      manner. To engineer RNA-based thermosensors, we used a combination of computer
      based rational design and in vivo screening. After only two rounds of selection,
      several RNA thermometers that are at least as efficient as natural thermometers
      were obtained. Structure probing experiments revealed temperature-dependent
      conformational changes in these translational control elements. Our study
      demonstrates that temperature-controlled RNA elements can be designed by a simple
      combined computational and experimental approach.

PMID- 18713020
TI  - Impaired synthesis of heme oxygenase-1 in Fanconi anemia cells can be rescued by
      transfection of Fanconi wild-type cDNA.
AB  - Fanconi anemia is a fatal, hereditary chromosome instability syndrome of early
      childhood with progressive pancytopenia and cancer-proneness. Hypersensitivity to
      alkylating agents points to DNA repair inefficiency. Excess reactive oxygen
      intermediates and hypersensitivity to oxygen, all features of Fanconi anemia
      cells, give evidence for a disturbed oxidative metabolism. Here, we report that
      expression of the inducible heme oxygenase-1, an essential antioxidative defense
      protein, is impaired in Fanconi anemia cells and can be reinstated with the
      transfection of Fanconi A wild-type cDNA. A causative interaction of Fanconi
      anemia proteins with transcription of selected proteins is indicated. The results
      enlighten the oxygen sensitivity in Fanconi anemia.

PMID- 18713021
TI  - Effects of the Cdc2-like kinase-family and DNA topoisomerase I on the alternative
      splicing of eNOS in TNF-alpha-stimulated human endothelial cells.
AB  - Nitric oxide (NO) is synthesized by endothelial nitric oxide synthase (eNOS) and
      plays an important role in vascular homeostasis and cardiovascular diseases. It
      has recently been shown that increased expression of alternatively spliced eNOS
      isoforms eNOS 13A, B and C and heterodimerization with 'full-length' eNOS is
      associated with a decreased eNOS activity. The regulatory pathways enabling this
      phenomenon are completely unknown. This study examined the effect of Cdc2-like
      kinases and DNA topoisomerase I on eNOS splicing in TNF-alpha-induced human
      umbilical vein endothelial cells (HUVECs). We found that inhibition of DNA
      topoisomerase I, but not Cdc2-like kinases, prevents the TNF-alpha-induced
      increase in eNOS isoform expression and NO reduction in HUVEC. Moreover, we show
      that the inhibition of DNA topoisomerase I or the Cdc2-like kinases differently
      modulates the phosphorylation of the serine/arginine-rich proteins SRp75 and
      SRp55. Our results demonstrate, for the first time, that DNA topoisomerase I but
      not Cdc2-like kinases serves as an important regulator of the differential eNOS
      isoform expression in endothelial cells, thereby modulating the TNF-alpha-induced
      eNOS activity switch.

PMID- 18713022
TI  - Cytotoxic and peptidase inhibitory activities of selected non-hepatotoxic cyclic
      peptides from cyanobacteria.
AB  - Toxic cyanobacterial blooms are a rich source of metabolites having a variety of
      biological activities. Two main groups of cyclic peptides, depsipeptides and
      ureido linkage-containing peptides, reportedly inhibit serine peptidases. We
      characterised their inhibitory properties against selected peptidases and
      investigated their influence on cell viability. The depsipeptide planktopeptin
      BL1125 is a strong linear competitive tight-binding inhibitor of leukocyte
      (K(i)=2.9 nm) and pancreatic (K(i)=7.2 nm) elastase and also of chymotrypsin
      (K(i)=6.1 nm). Anabaenopeptins B and F show no inhibition against chymotrypsin,
      but inhibit both elastases. The tested cyclic peptides do not inhibit trypsin,
      urokinase, kallikrein 1 or cysteine peptidases. All three tested cyanopeptides
      show no short-term cytotoxicity in concentrations of up to 10 mum, but impair the
      metabolic activity of normal human astrocytes after prolonged exposure (48-96 h),
      whereas glioblastoma cells, tumour cells of the same type, are resistant. Strong
      inhibition and relative selectivity of the tested cyanopeptides suggests that
      they are potential candidates for application in inflammatory diseases and
      possibly some types of cancers.

PMID- 18713023
TI  - Misinterpreting the therapeutic effects of small interfering RNA caused by immune
      stimulation.
AB  - Activation of innate immunity has direct effects in modulating viral replication,
      tumor growth, angiogenesis, and inflammatory and other immunological processes.
      It is now established that unmodified siRNA can activate this innate immune
      response and therefore there is real potential for siRNA to elicit nonspecific
      therapeutic effects in a wide range of disease models. Here we demonstrate that
      in a murine model of influenza infection, the antiviral activity of siRNA is due
      primarily to immune stimulation elicited by the active siRNA duplexes and is not
      the result of therapeutic RNA interference (RNAi) as previously reported. We show
      that the misinterpretation stems from the use of a particular control green
      fluorescent protein (GFP) siRNA that we identify as having unusually low
      immunostimulatory activity compared with the active anti-influenza siRNA.
      Curiously, this GFP siRNA has served as a negative control for a surprising
      number of groups reporting therapeutic effects of siRNA. The inert immunologic
      profile of the GFP sequence was unique among a broad panel of published siRNAs,
      all of which could elicit significant interferon induction from primary immune
      cells. This panel included eight active siRNAs against viral, angiogenic, and
      oncologic targets, the reported therapeutic efficacy of which was based on
      comparison with the nonimmunostimulatory GFP siRNA. These results emphasize the
      need for researchers to anticipate, monitor, and adequately control for siRNA
      mediated immune stimulation and calls into question the interpretation of
      numerous published reports of therapeutic RNAi in vivo. The use of chemically
      modified siRNA with minimal immunostimulatory capacity will help to delineate
      more accurately the mechanism of action underlying such studies.

PMID- 18713024
TI  - Comparative characteristics of mesenchymal stem cells from human bone marrow and
      placenta: CD10, CD49d, and CD56 make a difference.

PMID- 18713025
TI  - Pediatric thyroid-associated orbitopathy: the Children's Hospital of Philadelphia
      experience and literature review.
AB  - BACKGROUND: As Graves' disease is uncommon in children, Graves' eye disease
      should be even more unusual. Here we report our experience with Graves' eye
      disease at the Children's Hospital of Philadelphia and review the literature on
      ophthalmic findings in children with Graves' disease. SUMMARY: A retrospective
      review identified 152 children with Graves' disease seen in the endocrinology
      clinic of the Children's Hospital of Philadelphia over a 3-year period. Of this
      cohort, only 26 (17%) were referred to ophthalmology because of prominent
      ophthalmic manifestations. The ages of the patients ranged from 4 months to 17
      years. Sixteen of 26 patients were female. Most patients had mild findings
      consistent with Graves' disease. Proptosis was noted in 10 of 26 (38%). Lid
      retraction was present in 6 of 26 (23%). Mild corneal punctuate staining was
      identified in only 3 of the 26 patients (12%). No patients had strabismus or
      optic neuropathy. Three newly diagnosed Graves' patients who were seen as the
      retrospective review was being completed were all girls. All three had normal
      vision, motility, and fundus exams. Two had mild proptosis, lid retraction, and
      lid lag on down gaze. None had corneal, motility, or optic nerve pathology. These
      findings are consistent with previous studies in the literature. CONCLUSIONS: Eye
      findings in pediatric Graves' disease are usually mild and typically respond to
      local measures and control of disturbed thyroid function. Surgery is indicated in
      a small number of patients for cornea exposure or appearance issues. Graves'
      disease-associated optic neuropathy has never been reported in the pediatric
      population.

PMID- 18713026
TI  - Cytokines, Graves' disease, and thyroid-associated ophthalmopathy.
AB  - Graves' disease, an autoimmune process associated with thyroid dysfunction, can
      also manifest as remodeling of orbital connective tissue. Affected tissues
      exhibit immune responses that appear to be orchestrated by resident cells and
      those recruited from the bone marrow through their expression and release of
      cytokines and surface display of cytokine receptors. Cytokines are small
      molecules produced by many types of cells, including those of the "professional"
      immune system. Aberrant cytokine expression appears to play an important role in
      the pathogenesis of many human diseases, including thyroid autoimmunity. The
      skewed pattern of cytokine expression in the thyroid, including the T helper cell
      bias, may condition the response to apoptotic signals and determine the
      characteristics of an autoimmune reaction. Furthermore, chemoattractant
      cytokines, including IL16, RANTES, and CXCL10, elaborated by resident cells in
      the thyroid and orbit may provoke mononuclear cell infiltration. Other cytokines
      may drive cell activation and tissue remodeling. Thus cytokines and the signaling
      pathways they activate represent attractive therapeutic targets. Interruption of
      these might alter the natural course of Graves' disease and its orbital
      manifestations.

PMID- 18713027
TI  - Biologic therapeutics in thyroid-associated ophthalmopathy: translating disease
      mechanism into therapy.
AB  - Graves' disease (GD) is a systemic autoimmune disease which targets the thyroid,
      orbit, and skin. Thyroid-associated ophthalmopathy (TAO) refers specifically to
      the orbital and periorbital manifestations of GD. Several important concepts have
      emerged from our enhanced understanding of the molecular mechanisms of the
      disease. Considerable debate remains concerning the specific identity and roles
      of inflammatory T-cell subsets, soluble and contact-mediated signalling, and
      autoantigens driving TAO. However B and T lymphocytes appear central in the
      process through production of disease mediators including activating
      autoantibodies to the thyrotropin receptor and insulin-like growth factor-1
      receptor; cytokines including IL-1beta, IL-6, and IL-16; and chemokines including
      RANTES. Many of these molecules appear central to the inflammation, accumulation
      of extracellular matrix macromolecules, and fibrosis in the disease. Novel
      therapeutics targeting other autoimmune diseases may provide an opportunity for
      disrupting disease pathogenesis. It is imperative that agents targeting B-and T
      cell functions be further evaluated in the treatment of aggressive forms of TAO
      utilizing multicenter clinical trials that allow adequate statistical power and
      sample size.

PMID- 18713028
TI  - High prevalence of thyroid autoimmunity in Apulian patients with autoimmune
      polyglandular syndrome type 1.

PMID- 18713029
TI  - Infinite models in scoliosis: a review of the literature and analysis of personal
      experience.
AB  - The purpose of this study was to introduce infinite models in scoliosis and to
      analyze personal experience. Based on a three-dimensional patient-specific finite
      element model of the spine, rib cage, pelvis and abdomen, a parametric individual
      model of a thoracolumbosacral orthosis was built. Three standard strap tensions
      (20, 40, 60 N) were loaded on the back of the brace to simulate the strap
      tension. The I-Scan distribution pressure measurement system was used to measure
      the pressure of the different regions and the equivalent forces in these regions
      were calculated. The spinal curve changes and the forces acted on the brace
      generated by the strap tension were evaluated and compared with the measurement
      results. The reduction of the coronal curvature was approximately 60% for a strap
      tension of 60 N. The sacral slope and the lordosis were partially reduced in this
      case. The brace modified the axial rotation at the deformed vertebrae. The forces
      generated in finite element analysis were in good agreement with the measurement.
      The findings supported the feasibility of such an approach to analyze individual
      bracing biomechanics, which may be useful in the design of more effective
      individual braces.

PMID- 18713030
TI  - Quorum sensing in staphylococci.
AB  - The staphylococcal agr locus encodes a quorum sensing (QS) system that controls
      the expression of virulence and other accessory genes by a classical two
      component signaling module. Like QS modalities in other Gram-positive bacteria,
      agr encodes an autoactivating peptide (AIP) that is the inducing ligand for AgrC,
      the agr signal receptor. Unlike other such systems, agr variants have arisen that
      show strong cross-inhibition in heterologous combinations, with important
      evolutionary implications. Also unlike other systems, the effector of global gene
      regulation in the agr system is a major regulatory RNA, RNAIII. In this review,
      we describe the functions of the agr system's elements, show how they interact to
      bring about the regulatory response, and discuss the role of QS in staphylococcal
      pathobiology. We conclude with the suggestion that agr autoactivation, unlike
      classical enzyme induction, can occur under suboptimal conditions and can
      distinguish self from non-self by inducing an exclusive and coordinated
      population wide response.

PMID- 18713031
TI  - The genetics and cell biology of Wolbachia-host interactions.
AB  - Wolbachia are gram-negative bacteria that are widespread in nature, carried by
      the majority of insect species as well as some mites, crustaceans, and filarial
      nematodes. Wolbachia can range from parasitic to symbiotic, depending upon the
      interaction with the host species. The success of Wolbachia is attributed to
      efficient maternal transmission and manipulations of host reproduction that favor
      infected females, such as sperm-egg cytoplasmic incompatibility (CI). Much
      remains unknown about the mechanistic basis for Wolbachia-host interactions. Here
      we summarize the current understanding of Wolbachia interaction with insect
      hosts, with a focus on Drosophila. The areas of discussion include Wolbachia
      transmission in oogenesis, Wolbachia distribution in spermatogenesis, induction
      and rescue of the CI phenotype, Wolbachia genomics, and Wolbachia-membrane
      interactions.

PMID- 18713033
TI  - Photo quiz. A 53-year-old man with a large air bubble in his chest.

PMID- 18713035
TI  - Moxifloxacin monotherapy in severe pneumonia: do we really need it?

PMID- 18713037
TI  - Inappropriate use of carbapenems in Thailand: a need for better education on de
      escalation therapy.

PMID- 18713038
TI  - Fatal bacteremic mycotic aneurysm complicated by acute renal failure caused by
      daptomycin-nonsusceptible, vancomycin-intermediate, and methicillin-resistant
      Staphylococcus aureus.

PMID- 18713040
TI  - Tenosynovitis caused by Mycobacterium arupense in a patient with diabetes
      mellitus.

PMID- 18713039
TI  - Maculopapular rash induced by oral vancomycin.

PMID- 18713044
TI  - Update on the appropriate use of meropenem for the treatment of serious bacterial
      infections.

PMID- 18713045
TI  - Impact of antibiotic resistance in gram-negative bacilli on empirical and
      definitive antibiotic therapy.
AB  - Serious infections with gram-negative pathogens continue to be associated with
      considerable mortality. Increasing antibiotic resistance in organisms such as
      Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae is
      contributing to difficulties with choosing antibiotics to prescribe for these
      infections. Optimization of therapy against these organisms starts with the
      initial empirical antibiotic choice. Surveillance data and hospital or unit
      antibiograms may inform this decision, although individualization of the initial
      regimen on the basis of prior antibiotic use and prior isolation of resistant
      pathogens may be more important. Combinations of antibiotics are often required
      empirically, and "combination antibiograms" may need to be developed for this
      purpose. Preliminary data suggest that extending the time over which a dose of
      antipseudomonal beta-lactam antibiotics is infused may improve clinical outcomes;
      however, this idea remains to be confirmed in randomized trials. The role of
      direct susceptibility testing in aiding more-rapid initiation of appropriate
      antibiotic therapy is also being studied. When identification and susceptibility
      testing is complete, the antibiotic regimen for infections due to gram-negative
      pathogens can be "fine tuned." On some occasions, this fine tuning necessitates
      the introduction of "salvage" antibiotics, such as colistin or tigecycline; on
      others, it necessitates de-escalation and early termination of therapy. The lack
      of new antibiotic options against gram-negative pathogens underscores the need
      for optimization of current therapies and prevention of the spread of these
      organisms.

PMID- 18713046
TI  - The importance and future of antimicrobial surveillance studies.
AB  - Surveillance studies provide important information that allows for the
      identification of trends in pathogen incidence and antimicrobial resistance,
      including identification of emerging pathogens at national and global levels.
      Routine surveillance is critical for creating and refining approaches to
      controlling antimicrobial resistance and for guiding clinician decisions
      regarding appropriate treatment. The traditional approach has been to monitor
      pathogen antimicrobial susceptibility; numerous large studies have been
      performed, and their designs have evolved over time. Longitudinal studies are
      particularly useful because important information can be obtained by comparing
      data over time. Another approach to surveillance, that of monitoring
      antimicrobial use, can help to identify trends in dosing, to prevent the
      development of resistance. Several studies have incorporated this approach into
      their methods, and both large and small studies have attempted to correlate
      antimicrobial use data with antimicrobial resistance data. Overall, care must be
      taken to coordinate programs for optimal utilization of resources, to avoid
      duplication of effort.

PMID- 18713047
TI  - Broad-spectrum antimicrobials and the treatment of serious bacterial infections:
      getting it right up front.
AB  - The treatment of serious bacterial infections is complicated by the fact that
      time to initiation of effective antimicrobial therapy is a strong predictor of
      mortality. Therefore, therapy must be initiated before the causative pathogen is
      identified. However, inappropriate or inadequate initial empirical therapy is
      associated with increased mortality, morbidity, and length of hospital stay.
      Initial empirical therapy with broad-spectrum antimicrobials attempts to address
      this dilemma by "getting it right up front." The goal is to provide treatment
      active against the most likely pathogens until culture/susceptibility test
      results are obtained. After the causative pathogen is identified, streamlining to
      more-precise therapy of the shortest acceptable duration is implemented. In this
      way, the risks of death, morbid complications, increased duration of hospital
      stay (as a result of ineffective initial treatment), and emergence of resistance
      (due to extended treatment with broad-spectrum agents) are lowered. Improved
      clinical and economic outcomes after such an approach have been demonstrated.

PMID- 18713048
TI  - Pharmacokinetic and pharmacodynamic properties of meropenem.
AB  - Pharmacokinetic and pharmacodynamic profiles of antibiotics are important in
      determining effective dosing regimens. Although minimum inhibitory concentration
      (MIC) data reflect microbial susceptibility to an antibiotic, they do not provide
      dosing information. The integration of pharmacokinetic and microbiological data,
      however, can be used to design rational dosing strategies. Meropenem is a broad
      spectrum beta-lactam antibiotic that penetrates most body fluids and tissues
      rapidly after intravenous administration. Meropenem undergoes primarily renal
      elimination; therefore, dosage adjustment is required for patients with renal
      impairment. Meropenem is indicated for the treatment of complicated skin and skin
      structure infections, complicated intra-abdominal infections, and bacterial
      meningitis. Meropenem has time-dependent bactericidal activity; thus, the
      percentage of time that free-drug concentrations are higher than the MIC (%T>MIC)
      best characterizes the drug's pharmacodynamic profile (bactericidal target of
      approximately 40%T>MIC). Pharmacodynamic modeling can identify regimens with the
      greatest probability of attaining this target, and probabilities can be compared
      with clinical and microbiological responses in patients.

PMID- 18713049
TI  - Update on the efficacy and tolerability of meropenem in the treatment of serious
      bacterial infections.
AB  - Meropenem is a carbapenem antibiotic approved by the US Food and Drug
      Administration for the treatment of complicated skin and skin-structure
      infections, complicated intra-abdominal infections, and pediatric bacterial
      meningitis (in patients >or=3 months of age). In clinical trials, it also has
      shown efficacy as initial empirical therapy for the treatment of nosocomial
      pneumonia. Unlike other beta-lactam antibiotics, including third-generation
      cephalosporins, carbapenems have shown activity against extended-spectrum beta
      lactamase-producing and AmpC chromosomal beta-lactamase-producing bacteria.
      Compared with imipenem, meropenem is more active against gram-negative pathogens
      and somewhat less active against gram-positive pathogens, and it does not require
      coadministration of a renal dehydropeptidase inhibitor. In most comparative
      trials, clinical and bacteriological response rates with imipenem and meropenem
      were similar. Compared with clindamycin/tobramycin, meropenem is associated with
      a reduced length of hospital stay and a shorter duration of therapy among
      patients with complicated intra-abdominal infections. Meropenem is well tolerated
      by children and adults and has an acceptable safety profile. Alternative
      meropenem dosing strategies for the optimization of outcomes are under
      investigation.

PMID- 18713052
TI  - Automated surveillance for central line-associated bloodstream infection in
      intensive care units.
AB  - OBJECTIVE: To develop and evaluate computer algorithms with high negative
      predictive values that augment traditional surveillance for central line
      associated bloodstream infection (CLABSI). SETTING: Barnes-Jewish Hospital, a
      1,250-bed tertiary care academic hospital in Saint Louis, Missouri. METHODS: We
      evaluated all adult patients in intensive care units who had blood samples
      collected during the period from July 1, 2005, to June 30, 2006, that were
      positive for a recognized pathogen on culture. Each isolate recovered from
      culture was evaluated using the definitions for nosocomial CLABSI provided by the
      National Healthcare Safety Network of the Centers for Disease Control and
      Prevention. Using manual surveillance by infection prevention specialists as the
      gold standard, we assessed the ability of various combinations of dichotomous
      rules to determine whether an isolate was associated with a CLABSI. Sensitivity,
      specificity, and predictive values were calculated. RESULTS: Infection prevention
      specialists identified 67 cases of CLABSI associated with 771 isolates recovered
      from blood samples. The algorithms excluded approximately 40%-62% of the isolates
      from consideration as possible causes of CLABSI. The simplest algorithm, with 2
      dichotomous rules (ie, the collection of blood samples more than 48 hours after
      admission and the presence of a central venous catheter within 48 hours before
      collection of blood samples), had the highest negative predictive value (99.4%)
      and the lowest specificity (44.2%) for CLABSI. Augmentation of this algorithm
      with rules for common skin contaminants confirmed by another positive blood
      culture result yielded in a negative predictive value of 99.2% and a specificity
      of 68.0%. CONCLUSIONS: An automated approach to surveillance for CLABSI that is
      characterized by a high negative predictive value can accurately identify and
      exclude positive culture results not representing CLABSI from further manual
      surveillance.

PMID- 18713054
TI  - Drug interactions involving combination antiretroviral therapy and other anti
      infective agents: repercussions for resource-limited countries.

PMID- 18713053
TI  - Discordant QuantiFERON-TB Gold test results among US healthcare workers with
      increased risk of latent tuberculosis infection: a problem or solution?
AB  - OBJECTIVE: In late 2006, our hospital implemented use of the QuantiFERON-TB Gold
      (QFT-G) assay, a whole-blood interferon-gamma release assay, for detection of
      tuberculosis infection. All newly hired healthcare workers (HCWs) with positive
      Mantoux tuberculin skin test (TST) results were routinely tested with the QFT-G
      assay, to take advantage of its higher specificity. We then undertook a quality
      assurance review to evaluate the QFT-G test results in HCWs with multiple risk
      factors for latent tuberculosis infection (LTBI). METHODS: The clinical records
      for TST-positive HCWs tested with the QFT-G assay were reviewed. HCWs with 2 or
      more risk factors commonly associated with LTBI were classified as "increased
      risk" (IR). IR HCWs who had negative QFT-G test results underwent repeat QFT-G
      testing and were offered testing with a different interferon-gamma release assay
      (T-SPOT.TB) and with extended T cell stimulation assays. RESULTS: Of 143 TST
      positive HCWs tested with the QFT-G assay, 26 (18%) had positive results, 115
      (81%) had negative results, and 2 (1%) had indeterminate results. Of 82 IR HCWs,
      23 (28%) had positive QFT-G test results, and 57 (70%) had negative results. Of
      the 57 IR HCWs with negative results, 43 underwent repeat QFT-G testing: 41 had
      negative results again, and 2 had positive results. These 43 HCWs were also
      offered additional testing with the T-SPOT.TB diagnostic, and 36 consented: 31/36
      tested negative, and 5/36 tested positive. Extended assays using the antigens
      ESAT-6 and CFP-10 confirmed the positive results detected by the overnight assays
      and yielded positive results for an additional 7/36 (19%) of individuals;
      strikingly, all 36 HCWs had strongly positive test results with assays using
      purified protein derivative. CONCLUSIONS: The extreme discordance between the
      results of our clinical diagnostic algorithm and the results of QFT-G testing
      raises concern about the sensitivity of the QFT-G assay for detection of LTBI in
      our HCWs. Results of extended stimulation assays suggest that many of our IR HCWs
      have indeed been sensitized to Mycobacterium tuberculosis. It is possible that
      the QFT-G assay identifies those at higher reactivation risk rather than all
      previously infected, but, in the absence of long-term follow-up data, we should
      interpret negative QFT-G results with some caution.

PMID- 18713055
TI  - Solenopsin A, a venom alkaloid from the fire ant Solenopsis invicta, inhibits
      quorum-sensing signaling in Pseudomonas aeruginosa.
AB  - In Pseudomonas aeruginosa, quorum-sensing (QS) signaling regulates the expression
      of virulence factors and thus represents an attractive new target for anti
      infective therapy. In the present study, we investigated whether solenopsin A, a
      venom alkaloid from the fire ant, possessed agonistic or antagonistic QS
      signaling activity in P. aeruginosa. We evaluated the modulation of virulence
      factor expression and transcriptional levels of QS-regulated genes in P.
      aeruginosa by solenopsin A and demonstrated that solenopsin A efficiently
      disrupted QS signaling. Interestingly, exogenously added C(4)-homoserine lactone
      (HSL), but not 3-oxo-C(12)-HSL, restored P. aeruginosa QS signaling, suggesting
      that solenopsin A targets the C(4)-HSL-dependent rhl QS system.

PMID- 18713056
TI  - Supportive role played by precore and preS2 genomic changes in the establishment
      of lamivudine-resistant hepatitis B virus.
AB  - BACKGROUND: Hepatitis B virus (HBV) establishes lamivudine resistance via the
      resistance-causative rtM204V/I mutation and the replication-compensatory rtL180M
      mutation. However, both lamivudine-resistant viruses with and those without
      rtL180M can exist in clinical settings. To elucidate the differences between
      viruses with and those without rtL180M, we conducted full-length sequencing
      analysis of HBV derived from patients with type B chronic hepatitis showing
      lamivudine resistance. METHODS: The full-length HBV DNA sequences derived from 44
      patients showing lamivudine resistance were determined by polymerase chain
      reaction direct sequencing. Viral replicative competence was examined by in vitro
      transfection analysis using various HBV-expressing plasmids. RESULTS: Throughout
      the HBV genome, a precore-defective A1896 mutation and a short deletion in the
      preS2 gene were detected more frequently in viruses without rtL180M than in those
      with it (64% vs. 17% [P < .005] and 50% vs. 10% [P < .01], respectively). In
      vitro transfection analysis revealed that the level of reduction in intracellular
      viral replication caused by the introduction of lamivudine resistance-associated
      mutations was lower in precore-defective and preS2-deleted viruses than in wild
      type virus. CONCLUSIONS: Both the precore-defective mutation and the preS2
      deletion may play a supportive role in the replication of lamivudine-resistant
      HBV, which may be a reason for there being no need for the compensatory rtL180M
      mutation in lamivudine-resistant HBV possessing the precore and preS2 genomic
      changes.

PMID- 18713057
TI  - Functional gene polymorphisms in canadian aboriginal populations with high rates
      of tuberculosis.
AB  - The present study determined whether a pattern of functional single-nucleotide
      polymorphisms (SNPs) was present that could predispose a Dene cohort to a
      suboptimal response to Mycobacterium tuberculosis. Compared with a Caucasian
      cohort, the Dene and Cree were found to maintain a significantly higher frequency
      of SNPs associated with low expression of vitamin D receptor (VDR), interferon
      (IFN)-gamma (+874), and tumor necrosis factor-alpha (-308) and high production of
      monocyte chemoattractant protein (MCP)-1 (-2518) and interleukin (IL)-6 (-174).
      Given the roles played by IFN-gamma and VDR in facilitating macrophage
      containment of M. tuberculosis and the opposing role of MCP-1 and IL-6, the
      observed allelic variation by ethnicity may in part contribute to the high rates
      of tuberculosis among the Dene.

PMID- 18713058
TI  - Foodborne disease trends and reports.

PMID- 18713059
TI  - The complete genome sequence and analysis of the human pathogen Campylobacter
      lari.
AB  - Campylobacter lari is a member of the epsilon subdivision of the Proteobacteria
      and is part of the thermotolerant Campylobacter group, a clade that includes the
      human pathogen C. jejuni. Here we present the complete genome sequence of the
      human clinical isolate, C. lari RM2100. The genome of strain RM2100 is
      approximately 1.53 Mb and includes the 46 kb megaplasmid pCL2100. Also present
      within the strain RM2100 genome is a 36 kb putative prophage, termed CLIE1, which
      is similar to CJIE4, a putative prophage present within the C. jejuni RM1221
      genome. Nearly all (90%) of the gene content in strain RM2100 is similar to genes
      present in the genomes of other characterized thermotolerant campylobacters.
      However, several genes involved in amino acid biosynthesis and energy metabolism,
      identified previously in other Campylobacter genomes, are absent from the C. lari
      RM2100 genome. Therefore, C. lari RM2100 is predicted to be multiply auxotrophic,
      unable to synthesize eight different amino acids, acetyl-coA, and pantothenate.
      Additionally, strain RM2100 does not contain a complete TCA cycle and is missing
      the CydAB terminal oxidase of the respiratory chain. Defects in the amino acid
      biosynthetic pathways in this organism could be potentially compensated by the
      large number of encoded peptidases. Nevertheless, the apparent absence of certain
      key enzymatic functions in strain RM2100 would be expected to have an impact on
      C. lari biology. It is also possible that the reduction in the C. lari metabolic
      machinery is related to its environmental range and host preference.

PMID- 18713060
TI  - Analysis of AI-2/LuxS-dependent transcription in Campylobacter jejuni strain 81
      176.
AB  - Autoinducer-2 (AI-2) is a quorum-sensing signal molecule that controls a variety
      of cellular activities in response to cell density in both gram-negative and gram
      positive bacteria. The production of AI-2 is dependent upon LuxS, the last enzyme
      in the AI-2 biosynthesis pathway. For this study, we constructed a luxS null
      mutation (Delta luxS) in Campylobacter jejuni strain 81-176, and showed that it
      abolished AI-2 production. The Delta luxS mutant had a longer doubling time in
      Mueller-Hinton (MH) broth and reduced swarming on MH soft agar at 37 degrees C
      compared to the wild type (wt), whereas growth rate or swarming at 42 degrees C
      was not affected. The Delta luxS mutant was also more sensitive to hydrogen
      peroxide (H(2)O(2)) and cumene hydroperoxide than the wt by disc inhibition
      assays at 42 degrees C, though minimum inhibitory concentration comparisons were
      inconclusive. Differences in genome-wide gene expression between wt and Delta
      luxS mutant with and without H(2)O(2) treatments were compared using DNA
      microarrays. The genes that showed differential expressions (wt/Delta luxS)
      include operons/pathways involved in AI-2 synthesis and S-adenosylmethionine
      (SAM) metabolism (metE, metF, and pfs), flagellar assembly/regulation, stress
      response (ahpC, tpx, and groES), ABC transporters/efflux systems, and two genes
      of unknown function located downstream of luxS (Cj1199 and Cj1200). The wt/Delta
      luxS expression ratios of ahpC (encoding alkyl hydroperoxide reductase) and tpx
      (encoding thiol peroxidase) were increased only with H(2)O(2) treatment,
      consistent with our finding that the Delta luxS mutant exhibits higher
      sensitivity to oxidative stress than wt. Our microarray results agreed with the
      Delta luxS mutant phenotypes, and suggested that LuxS plays a role in central
      metabolism involving SAM metabolism, but it is uncertain whether AI-2 functions
      as a true quorum-sensing signal in C. jejuni.

PMID- 18713062
TI  - Examination of stress and virulence gene expression in Escherichia coli O157:H7
      using targeted microarray analysis.
AB  - Escherichia coli O157:H7 poses a threat to humans through food- and water-borne
      transmission. To investigate how environmental stresses affect the Escherichia
      coli O157:H7 transcriptome, we designed a targeted microarray consisting of
      stress response and virulence genes (n = 125) to analyze the impact of acidified
      (pH 3.5), cold (7.5 degrees C), and fresh tryptic soy broth (TSB) (37 degrees C)
      on E. coli O157:H7 stress response and virulence gene expression. Nutrient
      replenishment with fresh TSB resulted in 72 differentially expressed genes (> or
      = 1.5-fold change; p < 0.05), with 65 induced. All queried global and specific
      stress regulators were affected, as were 12 virulence genes. Cold-shocked cells
      displayed 17 differentially expressed genes, with 10 being induced. Induction of
      rpoS, members of the sigma(H) regulon (clpB, dnaK, ftsH), and acid resistance
      (AR) genes (gadA, gadX) was observed. Porin transcript (ompC, ompF) and gapA and
      tufA ancillary genes were repressed. Acid shock resulted in 24 differentially
      expressed genes, with 21 induced. No induction of any stationary phase AR system
      was observed, though acid-coping mechanisms were recruited, including mar and
      phoB induction, and repression of ompC and ompF. Stress regulators were induced,
      including relA, soxS, rpoE, and rpoH. The microarray data were validated by
      quantitative real-time polymerase chain reaction. Exposure to sublethal stress
      events led to the induction of diverse stress response networks. In the food
      chain, sublethal events may render cells increasingly resistant to future
      stresses, potentially leading to increased survival.

PMID- 18713061
TI  - Differential regulation of Listeria monocytogenes internalin and internalin-like
      genes by sigmaB and PrfA as revealed by subgenomic microarray analyses.
AB  - The Listeria monocytogenes genome contains more than 20 genes that encode cell
      surface-associated internalins. To determine the contributions of the alternative
      sigma factor sigma(B) and the virulence gene regulator PrfA to internalin gene
      expression, a subgenomic microarray was designed to contain two probes for each
      of 24 internalin-like genes identified in the L. monocytogenes 10403S genome.
      Competitive microarray hybridization was performed on RNA extracted from (i) the
      10403S parent strain and an isogenic Delta sigB strain; (ii) 10403S and an
      isogenic Delta prfA strain; (iii) a (G155S) 10403S derivative that expresses the
      constitutively active PrfA (PrfA*) and the Delta prfA strain; and (iv) 10403S and
      an isogenic Delta sigB Delta prfA strain. Sigma(B)- and PrfA-dependent
      transcription of selected genes was further confirmed by quantitative reverse
      transcriptase polymerase chain reaction. For the 24 internalin-like genes
      examined, (i) both sigma(B) and PrfA contributed to transcription of inlA and
      inlB, (ii) only sigma(B) contributed to transcription of inlC2, inlD, lmo0331,
      and lmo0610; (iii) only PrfA contributed to transcription of inlC and lmo2445;
      and (iv) neither sigma(B) nor PrfA contributed to transcription of the remaining
      16 internalin-like genes under the conditions tested.

PMID- 18713063
TI  - Bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP) for microbiome
      studies: bacterial diversity in the ileum of newly weaned Salmonella-infected
      pigs.
AB  - The microbiota of an animal's intestinal tract plays a vital role in the animal's
      overall health. There is a surprising scarcity of information on the microbial
      diversity in the gut of livestock species such as cattle and swine. Here we
      describe a bacterial 16S-based tag-encoded FLX amplicon pyrosequencing (bTEFAP)
      method that we have developed as a high-throughput universal tool for bacterial
      diversity, epidemiology, and pathogen detection studies. This method will allow
      hundreds of samples to be run simultaneously but analyzed individually or as
      groups. To test this new methodology, we individually evaluated the bacterial
      diversity in the ileum of 21 pigs. Ubiquitous bacteria detected in the newly
      weaned pigs were Clostridium spp., Lactobacillus spp., and Helicobacter spp. Many
      of the pigs had surprisingly low concentrations of beneficial bacteria such as
      Bifidobacterium spp. Only four of the pigs were shown to be positive for
      Salmonella spp. using traditional culture methods. A total of eight pigs were
      bTEFAP positive for Salmonella spp., including all four of the pigs that had been
      culture positive. Two of the pigs sampled were also positive for Campylobacter
      spp. tentative identified as jejuni. Using rarefaction curves modeled with the
      Richards equation, we estimated the maximum number of unique species level (3%
      dissimilarity) operational taxonomic units in the ileum of these pigs. These
      predictions indicated that there may be as many as 821 different species
      associated with the ileum in pigs. Together these data indicate a powerful
      potential of this technology in food safety and epidemiological and bacterial
      diversity applications. Using bTEFAP, we can expect to gain a better
      understanding of how the microbiome of an animal contributes to its health and
      well-being.

PMID- 18713064
TI  - Methods and tools for comparative genomics of foodborne pathogens.
AB  - A comparison of genome sequences and of encoded proteins with the database of
      existing annotated sequences is a useful approach to understand the information
      at the genome level. Here we demonstrate the utility of several DNA and protein
      sequence comparison tools to interpret the information obtained from several
      genome projects. Comparisons are presented between closely related strains of
      Escherichia coli commensal isolates, different isolates of O157:H7, and Shigella
      spp. It is expected that comparative genome analysis will generate a wealth of
      data to compare pathogenic isolates with varying levels of pathogenicity, which
      in turn may reveal mechanisms by which the pathogen may adapt to a particular
      nutrient supply in certain foods. These genome sequence analysis tools will
      strengthen foodborne pathogen surveillance and subsequent risk assessment to
      enhance the safety of the food supply.

PMID- 18713065
TI  - Impact of compounding error on strategies for subtyping pathogenic bacteria.
AB  - Comparative-omics will identify a multitude of markers that can be used for
      intraspecific discrimination between strains of bacteria. It seems intuitive that
      with this plethora of markers we can construct higher resolution subtyping assays
      using discrete markers to define strain "barcodes." Unfortunately, with each new
      marker added to an assay, overall assay robustness declines because errors are
      compounded exponentially. For example, the difference in accuracy of strain
      classification for an assay with 60 markers will change from 99.9% to 54.7% when
      average probe accuracy declines from 99.999% to 99.0%. To illustrate this effect
      empirically, we constructed a 19 probe bead-array for subtyping Listeria
      monocytogenes and showed that despite seemingly reliable individual probe
      accuracy (>97%), our best classification results at the strain level were <75%. A
      more robust strategy would use as few markers as possible to achieve strain
      discrimination. Consequently, we developed two variable number of tandem repeat
      (VNTR) assays (Vibrio parahaemolyticus and L. monocytogenes) and demonstrate that
      these assays along with a published assay (Salmonella enterica) produce robust
      results when products were machine scored. The discriminatory ability with four
      to seven VNTR loci was comparable to pulsed-field gel electrophoresis. Passage
      experiments showed some instability with ca. 5% of passaged lines showing
      evidence for new alleles within 30 days (V. parahaemolyticus and S. enterica).
      Changes were limited to a single locus and allele so conservative rules can be
      used to determine strain matching. Most importantly, VNTRs appear robust and
      portable and can clearly discriminate between strains with relatively few loci
      thereby limiting effects of compounding error.

PMID- 18713066
TI  - Effects of low-level ciprofloxacin challenge in the in vitro development of
      ciprofloxacin resistance in Campylobacter jejuni.
AB  - The effects on MIC values and the selection of different base substitutions in
      the quinolone resistance determining region (QRDR) of gyrA were studied on
      initially ciprofloxacin-susceptible Campylobacter jejuni strains by challenging
      them to 0.125 mg/L of ciprofloxacin. This ciprofloxacin challenge selected
      variants with ciprofloxacin MIC levels up to 32 mg/L. Repeated experiments under
      identical conditions resulted in different responses in MIC levels and
      alterations in the QRDR of gyrA. A characteristic outcome to ciprofloxacin
      challenges was the appearance of double peaks in the sequencing chromatograms of
      QRDR. This finding suggested the coexistence of subpopulations possessing Thr86 -
      > Ile and/or Asp90 --> Asn mutations alongside the unmutated parent population.
      In some cases, bacterial variants expressing ciprofloxacin-resistant phenotypes
      possessed no mutations in their QRDR. These variants were prone to regain
      susceptibility to ciprofloxacin rapidly after the removal of the selection
      pressure, whereas the QRDR-mutated variants persisted over several
      subcultivations in a medium without ciprofloxacin. In conclusion, a low
      ciprofloxacin concentration of 0.125 mg/L selects a variety of QRDR mutations and
      also a QRDR-independent resistance mechanism, which may coexist with each other
      in a C. jejuni population. Persistent ciprofloxacin challenge selects Thr86 -->
      Ile and/or Asp90 --> Asn mutants.

PMID- 18713068
TI  - Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible
      factor (HIF)-1alpha.
AB  - The transcription factor HIF (hypoxia-inducible factor) mediates a highly
      pleiotrophic response to hypoxia. Many recent studies have focused on defining
      the extent of this transcriptional response. In the present study we have
      analysed regulation by hypoxia among transcripts encoding human Fe(II)- and 2
      oxoglutarate-dependent oxygenases. Our results show that many of these genes are
      regulated by hypoxia and define two groups of histone demethylases as new classes
      of hypoxia-regulated genes. Patterns of induction were consistent across a range
      of cell lines with JMJD1A (where JMJD is Jumonji-domain containing) and JMJD2B
      demonstrating robust, and JMJD2C more modest, up-regulation by hypoxia.
      Functional genetic and chromatin immunoprecipitation studies demonstrated the
      importance of HIF-1alpha in mediating these responses. Given the importance of
      histone methylation status in defining patterns of gene expression under
      different physiological and pathophysiological conditions, these findings predict
      a role for the HIF system in epigenetic regulation.

PMID- 18713067
TI  - The PRH/Hex repressor protein causes nuclear retention of Groucho/TLE co
      repressors.
AB  - The PRH (proline-rich homeodomain) [also known as Hex (haematopoietically
      expressed homeobox)] protein is a transcription factor that functions as an
      important regulator of vertebrate development and many other processes in the
      adult including haematopoiesis. The Groucho/TLE (transducin-like enhancer) family
      of co-repressor proteins also regulate development and modulate the activity of
      many DNA-binding transcription factors during a range of diverse cellular
      processes including haematopoiesis. We have shown previously that PRH is a
      repressor of transcription in haematopoietic cells and that an Eh-1 (Engrailed
      homology) motif present within the N-terminal transcription repression domain of
      PRH mediates binding to Groucho/TLE proteins and enables co-repression. In the
      present study we demonstrate that PRH regulates the nuclear retention of TLE
      proteins during cellular fractionation. We show that transcriptional repression
      and the nuclear retention of TLE proteins requires PRH to bind to both TLE and
      DNA. In addition, we characterize a trans-dominant-negative PRH protein that
      inhibits wild-type PRH activity by sequestering TLE proteins to specific
      subnuclear domains. These results demonstrate that transcriptional repression by
      PRH is dependent on TLE availability and suggest that subnuclear localization of
      TLE plays an important role in transcriptional repression by PRH.

PMID- 18713069
TI  - The cytotoxic effect of unconjugated bilirubin in human neuroblastoma SH-SY5Y
      cells is modulated by the expression level of MRP1 but not MDR1.
AB  - In vitro and in vivo studies have demonstrated that UCB (unconjugated bilirubin)
      is neurotoxic. Although previous studies suggested that both MRP1 (multidrug
      resistance-associated protein 1) and MDR1 (multidrug resistance protein 1) may
      protect cells against accumulation of UCB, direct comparison of their role in UCB
      transport was never performed. To this end, we used an inducible siRNA (small
      interfering RNA) expression system to silence the expression of MRP1 and MDR1 in
      human neuroblastoma SH-SY5Y cells. The effects of in vitro exposure to clinically
      relevant levels of unbound UCB were compared between unsilenced (control) cells
      and cells with similar reductions in the expression of MRP1 or MDR1, documented
      by RT-PCR (reverse transcription-PCR) (mRNA), immunoblotting (protein), and for
      MDR1, the enhanced net uptake of a specific fluorescent substrate. Cytotoxicity
      was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium
      bromide] test. MRP1-deficient cells accumulated significantly more UCB and
      suffered greater cytotoxicity than controls. By contrast, MDR1-deficient cells
      exhibited UCB uptake and cytotoxicity comparable with controls. At intermediate
      levels of silencing, the increased susceptibility to UCB toxicity closely
      correlated with the decrease in the expression of MRP1, but not of MDR1. These
      data support the concept that limitation of cellular UCB accumulation, due to UCB
      export mediated by MRP1, but not MDR1, plays an important role in preventing
      bilirubin encephalopathy in the newborn.

PMID- 18713071
TI  - Human hair pigmentation--biological aspects.
AB  - Skin and hair colour contribute significantly to our overall visual appearance
      and to social/sexual communication. Despite their shared origins in the
      embryologic neural crest, the hair follicle and epidermal pigmentary units occupy
      distinct, although open, cutaneous compartments. They can be distinguished
      principally on the basis of the former's stringent coupling to the hair growth
      cycle compared with the latter's continuous melanogenesis. The biosynthesis of
      melanin and its subsequent transfer from melanocyte to hair bulb keratinocytes
      depend on the availability of melanin precursors and on a raft of signal
      transduction pathways that are both highly complex and commonly redundant. These
      signalling pathways can be both dependent and independent of receptors, act
      through auto-, para- or intracrine mechanisms and can be modified by hormonal
      signals. Despite many shared features, follicular melanocytes appear to be more
      sensitive than epidermal melanocytes to ageing influences. This can be seen most
      dramatically in hair greying/canities and this is likely to reflect significant
      differences in the epidermal and follicular microenvironments. The hair follicle
      pigmentary unit may also serve as an important environmental sensor, whereby hair
      pigment contributes to the rapid excretion of heavy metals, chemicals and toxins
      from the body by their selective binding to melanin; rendering the hair fibre a
      useful barometer of exposures. The recent availability of advanced cell culture
      methodologies for isolated hair follicle melanocytes and for intact anagen hair
      follicle organ culture should provide the research tools necessary to elucidate
      the regulatory mechanisms of hair follicle pigmentation. In the longer term, it
      may be feasible to develop hair colour modifiers of a biological nature to
      accompany those based on chemicals.

PMID- 18713072
TI  - In vitro evaluation of sun protection factors of sunscreen agents using a novel
      UV spectrophotometric technique.
AB  - A method for the in vitro determination of low- and high-value sun protection
      factors (SPF) of sunscreens using artificial substrates and a novel pseudo double
      beam (PDB) mode of operation of a standard double beam UV spectrophotometer is
      described. The method allows transmittance to be calculated from detector
      responses of reference and sample beams measured at different gain levels and
      facilitates the accurate quantification of low levels of electromagnetic
      radiation transmitted through highly absorbing samples. The spectrophotometer was
      modified to hold quartz diffusing plates on which a substrate [Transpore adhesive
      tape or human stratum corneum obtained from a skin surface biopsy (SSB)] and the
      sunscreens to be tested were applied. The PDB mode of operation increased the
      effective linear range of the detector response of the spectrophotometer by a
      factor of approximately 20000-fold, enabling the in vitro SPF determination
      technique to be applied to both high and low SPF value sunscreens. Eight
      commercial sunscreens with known SPF values ranging from 4 to 77, previously
      determined by in vivo methods, were tested in vitro using both test substrates
      and correlations between the in vivo and in vitro values were determined. SPF
      values determined using the in vitro method correlated well with the known in
      vivo results (Transpore tape, R(2) = 0.611; SSB, R(2) = 0.7928). The in vitro SPF
      obtained for one of the tested products differed substantially from the cited in
      vivo SPF value. Independent in vitro and in vivo re-evaluation of the SPF of this
      product matched the value predicted by the present method much more closely than
      the originally cited in vivo value. All determined SPFs were ordered correctly in
      comparison to in vivo ranking and the technique appeared to correctly identify a
      sunscreen that had a labelled SPF value that was significantly higher than its
      true SPF.

PMID- 18713073
TI  - Studying the anti-tyrosinase effect of Arbutus andrachne L. extracts.
AB  - Arbutus andrachne L. is widely distributed in Jordan. Tyrosinase is the key
      enzyme in the biosynthesis of melanin. This preliminary study was carried out to
      assess the possible anti-tyrosinase activity of A. andrachne extracts. Arbutin,
      hydroquinone and kojic acid were selected as inhibitor standards. Five different
      extracts (chloroform, butanol, ethanol, methanol and water) were prepared from A.
      andrachne stems and their activities were compared with the selected tyrosinase
      inhibitors. IC(50) was measured for both, standard and plant extracts. Among the
      different extracts, the methanolic extract exhibited the highest anttyrosinase
      activity with an IC(50) value (1 mg mL(-1)). Furthermore, 9 mg A. andrachne
      methanolic extract showed 97.49% inhibition of tyrosinase activity. Arbutin,
      hydroquinone, beta-sitosterol and ursolic acid were identified in the different
      extracts of A. andrachne by thin layer chromatography (TLC) and isolated by
      preparative TLC from the methanolic and chloroform stem extracts, respectively.

PMID- 18713074
TI  - Irritancy ranking of 31 cleansers in the Indian market in a 24-h patch test.
AB  - Cleansing trends promise freshness, sensory and health benefits but may also be
      accompanied by an increase in soap-induced skin irritation. The aim of this study
      was to evaluate the irritant effect of 31 cleansers (28 bar soaps and 3 liquid
      cleansers) available in the Indian market. Eight percent w/v solutions of the
      soaps/cleansers were made and 30 microL of each of the solutions were applied to
      Finn chambers and occluded for 24 h along with distilled water (negative control)
      and 20% sodium dodecyl sulphate (SDS) as positive control. The sites were graded
      for erythema and scaling 30 min after removing the patches. The pH of each of the
      soap solutions was determined. Mean with SD and ANOVA (F-value) was computed
      separately for each soap/cleanser with respect to the two parameters, erythema
      and scaling. The total of the means for both the parameters, erythema and scaling
      was also computed. The cleansers were listed based on this total from the least
      irritant to the most irritant. The differences between soaps (F-value) was
      significant for erythema and scaling [erythema = 4.106 (P = 0.000); scaling =
      6.006 (P = 0.000)]. Cetaphil cleansing lotion had the lowest erythema score of
      0.25. Lowest scaling score of zero was recorded for Cetaphil cleansing lotion and
      Elovera moisturizing body wash. Aquasoft and Lifebuoy soaps had the highest
      erythema score of 2.13. Acnex had the highest scaling score of 1.75; Aquasoft,
      Hamam scrub bath soap and Naturepower sandal soaps were the next with a scaling
      score of 1.63. Cetaphil cleansing lotion, Aquaderm liquid soap, Dove bar soap and
      Elovera moisturizing body wash proved to be the least irritant cleansers with a
      total score of less than 1. The four most irritant soaps/cleansers had an average
      score of 3.65. The irritant potential of the majority of the cleansers fell
      between these extremes. The pH of all the soap/cleanser solutions was neutral to
      alkaline (pH 7-9) except that of Dove bar, Cetaphil cleansing lotion, Aquaderm
      liquid soap and Elovera moisturizing body wash which tested acidic (pH 5-6). The
      pH of the positive control--20% SDS, was acidic (pH 6). The difference in the
      irritancy potential between soaps/cleansers as determined by the 24-h patch test
      was significant. There were individual variations in the irritant potential of
      the soaps/cleansers in the volunteers, thus when the patient queries on what soap
      to use, it may be advisable to test each patient separately and educate him/her
      regarding the soaps/cleansers less likely to cause irritation. The limitations of
      the study was that it was single blind and non-randomized as all the 14 soap
      solutions were applied on 15 volunteers in the first panel and subsequently all
      the 17 soap solutions were applied on eight volunteers in the second panel.
      However, we could compare the irritant potential of 31 cleansers. The results of
      24-h patch testing of 31 soaps/cleansers in the Indian market in two panels of 14
      and 17 soaps/cleansers on 15 and eight volunteers, respectively, are presented.

PMID- 18713075
TI  - Development of chitosan-coated liposomes for sustained delivery of tamarind fruit
      pulp's extract to the skin.
AB  - In this study, chitosan-coated liposomes were developed. To entrap lyophilized
      tamarind extract containing alpha-hydroxy acids (AHAs) together with tartaric
      acid, the reverse phase evaporation method was used to obtain well-formed
      liposomes loaded with the extract. The highest entrapment efficiency of 68.3 +/-
      3.0% into the liposomes was obtained with liposomes consisting of
      phosphatidylcholine and cholesterol in a molar ratio of 2 : 1 after the extrusion
      process. The average particle size of the prepared liposomes was 158 +/- 26 nm
      showing a negative zeta potential of -6 mV. For the preparation of the chitosan
      coated liposomes, two selected independent parameters were varied: chitosan
      concentrations of 0.1, 0.5 and 1.0% w/v and volumes of the chitosan solutions of
      1, 2 and 3 mL, to study the effects of such parameters on the entrapment
      efficiency of the extract-loaded liposomes. Variation in the volumes of the
      chitosan solution did not affect the entrapment efficiency of the liposomes.
      However, the entrapment efficiency of the AHAs in the chitosan-coated liposomes
      significantly increased with increasing chitosan concentrations. The size of the
      chitosan-coated liposomes was in the range of 200-300 nm with a positive zeta
      potential in the range of 6-29 mV. An in vitro release study using dialysis
      technique was performed to evaluate the release profile of the tartaric acid from
      the chitosan-coated liposomes. The obtained results showed the effect of the
      chitosan-coated liposomes on the lower release rate and on the amount of tartaric
      acid in comparison with that of the uncoated liposomes. The study in an in vitro
      skin cell model indicated that the developed system could enhance the potential
      of tamarind's AHAs on the stimulation of human keratinocyte proliferation being
      two-fold higher than the solution of the tamarind extract.

PMID- 18713076
TI  - Analysis and quantification of parabens in cosmetic products by utilizing hollow
      fibre-supported liquid membrane and high performance liquid chromatography with
      ultraviolet detection.
AB  - A simple and direct method based on hollow fibre-supported liquid membrane
      (HFSLM) extraction and liquid chromatography equipped with a UV detector was
      developed for analysis and quantification of parabens in cosmetic products. The
      parabens analysed included methyl, ethyl, propyl, isobutyl and butyl paraben. The
      HFSLM extraction was carried out by employing di-n-hexyl ether as organic liquid
      that was immobilized in the hollow fibre membrane. The HFSLM extraction is
      simple, cheap, minimizes the use of solvents and uses disposable material. In an
      investigation of 11 paraben-containing cosmetic products, the levels of parabens
      (sum of all parabens in a product) ranged from 0.43% to 0.79% (w/w) for skin care
      products, 0.07-0.44% for hair fixing gels and 0.30-0.52% for soap solutions. The
      levels of individual parabens in individual cosmetic products ranged between
      0.03% and 0.42% w/w for skin care products, 0.07% and 0.26% w/w for hair fixing
      gels and between 0.11% and 0.34% w/w for soap solutions. Parabens were found in
      the highest concentrations in skin care products followed by soap solutions and
      the least amounts were found in hair fixing gels. Of the paraben-containing
      products tested, all of them contained methyl paraben and about 90% contained
      propyl paraben in addition to methyl paraben. One product contained all the
      parabens analysed.

PMID- 18713086
TI  - Mechanisms of airway hyperresponsiveness in asthma.
AB  - Airway hyperresponsiveness (AHR) is a fundamental abnormality in asthma. There
      are many potential factors contributing to the excessive airway response
      demonstrable on airway challenge. These range from abnormalities of airway smooth
      muscle, airway remodelling and airway inflammation to abnormalities in the neural
      control of airway calibre. None of these by themselves fully explains the
      abnormalities seen on the dose response curves of the asthmatic. In this review,
      the main mechanisms are described, together with recent evidence providing a
      pathway by which a number of these mechanisms may interact to cause AHR through
      abnormality in ventilation distribution and airway closure. There is now evidence
      for a close relationship between ventilation heterogeneity and AHR which could be
      exploited clinically.

PMID- 18713087
TI  - Recombinant human erythropoietin reduces epithelial cell apoptosis and attenuates
      bleomycin-induced pneumonitis in mice.
AB  - BACKGROUND AND OBJECTIVE: Erythropoietin (EPO) has recently been demonstrated to
      have a tissue protective role by acting as an anti-apoptotic agent in various
      tissues, such as brain, spinal cord, heart and kidney. The purpose of this study
      was to determine whether human recombinant EPO reduces epithelial cell apoptosis
      and attenuates bleomycin-induced pneumonitis in mice. METHODS: Bleomycin was
      instilled intratracheally into C57BL/6 mice. Recombinant human EPO or saline was
      injected intraperitoneally, daily from day 5 to day 13 after bleomycin
      instillation. RESULTS: EPO receptor was expressed in bronchiolar and alveolar
      type II cells. At 14 days after instillation, the number of terminal uridine
      deoxynucleotidyl transferase nick end-labelled positive cells in the lung was
      decreased, and the histological degree of inflammation and fibrosis was
      attenuated in mice injected with EPO compared with controls. Expression of
      phosphorylated Akt and Erk, which are thought to mediate the survival signalling
      pathway induced by EPO, tended to be increased in lung tissues from mice treated
      with EPO compared with those from mice treated with saline after bleomycin
      instillation. CONCLUSIONS: As it is likely that EPO protects epithelial cells
      from injury and apoptosis, EPO administration could be a potential therapeutic
      strategy for the prevention of lung injury.

PMID- 18713088
TI  - Preventive effects of edaravone, a free radical scavenger, on lipopolysaccharide
      induced lung injury in mice.
AB  - BACKGROUND AND OBJECTIVE: Reactive oxygen species (ROS) play an important role in
      the pathogenesis of acute lung injury (ALI) and pulmonary fibrosis. It was
      hypothesized that edaravone, a free radical scavenger, would be able to attenuate
      LPS-induced lung injury in mice by decreasing oxidative stress. METHODS: For the
      in vivo experiments, lung injury was induced in female BALB/c mice by the
      intranasal instillation of LPS. Edaravone was given by intraperitoneal
      administration 1 h before the LPS challenge. For the in vitro experiments, MH-S
      cells (murine alveolar macrophage cell line) were exposed to edaravone, followed
      by stimulation with LPS. RESULTS: In the LPS-induced ALI mouse model, the
      administration of edaravone attenuated cellular infiltration into and the
      concentrations of albumin, IL-6, tumour necrosis factor-alpha, keratinocyte
      derived chemokine and macrophage inflammatory protein-2 in BAL fluid. In
      addition, the in vitro studies showed that the elevated IL-6 secretion from MH-S
      cells in response to LPS was significantly attenuated by co-incubation with
      edaravone. CONCLUSIONS: In an experimental murine model, a free radical scavenger
      may prevent ALI via repression of pro-inflammatory cytokine production by lung
      macrophages.

PMID- 18713089
TI  - Bosentan therapy in patients with pulmonary arterial hypertension: the
      relationship between improvements in 6 minute walk distance and quality of life.
AB  - BACKGROUND AND OBJECTIVE: Bosentan, an oral, dual endothelin receptor antagonist,
      significantly improves functional status, haemodynamic measures and survival in
      patients with pulmonary arterial hypertension (PAH). However, there are limited
      data on the effect of bosentan on quality of life (QOL) and its relationship to
      changes in functional status, as measured by the 6 minute walk distance (6MWD).
      METHODS: A retrospective analysis was performed of a large, open-label,
      multicentre trial (VITAL) of bosentan in patients with PAH. Data for 6MWD were
      collected at baseline, 3 or 6 months and these results were correlated with QOL
      measurements collected as part of the assessment of patients enrolled in the
      trial. RESULTS: Sixty-nine patients with PAH (mean age 52 years) who were
      enrolled in the trial had valid QOL (SF-36) measurements and 6MWD data that could
      be retrieved from clinical notes. At 3 and 6 months, bosentan therapy improved
      6MWD compared with baseline (49.5 m and 47.2 m, respectively, P < 0.001) as well
      as QOL domains, with a significant correlation between these two markers on cross
      sectional analysis. However, there was a poor relationship when comparing changes
      in 6MWD with changes in QOL, in response to therapy. CONCLUSION: Bosentan therapy
      was associated with improvements in QOL and 6MWD for at least 6 months. At all
      measured time points, there was a close correlation between 6MWD and most QOL
      domains. QOL is an important parameter and should be considered as part of the
      standard assessment for any trial investigating therapy in PAH.

PMID- 18713090
TI  - Association between angiotensin-converting enzyme gene polymorphisms and exercise
      performance in patients with COPD.
AB  - BACKGROUND AND OBJECTIVE: Recent studies have shown that polymorphisms of the
      angiotensin-converting enzyme (ACE) gene are closely associated with pulmonary
      disorders. The ACE gene is involved in the regulation of inflammatory reactions
      to lung injury, respiratory drive, erythropoiesis and tissue oxygenation. The
      hypothesis for this study was that the ACE gene may be associated with the
      ventilatory response to exercise and the aerobic work efficiency of skeletal
      muscle in patients with COPD. METHODS: Sixty-one Chinese Han COPD patients and 57
      healthy control subjects performed incremental cardiopulmonary exercise testing
      on a cycle ergometer. ACE genotypes were determined using PCR amplification.
      RESULTS: Resting lung function and blood gas index were not significantly
      different among the three ACE genotype COPD groups. Similarly, there were no
      significant differences in AT, maximal O(2) uptake, maximal O(2) pulse, maximal
      dyspnoea index, ventilatory response (DeltaVE/DeltaVCO(2)), O(2) cost of
      ventilation (VO(2)/W/VE), end-tidal partial pressure of carbon dioxide at maximal
      exercise and maximal SaO(2) among the three ACE genotype COPD patients. Maximal
      work load and aerobic work efficiency were higher in the COPD group with the II
      genotype than in those with the ID or DD genotype. There were no significant
      differences in resting lung function and cardiopulmonary exercise testing
      parameters among the three ACE genotype control groups. CONCLUSIONS: The ACE gene
      may be involved in the regulation of skeletal muscle aerobic work efficiency, but
      is not associated with the ventilatory responses to exercise in COPD patients.

PMID- 18713091
TI  - The efficacy and applicability of a pulmonary rehabilitation programme for
      patients with COPD in a secondary-care community hospital.
AB  - BACKGROUND AND OBJECTIVE: Pulmonary rehabilitation is known to have beneficial
      effects in COPD patients. This study aimed to assess the applicability and
      efficacy of a pulmonary rehabilitation programme in a community hospital lacking
      specialist pulmonary rehabilitation services. METHODS: This randomized,
      controlled, prospective study included a total of 78 patients. Questionnaires
      were used to collect data on sociodemographic characteristics, respiratory
      function tests, the Modified Medical Research Council dyspnoea scale, 6MWD, the
      Short Form-36 (SF-36) quality of life scale, the Hospital Anxiety and Depression
      Scale (HADS) and the St George's Respiratory Questionnaire (SGRQ). The
      experimental group underwent a pulmonary rehabilitation programme while the
      control group did not participate. The first, second and third month measurements
      for all parameters were compared between the two groups. RESULTS: No significant
      differences in pulmonary function tests or dyspnoea scale (P > 0.05) were
      observed between the two groups. Significant differences were observed in the
      6MWD measurements at the third month (P < 0.05), as well as in the SF-36 quality
      of life scale, SGRQ and HADS measurements at the second and third months (P <
      0.01). CONCLUSIONS: Short-term pulmonary rehabilitation had a positive impact on
      exercise capacity and quality of life of patients with COPD, irrespective of
      FEV(1). This study demonstrated the efficacy of a pulmonary rehabilitation
      programme in a secondary care hospital not staffed by a specialist pulmonary
      rehabilitation group.

PMID- 18713092
TI  - Efficacy of the 'tennis ball technique' versus nCPAP in the management of
      position-dependent obstructive sleep apnoea syndrome.
AB  - BACKGROUND AND OBJECTIVE: Avoidance of sleep in the supine position is
      recommended in the management of position-dependent OSA hypopnoea syndrome
      (OSAHS). Our aim was to evaluate the efficacy of a thoracic anti-supine band
      (TASB), designed to mimic the so-called 'tennis ball technique', compared with
      nasal CPAP (nCPAP). METHODS: Twenty adults with mild to moderately severe
      position-dependent OSAHS (mean AHI +/- SD) 22.7 +/- 12.0/H (range 6.0-51.2); AHI
      supine, 59.6 +/- 27.5/H, were included in a randomized cross-over trial. Portable
      sleep studies were undertaken at baseline and after 1 month on each treatment. A
      successful treatment outcome was defined as AHI <or= 10/H. RESULTS: Mean AHI was
      12.0 +/- 14.5/H with the TASB and 4.9 +/- 3.9/H with nCPAP (P = 0.02; 95%
      confidence interval for the difference: -13.1 to -1.0). With the TASB, treatment
      'success' was achieved in 13/18 subjects, whereas 'success' was achieved in 16/18
      subjects using nCPAP (P = 0.004). In the two subjects with baseline AHI < 10/H,
      AHI remained below 10 for both therapies. The TASB successfully reduced time
      spent in the supine position. Mean percentage supine sleep time was 6.3 +/- 5.9%
      with the TASB, and 35.4 +/- 34.1% with nCPAP (P < 0.001). No significant
      differences in sleep efficiency or subjective responses were observed between
      treatments. CONCLUSIONS: Control of body position during sleep using an anti
      supine device mimicking the so-called 'tennis ball technique' provides benefit in
      the management of position-dependent OSAHS in subjects who meet strict inclusion
      criteria. The overall improvement is, however, less than for nCPAP.

PMID- 18713093
TI  - Environmental dust granulometry and microbial load in the presence of tobacco
      smoke.
AB  - BACKGROUND AND OBJECTIVE: Several studies describe damage from passive smoking in
      humans. However, it is not clearly understood how different chemical and physical
      components relate to mechanisms of damage. This investigation was focused on the
      particulate phase of environmental cigarette smoke. The size of particles is very
      important in the inhalation process and subsequent deposition of particles in the
      airways. METHODS: The granulometry of suspended dust and bacterial particles was
      studied in a 120-m(3) no-smoking room during and after the smoking of one
      cigarette in ten separate experiments. Granulometry was assessed by a six-channel
      particle counter. Suspended microbial load was evaluated by a surface air system.
      The sedimented bacterial load was evaluated by the air microbial index technique,
      which expresses the total number of microorganisms settling on a Petri plate
      under gravity. RESULTS: The number of large particles increased during the first
      minute of smoking, and then decreased to basal levels. The number of medium-sized
      particles increased during the first 10 min of cigarette smoking, and then
      decreased to basal levels. The number of small particles increased over the whole
      experimental period. Bacterial and mycotic load decreased during and up to 60 min
      after cigarette smoking. Gram-positive cocci did not decrease, while chromogenous
      bacteria and mycetes decreased at 30 min. There was an increase in the numbers of
      sedimented bacteria and mycetes at 60 min, a decrease at 120 min and
      stabilization at 180 min. CONCLUSIONS: Smoking of tobacco accelerates the
      sedimentation of larger agglomerates of mean-sized smoke particles and bacteria,
      which may be re-suspended by the movement of people in the room and consequently
      inhaled.

PMID- 18713094
TI  - Comparison of severity scoring systems A-DROP and CURB-65 for community-acquired
      pneumonia.
AB  - BACKGROUND AND OBJECTIVE: The initial assessment of the severity of community
      acquired pneumonia (CAP) is important for patient management. The Japanese
      Respiratory Society (JRS) has proposed a 6-point scale (0-5) to assess the
      clinical severity of CAP. The A-DROP scoring system assesses the following
      parameters: (i) Age (male >or= 70 years, female >or= 75 years); (ii) Dehydration
      (blood urea nitrogen (BUN) >or= 210 mg/L); (iii) Respiratory failure (SaO(2) <or=
      90% or PaO(2) <or= 60 mm Hg); (iv) Orientation disturbance (confusion); and (v)
      low blood Pressure (systolic blood pressure <or= 90 mm Hg). A-DROP is a modified
      version of CURB-65 (confusion, BUN > 7 mmol/L (200 mg/L), respiratory rate >or=
      30/min, low blood pressure (diastolic <or= 60 mm Hg or systolic < 90 mm Hg, and
      age >or= 65 years) proposed by the British Thoracic Society. However, validation
      of A-DROP has not been attempted nor has it been compared with CURB-65. The aim
      of this study was to confirm that A-DROP is equivalent to CURB-65 for predicting
      severity of CAP. METHODS: A retrospective observational study was conducted of
      patients with CAP hospitalized at a single centre between November 2005 and
      January 2007. The 30-day mortality after admission was compared following
      assessment of severity using the A-DROP and CURB-65 scoring systems. RESULTS:
      Three-hundred and twenty-nine patients were evaluated. The areas under the
      receiver operating characteristic curves were 0.846 (95% confidence interval
      (CI): 0.790-0.903) and 0.835 (95% CI: 0.763-0.908) for A-DROP and CURB-65,
      respectively. CONCLUSION: The JRS A-DROP can be used to assess severity of CAP,
      and gives similar results to CURB-65.

PMID- 18713095
TI  - A competency-based test of bronchoscopic knowledge using the Essential
      Bronchoscopist: an initial concept study.
AB  - BACKGROUND AND OBJECTIVE: Competency-based training and assessment are
      increasingly replacing the traditional structure- and process-based model of
      medical education. The web-based Essential Bronchoscopist (EB) is an open access,
      laddered, competency-based curriculum of question-answer sets pertaining to basic
      bronchoscopic knowledge, accessible in five languages. The purpose of this study
      was to use consensus to evaluate whether question-answer sets (items) from the EB
      could provide material from which to devise competency-based tests of
      bronchoscopic knowledge that could be used in countries with different health
      care environments. METHODS: Ten junior and five senior bronchoscopists in
      Argentina and the USA were asked to identify the material in each of the 186
      items of the EB as either 'not necessary', 'necessary' or 'absolutely necessary'
      for inclusion in a competency-based test of bronchoscopic knowledge. The kappa
      statistic was used to analyse inter-rater agreement. RESULTS: More than 80% of
      the 30 participants rated 150 of 186 items as necessary or absolutely necessary.
      Seventy items were rated as absolutely necessary by more than 50% of participants
      and as necessary or absolutely necessary by more than 90%. There was no
      statistically significant difference between items selected, based on level of
      training or environment of practice. CONCLUSION: Consensus among junior and
      senior bronchoscopists from two culturally different health-care environments
      demonstrated that question-answer sets from the EB can be used to provide
      material for competency-based tests of bronchoscopic knowledge.

PMID- 18713096
TI  - Primary pulmonary synovial sarcoma, a rare primary lung neoplasm: two case
      reports and review of the current literature.
AB  - This report describes the clinical, histological and immunohistochemical features
      of two patients with primary pulmonary synovial sarcoma in the context of the
      literature. Chest pain, cough, haemoptysis and an enlarging pleural-based mass
      are the main clinical manifestations. Diagnosis depends on identifying
      epithelioid or spindle cells microscopically and on immunohistochemistry showing
      positivity for cytokeratin and vimentin and epithelial membrane antigen stains.
      Surgical excision is the main treatment approach.

PMID- 18713097
TI  - Solitary pleural plasmacytomas manifested as a massive pleural effusion without
      evidence of monoclonal gammopathy.
AB  - The majority of extramedullary plasmacytomas involve the upper respiratory tract
      but only a few are associated with serum monoclonal gammopathy. Most
      extramedullary plasmacytomas respond to local radiotherapy and have a better
      prognosis than multiple myeloma. Solitary plasmacytomas, involving the pleura,
      are very rare. This case report describes a patient with a solitary
      extramedullary plasmacytoma involving the pleura, and no evidence of serum, urine
      or pleural fluid paraproteins. Diagnosis was made by strongly positive
      immunohistochemical stains with CD38, CD138 and MUM-1 of the pleural tumour. The
      response to both radiotherapy and chemotherapy was poor and the patient died
      shortly after diagnosis.

PMID- 18713101
TI  - Should we attempt to detect bacteria in red blood cells?

PMID- 18713102
TI  - Blood supply safety: an NHLBI perspective.

PMID- 18713103
TI  - Transfusion medicine illustrated: blocked D phenomenon.

PMID- 18713104
TI  - Sporadic leukoreduction filter failure during red blood cell component
      preparation: beware of rapid filtration.

PMID- 18713105
TI  - Frequencies of the JKnull (IVS5-1g>a) allele in Taiwanese, Fujian, Filipino, and
      Indonesian populations.

PMID- 18713107
TI  - Partnerships for blood safety in Africa: the U.S. President's Emergency Plan for
      AIDS Relief.

PMID- 18713108
TI  - Evaluating red cell recoveries in clinical trials: where should we set the bar?

PMID- 18713109
TI  - Transfusion medicine illustrated: images in transfusion medicine.

PMID- 18713110
TI  - The role of noninferiority designs in clinical research.

PMID- 18713111
TI  - Blood safety in Sub-Saharan Africa: a multi-factorial problem.
AB  - Although the World Health Organization (WHO) has set targets for safe blood by
      2012, Sub-Saharan Africa remains confronted with multi-factorial issues that
      compromise blood safety in most countries of the region. Some of these include
      the development and implementation of national policies for transfusion, the
      recruitment of voluntary and unpaid donors, proper screening of collected blood
      as well as a strategy for its rational use in a setting already plagued by a high
      prevalence of blood-borne agents, poverty, and sometimes organizational deficits.
      Furthermore, the organization of hemovigilance, as well as quality systems that
      could monitor transfusion practices is lacking in these settings. There is no
      funding and global improvement of blood safety has to be cheap to be feasible.
      Specific solutions for the African continent need to be developed and
      implemented. This paper examines the current status and difficulties of blood
      safety in Africa and reviews available data on transfusion medicine in the
      region.

PMID- 18713112
TI  - A letter from Kenya.

PMID- 18713113
TI  - Letters from Africa.

PMID- 18713114
TI  - A letter from South Africa.

PMID- 18713115
TI  - A letter from Rwanda.

PMID- 18713116
TI  - A letter from Tanzania.

PMID- 18713117
TI  - A letter from Mozambique.

PMID- 18713118
TI  - The CARI guidelines. Vascular access surveillance.

PMID- 18713119
TI  - The CARI guidelines. Pharmacological approaches to preventing vascular access
      failure.

PMID- 18713120
TI  - The CARI guidelines. ANCA serology in the diagnosis and management of ANCA
      associated renal vasculitis.

PMID- 18713121
TI  - The CARI guidelines. Induction and maintenance therapy in ANCA-associated
      systemic vasculitis.

PMID- 18713122
TI  - The CARI guidelines. Renal transplantation.

PMID- 18713123
TI  - The CARI guidelines. Biochemical and haematological targets. Haemoglobin.

PMID- 18713127
TI  - The German guideline for the management of hepatitis B virus infection: short
      version.

PMID- 18713128
TI  - Vacuum assisted closure: recommendations for use. A consensus document.

PMID- 18713129
TI  - Multitrophic interactions in the rhizosphere Rhizosphere microbiology: at the
      interface of many disciplines and expertises.

PMID- 18713130
TI  - Searching for the Achilles' heel of melanoma cells: new treatment modalities.

PMID- 18713131
TI  - The ARFul truth about melanoma susceptibility genes.

PMID- 18713132
TI  - Ribosomes and p53 - a new KIT for skin darkening.

PMID- 18713133
TI  - Bilateral metabolic cataracts in 10-yr-old boy with newly diagnosed type 1
      diabetes mellitus.
AB  - Classic symptoms of diabetes mellitus in childhood prompting parents to seek
      medical attention include polydipsia, polyuria, polyphagia, weight loss and
      kussmal breathing. Cataracts with juvenile diabetes usually occur in patients
      with long-standing, poorly controlled diabetes (1, 2). We describe a child in
      whom the acute loss of vision secondary to lenticular opacities was the initial
      sign of insulin-dependent diabetes mellitus.

PMID- 18713134
TI  - Screening frequency for celiac disease and autoimmune thyroiditis in children and
      adolescents with type 1 diabetes mellitus--data from a German/Austrian
      multicentre survey.
AB  - OBJECTIVE: Type 1 diabetes mellitus (T1DM) is associated with other autoimmune
      diseases such as celiac disease (CD) and Hashimoto thyroiditis. The aim of this
      study was to evaluate the screening frequency for CD and thyroid antibodies in a
      multicentre survey. METHODS: The Diabetes Patienten Verlaufsdokumentationssystem
      (DPV) initiative is based on standardized, prospective, multicentre documentation
      in children and adolescents with diabetes. Data from 31,104 patients <18 yr of
      age (52% males, mean age 13.1 yr) with T1DM from 177 paediatric centres in
      Germany and Austria from 1995 until 2007 were analysed. RESULTS: Of 31,104
      patients, 16,994 patients (55%) were screened at least once for CD. In 1995, 44%
      of the patients were screened for CD compared with 68.6% in 2006. Annual
      screening for CD has also increased (11.9% in 1995 compared with 43.6% in 2006).
      Eleven per cent of the patients had positive antibodies for CD. Patients with
      positive antibodies were significantly younger at diabetes onset and had a
      significantly longer duration of diabetes (p < 0.001). Compared with screening
      for CD, screening for thyroid antibodies was performed more frequently (at least
      once in 62% of the patients). Fifteen per cent of the patients had positive
      thyroid antibodies. Screening for thyroid antibodies also increased from 62.6 to
      72.9%, and annual screening frequency increased from 15.9 to 48.9%. CONCLUSION:
      Screening for associated autoimmune diseases in children with T1DM has increased
      during the past decade. Eleven per cent of the patients had positive CD-specific
      antibodies, and 15% had positive thyroid antibodies. Screening for thyroid
      antibodies is performed more frequently than screening for CD.

PMID- 18713135
TI  - Short-term UV exposure of sunbathers at a Mediterranean Sea site.
AB  - The aim of this study was to investigate whether systematic differences in solar
      UV exposure on a specific anatomical site (chest) exist among three groups of
      Italian sunbathers: healthy subjects (suntanned and non-suntanned individuals)
      and subjects affected by abnormally high sensitivity to solar exposure. A second
      aim of the study was to search for a possible relation among biological markers
      of individual response to UV exposure (such as skin colorimetric parameters, skin
      temperature and changes in free radical amounts [FR] in the blood) and
      photosensitivity. FR in the blood were analyzed because of their possible
      influence on UV carcinogenesis. Measurements of ambient doses (i.e. incident
      erythemally weighted irradiance on a horizontal surface over a specified period
      of time) and erythemally effective UV dose received by an anatomical site (here
      called personal dose or exposure on a specific anatomical site) were
      investigated. Personal doses received by the chest were determined using
      polysulfone dosimetry. Exposure Ratio (ER), defined as the ratio between the
      personal dose and the corresponding ambient dose during the same exposure period,
      was then calculated. Measuring of skin color in the Commission Internationale de
      l'Eclairage L (luminance), a (redness), b (yellowness) system and skin
      temperature were also carried out on the inner upper arm (nonexposed skin site)
      and on the chest. It was found that the median value of ER was 0.20 (min: 0.09
      and max: 0.34) for suntanned individuals, it was 0.17 (min: 0.13 and max: 0.42)
      for non-suntanned individuals and it was 0.19 (min: 0.14 and max: 0.34) for
      photosensitive individuals. There were no significant differences across the
      groups in their median ER scores. In addition, the statistical analysis showed
      that L on the exposed site before exposure demonstrated consistently higher
      median scores after exposure in all groups. The b value after exposure was
      significantly lower than before exposure in all participants, while no
      significant differences for a were observed before or after exposure between or
      within the groups. Our findings suggest that photodermatoses are not
      significantly related to ER and to the changes in biological markers due to too
      short-term UV exposure.

PMID- 18713136
TI  - Clinical features and outcomes of Legionnaires' disease in solid organ transplant
      recipients.
AB  - We identified 14 cases of Legionnaires' disease occurring in 2946 solid organ
      transplant recipients from 1985 to 2007. Most cases were sporadic and community
      acquired. The recent introduction of the urinary antigen test has accelerated
      diagnosis and allows prompt institution of adequate therapy. The overall
      mortality rate in our series was 14.3%.

PMID- 18713137
TI  - An aspergillotic aneurysm of the internal carotid artery following allogeneic
      bone marrow transplantation: successful management with catheter coil
      embolization and long-term antifungal agents.
AB  - We report a case of a mycotic aneurysm of the internal carotid artery and
      cerebral hemorrhagic infarction resulting from Aspergillus middle ear infection
      in a patient with severe aplastic anemia who received unrelated bone marrow
      transplantation. Although a mycotic aneurysm is a rare complication, and most
      often fatal, the patient was successfully treated with catheter coil embolization
      of the internal carotid artery and long-term systemic antifungal therapy. This
      case emphasizes the need for the rapid diagnosis of potential fungal involvement
      of the vascular system and suggests the necessity for aggressive treatment, such
      as with the modality illustrated in this case.

PMID- 18713138
TI  - Acanthamoeba infection in a patient with chronic graft-versus-host disease
      occurring during treatment with voriconazole.
AB  - We report a case of disseminated infection with Acanthamoeba in a patient with
      graft-versus-host disease after hematopoietic stem cell transplant (HSCT) for
      acute lymphocytic leukemia. The infection involved the brain, skin, and lungs and
      occurred despite treatment with voriconazole for mold prophylaxis, and did not
      respond to treatment with multiple other agents reported to have activity against
      Acanthamoeba. To our knowledge, infection with Acanthamoeba has been reported in
      4 other patients after HSCT or bone marrow transplant, and our case is the first
      to be diagnosed ante-mortem.

PMID- 18713139
TI  - An approach to the patient with urticaria.
AB  - Patients with urticaria make up a large proportion of the referrals to allergy
      clinics. There are many causes of urticaria and it is the clinical history which
      is most important when attempting to identify potential causes; however,
      urticaria is very often idiopathic. In a small minority of patients urticaria may
      be a symptom of a serious underlying medical illness or the allergic symptoms may
      progress to cause systemic reactions, and it is important to identify these
      patients and to remember that severe urticaria is a distressing and disabling
      condition. This review will discuss classification, investigation and treatment
      of urticaria and will consider some of the more unusual types of urticaria that
      may be encountered in the out-patient clinic.

PMID- 18713140
TI  - Translational mini-review series on the immunogenetics of gut disease:
      immunogenetics of coeliac disease.
AB  - Recent advances in immunological and genetic research in coeliac disease provide
      new and complementary insights into the immune response driving this chronic
      intestinal inflammatory disorder. Both approaches confirm the central importance
      of T cell-mediated immune responses to disease pathogenesis and have further
      begun to highlight other relevant components of the mucosal immune system,
      including innate immunity and the control of lymphocyte trafficking to the
      mucosa. In the last year, the first genome wide association study in celiac
      disease led to the identification of multiple new risk variants. These risk
      regions implicate genes involved in the immune system. Overlap with autoimmune
      diseases is striking with several of these regions being shown to confer
      susceptibility to other chronic immune-mediated diseases, particularly type 1
      diabetes.

PMID- 18713142
TI  - Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced
      arthritis in mice.
AB  - Mesenchymal stem cells (MSCs) have the inherent ability to migrate to multiple
      organs and to exert immunosuppressive activity. The aim of this study was to
      investigate the anti-arthritogenic effects of interleukin (IL)-10-transduced MSCs
      (IL-10-MSC) on the development of inflammatory arthritis. DBA/1 mice were
      immunized with type II collagen (CII) to induce inflammatory arthritis and then
      injected weekly three times with IL-10-MSCs 21 days after primary immunization.
      Control mice received vehicle or MSCs alone. Serum anti-CII antibody and T cell
      response to CII were determined. The results showed that cultured IL-10-MSCs were
      able to secrete high amounts of IL-10 in vitro. Injection of IL-10-MSCs decreased
      the severity of arthritis significantly. However, there was no difference in
      arthritis severity between mice treated with MSC and vehicle alone. Anti-CII
      antibody titres in the sera and T cell proliferative response to CII in lymph
      node cells were decreased significantly in mice treated with IL-10-MSCs compared
      with vehicle-treated mice. Serum IL-6 level was also decreased by the
      administration of IL-10-MSCs. In contrast, spleen cells of IL-10-MSC-treated mice
      produced higher amounts of IL-4 than those of control mice. Interestingly,
      although not as potent as IL-10-MSCs, injection of naive MSCs alone decreased
      serum levels of IL-6 and anti-CII antibody, while increasing IL-4 production from
      cultured splenic cells. Taken together, systemic administration of genetically
      modified MSCs overexpressing IL-10 inhibits experimental arthritis not only by
      suppressing autoimmune response to CII but also by regulating cytokine
      production, and thus would be a new strategy for treating rheumatoid arthritis.

PMID- 18713141
TI  - Leishmania surface protein gp63 binds directly to human natural killer cells and
      inhibits proliferation.
AB  - Natural killer (NK) cells contribute to immunity as the first line of defence in
      numerous infections by early cytokine secretion and cytotoxicity. In Leishmania
      infection, NK cells contribute with interferon-gamma and may assist in directing
      the immune response towards T helper type 1, which is essential for successful
      control of the parasites. Thus, NK cells may play an important role in both
      resistance and control of the infection. However, during Leishmania infection NK
      cells show signs of suppression. To explore the reason for this suppression, we
      exposed naive and interleukin (IL)-2 activated NK cells directly to promastigotes
      of Leishmania major in vitro. As a rapid consequence of contact between naive NK
      cells and promastigotes, expression of NK cell receptors show significant
      changes. We identify one of the major surface molecules of promastigotes,
      glycoprotein (gp) 63, as an important agent for these suppressive effects by
      using promastigotes of a gp63ko strain of L. major. Furthermore, proliferation of
      IL-2-activated purified NK cells is suppressed after exposure to the wild-type
      but not to gp63ko promastigotes. However, gp63ko L. major induced no NK cell
      proliferation when NK cells were co-cultured with peripheral blood mononuclear
      cells populations such as CD14(+) monocytes or T cells.

PMID- 18713145
TI  - Alternate method to secure the aorta for organ perfusion in donation after
      cardiac death donors.

PMID- 18713144
TI  - Effect of different induction strategies on effector, regulatory and memory
      lymphocyte sub-populations in clinical islet transplantation.
AB  - This prospective study assessed lymphocyte subsets in the peripheral blood of 42
      islet allograft recipients using flow cytometry from 2 weeks and up to 2 years
      post-transplantation. Subjects received daclizumab (n = 16), Thymoglobulin (n =
      12) or alemtuzumab (n = 14). Alemtuzumab was associated with an early (within 1
      month) and transient (up to 6 months) increase in the frequency of CD3(+) CD4(+)
      Foxp3(+) T cells, while daclizumab induced a near complete loss of these cells (P
      <or= 0.001). The frequency of memory CD4(+) T cells was increased following
      depleting immunosuppression induction with either Thymoglobulin or alemtuzumab (P
      <or= 0.05), but remained unchanged while using daclizumab. Alemtuzumab induction
      resulted in a significant loss of memory B lymphocytes when compared with the
      other induction groups (P <or= 0.001). While the clinical significance of these
      findings remains to be fully determined, the observed altered balance between
      effector, regulatory and memory cells suggests that the immune status of patients
      will be affected according to the induction strategy chosen.

PMID- 18713146
TI  - Rapamycin in islet transplantation: friend or foe?
AB  - The Edmonton protocol was undoubtedly a major step forward in the history of
      islet transplantation. Its immunosuppression regimen was largely based on the
      mTOR inhibitor rapamycin (sirolimus), which remains the most frequently used
      immunosuppressive drug in clinical islet transplant protocols. As time reveals
      the somewhat disappointing long-term results achieved with the Edmonton protocol,
      a number of publications have appeared addressing the potential beneficial or
      deleterious role of rapamycin on islet cell engraftment, function survival and
      regeneration, as well as on its side-effects in human subjects. This paper
      reviews the sometimes contradictory evidence on the impact of rapamycin in islet
      transplantation.

PMID- 18713147
TI  - Minimization protocols in pancreas transplantation.
AB  - Diagnosis of immunologic injury (acute and chronic) is much more difficult in
      pancreas transplants when compared with transplants of other organs. Currently,
      the immunosuppressive regimen for induction involves calcineurin inhibitors
      (CNI), antimetabolites and corticosteroids (Cs). This strong and nonspecific
      regimen does not take into consideration pancreas specificities (i.e. the need to
      avoid diabetogenic compounds). For obvious reasons, CNI might be calling for
      review, if permanently indicated in recipients of solitary pancreas with mild
      renal dysfunction. CNI as well as corticosteroids may induce hyperglycemia and
      contribute to differential diagnosis of a rejection process. However, in spite of
      the benefits accruing from withdrawal of above immunosuppressive agents,
      minimization or avoidance of these drugs could be dangerous and may end up with
      graft loss (i.e. antibody-mediated process). Long-term results of pancreas
      transplantation are now achieving comparable survival rates similar to the
      transplant of traditional organs such as kidney and liver. As a consequence, the
      physicians' objectives are to prolong the patient's quality of life and organ
      function as long as possible. Weaning strategies in regard to CNI and steroids
      are tested. Sirolimus, everolimus, CTLA-4 Ig, etc, are agents known to be either
      both nonnephrotoxic and nondiabetogenic or less so when compared with CNI. Their
      impact on pancreas transplantation is beginning to be evaluated. Large randomized
      trials in all pancreas categories, with long-term clinical and histologic
      results, are mandatory to establish new guidelines for immunosuppressive regimens
      for pancreas transplantation.

PMID- 18713148
TI  - Liver transplantation for primary and metastatic liver cancers.
AB  - Liver transplantation for hepatic malignancies has emerged as a well-documented
      and proven treatment modality. However, early unsatisfactory results emphasized
      that only a highly selected patient population would benefit from
      transplantation. Currently, 15% of all liver transplants performed are for
      hepatocellular carcinoma (HCC). There is no controversy about the fact that liver
      transplantation for HCC in the adult population yields good results for patients
      whose tumour masses do not exceed the Milan criteria. It remains to be determined
      whether patients with more extensive tumours can be reliably selected to benefit
      from the procedure. In patients with small HCC at an early stage and preserved
      liver function, liver resection provides an alternative to transplant. Liver
      resection may offer similar survival results to orthotopic liver transplantation
      (OLT) in the short term, and does not carry the long-term effects of
      immunosuppression; however, long-term and disease-free survival favours liver
      transplantation. Very promising results have been obtained for cholangiocarcinoma
      treated by aggressive combination therapies, including chemo- and radiotherapy
      followed by OLT. Survival rate in these selected patients can approach that of
      patients with cholestatic liver disease, and the role of transplantation now
      requires re-evaluation. Similarly, hepatoblastoma is an excellent indication in
      paediatric patients with unresectable or recurrent tumours. Epithelioid
      hemangioendothelioma is also an appropriate indication for liver transplantation,
      even in the presence of extrahepatic metastases, unlike angiosarcoma which is
      associated with a very poor survival and considered as a contraindication. And
      finally for metastatic liver disease from neuroendocrine tumours, liver
      transplantation can result in long-term survival and even cure in well selected
      patients. Conversely, the value of transplantation for colorectal liver
      metastases (currently a contraindication) requires further evaluation by well
      designed trials.

PMID- 18713149
TI  - The many faces of the genetics contribution to temporomandibular joint disorder.
AB  - OBJECTIVES: Review the literature on candidate genes for temporomandibular joint
      disorder (TMD). Setting and Sample Population - Literature review. MATERIALS AND
      METHODS: Two basic approaches were used to obtain literature in any language
      regarding genes and TMD. First, Medline, Embase, and Science Citation Index
      databases were searched using the keywords 'temporomandibular joint disorder' and
      'temporomandibular joint dysfunction' for studies published from 1966 to 2007.
      Then, the references list of the studies obtained in the database was also
      considered. RESULTS: Candidate genes for TMD include genes for individual
      variations in pain perception, gender and ethnicity, proinflammatory cytokines,
      female hormones, breakdown of extracellular matrix, and syndromic forms of TMD.
      CONCLUSION: Most of the studies on genetic variation contributing to TMD are
      approaching the disease mainly from an immune-inflammatory perspective. Recent
      investigations of the genetic variables which may predict identifiable levels of
      pain perception may uncover new approaches to our traditional treatment
      modalities for the chronic pain patient.

PMID- 18713150
TI  - Effect of chlorhexidine mouth rinse on Streptococci counts of tooth-tissue-borne
      palatal expander biofilm.
AB  - OBJECTIVES: To assess total Streptococci (TS) counts and biofilm mass over tooth
      tissue-borne palatal expander (TTBPE), as well as the effect of chlorhexidine
      (CHX) mouth rinse on these variables. DESIGN: A cross-sectional study design
      employed clinical procedures and laboratorial techniques. SETTING AND SAMPLE
      POPULATION: Patients who had TTBPE removal indicated were divided into two
      groups: a CHX group (n = 26) in which three times a day of 0.2% CHX digluconate
      mouth rinses were prescribed 7 days before TTBPE removal; and a control (CON)
      group (n = 25) in which no antimicrobial treatment was applied. EXPERIMENTAL
      VARIABLE: 'Gender', 'Age', and 'TTBPE wear time' were recorded. After TTBPE
      removal, biofilm mass was determined by the difference between (TTBPE + biofilm)
      and (TTBPE only) masses. TS counts were determined by biofilm suspension followed
      by progressive dilutions and culture on Mitis Salivarius agar with incubation at
      37 degrees C for 72 h. OUTCOME MEASURE: Biofilm mass (mg) and Colony Forming
      Units of TS / mg of biofilm (CFU-TS / mg) were calculated. Results - Total
      Streptococci mean values in CHX (6.77 x 10(6)CFU-TS / mg) were statistically
      lower (p < 0.01) than those in CON (3.82 x 10(7)CFU-TS / mg), but there was no
      statistical difference (p > 0.05) between CHX (168.88 mg) and CON (182.04 mg)
      masses nor statistical correlation (p > 0.05) between biofilm mass and CFU-TS /
      mg in the two groups. CONCLUSION: Chlorhexidine reduces the TS counts in TTBPE,
      but has no effect on biofilm mass.

PMID- 18713151
TI  - Low-energy laser stimulates tooth movement velocity via expression of RANK and
      RANKL.
AB  - OBJECTIVE: Recent studies have demonstrated that low-energy laser irradiation
      stimulates bone formation in vitro and in vivo. However, very little is known
      about the effects of laser irradiation on osteoclastogenesis. The receptor
      activator of the nuclear factor-kB (RANK) / RANK ligand (RANKL) / osteoprotegerin
      (OPG) system is essential and sufficient for osteoclastogenesis. The present
      study was designed to examine the effects of low-energy laser irradiation on
      expressions of RANK, RANKL, and OPG during experimental tooth movement. DESIGN:
      To induce experimental tooth movement in rats, 10 g of orthodontic force was
      applied to the molars. Next, a Ga-Al-As diode laser was used to irradiate the
      area around the moved tooth and the amount of tooth movement was measured for 7
      days. Immunohistochemical staining with RANK, RANKL, and OPG was performed. Real
      time PCR was also performed to elucidate the expression of RANK in irradiated rat
      osteoclast precursor cells in vitro. RESULTS: In the irradiation group, the
      amount of tooth movement was significantly greater than in the non-irradiation
      group by the end of the experimental period. Cells that showed positive
      immunoreactions to the primary antibodies of RANKL and RANK were significantly
      increased in the irradiation group on day 2 and 3, compared with the non
      irradiation group. In contrast, the expression of OPG was not changed. Further,
      RANK expression in osteoclast precursor cells was detected at an early stage (day
      2 and 3) in the irradiation group. CONCLUSION: These findings suggest that low
      energy laser irradiation stimulates the velocity of tooth movement via induction
      of RANK and RANKL.

PMID- 18713152
TI  - Histological analysis of orthodontic root resorption in rats treated with the
      cyclooxygenase-2 (COX-2) inhibitor celecoxib.
AB  - INTRODUCTION: It has been reported that anti-inflammatory drugs used for
      treatment of pain and discomfort related to orthodontic treatment could slow down
      tooth movement. However, the effect of these drugs on orthodontic root resorption
      is not well understood. OBJECTIVES: The aim of this study was to investigate
      whether the COX-2 inhibitor celecoxib offers some protection against
      orthodontically induced root resorption. DESIGN: Male Wistar rats were divided
      into four groups: Groups I and II were treated with saline and celecoxib (10 mg /
      kg), respectively for 3 days. Groups III and IV were treated with saline and
      celecoxib for 14 days. The upper left first molars of all rats were moved
      mesially for 14 days with 50 g of force. An area including the disto-apical
      aspect of the mesial root of the first molar was processed for histological and
      histochemical techniques with tartarate-resistant acid phosphatase (TRAP).
      OUTCOME MEASURE: The degree of root resorption was measured using an image
      analysis system with a grid-sheet superimposed in the root were resorption
      lacunae were counted. The number of TRAP-positive cells on the tooth root surface
      defined as odontoclasts were also evaluated. RESULTS: The results revealed that
      there were no significant differences in the degree of root resorption and in the
      number of odontoclasts on the root between the four groups studied. CONCLUSION:
      The short and long-term celecoxib administration did not suppress the root
      resorption in case of experimental orthodontic force application.

PMID- 18713153
TI  - Automated diagnosis of fetal alcohol syndrome using 3D facial image analysis.
AB  - OBJECTIVES: Use three-dimensional (3D) facial laser scanned images from children
      with fetal alcohol syndrome (FAS) and controls to develop an automated diagnosis
      technique that can reliably and accurately identify individuals prenatally
      exposed to alcohol. METHODS: A detailed dysmorphology evaluation, history of
      prenatal alcohol exposure, and 3D facial laser scans were obtained from 149
      individuals (86 FAS; 63 Control) recruited from two study sites (Cape Town, South
      Africa and Helsinki, Finland). Computer graphics, machine learning, and pattern
      recognition techniques were used to automatically identify a set of facial
      features that best discriminated individuals with FAS from controls in each
      sample. RESULTS: An automated feature detection and analysis technique was
      developed and applied to the two study populations. A unique set of facial
      regions and features were identified for each population that accurately
      discriminated FAS and control faces without any human intervention. CONCLUSION:
      Our results demonstrate that computer algorithms can be used to automatically
      detect facial features that can discriminate FAS and control faces.

PMID- 18713154
TI  - Hemimandibular elongation: treatment and long-term follow-up.
AB  - OBJECTIVE: To study long-term changes in the mandibular asymmetry of patients
      with hemimandibular elongation (HE) treated with two-phase surgical orthodontic
      approach. DESIGN: Descriptive clinical study. SETTING AND SAMPLE POPULATION:
      Private practice setting. Seven (six females) out of 47 diagnosed and treated
      patients for severe mandibular asymmetry were included with the following
      criteria: diagnosis of HE based on clinical, radiological and single photon
      emission computed tomography bone scintigraphic studies, good quality
      orthopantomograms (OPT) available at six time-points, two-phase surgical
      treatment (high condylectomy, HC, and orthognathic surgery, OS) and measurements
      of maximal mouth opening (MMO) available. METHOD: Mandibular ramus height and
      corpus length were measured on OPTs at six time-points. Ratios between the
      affected/non-affected sides were calculated. RESULTS: All patients had
      progression of mandibular asymmetry before any operation, which finding together
      with the scintigraphy resulted to the decision to perform HC. Thereafter ramus
      and corpus asymmetry decreased compared with the initial measurements. After OS,
      stable symmetry of corpuses and alignment of skeletal and dental midlines were
      obtained. MMO reduced on average 50% after HC, regained 20% after OS and
      recovered almost totally at the last follow-up. CONCLUSIONS: High condylectomy to
      stop excessive growth and OS to correct facial asymmetry is considered successful
      and necessary treatment for patients with HE. MMO can well recover after surgical
      traumas. Orthodontists should consider mandibular asymmetry as abnormal and need
      for surgical treatment if asymmetry is progressive and the ratio between
      affected/non-affected sides approaches 10%.

PMID- 18713155
TI  - A three-dimensional look for facial differences between males and females in a
      British-Caucasian sample aged 151/2 years old.
AB  - BACKGROUND: Optical surface scanning accurately records the three-dimension (3D)
      shape of the face non-invasively. Many software programs have been developed to
      process and analyze the 3D data, enabling the clinicians to create average
      templates for groups of subjects to provide a comparison of facial shape.
      OBJECTIVE: Differences in facial morphology of males and females were identified
      using a laser scan imaging technology. SUBJECTS AND METHODS: This study was
      undertaken on 380 British-Caucasian children aged 15 and a half year old,
      recruited from the Avon Longitudinal Study of Parents and Children (ALSPAC). 3D
      facial images were obtained for each individual using two high resolution
      Konica/Minolta laser scanners. The scan quality was assessed and any unsuitable
      scans were excluded from the study. Average facial templates were created for
      males and females, and a registration technique was used to superimpose the
      facial shells of males and females so that facial differences can be quantified.
      RESULTS: Thirty unsuitable scans were excluded from the study. The final sample
      consisted of 350 subjects (166 females, 184 males). Females tend to have more
      prominent eyes and cheeks in relation to males with a maximum difference of 2.4
      mm. Males tend to have more prominent noses and mouths with a maximum difference
      of 2.7 mm. About 31% of the facial shells match exactly (no difference), mainly
      in the forehead and chin regions of the face. CONCLUSIONS: Differences in facial
      morphology can be accurately quantified and visualized using 3D imaging
      technology. This method of facial assessment can be recommended and applied for
      future research studies to assess facial soft tissue changes because of growth or
      healthcare intervention.

PMID- 18713156
TI  - A double-blind, randomized trial of low-dose topiramate vs propranolol in
      migraine prophylaxis.
AB  - OBJECTIVE: To assess the efficacy and safety of low-dose topiramate in migraine
      prophylaxis vs propranolol. PATIENTS AND METHODS: A randomized, double-blind,
      clinical trial including 62 patients with frequent migraine headaches (> or = 3
      attacks per month) was performed for a period of 8 weeks. The patients were
      randomly divided into two treatment groups - treated by topiramate 50 mg/day and
      propranolol 80 mg/day, respectively. The patients were assessed at 0, 4, and 8
      weeks of the study. Results - The topiramate group showed a reduction in the mean
      (+/-SD) of monthly migraine frequency from 6.07 (+/-1.89) to 1.83 (+/-1.39)
      episodes per month, headache intensity from 7.1 (+/-1.45) to 3.67 (+/-2.1) based
      on the Visual Analog Scale, and headache duration from 16.37 (+/-7.26) to 6.23
      (+/-5.22) hours (P < 0.001). In the patients treated with propranolol, the mean
      (+/-SD) of monthly headache frequency declined from 5.83 (+/-1.98) to 2.2 (+/
      1.67) per month, headache intensity lessened from 6.43 (+/-1.6) to 4.13 (+/-1.94)
      and headache duration decreased from 15.10 (+/-6.84) to 7.27 (+/-6.46) h (P <
      0.001). CONCLUSION: This study demonstrated that both low-dose topiramate and
      propranolol could significantly reduce migraine headache frequency, intensity,
      and duration. However, compared with propranolol, low-dose topiramate showed
      better results.

PMID- 18713157
TI  - Role of DNA repair systems in malignant tumor development in the elderly.
AB  - The increased incidence of malignant neoplasms in the elderly is related to the
      accumulation of damaged DNA. We focused on the molecular mechanisms of the DNA
      repair system and examined its relationship to malignant neoplasms in the
      elderly. Hypermethylation of the promoter region of a mismatch repair gene is
      strongly associated with gastric and colorectal carcinomas occurring in the
      elderly. These tumors have characteristic features such as the absence of hMLH1
      expression, microsatellite instability, poorly differentiated histology, low
      incidence of lymph node metastasis and favorable prognosis. On the other hand, we
      analyzed single nucleotide polymorphism (SNP) of the genes in the DNA repair
      system such as hOGG1, p53, XRCC1 and hMLH1 in autopsy cases. Although no
      significant associations were found between the SNP and the number of malignant
      neoplasms, a few SNP were associated with specific tumors. These findings suggest
      that epigenetic changes in the DNA mismatch repair genes play important roles in
      the development of gastric and colorectal carcinomas and that the SNP of DNA
      repair genes have little influence on the occurrence of carcinoma in the elderly.

PMID- 18713158
TI  - Factors enabling home death of the elderly in an institution specializing in home
      medical care: analysis of apprehension of the bereaved family.
AB  - AIM: To determine the factors enabling home death despite caregiver apprehension
      about home medical care. METHODS: This study was an anonymous mailed survey of
      bereaved family members (the caregiver) of patients who died in a home medical
      care setting provided by an institution specializing in home medical care in
      Japan (home death rate, approximately 80%). We analyzed the relationships between
      caregiver apprehension about home medical care, overall satisfaction with home
      medical care and the place of death. RESULTS: Higher caregiver apprehension about
      home medical care and lower overall satisfaction with home medical care were
      significantly associated with dying in a hospital. In addition, the home death
      group with apprehension about home medical care significantly rated higher
      overall satisfaction with home medical care than the hospital death group.
      Meanwhile, there was no difference in the overall satisfaction with home medical
      care between those with or without apprehension about home medical care in the
      home death group. Factors influencing overall satisfaction with home medical care
      in the home death group with apprehension about home medical care were: (i) being
      free from pain or symptoms (partial regression coefficient: 0.83); and (ii)
      fulfilled medical care service system (partial regression coefficient: 0.40).
      CONCLUSION: These results suggest that caregiver satisfaction with home medical
      care is an essential factor to enable home death of the patient despite the
      caregiver apprehension about home medical care.

PMID- 18713159
TI  - Quality of life of the community-based patients with mild cognitive impairment.
AB  - AIM: To determine quality of life (QOL) in patients with mild cognitive
      impairment (MCI) compared to normal subjects and to investigate the impact of
      demographic factors on QOL. METHODS: There were 122 participants aged 50 and
      over, diagnosed with MCI (n = 85) or normal (n = 37) recruited from a community
      based setting in Bangkok. The Thai version of the World Health Organization
      Quality of Life (WHOQOL-BREF-THAI) was used to assess the QOL in the subjects.
      RESULTS: The MCI patients had significantly lower psychological QOL compared to
      normal subjects. The MCI patients with low education had poorer total QOL scores,
      and patients with poor financial status had poorer psychological QOL scores and
      total QOL scores. The MCI patients who lived alone had poorer social relationship
      QOL. There were correlations between the Thai version of Geriatric Depression
      Scale (TGDS) and physical QOL, TGDS and psychological QOL, and TGDS and total QOL
      scores. The depression subscale of the Neuropsychiatric Inventory had negative
      correlation with physical and psychological QOL. CONCLUSION: The MCI patients had
      poorer psychological QOL than normal subjects. Low education, poor financial
      status, living alone and depressive symptoms had an influence on the quality of
      life.

PMID- 18713160
TI  - Description of an orthopedic-geriatric model of care in Australia with 3 years
      data.
AB  - AIM: Orthopedic-geriatric units have been established worldwide to improve the
      care of older patients admitted with fractures. This study describes one type of
      orthopedic-geriatric model which has been implemented in Victoria, Australia,
      named the Orthopedic Aged Care and Rehabilitation Service (OARS) and evaluates
      patient characteristics and outcomes including inpatient mortality. METHODS:
      Eight hundred and thirty-four consecutive admissions under OARS between May 2003
      and May 2006 were analyzed. RESULTS: Mean age was 76.6 years, the majority of
      patients were female (73%) and had come from home (77%). Fractured neck of femur
      represented 51% of all fractures managed by OARS followed by lower limb fractures
      (20%) and upper limb fractures (13%). The majority of patients required inpatient
      rehabilitation (49% of patients overall and 61% specifically for fractured neck
      of femur). Inpatient mortality for all fractures was 2.5% and specifically 3.5%
      for fractured neck of femur. CONCLUSION: The OARS model involves close liaison
      between orthopedic and geriatric teams and promotes a multidisciplinary approach.
      Mortality rate for fractured neck of femur was lower than the state average,
      suggesting that combined orthopedic-geriatric care can improve outcomes.

PMID- 18713161
TI  - White matter lesions as a feature of cognitive impairment, low vitality and other
      symptoms of geriatric syndrome in the elderly.
AB  - AIM: White matter lesions (WML) are common findings on magnetic resonance imaging
      (MRI) in elderly persons. In this study, we analyzed the relation of WML with
      global cognitive function, depression, vitality/volition, and 19 symptoms of
      geriatric syndrome in Japanese elderly patients who attended three university
      geriatric outpatient clinics. METHODS: Two hundred and eighty-six subjects (103
      men and 183 women; mean +/- standard deviation age, 74.5 +/- 7.8 years) were
      included in this study. MRI scans were performed for the diagnosis of WML, and
      the severity of periventricular and deep white matter hyperintensities (PVH and
      DWMH) was rated semiquantitatively. Concurrently, all subjects underwent tests of
      cognitive function, depressive state and vitality, and were examined for 19
      symptoms of geriatric syndrome. RESULTS: The study subjects showed cognitive
      decline, depression and low vitality, all to a mild extent. Univariate linear
      regression analysis showed a negative correlation between the severity of WML and
      cognitive function or vitality. Multiple logistic analysis revealed that the
      severity of WML was a significant determinant of cognitive impairment and low
      vitality, after adjustment for confounding factors such as age, sex and
      concomitant diseases. PVH and/or DWMH score was significantly greater in subjects
      who exhibited 13 out of 19 symptoms of geriatric syndrome. Logistic regression
      analysis indicated that WML were associated with psychological disorders, gait
      disturbance, urinary problems and parkinsonism. CONCLUSION: WML were associated
      with various symptoms of functional decline in older persons. Evaluating WML in
      relation to functional decline would be important for preventing disability in
      elderly people.

PMID- 18713162
TI  - Self-reported assessment of intraoral prostheses among patients attending the
      prosthodontic department in a dental institute in India.
AB  - AIM: This study was conducted to provide a patient assessment of intraoral
      prostheses among subjects who reported to the Department of Prosthodontics,
      Institute of Dental Sciences, Belgaum. METHODS: A nine-item self-designed closed
      ended questionnaire was recorded followed by a clinical examination. Patients who
      reported in a period of 2 months and had at least one prosthesis with a duration
      of usage of at least 1 month were included for the study. Collected data was
      statistically analyzed using the chi(2)-test at a significance level of P < 0.05.
      RESULTS: The questionnaire was answered by 125 patients, 72 completely edentulous
      and 53 partially edentulous, with age ranging 16-84 years (mean age, 54.13 +/- 17
      years). There was a wide variation in the duration of usage of prostheses,
      ranging 3 months to 27 years. Statistically, a highly significant difference was
      found between age and duration of prostheses (chi(2) = 77.29, P < 0.001), between
      the type of prostheses being used with age and opinion with existing prostheses.
      When opinion regarding existing prostheses was compared with sex, age and
      duration of prostheses being used, a statistically significant difference was
      found between opinion with existing prostheses and age, sex and duration of
      prostheses. Of the patients, 49.6% complained of loss of function, 14.4% of loose
      prostheses and 7.2% reported pain with the existing prostheses. CONCLUSION: Loss
      of function was the most common complaint with the existing prostheses among
      complete denture wearers. As the majority of the patients using fixed prostheses
      had no complaint with the prostheses, attention should be paid to preservation of
      natural teeth.

PMID- 18713163
TI  - Cardiac sympathovagal modulation evaluated by short-term heart interval
      variability is subtly impaired in Alzheimer's disease.
AB  - AIM: Alzheimer's disease affects several nervous structures involved with the
      autonomic nervous system. Therefore, the still scarce evaluation of the cardiac
      autonomic function in this disease is of great functional, clinical, prognostic
      and therapeutic relevance. METHODS: Time- and frequency-domain variability of 5
      min R-R interval series in supine and standing positions was comparatively
      evaluated in 22 Alzheimer's disease subjects, aged 60-87 years (mean +/- standard
      error of the mean, 79.6 +/- 1.4) with variable cognitive impairment, and 24
      healthy individuals, aged 60-91 years (68.6 +/- 1.6). The Student's t-test was
      used to compare the variability indices between the groups and logistic
      regression excluded the effects on these indices in the Alzheimer's group of
      confounding variables different from the control group (age, physical activity
      and caffeinated intake), at a significance level of P </= 0.05. RESULTS: No
      difference was observed between the groups (P = 0.12-0.72) for each time-domain
      mean indices and for the frequency-domain indices of overall and absolute
      sympathetic modulation in both positions (P = 0.21-0.78). Absolute
      parasympathetic modulation showed borderline decrease in supine position (P =
      0.07) and was reduced in the standing (P = 0.05). The sympathovagal balance was
      altered (P = 0.05) toward relative parasympathetic borderline depression (P =
      0.07) and sympathetic exacerbation (P = 0.04) only in the supine posture.
      CONCLUSION: Data indicate that Alzheimer's disease subjects with mild-to-severe
      cognitive dysfunction showed subtle, absolute and relative parasympathetic
      depression and relative sympathetic exacerbation, which may even so contribute to
      distinctive functional and cognitive disturbances.

PMID- 18713164
TI  - Diagnosis and treatment of lower urinary tract symptoms in the elderly by general
      practitioners.
AB  - AIM: We investigated the diagnosis and treatment of lower urinary tract symptoms
      (LUTS) by general practitioners (GPs) according to the Practical Manual for LUTS
      Evaluation and Treatment in the Elderly For GPs. METHODS: Using the manual, 14
      GPs determined LUTS severity using the International Prostate Symptom Score,
      Quality of Life Index, post-void residual urine volume and the International
      Consultation on Incontinence Questionnaire-Short Form, then evaluated utilization
      of the frequency volume charts and other examinations to treat LUTS and assessed
      treatment effectiveness. RESULTS: This study included 52 men (aged 71 +/- 9
      years) and 37 women (73 +/- 9). Voiding symptoms were more frequent in men but
      storage symptoms occurred similarly in both sexes. The overall severities of LUTS
      were similar between sexes. Of 36 men and 27 women who were treated, water
      restriction for polyuria and nocturnal polyuria was recommended for 17 men and 14
      women, bladder training for six women, and pelvic floor exercise for three men
      and 16 women as behavioral therapy. Of 27 men and 25 women whose treatment
      effectiveness was assessed by GPs, effectiveness was judged as "fairly good" or
      greater in 20 men (74%) and 23 women (92%). Eleven men (40%) and 20 women (80%)
      were satisfied with their treatment. CONCLUSION: It is suggested that GPs can
      provide high-quality LUTS practice when they follow the manual and use the
      recommended tools for evaluation and monitoring.

PMID- 18713165
TI  - Successful treatment of spondylolisthesis with medicinal herbs.
AB  - It has been reported that some herbal medicines may be effective for acute
      episodes of chronic nonspecific lower back pain. Spondylolisthesis is one of the
      causes of lower back or neck pain. To our knowledge, successful treatment of
      symptomatic spondylolisthesis with medicinal herbs has not been previously
      reported in the published work. A 63-year-old female had suffered from back pain
      for 4 years. Radiographs revealed spondylolisthesis at the L3 level. In another
      case, an 82-year-old female suffered from neck pain. X-ray examinations revealed
      cervical spondylolisthesis at the C4 level. Several herbs were administered to
      these patients with symptomatic spondylolisthesis according to the guidelines for
      herbal medicine. Significant improvements in pain were obtained within 4 weeks in
      both patients. The pain completely disappeared after 20 weeks (case 1) and 6
      weeks (case 2) of treatment. Although surgical treatment is often performed for
      symptomatic spondylolisthesis, the findings of the present cases imply the
      therapeutic potential of herbal medicine in selected patients.

PMID- 18713166
TI  - Multidisciplinary approach to "accidental" falls in the elderly: a case report.
AB  - Falls in the elderly are commonly and often wrongly identified as "accidental".
      We report a case of an elderly woman admitted to first aid for a trauma due to an
      accidental fall. Geriatric multidisciplinary evaluation revealed mild cognitive
      impairment associated with depressive symptoms; both findings made the anamnesis
      uncertain. Syncope algorithm was applied and "tachy-brady form of sick sinus
      syndrome" was diagnosed. Differential diagnosis between "accidental" and
      "apparently accidental" falls in elderly patients is very difficult but a
      multidisciplinary geriatric evaluation can clarify the correct diagnosis.

PMID- 18713167
TI  - Ischemic nephropathy in an elderly patient.
AB  - Congestive heart failure often occurs in patients with bilateral renal artery
      stenosis. Recently, Jacobson and Breyer, and Jacobson introduced the term
      "ischemic nephropathy", which implies critical bilateral involvement or global
      ischemia. Ischemic nephropathy is not only a cause of hypertension but also an
      important cause of end-stage renal disease. However, the aging kidney often show
      that the renal artery does not demonstrate stenosis of the main trunks, but
      stenosis of an atherosclerotic branch. We present a case of multiple
      atherosclerotic peripheral renal arteries, which might have caused ischemic
      nephropathy in an elderly hypertensive patient with advanced atherosclerosis.

PMID- 18713168
TI  - Lavender aroma therapy for behavioral and psychological symptoms in dementia
      patients.

PMID- 18713169
TI  - Ethnic aged discrimination and disparities in health and social care: a question
      of social justice.
AB  - Older overseas-born Australians of diverse cultural and language backgrounds
      experience significant disparities in their health and social care needs and
      support systems. Despite being identified as a 'special needs' group, the ethnic
      aged in Australia are generally underserved by local health and social care
      services, experience unequal burdens of disease and encounter cultural and
      language barriers to accessing appropriate health and social care compared to the
      average Australian-born population. While a range of causes have been suggested
      to explain these disparities, rarely has the possibility of cultural racism been
      considered. In this article, it is suggested that cultural racism be named as a
      possible cause of ethnic aged disparities and disadvantage in health and social
      care. It is further suggested that unless cultural racism is named as a
      structural mechanism by which ethnic aged disparities in health and social care
      have been created and maintained, redressing them will remain difficult.

PMID- 18713170
TI  - The acute-aged care interface: exploring the dynamics of 'bed blocking'.
AB  - OBJECTIVE: To understand the dynamics underlying 'bed-blocking' in Australian
      public hospitals that is frequently blamed on older patients. METHODS: Analysis
      of primary and secondary data of utilisation patterns of hospital and aged care
      services by older Australians. RESULTS: A model of the dynamics at the acute-aged
      care interface was developed, in which the pathway into permanent high-care
      Residential Aged Care (RAC) is conceptualised as competing queues for available
      places by applicants from the hospital, the community and from within RAC
      facilities. The hospital effectively becomes a safety net to accommodate people
      with high-care needs who cannot be admitted into RAC in a timely manner.
      CONCLUSION: The model provides a useful tool to explore some of the issues that
      give rise to access-block within the public hospital system. Access-block cannot
      be understood by viewing the hospital system in isolation from other sectors that
      support the health and well-being of older Australians.

PMID- 18713171
TI  - Individual differences in South Australian general practitioners' knowledge,
      procedures and opinions of the assessment of older drivers.
AB  - OBJECTIVE: Investigate individual differences in general practitioners' (GP)
      knowledge, procedures and opinions of older driver assessments. METHODS: Ninety
      nine South Australian GPs completed a survey on their knowledge, procedures and
      opinions concerning fitness to drive assessments in older people. RESULTS: Most
      GPs were well informed about older driver legislation and used appropriate
      medical assessments when considering fitness to drive. However, there was much
      less consistency in the assessment of relevant cognitive abilities. Most GPs
      believed that there was a need for more transport and support services for older
      drivers when they ceased driving. Demographic and qualitative information helped
      explain some differences in both GPs' practice and opinions concerning the
      assessment of older drivers. CONCLUSIONS: Measures should ensure that GPs have
      accurate knowledge of legislation concerning older drivers; appropriate tests of
      driving-related cognitive abilities are available; and transport and support
      options for those older individuals who are no longer fit to drive are
      considered.

PMID- 18713172
TI  - Determinants of work among older adults in urban China.
AB  - OBJECTIVE: We examined the role of personal, family and institutional factors on
      the work status of older adults in urban China. METHOD: The analysis was based on
      data from a large population survey (N = 7381) of community-dwelling urban
      Chinese aged 60 years and older. Multivariate logistic regression was used to
      model work status. RESULTS: Demographic variables such as gender, ethnicity, age
      and self-perceived health status were identified as important determinants of
      work status. Having material assets, savings, a public pension and health
      insurance were all negatively correlated with remaining in the workforce, whereas
      earning a high income was positively correlated. CONCLUSIONS: Our findings have
      implications regarding the impact of health policy and pension reform on
      employment retention. While economic growth may create an incentive for some to
      continue working, the lack of widespread public and private old-age support may
      force others to remain in the workforce out of economic necessity.

PMID- 18713173
TI  - Antipsychotic use in the elderly: what doctors say they do, and what they do.
AB  - OBJECTIVE: To review psychiatrists' attitudes and actual practice on the use of
      typical and atypical antipsychotics in the elderly. METHODS: Audit data were
      collected from 18-old-age psychiatry units across Australia. The attitudes of old
      age psychiatrists and their perceptions of the efficacy, tolerability and
      clinical usefulness of antipsychotics were examined. RESULTS: The medications
      used for 321 patients were audited, and the attitudes of the 57 prescribing
      doctors were assessed. All available atypicals were prescribed and reported as
      more efficacious and clinically useful than typicals. Adverse events perceived by
      doctors as an obstacle to prescribing were more frequent than reported adverse
      event rates in product information. All diagnostic groups improved. Off-label use
      comprised almost 22% in this sample. CONCLUSIONS: Adverse events are impediments
      to prescribing, more so with typical than atypical antipsychotics. All available
      atypicals were used and appeared effective in this elderly population.

PMID- 18713174
TI  - Improving communicable disease outbreak preparedness in residential aged care
      facilities using an interventional interview strategy.
AB  - OBJECTIVE: To improve the capacity of residential aged care facilities (RACFs) to
      respond to communicable disease outbreaks. METHODS: Three computer-assisted
      telephone interviews were conducted with RACFs. The first survey gathered
      baseline information. Outbreak prevention resources were then offered to address
      identified weaknesses. Subsequent surveys enabled the facilities' progress to be
      monitored. Before the third survey, RACFs were sent a personalized scorecard
      documenting their standing against 19 readiness criteria. RESULTS: RACFs
      reporting an outbreak management plan increased from 58 to 98%, and facilities
      reporting 16 or more of the 19 readiness criteria rose from 24 to 43% (P <
      0.0006) at the second interview and 73% at the third interview (P < 0.0001).
      CONCLUSIONS: The strategy resulted in a significant improvement in reported
      outbreak readiness.

PMID- 18713175
TI  - Clinical practice guidelines for the management of delirium in older people in
      Australia.
AB  - Delirium is a common and serious condition which is often overlooked or
      misdiagnosed in older people. In 2006, the first set of national clinical
      practice guidelines for the management of delirium in older people were
      developed. This paper provides an abbreviated version of the guideline document
      which includes recommendations for the detection of delirium (diagnosis and
      screening), assessment and prediction of risk factors for delirium, prevention of
      delirium and interventions to manage people with delirium. The guidelines reflect
      the available evidence base and highlight the limited high level research in
      delirium care, particularly in the areas of symptom management and screening for
      delirium.

PMID- 18713176
TI  - Dementia severity and on-road assessment: briefly revisited.
AB  - OBJECTIVE: Drivers with dementia should cease driving if unsafe. This report aims
      to add to the evidence concerning use of global dementia severity as an indicator
      of driving performance. METHOD: One hundred and fifteen drivers were assessed via
      standardised on-road assessment. Descriptive and comparative statistics analysed
      age and global dementia severity of the drivers against the on-road assessment
      outcome. RESULTS: On-road assessment outcomes conformed to previous clinical
      guidelines in outer limits of dementia severity. Drivers with negligible dementia
      passed the assessment, those with moderate dementia failed. The pass or fail
      outcomes for drivers with very mild and mild dementia were equivocal. CONCLUSION:
      This study supports previous recommendations of cessation or continued driving
      for those in outer margins of dementia severity. Use of severity levels for
      driving recommendations, in the absence of on-road assessment, risks either
      continued unsafe driving or premature cessation for individual drivers with very
      mild or mild dementia.

PMID- 18713177
TI  - Public provision of four-wheeled walkers: contingent valuation study of economic
      benefit.
AB  - OBJECTIVE: To quantify the economic value of publicly provided four-wheeled
      walkers as judged by recipients in Queensland, Australia. METHOD: Contingent
      valuation study using willingness-to-pay approach. A sample of 49 Australian
      older adults who received a publicly funded four-wheeled walker in the past 3
      months completed the survey via telephone. A discrete choice bidding response
      format with a randomly selected starting bid was employed to glean valuations.
      RESULTS: This approach yielded only one non-response, and one zero dollar
      response. The mean (standard deviation) valuation provided was $ A 290 ($ A 167),
      which was $ A 84 in excess of the price paid by the public provider agency to
      purchase the equipment. Starting bid was significantly associated with values
      provided. CONCLUSION: The current public provision program of four-wheeled
      walkers is likely to generate net societal benefit. These findings coupled with
      arguments based on equity build a moderate case for the continuation of this
      program.

PMID- 18713182
TI  - Single pathogenesis of geriatric syndrome.

PMID- 18713183
TI  - Optimal treatment of hypertension in the elderly: a Korean perspective.
AB  - With the progression of the aging population, common diseases of the elderly have
      become the center of attention in most developed countries. Hypertension is one
      of the most common morbid conditions in the elderly and has a great impact on
      their health status because it is the main risk factor of cardiovascular and
      cerebrovascular diseases. However, a considerable amount of uncertainty remains
      regarding hypertension in the elderly, such as the benefits of hypertension
      control in oldest-old populations, the optimal level of blood pressure control,
      and the efficacy of antihypertensive drugs for the prevention of cognitive
      dysfunction. While there are many controversial issues concerning the optimal
      management of hypertension in the elderly, the number of elderly hypertensive
      patients that require treatment is expected to increase due to the aging
      population. As a result, knowledge regarding the mechanisms of hypertension in
      the elderly and specific consideration in managing hypertensive elderly patients
      are needed to improve the clinical outcome. Furthermore, new therapeutic
      interventions that are aimed at attenuating age-related vascular changes should
      be investigated, because hypertension in the elderly, especially isolated
      systolic hypertension has specific characteristics of increased arterial
      stiffness in most cases.

PMID- 18713184
TI  - Factors associated with carotid atherosclerosis in community-dwelling oldest
      elderly aged over 80 years.
AB  - BACKGROUND: Hypertension, hyperlipidemia, impaired glucose tolerance and smoking
      have been known to be risk factors for atherosclerosis. Recently, it was shown
      that hyperhomocysteinemia is also a risk factor for cerebral vascular disease and
      atherosclerosis. However, it is unknown if these are also risk factors in the
      oldest elderly population aged 80 years or older. We carried out a cross
      sectional analysis to determine the associated factors with carotid
      atherosclerosis in the oldest elderly living in the community. METHODS: Subjects
      consisted of 136 oldest elderly aged 80 years or older living in the community.
      Blood pressure, orthostatic change of blood pressure, blood chemical parameters,
      height and bodyweight, lifestyle and medical history were examined. The thickness
      was measured of the total carotid artery intima-media complex (IMT) by carotid
      artery ultrasonography and used the maximum thickness (max IMT) for analysis.
      RESULTS: The factors that correlated with max IMT were age and low gamma-glutamyl
      transpeptidase in males, and serum homocysteine levels in females. The subjects
      were divided into two groups: those with a max IMT of less than 1.0 mm and those
      with that of 1.0 mm or more. Factors associated with max IMT were age and
      abstinence from alcohol in males, and orthostatic blood pressure change in
      females. Factors significantly associated with higher carotid artery IMT were
      aging in males and orthostatic blood pressure change in females. CONCLUSION: The
      factors associated with carotid artery IMT as an indicator of carotid
      atherosclerosis in community-dwelling oldest elderly aged 80 years or older were
      sex, aging, orthostatic blood pressure change and no alcohol intake. There were
      differences in risk factors for carotid atherosclerosis between the male and
      female population.

PMID- 18713185
TI  - Long-term outcome after placement of a percutaneous endoscopic gastrostomy tube.
AB  - AIM: To evaluate long-term survival and prognostic factors in patients who have
      undergone placement of a percutaneous endoscopic gastrostomy tube. METHODS: A
      retrospective analysis of all patients without malignancy who underwent
      percutaneous endoscopic gastrostomy at Hanyu General Hospital during the period
      January 2001-December 2005. RESULTS: A total of 198 patients (100 men, 98 women)
      were assessed. Median age was 78 years (range, 25-97 years). The primary
      diagnosis was a cerebrovascular disorder in 149 (75.3%) of the patients. Prior to
      placement, 120 (60.6%) had suffered pneumonia. Survival was 87.4% at 1 month,
      67.8% at 3 months, 52.6% at 6 months, 38.1% at 1 year, 27.8% at 2 years and 22.3%
      at 3 years. Pneumonia was the most common cause of death during the follow-up
      period (91 of 140 patients, 65.0%). Cox's proportional hazards model showed
      independent predictors of mortality to be a low serum albumin concentration
      (<or=2.9 g/dL) and history of pneumonia before the procedure. CONCLUSIONS:
      Mortality of patients who underwent percutaneous endoscopic gastrostomy appears
      to be high. In particular, the long-term prognosis was poor for patients with
      hypoalbuminemia, and this procedure is probably not preferred for patients with
      recurrent aspiration pneumonia.

PMID- 18713186
TI  - Comprehensive assessment of nutritional status and associated factors in the
      healthy, community-dwelling elderly.
AB  - BACKGROUND: Malnutrition among the elderly has become a serious problem as their
      population increases in Japan. To approach the risk of malnutrition in the
      healthy, community-dwelling elderly is important for early prevention of
      malnutrition. The nutritional status and mutable associated factors with poor
      nutritional status specific to the healthy elderly were examined comprehensively.
      METHODS: One hundred and thirty healthy elderly people from a senior college in
      Tokyo, Japan were eligible for this study. Nutritional status was evaluated by
      Mini-Nutritional Assessment (MNA). The demographic status and potential
      correlates with poor nutritional status, including the physical factors
      (mobility, cognitive impairment and oral status) and the psychosocial factors
      (depression, self-efficacy, attitudes toward health, instrumental activities of
      daily living, public health service knowledge, and difficulty and dissatisfaction
      with meal preparation) were investigated. The multiple linear regression analysis
      using a stepwise procedure adjusted for demographic status was performed to
      detect independent associated factors. RESULTS: There were 16 participants
      (12.6%) at risk of malnutrition. The independent associated factors with lower
      MNA scores were depression (beta = -0.27, P = 0.005), lower self-efficacy (beta =
      0.25, P = 0.009), lower attitudes toward health scores (beta = 0.21, P = 0.02)
      and difficulty with meal preparation (beta = -0.18, P = 0.03). CONCLUSION: The
      prevalence of the healthy elderly at the initial risk of malnutrition was
      relatively high and should not be overlooked. The comprehensive geriatric
      screening and intervention including mental health, health management and life
      situation will be important for the healthy, community-dwelling elderly.

PMID- 18713187
TI  - Relationships between working status and health or health-care utilization among
      Japanese elderly.
AB  - BACKGROUND: As we have previously proposed redefining elderly from "65 years and
      over" to "75 and over" in Japan, many elderly Japanese now keep working beyond
      the traditional retirement age, around 60-65 years of age, in this rapidly aging
      society. It is important to assess the influence of working status on health and
      health-care utilization among elderly Japanese. METHODS: We evaluated a random
      sample of community-dwelling Japanese elderly, aged 55-74 years. Data were
      collected using a health diary strategy. For health-related quality of life
      (HRQOL), we used SF-8 with a physical component summary (PCS8) and a mental
      component summary (MCS8). Health-care utilization included visiting physicians as
      well as using dietary and physical complementary and alternative medicine (CAM).
      RESULTS: Among 679 participants aged 65-74 years (40.6% men), there were 254
      (37.4%) working and 425 (62.6%) non-working. PCS8 and MCS8 were not significantly
      different between the working status groups. There were no differences in the
      rate for visiting physicians and using dietary and physical CAM between the
      working and non-working, except for those aged 70-74 years, who exhibited a
      higher rate for visiting a physician among the non-working. A higher annual
      personal income showed a significant association with better PCS8 (P = 0.031) and
      a trend towards better MCS8 (P = 0.055). The older participants were more likely
      to report better MCS8 than the young regardless of working status (P = 0.007).
      CONCLUSION: Working status itself does not appear to associate with health and
      health-care utilization among elderly Japanese. Working with a higher income may
      potentially improve HRQOL.

PMID- 18713188
TI  - Influence of diabetes mellitus on caregiver burden in home care: a report based
      on the Nagoya Longitudinal Study of the Frail Elderly (NLS-FE).
AB  - BACKGROUND: Because little attention has so far been paid to the impact of
      diabetes mellitus (DM) on caregiver burden in community settings, we sought to
      confirm the influence of DM on perceived caregiver burden among caregivers
      providing care to a home elderly person using data from the Nagoya Longitudinal
      Study of the Frail Elderly (NLS-FE). METHODS: The NLS-FE is a large prospective
      study of 1875 community-dwelling elderly. A total of 1592 pairs of dependents and
      caregivers were included in the analysis. The data we used in this study included
      the Japanese version of the Zarit Caregiver Burden Interview (J-ZBI),
      characteristics of caregivers and dependents, and caregiving situation. The pairs
      were sorted into one control and three DM groups: (i) no DM; (ii) DM taking no
      medications; (iii) DM taking oral medication only; and (iv) DM taking insulin.
      The differences in dependent and caregiver characteristics among the groups were
      assessed. RESULTS: Two hundred and twenty-eight dependents from the NLS-FE study
      had DM. Of these, 25% took no medication to treat it, 55% took oral medications
      only, and 20% used insulin. No statistical differences were found in age, gender
      or kinship among caregivers. No differences were found among the DM categories in
      levels of caregiver burden according to the J-ZBI, before and after adjusting for
      these baseline variables. CONCLUSIONS: Among the community-dwelling frail
      elderly, DM is not an independent predictor of caregiver burden.

PMID- 18713189
TI  - Measuring disability in older adults: the International Classification System of
      Functioning, Disability and Health (ICF) framework.
AB  - BACKGROUND: Despite the importance of disability to geriatric medicine, no large
      scale study has validated the activity and participation domains of the
      International Classification System of Functioning, Disability, and Health (ICF)
      in older adults. The current project was designed to conduct such as analysis,
      and then to examine the psychometric properties of a measure that is based on
      this conceptual structure. METHODS: This was an archival analysis of older adults
      (n = 1388) who had participated in studies within our Claude D Pepper Older
      Americans Independence Center. Assessments included demographics and chronic
      disease status, a 23-item Pepper Assessment Tool for Disability (PAT-D) and 6-min
      walk performance. RESULTS: Analysis of the PAT-D produced a three-factor
      structure that was consistent across several datasets: activities of daily living
      disability, mobility disability and instrumental activities of daily living
      disability. The first two factors are activities in the ICF framework, whereas
      the final factor falls into the participation domain. All factors had acceptable
      internal consistency reliability (>0.70) and test-retest (>0.70) reliability
      coefficients. Fast walkers self-reported better function on the PAT-D scales than
      slow walkers: effect sizes ranged from moderate to large (0.41-0.95); individuals
      with cardiovascular disease had poorer scores on all scales than those free of
      cardiovascular disease. In an 18-month randomized clinical trial, individuals who
      received a lifestyle intervention for weight loss had greater improvements in
      their mobility disability scores than those in a control condition. CONCLUSION:
      The ICF is a useful model for conceptualizing disability in aging research, and
      the PAT-D has acceptable psychometric properties as a measure for use in clinical
      research.

PMID- 18713190
TI  - Spontaneous bilateral fracture of patella.
AB  - Bilateral patellae fractures represent a rare entity, accounting for
      approximately 2.9% of all lesions interesting in this anatomical district. In
      most cases found in the published work, they are described as stress fractures or
      as complications of chronic diseases such as osteoporosis, renal failure and
      secondary hyperparathyroidism. Although many pathogenetic mechanisms have been
      supposed, none have been proved for certain. Insufficiency fractures of the
      patellae are rare events and no data has been published on their incidence. We
      present a case of bilateral fracture of the patellae due to an indirect trauma
      occurring in an 85-year-old patient affected by Parkinson's disease, osteoporosis
      and diffuse degenerative osteoarthritis. X-ray of the knees (anteroposterior and
      lateral) and magnetic resonance imaging evaluation confirmed the fractures. The
      patient was treated conservatively. She had a good result, returning to her
      previous autonomous ambulation. This case is unusual because there was no direct
      trauma to the knees because of bilaterality, but confirmed previous observations
      about insufficiency fractures of patellae in the presence of comorbidity.
      Insufficiency fractures of patellae can be an insidious condition in elderly
      people. Prepatellar pain, a common symptom in the relapse phase of degenerative
      arthritis of the knee, should not be underestimated, particularly in patients
      with diseases influencing metabolism of bone and with an elevated risk of fall. A
      periodical clinical and instrumental follow up should be done in these patient.
      Moreover, we underline the necessity of a multidisciplinary approach.

PMID- 18713191
TI  - Azelastine hydrochloride on behavioral and psychological symptoms and activities
      of daily living in dementia patients.

PMID- 18713192
TI  - Salt taste perception and salt intake in older people.

PMID- 18713193
TI  - Healthy ageing in rural Australia: issues and challenges.
AB  - Approximately 36% of the rural Australian population is 65 years and older. In
      fact, many rural and remote communities have higher proportions of older people
      than metropolitan centres. The rate of growth, patterns of migration, higher
      levels of health risk factors and of social and economic disadvantage all impact
      on rural healthy ageing. Older people in rural communities have become
      marginalized by longstanding misconceptions about rural life and urban-centric
      policies, much of which goes unchallenged because of a paucity of research in key
      areas and a lack of intrarural research. Understanding the complexities of rural
      healthy ageing is challenging, and more research is required to develop a
      stronger empirical base. The aim of this review is to critique the literature
      related to rural ageing in Australia to identify the issues and challenges for
      rural healthy ageing and implications for policy and practice.

PMID- 18713194
TI  - The challenges of clinical trials in the exclusion zone: the case of the frail
      elderly.
AB  - Frail older people have been systematically excluded from randomised controlled
      trials (RCT). We aim to recruit older, frail hospitalised patients in an RCT and
      evaluate the frailty index (FI) as a measure to describe the types of people
      included in the study. We recruited 315 hospitalised patients aged 65 years; age
      ranged from 60 to 102 years. Baseline assessment scores ranged as follow: Mini
      Mental Status Examination from 7 to 30, Barthel index from 5 to 100 and FI from 2
      to 24. Total deaths were 20 (6%). We demonstrated that it is feasible to recruit
      frail older people into RCTs. The FI does not show any 'floor' or 'ceiling'
      effects. We can measure frailty in an RCT cohort, and we believe that clinical
      trials should include more frail older people and that the use of an FI can
      facilitate such trials and generate reliable data to guide future medical
      practice in a rapidly ageing society.

PMID- 18713195
TI  - Issues of active ageing: perceptions of older people with lifelong intellectual
      disability.
AB  - OBJECTIVE(S): The study aimed to investigate the lived experiences of older
      people with lifelong intellectual disability and to explore the meaning of active
      ageing for this group. METHODS: Data were collected using semistructured
      interviews with 16 service users (people with lifelong intellectual disability
      aged 50+ years); 16 service providers and 16 key informal network members from
      regional/rural and urban areas in Queensland and Victoria. RESULTS: Themes
      identified: being empowered, being actively involved, having a sense of security,
      maintaining skills and learning, having congenial living arrangements, having
      optimal health and fitness, being safe and feeling safe and having satisfying
      relationships and support. CONCLUSIONS: Service users wanted to 'keep on keeping
      on' in areas of life that gave them pleasure rather than discontinuing them
      because of age. They wanted more control over issues affecting their lives and to
      be given meaningful roles. Mental stimulation, companionship, reliable support
      and safety were valued by this group.

PMID- 18713196
TI  - Perceptions of personal safety among older Australians.
AB  - INTRODUCTION: There is public perception, partly attributable to the media, that
      older people are disproportionately the victims of crime and are greatly
      concerned for their personal safety. OBJECTIVES: To identify at a population
      level older people's perceptions of their personal safety in their home and
      separately in their neighbourhood, and the predictors of feeling safe in each
      setting. METHODS: Logistic regression analysis of responses from randomly
      selected older Australians (65+ years) living independently in the community (n=
      8881) to a cross-sectional telephone general health survey. RESULTS: The vast
      majority of respondents, although higher in men, reported feeling safe in their
      home (96%) and neighbourhood (92%) 'all' or 'most' of the time. Feeling safe did
      not decline with age. Significant predictors of feeling safe 'all' the time were
      identified and some gender differences were noted. CONCLUSIONS: The perception
      that older people are greatly concerned with their personal safety is not
      supported by these findings.

PMID- 18713197
TI  - Ageing, social capital and the Internet: findings from an exploratory study of
      Australian 'silver surfers'.
AB  - OBJECTIVE: To document the sociodemographic characteristics and online use
      patterns of older Australian Internet users as part of an exploratory study of
      the relationship between Internet communication and access to social capital in
      later life. METHODS: A purposive sample of 154 Internet users aged 55 years or
      older and not employed full time completed an electronic survey about their
      social characteristics and patterns of Internet use. A subsample of 30
      participated in follow-up in-depth interviews. RESULTS: The majority of
      participants comprised married, home-owning, English-speaking women and men in
      good health. They made extensive use of the communication and information
      functions of the Internet to supplement and enhance their connections with
      friends and family and their engagement with wider social networks. CONCLUSION:
      Policy development should be informed by better understanding of the potential
      and limitations of the Internet as a tool for generating and sustaining social
      capital in old age.

PMID- 18713198
TI  - Influence of different health-care systems on health of older adults: a
      comparison of Hong Kong, Beijing urban and rural cohorts aged 70 years and older.
AB  - OBJECTIVE: To explore the hypothesis that better health status of elderly
      populations is primarily determined by the provision of freely accessible health
      service at low or no cost to the user and a social welfare system. METHOD:
      Information was collected by questionnaire from surveys of three cohorts of
      elderly (70 years and older) Chinese. Data from two health-care systems were
      compared: the low-cost or free government-subsidized system in Hong Kong, and the
      market-orientated user-pays system in urban (Beijing), and rural China. RESULTS:
      The Beijing rural cohort had the best health profile, whereas the Hong Kong
      cohort had the worst, despite the better lifestyle practices in the Hong Kong and
      Beijing urban cohorts compared with the Beijing rural cohort, and higher
      socioeconomic status in the Beijing urban and Hong Kong cohorts. However, the
      Beijing rural cohort had the highest prevalence of functional limitations.
      CONCLUSION: While health-care systems may affect life expectancy at birth,
      psychosocial, lifestyle and socioeconomic factors influence subsequent health
      status of elderly people in a complex manner.

PMID- 18713199
TI  - Dying with dementia: the views of family caregivers about quality of life.
AB  - OBJECTIVE: To document the views of family caregivers of persons with dementia
      about quality of life for their relative during the late and terminal stages of
      the disease, as part of an exploratory study of best quality care and support.
      METHODS: Fifteen former caregivers (five wives, five husbands, two sons, three
      daughters) participated in in-depth semistructured interviews. RESULTS:
      Participants identified three main sets of indicators of quality of life: the
      physical body, the physical and social environment and treatment with respect and
      dignity. The constructs 'quality of life' and 'quality of care' tended to be
      conflated in the experience of caregivers. An important role for caregivers was
      to interpret and represent the subjective experience of the person with dementia.
      CONCLUSION: Quality of life needs to be understood from multiple perspectives.
      Caregivers' views are a central part of this understanding and should be used to
      inform future research and service development.

PMID- 18713200
TI  - The aged care pain chart: an innovative approach to assessing, managing and
      documenting pain in older people.
AB  - This article presents the development and initial testing of a comprehensive pain
      chart for the assessment, management and documentation of pain in older people in
      subacute and residential aged care. The pain chart was developed from existing
      assessment scales and pain indicators, and is targeting needs of older people in
      residential care and geriatric hospital settings with high prevalence of
      cognitive impairments. The chart is based on self-report of pain but allows for
      observation of pain-related behaviours for those unable to report pain. The chart
      consists of one evaluative and one documentation dimension, and was evaluated by
      a group of clinicians in geriatric hospital care (n = 15) and residential aged
      care (n = 6). The chart was found to be content valid, informative and easy to
      use, facilitating clinical assessments and monitoring, and assisting visual
      readings of patients' temporal pain trends.

PMID- 18713201
TI  - What are the first quality reports from the Transition Care Program in Australia
      telling us?
AB  - Transition Care is a new program in Australia, jointly funded by the Commonwealth
      and State/Territory Governments. Implementation is undertaken by state health
      departments, in some cases through aged care organisations, against a set of key
      requirements. This paper examines reports from providers to reveal enablers and
      barriers to compliance with the requirements and to highlight emerging patterns
      of practice. The first 23 self-reports were content analysed. Person-centred and
      goal-orientated care was evidenced. General practitioner, pharmacist and
      geriatrician involvement in care planning and review was low. While service
      agreements between Transition Care services, referring hospitals and community
      providers improved the efficiency of information transfer and discharge
      arrangements, these were rare, hindering entry and discharge from the program.
      Transition Care offers older people a flexible model of care. While the
      flexibility of the model is a strength, service providers are struggling to
      achieve integration with existing services.

PMID- 18713202
TI  - Personal emergency alarms: what impact do they have on older people's lives?
AB  - OBJECTIVES: To determine if, how often and in what types of situations older
      people use personal alarms and to explore the impact of personal alarm technology
      on older people's lives. METHODS: This study was retrospective and involved a
      mail-out survey to 2610 users of the Silver Chain Care Link Personal Alarm
      Service. RESULTS: Clients wear their alarm consistently around their home and in
      the garden; however, use is low in the shower/bath and in bed at night. Clients
      reported positive impacts in terms of: gaining faster assistance in an emergency,
      extending the time they are able to remain living at home, increasing their sense
      of security, reducing anxiety about falling and increasing confidence in
      performing everyday activities. CONCLUSIONS: Personal alarms have many positive
      impacts on the lives of older people.

PMID- 18713207
TI  - Australasian Journal on Ageing. Editorial.

PMID- 18713208
TI  - Pharmaco-epistemology for the prescribing geriatrician.
AB  - Clinicians are becoming more reliant on their interpretation of clinical trial
      information to guide prescribing rather than their clinical skills. Thus to
      improve prescribing, it is increasingly important for clinicians to have an
      appreciation of epistemology (the science of knowledge and its interpretation)
      and the broader social context of knowledge. The insights of epistemologists can
      be useful in understanding the different ways in which clinical trials data are
      interpreted.

PMID- 18713209
TI  - Current issues on ageing in Japan: a comparison with Australia.
AB  - Japan's demography has changed dramatically, and with it, Japanese society and
      the circumstances of older people. These changes include shifts in family roles
      and functions, employment and social relations. Traditionally, families provided
      financial, physical and psychological support to their parents in the same
      household. While the proportion of older Japanese who live with adult children is
      still high in comparison to the rate in Western developed countries, patterns of
      care in Japan are gradually shifting towards the Western model. Public pensions
      supply financial support and the Long-Term Care Insurance System (LCIS) provides
      substantial physical care for frail older people. This paper focuses on current
      issues for older people in Japan, and provides a brief comparison with the
      situation in Australia. Japan's LCIS provides a simpler and more consistent basis
      for funding long-term care than Australia's system. On the other hand,
      Australia's pension system is comparatively robust.

PMID- 18713210
TI  - Is bigger better when it comes to defining target populations for aged care
      programs?
AB  - OBJECTIVES: To compare the Home and Community Care Program (HACC) target
      population defined on the basis of the ABS Survey of Disability, Ageing and
      Carers (SDAC) with 2006 census data on need for assistance. METHODS: The number
      of people with different levels of core activity limitation as defined in the
      SDAC was estimated for the 2006 population aged 65 and older and compared with
      the number reporting a need for assistance in the 2006 census. RESULTS: The two
      target populations differ in size, age and disability levels, but the differences
      are reconciled when components within the total SDAC-defined target population
      are taken into account. DISCUSSION: Assessment of different definitions of target
      populations in terms of validity in identifying program beneficiaries, accuracy
      in measurement and usefulness in monitoring program performance leads to the
      conclusion that the bigger SDAC-defined population is better aligned with the
      goals of the HACC program.

PMID- 18713211
TI  - Correlates of housing affordability stress among older Australians.
AB  - OBJECTIVES: The purpose of this study was to examine the prevalence and
      correlates of housing affordability stress among community-dwelling older
      Australians. METHODS: The 2002 ABS General Social Survey was used to measure the
      prevalence of housing affordability stress. Rare event logistic regression was
      used to measure the potential correlates of housing affordability stress.
      RESULTS: Almost 5% of Australians aged 55 years and older, and 20% of those
      younger than 55 years, are estimated to experience housing affordability stress.
      Men and women living alone are more likely to experience affordability stress
      when compared to couples. Low-income earners, those with a consumer debt or who
      do not hold assets, are at a heightened risk of such stress. Home ownership,
      regardless of income, is the strongest buffer against housing affordability
      problems in old age. CONCLUSION: Although the prevalence of housing affordability
      stress is low among older Australians when compared to the younger population, a
      definite social gradient exists in those at risk.

PMID- 18713212
TI  - Widowhood and self-rated health among Chinese elders: the effect of economic
      condition.
AB  - OBJECTIVE: To examine the mediating effect of economic condition (income, work
      status, self-rated financial situation and financial support) on widowhood and
      self-rated health in elderly Chinese. METHODS: The study sample consists of
      17,556 married and widowed elders age 60 and older selected from the nationwide
      2000 Sample Survey on Aged Population in Urban/Rural China. Path analysis is used
      to identify the direct and indirect relationships of economic condition between
      widowhood and self-rated health. RESULTS: Widowhood has a direct effect on self
      rated health for those widowed for more than 4 years. Work status and perceived
      financial situation mediate that relationship regardless of length of time
      widowed. Being older, male, less educated, and functionally healthy are
      associated with better self-rated health among those widowed. CONCLUSIONS: Work
      status and perceived financial situation have a more significant effect on
      widowhood and self-rated health than income and financial support. The findings
      have cross-cultural implications for developing elder care programs.

PMID- 18713213
TI  - Measuring changes in activity participation of older Australians: validation of
      the Activity Card Sort-Australia.
AB  - OBJECTIVES: This study explored the psychometric properties of the Australian
      version of the Activity Card Sort (ACS-Aus), a recently developed measure of
      activity participation for use with older adults. Concurrent, convergent
      construct, and discriminative construct validity were examined. METHODS: The
      study included 93 Australian adults aged 60-95 years. Participants completed the
      ACS-Aus, as well as an existing Australian measure of activity participation (The
      Adelaide Activities Profile) and an Australian measure of subjective well-being
      (the Personal Well-being Index). RESULTS: The ACS-Aus demonstrated moderate
      concurrent validity (r = 0.434), moderate convergent construct validity (r =
      0.354), and strong discriminative validity (P = 0.000). CONCLUSIONS: The World
      Health Organization has recently promoted participation as an important component
      of the healthy ageing process. This study has validated the use of the ACS-Aus in
      measuring participation of community-dwelling older adults in Australia.

PMID- 18713214
TI  - Home care clients' participation in fall prevention activities.
AB  - OBJECTIVE: To determine whether home care clients have accessed or been
      influenced by fall prevention programs. METHODS: Mail survey of 4743 home care
      clients from several home care agencies. RESULTS: Among the clients, 47.2%
      completed the survey and 46% had fallen within the last year. Faller and non
      fallers differed in attitude to falls and fall risk factors. Only 15% of fallers
      and 7% of non-fallers had taken part in a fall prevention program and only 8%
      knew how to access information about such activities. CONCLUSIONS: Fall
      prevention strategies should be targeted at the home care population. Such
      programs should take into consideration the specific needs of this group.

PMID- 18713215
TI  - Inpatient multidisciplinary rehabilitation after hip fracture for residents of
      nursing homes: a randomised trial.
AB  - OBJECTIVE: To determine the effectiveness of interdisciplinary rehabilitation for
      women with hip fracture who were residents of nursing homes. DESIGN: Randomised
      controlled trial. SUBJECTS: Eleven cognitively impaired women with hip fracture
      who were previously ambulant. METHODS: Participants were randomly allocated to
      usual care (discharge back to the nursing home soon after surgery to the hip
      fracture) or an inpatient interdisciplinary rehabilitation program. RESULTS:
      Participants were severely cognitively impaired and the majority used a walking
      aid prior to fracturing their hip. There was one early death, and at final follow
      up (4 months after hip fracture) median (range) Barthel Index was 28 (0-82) for
      control group and 68 (0-88) for the intervention group. CONCLUSION: No definite
      conclusion can be drawn about the effectiveness of the intervention because of
      its premature termination. However, the study established that it is feasible to
      provide an interdisciplinary rehabilitation for older people with hip fracture
      and severe disablement.

PMID- 18713216
TI  - Developing recommendations for implementing the Australian Pain Society's pain
      management strategies in residential aged care.
AB  - OBJECTIVE: This study aimed to develop recommendations and a related
      implementation resource 'toolkit' to facilitate implementation of pain management
      strategies in Australian Residential Aged Care Facilities (RACFs). METHODS: This
      qualitative study used written materials, focus groups and individual interviews
      to gather data from participants. Thirty-four health-care professionals with
      experience in the aged care sector were recruited from five Western Australian
      RACFs. General practitioners who had an interest in aged care were contacted via
      local general practice networks. RESULTS: Findings indicated that focused
      education sessions were needed to support implementation. A tailored toolkit was
      developed to assist the process. Funding and workforce constraints were found to
      be threats to complete implementation in some facilities. CONCLUSIONS: A
      multifaceted approach is needed to promote the implementation of pain management
      strategies in RACFs. In particular, unlicensed care workers, who may have
      responsibility for recognising and reporting signs of pain, require further
      education to support their role in the pain management process.

PMID- 18713224
TI  - A comparison of the effects of propofol and etomidate on the induction of
      anesthesia and on cardiopulmonary parameters in dogs.
AB  - OBJECTIVE: To determine the effects of propofol or etomidate on induction
      quality, arterial blood pressure, blood gases, and recovery quality in normal
      dogs. STUDY DESIGN: Randomized, blinded trial. ANIMALS: Eighteen purpose-bred
      adult Beagles. METHODS: Dogs were randomly assigned to receive propofol at 8 mg
      kg(-1) or etomidate at 4 mg kg(-1) intravenously (IV) administered to effect.
      Midazolam was administered at 0.3 mg kg(-1) IV as pre-medication at least 1
      minute prior to induction. Direct arterial blood pressure, arterial blood gases,
      and heart rate were obtained at baseline, before induction, after induction, and
      for every 5 minutes afterwards until the dog began to swallow and the trachea was
      extubated. The dogs were allowed to breathe room air with the endotracheal tube
      in place. RESULTS: The systolic arterial pressure (SAP) was higher in the
      etomidate group compared with the propofol group after induction. The SAP and
      mean arterial pressure (MAP) were higher in the etomidate group compared with the
      propofol group at 5 minutes. The recovery quality and ataxia score were worse in
      the etomidate group compared with the propofol group. Time from extubation to
      sternal recumbency and sternal recumbency to standing was longer in the etomidate
      group compared with the propofol group. The heart rate, PaCO(2), and HCO(3) were
      higher in the propofol group compared with the etomidate group after induction.
      The PaO(2) and SaO(2) were lower in the propofol group compared with the
      etomidate group after induction. The SAP and MAP were lower in the propofol group
      at 5 minutes compared with baseline. CONCLUSION AND CLINICAL RELEVANCE: Propofol
      caused a decrease in SAP and MAP which was not observed with etomidate. Etomidate
      caused longer and poorer recoveries than propofol.

PMID- 18713225
TI  - Anesthetic and cardiopulmonary effects of intramuscular morphine, medetomidine,
      ketamine injection in dogs.
AB  - OBJECTIVE: To determine the quality and duration of anesthesia and the
      cardiopulmonary effects of a morphine, medetomidine, ketamine (MMK) combination
      administered intramuscularly (IM) to dogs. STUDY DESIGN: Descriptive injectable
      anesthetic protocol evaluation. ANIMALS: Eight intact adult Beagle dogs: five
      males, three females. METHODS: The electrocardiogram, heart rate, direct arterial
      blood pressure, and core body temperature were monitored in eight chronically
      instrumented dogs. Each dog received 0.2 mg kg(-1) morphine sulfate, 20 microg
      kg(-1) medetomidine hydrochloride, and 5 mg kg(-1) ketamine hydrochloride IM.
      Anesthetic and analgesic effects (clamping the tail and metatarsus) were
      categorized, and the times to lateral recumbency, orotracheal intubation,
      extubation, and sternal recumbency were recorded. Respiratory, cardiovascular,
      temperature, and acid-base variables were recorded 5 minutes before, and 3, 10,
      20, 30, 45, 50, and 60 minutes after MMK. Atipamezole, 100 microg kg(-1) IM, was
      administered 60 minutes after MMK administration and data recorded 10 minutes
      later. RESULTS: The onset of anesthesia was uneventful and rapid. Time to lateral
      recumbency was 7.1 +/- 4.1 minutes. The tracheas of four dogs were orally
      intubated in 5.1 +/- 0.8 minutes. After MMK administration most dogs were
      unresponsive to noxious stimulation from 20 to 60 minutes and heart rate, cardiac
      index and venous blood pH were significantly decreased from baseline values.
      Arterial blood pressure increased initially and then returned to baseline values.
      Times to extubation (four dogs) and return to sternal recumbency after
      atipamezole administration were 2.8 +/- 1.8 and 4.3 +/- 4.4 minutes,
      respectively. CONCLUSION: The IM administration of MMK produced anesthesia and
      analgesia in Beagle dogs. Hemodynamic data were within accepted normal values.
      Atipamezole administration produced rapid return to consciousness in all dogs.
      CLINICAL RELEVANCE: Morphine/medetomidine/ketamine may be used for minor medical
      and surgical procedures requiring short-term anesthesia and analgesia but it is
      not recommended for medical procedures that are painful.

PMID- 18713226
TI  - Recovery of horses from general anesthesia in a darkened or illuminated recovery
      stall.
AB  - OBJECTIVE: To assess whether recovery from general anesthesia, in an illuminated
      or a darkened stall, has an effect on time to first movement, time to standing,
      and recovery score. STUDY DESIGN: Prospective randomized clinical study. ANIMALS:
      Twenty-nine healthy, 2- to 5-year-old horses undergoing surgical correction of
      dorsal displacement of the soft palate. METHODS: Each horse was assigned randomly
      to recover in either an illuminated (n = 15) or a darkened stall (n = 14). For
      pre-anesthetic medication, all horses received intravenous (IV) xylazine (0.4 mg
      kg(-1)) and butorphanol (0.02 mg kg(-1)). Anesthesia was induced with midazolam
      (0.1 mg kg(-1)) and ketamine (2.2 mg kg(-1)) IV and maintained on isoflurane in
      oxygen. Vital parameters, end-tidal CO(2) and isoflurane were recorded at 5
      minute intervals. At the conclusion of anesthesia, horses were placed in either
      an illuminated or a darkened stall and xylazine (0.2 mg kg(-1)) IV was
      administered at extubation. Video cameras were used to record the horses while
      they were allowed to recover undisturbed. Video recordings were later viewed and
      recoveries were evaluated on a 100-point scale by three graders. RESULTS: Horses
      in illuminated and darkened recovery stalls were evaluated on total anesthesia
      time, minimum alveolar concentration hours of isoflurane, time to first movement,
      time to standing, and total recovery score. There were no significant differences
      between the two groups in any of the measured parameters. CONCLUSION: Recovering
      horses in a darkened versus an illuminated recovery stall may provide no benefit.
      CLINICAL RELEVANCE: Darkening the recovery stalls for horses recovering from
      general anesthesia may be unnecessary.

PMID- 18713227
TI  - Hansen's disease in Portugal: multibacillary patients treated between 1988 and
      2003.
AB  - BACKGROUND: There is an estimate low incidence of patients with Hansen's disease
      in Portugal. Following the 1982 World Health Organization (WHO) recommendations,
      extended multidrug therapy (MDT) was started for multibacillary (MB) patients.
      Patients were then treated with rifampicine (RFP), clofazimine (CLF) and dapsone
      (DDS) for a minimum of 2 years or until smear negativity. The aim of this study
      was to evaluate MDT efficacy in our patient population. METHODS: Retrospective
      and descriptive study of 102 MB patients who underwent MDT from 1988 to 2003.
      RESULTS: The number of new MB patients has gradually increased since 1960, the
      first year of our consultation, due mostly to a rise in imported cases. Overall,
      34% of the subjects were immigrants, mainly from former Portuguese Colonies.
      Forty-six patients had previously received monotherapy with DDS (mean duration of
      this treatment, 22 years). Relapse after MDT occurred in 9 cases (8.8%), but
      importantly, all relapsed cases were smear negative at least on one occasion
      after the end of treatment, suggesting these were true relapses rather than
      treatment failures. CONCLUSIONS: Despite the 2-year WHO-MDT regimen, patients
      with MB disease clearly face the possibility of relapse. We propose that any
      reduction in the duration of therapy such as the recently proposed 6-month
      standard MDT is likely to increase the relapse rate even further. Important
      issues for future consideration are the needs to identify those at risk of
      relapse and in need of alternative antimicrobial treatment with a prolonged
      clinical follow-up.

PMID- 18713228
TI  - Combination of short- and long-pulsed mode of electro-optical synergy technology
      for photoepilation: a retrospective study with short- and long-term follow-up.
AB  - BACKGROUND: The dual-energy technology of ELOS showed promising results for
      photoepilation of dark as well as blond and white hairs; however, only few
      studies exist on this topic. Objective To assess the short- and long-term effect
      of an electro-optical synergy device for photoepilation. MATERIALS AND METHODS:
      We carried out a retrospective study on 24 patients with unwanted facial hair.
      Each area was treated consecutively with two passes using a combined-energy
      system [intense pulsed light (680-980 nm)/bipolar radiofrequency]. The short-term
      results were assessed semiquantitatively by three independent dermatologists
      based on photographs taken before and after treatment; evaluation of long-term
      results was based on a telephone questionnaire. RESULTS: After a mean of 5.2
      treatments and 3.2 months follow-up, 22.2% of the treatment areas showed no/poor
      clearance, 28.9% moderate, 46.7% good and 2.2% excellent. Similar results were
      seen in thin and thick hair as well as fair and dark hair. After a period of 2
      years, eight patients were satisfied with the results and did not wish any
      further treatment. Ten patients continued treatment with an electro-optical
      synergy device: After an average of 3.6 sessions, 70% of them were satisfied with
      the results. Five patients ceased treatment because the success did not meet
      their expectations. CONCLUSIONS: Two passes with this combined-energy system are
      an effective treatment option for the removal of thin, thick, fair and dark hair;
      however, the system has no significant advantages over other available methods of
      photoepilation.

PMID- 18713229
TI  - Incidence of erythromelalgia: a population-based study in Olmsted County,
      Minnesota.
AB  - OBJECTIVE: To estimate the population-based incidence of erythromelalgia.
      Background Only one report describing the incidence of erythromelalgia has been
      published previously. STUDY DESIGN: A population-based analysis of data from the
      Rochester Epidemiology Project. SETTING: Tertiary care medical centre in Olmsted
      County, Minnesota (a rural county in the south-eastern portion of the state).
      PATIENTS: Thirty-three residents of Olmsted County with a diagnosis of
      erythromelalgia during the study period. METHODS: Age- and sex-specific incidence
      rates of erythromelalgia were determined. INTERVENTION: None. MAIN OUTCOME:
      Population-based incidence rate. RESULTS: The overall age- and sex-adjusted
      incidence rate (95% confidence interval, 95% CI) was 1.3 (0.8-1.7) per 100,000
      people per year. The incidence of primary and secondary erythromelalgia was 1.1
      (0.7-1.5) and 0.2 (0.02-0.4) per 100,000 people per year, respectively. The age
      adjusted incidence rates (95% CI) were 2.0 (1.2-2.7) per 100,000 women and 0.6
      (0.1-1.1) per 100,000 men. The study was limited by the small sample size and
      potential variability in recognition of erythromelalgia. CONCLUSION: The
      population-based incidence of erythromelalgia has increased with each decade in
      Olmsted County over the past three decades; overall incidence was 1.3 per 100,000
      people per year, approximately 5 times higher than previously reported.

PMID- 18713230
TI  - Cutaneous events during treatment of chronic inflammatory joint disorders with
      anti-tumour necrosis factor alpha: a cross-sectional study.
AB  - BACKGROUND: Anti-tumour necrosis factors (anti-TNF) are more and more used, but
      the rate of skin adverse events is not known. OBJECTIVE: The aim was to assess
      the number of skin infections and other dermatoses in patients treated with anti
      TNFalpha. PATIENTS AND METHODS: One hundred eighty-seven patients suffering from
      rheumatoid arthritis or ankylosing spondylitis underwent a dermatological exam.
      Patients with anti-TNF were compared with those without this treatment in a
      prospective transversal study. RESULTS: Among them, 59 patients were treated with
      anti-TNFalpha and steroids were prescribed in 100 cases. There was no difference
      in the prevalence of skin infections or eczema or tumours. Skin drug reactions
      were observed in six patients. Infections by dermatophytes appear very frequent,
      approaching 70% in both groups. CONCLUSIONS: This study shows that skin
      infections (or other skin diseases) are not more frequent in these patients. No
      differences were observed in infections (bacterial fungal, parasital or viral),
      tumours, psoriasis or the manifestations of atopic dermatitis. Nonetheless, a
      long-term survey might be interesting, especially about skin tumours.

PMID- 18713231
TI  - The role of human herpesvirus 6, human herpesvirus 7, Epstein-Barr virus and
      cytomegalovirus in the aetiology of pityriasis rosea.
AB  - AIM: To identify the role of human herpesvirus 6 (HHV-6), HHV-7, Epstein-Barr
      virus (EBV) and cytomegalovirus (CMV) in the pathogenesis of pityriasis rosea
      (PR). MATERIAL: Polymerase chain reaction with specific primers for HHV-6 and HHV
      7 DNA sequences was performed on the blood and tissue samples of 25 patients with
      PR and on the blood samples of age- and sex-matched healthy controls. HHV-6, EBV,
      CMV immunoglobulin M (IgM) and IgG were analysed by enzyme-linked immunosorbent
      assay, HHV-7 IgM and IgG were analysed by indirect immunofluorescence on the
      serum samples of the study population. In the patient group, the values were
      studied 2 weeks later again (second control). RESULTS: There were no differences
      between the first and second controls of the patients and healthy subjects
      regarding HHV-6 IgM, HHV-7 IgM, CMV IgM, EBV IgM results. There were significant
      differences between the first [HHV-6 DNA (2 of 25), HHV-7 DNA (6 of 25)] and
      second control [HHV-6 DNA (1 of 25), HHV-7 DNA (11 of 25)] of the patients for
      the blood samples in favour of HHV-7. PR patients showed higher amounts of HHV-6
      and HHV-7 DNA positivity when compared with that of healthy subjects. HHV-7
      seemed to be more important regarding tissue samples [HHV-6 DNA (7 of 25), HHV-7
      DNA (12 of 25) first control, HHV-6 DNA (6 of 25), HHV-7 DNA (12 of 25) second
      control] as well as blood samples. CONCLUSION: Though our results failed to
      support a causal relationship among EBV, CMV and PR, they indicated a possible
      role for HHV-6 and especially HHV-7 in a group of Turkish patients but other
      aetiological factors may exist.

PMID- 18713232
TI  - Calcium dobesilate for the treatment of erectile dysfunction in men with diabetes
      mellitus.
AB  - Calcium dobesilate has shown to improve endothelial function. This proof-of
      concept clinical trial was done to check whether it may improve erectile
      dysfunction in diabetic men. Male diabetic patients with a diagnosis of erectile
      dysfunction were randomized to receive either calcium dobesilate 1 g twice per
      day or placebo for 6 weeks. The International Index of Erectile Function (IIEF)
      was chosen as the primary efficacy measurement. Statistical procedures included a
      pre-scheduled adaptive interim analysis to recalculate sample size. Relevant, but
      not significant differences in the mean change from baseline in the primary end
      point (IIEF questions 3, 4 and 7) favouring dobesilate with respect to placebo
      were observed. Such differences reached statistical significance in some
      secondary end-points, including IIEF global as well as the erectile function and
      intercourse satisfaction domains' scores. Some patients experienced an important
      placebo effect. Results suggest that dobesilate may be of help to treat diabetic
      erectile dysfunction. Co-administration with phosphodiesterase inhibitors
      warrants further investigation. 

PMID- 18713233
TI  - Physiologically motivated time-delay model to account for mechanisms underlying
      enterohepatic circulation of piroxicam in human beings.
AB  - The study was conducted to formulate a physiologically motivated time-delay (PM
      TD) mathematical model for human beings, which incorporates disintegration of a
      drug formulation, dissolution, discontinuous gastric emptying and enterohepatic
      circulation (EHC) of a drug. Piroxicam, administered to 24 European, healthy
      individuals in 20 mg capsules Feldene Pfizer, was used as a model drug. Plasma
      was analysed for piroxicam by a validated high-performance liquid chromatography
      method. The PM TD mathematical model was developed using measured plasma
      piroxicam concentration-time profiles of the individuals and tools of a
      computationally efficient mathematical analysis and modeling, based on the theory
      of linear dynamic systems. The constructed model was capable of (i) quantifying
      different fractions of the piroxicam dose sequentially disposable for absorption
      and (ii) estimating time delays between time when the piroxicam dose reaches
      stomach and time when individual of fractions of the piroxicam dose is disposable
      for absorption. The model verification was performed through a formal proof,
      based on comparisons of observed and model-predicted plasma piroxicam
      concentration-time profiles. The model verification showed an adequate model
      performance and agreement between the compared profiles. Accordingly, it
      confirmed that the developed model was an appropriate representative of the
      piroxicam fate in the individuals enrolled. The presented model provides valuable
      information on factors that control dynamic mechanisms of EHC, that is,
      information unobtainable with the models proposed for the EHC analysis
      previously.

PMID- 18713234
TI  - Endoluminal norepinephrine inhibits smooth muscle activity of the pig pyeloureter
      by stimulation of beta-adrenoceptors without side effects.
AB  - It has been demonstrated in pigs that endoluminal administration of
      norepinephrine reduces the increase in renal pelvic pressure during perfusion.
      The purposes were to describe concentration-response relationship and receptor
      mechanism of the effect of norepinephrine on muscle function of pyeloureter and
      to reveal possible side effects on cardiovascular and renal functions. Renal
      pelvis was perfused, while pelvic pressure, cardiovascular and renal functional
      parameters were recorded. In group A, a pelvic pressure increase was examined
      during pressure flow studies with norepinephrine solutions (0, 1, 5, 50 and 100
      microg/ml). In group B, pelvis was perfused with 6 ml/min. norepinephrine
      solutions (0, 0.001, 0.01, 0.1 and 1 microg/ml). In group C, pelvis was perfused
      with 6 ml/min. norepinephrine, norepinephrine + sotalol 10(-) (6) mol/l and
      norepinephrine + phentolamine 10(-) (6) mol/l. Norepinephrine solutions of 0, 10(
      ) (8), 10(-) (7), 10(-) (6), 10(-) (5) and 10(-) (4) mol/l were used. In group A,
      all norepinephrine solutions lowered the pelvic pressure increase significantly.
      Large increases in plasma and urine norepinephrine occurred with 50 and 100
      microg/ml, but cardiovascular and renal functions remained unchanged. In group B,
      a significant diminishing pelvic pressure increase with all solutions was seen
      with a significant difference between all solutions. In group C, norepinephrine
      demonstrated a concentration-response curve with EC(50) between 10(-) (8) and 10(
      ) (7) mol/l (10(-) (7.27+/-0.40)). Sotalol had a smooth muscle inhibitory effect
      on the pyeloureter and inhibited the effect of norepinephrine increasing EC(50)
      by about a factor 10 (10(-) (6.40+/-1.17)). No convincing effect of phentolamine
      was observed. Endoluminal norepinephrine probably stimulates beta-adrenoceptors
      and inhibits a renal pelvis pressure increase to perfusion in a dose-related way
      without side effects. Endoluminal norepinephrine is safe in pigs and may be
      useful under endoscopy of the pyeloureter.

PMID- 18713235
TI  - Prevalence of oral herpes simplex virus reactivation in cancer patients: a
      comparison of different techniques of viral detection.
AB  - BACKGROUND: Oral reactivation of latent Herpes simplex virus (HSV) infection may
      easily occur in cancer patients. Virus reactivation can cause oral mucosa damage,
      worsen already existing lesions caused by stomatotoxic effect of cancer therapy
      and, whether symptomatic or asymptomatic, ample spreading and promote viral
      transmission. METHODS: Polymerase chain reaction (PCR), cell-culture and direct
      immunofluorescence have been used to determine the frequency of oral HSV
      reactivation in 60 patients undergoing chemotherapy for different malignancies.
      RESULTS: By means of PCR, the presence of viral DNA was detected in 71.7% of
      patients prior to chemotherapy and in 85.0% after chemotherapy. 33.3% of patients
      before and 40.0% after chemotherapy were viral-culture positive, while 3.3% of
      patients before and 11.7% after chemotherapy were positive as shown by direct
      immunofluorescence. No significant difference in HSV-1 reactivation was found
      before and after chemotherapy. In addition, no significant difference was found
      when comparing HSV-1 reactivation in patients with and without mucositis. HSV-2
      was not detected in any of the patients. CONCLUSIONS: Reactivation of latent HSV
      is exceptionally frequent in cancer patients. The results of this study suggest
      that virus reactivation occurs independently of cancer chemotherapy. The
      potential role of HSV reactivation in oral mucosa damage remains unclear.

PMID- 18713236
TI  - Light and scanning electron microscopic study on the lingual papillae and their
      connective tissue cores of the Cape hyrax Procavia capensis.
AB  - We examined the epithelial surface and connective tissue cores (CTCs) of each
      lingual papilla on the Paenungulata, Cape hyrax (Procavia capensis), by scanning
      electron microscopy and light microscopy. The tongue consisted of a lingual apex,
      lingual body and lingual root. Filiform, fungiform and foliate papillae were
      observed on the dorsal surface of the tongue; however, fungiform papillae were
      quite diminished on the lingual prominence. Moreover, no clearly distinguishable
      vallate papillae were found on the tongue. Instead of vallate papillae, numerous
      dome-like large fungiform papillae were arranged in a row just in front of the
      rather large foliate papillae. Foliate papillae were situated in the one-third
      postero-lateral margin of the lingual body. The epithelium of filiform papillae
      was covered by a keratinized layer with kerato-hyaline granules, whereas weak
      keratinization was observed on the interpapillary epithelium. The external
      surface of the filiform papillae was conical in shape. CTCs of the filiform
      papillae were seen as a hood-like core with a semicircular concavity in the
      anterior portion of each core. Large filiform papillae were distributed on the
      lingual prominence. The CTCs of large filiform papillae after exfoliation of
      their epithelium consisted of a concave primary core and were associated with
      several small protrusions. The surface of fungiform papillae was smooth and dome
      like. After removal of the epithelium, CTCs appeared as a flower bud-like primary
      core and were associated with several protrusions that were arranged on the rim
      of the primary core. Several taste buds were found on the top of the dorsal part
      of the epithelium of both fungiform and large fungiform papillae. Well-developed
      foliate papillae were seen and numerous taste buds could be observed in the
      lateral wall of the epithelium in a slit-like groove. The morphological
      characteristics of the tongue of the Cape hyrax had similarities with other
      Paenungulata such as Sirenia. However, three-dimensional characteristics,
      especially CTCs of lingual papillae, exhibited multiple similarities with
      rodents, insectivores and artiodactyls.

PMID- 18713238
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 18713239
TI  - Premating isolation is determined by larval rearing substrates in cactophilic
      Drosophila mojavensis. VIII. Mating success mediated by epicuticular hydrocarbons
      within and between isolated populations.
AB  - We tested the hypothesis that intrademic sexual selection has caused sexual
      isolation between populations of geographically isolated populations of
      cactophilic Drosophila mojavensis, and was mediated by epicuticular hydrocarbons
      (EHCs), contact pheromones in this system. Sexual selection and sexual isolation
      were estimated using a Baja California and mainland population by comparing the
      number of mated and unmated males and females in each of four pairwise population
      mating trials. EHC profiles were significantly different in mated and unmated
      males in the interdemic (Bajafemale symbol x Mainlandmale symbol and
      Mainlandfemale symbol x Bajamale symbol), but not the intrademic mating trials. A
      small number of EHCs was identified that best discriminated among mated and
      unmated males, mostly alkadienes with 34 and 37 carbons. Females showed
      population-specific preferences for male EHC profiles. However, EHC profiles
      between mated and unmated males in the intrademic mating trials were not
      significantly different, consistent with undetectable sexual selection estimated
      directly from numbers of copulating pairs vs. unmated adults. Thus, sexual
      isolation among populations was much stronger than sexual selection within these
      populations of D. mojavensis.

PMID- 18713240
TI  - Maternal allocation strategies and differential effects of yolk carotenoids on
      the phenotype and viability of yellow-legged gull (Larus michahellis) chicks in
      relation to sex and laying order.
AB  - Egg quality may mediate maternal allocation strategies according to progeny sex.
      In vertebrates, carotenoids have important physiological roles during embryonic
      and post-natal life, but the consequences of variation in yolk carotenoids for
      offspring phenotype in oviparous species are largely unknown. In yellow-legged
      gulls, yolk carotenoids did not vary with embryo sex in combination with egg
      laying date, order and mass. Yolk lutein supplementation enhanced the growth of
      sons from first eggs but depressed that of sons from last eggs, enhanced survival
      of daughters late in the season, and promoted immunity of male chicks and chicks
      from small eggs. Lack of variation in egg carotenoids in relation to sex and egg
      features, and the contrasting effects of lutein on sons and daughters, do not
      support the hypothesis of optimal sex-related egg carotenoid allocation.
      Carotenoids transferred to the eggs may rather result from a trade-off between
      opposing effects on sons or daughters.

PMID- 18713241
TI  - The oxidation handicap hypothesis and the carotenoid allocation trade-off.
AB  - The oxidation handicap hypothesis proposes that testosterone mediates the trade
      off between the expression of secondary sexual traits and the fight against free
      radicals. Coloured traits controlled by testosterone can be produced by
      carotenoid pigments (yellow-orange-red traits), but carotenoids also help to
      quench free radicals. Recently, it has been shown that testosterone increases the
      amount of circulating carotenoids in birds. Here, a testosterone-mediated trade
      off in the carotenoid allocation between colour expression and the fight against
      oxidative stress is proposed. Male red-legged partridges were treated with
      testosterone, anti-androgens or manipulated as controls. Testosterone-treated
      males maintained the highest circulating carotenoid levels, but showed the palest
      red traits and no evidence of oxidative damage. Increased levels of a key
      intracellular antioxidant (i.e. glutathione) indicated that an oxidative
      challenge was in fact induced but controlled. The trade-off was apparently solved
      by reducing redness, allowing increased carotenoid availability, which could have
      contributed to buffer oxidative stress.

PMID- 18713242
TI  - Small effective population sizes in two planktonic freshwater copepod species
      (Eudiaptomus) with apparently large census sizes.
AB  - In small planktonic organisms, large census sizes (N(c)) suggest large effective
      population sizes (N(e)), but reliable estimates are rare. Here, we present
      N(e)/N(c) ratios for two freshwater copepod species (Eudiaptomus sp.) using
      temporal samples of multilocus microsatellite genotypes and a pseudo-likelihood
      approach. N(e)/N(c) ratios were very small in both Eudiaptomus species (10(-7)
      10(-8)). Although we hypothesized that the species producing resting eggs (E.
      graciloides) had a larger N(e) than the other (E. gracilis), estimates were not
      statistically different (E. graciloides: N(e) = 672.7, CI: 276-1949; E. gracilis:
      N(e) = 1027.4, CI: 449-2495), suggesting that the propagule bank of E.
      graciloides had no detectable influence on N(e).

PMID- 18713243
TI  - The stimulation of immune defence accelerates development in the red flour beetle
      (Tribolium castaneum).
AB  - The timing of the transition between life stages is of key importance for an
      organism. Depending on the environmental conditions, maturing earlier at a
      smaller size or maturing later at a larger size can be advantageous for fitness.
      Exposure to parasites and subsequent immune activation may lead to alterations in
      development. Immune defence often comes at a cost, such as energy drain towards
      immune function, which is likely to delay development. On the other hand, animals
      may react to an anticipated risk of infection with a phenotypically plastic shift
      in life history, which may more likely lead to accelerated development and
      earlier maturation. We tested these alternatives in the red flour beetle,
      Tribolium castaneum. Young larvae were exposed to a non-infectious immune
      challenge with heat-killed bacteria (either Escherichia coli or Bacillus
      thuringiensis) and they were followed up for their development, survival, adult
      size and reproduction. We found that animals that had experienced a bacterial
      challenge developed into adults earlier than sham-treated beetles, while they did
      not differ significantly in survival or adult size. Beetles exposed to E. coli
      produced fewer offspring, while exposure to B. thuringiensis did not affect
      offspring number. Taken together, our results indicate that T. castaneum is able
      to speed up its development when facing a risk of infection.

PMID- 18713244
TI  - Evolution of grasping among anthropoids.
AB  - The prevailing hypothesis about grasping in primates stipulates an evolution from
      power towards precision grips in hominids. The evolution of grasping is far more
      complex, as shown by analysis of new morphometric and behavioural data. The
      latter concern the modes of food grasping in 11 species (one platyrrhine, nine
      catarrhines and humans). We show that precision grip and thumb-lateral behaviours
      are linked to carpus and thumb length, whereas power grasping is linked to second
      and third digit length. No phylogenetic signal was found in the behavioural
      characters when using squared-change parsimony and phylogenetic eigenvector
      regression, but such a signal was found in morphometric characters. Our findings
      shed new light on previously proposed models of the evolution of grasping.
      Inference models suggest that Australopithecus, Oreopithecus and Proconsul used a
      precision grip.

PMID- 18713245
TI  - Maximal and submaximal endurance performance in adults with severe haemophilia.
AB  - Maximal exercise testing, including the determination of maximal performance and
      maximal oxygen uptake (VO(2max)), is considered the gold standard for assessing
      maximal endurance performance. The effectiveness of such testing is often reduced
      in haemophilic adults owing to musculoskeletal impairments or pain rather than
      because of cardiac exertion. The measurement of submaximal performance parameters
      overcomes many limitations of maximal exercise testing but a testing standard is
      still lacking. The aim of this study was to investigate maximal and particularly
      submaximal endurance performance of adult patients with severe haemophilia A and
      B. Eleven patients and 11 matched healthy controls were tested by spiroergometry
      with a specific treadmill test and the power was calculated in Watts. The
      haemophilic group achieved lower absolute (210 +/- 63 W) and weight-related (2.94
      +/- 0.98 W kg(-1)) maximal endurance performance compared with the control group
      (287 +/- 50 W resp. 3.82 +/- 0.53 W kg(-1); P </= 0.05). The patients also showed
      a lower submaximal endurance performance at the individual anaerobic threshold
      (IAT = 147 +/- 56 W) and fixed lactate values (2 mmol = 98 +/- 60 W; 4 mmol = 158
      +/- 56 W) compared with the healthy controls (IAT = 210 +/- 41 W; 2 mmol = 153 +/
      30 W; 4 mmol = 223 +/- 39 W; all P </= 0.05). The heart rate and lactate value
      at the IAT were not different. The disease-related musculoskeletal changes in
      haemophilic adults lead to a reduced maximal and submaximal endurance
      performance, which can be easily measured by the described test procedure.

PMID- 18713246
TI  - Clinical outcome of moderate haemophilia compared with severe and mild
      haemophilia.
AB  - Information on outcome and treatment of patients with moderate haemophilia is
      scarce. In this study, we compared self-reported burden of disease in moderate
      haemophilia to severe and mild haemophilia. A nationwide questionnaire on
      bleeding pattern, treatment, impairment and quality of life was sent to 1567
      Dutch patients with haemophilia. Out of 1066 respondents (response rate: 68%),
      16% had moderate, 44% severe and 39% mild haemophilia. Median age was 36 years.
      Although overall outcome in moderate haemophilia was in between severe and mild
      haemophilia, moderate haemophilia patients did report a substantial burden of
      disease. The majority of patients with moderate haemophilia (73%) reported bleeds
      in the previous year; and a considerable proportion of moderate patients reported
      joint impairment (43%), chronic pain (15%), needed orthopaedic aids (24%) or were
      unemployed because of disability (27%). Within the group of moderate haemophilia
      patients, a large variation in bleeding pattern and outcome was observed. A
      quarter of patients with moderate haemophilia reported a more severe phenotype
      and intermittent use of prophylaxis. These patients reported frequent bleeding,
      with a median of eight bleeds per year, including two joint bleeds, and 68%
      reported joint impairment. IN CONCLUSION: Although outcome in moderate
      haemophilia is generally in between severe and mild haemophilia, moderate
      haemophilia patients reported a substantial burden of disease, and for more than
      25% of patients with moderate haemophilia long term prophylaxis was implemented
      because of frequent bleeds.

PMID- 18713247
TI  - A case of invasive carcinoma derived from intraductal papillary-mucinous
      carcinoma of the pancreas producing a signet ring-type appearance on pancreatic
      duct brushing cytology.

PMID- 18713248
TI  - Melanoma cells in voided urine cytology.

PMID- 18713249
TI  - Cervical smear adequacy: cellularity references were found to increase both
      interobserver agreement and unsatisfactory rate.
AB  - OBJECTIVES: To determine the degree of interobserver variation in the assessment
      of conventional cervical smear adequacy as defined by The Bethesda System (TBS)
      2001, and to determine the effect of using reference images of known squamous
      cellularity when performing squamous adequacy assessments. METHODS: Experimental
      pre-test/post-test design utilizing 70 conventionally prepared cervical smears.
      Sample smears containing scant squamous cellularity were independently rated on
      two occasions by six cytotechnologists. Time 1 was without the use of reference
      images, and Time 2 was aided by cellularity reference images. The kappa statistic
      was used to compare rater agreement. RESULTS: The level of agreement increased
      from an average kappa of 0.26 (SD 0.10) for Time 1, to an average kappa of 0.40
      (SD 0.15) for Time 2. The difference in mean kappa values at the two assessments
      was statistically significant (t = 3.71; P = 0.002). Unanimous agreement among
      the raters was observed for 15 samples (21.42%) at Time 1 (only one of which was
      classified as unsatisfactory) and 21 samples (30.00%) at Time 2 (12 of which were
      classified as unsatisfactory). CONCLUSION: Interobserver agreement increased
      after cellularity reference images were implemented. Using TBS 2001 squamous
      adequacy criteria and images of known squamous cellularity as references resulted
      in a decreased number of smears reported as satisfactory.

PMID- 18713250
TI  - Diagnostic pitfalls in the evaluation of fine needle aspiration cytology of the
      thyroid: correlation with histopathology in 260 cases.
AB  - OBJECTIVES: Fine needle aspiration cytology (FNAC) of the thyroid is a non
      invasive, cost-effective screening procedure that is valuable for distinguishing
      neoplastic lesions from non-neoplastic nodules. The aim of this study was to
      determine the diagnostic accuracy of FNACs performed at our institution by
      correlating FNAC results with histopathological diagnoses. METHODS: Two hundred
      and seventy-one aspiration cytology specimens followed by thyroidectomy were
      included in the study, and the results of 260 adequate FNACs were compared with
      their histological diagnoses. RESULTS: The sensitivity and specificity of thyroid
      FNAC for detecting neoplasia were 92.6% and 91.6%, respectively. There were 15
      (5.7%) false positives and six (2.3%) false negatives. CONCLUSIONS: The results
      showed that follicular cells that exhibit some of the features of papillary
      carcinoma could be observed in a cytology slide of Hashimoto's thyroiditis,
      leading to a diagnostic pitfall. In addition, cellularity and overlapping
      cytological criteria in hyperplasia might lead to a false diagnosis.

PMID- 18713251
TI  - Cytological assessment of conventional transbronchial fine needle aspiration of
      lymph nodes.
AB  - OBJECTIVES: Transbronchial fine needle aspiration (TBNA) is a minimally invasive
      bronchoscopic technique that allows pathological examination of mediastinal and
      hilar lymph nodes. The aim of this study was to assess the cytopathological
      outcome of TBNA. METHODS: One hundred and eighty-seven patients who underwent
      TBNA of mediastinal and hilar lesions from May 2000 to June 2007 were reviewed.
      RESULTS: TBNA results were considered to be adequate if the cytological material
      revealed a malignant lesion or sufficient number of benign lymphoid cells. In the
      current study, 40 cases (21.9%) were reported as inadequate. When inadequate
      tests were excluded, the overall sensitivity and accuracy of TBNA in the
      diagnosis of malignant lesions were 83.5% and 88.0% respectively. The lowest
      sensitivity was noted in lymph node involvement by lymphoma. Regarding the
      workload associated with TBNA cytology, we found that the average number of
      conventionally prepared cytological slides per case was high (17 slides per
      case). CONCLUSION: Our results confirm that conventional TBNA is a sensitive and
      useful technique but it is relatively expensive and the protocols should be
      adapted to allow appropriate material to be collected for ancillary diagnostic
      tests.

PMID- 18713252
TI  - Fine needle aspiration of a huge pelvic mass involving the iliac bone.

PMID- 18713253
TI  - Characterisation of haematological profiles and low risk of thromboembolic events
      with bortezomib in patients with relapsed multiple myeloma.
AB  - Haematological toxicities and thromboembolic (TE) events are common complications
      of myeloma therapy. TE risk may be elevated with combination regimens, notably
      thalidomide/lenalidomide plus high-dose dexamethasone; concomitant erythropoietin
      appears to further increase the risk with lenalidomide-dexamethasone. We
      characterised thrombocytopenia and neutropenia in the phase 3 APEX (Assessment of
      Proteasome Inhibition for Extending Remissions) study of bortezomib versus high
      dose dexamethasone in relapsed myeloma, and calculated the incidences of deep
      vein thrombosis (DVT)/pulmonary embolism (PE) with: bortezomib or dexamethasone
      +/- erythropoietin in APEX; bortezomib +/- dexamethasone +/- erythropoietin in
      two phase 2 studies of relapsed/refractory myeloma. Bortezomib-associated
      thrombocytopenia and neutropenia were transient, predictable and manageable; mean
      platelet and neutrophil counts followed a cyclical pattern, and improved over the
      treatment course. Grade 3/4 thrombocytopenia incidence was higher with bortezomib
      versus dexamethasone (26%/4% vs. 5%/1%), but significant bleeding events were
      comparable (4% vs. 5%). DVT/PE incidence was low (< or =3.1%) in all analyses;
      addition of dexamethasone/erythropoietin did not affect TE risk. In APEX, TE risk
      appeared lower with bortezomib versus dexamethasone. Bortezomib caused transient
      and cyclical thrombocytopenia and was not associated with elevated TE risk, alone
      or with dexamethasone +/- erythropoietin. Preliminary data suggest bortezomib may
      reduce the thrombogenic potential of combination regimens via inhibition of
      platelet function or other mechanism-specific effects on coagulation.

PMID- 18713254
TI  - A possible inhibitory action of diaminodiphenyl sulfone on tumour necrosis factor
      alpha production from activated mononuclear cells on cutaneous lupus
      erythematosus.
AB  - BACKGROUND: We have previously reported that diaminodiphenyl sulfone (DDS;
      dapsone) can bring about significant clinical improvement in patients with
      cutaneous lupus erythematosus (CLE). However, the pharmacological actions of DDS
      in the skin lesion of patients with CLE are still unknown. OBJECTIVE: In this
      study, we aimed to clarify the pharmacological actions of DDS on CLE. METHODS: We
      conducted an in vitro study to examine the effects of DDS on the mRNA expression
      and production of cytokines on lipopolysaccharide-stimulated peripheral blood
      mononuclear cells. Results. DDS suppressed mRNA expression of tumour necrosis
      factor (TNF)-alpha and significantly decreased the level of TNF-alpha in culture
      supernatant. CONCLUSIONS: DDS may exert an anti-inflammatory action by
      suppressing TNF-alpha produced by activated mononuclear cells.

PMID- 18713255
TI  - Clinical heterogeneity in recessive epidermolysis bullosa due to mutations in the
      keratin 14 gene, KRT14.
AB  - BACKGROUND: Epidermolysis bullosa simplex (EBS), the most common subtype of EB,
      is usually inherited as an autosomal dominant trait caused by mutations in either
      the keratin 5 (KRT5) or keratin 14 (KRT14) genes. Recessive EBS (R-EBS) is
      extremely rare. METHODS: We present the first Australian patient diagnosed with R
      EBS, to our knowledge, and a comprehensive review of genotypes and phenotypes of
      R-EBS reported cases. RESULTS: The female proband, of Turkish descent with
      consanguineous parentage, was referred to us at the age of 8 years. Clinically,
      she had a severe phenotype including generalized blisters, mucosal involvement
      and EB naevi. Immunofluorescence mapping and electron microscopy were consistent
      with a diagnosis of EBS. Staining for Keratin 14 (K14) was negative. The basal
      layer, however, reacted with monoclonal antibodies to keratins 6 (K6) and 16
      (K16). Mutation screening from genomic DNA showed that the proband was homozygous
      for the truncation mutation Y204X in exon 3 of KRT14, and both unaffected parents
      were heterozygous for a single KRT14 Y204X mutation. The phenotype of our patient
      is reported in more detail and with longer follow-up than those of others
      published in the literature. DISCUSSION: The proband's phenotype was severe as an
      infant but improved with age, suggesting that an alternative keratin is pairing
      with K5 in her skin to compensate for the loss of K14--a novel biological
      compensatory mechanism. It is interesting that K6 and K16 were expressed, as
      these are normally positive in hyperproliferative skin disorders.

PMID- 18713256
TI  - MicroRNAs in development and disease.
AB  - Since the discovery of microRNAs (miRNAs) in Caenorhabditis elegans, mounting
      evidence illustrates the important regulatory roles for miRNAs in various
      developmental, differentiation, cell proliferation, and apoptosis pathways of
      diverse organisms. We are just beginning to elucidate novel aspects of RNA
      mediated gene regulation and to understand how heavily various molecular pathways
      rely on miRNAs for their normal function. miRNAs are small non-protein-coding
      transcripts that regulate gene expression post-transcriptionally by targeting
      messenger RNAs (mRNAs). While individual miRNAs have been specifically linked to
      critical developmental pathways, the deregulated expression of many miRNAs also
      has been shown to have functional significance for multiple human diseases, such
      as cancer. We continue to discover novel functional roles for miRNAs at a rapid
      pace. Here, we summarize some of the key recent findings on miRNAs, their mode of
      action, and their roles in both normal development and in human pathology. A
      better understanding of how miRNAs operate during the normal life of a cell as
      well as in the pathogenesis of disease when deregulated will provide new avenues
      for diagnostic, prognostic, and therapeutic applications.

PMID- 18713257
TI  - MicroRNA epigenetic alterations: predicting biomarkers and therapeutic targets in
      human diseases.
AB  - MicroRNAs (miRNAs) consist of a class of evolutionarily conserved small non
      coding RNA that regulates target messenger RNAs by mechanisms such as incomplete
      base pairing and post-transcriptional gene silencing. Recent studies have shown
      that aberrant miRNA expression is a common feature of many human disorders
      including aging, heart diseases, cancer, autoimmune diseases and others. It seems
      likely that miRNA expression levels can be used as novel diagnostic markers.
      MiRNAs may also provide a new strategy for therapeutic interventions. In this
      review, we focus on recent advances in understanding how miRNA changes contribute
      to disease development and their potential as novel biomarkers and therapeutic
      targets for human diseases.

PMID- 18713259
TI  - Short-term clinical effects of adjunctive antimicrobial photodynamic therapy in
      periodontal treatment: a randomized clinical trial.
AB  - OBJECTIVE: The aim of this study was to assess the effect of adjunctive
      antimicrobial photodynamic therapy (aPDT) in chronic periodontitis. MATERIAL AND
      METHODS: Twenty patients with untreated chronic periodontitis were included. All
      teeth received periodontal treatment comprising scaling and root planing. Using a
      split-mouth design, two quadrants (test group) were additionally treated with
      aPDT. Sulcus fluid flow rate (SFFR) and bleeding on probing (BOP) were assessed
      at baseline, 1 week and 3 months after treatment. Relative attachment level
      (RAL), probing depths (PDs) and gingival recession (GR) were evaluated at
      baseline and 3 months after treatment. RESULTS: Baseline median values for PD, GR
      and RAL were not different in the test group and control group. Values for RAL,
      PD, SFFR and BOP decreased significantly 3 months after treatment in the control
      group (median delta RAL: -0.35 mm, inter-quartile range: 0.21 mm), with a higher
      impact on the sites treated with adjunctive aPDT (median delta RAL: -0.67 mm,
      inter-quartile range: 0.36 mm, p<0.05). GR increased 3 months after treatment
      with and without adjunctive aPDT (p<0.05), with no difference between the groups
      (p>0.05). CONCLUSIONS: In patients with chronic periodontitis, clinical outcomes
      of conventional subgingival debridement can be improved by adjunctive aPDT.

PMID- 18713258
TI  - Dimensional changes of the alveolar ridge contour after different socket
      preservation techniques.
AB  - OBJECTIVES: The aim of the following study was to assess contour changes after
      socket preservation techniques. MATERIAL AND METHODS: In five beagle dogs, the
      distal root of the third and fourth mandibular premolars was extracted. The
      following treatments (Tx) were randomly assigned for the extraction socket. Tx 1:
      BioOss Collagen. Tx 2: BioOss Collagen and a free soft tissue graft. Tx 3: No
      treatment. Tx 4: The internal buccal aspect was covered with an experimental
      collagen membrane, the extraction socket was filled with BioOss Collagen and the
      membrane folded on top of the graft. Impressions were obtained at baseline, 2 and
      4 months after surgery. Bucco-lingual measurements were performed using digital
      imaging analysis. RESULTS: All groups displayed contour shrinkage at the buccal
      aspect. Only the differences between the two test groups (Tx 1, Tx 2) and the
      control group (Tx 3) were significant at the buccal aspect (p< or =0.001). No
      measurements of the Tx 4 group could be performed. CONCLUSION: Socket
      preservation techniques, used in the present experiment, were not able to
      entirely compensate for the alterations after tooth extraction. Yet,
      incorporation of BioOss Collagen seems to have the potential to limit but not
      avoid the post-operative contour shrinkage.

PMID- 18713260
TI  - The significance of subclinical rejection.
AB  - Subclinical rejection (SCR) is quite common early following renal transplantation
      and decreases progressively with time. The immunological profile of the
      recipient, the immunosuppressive regimen used, and the occurrence of prior
      episodes of clinical acute rejection (AR) are all risk factors for SCR. SCR, in
      turn, is a risk factor for chronic interstitial and tubular fibrosis and has been
      associated with worse glomerular filtration rate (GFR) and graft survival. Early
      SCR should be initially treated with pulse steroids. SCR is a form of biopsy
      proven AR and, particularly if treated, must be fairly reported and displayed as
      a solid endpoint in clinical studies.

PMID- 18713261
TI  - Clinical improvement of nephrogenic systemic fibrosis after kidney
      transplantation.
AB  - Nephrogenic systemic fibrosis (NSF) has been observed with increased frequency in
      recent years. Progressive hardening of the skin advancing to severe woody
      induration and the development of thickened hyperpigmented plaques on the
      extremities and the trunk are the main clinical features. Further progression of
      the disease results in flexion contractures of the upper and lower extremities,
      resulting in immobilization and severe morbidity. In this study, we reviewed our
      experience with seven end-stage renal disease patients who were referred to our
      center between January 2004 and June 2005 for kidney transplant evaluation or for
      diagnosis and treatment of their deteriorating condition. Diagnosis in all
      patients was confirmed by skin and muscle biopsy. Three of these patients
      underwent renal transplantations, and softening of the skin and improved mobility
      of the joints was noted after kidney transplantation. Three of the four patients
      who remained on dialysis showed further deterioration of their NSF despite a
      trial of immunosuppressive therapy. Improvement after transplantation could be
      secondary to immunosuppression, increased renal clearance and/or more effective
      fluid management.

PMID- 18713262
TI  - Urinary tract reconstruction using the controlateral native ureter and a combined
      open-retroperitoneoscopic approach after renal transplantation.
AB  - An alternative technique for urinary tract (UT) reconstruction is described in a
      renal transplant recipient who developed a severe stenosis of the graft ureter.
      This approach entails the retroperitoneoscopic preparation of the native ureter
      contralateral to the graft, followed by an open reconstruction of the UT. The
      ureter was dissected along its entire length to the level of the iliac vessels,
      with its associated mesentery still attached in order to preserve the vascular
      supply. The corresponding native kidney contralateral to the graft was
      endoscopically removed. A longitudinal sub-umbilical incision allowed the
      excision of the stenotic tract and the reconstruction of the UT by means of a
      manual end-to-end anastomosis between the new ureter and the graft pelvis. No
      post-operative complications occurred and renal function immediately resumed. The
      approach described represents an alternative solution for the surgical management
      of severe ureteric graft stenosis. We believe that the magnification of the
      anatomy granted by the endoscope during the dissection of the ureter and
      neighboring structures provides the gentle handling of the tissues and the remote
      dissection away from the ureter with the highest precision.

PMID- 18713263
TI  - Severe veno-occlusive disease after autologous peripheral blood stem cell
      transplantation for high-grade non-Hodgkin lymphoma: report of a successfully
      managed case and a literature review of veno-occlusive disease.
AB  - Veno-occlusive disease (VOD) of the liver is a severe complication of high-dose
      chemotherapy and allogeneic or autologous stem cell transplantation with
      potential fatal outcome. We report a case of severe VOD in a patient with a high
      grade B-cell lymphoma. Liver-venule occlusion was confirmed by liver biopsy.
      Supportive care, fibrinolytic treatment with recombinant tissue plasminogen
      activator and defibrotide maintenance therapy led to complete resolution of VOD
      demonstrated at liver biopsy and with a follow-up of 44 months after autologous
      peripheral blood stem cell transplantation. The literature on VOD has been
      reviewed.

PMID- 18713264
TI  - The evolving notion of "senior" kidney transplant recipients.
AB  - The maximum age of recipients expected to benefit with a kidney transplant has
      increased in the past three decades. In 1980, patients older than age 50 were not
      listed for a transplant. In 2004, almost 90% aged 50-60 yr with end-stage renal
      disease were listed, and some were even older than age 80. We summarize previous
      articles to illustrate how the notion of "senior" has evolved for kidney
      transplantation, and using data reported to the Organ Procurement Transplant
      Network, describe characteristics, treatments and outcomes in recipients older
      than 50 yr. Fractions of male, white, non-obese, unsensitized recipients and use
      of expanded criteria donors increased in cohorts with increasing recipient age.
      The percentage of recipients with hypertension or diabetes decreased, but the
      percentage with cancer increased. The fraction spared steroids increased with
      increasing age, but other aspects of immunosuppression were not remarkably
      different. No differences in early outcomes were notable, and elderly recipients
      likely did not return to dialysis. However, both graft and patient survival rates
      decreased with increasing age. Although a small fraction was selected, and
      survival rates were lower, patients older than 80 yr received kidney transplants.

PMID- 18713265
TI  - Immunosuppression without calcineurin inhibition: optimization of renal function
      in expanded criteria donor renal transplantation.
AB  - INTRODUCTION: To assess the efficacy of calcineurin inhibitor (CNI)-free
      immunosuppression vs. calcineurin-based immunosuppression in patients receiving
      expanded criteria donor (ECD) kidneys. PATIENT AND METHODS: Thirteen recipients
      of ECD kidneys were enrolled in this pilot study and treated with induction
      therapy and maintained on sirolimus, mycophenolate mofetil (MMF) and prednisone.
      A contemporaneous control group was randomly selected comprised of 13 recipients
      of ECD kidneys who had been maintained on CNI plus MMF and prednisone. RESULTS:
      For the study group vs. the control group, two-yr graft survival was 92.3% vs.
      84.6% (p = NS), two-yr patient survival was 100% vs. 92.3% (p = NS) and the acute
      rejection rates were 23% vs. 31% (p = NS), respectively. Renal function was
      significantly better in the study group compared with control up to the six-month
      mark, after which, it remained numerically but not statistically significant.
      Complications were more common in the study group, but serious adverse events
      requiring discontinuation were rare. CONCLUSION: This pilot study demonstrates
      that CNI-free regimens can be safely implemented in patients receiving ECD
      kidneys with excellent two-yr patient and graft survival and good renal allograft
      function. Longer follow-up in larger randomized controlled trials are necessary
      to establish these findings.

PMID- 18713266
TI  - Predictor factors for the development of arterial hypertension following heart
      transplantation.
AB  - INTRODUCTION: Up to 95% of the patients with heart transplantation (HT) suffer
      from arterial hypertension (AHT). The development of de novo AHT after HT has not
      been greatly studied. AIM: To identify the predictor variables for the
      development of de novo AHT after HT. MATERIALS AND METHODS: We retrospectively
      studied 253 patients with HT and who did not previously have AHT. We excluded
      cases of early mortality, re-transplants and combined transplants. We considered
      AHT as the constant need to take anti-hypertensive drugs to maintain blood
      pressure < 140/90 mmHg. We studied all the variables relating to recipient,
      donor, surgical procedure, immunosuppression and follow-up. The statistics used
      were the Student's t-test, chi-square statistic and a logistic regression
      analysis. RESULTS: Of the 253 patients, 109 (43%) developed AHT. The variables
      associated with more prevalent AHT were male recipient/donor, idiopathic dilated
      cardiomyopathy (IDCM) as cause of HT, having been a smoker as well as renal
      deterioration (RD) and hypercholesterolemia after HT. The multivariate analysis
      found smoking prior to the HT and hypercholesterolemia during follow-up as
      independent risk factors and urgent HT as a protective variable. CONCLUSIONS: AHT
      after HT is frequent. The variables associated in our population were smoking
      before HT, male recipient/donor, IDCM prior to HT and hypercholesterolemia and RD
      after HT.

PMID- 18713267
TI  - A pitfall in screening with decoy cells after simultaneous pancreas kidney
      transplantation.
AB  - In this report, we describe a bladder-drained simultaneous pancreas-kidney
      transplant (SPKT) recipient with a polyoma virus-associated nephropathy (PVAN) in
      whom the urine cytology failed to detect decoy cells despite repeated attempts.
      Several tests were performed to confirm our hypothesis that pancreatic enzymes
      can degrade decoy cells and granulocytes. This case illustrates an important
      pitfall in the urinary screening for PVAN with cytology and for urinary tract
      infections with urine sediment in bladder-drained SPKT recipients.

PMID- 18713268
TI  - Laparoscopic gastric banding in a kidney-pancreas transplant recipient with new
      onset type II diabetes mellitus associated with morbid obesity.
AB  - Combined kidney-pancreas transplantation is the treatment of choice for end-stage
      diabetic nephropathy. Post-transplant weight gain increases the risk for post
      transplant complications and death owing to cardiovascular events. Gastric
      banding is an established treatment for moderate morbid obesity. We report on a
      patient who experienced significant weight gain and developed type II diabetes
      mellitus following successful kidney-pancreas transplantation. He underwent
      laparoscopic gastric banding and initially had good weight loss. However, lack of
      compliance with dietary guidelines led to transient failure of weight loss
      therapy. With further adjustment of the gastric band good weight loss was
      achieved.

PMID- 18713269
TI  - Why is the choice of future climate scenarios for species distribution modelling
      important?
AB  - Species distribution models (SDMs) are common tools for assessing the potential
      impact of climate change on species ranges. Uncertainty in SDM output occurs due
      to differences among alternate models, species characteristics and scenarios of
      future climate. While considerable effort is being devoted to identifying and
      quantifying the first two sources of variation, a greater understanding of
      climate scenarios and how they affect SDM output is also needed. Climate models
      are complex tools: variability occurs among alternate simulations, and no single
      'best' model exists. The selection of climate scenarios for impacts assessments
      should not be undertaken arbitrarily - strengths and weakness of different
      climate models should be considered. In this paper, we provide bioclimatic
      modellers with an overview of emissions scenarios and climate models, discuss
      uncertainty surrounding projections of future climate and suggest steps that can
      be taken to reduce and communicate climate scenario-related uncertainty in
      assessments of future species responses to climate change.

PMID- 18713270
TI  - Subsidy hypothesis and strength of trophic cascades across ecosystems.
AB  - Ecosystems are differentially open to subsidies of energy, material and
      organisms. This fundamental ecosystem attribute has long been recognized but the
      influence of this property on community regulation has not been investigated. We
      propose that this environmental attribute may explain variation in the strength
      of trophic cascades among ecosystems. Simply because of gravity, we should
      predict that systems with convex profiles receive low amounts of subsidies
      whereas systems with concave profiles act as spatial attractors, and receive high
      amounts of subsidies. The subsidy hypothesis states that ecosystems with high
      amounts of allochthonous inputs will experience the strongest trophic cascades.
      To test this hypothesis, we derive ecosystem models and investigate the effect of
      location and magnitude of subsidies on the strength of trophic cascades.
      Predictions from our models support the subsidy hypothesis and highlight the need
      to consider ecosystems as open to allochthonous flows.

PMID- 18713271
TI  - The need for speed: informed land acquisitions for conservation in a dynamic
      property market.
AB  - Land acquisition is a common approach to biodiversity conservation but is
      typically subject to property availability on the public market. Consequently,
      conservation plans are often unable to be implemented as intended. When
      properties come on the market, conservation agencies must make a choice: purchase
      immediately, often without a detailed knowledge of its biodiversity value; survey
      the parcel and accept the risk that it may be removed from the market during this
      process; or not purchase and hope a better parcel comes on the market at a later
      date. We describe both an optimal method, using stochastic dynamic programming,
      and a simple rule of thumb for making such decisions. The solutions to this
      problem illustrate how optimal conservation is necessarily dynamic and requires
      explicit consideration of both the time period allowed for implementation and the
      availability of properties.

PMID- 18713272
TI  - The species composition of the human intestinal microbiota differs between
      particle-associated and liquid phase communities.
AB  - Many of the substrates available as energy sources for microorganisms in the
      human colon, including dietary plant fibre and secreted mucin, are insoluble. It
      seems likely that such insoluble substrates support a specialized microbiota, and
      in order to test this hypothesis, faecal samples from four healthy subjects were
      fractionated into insoluble (washed particulate) and liquid fractions. Analysis
      of 1252 PCR-amplified 16S rRNA sequences revealed a significantly lower
      percentage of Bacteroidetes (P = 0.021) and a significantly higher percentage of
      Firmicutes (P = 0.029) among bacterial sequences amplified from particle
      associated (mean 76.8% Firmicutes, 18.5% Bacteroidetes) compared with liquid
      phase (mean 65.8% Firmicutes, 28.5% Bacteroidetes). Within the Firmicutes, the
      most significant association with solid particles was found for relatives of
      Ruminococcus-related clostridial cluster IV species that include Ruminococcus
      flavefaciens and R. bromii, which together accounted for 12.2% of particle
      associated, but only 3.3% of liquid phase, sequences. These findings were
      strongly supported by microscopy, using group-specific FISH probes able to detect
      these species. This work suggests that the primary colonizers of insoluble
      substrates found in the gut are restricted to certain specialized groups of
      bacteria. The abundance of such primary degraders may often be underestimated
      because of the difficulty in recovering these bacteria and their nucleic acids
      from the insoluble substrate.

PMID- 18713274
TI  - Effect of porto-systemic shunting on NOS expression after extended hepatectomy in
      rats.
AB  - AIM: Several surgical procedures have been developed for reducing portal vein
      pressure to prevent postoperative liver injury. Nitric oxide synthase expression
      (NOS) induced by elevation of portal vein pressure is thought to play an
      important role in liver regeneration, but the details are not well understood.
      METHODS: Rats in the control group and in the subcutaneous splenic transposition
      (SST) group underwent 90% partial hepatectomy. Survival and portal vein pressure
      were analyzed. The serum IL-6 and TNF-alpha levels were measured by enzyme-linked
      immunosorbent assay (ELISA). Hepatocyte proliferation and apoptosis 12 hours
      after hepatectomy were analyzed immunohistochemically. The protein and messenger
      RNA expression of inducible and endothelial NOS were analyzed using Western
      blotting and quantitative reverse transcriptase polymerase chain reaction,
      respectively. RESULTS: The survival rate of the SST group was significantly
      higher. Portal vein pressure, TNF-alpha level and the apoptotic index were
      significantly lower in the SST group. Twelve hours after surgery, liver inducible
      NOS (iNOS) protein expression was significantly lower in the SST group. However,
      protein expression of endothelial NOS was not significantly different between the
      groups. CONCLUSION: Inducible NOS expression after extended hepatectomy is
      related to the effects of porto-systemic shunting on the splanchnic circulation.
      Also, iNOS induction and concomitant nitric oxide generation appear to
      participate in the cytotoxicity of excessive portal pressure after extended
      hepatectomy.

PMID- 18713273
TI  - Intracutaneous injection of the macrophage-activating lipopeptide-2 (MALP-2)
      which accelerates wound healing in mice--a phase I trial in 12 patients.
AB  - Chronic skin ulcers, such as leg ulcers, pressure sores and diabetic foot ulcers,
      are a challenge to physicians and medical personnel and a cause of tremendous
      discomfort and ensuing loss of quality of life to the patients. Wound healing
      involves production and action of various growth factors. A novel approach,
      distinct from the application of single growth factors, is the administration of
      the macrophage stimulator macrophage-activating lipopeptide-2 (MALP-2). The
      rationale is based on the finding that macrophages are the main source of several
      growth factors required for wound healing, which are sequentially released during
      this process. MALP-2 has previously been shown to be effective in an established
      animal model with diabetic mice. The purpose of the present phase I study was to
      establish tolerability of MALP-2 when applied into small cutaneous wounds in
      human beings. Twelve patients (six females and six males; mean age 66.8 years;
      range 52-87 years) with different diagnoses were enrolled into the study. An
      artificial wound was created with a 2-mm diameter skin biopsy punch and a volume
      of 30 microl MALP-2 (0.125-1 microg) or vehicle control, respectively, was
      injected intracutaneously into the wound and closed with a water-resistant
      transparent adhesive. Photos were taken daily from every patient up to 6 days,
      and skin biopsies were performed after 1 week from six patients. We could show in
      the present study for the first time that MALP-2 caused a transient erythema and
      was tolerated without any systemic side effects up to a dose of 1 microg per
      wound in human beings. In healthy as well as in diabetic patients, MALP-2 induced
      local inflammation that faded after 48 h. The effectiveness of MALP-2 in the
      healing of chronic wounds in humans, e.g. in chronic skin ulcers, such as leg
      ulcers, pressure sores and diabetic foot ulcers, could now be addressed in
      further studies.

PMID- 18713275
TI  - Frequency and distribution of hepatitis B virus genotypes among eastern Indian
      voluntary blood donors: Association with precore and basal core promoter
      mutations.
AB  - AIM: To screen hepatitis B virus (HBV) genotypes and associated basal core
      promoter (BCP; T1762/A1764) and precore (PreC; A1896) mutations among the HBV
      surface antigen (HBsAg) positive voluntary blood donors in eastern India.
      METHODS: HBV genotypes, BCP and PreC mutations of 141 HBsAg positive voluntary
      blood donors were determined by the restriction fragment length polymorphism
      (RFLP) method and a phylogenetic tree was constructed from surface (S) gene
      region sequences of representative HBsAg positive donors to confirm the results.
      RESULTS: HBV/D was the most predominant (79, 56.0%) genotype followed by HBV/C
      (33, 23.4%) and HBV/A (29, 20.6%). HBV/C infected blood donors are mostly young
      (18-25 years). The occurrence of BCP mutation was found to be significantly
      higher in HBV/C (24, 72.7%) than in HBV/A (7, 24.1%, P < 0.001) and HBV/D (17,
      21.5%, P < 0.001), whereas PreC mutation was more frequent in HBV/D (28, 35.4%)
      than in HBV/C (9, 27.3%). However, the simultaneous presence of BCP and PreC
      mutations was more common in HBV/C (8/33, 24.2%), followed by HBV/D (6/79, 7.6%).
      CONCLUSION: In addition to HBV/D and HBV/A, a significant proportion of HBV/C
      (23.4%) was also present among the voluntary blood donors from eastern India,
      most frequently in the 18-25 year age group. BCP mutation was more common in
      HBV/C infected donors.

PMID- 18713276
TI  - Liver regeneration is impaired by FK778 in partially hepatectomized rats, while
      supplemental uridine restores both liver growth and hepatocyte proliferation.
AB  - AIM: The impact of mandatory immunosuppression on liver regeneration after
      segmental liver transplantation is of clinical importance. FK778, a novel
      immunosuppressant, inhibits pyrimidine biosynthesis and prevents rejection after
      organ transplantation in a dose-dependent manner. We investigated the effect of
      FK778 at a highly effective dose on liver regeneration in a small animal model.
      METHODS: Inbred Lewis rats were subjected to 70% partial hepatectomy (PH) and
      treated with saline (n = 28), uridine (n = 16), FK778 alone (n = 28) or in
      combination with uridine (n = 16). FK778 was given intravenously daily at a dose
      of 25 mg/kg bodyweight (bw) and uridine was given daily intraperitoneally at a
      dose of 250 mg/kg bw. Liver bodyweight ratio (LBR), hepatocyte proliferation
      index (PI), blood chemistry and morphological analysis were incorporated. PI was
      determined by Ki-67 immunostaining. De Ritis ratio was calculated to assess the
      extent of liver damage. RESULTS: In FK778-treated animals PI was decreased at 24
      h and 72 h and LBR was lower at 48 h and 72 h (P < 0.05) after the PH. In
      addition, morphological analysis showed confluent central lobular necrosis at 72
      h in four of seven animals. Uridine supplementation restored PI, LBR and the de
      Ritis ratio in FK778-treated animals and no confluent necroses were observed.
      CONCLUSION: FK778 is antihepatotrophic as well as antiproliferative during rat
      liver regeneration. Both liver growth and hepatocyte proliferation are completely
      restored by supplementation with uridine. In addition, supplemental uridine
      markedly reduces the severity of morphological abnormalities consistent with
      FK778 toxicity.

PMID- 18713277
TI  - Hepatic oxidant/antioxidant status in cholesterol-fed rabbits: Effects of garlic
      extract.
AB  - AIM: The investigation of oxidant/antioxidant status in hepatic tissues from
      cholesterol-fed rabbits and the establishment of possible protective effects of
      aqueous garlic extract on cholesterol-induced hepatic steatosis. METHODS: Twenty
      two of 31 white New Zealand rabbits were given cholesterol (0.5 g/kg/day) for 4
      months. Seven of them were then killed (cholesterol group). The remaining 15
      animals were divided into two groups. Seven were fed on a normal laboratory diet
      (normal diet group) and the others (extract group) on a normal diet plus garlic
      extract (1.5 ml/kg/day) for an additional 3 months. Superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px), catalase (CAT) enzyme activities, antioxidant
      potential (AOP) value, malondialdehyde (MDA), cholesterol and triglyceride levels
      in the liver tissues and total cholesterol and triglyceride levels in serum
      samples were measured. An histological evaluation was also done. RESULTS: An
      impaired antioxidant system, reduced antioxidant defence potential and increased
      peroxidation were found in hepatic steatotic tissues from cholesterol-fed
      animals. Treatment with garlic extract caused a significant increase in
      antioxidant potential and partly eliminated peroxidation damage in the hepatic
      tissue. Additionally, the extract caused significant reductions in the
      cholesterol levels of blood and hepatic tissues. The histological evaluations
      were in accordance with these results. CONCLUSION: The results suggest that
      cholesterol-induced steatosis leads to a weakened antioxidant defence system and
      causes peroxidation in the hepatic tissue. Treatment with garlic extract may
      contribute to significant amelioration in the hepatic steatosis and peroxidation
      processes.

PMID- 18713278
TI  - In vivo interferon system assessed by 2'-5' oligoadenylate synthetase activity in
      chronic hepatitis C virus patients treated with pegylated interferon and
      ribavirin.
AB  - AIM: 2',5' oligoadenylate synthetase (2-5AS), an enzyme induced by interferon, is
      an accurate indicator of the antiviral effect of interferon. We measured it
      during pegylated interferon based therapies in patients with chronic hepatitis C
      virus (HCV) in order to determine the dynamics of antiviral status in vivo and
      the relationship between the response to exogenous interferon and the outcome of
      therapy. METHODS: A total of 160 patients with chronic HCV were treated with
      pegylated interferon alfa 2a or 2b or non-pegylated interferon, with or without
      ribavirin. Serum 2-5AS activity was measured by radioimmunoassay assay kits every
      2 weeks. RESULTS: In 60 patients treated with pegylated interferon alfa 2a or 2b,
      2-5AS levels increased to 7-40 times (average 235 pmol/dL) above the pretreatment
      levels (30 pmol/dL), which were significantly higher than the levels during non
      pegylated interferon therapy. Ribavirin did not enhance 2-5AS levels. 2-5AS
      levels between sustained virological response (SVR) and non-SVR, including null
      responders to pegylated interferon plus ribavirin therapy were not significantly
      different. CONCLUSION: 2-5AS levels were significantly higher in patients treated
      with pegylated interferon than in those treated with non-pegylated interferon,
      suggesting that pegylated interferon is more potent at inducing interferon
      response genes resulting in an improved antiviral effect. Ribavirin did not
      appear to be related to interferon response gene induction.

PMID- 18713279
TI  - The effects of N-acetylcysteine on the expression of matrix metalloproteinase-2
      and tissue inhibitor of matrix metalloproteinase-2 in hepatic fibrosis in bile
      duct ligated rats.
AB  - AIM: N-acetylcysteine can inhibit the formation of intracellular reactive oxygen
      intermediates. Cellular redox state plays a role in regulating the secretion of
      matrix metalloproteinase-2. We investigated the effects of N-acetylcysteine on
      the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix
      metalloproteinase-2. METHODS: Bile duct ligated rats were used as a model of
      hepatic fibrosis. We compared the level of gene expression (using real-time
      reverse transcription polymerase chain reaction [RT-PCR]), liver function
      parameters, hepatic reactive oxygen production, lipid peroxidation and
      glutathione state in experimental groups. RESULTS: N-acetylcysteine treatment
      significantly improved liver function parameters including the plasma levels of
      aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase
      and bilirubin. In addition, significant improvement of glutathione state and
      reactive oxygen production were observed. Hepatic lipid peroxidation was reversed
      by N-acetylcysteine treatment. Although N-acetylcysteine treatment did not
      completely normalize the increased matrix metalloproteinase-2 expression, it
      significantly decreased its level by 65%. N-acetylcysteine treatment also
      significantly decreased matrix metalloproteinase-2 activity and normalized tissue
      inhibitor of matrix metalloproteinase-2 expression. CONCLUSION: Collectively, N
      acetylcysteine showed inhibition of matrix metalloproteinase-2 expression and
      activity. In addition, administration of N-acetylcysteine was associated with
      downregulation of the expression of tissue inhibitor of matrix metalloproteinase
      2 and amelioration of oxidative stress in the liver of bile duct ligated rats.

PMID- 18713280
TI  - Determination of antimicrobial resistance and virulence gene signatures in
      surface water isolates of Escherichia coli.
AB  - AIMS: To determine the occurrence of Escherichia coli harbouring virulence
      markers of shiga- or entero-toxins and resistance to antimicrobials in surface
      waters. METHODS AND RESULTS: Surface water samples were collected at six
      locations of the river Gomti. E. coli isolates (n = 90) were characterized for
      their pathogenic potential using polymerase chain reaction to detect virulence
      genes as well as their sensitivity to antimicrobial agents using disc diffusion
      methods. In this study, 57.8% of E. coli isolates exhibited resistance to three
      or more antimicrobial agents. Sensitivity to cephotaxime, gentamicin and
      norfloxacin was observed in 7.8%, 48.9% and 77.8% of isolates, respectively. Both
      stx1 and stx2 genes were present in 15.6% of isolates while remaining isolates
      had either stx1 (17.8%) or stx2 (6.7%). The stx1 gene (33.3%) was more prevalent
      than stx2 (22.2%). The results indicate that the LT1 and ST1 genes were positive
      in 21.2% of isolates. CONCLUSIONS: The presence of multi-drug resistance and
      virulence genes in E. coli isolated from surface water being used for domestic
      and recreational purposes may result in waterborne outbreaks. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The data will be useful in monitoring surface waters for
      forecasting and management of waterborne outbreaks.

PMID- 18713282
TI  - Cross-contamination in the kitchen: estimation of transfer rates for cutting
      boards, hands and knives.
AB  - AIMS: To quantify cross-contamination in the home from chicken to ready-to-eat
      salad. METHODS AND RESULTS: Based on laboratory scenarios performed by de Jong et
      al. (2008), transfer rates were estimated for Campylobacter jejuni and
      Lactobacillus casei as a tracer organism. This study showed that transfer
      characteristics for both micro-organisms were comparable when washing regimes and
      transfer via items (cutting board, hands and knives) were compared. Furthermore,
      the study showed that the use of separate transfer rates for transfer from
      chicken to items and from items to salad will lead to an overestimation of
      campylobacteriosis risk. Applying good hygienic practices resulted in final
      levels of bacteria in the salad below the detection limit. Our study showed that
      it is important to include these data points in model fitting. CONCLUSIONS:
      Results obtained in observational studies with Lact. casei can be translated to
      Camp. jejuni using the transfer rates obtained in this study. Cross-contamination
      by hands, cutting boards and knives was equally important. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Cross-contamination should be incorporated in
      microbiological risk assessments. The present study contributes to this by
      quantifying transfer of Camp. jejuni and Lact. casei from raw chicken via various
      contact surfaces into the ready-to-eat product.

PMID- 18713281
TI  - Lysogeny in Lactobacillus delbrueckii strains and characterization of two new
      temperate prolate-headed bacteriophages.
AB  - AIMS: Frequency of lysogeny in Lactobacillus delbrueckii strains (from commercial
      and natural starters) and preliminary characterization of temperate
      bacteriophages isolated from them. METHODS AND RESULTS: Induction of strains (a
      total of 16) was made using mitomycin C (MC) (0.5 mug ml(-1)). For 37% of the MC
      treated supernatants, it was possible to detect phage particles or presence of
      killing activity, but only two active bacteriophages were isolated. The two
      temperate phages isolated were prolate-headed phages which belonged to group c of
      Lact. delbrueckii bacteriophages classification. Different DNA restriction
      patterns were obtained for each phage, while the structural protein profiles and
      packaging sites were identical. Distinctive one-step growth curves were exhibited
      by each phage. An influence of calcium ions was observed for their lysis in broth
      but not on the adsorption levels. CONCLUSIONS: Our study showed that lysogeny is
      also present in Lact. delbrueckii strains, including commercial strains.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Commercial strains could be lysogenic and
      this fact has a great practical importance since they could contribute to the
      dissemination of active-phage particles in industrial environments.

PMID- 18713283
TI  - A citrate-inducible gene, encoding a putative tricarboxylate transporter, is
      downregulated by the organic solvent DMSO in Agrobacterium tumefaciens.
AB  - AIMS: To investigate the effects of the organic solvent dimethyl sulfoxide (DMSO)
      on the expression of a citrate-inducible gene, encoding a putative tricarboxylate
      transporter, in Agrobacterium tumefaciens. METHODS AND RESULTS: By two
      dimensional gel electrophoresis, we discovered a putative tricarboxylate
      transporter named ActC, whose expression was downregulated by DMSO. The
      expression of actC is also induced by tricarboxylates but not affected by other
      organic acids of the TCA cycle. Intriguingly, transcriptional activation of actC
      by citrate is compromised in the presence of DMSO. Furthermore, expression of
      actC is abolished by deletion of actDE, encoding a putative two-component
      regulatory system upstream of the actCBA gene cluster. CONCLUSIONS: actC is a
      citrate-inducible gene that is repressed by DMSO and whose expression is likely
      regulated by a two-component system. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study provides useful information as to a potential DMSO-regulatory system of A.
      tumefaciens or other soil bacteria when encountering DMSO in nature. In addition,
      DMSO-regulated genes should be taken into account for studies in which bacterial
      cultures were treated with compounds dissolved in DMSO.

PMID- 18713284
TI  - The growth limits of a large number of Listeria monocytogenes strains at
      combinations of stresses show serotype--and niche-specific traits.
AB  - AIMS: The aim of this study was to associate the growth limits of Listeria
      monocytogenes during exposure to combined stresses with specific serotypes or
      origins of isolation, and identify potential genetic markers. METHODS AND
      RESULTS: The growth of 138 strains was assessed at different temperatures using
      combinations of low pH, sodium lactate, and high salt concentrations in brain
      heart infusion broth. None of the strains was able to grow at pH < or = 4.4, a(w)
      < or = 0.92, or pH < or = 5.0 combined with a(w) < or = 0.94. In addition, none
      of the strains grew at pH < or = 5.2 and NaLac > or = 2%. At 30 degrees C, the
      serotype 4b strains showed the highest tolerance to low pH and high NaCl
      concentrations at both pH neutral (pH 7.4) and mild acidic conditions (pH 5.5).
      At 7 degrees C, the serotype 1/2b strains showed the highest tolerance to high
      NaCl concentrations at both pH 7.4 and 5.5. Serotype 1/2b meat isolates showed
      the highest tolerance to low pH in the presence of 2% sodium lactate at 7 degrees
      C. ORF2110 and gadD1T1 were identified as potential biomarkers for phenotypic
      differences. CONCLUSIONS: Differences in growth limits were identified between
      specific L. monocytogenes strains and serotypes, which could in some cases be
      associated with specific genetic markers. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Our data confirm the growth limits of L. monocytogenes as set out by the European
      Union for ready-to-eat foods and provides an additional criterion. The
      association of L. monocytogenes serotypes with certain stress responses might
      explain the abundance of certain serotypes in retail foods while others are
      common in clinical cases.

PMID- 18713285
TI  - Algorithm-based design of synthetic growth media stimulating virulence properties
      of Metarhizium anisopliae conidia.
AB  - AIMS: Synthetic media should be designed for the production of Metarhizium
      anisopliae conidia with improved virulence properties. METHODS AND RESULTS: A
      genetic algorithm (GA), demonstrated to be suitable for the design of media for
      spore mass production (Hutwimmer et al. 2008), was utilized for a multi-objective
      medium design to improve conidia yield and three proposed virulence properties of
      conidia: C : N ratio, germination speed and amount of spore-bound Pr1 protease.
      After five iterative optimizations, 52 media were improved over Sabouraud
      dextrose agar (SDA). Four media exhibited medium performances (a factor derived
      from the four single optimization variables) of around 0.7; cf. SDA = 0.532;
      media with enhanced properties were reached for each single optimization
      variable; Bioassays against Tenebrio larvae indicated also a slight improvement
      in virulence of conidia from designed media. A degenerated phenotype of the same
      strain did not exhibit differences in colony appearance, spore characteristics
      and virulence if grown on designed media. CONCLUSIONS: The application of a
      problem-oriented GA is a practical and rapid method to design media for multi
      objective purposes. SIGNIFICANCE AND IMPACT OF THE STUDY: The applicability of a
      GA for multi-objective medium design was demonstrated for the cultivation of
      anamorphic fungi on solid media.

PMID- 18713286
TI  - Autochthonous bacterial flora indicated by PCR-DGGE of 16S rRNA gene fragments
      from the alimentary tract of Costelytra zealandica (Coleoptera: Scarabaeidae).
AB  - AIMS: To locate and identify putative autochthonous bacteria within the grass
      grub gut that may have a role in symbiosis. METHODS AND RESULTS: Polymerase chain
      reaction-denaturing gradient gel electrophoresis (DGGE) fingerprinting was used
      to investigate bacterial diversity in the grass grub larval gut. The microbial
      community profiles from five geographically distinct populations were compared
      and the influence of feeding was analysed. Bacterial community in the midgut was
      highly variable between locations and was affected by feeding. The hindgut
      contained a more diverse but stable bacterial community that was less affected by
      external conditions. Forty-seven distinct DGGE bands, representing different
      bacterial genotypes, could be distinguished from all samples, with 34 different
      bands occurring in the hindgut. The 22 most common bands were isolated and DNA
      was sequenced. Sequence analysis revealed that most bacteria (16/22) were
      affiliated to the Clostridiales with the predominant bacteria affiliated to the
      genus Clostridium. The remaining bacteria were aligned to the Betaproteobacteria,
      Deltaproteobacteria and Bacteroidetes. CONCLUSIONS: The grass grub larva has an
      autochthonous microflora with predominance of Clostridium spp. in the hindgut.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Occurrence of an autocthonous microflora in
      the grass grub hindgut suggests a symbiotic relationship which could help explain
      the ability of larval scarabs to feed on recalcitrant organic matter.

PMID- 18713287
TI  - Recombinant Bacillus thuringiensis strain shows high insecticidal activity
      against Plutella xylostella and Leptinotarsa decemlineata without affecting
      nontarget species in the field.
AB  - AIMS: To construct a recombinant Bacillus thuringiensis (Bt) strain with broad
      insecticidal spectrum and investigate its impact on nontarget organisms in field.
      METHOD AND RESULTS: The cry-type gene of wild Bt strain UV17 was identified and a
      novel cry1Ba gene was cloned. The cry3Aa7 gene, which was highly toxic to
      coleopteran pests, was introduced into UV17, and a recombinant strain designated
      as UV173A was obtained. Bioassay results showed that UV173A was not only highly
      toxic against Plutella xylostella (50% lethal concentration [LC(50)] = 18.03
      microg ml(-1)), but also against coleopteran Leptinotarsa decernlineata (LC(50 )=
      0.19 mg ml(-1)). The recombinant strain was then tested in field trials to
      monitor its spatial variation of population and to investigate the impact on
      nontarget invertebrates. CONCLUSIONS: A recombinant Bt stain UV173A with broad
      insecticidal spectrum was obtained, and it did not cause adverse effects on the
      population of nontarget organisms. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      results obtained here indicated that cry1Ba3 gene may be useful for the
      resistance management of P. xylostella, and the recombinant stain UV173A was
      potential for field application against some crucifer vegetable pests as well as
      L. decemlineata.

PMID- 18713288
TI  - Regulation of hdc expression and HDC activity by enological factors in lactic
      acid bacteria.
AB  - AIMS: The aim of this work was to study the influence of enological factors on
      the histidine decarboxylase gene (hdc) expression and on histidine decarboxylase
      enzyme (HDC) activity in Lactobacillus hilgardii, Pediococcus parvulus and
      Oenococcus oeni. METHODS AND RESULTS: Cell extracts and whole cells were used.
      Glucose, fructose, malic acid and citric acid diminished the hdc expression.
      Ethanol did not increase hdc expression or activity in cells, but increased HDC
      activity. Temperature and pH had effect on the activity of HDC but not on hdc
      expression. Tartaric acid and l-lactic acid, and sulphur dioxide (SO(2)) had no
      effect on enzyme synthesis and activity. Bacterial species differ in the relative
      enzymatic activity but all the factors affected similarly to L. hilgardii, P.
      parvulus and O. oeni. CONCLUSIONS: The hdc gene expression was lowered by
      glucose, fructose, malic acid, and citric acid, whereas ethanol enhanced the HDC
      enzyme activity. The conditions that normally occur during malolactic
      fermentation and later on, could favour histamine production. SO(2) could prevent
      bacterial growth, but does not diminish the HDC enzyme activity. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Information on hdc expression and HDC activity can
      contribute to the prevention of histamine formation during wine production and
      storage.

PMID- 18713289
TI  - Evaluation of the fermentability of oat fractions obtained by debranning using
      lactic acid bacteria.
AB  - AIMS: The overall kinetics of the fermentation of four oat fractions obtained by
      debranning using three potentially probiotic lactic acid bacteria were
      investigated. The main objective was to study the suitability of these fractions
      as fermentation media for the growth and the metabolic production of bacteria
      isolated from human intestine. METHODS AND RESULTS: The cell growth, lactic acid
      production and substrate uptakes of the three lactobacilli was monitored for 30
      h. An unstructured mathematical model was used to describe and fit the
      experimental data. In the medium from fraction B (1-3% pearlings or beta-glucan
      rich fraction) all strains reached the highest cell populations, maximum growth
      rates and maximum lactic acid productions. This could be because of the high
      levels of total fibre and beta-glucan of this fraction. Limited growth and lactic
      acid formation was found in medium A (0-1% pearlings or bran-rich fraction).
      CONCLUSIONS: Medium B (1-3% pearling fraction) is the most suitable for
      fermentation and produces considerably higher probiotic cell concentrations.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Debranning technology could be used to
      separate fractions from cereal grains for the production of functional
      formulations with higher probiotic levels than the ones that were obtained with
      the whole grain.

PMID- 18713290
TI  - Comparison of Campylobacter jejuni genotypes from dairy cattle and human sources
      from the Matamata-Piako District of New Zealand.
AB  - AIMS: To identify the prevalence and types of Campylobacter jejuni carried by
      dairy cattle and the extent of overlap of these types with those causing disease
      in humans. METHODS AND RESULTS: Faecal samples from 410 dairy cattle were
      collected from 36 farms in the Matamata-Piako district in New Zealand.
      Campylobacter jejuni was isolated on all 36 farms, with a prevalence of 51% (95%
      CI 45-57) in dairy cattle and 65% (95% CI 58-72) in calves. Eighty-nine of these
      isolates were typed using Penner serotyping and pulsed field gel electrophoresis
      and were compared with 58 human C. jejuni isolates from people resident within
      this study area. CONCLUSIONS: Campylobacter jejuni were found in the faeces of
      over half of the dairy cows and calves examined. Twenty-one per cent of the
      bovine isolates and 43% of the human isolates formed indistinguishable clusters
      of at least one bovine and one human isolate. SIGNIFICANCE AND IMPACT OF THE
      STUDY: While a direct link between bovine isolates and human cases was not
      demonstrated, the finding of indistinguishable genotypes among C. jejuni isolates
      from bovine and human sources confirms that dairy cows and calves are a potential
      source of human campylobacteriosis. Barriers to separate bovine faecal material
      from the general public are therefore important public health measures.

PMID- 18713291
TI  - Effect of inoculation with putative plant growth-promoting rhizobacteria isolated
      from Pinus spp. on Pinus pinea growth, mycorrhization and rhizosphere microbial
      communities.
AB  - AIMS: In this study, 10 putative plant growth-promoting rhizobacteria (PGPR) were
      assayed for their ability to improve Pinus pinea growth and mycorrhization.
      METHODS AND RESULTS: After an inoculation assay, except for two, all strains
      stimulated plant growth. All bacteria altered rhizosphere microbial communities
      as revealed by phospholipid fatty acid analysis; associating plant growth
      promotion with a decrease in biological diversity. Three strains were tested for
      their ability to enhance pine mycorrhization with wild fungi species. Only strain
      BB1 increased the total number of mycorrhizal root tips. Mycorrhizas present in
      the roots of each treatment were identified by ribosomal RNA sequencing and
      denaturing gradient gel electrophoresis analysis, detecting specificity between
      mycorrhizal species colonizing the roots and the inoculated PGPR. CONCLUSIONS: In
      conclusion, BB1 appears to be a good candidate to be developed into a
      biofertilizer directed to enhance pine growth and mycorrhization, which should
      result in a better establishment rate for plants used in reforestation.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows the potential of PGPR to
      improve fitness of forest tree specie. Moreover, the specificity between the
      bacteria inoculated and the mycorrhiza that the plant selects involve a potential
      biotechnological use in production of value-added fungi.

PMID- 18713292
TI  - Degradation of forage chicory by ruminal fibrolytic bacteria.
AB  - AIMS: Determine the susceptibility of forage chicory (Cichorium intybus L.) to
      degradation by ruminal fibrolytic bacteria and measure the effects on cell-wall
      pectic polysaccharides. METHODS AND RESULTS: Large segments of fresh forage
      chicory were degraded in vitro by Lachnospira multiparus and Fibrobacter
      succinogenes, but not by Ruminococcus flavefaciens or Butyrivibrio hungatei. Cell
      wall pectins were degraded extensively (95%) and rapidly by L. multiparus with a
      simultaneous release of uronic acids and the pectin-derived neutral
      monosaccharides arabinose, galactose and rhamnose. Fibrobacter succinogenes also
      degraded cell-wall pectins extensively, but at a slower rate than L. multiparus.
      Immunofluorescence microscopy using monoclonal antibodies revealed that, after
      incubation, homogalacturonans with both low and high degrees of methyl
      esterification were almost completely lost from walls of all cell types and from
      the middle lamella between cells. CONCLUSIONS: Only two of the four ruminal
      bacteria with pectinolytic activity degraded fresh chicory leaves, and each
      showed a different pattern of pectin breakdown. Degradation was greatest for F.
      succinogenes which also had cellulolytic activity. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The finding of extensive removal of pectic polysaccharides from the middle
      lamella and the consequent decrease in particle size may explain the decreased
      rumination and the increased intake observed in ruminants grazing forage chicory.

PMID- 18713293
TI  - Growth of pure cultures of Verocytotoxin-producing Escherichia coli in a range of
      enrichment media.
AB  - AIMS: This study compared the growth of different strains of Verocytotoxin
      producing Escherichia coli (VTEC) in a range of selective enrichment media.
      METHODS AND RESULTS: Turbidometric and impedance methods were used to determine
      the growth of VTEC in pure culture in different enrichment media. Ten strains
      failed to grow in buffered peptone water + vancomycin, cefsulodin, cefixime at 42
      degrees C and some failed to grow, or grew poorly in E. coli (EC) medium
      supplemented with 20 mg l(-1) novobiocin and modified EC supplemented with 20 mg
      l(-1) novobiocin at 37 degrees C and 42 degrees C. Individual VTEC strains were
      sensitive to the selective agents in some media. Statistical analysis of the
      conductance detection times of 10 strains showed no overall effect of temperature
      alone (P = 0.66) but there were significant (P < 0.001) effects as a result of
      the combination of medium and temperature and these two factors were influenced
      by strain. CONCLUSIONS: Growth of VTEC during enrichment is dependent on
      different factors alone or in combination. These include medium type, presence of
      certain selective agents or antibiotics, incubation temperature and the initial
      population of VTEC. Sensitivity to these conditions can be strain related.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlighted differences in the
      ability of some enrichment media to support the growth of VTEC, making them
      unsuitable for the isolation of VTEC, especially low numbers of non-O157 strains.

PMID- 18713294
TI  - Radiofrequency ablation of hepatic tumors: lessons learned from 3000 procedures.
AB  - Radiofrequency ablation has been accepted as the most popular local ablative
      therapy for unresectable malignant hepatic tumors. For 9 years from April 1999,
      we performed 3000 radiofrequency ablation procedures for hepatic tumors in our
      institution. Our results on the safety (mortality, 0.15%/patient) and therapeutic
      efficacy (5-year survival rate, 58%) are similar to those of previous studies
      reported, supporting the growing evidence of a clear survival benefit, excellent
      results for local tumor control and improved quality of life. The most important
      lesson learned from our 3000 procedures is that the best planning, safe ablation
      and complete ablation are key factors for patient outcome. Furthermore,
      multimodality treatment is the best strategy for recurrent hepatocellular
      carcinoma encountered after any kind of first-line treatment.

PMID- 18713295
TI  - Long-term results of balloon-occluded retrograde transvenous obliteration for
      gastric variceal bleeding and risky gastric varices: a 10-year experience.
AB  - BACKGROUND AND AIM: Balloon-occluded retrograde transvenous obliteration (B-RTO)
      is a new alternative treatment for gastric varices (GVx), but the long-term
      efficacy is not known. We investigated the long-term effects of B-RTO on
      rebleeding, prevention of first bleeding, mortality and occurrence of risky
      esophageal varices (EVx). METHODS: B-RTO was performed in 68 cirrhotic patients
      with GVx. Twenty patients had recent bleeding, transiently treated by endoscopic
      Histoacryl injection or balloon tamponade. Forty-eight patients had varices
      likely to bleed, but no bleeding. After B-RTO, the recurrent bleeding, occurrence
      of EVx and mortality over the long-term were evaluated. RESULTS: B-RTO was
      successfully performed in 63 of 68 patients (92.6%). Varices eradication was
      confirmed by endoscopy in 61 of 63 patients (96.6%). During follow up, GVx
      bleeding occurred in two patients (3.2%). The 8-year cumulative rebleeding rates
      of patients with bleeding and risky GVx were 14% and 0%, respectively. Risky EVx
      occurred in 10 patients (17%) and the cumulative occurrence rate was 22% in 8
      years. The cumulative occurrence rate of risky EVx was higher in GVx with EVx
      (GOV2-GVx) compared to GVx without EVx (IGV1, P < 0.05). No ectopic variceal
      bleeding occurred. No patients died from variceal bleeding. Hepatocellular
      carcinoma was the only significant prognostic factor (P < 0.05). CONCLUSION: B
      RTO is beneficial over the long-term, despite worsening EVx in some patients,
      because of excellent treatment efficacy and improved mortality. We believe that B
      RTO can become a first-choice radical treatment following hemostasis for gastric
      variceal bleeding and prophylactic treatment for risky GVx.

PMID- 18713296
TI  - Expression of adiponectin and its receptors in livers of morbidly obese patients
      with non-alcoholic fatty liver disease.
AB  - BACKGROUND AND AIM: Obesity is one of the risk factors for non-alcoholic fatty
      liver disease (NAFLD) and a common disease that comprises simple steatosis and
      non-alcoholic steatohepatitis (NASH), and can eventually lead to liver cirrhosis.
      Adiponectin is an adipocyte-derived protein that has anti-obesity, antidiabetic
      and anti-inflammatory properties, and is considered to possess a hepatoprotective
      function. Its role in the development and progression of NAFLD in morbidly obese
      patients is unknown. In this study, we examined the expression levels of
      adiponectin and its receptors in liver biopsies of morbidly obese patients and
      then determined whether there was an association with the disease severity.
      METHODS: Liver biopsies from 30 morbidly obese patients (18 NASH vs 12 steatosis)
      were analyzed. The needle core biopsies were subjected to routine histological
      examination and stained immunohistochemically for adiponectin, adiponectin
      receptor I (adipoRI) and receptor II (adipoRII). RESULTS: The two groups were
      comparable with respect to body mass index, age and gender distribution. The
      expression of adiponectin decreased in liver biopsies with NASH as compared to
      those with simple steatosis (1.61 +/- 0.70 vs 2.25 +/- 0.75, P = 0.028).
      Spearman's rank correlation coefficient analysis showed that the staining
      intensity of adiponectin negatively correlated with the grade of inflammation (r
      = -0.368, P = 0.045) and stage of fibrosis (r = -0.380, P = 0.038). There was no
      significant difference in expression of adipoRI and adipoRII between the two
      groups. CONCLUSION: These findings indicate that decreased liver adiponectin
      expression may play a role in the development and progression of NAFLD, from
      simple steatosis to NASH, in morbidly obese patients.

PMID- 18713297
TI  - Can computed tomography with coronal reconstruction improve the diagnosis of
      choledocholithiasis?
AB  - BACKGROUND AND AIM: Many technical developments of computed tomography (CT) made
      in recent years have improved imaging quality. However, the diagnostic efficacy
      of CT with coronal reconstruction for choledocholithiasis remains uncertain. This
      study aimed to investigate if CT with coronal reconstruction can aid in the
      diagnosis of choledocholithiasis. METHODS: Two hundred and sixty-six patients
      with clinically suspected choledocholithiasis undergoing abdominal CT before
      endoscopic retrograde cholangiopancreatography were recruited. Among them, 163
      patients confirmed with choledocholithiasis were divided into three groups: group
      1, 92 patients undergoing CT using 5-mm thick sections with coronal
      reconstruction; group 2, 32 patients undergoing CT using 5-mm thick sections
      without coronal reconstruction; and group 3, 39 patients undergoing CT using 7-mm
      thick sections without coronal reconstruction. The diagnostic rate of CT for
      choledocholithiasis, the stone size and biochemical data among the three groups
      were analyzed. RESULTS: The sensitivity and specificity of CT in diagnosing
      choledocholithiasis were 77.3% and 72.8%. There was no significant difference of
      CT diagnostic rate among the three groups (75.0%, 81.2% and 79.5%, respectively).
      The diameter of common bile duct (CBD), size of CBD stones and white cell count
      showed significant differences between CT true-positive and false-negative cases
      in group 1 patients. The CT diagnostic rate was significantly lower in patients
      with choledocholithiasis of less than 5 mm than in patients with
      choledocholithiasis of 5 mm or more (56.5% vs 81.2%). CONCLUSION: The coronal
      reconstruction of CT imaging did not increase its diagnostic efficacy on
      choledocholithiasis. The stone size affects the diagnostic rate of abdominal CT
      for detecting choledocholithiasis.

PMID- 18713298
TI  - Role of intestinal metaplasia subtyping in the risk of gastric cancer in Korea.
AB  - BACKGROUND AND AIM: Gastric cancer is believed to develop by a multistage
      process. Intestinal metaplasia (IM) is regarded as a premalignant condition; it
      is classified into subtypes I, II and III. The aim of this study was to evaluate
      whether the subtypes of IM were associated with progression to gastric cancer.
      METHODS: The study cohort consisted of 861 subjects, categorized as controls,
      gastric ulcers, dysplasia and cancer. The IM was scored histologically using the
      Sydney classification for the antrum and the body of the stomach. The biopsies
      were stained with high iron diamine and alcian blue (pH 2.5) (HID-AB2.5), and the
      IM was subtyped as I, II or III. RESULTS: The proportion of IM subtypes I, II and
      III were 14.5%, 47.2% and 38.3% in the antrum, and 28.1%, 57.8% and 14.1% in the
      body of the stomach, respectively. These distributions did not show significant
      differences depending on disease or Helicobacter pylori positivity. In cases that
      were H. pylori-positive, the prevalence of IM subtype II in the cancer and
      dysplasia groups was higher than in the control group in the body of the stomach
      (P < 0.05). The proportion of IM subtype III in the antrum increased in
      proportion with age (P = 0.036). CONCLUSIONS: IM subtyping was not found to play
      a major role in the prediction of gastric cancer development in Korea. IM subtype
      III was associated with aging, and IM subtype II appeared to be related to
      gastric carcinogenesis in the presence of H. pylori infection.

PMID- 18713299
TI  - Endoscopic fibrin sealing of gastrocutaneous fistulas after sleeve gastrectomy
      and biliopancreatic diversion with duodenal switch.
AB  - BACKGROUND AND AIM: Gastrocutaneous fistulas (GCF) are uncommon complications
      accounting for 0.5-3.9% of gastric operations. When their management is not
      effective, the mortality rate is high. This study reports the conservative
      treatment of GCF in morbidly obese patients who underwent biliopancreatic
      diversion with duodenal switch. METHODS: Ninety-six morbidly obese patients were
      treated in our department with biliopancreatic diversion with duodenal switch
      (Marceau technique) and, in six of them, a high-output GCF developed. A general
      protocol was applied to all patients presenting a GCF. Everyone was treated by
      total parenteral nutrition (TPN) and somatostatin for at least 7 days after the
      appearance of the leak. If the leak continued, then fibrin glue was used as a
      tissue adhesive. Endoscopic application of the sealant was accomplished under
      direct vision via a double-lumen catheter passed through a forward-viewing
      gastroscope. RESULTS: All patients were treated successfully with conservative
      treatment (either solely with TPN and somatostatin, or with endoscopic fibrin
      sealing sessions). No evidence of fistula was observed at gastroscopy 3 and 24
      months after therapy. CONCLUSION: The conservative treatment of GCF following
      biliopancreatic diversion with duodenal switch is highly effective. All patients
      should enter a protocol that includes TPN and somatostatin. When the GCF persist,
      endoscopic sealing glue should be considered before operation because it is
      simple, safe, effective and, in some cases, life-saving. Therefore, conservative
      treatment should be employed as a therapeutic option in GCF developing after
      bariatric surgery.

PMID- 18713300
TI  - Polymorphism of human leptin receptor gene is associated with type 2 diabetic
      patients complicated with non-alcoholic fatty liver disease in China.
AB  - BACKGROUND AND AIM: To investigate the relationship between human leptin receptor
      (LEPR) gene G3057A polymorphism and type 2 diabetes mellitus (T2DM) patients
      complicated with or without non-alcoholic fatty liver disease (NAFLD). METHODS:
      Two hundred and sixteen cases of newly diagnosed T2DM patients (104 cases
      complicated with NAFLD) and 108 cases of normal glucose tolerances (NGT) were
      recruited. Hemi-nested polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP) and PCR-direct sequence analysis were conducted to detect
      the polymorphism of LEPR G3057A variation. Plasma leptin levels were measured by
      enzyme-linked immunosorbent assay kit. Plasma lipid and glucose metabolic
      parameters were measured routinely. Liver ultrasound was carried out for all
      subjects. RESULTS: T2DM patients complicated with NAFLD had higher plasma
      insulin, leptin, triglycerides (TG) and low-density lipoprotein cholesterol (LDL
      C) levels than those without NAFLD and NGT subjects. The variant frequency at
      nucleotide 3057 G-->A transversion was 76.0% in type 2 diabetic patients
      complicated with NAFLD, which was also significantly higher than those without
      NAFLD (62.1%) and NGT cases (53.2%). There was also significant difference in
      genotype distribution between the three groups (chi(2) = 14.63, P < 0.01).
      CONCLUSION: The polymorphism of LEPR gene 3057 probably contributes to the onset
      of NAFLD by regulating lipid metabolism and affecting insulin sensitivity.

PMID- 18713301
TI  - Diabetes mellitus worsens the recurrence rate after potentially curative therapy
      in patients with hepatocellular carcinoma associated with nonviral hepatitis.
AB  - BACKGROUND AND AIM: The aim of this retrospective study was to examine the
      relationship between diabetes mellitus and recurrence of hepatocellular carcinoma
      after potentially curative therapy for hepatocellular carcinoma with nonviral
      hepatitis. METHODS: We studied 40 consecutive hepatocellular carcinoma patients
      who were diagnosed between 1980 and 2006 with hepatocellular carcinoma associated
      with non-B, non-C hepatitis, and later underwent surgical resection or
      radiofrequency ablation. RESULTS: Twenty-two out of the 40 patients developed
      hepatocellular carcinoma recurrence within a median of 3.7 years. In the 18
      patients with diabetes mellitus, the cumulative rates of hepatocellular carcinoma
      recurrence were 22.2% at the first year, 55.6% at the second year, 61.1% at the
      third year, 61.1% at the fourth year, and 80.6% at the fifth year. The cumulative
      rates of hepatocellular carcinoma recurrence in 22 nondiabetic patients were
      24.6% at the first year, 24.6% at the second year, 31.5% at the third year, 31.5%
      at the fourth year, and 31.5% at the fifth year. The hepatocellular carcinoma
      recurrence rate was significantly higher in diabetic patients than in
      nondiabetics (P = 0.026). The multivariate Cox proportional model identified old
      age and diabetes as the only significant predictors for recurrence. The hazard
      ratio of hepatocellular carcinoma recurrence in diabetic patients was 4.61 (P =
      0.007). There was no significant difference in overall survival rate between
      diabetic and nondiabetic patients (P = 0.392). CONCLUSION: Diabetes is a
      significant predictor of tumor recurrence after potentially curative therapy for
      hepatocellular carcinoma in patients with nonviral hepatitis.

PMID- 18713302
TI  - Undetermined focal liver lesions on gray-scale ultrasound in patients with fatty
      liver: characterization with contrast-enhanced ultrasound.
AB  - BACKGROUND AND AIM: The purpose of this study was to assess the clinical value
      and potential impact of contrast-enhanced ultrasound (CEUS) in the
      characterization of undetermined focal liver lesions (FLLs) in patients with
      fatty liver. METHODS: Fifty-two patients (34 men, 18 women) with fatty liver with
      67 FLLs (size range, 1-8.6 cm; mean, 4.1 +/- 3.1 cm) undetermined at baseline
      ultrasound (US) underwent contrast-enhanced US. CEUS examinations were analyzed
      by two experienced sonologists blinded to the final diagnosis. Readers evaluated
      by consensus the baseline echogenicity, the dynamic enhancement pattern in
      comparison with peripheral liver parenchyma. The final diagnosis was based on
      consensus interpreting of all examinations by another two expert observers with
      access to histological data. The characterization accuracy, sensitivity, and
      specificity of CEUS in characterizing the lesion as benign or malignant, and as
      the correct pathologic type, were analyzed. RESULTS: After CEUS, two hemangiomas,
      three inflammatory pseudotumors, and one hepatocellular carcinoma were
      misdiagnosed. The overall characterization accuracy, sensitivity and specificity
      of CEUS were 91% (61/67), 91.7% (11/12), and 90.9% (50/55), respectively. Forty
      three benign lesions were diagnosed as the correct pathologic type. The portal
      venous phase and late phase were important in the characterization of the
      lesions. The characterization accuracy had no relationship with the size of FLLs.
      CONCLUSION: CEUS can improve the characterization of undetermined FLLs arising
      from fatty liver.

PMID- 18713303
TI  - Imaging of liver disease: comparison between quadruple-phase multidetector
      computed tomography and magnetic resonance imaging.
AB  - BACKGROUND AND AIM: To compare quadruple-phase multidetector computed tomography
      (MDCT) and magnetic resonance imaging (MRI) for the assessment of focal and
      diffuse liver disease. METHODS: Quadruple-phase contrast-enhanced MDCT and MRI of
      37 consecutive patients were retrospectively reviewed by two readers (R1 and R2).
      In patients with focal liver lesions, the gold standard was histopathology (n =
      17) and/or long-term (>6 months) follow-up imaging (n = 27) or transarterial
      chemoembolization (n = 1). Diffuse liver disease was confirmed by histopathology
      in all patients, when present. RESULTS: Both readers identified 60 focal liver
      lesions on MDCT and 56 focal liver lesions on MRI. Gold standard diagnoses
      revealed 48 focal liver lesions in 25 patients. Diagnosis of malignant liver
      lesions revealed a sensitivity of 88% (R1) and 91% (R2) for MRI; 63% (R1) and 66%
      (R2) for MDCT; and a specificity of 75% (R1) and 79% (R2) for MRI; 50% (R1) and
      64% (R2) for MDCT. MRI was superior to MDCT for the diagnosis of malignant focal
      liver lesions, when the mean areas under the alternative free-response receiver
      operating characteristic curves (A(Z)) were compared (MRI = 0.93 vs CT = 0.69),
      (P < 0.00001). Thirty-three patients had histopathologically confirmed diffuse
      liver disease. Overall diagnosis of diffuse liver disease revealed a sensitivity
      of 88% (R1) and 92% (R2) for MRI; 75% (R1) and 74% (R2) for MDCT; and a
      specificity of 100% for both modalities by both readers. CONCLUSIONS: MRI is
      superior for the assessment of malignant focal liver lesions and diffuse liver
      disease compared to quadruple-phase MDCT, and can be considered as primary
      diagnostic imaging modality for liver imaging.

PMID- 18713304
TI  - Correlation of hepatocyte expression of hepatitis B viral antigens with
      histological activity and viral titer in chronic hepatitis B virus infection: an
      immunohistochemical study.
AB  - BACKGROUND AND AIM: The localization of hepatitis B virus (HBV) core antigen to
      the nucleus or cytoplasm of hepatocytes has biological implications for viral
      packaging and persistence. This study examined the relationship between the
      localization of hepatitis B virus antigens, histological activity, and viral
      titer in patients with chronic HBV infection. METHODS: Liver biopsies from 110
      patients with chronic HBV infection were studied. Ishak's scoring system was used
      for the histological analysis. The localization of hepatitis B surface antigen
      (HBsAg) and hepatitis B core antigen (HBcAg) and the percentage of hepatocytes
      stained positive by immunohistochemistry were correlated with viral titer,
      histological activity, and fibrosis indices using Spearman rank correlation.
      RESULTS: In 88 hepatitis B e-antigen (HBeAg)-positive individuals, the nuclear
      localization of HBcAg correlated significantly with DNA titer (r = 0.435, P =
      0.001) and negatively with fibrosis (r = -0.297, P = 0.005). The cytoplasmic
      localization correlated significantly with histological activity (r = 0.211, P =
      0.049). In 22 HBeAg-negative individuals, the nuclear localization of HBcAg
      correlated significantly with histological activity (r = 0.625, P = 0.002), DNA
      titer (r = 0.651, P = 0.009), and fibrosis (r = 0.447, P = 0.042). The
      cytoplasmic localization correlated significantly with DNA titer (r = 0.524, P =
      0.045) and fibrosis (r = 0.528, P = 0.012). There was no correlation of HBsAg
      expression with DNA titer, histological activity index, or fibrosis in both
      groups. HBeAg-positive patients presented at a younger age. CONCLUSION: In HBeAg
      positive individuals, nuclear core antigen correlated with DNA titer, and
      cytoplasmic localization with histological activity, whereas in HBeAg-negative
      individuals, nuclear localization correlated with DNA titer, histological
      activity, and fibrosis, and cytoplasmic localization correlated with DNA titer
      and fibrosis, but not with histological activity. These observations suggest
      biological differences between HBeAg-positive and -negative disease.

PMID- 18713305
TI  - Outcome of self-expandable metallic stents in low-grade versus advanced hilar
      obstruction.
AB  - BACKGROUND: Self-expandable metallic stents (SEMS) are known to provide a longer
      patency time than plastic stents for malignant biliary obstructions including
      hilar obstruction. However, studies that focus on the efficacy of SEMS in low
      grade and advanced hilar obstructions are still scanty. METHODS: Ninety four
      patients with malignant hilar obstructions were enrolled (six were later
      excluded). Patients were divided into two groups according to their Bismuth
      levels. Group A were patients with Bismuth I (n = 53). Group B were patients with
      Bismuth II, III and IV (n = 35). Technical success, complications, jaundice
      resolution, stent patency time, and patients' survival were analyzed. RESULTS:
      Our intention-to-treat analysis showed that group A had a significant lower rate
      of post-endoscopic retrograde cholangiopancreatography (ERCP) cholangitis than
      group B; 16.1% versus 44.7%, (P < 0.01). Four patients from group B still had
      persistent jaundice. Our per protocol analysis demonstrated that median stent
      patency time in groups A and B were not statistically different (74 vs 60 days).
      Median survival time in groups A and B were also not statistically different (90
      vs 75 days). In both groups, those without liver metastasis had significantly
      better patency and survival time than those with liver metastasis (P = 0.010 and
      0.027, respectively). CONCLUSIONS: In patients with hilar obstruction, liver
      metastasis is one of the main factors that determine survival of the patient.
      Patency times of SEMS in both low-grade and advanced obstructions are comparable.
      However, in the advanced group, there is a significant risk of post-ERCP
      cholangitis.

PMID- 18713306
TI  - Age and gender affect likely manometric diagnosis: Audit of a tertiary referral
      hospital clinical esophageal manometry service.
AB  - BACKGROUND AND AIM: Awareness of patient demographics, common diagnoses and
      associations between these may improve the use and interpretation of manometric
      investigations. The aim of the present study therefore was to determine whether
      age and/or gender affect manometric diagnosis in a clinical motility service.
      METHODS: An audit of all 452 clinical manometry reports issued from December 2003
      to July 2005 with respect to age, gender and diagnosis was carried out. Patients
      were divided by age (17-24 years n = 14, 25-44 years n = 87, 45-64 years n = 216
      and >or=65 years n = 135), and gender and data compared using contingency tables.
      RESULTS: Women were more commonly referred overall (59%) and in each age bracket
      except <25 years (64% male). Men were more likely to have 'hypotensive' motor
      problems P = 0.01. With aging, normal motor function became less common (P =
      0.013), with non-specific motor disorder, ineffective/hypotensive peristalsis and
      'achalasia-like' conditions each more common (individual P = NS). Increasing age
      showed a trend for increased spastic motor disorders (P = 0.06). Gender did not,
      however, influence whether motility was abnormal (P = 0.5), spastic (P = 0.7) or
      whether a non-specific motor disorder was present (P = 0.1). In the total cohort,
      the principal manometric diagnoses were: non-specific motor disorder 33%, normal
      motility 29%, low basal lower esophageal sphincter pressure 18%,
      hypotensive/ineffective peristalsis 10%, achalasia/achalasia-like 6%, diffuse
      esophageal spasm 3% and other 1%. CONCLUSIONS: Aging leads to increasing
      esophageal motor abnormalities. Men and women have similar rates of dysfunction,
      although 'low-pressure problems' were more common in men.

PMID- 18713307
TI  - Comparisons between a mixing ability test and masticatory performance tests using
      a brittle or an elastic test food.
AB  - A variety of chewing tests and test items have been utilized to evaluate
      masticatory function. The purpose of this study was to compare a mixing ability
      test with masticatory performance tests using peanuts or gummy jelly as test
      foods. Thirty-two completely dentate subjects (Dentate group, mean age: 25.1
      years) and 40 removable partial denture wearers (RPD group, mean age: 65.5 years)
      participated in this study. The subjects were asked to chew a two-coloured
      paraffin wax cube as a test item for 10 strokes. Mixing Ability Index (MAI) was
      determined from the colour mixture and shape of the chewed cube. Subjects were
      asked to chew 3 g portions of peanuts and a piece of gummy jelly for 20 strokes,
      respectively. Median particle size of chewed peanuts was determined using a
      multiple-sieving method. Concentration of dissolved glucose from the surface of
      the chewed gummy jelly was measured using a blood glucose meter. Pearson's
      correlation coefficient was used to test the relationships between the MAI,
      median particle size and the concentration of dissolved glucose. Mixing Ability
      Index was significantly related to median particle size (Dentate group: r = 
      0.56, P < 0.001, RPD group: r = -0.70, P < 0.001), but not significantly related
      to glucose concentration (Dentate group: r = 0.12, RPD group: r = 0.21, P >
      0.05). It seems that ability of mixing the bolus is more strongly related to the
      ability of comminuting brittle food than elastic food.

PMID- 18713308
TI  - Proclination of lower incisors: a design to maximize food penetration and
      minimize torque.
AB  - Human upper and lower incisors are both tilted forward in the sagittal plane.
      Previous theoretical and in vitro studies have investigated how proclination may
      help the teeth either to penetrate or to fracture food more effectively or both.
      We study the proclination of lower incisors in relation to efficiency and to the
      protection it may offer from potentially damaging torque forces. Lateral
      cephalographs from 57 normal human subjects were traced. In one study, a line was
      drawn joining the centre of the condyle to the tip of the lower incisor. The
      results showed the lower incisor is oriented so that it is closely parallel to
      the arc of a circle centred at the condyle. In another study, lines were drawn
      joining the tips of upper and lower incisors at different openings. Each line
      showed the direction of the force that must be used to bite an object held
      between the tips of the incisor teeth. Its direction was compared with the
      direction of the long axis of the lower incisor when the mandible was graphically
      rotated open. The results showed the long axis of the lower incisor is closest to
      the direction of the bite force at 12 degrees and 15 degrees of jaw openings
      (roughly 20-25 mm incisal separation). This is the opening where the maximum
      incisal force is normally produced. The findings suggest that to reduce the
      torque, lower incisors implanted or relocated during orthodontic treatment should
      be oriented parallel to the closing arc.

PMID- 18713309
TI  - Influence of palatal surface shape of dentures on food perception.
AB  - The purpose of this study was to clarify the influence of the palatal surface
      shape of dentures on food perception. Eighteen healthy dentulous subjects (mean
      age, 24 years) were investigated. Four types of experimental plate were used: (i)
      a tailor-made plate, (ii) an average-model plate, (iii) a smooth plate, and (iv)
      a wrinkle plate. Test foods consisted of Bavarian cream cubes containing one to
      three mustard seeds and six raw carrot pieces of different shapes. Bavarian cream
      cubes with three seeds were used for analysis. Other foods were used as dummy
      foods. Subjects were required to wear experimental plates and press test foods
      placed on the anterior area of the tongue against the experimental plates. We
      measured time required to perceive number of spherical bodies, rate of correct
      answers, and level of perception with each type of experimental plate using a 100
      mm visual analogue scale. The results showed a significant difference in response
      time between the average-model plate and the other experimental plates, with
      response time longest for the average-model plate. On the other hand, no
      significant differences in rate of correct answers regarding number of spherical
      bodies or level of perception were found among the experimental plates. When
      incisive papilla, palatine suture and palatal rugae based on the standard
      Japanese shape were replicated on the palatal surface of the plates, the time
      required for food perception during ingestion was prolonged in comparison to
      plates with other palatal surface shapes.

PMID- 18713310
TI  - Lack of association between PSA-NCAM expression and migration in the rostral
      migratory stream of a Huntington's disease transgenic mouse model.
AB  - Huntington's disease is a neurodegenerative autosomal disorder characterized by
      selective loss of striatal and cortical neurons. The mammalian brain
      subventricular zone contains a population of neural precursors involved in
      postnatal neurogenesis. These newly generated cells migrate from the
      subventricular zone along the rostral migratory stream and differentiate into
      mature olfactory bulb neurons throughout adulthood. The establishment of this
      pathway depends upon a variety of molecules, including polysialylated neural cell
      adhesion molecule (PSA-NCAM). We used a murine model of Huntington's disease, the
      R6/2 transgenic mouse, and in vivo bromodeoxyuridine administration to label
      cells undergoing proliferation and to follow their migration along the rostral
      migratory stream. Bromodeoxyuridine labeling did not show any significant
      increase in proliferation of progenitor cells in symptomatic R6/2 mice, but
      migration of neuroblasts along the rostral migratory stream was significantly
      diminished. The decrease in neuroblast migration was not due to an alteration in
      the expression of PSA-NCAM along the rostral migratory stream since
      immunohistochemical analysis showed no significant differences between R6/2 and
      wild type mice. In addition, we used Fluoro-Jade C to evaluate apoptosis and
      demonstrated that the number of apoptotic cells in the rostral migratory stream
      is similar in affected and wild type animals, suggesting that cell death is not
      responsible for the differences observed in neuroblast migration. We conclude
      that in R6/2 mice, progenitor cells have an impaired migration in their route to
      the olfactory bulb, with accumulation of cells in the caudal rostral migratory
      stream that does not result from changes in PSA-NCAM expression and/or cell
      death.

PMID- 18713311
TI  - Meningeal alveolar soft part sarcoma confirmed by characteristic ASPCR1-TFE3
      fusion.
AB  - Sarcoma metastatic to the brain is uncommon and rarely occurs as the initial
      manifestation of tumor. Alveolar soft part sarcoma (ASPS) is a rare but well
      studied subtype of sarcoma. A 39-year-old man presented with seizures due to a
      left temporal meningeal-enhancing lesion with striking brain edema on MRI. The
      patient underwent neurosurgical resection for suspected meningioma. Histology
      showed large tumor cells clustering and forming small nests, in places with
      pseudoalveolar pattern. Diastase-resistant periodic acid-Schiff revealed very
      rare granular and rod-like cytoplasmic inclusions. Immunohistochemistry showed
      convincing positivity only with vimentin and smooth muscle actin. The
      histological features were strongly suggestive of ASPS. At the molecular level RT
      PCR and sequencing analysis demonstrated ASPCR1-TFE3 fusion confirming the
      histological diagnosis of ASPS. There was no evidence of primary extracranial
      tumor by physical examination and on chest and abdominal CT scan 11 months after
      presentation. ASPS typically arise from the soft tissues of the extremities and
      develop multiple metastatic deposits usually with a long clinical course. This
      case may represent primary meningeal ASPS although metastatic deposit from an
      undiscovered primary site cannot be entirely excluded.

PMID- 18713312
TI  - Gastric hypersensitivity induced by oesophageal acid infusion in healthy
      volunteers.
AB  - Distal oesophageal acid exposure has been shown to increase visceral sensitivity
      of the proximal oesophagus via central sensitization. Here we evaluated whether
      acidification of the distal oesophagus also affects the sensorimotor function of
      the proximal stomach. A gastric barostat study combined with a 30-min acid (HCl
      0.15 mol L(-1)) or saline infusion in the distal oesophagus was performed in 18
      healthy volunteers. Gastric and cutaneous sensitivity was assessed before and up
      to 2 h after the start of infusion. Directly after acid infusion, but not after
      saline, the threshold for discomfort decreased (-6.4 +/- 1.7 vs 0.4 +/- 0.4 mmHg;
      P = 0.028) and distension-induced symptoms increased significantly compared with
      the baseline (122 +/- 49% vs -3 +/- 9%). Cutaneous sensitivity remained
      unaffected by acid infusion. In contrast, when the infused liquid was aspirated 3
      cm more distally, at the level of the lower oesophageal sphincter, the effect of
      acid infusion on gastric sensitivity was abolished and the increase in distension
      induced symptoms was reduced (61 +/- 24%). Distal oesophageal acid infusion
      induces visceral hypersensitivity without affecting somatic sensitivity arguing
      against a similar mechanism of central sensitization as observed in non-cardiac
      chest pain. As reduction of the acid load to the stomach prevented this effect,
      our findings indicate that either gastric and/or duodenal acidification is
      involved. It should be emphasized though that aspiration from distal oesophagus
      may have attenuated the effect by reducing the acid-exposed area or by reducing
      the contact time.

PMID- 18713313
TI  - Barley Rom1 antagonizes Rar1 function in Magnaporthe oryzae-infected leaves by
      enhancing epidermal and diminishing mesophyll defence.
AB  - * Barley (Hordeum vulgare) is a host for Blumeria graminis f. sp. hordei (Bgh),
      which causes powdery mildew, and for the rice blast pathogen Magnaporthe oryzae.
      It has previously been shown that Rar1, initially identified in a mutational
      screen as being required for Mla12-specified Bgh-resistance, also controlled
      pathogenic growth of M. oryzae in barley. Here, we tested whether the rom1
      mutation (restoration of Mla12-specified resistance), which restored resistance
      against Bgh in a susceptible rar1-2 genetic background, also influences the
      interaction between barley and M. oryzae. * Disease severity after infection with
      M. oryzae was analysed on rar1-2 mutants and rar1-2 rom1 double mutants.
      Microscopy and northern analysis were used to gain insight into cellular and
      molecular events. * On rar1-2 rom1 double mutant plants, the number of M. oryzae
      disease lesions was increased in comparison to the wild-type and the rar1-2
      mutant which correlated with augmented epidermal penetration. However, a decrease
      in the lesion diameter, apparently conditioned in the mesophyll, was also
      observed. * These results highlight the impact of Rom1 in basal defence of barley
      against different pathogens. Importantly, a tissue-specific function for Rom1
      with contrasting effects on epidermal and mesophyll defence was demonstrated.

PMID- 18713314
TI  - Evolutionary history of the ancient cutinase family in five filamentous
      Ascomycetes reveals differential gene duplications and losses and in Magnaporthe
      grisea shows evidence of sub- and neo-functionalization.
AB  - * The cuticle is the first barrier for fungi that parasitize plants
      systematically or opportunistically. Here, the evolutionary history is reported
      of the multimembered cutinase families of the plant pathogenic Ascomycetes
      Magnaporthe grisea, Fusarium graminearum and Botrytis cinerea and the
      saprotrophic Ascomycetes Aspergillus nidulans and Neurospora crassa. * Molecular
      taxonomy of all fungal cutinases demonstrates a clear division into two ancient
      subfamilies. No evidence was found for lateral gene transfer from prokaryotes.
      The cutinases in the five Ascomycetes show significant copy number variation,
      they form six clades and their extreme sequence diversity is highlighted by the
      lack of consensus intron. The average ratio of gene duplication to loss is 2 : 3,
      with the exception of M. grisea and N. crassa, which exhibit extreme family
      expansion and contraction, respectively. * Detailed transcript profiling in vivo,
      categorizes the M. grisea cutinases into four regulatory patterns. Symmetric or
      asymmetric expression profiles of phylogenetically related cutinase genes suggest
      subfunctionalization and neofunctionalization, respectively. * The cutinase
      family-size per fungal species is discussed in relation to genome characteristics
      and lifestyle. The ancestry of the cutinase gene family, together with the
      expression divergence of its individual members provides a first insight into the
      drivers for niche differentiation in fungi.

PMID- 18713315
TI  - Susceptibility to Fas and tumor necrosis factor-alpha receptor mediated apoptosis
      of anti-CD3/anti-CD28-activated umbilical cord blood T cells.
AB  - Decreased severity of graft-versus-host disease after mismatched umbilical cord
      blood (UCB) transplantation may be attributed in part to the increased propensity
      to apoptosis of UCB T cells following activation. Interleukin (IL)-15, a
      pleiotropic cytokine that is essential for T-cell proliferation and survival, may
      serve as promising immunomodulative therapy post-CB transplantation for its anti
      apoptotic effect. This study aimed to determine the kinetics of Fas or tumor
      necrosis factor-alpha receptor (TNFR) mediated caspase-3 expression and apoptosis
      of anti-CD3/anti-CD28 activated UCB T cells in the influence of IL-15. Activated
      caspase-3 expression was analyzed by Western blotting and the percentage of
      apoptotic cells was determined by annexin-V/propidium iodide (PI) flow cytometric
      staining. Significant expression of Fas and TNFR2 was detected on anti-CD3/anti
      CD28 pre-activated UCB T cells. These cells were susceptible to anti-Fas but not
      TNF-alpha-induced apoptosis. Kinetic study shows that caspase-3 expression became
      evident at 6th-8th h following anti-Fas stimulation, while early apoptotic cells
      with annexin-V(+)/PI(-) expression appeared at 12th-16th h. IL-15, though
      successful in decreasing apoptosis in pre-activated UCB T cells, failed to
      completely prevent Fas-mediated caspase-3 expression and apoptosis of CB T cells.
      The pre-activated UCB and adult peripheral blood T cells behaved similarly with
      regard to death receptor expression, caspase-3 expression and apoptosis upon Fas
      engagement. Although IL-15 promotes overall activated UCB T-cell survival, it did
      not particularly prevent Fas-mediated activation-induced cell death.

PMID- 18713316
TI  - Polymorphisms within PfMDR1 alter the substrate specificity for anti-malarial
      drugs in Plasmodium falciparum.
AB  - Resistance to several anti-malarial drugs has been associated with polymorphisms
      within the P-glycoprotein homologue (Pgh-1, PfMDR1) of the human malaria parasite
      Plasmodium falciparum. Pgh-1, coded for by the gene pfmdr1, is predominately
      located at the membrane of the parasite's digestive vacuole. How polymorphisms
      within this transporter mediate alter anti-malarial drug responsiveness has
      remained obscure. Here we have functionally expressed pfmdr1 in Xenopus laevis
      oocytes. Our data demonstrate that Pgh-1 transports vinblastine, an established
      substrate of mammalian MDR1, and the anti-malarial drugs halofantrine, quinine
      and chloroquine. Importantly, polymorphisms within Pgh-1 alter the substrate
      specificity for the anti-malarial drugs. Wild-type Pgh-1 transports quinine and
      chloroquine, but not halofantrine, whereas polymorphic Pgh-1 variants, associated
      with altered drug responsivenesses, transport halofantrine but not quinine and
      chloroquine. Our data further suggest that quinine acts as an inhibitor of Pgh-1.
      Our data are discussed in terms of the model that Pgh-1-mediates, in a variant
      specific manner, import of certain drugs into the P. falciparum digestive
      vacuole, and that this contributes to accumulation of, and susceptibility to, the
      drug in question.

PMID- 18713318
TI  - Mutation in the LPS outer core biosynthesis gene, galU, affects LPS interaction
      with the RTX toxins ApxI and ApxII and cytolytic activity of Actinobacillus
      pleuropneumoniae serotype 1.
AB  - Lipopolysaccharides (LPS) and Apx toxins are major virulence factors of
      Actinobacillus pleuropneumoniae, a pathogen of the respiratory tract of pigs.
      Here, we evaluated the effect of LPS core truncation in haemolytic and cytotoxic
      activities of this microorganism. We previously generated a highly attenuated
      galU mutant of A. pleuropneumoniae serotype 1 that has an LPS molecule lacking
      the GalNAc-Gal II-Gal I outer core residues. Our results demonstrate that this
      mutant exhibits wild-type haemolytic activity but is significantly less cytotoxic
      to porcine alveolar macrophages. However, no differences were found in gene
      expression and secretion of the haemolytic and cytotoxic toxins ApxI and ApxII,
      both secreted by A. pleuropneumoniae serotype 1. This suggests that the outer
      core truncation mediated by the galU mutation affects the toxins in their
      cytotoxic activities. Using both ELISA and surface plasmon resonance binding
      assays, we demonstrate a novel interaction between LPS and the ApxI and ApxII
      toxins via the core oligosaccharide. Our results indicate that the GalNAc-Gal II
      Gal I trisaccharide of the outer core is fundamental to mediating LPS/Apx
      interactions. The present study suggests that a lack of binding between LPS and
      ApxI/II affects the cytotoxicity and virulence of A. pleuropneumoniae.

PMID- 18713317
TI  - The RNA binding protein CsrA controls cyclic di-GMP metabolism by directly
      regulating the expression of GGDEF proteins.
AB  - The carbon storage regulator CsrA is an RNA binding protein that controls carbon
      metabolism, biofilm formation and motility in various eubacteria. Nevertheless,
      in Escherichia coli only five target mRNAs have been shown to be directly
      regulated by CsrA at the post-transcriptional level. Here we identified two new
      direct targets for CsrA, ycdT and ydeH, both of which encode proteins with GGDEF
      domains. A csrA mutation caused mRNA levels of ycdT and ydeH to increase more
      than 10-fold. RNA mobility shift assays confirmed the direct and specific binding
      of CsrA to the mRNA leaders of ydeH and ycdT. Overexpression of ycdT and ydeH
      resulted in a more than 20-fold increase in the cellular concentration of the
      second messenger cyclic di-GMP (c-di-GMP), implying that both proteins possess
      diguanylate cyclase activity. Phenotypic characterization revealed that both
      proteins are involved in the regulation of motility in a c-di-GMP-dependent
      manner. CsrA was also found to regulate the expression of five additional
      GGDEF/EAL proteins and a csrA mutation led to modestly increased cellular levels
      of c-di-GMP. All together, these data demonstrate a global role for CsrA in the
      regulation of c-di-GMP metabolism by regulating the expression of GGDEF proteins
      at the post-transcriptional level.

PMID- 18713319
TI  - The final step in the phage infection cycle: the Rz and Rz1 lysis proteins link
      the inner and outer membranes.
AB  - Bacteriophage lambda has four adjacent genes -S, R, Rz and Rz1- dedicated to host
      cell lysis. While S, encoding the holin and antiholin, and R, encoding the
      endolysin, have been intensively studied, the products of Rz and Rz1 have not
      been characterized at either the structural or functional levels. Rz1 is an outer
      membrane lipoprotein and our results indicate that Rz is a type II signal anchor
      protein. Here we present evidence that an Rz-Rz1 complex that spans the periplasm
      carries out the final step in the process of host lysis. These results are
      discussed in terms of a model where endolysin-mediated degradation of the cell
      wall is a prerequisite for conformational changes in the Rz-Rz1 complex leading
      to the juxtaposition and fusion of the IM and OM. Fusion of the two membranes
      removes the last physical barrier to efficient release of progeny virions.

PMID- 18713320
TI  - mRNA processing by RNases J1 and J2 affects Bacillus subtilis gene expression on
      a global scale.
AB  - Ribonucleases J1 and J2 of Bacillus subtilis are evolutionarily conserved enzymes
      combining an endoribonucleolytic and a 5'-3' exoribonucleolytic activity in a
      single polypeptide. Their endoribonucleolytic cleavage specificity resembles that
      of RNase E, a key player in the processing and degradation of RNA in Escherichia
      coli. The biological significance of the paralogous RNases J1 and J2 in Bacillus
      subtilis is still unknown. Based on the premise that cleavage of an mRNA might
      alter its stability and hence its abundance, we have analysed the transcriptomes
      and proteomes of single and double mutant strains. The absence or decrease of
      both RNases J1 and J2 together profoundly alters the expression level of hundreds
      of genes. By contrast, the effect on global gene expression is minimal in single
      mutant strains, suggesting that the two nucleases have largely overlapping
      substrate specificities. Half-life measurements of individual mRNAs show that
      RNases J1/J2 can alter gene expression by modulating transcript stability. The
      absence/decrease of RNases J1 and J2 results in similar numbers of transcripts
      whose abundance is either increased or decreased, suggesting a complex role of
      these ribonucleases in both degradative and regulatory processing events that
      have an important impact on gene expression.

PMID- 18713321
TI  - Usefulness of nonlinear analysis of ECG signals for prediction of inducibility of
      sustained ventricular tachycardia by programmed ventricular stimulation in
      patients with complex spontaneous ventricular arrhythmias.
AB  - INTRODUCTION: The aim of our study was to assess the effectiveness of the
      nonlinear analysis (NLA) of ECG in predicting the results of invasive
      electrophysiologic study (EPS) in patients with ventricular arrhythmias. METHODS:
      We evaluated 25 patients with history of cardiac arrest, syncope, sustained, or
      nonsustained ventricular tachycardia (VT). All patients underwent
      electrophysiologic study (EPS) and nonlinear analysis (NLA) of ECG. The study
      group was compared with a control group of 25 healthy subjects, in order to
      define the normal range of NLA. ECG was processed in order to obtain numerical
      values, which were analyzed by nonlinear mathematical functions. Patients were
      classified through the application of a clustering procedure to the whole set of
      functions, and the correlation between the results of nonlinear analysis of ECG
      and EPS was tested. RESULTS: NLA assigned all patients with negative EPS to the
      same class of healthy subjects, whereas the patients in whom VT was inducible had
      been correctly and clearly isolated into a separate cluster. In our study, the
      result of NLA with application of the clustering technique was significantly
      correlated to that of EPS (P < 0.001), and was able to predict the result of EPS,
      with a negative predictive value of 100% and a positive predictive value of 100%.
      CONCLUSIONS: NLA can predict the results of EPS with good negative and positive
      predictive value. However, further studies are needed in order to verify the
      usefulness of this noninvasive tool for sudden death risk stratification in
      patients with ventricular arrhythmias.

PMID- 18713322
TI  - Beat-to-beat QT interval variability is primarily affected by the autonomic
      nervous system.
AB  - BACKGROUND: Beat-to-beat QT interval variability is associated with life
      threatening arrhythmias and sudden death, however, its precious mechanism and the
      autonomic modulation on it remains unclear. The purpose of this study was to
      determine the effect of drugs that modulate the autonomic nervous system on beat
      to-beat QT interval. METHOD: RR and QT intervals were determined for 512
      consecutive beats during fixed atrial pacing with and without propranolol and
      automatic blockade (propranolol plus atropine) in 11 patients without structural
      heart disease. Studied parameters included: RR, QTpeak (QRS onset to the peak of
      T wave), QTend (QRS onset to the end of T wave) interval, standard deviation (SD)
      of the RR, QTpeak, and QTend (RR-SD, QTpeak-SD, and QTend-SD), coefficients of
      variation (RR- CV, QTpeak-CV, and QTend-CV) from time domain analysis, total
      power (TP; RR-TP, QTpeak-TP, and QTend-TP), and power spectral density of the low
      frequency band (LF; RR-LF, QTpeak-LF, and QTend-LF) and the high-frequency band
      (HF; RR-HF, QTpeak-HF and QTend-HF). RESULTS: Administration of propranolol and
      infusion of atropine resulted in the reduction of SD, CV, TP, and HF of the QTend
      interval when compared to controlled atrial pacing (3.7 +/- 0.6 and 3.5 +/- 0.5
      vs 4.8 +/- 1.4 ms, 0.9 +/- 0.1 and 0.9 +/- 0.1 vs 1.2 +/- 0.3%, 7.0 +/- 2.2 and
      7.0 +/- 2.2 vs 13.4 +/- 8.1 ms(2), 4.2 +/- 1.4 and 4.2 +/- 1.2 vs 8.4 +/- 4.9
      ms(2), respectively). Administration of propranolol and atropine did not affect
      RR interval or QTpeak interval indices during controlled atrial pacing.
      CONCLUSIONS: Beat-to-beat QT interval variability is affected by drugs that
      modulate the autonomic nervous system.

PMID- 18713324
TI  - Heart rate variability in middle-aged men with new-onset hypertension.
AB  - BACKGROUND: It has been well established that hypertension is associated with
      autonomic dysregulation. Studies investigating HRV have established that
      hypertension is characterized by sympathetic overactivity and or attenuation of
      parasympathetic modulation of the heart. METHODS: We examined short-term heart
      rate variability (HRV) as well as conventional indices of cardiovascular
      autonomic function including heart rate variation during deep breathing (HRVdb),
      30: 15 ratio, pressor response to quiet standing and isometric handgrip in 35
      male subjects (39 +/- 7 year, mean +/- SD) with new-onset hypertension (resting
      BP 155 +/- 17/101 +/- 8 mm Hg) and 17 age-matched normotensive men (resting BP:
      111 +/- 7/71 +/- 5 mmHg). RESULTS: HRVdb was significantly lower in hypertensives
      (21 +/- 8) compared to normotensives (mean age 36 +/- 7, P = 0.03). Differences
      in mean RR were insignificant, logarithm of high-frequency (HF) spectral power of
      RR intervals was significantly lower in hypertensives compared to normotensives
      in the supine position (P = 0.02). CONCLUSIONS: Our data suggest that new-onset
      hypertension is characterized by diminished short-term HRV, possibly due to an
      increase in cardiovascular sympathovagal balance.

PMID- 18713325
TI  - Abnormal heart rate variability and subtle atrial arrhythmia in patients with
      familial amyloidotic polyneuropathy.
AB  - BACKGROUND: Cardiac autonomic dysfunction is a common complication of familial
      amyloidotic polyneuropathy (FAP), but cardiac arrhythmia and conduction
      disturbances are also common. We analyzed heart rate variability (HRV) in FAP
      patients using power spectrum analysis and Poincare plot analysis. METHODS: HRV
      was analyzed in 24-hour ECG recordings (Holter) in 41 FAP patients. RESULTS:
      Power spectrum analysis showed reduced HRV in 21 FAP patients. A novel finding
      was that nine other patients with abnormal Poincare plots had either very high
      power in the high-frequency region (0.15-0.50 Hz) or broadband HRV power spectra
      without any distinctive spectral peaks. Reanalysis of their ECGs showed a
      previously undetected intermittent atrial arrhythmia. CONCLUSIONS: Subtle
      arrhythmias may be difficult to detect during analyses of Holter recordings.
      Patients with intermittent atrial arrhythmia were identified by broadband HRV
      spectra and abnormal Poincare plots. High high-frequency power in HRV and
      irregular heart rate patterns may indicate the presence of subtle atrial
      arrhythmia. Consequently, such patients should be excluded from studies of
      cardiac autonomic modulation.

PMID- 18713323
TI  - Phenotypic variability in Caucasian and Japanese patients with matched LQT1
      mutations.
AB  - BACKGROUND: Ethnic differences may affect the phenotypic expression of genetic
      disorders. However, data regarding the effect of ethnicity on outcome in patients
      with genetic cardiac disorders are limited. We compared the clinical course of
      Caucasian and Japanese long QT type-1 (LQT1) patients who were matched for
      mutations in the KCNQ1 gene. METHODS: The study population comprised 62 Caucasian
      and 38 Japanese LQT1 patients from the International LQTS Registry who were
      identified as having six identical KCNQ1 mutations. The biophysical function of
      the mutations was categorized into dominant-negative (> 50%) or
      haploinsufficiency (< or =50%) reduction in cardiac repolarizing IKs potassium
      channel current. The primary end point of the study was the occurrence of a first
      cardiac event from birth through age 40 years. RESULTS: Japanese patients had a
      significantly higher cumulative rate of cardiac events (67%) than Caucasian
      patients (39%; P = 0.01). The respective frequencies of dominant negative
      mutations in the two ethnic groups were 63% and 28% (P < 0.001). In multivariate
      analysis, Japanese patients had an 81% increase in the risk of cardiac events (P
      = 0.06) as compared with Caucasians. However, when the biophysical function of
      the mutations was included in the multivariate model, the risk associated with
      Japanese ethnicity was no longer evident (HR = 1.05; P = 0.89). Harboring a
      dominant negative mutation was shown to be the most powerful and significant
      predictor of outcome (HR = 3.78; P < 0.001). CONCLUSIONS: Our data indicate that
      ethnic differences in the clinical expression of LQTS can be attributed to the
      differences in frequencies of the specific mutations within the two populations.

PMID- 18713326
TI  - Sympathetic overactivity in patients with pulmonary stenosis and improvement
      after percutaneous balloon valvuloplasty.
AB  - OBJECTIVE: Percutaneous balloon valvulotomy (PBV) is the procedure of choice for
      the treatment of valvular pulmonary stenosis (PS) with similar results comparable
      to surgical valvotomy but less invasive. METHODS AND RESULTS: Twenty-seven
      consecutive patients with PS being evaluated for PBV were enrolled in the study.
      Peak instantaneous transvalvular gradient, right ventricle (RV) diameter, mean
      atrial pressures, RV systolic pressure (RVSP), pro-brain natriuretic peptide
      (proBNP) levels significantly decreased immediately after PBV. Regarding heart
      rate variability (HRV) parameters, mean HR (heart rate), LF (low frequency) day
      and night, LF/HF day and night significantly decreased and standard deviation of
      all NN intervals (SDNN), root mean square of successive differences (RMSSD), P
      number of NN intervals that differed by more than 50 ms from adjacent interval
      divided by the total number of all NN intervals (PNN50), HF (High frequency) day
      and night significantly increased 1 day after PBV and these changes were shown to
      be preserved at the first month. The increase in SDNN was correlated with the
      decrease in right atrial pressure (RAP) (r =-0.5, P = 0.04); the increase in
      standard deviation of the 5-minute mean RR intervals (SDANN) was correlated with
      the decrease in proBNP (r =-0.4, P = 0.03). CONCLUSIONS: Sympathetic overactivity
      and increased proBNP levels were associated with the symptomatic status of
      patients with PS. Associated with a decrease in atrial pressures and proBNP
      levels, PBV yielded a decrease in adrenergic overactivity in the patients with
      PS.

PMID- 18713327
TI  - Prevalence of supraventricular tachyarrhythmias in a cohort of 115 patients with
      Brugada syndrome.
AB  - BACKGROUND: The Brugada syndrome is characterized by ST segment elevation in
      leads V(1) to V(3) and a right bundle branch block like pattern. It is associated
      with an increased risk of syncope and sudden cardiac death. Initial reports in
      small numbers of patients suggest an association between supraventricular
      tachycardias and Brugada syndrome with a prevalence varying between 13% and 40%.
      OBJECTIVE: Aim of this study was to evaluate the prevalence of AV nodal reentrant
      tachycardia, AV reentry tachycardia, and/or atrial fibrillation in a large cohort
      of patients diagnosed as Brugada syndrome. METHODS AND RESULTS: From three
      different European centers 115 consecutive patients with a Brugada syndrome were
      evaluated noninvasively and invasively (mean age 45 +/- 12 years, n = 82 men, n =
      33 women). Nineteen of 115 patients (17%) had a history of previous cardiac
      arrest. Syncope was reported by 58 patients (50%), 33 patients had a positive
      family history of sudden cardiac death (29%). Supraventricular tachycardias were
      documented in 26 of the patients (23%): Eight patients (7%) had AV-nodal
      reentrant tachycardias and two patients had AV-reentry tachycardias; atrial
      tachycardias were documented in three patients, and another 13 patients (11%)
      suffered from atrial fibrillation/atrial flutter. Additionally, atrial
      fibrillation was inducible by programmed atrial stimulation in nine patients
      (8%). CONCLUSIONS: Supraventricular tachycardias occur in 23% of patients with
      Brugada syndrome. Documentation of atrial fibrillation especially in the young or
      supraventricular tachycardias associated with syncope should give reason to
      screen for Brugada syndrome.

PMID- 18713328
TI  - Reproducibility and gender-related differences of heart rate variability during
      all-day activity in young men and women.
AB  - BACKGROUND: Only few data are available on reproducibility over time in healthy
      young men and women and the corresponding gender-related changes of heart rate
      variability (HRV) measurements. METHODS: We studied temporal and spectral HRV
      indices obtained from 24-hour Holter recordings in 32 healthy volunteers (14 men
      and 18 women, mean age 29 +/- 3 years) during 2 days of their usual all-day
      activity. RESULTS: Time-domain measures and the spectral low-frequency (LF) and
      high-frequency (HF) components as well as the LF/HF ratio were comparable on both
      test days. Significantly higher values on test day 2 were observed only for the
      spectral very-low-frequency (VLF) component and for the resulting total power.
      Compared to men, women had higher day- and nighttime vagus-associated HRV
      indices, including root mean square of successive differences (RMSSD), pNN50
      (NN50 count divided by the total number of all NN intervals), and HF power, and
      lower day- and nighttime VLF and LF power with lower LF/HF ratio and total power.
      CONCLUSIONS: Temporal indices and the LF and HF spectral HRV measures are
      reproducible over usual all-day activity in young healthy subjects. Young women
      have higher day-and nighttime vagal tone than men with similar age range.

PMID- 18713329
TI  - The impact of preinfarction angina on electrocardiographic ischemia grades in
      patients with acute myocardial infarction treated with primary percutaneous
      coronary intervention.
AB  - OBJECTIVE: Grade 3 ischemia (G3I) is defined as ST elevation with distortion of
      the terminal portion of the QRS (emergence of the J point > 50% of the R wave in
      leads with qR configuration, or disappearance of the S wave in leads with an Rs
      configuration). Patients with G3I on the presenting electrocardiogram (ECG) had
      worse prognosis than the patients with lesser (grade 2-G2I) ischemia. The aim of
      this study is to examine the effects of preinfarct angina (PIA) on
      electrocardiographic ischemia grades. METHODS: One hundred forty-eight
      consecutive patients with ST-segment myocardial infarction (STEMI) were included
      in this study. All patients underwent primary percutaneous coronary intervention.
      The admission ECGs was analyzed retrospectively for electrocardiographic ischemia
      grades and compared with the presence of PIA. RESULTS: Study population consisted
      of 110 patients with G2I (88 men, mean age = 63 +/- 6 years) and 38 patients with
      G3I (32 men, mean age = 61 +/- 8 years). Baseline characteristics of the groups
      were the same except for patients with G3I had significantly longer pain to
      balloon time and higher admission creatine kinase MB isoenzyme (CK-MB) levels.
      Tissue myocardial perfusion grade (TMPG) was better in patients with G2I. While
      18 patients (47%) with G3I had PIA, 81 patients (70%) with G2I had PIA (P =
      0.005). Although pain to balloon time and admission CK-MB were independent
      predictor of worse electrocardiographic ischemia grade (OR 1.69, 95% CI 1.09
      2.62; P = 0.01; OR 1.01, 1.00-1.02, P = 0.04), PIA and left ventricular ejection
      time (LVEF) were independent predictors of better electrocardiographic ischemia
      grade (OR 0.4, 95% CI 0.17-0.90; P = 0.02, OR 0.92, 95% CI 0.85-0.99; P = 0.03,
      respectively) in multivariate logistic regression analysis. CONCLUSION: PIA is
      one of the most important clinical predictors of better ischemia grades
      especially when combined with the pain to balloon time, LVEF, and admission CK-MB
      levels in patients with STEMI. This study provided another evidence for the
      protective effects of PIA.

PMID- 18713330
TI  - Cumulative burden of atherosclerotic risk genotypes and the age at onset of a
      first myocardial infarction: a case-only carriership approach.
AB  - BACKGROUND: Previously identified atherosclerotic genetic factors have been
      studied mostly in case-control studies and in nonuniform ethnic populations,
      whereas data on the cumulative contribution of genetic factors to an earlier
      onset of a first myocardial infarction (MI) are limited. We hypothesized that
      several genetic atherosclerotic single nucleotide polymorphisms (SNPs) may exert
      an additive effect on the earlier occurrence of coronary atherothrombotic disease
      after adjustment for clinical factors. METHODS: Eighteen atherosclerotic high
      risk SNPs were selected based upon meta-analyses of 614 published reports, and
      were incorporated into a carriership model. Multivariate regression analysis was
      used to identify the independent contribution of selected genotypes to the age at
      onset of a first MI in a cohort of 814 white (n = 622) and nonwhite (n = 192)
      patients enrolled in the Thrombogenic Factors and Coronary Events Study. RESULTS:
      The analysis demonstrated that selected genotypes were significantly associated
      with an earlier occurrence of a first MI among white patients (an average of 0.6
      year reduction per carried genotype; P = 0.027), whereas the contribution of
      genotypes to MI onset among nonwhite patients was not significant (an average of
      0.7 year increase per carried genotype; P = 0.16), with a significant ethnic x
      genotype interaction effect (P = 0.02). CONCLUSIONS: Our findings suggest that
      currently identified atherosclerotic genetic factors confer an independent
      additive contribution to the earlier onset of coronary atherothrombotic disease
      among white patients. The lack of a significant association between these
      genotypes and outcome in other ethnic groups suggests that cardiovascular genetic
      risk should be studied directly in these populations.

PMID- 18713331
TI  - Electrocardiographic transmural dispersion of repolarization in patients with
      inherited short QT syndrome.
AB  - BACKGROUND: Short QT syndrome (SQTS) carries an increased risk for sudden cardiac
      death. However, only a short QT interval does not express the risk of ventricular
      arrhythmias. Thus, additional evaluation of the repolarization abnormality in
      SQTS patients is essential. In experimental models of SQTS, increased transmural
      dispersion of repolarization (TDR) and its electrocardiographic counterpart T
      wave peak to T-wave end interval (TPE) appeared critical for induction of
      polymorphic ventricular tachycardia (PMVT). In a clinical study with acquired
      long QT syndrome patients, TPE/QT ratio > 0.28 indicated arrhythmia risk. We
      hypothesized that the TPE/QT ratio would be greater in SQTS patients than in
      control subjects. METHODS AND RESULTS: We compared the behavior of the
      electrocardiographic TDR in three seriously symptomatic SQTS patients of unknown
      genotype presenting baseline QTc values < 320 ms and in nine healthy age-matched
      control subjects. We determined QT and TPE intervals as well as TPE/QT ratio from
      24-hour ECG recordings using a computer-assisted program. Diurnal average of
      TPE/QT ratio was 0.28 +/- 0.03 in SQTS patients and 0.21 +/- 0.02 in control
      subjects (P = 0.01). SQTS patients had also lesser capacity to change TPE
      intervals from steady-state conditions to abrupt maximal values than control
      subjects. CONCLUSION: SQTS patients have increased and autonomically uncontrolled
      electrocardiographic TDR. According to experimental SQTS models, the present
      results may in part explain increased vulnerability of SQTS patients to
      ventricular arrhythmias.

PMID- 18713332
TI  - Ionic mechanisms and vectorial model of early repolarization pattern in the
      surface electrocardiogram of the athlete.
AB  - BACKGROUND: The electrocardiogram (ECG) of the athlete displays particular
      characteristics as a consequence of both electrophysiological and autonomic
      remodeling of the heart that follows continued physical training. However, doubts
      persist on how these changes directly interact during ventricular activation and
      repolarization ultimately affecting surface ECG waveforms in athletes. OBJECTIVE:
      This article considers an in deep rationale for the electrocardiographic pattern
      known as early repolarization based on both electrophysiological mechanisms at
      cellular level and the vectorial theory of the cardiac activation. METHODS: The
      mechanism by which the autonomic remodeling influences the cardiac electrical
      activation is reviewed and an insight model of the ventricular repolarization
      based on ionic models and the vectorial theory of the cardiac activation is
      proposed. RESULTS: Considering the underlying processes related to ventricular
      electrical remodeling, we propose that, in athletes' heart: 1) vagal modulation
      increases regional electrophysiological differences in action potential phases 1
      and 2 amplitudes, thus enhancing a voltage gradient between epicardial and
      endocardial fibers; 2) this gradient affects depolarization and repolarization
      timing sequences; 3) repolarization wave front starts earlier on ventricular wall
      and partially overcomes the end of depolarization causing an upward displacement
      of the J-point, ST segment elevation, and inscription of magnified T-waves
      amplitudes leading to characteristic surface ECG waveform patterns. CONCLUSIONS:
      In athletes, the association between epicardial to endocardial
      electrophysiological differences and early repolarization ECG pattern can be
      demonstrated by the vectorial theory of the ventricular activation and
      repolarization.

PMID- 18713333
TI  - The year of 2007 in electrocardiology.

PMID- 18713334
TI  - QRS alternans with 2:1 atrioventricular conduction block: what is the mechanism?
AB  - An 81-year-old woman was admitted for symptomatic bradycardia. On admission, the
      ECG exhibited QRS alternans, narrow QRS complex and left bundle branch block with
      2:1 AV block. The patient soon had complete AV block and underwent a pacemaker
      implantation. An appropriate mechanism for explaining those ECG findings might be
      4:1 conduction over the left bundle branch and 2:1 conduction over the right
      bundle branch. An ECG pattern exhibiting QRS alternans with a narrow QRS complex
      and bundle branch block with 2:1 AV block may suggest the coexistence of both
      bundle branch blocks and a high risk of complete AV block.

PMID- 18713335
TI  - Atrial repolarization causing psuedoprolongation of the QT interval.

PMID- 18713336
TI  - Athletes, ventricular arrhythmias, electrophysiological testing, microvolt T-wave
      alternans, and a follow-up of 30 +/- 21 months: a need for follow-up updates.

PMID- 18713338
TI  - Pediatric Allergy and Immunology. In this issue.

PMID- 18713339
TI  - Allergic gastrointestinal motility disorders in infancy and early childhood.
AB  - Gastro-oesophageal reflux disease, constipation and colic are among the most
      common disorders in infancy and early childhood. In at least a subset of infants
      with these functional disorders, improvement after dietary elimination of
      specific food proteins has been demonstrated. Gastrointestinal food allergy
      should therefore be considered in the differential diagnosis of infants
      presenting with persistent regurgitation, constipation or irritable behaviour,
      particularly if conventional treatment has not been beneficial. The diagnosis of
      food protein-induced gastrointestinal motility disorders is hampered by the
      absence of specific clinical features or useful laboratory markers.
      Gastrointestinal biopsies before commencing a hypoallergenic diet may provide the
      most important diagnostic clues. Early recognition is essential for the optimal
      management of these patients to prevent nutritional sequelae or aversive feeding
      behaviours. Treatment relies on hypoallergenic formulae, as well as maternal
      elimination diets in breast-fed infants. Further research is required to better
      define the pathological mechanisms and diagnostic markers of paediatric allergic
      gastrointestinal motility disorders. The following article will present three
      instructive cases followed by discussion of the clinical presentation, diagnosis,
      treatment and natural history of food allergic motility disorders in infancy and
      early childhood.

PMID- 18713340
TI  - Testing for hypothalamic-pituitary-adrenal axis suppression in asthmatic
      children.

PMID- 18713342
TI  - Homologous comparisons of photosynthetic system I genes among cyanobacteria and
      chloroplasts.
AB  - It has now believed that chloroplasts arose from cyanobacteria, however, during
      endosymbiosis, the photosynthetic genes in chloroplasts have been reduced. How
      these changes occurred during plant evolution was the focus of the present study.
      Beginning with photosystem I (PSI) genes, a homologous comparison of amino acid
      sequences of 18 subunits of PSI from 10 species of cyanobacteria, chloroplasts in
      12 species of eucaryotic algae, and 28 species of plants (including bryophytes,
      pteridophytes, gymnospermae, dicotyledon and monocotyledon) was undertaken. The
      data showed that 18 genes of PSI can be divided into two groups: Part I including
      seven genes (psaA, psaB, psaC, psaI, psaJ, ycf3 and ycf4) shared both by
      cyanobacteria and plant chloroplasts; Part II containing another 11 genes (psaD,
      psaE, psaF, psaK, psaL, psaM, btpA, ycf37, psaG, psaH and psaN) appeared to have
      diversified in different plant groups. Among Part I genes, psaC, psaA and psaB
      had higher homology in all species of cyanobacteria and chloroplasts. Among Part
      II genes, only psaG, psaH and psaN emerged in seed plants.

PMID- 18713343
TI  - A genetic map constructed using a doubled haploid population derived from two
      elite Chinese common wheat varieties.
AB  - Genetic mapping provides a powerful tool for the analysis of quantitative trait
      loci (QTLs) at the genomic level. Herein, we report a new genetic linkage map
      developed from an F(1)-derived doubled haploid (DH) population of 168 lines,
      which was generated from the cross between two elite Chinese common wheat
      (Triticum aestivum L.) varieties, Huapei 3 and Yumai 57. The map contained 305
      loci, represented by 283 simple sequence repeat (SSR) and 22 expressed sequence
      tag (EST)-SSR markers, which covered a total length of 2141.7 cM with an average
      distance of 7.02 cM between adjacent markers on the map. The chromosomal
      locations and map positions of 22 new SSR markers were determined, and were found
      to distribute on 14 linkage groups. Twenty SSR loci showed different chromosomal
      locations from those reported in other maps. Therefore, this map offers new
      information on the SSR markers of wheat. This genetic map provides new
      opportunities to detect and map QTLs controlling agronomically important traits.
      The unique features of this map are discussed.

PMID- 18713344
TI  - Localization and dynamic change of saikosaponin in root of Bupleurum chinense.
AB  - Anatomical, histochemical and phytochemical methods were used to investigate the
      structure, the localization and content changes of total saikosaponin and
      saikosaponin-a of the roots of Bupleurum chinense DC. at different developmental
      stages. Results showed that saikosaponin was mainly distributed in pericycle and
      primary phloem in the young root; but in the mature root, it was mainly
      distributed in vascular cambium and secondary phloem. During the whole growth
      period from the pre-blossom, blossom, fruit, and fruit mature periods until the
      pre-withering period, it was in the fruit mature period that both the total
      saikosaponin content and the saikosaponin-a content reached the highest level. So
      the last 20 d of October was considered as the right collecting season for the
      drug of B. chinense. In addition, the quality of 1-year-old drug was better than
      that of 2-year-old drug due to its higher saikosaponin content. On the other
      hand, judging from the external characteristics of the drug, the one with an
      acerose taproot and more lateral roots was of better quality. The results offered
      theoretical bases for selecting medicinal material of high quality and
      determining the most appropriate harvesting stage and part of B. chinense.

PMID- 18713345
TI  - Nicotine concentration in leaves of flue-cured tobacco plants as affected by
      removal of the shoot apex and lateral buds.
AB  - It is believed that the nicotine concentration in tobacco is closely correlated
      with the amount of nitrogen (N) supplied. On the other hand, N uptake mainly
      occurs at the early growth stage, whereas nicotine concentration increases at the
      late growth stage, especially after removing the shoot apex. To identify the
      causes of the increased nicotine concentration in tobacco plants, and to compare
      the effects of different ways of mechanical wounding on nicotine concentration,
      field experiments were carried out in Fuzhou, Fujian Province in 2003 and 2004.
      Excision of the shoot apex had almost no influence on N content in the plant;
      however, it caused dramatic increases in nicotine concentration in leaves,
      especially in the middle and upper leaves. An additional increase of the nicotine
      concentration was obtained by removal of axillary buds. The wounding caused by
      routine leaf harvests, however, did not change the leaf nicotine concentration,
      and neither did reducing leaf harvest times. The present results revealed no
      direct relationship between N supply and nicotine concentration in tobacco
      leaves, and indicate that not all kinds of mechanical wounding were capable of
      stimulating nicotine synthesis in tobacco plants. Since nicotine production is
      highly dependent on the removal of apical meristems and hence on the major
      sources of auxin in the plant, and application of 1-naphthylacetic acid onto the
      cut surface of the stem after removing the shoot apex markedly decreased the
      nicotine concentration in different leaves and the total nicotine content in the
      plant, the results suggest that decreased auxin supply caused by removal of the
      shoot apex as a kind of mechanical wounding might regulate nicotine synthesis in
      the roots of tobacco plants.

PMID- 18713346
TI  - Isolation and characterization of a C-repeat binding transcription factor from
      maize.
AB  - C-repeat binding proteins (CBFs) are a group of transcription factors that have
      been proven to be important for stress tolerance in plants. Many of these
      transcription factors transactivate the promoters of cold-regulated genes via
      binding to low temperature- or dehydration-responsive cis-elements, thus
      conferring plants cold acclimation. In the present study, we isolated a C-repeat
      binding transcription factor from maize using the yeast one-hybrid system with
      the C-repeat motif from the promoter of the Arabidopsis COR15a gene as bait. The
      isolated transcription factor is highly similar to the Arabidopsis CBF3 in their
      predicted amino acid sequences, and is therefore designated ZmCBF3. Point
      mutation analyses of the ZmCBF3-binding cis-element revealed (A/G)(C/T)CGAC as
      the core binding sequence. Expression analyses showed that ZmCBF3 was upregulated
      by both abscisic acid and low temperature, and was actively expressed during
      embryogenesis, suggesting that ZmCBF3 plays a role in stress response in maize.

PMID- 18713347
TI  - Establishment of Withania somnifera hairy root cultures for the production of
      withanolide A.
AB  - Withania sominifera (Indian ginseng) was transformed by Agrobacterium rhizogenes.
      Explants from seedling roots, stems, hypocotyls, cotyledonary nodal segments,
      cotyledons and young leaves were inoculated with A. rhizogenes strain R1601.
      Hairy (transformed) roots were induced from cotyledons and leaf explants. The
      transgenic status of hairy roots was confirmed by polymerase chain reaction using
      nptII and rolB specific primers and, subsequently, by Southern analysis for the
      presence of nptII and rolB genes in the genomes of transformed roots. Four clones
      of hairy roots were established; these differed in their morphology. The doubling
      time of faster growing cultures was 8-14 d with a fivefold increase in biomass
      after 28 d compared with cultured, non-transformed seedling roots. MS-based
      liquid medium was superior for the growth of transformed roots compared with
      other culture media evaluated (SH, LS and N6), with MS-based medium supplemented
      with 40 g/L sucrose being optimal for biomass production. Cultured hairy roots
      synthesized withanolide A, a steroidal lactone of medicinal and therapeutic
      value. The concentration of withanolide A in transformed roots (157.4 microg/g
      dry weight) was 2.7-fold more than in non-transformed cultured roots (57.9
      microg/g dry weight).

PMID- 18713348
TI  - Difference in tree growth responses to climate at the upper treeline: Qilian
      Juniper in the Anyemaqen Mountains.
AB  - Three ring-width chronologies were developed from Qilian Juniper (Sabina
      przewalskii Kom.) at the upper treeline along a west-east gradient in the
      Anyemaqen Mountains. Most chronological statistics, except for mean sensitivity
      (MS), decreased from west to east. The first principal component (PC1) loadings
      indicated that stands in a similar climate condition were most important to the
      variability of radial growth. PC2 loadings decreased from west to east,
      suggesting the difference of tree-growth between eastern and western Anyemaqen
      Mountains. Correlations between standard chronologies and climatic factors
      revealed different climatic influences on radial growth along a west-east
      gradient in the study area. Temperature of warm season (July-August) was
      important to the radial growth at the upper treeline in the whole study area.
      Precipitation of current May was an important limiting factor of tree growth only
      in the western (drier) upper treeline, whereas precipitation of current September
      limited tree growth in the eastern (wetter) upper treeline. Response function
      analysis results showed that there were regional differences between tree growth
      and climatic factors in various sampling sites of the whole study area.
      Temperature and precipitation were the important factors influencing tree growth
      in western (drier) upper treeline. However, tree growth was greatly limited by
      temperature at the upper treeline in the middle area, and was more limited by
      precipitation than temperature in the eastern (wetter) upper treeline.

PMID- 18713349
TI  - Lycopene accumulation affects the biosynthesis of some carotenoid-related
      volatiles independent of ethylene in tomato.
AB  - For elucidating the regulatory mechanism of ethylene on carotenoid-related
      volatiles (open chain) compounds and the relationship between lycopene and
      carotenoid-related volatiles, transgenic tomato fruits in which ACC synthase was
      suppressed were used. The transgenic tomato fruit showed a significant reduction
      of lycopene and aroma volatiles with low ethylene production. 6-Methyl-5-hepten-2
      one, 6-methyl-5-hepten-2-ol and geranylacetone, which were suspected to be
      lycopene degradation products, were lower than those in wild type tomato fruits.
      In order to identify whether lycopene accumulation effects the biosynthesis of
      some carotenoid-related volatiles independent of ethylene in tomato or not, the
      capability of both wild type and transgenic tomato fruits discs to convert
      lycopene into carotenoid-related volatiles was evaluated. The data showed that
      external lycopene could convert into 6-methyl-5-hepten-2-one and 6-methyl-5
      hepten-2-ol in vivo, indicating that the strong inhibition of ethylene production
      had no effect on enzymes in the biosynthesis pathway of some carotenoid-related
      volatiles. Therefore, in ACS-suppression transgenic tomato fruits, the low levels
      of 6-methyl-5-hepten-2-one, 6-methyl-5-hepten-2-ol was due to decreased lycopene
      accumulation, not ethylene production. Ethylene only affected the accumulation of
      lycopene, and then indirectly influenced the level of lycopene-related volatiles.

PMID- 18713350
TI  - Seasonal and tissue age influences on endophytic fungi of Pinus tabulaeformis
      (Pinaceae) in the Dongling Mountains, Beijing.
AB  - Endophytic fungi associated with Pinus tabulaeformis Carr. were investigated in
      the Dongling Mountains of Beijing. A total of 16,200 tissue segments of P.
      tabulaeformis from four sample collections were processed, and 10,659 fungal
      isolates were recovered. The overall colonization and isolation rates of
      endophytic fungi from high to low were spring > winter > autumn > summer and in
      different tissues were bark > needle > xylem, irrespective of sampling seasons.
      The colonization rates of endophytic fungi of needles increased with age in the
      four sample collections. There were no significant differences of the
      colonization rates of endophytic fungi among 1-, 2-, and 3-year-old bark and
      xylem, except for significantly lower colonization rates in 1-year-old bark than
      in 2- and 3-year-old bark in summer. A similar trend of the isolation rates of
      endophytic fungi occurred. A total of 24 fungal taxa were recorded, of these five
      taxa Alternaria alternata, Leptostroma sp., Pestalotiopsis besseyi, Phoma lingam,
      and Phomopsis archeri, were consistently isolated as the common fungi in each
      sample collection. Our results suggest that some fungi show a certain degree of
      tissue recurrence or specificity, and the composition of endophytic assemblages
      is not conspicuously influenced by the seasonal factor.

PMID- 18713351
TI  - Genetic diversity and association analysis for salinity tolerance, heading date
      and plant height of barley germplasm using simple sequence repeat markers.
AB  - The objective of this study was to investigate the genetic diversity of barley
      accessions. Additionally, association trait analysis was conducted for grain
      yield under salinity, heading date and plant height. For this purpose, 48 barley
      genotypes were analyzed with 22 microsatellite simple sequence repeat (SSR)
      markers. Four of the 22 markers (Bmac316, scssr03907, HVM67 and Bmag770) were
      able to differentiate all barley genotypes. Cluster and principal coordinate
      analysis allowed a clear grouping between countries from the same region. The
      genotypes used in this study have been evaluated for agronomic performance in
      different environments. Conducting association analysis for grain yield under
      salinity conditions using TASSEL software revealed a close association of the
      marker Bmag749 (2H, bin 13) in two different environments with common significant
      alleles (175, 177), whereas the HVHOTR1 marker (2H, bin 3) was only significant
      in Sakhar_Egypt with alleles size being 158 and 161. Heading date also showed an
      association with scssr03907 through the common significant specific allele 111
      and EBmac0415 markers in three different agro climatic locations, whereas HVCMA,
      scssr00103 and HVM67 were linked to heading date in the Egyptian environment
      only. The plant height association analysis revealed significant markers Bmag770
      via the significant allele 152 and scssr09398.

PMID- 18713352
TI  - Effects of light on the growth and clonal reproduction of Ligularia virgaurea.
AB  - Ligularia virgaurea is a perennial herb that is widely distributed in the alpine
      meadow on the eastern Qinghai-Tibet plateau. We investigated the patterns of
      growth and reproduction of L. virgaurea under two contrasting levels of light
      conditions for two continuous growing seasons. Our results showed that the light
      effects on the maximum relative growth rate, the shoot weight ratio and the root
      weight ratio differed between the two growing seasons. L. virgaurea reproduced
      initially through rhizome in the second growing season, rather than sexual
      reproduction. The proportion of genets with clonal reproduction decreased under
      shaded conditions. A minimum genet size should be attained for clonal
      reproduction to begin under the shaded conditions. There was a positive linear
      relationship between clonal reproduction and genet size. Light level affected the
      allocation of total biomass to clonal structures, with less allocation under the
      full natural irradiance than under the shaded conditions. There seemed to be a
      trade-off between vegetative growth and clonal reproduction under the full
      natural irradiance, in terms of smaller relative growth rates of genets with
      clonal reproduction than those without clonal reproduction. L. virgaurea
      emphasized clonal reproduction under the full natural irradiance, while the plant
      emphasized vegetative growth under the shaded conditions.

PMID- 18713353
TI  - Increased maleness at flowering stage and femaleness at fruiting stage with size
      in an andromonoecious perennial, Veratrum nigrum.
AB  - Theory predicts that cosexual plants should adjust their resource investment in
      male and female functions according to their size if female and male fitness are
      differentially affected by size. However, few empirical studies have been carried
      out at both the flowering and fruiting stages to adequately address size
      dependent sex allocation in cosexual plants. In this paper, we investigated
      resource investment between female and male reproduction, and their size
      dependence in a perennial andromonoecious herb, Veratrum nigrum L. We sampled 192
      flowering plants, estimated their standardized phenotypic gender, and assessed
      the resource investment in male and female functions in terms of absolute dry
      biomass. At the flowering stage, male investment increased with plant size more
      rapidly than female investment, and the standardized phenotypic femaleness
      (ranging from 0.267 to 0.776) was negatively correlated with plant size. By
      contrast, female biased allocation was found at the fruiting stage, although both
      flower biomass and fruit biomass were positively correlated with plant size. We
      propose that increased maleness with plant size at the flowering stage may
      represent an adaptive strategy for andromonoecious plants, because male flowers
      promote both male and female fertility by increasing pollinator attraction
      without aggravating pollen discounting.

PMID- 18713354
TI  - Phylogenetic analysis of the plant-specific zinc finger-homeobox and mini zinc
      finger gene families.
AB  - Zinc finger-homeodomain proteins (ZHD) are present in many plants; however, the
      evolutionary history of the ZHD gene family remains largely unknown. We show here
      that ZHD genes are plant-specific, nearly all intronless, and related to MINI
      ZINC FINGER (MIF) genes that possess only the zinc finger. Phylogenetic analyses
      of ZHD genes from representative land plants suggest that non-seed plant ZHD
      genes occupy basal positions and angiosperm homologs form seven distinct clades.
      Several clades contain genes from two or more major angiosperm groups, including
      eudicots, monocots, magnoliids, and other basal angiosperms, indicating that
      several duplications occurred before the diversification of flowering plants. In
      addition, specific lineages have experienced more recent duplications. Unlike the
      ZHD genes, MIFs are found only from seed plants, possibly derived from ZHDs by
      loss of the homeodomain before the divergence of seed plants. Moreover, the MIF
      genes have also undergone relatively recent gene duplications. Finally, genome
      duplication might have contributed substantially to the expansion of family size
      in angiosperms and caused a high level of functional redundancy/overlap in these
      genes.

PMID- 18713355
TI  - Monoclonal antibody-based enzyme linked immunosorbent assay for the analysis of
      jasmonates in plants.
AB  - Methyl jasmonate (MeJA) and its free-acid form, jasmonic acid (JA) are naturally
      occurring plant growth regulators widely distributed in higher plants. In order
      to improve the sensitivity for the analysis of MeJA at low levels in small
      amounts of plant samples, a monoclonal antibody (MAb) (designated as MAb
      3E(5)D(7)C(4)B(6)) against MeJA was derived from a JA-bovine serum albumin (BSA)
      conjugate as an immunogen. The antibody belongs to the IgG(1) subclass with a
      kappa type light chain and has a dissociation constant of approximately 6.07 x
      10(-9) M. MAb3E(5)D(7)C(4)B(6) is very specific to MeJA. It was used to develop a
      direct competitive enzyme-linked immunosorbent assay (dcELISA), conventional and
      simplified indirect competitive ELISAs (icELISA). JA was derivatized into MeJA
      for the ELISA analysis. The IC(50) value and detection range for MeJA were,
      respectively, 34 and 4-257 ng/mL by the conventional icELISA, 21 and 3-226 ng/mL
      by the simplified icELISA and 5.0 and 0.7-97.0 ng/mL by the dcELISA. The dcELISA
      was more sensitive than either the conventional or simplified icELISA. The assays
      were used to measure the content of jasmonates as MeJA in tobacco leaves under
      drought stress or inoculated with tobacco mosaic virus and tomato leaves
      inoculated with tomato mosaic virus or Lirioinyza sativae Blanchard as compared
      with the corresponding healthy leaves. The increased jasmonates content indicated
      its role in response to the drought stress and pathogens.

PMID- 18713357
TI  - Water sources of dominant species in three alpine ecosystems on the Tibetan
      Plateau, China.
AB  - Plant water sources were estimated by two or three compartment linear mixing
      models using hydrogen and oxygen isotope (deltaD and delta18O) values of
      different components such as plant xylem water, precipitation and river water as
      well as soil water on the Tibetan Plateau in the summer of 2005. Four dominant
      species (Quercus aquifolioides, Pinus tabulaeformis, Salix rehderiana and
      Nitraria tangutorum) in three typical ecosystems (forest, shrub and desert) were
      investigated in this study. Stable isotope ratios of the summer precipitations
      and the soil water presented variations in spatial and temporal scales. delta18O
      values of N. tangutorum xylem water were constant in the whole growth season and
      very similar to those of deep soil water. Water sources for all of the plants
      came from both precipitations and soil water. Plants switched rapidly among
      different water sources when environmental water conditions changed. Rainwater
      had different contributions to the plants, which was influenced by amounts of
      precipitation. The percentage of plant xylem water derived from rainwater rose
      with an increase in precipitation. Water sources for broad-leaved and coniferous
      species were different although they grew in the same environmental conditions.
      For example, the broad-leaved species Q. aquifolioides used mainly the water from
      deep soil, while 92.5% of xylem water of the coniferous species P. tabulaeformis
      was derived from rainwater during the growth season. The study will be helpful
      for us to fully understand responses of species on the Tibetan Plateau to changes
      in precipitation patterns, and to assess accurately changes of vegetation
      distribution in the future.

PMID- 18713358
TI  - Growth and wood/bark properties of Abies faxoniana seedlings as affected by
      elevated CO2.
AB  - Growth and wood and bark properties of Abies faxoniana seedlings after one year's
      exposure to elevated CO2 concentration (ambient + 350 (+/- 25) micromol/mol)
      under two planting densities (28 or 84 plants/m(2)) were investigated in closed
      top chambers. Tree height, stem diameter and cross-sectional area, and total
      biomass were enhanced under elevated CO2 concentration, and reduced under high
      planting density. Most traits of stem bark were improved under elevated CO2
      concentration and reduced under high planting density. Stem wood production was
      significantly increased in volume under elevated CO2 concentration under both
      densities, and the stem wood density decreased under elevated CO2 concentration
      and increased under high planting density. These results suggest that the
      response of stem wood and bark to elevated CO2 concentration is density
      dependent. This may be of great importance in a future CO2 enriched world in
      natural forests where plant density varies considerably. The results also show
      that the bark/wood ratio in diameter, stem cross-sectional area and dry weight
      are not proportionally affected by elevated CO2 concentration under the two
      contrasting planting densities. This indicates that the response magnitude of
      stem bark and stem wood to elevated CO2 concentration are different but their
      response directions are the same.

PMID- 18713359
TI  - Growing season ecosystem respirations and associated component fluxes in two
      alpine meadows on the Tibetan Plateau.
AB  - From 30 June to 24 September in 2003 ecosystem respiration (Re) in two alpine
      meadows on the Tibetan Plateau were measured using static chamber- and gas
      chromatography- (GC) based techniques. Simultaneously, plant removal treatments
      were set to partition Re into plant autotrophic respiration (Ra) and microbial
      heterotrophic respiration (Rh). Results indicated that Re had clear diurnal and
      seasonal variation patterns in both of the meadows. The seasonal variability of
      Re at both meadow sites was caused mainly by changes in Ra, rather than Rh.
      Moreover, at the Kobresia humilis meadow site (K_site), Ra and Rh accounted for
      54% and 46% of Re, respectively. While at the Potentilla fruticosa scrub meadow
      (P_site), the counterparts accounted for 61% and 39%, respectively. T test showed
      that there was significant difference in Re rates between the two meadows (t =
      2.387, P = 0.022). However, no significant difference was found in Rh rates,
      whereas a significant difference was observed in Ra rates between the two
      meadows. Thus, the difference in Re rate between the two meadows was mainly
      attributed to plant autotrophic respirations. During the growing season, the two
      meadows showed relatively low Q10 values, suggesting that Re, especially Rh was
      not sensitive to temperature variation in the growing season. Additionally, Re
      and Rh at the K_site, as well as Rh at the P_site was negatively correlated with
      soil moisture, indicating that soil moisture would also play an important role in
      respirations.

PMID- 18713360
TI  - Relationship between the virtual dynamic thinning line and the self-thinning
      boundary line in simulated plant populations.
AB  - The self-thinning rule defines a straight upper boundary line on log-log scales
      for all possible combinations of mean individual biomass and density in plant
      populations. Recently, the traditional slope of the upper boundary line, -3/2,
      has been challenged by -4/3 which is deduced from some new mechanical theories,
      like the metabolic theory. More experimental or field studies should be carried
      out to identify the more accurate self-thinning exponent. But it's hard to obtain
      the accurate self-thinning exponent by fitting to data points directly because of
      the intrinsic problem of subjectivity in data selection. The virtual dynamic
      thinning line is derived from the competition-density (C-D) effect as the initial
      density tends to be positive infinity, avoiding the data selection process. The
      purpose of this study was to study the relationship between the virtual dynamic
      thinning line and the upper boundary line in simulated plant stands. Our research
      showed that the upper boundary line and the virtual dynamic thinning line were
      both straight lines on log-log scales. The slopes were almost the same value with
      only a very little difference of 0.059, and the intercept of the upper boundary
      line was a little larger than that of the virtual dynamic thinning line. As
      initial size and spatial distribution patterns became more uniform, the virtual
      dynamic thinning line was more similar to the upper boundary line. This implies
      that, given appropriate parameters, the virtual dynamic thinning line may be used
      as the upper boundary line in simulated plant stands.

PMID- 18713361
TI  - Identification of optimal hyperspectral bands for estimation of rice biophysical
      parameters.
AB  - The present study aims to identify the narrow spectral bands that are most
      suitable for characterizing rice biophysical parameters. The data used for this
      study come from ground-level hyperspectral reflectance measurements for five rice
      species at three levels of nitrogen fertilization during the growing period.
      Reflectance was measured in discrete narrow bands between 350 and 2,500 nm.
      Observed rice biophysical parameters included leaf area index (LAI), wet biomass
      and dry biomass. The stepwise regression method was applied to identify the
      optimal bands for rice biophysical parameter estimation. This research indicated
      that combinations of four narrow bands in stepwise regression models explained
      69% to 83% variability for LAI, 56% to 73% for aboveground wet biomass and 70% to
      83% for leaf wet biomass. An overwhelming proportion of rice information was in a
      particular portion of near infrared (NIR) (1,100-1,150 nm), red-edge (700-750
      nm), and a longer portion of green (550-600 nm). These were followed by the
      moisture-sensitive NIR (950-1,000 nm), the intermediate portion of shortwave
      infrared (SWIR) (1 650-1,700 nm), and another portion of NIR (1,000-1,050 nm).

PMID- 18713363
TI  - Screening landraces for additional sources of field resistance to cassava mosaic
      disease and green mite for integration into the cassava improvement program.
AB  - Twelve cassava landraces were evaluated for sources of resistance genes to
      diseases and pests of major economic importance in Africa. The objective was to
      assess their levels of field resistance to mosaic disease (ACMD), bacterial
      blight (CBB), anthracnose (CAD), and green mite (CGM), compared to TMS30572, an
      elite cultivar widely adopted in Africa. Considerable genotypic variation was
      observed among cultivars for resistance to ACMD and CGM but not for CBB and CAD.
      The lowest mean incidence of 12% and severity of 1.8 on a scale of 1-5 for ACMD
      was recorded for Atu, a landrace with farmer acceptable qualities. In comparison,
      the improved cultivar, TMS 30572, had a mean disease incidence of 72% and a
      severity score of 2.8. Another landrace, MS-20 had the lowest CGM damage score
      (2.1) while TMS 30572 emerged as one of the susceptible cultivars with a damage
      score of 3. Additional sources of resistance to ACMD and CGM that may possibly be
      better than the popular improved cultivar, TMS 30572, were identified in this
      study. These could serve as novel sources of additional genes to complement
      existing resources for elite cassava breeding in Africa.

PMID- 18713362
TI  - Growth inhibition occurs independently of cell mortality in tomato (Solanum
      lycopersicum) exposed to high cadmium concentrations.
AB  - In order to analyze the adaptation potential of tomato shoots to a sudden
      increase in Cd concentration, tomato plants (Solanum lycopersicum L. var. Ailsa
      Craig) were exposed under controlled environmental conditions to a high dose of
      this heavy metal (250 microM CdCl2) in nutrient solution for 7 and 14 d. Both
      root and shoot growth was completely inhibited but all plants remained alive
      until the end of the treatment. Cell viability remained unaffected but the
      activity of the mitochondrial alternative pathway was stimulated by Cd stress at
      the expense of the cytochrome pathway. Cadmium concentration was higher in roots
      than in shoots and a decrease in the rate of net Cd translocation was noticed
      during the second week of stress. Cadmium decreased both leaf conductance (g(l))
      and chlorophyll concentration. However, the effect on net CO2 assimilation
      remained limited and soluble sugars accumulated in leaves. Photochemical
      efficiency of PSII (Fv/Fm) was not affected despite a decrease in the number of
      reaction centers and an inhibition of electron transfer to acceptors of PSII. It
      is concluded that tomato shoot may sustain short term exposure to high doses of
      cadmium despite growth inhibition. This property implies several physiological
      strategies linked to both avoidance and tolerance mechanisms.

PMID- 18713364
TI  - Phenotypic characterization, genetic analysis and gene-mapping for a brittle
      mutant in rice.
AB  - Plant mechanical strength is an important agronomic trait of rice. An ethyl
      methane sulfonate (EMS)-induced rice mutant, fragile plant 2 (fp2), showed
      morphological changes and reduced mechanical strength. Genetic analysis indicated
      that the brittle of fp2 was controlled by a recessive gene. The fp2 gene was
      mapped on chromosome 10. Anatomical analyses showed that the fp2 mutation caused
      the reduction of cell length and cell wall thickness, increasing of cell width,
      and the alteration of cell wall structure as well as the vessel elements. The
      consequence was a global alteration in plant morphology. Chemical analyses
      indicated that the contents of cellulose and lignin decreased, and hemicelluloses
      and silicon increased in fp2. These results were different from the other mutants
      reported in rice. Thus, fp2 might affect the deposition and patterning of
      microfibrils, the biosynthesis and deposition of cell wall components, which
      influences the formation of primary and secondary cell walls, the thickness of
      cell walls, cell elongation and expansion, plant morphology and plant strength in
      rice.

PMID- 18713365
TI  - Isolation and molecular characterization of high molecular weight glutenin
      subunit genes 1Bx13 and 1By16 from hexaploid wheat.
AB  - The high molecular weight glutenin subunit (HMW-GS) pair 1Bx13 + 1By16are
      recognized to positively correlate with bread-making quality; however, their
      molecular data remain unknown. In order to reveal the mechanism by which 1By16
      and 1Bx13 creates high quality, their open reading frames (ORFs) were amplified
      from common wheat Atlas66 and Jimai 20 using primers that were designed based on
      published sequences of HMW glutenin genes. The ORF of 1By16 was 2,220 bp, deduced
      into 738 amino acid residues with seven cysteines including 59 hexapeptides and
      22 nanopeptides motifs. The ORF of 1Bx13 was 2,385 bp, deduced into 795 amino
      acid residues with four cysteines including 68 hexapeptides, 25 nanopeptides and
      six tripeptides motifs. We found that 1By16 was the largest y-type HMW glutenin
      gene described to date in common wheat. The 1By16 had 36 amino acid residues
      inserted in the central repetitive domain compared with 1By15. Expression in
      bacteria and western-blot tests confirmed that the sequence cloned was the ORF of
      HMW-GS 1By16, and that 1Bx13 was one of the largest 1Bx genes that have been
      described so far in common wheat, exhibiting a hexapeptide (PGQGQQ) insertion in
      the end of central repetitive domain compared with 1Bx7. A phylogenetic tree
      based on the deduced full-length amino acid sequence alignment of the published
      HMW-GS genes showed that the 1By16 was clustered with Glu-1B-2, and that the
      1Bx13 was clustered with Glu-1B-1 alleles.

PMID- 18713366
TI  - In vitro transient expression system of latex C-serum was used for analysis of
      hevein promoter in response to abscisic acid in Hevea brasiliensis.
AB  - Hevein has been found to be an essential element in coagulation of rubber
      particles in latex of rubber trees. In a previous study, we cloned a 1,241-bp
      fragment of a 5' upstream region of the hevein gene by genome walking. This
      fragment was analyzed by a 5' end nested deletion method in the present study,
      fused with a uidA (gus) gene to produce a series of tested constructs, which were
      transferred into C-serum of latex and the Gus activities were detected. Results
      showed that the fragment from -749 to -292 was sufficient for expression of gus
      gene in latex, and the fragment from -292 to -168 was crucial in response to
      abscisic acid inducement. In a transient transgenic test of rubber leaf with
      particle bombardment, construct Hev749 conferred gus-specific expression in
      veins, in which the latex tubes mainly distributed. This implies that the
      fragment from -749 to -292 was laticiferous-specific.

PMID- 18713367
TI  - Establishment of a multi-color genomic in situ hybridization technique to
      simultaneously discriminate the three interspecific hybrid genomes in gossypium.
AB  - To identify alien chromosomes in recipient progenies and to analyze genome
      components in polyploidy, a genomic in situ hybridization (GISH) technique that
      is suitable for cotton was developed using increased stringency conditions. The
      increased stringency conditions were a combination of the four factors in the
      following optimized state: 100:1 ratio of blocking DNA to probe, 60% formamide
      wash solution, 43 degrees C temperature wash and a 13 min wash. Under these
      specific conditions using gDNA from Gossypium sturtianum (C(1)C(1)) as a probe,
      strong hybridization signals were only observed on chromosomes from the C(1)
      genome in somatic cells of the hybrid F(1) (G. hirsutum x G. sturtianum)
      (A(t)D(t)C(1)). Therefore, GISH was able to discriminate parental chromosomes in
      the hybrid. Further, we developed a multi-color GISH to simultaneously
      discriminate the three genomes of the above hybrid. The results repeatedly
      displayed the three genomes, A(t), D(t), and C(1), and each set of chromosomes
      with a unique color, making them easy to identify. The power of the multi-color
      GISH was proven by analysis of the hexaploid hybrid F(1) (G. hirsutum x G.
      australe) (A(t)A(t)D(t)D(t)G(2)G(2)). We believe that the powerful multi-color
      GISH technique could be applied extensively to analyze the genome component in
      polyploidy and to identify alien chromosomes in the recipient progenies.

PMID- 18713368
TI  - Microsatellite DNA variation of the gametophyte clones isolated from introduced
      Laminaria japonica (Phaeophyta) and L. longissima of China and varieties derived
      from them.
AB  - The variation of 90 Laminaria gametophyte clones representing the introduced
      Laminaria japonica (Group 1) and Laminaria longissima (Group 2), the varieties of
      L. japonica (Group 3) and the varieties derived from interspecific hybrids (Group
      4) was determined with 18 microsatellite markers. The allelic diversity and Nei's
      gene diversity of Group 1 were significantly higher than those of Group 2 (2.9
      vs. 1.8 and 0.414 vs. 0.161, respectively), demonstrating that the variation of
      the introduced L. japonica is richer than that of L. longissima. Both allelic
      diversity and Nei's gene diversity of Group 3 were lower than those of Group 1,
      indicating that only a portion of variation of L. japonica was incorporated into
      the varieties of L. japonica. Significant genetic differentiation was detected
      between four groups and between female (Population 1) and male (Population 2)
      gametophyte clones in each group. The variation among groups accounted for
      39.95%, while that among populations accounted for 21.65% of the total. The
      genetic distance between Group 1 and Group 4 was obviously longer than that
      between Group 2 and Group 4 (0.686 vs. 0.291), indicating that maternal
      gametophyte clone contributed more variation to the hybrids than the paternal
      gametophyte clone did.

PMID- 18713369
TI  - Behavior of meiotic chromosomes in Pinus wallichiana, P. strobus and their hybrid
      and nrDNA localization in pollen mother cells of the hybrid by using FISH.
AB  - The complete process of meiosis was investigated in Pinus wallichiana, P. strobus
      and their artificial hybrid (F1) using microsporocytes. It is revealed that there
      were slightly lower chiasma frequency, lower ring bivalent frequency, lower
      meiotic index and distinctly higher frequency of aberrance (chromosomal bridges,
      fragments or micronuclei) in pollen mother cells (PMCs) of the hybrid (F1) than
      those of the parental species, which showed a certain degree of differentiation
      between homologous chromosomes of the two parents. However, relatively higher
      frequency of ring bivalents and higher meiotic index in all the three entities
      indicate the great stability of genomes of parental species, and the
      differentiation of genomes between the two parents must have been slight. Total
      nineteen signal loci of 18S rDNA were observed in nine bivalents of the hybrid
      (F1), among which one bivalent bears two loci, while the others have only one. It
      is suggested that distinct differentiation at genetic level existed in homologous
      chromosomes of the two parental species, whereas only slight differentiation at
      karyotypic and genomic levels take place between the parent species.

PMID- 18713370
TI  - Glacial refugia of Ginkgo biloba and human impact on its genetic diversity:
      evidence from chloroplast DNA.
AB  - Variations in the trnK region of chloroplast DNA were investigated in the present
      study using polymerase chain reaction-restriction fragment length polymorphism to
      detect the genetic structure and to infer the possible glacial refugia of Ginkgo
      biloba L. in China. In total, 220 individuals from 12 populations in China and
      three populations outside China were analyzed, representing the largest number of
      populations studied by molecular markers to date. Nineteen haplotypes were
      produced and haplotype A was found in all populations. Populations in south
      western China, including WC, JF, PX, and SP, contained 14 of the 19 haplotypes
      and their genetic diversity ranged from 0.771 4 to 0.867 6. The TM population
      from China also showed a high genetic diversity (H = 0.848 5). Most of the
      genetic variation existed within populations and the differentiation among
      populations was low (G(ST) = 0.2). According to haplotype distribution and the
      historical record, we suggest that populations of G. biloba have been subjected
      to extensive human impact, which has compounded our attempt to infer glacial
      refugia for Ginkgo. Nevertheless, the present results suggest that the center of
      genetic diversity of Ginkgo is mainly in south-western China and in situ
      conservation is needed to protect and preserve the genetic resources.

PMID- 18713371
TI  - High-throughput procedure for single pollen grain collection and polymerase chain
      reaction in plants.
AB  - Single pollen grain polymerase chain reaction (PCR) has succeeded in several
      species, however only limited numbers of pollen grains were involved due to
      difficulties in pollen isolation and lysis. This has limited its application in
      genetic analysis and mapping studies in plants. A high-throughput (HT) procedure
      for collecting and detecting genetic variation in a large number of individual
      pollen grains by PCR is reported. The HT procedure involved the collection of
      individual pollen grains by a pair of special forceps and the lysis of pollen
      grains in a heated alkali/detergent solution followed by neutralization with a
      tris-ethylenediamine tetraacetic acid (TE) buffer. These resulting template
      solutions yielded PCR reactions involving the 5S ribosomal RNA intergenic
      spacers, randomly amplified polymorphic DNA, and simple sequence repeats markers.
      Using this procedure, one person with experience could collect and process up to
      288 single pollen grain PCR reactions per day. The method worked well on
      sugarcane, corn, Miscanthus spp., snap bean, sorghum, and tomato. The ability to
      collect and conduct PCR on individual pollen grains on a large scale offers a new
      approach to genetic analyses and mapping studies in an easily controllable
      environment with a considerable cost reduction. The method will also
      significantly benefit studies in species that are difficult subjects for
      classical genetic research.

PMID- 18713372
TI  - Assessment of genetic variation within Indian mustard (Brassica juncea) germplasm
      using random amplified polymorphic DNA markers.
AB  - Genetic diversity among 45 Indian mustard (Brassica juncea L.) genotypes
      comprising 37 germplasm collections, five advance breeding lines and three
      improved cultivars was investigated at the DNA level using the random amplified
      polymorphic DNA (RAPD) technique. Fifteen primers used generated a total of 92
      RAPD fragments, of which 81 (88%) were polymorphic. Of these, 13 were unique to
      accession 'Pak85559'. Each primer produced four to nine amplified products with
      an average of 6.13 bands per primer. Based on pairwise comparisons of RAPD
      amplification products, Nei and Li's similarity coefficients were calculated to
      evaluate the relationships among the accessions. Pairwise similarity indices were
      higher among the oilseed accessions and cultivars showing narrow ranges of 0.77
      0.99. An unweighted pair-group method with arithmetic averages cluster analysis
      based on these genetic similarities placed most of the collections and oilseed
      cultivars close to each other, showing a low level of polymorphism between the
      accessions used. However, the clusters formed by oilseed collections and
      cultivars were comparatively distinct from that of advanced breeding lines.
      Genetically, all of the accessions were classified into a few major groups and a
      number of individual accessions. Advanced breeding lines were relatively
      divergent from the rest of the accessions and formed independent clusters.
      Clustering of the accessions did not show any pattern of association between the
      RAPD markers and the collection sites. A low level of genetic variability of
      oilseed mustard was attributed to the selection for similar traits and
      horticultural uses. Perhaps close parentage of these accessions further
      contributed towards their little diversity. The study demonstrated that RAPD is a
      simple and fast technique to compare the genetic relationship and pattern of
      variation among the gene pool of this crop.

PMID- 18713373
TI  - Differential responses of the activities of antioxidant enzymes to thermal
      stresses between two invasive Eupatorium species in China.
AB  - The effect of thermal stress on the antioxidant system was investigated in two
      invasive plants, Eupatorium adenophorum Spreng. and E. odoratum L. The former is
      sensitive to high temperature, whereas the latter is sensitive to low
      temperature. Our aim was to explore the relationship between the response of
      antioxidant enzymes and temperature in the two invasive weeds with different
      distribution patterns in China. Plants were transferred from glasshouse to growth
      chambers at a constant 25 degrees C for 1 week to acclimatize to the environment.
      For the heat treatments, temperature was increased stepwise to 30, 35, 38 and
      finally to 42 degrees C. For the cold treatments, temperature was decreased
      stepwise to 20, 15, 10 and finally to 5 degrees C. Plants were kept in the growth
      chambers for 24 h at each temperature step. In E. adenophorum, the coordinated
      increase of the activities of antioxidant enzymes was effective in protecting the
      plant from the accumulation of active oxygen species (AOS) at low temperature,
      but the activities of catalase (CAT), guaiacol peroxidase (POD), ascorbate
      peroxidase (APX), glutathione reductase (GR), and monodehydroascorbate reductase
      (MDAR) were not accompanied by the increase of superoxide dismutase (SOD) during
      the heat treatments. As a result, the level of lipid peroxidation in E.
      adenophorum was higher under heat stress than under cold stress. In E. odoratum,
      however, the lesser degree of membrane damage, as indicated by low
      monodehydroascorbate content, and the coordinated increase of the oxygen.
      Detoxifying enzymes were observed in heat-treated plants, but the antioxidant
      enzymes were unable to operate in cold stress. This indicates that the plants
      have a higher capacity for scavenging oxygen radicals in heat stress than in cold
      stress. The different responses of antioxidant enzymes may be one of the possible
      mechanisms of the differences in temperature sensitivities of the two plant
      species.

PMID- 18713374
TI  - Distribution and fate of anthropogenic nitrogen in the Calamagrostis angustifolia
      wetland ecosystem of Sanjiang Plain, Northeast China.
AB  - Wetlands are important for the protection of water quality of rivers and lakes,
      especially those adjacent to agricultural landscapes, by intercepting and
      removing nutrients in runoff. In this study, the 15N tracer technique was applied
      to study the distribution and fate of anthropogenic nitrogen (15N-fertilizer) in
      Calamagrostis angustifolia Kom wetland plant-soil microcosms to identify the main
      ecological effects of it. 15NH415NO3 solution (14.93 mg N/L, 20.28 at.%15N) was
      added to each microcosm of the first group, which was approximate to the current
      nitrogen concentration (CNC) of farm drainage, and 29.86 mg N/L 15NH415NO3
      solution was added to another group, which was approximate to the double nitrogen
      concentration (DNC) of farm drainage, while no nitrogen (NN) was added to the
      third group. The results suggest that the input of anthropogenic nitrogen has
      positive effects on the biomass and total nitrogen content of plant, and the
      positive effects will be elevated as the increase of its input amount. The
      increase of 15N-fertilizer can also elevate its amounts and proportions in plant
      nitrogen. Soil nitrogen is still the main source of plant nitrogen, but its
      proportion will be reduced as the increase of 15N-fertilizer. The study of the
      fate of 15N-fertilizer indicates that, in CNC treatment, only a small proportion
      is water-dissolved (0.13 +/- 0.20%), a considerable proportion is soil
      immobilized (17.02 +/- 8.62%), or plant-assimilated (23.70 +/- 0.92%), and most
      is lost by gaseous forms (59.15 +/- 8.35%). While in DNC treatment, about 0.09 +/
      0.15% is water-dissolved, 15.33 +/- 7.46% is soil-immobilized, 23.55 +/- 2.86%
      is plant-assimilated, and 61.01 +/- 5.59% is lost by gaseous forms. The double
      input of anthropogenic nitrogen can not elevate the proportions of plant
      assimilation, soil-immobilization and water-dissolution, but it can enhance the
      gaseous losses.

PMID- 18713375
TI  - Rapid inactivation of chloroplastic ascorbate peroxidase is responsible for
      oxidative modification to Rubisco in tomato (Lycopersicon esculentum) under
      cadmium stress.
AB  - To investigate the sensitive site of antioxidant systems in chloroplast under
      cadmium stress and its consequence on reactive oxygen species production and
      action, the sub-organellar localization of chloroplast superoxide dismutases
      (SOD, EC 1.15.1.1) and ascorbic peroxidase (APX, EC 1.11.1.11) isoenzymes and
      changes of enzymes activities under cadmium stress were investigated in tomato
      seedlings. Two APX isoforms, one thylakoid-bound and one stromal, were detected.
      Cd at 50 microM induced a moderate increase of SOD activities but a rapid
      inactivation of both APX isoenzymes. APX inactivation was mainly related to the
      decrease of ascorbate concentration, as supported by in vitro treatment of
      exogenous ascorbate and APX kinetic properties under Cd stress. H2O2 accumulation
      in chloroplast, as a consequence of APX inactivation, was associated with a 60%
      loss of Rubisco (EC 4.1.1.39) activity, which could be partially accounted for by
      a 10% loss of Rubisco content. Protein oxidation assay found that the Rubisco
      large subunit was the most prominent carbonylated protein; the level of
      carbonylated Rubisco large subunit increased fivefold after Cd exposure. Thiol
      groups in the Rubisco large subunit were oxidized, as indicated by non-reducing
      electrophoresis. Treating crude extract with H2O2 resulted in a similar pattern
      of protein oxidation and thiols oxidation with that observed in Cd-treated
      plants. Our study indicates that APXs in the chloroplast is a highly sensitive
      site of antioxidant systems under Cd stress, and the inactivation of APX could be
      mainly responsible for oxidative modification to Rubisco and subsequent decrease
      in its activity.

PMID- 18713376
TI  - Influence of water stress on endogenous hormone contents and cell damage of maize
      seedlings.
AB  - Phytohormones play critical roles in regulating plant responses to stress. We
      investigated the effects of water stress induced by adding 12% (w/v) polyethylene
      glycol to the root medium on the levels of abscisic acid (ABA), indole-3-acid
      (IAA), zeatin (ZT), and gibberellin(3) (GA(3)) in maize leaves. The results
      suggested that water stress had significant effects on the four hormone levels.
      There was a transient increase in the IAA content during the initial stage of
      adaptation to water stress in maize leaves, but it dropped sharply thereafter in
      response to water stress. ABA content increased dramatically in maize leaves
      after 24 h of exposure to water stress, and then the high levels of ABA were
      maintained to the end. The contents of ZT and GA(3) rapidly declined in maize
      leaves subjected to water stress. The effects of water stress on chlorophyll
      content, electrolyte leakage and malondialdehyde levels in maize leaves were also
      studied. The variation of cell damage was negatively correlated with ZT and GA(3)
      levels in maize leaves under water stress. Thus, we explored the roles of ZT and
      GA(3) on the growth of maize seedlings under water stress by exogenous
      application. It is possible that both ZT and GA(3) were effective in protecting
      maize seedlings from water stress, which would be of great importance for the
      improvement of drought tolerance in maize by genetic manipulation.

PMID- 18713377
TI  - Role of nitric oxide dependence on nitric oxide synthase-like activity in the
      water stress signaling of maize seedling.
AB  - Nitric oxide (NO) has been known as an important signal in plant antioxidative
      defense but its production and roles in water stress are less known. The present
      study investigated whether NO dependence on a NO synthase-like (NOS) activity is
      involved in the signaling of drought-induced protective responses in maize
      seedlings.NOS activity, rate of NO release and drought responses were analyzed
      when NO donor sodium nitroprusside (SNP), NO scavenger c-PTIO (2-(4
      carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) and NOS inhibitor L
      NAME (NG-nitro-L-arginine methyl ester) were applied to both detached maize
      leaves and whole plants. Both NOS activity and the rate of NO release increased
      substantially under dehydration stress. The high NOS activity induced by c-PTIO
      as NO scavenger and NO accumulation inhibited by NOS inhibitor L-NAME in
      dehydration-treated maize seedlings indicated that most NO production under water
      deficit stress may be generated from NOS-like activity. After dehydration stress
      for 3 h, detached maize leaves pretreated with NO donor SNP maintained more water
      content than that of control leaves pretreated with water. This result was
      consistent with the decrease in the transpiration rate of SNP-treated leaves
      subjected to drought treatment for 3 h. Membrane permeability, a cell injury
      index, was lower in SNP-treated maize leaves under dehydration stress for 4 h
      when compared with the control leaves. Also, superoxide dismutase (SOD) activity
      of SNP combined drought treatment maize leaves was higher than that of drought
      treatment alone, indicating that exogenous NO treatment alleviated the water loss
      and oxidative damage of maize leaves under water deficit stress. When c-PTIO as a
      specific NO scavenger was applied, the effects of applied SNP were overridden.
      Treatment with L-NAME on leaves also led to higher membrane permeability, higher
      transpiration rate and lower SOD activities than those of control leaves,
      indicating that NOS-like activity was involved in the antioxidative defense under
      water stress. These results suggested that NO dependence on NOS-like activity
      serves as a signaling component in the induction of protective responses and is
      associated with drought tolerance in maize seedlings.

PMID- 18713378
TI  - Gene structure and expression of the high-affinity nitrate transport system in
      rice roots.
AB  - Rice has a preference for uptake of ammonium over nitrate and can use ammonium-N
      efficiently. Consequently, transporters mediating ammonium uptake have been
      extensively studied, but nitrate transporters have been largely ignored.
      Recently, some reports have shown that rice also has high capacity to acquire
      nitrate from growth medium, so understanding the nitrate transport system in rice
      roots is very important for improving N use efficiency in rice. The present study
      identified four putative NRT2 and two putative NAR2 genes that encode components
      of the high-affinity nitrate transport system (HATS) in the rice (Oryza sativa L.
      subsp. japonica cv. Nipponbare) genome. OsNRT2.1 and OsNRT2.2 share an identical
      coding region sequence, and their deduced proteins are closely related to those
      from mono-cotyledonous plants. The two NAR2 proteins are closely related to those
      from mono-cotyledonous plants as well. However, OsNRT2.3 and OsNRT2.4 are more
      closely related to Arabidopsis NRT2 proteins. Relative quantitative reverse
      transcription-polymerase chain reaction analysis showed that all of the six genes
      were rapidly upregulated and then downregulated in the roots of N-starved rice
      plants after they were re-supplied with 0.2 mM nitrate, but the response to
      nitrate differed among gene members. The results from phylogenetic tree, gene
      structure and expression analysis implied the divergent roles for the individual
      members of the rice NRT2 and NAR2 families. High-affinity nitrate influx rates
      associated with nitrate induction in rice roots were investigated and were found
      to be regulated by external pH. Compared with the nitrate influx rates at pH 6.5,
      alkaline pH (pH 8.0) inhibited nitrate influx, and acidic pH (pH 5.0) enhanced
      the nitrate influx in 1 h nitrate induced roots, but did not significantly affect
      that in 4 to 8 h nitrate induced roots.

PMID- 18713379
TI  - Discrimination of repetitive sequences polymorphism in Secale cereale by genomic
      in situ hybridization-banding.
AB  - Genomic in situ hybridization banding (GISH-banding), a technique slightly
      modified from conventional GISH, was used to probe the Chinese native rye (Secale
      cereale L.) DNA, and enabled us to visualize the individual rye chromosomes and
      create a universal reference karyotype of the S. cereale chromosome 1R to 7R. The
      GISH-banding approach used in the present study was able to discriminate S.
      cereale chromosomes or segments in the wheat (Triticum aestivum L.) background,
      including the Triticale, wheat-rye addition and translocation lines. Moreover,
      the GISH-banding pattern of S. cereale subsp. Afghanicum chromosomes was
      consistent with that of Chinese native rye cv. Jingzhou rye; whereas the GISH
      banding pattern of Secale vavilovii was different from that of S. cereale,
      indicating that GISH-banding can be used to study evolutionary polymorphism in
      species or subspecies of Secale. In addition, the production and application of
      GISH-banding to the study of adenine-thymine-riched heterochromatin is discussed.

PMID- 18713380
TI  - Comparison of responses to Mn deficiency between the UK wheat genotypes Maris
      Butler, Paragon and the Australian wheat genotype C8MM.
AB  - Wheat grown in Mn-deficient soil has been widely observed to produce much reduced
      yields. Breeding for Mn-efficient wheat genotypes adapted to Mn-deficient soils
      would represent a long-term solution for wheat agronomy. To characterize the
      physiological basis of Mn efficiency in wheat genotypes would facilitate the
      breeding programs for producing Mn-efficient wheat. Using a solution culture and
      a soil culture system in the present study, a Mn-efficient UK wheat genotype
      Maris Butler and a Mn-inefficient UK wheat genotype Paragon have been compared
      with a Mn-efficient Australian wheat genotype C8MM in the responses to Mn
      deficiency in order to characterize the Mn efficiency in these wheat genotypes.
      Results showed that in solution culture, Maris Butler grown under Mn deficiency
      had 77% relative dry matter yield of control plants that were grown under Mn
      sufficiency, whereas C8MM and Paragon had 60% and 58% relative dry matter yield
      of their respective controls. Results from the soil culture demonstrated that
      relative dry matter yield remained high for Maris Butler and C8MM (53% and 56%,
      respectively), whereas the value for Paragon dropped to 33%. In terms of dry
      matter yield and photosynthetic efficiency, Maris Butler demonstrated Mn
      efficiency in both solution culture and soil culture, whereas C8MM showed Mn
      efficiency only in soil culture. Results also demonstrated that under Mn-depleted
      supply in soil, plants of C8MM had a significantly higher ability in Mn uptake,
      whereas plants of Maris Butler showed a higher internal Mn use efficiency in
      comparison with plants of Paragon. Results from the present study indicate that
      the ability of C8MM to accumulate higher amounts of Mn is the basis of the
      improved Mn efficiency of this genotype in comparison with Paragon, and in Maris
      Butler there is a higher internal use of Mn expressed as an improved
      photosynthetic efficiency in conferring its Mn efficiency. It is suggested that
      more than one mechanism has arisen in wheat to confer tolerance to Mn deficiency.

PMID- 18713381
TI  - Cell-wall invertases from rice are differentially expressed in Caryopsis during
      the grain filling stage.
AB  - Cell-wall invertase plays an important role in sucrose partitioning between
      source and sink organs in higher plants. To investigate the role of cell-wall
      invertases for seed development in rice (Oryza sativa L.), cDNAs of three
      putative cell-wall invertase genes OsCIN1, OsCIN2 and OsCIN3 were isolated. Semi
      quantitative reverse transcription-polymerase chain reaction analysis revealed
      different expression patterns of the three genes in various rice tissues/organs.
      In developing caryopses, they exhibited similar temporal expression patterns,
      expressed highly at the early and middle grain filling stages and gradually
      declined to low levels afterward. However, the spatial expression patterns of
      them were very different, with OsCIN1 primarily expressed in the caryopsis coat,
      OsCIN2 in embryo and endosperm, and OsCIN3 in embryo. Further RNA in situ
      hybridization analysis revealed that a strong signal of OsCIN2 mRNA was detected
      in the vascular parenchyma surrounding the xylem of the chalazal vein and the
      aleurone layer, whereas OsCIN3 transcript was strongly detected in the vascular
      parenchyma surrounding the phloem of the chalazal vein, cross-cells, the aleurone
      layer and the nucellar tissue. These data indicate that the three cell-wall
      invertase genes play complementary/synergetic roles in assimilate unloading
      during the grain filling stage. In addition, the cell type-specific expression
      patterns of OsCIN3 in source leaf blades and anthers were also investigated, and
      its corresponding physiological roles were discussed.

PMID- 18713382
TI  - PPF1 may suppress plant senescence via activating TFL1 in transgenic Arabidopsis
      plants.
AB  - Senescence, a sequence of biochemical and physiological events, constitutes the
      final stage of development in higher plants and is modulated by a variety of
      environmental factors and internal factors. PPF1 possesses an important
      biological function in plant development by controlling the Ca2+ storage capacity
      within chloroplasts. Here we show that the expression of PPF1 might play a
      pivotal role in negatively regulating plant senescence as revealed by the
      regulation of overexpression and suppression of PPF1 on plant development.
      Moreover, TFL1, a key regulator in the floral repression pathway, was screened
      out as one of the downstream targets for PPF1 in the senescence-signaling
      pathway. Investigation of the senescence-related phenotypes in PPF1(-) tfl1-1 and
      PPF1(+) tfl1-1 double mutants confirmed and further highlighted the relation of
      PPF1 with TFL1 in transgenic plants. The activation of TFL1 expression by PPF1
      defines an important pathway possibly essential for the negative regulation of
      plant senescence in transgenic Arabidopsis.

PMID- 18713383
TI  - Genetic diversity in ex-situ conserved Lens culinaris for botanical descriptors,
      biochemical and molecular markers and identification of landraces from indigenous
      genetic resources of Pakistan.
AB  - Lentil, one of the oldest legumes was investigated for diversity based on
      botanical descriptors, total seed proteins, isozymes and random amplified
      polymorphic DNA (RAPD) markers. About one fourth of accessions were heterogeneous
      for botanical descriptors and a seed protein profile. The germplasm collected
      from the province of Baluchistan revealed the prevalence of indigenous landraces
      as high diversity was observed for all of the techniques. Diversity explored
      through various techniques revealed validity irrespective of the sample size or
      geographic pattern, RAPD being the best choice for investigating both inter- and
      intra-accession variation in lentil. Although all of the techniques were able to
      resolve genetic diversity in lentil, isozymes and seed proteins gave low levels
      of genetic diversity, suggesting that more investigation into isozymes of
      specific proteins is required. RAPD is the best option for determining inter- and
      intra-accession variation, and will be required to extend germplasms and primers
      to continue the study of botanical descriptors.

PMID- 18713384
TI  - Simple sequence repeat genetic linkage maps of A-genome diploid cotton (Gossypium
      arboreum).
AB  - This study introduces the construction of the first intraspecific genetic linkage
      map of the A-genome diploid cotton with newly developed simple sequence repeat
      (SSR) markers using 189 F(2) plants derived from the cross of two Asiatic cotton
      cultivars (Gossypium arboreum L.) Jianglingzhongmian x Zhejiangxiaoshanlushu.
      Polymorphisms between the two parents were detected using 6 092 pairs of SSR
      primers. Two-hundred and sixty-eight pairs of SSR primers with better
      polymorphisms were picked out to analyze the F(2) population. In total, 320
      polymorphic bands were generated and used to construct a linkage map with
      JoinMap3.0. Two-hundred and sixty-seven loci, including three phenotypic traits
      were mapped at a logarithms of odds ratio (LOD) > or = 3.0 on 13 linkage groups.
      The total length of the map was 2 508.71 cM, and the average distance between
      adjacent markers was 9.40 cM. Chromosome assignments were according to the
      association of linkages with our backbone tetraploid specific map using the 89
      similar SSR loci. Comparisons among the 13 suites of orthologous linkage groups
      revealed that the A-genome chromosomes are largely collinear with the A(t) and
      D(t) sub-genome chromosomes. Chromosomes associated with inversions suggested
      that allopolyploidization was accompanied by homologous chromosomal
      rearrangement. The inter-chromosomal duplicated loci supply molecular evidence
      that the A-genome diploid Asiatic cotton is paleopolyploid.

PMID- 18713385
TI  - Effects on genome constitution and novel cell wall formation caused by the
      addition of 5RS rye chromosome to common wheat.
AB  - The cytological instability of common wheat-rye addition lines was investigated
      in the present study. The chromosome numbers of almost all addition lines were
      considerably stable, but those of CS + 5R were very variable. The rye chromosome
      added in this line was found to be much shorter than expected. Fluorescent in
      situ hybridization with 5S rDNA and the centromere-specific probes clearly
      revealed that the short rye chromosome contains only a short arm of chromosome 5R
      (5RS). In this line, chromosome numbers of both 5RS and common wheat were
      changeable. The chromosome numbers ranged from 2n = 36 to 2n = 44 in the cells
      carrying two 5RS, and ranged from 2n = 31 to 2n = 44 in one 5RS cells. In
      addition to the chromosome instability, the multicells wrapped in a sac-like
      structure were frequently observed in the root meristematic tissues of CS + 5RS
      after the enzyme treatment for chromosome preparation. Genomic in situ
      hybridization with rye DNA as a probe showed that all cells in sacs investigated
      were at the interphase stage and contained one or two 5RS chromosomes. An
      electron microscopic analysis revealed that the cells of CS + 5RS, particularly
      in sacs, have abnormal (irregular and curved) cell walls. These results indicate
      that 5RS has (a) specific factor(s) influencing the cell wall development as well
      as the genome stability.

PMID- 18713386
TI  - 2008, a year for plants to celebrate.

PMID- 18713387
TI  - Floristics and plant biogeography in China.
AB  - In 1998, a revolutionary system of angiosperm classification, the Angiosperm
      Phylogeny Group system was published. Meanwhile, another new system of
      classification of angiosperms, the eight-class system was proposed by C. Y. Wu
      and colleagues based on long term work on the flora of China. The Flora
      Reipublicae Popularis Sinicae project was initiated in 1959 and completed by
      2004. It is the largest Flora so far completed in the world, including 31 228
      species of vascular plants, or one-eighth of the global plant diversity. The
      English-language and updated Flora of China (FOC) is an international joint
      effort initiated in 1988 and accelerated in 1998. Up to now, 15 of the 24 volumes
      of the FOC have been published. Based on the floristic data, the composition,
      characteristics, floristic divisions and affinities of the flora of China have
      been studied by Wu and colleagues since 1965. In the past 10 years, analyses of
      the available floristic data have been very productive. The East Asiatic
      Floristic Kingdom was proposed in 1998. All 346 families of angiosperms in China,
      according to the eight-class system of classification, were comprehensively
      discussed by using knowledge of current and historical distribution of seed
      plants in the world, together with some morphological and molecular data. A
      scheme of distribution patterns or areal-types of families and genera of seed
      plants in China was modified and elucidated, together with a proposed scheme of
      areal-types of the world. Molecular phylogenetic and biogeographical studies of
      angiosperms in China in the past 10 years also witnessed a progressive
      development. Integration of morphological and molecular data and fossil evidence
      revealed some significant results. Eastern Asia, which used to be regarded as an
      important center of survival during the ice age, is likely an important center of
      diversification of angiosperms.

PMID- 18713388
TI  - Carotenoid metabolism: biosynthesis, regulation, and beyond.
AB  - Carotenoids are indispensable to plants and play a critical role in human
      nutrition and health. Significant progress has been made in our understanding of
      carotenoid metabolism in plants. The biosynthetic pathway has been extensively
      studied. Nearly all the genes encoding the biosynthetic enzymes have been
      isolated and characterized from various organisms. In recent years, there is an
      increasing body of work on the signaling pathways and plastid development, which
      might provide global control of carotenoid biosynthesis and accumulation. Herein,
      we will highlight recent progress on the biosynthesis, regulation, and metabolic
      engineering of carotenoids in plants, as well as the future research towards
      elucidating the regulatory mechanisms and metabolic network that control
      carotenoid metabolism.

PMID- 18713389
TI  - Perspectives in biological nitrogen fixation research.
AB  - Nitrogen fixation, along with photosynthesis is the basis of all life on earth.
      Current understanding suggests that no plant fixes its own nitrogen. Some plants
      (mainly legumes) fix nitrogen via symbiotic anaerobic microorganisms (mainly
      rhizobia). The nature of biological nitrogen fixation is that the dinitrogenase
      catalyzes the reaction-splitting triple-bond inert atmospheric nitrogen (N(2))
      into organic ammonia molecule (NH(3)). All known nitrogenases are found to be
      prokaryotic, multi-complex and normally oxygen liable. Not surprisingly, the
      engineering of autonomous nitrogen-fixing plants would be a long-term effort
      because it requires the assembly of a complex enzyme and provision of anaerobic
      conditions. However, in the light of evolving protein catalysts, the anaerobic
      enzyme has almost certainly been replaced in many reactions by the more efficient
      and irreversible aerobic version that uses O(2). On the other hand, nature has
      shown numerous examples of evolutionary convergence where an enzyme catalyzing a
      highly specific, O(2)-requiring reaction has an oxygen-independent counterpart,
      able to carry out the same reaction under anoxic conditions. In this review, I
      attempt to take the reader on a simplified journey from conventional nitrogenase
      complex to a possible simplified version of a yet to be discovered light
      utilizing nitrogenase.

PMID- 18713390
TI  - Signaling in plant disease resistance and symbiosis.
AB  - Interactions between plants and microbes result in plant disease and symbiosis.
      The former causes considerable economic damage in modern agriculture, while the
      latter has produced great beneficial effects to our agriculture system.
      Comparison of the two interactions has revealed that a common panel of signaling
      pathways might participate in the establishment of the equilibrium between plant
      and microbes or its break-up. Plants appear to detect both pathogenic and
      symbiotic microbes by a similar set of genes. All symbiotic microbes seem to
      produce effectors to overcome plant basal defenses and it is speculated that
      symbiotic effectors have functions similar to pathogenic ones. Signaling
      molecules, salicylic acid (SA), jasmonic acid (JA) and ethylene (ET), are
      involved in both plant defense and symbiosis. Switching off signals contributing
      to deterioration of disease symptom would establish a new equilibrium between
      plant and pathogenic microbes. This would facilitate the development of
      strategies for durable disease resistance.

PMID- 18713391
TI  - Genetic basis of ethylene perception and signal transduction in Arabidopsis.
AB  - Ethylene is a simple gaseous hormone in plants. It plays important roles in plant
      development and stress tolerance. In the presence of ethylene treatment, all
      ethylene receptors are in an activated form, which can physically interact with
      CTR1 and consequently recruit CTR1 protein to endoplasmic reticulum membraneto
      activate it. Activated CTR1 suppresses the downstream signal transduction by an
      unknown mechanism. Upon binding to its receptors, ethylene will inactivate the
      receptor/CTR1 module and in turn alleviate their inhibitory effect on two
      positive regulators acting downstream of CTR1: EIN2 and EIN3. Genetic study
      reveals that EIN2 is an essential component in the ethylene signaling pathway but
      its biochemical function remains a mystery. EIN3 is a plant-specific
      transcription factor and its protein abundance in the nucleus is rapidly induced
      upon ethylene treatment. In the absence of ethylene signal, EIN3 protein is
      degraded by an SCF complex containing one of the two F-box proteins EBF1/EBF2 in
      a 26S proteasome-dependent manner. EIN3 can bind to the promoter sequences of a
      number of downstream components, such as ERFs, which in turn bind to a GCC box, a
      cis-element found in many ethylene-regulated defense genes. Ethylene has been
      shown to also regulate many other hormones' signaling pathways including auxin,
      abscisic acid and jasmonic acid, implying the existence of complicated signaling
      networks in the growth, development and defense responses of various plants.

PMID- 18713392
TI  - Cell fate switch during in vitro plant organogenesis.
AB  - Plant mature cells have the capability to reverse their state of differentiation
      and produce new organs under cultured conditions. Two phases, dedifferentiation
      and redifferentiation, are commonly characterized during in vitro organogenesis.
      In these processes, cells undergo fate switch several times regulated by both
      extrinsic and intrinsic factors, which are associated with reentry to the cell
      cycle, the balance between euchromatin and heterochromatin, reprogramming of gene
      expression, and so forth. This short article reviews the advances in the
      mechanism of organ regeneration from plant somatic cells in molecular, genomic
      and epigenetic aspects, aiming to provide important information on the mechanism
      underlying cell fate switch during in vitro plant organogenesis.

PMID- 18713393
TI  - Evolutionarily conserved DELLA-mediated gibberellin signaling in plants.
AB  - Gibberellins (GAs) play important roles in many essential plant growth and
      development processes. A family of nuclear growth-repressing DELLA proteins is
      the key component in GA signaling. GA perception is mediated by GID1, and the key
      event of GA signaling is the degradation of DELLA proteins via the 26S proteasome
      pathway. DELLA proteins integrating other plant hormones signaling and
      environmental cue modulating plant growth and development have been revealed. GA
      turning on the de-DELLA-repressing system is conserved, and independently
      establishes step-by-step recruitment of GA-stimulated GID1-DELLA interaction and
      DELLA growth-repression functions during land plant evolution. These discoveries
      open new prospects for the understanding of GA action and DELLA-mediated
      signaling in plants.

PMID- 18713394
TI  - Membrane transporters for nitrogen, phosphate and potassium uptake in plants.
AB  - Nitrogen, phosphorous and potassium are essential nutrients for plant growth and
      development. However, their contents in soils are limited so that crop production
      needs to invest a lot for fertilizer supply. To explore the genetic
      potentialities of crops (or plants) for their nutrient utilization efficiency has
      been an important research task for many years. In fact, a number of evidences
      have revealed that plants, during their evolution, have developed many
      morphological, physiological, biochemical and molecular adaptation mechanisms for
      acquiring nitrate, phosphate and potassium under stress conditions. Recent
      discoveries of many transporters and channels for nitrate, phosphate and
      potassium uptake have opened up opportunities to study the molecular regulatory
      mechanisms for acquisition of these nutrients. This review aims to briefly
      discuss the genes and gene families for these transporters and channels. In
      addition, the functions and regulation of some important transporters and
      channels are particularly emphasized.

PMID- 18713395
TI  - Signaling components involved in plant responses to phosphate starvation.
AB  - Phosphorus is one of the macronutrients essential for plant growth and
      development. Many soils around the world are deficient in phosphate (Pi) which is
      the form of phosphorus that plants can absorb and utilize. To cope with the
      stress of Pi starvation, plants have evolved many elaborate strategies to enhance
      the acquisition and utilization of Pi from the environment. These strategies
      include morphological, biochemical and physiological responses which ultimately
      enable plants to better survive under low Pi conditions. Though these adaptive
      responses have been well described because of their ecological and agricultural
      importance, our studies on the molecular mechanisms underlying these responses
      are still in their infancy. In the last decade, significant progresses have been
      made towards the identification of the molecular components which are involved in
      the control of plant responses to Pi starvation. In this article, we first
      provide an overview of some major responses of plants to Pi starvation, then
      summarize what we have known so far about the signaling components involved in
      these responses, as well as the roles of sugar and phytohormones.

PMID- 18713396
TI  - Sexual reproduction in higher plants I: fertilization and the initiation of
      zygotic program.
AB  - Sexual plant reproduction is a critical developmental step in the life cycle of
      higher plants, to allow maternal and paternal genes to be transmitted in a highly
      regulated manner to the next generation. During evolution, a whole set of signal
      transduction machinery is developed by plants to ensure an error-free recognition
      between male and female gametes and initiation of zygotic program. In the past
      few years, the molecular machineries underlying this biological process have been
      elucidated, particularly on the importance of synergid cells in pollen tube
      guidance, the Ca(++) spike as the immediate response of fertilization and the
      epigenetic regulation of parental gene expressions in early zygotic
      embryogenesis. This review outlines the most recent development in this area.

PMID- 18713397
TI  - Gamete recognition in higher plants: an abstruse but charming mystery.
AB  - Although much effort has been made to uncover the mechanism underlying double
      fertilization, little knowledge has been acquired for understanding the molecular
      base of gamete recognition, mainly because of technical limitations. Still,
      progress has been made in terms of the mechanism, including the identification of
      candidate molecules that are involved in gamete recognition in angiosperms. New
      cues for gamete recognition have been found by the successful separation of the
      gametes and construction of gamete-specific cDNA libraries in several species,
      and the application of molecular approaches for studying this process by
      mutations. Thus, the topic is considered an abstruse but charming mystery.

PMID- 18713398
TI  - Histone deacetylase genes in Arabidopsis development.
AB  - Histone acetylation and deacetylation are directly connected with transcriptional
      activation and silencing in eukaryotes. Gene families for enzymes that accomplish
      these histone modifications show surprising complexity in domain organization,
      tissue-specific expression, and function. This review is focused on the family of
      histone deacetylases (HDACs) that remove the acetyl group from core histone
      tails, resulting in a "closed" chromatin and transcriptional repression. In
      Arabidopsis, 18 HDAC genes are divided into three different types - RPD3-like, HD
      tuin and sirtuin - with two or more members in each type. The structural feature
      of each HDAC class, the expression profile of each HDAC gene during development
      and functional insights of important family members are summarized here. It is
      clear that HDACs are an important class of global transcriptional regulators that
      play crucial roles in plant development, defense, and adaptation.

PMID- 18713399
TI  - Comparative analysis of JmjC domain-containing proteins reveals the potential
      histone demethylases in Arabidopsis and rice.
AB  - Histone methylation homeostasis is achieved by controlling the balance between
      methylation and demethylation to maintain chromatin function and developmental
      regulation. In animals, a conserved Jumonji C (JmjC) domain was found in a large
      group of histone demethylases. However, it is still unclear whether plants also
      contain the JmjC domain-containing active histone demethylases. Here we performed
      genome-wide screen and phylogenetic analysis of JmjC domain-containing proteins
      in the dicot plant, Arabidopsis, and monocot plant rice, and found 21 and 20 JmjC
      domain-containing, respectively. We also examined the expression of JmjC domain
      containing proteins and compared them to human JmjC counterparts for potential
      enzymatic activity. The spatial expression patterns of the Arabidopsis JmjC
      domain-containing genes revealed that they are all actively transcribed genes.
      These active plant JmjC domain-containing genes could possibly function in
      epigenetic regulation to antagonize the activity of the large number of putative
      SET domain-containing histone methyltransferase activity to dynamically regulate
      histone methylation homeostasis.

PMID- 18713400
TI  - Subcellular localizations of AS1 and AS2 suggest their common and distinct roles
      in plant development.
AB  - During leaf organogenesis, a critical step for normal leaf primordium initiation
      is the repression of the class 1 KNOTTED1-like homeobox (KNOX) genes. After leaf
      primordia are formed, they must establish polarity for normal leaf morphogenesis.
      Recent studies have led to the identification of a number of genes that
      participate in the class 1 KNOX gene repression and/or the leaf polarity
      establishment. ASTMMETRIC LEAVES1 and 2 (AS1 and AS2) are two of these genes,
      which are critical for both of these two processes. As a first step towards
      understanding the molecular genetic basis of the AS1-AS2 action, we determined
      the subcellular localizations of the two proteins in both tobacco BY2 cells and
      Arabidopsis plants, by fusing them to yellow/cyan fluorescent protein (YFP/CFP).
      Our data showed that AS1 and AS2 alone were predominantly localized in the
      nucleolus and the nucleoplasm, respectively. The presence of both AS1 and AS2
      proteins in the same interphase cell demonstrated their co-localization in both
      nucleolus and nucleoplasm. In addition, AS1 alone was able to associate with the
      condensed chromosome in the metaphase cell. Our data suggest that AS1, AS2 and
      the AS1-AS2 protein complex may have distinct functions, which are all required
      for normal plant development.

PMID- 18713401
TI  - SAD2 in Arabidopsis functions in trichome initiation through mediating GL3
      function and regulating GL1, TTG1 and GL2 expression.
AB  - Most genes identified that control Arabidopsis trichome initiation and formation
      are transcription factors or regulatory components in transcriptional networks
      and include GLABROUS1 (GL1), GLABRA2 (GL2), GLABRA3 (GL3) and TRANSPARENT TESTA
      GLABRA1 (TTG1). Herein, we report that an importin beta-like protein, SENSITIVE
      TO ABA AND DROUGHT2 (SAD2), is required for trichome initiation. Mutations in
      SAD2 disrupted trichome initiation resulting in reduced trichome number, but had
      no effect on trichome development or root hair number and development. Expression
      levels of GL1, MYB23, GL2 and TTG1 were reduced in shoots of sad2 mutants while
      expression levels of GL3 and ENHANCER OF GLABRA3 (EGL3) were enhanced.
      Overexpression of GL3 increased trichome numbers in wild type but not in sad2
      mutants, indicating that the function of the GL3 protein is altered in the sad2
      mutants. In contrast, overexpression of GFP-GL1 decreased trichome number in both
      wild type and sad2. Double mutant analysis of gl1 sad2 and gl3 sad2 indicated
      that SAD2 functions genetically, at least in part, in the same pathway with these
      two genes. Co-immunoprecipitation indicated that the sad2 mutation does not
      disrupt formation of the TTG1-GL3-GL1 complex. Analysis of GFP fusions of GL1,
      GL2, GL3 and TTG1 suggested that these proteins are most likely not direct cargo
      of SAD2. Our data suggest that SAD2 is involved in trichome initiation by
      regulating these nuclear genes.

PMID- 18713402
TI  - Novel nuclear protein ALC-INTERACTING PROTEIN1 is expressed in vascular and
      mesocarp cells in Arabidopsis.
AB  - Pod shattering is an agronomical trait that is a result of the coordinated action
      of cell differentiation and separation. In Arabidopsis, pod shattering is
      controlled by a complex genetic network in which ALCATRAZ (ALC), a member of the
      basic helix-loop-helix family, is critical for cell separation during fruit
      dehiscence. Herein, we report the identification of ALC-INTERACTING PROTEIN1
      (ACI1) via the yeast two-hybrid screen. ACI1 encodes a nuclear protein with a
      lysine-rich domain and a C-terminal serine-rich domain. ACI1 is mainly expressed
      in the vascular system throughout the plant and mesocarp of the valve in
      siliques. Our data showed that ACI1 interacts strongly with the N-terminal
      portion of ALC in yeast cells and in plant cells in the nucleus as demonstrated
      by bimolecular fluorescence complementation assay. Both ACI1 and ALC share an
      overlapping expression pattern, suggesting that they likely function together in
      planta. However, no detectable phenotype was found in plants with reduced ACI1
      expression by RNA interference technology, suggesting that ACI1 may be redundant.
      Taken together, these data indicate that ALC may interact with ACI1 and its
      homologs to control cell separation during fruit dehiscence in Arabidopsis.

PMID- 18713403
TI  - Phenotypic plasticity of life history characteristics: quantitative analysis of
      delayed reproduction of green foxtail (Setaria viridis) in the Songnen Plain of
      China.
AB  - Green foxtail (Setaria viridis L.) is a common weed species in temperate regions.
      Research on the effect of delayed reproduction on the phenotypic plasticity and
      regularity of the vegetative and reproductive growth is of vital significance for
      understanding population regulation and control of the weed in the growing
      season. Green foxtail seeds were sown every 10 days from 25 June to 24 August of
      2004. The growth and production metrics were measured via harvesting tufts and
      statistical analysis was carried out. The results showed that the reproductive
      tillers, seed number, seed biomass and one thousand-seed weight of plants at the
      first sowing (25 June) approximately increased 28.8, 7 827.0, 1 104.0 and 12.3
      times compared with that at the last sowing (24 August), respectively. Total
      tillers, reproductive tillers and height increased linearly as the reproductive
      period delayed, however, biomass increased exponentially. Quadratic equations
      best explained the relationships between the delayed reproductive period and seed
      number, inflorescence length, one thousand-seed weight, seed biomass. Based on
      the quantity and quality of seed production, weeding young seedlings emerging
      before July can be the most effective weed-control strategy in the Songnen Plain.

PMID- 18713404
TI  - Equal sex ratios of a marine green alga, Bryopsis plumosa.
AB  - By finding some important culture conditions as below, we succeeded in
      experimentally controlling the whole life history of a dioecious marine green
      alga, Bryopsis plumosa (Hudson) C. Agardh. In this study, we focused on the
      primary and secondary sex ratios (i.e. at inception and maturity) using these
      culture techniques. Gametogenesis was induced by culturing haploid gametophytes
      with Provasoli's enriched seawater (PES) medium under a 14:10 h light:dark cycle
      at 14 degrees C. Formed zygotes grew into diploid sporophytes, which were
      cultured for 3 months with PES medium under a 14:10 h light:nbsp;dark cycle at 18
      degrees C. Then they were transferred into Schreiber medium and cultured under a
      10:14 h light:dark cycle at 22 degrees C. Within 1 week, zoosporogenesis was
      observed. Zoospores were released within a couple of days. Each zoospore soon
      germinated and grew into a unisexual gametophyte. The primary sex ratio was
      examined in gametophytes that originated from a single sporophyte. The secondary
      sex ratio was studied in the field. Both were estimated as 1:1. Synchronized
      meiotic cell divisions might occur during zoosporogenesis dividing each sex
      determining factor evenly among zoospores. Given the equal sex ratio at maturity,
      there seems to be no environmental factor that differentially affects the
      survival of male or female gametophytes in nature.

PMID- 18713405
TI  - Soral crypsis: protective mimicry of a coccid on an Indian fern.
AB  - Herbivory with crypsis is not well documented in ferns. The present record of
      cryptic coloration of coccid Saissetia filicum Boisduval (Homoptera: Coccidae) to
      the sori of a fern species Asplenium nidus L. (Aspleniaceae) is unique. Predatory
      beetles (Jauravia sp., Coleoptera: Coccinellidae) that feed on the coccids, are
      suggested to be selective pressure for the development of the present homopteran
      soral crypsis. A higher rate of effective predation is noticed in the vegetative
      leaves than the fertile leaves. Aggressive ants were found harvesting honeydew
      secretions from the coccids and defending the trophobionts as well as the host
      fern from their natural enemies. In addition, a possible three-way mutualistic
      relationship among the coccids, its host fern and the tending ant is suggested.
      Differential numbers of coccids on vegetative and fertile leaves is correlated
      with their phenol content and degree of predation by beetles. Such coloration
      mimicry by the coccids may enable them to obtain the necessary blend of sorus of
      the host fern needed to evade beetle detection and attack.

PMID- 18713406
TI  - Response of Polygonum viviparum species and community level to long-term
      livestock grazing in alpine shrub meadow in Qinghai-Tibet Plateau.
AB  - Grazing by domestic herbivores is generally recognized as a major ecological
      factor and an important evolutionary force in grasslands. Grazing has both
      extensive and profound effects on individual plants and communities. We
      investigated the response patterns of Polygonum viviparum species and the species
      diversity of an alpine shrub meadow in response to long-term livestock grazing by
      a field manipulative experiment controlling livestock numbers on the Qinghai
      Tibet Plateau in China. Here, we hypothesize that within a range of grazing
      pressure, grazing can alter relative allocation to different plant parts without
      changing total biomass for some plant species if there is life history trade-offs
      between plant traits. The same type of communities exposed to different grazing
      pressures may only alter relative species' abundances or species composition and
      not vary species diversity because plant species differ in resistant capability
      to herbivory. The results show that plant height and biomass of different organs
      differed among grazing treatments but total biomass remained constant. Biomass
      allocation and absolute investments to both reproduction and growth decreased and
      to belowground storage increased with increased grazing pressure, indicating the
      increasing in storage function was attained at a cost of reducing reproduction of
      bulbils and represented an optimal allocation and an adaptive response of the
      species to long-term aboveground damage. Moreover, our results showed multiform
      response types for either species groups or single species along the gradient of
      grazing intensity. Heavy grazing caused a 13.2% increase in species richness.
      There was difference in species composition of about 18%-20% among grazing
      treatment. Shannon-Wiener (H') diversity index and species evenness (E) index did
      not differ among grazing treatments. These results support our hypothesis.

PMID- 18713407
TI  - Is mass-based metabolism rate proportional to surface area in plant leaves? A
      data re-analysis.
AB  - We re-analyzed two large published databases on leaf traits of plant species from
      seven different biomes, and determined the scaling relationship between leaf
      metabolism rate (mass-based photosynthesis capacity, A(mass), and mass-based dark
      respiration, Rd(mass)) and specific leaf area (SLA) across biomes, using a
      standardized major axis (SMA) method. Overall pooled data produced a scaling
      exponent of 1.33 for the relationship between A(mass) and SLA, significantly
      larger than 1.0; and 1.04 between Rd(mass) and SLA. The scaling exponent of the
      relationship between A(mass) and SLA ranged between 1.23 (in tropical forest) and
      1.66 (in alpine biome), and it was significantly larger in alpine (1.66) and
      grass/meadow (1.52) biomes than in tropical forest (1.23) and wetland (1.27). The
      exponent of the relationship between Rd(mass) and SLA, however, was much smaller
      in wetland (1.05) than in temperate forest (1.29) and tropical rainforest (1.65).
      In general, the predicated universal scaling relationship that the mass-based
      metabolism rate should be proportional to surface area in organisms is not
      applicable at the leaf-level in plants. Rather, the large slope difference of the
      relationship between leaf metabolism rate and SLA found among biomes indicates
      that the strength of the selective forces driving the scaling relationship is
      different among the biomes. The result basically suggests the importance of
      increasing SLA to plant carbon gain in stressful environments and to carbon loss
      in favorable habitats, and therefore has an important implication for survival
      strategies of plants in different biomes.

PMID- 18713408
TI  - A confocal technique applicable to studies of cellular pH-related signaling in
      plants.
AB  - pH may act as a crucial signal in both animal and plant cells. It is very
      difficult to monitor pH signals and this has largely hindered progress in the
      investigation of pH signaling, particularly systematic pH signaling. Here, we
      report the development of a confocal technique to monitor leaf apoplastic pH in
      intact plants, which is particularly suitable for the studies on root to shoot
      signaling. A variety of different pH indicators and plant species were tested. It
      was found that different pH indicators, for example, 2',7'-Bis-(2-carboxyethyl)-5
      (and-6)-carboxyfluoresce (BCECF), SNARF-4F 5-(and-6)-carboxylic acid (SNARF) and
      DM-NERF (NERF), were of different properties, and to successfully monitor pH at a
      sub-cellular level, the comparability between the pH indicator and plant species
      must be involved according to their suitable pH range and loading
      characteristics. The loading characteristics of different pH indicators differ
      with different plant species, cell types and their developing stages. No matter
      what methods were adopted, BCECF and SNARF could not be loaded specifically in
      the leaf apoplast in sunflower, tomato, and Comelina communis L. In contrast,
      regardless of the methods adopted, NERF could be loaded efficiently and
      specifically in the leaf apoplast in C. communis, but not in other plants. In C.
      communis, the determination coefficient for in vitro and in situ calibration of
      NERF was very high, which was respectively 0.9951 and 0.9916, and therefore, the
      adoption of NERF together with C. communis could construct an ideal experimental
      system that is suitable for the investigation of pH systematic signaling. Ratio
      image analysis demonstrated that the leaf apoplastic pH was about 5.5 in non
      stressed conditions, and water deficit could trigger an increase in pH by about
      half a pH unit, which is the first evidence to directly indicate that pH is able
      to act as a systematic signal under water deficit conditions.

PMID- 18713409
TI  - Accumulation of zinc, cadmium, and lead in four populations of Sedum alfredii
      growing on lead/zinc mine spoils.
AB  - Sedum alfredii Hance is a newly reported zinc (Zn) and cadmium (Cd)
      hyperaccumulator native to China. In this study, four populations of S. alfredii
      were collected from Yejiwei (YJW), Jinchuantang (JCT) and Qiaokou (QK) lead
      (Pb)/Zn mines located in Hunan Province as well as Quzhou (QZ) Pb/Zn mine located
      in Zhejiang Province for exploring the intraspecies difference of this plant in
      metal accumulation. Although they grew in the Pb/Zn spoils with relatively
      similar levels of Zn, Cd and Pb, remarkable differences among the four
      populations in tissue heavy metal concentrations were observed. The shoot Zn
      concentration of QZ population (11,116 mg/kg) was highest and nearly five times
      higher than that of the JCT population (1930 mg/kg). Furthermore, the shoot Cd
      concentration observed in the QZ population (1090 mg/kg) was also highest and 144
      times higher than that found in the JCT population (7.5 mg/kg). As for Pb
      concentrations in the shoot of different populations, a fourfold difference
      between the highest and the lowest was also found. Such difference on metal
      accumulation was population-specific and may be significantly explained by
      differences in the soil properties such as pH, organic matter (OM), and
      electrical conductivity (EC). Taking biomass and metal concentration in plants
      into consideration, the QZ, YJW and QK populations may have high potential for Zn
      phytoremediation, the QZ population may have the highest potential in Cd
      phytoremediation, and the QK population may be the most useful in Pb
      phytoremediation.

PMID- 18713410
TI  - Two new neo-clerodane diterpenoids from Scutellaria barbata.
AB  - Two new neo-clerodane diterpenoids, 6,7-dibenzoyloxybarbatin C (1, named barbatin
      D) and 6-(2-acetoxy-3-methylbutanoloxy)-7-(2-carbonyl-3-methylbutanoyloxy)
      barbatin C (2, named barbatin E) were isolated from the whole plant of
      Scutellaria barbata D. Don. Their structures were elucidated by spectroscopic
      methods including extensive 1D and 2D NMR analyses. In vitro, compounds 1-2
      showed cytotoxic activities against three human cancer lines, namely, HONE-1
      nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma
      cells, and with IC(50) values in the range of 3.5-6.7 microM.

PMID- 18713411
TI  - Intraspecific variations of phosphorus absorption and remobilization, P forms,
      and their internal buffering in Brassica cultivars exposed to a P-stressed
      environment.
AB  - Translocation of absorbed phosphorus (P) from metabolically inactive sites to
      active sites in plants growing under P deprivation may increase its P utilization
      efficiency (PUE). Acclimation to phosphate (Pi) starvation may be caused by a
      differential storage pool of vacuolar P, its release, and the intensity of re
      translocation of absorbed P as P starvation inducible environmental cues (PSIEC)
      from ambient environment. Biomass assay and three P forms, namely inorganic (Pi),
      organic (Po), and acid-soluble total (Ptas) were estimated in Brassica cultivars
      exposed to 10 d P deprivation in the culture media. Considering that -delta
      Pi/delta t denotes the rate of Pi release, Pi release velocity (RSPi) was
      determined as the tangent to the equations obtained for Pi f(t) at the mean point
      in the period of greatest Pi decrease, whereas the inverse of the RSPi was an
      estimate of the internal Pi buffering capacity (IBCPi). Inter cultivar variations
      in size of the non-metabolic Pi pool, RSPi, re-translocation of Pi from less to
      more active metabolic sites, and preferential Pi source and sink compartments
      were evaluated under P starvation. The cultivar 'Brown Raya' showed the highest
      Pi storage ability under adequate external P supply, and a more intensive release
      than 'Rain Bow' and 'Dunkled' under P stress. Cultivar 'B.S.A' was inferior to
      'Con-1' in its ability to store and use Pi. Roots and upper leaves were the main
      sink of Pi stored in the lower and middle leaves of all cultivars and showed
      lower IBCPi and larger RSPi values than lower and middle leaves. In another
      trial, six cultivars were exposed to P-free nutrition for 29 d after initial
      feeding on optimum nutrition for 15 d. With variable magnitude, all of the
      cultivars re-translocated P from the above ground parts to their roots under P
      starvation, and [P] at 44 d after transplanting was higher in developing leaves
      compared with developed leaves. Under P deprivation, translocation of absorbed P
      from metabolically inactive to active sites may have helped the tolerant
      cultivars to establish a better rooting system, which provided a basis for
      tolerance against P starvation and increased PUE. A better understanding of the
      extent to which changes in the flux of P absorption and re-translocation under
      PSIEC will help to scavenge Pi from bound P reserves and will bring more
      sparingly soluble P into cropping systems and obtain capitalization of P
      reserves.

PMID- 18713412
TI  - Steroids from the roots of Asparagus officinalis and their cytotoxic activity.
AB  - One new (Sarsasapogenin O) and seven known steroids were isolated from the roots
      of Asparagus officinalis L. Their structures were elucidated on the basis of
      spectroscopic analysis, including various 2D-NMR techniques, hydrolysis, and by
      comparison of spectral data of known compounds. These compounds together with
      nine steroids which were previously isolated from this plant, were tested for
      cytotoxic activity. Among them, eight compounds displayed significant
      cytotoxicities against human A2780, HO-8910, Eca-109, MGC-803, CNE, LTEP-a-2, KB
      and mouse L1210 tumor cells.

PMID- 18713413
TI  - Effects of elevated CO2 on growth, carbon assimilation, photosynthate
      accumulation and related enzymes in rice leaves during sink-source transition.
AB  - To study the effects of growing rice (Oryza sativa L.) leaves under the treatment
      of the short-term elevated CO(2) during the period of sink-source transition,
      several physiological processes such as dynamic changes in photosynthesis,
      photosynthate accumulation, enzyme activities (sucrose phosphate synthase (SPS),
      and sucrose synthase (SS)), and their specific gene (sps1 and RSus1) expressions
      in both mature and developing leaf were measured. Rice seedlings with fully
      expanded sixth leaf (marked as the source leaf, L6) were kept in elevated (700
      micromol/mol) and ambient (350 mol/L) CO(2) until the 7th leaf (marked as the
      sink leaf, L7) fully expanded. The results demonstrated that elevated CO(2)
      significantly increased the rate of leaf elongation and biomass accumulation of
      L7 during the treatment without affecting the growth of L6. However, in both
      developing and mature leaves, net photosynthetic assimilation rate (A), all kinds
      of photosynthate contents such as starch, sucrose and hexose, activities of SPS
      and SS and transcript levels of sps1 and RSus1 were significantly increased under
      elevated CO(2) condition. Results suggested that the elevated CO(2) had
      facilitated photosynthate assimilation, and increased photosynthate supplies from
      the source leaf to the sink leaf, which accelerated the growth and sink-source
      transition in new developing sink leaves. The mechanisms of SPS regulation by the
      elevated CO(2) was also discussed.

PMID- 18713414
TI  - Acid phosphatase activity may affect the tuber swelling by partially regulating
      sucrose-mediated sugar resorption in potato.
AB  - APase activity is involved in regulating many physiological and developmental
      events by affecting the resorption process. In this study, we investigate the
      role of APase activity in tuber development in potato. APase activities were
      mainly localized in cytoplasm, gaps among cells and stroma of amyloplasts of
      parenchyma cells at the stage of tuber swelling. AP1, encoding a putative APase,
      was also highly expressed in swelling tubers and a low level of expression was
      observed in elongated stolons and matured tubers. Inhibition of APase activity by
      applying Brefeldin A, an inhibitor of APase production and secretion,
      significantly suppressed the tuber swelling and moderately affected the stolon
      elongation and the tuberization frequency. During tuber development, sucrose
      serves as the main soluble sugar for long-distance transportation and resorption.
      Moreover, inhibition of APase activity by Brefeldin A markedly reduced the
      sucrose content in tubers and further decreased the starch accumulation,
      suggesting that the function of APase in regulating the tuber swelling might be
      at least partially mediated by the sugar resorption. Exogenous sucrose treatments
      further indicate the important role of sucrose-mediated sugar resorption in tuber
      swelling. These results suggest that the APase activity might affect the tuber
      swelling by partially regulating the sucrose-mediated sugar resorption.

PMID- 18713415
TI  - Establishing a gene trap system mediated by T-DNA(GUS) in rice.
AB  - Two plasmids, p13GUS and p13GUS2, were constructed to create a gene trap system
      containing the promoterless beta-glucuronidase (GUS) reporter gene in the T-DNA
      region. Transformation of these two plasmids into the rice variety Zhonghua 11
      (Oryza sativa ssp. japonica cv.), mediated by Agrobacterium tumefaciens, resulted
      in 942 independent transgenic lines. Histochemical GUS assays revealed that 31
      T(0) plants had various patterns of the reporter gene expression, including
      expression in only one tissue, and simultaneously in two or more tissues.
      Hygromycin-resistant (hyg(r)) homozygotes were screened and the copy number of
      the T-DNA inserts was determined in the GUS-positive transgenic plants. The
      flanking sequences of the T-DNA were isolated by inverse-polymerase chain
      reaction and the insert positions on the rice genome of T-DNA were determined by
      a basic local alignment search tool in the GUS-positive transgenic plants
      transformed with plasmid p13GUS. Moreover, calli induced from the seeds of the
      T(1) generation of 911 GUS-negative transgenic lines were subjected to stress and
      hormone treatments. Histochemical GUS assays were carried out on the calli before
      and after treatment. The results revealed that calli from 21 lines displayed
      differential GUS expression after treatment. All of these data demonstrated that
      this trap system is suitable for identifying rice genes, including those that are
      sensitive to induction.

PMID- 18713416
TI  - Assembly of the protoplasm of Codium fragile (Bryopsidales, Chlorophyta) into new
      protoplasts.
AB  - The cell organelles of the coenocytic alga Codium fragile (Sur.) Hariot
      aggregated rapidly and protoplasts were formed when its protoplasm was extruded
      out in seawater. Continuous observation showed that there were long and
      gelatinous threads connecting the cell organelles. The threads contracted, and
      thus the cell organelles aggregated into protoplasmic masses. The enzyme
      digestion experiments and Coomassie Brilliant Blue and Anthrone stainings showed
      that the long and gelatinous threads involved in the formation of the protoplasts
      might include protein and saccharides as structure components. Nile Red staining
      indicated that the protoplast primary envelope was non-lipid at first, and then
      lipid materials integrated into its surface gradually. The fluorescent brightener
      staining indicated that the cell wall did not regenerate in the newly formed
      protoplasts and they all disintegrated within 72 h after formation. Transmission
      electron microscopy of the cell wall of wild C. fragile showed electron-dense
      material embedded in the whole cell wall at regular intervals. The experiments
      indicated that C. fragile would be a suitable model alga for studying the
      formation of protoplasts.

PMID- 18713417
TI  - Root-fed salicylic acid in grape involves the response caused by aboveground high
      temperature.
AB  - In order to investigate the transportation and distribution of salicylic acid
      (SA) from root to aboveground tissues in response to high temperature, the roots
      of grape plant were fed with (14)C-SA before high temperature treatment.
      Radioactivity results showed that progressive increase in SA transportation from
      root to aboveground as compared with the control varied exactly with the heat
      treatment time. Radioactivity results of leaves at different stem heights
      indicated that the increase in SA amount at the top and middle leaves during the
      early period was most significant in comparison with the bottom leaves. The up
      transportation of SA from root to aboveground tissues was dependent on xylem
      rather than phloem. Auto-radiographs of whole grape plants strongly approved the
      conclusions drawn above. Root-derived SA was believed to be a fundamental source
      in response to aboveground high temperature.

PMID- 18713418
TI  - Seed dynamics in relation to gaps in a tropical montane rainforest of Hainan
      Island, South China: (II) seed bank.
AB  - Spatial and temporal patterns of seed bank dynamics in relation to gaps in an old
      growth tropical montane rainforest of Hainan Island, South China, were studied
      over two consecutive years. From June 2001 to June 2003, soil seed bank sampling
      blocks were taken near each of the four sides of each seed trap and immediately
      put into a nursery for observation of seedling emergence dynamics in four seasons
      (each experiment in each season). The abundances of seedlings that emerged from
      seed banks showed the trend of vine functional group (VFG) > shrub functional
      group (SFG) > tree functional group (TFG) > herb functional group (HFG), but the
      trend in species richness of seedlings that emerged from the soil seed banks was
      TFG > VFG > SFG > HFG. The abundances of seedlings that emerged from seed banks
      in the three gap zones showed no significant differences, but significant
      differences did exist for the species richness. The time of sampling or seasons
      of experiments had significant influences on both the species richness and
      seedling abundances. The seedling emergence processes of each experiment all
      revealed the unimodal patterns. Few emergences occurred 1 year after each
      experiment. Compared with those under closed canopies, the recruitment rates from
      seed to seedlings and from seedlings to saplings in gaps were higher, but the
      mortality rates from saplings to big trees were also higher in the gaps.

PMID- 18713420
TI  - Modeling size-number distributions of seeds for use in soil bank studies.
AB  - Knowledge of soil seed banks is essential to understand the dynamics of plant
      populations and communities and would greatly benefit from the integration of
      existing knowledge on ecological correlations of seed size and shape. The present
      study aims to establish a feasible and meaningful method to describe size-number
      distributions of seeds in multi-species situations. For that purpose, size-number
      distributions of seeds with known length, width and thickness were determined by
      sequential sieving. The most appropriate combination of sieves and seeds
      dimensions was established, and the adequacy of the power function and the
      Weibull model to describe size-number distributions of spherical, non-spherical,
      and all seeds was investigated. We found that the geometric mean of seed length,
      width and thickness was the most adequate size estimator, providing shape
      independent measures of seeds volume directly related to sieves mesh side, and
      that both the power function and the Weibull model provide high quality
      descriptions of size-number distributions of spherical, non-spherical, and all
      seeds. We also found that, in spite of its slightly lower accuracy, the power
      function is, at this stage, a more trustworthy model to characterize size-number
      distributions of seeds in soil banks because in some Weibull equations the
      estimates of the scale parameter were not acceptable.

PMID- 18713419
TI  - Invasion possibility and potential effects of Rhus typhina on Beijing
      municipality.
AB  - Rhus typhina, an alien species introduced from North America, was identified as a
      main afforestation species in Beijing municipality. However, its invasiveness is
      still at odds. To clarify this problem, we applied the North American Screening
      System and the Australian Screening System to preliminarily predict its invasion
      possibility. Both screening systems gave the same recommendation to "reject". The
      geographical distribution was surveyed, with the population features of R.
      typhina against the native plant communities being assessed. With anthropogenic
      assistance, R. typhina has been scattered on almost all habitats from downtown to
      mountains, including roadsides, farmlands and protected areas. As a clonal shrub,
      R. typhina possessed a high spreading rate, varying from 6.3 m/3 years at sterile
      habitats to 6.7 m/3 years at fertile ones. Significantly lower species richness,
      individual density and diversity were observed in the R. typhina community than
      those of the native Vitex negundo Linn.var. heterophylla (Franch.) Rehd.
      community at both sterile and fertile habitats. Continual wide plantation of R.
      typhina may further foster its population expansion, which helps the species to
      overcome spatial isolation. The fact that each root fragment can develop into a
      new individual makes R. typhina very difficult to be eradicated once established.
      From a biological point of view, we believe that R. typhina is a plant invader in
      Beijing. We therefore suggest the government should remove the name of R. typhina
      from the main tree species list in afforesting Beijing.

PMID- 18713421
TI  - Age structure and growth of degraded Populus euphratica floodplain forests in
      north-west China and perspectives for their recovery.
AB  - The Populus euphratica floodplain forests along the lower reaches of the Tarim
      River in continental-arid Xinjiang (north-west China) have been declining in
      recent decades as a result of dam constructions and the withdrawal of water from
      the river. Since 2000, controlled flooding has been carried out to counteract
      this process of degradation. However, the consequences of a changing water regime
      for the floodplain ecosystem are not yet sufficiently investigated. In 2004 we
      sampled a total of 150 P. euphratica trees along two transects at the middle and
      lower reaches of the Tarim River to compare the age structure and growth of these
      two tree populations. The anthropogenic drawdown of the groundwater table had no
      effect on the average growth of the trees at the lower reaches. However, tree
      growth abruptly increased after controlled flooding, thus showing distinct signs
      of recovery.

PMID- 18713422
TI  - Spatiotemporal patterns and dynamics of species richness and abundance of woody
      plant functional groups in a tropical forest landscape of Hainan Island, South
      China.
AB  - Tropical forests are among the most species-diverse ecosystems on Earth. Their
      structures and ecological functions are complex to understand. Functional group
      is defined as a group of species that play similar roles in an ecosystem. The
      functional group approach has been regarded as an effective way of linking the
      compositions of complex ecosystems with their ecological functions. To understand
      the variation of functional groups in species-rich ecosystems after disturbance,
      the present study investigated the spatial pattern and temporal dynamics of woody
      plants in a typically fragmented natural forest landscape of Hainan Island in
      South China. The study area was classified into eight landscape types based on
      vegetation type, disturbance manner and the time of recovery. The woody plant
      species were aggregated into seven functional groups based on the growth form,
      successional status and plant size. The results gained from the present study
      showed that all functional groups, except for the emergent and canopy tree
      species, were present in all eight landscape types. Each landscape type had
      different numbers of dominant functional groups. There are similar species
      richness and stem abundance structure among functional groups between mid
      successional clear cut lowland rainforest and old growth tropical coniferous
      forest. This similarity exists in selective logged lowland rainforest and old
      growth lowland rainforest, as well as among landscape types of montane
      rainforest. The functional groups with the same successional status had similar
      patterns of species richness and stem abundance ratios among different landscape
      types. The variation patterns of functional groups along the successional stages
      in terms of species richness and stem abundance among the tropical lowland
      rainforest landscape types were more similar to each other than those in the
      tropical montane rainforest landscape types. This study provides further support
      for the competition-colonization tradeoff and successional niche theory as
      opposed to models of neutrality and ecological equivalence.

PMID- 18713423
TI  - Inhibition of Ageratina adenophora on spore germination and gametophyte
      development of Macrothelypteris torresiana.
AB  - Allelopathy of Ageratina adenophora plays an important role in its invasion.
      However, we have little knowledge of its allelpathic effects on ferns. In Petri
      dish bioassays, the inhibitory potential of aqueous leachates from roots, stems
      and leaves of A. adenophora was studied on the spore germination and gametophyte
      development of Macrothelypteris torresiana. All leachates inhibited the spore
      germination and growth of the first rhizoid of M. torresiana and inhibitory
      effects increased with increasing leachate concentrations. Root leachates proved
      most inhibitory. Gametophyte rhizoids of M. torresiana treated with stem and leaf
      leachates of A. adenophora were erect, which was similar to those of the control.
      However, gametophyte rhizoids of M. torresiana treated with root leachates of A.
      adenophora were erect, but also curving or swollen. Moreover, curving and swollen
      rhizoids increased with increasing concentrations. As time went by, rhizoids
      treated with root leachates were not so curved and the swelling almost
      disappeared. Possible causes are discussed in the present study. The increasing
      concentrations of leaf leachates also delayed the stages of gametophyte
      development. With the treatment of root leachates, the delay was more obvious.
      Thus A. adenophora inhibited the spore germination and gametophyte development of
      M. torresiana and the root leachates were most inhibitory.

PMID- 18713424
TI  - Species-specific response of photosynthesis to burning and nitrogen
      fertilization.
AB  - The present study was conducted to examine photosynthetic characteristics of
      three dominant grass species (Agropyron cristatum, Leymus chinensis, and
      Cleistogenes squarrosa) and their responses to burning and nitrogen fertilization
      in a semiarid grassland in northern China. Photosynthetic rate (P(n)), stomatal
      conductance (g(s)), and water use efficiency (WUE) showed strong temporal
      variability over the growing season. C. squarrosa showed a significantly higher
      P(n) and WUE than A. cristatum and L. chinensis. Burning stimulated P(n) of A.
      cristatum and L. chinensis by 24-59% (P < 0.05) in the early growing season, but
      not during other time periods. Light-saturated photosynthetic rate (P(max)) in A.
      cristatum and the maximum apparent quantum yield (Phi(max)) in A. cristatum and
      L. chinensis were significantly enhanced by burning (16-67%) in both the
      fertilized and unfertilized plots. The main effect of burning on P(n), P(max) and
      Phi(max) was not significant in C. squarrosa. The burning-induced changes in soil
      moisture could explain 51% (P = 0.01) of the burning-induced changes in P(n) of
      the three species. All three species showed positive responses to N fertilization
      in terms of P(n), P(max), and Phi(max). The stimulation of P(n) under N
      fertilization was mainly observed in the early growing season when the soil
      extractable N content was significantly higher in the fertilized plots. The N
      fertilization-induced changes in soil extractable N content could explain 66% (P
      = 0.001) of the changes in P(n) under N fertilization. The photosynthetic
      responses of the three species indicate that burning and N fertilization will
      potentially change the community structure and ecosystem productivity in the
      semiarid grasslands of northern China.

PMID- 18713425
TI  - Pseudohypericin and hyperforin in Hypericum perforatum from Northern Turkey:
      variation among populations, plant parts and phenological stages.
AB  - Hypericum perforatum is a perennial medicinal plant known as "St. John's wort" in
      Western Europe and has been used in the treatment of several diseases for
      centuries. In the present study, morphologic, phenologic and population
      variability in pseudohypericin and hyperforin concentrations among H. perforatum
      populations from Northern Turkey was investigated for the first time. The aerial
      parts of H. perforatum plants representing a total of 30 individuals were
      collected at full flowering from 10 sites of Northern Turkey to search the
      regional variation in the secondary metabolite concentrations. For morphologic
      and phenologic sampling, plants from one site were gathered in five phenological
      stages: vegetative, floral budding, full flowering, fresh fruiting and mature
      fruiting. The plant materials were air-dried at room temperature and subsequently
      assayed for chemical concentrations by high performance liquid chromatography.
      Secondary metabolite concentrations ranged from traces to 2.94 mg/g dry weight
      (DW) for pseudohypericin and traces -6.29 mg/g DW for hyperforin. The differences
      in the secondary metabolite concentrations among populations of H. perforatum
      were found to be significant. The populations varied greatly in hyperforin
      concentrations, whereas they produced a similar amount of pseudohypericin.
      Concentrations of both secondary metabolites in all tissues increased with
      advancing of plant development and higher accumulation levels were reached at
      flowering. Among different tissues, full opened flowers were found to be superior
      to stems, leaves and the other reproductive parts with regard to pseudohypericin
      and hyperforin accumulations. The present findings might be useful to optimize
      the processing methodology of wild-harvested plant material and obtain increased
      concentrations of these secondary metabolites.

PMID- 18713426
TI  - Determination of anthocyanins and exploration of relationship between their
      composition and petal coloration in crape myrtle (Lagerstroemia hybrid).
AB  - Petal coloration and pigment components in 12 American crape myrtle cultivars
      (Lagerstroemia indicaxLagerstroemia fauriei) and five Chinese crape myrtle
      cultivars (L. indica hybrids) were studied. Color was measured by CIEL*a*b* scale
      and anthocyanin composition of crape myrtle was determined using high-performance
      liquid chromatography coupled to photodiode array detection and electrospray
      ionization mass spectrometry. The presence of the previously reported delphinidin
      3-O-glucoside, petunidin 3-O-glucoside and malvidin 3-O-glucoside were confirmed.
      Cyanidin 3-O-glucoside was identified in crape myrtle for the first time. We
      explored the relationship between petal color and anthocyanin contents by
      multiple linear regression analyses. The results indicated that total flavones
      and flavonols were important variables and contributed to blue-enhancing in crape
      myrtle. Based on anthocyanins and co-pigments analysis, flower color breeding in
      crape myrtle towards true-red and blue were discussed.

PMID- 18713427
TI  - Two new triterpenoid saponins from Gymnema sylvestre.
AB  - Two new oleanane-type triterpenoid saponins, gymnemoside-W1 and W2, together with
      seven known compounds were isolated from the leaves of Gymnema sylvestre R. Br.
      By means of spectral and chemical analysis, the structures of the new compounds
      were elucidated as 16 beta-hydroxyl olean-12-en-3-O-[beta-D-glucopyranosyl (1-
      >6)-beta-D-glucopyranosyl]-28-O-beta-D-glucopyranoside(1) and 16 beta,21 beta,28
      trihydroxyl-olean-12-ene-3-O-glucoronopyranoside (2). The EtOH/H(2)O extracts of
      this plant were shown to be able to inhibit glucose absorption in rats.

PMID- 18713428
TI  - Expression of a high mobility group protein isolated from Cucumis sativus affects
      the germination of Arabidopsis thaliana under abiotic stress conditions.
AB  - Although high mobility group B (HMGB) proteins have been identified from a
      variety of plant species, their importance and functional roles in plant
      responses to changing environmental conditions are largely unknown. Here, we
      investigated the functional roles of a CsHMGB isolated from cucumber (Cucumis
      sativus L.) in plant responses to environmental stimuli. Under normal growth
      conditions or when subjected to cold stress, no differences in plant growth were
      found between the wild-type and transgenic Arabidopsis thaliana overexpressing
      CsHMGB. By contrast, the transgenic Arabidopsis plants displayed retarded
      germination compared with the wild-type plants when grown under high salt or
      dehydration stress conditions. Germination of the transgenic plants was delayed
      by the addition of abscisic acid (ABA), implying that CsHMGB affects germination
      through an ABA-dependent way. The expression of CsHMGB had affected only the
      germination stage, and CsHMGB did not affect the seedling growth of the
      transgenic plants under the stress conditions. The transcript levels of several
      germination-responsive genes were modulated by the expression of CsHMGB in
      Arabidopsis. Taken together, these results suggest that ectopic expression of a
      CsHMGB in Arabidopsis modulates the expression of several germination-responsive
      genes, and thereby affects the germination of Arabidopsis plants under different
      stress conditions.

PMID- 18713429
TI  - In vitro selection for Fusarium wilt resistance in Gladiolus.
AB  - Cormels pieces of four Fusarium susceptible Gladiolus cultivars (Friendship,
      Peter Pears, Victor Borge and Novalux) formed friable calli when cultured in
      vitro on Murashige and Skoog basal medium containing various concentrations of
      auxin and cytokinin. The friable calli established cell suspensions. Plantlet
      regeneration was obtained from the control callus, control cell suspension
      derived callus and in vitro selected Fusarium oxysporum Schlecht. resistant cell
      lines of Friendship. The in vitro cormlets showed 85-95% germination after
      breaking dormancy of 8 weeks at 4 degrees C. Cell suspensions of all four
      Gladiolus cultivars were found to be highly sensitive to fusaric acid. Gradual
      increase in fusaric acid concentrations to the cell-suspension cultures decreased
      cell growth considerably. One albino plant was found from the second generation
      of the in vitro selected cell line of Friendship. The albino plant was found to
      be highly susceptible to F. oxysporum. The cormlets of all in vitro selected cell
      lines of Friendship were inoculated with a conidial suspension of the F.
      oxysporum before planting and were also sprayed with the same spore suspension
      for further characterization when the height of plants was about 6 cm. The four
      selected cell lines showed the same response whether or not they were inoculated
      with conidia of the F. oxysporum. Plantlets of all of the selected cell lines
      exhibited significant growth as compared with the control after application of
      conidia of the F. oxysporum.

PMID- 18713430
TI  - Overexpression of sweet pepper glycerol-3-phosphate acyltransferase gene enhanced
      thermotolerance of photosynthetic apparatus in transgenic tobacco.
AB  - In order to investigate the relationship between the lipid composition in
      thylakoid membrane and thermostability of photosynthetic apparatus, tobacco
      transformed with sweet pepper sense glycerol-3-phosphate acyltransferase (GPAT)
      gene were used to analyze the lipid composition in thylakoid membrane, the net
      photosynthetic rate and chlorophyll fluorescence parameters under high
      temperature stress. The results showed that the saturated extent of
      monogalactosyldiacylglycerol (MGDG), sulfoquinovosyldiacylglycerol,
      digalactosyldiacylglycerol and phosphatidylglycerol in thylakoid membrane of
      transgenic tobacco T(1) lines increased generally. Particularly, the saturated
      extent in MGDG increased obviously by 16.2% and 12.0% in T(1)-2 and T(1)-1,
      respectively. With stress temperature elevating, the maximum efficiency of
      photosystem II (PSII) photochemistry (Fv/Fm), actual photochemical efficiency of
      PSII in the light (Phi(PSII)) and net photosynthetic rate (Pn) of the two lines
      and wild type tobacco plants decreased gradually, but those parameters decreased
      much less in transgenic plants. Even though the recovery process appeared
      differently in the donor and acceptor side of PSII in transgenic tobacco compared
      with wild-type plants, the entire capability of PSII recovered faster in
      transgenic tobacco, which was shown in the parameters of PI, Fv/Fm and Phi(PSII),
      as a result, the recovery of Pn was accelerated. Conclusively, we proposed that
      the increase in saturated extent of thylakoid membrane lipids in transgenic
      plants enhanced the stability of photosynthetic apparatus under high temperature
      stress.

PMID- 18713431
TI  - Reproduction diversity of Enteromorpha prolifera.
AB  - Enteromorpha prolifera (Muell.) J. Agardh (Chlorophyta, Ulvophyceae), which is
      distributed widely in the inter-tidal zone of the ocean, is one of the most
      common fouling green algae. However, the present understandings of the life
      history of E. prolifera have been insufficient to explain their seasonal
      abundances. Thus it is essential to investigate how many reproductive strategies
      are likely to contribute to the successful colonization and flourishing of the
      green alga. In the present study the reproduction diversity of E. prolifera was
      observed and studied systematically by culturing chopped tissues. Our results
      showed that there are in total seven pathways of reproduction for E. prolifera
      including sexual, asexual and vegetative reproduction. It was indicated that the
      variety of the reproductive ways and the large quantity of reproductive cells
      produced and released during the reproductive season are the two key factors that
      facilitate colonization of E. prolifera. The reproduction of the alga E.
      prolifera mainly depends on asexual methods. The results presented here
      contribute to increasing our understanding about how the opportunistic macroalgae
      successfully maintain colonization and excessive growth.

PMID- 18713432
TI  - Transcription factor WRKY70 displays important but no indispensable roles in
      jasmonate and salicylic acid signaling.
AB  - The transcription factor WRKY70 was previously reported to be a common component
      in salicylic acid (SA) and jasmonate (JA) mediated signal pathways in
      Arabidopsis. Here, we present that the inactivation of the WRKY70 gene in wrky70
      1 mutant does not alter the responses of both JA and SA, and that wrky70 mutation
      is unable to restore the coi1 mutant in JA responses. However, overexpression of
      WRKY70 reduces JA responses such as expression of JA-induced genes and JA
      inhibitory root growth, and activates expression of SA-inducible PR1. These data
      indicate that the WRKY70 is important but not indispensable for JA and SA
      signaling, and that other regulators may display the redundant role with WRKY70
      in modulation of JA and SA responses in Arabidopsis. Furthermore, we showed that
      JA inhibits expression of WRKY70 and PR1 by both COI1-dependent and COI1
      independent pathways.

PMID- 18713433
TI  - Retraction. Modeling responses of leafy spurge dispersal to control strategies.

PMID- 18713434
TI  - Lead induced changes in the growth and antioxidant metabolism of the lead
      accumulating and non-accumulating ecotypes of Sedum alfredii.
AB  - The phytotoxicity and antioxidative adaptations of lead (Pb) accumulating ecotype
      (AE) and non-accumulating ecotype (NAE) of Sedum alfredii Hance were investigated
      under different Pb treatments involving 0, 0.02 mmol/L Pb, 0.1 mmol/L Pb and 0.1
      mmol/L Pb/0.1 mmol/L ethylenediaminetetraacetic acid (EDTA) for 6 days. With the
      increasing Pb level, the Pb concentration in the shoots of AE plants enhanced
      accordingly, and EDTA supply helped 51% of Pb translocation to shoots of AE
      compared with those treated with 0.1 mmol/L Pb alone. Moreover, the presence of
      EDTA alleviated Pb phytotoxicity through changes in plant biomass, root
      morphology and chlorophyll contents. Lead toxicity induced hydrogen peroxide
      (H2O2) accumulation and lipid peroxidation in both ecotypes of S. alfredii. The
      activities of superoxide dismutase (SOD), guaiacol peroxidase (G-POD), ascorbate
      peroxidase, and dehydroascorbate reductase elevated in both leaves and roots of
      AE as well as in leaves of NAE with the increasing Pb levels, but SOD and G-POD
      declined in roots of NAE. Enhancement in glutathione reductase activity was only
      detected in roots of NAE while a depression in catalase activity was recorded in
      the leaves of NAE. A significant enhancement in glutathione and ascorbic acid
      (AsA)levels occurred in both ecotypes exposed to Pb and Pb/EDTA treatment
      compared with the control, however, the differences between these two treatments
      were insignificant. The dehydroascorbate (DHA) contents in roots of both ecotypes
      were 1.41 to 11.22-fold higher than those in leaves, whereas the ratios of AsA to
      DHA (1.38 to 6.84) in leaves altering more to the reduced AsA form were much
      higher than those in roots. These results suggested that antioxidative enzymes
      and antioxidants play an important role in counteracting Pb stress in S.
      alfredii.

PMID- 18713435
TI  - Reproductive allocation patterns in different density populations of spring
      wheat.
AB  - The effects of increased intraspecific competition on size hierarchies (size
      inequality) and reproductive allocation were investigated in populations of the
      annual plant, spring wheat (Triticum aestivum). A series of densities (100, 300,
      1000, 3000 and 10,000 plants/m(2)) along a gradient of competition intensity were
      designed in this experiment. The results showed that average shoot biomass
      decreased with increased density. Reproductive allocation was negatively
      correlated to Gini coefficient (R(2) = 0.927), which suggested that reproductive
      allocation is inclined to decrease as size inequality increases. These results
      suggest that both vegetative and reproductive structures were significantly
      affected by intensive competition. However, results also indicated that there
      were different relationships between plant size and reproductive allocation
      pattern in different densities. In the lowest density population, lacking
      competition (100 plants/m(2)), individual reproductive allocation was size
      independent but, in high density populations (300, 1000, 3000 and 10,000
      plants/m(2)), where competition occurred, individual reproductive allocation was
      size dependent: the small proportion of larger individuals were winners in
      competition and got higher reproductive allocation (lower marginal reproductive
      allocation; MRA), and the larger proportion of smaller individuals were
      suppressed and got lower reproductive allocation (higher MRA). In conclusion, our
      results support the prediction that elevated intraspecific competition would
      result in higher levels of size inequality and decreased reproductive allocation
      (with a negative relationship between them). However, deeper analysis indicated
      that these frequency- and size-dependent reproductive strategies were not
      evolutionarily stable strategies.

PMID- 18713436
TI  - Pathways and determinants of early spontaneous vegetation succession in degraded
      lowland of South China.
AB  - Continuous and prolonged human disturbances have caused severe degradation of a
      large portion of lowland in South China, and how to restore such degraded
      ecosystems becomes an increasing concern. The process and mechanisms of
      spontaneous succession, which plays an important role in vegetation restoration,
      have not been adequately examined. To identify the pathways of early spontaneous
      vegetation succession, 41 plots representing plant communities abandoned over
      different times were established and investigated. The communities and indicator
      species of the vegetation were classified by analyzing the important values of
      plant species using multivariate analyses. The results indicated that the plant
      species could be classified into nine plant communities representing six
      succession stages. The pathway and species composition also changed in the
      process of succession. We also measured 13 environmental variables of
      microtopography, soil structure and soil nutrition in each plot to examine the
      driving forces of succession and the vegetation-environment relationships. Our
      results showed that the environmental variables changed in diverse directions,
      and that soil bulk density, soil water capacity and soil acidity were the most
      important factors.

PMID- 18713437
TI  - Excessive copper induces the production of reactive oxygen species, which is
      mediated by phospholipase D, nicotinamide adenine dinucleotide phosphate oxidase
      and antioxidant systems.
AB  - Tobacco BY-2 suspension cells were used to study the chemical damage and its
      associated mechanisms caused by Cu2+. Treatment with 100 micromol/L Cu2+
      generated a large amount of H2O2 and thiobarbituric acid-reactive substances
      (TBARS) in cells. Using phospholipase D (PLD) specific inhibitor (1-butanol) or
      phosphatidic acid (PA), we demonstrated that PLD plays an important role in the
      generation of H2O2 and TBARS. Semi-quantitative reverse-transcriptase polymerase
      chain reaction and enzyme activity assays with wild type and nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase-overexpressing BY-2 cells revealed that
      PLD and PA are the key factors leading to NADPH oxidase activation, which is
      responsible for H2O2 and TBARS production induced by Cu2+. Moreover, the content
      of ascorbic acid (AsA), an effective antioxidant, was sharply reduced in BY-2
      cells exposed to excessive Cu2+. Furthermore, a significant downregulation of the
      enzymes of AsA biosynthesis and the antioxidant system was found. This evidence
      suggests that excessive Cu2+-elevated reactive oxygen species (ROS) production is
      caused by upregulated PLD that elevates the activity of NADPH oxidase and its
      collapsed antioxidant systems that scavenges ROS.

PMID- 18713438
TI  - Changes of leaf morphological, anatomical structure and carbon isotope ratio with
      the height of the Wangtian tree (Parashorea chinensis) in Xishuangbanna, China.
AB  - Leaf morphological and anatomical structure and carbon isotope ratio (delta13C)
      change with increasing tree height. To determine how tree height affects leaf
      characteristics, we measured the leaf area, specific leaf mass (ratio of leaf
      mass to leaf area [LMA]), thickness of the total leaf, cuticle, epidermis,
      palisade and sponge mesophyll, stomata traits and delta13C at different heights
      of Parashorea chinensis with methods of light and scanning electron microscopy
      (SEM) and isotope-ratio mass spectrometry. The correlation and stepwise
      regression between tree height and leaf structure traits were carried out with
      SPSS software. The results showed that leaf structures and delta13C differed
      significantly along the tree height gradient. The leaf area, thickness of sponge
      mesophyll and size of stomata decreased with increasing height, whereas the
      thickness of lamina, palisade mesophyll, epidermis, and cuticle, ratios of
      palisade to spongy thickness, density of stomata and vascular bundles, LMA and
      delta13C increased with tree height. Tree height showed a significant
      relationship with all leaf indices and the most significant relationship was with
      epidermis thickness, leaf area, cuticle thickness, delta13C. The delta13C value
      showed a significantly positive relationship with LMA (R = 0.934). Our results
      supported the hypothesis that the leaf structures exhibited more xeromorphic
      characteristics with the increasing gradient of tree height.

PMID- 18713439
TI  - Mapping and quantitative trait loci analysis of verticillium wilt resistance
      genes in cotton.
AB  - Verticillium wilt is one of the most serious constraints to cotton production in
      almost all of the cotton-growing countries. In this study, "XinLuZao1" (XLZ1), a
      susceptible cultivar Gossypium hirsutum L. and "Hai7124" (H7124), a resistant
      line G. barbadense, and their F(2:3) families were used to map and study the
      disease index induced by verticillium wilt. A total of 430 SSR loci were mapped
      into 41 linkage groups; the map spanned 3,745.9 cM and the average distance
      between adjacent loci was 8.71 cM. Four and five quantitative trait loci (QTLs)
      were detected based on the disease index investigated on July 22 and August 24 in
      2004, respectively. These nine QTLs explained 10.63-28.83% of the phenotypic
      variance, six of them were located on the D sub-genome. Two QTLs located in the
      same marker intervals may partly explain the significant correlation of the two
      traits. QTLs explaining large phenotypic variation were identified in this study,
      which may be quite useful in cotton anti-disease breeding.

PMID- 18713440
TI  - Characters of DNA constitution in the rye B chromosome.
AB  - We have used chromosome microdissection and microcloning to construct a DNA
      library of the entire B chromosome (B) of rye. New rye B-specific sequences have
      been screened from this pool, blasted with other sequences and analyzed to
      elucidate the characters of DNA constitution and the possible pathway of the
      origin of the rye B chromosome. We report the discovery of a new sequence that is
      specific to the rye B centromere.

PMID- 18713441
TI  - Effects of temperature on photosynthetic rates in Korean fir (Abies koreana)
      between healthy and dieback population.
AB  - The present study was carried out on natural Korean fir forests (Abies koreana)
      growing in Mount Halla in Jeju Island, Korea (33 degrees 13-36' N and 126 degrees
      12-57' E). Mount Halla is the highest mountain (1,950 m a.s.l.) in South Korea.
      On the Korean fir forests near the top of Mount Halla in Korea, we established
      permanent plots between dieback and healthy population. Each permanent plot
      includes both dieback and relatively healthy Korean fir individuals. Three sites
      in this study showed similar altitude, topographic position, aspects, slope,
      diameter at breast height, average height and ages. Net photosynthetic rates
      (P(N)) on different temperature regimes were evaluated to explain the forest
      dieback phenomenon on Korean fir populations. Light response curves were
      determined on three different temperature regimes: 15 degrees C, 20 degrees C and
      25 degrees C. The irradiance response curve showed higher values in lower air
      temperatures. Generally, irradiance response curves of healthy Korean fir
      populations were higher than the dieback population at all sites.

PMID- 18713442
TI  - Relationships between phosphatidylglycerol molecular species of thylakoid
      membrane lipids and sensitivities to chilling-induced photoinhibition in rice.
AB  - In an attempt to explore the relationships between phosphatidylglycerol (PG)
      molecular species of thylakoid membrane lipids and sensitivities to chilling
      induced photoinhibition, PG molecular species, D1 protein, electron transport
      activities of thylakoid membrane and the potential quantum yield (F(v)/F(m)) in
      rice treated under middle and low photon flux density (PFD) at 11 degrees C were
      analyzed by high performance liquid chromatography, enzyme hydrolysis, gas phase
      chromatography (GC) and so on. Results showed that the major molecular species of
      PGs in rice thylakoid membrane were 18:3/16:0, 18:3/16:1(3t), 18:2/16:0,
      18:2/16:1(3t), 18:1/16:0, 18:1/16:1(3t), 16:0/16:0, 16:0/16:1(3t). There were
      large differences in the contents of unsaturated PG molecular species such as
      18:1 approximately 3/16:0 approximately 16:1(3t) and saturated PG molecular
      species like 16:0/16:0 approximately 16:1(3t) among japonica cv 9516 (j-9516),
      japonica-indica hybrid F1 j-9516/i-SY63 (ji-95SY) and indica cv Shanyou 63 (i
      SY63). J-9516 containing higher contents of unsaturated PG molecular species was
      manifest in stable D1 protein contents under chill and tolerant to chill-induced
      photoinhibition. In contrast to j-9516, i-SY63 with lower contents of unsaturated
      PG molecular species, exhibited unstable D1 protein contents under chill and was
      sensitive to chill-induced photoinhibition. ji-95SY containing middle contents of
      unsaturated PG molecular species between those of j-9516 and i-SY63, exhibited
      mid extent of sensitivity to chill-induced photoinhibition. The losses in D1
      protein also account for the inhibition in electron transport activity of
      thylakoid membrane and the observed decline in F(v)/F(m). The PG molecular
      species that is efficient in raising chilling-resistant capacity were those
      containing unsaturated fatty acids, namely, unsaturated PG molecular species.
      These results implied that the substrate selectivity of the glycerol-3-phosphate
      acyltransferase in chloroplasts towards 16:0 or 18:1 displayed greatly the
      difference between japonica and indica rice. It was possible to enhance the
      capacity of resistance to chilling-induced photoinhibition by improving or
      modifying the GPAT gene.

PMID- 18713443
TI  - Influences of cross pollination on pollen tube growth and fruit set in Zuili
      plums (Prunus salicina).
AB  - Zuili plum (Prunus salicina L.) trees usually set fruit poorly, although they
      produce high quality fruit. To elucidate the causes of the poor fruit set, pollen
      tube growth into pistils and fruit set percentage were investigated after cross-,
      self- and open-pollination. Ovule development in Zuili pistils was also
      investigated. Pollen tube penetration into the ovules via the obturator and
      micropyle was best when Zuili pistils were pollinated by cv. Black Amber (P.
      domestica) pollen grains, although cross-pollinations with Hongxinli and Miili
      (P. salicina) pollen were more effective than self- and open-pollination. The
      fruit set percentage was also highest in pistils pollinated with Black Amber
      pollen grains. Morphological observation of Zuili pistils revealed that the trees
      produce "double pistils", developing two ovaries from a basal pistil, at a rate
      as high as 28%. In such abnormal pistils, most ovules were lacking an embryo sac
      or were entirely degenerated. The percentage of normally developed ovules was
      24.3% and 8.9% in normal and double pistils, respectively. From these results, we
      conclude that the main causes of poor fruit set of Zuili plums are a lack of
      effective cross-pollination and the production of high percentages of double
      pistils in which normally developed ovules are scarcely formed.

PMID- 18713444
TI  - Seasonal variation and correlation with environmental factors of photosynthesis
      and water use efficiency of Juglans regia and Ziziphus jujuba.
AB  - Both the photosynthetic light curves and CO(2) curves of Juglans regia L. and
      Ziziphus jujuba Mill. var. spinosa in three seasons were measured using a LI-6400
      portable photosynthesis system. The maximal net photosynthetic rate (A(max)),
      apparent quantum efficiency(phi), maximal carboxylation rate (V(cmax)) and water
      use efficiency (WUE) of the two species were calculated based on the curves. The
      results showed that A(max) of J. regia reached its maximum at the late-season,
      while the highest values of A(max) of Z. jujuba occurred at the mid-season. The
      A(max) of J. regia was more affected by relative humidity (RH) of the atmosphere,
      while that of Z. jujuba was more affected by the air temperature. Light
      saturation point (LSP) and Light compensation point (LCP) of J. regia had a
      higher correlation with RH of the atmosphere, those of Z. jujuba, however, had a
      higher correlation with air temperature. V(cmax) of both J. regia and Z. jujuba
      had negative correlation with RH of the atmosphere. WUE of J. regia would
      decrease with the rise of the air temperature while that of Z. jujuba increased.
      Thus it could be seen that RH, temperature and soil moisture had main effect on
      photosynthesis and WUE of J. regia and Z. jujuba. Incorporating data on the
      physiological differences among tree species into forest carbon models will
      greatly improve our ability to predict alterations to the forest carbon budgets
      under various environmental scenarios such as global climate change, or with
      differing species composition.

PMID- 18713445
TI  - Role of soybean GmbZIP132 under abscisic acid and salt stresses.
AB  - Plant basic-leucine zipper (bZIP) transcription factors play important roles in
      many biological processes. In the present study, a bZIP gene, GmbZIP132, was
      cloned from soybean and its biological function under abiotic stresses was
      studied. The transcription of GmbZIP132 was induced by drought and high salt
      treatments. Among all of the organs analyzed, its expression was the highest in
      cotytledon and stems. GmbZIP132 could weakly bind to the GCN4-like motif (GLM)
      (5'-GTGAGTCAT-3') in yeast one-hybrid assay. Compared with wild-type (WT)
      Arabidopsis plants, transgenic plants overexpressing GmbZIP132 showed reduced
      abscisic acid sensitivity and increased water loss rate. At the stage of
      germination, transgenic plants were more tolerant to salt treatment than wild
      type plants. The expression of some abiotic stress-related genes, such as rd29B,
      DREB2A, and P5CS, were upregulated in the transgenic plants. These results
      indicated that GmbZIP132 was an abiotic stress-related gene, and its
      overexpression could increase the salt tolerance of transgenic Arabidopsis plants
      during germination, yet no significant difference of tolerance to abiotic
      stresses was found between transgenic and wild type plants at the seedling stage.

PMID- 18713447
TI  - Pollen morphology of Pedicularis sect. Cyathophora, a group endemic to the
      Eastern Himalaya-Hengduan Mountains region.
AB  - Pedicularis sect. Cyathophora is a distinctive group endemic to the eastern
      Himalaya-Hengduan Mountains region. It was regarded as a 'grex' or section and
      included all four general corolla types of Pedicularis. A unique feature of it is
      that the leaf and bract bases are fused together to form a cup-like structure
      around the stem at each node. Pollen morphology of seven species in sect.
      Cyathophora was investigated by scanning electron microscopy (SEM) and light
      microscopy (LM). Two different pollen apertures could be distinguished (i.e.
      trisyncolpate and bisyncolpate) using LM, while examination with SEM made it
      possible to recognize three types of exine ornamentation (i.e. microscabrate,
      microfoveolate and microreticulate). The microfoveolate exine ornamentation was
      found in trisyncolpate pollen grains for the first time. Possible relationships
      between pollen data and the corolla types were discussed. Comparisons of floral
      and phyllotaxy characters of the genus Pedicularis, together with the pollen
      characters of sect. Cyathophora, could help us to better understand the
      evolutionary trends in Pedicularis.

PMID- 18713446
TI  - Nitric oxide reduces hydrogen peroxide accumulation involved in water stress
      induced subcellular anti-oxidant defense in maize plants.
AB  - Nitric oxide (NO) is a bioactive molecule involved in many biological events, and
      has been reported as pro-oxidant as well as anti-oxidant in plants. In the
      present study, the sources of NO production under water stress, the role of NO in
      water stress-induced hydrogen peroxide (H2O2) accumulation and subcellular
      activities of anti-oxidant enzymes in leaves of maize (Zea mays L.) plants were
      investigated. Water stress induced defense increases in the generation of NO in
      maize mesphyll cells and the activity of nitric oxide synthase (NOS) in the
      cytosolic and microsomal fractions of maize leaves. Water stress-induced defense
      increases in the production of NO were blocked by pretreatments with inhibitors
      of NOS and nitrate reductase (NR), suggesting that NO is produced from NOS and NR
      in leaves of maize plants exposed to water stress. Water stress also induced
      increases in the activities of the chloroplastic and cytosolic anti-oxidant
      enzymes superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione
      reductase (GR), and the increases in the activities of anti-oxidant enzymes were
      reduced by pretreatments with inhibitors of NOS and NR. Exogenous NO increases
      the activities of water stress-induced subcellular anti-oxidant enzymes, which
      decreases accumulation of H2O2. Our results suggest that NOS and NR are involved
      in water stress-induced NO production and NOS is the major source of NO. The
      potential ability of NO to scavenge H2O2 is, at least in part, due to the
      induction of a subcellular anti-oxidant defense.

PMID- 18713448
TI  - Pooling overdispersed binomial data to estimate event rate.
AB  - BACKGROUND: The beta-binomial model is one of the methods that can be used to
      validly combine event rates from overdispersed binomial data. Our objective is to
      provide a full description of this method and to update and broaden its
      applications in clinical and public health research. METHODS: We describe the
      statistical theories behind the beta-binomial model and the associated estimation
      methods. We supply information about statistical software that can provide beta
      binomial estimations. Using a published example, we illustrate the application of
      the beta-binomial model when pooling overdispersed binomial data. RESULTS: In an
      example regarding the safety of oral antifungal treatments, we had 41 treatment
      arms with event rates varying from 0% to 13.89%. Using the beta-binomial model,
      we obtained a summary event rate of 3.44% with a standard error of 0.59%. The
      parameters of the beta-binomial model took the values of 1.24 for alpha and 34.73
      for beta. CONCLUSION: The beta-binomial model can provide a robust estimate for
      the summary event rate by pooling overdispersed binomial data from different
      studies. The explanation of the method and the demonstration of its applications
      should help researchers incorporate the beta-binomial method as they aggregate
      probabilities of events from heterogeneous studies.

PMID- 18713449
TI  - Allogeneic endometrial regenerative cells: an "Off the shelf solution" for
      critical limb ischemia?
AB  - Critical limb ischemia (CLI) is an advanced form of peripheral artery disease
      which is responsible for approximately 100,000 amputations per year in the US.
      Trials to date have reported clinical improvement and reduced need for amputation
      in CLI patients receiving autologous bone marrow or mobilized peripheral blood
      stem cells for stimulation of angiogenesis. While such treatments are currently
      entering Phase III trials, practical and scientific pitfalls will limit
      widespread implementation if efficacy is proven. Hurdles to be overcome include:
      a) reduced angiogenic potential of autologous cells in aged patients with
      cardiovascular risk factors; b) invasiveness/adverse effects of bone marrow
      extraction and G-CSF mobilization, respectively; and c) need for on-site cellular
      manipulation. The Endometrial Regenerative Cell (ERC) is a mesenchymal-like stem
      cell derived from the menstrual blood that is believed to be associated with
      endometrial angiogenesis. We discuss the possibility of using allogeneic ERCs as
      an "off the shelf" treatment for CLI based on the following properties: a) High
      levels of growth factors and matrix metalloprotease production; b) Ability to
      inhibits inflammatory responses and lack of immunogenicity; and c) Expandability
      to great quantities without loss of differentiation ability or karyotypic
      abnormalities.

PMID- 18713450
TI  - Progressive joint limitations as the first alarming signs in a boy with short -
      limbed dwarfism: A case report.
AB  - INTRODUCTION: Contracture is a condition of abnormal shortening or shrinkage of a
      muscle, and or a tendon often with persistent flexion or distortion at a joint.
      Careful documentation of the kind of contractures encountered in different
      paediatric disorders is important in distinguishing a specific subtype.
      Achondroplasia has been considered as the most common short-limbed dwarfism
      syndrome, but there are a variety of other syndromes within this category, and
      other types of limb shortening. CASE PRESENTATION: We report on a 5-year-old boy
      of Austrian origin who manifests progressive joint limitations in connection with
      a dysplastic form of short-limbed dwarfism namely chondrodysplasia punctata
      tibial-metacarpal-type. Progressive joint limitations of maximal intensity over
      the hip, and the ankle joints were the main presenting features. CONCLUSION:
      Osteochondrodysplasias involve abnormal bone or cartilage growth leading to
      skeletal maldevelopment, often short-limbed dwarfism. Diagnosis is by physical
      examination, radiographic documentation, and, in some cases, genetic testing. In
      patients with chondrodysplasia punctata, early life radiographic examination is
      fundamental, since resolution of the punctate calcifications leaving abnormal
      epiphyses and flared and irregular metaphyses after age one to three years seems
      to be characteristic.

PMID- 18713451
TI  - The de Morton Mobility Index (DEMMI): an essential health index for an ageing
      world.
AB  - BACKGROUND: Existing instruments for measuring mobility are inadequate for
      accurately assessing older people across the broad spectrum of abilities. Like
      other indices that monitor critical aspects of health such as blood pressure
      tests, a mobility test for all older acute medical patients provides essential
      health data. We have developed and validated an instrument that captures
      essential information about the mobility status of older acute medical patients.
      METHODS: Items suitable for a new mobility instrument were generated from
      existing scales, patient interviews and focus groups with experts. 51 items were
      pilot tested on older acute medical inpatients. An interval-level unidimensional
      mobility measure was constructed using Rasch analysis. The final item set
      required minimal equipment and was quick and simple to administer. The de Morton
      Mobility Index (DEMMI) was validated on an independent sample of older acute
      medical inpatients and its clinimetric properties confirmed. RESULTS: The DEMMI
      is a 15 item unidimensional measure of mobility. Reliability (MDC(90)), validity
      and the minimally clinically important difference (MCID) of the DEMMI were
      consistent across independent samples. The MDC(90) and MCID were 9 and 10 points
      respectively (on the 100 point Rasch converted interval DEMMI scale). CONCLUSION:
      The DEMMI provides clinicians and researchers with a valid interval-level method
      for accurately measuring and monitoring mobility levels of older acute medical
      patients. DEMMI validation studies are underway in other clinical settings and in
      the community. Given the ageing population and the importance of mobility for
      health and community participation, there has never been a greater need for this
      instrument.

PMID- 18713452
TI  - Neonatal tetanus in Turkey; what has changed in the last decade?
AB  - BACKGROUND: Neonatal tetanus (NT) is still considered as one of the major causes
      of neonatal death in many developing countries. The aim of the present study was
      to assess the characteristics of sixty-seven infants with the diagnosis of
      neonatal tetanus followed-up in the Pediatric Infectious Diseases Ward of Dicle
      University Hospital, Diyarbakir, between 1991 and 2006, and to draw attention to
      factors that may contribute (or may have contributed) to the elimination of the
      disease in Diyarbakir. METHODS: The data of sixty-seven infants whose
      epidemiological and clinical findings were compatible with neonatal tetanus were
      reviewed. Patients were stratified into two groups according to whether they
      survived or not to assess the effect of certain factors in the prognosis. Factors
      having a contribution to the higher rate of tetanus among newborn infants were
      discussed. RESULTS: A total of 55 cases of NT had been hospitalized between 1991
      and 1996 whereas only 12 patients admitted in the last decade. All of the infants
      had been delivered at home by untrained traditional birth attendants (TBA), and
      none of the mothers had been immunized with tetanus toxoid during her pregnancy.
      Twenty-eight (41.8%) of the infants died during their follow-up. Lower birth
      weight, younger age at onset of symptoms and at the time admission, the presence
      of opisthotonus, risus sardonicus and were associated with a higher mortality
      rate. CONCLUSION: Although the number of neonatal tetanus cases admitted to our
      clinic in recent years is lower than in the last decade efforts including
      appropriate health education of the masses, ensurement of access to antenatal
      sevices and increasing the rate of tetanus immunization among mothers still
      should be made in our region to achieve the goal of neonatal tetanus elimination.

PMID- 18713453
TI  - AccPbFRET: an ImageJ plugin for semi-automatic, fully corrected analysis of
      acceptor photobleaching FRET images.
AB  - BACKGROUND: The acceptor photobleaching fluorescence resonance energy transfer
      (FRET) method is widely used for monitoring molecular interactions in cells. This
      method of FRET, while among those with the simplest mathematics, is robust, self
      controlled and independent of fluorophore amounts and ratios. RESULTS: AccPbFRET
      is a user-friendly, efficient ImageJ plugin which allows fully corrected, pixel
      wise calculation and detailed, ROI (region of interest)-based analysis of FRET
      efficiencies in microscopic images. Furthermore, automatic registration and semi
      automatic analysis of large image sets is provided, which are not available in
      any existing FRET evaluation software. CONCLUSION: Despite of the widespread
      applicability of the acceptor photobleaching FRET technique, this is the first
      paper where all possible sources of major errors of the measurement and analysis
      are considered, and AccPbFRET is the only program which provides the complete
      suite of corrections--for registering image pairs, for unwanted photobleaching of
      the donor, for cross-talk of the acceptor and/or its photoproduct to the donor
      channel and for partial photobleaching of the acceptor. The program efficiently
      speeds up the analysis of large image sets even for novice users and is freely
      available.

PMID- 18713454
TI  - Cytoplasmic signaling in the control of mitochondrial uproar?
AB  - The concept of a pre-emptive strike as a good means to prevent greater harm may
      be frequently over-stressed in daily life. However, biological systems in a
      homeostatic balance are prepared to withstand a certain degree of hostile fire by
      rather passive means. This also applies to the maintenance of cell survival,
      where a plethora of protective proteins provide safeguard against erroneous
      activation of death pathways. Apart from these mechanisms active processes are
      also essential for the maintenance of cellular homeostasis, commonly referred to
      as survival signaling. Frequently their targets may be mitochondrial, assuring
      organelle integrity, which is essential for continued energy production and
      survival. Transient or permanent failures in these cellular defense strategies
      result in pathophysiological conditions, which manifest themselves e.g. as cancer
      or ischemia/reperfusion-associated organ damage.

PMID- 18713455
TI  - Mental health among children seeking asylum in Denmark--the effect of length of
      stay and number of relocations: a cross-sectional study.
AB  - BACKGROUND: The process of seeking asylum and the related organisational
      conditions in the host country may adversely affect the children's mental health.
      The objective of this study was to examine the mental health of children seeking
      asylum in relation to organisational factors of the asylum system including
      length of stay and number of relocations. METHODS: The population included all
      260 parent-accompanied asylum-seeking children aged 4-16 years living in the
      asylum centres managed by the Danish Red Cross in October-December 2006. Mental
      health was evaluated using the Strengths and Difficulties Questionnaire. School
      teachers evaluated children aged 4-16; and the 11-16-year-olds completed the self
      report version. To assess the association between organisational factors and
      mental health, binary logistic regression analyses were done using backwards
      elimination. We received responses for 246 children equivalent to 95% of the
      study population. RESULTS: Using teachers' reports, we found that children who
      had been asylum-seeking for more than one year in Denmark had an increased risk
      of having mental difficulties (odds ratio 5.5, 95% CI 1.8-16.3); four or more
      relocations in the asylum system were also associated with a higher risk (3.0,
      1.4-6.7). When the self-report data were included, the associations were even
      stronger. CONCLUSION: Protracted stays at asylum centres and multiple relocations
      within the asylum system appear to have an adverse effect on asylum-seeking
      children's mental health. A limit to the duration of the children's stay in the
      asylum system should be ensured. Follow-up studies with inclusion of other
      conditions, such as parental mental health and the children's previous trauma,
      are needed to clarify the influence of the different factors and their
      interactions.

PMID- 18713456
TI  - Pharmacokinetic and metabolic effects of American ginseng (Panax quinquefolius)
      in healthy volunteers receiving the HIV protease inhibitor indinavir.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) use is prevalent among
      HIV-infected patients to reduce the toxicity of antiretroviral therapy. Ginseng
      has been used for treatment of hyperglycemia and insulin resistance, a common
      side effect of some HIV-1 protease inhibitors (PI). However, it is unknown
      whether American ginseng (AG) can reverse insulin resistance induced by the PI
      indinavir (IDV), and whether these two agents interact pharmacologically. We
      evaluated potential pharmacokinetic interactions between IDV and AG, and assessed
      whether AG improves IDV-induced insulin resistance. METHODS: After baseline
      assessment of insulin sensitivity using the insulin clamp technique, healthy
      volunteers received IDV 800 mg q8 h for 3 days and then IDV and AG 1g q8h for 14
      days. IDV pharmacokinetics and insulin sensitivity were assessed before and after
      AG co-administration. RESULTS: There was no difference in the area-under the
      plasma-concentration-time curve after the co-administration of AG, compared to
      IDV alone (n = 13). Although insulin-stimulated glucose disposal per unit of
      insulin (M/I) decreased by an average of 14.8 +/- 5.9% after 3 days of IDV (from
      0.113 +/- 0.012 to 0.096 +/- 0.014 mg/kgFFM/min per muU/ml of insulin, p = 0.03,
      n = 11), M/I remained unchanged after co-administration of IDV and AG.
      CONCLUSION: IDV decreases insulin sensitivity, which is unaltered by AG co
      administration. AG does not significantly affect IDV pharmacokinetics.

PMID- 18713457
TI  - Temporal changes in key maternal and fetal factors affecting birth outcomes: a 32
      year population-based study in an industrial city.
AB  - BACKGROUND: The link between maternal factors and birth outcomes is well
      established. Substantial changes in society and medical care over time have
      influenced women's reproductive choices and health, subsequently affecting birth
      outcomes. The objective of this study was to describe temporal changes in key
      maternal and fetal factors affecting birth outcomes in Newcastle upon Tyne over
      three decades, 1961-1992. METHODS: For these descriptive analyses we used data
      from a population-based birth record database constructed for the historical
      cohort Particulate Matter and Perinatal Events Research (PAMPER) study. The
      PAMPER database was created using details from paper-based hospital delivery and
      neonatal records for all births during 1961-1992 to mothers resident in Newcastle
      (out of a total of 109,086 singleton births, 97,809 hospital births with relevant
      information). In addition to hospital records, we used other sources for data
      collection on births not included in the delivery and neonatal records, for death
      and stillbirth registrations and for validation. RESULTS: The average family size
      decreased mainly due to a decline in the proportion of families with 3 or more
      children. The distribution of mean maternal ages in all and in primiparous women
      was lowest in the mid 1970s, corresponding to a peak in the proportion of teenage
      mothers. The proportion of older mothers declined until the late 1970s (from
      16.5% to 3.4%) followed by a steady increase. Mean birthweight in all and term
      babies gradually increased from the mid 1970s. The increase in the percentage of
      preterm birth paralleled a two-fold increase in the percentage of caesarean
      section among preterm births during the last two decades. The gap between the
      most affluent and the most deprived groups of the population widened over the
      three decades. CONCLUSION: Key maternal and fetal factors affecting birth
      outcomes, such as maternal age, parity, socioeconomic status, birthweight and
      gestational age, changed substantially during the 32-year period, from 1961 to
      1992. The availability of accurate gestational age is extremely important for
      correct interpretation of trends in birthweight.

PMID- 18713458
TI  - Solitary fibrous tumor of the pleura presenting with syncope episodes when
      coughing.
AB  - BACKGROUND: Solitary fibrous tumor of the pleura is a rarely encountered clinical
      entity which may have different clinical pictures. Although the majority of these
      neoplasms have a benign course, the malignant form has also been reported. CASE
      PRESENTATION: We herein describe a case of 72 year-old man with head, facial, and
      thoracic traumas caused by neurally-mediated situational syncope when coughing.
      The diagnostic work-up including chest x-ray, CT and PET, revealed a large
      solitary mass of the left hemithorax. Radical surgical resection of the mass was
      performed through a left lateral thoracotomy and completed with a wedge resection
      of the lingula. Hystological examination of the surgical specimen showed an
      encapsulated mass measuring 12 x 11.5 x 6 cm consistent with a solitary fibrous
      tumor of the pleura. It's surgical removal definitively resolved the neurologic
      manifestations. The patient had no postoperative complications. At two years
      follow-up the patient is free from recurrence and without clinical
      manifestations. CONCLUSION: In our case its resection definitively resolved the
      episodes of situational syncope due, in our opinion, to the large thoracic mass
      compressing the phrenic nerve.

PMID- 18713459
TI  - Carbonization of a radicular cyst using fiber-optic diode laser: a case report.
AB  - A female patient, 51 years old, complaint of painful swelling on the anatomical
      area of the upper left lateral incisor. The diagnosis of radicular cyst was
      confirmed histo-pathologically. Nowadays, radicular cysts may be treated using
      conventional root canal methods or surgical apicectomy. The possible soft-laser
      reaction to radicular cysts after contact application has not been investigated.
      We present an in vitro case of a diagnosed radicular cyst which carbonized after
      contact application of diode laser. The need for future clinical trials will be
      essential to prove the sensitivity of this procedure in humans.

PMID- 18713460
TI  - Population substructure in Finland and Sweden revealed by the use of spatial
      coordinates and a small number of unlinked autosomal SNPs.
AB  - BACKGROUND: Despite several thousands of years of close contacts, there are
      genetic differences between the neighbouring countries of Finland and Sweden.
      Within Finland, signs of an east-west duality have been observed, whereas the
      population structure within Sweden has been suggested to be more subtle. With a
      fine-scale substructure like this, inferring the cluster membership of
      individuals requires a large number of markers. However, some studies have
      suggested that this number could be reduced if the individual spatial coordinates
      are taken into account in the analysis. RESULTS: We genotyped 34 unlinked
      autosomal single nucleotide polymorphisms (SNPs), originally designed for
      zygosity testing, from 2044 samples from Sweden and 657 samples from Finland, and
      30 short tandem repeats (STRs) from 465 Finnish samples. We saw significant
      population structure within Finland but not between the countries or within
      Sweden, and isolation by distance within Finland and between the countries. In
      Sweden, we found a deficit of heterozygotes that we could explain by simulation
      studies to be due to both a small non-random genotyping error and hidden
      substructure caused by immigration. Geneland, a model-based Bayesian clustering
      algorithm, clustered the individuals into groups that corresponded to Sweden and
      Eastern and Western Finland when spatial coordinates were used, whereas in the
      absence of spatial information, only one cluster was inferred. CONCLUSION: We
      show that the power to cluster individuals based on their genetic similarity is
      increased when including information about the spatial coordinates. We also
      demonstrate the importance of estimating the size and effect of genotyping error
      in population genetics in order to strengthen the validity of the results.

PMID- 18713461
TI  - The coevolution of cooperation and dispersal in social groups and its
      implications for the emergence of multicellularity.
AB  - BACKGROUND: Recent work on the complexity of life highlights the roles played by
      evolutionary forces at different levels of individuality. One of the central
      puzzles in explaining transitions in individuality for entities ranging from
      complex cells, to multicellular organisms and societies, is how different
      autonomous units relinquish control over their functions to others in the group.
      In addition to the necessity of reducing conflict over effecting specialized
      tasks, differentiating groups must control the exploitation of the commons, or
      else be out-competed by more fit groups. RESULTS: We propose that two forms of
      conflict - access to resources within groups and representation in germ line -
      may be resolved in tandem through individual and group-level selective effects.
      Specifically, we employ an optimization model to show the conditions under which
      different within-group social behaviors (cooperators producing a public good or
      cheaters exploiting the public good) may be selected to disperse, thereby not
      affecting the commons and functioning as germ line. We find that partial or
      complete dispersal specialization of cheaters is a general outcome. The
      propensity for cheaters to disperse is highest with intermediate benefit:cost
      ratios of cooperative acts and with high relatedness. An examination of a range
      of real biological systems tends to support our theory, although additional study
      is required to provide robust tests. CONCLUSION: We suggest that trait linkage
      between dispersal and cheating should be operative regardless of whether groups
      ever achieve higher levels of individuality, because individual selection will
      always tend to increase exploitation, and stronger group structure will tend to
      increase overall cooperation through kin selected benefits. Cheater
      specialization as dispersers offers simultaneous solutions to the evolution of
      cooperation in social groups and the origin of specialization of germ and soma in
      multicellular organisms.

PMID- 18713463
TI  - Rapidly exploring structural and dynamic properties of signaling networks using
      PathwayOracle.
AB  - BACKGROUND: In systems biology the experimentalist is presented with a selection
      of software for analyzing dynamic properties of signaling networks. These tools
      either assume that the network is in steady-state or require highly parameterized
      models of the network of interest. For biologists interested in assessing how
      signal propagates through a network under specific conditions, the first class of
      methods does not provide sufficiently detailed results and the second class
      requires models which may not be easily and accurately constructed. A tool that
      is able to characterize the dynamics of a signaling network using an
      unparameterized model of the network would allow biologists to quickly obtain
      insights into a signaling network's behavior. RESULTS: We introduce
      PathwayOracle, an integrated suite of software tools for computationally
      inferring and analyzing structural and dynamic properties of a signaling network.
      The feature which differentiates PathwayOracle from other tools is a method that
      can predict the response of a signaling network to various experimental
      conditions and stimuli using only the connectivity of the signaling network. Thus
      signaling models are relatively easy to build. The method allows for tracking
      signal flow in a network and comparison of signal flows under different
      experimental conditions. In addition, PathwayOracle includes tools for the
      enumeration and visualization of coherent and incoherent signaling paths between
      proteins, and for experimental analysis - loading and superimposing experimental
      data, such as microarray intensities, on the network model. CONCLUSION:
      PathwayOracle provides an integrated environment in which both structural and
      dynamic analysis of a signaling network can be quickly conducted and visualized
      along side experimental results. By using the signaling network connectivity,
      analyses and predictions can be performed quickly using relatively easily
      constructed signaling network models. The application has been developed in
      Python and is designed to be easily extensible by groups interested in adding new
      or extending existing features. PathwayOracle is freely available for download
      and use.

PMID- 18713462
TI  - Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas
      and normal brain tissue: class II and IV are hypoexpressed in glioblastomas.
AB  - BACKGROUND: Glioblastoma is the most lethal primary malignant brain tumor.
      Although considerable progress has been made in the treatment of this aggressive
      tumor, the clinical outcome for patients remains poor. Histone deacetylases
      (HDACs) are recognized as promising targets for cancer treatment. In the past
      several years, HDAC inhibitors (HDACis) have been used as radiosensitizers in
      glioblastoma treatment. However, no study has demonstrated the status of global
      HDAC expression in gliomas and its possible correlation to the use of HDACis. The
      purpose of this study was to evaluate and compare mRNA and protein levels of
      class I, II and IV of HDACs in low grade and high grade astrocytomas and normal
      brain tissue and to correlate the findings with the malignancy in astrocytomas.
      METHODS: Forty-three microdissected patient tumor samples were evaluated. The
      histopathologic diagnoses were 20 low-grade gliomas (13 grade I and 7 grade II)
      and 23 high-grade gliomas (5 grade III and 18 glioblastomas). Eleven normal
      cerebral tissue samples were also analyzed (54 total samples analyzed). mRNA
      expression of class I, II, and IV HDACs was studied by quantitative real-time
      polymerase chain reaction and normalized to the housekeeping gene beta
      glucuronidase. Protein levels were evaluated by western blotting. RESULTS: We
      found that mRNA levels of class II and IV HDACs were downregulated in
      glioblastomas compared to low-grade astrocytomas and normal brain tissue (7 in 8
      genes, p < 0.05). The protein levels of class II HDAC9 were also lower in high
      grade astrocytomas than in low-grade astrocytomas and normal brain tissue.
      Additionally, we found that histone H3 (but not histone H4) was more acetylated
      in glioblastomas than normal brain tissue. CONCLUSION: Our study establishes a
      negative correlation between HDAC gene expression and the glioma grade suggesting
      that class II and IV HDACs might play an important role in glioma malignancy.
      Evaluation of histone acetylation levels showed that histone H3 is more
      acetylated in glioblastomas than normal brain tissue confirming the
      downregulation of HDAC mRNA in glioblastomas.

PMID- 18713464
TI  - Evaluating the systemic right ventricle by CMR: the importance of consistent and
      reproducible delineation of the cavity.
AB  - BACKGROUND: The method used to delineate the boundary of the right ventricle
      (RV), relative to the trabeculations and papillary muscles in cardiovascular
      magnetic resonance (CMR) ventricular volume analysis, may matter more when these
      structures are hypertrophied than in individuals with normal cardiovascular
      anatomy. This study aimed to compare two methods of cavity delineation in
      patients with systemic RV. METHODS: Twenty-nine patients (mean age 34.7 +/- 12.4
      years) with a systemic RV (12 with congenitally corrected transposition of the
      great arteries (ccTGA) and 17 with atrially switched (TGA) underwent CMR. We
      compared measurements of systemic RV volumes and function using two analysis
      protocols. The RV trabeculations and papillary muscles were either included in
      the calculated blood volume, the boundary drawn immediately within the apparently
      compacted myocardial layer, or they were manually outlined and excluded. RV
      stroke volume (SV) calculated using each method was compared with corresponding
      left ventricular (LV) SV. Additionally, we compared the differences in analysis
      time, and in intra- and inter-observer variability between the two methods.
      Paired samples t-test was used to test for differences in volumes, function and
      analysis time between the two methods. Differences in intra- and inter-observer
      reproducibility were tested using an extension of the Bland-Altman method.
      RESULTS: The inclusion of trabeculations and papillary muscles in the ventricular
      volume resulted in higher values for systemic RV end diastolic volume (mean
      difference 28.7 +/- 10.6 ml, p < 0.001) and for end systolic volume (mean
      difference 31.0 +/- 11.5 ml, p < 0.001). Values for ejection fraction were
      significantly lower (mean difference -7.4 +/- 3.9%, p < 0.001) if structures were
      included. LV SV did not differ significantly from RV SV for both analysis methods
      (p = NS). Including structures resulted in shorter analysis time (p < 0.001), and
      showed better inter-observer reproducibility for ejection fraction (p < 0.01).
      CONCLUSION: The choice of method for systemic RV cavity delineation significantly
      affected volume measurements, given the CMR acquisition and analysis systems
      used. We recommend delineation outside the trabeculations for routine clinical
      measurements of systemic RV volumes as this approach took less time and gave more
      reproducible measurements.

PMID- 18713465
TI  - Physiological and molecular characterization of aluminum resistance in Medicago
      truncatula.
AB  - BACKGROUND: Aluminum (Al) toxicity is an important factor limiting crop
      production on acid soils. However, little is known about the mechanisms by which
      legumes respond to and resist Al stress. To explore the mechanisms of Al toxicity
      and resistance in legumes, we compared the impact of Al stress in Al-resistant
      and Al-sensitive lines of the model legume, Medicago truncatula Gaertn. RESULTS:
      A screen for Al resistance in 54 M. truncatula accessions identified eight Al
      resistant and eight Al-sensitive lines. Comparisons of hydroponic root growth and
      root tip hematoxylin staining in an Al-resistant line, T32, and an Al-sensitive
      line, S70, provided evidence that an inducible Al exclusion mechanism occurs in
      T32. Transcriptional events associated with the Al resistance response were
      analyzed in T32 and S70 after 12 and 48 h Al treatment using oligonucleotide
      microarrays. Fewer genes were differentially regulated in response to Al in T32
      compared to S70. Expression patterns of oxidative stress-related genes, stress
      response genes and microscopic examination of Al-treated root tips suggested a
      lower degree of Al-induced oxidative damage to T32 root tips compared to S70.
      Furthermore, genes associated with cell death, senescence, and cell wall
      degradation were induced in both lines after 12 h of Al treatment but
      preferentially in S70 after 48 h of Al treatment. A multidrug and toxin efflux
      (MATE) transporter, previously shown to exude citrate in Arabidopsis, showed
      differential expression patterns in T32 and S70. CONCLUSION: Our results
      identified novel genes induced by Al in Al-resistant and sensitive M. truncatula
      lines. In T32, transcription levels of genes related to oxidative stress were
      consistent with reactive oxygen species production, which would be sufficient to
      initiate cell death of Al-accumulating cells thereby contributing to Al exclusion
      and root growth recovery. In contrast, transcriptional levels of oxidative stress
      related genes were consistent with excessive reactive oxygen species accumulation
      in S70 potentially resulting in necrosis and irreversible root growth inhibition.
      In addition, a citrate-exuding MATE transporter could function in Al exclusion
      and/or internal detoxification in T32 based on Al-induced transcript localization
      studies. Together, our findings indicate that multiple responses likely
      contribute to Al resistance in M. truncatula.

PMID- 18713466
TI  - Targeted disruption of the mouse Csrp2 gene encoding the cysteine- and glycine
      rich LIM domain protein CRP2 result in subtle alteration of cardiac
      ultrastructure.
AB  - BACKGROUND: The cysteine and glycine rich protein 2 (CRP2) encoded by the Csrp2
      gene is a LIM domain protein expressed in the vascular system, particularly in
      smooth muscle cells. It exhibits a bimodal subcellular distribution, accumulating
      at actin-based filaments in the cytosol and in the nucleus. In order to analyze
      the function of CRP2 in vivo, we disrupted the Csrp2 gene in mice and analysed
      the resulting phenotype. RESULTS: A approximately 17.3 kbp fragment of the murine
      Csrp2 gene containing exon 3 through 6 was isolated. Using this construct we
      confirmed the recently determined chromosomal localization (Chromosome 10, best
      fit location between markers D10Mit203 proximal and D10Mit150 central). A gene
      disruption cassette was cloned into exon 4 and a mouse strain lacking functional
      Csrp2 was generated. Mice lacking CRP2 are viable and fertile and have no obvious
      deficits in reproduction and survival. However, detailed histological and
      electron microscopic studies reveal that CRP2-deficient mice have subtle
      alterations in their cardiac ultrastructure. In these mice, the cardiomyocytes
      display a slight increase in their thickness, indicating moderate hypertrophy at
      the cellular level. Although the expression of several intercalated disc
      associated proteins such as beta-catenin, N-RAP and connexin-43 were not affected
      in these mice, the distribution of respective proteins was changed within heart
      tissue. CONCLUSION: We conclude that the lack of CRP2 is associated with
      alterations in cardiomyocyte thickness and hypertrophy.

PMID- 18713467
TI  - A novel survival model of cardioplegic arrest and cardiopulmonary bypass in rats:
      a methodology paper.
AB  - BACKGROUND: Given the growing population of cardiac surgery patients with
      impaired preoperative cardiac function and rapidly expanding surgical techniques,
      continued efforts to improve myocardial protection strategies are warranted.
      Prior research is mostly limited to either large animal models or ex vivo
      preparations. We developed a new in vivo survival model that combines
      administration of antegrade cardioplegia with endoaortic crossclamping during
      cardiopulmonary bypass (CPB) in the rat. METHODS: Sprague-Dawley rats were
      cannulated for CPB (n = 10). With ultrasound guidance, a 3.5 mm balloon
      angioplasty catheter was positioned via the right common carotid artery with its
      tip proximal to the aortic valve. To initiate cardioplegic arrest, the balloon
      was inflated and cardioplegia solution injected. After 30 min of cardioplegic
      arrest, the balloon was deflated, ventilation resumed, and rats were weaned from
      CPB and recovered. To rule out any evidence of cerebral ischemia due to right
      carotid artery ligation, animals were neurologically tested on postoperative day
      14, and their brains histologically assessed. RESULTS: Thirty minutes of
      cardioplegic arrest was successfully established in all animals. Functional
      assessment revealed no neurologic deficits, and histology demonstrated no gross
      neuronal damage. CONCLUSION: This novel small animal CPB model with cardioplegic
      arrest allows for both the study of myocardial ischemia-reperfusion injury as
      well as new cardioprotective strategies. Major advantages of this model include
      its overall feasibility and cost effectiveness. In future experiments long-term
      echocardiographic outcomes as well as enzymatic, genetic, and histologic
      characterization of myocardial injury can be assessed. In the field of myocardial
      protection, rodent models will be an important avenue of research.

PMID- 18713469
TI  - Incidental littoral cell angioma of the spleen.
AB  - BACKGROUND: Littoral cell angioma (LCA) is a recently described primary vascular
      neoplasm of the spleen that may be associated with other malignancies and may
      itself also have malignant potential. CASE PRESENTATION: We present a case of LCA
      that was discovered incidentally in a 52-year-old woman who presented with
      biliary colic at the time of consultation for cholecystectomy. This vascular
      neoplasm was evaluated by ultrasound, CT, MRI, Tc-99m labelled red blood cell
      scintigraphy, and core biopsy. A splenectomy revealed LCA by pathological
      evaluation. Post-operative outcome was favourable with no evidence of
      complication or recurrent disease. Following this case presentation, clinical,
      radiographic, and pathological features of LCA will be reviewed as well as recent
      advances in our understanding of this uncommon splenic lesion. CONCLUSION: LCA is
      a rare, generally benign, primary vascular tumour of the spleen that typically is
      discovered incidentally. Individuals diagnosed with this tumour must be carefully
      evaluated to exclude primary, secondary, and synchronous malignancies.

PMID- 18713468
TI  - Novel insights into the unfolded protein response using Pichia pastoris specific
      DNA microarrays.
AB  - BACKGROUND: DNA Microarrays are regarded as a valuable tool for basic and applied
      research in microbiology. However, for many industrially important microorganisms
      the lack of commercially available microarrays still hampers physiological
      research. Exemplarily, our understanding of protein folding and secretion in the
      yeast Pichia pastoris is presently widely dependent on conclusions drawn from
      analogies to Saccharomyces cerevisiae. To close this gap for a yeast species
      employed for its high capacity to produce heterologous proteins, we developed
      full genome DNA microarrays for P. pastoris and analyzed the unfolded protein
      response (UPR) in this yeast species, as compared to S. cerevisiae. RESULTS: By
      combining the partially annotated gene list of P. pastoris with de novo gene
      finding a list of putative open reading frames was generated for which an
      oligonucleotide probe set was designed using the probe design tool TherMODO (a
      thermodynamic model-based oligoset design optimizer). To evaluate the performance
      of the novel array design, microarrays carrying the oligo set were hybridized
      with samples from treatments with dithiothreitol (DTT) or a strain overexpressing
      the UPR transcription factor HAC1, both compared with a wild type strain in
      normal medium as untreated control. DTT treatment was compared with literature
      data for S. cerevisiae, and revealed similarities, but also important differences
      between the two yeast species. Overexpression of HAC1, the most direct control
      for UPR genes, resulted in significant new understanding of this important
      regulatory pathway in P. pastoris, and generally in yeasts. CONCLUSION: The
      differences observed between P. pastoris and S. cerevisiae underline the
      importance of DNA microarrays for industrial production strains. P. pastoris
      reacts to DTT treatment mainly by the regulation of genes related to chemical
      stimulus, electron transport and respiration, while the overexpression of HAC1
      induced many genes involved in translation, ribosome biogenesis, and organelle
      biosynthesis, indicating that the regulatory events triggered by DTT treatment
      only partially overlap with the reactions to overexpression of HAC1. The high
      reproducibility of the results achieved with two different oligo sets is a good
      indication for their robustness, and underlines the importance of less stringent
      selection of regulated features, in order to avoid a large number of false
      negative results.

PMID- 18713470
TI  - A compartment model of VEGF distribution in blood, healthy and diseased tissues.
AB  - BACKGROUND: Angiogenesis is a process by which new capillaries are formed from
      pre-existing blood vessels in physiological (e.g., exercise, wound healing) or
      pathological (e.g., ischemic limb as in peripheral arterial disease, cancer)
      contexts. This neovascular mechanism is mediated by the vascular endothelial
      growth factor (VEGF) family of cytokines. Although VEGF is often targeted in anti
      angiogenic therapies, there is little knowledge about how its concentration may
      vary between tissues and the vascular system. A compartment model is constructed
      to study the VEGF distribution in the tissue (including matrix-bound, cell
      surface receptor-bound and free VEGF isoforms) and in the blood. We analyze the
      sensitivity of this distribution to the secretion rate, clearance rate and
      vascular permeability of VEGF. RESULTS: We find that, in a physiological context,
      VEGF concentration varies approximately linearly with the VEGF secretion rate.
      VEGF concentration in blood but not in tissue is dependent on the vascular
      permeability of healthy tissue. Model simulations suggest that relative VEGF
      increases are similar in blood and tissue during exercise and return to baseline
      within several hours. In a pathological context (tumor), we find that blood VEGF
      concentration is relatively insensitive to increased vascular permeability in
      tumors, to the secretion rate of VEGF by tumors and to the clearance. However, it
      is sensitive to the vascular permeability in the healthy tissue. Finally, the
      VEGF distribution profile in healthy tissue reveals that about half of the VEGF
      is complexed with the receptor tyrosine kinase VEGFR2 and the co-receptor
      Neuropilin-1. In diseased tissues, this binding can be reduced to 15% while VEGF
      bound to the extracellular matrix and basement membranes increases. CONCLUSION:
      The results are of importance for physiological conditions (e.g., exercise) and
      pathological conditions (e.g., peripheral arterial disease, coronary artery
      disease, cancer). This mathematical model can serve as a tool for understanding
      the VEGF distribution in physiological and pathological contexts as well as a
      foundation to investigate pro- or anti-angiogenic strategies.

PMID- 18713471
TI  - A robust linear regression based algorithm for automated evaluation of peptide
      identifications from shotgun proteomics by use of reversed-phase liquid
      chromatography retention time.
AB  - BACKGROUND: Rejection of false positive peptide matches in database searches of
      shotgun proteomic experimental data is highly desirable. Several methods have
      been developed to use the peptide retention time as to refine and improve peptide
      identifications from database search algorithms. This report describes the
      implementation of an automated approach to reduce false positives and validate
      peptide matches. RESULTS: A robust linear regression based algorithm was
      developed to automate the evaluation of peptide identifications obtained from
      shotgun proteomic experiments. The algorithm scores peptides based on their
      predicted and observed reversed-phase liquid chromatography retention times. The
      robust algorithm does not require internal or external peptide standards to train
      or calibrate the linear regression model used for peptide retention time
      prediction. The algorithm is generic and can be incorporated into any database
      search program to perform automated evaluation of the candidate peptide matches
      based on their retention times. It provides a statistical score for each peptide
      match based on its retention time. CONCLUSION: Analysis of peptide matches where
      the retention time score was included resulted in a significant reduction of
      false positive matches with little effect on the number of true positives.
      Overall higher sensitivities and specificities were achieved for database
      searches carried out with MassMatrix, Mascot and X!Tandem after implementation of
      the retention time based score algorithm.

PMID- 18713472
TI  - A method for genotype validation and primer assessment in heterozygote-deficient
      species, as demonstrated in the prosobranch mollusc Hydrobia ulvae.
AB  - BACKGROUND: In studies where microsatellite markers are employed, it is essential
      that the primers designed will reliably and consistently amplify target loci. In
      populations conforming to Hardy-Weinberg equilibrium (HWE), screening for
      unreliable markers often relies on the identification of heterozygote
      deficiencies and subsequent departures from HWE. However, since many populations
      naturally deviate from HWE, such as many marine invertebrates, it can be
      difficult to distinguish heterozygote deficiencies resulting from unreliable
      markers from natural processes. Thus, studies of populations that are suspected
      to deviate from HWE naturally would benefit from a method to validate genotype
      data-sets and test the reliability of the designed primers. Levels of
      heterozygosity are reported for the prosobranch mollusc Hydrobia ulvae (Pennant)
      together with a method of genotype validation and primer assessment that utilises
      two primer sets for each locus. Microsatellite loci presented are the first
      described for the species Hydrobia ulvae; the five loci presented will be of
      value in further study of populations of H. ulvae. RESULTS: We have developed a
      novel method of testing primer reliability in naturally heterozygote deficient
      populations. After the design of an initial primer set, genotyping in 48 Hydrobia
      ulvae specimens using a single primer set (Primer set_A) revealed heterozygote
      deficiency in six of the seven loci examined. Redesign of six of the primer pairs
      (Primer set_B), re-genotyping of the successful individuals from Primer set_A
      using Primer set_B, and comparison of genotypes between the two primer sets,
      enabled the identification of two loci (Hulv-06 & Hulv-07) that showed a high
      degree of discrepancy between primer sets A and B (0% & only 25% alleles
      matching, respectively), suggesting unreliability in these primers. The
      discrepancies included changes from heterozygotes to homozygotes or vice versa,
      and some individuals who also displayed new alleles of unexpected sizes. Of the
      other four loci examined (Hulv-01, Hulv-03, Hulv-04, & Hulv-05), all showed more
      than 95% agreement between primer sets. Hulv-01, Hulv-03, & Hulv-05 displayed
      similar levels of heterozygosity with both primer sets suggesting that these loci
      are indeed heterozygote deficient, while Hulv-08 showed no deficiency in either
      primer set. CONCLUSION: The simple method described to identify unreliable
      markers will prove a useful technique for many population studies, and also
      emphasises the dangers in using a single primer set and assuming marker
      reliability in populations shown to naturally deviate from HWE.

PMID- 18713474
TI  - Empowerment interventions, knowledge translation and exchange: perspectives of
      home care professionals, clients and caregivers.
AB  - BACKGROUND: Few studies have examined empowerment interventions as they actually
      unfold in home care in the context of chronic health problems. This study aims to
      document the empowerment process as it plays out in interventions with adults
      receiving home care services. METHODS/DESIGN: The qualitative design chosen is a
      fourth generation evaluation combined with case studies. A home care team of a
      health and social services center situated in the Eastern Townships (Quebec,
      Canada) will be involved at every step in the study. A sample will be formed of
      15 health care professionals and 30 of their home care clients and caregiver.
      Semi-structured interviews, observations of home care interventions and socio
      demographic questionnaires will be used to collect the data. Nine instruments
      used by the team in prior studies will be adapted and reviewed. A personal log
      will document the observers' perspectives in order to foster objectivity and the
      focus on the intervention. The in-depth qualitative analysis of the data will
      illustrate profiles of enabling interventions and individual empowerment.
      DISCUSSION: The ongoing process to transform the health care and social services
      network creates a growing need to examine intervention practices of health care
      professionals working with clients receiving home care services. This study will
      provide the opportunity to examine how the intervention process plays out in real
      life situations and how health care professionals, clients and caregivers
      experience it. The intervention process and individual empowerment examined in
      this study will enhance the growing body of knowledge about empowerment.

PMID- 18713473
TI  - General practitioners' views on reattribution for patients with medically
      unexplained symptoms: a questionnaire and qualitative study.
AB  - BACKGROUND: The successful introduction of new methods for managing medically
      unexplained symptoms in primary care is dependent to a large degree on the
      attitudes, experiences and expectations of practitioners. As part of an
      exploratory randomised controlled trial of reattribution training, we sought the
      views of participating practitioners on patients with medically unexplained
      symptoms, and on the value of and barriers to the implementation of reattribution
      in practice. METHODS: A nested attitudinal survey and qualitative study in
      sixteen primary care teams in north-west England. All practitioners participating
      in the trial (n = 74) were invited to complete a structured survey. Semi
      structured interviews were undertaken with a purposive sub-sample of survey
      respondents, using a structured topic guide. Interview transcripts were used to
      identify key issues, concepts and themes, which were grouped to construct a
      conceptual framework: this framework was applied systematically to the data.
      RESULTS: Seventy (95%) of study participants responded to the survey. Survey
      respondents often found it stressful to work with patients with medically
      unexplained symptoms, though those who had received reattribution training were
      more optimistic about their ability to help them. Interview participants trained
      in reattribution (n = 12) reported that reattribution increased their confidence
      to practice in a difficult area, with heightened awareness, altered perceptions
      of these patients, improved opportunities for team-building and transferable
      skills. However general practitioners also reported potential barriers to the
      implementation of reattribution in routine clinical practice, at the level of the
      patient, the doctor, the consultation, diagnosis and the healthcare context.
      CONCLUSION: Reattribution training increases practitioners' sense of competence
      in managing patients with medically unexplained symptoms. However, barriers to
      its implementation are considerable, and frequently lie outside the control of a
      group of practitioners generally sympathetic to patients with medically
      unexplained symptoms and the purpose of reattribution. These findings add further
      to the evidence of the difficulty of implementing reattribution in routine
      general practice.

PMID- 18713475
TI  - Correlation between CD4 counts of HIV patients and enteric protozoan in different
      seasons - an experience of a tertiary care hospital in Varanasi (India).
AB  - BACKGROUND: Protozoan infections are the most serious among all the superimposed
      infections in HIV patients and claim a number of lives every year. The line of
      treatment being different for diverse parasites necessitates a definitive
      diagnosis of the etiological agents to avoid empirical treatment. Thus, the
      present study has been aimed to elucidate the associations between diarrhoea and
      CD4 counts and to study the effect of HAART along with management of diarrhoea in
      HIV positive patients. This study is the first of its kind in this area where an
      attempt was made to correlate seasonal variation and intestinal protozoan
      infestations. METHODS: The study period was from January 2006 to October 2007
      wherein stool samples were collected from 366 HIV positive patients with diarrhea
      attending the ART centre, inpatient department and ICTC of S.S. hospital, I.M.S.,
      B.H.U., Varanasi. Simultaneously, CD4 counts were recorded to assess the status
      of HIV infection vis-a-vis parasitic infection. The identification of pathogens
      was done on the basis of direct microscopy and different staining techniques.
      RESULTS: Of the 366 patients, 112 had acute and 254 had chronic diarrhea. The
      percentages of intestinal protozoa detected were 78.5% in acute and 50.7% in
      chronic cases respectively. Immune restoration was observed in 36.6% patients
      after treatment on the basis of clinical observation and CD4 counts. In 39.8% of
      HIV positive cases Cryptosporidium spp. was detected followed by Microsporidia
      spp. (26.7%). The highest incidence of intestinal infection was in the rainy
      season. However, infection with Cyclospora spp. was at its peak in the summer.
      Patients with chronic diarrhea had lower CD4 cell counts. The maximum parasitic
      isolation was in the patients whose CD4 cell counts were below 200 cells/microl.
      CONCLUSION: There was an inverse relation between the CD4 counts and duration of
      diarrhea. Cryptosporidium spp. was isolated maximum among all the parasites in
      the HIV patients. The highest incidence of infection was seen in the rainy
      season.

PMID- 18713476
TI  - Partial duplication of the PRLR and SPEF2 genes at the late feathering locus in
      chicken.
AB  - BACKGROUND: One of the loci responsible for feather development in chickens is K.
      The K allele is partially dominant to the k+ allele and causes a retard in the
      emergence of flight feathers at hatch. The K locus is sex linked and located on
      the Z chromosome. Therefore, the locus can be utilized to produce phenotypes that
      identify the sexes of chicks at hatch. Previous studies on the organization of
      the K allele concluded the integration of endogenous retrovirus 21 (ev21) into
      one of two large homologous segments located on the Z chromosome of late
      feathering chickens. In this study, a detailed molecular analysis of the K locus
      and a DNA test to distinguish between homozygous and heterozygous late feathering
      males are presented. RESULTS: The K locus was investigated with quantitative PCR
      by examining copy number variations in a total of fourteen markers surrounding
      the ev21 integration site. The results showed a duplication at the K allele and
      sequence analysis of the breakpoint junction indicated a tandem duplication of
      176,324 basepairs. The tandem duplication of this region results in the partial
      duplication of two genes; the prolactin receptor and the gene encoding sperm
      flagellar protein 2. Sequence analysis revealed that the duplication is similar
      in Broiler and White Leghorn. In addition, twelve late feathering animals,
      including Broiler, White Leghorn, and Brown Layer lines, contained a 78 bp
      breakpoint junction fragment, indicating that the duplication is similar in all
      breeds. The breakpoint junction was used to develop a TaqMan-based quantitative
      PCR test to allow distinction between homozygous and heterozygous late feathering
      males. In total, 85.3% of the animals tested were correctly assigned, 14.7% were
      unassigned and no animals were incorrectly assigned. CONCLUSION: The detailed
      molecular analysis presented in this study revealed the presence of a tandem
      duplication in the K allele. The duplication resulted in the partial duplication
      of two genes; the prolactin receptor and the gene encoding sperm flagellar
      protein 2. Furthermore, a DNA test was developed to distinguish between
      homozygous and heterozygous late feathering males.

PMID- 18713477
TI  - Photographic measurement of upper-body sitting posture of high school students: a
      reliability and validity study.
AB  - BACKGROUND: All the reported measures of sitting posture, as well as photographs,
      have one flaw, as these measures are external to the body. These measures use
      calculations from external bony landmarks to estimate spinal posture, on the
      understanding that what is being measured externally reflects the shape, health
      and performance of structures of the underlying spine. Without a comparative
      measure of the relative position of the structures of the spine, the validity of
      any external spinal posture measure cannot be established. This paper reports on
      a study which tests the validity of photographs to measure adolescent sitting
      posture. METHODS: The study was conducted in a laboratory at the Department of
      Human Biology, University of Cape Town. A random sample of 40 adolescents were
      recruited from the Cape metropolitan schools, to detect differences of three
      degrees or more between the repeated measures of upright, normal or slouched
      posture (photographs) and between the posture photographs and LODOX measures.
      Eligible participants were healthy male and female subjects aged 15 or 16 years
      old, in Grade 10, and who were undertaking Computer or Computype studies at their
      schools. Two posture measurement tools were used in the study, namely:
      Photographs were taken using the Photographic Posture Analysis Method (PPAM) and
      Radiographs were taken using the LODOX (LODOX (Pty) Ltd) system. Subjects'
      posture was assessed in simulated computer workstations. The following angles
      were measured: the sagittal head angle, cervical angle, protraction/retraction
      angle, arm angle and the thoracic angle. RESULTS: Data from 39 subjects (19
      males, 20 females) was used for analysis (17 15-year-olds (7 boys and 10 girls),
      22 16-year-olds (12 boys and 10 girls)). All but one photographic angle showed
      moderate to good correlation with the LODOX angles (Pearson r values 0.67-0.95)
      with the exception being the shoulder protraction/retraction angle Pearson r
      values. Bland Altman limits of agreement illustrated a slight bias for all
      angles. The reliability study findings from repeated photographs demonstrated
      moderate to good correlation of all angles (ICC values 0.78-0.99). CONCLUSION:
      The findings of this study suggest that photographs provide valid and reliable
      indicators of the position of the underlying spine in sitting. Clinically it is
      important to know whether a patient is showing true progression in relation to a
      postural intervention. Based on the results of this study, the PPAM can be used
      in practice as a valid measure of sitting posture.

PMID- 18713478
TI  - Pharmaceutical industry marketing: understanding its impact on women's health.
AB  - The delivery of modern health care entails significant involvement from the
      pharmaceutical industry, including developing and manufacturing drugs. However,
      the industry also has tremendous influence on the practice of medicine through
      its considerable marketing efforts, both to patients through direct to consumer
      advertising, and to physicians through detailing, providing samples, continuing
      medical education, and other efforts. This article will review the role that
      pharmaceutical marketing plays in health care, and the substantial evidence
      surrounding its influence on patient and physician behaviors, with additional
      discussion of the medical device industry, all with particular attention to
      women's health. Understanding the effects of pharmaceutical marketing on women's
      health, through discussion of relevant examples-including oral contraceptive
      pills, drugs for premenstrual dysphoric disorder, Pap smear cytology techniques,
      and neonatal herpes prophylaxis-will help ensure that women receive unbiased,
      evidenced-based care. We will conclude with a discussion of guidelines that have
      been proposed by professional organizations, policy makers, and universities, to
      assist physicians in managing exposure to pharmaceutical marketing.

PMID- 18713479
TI  - Dysmenorrhea: contemporary perspectives.
AB  - Dysmenorrhea affects up to 80% of reproductive age women, in many cases causing
      sufficient pain to dramatically affect social and occupational roles. The
      prevalence varies across ethnic groups, which in part may reflect varying
      cultural attitudes toward women and menstruation. Key identified risk factors for
      dysmenorrhea include age of menarche, body mass, dietary habits, associated
      uterine bleeding disorders, comorbid pelvic pathology, and psychosocial problems.
      While much of the focus on the pathogenesis of dysmenorrhea has focused on
      aberrant inflammatory mediators in the uterine environment, recent studies using
      experimental quantitative sensory testing suggest central processing of pain is
      enhanced in many of these women as well, similar to both irritable bowel syndrome
      and painful bladder syndrome, which are closely related visceral pain disorders.
      The mainstays of treatment include nonsteroidal antiinflammatories and combined
      oral contraceptives; although only the former has extensive level I evidence to
      support its efficacy. Surgical treatments (presacral neurectomy or uterosacral
      nerve ablation) appear to be beneficial in a subset of women, but are associated
      with small, but serious, risks of visceral or vascular injury. Complementary and
      alternative treatments such as vitamin B1 and magnesium supplementation have not
      been studied as extensively but show some promise as well. In particular,
      treatments targeting central aberrations in pain processing, as used in chronic
      pain management, may prove beneficial as a more multidimensional approach to this
      common malady is accepted in our field.

PMID- 18713480
TI  - A comparison of patient perceptions and physician practice patterns related to
      HIV testing.
AB  - In the past 25 years, human immunodeficiency virus (HIV) and acquired
      immunodeficiency syndrome (AIDS) have become leading causes of illness and death
      in the United States. Over 1 million people are living with HIV/AIDS in this
      country, yet there continue to be many individuals who are unaware of their HIV
      status. Efforts have been made by the Centers for Disease Control and Prevention
      to increase awareness by recommending universal testing in healthcare setting for
      all individuals ages 13-64, for both public health and personal health reasons.
      As women are one of the fastest-growing segments of the population with new HIV
      diagnoses, obstetrician-gynecologists are in a unique position to address this
      issue by recommending HIV testing to both pregnant and nonpregnant women. In this
      article, we compare the results of two recent studies conducted by the American
      College of Obstetricians and Gynecologists-one which examined obstetrician
      gynecologists' practice patterns related to HIV testing and recommendations and
      the other which assessed patients' perceptions of HIV testing and recommendations
      by their obstetrician-gynecologists. The results of this comparison raise
      intriguing questions about the similarities and differences between what
      obstetrician-gynecologists report doing and what their patients perceive them
      doing as it relates to HIV testing recommendations.

PMID- 18713481
TI  - Nutritional intervention in patients with periodontal disease: clinical,
      immunological and microbiological variables during 12 months.
AB  - The role of nutrition in onset, progression and treatment of periodontitis has
      not been thoroughly evaluated. In the present prospective clinical study, we
      investigated the influence of a nutritional intervention on changes in clinical,
      microbiological and immunological periodontal variables during a period of 12
      months in patients with the metabolic syndrome and chronic periodontitis. Twenty
      female subjects with the metabolic syndrome and mild to moderate chronic
      periodontitis participated in a guided nutritional intervention programme.
      Examinations were assessed before, and at 2 weeks, 3, 6 and 12 months after
      intervention. Clinical measurements included probing depth, Loe and Silness
      gingival index and Quigley-Hein plaque index. In gingival crevicular fluid,
      periodontopathogens, levels of IL-1beta and IL-6 as well as the activity of
      granulocyte elastase were determined. In stimulated saliva, antioxidative and
      oxidative variables were measured. After 12 months the following significant
      changes could be observed: reduction of clinical probing depth (2.40 v. 2.20 mm;
      P < 0.001), reduction of gingival inflammation (gingival index 1.13 v. 0.9; P <
      0.001), reduced concentrations of IL-1beta (4.63 v. 1.10 pg/ml per site; P <
      0.001) as well as IL-6 (1.85 v. 0.34 pg/ml per site; P = 0.022) in gingival
      crevicular fluid. Bacterial counts in gingival crevicular fluid as well as
      oxidative and antioxidative variables in saliva showed no significant changes.
      Only salivary catalase showed a tendency to lower values. These findings indicate
      that in patients with the metabolic syndrome wholesome nutrition might reduce
      inflammatory variables of periodontal disease and promote periodontal health.

PMID- 18713482
TI  - Ganglioside composition of differentiated Caco-2 cells resembles human colostrum
      and neonatal rat intestine.
AB  - Gangliosides are glycosphingolipids found in cell membranes and human milk with
      important roles in cell proliferation, differentiation, growth, adhesion,
      migration, signalling and apoptosis. Similar changes in ganglioside composition
      occur during embryonic development, lactation and cancer cell differentiation. It
      is not known, however, whether ganglioside compositional changes that occur in
      differentiating colon cancer cells reflect changes that occur during intestinal
      development. The Caco-2 cell line is commonly used to study physiological and
      pathophysiological processes in the small intestine and colon. Therefore, to
      examine this question, undifferentiated and differentiated Caco-2 cells were
      grown and total lipid was extracted from cell supernatant fractions using the
      Folch method. The upper aqueous phase containing gangliosides was collected and
      purified. Total gangliosides were measured as ganglioside-bound N-acetyl
      neuraminic acid, while individual ganglioside content was quantified via a
      colorimetric assay for sialic acid and scanning densitometry. The total
      ganglioside content of differentiated Caco-2 cells was 2.5 times higher compared
      with undifferentiated cells. Differentiated Caco-2 cells had significantly more
      (N-acetylneuraminyl) 2-galactosylglucosyl ceramide (GD3) and polar gangliosides,
      and a lower N-acetylneuraminylgalactosylglucosylceramide (GM3):GD3 ratio than
      undifferentiated cells. The present study demonstrates that the total ganglioside
      content and individual ganglioside composition of differentiated Caco-2 cells are
      similar to those of human colostrum and neonatal rat intestine. Differentiated
      Caco-2 cells may therefore be an alternative model for studying physiological and
      pathological processes in the small intestine and colon, and may help to
      elucidate possible functions for specific gangliosides in development and
      differentiation. Further research using more sensitive techniques of ganglioside
      analysis is needed to confirm these findings.

PMID- 18713483
TI  - Effects of food energy on cognitive performance: no support from event-related
      potentials (yet?).
AB  - Several reviews of behavioural studies have concluded that some foods may have
      beneficial effects on cognitive performance. The present review summarises
      findings from studies using event-related potentials to investigate the food
      effects on brain activity underlying cognition. Despite initial positive
      indications from observational studies, subsequent studies with a within-subject
      design have not consistently confirmed these effects. This could be due to
      several factors, e.g. the use of attention tests (in contrast to memory tests
      employed in behavioural studies) and the lack of a control condition in some
      instances. Future studies could benefit from measuring cognitive performance with
      more difficult tests that tap into cognitive domains other than attention, using
      an appropriately controlled cross-over design, and a more systematic variation
      and complete description and characterisation of the food intervention.

PMID- 18713484
TI  - The epidemiology of depression in metropolitan China.
AB  - BACKGROUND: Previous surveys on depression in China focused on prevalence
      estimates without providing a detailed epidemiological profile. METHOD: Face-to
      face household interviews were conducted with a multi-stage household probability
      sample of 2633 adults (age > or = 18 years) in Beijing and 2568 in Shanghai
      between November 2001 and February 2002. The World Health Organization Composite
      International Diagnostic Interview (CIDI) was used to assess major depressive
      episode (MDE) according to Diagnostic and Statistical Manual of Mental Disorders
      (DSM)-IV criteria. RESULTS: The lifetime prevalence and 1-year prevalence
      estimates of DSM-IV/CIDI MDE were 3.6% [95% confidence interval (CI) 2.8-4.4%]
      and 1.8% (95% CI 1.2-2.4%) respectively. No significant gender difference was
      found in these estimates. Respondents born in 1967 or later were at elevated
      lifetime risk compared with respondents born in earlier cohorts. The mean age of
      onset was 30.3 years. Among those reporting 1-year MDE, 15.7, 51.8, 25.3 and 6.4%
      reported mild, moderate, severe and very severe symptoms respectively; 4.8, 2.6
      and 3.2% reported suicidal ideation, plans, and recent attempts in the same year
      respectively. Respondents with 1-year MDE reported a mean of 27.5 days out of
      role owing to their depression in the year before interview. Significant co
      morbidity was found between MDE and other mental disorders [odds ratio (OR) 22.0]
      and chronic physical disorders (OR 3.2). Only 22.7% of respondents with 1-year
      MDE sought treatment. CONCLUSIONS: The low prevalence and insignificant gender
      difference, but not patterns of onset, course, co-morbidity, and impairment,
      distinguish the epidemiological profile of MDE in metropolitan China from those
      in other countries.

PMID- 18713485
TI  - Cognitive memory control in borderline personality disorder patients.
AB  - BACKGROUND: It has been demonstrated that the mechanism of cognitive memory
      control in humans is sustained by the hippocampus and prefrontal cortices, which
      have been found to be structurally and functionally abnormal in borderline
      personality disorder (BPD). We investigated whether the memory control mechanism
      is affected in BPD. METHOD: Nineteen Diagnostic and Statistical Manual of Mental
      Disorders (DSM)-IV BPD patients and 19 matched healthy controls (HC) performed a
      specific think/no-think paradigm exploring the capacity of remembering and
      suppressing pair of words previously learned. After the think-no think phase, the
      second member of each word pair has to be remembered either when subjects are
      presented with the cue word showed at the beginning of the test (Same Probe Test;
      SPT) or when they are presented with an extra-list categorical word (Independent
      Probe Test; IPT). We evaluated the effect of suppression and of retrieval
      activity on later retention of words. RESULTS: Both on the SPT and on the IPT, HC
      showed the expected improvement of memory retrieval on to-be-remembered words,
      unlike BPD patients. On the SPT, HC, but not BPD patients, correctly recalled
      significantly more words among remembered words (RW) than among suppressed words
      (SW). Similarly to HC, subjects with BPD without a history of childhood abuse
      showed a significantly higher percentage of correctly recalled words among RW
      than among SW. CONCLUSIONS: The mechanism of active retrieval of memories and of
      improvement through repetition is impaired in BPD, particularly in those who
      experienced traumatic experiences. This impairment might play an important role,
      possibly resulting in the emergence of unwanted memories and dissociative
      symptoms.

PMID- 18713486
TI  - The effect of positive mood induction on emotional processing in euthymic
      individuals with bipolar disorder and controls.
AB  - BACKGROUND: Many studies have used negative mood induction techniques to
      investigate the effect of emotional state on cognitive performance but positive
      mood induction paradigms have been used less frequently. The objective of this
      study was to investigate the effect of positive mood induction on emotional
      processing in euthymic individuals with bipolar disorder (BD) and controls.
      METHOD: Previously, we reported that positive mood induction using a novel
      technique based on feedback produced a longer-lasting effect in euthymic
      individuals with BD than controls (Farmer et al. 2006). Here we report the effect
      of mood induction on two tests of emotional processing, the Affective Go/No-go
      test (AGNG) and the Cambridge Gamble task (CGT), on which BD patients in the
      manic phase differ in their performance from controls. RESULTS: Following
      positive mood induction, bipolar cases exhibited a positive emotional bias on the
      AGNG and performed more slowly than controls on the CGT, particularly when making
      more difficult decisions. CONCLUSIONS: These data confirm that positive mood
      induction is more effective in individuals with BD than controls. They also
      suggest that alterations in decision making and attentional biases occur even
      with transient and subtle changes in mood in bipolar disorder.

PMID- 18713487
TI  - Early striatal hypertrophy in first-episode psychosis within 3 weeks of
      initiating antipsychotic drug treatment.
AB  - BACKGROUND: We and others have reported that patients experiencing their first
      episode of psychosis already have significant structural brain abnormalities.
      Antipsychotics seem to reverse subcortical volume deficits after months of
      treatment. However, the early impact of medication on brain morphology is not
      known. METHOD: Forty-eight individuals in their first episode of psychosis
      underwent magnetic resonance imaging (MRI) brain scanning. Twenty-six were
      antipsychotic naive and 22 were newly treated with antipsychotic medication for a
      median period of 3 weeks. In each group, 80% of subjects received a diagnosis of
      schizophrenia. The two groups were balanced for age, sex, handedness, ethnicity,
      height, years of education, paternal socio-economic status (SES) and Positive and
      Negative Syndrome Scale (PANSS) score. Group differences in whole-brain grey
      matter were compared voxel by voxel, using Brain Activation and Morphological
      Mapping (BAMM) software. We also conducted testing of group differences with
      region-of-interest (ROI) measurements of the caudate nucleus. RESULTS: Relative
      to the untreated group, those receiving antipsychotic medication for 3-4 weeks
      had significantly greater grey-matter volumes in the bilateral caudate and
      cingulate gyri, extending to the left medial frontal gyrus. ROI analysis
      confirmed that, in treated patients, the right and left caudate nuclei were
      significantly larger by 10% (p<0.039, two-tailed) and 9% (p<0.048, two-tailed)
      respectively. CONCLUSIONS: Early striatal grey-matter enlargement may occur
      within the first 3-4 weeks of antipsychotic treatment. Possible reasons for
      putative striatal hypertrophy and its implications are discussed.

PMID- 18713488
TI  - Body composition in psychotic disorders: a general population survey.
AB  - BACKGROUND: The literature suggests an association between obesity and
      schizophrenia but fat mass and fat-free mass, which have been shown to be more
      predictive of all-cause mortality than only waist circumference and obesity [body
      mass index (BMI) 30 kg/m2], have not been reported in psychotic disorders. We
      examined the detailed body composition of people with different psychotic
      disorders in a large population-based sample. METHOD: We used a nationally
      representative sample of 8082 adult Finns aged 30 years with measured
      anthropometrics (height, weight, waist circumference, fat percentage, fat-free
      mass and segmental muscle mass). Psychiatric diagnoses were based on a consensus
      procedure utilizing the Structured Clinical Interview for DSM-IV (SCID)
      interview, case-notes and comprehensive register data. RESULTS: Schizophrenia
      (including schizo-affective disorder) was associated with obesity [odds ratio
      (OR) 2.3, 95% confidence interval (CI) 1.5-3.6], abdominal obesity (waist
      circumference 88 cm for women, 102 cm for men) (OR 2.2, 95% CI 1.3-3.6) and with
      higher fat percentage (mean difference 3.8%, 95% CI 2.0-5.7%), adjusted for age
      and gender, than in the remaining sample. The associations between schizophrenia
      and low fat-free mass and decreased muscle mass on trunk and upper limbs became
      statistically significant after adjusting for BMI. After further adjusting for
      current antipsychotic medication, education, diet and smoking, schizophrenia
      remained associated with obesity (OR 1.9, 95% CI 1.1-3.6) and abdominal obesity
      (OR 3.8, 95% CI 1.5-9.4). Participants with affective psychoses did not differ
      from the general population. CONCLUSIONS: Individuals with schizophrenia have
      metabolically unfavorable body composition, comprising abdominal obesity, high
      fat percentage and low muscle mass. This leads to increased risk of metabolic and
      cardiovascular diseases.

PMID- 18713489
TI  - Attention deficit hyperactivity disorder (ADHD): gender- and age-related
      differences in neurocognition.
AB  - BACKGROUND: Despite the growing recognition that the clinical symptom
      characteristics associated with attention deficit hyperactivity disorder (ADHD)
      persist into adulthood in a high proportion of subjects, little is known about
      the persistence of neurocognitive deficits in ADHD. The objective was twofold:
      (1) to conduct a meta-analysis of neuropsychological studies to characterize
      attentional performance in subjects with adult ADHD by examining differences in
      ADHD versus normal control subjects; and (2) to investigate whether these
      differences vary as a function of age and gender. METHOD: Twenty-five
      neuropsychological studies comparing subjects with adult ADHD and healthy
      controls were evaluated. Statistical effect size was determined to characterize
      the difference between ADHD and control subjects. Meta-regression analysis was
      applied to investigate whether the difference between ADHD and control subjects
      varied as a function of age and gender across studies. RESULTS: Tests measuring
      focused and sustained attention yielded an effect size with medium to large
      magnitude whereas tests of simple attention resulted in a small to medium effect
      size in terms of poorer attention functioning of ADHD subjects versus controls.
      On some of the measures (e.g. Stroop interference), a lower level of attention
      functioning in the ADHD group versus the controls was associated with male
      gender. CONCLUSIONS: Adult ADHD subjects display significantly poorer functioning
      versus healthy controls on complex but not on simple tasks of attention, and the
      degree of impairment varies with gender, with males displaying a higher level of
      impairment.

PMID- 18713490
TI  - Efficacy and tolerance of a hydrocolloid dressing containing hyaluronic acid for
      the treatment of leg ulcers of venous or mixed origin.
AB  - OBJECTIVE: This study was aimed at comparing efficacy and tolerance of a new
      hydrocolloid dressing containing hyaluronic acid (HC + HA) to a reference
      hydrocolloid not containing hyaluronic acid (HC) in the treatment of leg ulcers
      of venous or mixed origin. RESEARCH DESIGN AND METHODS: This was an open,
      prospective study, randomized in parallel groups, in which 125 patients were
      enrolled and treated for up to 42 days. The primary efficacy criterion was the
      reduction of the wound area; other efficacy criteria were the condition of the
      wound bed, and of the surrounding skin, and presence and severity of symptoms
      such as pain and itching. RESULTS: After 42 days of treatment the median
      reduction of ulcer area was -42.6% (95% confidence interval [CI]: -66.6; -5.7)
      and -31.0% (95% CI: -51.6; -8.8) in the HC + HA group and in the reference HC
      group, respectively. The difference between treatments was not statistically
      significant. A reduction > or = 90% of the initial ulcer area was seen in 15
      patients in the HC + HA dressing group and in only seven patients in the HC
      dressing group. Changes in wound bed condition in the two groups were not
      significantly different, except for a more marked reduction of fibrinous tissue
      in the HC + HA dressing group (p = 0.04), at Day 28. Both treatments were well
      tolerated. CONCLUSIONS: The HC + HA dressing was equally well tolerated and with
      a trend to be more effective than the reference HC dressing in the treatment of
      leg ulcers of venous or mixed origin. Further research is needed to confirm these
      findings.

PMID- 18713492
TI  - Tuberculosis prevalence surveys: an educational series.

PMID- 18713491
TI  - Changes in intraocular pressure following a switch from latanoprost monotherapy
      to latanoprost/timolol fixed combination therapy in patients with primary open
      angle glaucoma or ocular hypertension: results from a clinical practice database.
AB  - AIMS: To assess the incremental change in intraocular pressure (IOP) levels in
      patients with primary open-angle glaucoma or ocular hypertension, insufficiently
      treated with topical ocular hypotensive monotherapy or combination therapy and
      changed to the latanoprost/timolol fixed-combination therapy (LTFC). METHODS: The
      glaucoma database of the Glasgow Royal Infirmary was reviewed retrospectively to
      identify patients > or = 18 years of age with primary open-angle glaucoma or
      ocular hypertension in at least one eye who had been switched to LTFC from a
      previous monotherapy or combination therapy. Ninety patients were identified, and
      59 (66%) had changed to LTFC from latanoprost monotherapy (LM). The analysis
      focused on this subgroup because few patients were changed from any other single
      therapy. At least one documented patient visit following the change to LTFC was
      required. The within-subject difference in IOP levels (IOP on LM-IOP on LTFC) was
      calculated for each case, and the statistical significance of the mean change in
      IOP was analysed using a 2-sided Student's paired t-test with a 0.05 alpha level.
      RESULTS: The mean decrease in IOP after changing to LTFC from LM was 2.6 mmHg
      (95% confidence interval = 1.6, 3.6), from 21.4 (SD = 3.5) mmHg to 18.8 (SD =
      4.2) mmHg (p = 0.002). CONCLUSIONS: LTFC provides significant incremental IOP
      reduction in patients with primary open-angle glaucoma or ocular hypertension who
      require additional IOP reduction following treatment with LM.

PMID- 18713493
TI  - Stopping tuberculosis: time to turn urgent attention to hospitals.

PMID- 18713494
TI  - The rising incidence and clinical relevance of Mycobacterium malmoense: a review
      of the literature.
AB  - The incidence of Mycobacterium malmoense infections compared to other non
      tuberculous mycobacteria (NTM) has increased since 1980, especially in northern
      Europe. Based on various epidemiological and clinical reports outside northern
      Europe, there is a wide distribution of these infections. Infections with M.
      malmoense cause pulmonary disease comparable with tuberculosis (TB). The main
      extra-pulmonary disease type is paediatric cervical lymphadenitis. M. malmoense
      isolates are clinically significant in about 70-80% of patients. Like other NTM
      infections, M. malmoense is often found in patients with chronic obstructive
      pulmonary disease (COPD) and may cause serious morbidity and mortality when
      inadequately treated. The best treatment consists of a 2-year regimen with
      rifampicin and ethambutol. The literature on infections with M. malmoense is
      reviewed with respect to epidemiology, clinical presentation, treatment and
      outcome.

PMID- 18713495
TI  - Drug-metabolising enzyme polymorphisms and predisposition to anti-tuberculosis
      drug-induced liver injury: a meta-analysis.
AB  - BACKGROUND: Although some case-control studies have investigated the association
      between drug-metabolising enzyme (DME) gene polymorphisms and susceptibility to
      anti-tuberculosis drug-induced liver injury (ATLI), their results are
      conflicting, mainly due to limited power. OBJECTIVE: To review the literature
      systematically, by means of a meta-analytical review, to evaluate the putative
      association and provide a quantitative summary estimate on the association with
      ATLI. DESIGN: We searched the databases of MEDLINE, PubMed, EMBASE and CBMdisc
      from 1966 to May 2007 using 'DME', 'hepatotoxicity', 'genetic polymorphism',
      'genetic susceptibility' in combination with 'antitubercular agents', performed a
      manual search of citations from relevant original studies and review articles,
      and corresponded with authors. RESULTS: Nine eligible articles were included in
      this meta-analysis, including five on N-acetyltransferase 2 (NAT2), four on
      cytochrome P450 2E1 (CYP2E1) and two on glutathione S-transferase (GST) studies,
      separately. The overall ORs of ATLI risk associated with NAT2 homozygous variant
      genotype (mt/mt), CYP2E1 homozygous wild genotype (*1A/*1A), GSTM1 homozygous
      null genotype (null/null) and GSTT1 homozygous null genotype (null/null) were
      respectively 1.93 (95%CI 0.81-4.62), 2.22 (95%CI 1.06-4.66), 2.62 (95%CI 1.45
      4.75) and 1.18 (95%CI 0.61-2.29). In addition, the OR for Asian ATLI associated
      with the NAT2 homozygous variant (mt/mt) and the combined genotype (w/w + w/mt)
      was 2.52 (95%CI 1.49-4.26). CONCLUSIONS: NAT2 mt/mt, CYP2E1*1A/*1A and GSTM1
      null/null were observed to increase the risk of ATLI in tuberculosis patients.
      Our results support the hypothesis that NAT2 mt, CYP2E1*1A and GSTM1 null have a
      modest effect on genetic susceptibility to ATLI, but no significant evidence for
      GSTT1 null/null.

PMID- 18713496
TI  - Tuberculosis prevalence surveys: rationale and cost.
AB  - This article is the first of the educational series 'Assessing tuberculosis (TB)
      prevalence through population-based surveys'. The series will give overall
      guidance in conducting cross-sectional surveys of pulmonary TB (PTB) disease. TB
      prevalence surveys are most valuable in areas where notification data obtained
      through routine surveillance are of unproven accuracy or incomplete, and in areas
      with an estimated prevalence of bacteriologically confirmed TB of more than 100
      per 100,000 population. To embark on a TB prevalence survey requires commitment
      from the national TB programme, compliance in the study population, plus
      availability of trained staff and financial resources. The primary objective of
      TB prevalence surveys is to determine the prevalence of PTB in the general
      population aged >or=15 years. Limitations of TB prevalence surveys are their
      inability to assess regional or geographic differences in prevalence of TB,
      estimate the burden of childhood TB or estimate the prevalence of extra-pulmonary
      TB. The cost of a prevalence survey is typically US$ 4-15 per person surveyed,
      and up to US$ 25 per person with radiographic screening. A survey of 50,000
      people, of limited precision, would typically cost US$ 200,000-1,250,000.

PMID- 18713497
TI  - Performance and acceptability of the FluoLED Easy module for tuberculosis
      fluorescence microscopy.
AB  - SETTING: Tuberculosis (TB) reference laboratory in Bangkok, Thailand, and two
      health centres in Dar es Salaam, Tanzania. OBJECTIVES: To assess the performance
      and user-friendliness of a light-emitting diode (LED) module (FluoLED Easy) for
      TB fluorescence microscopy (FM). DESIGN: Equivalence study vs. conventional FM in
      Bangkok using blinded re-reading; routine detection in the health centres in Dar
      es Salaam compared to Ziehl-Neelsen (ZN) over 2 years, with rechecking of FM
      smears. RESULTS: For 461 smears re-read, 99.1% concordance with conventional FM
      was obtained. FluoLED introduction caused a lasting increase in detection in the
      routine of each of the health centres by on average 20%. Blinded rechecking
      failed due to unreliable registration. Onsite rechecking of a convenience sample
      showed absence of false-positive results in one centre and confusion with
      artefacts that could have been avoided by more training in the other. LED FM was
      highly appreciated, with both laboratories refusing to revert to ZN as originally
      intended. CONCLUSIONS: A simple microscope with a FluoLED module can yield
      results equivalent to those of conventional FM. Low cost, technical
      appropriateness and excellent acceptance justify its use in low-income settings,
      contrary to classical systems. LED FM can lead to increased sensitivity, but for
      optimal yield good training and quality assurance remain essential requirements.

PMID- 18713498
TI  - Monitoring the performance of mycobacteriology laboratories: a proposal for
      standardized indicators.
AB  - SETTING: Thailand Tuberculosis (TB) Active Surveillance Network: Bangkok, Chiang
      Rai, Phuket, Tak and Ubon-Ratchathani, Thailand. BACKGROUND: Mycobacteriology
      laboratories in resource-limited, high TB burden settings are expanding to
      perform conventional solid media culture and broth-based mycobacteriology
      culture. Indicators that measure how well a laboratory performs sputum microscopy
      have been developed and broadly implemented. Routine monitoring of sputum culture
      performance, however, is not as common. DESIGN: We implemented indicators for
      monitoring the quality of laboratory services in five province-level
      mycobacteriology culture facilities in Thailand. These indicators were derived
      from literature review, consultation with subject matter experts and our program
      experience. CONCLUSIONS: We believe that an international consensus document
      providing monitoring guidelines for mycobacteriology laboratories is urgently
      needed.

PMID- 18713499
TI  - Cost-effectiveness of novel diagnostic tools for the diagnosis of tuberculosis.
AB  - SETTING: The potential cost-effectiveness of improved diagnostic tests for
      tuberculosis (TB) in resource-limited settings is unknown. OBJECTIVE: To estimate
      the incremental cost-effectiveness of a hypothetical new point-of-care TB
      diagnostic test in South Africa, Brazil and Kenya. DESIGN: Decision-analysis
      model, adding four diagnostic interventions (sputum smear microscopy, new test,
      smear plus new test and smear plus TB culture) to a baseline of existing
      infrastructure without smear. RESULTS: Adding sputum smear was estimated to be
      more cost-effective (incremental cost per disability-adjusted life year [DALY] of
      $86 [South Africa], $131 [Brazil], $38 (Kenya]) than a new TB diagnostic with 70%
      sensitivity, 95% specificity and price of $20 per test ($198 [South Africa], $275
      [Brazil], $84 [Kenya]). However, compared to sputum smear, smear plus new test
      averted 46-49% more DALYs per 1000 TB suspects (321 vs. 215 [South Africa], 243
      vs. 166 [Brazil], 790 vs. 531 [Kenya]), at an incremental cost of $170 (Kenya) to
      $625 (Brazil) per DALY averted. Cost-effectiveness was most sensitive to the
      specificity and price of the new test, the baseline TB case detection rate and
      the discount rate. CONCLUSION: Novel diagnostic tests for TB are potentially
      highly cost-effective. Cost-effectiveness is maximized by high-specificity, low
      cost tests deployed to regions with poor infrastructure.

PMID- 18713500
TI  - Diagnosis of tuberculous lymphadenitis in Ethiopia: correlation with culture,
      histology and HIV status.
AB  - SETTING: Butajira, Southern Ethiopia. OBJECTIVE: To compare the diagnostic
      capacity of the clinical criteria for tuberculous lymphadenitis (TBLN) with
      histological and/or culture results and to assess the association of human
      immunodeficiency virus (HIV) with tuberculosis (TB) lymphadenitis. DESIGN:
      Patients (n=171) were included in the study from October 2005 until July 2006 at
      Butajira Hospital. Laboratory tests were performed to confirm TBLN. HIV status
      was identified in TBLN patients and retrospectively in 1608 healthy individuals.
      RESULT: A total of 136/161 (84.5%) patients were diagnosed with TBLN by
      histology. TBLN was culture-confirmed in 107/156 (68.6%) patients. The
      sensitivity, specificity, positive and negative predictive values of histology
      were respectively 92.5%, 49%, 79.8% and 75% when compared to culture as gold
      standard. Patients positive for TBLN by cytology and Ziehl-Neelsen (ZN) were also
      positive by histology and culture. Among the 143 confirmed TBLN patients, nine
      (6.3%) were HIV-positive. Of the 1608 healthy individuals, 77 (4.8%) were HIV
      positive. Younger age (P=0.0001), female sex (P=0.016), not being married
      (P=0.0001) and illiteracy (P=0.016) showed a strong association with HIV in
      healthy individuals. CONCLUSION: Clinical criteria alone over-diagnosed TBLN by
      15.4% compared to histological and/or bacteriological results. The HIV prevalence
      in TBLN patients and healthy individuals was the same.

PMID- 18713501
TI  - Completion of isoniazid preventive therapy among HIV-infected patients in
      Tanzania.
AB  - SETTING: Isoniazid preventive therapy (IPT) has not been widely implemented due
      to questions about acceptance, adherence and side effects. OBJECTIVE: To examine
      factors related to completion of IPT among human immunodeficiency virus (HIV)
      infected subjects in Tanzania. DESIGN: HIV-infected subjects in the DarDar TB
      vaccine trial with CD4 cell counts >or=200 cells/mm(3) and a positive tuberculin
      skin test (TST) were counseled, offered IPT for 6 months and seen monthly.
      RESULTS: Among 1932 subjects, TST results were positive in 631 (33%): 568 (90%)
      were offered IPT, 565 (99%) accepted and three (<1%) refused. Of the 565 subjects
      who accepted IPT, 493 (87%) completed treatment and 72 (13%) did not. Non
      completion was physician-initiated in 24 (33%, due to active TB or side effects),
      patient-initiated in 42 (58%, due to self-cessation or loss to follow-up) and due
      to death in 6 (8%, unrelated to IPT). Interviews were conducted among 109
      completers and 20 non-completers (12 physician- and 8 patient-initiated).
      Completers were motivated by fear of TB (44%), understanding the importance of
      IPT (32%) and counseling (22%). Patient-initiated non-completers were dissuaded
      by stigma (58%), side effects (14%) and travel distance (1%). CONCLUSIONS: HIV
      infected subjects provided with counseling, monthly follow-up and travel
      reimbursement have high rates of IPT completion with minimal side effects.

PMID- 18713502
TI  - A health systems assessment of the KwaZulu-Natal tuberculosis programme in the
      context of increasing drug resistance.
AB  - SETTING: High mortality and high transmission rates of extensively drug-resistant
      tuberculosis (XDR-TB) in KwaZulu-Natal Province of South Africa have highlighted
      the role of hospitals in the spread of TB and drug-resistant TB. OBJECTIVES: To
      determine the operational effectiveness of the National TB Programme (NTP) at a
      regional/district hospital and its referral clinics. DESIGN: In this multi
      faceted retrospective case study, a framework was developed to evaluate the
      different components of the TB services, their performance in relation to each
      other and the system as a whole. Different methods used included structured and
      semi-structured interviews, retrospective medical record reviews and
      retrospective register reviews. RESULTS: Only 18% of those diagnosed with smear
      positive pulmonary TB (PTB) in the hospital laboratory completed their treatment
      and 11% were cured. Clinicians did not adhere to the diagnostic guidelines of the
      NTP. In the TB register, 85% of PTB cases were diagnosed in the absence of sputum
      microscopy. Chest X-rays alone were used to diagnose PTB in 45% of the records
      reviewed. In addition, clinicians failed to document a clinical history
      suggestive of TB. Only 66 (29%) of the hospital's 225 smear-positive PTB patients
      reached the clinics for completion of their treatment. CONCLUSION: System
      failures, together with inadequate knowledge and understanding of clinicians,
      undermined the effectiveness of the NTP. A reduction in TB and drug-resistant
      forms of TB is dependent on effective diagnosis, treatment and improved
      communication systems between the hospital, laboratory and its down-referral
      clinics.

PMID- 18713503
TI  - An exploration of the causes of tuberculosis stigma in an urban district in
      Ghana.
AB  - SETTING: Shama Ahanta East Metropolitan District, Ghana. OBJECTIVES: To explore
      tuberculosis (TB) stigma and to elucidate how it operates in community settings
      and within the health care system to affect case finding and treatment adherence.
      DESIGN: Individual interviews and focus groups with TB patients, health care
      workers and community members. RESULT: Ten causes of TB stigma emerged from the
      data: fear of infection, physical frailty, association with human
      immunodeficiency virus/acquired immune-deficiency syndrome, perceived causes and
      spread of TB, outdated societal beliefs and practices about TB, public health
      practice and discourse, health staff's own fear of TB, self-stigmatisation by TB
      patients, judgement, blaming and shaming TB patients, and past experiences with
      TB. Fear of infection was identified as the main cause of TB stigma, with an
      element of fear recognised in all the other nine causes, named the 'moderating
      elements'. The moderating elements enhance the fear of infection, and fear of
      infection enhances the moderating elements. CONCLUSION: The fear attached to TB
      underlies the beliefs, attitudes, actions and behaviours of the whole community
      when interacting with patients. These findings will be used to advocate for
      complete integration of TB services into the general health care system and
      involvement of community members in TB services in the district.

PMID- 18713504
TI  - Initial default among diagnosed sputum smear-positive pulmonary tuberculosis
      patients in Andhra Pradesh, India.
AB  - BACKGROUND: Under the Indian Revised National TB Control Programme (RNTCP), smear
      positive pulmonary tuberculosis (PTB) patients not confirmed as starting
      treatment are reported as 'initial defaulters'. SETTING: Twenty districts of
      Andhra Pradesh State, India. OBJECTIVE: To evaluate reasons for treatment non
      initiation in smear-positive PTB patients diagnosed and reported as initial
      defaulters by the NTP. DESIGN: A cross-sectional survey conducted of all reported
      initial defaulters during the period July-September 2006. RESULTS: Of 1304
      reported initial defaulters, 619 (47.5%) had been placed on treatment, having
      been incorrectly reported due to poor documentation of patients referred for
      treatment in the same district or whose treatment initiation was delayed until
      the subsequent quarter. Of the 685 (4.5% of the total diagnosed) who were
      confirmed initial defaulters, 350 (51%) were untraceable, 152 (22%) had died
      before treatment initiation, 38 (5.5%) were treated privately, 93 (13.5%) had
      other reasons (e.g., refusal of treatment, chronic case, etc.) and no data were
      available for 52 (8%). CONCLUSIONS: Nearly 5% of smear-positive PTB patients
      diagnosed in the study period were confirmed as not having initiated treatment
      under the RNCTP. Improvements in address recording may assist efforts to retrieve
      these patients for treatment. Additional evaluations are needed of improved
      counselling of TB suspects to prevent initial default, and of reasons for death
      before treatment initiation.

PMID- 18713505
TI  - The value of end-of-treatment chest radiograph in predicting pulmonary
      tuberculosis relapse.
AB  - SETTING: Patients with cavitary pulmonary tuberculosis (TB) on baseline chest
      radiograph (CXR) who remain culture-positive after 8 weeks of treatment are at
      high risk of relapse. The role of end-of-treatment (EOT) CXR in predicting
      relapse is unclear. OBJECTIVE: To determine whether EOT CXR independently
      predicts TB relapse. DESIGN: We conducted a secondary analysis of a randomized
      trial of intermittent treatment using rifapentine in the continuation phase of TB
      treatment among 1004 human immunodeficiency virus seronegative adults with
      culture-proven pulmonary TB. RESULTS: Relapse occurred in 17.3% of subjects with
      persistent cavity on EOT CXR, in 7.6% of subjects with a cavity that resolved by
      EOT, and 2.5% (P=0.002 for trend) of subjects who never had a cavity. In
      multivariable analysis, patients with persistent cavity on EOT CXR were
      significantly more likely to relapse than patients with no cavity on baseline or
      2-month CXR (hazard ratio [HR] 4.22, 95%CI 2.00-8.91), and were more likely to
      relapse than subjects whose early cavity had resolved by EOT CXR (HR 1.92, 95%CI
      1.09-3.39). CONCLUSION: A persistent cavity after 6 months of TB treatment was
      independently associated with disease relapse after controlling for other
      variables. EOT CXR may help predict those likely to relapse.

PMID- 18713506
TI  - Risk factors for multidrug-resistant tuberculosis in Hong Kong.
AB  - SETTING: Previous anti-tuberculosis treatment is a widely reported risk factor
      for multidrug-resistant tuberculosis (MDR-TB), whereas other risk factors are
      less well described. In Hong Kong, the clinical characteristics of MDR-TB have
      not been systematically evaluated. OBJECTIVE: To explore the risk factors for MDR
      TB in Hong Kong. DESIGN: MDR-TB patients treated between 1999 and 2003 were
      compared with non-MDR-TB patients by stratification of previous anti-tuberculosis
      treatment. RESULTS: One hundred and fifty-six MDR-TB patients, including 93 with
      and 63 without a previous history of anti-tuberculosis treatment, were
      identified. Among the 322 non-MDR-TB controls, respectively 192 and 130 patients
      did and did not have a previous history of anti-tuberculosis treatment. Using
      logistic regression analysis, non-permanent residents (OR 6.85, 95%CI 1.38
      34.09), frequent travel (OR 2.48, 95%CI 1.07-5.74) and younger age were found to
      be independent predictors of MDR-TB in previously treated patients, whereas
      living on financial assistance just failed to reach statistical significance (OR
      2.75, 95%CI 0.98-7.68, P=0.05). In the treatment-naive group, despite significant
      differences in baseline characteristics among MDR-TB and non-MDR-TB patients, no
      independent predictor variables could be identified. CONCLUSION: In Hong Kong,
      non-permanent residents, frequent travel and young age were independent
      predictors of MDR-TB among previously treated patients.

PMID- 18713507
TI  - Decreased phosphorylation of STAT-1, STAT-4 and cytokine release in MDR-TB
      patients with primary resistance.
AB  - SETTING: We recently showed that treatment failure rate was higher among
      multidrug-resistant tuberculosis (MDR-TB) patients without a previous history of
      tuberculosis (TB) treatment, or so-called 'primary resistance'. OBJECTIVE: To
      investigate the phosphorylation levels of signal transducers and activators of
      transcription-1 (STAT-1) and STAT-4 and the subsequent cytokine release as a
      possible cause of a poor prognosis in MDR-TB patients with primary resistance.
      DESIGN: Ten patients with successfully treated pulmonary TB without resistance,
      12 MDR-TB patients with acquired resistance and 10 MDR-TB patients with primary
      resistance were enrolled. After 24 h stimulation of peripheral blood mononuclear
      cells (PBMC) with interferon-gamma (IFN-gamma), interleukin-12 (IL-12), purified
      protein derivative (PPD), or lysate of Mycobacterium tuberculosis, flow
      cytometric analysis of intracellular pSTAT-1 and pSTAT-4 were performed and
      secretion of IFN-gamma, IL-12p40 and tumour necrosis factor-alpha (TNF-alpha) was
      measured in culture supernatant. RESULTS: The mean fluorescent intensities of
      pSTAT-1 and pSTAT-4 in PBMC of MDR-TB patients with primary resistance decreased
      on stimulation of IFN-gamma, PPD or lysate of M. tuberculosis when compared with
      patients with acquired resistance. In addition, secretion of IFN-gamma, IL-12p40
      and TNF-alpha in these patients decreased on various stimuli. CONCLUSION:
      Decreased phosphorylation of STAT-1, STAT-4, and of subsequent cytokine release,
      might be associated with a poor prognosis in MDR-TB patients with primary
      resistance.

PMID- 18713508
TI  - Knowledge, attitudes and practice of university students regarding waterpipe
      smoking in Pakistan.
AB  - OBJECTIVES: To study the awareness, perceptions and practice of university
      students in Karachi, Pakistan, with regard to shisha (waterpipe) smoking. DESIGN:
      Cross-sectional survey conducted among students at four different universities of
      Karachi, selected through random cluster sampling. RESULTS: A total of 450
      participants, 59.6% males (n=268) and 40.4% females (n=182), were included in the
      study. About half of the participants reported having ever smoked shisha (n=241,
      53.6%). On examining factors associated with starting shisha smoking, curiosity
      was found to be the most common reason (n=148, 61.4%), followed by pleasure
      seeking (n=113, 46.9%), peer pressure (n=55, 22.8%), boredom (n=43, 17.8%) and
      stress (n=26, 10.8%). Of 241 participants who had ever smoked waterpipes, the
      majority (n=149, 61.8%) were current smokers. A vast majority of participants
      (n=269, 60%) considered waterpipe smoking to be less unhealthy than cigarette
      smoking. Boredom in youth, use of waterpipe in leisure activities and peer
      pressure were identified as the most common reasons for the escalating popularity
      of waterpipe smoking in Pakistan. CONCLUSIONS: Waterpipe smoking is very popular
      among Pakistani university students, and knowledge among university students
      about the dangers of waterpipe smoking is alarmingly low.

PMID- 18713509
TI  - Cigarettes and waterpipe smoking among medical students in Syria: a cross
      sectional study.
AB  - OBJECTIVES: To investigate tobacco use, beliefs and attitudes among medical
      students in Syria. METHODS: A cross-sectional study of a random sample of 570
      medical students (first and fifth year) registered at the Damascus University
      Faculty of Medicine in 2006-2007. We used a self-administered questionnaire for
      demo-graphic information, smoking behaviour (cigarette, waterpipe), family and
      peer smoking, attitudes and beliefs about smoking and future role in advising
      patients to quit smoking. RESULTS: The overall prevalence of tobacco use was
      10.9% for cigarettes (15.8% men, 3.3% women), 23.5% for waterpipe (30.3% men,
      13.4% women) and 7.3% for both (10.1% men, 3.1% women). Both smoking methods were
      more popular among the fifth year students (15.4% and 27%) compared to their
      younger counterparts (6.6% and 19.7%). Regular smoking patterns predominated for
      cigarettes (62%), while occasional use patterns predominated for waterpipes
      (83%). More than two thirds of students (69%) thought they might not address or
      would have difficulty addressing smoking in their future patients. CONCLUSION:
      The level of tobacco use among Syrian medical students is alarming and highlights
      the rapidly changing patterns of waterpipe use, especially among female students.
      Medical schools should work harder to tackle this phenomenon and address it more
      efficiently in their curricula.

PMID- 18713510
TI  - Wood smoke-associated lung disease: a clinical, functional, radiological and
      pathological description.
AB  - BACKGROUND: Approximately half of the world's population, and up to 90% of
      households in rural areas of developing countries, depend on biomass for cooking
      and heating. SETTING: The National Institute of Respiratory Diseases, Mexico
      City. OBJECTIVE: To describe wood smoke-associated lung disease (WSLD). DESIGN:
      Description of the clinical, functional and radiological manifestations of
      patients with WSLD, and a comparison of pathological findings of patients who
      died of WSLD and smokers who died of chronic bronchitis. RESULTS: All patients
      with WSLD were non-smoking women with chronic bronchitis, in whom asthma,
      bronchiectasis, tuberculosis, congestive heart failure, extreme obesity and alfa
      1 antitrypsin deficiency had been excluded. All patients used wood for cooking
      and had been exposed to wood smoke for a median of 45 years. Dyspnoea, airway
      obstruction, air trapping, increased airway resistance, pathological evidence of
      anthracosis, chronic bronchitis, centrilobular emphysema and pulmonary
      hypertension were present in most patients with WSLD. Bronchial squamous
      metaplasia was a common finding. There were no significant differences in the
      histopathological findings between patients with WSLD and smokers. Diffuse
      interstitial fibrosis was absent in all patients. CONCLUSIONS: Patients with WSLD
      have obstructive lung disease, chronic bronchitis, emphysema and pulmonary
      hypertension comparable to smokers.

PMID- 18713511
TI  - Pyrazinamide serum levels in childhood tuberculosis.
AB  - Pyrazinamide (PZA) is one of the first-line drugs in anti-tuberculosis treatment.
      In the present study, PZA serum levels in 34 children aged 1 to 14 years were
      measured either after oral application of PZA alone or after combination therapy
      with isoniazid and rifampicin. Serum levels did not differ statistically with
      age, in PZA monotherapy or in combination therapy. With a dosage of 30 mg/kg PZA,
      efficient serum levels were reached. Because PZA is distributed uniformly in the
      body, serum levels are related to body weight, and a dose of 30 mg/kg bodyweight
      is appropriate in children.

PMID- 18713512
TI  - A randomised controlled trial of high-dose isoniazid adjuvant therapy for
      multidrug-resistant tuberculosis.

PMID- 18713513
TI  - Simultaneous detection and quantification of amphetamines, diazepam and its
      metabolites, cocaine and its metabolites, and opiates in hair by LC-ESI-MS-MS
      using a single extraction method.
AB  - A liquid chromatography-tandem mass spectrometry method was developed and
      validated for the simultaneous identification and quantification of amphetamines,
      diazepam and its metabolites, cocaine and its metabolites, and opiates from hair
      using a single extraction method. As part of the method development, Gemini C18,
      Synergi Hydro RP, and Zorbax Stablebond-Phenyl LC columns were tested with three
      different mobile phases. Analyte recovery and limit of detection were evaluated
      for two different solid-phase extraction methods that used Bond Elut Certify and
      Clean Screen cartridges. Phosphate buffer (pH 5.0) was chosen as the optimum hair
      incubation medium because of the high stability of cocaine and 6
      monoacetylmorphine using this method and faster sample preparation. The optimized
      method was fully validated. Linearity was established over the concentration
      range 0.2-10 ng/mg hair, and the correlation coefficients were all greater than
      0.99. Total extraction recoveries were greater than 76%, detection limits were
      between 0.02 and 0.09 ng/mg, and the intra- and interday imprecisions were
      generally less than 20% in spiked hair. The intra- and interbatch imprecision of
      the method for a pooled authentic hair sample ranged from 1.4 to 23.4% relative
      standard deviation (RSD) and 8.3 to 25.4% RSD, respectively, for representative
      analytes from the different drug groups. The percent matrix effect ranged from
      63.5 to 135.6%, with most analytes demonstrating ion suppression. Sixteen
      postmortem samples collected from suspected drug-related deaths were analyzed for
      the 17 drugs of abuse and metabolites included in the method. The method was
      sufficiently sensitive and specific for the analysis of drugs and metabolites in
      postmortem hair samples. There is scope for the inclusion of other target drugs
      and metabolites in the method.

PMID- 18713514
TI  - Comparison of cannabinoid pharmacokinetic properties in occasional and heavy
      users smoking a marijuana or placebo joint.
AB  - Cannabinoid pharmacokinetics in occasional users is well studied, but the
      interpretation of data from heavy users is difficult. In the present study, blood
      pharmacokinetic properties were investigated in occasional and heavy users in
      cannabis and placebo conditions. The results obtained with occasional users were
      in contrast to those of the heavy users who admitted cannabis use on 4-25
      occasions during the previous week. Of the 12 heavy users, 10 exhibited up to
      12.3 microg/L Delta(9)-tetrahydrocannabinol (THC) prior to smoking. During the 8
      h after smoking, the distribution and elimination patterns were comparable to
      those of the occasional users and the concentrations returned to 68-196% (median
      110%) of the initial values. However, the maximal concentration and the areas
      under the curves were significantly higher with marked interindividual variation.
      In contrast to the cannabis conditions, the THC concentrations in the placebo
      phase decreased more slowly (elimination half-life 17.5-43.5 h vs. 1.0-5.9 h) in
      accordance with a late elimination phase. The elimination half-lives of 11
      hydroxy-THC and 11-nor-9-carboxy-THC in th cannabis conditions (medians 3.1 h and
      6.2 h, respectively) were longer than those of THC, which was different in the
      placebo phase (medians 7.2 h and 13.0 h, respectively). From the results, it must
      be cautioned that cannabinoid blood concentrations from heavy users in a late
      elimination phase may be difficult to distinguish from concentrations measured in
      occasional users after acute cannabis use.

PMID- 18713515
TI  - Development and validation of an EI-GC-MS method for the determination of
      methadone and its major metabolites (EDDP and EMDP) in human breast milk.
AB  - Methadone is used extensively for the maintenance of opioid-addicted pregnant
      women. Because methadone and the two major metabolites, 2-ethylidene-1,5-dimethyl
      3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP),
      are excreted into breast milk, a sensitive and specific gas chromatographic-mass
      spectrometric method has been developed, optimized, and validated for their
      quantitative determination in human breast milk. The procedure combined protein
      precipitation with acetonitrile and solid-phase extraction, using Isolute Confirm
      HCX mixed-mode SPE columns, with minimal matrix effect. The optimum extraction
      conditions for all three analytes were evaluated using spiked human breast milk,
      and the recovery exceeded 93.0%. This assay uses methadone-d(9) as internal
      standard for the determination of methadone and EMDP, and EDDP-d(3) for the
      determination of EDDP. Calibration curves were linear within the range of 2.00
      1000 microg/L for methadone (R(2) > 0.995) and 1.00-500 microg/L for EDDP (R(2)
      >0.997) and EMDP (R(2) > 0.991). Intra- and interday accuracy and precision were
      within the range of 0.8-5.7% and 1.3-5.2%, respectively, for all analytes. The
      stability study was assessed by fortifying human breast milk with methadone and
      its metabolites at two different concentrations and keeping the samples at
      different temperature conditions. The analytes were found to be stable in breast
      milk at room temperature for at least 4 h and at -20 degrees C for at least one
      month. The method was used for the determination of methadone and its major
      metabolites in human breast milk samples obtained from women in the postpartum
      period participating in a methadone maintenance program.

PMID- 18713516
TI  - Simultaneous quantification of amphetamine and methamphetamine in meconium using
      ISOLUTE HM-N-supported liquid extraction columns and GC-MS.
AB  - A procedure is described for the rapid extraction and quantification of
      amphetamine and methamphetamine from meconium using ISOLUTE HM-N-supported liquid
      extraction columns and gas chromatography-mass spectrometry (GC-MS). Because of
      the matrix complexity of meconium samples, extraction and sample preparation
      prior to instrumental analysis can prove difficult and time-consuming. The
      present study introduces a novel sample preparation technique for the
      simultaneous quantification of amphetamine and methamphetamine in meconium using
      GC-MS. Extraction of both analytes was achieved using ISOLUTE HM-N-supported
      liquid extraction columns containing a modified form of diatomaceous earth.
      Limits of detection for both analytes were 30 ng/g and the lower limit of
      quantitation was 75 ng/g. Linearity was achieved over the range 75-3000 ng/g. The
      methodology showed excellent intrarun precision with %CV values ranging from 2 to
      8% for both analytes. Interrun precision experiments produced %CV values between
      7 and 10% for both analytes. The reported methodology proved suitable for the
      accurate quantification of amphetamine and methamphetamine in meconium samples
      and greatly reduced the sample preparation time normally required for traditional
      solid-phase extraction. The development and validation of such analytical
      methodologies will prove beneficial for the identification of prenatal substance
      abuse, which is an ongoing concern across socioeconomic lines.

PMID- 18713517
TI  - Quantitation of benzodiazepines in urine, serum, plasma, and meconium by LC-MS
      MS.
AB  - A single method for confirmation and quantitation of a panel of commonly
      prescribed benzodiazepines and metabolites, alpha-hydroxyalprazolam, alpha
      hydroxyethylflurazepam, alpha-hydroxytriazolam, alprazolam, desalkylflurazepam,
      diazepam, lorazepam, midazolam, nordiazepam, oxazepam, temazepam, clonazepam, and
      7-aminoclonazepam, was developed for three specimen types, urine, serum/plasma,
      and meconium. Quantitation was by liquid chromatography tandem-mass spectrometry
      (LC-MS-MS) using a Waters Alliance-Quattro Micro system. The instrument was
      operated in multiple reaction monitoring mode with an electrospray ionization
      source in positive ionization mode. The method was evaluated for recovery,
      imprecision, linearity, analytical measurement range, specificity, and carryover.
      Average recovery and imprecision (within-run, between-run, and total % CV) were
      within +/- 15% of the target concentrations for urine (10 to 5000 ng/mL) and
      serum/plasma (10 to 2500 ng/mL) and within +/- 20% for meconium (10 to 5000
      ng/g). In all, 205 patient specimens were analyzed, and the results compared to a
      previous in-house gas chromatography-MS method or LC-MS-MS results from an
      outside laboratory. Oxazepam glucuronide was evaluated as a hydrolysis control
      for the urine and meconium specimens.

PMID- 18713518
TI  - Chiral analysis of methadone and its main metabolite EDDP in postmortem blood by
      liquid chromatography-mass spectrometry.
AB  - A chiral liquid chromatography-tandem mass spectrometry method was developed for
      the measurement of methadone and 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium
      (EDDP) enantiomers in postmortem blood. Blood (0.100 g) was mixed with water and
      aqueous methadone-d(3) and EDDP-d(3) solutions. After addition of NaOH,
      extraction was carried out with butyl acetate. Chromatographic separation was
      performed on a chiral-AGP analytical column (100 mm x 4.0-mm i.d., 5 microm) with
      a mobile phase of acetonitrile/ammonium acetate buffer (10 mM, pH 7.0, 22:78,
      v/v). A Quattro micro mass spectrometer was operated in the positive ion mode
      with an electrospray source. Multiple reaction monitoring was used with two
      transitions for each compound. The calibration curves were linear over the range
      from 0.001 to 2.5 mg/kg blood per enantiomer, and the limit of detection was
      0.001 mg/kg, and the limit of quantitation was 0.003 mg/kg for all compounds. The
      precision (coefficient of variation%) was below 6.3%, and the trueness was 88
      104% for all compounds. R- and S-methadone were measured in femoral blood from 10
      postmortem cases. The R-methadone concentrations extended from 0.006 to 1.235
      mg/kg with a median of 0.41 mg/kg, and the S-methadone concentrations ranged from
      0 to 0.794 mg/kg (median 0.33 mg/kg). The median R/S-ratio was 1.46 (total range
      from 1.00 to 2.62), which tends to be higher than that reported in plasma of
      living subjects.

PMID- 18713519
TI  - Comparison among plasma, serum, and whole blood ethanol concentrations: impact of
      storage conditions and collection tubes.
AB  - How blood samples are processed and stored before being analyzed for alcohol
      levels is of concern in the forensic and toxicological fields, and is important
      in the standardization of research methods. This experiment explored for
      systematic differences in ethanol levels among several methods of processing and
      storing blood samples. Five adults consumed a standard alcoholic drink (0.7 g/kg)
      over a 15-min period, and blood samples were taken 5 times during a 3-h period
      following drinking onset. Samples for plasma and whole blood were drawn into
      Vacutainers containing either an anticoagulant or an anticoagulant plus
      preservative. Samples for serum were drawn into Vacutainers containing no
      additives or a preservative only. Separate sets of samples were analyzed on the
      day of the study, after storage at room temperature (25 degrees C) for 24 h,
      after storage at room temperature for 10 days, or after 10 days of refrigerated
      storage. Neither processing condition (i.e., type of additive) nor storage
      condition significantly affected ethanol levels. Consistent with the literature,
      plasma and serum samples had significantly higher concentrations of ethanol than
      whole blood. This study shows that blood samples containing ethanol at levels
      ranging from 60 to 90 mg/dL (0.06 to 0.09 mg%) are not significantly altered by
      the type of collection tube used or storage condition during a 10-day period.

PMID- 18713520
TI  - Stability of benzodiazepines and cocaine in blood spots stored on filter paper.
AB  - Previous studies have shown that drug concentrations in blood can change during
      storage, especially at room temperature, but even labile drugs such as cocaine
      may be stable in dried blood spots (DBS). A new method has been developed for the
      analysis of hydrolytically labile drugs in blood spots on filter paper in order
      to assess their degradation during a storage period of one month. The drugs
      selected included flunitrazepam, temazepam, oxazepam, lorazepam, nitrazepam,
      diazepam, and cocaine. A Guthrie card 903 was spotted with 100 microL of blood
      containing the drugs at concentrations of 1000 ng/mL and left overnight to dry at
      room temperature. The filter paper was suspended in extraction buffer for 1 h
      with ultrasonication. Drugs were then extracted from the buffer by solid-phase
      extraction using Clean Screen((R)) columns and analyzed by liquid chromatography
      tandem mass spectrometry. Method validation showed that all calibration curves
      were linear over the concentration range 5-200 ng/spot with correlation
      coefficients of 0.994-0.999. Interday and intraday precisions at three
      concentrations (10, 50, and 100 ng/spot) were 1.6-18.3% and 2.8-14.7%,
      respectively. Limits of detection were 0.29-0.74 ng/spot, and lower limits of
      quantitation were 0.99-2.46 ng/spot. Recoveries of all analytes were in the range
      81-106%. DBS were stored in duplicate at room temperature, 4 degrees C, and -20
      degrees C for up to one month. Degradation of the drugs in DBS at all storage
      conditions was less than for the corresponding liquid blood samples stored under
      similar conditions and more than 80% of each analyte could be recovered from the
      samples.

PMID- 18713521
TI  - Urinary buprenorphine concentrations in patients treated with suboxone as
      determined by liquid chromatography-mass spectrometry and CEDIA immunoassay.
AB  - We report on the utility of urine total buprenorphine, total norbuprenorphine,
      and creatinine concentrations in patients treated with Suboxone (a formulation
      containing buprenorphine and naloxone), used increasingly for the maintenance or
      detoxification of patients dependent on opiates such as heroin or oxycodone.
      Patients received 8-24 mg/day buprenorphine. Two-hundred sixteen urine samples
      from 70 patients were analyzed for both total buprenorphine and total
      norbuprenorphine by liquid chromatography-mass spectrometry (LC-MS-MS).
      Buprenorphine concentrations in all 176 samples judged to be unadulterated
      averaged 164 ng/mL, with a standard deviation (SD) of 198 ng/mL. Nine samples
      (4.2%) had metabolite-parent drug ratios < 0.02, and 33 (15.3%) had no detectable
      buprenorphine. The metabolite/parent drug ratio in 166 samples had a range of
      0.07-23.0 (mean = 4.52; SD = 3.97). Fifteen of 96 available urine samples (16.7%)
      had creatinine less than 20 mg/dL. We also found sample adulteration in 7 (7.3%)
      available samples. Using a 5 ng/mL urine buprenorphine cutoff, the sensitivity
      and specificity of the Microgenics homogeneous enzyme immunoassay versus LC-MS-MS
      were 100% and 87.5%, respectively. The 5 ng/mL cutoff Microgenics CEDIA
      buprenorphine assay results agreed analytically with LC-MS-MS in 97.9% of
      samples.

PMID- 18713522
TI  - Detection of clenbuterol in heroin users in twelve postmortem cases at the
      Philadelphia medical examiner's office.
AB  - The presence of clenbuterol, a beta2-adrenergic agonist banned for human use in
      the United States because of its serious side effects, is reported in a series of
      12 postmortem cases in which the cause of death was attributed to illicit drug
      use. During the first three months of 2007, postmortem specimens from cases
      previously screening positive for opiates or fentanyl were screened specifically
      for clenbuterol using enzyme-linked immunosorbent assay. Confirmation of
      clenbuterol was performed using solid-phase extraction, derivatization with
      trimethylboroxine, and analysis utilizing a gas chromatograph-mass spectrometer
      (GC-MS) operated in the full-scan mode. The limits of detection and quantitation
      in blood were 2.5 and 5 ng/mL, respectively. Linearity was from 5 to 100 ng/mL.
      Clenbuterol was positive in 12/106 (11%) drug-related cases and in 12/575 (2.1%)
      of the total cases tested. In each of the 12 cases positive for clenbuterol,
      heroin use was either confirmed by the presence of 6-acetylmorphine or strongly
      suspected by the presence of morphine with a history of heroin abuse. Because the
      use of clenbuterol in the United States is restricted to veterinary medicine, its
      detection is an unexpected finding. Its presence in these cases serves as a
      caution to emergency room physicians and toxicologists to consider and test for
      clenbuterol when treating a suspected heroin user who presents atypically. This
      is the first known series of clenbuterol-positive cases of illicit drug users to
      be reported from a medical examiner's toxicology laboratory.

PMID- 18713523
TI  - UK's National Programme for IT welcomes recommendation for a more sociotechnical
      approach to evaluation: a commentary on the Greenhalgh evaluation of the summary
      care record.

PMID- 18713524
TI  - The use and effectiveness of electronic clinical decision support tools in the
      ambulatory/primary care setting: a systematic review of the literature.
AB  - BACKGROUND: The 1999 Institute of Medicine (IOM) report To Err is Human alerted
      the healthcare industry and the public to the lack of consistency in the delivery
      of quality care to the US population. Clinical decision support systems (CDSS)
      have become a leading response to this report, and to the growing demand for the
      promotion of standards-based care delivery. The objective of this paper is to
      evaluate the recent literature for both the types and effectiveness of electronic
      CDSS in the primary care setting. METHODS: An electronic search of the literature
      was conducted utilising MEDLINE (1996-2006), CINAHL (1982-2006) and all EBM
      Reviews--Cochrane DSR, ACP Journal Club, DARE and CCTR. The search included
      various combinations of the MeSH search terms 'clinical decision support
      systems', 'primary health care', 'ambulatory care' and 'practice guidelines' and
      was limited to articles published from 2000 to 2006. Studies were selected for
      review if they involved either non-randomised observational or randomised
      controlled trials (RCTs) utilising CDSS as a single intervention, were performed
      in an ambulatory primary care setting and included quantifiable outcome measures.
      RESULTS: Seventeen studies were included in the review, including five non
      randomised observational studies and 12 RCTs. Thirteen studies (76%) found either
      positive or variable outcomes related to CDSS intervention with four studies
      (24%) showing no significant effect. CONCLUSION: Although there is validation
      that CDSS has the potential to produce statistically significant improvement in
      outcomes, there is much variability among the types and methods of CDSS
      implementation and resulting effectiveness. As CDSS will likely continue to be at
      the forefront of the march toward effective standards-based care, more work needs
      to be done to determine effective implementation strategies for the use of CDSS
      across multiple settings and patient populations.

PMID- 18713525
TI  - The patient's perspective of computerised records: a questionnaire survey in
      primary care.
AB  - BACKGROUND: The general practice consultation today has become a three-way
      process where patient, doctor and computer interact. Some studies have shown that
      the introduction of the computer has caused concern to some patients, possibly
      affecting their behaviour. If patients are less frank about their problems in a
      computer-mediated consultation this may cause concerns among doctors and become a
      barrier to computer use. OBJECTIVES: A questionnaire was developed to test the
      prevalence of worries among patients about confidentiality breaches of computer
      records and to identify whether those worries translated into a reduction in
      patients' frankness. RESULTS: The study had a 62% response rate. Almost 48% of
      responders had experienced confidentiality worries during past consultations. All
      responders denied withholding any relevant information from their general
      practitioner (GP) as a result of confidentiality worries. Gender, computer
      literacy, knowledge of computer uses in consultation and patients' perceptions of
      computer record safety were selected covariates in the multivariate logistic
      regression model explaining patients' worry. Thirty-three percent of patients
      stated they always understand what their GP is doing at the computer during
      consultation, 9.7% stated they did not ever know; though 64% judged it important
      to know what their GPs were doing. CONCLUSIONS: Patients worry about the
      confidentiality of their computer record and it seems that those less familiar
      with computers, females and those less aware of their GP's actions at the
      computer worry more. Patients' understanding of their GPs' actions at the
      computer during consultation is far from complete and they seem to place great
      importance on this. Those patients who place greatest importance on needing an
      understanding of their GP's actions are those most likely to worry about
      confidentiality.

PMID- 18713526
TI  - Developing a decision support system for tobacco use counselling using primary
      care physicians.
AB  - BACKGROUND: Clinical decision support systems (CDSS) have the potential to
      improve adherence to guidelines, but only if they are designed to work in the
      complex environment of ambulatory clinics as otherwise physicians may not use
      them. OBJECTIVE: To gain input from primary care physicians in designing a CDSS
      for smoking cessation to ensure that the design is appropriate to a clinical
      environment before attempts to test this CDSS in a clinical trial. This approach
      is of general interest to those designing similar systems. Design and approach:
      We employed an iterative ethnographic process that used multiple evaluation
      methods to understand physician preferences and workflow integration. Using
      results from our prior survey of physicians and clinic managers, we developed a
      prototype CDSS, validated content and design with an expert panel, and then
      subjected it to usability testing by physicians, followed by iterative design
      changes based on their feedback. We then performed clinical testing with
      individual patients, and conducted field tests of the CDSS in two primary care
      clinics during which four physicians used it for routine patient visits. RESULTS:
      The CDSS prototype was substantially modified through these cycles of usability
      and clinical testing, including removing a potentially fatal design flaw. During
      field tests in primary care clinics, physicians incorporated the final CDSS
      prototype into their workflow, and used it to assist in smoking cessation
      interventions up to eight times daily. CONCLUSIONS: A multi-method evaluation
      process utilising primary care physicians proved useful for developing a CDSS
      that was acceptable to physicians and patients, and feasible to use in their
      clinical environment.

PMID- 18713527
TI  - A visual study of computers on doctors' desks.
AB  - BACKGROUND: General practice has rapidly computerised over the past ten years,
      thereby changing the nature of general practice rooms. Most general practice
      consulting rooms were designed and created in an era without computer hardware,
      establishing a pattern of work around maximising the doctor-patient relationship.
      General practitioners (GPs) and patients have had to integrate the computer into
      this environment. METHODS: Twenty GPs allowed access to their rooms and
      consultations as part of a larger study. The results are based on an analysis of
      still shots of the consulting rooms. Analysis used dramaturgical methodology;
      thus the room is described as though it is the setting for a play. RESULTS:
      First, several desk areas were identified: a shared or patient area, a working
      area, a clinical area and an administrative area. Then, within that framework, we
      were able to identify two broad categories of setting, one inclusive of the
      patient and one exclusive. CONCLUSION: With the increasing significance of the
      computer in the three-way doctor-patient-computer relationship, an understanding
      of the social milieu in which the three players in the consultation interact (the
      staging) will inform further analysis of the interaction, and allow a framework
      for assessing the effects of different computer placements.

PMID- 18713528
TI  - Measuring the impact of different brands of computer systems on the clinical
      consultation: a pilot study.
AB  - BACKGROUND: UK general practitioners largely conduct computer-mediated
      consultations. Although historically there were many small general practice (GP)
      computer suppliers there are now around five widely used electronic patient
      record (EPR) systems. A new method has been developed for assessing the impact of
      the computer on doctor-patient interaction through detailed observation of the
      consultation and computer use. OBJECTIVE: To pilot the latest version of a method
      to measure the difference in coding and prescribing times on two different brands
      of general practice EPR system. METHOD: We compared two GP EPR systems by
      observing use in real life consultations. Three video cameras recorded the
      consultation and screen capture software recorded computer activity. We piloted
      semi-automated user action recording (UAR) software to record mouse and keyboard
      use, to overcome limitations in manual measurement. Six trained raters analysed
      the videos using data capture software to measure the doctor-patient-computer
      interactions; we used interclass correlation coefficients (ICC) to measure
      reliability. RESULTS: Raters demonstrated high inter-rater reliability for verbal
      interactions and prescribing (ICC 0.74 to 0.99), but for measures of computer use
      they were not reliable. We used UAR to capture computer use and found it more
      reliable. Coded data entry time varied between the systems: 6.8 compared with
      11.5 seconds (P = 0.006). However, the EPR with the shortest coding time had a
      longer prescribing time: 27.5 compared with 23.7 seconds (P = 0.64). CONCLUSION:
      This methodological development improves the reliability of our method for
      measuring the impact of different computer systems on the GP consultation. UAR
      added more objectivity to the observation of doctor-computer interactions. If
      larger studies were to reproduce the differences between computer systems
      demonstrated in this pilot it might be possible to make objective comparisons
      between systems.

PMID- 18713529
TI  - Readiness for electronic health records: comparison of characteristics of
      practices in a collaborative with the remainder of Massachusetts.
AB  - OBJECTIVE: The Massachusetts e-Health Collaborative (MAeHC) is implementing
      electronic health records (EHRs) in physicians' offices throughout three diverse
      communities. This study's objective was to assess the degree to which these
      practices are representative of physicians' practices statewide. DESIGN: We
      surveyed all MAeHC physicians (n=464) and compared their responses to those of a
      contemporaneously surveyed statewide random sample (n=1884). MEASUREMENTS: The
      survey questionnaire assessed practice characteristics related to EHR adoption,
      prevailing office culture related to quality and safety, attitudes toward health
      information technology (HIT) and perceptions of medical practice. RESULTS: A
      total of 355 MAeHC physicians (77%) and 1345 physicians from the statewide sample
      (71%) completed the survey. MAeHC practices resembled practices throughout
      Massachusetts in terms of practice size, physician age and gender, prevailing
      financial incentives for quality performance and HIT adoption and available
      resources for practice expansion. MAeHC practices were more likely to be located
      in rural areas (9.5% vs 4.4%, P=0.004). Physicians in both samples responded
      similarly to six of seven self-assessments of the office practice environment for
      quality and safety. Internet connections were more prevalent among MAeHC
      practices than across the state (96% vs 83%, P<0.001), but similar proportions of
      MAeHC physicians (83%) and statewide physicians (86%) used the internet daily
      (P=0.19). CONCLUSION: MAeHC is implementing EHRs and health information exchange
      among communities with physicians and practices that appear generally
      representative of Massachusetts. The lessons learned from this pilot project
      should be applicable statewide and to other states with large numbers of
      physicians in small office practices.

PMID- 18713530
TI  - The role of the electronic medical record (EMR) in care delivery development in
      developing countries: a systematic review.
AB  - OBJECTIVE: Most countries in Europe and the USA are increasingly using an
      electronic medical record (EMR) to help improve healthcare quality.
      Unfortunately, most developing countries face many challenges ranging from
      epidemics and civil wars to disasters: they also lack a robust healthcare
      infrastructure in the form of information and communications technology (ICT) to
      ensure continuity of patient health which many research studies consider a
      lifesaving resource. The aim of this systematic review is to examine the benefits
      of an EMR and its contribution to the development of healthcare delivery in
      developing countries. METHODS: We searched MEDLINE, PubMed, CINAHL, COMPENDEX and
      Academic Search Premier as well as systematically searching the reference lists
      of included studies and relevant reviews. Inclusion criteria were that studies
      should relate to the importance and challenges of an EMR system, paper-based
      medical records, development and implementation of an EMR system in developing
      countries or EMR impact on care delivery in developing countries. RESULTS: A
      total of 23 articles were identified that met the eligibility criteria. Articles
      identified were grouped into five non-exclusive areas: EMR benefits (n=4),
      challenges (n=6), transition from paper-based to EMR (n=5), EMR in developing
      countries (n=8) and pilot projects (n=5). Nine articles were excluded because
      three were not published in English and six were studies on EMR in developed
      countries. CONCLUSIONS: The potential of EMR systems to transform medical care
      practice has been recognised over the past decades, including the enhancement of
      healthcare delivery and facilitation of decision-making processes. Some benefits
      of an EMR system include accurate medication lists, legible notes and
      prescriptions and immediately available charts. In spite of challenges facing the
      developing world such as lack of human expertise and financial resource, most
      studies have shown how feasible it could be with support from developed nations
      to design and implement an EMR system that fits into this environment.

PMID- 18713531
TI  - Design and implementation of a web-based patient portal linked to an electronic
      health record designed to improve medication safety: the Patient Gateway
      medications module.
AB  - In this article we describe the background, design, and preliminary results of a
      medications module within Patient Gateway (PG), a patient portal linked to an
      electronic health record (EHR). The medications module is designed to improve the
      accuracy of medication lists within the EHR, reduce adverse drug events and
      improve patient-provider communication regarding medications and allergies in
      several primary care practices within a large integrated healthcare delivery
      network. This module allows patients to view and modify the list of medications
      and allergies from the EHR, report non-adherence, side effects and other
      medication-related problems and easily communicate this information to providers,
      who can verify the information and update the EHR as needed. Usage and
      satisfaction data indicate that patients found the module easy to use, felt that
      it led to their providers having more accurate information about them and enabled
      them to feel more prepared for their forthcoming visits. Further analyses will
      determine the effects of this module on important medication-related outcomes and
      identify further enhancements needed to improve on this approach.

PMID- 18713532
TI  - The Single Shared Electronic Patient Record (SSEPR): problems with functionality
      and governance.

PMID- 18713534
TI  - [Recognizing psychiatric comorbidity is an essential part of comprehensive
      diagnosis in medicine].

PMID- 18713535
TI  - [A dimensional diagnostic approach using the "Assessment of DSM-IV Personality
      Disorders (ADP-IV)" Questionnaire].
AB  - OBJECTIVES: The ADP-IV is a self-assessment instrument of personality disorders
      providing categorical as well as dimensional diagnoses. The German translation of
      the Dutch original has already shown sufficient reliability as well as a rather
      weak convergent validity of categorical diagnoses. This study investigates the
      validity of the dimensional assessment of personality disorders. METHODS: Four
      hundred patients and a community sample of 385 subjects completed the ADP-IV. A
      SCID-II interview and an expert consensus rating were also performed in 210
      patients. Norms for patients and the community sample were calculated by using z
      transformation. Receiver operator curves (ROC) were employed for the
      determination of cut-offs for categorical diagnoses on the basis of the
      dimensional scores. RESULTS: The ROC analyses resulted in negative predictive
      values of 99 % for the five most frequent personality disorders in the sample; in
      contrast, positive predictive values were low. CONCLUSIONS: The instrument is
      well suited for screening purposes, allowing for a reliable exclusion of
      personality disorders. For diagnosing personality disorders, however, clinical
      interviewing remains necessary. Norms and a dimensional personality disorder
      profile provide hints concerning the presence of pathological personality traits
      with respect to the reference group. The ADP-IV represents the only German
      language questionnaire for the assessment of DSM-IV personality disorders which
      has been sufficiently validated. It is freely available on the internet at
      http://zmkweb.uni
      muenster.de/einrichtungen/proth/dienstleistungen/psycho/diag/index.html.

PMID- 18713536
TI  - [The relationship between tinnitus, personality, and depression].
AB  - OBJECTIVE: This study examines the relationship between personality
      characteristics, depression symptoms, demographic profile, and the amount of the
      tinnitus-related distress experienced. METHOD: 121 patients suffering from
      tinnitus were examined by unique testing in a tinnitus-practice via three
      questionnaires over a period of 22 months. RESULTS: A relationship between the
      severity of tinnitus-related distress and demographic profile as well as a
      relationship between depression symptoms and the severity of the tinnitus-related
      distress could be shown. Also, significant results were observed within the
      personality range in the areas of "impulsiveness," "aggressiveness," "demands,"
      "physical discomfort," "health worries," und "emotionality." DISCUSSION: Patients
      suffering severely from tinnitus represent a clinically relevant group for
      psychotherapeutic treatment. Especially persons with comorbid symptoms of
      depression should be screened regularly and offered additional psychotherapeutic
      or psychiatric treatment.

PMID- 18713537
TI  - [Dropout behavior in inpatient psychosomatic rehabilitation: how and when do
      inpatients terminate psychotherapy?].
AB  - Despite its clinical and health economic importance, only few studies have
      analyzed the problem of dropout behavior from treatment in psychosomatic medicine
      and psychotherapy. For quality-assurance purposes and in light of limited
      resources in our medical system, it is important to identify future dropouts and
      to intervene appropriately during ongoing inpatient treatment. In a
      representative sample taken from inpatient psychosomatic rehabilitation, we
      evaluated the prevalence of dropout behavior as well as characteristics of
      patients who drop out compared to patients who complete the treatment regularly.
      OBJECTIVES: Data of 2059 inpatients from the Psychosomatic Hospital Bad
      Neustadt/Saale were analyzed as to rates and dates of dropout and other patient
      characteristics. RESULTS: Overall 15.7 % of the patients dropped out of inpatient
      psychosomatic rehabilitation after a mean treatment duration of 28 days. Patients
      who dropped out tended to be younger, reported less distress, were less
      motivated, and had been diagnosed less often with an affective disorder as main
      diagnosis. Compared with patients who completed therapy regularly, they also
      profited less from both self- as well as external assessment of symptom change.
      It was shown that it is useful to differentiate the method and time of dropout.
      CONCLUSIONS: A differentiation of dropout characteristics is important for
      developing interventions to reduce dropout rates.

PMID- 18713538
TI  - [Effects of anxiety self-help groups in the view of patients and experts].
AB  - OBJECTIVES: This study assesses the development of patients with anxiety
      disorders in self-help groups. An additional investigation studies the attitude
      of psychotherapists toward such self-help groups. METHODS: 33 participants from
      three self-help groups were assessed using nonstandardised and standardised
      questionnaires (SCL-90-R, STAI). In addition, 250 psychotherapists were surveyed.
      RESULTS: Subjectively, the patients experienced their group as being helpful and
      described their symptoms as having slightly improved. The patients showed high
      scores in the anxiety questionnaire, which marginally improved over time.
      Avoiding behaviour did not change. The patients showed small improvements on some
      SCL scales (compulsiveness, aggressiveness, phobia, psychoticism). More than 80 %
      of the psychotherapists studied share the opinion that a self-help group can
      indeed support the course of a psychotherapeutic treatment. DISCUSSION: Self-help
      groups are effective from the view of both the patients and the psychotherapists.
      Yet, most patients studied continued to show high scores of anxiety and
      psychopathology.

PMID- 18713539
TI  - [Childhood-onset versus acute, adult-onset traumatized patients in the light of
      amnestic tendencies and derealisation].
AB  - OBJECTIVES: In the present study we examined the facial affective behaviour of
      acute adult-onset traumatized patients versus childhood-onset traumatized
      patients. Furthermore, we analyzed whether a decrease in emotional numbing
      results from a reduction of symptoms. We used amnestic tendencies as a moderator
      variable. METHODS: The facial affective behaviour was coded with the Emotional
      Facial Acting Coding System, an instrument for the registration of facial
      movements with emotional relevance. The facial affective behaviour of the
      patient's first and last EMDR sessions was compared. RESULTS: Childhood-onset and
      acute adult-onset traumatized patients showed the same reduction of overall
      facial activity. We found significantly higher psychic complaints (global
      severity index) (SCL-90-R) in childhood-onset traumatized patients and no
      difference in amnestic tendencies (FDS) between the two groups. Childhood-onset
      traumatized patients showed higher values of derealisation (FDS). CONCLUSIONS:
      The facial affective reduction remains constant over time. Also childhood-onset
      traumatized patients developed more psychic complaints and greater derealisation.

PMID- 18713540
TI  - [Success of referral in a psychosomatic-psychotherapeutic outpatient unit of a
      dental school].
AB  - OBJECTIVES: The success of referral for psychotherapy and the predictors thereof
      are investigated in dentistry in an outpatient unit for psychosomatics. METHODS:
      238 patients were asked in a telephone interview concerning their satisfaction
      with the consultation as well as any change in their complaints and treatments
      after their contact with the outpatient unit. RESULTS: 82.3 % of the patients
      were satisfied with the consultation, and 55.9 % reported an improvement in their
      complaints. In 76.1 % of the patients psychotherapy was indicated, and 56.7 %
      showed motivation and were referred to psychotherapy. Thereof, 66.7 % actually
      began treatment. Introspective capacity and motivation for psychotherapy
      predicted successful referral. Patients suffering from somatoform disorders were
      significantly less motivated to begin psychotherapy and showed a tendency toward
      premature termination of psychotherapy. In patients with anxiety disorders, the
      reverse was the case. Patients who did not begin psychotherapy changed their
      dentist significantly more frequently. CONCLUSIONS: The consultation at the
      outpatient unit can be regarded as successful insofar as four-fifths of the
      patients were satisfied and two-thirds of those referred actually began
      psychotherapy, which in turn significantly reduces "dentist shopping."

PMID- 18713542
TI  - Prognostic values of serum cystatin C and beta2 microglobulin, urinary beta2
      microglobulin and N-acetyl-beta-D-glucosaminidase in early acute renal failure
      after liver transplantation.
AB  - BACKGROUND: Acute renal failure (ARF) after liver transplantation is associated
      with high mortality and morbidity. Early therapeutic or preventive intervention
      is hampered by the lack of early effective prognostic factors. Recent studies
      indicated that serum levels of cystatin C and beta2-microglobulin (beta2 MG) as
      well as urinary beta2 MG and N-acetyl-beta-D-glucosaminidase (NAG) would increase
      in patients with early and mild renal impairment. In this study, these factors
      were detected during the different stages in patients who accepted orthotopic
      liver transplantation (OLT), and their feasibilities to predict early ARF after
      OLT were also analyzed. METHODS: Sixty patients with normal blood urea nitrogen
      (BUN) and serum creatinine (SCr) who received modified piggyback liver
      transplantation without veno-venous bypass were prospectively studied. Blood
      samples were drawn from patients for the determination of serum beta2 MG (n =
      60), SCr (n = 60) and serum Cystatin C (n = 39) at following 5 intervals: before
      operation (T0), 20 minutes before anhepatic phase (T1), 25 minutes in anhepatic
      (T2), 60 minutes after reperfusion (T3) and at the end of operation (T4). Urinary
      beta2 MG (n = 60) and NAG (n = 60) were also examined at following 3 intervals:
      before operation (T0), 60 minutes after reperfusion (T3) and at the end of
      operation (T4). According to the Rimola A criteria of ARF in 24 hours after
      operation, all the patients were divided into two groups: ARF group and non-ARF
      group. The data were statistically analyzed to evaluate the feasibiliy of
      regarding these factors as prognostic factors for early ARF after liver
      transplantation in patients with normal SCr and BUN before operation. RESULTS:
      Ten of sixty cases showed ARF (16.7%). The Logistic regression analysis showed
      that the levels of serum and urinary beta2 MG as well as serum cystatin C before
      operation were correlated with early ARF after liver transplantation (P < 0.05),
      while only serum levels of cystatin C and Cr at the end of operation correlated
      with early ARF (P < 0.05, P < 0.01) after liver transplantation. The serum beta2
      MG, Cystatin C, SCr and urinary beta2 MG levels in ARF group were much more
      higher than that in non-ARF group (P < 0.05, P < 0.01). There were significant
      differences between the correct and false predictive positive ratios of serum
      cystatin C, serum and urinary beta2 MG levels before operation (P < 0.05, P <
      0.01), while only SCr showed significant difference between these groups at the
      end of operation (P < 0.01). CONCLUSIONS: The results revealed that there was
      potential renal damage among those patients who demonstrated normal SCr and BUN
      before operation, and that liver transplantation could aggravate this damage and
      causing ARF. Here we provided the prognostic values of serum Cystatin C, beta2
      MG, urinary beta2 MG and NAG in patients with early acute renal failure after
      liver transplantation.

PMID- 18713543
TI  - Microarray-bioinformatics analysis of altered genomic expression profiles between
      human fetal and infant myocardium.
AB  - BACKGROUND: The physiological differences between fetal and postnatal heart have
      been well characterized at the cellular level. However, the genetic mechanisms
      governing and regulating these differences have only been partially elucidated.
      Elucidation of the differentially expressed genes profile before and after birth
      has never been systematically proposed and analyzed. METHODS: The human
      oligonucleotide microarray and bioinformatics analysis approaches were applied to
      isolate and classify the differentially expressed genes between fetal and infant
      cardiac tissue samples. Quantitative real-time PCR was used to confirm the
      results from the microarray. RESULTS: Two hundred and forty-two differentially
      expressed genes were discovered and classified into 13 categories, including
      genes related to energy metabolism, myocyte hyperplasia, development, muscle
      contraction, protein synthesis and degradation, extracellular matrix components,
      transcription factors, apoptosis, signal pathway molecules, organelle
      organization and several other biological processes. Moreover, 95 genes were
      identified which had not previously been reported to be expressed in the heart.
      CONCLUSIONS: The study systematically analyzed the alteration of the gene
      expression profile between the human fetal and infant myocardium. A number of
      genes were discovered which had not been reported to be expressed in the heart.
      The data provided insight into the physical development mechanisms of the heart
      before and after birth.

PMID- 18713544
TI  - Clinical features and hMSH2/hMLH1 germ-line mutations in Chinese patients with
      hereditary nonpolyposis colorectal cancer.
AB  - BACKGROUND: At least five mismatch repair (MMR) genes, including hMSH2, hMLH1,
      hPMS, hPMS2, and hMSH6/GTBP, are associated with hereditary nonpolyposis
      colorectal cancer (HNPCC). More than 90% of families with HNPCC harbor the hMSH2
      and hMLH1 gene mutations. We have analyzed the clinical features of HNPCC among
      Chinese patients and report the results of screening for mutations in the hMSH2
      and hMLH1 genes. METHODS: The data concerning gender, site of colorectal cancer
      (CRC), age at diagnosis, history of synchronous and/or metachronous colorectal
      cancer, instance of extracolonic cancers, and histopathology of tumors for 126
      patients from 28 independent families with HNPCC were collected. Fifteen of the
      families met the Amsterdam I criteria, and 13 met the Japanese clinical criteria
      for diagnosis. Genomic DNA was extracted from the peripheral lymphocytes.
      Polymerase chain reaction (PCR) and denaturing high-performance liquid
      chromatography (DHPLC) were used to screen the coding region of the hMSH2 and
      hMLH1 genes. Samples showing abnormal DHPLC profiles were sequenced. RESULTS: One
      hundred and seventy malignant neoplasms were found in the 126 patients, of whom
      23 had multiple cancers. Ninety-eight of the patients (77.8%) had colorectal
      cancers, with an average age at onset of 45.9 years and a right-sided
      predominance. Eight hMSH2 or hMLH1 gene sequence variations were found in 12
      families, and a germ-line G204X nonsense mutation in the third exon of hMSH2 was
      found, representing the first mutation in an MMR gene ever found in people of
      Chinese Mongolian ethnicity. CONCLUSIONS: HNPCC is a typical autosomally dominant
      hereditary disease, characterized by early onset, a predominance of proximal
      colorectal cancer, and multiple synchronous and metachronous colorectal cancers.
      DHPLC is a powerful tool for detecting mutations in the hMSH2 and hMLH1 genes.
      Mutations in the first nine exons of the hMLH1 gene were more common in Chinese
      patients.

PMID- 18713545
TI  - Increased expression of heat shock protein 70 and heat shock factor 1 in chronic
      dermal ulcer tissues treated with laser-aided therapy.
AB  - BACKGROUND: Chronic dermal ulcers are also referred to as refractory ulcers. This
      study was conducted to elucidate the therapeutic effect of laser on chronic
      dermal ulcers and the induced expression of heat shock factor 1 (HSF1) and heat
      shock protein 70 (HSP70) in wound tissues. METHODS: Sixty patients with 84
      chronic dermal ulcers were randomly divided into traditional therapy and laser
      therapy groups. Laser treatment was performed in addition to traditional therapy
      in the laser therapy group. The treatment efficacy was evaluated after three
      weeks. Five tissue sections of healing wounds were randomly collected along with
      five normal skin sections as controls. HSP70-positive cells from HSP70
      immunohistochemical staining were counted and the gray scale of positive cells
      was measured for statistical analysis. Reverse transcription-polymerase chain
      reaction (RT-PCR) and Western blotting were performed to determine the mRNA and
      protein expressions of HSF1 and HSP70. RESULTS: The cure rate of the wounds and
      the total efficacy in the laser therapy group were significantly higher than
      those in the traditional therapy group (P < 0.05, P < 0.01, respectively).
      Immunohistochemical staining revealed that the HSP70-positive cell count was
      significantly higher in laser therapy group than those in the traditional therapy
      group and controls (P < 0.01), and the gray scale of the cell signal was
      obviously lower than traditional therapy group and controls (P < 0.05). By
      contrast, the traditional therapy group and the control group were not
      significantly different. The RNA levels of HSF1 and HSP70 were higher in the
      laser therapy group by RT-PCR, but very low in normal skin and the traditional
      therapy group. The analysis on the gray scale of the Western blot bands indicated
      that the expression of HSF1 and HSP70 in the laser therapy group was
      significantly higher than in the traditional therapy group and the control group
      (P < 0.01), and the expression in the traditional therapy group was also higher
      than in the control group (P < 0.05). CONCLUSION: Laser-aided therapy of chronic
      dermal ulcers plays a facilitating role in healing due to the mechanism of laser
      activated endogenous heat shock protection in cells in wound surfaces.

PMID- 18713546
TI  - Evaluating subconjunctival bleb function after trabeculectomy using slit-lamp
      optical coherence tomography and ultrasound biomicroscopy.
AB  - BACKGROUND: The existing classifications for evaluating glaucoma filtering blebs
      rely mostly on external bleb characteristics and the postoperative control of
      intraocular pressure (IOP). Internal bleb structures are not carefully observed.
      This study aimed to analyze and compare glaucoma filtering bleb morphology using
      slit-lamp-adapted optical coherence tomography (SL-OCT) and ultrasound
      biomicroscopy (UBM), and to classify blebs according to results and intraocular
      pressure. METHODS: We followed 29 eyes of 21 male patients and 40 eyes of 32
      female patients who underwent glaucoma filtering surgery in Sixth People's
      Hospital of Shanghai, between 2002 and 2006. The blebs were imaged using SL-OCT
      and UBM and classified according to the intrableb morphology and control of IOP
      after surgery. A Fisher's exact test was used to compare the sensitivity for
      predicting a functioning bleb differed significantly between SL-OCT and UBM. A
      Fisher's exact test was also used for morphological analysis of the
      trabeculectomy blebs based on SL-OCT. RESULTS: In the 69 eyes, there were 45
      (65.2%) functioning blebs and 24 (34.8%) non-functioning blebs. We classified the
      blebs into four categories on the basis of SL-OCT images: diffuse, cystic,
      encapsulated and flat. Diffuse and cystic blebs were typically functional,
      whereas the other two types were always non-functional. The sensitivity of SL-OCT
      for predicting a functioning bleb was 92.7% (38/41 eyes) and specificity of
      predicting a non-functioning bleb was 83.3% (20/24 eyes). By contrast,
      sensitivity of UBM was 66.7% (30/45 eyes) and specificity was 75.0% (18/24 eyes).
      The sensitivity for predicting a functioning bleb differed significantly between
      the two techniques (P = 0.003). CONCLUSIONS: SL-OCT provides high-axial
      resolution images of anterior segment structures. The non-contact approach of SL
      OCT enables visualization of intrableb structures at any time after surgery. SL
      OCT has greater sensitivity and specificity than UBM in evaluating filtering bleb
      function. The morphological classification supported the assessment of bleb
      function and could provide objective data for evaluating the outcome of
      antiglaucoma surgery or the need for a second procedure.

PMID- 18713548
TI  - Salmon calcitonin in prevention of osteoporosis in maintenance dialysis patients.
AB  - BACKGROUND: Renal osteodystrophy is one of the commonest complications of chronic
      renal failure. It may have a severe impact on the quality of life of patients on
      maintenance dialysis therapy. Besides post-menopausal women and elderly people,
      the dialysis patients are another high risk group. But at present, there is no
      research on how to prevent osteoporosis in maintenance dialysis patients. This
      study was conducted to observe the bone density of maintenance dialysis patients
      and to evaluate the clinical outcomes and safety of different administration
      dosage of salmon calcitonin to prevent osteoporosis in maintenance dialysis
      patients. METHODS: One hundred and forty-eight patients on maintenance dialysis
      were involved in the 12-month, randomized, controlled trial. Fifty patients
      (experiment I group) received subcutaneous injection of salmon calcitonin (50 U)
      three times a week for 12 months. Fifty patients (experiment II group) received
      subcutaneous injection of salmon calcitonin (100 U) three times a week for 12
      months. At the same time, both of them received oral calcium carbonate 1500 mg
      tid and rocaltrol 0.25 microg qn for 12 months. The control group only received
      oral calcium carbonate 1500 mg tid and rocaltrol 0.25 microg qn for 12 months.
      The levels of bone mass density (BMD) of the lumbar spine and femoral neck, serum
      intact parathyroid hormone (iPTH), osteocalcin (OC), calcium, phosphorus,
      alkaline phosphatase (ALP) were assessed at baseline and then again after 3, 6
      and 12 months of treatment. RESULTS: The values of BMD at the lumbar spine and
      femoral neck before the treatment were not significantly different from those 3,
      6, and 12 months after the treatment in trial groups I and II (all P > 0.05) and
      there were no significant differences in the BMD values at different time points
      between trial groups I and II. In the control group, the BMD values at the lumbar
      spine and femoral neck 3, 6, and 12 months after the beginning of trial were
      significantly lower than those before the trial, and significantly lower than the
      corresponding values of trial groups I and II (all P < 0.05). The serum OC 3, 6,
      and 12 months after the treatment was significantly lower than that before the
      experiment (all P < 0.05) in the control group. However, there was no significant
      difference in the value of serum OC before and 3, 6, and 12 months after the
      treatment in trial groups I and II (all P > 0.05). CONCLUSIONS: The dose of
      salmon calcitonin 50 U three times a week plus calcium carbonate and active
      vitamin D can effectively preserve the BMD and prevent bone loss in maintenance
      dialysis patients, and it is well tolerated by patients on maintenance dialysis.

PMID- 18713549
TI  - Colonoscopy in the diagnosis of intestinal graft versus host disease and
      cytomegalovirus enteritis following allogeneic haematopoietic stem cell
      transplantation.
AB  - BACKGROUND: Gastrointestinal graft versus host disease (GI-GVHD) and
      cytomegalovirus (CMV) enteritis are important complications following allogeneic
      haematopoietic stem cell transplantation (allo-HSCT). We explored the role of
      colonoscopy in the diagnosis of GI-GVHD and CMV enteritis following allo-HSCT to
      identify the endoscopic manifestations of GI-GVHD and CMV enteritis was made.
      METHODS: A retrospective analysis of the colonoscopic manifestations of GI-GVHD,
      CMV enteritis and GI-GVHD with concurrent CMV enteritis (GconC) and their related
      clinical issues. RESULTS: Forty-seven patients underwent 50 colonoscopies with
      diagnoses of 32 GI-GVHD, 7 CMV enteritis and 11 GconC. Both GI-GVHD and CMV
      enteritis had colonic mucosal lesions with various manifestations under
      colonoscopy. Tortoise shell like changes of the mucosa (12 of 32) and deep ulcers
      (2 of 7) were specific endoscopic manifestations for GI-GVHD and CMV enteritis,
      respectively, while mucosal oedema, erythema, congestion, erosion and shallow
      ulcers could not be used to differentiate GI-GVHD from CMV enteritis. GconC
      patients were prone to have oozing bleeding of the end ileal mucosa and
      typhlodicliditis. Of the biopsed specimens for GI-GVHD, CMV enteritis and GconC,
      64%, 70% and 44% were taken from the rectum and sigmoid colon respectively.
      CONCLUSIONS: Following allo-HSCT, tortoise shell like changes and deep ulcers of
      the colonic mucosa are characteristic changes for GI-GVHD and CMV enteritis,
      respectively, while the other lesions are not. Most of the GI-GVHDs and CMV
      enteritis cases can be diagnosed by left colon examination and tissue biopsy, but
      total colon examination to the terminal ileum is preferred.

PMID- 18713550
TI  - Circulatory responses to nasotracheal intubation: comparison of GlideScope
      videolaryngoscope and Macintosh direct laryngoscope.
AB  - BACKGROUND: The GlideScope videolaryngoscope (GSVL) has been shown to have no
      special advantage over the Macintosh direct laryngoscope (MDL) in attenuating the
      circulatory responses to orotracheal intubation, but no study has compared the
      circulatory responses to nasotracheal intubation (NTI) using the two devices.
      This prospective randomized clinical study was designed to determine whether
      there was a clinically relevant difference between the circulatory responses to
      NTI with the GSVL and the MDL. METHODS: Seventy-six adult patients were randomly
      allocated equally to the GSVL group and the MDL group. After induction of
      anesthesia, NTI was performed. Non-invasive blood pressure (BP) and heart rate
      (HR) were recorded before induction (baseline values) and immediately before
      intubation (post-induction values), at intubation and every minute for a further
      five minutes. During the observation, times required to reach the maximum values
      of systolic BP (SBP) and HR, times required for recovery of SBP and HR to
      postinduction values and incidence of SBP and HR percent changes > 30% of
      baseline values were also noted. The product of HR and systolic BP, i.e. rate
      pressure product (RPP), and the areas under SBP and HR vs. time curves (AUC(SBP)
      and AUC(HR)) were calculated. RESULTS: The NTI with the GSVL resulted in
      significant increases in BP, HR and RPP compared to postinduction values, but
      these circulatory changes did not exceed baseline values. BPs at all measuring
      points, AUC(SBP), maximum values of BP and incidence of SBP percent increase >
      30% of baseline value during the observation did not differ significantly between
      groups. However, HR and RPP at intubation and their maximum values, AUC(HR) and
      incidence of HR percent increase > 30% of baseline value were significantly
      higher in the MDL group than in the GSVL group. Times required for recovery of
      SBP and HR to postinduction values were significantly longer in the MDL group
      than in the GSVL group. CONCLUSIONS: The pressor response to NTI with the GSVL
      and the MDL was similar, but the tachycardiac response to NTI was lesser and of a
      shorter duration when using a GSVL than when using an MDL.

PMID- 18713551
TI  - Dilated intercellular spaces in gastroesophageal reflux disease patients and the
      changes of intercellular spaces after omeprazole treatment.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disorder. Dilation
      of intercellular spaces of esophageal epithelium has been revealed at
      transmission electron microscopy both in the rabbit acid-perfused esophagus and
      in esophageal biopsies from GERD patients. This study aimed to observe the
      changes of the intercellular spaces of squamous epithelium of lower esophagus in
      patients with GERD and the changes of intercellular spaces of patients with
      erosive esophagitis (EE) before and after omeprazole treatment. METHODS:
      Outpatients having GERD symptoms for more than 3 months and volunteers were
      collected. All of them underwent gastroendoscopy and 24-hour ambulatory pH
      monitoring. Biopsies were taken from the lower esophagus (2 cm above Z-line) for
      electron microscope examination. Five healthy volunteers, six non-erosive reflux
      disease (NERD) patients, and five EE patients were enrolled. Intercellular spaces
      of GERD patients and controls were calculated. Then we selected 20 patients with
      EE diagnosed by gastroendoscopy. All of them were treated with omeprazole (Losec,
      20 mg bid) for 4 weeks then underwent gastroendoscopy again. Biopsies were taken
      from 2 cm above Z-line for electron microscope examination. All the patients
      completed the questionnaire about reflux symptoms before and after treatment.
      RESULTS: Intercellular spaces of esophageal epithelial cell in volunteers, NERD
      patients and EE patients were (0.37 +/- 0.07) microm, (1.31 +/- 0.08) microm, and
      (1.33 +/- 0.14) microm, respectively, with significant differences between the
      control group and the NERD group (P = 0.000). In the 20 EE patients, the mean
      intercellular space before treatment was (1.14 +/- 0.15) microm. After treatment
      the intercellular space was (0.51 +/- 0.18) microm, a significant difference
      compared with pre-treatment measurements (P = 0.000). CONCLUSIONS: Dilated
      intercellular spaces (DIS) were seen in both NERD and EE cases. The dilated
      intercellular spaces of esophageal epithelium in EE patients could be recovered
      after a short time of treatment with omeprazole.

PMID- 18713552
TI  - Effects of portal venous arterialization on acute occlusion of hepatic artery in
      rats.
AB  - BACKGROUND: A fatal complication after liver transplantation is anastomotic
      embolization of the hepatic artery. In order to solve this problem, the portal
      venous arterialization (PVA) is used to reconstruct the hepatic arterial blood
      flow. The purpose of this study was to investigate the influence of PVA on rats
      with acute occlusion of hepatic artery. METHODS: Rat PVA models were established
      and then randomly divided into Group 1 (control group), Group 2 (jaundice group),
      Group 3 (bile duct recanalization group), and Group 4 (portal vein arterilization
      group). Recanalization of the common bile duct and PVA were performed 5 days
      after bile duct ligation in the rats. The influence of the PVA on general
      conditions, hepatic changes of structure and function, portal vein pressure and
      hepatic micrangium were observed for one month. RESULTS: Five days after common
      bile duct ligation the serum bilirubin, transaminase and alkaline phosphatase
      levels were significantly increased. Compared with group 1, there was a
      statistically significant difference (P < 0.01). These rats then underwent bile
      duct recanalization and PVA. After a month, the liver functions and microscopic
      structures completely returned to normal and, compared with group 1, there was no
      statistically significant difference in portal vein pressure (P > 0.05). Vascular
      casting samples showed that hepatic sinusoids were slightly thicker and more
      filled than normal ones and although they had some deformations, the hepatic
      sinusoids were still distributed around the central vein in radial form.
      CONCLUSION: Within a month after operation, bile duct recanalization and PVA do
      not show obvious adverse effects on liver hemodynamics and hepatic micrangium,
      and the liver function and microscopic structure can return to normal.

PMID- 18713553
TI  - Effects of repetitive transcranial magnetic stimulation on adenosine triphosphate
      content and microtubule associated protein-2 expression after cerebral ischemia
      reperfusion injury in rat brain.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) research has
      mainly been focused on the therapeutic effect of psychiatric disorders and
      Parkinson's disease. A few studies have shown that rTMS might protect against
      delayed neuronal death induced by transient ischemia, enhance long-term
      potentiation in ischemic conditions and affect regional brain blood flow and
      metabolism. The aim of this study was to determine the effects of repetitive
      transcranial magnetic stimulation (rTMS) on adenosine triphosphate (ATP) content
      and microtubule associated protein-2 (MAP-2) expression in rat brain after middle
      cerebral artery occlusion (MCAO)/reperfusion. METHODS: To study the effects of
      different timecourses of rTMS on ATP content and MAP-2 expression, 90 rats were
      randomly divided into three groups (30 rats in each group). To study the effects
      of multiple rTMS parameters on ATP content and MAP-2 expression, the rats in each
      group were further divided into six subgroups (five rats each). The rats were
      sacrificed at 1-hour, 24-hour and 48-hour intervals after reperfusion, and the
      brain tissues were collected for the detection of ATP and MAP-2. RESULTS: rTMS
      could significantly increase ATP content and MAP-2 expression in the left brain
      following ischemic insult (P < 0.01) and different rTMS parameters had different
      effects on the ATP level and the MAP-2 expression in the left striatum. A high
      frequency rTMS played an important role in MAP-2 expression and ATP preservation.
      CONCLUSIONS: This study revealed that rTMS induced significant increase of ATP
      content and MAP-2 expression in the injured area of the brain, suggesting that
      the regulation of both ATP and MAP-2 may be involved in the biological mechanism
      of the effect of rTMS on neural recovery. Therefore, rTMS may become a potential
      adjunctive therapy for ischemic cerebrovascular disease.

PMID- 18713554
TI  - Anti-apoptotic effect of morphine-induced delayed preconditioning on pulmonary
      artery endothelial cells with anoxia/reoxygenation injury.
AB  - BACKGROUND: Opioid preconditioning (PC) reduces anoxia/reoxygenation (A/R) injury
      to various cells. However, it remains unclear whether opioid-induced delayed PC
      would show anti-apoptotic effects on pulmonary artery endothelial cells (PAECs)
      suffering from A/R injury. The present study was conducted to elucidate this
      issue and to investigate the potential mechanism of opioid-induced delayed PC.
      METHODS: Cultured porcine PAECs underwent 16-hour anoxia followed by 1-hour
      reoxygenation 24 hours after pretreatment with saline (NaCl; 0.9%) or morphine (1
      micromol/L). To determine the underlying mechanism, a non-selective K(ATP)
      channel inhibitor glibenclamide (Glib; 10 micromol/L), a nitric oxide (NO)
      synthase blocker NG-nitro-L-arginine methyl ester (L-NAME; 100 micromol/L), and
      an opioid receptor antagonist naloxone (Nal; 10 micromol/L) were given 30 minutes
      before the A/R load. The percentage of apoptotic cells was assessed by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.
      eNOS mRNA level was measured by real-time polymerase chain reaction (PCR). NO
      content of PAECs supernatants was measured with the Griess reagent. RESULTS:
      Compared to the A/R PAECs, morphine-induced delayed PC significantly reduced
      PAECs apoptosis ((18.1 +/- 1.9)% vs (5.5 +/- 0.3)%; P < 0.05), increased NO
      release ((11.4 +/- 1.3) micromol/L vs (20.5 +/- 2.1) micromol/L, P < 0.05), and
      up-regulated eNOS gene expression nearly 9 times (P < 0.05). The anti-apoptosis
      effect of morphine was abolished by pretreatment with Glib, L-NAME and Nal, but
      the three agent-selves did not aggravate the A/R injury. Furthermore, L-NAME and
      Nal offset the enhanced release of NO caused by pretreatment with morphine.
      CONCLUSIONS: Morphine-induced delayed PC prevents A/R injury of PAECs. This
      effect may be mediated by activation of K(ATP) channel via opioid receptor and NO
      signaling pathways.

PMID- 18713555
TI  - B lymphocyte stimulator: a new target for treating B cell malignancies.

PMID- 18713556
TI  - Comparison of endotracheal intubation with the Shikani Optical Stylet using the
      left molar approach and direct laryngoscopy.

PMID- 18713557
TI  - Primary obturator foramen pregnancy: a case report and review of literature.

PMID- 18713558
TI  - Comparing models of mental health service systems between Australia and China:
      implications for the future development of Chinese mental health service.

PMID- 18713559
TI  - A mobile mass--a left atrial undifferentiated sarcoma mimicking myxoma: a case
      report.

PMID- 18713560
TI  - Transcatheter coil embolization of multiple coronary artery-to-left ventricle
      fistulas: report of a rare case.

PMID- 18713561
TI  - Health ministry warns of iodine deficiency in part of China.

PMID- 18713562
TI  - MS in Latin America.

PMID- 18713563
TI  - MS in Latin America.
AB  - During the last few years, there has been an increasing desire to study and
      expand current knowledge about the different aspects of Multiple Sclerosis (MS)
      in Latin America (LATAM). This report analyzes epidemiological data and specific
      aspects of MS in this region and aims to describe the current situation, based on
      the very few scientific publications that contain reliable information.
      Everything seems to indicate that MS in LATAM has some special characteristics
      that makes it different from what has been described in other areas of the world.
      Nevertheless, more thorough research has to be carried out in order to obtain
      conclusive data regarding the behaviour of the disease in LATAM.

PMID- 18713564
TI  - Spotlight on fumarates.
AB  - The recent years have witnessed great efforts in establishing new therapeutic
      options for multiple sclerosis (MS). There is a clear need for more effective,
      safe and at the same time orally available treatment options. Here we review the
      potential of fumaric acid esters (FAE) as a new therapeutic option for MS. FAE
      have been claimed to possess immunomodulatory properties and are already in
      clinical use as second-line therapy for severe systemic psoriasis. They also
      displayed beneficial effects in experimental autoimmune encephalomyelitis (EAE),
      a model mimicking many aspects of MS. In addition, FAE may also act on the blood
      brain barrier and exert neuroprotective properties via activation of anti
      oxidative pathways. A first magnetic resonance imaging (MRI) based Phase II study
      in relapsing-remitting MS (RRMS) revealed a dose-dependent, significant reduction
      of brain lesion activity for BG-12, a dimethyl FAE compound. Currently, two
      multicentre, Phase III studies for testing clinical efficacy in RRMS are
      initiated. In view of their profile, FAE compounds may have the potential to add
      to our therapeutic options in RRMS in the future.

PMID- 18713565
TI  - Spotlight on anti-CD20.
AB  - Immune modulators, such as interferon beta and glatiramer acetate, have focused
      on T-cells as the primary therapeutic target, although both drugs affect other
      cell types as well. There has been a renewed interest in the potential roles of
      both antibody-dependent and antibody-independent B-cell responses in multiple
      sclerosis (MS) and its animal model. Accumulating data suggest that the
      contribution of B-cells and their secreted products to central nervous system
      (CNS) inflammatory diseases may relate to the abilities of B-cells to (1)
      differentiate into plasmocytes that produce antibodies, (2) function as antigen
      presenting cells, contributing to Tcell activation, (3) produce effector
      cytokines that may modulate the local immune environment, (4) harbour the Epstein
      Barr virus in a chronically activated state, and (5) play a role in formation and
      maintenance of new lymphoid foci within the CNS. Understanding the biological and
      clinical impact of selective B-cell interventions such as rituximab (Rituxan,
      Genentech Inc., San Francisco, CA, USA) becomes of particular interest. This
      review will present the rational for B-cell based therapies in MS and related
      diseases and preliminary data suggesting a therapeutic benefit in MS and related
      diseases. In addition, other therapies aiming at CD20 will be reviewed.

PMID- 18713569
TI  - Novel therapeutic targets in neurodegenerative diseases: lessons from amyotrophic
      lateral sclerosis.

PMID- 18713570
TI  - Donepezil in patients with subcortical vascular cognitive impairment.

PMID- 18713571
TI  - Understanding hippocampal sclerosis in the elderly: epidemiology,
      characterization, and diagnostic issues.
AB  - Hippocampal sclerosis (HS) is a pathologic term used to describe severe loss of
      neurons and reactive gliosis without cystic cavitation in the CA1 sector of the
      hippocampus. In late life, HS is associated with hippocampal atrophy, severe
      amnesia, and slowly progressive dementia without clinical seizure activity. HS is
      difficult to distinguish clinically from Alzheimer's disease and is often
      diagnosed postmortem. In autopsy series, HS may be found without significant
      other pathology (2%-4% of cases), but it occurs frequently in combination with
      other vascular and neurodegenerative disorders (12%-20% of cases). HS is found
      bilaterally in 50% of cases and unilaterally in 50% of cases, with similar
      predilection for the right versus left hemisphere. The pathogenesis of HS is
      unknown and may be multifactorial in origin, possibly due to anoxic/ischemic
      injury or TDP-43-related neurodegeneration. Little is known about the prevention
      and treatment of late-life HS, although circumstantial evidence suggests the
      importance of identifying and treating vascular risk factors.

PMID- 18713572
TI  - Normal pressure hydrocephalus: diagnosis and treatment.
AB  - Normal pressure hydrocephalus (NPH) is a syndrome of gait dysfunction and
      enlarged cerebral ventricles in the absence of another cause. It is frequently
      accompanied by frontal and subcortical cognitive deficits and bladder detrusor
      overactivity. NPH is rare relative to other potential causes of these symptoms in
      the elderly, but timely diagnosis can lead to reversal of symptoms through
      ventricular shunting. There are many tests used to predict possible response to
      surgery, such as MRI of the brain, formalized neuropsychological and gait
      testing, large-volume lumbar puncture, and prolonged lumbar drainage, but no one
      test has been validated to rule out potential response to surgery.

PMID- 18713573
TI  - Driving and neurodegenerative diseases.
AB  - The proportion of elderly people in the general population is rising, resulting
      in greater numbers of drivers with neurodegenerative disorders such as
      Alzheimer's disease and Parkinson's disease. These neurodegenerative disorders
      impair cognition, visual perception, and motor function, leading to reduced
      driver fitness and greater crash risk. Yet neither medical diagnosis nor age
      alone is reliable enough to predict driver safety or crashes or to revoke the
      driving privileges of these individuals. Driving research utilizes tools such as
      questionnaires about driving habits and history, driving simulators, standardized
      road tests utilizing instrumented vehicles, and state driving records. Research
      challenges include outlining the evolution of driving safety, understanding the
      mechanisms of driving impairment, and developing a reliable and efficient
      standardized test battery for prediction of driver safety in neurodegenerative
      disorders. This information will enable healthcare providers to advise their
      patients with neurodegenerative disorders with more certainty, affect policy, and
      help develop rehabilitative measures for driving.

PMID- 18713574
TI  - The neuronal sortilin-related receptor gene SORL1 and late-onset Alzheimer's
      disease.
AB  - Recent studies indicate that two clusters of single nucleotide polymorphisms in
      the neuronal sortilin-related receptor gene (SORL1) are causally associated with
      late-onset Alzheimer's disease (AD). At the cellular level, SORL1 is thought to
      be involved in intracellular trafficking of amyloid precursor protein. When this
      gene is suppressed, toxic amyloid beta production is increased, and high levels
      of amyloid betaare associated with a higher AD risk. Extending the cellular
      findings, gene expression studies show that SORL1 is differentially expressed in
      AD patients compared with controls. Furthermore, several genetic studies have
      identified allelic and haplotypic SORL1 variants associated with late-onset AD,
      and these variants confer small to modest risk of AD. Taken together, the
      evidence for SORL1 as a causative gene is compelling. However, putative variants
      have not yet been identified. Further research is necessary to determine its
      utility as a diagnostic marker of AD or as a target for new therapeutic
      approaches.

PMID- 18713575
TI  - The syndrome of optic nerve hypoplasia.
AB  - The congenital malformation known as optic nerve hypoplasia (ONH) has been
      recognized in the past 30 years as an epidemic cause of congenital blindness. It
      was believed to occur either as an isolated anomaly or as a component of the
      syndrome of septo-optic dysplasia, which has evolved to include midline brain
      malformations and hypopituitarism. Evidence now suggests that ONH infrequently
      occurs in isolation. Most afflicted children will have hypothalamic dysfunction
      and/or neurodevelopmental impairment, regardless of MRI findings or severity of
      ONH. Adverse outcomes can often be ameliorated with early intervention. Thus, the
      syndrome of ONH should be suspected in all infants with signs of hypothalamic
      dysfunction or vision impairment.

PMID- 18713576
TI  - Drusen of the optic disc.
AB  - Optic disc drusen are acellular calcific deposits occurring in small, crowded
      optic discs with abnormal vasculature. Evidence suggests axoplasmic transport
      alteration and axonal degeneration are involved in disc drusen formation. In
      affected patients, the number and size of disc drusen are highly variable, and
      the drusen may be visible near the disc surface or buried within the disc,
      causing them to appear as pseudopapilledema. B-scan echography is the most
      sensitive method for detecting disc drusen. Most patients with disc drusen are
      asymptomatic, but progressive visual field loss and vascular complications,
      including anterior ischemic optic neuropathy and choroidal neovascularization,
      may occur. Optic disc drusen have no established effective treatment. Diagnosing
      disc drusen correctly is important to avoid unnecessary work-up and to avoid
      overlooking potential serious conditions such as true papilledema. Disc drusen
      patients with more-than-expected visual field defects or progressive visual loss
      should have work-up to exclude other causes.

PMID- 18713578
TI  - B-cell depletion with rituximab in relapsing-remitting multiple sclerosis.

PMID- 18713577
TI  - Cavitary anomalies of the optic disc: neurologic significance.
AB  - Cavitary congenital optic disc anomalies include optic disc coloboma, morning
      glory disc anomaly, optic pit, and the papillorenal syndrome. Peripapillary
      staphyloma is occasionally included in this group but it does not represent an
      anomaly of the optic disc itself and is not discussed herein. A variety of
      systemic and neurologic conditions may accompany these optic disc anomalies.
      Precise classification can be difficult and some debate exists as to whether
      these anomalies represent distinct clinical entities or are part of a single
      spectrum of disease. This is further complicated by historical inconsistencies in
      the literature. Advances in molecular genetics may help to define clearly the
      etiology of these anomalies.

PMID- 18713579
TI  - Monoclonal antibody treatments for multiple sclerosis.
AB  - Monoclonal antibodies (MAbs) may have great potential as therapies for autoimmune
      diseases. Their development as treatments for multiple sclerosis (MS) is
      promising. Partially effective immunomodulatory therapies have been helpful for
      many MS patients; however, for patients failing these immunomodulatory
      treatments, MAbs are an important new treatment option. Currently, MAbs are
      approved by the US Food and Drug Administration for treatment of many conditions,
      including autoimmune diseases. Four MAbs that have been investigated as potential
      treatments for MS are reviewed in this article. Of these MAbs, natalizumab is
      approved for treatment of MS. The other three MAbs (alemtuzumab, rituximab, and
      daclizumab) are all promising therapies in development for treatment of MS.
      Adverse effects are relatively mild for these MAbs; however, care in
      administration and management of these agents is emphasized. Overall, these MAb
      therapies have great promise in the treatment of MS.

PMID- 18713580
TI  - Neuromyelitis optica: diagnosis, pathogenesis, and treatment.
AB  - Although the co-occurrence of myelitis and optic neuritis that characterizes
      neuromyelitis optica (NMO) was recognized over a century ago, distinguishing NMO
      from multiple sclerosis relied solely on clinical criteria until recently. The
      identification of a biomarker that has high specificity for NMO is clinically
      useful for distinguishing NMO from multiple sclerosis and identifying patients at
      high risk for recurrent myelitis and optic neuritis. That fact that the biomarker
      is an autoantibody that recognizes aquaporin 4 (AQP4), a water channel expressed
      on astrocyte podocytes, has substantially contributed to the hypothesis that NMO
      is a humorally mediated autoimmune disease. This review discusses the discovery
      of the NMO-IgG biomarker, the identification of AQP4 as its target, the clinical
      applications of these advances, the pathologic implications for the anti-AQP4
      antibody, and advances in NMO treatment.

PMID- 18713582
TI  - Vector control in cutaneous leishmaniasis of the old world: a review of
      literature.
AB  - Cutaneous Leishmaniasis (CL), a disfiguring disease, is prevalent in many parts
      of Pakistan and neighboring Afghanistan. Leishmaniasis is second only to malaria
      in terms of the number of people affected; it is a major public health issue with
      significant social stigma. Although the different methods to diagnose and treat
      the disease are well discussed in the literature, the role of vector control in
      the prevention of CL has been underemphasized. Both Pubmed and Ovid search
      engines were used to obtain articles on prevention and control of cutaneous
      leishmaniasis. These materials were then screened for articles pertaining to
      vector control only. The World Health Organization's website along with the
      Cochrane database were also searched for relevant text. From this qualitative
      review, it can be seen that many effective interventions exist. Considering the
      multitude of factors involved in transmission of CL and the various effective
      control measures tried and tested by investigators, an interdisciplinary approach
      involving more than one of the above interventions would make sense. The
      interventions selected would then depend on the incidence of CL in that
      particular area, the population being targeted, the reservoir, the particular
      vector, the environment, the acceptability/popularity of the intervention, and
      the availability of funds.

PMID- 18713581
TI  - Pediatric multiple sclerosis.
AB  - Diagnosing multiple sclerosis (MS) in a child is challenging because of the
      limited diagnostic criteria and their overlap with acute disseminated
      encephalomyelitis. Pediatric-onset MS patients are more likely to be male, have
      seizures, and have brainstem and cerebellar symptoms than adults, and are less
      likely to have spinal cord symptoms than adults. They mostly experience a
      relapsing-remitting course. Their initial brain MRI shows more frequent
      involvement of the posterior fossa, less well-defined ovoid lesions, and more
      confluent lesions that decrease over time in patients with prepubertal onset,
      making early diagnosis even more difficult. Although disability progression is
      slower than in adults, pediatric onset MS leads to significant disability at a
      younger age and may be worse in non-white patients (up to 50% in North America).
      The rareness of pediatric-onset MS has precluded enrollment in clinical trials.
      Thus, children are receiving off-label adult therapies without clear evidence of
      their effectiveness and limited knowledge of their tolerability.

PMID- 18713583
TI  - Delusional disorders in dermatology: a brief review.
AB  - There are several unique psychiatric disorders that are likely to present to a
      dermatologist because of their accompanying skin complaints. Delusions of
      parasitosis (DP) is a fixed, false belief of parasitic infestation that may lead
      patients to compulsively self-mutilate while attempting to remove the non
      existent parasites. Morgellons disease is a controversial condition characterized
      by a fixed belief that fibers that are imbedded or extruding from the skin; this
      condition is likely in the spectrum of DP. Body dysmorphic disorder (BDD) is a
      preoccupation with an imagined defect in appearance that causes significant
      distress and is associated with time consuming rituals, isolation, depression,
      and increased risk of suicide. Olfactory reference syndrome (ORS) is a
      preoccupation with body odor leading to the stigmata of shame, embarrassment, and
      social isolation. This brief review examines each of these conditions and their
      management because any one of them may present to a dermatologist.

PMID- 18713584
TI  - Cutaneous metastatic adenocarcinoma arising from a malignant sacrococcygeal
      teratoma in an adult.
AB  - We present a patient with cutaneous metastasis caused by an adenocarcinoma
      arising from a malignant teratoma. A 37-year-old woman seen for the complaint of
      swelling in the genital region also complained of a draining mass in her gluteal
      region present since birth. Physical examination showed marked edema in the labia
      majora, multiple hyperkeratotic papules in the left labium majus, and erythema,
      induration, and swelling in the left femoral and inguinal regions. A soft tumor
      that exhibited sinus tracts was palpated in the left gluteus. Excision of the
      gluteal tumor revealed a teratoma. Vulvar skin biopsy confirmed a mucinous
      adenocarcinoma which had derived from this teratoma. A tumor that arises from
      pluripotent germ cells, teratoma rarely shows malignant transformation. The
      patient presented is a rare example of a cutaneous metastasis originating from a
      congenital sacrococcygeal teratoma in an adult.

PMID- 18713585
TI  - Report of a case: primary mucinous carcinoma of the skin.
AB  - Primary mucinous carcinoma of the skin is an extremely rare adnexal tumor that is
      thought to originate from eccrine sweat glands. The neoplasm usually arises on
      the head and neck, with the most commonly involved area being the periorbital
      region. The tumor is typically a solitary, asymptomatic nodule, cyst, or ulcer
      that is slow growing with low metastatic potential. However, post-excisional
      local recurrence is common, affecting up to 36 percent of patients. Since primary
      mucinous carcinoma of the skin is such a rare neoplasm (fewer than 130 cases have
      been reported to date), a complete workup should be conducted to rule out other
      internal malignancies that may metastasize to the skin. We report a case of
      primary mucinous carcinoma of the skin, and discuss the clinical presentation,
      histology, treatment, course, and prognosis.

PMID- 18713586
TI  - Invasive primary ductal apocrine adenocarcinoma of axilla: a case report with
      immunohistochemical profiling and a review of literature.
AB  - Primary cutaneous ductal apocrine adenocarcinoma (PCDAA) is a rare malignant
      cutaneous neoplasm usually arising in areas of high apocrine gland density. There
      have been a total of 40 cases of primary apocrine adenocarcinoma reported in the
      literature; many are indolent and slowly- developing, but some are rapidly
      progressive. Primary cutaneous ductal apocrine adenocarcinoma has distinctive
      histologic and immunohistochemical characteristics and the treatment of choice
      for PCDAA is wide local excision with clear margins. Sentinel lymph node biopsy
      (SLNB) has also been used to determine prognosis and management. We present a
      case of a 92-year-old female with a 1-year history of a subcutaneous tumor of the
      right axilla, histologically consistent with a diagnosis of PCDAA arising in an
      accessory nipple. To our knowledge this is the first reported case of apocrine
      adenocarcinoma to develop in an accessory nipple.

PMID- 18713587
TI  - Cutaneous myiasis arising in an eccrine adnexal neoplasm.
AB  - Myiasis is the infestation of human tissue by fly maggots. Although it is most
      often reported in tropical and sub-tropical regions of the world and in travelers
      returning from these areas, cases do occur in the United States. We report here a
      case of cutaneous myiasis observed in the setting of an eccrine adnexal neoplasm
      in an otherwise healthy host. Entomological analysis of the isolated organisms
      revealed additional information of interest.

PMID- 18713588
TI  - Primary giant cell tumor of soft tissue in the finger.
AB  - Primary giant cell tumor of soft tissue (GCTST) arising in a finger is a rare
      event. We report a case of a 54-year-old man with a primary finger giant cell
      tumor that appeared histologically identical to giant cell tumor of bone. The
      patient presented with a cystic mass of the finger. The magnetic resonance
      imaging showed no relation between the nodule and bone, tendons or synovial
      tissues. The distinction of this entity from other more common primary finger
      tumors with giant cell morphology is emphasized.

PMID- 18713589
TI  - Skin metastasis of head and neck carcinoma predictive for dismal outcome.
AB  - A 64-year-old female with locally advanced oropharyngeal carcinoma presented with
      an innocuous appearing macule on the abdomen. The lesion rapidly enlarged over 2
      weeks into an inflammatory 5 cm fleshy nodule that was diagnosed as squamous cell
      carcinoma (SCC) and was found to overexpress epidermal growth factor receptor
      (EGFR). A fatal outcome occurred 3 months after the initial diagnosis of cancer,
      in spite of chemotherapy and treatment with EGFR inhibitors (cetuximab).
      Cutaneous metastases occur in 10 percent of squamous cell carcinomas of the head
      and neck. Contiguous cutaneous metastases in the head and neck areas are by far
      the most common. Conversely, isolated infradiaphragmatic cutaneous metastases are
      exceedingly rare and are associated with an aggressive clinical course. In a
      patient with cancer, the possibility of distant skin metastasis should be
      considered whenever new cutaneous nodules appear.

PMID- 18713590
TI  - Frostbite following use of a commercially available cryotherapy device for the
      removal of viral warts.
AB  - Warts are a common skin complaint in childhood. We describe 3 unusual cases in
      which inadvertent tissue injury was caused during the treatment of viral warts by
      a commercially available cryotherapy device. In each case there was a failure to
      follow the instructions provided correctly. If such devices are to remain
      available for public use we feel changes should be implemented to reduce the risk
      of such injuries occurring again in the future. Alternatively, cryotherapy as a
      treatment modality should remain in the realm of the trained health care
      professional.

PMID- 18713591
TI  - Necrolytic acral erythema: a case not associated with hepatitis C infection.

PMID- 18713593
TI  - Linear atrophoderma of Moulin localized to the neck.
AB  - Linear atrophoderma of Moulin (LAM) is a rare and distinct skin condition
      characterized by unilateral, hyperpigmented and atrophic band-like skin lesions
      following the lines of Blaschko. Usually the disease begins in childhood or
      adolescence on the trunk or limbs, with no preceding inflammation or subsequent
      sclerodermatous changes. Approximately 25 cases have been reported in the English
      language literature. We describe a case of LAM occurring in a 9-year-old Peruvian
      boy with exclusive involvement of the neck. To our knowledge, this is the first
      report of LAM with this unusual localization.

PMID- 18713592
TI  - Paraneoplastic pemphigus associated with non-Hodgkin lymphoma.
AB  - We report a case of a 55-year-old man who, after a 6-month history of enlargement
      of cervical lymph nodes, presented with multiple painful ulcerations of the oral
      mucosa and lips and multiple skin erosions on the trunk, back, extremities, and
      genitals. A lymph node biopsy was performed and revealed diffuse peripheral B
      cell non-Hodgkin lymphoma. Skin biopsy revealed an acantholytic blister in the
      epidermis. Direct immunofluorescence showed IgG deposition in the intercellular
      spaces of the epidermis and linear C3 deposition in the basement-membrane zone.
      The indirect immunofluorescence test on rat urinary bladder epithelium was
      positive with a 1:320 titre. Paraneoplastic pemphigus was diagnosed based on
      these findings; treatment was started with cyclophosphamide, doxorubicin,
      vincristin and prednisone. The patient's response to treatment was poor and he
      developed several complications and died 2 months after diagnosis.

PMID- 18713594
TI  - Angiosarcoma of the scalp mimicking a sebaceous cyst.
AB  - A 58-year-old Caucasian woman presented with a cystic lump behind the right ear
      that was clinically diagnosed as an infected sebaceous cyst. The lesion was
      treated with incision and drainage followed by antibiotics for 3 months. Because
      there was no resolution, a biopsy was performed that revealed a high grade
      angiosarcoma. She expired 2 months later. Cutaneous angiosarcoma is an extremely
      aggressive tumor. Therefore early diagnosis and management is crucial in
      providing better patient care.

PMID- 18713595
TI  - Erythematous nodule of the eyelid.
AB  - A 68-year-old woman had a 15-day history of a well-circumscribed, erythematous
      nodule of the left eyebrow/eyelid area. After excision a primary cutaneous large
      B-cell lymphoma was diagnosed. The tumor was excised with clear margins and the
      patient has shown no recurrence over two years.

PMID- 18713596
TI  - Supernumerary nipples in association with Hailey-Hailey disease in a Tunisian
      family.
AB  - Supernumerary nipples (SNs) or polythelia are developmental abnormalities of
      breast tissue. They are located along the embryonic mammary lines. Polythelia
      usually occurs as a sporadic abnormality, although familial aggregation has been
      occasionally reported. Hailey-Hailey disease is a rare autosomal genodermatosis
      characterized by disturbed keratinocyte adhesion. These cutaneous disorders have
      been described in correlation with many other abnormalities. We report here the
      association of Hailey-Hailey disease and supernumerary nipples in a Northern
      Tunisian family. To our knowledge, this is the first report of such a clinical
      association.

PMID- 18713597
TI  - ONTODerm--a domain ontology for dermatology.
AB  - A specialty specific ontology for dermatology can be a very useful tool for
      conveying an accurate meaning to collaborative guideline applications and
      software systems. This paper describes the basics of ontology and the need for
      ontology in dermatology. We also propose the basic structure for one such
      ontology called ONTODerm. ONTODerm is grounded on DOLCE Lite foundational
      ontology and its purpose is to address the unique needs of dermatology as a
      medical specialty. It is represented in Web Ontology Language (OWL) using the
      Protege OWL Plugin. ONTODerm is available for download and collaborative
      development under GPL license.

PMID- 18713598
TI  - The origin of Adam.

PMID- 18713599
TI  - Unknown: lower extremity papules associated with easy bruising.

PMID- 18713600
TI  - Possible implantation carcinoma of the scalp following craniotomy for metastatic
      renal cell carcinoma.
AB  - We report a case of a 50-year-old man who developed a possible implantation
      carcinoma of the scalp within the craniotomy scar 19 months after a metastatic
      renal cell tumor nodule was removed from the brain. The English literature on the
      implantation carcinoma is briefly reviewed.

PMID- 18713601
TI  - Fatal outcome due to bacterial superinfection of eczema herpeticum in a patient
      with mycosis fungoides.
AB  - Kaposi varicelliform eruption or eczema herpeticum is well known to be associated
      with several chronic dermatoses, including atopic dermatitis, foliaceus
      pemphigus, seborrheic dermatitis, Darier disease, and congenital ichthyosiform
      erythroderma. Although less frequently, it has also been described in cases of
      mycosis fungoides and Sezary syndrome. We would like to report an extremely rare
      case of a woman with a T-cell cutaneous lymphoma who developed disseminated
      cutaneous herpes simplex with S. aureus sepsis and a fatal outcome.

PMID- 18713602
TI  - Erythema nodosum--an association with rabies vaccination.
AB  - A number of vaccines have been reported as causal factors in erythema nodosum. We
      report a case of erythema nodosum associated with a dog bite followed by
      vaccination for rabies. To the best of our knowledge, this is the first report of
      erythema nodosum associated with the newer generation cell culture rabies
      vaccines.

PMID- 18713603
TI  - What is the news? A difference between men and women.
AB  - It is a common observation that women and men react differently to stress and
      illness. We questioned 63 consecutive patients with pityriasis rosea and found
      that the women were overwhelmingly more likely than men to ask to hear unpleasant
      information before positive information.

PMID- 18713604
TI  - Hyperkeratotic Bowen disease--a case report.
AB  - A 70-year-old woman of Indian descent, with Fitzpatrick type IV skin type,
      presented with a 1-year history of a hyperkeratotic facial plaque. She also
      exhibited numerous signs of chronic sun damage. Hyperkeratotic squamous cell
      carcinoma in-situ was diagnosed after skin biopsy. It is important to remember
      that darkly pigmented patients do develop skin cancers.

PMID- 18713605
TI  - Unilateral mycosis fungoides.
AB  - We present an unusual case of unilateral mycosis fungoides (MF) in a 38-year-old
      woman. This woman presented to us because of multiple, localized, pruritic
      confluent plaques that appeared on the right-side of her chest and back 8 years
      ago. Skin biopsies showed characteristic findings of mycosis fungoides (e.g.,
      Pautrier microabscesses, follicular epitheliotropism, wiry bundles of collagen,
      etc.). T-cell receptor gene rearrangement analysis in the lesional skin
      demonstrated rearrangement of the gamma chain. PUVA therapy improved her skin
      lesions and pruritus, but these plaques progressed again after discontinuation of
      treatment. We conclude that MF can be localized and unilateral. Thus, a high
      index of suspicion is necessary for diagnosis of this potentially lethal disease.

PMID- 18713616
TI  - Hemoglobin plus myoglobin concentrations and near infrared light pathlength in
      phantom and pig hearts determined by diffuse reflectance spectroscopy.
AB  - To noninvasively determine absolute concentrations of hemoglobin (Hb) plus
      myoglobin (Mb) in cardiac tissue by means of regular near infrared (NIR) light
      diffuse reflectance measurements, a first derivative approach was applied. The
      method was developed to separately calculate oxygenated and deoxygenated [Hb+Mb]
      as well as an effective pathlength, which NIR light passes through in the tissue
      between optodes. Applying a cotton wool-based phantom, which mimics muscle
      tissue, it was shown that the intensity of the pseudo-optical density first
      derivative depends linearly on both oxygenated and deoxygenated Hb concentration,
      thereby validating the Lambert-Beer law in the range of 0 to 0.25 mM tetrameric
      Hb. A high correlation (R=0.995) was found between concentrations of Hb loaded
      onto the phantom and those determined spectrophotometrically, thereby verifying
      the first derivative method validity. The efficiency of the method was tested
      using in vivo pig hearts prior to and after ischemia initiated experimentally by
      left anterior descending artery branches occlusion. The results showed that the
      total [Hb+Mb] was 0.9-1.2 mM heme, the average tissue oxygen saturation was
      approximately 70% (which reduced to nearly 0% after occlusion), and the NIR (700
      965 nm) light pathlength was 2.3 mm (differential pathlength factor [DPF]=2.7
      2.8) in a living heart tissue.

PMID- 18713617
TI  - Removal of detergents from protein digests for mass spectrometry analysis.
AB  - Detergents are commonly used for the extraction of hydrophobic proteins and must
      be removed for sensitive detection of peptides by mass spectrometry. We
      demonstrate that ethyl acetate is able to extract octylglycoside from a protease
      digest without loss of peptides or interference with the peptide mass spectral
      profile. Ethyl acetate extraction was also found to reduce interference by sodium
      dodecyl sulfate, Nonidet P-40, or Triton X-100 in the mass spectrometry analysis.

PMID- 18713618
TI  - Acetyl-L-carnitine suppresses apoptosis of thioredoxin 2-deficient DT40 cells.
AB  - To elucidate the mechanism by which L-carnitine and related metabolites inhibited
      mitochondria-dependent apoptosis, we used conditional TRX2-knockout DT40 cells
      (TRX2(-/-)) and compared the properties of signaling pathways leading to
      apoptosis in the wild and TRX2(-/-) cells. Caspase-3 and 9, but not caspase-8,
      were strongly activated in TRX2(-/-) cells but not in wild cells. TRX2(-/-) cells
      generated large amounts of reactive oxygen species that markedly decreased
      cellular glutathione levels both in cytosol and mitochondria. We found that the
      critical thiol groups of adenine nucleotide translocator (ANT) were oxidized more
      easily in TRX2(-/-) cells than in wild cells and that the reduced form, but not
      oxidized form, of ANT selectively bound to TRX2. Cytochrome c and SOD1 were
      released from mitochondria more easily in TRX2(-/-) cells than in wild cells. All
      these phenomena observed with TRX2(-/-) cells were effectively inhibited by
      acetyl-L-carntine but not L-carnitine. Thus, acetyl-L-carnitine effectively
      suppressed the oxidative stress in and around mitochondria thereby preventing
      mitochondrial signaling pathway leading to apoptosis.

PMID- 18713619
TI  - LDL protein nitration: implication for LDL protein unfolding.
AB  - Oxidatively- or enzymatically-modified low-density lipoprotein (LDL) is
      intimately involved in the initiation and progression of atherosclerosis. The in
      vivo modified LDL is electro-negative (LDL(-)) and consists of peroxidized lipid
      and unfolded apoB-100 protein. This study was aimed at establishing specific
      protein modifications and conformational changes in LDL(-) assessed by liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) and circular dichroism
      analyses, respectively. The functional significance of these chemical
      modifications and structural changes were validated with binding and uptake
      experiments to- and by bovine aortic endothelial cells (BAEC). The plasma LDL(-)
      fraction showed increased nitrotyrosine and lipid peroxide content as well as a
      greater cysteine oxidation as compared with native- and total-LDL. LC/MS/MS
      analyses of LDL(-) revealed specific modifications in the apoB-100 moiety,
      largely involving nitration of tyrosines in the alpha-helical structures and
      beta(2) sheet as well as cysteine oxidation to cysteic acid in beta(1) sheet.
      Circular dichroism analyses showed that the alpha-helical content of LDL(-) was
      substantially lower ( approximately 25%) than that of native LDL ( approximately
      90%); conversely, LDL(-) showed greater content of beta-sheet and random coil
      structure, in agreement with unfolding of the protein. These results were
      mimicked by treatment of LDL subfractions with peroxynitrite (ONOO(-)) or SIN-1:
      similar amino acid modifications as well as conformational changes (loss of alpha
      helical structure and gain in beta-sheet structure) were observed. Both LDL(-)
      and ONOO(-)-treated LDL showed a statistically significant increase in binding
      and uptake to- and by BAEC compared to native LDL. We further found that most
      binding and uptake in control-LDL was through LDL-R with minimal oxLDL-R
      dependent uptake. ONOO(-)-treated LDL was significantly bound and endocytosed by
      LOX-1, CD36, and SR-A with minimal contribution from LDL-R. It is suggested that
      lipid peroxidation and protein nitration may account for the mechanisms leading
      to apoB-100 protein unfolding and consequential increase in modified LDL binding
      and uptake to and by endothelial cells that is dependent on oxLDL scavenger
      receptors.

PMID- 18713620
TI  - Down-regulation of Sprouty2 via p38 MAPK plays a key role in the induction of
      cellular apoptosis by tumor necrosis factor-alpha.
AB  - Mammalian Sprouty2 (Spry2) is a key regulator of the receptor tyrosine kinase/ERK
      signaling pathway and involved in many biological processes, including cell
      growth, migration, and tumor suppression. Here, we demonstrated that the
      intracellular protein level of Spry2 was significantly down-regulated by tumor
      necrosis factor-alpha (TNF-alpha) in both murine Swiss 3T3 fibroblasts and MLE15
      lung epithelial cells. Although TNF-alpha activates multiple signaling cascades,
      only the inhibitor of p38 MAPK pathway blocked TNF-alpha-induced Spry2 down
      regulation. Moreover, since both the mRNA level and protein half-life of Spry2
      were unaltered by TNF-alpha treatment, this indicated the possible involvement of
      a translational mechanism in mediating the inhibitory effect of TNF-alpha.
      Importantly, rescue of the TNF-alpha-induced down-regulation of Spry2 by gene
      overexpression led to reverse of the apoptotic effect of TNF-alpha in Swiss 3T3
      cells. To our knowledge, this study is the first that reported the association of
      Spry2 with TNF-alpha signaling pathway.

PMID- 18713621
TI  - Simplified purification procedure of laminin-332 and laminin-511 from human cell
      lines.
AB  - Laminins are glycoproteins expressed in the basement membrane of multiple
      epithelial tissues. Previously described purification procedures for the human
      laminin variants laminin-5 (LN-332) and laminin-10 (LN-511) use tissue as
      starting material and have multiple steps. We demonstrate a two-step laminin
      immunoaffinity purification method to produce consistent quantities of intact and
      biologically active LN-332 and LN-511 from human keratinocyte (HaCaT) and human
      lung carcinoma (A549) cell lines, respectively. The purification of LN-332 and LN
      551 was demonstrated by PAGE analysis, silver staining and Western blot analysis.
      The purification procedure includes instruction on removing a cell adhesion
      contaminant known as galectin-3 binding protein from purified LN-511. The
      biological activity of purified laminin was tested in a standard cell adhesion
      assay and compared to commercially available LN-111. This rapid and reproducible
      purification method will contribute to understanding the role of LN-332 and LN
      511 in cell behavior, signaling, and gene expression.

PMID- 18713622
TI  - Syntaxin 1A is required for normal in utero development.
AB  - We have generated a syntaxin 1A knockout mouse by deletion of exons 3 through 6
      and a concomitant insertion of a stop codon in exon 2. Heterozygous knockout
      animals were viable with no apparent phenotype. In contrast, the vast majority of
      homozygous animals died in utero, with embryos examined at day E15 showing a
      drastic reduction in body size and development when compared to WT and
      heterozygous littermates. Surprisingly, out of a total of 204 offspring from
      heterozygous breeding pairs only four homozygous animals were born alive and
      viable. These animals exhibited reduced body weight, but showed only mild
      behavioral deficiencies. Taken together, our data indicate that syntaxin 1A is an
      important regulator of normal in utero development, but may not be essential for
      normal brain function later in life.

PMID- 18713623
TI  - Role of nitric oxide and carbon monoxide in N(omega)-Nitro-L-arginine methyl
      ester-resistant acetylcholine-induced relaxation in chicken carotid artery.
AB  - The current study examined the hypothesis that acetylcholine-induced N(omega)
      Nitro-L-arginine methyl ester (L-NAME)-resistant endothelium-dependent
      relaxations in the chicken carotid artery are mediated by nitric oxide and carbon
      monoxide. Acetylcholine (1 nM-3 microM) caused a concentration-dependent
      relaxation (pD(2) 6.81+/-0.05, R(max) 115+/-3%) of the artery segments
      precontracted with phenylephrine (3 microM). L-NAME (1 mM) decreased the
      sensitivity (pD(2) 6.44+/-0.06), but not the efficacy (R(max) 108+/-3%) of
      acetylcholine. It also partially decreased the acetylcholine (3 microM)
      stimulated nitrite release. While treatment with N(omega)-Nitro-L-arginine (l
      NNA; 1 mM) plus L-NAME (1 mM) decreased the acetylcholine-stimulated nitrite
      release to the basal level, it moderately inhibited (R(max) 77+/-3%) the maximal
      relaxation elicited with the muscarinic agonist. 2-Phenyl-4,4,5,5
      tetramethylimidazoline-1-oxyl 3-oxide (PTIO; 100 microM) a specific scavenger of
      nitric oxide (NO) plus the two NOS inhibitors further decreased the acetylcholine
      evoked relaxation (R(max) 34+/-2%). Although soluble guanylyl cyclase (sGC)
      inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microM) markedly
      inhibited the acetylcholine-stimulated increase in tissue cGMP to less than the
      basal levels, it only decreased the sensitivity, but not the efficacy of the
      agonist either in the presence or absence of L-NAME (1 mM). Zinc Protoporphyrin
      IX (ZnPP; 10 microM), a hemeoxygenase (HO) inhibitor, partially inhibited (R(max)
      72+/-3%) the L-NAME-resistant acetylcholine-induced relaxations. A combined
      treatment of the arterial rings with L-NAME, l-NNA, PTIO and ZnPP nearly
      abolished (R(max) 7+/-0.9%) the vasodilator responses to acetylcholine.
      Endothelium removal abolished the relaxation response to acetylcholine. In
      conclusion, it is suggested that the acetylcholine-induced L-NAME-resistant
      relaxation is primarily, mediated by NO with a small but significant contribution
      from endothelium-derived carbon monoxide in the chicken carotid artery.

PMID- 18713624
TI  - S-adenosyl-L-methionine improves impaired hippocampal long-term potentiation and
      water maze performance induced by developmental lead exposure in rats.
AB  - Lead (Pb(2+)) exposure in children can induce long-lasting deficits in cognitive
      function and has been modeled in experimental animals. Based on previous studies
      which demonstrated that S-adenosyl-l-methionine (SAM) is beneficial in the
      treatment of lead intoxication, here, we asked the question if SAM treatment
      could rescue the impaired cognition and synaptic plasticity induced by lead. Rats
      drank 1500 ppm lead acetate (PbAc) solution or distilled water throughout
      gestation and lactation. After weaning at postnatal day 22, one half of the
      control and lead-exposed male offspring were intraperitoneally injected 20 mg
      SAM/kg daily over a period of 20-22 days. Electrophysiological and Morris water
      maze test were performed at 44-54 days of age. The result showed that the
      impaired learning ability induced by lead could be improved significantly by SAM.
      Furthermore, our results revealed that long-term potentiation (LTP) of excitatory
      postsynaptic potential and population spike impairments induced by lead were also
      ameliorated by SAM treatment.

PMID- 18713625
TI  - Emodin increases Ca(2+) influx through L-type Ca(2+) channel in guinea pig
      gallbladder smooth muscle.
AB  - Emodin is known to be used in the treatment of cholesterol stones and
      cholecystitis. This study sought to investigate the effects of emodin on the
      contraction of gallbladder smooth muscle (GBSM), intracellular Ca(2+)
      concentration and L-type calcium current in GBSM cells. Gallbladder muscle strips
      were obtained from adult guinea pigs and the resting tension was recorded.
      Gallbladder smooth muscle cells were isolated by enzymatic digestion. Cells were
      loaded with fluo-3/AM and [Ca(2+)](i) was determined by a laser confocal
      microscope. Calcium current was recorded by the whole-cell patch clamp method.
      Emodin increased the resting tension of GBSM strips in a dose-dependent manner.
      Emodin elevated [Ca(2+)](i) in GBSM cells, and this effect was attenuated by
      pretreatment with nifedipine. In addition, Emodin increased L-type calcium
      current at concentrations of 1 to 30 microM (at +10 mV, 10 microM, 45.1+/-5.2%
      compared to control, EC(50) =3.11 microM). In the presence of protein kinase C
      (PKC) inhibitor, Staurosporine, emodin did not significantly affect the calcium
      current. However, phorbol 12, 13-dibutyrate mimicked emodin in enhancement of the
      calcium current. These results suggest that emodin promotes gallbladder
      contraction by increasing Ca(2+) influx through L-type calcium channel via PKC
      pathway.

PMID- 18713626
TI  - Anisakis simplex s.l.: Larvicidal activity of various monoterpenic derivatives of
      natural origin against L3 larvae in vitro and in vivo.
AB  - This paper describes the activity against Anisakis simplex s.l. L(3) larvae of
      six monoterpenic derivatives obtained from different essential oils, (alpha
      pinene, beta-pinene, ocimene, myrcene, geranyl acetate, and cineole). In in vitro
      assays, alpha-pinene, ocimene and cineole showed high activity at a concentration
      of 125 microg/mL (48h) but only alpha-pinene and ocimene were active at 62.5
      microg/mL. In in vivo assays, L(3) larvae and study compounds were simultaneously
      administered per os to Wistar rats. The most active compound was alpha-pinene,
      finding lesions in only 20% of treated rats versus 98% of controls. Further in
      vivo studies are required to investigate whether addition of these compounds to
      food could have a prophylactic effect, reducing the pathogenicity of A. simplex
      s.l. L(3) in humans, and to explore any possible synergy among compounds.

PMID- 18713627
TI  - Focal activities and re-entrant propagations as mechanisms of gastric
      tachyarrhythmias.
AB  - BACKGROUND & AIMS: Gastric arrhythmias occur in humans and experimental animals
      either spontaneously or induced by drugs or diseases. However, there is no
      information regarding the origin or the propagation patterns of the slow waves
      that underlie such arrhythmias. METHODS: To elucidate this, simultaneous
      recordings were made on the antrum and the distal corpus during tachygastrias in
      open abdominal anesthetized dogs using a 240 extracellular electrode assembly.
      After the recordings, the signals were analyzed, and the origin and path of slow
      wave propagations were reconstructed. RESULTS: Several types of arrhythmias could
      be distinguished, including (1) premature slow waves (25% of the arrhythmias),
      (2) single aberrant slow waves (4%), (3) bursts (18%), (4) regular tachygastria
      (11%), and (5) irregular tachygastria (10%). During regular tachygastria, rapid,
      regular slow waves emerged from the distal antrum or the greater curvature,
      whereas, during irregular tachygastria, numerous variations occurred in the
      direction of propagation, conduction blocks, focal activity, and re-entry. In 12
      cases, the arrhythmia was initiated in the recorded area. In each case, after a
      normal propagating slow wave, a local premature slow wave occurred in the antrum.
      These premature slow waves propagated in various directions, often describing a
      single or a double loop that re-entered several times, thereby initiating
      additional slow waves. CONCLUSIONS: Gastric arrhythmias resemble those in the
      heart and share many common features such as focal origin, re-entry, circular
      propagation, conduction blocks, and fibrillation-like behavior.

PMID- 18713628
TI  - Endocrine effects of growth hormone overexpression in transgenic coho salmon.
AB  - Non-transgenic (wild-type) coho salmon (Oncorhynchus kisutch), growth hormone
      (GH) transgenic salmon (with highly elevated growth rates), and GH transgenic
      salmon pair fed a non-transgenic ration level (and thus growing at the non
      transgenic rate) were examined for plasma hormone concentrations, and liver,
      muscle, hypothalamus, telencephalon, and pituitary mRNA levels. GH transgenic
      salmon exhibited increased plasma GH levels, and enhanced liver, muscle and
      hypothalamic GH mRNA levels. Insulin-like growth factor-I (IGF-I) in plasma, and
      growth hormone receptor (GHR) and IGF-I mRNA levels in liver and muscle, were
      higher in fully fed transgenic than non-transgenic fish. GHR mRNA levels in
      transgenic fish were unaffected by ration-restriction, whereas plasma GH was
      increased and plasma IGF-I and liver IGF-I mRNA were decreased to wild-type
      levels. These data reveal that strong nutritional modulation of IGF-I production
      remains even in the presence of constitutive ectopic GH expression in these
      transgenic fish. Liver GHR membrane protein levels were not different from
      controls, whereas, in muscle, GHR levels were elevated approximately 5-fold in
      transgenic fish. Paracrine stimulation of IGF-I by ectopic GH production in non
      pituitary tissues is suggested by increased basal cartilage sulphation observed
      in the transgenic salmon. Levels of mRNA for growth hormone-releasing hormone
      (GHRH) and cholecystokinin (CCK) did not differ between groups. Despite its role
      in appetite stimulation, neuropeptide Y (NPY) mRNA was not found to be elevated
      in transgenic groups.

PMID- 18713629
TI  - Changes in the levels of serotonin and dopamine in the central nervous system and
      ovary, and their possible roles in the ovarian development in the giant
      freshwater prawn, Macrobrachium rosenbergii.
AB  - Serotonin or 5-hydroxytryptamine (5-HT) and dopamine (DA) are the two key
      neurotransmitters that control gonadal development in decapod crustaceans. This
      study investigated changes in the levels of 5-HT and DA in the CNS and ovary
      during different phases of the ovarian cycle of the freshwater prawn,
      Macrobrachium rosenbergii. The levels of 5-HT and DA were quantified by using
      High Performance Liquid Chromatography with electrochemical detection (HPLC-ECD).
      Moreover, changes of vitellogenin (Vg) concentrations in the hemolymph after
      treatment with 5-HT and DA (at doses of 2.5 x 10(-6) and 2.5 x 10(-7)mol per
      prawn) were also examined. 5-HT exhibited a gradual increase in concentration in
      the brain and thoracic ganglia from ovarian stage I (0.12+/-0.01 nmol/mg, 0.22+/
      0.01 nmol/mg, respectively) to reach a maximum (0.66+/-0.03 nmol/mg, 1.48+/-0.03
      nmol/mg, respectively) at ovarian stage IV. In contrast, DA in the brain and
      thoracic ganglia showed the highest concentrations at ovarian stage II (0.20+/
      0.01 nmol/mg, 1.27+/-0.06 nmol/mg, respectively) and then decreased to the lowest
      concentrations (0.06+/-0.01 nmol/mg, 0.28+/-0.04 nmol/mg, respectively) at
      ovarian stage IV. The ovarian concentration of 5-HT was 0.53+/-0.11 nmol/mg at
      ovarian stage I and gradually increased to 1.63+/-0.16 nmol/mg at ovarian stage
      IV. In contrast, the concentration of DA was highest at ovarian stage I (29.05+/
      1.31 nmol/mg), and lowest at the ovarian stage IV (11.43+/-0.74 nmol/mg).
      Injecting 5-HT into prawns significantly increased Vg concentration in the
      hemolymph at ovarian stage IV compared to control groups, and injecting DA into
      prawns had the opposite effect. The inverse relationship between 5-HT and DA
      levels in neural ganglia and ovaries, and their opposing effects on hemolymph Vg
      levels suggest that these two transmitters play opposite regulatory roles in
      controlling ovarian maturation and oocyte development in this species.

PMID- 18713630
TI  - Application of sensitive enzymeimmunoassay for determination of testosterone in
      blood plasma of yaks (Poephagus grunniens L.).
AB  - As an alternative to radioimmunoassays, a simple, highly sensitive and quick
      enzymeimmunoassay (EIA) for determination of testosterone in blood plasma of yaks
      on microtitreplates using second antibody coating technique and testosterone
      horseradish peroxidase as a label has been developed for the first time. The
      wells of the microtitreplate were coated with affinity-purified goat
      immunoglobulin (antirabbit IgG) that binds the hormone specific antibody. The EIA
      was carried out directly in 20 mICROl of plasma after 1:10 dilution with assay
      buffer. The testosterone standard curve ranged from 0.2 to 200 pg/well. The
      sensitivity of the assay was 0.20 pg/well. Testosterone standard curve in buffer
      showed parallelism with serially diluted yak plasma containing high endogenous
      testosterone. Intra- and inter-assay coefficients of variation (CV) determined
      using pooled plasma was found 5.24 and 8.54%, respectively. Recovery of known
      concentrations of added testosterone in charcoal stripped plasma was linear
      (r=0.98). For biological validation of testosterone enzymeimmunoassay, the blood
      samples were collected from yak cows at -2h before and thereafter at 2h interval
      until 24h. after gonadotropin releasing hormone (GnRH) administration. There was
      a rapid increase (p<0.01) of luteinizing hormone (LH) and testosterone 2 and 6h
      after GnRH administration. Plasma testosterone concentration in normal adult yak
      bulls was found to be 0.52+/-0.09 ng/ml. In conclusion, the EIA developed in this
      study is simple, highly sensitive, valid and sufficiently reliable method for
      estimation of testosterone directly in yak plasma.

PMID- 18713631
TI  - Transcription elements and functional expression of proopiomelanocortin genes in
      the pituitary gland of the barfin flounder.
AB  - Proopiomelanocortin (POMC) is the precursor of adrenocorticotropin, melanocyte
      stimulating hormone, and endorphin. Barfin flounder Verasper moseri possesses
      three POMC mRNAs. In this study, we determined the amino acid sequences of POMC
      A, POMC-B, and POMC-C in this fish and investigated the effects of black or white
      background on the expression of these genes. The three POMC genes (POMCs) were
      composed of three exons and two introns, wherein all the hormonal segments were
      encoded on the third exon, a pattern similar to that in other vertebrates. Intron
      B of POMC-A and POMC-B contained microsatellites of CA repeats, indicating that
      these two genes diverged from a common immediate ancestor by a recent duplication
      event. The 5'-flanking regions of the POMC-A (-1051 to -1), POMC-B (-1465 to -1),
      and POMC-C (-870 to -1) genes contained TATA boxes, Tpit, cyclic AMP response
      element-like elements, E boxes, and other elements. POMC-B and POMC-C also
      contained CCAAT boxes. The expression of the three POMCs seems to be regulated by
      synergistic interactions among a variety of transcription factors. The transfer
      of barfin flounder between tanks with different colors showed that in response to
      a black or white background, the expression of these POMCs did not always show
      similar profiles both in the neurointermediate lobe and pars distalis of the
      pituitaries. Since these POMCs are expressed in a single cell, the non
      synchronous expression of these genes suggests that different sets of
      transcription factors are associated with the transcription of each gene.

PMID- 18713632
TI  - Molecular characterization and expression of three GnRH forms mRNA during gonad
      sex-change process, and effect of GnRHa on GTH subunits mRNA in the protandrous
      black porgy (Acanthopagrus schlegeli).
AB  - Gonadotropin-releasing hormone (GnRH) plays a pivotal role in control of
      reproduction and gonadal maturation in teleost fish. To investigate the action
      GnRH in black porgy (Acanthopagrus schlegeli), we examined the mRNA expression of
      GTH subunits (GTHalpha, FSHbeta, and LHbeta) in the pituitary as well as plasma
      estradiol-17beta (E(2)) level following treatment with a GnRH analog (GnRHa) in
      immature fish. The expression levels of GTH subunits mRNA and plasma E(2) level
      were increased after GnRHa injection. We were also able to identify three GnRH
      forms: salmon GnRH (sGnRH), seabream GnRH (sbGnRH) and chicken GnRH-II (cGnRH-II)
      by cDNA cloning in the ovary of the black porgy. Black porgy gonadal development
      is divided into seven stages, involving sex change from male to female (immature
      testis, mature testis, testicular portion of mostly testis, ovarian portion of
      mostly testis, testicular portion of mostly ovary, ovarian portion of mostly
      ovary, and mature ovary). In the present study, we investigated the expression
      pattern of three GnRH molecular forms in the black porgy gonads at different
      stages of gonadal development by quantitative polymerase chain reaction (QPCR).
      The mRNA expressions of sGnRH, sbGnRH and cGnRH-II were found to be higher in
      mature testis and ovary, compared to gonads at different stages of maturity. The
      findings support the hypothesis that the three forms of GnRH play important roles
      in the regulation of hypothalamic-pituitary-gonadal axis, and are likely involved
      also in gonadal development and sex change in black porgy.

PMID- 18713633
TI  - Environmental and hormonal correlates of immune activity in a cooperatively
      breeding tropical bird.
AB  - Because climatic patterns in temperate regions are generally predictable, species
      can allocate resources adaptively among competing physiological processes before
      environmental conditions change. In the semi-arid tropics where environments are
      seasonal, but highly unpredictable, allocation decisions may be more sensitive to
      short-term fluctuations in conditions. We asked (i) whether investments in immune
      function were affected by inter-annual variation in rainfall and (ii) whether
      corticosterone and prolactin, two hormones that modulate immune activity in other
      vertebrates, predict environmentally induced alterations in immune activity in
      cooperatively breeding superb starlings (Lamprotornis superbus). Superb starlings
      inhabit African savannas characterized by high among-year variation in rainfall,
      which influences their breeding life histories and hormone levels. We quantified
      bactericidal capacity of plasma, or bacterial killing, and prolactin and
      corticosterone concentrations in blood samples collected over a four year period
      during the dry season prior to breeding, as this is the period when reproductive
      roles are determined in this species and when rainfall is most variable. We found
      that bacterial killing was weakest in the driest year of the study, and we
      detected a positive relationship between bacterial killing and prolactin, but not
      a negative relationship with corticosterone. Together these results suggest that
      prolactin may mediate rainfall-induced changes in immune activity in superb
      starlings. This study is the first to examine relationships between prolactin and
      an index of constitutive, innate immunity in birds, and suggests that even
      species inhabiting unpredictable environments adjust their physiological
      priorities to environmental conditions, perhaps via prolactin.

PMID- 18713634
TI  - Impacts of frequent, acute pulses of corticosterone on condition and behavior of
      Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii).
AB  - Little is known about how frequent, acute stressors affect wild animals. We
      present two experiments conducted on captive, Gambel's white-crowned sparrow
      (Zonotrichia leucophrys gambelii) that explore how frequent, acute doses of
      corticosterone (CORT) affect condition and behavior. CORT was administered either
      once or three times a day to birds in pre-breeding, early-breeding, or late
      breeding life-history stages. Two additional groups were included to control for
      the CORT delivery vehicle, DMSO, and the treatment process. Our results indicate
      that CORT treatment decreases condition, but that its effects are dependent on
      frequency and life stage. Specifically, CORT-treated birds delayed the onset of
      molt and had reduced body mass, flight muscle, and food consumption. CORT
      treatment did not affect fat stores, bile retention in the gallbladder, or the
      expression of migratory restlessness behavior. These results increase our
      understanding of the effects of frequent, acute stressors and the development of
      chronic stress states.

PMID- 18713635
TI  - Molecular cloning and differential expression pattern of two structural variants
      of the crustacean hyperglycemic hormone family from the mud crab Scylla olivacea.
AB  - Two full-length cDNA sequences encoding a crustacean hyperglycemic hormone (CHH)
      precursor were cloned from tissues of the mud crab Scylla olivacea. Sco-CHH (S.
      olivacea CHH) was cloned from eyestalk ganglia, whereas Sco-CHH-L (S. olivacea
      CHH-like peptide) was cloned from extra-eyestalk tissues (pericardial organ and
      thoracic ganglia). Each conceptually translated precursor is expected to be
      processed into a signal peptide, a CHH precursor-related peptide (CPRP), and a
      mature CHH or CHH-like peptide. The two precursors are identical in amino acid
      sequence through the 40th residue of the mature peptide, but different from each
      other substantially in the C-terminus. Both CHH variants contain the six highly
      conserved cysteine residues characteristic of the CHH family peptides, and share
      higher sequence identities with other brachyuran CHH sequences than with those of
      other taxonomic groups. As determined by reverse transcription-polymerase chain
      reaction (RT-PCR), the transcripts of Sco-CHH and Sco-CHH-L were present in
      eyestalk ganglia and several extra-eyestalk tissues (the thoracic ganglia,
      pericardial organ, brain, circumesophageal connectives, and gut). Sco-CHH was the
      predominant form in eyestalk ganglia, while Sco-CHH-L was the predominant form in
      several extra-eyestalk tissues. Neither transcript was expressed in the muscle,
      hepatopancreas, ovary, testis, heart, or gill. Antisera were raised against
      synthetic peptides corresponding to a stretch of sequence-specific to the C
      terminus of Sco-CHH or Sco-CHH-L. Western blot analyses of tissues expressing Sco
      CHH and Sco-CHH-L detected a Sco-CHH immunoreactive protein in the sinus gland,
      and a Sco-CHH-L immunoreactive protein in the pericardial organ.
      Immunohistochemical analyses of the eyestalk ganglia localized both Sco-CHH and
      Sco-CHH-L immunoreactivity to the sinus gland, and only Sco-CHH immunoreactivity
      to the X-organ somata; analyses of the pericardial organs also localized both Sco
      CHH and Sco-CHH-L immunoreactivity to the anterior and posterior bars, as well as
      to longitudinal trunks joining the two bars. The combined data provided
      supporting evidence that Sco-CHH and Sco-CHH-L are co-localized in the same
      tissue.

PMID- 18713636
TI  - Host associations and evolutionary relationships of avian blood parasites from
      West Africa.
AB  - The host specificity of blood parasites recovered from a survey of 527 birds in
      Cameroon and Gabon was examined at several levels within an evolutionary
      framework. Unique mitochondrial lineages of Haemoproteus were recovered from an
      average of 1.3 host species (maximum=3) and 1.2 host families (maximum=3) while
      lineages of Plasmodium were recovered from an average of 2.5 species (maximum=27)
      and 1.6 families (maximum=9). Averaged within genera, lineages of both Plasmodium
      and Haemoproteus were constrained in their host distribution relative to random
      expectations. However, while several individual lineages within both genera
      exhibited significant host constraint, host breadth varied widely among related
      lineages, particularly within the genus Plasmodium. Several lineages of
      Plasmodium exhibited extreme generalist host-parasitism strategies while other
      lineages appeared to have been constrained to certain host families over recent
      evolutionary history. Sequence data from two nuclear genes recovered from a
      limited sample of Plasmodium parasites indicated that, at the resolution of this
      study, inferences regarding host breadth were unlikely to be grossly affected by
      the use of parasite mitochondrial lineages as a proxy for biological species. The
      use of divergent host-parasitism strategies among closely related parasite
      lineages suggests that host range is a relatively labile character. Since host
      specificity may also influence parasite virulence, these results argue for
      considering the impact of haematozoa on avian hosts on a lineage-specific basis.

PMID- 18713637
TI  - Characterization of a novel Obg-like ATPase in the protozoan Trypanosoma cruzi.
AB  - We characterized a gene encoding an YchF-related protein, TcYchF, potentially
      associated with the protein translation machinery of Trypanosoma cruzi. YchF
      belongs to the translation factor-related (TRAFAC) class of P-loop NTPases. The
      coding region of the gene is 1185bp long and encodes a 44.3kDa protein. BlastX
      searches showed TcYchF to be very similar (45-86%) to putative GTP-binding
      proteins from eukaryotes, including some species of trypanosomatids (Leishmania
      major and Trypanosoma brucei). A lower but significant level of similarity (38
      43%) was also found between the predicted sequences of TcYchF and bacterial
      YyaF/YchF GTPases of the Spo0B-associated GTP-binding protein (Obg) family. Some
      of the most important features of the G domain of this family of GTPases are
      conserved in TcYchF. However, we found that TcYchF preferentially hydrolyzed ATP
      rather than GTP. The function of YyaF/YchF is unknown, but other members of the
      Obg family are known to be associated with ribosomal subunits. Immunoblots of the
      polysome fraction from sucrose gradients showed that TcYchF was associated with
      ribosomal subunits and polysomes. Immunoprecipitation assays showed that TcYchF
      was also associated with the proteasome of T. cruzi. Furthermore, inactivation of
      the T. brucei homolog of TcYchF by RNA interference inhibited the growth of
      procyclic forms of the parasite. These data suggest that this protein plays an
      important role in the translation machinery of trypanosomes.

PMID- 18713638
TI  - Identification of DNA-reactive B cells in patients with systemic lupus
      erythematosus.
AB  - Autoreactive B cells play a central role in systemic lupus erythematosus (SLE).
      Characterization of DNA-reactive B cells in the blood of lupus patients has been
      limited by the low frequency of the population. Using a tetrameric configuration
      of a peptide mimetope of DNA, we identified peptide-reactive B cells in
      peripheral blood. Antibodies derived from these B cells bound to peptide and were
      largely cross-reactive to dsDNA. This methodology enables us to track the
      development of autoreactive B cells, which recognize peptide and dsDNA, in
      individual patients with SLE and permits the isolation of autoreactive B cells
      for further characterization.

PMID- 18713639
TI  - High-yield purification of fetal tau preserving its structure and phosphorylation
      pattern.
AB  - The fetal type of tau phosphorylation always re-appears during pathogenesis of
      Alzheimer's disease and related tauopathies. The major obstacle in the study of
      the fetal tau phosphorylation has been the lack of a simple and reproducible
      purification method yielding fetal tau with high purity and unmodified
      phosphorylation pattern. We have developed a two-step, highly efficient
      purification procedure of perchloric acid-extracted fetal tau by immunoaffinity
      chromatography and trichloroacetic acid (TCA) precipitation. The method yielded
      tau with more than 90% purity. Most importantly, purified fetal tau exhibited
      unmodified phosphorylation pattern as confirmed by phosphorylation-dependent
      antibodies. In summary, this purification process preserves and protects unstable
      phosphoresidues from dephosphorylation and allows their detailed molecular
      analysis especially in the pathogenesis of Alzheimer's disease and related
      tauopathies.

PMID- 18713640
TI  - Vagal stimulation suppresses ischemia-induced myocardial interstitial myoglobin
      release.
AB  - AIMS: To evaluate vagal stimulation-mediated myocardial protection against
      ischemia and reperfusion in in vivo ischemic myocardium. MAIN METHODS: We
      measured myocardial interstitial myoglobin levels in the ischemic region using a
      cardiac microdialysis technique in anesthetized and vagotomized cats. We occluded
      the left anterior descending coronary artery (LAD) for 60 min and reperfused it
      for 60 min (VX group, n = 6). The effects of bilateral vagal stimulation (10 V, 5
      Hz, 1-ms pulse duration), initiated immediately after LAD occlusion, were
      examined (VS group, n = 6). To examine the involvement of phosphatidylinositol 3
      kinase (PI3K), vagal stimulation was performed after pretreatment with a PI3K
      inhibitor wortmannin (0.6 mg/kg, i.v.) (VS-W group, n = 6). To examine the
      contribution of bradycardia, vagal stimulation was performed with fixed-rate
      ventricular pacing (VS-P group, n = 6). KEY FINDINGS: The average myoglobin level
      during the ischemic period was 1170+/-141 in VX (in ng/ml, mean+/-SE), which was
      significantly attenuated in VS (466+/-87, P<0.05) and VS-W (613+/-124, P<0.05)
      but not in VS-P (953+/-203). Reperfusion increased the myoglobin level to 2500+/
      544 in VX, whereas it was suppressed in VS (824+/-213, P<0.05) and VS-W (948+/
      315, P<0.05) but not in VS-P (1710+/-253). SIGNIFICANCE: Vagal stimulation,
      initiated immediately after LAD occlusion, attenuated the myocardial injury.
      Moreover, bradycardia, independent of PI3K pathway, plays a significant role in
      vagally induced cardioprotection during acute myocardial ischemia.

PMID- 18713641
TI  - Long-term alterations in vulnerability to addiction to drugs of abuse and in
      brain gene expression after early life ethanol exposure.
AB  - Exposure to ethanol early in life can have long-lasting implications on brain
      function and drug of abuse response later in life. The present study investigated
      in rats, the long-term consequences of pre- and postnatal (early life) ethanol
      exposure on drug consumption/reward and the molecular targets potentially
      associated with these behavioral alterations. Since a relationship has been
      demonstrated between heightened drugs intake and susceptibility to drugs-induced
      locomotor activity/sensitization, anxiolysis, we tested these behavioral
      responses, depending on the drug, in control and early life ethanol-exposed
      animals. Our results show that progeny exposed to early life ethanol displayed
      increased consumption of ethanol solutions and increased sensitivity to cocaine
      rewarding effects assessed in the conditioned place preference test. Offspring
      exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and
      the increased sensitivity could, at least in part, explain the alteration in the
      consumption of ethanol for its anxiolytic effects. In addition, the sensitivity
      to hypothermic effects of ethanol and ethanol metabolism were not altered by
      early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to
      amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and,
      could partly explain, an increase in the rewarding properties of
      psychostimulants. Gene expression analysis revealed that expression of a large
      number of genes was altered in brain regions involved in the reinforcing effects
      of drugs of abuse. Dopaminergic receptors and transporter binding sites were also
      down-regulated in the striatum of ethanol-exposed offspring. Such long-term
      neurochemical alterations in transmitter systems and in the behavioral responses
      to ethanol and other drugs of abuse may confer an increased liability for
      addiction in exposed offspring.

PMID- 18713642
TI  - Dynamic interaction between "Go" and "Stop" signals in the saccadic eye movement
      system: New evidence against the functional independence of the underlying neural
      mechanisms.
AB  - We investigated human oculomotor behaviour in a Go-NoGo saccadic task in which
      the saccadic response to a peripheral visual target was to be inhibited in a
      minority of trials (NoGo trials). Different from classical experimental paradigms
      on the inhibitory control of intended actions, in our task the inhibitory cue was
      identical to the saccadic target (used in Go trials) in timing, location and
      shape-the only difference being its colour. By analysing the latency and the
      metrics of saccades erroneously executed after a NoGo instruction (NoGo-escapes),
      we observed a characteristic pattern of performance: first, we observed a
      decrease in the amplitude of NoGo-escapes with increasing latency; second, we
      revealed a consistent population of long-latency small saccades opposite in
      direction to the NoGo cue; finally, we found a strong side-specific inhibitory
      effect in terms of saccadic reaction times, on trials immediately following a
      NoGo trial. In addition, we manipulated the readiness to initiate a saccade
      towards the visual target, by introducing a probability bias in the random
      sequence of target locations. We found that the capacity to inhibit the impending
      saccade was improved for the most likely target location, i.e. the condition
      corresponding to the increased readiness for movement execution. Overall, our
      results challenge the notion of a central inhibitory mechanism independent from
      movement preparation. More precisely, they indicate that the two mechanisms
      (action preparation and action inhibition) interact dynamically, possibly sharing
      spatially-specific mechanisms, and are similarly affected by particular
      contextual manipulations.

PMID- 18713643
TI  - Viral delivery of heme oxygenase-1 attenuates photoreceptor apoptosis in an
      experimental model of retinal detachment.
AB  - This study was designed to evaluate the efficacy of subretinal injection of
      recombinant adeno-associated virus vector expressing heme oxygenase-1 (rAAV-HO-1)
      in attenuating photoreceptor apoptosis induced by experimental retinal detachment
      (RD) in Sprague-Dawley rats. Our results disclosed that subretinal rAAV-HO-1
      delivery achieved localized high HO-1 gene expression in retinal outer nuclear
      layer (ONL) compared with rAAV-lacZ-injected eyes and eyes with RD left untreated
      both at 2 (p=0.003) and 28 (p=0.007) days of RD. The ONL thickness (p=0.018) and
      mean photoreceptor nuclei count (p=0.009) in eyes receiving rAAV-HO-1 injection
      was significantly higher than in rAAV-lacZ-injected or eyes with RD left
      untreated at 28 days of RD. There were fewer apoptotic photoreceptor nuclei at 2
      (p=0.008) and 5 (p=0.018) days of RD and less activated caspase-3 expression
      (p=0.008) at 2 days of RD in rAAV-HO-1 treated eyes than in control eyes. These
      data supported that gene transfer approach might attenuate photoreceptor
      apoptosis caused by RD with a resultant better ONL preservation.

PMID- 18713645
TI  - Thrombus causes fluctuations in arterial drug delivery from intravascular stents.
AB  - Arterial drug concentrations determine local toxicity. As such the emergent
      safety concerns surrounding drug-eluting stents mandate an investigation of the
      factors contributing to fluctuations in arterial drug uptake. Drug-eluting stents
      were implanted into porcine coronary arteries, arterial drug uptake was followed
      and modeled using 2-dimensional computational drug transport. Arterial drug
      uptake in vivo occurred faster than predicted by free drug diffusion, thus an
      alternate, mechanism for rapid transport has been proposed involving carrier
      mediated transport. Though there was minimal variation in vivo in release
      kinetics from stent to stent, arterial drug deposition varied by up to 114% two
      weeks after stent implantation. The extent of adherent mural thrombus also
      fluctuated by 113% within 3 days after implantation. The computational drug
      transport model predicted that focal and diffuse thrombi elevate arterial drug
      deposition in proportion to the thrombus size by reducing drug washout
      subsequently increasing local drug availability. Fluctuations in arterial drug
      uptake are commonly reported. We now explain that variable peristrut thrombus can
      explain such observations even in the face of a narrow range of drug release from
      the stent. The mural thrombus effects on arterial drug deposition may be
      circumvented by forcing slow, rate limiting arterial transport that cannot be
      further hindered by mural thrombus.

PMID- 18713644
TI  - Autonomic activation associated with ethanol self-administration in adult female
      P rats.
AB  - The present study examined changes in heart rate (HR) prior to and during limited
      access ethanol drinking in adult female P rats. P rats were implanted with radio
      telemetric transmitters to measure HR. Daily testing involved a 90-min pre-test
      period (water only available) and a subsequent 90-min test period [either water
      (W) or ethanol available]. After a week of habituation, one ethanol group had
      access to ethanol for 7 weeks (CE), and another ethanol group had access for 4
      weeks, was deprived for 2 weeks and then had access for a final week (DEP).
      Analyses of HR revealed that CE and DEP rats had significantly higher HR than W
      rats during test periods that ethanol was present and that DEP rats displayed
      higher HR during the early test period of the ethanol deprivation interval, as
      well. These data indicate that ethanol drinking induces HR activation in adult
      female P rats, and that this activation can be conditioned to the test cage
      environment, paralleling reports on contextual conditioning and cue-reactivity in
      alcoholics exposed to alcohol-associated stimuli. Therefore, this behavioral test
      may prove advantageous in screening pharmacotherapies for reducing craving and
      relapse, which are associated with cue-reactivity in abstinent alcoholics.

PMID- 18713646
TI  - Noise exposure-induced enhancement of auditory cortex response and changes in
      gene expression.
AB  - Noise exposure is one of the most common causes of hearing loss. There is growing
      evidence suggesting that noise-induced peripheral hearing loss can also induce
      functional changes in the central auditory system. However, the physiological and
      biological changes in the central auditory system induced by noise exposure are
      poorly understood. To address these issues, neurophysiological recordings were
      made from the auditory cortex (AC) of awake rats using chronically implanted
      electrodes before and after acoustic overstimulation. In addition, focused gene
      microarrays and quantitative real-time polymerase chain reaction were used to
      identify changes in gene expression in the AC. Monaural noise exposure (120 dB
      sound pressure level, 1 h) significantly elevated hearing threshold on the
      exposed ear and induced a transient enhancement on the AC response amplitude 4 h
      after the noise exposure recorded from the unexposed ear. This increase of the
      cortical neural response amplitude was associated with an upregulation of genes
      encoding heat shock protein (HSP) 27 kDa and 70 kDa after several hours of the
      noise exposure. These results suggest that noise exposure can induce a fast
      physiological change in the AC which may be related to the changes of HSP
      expressions.

PMID- 18713647
TI  - Inhibitory effect of the Jendrassik maneuver on the stretch reflex.
AB  - The Jendrassik maneuver (JM) is a method for enhancing sluggish tendon-tap jerks
      at medical examination. It is the thesis of this paper that JM effects should not
      be limited to the monosynaptic reflex pathway but extend to the entire response
      elicited in the stretched muscle. This consists of a short-latency response (SLR)
      corresponding to the mono- and oligosynaptic reflex and a medium-latency response
      (MLR) relayed by group-II spindle afferent fibers and likely made of a segmental
      burst and a transcortical loop. Soleus (Sol) SLR and MLR were evoked by toe-up
      and tibialis anterior (TA) MLR by toe-down platform rotation in 15 standing
      subjects and recorded by surface electromyogram (EMG). For each stimulus type, up
      to 20 perturbations were elicited during i) quiet stance (Control) and while ii)
      performing JM, iii) leaning forward (FW), iv) holding onto a stable frame
      (Holding). For each subject, stimulus type and condition, rectified EMG traces
      were averaged. Based on the comparison of the population grand averages,
      selective effects of JM on the responses were identified. Appropriate time
      windows were set for measuring the area of SLR and of the early and late burst of
      MLR (MLR1 and MLR2). Significant changes in response size, but not latency, were
      induced by all conditioning procedures. During toe-up, JM slightly increased Sol
      SLR; FW increased both Sol background activity and SLR; MLR1 was not affected by
      JM, but increased by FW; MLR2 was strongly diminished by JM and increased by FW.
      During toe-down, JM did not affect TA MLR1, but strongly diminished MLR2. Under
      Holding condition, Sol SLR to toe-up was unaffected, but both MLR1 and MLR2 to
      toe-up and toe-down were diminished, in both Sol and TA. JM selectively decreases
      the response component (MLR2) starting about 100 ms from onset of the stretch, in
      both extensor and flexor muscles. Latency and quality of the JM effect on MLR2
      indicate that JM operates by gating a long-loop, possibly transcortical pathway.
      This new information suggests that lesions of cortical areas or descending
      pathways can exert enhancing effects on muscle tone by removing an inhibitory
      action on the late component of the stretch reflex.

PMID- 18713648
TI  - Chronic lentiviral expression of inwardly rectifying K+ channels (Kir2.1) reduces
      neuronal activity and downregulates voltage-gated potassium currents in
      hippocampus.
AB  - Strongly inwardly rectifying K+ (Kir2) channels are endogenously expressed in rat
      brains and have recently been used as a tool to reduce the neuronal activity. But
      little is known about the role of Kir2 channels and the chronic effect of the
      reduced activity on the intrinsic excitability of neurons. Here we constructed a
      lentiviral vector that coexpressed Kir2.1 and GFP (LvKir2.1) and infected the
      vector to the hippocampal slice cultures. The LvKir2.1-infected CA1 neurons
      showed clear inwardly rectifying K+ currents for more than 15 days. The resting
      membrane potential was more negative by approximately 10 mV than those uninfected
      or infected with the lentiviral vector expressing GFP alone. The infection of
      LvKir2.1 reduced the voltage change in response to current injections and the
      amplitude of mEPSPs with a shunting effect. The LvKir2.1 infection significantly
      reduced the firings evoked by depolarizing currents in the CA1 neurons. The
      reduction of the firing was attributed to the hyperpolarized potential rather
      than to the shunting effect. These reductions were limited to modest current
      injections, suggesting that the overexpressed Kir2.1 plays the role of a noise
      filter. Moreover, the chronic overexpression of Kir2.1 downregulated the
      expression of the delayed rectifier potassium current in a homeostatic manner,
      indicating a usefulness of this viral vector to study the activity-dependent
      neuronal development.

PMID- 18713649
TI  - JNK regulates cell migration through promotion of tyrosine phosphorylation of
      paxillin.
AB  - The adaptor protein paxillin plays an important role in cell migration. Although
      the c-Jun amino-terminal kinase (JNK) phosphorylation of paxillin on Ser 178 has
      been found to be critical for cell migration, the precise mechanism by which JNK
      regulates cell migration is still not very clear. Here, the migration of human
      corneal epithelial (HCE) cells was used to determine which signaling pathways are
      involved in EGF-induced paxillin phosphorylation. Paxillin was phosphorylated on
      Tyr 31 and Tyr 118 after induction of migration by EGF in HCE cells. Specific
      inhibition of JNK activation by inhibitor SP600125 or overexpression of a
      dominant-negative JNK mutant not only blocked EGF-induced cell migration, but
      also eliminated tyrosine phosphorylation of paxillin on Tyr 31 and Tyr 118. HCE
      cells overexpressing paxillin-S178A mutant also exhibited lower mobility, and
      reduced phosphorylation of Tyr 31 and Tyr 118. However, paxillin-S178A-inhibited
      cell migration can be rescued by overexpression of paxillin-Y31E/Y118E mutant.
      Importantly, inhibition of JNK by SP600125 or overexpression of paxillin-S178A
      mutant prevented the association of FAK with paxillin. Taken together, these
      results suggest that phosphorylation of paxillin on Ser 178 by JNK is required
      for the association of paxillin with FAK, and subsequent tyrosine phosphorylation
      of paxillin.

PMID- 18713651
TI  - Phylogenetic relationships and biogeography of the Japanese clawed salamander,
      Onychodactylus japonicus (Amphibia: Caudata: Hynobiidae), and its congener
      inferred from the mitochondrial cytochrome b gene.
AB  - Using the mitochondrial cytochrome b gene, we investigated phylogenetic
      relationships between and within the Japanese clawed salamander, Onychodactylus
      japonicus, and its close continental relative O. fischeri. Monophyly of O.
      japonicus was well supported, and O. japonicus was clearly distinguished from O.
      fischeri. However, O. fischeri comprises genetically distinct populations from
      Russia, NE China, and Korea that do not form a monophyletic group. Within O.
      japonicus, four major clades were clearly recognized: Clade I from northern
      Tohoku district, Clade II from southern Tohoku district and the Tsukuba
      Mountains, Clade III from southwestern Honshu, and Clade IV from Kinki and
      Chugoku districts in Honshu and from Shikoku. Although genetic distances among
      these clades were large (5.5-9.6%), relationships among the clades were
      unresolved. All clades except Clade I contained two or three distinct subclades.
      In several localities in Kinki and Chugoku, Clades III and IV were sympatric. The
      estimated divergence times and available geohistorical data suggest that O.
      japonicus began to differentiate in the Upper Late Miocene and that the pattern
      of genetic differentiation of this species has been affected strongly by climate
      changes and geohistorical events such as volcanic activity and mountain
      formation. Our results suggest that both O. fischeri and O. japonicus comprise
      multiple cryptic species.

PMID- 18713650
TI  - Enhanced protein expression in the baculovirus/insect cell system using
      engineered SUMO fusions.
AB  - Recombinant protein expression in insect cells varies greatly from protein to
      protein. A fusion tag that is not only a tool for detection and purification, but
      also enhances expression and/or solubility would greatly facilitate both
      structure/function studies and therapeutic protein production. We have shown that
      fusion of SUMO (small ubiquitin-related modifier) to several test proteins leads
      to enhanced expression levels in Escherichia coli. In eukaryotic expression
      systems, however, the SUMO tag could be cleaved by endogenous desumoylase. In
      order to adapt SUMO-fusion technology to these systems, we have developed an
      alternative SUMO-derived tag, designated SUMOstar, which is not processed by
      native SUMO proteases. In the present study, we tested the SUMOstar tag in a
      baculovirus/insect cell system with several proteins, i.e. mouse UBP43, human
      tryptase beta II, USP4, USP15, and GFP. Our results demonstrate that fusion to
      SUMOstar enhanced protein expression levels at least 4-fold compared to either
      the native or His(6)-tagged proteins. We isolated active SUMOstar tagged UBP43,
      USP4, USP15, and GFP. Tryptase was active following cleavage with a SUMOstar
      specific protease. The SUMOstar system will make significant impact in difficult
      to-express proteins and especially to those proteins that require the native N
      terminal residue for function.

PMID- 18713652
TI  - In vitro comparison of the prebiotic effects of two inulin-type fructans.
AB  - Faecal cultures were used to compare the prebiotic effects of a new fructan
      containing high solubility inulin (HSI) and of a well-established prebiotic
      containing oligofructose (OF) with a negative control (CT). Changes in the
      intestinal microbiota, pH, ammonia, volatile organic acids and lactic acid were
      monitored during incubation. Molecular techniques for microbial enumeration
      indicated that both HSI and OF led to a significant increase in bifidobacteria
      (P< or =0.05) and lactobacilli (P< or =0.05) compared to the control. Significant
      changes in the pH and levels of ammonia with both inulin-type fructans were
      observed, as well as higher levels of acetic, lactic and formic acids (P< or
      =0.05). The fermentative metabolism appeared to be faster on OF than on HSI. Both
      OF and HSI showed clear prebiotic effects, but had differences in fermentation
      kinetics because of to the different degree of polymerization (DP). This study
      provides proof for the prebiotic effectiveness of HSI, and shows that inulin-type
      fructans with higher DP might have a prolonged bifidogenic effect, thus could
      extend the saccharolytic metabolism and low pH to the distal parts of the colon.

PMID- 18713653
TI  - PACAP inhibit the release and cytokine activity of HMGB1 and improve the survival
      during lethal endotoxemia.
AB  - The pathogenesis of sepsis is mediated in part by bacterial endotoxin
      (lipopolysaccharide; LPS), which stimulates macrophages/monocytes to sequentially
      release early (e.g., TNF-alpha, IL-1beta) and late [e.g., high mobility group box
      1 (HMGB1) protein] pro-inflammatory cytokines. Specifically targeting early
      mediators has not been effective clinically, in part, because peak mediator
      activity often has passed before therapy can be initiated. Recent discovery of
      HMGB1 as a late mediator of lethal sepsis has provided a new target for the
      treatment of septic shock. Here, we demonstrate that pituitary adenylate cyclase
      activating polypeptide (PACAP), an endogenous neuropeptide, significantly
      attenuated circulating HMGB1 levels and increased survival in animals with
      established endotoxemia, even if treatment began after acute cytokine response
      has occurred. In vitro, PACAP suppressed LPS-induced HMGB1 release from
      macrophages/monocytes, even when given 2-4 h after LPS stimulation. PACAP also
      suppressed HMGB1 release induced by TNF-alpha or IFN-gamma. Moreover, PACAP
      inhibits HMGB1-induced cytokine release in vitro and in vivo. These results
      indicate that PACAP inhibits the release and pro-inflammatory activity of HMGB1
      and improves survival during lethal endotoxemia, which confirms this peptide as a
      candidate for therapy of septic shock.

PMID- 18713654
TI  - The current and future state of asthma treatment. Introduction.

PMID- 18713655
TI  - ABCs of Asthma.
AB  - Asthma results from chronic airway inflammation involving a diversity of
      activated cells including mast cells, eosinophils, T-lymphocytes, neutrophils,
      macrophages, and epithelial cells. These cells release proinflammatory cytokine
      mediators that augment and regulate airway inflammation, leading to airway
      hyperresponsiveness responsible for the chronic asthma symptoms of dyspnea,
      wheezing, and chest tightness. It is hypothesized, but unproven, that
      inflammatory effects can lead to irreversible structural and functional airway
      changes. Early intervention with anti-inflammatory agents mitigates inflammatory
      changes, reverses airway obstruction, and may possibly prevent progression of
      airway remodeling. Current asthma guidelines recommend that initial management
      should be based on pretreatment assessments of asthma severity as determined by
      measures of clinical and spirometric impairment in individual patients;
      subsequent adjustments of pharmacotherapy and avoidance recommendations should be
      performed at regular follow-up visits and guided by frequent assessments of
      asthma control. Physicians and providers should continually educate asthmatic
      patients about proper use of asthma controller medications, avoidance of asthma
      triggers, and self-management of asthma exacerbations.

PMID- 18713656
TI  - Asthma management and prevention: current perspectives.
AB  - The continuing evolution of asthma treatment and prevention are reflected in
      updated guidelines from the National Asthma Education and Prevention Program and
      Global Initiative for Asthma as well as other recent publications. The 2007
      Expert Panel Report 3 guidelines designate severity and control, mediated by
      considerations of current impairment and future risk, as the primary concepts in
      assessing and monitoring asthma. Severity should ideally be determined at the
      time of diagnosis, after which control becomes the central focus of asthma
      management. In the area of treatment, inhaled corticosteroids (ICSs) remain first
      line therapy for longterm asthma management in children and adults. For patients
      whose severity of asthma requires more than low-dose ICSs, or whose asthma cannot
      be well controlled on monotherapy with low-dose ICSs, evidence supports the
      efficacy of combination therapy consisting of an ICS plus an inhaled long-acting
      beta2-agonist (LABA) or an increase to medium-dose ICSs. For children >5 years of
      age and adults not controlled on low-dose ICSs, the combination of a low-dose ICS
      plus an inhaled LABA is equivalent in terms of outcomes to the use of medium-dose
      ICS. For children <5 years of age not controlled on low-dose ICSs, increasing the
      dose of ICSs is preferred to the addition of a LABA to low-dose ICS therapy as no
      studies using combination therapy have been conducted for patients in this age
      group. With regard to asthma prevention, approaches to primary prevention (to
      avoid allergen sensitization) and secondary prevention (to avoid disease
      progression) are still very much in the developmental stage, while tertiary
      prevention (to avoid asthmatic stimuli) has been more successful particularly in
      pediatric patients. Written action plans as part of self-management processes
      appear to improve physician-patient communication and disease status tracking.
      Other considerations in successful asthma management include patient education
      and monitoring of adherence to treatment regimens.

PMID- 18713657
TI  - Asthma in infants and children.
AB  - Asthma is the most common chronic illness in childhood and represents a
      significant burden to health care and educational systems. Between one quarter
      and two thirds of childhood asthma cases persist into adulthood. Childhood asthma
      may be particularly difficult to diagnose because of the high prevalence of
      episodic wheezing and cough in childhood illnesses such as upper respiratory
      tract infections. National and worldwide guidelines for the management of asthma
      in children are continually being updated. These guidelines recommend first
      establishing a diagnosis and assessing the severity of disease, initiating
      pharmacologic therapy based on symptoms and lung function, and adjusting doses
      and agents as required based on the level of asthma control. Inhaled
      corticosteroids are the cornerstone of long-term asthma management in children of
      all ages. Recent research efforts have focused on ways to improve inhalant drug
      delivery to the lungs and minimize oral and systemic bioavailability so as to
      improve the therapeutic benefit:risk ratio.

PMID- 18713658
TI  - Advances in therapy for adult asthma.
AB  - There are >22 million Americans with asthma. Chronic asthma is a worldwide
      problem with an increasing socioeconomic burden on individuals and on society.
      Recent advances have been made in diagnostic lung imaging, defining control of
      asthma, as well as in the education of patients with asthma. Accurate diagnosis
      of the cause of chronic cough in adults and of asthma in elderly individuals will
      help affected individuals receive appropriate treatment. Inhaled corticosteroids
      are the recommended first-line therapy for persistent asthma and can help prevent
      exacerbations in patients with asthma that are not well controlled. Early
      intervention and improved management can significantly reduce the socioeconomic
      burden of asthma. Patient education is an essential part of asthma management.

PMID- 18713660
TI  - Mental rotation of mirrored letters: evidence from event-related brain
      potentials.
AB  - Event-related brain potentials (ERPs) were recorded while participants (n=13)
      were presented with mirrored and normal letters at different orientations and
      were asked to make mirror-normal letter discriminations. As it has been suggested
      that a mental rotation out of the plane might be necessary to decide on mirrored
      letters, we wanted to determine whether this rotation occurs after the plane
      rotation in mirror rotated letters. The results showed that mirrored letters in
      the upright position elicited a negative-going waveform over the right hemisphere
      in the 400-500 ms window. A similar negativity was also present in mirrored
      letters at 30 degrees, 60 degrees, and 90 degrees, but in these cases it was
      delayed. Moreover, the well-known orientation effect on the amplitude of the
      rotation-related negativity was also found, although it was more evident for
      normal than for mirrored letters. These results indicate that the processing of
      mirrored letters differs from that of normal letters, and suggest that a rotation
      out of the plane after the plane rotation may be involved in the processing of
      mirror rotated letters.

PMID- 18713659
TI  - Clinical, pathological, and molecular correlates in ferroportin disease: a study
      of two novel mutations.
AB  - BACKGROUND/AIMS: Clinico-pathological manifestations of ferroportin (Fpn) disease
      (FD) are heterogeneous, with some patients presenting with iron overload
      predominantly in macrophages ("M" phenotype), others predominantly in hepatocytes
      ("H" phenotype). This appears to reflect functional heterogeneity of Fpn mutants,
      with loss-of-function generally resulting in the M type. METHODS: Two unrelated
      probands with "non-HFE" hemochromatosis were screened for Fpn mutations. Mutants
      were functionally characterized by immunofluorescence microscopy, evaluation of
      their ability to bind hepcidin and export iron, and by expressing them in
      zebrafish. RESULTS: Two novel Fpn mutations were identified: I152F in patient-1,
      presenting with typical M phenotype; and L233P in patient-2, presenting with
      ambiguous features (massive overload in both macrophages and hepatocytes).
      Molecular studies suggested loss of function in both cases. The I152F, normally
      localized on cell membrane and internalized by hepcidin, showed a unique
      "primary" deficit of iron export capability. The L233P did not appropriately
      traffic to cell surface. Loss of function was confirmed by expressing both
      mutants in vivo in zebrafish, resulting in iron limited erythropoiesis. Clinical
      manifestations were likely enhanced in both patients by non-genetic factors (HCV,
      alcohol). CONCLUSIONS: The combination of careful review of clinico-pathological
      data with molecular studies can yield compelling explanations for phenotype
      heterogeneity in FD.

PMID- 18713661
TI  - Chestnut pellicle for the recovery of gold.
AB  - Recovery of Au(III) from hydrochloric acid medium by using crosslinked chestnut
      pellicle (CCP) gel was studied. Strong selectivity was observed for Au(III)
      showing negligible affinity for other precious metals and some base metal ions
      tested. The adsorption isotherm study exhibited the maximum loading capacity of
      the gel as high as 10.6 mol or about 2.1 kg gold per kg dry weight of gel. The
      reduction of Au(III) ion to elemental form during adsorption process is expected
      to be the reason of high selectivity and high capacity for Au(III). Kinetic
      studies at various temperatures confirm an endothermic adsorption process
      following the pseudo-first order rate law.

PMID- 18713662
TI  - Characterization of an extracellular polysaccharide produced by a Pseudomonas
      strain grown on glycerol.
AB  - A new extracellular charged polysaccharide composed mainly by galactose, with
      lower amounts of mannose, glucose and rhamnose, was produced by the cultivation
      of Pseudomonas oleovorans NRRL B-14682 using glycerol as the sole carbon source.
      Thermal and solid-state NMR analysis showed that this polymer is essentially
      amorphous, with a glass transition temperature of 155.7 degrees C. The
      exopolysaccharide aqueous solutions have viscoelastic properties similar to that
      of Guar gum, but with affinity to salts as a result of its polyelectrolyte
      character. In addition, the exopolysaccharide has demonstrated good flocculating
      and emulsifying properties and film-forming capacity. These properties make this
      polymer a good alternative to more expensive natural polysaccharides, such as
      Guar gum, in several applications in the food, pharmaceutical, cosmetic, textile,
      paper and petroleum industries.

PMID- 18713663
TI  - Enhanced enzymatic hydrolysis of sugarcane bagasse by N-methylmorpholine-N-oxide
      pretreatment.
AB  - The cellulose dissolution solvent used in Lyocell process for cellulose fiber
      preparation, N-methylmorpholine-N-oxide (NMMO) monohydrate, was demonstrated to
      be an effective agent for sugarcane bagasse pretreatment. Bagasse of 20wt% was
      readily dissolved in NMMO monohydrate at 130 degrees C within 1h. After
      dissolution, bagasse could be regenerated by rapid precipitation with water as a
      porous and amorphous mixture of its original components. The regenerated bagasse
      exhibited a significant enhancement on enzymatic hydrolysis kinetic. Not only the
      reducing sugars releasing rate but also hydrolysis yield was enhanced at least
      twofold as compared with that of untreated bagasse. The cellulose fraction of
      regenerated bagasse was nearly hydrolyzed to glucose after 72h hydrolysis with
      Cellulase AP3. The recycled NMMO demonstrated the same performance as the fresh
      one on bagasse pretreatment for hydrolysis enhancement. The regenerated bagasse
      was directly used in simultaneous saccharification and fermentation (SSF) for
      ethanol production by Zymomonas mobilis. No negative effect on ethanol
      fermentation was observed and ethanol yield approximately 0.15 g ethanol/g
      baggasse was achieved.

PMID- 18713664
TI  - Experimental study on air-stream gasification of biomass micron fuel (BMF) in a
      cyclone gasifier.
AB  - Based on biomass micron fuel (BMF) with particle size of less than 250 microm, a
      cyclone gasifier concept has been considered in our laboratory for biomass
      gasification. The concept combines and integrates partial oxidation, fast
      pyrolysis, gasification, and tar cracking, as well as a shift reaction, with the
      purpose of producing a high quality of gas. In this paper, experiments of BMF air
      stream gasification were carried out by the gasifier, with energy for BMF
      gasification produced by partial combustion of BMF within the gasifier using a
      hypostoichiometric amount of air. The effects of ER (0.22-0.37) and S/B (0.15
      0.59) and biomass particle size on the performances of BMF gasification and the
      gasification temperature were studied. Under the experimental conditions, the
      temperature, gas yields, LHV of the gas fuel, carbon conversion efficiency,
      stream decomposition and gasification efficiency varied in the range of 586-845
      degrees C, 1.42-2.21 N m(3)/kg biomass, 3806-4921 kJ/m(3), 54.44%-85.45%, 37.98%
      70.72%, and 36.35%-56.55%, respectively. The experimental results showed that the
      gasification performance was best with ER being 3.7 and S/B being 0.31 and
      smaller particle, as well as H(2)-content. And the BMF gasification by air and
      low temperature stream in the cyclone gasifier with the energy self-sufficiency
      is reliable.

PMID- 18713665
TI  - Identification of ring-fused pyrazolo pyridin-2-ones as novel poly(ADP
      ribose)polymerase-1 inhibitors.
AB  - A novel class of PARP-1 inhibitors was identified containing a non-aromatic
      heterocycle or carbocycle fused to a pyrazolo pyridin-2-one. Compounds displayed
      low nanomolar binding activity in the PARP-1 binding assay and submicromolar
      activity in a cell based chemosensitization assay.

PMID- 18713666
TI  - Synthesis and potent antileukemic activities of 10-benzyl-9(10H)-acridinones.
AB  - A novel series of 10-benzyl-9(10H)-acridinones and 1-benzyl-4-piperidones were
      synthesized and tested for their in vitro antitumor activities against CCRF-CEM
      cells. Assay-based antiproliferative activity study using CCRF-CEM cell lines
      revealed that the acridone group and the substitution pattern on the benzene unit
      had significant effect on cytotoxicity of this series of compounds, among which
      10-(3,5-dimethoxy)benzyl-9(10H)-acridinone (3b) was found to be the most active
      compound with IC(50) at about 0.7 microM. Compound 3b was also found to have
      antiproliferative activity against two other human leukemic cell lines K562 and
      HL60 using the MTT assay. The antitumor effect of 3b is believed to be due to the
      induction of apoptosis, which is further confirmed by PI (Propidium iodide)
      staining and Annexin V-FITC/PI staining assay using flow cytometry analysis.

PMID- 18713667
TI  - The tert-butoxyl radical mediated hydrogen atom transfer reactions of the
      Parkinsonian proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and
      selected tertiary amines.
AB  - Previous studies have shown that the hydrogen atom transfer (HAT) reactions of
      tert-butoxyl radical from the Parkinsonian proneurotoxin 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) occur with low selectivity at the allylic and
      non-allylic alpha-C-H positions. In this paper, we report a more comprehensive
      regiochemical study on the reactivity of the tert-butoxyl radical as well as on
      the associated primary kinetic deuterium isotope effects for the various hydrogen
      atom abstractions of MPTP. In addition, the results of a computational study to
      estimate the various C-H bond dissociation energies of MPTP are presented. The
      results of the present study show the allylic/non-allylic selectivity is
      approximately 73:21. The behavior of the tert-butoxyl radical mediated oxidation
      of MPTP contrasts with this reaction as catalyzed by monoamine oxidase B (MAO-B)
      that occurs selectively at the allylic alpha-carbon. These observations lead to
      the conclusion that the tert-butoxyl radical is not a good chemical model for the
      MAO-B-catalyzed bioactivation of MPTP.

PMID- 18713668
TI  - Modulatory effects of hypercapnia on in vitro and in vivo pulmonary endothelial
      neutrophil adhesive responses during inflammation.
AB  - Reducing tidal volume as a part of a protective ventilation strategy may result
      in hypercapnia. In this study, we focused on the influence of hypercapnia on
      endothelial-neutrophil responses in models of inflammatory-stimulated human
      pulmonary microvascular endothelial cells (HMVEC) and in an animal model of
      lipopolysaccharide (LPS)-induced acute lung injury. Neutrophil adhesion and
      adhesion molecules expression and nuclear factor-kappaB (NF-kappaB) were analyzed
      in TNF-alpha and LPS-treated HMVEC exposed to either eucapnia or hypercapnia. In
      the in vivo limb, bronchoalveolar lavage fluid cell counts and differentials,
      adhesion molecule and chemokine expression were assessed in LPS-treated rabbits
      ventilated with either low tidal volume ventilation and eucapnia or hypercapnia.
      In both the in vitro and in vivo models, hypercapnia significantly increased
      neutrophil adhesion and adhesion molecule expression compared to eucapnia.
      Activity of NF-kappaB was significantly enhanced by hypercapnia in the in vitro
      experiments. IL-8 expression was greatest both in vitro and in vivo under
      conditions of hypercapnia and concomitant inflammation. CD11a expression was
      greatest in isolated human neutrophils exposed to hypercapnia+LPS. Our results
      demonstrate that endothelial-neutrophil responses per measurement of fundamental
      molecules of adhesion are significantly increased during hypercapnia and that
      hypercapnia mimics conditions of eucapnia+inflammation.

PMID- 18713669
TI  - Co-delivery of FGF-2 and G-CSF from gelatin-based hydrogels as angiogenic therapy
      in a murine critical limb ischemic model.
AB  - Peripheral artery disease and critical limb ischemia have become prevalent health
      risks in the United States due to an increasing elderly population and the
      prevalence of obesity and diabetes mellitus. Although highly invasive
      endarterectomy is the most popular method for treatment, angiogenic therapies
      based on growth factor administration are quickly becoming a popular alternative.
      Enzymatic degradation of these factors in vivo may be avoided by their
      incorporation in a delivery vehicle where the growth factor's release rate can be
      controlled by altering the vehicle's properties (i.e. cross-linking density,
      material selection, biodegradation, etc.). Herein, we report on the
      immobilization and controlled release of human recombinant basic fibroblast
      growth factor (FGF-2) and human recombinant granulocyte colony-stimulating factor
      (G-CSF) from ionic, gelatin-based hydrogel scaffolds to re-establish perfusion
      and induce capillary outgrowth in a murine hindlimb ischemic model. In vitro
      studies showed that endothelial cell proliferation was highly depended on FGF-2,
      whereas G-CSF stimulated migration and formation of a tubular network. When FGF-2
      and G-CSF were used in combination there was an 82% increase in endothelial
      branch point formation compared to control groups. Leg reperfusion was assessed
      with laser Doppler perfusion imaging, while capillary outgrowth in the ischemic
      leg was evaluated using CD31(+) and alpha-SMA immunostaining. The co-delivery of
      G-CSF (1000 ngml(-1)) and FGF-2 (1000 ng ml(-1)) from the gelatin hydrogels
      resulted in a 3-fold increase in the perfusion levels and a 2-fold increase in
      capillary density and positive alpha-SMA vessels compared to the empty vehicle
      group. In conclusion, the co-delivery of FGF-2 and G-CSF was superior to bolus
      administration or the delivery of either factor alone in promoting reperfusion
      and mature vessel formation.

PMID- 18713670
TI  - Activation of P2Y receptors by ATP and by its analogue, ADPbetaS, triggers two
      calcium signal pathways in the longitudinal muscle of mouse distal colon.
AB  - Our previous research showed that ATP and adenosine 5'-O-2-thiodiphosphate
      (ADPbetaS) induce contractile effects in the longitudinal muscle of mouse distal
      colon via activation of P2Y receptors which are not P2Y(1) or P2Y(12) subtypes.
      This study investigated the nature of the P2Y receptor subtype(s) and the
      mechanisms leading to the intracellular calcium concentration increase necessary
      to trigger muscular contraction. Motor responses of mouse colonic longitudinal
      muscle to P2Y receptor agonists were examined in vitro as changes in isometric
      tension. ATP or ADPbetaS induced muscular contraction, which was not affected by
      P2Y(11) or P2Y(13) selective antagonists. Calcium-free solution or the calcium
      channel blocker, nifedipine, failed to modify the contractile responses to ATP or
      ADPbetaS, which were virtually abolished by depletion of calcium intracellular
      stores after repetitive addition of carbachol in calcium-free medium with
      addition of cyclopiazonic acid. Neomycin or U-73122, phospholipase C inhibitors,
      or 2-aminoethoxy-diphenylborate (2-APB), membrane-permeant IP(3) receptor
      inhibitor reduced the response to ATP, whilst ryanodine or ruthenium red,
      inhibiting calcium release from ryanodine-sensitive stores, abolished the
      response to ADPbetaS. Responses to maximally effective concentrations of ATP and
      ADPbetaS were not fully additive. Desensitisation with ADPbetaS antagonized the
      contractile effects of ATP, as desensitisation with ATP antagonized the response
      to ADPbetaS. In the longitudinal muscle of mouse distal colon, ATP and ADPbetaS
      induce muscular contraction via a P2Y receptor, coupled to differential signal
      pathways leading to intracellular calcium increase.

PMID- 18713671
TI  - Adaptive rate-distortion optimal in-loop quantization for matching pursuit.
AB  - In this paper, an adaptive in-loop quantization technique is proposed for
      quantizing inner product coefficients in matching pursuit. For each matching
      pursuit (MP) stage a different quantizer is used based on the probability
      distribution of MP coefficients. The quantizers are optimized for a given rate
      budget constraint. Additionally, our proposed adaptive quantization scheme finds
      the optimal quantizers for each stage based on the already encoded inner product
      coefficients. Experimental results show that our proposed adaptive quantization
      scheme outperforms existing quantization methods used in matching pursuit image
      coding.

PMID- 18713672
TI  - Resource allocation for downlink multiuser video transmission over wireless lossy
      networks.
AB  - Demand for multimedia services, such as video streaming over wireless networks,
      has grown dramatically in recent years. The downlink transmission of multiple
      video sequences to multiple users over a shared resource-limited wireless
      channel, however, is a daunting task. Among the many challenges in this area are
      the time-varying channel conditions, limited available resources, such as
      bandwidth and power, and the different transmission requirements of different
      video content. This work takes into account the time-varying nature of the
      wireless channels, as well as the importance of individual video packets, to
      develop a cross-layer resource allocation and packet scheduling scheme for
      multiuser video streaming over lossy wireless packet access networks. Assuming
      that accurate channel feedback is not available at the scheduler, random channel
      losses combined with complex error concealment at the receiver make it impossible
      for the scheduler to determine the actual distortion of the sequence at the
      receiver. Therefore, the objective of the optimization is to minimize the
      expected distortion of the received sequence, where the expectation is calculated
      at the scheduler with respect to the packet loss probability in the channel. The
      expected distortion is used to order the packets in the transmission queue of
      each user, and then gradients of the expected distortion are used to efficiently
      allocate resources across users. Simulations show that the proposed scheme
      performs significantly better than a conventional content-independent scheme for
      video transmission.

PMID- 18713673
TI  - Nonlinearities in stereoscopic phase-differencing.
AB  - Exploiting the quasi-linear relationship between local phase and disparity, phase
      differencing registration algorithms provide a fast, powerful means for disparity
      estimation. Unfortunately, these phase-differencing techniques suffer a
      significant impediment: phase nonlinearities. In regions of phase nonlinearity,
      the signals under consideration possess properties that invalidate the use of
      phase for disparity estimation. This paper uses the amenable properties of
      Gaussian white noise images to analytically quantify these properties. The
      improved understanding gained from this analysis enables us to better understand
      current methodologies for detecting regions of phase instability. Most
      importantly, we introduce a new, more effective means for identifying these
      regions based on the second derivative of phase.

PMID- 18713674
TI  - Incremental refinement of image salient-point detection.
AB  - Low-level image analysis systems typically detect "points of interest", i.e.,
      areas of natural images that contain corners or edges. Most of the robust and
      computationally efficient detectors proposed for this task use the
      autocorrelation matrix of the localized image derivatives. Although the
      performance of such detectors and their suitability for particular applications
      has been studied in relevant literature, their behavior under limited input
      source (image) precision or limited computational or energy resources is largely
      unknown. All existing frameworks assume that the input image is readily available
      for processing and that sufficient computational and energy resources exist for
      the completion of the result. Nevertheless, recent advances in incremental image
      sensors or compressed sensing, as well as the demand for low-complexity scene
      analysis in sensor networks now challenge these assumptions. In this paper, we
      investigate an approach to compute salient points of images incrementally, i.e.,
      the salient point detector can operate with a coarsely quantized input image
      representation and successively refine the result (the derived salient points) as
      the image precision is successively refined by the sensor. This has the advantage
      that the image sensing and the salient point detection can be terminated at any
      input image precision (e.g., bound set by the sensory equipment or by
      computation, or by the salient point accuracy required by the application) and
      the obtained salient points under this precision are readily available. We focus
      on the popular detector proposed by Harris and Stephens and demonstrate how such
      an approach can operate when the image samples are refined in a bitwise manner,
      i.e., the image bitplanes are received one-by-one from the image sensor. We
      estimate the required energy for image sensing as well as the computation
      required for the salient point detection based on stochastic source modeling. The
      computation and energy required by the proposed incremental refinement approach
      is compared against the conventional salient-point detector realization that
      operates directly on each source precision and cannot refine the result. Our
      experiments demonstrate the feasibility of incremental approaches for salient
      point detection in various classes of natural images. In addition, a first
      comparison between the results obtained by the intermediate detectors is
      presented and a novel application for adaptive low-energy image sensing based on
      points of saliency is presented.

PMID- 18713675
TI  - Wavelet feature selection for image classification.
AB  - Energy distribution over wavelet subbands is a widely used feature for wavelet
      packet based texture classification. Due to the overcomplete nature of the
      wavelet packet decomposition, feature selection is usually applied for a better
      classification accuracy and a compact feature representation. The majority of
      wavelet feature selection algorithms conduct feature selection based on the
      evaluation of each subband separately, which implicitly assumes that the wavelet
      features from different subbands are independent. In this paper, the dependence
      between features from different subbands is investigated theoretically and
      simulated for a given image model. Based on the analysis and simulation, a
      wavelet feature selection algorithm based on statistical dependence is proposed.
      This algorithm is further improved by combining the dependence between wavelet
      feature and the evaluation of individual feature component. Experimental results
      show the effectiveness of the proposed algorithms in incorporating dependence
      into wavelet feature selection.

PMID- 18713676
TI  - The Effects on Kinematics and Muscle Activity of Walking in a Robotic Gait
      Trainer During Zero-Force Control.
AB  - "Assist as needed" control algorithms promote activity of patients during robotic
      gait training. Implementing these requires a free walking mode of a device, as
      unassisted motions should not be hindered. The goal of this study was to assess
      the normality of walking in the free walking mode of the LOPES gait trainer, an 8
      degrees-of-freedom lightweight impedance controlled exoskeleton. Kinematics, gait
      parameters and muscle activity of walking in a free walking mode in the device
      were compared with those of walking freely on a treadmill. Average values and
      variability of the spatio-temporal gait variables showed no or small (relative to
      cycle-to-cycle variability) changes and the kinematics showed a significant and
      relevant decrease in knee angle range only. Muscles involved in push off showed a
      small decrease, whereas muscles involved in acceleration and deceleration of the
      swing leg showed an increase of their activity. Timing of the activity was mainly
      unaffected. Most of the observed differences could be ascribed to the inertia of
      the exoskeleton. Overall, walking with the LOPES resembled free walking, although
      this required several adaptations in muscle activity. These adaptations are such
      that we expect that Assist as Needed training can be implemented in LOPES.

PMID- 18713677
TI  - Investigating scale invariant dynamics in minimum toe clearance variability of
      the young and elderly during treadmill walking.
AB  - Current research applying variability measures of gait parameters has
      demonstrated promise for helping to solve one of the "holy grails" of geriatric
      research by defining markers that can be used to prospectively identify persons
      at risk of falling . The minimum toe clearance (MTC) event occurs during the leg
      swing phase of the gait cycle and is a task highly sensitive to the spatial and
      balance control properties of the locomotor system. The aim of this study is to
      build upon the current state of research by investigating the magnitude and
      dynamic structure from the MTC time series fluctuations due to aging and
      locomotor disorder. Thirty healthy young (HY), 27 healthy elderly (HE), and 10
      falls risk (FR) elderly individuals (who presented a prior history of trip
      related falls) participated in treadmill walking for at least 10 min at their
      preferred speed. Continuous MTC data were collected and the first 512 data points
      were analyzed. The following variability indices were quantified: 1) MTC mean and
      standard deviation (SD), 2) PoincarE plot indices of MTC variability (SD1, SD2,
      SD1/SD2), 3) a wavelet based multiscale exponent beta to describe the dynamic
      structure of MTC fluctuations, and 4) detrended fluctuation analysis exponent
      alpha to investigate the presence of long-range correlations in MTC time series
      data. Results showed that stride-to-stride MTC time series has a nonlinear
      structure in all three groups when compared against randomly shuffled surrogate
      MTC data. Test on aging effects showed the MTC central tendency was significantly
      lower (p < 0.01) and the magnitude of the MTC variability significantly higher (p
      < 0.01). This trend changed when comparing FR subjects against age-matched HE as
      both the central tendency (p < 0.01) and magnitude of the variability (p < 0.01)
      increased significantly in FR. Although the magnitude of MTC variability
      increased with age, the nonlinear indices represented by alpha, beta, and SD1/SD2
      demonstrated that the nonlinear structure of MTC does not change significantly
      due to aging (p > 0.05). There were, however, significant differences between HY
      and FR for beta (between scale 1 and 2; p < 0.01) and alpha (p < 0.05). Out of
      all the variability measures applied, beta(Wv2-4), SD1/SD2, SD2 of critical MTC
      parameter were found to be potential markers to be able to reliably identify FR
      from HE subjects. Further research is required to understand the mechanisms
      underlying the cause of MTC variability.

PMID- 18713678
TI  - Receptive field characteristics under electrotactile stimulation of the
      fingertip.
AB  - Skin on human fingertips has high concentrations of mechanoreceptors, which are
      used to provide fine resolution tactile representations of our environment. Here,
      we explore the ability to discriminate electrotactile stimulation at four sites
      on the fingertip. Electrical stimulation was delivered to arrays of electrodes
      centered on the index fingertip (volar aspect). Accuracy of discrimination was
      tested by examining electrode size, interelectrode spacing, and stimulation
      frequency as primary factors. Electrical stimulation was delivered at 2 mA with
      the pulse width modulated to be at (or above) perceptual threshold at 25 and 75
      Hz and an average pulse width of 1.03 ms (+/- 0.70 ms standard deviation).
      Discrimination of the stimulated locations under this stimulation paradigm was
      significantly above chance level in all cases. Subjects' ability to discriminate
      stimulus location was not significantly influenced by electrode size or
      stimulation frequency when considered as separate factors. However, increased
      electrode spacing significantly increased subjects' ability to discriminate the
      location of the stimulated electrode. Further analysis revealed that errors were
      only significantly reduced along the medial-lateral direction with increasing
      interelectrode spacing. These results suggest that the electrotactile stimulus
      localization on the fingertip has some directional dependency, in addition to its
      dependency on interelectrode spacing. The neural mechanisms underlying this
      phenomenon are discussed in relation to electrical stimulus transduction
      characteristics of tactile mechanoreceptors.

PMID- 18713679
TI  - Stimulation of the expiratory muscles using microstimulators.
AB  - Respiratory complications constitute a major cause of morbidity and mortality in
      patients with spinal cord injury. These complications arise in part due to the
      loss of supraspinal control over the expiratory muscles and the resultant
      difficulties in clearing airway secretions effectively. The purpose of the
      present study is to evaluate the efficacy of lower thoracic spinal nerve
      stimulation using wireless microstimulators in activating the expiratory muscles.
      Studies were performed on nine anesthetized dogs. A thoracic laminectomy was
      performed on each dog,and was followed by spinal cord transection at T2. A total
      of 16 microstimulators (supplied by the Alfred Mann Foundation, Santa Clarita,
      CA) were inserted percutaneously into the bilateral intercostal nerves
      approximately 1 to approximately 3 cm distal to the neuroforamen from T7 to L1 in
      each dog. The stimulation parameters were: frequency of 20 Hz, pulse width of 200
      micros, and stimulation burst of 2 s. The stimulation intensities were 3.78, 5.4,
      8.1, and 10.8 mA. The pressure-generating capacity of the expiratory muscles was
      evaluated by the change in airway pressure (Paw) at functional residual capacity,
      which was produced by the microstimulators during airway occlusion. As a general
      trend, the expiratory pressure generated using the microstimulators increased
      with increasing intensity and the number of spinal nerves recruited. The maximal
      expiratory pressures generated from one, two, three, four, five, six, seven, and
      eight pairs of spinal nerves were 8.4 +/- 0.8, 12.2 +/- 1.0, 14.6 +/- 1.4, 17.8
      +/- 1.8, 23.0 +/- 1.8, 27.7 +/- 2.2, 35.2 +/- 2.7, and 40.4 +/- 2.9 cmH2O,
      respectively. Bilateral stimulation of seven (from T8 to L1) and eight spinal
      nerve levels (from T7 to L1) produced the highest changes in(Paw). Stimulation of
      six or less spinal nerve levels resulted in significantly lower (Paw). We
      conclude: 1) lower thoracic spinal nerve stimulation near the neuroforamen using
      microstimulators produces significant expiratory pressure, 2) percutaneous
      placement of the microstimulators near the neuroforamen is effective in producing
      expiratory pressure, and 3) percutaneous placement of the microstimulators for
      restoring cough may potentially be used as a relatively noninvasive clinical tool
      for patients with spinal cord injury, or other neurological or respiratory
      disorders. Further studies will be needed.

PMID- 18713680
TI  - Acoustic FMRI noise: linear time-invariant system model.
AB  - Functional magnetic resonance imaging (fMRI) enables sites of brain activation to
      be localized in human subjects. For auditory system studies, however, the
      acoustic noise generated by the scanner tends to interfere with the assessments
      of this activation. Understanding and modeling fMRI acoustic noise is a useful
      step to its reduction. To study acoustic noise, the MR scanner is modeled as a
      linear electroacoustical system generating sound pressure signals proportional to
      the time derivative of the input gradient currents. The transfer function of one
      MR scanner is determined for two different input specifications: 1) by using the
      gradient waveform calculated by the scanner software and 2) by using a recording
      of the gradient current. Up to 4 kHz, the first method is shown as reliable as
      the second one, and its use is encouraged when direct measurements of gradient
      currents are not possible. Additionally, the linear order and average damping
      properties of the gradient coil system are determined by impulse response
      analysis. Since fMRI is often based on echo planar imaging (EPI) sequences, a
      useful validation of the transfer function prediction ability can be obtained by
      calculating the acoustic output for the EPI sequence. We found a predicted sound
      pressure level (SPL) for the EPI sequence of 104 dB SPL compared to a measured
      value of 102 dB SPL. As yet, the predicted EPI pressure waveform shows similarity
      as well as some differences with the directly measured EPI pressure waveform.

PMID- 18713681
TI  - Boundary element computations in the forward and inverse problems of
      electrocardiography: comparison of collocation and Galerkin weightings.
AB  - In electrocardiographic imaging, epicardial potentials are reconstructed
      computationally from electrocardiographic measurements. The reconstruction is
      typically done with the help of the boundary element method (BEM), using the
      point collocation weighting and constant or linear basis functions. In this
      paper, we evaluated the performance of constant and linear point collocation and
      Galerkin BEMs in the epicardial potential problem. The integral equations and
      discretizations were formulated in terms of the single- and double-layer
      operators. All inner element integrals were calculated analytically. The
      computational methods were validated against analytical solutions in a simplified
      geometry. On the basis of the validation, no method was optimal in all testing
      scenarios. In the forward computation of the epicardial potential, the linear
      Galerkin (LG) method produced the smallest errors. The LG method also produced
      the smallest discretization error on the epicardial surface. In the inverse
      computation of epicardial potential, the electrode-specific transfer matrix
      performed better than the full transfer matrix. The Tikhonov 2 regularization
      outperformed the Tikhonov 0. In the optimal modeling conditions, the best BEM
      technique depended on electrode positions and chosen error measure. When large
      modeling errors such as omission of the lungs were present, the choice of the
      basis and weighting functions was not significant.

PMID- 18713683
TI  - Gaussian process robust regression for noisy heart rate data.
AB  - Heart rate data collected during nonlaboratory conditions present several data
      modeling challenges. First, the noise in such data is often poorly described by a
      simple Gaussian; it has outliers and errors come in bursts. Second, in large
      scale studies the ECG waveform is usually not recorded in full, so one has to
      deal with missing information. In this paper, we propose a robust postprocessing
      model for such applications. Our model to infer the latent heart rate time series
      consists of two main components: unsupervised clustering followed by Bayesian
      regression. The clustering component uses auxiliary data to learn the structure
      of outliers and noise bursts. The subsequent Gaussian process regression model
      uses the cluster assignments as prior information and incorporates expert
      knowledge about the physiology of the heart. We apply the method to a wide range
      of heart rate data and obtain convincing predictions along with uncertainty
      estimates. In a quantitative comparison with existing postprocessing methodology,
      our model achieves a significant increase in performance.

PMID- 18713682
TI  - Modeling of prosthetic limb rotation control by sensing rotation of residual arm
      bone.
AB  - We proposed a new approach to improve the control of prosthetic arm rotation in
      amputees. Arm rotation is sensed by implanting a small permanent magnet into the
      distal end of the residual bone, which produces a magnetic field. The position of
      the bone rotation can be derived from magnetic field distribution detected with
      magnetic sensors on the arm surface, and then conveyed to the prosthesis
      controller to manipulate the rotation of the prosthesis. Proprioception remains
      intact for residual limb skeletal structures; thus, this control system should be
      natural and easy-to-use. In this study, simulations have been conducted in an
      upper arm model to assess the feasibility and performance of sensing the
      voluntary rotation of residual humerus with an implanted magnet. A sensitivity
      analysis of the magnet size and arm size was presented. The influence of relative
      position of the magnet to the magnetic sensors, orientation of the magnet
      relative to the limb axis, and displacement of the magnetic sensors on the
      magnetic field was evaluated. The performance of shielding external magnetostatic
      interference was also investigated. The simulation results suggest that the
      direction and angle of rotation of residual humerus could be obtained by decoding
      the magnetic field signals with magnetic sensors built into a prosthetic socket.
      This pilot study provides important guidelines for developing a practical
      interface between the residual bone rotation and the prosthesis for control of
      prosthetic rotation.

PMID- 18713684
TI  - Speckle noise reduction of medical ultrasound images in complex wavelet domain
      using mixture priors.
AB  - Speckle noise is an inherent nature of ultrasound images, which may have negative
      effect on image interpretation and diagnostic tasks. In this paper, we propose
      several multiscale nonlinear thresholding methods for ultrasound speckle
      suppression. The wavelet coefficients of the logarithm of image are modeled as
      the sum of a noise-free component plus an independent noise. Assuming that the
      noise-free component has some local mixture distribution (MD), and the noise is
      either Gaussian or Rayleigh, we derive the minimum mean squared error (MMSE) and
      the averaged maximum a posteriori (AMAP) estimators for noise reduction. We use
      Gaussian and Laplacian MD for each noise-free wavelet coefficient to characterize
      their heavy-tailed property. Since we estimate the parameters of the MD using the
      expectation maximization (EM) algorithm and local neighbors, the proposed MD
      incorporates some information about the intrascale dependency of the wavelet
      coefficients. To evaluate our spatially adaptive despeckling methods, we use both
      real medical ultrasound and synthetically introduced speckle images for speckle
      suppression. The simulation results show that our method outperforms several
      recently and the state-of-the-art techniques qualitatively and quantitatively.

PMID- 18713685
TI  - Robust predictive control strategy applied for propofol dosing using BIS as a
      controlled variable during anesthesia.
AB  - This paper presents the application of predictive control to drug dosing during
      anesthesia in patients undergoing surgery. The performance of a generic
      predictive control strategy in drug dosing control, with a previously reported
      anesthesia-specific control algorithm, has been evaluated. The robustness
      properties of the predictive controller are evaluated with respect to inter- and
      intrapatient variability. A single-input (propofol) single-output (bispectral
      index, BIS) model of the patient has been assumed for prediction as well as for
      simulation. A set of 12 patient models were studied and interpatient variability
      and disturbances are used to assess robustness of the controller. Furthermore,
      the controller guarantees the stability in a desired range. The applicability of
      the predictive controller in a real-life environment via simulation studies has
      been assessed.

PMID- 18713686
TI  - A study on the possible usefulness of detrended fluctuation analysis of the
      electroencephalogram background activity in Alzheimer's disease.
AB  - We studied the EEG background activity of Alzheimer's disease (AD) patients with
      detrended fluctuation analysis (DFA). DFA provides an estimation of the scaling
      information and long-range correlations in time series. We recorded the EEG in 11
      AD patients and 11 age-matched controls. Our results showed two scaling regions
      in all subjects' channels (for limited time scales from 0.01 to 0.04 s and from
      0.08 to 0.43 s, respectively), with a clear bend when their corresponding slopes
      (alpha(1) and alpha(2)) were different. No significant differences between groups
      were found with alpha(1). However, alpha(2) values were significantly lower in
      control subjects at electrodes T5, T6, and O1 (p < 0.01, Student's t-test). These
      findings suggest that the scaling behavior of the EEG is sensitive to AD.
      Although alpha(2) values allowed us to separate AD patients and controls,
      accuracies were lower than with spectral analysis. However, a forward stepwise
      linear discriminant analysis with a leave-one-out cross-validation procedure
      showed that the combined use of DFA and spectral analysis could improve the
      diagnostic accuracy of each individual technique. Thus, although spectral
      analysis outperforms DFA, the combined use of both techniques may increase the
      insight into brain dysfunction in AD.

PMID- 18713687
TI  - Decomposition of intramuscular EMG signals using a heuristic fuzzy expert system.
AB  - Although increasingly sophisticated algorithms have been proposed to decompose
      intramuscular electromyography signals into the concurrent activities of
      individual motor units (MUs), the human operator is still able to improve
      decomposition results by visual inspection. The rationale for this paper was to
      combine components from previous decomposition procedures in an expert systems
      approach utilizing fuzzy logic and attempting to replicate the thought process of
      an accomplished decomposer in order to minimize the user interaction subsequently
      needed to enhance decomposition results. The decomposition procedure is discussed
      and examples are given of the type of information it can yield. The method has
      been used to identify the discharge activities of up to 15 MUs with up to 95%
      accuracy.

PMID- 18713688
TI  - Integrated approach for fetal QRS detection.
AB  - Fetal magnetocardiography provides reliable signals of the fetal heart dynamics
      with high temporal resolution that can be used in a clinical setting. We present
      a robust Hilbert transform method for extraction of the fetal heart rate. Our
      method may be applied to signals derived from a single channel or an array of
      channels. In the case of multichannel data, the channels can be combined to
      improve signal-to-noise ratio for the extraction of fetal heart data. The method
      is inherently insensitive to fetal position or movement and, in addition, can be
      automated. We demonstrate that the determination of R-wave timing is relatively
      insensitive to waveform morphology. The method can also be applied if the data
      were preprocessed by independent component analysis (ICA). We compared the
      Hilbert method, ICA, ICA + Hilbert, and raw signals and found that the Hilbert
      method gave the best overall performance. We demonstrated that there were
      approximately 171 errors in 46,789 fetal heart beats.

PMID- 18713689
TI  - A comparison of the effects of electrode implantation and targeting on pattern
      classification accuracy for prosthesis control.
AB  - The use of surface versus intramuscular electrodes as well as the effect of
      electrode targeting on pattern-recognition-based multifunctional prosthesis
      control was explored. Surface electrodes are touted for their ability to record
      activity from relatively large portions of muscle tissue. Intramuscular
      electromyograms (EMGs) can provide focal recordings from deep muscles of the
      forearm and independent signals relatively free of crosstalk. However, little
      work has been done to compare the two. Additionally, while previous
      investigations have either targeted electrodes to specific muscles or used
      untargeted (symmetric) electrode arrays, no work has compared these approaches to
      determine if one is superior. The classification accuracies of pattern
      recognition-based classifiers utilizing surface and intramuscular as well as
      targeted and untargeted electrodes were compared across 11 subjects. A repeated
      measures analysis of variance revealed that when only EMG amplitude information
      was used from all available EMG channels, the targeted surface, targeted
      intramuscular, and untargeted surface electrodes produced similar classification
      accuracies while the untargeted intramuscular electrodes produced significantly
      lower accuracies. However, no statistical differences were observed between any
      of the electrode conditions when additional features were extracted from the EMG
      signal. It was concluded that the choice of electrode should be driven by
      clinical factors, such as signal robustness/stability, cost, etc., instead of by
      classification accuracy.

PMID- 18713690
TI  - Multilevel statistical inference from functional near-infrared spectroscopy data
      during stroop interference.
AB  - Functional near-infrared spectroscopy (fNIRS) is an emerging technique for
      monitoring the concentration changes of oxy- and deoxy-hemoglobin (oxy-Hb and
      deoxy-Hb) in the brain. An important consideration in fNIRS-based neuroimaging
      modality is to conduct group-level analysis from a set of time series measured
      from a group of subjects. We investigate the feasibility of multilevel
      statistical inference for fNIRS. As a case study, we search for hemodynamic
      activations in the prefrontal cortex during Stroop interference. Hierarchical
      general linear model (GLM) is used for making this multilevel analysis.
      Activation patterns both at the subject and group level are investigated on a
      comparative basis using various classical and Bayesian inference methods. All
      methods showed consistent left lateral prefrontal cortex activation for oxy-Hb
      during interference condition, while the effects were much less pronounced for
      deoxy-Hb. Our analysis showed that mixed effects or Bayesian models are more
      convenient for faithful analysis of fNIRS data. We arrived at two important
      conclusions. First, fNIRS has the capability to identify activations at the group
      level, and second, the mixed effects or Bayesian model is the appropriate
      mechanism to pass from subject to group-level inference.

PMID- 18713691
TI  - Removal of the eye-blink artifacts from EEGs via STF-TS modeling and robust
      minimum variance beamforming.
AB  - A novel scheme for the removal of eye-blink (EB) artifacts from
      electroencephalogram (EEG) signals based on a novel space-time-frequency (STF)
      model of EEGs and robust minimum variance beamformer (RMVB) is proposed. In this
      method, in order to remove the artifact, the RMVB is provided with a priori
      information, namely, an estimation of the steering vector corresponding to the
      point source EB artifact. The artifact-removed EEGs are subsequently
      reconstructed by deflation. The a priori knowledge, the vector corresponding to
      the spatial distribution of the EB factor, is identified using the STF model of
      EEGs, provided by the parallel factor analysis (PARAFAC) method. In order to
      reduce the computational complexity present in the estimation of the STF model
      using the three-way PARAFAC, the time domain is subdivided into a number of
      segments, and a four-way array is then set to estimate the STF-time/segment (TS)
      model of the data using the four-way PARAFAC. The correct number of the factors
      of the STF model is effectively estimated by using a novel core consistency
      diagnostic- (CORCONDIA-) based measure. Subsequently, the STF-TS model is shown
      to closely approximate the classic STF model, with significantly lower
      computational cost. The results confirm that the proposed algorithm effectively
      identifies and removes the EB artifact from raw EEG measurements.

PMID- 18713692
TI  - Source localization of event-related potentials incorporating spatial notch
      filters.
AB  - A novel algorithm for the localization of event-related potential (ERP) sources
      within the brain is proposed here. In this technique, spatial notch filters are
      developed to exploit the multichannel electroencephalogram data together with a
      model of ERP with variable parameters in order to accurately localize the
      corresponding ERP signal sources. The algorithm is robust in the presence of
      reasonably high noise. The performance of the proposed system has been compared
      to that of linear constrained minimum variance (LCMV) beamformer for different
      noise and correlation levels and its superiority has been demonstrated.

PMID- 18713693
TI  - ECG denoising and compression using a modified extended Kalman filter structure.
AB  - This paper presents efficient denoising and lossy compression schemes for
      electrocardiogram (ECG) signals based on a modified extended Kalman filter (EKF)
      structure. We have used a previously introduced two-dimensional EKF structure and
      modified its governing equations to be extended to a 17-dimensional case. The new
      EKF structure is used not only for denoising, but also for compression, since it
      provides estimation for each of the new 15 model parameters. Using these specific
      parameters, the signal is reconstructed with regard to the dynamical equations of
      the model. The performances of the proposed method are evaluated using standard
      denoising and compression efficiency measures. For denosing, the SNR improvement
      criterion is used, while for compression, we have considered the compression
      ratio (CR), the percentage area difference (PAD), and the weighted diagnostic
      distortion (WDD) measure. Several Massachusetts Institute of Technology-Beth
      Israel Deaconess Medical Center (MIT-BIH) ECG databases are used for performance
      evaluation. Simulation results illustrate that both applications can contribute
      to and enhance the clinical ECG data denoising and compression performance. For
      denoising, an average SNR improvement of 10.16 dB was achieved, which is 1.8 dB
      more than the next benchmark methods such as MABWT or EKF2. For compression, the
      algorithm was extended to include more than five Gaussian kernels. Results show a
      typical average CR of 11.37:1 with WDD << 1.73%. Consequently, the proposed
      framework is suitable for a hybrid system that integrates these algorithmic
      approaches for clean ECG data storage or transmission scenarios with high output
      SNRs, high CRs, and low distortions.

PMID- 18713694
TI  - Preliminary feasibility study of an in-line phase contrast X-ray imaging
      prototype.
AB  - In this study, a series of imaging experiments on biological specimens, including
      human breast core biopsies, lumpectomy, and chicken tissues, as well as standard
      phantoms, were performed in an effort to investigate the feasibility of an in
      line phase contrast X-ray imaging prototype. The prototype system employed in the
      study consists of a microfocus X-ray source with tungsten target and a digital
      flat panel detector, and it can be operated in both conventional attenuation
      based imaging mode and in-line phase contrast imaging mode. Biological specimens
      were imaged in the conventional mode and phase contrast mode with the same source
      to-image-detector distance (SID), and phase contrast images exhibited both
      improved image quality compared with conventional images, and the overshooting
      patterns along the boundaries in the specimens, which revealed the occurrence of
      the edge enhancement effect provided by the phase contrast technique. In
      addition, the performance of the phase contrast mode and conventional mode was
      compared based on the American College of Radiology (ACR) phantom imaging and
      contrast detail mammography (CDMAM) phantom-based contrast detail analysis with
      two experimental settings: one with the same SID and the other with the same
      object entrance exposure. In both pairs of comparison under our experimental
      conditions, the phase contrast imaging mode exhibited improved image quality as
      compared to the conventional mode, which further supported the feasibility of the
      prototype.

PMID- 18713695
TI  - Collagenase-aided intracortical microelectrode array insertion: effects on
      insertion force and recording performance.
AB  - Intracortical microelectrodes puncture the intact pia mater membrane during
      insertion, a process that can cause brain dimpling and trauma. To ensure that the
      device is able to withstand forces during implantation without buckling, the
      selection of acceptable implant materials and geometries is limited to rigid
      designs with large cross-sectional areas. Such designs likely increase insertion
      trauma and potentially exacerbate the chronic tissue response. In this paper, a
      technique that may relax the mechanical requirements of implanted microelectrodes
      through enzymatic (collagenase mediated) manipulation of the pia mater is
      quantified experimentally. Measurements of the insertion force profiles were
      obtained with a load cell during computer controlled (10 microm/s) insertion of
      microwire arrays into the cortex of rats. It was observed that collagenase
      application reduced the peak insertion force experienced by the microwire arrays
      by almost 40% on average (4.04 +/-2.03 mN versus 2.36 +/-1.17 mN; control versus
      treated sites). Peak insertion force magnitudes were highly dependent on implant
      location with anterior sites registering lower peaks than more posterior sites.
      Chronic neural recording performance (up to one month) did not appear to be
      adversely affected by the collagenase treatment, suggesting the overall safety of
      the technique. Our data suggest that controlled application of collagenase is a
      useful method in enabling implantation of thinner microelectrodes, potentially
      facilitating reduced insertion trauma and lower immune response. Furthermore, due
      to dependence of insertion force on anatomical location, the intended target
      region should be considered in implant design.

PMID- 18713696
TI  - Irreversible electroporation attenuates neointimal formation after angioplasty.
AB  - Restenosis following coronary angioplasty represents a major clinical problem.
      Irreversible electroporation (IRE) is a nonthermal, nonpharmacological cell
      ablation method. IRE utilizes a sequence of electrical pulses that produce
      permanent damage to tissue within a few seconds. METHODS AND RESULTS: The left
      carotid arteries of eight rats underwent in vivo intimal damage using two Fogarty
      angioplasty catheters. The procedure was immediately followed by IRE ablation in
      four rats, while the remaining four were used as the control group. The IRE
      ablation was performed using a sequence of ten dc pulses of 3800 V/cm, 100 micros
      each, at a frequency of ten pulses per second, applied across the blood vessel
      between two parallel electrodes. The electrical conductance of the treated tissue
      was measured during the electroporation to provide real-time feedback of the
      process. Left carotid arteries were excised and fixated after a 28-day follow-up
      period. Neointimal formation was evaluated histologically. The use of IRE was
      successful in three out of four animals in a way that is consistent with the
      measurements of blood vessel electrical properties. The integrity of the
      endothelial layer was recovered in the IRE-treated animals, compared with
      control. Successful IRE reduced neointima to media ratio (0.57 +/-0.4 versus 1.88
      +/-1.0, P = 0.02). CONCLUSIONS: We report for the first time the in vivo results
      of attenuation of neointimal formation using IRE. Our study shows that IRE might
      be able to attenuate neointimal formation after angioplasty damage in a rodent
      model of restenosis. This approach may open new venues in the treatment of
      coronary artery restenosis after balloon angioplasty.

PMID- 18713697
TI  - An automatic system for the analysis and classification of human atrial
      fibrillation patterns from intracardiac electrograms.
AB  - This paper presents an automatic system for the analysis and classification of
      atrial fibrillation (AF) patterns from bipolar intracardiac signals. The system
      is made up of: 1) a feature-extraction module that defines and extracts a set of
      measures potentially useful for characterizing AF types on the basis of their
      degree of organization; 2) a feature-selection module (based on the Jeffries
      Matusita distance and a branch and bound search algorithm) identifying the best
      subset of features for discriminating different AF types; and 3) a support vector
      machine technique-based classification module that automatically discriminates
      the AF types according to the Wells' criteria. The automatic system was applied
      on 100 intracardiac AF signal strips and on a selection of 11 representative
      features, demonstrating: a) the possibility to properly identify the most
      significant features for the discrimination of AF types; b) higher accuracy
      (97.7% using the seven most informative features) than the traditional maximum
      likelihood classifier; and c) effectiveness in AF classification also with few
      training samples (accuracy = 88.3% with only five training signals). Finally, the
      system identifies a combination of indices characterizing changes of morphology
      of atrial activation waves and perturbation of the isoelectric line as the most
      effective in separating the AF types.

PMID- 18713698
TI  - Correlation between structure and resistivity variations of the live human skull.
AB  - A study on correlation between structure and resistivity variations was performed
      for live adult human skull. The resistivities of 388 skull samples, excised from
      48 skull flaps of patients undergoing surgery, were measured at body temperature
      (36.5 degrees C) using the well-known four-electrode method in the frequency
      range of 1-4 MHz. According to different structures of the skull samples, all the
      388 samples were classified into six categories and measured their resistivities:
      standard trilayer skull (7943 +/- 1752 ohm x cm, 58 samples), quasi-trilayer
      skull (14,471 +/- 3061 ohm x cm, 110 samples), standard compact skull (26,546 +/-
      5374 ohm x cm, 62 samples), quasi-compact skull (19,824 +/- 3232 ohm x cm, 53
      samples), dentate suture skull (5782 +/- 1778 ohm x cm, 41 samples), and squamous
      suture skull (12747 +/- 4120 ohm x cm, 64 samples). The results showed that the
      skull resistivities were not homogenous and were significantly influenced by
      local structural variations. The presence of sutures appeared to decrease the
      overall resistivity of particular regions largely and dentate suture decreased
      the resistivity more than squamous suture. The absence of diploe appeared to
      increase skull resistivity. The percentage on thickness of diploe would be the
      primary factor in determining the resistivity of the skull sample without suture.
      From resistivity spectra results, an inverse relationship between skull
      resistivity and signal frequency was found.

PMID- 18713699
TI  - Investigation of the cross-ratios method for point-of-gaze estimation.
AB  - The cross-ratios method for point-of-gaze (PoG) estimation uses the invariance
      property of cross-ratios in projective transformations. The inherent causes of
      the subject-dependent PoG estimation bias exhibited by this method have not been
      well characterized in the literature. Using a model of the eye and the components
      of a system (camera, light sources) that estimates PoG, a theoretical framework
      for the cross-ratios method is developed. The analysis of the cross-ratios method
      within this framework shows that the subject-dependent estimation bias is caused
      mainly by: 1) the angular deviation of the visual axis from the optic axis and 2)
      the fact that the virtual image of the pupil center is not coplanar with the
      virtual images of the light sources that illuminate the eye (corneal
      reflections). The theoretical framework provides a closed-form analytical
      expression that predicts the estimation bias as a function of subject-specific
      eye parameters. The theoretical framework also provides a clear physical
      interpretation for an existing empirically derived two-step procedure that
      compensates for the estimation bias and shows that the first step of this
      procedure is equivalent to moving the corneal reflections to a new plane that
      minimizes the distance from this plane to the virtual image of the pupil center.

PMID- 18713700
TI  - Rigorous mathematical modeling techniques for optimal delivery of macromolecules
      to the brain.
AB  - Several treatment modalities for neurodegenerative diseases or tumors of the
      central nervous system involve invasive delivery of large molecular weight drugs
      to the brain. Despite the ample record of experimental studies, accurate drug
      targeting for the human brain remains a challenge. This paper proposes a
      systematic design method of administering drugs to specific locations in the
      human brain based on first principles transport in porous media. The proposed
      mathematical framework predicts achievable treatment volumes in target regions as
      a function of brain anatomy and infusion catheter position. A systematic
      procedure to determine the optimal infusion and catheter design parameters that
      maximize the penetration depth and volumes of distribution will be discussed. The
      computer simulations are validated with agarose gel phantom experiments and rat
      data. The rigorous computational approach will allow physicians and scientists to
      better plan the administration of therapeutic drugs to the central nervous
      system.

PMID- 18713701
TI  - Electrode position scaling in realistic laplacian computation.
AB  - This note discusses the effects of the electrode position scaling on the
      realistic Laplacian (RL) computation. It is shown that when the RL is estimated
      with the help of Tikhonov regularization and the generalized cross-validation
      (GCV) criterion, improper electrode position scaling may influence the GCV
      criterion, which results in the decrease of RL precision. We identify what the
      proper scaling should be, and we provide a closer examination of how the GCV
      criterion is affected by the electrode position scaling.

PMID- 18713702
TI  - [The first 12 years of Hungarian lung transplantation].
AB  - 12 years have passed since the first Hungarian patient went through lung
      transplantation. A small but dedicated group of clinicians work to make lung
      transplantation an easily accessible, accepted therapy for Hungarian patients.
      Transplantation is recommended for patients suffering from end stage vascular or
      parenchymal diseases of the lung after conservative therapies are proven
      unsuccessful. Lung transplantation as a surgical intervention is currently not
      available in Hungary. In the past 12 years 64 Hungarian patients were
      transplanted at the Department of Cardiothoracic Surgery, Medical University of
      Vienna, in Austria by the Vienna Lung Transplant Group led by Prof. Walter
      Klepetko. Our patients went through lung transplantation for the following
      indications: cystic fibrosis (22), idiopathic lung fibrosis (18), primer
      pulmonary hypertonia (8), lymphangioleimyomatosis (5), emphysema (4) and other
      (7). The 64 patients altogether went through 68 transplantation procedures. In 4
      cases re-transplantation was necessary. The surgery techniques employed were as
      follows: bilateral lung transplantation (33), bilateral lobar transplantation
      (18), single lung transplantation (13), heart-lung transplantation (2) and split
      lung transplantation (2). Bilateral living-donor lung lobar transplantation was
      performed in one case. The mean age of patients at the time of surgery was 33.3
      years (between age 14 and 58). 48 of the 64 patients are still alive.

PMID- 18713703
TI  - [Common malformations in fetopathologic investigations between 1995 and 2006.
      Accuracy of ultrasonography confirmed by post mortem investigations].
AB  - Fetopathologic investigations are of great importance since they are aimed at
      assessing the risks of a malformation to recur in a mother's future pregnancy.
      AIMS: The authors wished to assess and analyse the accuracy of ultrasonography
      based on the results of fetopathologic investigations in view of malformations of
      higher prevalence. STUDY DESIGN: The authors have processed the details of 683
      cases affecting the nervous, cardiovascular, urinary and skeletal systems, and
      the abdominal/thoracic walls detected at our department in the period of 1995
      2006. RESULTS: No significant differences could be justified as far as the major
      statistical parameters of maternal and gestational ages at the time of the
      diagnosis were concerned. There were one or another positive detail in the
      history in a quarter of malformations affecting the central nervous,
      cardiovascular and skeletal systems and in one sixth of the cases with disorders
      of the urinary tract as well as the abdominal/thoracic wall. Urinary tract and
      cardiovascular malformations were far more common among male fetuses, while
      moderate female dominance could be observed in malformations of the central
      nervous system and of the abdominal/thoracic wall. In the four investigated
      groups of malformations, the proportion of sonographic diagnoses completely
      coinciding with the post mortem results was found to be approximately or more
      than 70%, but it was found to be much lower (38%) in urinary malformations. Based
      on the full sample, the cumulative proportion of coinciding sonographic and
      fetopathologic diagnoses were more than 63%, while completely incorrect
      ultrasonographic diagnoses amounted to 18%. CONCLUSIONS: (Even multiple)
      sonographic investigations are to be performed in a genetic centre if urinary
      tract malformation with subsequent oligohydramnion is detected. Since the
      associability of omphalocele and chromosome aberrations has been an established
      fact, and because some of the cases with omphalocele have been diagnosed as
      gastroschisis, it may be advisable to perform chromosome investigations in
      ultrasonographically diagnosed cases of gastroschisis. In cases of VSD,
      echocardiography should be performed in high-risk pregnancies even if
      ultrasonography cannot reveal any changes in the patients.

PMID- 18713704
TI  - [The use of Integra "artificial skin, dermal regeneration template" and the
      reverse radial forearm fasciocutaneous flap in the primary reconstruction of a
      septic hand injury].
AB  - Reconstruction was performed on the back of a hand following a poorly managed
      septic hand injury leading to skin and extensor apparatus necrosis using a
      reverse radial forearm fasciocutaneous flap and a bilayer artificial skin
      substitute. CASE DEMONSTRATION: Authors report on the first Hungarian case using
      Integra dermal regeneration template. Integra was placed on the back of the hand
      on an area left uncovered by the reverse radial forearm fasciocutaneous flap as
      well as on the flap harvest area. After biointegration of the regeneration
      template, the outer silicon layer was removed and a split thickness skin graft
      was applied. CONCLUSION: The take-rate on the donor area was 100% for Integra and
      99% for the skin graft, and 90% for both Integra and the skin graft on the back
      of the hand, providing a good functional and aesthetic result.

PMID- 18713705
TI  - [Hyperinsulinemic hypoglycemia in adults. Case reports and a short review].
AB  - Persistent hyperinsulinemic hypoglycemia (nesidioblastosis) not caused by an
      insulinoma is rare in adults. Morphologically no insulin secreting tumor is
      present. Keystones of diagnosis are not only low glucose levels but to maintain
      normoglycemia by use of intravenous glucose and the presence of high insulin and
      C-peptide levels. Noninvasive and invasive diagnostic techniques are required to
      rule out a hormone secreting tumor. Both conservative and/or surgical therapy are
      suggested to prevent damaging effects of repeated hypoglycemia. CASE REPORT: Two
      patients with frequent and serious episodes of hypoglycemia are reported. In the
      34-year-old female symptoms appeared with sweating, dizziness, trembling,
      nervousness and serious neuroglycopenic signs. In the 22-year-old male the main
      complaint was tympany, a rare and unusual sign of hypoglycemia, and intense
      feeling of esurience. The 24-hour fasting test was positive in both cases, i.e.
      it had to be stopped because of symptomatic hypoglycemia. No insulinoma could be
      localized, despite extensive search, therefore in both cases the diagnosis of
      adult-onset nesidioblastosis was set up, despite lack of histological
      confirmation. Diazoxide therapy resulted in symptom-free life for both patients.
      CONCLUSION: Several diagnostic methods and treatment options are suggested for
      the rare disease nesidioblastosis to balance defective insulin secretion.
      However, once the decision is made in favour of surgical therapy, there is a thin
      line between successful treatment, persistence of the disease, and pancreatic
      insufficiency. Therefore it is worth considering to try conservative therapy
      especially when surgery is of high risk. Our cases suggest that diazoxide therapy
      is an effective and safe alternative in the treatment of adult-onset
      nesidioblastosis.

PMID- 18713706
TI  - [Late postinfarction rupture of the interventricular septum].
AB  - Postinfarction ventricular septal rupture complicates 1 to 2% of cases of acute
      myocardial infarction and accounts for 5% of early mortality. This severe
      complication usually occurs within two weeks after acute myocardial infarction,
      and the elderly are more susceptible. We present a case of late rupture of the
      septum. CASE REPORT: In a 75-year-old man, a ventricular septal defect developed
      more than two months after an extensive inferoseptal myocardial infarction due to
      occlusion of the right coronary artery. After more than two months of no symptoms
      he was referred to hospital due to symptoms of right ventricle failure. The
      diagnosis was made by echocardiography, pulmonary artery catheterization and
      ventriculography. Coronarography was also performed. Intraaortic balloon pump was
      introduced and the patient was transferred to the operating room. The defect was
      repaired using a circular polytetrafluoroethylene patch supported by buttressed
      interrupted sutures from both sides. Due to significant mitral valve
      regurgitation mechanical bileaflet mitral valve was implanted with preservation
      of the entire mitral apparatus and the left descending artery was revascularized
      using a saphenous graft. CONCLUSION: This case is reported to emphasize that
      later postinfarction rupture of the ventricular septum may occur with symptoms of
      right ventricle failure dominating the clinical course.

PMID- 18713707
TI  - [Eigenfactor: a recent opportunity of measuring scientific journals].
AB  - There are various measures of a scientific journal's impact or relevance.
      Probably the best known measures based on citations are the impact factor
      published by Thomson Scientific, and the Hirsch-index created by Andras Schubert.
      Citations have long been an important way to evaluate the interest, visibility
      and impact of research, and the corresponding researchers. These ranks are very
      important for the researchers when deciding where to submit their manuscripts.
      Recently, Carl Bergstrom has suggested a new indicator called Eigenfactor.
      Eigenfactor ranks journals much as Google ranks websites. All sources consulted
      by the researcher during the research process contribute to the determination of
      the Eigenfactor. Is it possible that Eigenfactor will have the leading role in
      scientometry starting in the next century?

PMID- 18713710
TI  - [Interview with Dr. Magdolna Zajacz].

PMID- 18713711
TI  - Reliable coding of small, behaviourally relevant interaural intensity differences
      in a pair of interneurons of an insect.
AB  - Insects, as vertebrates and humans, use interaural intensity differences (IIDs)
      between the two ears for sound localization. They are remarkably sensitive for
      small IIDs of the order of 1-2dB. Here, we investigated, using an independent ear
      stimulation paradigm, how such small IIDs are reliably encoded in the binaural
      discharge differences of a prominent pair of interneurons. Starting with an IID
      of 1dB, these differences are large and significant, with the louder side being
      more strongly excited. In a comparison of simultaneous responses of left and
      right interneurons, more than 70 and 90 per cent correct responses occur at IIDs
      of 1 and 2.5dB, respectively.

PMID- 18713712
TI  - Temporal fluctuations of Y-chromosomal variation in Bos taurus.
AB  - Phylogeography has recently become more abundant in studies of demographic
      history of both wild and domestic species. A single nucleotide polymorphism (SNP)
      in the intron of the Y-chromosomal gene UTY19 displays a north-south gradient in
      modern cattle. Support for this geographical distribution of haplogroups has
      previously also been seen in ancient cattle from Germany. However, when analysing
      38 historic remains of domestic bulls and three aurochs from northern Europe for
      this SNP we found no such association. Instead, we noted extensive amounts of
      temporal variation that can be attributed to transportation of cattle and late
      breed formation.

PMID- 18713713
TI  - Sea lamprey Petromyzon marinus: an exception to the rule of homing in anadromous
      fishes.
AB  - Anadromous fishes are believed to make regular circuits of migration in the sea
      before homing to their natal rivers. Sea lamprey Petromyzon marinus is an
      anadromous fish that is an exception to this life-history pattern. It also
      differs from other anadromous fishes in that its adult phase is parasitic, a
      feeding strategy that should make homing problematic for lamprey cohorts that
      become widely dispersed through transport by the diverse hosts they parasitize.
      We sequenced a portion of the mitochondrial DNA control region from sea lampreys
      collected from 11 North American east coast rivers to test for genetic evidence
      of homing. There were no significant differences (chi2=235.1, p=0.401) in
      haplotype frequencies among them, with almost 99 per cent of haplotypic diversity
      occurring within populations. These findings, together with concordant genetic
      results from other geographical regions and ancillary information on pheromonal
      communication, suggest that sea lamprey does not home but rather exhibits
      regional panmixia while using a novel 'suitable river' strategy to complete its
      life cycle.

PMID- 18713714
TI  - Neighbourhood density and genetic relatedness interact to determine fruit set and
      abortion rates in a continuous tropical tree population.
AB  - Tropical trees may show positive density dependence in fruit set and maturation
      due to pollen limitation in low-density populations. However, pollen from closely
      related individuals in the local neighbourhood might reduce fruit set or increase
      fruit abortion in self-incompatible tree species. We investigated the role of
      neighbourhood density and genetic relatedness on individual fruit set and
      abortion in the neotropical tree Jacaranda copaia in a large forest plot in
      central Panama. Using nested neighbourhood models, we found a strong positive
      effect of increased conspecific density on fruit set and maturation. However,
      high neighbourhood genetic relatedness interacted with density to reduce total
      fruit set and increase the proportion of aborted fruit. Our results imply a
      fitness advantage for individuals growing in high densities as measured by fruit
      set, but realized fruit set is lowered by increased neighbourhood relatedness. We
      hypothesize that the mechanism involved is increased visitation by density
      dependent invertebrate pollinators in high-density populations, which increases
      pollen quantity and carry-over and increases fruit set and maturation, coupled
      with self-incompatibility at early and late stages due to biparental inbreeding
      that lowers fruit set and increases fruit abortion. Implications for the
      reproductive ecology and conservation of tropical tree communities in continuous
      and fragmented habitats are discussed.

PMID- 18713715
TI  - Birds are tracking climate warming, but not fast enough.
AB  - Range shifts of many species are now documented as a response to global warming.
      But whether these observed changes are occurring fast enough remains uncertain
      and hardly quantifiable. Here, we developed a simple framework to measure change
      in community composition in response to climate warming. This framework is based
      on a community temperature index (CTI) that directly reflects, for a given
      species assemblage, the balance between low- and high-temperature dwelling
      species. Using data from the French breeding bird survey, we first found a strong
      increase in CTI over the last two decades revealing that birds are rapidly
      tracking climate warming. This increase corresponds to a 91 km northward shift in
      bird community composition, which is much higher than previous estimates based on
      changes in species range edges. During the same period, temperature increase
      corresponds to a 273 km northward shift in temperature. Change in community
      composition was thus insufficient to keep up with temperature increase: birds are
      lagging approximately 182 km behind climate warming. Our method is applicable to
      any taxa with large-scale survey data, using either abundance or occurrence data.
      This approach can be further used to test whether different delays are found
      across groups or in different land-use contexts.

PMID- 18713716
TI  - Latitudinal gradients in sea ice and primary production determine Arctic seabird
      colony size in Greenland.
AB  - Sea ice loss will indirectly alter energy transfer through the pelagic food web
      and ultimately impact apex predators. We quantified spring-time trends in sea ice
      recession around each of 46 thick-billed murre (Uria lomvia) colonies in west
      Greenland across 20 degrees of latitude and investigated the magnitude and timing
      of the associated spring-time primary production. A geographical information
      system was used to extract satellite-based observations of sea ice concentration
      from the Nimbus-7 scanning multichannel microwave radiometer (SMMR, 1979-1987)
      and the Defence Meteorological Satellite Programs Special Sensor Microwave/Imager
      (SSMI, 1987-2004), and satellite-based observations of chlorophyll a from the
      moderate resolution imaging spectroradiometer (MODIS: EOS-Terra satellite) in
      weekly intervals in circular buffers around each colony site (150 km in radius).
      Rapid recession of high Arctic seasonal ice cover created a temporally
      predictable primary production bloom and associated trophic cascade in water
      gradually exposed to solar radiation. This pattern was largely absent from lower
      latitudes where little to no sea ice resulted in a temporally variable primary
      production bloom driven by nutrient cycling and upwelling uncoupled to ice. The
      relationship between the rate and variability of sea ice recession and colony
      size of thick-billed murres shows that periodical confinement of the trophic
      cascade at high latitudes determines the carrying capacity for Arctic seabirds
      during the breeding period.

PMID- 18713717
TI  - In your face: facial metrics predict aggressive behaviour in the laboratory and
      in varsity and professional hockey players.
AB  - Facial characteristics are an important basis for judgements about gender,
      emotion, personality, motivational states and behavioural dispositions. Based on
      a recent finding of a sexual dimorphism in facial metrics that is independent of
      body size, we conducted three studies to examine the extent to which individual
      differences in the facial width-to-height ratio were associated with trait
      dominance (using a questionnaire) and aggression during a behavioural task and in
      a naturalistic setting (varsity and professional ice hockey). In study 1, men had
      a larger facial width-to-height ratio, higher scores of trait dominance, and were
      more reactively aggressive compared with women. Individual differences in the
      facial width-to-height ratio predicted reactive aggression in men, but not in
      women (predicted 15% of variance). In studies 2 (male varsity hockey players) and
      3 (male professional hockey players), individual differences in the facial width
      to-height ratio were positively related to aggressive behaviour as measured by
      the number of penalty minutes per game obtained over a season (predicted 29 and
      9% of the variance, respectively). Together, these findings suggest that the
      sexually dimorphic facial width-to-height ratio may be an 'honest signal' of
      propensity for aggressive behaviour.

PMID- 18713718
TI  - Life in a temperate Polar sea: a unique taphonomic window on the structure of a
      Late Cretaceous Arctic marine ecosystem.
AB  - As the earth faces a warming climate, the rock record reminds us that comparable
      climatic scenarios have occurred before. In the Late Cretaceous, Arctic marine
      organisms were not subject to frigid temperatures but still contended with
      seasonal extremes in photoperiod. Here, we describe an unusual fossil assemblage
      from Devon Island, Arctic Canada, that offers a snapshot of a ca 75 Myr ago
      marine palaeoecosystem adapted to such conditions. Thick siliceous biogenic
      sediments and glaucony sands reveal remarkably persistent high primary
      productivity along a high-latitude Late Cretaceous coastline. Abundant fossil
      faeces demonstrate that this planktonic bounty supported benthic invertebrates
      and large, possibly seasonal, vertebrates in short food chains. These ancient
      organisms filled trophic roles comparable to those of extant Arctic species, but
      there were fundamental differences in resource dynamics. Whereas most of the
      modern Arctic is oligotrophic and structured by resources from melting sea ice,
      we suggest that forested terrestrial landscapes helped support the ancient marine
      community through high levels of terrigenous organic input.

PMID- 18713719
TI  - A new cytogenetic mechanism for bacterial endosymbiont-induced parthenogenesis in
      Hymenoptera.
AB  - Vertically transmitted endosymbiotic bacteria, such as Wolbachia, Cardinium and
      Rickettsia, modify host reproduction in several ways to facilitate their own
      spread. One such modification results in parthenogenesis induction, where males,
      which are unable to transmit the bacteria, are not produced. In Hymenoptera, the
      mechanism of diploidization due to Wolbachia infection, known as gamete
      duplication, is a post-meiotic modification. During gamete duplication, the
      meiotic mechanism is normal, but in the first mitosis the anaphase is aborted.
      The two haploid sets of chromosomes do not separate and thus result in a single
      nucleus containing two identical sets of haploid chromosomes. Here, we outline an
      alternative cytogenetic mechanism for bacterial endosymbiont-induced
      parthenogenesis in Hymenoptera. During female gamete formation in Rickettsia
      infected Neochrysocharis formosa (Westwood) parasitoids, meiotic cells undergo
      only a single equational division followed by the expulsion of a single polar
      body. This absence of meiotic recombination and reduction corresponds well with a
      non-segregation pattern in the offspring of heterozygous females. We conclude
      that diploidy in N. formosa is maintained through a functionally apomictic
      cloning mechanism that differs entirely from the mechanism induced by Wolbachia.

PMID- 18713720
TI  - Competing phytoplankton undermines allelopathy of a bloom-forming dinoflagellate.
AB  - Biotic interactions in the plankton can be both complex and dynamic. Competition
      among phytoplankton is often chemically mediated, but no studies have considered
      whether allelopathic compounds are modified by biotic interactions. Here, we show
      that compounds exuded during Karenia brevis blooms were allelopathic to the
      cosmopolitan diatom Skeletonema costatum, but that bloom allelopathy varied
      dramatically among collections and years. We investigated several possible causes
      of this variability and found that neither bloom density nor concentrations of
      water-borne brevetoxins correlated with allelopathic potency. However, when we
      directly tested whether the presence of competing phytoplankton influenced bloom
      allelopathy, we found that S. costatum reduced the growth-inhibiting effects of
      bloom exudates, suggesting that S. costatum has a mechanism for undermining K.
      brevis allelopathy. Additional laboratory experiments indicated that inducible
      changes to K. brevis allelopathy were restricted to two diatoms among five
      sensitive phytoplankton species, whereas five other species were constitutively
      resistant to K. brevis allelopathy. Our results suggest that competitors differ
      in their responses to phytoplankton allelopathy, with S. costatum exhibiting a
      previously undescribed method of resistance that may influence community
      structure and alter bloom dynamics.

PMID- 18713721
TI  - Testing the island effect in adaptive radiation: rates and patterns of
      morphological diversification in Caribbean and mainland Anolis lizards.
AB  - Many of the classic examples of adaptive radiation, including Caribbean Anolis
      lizards, are found on islands. However, Anolis also exhibits substantial species
      richness and ecomorphological disparity on mainland Central and South America. We
      compared patterns and rates of morphological evolution to investigate whether, in
      fact, island Anolis are exceptionally diverse relative to their mainland
      counterparts. Quite the contrary, we found that rates and extent of
      diversification were comparable--Anolis adaptive radiation is not an island
      phenomenon. However, mainland and Caribbean anoles occupy different parts of
      morphological space; in independent colonizations of both island and mainland
      habitats, island anoles have evolved shorter limbs and better-developed toe pads.
      These patterns suggest that the two areas are on different evolutionary
      trajectories. The ecological causes of these differences are unknown, but may
      relate to differences in predation or competition among mainland and island
      communities.

PMID- 18713722
TI  - A latitudinal cline in the Chinook salmon (Oncorhynchus tshawytscha) Clock gene:
      evidence for selection on PolyQ length variants.
AB  - A critical seasonal event for anadromous Chinook salmon (Oncorhynchus
      tshawytscha) is the time at which adults migrate from the ocean to breed in
      freshwater. We investigated whether allelic variation at the circadian rhythm
      genes, OtsClock1a and OtsClock1b, underlies genetic control of migration timing
      among 42 populations in North America. We identified eight length variants of the
      functionally important polyglutamine repeat motif (PolyQ) of OtsClock1b while
      OtsClock1a PolyQ was highly conserved. We found evidence of a latitudinal cline
      in average allele length and frequency of the two most common OtsClock1b alleles.
      The shorter 335 bp allele increases in frequency with decreasing latitude while
      the longer 359 bp allele increases in frequency at higher latitudes. Comparison
      to 13 microsatellite loci showed that 335 and 359 bp deviate significantly from
      neutral expectations. Furthermore, a hierarchical gene diversity analysis based
      on OtsClock1b PolyQ variation revealed that run timing explains 40.9 per cent of
      the overall genetic variance among populations. By contrast, an analysis based on
      13 microsatellite loci showed that run timing explains only 13.2 per cent of the
      overall genetic variance. Our findings suggest that length polymorphisms in
      OtsClock1b PolyQ may be maintained by selection and reflect an adaptation to
      ecological factors correlated with latitude, such as the seasonally changing day
      length.

PMID- 18713723
TI  - The effect of opinion clustering on disease outbreaks.
AB  - Many high-income countries currently experience large outbreaks of vaccine
      preventable diseases such as measles despite the availability of highly effective
      vaccines. This phenomenon lacks an explanation in countries where vaccination
      rates are rising on an already high level. Here, we build on the growing evidence
      that belief systems, rather than access to vaccines, are the primary barrier to
      vaccination in high-income countries, and show how a simple opinion formation
      process can lead to clusters of unvaccinated individuals, leading to a dramatic
      increase in disease outbreak probability. In particular, the effect of clustering
      on outbreak probabilities is strongest when the vaccination coverage is close to
      the level required to provide herd immunity under the assumption of random
      mixing. Our results based on computer simulations suggest that the current
      estimates of vaccination coverage necessary to avoid outbreaks of vaccine
      preventable diseases might be too low.

PMID- 18713724
TI  - Vascular cells contribute to atherosclerosis by cytokine- and innate-immunity
      related inflammatory mechanisms.
AB  - Cardiovascular diseases are the human diseases with the highest death rate and
      atherosclerosis is one of the major underlying causes of cardiovascular diseases.
      Inflammatory and innate immune mechanisms, employing monocytes, innate receptors,
      innate cytokines, or chemokines are suggested to be involved in atherogenesis.
      Among the inflammatory pathways the cytokines are central players. Plasma levels
      of cytokines and related proteins, such as CRP, have been investigated in
      cardiovascular patients, tissue mRNA expression was analyzed and correlations to
      vascular diseases established. Consistent with these findings the generation of
      cytokine-deficient animals has provided direct evidence for a role of cytokines
      in atherosclerosis. In vitro cell culture experiments further support the
      suggestion that cytokines and other innate mechanisms contribute to
      atherogenesis. Among the initiation pathways of atherogenesis are innate
      mechanisms, such as toll-like-receptors (TLRs), including the endotoxin receptor
      TLR4. On the other hand, innate cytokines, such as IL-1 or TNF, or even
      autoimmune triggers may activate the cells. Cytokines potently activate multiple
      functions relevant to maintain or spoil homeostasis within the vessel wall.
      Vascular cells, not least smooth muscle cells, can actively contribute to the
      inflammatory cytokine-dependent network in the blood vessel wall by: (i)
      production of cytokines; (ii) response to these potent cell activators; and (iii)
      cytokine-mediated interaction with invading cells, such as monocytes, T-cells, or
      mast cells. Activation of these pathways results in accumulation of cells and
      increased LDL- and ECM-deposition which may serve as an 'immunovascular memory'
      resulting in an ever-growing response to subsequent invasions. Thus, vascular
      cells may potently contribute to the inflammatory pathways involved in
      development and acceleration of atherosclerosis.

PMID- 18713725
TI  - Removal of immune-stimulatory components from surfaces by plasma discharges.
AB  - Immune-stimulating microbiological components like lipopolysaccharide (LPS),
      lipoteichoic acid (LTA) and zymosan bound onto surfaces lead to severe problems
      when brought in contact with the organism via surgical instruments or implants.
      We have shown, in recent studies, that it is possible to detect different immune
      stimulating components directly on the surface, via an indirect detection method,
      using human whole-blood and the monocyte reaction to measure the inflammatory
      mediator release (IL-1beta) by ELISA. With regard to the inactivation of
      pyrogenic substances, we present a method based on the application of a low
      pressure microwave plasma discharge working at low temperatures. We found a fast
      (10 s to a few minutes) removal rate of the immune-stimulating competence for
      LPS, LTA and zymosan. To mimic the bacterial cell-wall, LPS in combination with
      muramyl dipeptide was employed and the decreasing rate of the inflammatory signal
      did not differ from pure LPS.

PMID- 18713726
TI  - Lipopolysaccharide (LPS) of Porphyromonas gingivalis induces IL-1beta, TNF-alpha
      and IL-6 production by THP-1 cells in a way different from that of Escherichia
      coli LPS.
AB  - Lipopolysaccharide (LPS) derived from the periodontal pathogen Porphyromonas
      gingivalis has been shown to differ from enterobacterial LPS in structure and
      function; therefore, the Toll-like receptors (TLRs) and the intracellular
      inflammatory signaling pathways are accordingly different. To elucidate the
      signal transduction pathway of P. gingivalis, LPS-induced pro-inflammatory
      cytokine production in the human monocytic cell line THP-1 was measured by ELISA,
      and the TLRs were determined by the blocking test using anti-TLRs antibodies. In
      addition, specific inhibitors as well as Phospho-ELISA kits were used to analyze
      the intracellular signaling pathways. Escherichia coli LPS was used as the
      control. In this study, P. gingivalis LPS showed the ability to induce cytokine
      production in THP-1 cells and its induction was significantly (P < 0.05)
      suppressed by anti-TLR2 antibody or JNK inhibitor, and the phosphorylation level
      of JNK was significantly increased (P < 0.05). These results indicate that TLR2
      JNK is the main signaling pathway of P. gingivalis LPS-induced cytokine
      production, while the cytokine induction by E. coli LPS was mainly via TLR4-NF
      kappaB and TLR4-p38MAPK. This suggests that P. gingivalis LPS differs from E.
      coli LPS in its signaling pathway in THP-1 cells, and that the TLR2-JNK pathway
      might play a significant role in P. gingivalis LPS-induced chronic inflammatory
      periodontal disease.

PMID- 18713727
TI  - Interleukin-10 inhibits tumor necrosis factor-alpha production in
      lipopolysaccharide-stimulated RAW 264.7 cells through reduced MyD88 expression.
AB  - The mechanism of interleukin (IL)-10-mediated inhibition of tumor necrosis factor
      (TNF)-alpha production was studied by lipopolysaccharide (LPS)-stimulated RAW
      264.7 macrophage cells. IL-10 inhibited TNF-alpha production transiently at an
      early stage after LPS stimulation. IL-10 inhibited the activation of nuclear
      factor (NF)-kappaB, p38 and stress-activated protein kinase (SAPK) in LPS
      stimulated RAW 264.7 cells. Although the level of MyD88 protein increased in
      response to LPS, IL-10 prevented the LPS-induced MyD88 augmentation. There was no
      significant difference in the MyD88 mRNA expression between the cells pretreated
      with or without IL-10 in response to LPS. Therefore, IL-10 was suggested to
      inhibit LPS-induced TNF-alpha production via reduced MyD88 expression.

PMID- 18713728
TI  - Mice deficient in the CXCR2 ligand, CXCL1 (KC/GRO-alpha), exhibit increased
      susceptibility to dextran sodium sulfate (DSS)-induced colitis.
AB  - The role of TLRs and MyD88 in the maintenance of gut integrity in response to
      dextran sodium sulfate (DSS)-induced colitis was demonstrated recently and led to
      the conclusion that the innate immune response to luminal commensal flora
      provides necessary signals that facilitate epithelial repair and permits a return
      to homeostasis after colonic injury. In this report, we demonstrate that a
      deficit in a single neutrophil chemokine, CXCL1/KC, also results in a greatly
      exaggerated response to DSS. Mice with a targeted mutation in the gene that
      encodes this chemokine responded to 2.5% DSS in their drinking water with
      significant weight loss, bloody stools, and a complete loss of gut integrity in
      the proximal and distal colon, accompanied by a predominantly mononuclear
      infiltrate, with few detectable neutrophils. In contrast, CXCL1/KC(- /-) and wild
      type C57BL/6J mice provided water showed no signs of inflammation and, at this
      concentration of DSS, wild-type mice showed only minimal histopathology, but
      significantly more infiltrating neutrophils. This finding implies that neutrophil
      infiltration induced by CXCL1/KC is an essential component of the intestinal
      response to inflammatory stimuli as well as the ability of the intestine to
      restore mucosal barrier integrity.

PMID- 18713729
TI  - Some assembly required: putting the epithelial sodium channel together.

PMID- 18713730
TI  - The single subunit transmembrane E3 ligase gene related to anergy in lymphocytes
      (GRAIL) captures and then ubiquitinates transmembrane proteins across the cell
      membrane.
AB  - The ubiquitin E3 ligase gene related to anergy in lymphocytes (GRAIL) (Rnf128) is
      a type 1 transmembrane protein that induces T cell anergy through the
      ubiquitination activity of its cytosolic RING finger. GRAIL also contains an
      equally large luminal region consisting primarily of an uncharacterized protease
      associated (PA) domain. Using two-hybrid technology to screen for proteins that
      bound the PA domain we identified CD151, a member of the tetraspanin family of
      membrane proteins. GRAIL bound to the luminal/extracellular portion of both CD151
      and the related tetraspanin CD81 using its PA domain, which promoted
      ubiquitination of cytosolic lysine residues. GRAIL exhibited specificity for
      lysines only within the tetraspanin amino terminus even in the presence of other
      cytosolic lysine residues in the substrate. GRAIL-mediated ubiquitination
      promoted proteasomal degradation and cell surface down-regulation of tetraspanins
      via Lys-48 linkages. As a result, the juxtaposition of PA and RING finger domains
      across a lipid bilayer facilitates the capture of transmembrane substrates for
      subsequent ubiquitination. These findings identify for the first time a single
      subunit E3 ligase containing a substrate-binding domain spatially restricted by a
      membrane from its E2 recruitment domain as well as an E3 ligase for members of
      the tetraspanin family.

PMID- 18713731
TI  - Activation-dependent hindrance of photoreceptor G protein diffusion by lipid
      microdomains.
AB  - The dynamics of G protein-mediated signal transduction depend on the two
      dimensional diffusion of membrane-bound G proteins and receptors, which has been
      suggested to be rate-limiting for vertebrate phototransduction, a highly
      amplified G protein-coupled signaling pathway. Using fluorescence recovery after
      photobleaching (FRAP), we measured the diffusion of the G protein transducin
      alpha-subunit (Galpha(t)) and the G protein-coupled receptor rhodopsin on disk
      membranes of living rod photoreceptors from transgenic Xenopus laevis. Treatment
      with either methyl-beta-cyclodextrin or filipin III to disrupt cholesterol
      containing lipid microdomains dramatically accelerated diffusion of Galpha(t) in
      its GTP-bound state and of the rhodopsin-Galphabetagamma(t) complex but not of
      rhodopsin or inactive GDP-bound Galphabetagamma. These results imply an activity
      dependent sequestration of G proteins into cholesterol-dependent lipid
      microdomains, which limits diffusion and exclude the majority of free rhodopsin
      and the free G protein heterotrimer. Our data offer a novel demonstration of
      lipid microdomains in the internal membranes of living sensory neurons.

PMID- 18713732
TI  - Flavin nucleotide metabolism in plants: monofunctional enzymes synthesize fad in
      plastids.
AB  - FAD synthetases (EC 2.7.7.2) catalyze biosynthesis of FAD from FMN and ATP.
      Monofunctional FAD synthetases are known to exist in mammals and yeast;
      bifunctional enzymes also catalyzing phosphorylation of riboflavin to FMN are
      known to exist in bacteria. Previously known eukaryotic enzymes with FAD
      synthetase activity have no sequence similarity to prokaryotic enzymes with
      riboflavin kinase and FAD synthetase activities. Proteins homologous to bacterial
      bifunctional FAD synthetases, yet shorter and lacking amino acid motifs at the C
      terminus, were found by bioinformatic analyses in vascular plant genomes,
      suggesting that plants contain a type of FAD synthetase previously known to exist
      only in prokaryotes. The Arabidopsis thaliana genome encodes two of such
      proteins. Both proteins, which we named AtRibF1 and AtRibF2, carry N-terminal
      extensions with characteristics of organellar targeting peptides. AtRibF1 and
      AtRibF2 cDNAs were cloned by reverse transcription-PCR. Only FAD synthetase
      activity was detected in the recombinant enzymes produced in Escherichia coli.
      FMN and ATP inhibited both enzymes. Kinetic parameters of AtRibF1 and AtRibF2 for
      the two substrates were similar. Confocal microscopy of protoplasts transformed
      with enhanced green fluorescence protein-fused proteins showed that AtRibF1 and
      AtRibF2 are targeted to plastids. In agreement with subcellular localization to
      plastids, Percoll-isolated chloroplasts from pea (Pisum sativum) synthesized FAD
      from imported riboflavin. Riboflavin kinase, FMN hydrolase, and FAD
      pyrophosphatase activities were detected in Percoll-isolated chloroplasts and
      mitochondria from pea. We propose from these new findings a model for subcellular
      distribution of enzymes that synthesize and hydrolyze flavin nucleotides in
      plants.

PMID- 18713733
TI  - On the mechanism of quinol oxidation at the QP site in the cytochrome bc1
      complex: studied using mutants lacking cytochrome bL or bH.
AB  - To elucidate the mechanism of bifurcated oxidation of quinol in the cytochrome
      bc1 complex, Rhodobacter sphaeroides mutants, H198N and H111N, lacking heme bL
      and heme bH, respectively, were constructed and characterized. Purified mutant
      complexes have the same subunit composition as that of the wild-type complex, but
      have only 9-11% of the electron transfer activity, which is sensitive to
      stigmatellin or myxothiazol. The Em values for hemes bL and bH in the H111N and
      H198N complexes are -95 and -35 mV, respectively. The pseudo first-order
      reduction rate constants for hemes bL and bH in H111N and H198N, by ubiquiniol,
      are 16.3 and 12.4 s(-1), respectively. These indicate that the Qp site in the
      H111N mutant complex is similar to that in the wild-type complex. Pre-steady
      state reduction rates of heme c1 by these two mutant complexes decrease to a
      similar extent of their activity, suggesting that the decrease in electron
      transfer activity is due to impairment of movement of the head domain of reduced
      iron-sulfur protein, caused by disruption of electron transfer from heme bL to
      heme bH. Both mutant complexes produce as much superoxide as does antimycin A
      treated wild-type complex. Ascorbate eliminates all superoxide generating
      activity in the intact or antimycin inhibited wild-type or mutant complexes.

PMID- 18713734
TI  - Metalloproteinase- and gamma-secretase-mediated cleavage of protein-tyrosine
      phosphatase receptor type Z.
AB  - Protein-tyrosine phosphatase receptor type Z (Ptprz) is preferentially expressed
      in the brain as a major chondroitin sulfate proteoglycan. Three splicing
      variants, two receptor isoforms and one secretory isoform, are known. Here, we
      show that the extracellular region of the receptor isoforms of Ptprz are cleaved
      by metalloproteinases, and subsequently the membrane-tethered fragment is cleaved
      by presenilin/gamma-secretase, releasing its intracellular region into the
      cytoplasm; of note, the intracellular fragment of Ptprz shows nuclear
      localization. Administration of GM6001, an inhibitor of metalloproteinases, to
      mice demonstrated the metalloproteinase-mediated cleavage of Ptprz under
      physiological conditions. Furthermore, we identified the cleavage sites in the
      extracellular juxtamembrane region of Ptprz by tumor necrosis factor-alpha
      converting enzyme and matrix metalloproteinase 9. This is the first evidence of
      the metalloproteinase-mediated processing of a receptor-like protein-tyrosine
      phosphatase in the central nervous system.

PMID- 18713735
TI  - Mitochondrial metabolism modulates differentiation and teratoma formation
      capacity in mouse embryonic stem cells.
AB  - Relatively little is known regarding the role of mitochondrial metabolism in stem
      cell biology. Here we demonstrate that mouse embryonic stem cells sorted for low
      and high resting mitochondrial membrane potential (DeltaPsi(m)L and DeltaPsi(m)H)
      are indistinguishable morphologically and by the expression of pluripotency
      markers, whereas markedly differing in metabolic rates. Interestingly,
      DeltaPsi(m)L cells are highly efficient at in vitro mesodermal differentiation
      yet fail to efficiently form teratomas in vivo, whereas DeltaPsi(m)H cells behave
      in the opposite fashion. We further demonstrate that DeltaPsi(m) reflects the
      degree of overall mammalian target of rapamycin (mTOR) activation and that the
      mTOR inhibitor rapamycin reduces metabolic rate, augments differentiation, and
      inhibits tumor formation of the mouse embryonic stem cells with a high metabolic
      rate. Taken together, our results suggest a coupling between intrinsic metabolic
      parameters and stem cell fate that might form a basis for novel enrichment
      strategies and therapeutic options.

PMID- 18713736
TI  - The acidic domain of GPIHBP1 is important for the binding of lipoprotein lipase
      and chylomicrons.
AB  - GPIHBP1, a glycosylphosphatidylinositol-anchored endothelial cell protein of the
      lymphocyte antigen 6 (Ly6) family, plays a key role in the lipolysis of
      triglyceride-rich lipoproteins (e.g. chylomicrons). GPIHBP1 is expressed along
      the luminal surface of endothelial cells of heart, skeletal muscle, and adipose
      tissue, and GPIHBP1-expressing cells bind lipoprotein lipase (LPL) and
      chylomicrons avidly. GPIHBP1 contains an amino-terminal acidic domain (amino
      acids 24-48) that is enriched in aspartate and glutamate residues, and we
      previously speculated that this domain might be important in binding ligands. To
      explore the functional importance of the acidic domain, we tested the ability of
      polyaspartate or polyglutamate peptides to block the binding of ligands to pgsA
      745 Chinese hamster ovary cells that overexpress GPIHBP1. Both polyaspartate and
      polyglutamate blocked LPL and chylomicron binding to GPIHBP1. Also, a rabbit
      antiserum against the acidic domain of GPIHBP1 blocked LPL and chylomicron
      binding to GPIHBP1-expressing cells. Replacing the acidic amino acids within
      GPIHBP1 residues 38-48 with alanine eliminated the ability of GPIHBP1 to bind LPL
      and chylomicrons. Finally, mutation of the positively charged heparin-binding
      domains within LPL and apolipoprotein AV abolished the ability of these proteins
      to bind to GPIHBP1. These studies indicate that the acidic domain of GPIHBP1 is
      important and that electrostatic interactions play a key role in ligand binding.

PMID- 18713737
TI  - Vibrio vulnificus rpoS expression is repressed by direct binding of cAMP-cAMP
      receptor protein complex to its two promoter regions.
AB  - Vibrio vulnificus, a septicemia-causing pathogenic bacterium, acquires resistance
      against various stresses and expresses virulence factors via an rpoS gene
      product. In this study, we investigated the transcriptional characteristics of
      this global regulator. Two distinct transcriptional initiation sites for the rpoS
      gene, the proximal promoter (P(p)) and the distal promoter (P(d)), were defined
      by primer extension experiments. Various rpoS::luxAB transcriptional fusions
      indicated that P(d) is a major promoter of rpoS expression. Western blot analysis
      showed that RpoS levels were inversely correlated with intracellular levels of
      3',5'-cyclic AMP (cAMP). The expressions of both P(d) and P(p) were increased in
      cya and crp mutants. The exogenous addition of cAMP to the cya mutant resulted in
      repressed expression of rpoS. In addition, rpoS expression was significantly
      lowered in the cpdA mutant, in which the level of cAMP was elevated because of
      the absence of 3',5'-cAMP phosphodiesterase. In vitro transcription assays using
      the V. vulnificus RNA polymerase showed that the transcripts from both promoters
      were reduced by addition of the cAMP-cAMP receptor protein (CRP). The cAMP-CRP
      was shown to bind to two rpoS promoters by electrophoretic mobility shift assays.
      The alteration of the putative CRP-binding site on each rpoS promoter, via site
      directed mutagenesis, abolished the binding of cAMP-CRP as well as regulation by
      cAMP-CRP. Therefore, this study shows a relationship between the level of
      intracellular cAMP and the degree of rpoS expression and further demonstrates,
      for the first time, the direct binding of the cAMP-CRP complex to rpoS upstream
      regions, which results in repression of rpoS gene expression.

PMID- 18713738
TI  - Phosphorylation of the yeast nitrate transporter Ynt1 is essential for delivery
      to the plasma membrane during nitrogen limitation.
AB  - Ynt1 is the sole high affinity nitrate transporter of the yeast Hansenula
      polymorpha. It is highly regulated by the nitrogen source, by being down
      regulated in response to glutamine by repression of the YNT1 gene and Ynt1
      ubiquitinylation, endocytosis, and vacuolar degradation. On the contrary, we show
      that nitrogen limitation stabilizes Ynt1 levels at the plasma membrane, requiring
      phosphorylation of the transporter. We determined that Ser-246 in the central
      intracellular loop plays a key role in the phosphorylation of Ynt1 and that the
      nitrogen permease reactivator 1 kinase (Npr1) is necessary for Ynt1
      phosphorylation. Abolition of phosphorylation led Ynt1 to the vacuole by a pep12
      dependent end4-independent pathway, which is also dependent on ubiquitinylation,
      whereas Ynt1 protein lacking ubiquitinylation sites does not follow this pathway.
      We found that, under nitrogen limitation, Ynt1 phosphorylation is essential for
      rapid induction of nitrate assimilation genes. Our results suggest that, under
      nitrogen limitation, phosphorylation prevents Ynt1 delivery from the secretion
      route to the vacuole, which, aided by reduced ubiquitinylation, accumulates Ynt1
      at the plasma membrane. This mechanism could be part of the response that allows
      nitrate-assimilatory organisms to cope with nitrogen depletion.

PMID- 18713739
TI  - TNFR1 promotes tumor necrosis factor-mediated mouse colon epithelial cell
      survival through RAF activation of NF-kappaB.
AB  - Tumor necrosis factor (TNF) is a therapeutic target in the treatment of
      inflammatory bowel disease; however, the exact role of TNF signaling in the colon
      epithelium remains unclear. We demonstrate that TNF activation of TNF receptor
      (R)1 stimulates both pro- and anti-apoptotic signaling pathways in the colon
      epithelium; however, TNFR1 protects against colon epithelial cell apoptosis
      following TNF exposure. To investigate anti-apoptotic signaling pathways
      downstream of TNFR1, we generated an intestinal epithelium-specific Raf knock-out
      mouse and identified Raf kinase as a key regulator of colon epithelial cell
      survival in response to TNF. Surprisingly, Raf promotes NF-kappaB p65
      phosphorylation, independent of MEK signaling, to support cell survival. Taken
      together, these data demonstrate a novel pathway in which Raf promotes colon
      epithelial cell survival through NF-kappaB downstream of TNFR1 activation. Thus,
      further understanding of colon epithelial cell-specific TNFR signaling may result
      in the identification of new targets for inflammatory bowel disease treatment and
      define novel mediators of colitis-associated cancer.

PMID- 18713740
TI  - Structure of protein geranylgeranyltransferase-I from the human pathogen Candida
      albicans complexed with a lipid substrate.
AB  - Protein geranylgeranyltransferase-I (GGTase-I) catalyzes the transfer of a 20
      carbon isoprenoid lipid to the sulfur of a cysteine residue located near the C
      terminus of numerous cellular proteins, including members of the Rho superfamily
      of small GTPases and other essential signal transduction proteins. In humans,
      GGTase-I and the homologous protein farnesyltransferase (FTase) are targets of
      anticancer therapeutics because of the role small GTPases play in oncogenesis.
      Protein prenyltransferases are also essential for many fungal and protozoan
      pathogens that infect humans, and have therefore become important targets for
      treating infectious diseases. Candida albicans, a causative agent of systemic
      fungal infections in immunocompromised individuals, is one pathogen for which
      protein prenylation is essential for survival. Here we present the crystal
      structure of GGTase-I from C. albicans (CaGGTase-I) in complex with its cognate
      lipid substrate, geranylgeranylpyrophosphate. This structure provides a high
      resolution picture of a non-mammalian protein prenyltransferase. There are
      significant variations between species in critical areas of the active site,
      including the isoprenoid-binding pocket, as well as the putative product exit
      groove. These differences indicate the regions where specific protein
      prenyltransferase inhibitors with antifungal activity can be designed.

PMID- 18713741
TI  - Human IgG2 antibody disulfide rearrangement in vivo.
AB  - Proteins destined to circulate in the blood are first folded and assembled in the
      endoplasmic reticulum of secretory cells. For antibodies, like many other serum
      proteins, the folding and assembly steps involve the formation of disulfide
      bonds. Such bonds have been thought to be static features of proteins,
      stabilizing domains, and linking polypeptide chains, although some cases of
      extracellular disulfide bond cleavage have been noted. Recently, the human IgG2
      antibody subclass was found to possess multiple structures differing in specific
      disulfide linkages. These structures are naturally occurring and can, in some
      cases, affect the activity of the antibody. Here we show that these IgG2
      disulfide linkages interconvert while circulating in humans. Secretory cells
      initially produce primarily one form (IgG2-A), which is rapidly converted to a
      second form (IgG2-A/B) while circulating in the blood, followed by a slower
      conversion to a third form (IgG2-B). This work demonstrates that the disulfide
      structure of the IgG2 antibody is dynamic in vivo, on a time scale similar to
      that of the protein's lifetime. Thus, changes to the IgG2 disulfide structure
      provide a marker of the protein's age and may alter its activity over its
      lifetime.

PMID- 18713742
TI  - Structure of human J-type co-chaperone HscB reveals a tetracysteine metal-binding
      domain.
AB  - Iron-sulfur proteins play indispensable roles in a broad range of biochemical
      processes. The biogenesis of iron-sulfur proteins is a complex process that has
      become a subject of extensive research. The final step of iron-sulfur protein
      assembly involves transfer of an iron-sulfur cluster from a cluster-donor to a
      cluster-acceptor protein. This process is facilitated by a specialized chaperone
      system, which consists of a molecular chaperone from the Hsc70 family and a co
      chaperone of the J-domain family. The 3.0 A crystal structure of a human
      mitochondrial J-type co-chaperone HscB revealed an L-shaped protein that
      resembles Escherichia coli HscB. The important difference between the two
      homologs is the presence of an auxiliary metal-binding domain at the N terminus
      of human HscB that coordinates a metal via the tetracysteine consensus motif
      CWXCX(9-13)FCXXCXXXQ. The domain is found in HscB homologs from animals and
      plants as well as in magnetotactic bacteria. The metal-binding site of the domain
      is structurally similar to that of rubredoxin and several zinc finger proteins
      containing rubredoxin-like knuckles. The normal mode analysis of HscB revealed
      that this L-shaped protein preferentially undergoes a scissors-like motion that
      correlates well with the conformational changes of human HscB observed in the
      crystals.

PMID- 18713743
TI  - Small heat shock protein activity is regulated by variable oligomeric
      substructure.
AB  - The alpha-crystallins are members of the small heat shock protein family of
      molecular chaperones that have evolved to minimize intracellular protein
      aggregation; however, they are also implicated in a number of protein deposition
      diseases. In this study, we employed novel mass spectrometry techniques to
      investigate the changes in quaternary structure associated with this switch from
      chaperone to adjuvant of aggregation. We replicated the oligomeric rearrangements
      observed for post-translationally modified alpha-crystallins, without altering
      the protein sequence, by refolding the alpha-crystallins in vitro. This refolding
      resulted in a loss of dimeric substructure concomitant with an augmentation of
      substrate affinity. We show that packaging of small heat shock proteins into
      dimeric units is used to control the level of chaperone function by regulating
      the exposure of hydrophobic surfaces. We propose that a bias toward monomeric
      substructure is responsible for the aberrant chaperone behavior associated with
      the alpha-crystallins in protein deposition diseases.

PMID- 18713744
TI  - Ephrin-B2-induced cleavage of EphB2 receptor is mediated by matrix
      metalloproteinases to trigger cell repulsion.
AB  - EphB receptors provide crucial adhesive and repulsive signals during cell
      migration and axon guidance, but it is unclear how they switch between these
      opposing responses. Here we provide evidence of an important role for matrix
      metalloproteinases (MMPs) in repulsive EphB2 signaling. We found that EphB2 is
      cleaved by MMPs both in vitro and in vivo, and that this cleavage is induced by
      interaction with its ligand ephrin-B2. Our findings demonstrate that MMP-2/MMP-9
      specific inhibition or cleavage-resistant mutations in the ectodomain of EphB2
      can prevent EphB2-mediated cell-cell repulsion in HEK293 cells, and block ephrin
      B1-induced growth cone withdrawal in cultured hippocampal neurons. Transient
      expression of wtEphB2, but not noncleavable EphB2-4/5 mutant, restored ephrin-B1
      induced growth cone collapse and withdrawal in EphB-deficient neurons. The
      inhibition of EphB2 cleavage also had potent regulatory effects on EphB2
      activity. This study provides the first evidence that MMP-mediated cleavage of
      EphB2 is induced by receptor-ligand interactions at the cell surface and that
      this event triggers cell-repulsive responses.

PMID- 18713745
TI  - Ruffling of metalloporphyrins bound to IsdG and IsdI, two heme-degrading enzymes
      in Staphylococcus aureus.
AB  - IsdG and IsdI are paralogous proteins that are intracellular components of a
      complex heme uptake system in Staphylococcus aureus. IsdG and IsdI were shown
      previously to reductively degrade hemin. Crystal structures of the apoproteins
      show that these proteins belong to a newly identified heme degradation family
      distinct from canonical eukaryotic and prokaryotic heme oxygenases. Here we
      report the crystal structures of an inactive N7A variant of IsdG in complex with
      Fe(3+)-protoporphyrin IX (IsdG-hemin) and of IsdI in complex with cobalt
      protoporphyrin IX (IsdI-CoPPIX) to 1.8 A or better resolution. These structures
      show that the metalloporphyrins are buried into similar deep clefts such that the
      propionic acids form salt bridges to two Arg residues. His(77) (IsdG) or His(76)
      (IsdI), a critical residue required for activity, is coordinated to the Fe(3+) or
      Co(3+) atoms, respectively. The bound porphyrin rings form extensive steric
      interactions in the binding cleft such that the rings are highly distorted from
      the plane. This distortion is best described as ruffled and places the beta- and
      delta-meso carbons proximal to the distal oxygen-binding site. In the IsdG-hemin
      structure, Fe(3+) is pentacoordinate, and the distal side is occluded by the side
      chain of Ile(55). However, in the structure of IsdI-CoPPIX, the distal side of
      the CoPPIX accommodates a chloride ion in a cavity formed through a
      conformational change in Ile(55). The chloride ion participates in a hydrogen
      bond to the side chain amide of Asn(6). Together the structures suggest a
      reaction mechanism in which a reactive peroxide intermediate proceeds with
      nucleophilic oxidation at the beta- or delta-meso carbon of the hemin.

PMID- 18713746
TI  - Endogenous functions of the aryl hydrocarbon receptor (AHR): intersection of
      cytochrome P450 1 (CYP1)-metabolized eicosanoids and AHR biology.

PMID- 18713747
TI  - Ecto-nucleoside triphosphate diphosphohydrolase 1 (E-NTPDase1/CD39) regulates
      neutrophil chemotaxis by hydrolyzing released ATP to adenosine.
AB  - Polymorphonuclear neutrophils release ATP in response to stimulation by
      chemoattractants, such as the peptide N-formyl-methionyl-leucyl-phenylalanine.
      Released ATP and the hydrolytic product adenosine regulate chemotaxis of
      neutrophils by sequentially activating purinergic nucleotide and adenosine
      receptors, respectively. Here we show that that ecto-nucleoside triphosphate
      diphosphohydrolase 1 (E-NTPDase1, CD39) is a critical enzyme for hydrolysis of
      released ATP by neutrophils and for cell migration in response to multiple
      agonists (N-formyl-methionyl-leucyl-phenylalanine, interleukin-8, and C5a). Upon
      stimulation of human neutrophils or differentiated HL-60 cells in a chemotactic
      gradient, E-NTPDase1 tightly associates with the leading edge of polarized cells
      during chemotaxis. Inhibition of E-NTPDase1 reduces the migration speed of
      neutrophils but not their ability to detect the orientation of the gradient
      field. Studies of neutrophils from E-NTPDase1 knock-out mice reveal similar
      impairments of chemotaxis in vitro and in vivo. Thus, E-NTPDase1 plays an
      important role in regulating neutrophil chemotaxis by facilitating the hydrolysis
      of extracellular ATP.

PMID- 18713748
TI  - Protein kinase C-related kinase and ROCK are required for thrombin-induced
      endothelial cell permeability downstream from Galpha12/13 and Galpha11/q.
AB  - Increase in vascular permeability occurs under many physiological conditions such
      as wound repair, inflammation, and thrombotic reactions and is central in diverse
      human pathologies, including tumor-induced angiogenesis, ocular diseases, and
      septic shock. Thrombin is a pro-coagulant serine protease, which causes the local
      loss of endothelial barrier integrity thereby enabling the rapid extravasation of
      plasma proteins and the local formation of fibrin-containing clots. Available
      information suggests that thrombin induces endothelial permeability by promoting
      actomyosin contractility through the Rho/ROCK signaling pathway. Here we took
      advantage of pharmacological inhibitors, knockdown approaches, and the emerging
      knowledge on how permeability factors affect endothelial junctions to investigate
      in detail the mechanism underlying thrombin-induced endothelial permeability. We
      show that thrombin signals through PAR-1 and its coupled G proteins Galpha(12/13)
      and Galpha(11/q) to induce RhoA activation and intracellular calcium elevation,
      and that these events are interrelated. In turn, this leads to the stimulation of
      ROCK, which causes actin stress-fiber formation. However, this alone is not
      sufficient to account for thrombin-induced permeability. Instead, we found that
      protein kinase C-related kinase, a Rho-dependent serine/threonine kinase, is
      activated in endothelial cells upon thrombin stimulation and that its expression
      is required for endothelial permeability and the remodeling of cell-extracellular
      matrix and cell-cell adhesions. Our results demonstrate that the signal initiated
      by thrombin bifurcates at the level of RhoA to promote changes in the
      cytoskeletal architecture through ROCK, and the remodeling of focal adhesion
      components through protein kinase C-related kinase. Ultimately, both pathways
      converge to cause cell-cell junction disruption and provoke vascular leakage.

PMID- 18713749
TI  - P-selectin glycoprotein ligand-1 decameric repeats regulate selectin-dependent
      rolling under flow conditions.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1) interacts with selectins to support
      leukocyte rolling along vascular wall. L- and P-selectin bind to N-terminal
      tyrosine sulfate residues and to core-2 O-glycans attached to Thr-57, whereas
      tyrosine sulfation is not required for E-selectin binding. PSGL-1 extracellular
      domain contains decameric repeats, which extend L- and P-selectin binding sites
      far above the plasma membrane. We hypothesized that decamers may play a role in
      regulating PSGL-1 interactions with selectins. Chinese hamster ovary cells
      expressing wild-type PSGL-1 or PSGL-1 molecules exhibiting deletion or
      substitution of decamers with the tandem repeats of platelet glycoprotein Ibalpha
      were compared in their ability to roll on selectins and to bind soluble L- or P
      selectin. Deletion of decamers abrogated soluble L-selectin binding and cell
      rolling on L-selectin, whereas their substitution partially reversed these
      diminutions. P-selectin-dependent interactions with PSGL-1 were less affected by
      decamer deletion. Videomicroscopy analysis showed that decamers are required to
      stabilize L-selectin-dependent rolling. Importantly, adhesion assays performed on
      recombinant decamers demonstrated that they directly bind to E-selectin and
      promote slow rolling. Our results indicate that the role of decamers is to extend
      PSGL-1 N terminus far above the cell surface to support and stabilize leukocyte
      rolling on L- or P-selectin. In addition, they function as a cell adhesion
      receptor, which supports approximately 80% of E-selectin-dependent rolling.

PMID- 18713750
TI  - Potent inhibition and global co-localization implicate the transmembrane Kunitz
      type serine protease inhibitor hepatocyte growth factor activator inhibitor-2 in
      the regulation of epithelial matriptase activity.
AB  - Hepatocyte growth factor activator inhibitors (HAI)-1 and -2 are recently
      identified and closely related Kunitz-type transmembrane serine protease
      inhibitors. Whereas HAI-1 is well established as an inhibitor of the serine
      proteases matriptase and hepatocyte growth factor activator, the physiological
      targets of HAI-2 are unknown. Here we show that HAI-2 displays potent inhibitory
      activity toward matriptase, forms SDS-stable complexes with the serine protease,
      and blocks matriptase-dependent activation of its candidate physiological
      substrates proprostasin and cell surface-bound pro-urokinase plasminogen
      activator. To further explore the potential functional relationship between HAI-2
      and matriptase, we generated a transgenic mouse strain with a promoterless beta
      galactosidase marker gene inserted into the endogenous locus encoding HAI-2
      protein and performed a global high resolution mapping of the expression of HAI
      2, matriptase, and HAI-1 proteins in all adult tissues. This analysis showed
      striking co-localization of HAI-2 with matriptase and HAI-1 in epithelial cells
      of all major organ systems, thus strongly supporting a role of HAI-2 as a
      physiological regulator of matriptase activity, possibly acting in a redundant or
      partially redundant manner with HAI-1. Unlike HAI-1 and matriptase, however, HAI
      2 expression was also detected in non-epithelial cells of brain and lymph nodes,
      suggesting that HAI-2 may also be involved in inhibition of serine proteases
      other than matriptase.

PMID- 18713751
TI  - Alternative splicing of the guanylyl cyclase-A receptor modulates atrial
      natriuretic peptide signaling.
AB  - Atrial (ANP) and B-type natriuretic peptides (BNP) modulate blood pressure and
      volume through the stimulation of cyclic GMP production by their guanylyl cyclase
      A (GC-A) receptor. A novel isoform of GC-A has been identified that is the result
      of differential splicing of exon 4. The deletion of a 51-bp sequence is predicted
      to delete 17 amino acids (Lys314-Gln330) in the membrane-distal part of the
      extracellular domain. Reverse transcription-PCR analyses demonstrated low
      messenger RNA expression levels of spliced GC-A in all tissues. Homology modeling
      suggested that the alterations in the protein structure could interfere with ANP
      binding or signaling. Indeed, functional studies in transfected HEK 293 cells
      demonstrated that binding of ANP and ANP-induced cyclic GMP formation by GC
      ADelta(Lys314-Gln330) were totally abolished. Furthermore, cotransfection studies
      showed that this GC-A variant forms heterodimers with the wild type receptor and
      inhibits ligand-inducible cGMP generation. Finally, treatment of mice with
      angiotensin II (300 ng/kg/min during 7 days) resulted in enhanced pulmonary mRNA
      expression of spliced GC-A, which was concomitant to diminished GC-A/cGMP
      responses to ANP. We conclude that alternative splicing can regulate endogenous
      ANP/GC-A signaling. Angiotensin II-induced alternative splicing of GC-A may
      represent a novel mechanism for reducing the sensitivity to ANP.

PMID- 18713752
TI  - Self-assembly of Glut4 storage vesicles during differentiation of 3T3-L1
      adipocytes.
AB  - Glut4 storage vesicles (GSVs) represent translocation-competent vesicular
      carriers in fat and skeletal muscle cells that deliver Glut4 to the plasma
      membrane in response to insulin stimulation. GSVs include three major cargo
      proteins: Glut4, insulin-responsive aminopeptidase (IRAP), and sortilin. Previous
      work has suggested that the lumenal interaction between Glut4 and sortilin and
      the cytoplasmic interaction between sortilin and GGA adaptors play an important
      role in recruitment of Glut4 into the GSVs. However, the mechanism of IRAP
      targeting to this compartment remains unknown. To address this question, we show
      that in differentiating adipocytes IRAP enters the GSVs from the "donor"
      membranes on day 3 of differentiation. Forced expression of sortilin in
      undifferentiated cells does not recruit IRAP into the vesicles. However, double
      expression of sortilin and Glut4 reconstitutes functional GSVs that incorporate
      endogenous IRAP. To explain this process, we show by a yeast two-hybrid system
      and chemical cross-linking that the lumenal domain of IRAP can interact with the
      lumenal loop of Glut4. IRAP without the lumenal domain is faithfully targeted to
      the donor membranes but has significantly lower insulin responsiveness than full
      length IRAP. We suggest that lumenal interactions between Glut4 and IRAP play an
      important role in the assembly of the GSVs.

PMID- 18713753
TI  - Forchlorfenuron alters mammalian septin assembly, organization, and dynamics.
AB  - Septins are filamentous GTPases that associate with cell membranes and the
      cytoskeleton and play essential roles in cell division and cellular
      morphogenesis. Septins are implicated in many human diseases including cancer and
      neuropathies. Small molecules that reversibly perturb septin organization and
      function would be valuable tools for dissecting septin functions and could be
      used for therapeutic treatment of septin-related diseases. Forchlorfenuron (FCF)
      is a plant cytokinin previously shown to disrupt septin localization in budding
      yeast. However, it is unknown whether FCF directly targets septins and whether it
      affects septin organization and functions in mammalian cells. Here, we show that
      FCF alters septin assembly in vitro without affecting either actin or tubulin
      polymerization. In live mammalian cells, FCF dampens septin dynamics and induces
      the assembly of abnormally large septin structures. FCF has a low level of
      cytotoxicity, and these effects are reversed upon FCF washout. Significantly, FCF
      treatment induces mitotic and cell migration defects that phenocopy the effects
      of septin depletion by small interfering RNA. We conclude that FCF is a promising
      tool to study mammalian septin organization and functions.

PMID- 18713755
TI  - Reversal of peripheral and central neural storage and ataxia after recombinant
      enzyme replacement therapy in alpha-mannosidosis mice.
AB  - Despite the progress in the treatment of lysosomal storage disorders (LSDs)
      mainly by enzyme replacement therapy, only limited success was reported in
      targeting the appropriate lysosomal enzyme into the brain. This prevents
      efficient clearance of neuronal storage, which is present in many of these
      disorders including alpha-mannosidosis. Here we show that the neuropathology of a
      mouse model for alpha-mannosidosis can be efficiently treated using recombinant
      human alpha-mannosidase (rhLAMAN). After intravenous administration of different
      doses (25-500 U/kg), rhLAMAN was widely distributed among tissues, and
      immunohistochemistry revealed lysosomal delivery of the injected enzyme. Whereas
      low doses (25 U/kg) led to a significant clearance (<70%) in visceral tissues,
      higher doses were needed for a clear effect in central and peripheral nervous
      tissues. A distinct reduction (<50%) of brain storage required repeated high-dose
      injections (500 U/kg), whereas lower doses (250 U/kg) were sufficient for
      clearance of stored substrates in peripheral neurons of the trigeminal ganglion.
      Successful transfer across the blood-brain barrier was evident as the injected
      enzyme was found in hippocampal neurons, leading to a nearly complete
      disappearance of storage vacuoles. Importantly, the decrease in neuronal storage
      in the brain correlated with an improvement of the neuromotor disabilities found
      in untreated alpha-mannosidosis mice. Uptake of rhLAMAN seems to be independent
      of mannose-6-phosphate receptors, which is consistent with the low
      phosphorylation profile of the enzyme. These data suggest that high-dose
      injections of low phosphorylated enzymes might be an interesting option to
      efficiently treat LSDs with CNS involvement.

PMID- 18713754
TI  - A position effect on TRPS1 is associated with Ambras syndrome in humans and the
      Koala phenotype in mice.
AB  - Ambras syndrome (AS) is a rare form of congenital hypertrichosis with excessive
      hair on the shoulders, face and ears. Cytogenetic studies have previously
      implicated an association with rearrangements of chromosome 8. Here we define an
      11.5 Mb candidate interval for AS on chromosome 8q based on cytogenetic
      breakpoints in three patients. TRPS1, a gene within this interval, was deleted in
      a patient with an 8q23 chromosomal rearrangement, while its expression was
      significantly downregulated in another patient with an inversion breakpoint 7.3
      Mb downstream of TRPS1. Here, we describe the first potential long-range position
      effect on the expression of TRPS1. To gain insight into the mechanisms by which
      Trps1 affects the hair follicle, we performed a detailed analysis of the hair
      abnormalities in Koa mice, a mouse model of hypertrichosis. We found that the
      proximal breakpoint of the Koa inversion is located 791 kb upstream of Trps1.
      Quantitative real-time polymerase chain reaction, in situ hybridization and
      immunofluorescence analysis revealed that Trps1 expression levels are reduced in
      Koa mutant mice at the sites of pathology for the phenotype. We determined that
      the Koa inversion creates a new Sp1 binding site and translocates additional Sp1
      binding sites within a highly conserved stretch spanning the proximal breakpoint,
      providing a potential mechanism for the position effect. Collectively, these
      results describe a position effect that downregulates TRPS1 expression as the
      probable cause of hypertrichosis in AS in humans and the Koa phenotype in mice.

PMID- 18713757
TI  - Expression of p21waf1/Cip1 in stromal fibroblasts of primary breast tumors.
AB  - During carcinogenesis, stromal fibroblasts undergo certain changes in concert
      with their neoplastic neighbors, an interaction that progressively leads to a
      cancer-associated state. However, despite the increasing appreciation of the
      importance of stromal/tumor interactions in the progression of cancer, little is
      known about the factors responsible for regulating the crosstalk between stromal
      fibroblasts and neoplastic cells. Here we show that the stage of the disease in
      primary human breast lesions affects p21 expression in the fibroblasts. In
      stromal fibroblasts of benign fibroadenomas, p21 exhibits a periductal pattern of
      staining, which is abolished in malignant adenocarcinomas in which p21
      immunopositivity exhibits a mosaic pattern that eventually is abolished in more
      aggressive types of the disease. In order to address the role of fibroblasts' p21
      in tumorigenesis, we have reconstituted MCF7 human breast cancers in mice, with
      fibroblasts differing in the p21 status. These experiments showed that p21
      deficiency in stromal fibroblasts accelerates tumor growth through cell non
      autonomous mechanism(s). In addition, even a transient, siRNA-mediated p21
      suppression in fibroblasts sufficiently stimulates MCF7 and MDA-MB-231 growth in
      vivo. We propose that p21 regulation is intimately linked with the ability of
      stromal cells to affect tumor growth.

PMID- 18713756
TI  - Association of the tumour necrosis factor-308 variant with differential response
      to anti-TNF agents in the treatment of rheumatoid arthritis.
AB  - Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of
      patients with rheumatoid arthritis (RA). These therapies are, however, expensive
      and 30% of patients fail to respond. In a large cohort of Caucasian RA patients
      treated with anti-TNF medications (total n = 1050, etanercept n = 455, infliximab
      n = 450), we investigated whether genotypes of eight single nucleotide
      polymorphisms in the region containing the TNF gene were associated with response
      to anti-TNF therapy. Linear regression analyses adjusted for baseline 28 joint
      disease activity score (DAS28), baseline health assessment questionnaire score,
      gender and concurrent disease modifying anti-rheumatic drug treatment were used
      to assess association of these polymorphisms with treatment response, defined by
      change in DAS28 after 6 months. Analyses were performed in the entire cohort, and
      also stratified by anti-TNF agent. Association between DAS28 response and TNF-308
      (rs1800629) genotype (P = 0.001) was detected across the whole cohort. After
      stratification by anti-TNF agent, the rare TNF-308AA genotype was associated with
      a significantly poorer response compared with TNF-308GG in etanercept (P = 0.001,
      n = 7) but not infliximab (P = 0.8, n = 17) treated patients. Conversely, the GA
      genotype at TNF-238 (rs361525) was associated with a poorer response to
      infliximab (P = 0.028, n = 40), but not etanercept (P = 0.6, n = 33). Owing to
      the small numbers of patients in some of the genotype groups examined, our data
      must be regarded as preliminary and will require replication in further large
      cohorts of anti-TNF-treated patients. If confirmed, our findings suggest the
      potential for genotype at these markers to aid selection of anti-TNF agent in
      patients with RA.

PMID- 18713758
TI  - Influence of DDD rate response pacing with integrated double sensors on physical
      efficiency and quality of life.
AB  - AIMS: The aim of this study was to evaluate whether the use of a double sensor
      gives additional benefits for patients in improving physical efficiency as well
      as quality of life (QoL) as compared to the accelerometer sensor alone. METHODS
      AND RESULTS: The presented research is a prospective, randomized, single-blind
      clinical trial. Double-sensor (accelerometer and minute-ventilation) pacemakers
      (Guidant, Pulsar Max DR) were implanted in 20 patients with sinus node
      dysfunction (SND) and chronotropic incompetence. After randomization, patients
      were placed in one of two groups: 1, only the accelerometer sensor was activated;
      2, both sensors were activated. After a 3-month follow-up, an initial cardio
      pulmonary exercise test was performed, after which the patients were placed in
      the opposite group for a further 3 months. Finally, the second tests were
      performed. In 75% of the patients an improvement in QoL was observed in the
      double-sensor group (P = 0.0242) when compared with the single-sensor group. The
      addition of a ventilating sensor had no influence on the duration of exercise
      test (A: 11 +/- 3.19 vs. B: 11 +/- 2.92 P = 1.0000). The parameters of cardio
      pulmonary exercise tests recorded in situations A and B before exertion, and 6
      minutes after exertion were not statistically different. CONCLUSION: The use of
      double-sensor pacemakers does not improve physical efficiency; however, it does
      improve QoL.

PMID- 18713759
TI  - Improving clinical outcomes by reducing bleeding in patients with non-ST
      elevation acute coronary syndromes.
AB  - AIMS: Bleeding in patients with coronary artery disease has been linked with
      adverse outcomes. We examined the incidence and outcomes after bleeding in 20 078
      patients with acute coronary syndromes (ACS) enrolled in the OASIS-5 trial who
      were treated with fondaparinux or the low-molecular weight heparin, enoxaparin.
      METHODS AND RESULTS: Nine hundred and ninety (4.9%) patients developed major
      bleeding and 423 (2.1%) developed minor bleeding. Fondaparinux compared with
      enoxaparin reduced fatal bleeding [0.07 vs. 0.22%, relative risk (RR) 0.30, 95%
      CI: 0.13-0.71], non-fatal major bleeding (2.2 vs. 4.2%, RR 0.52, 95% CI: 0.44
      0.61), minor bleeding (1.1 vs. 3.2%, RR 0.34, 95% CI: 0.27-0.42), and need for
      transfusion (1.8 vs. 3.1%, RR 0.56, 95% CI: 0.47-0.61) during the first 9 days.
      One of every six deaths during the first 30 days occurred in patients who
      experienced bleeding. Cox proportional hazards model revealed that major bleeding
      was associated with about a four-fold increased hazard of death, myocardial
      infarction, or stroke during the first 30 days and about a three-fold increased
      hazard during 180 days of follow up. CONCLUSION: Bleeding in patients with ACS is
      a powerful determinant of fatal and non-fatal outcomes. Reducing the risk of
      bleeding using a safer anticoagulant strategy during the first 9 days is
      associated with substantial reductions in morbidity and mortality.

PMID- 18713760
TI  - Pharmacokinetics and pharmacodynamics of drug interactions involving rifampicin,
      rifabutin and antimalarial drugs.
AB  - Malaria and tuberculosis (TB) are two major global diseases mostly affecting the
      developing countries. Their treatment is often complex because of the drugs used,
      multidrug resistance, drug interactions and logistic problems such as drug
      availability and access. Patients are treated for TB for a minimum of 6 months
      and may concomitantly develop and be treated for malaria, especially during the
      rainy season. Rifampicin, a standard component of combination regimens for
      treating TB, is a potent inducer of hepatic cytochrome and other metabolic
      enzymes and is able to influence the pharmacokinetics of many drugs. Rifabutin,
      another rifamycin used less frequently than rifampicin, can also interact with
      drugs metabolized through the hepatic cytochromes. The mechanisms of any
      interaction of rifamycins with drugs used in malaria are not well defined. To
      complicate matters, acute malaria also plays a role in the pharmacokinetics and
      pharmacodynamics of drugs (i.e. quinine). The aim of this paper is to review
      known and potential drug-drug interactions between rifampicin, rifabutin and
      antimalarial drugs.

PMID- 18713761
TI  - Prophylactic mirtazapine reduces intrathecal morphine-induced pruritus.
AB  - BACKGROUND: Activation of the serotonergic system is an important factor in the
      pathogenesis of intrathecal morphine-induced pruritus. Mirtazapine is a new
      antidepressant that selectively blocks 5-HT(2) and 5-HT(3) receptors. We
      therefore tested the hypothesis that preoperative mirtazapine would reduce the
      incidence of intrathecal morphine-induced pruritus. METHODS: One hundred and ten
      ASA I patients undergoing lower limb surgery under spinal anaesthesia were
      randomly allocated into two equal groups and received either mirtazapine 30 mg or
      an orally disintegrating placebo tablet 1 h before operation in a prospective,
      double-blinded trial. All patients received an intrathecal injection of 15 mg of
      0.5% isobaric bupivacaine and 0.2 mg preservative-free morphine. The occurrence
      and the severity of pruritus were assessed at 3, 6, 9, 12, and 24 h after
      intrathecal morphine. RESULTS: Pruritus was significantly more frequent in the
      placebo group compared with the mirtazapine group (75% vs 52%, respectively;
      P=0.0245). The time to onset of pruritus in the two groups was also significantly
      different. The patients who experienced pruritus in the placebo group had a
      faster onset time than that in the mirtazapine group [mean (sd): 3.2 (0.8) vs 7.2
      (4.1) h, P<0.0001]. CONCLUSIONS: Mirtazapine premedication prevents pruritus
      induced by intrathecal morphine in patients undergoing lower limb surgery with
      spinal anaesthesia.

PMID- 18713762
TI  - Influence of resident training on anaesthesia induction times.
AB  - BACKGROUND: The effect of resident training in anaesthesiology on operating room
      (OR) economics is an issue of debate. Comparisons of anaesthesia process times
      between residents and consultants might be systematically skewed by interactions
      of anaesthesia technique and patient factors. METHODS: In this prospective,
      observational study, we analysed anaesthesia process times in 599 cases performed
      for four different surgical services in a University hospital. The following
      factors were recorded for each case and used in multivariate analyses of process
      times: age, American Society of Anesthesiologist (ASA) status, BMI, emergency
      status, the educational level of the anaesthetist, and the anaesthesia technique.
      RESULTS: In the non-adjusted comparison, only for two of seven anaesthetic
      techniques did resident cases have statistically significant longer induction
      times than consultant cases: general anaesthesia with placement of a central
      venous catheter [mean (sd) anaesthesia time for resident cases 38.2 (17.0) vs
      22.3 (10.0) min for consultant cases, P=0.001] and general anaesthesia with a
      laryngeal mask airway [resident cases 11.3 (5.5) vs consultant cases 7.3 (5.0)
      min, P=0.003]. Anaesthetic technique had the greatest effect on anaesthesia
      induction time. Educational level of the anaesthetist and age of the patients had
      small, but significant effects. CONCLUSIONS: Anaesthesia cases performed by
      residents have in some, but not in all, anaesthesia techniques increased process
      times compared with cases performed by consultants. This limits a possible
      negative impact on OR economics by resident education. Patient-based factors
      including ASA status, BMI, and emergency status have minimal or no effect on
      anaesthesia process times.

PMID- 18713763
TI  - Biochemical mechanism on GABA accumulation during fruit development in tomato.
AB  - A large amount of gamma-aminobutyric acid (GABA) was found to accumulate in
      tomato (Solanum lycopersicum) fruits before the breaker stage. Shortly
      thereafter, GABA was rapidly catabolized after the breaker stage. We screened the
      GABA-rich tomato cultivar 'DG03-9' which did not show rapid GABA catabolism after
      the breaker stage. Although GABA hyperaccumulation and rapid catabolism in fruits
      is well known, the mechanisms are not clearly understood. In order to clarify
      these mechanisms, we performed comparative studies of 'Micro-Tom' and 'DG03-9'
      fruits for the analysis of gene expression levels, protein levels and enzymatic
      activity levels of GABA biosynthesis- and catabolism-related enzymes. During GABA
      accumulation, we found positive correlations among GABA contents and expression
      levels of SlGAD2 and SlGAD3. Both of these genes encode glutamate decarboxylase
      (GAD) which is a key enzyme of GABA biosynthesis. During GABA catabolism, we
      found a strong correlation between GABA contents and enzyme activity of alpha
      ketoglutarate-dependent GABA transaminase (GABA-TK). The contents of glutamate
      and aspartate, which are synthesized from GABA and glutamate, respectively,
      increased with elevation of GABA-TK enzymatic activity. GABA-TK is the major GABA
      transaminase form in animals and appears to be a minor form in plants. In 'DG03
      9' fruits, GAD enzymatic activity was prolonged until the ripening stage, and
      GABA-TK activity was significantly low. Taken together, our results suggest that
      GAD and GABA-TK play crucial roles in GABA accumulation and catabolism,
      respectively, in tomato fruits.

PMID- 18713764
TI  - Measuring arsenic exposure, metabolism, and biological effects: the role of urine
      proteomics.

PMID- 18713765
TI  - Higher levels of ethyl paraben and butyl paraben in rat amniotic fluid than in
      maternal plasma after subcutaneous administration.
AB  - Parabens are a group of antimicrobial preservatives widely used in cosmetics,
      pharmaceuticals, and in foods. Previous in vitro and in vivo studies have shown
      weak estrogenic effects of some parabens. Thus, especially, exposure of fetus and
      infants via the mother is a matter of concern. In order to obtain more knowledge
      about the distribution of ethyl paraben and butyl paraben in pregnant rats and
      pups after perinatal exposure, the presented study was designed. The data show
      response and distribution of ethyl paraben and butyl paraben in maternal rat
      plasma, pools of amniotic fluids, placenta, whole-body fetuses, and in fetal
      liver after dosing of dams with 100, 200, and 400 mg/kg body weight (bw)/day from
      gestational day 7 to 21. After cesarean section of dams, the fluids and tissues
      were collected, deconjugated, and purified by solid-phase extraction, and ethyl
      paraben and butyl paraben were analyzed by liquid chromatography-tandem mass
      spectrometry. Markedly higher levels of ethyl paraben compared to butyl paraben
      were found in all fluids and tissues. Both ethyl paraben and butyl paraben in
      maternal plasma, livers, and whole-body tissues from fetus seemed to be saturated
      after dosing with >or= 100 mg/kg bw/day, while both compounds were excreted into
      amniotic fluid in a dose-dependent manner. Significant difference was found
      between the level of ethyl paraben in maternal plasma and amniotic fluid after
      dosing with 200 mg/kg bw/day as well as between the levels of butyl paraben in
      maternal plasma and amniotic fluid after dosing with 100, 200, and 400 mg/kg
      bw/day.

PMID- 18713766
TI  - Activation of mouse and human peroxisome proliferator-activated receptor alpha by
      perfluoroalkyl acids of different functional groups and chain lengths.
AB  - Perfluoroalkyl acids (PFAAs) are surfactants used in consumer products and
      persist in the environment. Some PFAAs elicit adverse effects on rodent
      development and survival. PFAAs can activate peroxisome proliferator-activated
      receptor alpha (PPARalpha) and may act via PPARalpha to produce some of their
      effects. This study evaluated the ability of numerous PFAAs to induce mouse and
      human PPARalpha activity in a transiently transfected COS-1 cell assay. COS-1
      cells were transfected with either a mouse or human PPARalpha receptor-luciferase
      reporter plasmid. After 24 h, cells were exposed to either negative controls
      (water or dimethyl sulfoxide, 0.1%); positive control (WY-14643, PPARalpha
      agonist); perfluorooctanoic acid or perfluorononanoic acid at 0.5-100 microM;
      perfluorobutanoic acid, perfluorohexanoic acid, perfluorohexane sulfonate, or
      perfluorodecanoic acid (PFDA) at 5-100 microM; or perfluorobutane sulfonate or
      perfluorooctane sulfonate at 1-250 microM. After 24 h of exposure, luciferase
      activity from the plasmid was measured. Each PFAA activated both mouse and human
      PPARalpha in a concentration-dependent fashion, except PFDA with human PPARalpha.
      Activation of PPARalpha by PFAA carboxylates was positively correlated with
      carbon chain length, up to C9. PPARalpha activity was higher in response to
      carboxylates compared to sulfonates. Activation of mouse PPARalpha was generally
      higher compared to that of human PPARalpha. We conclude that, in general, (1)
      PFAAs of increasing carbon backbone chain lengths induce increasing activity of
      the mouse and human PPARalpha with a few exceptions, (2) PFAA carboxylates are
      stronger activators of mouse and human PPARalpha than PFAA sulfonates, and (3) in
      most cases, the mouse PPARalpha appears to be more sensitive to PFAAs than the
      human PPARalpha in this model.

PMID- 18713767
TI  - Predictors of shoulder pain and shoulder disability after one year in diabetic
      outpatients.
AB  - OBJECTIVE: To investigate factors associated with changes in shoulder pain and
      disability in diabetic outpatients over 1 yr. METHODS: Cross-sectional study with
      12-month follow-up in diabetic outpatients (n = 179) using the shoulder pain and
      disability index (SPADI) and SF-36 version 2. RESULTS: Patients with diabetes and
      shoulder pain or disability are more likely to be older and female. After 12
      months of follow-up, one-quarter of participants without pre-existing symptoms at
      baseline developed clinically significant pain (28%) or disability (25%). Of the
      patients with pre-existing shoulder pain or disability, half reported clinically
      significant worsening (10 percentage points) in shoulder pain (58%) or disability
      (45%) over 12 months. Few patients demonstrated clinically significant
      improvement in pain (11%) or disability scores (19%). The remaining one-third of
      the patients reported no change in symptoms (30% pain; 35% disability).
      Increasing intensity of pain scores between baseline and 12 months was associated
      with older age, higher HbA(1c) and less pain at baseline. Increasing disability
      score between baseline and 12 months was associated with having had eye laser
      surgery, greater pain at baseline and less disability at baseline. CONCLUSION:
      Shoulder pain and disability are common, and persistent in adults with diabetes.
      Having higher HbA(1c) levels or having had treatment for retinopathy was
      associated with worsening shoulder pain and disability, confirming that glycaemic
      control and diabetic complications are associated with worsening shoulder pain or
      disability over 12 months of observation.

PMID- 18713769
TI  - 'I just thought it was normal aches and pains': a qualitative study of decision
      making processes in patients with early rheumatoid arthritis.
AB  - OBJECTIVE: Effective treatment can only be given during the early stages of RA if
      patients are seen early. However, many patients delay for prolonged periods
      before seeking medical advice. This study explores factors influencing the
      decision to seek medical advice in RA patients. METHODS: In-depth, semi
      structured interviews were carried out with 24 patients. Purposive sampling
      ensured a cross-section in terms of time to presentation, gender, age and ethnic
      background. Interview transcripts were analysed and themes identified using
      established methods. RESULTS: Four main themes influenced the decision to seek
      medical advice: (i) symptom experience: the severity of symptoms and their impact
      on functional ability; (ii) symptom evaluation: the patient's explanation for
      their symptoms and recognition of their significance; (iii) knowledge of RA and
      available therapies; and (iv) experience of and attitudes towards health care
      providers. A significant and rapid impact of the disease on functional ability
      characterized those presenting early. Many developed an explanation for their
      symptoms that related to preceding activities. Recognition that this explanation
      was inadequate to explain symptom progression frequently prompted a consultation.
      Only one patient sought advice because she thought that she might have RA.
      CONCLUSIONS: Symptom evaluation is a key factor influencing how quickly medical
      advice is sought in other diseases. In contrast to the situation with many
      cancers where there is widespread association of symptoms and signs with the
      eventual diagnosis, this was not the case in RA. Our findings should inform
      strategies to reduce delays in help-seeking in people with early RA.

PMID- 18713770
TI  - Comment on: NICE guidance does not tally with clinical practice--a district
      general experience.

PMID- 18713771
TI  - Influence of inherited and acquired thrombophilic defects on the clinical
      manifestations of mixed cryoglobulinaemia.
AB  - OBJECTIVE: To investigate the contribution of inherited and acquired
      thrombophilic defects to the clinical manifestations of mixed cryoglobulinaemia
      vasculitis. METHODS: The following thrombophilic defects were investigated in 64
      consecutive patients with HCV-associated mixed cryoglobulinaemia: aPLs, lupus
      anti-coagulant, homocysteinaemia, protein C and protein S concentrations,
      activated protein C resistance, plasminogen activator inhibitor-1 4G4G and 5G5G
      genotypes, and the presence of mutations of factor V (Leiden and H1299R), of
      prothrombin (G20210A) and of methyl tetrahydrofolate reductase (C677T and
      A1298C). Additional variables were demographic data, duration of the disease,
      cryocrit level and vascular risk factors (diabetes, hypertension,
      hypercholesterolaemia and smoking habit). The following clinical manifestations
      of mixed cryoglobulinaemia were analysed as dependent covariates: severity of
      purpura, presence of necrotic skin ulcers, presence of peripheral neuropathy and
      presence of kidney disease. RESULTS: Logistic regression analysis identified
      hyperhomocysteinaemia as a risk factor for severe purpura (P < 0.0001) and for
      the presence of skin ulcers (P < 0.0001), whereas none of the other thrombophilic
      defects influenced the clinical presentation of mixed cryoglobulinaemia. Purpura
      improved in two patients after lowering homocysteine with vitamin
      supplementation. CONCLUSIONS: Hyperhomocysteinaemia may be a risk factor for
      severe cutaneous manifestations in mixed cryoglobulinaemia.

PMID- 18713777
TI  - Hypertrophic cardiomyopathy and athlete's heart: a tale of two entities.
AB  - Sudden death during sports activities, although unfrequent, is a tragic event
      with great impact on both the general and medical communities. The two commonest
      conditions leading to sudden cardiac death in young athletes are hyperthrophic
      cardiomyopathy (HCM), the main cause in the USA, and arrythmogenic right
      ventricular cardiomyopathy, which is the leading cause in Europe. We report the
      case of a 17-year-old football player with a pathological electrocardiography
      (ECG) in the pre-participation screening programme, highly suggestive of HCM, in
      which ECG study showed a septum thickness of 28 mm. Genetic analysis revealed R
      495 W mutation in the 18 exon of the MyBPC3 (myosin-binding protein C) and sports
      activities were contraindicated. Two years later, septum thickness was 19.5 mm.
      Usefulness of 12-lead ECG, differential diagnosis between athlete's heart and
      HCM, and the stratification in patients with HCM are discussed.

PMID- 18713778
TI  - Occult injury in the residual lung after pneumonectomy in mice.
AB  - OBJECTIVES: We aimed to determine the acute phase impact of pneumonectomy with
      respect to injury in the remaining lung using a murine model, and to investigate
      the profiles of inflammatory mediators including high mobility group box 1
      protein (HMGB1) following surgery and administration of low dose intratracheal
      lipopolysaccharide. METHODS: Mice received left pneumonectomy with intratracheal
      administration of either saline or lipopolysaccharide. Lung permeability index,
      lung wet-to-dry weight ratio, pathological findings, HMGB1 levels in
      bronchoalveolar lavage fluid (BALF) and plasma, and cytokine profiles in BALF
      were assessed 24 h after surgery. RESULTS: Index of capillary permeability, lung
      water content, and neutrophil and macrophage counts in BALF were significantly
      increased by pneumonectomy. These parameters were highest in the mice with
      pneumonectomy with intratracheal administration of lipopolysaccharide. On lung
      pathology, neutrophil infiltration was prominent in the residual lung after
      pneumonectomy. HMGB1 levels were significantly higher in both BALF and plasma in
      the mice with pneumonectomy, and were highest in those with pneumonectomy and
      intratracheal administration of lipopolysaccharide. Pro-inflammatory cytokine
      levels including interferon-gamma significantly increased in BALF in the mice
      with pneumonectomy. CONCLUSIONS: It was suggested that pneumonectomy itself may
      cause occult lung injury in the acute phase (24 h) of post-surgery which could be
      enhanced by inflammatory stimulus, such as bacterial component, leading to
      significant lung injury. HMGB1 might be involved in the pathogenesis of the
      occult lung injury.

PMID- 18713779
TI  - Preassembled stentless valved-conduit for the replacement of the ascending aorta
      and aortic root.
AB  - Here we report the early clinical results of a new preassembled stentless valved
      conduit incorporating artificial sinuses of Valsalva (BioValsalva). This new
      composite conduit incorporates a stentless porcine aortic valve (Elan, Vascutek
      Terumo, UK) suspended within a triple-layered vascular conduit (Triplex, Vascutek
      Terumo, UK) constructed with sinuses of Valsalva. Between December 2006 and
      January 2008, 17 patients with the mean age of 65 years underwent aortic valve,
      root and ascending aorta replacement with the BioValsalva valved-conduit. There
      was no perioperative mortality. There were no myocardial infarctions, cardiac
      failure or cerebrovascular events. Mean cardiopulmonary bypass time was 156+/-56
      min and ischemic time was 112+/-33 min. Eight patients required deep hypothermic
      circulatory arrest for additional distal ascending aorta replacement. Mean
      mediastinal drainage was 499+/-262 ml. Postoperative transthoracic
      echocardiography and CT-scans of the aorta in all patients before discharge
      demonstrated well-functioning prosthetic aortic valves with small residual mean
      gradients, no regurgitation, and the presence of sinuses of Valsalva. In
      conclusion, the novel prefabricated, composite stentless valved-conduit
      BioValsalva possesses excellent hemodynamic performance and can be implanted with
      low morbidity. In addition, the conduit material has good hemostatic properties
      which reduced bleeding, and is easy to implant with a variety of surgical
      techniques.

PMID- 18713780
TI  - Huge thymoma: role of preoperative WHO histological classification.
AB  - A 57-year-old woman was admitted to our hospital with complaints of recent onset
      of dyspnea on exertion. A chest computed tomography revealed a large mediastinal
      mass which extrinsically compressed the heart and mediastinal structures,
      occupying one half of the hemithorax. A needle biopsy was performed to find a
      thymoma with type AB according to the WHO classification. Based on the
      radiological and histological finding a surgery for the tumor was achieved by
      exploratory VATS thoracotomy followed by thymectomy through a median sternotomy
      with tumor extirpation of 910 g in weight. A definite diagnosis of thymoma
      (Masaoka I) without capsular invasion was obtained from the pathologic findings,
      including positive immunohistochemical staining for CD1a and cytokeratin.

PMID- 18713781
TI  - Correlation of passivity symptoms and dysfunctional visuomotor action monitoring
      in psychosis.
AB  - Passivity experiences are hallmark symptoms of schizophrenia that can be
      characterized by the belief that one's thoughts or actions are controlled by an
      external agent. It has recently been suggested that these psychotic experiences
      result from defective monitoring of one's own actions, i.e. disturbed comparison
      of actions and perceived outcomes. In this study, we examined the function of the
      previously characterized action monitoring network of the inferior parietal
      lobule (IPL), medial (mPFC) and lateral prefrontal cortices in patients with
      different levels of passivity symptoms with an fMRI task. The visuomotor fMRI
      task demanded control of visually perceived object movements by alternating
      button presses with the left and the right index finger. In the monitoring
      condition of this task subjects stopped their actions whenever they detected
      visuomotor incongruence. fMRI and behavioural data from 15 patients were tested
      for correlation with passivity symptoms using standardized Scale for Assessment
      of Positive Symptoms (SAPS)- and AMDP- passivity symptom ratings. Both types of
      data were tested for differences between the patients group and 15 healthy
      controls. In the patient group we found the expected correlation of passivity
      symptoms and visuomotor monitoring performance. There was a significant positive
      correlation of passivity symptoms with increased latency of incongruence
      detection and a negative correlation of SAPS-passivity with the number of
      detected events. fMRI data revealed correlations of passivity symptoms with
      activation in bilateral IPL, primary motor and sensory cortices in the action
      monitoring condition. A correlation of passivity symptoms with the main
      experimental effect (actions with -- actions without monitoring) was found in the
      posterior cingulate cortex (PCC) and in the left IPL. No group differences or
      group by task interactions were found within the visuomotor-action-monitoring
      network. Our results demonstrate the association between passivity symptoms and
      the dysfunction of visuomotor action monitoring and support the idea that
      psychotic passivity experiences result from dysfunctions of central action
      monitoring mechanisms: According to pre-existing concepts of parietal cortex
      function, IPL-hyperactivation may represent an increase in false detections of
      visuomotor incongruence while the correlation between passivity and the
      differential effect of monitoring on PCC-activation assumedly represents greater
      self-monitoring effort in passivity experiences.

PMID- 18713782
TI  - Personal radiation doses in PET/CT facility: measurements vs. calculations.
AB  - The estimation of shielding requirement of a new positron emission tomography
      (PET) facility is essential. Because of penetrating annihilation photons, not
      only radiation safety in the vicinity of patients should be considered, but also
      rooms adjacent to uptake and imaging rooms should be taken into account. Before
      installing a PET/CT camera to nuclear medicine facilities of Helsinki University
      Central Hospital (HUCH), a typical PET imaging day was simulated using phantoms.
      Phantoms were filled with 300 +/- 36 MBq of (18)F isotope and dose rates were
      measured at 12 central locations in the laboratory. In addition to measurements,
      dose rates were also calculated using guidelines of AAPM Task Group 108. The
      relationship between the measured and calculated dose rates was found to be good
      and statistically significant, using Pearson's correlation test. The evaluated
      monthly doses were compared with personal dosemeter readings. AAPM's report gives
      practical tools for evaluation of radiation shielding. Calculations can be
      carried out successfully for existing hospital complexes too. However,
      calculations should be carried out carefully, because especially doors, windows
      and partitions can easily cause underestimation of shielding requirements as
      shown in this work.

PMID- 18713783
TI  - Deoxyspergualin in relapsing and refractory Wegener's granulomatosis.
AB  - OBJECTIVES: Conventional therapy of Wegener's granulomatosis with
      cyclophosphamide and corticosteroids is limited by incomplete remissions and a
      high relapse rate. The efficacy and safety of an alternative immunosuppressive
      drug, deoxyspergualin, was evaluated in patients with relapsing or refractory
      disease. METHODS: A prospective, international, multicentre, single-limb, open
      label study. Entry required active Wegener's granulomatosis with a Birmingham
      vasculitis activity score (BVAS) > or =4 and previous therapy with
      cyclophosphamide or methotrexate. Immunosuppressive drugs were withdrawn at entry
      and prednisolone doses adjusted according to clinical status. Deoxyspergualin,
      0.5 mg/kg per day, was self-administered by subcutaneous injection in six cycles
      of 21 days with a 7-day washout between cycles. Cycles were stopped early for
      white blood count less than 4000 cells/mm(3). The primary endpoint was complete
      remission (BVAS 0 for at least 2 months) or partial remission (BVAS <50% of entry
      score). After the sixth cycle azathioprine was commenced and follow-up continued
      for 6 months. RESULTS: 42/44 patients (95%) achieved at least partial remission
      and 20/44 (45%) achieved complete remission. BVAS fell from 12 (4-25), median
      (range) at baseline to 2 (0-14) at the end of the study (p<0.001). Prednisolone
      doses were reduced from 20 to 8 mg/day (p<0.001). Relapses occurred in 18 (43%)
      patients after a median of 170 (44-316) days after achieving remission. Severe or
      life-threatening (> or = grade 3) treatment-related adverse events occurred in 24
      (53%) patients mostly due to leucopaenias. CONCLUSIONS: Deoxyspergualin achieved
      a high rate of disease remission and permitted prednisolone reduction in
      refractory or relapsing Wegener's granulomatosis. Adverse events were common but
      rarely led to treatment discontinuation.

PMID- 18713784
TI  - Effects of infliximab therapy on biological markers of synovium activity and
      cartilage breakdown in patients with rheumatoid arthritis.
AB  - BACKGROUND: Defining the remission criteria of rheumatoid arthritis (RA) remains
      a critical issue. Markers of synovium activity, urinary glucosyl-galactosyl
      pyridinoline (Glc-Gal-PYD) and of cartilage destruction, urinary C-terminal
      crosslinking telopeptide of type II collagen (CTX-II) have been shown to reflect
      disease activity and joint damage progression in RA. METHODS: The prospective
      study cohort comprised 66 RA patients treated with infliximab and methotrexate
      and 76 healthy controls. Measurements of urinary Glc-Gal-PYD and CTX-II were
      performed at baseline and at 1 year of infliximab therapy. RESULTS: At baseline,
      urinary Glc-Gal-PYD and CTX-II levels were increased in patients with RA and
      correlated with modified Sharp scores and progression of joint damage. Patients
      with more progressive joint destruction had higher Glc-Gly-PYD and CTX-II
      baseline levels. CONCLUSION: These markers reflected bone erosion evolution and
      might be useful for treatment monitoring and evaluation of RA. Markers remained
      high even in clinical responders after infliximab, suggesting persistence of
      synovitis.

PMID- 18713785
TI  - Estimating the prevalence of polymyositis and dermatomyositis from administrative
      data: age, sex and regional differences.
AB  - OBJECTIVE: To estimate the prevalence of polymyositis and dermatomyositis using
      population-based administrative data, the sensitivity of case ascertainment
      approaches and patient demographics and these parameters. METHODS: Cases were
      ascertained from Quebec physician billing and hospitalisation databases
      (approximately 7.5 million beneficiaries). Three different case definition
      algorithms were compared, and statistical methods were also used that account for
      imperfect case ascertainment, to generate estimates of disease prevalence and
      case ascertainment sensitivity. A hierarchical Bayesian latent class regression
      model was developed to assess patient characteristics with respect to these
      parameter estimates. RESULTS: Using methods that account for the imperfect nature
      of both billing and hospitalisation databases, the 2003 prevalence of
      polymyositis and dermatomyositis was estimated to be 21.5/100,000 (95% credible
      interval (CrI) 19.4 to 23.9). Prevalence was higher for women and for older
      individuals, with a tendency for higher prevalence in urban areas. Prevalence
      estimates were lowest in young rural men (2.7/100,000, 95% CrI 1.6 to 4.1) and
      highest in older urban women (70/100,000, 95% CrI 61.3 to 79.3). Sensitivity of
      case ascertainment tended to be lower for older versus younger individuals,
      particularly for rheumatology billing data. Billing data appeared more sensitive
      in ascertaining cases in urban (vs rural) regions, whereas hospitalisation data
      seemed most useful in rural areas. CONCLUSIONS: Marked variations were found in
      the prevalence of polymyositis and dermatomyositis according to age, sex and
      region. These methods allow adjustment for the imperfect nature of multiple data
      sources and estimation of the sensitivity of different case ascertainment
      approaches.

PMID- 18713786
TI  - Quantitative assessment of antibodies to ribonucleoproteins in primary Sjogren
      syndrome: correlation with B-cell biomarkers and disease activity.
AB  - OBJECTIVES: To assess the added value of using a radioligand assay (RLA) compared
      with ELISA to detect antibodies to SSA, SSB and RNP, and to analyse the
      correlation between autoantibody levels, B-cell biomarkers and disease activity.
      PATIENTS AND METHODS: Antibodies to SSA, SSB and RNP were assessed in 127
      patients with primary Sjogren syndrome (pSS) using an RLA and ELISA. In parallel,
      measures of B-cell activation were determined including serum levels of B-cell
      activating factor of the tumour necrosis factor family or BLyS (BAFF). RESULTS:
      RLA was more sensitive than ELISA for the detection of antibodies to SSB (54% of
      positive samples versus 37%, respectively) and antibodies to RNP (9% vs 3%). No
      difference was seen for the sensitivity of detection of antibodies to SSA. Anti
      SSA and anti-SSB levels were correlated with both techniques. Mean levels of
      antibodies to SSA were significantly higher in patients presenting antibodies to
      both SSA and SSB than in those exhibiting antibodies to SSA only (RLA: mean (SEM)
      anti-SSA levels 2343 (158) cpm vs 1348 (286) cpm, respectively, p = 0.02; ELISA:
      6.8 (0.8) vs 3.8 (0.4), respectively, p = 0.003). Levels of antibodies to SSA and
      SSB significantly correlated with those of circulating BAFF (r = 0.4, p = 0.004
      and r = 0.6, p<0.001, respectively) and with B-cell biomarkers, including levels
      of gammaglobulins, beta(2) microglobulin and rheumatoid factor. CONCLUSION: RLA
      allowed a quantitative and more sensitive detection of antibodies to SSB and RNP
      in pSS. Quantitative assessment of autoantibodies might disclose a biomarker of
      disease activity and enable further insight into the pathogenesis of the
      spreading of the autoantibody response.

PMID- 18713787
TI  - The interleukin 23 receptor gene does not confer risk to systemic sclerosis and
      is not associated with systemic sclerosis disease phenotype.
AB  - OBJECTIVES: Multiple studies indicate the role of the interleukin (IL)-17/IL-23
      axis in autoimmune diseases, including systemic sclerosis (SSc). The aim of the
      current study was to investigate the possible implication of the IL23R gene in
      SSc susceptibility and/or clinical phenotype. METHODS: An initial case-control
      study in 143 Dutch patients with SSc and geographically matched healthy
      individuals (n = 246) was carried out and followed by a replication study in a
      cohort of 365 Spanish patients with SSc and 515 healthy individuals. Seven single
      nucleotide polymorphisms (SNPs) spanning the IL23R gene were selected and
      genotyped using a Taqman assay. RESULTS: Using a Dutch cohort of patients with
      SSc and controls we observed an association between two (rs11209032, rs1495965)
      of the seven tested SNPs and disease susceptibility (allelic p values: p = 0.02
      and p = 0.01 respectively). However, a replication study in an independent
      Spanish cohort did not confirm these findings and reveal no association of any of
      the IL23R-tested SNP with disease susceptibility or clinical phenotype.
      Similarly, a meta-analysis considering both populations did not reveal any
      significant association. In addition, no association was observed between IL23R
      genetic variants and SSc clinical phenotypes. CONCLUSIONS: Our results suggest
      that the IL23R gene is not associated with SSc susceptibility or clinical
      phenotype.

PMID- 18713789
TI  - A toolkit for analysing large-scale plant small RNA datasets.
AB  - Recent developments in high-throughput sequencing technologies have generated
      considerable demand for tools to analyse large datasets of small RNA sequences.
      Here, we describe a suite of web-based tools for processing plant small RNA
      datasets. Our tools can be used to identify micro RNAs and their targets, compare
      expression levels in sRNA loci, and find putative trans-acting siRNA loci.
      AVAILABILITY: The tools are freely available for use at http://srna
      tools.cmp.uea.ac.uk.

PMID- 18713788
TI  - Strontium ranelate reduces the risk of vertebral fracture in young postmenopausal
      women with severe osteoporosis.
AB  - OBJECTIVES: Early osteoporotic fractures have a great impact on disease
      progression, the first fracture being a major risk factor for further fractures.
      Strontium ranelate efficacy against vertebral fractures is presently assessed in
      a subset of women aged 50-65 years. METHODS: The Spinal Osteoporosis Therapeutic
      Intervention (SOTI) was an international, double blind, placebo controlled trial,
      supporting the efficacy of strontium ranelate 2 g/day in reducing the risk of
      vertebral fractures in postmenopausal women with osteoporosis and a prevalent
      vertebral fracture. 353 of these randomly assigned women were included in this
      analysis. RESULTS: Over 4 years, strontium ranelate significantly reduced the
      risk of vertebral fracture by 35% (relative risk 0.65; 95% CI 0.42 to 0.99,
      p<0.05). In the strontium ranelate group, the bone mineral density increased from
      baseline by 15.8% at lumbar spine and 7.1% at femoral neck. CONCLUSION: These
      data demonstrate a significant vertebral antifracture efficacy of strontium
      ranelate in young postmenopausal women aged 50-65 years with severe osteoporosis
      and confirm the efficacy of this antiosteoporotic treatment to prevent vertebral
      fractures, whatever the age of the patient.

PMID- 18713790
TI  - ITFP: an integrated platform of mammalian transcription factors.
AB  - Investigation of transcription factors (TFs) and their downstream regulated genes
      (targets) is a significant issue in post-genome era, which can provide a brand
      new vision for some vital biological process. However, information of TFs and
      their targets in mammalian is far from sufficient. Here, we developed an
      integrated TF platform (ITFP), which included abundant TFs and their targets of
      mammalian. In current release, ITFP includes 4105 putative TFs and 69 496
      potential TF-target pairs for human, 3134 putative TFs and 37 040 potential TF
      target pairs for mouse, and 1114 putative TFs and 18 055 potential TF-target
      pairs for rat. In short, ITFP will serve as an important resource for the
      research community of transcription and provide strong support for regulatory
      network study.

PMID- 18713792
TI  - Disability and survival in Duchenne muscular dystrophy.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) leads to progressive impairment of
      muscle function, respiratory failure and premature death. Longitudinal data on
      the course of physical disability and respiratory function are sparse.
      OBJECTIVES: To assess prospectively physical impairment and disability,
      respiratory function and survival in patients with DMD over several years to
      describe the course of the disease with current care. METHODS: In 43 patients
      with DMD, aged 5-35 years, yearly assessments of physical disability by the
      Duchenne muscular dystrophy physical Impairment and Dependence on care (DID)
      score, ranging from 9 (no disability) to 80 (complete dependence), and forced
      vital capacity (FVC), were obtained over a mean time interval of 5.4 (SD 2.1)
      years. RESULTS: DID scores were correlated with age according to a hyperbolic
      function (f = 85.3 x age/(10.05+age), R = 0.62, p<0.0001). FVC declined
      exponentially with age (f = 139.1 x exp(-0.08 x age), R = 0.52, p<0.0001). Mean
      age at which patients lost their ambulation was 9.4 (SD 2.4) years and they
      became dependent on an electric wheelchair at 14.6 (4.0) years. Age at the
      beginning of assisted ventilation was 19.8 (3.9) years, Three patients died
      during the observation period. The estimated probability of survival to age 30
      years was 85% (median survival was 35 years). CONCLUSIONS: Our detailed
      observations of the progression of physical disability, dependence on care and
      respiratory impairment in patients with DMD from childhood to adult life is
      valuable for predicting the clinical course with current medical care. Compared
      with historical data, survival has improved considerably.

PMID- 18713791
TI  - Model-based analysis of interferon-beta induced signaling pathway.
AB  - MOTIVATION: Interferon-beta induced JAK-STAT signaling pathways contribute to
      mucosal immune recognition and an anti-viral state. Though the main molecular
      mechanisms constituting these pathways are known, neither the detailed structure
      of the regulatory network, nor its dynamics has yet been investigated. The
      objective of this work is to build a mathematical model for the pathway that
      would serve two purposes: (1) to reproduce experimental results in simulation of
      both early and late response to Interferon-beta stimulation and (2) to explain
      experimental phenomena generating new hypotheses about regulatory mechanisms that
      cannot yet be tested experimentally. RESULTS: Experimentally determined time
      dependent changes in the major components of this pathway were used to build a
      mathematical model describing pathway dynamics in the form of ordinary
      differential equations. The experimental results suggested existence of unknown
      negative control mechanisms that were tested numerically using the model.
      Together, experimental and numerical data show that the epithelial JAK-STAT
      pathway might be subjected to previously unknown dynamic negative control
      mechanisms: (1) activation of dormant phosphatases and (2) inhibition of nuclear
      import of IRF1.

PMID- 18713793
TI  - High frequency of submicroscopic genomic aberrations detected by tiling path
      array comparative genome hybridisation in patients with isolated congenital heart
      disease.
AB  - BACKGROUND: Congenital heart disease (CHD) is the most common birth defect and
      affects nearly 1% of newborns. The aetiology of CHD is largely unknown and only a
      small percentage can be assigned to environmental risk factors such as maternal
      diseases or exposure to mutagenic agents during pregnancy. Chromosomal imbalances
      have been identified in many forms of syndromic CHD, but very little is known
      about the impact of DNA copy number changes in non-syndromic CHD. METHOD: A sub
      megabase resolution array comparative genome hybridisation (CGH) screen was
      carried out on 105 patients with CHD as the sole abnormality at the time of
      diagnosis. RESULTS: There were 18 chromosomal changes detected, which do not
      coincide with common DNA copy number variants, including one de novo deletion,
      two de novo duplications and eight familial copy number variations (one deletion
      and seven duplications). CONCLUSIONS: Our data show that submicroscopic deletions
      and duplications play an important role in the aetiology of this condition,
      either as direct causes or as genetic risk factors for CHD. These findings have
      immediate consequences for genetic counselling and should pave the way for the
      elucidation of the pathogenetic mechanisms underlying CHD.

PMID- 18713794
TI  - Spinal subdural haematomas in children with non-accidental head injury.
AB  - OBJECTIVE: To examine the incidence of spinal pathology in infants with non
      accidental head injury. METHODS: 18 infants with non-accidental head injury were
      investigated between 2000 and 2007 with dedicated MRI of the brain and spine.
      During the earlier years, the spine was imaged only when there were suspicious
      features on other imaging to suggest a spinal injury (seven cases). After 2005,
      all suspected cases of non-accidental head injury were routinely investigated
      with MRI of the whole spine in addition to the brain. The spinal imaging at
      initial investigation and at follow-up was reviewed. RESULTS: There was a high
      incidence (8/18 cases, 44%) of subdural collections in the spine. They were all
      clinically occult and in six cases large. All eight cases were associated with
      subdural haematomas in the supratentorial and infratentorial compartment. The
      signal characteristics were analysed and compared with those of the intracranial
      collections. One had a small epidural haematoma. Other depicted abnormalities and
      appearances at follow-up were also reviewed. CONCLUSION: There is a high
      incidence of previously unsuspected spinal subdural haematomas associated with
      intracranial collections in children with non-accidental head injury. Further
      work is required to evaluate the clinical implications.

PMID- 18713795
TI  - Currently recommended treatments of childhood constipation are not evidence
      based: a systematic literature review on the effect of laxative treatment and
      dietary measures.
AB  - INTRODUCTION: Constipation is a common complaint in children and early
      intervention with oral laxatives may improve complete resolution of functional
      constipation. However, most treatment guidelines are based on reviews of the
      literature that do not incorporate a quality assessment of the studies.
      OBJECTIVE: To investigate and summarise the quantity and quality of the current
      evidence for the effect of laxatives and dietary measures on functional childhood
      constipation. METHODS: The Medline and Embase databases were searched to identify
      studies evaluating the effect of a medicamentous treatment or dietary
      intervention on functional constipation. Methodological quality was assessed
      using a validated list of criteria. Data were statistically pooled, and in case
      of clinical heterogeneity results were summarised according to a best evidence
      synthesis. RESULTS: Of the 736 studies found, 28 met the inclusion criteria. In
      total 10 studies were of high quality. The included studies were clinically and
      statistically heterogeneous in design. Most laxatives were not compared to
      placebo. Compared to all other laxatives, polyethylene glycol (PEG) achieved more
      treatment success (pooled relative risk (RR): 1.47; 95% CI 1.23 to 1.76).
      Lactulose was less than or equally effective in increasing the defecation
      frequency compared to all other laxatives investigated. There was no difference
      in effect on defecation frequency between fibre and placebo (weighted
      standardised mean difference 0.35 bowel movements per week in favour of fibre,
      95% CI -0.04 to 0.74). CONCLUSION: Insufficient evidence exists supporting that
      laxative treatment is better than placebo in children with constipation. Compared
      to all other laxatives, PEG achieved more treatment success, but results on
      defecation frequency were conflicting. Based on the results of this review, we
      can give no recommendations to support one laxative over the other for childhood
      constipation.

PMID- 18713796
TI  - Spray bacteriotherapy decreases middle ear fluid in children with secretory
      otitis media.
AB  - OBJECTIVE: Secretory otitis media (SOM) is characterised by persistent fluid in
      the middle ear cavity, but the cause is unknown. We investigated the clinical,
      bacteriological and immunological effects of treatment with probiotic bacteria on
      SOM. DESIGN: In this double-blind pilot/preliminary study, 60 children with long
      standing SOM (median 6 months) who were scheduled for insertion of tympanostomy
      tubes were randomised to nasal spray treatment with Streptococcus sanguinis,
      Lactobacillus rhamnosus or placebo for 10 days before surgery. Clinical
      evaluation was carried out after 10 days of treatment. Middle ear fluid (MEF) was
      collected during surgery for quantification of cytokines and detection of
      bacteria by culture and polymerase chain reaction (PCR). Nasopharyngeal swabs
      were obtained before treatment and at surgery. RESULTS: Complete or significant
      clinical recovery occurred in 7/19 patients treated with S sanguinis compared to
      1/17 patients in the placebo group (p<0.05). In the L rhamnosus treatment group,
      3/18 patients were cured or much better (p = 0.60 compared with placebo). Spray
      treatment did not alter the composition of the nasopharyngeal flora or the
      cytokine pattern observed in the nasopharynx or MEF, except for a higher level of
      IL-8 found in the nasopharynx of L rhamnosus treated children. CONCLUSIONS: This
      study shows that spray treatment with S sanguinis may be effective against SOM.
      The mechanism for the effect remains to be investigated.

PMID- 18713797
TI  - Saturated fatty acids inhibit hepatic insulin action by modulating insulin
      receptor expression and post-receptor signalling.
AB  - Free fatty acids (FFAs) are proposed to play a pathogenic role in both peripheral
      and hepatic insulin resistance. We have examined the effect of saturated FFA on
      insulin signalling (100 nM) in two hepatocyte cell lines. Fao hepatoma cells were
      treated with physiological concentrations of sodium palmitate (0.25 mM) (16:0)
      for 0.25-48 h. Palmitate decreased insulin receptor (IR) protein and mRNA
      expression in a dose- and time-dependent manner (35% decrease at 12 h). Palmitate
      also reduced insulin-stimulated IR and IRS-2 tyrosine phosphorylation, IRS-2
      associated PI 3-kinase activity, and phosphorylation of Akt, p70 S6 kinase, GSK-3
      and FOXO1A. Palmitate also inhibited insulin action in hepatocytes derived from
      wild-type IR (+/+) mice, but was ineffective in IR-deficient (-/-) cells. The
      effects of palmitate were reversed by triacsin C, an inhibitor of fatty acyl CoA
      synthases, indicating that palmitoyl CoA ester formation is critical. Neither the
      non-metabolized bromopalmitate alone nor the medium chain fatty acid octanoate
      (8:0) produced similar effects. However, the CPT-1 inhibitor (+/-)-etomoxir and
      bromopalmitate (in molar excess) reversed the effects of palmitate. Thus, the
      inhibition of insulin signalling by palmitate in hepatoma cells is dependent upon
      oxidation of fatty acyl-CoA species and requires intact insulin receptor
      expression.

PMID- 18713798
TI  - Inhibition of human immunodeficiency virus type 1 replication by blocking IkappaB
      kinase with noraristeromycin.
AB  - Nuclear factor kappaB (NF-kappaB) is one of the critical transcription factors in
      inflammatory responses and replication of viruses such as human immunodeficiency
      virus (HIV). In fact, it has been demonstrated that various NF-kappaB inhibitors
      could block HIV replication. To explore more potent NF-kappaB inhibitors, we
      focused on carbocyclic adenine nucleosides that had been reported to have anti
      inflammatory effects. We synthesized 15 carbocyclic adenine nucleoside compounds
      and examined their effects on the NF-kappaB-dependent gene expression using
      HEK293 cell line. Among these compounds, noraristeromycin (NAM) exhibited the
      most potent inhibitory effect on the NF-kappaB activity under the non-cytotoxic
      concentrations. NAM-inhibited IkappaBalpha phosphorylation and degradation upon
      stimulation of cells with tumour necrosis factor-alpha (TNF-alpha). In addition,
      NAM prevented p65 phoshorylation. These findings suggested that both IkappaB
      kinase-alpha (IKK-alpha) and -beta were targeted by NAM. Interestingly, in vitro
      kinase assay revealed that NAM inhibited the kinase activity of IKK-alpha more
      potently than that of IKK-beta. When we treated the cell lines, OM10.1 and
      Molt4/IIIB, in which HIV-1 is latently and chronically infected, we found a
      strong suppressive effect of NAM on HIV-1 viral replication upon stimulation with
      TNF-alpha.

PMID- 18713799
TI  - Construction of a fully synthetic human scFv antibody library with CDR3 regions
      randomized by a split-mix-split method and its application.
AB  - The randomization scheme of hypervariable region takes crucial role in
      construction of a synthetic antibody library. The codon bias and inevitable
      'stop' codon of conventional 'NNK' and 'NNS' codons limit their applications.
      Here we report a split-mix-split DNA synthesis method that can control over the
      amino acid composition and distribution of randomized sequences effectually. A
      fully synthetic human antibody library with a diversity of 1.56 x 10(9) was
      successfully generated with complementarity determining region 3 (CDR3)
      randomized by this strategy. Sequencing analysis indicated that >60% of colonies
      had completely correct scFv genes and the amino acid composition and distribution
      were designed well in accordance. The utility was demonstrated by screening of
      scFv clones against BHL (anti-CD3 x anti-ovarian carcinoma bispecific antibody).
      These results proved the feasibility of the split-mix-split DNA randomization
      strategy in library construction and site-directed mutagenesis.

PMID- 18713800
TI  - Hideyo Noguchi Africa Prize. Tightening the net around malaria.

PMID- 18713802
TI  - Tackling malaria today.

PMID- 18713803
TI  - Academic performance of ethnic minorities in medical school.

PMID- 18713804
TI  - Dare to use your own intelligence.

PMID- 18713807
TI  - Cocaine use in England and Wales rises as cannabis use falls.

PMID- 18713808
TI  - Childhood immunisation against varicella zoster virus.

PMID- 18713810
TI  - Conservative non-pharmacological treatment for chronic low back pain.

PMID- 18713809
TI  - Randomised controlled trial of Alexander technique lessons, exercise, and massage
      (ATEAM) for chronic and recurrent back pain.
AB  - OBJECTIVE: To determine the effectiveness of lessons in the Alexander technique,
      massage therapy, and advice from a doctor to take exercise (exercise
      prescription) along with nurse delivered behavioural counselling for patients
      with chronic or recurrent back pain. DESIGN: Factorial randomised trial. SETTING:
      64 general practices in England. PARTICIPANTS: 579 patients with chronic or
      recurrent low back pain; 144 were randomised to normal care, 147 to massage, 144
      to six Alexander technique lessons, and 144 to 24 Alexander technique lessons;
      half of each of these groups were randomised to exercise prescription.
      INTERVENTIONS: Normal care (control), six sessions of massage, six or 24 lessons
      on the Alexander technique, and prescription for exercise from a doctor with
      nurse delivered behavioural counselling. MAIN OUTCOME MEASURES: Roland Morris
      disability score (number of activities impaired by pain) and number of days in
      pain. RESULTS: Exercise and lessons in the Alexander technique, but not massage,
      remained effective at one year (compared with control Roland disability score
      8.1: massage -0.58, 95% confidence interval -1.94 to 0.77, six lessons -1.40, 
      2.77 to -0.03, 24 lessons -3.4, -4.76 to -2.03, and exercise -1.29, -2.25 to 
      0.34). Exercise after six lessons achieved 72% of the effect of 24 lessons alone
      (Roland disability score -2.98 and -4.14, respectively). Number of days with back
      pain in the past four weeks was lower after lessons (compared with control median
      21 days: 24 lessons -18, six lessons -10, massage -7) and quality of life
      improved significantly. No significant harms were reported. CONCLUSIONS: One to
      one lessons in the Alexander technique from registered teachers have long term
      benefits for patients with chronic back pain. Six lessons followed by exercise
      prescription were nearly as effective as 24 lessons. TRIAL REGISTRATION: National
      Research Register N0028108728.

PMID- 18713811
TI  - The Golgi CMP-sialic acid transporter: A new CHO mutant provides functional
      insights.
AB  - A CHO mutant line, MAR-11, was isolated using a cytotoxic lectin, Maackia
      amurensis agglutinin (MAA). This mutant has decreased levels of cell surface
      sialic acid relative to both wild-type CHO-K1 and Lec2 mutant CHO cells. The CMP
      sialic acid transporter (CMP-SAT) gene in the MAR-11 mutant cell has a C-T
      mutation that results in a premature stop codon. As a result, MAR-11 cells
      express a truncated version of CMP-SAT which contains only 100 amino acids rather
      than the normal CMP-SAT which contains 336 amino acids. Biochemical analyses
      indicate that recombinant interferon-gamma (IFN-gamma) produced by the mutant
      cells lack sialic acid. Using MAR-11 as host cells, an EPO/IEF assay for the
      structure-function study of CMP-SAT was developed. This assay seems more
      sensitive than previous assays that were used to analyze sialylation in Lec2
      cells. Cotransfection of constructs that express CMP-SAT into MAR-11 cells
      completely converted the recombinant EPO to a sialylation pattern that is similar
      to the EPO produced by the wild-type CHO cells. Using this assay, we showed that
      CMP-SAT lacking C-terminal 18 amino acids from the cytosolic tail was able to
      allow high levels of EPO sialylation. Substitution of the Gly residues with Ile
      in three different transmembrane domains of CMP-SAT resulted in dramatic
      decreases in transporter's activity. The CMP-SAT only lost partial activity if
      the same Gly residues were substituted with Ala, suggesting that the lack of side
      chain in Gly residues in the transmembrane domains is essential for transport
      activity.

PMID- 18713812
TI  - Vesicle-associated protein 1: a novel ovarian immunocontraceptive target in the
      common brushtail possum, Trichosurus vulpecula.
AB  - Ovarian-based immunological research is currently restricted to proteins of the
      zona pellucida. This study examined the immunocontraceptive potential of a novel
      vesicle-associated protein, VAP1, previously isolated from the vesicle-rich
      hemisphere of the brushtail possum oocyte. Seven female possums were immunized
      against recombinant glutathione S-transferase-VAP1 fusion protein. Control
      animals (n=3) received antigen-free vaccinations. Following immunization, regular
      blood sampling determined the level and duration of immune response. Animals were
      monitored daily, pre- and post-immunization, to determine estrous cycling
      activity and the percentage of reproductive cycles yielding viable young. The
      reproductive tracts and somatic organs of VAP1-immunized (n=7), control-immunized
      (n=3) and non-immunized (n=5) animals were collected and examined by histology
      and transmission electron microscopy. VAP1 immunization caused a strong and
      sustained immune response. Elevated levels of VAP1 antibody binding were detected
      in sera following initial injections, and immune titers rose as boosters were
      administered. Immunization had no adverse effect upon animal behavior or body
      condition. Immunized females demonstrated no major change in annual estrous
      cycling activity; however, the percentage of reproductive cycles resulting in
      pouch young decreased significantly (P<0.05) by 40%. Histological and
      ultrastructural analyses revealed an abundance of lipid-like degradation bodies
      within the ooplasm of developing oocytes and the cytoplasm of failing uterine
      zygotes. Active macrophage invasion of enlarged endometrial glands was observed
      in the uteri of two females. Reproductive tract changes are discussed in relation
      to observed fertility decline. The results of this study indicate that VAP1 has
      exciting potential as an immunocontraceptive target for possum control in New
      Zealand.

PMID- 18713813
TI  - Retinoid X receptor beta (RXRB) expression in Sertoli cells controls cholesterol
      homeostasis and spermiation.
AB  - Somatic, targeted inactivation of the retinoid X receptor beta gene (Rxrb) in
      Sertoli cells (SC; yielding Rxrb(Ser-/-) mutants) leads to failure of spermatid
      release, accumulation of cholesterol esters and, subsequently, testis
      degeneration. These abnormalities are identical, in their nature and kinetics, to
      those observed upon inactivating Rxrb in the whole organism, thereby
      demonstrating that all reproductive functions of RXRB are carried out in SC. The
      Rxrb(Ser-/-) testis degeneration is a consequence of a cholesterol ester cell
      overload occurring in SC in response to reduced ABCA1- and SCARB1-mediated
      cholesterol efflux. The failure of spermiation was also reported in mice lacking
      the retinoic acid (RA) receptor-alpha (RARA) in SC (Rara(Ser-/-) mutants) and
      represents, in addition, a feature of vitamin A deficiency that can be readily
      induced in mice lacking the lecithin:retinol acyltransferase (Lrat(-/-) mutants).
      Altogether, these findings support the conclusion that RXRB heterodimerized with
      a RA-liganded RARA transduces signals required in SC for spermatid release.

PMID- 18713816
TI  - AIDS treatment specialists take on prevention.

PMID- 18713817
TI  - Deoxyribonucleic acid profiling analysis of 40 human thyroid cancer cell lines
      reveals cross-contamination resulting in cell line redundancy and
      misidentification.
AB  - CONTEXT: Cell lines derived from human cancers provide critical tools to study
      disease mechanisms and develop novel therapies. Recent reports indicate that up
      to 36% of cell lines are cross- contaminated. OBJECTIVE: We evaluated 40 reported
      thyroid cancer-derived cell lines using short tandem repeat and single nucleotide
      polymorphism array analysis. RESULTS: Only 23 of 40 cell lines tested have unique
      genetic profiles. The following groups of cell lines are likely derivatives of
      the same cell line: BHP5-16, BHP17-10, BHP14-9, and NPA87; BHP2-7, BHP10-3, BHP7
      13, and TPC1; KAT5, KAT10, KAT4, KAT7, KAT50, KAK1, ARO81-1, and MRO87-1; and K1
      and K2. The unique cell lines include BCPAP, KTC1, TT2609-C02, FTC133, ML1, WRO82
      1, 8505C, SW1736, Cal-62, T235, T238, Uhth-104, ACT-1, HTh74, KAT18, TTA1, FRO81
      2, HTh7, C643, BHT101, and KTC-2. The misidentified cell lines included the DRO90
      1, which matched the melanoma-derived cell line, A-375. The ARO81-1 and its
      derivatives matched the HT-29 colon cancer cell line, and the NPA87 and its
      derivatives matched the M14/MDA-MB-435S melanoma cell line. TTF-1 and Pax-8 mRNA
      levels were determined in the unique cell lines. CONCLUSIONS: Many of these human
      cell lines have been widely used in the thyroid cancer field for the past 20 yr
      and are not only redundant, but not of thyroid origin. These results emphasize
      the importance of cell line integrity, and provide the short tandem repeat
      profiles for a panel of thyroid cancer cell lines that can be used as a reference
      for comparison of cell lines from other laboratories.

PMID- 18713818
TI  - Physiological androgen insensitivity of the fetal, neonatal, and early infantile
      testis is explained by the ontogeny of the androgen receptor expression in
      Sertoli cells.
AB  - CONTEXT: Although gonadotropins and testosterone are high in the fetal/early
      postnatal periods, Sertoli cells remain immature and spermatogenesis does not
      progress. We hypothesized that Sertoli cells do not respond to testosterone
      because they do not express the androgen receptor. OBJECTIVE: The objective of
      the study was to describe the precise ontogeny of androgen receptor expression in
      the human testis from fetal life through adulthood. DESIGN: This was an
      immunohistochemical study on testicular biopsies from fetal, neonatal,
      prepubertal, pubertal, and adult human testes. MAIN OUTCOME MEASURES:
      Quantification of androgen receptor expression in Sertoli cells was measured.
      Evaluation of androgen receptor expression in peritubular and interstitial cells
      as well as anti-Mullerian hormone and inhibin-alpha was also performed. RESULTS:
      Androgen receptor expression was first observed in the nuclei of few Sertoli
      cells at the age of 5 months. Labeling was weak in 2-15% of Sertoli cells until 4
      yr of age and progressively increased thereafter. High levels of androgen
      receptor expression were observed in more than 90% from the age of 8 yr through
      adulthood. Androgen receptor was positive in peritubular cells and variable in
      interstitial cells. Anti-Mullerian hormone immunolabeling was strong in all
      Sertoli cells from fetal life throughout prepuberty and weakened progressively as
      spermatogenesis developed. Inhibin-alpha expression was detected in all Sertoli
      cells from fetal life through adulthood. CONCLUSIONS: A lack of androgen receptor
      expression could explain a physiological Sertoli cell androgen insensitivity
      during fetal and early postnatal life, which may serve to protect the testis from
      precocious Sertoli cell maturation, resulting in proliferation arrest and
      spermatogenic development.

PMID- 18713819
TI  - Development of an adrenocorticotropin-responsive human adrenocortical carcinoma
      cell line.
AB  - CONTEXT: The molecular mechanisms regulating adrenal steroidogenesis continue to
      be defined. The only current human adrenocortical cell line is the NCI-H295 and
      its substrains. One of the strains, H295R, has retained the ability to respond to
      angiotensin II (Ang II); however, it lacks ACTH responsiveness. An ACTH
      responsive human adrenocortical model would add significantly to studies directed
      at defining the molecular control of corticosteroid biosynthesis. OBJECTIVE: The
      objective of the study was to develop a human adrenal cell line that retained
      both Ang II- and ACTH-regulated corticosteroid production. DESIGN: Human
      adrenocortical carcinoma (HAC) cells were isolated from an adrenal tumor removed
      from a girl presenting with virilization and hypertension. Clonal populations of
      cells were established and characterized. HAC cells were treated with ACTH, Ang
      II, and forskolin, followed by examination of steroidogenic enzyme mRNA
      expression using quantitative real-time PCR and steroid production. RESULTS: HAC
      clone 15 (HAC15) cells responded to treatment with ACTH, Ang II, and forskolin,
      with increased cortisol and aldosterone production. ACTH, Ang II, and forskolin
      also increased expression of mRNA, encoding all enzymes needed for cortisol and
      aldosterone biosynthesis, namely steroidogenic acute regulatory protein,
      cholesterol side-chain cleavage, cytochrome P450 17alpha-hydroxylase-17, 20
      lyase, 3beta-hydroxysteroid dehydrogenase type II, 21-hydroxylase, 11beta
      hydroxylase, and 11beta-aldosterone synthase. In addition, the cells expressed
      mRNA for ACTH receptor (MC2R) and Ang II receptor. MC2R protein was also
      expressed in HAC15 cells. CONCLUSION: The current study describes the development
      and characterization of an ACTH- and Ang II-responsive human adrenal cell line.
      The HAC15 cell line should provide an important model system for defining the
      molecular mechanisms regulating aldosterone and cortisol production.

PMID- 18713820
TI  - Reproducibility of the oral glucose tolerance test in overweight children.
AB  - OBJECTIVE: We examined the reproducibility of the oral glucose tolerance test
      (OGTT) in overweight children and evaluated distinguishing characteristics
      between those with concordant vs. discordant results. DESIGN: Sixty overweight
      youth (8-17 yr old) completed two OGTTs (interval between tests 1-25 d). Insulin
      sensitivity was assessed by the surrogate measures of fasting glucose to insulin
      ratio, whole-body insulin sensitivity index, and homeostasis model assessment of
      insulin resistance, and insulin secretion by the insulinogenic index with
      calculation of the glucose disposition index (GDI). RESULTS: Of the 10 subjects
      with impaired glucose tolerance (IGT) during the first OGTT only three (30%) had
      IGT during the second OGTT. The percent positive agreement between the first and
      second OGTT was low for both impaired fasting glucose and IGT (22.2 and 27.3%,
      respectively). Fasting blood glucose had higher reproducibility, compared with
      the 2-h glucose. Youth with discordant OGTTs, compared with those with concordant
      results, were more insulin resistant (glucose/insulin 2.7+/-1.4 vs. 4.1+/-1.8,
      P=0.006, whole-body insulin sensitivity index of 1.3+/-0.6 vs. 2.2+/-1.1,
      P=0.003, and homeostasis model assessment of insulin resistance 10.6+/-8.1 vs.
      5.7+/-2.8, P=0.001), had a lower GDI (0.45+/-0.58 vs. 1.02+/-1.0, P=0.03), and
      had higher low-density lipoprotein cholesterol (117.7+/-36.6 vs. 89.9+/-20.1,
      P=0.0005) without differences in physical characteristics. CONCLUSIONS: Our
      results show poor reproducibility of the OGTT in obese youth, in particular for
      the 2-h plasma glucose. Obese youth who have discordant OGTT results are more
      insulin resistant with higher risk of developing type 2 diabetes mellitus, as
      evidenced by a lower GDI. The implications of this remain to be determined in
      clinical and research settings.

PMID- 18713821
TI  - Oxysterol as a marker of atherogenic dyslipidemia in adolescence.
AB  - CONTEXT: Oxysterols represent potentially important oxidative stress biomarkers
      in adolescence. OBJECTIVE: The objective of the study was to examine the
      relationship between the concentrations of serum enzymatically and
      nonenzymatically generated oxysterols, measures of obesity, and metabolic
      components including insulin resistance and levels of blood pressure and serum
      lipids. DESIGN: This was a cross-sectional study. SETTING: All subjects were
      examined between 2003 and 2005 at a hospital, a part of a follow-up evaluation
      mother-daughter pairs representing pregnancies affected or unaffected by
      gestational diabetes that resulted in the deliveries in 1989-1991. SUBJECTS:
      Subjects included a subset (n=89) of the total study population of 189 adolescent
      girls with a mean age of 15.32+/-0.65 yr and body mass index of 22.54+/-3.98
      kg/m2. MAIN OUTCOME MEASURES: Measures included serum levels of the oxysterols
      7alpha-hydroxy-cholesterol, 7beta-hydroxycholesterol, and 7-ketocholesterol; and
      body mass index, homeostasis model assessment insulin resistance index, fasting
      insulin, fasting glucose, blood pressure, total cholesterol, non-high-density
      lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol, triglycerides, and apolipoprotein B (ApoB). RESULTS:
      Serum oxysterol concentrations in the adolescent cohort correlated positively
      with insulin (P<0.05), total cholesterol (P<0.05), non-high-density lipoprotein
      cholesterol (P<0.05), low-density lipoprotein cholesterol (P<0.05), and ApoB
      (P<0.01). ApoB and fasting insulin were found to be the major determinants of
      serum oxysterols after adjustment for body mass index. Being a daughter of
      gestational diabetes pregnancy alone did not seem to be a predisposing factor to
      increased oxidative stress in our cohort. CONCLUSION: Serum oxysterol
      concentrations increase with obesity, insulin, and ApoB, which are established
      derangements associated with the metabolic syndrome.

PMID- 18713822
TI  - Fatty acid metabolism in patients with PPARgamma mutations.
AB  - CONTEXT: PPARG mutations may cause insulin resistance and dyslipidemia, but
      little is known about the mechanisms of the abnormalities of lipid metabolism.
      OBJECTIVE: We hypothesized that in PPARG mutations, abnormal adipose tissue
      triglyceride storage causes insulin resistance. DESIGN, PATIENTS, AND MAIN
      OUTCOME MEASURES: Whole-body and adipose tissue-specific metabolic phenotyping
      through arteriovenous blood sampling was made before and after a mixed meal
      including 13C-palmitic acid. Studies were performed in a 32-yr-old male with
      partial lipodystrophy and type 2 diabetes, heterozygous for the PPARG P467L
      mutation and in an apparently phenotypically normal 32-yr-old male heterozygous
      for the PPARG n.AAA553T mutation. Comparator groups were age- and sex-matched
      healthy participants (n=10) and type 2 diabetes sex-matched participants (n=6).
      RESULTS: The P467L patient had elevated unmodulated fasting and postprandial
      plasma nonesterified fatty acid (NEFA) concentrations, despite a low adipose
      tissue NEFA output. Instead, NEFA appeared to originate directly from
      triglyceride-rich lipoproteins: 13C-palmitic acid accumulated rapidly in the NEFA
      fraction, as a sign of impaired fatty acid trapping in tissues. In contrast to
      the Pparg haploinsufficient mouse, the patient with n.AAA553T mutation did not
      exhibit paradoxically insulin sensitive and showed a mostly normal metabolic
      pattern. CONCLUSIONS: The lipodystrophic PPARG P467L phenotype include excessive
      and uncontrolled generation of NEFA directly from triglyceride-rich lipoproteins,
      explaining high systemic NEFA concentrations, whereas the human PPARG
      haploinsufficiency is metabolically almost normal.

PMID- 18713823
TI  - Effects of weight loss after bariatric surgery for morbid obesity on vascular
      endothelial growth factor-A, adipocytokines, and insulin.
AB  - BACKGROUND: Adipocytes regulate blood vessel formation, and in turn endothelial
      cells promote preadipocyte differentiation through the expression of
      proangiogenic factors, such as vascular endothelial growth factor (VEGF)-A. Some
      adipocytokines and hormones also have an effect on vascular development.
      OBJECTIVES: Our objectives were to analyze the relationship between weight and
      circulating VEGF-A in morbidly obese subjects before and after bariatric surgery,
      and investigate the relationship between circulating VEGF-A and certain
      adipocytokines and hormones regulating adipocytes. METHODS: A total of 45
      morbidly obese women and nine lean females were included in the study. Patients
      underwent bariatric surgery: vertical banded gastroplasty (n=17), gastric bypass
      (n=17), and biliopancreatic diversion (n=11). Serum samples for VEGF-A,
      adiponectin, leptin, ghrelin, and insulin were obtained preoperatively and 9-12
      months after surgery. RESULTS: Obese patients showed significantly higher VEGF-A
      levels than controls (306.3+/-170.3 vs. 187.6+/-91.9 pg/ml; P=0.04), decreasing
      to 246.1+/-160.4 after surgery (P<0.001), with no differences among surgical
      procedures. In controls there was an inverse correlation between VEGF-A and
      ghrelin (r=-0.85; P<.01), but not in obese patients. Leptin and insulin
      concentrations were increased in obese patients, with a significant decrease
      shown after weight loss with surgery. Conversely, adiponectin concentrations were
      lower in obese patients, with a significant increase shown after weight loss with
      surgery. Ghrelin was higher in controls than obese patients, decreasing after
      gastric bypass and biliopancreatic diversion, but not after vertical banded
      gastroplasty. CONCLUSION: Serum VEGF-A levels are significantly higher in obese
      patients than in lean controls, decreasing after weight loss with bariatric
      surgery, behaving similarly to other hormones related to adipose mass like leptin
      and insulin.

PMID- 18713824
TI  - Variation in flooding-induced morphological traits in natural populations of
      white clover (Trifolium repens) and their effects on plant performance during
      soil flooding.
AB  - BACKGROUND AND AIMS: Soil flooding leads to low soil oxygen concentrations and
      thereby negatively affects plant growth. Differences in flooding tolerance have
      been explained by the variation among species in the extent to which traits
      related to acclimation were expressed. However, our knowledge of variation within
      natural species (i.e. among individual genotypes) in traits related to flooding
      tolerance is very limited. Such data could tell us on which traits selection
      might have taken place, and will take place in future. The aim of the present
      study was to show that variation in flooding-tolerance-related traits is present
      among genotypes of the same species, and that both the constitutive variation and
      the plastic variation in flooding-induced changes in trait expression affect the
      performance of genotypes during soil flooding. METHODS: Clones of Trifolium
      repens originating from a river foreland were subjected to either drained,
      control conditions or to soil flooding. Constitutive expression of morphological
      traits was recorded on control plants, and flooding-induced changes in expression
      were compared with these constitutive expression levels. Moreover, the effect of
      both constitutive and flooding-induced trait expression on plant performance was
      determined. KEY RESULTS: Constitutive and plastic variation of several
      morphological traits significantly affected plant performance. Even relatively
      small increases in root porosity and petiole length contributed to better
      performance during soil flooding. High specific leaf area, by contrast, was
      negatively correlated with performance during flooding. CONCLUSIONS: The data
      show that different genotypes responded differently to soil flooding, which could
      be linked to variation in morphological trait expression. As flooded and drained
      conditions exerted different selection pressures on trait expression, the optimal
      value for constitutive and plastic traits will depend on the frequency and
      duration of flooding. These data will help us understanding the mechanisms
      affecting short- and long-term dynamics in flooding-prone ecosystems.

PMID- 18713825
TI  - Health information technology: strategic initiatives, real progress.
AB  - We fully agree with Carol Diamond and Clay Shirky that deployment of health
      information technology (IT) is necessary but not sufficient for transforming U.S.
      health care. However, the recent work to advance health IT is far from an
      exercise in "magical thinking." It has been strategic thinking. To illustrate
      this, we highlight recent initiatives and progress under four focus areas:
      adoption, governance, privacy and security, and interoperability. In addition,
      solutions exist for health IT to advance rapidly without adversely affecting
      future policy choices. A broad national consensus is emerging in support of
      advancing health IT to enable the transformation of health and care.

PMID- 18713826
TI  - The alternative route: hanging out the unmentionables for better decision making
      in health information technology.
AB  - Expert panels and policy analysts have often ignored potential contributions to
      health information technology (IT) from the Internet and Web-based applications.
      Perhaps they are among the "unmentionables" of health IT. Ignoring those
      unmentionables and relying on established industry experts has left us with a
      standards process that is complex and burdened by diverse goals, easy for
      entrenched interests to dominate, and reluctant to deal with potentially
      disruptive technologies. We need a health IT planning process that is more
      dynamic in its technological forecasting and inclusive of IT experts from outside
      the industry.

PMID- 18713827
TI  - Health information technology: a few years of magical thinking?
AB  - One of the biggest obstacles to expanding the use of information technology (IT)
      in health care may be the current narrow focus on how to stimulate its adoption.
      The challenge of thinking of IT as a tool to improve quality requires serious
      attention to transforming the U.S. health care system as a whole, rather than
      simply computerizing the current setup. Proponents of health IT must resist
      "magical thinking," such as the notion that technology will transform our broken
      system, absent integrated work on policy or incentives. The alternative route to
      transforming the system sets all of its sights on the destination.

PMID- 18713828
TI  - Possible relationship between the risk of Japanese bladder cancer cases and the
      CYP4B1 genotype.
AB  - Cytochrome P450 4B1 (CYP4B1) is involved in the metabolism of several
      xenobiotics, such as 2-aminofluorene, 2-naphthylamine and benzidine. CYP4B1
      allelic variants CYP4B1*1-*7 were recently identified. We thus hypothesized that
      CYP4B1 genotypes may modify bladder cancer risk. We examined the CYP4B1 genotypes
      in 169 bladder cancer cases and 190 hospital controls using a hybridization probe
      assay. Among the CYP4B1 genotypes observed, the most frequent genotypes in both
      the groups were CYP4B1*1/*1, *1/*2, *1/*3 and *2/*2. Logistic regression analysis
      revealed that the subjects carrying the CYP4B1*1/*2 or *2/*2 genotypes had a 1.75
      fold increased risk of bladder cancer (95% CI=1.03-2.95, P = 0.038) compared with
      the subjects carrying the CYP4B1*1/*1 genotype. We demonstrated the first genetic
      study regarding the association of CYP4B1 with bladder cancer. Our results
      suggest that CYP4B1 genotypes might have an effect on the risk of bladder cancer.

PMID- 18713829
TI  - Translational public health: rehearsing the evidence until the task is done.

PMID- 18713830
TI  - VRK1 phosphorylates CREB and mediates CCND1 expression.
AB  - Vaccinia virus B1 kinase plays a key role in viral DNA replication. The
      homologous mammalian vaccinia-related kinases (VRKs) are also implicated in the
      regulation of DNA replication, although direct evidence remains elusive. Here we
      show that VRK1 regulates cell cycle progression in the DNA replication period by
      inducing cyclin D1 (CCND1) expression. Furthermore, depletion of VRK1 in human
      cancer cells reduces the fraction of cells in S phase at a given time. VRK1
      specifically enhances activity of the cAMP-response element (CRE) in the CCND1
      promoter by facilitating the recruitment of phospho-CREB to this locus. VRK1
      phosphorylates CREB at Ser133 in vitro and the expression of a kinase-dead mutant
      of VRK1 or knockdown of VRK1 using siRNA fails to activate CREB and subsequently
      activate CRE. Finally, we show that VRK1 is a critical link in the CCND1 gene
      expression pathway stimulated by Myc overexpression. Our results indicate that
      VRK1 is a novel regulator of CCND1 expression.

PMID- 18713831
TI  - Synapsin-I- and synapsin-II-null mice display an increased age-dependent
      cognitive impairment.
AB  - Synapsin I (SynI) and synapsin II (SynII) are major synaptic vesicle (SV)
      proteins that function in the regulation of the availability of SVs for release
      in mature neurons. SynI and SynII show a high level of sequence similarity and
      share many functions in vivo, although distinct physiological roles for the two
      proteins have been proposed. Both SynI(-/-) and SynII(-/-) mice have a normal
      lifespan, but exhibit a decreased number of SVs and synaptic depression upon high
      frequency stimulation. Because of the role of the synapsin proteins in synaptic
      organization and plasticity, we studied the long-lasting effects of synapsin
      deletion on the phenotype of SynI(-/-) and SynII(-/-) mice during aging. Both
      SynI(-/-) and SynII(-/-) mice displayed behavioural defects that emerged during
      aging and involved emotional memory in both mutants, and spatial memory in SynII(
      /-) mice. These abnormalities, which were more pronounced in SynII(-/-) mice,
      were associated with neuronal loss and gliosis in the cerebral cortex and
      hippocampus. The data indicate that SynI and SynII have specific and non
      redundant functions, and that synaptic dysfunctions associated with synapsin
      mutations negatively modulate cognitive performances and neuronal survival during
      senescence.

PMID- 18713832
TI  - Cytosolic PLA2(alpha) activation in Purkinje neurons and its role in AMPA
      receptor trafficking.
AB  - Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) selectively releases arachidonic
      acid from membrane phospholipids and has been proposed to be involved in the
      induction of long-term depression (LTD), a form of synaptic plasticity in the
      cerebellum. This enzyme requires two events for its full activation: Ca(2+)
      dependent translocation from the cytosol to organelle membranes in order to
      access phospholipids as substrates, and phosphorylation by several kinases.
      However, the subcellular distribution and activation of cPLA(2)alpha in Purkinje
      cells and the role of arachidonic acid in cerebellar LTD have not been fully
      elucidated. In cultured Purkinje cells, stimulation of AMPA receptors, but not
      metabotropic glutamate receptors, triggered translocation of cPLA(2)alpha to the
      somatic and dendritic Golgi compartments. This translocation required Ca(2+)
      influx through P-type Ca(2+) channels. AMPA plus PMA, a chemical method for
      inducing LTD, released arachidonic acid via phosphorylation of cPLA(2)alpha. AMPA
      plus PMA induced a decrease in surface GluR2 for more than 2 hours.
      Interestingly, this reduction was occluded by a cPLA(2)alpha-specific inhibitor.
      Furthermore, PMA plus arachidonic acid caused the prolonged internalization of
      GluR2 without activating AMPA receptors. These results suggest that cPLA(2)alpha
      regulates the persistent decrease in the expression of AMPA receptors,
      underscoring the role of cPLA(2)alpha in cerebellar LTD.

PMID- 18713833
TI  - The regulated exocytosis of enlargeosomes is mediated by a SNARE machinery that
      includes VAMP4.
AB  - The mechanisms governing the fast, regulated exocytosis of enlargeosomes have
      been unknown, except for the participation of annexin-2 in a pre-fusion step. We
      investigated whether any SNAREs are involved. In PC12-27 cells, which are
      enlargeosome-rich, the expressed SNAREs exhibited various distributions (trans
      Golgi network, scattered puncta, plasma membrane); however, only VAMP4 was
      colocalized in discrete puncta with the enlargeosome marker desmoyokin. The
      exocytosis of the organelle, revealed by capacitance increases and by surface
      appearance of desmoyokin, was largely inhibited by microinjection of anti-VAMP4,
      anti-syntaxin-6 and anti-SNAP23 antibodies, by incubation with botulinum toxin E,
      and by transfection of VAMP4 and syntaxin-6 siRNAs. Microinjection of the
      antibodies anti-VAMP7, anti-VAMP8 and anti-syntaxin-4, and transfection with the
      VAMP8 siRNA were ineffective. Inhibition of enlargeosome exocytosis by VAMP4
      siRNA also occurred in a cell type that was competent for neurosecretion, SH
      SY5Y. Moreover, in cells expressing a VAMP4-GFP construct, enlargeosome
      exocytosis and surface appearance of fluorescence occurred concomitantly, and
      many ensuing surface patches were co-labelled by GFP and desmoyokin. VAMP4, an R
      SNARE that has never been shown to participate in regulated exocytoses, therefore
      appears to be harboured in the membrane of enlargeosomes and to be a member of
      the machinery mediating their regulated exocytosis. Syntaxin-6 and SNAP23 appear
      also to be needed for the process to occur; however, the mechanism of their
      participation, whether direct or indirect, remains undefined.

PMID- 18713834
TI  - Heat shock causes a decrease in polysomes and the appearance of stress granules
      in trypanosomes independently of eIF2(alpha) phosphorylation at Thr169.
AB  - In trypanosomes there is an almost total reliance on post-transcriptional
      mechanisms to alter gene expression; here, heat shock was used to investigate the
      response to an environmental signal. Heat shock rapidly and reversibly induced a
      decrease in polysome abundance, and the consequent changes in mRNA metabolism
      were studied. Both heat shock and polysome dissociation were necessary for (1) a
      reduction in mRNA levels that was more rapid than normal turnover, (2) an
      increased number of P-body-like granules that contained DHH1, SCD6 and XRNA, (3)
      the formation of stress granules that remained largely separate from the P-body
      like granules and localise to the periphery of the cell and, (4) an increase in
      the size of a novel focus located at the posterior pole of the cell that contain
      XRNA, but neither DHH1 nor SCD6. The response differed from mammalian cells in
      that neither the decrease in polysomes nor stress-granule formation required
      phosphorylation of eIF2alpha at the position homologous to that of serine 51 in
      mammalian eIF2alpha and in the occurrence of a novel XRNA-focus.

PMID- 18713835
TI  - Efficient coupling of Sec23-Sec24 to Sec13-Sec31 drives COPII-dependent collagen
      secretion and is essential for normal craniofacial development.
AB  - The COPII coat assembles on endoplasmic reticulum membranes to coordinate the
      collection of secretory cargo with the formation of transport vesicles. During
      COPII assembly, Sar1 deforms the membrane and recruits the Sec23-Sec24 complex
      (Sec23/24), which is the primary cargo-binding adaptor for the system, and Sec13
      Sec31 (Sec13/31), which provides a structural outer layer for vesicle formation.
      Here we show that Sec13 depletion results in concomitant loss of Sec31 and
      juxtanuclear clustering of pre-budding complexes containing Sec23/24 and cargo.
      Electron microscopy reveals the presence of curved coated profiles on distended
      endoplasmic reticulum, indicating that Sec13/31 is not required for the
      generation or maintenance of the curvature. Surprisingly, export of tsO45-G-YFP,
      a marker of secretory cargo, is unaffected by Sec13/31 depletion; by contrast,
      secretion of collagen from primary fibroblasts is strongly inhibited. Suppression
      of Sec13 expression in zebrafish causes defects in proteoglycan deposition and
      skeletal abnormalities that are grossly similar to the craniofacial abnormalities
      of crusher mutant zebrafish and patients with cranio-lenticulo-sutural dysplasia.
      We conclude that efficient coupling of the inner (Sec23/24) and outer (Sec13/31)
      layers of the COPII coat is required to drive the export of collagen from the
      endoplasmic reticulum, and that highly efficient COPII assembly is essential for
      normal craniofacial development during embryogenesis.

PMID- 18713836
TI  - HIF1 transcription factor regulates laminin-332 expression and keratinocyte
      migration.
AB  - Epidermal wound repair is a complex process involving the fine orchestrated
      regulation of crucial cell functions, such as proliferation, adhesion and
      migration. Using an in vitro model that recapitulates central aspects of
      epidermal wound healing, we demonstrate that the transcription factor HIF1 is
      strongly stimulated in keratinocyte cultures submitted to mechanical injury.
      Signals generated by scratch wounding stabilise the HIF1alpha protein, which
      requires activation of the PI3K pathway independently of oxygen availability. We
      further show that upregulation of HIF1alpha plays an essential role in
      keratinocyte migration during the in vitro healing process, because HIF1alpha
      inhibition dramatically delays the wound closure. In this context, we demonstrate
      that HIF1 controls the expression of laminin-332, one of the major epithelial
      cell adhesion ligands involved in cell migration and invasion. Indeed, silencing
      of HIF1alpha abrogates injury-induced laminin-332 expression, and we provide
      evidence that HIF1 directly regulates the promoter activity of the laminin alpha3
      chain. Our results suggest that HIF1 contributes to keratinocyte migration and
      thus to the re-epithelialisation process by regulating laminin-332.

PMID- 18713837
TI  - FFAT rescues VAPA-mediated inhibition of ER-to-Golgi transport and VAPB-mediated
      ER aggregation.
AB  - The VAMP-associated proteins termed VAP are a small gene family of proteins
      characterised by the presence of an N-terminal major sperm protein (MSP) domain.
      The P56S mutation of the B isoform (VAPB) has been linked to late-onset
      amyotrophic lateral sclerosis (ALS8) and its expression causes formation of large
      ER aggregates. Overexpression of the wild-type A isoform (VAPA) but not the B
      isoform (VAPB), inhibited ER-to-Golgi transport of membrane proteins. This
      transport block by VAPA was primarily due to decreased segregation of membrane
      cargo into ER vesicles. We also found that VAPA inhibited lateral diffusion of
      membrane proteins, most likely through its stable association with microtubules.
      The MSP domain of VAP is known to interact with the FFAT motif (two
      phenylalanines in an acidic tract) of proteins involved in sterol regulation.
      Overexpression of FFAT restored ER-to-Golgi transport and lateral diffusion of
      membrane proteins, and resolved the large ER aggregates in VAPB-P56S. Application
      of a FFAT peptide restored in vitro ER vesicle budding and disrupted VAP
      microtubule association. Thus, overexpression of the two VAP isoforms causes
      retention of ER membrane proteins by impeding lateral diffusion and their
      incorporation into transport vesicles. This inhibitory effect can be relieved by
      expression of the FFAT motif.

PMID- 18713839
TI  - S-adenosylhomocysteine hydrolase downregulation contributes to tumorigenesis.
AB  - With the idea to discover novel genes involved in proliferation, we have
      performed a genome-wide loss-of-function genetic screen to identify additional
      putative tumor suppressor genes. We have previously identified five genes
      belonging to different biochemical families. In this report, we focused on the
      study of one of these genes designated S-adenosylhomocysteine hydrolase (SAHH),
      which has also been previously identified in an independent short hairpin RNA
      screening. SAHH inactivation confers resistance to both p53 and p16(INK4)-induced
      proliferation arrest. Interestingly, SAHH inactivation inhibits p53
      transcriptional activity and impairs DNA damage-induced transcription of
      p21(Cip1). Given that SAHH downregulation modulates senescence in primary cells,
      we also studied SAHH expression in human tumors at the messenger RNA (mRNA) and
      protein levels. SAHH mRNA was lost in 50% of tumor tissues from 206 patients with
      different kinds of tumors in comparison with normal tissue counterparts.
      Moreover, SAHH protein was also affected in some colon cancers. Such findings may
      be of relevance to cancer research, suggesting that SAHH might be a largely
      unexplored tumor suppressor.

PMID- 18713838
TI  - Fibulin-5 initiates epithelial-mesenchymal transition (EMT) and enhances EMT
      induced by TGF-beta in mammary epithelial cells via a MMP-dependent mechanism.
AB  - Epithelial-mesenchymal transition (EMT) is a normal physiological process that
      regulates tissue development, remodeling and repair; however, aberrant EMT also
      elicits disease development in humans, including lung fibrosis, rheumatoid
      arthritis and cancer cell metastasis. Transforming growth factor-beta (TGF-beta)
      is a master regulator of EMT in normal mammary epithelial cells (MECs), wherein
      this pleiotropic cytokine also functions as a potent suppressor of mammary
      tumorigenesis. In contrast, malignant MECs typically evolve resistance to TGF
      beta-mediated cytostasis and develop the ability to proliferate, invade and
      metastasize when stimulated by TGF-beta. It therefore stands to reason that
      establishing how TGF-beta promotes EMT may offer new insights into targeting the
      oncogenic activities of TGF-beta in human breast cancers. By monitoring
      alterations in the actin cytoskeleton and various markers of EMT, we show here
      that the TGF-beta gene target, fibulin-5 (FBLN5), initiates EMT and enhances that
      induced by TGF-beta. Whereas normal MECs contain few FBLN5 transcripts, those
      induced to undergo EMT by TGF-beta show significant upregulation of FBLN5
      messenger RNA, suggesting that EMT and the dedifferentiation of MECs override the
      repression of FBLN5 expression in polarized MECs. We also show that FBLN5
      stimulated matrix metalloproteinase expression and activity, leading to MEC
      invasion and EMT, to elevated Twist expression and to reduced E-cadherin
      expression. Finally, FBLN5 promoted anchorage-independent growth in normal and
      malignant MECs, as well as enhanced the growth of 4T1 tumors in mice. Taken
      together, these findings identify a novel EMT and tumor-promoting function for
      FBLN5 in developing and progressing breast cancers.

PMID- 18713840
TI  - Akt phosphorylates the TR3 orphan receptor and blocks its targeting to the
      mitochondria.
AB  - Acutely transforming retrovirus AKT8 in rodent T cell lymphoma (Akt)
      phosphorylates and regulates the function of many cellular proteins involved in
      processes such as metabolism, apoptosis and proliferation. However, the precise
      mechanisms by which Akt promotes cell survival and inhibits apoptosis have been
      characterized in part only. TR3, an orphan receptor, functions as a transcription
      factor that can both positively or negatively regulate gene expression. We have
      reported previously that the translocation of TR3 from the nucleus to the
      mitochondria can elicit a proapoptotic effect in gastric cancer cells. In our
      present study, we demonstrate that Akt phosphorylates cytoplasmic TR3 through its
      physical interaction with the N-terminus of TR3. When coexpressed with Akt, TR3
      mitochondrial targeting was blocked and this protein adopted a diffuse expression
      pattern in the cytoplasm. Moreover, Akt displayed an ability to disrupt the
      interaction of TR3 with Bcl-2, which is thought to be a critical requirement for
      mitochondrial TR3 to elicit apoptosis. Consistently, insulin was also found to
      induce the phosphorylation of TR3 and abolish 12-O-tetradecanoylphorbol-13
      acetate-induced mitochondrial localization, which was dependent upon the
      activation of the phophatidylinositol-3-OH-kinase-Akt signaling pathway. Taken
      together, our current data demonstrate a unique role for Akt in inhibiting TR3
      functions that are not related to transcriptional activity but that correlate
      with the regulation of its mitochondrial association. This may represent a novel
      signal pathway by which Akt exerts its antiapoptotic effects in gastric cancer
      cells, i.e. by regulating the phosphorylation and redistribution of orphan
      receptors.

PMID- 18713841
TI  - GH replacement in hypopituitarism improves lipid profile and quality of life
      independently of changes in obesity variables.
AB  - OBJECTIVE: GH deficiency (GHD) in adults is characterized by elevated body mass
      index (BMI), increased waist girth (WG) and increased fat mass (FM). Information
      about how these indicators of obesity affect the lipid profile and quality of
      life (QoL) of GHD subjects is scarce. It is also unclear how changes in these
      indicators brought about by GH replacement influence lipids and QoL. DESIGN AND
      METHODS: Adult GHD subjects from the Pfizer International Metabolic Database were
      grouped according to BMI (n=291 with BMI <25 kg/m(2), n=372 with BMI 25-30
      kg/m(2), n=279 with BMI >30 kg/m(2)), WG (n=508 with normal WG, n=434 with
      increased WG) and FM (n=357) and according to changes in these variables after 1
      year of GH replacement. Serum IGF-I concentrations, lipid concentrations and QoL
      using the QoL Assessment of GHD in Adults questionnaire were assessed at baseline
      and after 1 year of treatment. RESULTS: At baseline, total and low-density
      lipoprotein (LDL) cholesterol were similarly elevated in the BMI and WG groups,
      but high-density lipoprotein (HDL) cholesterol decreased and triglycerides
      increased with increasing BMI and WG. QoL was progressively poorer with
      increasing BMI and WG. After 1 year of GH replacement, total and LDL cholesterol
      and QoL improved in all BMI, WG and FM groups. CONCLUSIONS: Variables of obesity
      adversely affect the already unfavourable lipid profile in GHD subjects by
      decreasing HDL cholesterol, but do not counteract the positive effect of GH
      replacement on LDL cholesterol. Similarly, QoL is influenced by obesity, but
      responds equally well to GH treatment independent of BMI, WG and FM.

PMID- 18713842
TI  - Hypocortisolemic clamp unmasks jointly feedforward- and feedback-dependent
      control of overnight ACTH secretion.
AB  - BACKGROUND: ACTH secretion is under hypothalamic stimulatory (feedforward) and
      adrenal inhibitory (feedback) control. HYPOTHESIS: Assessment of overnight ACTH
      secretion during a hypocortisolemic clamp will permit the estimation of changing
      feedforward and feedback. SUBJECTS: Seven healthy men. INTERVENTIONS: An oral
      dose of placebo (PLAC), metyrapone (METY, 3 g), or ketoconazole (KTCZ, 1.2 g) was
      given at midnight (MN) to block glucocorticoid synthesis. Plasma ACTH was sampled
      every 10 min (MN to 0800 h). ANALYSIS: Variable-waveform deconvolution analysis
      of ACTH secretion and approximate entropy (ApEn) analysis of pattern regularity.
      RESULTS: Compared with PLAC, administration of METY and KTCZ reduced morning
      cortisol concentrations by >or=77 and 54% respectively (P<0.001).
      Hypocortisolemia elevated pulsatile ACTH secretion by 8.2- (METY) and 5.3-fold
      (KTCZ; both P<0.001). Basal ACTH secretion rose by 3.4-fold under METY-induced
      cortisol depletion (P=0.020). ACTH secretory-burst shape and half-life were
      stable. ApEn of ACTH release declined overnight (P=0.021) and with the drug
      (P=0.001), denoting enhanced feedforward coordination. CONCLUSION: The combined
      data predict overnight amplification and coordination of hypothalamic feedforward
      drive onto ACTH release. Therefore, disruption of either mechanism might
      contribute to clinical pathophysiology, such as late-day elevations of cortisol
      output in fasting, alcoholism, depression, or aging.

PMID- 18713843
TI  - Thyroid papillary microcarcinoma: a descriptive and meta-analysis study.
AB  - The authors review anatomical, clinical characteristics and prevalence of thyroid
      microcarcinoma. Diagnostic procedures and risk factors of aggressiveness at
      diagnosis and during follow-up are also covered. The possible clinical,
      pathologic and therapeutic risk factors are analyzed by meta-analysis study.
      Treatment procedures by different authors and guidelines suggested by societies
      are reported.

PMID- 18713844
TI  - The combined low-dose dexamethasone suppression corticotropin-releasing hormone
      test as a tool to rule out Cushing's syndrome.
AB  - OBJECTIVE: It remains to be evaluated whether the combined low-dose dexamethasone
      suppression corticotropin-releasing hormone test (LDDST-CRH test) may add to the
      diagnostic approach of patients suspected to have Cushing's syndrome (CS). The
      aim of the present study was to evaluate whether the LDDST-CRH test may have a
      place in the diagnostic strategy of CS. DESIGN: Prospective evaluation of a
      consecutive series of patients with suspected CS from 2004 to 2006. METHODS: All
      the subjects underwent the same screening protocol including 1 mg dexamethasone
      suppression test, 24-h urinary free cortisol (UFC), and midnight serum cortisol,
      followed by the LDDST-CRH test whose results were not used to establish a
      definitive diagnosis. Plasma dexamethasone concentration was measured 2 h after
      the last dose of dexamethasone. Patients qualified for CS when at least two
      screening tests were positive. RESULTS: Sixteen patients had CS while in the
      remaining 15 subjects CS was excluded. Even if not statistically significant, the
      sensitivity and the negative predictive value of the cortisol 15 min after CRH
      were better than the other tests; on the other hand, the test specificity was
      lower. All of the patients classified as indeterminate were correctly diagnosed
      by the LDDST-CRH test. Nevertheless, the repeated assessment of the screening
      tests and the active follow-up gave the same correct results. In all of the
      patients misclassified by the LDDST-CRH test, the plasma dexamethasone
      concentrations were in the normal range. CONCLUSIONS: Based on our findings, we
      suggest that the LDDST-CRH test may still find a place as a rule-out procedure in
      patients who present with indeterminate results after screening and may be
      unavailable to repeat testing during follow-up.

PMID- 18713845
TI  - Are patient-administered attention deficit hyperactivity disorder scales suitable
      for adults?
AB  - OBJECTIVE: This primary purpose of this study was to examine cognitive complexity
      and readability of patient-administered ADHD scales. The secondary purpose was to
      estimate variation in readability of individual ADHD scale items. METHOD: Using
      comprehensive search strategies, we identified eight English-language ADHD scales
      for inclusion in our study. A complete copy of each ADHD scale was obtained from
      the most current publication. Cognitive complexity of individual ADHD scale items
      were assessed using three techniques (number of items, number of words, and
      linguistic problems), while readability was calculated using the Flesch-Kinkaid
      formula. RESULTS: Total number of ADHD scale items ranged from 6 to 66. The ADHD
      scale items averaged from a low of 4.4+/-2.9 to a high of 18.7+/-4.4 words. Most
      individual ADHD scale items had between 1 to 3 linguistic problems. Although
      readability of ADHD scales ranged from approximately 5th to 8th grade, there was
      notable variation in readability across individual statements and questions.
      CONCLUSION: Formatting characteristics, including linguistic problems and high
      readability, may interfere with patients' ability to accurately complete ADHD
      scales.

PMID- 18713846
TI  - Asthma, atopy, and airway inflammation: what does it mean in practice?

PMID- 18713847
TI  - Pseudomonas aeruginosa: an uninvited guest refuses to leave.

PMID- 18713848
TI  - Benefits of examining influenza vaccine associations outside of influenza season.

PMID- 18713849
TI  - Chronic obstructive pulmonary disease: a view from the NHLBI.

PMID- 18713850
TI  - Whole-body "negative-pressure" ventilation: is it really different?

PMID- 18713851
TI  - The INSPIRE study: influence of prior use and discontinuation of inhaled
      corticosteroids.

PMID- 18713852
TI  - Posaconazole: an oral triazole with an extended spectrum of activity.
AB  - OBJECTIVE: To summarize the published clinical data on posaconazole, critically
      review the New Drug Application data submitted to the Food and Drug
      Administration, and provide information critical for evaluation and formulary
      positioning. DATA SOURCES: Reported investigations were identified from MEDLINE
      (1966-June 30, 2008), bibliographies of manuscripts, www.clinicaltrials.gov, and
      www.fda.gov. STUDY SELECTION AND DATA EXTRACTION: English-language articles were
      selected. All available in vitro, animal, clinical, and human studies describing
      the pharmacology, pharmacokinetics, pharmacodynamics, efficacy, safety, and
      adverse events of posaconazole were reviewed. DATA SYNTHESIS: Posaconazole is an
      oral broad-spectrum triazole with activity against many yeasts and molds.
      Resistance to posaconazole has been reported, but has been rare to date.
      Posaconazole, in doses of 200 mg 3 times daily, reduced breakthrough invasive
      fungal infections (OR 0.30; 95% CI 0.12 to 0.71) and aspergillosis incidence (OR
      0.31; 95% CI 0.13 to 0.75) in patients receiving hematopoietic stem-cell
      transplants compared with those receiving fluconazole. Similarly, the same
      regimen of posaconazole reduced invasive fungal infections (95% CI -9.7 to -2.5)
      and aspergillosis (CI not reported, p < 0.001) when compared with fluconazole and
      itraconazole in neutropenic patients. Posaconazole is noninferior to fluconazole
      for treatment of oropharyngeal candidiasis (95% CI -6.6 to 5.0), but necessity
      for this indication remains unclear, as many other treatment options exist.
      Smaller investigations have analyzed use of posaconazole for patients requiring
      salvage or alternative treatment for zygomycosis, fusariosis, cryptococcal
      meningitis, coccidioidomycosis, and histoplasmosis. Studies are needed to clarify
      efficacy for such expanded use, and therapeutic drug monitoring may improve
      outcomes. The most common adverse effects associated with the use of posaconazole
      include headache, fever, nausea, vomiting, and diarrhea. CONCLUSIONS:
      Posaconazole appears to be a valuable and promising addition to the antifungal
      armamentarium for prophylaxis and treatment of various fungal processes. At this
      time, posaconazole should probably be reserved for prophylaxis in patients at
      high risk for invasive fungal infection, as salvage therapy in refractory or
      resistant infections, or for patients with intolerance to other therapies.

PMID- 18713853
TI  - Differences in the length of the carboxyl terminus mediate functional properties
      of neurokinin-1 receptor.
AB  - The neurokinin-1 receptor (NK1R) has two naturally occurring forms that differ in
      the length of the carboxyl terminus: a full-length receptor consisting of 407 aa
      and a truncated receptor consisting of 311 aa. We examined whether there are
      differential signaling properties attributable to the carboxyl terminus of this
      receptor by using stably transfected human embryonic kidney (HEK293) cell lines
      that express either full-length or truncated NK1R. Substance P (SP) specifically
      triggered intracellular calcium increase in HEK293 cells expressing full-length
      NK1R but had no effect in the cells expressing the truncated NK1R. In addition,
      in cells expressing full-length NK1R, SP activated NF-kappaB and IL-8 mRNA
      expression, but in cells expressing the truncated NK1R, SP did not activate NF
      kappaB, and it decreased IL-8 mRNA expression. In cells expressing full-length
      NK1R, SP stimulated phosphorylation of PKCdelta but inhibited phosphorylation of
      PKCdelta in cells expressing truncated NK1R. There are also differences in the
      timing of SP-induced ERK activation in cells expressing the two different forms
      of the receptor. Full-length NK1R activation of ERK was rapid (peak within 1-2
      min), whereas truncated NK1R-mediated activation was slower (peak at 20-30 min).
      Thus, the carboxyl terminus of NK1R is the structural basis for differences in
      the functional properties of the full-length and truncated NK1R. These
      differences may provide important information toward the design of new NK1R
      receptor antagonists.

PMID- 18713854
TI  - Neurogenetic networks for startle-induced locomotion in Drosophila melanogaster.
AB  - Understanding how the genome empowers the nervous system to express behaviors
      remains a critical challenge in behavioral genetics. The startle response is an
      attractive behavioral model for studies on the relationship between genes, brain,
      and behavior, as the ability to respond rapidly to harmful changes in the
      environment is a universal survival trait. Drosophila melanogaster provides a
      powerful system in which genetic studies on individuals with controlled genetic
      backgrounds and reared under controlled environmental conditions can be combined
      with neuroanatomical studies to analyze behaviors. In a screen of 720 lines of D.
      melanogaster, carrying single P[GT1] transposon insertions, we found 267 lines
      that showed significant changes in startle-induced locomotor behavior. Excision
      of the transposon reversed this effect in five lines out of six tested. We infer
      that most of the 267 lines show mutant effects on startle-induced locomotion that
      are caused by the transposon insertions. We selected a subset of 15 insertions in
      the same genetic background in autosomal genes with strong mutant effects and
      crossed them to generate all 105 possible nonreciprocal double heterozygotes.
      These hybrids revealed an extensive network of epistatic interactions on the
      behavioral trait. In addition, we observed changes in neuroanatomy that were
      caused by these 15 mutations, individually and in their double heterozygotes. We
      find that behavioral and neuroanatomical phenotypes are determined by a common
      set of genes that are organized as partially overlapping genetic networks.

PMID- 18713855
TI  - Differential involvement of striosome and matrix dopamine systems in a transgenic
      model of dopa-responsive dystonia.
AB  - Dopa-responsive dystonia (DRD) is a hereditary dystonia characterized by a
      childhood onset of fixed dystonic posture with a dramatic and sustained response
      to relatively low doses of levodopa. DRD is thought to result from striatal
      dopamine deficiency due to a reduced synthesis and activity of tyrosine
      hydroxylase (TH), the synthetic enzyme for dopamine. The mechanisms underlying
      the genesis of dystonia in DRD present a challenge to models of basal ganglia
      movement control, given that striatal dopamine deficiency is the hallmark of
      Parkinson's disease. We report here behavioral and anatomical observations on a
      transgenic mouse model for DRD in which the gene for 6-pyruvoyl-tetrahydropterin
      synthase is targeted to render selective dysfunction of TH synthesis in the
      striatum. Mutant mice exhibited motor deficits phenotypically resembling symptoms
      of human DRD and manifested a major depletion of TH labeling in the striatum,
      with a marked posterior-to-anterior gradient resulting in near total loss
      caudally. Strikingly, within the regions of remaining TH staining in the
      striatum, there was a greater loss of TH labeling in striosomes than in the
      surrounding matrix. The predominant loss of TH expression in striosomes occurred
      during the early postnatal period, when motor symptoms first appeared. We suggest
      that the differential striosome-matrix pattern of dopamine loss could be a key to
      identifying the mechanisms underlying the genesis of dystonia in DRD.

PMID- 18713856
TI  - Role of furin in granular acidification in the endocrine pancreas: identification
      of the V-ATPase subunit Ac45 as a candidate substrate.
AB  - Furin is a proprotein convertase which activates a variety of regulatory proteins
      in the constitutive exocytic and endocytic pathway. The effect of genetic
      ablation of fur was studied in the endocrine pancreas to define its physiological
      function in the regulated secretory pathway. Pdx1-Cre/loxP furin KO mice show
      decreased secretion of insulin and impaired processing of known PC2 substrates
      like proPC2 and proinsulin II. Both secretion and PC2 activity depend on granule
      acidification, which was demonstrated to be significantly decreased in furin
      deficient beta cells by using the acidotrophic agent 3-(2,4-dinitroanilino)
      3'amino-N-methyldipropylamine (DAMP). Ac45, an accessory subunit of the proton
      pump V-ATPase, was investigated as a candidate substrate. Ac45 is highly
      expressed in islets of Langerhans and furin was able to cleave Ac45 ex vivo.
      Furthermore, the exact cleavage site was determined. In addition, reduced
      regulated secretion and proinsulin II processing could be obtained in the
      insulinoma cell line betaTC3 by downregulation of either furin or Ac45. Together,
      these data establish an important role for furin in regulated secretion,
      particularly in intragranular acidification most likely due to impaired
      processing of Ac45.

PMID- 18713857
TI  - The intrinsic conformational propensities of the 20 naturally occurring amino
      acids and reflection of these propensities in proteins.
AB  - Here, we compare the distributions of main chain (Phi,Psi) angles (i.e.,
      Ramachandran maps) of the 20 naturally occurring amino acids in three contexts:
      (i) molecular dynamics (MD) simulations of Gly-Gly-X-Gly-Gly pentapeptides in
      water at 298 K with exhaustive sampling, where X = the amino acid in question;
      (ii) 188 independent protein simulations in water at 298 K from our Dynameomics
      Project; and (iii) static crystal and NMR structures from the Protein Data Bank.
      The GGXGG peptide series is often used as a model of the unstructured denatured
      state of proteins. The sampling in the peptide MD simulations is neither random
      nor uniform. Instead, individual amino acids show preferences for particular
      conformations, but the peptide is dynamic, and interconversion between conformers
      is facile. For a given amino acid, the (Phi,Psi) distributions in the protein
      simulations and the Protein Data Bank are very similar and often distinct from
      those in the peptide simulations. Comparison between the peptide and protein
      simulations shows that packing constraints, solvation, and the tendency for
      particular amino acids to be used for specific structural motifs can overwhelm
      the "intrinsic propensities" of amino acids for particular (Phi,Psi)
      conformations. We also compare our helical propensities with experimental
      consensus values using the host-guest method, which appear to be determined
      largely by context and not necessarily the intrinsic conformational propensities
      of the guest residues. These simulations represent an improved coil library free
      from contextual effects to better model intrinsic conformational propensities and
      provide a detailed view of conformations making up the "random coil" state.

PMID- 18713858
TI  - The Drosophila cohesin subunit Rad21 is a trithorax group (trxG) protein.
AB  - The cohesin complex is a key player in regulating cell division. Cohesin proteins
      SMC1, SMC3, Rad21, and stromalin (SA), along with associated proteins Nipped-B,
      Pds5, and EcoI, maintain sister chromatid cohesion before segregation to daughter
      cells during anaphase. Recent chromatin immunoprecipitation (ChIP) data reveal
      extensive overlap of Nipped-B and cohesin components with RNA polymerase II
      binding at active genes in Drosophila. These and other data strongly suggest a
      role for cohesion in transcription; however, there is no clear evidence for any
      specific mechanisms by which cohesin and associated proteins regulate
      transcription. We report here a link between cohesin components and trithorax
      group (trxG) function, thus implicating these proteins in transcription
      activation and/or elongation. We show that the Drosophila Rad21 protein is
      encoded by verthandi (vtd), a member of the trxG gene family that is also
      involved in regulating the hedgehog (hh) gene. In addition, mutations in the
      associated protein Nipped-B show similar trxG activity i.e., like vtd, they act
      as dominant suppressors of Pc and hh(Mrt) without impairing cell division. Our
      results provide a framework to further investigate how cohesin and associated
      components might regulate transcription.

PMID- 18713859
TI  - Stochastic hybrid modeling of DNA replication across a complete genome.
AB  - DNA replication in eukaryotic cells initiates from hundreds of origins along
      their genomes, leading to complete duplication of genetic information before cell
      division. The large number of potential origins, coupled with system uncertainty,
      dictates the need for new analytical tools to capture spatial and temporal
      patterns of DNA replication genome-wide. We have developed a stochastic hybrid
      model that reproduces DNA replication throughout a complete genome. The model can
      capture different modes of DNA replication and is applicable to various
      organisms. Using genome-wide data on the location and firing efficiencies of
      origins in the fission yeast, we show how the DNA replication process evolves
      during S-phase in the presence of stochastic origin firing. Simulations reveal
      small regions of the genome that extend S-phase to three times its reported
      duration. The low levels of late replication predicted by the model are below the
      detection limit of techniques used to measure S-phase length. Parameter
      sensitivity analysis shows that increased replication fork speeds genome-wide, or
      additional origins are not sufficient to reduce S-phase to its reported length.
      We model the redistribution of a limiting initiation factor during S-phase and
      show that it could shorten S-phase to the reported duration. Alternatively, S
      phase may be extended, and what has traditionally been defined as G2 may be
      occupied by low levels of DNA synthesis with the onset of mitosis delayed by
      activation of the G2/M checkpoint.

PMID- 18713860
TI  - Vibrio parahaemolyticus orchestrates a multifaceted host cell infection by
      induction of autophagy, cell rounding, and then cell lysis.
AB  - The bacterial pathogen Vibrio parahaemolyticus utilizes a type III secretion
      system to cause death of host cells within hours of infection. We report that
      cell death is completely independent of apoptosis and occurs by a mechanism in
      which injection of multiple type III effectors causes induction of autophagy,
      cell rounding, and the subsequent release of cellular contents. Autophagy is
      detected by the appearance of lipidated light chain 3 (LC3) and by increases in
      punctae and vacuole formation. Electron microscopy reveals the production of
      early autophagic vesicles during infection. Consistent with phosphoinositide 3
      (PI3) kinase playing a role in autophagy, treatment of infected cells with a PI3
      kinase inhibitor attenuates autophagy in infected cells. Because many effectors
      are injected during a V. parahaemolyticus infection, it is not surprising that
      the presence of a sole PI3 kinase inhibitor does not prevent inevitable host-cell
      death. Our studies reveal an infection paradigm whereby an extracellular pathogen
      uses its type III secretion system to cause at least three parallel events that
      eventually result in the proinflammatory death of an infected host cell.

PMID- 18713861
TI  - TRIM28 mediates primer binding site-targeted silencing of Lys1,2 tRNA-utilizing
      retroviruses in embryonic cells.
AB  - Murine leukemia viruses (MLVs) and related retroelements are potently restricted
      in embryonic cells by postintegration transcriptional silencing, likely to
      protect the germ line from insertional mutagenesis. This silencing is in large
      part attributable to the presence of a nuclear repression complex, which targets
      a sequence element of the proviral DNA, the repressor-binding site. The repressor
      binding site closely overlaps the tRNA primer binding site, a highly conserved
      sequence essential for virus replication and defining the site of initiation of
      DNA synthesis during reverse transcription. We have recently demonstrated that
      the cellular corepressor TRIM28 is recruited to the proline tRNA primer-binding
      site used by many MLVs and is required to mediate this silencing. Here, we show
      that TRIM28 is also required for the restriction of retroviruses using a
      completely distinct tRNA for the priming of their DNA synthesis, namely Lys-1,2
      tRNA. These results generalize the role of TRIM28 in retroviral restriction and
      suggest that this system has evolved to restrict multiple retroviruses.

PMID- 18713862
TI  - Crystal structures of fibronectin-binding sites from Staphylococcus aureus FnBPA
      in complex with fibronectin domains.
AB  - Staphylococcus aureus can adhere to and invade endothelial cells by binding to
      the human protein fibronectin (Fn). FnBPA and FnBPB, cell wall-attached proteins
      from S. aureus, have multiple, intrinsically disordered, high-affinity binding
      repeats (FnBRs) for Fn. Here, 30 years after the first report of S. aureus/Fn
      interactions, we present four crystal structures that together comprise the
      structures of two complete FnBRs, each in complex with four of the N-terminal
      modules of Fn. Each approximately 40-residue FnBR forms antiparallel strands
      along the triple-stranded beta-sheets of four sequential F1 modules ((2-5)F1)
      with each FnBR/(2-5)F1 interface burying a total surface area of approximately
      4,300 A(2). The structures reveal the roles of residues conserved between S.
      aureus and Streptococcus pyogenes FnBRs and show that there are few linker
      residues between FnBRs. The ability to form large intermolecular interfaces with
      relatively few residues has been proposed to be a feature of disordered proteins,
      and S. aureus/Fn interactions provide an unusual illustration of this efficiency.

PMID- 18713863
TI  - Selenoprotein N is required for ryanodine receptor calcium release channel
      activity in human and zebrafish muscle.
AB  - Mutations affecting the seemingly unrelated gene products, SepN1, a selenoprotein
      of unknown function, and RyR1, the major component of the ryanodine receptor
      intracellular calcium release channel, result in an overlapping spectrum of
      congenital myopathies. To identify the immediate developmental and molecular
      roles of SepN and RyR in vivo, loss-of-function effects were analyzed in the
      zebrafish embryo. These studies demonstrate the two proteins are required for the
      same cellular differentiation events and are needed for normal calcium fluxes in
      the embryo. SepN is physically associated with RyRs and functions as a modifier
      of the RyR channel. In the absence of SepN, ryanodine receptors from zebrafish
      embryos or human diseased muscle have altered biochemical properties and have
      lost their normal sensitivity to redox conditions, which likely accounts for why
      mutations affecting either factor lead to similar diseases.

PMID- 18713864
TI  - Evolution exacerbates the paradox of the plankton.
AB  - Can biodiversity evolve and persist in a uniform environment? This question is at
      the heart of the plankton paradox: in the natural world we observe many species
      sharing few resources, whereas the principle of competitive exclusion would lead
      us to expect that only a few species could coexist in such circumstances. To
      bridge the gap between theory and observation, previous studies have shown that
      the maximum number of species that can stably coexist is equal to the number of
      essential resources and that even more species can coexist out of equilibrium.
      These studies were viewed as a significant step toward a resolution of the
      paradox. Evolutionary dynamics, however, have been studied in this context only
      in limited cases, and it is largely unknown how mutations impact ecologically
      stable multispecies states, and whether large species consortia can spontaneously
      evolve. In the present study we introduce evolution to the standard ecological
      model of competition for essential resources. Combining numeric and analytic
      approaches, we find that ecologically stable species communities are severely
      destabilized by long-term evolutionary dynamics. Moreover, the number of species
      in spontaneously evolved consortia is much lower than the number of available
      resources. Contrary to expectations based on studies of two resources, these
      limits on biodiversity are not results of the occasional emergence of
      superspecies, superior to all competitors; nor are they alleviated by the
      inclusion of tradeoffs in resource utilization. Rather, we show that it is an
      accelerated depletion of limiting resources, combined with the essentiality of
      resources to all species, that leads invariably to catastrophic extinctions.

PMID- 18713865
TI  - High-resolution magnetic resonance histology of the embryonic and neonatal mouse:
      a 4D atlas and morphologic database.
AB  - Engineered mice play an ever-increasing role in defining connections between
      genotype and phenotypic expression. The potential of magnetic resonance
      microscopy (MRM) for morphologic phenotyping in the mouse has previously been
      demonstrated; however, applications have been limited by long scan times,
      availability of the technology, and a foundation of normative data. This article
      describes an integrated environment for high-resolution study of normal,
      transgenic, and mutant mouse models at embryonic and neonatal stages. Three
      dimensional images are shown at an isotropic resolution of 19.5 microm (voxel
      volumes of 8 pL), acquired in 3 h at embryonic days 10.5-19.5 (10 stages) and
      postnatal days 0-32 (6 stages). A web-accessible atlas encompassing this data was
      developed, and for critical stages of embryonic development (prenatal days 14.5
      18.5), >200 anatomical structures have been identified and labeled. Also,
      matching optical histology and analysis tools are provided to compare multiple
      specimens at multiple developmental stages. The utility of the approach is
      demonstrated in characterizing cardiac septal defects in conditional mutant
      embryos lacking the Smoothened receptor gene. Finally, a collaborative paradigm
      is presented that allows sharing of data across the scientific community. This
      work makes magnetic resonance microscopy of the mouse embryo and neonate broadly
      available with carefully annotated normative data and an extensive environment
      for collaborations.

PMID- 18713866
TI  - Overcoming multidrug resistance of small-molecule therapeutics through
      conjugation with releasable octaarginine transporters.
AB  - Many cancer therapeutic agents elicit resistance that renders them ineffective
      and often produces cross-resistance to other drugs. One of the most common
      mechanisms of resistance involves P-glycoprotein (Pgp)-mediated drug efflux. To
      address this problem, new agents have been sought that are less prone to inducing
      resistance and less likely to serve as substrates for Pgp efflux. An alternative
      to this approach is to deliver established agents as molecular transporter
      conjugates into cells through a mechanism that circumvents Pgp-mediated efflux
      and allows for release of free drug only after cell entry. Here we report that
      the widely used chemotherapeutic agent Taxol, ineffective against Taxol-resistant
      human ovarian cancer cell lines, can be incorporated into a releasable
      octaarginine conjugate that is effective against the same Taxol-resistant cell
      lines. It is significant that the ability of the Taxol conjugates to overcome
      Taxol resistance is observed both in cell culture and in animal models of ovarian
      cancer. The generality and mechanistic basis for this effect were also explored
      with coelenterazine, a Pgp substrate. Although coelenterazine itself does not
      enter cells because of Pgp efflux, its octaarginine conjugate does so readily.
      This approach shows generality for overcoming the multidrug resistance elicited
      by small-molecule cancer chemotherapeutics and could improve the prognosis for
      many patients with cancer and fundamentally alter search strategies for novel
      therapeutic agents that are effective against resistant disease.

PMID- 18713868
TI  - Competition between cryptic species explains variations in rates of lineage
      evolution.
AB  - Gradual evolution is a common phenomenon in the fossil record of marine
      microplankton, yet no theoretical model has so far been presented to explain the
      observed pattern of unidirectionality in trait evolution lasting over tens of
      millions of generations. Recent molecular genetic data show that the majority of
      microfossil-producing plankton groups harbors substantial cryptic diversity.
      Here, we examine the effect of cryptic diversity on apparent rates of lineage
      evolution. By using a theoretical approach, we show that under resource
      competition, an increasing number of sibling species within a hypothetical
      lineage leads to an exponential slowdown of the apparent rate of evolution. This
      mechanism explains both the remarkable variation in apparent rates of evolution
      observed in marine plankton, as well as the presence of long gradual evolutionary
      trends.

PMID- 18713867
TI  - BAFF activates Akt and Erk through BAFF-R in an IKK1-dependent manner in primary
      mouse B cells.
AB  - B cell activating factor (BAFF) signals through BAFF-R to promote mature B cell
      survival. Recent analyses of BAFF-induced signaling revealed direct association
      between augmented B cell metabolic fitness and activation of Akt, one of the key
      regulators of cell survival. The strongest and most reproducible induction of Akt
      occurs with significant delay (24 h) after BAFF treatment, where it precedes
      activation of anabolism. It was also recently shown that BAFF induces sustained
      Erk activation and increased turnover of the proapoptotic molecule Bim. Here we
      show that these BAFF-induced signaling pathways are mediated by BAFF-R and
      represent previously unknown arms of I kappa B kinase (IKK)1-dependent signaling.
      In combination with the known role of IKK1 in regulating transcription of
      prosurvival genes, our data underscore the central role of IKK1 in coordinating
      multiple BAFF-R-mediated signaling pathways controlling mature B cell
      homeostasis.

PMID- 18713869
TI  - Genome-wide search for yeast RNase P substrates reveals role in maturation of
      intron-encoded box C/D small nucleolar RNAs.
AB  - Ribonuclease P (RNase P) is an essential endonuclease responsible for the 5'-end
      maturation of precursor tRNAs. Bacterial RNase P also processes precursor 4.5S
      RNA, tmRNA, 30S preribosomal RNA, and several reported protein-coding RNAs.
      Eukaryotic nuclear RNase P is far more complex than in the bacterial form,
      employing multiple essential protein subunits in addition to the catalytic RNA
      subunit. RNomic studies have shown that RNase P binds other RNAs in addition to
      tRNAs, but no non-tRNA substrates have previously been identified. Additional
      substrates were identified by using a multipronged approach in the budding yeast
      Saccharomyces cerevisiae. First, RNase P-dependant changes in RNA abundance were
      examined on whole-genome microarrays by using strains containing temperature
      sensitive (TS) mutations in two of the essential RNase P subunits, Pop1p and
      Rpr1r. Second, RNase P was rapidly affinity-purified, and copurified RNAs were
      identified by using a genome-wide microarray. Third, to identify RNAs that do not
      change abundance when RNase P is depleted but accumulate as larger precursors,
      >80 potential small RNA substrates were probed directly by Northern blot analysis
      with RNA from the RNase P TS mutants. Numerous potential substrates were
      identified, of which we characterized the box C/D intron-encoded small nucleolar
      RNAs (snoRNAs), because these both copurify with RNase P and accumulate larger
      forms in the RNase P temperature-sensitive mutants. It was previously known that
      two pathways existed for excising these snoRNAs, one using the pre-mRNA splicing
      path and the other that was independent of splicing. RNase P appears to
      participate in the splicing-independent path for the box C/D intron-encoded
      snoRNAs.

PMID- 18713870
TI  - MS3D structural elucidation of the HIV-1 packaging signal.
AB  - The structure of HIV-1 Psi-RNA has been elucidated by a concerted approach
      combining structural probes with mass spectrometric detection (MS3D), which is
      not affected by the size and crystallization properties of target biomolecules.
      Distance constraints from bifunctional cross-linkers provided the information
      required for assembling an all-atom model from the high-resolution coordinates of
      separate domains by triangulating their reciprocal placement in 3D space. The
      resulting structure revealed a compact cloverleaf morphology stabilized by a long
      range tertiary interaction between the GNRA tetraloop of stemloop 4 (SL4) and the
      upper stem of stemloop 1 (SL1). The preservation of discrete stemloop structures
      ruled out the possibility that major rearrangements might produce a putative
      supersite with enhanced affinity for the nucleocapsid (NC) domain of the viral
      Gag polyprotein, which would drive genome recognition and packaging. The steric
      situation of single-stranded regions exposed on the cloverleaf structure offered
      a valid explanation for the stoichiometry exhibited by full-length Psi-RNA in the
      presence of NC. The participation of SL4 in a putative GNRA loop-receptor
      interaction provided further indications of the plasticity of this region of
      genomic RNA, which can also anneal with upstream sequences to stabilize
      alternative conformations of the 5' untranslated region (5'-UTR). Considering the
      ability to sustain specific NC binding, the multifaceted activities supported by
      the SL4 sequence suggest a mechanism by which Gag could actively participate in
      regulating the vital functions mediated by 5'-UTR. Substantiated by the 3D
      structure of Psi-RNA, the central role played by SL4 in specific RNA-RNA and
      protein-RNA interactions advances this domain as a primary target for possible
      therapeutic intervention.

PMID- 18713871
TI  - The dual-basin landscape in GFP folding.
AB  - Recent experimental studies suggest that the mature GFP has an unconventional
      landscape composed of an early folding event with a typical funneled landscape,
      followed by a very slow search and rearrangement step into the locked, active
      chromophore-containing structure. As we have shown previously, the substantial
      difference in time scales is what generates the observed hysteresis in
      thermodynamic folding. The interconversion between locked and the soft folding
      structures at intermediate denaturant concentrations is so slow that it is not
      observed under the typical experimental observation time. Simulations of a coarse
      grained model were used to describe the fast folding event as well as identify
      native-like intermediates on energy landscapes enroute to the fluorescent native
      fold. Interestingly, these simulations reveal structural features of the slow
      dynamic transition to chromophore activation. Experimental evidence presented
      here shows that the trapped, native-like intermediate has structural
      heterogeneity in residues previously linked to chromophore formation. We propose
      that the final step of GFP folding is a "locking" mechanism leading to
      chromophore formation and high stability. The combination of previous
      experimental work and current simulation work is explained in the context of a
      dual-basin folding mechanism described above.

PMID- 18713873
TI  - The evolution of anesthetic sensitivity and the evolution of a paper.

PMID- 18713874
TI  - Nicotine and postoperative management of pain.

PMID- 18713872
TI  - Identification and characterization of infiltrating macrophages in acetaminophen
      induced liver injury.
AB  - The role of macrophages in the pathogenesis of acetaminophen (APAP)-induced liver
      injury remains controversial, as it has been demonstrated that these cells
      display pro-toxicant and hepato-protective functions. This controversy may stem
      from the heterogeneity and/or plasticity of macrophages and the difficulty in
      distinguishing and differentially studying subpopulations of macrophages in the
      liver. In the present study, using flow cytometric analysis and fluorescence
      labeled antibodies against specific cell surface macrophage markers, we were able
      to, for the first time, identify an APAP-induced macrophage (IM) population
      distinct from resident Kupffer cells. The data demonstrated that the IMs were
      derived from circulating monocytes that infiltrated the liver following APAP
      induced liver injury. The IMs exhibited a phenotype consistent with that of
      alternatively activated macrophages and demonstrated the ability to phagocytize
      apoptotic cells and induce apoptosis of neutrophils. Furthermore, in the absence
      of the IMs, the resolution of hepatic damage following APAP-induced
      hepatotoxicity was delayed in CCR2(-/-) mice compared with wild-type mice. These
      findings likely contribute to the role of the IMs in the processes of tissue
      repair, including counteracting inflammation and promoting angiogenesis. The
      present study also demonstrated the ability of separating populations of
      macrophages and delineating distinct functions of each group in future studies of
      inflammatory disease in the liver and other tissues.

PMID- 18713875
TI  - Induction of heat shock protein 70 and preconditioning by sevoflurane: a potent
      protective interaction against myocardial ischemia-reperfusion injury.

PMID- 18713876
TI  - Introducing focused reviews in obstetric anesthesiology: a new series.

PMID- 18713877
TI  - It takes an entrepreneur.

PMID- 18713878
TI  - Introduction of new monitors into clinical anesthesia.

PMID- 18713879
TI  - Low-dose sevoflurane inhalation enhances late cardioprotection from the anti
      ulcer drug geranylgeranylacetone.
AB  - BACKGROUND: We investigated in rabbits whether sevoflurane enhances late
      cardioprotection induced by geranylgeranylacetone (GGA), a gastric antiulcer
      drug. METHODS: S(+)-ketamine and xylazine-anesthetized rabbits were assigned to
      one of seven experimental groups: a control (vehicle only) group, a GGA group, a
      sevoflurane group, a GGA+sevoflurane group, a sodium 5-hydroxydecanoate (5HD)
      group, a GGA + 5HD group, and a heat stress group. All rabbits were subjected to
      30 min of coronary artery occlusion followed by 3 h of reperfusion. Rabbits were
      pretreated with IV vehicle, GGA (10 mg/kg), or heat stress (42 degrees C for 15
      min) 24 h before coronary occlusion. Sevoflurane (0.5 minimum alveolar
      concentration) or 5HD (5 mg/kg) were administered before myocardial ischemia.
      Myocardial infarct size and the area at risk for ischemia were measured, and heat
      shock protein (Hsp) 70 levels in each experimental group were determined.
      RESULTS: Compared with vehicle only, GGA significantly reduced the size of
      myocardial infarction in relation to the area at risk (39 +/- 10% vs 59 +/- 9%, P
      < 0.02). Sevoflurane enhanced the GGA-induced cardioprotection (23 +/- 17%, P <
      0.05 vs GGA). The cardioprotective effect of GGA was abolished by administration
      of 5HD (56 +/- 15%, P < 0.01). GGA enhanced Hsp 70 expression compared with that
      in the control group (0.69 +/- 0.15 vs 0.36 +/- 0.05, P < 0.02). Administration
      of GGA with sevoflurane resulted in the same level of Hsp 70 expression as GGA
      (0.69 +/- 0.16, P > 0.98). CONCLUSIONS: GGA appears to reduce myocardial infarct
      size in association with increased Hsp 70 expression. Sevoflurane enhances the
      GGA-induced cardioprotective effect.

PMID- 18713880
TI  - The mechanism of helium-induced preconditioning: a direct role for nitric oxide
      in rabbits.
AB  - BACKGROUND: Helium produces preconditioning against myocardial infarction by
      activating prosurvival signaling, but whether nitric oxide (NO) generated by
      endothelial NO synthase plays a role in this phenomenon is unknown. We tested the
      hypothesis that NO mediates helium-induced cardioprotection in vivo. METHODS:
      Rabbits (n = 62) instrumented for hemodynamic measurement were subjected to a 30
      min left anterior descending coronary artery occlusion and 3 h reperfusion, and
      received 0.9% saline (control) or three cycles of 70% helium-30% oxygen
      administered for 5 min interspersed with 5 min of an air-oxygen mixture before
      left anterior descending coronary artery occlusion in the absence or presence of
      pretreatment with the nonselective NOS inhibitor N-nitro-l-arginine methyl ester
      (L-NAME; 10 mg/kg), the selective inducible NOS inhibitor aminoguanidine
      hydrochloride (AG; 300 mg/kg), or selective neuronal NOS inhibitor 7
      nitroindazole (7-NI; 50 mg/kg). In additional rabbits, the fluorescent probe 4,5
      diaminofluroscein diacetate (DAF-2DA) and confocal laser microscopy were used to
      detect NO production in the absence or presence of helium with or without L-NAME
      pretreatment. RESULTS: Helium reduced (P < 0.05) infarct size (24% +/- 4% of the
      left ventricular area at risk; mean +/- sd) compared with control (46% +/- 3%). L
      NAME, AG, and 7-NI did not alter myocardial infarct size when administered alone.
      L-NAME, but not 7-NI or AG, abolished helium-induced cardioprotection. Helium
      enhanced DAF-2DA fluorescence compared with control (26 +/- 8 vs 15 +/- 5 U,
      respectively). Pretreatment with L-NAME abolished these helium-induced increases
      in DAF-2DA fluorescence. CONCLUSIONS: The results indicate that cardioprotection
      by helium is mediated by NO that is probably generated by endothelial NOS in
      vivo.

PMID- 18713882
TI  - Attenuation of isoflurane-induced preconditioning and reactive oxygen species
      production in the senescent rat heart.
AB  - BACKGROUND: Although attenuation of anesthetic preconditioning in aged ex vivo
      heart models has been studied extensively, there are no comparable in vivo
      studies. To extend previous work and to address a possible mechanism underlying
      age-related differences, we investigated isoflurane-induced preconditioning and
      reactive oxygen species (ROS) production in the aged rat heart in vivo. METHODS:
      Male Fisher 344 rats were assigned from their respective age groups (young, 3-5
      mo; old, 20-24 mo) to either receive 30 min of 1.0 minimum alveolar concentration
      isoflurane or to a control group. Rats were subjected to coronary artery
      occlusion for 30 min followed by 2 h of reperfusion. A fluorescent probe for
      superoxide anion production (dihydroethidium, 1 mg) was administered in the
      absence of the isoflurane or just before isoflurane exposure in four additional
      groups. Myocardial infarct size and superoxide anion production were assessed
      using triphenyltetrazolium staining and epifluorescence microscopy, respectively.
      RESULTS: Isoflurane decreased myocardial infarct size of young rats (26.7% +/-
      3.0%) compared with young controls (50.9% +/- 1.9%; P < 0.001), whereas
      isoflurane did not significantly affect myocardial infarct size of old rats
      (39.1% +/- 0.9%) compared with old controls (46.5% +/- 2.4%; P > 0.05).
      Isoflurane increased ROS levels in young rats (430.5 +/- 95.9 arbitrary units
      [AU]) compared with young controls (162.7 +/- 25.5 AU; P < 0.01). In contrast, no
      significant changes in ROS levels were observed in old animals (316.4 +/- 56.3 AU
      isoflurane versus 233.8 +/- 59.2 AU control). CONCLUSIONS: Reduction in the
      cardioprotective effects of isoflurane and attenuation of isoflurane-stimulated
      ROS production were observed in the senescent myocardium in vivo.

PMID- 18713881
TI  - Inhibition of glycogen synthase kinase or the apoptotic protein p53 lowers the
      threshold of helium cardioprotection in vivo: the role of mitochondrial
      permeability transition.
AB  - BACKGROUND: Prosurvival signaling kinases inhibit glycogen synthase kinase-3beta
      (GSK-3beta) activity and stimulate apoptotic protein p53 degradation. Helium
      produces cardioprotection by activating prosurvival kinases, but whether GSK and
      p53 inhibition mediate this process is unknown. We tested the hypothesis that
      inhibition of GSK or p53 lowers the threshold of helium cardioprotection via a
      mitochondrial permeability transition pore (mPTP)-dependent mechanism. METHODS:
      Rabbits (n = 85) instrumented for hemodynamic measurement and subjected to a 30
      min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion
      received 0.9% saline (control), or 1, 3, or 5 cycles of 70% helium-30% oxygen
      administered for 5 min interspersed with 5 min of an air-oxygen mixture (fraction
      of inspired oxygen concentration = 0.30) before LAD occlusion. Other rabbits
      received the GSK inhibitor SB 216763 (SB21; 0.2 or 0.6 mg/kg), the p53 inhibitor
      pifithrin-alpha (PIF; 1.5 or 3.0 mg/kg), or SB21 (0.2 mg/kg) or PIF (1.5 mg/kg)
      plus helium (1 cycle) before LAD occlusion in the presence or absence of the mPTP
      opener atractyloside (5 mg/kg). RESULTS: Helium reduced (P < 0.05) myocardial
      infarct size (35 +/- 6 [n = 7], 25 +/- 4 [n = 7], and 20 +/- 3% [n = 6] of area
      at risk, 1, 3, and 5 cycles, respectively) compared with control (44 +/- 6% [n =
      7]). SB21 (0.6 [n = 7] but not 0.2 mg/kg [n = 6]) and PIF (3.0 [n = 6] but not
      1.5 mg/kg [n = 7]) also reduced necrosis. SB21 (0.2 mg/kg) or 1.5 mg/kg PIF (1.5
      mg/kg) plus helium (1 cycle; n = 6 per group) decreased infarct size to an
      equivalent degree as three cycles of helium alone, and this cardioprotection was
      blocked by atractyloside (n = 7 per group). CONCLUSIONS: Inhibition of GSK or p53
      lowers the threshold of helium-induced preconditioning via a mPTP-dependent
      mechanism in vivo.

PMID- 18713883
TI  - The efficacy of aprotinin in arterial switch operations in infants.
AB  - BACKGROUND: In the present study we assessed whether aprotinin at a total dose
      (40,000 kallikrein inhibitor units (KIU)/kg) is effective in reducing
      postoperative blood loss and blood product requirement after arterial switch
      operations in infants. METHODS: A prospective, double-blind, randomized study,
      evaluated 50 infants who underwent arterial switch operations for transposition
      of great arteries. Patients were randomized into a placebo group, 25 patients who
      received normal saline and a treatment group, 25 patients who received 20,000
      KIU/kg of aprotinin after induction of anesthesia, followed by 20,000 KIU/kg of
      aprotinin added to pump prime. Postoperative blood loss through the thoracic
      chest tubes and blood product requirements (mL/kg/24 h) were measured for the
      first 24 h in the intensive care unit. RESULTS: Postoperative blood loss in the
      first 24 h was significantly (P < 0.0001) higher in the placebo group (49.7 +/-
      11.9 mL/kg/24 h) as compared to the aprotinin group (37.1 +/- 3.5 mL/kg/24 h).
      Requirements for fresh frozen plasma (mL/kg/24 h) and use of platelet concentrate
      transfusion (mL/kg/24 h) were significantly less in patients who received
      aprotinin (P < 0.0001), but did not reduce the proportion of patients transfused
      with blood products. The number of total donor exposures to all allogenic blood
      products was less in the aprotinin group [range (median) = 2-4 (3)] than the
      placebo group [range (median) = 7-14 (10)]. The re-exploration for excessive
      bleeding was significantly less with aprotinin group (16% vs 32%) (P = 0.01).
      CONCLUSION: Our study concludes that aprotinin decreased the postoperative blood
      loss and requirement of transfusion of fresh frozen plasma and platelets
      (mL/kg/24 h) during the early postoperative period. Further, it reduced the
      number of donor exposures and re-exploration for excessive bleeding in the
      treatment population.

PMID- 18713884
TI  - Incidental finding of superior vena cava mass missed on transesophageal
      echocardiography but seen on epiaortic imaging.

PMID- 18713885
TI  - Transesophageal echocardiography in a patient in hemodynamic compromise after
      Jarvik 2000 implantation: the suckdown effect.

PMID- 18713886
TI  - Near-infrared spectroscopy: an important monitoring tool during hybrid aortic
      arch replacement.
AB  - Near-infrared spectroscopy can be helpful for monitoring the adequacy of cerebral
      perfusion during cardiovascular surgery. We report changes seen in regional
      oxygen saturation due to intraoperative thrombosis of the left common carotid
      artery graft during hybrid aortic arch replacement for traumatic aortic injury.

PMID- 18713887
TI  - Somatosensory evoked potentials by median nerve stimulation in children during
      thiopental/sevoflurane anesthesia and the additive effects of ketoprofen and
      fentanyl.
AB  - BACKGROUND: Somatosensory evoked potentials (SEPs) are used to determine the
      spinal cord and brain function during surgical procedures. In general, SEPs are
      sensitive to volatile anesthetics, but little is known about the effects of
      anesthesia maintenance with sevoflurane on SEPs in children. Analgesics are often
      provided during anesthesia, and supplementary drugs may also affect the SEPs. In
      this prospective clinical trial of 27 healthy, 3- to 8-yr-old children, we
      evaluated the effects of sevoflurane anesthesia after IV induction with
      benzodiazepine and barbiturate on median nerve SEP. In addition, the effects of
      two analgesics (ketoprofen and fentanyl) on SEPs were evaluated. METHODS: Median
      nerve SEPs were recorded before premedication with midazolam 0.1 mg/kg IV, and at
      three separate times during anesthesia maintenance with sevoflurane 2% end-tidal
      concentration in air/oxygen (after 15 min of sevoflurane inhalation),
      supplemented with/without ketoprofen 1 mg/kg (after 25 min) and fentanyl 1
      microg/kg (after 35 min). RESULTS: Compared with baseline measurements, an
      increase both in N20 latency (P = 0.015) and in central conduction time (P =
      0.001) was noted during anesthesia maintenance with sevoflurane. The
      administration of analgesics did not have an influence on the N20 latency or
      central conduction time. In children 5 to 8 yr of age, the mean cortical N20-P25
      amplitude was decreased (P = 0.008). In addition, in older children, the N20-P25
      amplitude decreased after the co-administration of ketoprofen and fentanyl
      compared with the values measured before the analgesics (P = 0.03). These
      decreases were not seen in the younger children. DISCUSSION: In children,
      anesthesia maintenance with 2% sevoflurane prolongs median SEP latencies in a
      manner that is similar to those reported for other volatile anesthetics. However,
      SEP monitoring can be done with sevoflurane inhalation, but the dosage should be
      adjusted due to interindividual variability. Co-administration of ketoprofen, and
      fentanyl did not affect the SEP latencies, but post hoc analysis suggested that
      older children had a decrease in cortical amplitudes.

PMID- 18713888
TI  - The effect of propofol concentration on dispersion of myocardial repolarization
      in children.
AB  - BACKGROUND: QT interval prolongation on the electrocardiogram (ECG) may be drug
      induced and is traditionally associated with torsades des pointes. A better
      predictor of torsades des pointes is the time interval between the peak and the
      end of the T-wave (Tp-e). Older studies of propofol's effect on the corrected
      interval (QTc) are conflicting and confounded by polypharmacy. It was recently
      shown that target-controlled infusion of propofol at 3 microg/mL has no effect on
      QTc or Tp-e. This plasma concentration of propofol is at the extreme lower end of
      the range for surgical anesthesia. In this randomized, double-blind, clinical
      study, we investigated the dose-response relationship between propofol, QTc, and
      Tp-e in a range of doses clinically relevant for surgical anesthesia. METHODS:
      Sixty healthy unpremedicated children, aged 3-10 yr, were recruited. Subjects
      were randomized to receive target-controlled infusions of propofol, to achieve 1
      of 3 plasma concentrations: 3, 4.5, and 6 microg/mL. A preoperative 12 lead ECG
      was performed and repeated 5 min after induction. Two investigators, blinded to
      group allocation and to the timing of the ECG traces, independently measured QTc
      and Tp-e within and between each group. Paired t-tests were used to compare QTc
      and Tp-e within groups. One-way analysis of variance was used for intergroup
      analysis. The primary outcome measure was a change of >25 ms in Tp-e both within
      and between groups. RESULTS: ECG recordings were obtained in 51 children. There
      were no demographic or ECG differences at baseline, at which time QTc and Tp-e
      values were within normal limits. There were no differences in QTc or Tp-e after
      induction within or between the three different groups. DISCUSSION: Propofol has
      no effect on myocardial repolarization in healthy children at clinically relevant
      doses. This suggests that propofol would be a rational choice for children with a
      preexisting repolarization abnormality.

PMID- 18713889
TI  - Extra-1 acupressure for children undergoing anesthesia.
AB  - BACKGROUND: Acupuncture and related techniques have been used as adjuncts for
      perioperative anesthesia management. We examined whether acupressure in the Extra
      1 (Yin-Tang) point would result in decreased preprocedural anxiety and reduced
      intraprocedural propofol requirements in a group of children undergoing
      endoscopic procedures. METHODS: Fifty-two children were randomized to receive
      acupressure bead intervention either at the Extra-1 acupuncture point or at a
      sham point. A Bispectral Index (BIS) monitor was applied to all children before
      the onset of the intervention. Anxiety was assessed at baseline and before
      entrance to the operating room. Anesthetic techniques were standardized and
      maintained with IV propofol infusion titrated to keep BIS values of 40-60.
      RESULTS: We found that after the intervention, children in the Extra-1 group
      experienced reduced anxiety whereas children in the sham group experienced
      increased anxiety (-9% [-3 to -15] vs 2% [-6 to 7.4], P = 0.012). In contrast, no
      significant changes in BIS values were observed in the preprocedural waiting
      period between groups (P = ns). We also found that total intraprocedural propofol
      requirements did not differ between the two study groups (214 +/- 76 microg x kg(
      1) x min(-1) vs 229 +/- 95 microg x kg(-1) x min(-1), P = 0.52). CONCLUSIONS: We
      conclude that acupressure bead intervention at Extra-1 acupoint reduces
      preprocedural anxiety in children undergoing endoscopic procedures. This
      intervention, however, has no impact on BIS values or intraprocedural propofol
      requirements.

PMID- 18713890
TI  - The dose-response of nitrous oxide in postoperative nausea in patients undergoing
      gynecologic laparoscopic surgery: a preliminary study.
AB  - BACKGROUND: Whether nitrous oxide (N(2)O) increases the incidence of
      postoperative nausea and vomiting (PONV) after laparoscopic gynecologic surgery
      is still controversial, which may be due to the administration of different
      concentrations of inspired N(2)O. We investigated whether N(2)O results in a dose
      response increase in PONV. METHODS: Patients undergoing gynecologic laparoscopic
      surgery were randomized to receive 30% oxygen with air (G0, n = 46), 50% N(2)O
      with oxygen (G50, n = 46), or 70% N(2)O with oxygen (G70, n = 45). A standardized
      general anesthetic was used with no PONV prophylaxis. Known risk factors for PONV
      were controlled. Metoclopramide was used as a rescue antiemetic. The incidence of
      nausea, vomiting, use of rescue antiemetic, and pain visual analog scale (VAS)
      score was measured at 2 and 24 h postoperatively. RESULTS: Patient demographics
      were comparable, and there were no differences among groups regarding factors
      that may influence PONV. The incidence of PONV at 24 h was 33% (15 of 46) in the
      G0 group, 46% (21 of 46) in the G50 group, and 62% (28 of 45) in the G70 group (P
      = 0.018). Subgroup analysis revealed a difference between G0 versus G70 groups (P
      = 0.018), but no significant difference between G0 versus G50 groups and G50
      versus G70 groups. The incidence of nausea showed a similar difference (G0 = 26%,
      G50 = 35%, and G70 = 56%; P = 0.012), but the incidence of vomiting was not
      different among the groups although there was a trend (G0 = 28%, G50 = 35%, and
      G70 = 42%; P = 0.377). The severity of nausea (measured by VAS 100 mm) was
      significantly increased with increasing N(2)O concentration (G0 = 10.9, G50 =
      12.7, and G70 = 20.5; P = 0.027). The highest VAS score during 24 h was used for
      the analysis. There was no difference in the use of a rescue antiemetic among
      groups. Pain VAS scores and opioids consumption were not different among groups
      (at 2 and 24 h after surgery). CONCLUSIONS: N(2)O increases the incidence of
      postoperative nausea after gynecologic laparoscopic surgery. This preliminary
      finding indicates that N(2)O may increase PONV in a dose-dependent fashion. A
      study with a sample size of >400 patients in each group would be necessary to
      demonstrate a statistically significant difference among each of these three
      groups. We do not recommend using a high concentration of N(2)O in this clinical
      setting.

PMID- 18713891
TI  - The duration of intrathecal bupivacaine mixed with lidocaine.
AB  - BACKGROUND: Although spinal bupivacaine may have too long duration to be useful
      in the ambulatory setting, recent animal data suggest that lidocaine added to
      spinal bupivacaine may reduce the duration of bupivacaine spinal anesthesia. We
      explored whether lidocaine added to spinal bupivacaine could shorten the duration
      of bupivacaine spinal anesthesia in humans similarly to what has been reported in
      animals. METHODS: Ninety patients presenting for transurethral resection of
      bladder tumor or prostate were assigned to one of three groups by double blind
      randomization to receive intrathecal 1.5 mL of hyperbaric 0.5% bupivacaine, plus
      0.6 mL of one of three solutions: saline (Group I, n = 30, control), 1% lidocaine
      (Group II, n = 30), and 2% lidocaine (Group III, n = 30). Peak sensory block
      level, time to peak sensory block, times to two-segment, L1, and S2 regressions
      from peak sensory block, motor blocks at peak sensory block, L1, and S2
      regressions, and postanesthesia care unit stay time (PACU time) were measured.
      RESULTS: Times to peak sensory block were similar in all three groups. Times to
      two-segment, L1, and S2 regressions from peak sensory block, and PACU time were
      significantly reduced in Group II compared to Group I. Times to L1, S2
      regressions, and PACU times in Group III were significantly prolonged.
      CONCLUSIONS: We conclude that lidocaine (6 mg) mixed to spinal bupivacaine (7.5
      mg) can shorten the duration of bupivacaine spinal anesthesia, therefore provide
      more rapid recovery from the spinal anesthesia compared to the same dose of
      bupivacaine (7.5 mg) alone.

PMID- 18713894
TI  - Genetics and the evolution of the anesthetic response.

PMID- 18713893
TI  - A hypothesis on the origin and evolution of the response to inhaled anesthetics.
AB  - In this article, I present an evolutionary explanation for why organisms respond
      to inhaled anesthetics. It is conjectured that organisms today respond to inhaled
      anesthetics owing to the sensitivity of ion channels to inhaled anesthetics,
      which in turn has arisen by common descent from ancestral, anesthetic-sensitive
      ion channels in one-celled organisms (i.e., that the response to anesthetics did
      not arise as an adaptation of the nervous system, but rather of ion channels that
      preceded the origin of multicellularity). This sensitivity may have been refined
      by continuing selection at synapses in multicellular organisms. In particular, it
      is hypothesized that 1) the beneficial trait that was selected for in one-celled
      organisms was the coordinated response of ion channels to compounds that were
      present in the environment, which influenced the conformational equilibrium of
      ion channels; 2) this coordinated response prevented the deleterious consequences
      of entry of positive charges into the cell, thereby increasing the fitness of the
      organism; and 3) these compounds (which may have included organic anions,
      cations, and zwitterions as well as uncharged compounds) mimicked inhaled
      anesthetics in that they were interfacially active, and modulated ion channel
      function by altering bilayer properties coupled to channel function. The proposed
      hypothesis is consistent with known properties of inhaled anesthetics. In
      addition, it leads to testable experimental predictions of nonvolatile compounds
      having anesthetic-like modulatory effects on ion channels and in animals,
      including endogenous compounds that may modulate ion channel function in health
      and disease. The latter included metabolites that are increased in some types of
      end-stage organ failure, and genetic metabolic diseases. Several of these
      predictions have been tested and proved to be correct.

PMID- 18713895
TI  - Why can all of biology be anesthetized?

PMID- 18713892
TI  - Is a new paradigm needed to explain how inhaled anesthetics produce immobility?
AB  - A paradox arises from present information concerning the mechanism(s) by which
      inhaled anesthetics produce immobility in the face of noxious stimulation.
      Several findings, such as additivity, suggest a common site at which inhaled
      anesthetics act to produce immobility. However, two decades of focused
      investigation have not identified a ligand- or voltage-gated channel that alone
      is sufficient to mediate immobility. Indeed, most putative targets provide
      minimal or no mediation. For example, opioid, 5-HT3, gamma-aminobutyric acid type
      A and glutamate receptors, and potassium and calcium channels appear to be
      irrelevant or play only minor roles. Furthermore, no combination of actions on
      ligand- or voltage-gated channels seems sufficient. A few plausible targets
      (e.g., sodium channels) merit further study, but there remains the possibility
      that immobilization results from a nonspecific mechanism.

PMID- 18713896
TI  - Does natural selection explain the universal response of metazoans to volatile
      anesthetics?

PMID- 18713897
TI  - Meyer and Overton revisited.

PMID- 18713898
TI  - Anesthetic-like modulation of receptor function by surfactants: a test of the
      interfacial theory of anesthesia.
AB  - INTRODUCTION: Inhaled anesthetics are interfacially active, concentrating at
      interfaces such as the protein/water or bilayer/water interfaces. We tested the
      hypothesis that interfacial activity was a sufficient condition for anesthetic
      like modulation of receptor function by applying surfactants to gamma
      aminobutyric acid type A (GABA(A)), glycine, and N-methyl-d-aspartate (NMDA)
      receptors. We defined anesthetic-like modulation as an increase in currents
      through native channels that isoflurane and ethanol increased currents through,
      and a decrease in currents through channels that isoflurane and ethanol decreased
      currents through. We also tested the null hypothesis that there would be no
      difference in modulation of channel currents by surfactants in receptors with
      point mutations that diminished their response to isoflurane and ethanol compared
      to the native version of these receptors. METHODS: The effect of seven
      surfactants with different head group charges (anionic, cationic, zwitterionic,
      and uncharged) and tail lengths (8 carbons and 12 carbons) on homomeric wild type
      alpha1 and mutant alpha(1) (S267I) glycine receptors, wild type
      alpha(1)beta(2)gamma(2s) and mutant alpha(1)(S270I)beta(2)gamma(2s) GABA(A)
      receptors, and wild type NR1/NR2A and mutant NR1(F639A)/NR2A NMDA receptors was
      studied. Receptors were expressed in Xenopus laevis oocytes and studied using two
      electrode voltage clamping. RESULTS: All seven surfactants, isoflurane, and
      ethanol enhanced GABA(A) receptor function. Six of seven surfactants, isoflurane,
      and ethanol enhanced glycine receptor function. Six of seven surfactants,
      isoflurane, and ethanol inhibited NMDA receptor function. For the mutant
      receptors, five of seven surfactants increased currents through GABA(A)
      receptors, whereas six of seven surfactants increased currents through glycine
      receptors. Six of seven surfactants decreased currents through the NMDA receptor.
      In contrast to isoflurane and ethanol, surfactants as a group did not diminish
      modulation of mutant compared to wild type receptors. CONCLUSION: These findings
      identify another large class of compounds (surfactants) that modulate the
      function of GABA(A), glycine, and NMDA receptors in a manner that is
      qualitatively similar to inhaled anesthetics. We cannot reject the hypothesis
      that interfacial activity is a sufficient condition for anesthetic-like
      modulation of these receptors. Mutations that diminish the modulatory effect of
      isoflurane and ethanol did not diminish the modulatory effect of the surfactants.

PMID- 18713899
TI  - Intrathecal veratridine administration increases minimum alveolar concentration
      in rats.
AB  - BACKGROUND: Results from several studies point to sodium channels as potential
      mediators of the immobility produced by inhaled anesthetics. We hypothesized that
      the intrathecal administration of veratridine, a drug that enhances the activity
      or effect of sodium channels, should increase MAC. METHODS: We measured the
      change in isoflurane MAC caused by intrathecal infusion of various concentrations
      of veratridine into the lumbothoracic subarachnoid space of rats. We compared
      these result with those obtained from intracerebroventricular infusion. RESULTS:
      As predicted, intrathecal infusion of veratridine increased MAC. The greatest
      infused concentration (25 microM) also produced neuronal injury in the hindlimbs
      of two rats and decreased the peak effect on MAC. A concentration of 1.6 microM
      produced the largest (21%) increase in MAC. Intraventricular infusion of 1.6 and
      6.4 microM veratridine did not alter MAC. Rats given 25 microM died. CONCLUSIONS:
      Intrathecal administration of veratradine increases MAC of isoflurane, a finding
      consistent with a role for sodium channels as potential mediators of the
      immobility produced by inhaled anesthetics.

PMID- 18713901
TI  - Isoflurane prevents nicotine-evoked norepinephrine release from the mouse spinal
      cord at low clinical concentrations.
AB  - BACKGROUND: Volatile anesthetics inhibit nicotinic acetylcholine receptors at
      subanesthetic concentrations. In both animal and human studies, similar
      concentrations of volatile anesthetics have been associated with increased
      sensitivity to pain. Nicotinic analgesia is thought to involve the enhanced
      release of norepinephrine. These studies are intended as a "proof of concept"
      that alteration of the nicotinic facilitation of norepinephrine release is a
      potential mechanism for isoflurane-induced pronociception. METHODS: We conducted
      our study using a murine lumbar spinal cord slice model. We evoked norepinephrine
      release with nicotine in the presence and absence of isoflurane. To identify the
      type of nicotinic receptor involved, we studied the effect of receptor and
      subtype-specific ligands and genetically engineered mice, which lacked the gene
      expression for the nicotinic beta2 subunit. The amount of [(3)H]-norepinephrine
      released was measured under the different conditions. RESULTS: Nicotine
      facilitated norepinephrine release was significantly and maximally inhibited by
      isoflurane at concentrations that enhance pain sensitivity in vivo (0.38%).
      Facilitation of norepinephrine release was mimicked by the alpha 7 selective
      agonist choline and inhibited in the presence of alpha-bungarotoxin, an alpha 7
      nicotinic selective antagonist. Facilitation of norepinephrine release was not
      different in animals lacking beta2 subunits compared with matched controls.
      CONCLUSIONS: Nicotinic facilitation of norepinephrine release in the spinal cord
      is inhibited by isoflurane at low clinically relevant concentrations. Because the
      net effect of noradrenergic tone in the spinal cord is inhibitory, the removal of
      this mechanism might be responsible for the enhanced pain sensitivity seen at
      these concentrations of isoflurane.

PMID- 18713902
TI  - Infrared measurement of carbon dioxide in the human breath: "breathe-through"
      devices from Tyndall to the present day.
AB  - The ability to measure carbon dioxide (CO(2)) in the breath of a patient or
      capnometry, is one of the fundamental technological advances of modern medicine.
      I will chronicle the evolution and commercialization of mainstream capnometry
      based upon infrared measurement of CO(2) in the breath using information from the
      historical record and personal interviews with many of the developers.

PMID- 18713900
TI  - Increases in spinal cerebrospinal fluid potassium concentration do not increase
      isoflurane minimum alveolar concentration in rats.
AB  - BACKGROUND: Previous studies demonstrated that MAC for isoflurane directly
      correlates with the concentration of Na(+) in cerebrospinal fluid surrounding the
      spinal cord, the primary site for mediation of the immobility produced by inhaled
      anesthetics. If this correlation resulted from increased irritability of the
      cord, then infusion of increased concentrations of potassium (K(+)) might be
      predicted to act similarly. However, an absence of effect of K(+) might be
      interpreted to indicate that K(+) channels do not mediate the immobility produced
      by inhaled anesthetics whereas Na(+) channels remain as potential mediators.
      Accordingly, in the present study, we examined the effect of altering intrathecal
      concentrations of K(+) on MAC. METHODS: In rats prepared with chronic indwelling
      intrathecal catheters, we infused solutions deficient in K(+) and with an excess
      of K(+) into the lumbar space and measured MAC for isoflurane 24 h before,
      during, and 24 h after infusion. Rats similarly prepared were tested for the
      effect of altered osmolarity on MAC (accomplished by infusion of mannitol) and
      for the penetration of Na(+) into the cord. RESULTS: MAC of isoflurane never
      significantly increased with increasing concentrations of K(+) infused
      intrathecally. At infused concentrations exceeding 12 times the normal
      concentration of KCl, i.e., 29 mEq/L, rats moved spontaneously at isoflurane
      concentrations just below, and sometimes at MAC, but the average MAC in these
      rats did not exceed their control MAC. At the largest infused concentration (58.1
      mEq/L), MAC significantly decreased and did not subsequently return to normal
      (i.e., such large concentrations produced injury). Infusions of lower
      concentrations of K(+) had no effect on MAC. Infusion of osmotically equivalent
      solutions of mannitol did not affect MAC. Na(+) infused intrathecally measurably
      penetrated the spinal cord. CONCLUSIONS: The results do not support a mediation
      or modulation of MAC by K(+) channels.

PMID- 18713903
TI  - A pilot study of neonatal and pediatric esophageal pulse oximetry.
AB  - BACKGROUND: In this pilot study we explored the suitability of the esophagus as a
      new measuring site for blood oxygen saturation (Spo(2)) in neonates. METHODS: A
      new miniaturized esophageal pulse oximeter has been developed. Five patients (one
      child and four neonates) were studied. RESULTS: Spo(2) values were obtained in
      the esophagus of all patients. A Bland and Altman plot of the difference between
      Spo(2) values from the esophageal pulse oximeter and a commercial toe pulse
      oximeter against their mean showed that the bias and the limits of agreement
      between the two pulse oximeters were +0.3% and +1.7% to -1.0%, respectively.
      CONCLUSIONS: This study suggests that the esophagus can be used as an alternative
      site for monitoring blood oxygen saturation in children and neonates.

PMID- 18713904
TI  - An in-vivo metabolic test for detecting malignant hyperthermia susceptibility in
      humans: a pilot study.
AB  - INTRODUCTION: In vitro contracture testing to diagnose malignant hyperthermia
      (MH) susceptibility requires a muscle biopsy, which may be associated with severe
      side effects for the patient. After investigation of several different protocols,
      we present a less invasive metabolic test that involves IM injection of caffeine
      and halothane, and subsequent measurement of interstitial lactate to
      differentiate between MH susceptible (MHS) and MH non-susceptible (MHN)
      individuals. METHODS: Two microdialysis probes with attached microtubing for
      trigger injection were inserted into the lateral vastus muscle of eight
      previously diagnosed MHS patients (representing three genetic variants
      Gly2434Arg, Thr2206Met, and Arg614Cys), seven MHN patients, and seven control
      individuals. After equilibration and lactate baseline recording, a single bolus
      of 200 muL caffeine 80 mM and a suspension of 200 muL halothane 4%V/V in soy bean
      oil (triggers) were injected locally. Lactate was measured
      spectrophotometrically. Data are presented as medians and interquartile ranges.
      RESULTS: Although baseline lactate values were similar in the investigated groups
      before trigger injection, caffeine increased local lactate in MHS patients
      significantly more (2.0 [1.8-2.6] mM) than in MHN (0.8 [0.6-1.1] mM) or in
      control individuals (0.8 [0.6-0.8 mM]). Similarly, halothane lead to a
      significant lactate increase in MHS compared to MHN and control individuals (8.6
      [3.7-8.9] mM vs 0.9 [0.5-1.1] mM and 1.7 [0.9-2.3] mM, respectively). However, a
      relevant increase of lactate was observed in one MHN and in two control
      individuals. Systemic hemodynamic and metabolic variables did not differ between
      the investigated groups. DISCUSSION: Metabolic monitoring of IM lactate after
      local caffeine and halothane injection may allow less invasive testing to detect
      MH susceptibility, without systemic side effects.

PMID- 18713905
TI  - Patients with difficult intubation may need referral to sleep clinics.
AB  - PURPOSE: Upper airway abnormalities carry the risk of obstructive sleep apnea
      (OSA) and difficult tracheal intubations. Both conditions contribute to
      significant clinical problems and have increased perioperative morbidity and
      mortality. We hypothesized that patients who presented with difficult intubation
      would have a very high prevalence of OSA and that those with unexpected difficult
      intubation may require referral to sleep clinics for polysomnography (PSG).
      METHODS: Patients classified as a grade 4 Cormack and Lehane on direct
      laryngoscopic view, and who required more than two attempts for successful
      endotracheal intubation, were referred to the study by consultant
      anesthesiologists at four hospitals. Apnea-hypopnea index (AHI) data and
      postoperative events were collected. Patients with AHI >5/h were considered
      positive for OSA. Clinical and PSG variables were compared using t-tests and
      chi(2) test. RESULTS: Over a 20-mo period, 84 patients with a difficult
      intubation were referred into the study. Thirty-three patients agreed to
      participate. Sixty-six percent (22 of 33) had OSA (AHI >5/h). Of the 22 OSA
      patients, 10 patients (64%) had mild OSA (AHI 5-15), 6 (18%) had moderate OSA
      (AHI >15/h), and 6 (18%) had severe OSA (AHI >30/h). Of the 33 patients, 11
      patients (33%) were recommended for continuous positive airway pressure
      treatment. Between the OSA group and the non-OSA group, there were significant
      differences in gender, neck size, and the quality of sleep, but there were no
      significant differences in age and body mass index. CONCLUSIONS: Sixty-six
      percent of patients with unexpected difficult intubation who consented to undergo
      a sleep study were diagnosed with OSA by PSG. Patients with difficult intubation
      are at high risk for OSA and should be screened for signs and symptoms of sleep
      apnea. Screening for OSA should be considered by referral to a sleep clinic for
      PSG.

PMID- 18713906
TI  - Transurethral resection syndrome detected and managed using transesophageal
      Doppler.
AB  - Transurethral resection syndrome during transurethral resection of the prostate
      (TURP) results from excessive absorption of electrolyte-free irrigation fluids
      causing acute hypervolemia and hyponatremia. Neuraxial anesthesia is often
      recommended for TURP procedures because early signs of neurological deterioration
      can be detected. However, in patients requiring general anesthesia, other
      continuous and noninvasive measures are needed. Acute intravascular hypervolemia
      should be reflected by changes in hemodynamic values. Transesophageal Doppler
      ultrasonography of the aorta allows determination of stroke volume and other
      advanced hemodynamic variables related to intravascular volume status. We
      describe the first case of intraoperative detection of a TURP syndrome by
      noninvasive Doppler monitoring of hemodynamic variables during TURP.

PMID- 18713907
TI  - Respiratory depression with tramadol in a patient with renal impairment and
      CYP2D6 gene duplication.
AB  - We observed opioid-related respiratory depression in a patient receiving tramadol
      via patient-controlled analgesia. Predisposing factors were the patient's genetic
      background and renal impairment. Complete recovery occurred after naloxone
      administration, thus confirming opioid intoxication. Analysis of the patient's
      genotype revealed a CYP2D6 gene duplication resulting in ultra-rapid metabolism
      of tramadol to its active metabolite (+)O-desmethyltramadol. Concomitant renal
      impairment resulting in decreased metabolite clearance enhanced opioid toxicity.
      This genetic CYP2D6 variant is particularly common in specific ethnic populations
      and should be a future diagnostic target whenever administration of tramadol or
      codeine is anticipated, as both drugs are subject to a comparable CYP2D6
      dependent metabolism.

PMID- 18713908
TI  - Determinants of tidal volumes with adaptive support ventilation: a multicenter
      observational study.
AB  - INTRODUCTION: In the present study, we investigated the behavior of adaptive
      support ventilation (ASV) in patients after cardiothoracic surgery. We determined
      tidal volumes (Vt) and factors that influence Vt with this mode of microprocessor
      controlled mechanical ventilation (MV). METHODS: This was a prospective,
      multicenter, observational study in three Dutch intensive care units over a 5-mo
      period. MV data were collected during steady-state after arrival in the intensive
      care unit. RESULTS: Data were collected for 346 consecutive patients after
      cardiothoracic surgery: 262 patients weaned with ASV, and 84 patients weaned with
      pressure-controlled/pressure-support MV. With ASV the mean (+/- sd) Vt expressed
      per kilogram actual body weight was 7.1 +/- 1.6 mL. Expressed per kilogram ideal
      body weight (IBW), Vt was 8.3 +/- 1.5 mL. In patients with a correctly set body
      weight (SBW) (i.e., the IBW), Vt was 8.1 +/- 1.4 mL/kg. With pressure
      controlled/pressure-support-MV Vt was 7.3 +/- 1.4 mL/kg IBW (P < 0.001 vs ASV).
      Multivariate logistic regression analysis showed Vt with ASV to be dependent on
      only two parameters: respiratory rate and the correctness of SBW. CONCLUSIONS: Vt
      with ASV seems to be dependent on two parameters: respiratory rate and the
      correctness of SBW. The first factor is not clinically important because
      respiratory rate is automatically chosen by the microprocessor. The second factor
      is clinically important because it is the only factor that can be influenced by
      the operator. Our data show the importance of setting the correct weight with
      ASV. With ASV, Vt are >8 mL/kg IBW in a substantial number of patients.
      Randomized clinical trials should be performed to compare ASV with other
      ventilation modes.

PMID- 18713909
TI  - Adaptive support ventilation with percutaneous dilatational tracheotomy: a
      clinical study.
AB  - We determined the need for changes in minute ventilation with adaptive support
      ventilation after percutaneous dilatational tracheotomy under endoscopic guidance
      in 34 intensive care unit patients. During the procedure, minute ventilation was
      not changed; only maximum pressure limits were adjusted, if necessary. After
      insertion of the tracheotomy, cannula minute ventilation was adjusted only if
      Paco(2)-values changed >or=0.5 kPa from baseline. In 74% of patients, adaptive
      support ventilation was unable to maintain minute ventilation during the use of
      the endoscope, mandating pressure limitation adjustments. In a minority of
      patients (26%), minute ventilation had to be adjusted to achieve similar Paco(2)
      values.

PMID- 18713910
TI  - Functional residual capacity changes after different endotracheal suctioning
      methods.
AB  - BACKGROUND: Our primary objective was to investigate the effects of three
      different endotracheal suctioning procedures on functional residual capacity
      (FRC). METHODS: Using a crossover design, postoperative cardiac surgery patients
      (n = 20) received three different suctioning methods in randomized order: closed
      suctioning during pressure-controlled ventilation, closed suctioning during
      volume-controlled ventilation, and open suctioning. FRC was measured before and
      20 min after the intervention. RESULTS AND CONCLUSIONS: FRC is reduced in
      postcardiac surgery patients after suctioning, regardless of which method is
      used. Certain patients may have very pronounced changes of FRC. Routine FRC
      measurements could complement respiratory monitoring to optimize respiratory
      therapy.

PMID- 18713911
TI  - Acute pulmonary artery embolism during transcatheter embolization: successful
      resuscitation with veno-arterial extracorporeal membrane oxygenation.
AB  - Versatile particles from transcatheter embolization may accidentally enter the
      pulmonary circulation, causing severe pulmonary embolism. A 36-yr-old woman
      patient suffering from an arteriovenous malformation in the left shoulder
      underwent embolization with micro coils, N-butyl-2-cyanoacrylate/lipiodol and
      polyvinyl alcohol particles. During embolization, acute onset of tachycardia,
      hypotension, and decline in oxygen saturation indicated right ventricular failure
      and decreased pulmonary perfusion confirmed by angiography. As mechanical
      resuscitation failed to stabilize cardiocirculatory function, veno-arterial
      extracorporeal membrane oxygenation support was preformed until hemodynamic
      stability was regained. Extracorporeal membrane oxygenation should be considered
      for cases where pulmonary embolism causes right ventricular failure and
      circulatory arrest during transcatheter embolization.

PMID- 18713912
TI  - An evaluation of the postoperative antihyperalgesic and analgesic effects of
      intrathecal clonidine administered during elective cesarean delivery.
AB  - BACKGROUND: Intrathecal clonidine improves intraoperative anesthesia and
      postoperative analgesia after cesarean delivery. Clonidine also possesses
      antihyperalgesic properties. Hyperalgesia contributes to postoperative pain and
      may be associated with increased risk of chronic pain after surgery. In this
      study, we evaluated the postoperative antihyperalgesic effect of intrathecal
      clonidine after caesarean delivery. METHODS: Ninety-six parturients undergoing
      elective cesarean delivery were randomly assigned to receive intrathecal
      bupivacaine-sufentanil (BS group), bupivacaine-sufentanil-clonidine 75 microg
      (BSC group), or bupivacaine-clonidine 150 microg (BC group). The primary outcome
      was the extent and the incidence of periincisional punctate mechanical
      hyperalgesia as assessed by response to application of a von Frey filament at 24
      and 48 h after cesarean delivery. Postoperative morphine requirements and pain
      scores, as well as residual pain at 1, 3, and 6 mo, were also assessed. RESULTS:
      The BC group had a significantly reduced area of periincisional hyperalgesia at
      48 h (median, 25th-75th percentiles): 1.0 (1.0 - 3.3) cm(2) vs 9.5 (5.0-14.0)
      cm(2) in the BS group vs 5.0 (2.5-12.3) cm(2) in the BSC group (P = 0.02 with the
      BS group). The incidence of hyperalgesia at 48 h was also lower in the BC group:
      16% vs 41% in the BS group vs 34% in the BSC group (P = 0.03 with BS group).
      Postoperative morphine consumption, pain scores, and incidence and intensity of
      residual pain did not differ among groups. CONCLUSIONS: Intrathecal clonidine 150
      mug combined with bupivacaine had a postoperative antihyperalgesic effect
      expressed as a significant reduction in the extent and incidence of
      periincisional punctate mechanical hyperalgesia at 48 h after elective cesarean
      delivery compared with intrathecal bupivacaine-sufentanil and intrathecal
      clonidine 75 mug-bupivacaine-sufentanil.

PMID- 18713913
TI  - Respiratory depression after neuraxial opioids in the obstetric setting.
AB  - Neuraxial opioids have contributed significantly to improved labor and
      postcesarean delivery analgesia. In the obstetric population, epidural and
      intrathecal opioids are associated with a very low risk of clinically significant
      respiratory depression. Although rare, respiratory depression is a serious risk;
      patients may die or suffer permanent brain damage as a consequence. This review
      discusses the mechanism and incidence, as well as the prevention, detection, and
      management of respiratory depression with morphine, extended-release epidural
      morphine, and lipophilic opioids in the labor and cesarean delivery setting.

PMID- 18713914
TI  - Successful placement of a right ventricular assist device for treatment of a
      presumed amniotic fluid embolism.
AB  - Amniotic fluid embolism is a rare and often fatal complication of pregnancy. We
      report the successful multidisciplinary management of a woman who developed a
      coagulopathy from a presumed amniotic fluid embolism after forceps-assisted
      vaginal delivery requiring recombinant factor VIIa, and pulmonary arterial
      hypertension requiring a right ventricular assist device.

PMID- 18713915
TI  - Automated correction of room location errors in anesthesia information management
      systems.
AB  - BACKGROUND: Anesthesia information management systems (AIMS) and operating room
      information management systems (ORIMS) are both used in operating rooms (OR).
      Anesthesia providers use AIMS to document their care in near real-time, including
      milestone events, and these systems automatically record vital signs from patient
      monitors. Circulating nurses use ORIMS primarily to document procedural
      information. Because of automatic documentation, AIMS would be ideal platforms
      for OR managerial decision support if the correct locations of cases in progress
      were known accurately. Trust is diminished if recommendations are poor. METHODS:
      We compiled room location error rates from prior analyses of ORIMS data. Data
      from 24 consecutive 4-wk periods (45,459 cases) were analyzed from one hospital
      where both ORIMS and AIMS data were available. The actual location of cases was
      inferred from the physical location of the workstation recording the majority of
      pulse oximetry saturations. These were compared to the listed location in the
      AIMS and the final corrected location in the ORIMS. The scheduled and final ORIMS
      locations were compared to determine how often location changes were updated
      before the start of anesthesia. The location of cases was inferred in near real
      time by using the identifier of the AIMS workstation transmitting pulse oximetry
      saturated electrocardiogram heart rate, and end-tidal CO(2) partial pressures.
      RESULTS: Location error rates ranged from 0% to 7.5% at 42 hospitals. The error
      rate at the studied hospital was just 0.4%, showing that the hospital was
      suitable for investigation. The 0.4% error rate was based on cases listed as
      overlapping in the same OR, and thus under-estimated the actual error rate in the
      ORIMS (1.0%). With education, there was a decrease in the moved cases in the
      ORIMS whose location was not changed before the start of anesthesia (9.3%-2.0%, P
      < 10(-5)). Despite the significant improvement (P < 10(-5)) in the error rate
      between the AIMS listed and actual locations, the residual AIMS real-time error
      rate was 4.1% of cases. Use of vital sign data reduced errors to <0.1%.
      CONCLUSIONS: Education can only modestly improve the accuracy of OR locations in
      ORIMS and AIMS data. The actual location can be inferred, either in near real
      time or afterwards, from the AIMS workstation transmitting vital sign data. This
      addresses the fundamental problem of cases having more than one location during
      the course of anesthetic care (e.g., holding area, block room, OR, and
      postanesthesia care unit), which cannot be determined from scheduled ORIMS or
      listed AIMS locations.

PMID- 18713916
TI  - Clinicians consistently exceed a typical person's short-term memory during
      preoperative teaching.
AB  - INTRODUCTION: Patient education is a critical part of preparation for surgery.
      Little research on provider-to-patient teaching has been conducted with
      systematic focus on the quantity of information provided to patients. This is
      important to assess because short-term memory capacity for information such as
      preoperative instruction is limited to roughly seven units of content. METHODS:
      We studied the information-giving practices of anesthesiologists and nurse
      practitioners during preoperative teaching by examining transcripts from 26 tape
      recorded preoperative evaluation appointments. We developed a novel coding system
      to measure: 1) quantity of information, 2) frequency of medical terminology, 3)
      number of patient questions, and 4) number of memory reinforcements used during
      the consultation. Results are reported as mean +/- sd. RESULTS: Anesthesiologists
      and nurse practitioners vastly exceeded patients' short-term memory capacity.
      Nurse practitioners gave significantly more information to patients than did
      physicians (112 +/- 37 vs 49 +/- 25 items per interview, P < 0.01). This higher
      level of information-giving was not influenced by the question-asking behaviors
      of the patients. Nurse practitioners and physicians used similar numbers of
      medical terms (4.0 +/- 2.4 vs 3.7 +/- 2.8 explained terms per interview), and
      memory-supporting reinforcements (2.3 +/- 3.0 vs 1.4 +/- 2.0 reinforcements per
      interview). DISCUSSION: Given the known limits of short-term memory, clinicians
      would be well advised to carefully consider their patterns of information-giving
      and their use of memory-reinforcing strategies for critical information.

PMID- 18713917
TI  - Cerebral perfusion pressure in neurotrauma: a review.
AB  - It is now well recognized that low cerebral blood flow (and cerebral perfusion
      pressure (CPP)) is associated with poor outcome after traumatic brain injury.
      What is less clear is whether altering cerebral blood flow or CPP will lead to
      clinical improvement. Initial studies indicated that increasing CPP may be
      beneficial and the Brain Trauma Foundation acknowledged this by incorporating a
      target of 70 mm Hg in the 1996 guidelines. However, the lack of a demonstrable
      benefit and the increased complication rate associated with this approach led to
      a reduction in the CPP goal to 60 mm Hg. More recently, evidence that
      autoregulation may be disrupted after traumatic brain injury has led some authors
      to propose an individualized approach to CPP management. Furthermore, with the
      advent of advanced neuromonitoring techniques, clinicians are able to more
      closely monitor the effects of hemodynamic manipulations on cerebral metabolism.
      As yet, there is no strong outcome evidence to support this approach. Until then,
      the current debate over the optimal approach to CPP management is likely to
      continue.

PMID- 18713918
TI  - Lengthening of the trachea during neck extension: which part of the trachea is
      stretched?
AB  - BACKGROUND: We sought to determine the distances of the three segments of the
      airway from upper incisors to carina in intubated patients in three different
      neck positions. METHODS: Twenty patients undergoing elective surgery were
      studied. The airway was divided into three segments: upper incisor to vocal cords
      (UI-VC), vocal cords to sternal notch (VC-SN), and sternal notch to the carina
      (SN-CA). After general anesthesia and tracheal tube placement, the circuit was
      connected and the lungs ventilated. A bronchoscope was inserted through a ported
      elbow adapter until the tip just contacted carina. A marker tape was placed on
      the bronchoscope immediately above the adapter port. As the bronchoscope was
      withdrawn to the sternal notch (by transillumination), vocal cords and upper
      incisor (endoscopic visualization), three corresponding markers were placed along
      the bronchoscope. The three segments of the airway were obtained by measuring the
      distances between the four markers. Measurements were taken with the patient's
      neck in flexion (10 cm pillow), neutral (5 cm pillow), and extension (no pillow)
      positions. Repeated measure analysis of variance and paired t-tests were used for
      analysis of the data. RESULTS: The UI-VC, VC-SN, and SN-CA distances were 12.01
      +/- 1.49, 5.37 +/- 0.95, 8.24 +/- 1.16 cm. From neck flexion to extension, UI-VC
      and VC-SN increased by 0.36 +/- 0.68 cm (P = 0.027) and 1.74 +/- 0.48 cm (P <
      0.001) respectively; SN-CA decreased by 0.12 +/- 0.70 cm (NS). Overall, UI-CA
      increased by 1.99 +/- 0.70 cm (P < 0.001). SN-CA represented 64%, 61%, 56% of the
      VC-CA distance with the neck in flexion, neutral, and extension respectively. SN
      CA did not change significantly among the head positions (NS). CONCLUSIONS: From
      neck flexion to extension, the UI-CA distance increased by 1.99 cm. The major
      contribution to this lengthening was an increase of the VC-SN distance by 1.74
      cm; UI-VC increased by 0.36 cm whereas SN-CA did not change significantly.
      Averaging the three neck positions, SN-CA represented 60% of the VC-CA distance.
      Our findings may explain why tracheal tubes fixed at the mouth ascend in the
      trachea with neck extension.

PMID- 18713919
TI  - A comparison of a silicone wire-reinforced tube with the Parker and polyvinyl
      chloride tubes for tracheal intubation through an intubating laryngeal mask
      airway in patients with normal airways undergoing general anesthesia.
AB  - BACKGROUND: The intubating laryngeal mask airway (ILMA) is used in the management
      of difficult intubation. Usually, a silicone wire-reinforced tube is inserted for
      tracheal intubation. Because the silicone wire-reinforced tube is expensive,
      alternatives, such as polyvinyl chloride (PVC) and posterior beveled Parker
      tubes, are worth considering. We compared the blind intubation success rates
      among the silicone wire-reinforced tube, the Parker tube, and the PVC tube, and
      identified laryngeal structures preventing tracheal intubations through the ILMA.
      METHODS: Sixty-three adult patients were randomized into three groups: Group I (n
      = 20) silicone wire-reinforced tube, Group II (n = 21) Parker tube, and Group III
      (n = 22) PVC tube. Demographic and clinical continuous data were compared with
      the analysis of variance with the Scheffe test for post hoc analysis. Frequencies
      and percentages were compared with the chi(2) test. RESULTS: Tracheal intubation
      was successful from the first attempt in 18 of 20 patients in Group I (silicone
      wire-reinforced tube), which was significantly higher than the success rate in
      either Group II (12 of 22 patients) (Parker tube) or Group III (10 of 21
      patients) (PVC tube). With clockwise or anticlockwise rotation of the tracheal
      tube, the number of successful intubations did not change in Group I, but it
      increased to 19 of 22 patients in Group II and to 12 of 21 patients in Group III.
      The rate of successful intubation between patients in Group I (90%) and Group II
      (86%) was not significantly different after manipulation of the tracheal tube (P
      = 0.72). However, the rate of successful tracheal intubations in patients of
      Group III (57%) was significantly lower in comparison to patients in both Group I
      (P = 0.02) and Group II (P = 0.03). In 3 of the 22 patients of Group II and in 9
      of the 21 patients of Group III in whom blind intubation was not possible, the
      obstruction was due to the epiglottis tubercule. CONCLUSIONS: Manipulation
      improved the success rate of intubation with the Parker tube through the ILMA
      rendering it a possible alternative to the silicone wire-reinforced tube.

PMID- 18713920
TI  - Transdermal nicotine for analgesia after radical retropubic prostatectomy.
AB  - BACKGROUND: Previous animal and human studies suggested that nicotine might have
      an antinociceptive effect. We hypothesized that the preoperative application of a
      7 mg nicotine patch would result in reduced postoperative analgesic requirements
      in patients undergoing radical retropubic prostatectomy (RRP) under general
      anesthesia. METHODS: Nonsmokers undergoing RRP under general anesthesia were
      enrolled in this prospective, double-blind, placebo-controlled study. Patients
      were randomly assigned to receive a patch of 7 mg nicotine or placebo applied
      behind the ear 30-60 min before induction of anesthesia. The anesthetic technique
      was standardized. Postoperative analgesia was provided with a standardized
      morphine patient-controlled analgesia and 6 hourly ketorolac 15 mg IV. Data were
      collected in the postanesthesia care unit and at 6, 12, and 24 h after surgery.
      RESULTS: Ninety patients were included in the analysis: 44 in the nicotine group
      and 46 in the placebo group. The groups did not differ significantly with respect
      to age, height, weight, ASA class, length of surgery, or amounts of
      intraoperative fentanyl received. The nicotine group showed significantly lower
      cumulative morphine consumption at 24 h (mean +/- sd): 33.3 +/- 30.8 mg vs 44.7
      +/- 26.4 mg (P = 0.0059, time x treatment P = 0.0031). However, the repeated
      measures tests found no difference in amount of pain reported on coughing or at
      rest, either as treatment effects or in interaction with time. In post hoc
      comparisons, there was no significant difference in amount of pain reported on
      coughing or at rest at any of the times assessed. There were also no significant
      differences between the groups in the incidence of postoperative nausea and
      vomiting or the need for rescue antiemetics. However, the maximum nausea verbal
      rating scale score was higher in the nicotine than in the placebo group (median,
      25th to 75th percentiles = 4, 0-6 vs 0, 0-6, P = 0.0158). There was a significant
      negative correlation between the 24 h plasma nicotine levels and postoperative
      morphine consumption in the postanesthesia care unit (P = 0.049), as well as at
      6, 12, and 24 h (P = 0.002). CONCLUSION: The preoperative application of a 7 mg
      nicotine patch resulted in a significant reduction in opioid consumption in
      patients undergoing RRP under general anesthesia. Despite this reduction in
      opioid use, there was no reduction in pain scores or postoperative nausea and
      vomiting with the use of transdermal nicotine.

PMID- 18713921
TI  - Transdermal nicotine patch for postoperative pain management: a pilot dose
      ranging study.
AB  - BACKGROUND: Nicotine has been shown to be antinociceptive in the postoperative
      period in animal studies. Human studies with nasal nicotine sprays have had mixed
      results, possibly due to variability in pharmacokinetics and potential patient
      variables such as exposure to nicotine in tobacco smokers. In this pilot study,
      we examined the analgesic effect of a transdermal nicotine patch applied before
      surgery in nonsmokers. METHODS: We conducted a randomized, double-blind,
      prospective placebo-controlled trial of 40 subjects, undergoing general surgery
      that required postoperative patient-controlled analgesia and an overnight
      hospital admission. Immediately before surgery, a transdermal nicotine patch
      containing 0, 5, 10, or 15 mg was applied. The primary outcome variable was pain
      report using a numerical rating scale (NRS) in the first hour after surgery and
      over the next 5 days. Secondary outcomes were pain medication use, hemodynamic
      values, nausea, and sedation. RESULTS: Patients treated with nicotine reported
      lower pain scores when compared with those treated with placebo during the first
      hour after surgery (P = 0.003, average NRS decrease = 1.4, 95% CI = 0.3-2.6) and
      for 5 days after surgery (P = 0.03, average NRS decrease = 1.0, 95% CI = 0.1
      1.9). There was no increased benefit of nicotine with doses larger than 5 mg.
      There was a trend suggesting decreased pain medicine use, increased nausea,
      decreased tachycardia, and slightly decreased systolic blood pressure in the
      nicotine groups, but these values did not reach significance. CONCLUSIONS:
      Transdermal nicotine, 5-15 mg, reduced postoperative pain scores but failed to
      decrease the need for opioid analgesics or opioid-related side effects after
      general surgical procedures.

PMID- 18713922
TI  - Transdermal nicotine patch failed to improve postoperative pain management.
AB  - BACKGROUND: A single 3 mg intranasal dose of nicotine has been reported to have
      analgesic properties. We designed placebo-controlled study to test the hypothesis
      that transdermal nicotine (TDN) administered over a 3-day period would decrease
      postoperative pain and opioid analgesic usage and improve the recovery process
      after lower abdominal surgery. METHODS: Ninety-seven patients undergoing
      abdominal hysterectomy procedures were randomly assigned to one of two treatment
      groups: (1) control group received inert (sham) patches 1 h before and for 2 days
      after surgery, or the (2) nicotine group received TDN 30 (21 mg nicotine) patches
      1 h before induction of anesthesia and for two additional days after surgery. The
      anesthetic technique was identical in both groups, and the postoperative
      assessments included verbal rating scales for pain and sedation, IV patient
      controlled analgesia morphine usage, quality of recovery assessment, recovery of
      bowel function, resumption of normal activities, and patient satisfaction with
      their pain management. Follow-up evaluations were performed at 1 and 3 mo after
      the operation to assess late recovery events. RESULTS: Postoperative patient
      controlled analgesia morphine usage and pain scores while supine or sitting up,
      intraoperative fentanyl use, oral analgesic consumption, return of bowel sounds,
      and passage of flatus did not differ between the two groups. Although ambulation
      and hospitalization times, as well as quality of recovery scores, did not differ,
      resumption of oral intake was delayed in the nicotine group. Discharge
      eligibility scores were higher in the nicotine group at 48 and 72 h compared with
      the control group, but the time to return to work was 19 days in both treatment
      groups. CONCLUSIONS: Perioperative administration of a high-dose TDN patch did
      not improve postoperative pain control or decrease the analgesic requirement
      after pelvic gynecological surgery. Despite delayed resumption of oral intake,
      more patients in the nicotine group were ready for discharge at 48 and 72 h after
      surgery. However, times to resuming activities of daily living were similar in
      both groups.

PMID- 18713923
TI  - The impact of blood pressure and baroreflex sensitivity on wind-up.
AB  - BACKGROUND: Elevated resting blood pressure (BP) and spontaneous baroreflex
      sensitivity (BRS) are associated with hypoalgesia to acute pain. These
      associations are significantly altered in chronic pain. We investigated whether
      degree of wind-up (marker for central sensitization) is similarly influenced by
      BP and BRS, and whether these associations are altered by chronic pain. METHODS:
      BP and BRS (sequence method) were assessed in 30 healthy and 26 chronic back pain
      subjects who then completed a standardized thermal stimulation protocol to assess
      wind-up. This protocol was performed under placebo and alpha-2 adrenergic (ADRA2)
      blockade with yohimbine in counterbalanced order to test for the influence of
      ADRA2 mechanisms. RESULTS: 1) In healthy controls, higher systolic BP was
      associated with lower wind-up (P < 0.05) but this was reversed in chronic pain
      subjects (P < 0.05); 2) higher BRS was associated with lower wind-up in healthy
      controls (P < 0.05) but not in the chronic pain group; 3) higher systolic BP was
      associated with lower BRS only in the chronic pain group (P < 0.05); and 4) ADRA2
      receptor blockade did not significantly affect wind-up. CONCLUSIONS: These
      findings suggest that hypoalgesia associated with elevated resting BP and BRS in
      healthy individuals involves both diminished central sensitization (reflected in
      wind-up) and enhanced descending inhibition. The presence of chronic pain
      significantly alters the nature of these interactions. The reversal of normal
      interactions between overlapping systems modulating cardiovascular systems and
      pain in chronic pain patients may shift the healthy buffering of BP and heart
      rate toward instability and eventual higher BP and cardiovascular morbidity.

PMID- 18713925
TI  - Retraction. Inhibition of the HERG channel by droperidol depends on channel
      gating and involves the S6 residue F656. Anesth Analg 2008;106:1161-70.

PMID- 18713924
TI  - A systematic review of randomized trials evaluating regional techniques for
      postthoracotomy analgesia.
AB  - BACKGROUND: Thoracotomy induces severe postoperative pain and impairment of
      pulmonary function, and therefore regional analgesia has been intensively studied
      in this procedure. Thoracic epidural analgesia is commonly considered the "gold
      standard" in this setting; however, evaluation of the evidence is needed to
      assess the comparative benefits of alternative techniques, guide clinical
      practice and identify areas requiring further research. METHODS: In this
      systematic review of randomized trials we evaluated thoracic epidural,
      paravertebral, intrathecal, intercostal, and interpleural analgesic techniques,
      compared to each other and to systemic opioid analgesia, in adult thoracotomy.
      Postoperative pain, analgesic use, and complications were analyzed. RESULTS:
      Continuous paravertebral block was as effective as thoracic epidural analgesia
      with local anesthetic (LA) but was associated with a reduced incidence of
      hypotension. Paravertebral block reduced the incidence of pulmonary complications
      compared with systemic analgesia, whereas thoracic epidural analgesia did not.
      Thoracic epidural analgesia was superior to intrathecal and intercostal
      techniques, although these were superior to systemic analgesia; interpleural
      analgesia was inadequate. CONCLUSIONS: Either thoracic epidural analgesia with LA
      plus opioid or continuous paravertebral block with LA can be recommended. Where
      these techniques are not possible, or are contraindicated, intrathecal opioid or
      intercostal nerve block are recommended despite insufficient duration of
      analgesia, which requires the use of supplementary systemic analgesia.
      Quantitative meta-analyses were limited by heterogeneity in study design, and
      subject numbers were small. Further well designed studies are required to
      investigate the optimum components of the epidural solution and to rigorously
      evaluate the risks/benefits of continuous infusion paravertebral and intercostal
      techniques compared with thoracic epidural analgesia.

PMID- 18713926
TI  - Continuous low-dose ketamine improves the analgesic effects of fentanyl patient
      controlled analgesia after cervical spine surgery.
AB  - BACKGROUND: The effects of fentanyl with ketamine for postoperative pain are
      unknown. We investigated the adjuvant effects of ketamine for fentanyl patient
      controlled analgesia. METHODS: Cervical and lumbar spine surgery patients were
      divided into three groups: ketamine 1 mg/kg followed by 42 and 83 microg x kg(-1)
      x h(-1) in ketamine-1 and ketamine-2 group, respectively, and a control group.
      Postoperative patient-controlled analgesia fentanyl was administered with a
      background infusion. RESULTS: Pain scores and analgesia requirement in the
      ketamine-2 group were significantly lower than those of the control group after
      cervical surgery. Ketamine partially improved the analgesic effects of fentanyl
      after lumbar surgery. CONCLUSION: Small-dose ketamine improved the analgesic
      effects of fentanyl after cervical surgery.

PMID- 18713927
TI  - Restoration of calcium influx corrects membrane hyperexcitability in injured rat
      dorsal root ganglion neurons.
AB  - BACKGROUND: We have previously shown that a decrease of inward Ca(2+) flux
      (I(Ca)) across the sensory neuron plasmalemma, such as happens after axotomy,
      increases neuronal excitability. From this, we predicted that increasing I(Ca) in
      injured neurons should correct their hyperexcitability. METHODS: The influence of
      increased or decreased I(Ca) upon membrane biophysical variables and excitability
      was determined during recording from A-type neurons in nondissociated dorsal root
      ganglia after spinal nerve ligation using an intracellular recording technique.
      RESULTS: When the bath Ca(2+) level was increased to promote I(Ca), the after
      hyperpolarization was decreased and repetitive firing was suppressed, which also
      followed amplification of Ca(2+)-activated K(+) current with selective agents
      NS1619 and NS309. A decreased external bath Ca(2+) concentration had the opposite
      effects, similar to previous observations in uninjured neurons. CONCLUSIONS:
      These findings indicate that at least a part of the hyperexcitability of somatic
      sensory neurons after axotomy is attributable to diminished inward Ca(2+) flux,
      and that measures to restore I(Ca) may potentially be therapeutic for painful
      peripheral neuropathy.

PMID- 18713928
TI  - The antinociceptive response to nicotinic agonists in a mouse model of
      postoperative pain.
AB  - BACKGROUND: Nicotine, the prototypical broad spectrum agonist at central
      nicotinic receptors, has analgesic action after surgery. Various subtype-specific
      nicotinic agonists have antinociceptive effects in animal models, but the
      response is highly dependent on the model tested. In an effort to determine what
      nicotinic subtypes might be targeted in future clinical studies, we tested
      agonists selective for alpha 4 beta 2 and alpha 7 containing nicotinic receptors
      in a mouse model of postoperative pain. METHODS: After paw incision, mice were
      tested for heat latency and pressure threshold before and after treatment with a
      dose range of ligands selective for alpha 4 beta 2 and alpha 7 containing
      nicotinic receptors. To demonstrate that nicotine reduced nociceptive input in
      this model, the lumbar spinal cords of a subgroup of these mice were stained for
      the phosphorylated form if CREB. RESULTS: Nicotine and metanicotine (alpha 4 beta
      2 selective) were fully effective as an analgesic in heat and pressure testing.
      The alpha 7 partial agonist GTS-21 significantly increased the heat latency after
      surgery, but did not alter pressure threshold. The alpha 7 selective antagonist
      methyllicaconitine decreased the efficacy of nicotine to increase heat latency
      but did not affect pressure threshold. The number of cells in the superficial
      dorsal horn with nuclei that stained for pCREB was double on the surgical side
      and the ratio was reduced by nicotine in a dose-dependent manner. CONCLUSIONS:
      Our findings suggest that nicotine reduced nociceptive input to the superficial
      and deep dorsal horn. It also provides support for alpha 4 beta 2 and alpha 7
      nicotinic-mediated antinociceptive actions.

PMID- 18713929
TI  - Pre-Irradiation of blood by gallium aluminum arsenide (830 nm) low-level laser
      enhances peripheral endogenous opioid analgesia in rats.
AB  - BACKGROUND: Low-level laser therapy (LLLT) has been reported to relieve pain,
      free of side effects. However, the mechanisms underlying LLLT are not well
      understood. Recent studies have also demonstrated that opioid-containing immune
      cells migrate to inflamed sites and release beta-endorphins to inhibit pain as a
      mode of peripheral endogenous opioid analgesia. We investigated whether pre
      irradiation of blood by LLLT enhances peripheral endogenous opioid analgesia.
      METHODS: The effect of LLLT pretreatment of blood on peripheral endogenous opioid
      analgesia was evaluated in a rat model of inflammation. Additionally, the effect
      of LLLT on opioid production was also investigated in vitro in rat blood cells.
      The expression of the beta-endorphin precursors, proopiomelanocortin and
      corticotrophin releasing factor, were investigated by reverse transcription
      polymerase chain reaction. RESULTS: LLLT pretreatment produced an analgesic
      effect in inflamed peripheral tissue, which was transiently antagonized by
      naloxone. Correspondingly, beta-endorphin precursor mRNA expression increased
      with LLLT, both in vivo and in vitro. CONCLUSION: These findings suggest that
      that LLLT pretreatment of blood induces analgesia in rats by enhancing peripheral
      endogenous opioid production, in addition to previously reported mechanisms.

PMID- 18713930
TI  - The antiallodynic effect of Neurotropin is mediated via activation of descending
      pain inhibitory systems in rats with spinal nerve ligation.
AB  - BACKGROUND: Neurotropin, a nonprotein extract isolated from inflamed skin of
      rabbits inoculated with vaccinia virus, is widely used in Japan to treat chronic
      pain such as neuropathic pain. Although some studies have been conducted on the
      mechanism of the antiallodynic action of Neurotropin, this mechanism has yet to
      be adequately clarified. METHODS: The left fifth lumbar nerve of rats was tightly
      ligated with silk sutures under pentobarbital anesthesia. Mechanical allodynia
      was confirmed by measuring the hindpaw withdrawal threshold in response to
      application of von Frey filaments. Behavioral tests were performed at 28 days
      after nerve ligation. Neurotropin was administered IV, intrathecally or
      intracerebroventricularly in L5 spinal nerve ligation (L5-SNL) rats. We examined
      the effects of noradrenergic, serotonergic and gamma-aminobutyric acid
      (GABA)ergic antagonists on the antiallodynic action of Neurotropin in L5-SNL
      rats. Yohimbine hydrochloride (yohimbine) was used as an alpha(2) adrenoceptor
      antagonist, ketanserin tartrate (ketanserin) as a 5-HT(2A) receptor antagonist,
      MDL72,222 as a 5-HT(3) receptor antagonist, (-)-bicuculline methobromide
      (bicuculline) as a GABA(A) receptor antagonist, and CGP35,348 as a GABA(B)
      receptor antagonist, and intrathecally injected. RESULTS: IV (50-100 NU/kg) doses
      of Neurotropin elicited an antiallodynic action in L5-SNL rats. Moreover,
      intracerebroventricular (400 mNU/rat), but not intrathecal, injection of
      Neurotropin inhibited allodynia. The antiallodynic action of Neurotropin (100
      NU/kg, IV) was antagonized by intrathecal injections of yohimbine (10 nmol/rat),
      ketanserin (30 nmol/rat), MDL72,222(30 nmol/rat), bicuculline (0.6 nmol/rat) and
      CGP35348 (30 nmol/rat). On the other hand, the antiallodynic action of
      intrathecally injected m-CPBG (5-HT(3) receptor agonist) was reversed by
      intrathecal injection of bicuculline and CGP35348, suggesting interaction of 5
      HT(3) receptors and spinal inhibitory (GABAergic) interneurons. CONCLUSIONS:
      These results suggest that the antiallodynic effect of Neurotropin is mediated
      via activation of descending pain inhibitory systems, such as the noradrenergic
      and serotonergic systems, which project from supraspinal sites to the spinal
      dorsal horn. In addition, activation of inhibitory GABAergic interneurons via 5
      HT(3) receptors by serotonin released in the spinal dorsal horn may also be
      involved in the antiallodynic action of Neurotropin.

PMID- 18713931
TI  - Ultrasound imaging accurately identifies the lateral femoral cutaneous nerve.
AB  - BACKGROUND: Anesthesia of the lateral femoral cutaneous nerve (LFCN) is useful in
      surgery involving the anterolateral thigh. We investigated the accuracy of
      ultrasound compared with anatomical landmarks in identifying the LFCN in human
      cadavers and volunteers. METHODS: Twenty cadavers were examined. A needle was
      inserted targeting the LFCN with ultrasound guidance and green dye was injected.
      A second needle was inserted using anatomical landmarks. The LFCN was identified
      by dissection, and coloring of the LFCN and needle positions were evaluated. A
      volunteer study with 10 individuals was performed. Transdermal nerve stimulation
      was used to identify the LFCN bilaterally. Its position was compared with marked
      positions identified in advance using ultrasound and anatomical landmarks.
      RESULTS: Sixteen of 19 needles inserted under ultrasound guidance in the cadavers
      were in contact with the LFCN. The median horizontal distance from the needle tip
      to the nerve was 0.0 mm (interquartile range [IQR], 0.0-0.0 mm). Only 1 of 19
      needles inserted using anatomical landmarks was in contact with the LFCN. The
      median horizontal distance from the needle tip to the nerve was 18.0 mm (IQR,
      11.0-23.0 mm). Sixteen of 20 marked positions made using ultrasound guidance
      corresponded to the identified LFCN in volunteers. The median horizontal distance
      from the pen-mark to the LFCN was 0.0 mm (IQR, 0.0-0.0 mm). None of the 20 marked
      positions made with anatomical landmarks corresponded to the LFCN. The median
      horizontal distance from the pen-mark to the LFCN was 15.0 mm (IQR, 10.8-20.0
      mm). CONCLUSIONS: Identification of the LFCN by ultrasound is technically
      feasible and more accurate than anatomical landmarks.

PMID- 18713932
TI  - A comparison between ultrasound-guided infraclavicular block using the "double
      bubble" sign and neurostimulation-guided axillary block.
AB  - BACKGROUND: Ultrasound-guided infraclavicular block can be performed using the
      double bubble sign. Previously described, the double bubble sign consists
      superiorly of the axillary artery (in short axis) superimposed on an inferior
      bubble created by local anesthetic injection. In this study, we compared this new
      method of brachial plexus anesthesia to the traditional triple-nerve stimulation
      axillary block. METHODS: Seventy patients were randomized to receive a single
      injection, ultrasound-guided infraclavicular block using the double bubble sign
      or a triple-stimulation axillary block. RESULTS: Both methods produced similar
      success rates (89%-91%). However, infraclavicular blocks were associated with a
      shorter performance time (3.90 +/- 2.27 vs 8.03 +/- 3.92 min; P < 0.001) and
      lower block-related pain scores (2.70 +/- 2.02 vs 4.17 +/- 2.57 on a 0-10 scale;
      P = 0.01). CONCLUSION: Compared to triple-stimulation axillary block, ultrasound
      guided infraclavicular block using the double bubble sign provided a similar
      efficacy, a shorter performance time and lower procedural pain scores.

PMID- 18713933
TI  - Epidural multiorifice catheters function as single-orifice catheters: an in vitro
      study.
AB  - In an in vitro study, we determined the flow rates required to use selective
      orifices of multiorifice catheters. Saline was infused at rates between 1 and 360
      mL/h through Portex and Braun 20-gauge multiorifice catheters using Baxter,
      Abbott Laboratories, and Alaris infusion pumps. The numbers of orifices used via
      infusion and manual injection, and the pressure within the catheter during
      continuous infusion, were recorded. Infusion rates <80 mL/h used one orifice,
      between 100 and 280 mL/h used two orifices, and >300 mL/h used three orifices.
      Catheter pressures with Braun catheters were 40% greater than with Portex
      catheters. Manual injections by all 12 residents used all three orifices. Twenty
      gauge multiorifice catheters function as single-orifice catheters at clinically
      relevant infusion rates, but function as multiorifice catheters during manual
      boluses.

PMID- 18713934
TI  - Frequency-dependent block in humans?

PMID- 18713935
TI  - Re: Undersizing left double-lumen tubes.

PMID- 18713936
TI  - Pharyngeal morbidity and the high intracuff pressure of classic laryngeal mask
      airway.

PMID- 18713937
TI  - A recommended solution for avoiding coring of a rubber stopper.

PMID- 18713938
TI  - Difficult Removal of an Arrow FlexTip Plus epidural catheter.

PMID- 18713939
TI  - Air penetration into the tissues during oral surgery.

PMID- 18713940
TI  - Another use of an orthopedic tourniquet.

PMID- 18713941
TI  - The drain tube of ProSeal laryngeal mask airway can be used as a basic monitor.

PMID- 18713942
TI  - Problems and solutions arising during a study in visual semantics of the medical
      emergency team system.
AB  - A study of the medical emergency team (MET) to explore communication within the
      team, leadership, handover, and MET resuscitation practice was performed using
      audiovisual recording in hospitals of Sydney South West Area Health Service,
      Sydney, Australia. In this article, we report on the process of data collection:
      the completion of 25 video recordings of MET calls across three of the six study
      hospitals. We describe how we gained entry into hospital environments to film
      events characterized by the unpredictability and uncertainties associated with
      resuscitating a patient and the strategies that we implemented during the
      fieldwork to develop and maintain rapport with both clinicians and managers. We
      describe how we addressed some of the practical constraints related to collecting
      audiovisual data at the point of acute care as well as their implications for the
      theoretical and methodological aspects of the study.

PMID- 18713943
TI  - Effect of extracellular fluid volume on single-sample measurement of glomerular
      filtration rate.
AB  - Objective. The objective of our study was to evaluate the effect of extracellular
      fluid volume (ECV) on the accuracy of measurement of glomerular filtration rate
      from a single sample (GFR1). METHODS: Multi-sample GFR (GFR6) and ECV (per 1.73
      m(2)) were measured with both Cr-51-EDTA and iohexol, injected into opposite arms
      (110 studies in 80 subjects). Six plasma samples were obtained bilaterally 20-
      240 min post-injection to measure GFR6/1.73 m(2). GFR1/1.73 m(2) was calculated
      from 2-, 3- and 4-h samples using Jacobsson's formula for iohexol and the
      Christensen and Groth formula for Cr-51-EDTA. The quotient, GFR1/GFR6, was taken
      to indicate the accuracy of GFR1. RESULTS: When GFR6 was <60 ml/min/1.73 m(2),
      GFR1/ GFR6 correlated positively with ECV at all single-sample times. When GFR6
      was 60-90 ml/min/1.73 m(2) or >90 ml/min/1.73 m(2), GFR1/GFR6 correlated
      positively with ECV at 2 h, but negatively at 4 h, indicating that at some time
      between 2 and 4 h, GFR1/GFR6 was transiently independent of ECV. A plot of the
      regression gradient of GFR1/GFR6 on ECV against sample time indicated that the
      time of transient independence, at which time GFR1 depends exclusively on GFR6,
      was 3.2-3.9 h (depending on indicator combination used) when GFR6 was 60-90
      ml/min/1.73 m(2) and 2.4-2.9 h when GFR was >90 ml/min/1.73 m(2). Transient
      independence when GFR6 was <60 ml/min/1.73 m(2) was not reached by 4 h and
      estimated to be 5-7 h. CONCLUSION: The accuracy of GFR1 depends on ECV,
      overestimation or underestimation respectively depending on sample time and GFR.
      The time at which GFR1 is independent of ECV increases with decreasing GFR. If
      sampling time is too early, GFR1 overestimates GFR, but the reverse occurs when
      sampling is too late, even if GFR is abnormally low.

PMID- 18713944
TI  - Broad influenza-specific CD8+ T-cell responses in humanized mice vaccinated with
      influenza virus vaccines.
AB  - The development of novel human vaccines would be greatly facilitated by the
      development of in vivo models that permit preclinical analysis of human immune
      responses. Here, we show that nonobese diabetic severe combined immunodeficiency
      (NOD/SCID) beta(2) microglobulin(-/-) mice, engrafted with human CD34+
      hematopoietic progenitors and further reconstituted with T cells, can mount
      specific immune responses against influenza virus vaccines. Live attenuated
      trivalent influenza virus vaccine induces expansion of CD8+ T cells specific to
      influenza matrix protein (FluM1) and nonstructural protein 1 in blood, spleen,
      and lungs. On ex vivo exposure to influenza antigens, antigen-specific CD8+ T
      cells produce IFN-gamma and express cell-surface CD107a. FluM1-specific CD8+ T
      cells can be also expanded in mice vaccinated with inactivated trivalent
      influenza virus vaccine. Expansion of antigen-specific CD8+ T cells is dependent
      on reconstitution of the human myeloid compartment. Thus, this humanized mouse
      model permits preclinical testing of vaccines designed to induce cellular
      immunity, including those against influenza virus. Furthermore, this work sets
      the stage for systematic analysis of the in vivo functions of human DCs. This, in
      turn, will allow a new approach to the rational design and preclinical testing of
      vaccines that cannot be tested in human volunteers.

PMID- 18713945
TI  - Thalidomide and rituximab in Waldenstrom macroglobulinemia.
AB  - Thalidomide enhances rituximab-mediated, antibody-dependent, cell-mediated
      cytotoxicity. We therefore conducted a phase 2 study using thalidomide and
      rituximab in symptomatic Waldenstrom macroglobulinemia (WM) patients naive to
      either agent. Intended therapy consisted of daily thalidomide (200 mg for 2
      weeks, then 400 mg for 50 weeks) and rituximab (375 mg/m(2) per week) dosed on
      weeks 2 to 5 and 13 to 16. Twenty-five patients were enrolled, 20 of whom were
      untreated. Responses were complete response (n = 1), partial response (n = 15),
      and major response (n = 2), for overall and major response rate of 72% and 64%,
      respectively, on an intent-to-treat basis. Median serum IgM decreased from 3670
      to 1590 mg/dL (P < .001), whereas median hematocrit rose from 33.0% to 37.6% (P =
      .004) at best response. Median time to progression for responders was 38 months.
      Peripheral neuropathy to thalidomide was the most common adverse event. Among 11
      patients experiencing grade 2 or greater neuropathy, 10 resolved to grade 1 or
      less at a median of 6.7 months. Thalidomide in combination with rituximab is
      active and produces long-term responses in WM. Lower doses of thalidomide (ie,
      <or= 200 mg/day) should be considered given the high frequency of treatment
      related neuropathy in this patient population. This trial is registered at
      www.clinicaltrials.gov as #NCT00142116.

PMID- 18713946
TI  - MYC stimulates EZH2 expression by repression of its negative regulator miR-26a.
AB  - The MYC oncogene, which is commonly mutated/amplified in tumors, represents an
      important regulator of cell growth because of its ability to induce both
      proliferation and apoptosis. Recent evidence links MYC to altered miRNA
      expression, thereby suggesting that MYC-regulated miRNAs might contribute to
      tumorigenesis. To further analyze the impact of MYC-regulated miRNAs, we
      investigated a murine lymphoma model harboring the MYC transgene in a Tet-off
      system to control its expression. Microarray-based miRNA expression profiling
      revealed both known and novel MYC targets. Among the miRNAs repressed by MYC, we
      identified the potential tumor suppressor miR-26a, which possessed the ability to
      attenuate proliferation in MYC-dependent cells. Interestingly, miR-26a was also
      found to be deregulated in primary human Burkitt lymphoma samples, thereby
      probably being of clinical relevance. Although today only few miRNA targets have
      been identified in human disease, we could show that ectopic expression of miR
      26a influenced cell cycle progression by targeting the bona fide oncogene EZH2, a
      Polycomb protein and global regulator of gene expression yet unknown to be
      regulated by miRNAs. Thus, in addition to directly targeting protein-coding
      genes, MYC modulates genes important to oncogenesis via deregulation of miRNAs,
      thereby vitally contributing to MYC-induced lymphomagenesis.

PMID- 18713947
TI  - IRF-4 functions as a tumor suppressor in early B-cell development.
AB  - Interferon regulatory factor-4 (IRF-4) is a hematopoietic cell-restricted
      transcription factor important for hematopoietic development and immune response
      regulation. It was also originally identified as the product of a proto-oncogene
      involved in chromosomal translocations in multiple myeloma. In contrast to its
      oncogenic function in late stages of B lymphopoiesis, expression of IRF-4 is down
      regulated in certain myeloid and early B-lymphoid malignancies. In this study, we
      found that the IRF-4 protein levels are increased in lymphoblastic cells
      transformed by the BCR/ABL oncogene in response to BCR/ABL tyrosine kinase
      inhibitor imatinib. We further found that IRF-4 deficiency enhances BCR/ABL
      transformation of B-lymphoid progenitors in vitro and accelerates disease
      progression of BCR/ABL-induced acute B-lymphoblastic leukemia (B-ALL) in mice,
      whereas forced expression of IRF-4 potently suppresses BCR/ABL transformation of
      B-lymphoid progenitors in vitro and BCR/ABL-induced B-ALL in vivo. Further
      analysis showed that IRF-4 inhibits growth of BCR/ABL+ B lymphoblasts primarily
      through negative regulation of cell-cycle progression. These results demonstrate
      that IRF-4 functions as tumor suppressor in early B-cell development and may
      allow elucidation of new molecular pathways significant to the lymphoid
      leukemogenesis by BCR/ABL. The context dependent roles of IRF-4 in oncogenesis
      should be an important consideration in developing cancer therapies targeting IRF
      4.

PMID- 18713948
TI  - Biologic properties and enucleation of red blood cells from human embryonic stem
      cells.
AB  - Human erythropoiesis is a complex multistep process that involves the
      differentiation of early erythroid progenitors to mature erythrocytes. Here we
      show that it is feasible to differentiate and mature human embryonic stem cells
      (hESCs) into functional oxygen-carrying erythrocytes on a large scale (10(10)
      10(11) cells/6-well plate hESCs). We also show for the first time that the oxygen
      equilibrium curves of the hESC-derived cells are comparable with normal red blood
      cells and respond to changes in pH and 2,3-diphosphoglyerate. Although these
      cells mainly expressed fetal and embryonic globins, they also possessed the
      capacity to express the adult beta-globin chain on further maturation in vitro.
      Polymerase chain reaction and globin chain specific immunofluorescent analysis
      showed that the cells increased expression of beta-globin (from 0% to > 16%)
      after in vitro culture. Importantly, the cells underwent multiple maturation
      events, including a progressive decrease in size, increase in glycophorin A
      expression, and chromatin and nuclear condensation. This process resulted in
      extrusion of the pycnotic nuclei in up to more than 60% of the cells generating
      red blood cells with a diameter of approximately 6 to 8 mum. The results show
      that it is feasible to differentiate and mature hESCs into functional oxygen
      carrying erythrocytes on a large scale.

PMID- 18713949
TI  - Patterning of inflorescences and flowers by the F-Box protein DOUBLE TOP and the
      LEAFY homolog ABERRANT LEAF AND FLOWER of petunia.
AB  - Angiosperms display a wide variety of inflorescence architectures differing in
      the positions where flowers or branches arise. The expression of floral meristem
      identity (FMI) genes determines when and where flowers are formed. In Arabidopsis
      thaliana, this is regulated via transcription of LEAFY (LFY), which encodes a
      transcription factor that promotes FMI. We found that this is regulated in
      petunia (Petunia hybrida) via transcription of a distinct gene, DOUBLE TOP (DOT),
      a homolog of UNUSUAL FLORAL ORGANS (UFO) from Arabidopsis. Mutation of DOT or its
      tomato (Solanum lycopersicum) homolog ANANTHA abolishes FMI. Ubiquitous
      expression of DOT or UFO in petunia causes very early flowering and transforms
      the inflorescence into a solitary flower and leaves into petals. Ectopic
      expression of DOT or UFO together with LFY or its homolog ABERRANT LEAF AND
      FLOWER (ALF) in petunia seedlings activates genes required for identity or
      outgrowth of organ primordia. DOT interacts physically with ALF, suggesting that
      it activates ALF by a posttranslational mechanism. Our findings suggest a wider
      role than previously thought for DOT and UFO in the patterning of flowers and
      indicate that the different roles of LFY and UFO homologs in the spatiotemporal
      control of floral identity in distinct species result from their divergent
      expression patterns.

PMID- 18713950
TI  - The MADS domain protein DIANA acts together with AGAMOUS-LIKE80 to specify the
      central cell in Arabidopsis ovules.
AB  - MADS box genes in plants consist of MIKC-type and type I genes. While MIKC-type
      genes have been studied extensively, the functions of type I genes are still
      poorly understood. Evidence suggests that type I MADS box genes are involved in
      embryo sac and seed development. We investigated two independent T-DNA insertion
      alleles of the Arabidopsis thaliana type I MADS box gene AGAMOUS-LIKE61 (AGL61)
      and showed that in agl61 mutant ovules, the polar nuclei do not fuse and central
      cell morphology is aberrant. Furthermore, the central cell begins to degenerate
      before fertilization takes place. Although pollen tubes are attracted and
      perceived by the mutant ovules, neither endosperm development nor zygote
      formation occurs. AGL61 is expressed in the central cell during the final stages
      of embryo sac development. An AGL61:green fluorescent protein-beta-glucoronidase
      fusion protein localizes exclusively to the polar nuclei and the secondary
      nucleus of the central cell. Yeast two-hybrid analysis showed that AGL61 can form
      a heterodimer with AGL80 and that the nuclear localization of AGL61 is lost in
      the agl80 mutant. Thus, AGL61 and AGL80 appear to function together to
      differentiate the central cell in Arabidopsis. We renamed AGL61 DIANA, after the
      virginal Roman goddess of the hunt.

PMID- 18713951
TI  - Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters
      revisited.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are often regarded as substrates
      for the H+/peptide transporters (PEPT)1 and PEPT2. Even though the conclusions
      drawn from published data are quite inconsistent, in most review articles PEPT1
      is claimed to mediate the intestinal absorption of ACE inhibitors and thus to
      determine their oral availability. We systematically investigated the interaction
      of a series of ACE inhibitors with PEPT1 and PEPT2. First, we studied the effect
      of 14 ACE inhibitors including new drugs on the uptake of the dipeptide
      [14C]glycylsarcosine into human intestinal Caco-2 cells constitutively expressing
      PEPT1 and rat renal SKPT cells expressing PEPT2. In a second approach, the
      interaction of ACE inhibitors with heterologously expressed human PEPT1 and PEPT2
      was determined. In both assay systems, zofenopril and fosinopril were found to
      have very high affinity for binding to peptide transporters. Medium to low
      affinity for transporter interaction was found for benazepril, quinapril,
      trandolapril, spirapril, cilazapril, ramipril, moexipril, quinaprilat, and
      perindopril. For enalapril, lisinopril, and captopril, very weak affinity or lack
      of interaction was found. Transport currents of PEPT1 and PEPT2 expressed in
      Xenopus laevis oocytes were recorded by the two-electrode voltage-clamp
      technique. Statistically significant, but very low currents were only observed
      for lisinopril, enalapril, quinapril, and benazepril at PEPT1 and for spirapril
      at PEPT2. For the other ACE inhibitors, electrogenic transport activity was
      extremely low or not measurable at all. The present results suggest that peptide
      transporters do not control intestinal absorption and renal reabsorption of ACE
      inhibitors.

PMID- 18713952
TI  - The inhibitory effect of 2-halo derivatives of D-glucose on glycolysis and on the
      proliferation of the human malaria parasite Plasmodium falciparum.
AB  - The intraerythrocytic stage of the human malaria parasite Plasmodium falciparum
      relies on glycolysis for ATP generation, and because it has no energy stores, a
      constant supply of glucose is necessary for the parasite to grow and multiply.
      The 2-substituted glucose analogs 2-deoxy-D-glucose (2-DG) and 2-fluoro-2-deoxy-D
      glucose (2-FG) have been previously shown to inhibit the in vitro growth of P.
      falciparum and have been suggested to do so by inhibiting glycosylation in the
      parasite. In this study, we have investigated the antiplasmodial mechanism of
      action of 2-DG and 2-FG and compared it with that of other 2-substituted-glucose
      analogs. The compounds tested inhibited parasite growth to varying degrees, with
      2-FG being the most effective. The antiplasmodial activity of some, but not all,
      of the analogs could be altered by varying the glucose concentration in the
      culture medium, increasing the antiplasmodial activity of the analogs as the
      glucose concentration is reduced. A trend was observed between the antiplasmodial
      activity of these analogs and their ability to inhibit glucose accumulation,
      glucose phosphorylation by hexokinase, and cytosolic pH regulation within the
      intraerythrocytic stage of the parasite. Our data are consistent with inhibition
      of glycolysis being a primary mechanism by which 2-DG and 2-FG inhibit parasite
      growth, and they validate the early steps in glycolysis as viable drug targets.

PMID- 18713953
TI  - Quality of life in low-grade glioma patients receiving temozolomide.
AB  - The purpose of this study was to describe the quality of life (QOL) of low-grade
      glioma (LGG) patients at baseline prior to chemotherapy and through 12 cycles of
      temozolomide (TMZ) chemotherapy. Patients with histologically confirmed LGG with
      only prior surgery were given TMZ for 12 cycles. QOL assessments by the
      Functional Assessment of Cancer Therapy-Brain (FACT-Br) were obtained at baseline
      prior to chemotherapy and at 2-month intervals while receiving TMZ. Patients with
      LGG at baseline prior to chemotherapy had higher reported social well-being
      scores (mean difference = 5.0; p < 0.01) but had lower reported emotional well
      being scores (mean difference = 2.2; p < 0.01) compared to a normal population.
      Compared to patients with left hemisphere tumors, patients with right hemisphere
      tumors reported higher physical well-being scores (p = 0.01): 44% could not
      drive, 26% did not feel independent, and 26% were afraid of having a seizure.
      Difficulty with work was noted in 24%. Mean change scores at each chemotherapy
      cycle compared to baseline for all QOL subscales showed either no significant
      change or were significantly positive (p < 0.01). Patients with LGG on TMZ at
      baseline prior to chemotherapy reported QOL comparable to a normal population
      with the exception of social and emotional well-being, and those with right
      hemisphere tumors reported higher physical well-being scores compared to those
      with left hemisphere tumors. While remaining on therapy, LGG patients were able
      to maintain their QOL in all realms. LGG patients' QOL may be further improved by
      addressing their emotional well-being and their loss of independence in terms of
      driving or working.

PMID- 18713954
TI  - Neural control of the anorexia-cachexia syndrome.
AB  - The anorexia-cachexia syndrome is a debilitating clinical condition
      characterizing the course of chronic diseases, which heavily impacts on patients'
      morbidity and quality of life, ultimately accelerating death. The pathogenesis is
      multifactorial and reflects the complexity and redundancy of the mechanisms
      controlling energy homeostasis under physiological conditions. Accumulating
      evidence indicates that, during disease, disturbances of the hypothalamic
      pathways controlling energy homeostasis occur, leading to profound metabolic
      changes in peripheral tissues. In particular, the hypothalamic melanocortin
      system does not respond appropriately to peripheral inputs, and its activity is
      diverted largely toward the promotion of catabolic stimuli (i.e., reduced energy
      intake, increased energy expenditure, possibly increased muscle proteolysis, and
      adipose tissue loss). Hypothalamic proinflammatory cytokines and serotonin, among
      other factors, are key in triggering hypothalamic resistance. These catabolic
      effects represent the central response to peripheral challenges (i.e., growing
      tumor, renal, cardiac failure, disrupted hepatic metabolism) that are likely
      sensed by the brain through the vagus nerve. Also, disease-induced changes in
      fatty acid oxidation within hypothalamic neurons may contribute to the
      dysfunction of the hypothalamic melanocortin system. Ultimately, sympathetic
      outflow mediates, at least in part, the metabolic changes in peripheral tissues.
      Other factors are likely involved in the pathogenesis of the anorexia-cachexia
      syndrome, and their role is currently being elucidated. However, available
      evidence shows that the constellation of symptoms characterizing this syndrome
      should be considered, at least in part, as different phenotypes of common
      neurochemical/metabolic alterations in the presence of a chronic inflammatory
      state.

PMID- 18713955
TI  - Long-term high-fat feeding induces greater fat storage in mice lacking UCP3.
AB  - Uncoupling protein-3 (UCP3) is a mitochondrial inner-membrane protein highly
      expressed in skeletal muscle. While UCP3's function is still unknown, it has been
      hypothesized to act as a fatty acid (FA) anion exporter, protecting mitochondria
      against lipid peroxidation and/or facilitating FA oxidation. The aim of this
      study was to determine the effects of long-term feeding of a 45% fat diet on
      whole body indicators of muscle metabolism in congenic C57BL/6 mice that were
      either lacking UCP3 (Ucp3(-/-)) or had a transgenically induced approximately
      twofold increase in UCP3 levels (UCP3tg). Mice were fed the high-fat (HF) diet
      for a period of either 4 or 8 mo immediately following weaning. After long-term
      HF feeding, UCP3tg mice weighed an average of 15% less than wild-type mice (P <
      0.05) and were 20% less metabolically efficient than both wild-type and Ucp3(-/-)
      mice (P < 0.01). Additionally, wild-type mice had 21% lower, whereas UCP3tg mice
      had 36% lower, levels of adiposity compared with Ucp3(-/-) mice (P < 0.05 and P <
      0.001, respectively), indicating a protective effect of UCP3 against fat gain. No
      differences in whole body oxygen consumption were detected following long-term HF
      feeding. Glucose and insulin tolerance tests revealed that both the UCP3tg and
      Ucp3(-/-) mice were more glucose tolerant and insulin sensitive compared with
      wild-type mice after short-term HF feeding, but this protection was not
      maintained in the long term. Findings indicate that UCP3 is involved in
      protection from fat gain induced by long-term HF feeding, but not in protection
      from insulin resistance.

PMID- 18713957
TI  - The right stuff: beta-cell channels, cycles, and sensors.

PMID- 18713956
TI  - Sequential muscle biopsies during a 6-h tracer infusion do not affect human mixed
      muscle protein synthesis and muscle phenylalanine kinetics.
AB  - Stable isotope tracer experiments of human muscle amino acid and protein kinetics
      often involve a sequential design, with the same subject studied at baseline and
      during an intervention. However, prolonged fasting and sequential muscle biopsies
      from the same area could theoretically affect muscle protein metabolism. The
      purpose of this study was to determine if sequential muscle biopsies and extended
      fasting significantly affect parameters of muscle protein and amino acid kinetics
      in six human subjects. After a 12-h overnight fast, a primed continuous infusion
      of L-[ring-(2)H(5)]phenylalanine was started. After 120 min, we took the first of
      a series of five hourly muscle biopsies from the same vastus lateralis to measure
      mixed muscle protein fractional synthetic rate. Furthermore, between 150-180, 210
      240, and 330-360 min, we measured leg phenylalanine kinetics using the two-pool
      and the three-pool arteriovenous balance models. Tracer enrichments were at
      steady state, and muscle protein FSR and phenylalanine kinetics did not change
      throughout the experiment (P=not significant). We conclude that a 6-h tracer
      infusion during extended fasting (up to 18 h) with five sequential muscle
      biopsies from the same muscle do not affect basal mixed muscle protein synthesis
      and muscle phenylalanine kinetics in human subjects. Thus, when using a
      sequential study design over this period of time, it is unnecessary to include a
      saline only control group to account for these variables.

PMID- 18713958
TI  - Synaptotagmins bind calcium to release insulin.
AB  - Plasma insulin levels are determined mainly by the rate of exocytosis of the
      insulin-containing large dense core vesicles (LDCVs) of pancreatic islet beta
      cells. This process involves the recruitment of LDCVs to the plasma membrane,
      where they are docked by the assembly of multiprotein SNARE (soluble N
      ethylmaleimide-sensitive factor attachment protein receptor) complexes. However,
      fusion of the two membranes will proceed only in the presence of Ca(2+) ions,
      implicating a Ca(2+) sensor protein. The synaptotagmin gene family, comprising 15
      members, was proposed to act as such Ca(2+) sensor in regulated exocytosis in
      neurons and neuroendocrine and endocrine cells. Herein, we review the
      physiological function of the various synaptotagmins with reference to their
      impact on insulin exocytosis. Cumulating evidence emphasizes the crucial role of
      synaptotagmin VII and IX as mediators of glucose-induced insulin secretion.

PMID- 18713960
TI  - Corticotropin-releasing hormone stimulates SGK-1 kinase expression in cultured
      hippocampal neurons via CRH-R1.
AB  - Corticotropin-releasing hormone (CRH) has been shown to exhibit various functions
      in hippocampus. In the present study, we examined the effect of CRH on the
      expression of serum/glucocorticoid-inducible protein kinase-1 (SGK-1), a novel
      protein kinase, in primary cultured hippocampal neurons. A dose-dependent
      increase in mRNA and protein levels of SGK-1 as well as frequency of SGK-1
      positive neurons occurred upon exposure to CRH (1 pmol/l to 10 nmol/l). These
      effects can be reversed by the specific CRH-R1 antagonist antalarmin but not by
      the CRH-R2 antagonist astressin 2B. Blocking adenylate cyclase (AC) activity with
      SQ22536 and PKA with H89 completely prevented CRH-induced mRNA and protein
      expression of SGK-1. Blockage of PLC or PKC did not block CRH-induced SGK-1
      expression. Our results suggest that CRH act on CRH-R1 to stimulate SGK-1 mRNA
      and protein expression in cultured hippocampal neurons via a mechanism that is
      involved in AC/PKA signaling pathways.

PMID- 18713961
TI  - Abnormalities of IGF-I signaling in the pathogenesis of diseases of the bone,
      brain, and fetoplacental unit in humans.
AB  - IGF-I action is essential for the regulation of tissue formation and remodeling,
      bone growth, prenatal growth, brain development, and muscle metabolism. Cellular
      effects of IGF-I are mediated through the IGF-I receptor, a transmembrane
      tyrosine kinase that phosphorylates intracellular substrates, resulting in the
      activation of multiple intracellular signaling cascades. Dysregulation of IGF-I
      actions due to impairment in the postreceptor signaling machinery may contribute
      to multiple diseases in humans. This article will review current information on
      IGF-I signaling and illustrate recent results demonstrating how impaired IGF-I
      signaling and action may contribute to the pathogenesis of human diseases,
      including osteoporosis, neurodegenerative disorders, and reduced fetal growth in
      utero.

PMID- 18713959
TI  - Skeletal and cardiac myopathy in HIV-1 transgenic rats.
AB  - The mechanism by which human immunodeficiency virus (HIV)-1 infection in humans
      leads to the erosion of lean body mass is poorly defined. Therefore, the purpose
      of the present study was to determine whether transgenic (Tg) rats that
      constitutively overexpress HIV-1 viral proteins exhibit muscle wasting and to
      elucidate putative mechanisms. Over 7 mo, Tg rats gained less body weight than
      pair-fed controls exclusively as a result of a proportional reduction in lean,
      not fat, mass. Fast- and slow-twitch muscle atrophy in Tg rats did not result
      from a reduction in the in vivo-determined rate of protein synthesis. In
      contrast, urinary excretion of 3-methylhistidine, as well as the content of
      atrogin-1 and the 14-kDa actin fragment, was elevated in gastrocnemius of Tg
      rats, suggesting increased muscle proteolysis. Similarly, Tg rats had reduced
      cardiac mass, which was independent of a change in protein synthesis. This
      decreased cardiac mass was associated with a reduction in stroke volume, but
      cardiac output was maintained by a compensatory increase in heart rate. The HIV
      induced muscle atrophy was associated with increased whole body energy
      expenditure, which was not due to an elevated body temperature or secondary
      bacterial infection. Furthermore, the atrophic response could not be attributed
      to the development of insulin resistance, decreased levels of circulating amino
      acids, or increased tissue cytokines. However, skeletal muscle and, to a lesser
      extent, circulating insulin-like growth factor I was reduced in Tg rats. Although
      hepatic injury was implicated by increased plasma levels of aspartate and alanine
      aminotransferases, hepatic protein synthesis was not different between control
      and Tg rats. Hence, HIV-1 Tg rats develop atrophy of cardiac and skeletal muscle,
      the latter of which results primarily from an increased protein degradation and
      may be related to the marked reduction in muscle insulin-like growth factor I.

PMID- 18713962
TI  - Adaptation to intermittent stress promotes maintenance of beta-cell compensation:
      comparison with food restriction.
AB  - Intermittent restraint stress delays hyperglycemia in ZDF rats better than pair
      feeding. We hypothesized that intermittent stress would preserve beta-cell mass
      through distinct mechanisms from food restriction. We studied temporal effects of
      intermittent stress on beta-cell compensation during pre-, early, and late
      diabetes. Six-week-old obese male ZDF rats were restraint-stressed 1 h/day, 5
      days/wk for 0, 3, 6, or 13 wk and compared with age-matched obese ZDF rats that
      had been food restricted for 13 wk, and 19-wk-old lean ZDF rats. Thirteen weeks
      of stress and food restriction lowered cumulative food intake 10-15%. Obese
      islets were fibrotic and disorganized and not improved by stress or food
      restriction. Obese pancreata had islet hyperplasia and showed evidence of
      neogenesis, but by 19 wk old beta-cell mass was not increased, and islets had
      fewer beta-cells that were hypertrophic. Both stress and food restriction
      partially preserved beta-cell mass at 19 wk old via islet hypertrophy, whereas
      stress additionally lowered alpha-cell mass. Concomitant with maintenance of
      insulin responses to glucose, stress delayed the sixfold decline in beta-cell
      proliferation and reduced beta-cell hypertrophy, translating into 30% more beta
      cells per islet after 13 wk. In contrast, food restriction did not improve
      insulin responses or beta-cell hyperplasia, exacerbated beta-cell hypertrophy,
      and resulted in fewer beta-cells and greater alpha-cell mass than with stress.
      Thus, preservation of beta-cell mass with adaptation to intermittent stress is
      related to beta-cell hyperplasia, maintenance of insulin responses to glucose,
      and reductions in alpha-cell mass that do not occur with food restriction.

PMID- 18713963
TI  - IL-4 production by T cells: you need a little to get a lot.

PMID- 18713964
TI  - Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and
      IL-4 are required for in vitro generation of IL-4-producing cells.

PMID- 18713965
TI  - Comparative functional evolution of human and mouse CR1 and CR2.

PMID- 18713966
TI  - B cell depletion with anti-CD79 mAbs ameliorates autoimmune disease in MRL/lpr
      mice.
AB  - MRL/lpr mice develop a spontaneous systemic lupus erythematosus-like autoimmune
      syndrome due to a dysfunctional Fas receptor, with contributions from other less
      well-defined genetic loci. The removal of B cells by genetic manipulation not
      only prevents autoantibody formation, but it also results in substantially
      reduced T cell activation and kidney inflammation. To determine whether B cell
      depletion by administration of Abs is effective in lupus mice with an intact
      immune system and established disease, we screened several B cell-specific mAbs
      and found that a combination of anti-CD79alpha and anti-CD79beta Abs was most
      effective at depleting B cells in vivo. Anti-CD79 therapy started at 4-5 mo of
      age in MRL/lpr mice significantly decreased B cells (B220(+)CD19(+)) in
      peripheral blood, bone marrow, and spleens. Treated mice also had a significant
      increase in the number of both double-negative T cells and naive CD4(+) T cells,
      and a decreased relative abundance of CD4(+) memory cells. Serum anti-chromatin
      IgG levels were significantly decreased compared with controls, whereas serum
      anti-dsDNA IgG, total IgG, or total IgM were unaffected. Overall, survival was
      improved with lower mean skin scores and significantly fewer focal inflammatory
      infiltrates in submandibular salivary glands and kidneys. Anti-CD79 mAbs show
      promise as a potential treatment for systemic lupus erythematosus and as a model
      for B cell depletion in vivo.

PMID- 18713968
TI  - FOXO1 regulates L-Selectin and a network of human T cell homing molecules
      downstream of phosphatidylinositol 3-kinase.
AB  - In T cells, the PI3K pathway promotes proliferation and survival induced by Ag or
      growth factors, in part by inactivating the FOXO transcription factor 1. We now
      report that FOXO1 controls the expression of L-selectin, an essential homing
      molecule, in human T lymphocytes. This control is already operational in unprimed
      T cells and involves a transcriptional regulation process that requires the FOXO1
      DNA-binding domain. Using transcriptional profiling, we demonstrate that FOXO1
      also increases transcripts of EDG1 and EDG6, two sphingosine-1-phosphate
      receptors that regulate lymphocyte trafficking. Additionally, FOXO1 binds the
      promoter of the cell quiescence and homing regulator Kruppel-like factor 2 and
      regulates its expression. Together, these results reveal a new function of FOXO1
      in the immune system and suggest that PI3K controls a coordinated network of
      transcription factors regulating both cell quiescence and homing of human T
      lymphocytes.

PMID- 18713967
TI  - B and T lymphocyte attenuator regulates T cell survival in the lung.
AB  - The initiation, intensity, and duration of T cell-directed inflammatory responses
      are dependent upon the coordination of both activating and inhibitory signals
      mediated by specific receptors on the T lymphocyte. The recently described
      receptor, B and T lymphocyte attenuator (BTLA), has been demonstrated to have an
      important role in limiting the duration of inflammation in a murine model of
      allergic asthma. In this study, we have examined the role of BTLA on the
      proliferation, recruitment, and survival of T cells in response to inhaled
      allergen. We find that there is decreased cell death in T cells from BTLA
      deficient mice, whereas proliferation and recruitment to the lungs are unchanged.
      Thus, the regulation of cell death through BTLA signaling is a key determinant of
      the inflammatory response in the lung.

PMID- 18713969
TI  - Targeting CpG oligonucleotides to the lymph node by nanoparticles elicits
      efficient antitumoral immunity.
AB  - Viral nucleic acids are recognized by specific pattern-recognition receptors of
      the Toll-like and RIG-I-like receptor families. Synthetic DNA and RNA
      oligonucleotides can activate the immune system through these receptors and
      potentiate Ab and CD8 cytotoxic responses to Ags. Systemic application of
      immunostimulatory oligonucleotides however also results in a generalized, non-Ag
      specific stimulation of the immune system. In this study, we have dissociated the
      induction of an Ag-specific response from the systemic immune activation
      generally associated with immunostimulatory oligonucleotides. Delivery of CpG
      oligodeoxynucleotides that bind TLR9 by cationized gelatin-based nanoparticles
      potentiates the in vivo generation of an Ag-specific cytotoxic T cell and Ab
      response. Furthermore, immunization with CpG-loaded nanoparticles induces a
      protective antitumoral response in a murine model of melanoma. The systemic
      release of proinflammatory cytokines and widespread immunostimulation associated
      with free CpG is however completely abolished. In addition, we show that gelatin
      nanoparticle formulation prevents the destruction of lymphoid follicles mediated
      by CpG. Nanoparticle-delivered CpG, in contrast to free CpG, are selectively
      targeted to APCs in the lymph nodes where they mediate local immune stimulation.
      We describe a novel strategy to target immunostimulatory oligonucleotides to the
      initiation site of the immune response while at the same time protecting from an
      indiscriminate and generalized activation of the immune system.

PMID- 18713970
TI  - Induction of CD83+CD14+ nondendritic antigen-presenting cells by exposure of
      monocytes to IFN-alpha.
AB  - IFN-alpha is a well-known agent for treatment of viral and malignant diseases. It
      has several modes of actions, including direct influence on the immune system. We
      investigated IFN-alpha effects on PBMC in terms of dendritic cell (DC)
      differentiation, as PBMC are exposed to high IFN-alpha levels during treatment of
      infections and cancers. We show that in vitro IFN-alpha exposure induced rapid
      and strong up-regulation of the DC-maturation markers CD80, CD86, and CD83 in
      bulk PBMC. Consistently, IFN-alpha induced up-regulation of these molecules on
      purified monocytes within 24 h. Up-regulation of CD80 and CD83 expression was IFN
      alpha concentration-dependent. In contrast to GM-CSF + IL-4-generated DCs, most
      of the IFN-alpha-challenged CD83(+) cells coexpressed the monocyte marker CD14.
      Despite a typical mature DC immunophenotype, IFN-alpha-treated monocytes
      conserved phagocytic activity and never acquired a dendritic morphology. In mixed
      lymphocyte reactions IFN-alpha-treated monocytes were less potent than GM-CSF +
      IL-4-generated DCs but significantly more potent than untreated monocytes to
      induce T cell proliferation in bulk PBMC. However, only GM-CSF + IL-4-generated
      DCs were able to induce a significant proliferation of naive CD4(+) T cells.
      Notably, autologous memory CD4(+) T cells proliferated when exposed to tetanus
      toxoid-pulsed IFN-alpha-treated monocytes. At variance with untreated or GM-CSF +
      IL-4-exposed monocytes, those challenged with IFN-alpha showed long-lasting STAT
      1 phosphorylation. Remarkably, CD83(+)CD14(+) cells were present in varicella
      skin lesions in close contact with IFN-alpha-producing cells. The present
      findings suggest that IFN-alpha alone promptly generates nondendritic APCs able
      to stimulate memory immune responses. This may represent an additional mode of
      action of IFN-alpha in vivo.

PMID- 18713971
TI  - Critical and differential roles of NKp46- and NKp30-activating receptors
      expressed by uterine NK cells in early pregnancy.
AB  - In early human pregnancy, uterine decidual NK cells (dNK) are abundant and
      considered as cytokine producers but poorly cytotoxic despite their cytolytic
      granule content, suggesting a negative control of this latter effector function.
      To investigate the basis of this control, we examined the relative contribution
      to the cytotoxic function of different activating receptors expressed by dNK.
      Using a multicolor flow cytometry analysis, we found that freshly isolated dNK
      exhibit a unique repertoire of activating and inhibitory receptors, identical
      among all the donors tested. We then demonstrated that in fresh dNK, mAb-specific
      engagement of NKp46-, and to a lesser extent NKG2C-, but not NKp30-activating
      receptors induced intracellular calcium mobilization, perforin polarization,
      granule exocytosis and efficient target cell lysis. NKp46-mediated cytotoxicity
      is coactivated by CD2 but dramatically blocked by NKG2A coengagement, indicating
      that the dNK cytotoxic potential could be tightly controlled in vivo. We finally
      found that in dNK, mAb-specific engagement of NKp30, but not NKp46, triggered the
      production of IFN-gamma, TNF-alpha, MIP-1alpha, MIP-1beta, and GM-CSF
      proinflammatory molecules. These data demonstrate a differential, controlled role
      of NKp46- and NKp30-activating receptors expressed by dNK that could be critical
      for the outcome of pregnancy and the killing of uterine cells infected by
      pathogens.

PMID- 18713972
TI  - Apoptotic cell-mediated immunoregulation of dendritic cells does not require iC3b
      opsonization.
AB  - A number of recent studies show that activation of CR3 on dendritic cells (DCs)
      suppresses TLR-induced TNF-alpha and IL-12 production and inhibits effective Ag
      presentation. Although the proposed physiologic role for these phenomena is
      immune suppression due to recognition of iC3b opsonized apoptotic cells by CR3,
      all of the aforementioned investigations used artificial means of activating CR3.
      We investigated whether iC3b opsonized apoptotic cells could induce the same
      changes reported with artificial ligands such as mAbs or iC3b-opsonized RBC. We
      explored the kinetics of iC3b opsonization in two models of murine cell
      apoptosis, gamma-irradiated thymocytes and cytokine deprivation of the IL-3
      dependent cell line BaF3. Using a relatively homogenous population of early
      apoptotic cells (IL-3 deprived BaF3 cells), we show that iC3b opsonized apoptotic
      cells engage CR3, but this interaction is dispensable in mediating the anti
      inflammatory effects of apoptotic cells. TLR-induced TNF-alpha and IL-12
      production by bone marrow-derived DCs occurs heterogeneously, with apoptotic
      cells inhibiting only certain populations depending on the TLR agonist. In
      contrast, although apoptotic cells induced homogeneous IL-10 production by DCs,
      IL-10 was not necessary for the inhibition of TNF-alpha and IL-12. Furthermore,
      because the ability of iC3b opsonization to enhance phagocytosis of apoptotic
      cells has been controversial, we report that iC3b opsonization does not
      significantly affect apoptotic cell ingestion by DCs. We conclude that the
      apoptotic cell receptor system on DCs is sufficiently redundant such that the
      absence of CR3 engagement does not significantly affect the normal anti
      inflammatory processing of apoptotic cells.

PMID- 18713973
TI  - Role of endogenous brain-derived neurotrophic factor and sortilin in B cell
      survival.
AB  - Brain-derived neurotrophic factor (BDNF), a major neuronal growth factor, is also
      known to exert an antiapoptotic effect in myeloma cells. Whereas BDNF secretion
      was described in B lymphocytes, the ability of B cells to produce sortilin, its
      transport protein, was not previously reported. We studied BDNF production and
      the expression of its receptors, tyrosine protein kinase receptor B and p75
      neurotrophin receptor in the human pre-B, mature, and plasmacytic malignant B
      cell lines under normal and stress culture conditions (serum deprivation, Fas
      activation, or their combination). BDNF secretion was enhanced by serum
      deprivation and exerted an antiapoptotic effect, as demonstrated by
      neutralization experiments with antagonistic Ab. The precursor form, pro-BDNF,
      also secreted by B cells, decreases under stress conditions in contrast to BDNF
      production. Stress conditions induced the membranous expression of p75
      neurotrophin receptor and tyrosine protein kinase receptor B, maximal in mature B
      cells, contrasting with the sequestration of both receptors in normal culture. By
      blocking Ab and small interfering RNA, we evidenced that BDNF production and its
      survival function are depending on sortilin, a protein regulating neurotrophin
      transport in neurons, which was not previously described in B cells. Therefore,
      in mature B cell lines, an autocrine BDNF production is up-regulated by stress
      culture conditions and exerts a modulation of apoptosis through the sortilin
      pathway. This could be of importance to elucidate certain drug resistances of
      malignant B cells. In addition, primary B lymphocytes contained sortilin and
      produced BDNF after mitogenic activation, which suggests that sortilin and BDNF
      might be implicated in the survival and activation of normal B cells also.

PMID- 18713975
TI  - TRIF and IRF-3 binding to the TNF promoter results in macrophage TNF
      dysregulation and steatosis induced by chronic ethanol.
AB  - Chronic ethanol (EtOH) abuse results in the development of steatosis, alcoholic
      hepatitis, and cirrhosis. Augmented TNF-alpha production by macrophages and
      Kupffer cells and signaling via the p55 TNF receptor have been shown to be
      critical for these effects of chronic EtOH; however, the molecular mechanisms
      leading to augmented TNF-alpha production remain unclear. Using cell culture
      models and in vivo studies we demonstrate that chronic EtOH results in increased
      TNF-alpha transcription, which is independent of NF-kappaB. Using reporter assays
      and chromatin immunoprecipitation we found that this increased transcription is
      due to increased IRF-3 binding to and transactivation of the TNF promoter. As IRF
      3 is downstream from the TLR4 adaptor TIR-domain-containing adapter-inducing IFN
      beta (Trif), we demonstrate that macrophages from Trif-/- mice are resistant to
      this dysregulation of TNF-alpha transcription by EtOH in vitro as well as EtOH
      induced steatosis and TNF dysregulation in vivo. These data demonstrate that the
      Trif/IRF-3 pathway is a target to ameliorate liver dysfunction associated with
      chronic EtOH.

PMID- 18713976
TI  - Cannabinoids affect dendritic cell (DC) potassium channel function and modulate
      DC T cell stimulatory capacity.
AB  - Cannabinoids affect diverse biological processes, including functions of the
      immune system. With respect to the immune system, anti-inflammatory and
      immunosuppressive effects of cannabinoids have been reported. Cannabinoids
      stimulate G protein-coupled cannabinoid receptors CB1 and CB2. These receptors
      are found primarily on neurons. However, they are also found on dendritic cells
      (DC), which are recognized for their critical role in initiating and maintaining
      immune responses. Therefore, DC are potential targets for cannabinoids. We report
      in this study that cannabinoids reduced the DC surface expression of MHC class II
      molecules as well as their capacity to stimulate T cells. In the nervous system,
      CB1 receptor signaling modulates K(+) and Ca(2+) channels. Interestingly,
      cannabinoid-treated DC also showed altered voltage-gated potassium (K(V)) channel
      function. We speculate that attenuation of K(V) channel function via CB1 receptor
      signaling in DC may represent one mechanism by which cannabinoids alter DC
      function.

PMID- 18713974
TI  - Immunodominance of CD4 T cells to foreign antigens is peptide intrinsic and
      independent of molecular context: implications for vaccine design.
AB  - Immunodominance refers to the restricted peptide specificity of T cells that are
      detectable after an adaptive immune response. For CD4 T cells, many of the
      mechanisms used to explain this selectivity suggest that events related to Ag
      processing play a major role in determining a peptide's ability to recruit CD4 T
      cells. Implicit in these models is the prediction that the molecular context in
      which an antigenic peptide is contained will impact significantly on its
      immunodominance. In this study, we present evidence that the selectivity of CD4 T
      cell responses to peptides contained within protein Ags is not detectably
      influenced by the location of the peptide in a given protein or the primary
      sequence of the protein that bears the test peptide. We have used molecular
      approaches to change the location of peptides within complex protein Ags and to
      change the flanking sequences that border the peptide epitope to now include a
      protease site, and find that immunodominance or crypticity of a peptide observed
      in its native protein context is preserved. Collectively, these results suggest
      immunodominance of peptides contained in complex Ags is due to an intrinsic
      factor of the peptide, based upon the affinity of that peptide for MHC class II
      molecules. These findings are discussed with regard to implications for vaccine
      design.

PMID- 18713977
TI  - Antigen persistence is required for dendritic cell licensing and CD8+ T cell
      cross-priming.
AB  - It has been demonstrated that CD4(+) T cells require Ag persistence to achieve
      effective priming, whereas CD8(+) T cells are on "autopilot" after only a brief
      exposure. This finding presents a disturbing conundrum as it does not account for
      situations in which CD8(+) T cells require CD4(+) T cell help. We used a
      physiologic in vivo model to study the requirement of Ag persistence for the
      cross-priming of minor histocompatibility Ag-specific CD8(+) T cells. We report
      inefficient cross-priming in situations in which male cells are rapidly cleared.
      Strikingly, the failure to achieve robust CD8(+) T cell activation is not due to
      a problem with cross-presentation. In fact, by providing "extra help" in the form
      of dendritic cells (DCs) loaded with MHC class II peptide, it was possible to
      achieve robust activation of CD8(+) T cells. Our data suggest that the
      "licensing" of cross-presenting DCs does not occur during their initial encounter
      with CD4(+) T cells, thus accounting for the requirement for Ag persistence and
      suggesting that DCs make multiple interactions with CD8(+) T cells during the
      priming phase. These findings imply that long-lived Ag is critical for efficient
      vaccination protocols in which the CD8(+) T cell response is helper-dependent.

PMID- 18713978
TI  - A critical role for the proapoptotic protein bid in ultraviolet-induced immune
      suppression and cutaneous apoptosis.
AB  - Apoptosis plays an important role in eliminating UV-damaged keratinocytes, but
      its role in UV-induced immune suppression is not clear. Langerhans cells (LCs)
      may function as inducers of immune suppression. We have shown that LCs derived
      from mice deficient in the proapoptotic Bid (BH3-interacting death domain
      protein) gene (Bid KO) resist apoptosis and induce amplified immune responses. In
      this report, we examined responses in Bid KO mice to UVB exposure. Acute UV
      exposure led Bid KO mice to develop fewer apoptotic cells and retain a greater
      fraction of LCs in the epidermal layer of skin in comparison to wild-type mice.
      Bid KO mice were also markedly resistant to local and systemic UV tolerance
      induction to hapten sensitization and contact hypersensitivity responses.
      Elicitation responses and inflammation at skin sensitization sites in UV-treated
      Bid KO mice were equal to or greater than nonsuppressed control responses. In Bid
      KO mice, LCs accumulated in lymph nodes to greater numbers, demonstrated longer
      lifespans, and contained fewer DNA-damaged cells. These studies provide evidence
      that Bid activation is a critical upstream mediator in UV-induced keratinocyte
      and LC apoptosis and that its absence abrogates UV-induced immune tolerance.

PMID- 18713979
TI  - Tumor-educated tolerogenic dendritic cells induce CD3epsilon down-regulation and
      apoptosis of T cells through oxygen-dependent pathways.
AB  - Defects in the CD3/TCR complex and impairment of T cell function are necessary
      for tumor evasion, but the underlying mechanisms are incompletely understood. We
      found that culture supernatants from several types of solid tumor cell lines
      drove human monocytes to become tolerogenic semimature dendritic cells (TDCs).
      Upon encountering T cells, the TDCs triggered rapid down-regulation of CD3epsilon
      and TCR-alpha/beta and subsequent apoptosis in autologous T cells. Consistent
      with these results, accumulation of immunosuppressive DCs coincided with
      CD3epsilon down-regulation and T cell deletion in cancer nests of human tumors.
      The impaired T cell function was mediated by factor(s) released by live TDCs
      after direct interaction with lymphocytes. Also, the TDC-induced effect on T
      cells was markedly reduced by blocking of NADPH oxidase but not by inhibition of
      arginase, inducible NO synthase (iNOS), IDO, or IFN-gamma. Moreover, we found
      that hyaluronan fragments constituted a common factor produced by a variety of
      human tumor cell lines to induce formation of TDCs. These observations indicate
      that tumor microenvironments, including hyaluronan fragments derived from cancer
      cells, educate DCs to adopt a semimature phenotype, which in turn aids tumor
      immune escape by causing defects in the CD3/TCR complex and deletion of T cells.

PMID- 18713980
TI  - Radiation-induced CXCL16 release by breast cancer cells attracts effector T
      cells.
AB  - Recruitment of effector T cells to inflamed peripheral tissues is regulated by
      chemokines and their receptors, but the factors regulating recruitment to tumors
      remain largely undefined. Ionizing radiation (IR) therapy is a common treatment
      modality for breast and other cancers. Used as a cytocidal agent for
      proliferating cancer cells, IR in combination with immunotherapy has been shown
      to promote immune-mediated tumor destruction in preclinical studies. In this
      study we demonstrate that IR markedly enhanced the secretion by mouse and human
      breast cancer cells of CXCL16, a chemokine that binds to CXCR6 on Th1 and
      activated CD8 effector T cells, and plays an important role in their recruitment
      to sites of inflammation. Using a poorly immunogenic mouse model of breast
      cancer, we found that irradiation increased the migration of CD8(+)CXCR6(+)
      activated T cells to tumors in vitro and in vivo. CXCR6-deficient mice showed
      reduced infiltration of tumors by activated CD8 T cells and impaired tumor
      regression following treatment with local IR to the tumor and Abs blocking the
      negative regulator of T cell activation, CTLA-4. These results provide the first
      evidence that IR can induce the secretion by cancer cells of proinflammatory
      chemotactic factors that recruit antitumor effector T cells. The ability of IR to
      convert tumors into "inflamed" peripheral tissues could be exploited to overcome
      obstacles at the effector phase of the antitumor immune response and improve the
      therapeutic efficacy of immunotherapy.

PMID- 18713981
TI  - OK432-activated human dendritic cells kill tumor cells via CD40/CD40 ligand
      interactions.
AB  - In vivo, dendritic cells (DC) are programmed to orchestrate innate and adaptive
      immunity in response to pathogen-derived "danger" signals. Under particular
      circumstances, DC can also be directly cytotoxic against tumor cells, potentially
      allowing them to release tumor associated Ags from dying cells and then prime
      antitumor immunity against them. In this study, we describe the innate
      characteristics of DC (OK-DC) generated in vitro after exposure of immature human
      myeloid-derived DC to OK432, a penicillin-inactivated and lyophilized preparation
      of Streptococcus pyrogenes. OK-DC produced proinflammatory cytokines, stimulated
      autologous T cell proliferation and IFN-gamma secretion, expressed CCR7, and
      migrated in response to MIP-3beta. Moreover, OK-DC displayed strong, specific
      cytotoxicity toward tumor cell targets. This cytotoxicity was associated with
      novel, OK432-induced up-regulation of CD40L on the cell surface of OK-DC, and was
      absolutely dependent on expression of CD40 on the tumor targets. These data
      demonstrate that maturation of human DC with OK432, an adjuvant suitable for
      clinical use, induces direct tumor cell killing by DC, and describes a novel
      CD40/CD40L-mediated mechanism for specific DC antitumor cytotoxicity.

PMID- 18713982
TI  - MUC1 enhances tumor progression and contributes toward immunosuppression in a
      mouse model of spontaneous pancreatic adenocarcinoma.
AB  - MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly
      glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role
      of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an
      appropriate model. We report the characterization of a novel mouse model that
      expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise
      in an appropriate MUC1-tolerant background within an immune-competent host.
      Significant enhancement in the development of pancreatic intraepithelial
      preneoplastic lesions and progression to adenocarcinoma is observed in PDA.MUC1
      mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express
      higher levels of cyclooxygenase-2 and IDO compared with PDA mice lacking MUC1,
      especially during early stages of tumor development. The increased
      proinflammatory milieu correlates with an increased percentage of regulatory T
      cells and myeloid suppressor cells in the pancreatic tumor and tumor draining
      lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated
      mechanisms enhance the onset and progression of the disease, which in turn
      regulate the immune responses. Thus, the mouse model is ideally suited for
      testing novel chemopreventive and therapeutic strategies against pancreatic
      cancer.

PMID- 18713983
TI  - Sodium-dependent glucose transporter-1 as a novel immunological player in the
      intestinal mucosa.
AB  - In this study, we demonstrate the protective effect of the activation of sodium
      dependent glucose transporter-1 (SGLT-1) on damages induced by TLR ligands, in
      intestinal epithelial cells and in a murine model of septic shock. In intestinal
      epithelial cell lines, glucose inhibited the IL-8/keratinocyte-derived chemokine
      production and the activation of the TLR-related transcription factor NF-kappaB
      stimulated by LPS or CpG-oligodeoxynucleotide. Oral ingestion of glucose was
      found to protect 100% of mice from lethal endotoxic shock induced by i.p. LPS
      administration; protection was only observed when glucose was administered
      orally, not by i.p. route, suggesting the important role of intestinal epithelial
      cells in this protection. In addition, we observed that the in vivo protection
      depends on an increase of anti-inflammatory cytokine IL-10. The cornerstone of
      the observed immunomodulatory and life-saving effects resides in activation of
      SGLT-1; in fact, the glucose analog 3-O-methyl-d-gluco-pyranose, which induces
      the transporter activity, but is not metabolized, exerted the same inhibitory
      effects as glucose both in vitro and in vivo. Thus, we propose that activated
      SGLT-1, apart from its classical metabolic function, may be a promising target
      for inhibition of bacteria-induced inflammatory processes and life-saving
      treatments, assuming a novel role as an immunological player.

PMID- 18713985
TI  - The C-type lectin macrophage galactose-type lectin impedes migration of immature
      APCs.
AB  - Dendritic cells (DCs) are the most potent APCs of the immune system that seed the
      peripheral tissues and lymphoid organs. In an immature state, DCs sample their
      surroundings for incoming pathogens. Upon Ag encounter, DCs mature and migrate to
      the lymph node to induce adaptive immune responses. The C-type macrophage
      galactose-type lectin (MGL), expressed in immature DCs, mediates binding to
      glycoproteins carrying GalNAc moieties. In the present study, we demonstrate that
      MGL ligands are present on the sinusoidal and lymphatic endothelium of lymph node
      and thymus, respectively. MGL binding strongly correlated with the expression of
      the preferred MGL ligand, alpha-GalNAc-containing glycan structures, as
      visualized by staining with the alpha-GalNAc-specific snail lectin Helix pomatia
      agglutinin. MGL(+) cells were localized in close proximity of the endothelial
      structures that express the MGL ligand. Strikingly, instead of inducing
      migration, MGL mediated retention of human immature DCs, as blockade of MGL
      interactions enhanced DC trafficking and migration. Thus, MGL(+) DCs are hampered
      in their migratory responses and only upon maturation, when MGL expression is
      abolished; these DCs will be released from their MGL-mediated restraints.

PMID- 18713984
TI  - Reprogrammed FoxP3+ T regulatory cells become IL-17+ antigen-specific autoimmune
      effectors in vitro and in vivo.
AB  - Lymphocyte differentiation from naive CD4(+) T cells into mature Th1, Th2, Th17,
      or T regulatory cell (Treg) phenotypes has been considered end stage in
      character. In this study, we demonstrate that dendritic cells (DCs) activated
      with a novel immune modulator B7-DC XAb (DC(XAb)) can reprogram Tregs into T
      effector cells. Down-regulation of FoxP3 expression after either in vitro or in
      vivo Treg-DC(XAb) interaction is Ag-specific, IL-6-dependent, and results in the
      functional reprogramming of the mature T cell phenotype. The reprogrammed Tregs
      cease to express IL-10 and TGFbeta, fail to suppress T cell responses, and gain
      the ability to produce IFN-gamma, IL-17, and TNF-alpha. The ability of IL-6(+)
      DC(XAb) and the inability of IL-6(-/-) DC(XAb) vaccines to protect animals from
      lethal melanoma suggest that exogenously modulated DC can reprogram host Tregs.
      In support of this hypothesis and as a test for Ag specificity, transfer of
      DC(XAb) into RIP-OVA mice causes a break in immune tolerance, inducing diabetes.
      Conversely, adoptive transfer of reprogrammed Tregs but not similarly treated
      CD25(-) T cells into naive RIP-OVA mice is also sufficient to cause autoimmune
      diabetes. Yet, treatment of normal mice with B7-DC XAb fails to elicit
      generalized autoimmunity. The finding that mature Tregs can be reprogrammed into
      competent effector cells provides new insights into the plasticity of T cell
      lineage, underscores the importance of DC-T cell interaction in balancing
      immunity with tolerance, points to Tregs as a reservoir of autoimmune effectors,
      and defines a new approach for breaking tolerance to self Ags as a strategy for
      cancer immunotherapy.

PMID- 18713986
TI  - Mononuclear phagocyte-derived IL-10 suppresses the innate IL-12/IFN-gamma axis in
      lung-challenged aged mice.
AB  - Previously, we reported that IL-10-producing mononuclear phagocytes increase in
      lungs of aged mice, causing impaired innate cytokine expression. Since dendritic
      cells (DCs) contribute to innate NK cell and adaptive T cell immunity, we tested
      the hypothesis that age-related IL-10 might influence DC function with effects on
      NK and T cell activation. The results showed that DC recruitment to sites of lung
      inflammation was normal in aged mice (>20 mo). However, IFN-gamma-producing NK
      cells in LPS-challenged lungs were decreased in aged as compared with young mice,
      which was associated with increased IL-10(+)CD11b(+)Gr-1(low)CD11c(-) cells
      consistent with mononuclear phagocytes. In vivo or in vitro blockade of IL-10
      signaling restored IFN-gamma-producing NK cells. This restoration was reversed by
      IL-12 neutralization, indicating that IL-10 suppressed sources of IL-12 in aged
      mice. To probe DC function in adaptive immunity, we transferred young naive OVA
      specific TCR transgenic T cells to old mice. Following challenge with OVA plus
      LPS, Ag presentation in the context of MHC-I and MHC-II occurred with similar
      kinetics and intensity in draining lymph nodes of young and old recipients as
      measured by proliferation. Despite this, aged hosts displayed impaired induction
      of IFN-gamma(+)CD4(+), but not IFN-gamma(+)CD8(+), effector T cells. Blockade of
      IL-10 signaling reversed age-associated defects. These studies indicate that the
      innate IL-12/IFN-gamma axis is not intrinsically defective in lungs of aged mice,
      but is rather suppressed by enhanced production of mononuclear phagocyte-derived
      IL-10. Our data identify a novel mechanism of age-associated immune deficiency.

PMID- 18713987
TI  - Expression and functional significance of SOCS-1 and SOCS-3 in astrocytes.
AB  - Astrocytes play a number of important physiological roles in CNS homeostasis.
      Inflammation stimulates astrocytes to secrete cytokines and chemokines that guide
      macrophages/microglia and T cells to sites of injury/inflammation. Herein, we
      describe how these processes are controlled by the suppressor of cytokine
      signaling (SOCS) proteins, a family of proteins that negatively regulate adaptive
      and innate immune responses. In this study, we describe that the immunomodulatory
      cytokine IFN-beta induces SOCS-1 and SOCS-3 expression in primary astrocytes at
      the transcriptional level. SOCS-1 and SOCS-3 transcriptional activity is induced
      by IFN-beta through IFN-gamma activation site (GAS) elements within their
      promoters. Studies in STAT-1alpha-deficient astrocytes indicate that STAT-1alpha
      is required for IFN-beta-induced SOCS-1 expression, while STAT-3 small
      interfering RNA studies demonstrate that IFN-beta-induced SOCS-3 expression
      relies on STAT-3 activation. Specific small interfering RNA inhibition of IFN
      beta-inducible SOCS-1 and SOCS-3 in astrocytes enhances their proinflammatory
      responses to IFN-beta stimulation, such as heightened expression of the
      chemokines CCL2 (MCP-1), CCL3 (MIP-1alpha), CCL4 (MIP-1beta), CCL5 (RANTES), and
      CXCL10 (IP-10), and promoting chemotaxis of macrophages and CD4(+) T cells. These
      results indicate that IFN-beta induces SOCS-1 and SOCS-3 in primary astrocytes to
      attenuate its own chemokine-related inflammation in the CNS.

PMID- 18713988
TI  - KLRE/I1 and KLRE/I2: a novel pair of heterodimeric receptors that inversely
      regulate NK cell cytotoxicity.
AB  - NK cells identify infected, neoplastic, or MHC-disparate target cells via several
      different receptors. The NK cell receptor KLRE1 lacks known signaling motifs but
      has nevertheless been shown to regulate NK cell-mediated cytotoxicity. Here we
      demonstrate that KLRE1 forms functional heterodimers with either KLRI1 or KLRI2.
      Cotransfection with KLRE1 was necessary for surface expression of the NK cell
      receptor chains KLRI1 and KLRI2 in 293T cells. Moreover, KLRE1 can be
      coimmunoprecipitated with KLRI1 or KLRI2 from transfected NK cell lines. By flow
      cytometry, KLRE1 and KLRI1 showed colinear expression on NK cells, suggesting
      surface expression as heterodimers. Unlike other killer cell lectin-like
      receptors, KLRE1/KLRI1 and KLRE1/KLRI2 heterodimers predominantly migrated as
      single chains in SDS-PAGE, indicating noncovalent association. KLRI1 was
      coimmunoprecipitated with the tyrosine phosphatase Src homology region 2 domain
      containing phosphatase 1. In accordance with an inhibitory function, anti-HA Ab
      induced reduced killing of FcR-bearing targets by KLRI1-HA-transfected NK cell
      lines in a redirected cytotoxicity assay. Reciprocally, KLRI2-HA transfectants
      displayed increased killing in this assay. Finally, Ab to KLRE1 induced
      inhibition in KLRI1-transfected cells but increased cytotoxicity in KLRI2
      transfectants, demonstrating that KLRE/I1 is a functional inhibitory heterodimer
      in NK cells, whereas KLRE/I2 is an activating heterodimeric receptor.

PMID- 18713989
TI  - Human anti-IgG1 hinge autoantibodies reconstitute the effector functions of
      proteolytically inactivated IgGs.
AB  - A number of proteases of potential importance to human physiology possess the
      ability to selectively degrade and inactivate Igs. Proteolytic cleavage within
      and near the hinge domain of human IgG1 yielded products including Fab and
      F(ab')(2) possessing full Ag binding capability but absent several functions
      needed for immune destruction of cellular pathogens. In parallel experiments, we
      showed that the same proteolytically generated Fabs and F(ab')(2)s become self
      Ags that were widely recognized by autoantibodies in the human population.
      Binding analyses using various Fab and F(ab')(2), as well as single-chain peptide
      analogues, indicated that the autoantibodies targeted the newly exposed sequences
      where proteases cleave the hinge. The point of cleavage may be less of a
      determinant for autoantibody binding than the exposure of an otherwise cryptic
      stretch of hinge sequence. It was noted that the autoantibodies possessed an
      unusually high proportion of the IgG3 isotype in contrast to Abs induced against
      foreign immunogens in the same human subjects. In light of the recognized potency
      of IgG3 effector mechanisms, we adopted a functional approach to determine
      whether human anti-hinge (HAH) autoantibodies could reconstitute the (missing) Fc
      region effector functions to Fab and F(ab')(2). Indeed, in in vitro cellular
      assays, purified HAH autoantibodies restored effector functions to F(ab')(2) in
      both Ab-dependent cellular cytotoxicity and complement-dependent cytotoxicity
      assays. The results indicate that HAH autoantibodies selectively bind to
      proteolytically cleaved IgGs and can thereby provide a surrogate Fc domain to
      reconstitute cell lytic functions.

PMID- 18713990
TI  - OX40/OX40L costimulation affects induction of Foxp3+ regulatory T cells in part
      by expanding memory T cells in vivo.
AB  - OX40 is a member of the TNFR superfamily and has potent T cell costimulatory
      activities. OX40 also inhibits the induction of Foxp3(+) regulatory T cells
      (Tregs) from T effector cells, but the precise mechanism of such inhibition
      remains unknown. In the present study, we found that CD4(+) T effector cells from
      OX40 ligand-transgenic (OX40Ltg) mice are highly resistant to TGF-beta mediated
      induction of Foxp3(+) Tregs, whereas wild-type B6 and OX40 knockout CD4(+) T
      effector cells can be readily converted to Foxp3(+) T cells. We also found that
      CD4(+) T effector cells from OX40Ltg mice are heterogeneous and contain a large
      population of CD44(high)CD62L(-) memory T cells. Analysis of purified OX40Ltg
      naive and memory CD4(+) T effector cells showed that memory CD4(+) T cells not
      only resist the induction of Foxp3(+) T cells but also actively suppress the
      conversion of naive CD4(+) T effector cells to Foxp3(+) Tregs. This suppression
      is mediated by the production of IFN-gamma by memory T cells but not by cell-cell
      contact and also involves the induction of T-bet. Importantly, memory CD4(+) T
      cells have a broad impact on the induction of Foxp3(+) Tregs regardless of their
      origins and Ag specificities. Our data suggest that one of the mechanisms by
      which OX40 inhibits the induction of Foxp3(+) Tregs is by inducing memory T cells
      in vivo. This finding may have important clinical implications in tolerance
      induction to transplanted tissues.

PMID- 18713991
TI  - Myelin-reactive type B T cells and T cells specific for low-affinity MHC-binding
      myelin peptides escape tolerance in HLA-DR transgenic mice.
AB  - Genes of the MHC show the strongest genetic association with multiple sclerosis
      (MS), but the underlying mechanisms have remained unresolved. In this study, we
      asked whether the MS-associated MHC class II molecules, HLA-DRB1*1501, HLA
      DRB5*0101, and HLA-DRB1*0401, contribute to autoimmune CNS demyelination by
      promoting pathogenic T cell responses to human myelin basic protein (hMBP), using
      three transgenic (Tg) mouse lines expressing these MHC molecules. Unexpectedly,
      profound T cell tolerance to the high-affinity MHC-binding hMBP82-100 epitope was
      observed in all Tg mouse lines. T cell tolerance to hMBP82-100 was abolished upon
      back-crossing the HLA-DR Tg mice to MBP-deficient mice. In contrast, T cell
      tolerance was incomplete for low-affinity MHC-binding hMBP epitopes. Furthermore,
      hMBP82-100-specific type B T cells escaped tolerance in HLA-DRB5*0101 Tg mice.
      Importantly, T cells specific for low-affinity MHC-binding hMBP epitopes and
      hMBP82-100-specific type B T cells were highly encephalitogenic. Collectively,
      the results show that MS-associated MHC class II molecules are highly efficient
      at inducing T cell tolerance to high-affinity MHC-binding epitope, whereas
      autoreactive T cells specific for the low-affinity MHC-binding epitopes and type
      B T cells can escape the induction of T cell tolerance and may promote MS.

PMID- 18713992
TI  - The relative efficiency of acquisition of MHC:peptide complexes and cross
      presentation depends on dendritic cell type.
AB  - Intercellular exchange of MHC molecules has been reported between many cells,
      including professional and nonprofessional APCs. This phenomenon may contribute
      to T cell immunity to pathogens. In this study, we addressed whether the transfer
      of MHC class I:peptide complexes between cells plays a role in T cell responses
      and compare this to conventional cross-presentation. We observed that dsRNA
      matured bone marrow-derived dendritic cells (BMDCs) acquired peptide:MHC
      complexes from other BMDCs either pulsed with OVA(257-264) peptide, soluble OVA,
      or infected with a recombinant adenovirus expressing OVA. In addition, BMDCs were
      capable of acquiring MHC:peptide complexes from epithelial cells. Spleen-derived
      CD8alpha(+) and CD8alpha(-) dendritic cells (DCs) also acquired MHC:peptide
      complexes from BMDCs pulsed with OVA(257-264) peptide. However, the efficiency of
      acquisition by these ex vivo derived DCs is much lower than acquisition by BMDC.
      In all cases, the acquired MHC:peptide complexes were functional in that they
      induced Ag-specific CD8(+) T cell proliferation. The efficiency of MHC transfer
      was compared with cross-presentation for splenic CD8alpha(+) and CD8alpha(-) as
      well as BMDCs. CD8alpha(+) DCs were more efficient at inducing T cell
      proliferation when they acquired Ag via cross-presentation, the opposite was
      observed for BMDCs and splenic CD8alpha(-) DCs. We conclude from these
      observations that the relative efficiency of MHC transfer vs cross-presentation
      differs markedly between different DC subsets.

PMID- 18713993
TI  - Anergy in memory CD4+ T cells is induced by B cells.
AB  - Induction of tolerance in memory T cells has profound implications in the
      treatment of autoimmune diseases and transplant rejection. Previously, we
      reported that the presentation of low densities of agonist peptide/MHC class II
      complexes induced anergy in memory CD4(+) T cells. In the present study, we
      address the specific interaction of different types of APCs with memory CD4(+) T
      cells. A novel ex vivo anergy assay first suggested that B cells induce anergy in
      memory T cells, and an in vivo cell transfer assay further confirmed those
      observations. We demonstrated that B cells pulsed with defined doses of Ag
      anergize memory CD4 cells in vivo. We established that CD11c(+) dendritic cells
      do not contribute to anergy induction to CD4 memory T cells, because diphtheria
      toxin receptor-transgenic mice that were conditionally depleted of dendritic
      cells optimally induced anergy in memory CD4(+) T cells. Moreover, B cell
      deficient muMT mice did not induce anergy in memory T cells. We showed that B2
      follicular B cells are the specific subpopulation of B cells that render memory T
      cells anergic. Furthermore, we present data showing that anergy in this system is
      mediated by CTLA-4 up-regulation on T cells. This is the first study to
      demonstrate formally that B cells are the APCs that induce anergy in memory
      CD4(+) T cells.

PMID- 18713994
TI  - A unique role for the lambda5 nonimmunoglobulin tail in early B lymphocyte
      development.
AB  - Precursor BCR (pre-BCR) signaling governs proliferation and differentiation of
      pre-B cells during B lymphocyte development. However, it is controversial as to
      which parts of the pre-BCR, which is composed of Igmu H chain, surrogate L chain
      (SLC), and Igalpha-Igbeta, are important for signal initiation. Here, we show in
      transgenic mice that the N-terminal non-Ig-like (unique) tail of the surrogate L
      chain component lambda5 is critical for enhancing pre-BCR-induced proliferation
      signals. Pre-BCRs with a mutated lambda5 unique tail are still transported to the
      cell surface, but they deliver only basal signals that trigger survival and
      differentiation of pre-B cells. Further, we demonstrate that the positively
      charged residues of the lambda5 unique tail, which are required for pre-BCR self
      oligomerization, can also mediate binding to stroma cell-associated self-Ags,
      such as heparan sulfate. These findings establish the lambda5 unique tail as a
      pre-BCR-specific autoreactive signaling motif that could increase the size of the
      primary Ab repertoire by selectively expanding pre-B cells with functional Igmu H
      chains.

PMID- 18713995
TI  - The suppression of murine lupus by a tolerogenic peptide involves foxp3
      expressing CD8 cells that are required for the optimal induction and function of
      foxp3-expressing CD4 cells.
AB  - A peptide, designated human CDR1 (hCDR1), that is based on the CDR1 of an anti
      DNA Ab ameliorates systemic lupus erythematosus (SLE) in murine models via the
      induction of CD4(+)CD25(+) regulatory T cells (Tregs). In the present study, the
      involvement of CD8 Tregs in the mode of action of hCDR1 was investigated in SLE
      afflicted (NZB x NZW)F1 mice and in SJL mice following immunization with the
      lupus-inducing anti-DNA mAb that bears a common Id, 16/6Id. Treatment with hCDR1
      up-regulated Foxp3-expressing CD8(+)CD28(-) Tregs in association with clinical
      amelioration of lupus manifestations. Furthermore, the in vivo depletion of the
      latter cells diminished the clinical improvement and the inhibitory effects of
      hCDR1 on the secretion of IFN-gamma and resulted in the up-regulation of IL-10.
      However, the stimulatory effect of hCDR1 on the secretion of TGF-beta was not
      affected by the CD8 Tregs. In the absence of CD8 Tregs, CD4(+)CD25(+) Tregs were
      unable to expand in the hCDR1-treated mice, and the expression of Foxp3 was
      reduced, thereby interfering further with the suppressive function of
      CD4(+)CD25(+) Tregs as determined in the in vitro assays. However, CD8 cells from
      hCDR1-treated mice that were adoptively transferred into SLE-afflicted mice led
      to up-regulation of CD4(+)CD25(+) cells with intensified Foxp3 expression in the
      recipient mice. Thus, a functional link between two subsets of Tregs is
      demonstrated in which CD8(+)CD28(-) Tregs are required for both the optimal
      expansion and function of lupus ameliorating hCDR1-induced CD4(+)CD25(+) Tregs.

PMID- 18713996
TI  - Synoviocyte innate immune responses: I. Differential regulation of interferon
      responses and the JNK pathway by MAPK kinases.
AB  - JNK is a key regulator of matrix metalloproteinase production in rheumatoid
      arthritis. It is regulated by two upstream kinases known as MKK4 and MKK7.
      Previous studies demonstrated that only MKK7 is required for cytokine-mediated
      JNK activation and matrix metalloproteinase expression in cultured fibroblast
      like synoviocytes (FLS). However, the functions of MKK4 and MKK7 in synoviocyte
      innate immune responses have not been determined. TNF, peptidoglycan (PGN), and
      LPS stimulation led to higher and more prolonged MKK7 phosphorylation compared
      with MKK4 in FLS. However, this pattern was reversed in poly(I-C) stimulated
      cells. siRNA knockdown studies showed that TNF, PGN, and LPS-induced JNK and c
      Jun phosphorylation are MKK7 dependent, while poly(I-C) responses require both
      MKK4 and MKK7. Poly(I-C)-induced expression of IP-10, RANTES, and IFN-beta mRNA
      was decreased in MKK4- or MKK7-deficient FLS. However, MKK4 and MKK7 deficiency
      did not affect phosphorylation of IkappaB kinase-related kinases in the TLR3
      signaling pathway. MKK7, but not MKK4 deficiency, significantly decreased poly(I
      C)-mediated IRF3 dimerization, DNA binding, and IFN-sensitive response element
      mediated gene transcription. These results were mimicked by the JNK inhibitor
      SP600125, indicating that JNK can directly phosphorylate IRF3. In contrast,
      deficiency of either MKK4 or MKK7 decreased AP-1 transcriptional activity.
      Therefore, JNK is differentially regulated by MKK4 and MKK7 depending on the
      stimulus. MKK7 is the primary activator of JNK in TNF, LPS, and PGN responses.
      However, TLR3 requires both MKK4 and MKK7, with the former activating c-Jun and
      the latter activating both c-Jun and IRF3 through JNK-dependent mechanisms.

PMID- 18713997
TI  - Colocalization of antigen-specific B and T cells within ectopic lymphoid tissue
      following immunization with exogenous antigen.
AB  - Chronic inflammation promotes the formation of ectopic lymphoid tissue
      morphologically resembling secondary lymphoid tissues, though it is unclear
      whether this is a location where Ag-specific immune responses develop or merely a
      site of lymphocyte accumulation. Ectopic lymphoid tissue formation is associated
      with many humoral autoimmune diseases, including lupus induced by
      tetramethylpecadentane in mice. We examined whether an immune response to 4
      hydroxy-3-nitrophenyl acetyl-keyhole limpet hemocyanin (NP-KLH) and NP-OVA
      develops within ectopic lymphoid tissue ("lipogranulomas") induced by
      tetramethylpecadentane in C57BL/6 mice. Following primary immunization, NP
      specific B cells bearing V186.2 and related heavy chains as well as lambda-light
      chains accumulated within ectopic lymphoid tissue. The number of anti-NP
      secreting B cells in the ectopic lymphoid tissue was greatly enhanced by
      immunization with NP-KLH. Remarkably, the H chain sequences isolated from
      individual lipogranulomas from these mice were diverse before immunization,
      whereas individual lipogranulomas from single immunized mice had unique oligo- or
      monoclonal populations of presumptive NP-specific B cells. H chain CDR sequences
      bore numerous replacement mutations, consistent with an Ag-driven and T cell
      mediated response. In mice adoptively transferred with OT-II or DO11 T cells,
      there was a striking accumulation of OVA-specific T cells in lipogranulomas after
      s.c. immunization with NP-OVA. The selective colocalization of proliferating, Ag
      specific T and B lymphocytes in lipogranulomas from tetramethylpecadentane
      treated mice undergoing primary immunization implicates ectopic lymphoid tissue
      as a site where Ag-specific humoral immune responses can develop. This has
      implications for understanding the strong association of humoral autoimmunity
      with lymphoid neogenesis, which may be associated with deficient censoring of
      autoreactive cells.

PMID- 18713998
TI  - Human invariant NKT cells display alloreactivity instructed by invariant TCR-CD1d
      interaction and killer Ig receptors.
AB  - Invariant NKT (iNKT) cells are a subset of highly conserved immunoregulatory T
      cells that modify a variety of immune responses, including alloreactivity.
      Central to their function is the interaction of the invariant TCR with
      glycosphingolipid (GSL) ligands presented by the nonpolymorphic MHC class I
      molecule CD1d and their ability to secrete rapidly large amounts of
      immunomodulatory cytokines when activated. Whether iNKT cells, like NK and
      conventional T cells, can directly display alloreactivity is not known. We show
      in this study that human iNKT cells and APC can establish a direct cross-talk
      leading to preferential maturation of allogeneic APC and a considerably higher
      reactivity of iNKT cells cultured with allogeneic rather that autologous APC.
      Although the allogeneic activation of iNKT cells is invariant TCR-CD1d
      interaction-dependent, GSL profiling suggests it does not involve the recognition
      of disparate CD1d/GSL complexes. Instead, we show that contrary to previous
      reports, iNKT cells, like NK and T cells, express killer Ig receptors at a
      frequency similar to that of conventional T cells and that iNKT cell allogeneic
      activation requires up-regulation and function of activating killer Ig receptors.
      Thus, iNKT cells can display alloreactivity, for which they use mechanisms
      characteristic of both NK and conventional T cells.

PMID- 18713999
TI  - Apoptotic cells induce immunosuppression through dendritic cells: critical roles
      of IFN-gamma and nitric oxide.
AB  - Apoptotic cells induce immunosuppression through unknown mechanisms. To identify
      the underlying molecular mediators, we examined how apoptotic cells induce
      immunoregulation by dendritic cells (DC). We found that administration of DC
      exposed to apoptotic cells (DC(ap)) strongly inhibited the expansion of
      lymphocytes in draining lymph nodes in vivo and the subsequent Ag-specific
      activation of these lymphocytes ex vivo. Unexpectedly, DC(ap) supported T cell
      activation to a similar extent as normal DC in vitro, leading to proliferation
      and IL-2 production, except that DC(ap) did not support T cell production of IFN
      gamma. Surprisingly, when DC(ap) were cocultured with normal DC, they completely
      lost their ability to support T cell activation, an effect reversed by anti-IFN
      gamma or inhibitors of inducible NO synthase (iNOS). As expected, exposure to
      apoptotic cells rendered DC(ap) capable of producing much more NO in response to
      exogenous IFN-gamma than normal DC. Furthermore, DC(ap) from iNOS(-/-) or IFN
      gammaR1(-/-) mice were not inhibitory in vitro or in vivo. Therefore, the IFN
      gamma-induced production of NO by apoptotic cell-sensitized DC plays a key role
      in apoptotic cell-mediated immunosuppression.

PMID- 18714000
TI  - IL-2, -7, and -15, but not thymic stromal lymphopoeitin, redundantly govern
      CD4+Foxp3+ regulatory T cell development.
AB  - Common gamma chain (gammac)-receptor dependent cytokines are required for
      regulatory T cell (Treg) development as gammac(-/-) mice lack Tregs. However, it
      is unclear which gammac-dependent cytokines are involved in this process.
      Furthermore, thymic stromal lymphopoietin (TSLP) has also been suggested to play
      a role in Treg development. In this study, we demonstrate that developing
      CD4(+)Foxp3(+) Tregs in the thymus express the IL-2Rbeta, IL-4Ralpha, IL-7Ralpha,
      IL-15Ralpha, and IL-21Ralpha chains, but not the IL9Ralpha or TSLPRalpha chains.
      Moreover, only IL-2, and to a much lesser degree IL-7 and IL-15, were capable of
      transducing signals in CD4(+)Foxp3(+) Tregs as determined by monitoring STAT5
      phosphorylation. Likewise, IL-2, IL-7, and IL-15, but not TSLP, were capable of
      inducing the conversion of CD4(+)CD25(+)Foxp3(-) thymic Treg progenitors into
      CD4(+)Foxp3(+) mature Tregs in vitro. To examine this issue in more detail, we
      generated IL-2Rbeta(-/-) x IL-7Ralpha(-/-) and IL-2Rbeta(-/-) x IL-4Ralpha(-/-)
      mice. We found that IL-2Rbeta(-/-) x IL-7Ralpha(-/-) mice were devoid of Tregs
      thereby recapitulating the phenotype observed in gammac(-/-) mice; in contrast,
      the phenotype observed in IL-2Rbeta(-/-) x IL-4Ralpha(-/-) mice was comparable to
      that seen in IL-2Rbeta(-/-) mice. Finally, we observed that Tregs from both IL-2(
      /-) and IL-2Rbeta(-/-) mice show elevated expression of IL-7Ralpha and IL
      15Ralpha chains. Addition of IL-2 to Tregs from IL-2(-/-) mice led to rapid down
      regulation of these receptors. Taken together, our results demonstrate that IL-2
      plays the predominant role in Treg development, but that in its absence the IL
      7Ralpha and IL-15Ralpha chains are up-regulated and allow for IL-7 and IL-15 to
      partially compensate for loss of IL-2.

PMID- 18714001
TI  - Tumor-induced CD11b+Gr-1+ myeloid cells suppress T cell sensitization in tumor
      draining lymph nodes.
AB  - Suppression of tumor-specific T cell sensitization is a predominant mechanism of
      tumor escape. To identify tumor-induced suppressor cells, we transferred spleen
      cells from mice bearing progressive MCA205 sarcoma into sublethally irradiated
      mice. These mice were then inoculated subdermally with tumor cells to stimulate T
      cell response in the tumor-draining lymph-node (TDLN). Tumor progression induced
      splenomegaly with a dramatic increase (22.1%) in CD11b(+)Gr-1(+) myeloid-derived
      suppressor cells (MDSC) compared with 2.6% of that in normal mice. Analyses of
      therapeutic effects by the adoptive immunotherapy revealed that the transfer of
      spleen cells from tumor-bearing mice severely inhibited the generation of tumor
      immune T cells in the TDLN. We further identified MDSC to be the dominant
      suppressor cells. However, cells of identical phenotype from normal spleens
      lacked the suppressive effects. The suppression was independent of CD4(+)CD25(+)
      regulatory T cells. Intracellular IFN-gamma staining revealed that the transfer
      of MDSC resulted in a decrease in numbers of tumor-specific CD4(+) and CD8(+) T
      cells. Transfer of MDSC from MCA207 tumor-bearing mice also suppressed the MCA205
      immune response indicating a lack of immunologic specificity. Further analyses
      demonstrated that MDSC inhibited T cell activation that was triggered either by
      anti-CD3 mAb or by tumor cells. However, MDSC did not suppress the function of
      immune T cells in vivo at the effector phase. Our data provide the first evidence
      that the systemic transfer of MDSC inhibited and interfered with the
      sensitization of tumor-specific T cell responses in the TDLN.

PMID- 18714002
TI  - Synthetic Peptide dendrimers block the development and expression of experimental
      allergic encephalomyelitis.
AB  - Multiple Ag peptides (MAPs) containing eight proteolipid protein (PLP)(139-151)
      peptides arranged around a dendrimeric branched lysine core were used to
      influence the expression and development of relapsing experimental allergic
      encephalomyelitis (EAE) in SJL mice. The PLP(139-151) MAPs were very efficient
      agents in preventing the development of clinical disease when administered after
      immunization with the PLP(139-151) monomeric encephalitogenic peptide in CFA. The
      treatment effect with these MAPs was peptide specific; irrelevant multimeric
      peptides such as guinea pig myelin basic protein GPBP(72-84) MAP (a dendrimeric
      octamer composed of the 72-84 peptide) and PLP(178-191) MAP (a dendrimeric
      octamer composed of the PLP(178-191) peptide) had no treatment effect on PLP(139
      151)-induced EAE. PLP(139-151) MAP treatment initiated after clinical signs of
      paralysis also altered the subsequent course of EAE; it limited developing signs
      of paralysis and effectively limited the severity and number of disease relapses
      in MAP-treated mice over a 60-day observation period. PLP(139-151) MAP therapy
      initiated before disease onset acts to limit the numbers of Th17 and IFN-gamma
      producing cells that enter into the CNS. However, Foxp3(+) cells entered the CNS
      in numbers equivalent for nontreated and PLP(139-151) MAP-treated animals. The
      net effect of PLP(139-151) MAP treatment dramatically increases the ratio of
      Foxp3(+) cells to Th17 and IFN-gamma-producing cells in the CNS of PLP(139-151)
      MAP-treated animals.

PMID- 18714003
TI  - Two macrophage colony-stimulating factor genes exist in fish that differ in gene
      organization and are differentially expressed.
AB  - Mammalian macrophage CSF (MCSF; CSF-1) is the primary regulator of the
      mononuclear phagocyte lineage. We, for the first time, report the complete
      sequencing of five MCSF cDNAs from three fish species, rainbow trout, zebrafish,
      and goldfish. Despite the difference in the lengths of the MCSF transcripts, all
      of the fish MCSF molecules encode a signal peptide, a CSF-1 domain, a
      transmembrane domain, and an intracellular region. Each fish MCSF gene has a
      unique exon/intron structure. The primordial MCSF gene may have had a nine
      exon/eight intron structure. In this model, insertion of an intron in exon 6 in
      primitive fish created the fish type I MCSF, while the loss of this exon or part
      of the original exon 6 created the fish type II MCSF. Investigation of
      alternative splicing variants in trout suggests that no mammalian equivalent
      splice variants exist. The two trout MCSF genes are differentially expressed in
      vivo and contributed differently to the high-level expression of MCSF in spleen
      and head kidney. In contrast to the up-regulation of MCSF by PMA in mammals, in
      trout MCSF1 expression is down-regulated by PMA treatment. As in mammals,
      recombinant trout MCSF1 can promote the growth of head kidney leukocytes, and it
      up-regulates the expression of CXCR3 in head kidney macrophages, with the latter
      suggesting a role of MCSF in the trafficking of macrophages to sites of
      inflammation or injury where the CXCR3 ligands are expressed. Thus MCSF has an
      important role in the immune system of fish as in mammals.

PMID- 18714004
TI  - In vivo suppression of naive CD4 T cell responses by IL-2- and antigen-stimulated
      T lymphocytes in the absence of APC competition.
AB  - After stimulation, T cells enter a transient refractory period, promoted by IL-2,
      during which they are resistant to re-stimulation. We previously demonstrated
      that these IL-2- and Ag-stimulated refractory T cells are able to suppress the Ag
      induced proliferation of naive T cells in vitro. We show here that, after
      adoptive transfer, these T cells are also able to suppress naive T cell
      proliferation in vivo. More interestingly, potently suppressive T cells can be
      generated directly in vivo by stimulation with Ag and supplemental IL-2. The
      activity of the suppressive cells is dose dependent, and the suppressor and
      suppressed T cells need not be restricted to the same MHC or Ag. Similar to its
      role in promoting T cell-mediated suppression in vitro, IL-2 is critical for the
      induction of suppressive activity in activated T cells in vivo. Supplemental IL
      2, however, cannot overcome the suppressive activity in target T cells,
      indicating that suppression is not mediated by competition for this cytokine.
      Although the activated T cells block naive T cell proliferation, the naive cells
      do engage Ag and up-regulate the CD25 and CD69 activation markers after
      stimulation. Therefore, activated T cells stimulated in the presence of IL-2
      develop MHC- and Ag-unrestricted suppressive activity. These results provide a
      new mechanism for competition among CD4(+) T lymphocytes, in which initial waves
      of responding T cells may inhibit subsequently recruited naive T cells. They
      further suggest a novel negative feedback loop limiting the expansion of T cell
      responses that may be present during vigorous immune responses or after IL-2
      immunotherapy.

PMID- 18714005
TI  - A polypyrimidine tract-binding protein-dependent pathway of mRNA stability
      initiates with CpG activation of primary B cells.
AB  - The mRNA encoding CD154, a critical protein involved in both humoral and cell
      mediated immune responses, is regulated at the posttranscriptional level by the
      binding of complex I, a polypyrimidine tract-binding (PTB) protein-containing
      complex, which acts to increase message stability at late times of activation.
      Our current work focuses on analyzing a similar complex in B cells, designated B
      cpx I, which is increased in B cells activated by CpG engagement of the TLR9
      receptor but not by activation through CD40. Expression profiling of transcripts
      from primary B cells identified 31 mRNA transcripts with elevated PTB binding
      upon activation. Two of these transcripts, Rab8A and cyclin D(2), contained
      binding sites for B-cpx I in their 3' untranslated regions (UTRs). Analysis of
      turnover of endogenous Rab8A transcript in B cells revealed that like CD154, the
      mRNA half-life increased following activation and insertion of the Rab8A B-cpx I
      binding site into a heterologous transcript led to a 3-fold increase in
      stability. Also, short hairpin RNA down-regulation of PTB resulted in a
      corresponding decrease in Rab8A mRNA half-life. Overall these data strongly
      support a novel pathway of mRNA turnover that is expressed both in T cells and B
      cells and depends on the formation of a PTB-containing stability complex in
      response to cellular activation.

PMID- 18714006
TI  - Transcription factor-dependent chromatin remodeling of Il18r1 during Th1 and Th2
      differentiation.
AB  - The IL-18Ralpha-chain is expressed on Th1 but not Th2 cells. We have recently
      shown that Stat4 is an important component of programming the Il18r1 locus
      (encoding IL-18Ralpha) for maximal expression in Th1 cells. Il18r1 is
      reciprocally repressed during Th2 development. In this report, we demonstrate the
      establishment of DH patterns that are distinct among undifferentiated CD4 T, Th1,
      and Th2 cells. Stat6 is required for the repression of Il18r1 expression and in
      Stat6-deficient Th2 cultures, mRNA levels, histone acetylation, and H3K4
      methylation levels are intermediate between levels observed in Th1 and Th2 cells.
      Despite the repressive effects of IL-4 during Th2 differentiation, we observed
      only modest binding of Stat6 to the Il18r1 locus. In contrast, we observed robust
      GATA-3 binding to a central region of the locus where DNase hypersensitivity
      sites overlapped with conserved non-coding sequences in Il18r1 introns. Ectopic
      expression of GATA-3 in differentiated Th1 cells repressed Il18r1 mRNA and
      surface expression of IL-18Ralpha. These data provide further mechanistic insight
      into transcription factor-dependent establishment of Th subset-specific patterns
      of gene expression.

PMID- 18714007
TI  - Hemopoietic cell expression of the chemokine decoy receptor D6 is dynamic and
      regulated by GATA1.
AB  - D6 scavenges inflammatory chemokines and is essential for the regulation of
      inflammatory and immune responses. Mechanisms explaining the cellular basis for
      D6 function have been based on D6 expression by lymphatic endothelial cells. In
      this study, we demonstrate that functional D6 is also expressed by murine and
      human hemopoietic cells and that this expression can be regulated by pro- and
      anti-inflammatory agents. D6 expression was highest in B cells and dendritic
      cells (DCs). In myeloid cells, LPS down-regulated expression, while TGF-beta up
      regulated expression. Activation of T cells with anti-CD3 and soluble CD28 up
      regulated mRNA expression 20-fold, while maturation of human macrophage and
      megakaryocyte precursors also up-regulated D6 expression. Competition assays
      demonstrated that chemokine uptake was D6 dependent in human leukocytes, whereas
      mouse D6-null cells failed to uptake and clear inflammatory chemokines.
      Furthermore, we present evidence indicating that D6 expression is GATA1
      dependent, thus explaining D6 expression in myeloid progenitor cells, mast cells,
      megakaryocytes, and DCs. We propose a model for D6 function in which leukocytes,
      within inflamed sites, activate D6 expression and thus trigger resolution of
      inflammatory responses. Our data on D6 expression by circulating DCs and B cells
      also suggest alternative roles for D6, perhaps in the coordination of innate and
      adaptive immune responses. These data therefore alter our models of in vivo D6
      function and suggest possible discrete, and novel, roles for D6 on lymphatic
      endothelial cells and leukocytes.

PMID- 18714008
TI  - EBF1 is essential for B-lineage priming and establishment of a transcription
      factor network in common lymphoid progenitors.
AB  - Development of B-lymphoid cells in the bone marrow is a process under strict
      control of a hierarchy of transcription factors. To understand the development of
      a B-lymphoid-restricted functional network of transcription factors, we have
      investigated the cell autonomous role of the transcription factor EBF1 in early B
      cell development. This revealed that even though transplanted EBF1-deficient
      fetal liver cells were able to generate common lymphoid progenitors (CLPs) as
      well as B220(+)CD43(+)AA4.1(+) candidate precursor B cells, none of these
      populations showed signs of B lineage priming. The isolated CLPs were able to
      generate T lymphocytes in vitro supporting the idea that the phenotype of EBF1
      deficient mice is restricted to the development of the B lineage. Furthermore,
      EBF deficient CLPs displayed a reduction in Ig H chain recombination as compared
      with their wild-type counterpart and essentially lacked transcription of B
      lineage-associated genes. Among the genes displaying reduced expression in the
      EBF1 deficient CLPs were the transcription factors Pax5, Pou2af1 (OcaB), and
      FoxO1 that all appear to be direct genetic targets for EBF1 because their
      promoters contained functional binding sites for this factor. This leads us to
      suggest that EBF1 regulates a transcription factor network crucial for B lineage
      commitment.

PMID- 18714009
TI  - Rap1b regulates B cell development, homing, and T cell-dependent humoral
      immunity.
AB  - Rap1 is a small GTPase that belongs to Ras superfamily. This ubiquitously
      expressed GTPase is a key regulator of integrin functions. Rap1 exists in two
      isoforms: Rap1a and Rap1b. Although Rap1 has been extensively studied, its
      isoform-specific functions in B cells have not been elucidated. In this study,
      using gene knockout mice, we show that Rap1b is the dominant isoform in B cells.
      Lack of Rap1b significantly reduced the absolute number of B220(+)IgM(-) pro/pre
      B cells and B220(+)IgM(+) immature B cells in bone marrow. In vitro culture of
      bone marrow-derived Rap1b(-/-) pro/pre-B cells with IL-7 showed similar
      proliferation levels but reduced adhesion to stromal cell line compared with wild
      type. Rap1b(-/-) mice displayed reduced splenic marginal zone (MZ) B cells, and
      increased newly forming B cells, whereas the number of follicular B cells was
      normal. Functionally, Rap1b(-/-) mice showed reduced T-dependent but normal T
      independent humoral responses. B cells from Rap1b(-/-) mice showed reduced
      migration to SDF-1, CXCL13 and in vivo homing to lymph nodes. MZ B cells showed
      reduced sphingosine-1-phosphate-induced migration and adhesion to ICAM-1.
      However, absence of Rap1b did not affect splenic B cell proliferation, BCR
      mediated activation of Erk1/2, p38 MAPKs, and AKT. Thus, Rap1b is crucial for
      early B cell development, MZ B cell homeostasis and T-dependent humoral immunity.

PMID- 18714010
TI  - Molecular requirements for MHC class II alpha-chain engagement and allelic
      discrimination by the bacterial superantigen streptococcal pyrogenic exotoxin C.
AB  - Superantigens (SAgs) are microbial toxins that bind to both TCR beta-chain
      variable domains (Vbetas) and MHC class II molecules, resulting in the activation
      of T cells in a Vbeta-specific manner. It is now well established that different
      isoforms of MHC II molecules can play a significant role in the immune response
      to bacterial SAgs. In this work, using directed mutational studies in conjunction
      with functional analyses, we provide a complete functional map of the low
      affinity MHC II alpha-chain binding interface of the SAg streptococcal pyrogenic
      exotoxin C (SpeC) and identify a functional epitope in the beta-barrel domain
      that is required for the activation of T cells. Using cell lines that exclusively
      express individual MHC II isoforms, our studies provide a molecular basis for the
      selectivity of SpeC-MHC II recognition, and provide one mechanism by how SAgs are
      capable of distinguishing between different MHC II alleles.

PMID- 18714011
TI  - Contribution of mutation, recombination, and gene conversion to chicken MHC-B
      haplotype diversity.
AB  - The Mhc is a highly conserved gene region especially interesting to geneticists
      because of the rapid evolution of gene families found within it. High levels of
      Mhc genetic diversity often exist within populations. The chicken Mhc is the
      focus of considerable interest because of the strong, reproducible infectious
      disease associations found with particular Mhc-B haplotypes. Sequence data for
      Mhc-B haplotypes have been lacking thereby hampering efforts to systematically
      resolve which genes within the Mhc-B region contribute to well-defined Mhc-B
      associated disease responses. To better understand the genetic factors that
      generate and maintain genomic diversity in the Mhc-B region, we determined the
      complete genomic sequence for 14 Mhc-B haplotypes across a region of 59 kb that
      encompasses 14 gene loci ranging from BG1 to BF2. We compared the sequences using
      alignment, phylogenetic, and genome profiling methods. We identified gene
      structural changes, synonymous and non-synonymous polymorphisms, insertions and
      deletions, and allelic gene rearrangements or exchanges that contribute to
      haplotype diversity. Mhc-B haplotype diversity appears to be generated by a
      number of mutational events. We found evidence that some Mhc-B haplotypes are
      derived by whole- and partial-allelic gene conversion and homologous reciprocal
      recombination, in addition to nucleotide mutations. These data provide a
      framework for further analyses of disease associations found among these 14
      haplotypes and additional haplotypes segregating and evolving in wild and
      domesticated populations of chickens.

PMID- 18714012
TI  - Congenic analysis of the NKT cell control gene Nkt2 implicates the peroxisomal
      protein Pxmp4.
AB  - Type 1 NKT cells play a critical role in controlling the strength and character
      of adaptive and innate immune responses. We have previously reported deficiencies
      in the numbers and function of NKT cells in the NOD mouse strain, which is a well
      validated model of type 1 diabetes and systemic lupus erythematosus. Genetic
      control of thymic NKT cell numbers was mapped to two linkage regions: Nkt1 on
      distal chromosome 1 and Nkt2 on chromosome 2. Herein, we report the production
      and characterization of a NOD.Nkrp1(b).Nkt2b(b) congenic mouse strain, which has
      increased thymic and peripheral NKT cells, a decreased incidence of type 1
      diabetes, and enhanced cytokine responses in vivo and increased proliferative
      responses in vitro following challenge with alpha-galactosylceramide. The 19
      highly differentially expressed candidate genes within the congenic region
      identified by microarray expression analyses included Pxmp4. This gene encodes a
      peroxisome-associated integral membrane protein whose only known binding partner
      is Pex19, an intracellular chaperone and component of the peroxisomal membrane
      insertion machinery encoded by a candidate for the NKT cell control gene Nkt1.
      These findings raise the possibility that peroxisomes play a role in modulating
      glycolipid availability for CD1d presentation, thereby influencing NKT cell
      function.

PMID- 18714013
TI  - The major bactericidal activity of human seminal plasma is zinc-dependent and
      derived from fragmentation of the semenogelins.
AB  - One of the major roles of seminal plasma is to provide antimicrobial protection
      for the spermatozoa in the female reproductive tract. We found that the
      bactericidal activity of seminal plasma was highest after resolution of the
      seminal clot and that this antibacterial activity subsequently became greatly
      diminished. The antibacterial activity was derived from peptides generated by
      fragmentation of the semenogelins while the semenogelin holoproteins displayed no
      antibacterial activity. After ejaculation the semenogelin-derived peptides were
      fragmented to smaller and smaller fragments over time and thereby lost
      antibacterial activity. This paralleled the loss of antibacterial activity of
      whole seminal plasma both in vitro and after sexual intercourse. Moreover, the
      antibacterial activity of the semenogelin-derived peptides generated in seminal
      plasma was strictly zinc-dependent both at neutral and low pH. These data provide
      novel roles for the resolution of seminal clots and for the high zinc
      concentration in human seminal plasma.

PMID- 18714014
TI  - Combined triggering of dendritic cell receptors results in synergistic activation
      and potent cytotoxic immunity.
AB  - Elimination of malignant cells and intracellular infections involves
      collaboration between CTLs and Th1 inflammation. Dendritic cells drive this
      response via costimulation and cytokines. We have defined key signals required
      for the exponential expansion of specific CD8(+) T cells in vivo in mice.
      Immunization with two or more TLR agonists, anti-CD40, IFN-gamma, and surfactant
      were sufficient to drive unprecedented levels of CD8 response to peptide or
      protein Ag and highly polarized Th1 CD4 responses. CD40 signaling was required
      for CD8 expansion but could be provided by a concomitant CD4 Th response in place
      of anti-CD40. Triggering of these pathways activated migration and activation of
      myeloid and plasmacytoid dendritic cells and secretion of IL-12. Cross
      presentation can thus be exploited to induce potent cytotoxic responses and long
      term memory to peptide/protein Ags. When combined with a tumor-associated peptide
      from tyrosinase-related protein 2, our combined adjuvant approach effectively
      halted tumor growth in an in vivo melanoma model and was more effective than anti
      CD40 and a single TLR agonist. Antitumor immunity was associated with long-lived
      effector memory CD8 cells specific for the naturally processed and presented
      tumor Ag, and tumor protection was partially but not entirely dependent on CD8 T
      cells. This flexible strategy is more effective than existing adjuvants and
      provides a technological platform for rapid vaccine development.

PMID- 18714015
TI  - B lymphocyte activation by coinfection prevents immune control of friend virus
      infection.
AB  - Although the adaptive immune response almost invariably fails to completely
      eliminate retroviral infections, it can exert significant protection from disease
      and long-term control of viral replication. Friend virus (FV), a mouse
      retrovirus, causes persistent infection in all strains of mice and
      erythroleukaemia in susceptible strains, the course of which can be strongly
      influenced by both genetic and extrinsic factors. In this study we examine the
      impact of coinfection on the requirements for immune control of FV infection. We
      show that congenic C57BL/6 mice, in which the introduction of an allele of the
      Friend virus susceptibility 2 gene provides the potential for FV-induced leukemia
      development, effectively resist FV infection, and both T cell- and Ab-dependent
      mechanisms contribute to their resistance. However, we further demonstrate that
      coinfection with lactate dehydrogenase-elevating virus (LDV) renders these
      otherwise immunocompetent mice highly susceptible to FV infection and subsequent
      disease. The presence of LDV delays induction of FV-specific neutralizing Abs and
      counteracts the protective contribution of adaptive immunity. Importantly, the
      disease-enhancing effect of LDV coinfection requires the presence of a polyclonal
      B cell repertoire and is reproduced by direct polyclonal B cell activation. Thus,
      immune activation by coinfecting pathogens or their products can contribute to
      the pathogenicity of retroviral infection.

PMID- 18714016
TI  - Enhanced resistance of restraint-stressed mice to sepsis.
AB  - Sepsis remains a major health concern across the world. The effects of stress on
      host resistance to sepsis are still not very clear. To explore the effects of
      chronic stress on sepsis(') we examined the impact of restraint stress on the
      resistance of mice to sepsis. Interestingly, it was found that restraint stress
      enhanced the antisepsis resistance of mice and the concentrations of the
      proinflammatory cytokines IL-1, IL-6, IL-12, and TNF-alpha in the blood of
      stressed mice were dramatically reduced post Escherichia coli infection or LPS
      treatment as compared with that of controls (p < 0.05). In addition, the mRNA
      expressions of glucocorticoid-induced leucine zipper (GILZ) were up-regulated in
      the spleen and peritoneal macrophages of mice receiving restraint stress or
      dexamethasone treatment. These results demonstrate that restraint stress enhances
      the resistance of mice to sepsis, supporting corticotherapy for sepsis and
      proposing restraint-stressed mouse as an animal model to elucidate mechanisms of
      stress-associated, antisepsis resistance.

PMID- 18714017
TI  - Adoptive transfer of gene-modified primary NK cells can specifically inhibit
      tumor progression in vivo.
AB  - NK cells hold great potential for improving the immunotherapy of cancer.
      Nevertheless, tumor cells can effectively escape NK cell-mediated apoptosis
      through interaction of MHC molecules with NK cell inhibitory receptors. Thus, to
      harness NK cell effector function against tumors, we used Amaxa gene transfer
      technology to gene-modify primary mouse NK cells with a chimeric single-chain
      variable fragment (scFv) receptor specific for the human erbB2 tumor-associated
      Ag. The chimeric receptor was composed of the extracellular scFv anti-erbB2 Ab
      linked to the transmembrane and cytoplasmic CD28 and TCR-zeta signaling domains
      (scFv-CD28-zeta). In this study we demonstrated that mouse NK cells gene-modified
      with this chimera could specifically mediate enhanced killing of an erbB2(+) MHC
      class I(+) lymphoma in a perforin-dependent manner. Expression of the chimera did
      not interfere with NK cell-mediated cytotoxicity mediated by endogenous NK
      receptors. Furthermore, adoptive transfer of gene-modified NK cells significantly
      enhanced the survival of RAG mice bearing established i.p. RMA-erbB2(+) lymphoma.
      In summary, these data suggest that use of genetically modified NK cells could
      broaden the scope of cancer immunotherapy for patients.

PMID- 18714018
TI  - IL-17A produced by gammadelta T cells plays a critical role in innate immunity
      against listeria monocytogenes infection in the liver.
AB  - IL-17A is originally identified as a proinflammatory cytokine that induces
      neutrophils. Although IL-17A production by CD4(+) Th17 T cells is well
      documented, it is not clear whether IL-17A is produced and participates in the
      innate immune response against infections. In the present report, we demonstrate
      that IL-17A is expressed in the liver of mice infected with Listeria
      monocytogenes from an early stage of infection. IL-17A is important in protective
      immunity at an early stage of listerial infection in the liver because IL-17A
      deficient mice showed aggravation of the protective response. The major IL-17A
      producing cells at the early stage were TCR gammadelta T cells expressing TCR
      Vgamma4 or Vgamma6. Interestingly, TCR gammadelta T cells expressing both IFN
      gamma and IL-17A were hardly detected, indicating that the IL-17A-producing TCR
      gammadelta T cells are distinct from IFN-gamma-producing gammadelta T cells,
      similar to the distinction between Th17 and Th1 in CD4(+) T cells. All the
      results suggest that IL-17A is a newly discovered effector molecule produced by
      TCR gammadelta T cells, which is important in innate immunity in the liver.

PMID- 18714019
TI  - TLR adaptor MyD88 is essential for pathogen control during oral toxoplasma gondii
      infection but not adaptive immunity induced by a vaccine strain of the parasite.
AB  - TLR adaptor MyD88 activation is important in host resistance to Toxoplasma gondii
      during i.p. infection, but the function of this signaling pathway during oral
      infection, in which mucosal immunity assumes a predominant role, has not been
      examined. In this study, we show that MyD88(-/-) mice fail to control the
      parasite and succumb within 2 wk of oral infection. Early during infection, T
      cell IFN-gamma production, recruitment of neutrophils and induction of p47 GTPase
      IGTP (Irgm3) in the intestinal mucosa were dependent upon functional MyD88.
      Unexpectedly, these responses were MyD88-independent later during acute
      infection. In particular, CD4(+) T cell IFN-gamma reached normal levels
      independently of MyD88, despite continued absence of IL-12 in these animals. The
      i.p. vaccination of MyD88(-/-) mice with an avirulent T. gondii uracil auxotroph
      elicited robust IFN-gamma responses and protective immunity to challenge with a
      high virulence T. gondii strain. Our results demonstrate that MyD88 is required
      to control Toxoplasma infection, but that the parasite can trigger adaptive
      immunity without the need for this TLR adaptor molecule.

PMID- 18714020
TI  - Teleost TLR22 recognizes RNA duplex to induce IFN and protect cells from
      birnaviruses.
AB  - TLR22 occurs exclusively in aquatic animals and its role is unknown. Herein we
      show that the fugu (Takifugu rubripes) (fg)TLR3 and fgTLR22 link the IFN-inducing
      pathway via the fg Toll-IL-1R homology domain-containing adaptor protein
      1(fgTICAM-1, or TRIF) adaptor in fish cells. fgTLR3 resides in endoplasmic
      reticulum and recognizes relatively short-sized dsRNA, whereas fgTLR22 recognizes
      long-sized dsRNA on the cell surface. On poly(I:C)-stimulated fish cells, both
      recruit fgTICAM-1, which in turn moves from the TLR to a cytoplasmic signalosome
      region. Thus, fgTICAM-1 acts as a shuttling platform for IFN signaling. When fish
      cells expressing fgTLR22 are exposed to dsRNA or aquatic dsRNA viruses, cells
      induce IFN responses to acquire resistance to virus infection. Thus, fish have a
      novel TICAM-1-coupling TLR that is distinct from the mammalian TLR3 in cellular
      localization, ligand selection, and tissue distribution. TLR22 may be a
      functional substitute of human cell-surface TLR3 and serve as a surveillant for
      infection with dsRNA virus to alert the immune system for antiviral protection in
      fish.

PMID- 18714021
TI  - Inchoate CD8+ T cell responses in neonatal mice permit influenza-induced
      persistent pulmonary dysfunction.
AB  - Influenza infection remains a significant cause of pulmonary morbidity and
      mortality worldwide, with the highest hospitalization and mortality rates
      occurring in infants and elder adults. The mechanisms inducing this considerable
      morbidity and mortality are largely unknown. To address this question, we
      established a neonatal mouse model of influenza infection to test the hypothesis
      that the immaturity of the neonatal immune system is responsible for the severe
      pulmonary disease observed in infants. Seven-day-old mice were infected with
      influenza A virus (H1N1) and allowed to mature. As adults, these mice showed
      enhanced airway hyperreactivity, chronic pulmonary inflammation, and diffuse
      emphysematous-type lesions in the lungs. The adaptive immune responses of the
      neonates were much weaker than those of adults. This insufficiency appeared to be
      in both magnitude and functionality and was most apparent in the CD8(+) T cell
      population. To determine the role of neonatal CD8(+) T cells in disease outcome,
      adult, naive CD8(+) T cells were adoptively transferred into neonates before
      infection. Neonatal mice receiving the adult CD8(+) T cells had significantly
      lower pulmonary viral titers and greatly improved pulmonary function as adults
      (airway resistance similar to SHAM). Additional adoptive transfer studies using
      adult CD8(+) T cells from IFN-gamma-deficient mice demonstrated the importance of
      IFN-gamma from CD8(+) T cells in controlling the infection and in determining
      disease outcome. Our data indicate that neonates are more vulnerable to severe
      infections due to immaturity of their immune system and emphasize the importance
      of vaccination in infants.

PMID- 18714022
TI  - Lipopolysaccharide is a direct agonist for platelet RNA splicing.
AB  - Platelets express TLR4 receptors, but its ligand LPS does not directly activate
      thrombotic functions nor, obviously, transcription by these anucleate cells.
      Platelets, however, store information that changes their phenotype over a few
      hours in the form of unprocessed RNA transcripts. We show even low concentrations
      of LPS in the presence of soluble CD14 initiated splicing of unprocessed IL-1beta
      RNA, with translation and accumulation of IL-1beta protein. LPS was a more robust
      agonist for this response than thrombin. Platelets also contained cyclooxygenase
      2 pre-mRNA, which also was spliced and translated after LPS stimulation. Flow
      cytometry and immunocytochemistry of platelets extensively purified by negative
      immunodepletion showed platelets contained IL-1beta, and quantitative assessment
      of white blood cell contamination by CD14 real time PCR confirms that leukocytes
      were not the IL-1beta source, nor were they required for platelet stimulation.
      LPS did not initiate rapid platelet responses, but over time did prime platelet
      aggregation to soluble agonists, induced actin rearrangement, and initiated
      granule secretion with P-selectin expression that resulted the coating of
      quiescent leukocytes with activated platelets. LPS is a direct agonist for
      platelets that allows these cells to directly participate in the innate immune
      response to bacteria.

PMID- 18714023
TI  - PKCbetaII augments NF-kappaB-dependent transcription at the CCL11 promoter via
      p300/CBP-associated factor recruitment and histone H4 acetylation.
AB  - The transcription factor NF-kappaB plays a pivotal role in regulating
      inflammatory gene expression. Its effects are optimized by various coactivators,
      including histone acetyltransferases (HATs) such as CREB-binding protein/p300 and
      p300/CBP-associated factor (p/CAF). The molecular mechanisms regulating cofactor
      recruitment are poorly understood. In this study, we describe a novel role for
      protein kinase C (PKC) betaIotaIota in augmenting NF-kappaB-mediated TNF-alpha
      induced transcription of the target gene CCL11 in human airway smooth muscle
      cells by phosphorylating the HAT p/CAF. Studies using reporters, overexpression
      strategies, kinase-dead and HAT-defective mutants, and chromatin
      immunoprecipitation showed that PKCbetaII activation was not involved in NF
      kappaB translocation, but facilitated NF-kappaB-mediated CCL11 transcription by
      colocalizing with and phosphorylating p/CAF, and thereby acetylating histone H4
      and promoting p65 association with the CCL11 promoter. The effect was dependent
      on p/CAF's HAT activity. Furthermore, mouse embryonic fibroblasts from PKCbeta
      knockout mice showed markedly reduced TNF-alpha-induced CCL11 expression and NF
      kappaB reporter activity that was restored on PKCbetaII overexpression,
      suggesting a critical role for this pathway. These data suggest a novel important
      biological role for PKCbetaIotaIota in NF-kappaB-mediated CCL11 transcription by
      p/CAF activation and histone H4 acetylation.

PMID- 18714024
TI  - Phosphorylation of 5-lipoxygenase at ser523 by protein kinase A determines
      whether pioglitazone and atorvastatin induce proinflammatory leukotriene B4 or
      anti-inflammatory 15-epi-lipoxin a4 production.
AB  - The 5-lipoxygenase (5LO) produces leukotriene B(4) and 15-epilipoxin-A(4) (15-epi
      LXA(4)). Phosphorylation at Ser(523) by protein kinase A (PKA) prevents 5LO shift
      to the perinuclear membrane. Atorvastatin and pioglitazone up-regulate 15-epi
      LXA(4) production in the heart. We assessed whether phosphorylation of 5LO by PKA
      determines whether 5LO interacts with the membranous cytosolic phospholipase A(2)
      (cPLA(2)) to produce leukotriene B(4) or with cyclooxygenase-2 (COX2) to produce
      15-epi-LXA(4). Rats received either pioglitazone, atorvastatin, pioglitazone plus
      atorvastatin, vehicle, or LPS. Rat myocardial cells were incubated with
      pioglitazone plus atorvastatin, pioglitazone plus atorvastatin plus H-89 (PKA
      inhibitor), H-89, or vehicle for 8 h. Pioglitazone and atorvastatin did not
      affect total 5LO expression. However, both increased 5LO levels in the cytosolic
      fraction. H-89 caused a shift of 5LO to the membranous fraction in atorvastatin-
      and pioglitazone-treated rats. Pioglitazone and atorvastatin increased phospho
      5LO levels. H-89 attenuated this increase. Both pioglitazone and atorvastatin
      increased COX2 levels in the cytosolic fraction and the membranous fraction. H-89
      prevented this increase. Pioglitazone and atorvastatin increased cPLA(2)
      expression in the membranous fraction. This effect was not attenuated by H-89.
      Pioglitazone plus atorvastatin increased 15-epi-LXA(4) levels. H-89 attenuated
      the effect of pioglitazone plus atorvastatin. Pioglitazone plus atorvastatin plus
      H-89 increased leukotriene B(4) levels. Coimmunoprecipitation showed that without
      H-89, atorvastatin and pioglitazone induced an interaction between 5LO and COX2
      in the cytosolic fraction, whereas when H-89 was added, 5LO interacted with
      cPLA(2) on the membranous fraction. The 5LO phosphorylation determines whether 15
      epi-LXA(4) (anti-inflammatory) or leukotriene B(4) (inflammatory mediator) is
      produced.

PMID- 18714025
TI  - Statins induce regulatory T cell recruitment via a CCL1 dependent pathway.
AB  - The statins, a group of inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A
      reductase, are reported to influence a variety of immune system activities
      through 3-hydroxy-3-methylglutaryl coenzyme A reductase-dependent and 
      independent mechanisms. How statin treatment regulates immune system function in
      vivo nonetheless remains to be fully defined. We analyzed the immunomodulatory
      effects of lovastatin in a Candida albicans-induced delayed-type hypersensitivity
      reaction in mice. In this model, lovastatin administration reduced the acute
      inflammatory response elicited by C. albicans challenge. This anti-inflammatory
      activity of lovastatin was associated with a shift from a Th1 to a Th2 immune
      response, as well as an increase in the percentage of regulatory T cells at the
      inflammation site and in the regional draining lymph node. The lovastatin-induced
      increase in regulatory T cells in the inflamed skin was dependent on expression
      of CCL1, a chemokine that is locally up-regulated by statin administration. The
      anti-inflammatory effect of lovastatin was abrogated in CCL1-deficient mice.
      These results suggest that local regulation of chemokine expression may be an
      important process in statin-induced modulation of the immune system.

PMID- 18714026
TI  - Splenectomy protects against sepsis lethality and reduces serum HMGB1 levels.
AB  - High mobility group box 1 (HMGB1) is a critical mediator of lethal sepsis.
      Previously, we showed that apoptotic cells can activate macrophages to release
      HMGB1. During sepsis, apoptosis occurs primarily in lymphoid organs, including
      the spleen and thymus. Currently, it is unclear whether this accelerated lymphoid
      organ apoptosis contributes to systemic release of HMGB1 in sepsis. In this
      study, we report that splenectomy significantly reduces systemic HMGB1 release
      and improves survival in mice with polymicrobial sepsis. Treatment with a broad
      spectrum caspase inhibitor reduces systemic lymphocyte apoptosis, suppresses
      circulating HMGB1 concentrations, and improves survival during polymicrobial
      sepsis, but fails to protect septic mice following splenectomy. These findings
      indicate that apoptosis in the spleen is essential to the pathogenesis of HMGB1
      mediated sepsis lethality.

PMID- 18714027
TI  - Mitochondrial structural changes and dysfunction are associated with experimental
      allergic asthma.
AB  - An imbalance between Th1 and Th2 immune response is crucial for the development
      of pathophysiological features of asthma. A Th2-dominant response produces
      oxidative stress in the airways, and it is thought to be one of the crucial
      components of asthma pathogenesis. Although mitochondrion is a crucial organelle
      to produce endogenous reactive oxygen species, its involvement in this process
      remains unexplored as yet. We demonstrate in this study that OVA-induced
      experimental allergic asthma in BALB/c mice is associated with mitochondrial
      dysfunction, such as reduction of cytochrome c oxidase activity in lung
      mitochondria, reduction in the expression of subunit III of cytochrome c oxidase
      in bronchial epithelium, appearance of cytochrome c in the lung cytosol,
      decreased lung ATP levels, reduction in the expression of 17 kDa of complex I in
      bronchial epithelium, and mitochondrial ultrastructural changes such as loss of
      cristae and swelling. However, there was no change in the expression of subunits
      II and III of cytochrome c oxidase. Interestingly, administration of IL-4 mAb
      reversed these mitochondrial dysfunction and structural changes. In contrast, IFN
      gamma mAb administration neither reversed nor further deteriorated the
      mitochondrial dysfunction and structural changes compared with control asthmatic
      mice administered with isotypic control Ab, although airway hyperresponsiveness
      deteriorated further. These results suggest that mitochondrial structural changes
      and dysfunction are associated with allergic asthma. These findings may help in
      the development of novel drug molecules targeting mitochondria for the treatment
      of asthma.

PMID- 18714028
TI  - The induction of inflammation by dectin-1 in vivo is dependent on myeloid cell
      programming and the progression of phagocytosis.
AB  - Dectin-1 is the archetypal signaling, non-Toll-like pattern recognition receptor
      that plays a protective role in immune defense to Candida albicans as the major
      leukocyte receptor for beta-glucans. Dectin-1-deficiency is associated with
      impaired recruitment of inflammatory leukocytes and inflammatory mediator
      production at the site of infection. In this study, we have used mice to define
      the mechanisms that regulate the dectin-1-mediated inflammatory responses.
      Myeloid cell activation by dectin-1 is controlled by inherent cellular
      programming, with distinct macrophage and dendritic cell populations responding
      differentially to the engagement of this receptor. The inflammatory response is
      further modulated by the progression of the phagocytosis, with "frustrated
      phagocytosis" resulting in dramatically augmented inflammatory responses. These
      studies demonstrate that dectin-1 in isolation is sufficient to drive a potent
      inflammatory response in a context-dependent manner. This has implications for
      the mechanism by which myeloid cells are activated during fungal infections and
      the processes involved in the therapeutic manipulation of the immune system via
      exogenous dectin-1 stimulation or blockade.

PMID- 18714029
TI  - Modulation of lipid and protein mediators of inflammation by cytosolic
      phospholipase A2alpha during experimental sepsis.
AB  - Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) is one of the key enzymes in
      lipid mediator generation. It preferentially hydrolyzes arachidonoyl-phospholipid
      in response to cellular stimuli, liberating arachidonic acid, the shared
      precursor of PGs and leukotrienes. Mice with disruption of the cPLA(2)alpha gene
      exhibit a more than 80% decrease in the generation of these lipid mediators,
      leading to dramatic phenotypes in various models of inflammatory and allergic
      disease. In this study, we use the cecal ligation and puncture model of sepsis
      along with multiplex quantitation systems to explore interactions between
      eicosanoids and protein mediators. cPLA(2)alpha-deficient mice exhibited
      significantly less weight loss accompanied by decreased generation of PGs,
      leukotriene B(4), IL-6, and CCL2. Despite these differences, genetic ablation of
      cPLA(2)alpha did not provide any survival advantage. Unexpectedly, abundant
      production of 12-hydroxy-eicosatetraenoic acid, another arachidonic acid-derived
      lipid mediator, was found to be unaffected by disruption of the cPLA(2)alpha
      gene. Eicosanoid production preceded the production of cytokines. Eicosanoid
      modulation of IL-6 and CCL2 expression was suggested by scattergram analyses.
      These results provide in vivo evidence for the rapid generation of eicosanoids,
      regulatory role(s) for cPLA(2)alpha-derived lipid mediators on protein mediator
      production, and the existence of a robust cPLA(2)alpha-independent pathway(s) of
      eicosanoid generation.

PMID- 18714030
TI  - Tissue-type plasminogen activator is a regulator of monocyte diapedesis through
      the brain endothelial barrier.
AB  - Inflammatory cell trafficking into the brain complicates several neurological
      disorders including multiple sclerosis. Normally, reliable brain functioning is
      maintained and controlled by the blood-brain barrier (BBB), which is essential to
      restrict the entry of potentially harmful molecules and cells from the blood into
      the brain. The BBB is a selective barrier formed by dedicated brain endothelial
      cells and dependent on the presence of intracellular tight junctions. In multiple
      sclerosis, a severe dysfunction of the BBB is observed, which is key to monocyte
      infiltration and inflammation in the brain. Proteolytic activity has been
      associated with these inflammatory processes in the brain. Our studies in plasma
      of rats indicated that the extracellular protease tissue-type plasminogen
      activator (tPA) correlates with the clinical signs of experimental allergic
      encephalomyelitis, a rat model of multiple sclerosis. In this study, we studied
      the function of the tPA during diapedesis of monocytes through a rat and human
      brain endothelial barrier. Monocyte-brain endothelial cell coculture experiments
      showed that monocytes induce the release of tPA by brain endothelial cells, which
      subsequently activates the signal transduction protein extracellular signal
      related kinase (ERK1/2), both involved in monocyte diapedesis. Importantly, live
      imaging and immunoblot analyses of rat brain endothelial cells revealed that tPA
      and ERK1/2 control the breakdown of the tight junction protein occludin. These
      studies identify tPA as a novel and relevant pathological mediator of
      neuroinflammation and provide a potential mechanism for this.

PMID- 18714032
TI  - Gp130 signaling promotes development of acute experimental colitis by
      facilitating early neutrophil/macrophage recruitment and activation.
AB  - IL-6 is known to play a crucial role in the pathogenesis of chronic intestinal
      inflammation by modulating T cell functions. In this study, we investigated the
      role of gp130, the common signal transducer for all IL-6 cytokines, in a murine
      model of acute T cell independent colitis to better characterize the impact of
      gp130 on innate immune cells and the early stages of inflammation. Experimental
      colitis was induced by dextran sulfate sodium treatment of mice with inducible
      systemic deletion of gp130 (MxCre/gp130(-/-)), macrophage/neutrophil-specific
      gp130-deficiency (LysCre/gp130(-/-)), or bone marrow chimeric mice and compared
      with wild-type controls (gp130(f/f)). Systemic deletion of gp130 (MxCre/gp130(-/
      )) protected mice from severe colitis and wasting and attenuated the mucosal
      inflammatory infiltrate as well as local cytokine, chemokine, and adhesion
      molecule expression. Experiments in newly generated macrophage/neutrophil
      specific gp130-deleted animals (LysCre/gp130(-/-)) and gp130 bone marrow chimeric
      mice, revealed a dual mechanism of proinflammatory effects mediated by gp130.
      Leukocyte recruitment was impaired in gp130-deleted animals and gp130-deleted
      recipients of wild-type bone marrow, demonstrating a central role of gp130
      dependent signals in nonmyeloid cells for directing leukocytes to sites of
      inflammation, which was further confirmed in a model of sterile peritonitis. In
      contrast, macrophage/neutrophil-specific gp130 deficiency delayed and attenuated
      the disease but only marginally affected the inflammatory infiltrate, indicating
      a defective activation of mucosal leukocytes. We provide evidence that IL-6
      cytokines acting via gp130 are required in the acute stages of intestinal
      inflammation by modulating the dynamics of innate immune cell recruitment and
      activation.

PMID- 18714031
TI  - Transcriptional and translational regulation of TGF-beta production in response
      to apoptotic cells.
AB  - Interaction between apoptotic cells and phagocytes through phosphatidylserine
      recognition structures results in the production of TGF-beta, which has been
      shown to play pivotal roles in the anti-inflammatory and anti-immunogenic
      responses to apoptotic cell clearance. Using 3T3-TbetaRII and RAWTbetaRII cells
      in which a truncated dominant-negative TGF-beta receptor II was stably
      transfected to avoid autofeedback induction of TGF-beta, we investigate the
      mechanisms by which TGF-beta was produced through PSRS engagement. We show, in
      the present study, that TGF-beta was regulated at both transcriptional and
      translational steps. P38 MAPK, ERK, and JNK were involved in TGF-beta
      transcription, whereas translation required activation of Rho GTPase, PI3K, Akt,
      and mammalian target of rapamycin with subsequent phosphorylation of translation
      initiation factor eukaryotic initiation factor 4E. Strikingly, these induction
      pathways for TGF-beta production were different from those initiated in the same
      cells responding to LPS or PMA.

PMID- 18714033
TI  - Myeloid-related proteins rapidly modulate macrophage nitric oxide production
      during innate immune response.
AB  - S100A8 and S100A9 are intracellular calcium-binding proteins produced by myeloid
      cells that promote neutrophil/monocyte recruitment at inflamed tissues by
      enhancing attachment to endothelial cells. Although the intracellular functions
      of these proteins, i.e., myeloid-related proteins (MRP)-8 and MRP-14, are not
      completely understood, these proteins exhibit prominent extracellular cytokine
      like functions and are considered reliable markers of inflammation in diverse
      diseases. As S100A8 and S100A9 have been reported to be rapidly released in
      response to components derived from infectious agents, we hypothesized that they
      play an important role in the modulation of key microbicidal phagocyte functions.
      In this study, we report for the first time that MRPs are powerful inducers of NO
      production by murine macrophages (Mphi). This increase in NO production was
      linked to an increased inducible NO synthase expression both at gene and protein
      level. This induction was concomitant with an important phosphorylation of
      SAPK/JNK, but also of MEK and ERK kinases. Upon stimulation with MRPs, NF-kappaB
      was rapidly translocated to the nucleus (30 min). When Mphi were treated
      concomitantly with IFN-gamma, another activator of Mphi functions, we observed a
      strong synergy in NO production, synergy that resulted from the engagement of
      exclusive signaling pathways: SAPK/JNK, ERK and NF-kappaB were involved in
      signaling of MRPs, whereas IFN-gamma uses the JAK/STAT pathway. This suggests
      that the synergy results from interactions of transcription factors in the
      promoter region. Finally, we observed this effect to be dependent on TLR4.
      Collectively, our study unravels the importance of MRPs as potent new inducers of
      Mphi NO production.

PMID- 18714034
TI  - Production of C5a by ASP, a serine protease released from Aeromonas sobria.
AB  - Aeromonas sobria causes pus and edema at sites of infection. However, the
      mechanisms underlying these effects have not been elucidated. C5a, the amino
      terminal fragment of the complement 5th component (C5), mimics these events. To
      investigate the involvement of C5a in the pathophysiology of A. sobria infection,
      we examined release of C5a from human C5 by a serine protease (ASP), a putative
      virulence factor secreted by this bacterium. C5 incubated with enzymatically
      active ASP induced neutrophil migration in a dose-dependent manner from an ASP
      concentration of 3 nM and in an incubation time-dependent manner in as little as
      7 min, with neutrophil accumulation in guinea pigs at intradermal injection sites
      and neutrophil superoxide release. These effects on neutrophils were inhibited by
      a C5a-receptor antagonist. The ASP incubation mixture with C5 but not C3 elicited
      vascular leakage in a dose- and incubation time-dependent manner, which was
      inhibited by a histamine H(1)-receptor antagonist. Together with these C5a-like
      activities, ASP cleaved C5 to release only one C5a Ag, the m.w. of which was
      similar to that of C5a. Immunoblotting using an anti-C5a Ab revealed generation
      of a C5a-like fragment from human plasma incubated with ASP. These results
      suggest that ASP-elicited neutrophil migration and vascular leakage via C5a
      production from C5 could occur in vivo, which was supported by that ASP did not
      affect functions of C5a and neutrophil C5a receptor. Through C5a generation, ASP
      could be associated with the induction of pus and edema caused by infection with
      this bacterium.

PMID- 18714036
TI  - Nucleotide oligomerization domains 1 and 2: regulation of expression and function
      in preadipocytes.
AB  - Translocation of bacteria into the mesenteric fat during intestinal inflammation
      and the expression of functional TLR1-9 in murine preadipocytes and adipocytes
      suggest an active role for these cells in innate immunity. The present study
      focuses on nucleotide oligomerization domains 1 and 2 representing intracellular
      pattern recognition receptors that sense motifs derived from bacterial
      peptidoglycans. On mRNA level nucleotide oligomerization domain 1 was found to be
      constitutively expressed in the preadipocyte cell line 3T3L1 and in primary
      preadipocytes isolated from murine mesenteric fat, while nucleotide
      oligomerization domain 2 was only weakly expressed by these cells. Treatment with
      lactyl-tetra-diaminopimelic acid, muramyl dipeptide, LPS, IL-1beta, and TNF-alpha
      did not affect cellular nucleotide oligomerization domain 1 mRNA amounts. Except
      muramyl dipeptide, all factors significantly increased nucleotide oligomerization
      domain 2 mRNA in mesenteric fat preadipocytes after 4 h. However, specific
      stimulation of nucleotide oligomerization domain 1 induced IL-6 synthesis in
      preadipocytes from wild-type or TLR2/4-deficient mice. Confirming nucleotide
      oligomerization domain 1 specificity, transfection of nucleotide oligomerization
      domain 1-specific small interfering RNA significantly blocked the effect of
      lactyl-tetra-diaminopimelic acid on IL-6 production. With specific inhibitors and
      a NF-kappaB reporter plasmid, nucleotide oligomerization domain 1-mediated
      activation of NF-kappaB was shown to be responsible for the induction of IL-6 in
      preadipocytes. In addition, expression of functional nucleotide oligomerization
      domain 1 could be confirmed in primary human preadipocytes. In summary, we here
      identified preadipocytes as a novel cell population expressing nucleotide
      oligomerization domains 1 and 2. Not regulated on transcriptional level,
      nucleotide oligomerization domain 1 in preadipocytes serves as a sensor for
      bacterial degradation products and triggers proinflammatory effector responses.
      Thus, our results further strengthen the allocation of the mesenteric fat and
      especially of preadipocytes to the innate immune system.

PMID- 18714035
TI  - Neutrophil apoptosis: selective regulation by different ligands of integrin
      alphaMbeta2.
AB  - Neutrophils undergo spontaneous apoptosis, but their survival can be extended
      during inflammatory responses. alpha(M)beta(2) is reported either to delay or
      accelerate neutrophil apoptosis, but the mechanisms by which this integrin can
      support such diametrically opposed responses are poorly understood. The abilities
      of closely related alpha(M)beta(2) ligands, plasminogen and angiostatin, derived
      from plasminogen, as well as fibrinogen and its two derivative alpha(M)beta(2)
      recognition peptides, P1 and P2-C, differed markedly in their effects on
      neutrophil apoptosis. Plasminogen, fibrinogen, and P2-C suppressed apoptosis via
      activation of Akt and ERK1/2 kinases, while angiostatin and P1 failed to activate
      these prosurvival pathways and did not prevent neutrophil apoptosis. Using cells
      transfected with alpha(M)beta(2) or its individual alpha(M) or beta(2) subunits,
      and purified receptors and its constituent chains, we show that engagement of
      both subunits with prosurvival ligands is essential for induction of the
      prosurvival response. Hence, engagement of a single integrin by closely related
      ligands can induce distinct signaling pathways, which can elicit distinct
      cellular responses.

PMID- 18714037
TI  - CD43 plays both antiadhesive and proadhesive roles in neutrophil rolling in a
      context-dependent manner.
AB  - As the first step in the recruitment of neutrophils into tissues, the cells
      become tethered to and roll on the vessel wall. These processes are mediated by
      interactions between the P- and E-selectins, expressed on the endothelial cells
      of the vessel wall, and their ligands, expressed on the neutrophils. Recently, we
      reported that CD43 on activated T cells functions as an E-selectin ligand and
      thereby mediates T cell migration to inflamed sites, in collaboration with P
      selectin glycoprotein ligand-1 (PSGL-1), a major P- and E-selectin ligand. Here,
      we examined whether CD43 on neutrophils also functions as an E-selectin ligand.
      CD43 was precipitated with an E-selectin-IgG chimera from mouse bone marrow
      neutrophils. A CD43 deficiency diminished the E-selectin-binding activity of
      neutrophils when PSGL-1 was also deficient. Intravital microscopy showed that the
      CD43 deficiency significantly increased leukocyte rolling velocities in TNF-alpha
      stimulated venules blocked with an anti-P-selectin mAb, where the rolling was
      mostly E-selectin dependent, when PSGL-1 was also absent. In contrast, in venules
      with trauma-induced inflammation, where the rolling was largely P-selectin
      dependent, the CD43 deficiency reduced leukocyte rolling velocities.
      Collectively, these observations suggest that CD43 generally serves as an
      antiadhesive molecule to attenuate neutrophil-endothelial interactions, but when
      E-selectin is expressed on endothelial cells, it also plays a proadhesive role as
      an E-selectin ligand.

PMID- 18714038
TI  - Characterization of HLA class II/peptide-TCR interactions of the immunodominant T
      cell epitope in Art v 1, the major mugwort pollen allergen.
AB  - More than 95% of mugwort pollen-allergic individuals are sensitized to Art v 1,
      the major allergen in mugwort pollen. Interestingly, the CD4 T cell response to
      Art v 1 involves only one single immunodominant peptide, Art v 1(25-36)
      (KCIEWEKAQHGA), and is highly associated with the expression of HLA-DR1.
      Therefore, we investigated the molecular basis of this unusual immunodominance
      among allergens. Using artificial APC expressing exclusively HLA-DRB1*0101 and
      HLA-DRA*0101, we formally showed that DR1 acts as restriction element for Art v
      1(25-36)-specific T cell responses. Further assessment of binding of Art v 1(25
      36) to artificial HLA-DR molecules revealed that its affinity was high for HLA
      DR1. Amino acid I27 was identified as anchor residue interacting with DR
      molecules in pocket P1. Additionally, Art v 1(25-36) bound with high affinity to
      HLA-DRB1*0301 and *0401, moderately to HLA-DRB1*1301 and HLA-DRB5*0101, and
      weakly to HLA-DRB1*1101 and *1501. T cell activation was also inducible by Art v
      1(25-36)-loaded, APC-expressing HLA molecules other than DR1, indicating
      degeneracy of peptide binding and promiscuity of TCR recognition. Specific
      binding of HLA-DRB1*0101 tetramers containing Art v 1(19-36) allowed the
      identification of Art v 1(25-36)-specific T cells by flow cytometry. In summary,
      the immunodominance of Art v 1(25-36) relies on its affinity to DR1, but is not
      dictated by it. Future investigations at the molecular HLA/peptide/TCR and
      cellular level using mugwort pollen allergy as a disease model may allow new
      insights into tolerance and pathomechanisms operative in type I allergy, which
      may instigate new, T cell-directed strategies in specific immunotherapy.

PMID- 18714040
TI  - Protection of murine systemic lupus by the Ea transgene without expression of I-E
      heterodimers.
AB  - A high-level expression of the Ea transgene encoding the MHC class II I-E alpha
      chain is very effective in the protection from systemic lupus erythematosus (SLE)
      in mice. However, it has not been elucidated whether this protection results from
      the induction or increased expression of I-E heterodimers or from the generation
      of I-E alpha-chain-derived peptides displaying high affinity for I-A molecules,
      because previous studies were conducted in lupus-prone mice expressing I-E beta
      chains. To address this question, we assessed the protective effect of the Ea
      transgene in lupus-prone BXSB mice bearing the H2(q) haplotype (i.e., unable to
      express I-E heterodimers because of a deficiency in I-E beta-chains). We observed
      that the Ea transgene expression resulted in a marked suppression of the
      development of SLE in H2(q) BXSB mice despite the absence of I-E expression. The
      observed protection was not associated with any detectable levels of T cell
      depletion and regulatory T cell expansion. Significantly, transgenic I-E alpha
      chains were substantially expressed on the surface of B lymphocytes and dendritic
      cells, but not of macrophages, without apparent formation of mixed-isotype
      heterodimers with I-A beta-chains. Our results demonstrate for the first time
      that the Ea transgene is able to prevent the development of SLE without induction
      of I-E heterodimer expression, indicating a critical role of I-E alpha-chains,
      but not I-E heterodimers, in the Ea transgene-mediated protection from SLE. Taken
      together, our data favor a model of autoimmunity prevention based on competition
      for Ag presentation between I-E alpha-chain-derived peptides and autoantigens.

PMID- 18714039
TI  - Potent simian immunodeficiency virus-specific cellular immune responses in the
      breast milk of simian immunodeficiency virus-infected, lactating rhesus monkeys.
AB  - Breast milk transmission of HIV is a leading cause of infant HIV/AIDS in the
      developing world. Remarkably, only a small minority of breastfeeding infants born
      to HIV-infected mothers contract HIV via breast milk exposure, raising the
      possibility that immune factors in the breast milk confer protection to the
      infants who remain uninfected. To model HIV-specific immunity in breast milk,
      lactation was pharmacologically induced in Mamu-A*01(+) female rhesus monkeys.
      The composition of lymphocyte subsets in hormone-induced lactation breast milk
      was found to be similar to that in natural lactation breast milk. Hormone-induced
      lactating monkeys were inoculated i.v. with SIVmac251 and CD8(+) T lymphocytes
      specific for two immunodominant SIV epitopes, Gag p11C and Tat TL8, and SIV viral
      load were monitored in peripheral blood and breast milk during acute infection.
      The breast milk viral load was 1-2 logs lower than plasma viral load through peak
      and set point of viremia. Surprisingly, whereas the kinetics of the SIV-specific
      cellular immunity in breast milk mirrored that of the blood, the peak magnitude
      of the SIV-specific CD8(+) T lymphocyte response in breast milk was more than
      twice as high as the cellular immune response in the blood. Furthermore, the
      appearance of the SIV-specific CD8(+) T lymphocyte response in breast milk was
      associated with a reduction in breast milk viral load, and this response remained
      higher than that in the blood after viral set point. This robust viral-specific
      cellular immune response in breast milk may contribute to control of breast milk
      virus replication.

PMID- 18714041
TI  - PP2A dephosphorylates Elf-1 and determines the expression of CD3zeta and FcRgamma
      in human systemic lupus erythematosus T cells.
AB  - T cells from patients with systemic lupus erythematosus are characterized by
      decreased expression of CD3zeta-chain and increased expression of FcRgamma-chain,
      which becomes part of the CD3 complex and contributes to aberrant signaling. Elf
      1 enhances the expression of CD3zeta, whereas it suppresses the expression of
      FcRgamma gene and lupus T cells have decreased amounts of DNA-binding 98 kDa form
      of Elf-1. We show that the aberrantly increased PP2A in lupus T cells
      dephosphorylates Elf-1 at Thr-231. Dephosphorylation results in limited
      expression and binding of the 98 kDa Elf-1 form to the CD3zeta and FcRgamma
      promoters. Suppression of the expression of the PP2A leads to increased
      expression of CD3zeta and decreased expression of FcRgamma genes and correction
      of the early signaling response. Therefore, PP2A serves as a central determinant
      of abnormal T cell function in human lupus and may represent an appropriate
      treatment target.

PMID- 18714042
TI  - IL-2 producing memory CD4+ T lymphocytes are closely associated with the
      generation of IgG-secreting plasma cells.
AB  - The role of specific CD4(+) T cell subsets in the induction of humoral immune
      responses in humans is largely unknown. In this study, the generation of
      hepatitis B surface Ag-specific CD4(+) T lymphocytes following vaccination was
      closely monitored and characterized at the single-cell level. The appearance and
      absolute numbers of hepatitis B surface Ag-specific IL-2 producing effector
      memory CD4(+) T lymphocytes was solely and tightly related to Ab titers reached.
      This relation remained present many years after vaccination. Subsequently, a
      relation was found between Ab titers and number of IL-2 producing memory CD4(+) T
      lymphocytes for various other Ags. These observations matched the findings of an
      in vitro assay, using different T cell subsets to induce B cell differentiation
      into IgG-producing plasma cells. By depleting for IL-2 producing memory T cells,
      we demonstrated that these cells are important for B cell differentiation into
      IgG-producing plasma cells. Finally, blocking the action of IL-2 with an IL-2R
      alpha Ab inhibited the differentiation of B lymphocytes into IgG-producing plasma
      cells. Based on these findings, we conclude that the development of Ag-specific
      IL-2-producing memory T cells appears to be essential for the development of IgG
      secreting plasma cells in humans.

PMID- 18714043
TI  - Chronic lymphocytic leukemia cells bind and present the erythrocyte protein band
      3: possible role as initiators of autoimmune hemolytic anemia.
AB  - The mechanisms underlying the frequent association between chronic lymphocytic
      leukemia (CLL) and autoimmune hemolytic anemia are currently unclear. The
      erythrocyte protein band 3 (B3) is one of the most frequently targeted Ags in
      autoimmune hemolytic anemia. In this study, we show that CLL cells specifically
      recognize B3 through a still unidentified receptor. B3 interaction with CLL cells
      involves the recognition of its N-terminal domain and leads to its
      internalization. Interestingly, when binding of erythrocyte-derived vesicles as
      found physiologically in blood was assessed, we observed that CLL cells could
      only interact with inside-out vesicles, being this interaction strongly dependent
      on the recognition of the N-terminal portion of B3. We then examined T cell
      responses to B3 using circulating CLL cells as APCs. Resting B3-pulsed CLL cells
      were unable to induce T cell proliferation. However, when deficient costimulation
      was overcome by CD40 engagement, B3-pulsed CLL cells were capable of activating
      CD4(+) T cells in a HLA-DR-dependent fashion. Therefore, our work shows that CLL
      cells can specifically bind, capture, and present B3 to T cells when in an
      activated state, an ability that could allow the neoplastic clone to trigger the
      autoaggressive process against erythrocytes.

PMID- 18714044
TI  - Memory B cells and pneumococcal antibody after splenectomy.
AB  - Splenectomized patients are susceptible to bloodstream infections with
      encapsulated bacteria, potentially due to loss of blood filtering but also
      defective production of anticarbohydrate Ab. Recent studies propose that a lack
      of Ab is related to reduced numbers of IgM(+) CD27(+) memory B cells found after
      splenectomy. To test this, we analyzed CD27(+) memory B cell subsets, IgG, and
      IgM pneumococcal Ab responses in 26 vaccinated splenectomized subjects in
      comparison to memory B cell subsets and Ab responses in healthy controls. As
      shown previously, the splenectomized autoimmune subjects had fewer total, isotype
      switched, and IgM(+) CD27(+) memory B cells as compared with controls, but there
      was no difference in memory B cells subsets between controls and splenectomized
      subjects with spherocytosis. There was no difference between the geometric mean
      IgG Ab response between normal controls and splenectomized subjects (p = 0.51; p
      = 0.81). Control subjects produced more IgM Ab than splenectomized autoimmune
      subjects (p = 0.01) but the same levels as subjects with spherocytosis (p =
      0.15.) There was no correlation between memory B cell subsets and IgG or IgM Ab
      responses for controls or splenectomized subjects. These data suggest that
      splenectomy alone may not be the sole reason for loss of memory B cells and
      reduced IgM antipneumococcal Ab. Because subjects with autoimmunity had
      splenectomy at a significantly older age than participants with spherocytosis,
      these data suggest that an age-related loss of extra splenic sites necessary for
      the maintenance or function of memory B cells may lead to impaired immunity in
      these subjects.

PMID- 18714045
TI  - Expression of a soluble TGF-beta receptor by tumor cells enhances dendritic
      cell/tumor fusion vaccine efficacy.
AB  - Dendritic cell (DC)-based antitumor immunotherapy is a promising cancer therapy.
      We have previously shown that tumor-derived TGF-beta limits the efficacy of the
      DC/tumor fusion vaccine in mice. In the current study we investigated the effect
      of neutralizing tumor-derived TGF-beta on the efficacy of the DC/tumor fusion
      vaccine. An adenovirus encoding human TGF-beta receptor type II fused to the Fc
      region of human IgM (Adv-TGF-beta-R) or a control adenovirus encoding LacZ (Adv
      LacZ) was used to express a soluble form of the neutralizing TGF-beta receptor
      (TGF-beta-R). Murine breast carcinoma cells, 4T1, but not bone marrow-derived
      DCs, were successfully transfected with Adv-TGF-beta-R (4T1+Adv-TGF-beta-R) using
      a multiplicity of infection of 300. Immunization with irradiated 4T1+Adv-TGF-beta
      R tumor cells conferred enhanced antitumor immunity compared with immunization
      with irradiated 4T1+Adv-LacZ tumor cells. The DC/4T1+Adv-TGF-beta-R fusion
      vaccine offered enhanced protective and therapeutic efficacy compared with the
      DC/4T1-Adv-LacZ fusion vaccine. Because TGF-beta is known to induce regulatory T
      cells (Tregs), we further showed that the DC/4T1+Adv-TGF-beta-R fusion vaccine
      induced fewer CD4(+)CD25(+)Foxp3(+) Tregs than the DC/4T1+Adv-LacZ fusion vaccine
      in vitro and in vivo. The suppressive role of splenic CD4(+)CD25(+) Tregs
      isolated from mice immunized with DC/4T1+Adv-LacZ was demonstrated using a CTL
      killing assay. Similar enhanced therapeutic efficacy was observed in murine renal
      cell carcinoma, RenCa, which expresses a high level of TGF-beta. We conclude that
      the blockade of tumor-derived TGF-beta reduces Treg induction by the DC/tumor
      fusion vaccine and enhances antitumor immunity. This may be an effective strategy
      to enhance human DC-based antitumor vaccines.

PMID- 18714048
TI  - Increased regulatory versus effector T cell development is associated with thymus
      atrophy in mouse models of multiple myeloma.
AB  - CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) play a central role in cancer
      tolerance. However, mechanisms leading to their accumulation in cancer remain
      unknown. Although the thymus is the main site of Treg development, thymic
      contribution to Treg expansion in cancer has not been directly examined. Herein,
      we used two murine models of multiple myeloma (MM), 5T2 MM and 5T33 MM, to
      examine Treg accumulation in peripheral lymphoid organs, including spleen, lymph
      nodes, bone marrow, and blood, and to explore thymic Treg development during
      malignancy. We found that peripheral ratios of suppressive-functional Tregs
      increased in both models of MM-inflicted mice. We found that thymic ratios of
      Treg development in MM increased, in strong association with thymus atrophy and
      altered developmental processes in the thymus. The CD4(+)CD8(+) double-positive
      population, normally the largest thymocyte subset, is significantly decreased,
      whereas the CD4(-)CD8(-) double-negative population is increased. Administration
      of thymocytes from MM-inflicted mice compared with control thymocytes resulted in
      increased progression of the disease, and this effect was shown to be mediated by
      Tregs in the thymus of MM-inflicted mice. Our data suggest that increased ratios
      of Treg development in the thymus may contribute to disease progression in MM
      inflicted mice.

PMID- 18714046
TI  - Inhalation of Staphylococcus aureus enterotoxin A induces IFN-gamma and CD8 T
      cell-dependent airway and interstitial lung pathology in mice.
AB  - Staphylococcus aureus, a primary source of bacterial superantigen (SAg), is known
      to colonize the human respiratory tract and has been implicated in airway
      inflammation. Studies have documented a role for SAgs in respiratory disorders,
      such as nasal polyps, chronic obstructive pulmonary disease, chronic
      rhinosinusitis, and asthma. However, cellular and molecular mediators involved in
      SAg-mediated pulmonary disease have not been clearly identified. In this study,
      we investigated the effect of intranasal staphylococcal enterotoxin A (SEA)
      exposure on murine lung. The pathological features in the lung resulting from SEA
      exposure had characteristics of both obstructive and restrictive pulmonary
      disorders. There was also an increase in bronchoalveolar lavage protein
      concentration and cellularity following SEA challenge. Massive CD8(+)Vbeta3(+) T
      cell accumulation observed in the lung was dependent on CD4 T cell help, both for
      recruitment and for IFN-gamma synthesis. The primary source of IFN-gamma
      synthesis was CD8 T cells, and depletion of these cells abrogated disease. IFN
      gamma deficiency also prevented SEA-mediated disease, and this was by enhancing
      early recruitment of neutrophils as detected in the bronchoalveolar lavage. Thus,
      IFN-gamma appeared to selectively aid the recruitment of T cells to the lungs
      while preventing the neutrophil accumulation. Therefore, our results show that
      IFN-gamma-producing CD8 T cells mediated pulmonary alveolitis and inflammation,
      which were dependent upon CD4 T cells for their recruitment to the lung.

PMID- 18714049
TI  - The cover. The madwoman.

PMID- 18714047
TI  - The Src kinase Lck facilitates assembly of HIV-1 at the plasma membrane.
AB  - HIV type 1 (HIV-1) assembly and egress are driven by the viral protein Gag and
      occur at the plasma membrane in T cells. Recent evidence indicates that secretory
      vesicles and machinery are essential components of virus packaging in both T
      cells and macrophages. However, the pathways and cellular mediators of Gag
      targeting to the plasma membrane are not well characterized. Lck, a lymphoid
      specific Src kinase critical for T cell activation, is found in the plasma
      membrane as well as various intracellular compartments and it has been suggested
      to influence HIV-1 replication. To investigate Lck as a potential regulator of
      Gag targeting, we assessed HIV-1 replication and Gag-induced virus-like particle
      release in the presence and absence of Lck. Release of HIV-1 and virus-like
      particles was reduced in the absence of Lck. This decrease in replication was not
      due to altered HIV-1 infection, transcription or protein translation. However, in
      T cells lacking Lck, HIV-1 accumulated intracellularly. In addition, expressing
      Lck in HeLa cells promoted HIV-1 Gag plasma membrane localization. Palmitoylation
      of the Lck unique domain, which is essential for directing Lck to the plasma
      membrane, was critical for its effect on HIV-1 replication. Furthermore, HIV-1
      Gag directly interacted with the Lck unique domain in the context of infected
      cells. These results indicate that Lck plays a key role in targeting HIV-1 Gag to
      the plasma membrane in T cells.

PMID- 18714050
TI  - A piece of my mind. About a boy.

PMID- 18714051
TI  - Microbiome project seeks to understand human body's microscopic residents.

PMID- 18714052
TI  - PTSD prevalence still high for persons living near World Trade Center attacks.

PMID- 18714053
TI  - Children of immigrants may face stresses, challenges that affect mental health.

PMID- 18714054
TI  - Pioglitazone vs glimepiride in the PERISCOPE trial.

PMID- 18714055
TI  - Pioglitazone vs glimepiride in the PERISCOPE trial.

PMID- 18714056
TI  - Insulin therapy and lipid overload in type 2 diabetes.

PMID- 18714057
TI  - Insulin therapy and lipid overload in type 2 diabetes.

PMID- 18714058
TI  - Usability of the Medicare health web site.

PMID- 18714059
TI  - Mortality and cardiovascular events in patients treated with homocysteine
      lowering B vitamins after coronary angiography: a randomized controlled trial.
AB  - CONTEXT: Observational studies have reported associations between circulating
      total homocysteine concentration and risk of cardiovascular disease. Oral
      administration of folic acid and vitamin B(12) can lower plasma total
      homocysteine levels. OBJECTIVE: To assess the effect of treatment with folic acid
      and vitamin B(12) and the effect of treatment with vitamin B(6) as secondary
      prevention in patients with coronary artery disease or aortic valve stenosis.
      DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind controlled trial
      conducted in the 2 university hospitals in western Norway in 1999-2006. A total
      of 3096 adult participants undergoing coronary angiography (20.5% female; mean
      age, 61.7 years) were randomized. At baseline, 59.3% had double- or triple-vessel
      disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary
      syndromes. INTERVENTIONS: Using a 2 x 2 factorial design, participants were
      randomly assigned to 1 of 4 groups receiving daily oral treatment with folic
      acid, 0.8 mg, plus vitamin B(12), 0.4 mg, plus vitamin B(6), 40 mg (n = 772);
      folic acid plus vitamin B(12) (n = 772); vitamin B(6) alone (n = 772); or placebo
      (n = 780). MAIN OUTCOME MEASURES: The primary end point was a composite of all
      cause death, nonfatal acute myocardial infarction, acute hospitalization for
      unstable angina pectoris, and nonfatal thromboembolic stroke. RESULTS: Mean
      plasma total homocysteine concentration was reduced by 30% after 1 year of
      treatment in the groups receiving folic acid and vitamin B(12). The trial was
      terminated early because of concern among participants due to preliminary results
      from a contemporaneous Norwegian trial suggesting adverse effects from the
      intervention. During a median 38 months of follow-up, the primary end point was
      experienced by a total of 422 participants (13.7%): 219 participants (14.2%)
      receiving folic acid/vitamin B(12) vs 203 (13.1%) not receiving such treatment
      (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P = .36) and 200
      participants (13.0%) receiving vitamin B(6) vs 222 (14.3%) not receiving vitamin
      B(6) (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P = .28).
      CONCLUSIONS: This trial did not find an effect of treatment with folic
      acid/vitamin B(12) or vitamin B(6) on total mortality or cardiovascular events.
      Our findings do not support the use of B vitamins as secondary prevention in
      patients with coronary artery disease. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00354081.

PMID- 18714061
TI  - Arsenic exposure and prevalence of type 2 diabetes in US adults.
AB  - CONTEXT: High chronic exposure to inorganic arsenic in drinking water has been
      related to diabetes development, but the effect of exposure to low to moderate
      levels of inorganic arsenic on diabetes risk is unknown. In contrast,
      arsenobetaine, an organic arsenic compound derived from seafood intake, is
      considered nontoxic. OBJECTIVE: To investigate the association of arsenic
      exposure, as measured in urine, with the prevalence of type 2 diabetes in a
      representative sample of US adults. DESIGN, SETTING, AND PARTICIPANTS: Cross
      sectional study in 788 adults aged 20 years or older who participated in the 2003
      2004 National Health and Nutrition Examination Survey (NHANES) and had urine
      arsenic determinations. MAIN OUTCOME MEASURE: Prevalence of type 2 diabetes
      across intake of arsenic. RESULTS: The median urine levels of total arsenic,
      dimethylarsinate, and arsenobetaine were 7.1, 3.0, and 0.9 mug/L, respectively.
      The prevalence of type 2 diabetes was 7.7%. After adjustment for diabetes risk
      factors and markers of seafood intake, participants with type 2 diabetes had a
      26% higher level of total arsenic (95% confidence interval [CI], 2.0%-56.0%) and
      a nonsignificant 10% higher level of dimethylarsinate (95% CI, -8.0% to 33.0%)
      than participants without type 2 diabetes, and levels of arsenobetaine were
      similar to those of participants without type 2 diabetes. After similar
      adjustment, the odds ratios for type 2 diabetes comparing participants at the
      80th vs the 20th percentiles were 3.58 for the level of total arsenic (95% CI,
      1.18-10.83), 1.57 for dimethylarsinate (95% CI, 0.89-2.76), and 0.69 for
      arsenobetaine (95% CI, 0.33-1.48). CONCLUSIONS: After adjustment for biomarkers
      of seafood intake, total urine arsenic was associated with increased prevalence
      of type 2 diabetes. This finding supports the hypothesis that low levels of
      exposure to inorganic arsenic in drinking water, a widespread exposure worldwide,
      may play a role in diabetes prevalence. Prospective studies in populations
      exposed to a range of inorganic arsenic levels are needed to establish whether
      this association is causal.

PMID- 18714060
TI  - Silver-coated endotracheal tubes and incidence of ventilator-associated
      pneumonia: the NASCENT randomized trial.
AB  - CONTEXT: Ventilator-associated pneumonia (VAP) causes substantial morbidity. A
      silver-coated endotracheal tube has been designed to reduce VAP incidence by
      preventing bacterial colonization and biofilm formation. OBJECTIVE: To determine
      whether a silver-coated endotracheal tube would reduce the incidence of
      microbiologically confirmed VAP. DESIGN, SETTING, AND PARTICIPANTS: Prospective,
      randomized, single-blind, controlled study conducted in 54 centers in North
      America. A total of 9417 adult patients (> or = 18 years) were screened between
      2002 and 2006. A total of 2003 patients expected to require mechanical
      ventilation for 24 hours or longer were randomized. INTERVENTION: Patients were
      assigned to undergo intubation with 1 of 2 high-volume, low-pressure endotracheal
      tubes, similar except for a silver coating on the experimental tube. MAIN OUTCOME
      MEASURES: Primary outcome was VAP incidence based on quantitative bronchoalveolar
      lavage fluid culture with 10(4) colony-forming units/mL or greater in patients
      intubated for 24 hours or longer. Other outcomes were VAP incidence in all
      intubated patients, time to VAP onset, length of intubation and duration of
      intensive care unit and hospital stay, mortality, and adverse events. RESULTS:
      Among patients intubated for 24 hours or longer, rates of microbiologically
      confirmed VAP were 4.8% (37/766 patients; 95% confidence interval [CI], 3.4%
      6.6%) in the group receiving the silver-coated tube and 7.5% (56/743; 95% CI,
      5.7%-9.7%) (P = .03) in the group receiving the uncoated tube (all intubated
      patients, 3.8% [37/968; 95% CI, 2.7%-5.2%] and 5.8% [56/964; 95% CI, 4.4%-7.5%]
      [P = .04]), with a relative risk reduction of 35.9% (95% CI, 3.6%-69.0%; all
      intubated patients, 34.2% [95% CI, 1.2%-67.9%]). The silver-coated endotracheal
      tube was associated with delayed occurrence of VAP (P = .005). No statistically
      significant between-group differences were observed in durations of intubation,
      intensive care unit stay, and hospital stay; mortality; and frequency and
      severity of adverse events. CONCLUSION: Patients receiving a silver-coated
      endotracheal tube had a statistically significant reduction in the incidence of
      VAP and delayed time to VAP occurrence compared with those receiving a similar,
      uncoated tube. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00148642.

PMID- 18714062
TI  - Within-person across-neuropsychological test variability and incident dementia.
AB  - CONTEXT: Neuropsychological tests are used to predict and diagnose dementia.
      However, to our knowledge, no studies to date have examined whether within-person
      across-neuropsychological test variability predicts dementia. OBJECTIVE: To
      examine whether within-person across-neuropsychological test variability predicts
      future dementia. DESIGN: The Einstein Aging Study (EAS) is a population-based
      longitudinal study of aging and dementia located in Bronx County, New York. We
      used Cox proportional hazards models using age as the time scale to estimate
      hazard ratios (HRs) for performance on individual neuropsychological tests (Free
      and Cued Selective Reminding Test, Digit Symbol Substitution subtest of the
      Wechsler Adult Intelligence Scale Revised, and the Vocabulary subtest of the
      Wechsler Adult Intelligence Scale Revised) and for within-person across
      neuropsychological test variability as predictors of incident dementia. Analyses
      were stratified by sex, and controlled for education and medical illness. SETTING
      AND PARTICIPANTS: A total of 1797 participants (age > or = 70 years) enrolled in
      the EAS between October 1993 and December 2007. Participants seen for the
      baseline visit only (n = 750), prevalent dementia cases (n = 72), and those with
      missing follow-up information (n = 78) were excluded. A total of 897 individuals
      were included in this investigation. Participants had follow-up visits every 12
      to 18 months. MAIN OUTCOME MEASURE: Incident dementia. RESULTS: Sixty-one cases
      of incident dementia were identified during follow-up (mean [SD], 3.3 [2.4]
      years), of which 26 were in the highest quartile of within-person across
      neuropsychological test variability. Adjusting for sex, education, and medical
      illness, variability was associated with incident dementia (HR for 1-point
      difference in variability, 3.93 [95% confidence interval {CI}, 2.04-7.56]). The
      association persisted even after adjusting for level of performance on individual
      neuropsychological tests (HR for 1-point difference in variability, 2.10 [95% CI,
      1.04-4.23]). Comparing Cox models using neuropsychological tests with and without
      within-person across-neuropsychological test variability showed that the former
      improved the prediction of dementia. Sensitivity in a model predicting dementia
      at 1 year also improved when neuropsychological test variability was included.
      CONCLUSIONS: In this population, within-person across-neuropsychological test
      variability was associated with development of incident dementia independent of
      neuropsychological test performance. This finding needs to be confirmed in future
      studies.

PMID- 18714063
TI  - A historical perspective of pharmaceutical promotion and physician education.

PMID- 18714064
TI  - The need to test the patient-centered medical home.

PMID- 18714065
TI  - Medicine, spirituality, and patient care.

PMID- 18714066
TI  - Polio today: are we on the verge of global eradication?

PMID- 18714067
TI  - Preventing ventilator-associated pneumonia: could silver-coated endotracheal
      tubes be the answer?

PMID- 18714068
TI  - Environmental arsenic exposure and diabetes.

PMID- 18714069
TI  - JAMA patient page. Ventilator-associated pneumonia.

PMID- 18714070
TI  - Dictyostelium discoideum--a promising expression system for the production of
      eukaryotic proteins.
AB  - In general, four different expression systems, namely, bacterial, yeast,
      baculovirus, and mammalian, are widely used for the overproduction of biochemical
      enzymes and therapeutic proteins. Clearly, bacterial expression systems offer
      ease of maneuverability with respect to large-scale production of recombinant
      proteins, while, a baculovirus expression system ensures proper protein
      modifications, processing, and refolding of complex proteins. Despite these
      advantages, mammalian cells remain the preferred host for many eukaryotic
      proteins of pharmaceutical importance, particularly, those requiring post
      translational modifications. Recently, the single-celled slime mold,
      Dictyostelium discoideum (Dd), has emerged as a promising eukaryotic host for the
      expression of a variety of heterologous recombinant eukaryotic proteins. This
      organism possesses the complex cellular machinery required for orchestrating post
      translational modifications similar to the one observed in higher eukaryotes.
      This review summarizes the advantages and disadvantages of Dictyostelium as an
      alternate system compared to other well-established expression systems. The key
      lessons learned from the expression of human recombinant proteins in this system
      are reviewed. Also, the strengths, weaknesses, and challenges associated with
      industrial-scale production of proteins in Dd expression system are discussed.

PMID- 18714071
TI  - [Various management strategies for problems encountered during menopause].

PMID- 18714073
TI  - Premature ovarian failure.

PMID- 18714074
TI  - Sleep and the menopause - do postmenopausal women experience worse sleep than
      premenopausal women?
AB  - OBJECTIVE: To examine the sleep characteristics in three cross-sectional
      populations: young, premenopausal and postmenopausal women, and the associations
      between sleep, menopause, mood and cognitive performance. STUDY DESIGN: Twenty
      one premenopausal (45-51 years), 29 postmenopausal (59-71 years) and 11 young (20
      26 years, using oral contraceptives) women were recruited. Polysomnography was
      used to measure objective sleep quality. Subjective sleep quality, sleepiness and
      mood were assessed using questionnaires. Cognitive performance was investigated
      by means of three attentional tests. RESULTS: Total sleep time in pre- and
      postmenopausal women was similar (404.9 and 384.7 minutes), but shorter than in
      young women (448.2 minutes, P = 0.030 and <0.003, respectively). Sleep efficiency
      followed the same pattern, being 84.3% in premenopausal (P = 0.027), 80.2% in
      postmenopausal (P < 0.003) and 93.4% in young women. Pre- and postmenopausal
      women had less slow wave sleep (duration or activity) and more wake time after
      sleep onset (duration or frequency). Insomnia complaints were more frequent after
      the menopause (P = 0.023). Sleepiness and mood scores were similar in all groups.
      Reaction speeds slowed with increasing age. After the menopause, better cognitive
      performance was associated with more rapid eye movement sleep. CONCLUSION:
      Objective sleep measures differed significantly between the young and
      postmenopausal groups. These differences may be more because of the physiology of
      ageing than the rapid changes across the menopause, since similar sleep
      characteristics were already present in the premenopausal women. The increase in
      sleep complaints after menopause was not associated with sleepiness or
      disturbances in objective sleep quality, mood or cognitive performance.

PMID- 18714075
TI  - Patient decision aid on natural health products for menopausal symptoms:
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate the impact of a patient decision aid (PDA) regarding the
      use of natural health products (NHPs) at menopause on decisional conflict,
      knowledge of NHPs, congruence between values and choice, persistence with an
      option, intention to disclose the use of NHPs to a physician or a pharmacist and
      intention to use decision support interventions in the future. STUDY DESIGN: A
      randomized controlled trial in which 90 women, aged 45-64 years, facing a
      decision about using NHPs for menopausal symptoms, received a PDA (experimental
      group) or a general information brochure about menopause (control group). Main
      outcome Decisional conflict. Measures Women were evaluated at baseline and after
      a two-week period using the decisional conflict scale (DCS). Analysis of
      covariance was used to determine the differences between both groups on the DCS.
      RESULTS: Both groups experienced a statistically significant reduction on the DCS
      (-0.55 +/- 0.59, P < 0.0001 versus -0.52 +/- 0.73, P < 0.0001). However, there
      was no statistically significant difference between the groups (P = 0.32). Both
      groups experienced a statistically significant improvement in knowledge of NHPs
      (0.86 +/- 1.77, P = 0.002 versus 0.51 +/- 1.47, P = 0.031). However, there was no
      statistically significant difference between the groups (P = 0.162). CONCLUSION:
      A PDA regarding the use of NHPs for menopausal symptoms impacted favourably on
      women's decisional conflict, but was not superior to a general information
      brochure on menopause.

PMID- 18714077
TI  - Testosterone and the breast.
AB  - Although women have been treated with testosterone (T) for female sexual
      dysfunction since the 1950s, the role of T in normal female physiology is not yet
      fully defined. One of the major safety concerns of androgen therapy is whether
      androgens have a stimulatory effect on the breast that could lead to breast
      carcinomas. The proposed mechanisms for such stimulation include local estrogen
      production from the aromatase enzyme complex present in the breast tissue or by
      the direct stimulation of the androgen receptor. Predominant data from in vitro
      studies have shown that androgens actually have apoptotic and antiproliferative
      effects and not stimulatory effects. Animal models have shown similar results to
      in vitro studies, finding that androgens inhibit breast cancer growth.
      Prospective and retrospective epidemiological analyses have shown mixed outcomes,
      with no clear consensus regarding androgen use and breast cancer risk.
      Hyperandrogenism in patients with polycystic ovarian syndrome with elevated
      levels of endogenous T is not associated with an increased risk of breast cancer
      and may, in fact, be protective. Another human model with excess of T is female
      to-male transgenderism, in which genotypic women are treated with large doses of
      exogenous T with no increased risk. High-dose androgen therapy also has been
      effective in treating patients with advanced breast cancer. Thus, the
      preponderance of data suggests that T use in females is not associated with an
      increased risk of breast carcinoma.

PMID- 18714078
TI  - Depression during menopausal transition: a review of treatment strategies and
      pathophysiological correlates.
AB  - It has long been recognized that women are at a higher risk than men to develop
      depression and that such risk is particularly associated with reproductive cycle
      events. Recent long-term, prospective studies have demonstrated that the
      transition to menopause is associated with higher risk for new onset and
      recurrent depression. A number of biological and environmental factors are
      independent predictors for depression in this population, including the presence
      of hot flushes, sleep disturbance, history of severe premenstrual syndrome or
      postpartum blues, ethnicity, history of stressful life events, past history of
      depression, body mass index, socioeconomic status and the use of hormones and
      antidepressants. Accumulated evidence suggests that ovarian hormones modulate
      serotonin and noradrenaline neurotransmission, a process that may be associated
      with underlying pathophysiological processes involved in the emergence of
      depressive symptoms during periods of hormonal fluctuation in biologically
      predisposed subpopulations. Transdermal estradiol and serotonergic and
      noradrenergic antidepressants are efficacious in the treatment of depression and
      vasomotor symptoms in symptomatic, midlife women. The identification of
      individuals whom might be at a higher risk for depression during menopausal
      transition could guide preventive strategies for this population.

PMID- 18714076
TI  - Prophylactic oophorectomy in premenopausal women and long-term health.
AB  - OBJECTIVE: To review the data on long-term outcomes in women who underwent
      prophylactic bilateral oophorectomy, a common surgical procedure that has more
      than doubled in frequency since the 1960s. STUDY DESIGN: Literature review of the
      published data on the consequences of prophylactic bilateral oophorectomy.
      Special emphasis was given to the Mayo Clinic Cohort Study of Oophorectomy and
      Aging. Main outcome measures Overall mortality, cardiovascular disease, cognitive
      impairment and dementia, parkinsonism, osteoporosis, psychological wellbeing and
      sexual function. RESULTS: There is a growing body of evidence suggesting that the
      premature loss of ovarian function caused by bilateral oophorectomy performed
      before natural menopause is associated with several negative outcomes. In
      particular, studies have revealed an increased risk of premature death,
      cardiovascular disease, cognitive impairment or dementia, parkinsonism,
      osteoporosis and bone fractures, decline in psychological wellbeing and decline
      in sexual function. The effects involve different organs (e.g. heart, bone, or
      brain), and different functions within organs (e.g. cognitive, motor, or
      emotional brain functions). Estrogen treatment may prevent some but not all of
      these negative outcomes. CONCLUSION: The potential adverse effects of
      prophylactic bilateral oophorectomy on heart health, neurological health, bone
      health and quality of life should be carefully weighed against its potential
      benefits for cancer risk reduction in women at average risk of ovarian cancer.

PMID- 18714079
TI  - Stress, health and ageing: a focus on postmenopausal women.
AB  - Stress influences health and disease and this might be of special relevance for
      ageing. The present review starts with the description of age-associated changes
      of the hypothalamic-pituitary-adrenal axis. In this context, the possible
      modulatory role of estradiol is discussed. Later, the influence of rising stress
      hormone levels for the ageing brain is illustrated and a few intervention
      strategies are outlined. At the end, the concept of allostatic load (AL) is
      described, which aims at a broader assessment of the impact of stress on the
      individual. The strengths and also the current limitations of the AL concept are
      highlighted.

PMID- 18714080
TI  - Sexually transmitted infections in the older woman.
AB  - Dependent upon sexual behaviour peri- and postmenopausal women are increasingly
      at risk of sexually transmitted infections, although the overall rates remain low
      when compared with younger people. Symptoms are often non-specific or absent and
      may be misinterpreted as being due to the menopause. In addition, both the women
      and their clinicians may not be aware of their infection risk, thus leading to a
      delayed or missed diagnosis. Risk assessment and referral for screening of
      infections should be carried out wherever appropriate.

PMID- 18714081
TI  - Urogenital atrophy.
AB  - The British Menopause Society Council aims to aid health professionals to inform
      and advise women about postreproductive health. This guidance refers to the long
      term condition of urogenital atrophy. Treatment choice should be based on up to
      date information and targeted to individual women's needs. Non-estrogen and
      estrogen-based treatments are discussed.

PMID- 18714082
TI  - Re: "genetic susceptibility to severe infection in families with invasive
      pneumococcal disease".

PMID- 18714083
TI  - Gamma frailty model for linkage analysis with application to interval-censored
      migraine data.
AB  - For many diseases, it seems that the age at onset is genetically influenced.
      Therefore, the age-at-onset data are often collected in order to map the disease
      gene(s). The ages are often (right) censored or truncated, and therefore, many
      standard techniques for linkage analysis cannot be used. In this paper, we
      present a correlated frailty model for censored survival data of siblings. The
      model is used for testing heritability for the age at onset and linkage between
      the loci and the gene(s) that influence(s) the survival time. The model is
      applied to interval-censored migraine twin data. Heritability (obtained from the
      frailties rather than actual onset times) was estimated as 0.42; this value was
      highly significant. The highest lod score, a score of 1.9, was found at the end
      of chromosome 19.

PMID- 18714084
TI  - Estimating the capacity for improvement in risk prediction with a marker.
AB  - Consider a set of baseline predictors X to predict a binary outcome D and let Y
      be a novel marker or predictor. This paper is concerned with evaluating the
      performance of the augmented risk model P(D = 1|Y,X) compared with the baseline
      model P(D = 1|X). The diagnostic likelihood ratio, DLR(X)(y), quantifies the
      change in risk obtained with knowledge of Y = y for a subject with baseline risk
      factors X. The notion is commonly used in clinical medicine to quantify the
      increment in risk prediction due to Y. It is contrasted here with the notion of
      covariate-adjusted effect of Y in the augmented risk model. We also propose
      methods for making inference about DLR(X)(y). Case-control study designs are
      accommodated. The methods provide a mechanism to investigate if the predictive
      information in Y varies with baseline covariates. In addition, we show that when
      combined with a baseline risk model and information about the population
      distribution of Y given X, covariate-specific predictiveness curves can be
      estimated. These curves are useful to an individual in deciding if ascertainment
      of Y is likely to be informative or not for him. We illustrate with data from 2
      studies: one is a study of the performance of hearing screening tests for
      infants, and the other concerns the value of serum creatinine in diagnosing renal
      artery stenosis.

PMID- 18714085
TI  - Dinucleotide-sensing proteins: linking signaling networks and regulating
      transcription.
AB  - Differential binding of dinucleotides to key regulatory proteins can modulate
      their interactions with other proteins and, in some cases, can signal
      fluctuations in the cellular redox state, to produce changes in transcription and
      physiological state. The dinucleotide-binding proteins human HSCARG and yeast
      transcription repressor Gal80p are examples that offer exciting glimpses into the
      potential for dinucleotide-sensing proteins to couple fluctuations in
      dinucleotide ratios to changes in transcription and to act as networking agents
      linking different classes of signaling molecules.

PMID- 18714086
TI  - Great times for small molecules: c-di-AMP, a second messenger candidate in
      Bacteria and Archaea.
AB  - Successful cell division in pro- and eukaryotes is ensured by checkpoints that
      regulate cell cycle progression. Structural and biochemical analyses of the DNA
      integrity scanning protein (DisA) have recently shown that its domain of unknown
      function, DUF147 [renamed DAC (for diadenylate cyclase)], has diadenylate cyclase
      activity. This diadenylate cyclase activity is abolished when DisA binds to
      branched DNA substrates, which arise during DNA double-strand breaks that can
      spontaneously occur during DNA replication. This finding identifies cyclic di(3'-
      >5')-adenylic acid (c-di-AMP) as a second messenger candidate that signals DNA
      integrity in Bacillus subtilis during sporulation, a specialized cell division
      process that leads to formation of a dormant cell called a spore. The DAC domain
      is widespread in Bacteria and Archaea; moreover, it is found in proteins
      containing diverse domains, suggesting that c-di-AMP acts as a second messenger
      molecule in response to various signals besides branched DNA. To elucidate the
      biological importance and molecular mechanisms of action for c-di-AMP and the
      recently recognized second messenger c-di-GMP will require a multidisciplinary
      approach.

PMID- 18714087
TI  - Characterization and kinetics study of off-gas emissions from stored wood
      pellets.
AB  - The full potential health impact from the emissions of biomass fuels, including
      wood pellets, during storage and transportation has not been documented in the
      open literature. The purpose of this study is to provide data on the
      concentration of CO(2), CO and CH(4) from wood pellets stored in sealed vessels
      and to develop a kinetic model for predicting the transient emission rate factors
      at different storage temperatures. Five 45-l metal containers (305 mm diameter by
      610 mm long) equipped with heating and temperature control devices were used to
      study the temperature effect on the off-gas emissions from wood pellets.
      Concurrently, ten 2-l aluminum canisters (100 mm diameter by 250 mm long) were
      used to study the off-gas emissions from different types of biomass materials.
      Concentrations of CO(2), CO and CH(4) were measured by a gas chromatograph as a
      function of storage time and storage temperature. The results showed that the
      concentrations of CO, CO(2) and CH(4) in the sealed space of the reactor
      increased over time, fast at the beginning but leveling off after a few days. A
      first-order reaction kinetics fitted the data well. The maximum concentration and
      the time it takes for the buildup of gas concentrations can be predicted using
      kinetic equations.

PMID- 18714088
TI  - A fast and accurate computational approach to protein ionization.
AB  - We report a very fast and accurate physics-based method to calculate pH-dependent
      electrostatic effects in protein molecules and to predict the pK values of
      individual sites of titration. In addition, a CHARMm-based algorithm is included
      to construct and refine the spatial coordinates of all hydrogen atoms at a given
      pH. The present method combines electrostatic energy calculations based on the
      Generalized Born approximation with an iterative mobile clustering approach to
      calculate the equilibria of proton binding to multiple titration sites in protein
      molecules. The use of the GBIM (Generalized Born with Implicit Membrane) CHARMm
      module makes it possible to model not only water-soluble proteins but membrane
      proteins as well. The method includes a novel algorithm for preliminary
      refinement of hydrogen coordinates. Another difference from existing approaches
      is that, instead of monopeptides, a set of relaxed pentapeptide structures are
      used as model compounds. Tests on a set of 24 proteins demonstrate the high
      accuracy of the method. On average, the RMSD between predicted and experimental
      pK values is close to 0.5 pK units on this data set, and the accuracy is achieved
      at very low computational cost. The pH-dependent assignment of hydrogen atoms
      also shows very good agreement with protonation states and hydrogen-bond network
      observed in neutron-diffraction structures. The method is implemented as a
      computational protocol in Accelrys Discovery Studio and provides a fast and easy
      way to study the effect of pH on many important mechanisms such as enzyme
      catalysis, ligand binding, protein-protein interactions, and protein stability.

PMID- 18714089
TI  - Atomic resolution structures of Escherichia coli and Bacillus anthracis malate
      synthase A: comparison with isoform G and implications for structure-based drug
      discovery.
AB  - Enzymes of the glyoxylate shunt are important for the virulence of pathogenic
      organisms such as Mycobacterium tuberculosis and Candida albicans. Two isoforms
      have been identified for malate synthase, the second enzyme in the pathway.
      Isoform A, found in fungi and plants, comprises approximately 530 residues,
      whereas isoform G, found only in bacteria, is larger by approximately 200
      residues. Crystal structures of malate synthase isoform G from Escherichia coli
      and Mycobacterium tuberculosis were previously determined at moderate resolution.
      Here we describe crystal structures of E. coli malate synthase A (MSA) in the apo
      form (1.04 A resolution) and in complex with acetyl-coenzyme A and a competitive
      inhibitor, possibly pyruvate or oxalate (1.40 A resolution). In addition, a
      crystal structure for Bacillus anthracis MSA at 1.70 A resolution is reported.
      The increase in size between isoforms A and G can be attributed primarily to an
      inserted alpha/beta domain that may have regulatory function. Upon binding of
      inhibitor or substrate, several active site loops in MSA undergo large
      conformational changes. However, in the substrate bound form, the active sites of
      isoforms A and G from E. coli are nearly identical. Considering that inhibitors
      bind with very similar affinities to both isoforms, MSA is as an excellent
      platform for high-resolution structural studies and drug discovery efforts.

PMID- 18714090
TI  - Copy number variation at the breakpoint region of isochromosome 17q.
AB  - Isochromosome 17q, or i(17q), is one of the most frequent nonrandom changes
      occurring in human neoplasia. Most of the i(17q) breakpoints cluster within a
      approximately 240-kb interval located in the Smith-Magenis syndrome common
      deletion region in 17p11.2. The breakpoint cluster region is characterized by a
      complex architecture with large ( approximately 38-49 kb), inverted and directly
      oriented, low-copy repeats (LCRs), known as REPA and REPB that apparently lead to
      genomic instability and facilitate somatic genetic rearrangements. Through the
      analysis of bacterial artificial chromosome (BAC) clones, pulsed-field gel
      electrophoresis (PFGE), and public array comparative genomic hybridization (array
      CGH) data, we show that the REPA/B structure is also susceptible to frequent
      meiotic rearrangements. It is a highly dynamic genomic region undergoing
      deletions, inversions, and duplications likely produced by non-allelic homologous
      recombination (NAHR) mediated by the highly identical SNORD3@, also known as U3,
      gene cluster present therein. We detected at least seven different REPA/B
      structures in samples from 29 individuals of which six represented potentially
      novel structures. Two polymorphic copy-number variation (CNV) variants, detected
      in 20% of samples, could be structurally described along with the likely
      underlying molecular mechanism for formation. Our data show the high
      susceptibility to rearrangements at the i(17q) breakpoint cluster region in the
      general population and exemplifies how large genomic regions laden with LCRs
      still represent a technical challenge for both determining specific structure and
      assaying population variation. The variant REPA/B structures identified may have
      different susceptibilities for inducing i(17q), thus potentially representing
      important risk alleles for tumor progression.

PMID- 18714094
TI  - Pharmacogenetics, therapeutic drug management offer new insights into treating
      pain.

PMID- 18714091
TI  - Mapping short DNA sequencing reads and calling variants using mapping quality
      scores.
AB  - New sequencing technologies promise a new era in the use of DNA sequence.
      However, some of these technologies produce very short reads, typically of a few
      tens of base pairs, and to use these reads effectively requires new algorithms
      and software. In particular, there is a major issue in efficiently aligning short
      reads to a reference genome and handling ambiguity or lack of accuracy in this
      alignment. Here we introduce the concept of mapping quality, a measure of the
      confidence that a read actually comes from the position it is aligned to by the
      mapping algorithm. We describe the software MAQ that can build assemblies by
      mapping shotgun short reads to a reference genome, using quality scores to derive
      genotype calls of the consensus sequence of a diploid genome, e.g., from a human
      sample. MAQ makes full use of mate-pair information and estimates the error
      probability of each read alignment. Error probabilities are also derived for the
      final genotype calls, using a Bayesian statistical model that incorporates the
      mapping qualities, error probabilities from the raw sequence quality scores,
      sampling of the two haplotypes, and an empirical model for correlated errors at a
      site. Both read mapping and genotype calling are evaluated on simulated data and
      real data. MAQ is accurate, efficient, versatile, and user-friendly. It is freely
      available at http://maq.sourceforge.net.

PMID- 18714096
TI  - Third accreditation option for hospitals may be available soon.

PMID- 18714097
TI  - FDA plans to continue cracking down on unapproved drugs.

PMID- 18714098
TI  - FDA program could boost treatments for neglected diseases.

PMID- 18714099
TI  - Instructing pharmacy students with interactive clinical cases.

PMID- 18714103
TI  - Celiac disease and osteoporosis.

PMID- 18714100
TI  - Important lessons in opioid selection.

PMID- 18714104
TI  - Implementation of insulin infusion guidelines in a neonatal intensive care unit.

PMID- 18714105
TI  - A tool kit for practice-based research.

PMID- 18714106
TI  - Eculizumab.
AB  - PURPOSE: The pharmacology, pharmacokinetics, indications, clinical efficacy,
      adverse effects, drug interactions, and dosage and administration of eculizumab
      are reviewed. SUMMARY: Eculizumab, a recombinant, humanized, monoclonal,
      immunoglobulin G antibody produced from murine myeloma cells, is the first agent
      to be approved for labeling by the Food and Drug Administration for the treatment
      of paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab works by inhibiting the
      complement cascade. It binds specifically to complement protein C5 and inhibits
      cleavage to C5a and C5b, resulting in the prevention of terminal complex
      formation and therefore cell lysis. In clinical studies, the effect of eculizumab
      on hemolysis was measured by a reduction in serum lactase dehydrogenase levels.
      The effect on hemolysis was evident after one week of treatment. The safety and
      efficacy of eculizumab were evaluated in a series of three trials. Results from
      the trials indicated that eculizumab reduces hemolysis and improves symptoms such
      as the number of paroxysms, dysphagia, and abdominal pain. The most frequent
      adverse reactions reported in the clinical trials included headache,
      nasopharyngitis, back pain, and nausea. The recommended i.v. dosing regimen is
      600 mg weekly for four weeks, followed by a 900-mg dose at week 5, and 900 mg
      every 14 days as a maintenance dose. The manufacturer recommends that patients
      who have not received meningococcal vaccine be vaccinated at least two weeks
      before starting therapy because eculizumab is associated with a high risk of
      meningococcal infection. CONCLUSION: Eculizumab represents a major advancement in
      the treatment of PNH. While clinical experience is limited, long-term studies in
      patients with PNH have supported the safe and effective use of eculizumab with
      few serious adverse effects.

PMID- 18714107
TI  - Factor VIIa (recombinant) for acute traumatic hemorrhage.
AB  - PURPOSE: The use of factor VIIa (recombinant) for the treatment of acute
      traumatic hemorrhage is reviewed. SUMMARY: Factor VIIa (recombinant) has received
      considerable attention as a hemostatic agent and is increasingly being used for
      the management of bleeding associated with a variety of conditions. Severely
      injured trauma patients with uncontrolled bleeding are at high risk for
      coagulopathy and may benefit from the administration of factor VIIa
      (recombinant). A literature review was conducted to identify original research in
      the form of randomized controlled trials investigating the use of factor VIIa
      (recombinant) for the treatment of traumatic hemorrhage. Due to the paucity of
      such trials, three retrospective evaluations and three large case series
      pertaining to this topic were also reviewed. Of the two randomized controlled
      trials, one found a reduction in red blood cell (RBC) transfusion requirements in
      patients with blunt traumatic hemorrhage after the administration of factor VIIa
      (recombinant). This reduction in RBC requirements was not found in the study
      conducted with patients with penetrating trauma. These trials were not powered to
      show a mortality difference, and the effect of factor VIIa (recombinant) on
      survival in blunt and penetrating traumatic hemorrhage is unknown. Ongoing
      clinical trials may answer questions regarding its effect on mortality and other
      clinically important outcomes. CONCLUSION: Factor VIIa (recombinant) reduces RBC
      transfusion requirements in patients with blunt traumatic hemorrhage, and its
      effect on mortality is currently being investigated. Adjunctive use of factor
      VIIa (recombinant) should be considered only after other treatment modalities
      have been optimized.

PMID- 18714108
TI  - Neuropsychiatric disturbance after initiation of varenicline in a patient with a
      history of alcohol abuse and major depression.
AB  - PURPOSE: The case of a patient with a history of alcohol abuse and major
      depression who developed neuropsychiatric symptoms after initiation of
      varenicline is reported. SUMMARY: A 33-year-old Caucasian man was prescribed
      varenicline for smoking cessation. He had a history of hypertension, alcohol
      dependency, major depression, and hypothyroidism. The patient's only reported
      allergy was to morphine. The patient reported smoking four or five cigarettes
      daily for 10 years and discontinued alcohol use 2 years before varenicline
      initiation. He was prescribed varenicline 0.5 mg once daily; after three days,
      the dosage was increased to 0.5 mg twice daily, based on recommendations in the
      package insert. On the evening of the seventh day, after taking 10 doses of
      varenicline, the patient developed severe anxiety, nausea, vertigo, blurred
      vision, and dizziness. He reported to his physician's office where his blood
      pressure was 120/75 mm Hg and his heart rate was approximately 70 beats/min. His
      laboratory test results were unremarkable for liver and kidney dysfunction. Since
      the only recent change to his drug therapy was the initiation of varenicline, the
      drug was discontinued, after which his symptoms subsided gradually and completely
      disappeared after three days. The patient declined rechallenge with varenicline
      one week later. The patient's score on the Naranjo et al. adverse drug reaction
      probability scale was 6, indicating a probable relationship between treatment
      with varenicline and the patient's symptoms. CONCLUSION: A patient with a history
      of alcohol dependence and major depression developed severe anxiety, nausea,
      vertigo, blurred vision, and dizziness after initiation of varenicline.

PMID- 18714109
TI  - Bupropion-induced angioedema.
AB  - PURPOSE: A case of angioedema caused by bupropion used for smoking cessation is
      discussed. SUMMARY: A 33-year-old man with a 12-pack-year of smoking history
      developed a rash on his extremities 18 days after the initiation of bupropion,
      followed by pruritus and swelling of the arms, feet, lower lip, and tongue by day
      20. Progression subsided after treatment with intravenous histamine antagonists
      and corticosteroids and required two emergency department visits. On day 22, the
      patient took his morning dose of bupropion as scheduled, which resulted in his
      symptoms returning. He discontinued bupropion on his own. The recommendation to
      discontinue the drug was not made or documented by the treating clinician. By day
      23, the diarrhea had subsided, the next day his swelling disappeared, and by day
      25, the pruritus had ceased. Cases of angioedema, a rare adverse effect of
      bupropion, have not been extensively described in previous literature. The
      reaction is linked to medications in 90% of all cases. Nonpitting edema typically
      affects the head and neck and may progress to respiratory failure. Failure to
      remove the causative agent may increase patient risk and result in increased
      health care costs, both of which occurred in this case. According to the Naranjo
      et al. probability scale, bupropion was deemed a definitive causative agent for
      this adverse reaction. CONCLUSION: A 33-year-old man developed angioedema during
      treatment with bupropion for smoking cessation.

PMID- 18714111
TI  - Pharmacist-led program to improve venous thromboembolism prophylaxis in a
      community hospital.
AB  - PURPOSE: The implementation of a pharmacist-led program to improve venous
      thromboembolism (VTE) prophylaxis is examined. SUMMARY: Nursing and pharmacy
      leaders at a 278-bed hospital reviewed VTE prophylaxis. The review revealed that
      among the total patient days for a month (excluding maternity, nursery,
      pediatric, and psychiatry patient days), prophylaxis was administered on only
      19.5% of those days. Pharmacy leadership viewed this as an opportunity to make
      hospitalwide improvements and offered to develop a pharmacist-led program to
      assess all new admissions for risk of VTE and to recommend appropriate
      pharmacologic prophylaxis. Under the new program, a pharmacist receives a daily
      report of all new admissions, which are cross-referenced with a report including
      patients currently prescribed heparin or low-molecular-weight heparin. Maternity,
      nursery, pediatric, and psychiatry patients are identified and excluded. The
      pharmacist assesses the remaining patients for VTE risk using a tracking sheet.
      The pharmacist then places all recommendations in the progress notes of the chart
      in the form of a bold sticker alerting the physician of known risk factors, VTE
      risk, and treatment recommendations. The program was developed to be performed
      seven days a week and maintained by one pharmacist per day for an average of four
      hours a day. Evaluation of the program three and six months after its
      implementation revealed marked increases in the use of prophylaxis and associated
      reductions in the occurrence of deep venous thrombosis (DVT) confirmed by Doppler
      ultrasonography. CONCLUSION: A pharmacist-led program for VTE prevention was
      associated with a significant increase in the prescribing of VTE prophylaxis and
      a significant reduction in ultrasonographically confirmed DVT.

PMID- 18714110
TI  - The Iowa Continuity of Care study: Background and methods.
AB  - PURPOSE: The background and methods of an ongoing study to determine the effects
      of hospital pharmacists' enhanced communication with patients and their community
      providers are described. SUMMARY: The Iowa Continuity of Care study is a
      randomized, prospective trial enrolling 1000 patients with selected medical
      conditions admitted to one large Midwest hospital. Patients will be randomized to
      a control group (usual care), minimal intervention, or enhanced intervention. For
      the intervention groups, a pharmacist case manager (PCM) will provide admission
      medication verification with the patients' community pharmacists, medication
      teaching, and discharge counseling. Patients in the enhanced intervention group
      will have a discharge care plan faxed to their outpatient physician and community
      pharmacist and will receive a follow-up phone call from the PCM three to five
      days after discharge; the PCM will continue to facilitate communication between
      the patient and community providers until all medication problems are resolved. A
      blinded research nurse will collect data, including adverse drug event (ADE)
      data, at admission and 30 and 90 days after discharge. The primary outcome
      measures include medication appropriateness, ADEs, emergency department visits,
      unscheduled office visits, and rehospitalizations. Data will be collected from
      the inpatient electronic medical record, outpatient physician medical records,
      and community pharmacist records and directly from patients. A cost-effectiveness
      analysis will be performed. CONCLUSION: This study will address the value of a
      PCM in improving communication of care plans between the inpatient and community
      settings and thereby optimizing medication use.

PMID- 18714112
TI  - Standardization of infusion solutions to reduce the risk of incompatibility.
AB  - PURPOSE: Although critically ill patients usually have various central
      intravenous (i.v.) lines, numerous drugs have to be infused simultaneously
      through the same lines. This can result in potentially harmful in-line
      incompatibility that can cause decreased drug effectiveness or increased
      microparticle load. To minimize the risk of these medication errors at an
      anesthesia intensive care unit (ICU), the preparation and administration of
      continuously infused drugs were standardized and the practicability in daily
      clinical routine was evaluated. SUMMARY: The concentration and diluent of
      continuously administered i.v. drugs were standardized. The drugs were grouped
      according to pH, medical indication, and chemical structure. The ICU staff
      decided to use multilumen central venous catheters, and each group of drugs was
      assigned to one lumen. Only drugs that belonged to the same group were infused
      simultaneously through the same lumen; therefore, intragroup incompatibilities
      had to be excluded before establishing the new drug administration plan at the
      ICU. The visual compatibility of 115 clinically reasonable intragroup drug
      mixtures was investigated. All drug combinations were compatible for six hours
      except mixtures containing thiopental, which was reassigned to a single-line use.
      In the following year, the practicability of this drug administration plan was
      evaluated. No deviations were found in the compliance of the staff prescribing
      and preparing only standardized concentrations and diluents. Further research to
      investigate the chemical compatibility of the drugs in these multiple mixtures
      will follow. CONCLUSION: A project intended to avoid incompatibility among i.v.
      drugs infused in the intensive care setting included steps to standardize
      solutions and determine which could be given together.

PMID- 18714113
TI  - Development and implementation of a telephone medication therapy management
      program for Medicare beneficiaries.
AB  - PURPOSE: A pharmacist-provided telephone medication therapy management (MTM)
      program for Medicare beneficiaries is discussed. SUMMARY: The Medicare
      Modernization Act of 2003 requires the provision of MTM to eligible
      beneficiaries. Using an MTM framework as a guide, Scott & White Health Plan
      (SWHP), a regional Medicare Part D plan, developed and implemented a pharmacist
      provided telephone MTM service for Medicare beneficiaries. A clinical pharmacist,
      practicing pharmacists, and physicians at SWHP were responsible for developing
      the MTM program. The MTM coordinator, who was also a pharmacist, worked with an
      information systems programmer to develop a custom-built database to support the
      documentation needs. Patients who were identified by SWHP as eligible to receive
      MTM services were mailed an MTM program information brochure each quarter. The
      brochure, which was sent out in two-week increments to manage the call volume,
      described the program and invited patients to participate. Interested patients
      were instructed to call SWHP to enroll in the MTM program. The medication therapy
      review, a core component of MTM, consisted of two steps: preassessment and
      assessment. Problems identified during the preassessment were confirmed or
      disproved, and during the assessment, medication-related problems were assessed.
      After the consultation, patients were mailed a portable personal medication
      record to use to fill out their medication lists. They also received a medication
      action plan that was tailored to each individual patient. The pharmacist provided
      consulting services and intervened to address medication- and health-related
      problems and to refer the patient to other health care providers if needed.
      CONCLUSION: A regional health plan successfully developed and implemented a
      telephone MTM service for Medicare beneficiaries provided and managed by
      pharmacists.

PMID- 18714114
TI  - Severity of medication administration errors detected by a bar-code medication
      administration system.
AB  - PURPOSE: The severity of medication administration errors detected by a bar-code
      medication administration (BCMA) system was studied. METHODS: A panel of six
      health care providers reviewed medication administration error scenarios created
      from BCMA error logs at six community hospitals. Each scenario was rated on the
      potential to cause patient harm, taking into account the severity of the
      potential outcome and the probability that the patient would be harmed. A
      severity score for each error was determined by averaging the individual
      reviewers' scores. RESULTS: The majority of the medication administration errors
      identified by the BCMA system were judged to be benign; 1% of the errors reviewed
      were rated as having the potential to result in a severe or life-threatening
      adverse event, 8% were judged to have the potential to produce moderate adverse
      effects, and 91% were expected to produce minimal, if any, clinical effects.
      Medication errors due to a dose being administered when there was no
      corresponding order in the computer system were significantly more likely to
      produce moderate or severe outcomes than other types of medication errors. Errors
      that involved medications designated as high-alert drugs were also more likely to
      produce moderate or severe adverse events than non-high-alert drugs. CONCLUSION:
      The majority of medication administration errors detected by a BCMA system were
      judged to be benign and pose minimal safety risks; however, the numbers and
      severity of medication administration errors that occur despite the use of a BCMA
      system suggest that there are opportunities to improve these systems and how the
      information they generate is used.

PMID- 18714115
TI  - Developing great research questions.
AB  - PURPOSE: The process for developing a good research question is described.
      SUMMARY: Three steps comprise the formulation of a great research question: (1)
      ask interesting questions, (2) select the best question for research, and (3)
      transform the research question into a testable hypothesis. Research is designed
      to generate information that cannot be gained from any other source. A research
      question is a narrow, challenging question addressing an issue, problem, or
      controversy that is answered with a conclusion based on the analysis and
      interpretation of evidence. A variety of strategies can be applied to stimulate
      creative thinking and generate new insights into old problems. A good research
      question challenges researchers to see matters from a new perspective and to
      learn something new. Practice research questions are evaluated by the probability
      of achieving their goal, along with the potential impact and feasibility of the
      project. The proposed research must meet important professional and societal
      goals, fit with the mission of the organization, garner administrative support,
      and be accomplished with available resources in a reasonable time frame. The
      research question should be refined to generate one or more hypotheses that
      specify the nature of the relationships to be observed and measured. Properly
      formulated questions yield findings to inform decisions that enhance practice,
      transfer to other settings, and make efficient use of resources. CONCLUSION:
      Developing a good research question is the most important part of the research
      process. The question should be narrow and address an important issue that fits
      within the mission of the organization.

PMID- 18714116
TI  - Longitudinal stability of sedentary behaviors and physical activity during early
      adolescence.
AB  - The purpose of this study was to examine the stability of sedentary behaviors and
      physical activity in Estonian school children aged 11-12 year at the beginning of
      the study. In addition, the consequence of changes in sedentary behaviors on a
      change in physical activity was investigated. Adolescents (N = 345) completed the
      3-Day Physical Activity Recall on four occasions over a 22-month period. Results
      indicated the curvilinear changes in sedentary behaviors and physical activity
      across time. There was a significant decrease in physical activity and an
      increase in sedentary behaviors across three years. Stability coefficients
      indicated a moderate differential stability of the sedentary behaviors (ranged
      from 0.31 to 0.64) and physical activity (ranged from 0.36 to 0.59) during early
      adolescence. Latent growth modeling indicated that increase in sedentary
      behaviors across a 22-month period was inversely associated with a change in
      physical activity. Interventions targeted at "high-risk" groups to reduce
      sedentary behaviors during early adolescence are encouraged.

PMID- 18714117
TI  - Asymmetry in volume between dominant and nondominant upper limbs in young tennis
      players.
AB  - This study aimed at demonstrating the asymmetry in volume between the dominant
      and nondominant upper limbs in tennis players, controlled for maturity status.
      Upper limb volumes on both sides were calculated in 72 tennis players and 84
      control subjects, using the truncated cone method. The participants' maturity
      status was determined using the predicted age at peak height velocity (PHV). The
      results showed significant larger side-to-side asymmetry in volume in tennis
      groups than in control groups. These findings suggested that, even before PHV,
      specific-sport adaptations occurred in the dominant upper limb in tennis players.

PMID- 18714118
TI  - Differences in physical activity levels between white and South Asian children in
      the United Kingdom.
AB  - The purpose of this study was to compare physical activity levels between white
      and South Asian children in the UK. The data were obtained from 606, 11-14 year
      old schoolchildren (397 white; 209 Asian). Physical activity was assessed using
      the 'four by one day' recall questionnaire from which the time spent in moderate
      and vigorous physical activity was calculated. Boys were significantly more
      active than girls (p = .0001), and white children reported significantly greater
      physical activity than south Asian children (p = .001). Mean +/- SD of time spent
      in moderate and vigorous activity was 90.2 +/- 65.4 mins and 68.2 +/- 49.3 mins
      for white and south Asian children and 103.5 +/- 63.4 mins and 65.6 +/- 53.5 mins
      for boys and girls respectively. These findings indicate that south Asian
      children are significantly less active than their white peers and there may be a
      need for specific interventions to target South Asian children particularly.

PMID- 18714119
TI  - Effect of relative changes in anthropometry during childhood on muscular power
      production in pedaling: a biomechanical simulation.
AB  - When performing skillful movement muscular and nonmuscular forces act in concert
      to produce a resultant force that complies with the goal of the task. Nonmuscular
      forces are directly dependent on the anthropometry of the performer. The purpose
      of this study was to determine the effect of age-related changes in relative
      anthropometric characteristics between 5 and 10 years of age on muscular power
      production during pedaling. A secondary purpose was to determine the dependence
      of this effect on movement speed. A torque-driven model of two-legged pedaling
      was used to track experimental kinematics and forces obtained from 6 experienced
      adult cyclists pedaling at 60 and 120 rpm. Relative anthropometric
      characteristics were modified to simulate pedaling for children of 5, 7.5, and 10
      years of age. Analyses of variance revealed that age-related differences in
      anthropometry did not affect the muscular contribution to crank power (p > .05),
      while they had a significant effect on the muscular contribution to limb power (p
      < .05). Adjustments by the proximal muscle groups (muscles spanning the hip and
      knee joints) were necessary to account for anthropometry-driven changes in
      nonmuscular power. These effects were independent of movement speed. Our results
      provide researchers with useful information to interpret age-related differences
      in muscular power production more accurately.

PMID- 18714120
TI  - An algorithm for identifying physical activity patterns from motion data.
AB  - An algorithm was developed to describe how physical activity (PA) patterns relate
      to overall motion counts. Thirty-five children wore an accelerometer (7-days).
      Each motion count was compared with the mean of surrounding counts within 21 min.
      Counts per minute similar to the mean were grouped into bouts. Counts that
      differed by more than 20% of the coefficient of variations (based on the mean and
      SD of the 21 min period) indicated transitions between bouts. Children with more
      daily motion had more and longer moderate (MPA) and vigorous (VPA) bouts, higher
      counts during MPA bouts, and more transitions from VPA to VPA bouts. In addition
      to differences in PA levels, highly active and less active children perform PA
      differently.

PMID- 18714121
TI  - Sociocultural correlates of physical activity in children and adolescents:
      findings from the Danish arm of the European Youth Heart study.
AB  - Cross-sectional associations between sociocultural factors and objectively
      measured physical activity in a sample of 397 children (aged 9) and 213
      adolescents (aged 15) were investigated. Associations with children's physical
      activity were found for mothers' physical activity (Beta = 80, p < .01), parental
      participation (Beta = 67, p = .01), mother's age (Beta=-8, p < .01) and, in
      girls, fathers' physical activity (Beta=73, p = .045; R2 for final model: 10.6%).
      No sociocultural factors were significantly associated with adolescents' physical
      activity. Parental factors might be important targets for interventions to
      increase children's physical activity but other factors may have greater
      influence. For adolescents' physical activity, factors from other domains may be
      more important to target.

PMID- 18714122
TI  - Use of session rating of perceived exertion for monitoring resistance exercise in
      children who are overweight or obese.
AB  - The purpose of this study was to investigate the use of the OMNI Resistance
      Exercise scale (OMNI-RES) for monitoring the intensity of different modes of
      resistance training in children who are overweight or obese. Sixty-one children
      (mean age = 9.7 +/- 1.4 years) performed three resistance training sessions every
      week for 4 weeks. Each session consisted of three sets of 3-15 repetitions of
      eight different resistance exercises. OMNI-RES RPE measures (0-10) were obtained
      following each set and following the end of the exercise session. There was a
      significant difference between average RPE (1.68 +/- 0.61) and Session RPE (3.10
      +/- 1.18) during the 4 weeks of training (p < .05). There was no significant
      change in session RPE over the 4 weeks of training. The correlation coefficient
      between average and session RPE values was significant (r = .88, p < .05). The
      findings of the current study indicate that the RPE values are higher when OMNI
      RES measures are obtained following the whole training session than when obtained
      following every single set of exercise. This suggests that in children the
      session RPE provides different information to the average RPE across the entire
      session.

PMID- 18714123
TI  - Predicting physical activity intention and behavior in school-age children.
AB  - Two studies were conducted to predict physical activity in school-aged children.
      Study 1 tested the utility of an integrated model in predicting physical activity
      (PA) intention and behavior-the theory of planned behavior (TPB) and self
      efficacy theory. Six hundred and forty-five New Zealand children (aged 11-13
      years) completed measures corresponding to the integrated model and a self
      reported measure of PA one week later. Perceived behavioral control (PBC) and
      subjective norm were the two strongest predictors of intentions. Task efficacy
      and barrier efficacy were the two strongest predictors of PA. A second study
      (Study 2) was conducted to determine whether the self-efficacy measures could
      discriminate objectively measured PA levels. Sixty-seven Canadian children (aged
      11-13 years) completed task and barrier self-efficacy measures. The following
      week, children classified as 'high' (n = 11) and 'lower' (n = 7) for both task
      and barrier efficacy wore an Actical(r) monitor for seven consecutive days to
      provide activity-related energy expenditure (AEE) data. Results showed that
      children with high efficacy expended significantly greater AEE than their lower
      efficacious counterparts. Findings from these two studies provide support for the
      use of self-efficacy interventions as a potentially useful means of increasing PA
      levels among school-aged children.

PMID- 18714124
TI  - The relationship between pedometer step counts and estimated VO2Max as determined
      by a submaximal fitness test in adolescents.
AB  - The purpose of this study was to examine the relationship between pedometer step
      counts and estimated VO2max as determined by a submaximal exercise test.
      Participants (N = 115; 65 girls, 50 boys) wore pedometers for five days and
      completed the Queen's College Step Test (QCST). Based on these results
      participants were classified as HIGH, MOD, or LOW cardiorespiratory fitness. Boys
      accumulated more steps per day (p < .05) than girls (12,766 +/- 4,923 versus
      10,887 +/- 2,656). The relationship between estimated VO2max and mean steps/day
      was moderate (r = .34, p < .01). Participants classified as having HIGH fitness
      levels accumulated more steps/day than LOW-fit adolescents (p < .05). The results
      from this study suggest that estimated VO2max as determined by a submaximal
      exercise test is moderately associated with mean steps/day in adolescents.

PMID- 18714125
TI  - 2008 FACE Poster Competition Abstracts. 9th Annual Fetal Alcohol Canadian
      Expertise (FACE) Research Roundtable. September 9, 2008 Montreal, Quebec.

PMID- 18714126
TI  - Selective extracellular stimulation of individual neurons in ganglia.
AB  - Selective control of individual neurons could clarify neural functions and aid
      disease treatments. To target specific neurons, it may be useful to focus on
      ganglionic neuron clusters, which are found in the peripheral nervous system in
      vertebrates. Because neuron cell bodies are found primarily near the surface of
      invertebrate ganglia, and often found near the surface of vertebrate ganglia, we
      developed a technique for controlling individual neurons extracellularly using
      the buccal ganglia of the marine mollusc Aplysia californica as a model system.
      We experimentally demonstrated that anodic currents can selectively activate an
      individual neuron and cathodic currents can selectively inhibit an individual
      neuron using this technique. To define spatial specificity, we studied the
      minimum currents required for stimulation, and to define temporal specificity, we
      controlled firing frequencies up to 45 Hz. To understand the mechanisms of
      spatial and temporal specificity, we created models using the NEURON software
      package. To broadly predict the spatial specificity of arbitrary neurons in any
      ganglion sharing similar geometry, we created a steady-state analytical model. A
      NEURON model based on cat spinal motor neurons showed responses to extracellular
      stimulation qualitatively similar to those of the Aplysia NEURON model,
      suggesting that this technique could be widely applicable to vertebrate and human
      peripheral ganglia having similar geometry.

PMID- 18714128
TI  - A cohort study of uranium millers and miners of Grants, New Mexico, 1979-2005.
AB  - A cohort mortality study of workers engaged in uranium milling and mining
      activities near Grants, New Mexico, during the period from 1955 to 1990 was
      conducted. Vital status was determined through 2005 and standardised mortality
      ratio (SMR) analyses were conducted for 2745 men and women alive after 1978 who
      were employed for at least six months. Overall, mortality from all causes (SMR
      1.15; 95% CI 1.07-1.23; n = 818) and all cancers (SMR 1.22; 95% CI 1.07-1.38; n =
      246) was greater than expected on the basis of US mortality rates. Increased
      mortality, however, was seen only among the 1735 underground uranium miners and
      was due to malignant (SMR 2.17; 95% CI 1.75-2.65; n = 95) and non-malignant (SMR
      1.64; 95% CI 1.23-2.13; n = 55) respiratory diseases, cirrhosis of the liver (SMR
      1.79; n = 18) and external causes (SMR 1.65; n = 58). The lung cancer excess
      likely is attributable to the historically high levels of radon in uranium mines
      of the Colorado Plateau, combined with the heavy use of tobacco products. No
      statistically significant elevation in any cause of death was seen among the 904
      non-miners employed at the Grants uranium mill. Among 718 mill workers with the
      greatest potential for exposure to uranium ore, no statistically significant
      increase in any cause of death of a priori interest was seen, i.e., cancers of
      the lung, kidney, liver, or bone, lymphoma, non-malignant respiratory disease,
      renal disease or liver disease. Although the population studied was relatively
      small, the follow-up was long (up to 50 yrs) and complete. In contrast to miners
      exposed to radon and radon decay products, for uranium mill workers exposed to
      uranium dusts and mill products there was no clear evidence of uranium-related
      disease.

PMID- 18714127
TI  - Spatio-temporal electrical stimuli shape behavior of an embodied cortical network
      in a goal-directed learning task.
AB  - We developed an adaptive training algorithm, whereby an in vitro neocortical
      network learned to modulate its dynamics and achieve pre-determined activity
      states within tens of minutes through the application of patterned training
      stimuli using a multi-electrode array. A priori knowledge of functional
      connectivity was not necessary. Instead, effective training sequences were
      continuously discovered and refined based on real-time feedback of performance.
      The short-term neural dynamics in response to training became engraved in the
      network, requiring progressively fewer training stimuli to achieve successful
      behavior in a movement task. After 2 h of training, plasticity remained
      significantly greater than the baseline for 80 min (p-value<0.01). Interestingly,
      a given sequence of effective training stimuli did not induce significant
      plasticity (p-value=0.82) or desired behavior, when replayed to the network and
      no longer contingent on feedback. Our results encourage an in vivo investigation
      of how targeted multi-site artificial stimulation of the brain, contingent on the
      activity of the body or even of the brain itself could treat neurological
      disorders by gradually shaping functional connectivity.

PMID- 18714129
TI  - A review of radon measurement studies in Pakistan.
AB  - Radon is being extensively measured all over the world due to its hazardous
      health effects as well as for different geological applications. In this regard,
      considerable studies have been conducted by different research groups in
      Pakistan. However, these studies are scattered and need to be combined/listed
      somewhere for future studies of radon in Pakistan. In this article, all the
      studies concerning radon measurements have been reviewed. The main emphasis is on
      different methods used in the measurement of radon. A minimum value of 5 Bq m(-3)
      has been reported for a centrally air conditioned room and a maximum value of 782
      +/- 125 Bq m(-3) has been observed in coal mines of Khushab, Punjab.

PMID- 18714130
TI  - Investigation of breast dose in five screening mammography centres in Greece.
AB  - The objectives of this study were to investigate the techniques currently used
      for screening mammography in Greece, to estimate the mean glandular dose (MGD)
      for establishing a baseline radiation dose database, to analyse the effects of
      various factors on MGD, and to compare the results with others in the literature.
      Five mammographic facilities and 250 women having as a routine screening
      mammogram one craniocaudal (CC) and one mediolateral oblique (MLO) projection in
      each breast were included in the study. The parameters recorded were age, weight,
      compressed breast thickness (CBT), tube potential (kV), tube loading (mA s) and
      MLO projection angle. Large differences were observed among the different
      mammography facilities, mainly in terms of the tube potential setting and the MLO
      angle used. The average MGD per exposure was 1.4 +/- 0.6 mGy while the respective
      averages separately for the CC and MLO projections were 1.2 +/- 0.5 and 1.5 +/-
      0.7 mGy, respectively. The average MGD values recorded in this study were below
      the limit of 2 mGy established for the reference medium-sized breast of 4.5 cm
      CBT. However, the variety of techniques observed revealed the need for a
      nationwide survey concerning screening mammography in Greece.

PMID- 18714131
TI  - Radioactivity concentrations and dose assessment for soil samples around nuclear
      power plant IV in Taiwan.
AB  - Activity concentrations and distributions of natural and man-made radionuclides
      in soil samples collected around nuclear power plant IV, Taiwan, were
      investigated for five years to assess the environmental radioactivity and
      characterisation of radiological hazard prior to commercial operation. The
      activity concentrations of radionuclides were determined via gamma-ray
      spectrometry using an HPGe detector. Data obtained show that the average
      concentrations of the (238)U and (232)Th series, and (40)K, were within world
      median ranges in the UNSCEAR report. The (137)Cs ranged from 2.46 +/- 0.55 to
      12.13 +/- 1.31 Bq kg(-1). The terrestrial absorbed dose rate estimated by soil
      activity and directly measured with a thermoluminescence dosemeter (excluding
      cosmic rays), and the annual effective doses, were 45.63, 57.34 nGy h(-1) and
      57.19 microSv, respectively. Experimental results were compared with
      international recommended values. Since the soil in this area is an important
      building material, the mean radium equivalent activity, external and inhalation
      hazard indices and the representative level index using various models given in
      the literature for the study area were 98.18 Bq kg(-1), 0.27, 0.34 and 0.73,
      respectively, which were below the recommended limits. Analytical results
      demonstrate that no radiological anomaly exists. The baseline data will prove
      useful and important in estimating the collective dose near the new nuclear power
      plant under construction in Taiwan.

PMID- 18714132
TI  - (226)Ra, (232)Th and (40)K contents in soil samples from Garhwal Himalaya, India,
      and its radiological implications.
AB  - The exposure of human beings to ionising radiation from natural sources is a
      continuing and inescapable feature of life on earth. Natural radionuclides are
      widely distributed in various geological formations and ecosystems such as rocks,
      soil groundwater and foodstuffs. In the present study, the distribution of
      (226)Ra, (232)Th and (40)K was measured in soil samples collected from different
      lithological units of the Thauldhar and Budhakedar regions of Garhwal Himalaya,
      India. The collected soil samples were analysed using gamma ray spectrometry. The
      activity concentrations of the naturally occurring radionuclides (226)Ra, (232)Th
      and (40)K in these soil samples were found to vary from below detection level
      (BDL) to 131 +/- 18 Bq kg(-1), 9 +/- 6 to 384 +/- 53 Bq kg(-1) and 471 +/- 96 to
      1406 +/- 175 Bq kg(-1), respectively. The distribution of radionuclides depends
      upon the rock formation and chemical properties within the earth. The activity
      concentrations vary widely depending on the sample origin. The external absorbed
      gamma dose rates due to (226)Ra, (232)Th and (40)K were found to vary from 49 to
      306 nGy h(-1). The average radium equivalent activity from these soil samples was
      300 Bq kg(-1).

PMID- 18714133
TI  - (226)Ra, (232)Th and (40)K contents and radon exhalation rate from materials used
      for construction and decoration in Cameroon.
AB  - This work deals with the measurement of radioactivity and radon exhalation rate
      from building materials manufactured in Douala city from geological materials.
      Nine types of building material were surveyed for their natural radioactivity
      contents using high-resolution gamma-ray spectrometry. The activity
      concentrations for (226)Ra, (232)Th and (40)K varied from 11.5 to 49 Bq kg(-1),
      16 to 37 Bq kg(-1) and 306 to 774 Bq kg(-1), respectively. The absorbed dose rate
      in the samples investigated at 1 m above ground level ranged from 28.5 to 66.6
      nGy h(-1). External and internal hazard indices were also estimated as defined by
      the European Commission. The Ra equivalents of the materials studied ranged from
      57.5 to 133 Bq kg(-1) and are much smaller than the recommended limit of 370 Bq
      kg(-1) for construction materials for dwellings. Polycarbonate nuclear track
      detectors (NTDs), type CR-39, were used for measuring the radon concentration
      from different materials. In fact, knowledge of the radon exhalation rate from
      building materials is important for understanding the individual contribution of
      each material to the total indoor radon exposure. Samples were hermetically
      closed in glass vessels and the radon growth was followed as a function of time.
      The radon exhalation rate was therefore derived from the experimental measurement
      of alpha-track densities. The radon exhalation varied from (5.77 +/- 0.06) x 10(
      5) to (7.61 +/- 0.07) x 10(-5) Bq cm(-2) h(-1) in bricks, from (5.79 +/- 0.05) x
      10(-5) to (11.6 +/- 0.12) x 10(-5) in tiles, and was (6.95 +/- 0.03) x 10(-5) Bq
      cm(-2) h(-1) in concrete. A correlation (correlation coefficient approximately
      0.8) was found between radium concentration measured with a HPGe detector and the
      radon exhalation rate obtained using nuclear track detectors.

PMID- 18714134
TI  - Soil radionuclide concentrations and radiological assessment in and around a
      refining and petrochemical company in Warri, Niger Delta, Nigeria.
AB  - Radioactivity measurements have been carried out using gamma-ray spectroscopy to
      determine the radionuclide concentrations in soil samples in the premises of the
      Warri Refining and Petrochemical Company located in the Niger Delta region of
      Nigeria and also in communities around it. The radionuclide contents of the crude
      oil and petroleum additives were also similarly determined. Results indicate that
      on the premises used by the company, the ranges of activity concentrations of
      (40)K, (226)Ra and (228)Th in the soil samples were 261.3-932.3 Bq kg(-1),<4.2
      23.0 Bq kg(-1) and<5.1-10.2 Bq kg(-1), respectively. For the 13 villages studied,
      activity concentrations ranged from <17.2-766.3 Bq kg(-1),<4.2-104.7 Bq kg(-1)
      and<5.1-13.7 Bq kg(-1), respectively, for (40)K, (226)Ra and (228)Th. The lowest
      radionuclide concentrations were found in the crude oil relative to the petroleum
      additives. The highest outdoor effective dose rate obtained in the study was 47.5
      microSv y(-1) for the villages and 35.2 microSv y(-1) within the company
      premises. These values are less than the world average outdoor value of 70
      microSv y(-1) given by UNSCEAR. Overall, it can be concluded that the long
      duration of refining activities does not seem to have affected radionuclide
      concentrations in the environment. Measurements also showed that the observed
      radiation dose rates did not vary significantly from the previously determined
      Warri City outdoor gamma radiation dose rates, for which the probability of
      occurrence of any health effects of radiation was judged low. The measurements,
      therefore, are interpreted to represent baseline radiometric data for future
      reference and research in the area.

PMID- 18714135
TI  - Syrian extensions to the Regulatory Authority Information System RAIS 3.0.
AB  - This paper describes the extensions which have been made in Syria to the
      Regulatory Authority Information System RAIS 3.0. These extensions cover a wide
      range of functionalities in the scope of RAIS 3.0 as well as in its interface.
      Compatibility with the original RAIS 3.0 has been maintained.

PMID- 18714136
TI  - Radionuclide contents in food products from domestic and imported sources in
      Nigeria.
AB  - Samples of some domestic and imported food products of nutritive importance to
      both the child population and the adult population in Nigeria were collected and
      analysed in order to determine their radionuclide contents. The samples were
      collected from open markets in major commercial cities in the country. Gamma-ray
      spectrometry was employed in the determination of the radionuclide contents in
      the products. The gamma-ray peaks observed with reliable regularity in all the
      samples analysed belong to naturally occurring radionuclides, namely (226)Ra,
      (228)Th and (40)K. The activity concentrations of these radionuclides in both the
      domestic and imported products were observed to be not significantly different.
      Essentially radioactive elements such as (137)Cs were not detected in any of the
      samples. The non-detection of (137)Cs in the imported products may be attributed
      to the suitably modified agricultural practices and countermeasures being
      employed to reduce caesium uptake by plants after the Chernobyl nuclear reactor
      accident. It seems unlikely that the elemental concentrations in the food
      products analysed will contribute significantly to public health risks in the
      country, as the cumulative ingestion effective dose values from (226)Ra and
      (228)Th were found to be low. Although (40)K has the highest activity
      concentrations in all the samples analysed, it is usually under homeostatic
      control in the body, and hence the concentrations are irrelevant to possible
      contamination in the food products analysed.

PMID- 18714137
TI  - Radiation information and informed consent for clinical trials.
AB  - Examples of the statements about the radiation from medical imaging in the
      information for participants provided to the Human Research Ethics Committee
      (HREC) for approval are presented and discussed. There is considerable scope for
      improvement in the information about radiation that is presented to potential
      participants in clinical trials. Many radiation statements seem only intended to
      allay fear and anxiety about radiation rather than providing accurate
      information. This situation cannot be said to be conducive to allowing the
      participant to give informed consent to their involvement in a clinical trial in
      which ionising radiation is used. As many clinical trials are international and
      conducted at many sites (sometimes over 100), we would expect the same statements
      to have been seen by members of HRECs in many countries. Few HRECs include a
      member who is an expert in radiation. Hence, to ensure that the information is
      sound, those sections of the participant information that refer to radiation
      should be written or reviewed by a specialist in radiation protection such as a
      medical physicist, a health physicist or a radiation safety officer.

PMID- 18714138
TI  - Childhood leukaemia incidence below the age of 5 years near French nuclear power
      plants.
AB  - A recent study indicated an excess risk of leukaemia among children under the age
      of 5 years living in the vicinity of nuclear power plants in Germany. We present
      results relating to the incidence of childhood leukaemia in the vicinity of
      nuclear power plants in France for the same age range. These results do not
      indicate an excess risk of leukaemia in young children living near French nuclear
      power plants.

PMID- 18714139
TI  - Radiological implications of granite of northern Pakistan.
AB  - Granite is an igneous rock that contains natural radioactivity of primordial
      radionuclides. In Pakistan, granite is distributed in a vast area called the
      Ambela Granitic Complex (AGC) in North West Frontier Province (NWFP). Granite is
      a hard rock that exists in different colours and is used to decorate floors,
      kitchen counter tops, etc. The use of granite in a building as a decor material
      is a potential source of radiation dose; therefore, natural radioactivity has
      been measured in 20 granite samples of the AGC with an HPGe (high purity
      germanium) based gamma ray spectrometer. The average specific activities and
      their range (given in parentheses) for primordial radionuclides (40)K, (226)Ra
      and (232)Th were 1218 (899-1927), 659 (46-6120) and 598 (92-3214) Bq kg(-1),
      respectively. The measured activity concentrations were used for the assessment
      of hazard indices and radiation dose which were evaluated based on the
      permissible limits defined for these parameters. The measured specific activities
      and the derived quantities, hazard indices and radiation dose, have been compared
      with those given in the literature for these parameters.

PMID- 18714140
TI  - A comparative study of lognormal, gamma and beta modelling in radon mapping with
      recommendations regarding bias, sample sizes and the treatment of outliers.
AB  - Radon risk maps have been produced in many countries using non-geologically based
      techniques utilising the lognormal and gamma distributions to display point
      estimates of the probability, P(RL), that indoor radon levels will exceed a
      reference level. Recent work on updating radon maps in Ireland prompted an
      examination of various statistical issues associated with non-geologically based
      radon mapping techniques. The purpose of this paper is to compare existing
      techniques with a new theoretically unbiased model which uses the beta
      distribution to estimate P(RL). We examine this new beta based model and four
      existing models for bias using simulated test data sets. Producing confidence
      intervals for P(RL), we also analyse the relationship between sample size and
      estimation error for each model and finally we consider the effect of extreme
      values on estimation procedures. We demonstrate that, under the assumption of
      lognormally distributed data with outliers, a two stage approach to testing which
      first detects and removes outliers from the data and then applies the beta based
      method is most satisfactory from both a theoretical and empirical perspective.

PMID- 18714141
TI  - The 1958 UNSCEAR report.
AB  - In the mid-1950s, concern was increasing about the possible effects from the
      radioactive fallout resulting from nuclear weapon testing. Various scientists
      from non-nuclear countries such as Sweden and Canada made their politicians aware
      of the potential hazards of fallout. This concern went up to the General Assembly
      of the United Nations, which took the unique step of appointing a scientific
      committee to advise it about the levels and effects of radiation, especially from
      nuclear bomb testing. The United Nations Scientific Committee on the Effects of
      Atomic Radiation was established in 1955 and held its first working meeting in
      September 1956. In less than two years it produced its first, pioneering report,
      which produced previously secret information about fallout exposure, and hitherto
      unknown information about natural background and medical exposure.

PMID- 18714143
TI  - Prevalence of disability among US- and foreign-born Arab Americans: results from
      the 2000 US Census.
AB  - BACKGROUND: Although the prevalence of disability for various racial and ethnic
      groups has been documented, little attention has been paid to Arab Americans in
      the United States. OBJECTIVES: We estimated the age- and sex-adjusted prevalence
      of disability among older Arab Americans and examined the association between
      nativity status and self-reported physical and self-care disability before and
      after controlling for covariates. METHODS: We used data from the 5% Public Use
      Microdata Samples of the 2000 US Census. Our sample included 4,225 individuals 65
      years of age and older who identified with an Arab ancestry. Of these, 2,280 were
      foreign-born and 1,945 were US-born. RESULTS: The age- and sex-adjusted
      prevalence of having a physical disability was 31.2% for foreign- and 23.4% for
      US-born older Arab Americans, and the age- and sex- adjusted prevalence of having
      a self-care disability was 13.5% for foreign- and 6.8% for US-born Arab
      Americans. Iraqis reported the highest estimates for both disabilities (physical,
      36.2%; self-care, 19.8%) compared to other Arab ethnic groups. In the crude
      model, foreign-born Arab Americans were more likely (OR=1.32; 95% CI=1.28, 1.36)
      to report a physical disability compared to US-born Arab Americans. When
      adjusting for English language ability in the final model, the odds of having a
      physical disability for foreign-born Arab Americans was protective compared to US
      born Arab Americans (OR=0.92; 95% CI=0.88, 0.96). In the crude model, foreign
      born Arab Americans were 1.82 times (95% CI=1.74, 1.90) more likely to report a
      self-care disability compared to US-born Arab Americans. In the fully adjusted
      model, this association was slightly attenuated (OR=1.32; 95% CI=1.24, 1.41).
      CONCLUSIONS: These findings indicate English language ability is associated with
      variations in reporting a physical disability. Future studies should include
      better measures of acculturation. Arab Americans are heterogeneous and should be
      disaggregated both by subgroups and from the white category in order to reveal a
      more accurate health and disease status profile for these groups. These efforts
      will assist in tailoring more effective interventions in reducing or preventing
      disability among Arab Americans 65 years of age and older.

PMID- 18714142
TI  - Human and mouse enamel phenotypes resulting from mutation or altered expression
      of AMEL, ENAM, MMP20 and KLK4.
AB  - Amelogenesis imperfecta (AI) is caused by AMEL, ENAM, MMP20 and KLK4 gene
      mutations. Mice lacking expression of the AmelX, Enam and Mmp20 genes have been
      generated. These mouse models provide tools for understanding enamel formation
      and AI pathogenesis. This study describes the AI phenotypes and relates them to
      their mouse model counterparts. Human AI phenotypes were determined in a clinical
      population of AI families and published cases. Human and murine teeth were
      evaluated using light and electron microscopy. A total of 463 individuals from 54
      families were evaluated and mutations in the AMEL, ENAM and KLK4 genes were
      identified. The majority of human mutations for genes coding enamel nonproteinase
      proteins (AMEL and ENAM) resulted in variable hypoplasia ranging from local
      pitting to a marked, generalized enamel thinning. Specific AMEL mutations were
      associated with abnormal mineralization and maturation defects. Amel and Enam
      null murine models displayed marked enamel hypoplasia and a complete loss of
      prism structure. Human mutations in genes coding for the enamel proteinases
      (MMP20 and KLK4) cause variable degrees of hypomineralization. The murine Mmp20
      null mouse exhibits both hypoplastic and hypomineralized defects. The currently
      available Amel and Enam mouse models for AI exhibit enamel phenotypes
      (hypoplastic) that are generally similar to those seen in humans. Mmp20 null mice
      have a greater degree of hypoplasia than humans with MMP20 mutations. Mice
      lacking expression of the currently known genes associated with the human AI
      conditions provide useful models for understanding the pathogenesis of these
      conditions.

PMID- 18714144
TI  - A 52-year-old male with fever and rapidly progressive dyspnea.

PMID- 18714145
TI  - Estradiol enables cortisol to act directly upon the pituitary to suppress
      pituitary responsiveness to GnRH in sheep.
AB  - We have shown that cortisol infusion reduced the luteinizing hormone (LH)
      response to fixed hourly GnRH injections in ovariectomized ewes treated with
      estradiol during the non-breeding season (pituitary-clamp model). In contrast,
      cortisol did not affect the response to 2 hourly invariant GnRH injections in
      hypothalamo-pituitary disconnected ovariectomized ewes during the breeding
      season. To understand the differing results in these animal models and to
      determine if cortisol can act directly at the pituitary to suppress
      responsiveness to GnRH, we investigated the importance of the frequency of GnRH
      stimulus, the presence of estradiol and stage of the circannual breeding season.
      In experiment 1, during the non-breeding season, ovariectomized ewes were treated
      with estradiol, and pulsatile LH secretion was restored with i.v. GnRH injections
      either hourly or 2 hourly in the presence or absence of exogenous cortisol.
      Experiments 2 and 3 were conducted in hypothalamo-pituitary disconnected
      ovariectomized ewes in which GnRH was injected i.v. every 2 h. Experiment 2 was
      conducted during the non-breeding season and saline or cortisol was infused for
      30 h in a cross-over design. Experiment 3 was conducted during the non-breeding
      and breeding seasons and saline or cortisol was infused for 30 h in the absence
      and presence of estradiol using a cross-over design. Samples were taken from all
      animals to measure plasma LH. LH pulse amplitude was reduced by cortisol in the
      pituitary clamp model with no difference between the hourly and 2-hourly GnRH
      pulse mode. In the absence of estradiol, there was no effect of cortisol on LH
      pulse amplitude in GnRH-replaced ovariectomized hypothalamo-pituitary
      disconnected ewes in either season. The LH pulse amplitude was reduced in both
      seasons in experiment 3 when cortisol was infused during estradiol treatment. We
      conclude that the ability of cortisol to reduce LH secretion does not depend upon
      the frequency of GnRH stimulus and that estradiol enables cortisol to act
      directly on the pituitary of ovariectomized hypothalamo-pituitary disconnected
      ewes to suppress the responsiveness to GnRH; this effect occurs in the breeding
      and non-breeding seasons.

PMID- 18714146
TI  - Computed tomography analysis of airway dimensions and lung density in patients
      with sarcoidosis.
AB  - BACKGROUND: It was previously reported that visual scores of the lung opacities
      were associated with lung function in patients with sarcoidosis. However, there
      are no reports on the evaluation of airway dimensions or lung density by computed
      tomography (CT) in sarcoidosis patients. OBJECTIVES: The aim of this study was to
      investigate whether airway dimensions and lung densities assessed by CT associate
      with pulmonary function in patients with sarcoidosis. METHODS: CT scanning was
      performed in 43 sarcoidosis patients and lung densities were measured using in
      house software. Means and standard deviations of lung density, kurtosis and
      skewness of lung density histograms were calculated. Tracheal area and airway
      wall area/total airway area (WA%) of the right apical bronchus were also
      measured. Pulmonary function tests were performed on the same day. RESULTS:
      Increased standard deviation of lung density and decreased kurtosis and skewness
      of lung density histograms were all associated with decreased total lung
      capacity, vital capacity and diffusion capacity. Increased standard deviation of
      lung density was also associated with decreased percentages of forced expiratory
      volume in 1 s and peak expiratory flow (%PEF). There was a positive correlation
      between tracheal area corrected by body surface area and %PEF, and negative
      correlation between WA% and %PEF. Stepwise regression analysis showed that
      increased standard deviation of lung density and decreased tracheal area were
      independently associated with lower %PEF. CONCLUSIONS: Thus, in sarcoidosis,
      densitometric parameters reflect restrictive lung function impairment. In
      addition to parenchymal lesions, it is concluded that the luminal area of the
      central airways also affects PEF.

PMID- 18714147
TI  - Food consumption analysis in spanish elderly based upon the mini nutritional
      assessment test.
AB  - BACKGROUND/AIMS: Aged people are an increasing population group worldwide, and
      nutritional impairments may contribute to additional health problems. The
      characterization of food consumption of elderly people is a good approach to
      implementing adequate nutritional policies in order to improve their nutritional
      status. The aim of this study was to describe and analyze specific aspects of
      food intake based upon the Mini Nutritional Assessment (MNA) test in a
      representative country sample. METHODS: The survey consisted of a cross-sectional
      study assessing the nutritional status of 22,007 Spanish people aged 65 years or
      older using the MNA test. These data, including dietary information, were
      obtained by health professionals specifically trained to carry out the
      questionnaire. A multiple regression analysis was used to evaluate the
      contributing impact of the diet-related MNA questions on the total MNA score.
      RESULTS: Differences in the food choices between men and women were found, but
      not in the mode of feeding. Obese and non-obese individuals, categorized by a
      body mass index (BMI) more or less than 30, showed similar intake patterns of
      protein-rich foods, but differences in fruits, vegetables and fluids. On the
      other hand, undernourished and non-undernourished subjects, according to the MNA
      criteria, revealed different food consumption. Loss of appetite and mode of
      feeding were the items with the highest influence the MNA total score.
      CONCLUSIONS: While age, gender and BMI considered together are responsible for
      11.3% of the total MNA score, dietary-related items can predict the 62.4% of the
      total MNA classification in the overall elderly Spanish population.

PMID- 18714148
TI  - Nutritional intake of children and adolescents with insulin-dependent diabetes
      mellitus in crete, Greece. A case-control study.
AB  - BACKGROUND/AIMS: The incidence of childhood insulin-dependent diabetes mellitus
      (IDDM) is rapidly increasing in Greece. The aim of this study was to examine
      nutrient patterns of children and adolescents with IDDM in Crete. METHODS: A case
      control survey of eating habits was conducted among 41 children and adolescents,
      aged 6-17 years, with IDDM (cases) and healthy sex- and age-matched controls,
      recruited from Heraklion University Hospital and the village of Rouvas, Crete,
      respectively. Dietary data was based on 24-hour recall records. RESULTS: Dietary
      intake was similar between the groups. Both groups exceeded the recommendations
      for total and saturated fat and consumed lower than recommended amounts of
      dietary fibre and total carbohydrates. Children with IDDM consumed more dairy
      products and vegetables and less meats and cereals. Vegetables were consumed by a
      relatively high proportion of children and adolescents in both groups, but there
      was a higher proportion of fruit consumers amongst the IDDM group. For those who
      ate fruit and vegetables, intake approximated current recommendations of 400
      g/day. CONCLUSIONS: The need to increase complex carbohydrates and reduce the
      consumption of total and saturated fat, in order to approach the traditional
      dietary pattern of Crete for this population, should be addressed via appropriate
      nutrition education programmes.

PMID- 18714149
TI  - Methylenetetrahydrofolate reductase 677CT polymorphism and cobalamin, folate, and
      homocysteine status in Spanish adolescents.
AB  - BACKGROUND: Folate and cobalamin are responsible for healthy growth. However, the
      B-vitamin and homocysteine status of adolescents is not well known. The aim was
      to assess the status of folate, cobalamin, and homocysteine in healthy Spanish
      adolescents. METHODS: Serum cobalamin, serum folate, homocysteine,
      methylenetetrahydrofolate reductase 677C>T variant, BMI, smoking habits, and
      Tanner stage were determined according to gender in 165 adolescents (84 females,
      81 males; 13-18.5 years) using the Student's t test, Mann-Whitney U test and
      chi(2) test, respectively. Interactions between socioeconomic status, age group,
      methylenetetrahydrofolate reductase polymorphism, BMI, smoking habits, Tanner
      stage, and vitamin status, respectively, were examined by ANOVA or Kruskal-Wallis
      H test (p < 0.05). RESULTS: Boys had markedly higher homocysteine (males 8.92
      (5.51-22.94) micromol/l; females 7.91 (5.09-13.86) micromol/l), whereas girls
      showed higher serum cobalamin concentrations (males 540.00 (268.00-946.47)
      pmol/l; females 594.82 (280.63-1,559.64) pmol/l). Data are shown as medians and
      the 2.5th to 97.5th percentiles in parentheses. Adolescents with the homozygous
      variant of methylenetetrahydrofolate reductase displayed significantly higher
      homocysteine and lower serum folate: normal 5.73 (3.09-10.73) ng/ml serum folate,
      7.57 (4.94-12.94) micromol/l homocysteine; homozygous 4.10 (2.75-7.88) ng/ml
      serum folate, 10.83 (7.00-22.82) micromol/l homocysteine. CONCLUSION: The present
      study provides data on the folate, cobalamin, and homocysteine status of Spanish
      adolescents. To assure a better assessment, revision of references for
      adolescents is still needed.

PMID- 18714150
TI  - A randomized double-blind, placebo-controlled study to establish the effects of
      spirulina in elderly Koreans.
AB  - AIMS: This study was conducted to determine the antioxidant capacity,
      immunomodulatory and lipid-lowering effects of spirulina in healthy elderly
      subjects and to document the effectiveness of spirulina as a functional food for
      the elderly. METHODS: A randomized double-blind, placebo-controlled study was
      performed. The subjects were 78 individuals aged 60-87 years and were randomly
      assigned in a blinded fashion to receive either spirulina or placebo. The elderly
      were instructed to consume the spirulina or placebo at home, 8 g/day, for 16
      consecutive weeks. RESULTS: In male subjects, a significant plasma cholesterol
      lowering effect was observed after the spirulina intervention (p < 0.05).
      Spirulina supplementation resulted in a significant rise in plasma interleukin
      (IL)-2 concentration, and a significant reduction in IL-6 concentration. A
      significant time-by-treatment intervention for total antioxidant status was
      observed between spirulina and placebo groups (p < 0.05). In female subjects,
      significant increases in IL-2 level and superoxide dismutase activity were
      observed (p < 0.05) after spirulina supplementation. There were significant
      reductions in total cholesterol in female subjects. CONCLUSIONS: The results
      demonstrate that spirulina has favorable effects on lipid profiles, immune
      variables, and antioxidant capacity in healthy, elderly male and female subjects
      and is suitable as a functional food.

PMID- 18714151
TI  - Effect of smoking habit on circulating adipokines in diabetic and non-diabetic
      subjects.
AB  - BACKGROUND: Despite the well-known inverse association between smoking and body
      weight, there have been conflicting reports on the association between smoking
      and adipokines such as leptin and adiponectin. AIM: To determine and compare
      whether tobacco smoking (cigarettes or sheesha) affects circulating levels of
      adiponectin and/or influences leptin and leptin receptor (sOb-R) concentrations
      and free leptin in diabetic and non-diabetic subjects. METHODS AND SUBJECTS:
      Fasting plasma adiponectin, leptin, sOb-R, glucose, insulin, and lipid profile
      were determined in 236 subjects grouped as control subjects (n = 53); non
      diabetic cigarette smokers (n = 34), non-diabetic sheesha smokers (n = 38),
      diabetic nonsmokers (n = 75) and diabetic smokers (n = 36). Uni- and multivariate
      regression analyses were used to determine the associations of these variables
      with body mass index (BMI) and smoking. RESULTS: When compared to control
      subjects, smoking cigarettes or sheesha was associated with significantly higher
      glucose, insulin resistance, total cholesterol, triglycerides, low-density
      lipoprotein cholesterol (LDL-C) and lower serum leptin, sOb-R and free leptin.
      The effects of smoking on BMI, leptin and sOb-R were dose-dependent. Binary
      logistic regression analysis showed that smoking is a significant determinant of
      BMI; leptin, sOb-R, free leptin index, adiponectin and LDL-C. CONCLUSIONS: We
      conclude that smoking sheesha does not reduce the metabolic effects of smoking.
      Smoking may modify leptin receptors and modulate leptin synthesis but the weight
      lowering effect may not be related to leptin-induced anorectic signals.

PMID- 18714152
TI  - Effect of oral L-carnitine administration on insulin sensitivity and lipid
      profile in type 2 diabetes mellitus patients.
AB  - AIM: It was the aim of this study to evaluate the effect of oral L-carnitine
      administration on insulin sensitivity and lipid profile in subjects with type 2
      diabetes mellitus. SUBJECTS AND METHODS: A randomized, double-blind, placebo
      controlled clinical trial was carried out in 12 subjects with type 2 diabetes.
      Six subjects received L-carnitine 1 g orally 3 times a day before meals for a
      period of 4 weeks. Six other individuals took a placebo for the same period of
      time, as the control group. Before and after the intervention, insulin
      sensitivity and the lipid profile were estimated. To assess insulin sensitivity,
      the euglycemic-hyperinsulinemic clamp technique was performed. Wilcoxon's signed
      rank and the Mann-Whitney U test were used for the statistical analyses. RESULTS:
      There were no significant differences in basal clinical characteristics between
      the 2 groups. Insulin sensitivity and the basal lipid profile were similar. There
      were no significant changes in either group after the intervention in insulin
      sensitivity (3.2 +/- 1.2 vs. 4.5 +/- 1.7 mg/kg/min, p = 0.115, and 3.5 +/- 0.6
      vs. 3.5 +/- 0.4 mg/kg/min, p = 0.917, for the placebo and L-carnitine groups,
      respectively) and in lipid profile. CONCLUSION: L-Carnitine orally administered
      for a period of 4 weeks did not modify insulin sensitivity or the lipid profile.

PMID- 18714153
TI  - High-dose chemotherapy without stem cell transplantation for refractory childhood
      systemic lupus erythematosus.
AB  - BACKGROUND: Intensive chemotherapy followed by autologous hematopoietic stem cell
      transplantation (ASCT) is effective for refractory systemic lupus erythematosus
      (SLE). When intensive chemotherapy is immunoablative but nonmyeloablative, ASCT
      for hematopoietic reconstitution, with the risk of reinfusing autoreactive
      lymphocytes, is unnecessary. METHODS: Four children aged 12-16 years were
      enrolled, 3 with WHO class IV nephritis, 2 with hemolytic anemia and 1 with
      thrombocytopenia. Median disease duration prior to the study was 4 years (range 1
      6). Previous therapy, including intravenous bolus cyclophosphamide (Cy) with a
      median accumulated dose of 6.5 g/m(2) and high-dose methylprednisolone with a
      median accumulated dose of 370 mg/kg, had failed. The protocol included: Cy 1.2
      g/m(2) daily for 4 days, fludarabine 30 mg/m(2) daily for 4 days, porcine
      antilymphocyte globulin 25 mg/kg daily for 3 days. RESULTS: Themedian duration of
      absolute neutrophil count <0.5 x 10(9)/l was 5.5 days after treatment. The median
      SLE Disease Activity Index and urine protein decreased from 8.5 and 3.4 to 1.0
      and 0.1 g/day at the date of last follow-up (median 20 months), respectively. Two
      cases with hemolytic anemia and 1 with thrombocytopenia before treatment
      recovered to normal or near normal hemogram, respectively. All patients achieved
      complete or partial remission within 10-28 months of follow-up. CONCLUSION:
      Intensive chemotherapy leads to rapid hematopoietic reconstitution without ASCT
      and appears beneficial in refractory childhood SLE. Further study is needed.

PMID- 18714154
TI  - Vincristine-induced neuropathy in the rat is not modified by drug-drug
      interactions with the P-glycoprotein inhibitor verapamil.
AB  - BACKGROUND: Cancer patients can be exposed to drug interactions during treatment
      with toxic anticancer drugs. The peripheral nervous system is a target for
      neurotoxic anticancer drugs. P-glycoprotein is essential for the functional
      integrity of blood-tissue barriers, and P-glycoprotein inhibition due to possible
      drug interactions could lead to adverse neurotoxic reactions. METHODS: In a rat
      model of vincristine-induced neuropathy, we assessed the consequences of
      potential drug interactions of vincristine with some P-glycoprotein-inhibiting
      drugs, chosen because of their potency to increase the incorporation of (99m)Tc
      sestamibi in nervous tissue. RESULTS: Quinidine (30 mg/kg) increased (99m)Tc
      sestamibi incorporation in dorsal root ganglia (DRG) but was toxic for rats.
      Verapamil (30 mg/kg) increased the tracer incorporation in the spinal cord, DRG
      and sciatic nerve. Combination treatment with the verapamil-vincristine regimen
      had a tendency to lower weight gain and altered nociceptive thresholds of
      neuropathic animals. CONCLUSION: Behavioral pain tests did not reveal an increase
      in vincristine neurotoxicity following combination treatment with verapamil and
      vincristine. This regimen only led to a slight increase in general toxicity.

PMID- 18714155
TI  - Characterization of 5-fluorouracil-resistant cholangiocarcinoma cell lines.
AB  - BACKGROUND: Although 5-fluorouracil (5-FU) is the drug of choice for the
      palliative treatment of cholangiocarcinoma (CCA), resistance to the drug is a
      therapeutic obstacle. The aim of this study was to explore the mechanisms
      underlying 5-FU resistance of CCA using cell lines derived from CCA associated
      with liver fluke infection. METHODS: A stepwise exposure was used for inducing 5
      FU-resistant CCA cell lines, and the expression of nine genes associated with 5
      FU resistance was analyzed using real-time (RT)-PCR. RESULTS: Altered expression
      of several genes involved in 5-FU resistance in CCA cell lines was observed. The
      expression levels of almost all target genes investigated including TP, DPD,
      ENT1, UNG1, TOP2A, BIRC5, TP73 and DeltaNp73 appeared to be significantly altered
      in these resistant strains. The expression of the TS gene tended to be increased
      but the fold change was not significantly different from their parental cell
      lines. UNG1 (a DNA repairing enzyme) and BIRC5 (an apoptotic inhibitor)
      expressions were increased whereas TP73 (a proapoptotic factor) expression levels
      decreased concomitantly. CONCLUSION: Our study showed that increases in UNG1 and
      BIRC5 expression and concomitant decreases in TP73 expression may be associated
      with development of acquired 5-FU resistance in CCA lines and their phenotypes.

PMID- 18714156
TI  - Cardiac impact of long-term endurance training: negligible or negative?

PMID- 18714157
TI  - Inhibition of hydroxyapatite dissolution by ovalbumin as a function of pH,
      calcium concentration, protein concentration and acid type.
AB  - Hydroxyapatite is the main constituent of the dental hard tissues, and in vivo
      its dissolution in acids leads to the pathological condition of dental erosion.
      Food proteins which inhibit hydroxyapatite dissolution may find application as
      erosion-reducing agents in food and drink products. The aim of this study was to
      investigate the egg protein ovalbumin as a potential inhibitor of hydroxyapatite
      dissolution in acidic solutions, with conditions representative of dental
      erosion. The dissolution rate of hydroxyapatite discs was measured in an acidic
      solution as a function of pH, calcium concentration, ovalbumin concentration and
      acid type. All experiments were performed in triplicate. 0.2% w/v ovalbumin
      significantly reduced the dissolution rate in citric acid by 50-75% over the pH
      range 2.80-4.00, and by 45-60% in solutions with calcium concentrations of up to
      20 mM (p < 0.05). The effect was persistent for several rinses after the initial
      exposure to the protein. 0.02% w/v ovalbumin significantly reduced the
      dissolution of hydroxyapatite in citric acid by 30-55%. Ovalbumin did not,
      however, statistically significantly reduce the hydroxyapatite dissolution rate
      in malic or lactic acids. The effect is ascribed to adsorption and partial,
      reversible denaturation of ovalbumin on the hydroxyapatite surface. There may be
      some interaction between ovalbumin and the citrate ion which promotes the
      adsorption of protein in the presence of citric acid. Ovalbumin shows promise as
      a potential erosion-reducing additive to citrus-based drinks.

PMID- 18714159
TI  - Homogeneous blue pattern in an acral congenital melanocytic nevus.
AB  - Dermoscopy in acquired acral melanocytic nevi has been widely studied. This is in
      contrast with the little information about the dermoscopic characteristics in
      congenital acral melanocytic nevi. We report a 46-year-old man who was referred
      due to a lesion on his right sole present since childhood corresponding to an
      acral congenital nevus. Dermoscopy showed a homogeneous blue pattern not
      previously described in acral benign tumors. The homogeneous blue pattern has
      previously been associated with blue nevus and skin metastasis of melanoma. The
      recognition of this pattern in benign acral congenital nevi is relevant in the
      clinical decision making concerning acral tumors.

PMID- 18714158
TI  - Self-reported adherence to treatment and quality of life in mild to moderate
      acne.
AB  - BACKGROUND: Adherence to treatment is a mayor issue in dermatology, and its
      relationship to quality of life has barely been studied. OBJECTIVE: To evaluate
      the relationship between scores on the Skindex-29 skin disease assessment scale
      and adherence to treatment in patients with acne. METHODS: An observational,
      prospective study of 1,628 patients carried out by 252 clinicians in Spain.
      RESULTS: Adherence was related to better objective and subjective severity index
      scores and better Skindex-29 scale scores at the end of the study. Young, male
      and unemployed patients had the worst adherence scores. Baseline and final
      Skindex-29 scale scores were significantly worse in non-adherent females, while
      non-adherent males scored better. Reasons for non-adherence were side effects for
      older patients and forgetfulness for younger ones. CONCLUSION: Dermatologists
      should explain that adherence to treatment is linked to better outcomes and
      better quality of life. Young females with high Skindex-29 scale scores and males
      with low Skindex scores are especially prone to non-adherence.

PMID- 18714160
TI  - Generalized telangiectasia: a manifestation of intravascular B-cell lymphoma.

PMID- 18714161
TI  - Inhibition of apoptotic signaling and neointimal hyperplasia by tempol and nitric
      oxide synthase following vascular injury.
AB  - OBJECTIVES: We hypothesized that redox-mediated apoptosis of medial smooth muscle
      cells (SMC) during the acute phase of vascular injury contributes to the
      pathophysiology of vascular disease. METHODS: Apoptosis of medial SMC (1-14 days
      following balloon injury) was identified in rat carotid arteries by in situ DNA
      labeling. NADPH-derived superoxide and expression of Bcl-xL, Bax, caspase-3 and
      caspase-9 were assessed. The antioxidant tempol was administered in drinking
      water throughout the experimental period, and local adenoviral-mediated gene
      transfer of eNOS was performed prior to vascular injury. RESULTS: Balloon injury
      increased NADPH-dependent superoxide production, medial SMC apoptosis, Bax
      positive medial SMC index, Bax/Bcl-xL ratio, and caspase-3 and caspase-9
      expression in the injured arteries. Treatment with tempol or eNOS gene transfer
      decreased superoxide levels and medial SMC apoptosis, with a concomitant increase
      in medial SMC density. Inhibition of superoxide was associated with a decreased
      Bax/Bcl-xL ratio, and caspase-3 and -9 expression. Tempol treatment and eNOS gene
      therapy significantly reduced neointima formation. CONCLUSION: Vascular
      generation of reactive oxygen species participates in Bax activation and medial
      SMC apoptosis. These effects likely contribute to the shedding of cell-cell
      adhesion molecules and promote medial SMC migration and proliferation responsible
      for neointimal hyperplasia.

PMID- 18714163
TI  - Prolongation of survival and improvement in performance status following
      palliative chemotherapy in gastrointestinal cancer patients with a poor
      performance status.
AB  - BACKGROUND: The prognosis of advanced gastrointestinal cancer, especially in
      patients with poor performance status (PS), is generally dismal. Patients with PS
      3-4 are almost ineligible for participation in clinical studies. PATIENTS AND
      METHODS: From June 2000 to February 2007, 116 patients with poor PS (PS 3 = 73
      and PS 4 = 43) were treated with chemotherapy. Retrospective analysis was
      performed. RESULTS: Of the 107 patients with at least one measurable lesion, a
      partial response was obtained in 15 patients (14.0%). Of 65 patients with ascites
      and/or pleural effusion, 12 patients achieved decreased fluid accumulation. A
      decline in tumor markers was observed in 30 patients. As a result, 38 patients
      (32.7%) achieved tumor response, a decrease in fluid accumulation or a decline in
      tumor markers (responders), which resulted in a survival benefit compared to the
      other 78 patients without effect (6.9 vs. 2.2 months, p < 0.001). PS improvement
      was seen in 16 patients (13.8%). CONCLUSIONS: The results suggest that
      chemotherapy may be beneficial in gastrointestinal cancer patients with poor PS,
      as demonstrated by a certain degree of improvement in PS and survival in
      responders. Further study is required to confirm the benefit of chemotherapy in
      this patient population.

PMID- 18714164
TI  - Locoregionally advanced nasopharyngeal carcinoma: induction chemotherapy with
      cisplatin and 5-fluorouracil followed by radiotherapy and concurrent cisplatin: a
      phase II study.
AB  - BACKGROUND: Chemoradiotherapy is the current standard of care for locoregionally
      advanced nasopharyngeal carcinoma. The purpose of this study was to assess the
      feasibility and efficacy of induction chemotherapy (CHT) followed by concomitant
      chemoradiotherapy in this patient population. PATIENTS AND METHODS: In this
      single-arm, phase II study, patients with locoregionally advanced nasopharyngeal
      carcinoma were treated with 3 cycles of induction CHT with cisplatin (100 mg/m(2)
      on day 1) and 5-fluorouracil (1,000 mg/m(2) continuous infusion on days 1-4)
      followed by 3 cycles of cisplatin (100 mg/m(2) on days 1, 22 and 43) and
      concurrent radiotherapy up to 70 Gy. The primary endpoint was objective response.
      RESULTS: Thirty-four patients were enrolled, and all completed both induction
      treatment and subsequent chemoradiotherapy. Objective response rates were 79.4%
      (95% CI 62.1-91.3) and 85.3% (95% CI 68.9-95.0) after induction CHT and
      chemoradiation, respectively. Treatment was well tolerated and toxicity was
      manageable. At a median follow-up of 29 months, 3-year overall survival and
      progression-free survival rates are 80.0% (95% CI 0.64-0.95) and 54.0% (95% CI
      0.36-0.73), respectively. CONCLUSIONS: Induction CHT with cisplatin and 5
      fluorouracil followed by concomitant chemoradiotherapy is a feasible and active
      regimen for patients with stage IIB-IVB nasopharyngeal carcinoma. This regimen
      resulted in excellent locoregional disease control and overall survival.

PMID- 18714162
TI  - ALS2/alsin knockout mice and motor neuron diseases.
AB  - Autosomal recessive mutations in the ALS2 gene have been linked to juvenile-onset
      amyotrophic lateral sclerosis (ALS2), primary lateral sclerosis and juvenile
      onset ascending hereditary spastic paraplegia. Except for two recently identified
      missense mutations, all other mutations in the ALS2 gene lead to a premature stop
      codon and likely abrogate all the potential functions of alsin, the protein
      encoded by the ALS2 gene. To study the pathologic mechanisms of ALS2 deficiency,
      four different lines of ALS2 knockout (ALS2(-/-)) mice have been generated by
      independent groups. The loss of ALS2/alsin does not have a drastic effect on the
      survival or function of motor neurons in mice. However, subtle deficits observed
      in the behavior and pathology of these mice have aided in our understanding of
      the relationship between alsin and motor neuron dysfunction. In this review, we
      summarize and reconcile major findings of ALS2(-/-) mice and attempt to place
      these results within the larger context of modeling recessive movement disorders
      in mice.

PMID- 18714165
TI  - Multifocal Epstein-Barr virus-associated smooth muscle tumor in adults with AIDS:
      case report and review of the literature.
AB  - OBJECTIVES: The aim of this study was to provide a systematic review of Epstein
      Barr virus-associated smooth muscle tumors (EBV-SMT) in human immunodeficiency
      virus (HIV)-infected adults, focusing on clinical and histopathologic features
      and outcome. METHODS: A literature search was performed using Medline, Embase and
      the Cochrane Library. RESULTS: We reviewed 35 cases including our case of a
      patient with a progressive multifocal EBV-SMT. Patients were mainly men (n = 24)
      with a mean age of 35.5 years. Median CD4 count was 21/mm(3). Main locations were
      brain (n = 12), liver (n = 8), spinal cord (n = 7) and adrenal gland (n = 6). The
      tumors were multifocal in 34% of cases, whereas analysis of clonality showed
      different clones in tumors from different sites. Treatment included removal
      surgery in 17 cases and/or radiotherapy in 9 and therapeutic abstention in 4.
      Mean follow-up after diagnosis was 12.3 months. Nine patients died during this
      period essentially from opportunistic infection and only 2 from the disease.
      CONCLUSION: EBV-SMT should be added to the list of virally induced tumors in
      severely immunocompromised HIV-infected adults. Multifocality of independent
      tumor clones, especially in liver, brain, spinal cord and adrenal gland, and a
      slow disease progression seem to be the key features of these tumors, the
      treatment of which remains poorly defined.

PMID- 18714166
TI  - Participation in clinical trials as viewed by the patient: understanding cultural
      and emotional aspects which influence choice.
AB  - BACKGROUND: Patients invited to take part in a clinical trial may evoke an
      archetype on which they may base their decision of adherence to participation,
      instead of on the study itself. METHODS: A 17-item, multiple choice questionnaire
      was developed, tested and then administered to 102 Italian-speaking patients with
      advanced lung or breast cancers who had never been exposed to participation in a
      trial. RESULTS: The questionnaire was answered by all patients. Eighty-five
      percent were positive about trial participation. Demographic factors did not
      influence patients' willingness to participate. Trust in the investigator (76%)
      or in the institute (64%) and hope of receiving a new chance for cure (78%) were
      cited as reasons to accept participation. A minority was concerned by potential
      conflicts of interest (31%) or the thought of being 'guinea pigs' (36%), and
      feared that doctors were interested in advancing their own research, even though
      there were more efficient drugs available (28%). Fifty percent feared receiving a
      little-known medicine, and 76% considered that a thorough explanation of
      toxicity/safety of the proposed treatment helped them decide. CONCLUSION: Several
      prejudices, fears and some hopes have been captured by the questionnaire.
      Understanding such specifics will improve patient information leading patients to
      a more conscious motivation in deciding whether to participate in a clinical
      trial.

PMID- 18714168
TI  - Silencing of polo-like kinase (Plk) 1 via siRNA causes inhibition of growth and
      induction of apoptosis in human esophageal cancer cells.
AB  - Esophageal cancer ranks among one of the most frequent causes of cancer death in
      the world. Polo-like kinase 1 (Plk1) is overexpressed in human tumors and has
      prognostic value in many cancers including esophageal cancer, indicating its
      potential as a therapeutic target. In this study, we investigated the therapeutic
      potential of Plk1 in esophageal cancer using the technique of RNA silencing via
      small interfering RNA (siRNA). Synthetic siRNA duplexes against Plk1 were
      introduced into 4 esophageal cancer cell lines, which subsequently resulted in a
      significant inhibition in Plk1 expression in the cells. We found that the
      targeted depletion of Plk1 caused a dramatic mitotic catastrophe (mitotic cell
      cycle arrest as well as defects in several mitotic events such as incomplete
      separation of sister chromatids and failure of cytokinesis) followed by massive
      apoptotic cell death, and eventually resulted in a significant decrease in growth
      and viability of all 4 esophageal cancer cell lines studied. In addition, our
      results also indicated that the mitotic arrest induced by Plk1 depletion is
      mediated by the inactivation of the cdc2/cyclin B1 complex. Taken together, our
      study strongly suggests that Plk1 may serve as a potential therapeutic target in
      human esophageal cancer.

PMID- 18714167
TI  - Synergism of CPT-11 and Apo2L/TRAIL against two differentially sensitive human
      colon tumor xenografts.
AB  - OBJECTIVE: The ability to sustain and grow portions of human tumors as xenografts
      in SCID mice provides a valuable preclinical opportunity to test the response of
      human tumors to treatments, both individually and in combination. Using this
      model, our laboratory has previously demonstrated that the growth of several
      human adenocarcinomas can be inhibited by Apo2L/TRAIL. Apo2L/TRAIL triggers
      apoptosis in many types of tumor cells, and when combined with various
      chemotherapeutic agents results in enhanced inhibition of tumor growth in many
      xenograft models. METHODS: To gain further insight into the antitumor potential
      of Apo2L/TRAIL in combination with chemotherapy, we compared the responses of 2
      human colon adenocarcinomas, both of which were sensitive to CPT-11 while one was
      sensitive and the other comparatively resistant to Apo2L/TRAIL. RESULTS: In both
      cases, a greater degree of growth inhibition was achieved when these agents were
      used in combination. Western blot analysis demonstrated that in the Apo2L/TRAIL
      sensitive tumor total cellular expression of Apo2L/TRAIL death receptors (DR4 and
      DR5) as well as protein expression of the pro-apoptotic molecule BAX were higher
      and the anti-apoptotic molecule Bcl-2 was lower in comparison to the Apo2L/TRAIL
      resistant tumor. CONCLUSION: These results indicate that both Apo2L/TRAIL
      sensitive and -resistant colon tumors will respond to a combination of CPT-11 and
      Apo2L/TRAIL and predict that this will be useful in the treatment of human colon
      cancers in a clinical setting.

PMID- 18714169
TI  - Comorbidity in disease-free survivors of cervical cancer compared with the
      general female population.
AB  - OBJECTIVES: We aimed to investigate the prevalence of comorbidities in cervical
      cancer survivors compared with the general population and to identify risk
      factors and impact on their quality of life (QoL). METHODS: 860 female cervical
      cancer survivors enrolled at six tertiary hospitals and 994 women from the
      general population were surveyed on current comorbidities and QoL (EORTC QLQ-C30
      and QLQ-CX24). RESULTS: Compared with the general female population, the cervical
      cancer survivors reported higher prevalence of comorbidities (0.93 +/- 2.91 vs.
      0.37 +/- 0.67, p < 0.01), significantly more heart disease (adjusted odds ratio
      (aOR), 2.64; 95% confidence interval (CI), 1.38-5.07), liver disease (aOR, 3.29;
      95% CI, 1.54-7.02), hypertension (aOR, 1.72; 95% CI, 1.30-2.27), gastrointestinal
      disease (aOR, 1.79; 95% CI, 1.37-2.33) and musculoskeletal disease (aOR, 1.94;
      95% CI, 1.45-2.59). Heart and renal disease significantly influenced QoL in many
      subscales. Patients with diabetes or cerebrovascular disease had an increased
      likelihood of sexual problems. CONCLUSIONS: The cervical cancer survivors had
      more comorbidities than the general population, and that in turn affected their
      QoL. Vigilant follow-up of comorbidities should be incorporated into in the care
      of cancer survivors.

PMID- 18714170
TI  - Prospective comparison of sorafenib and sunitinib for second-line treatment of
      cytokine-refractory kidney cancer patients.
AB  - OBJECTIVES: It was the aim of this study to investigate the clinical differences
      between the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib as second
      line treatment for cytokine-refractory kidney cancer patients. METHODS: Twenty
      consecutive patients received continuous treatment of oral sorafenib at a dose of
      400 mg twice daily in 6-week cycles. Sunitinib was administered to the remaining
      20 patients at 50 mg once daily in repeated 6-week cycles consisting of daily
      therapy for 4 weeks, followed by a 2-week off-treatment period. We correlated
      best treatment responses and progression-free survival (PFS) with either TKI
      treatment. Adverse events were evaluated and differences were compared between
      both treatment groups. RESULTS: In the sorafenib group, 2 (10%) patients showed a
      partial response (PR) and 4 (20%) patients had progressive disease (PD) versus 6
      (30%) PRs and 3 (15%) PDs in the sunitinib group, respectively (p = 0.195). The
      median PFS was 6.4 months for sorafenib and 7.4 months for sunitinib (p = 0.969).
      In contrast to gender, age and the number of prior cytokine therapy cycles, the
      Eastern Cooperative Oncology Group performance status (p = 0.024) and the
      Memorial Sloan-Kettering Cancer Center risk groups for second-line treatments (p
      = 0.015) were independent predictive parameters of PFS. Gastrointestinal symptoms
      were found to occur with greater frequency in the sunitinib group (p = 0.03).
      CONCLUSIONS: Both TKIs showed comparable clinical benefits. The Eastern
      Cooperative Oncology Group performance status and the Memorial Sloan-Kettering
      Cancer Center risk groups can help determine which patients might benefit from
      alternative drug treatments.

PMID- 18714171
TI  - Prednisone plus gefitinib versus prednisone plus placebo in the treatment of
      hormone-refractory prostate cancer: a randomized phase II trial.
AB  - BACKGROUND: Abnormal epidermal growth factor receptor expression and pre-clinical
      data prompted us to investigate the activity of gefitinib, a selective epidermal
      growth factor receptor tyrosine kinase inhibitor, in hormone-refractory prostate
      cancer. METHODS: Eighty-two patients were randomly assigned to receive prednisone
      plus gefitinib (pG; n = 44) or prednisone plus placebo (ppl; n = 38). On
      progression, patients initially assigned to placebo were offered the possibility
      to receive gefitinib. Best prostate-specific antigen response was the primary
      endpoint. RESULTS: At a median follow-up time of 29.0 months (26.0-32.0), 77
      patients progressed and 51 died. Prostate-specific antigen response was recorded
      in 6/38 (15.8%; 95% CI 4.2-27.4) and in 5/44 (11.4%; 95% CI 2.0-20.8) patients in
      pG and ppl groups, respectively. There was no difference between groups in time
      to progression (median pG 4.0 months, range 3.5-4.5; median ppl 4.5 months, range
      3.5-5.0) and survival (median pG 26.5 months, range 16.0-37.0; median ppl 20.5
      months, range 14.0-27.0). Adverse events occurred in 19 patients in each arm and
      were generally mild. CONCLUSIONS: pG showed a good tolerability profile but only
      a limited therapeutic activity in hormone-refractory prostate cancer.

PMID- 18714172
TI  - Age-related macular degeneration and mortality: the Beijing eye study.
AB  - PURPOSE: To assess the association between age-related macular degeneration (AMD)
      and mortality in a population-based setting. PROCEDURES: At baseline in 2001, the
      Beijing Eye Study examined 4,378 subjects for AMD with a detected frequency of
      110/4,378 (2.5%) subjects for early AMD and of 12/4,378 (0.3%) subjects for late
      AMD. In 2006, all study participants were re-invited for a follow-up examination.
      RESULTS: Out of the 4,378 subjects, 3,218 (73.5%) returned for a follow-up
      examination while 138 (3.2%) were dead and 1,022 (23.3%) did not agree to be re
      examined or had moved away. Early AMD and late AMD were not significantly
      associated with mortality (p = 0.40 and 0.33, respectively), neither in
      univariate analysis nor in multivariate analysis. CONCLUSIONS: AMD may not be
      associated with an increased mortality in adult Chinese.

PMID- 18714173
TI  - 'Mentoring is about inspiring interest and excitement in others'. An interview
      with Charles Frey, MD, Professor Emeritus, University of California, Davis,
      Calif., USA. Interview by Martin E. Fernandez-Zapico.
AB  - Prof. Charles Frey led the way in the field of therapeutic approaches in
      pancreatic diseases by developing one of the most frequently used surgical
      operation: the Frey procedure for chronic pancreatitis. In this interview for
      Pancreatology, Prof. Frey shares his life experiences as a pancreatologist and
      provides advice to young pancreatic researchers.

PMID- 18714174
TI  - Patient advocacy.
AB  - Regardless of the treatment regimens and ongoing research we do as medical
      doctors and scientists, our bottom line is to improve the lives of those
      suffering from pancreatic cancer; certainly not an easy undertaking. In a
      previous issue of Pancreatology (April 2008, vol. 8), our editor discussed the
      importance of empathy toward our patients. In reflecting on the mission of trying
      to accomplish this goal, it is the patients, themselves, and their families who
      can offer the best insight into the quality of life of the patient. In this
      issue, the focus is on pancreatic cancer patients and their families who have
      formed foundations and websites toward the cause. Their insight should be valued
      not only for the support group they form for other patients but for medical
      doctors and researchers as well. In addition, their advocacy for this devastating
      disease is essential to our mission both in their generosity with funding and in
      their voices to our governments for more national funding in this area. The human
      factor should never be erased from our thoughts.

PMID- 18714175
TI  - Primers on molecular pathways: nuclear receptors in pancreatic cancer. The ligand
      independent way.
AB  - Nuclear receptors (NRs) are ligand-activated transcription factors that regulate
      gene expression. These receptors share a quite similar structure and mechanism of
      action. Upon ligand binding, NRs translocate from the cytoplasm to the nucleus
      and bind to specific DNA sequences that regulate expression of different genes.
      In the absence of ligand the cascade of signaling events is different and either
      activation or repression may occur. Interestingly, several NRs are implicated in
      the pathogenesis of pancreatic cancer (PanCa). Specifically, androgen and
      estrogen receptor-related pathways are active in patients with pancreatic tumors,
      thus representing a suitable target for PanCa treatment. Although anti-hormone
      treatment has a modest effect on PanCa, ligand-independent activation of NRs
      remains overall unexplored in this disease.

PMID- 18714176
TI  - Autophagy and pancreas disease.
AB  - Autophagy is an evolutionarily preserved degradation process of cytoplasmic
      cellular constituents, which has been known for its role in protecting cells
      against stresses such as starvation and in eliminating defective subcellular
      structures. It is essentially a form of self-cannibalism - hence the name that
      means 'self-eating' - in which the cell breaks down its own components. By mostly
      morphological studies, autophagy has been linked to a variety of pathological
      processes such as neurodegenerative diseases and tumorigenesis, which highlights
      its biological and medical importance. However, whether autophagy protects from
      or causes disease is unclear. Autophagic morphology was described in human
      pancreatitis by Helin et al. in 1980. Actually, acute pancreatitis is one of the
      earlier pathological processes where autophagy has been described in a human
      tissue. Autophagy, autodigestion and cell death are early cellular events in
      acute pancreatitis. The aim of this review is to introduce a description of the
      autophagic process and to discuss the possible role of autophagy in acute
      pancreatitis.

PMID- 18714177
TI  - High constant incidence rates of second primary neoplasms.
AB  - The incidence of contralateral breast cancer is high and constant with age,
      around five per 1000 women who had a primary breast cancer. For other neoplasms,
      the pattern of incidence of second primary neoplasms with age is less known,
      particularly as for only a few neoplasms the site of origin is not totally
      removed, and hence remains at risk of a second primary. Using the dataset from
      the Cancer Registry of the Swiss Canton of Vaud, we show that the incidence of
      second neoplasms is constant with age also after oral and pharyngeal, colorectal
      cancers, cutaneous malignant melanoma (CMM) and basal cell carcinoma. The
      incidence of first primary oral and pharyngeal cancer increased 20-fold between
      age 30-39 and 70-89 years, whereas the incidence of second neoplasms did not
      increase with age. Rates of second colorectal cancer remained relatively constant
      with age, between 2.5 per 1000 at age 40-59 years and 3.8 per 1000 at 70 years
      and above. Likewise, for CMM, the age-specific incidence rates of second primary
      CMM did not vary, ranging between 1 and 2.5 per 1000 in various subsequent age
      groups. The pattern of incidence for second basal cell carcinoma was similar,
      with no clear rise with age. These patterns are compatible with the occurrence of
      a single mutational event in a population of susceptible individuals. A possible
      implication of these observations is that a variable, but potentially large,
      proportion of cancers arise in very high-risk individuals and the incidence, on
      average, increases at a high constant level at a predetermined age.

PMID- 18714178
TI  - Low prevalence of CDKN2A/ARF mutations among early-onset cancers of breast,
      pancreas and malignant melanoma in Poland.
AB  - In this report the contribution of CDKN2A/ARF germline mutations to early-onset
      cancers of the breast, pancreas and malignant melanoma was examined. We screened
      66 women with breast cancer diagnosed at age 30 and below, 72 melanoma patients
      with the median age at diagnosis < or = 40 years and 51 pancreatic cancer
      patients diagnosed under the age of 50 years. In the total set of 189 patients we
      found a novel change Pro48Arg (nt 143 c > g), a novel intronic change IVS1+36 g>c
      and two common variants A148T and IVS3+29 c>g. The results of this study revealed
      a paucity of mutations in CDKN2A/ARF suggesting that in the Polish population
      this gene does not contribute significantly to early-onset breast cancer,
      pancreatic cancer and malignant melanoma.

PMID- 18714179
TI  - Downregulation of SS18-SSX1 expression by small interfering RNA inhibits growth
      and induces apoptosis in human synovial sarcoma cell line HS-SY-II in vitro.
AB  - Substantial evidence indicates that the characteristic SS18-SSX fusion gene may
      play an important role in synovial sarcoma development and progression. For
      obtaining better insights into the genetic alterations and molecular mechanisms
      involved in synovial sarcomas and for developing novel therapeutic strategies for
      this disease, we first examined the efficiency of small interfering RNAs (siRNAs)
      targeting the SS18-SSX1 fusion gene in knocking down its expression in the human
      synovial sarcoma cell line HS-SY-II, and then evaluated the effects of
      downregulation of this gene on apoptosis, apoptosis-related gene expression,
      growth regulatory proteins, and the growth of tumor cells in vitro. We observed a
      marked decrease (by more than 87.6%) in SS18-SSX1 expression levels in cells
      transfected with a plasmid expressing hairpin siRNA for this gene, which was
      accompanied by (i) reduction in protein levels of cyclin D1 and cyclin A, (ii)
      reduction in antiapoptotic protein Bcl-2 and activation of caspase 3/apoptosis,
      and (iii) growth inhibition of HS-SY-II cells in vitro. Our results demonstrate
      that siRNA targeting of SS18-SSX1 may have therapeutic potential in the treatment
      of synovial sarcomas.

PMID- 18714180
TI  - Sex and socioeconomic inequalities of lung cancer mortality in Barcelona, Spain
      and Sao Paulo, Brazil.
AB  - The objective of this paper was to assess sex and socioeconomic inequalities in
      lung cancer mortality in two major cities of Europe and South America. Official
      information on mortality and population allowed the estimation of sex- and age
      specific death rates for Barcelona, Spain and Sao Paulo, Brazil (1995-2003).
      Mortality trends and levels were independently assessed for each city and
      subsequently compared. Rate ratios assessed by Poisson regression analysis
      addressed hypotheses of association between the outcome and socioeconomic
      covariates (human development index, unemployment and schooling) at the inner
      city area level. Barcelona had a higher mortality in men (76.9/100,000
      inhabitants) than Sao Paulo (38.2/100,000 inhabitants); although rates were
      decreasing for the former (-2%/year) and levelled-off for the latter. Mortality
      in women ranked similarly (9.1 for Barcelona, 11.5 for Sao Paulo); with an
      increasing trend for women aged 35-64 years (+7.7%/year in Barcelona and
      +2.4%/year in Sao Paulo). The socioeconomic gradient of mortality in men was
      negative for Barcelona and positive for Sao Paulo; for women, the socioeconomic
      gradient was positive in both cities. Negative gradients indicate that deprived
      areas suffer a higher burden of disease; positive gradients suggest that
      prosmoking lifestyles may have been more prevalent in more affluent areas during
      the last decades. Sex and socioeconomic inequalities of lung cancer mortality
      reinforce the hypothesis that the epidemiologic profile of cancer can be improved
      by an expanded access to existing technology of healthcare and prevention. The
      continuous monitoring of inequalities in health may contribute to the concurrent
      promotion of well-being and social justice.

PMID- 18714181
TI  - Risk factors for second primary tumours in breast cancer survivors.
AB  - Breast cancer (BC) survivors have an increased risk of developing second primary
      cancer (SPC). The aim of this study was to detect and compare SPC predictors
      linked to the host, the first BC and its treatment. Two hundred and seventeen
      patients with a nonbreast SPC and 465 matched controls, nested in the cohort of
      BC patients diagnosed in a Spanish region between 1975 and 2003, were involved in
      a case-control study. The Tumour Registry database provided information about the
      host, BC and its treatment factors. Their contribution to the risk of developing
      SPC was measured by means of a conditional logistic regression. After controlling
      for differences between cases and controls at baseline, obesity [odds ratio (OR):
      7.48; 95% confidence interval (CI): 1.25-44.88], smoking (OR: 3.16; 95% CI: 1.23
      8.15), high blood pressure (OR: 1.68; 95% CI: 1.04-2.71) and having first-degree
      relatives suffering from cancer (OR: 1.69; 95% CI: 1.05-2.72) were the best SPC
      predictors. The risk of SPC increases by 1% per month of survival from BC (OR:
      1.01; 95% CI: 1.007-1.012), while having metastases (OR: 0.23; 95% CI: 0.14-0.37)
      and being premenopausal at diagnosis of the BC (OR: 0.44; 95% CI: 0.247-0.792)
      diminish the risk, probably decreasing survival. The treatments were the
      regression model's worst predictors. Controlling modifiable factors linked to
      lifestyle such as obesity and smoking is essential to prevent SPC in survivors of
      BC. Health education to remove persistent risk factors should be included in the
      treatment protocol of BC patients, because they are important predictors of SPC.

PMID- 18714182
TI  - Interval breast cancers in a community screening programme: frequency,
      radiological classification and prognostic factors.
AB  - The frequency of interval cancers (IC) can be an indicator inversely related to
      the quality of a breast screening programme. The objectives were to estimate the
      frequency of IC, to classify IC by posterior radiological review, and to describe
      the prognostic factors of these IC. The setting was the Sabadell-Cerdanyola
      Breast Cancer Screening Programme, in Northeast Spain. We developed a population
      based study of the IC occurring in the first three rounds (1995-2001). The
      indicators used were the incidence rate of invasive IC per 10 000 women screened
      and the proportional incidence, stratified by age group, type of screening and
      the round, and the time elapsed since the last screening mammogram. A
      radiological informed consensus review was used to classify the IC. No specific
      pattern of incidence rates was evident with respect to age, type of screening, or
      round, although screening was generally more sensitive in women aged 60-69 years.
      The proportional incidence for the period 0-11 months was always under 30%.
      Twenty-one percent of 38 IC evaluated (95% CI: 8.0-34.0) were attributed to
      errors in the screening process (false negatives). No major differences in the
      prognostic factors of the 57 IC were identified on examining the radiological
      type or the time since the last screening mammogram. We observed a high frequency
      of IC from 12 months after screening. It is necessary to reach a consensus
      regarding the definition and the analysis of IC and to establish mechanisms that
      would allow all the malignant tumours diagnosed in the target population to be
      identified.

PMID- 18714183
TI  - Current United Kingdom practice in the diagnosis and management of columnar-lined
      oesophagus: results of the United Kingdom National Barrett's Oesophagus Registry
      endoscopist questionnaire.
AB  - The management of the columnar-lined oesophagus (CLO) has remained controversial
      for the last 10 years, with practices varying between individual physicians and
      centres throughout the United Kingdom. Various guidelines exist, although
      international consensus over issues such as the recognition of short-segment
      disease and surveillance policies for uncomplicated and dysplastic disease is
      lacking. Questionnaires examining the practice of diagnosis and surveillance of
      CLO were sent to 41 centres spread throughout the United Kingdom. Thirty (73%)
      centres replied. Twelve (40%) had a specific written policy for the management of
      CLO. Twenty-five (83%) centres made a diagnosis of CLO in the presence of any
      length of columnarization. Twenty-seven (90%) centres surveyed CLO with 81% of
      them undertaking a selective surveillance policy. Endoscopic surveillance
      intervals were fairly consistent for uncomplicated CLO and high-grade dysplasia,
      but were less consistent for low-grade dysplasia. Results confirmed that even
      amongst centres with a specialist interest in the management of CLO, marked
      variations exist in diagnosis and surveillance practice.

PMID- 18714184
TI  - Barrett's Registries in Europe: report of an International Workshop.
AB  - A workshop on Barrett's Registries in Europe was held in Venice in February 2007
      with the aim of establishing the feasibility of joint projects. It was concluded
      that there were enough areas of similarity and common objectives for EBRA to be
      set up for future collaboration.

PMID- 18714185
TI  - The public prefers fecal occult blood test over colonoscopy for colorectal cancer
      screening.
AB  - The acceptability of colorectal cancer (CRC) screening tests to the population
      influences adherence. Population preferences between fecal occult blood test
      (FOBT) and colonoscopy for CRC screening were examined by previous test
      experience. The study population was a random sample of 413 members of Israel's
      largest Health Maintenance Organization (HMO) aged 48-68 years. In a telephone
      interview, an explanation was provided regarding FOBT and colonoscopy.
      Participants were asked which they preferred and their degree (1-6) of agreement
      with each of eight test characteristics. Overall Attitude Scores toward FOBT and
      colonoscopy were compared. Predictors of colonoscopy preference and of refusal to
      undergo screening were examined using a logistic regression model. FOBT was
      preferred as a screening test by 70.2% of the participants, colonoscopy by 9.3%,
      7.4% were indecisive, and 13.1% were not interested in screening. FOBT and
      colonoscopy similarly scored highly as life saving (5.2 vs. 5.1, respectively),
      with colonoscopy scoring significantly higher as time consuming (3.8 vs. 1.3,
      P<0.0001), disturbing (4.6 vs. 1.8, P<0.0001), painful (4.1 vs. 1.0, P<0.0001),
      annoying (4.8 vs. 1.9, P<0.0001), and involving risk (3.2 vs. 1.0, P<0.0001). In
      a logistic multivariate analysis, preference of colonoscopy was associated with
      the perception of being at CRC risk [odds ratio (OR): 3.1 (95% confidence
      interval (CI): 1.3-7.6)], with more positive attitude scores towards this test
      [OR: 2.2 (95% CI: 1.6-3.0)], and with a more negative one toward FOBT [OR: 0.4
      (95% CI: 0.3-0.7)]. Target population preferences for CRC screening supports a
      policy of FOBT screening for an average risk population and colonoscopy for high
      risk individuals.

PMID- 18714186
TI  - Serum cathepsin B and plasma urokinase-type plasminogen activator levels in
      gastrointestinal tract cancers.
AB  - Cathepsin B (CATB) and urokinase-type plasminogen activator (UPA) play an
      important part in cancer invasion and metastasis. The behavior of CATB and UPA
      has not been evaluated in the same experimental setting in different
      gastrointestinal tumors and in precancerous lesions. Serum CATB and plasma UPA
      levels were determined by enzyme-linked immunoadsorbent assay and their
      sensitivity, specificity, and diagnostic accuracy have been calculated in
      patients with colorectal (n=72), gastric (n=30), hepatocellular (n=28), and
      pancreatic cancer (n=15) as well as in gastric epithelial dysplasia (n=25),
      colorectal adenomas (n=30), and tumor-free control patients (n=44). Serum CATB
      and plasma UPA antigen concentrations were significantly higher in patients with
      cancer than in controls. When all tumors were considered, the sensitivity,
      specificity, and diagnostic accuracy of CATB (89, 86, and 89%) were higher than
      that of UPA (76, 70, and 74%). CATB demonstrated in all types of tumors a better
      diagnostic accuracy than UPA. The positive predictive values of CATB (95%) and
      UPA (89%) may suggest their use in the evaluation of patients with a suspicion of
      malignancy. CATB and UPA were significantly higher in patients with gastric
      epithelial dysplasia and colorectal adenomas than in controls. Antigen levels of
      CATB and UPA were significantly correlated in both cancers and precancerous
      lesions. At the time of clinical presentation, serum CATB and plasma UPA antigen
      levels are sensitive indicators of gastrointestinal malignancies. Determination
      of serum CATB and plasma UPA levels may be useful to identify patients at a
      higher risk for progression to cancer, who could be subjected to a more strict
      follow-up protocol.

PMID- 18714187
TI  - Methylenetetrahydrofolate reductase polymorphisms and susceptibility to gastric
      cancer in Chinese populations: a meta-analysis.
AB  - Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene are
      thought to have significant effects on folate metabolism and, thus, on cancer
      risk, but the reported results are not always consistent. In this meta-analysis
      including 2165 patients and 3279 controls, we assessed reported studies of
      associations between polymorphisms of MTHFR and susceptibility to gastric cancer
      in Chinese populations. An increased risk was found for MTHFR C677T in the meta
      analysis [odds ratio (OR): 1.42; 95% confidence interval (CI): 1.24-1.62]. No
      association resulted for MTHFR A1298C (OR: 0.95; 95% CI: 0.78-1.17). Results from
      the subgroup analyses showed an increased risk for individuals with low (OR:
      1.50; 95% CI: 1.18-1.91) versus high (OR: 1.21; 95% CI: 0.98-1.51) folate levels.
      The sensitivity analysis and publication bias diagnostics confirmed the
      reliability and stability of this meta-analysis. Overall, these findings support
      the hypothesis that folate plays a role in gastric carcinogenesis. Regarding
      cardia or noncardia gastric cancer, more studies are required for definite
      conclusions, as the number of studies is relatively small.

PMID- 18714188
TI  - Geographical relationships between sociodemographic factors and incidence of
      cervical cancer in the Netherlands 1989-2003.
AB  - In many industrialized countries, with some degree of screening, cervical cancer
      nowadays is most frequent among women of lower socioeconomic status (SES), partly
      owing to their lower participation in screening. This study aims to provide
      support for specification of mass screening policy for cervical cancer by
      describing relationships between sociodemographic factors and the incidence of
      cervical cancer in the Netherlands based on geographical differences and by
      analysing the relationship between SES of neighbourhood and individual tumour
      characteristics. Municipality-specific, age-adjusted incidence rates for cervical
      cancer were calculated from the Netherlands Cancer Registry, and data on
      sociodemographic factors were obtained from Statistics Netherlands. Logistic
      regression analysis was performed to investigate determinants of variations in
      incidence at the ecological level. An additional analysis linked individual
      tumour characteristics to SES estimates at the postal code level by calculating
      relative risks (RR). The incidence was higher in municipalities with a high
      prevalence of immigrants [odds ratios 7.9, 1.4-47 95% confidence intervals (CI)]
      and with more individuals on welfare (odds ratios 8.6, 1.7-43 95% CI). Patients
      residing in neighbourhoods with lower SES had higher Federation of Gynecology and
      Obstetrics stages (RR 1.4, 1.2-1.6 95% CI) and fewer adenocarcinomas (RR 0.7, 0.6
      0.9 95% CI), and were younger at diagnosis (P<0.001). Cervical cancer is more
      common among women of lower SES and immigrant women. This, together with the
      finding that lower SES is associated with more advanced cancer and consequently
      worse survival, emphasizes the importance of future cervical cancer prevention
      programmes targeted at women of lower SES who do not participate in opportunistic
      screening.

PMID- 18714189
TI  - Ethnicity determines association of p53Arg72Pro alleles with cervical cancer in
      China.
AB  - Minority Uigur women residing in Xinjiang, in the northwest of China, have a high
      incidence of cervical carcinoma (CC; 527/100 000) and are often diagnosed young.
      We favor the hypothesis that Uigur women may carry different genetic factor(s)
      making them more susceptible to CC than majority Han (Chinese) women living in
      the same region. Using PCR-restriction fragment length polymorphism, we
      investigated associations of a p53Arg72Pro polymorphism with CC in Uigur women
      compared with those in Han women. The study included 152 Uigur patients with CC
      and 110 controls, and 120 Han patients with CC and 122 controls. In Uigur women,
      CC was associated with p5372Arg/Arg homozygosity (chi=7.196, P<0.05) and with
      human papillomavirus-16 (chi=7.177, P<0.05). In Han women, however, CC was
      associated with p5372Pro/Pro homozygosity (chi=8.231, P<0.05). These observations
      suggest that individuals with different genetic backgrounds carry different
      susceptibilities to CC, at least in the Uigur and Han ethnic women studied in
      China.

PMID- 18714190
TI  - Low estradiol levels in women of reproductive age having low sleep variation.
AB  - Higher exposure to light at night, for example, owing to night shift work or
      decrease in sleep duration, may suppress melatonin production, which in turn may
      increase the reproductive hormone levels. High levels of steroid hormones,
      especially estrogens, may be associated with an increase of the breast cancer
      risk. This study investigated whether variation in the sleep duration during one
      entire menstrual cycle corresponds to estradiol saliva concentrations in healthy,
      urban women of reproductive age. During 2000-2001, 95 regularly menstruating
      women aged 24-36 in Poland collected daily saliva samples for one entire
      menstrual cycle. Saliva samples were analyzed for concentration of 17-beta
      estradiol (E2) using radio immunoassay. Information on the number of hours of
      sleep per night (sleep duration) was collected daily by questionnaires for one
      entire menstrual cycle. Using covariance analysis, after adjustments for sleep
      duration, we documented a positive relationship between the sleep variation
      (sleep coefficient of variation) and E2 levels in women of reproductive age. Mean
      levels of E2 differed significantly in women from the lowest sleep coefficient of
      variation quartile (13.93 pmol/l) in comparison with other quartiles (22.35
      pmol/l), (P<0.001). The low sleep variation group, that is, the women who sleep
      regularly, had mean E2 levels 60% lower than other groups. These results suggest
      that sleep variation significantly correlates with E2 levels, whereas sleep
      duration does not show a statistically significant relationship. This study
      suggests that sleep variation may influence endogenous estrogens, which is of
      importance for risk of breast cancer.

PMID- 18714191
TI  - Indoor air pollution from solid fuel use, chronic lung diseases and lung cancer
      in Harbin, Northeast China.
AB  - In some areas of China, indoor air pollution (IAP) originating principally from
      the combustion of solid fuels has a relevant role in lung cancer. Most previous
      studies focused on the female population and only a few on both the sexes. We
      analyzed the relationship between IAP from solid fuel use and selected chronic
      lung diseases and lung cancer risk in Harbin, Northeast China, an area with a
      very high base line risk of lung cancer for both the sexes. We used data from a
      case-control study conducted between 1987 and 1990, including 218 patients with
      incident, histologically confirmed lung cancer and 436 controls admitted to the
      same hospitals as cases. We calculated an index of IAP from solid fuel use
      exposure using data on heating type, cooking fuel used, and house measurements.
      Cases reported more frequently than controls an exposure to coal fuel for house
      heating and/or cooking, and the odds ratio (OR) for ever versus never exposed was
      2.19 [95% confidence interval (CI): 1.08-4.46]. The ORs of lung cancer according
      to subsequent tertiles of IAP exposure index were 1.82 (95% CI: 1.14-2.89) and
      1.99 (95% CI: 1.26-3.15) as compared with the lowest tertile. The ORs of lung
      cancer for participants with a history of chronic bronchitis and tuberculosis
      were 3.79 (95% CI: 2.38-6.02) and 3.82 (95% CI: 1.97-7.41), respectively. This
      study gives further support and quantification of the positive association
      between IAP, history of selected nonmalignant lung diseases, and lung cancer risk
      for both the sexes.

PMID- 18714192
TI  - Pediatric primary care providers and depression in community settings.

PMID- 18714193
TI  - Helping adolescents affected by war, trauma, and displacement.

PMID- 18714194
TI  - But seriously: clowning in children's mental health.

PMID- 18714195
TI  - Flexibility within fidelity.

PMID- 18714199
TI  - Lost in translation?

PMID- 18714196
TI  - Prospective study of cannabis withdrawal in cannabis-using adolescents.

PMID- 18714200
TI  - Structural abnormalities in the brainstem and cerebellum in congenital central
      hypoventilation syndrome: commentary on the article by Kumar et al. on page 275.

PMID- 18714201
TI  - Introduction of the American Pediatric Society's 2008 John Howland award
      recipient, Richard B. Johnston Jr, M.D.

PMID- 18714202
TI  - American Pediatric Society's 2008 John Howland award acceptance lecture: life
      goals for academic pediatrics.

PMID- 18714203
TI  - Insulin and insulin-like growth factor-1 increased in preterm neonates following
      massage therapy.
AB  - OBJECTIVE: To determine if massage therapy increased serum insulin and insulin
      like growth factor-1 (IGF-1) in preterm neonates. STUDY DESIGN: Forty-two preterm
      neonates who averaged 34.6 weeks (M = 29.5 wk gestational age; M birth weight =
      1237 g) and were in the "grower" (step-down) nursery were randomly assigned to a
      massage therapy group (body stroking and passive limb movements for three, 15
      minute periods per day for 5 days) or a control group that received the standard
      nursery care without massage therapy. On Days 1 and 5, the serum collected by
      clinical heelsticks was also assayed for insulin and IGF-1, and weight gain and
      kilocalories consumed were recorded daily. RESULTS: Despite similar formula
      intake, the massaged preterm neonates showed greater increases during the 5-day
      period in (1) weight gain; (2) serum levels of insulin; and (3) IGF-1. Increased
      weight gain was significantly correlated with insulin and IGF-1. DISCUSSION:
      Previous data suggested that preterm infant weight gain following massage therapy
      related to increased vagal activity, which suggests decreased stress and gastric
      motility, which may contribute to more efficient food absorption. The data from
      this study suggest for the first time that weight gain was also related to
      increased serum insulin and IGF-1 levels following massage therapy. CONCLUSION:
      Preterm infants who received massage therapy not only showed greater weight gain
      but also a greater increase in serum insulin and IGF-1 levels, suggesting that
      massage therapy might be prescribed for all growing neonates.

PMID- 18714204
TI  - Assessment of adherence to antiretroviral therapy in perinatally HIV-infected
      children and youth using self-report measures and pill count.
AB  - BACKGROUND: Parent/caregiver or child/youth self-report and pill counts are
      commonly used methods for assessing adherence to antiretroviral therapy among
      children and youth with HIV. The purpose of this study was to compare these
      different methods with one another and with viral load. METHODS: Randomly
      selected parent/caregiver and child/youth dyads were interviewed using several
      adherence self-report measures and an announced pill count was performed.
      Adherence assessment methods were compared with one another and their relative
      validity was assessed by comparison with the child's viral load close to the time
      of the interview or pill count, adjusting for primary caregiver, child age, and
      child disclosure of the diagnosis. RESULTS: There were 151 evaluable
      participants. Adherence rate by pill count was >or=90% in 52% of participants,
      was significantly associated with log(RNA) viral load (p = .032), and had
      significant agreement with viral load <400 copies/mL. However, pill count data
      were incomplete for 26% of participants. With similar proportions considered
      adherent, a variety of self-report adherence assessment methods also were
      associated with log(RNA) viral load including: "no dose missed within the past 1
      month" (p = .054 child/youth interview, p = .004 parent/caregiver interview), and
      no barrier to adherence identified (p = .085 child/youth interview, p = .015
      parent/caregiver interview). Within-rater and inter-rater agreement was high
      among self-report methods. Three day recall of missed doses was not associated
      with viral load. CONCLUSION: Findings demonstrate the validity of adherence
      assessment strategies that allow the parent/caregiver or child/youth to report on
      adherence over a longer period of time and to identify adherence barriers.
      Adherence assessed by announced pill count was robustly associated with viral
      load, but there was incomplete data for many participants.

PMID- 18714206
TI  - Children's attachment to parents and their academic functioning: sleep
      disruptions as moderators of effects.
AB  - OBJECTIVE: We investigated the amount and quality of children's sleep as a
      moderator of relations between attachment to parents and child academic
      functioning. METHOD: Data were from a sample of 166 third graders in the
      Southeastern USA. Children reported on the security of their attachments to both
      mothers and fathers, and standard assessments of academic achievement were
      obtained from schools. Children completed questionnaire measures of subjective
      sleep problems and their sleep was assessed objectively via actigraphs worn for
      seven consecutive nights. RESULTS: Attachment insecurity was associated with
      lower math achievement for children with objective sleep problems (lower quantity
      and efficiency). CONCLUSION: Findings suggest that better sleep ameliorates the
      risk for academic performance difficulties associated with insecure attachments
      to parents, and functions as a protective factor in this context.

PMID- 18714205
TI  - The impact of medical comorbidity on mental health and functional health outcomes
      among children with anxiety disorders.
AB  - OBJECTIVE: Medical comorbidity is common among children with anxiety disorders;
      however, little is known about the impact of such comorbidity on mental and
      functional health outcomes. Even less is known about these problems in high-risk
      samples of youth. METHOD: Participants in this study were youth with at least one
      anxiety disorder with a physical illness (N = 77) or without a physical illness
      (N = 73), as well as youth with at least one physical illness (but no anxiety
      disorder) (N = 438). These youth were recruited as part of the Patterns of Care
      study in which the original set of participants (N = 1715) were randomly sampled
      from one of five public sectors of care (e.g., juvenile justice, child welfare,
      mental health, alcohol and substance use services, school services for children
      with serious emotional disturbance) in San Diego County. Psychiatric diagnoses
      were assessed with a structured interview and three standardized measures were
      used to assess child health, emotional, and behavior functioning. RESULTS: At
      least half of children with anxiety disorders had a comorbid physical illness.
      Allergies and asthma were the most common comorbid physical illnesses. Children
      with anxiety disorders who had a comorbid physical illness exhibited greater
      levels of emotional problems, more somatic complaints, and more functional
      impairment than anxious children without a physical illness as well as than
      children with physical illness alone. Parents of children in the comorbid group
      also reported greater caregiver strain than the other two groups. CONCLUSIONS:
      Children with anxiety disorders have high rates of chronic illnesses such as
      asthma and allergies. These children experience considerable impairment and
      likely have unique needs that may complicate usual care.

PMID- 18714207
TI  - Nighttime sleep and daytime nap patterns in school age children with and without
      asthma.
AB  - OBJECTIVE: This research examines subjective and objective report of naps and
      nighttime sleep in 9- to 11-year-old children with and without asthma. METHODS:
      This between subjects study collected prospective self-report diary and objective
      actigraphy measures of sleep from 27 children with and 27 without asthma during a
      7-day/6-night at-home monitoring period. RESULTS: Thirty-two percent of
      participants reported daytime naps. Nappers were more likely to be children with
      asthma (12/27 vs. 5/27, p = 0.04) even though the children with asthma did not
      report being more tired, sleepy, or less alert in the morning. Nappers did not
      differ from non-nappers on self-report measures of overall sleep quality or
      number of awakenings but were documented, via objective measures, to have later
      (clock time: 23:05 vs. 22:21, p = 0.04) and more variable (Levine's Test for
      Equality of Variances: F = 10.68, p = 0.002) sleep onset times than non-nappers.
      Sleep offset times did not differ between the nappers vs. non-nappers, therefore,
      nappers had fewer total minutes of nighttime sleep than did the non-nappers (437
      vs. 465, p = 0.04). Later (clock time: 23:01 vs. 22:15, p = 0.01) sleep onset
      times were also documented in minority vs. Caucasian children. CONCLUSIONS:
      Napping appears a more common behavior than expected especially in children with
      asthma or of minority ethnicity but the reasons are unclear. Self-report measures
      may not capture important sleep characteristics that objective measures can
      identify. Strategies to reduce late and variable bedtimes of all children are
      needed given our awareness of the negative cognitive, emotional, and behavioral
      consequences of poor sleep in children.

PMID- 18714208
TI  - Maternal depressive symptoms and physical activity in very low-income children.
AB  - OBJECTIVE: To test the contribution of maternal depression during late infancy to
      physical activity in children 5 years later. METHOD: Children (n = 168) from very
      low-income households in semiurban Mexico were assessed as toddlers (15 months,
      Time 1) and at pre-school age (4-6 years, Time 2). Child low activity level (<20
      minutes of activity daily for <7 d/wk) at Time 2 was the primary outcome measure
      and maternal depressive symptoms (Center for Epidemiologic Studies-Depression
      Scale) by self-report at Time 1 was the primary independent variable. Covariates
      tested included child age, sex, BMI percentile, television viewing and behavior
      (Behavior Problem Index subscales), current maternal depressive symptoms, age,
      BMI and physical activity level, and family socioeconomic status; all covariates
      were assessed at Time 2 except for socioeconomic status. RESULTS: At 4 to 6 years
      old, 27.5% of children were categorized with low activity level. Exposure to high
      maternal depressive symptoms at child age 15 months was associated with an
      increased risk of having a low activity level at age 4 to 6 years (OR, 2.38; 95%
      CI, 1.05-5.40); results were unchanged with the inclusion of current maternal
      depressive symptoms. High child TV viewing was significantly associated with low
      activity level (OR, 5.44; 95% CI, 2.06-14.3), but did not change the effect of
      maternal depressive symptoms in early childhood. Tests of mediation revealed that
      current child internalizing behavior, but not externalizing behavior,
      significantly attenuated the association between early high maternal depressive
      symptoms and later childhood activity level. CONCLUSION: Exposure to maternal
      depressive symptoms in late infancy is a risk factor for low activity level in
      later childhood and the association may be mediated by child internalizing
      factors.

PMID- 18714209
TI  - Indulgent feeding style and children's weight status in preschool.
AB  - PURPOSE: The primary aim of this study was to examine whether parent affect and
      child temperament characteristics differ across feeding styles in low-income
      families, given suggestive evidence. The secondary aim was to examine whether
      feeding styles were still related to children's body mass index independent of
      parent affect, child temperament, and known correlates. METHODS: Participants in
      this study were 718 parents of children attending Head Start programs across two
      sites (Texas and Alabama). Parents were categorized into feeding styles of
      authoritative (n = 118), authoritarian (n = 219), indulgent (n = 240) and
      uninvolved (n = 141) using a parent-report questionnaire characterizing feeding
      in a general parenting paradigm. Parents completed questionnaires and measured
      height and weight was obtained from parents and children. RESULTS: Differences
      were found across feeding styles on parent affect and child temperament
      characteristics. Indulgent parents reported lower Negative Affect for themselves
      and lower Negative Affectivity for their children. The indulgent feeding style
      was significantly associated with higher child body mass index after controlling
      for parent affect, child temperament, and correlates (ethnicity, child age,
      parent body mass index). CONCLUSIONS: The results of this study not only show a
      robust association between the indulgent feeding style and weight status of low
      income preschool children, but also suggest how congruence between parent
      emotional affect and child temperament characteristics may contribute to excess
      consumption among children of indulgent parents.

PMID- 18714210
TI  - Violent adolescents and their educational environment: a multilevel analysis.
AB  - OBJECTIVE: This study examined the respective roles of personal and environmental
      factors in youth violence in a nationally representative sample of 7548
      postmandatory school students and apprentices ages 16-20 years in Switzerland.
      METHODS: Youth violence was defined as having committed at least one of the
      following in the previous 12 months: attacking an adult, snatching something,
      carrying a weapon, or using a weapon in a fight. Different ecological levels were
      tested, resulting in a three-level model only in males (individual, classroom,
      and school) as the low prevalence of female violence did not allow for a
      multilevel analysis. Dependent variables were attributed to each level. For
      males, the classroom level (10%) and the school level (24%) accounted for more
      than one third in interindividual variance. RESULTS: Factors associated with
      violence perpetration in females were being a victim of physical violence and
      sensation seeking at the individual level. In males, practicing unsafe sex,
      sensation seeking, being a victim of physical violence, having a poor
      relationship with parents, being depressed, and living in a single-parent
      household at the individual level; violence and antisocial acts at the classroom
      level; and being in a vocational school at the school level showed a correlation
      with violence perpetration. CONCLUSION: Interventions at the classroom level as
      well as an explicit school policy on violence and other risk behaviors should be
      considered a priority when dealing with the problem of youth violence.
      Furthermore, prevention should take into account gender differences.

PMID- 18714211
TI  - An examination of strength and concentric work ratios during variable range of
      motion training.
AB  - Variable range of motion (ROM) training consists of partial ROM resistance
      training with the countermovement being performed at a different phase of the
      movement for each set. In this study, we assessed the effect of this method of
      training on peak force, load lifted, and concentric work performed. Six male
      subjects with resistance training backgrounds (age 20.2 +/- 1.3 years, height
      179.4 +/- 4.6 cm, weight 89.6 +/- 9.9 kg, 6-repetition maximum [6RM] bench press
      92.5 +/- 14.3 kg) participated in this study. Testing consisted of 6RM bench
      press strength tests during full (FULL), three quarter ((3/4)), one half ((1/2)),
      and one quarter ((1/4)) ROM from full elbow extension bench press performed on a
      Smith machine. The 6RM load, peak force (PF), and concentric work (W) performed
      during each ROM was examined using a one-way analysis of variance performed at an
      alpha level of p < 0.05. The 6RM load increased significantly as the ROM was
      decreased for all tests (FULL = 92.5 +/- 14.3 kg, (3/4) = 102.1 +/- 14.3 kg,
      (1/2) = 123.3 +/- 23.6 kg, (1/4) = 160.9 +/- 26.2 kg). PF during each test was
      significantly higher during the (1/4) (1924.8 +/- 557.9 N) and (1/2) (1859.4 +/-
      317.1 N) ROM from full elbow extension bench press when compared with the (3/4)
      (1242.2 +/- 254.6 N) and FULL (1200.5 +/- 252.5 N) ROM exercise. Although higher
      force levels were evident, the restriction in barbell displacement resulted in a
      subsequent reduction in W as the lifting ROM was reduced. These results suggest
      that variable ROM resistance training results in increased force production as
      the ROM diminishes.

PMID- 18714212
TI  - The role of elastic energy in activities with high force and power requirements:
      a brief review.
AB  - The purpose of this article is to provide strength and conditioning practitioners
      with an understanding of the role of elastic energy in activities with high force
      and power requirements. Specifically, the article covers 1) the nature of
      elasticity and its application to human participants, 2) the role of elastic
      energy in activities requiring a stretch-shorten cycle such as the vertical jump,
      3) the role of muscular stiffness in athletic performance, 4) the control of
      muscular stiffness through feedforward and feedback mechanisms, and 5) factors
      affecting muscular stiffness. Finally, practical applications are provided. In
      this section, it is suggested that the storage and reuse of elastic energy is
      optimized at relatively higher levels of stiffness. Because stiffness decreases
      as fatigue ensues as well as with stretching before an event, the article
      emphasizes the need for proper preparation phases in a periodized cycle and the
      avoidance of long static stretches before high-force activities. The importance
      of teaching athletes to transition from eccentric to concentric movements with
      minimal time delays is also proposed due to the finding that time delays appear
      to decrease the reuse of elastic energy. In addition to teaching within the
      criterion tasks, evidence is provided that minimizing transitions in plyometric
      training, a technique demonstrated to increase musculotendinous stiffness, can
      optimize power output in explosive movements. Finally, evidence is provided that
      training and teaching programs designed to optimize muscular stiffness may
      protect athletes against sports-related injuries.

PMID- 18714213
TI  - The impact of electronic mail versus print delivery of an exercise program on
      muscular strength and aerobic capacity in people with type 2 diabetes.
AB  - Previous research indicates that the Internet, electronic mail (e-mail), and
      printed materials can be used to deliver interventions to improve physical
      activity in people with type 2 diabetes. However, no studies have been conducted
      investigating the effect of e-mail or print delivery of an exercise program on
      muscular strength and aerobic capacity in people with type 2 diabetes. The
      purpose of this clinical trial was to investigate the impact of e-mail vs. print
      delivery of an exercise program on muscular strength and aerobic capacity in
      people with type 2 diabetes. Nineteen participants with type 2 diabetes were
      allocated to either a group that was delivered a prescribed exercise program
      using e-mail (e-mail group, n = 10) or a group that was delivered the same
      prescribed exercise program in print form (print group, n = 9). Chest press and
      leg press estimated one-repetition maximum (1-RM) scores as well as estimated
      peak oxygen uptake ([latin capital V with dot above]O2peak) were measured at
      baseline and follow-up. Intention-to-treat analysis indicated significant
      improvements in chest press (mean = 7.00 kg, p = 0.001, effect size = 2.22) and
      leg press (mean = 19.32 kg, p = 0.002, effect size = 1.98) 1-RM scores and [latin
      capital V with dot above]O2peak (mean = 9.38 mL of oxygen uptake per kilogram of
      body mass per minute, p = 0.01, effect size = 1.45) within the e-mail group.
      Within the print group, significant improvements in chest press (mean = 9.13 kg,
      p = 0.01, effect size = 1.49) and leg press (mean = 16.68 kg, p = 0.01, effect
      size = 1.31) 1-RM scores and [latin capital V with dot above]O2peak (mean = 5.14
      ml of oxygen uptake per kilogram of body mass per minute, p = 0.03, effect size =
      1.14) were found. No significant between-group differences in improvements were
      found. Clinicians can deliver a prescribed exercise program, either by e-mail or
      in print form, to significantly improve muscular strength and aerobic capacity in
      people with type 2 diabetes, and expect similar outcomes.

PMID- 18714214
TI  - Undulation training for development of hierarchical fitness and improved
      firefighter job performance.
AB  - Firefighters routinely encounter physical demands that contribute to countless
      musculoskeletal injuries. Seemingly, a progressive prescription for fitness would
      offer superior protection against intrinsic job risks. The purpose of this study
      was to investigate the influence of two resistance training interventions on
      fitness adaptations among firefighters, and to assess the degree of transfer to
      job-specific tasks. Firefighter trainees were recruited for participation in this
      experimental study. Two distinct, periodized training models-undulation training
      (UT; n = 7) and standard training control (STCo; n = 7)-were used to determine
      the differential affects for muscular fitness and transference to firefighter
      performance batteries. Specific tests were administered to evaluate 1) upper- and
      lower-body muscular strength, 2) lower-body power output, 3) sprint speed and
      jumping ability, 4) anthropometry, and 5) firefighter Grinder performance (i.e.,
      firefighter-specific job tests). The 9-week UT experimental treatment
      prescription was characterized by daily "nonlinear" fluctuations in training to
      preferentially elicit specific and distinct muscular fitness components, whereas
      the STCo treatment conformed to a traditional model, in which each fitness
      component was systematically targeted during a specified mesocycle. For both
      treatments, nearly all fitness and performance measures significantly increased
      from baseline (p < 0.05), with a trend in favor of UT. Further, the UT group
      experienced significantly greater improvements (p < 0.05) in Grinder performance
      over the STCo group. Calculation of effect sizes identified meaningful
      differences in the magnitude of changes in outcomes (effect size > 0.50) in favor
      of UT for measures of thigh circumference, vertical jump, 1RM squat, Grinder
      performance, and peak power output. These findings suggest a potentially greater
      stimulus for multidimensional muscular fitness development with UT, over a
      periodized STCo. This study effectively establishes that UT may offer a greater
      transference to performance for firefighter-specific job tasks.

PMID- 18714215
TI  - Reliability of the reactive strength index and time to stabilization during depth
      jumps.
AB  - The reliability of the reactive strength index (RSI) and time to stabilization
      (TTS) during maximal-effort plyometric depth jumps was examined. Twenty-two
      subjects performed three depth jumps from a height of 30 cm. Measures such as
      height of jump (JH), ground-contact time (CT), RSI, and TTS were obtained and
      analyzed for reliability using Cronbach alpha reliability coefficient and
      intraclass correlations. The JH, CT, and RSI were shown to be highly reliable
      from trial to trial (evidenced by high Cronbach reliability coefficients (alpha >
      0.95) and high single- and average-measures intraclass correlations (>0.9). Time
      to stabilization was not reliable from trial to trial, as evidenced by a low
      Cronbach reliability coefficient (alpha < 0.7) and poor single- (<0.5) and
      average-measures (<0.7) intraclass correlations. The RSI was observed to be
      consistent for single measures, suggesting that coaches dealing with large
      numbers of athletes can conduct only a single trial from each depth jump height
      when attempting to optimize plyometric depth jump heights for their athletes.
      Time to stabilization could be a useful tool for strength and conditioning
      investigators to quantify the landing portion of plyometric exercises, but the
      protocol used in the current study to measure this variable did not prove to be
      reliable. Investigators wishing to use this measurement in such a context in
      future research studies may need to allow subjects appropriate habituation
      periods and control for arm movement during the landing phase of the exercise.

PMID- 18714216
TI  - Effect of breathing pattern on arm coordination symmetry in front crawl.
AB  - This study analyzed the relationship between breathing pattern and arm
      coordination symmetry in 11 expert male swimmers who performed the front crawl at
      their 100-m race pace using seven randomized breathing patterns. Two indexes of
      coordination (IdCP and IdCNP) and a symmetry index (SI) based on the difference
      of IdCP - IdCNP were calculated. IdCP calculated the lag time between the
      beginning of arm propulsion on the nonpreferential breathing side and the end of
      arm propulsion on the preferential breathing side; IdCNP did the converse. The
      IdCP and IdCNP comparisons and the SI showed coordination asymmetries among the
      seven breathing patterns. Specifically, breathing to the preferential side led to
      an asymmetry, in contrast to the other breathing patterns, and the asymmetry was
      even greater when the swimmer breathed to his nonpreferential side. These
      findings highlight the effect of breathing laterality in that coordination was
      symmetric in patterns with breathing that was bilateral, axed (as in breathing
      with a frontal snorkel), or removed (as in apnea). One practical application is
      that arm coordination asymmetry can be prevented or reduced by using breathing
      patterns that balance the coordination.

PMID- 18714217
TI  - Yoga as steadiness training: effects on motor variability in young adults.
AB  - Exercise training programs can increase strength and improve submaximal force
      control, but the effects of yoga as an alternative form of steadiness training
      are not well described. The purpose was to explore the effect of a popular type
      of yoga (Bikram) on strength, steadiness, and balance. Young adults performed
      yoga training (n = 10, 29 +/- 6 years, 24 yoga sessions in 8 weeks) or served as
      controls (n = 11, 26 +/- 7 years). Yoga sessions consisted of 1.5 hours of
      supervised, standardized postures. Measures before and after training included
      maximum voluntary contraction (MVC) force of the elbow flexors (EF) and knee
      extensors (KE), steadiness of isometric EF and KE contractions, steadiness of
      concentric (CON) and eccentric (ECC) KE contractions, and timed balance. The
      standard deviation (SD) and coefficient of variation (CV, SD/mean force) of
      isometric force and the SD of acceleration during CON and ECC contractions were
      measured. After yoga training, MVC force increased 14% for KE (479 +/- 175 to 544
      +/- 187 N, p < 0.05) and was unchanged for the EF muscles (219 +/- 85 to 230 +/-
      72 N, p > 0.05). The CV of force was unchanged for EF (1.68 to 1.73%, p > 0.05)
      but was reduced in the KE muscles similarly for yoga and control groups (2.04 to
      1.55%, p < 0.05). The variability of CON and ECC contractions was unchanged. For
      the yoga group, improvement in KE steadiness was correlated with pretraining
      steadiness (r = -0.62 to -0.84, p < 0.05); subjects with the greatest KE force
      fluctuations before training experienced the greatest reductions with training.
      Percent change in balance time for individual yoga subjects averaged +228% (19.5
      +/- 14 to 34.3 +/- 18 seconds, p < 0.05), with no change in controls. For young
      adults, a short-term yoga program of this type can improve balance substantially,
      produce modest improvements in leg strength, and improve leg muscle control for
      less-steady subjects.

PMID- 18714218
TI  - The acute effects of a caffeine-containing supplement on bench press strength and
      time to running exhaustion.
AB  - The purpose of the present study was to examine the acute effects of a caffeine
      containing supplement (SUPP) on one-repetition maximum (1-RM) bench press
      strength and time to running exhaustion (TRE) at a velocity that corresponded to
      85% of the peak oxygen uptake ([latin capital V with dot above]O2peak). The study
      used a double-blinded, placebo-controlled, crossover design. Thirty-one men (mean
      +/- SD age = 23.0 +/- 2.6 years) were randomly assigned to take either the SUPP
      or placebo (PLAC) first. The SUPP contained 201 mg of caffeine, and the PLAC was
      microcrystalline cellulose. All subjects were tested for 1-RM bench press
      strength and TRE at 45 minutes after taking either the SUPP or PLAC. After 1 week
      of rest, the subjects returned to the laboratory and ingested the opposite
      substance (SUPP or PLAC) from what was taken during the previous visit. The 1-RM
      bench press and TRE tests were then performed in the same manner as before. The
      results indicated that the SUPP had no effect on 1-RM bench press strength or TRE
      at 85% [latin capital V with dot above]O2peak. It is possible that the acute
      effects of caffeine are affected by differences in training status and/or the
      relative intensity of the exercise task. Future studies should examine these
      issues, in addition to testing the acute effects of various caffeine doses on
      performance during maximal strength, power, and aerobic activities. These
      findings do not, however, support the use of caffeine as an ergogenic aid in
      untrained to moderately trained individuals.

PMID- 18714219
TI  - Effects of sodium bicarbonate ingestion on performance and perceptual responses
      in a laboratory-simulated BMX cycling qualification series.
AB  - The objective of this study was to examine the effect of sodium bicarbonate
      (NaHCO3-) ingestion on performance and perceptual responses in a laboratory
      simulated bicycle motocross (BMX) qualification series. Nine elite BMX riders
      volunteered to participate in this study. After familiarization, subjects
      undertook two trials involving repeated sprints (3 x Wingate tests [WTs]
      separated by 30 minutes of recovery; WT1, WT2, WT3). Ninety minutes before each
      trial, subjects ingested either NaHCO3- or placebo in a counterbalanced, randomly
      assigned, double-blind manner. Each trial was separated by 4 days. Performance
      variables of peak power, mean power, time to peak power, and fatigue index were
      calculated for each sprint. Ratings of perceived exertion were obtained after
      each sprint, and ratings of perceived readiness were obtained before each sprint.
      No significant differences were observed in performance variables between
      successive sprints or between trials. For the NaHCO3- trial, peak blood lactate
      during recovery was greater after WT2 (p < 0.05) and tended to be greater after
      WT3 (p = 0.07), and ratings of perceived exertion were not influenced. However,
      improved ratings of perceived readiness were observed before WT2 and WT3 (p <
      0.05). In conclusion, NaHCO3- ingestion had no effect on performance and RPE
      during a series of three WT simulating a BMX qualification series, possibly
      because of the short duration of each effort and the long recovery time used
      between the three WTs. On the contrary, NaHCO3- ingestion improved perceived
      readiness before each WT.

PMID- 18714220
TI  - The immunological and metabolic responses to exercise of varying intensities in
      normoxic and hypoxic environments.
AB  - The purpose of this study was to determine the effects of varying intensities of
      exercise in normoxic and hypoxic environments on selected immune regulation and
      metabolic responses. Using a within-subjects design, subjects performed maximal
      tests on a cycle ergometer in both normoxic (PiO2 = 20.94%) and hypoxic (PiO2 =
      14.65%) environments to determine [latin capital V with dot above]O2max. On
      separate occasions, subjects then performed four randomly assigned, 1-hour
      exercise bouts on a cycle ergometer (two each in normoxic and hypoxic
      environments). The hypoxic environment was created by reducing the O2
      concentration of inspired air using a commercially available hypoxic chamber. The
      intensities for the exercise bouts were predetermined as 40 and 60% of their
      normoxic [latin capital V with dot above]O2max for the normoxic exercise bouts
      and as 40 and 60% of their hypoxic [latin capital V with dot above]O2max for the
      hypoxic exercise bouts. Blood samples were collected preexercise, postexercise,
      15 minutes postexercise, 2 hours postexercise, and 24 hours postexercise for the
      determination of interleukin-1 (IL-1), tumor necrosis factor-[alpha] (TNF
      [alpha]), glucose, glycerol, free fatty acids, epinephrine, norepinephrine, and
      cortisol. There were no significant differences (p < 0.05) between condition or
      intensity for IL-1 or TNF-[alpha]. Significant differences (p < 0.05) between
      intensities were demonstrated for epinephrine, norepinephrine, and cortisol (p <
      0.05). A significant difference was identified between normoxic and hypoxic
      environments with respect to nonesterifed fatty acids (0.45 +/- 0.37 vs. 0.58 +/-
      0.31 mEq x L-1, respectively; p = 0.012). During prolonged exercise at 40 and 60%
      of their respective [latin capital V with dot above]O2max values, hypoxia did not
      seem to dramatically alter the response of the selected immune system or
      metabolic markers. Exercise training that uses acute hypoxic environments does
      not adversely affect immune regulation system status and may be beneficial for
      those individuals looking to increase endurance performance.

PMID- 18714221
TI  - Relationships between repeated sprint testing, speed, and endurance.
AB  - Repeated sprint testing is gaining popularity in team sports, but the methods of
      data analysis and relationships to speed and endurance qualities are not well
      described. We compared three different methods for analyzing repeated sprint test
      results, and we quantified relationships between repeated sprints, short sprints,
      and endurance test scores. Well-trained male junior Australian Football players
      (n = 60, age 18.1 +/- 0.4 years, height 1.88 +/- 0.07 m, mass 82.0 +/- 8.1 kg;
      mean +/- SD) completed a 6 x 30-m repeated sprint running test on a 20-second
      cycle, a 20-m sprint test (short sprint), and the 20-m multistage shuttle run for
      endurance. Repeated sprint results were evaluated in three ways: total time for
      all six sprints (TOTAL), percent change from predicted times (PRED) from the
      fastest 30-m sprint time, and percent change from first to last sprint (CHANGE).
      We observed a very large decrement (CHANGE 6.3 +/- 0.7%, mean +/- 90% confidence
      limits) in 30-m performance from the first to last sprint (4.16 +/- 0.10 to 4.42
      +/- 0.11 seconds, mean +/- SD). Results from TOTAL were highly correlated with 20
      m sprint and 20-m multistage shuttle run tests. Performance decrements calculated
      by PRED were highly correlated with TOTAL (r = 0.91), but neither method was
      directly comparable with CHANGE (r = -0.23 and r = 0.12 respectively). TOTAL was
      moderately correlated with fastest 20-m sprint time (r = 0.66) but not the 20-m
      multistage shuttle run (r = -0.20). Evaluation of repeated sprint testing is
      sensitive to the method of data analysis employed. The total sprint time and
      indices of the relative decrement in performance are not directly
      interchangeable. Repeated sprint ability seems more related to short sprint
      qualities than endurance fitness.

PMID- 18714222
TI  - Effects of combination oral contraceptives on strength development in women
      athletes.
AB  - This study was designed to investigate the effects of combination oral
      contraceptive agents (OCAs) on strength and torque production in collegiate women
      softball and water polo athletes who participated in a 12-week strength
      development program. A double-blind research design was used to mask subjects to
      the main outcome of interest. Thirty-one women collegiate softball and water polo
      players were divided into experimental (OCA users, n = 13), and control (non-OCA
      users, n = 18) groups. All subjects participated in the same supervised 12-week
      preseason strength development program. One-repetition maximum bench press
      (1RMBP), 10-repetition maximum leg extension (10RMLE), isokinetic peak torque
      bench press (IKBP), and isokinetic peak torque leg extension (IKLE) data were
      collected at weeks 0 (pre-test), 4, 8, and 12 (post-test). Significant increases
      in strength and torque production over time were identified regardless of group
      for 1RMBP, 10RMLE, and IKLE. No significant differences in IKBP torque production
      occurred during the 12-week strength training program. No significant differences
      in 1RMBP, 10RMLE, IKBP, or IKLE occurred between the OCA users and the non-OCA
      users groups. It was concluded that, within the limitations of the study, the use
      of combination OCAs did not provide sufficient androgenic effect to increase
      strength gains beyond the stimulus of the training protocol.

PMID- 18714223
TI  - Hormonal responses to resistance exercise in long-term trained and untrained
      middle-aged men.
AB  - This cross-sectional study compared hormonal responses to resistance exercise
      between trained and untrained men to investigate the adaptations of the endocrine
      system to long-term strength training in middle-aged men. Twenty-one middle-aged
      men were recruited for this study and matched into a strength-trained group (SG)
      (n = 10) and an untrained group (UG) (n = 11). In the SG, the individuals had
      practiced strength training for hypertrophy for at least 3 years. Upper- and
      lower-body muscle strength was measured with a 1 repetition maximum (1RM) test.
      Blood samples were collected at rest and after multiple sets of a superset
      strength training protocol (SSTP), with an intensity of 75% of 1RM values. With
      these blood samples, the levels of total testosterone (TT), free testosterone
      (FT), dehydroepiandrosterone (DHEA), cortisol, and sex hormone-binding globulin
      (SHBG) were determined. In addition, the TT-to-cortisol ratio and TT-to-SHBG
      ratio were calculated. There was no difference at rest between groups in hormonal
      values for TT, FT, DHEA, cortisol, the TT-to-SHBG ratio, and the TT-to-cortisol
      ratio. There were increases after SSTP in the levels of TT, FT, DHEA, and
      cortisol and the TT-to-SHBG ratio in the UG, but only FT increased in the SG. The
      SG demonstrated lower values in the TT-to-SHBG ratio after the training session.
      These results suggest the presence of alterations in anabolic and catabolic
      hormonal responses to resistance exercise in long-term trained middle-aged men,
      with the trained subjects demonstrating lower responsiveness in the hormone
      values. Long-term trained men seem to require a higher volume of training, at
      least similar to their daily workout, to stimulate greater hormone responses.

PMID- 18714224
TI  - Pacing pattern and physiological responses to a 5-minute maximal exercise bout.
AB  - The purpose of this study was to describe the pacing strategy of experienced
      cyclists in a 5-minute maximal exercise bout and to describe selected
      physiological responses associated with this effort. Six experienced and well
      trained competitive cyclists (five males, one female) with a mean (+/-SD) age,
      height, and mass of 27.0 +/- 4.77 years, 174.7 +/- 8.57 cm, and 71.0 +/- 6.45 kg,
      performed a 5-minute maximal exercise bout in a laboratory on a racing cycle.
      Subjects were free to determine their work rate throughout. During exercise, data
      were collected for work rate, heart rate (HR), [latin capital V with dot
      above]O2, electromyography of the rectus femoris and vastus lateralis, oxygen
      saturation, and rating of perceived exertion. All six subjects selected a pacing
      strategy characterized by a surge in work rate in the first minute followed by a
      gradual decline until the last minute, when a sprint to the end occurred. Values
      for HR, respiratory exchange ratio, and blood lactate concentration (182.8 +/-
      2.8 bpm, 1.08 +/- 0.07, and 15.5 +/- 2.1 mmol x L-1, respectively) indicated that
      [latin capital V with dot above]O2 (3.6 +/- 0.4 L x min-1) was close to or at
      maximum from minutes 2 to 5. Oxygen saturation dropped continuously across time,
      reaching <94% in the last minute, and rating of perceived exertion was 19.5 +/-
      0.8. Electromyographic activity of the rectus femoris and vastus lateralis was
      not significantly related to work rate during the bout (p > 0.05). It is
      concluded that work rate or pace is uneven in an all-out, 5-minute exercise bout
      in experienced cyclists, yet the physiological responses are near maximal in
      minutes 2-5. Cyclists seem to pace themselves in a common pattern in short-term
      stochastic exercise bouts. The possible benefits of including some stochastic
      exercise in the training programs of athletes might be worthy of examination.

PMID- 18714225
TI  - Resting energy expenditure and delayed-onset muscle soreness after full-body
      resistance training with an eccentric concentration.
AB  - The purpose of this investigation was to determine the effect of an acute bout of
      high-volume, full-body resistance training with an eccentric concentration on
      resting energy expenditure (REE) and indicators of delayed-onset muscle soreness
      (DOMS). Eight resistance trained (RT) and eight untrained (UT) participants
      (mean: age = 23.5 years; height = 180.76 cm; weight = 87.58 kg; body fat =
      19.34%; lean mass = 68.71 kg) were measured on four consecutive mornings for REE
      and indicators of DOMS: creatine kinase (CK) and rating of perceived muscle
      soreness (RPMS). Delayed-onset muscle soreness was induced by performing eight
      exercises, eight sets, and six repetitions using a 1-second concentric and 3
      second eccentric muscle action duration. A two-factor repeated-measures analysis
      of variance revealed that REE was significantly (p < 0.05) elevated at 24, 48,
      and 72 hours post compared with baseline measures for both UT and RT groups.
      Ratings of perceived muscle soreness were significantly elevated within groups
      for UT and RT at 24 and 48 hours post and for UT only at 72 hours post compared
      with baseline (p < 0.05). Nonparametric analyses revealed that CK was
      significantly increased at 24 hours post for both UT and RT and at 48 and 72
      hours post for UT only compared with baseline (p < 0.05). Resting energy
      expenditure and indicators of DOMS were higher in UT compared with RT on all
      measures, but no significant differences were determined. The main finding of
      this investigation is that full-body resistance training with an eccentric
      concentration significantly increased REE up to 72 hours postexercise in UT and
      RT participants.

PMID- 18714226
TI  - The reliability and validity of fatigue measures during multiple-sprint work: an
      issue revisited.
AB  - The ability to repeatedly produce a high-power output or sprint speed is a key
      fitness component of most field and court sports. The aim of this study was to
      evaluate the validity and reliability of eight different approaches to quantify
      this parameter in tests of multiple-sprint performance. Ten physically active men
      completed two trials of each of two multiple-sprint running protocols with
      contrasting recovery periods. Protocol 1 consisted of 12 x 30-m sprints repeated
      every 35 seconds; protocol 2 consisted of 12 x 30-m sprints repeated every 65
      seconds. All testing was performed in an indoor sports facility, and sprint times
      were recorded using twin-beam photocells. All but one of the formulae showed good
      construct validity, as evidenced by similar within-protocol fatigue scores.
      However, the assumptions on which many of the formulae were based, combined with
      poor or inconsistent test-retest reliability (coefficient of variation range: 0.8
      145.7%; intraclass correlation coefficient range: 0.09-0.75), suggested many
      problems regarding logical validity. In line with previous research, the results
      support the percentage decrement calculation as the most valid and reliable
      method of quantifying fatigue in tests of multiple-sprint performance.

PMID- 18714227
TI  - Relationship between the kinetics and kinematics of a unilateral horizontal drop
      jump to sprint performance.
AB  - The aim of this study was to investigate the relationship between the kinematics
      and kinetics of a single-leg horizontal drop jump (SLDJ) to sprint performance.
      Twenty regional-level male team-sport athletes gave informed consent to
      participate in this study. All subjects performed a series of 25-m sprints
      (measured by dual-beam infrared timing lights) and SLDJ (with both legs) in
      randomized block order during the same testing session. The SLDJ required the
      subjects to step downwards off a 20-cm box, land on the force plate (operating at
      500 Hz) with the specified foot, and jump for maximal horizontal distance while
      minimizing ground-contact time. Jump distance, particularly when normalized to a
      subject's height, was the strongest correlate to sprinting time for all three (5,
      10, and 25 m) distances (-0.44 < r < -0.65). Multiple linear regression analyses
      indicated that the SLDJ could account for a high level of variance in sprint time
      (0.49 < r2 < 0.68) and that these predictions had a relatively low standard error
      of estimate (0.02-0.10 seconds). These results further support the contention
      that jump (particularly horizontal) and sprint ability for short distances are
      highly related. Whereas practitioners should consider using more horizontal than
      vertical jumps in the training and testing of most team-sport athletes,
      additional research into the kinetic determinants of jumping and sprinting may
      allow a more specific and individualized exercise prescription for improving
      certain aspects of sprinting such as step length or step rate or the vertical vs.
      horizontal contributions to propulsion.

PMID- 18714228
TI  - Muscular outputs during dynamic bench press under stable versus unstable
      conditions.
AB  - Previous studies have suggested that resistance training exercise under unstable
      conditions decreases the isometric force output, yet little is known about its
      influence on muscular outputs during dynamic movement. The objective of this
      study was to investigate the effect of an unstable condition on power, force, and
      velocity outputs during the bench press. Twenty male collegiate athletes (mean
      age, 21.3 +/- 1.5 years; mean height, 167.7 +/- 7.7 cm; mean weight, 75.9 +/-
      17.5 kg) participated in this study. Each subject attempted 3 sets of single
      bench presses with 50% of 1 repetition maximum (1RM) under a stable condition
      with a flat bench and an unstable condition with a Swiss ball. Acceleration data
      were obtained with an accelerometer attached to the center of a barbell shaft,
      and peak outputs of power, force, and velocity were computed. Although
      significant loss of the peak outputs was found under the unstable condition (p <
      0.017), their reduction rates remained relatively low, approximately 6% for force
      and 10% for power and velocity outputs, compared with previous findings. Such
      small reduction rates of muscular outputs may not compromise the training effect.
      Prospective studies are necessary to confirm whether the resistance training
      under an unstable condition permits the improvement of dynamic performance and
      trunk stability.

PMID- 18714229
TI  - Validity and reliability of a new stair sprinting test of explosive power.
AB  - The purpose of this study was to examine the validity and reliability of a new
      stair sprinting power (SSP) test and, in addition, develop norms for college-age
      students. Two hundred twenty-seven college-age volunteers participated in the
      study (ages: males, [Latin capital letter X with macron above] = 21.6 +/- 2.264
      years; females, [Latin capital letter X with macron above] = 22.3 +/- 4.214
      years). The majority (n = 192) were tested with stopwatches, and 35 were tested
      using Speedtrap II. Participants began with their back to a wall 1.87 m from the
      first step of a 2.04-m high staircase of which they sprinted 2 steps per stride
      to the top. Scores were explosive power = (body mass (kg) x 98 x 2.04)/time (s).
      Excellent test-retest reliability (intraclass R) was demonstrated: overall, F(1,
      226) = 0.420, p = 0.518, R = 0.986; stopwatch: males, F(1, 118) = 0.045, p =
      0.833, R = 0.970; and females, F(1, 72) = 0.000, p = 0.998, R = 0.977; and the
      Speedtrap II: males, F(1, 15) = 2.599, p = 0.128, R = 0.982; and females, F(1,
      18) = 0.010, p = 0.921, R = 0.980. In addition, vertical jumping distance (VJD)
      was acquired on 25 of the Speedtrap II participants. Using Pearson product moment
      correlation, relationships were determined between SSP, vertical jumping distance
      (VJD), and vertical jumping power (VJP): VJP = (W) = 51.9 x countermovement VJD
      (cm) + 48.9 x body mass (kg) - 2007. Overall, the correlation between SSP and VJD
      was strong, r = 0.692, p = 0.000; however, correlations by sex were neither
      significant nor meaningful. Significantly strong correlations were found between
      SSP and VJP: overall, r = 0.943, p = 0.000; males, r = 0.903, p = 0.000; and
      females, r = 0.835, p = 0.000. It was concluded that the new test was safe,
      quick, easy to administer, inexpensive, reliable, and valid both logically and
      concurrently when used with college-age males and females.

PMID- 18714230
TI  - Accuracy of prediction equations for determining one repetition maximum bench
      press in women before and after resistance training.
AB  - Repetitions to fatigue (RTF) using less than a 1 repetition maximum (1RM) load
      (RepWt) have been shown to be a good predictor of 1RM strength in men, but such
      information is scarce in women. The purpose of this study was to evaluate the
      accuracy of current prediction equations to estimate 1RM bench press performance
      and to determine whether resistance training changes the capability to predict
      1RM from muscular endurance repetitions in young women. Members (n = 103) of a
      required wellness course were measured for 1RM bench press and RTF using randomly
      assigned percentages between 60% and 90% of the 1RM (RepWt) before and after 12
      weeks of progressive resistance training. The %1RM used to perform RTF remained
      the same for each individual after training (75.6% +/- 10.3%) as before. One
      repetition maximum bench press increased significantly after training (28% +/-
      21%). Although the change in the group average for RTF (0.6 +/- 6.1) was not
      significant, the correlation between pretraining and posttraining RTF was
      moderate (r = 0.66; p < 0.01), and individual differences in percentage change in
      RTF were substantial (27% +/- 99%). The percentage change in 1RM was not
      significantly related to initial 1RM (r = -0.05), but it was negatively related
      to the change in RTF (r = -0.40; p < 0.01). Prediction equations were more
      accurate in the pretraining and posttraining conditions, in which fewer than 10
      RTF were used. Resistance training may alter the relationship between strength
      and muscle endurance across a wide range of RTF in young women without
      compromising the accuracy of predicting maximal strength.

PMID- 18714231
TI  - Influence of pelvis position on the activation of abdominal and hip flexor
      muscles.
AB  - A pelvic position has been sought that optimizes abdominal muscle activation
      while diminishing hip flexor activation. Thus, the objective of the study was to
      investigate the effect of pelvic position and the Janda sit-up on trunk muscle
      activation. Sixteen male volunteers underwent electromyographic (EMG) testing of
      their abdominal and hip flexor muscles during a supine isometric double straight
      leg lift (DSLL) with the feet held approximately 5 cm above a board. The second
      exercise (Janda sit-up) was a sit-up action where participants simultaneously
      contracted the hamstrings and the abdominal musculature while holding an
      approximately 45 degrees angle at the knee. Root mean square surface
      electromyography was calculated for the Janda sit-up and DSLL under 3 pelvic
      positions: anterior, neutral, and posterior pelvic tilt. The selected muscles
      were the upper and lower rectus abdominis (URA, LRA), external obliques, lower
      abdominal stabilizers (LAS), rectus femoris, and biceps femoris. The Janda sit-up
      position demonstrated the highest URA and LRA activation and the lowest rectus
      femoris activation. The Janda sit-up and the posterior tilt were significantly
      greater (p < 0.01 and p < 0.05, respectively) than the anterior tilt for the URA
      and LRA muscles. Activation levels of the URA and LRA in neutral pelvis were
      significantly (p < 0.01 and p < 0.05, respectively) less than the Janda sit-up
      position, but not significantly different from the posterior tilt. No significant
      differences in EMG activity were found for the external obliques or LAS. No
      rectus femoris differences were found in the 3 pelvis positions. The results of
      this study indicate that pelvic position had a significant effect on the
      activation of selected trunk and hip muscles during isometric exercise, and the
      activation of the biceps femoris during the Janda sit-up reduced the activation
      of the rectus femoris while producing high levels of activation of the URA and
      LRA.

PMID- 18714232
TI  - Validity of a total body recumbent stepper exercise test to assess
      cardiorespiratory fitness.
AB  - Maximum oxygen consumption ([latin capital V with dot above]o2max) is the primary
      measure for cardiorespiratory fitness, and the [latin capital V with dot
      above]o2max value achieved on the treadmill using the Bruce protocol is
      considered the gold standard. A novel exercise test using a total body recumbent
      stepper (TBRS) would be an alternative for measuring [latin capital V with dot
      above]o2max in healthy individuals. Furthermore, the TBRS exercise test (TBRS-XT)
      may be beneficial for individuals such as those with stroke, who cannot tolerate
      a treadmill or cycle ergometer test due to hemiparesis, increased tone in the
      extremities, or balance deficits. The purpose of the study was to assess the
      validity and reliability of the TBRS-XT in determining [latin capital V with dot
      above]o2max in healthy adults. Twenty-two healthy adults (9 women, 13 men; 26.9
      +/- 6.1 years of age) participated in 2 maximum exercise tests in random order.
      One exercise test was performed on the treadmill using the Bruce protocol and the
      other exercise test was the TBRS-XT. Statistical analysis of the data was
      conducted using simple linear regression where the response variable was the
      [latin capital V with dot above]o2max from the Bruce protocol and the predictor
      variable was the [latin capital V with dot above]o2max from the TBRS-XT. A 95%
      prediction interval was used to assess the strength of the prediction of [latin
      capital V with dot above]o2 from the Bruce protocol with R2 = 0.851. Preliminary
      data suggest that the TBRS-XT may be a valid test to predict [latin capital V
      with dot above]o2max when treadmill testing is not feasible. This would allow
      clinicians an alternative method for exercise testing and prescription to promote
      healthy lifestyle interventions for a variety of patient populations.

PMID- 18714233
TI  - Force-generating capacities and fatigability of the quadriceps femoris in
      relation to different exercise modes.
AB  - In this study, we examined whether different exercise modes provoke functional
      differences in maximal and explosive force-generating capacities and fatigability
      of the quadriceps femoris (QF). Additionally, the interaction of different
      functional capacities was studied in competitive athletes. Ten competitive tennis
      players and 10 endurance athletes participated in the study. Pre-exercise force
      generating capacities were determined during maximal voluntary isometric knee
      extensions (MVC). Fatigability of the QF was studied using sustained isometric
      contractions with target loads of 20% and 40% of pre-exercise MVC. Postexercise
      MVCs were conducted 20 seconds, 1 minute, and 3 minutes post task failure. Muscle
      activation of the QF during the fatiguing exercises and postexercise MVCs was
      estimated using surface electromyography. Higher explosive force-generating
      capacities, but no differences in absolute moments, were detected in tennis
      players compared with endurance athletes. Fatigability of the QF during both
      fatiguing tasks was approximately the same in both athletic populations. This was
      indicated by minor group differences in endurance time, postexercise MVC
      production, and electromyography (EMG)-estimated muscle activation during
      fatigue. Variability in endurance time was not significantly associated with pre
      exercise force-generating capacities in these competitive athletes. In both
      athletic populations, recovery of MVC was significantly slower after the
      fatiguing contraction with 20% of MVC compared with that with 40% of MVC. These
      results may enhance understanding of plasticity of the neuromuscular system and
      yield interesting information for the optimization of athletic training programs.
      Explosive strength training might enhance endurance athletes' explosiveness
      without decreasing muscle fatigue resistance. The exercise profile of competitive
      tennis is suggested to act as a sufficient trigger to reach high neuromuscular
      fatigue resistance but may be inadequate to cause significant gains in absolute
      muscle strength.

PMID- 18714234
TI  - Relationship of physical fitness test results and hockey playing potential in
      elite-level ice hockey players.
AB  - The primary purpose of this study was to determine the fitness variables with the
      highest capability for predicting hockey playing potential at the elite level as
      determined by entry draft selection order. We also examined the differences
      associated with the predictive abilities of the test components among playing
      positions. The secondary purpose of this study was to update the physiological
      profile of contemporary hockey players including positional differences. Fitness
      test results conducted by our laboratory at the National Hockey League Entry
      Draft combine were compared with draft selection order on a total of 853 players.
      Regression models revealed peak anaerobic power output to be important for higher
      draft round selection in all positions; however, the degree of importance of this
      measurement varied with playing position. The body index, which is a composite
      score of height, lean mass, and muscular development, was similarly important in
      all models, with differing influence by position. Removal of the goalies' data
      increased predictive capacity, suggesting that talent identification using
      physical fitness testing of this sort may be more appropriate for skating
      players. Standing long jump was identified as a significant predictor variable
      for forwards and defense and could be a useful surrogate for assessing overall
      hockey potential. Significant differences exist between the physiological
      profiles of current players based on playing position. There are also positional
      differences in the relative importance of anthropometric and fitness measures of
      off-ice hockey tests in relation to draft order. Physical fitness measures and
      anthropometric data are valuable in helping predict hockey playing potential.
      Emphasis on anthropometry should be used when comparing elite-level forwards,
      whereas peak anaerobic power and fatigue rate are more useful for differentiating
      between defense.

PMID- 18714235
TI  - Acute effects of static, dynamic, and proprioceptive neuromuscular facilitation
      stretching on muscle power in women.
AB  - The purpose of this study was to investigate the acute effects of 3 types of
      stretching-static, dynamic, and proprioceptive neuromuscular facilitation (PNF)
      on peak muscle power output in women. Concentric knee extension power was
      measured isokinetically at 60 degrees x s(-1) and 180 degrees x s(-1) in 12
      healthy and recreationally active women (mean age +/- SD, 24 +/- 3.3 years).
      Testing occurred before and after each of 3 different stretching protocols and a
      control condition in which no stretching was performed. During 4 separate
      laboratory visits, each subject performed 5 minutes of stationary cycling at 50 W
      before performing the control condition, static stretching protocol, dynamic
      stretching protocol, or PNF protocol. Three submaximal warm-up trials preceded 3
      maximal knee extensions at each testing velocity. A 2-minute rest was allowed
      between testing at each velocity. The results of the statistical analysis
      indicated that none of the stretching protocols caused a decrease in knee
      extension power. Dynamic stretching produced percentage increases (8.9% at 60
      degrees x s(-1) and 6.3% at 180 degrees x s(-1)) in peak knee extension power at
      both testing velocities that were greater than changes in power after static and
      PNF stretching. The findings suggest that dynamic stretching may increase acute
      muscular power to a greater degree than static and PNF stretching. These findings
      may have important implications for athletes who participate in events that rely
      on a high level of muscular power.

PMID- 18714236
TI  - Effect of Olympic and traditional resistance training on vertical jump
      improvement in high school boys.
AB  - The purpose of this study was to compare the effects of a ballistic resistance
      training program of Olympic lifts with those of a traditional resistance training
      program of power lifts on vertical jump improvement in male high school athletes.
      Twenty-seven male student athletes were recruited from a high school football
      program at a small, rural school in the Southeast. The subjects were divided into
      an Olympic training group (OT, n = 11), a power training group (PT, n = 10), and
      a control group (n = 6). Analysis of variance was used to determine whether a
      significant mean difference existed among groups on vertical jump improvement
      after 8 weeks of group-specific training. Effect size of vertical jump
      improvement between groups, and correlations between strength and vertical jump
      performance, were also examined. There was no significant mean difference (p >or=
      0.05) among OT, PT, and control groups, but large effect sizes between OT and
      control (d = 1.06) and PT and control (d = 0.94) demonstrate that both OT and PT
      are effective in improving vertical jump performance in male high school
      athletes. Moderate to high correlations were noted between squat score and
      vertical jump after adjusting for body weight (r = 0.42) and between power clean
      and vertical jump after adjusting for body weight (r = 0.75). Findings from the
      current study indicate that Olympic lifts as well as power lifts provide
      improvement in vertical jump performance and that Olympic lifts may provide a
      modest advantage over power lifts for vertical jump improvement in high school
      athletes.

PMID- 18714237
TI  - Determinants of physical activity among a convenience sample of Puerto Rican
      women residing in the Northeastern United States.
AB  - The research examining determinants of physical activity among Hispanics focuses
      on Mexican Americans, although Puerto Ricans are the second largest Hispanic
      subgroup in the United States. The purpose of this study was to explore factors
      influencing physical activity among Puerto Rican women in the urban northeastern
      United States. Two bilingual female investigators administered the Women and
      Physical Activity Survey by telephone to a convenience sample of Puerto Rican
      women (n = 28). Women were categorized as physically active if they performed
      moderate-intensity physical activity for at least 30 minutes a day at least 5
      days a week or vigorous-intensity physical activity for at least 20 minutes a day
      at least 3 days a week. Women not meeting these criteria were classified as
      physically inactive. Chi-squared testing revealed whether the physically active
      and inactive women differed among physical activity determinants. Respondents had
      a mean age of 36 years and were predominately college-educated (64%) and
      physically active (68%). More physically active women (90%) had an annual income
      of more than $35,000 than did the inactive women (10%) (p < 0.05). More
      physically active women belonged to community groups (42% versus 0%), lived in
      communities where people exercise (95% versus 11%), and felt their community was
      good for their family (100% versus 67%) than did the inactive women, respectively
      (p < 0.05). The physically active women reported the presence of exercise
      facilities (p = 0.084) and well-maintained sidewalks (p = 0.087) to be more
      important for exercise accessibility than did the inactive women. Annual income,
      sense of community, and exercise accessibility were the most important physical
      activity determinants in this convenience sample of Puerto Rican women. Factors
      influencing the physical activity levels of Puerto Rican women should continue to
      be explored so that targeted, culturally appropriate strategies can be developed
      to promote physically activity in this population.

PMID- 18714238
TI  - Concurrent training enhances athletes' cardiovascular and cardiorespiratory
      measures.
AB  - We evaluated the effects of concurrent strength and aerobic endurance training on
      cardiovascular and cardiorespiratory adaptations in college athletes and compared
      two concurrent exercise (CE) protocols. Separate experiments were performed on 30
      women (mean age 19.6 years) and 20 men (20.4 years). In both experiments,
      subjects were divided into two groups (serial CE and integrated CE) matched for
      initial physical condition and trained in a vigorous 3-day per week CE program of
      9 (men) to 11 (women) weeks. The two CE training protocols were equilibrated for
      exercise mode, intensity, and volume, differing only in the timing and sequence
      of exercises. During training, serial CE discernibly (p < 0.05) increased
      cardiovascular adaptation in women, indicated by reduction (-5.7%) in active
      heart rate (HR) (HR/aerobic exercise intensity), whereas integrated CE
      discernibly reduced active HR in women (-10.7%) and men (-9.1%). Before and after
      comparisons in the larger sample of women showed that serial CE discernibly
      reduced systolic and diastolic blood pressure (BP) (-8.7% and -14.0%,
      respectively), increased estimated [latin capital V with dot above]o2max (18.9%),
      and produced a trend (0.10 > p > 0.05) toward reduced resting HR (-4.9%).
      Integrated CE in women discernibly reduced systolic and diastolic BP (-13.2% and 
      12.6%, respectively), increased estimated [latin capital V with dot above]o2max
      (22.9%), and produced a trend toward reduced resting HR (-2.4%). Integrated CE
      produced discernibly larger gains than serial CE or a trend for four of six
      training adaptations. Effect sizes were generally large (60.0% of discernible
      differences). We conclude that, for cardiovascular and cardiorespiratory
      adaptations in athletes, strength and endurance training are compatible and that
      exercise timing and sequence significantly influence training adaptations,
      complimenting our previous similar conclusions for strength, muscle endurance,
      body composition, and flexibility.

PMID- 18714239
TI  - Concurrent training enhances athletes' strength, muscle endurance, and other
      measures.
AB  - We evaluated the effects of concurrent strength and aerobic endurance training on
      muscle strength and endurance, body composition, and flexibility in female
      college athletes and compared two concurrent exercise (CE) protocols. Twenty
      eight women (mean age, 19.6 years) were divided into two matched groups and
      evaluated before and after a vigorous, 11-week, 3-days per week CE training
      program. One group did serial CE consisting of a warm-up, resistance exercises at
      low heart rate (HR), aerobics, and a range of motion cool down. The other group
      did integrated CE consisting of aerobics, the same resistance exercises at high
      HR achieved by cardioacceleration before each set, and the same range of motion
      cool down. The two protocols were balanced, differing only in the timing and
      sequence of exercises. Serial CE produced discernible (p < 0.05) increases in
      lower- (17.2%) and upper- (19.0%) body muscle strength and fat-free mass (FFM)
      (1.8%) and trends toward greater lower-body muscle endurance (18.2%) and reduced
      upper-body flexibility (-160.4%). Integrated CE produced discernible increases in
      lower- (23.3%) and upper- (17.8%) body muscle strength, lower-body muscle
      endurance (27.8%), FFM (3.3%), and lower-body flexibility (8.4%) and a decline in
      fat mass (-4.5%) and percent body fat (-5.7%). Integrated CE produced discernibly
      larger gains than serial CE for six of nine training adaptations. Effect sizes
      were generally moderate (44.4% of discernible differences) to large (33.3%). We
      conclude that serial CE produces adaptations greater than those reported in the
      literature for single-mode (strength) training in athletes, whereas integrated CE
      produces discernibly greater gains than serial CE. The results suggest synergy
      rather than interference between concurrent strength and aerobic endurance
      training, support prescription of CE under defined conditions, establish the
      importance of exercise timing and sequence for CE program outcomes, and document
      a highly effective athletic training protocol.

PMID- 18714240
TI  - Evaluating sprinting ability, density of acceleration, and speed dribbling
      ability of professional soccer players with respect to their positions.
AB  - The aim of this study is to evaluate sprinting ability, density of acceleration,
      and speed dribbling ability of professional soccer players with respect to their
      positions.A total of 243 professional soccer players were examined. These soccer
      players are playing in different leagues of Turkey. The F-MARC test battery,
      which was designed by FIFA, was used for soccer players. We did not find any
      statistical differences for 30-m sprint test and four-line sprint test values
      with respect to positions of soccer players (p > 0.05). On the other hand, there
      was a statistical difference for speed dribbling test values in terms of
      positions of soccer players (p < 0.05). It was found that the test values of
      defense players, midfielders, and forwards were better than the test values of
      goalkeepers (p < 0.05). In conclusion, this study, which was done during the
      training season, shows that there is a similarity between the abilities of
      professional soccer players for 30-m sprint and four-line sprint tests.
      Therefore, it is believed that there must be fast players in all positions in
      terms of sprint ability. There is a similarity among defenders, midfielders, and
      forwards in terms of speed dribbling ability; in contrast, the speed dribbling
      ability of goal keepers is different from the players in those three positions.
      Although there are many more speed dribbling exercises within the training
      programs of defenders, midfielders, and forwards, the speed dribbling ability
      test is not used much for goal keepers. Correspondingly, speed dribbling ability
      is not a specific indicator for goal keepers, and this test should not be used
      for the choice of goalkeepers.

PMID- 18714241
TI  - Contributions of body fat and effort in the 5K run: age and body weight handicap.
AB  - The 5K handicap (5KH), designed to eliminate the body weight (BW) and age biases
      inherent in the 5K run time (RT), yields an adjusted RT (RTadj) that can be
      compared between runners of different BW and age. As hypothesized in a validation
      study, however, not all BW bias may be removed, because of the influences of body
      fatness (BF) and effort (run speed; essentially the inverse as measured by rating
      of perceived exertion (RPE)). This study's purpose was to determine the effects
      of BF and RPE on BW bias in the 5KH. For 99 male runners in a regional 5K race
      (age = 43.9 +/- 12.1 years; BW = 83.4 +/- 12.9 kg), BF was determined via sum of
      three skinfolds just before the race. RPE, on the 20-point Borg scale, was used
      to assess overall race effort on race completion. Multiple regression analysis
      was used to develop a new adjusted RT (NRTadj, the RTadj corrected for BF and
      RPE), which was computed for each runner and then correlated with BW to determine
      bias. Indicative of slight bias, BW was correlated with RTadj (r = 0.220, p =
      0.029). Both BF (p = 0.00002) and RPE (p = 0.0005) were significant, independent
      predictors of RTadj. NRTadj was not significantly correlated with BW (r = 0.051,
      p = 0.61), but BF explained 90%, and RPE explained only 6%, of the remaining BW
      bias evidenced in the 5KH. The previous finding that the 5KH does not remove all
      BW bias is apparently accounted for by BF and not RPE. Because no handicap should
      be awarded for higher BF, this finding suggests that the 5KH, for men,
      appropriately adjusts for the age and BW vs. RT biases previously noted.

PMID- 18714242
TI  - Trekking poles increase physiological responses to hiking without increased
      perceived exertion.
AB  - Trekking poles are used by hikers for improved stability and lowered leg fatigue
      due to increased upper body muscle involvement. However, the weight of the poles
      and exaggerated upper body movement when using poles may increase total energy
      expenditure at a given walking speed. Few studies have investigated the
      physiological responses of hiking with trekking poles outside the laboratory
      setting. The purposes of this study were to determine if trekking poles altered
      physiological responses to hiking on varied terrain, and whether responses
      between trials were dependent on the grade of the terrain. Fourteen recreational
      hikers completed four hiking trials over a course that included sustained
      sections of flat (0 +/- 1% grade), steep uphill (>10% grade), gradual uphill (5%
      grade), gradual downhill (-5% grade) and steep downhill (<-10% grade) terrain.
      Subjects walked at a self-selected speed that was matched across trials using
      time-splits and a metronome. Two trials were conducted with hiking poles and two
      without poles. [latin capital V with dot above]O2 was significantly elevated (p
      <0.05) during the pole trials (1502.9 +/- 510.7 ml/min) compared to the no-pole
      trials (1362.4 +/- 473.2 ml/min). Similarly, ventilatory efficiency ([latin
      capital V with dot above]E) (43.1 +/- 9.6; 38.3 +/- 10.1 L/min) and heart rate
      (HR) (112.1 +/- 9.7; 105.7 +/- 10.4 bt/min) were significantly higher during the
      pole trials than the no-pole trials. However, ratings of perceived exertion (RPE)
      was not altered by pole condition (8.5 +/- 0.7; 8.4 +/- 0.8). Comparisons within
      each grade revealed significantly higher physiological responses for [latin
      capital V with dot above]O2, [latin capital V with dot above]E and HR in the pole
      condition at all grades, with no significant variable*grade interactions. RPE
      measures were not significantly different between pole trials at any grade. These
      data suggest that trekking poles may be a beneficial tool for increasing caloric
      expenditure, as energy production increased during exercise without increased
      perceptions of effort.

PMID- 18714243
TI  - Study of the fatigue curve in quadriceps and hamstrings of soccer players during
      isokinetic endurance testing.
AB  - Many studies have presented regression models of quadriceps (Q) muscle strength
      loss with fatigue development. Paradoxically, the hamstrings (H), which are the
      principal site of muscle injury in soccer players, have received little
      attention, and no regression model has been established. This study investigated
      strength loss in the Q and H to establish a regression model using the lowest
      number of flexions-extensions during isokinetic endurance testing. Twenty-four
      semiprofessional soccer players performed 50 flexion-extension movements at 180
      degrees x s(-1) on an isokinetic dynamometer. The theoretical equations were
      calculated from the first 10, first 15, first 20, and first 25 contractions for
      each muscle group by several regression models (linear, quadratic, cubic). The
      linear model was the best fit to this exercise protocol to describe the strength
      loss in both muscle groups. The quadratic model was the best fit to predict the
      changes in the H/Q ratio. This study showed that a regression model can be
      established for both muscle groups. A minimum of 20 extensions and 15 flexions
      was needed to establish a linear model that represented strength loss in,
      respectively, Q and H. A minimum of 25 flexions-extensions was needed with the
      quadratic model to accurately determine the decrease in the H/Q ratio. Isokinetic
      endurance testing can be carried out with only 25 flexions-extensions. This
      reduction should facilitate the implementation of this protocol. Regular
      evaluation would contribute to the efforts to prevent muscle injury during
      competitive sports activity.

PMID- 18714244
TI  - Heart rate responses during small-sided games and short intermittent running
      training in elite soccer players: a comparative study.
AB  - The purpose of this study was to compare heart rate (HR) responses within and
      between physical controlled (short-duration intermittent running) and physical
      integrated (sided games) training methods in elite soccer players. Ten adult male
      elite soccer players (age, 26 +/- 2.9 years; body mass, 78.3 +/- 4.4 kg; maximum
      HR [HRmax], 195.4 +/- 4.9 b x min(-1) and velocity at maximal aerobic speed
      (MAS), 17.1 +/- 0.8 km x h(-1)) performed different short-duration intermittent
      runs, e.g., 30-30 (30 seconds of exercise interspersed with 30 seconds of
      recovery) with active recovery, and 30-30, 15-15, 10-10, and 5-20 seconds with
      passive recovery, and different sided games (1 versus 1, 2 versus 2, 4 versus 4,
      8 versus 8 with and without a goalkeeper, and 10 versus 10). In both training
      methods, HR was measured and expressed as a mean percentage of HR reserve
      (%HRres). The %HRres in the 30-30-second intermittent run at 100% MAS with active
      recovery (at 9 km.h with corresponding distance) was significantly higher than
      that with passive recovery (85.7% versus 77.2% HRres, respectively, p < 0.001)
      but also higher than the 1 versus 1 (p < 0.01), 4 versus 4 (p <or= 0.05), 8
      versus 8 (p < 0.001), and 10 versus 10 (p < 0.01) small-sided games. The %HRres
      was 2-fold less homogeneous during the different small-sided games than during
      the short-duration intermittent running (intersubjects coefficient of variation
      [CV] = 11.8% versus 5.9%, respectively). During the 8 versus 8 sided game, the
      presence of goalkeepers induced an approximately 11% increase in %HRres and
      reduced homogeneity when compared to games without goalkeepers (intersubject CV =
      15.6% versus 8.8%). In conclusion, these findings showed that some small-sided
      games allow the HR to increase to the same level as that in short-duration
      intermittent running. The sided game method can be used to bring more variety
      during training, mixing physical, technical, and tactical training approaching
      the intensity of short-duration intermittent running but with higher intersubject
      variability.

PMID- 18714245
TI  - Effects of a short-term resistance program using elastic bands versus weight
      machines for sedentary middle-aged women.
AB  - This study was designed to determine whether different effects on functional
      capacity and body composition were produced by using different devices (elastic
      bands (EBs) versus weight machines (WMs)) with the same resistance training
      program. Forty-five healthy sedentary middle-aged women volunteers were chosen
      and randomly assigned to 1 of 3 groups: 21 subjects trained using EBs (EBG), 14
      in trained using WMs (WMG), and 10 were controls (CG). Both exercise groups
      trained with a periodized muscular endurance program twice a week for 10 weeks,
      with a total of 6 exercises per session for the major muscle groups. Exercise
      intensity was equalized by jointly monitoring the same targeted number of
      repetitions (TNRs) and rate of perceived exertion in active muscles (RPE-AM).
      Functional capacity was assessed by using knee push-up (KPU) and 60-second squat
      (S) tests. Body composition was measured using an 8-polar bioelectrical impedance
      analyzer. The results for both the EBG and WMG show a decrease in fat mass (p =
      0.05 and p < 0.01, respectively) and an increase in both the fat-free mass (p <
      0.05 and p < 0.01, respectively) and the number of repetitions in the KPU (p <
      0.05 and p < 0.01, respectively) and S tests (p < 0.01 in both). None of the
      variables measured for the CG varied significantly. It can be concluded that,
      independently of the device used, the combined monitoring of TNRs and RPE-AM can
      be a valid tool for controlling the resistance exercise intensity and can lead to
      healthy adaptations. EBs can thus offer significant physiological benefits that
      are comparable to those obtained from WMs in the early phase of strength training
      of sedentary middle-aged women.

PMID- 18714247
TI  - Unilateral balance performance in female collegiate soccer athletes.
AB  - The Star Excursion Balance Test (SEBT) is a unilateral balance task designed to
      evaluate dynamic postural control. This investigation explored the relationship
      between limb preference, strength, and performance on the SEBT in NCAA Division
      I, female collegiate soccer athletes (nonsoccer, n = 11; soccer, n = 12). Each
      participant completed maximal, concentric test efforts at a velocity of 90
      degrees x s(-1) for supine ankle dorsiflexion (ADF) and plantarflexion (APF) and
      at 60 degrees x s(-1) for the seated leg extension (LE) and flexion (LF) and
      supine hip extension (HE) and flexion (HF). In addition, participants performed
      maximal SEBT reaches in the anterior, medial, and posterior directions. All
      testing was completed on both limbs. These results indicate that SEBT performance
      is similar for both limbs in both groups. The soccer group, however, reached
      significantly farther than the nonsoccer group, suggesting that the SEBT may be
      sensitive to training status and/or sport-related adaptations. The concentric
      strength results indicate that despite group differences in all strength tests,
      strength in general was not highly correlated to SEBT performance. Thus,
      neuromuscular factors above and beyond strength may have accounted for the group
      differences in SEBT performance. The SEBT may be a useful tool for determining
      the relative effectiveness of an intervention designed to improve postural
      control.

PMID- 18714246
TI  - Physiological characteristics of masters-level cyclists.
AB  - Although a considerable amount of research is available describing the
      physiological characteristics of competitive young-adult cyclists, research
      describing these same characteristics in Masters-level cyclists is rare.
      Therefore, the purpose of this study was to describe and compare the effect of
      aging on physiological fitness parameters of Masters-level cyclists in an attempt
      to provide normative fitness data. Thirty-two male cyclists (35-73 years)
      completed one 15-minute economy test and one graded exercise test (GXT) on a
      cycle ergometer. During the GXT, maximal oxygen uptake ([latin capital V with dot
      above]o2max), maximal heart rate (HRmax), the first (VT1) and second (VT2)
      ventilatory thresholds, and peak power output (PPO) were recorded. For the
      purpose of analysis, subjects were allocated into three age groups (35-45 years,
      45-54 years, >=55 years). Maximal oxygen uptake and absolute PPO were
      significantly lower among subjects 55 years and older (45.9 +/- 4.6 mL x kg(-1) x
      min(-1) and 324 +/- 51 W, respectively) compared with the 45- to 54-year group
      (54.2 +/- 6.6 mL x kg(-1) x min(-1) and 392 +/- 36 W, respectively), and both
      were significantly less compared with the 35- to 44-year group (60.7 +/- 5.1 mL x
      kg(-1) x min(-1) and 434 +/- 32 W, respectively). Maximal heart rate was
      significantly greater in both the 35- to 44-year and 45- to 54-year age groups
      compared with the >=55-year group. The first ventilatory threshold was
      significantly greater in the subjects who were 55 years and older group compared
      with the 35- to 44-year and 45- to 54-year age groups, and VT2 was significantly
      greater in subjects 55 years and older compared with the 35- to 44-year group.
      Economy was not different amongst groups. In conclusion, increases in age
      resulted in a significant reduction in fitness parameters across age groups. The
      comparison of the fitness characteristics of Masters-level cyclists with
      established young-adult cyclist data should be avoided, because this may lead to
      inaccurate assessments of fitness.

PMID- 18714248
TI  - Acute effects of static and ballistic stretching on measures of strength and
      power.
AB  - Preactivity stretching is commonly performed by athletes as part of their warm-up
      routine. However, the most recent literature questions the effectiveness of
      preactivity stretching. One limitation of this research is that the stretching
      duration is not realistic for most athletes. Therefore, the purpose of this study
      was to determine the effects of a practical duration of acute static and
      ballistic stretching on vertical jump (VJ), lower-extremity power, and quadriceps
      and hamstring torque. Twenty-four subjects performed a 5-minute warm-up followed
      by each of the following three conditions on separate days with order
      counterbalanced: static stretching, ballistic stretching, or no-stretch control
      condition. Vertical jump was determined with the Vertec VJ system and was also
      calculated from the ground-reaction forces collected from a Kistler force plate,
      which also were used to calculate power. Torque output of the quadriceps and
      hamstrings was measured through knee extension and flexion on the Biodex System 3
      Dynamometer at 60 degrees x s(-1). Data normalized for body weight were analyzed
      using five separate, 3 (stretch condition) x 2 (gender) analysis-of-variance
      procedures with repeated measures on the factor of stretch condition. The gender
      x stretch interaction was not significant for any of the four measures,
      suggesting that the stretching conditions did not affect men and women
      differently. The results of this study reveal that static and ballistic
      stretching did not affect VJ, or torque output for the quadriceps and hamstrings.
      Despite no adverse effect on VJ, stretching did cause a decrease in lower
      extremity power, which was surprising. Because of the mixed results, strength
      coaches would be better served to use dynamic stretching before activity; this
      has been consistently supported by the literature.

PMID- 18714249
TI  - The effect of static stretching on phases of sprint performance in elite soccer
      players.
AB  - The purpose of this study was to determine which phase of a 30-m sprint
      (acceleration and/or maximal velocity) was affected by preperformance static
      stretching. Data were collected from 20 elite female soccer players. On two
      nonconsecutive days, participants were randomly assigned to either the stretch or
      no-stretch condition. On the first day, the athletes in the no-stretch condition
      completed a standard warm-up protocol and then performed three 30-m sprints, with
      a 2-minute rest between each sprint. The athletes in the stretch condition
      performed the standard warm-up protocol, completed a stretching routine of the
      hamstrings, quadriceps, and calf muscles, and then immediately performed three 30
      m sprints, also with a 2-minute rest between each sprint. On the second day, the
      groups were reversed, and identical procedures were followed. One-way repeated
      measures analyses of variance revealed a statistically significant difference in
      acceleration (p < 0.0167), maximal-velocity sprint time (p < 0.0167), and overall
      sprint time (p < 0.0167) between the stretch and no-stretch conditions. Static
      stretching before sprinting resulted in slower times in all three performance
      variables. These findings provide evidence that static stretching exerts a
      negative effect on sprint performance and should not be included as part of the
      preparation routine for physical activity that requires sprinting.

PMID- 18714250
TI  - Influence of closed skill and open skill warm-ups on the performance of speed,
      change of direction speed, vertical jump, and reactive agility in team sport
      athletes.
AB  - In this study, we evaluated the efficacy of two different dynamic warm-up
      conditions, one that was inclusive of open skills (i.e., reactive movements) and
      one that included only preplanned dynamic activities (i.e., closed skills) on the
      performance of speed, change of direction speed, vertical jump, and reactive
      agility in team sport athletes. Fourteen (six male, eight female) junior (mean +/
      SD age, 16.3 +/- 0.7 year) basketball players participated in this study.
      Testing was conducted on 2 separate days using a within-subjects cross-over study
      design. Each athlete performed a standardized 7-minute warm-up consisting of
      general dynamic movements and stretching. After the general warm-up, athletes
      were randomly allocated into one of two groups that performed a dynamic 15-minute
      warm-up consisting entirely of open or closed skills. Each of the warm-up
      conditions consisted of five activities of 3 minute duration. At the completion
      of the warm-up protocol, players completed assessments of reactive agility, speed
      (5-, 10-, and 20-m sprints), change of direction speed (T-test), and vertical
      jump. No significant differences (p > 0.05) were detected among warm-up
      conditions for speed, vertical jump, change of direction speed, and reactive
      agility performances. The results of this study demonstrate that either open
      skill or closed skill warm-ups can be used effectively for team sport athletes
      without compromising performance on open skill and closed skill tasks.

PMID- 18714251
TI  - Effectiveness of active versus passive recovery strategies after futsal games.
AB  - This study aimed to investigate the effects of immediate postgame recovery
      interventions (seated rest, supine electrostimulation, low-intensity land
      exercises, and water exercises) on anaerobic performance (countermovement jump
      [CMJ], bounce jumping, 10-m sprint), hormones (salivary cortisol, urinary
      catecholamines), and subjective ratings (rate of perceived exertion [RPE], leg
      muscle pain, Questionnaire of Recovery Stress for Athletes [RestQ Sport], 10
      point Likert scale), and hours of sleep of futsal players. Heart rate (HR), blood
      lactate, and RPE were used to evaluate the intensity of 4 futsal games in 10
      players using a crossover design (P < 0.05), randomly allocating athletes to 1 of
      the 4 recovery interventions at the end of each game. No significant difference
      emerged between HR, blood lactate, RPE, and level of hydration of the games. A
      significant difference (P < 0.001) between games emerged for total urinary
      catecholamines, with an increase from the first to the second game and a gradual
      reduction up to the fourth game. After the game, significant reductions in CMJ (P
      < 0.001) and 10-m sprints (P < 0.05) emerged. No significant difference was found
      between recovery interventions for anaerobic performances, hormones, muscle pain,
      and RestQ Sport. Even though a well-balanced diet, rehydration, and controlled
      lifestyle might represent a sufficient recovery intervention in young elite
      athletes, the players perceived significantly increased benefit (P < 0.01) from
      the electrostimulation (7.8 +/- 1.4 points) and water exercises (7.6 +/- 2.1
      points) compared to dry exercises (6.6 +/- 1.8 points) and seated rest (5.2 +/-
      0.8 points.), which might improve their attitude toward playing. To induce
      progressive hormonal adaptation to the high exercise load of multiple games, in
      the last 2 weeks of the preseason, coaches should organize friendly games at a
      level similar to that of the competitive season.

PMID- 18714252
TI  - Hydration, thermoregulation, and performance effects of two sport drinks during
      soccer training sessions.
AB  - In the present study, we aimed to compare the thermoregulatory response and
      soccer-specific training performance aspects of two commercially available sport
      drinks, both of similar carbohydrate concentration, but one containing 5.2%
      glycerol. Ten players participated in two similar outdoor training sessions and
      were randomly assigned to each of two drinks: a carbohydrate (C) beverage or a
      carbohydrate-glycerol (CG) beverage. Players consumed 500 mL of C or CG 30
      minutes pre-exercise and at half-time. Pre- and postexercise body mass, core
      temperature (CT), and heart rate (HR) were recorded, and urine and blood samples
      were taken. No difference was observed between days for wet bulb globe
      temperature (session 1: 17.0 +/- 1.1 degrees C, session 2: 16.9 +/- 1.1 degrees
      C; P = 0.944). The degree of dehydration (% Delta BM) was greater after the C
      trial (P = 0.041). Similarly, percent change in plasma volume was greater in the
      C trial (P = 0.049). No overall main affect was observed between CT and mean
      exercise HRs during either training session (CT: P = 0.350; mean HR: P = 0.256),
      and there was no difference observed between groups in time to failure during the
      session-ending fatigue test (P = 0.547). Ingestion of a CG beverage provided
      players with better hydration than C alone. However, if training sessions are
      short (<75 minute), with adequate time for recovery, both drinks are sufficient
      for maintaining performance intensities during soccer-specific training.

PMID- 18714253
TI  - Effects of hydration state and resistance exercise on markers of muscle damage.
AB  - It is well established that resistance exercise can damage muscle tissue, but the
      combined effects of hypohydration and resistance exercise on muscle damage are
      unclear. Two common circulating markers of muscle damage, myoglobin (Mb) and
      creatine kinase (CK) may be attenuated by fluid ingestion post-exercise. The
      purpose of this study was to examine the combined effect of resistance exercise
      and hydration state on muscle damage. Seven healthy resistance-trained males (age
      = 23 +/- 4 years; body mass = 87.8 +/- 6.8 kg; body fat = 11.5 +/- 5.2%)
      completed 3 identical resistance exercise bouts (6 sets of up to 10 repetitions
      of the back squat) in different hydration states: euhydrated (HY0), hypohydrated
      approximately 2.5% body mass (HY2.5), and hypohydrated approximately 5.0% body
      mass (HY5). Subjects achieved desired hydration states via controlled water
      deprivation, exercise-heat stress, and fluid intake. Both Mb and CK were measured
      during euhydrated rest (PRE). Mb was also measured immediately post-exercise, 1
      hour (+1H) and 2 hours (+2H) post-exercise; CK was measured at 24 and 48 hours
      post-exercise. Body mass decreased 0.2 +/- 0.4%, 2.4 +/- 0.4%, and 4.8 +/- 0.4%
      during HY0, HY2.5, and HY5, respectively. Mb concentrations increased
      significantly (effect size >or=1, p < 0.05) from PRE (2.6 +/- 1.1, 3.5 +/- 2.8,
      and 3.2 +/- 1.6 nmol x L(-1)) to +1H (5.3 +/- 3.4, 6.8 +/- 3.2, and 7.6 +/- 2.8
      nmol x L(-1)), and +2H (5.5 +/- 3.8, 6.2 +/- 3.0, and 7.2 +/- 3.0 nmol x L(-1))
      for HY0, HY2.5, and HY5, respectively, but were not significantly different
      between trials. CK concentrations remained within the normal resting range at all
      time points. Thus, hypohydration did not enhance muscle damage following the
      resistance exercise challenge. Despite these results, athletes are encouraged to
      commence exercise in a euhydrated state to maximize endogenous hormonal,
      mechanical, and metabolic benefits.

PMID- 18714275
TI  - Comparison of two treatment approaches for prostate cancer: intensity-modulated
      radiation therapy combined with 125I seed-implant brachytherapy or 125I seed
      implant brachytherapy alone.
AB  - The purpose of the present study was to assess the results of two different
      treatment approaches for clinically localized prostate cancer: intensity
      modulated radiation therapy (IMRT) followed by 125I seed-implant brachytherapy
      and 125I seed-implant brachytherapy alone. We studied our 30 most recent
      consecutive patients. The sample population consisted of 15 cases treated with
      IMRT (50.4 Gy) followed by 125I seed-implant boost (95 Gy), and 15 cases treated
      with 125I seed implant only (144 Gy). We analyzed established dosimetric indices
      and various clinical parameters. In addition, we also evaluated and compared the
      acute urinary morbidities of the two treatment approaches, as assessed by the
      international prostate symptom score (IPSS). In our series, acute urinary
      morbidity was slightly increased with IMRT followed by 125I seed-implant
      brachytherapy as compared with 125I seed-implant brachytherapy alone. In
      addition, we observed no statistically significant correlation between the IPSS
      and the maximum or mean urethral dose. The combination of IMRT and seed-implant
      brachytherapy presents an alternative opportunity to treat clinically localized
      prostate cancer. The full potential of the procedure needs to be further
      investigated.

PMID- 18714276
TI  - Commissioning a fast Monte Carlo dose calculation algorithm for lung cancer
      treatment planning.
AB  - A commercial Monte Carlo simulation package, NXEGS 1.12 (NumeriX LLC, New York,
      NY), was commissioned for photon-beam dose calculations. The same sets of
      measured data from 6-MV and 18-MV beams were used to commission NXEGS and
      Pinnacle 6.2b (Philips Medical Systems, Andover, MA). Accuracy and efficiency
      were compared against the collapsed cone convolution algorithm implemented in
      Pinnacle 6.2b, together with BEAM simulation (BEAMnrc 2001: National Research
      Council of Canada, Ottawa, ON). We investigated a number of options in NXEGS: the
      accuracy of fast Monte Carlo, the re-implementation of EGS4, post-processing
      technique (dose de-noising algorithm), and dose calculation time. Dose
      distributions were calculated with NXEGS, Pinnacle, and BEAM in water, lung-slab,
      and air-cylinder phantoms and in a lung patient plan. We compared the dose
      distributions calculated by NXEGS, Pinnacle, and BEAM. In a selected region of
      interest (7725 voxels) in the lung phantom, all but 1 voxel had a gamma (3% and 3
      mm thresholds) of 1 or less for the dose difference between the NXEGS re
      implementation of EGS4 and BEAM, and 99% of the voxels had a gamma of 1 or less
      for the dose difference between NXEGS fast Monte Carlo and BEAM. Fast Monte Carlo
      with post-processing was up to 100 times faster than the NXEGS re-implementation
      of EGS4, while maintaining +/- 2% statistical uncertainty. With air
      inhomogeneities larger than 1 cm, post-processing preserves the dose
      perturbations from the air cylinder. When 3 or more beams were used, fast Monte
      Carlo with post-processing was comparable to or faster than Pinnacle 6.2b
      collapsed cone convolution.

PMID- 18714277
TI  - Dosimetric characteristics of dual-layer multileaf collimation for small-field
      and intensity-modulated radiation therapy applications.
AB  - The purpose of the present work was to measure the performance characteristics in
      the penumbra region and on the leaf-end of an innovative dual-layer micro
      multileaf collimator (DmMLC). The DmMLC consists of two orthogonal (upper and
      lower) layers of leaves; a standard MLC consists of one layer. The DmMLC provides
      unique performance characteristics in smoothing dose undulation, reducing leaf
      end transmission, and reducing MLC field dependence of the leaf stepping angle.
      Two standard MLCs (80-leaf and 120-leaf versions: Varian Medical Systems, Palo
      Alto, CA), a DmMLC (AccuKnife: Initia Medical Technology, Canton, MA), and a
      Cerrobend (Cerro Metal Products, Bellefonte, PA) block were used in performance
      studies involving a triangular field, a cross leaf-end field, and a circular
      field. Measurements were made with 6-MV X-rays and extended dose range film at a
      depth of 5 cm in Solid Water (Gammex rmi, Middleton, WI) at a source-axis
      distance of 100 cm. The field penumbra width measured between the 20% and 80%
      isodose lines through the MLC-80, MLC-120, DmMLC, and Cerrobend block were 9.0,
      5.0, 3.0, and 2.0 mm respectively. The dose undulation amplitude of the 50%
      isodose line was measured as 5.5, 2.0, and 0.5 mm for the MLC-80, MLC-120, and
      DmMLC respectively. The planar dose difference between the MLC-80, MLC-120, and
      DmMLC against Cerrobend block was measured as ranging at +/-52.5%, +/-35.0%, and
      +/-20.0% respectively. The leaf-end transmission was measured at 22.4% in maximum
      and 15.4% in average when closing a single layer of the DmMLC, and at 2.4% in
      maximum and 2.1% in average when closing both layers. The MLC dependence of the
      leaf stepping angle with the DmMLC ranged from 45 degrees to 90 degrees. The
      standard MLC leaf stepping angle ranged from 0 degrees to 90 degrees. In
      conclusion, the dose undulation, leafend transmission, and MLC field dependence
      of the leaf stepping angle with the DmMLC were remarkably reduced as compared
      with those of the standard MLCs. And as compared with Cerrobend block, the DmMLC
      provided very comparable performance in field-edge smoothing and in the shaping
      of complex fields.

PMID- 18714278
TI  - Design and implementation of a head-and-neck phantom for system audit and
      verification of intensity-modulated radiation therapy.
AB  - The head and neck is a challenging anatomic site for intensity-modulated
      radiation therapy (IMRT), requiring thorough testing of planning and treatment
      delivery systems. Ideally, the phantoms used should be anatomically realistic,
      have radiologic properties identical to those of the tissues concerned, and allow
      for the use of a variety of devices to verify dose and dose distribution in any
      target or normaltissue structure. A phantom that approaches the foregoing
      characteristics has been designed and built; its specific purpose is verification
      for IMRT treatments in the head-andneck region. This semi-anatomic phantom, HANK,
      is constructed of Perspex (Imperial Chemical Industries, London, U.K.) and
      provides for the insertion of heterogeneities simulating air cavities in a range
      of fixed positions. Chamber inserts are manufactured to incorporate either a
      standard thimble ionization chamber (0.125 cm3: PTW, Freiburg, Germany) or a
      smaller PinPoint chamber (0.015 cm3: PTW), and measurements can be made with
      either chamber in a range of positions throughout the phantom. Coronal films can
      also be acquired within the phantom, and additional solid blocks of Perspex allow
      for transverse films to be acquired within the head region. Initial studies using
      simple conventional head-and-neck plans established the reproducibility of the
      phantom and the measurement devices to within the setup uncertainty of +/- 0.5
      mm. Subsequent verification of 9 clinical head-and-neck IMRT plans demonstrated
      the efficacy of the phantom in making a range of patient-specific dose
      measurements in regions of dosimetric and clinical interest. Agreement between
      measured values and those predicted by the Pinnacle3 treatment planning system
      (Philips Medical Systems, Andover, MA) was found to be generally good, with a
      mean error on the calculated dose to each point of +0.2% (range: -4.3% to +2.2%;
      n = 9) for the primary planning target volume (PTV), -0.1% (range: -1.5% to
      +2.0%; n = 8) for the nodal PTV, and +0.0% (range: -1.8% to +4.3%, n = 9) for the
      spinal cord. The suitability of the phantom for measuring combined dose
      distributions using radiographic film was also evaluated. The phantom has proved
      to be a valuable tool in the development and implementation of clinical head-and
      neck IMRT, allowing for accurate verification of absolute dose and dose
      distributions in regions of clinical and dosimetric interest.

PMID- 18714279
TI  - The application of distance transformation on parameter optimization of inverse
      planning in intensity-modulated radiation therapy.
AB  - In inverse planning for intensity-modulated radiation therapy (IMRT), the dose
      specification and related weighting factor of an objective function for involved
      organs is usually predefined by a single value and then iteratively optimized,
      subject to a set of dose-volume constraints. Because the actual dose distribution
      is essentially non-uniform and considerably affected by the geometric shape and
      distribution of the anatomic structures involved, the spatial information
      regarding those structures should be incorporated such that the predefined
      parameter distribution is made to approach the clinically expected distribution.
      Ideally, these parameter distributions should be predefined on a voxel basis in a
      manual method. However, such an approach is too time-consuming to be feasible in
      routine use. In the present study, we developed a computer-aided method to
      achieve the goal described above, producing a non-uniform parameter distribution
      based on spatial information about the anatomic structures involved. The method
      consists of two steps: Use distance transformation technique to calculate the
      distance distribution of the structures. Based on the distance distribution,
      produce the parameter distribution via a function guided by prior knowledge. We
      use two simulated cases to examine the effectiveness of the method. The results
      indicate that application of a non-uniform parameter distribution produced by
      distance transformation clearly improves dose-sparing of critical organs without
      compromising dose coverage of the planning target.

PMID- 18714280
TI  - The investigation on the location effect of external markers in respiratory-gated
      radiotherapy.
AB  - PURPOSE: To investigate the effect of the marker placement on the correlation
      relationship between the motions of external markers and the internal target
      under different breathing patterns for several lung cancer patients. METHOD AND
      MATERIAL: To monitor and record simultaneous motions of internal target and
      associated surrogate markers during respiratory gated radiotherapy, an infrared
      camera system synchronized with a medical simulator was installed in our
      institute. Multiple external markers were placed on the patients' chest wall with
      proper geometrical arrangement in closely monitoring the motion of skin near
      tumor. The motion signals of three breathing sessions (free breathing, breath
      holding, and free breathing after breath-holding) were recorded and the quality
      of correlation between them was analyzed. For a single marker motion, its
      correlation with the internal target was analyzed using cross-covariance
      function. For the multiple markers, their correlation with the internal target
      was analyzed based on additive model. RESULT: Seven patients undergoing
      radiotherapy with right upper or middle lobe lesions were enrolled in this study.
      Statistic analysis based on the internal-external motion signals shows that the
      effect of marker location on the quality of its correlation with the internal
      target is varied from patient to patient. There was no specific marker location
      where consistently demonstrated superior quality of correlation with the internal
      target motion over three breathing sessions for all patients. As the composite
      surrogate signal which was generated from the motions of multiple external
      markers was used to correlate the internal target motion, significant improvement
      of the quality of correlation was achieved. CONCLUSION: The correlation of
      external marker to the internal target could be influenced by several factors
      such as patient population, marker locations, and breathing patterns,
      considerably. The quality of correlation and predictability to the internal
      target furnished by a single external marker is inferior to that of the composite
      signal generated from multiple external markers. The use of composite signal
      shows great potential in improving the predictability of internal target motion
      and presents an effective way to track tumor more accurately.

PMID- 18714281
TI  - Cylindrical coordinate based TG-43U1 parameters for dose calculation around
      elongated brachytherapy sources.
AB  - In 2001, the use of cylindrical coordinates was demonstrated to be more suitable
      than was the use of polar coordinates for accurate computer calculations during
      treatment planning for 192Ir intravascular brachytherapy sources. In the present
      work, we investigated the applicability of cylindrical coordinate-based TG-43U1
      parameters for dosimetric evaluation and dose calculations for RadioCoil 103Pd
      sources (RadioMed Corporation, Tyngsboro, MA) 1.0-cm to 6.0-cm long. For brevity,
      only the results for sources 1.0-cm, 3.0-cm, and 5.0-cm long are presented here.
      Dosimetric characteristics of RadioCoil 103Pd sources were calculated in liquid
      water using the Monte Carlo simulation technique. To demonstrate the suitability
      of this methodology, the Monte Carlo-simulated dose profiles for a RadioCoil
      103Pd source 5.0-cm long at radial distances of 0.5 cm, 0.9 cm, and 1.25 cm were
      compared with calculated data using TG-43U1 parameters in the polar and
      cylindrical coordinate systems. In addition, we also used a source 1.0-cm long
      parameterized using cylindrical coordinates to investigate the application of a
      linear segmented source (LSS) model originally introduced by our group. The
      results indicate that, for dose calculation around elongated brachytherapy
      sources, cylindrical coordinate-based TG-43U1 parameters more accurately
      represent the dose distribution around an elongated source than the polar
      coordinate-based parameters. In addition, the LSS model, in conjunction with the
      cylindrical coordinate-based parameters for a source 1.0-cm long, can be used to
      replicate the dose distribution around any integral source length. This process
      eliminates the need to collect and enter data for multiple source lengths into
      treatment planning systems.

PMID- 18714282
TI  - Dosimetric evaluation of Plastic Water Diagnostic-Therapy.
AB  - High-precision radiotherapy planning and quality assurance require accurate
      dosimetric and geometric phantom measurements. Phantom design requires materials
      with mechanical strength and resilience, and dosimetric properties close to those
      of water over diagnostic and therapeutic ranges. Plastic Water Diagnostic Therapy
      (PWDT: CIRS, Norfolk, VA) is a phantom material designed for water equivalence in
      photon beams from 0.04 MeV to 100 MeV; the material has also good mechanical
      properties. The present article reports the results of computed tomography (CT)
      imaging and dosimetric studies of PWDT to evaluate the suitability of the
      material in CT and therapy energy ranges. We characterized the water equivalence
      of PWDT in a series of experiments in which the basic dosimetric properties of
      the material were determined for photon energies of 80 kVp, 100 kVp, 250 kVp, 4
      MV, 6 MV, 10 MV, and 18 MV. Measured properties included the buildup and
      percentage depth dose curves for several field sizes, and relative dose factors
      as a function of field size. In addition, the PWDT phantom underwent CT imaging
      at beam qualities ranging from 80 kVp to 140 kVp to determine the water
      equivalence of the phantom in the diagnostic energy range. The dosimetric
      quantities measured with PWDT agreed within 1.5% of those determined in water and
      Solid Water (Gammex rmi, Middleton, WI). Computed tomography imaging of the
      phantom was found to generate Hounsfield numbers within 0.8% of those generated
      using water. The results suggest that PWDT material is suitable both for regular
      radiotherapy quality assurance measurements and for intensity-modulated radiation
      therapy (IMRT) verification work. Sample IMRT verification results are presented.

PMID- 18714283
TI  - Inhomogeneity correction and the analytic anisotropic algorithm.
AB  - The ability of the analytic anisotropic algorithm (AAA), a superposition-
      convolution algorithm implemented in the Eclipse (Varian Medical Systems, Palo
      Alto, CA) treatment planning system (TPS), to accurately account for the presence
      of inhomogeneities in simple geometries is examined. The goal of 2% accuracy, as
      set out by the American Association of Physicists in Medicine Task Group 65,
      serves as a useful benchmark against which to evaluate the inhomogeneity
      correction capabilities of this treatment planning algorithm. A planar geometry
      phantom consisting of upper and lower layers of Solid Water (Gammex rmi,
      Middleton, WI) separated by a heterogeneity region of variable thickness, is
      modeled within the Eclipse TPS. Results obtained with the AAA are compared with
      experimental measurements. Seven different materials, spanning the range from air
      to aluminum, constitute the inhomogeneity layer. In general, the AAA overpredicts
      dose beyond low-density regions and underpredicts dose distal to volumes of high
      density. In many cases, the deviation between the AAA and experimental results
      exceeds the Task Group 65 target of 2%. The source of these deviations appears to
      arise from an inability of the AAA to correctly account for altered attenuation
      along primary ray paths.

PMID- 18714284
TI  - Determination of an optimal organ set to implement deformations to support four
      dimensional dose calculations in radiation therapy planning.
AB  - Surface-based deformable image registration to generate a four-dimensional (4D)
      dose calculation in radiation treatment planning requires the selection of a set
      of organ contours to represent a basis set to generate anatomic deformation. The
      purpose of the present work was to determine the optimal set of organs needed to
      generate a basis set for deformation in treatment planning for thoracic tumors
      such that the required computations are minimized but dose accuracy is high.
      Using retrospectively reviewed records, we calculated 4D dose distributions based
      on treatment plans for 10 patients with thoracic tumors using a deformable model
      algorithm in a research version of a commercial radiation treatment planning
      system. Various combinations of organs (total lungs, heart, spinal cord, external
      body surface) were used to generate the basis set for deformations used in the
      calculations. The external surface contour did not have a noticeable effect on
      the dose calculation. Total lung, heart, and spinal cord together provided an
      adequate set of deformation organs to generate accurate dose deformations. The
      magnitude of calculated dose differences had no obvious relationship to tumor
      parameters, including site, histologic type, disease stage, extent of motion, or
      degree of centralization.

PMID- 18714285
TI  - Editorial--a professional doctorate degree in medical physics.

PMID- 18714290
TI  - Towards a cyberinfrastructure for the biological sciences: progress, visions and
      challenges.
AB  - Biology is an information-driven science. Large-scale data sets from genomics,
      physiology, population genetics and imaging are driving research at a dizzying
      rate. Simultaneously, interdisciplinary collaborations among experimental
      biologists, theorists, statisticians and computer scientists have become the key
      to making effective use of these data sets. However, too many biologists have
      trouble accessing and using these electronic data sets and tools effectively. A
      'cyberinfrastructure' is a combination of databases, network protocols and
      computational services that brings people, information and computational tools
      together to perform science in this information-driven world. This article
      reviews the components of a biological cyberinfrastructure, discusses current and
      pending implementations, and notes the many challenges that lie ahead.

PMID- 18714291
TI  - Leader of the pack: gene mapping in dogs and other model organisms.
AB  - The domestic dog offers a unique opportunity to explore the genetic basis of
      disease, morphology and behaviour. We share many diseases with our canine
      companions, including cancer, diabetes and epilepsy, making the dog an ideal
      model organism for comparative disease genetics. Using newly developed resources,
      whole-genome association in dog breeds is proving to be exceptionally powerful.
      Here, we review the different trait-mapping strategies, some key biological
      findings emerging from recent studies and the implications for human health. We
      also discuss the development of similar resources for other vertebrate organisms.

PMID- 18714292
TI  - A three-component Fischer indole synthesis.
AB  - This protocol describes a three-component approach to multiply-substituted
      indoles from nitriles, organometallic reagents and arylhydrazine hydrochloride
      salts. The condensation of organolithium or Grignard reagents with nitriles
      produces metalloimines, which under acidic conditions and in the presence of
      arylhydrazines lead to arylhydrazones, the starting materials for the Fischer
      indole reaction. Combining this approach with the Fischer indole reaction
      produces indoles in an efficient, one-pot process. The procedure takes
      approximately 20 h to complete: 3 h for metalloimine formation, 15 h for the
      Fischer indole reaction and 2 h for isolation and purification.

PMID- 18714293
TI  - Primary culture and phenotyping of murine chondrocytes.
AB  - The culture of chondrocytes is one of the most powerful tools for exploring the
      intracellular and molecular features of chondrocyte differentiation and
      activation. However, chondrocytes tend to dedifferentiate into fibroblasts when
      they are subcultured, which is a major problem. This protocol, involving primary
      cultures to limit dedifferentiation, describes two different methods for
      culturing chondrocytes of different anatomical origins (articular and costal
      chondrocytes, both of which represent hyaline cartilage) from mice. Mice are of
      particular interest for cellular and molecular studies, as many tools suitable
      for use in mice are available. In addition, rapid development of transgenic and
      gene-targeted mice provides powerful instruments for biological studies. The
      protocol can be divided into four stages: isolation of cartilage (15 min per
      animal), isolation of chondrocytes (2 h extended overnight), seeding of
      chondrocytes (1 h 30 min) and growth in culture (6 d). To obtain confluency of
      chondrocytes using this protocol takes 7 d. Methods for phenotyping chondrocytes
      are also provided.

PMID- 18714294
TI  - Cultivating previously uncultured soil bacteria using a soil substrate membrane
      system.
AB  - Most bacteria are recalcitrant to traditional cultivation in the laboratory. The
      soil substrate membrane system provides a simulated environment for the
      cultivation of previously undescribed soil bacteria as microcolonies. The system
      uses a polycarbonate membrane as a solid support for growth and soil extract as
      the substrate. Diverse microcolonies can be visualized using total bacterial
      staining combined with fluorescence in situ hybridization (FISH) after 7-10-d
      incubation. Molecular typing shows that the majority of microcolony-forming
      bacteria recovered using this protocol were resistant to growth using standard
      methods. The protocol takes <4 h of bench time over the 10-d period.

PMID- 18714295
TI  - Enzyme assay and activity fingerprinting of hydrolases with the red-chromogenic
      adrenaline test.
AB  - The adrenaline test for enzymes is a colorimetric enzyme assay based on the
      quantification of periodate-sensitive reaction products such as 1,2-diols and 1,2
      aminoalcohols by back-titration of the oxidant with adrenaline to produce
      adrenochrome as an easily detectable red product. The test uses commercial
      reagents and is suitable for screening the activity of various hydrolases. It is
      demonstrated here for testing epoxide hydrolases, lipases and esterases, and for
      activity fingerprinting of these enzymes across substrate series. The complete
      assay requires 2-3 h.

PMID- 18714296
TI  - Noninvasive high-resolution in vivo imaging of cell biology in the anterior
      chamber of the mouse eye.
AB  - There is clearly a demand for an experimental platform that enables cell biology
      to be studied in intact vascularized and innervated tissue in vivo. This platform
      should allow observations of cells noninvasively and longitudinally at single
      cell resolution. For this purpose, we use the anterior chamber of the mouse eye
      in combination with laser scanning microscopy (LSM). Tissue transplanted to the
      anterior chamber of the eye is rapidly vascularized, innervated and regains
      function. After transplantation, LSM through the cornea allows repetitive and
      noninvasive in vivo imaging at cellular resolution. Morphology, vascularization,
      cell function and cell survival are monitored longitudinally using fluorescent
      proteins and dyes. We have used this system to study pancreatic islets, but the
      platform can easily be adapted for studying a variety of tissues and additional
      biological parameters. Transplantation to the anterior chamber of the eye takes
      25 min, and in vivo imaging 1-5 h, depending on the features monitored.

PMID- 18714297
TI  - Quantification of DNA damage products resulting from deamination, oxidation and
      reaction with products of lipid peroxidation by liquid chromatography isotope
      dilution tandem mass spectrometry.
AB  - The analysis of damage products as biomarkers of inflammation has been hampered
      by a poor understanding of the chemical biology of inflammation, the lack of
      sensitive analytical methods and a focus on single chemicals as surrogates for
      inflammation. To overcome these problems, we developed a general and sensitive
      liquid chromatographic tandem mass spectrometry (LC/MS-MS) method to quantify, in
      a single DNA sample, the nucleoside forms of seven DNA lesions reflecting the
      range of chemistries associated with inflammation: 2'-deoxyuridine, 2'
      deoxyxanthosine and 2'-deoxyinosine from nitrosative deamination; 8-oxo-2'
      deoxyguanosine from oxidation; and 1,N(2)-etheno-2'-deoxyguanosine, 1,N(6)-etheno
      2'-deoxyadenosine and 3,N(4)-etheno-2'-deoxycytidine arising from reaction of DNA
      with lipid peroxidation products. Using DNA purified from cells or tissues under
      conditions that minimize artifacts, individual nucleosides are purified by HPLC
      and quantified by isotope-dilution, electrospray ionization LC/MS-MS. The method
      can be applied to other DNA damage products and requires 4-6 d to complete
      depending upon the number of samples.

PMID- 18714298
TI  - Absolute quantitation of intracellular metabolite concentrations by an isotope
      ratio-based approach.
AB  - This protocol provides a method for quantitating the intracellular concentrations
      of endogenous metabolites in cultured cells. The cells are grown in stable
      isotope-labeled media to near-complete isotopic enrichment and then extracted in
      organic solvent containing unlabeled internal standards in known concentrations.
      The ratio of endogenous metabolite to internal standard in the extract is
      determined using mass spectrometry (MS). The product of this ratio and the
      unlabeled standard amount equals the amount of endogenous metabolite present in
      the cells. The cellular concentration of the metabolite can then be calculated on
      the basis of intracellular volume of the extracted cells. The protocol is
      exemplified using Escherichia coli and primary human fibroblasts fed uniformly
      with (13)C-labeled carbon sources, with detection of (13)C-assimilation by liquid
      chromatography-tandem MS. It enables absolute quantitation of several dozen
      metabolites over approximately 1 week of work.

PMID- 18714299
TI  - PCR-amplification of GC-rich regions: 'slowdown PCR'.
AB  - The polymerase chain reaction (PCR) technique has become an indispensable method
      in molecular research. However, PCR-amplification of GC-rich templates is often
      hampered by the formation of secondary structures like hairpins and higher
      melting temperatures. We present a novel method termed 'Slowdown PCR', which
      allows the successful PCR-amplification of extremely GC-rich (>83%) DNA targets.
      The protocol relies on the addition of 7-deaza-2'-deoxyguanosine, a dGTP analog
      to the PCR mixture and a novel standardized cycling protocol with varying
      temperatures. The latter consists of a generally lowered ramp rate of 2.5 degrees
      C s(-1) and a low cooling rate of 1.5 degrees C s(-1) for reaching an annealing
      temperature and is run for 48 cycles. We established this protocol as a versatile
      method not only for amplification of extremely GC-rich regions, but also for
      routine DNA diagnostics and pharmacogenetics for templates with different
      annealing temperatures. The protocol takes 5 h to complete.

PMID- 18714300
TI  - Live visualization of protein synthesis in axonal growth cones by microinjection
      of photoconvertible Kaede into Xenopus embryos.
AB  - Photoconvertible fluorescent proteins, such as Kaede, can be switched
      irreversibly from their native color to a new one. This property can be exploited
      to visualize de novo mRNA translation, because newly synthesized proteins can be
      distinguished from preexisting ones by their color. In this protocol, Kaede cDNA
      linked to the 3' untranslated region (UTR) of beta-actin is delivered into cells
      fated to become the retina by injection into Xenopus blastomeres. Brief exposure
      (6-10 s) to UV light (350-410 nm) of Kaede-positive retinal axons/growth cones
      efficiently converts Kaede from its native green fluorescence to red. The
      reappearance of the green signal reports the synthesis of new Kaede protein. This
      approach can be used to investigate the spatiotemporal control of translation of
      specific mRNAs in response to external stimuli and to test the efficiency of full
      length versus mutant UTRs. The 3-d protocol can be adapted for broad use with
      other photoactivatable fluorescent proteins.

PMID- 18714302
TI  - Nanostructure-initiator mass spectrometry: a protocol for preparing and applying
      NIMS surfaces for high-sensitivity mass analysis.
AB  - Nanostructure-initiator mass spectrometry (NIMS) is a new surface-based MS
      technique that uses a nanostructured surface to trap liquid ('initiator')
      compounds. Analyte materials adsorbed onto this 'clathrate' surface are
      subsequently released by laser irradiation for mass analysis. In this protocol,
      we describe the preparation of NIMS surfaces capable of producing low background
      and high-sensitivity mass spectrometric measurement using the initiator compound
      BisF17. Examples of analytes that adsorb to this surface are small molecules,
      drugs, lipids, carbohydrates and peptides. Typically, NIMS is used to analyze
      samples ranging from simple analytical standards and proteolytic digests to more
      complex samples such as tissues, cells and biofluids. Critical experimental
      considerations of NIMS are described. Specifically, NIMS sensitivity is examined
      as a function of pre-etch cleaning treatment, etching current density, etching
      time, initiator composition, sample concentration, sample deposition method and
      laser fluence. Typically, NIMS surface preparation can be completed in less than
      2 h. Subsequent sample preparation requires 1-5 min, depending on sample
      deposition method. Mass spectrometric data acquisition typically takes 1-30 s per
      sample.

PMID- 18714301
TI  - Kinetic flux profiling for quantitation of cellular metabolic fluxes.
AB  - This protocol enables quantitation of metabolic fluxes in cultured cells.
      Measurements are based on the kinetics of cellular incorporation of stable
      isotope from nutrient into downstream metabolites. At multiple time points, after
      cells are rapidly switched from unlabeled to isotope-labeled nutrient, metabolism
      is quenched, metabolites are extracted and the extract is analyzed by
      chromatography-mass spectrometry. Resulting plots of unlabeled compound versus
      time follow variants of exponential decay, with the flux equal to the decay rate
      multiplied by the intracellular metabolite concentration. Because labeling is
      typically fast (t(1/2)<or=5 min for central metabolites in Escherichia coli),
      variations on this approach can effectively probe dynamically changing metabolic
      fluxes. This protocol is exemplified using E. coli and nitrogen labeling, for
      which quantitative flux data for approximately 15 metabolites can be obtained
      over 3 d of work. Applications to adherent mammalian cells are also discussed.

PMID- 18714303
TI  - Development, validation and implementation of immobilized metal affinity for
      phosphochemicals (IMAP)-based high-throughput screening assays for low-molecular
      weight compound libraries.
AB  - This protocol describes assay development, validation and implementation of
      automated immobilized metal affinity for phosphochemicals (IMAP)-based
      fluorescence polarization (FP) and time-resolved fluorescence resonance energy
      transfer (TR-FRET) high-throughput screening (HTS) assays for identification of
      low-molecular-weight kinase inhibitors. Both procedures are performed in
      miniaturized kinase reaction volumes and involve the stepwise addition of test or
      control compounds, enzyme and substrate/ATP. Kinase reactions are stopped by
      subsequent addition of IMAP-binding buffer. Assay attributes of the IMAP FP and
      TR-FRET methodologies are described. HTS assays developed using these procedures
      should result in Z-factors and low assay variability necessary for robust HTS
      assays. Providing that the required reagents and equipment are available, one
      scientist should be able to develop a 384-well, miniaturized HTS assay in
      approximately 6-8 weeks. Specific automated HTS assay conditions will determine
      the number of assay plates processed in a screening session, but two scientists
      should expect to process between 100 and 150 assay plates in one 8-h screening
      day.

PMID- 18714304
TI  - The fluorometric microculture cytotoxicity assay.
AB  - The fluorometric microculture cytotoxicity assay (FMCA) is a nonclonogenic
      microplate-based cell viability assay used for measurement of the cytotoxic
      and/or cytostatic effect of different compounds in vitro. The assay is based on
      hydrolysis of the probe, fluorescein diacetate (FDA) by esterases in cells with
      intact plasma membranes. The assay is available as both a semiautomated 96-well
      plate setup and a 384-well plate version fully adaptable to robotics.
      Experimental plates are prepared with a small amount of drug solution and can be
      stored frozen. Cells are seeded on the plates and cell viability is evaluated
      after 72 h. The protocol described here is applicable both for cell lines and
      freshly prepared tumor cells from patients and is suitable both for screening in
      drug development and as a basis for a predictive test for individualization of
      anticancer drug therapy.

PMID- 18714305
TI  - Detection of two mRNA species at single-cell resolution by double-fluorescence in
      situ hybridization.
AB  - Here we describe a fluorescence in situ hybridization protocol that allows for
      the detection of two mRNA species in fresh frozen brain tissue sections. This
      protocol entails the simultaneous and specific hybridization of hapten-labeled
      riboprobes to complementary mRNAs of interest, followed by probe detection via
      immunohistochemical procedures and peroxidase-mediated precipitation of tyramide
      linked fluorophores. In this protocol we describe riboprobes labeled with
      digoxigenin and biotin, though the steps can be adapted to labeling with other
      haptens. We have used this approach to establish the neurochemical identity of
      sensory-driven neurons and the co-induction of experience-regulated genes in the
      songbird brain. However, this procedure can be used to detect virtually any
      combination of two mRNA populations at single-cell resolution in the brain, and
      possibly other tissues. Required controls, representative results and
      troubleshooting of important steps of this procedure are presented. After tissue
      sections are obtained, the total length of the procedure is 2-3 d.

PMID- 18714306
TI  - Phase I study of noninvasive imaging of adenovirus-mediated gene expression in
      the human prostate.
AB  - To monitor noninvasively potentially therapeutic adenoviruses for cancer, we have
      developed a methodology based on the sodium iodide symporter (NIS). Men with
      clinically localized prostate cancer were administered an intraprostatic
      injection of a replication-competent adenovirus, Ad5-yCD/utTK(SR39)rep-hNIS,
      armed with two suicide genes and the NIS gene. NIS gene expression (GE) was
      imaged noninvasively by uptake of Na(99 m)TcO(4) in infected cells using single
      photon emission-computed tomography (SPECT). The investigational therapy was safe
      with 98% of the adverse events being grade 1 or 2. GE was detected in the
      prostate in seven of nine (78%) patients at 1 x 10(12) virus particles (vp) but
      not at 1 x 10(11) vp. Volume and total amount of GE was quantified by SPECT.
      Following injection of 1 x 10(12) vp in 1 cm(3), GE volume (GEV) increased to a
      mean of 6.6 cm(3), representing, on average, 18% of the total prostate volume.
      GEV and intensity peaked 1-2 days after the adenovirus injection and was
      detectable in the prostate up to 7 days. Whole-body imaging demonstrated
      intraprostatic gene expression, and there was no evidence of extraprostatic
      dissemination of the adenovirus by SPECT imaging. The results demonstrate that
      noninvasive imaging of adenovirus-mediated gene therapy in humans is feasible and
      safe.

PMID- 18714307
TI  - Expanded repertoire of AAV vector serotypes mediate unique patterns of
      transduction in mouse brain.
AB  - A wide diversity of adeno-associated virus (AAV) structural proteins uncovered
      from latent genomes in primate tissue has expanded the number of AAV vector
      serotypes, which can potentially confer unique cell tropism to the vector. We
      evaluated 17 of these vectors in the mouse brain using green fluorescent protein
      (GFP) as a reporter gene. A rapid initial evaluation was performed by neonatal
      lateral ventricle injections. Vectors made with capsids hu.32, hu.37, pi.2,
      hu.11, rh.8, hu.48R3, and AAV9 for comparison were selected for further analysis
      based on their ability to transduce large numbers of cells and result in novel
      patterns of cell transduction. These vectors were injected into adult brains in
      four major structures (cortex, striatum, hippocampus, and thalamus), and all were
      found to transduce neurons. In addition, hu.32, hu.11, pi.2, hu.48R3, and rh.8
      resulted in GFP expression in some astrocytes or oligodendrocytes. AAVs rh.8,
      pi.2, hu.32, and hu.11 also appeared to result in neuronal transport of the
      vector genome. Vector transport was studied by a single unilateral injection into
      the hippocampus and vector genome was found in projection sites of the
      hippocampus. These unique patterns of cell transduction expand the potential
      repertoire for targeting AAV vectors to selected subsets of brain cells.

PMID- 18714308
TI  - Gene-eluting stents: adenovirus-mediated delivery of eNOS to the blood vessel
      wall accelerates re-endothelialization and inhibits restenosis.
AB  - Drug-eluting stents for coronary artery disease results in inhibition of smooth
      muscle cell (SMC) and endothelial cells which may increase the risk of stent
      thrombosis. In this study, we attempted to enhance re-endothelialization of
      deployed stents while simultaneously inhibiting intimal hyperplasia by
      overexpression of endothelial nitric oxide synthase (eNOS) delivery in the
      vasculature using an adenovirus gene-eluting stent. Re-endothelialization was
      significantly greater in vessels obtained from normocholesterolemic animals at
      day 14 (85.34% +/- 7.38 versus 62.66% +/- 10.49; P < 0.05) and day 28 (91.1% +/-
      10 versus 63.1% +/- 22; P < 0.05) and hypercholesterolemic animals (96.97% +/-
      3.2 versus 28.33% +/- 38.76; P < 0.05) at day 28 with AdeNOS-eluting stents. At
      day 28, there was a significant increase in the lumen size [AdeNOS 2.73 mm(2) +/-
      1.18, AdbetaGal 0.98 mm(2) +/- 0.98, phosphorylcholine (PC) 1.87 mm(2) +/- 1.18;
      P < 0.05], and a significant reduction in neointimal formation (AdeNOS 2.32 mm(2)
      +/- 1.13, AdbetaGal 3.73 mm(2) +/- 0.95, PC 3.2 mm(2) +/- 0.94; P < 0.05), and
      percent restenosis (AdeNOS 45.23 +/- 20.81, AdbetaGal 79.6 +/- 20.31, PC 70.16 +/
      22.2; P < 0.05) in AdeNOS-stented vessels in comparison with controls from
      hypercholesterolemic animals, assessed by morphometry and quantitative coronary
      angiography (AdeNOS 15.95% +/- 7.63, AdbetaGal 56.9% +/- 38.6, PC 58 +/- 34.6; P
      < 0.05). Stent-based delivery of AdeNOS results in enhanced endothelial
      regeneration and reduction in neointimal formation as compared with controls.
      This seems to be a promising treatment strategy for preventing in-stent
      restenosis (ISR) while simultaneously reducing the risk of stent thrombosis.

PMID- 18714309
TI  - Targeting of adenovirus vectors to the LRP receptor family with the high-affinity
      ligand RAP via combined genetic and chemical modification of the pIX capsomere.
AB  - Adenovirus (Ad) vector targeting requires presentation of specific ligands on the
      virion's surface. Geneti-chemical targeting is based on the genetic introduction
      of cysteine residues bearing reactive thiol groups into solvent-accessible
      capsomeres of the virion and subsequent chemical coupling of ligands. Here, we
      exploited this technology to modify the pIX capsomere with high-affinity ligands.
      Genetic introduction of C-terminal cysteines to pIX allowed for specific coupling
      of full-length proteins to the virion, while not affecting vector production.
      Direct comparison of the two high-affinity ligands receptor- associated protein
      (RAP) and transferrin (Tf) revealed that targeting after coupling of a high
      affinity ligand to pIX presumably requires release of the ligand from its
      receptor after cell entry. In addition, data obtained by live cell imaging of
      labeled vector particles demonstrated that coupling of very large proteins to pIX
      can impair intracellular vector particle trafficking. Finally, we demonstrate
      that the geneti-chemical targeting technology is suitable for in vivo targeting
      to liver after intravenous injection. Our data provide significant insight into
      basic requirements for successful targeting of pIX-modified Ad vectors.

PMID- 18714310
TI  - Recombinant Newcastle disease virus as a vaccine vector for cancer therapy.
AB  - Naturally occurring strains of Newcastle disease virus (NDV) are currently being
      investigated in multiple clinical trials for oncolytic cancer therapy in the
      United States and abroad. We have previously reported, for the first time, the
      development of recombinant NDVs designed for enhanced cancer therapeutic
      efficacy. Specifically, we have shown that NDV engineered to express interleukin
      2 (IL-2) generates a robust therapeutic response associated with increased tumor
      specific T-cell infiltration after intratumoral administration in mice. We have
      now demonstrated that this therapeutic response is dependent on T cells and we
      have investigated the potential to focus the NDV-induced immune response toward a
      tumor-associated antigen (TAA) to enhance the inherent therapeutic efficacy of
      NDV further. We found that intratumoral treatments of tumor-bearing mice with
      recombinant NDV expressing a model TAA elicited an enhanced tumor-specific
      response, resulting in a significant increase in the number of complete tumor
      regressions compared with control NDV. Additionally, coadministration of NDV
      expressing a model TAA with NDV expressing IL-2 enhanced the TAA-directed
      response and led to more complete tumor regressions. Our results show that TAA
      directed immunotherapy by oncolytic recombinant NDV alone or in combination with
      IL-2 results in an enhanced therapeutic efficacy and warrant consideration in the
      development of cancer therapies based on the use of oncolytic NDV.

PMID- 18714311
TI  - Growth hormone-releasing hormone plasmid treatment by electroporation decreases
      offspring mortality over three pregnancies.
AB  - LifeTideSW5 is a growth hormone-releasing hormone (GHRH)-expressing plasmid
      delivered by intramuscular (IM) electroporation (EP), and the first therapeutic
      plasmid delivered by this physical method to be approved for use in food animals.
      Gestating sows (n = 997) were treated once with a single 5-mg GHRH-plasmid by EP
      or served as controls. Data on offspring from three parities subsequent to
      treatment were collected. No adverse effects related to treatment were noted.
      First parity post-treatment offspring from treated sows displayed a 2.93 kg (P <
      0.0001) increase in carcass weight (CW), 1.0 mm (P < 0.0001) less back-fat (P2),
      and a 27.0 g CW/day (P < 0.0001) increase in rate of gain (ROG) compared with
      controls. An increase of 21.6% was recorded in the number of offspring surviving.
      In the second and third parities post-treatment, offspring from treated females
      displayed higher number of born alive and total born number, and lower stillborn
      rates. Third parity offspring from treated sows displayed a 1.6 kg advantage in
      CW (P < 0.05), 1.0 mm less P2 (P < 0.05), and a 10.0 g CW/day benefit in ROG.
      Furthermore, offspring from treated females had a 19.04% lower post-wean loss
      rate. Overall, plasmid GHRH administration decreased morbidity and mortality in
      treated females and their offspring over three consecutive pregnancies.

PMID- 18714312
TI  - Preventing growth of brain tumors by creating a zone of resistance.
AB  - Glioblastoma multiforme (GBM) is a devastating form of brain cancer for which
      there is no effective treatment. Here, we report a novel approach to brain tumor
      therapy through genetic modification of normal brain cells to block tumor growth
      and effect tumor regression. Previous studies have focused on the use of vector
      based gene therapy for GBM by direct intratumoral injection with expression of
      therapeutic proteins by tumor cells themselves. However, as antitumor proteins
      are generally lethal to tumor cells, the therapeutic reservoir is rapidly
      depleted, allowing escape of residual tumor cells. Moreover, it has been
      difficult to achieve consistent transduction of these highly heterogeneous
      tumors. In our studies, we found that transduction of normal cells in the brain
      with an adeno-associated virus (AAV) vector encoding interferon-beta (IFN-beta)
      was sufficient to completely prevent tumor growth in orthotopic xenograft models
      of GBM, even in the contralateral hemisphere. In addition, complete eradication
      of established tumors was achieved through expression of IFN-beta by neurons
      using a neuronal-restricted promoter. To our knowledge this is the first direct
      demonstration of the efficacy of targeting gene delivery exclusively to normal
      brain cells for brain tumor therapy.

PMID- 18714314
TI  - Is this the drug or dose for you? Impact and consideration of ethnic factors in
      global drug development, regulatory review, and clinical practice.

PMID- 18714317
TI  - The critical path of warfarin dosing: finding an optimal dosing strategy using
      pharmacogenetics.

PMID- 18714318
TI  - Warfarin and pharmacogenomic testing: the case for restraint.

PMID- 18714319
TI  - Individual genomes instead of race for personalized medicine.
AB  - The cost of sequencing and genotyping is aggressively decreasing, enabling
      pervasive personalized genomic screening for drug reactions. Drug-metabolizing
      genes have been characterized sufficiently to enable practitioners to go beyond
      simplistic ethnic characterization and into the precisely targeted world of
      personal genomics. We examine six drug-metabolizing genes in J. Craig Venter and
      James Watson, two Caucasian men whose genomes were recently sequenced. Their
      genetic differences underscore the importance of personalized genomics over a
      race-based approach to medicine. To attain truly personalized medicine, the
      scientific community must aim to elucidate the genetic and environmental factors
      that contribute to drug reactions and not be satisfied with a simple race-based
      approach.

PMID- 18714320
TI  - What's needed for personalized therapy in smoking cessation.
AB  - It has long been known that smoking cessation is one of the most cost-effective
      public health opportunities available. The fact that some 22% of Americans
      smoke,(1) despite overwhelming evidence of the consequences, reflects in part the
      addictive aspects of smoking and the generally modest effectiveness of various
      strategies for quitting. Although one of the US Department of Health and Human
      Services goals for the year 2010 is universal coverage of smoking-cessation
      agents,(2) only about a third of payers currently cover the cost of such
      agents.(3) A major disincentive is that the return on investment has been modeled
      to take at least 5 years to reach the break-even point,(4,5) given the cost of
      the individual agents, the high recidivism rates, the timeline for influencing
      outcomes, and the relative ineffectiveness of studied agents in broad or
      untargeted populations. The article by Patterson et al.(6) in this issue
      intriguingly suggests that there might be a way to use smokers' phenotypes to
      determine before treatment initiation which smokers will respond to which
      therapy. This approach could greatly improve the overall effectiveness of smoking
      cessation agents and generate cost savings that might in turn have the effect of
      influencing more payers to cover these agents.

PMID- 18714321
TI  - How European regulators view foreign data in the approval process.
AB  - The regulation of medicines should be based on sound scientific principles, and
      where these are uncertain the regulator may have difficulties. Nowhere is this
      illustrated more clearly than in the debate over how clinical data obtained in
      one part of the world can be used for regulatory purposes elsewhere.

PMID- 18714325
TI  - Molecular mechanisms of L-DOPA-induced dyskinesia.
AB  - L-DOPA (L-3,4-dihydroxyphenylalanine) remains the most effective drug for the
      treatment of Parkinson's disease. However, chronic use causes dyskinesia, a
      complex motor phenomenon that consists of two components: the execution of
      involuntary movements in response to drug administration, and the 'priming'
      phenomenon that underlies these movements' establishment and persistence. A
      reinterpretation of recent data suggests that priming for dyskinesia results from
      nigral denervation and the loss of striatal dopamine input, which alters
      glutamatergic synaptic connectivity in the striatum. The subsequent response of
      the abnormal basal ganglia to dopaminergic drugs determines the manner and timing
      of dyskinesia expression. The combination of nigral denervation and drug
      treatment establishes inappropriate signalling between the motor cortex and the
      striatum, leading to persistent dyskinesia.

PMID- 18714326
TI  - Computational models of schizophrenia and dopamine modulation in the prefrontal
      cortex.
AB  - Computational neuroscience models can be used to understand the diminished
      stability and noisy neurodynamical behaviour of prefrontal cortex networks in
      schizophrenia. These neurodynamical properties can be captured by simulated
      neural networks with randomly spiking neurons that introduce noise into the
      system and produce trial-by-trial variation of postsynaptic potentials.
      Theoretical and experimental studies have aimed to understand schizophrenia in
      relation to noise and signal-to-noise ratio, which are promising concepts for
      understanding the symptoms that characterize this heterogeneous illness.
      Simulations of biologically realistic neural networks show how the functioning of
      NMDA (N-methyl-D-aspartate), GABA (gamma-aminobutyric acid) and dopamine
      receptors is connected to the concepts of noise and variability, and to related
      neurophysiological findings and clinical symptoms in schizophrenia.

PMID- 18714327
TI  - Applications of real-time fMRI.
AB  - For centuries people have aspired to understand and control the functions of the
      mind and brain. It has now become possible to image the functioning of the human
      brain in real time using functional MRI (fMRI), and thereby to access both sides
      of the mind-brain interface--subjective experience (that is, one's mind) and
      objective observations (that is, external, quantitative measurements of one's
      brain activity)--simultaneously. Developments in neuroimaging are now being
      translated into many new potential practical applications, including the reading
      of brain states, brain-computer interfaces, communicating with locked-in
      patients, lie detection, and learning control over brain activation to modulate
      cognition or even treat disease.

PMID- 18714328
TI  - By studying ageing, endocrinology stays young.

PMID- 18714329
TI  - Selection of antiresorptive or anabolic treatments for postmenopausal
      osteoporosis.
AB  - Osteoporosis is a common, chronic disease that can be treated effectively by
      pharmacological interventions. Antiosteoporotic drugs reduce fracture risk via
      different mechanisms of action. Available therapies are broadly distinguished
      into inhibitors of bone turnover, stimulators of bone formation, and therapies
      with as-yet unclear mechanisms of action. No direct comparison studies with
      fracture end points have yet been done, which makes selection of one drug over
      another difficult. Identification of individuals who might derive particular
      benefit from a specific therapy has been explored in post-hoc analyses of
      clinical studies with bisphosphonates and recombinant parathyroid hormone (PTH).
      Their findings showed that the efficacy of these therapies in reducing fracture
      risk was largely independent of the prevalent rates of bone turnover. Selection
      of a specific antiosteoporotic therapy should, therefore, be made according to
      the results of trials specifically designed to assess fracture risk, safety,
      tolerability, patient preference and cost-effectiveness rather than on
      characteristics specific to patients or the disease. Studies of sequential
      administration of PTH and bisphosphonates suggest advantages over single-therapy
      regimens, particularly in patients with severe disease. However, the optimum
      duration of PTH administration, as well as the efficacy of such regimens in
      reducing the risk of fractures, remain to be determined.

PMID- 18714330
TI  - Stimulation-induced increases of astrocytic oxidative metabolism in rats and
      humans investigated with 1-11C-acetate.
AB  - The purpose of this study was to investigate astrocytic oxidative metabolism
      using 1-(11)C-acetate. 1-(11)C-acetate kinetics were evaluated in the rat
      somatosensory cortex using a beta-scintillator during different manipulations
      (test-retest, infraorbital nerve stimulation, and administration of acetazolamide
      or dichloroacetate). In humans a visual activation paradigm was used and kinetics
      were measured with positron emission tomography. Data were analyzed using a one
      tissue compartment model. The following features supported the hypothesis that
      washout of radiolabel (k(2)) is because of (11)C-CO(2) and therefore related to
      oxygen consumption (CMRO(2)): (1) the onset of (11)C washout was delayed; (2)k(2)
      was not affected by acetazolamide-induced blood flow increase; (3)k(2)
      demonstrated a significant increase during stimulation in rats (from 0.014+/
      0.007 to 0.027+/-0.006 per minute) and humans (from 0.016+/-0.010 to 0.026+/
      0.006 per minute); and (4) dichloroacetate led to a substantial decrease of k(2).
      In the test-retest experiments K(1) and k(2) were very stable. In summary, 1
      (11)C-acetate seems a promising tracer to investigate astrocytic oxidative
      metabolism in vivo. If the washout rate indeed represents the production of (11)C
      CO(2), then its increase during stimulation would point to a substantially higher
      astrocytic oxidative metabolism during brain activation. However, the
      quantitative relationship between k(2) and CMRO(2) needs to be determined in
      future experiments.

PMID- 18714333
TI  - Regioselective Cleavage of 3,4-Epoxy Alcohols with Substituted Alkynylaluminum
      Reagents: Application to the Stereoselective Synthesis of Polypropionates.
AB  - The reaction of 3-O-substituted propynyl aluminum reagents with a TIPS-protected
      2,3-epoxy alcohol and several diastereomeric 2-methyl-3,4-epoxy alcohols offers a
      convenient synthetic approach for the subsequent preparation and epoxidation of
      allylic alcohols. The yields are low to moderate and the regioselectivity
      (internal vs external attack) similar to that of the standard diethylpropynyl
      aluminum reagent. The TMS-acetylide alane reagent gives improved yields and good
      regioselectivity, and constitutes the reagent of choice for the cleavage of the
      hindered epoxides. This attractive methodology is applied to the elaboration of
      two advanced polypropionate precursor fragments.

PMID- 18714331
TI  - Comparative neuroprotective effects of cyclosporin A and NIM811, a
      nonimmunosuppressive cyclosporin A analog, following traumatic brain injury.
AB  - Earlier experiments have shown that cyclosporin A (CsA) and its non-calcineurin
      inhibitory analog NIM811 attenuate mitochondrial dysfunction after experimental
      traumatic brain injury (TBI). Presently, we compared the neuroprotective effects
      of previously determined mitochondrial protective doses of CsA (20 mg/kg
      intraperitoneally) and NIM811 (10 mg/kg intraperitoneally) when administered at
      15 mins postinjury in preventing cytoskeletal (alpha-spectrin) degradation,
      neurodegeneration, and neurological dysfunction after severe (1.0 mm) controlled
      cortical impact (CCI) TBI in mice. In a first set of experiments, we analyzed
      calpain-mediated alpha-spectrin proteolysis at 24 h postinjury. Both NIM811 and
      CsA significantly attenuated the increased alpha-spectrin breakdown products
      observed in vehicle-treated animals (P<0.005). In a second set of experiments,
      treatment of animals with either NIM811 or CsA at 15 mins and again at 24 h
      postinjury attenuated motor function impairment at 48 h and 7 days (P<0.005) and
      neurodegeneration at 7 days postinjury (P<0.0001). Delayed administration of
      NIM811 out to 12 h was still able to significantly reduce alpha-spectrin
      degradation. These results show that the neuroprotective mechanism of CsA
      involves maintenance of mitochondrial integrity and that calcineurin inhibition
      plays little or no role because the non-calcineurin inhibitory analog, NIM811, is
      as effective as CsA.

PMID- 18714334
TI  - Fast homeostatic plasticity of inhibition via activity-dependent vesicular
      filling.
AB  - Synaptic activity in the central nervous system undergoes rapid state-dependent
      changes, requiring constant adaptation of the homeostasis between excitation and
      inhibition. The underlying mechanisms are, however, largely unclear. Chronic
      changes in network activity result in enhanced production of the inhibitory
      transmitter GABA, indicating that presynaptic GABA content is a variable
      parameter for homeostatic plasticity. Here we tested whether such changes in
      inhibitory transmitter content do also occur at the fast time scale required to
      ensure inhibition-excitation-homeostasis in dynamic cortical networks. We found
      that intense stimulation of afferent fibers in the CA1 region of mouse
      hippocampal slices yielded a rapid and lasting increase in quantal size of
      miniature inhibitory postsynaptic currents. This potentiation was mediated by the
      uptake of GABA and glutamate into presynaptic endings of inhibitory interneurons
      (the latter serving as precursor for the synthesis of GABA). Thus, enhanced
      release of inhibitory and excitatory transmitters from active networks leads to
      enhanced presynaptic GABA content. Thereby, inhibitory efficacy follows local
      neuronal activity, constituting a negative feedback loop and providing a
      mechanism for rapid homeostatic scaling in cortical circuits.

PMID- 18714335
TI  - HIV seroprevalence among tuberculosis patients in India, 2006-2007.
AB  - BACKGROUND: Little information exists regarding the burden of HIV among
      tuberculosis patients in India, and no population-based surveys have been
      previously reported. A community-based HIV prevalence survey was conducted among
      tuberculosis patients treated by the national tuberculosis control programme to
      evaluate the HIV prevalence among tuberculosis patients in India.
      METHODOLOGY/PRINCIPAL FINDINGS: Fifteen districts (total population: 40.2
      million) across 8 states were stratified by HIV prevalence in antenatal clinic
      HIV surveillance sites and randomly selected. From December 2006 to May 2007,
      remnant serum was collected from patients' clinical specimens taken after 2
      months of anti-tuberculosis treatment and subjected to anonymous, unlinked HIV
      testing. Specimens were obtained and successfully tested for 5,995 (73%) of 8,217
      tuberculosis patients eligible for the survey. HIV prevalence ranged widely among
      the 15 surveyed districts, from 1% in Koch Bihar, West Bengal, to 13.8% in
      Guntur, Andhra Pradesh. HIV infection was 1.3 times more likely among male TB
      patients than among female patients. Relative to smear-positive tuberculosis, HIV
      infection was 1.4 times more likely among smear-negative patients and 1.3 times
      more likely among extrapulmonary patients. In 4 higher-HIV prevalence districts,
      which had been previously surveyed in 2005-2006, no significant change in HIV
      prevalence was detected. CONCLUSIONS: The burden of HIV among tuberculosis
      patients varies widely in India. Programme efforts to implement comprehensive TB
      HIV services should be targeted to areas with the highest HIV burden.
      Surveillance through routine reporting or special surveys is necessary to detect
      areas requiring intensification of TB-HIV collaborative activities.

PMID- 18714336
TI  - I-II loop structural determinants in the gating and surface expression of low
      voltage-activated calcium channels.
AB  - The intracellular loops that interlink the four transmembrane domains of Ca(2+)-
      and Na(+)-channels (Ca(v), Na(v)) have critical roles in numerous forms of
      channel regulation. In particular, the intracellular loop that joins repeats I
      and II (I-II loop) in high voltage-activated (HVA) Ca(2+) channels possesses the
      binding site for Ca(v)beta subunits and plays significant roles in channel
      function, including trafficking the alpha(1) subunits of HVA channels to the
      plasma membrane and channel gating. Although there is considerable divergence in
      the primary sequence of the I-II loop of Ca(v)1/Ca(v)2 HVA channels and Ca(v)3
      LVA/T-type channels, evidence for a regulatory role of the I-II loop in T-channel
      function has recently emerged for Ca(v)3.2 channels. In order to provide a
      comprehensive view of the role this intracellular region may play in the gating
      and surface expression in Ca(v)3 channels, we have performed a structure-function
      analysis of the I-II loop in Ca(v)3.1 and Ca(v)3.3 channels using selective
      deletion mutants. Here we show the first 60 amino acids of the loop (post IS6)
      are involved in Ca(v)3.1 and Ca(v)3.3 channel gating and kinetics, which
      establishes a conserved property of this locus for all Ca(v)3 channels. In
      contrast to findings in Ca(v)3.2, deletion of the central region of the I-II loop
      in Ca(v)3.1 and Ca(v)3.3 yielded a modest increase (+30%) and a reduction (-30%)
      in current density and surface expression, respectively. These experiments enrich
      our understanding of the structural determinants involved in Ca(v)3 function by
      highlighting the unique role played by the intracellular I-II loop in Ca(v)3.2
      channel trafficking, and illustrating the prominent role of the gating brake in
      setting the slow and distinctive slow activation kinetics of Ca(v)3.3.

PMID- 18714337
TI  - Identification of functional networks of estrogen- and c-Myc-responsive genes and
      their relationship to response to tamoxifen therapy in breast cancer.
AB  - BACKGROUND: Estrogen is a pivotal regulator of cell proliferation in the normal
      breast and breast cancer. Endocrine therapies targeting the estrogen receptor are
      effective in breast cancer, but their success is limited by intrinsic and
      acquired resistance. METHODOLOGY/PRINCIPAL FINDINGS: With the goal of gaining
      mechanistic insights into estrogen action and endocrine resistance, we classified
      estrogen-regulated genes by function, and determined the relationship between
      functionally-related genesets and the response to tamoxifen in breast cancer
      patients. Estrogen-responsive genes were identified by transcript profiling of
      MCF-7 breast cancer cells. Pathway analysis based on functional annotation of
      these estrogen-regulated genes identified gene signatures with known or predicted
      roles in cell cycle control, cell growth (i.e. ribosome biogenesis and protein
      synthesis), cell death/survival signaling and transcriptional regulation. Since
      inducible expression of c-Myc in antiestrogen-arrested cells can recapitulate
      many of the effects of estrogen on molecular endpoints related to cell cycle
      progression, the estrogen-regulated genes that were also targets of c-Myc were
      identified using cells inducibly expressing c-Myc. Selected genes classified as
      estrogen and c-Myc targets displayed similar levels of regulation by estrogen and
      c-Myc and were not estrogen-regulated in the presence of siMyc. Genes regulated
      by c-Myc accounted for 50% of all acutely estrogen-regulated genes but comprised
      85% (110/129 genes) in the cell growth signature. siRNA-mediated inhibition of c
      Myc induction impaired estrogen regulation of ribosome biogenesis and protein
      synthesis, consistent with the prediction that estrogen regulates cell growth
      principally via c-Myc. The 'cell cycle', 'cell growth' and 'cell death' gene
      signatures each identified patients with an attenuated response in a cohort of
      246 tamoxifen-treated patients. In multivariate analysis the cell death signature
      was predictive independent of the cell cycle and cell growth signatures.
      CONCLUSIONS/SIGNIFICANCE: These functionally-based gene signatures can stratify
      patients treated with tamoxifen into groups with differing outcome, and
      potentially identify distinct mechanisms of tamoxifen resistance.

PMID- 18714338
TI  - T cells' immunological synapses induce polarization of brain astrocytes in vivo
      and in vitro: a novel astrocyte response mechanism to cellular injury.
AB  - BACKGROUND: Astrocytes usually respond to trauma, stroke, or neurodegeneration by
      undergoing cellular hypertrophy, yet, their response to a specific immune attack
      by T cells is poorly understood. Effector T cells establish specific contacts
      with target cells, known as immunological synapses, during clearance of virally
      infected cells from the brain. Immunological synapses mediate intercellular
      communication between T cells and target cells, both in vitro and in vivo. How
      target virally infected astrocytes respond to the formation of immunological
      synapses established by effector T cells is unknown. FINDINGS: Herein we
      demonstrate that, as a consequence of T cell attack, infected astrocytes undergo
      dramatic morphological changes. From normally multipolar cells, they become
      unipolar, extending a major protrusion towards the immunological synapse formed
      by the effector T cells, and withdrawing most of their finer processes. Thus,
      target astrocytes become polarized towards the contacting T cells. The MTOC, the
      organizer of cell polarity, is localized to the base of the protrusion, and Golgi
      stacks are distributed throughout the protrusion, reaching distally towards the
      immunological synapse. Thus, rather than causing astrocyte hypertrophy, antiviral
      T cells cause a major structural reorganization of target virally infected
      astrocytes. CONCLUSIONS: Astrocyte polarization, as opposed to hypertrophy, in
      response to T cell attack may be due to T cells providing a very focused attack,
      and thus, astrocytes responding in a polarized manner. A similar polarization of
      Golgi stacks towards contacting T cells was also detected using an in vitro
      allogeneic model. Thus, different T cells are able to induce polarization of
      target astrocytes. Polarization of target astrocytes in response to immunological
      synapses may play an important role in regulating the outcome of the response of
      astrocytes to attacking effector T cells, whether during antiviral (e.g. infected
      during HIV, HTLV-1, HSV-1 or LCMV infection), anti-transplant, autoimmune, or
      anti-tumor immune responses in vivo and in vitro.

PMID- 18714339
TI  - Lamin A/C is a risk biomarker in colorectal cancer.
AB  - BACKGROUND: A-type lamins are type V intermediate filament proteins encoded by
      the gene LMNA. Mutations in LMNA give rise to diverse degenerative diseases
      related to premature ageing. A-type lamins also influence the activity of the
      Retinoblastoma protein (pRb) and oncogenes such a beta-catenin. Consequently, it
      has been speculated that expression of A-type lamins may also influence tumour
      progression. METHODOLOGY/PRINCIPAL FINDINGS: An archive of colorectal cancer
      (CRC) and normal colon tissue was screened for expression of A-type lamins. We
      used the Cox proportional hazard ratio (HR) method to investigate patient
      survival. Using CRC cell lines we investigated the effects of lamin A expression
      on other genes by RT-PCR; on cell growth by FACS analysis; and on invasiveness by
      cell migration assays and siRNA knockdown of targeted genes. We found that lamin
      A is expressed in colonic stem cells and that patients with A-type lamin
      expressing tumours have significantly worse prognosis than patients with A-type
      lamin negative tumours (HR = 1.85, p = 0.005). To understand this finding, we
      established a model system based upon expression of GFP-lamin A in CRC cells. We
      found that expression of GFP-lamin A in these cells did not affect cell
      proliferation but did promote greatly increased cell motility and invasiveness.
      The reason for this increased invasiveness was that expression of lamin A
      promoted up-regulation of the actin bundling protein T-plastin, leading to down
      regulation of the cell adhesion molecule E-cadherin. CONCLUSIONS: Expression of A
      type lamins increases the risk of death from CRC because its presence gives rise
      to increased invasiveness and potentially a more stem cell-like phenotype. This
      report directly links A-type lamin expression to tumour progression and raises
      the profile of LMNA from one implicated in multiple but rare genetic conditions
      to a gene involved in one of the commonest diseases in the Western World.

PMID- 18714340
TI  - Freeze-dried somatic cells direct embryonic development after nuclear transfer.
AB  - The natural capacity of simple organisms to survive in a dehydrated state has
      long been exploited by man, with lyophylization the method of choice for the long
      term storage of bacterial and yeast cells. More recently, attempts have been made
      to apply this procedure to the long term storage of blood cells. However, despite
      significant progress, practical application in a clinical setting is still some
      way off. Conversely, to date there are no reports of attempts to lyophilize
      nucleated somatic cells for possible downstream applications. Here we demonstrate
      that lyophilised somatic cells stored for 3 years at room temperature are able to
      direct embryonic development following injection into enucleated oocytes. These
      remarkable results demonstrate that alternative systems for the long-term storage
      of cell lines are now possible, and open unprecedented opportunities in the
      fields of biomedicine and for conservation strategies.

PMID- 18714341
TI  - The correction of eye blink artefacts in the EEG: a comparison of two prominent
      methods.
AB  - BACKGROUND: The study investigated the residual impact of eyeblinks on the
      electroencephalogram (EEG) after application of different correction procedures,
      namely a regression method (eye movement correction procedure, EMCP) and a
      component based method (Independent Component Analysis, ICA).
      METHODOLOGY/PRINCIPLE FINDINGS: Real and simulated data were investigated with
      respect to blink-related potentials and the residual mutual information of
      uncorrected vertical electrooculogram (EOG) and corrected EEG, which is a measure
      of residual EOG contribution to the EEG. The results reveal an occipital
      positivity that peaks at about 250 ms after the maximum blink excursion following
      application of either correction procedure. This positivity was not observable in
      the simulated data. Mutual information of vertical EOG and EEG depended on the
      applied regression procedure. In addition, different correction results were
      obtained for real and simulated data. ICA yielded almost perfect correction in
      all conditions. However, under certain conditions EMCP yielded comparable results
      to the ICA approach. CONCLUSION: In conclusion, for EMCP the quality of
      correction depended on the EMCP variant used and the structure of the data,
      whereas ICA always yielded almost perfect correction. However, its disadvantage
      is the much more complex data processing, and that it requires a suitable amount
      of data.

PMID- 18714342
TI  - Stochastic and regulatory role of chromatin silencing in genomic response to
      environmental changes.
AB  - Phenotypic diversity and fidelity can be balanced by controlling stochastic
      molecular mechanisms. Epigenetic silencing is one that has a critical role in
      stress response. Here we show that in yeast, incomplete silencing increases
      stochastic noise in gene expression, probably owing to unstable chromatin
      structure. Telomere position effect is suggested as one mechanism. Expression
      diversity in a population achieved in this way may render a subset of cells to
      readily respond to various acute stresses. By contrast, strong silencing tends to
      suppress noisy expression of genes, in particular those involved in life cycle
      control. In this regime, chromatin may act as a noise filter for precisely
      regulated responses to environmental signals that induce huge phenotypic changes
      such as a cell fate transition. These results propose modulation of chromatin
      stability as an important determinant of environmental adaptation and cellular
      differentiation.

PMID- 18714343
TI  - Resource competition triggers the co-evolution of long tongues and deep corolla
      tubes.
AB  - BACKGROUND: It is normally thought that deep corolla tubes evolve when a plant's
      successful reproduction is contingent on having a corolla tube longer than the
      tongue of the flower's pollinators, and that pollinators evolve ever-longer
      tongues because individuals with longer tongues can obtain more nectar from
      flowers. A recent model shows that, in the presence of pollinators with long and
      short tongues that experience resource competition, coexisting plant species can
      diverge in corolla-tube depth, because this increases the proportion of pollen
      grains that lands on co-specific flowers. METHODOLOGY/PRINCIPAL FINDINGS: We have
      extended the model to study whether resource competition can trigger the co
      evolution of tongue length and corolla-tube depth. Starting with two plant and
      two pollinator species, all of them having the same distribution of tongue length
      or corolla-tube depth, we show that variability in corolla-tube depth leads to
      divergence in tongue length, provided that increasing tongue length is not
      equally costly for both species. Once the two pollinator species differ in tongue
      length, divergence in corolla-tube depth between the two plant species ensues.
      CONCLUSIONS/SIGNIFICANCE: Co-evolution between tongue length and corolla-tube
      depth is a robust outcome of the model, obtained for a wide range of parameter
      values, but it requires that tongue elongation is substantially easier for one
      pollinator species than for the other, that pollinators follow a near-optimal
      foraging strategy, that pollinators experience competition for resources and that
      plants experience pollination limitation.

PMID- 18714344
TI  - Elevated peripheral visfatin levels in narcoleptic patients.
AB  - OBJECTIVE: Narcolepsy is a severe sleep disorder that is characterized by
      excessive daytime sleepiness, cataplexies and a tendency towards obesity. Recent
      discoveries indicate that the major pathophysiology is a loss of hypocretin
      (orexin) producing neurons due to immunologically mediated degeneration. Visfatin
      is a recently described proinflammatory adipokine. It is identical to the immune
      modulating pre-B-cell colony enhancing factor (PBEF). Our study examines the
      hypothesis that visfatin levels are altered in narcoleptic patients. METHODS: For
      the analysis, a total of n = 54 patients (n = 18 males and n = 36 females) with
      the diagnosis of narcolepsy according to DSM-IV and the International
      Classification of Sleep Disorders were examined (BMI mean 30.3+/-5.5, age mean
      52.5+/-16.1 years). As a control group 39 unrelated (n = 12 males and n = 27
      females) healthy volunteers with no sleep disorder according to DSM-IV were
      included (BMI mean 28.5+/-4.6, age mean 51.1+/-13.6 years). Peripheral visfatin
      levels were measured using a commercial enzyme immunoassay kit with a measurement
      range from 0.1-1000 ng/ml. Narcolepsy symptoms, severity and frequency of
      symptoms as well as the total duration of various aspects of the symptomatology
      were assessed by unstructured and structured clinical interviews in including the
      Stanford Center for Narcolepsy Sleep Inventory. RESULTS: Circulating visfatin was
      found to be significantly increased in HLA DR2 positive narcoleptic patients
      compared to controls. CONCLUSION: Taken together, our results add to the evidence
      of disturbed immunological regulation in patients with narcolepsy.

PMID- 18714346
TI  - Adaptive melanin response of the soil fungus Aspergillus niger to UV radiation
      stress at "Evolution Canyon", Mount Carmel, Israel.
AB  - BACKGROUND: Adaptation is an evolutionary process in which traits in a population
      are tailored by natural selection to better meet the challenges presented by the
      local environment. The major discussion relating to natural selection concerns
      the portraying of the cause and effect relationship between a presumably adaptive
      trait and selection agents generating it. Therefore, it is necessary to identify
      trait(s) that evolve in direct response to selection, enhancing the organism's
      fitness. "Evolution Canyon" (EC) in Israel mirrors a microcosmic evolutionary
      system across life and is ideal to study natural selection and local adaptation
      under sharply, microclimatically divergent environments. The south-facing,
      tropical, sunny and xeric "African" slope (AS) receives 200%-800% higher solar
      radiation than the north-facing, temperate, shady and mesic "European" slope
      (ES), 200 meters apart. Thus, solar ultraviolet radiation (UVR) is a major
      selection agent in EC influencing the organism-environment interaction. Melanin
      is a trait postulated to have evolved for UV-screening in microorganisms. Here we
      investigate the cause and effect relationship between differential UVR on the
      opposing slopes of EC and the conidial melanin concentration of the filamentous
      soil fungus Aspergillus niger. We test the working hypothesis that the AS strains
      exhibit higher melanin content than strains from the ES resulting in higher UV
      resistance. METHODOLOGY/PRINCIPAL FINDINGS: We measured conidial melanin
      concentration of 80 strains from the EC using a spectrophotometer. The results
      indicated that mean conidial melanin concentration of AS strains were threefold
      higher than ES strains and the former resisted UVA irradiation better than the
      latter. Comparisons of melanin in the conidia of A. niger strains from sunny and
      shady microniches on the predominantly sunny AS and predominantly shady ES
      indicated that shady conditions on the AS have no influence on the selection on
      melanin; in contrast, the sunny strains from the ES displayed higher melanin
      concentrations. CONCLUSIONS/SIGNIFICANCE: We conclude that melanin in A. niger is
      an adaptive trait against UVR generated by natural selection.

PMID- 18714345
TI  - HIV replication enhances production of free fatty acids, low density lipoproteins
      and many key proteins involved in lipid metabolism: a proteomics study.
AB  - BACKGROUND: HIV-infected patients develop multiple metabolic abnormalities
      including insulin resistance, lipodystrophy and dyslipidemia. Although
      progression of these disorders has been associated with the use of various
      protease inhibitors and other antiretroviral drugs, HIV-infected individuals who
      have not received these treatments also develop lipid abnormalities albeit to a
      lesser extent. How HIV alters lipid metabolism in an infected cell and what
      molecular changes are affected through protein interaction pathways are not well
      understood. RESULTS: Since many genetic, epigenetic, dietary and other factors
      influence lipid metabolism in vivo, we have chosen to study genome-wide changes
      in the proteomes of a human T-cell line before and after HIV infection in order
      to circumvent computational problems associated with multiple variables. Four
      separate experiments were conducted including one that compared 14 different time
      points over a period of >3 months. By subtractive analyses of protein profiles
      overtime, several hundred differentially expressed proteins were identified in
      HIV-infected cells by mass spectrometry and each protein was scrutinized for its
      biological functions by using various bioinformatics programs. Herein, we report
      18 HIV-modulated proteins and their interaction pathways that enhance fatty acid
      synthesis, increase low density lipoproteins (triglycerides), dysregulate lipid
      transport, oxidize lipids, and alter cellular lipid metabolism. CONCLUSIONS: We
      conclude that HIV replication alone (i.e. without any influence of antiviral
      drugs, or other human genetic factors), can induce novel cellular enzymes and
      proteins that are significantly associated with biologically relevant processes
      involved in lipid synthesis, transport and metabolism (p = <0.0002-0.01).
      Translational and clinical studies on the newly discovered proteins may now shed
      light on how some of these proteins may be useful for early diagnosis of
      individuals who might be at high risk for developing lipid-related disorders. The
      target proteins could then be used for future studies in the development of
      inhibitors for preventing lipid-metabolic anomalies. This is the first direct
      evidence that HIV-modulates production of proteins that are significantly
      involved in disrupting the normal lipid-metabolic pathways.

PMID- 18714347
TI  - Generation and validation of a Shewanella oneidensis MR-1 clone set for protein
      expression and phage display.
AB  - A comprehensive gene collection for S. oneidensis was constructed using the
      lambda recombinase (Gateway) cloning system. A total of 3584 individual ORFs
      (85%) have been successfully cloned into the entry plasmids. To validate the use
      of the clone set, three sets of ORFs were examined within three different
      destination vectors constructed in this study. Success rates for heterologous
      protein expression of S. oneidensis His- or His/GST-tagged proteins in E. coli
      were approximately 70%. The ArcA and NarP transcription factor proteins were
      tested in an in vitro binding assay to demonstrate that functional proteins can
      be successfully produced using the clone set. Further functional validation of
      the clone set was obtained from phage display experiments in which a phage
      encoding thioredoxin was successfully isolated from a pool of 80 different clones
      after three rounds of biopanning using immobilized anti-thioredoxin antibody as a
      target. This clone set complements existing genomic (e.g., whole-genome
      microarray) and other proteomic tools (e.g., mass spectrometry-based proteomic
      analysis), and facilitates a wide variety of integrated studies, including
      protein expression, purification, and functional analyses of proteins both in
      vivo and in vitro.

PMID- 18714348
TI  - Prognostic breast cancer signature identified from 3D culture model accurately
      predicts clinical outcome across independent datasets.
AB  - BACKGROUND: One of the major tenets in breast cancer research is that early
      detection is vital for patient survival by increasing treatment options. To that
      end, we have previously used a novel unsupervised approach to identify a set of
      genes whose expression predicts prognosis of breast cancer patients. The
      predictive genes were selected in a well-defined three dimensional (3D) cell
      culture model of non-malignant human mammary epithelial cell morphogenesis as
      down-regulated during breast epithelial cell acinar formation and cell cycle
      arrest. Here we examine the ability of this gene signature (3D-signature) to
      predict prognosis in three independent breast cancer microarray datasets having
      295, 286, and 118 samples, respectively. METHODS AND FINDINGS: Our results show
      that the 3D-signature accurately predicts prognosis in three unrelated patient
      datasets. At 10 years, the probability of positive outcome was 52, 51, and 47
      percent in the group with a poor-prognosis signature and 91, 75, and 71 percent
      in the group with a good-prognosis signature for the three datasets, respectively
      (Kaplan-Meier survival analysis, p<0.05). Hazard ratios for poor outcome were 5.5
      (95% CI 3.0 to 12.2, p<0.0001), 2.4 (95% CI 1.6 to 3.6, p<0.0001) and 1.9 (95% CI
      1.1 to 3.2, p = 0.016) and remained significant for the two larger datasets when
      corrected for estrogen receptor (ER) status. Hence the 3D-signature accurately
      predicts breast cancer outcome in both ER-positive and ER-negative tumors, though
      individual genes differed in their prognostic ability in the two subtypes. Genes
      that were prognostic in ER+ patients are AURKA, CEP55, RRM2, EPHA2, FGFBP1, and
      VRK1, while genes prognostic in ER- patients include ACTB, FOXM1 and SERPINE2
      (Kaplan-Meier p<0.05). Multivariable Cox regression analysis in the largest
      dataset showed that the 3D-signature was a strong independent factor in
      predicting breast cancer outcome. CONCLUSIONS: The 3D-signature accurately
      predicts breast cancer outcome across multiple datasets and holds prognostic
      value for both ER-positive and ER-negative breast cancer. The signature was
      selected using a novel biological approach and hence holds promise to represent
      the key biological processes of breast cancer.

PMID- 18714349
TI  - DnaC inactivation in Escherichia coli K-12 induces the SOS response and
      expression of nucleotide biosynthesis genes.
AB  - BACKGROUND: Initiation of chromosome replication in E. coli requires the DnaA and
      DnaC proteins and conditionally-lethal dnaA and dnaC mutants are often used to
      synchronize cell populations. METHODOLOGY/PRINCIPAL FINDINGS: DNA microarrays
      were used to measure mRNA steady-state levels in initiation-deficient dnaA46 and
      dnaC2 bacteria at permissive and non-permissive temperatures and their expression
      profiles were compared to MG1655 wildtype cells. For both mutants there was
      altered expression of genes involved in nucleotide biosynthesis at the non
      permissive temperature. Transcription of the dnaA and dnaC genes was increased at
      the non-permissive temperature in the respective mutant strains indicating auto
      regulation of both genes. Induction of the SOS regulon was observed in dnaC2
      cells at 38 degrees C and 42 degrees C. Flow cytometric analysis revealed that
      dnaC2 mutant cells at non-permissive temperature had completed the early stages
      of chromosome replication initiation. CONCLUSION/SIGNIFICANCE: We suggest that in
      dnaC2 cells the SOS response is triggered by persistent open-complex formation at
      oriC and/or by arrested forks that require DnaC for replication restart.

PMID- 18714350
TI  - Matched filters, mate choice and the evolution of sexually selected traits.
AB  - BACKGROUND: Fundamental for understanding the evolution of communication systems
      is both the variation in a signal and how this affects the behavior of receivers,
      as well as variation in preference functions of receivers, and how this affects
      the variability of the signal. However, individual differences in female
      preference functions and their proximate causation have rarely been studied.
      METHODOLOGY/PRINCIPAL FINDINGS: Calling songs of male field crickets represent
      secondary sexual characters and are subject to sexual selection by female choice.
      Following predictions from the "matched filter hypothesis" we studied the tuning
      of an identified interneuron in a field cricket, known for its function in
      phonotaxis, and correlated this with the preference of the same females in two
      choice trials. Females vary in their neuronal frequency tuning, which strongly
      predicts the preference in a choice situation between two songs differing in
      carrier frequency. A second "matched filter" exists in directional hearing, where
      reliable cues for sound localization occur only in a narrow frequency range.
      There is a strong correlation between the directional tuning and the behavioural
      preference in no-choice tests. This second "matched filter" also varies widely in
      females, and surprisingly, differs on average by 400 Hz from the neuronal
      frequency tuning. CONCLUSIONS/SIGNIFICANCE: Our findings on the mismatch of the
      two "matched filters" would suggest that the difference in these two filters
      appears to be caused by their evolutionary history, and the different trade-offs
      which exist between sound emission, transmission and detection, as well as
      directional hearing under specific ecological settings. The mismatched filter
      situation may ultimately explain the maintenance of considerable variation in the
      carrier frequency of the male signal despite stabilizing selection.

PMID- 18714351
TI  - Habitat-specific population growth of a farmland bird.
AB  - BACKGROUND: To assess population persistence of species living in heterogeneous
      landscapes, the effects of habitat on reproduction and survival have to be
      investigated. METHODOLOGY/PRINCIPAL FINDINGS: We used a matrix population model
      to estimate habitat-specific population growth rates for a population of northern
      wheatears Oenanthe oenanthe breeding in farmland consisting of a mosaic of
      distinct habitat (land use) types. Based on extensive long-term data on
      reproduction and survival, habitats characterised by tall field layers (spring-
      and autumn-sown crop fields, ungrazed grasslands) displayed negative stochastic
      population growth rates (log lambda(s): -0.332, -0.429, -0.168, respectively),
      that were markedly lower than growth rates of habitats characterised by
      permanently short field layers (pastures grazed by cattle or horses, and
      farmyards, log lambda(s): -0.056, +0.081, -0.059). Although habitats differed
      with respect to reproductive performance, differences in habitat-specific
      population growth were largely due to differences in adult and first-year
      survival rates, as shown by a life table response experiment (LTRE).
      CONCLUSIONS/SIGNIFICANCE: Our results show that estimation of survival rates is
      important for realistic assessments of habitat quality. Results also indicate
      that grazed grasslands and farmyards may act as source habitats, whereas crop
      fields and ungrazed grasslands with tall field layers may act as sink habitats.
      We suggest that the strong decline of northern wheatears in Swedish farmland may
      be linked to the corresponding observed loss of high quality breeding habitat,
      i.e. grazed semi-natural grasslands.

PMID- 18714352
TI  - Influence of prior influenza vaccination on antibody and B-cell responses.
AB  - Currently two vaccines, trivalent inactivated influenza vaccine (TIV) and live
      attenuated influenza vaccine (LAIV), are licensed in the USA. Despite previous
      studies on immune responses induced by these two vaccines, a comparative study of
      the influence of prior influenza vaccination on serum antibody and B-cell
      responses to new LAIV or TIV vaccination has not been reported. During the 2005/6
      influenza season, we quantified the serum antibody and B-cell responses to LAIV
      or TIV in adults with differing influenza vaccination histories in the prior
      year: LAIV, TIV, or neither. Blood samples were collected on days 0, 7-9 and 21
      35 after immunization and used for serum HAI assay and B-cell assays. Total and
      influenza-specific circulating IgG and IgA antibody secreting cells (ASC) in PBMC
      were detected by direct ELISPOT assay. Memory B cells were also tested by ELISPOT
      after polyclonal stimulation of PBMC in vitro. Serum antibody, effector, and
      memory B-cell responses were greater in TIV recipients than LAIV recipients.
      Prior year TIV recipients had significantly higher baseline HAI titers, but lower
      HAI response after vaccination with either TIV or LAIV, and lower IgA ASC
      response after vaccination with TIV than prior year LAIV or no vaccination
      recipients. Lower levels of baseline HAI titer were associated with a greater
      fold-increase of HAI titer and ASC number after vaccination, which also differed
      by type of vaccine. Our findings suggest that the type of vaccine received in the
      prior year affects the serum antibody and the B-cell responses to subsequent
      vaccination. In particular, prior year TIV vaccination is associated with
      sustained higher HAI titer one year later but lower antibody response to new LAIV
      or TIV vaccination, and a lower effector B-cell response to new TIV but not LAIV
      vaccination.

PMID- 18714353
TI  - The silkworm (Bombyx mori) microRNAs and their expressions in multiple
      developmental stages.
AB  - BACKGROUND: MicroRNAs (miRNAs) play crucial roles in various physiological
      processes through post-transcriptional regulation of gene expressions and are
      involved in development, metabolism, and many other important molecular
      mechanisms and cellular processes. The Bombyx mori genome sequence provides
      opportunities for a thorough survey for miRNAs as well as comparative analyses
      with other sequenced insect species. METHODOLOGY/PRINCIPAL FINDINGS: We
      identified 114 non-redundant conserved miRNAs and 148 novel putative miRNAs from
      the B. mori genome with an elaborate computational protocol. We also sequenced
      6,720 clones from 14 developmental stage-specific small RNA libraries in which we
      identified 35 unique miRNAs containing 21 conserved miRNAs (including 17
      predicted miRNAs) and 14 novel miRNAs (including 11 predicted novel miRNAs).
      Among the 114 conserved miRNAs, we found six pairs of clusters evolutionarily
      conserved cross insect lineages. Our observations on length heterogeneity at 5'
      and/or 3' ends of nine miRNAs between cloned and predicted sequences, and three
      mature forms deriving from the same arm of putative pre-miRNAs suggest a
      mechanism by which miRNAs gain new functions. Analyzing development-related
      miRNAs expression at 14 developmental stages based on clone-sampling and stem
      loop RT PCR, we discovered an unusual abundance of 33 sequences representing 12
      different miRNAs and sharply fluctuated expression of miRNAs at larva-molting
      stage. The potential functions of several stage-biased miRNAs were also analyzed
      in combination with predicted target genes and silkworm's phenotypic traits; our
      results indicated that miRNAs may play key regulatory roles in specific
      developmental stages in the silkworm, such as ecdysis. CONCLUSIONS/SIGNIFICANCE:
      Taking a combined approach, we identified 118 conserved miRNAs and 151 novel
      miRNA candidates from the B. mori genome sequence. Our expression analyses by
      sampling miRNAs and real-time PCR over multiple developmental stages allowed us
      to pinpoint molting stages as hotspots of miRNA expression both in sorts and
      quantities. Based on the analysis of target genes, we hypothesized that miRNAs
      regulate development through a particular emphasis on complex stages rather than
      general regulatory mechanisms.

PMID- 18714355
TI  - Phase shift from a coral to a corallimorph-dominated reef associated with a
      shipwreck on Palmyra atoll.
AB  - Coral reefs can undergo relatively rapid changes in the dominant biota, a
      phenomenon referred to as phase shift. Various reasons have been proposed to
      explain this phenomenon including increased human disturbance, pollution, or
      changes in coral reef biota that serve a major ecological function such as
      depletion of grazers. However, pinpointing the actual factors potentially
      responsible can be problematic. Here we show a phase shift from coral to the
      corallimorpharian Rhodactis howesii associated with a long line vessel that
      wrecked in 1991 on an isolated atoll (Palmyra) in the central Pacific Ocean. We
      documented high densities of R. howesii near the ship that progressively
      decreased with distance from the ship whereas R. howesii were rare to absent in
      other parts of the atoll. We also confirmed high densities of R. howesii around
      several buoys recently installed on the atoll in 2001. This is the first time
      that a phase shift on a coral reef has been unambiguously associated with man
      made structures. This association was made, in part, because of the remoteness of
      Palmyra and its recent history of minimal human habitation or impact. Phase
      shifts can have long-term negative ramification for coral reefs, and eradication
      of organisms responsible for phase shifts in marine ecosystems can be difficult,
      particularly if such organisms cover a large area. The extensive R. howesii
      invasion and subsequent loss of coral reef habitat at Palmyra also highlights the
      importance of rapid removal of shipwrecks on corals reefs to mitigate the
      potential of reef overgrowth by invasives.

PMID- 18714354
TI  - The Rho-Rock-Myosin signaling axis determines cell-cell integrity of self
      renewing pluripotent stem cells.
AB  - BACKGROUND: Embryonic stem (ES) cells self-renew as coherent colonies in which
      cells maintain tight cell-cell contact. Although intercellular communications are
      essential to establish the basis of cell-specific identity, molecular mechanisms
      underlying intrinsic cell-cell interactions in ES cells at the signaling level
      remain underexplored. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that
      endogenous Rho signaling is required for the maintenance of cell-cell contacts in
      ES cells. siRNA-mediated loss of function experiments demonstrated that Rock, a
      major effector kinase downstream of Rho, played a key role in the formation of
      cell-cell junctional assemblies through regulation of myosin II by controlling a
      myosin light chain phosphatase. Chemical engineering of this signaling axis by a
      Rock-specific inhibitor revealed that cell-cell adhesion was reversibly
      controllable and dispensable for self-renewal of mouse ES cells as confirmed by
      chimera assay. Furthermore, a novel culture system combining a single synthetic
      matrix, defined medium, and the Rock inhibitor fully warranted human ES cell self
      renewal independent of animal-derived matrices, tight cell contacts, or
      fibroblastic niche-forming cells as determined by teratoma formation assay.
      CONCLUSIONS/SIGNIFICANCE: These findings demonstrate an essential role of the Rho
      Rock-Myosin signaling axis for the regulation of basic cell-cell communications
      in both mouse and human ES cells, and would contribute to advance in medically
      compatible xeno-free environments for human pluripotent stem cells.

PMID- 18714356
TI  - OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with
      frequently epigenetic inactivation.
AB  - BACKGROUND: Identification of tumor suppressor genes (TSGs) silenced by CpG
      methylation uncovers the molecular mechanism of tumorigenesis and potential tumor
      biomarkers. Loss of heterozygosity at 11q25 is common in multiple tumors
      including nasopharyngeal carcinoma (NPC). OPCML, located at 11q25, is one of the
      downregulated genes we identified through digital expression subtraction.
      METHODOLOGY/PRINCIPAL FINDINGS: Semi-quantitative RT-PCR showed frequent OPCML
      silencing in NPC and other common tumors, with no homozygous deletion detected by
      multiplex differential DNA-PCR. Instead, promoter methylation of OPCML was
      frequently detected in multiple carcinoma cell lines (nasopharyngeal, esophageal,
      lung, gastric, colon, liver, breast, cervix, prostate), lymphoma cell lines (non
      Hodgkin and Hodgkin lymphoma, nasal NK/T-cell lymphoma) and primary tumors, but
      not in any non-tumor cell line and seldom weakly methylated in normal epithelial
      tissues. Pharmacological and genetic demethylation restored OPCML expression,
      indicating a direct epigenetic silencing. We further found that OPCML is stress
      responsive, but this response is epigenetically impaired when its promoter
      becomes methylated. Ecotopic expression of OPCML led to significant inhibition of
      both anchorage-dependent and -independent growth of carcinoma cells with
      endogenous silencing. CONCLUSIONS/SIGNIFICANCE: Thus, through functional
      epigenetics, we identified OPCML as a broad tumor suppressor, which is frequently
      inactivated by methylation in multiple malignancies.

PMID- 18714357
TI  - A high-temporal resolution technology for dynamic proteomic analysis based on 35S
      labeling.
AB  - As more and more research efforts have been attracted to dynamic or differential
      proteomics, a method with high temporal resolution and high throughput is
      required. In present study, a (35)S in vivo Labeling Analysis for Dynamic
      Proteomics (SiLAD) was designed and tested by analyzing the dynamic proteome
      changes in the highly synchronized A549 cells, as well as in the rat liver 2/3
      partial hepatectomy surgery. The results validated that SiLAD technique, in
      combination with 2-Dimensional Electrophoresis, provided a highly sensitivity
      method to illustrate the non-disturbed endogenous proteins dynamic changes with a
      good temporal resolution and high signal/noise ratio. A significant number of
      differential proteins can be discovered or re-categorized by this technique.
      Another unique feature of SiLAD is its capability of quantifying the rate of
      protein expression, which reflects the cellular physiological turn points more
      effectively. Finally, the prescribed SiLAD proteome snapshot pattern could be
      potentially used as an exclusive symbol for characterizing each stage in well
      regulated biological processes.

PMID- 18714358
TI  - Origin of co-expression patterns in E. coli and S. cerevisiae emerging from
      reverse engineering algorithms.
AB  - BACKGROUND: The concept of reverse engineering a gene network, i.e., of inferring
      a genome-wide graph of putative gene-gene interactions from compendia of high
      throughput microarray data has been extensively used in the last few years to
      deduce/integrate/validate various types of "physical" networks of interactions
      among genes or gene products. RESULTS: This paper gives a comprehensive overview
      of which of these networks emerge significantly when reverse engineering large
      collections of gene expression data for two model organisms, E. coli and S.
      cerevisiae, without any prior information. For the first organism the pattern of
      co-expression is shown to reflect in fine detail both the operonal structure of
      the DNA and the regulatory effects exerted by the gene products when co
      participating in a protein complex. For the second organism we find that direct
      transcriptional control (e.g., transcription factor-binding site interactions)
      has little statistical significance in comparison to the other regulatory
      mechanisms (such as co-sharing a protein complex, co-localization on a metabolic
      pathway or compartment), which are however resolved at a lower level of detail
      than in E. coli. CONCLUSION: The gene co-expression patterns deduced from
      compendia of profiling experiments tend to unveil functional categories that are
      mainly associated to stable bindings rather than transient interactions. The
      inference power of this systematic analysis is substantially reduced when passing
      from E. coli to S. cerevisiae. This extensive analysis provides a way to describe
      the different complexity between the two organisms and discusses the critical
      limitations affecting this type of methodologies.

PMID- 18714359
TI  - Evaluation of two new commercial tests for the diagnosis of acute dengue virus
      infection using NS1 antigen detection in human serum.
AB  - BACKGROUND: We compared the performance of two new commercial tests for the
      detection of dengue NS1 protein during the clinical phase of dengue virus (DENV)
      infection-an immunochromatographic test allowing rapid detection of the NS1
      antigen, Dengue NS1 Ag STRIP (Bio-Rad Laboratories - Marnes La Coquette, France),
      and a two-step sandwich-format microplate enzyme-linked immunosorbent assay
      (ELISA), pan-E Dengue Early ELISA (Panbio - Brisbane, Australia)-with a one-step
      sandwich-format microplate ELISA, the Platelia Dengue NS1 Ag test (Bio-Rad).
      METHODS: We tested 272 serum samples from patients with dengue disease. Of these,
      222 were from patients with acute infection of one of the four dengue serotypes,
      detected by RT-PCR and/or virus isolation. Forty-eight acute-phase serum samples
      from patients not infected with dengue virus were also included. RESULTS: The
      sensitivity of the Platelia Dengue NS1 Ag test on acute serum samples (n = 222)
      was 87.4% (95% confidence interval: 82.3% to 91.5%); that of Dengue NS1 Ag STRIP
      was 81.5% (95% CI: 75.8% to 86.4%) after 15 minutes and 82.4% (95% CI: 76.8% to
      87.2%) after 30 minutes. Both tests had a specificity of 100% (97.5% CI, one
      sided test: 92.6% to 100.0%). The pan-E Dengue Early ELISA had a sensitivity of
      60.4% (95% CI: 53.4% to 66.8%) and a specificity of 97.9% (95% CI: 88.9% to
      99.9%). CONCLUSION: Our findings support the use of diagnostic tools based on the
      NS1 antigen detection for the diagnosis of acute DENV infection. The
      immunochromatographic test, Dengue NS1 Ag STRIP-the first rapid diagnostic test
      for DENV infection-was highly sensitive and specific, and would therefore be a
      suitable first-line test in the field. The pan-E Dengue Early ELISA was less
      sensitive than the Platelia test; this two-step ELISA should be combined with
      DENV IgM antibody detection for the diagnosis of DENV infection.

PMID- 18714360
TI  - The GCR2 gene family is not required for ABA control of seed germination and
      early seedling development in Arabidopsis.
AB  - BACKGROUND: The plant hormone abscisic acid (ABA) regulates diverse processes of
      plant growth and development. It has recently been proposed that GCR2 functions
      as a G-protein-coupled receptor (GPCR) for ABA. However, the structural
      relationships and functionality of GCR2 have been challenged by several
      independent studies. A central question in this controversy is whether gcr2
      mutants are insensitive to ABA, because gcr2 mutants were shown to display
      reduced sensitivity to ABA under one experimental condition (e.g. 22 degrees C,
      continuous white light with 150 micromol m(-2) s(-1)) but were shown to display
      wild-type sensitivity under another slightly different condition (e.g. 23 degrees
      C, 14/10 hr photoperiod with 120 micromol m(-2) s(-1)). It has been hypothesized
      that gcr2 appears only weakly insensitive to ABA because two other GCR2-like
      genes in Arabidopsis, GCL1 and GCL2, compensate for the loss of function of GCR2.
      PRINCIPAL FINDINGS: In order to test this hypothesis, we isolated a putative loss
      of-function allele of GCL2, and then generated all possible combinations of
      mutations in each member of the GCR2 gene family. We found that all double
      mutants, including gcr2 gcl1, gcr2 gcl2, gcl1 gcl2, as well as the gcr2 gcl1 gcl2
      triple mutant displayed wild-type sensitivity to ABA in seed germination and
      early seedling development assays, demonstrating that the GCR2 gene family is not
      required for ABA responses in these processes. CONCLUSION: These results provide
      compelling genetic evidence that GCR2 is unlikely to act as a receptor for ABA in
      the context of either seed germination or early seedling development.

PMID- 18714361
TI  - Entamoeba shows reversible variation in ploidy under different growth conditions
      and between life cycle phases.
AB  - Under axenic growth conditions, trophozoites of Entamoeba histolytica contain
      heterogenous amounts of DNA due to the presence of both multiple nuclei and
      different amounts of DNA in individual nuclei. In order to establish if the DNA
      content and the observed heterogeneity is maintained during different growth
      conditions, we have compared E. histolytica cells growing in xenic and axenic
      cultures. Our results show that the nuclear DNA content of E. histolytica
      trophozoites growing in axenic cultures is at least 10 fold higher than in xenic
      cultures. Re-association of axenic cultures with their bacterial flora led to a
      reduction of DNA content to the original xenic values. Thus switching between
      xenic and axenic growth conditions was accompanied by significant changes in the
      nuclear DNA content of this parasite. Changes in DNA content during encystation
      excystation were studied in the related reptilian parasite E. invadens. During
      excystation of E. invadens cysts, it was observed that the nuclear DNA content
      increased approximately 40 fold following emergence of trophozoites in axenic
      cultures. Based on the observed large changes in nuclear size and DNA content,
      and the minor differences in relative abundance of representative protein coding
      sequences, rDNA and tRNA sequences, it appears that gain or loss of whole genome
      copies may be occurring during changes in the growth conditions. Our studies
      demonstrate the inherent plasticity and dynamic nature of the Entamoeba genome in
      at least two species.

PMID- 18714362
TI  - Co-opted JNK/SAPK signaling in Wnt/beta-catenin-induced tumorigenesis.
AB  - Aberrant stimulation of the canonical Wnt pathway induces mammary tumorigenesis
      in mice. It has been well documented that two types of tumors, adenocarcinoma and
      adenocarcinoma with squamous metaplasia, develop in these mutants. However, the
      molecular mechanism underlying the induction of squamous transdifferentiation
      remains largely unknown. Here, we show that JNK/SAPK signaling plays an important
      role in Wnt-dependent mammary development and malignant transformation. The
      JNK/SAPK pathway is stimulated in pregnancy-mediated lobulo-alveolar
      morphogenesis, a process highly dependent on Wnt/beta-catenin signaling. Strong
      elevations of JNK/SAPK signaling are associated with squamous metaplasia of the
      Wnt-induced adenocarcinoma. Reconstitution of beta-catenin and JNK/SAPK signaling
      activities also promotes expression of the squamous cell marker in cultured
      epithelial cells. Furthermore, a synergistic activation of these two pathways can
      be identified in the malignant squamous cells of human endometrial and lung
      cancers. This is potentially a significant discovery in modern cancer therapy
      because of the effectiveness of an angiogenesis inhibitor, Avastin, for the
      treatment of adenocarcinoma, but not squamous cell carcinoma, in human lung
      cancers. Our finding may improve the usage of biomarkers to distinguish these two
      poorly differentiated tumor types, sharing similar histologic features.

PMID- 18714363
TI  - Cell membrane proteomic analysis identifies proteins differentially expressed in
      osteotropic human breast cancer cells.
AB  - Metastatic breast cancer cells are characterized by their high propensity to
      colonize the skeleton and form bone metastases, causing major morbidity and
      mortality. Identifying key proteins involved in the osteotropic phenotype would
      represent a major step toward the development of both new prognostic markers and
      new effective therapies. Cell surface proteins differentially expressed in cancer
      cells are preferred potential targets for antibody-based targeted therapies. In
      this study, using cell surface biotinylation and a mass spectrometric approach,
      we have compared the profile of accessible cell surface proteins between the
      human breast cancer cell line MDA-MB-231 and its highly osteotropic B02 subclone.
      This strategy allowed the identification of several proteins either up- or
      downregulated in the osteotropic cell line, and differential protein expressions
      were validated using antibody-based techniques. Class I HLAs were down-regulated
      in the bone metastatic variant, whereas alpha(v)beta(3) integrins, among others,
      were consistently up-regulated in this latter cell line. These results show that
      comprehensive profiling of the cell surface proteome of mother cancerous cell
      lines and derived organ-specific metastatic cell lines provides an effective
      approach for the identification of potential accessible marker proteins for both
      prognosis and antibody-based targeted therapies.

PMID- 18714364
TI  - Expression of class I histone deacetylases indicates poor prognosis in
      endometrioid subtypes of ovarian and endometrial carcinomas.
AB  - Histone deacetylase (HDAC) inhibitors are an emerging class of targeted cancer
      therapeutics, and little is known about HDAC expression in gynecologic
      malignancies. Therefore, we tested the hypothesis whether high-level expression
      of class 1 HDACs (HDAC1, 2, and 3) is associated with clinically distinct subsets
      of ovarian and endometrial carcinomas. Expression was assessed by
      immunohistochemistry in a population-based cohort of 465 ovarian and 149
      endometrial carcinomas and correlated with clinicopathologic parameters. Each of
      the HDACs was expressed at high levels in most ovarian (HDAC1, 61%; HDAC2, 93%;
      HDAC3, 84%) and endometrial (HDAC1, 61%; HDAC2, 95%; HDAC3, 83%) carcinomas.
      Further, 55% and 56% of ovarian and endometrial carcinomas, respectively,
      expressed all three HDACs at high levels. Such cases were less common among
      endometrioid subtypes of ovarian and endometrial carcinomas (36% and 52% positive
      cases, respectively) compared with high-grade serous subtypes (64 and 69%,
      respectively, P < .001). High-level expression of all three HDACs is associated
      with a poor prognosis in ovarian endometrioid carcinomas (hazard ratio, 6.7; 95%
      confidence interval, 1.9-23.3). The independent prognostic information and the
      overall high rate of expression for class I HDACs suggest that these targets
      should be explored as predictive factors in ovarian and endometrial carcinomas
      prospectively.

PMID- 18714365
TI  - Amorphous Calcium Phosphate Based Composites: Effect of Surfactants and
      Poly(ethylene oxide) on Filler and Composite Properties.
AB  - The uncontrolled aggregation of amorphous calcium phosphate (ACP) particulate
      fillers and their uneven distribution within polymer matrices can have adverse
      effects on the properties of ACP composites. In this paper we assessed the
      influence of non-ionic and anionic surfactants and poly(ethylene oxide) (PEO)
      introduced during the preparation of ACP on the particle size distribution and
      compositional properties of ACP. In addition, the mechanical strength of
      polymeric composites utilizing such fillers with a photo-activated binary
      methacrylate resin was evaluated. Zirconia-hybridized ACP (Zr-ACP) filler and its
      corresponding composite served as controls for this study. Surfactant- and PEO
      ACPs had an average water content of 16.8 % by mass. Introduction of the anionic
      surfactant reduced the median particle diameter about 45 % (4.1 MUm vs. 7.4 MUm
      for the Zr-ACP control). In the presence of PEO, however, the d(m) increased to
      14.1 MUm. There was no improvement in the biaxial flexure strength (BFS) in any
      of the dry composite specimens prepared with the surfactant- and/or PEO-ACPs
      compared to those formulated with Zr-ACP. The BFS of wet composite specimens
      decreased by 50 % or more after a month-long exposure to saline solutions. Other
      types of surfactants and/or polymers as well as alternative surface modification
      protocols need to be explored for their potential to provide better dispersion of
      ACP into the matrix resin and better mechanical performance ACP composites.

PMID- 18714368
TI  - COMMUNITY READINESS AS A MULTIDIMENSIONAL CONSTRUCT.
AB  - Both the organizational studies literature and the community psychology
      literature discuss the importance of readiness when implementing change. Although
      each area emphasizes different characteristics, several common themes are present
      within the literature. The current study integrates and applies organizational
      and community psychology literature in evaluating community readiness in the
      context of a school-community-university collaborative prevention model. Results
      demonstrate (a) that there is substantial agreement between members of community
      prevention teams on the level of readiness of a community; (b) that readiness is
      a cohesive, but multidimensional, construct related to hypothesized community and
      individual characteristics; and (c) that there is small to moderate agreement
      between members of prevention teams and their "agency directors." These results
      support the notion that clear "theories of change" need to be formulated before
      deciding how to assess community readiness, as assessments will vary due to
      several factors: the type of respondent, the level in which analyses are
      conducted, and the specific community domain (i.e., school, workplace
      collaboration, collaboration experience) investigated.

PMID- 18714369
TI  - Effect of Chemical Structure and Composition of the Resin Phase on Vinyl
      Conversion of Amorphous Calcium Phosphate-filled Composites.
AB  - The objective of this study was to elucidate the effect of chemical structure and
      composition of the polymer matrix on the degree of vinyl conversion (DC) of
      copolymers (unfilled resins) and their amorphous calcium phosphate (ACP)
      composites attained upon photo-polymerization. The DC can also be an indicator of
      the relative potential of these polymeric materials to leach out into the oral
      environment un-reacted monomers that could adversely affect their
      biocompatibility. The following resins were examined: 1) 2,2-bis[p-(2'-hydroxy-3'
      methacryloxypropoxy)phenyl]propane (Bis-GMA)/triethylene glycol dimethacrylate
      (TEGDMA) (1:1 mass ratio; BT resin) combined with hydroxyethyl methacrylate
      (HEMA; BTH resin) and with HEMA and zirconyl dimethacrylate (BTHZ resin), 2)
      urethane dimethacrylate (UDMA)/HEMA resins, and 3) pyromellitic glycerol
      dimethacrylate (PMGDMA)/TEGDMA (PT resin). To make composite specimens, resins
      were mixed with a mass fraction of 40 % zirconia-hybridized ACP. Copolymers and
      their composites were evaluated by near infra-red spectroscopy for DC after 1 d
      and 28 d post-cure at 23  degrees C. Inclusion of HEMA into the BT and UDMA
      resins yielded copolymers and composites with the highest DCs. The significantly
      lower DCs of PT copolymers and their composites are attributed to the rigid
      aromatic core structure, tetra-vinyl functionality and limited methacrylate side
      chain flexibility of the surface-active PMGDMA monomer. There was, however, an
      increase in the 28 d DC for the PT materials as there was for the BTHZ system.
      Surprisingly, the usual decrease observed in DC in going from unfilled polymer to
      composite was reversed for the PT system.

PMID- 18714370
TI  - N-Halamine-Based Antimicrobial Additives for Polymers: Preparation,
      Characterization and Antimicrobial Activity.
AB  - A series of 3-alkyl-5,5-dimethylhydantoin derivatives were prepared by reacting
      5,5-dimethylhydantoin with alkyl bromides with different alkyl chain length (C-2
      to C-22). Upon chlorination, the hydration derivatives were transformed into 1
      chloro-3-alkyl-5,5-dimethylhydantoins (CADMH). The structures of the samples were
      fully characterized with FT-IR, (1)H NMR, UV, and DSC analyses. The antimicrobial
      functions of CADMH were challenged with 10(8-9) CFU/mL of Escherichia coli (gram
      negative bacteria) and Staphylococcus aureus (gram-positive bacteria). All the
      samples provided a total kill of the gram-negative and gram-positive bacteria in
      less than 30 min. CADMH were used as antimicrobial additives for polymeric
      materials. It was found that the presence of as low as 1% of CADMH could provide
      the samples with potent antimicrobial functions. The structure-antimicrobial
      efficacy relationships of the CADMH were further discussed.

PMID- 18714372
TI  - The ergogenic effect of recombinant human erythropoietin on VO2max depends on the
      severity of arterial hypoxemia.
AB  - Treatment with recombinant human erythropoietin (rhEpo) induces a rise in blood
      oxygen-carrying capacity (CaO(2)) that unequivocally enhances maximal oxygen
      uptake (VO(2)max) during exercise in normoxia, but not when exercise is carried
      out in severe acute hypoxia. This implies that there should be a threshold
      altitude at which VO(2)max is less dependent on CaO(2). To ascertain which are
      the mechanisms explaining the interactions between hypoxia, CaO(2) and VO(2)max
      we measured systemic and leg O(2) transport and utilization during incremental
      exercise to exhaustion in normoxia and with different degrees of acute hypoxia in
      eight rhEpo-treated subjects. Following prolonged rhEpo treatment, the gain in
      systemic VO(2)max observed in normoxia (6-7%) persisted during mild hypoxia (8%
      at inspired O(2) fraction (F(I)O(2)) of 0.173) and was even larger during
      moderate hypoxia (14-17% at F(I)O(2) = 0.153-0.134). When hypoxia was further
      augmented to F(I)O(2) = 0.115, there was no rhEpo-induced enhancement of systemic
      VO(2)max or peak leg VO(2). The mechanism highlighted by our data is that besides
      its strong influence on CaO(2), rhEpo was found to enhance leg VO(2)max in
      normoxia through a preferential redistribution of cardiac output toward the
      exercising legs, whereas this advantageous effect disappeared during severe
      hypoxia, leaving augmented CaO(2) alone insufficient for improving peak leg O(2)
      delivery and VO(2). Finally, that VO(2)max was largely dependent on CaO(2) during
      moderate hypoxia but became abruptly CaO(2)-independent by slightly increasing
      the severity of hypoxia could be an indirect evidence of the appearance of
      central fatigue.

PMID- 18714371
TI  - Noncanonical DNA motifs as transactivation targets by wild type and mutant p53.
AB  - Sequence-specific binding by the human p53 master regulator is critical to its
      tumor suppressor activity in response to environmental stresses. p53 binds as a
      tetramer to two decameric half-sites separated by 0-13 nucleotides (nt),
      originally defined by the consensus RRRCWWGYYY (n = 0-13) RRRCWWGYYY. To better
      understand the role of sequence, organization, and level of p53 on
      transactivation at target response elements (REs) by wild type (WT) and mutant
      p53, we deconstructed the functional p53 canonical consensus sequence using
      budding yeast and human cell systems. Contrary to early reports on binding in
      vitro, small increases in distance between decamer half-sites greatly reduces p53
      transactivation, as demonstrated for the natural TIGER RE. This was confirmed
      with human cell extracts using a newly developed, semi-in vitro microsphere
      binding assay. These results contrast with the synergistic increase in
      transactivation from a pair of weak, full-site REs in the MDM2 promoter that are
      separated by an evolutionary conserved 17 bp spacer. Surprisingly, there can be
      substantial transactivation at noncanonical (1/2)-(a single decamer) and (3/4)
      sites, some of which were originally classified as biologically relevant
      canonical consensus sequences including PIDD and Apaf-1. p53 family members p63
      and p73 yielded similar results. Efficient transactivation from noncanonical
      elements requires tetrameric p53, and the presence of the carboxy terminal, non
      specific DNA binding domain enhanced transactivation from noncanonical sequences.
      Our findings demonstrate that RE sequence, organization, and level of p53 can
      strongly impact p53-mediated transactivation, thereby changing the view of what
      constitutes a functional p53 target. Importantly, inclusion of (1/2)- and (3/4)
      site REs greatly expands the p53 master regulatory network.

PMID- 18714373
TI  - Novel meta-analysis-derived type 2 diabetes risk loci do not determine
      prediabetic phenotypes.
AB  - BACKGROUND: Genome-wide association (GWA) studies identified a series of novel
      type 2 diabetes risk loci. Most of them were subsequently demonstrated to affect
      insulin secretion of pancreatic beta-cells. Very recently, a meta-analysis of GWA
      data revealed nine additional risk loci with still undefined roles in the
      pathogenesis of type 2 diabetes. Using our thoroughly phenotyped cohort of
      subjects at an increased risk for type 2 diabetes, we assessed the association of
      the nine latest genetic variants with the predominant prediabetes traits, i.e.,
      obesity, impaired insulin secretion, and insulin resistance.
      METHODOLOGY/PRINCIPAL FINDINGS: One thousand five hundred and seventy-eight
      metabolically characterized non-diabetic German subjects were genotyped for the
      reported candidate single nucleotide polymorphisms (SNPs) JAZF1 rs864745,
      CDC123/CAMK1D rs12779790, TSPAN8/LGR5 rs7961581, THADA rs7578597, ADAMTS9
      rs4607103, NOTCH2 rs10923931, DCD rs1153188, VEGFA rs9472138, and BCL11A
      rs10490072. Insulin sensitivity was derived from fasting glucose and insulin
      concentrations, oral glucose tolerance test (OGTT), and hyperinsulinemic
      euglycemic clamp. Insulin secretion was estimated from OGTT data. After
      appropriate adjustment for confounding variables and Bonferroni correction for
      multiple comparisons (corrected alpha-level: p = 0.0014), none of the SNPs was
      reliably associated with adiposity, insulin sensitivity, or insulin secretion
      (all p > or = 0.0117, dominant inheritance model). The risk alleles of ADAMTS9
      SNP rs4607103 and VEGFA SNP rs9472138 tended to associate with more than one
      measure of insulin sensitivity and insulin secretion, respectively, but did not
      reach formal statistical significance. The study was sufficiently powered (1-beta
      = 0.8) to detect effect sizes of 0.19 < or = d < or = 0.25 (alpha = 0.0014) and
      0.13 < or = d < or = 0.16 (alpha = 0.05). CONCLUSIONS/SIGNIFICANCE: In contrast
      to the first series of GWA-derived type 2 diabetes candidate SNPs, we could not
      detect reliable associations of the novel risk loci with prediabetic phenotypes.
      Possible weak effects of ADAMTS9 SNP rs4607103 and VEGFA SNP rs9472138 on insulin
      sensitivity and insulin secretion, respectively, await further confirmation by
      larger studies.

PMID- 18714374
TI  - A Drosophila Smyd4 homologue is a muscle-specific transcriptional modulator
      involved in development.
AB  - BACKGROUND: SET and MYND domain (Smyd) proteins are involved in the
      transcriptional regulation of cellular proliferation and development in
      vertebrates. However, the in vivo functions and mechanisms by which these
      proteins act are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We have used
      biochemical and genetic approaches to study the role of a Smyd protein in
      Drosophila. We identified eleven Drosophila genes that encode Smyd proteins.
      CG14122 encodes a Smyd4 homologue that we have named dSmyd4. dSmyd4 repressed
      transcription and recruited class I histone deacetylases (HDACs). A region of
      dSmyd4 including the MYND domain interacted directly with approximately 150 amino
      acids at the N-termini of dHDAC1 and dHDAC3. dSmyd4 interacts selectively with
      Ebi, a component of the dHDAC3/SMRTER co-repressor complex. During embryogenesis
      dSmyd4 was expressed throughout the mesoderm, with highest levels in the somatic
      musculature. Muscle-specific RNAi against dSmyd4 resulted in depletion of the
      protein and lead to severe lethality. Eclosion is the final moulting stage of
      Drosophila development when adult flies escape from the pupal case. 80% of dSmyd4
      knockdown flies were not able to eclose, resulting in late pupal lethality.
      However, many aspects of eclosion were still able to occur normally, indicating
      that dSmyd4 is likely to be involved in the development or function of adult
      muscle. CONCLUSIONS/SIGNIFICANCE: Repression of transcription by dSmyd4 and the
      involvement of this protein in development suggests that aspects of Smyd protein
      function are conserved between vertebrates and invertebrates.

PMID- 18714375
TI  - Lifelong reduction of LDL-cholesterol related to a common variant in the LDL
      receptor gene decreases the risk of coronary artery disease--a Mendelian
      Randomisation study.
AB  - BACKGROUND: Rare mutations of the low-density lipoprotein receptor gene (LDLR)
      cause familial hypercholesterolemia, which increases the risk for coronary artery
      disease (CAD). Less is known about the implications of common genetic variation
      in the LDLR gene regarding the variability of cholesterol levels and risk of CAD.
      METHODS: Imputed genotype data at the LDLR locus on 1 644 individuals of a
      population-based sample were explored for association with LDL-C level.
      Replication of association with LDL-C level was sought for the most significant
      single nucleotide polymorphism (SNP) within the LDLR gene in three European
      samples comprising 6 642 adults and 533 children. Association of this SNP with
      CAD was examined in six case-control studies involving more than 15 000
      individuals. FINDINGS: Each copy of the minor T allele of SNP rs2228671 within
      LDLR (frequency 11%) was related to a decrease of LDL-C levels by 0.19 mmol/L
      (95% confidence interval (CI) [0.13-0.24] mmol/L, p = 1.5x10(-10)). This
      association with LDL-C was uniformly found in children, men, and women of all
      samples studied. In parallel, the T allele of rs2228671 was associated with a
      significantly lower risk of CAD (Odds Ratio per copy of the T allele: 0.82, 95%
      CI [0.76-0.89], p = 2.1x10(-7)). Adjustment for LDL-C levels by logistic
      regression or Mendelian Randomisation models abolished the significant
      association between rs2228671 with CAD completely, indicating a functional link
      between the genetic variant at the LDLR gene locus, change in LDL-C and risk of
      CAD. CONCLUSION: A common variant at the LDLR gene locus affects LDL-C levels
      and, thereby, the risk for CAD.

PMID- 18714376
TI  - Rapid reversal of chondroitin sulfate proteoglycan associated staining in
      subcompartments of mouse neostriatum during the emergence of behaviour.
AB  - BACKGROUND: The neostriatum, the mouse homologue of the primate caudate/putamen,
      is the input nucleus for the basal ganglia, receiving both cortical and
      dopaminergic input to each of its sub-compartments, the striosomes and matrix.
      The coordinated activation of corticostriatal pathways is considered vital for
      motor and cognitive abilities, yet the mechanisms which underlie the generation
      of these circuits are unknown. The early and specific targeting of striatal
      subcompartments by both corticostriatal and nigrostriatal terminals suggests
      activity-independent mechanisms, such as axon guidance cues, may play a role in
      this process. Candidates include the chondroitin sulfate proteoglycan (CSPG)
      family of glycoproteins which have roles not only in axon guidance, but also in
      the maturation and stability of neural circuits where they are expressed in
      lattice-like perineuronal nets (PNNs). METHODOLOGY/PRINCIPAL FINDINGS: The
      expression of CSPG-associated structures and PNNs with respect to neostriatal
      subcompartments has been examined qualitatively and quantitatively using double
      labelling for Wisteria floribunda agglutinin (WFA), and the mu-opioid receptor
      (muOR), a marker for striosomes, at six postnatal ages in mice. We find that at
      the earliest ages (postnatal day (P)4 and P10), WFA-positive clusters overlap
      preferentially with the striosome compartment. By P14, these clusters disappear.
      In contrast, PNNs were first seen at P10 and continued to increase in density and
      spread throughout the caudate/putamen with maturation. Remarkably, the PNNs
      overlap almost exclusively with the neostriatal matrix. CONCLUSIONS/SIGNIFICANCE:
      This is the first description of a reversal in the distribution of CSPG
      associated structures, as well as the emergence and maintenance of PNNs in
      specific subcompartments of the neostriatum. These results suggest diverse roles
      for CSPGs in the formation of functional corticostriatal and nigrostriatal
      connectivity within the striosome and matrix compartments of the developing
      caudate/putamen.

PMID- 18714377
TI  - Gene expression disruptions of organism versus organ in Drosophila species
      hybrids.
AB  - Hybrid dysfunctions, such as sterility, may result in part from disruptions in
      the regulation of gene expression. Studies of hybrids within the Drosophila
      simulans clade have reported genes expressed above or below the expression
      observed in their parent species, and such misexpression is associated with male
      sterility in multigenerational backcross hybrids. However, these studies often
      examined whole bodies rather than testes or had limited replication using less
      sensitive but global techniques. Here, we use a new RNA isolation technique to re
      examine hybrid gene expression disruptions in both testes and whole bodies from
      single Drosophila males by real-time quantitative RT-PCR. We find two early
      spermatogenesis transcripts are underexpressed in hybrid whole-bodies but not in
      assays of testes alone, while two late-spermatogenesis transcripts seem to be
      underexpressed in both whole-bodies and testes alone. Although the number of
      transcripts surveyed is limited, these results provide some support for a
      previous hypothesis that the spermatogenesis pathway in these sterile hybrids may
      be disrupted sometime after the expression of the early meiotic arrest genes.

PMID- 18714379
TI  - Evidence of the importance of host habitat use in predicting the dilution effect
      of wild boar for deer exposure to Anaplasma spp.
AB  - Foci of tick-borne pathogens occur at fine spatial scales, and depend upon a
      complex arrangement of factors involving climate, host abundance and landscape
      composition. It has been proposed that the presence of hosts that support tick
      feeding but not pathogen multiplication may dilute the transmission of the
      pathogen. However, models need to consider the spatial component to adequately
      explain how hosts, ticks and pathogens are distributed into the landscape. In
      this study, a novel, lattice-derived, behavior-based, spatially-explicit model
      was developed to test how changes in the assumed perception of different
      landscape elements affect the outcome of the connectivity between patches and
      therefore the dilution effect. The objective of this study was to explain changes
      in the exposure rate (ER) of red deer to Anaplasma spp. under different
      configurations of suitable habitat and landscape fragmentation in the presence of
      variable densities of the potentially diluting host, wild boar. The model showed
      that the increase in habitat fragmentation had a deep impact on Habitat Sharing
      Ratio (HSR), a parameter describing the amount of habitat shared by red deer and
      wild boar, weighted by the probability of the animals to remain together in the
      same patch (according to movement rules), the density of ticks and the density of
      animals at a given vegetation patch, and decreased the dilution effect of wild
      boar on deer Anaplasma ER. The model was validated with data collected on deer,
      wild boar and tick densities, climate, landscape composition, host vegetation
      preferences and deer seropositivity to Anaplasma spp. (as a measure of ER) in 10
      study sites in Spain. However, although conditions were appropriate for a
      dilution effect, empirical results did not show a decrease in deer ER in sites
      with high wild boar densities. The model showed that the HSR was the most
      effective parameter to explain the absence of the dilution effect. These results
      suggest that host habitat usage may weaken the predicted dilution effect for tick
      borne pathogens and emphasize the importance of the perceptual capabilities of
      different hosts in different landscapes and habitat fragmentation conditions for
      predictions of dilution effects.

PMID- 18714378
TI  - Borrelia burgdorferi complement regulator-acquiring surface protein 2 does not
      contribute to complement resistance or host infectivity.
AB  - Borrelia burgdorferi, the pathogen of Lyme disease, cycles in nature through
      Ixodes ticks and mammalian hosts. At least five Complement Regulator-Acquiring
      Surface Proteins (BbCRASPs) are produced by B. burgdorferi, which are thought to
      assist spirochetes in host immune evasion. Recent studies established that
      BbCRASP-2 is preferentially expressed in mammals, and elicits robust antibody
      response in infected hosts, including humans. We show that BbCRASP-2 is
      ubiquitously expressed in diverse murine tissues, but not in ticks, reinforcing a
      role of BbCRASP-2 in conferring B. burgdorferi defense against persistent host
      immune threats, such as complement. BbCRASP-2 immunization, however, fails to
      protect mice from B. burgdorferi infection and does not modify disease, as
      reflected by the development of arthritis. An infectious BbCRASP-2 mutant was
      generated, therefore, to examine the precise role of the gene product in
      spirochete infectivity. Similar to wild type B. burgdorferi, BbCRASP-2 mutants
      remain insensitive to complement-mediated killing in vitro, retain full murine
      infectivity and induce arthritis. Quantitative RT-PCR assessment indicates that
      survivability of BbCRASP-2-deficient B. burgdorferi is not due to altered
      expression of other BbCRASPs. Together, these results suggest that the function
      of a selectively expressed B. burgdorferi gene, BbCRASP-2, is not essential for
      complement resistance or infectivity in the murine host.

PMID- 18714380
TI  - The cellular prion protein PrP(c) is involved in the proliferation of epithelial
      cells and in the distribution of junction-associated proteins.
AB  - BACKGROUND: The physiological function of the ubiquitous cellular prion protein,
      PrP(c), is still under debate. It was essentially studied in nervous system, but
      poorly investigated in epithelial cells. We previously reported that PrP(c) is
      targeted to cell-cell junctions of polarized epithelial cells, where it interacts
      with c-Src. METHODOLOGY/FINDINGS: We show here that, in cultured human
      enterocytes and in intestine in vivo, the mature PrP(c) is differentially
      targeted either to the nucleus in dividing cells or to cell-cell contacts in
      polarized/differentiated cells. By proteomic analysis, we demonstrate that the
      junctional PrP(c) interacts with cytoskeleton-associated proteins, such as gamma-
      and beta-actin, alpha-spectrin, annexin A2, and with the desmosome-associated
      proteins desmoglein, plakoglobin and desmoplakin. In addition, co
      immunoprecipitation experiments revealed complexes associating PrP(c), desmoglein
      and c-Src in raft domains. Through siRNA strategy, we show that PrP(c) is
      necessary to complete the process of epithelial cell proliferation and for the
      sub-cellular distribution of proteins involved in cell architecture and
      junctions. Moreover, analysis of the architecture of the intestinal epithelium of
      PrP(c) knock-out mice revealed a net decrease in the size of desmosomal junctions
      and, without change in the amount of BrdU incorporation, a shortening of the
      length of intestinal villi. CONCLUSIONS/SIGNIFICANCE: From these results, PrP(c)
      could be considered as a new partner involved in the balance between
      proliferation and polarization/differentiation in epithelial cells.

PMID- 18714381
TI  - Does high C-reactive protein concentration increase atherosclerosis? The
      Whitehall II Study.
AB  - BACKGROUND: C-reactive protein (CRP), a marker of systemic inflammation, is
      associated with risk of coronary events and sub-clinical measures of
      atherosclerosis. Evidence in support of this link being causal would include an
      association robust to adjustments for confounders (multivariable standard
      regression analysis) and the association of CRP gene polymorphisms with
      atherosclerosis (Mendelian randomization analysis). METHODOLOGY/PRINCIPAL
      FINDINGS: We genotyped 3 tag single nucleotide polymorphisms (SNPs) [+1444T>C
      (rs1130864); +2303G>A (rs1205) and +4899T>G (rs 3093077)] in the CRP gene and
      assessed CRP and carotid intima-media thickness (CIMT), a structural marker of
      atherosclerosis, in 4941 men and women aged 50-74 (mean 61) years (the Whitehall
      II Study). The 4 major haplotypes from the SNPs were consistently associated with
      CRP level, but not with other risk factors that might confound the association
      between CRP and CIMT. CRP, assessed both at mean age 49 and at mean age 61, was
      associated both with CIMT in age and sex adjusted standard regression analyses
      and with potential confounding factors. However, the association of CRP with CIMT
      attenuated to the null with adjustment for confounding factors in both
      prospective and cross-sectional analyses. When examined using genetic variants as
      the instrument for serum CRP, there was no inferred association between CRP and
      CIMT. CONCLUSIONS/SIGNIFICANCE: Both multivariable standard regression analysis
      and Mendelian randomization analysis suggest that the association of CRP with
      carotid atheroma indexed by CIMT may not be causal.

PMID- 18714382
TI  - Owls may use faeces and prey feathers to signal current reproduction.
AB  - BACKGROUND: Many animals communicate by marking focal elements of their home
      range with different kinds of materials. Visual signaling has been demonstrated
      to play a previously unrecognized role in the intraspecific communication of
      eagle owls (Bubo bubo), in both territorial and parent-offspring contexts. Visual
      signals may play a role in a variety of circumstances in this crepuscular and
      nocturnal species. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that a large
      amount of extremely visible white faeces and prey feathers appear during the
      breeding season on posts and plucking sites in proximity to the nest, potentially
      representing a way for eagle owls to mark their territory. We present descriptive
      and experimental evidence showing that faeces and prey remains could act as
      previously unrecognized visual signals in a nocturnal avian predator. This novel
      signaling behavior could indicate the owls' current reproductive status to
      potential intruders, such as other territorial owls or non-breeding floaters.
      Faeces and prey feather markings may also advertise an owl's reproductive status
      or function in mate-mate communication. CONCLUSIONS/SIGNIFICANCE: We speculate
      that faeces marks and plucking may represent an overlooked but widespread method
      for communicating current reproduction to conspecifics. Such marking behavior may
      be common in birds, and we may now be exploring other questions and mechanisms in
      territoriality.

PMID- 18714383
TI  - A resource for transcriptomic analysis in the mouse brain.
AB  - BACKGROUND: The transcriptome of the cerebral cortex is remarkably homogeneous,
      with variations being stronger between individuals than between areas. It is
      thought that due to the presence of many distinct cell types, differences within
      one cell population will be averaged with the noise from others. Studies of
      sorted cells expressing the same transgene have shown that cell populations can
      be distinguished according to their transcriptional profile. METHODOLOGY: We have
      prepared a low-redundancy set of 16,209 full-length cDNA clones which represents
      the transcriptome of the mouse visual cortex in its coding and non-coding
      aspects. Using an independent tag-based approach, CAGE, we confirmed the cortical
      expression of 72% of the clones. Clones were amplified by PCR and spotted on
      glass slides, and we interrogated the microarrays with RNA from flow-sorted
      fluorescent cells from the cerebral cortex of parvalbumin-egfp transgenic mice.
      CONCLUSIONS: We provide an annotated cDNA clone collection which is particularly
      suitable for transcriptomic analysis in the mouse brain. Spotting it on
      microarrays, we compared the transcriptome of EGFP positive and negative cells in
      a parvalbumin-egfp transgenic background and showed that more than 30% of clones
      are differentially expressed. Our clone collection will be a useful resource for
      the study of the transcriptome of single cell types in the cerebral cortex.

PMID- 18714384
TI  - The association of C-reactive protein and CRP genotype with coronary heart
      disease: findings from five studies with 4,610 cases amongst 18,637 participants.
AB  - BACKGROUND: It is unclear whether C-reactive protein (CRP) is causally related to
      coronary heart disease (CHD). Genetic variants that are known to be associated
      with CRP levels can be used to provide causal inference of the effect of CRP on
      CHD. Our objective was to examine the association between CRP genetic variant
      +1444C>T (rs1130864) and CHD risk in the largest study to date of this
      association. METHODS AND RESULTS: We estimated the association of CRP genetic
      variant +1444C>T (rs1130864) with CRP levels and with CHD in five studies and
      then pooled these analyses (N = 18,637 participants amongst whom there were 4,610
      cases). CRP was associated with potential confounding factors (socioeconomic
      position, physical activity, smoking and body mass) whereas genotype (rs1130864)
      was not associated with these confounders. The pooled odds ratio of CHD per
      doubling of circulating CRP level after adjustment for age and sex was 1.13
      (95%CI: 1.06, 1.21), and after further adjustment for confounding factors it was
      1.07 (95%CI: 1.02, 1.13). Genotype (rs1130864) was associated with circulating
      CRP; the pooled ratio of geometric means of CRP level among individuals with the
      TT genotype compared to those with the CT/CC genotype was 1.21 (95%CI: 1.15,
      1.28) and the pooled ratio of geometric means of CRP level per additional T
      allele was 1.14 (95%CI: 1.11, 1.18), with no strong evidence in either analyses
      of between study heterogeneity (I(2) = 0%, p>0.9 for both analyses). There was no
      association of genotype (rs1130864) with CHD: pooled odds ratio 1.01 (95%CI:
      0.88, 1.16) comparing individuals with TT genotype to those with CT/CC genotype
      and 0.96 (95%CI: 0.90, 1.03) per additional T allele (I(2)<7.5%, p>0.6 for both
      meta-analyses). An instrumental variables analysis (in which the proportion of
      CRP levels explained by rs1130864 was related to CHD) suggested that circulating
      CRP was not associated with CHD: the odds ratio for a doubling of CRP level was
      1.04 (95%CI: 0.61, 1.80). CONCLUSIONS: We found no association of a genetic
      variant, which is known to be related to CRP levels, (rs1130864) and having CHD.
      These findings do not support a causal association between circulating CRP and
      CHD risk, but very large, extended, genetic association studies would be required
      to rule this out.

PMID- 18714385
TI  - Atypical BSE (BASE) transmitted from asymptomatic aging cattle to a primate.
AB  - BACKGROUND: Human variant Creutzfeldt-Jakob Disease (vCJD) results from foodborne
      transmission of prions from slaughtered cattle with classical Bovine Spongiform
      Encephalopathy (cBSE). Atypical forms of BSE, which remain mostly asymptomatic in
      aging cattle, were recently identified at slaughterhouses throughout Europe and
      North America, raising a question about human susceptibility to these new prion
      strains. METHODOLOGY/PRINCIPAL FINDINGS: Brain homogenates from cattle with
      classical BSE and atypical (BASE) infections were inoculated intracerebrally into
      cynomolgus monkeys (Macacca fascicularis), a non-human primate model previously
      demonstrated to be susceptible to the original strain of cBSE. The resulting
      diseases were compared in terms of clinical signs, histology and biochemistry of
      the abnormal prion protein (PrPres). The single monkey infected with BASE had a
      shorter survival, and a different clinical evolution, histopathology, and prion
      protein (PrPres) pattern than was observed for either classical BSE or vCJD
      inoculated animals. Also, the biochemical signature of PrPres in the BASE
      inoculated animal was found to have a higher proteinase K sensitivity of the octa
      repeat region. We found the same biochemical signature in three of four human
      patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same
      country as the infected bovine. CONCLUSION/SIGNIFICANCE: Our results point to a
      possibly higher degree of pathogenicity of BASE than classical BSE in primates
      and also raise a question about a possible link to one uncommon subset of cases
      of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE,
      the occurrence of atypical strains should temper the urge to relax measures
      currently in place to protect public health from accidental contamination by BSE
      contaminated products.

PMID- 18714386
TI  - DNA-free recombinant SV40 capsids protect mice from acute renal failure by
      inducing stress response, survival pathway and apoptotic arrest.
AB  - Viruses induce signaling and host defense during infection. Employing these
      natural trigger mechanisms to combat organ or tissue failure is hampered by
      harmful effects of most viruses. Here we demonstrate that SV40 empty capsids
      (Virus Like Particles-VLPs), with no DNA, induce host Hsp/c70 and Akt-1 survival
      pathways, key players in cellular survival mechanisms. We postulated that this
      signaling might protect against organ damage in vivo. Acute kidney injury (AKI)
      was chosen as target. AKI is critical, prevalent disorder in humans, caused by
      nephrotoxic agents, sepsis or ischemia, via apoptosis/necrosis of renal tubular
      cells, with high morbidity and mortality. Systemic administration of VLPs
      activated Akt-1 and upregulated Hsp/c70 in vivo. Experiments in mercury-induced
      AKI mouse model demonstrated that apoptosis, oxidative stress and toxic renal
      failure were significantly attenuated by pretreatment with capsids prior to the
      mercury insult. Survival rate increased from 12% to >60%, with wide dose
      response. This study demonstrates that SV40 VLPs, devoid of DNA, may potentially
      be used as prophylactic agent for AKI. We anticipate that these finding may be
      projected to a wide range of organ failure, using empty capsids of SV40 as well
      as other viruses.

PMID- 18714387
TI  - Culture shapes how we look at faces.
AB  - BACKGROUND: Face processing, amongst many basic visual skills, is thought to be
      invariant across all humans. From as early as 1965, studies of eye movements have
      consistently revealed a systematic triangular sequence of fixations over the eyes
      and the mouth, suggesting that faces elicit a universal, biologically-determined
      information extraction pattern. METHODOLOGY/PRINCIPAL FINDINGS: Here we monitored
      the eye movements of Western Caucasian and East Asian observers while they
      learned, recognized, and categorized by race Western Caucasian and East Asian
      faces. Western Caucasian observers reproduced a scattered triangular pattern of
      fixations for faces of both races and across tasks. Contrary to intuition, East
      Asian observers focused more on the central region of the face.
      CONCLUSIONS/SIGNIFICANCE: These results demonstrate that face processing can no
      longer be considered as arising from a universal series of perceptual events. The
      strategy employed to extract visual information from faces differs across
      cultures.

PMID- 18714388
TI  - Transcriptome-wide assessment of human brain and lymphocyte senescence.
AB  - BACKGROUND: Identifying biological pathways that vary across the age spectrum can
      provide insight into fundamental mechanisms that impact disease and frailty in
      the elderly. Few methodological approaches offer the means to explore this
      question on as broad a scale as gene expression profiling. Here, we have
      evaluated mRNA expression profiles as a function of age in two populations; one
      consisting of 191 individuals with ages-at-death ranging from 65-100 years and
      with post-mortem brain mRNA measurements of 13,216 genes and a second with 1240
      individuals ages 15-94 and lymphocyte mRNA estimates for 18,519 genes. PRINCIPAL
      FINDINGS: Among negatively correlated transcripts, an enrichment of mitochondrial
      genes was evident in both populations, providing a replication of previous
      studies indicating this as a common signature of aging. Sample differences were
      prominent, the most significant being a decrease in expression of genes involved
      in translation in lymphocytes and an increase in genes involved in transcription
      in brain, suggesting that apart from energy metabolism other basic cell processes
      are affected by age but in a tissue-specific manner. In assessing genomic
      architecture, intron/exon sequence length ratios were larger among negatively
      regulated genes in both samples, suggesting that a decrease in the expression of
      non-compact genes may also be a general effect of aging. Variance in gene
      expression itself has been theorized to change with age due to accumulation of
      somatic mutations and/or increasingly heterogeneous environmental exposures, but
      we found no evidence for such a trend here. SIGNIFICANCE: Results affirm that
      deteriorating mitochondrial gene expression is a common theme in senescence, but
      also highlight novel pathways and features of gene architecture that may be
      important for understanding the molecular consequences of aging.

PMID- 18714389
TI  - Distilling artificial recombinants from large sets of complete mtDNA genomes.
AB  - BACKGROUND: Large-scale genome sequencing poses enormous problems to the
      logistics of laboratory work and data handling. When numerous fragments of
      different genomes are PCR amplified and sequenced in a laboratory, there is a
      high imminent risk of sample confusion. For genetic markers, such as
      mitochondrial DNA (mtDNA), which are free of natural recombination, single
      instances of sample mix-up involving different branches of the mtDNA phylogeny
      would give rise to reticulate patterns and should therefore be detectable.
      METHODOLOGY/PRINCIPAL FINDINGS: We have developed a strategy for comparing new
      complete mtDNA genomes, one by one, to a current skeleton of the worldwide mtDNA
      phylogeny. The mutations distinguishing the reference sequence from a putative
      recombinant sequence can then be allocated to two or more different branches of
      this phylogenetic skeleton. Thus, one would search for two (or three) near
      matches in the total mtDNA database that together best explain the variation seen
      in the recombinants. The evolutionary pathway from the mtDNA tree connecting this
      pair together with the recombinant then generate a grid-like median network, from
      which one can read off the exchanged segments. CONCLUSIONS: We have applied this
      procedure to a large collection of complete human mtDNA sequences, where several
      recombinants could be distilled by our method. All these recombinant sequences
      were subsequently corrected by de novo experiments--fully concordant with the
      predictions from our data-analytical approach.

PMID- 18714390
TI  - Neutralization of botulinum neurotoxin by a human monoclonal antibody specific
      for the catalytic light chain.
AB  - BACKGROUND: Botulinum neurotoxins (BoNT) are a family of category A select
      bioterror agents and the most potent biological toxins known. Cloned antibody
      therapeutics hold considerable promise as BoNT therapeutics, but the therapeutic
      utility of antibodies that bind the BoNT light chain domain (LC), a
      metalloprotease that functions in the cytosol of cholinergic neurons, has not
      been thoroughly explored. METHODS AND FINDINGS: We used an optimized hybridoma
      method to clone a fully human antibody specific for the LC of serotype A BoNT
      (BoNT/A). The 4LCA antibody demonstrated potent in vivo neutralization when
      administered alone and collaborated with an antibody specific for the HC. In
      Neuro-2a neuroblastoma cells, the 4LCA antibody prevented the cleavage of the
      BoNT/A proteolytic target, SNAP-25. Unlike an antibody specific for the HC, the
      4LCA antibody did not block entry of BoNT/A into cultured cells. Instead, it was
      taken up into synaptic vesicles along with BoNT/A. The 4LCA antibody also
      directly inhibited BoNT/A catalytic activity in vitro. CONCLUSIONS: An antibody
      specific for the BoNT/A LC can potently inhibit BoNT/A in vivo and in vitro,
      using mechanisms not previously associated with BoNT-neutralizing antibodies.
      Antibodies specific for BoNT LC may be valuable components of an antibody
      antidote for BoNT exposure.

PMID- 18714391
TI  - Aberrant transforming growth factor beta1 signaling and SMAD4 nuclear
      translocation confer epigenetic repression of ADAM19 in ovarian cancer.
AB  - Transforming growth factor-beta (TGF-beta)/SMAD signaling is a key growth
      regulatory pathway often dysregulated in ovarian cancer and other malignancies.
      Although loss of TGF-beta-mediated growth inhibition has been shown to contribute
      to aberrant cell behavior, the epigenetic consequence(s) of impaired TGF
      beta/SMAD signaling on target genes is not well established. In this study, we
      show that TGF-beta1 causes growth inhibition of normal ovarian surface epithelial
      cells, induction of nuclear translocation SMAD4, and up-regulation of ADAM19 (a
      disintegrin and metalloprotease domain 19), a newly identified TGF-beta1 target
      gene. Conversely, induction and nuclear translocation of SMAD4 were negligible in
      ovarian cancer cells refractory to TGF-beta1 stimulation, and ADAM19 expression
      was greatly reduced. Furthermore, in the TGF-beta1 refractory cells, an inactive
      chromatin environment, marked by repressive histone modifications (trimethyl
      H3K27 and dimethyl-H3K9) and histone deacetylase, was associated with the ADAM19
      promoter region. However, the CpG island found within the promoter and first exon
      of ADAM19 remained generally unmethylated. Although disrupted growth factor
      signaling has been linked to epigenetic gene silencing in cancer, this is the
      first evidence demonstrating that impaired TGF-beta1 signaling can result in the
      formation of a repressive chromatin state and epigenetic suppression of ADAM19.
      Given the emerging role of ADAMs family proteins in growth factor regulation in
      normal cells, we suggest that epigenetic dysregulation of ADAM19 may contribute
      to the neoplastic process in ovarian cancer.

PMID- 18714392
TI  - Cdc7-Dbf4 kinase overexpression in multiple cancers and tumor cell lines is
      correlated with p53 inactivation.
AB  - Cdc7 is a conserved serine/threonine kinase essential for the initiation of DNA
      replication, likely by activating the MCM DNA helicase at the G(1-) to S-phase
      transition. Cdc7 kinase activity requires association with its regulatory subunit
      Dbf4/activator of S-phase kinase. Cdc7-Dbf4 is also downstream of the conserved
      Ataxia telangectasia and RAD3-related kinase that responds to stalled replication
      forks or DNA damage. In this study, we found that Cdc7 protein was very low or
      undetectable in normal tissues and cell lines but had increased expression in
      approximately 50% of the 62 human tumor cell lines we examined. Most cell lines
      with increased Cdc7 protein levels also had increased Dbf4 abundance, and some
      tumor cell lines had extra copies of the DBF4 gene. A high expression of Cdc7
      protein was also detected in primary breast, colon, and lung tumors but not in
      the matched normal tissues. We also found a high correlation between p53 loss and
      increased CDC7 and DBF4 expression in primary breast cancers (P = 3.6 x 10(-9)
      and 1.8 x 10(-10), respectively) and in the cancer cell lines we studied.
      Therefore, increased Cdc7-Dbf4 abundance may be a common occurrence in human
      malignancies.

PMID- 18714393
TI  - Erythropoietin promotes the growth of tumors lacking its receptor and decreases
      survival of tumor-bearing mice by enhancing angiogenesis.
AB  - Erythropoietin (Epo), a known hematopoietic growth factor, has been reported to
      promote tumor growth and angiogenesis in Epo receptor (EpoR)-positive tumors, but
      its effects on EpoR-negative tumors have not been clearly shown. Here, we show
      that Epo accelerates the growth of EpoR-negative tumors by promoting tumor
      angiogenesis. Mice were inoculated with Lewis lung carcinoma cells and treated
      with Epo. Erythropoietin accelerated tumor growth and increased intratumoral
      microvessel density, although it did not accelerate Lewis lung carcinoma cell
      tumor proliferation in vitro. To observe the direct effect of Epo on endothelial
      cells, we examined human dermal microvascular endothelial cells (HMVECs) that
      expressed EpoR. Erythropoietin induced the proliferation of HMVECs and protected
      them from H2O2-induced cell death. Erythropoietin activated the extracellular
      signal-regulated kinase signaling pathway and up-regulated the expression of the
      downstream antiapoptotic protein Bcl-xL in HMVECs. Moreover, in both the absence
      and presence of tumors, in vivo treatment of mice with Epo increased circulating
      endothelial progenitor cells. To investigate the role of Epo in a primary tumor
      model, we inoculated the chemical carcinogen methylcholanthrene (MCA)
      subcutaneously into mice at two doses, a high or a low dose, which induced
      fibrosarcoma, and treated them with Epo. Erythropoietin promoted tumor growth
      after MCA inoculation at both doses and decreased the overall survival of the
      mice inoculated with the high-dose MCA. However, Epo did not increase the
      incidence of fibrosarcoma at either dose. Lewis lung carcinoma cells and MCA
      induced fibrosarcomas did not express EpoR. These results suggest that Epo
      accelerates the growth of tumors that lack EpoR expression by promoting tumor
      angiogenesis.

PMID- 18714394
TI  - Myofibroblasts in pulmonary and brain metastases of alveolar soft-part sarcoma: a
      novel target for treatment?
AB  - Alveolar soft-part sarcoma (ASPS) is a rare neoplasm with chromosomal
      translocation that results in ASPL-TFE3 fusion. It is a slow-growing lesion
      associated with a high incidence of pulmonary and brain metastases indicating
      poor survival. We demonstrated that the ASPS metastases include also stromal
      myofibroblasts. These cells proliferate, express smooth-muscle genes, and
      synthesize extracellular matrix proteins, all of which are characteristics of
      activated myofibroblasts. The tumor cells also exhibited stromal components such
      as transforming growth factor beta (TGFbeta)-dependent, hypoxia-regulated
      cytoglobin (stellate cell activation association protein, cytg/STAP) and prolyl 4
      hydroxylase, a collagen cross-linking enzyme. The pulmonary ASPS myofibroblasts
      synthesize serum response factor (SRF), a repressor of Smad3-mediated TGFbeta
      signaling essential for myofibroblast differentiation and Smad3. The
      phosphorylated active Smad3 was found mostly in the tumor cells. The brain tumor
      cells express cytg/STAP, but in contrast to the lung metastases, they also
      express SRF, Smad3, and phospho-Smad3. Halofuginone, an inhibitor of
      myofibroblasts' activation and Smad3 phosphorylation, inhibited tumor development
      in xenografts derived from renal carcinoma cells harboring a reciprocal ASPL-TFE3
      fusion transcript. This inhibition was associated with the inhibition of
      TGFbeta/SRF signaling, with the inhibition of myofibroblasts' activation, and
      with the complete loss in TFE3 synthesis by the tumor cells. These results
      suggest that the myofibroblasts may serve as a novel target for treatment of ASPS
      metastases.

PMID- 18714395
TI  - Predictive value of PTEN and AR coexpression of sustained responsiveness to
      hormonal therapy in prostate cancer--a pilot study.
AB  - One limitation of current biochemical or histologic analysis of advanced prostate
      cancer (PC; T(3)/T(4) +/- N(x) M(x)) is the ability to identify on first
      diagnostic biopsy patients who will make a durable response to hormone ablation
      therapy. The aim of this study was to assess the predictive value (sustained
      response to hormonal therapy and clinical outcome (relapse-free and overall
      survival)) of phosphatase and tensin homolog (PTEN) and the androgen receptor
      (AR) immunoexpression in the presenting biopsy. Analysis was performed on 47
      samples (10 cases of benign prostatic hyperplasia and 37 hormone-naive PCs).
      Patients selected represented two stages in the natural history of PC: The
      "clinical metastatic androgen-responsive" (androgen-dependent PC, ADPC) and the
      "clinical metastatic androgen-resistant" (androgen-independent PC, AIPC). Reduced
      immunoreactivity (IR) of either or both PTEN/AR in the initial hormone-naive PC
      samples was observed with increased frequency in AIPCs. In the ADPC group, low
      PTEN and/or AR-IR was associated with a shorter median relapse-free survival,
      i.e., at 30 months after surgery, the probability of relapse-free survival for
      high expressors of PTEN and AR was 85.7% (SEM = 9.3) compared with only 16.6%
      (SEM = 15.2) in low expressors. At 36 months, only 28.5% (SEM = 9.3) of ADPC high
      expressors had experienced a biochemical relapse compared with 100% of low
      expressors (hazard ratio, 4.6; 95% confidence interval, 4.7-146.8). Further
      studies analyzing the coexpression of PTEN and AR should be undertaken to
      validate this pilot study and the utility of these biomarkers in routine
      histopathologic workup of patients with PC.

PMID- 18714396
TI  - Farnesol, a fungal quorum-sensing molecule triggers apoptosis in human oral
      squamous carcinoma cells.
AB  - Farnesol is a catabolite within the isoprenoid/cholesterol pathway that has
      exhibited significant antitumor activity. Farnesol was recently identified as a
      quorum-sensing molecule produced by the fungal pathogen Candida albicans. In this
      study, we hypothesize that synthetic and Candida-produced farnesol can induce
      apoptosis in vitro in oral squamous cell carcinoma (OSCC) lines. Cell
      proliferation, apoptosis, mitochondrial degradation, and survivin and caspase
      expressions were examined. In addition, global protein expression profiles were
      analyzed using proteomic analysis. Results demonstrated significant decrease in
      proliferation and increase in apoptosis in cells exposed to farnesol and C.
      albicans culture media. Concurrently, protein expression analysis demonstrated a
      significant decrease in survivin and an increase in cleaved-caspase expression,
      whereas fluorescent microscopy revealed the presence of active caspases with
      mitochondrial degradation in exposed cells. A total of 36 differentially
      expressed proteins were identified by proteomic analysis. Among the 26 up
      regulated proteins were those involved in the inhibition of carcinogenesis,
      proliferation suppression, and aging. Most notable among the 10 down-regulated
      proteins were those involved in the inhibition of apoptosis and proteins
      overexpressed in epithelial carcinomas. This study demonstrates that farnesol
      significantly inhibits the proliferation of OSCCs and promotes apoptosis in vitro
      through both the intrinsic and extrinsic apoptotic signaling pathways. In
      addition, we report for the first time the ability of Candida-produced farnesol
      to induce a similar apoptotic response through the same pathways. The capability
      of farnesol to trigger apoptosis in cancer cells makes it a potential tool for
      studying tumor progression and an attractive candidate as a therapeutic agent.

PMID- 18714397
TI  - Clusterin interacts with Paclitaxel and confer Paclitaxel resistance in ovarian
      cancer.
AB  - Optimal debulking followed by chemotherapy is the standard treatment of managing
      late-stage ovarian cancer, but chemoresistance is still a major problem. In this
      study, we compared expression profiles of primary tumor tissue from five long
      term (>8 years) and five short-term (<2 years) ovarian cancer survivors and
      identified clusterin as one of the genes that were significantly up-regulated in
      short-term survivors. We then evaluated the prognostic significance of clusterin
      and its possible correlation with chemoresistance in ovarian cancer by
      immunohistostaining of clusterin in 62 tumor samples from patients with stage
      III, high-grade serous ovarian cancer. After adjusting for debulking status and
      age, Cox regression analyses showed that high levels of clusterin expression
      correlate with poor survival (hazard ratio, 1.07; 95% confidence interval, 1.002
      1.443; P = .04). We also investigated clusterin in paclitaxel resistance by
      modulating the endogenous clusterin expression in ovarian cancer cells and
      treating the cells with purified clusterin. Results indicate that high-clusterin
      expressing ovarian cancer cells are more resistant to paclitaxel. Moreover,
      exposing ovarian cancer cells to exogenous clusterin increases cells' resistance
      to paclitaxel. Finally, using size exclusion chromatography and fluorescently
      labeled paclitaxel, we demonstrated that clusterin binds to paclitaxel. In
      summary, our findings suggest that high levels of clusterin expression increase
      paclitaxel resistance in ovarian cancer cells by physically binding to
      paclitaxel, which may prevent paclitaxel from interacting with microtubules to
      induce apoptosis. Thus, clusterin is a potential therapeutic target for enhancing
      chemoresponsiveness in patients with a high-level clusterin expression.

PMID- 18714398
TI  - Prognostic relevance of hTERT mRNA expression in ductal adenocarcinoma of the
      pancreas.
AB  - Telomerase is thought to play an essential role in tumorigenesis and progression.
      Its activity is directly correlated with the expression of its catalytic subunit,
      human telomerase reverse transcriptase (hTERT). A correlation of transcript
      expression with a poor prognosis has been detected in different human
      malignancies. However, data on hTERT in pancreatic ductal adenocarcinoma (PDAC)
      are purely descriptive so far. Therefore, we evaluated the impact of hTERT
      expression on patients' prognosis. Human telomerase reverse transcriptase mRNA
      isolates from 56 human microdissected PDAC tissues were analyzed by quantitative
      reverse transcription-polymerase chain reaction and multivariate Cox regression
      hazard test. Elevated hTERT transcript levels were measured in 23 of 56 PDAC
      tissues, 33 patients showed no detectable transcripts. Unexpectedly, a low
      expression of hTERT mRNA levels was associated with a worse prognosis for overall
      survival (relative risk = 5.33; P = .013) when compared to high levels, whereas
      undetectable expression showed an intermediate risk of tumor-related death. These
      data challenge previous findings outlining hTERT's negative impact on overall
      survival. The risk pattern obtained in PDAC suggests a more complex regulation of
      hTERT.

PMID- 18714399
TI  - HLA-A2-restricted cytotoxic T lymphocyte epitopes from human heparanase as novel
      targets for broad-spectrum tumor immunotherapy.
AB  - Peptide vaccination for cancer immunotherapy requires identification of peptide
      epitopes derived from antigenic proteins associated with tumors. Heparanase (Hpa)
      is broadly expressed in various advanced tumors and seems to be an attractive new
      tumor-associated antigen. The present study was designed to predict and identify
      HLA-A2-restricted cytotoxic T lymphocyte (CTL) epitopes in the protein of human
      Hpa. For this purpose, HLA-A2-restricted CTL epitopes were identified using the
      following four-step procedure: 1) a computer-based epitope prediction from the
      amino acid sequence of human Hpa, 2) a peptide-binding assay to determine the
      affinity of the predicted protein with the HLA-A2 molecule, 3) stimulation of the
      primary T-cell response against the predicted peptides in vitro, and 4) testing
      of the induced CTLs toward different kinds of carcinoma cells expressing Hpa
      antigens and/or HLA-A2. The results demonstrated that, of the tested peptides,
      effectors induced by peptides of human Hpa containing residues 525-533
      (PAFSYSFFV, Hpa525), 277-285 (KMLKSFLKA, Hpa277), and 405-413 (WLSLLFKKL, Hpa405)
      could effectively lyse various tumor cell lines that were Hpa-positive and HLA-A2
      matched. We also found that these peptide-specific CTLs could not lyse autologous
      lymphocytes with low Hpa activity. Further study revealed that Hpa525, Hpa277,
      and Hpa405 peptides increased the frequency of IFN-gamma-producing T cells
      compared to a negative peptide. Our results suggest that Hpa525, Hpa277, and
      Hpa405 peptides are new HLA-A2-restricted CTL epitopes capable of inducing Hpa
      specific CTLs in vitro. Because Hpa is expressed in most advanced malignant
      tumors, Hpa525, Hpa277, and Hpa405 peptide-based vaccines may be useful for the
      immunotherapy for patients with advanced tumors.

PMID- 18714400
TI  - Host A(2B) adenosine receptors promote carcinoma growth.
AB  - Recent studies suggest that tumor-infiltrating immune cells can benefit the tumor
      by producing factors that promote angiogenesis and suppress immunity. Because the
      tumor microenvironment is characterized by high adenosine levels, we hypothesized
      that the low-affinity A(2B) adenosine receptor located on host immune cells may
      participate in these effects. In the current study, we tested this hypothesis in
      a Lewis lung carcinoma isograft model using A(2B) receptor knockout (A(2B)KO)
      mice. These mice exhibited significantly attenuated tumor growth and longer
      survival times after inoculation with Lewis lung carcinoma compared to wild type
      (WT) controls. Lewis lung carcinoma tumors in A(2B)KO mice contained
      significantly lower levels of vascular endothelial growth factor (VEGF) compared
      to tumors growing in WT animals. This difference was due to VEGF production by
      host cells, which comprised 30 +/- 2% of total tumor cell population. Stimulation
      of adenosine receptors on WT tumor-infiltrating CD45+ immune cells increased VEGF
      production fivefold, an effect not seen in tumor-associated CD45+ immune cells
      lacking A(2B) receptors. In contrast, we found no significant difference in VEGF
      production between CD45- tumor cells isolated from WT and A(2B)KO mice. Thus, our
      data suggest that tumor cells promote their growth by exploiting A(2B) adenosine
      receptor-dependent regulation of VEGF in host immune cells.

PMID- 18714401
TI  - C-kit and its ligand stem cell factor: potential contribution to prostate cancer
      bone metastasis.
AB  - The tyrosine kinase receptor c-kit and its ligand stem cell factor (SCF) have not
      been explored in prostate cancer (PC) bone metastasis. Herein, we found that
      three human PC cell lines and bone marrow stromal cells express a membrane-bound
      SCF isoform and release a soluble SCF. Bone marrow stromal cells revealed strong
      expression of c-kit, whereas PC cells showed very low levels of the receptor or
      did not express it all. Using an experimental model of PC bone metastasis, we
      found that intraosseous bone tumors formed by otherwise c-kit-negative PC3 cells
      strongly expressed c-kit, as demonstrated using immunohistochemical and Western
      blot analyses. Subcutaneous PC3 tumors were, however, c-kit-negative. Both bone
      and subcutaneous PC3 tumors were positive for SCF. Immunohistochemical analysis
      of human specimens revealed that the expression frequency of c-kit in epithelial
      cells was of 5% in benign prostatic hyperplasia, 14% in primary PC, and 40% in PC
      bone metastases, suggesting an overall trend of increased c-kit expression in
      clinical PC progression. Stem cell factor expression frequency was more than 80%
      in all the cases. Our data suggest that the bone microenvironment up-regulates c
      kit expression on PC cells, favoring their intraosseous expansion.

PMID- 18714402
TI  - P53-dependent suppression of the human calcyclin gene (S100A6): the role of Sp1
      and of NFkappaB.
AB  - Calcyclin (S100A6) is believed to participate in cell cycle control. It was,
      however, unclear if its expression depends on p53, a key regulator of apoptosis
      and cell cycle. We therefore performed transcription regulation assays in HeLa
      cells and found that wild type p53 suppressed the S100A6 promoter up to 12-fold
      in a dose-dependent manner. In contrast, the well-characterized V143A, R175H,
      R249S, and L344A p53 mutants cloned from human cancers suppressed this promoter
      with a 6 to 9-fold lower efficiency. All the sites mediating the p53-dependent
      suppression were contained in the -167 to +134 fragment of the S100A6 promoter.
      Separate overexpression of either Sp1 or of NFkappaB only partially counteracted
      the p53 inhibitory effect on the S100A6 promoter, while simultaneous
      overexpression of both these transactivators resulted in a complete abolishment
      of the p53 inhibitory effect on this promoter. Sp1 and NFkappaB binding to the
      probes resembling their putative binding sites present in the S100A6 promoter was
      decreased in the presence of wild type p53. We propose that the suppression of
      S100A6 is yet another mechanism by which p53 inhibits proliferation. Insufficient
      suppression of this gene by p53 mutants could well be responsible for calcyclin
      overexpression and cell cycle deregulation observed in cancer tissues.

PMID- 18714403
TI  - Abscisic acid does not influence the subcellular distribution of the HYL1 protein
      from Arabidopsis thaliana.
AB  - HYL1 is a nuclear protein involved in the processing of miRNAs but its exact
      function remains unknown. Arabidopsis thaliana hyl1 mutants exhibit
      hypersensitivity to ABA. We decided to answer the question whether ABA affects
      the HYL1 protein localization within the cell and show that it does not. We also
      studied the expression of HYL1 in different tissues and organs. In this paper we
      show for the first time the expression profile of the HYL1 protein using anti
      HYL1 antibodies. The protein is present in seedlings and mature plants in all
      organs studied, with the highest amount in inflorescences. A. thaliana HYL1
      protein has several repetitions of a 28-amino-acid sequence at the C-terminus
      that confer protein instability. Our bioinformatic analysis of HYL1 homologs in
      different Brassica species shows that this repetition is typical only for
      Arabidopsis. This may suggest a relatively late evolutionary acquisition of the C
      terminal domain.

PMID- 18714404
TI  - [The relationships between the liver, biliary ducts, pancreas, and clinical
      nutrition].

PMID- 18714405
TI  - [Nutrition and chronic alcohol abuse].
AB  - Many patients with chronic alcohol abuse present a clinical picture of
      malnourishment either because of reduced usual intake of essential nutrients or
      because alcohol precludes an appropriate digestion and absorption of the
      different essential elements, vitamins, and minerals. A usual example is vitamin
      A deficiency in these patients. Besides, ethanol metabolic pathways themselves
      (through the ADH and the MEOS system) generate toxic intermediate products
      (acetaldehyde, free radicals) interfering with normal metabolism of essential
      elements, mainly lipids, leading to cellular damage through lipid peroxidation
      mechanisms and impairment of the membrane fluidity, fat deposits (hepatocellular
      steatosis), inflammation secondary to oxidative stress and proinflammatory
      cytokines, activation of stellate cells, fibrogenesis, etc. Nutritional supports
      may be effective to improve alcoholic liver disease. A balanced diet, vitamin
      supplements, and pharmacological therapy with antioxidants in order to recover
      depleted glutathione deposits are recommended. It is paramount that these
      patients have a multidisciplinary clinical approach to resolve the problem of
      alcohol dependency.

PMID- 18714406
TI  - [Liver cirrhosis and encephalopathy: clinical and metabolic consequences and
      nutritional support].
AB  - Cirrhosis represents the final stage of many chronic liver diseases and is
      associated to more or less pronounced hyponutrition, independently of the
      etiology, particularly at advanced stages. Its origin is multifactorial, with
      three factors contributing to it: a) limitation or decrease of intake; b)
      impairment in nutrients digestion or absorption; and c) the interference with
      nutrients metabolism. A poor nutritional status is associated with a poor
      survival prognosis. Whether caloric-protein malnourishment (CPM) is an
      independent predictor of mortality or only a marker of the severity of liver
      failure is subject to controversy. There is no consensus on which are the best
      diagnostic criteria for CPM in cirrhosis. Assessment of hyponutrition is
      extremely difficult since both the disease itself and the triggering or etiologic
      factors affect many of the parameters used. Metabolic impairments mimic a
      hypercatabolic state. These patients have decreased carbohydrate utilization and
      storage capacity and increased protein and fat catabolism leading to depletion of
      protein and lipid reserves. These abnormalities together with decreased nutrients
      intake and absorption are the bases for CPM. The most important metabolic
      impairment in patients with advanced liver disease is the change in amino acids
      metabolism. The plasma levels of branched amino acids (BAA) are decreased and of
      aromatic amino acids (AAA) are increased, which has therapeutic implications.
      Among the consequences of the structural impairments taking place in cirrhosis,
      we may highlight hepatic encephalopathy, defined as impaired central nervous
      system functioning that manifests as a series of neuropsychiatric, neuromuscular,
      and behavioral symptoms. These are due to the inability of the diseased liver to
      metabolize neurotoxins that accumulate in the brain affecting neurotransmitters
      and are attributed to the toxic effect of ammonium on the brain tissue.
      Nutritional therapy brings benefits in the different stages of the disease. In
      the short term, it improves nitrogen balance, decreases the hospital stay, and
      improves liver function. In the long term, it decreases the incidence and
      severity of encephalopathy and improves quality of life. Supplementation with
      enteral nutrition may improve protein intake, decrease the frequency of
      hospitalization, and improve the nutritional status, the immune function and the
      disease severity. Protein restriction is not indicated in compensated cirrhosis.
      A diet containing about 30 kcal/kg/d and 1.2 g of protein/kg/d is recommended. In
      acute encephalopathy temporary protein restriction may be needed, which should
      not last longer than 48 h and be minimized since even in patients with liver
      disease better outcomes are obtained without obtaining severe protein
      restriction. Oral supplementation with BAA slows the progression of liver disease
      and improves survival and quality of life. Supplementation should be done with
      fiber or diets with vegetable proteins, which bring high fiber content and less
      AAA, or either with dairy proteins in addition to a high ratio/nitrogen ratio.

PMID- 18714407
TI  - [Hepatotoxicity in the critically ill patient. The liver under an acute severe
      insult].
AB  - The liver plays an essential role in the metabolism of most of the nutrients
      since it is a mainly metabolic organ carrying out a series of physiological and
      metabolic processes related with protein and energy metabolism. The intestinal
      tract is considered a key element in the development of Multiorgan Dysfunction
      (MOD) or failure by loosing its barrier function (impaired permeability) against
      toxins, bio-products and occasionally intraluminal bacteria secondary to hypoxia,
      one of the main pathophysiogenic mechanisms being the insufficient blood flow to
      splacnic organs. Liver dysfunction and/or impairment of liver function test are a
      common event in critically ill patients. They may be due to previous liver
      cirrhosis or to more immediate causes of liver failure such as sepsis, drugs,
      liver transplant or any of the multiple etiologies for hepatitis.

PMID- 18714408
TI  - [Parenteral nutrition-associated liver disease].
AB  - Parenteral nutrition associated liver disease (PNALD) is an important problem in
      patients who require longterm parenteral nutrition as well as in preterm infants.
      Prevalence varies according to different series. Clinical presentation is
      different in adults and infants. Although since its first descriptions several
      hypothesis have been elucidated, the aetiology is not quite clear. It is possible
      that different factors could be involved. PNALD risk factors can be classified in
      three groups: 1) those derived from the lack of enteral nutrition stimulus; 2)
      parenteral nutrition components acting as toxic or the lack of specific nutrients
      and 3) those due to the underlying disease. If PNALD appears in short-term PN and
      it presents only as a mild elevation of liver enzymes, there is no need to treat.
      On the contrary, when direct bilirubin is > 2 mg/dL and lasts longer, there is a
      need to consider different causes and to minimize risk factors. We review the
      different approaches to manage PNALD, including optimizing enteral nutrition,
      modify parenteral solutions, use of specific nutrients -taurine, choline, etc.-
      or the use of drugs (mainly ursodeoxicolic acid). If liver disease progresses to
      cirrhosis a liver transplant must be considered.

PMID- 18714409
TI  - [Liver transplant. Nutritional implications].
AB  - Most of the patients who are candidate to liver transplant have varying degrees
      of hyponutrition. That is why they may be subsidiary to receive nutritional
      therapy so as to improve their nutritional status and the transplant outcomes.
      However, preoperative support is difficult to perform in many cases due to
      multiple factors among which the patients clinical situation, the diagnostic
      requirements, the therapeutic regimens, and extra-hospital care of the "stable"
      candidates may be listed. In the post-surgical phase, the patients must receive
      nutritional support in the same way other patients submitted to major surgery do.
      Early enteral nutrition is the most appropriate method in most of the cases, for
      which intraoperative placement of a transpyloric access to the digestive tract is
      recommended, usually through a naso-jejunal tube. Enteral nutrition should be
      maintained until nutritional requirements may appropriately be covered by oral
      feeding. Immunosuppressive therapy importantly contributes to the development of
      such problems after transplantation through its secondary metabolic-nutritional
      effects. The patients require nutritional follow-up not only to assess the
      evolution of their nutritional status but also to detect, prevent, and treat late
      onset impairments such as obesity, hyperlipidemia, or osteoporosis, which
      commonly occur in these patients.

PMID- 18714410
TI  - [Nutritional management of the patient after surgery of the biliary tract and
      pancreas].
AB  - A big proportion of patients with biliary and pancreatic surgery present
      preoperative malnourishment aggravated by perioperative fasting and additional
      therapies. Surgery of the pancreas and the biliary tract may cause digestive
      impairments, mainly absorptive, especially with fat malabsorption. Many studies
      have shown the usefulness of nutritional support in gastrointestinal surgery. In
      the last years, there has been a remarkable effort in order to determine which
      are the best perioperative nutrition regimens in biliary and pancreatic surgery,
      particularly in the setting of duodenopancreatectomy. Generally, routinary
      parenteral nutrition (PNT) is not recommended, excepting in moderate-severe
      hyponutrition, the first choice therapy being enteral nutrition. Immunonutrition
      seems to improve the outcomes, and the best infusion might be cyclic. According
      to a survey carried out among the Hepatopancreatobiliary Surgery units in Spain,
      nowadays the most frequently used support regimen in biliary and pancreatic
      surgery is PNT, switching to oral feeding within 4-6 days. Enteral nutrition is
      seldom used.

PMID- 18714411
TI  - [Nutritional management of patients with acute pancreatitis: when the past is
      present].
AB  - Patients with acute pancreatitis usually present nutritional status impairment.
      In alcoholic pancreatitis this impairment is usually presented before hospital
      admission. In patients with long-term complicated pancreatitis, malnutrition
      develops during the course of the disease. Besides, these patients present an
      increased stress and protein hypercatabolism. Treatment of acute pancreatitis
      usually maintains patients in a short period of starvation. In mild pancreatitis,
      starvation is needed for a few days, beginning progressively oral feeding. These
      patients don't need special nutritional support, unless they were previously
      malnourished. Patients with severe acute pancreatitis should always receive
      artificial nutritional support in order to preserve the nutritional status as
      starvation will be maintained for more than one week. In this paper, we review
      the nutritional treatment in these situations, trying to answer some different
      questions: type of nutritional support, when it should be started and when it is
      indicated to withdraw.

PMID- 18714413
TI  - [Diabetes and pancreas transplantation].
AB  - Kidney disease is a severe and frequent complication in diabetes. In the terminal
      phase, treatment requires dialysis and, if possible, kidney transplantation.
      Provided that there are no contraindications, simultaneous kidney/pancreas
      transplantation is currently considered the treatment of choice in patients with
      type 1 diabetes mellitus and terminal kidney disease. Pancreas transplantation is
      a complex process initially associated with a greater morbidity than kidney
      transplant alone. At present, however, patient and graft survival is good thereby
      leading to total normalization of metabolic control and allowing the patient to
      carry out a normal life without the need to administer insulin and with the
      consequent benefits in quality of life and the evolution of the complications of
      the disease. The results of pancreas transplant alone are somewhat worse than
      those with combined kidney/pancreas transplantation. They are, however,
      sufficiently satisfactory to be considered a good therapeutic option in patients
      who have previously received a kidney. Nonetheless, the transplantation of the
      pancreas alone in diabetic patients without renal insufficiency or previous
      kidney transplant is another question. Although this type of transplantation
      would be ideal, it currently remains restricted to patients with a labile
      diabetes who require repeated hospital admission due to metabolic decompensation
      and/or severe hypoglycemic episodes accompanied by loss of consciousness.

PMID- 18714412
TI  - [Nutritional repercussions and management of chronic pancreatitis].
AB  - The pancreas is a retroperitoneal organ that releases water, bicarbonate and
      digestive enzymes by the main pancreatic duct (MPD) into the duodenum. Chronic
      pancreatitis (CP) is typically caused, in adults, by chronic alcohol abuse and,
      less frequently hypertriglyceridemia, primary hyperparathyroidism or cystic
      fibrosis. Exocrine dysfunction results in malabsorption of fat and subsequent
      steatorrhea. Damage to pancreatic endocrine function is a late finding in CP and
      results in hyperglycaemia or overt diabetes mellitus. Care of patients with CP
      principally involves management of pain. A significant change in the pain pattern
      or the sudden onset of persistent symptoms suggests the need to rule out other
      potential etiologies, including peptic ulcer disease, biliary obstruction,
      pseudocysts, pancreatic carcinoma, and pancreatic duct stricture or stones, then
      is important to establish a secure diagnosis. Management of pain should then
      proceed in a judicious stepwise approach avoiding opioids dependence. Patients
      should be advised to stop alcohol intake. Fat malabsorption and other
      complications may also arise. Management of steatorrhea should begin with small
      meals and restriction in fat intake. Pancreatic enzyme supplements can relieve
      symptoms and reduce malabsorption in patients who do not respond to dietary
      restriction. Enzymes at high doses should be used with meals. Treatment with acid
      suppression to reduce inactivation of the enzymes from gastric acid are
      recommended. Supplementation with medium chain triglycerides and fat soluble
      vitamin replacement may be required. Management of other complications (such as
      pseudocysts, bile duct or duodenal obstruction, pancreatic ascites, splenic vein
      thrombosis and pseudoaneurysms) often requires aggressive approach with the
      patient kept on total parenteral nutrition to minimize pancreatic stimulation.

PMID- 18714415
TI  - [Collaboration between public health and health assistance in the decrease of
      cardiovascular mortality].

PMID- 18714414
TI  - [Nutrition, cystic fibrosis and the digestive tract].
AB  - The prevalence of hyponutrition in cystic fibrosis is high although it may vary
      according to the different studies. Detection of hyponutrition should be done by
      combining different methods, depending on their availability. However, the
      simplest and most validated criterion is to measure at each visit the weight (and
      height in children) in order to calculate the body mass index and categorizing
      hyponutrition according to absolute criteria: in adults < 18.5 kg/m(2), and in
      children as percentiles of the body mass index. Worsening of the nutritional
      status is directly related with the decrease in lung function parameters and it
      has been proposed as a morbidity (and even mortality) predictive factor in people
      with cystic fibrosis, independently of the level of pulmonary dysfunction.
      Exocrine pancreatic insufficiency is present is approximately 70-90% of the
      patients with cystic fibrosis and the genotype-phenotype correlation is high.
      Most of the patients with exocrine pancreatic insufficiency tolerate a high-fat
      diet provided that they are treated with pancreatic enzymes at appropriate doses.
      The prevalence of diabetes increases with age, reaching up 40% of the cases in
      patients older than 30 years. Clinical liver involvement is less prevalent (it
      approximately affects 1/3 of the patients). Other intestinal complications such
      as meconial ileus, gastroesophageal reflux, obstruction of the distal intestine,
      or fibrosing colon disease may also condition malnourishment. In patients with
      cystic fibrosis, a usual high-fat diet providing 120%-150% of the recommended
      calories is advised. If the nutritional goals are not achieved or maintained with
      diet modifications, artificial supplements may be added, although the
      recommendation for their use has not been endorsed by solid scientific evidences.
      The most frequently used preparations usually are polymeric or hypercaloric. The
      indications for enteral (through a tube, especially gastrostomy) or parenteral
      nutritional support are similar to those used in other pathologies. Dietary and
      nutritional control should be included in a multidisciplinary program allowing
      the improvement of the functional capacity and the quality of life and reducing,
      at least from a theoretical viewpoint, the morbimortality associated to
      malnourishment in these patients.

PMID- 18714416
TI  - [Prevention and control of iodine deficiencies in Spain].

PMID- 18714417
TI  - [Interactive mortality atlas in Andalusia, Spain (AIMA)].
AB  - Until now, mortality atlases have been static. Most of them describe the
      geographical distribution of mortality using count data aggregated over time and
      standardized mortality rates. However, this methodology has several limitations.
      Count data aggregated over time produce a bias in the estimation of death rates.
      Moreover, this practice difficult the study of temporal changes in geographical
      distribution of mortality. On the other hand, using standardized mortality hamper
      to check differences in mortality among groups. The Interactive Mortality Atlas
      in Andalusia (AIMA) is an alternative to conventional static atlases. It is a
      dynamic Geographical Information System that allows visualizing in web-site more
      than 12.000 maps and 338.00 graphics related to the spatio-temporal distribution
      of the main death causes in Andalusia by age and sex groups from 1981. The
      objective of this paper is to describe the methods used for AIMA development, to
      show technical specifications and to present their interactivity. The system is
      available from the link products in www.demap.es. AIMA is the first interactive
      GIS that have been developed in Spain with these characteristics. Spatio-temporal
      Hierarchical Bayesian Models were used for statistical data analysis. The results
      were integrated into web-site using a PHP environment and a dynamic cartography
      in Flash. Thematic maps in AIMA demonstrate that the geographical distribution of
      mortality is dynamic, with differences among year, age and sex groups. The
      information nowadays provided by AIMA and the future updating will contribute to
      reflect on the past, the present and the future of population health in
      Andalusia.

PMID- 18714418
TI  - [Trends in mortality due to cardiovascular diseases in Andalusia, Spain (1975
      2004)].
AB  - BACKGROUND: Cardiovascular diseases are ranked among the leading causes of death
      in the industrialized countries. This study is aimed at ascertaining the
      mortality trends by ischemic heart disease (IHD) and cerebrovascular diseases
      (CVD) in Andalusia within the 1975-2004 period. METHOD: Based on the official IHD
      and CVD death statistics and the related populations, the gross rates (GR) and
      age-adjusted rates (TS) and the Potential Years of Life Lost (PYLL) were
      calculated. To quantify the trends and their change points, a joinpoint
      regression analysis was made. RESULTS: The number of IHD deaths for females rose
      from 2,086 deaths in 1975 to 3,336 in 2004, the TS having dropped from 74.29 to
      50.94 deaths/100,000 females, the PYLL having dropped from 173.65 years to 90.56
      years/100,000 females. The number of deaths for males rose from 2,854 deaths in
      1975 to 4,085 in 2004, the TS having dropped from 147, 67 to 104.96 deaths
      /100,000 males. The PYLL showed a like behaviour from the first to the last year
      of the series, showing values of 716.46 and 460.04 years / 100,000 males. For the
      IHD in females, the number of deaths in absolute numbers dropped from 4,712 to
      4,221, the TS having dropped from 166.00 to 62.08 deaths in females, and the PYLL
      from 338.08 to 87.63 years / 100,000 females. For males, the number of deaths
      dropped from 3,714 to 2,951, the TS from 206.88 deaths /100,000 males in 1975 to
      76.12 /100,000 males in 2004, and the PYLL dropping from 533.12 to 182.38 years /
      100,000 males. CONCLUSIONS: The trend in mortality due to IHD was not constant
      either among females or males, although it has always been a downward trend, the
      drop being statistically significant. The drop in the CVD has been such a major
      one that both the absolute numbers and the gross rates are lower for the most
      recent years that the first years in the series studied despite the aging of
      Andalusias population.

PMID- 18714419
TI  - [Neonatal thyrotropinemia (TSH) as an indicator of iodine nutritional level in
      Castellon and Valencia, Spain (2004-2006)].
AB  - BACKGROUND: In the congenital hypothyroidism screening in populations with
      sufficient iodine intake, in the percentage of newborns with TSH values 5 mU/l
      must be less than 3%. This study is aimed at ascertaining the prevalence of
      iodine deficiency among the mothers and newborns in Castellon and Valencia and,
      secondly, to evaluate the bearing which the day on which the sample is taken and
      the use of iodized antiseptics may have. METHODS: The TSH value was studied in
      91,853 newborns within the 2004-2006 period in Castellon and Valencia. The mean
      TSH values were compared considering the conditions defined by the WHO for
      analyzing the indicator: sampling at two days following birth and no use of
      antiseptics. The percentages of samples having TSH5 > mU/l.were calculated and
      compared. RESULTS: Among the samples having fulfilled the requirements for the
      analysis of the indicator, the prevalence of newborns having TSH5 > mlU/ showed a
      decrease from 2004 (2.2% CI95%:1.8%-2.6%), 2005 (2%; CI95%:1.6%-2.3%) and 2006
      (1.7%; CI95%: 1.4%-2%). The mean TSH in samples of under 2 days was significantly
      higher (2.19 mlU/L; Q1-Q3: 1.35-3.40 as compared to 1.36 mlU/L; Q1-Q3: 0.78-2.21)
      (p<0,001). Considering the samples taken 2 days after birth, the use of
      antiseptics determined a significantly higher mean TSH (1.54 mlU/L; Q1-Q3: 0.88
      2.50 as compared to 1.23 mlU/L; Q1-Q3: 0.72-1.97) (p< 0,001). CONCLUSIONS: The
      value of the newborn thyrotropinemia indicator in Castellon and Valencia is
      compatible with the WHO definition for populations having a proper iodine intake.
      Neonatal TSH screening is a good tool for monitoring the prevalence of iodine
      deficiency, but the point in time of the extraction must be suitable and the use
      of iodized perinatal antiseptics eliminated.

PMID- 18714420
TI  - [1991-2004 follow-up of a Spanish general population cohort. Mortality and
      raising risk factors in the DRECE III Study (Diet and Risk of Cardiovascular
      Diseases in Spain)].
AB  - BACKGROUND: The DRECE III study is based on the follow up of a cohort
      representative of the Spanish general population. The mortality, its main causes
      and relevant risk factors have been analyzed. METHODS: The DRECE cohort is
      composed of 4783 subjects followed since 1991 to 2004 (70930 person-years). In
      1991 a general medical exam including blood analysis and nutritional
      questionnaire was undertaken. Currently the age spam is from 18 to 73 years.
      Vital status and mortality causes were provided by the National Institute of
      Statistics. RESULTS: In this period, 125 deaths were registered: 53 persons
      (42.4%) due to cancer; 31 persons (24.8%) due to circulatory causes, of which 24
      were due to cardiovascular origin. The remaining 41 (32.8%) deaths were included
      under the ICD 10 "Other chapters". For the all causes mortality the independent
      associated variables were: creatinina 1.5 mgr/dl, HR 3.78 (95% CI: 1.52-9.40);
      diabetes, HR 2.80 (95% CI: 1.74-4.46); male sex, HR 2.39 (I95% CI: 1.61-3.55);
      age, HR 1.08 (I95% CI: 1.07-1.10); and gammaglutamil transpeptidasa, HR 1.001
      (I95% CI: 1.000-1.003). In the case of cancer mortality the risk factors founded
      were: age, HR 1.12 (I95% CI: 1.09-1.16); and tobacco, HR 1.33 (I95% CI: 1.14
      1.54). For cardiovascular mortality were creatinina 1.5 mg/dl, HR 19.40 (I95% CI:
      5.45-69.12); diabetes, HR 9.82 (I95% CI: 4.19-23.04); and age, HR 1.10 (I95% CI:
      1.05-1.15). CONCLUSIONS: We obtain a mortality pattern where cancer is the most
      frequent cause. Classic risk factors appear associated to main death causes.
      Diabetes mellitus has an outstanding role as risk factor associated to early
      mortality. No specific diet data was associated neither to all causes mortality,
      nor to cardiovascular or cancer.

PMID- 18714421
TI  - [Degree of knowledge and control in dyslipemia among doctors of Murcia Region,
      Spain (2004-2005)].
AB  - BACKGROUND: Consensus for the treatment and control of lipid abnormalities are
      not always followed, including the calculation of the global cardiovascular risk.
      The aim of this work is to analyse the level of information and patterns of
      action in the detection, assessment and control of dyslipemia among primary care
      and specialising care physicians from the Region of Murcia. METHODS: An
      observational study of transverse type of 14 items was realised among 217 primary
      care doctors (PCD) and 133 specialising care doctors (SCD). RESULTS: The big
      majority (80,9%) of the doctors declared to follow the international consensus
      for the control of the dyslipemia. The cardiovascular risk factor was
      occasionally calculated by 58% of the doctors, whereas the biochemical parameter
      most commonly used was LDL-cholesterol (89,7) followed by the total cholesterol
      (57,7%), HDL-cholesterol (55,7%) and triglycerides (53,1%). The optimal target of
      LDL-cholesterol in primary prevention was <130 mg/dL (66,6% of doctors) whereas
      in secondary prevention was <100 mg/dL (81,7% of doctors). In the case where a
      dyslipidemic patient is regularly controlled, 76,6% of the doctors, maintained
      treatment and 22,3% decreases it. In the case where a dyslipidemic patient is not
      regularly controlled, 62,3% of the doctors would recommend hygienic-dietetic
      treatment and the 66,9% would recommend pharmacological treatment. The best
      valued statin among the doctors was atorvastatin. The 69,1% of the doctors
      usually realise further analytical controls of ALT, AST and CPK to evaluate the
      statin tolerance. The 60,6% of the doctors declared that their patients follow
      their treatment. CONCLUSIONS: In general terms, the knowledge and treatment of
      dyslipemia among primary care and specialising care doctors was proven updated
      and suitable.

PMID- 18714424
TI  - Socioeconomic position and mental health problems in pre- and early-adolescents:
      the TRAILS study.
AB  - BACKGROUND: Family socioeconomic position (SEP) is known to be associated with
      adolescent mental health. Whether the relationship is different for different
      mental health dimensions is unknown. METHODS: Using a cross-sectional design, we
      investigated the differential effects of family SEP on multiple mental health
      dimensions in preadolescents (N = 2230, baseline age 10-12, 49% boys) using
      reports from multiple informants (parent, self, and teachers). A score equal to
      or higher than the 85th percentile (averaged across informants) defined mental
      health problems. RESULTS: SEP was inversely associated with all dimensions.
      Compared to high SEP, the odds ratios (OR) for externalizing problems were 3.88
      (95% confidence interval (CI): 2.56, 5.90) and 2.05 (CI: 1.34, 3.14) for low and
      intermediate SEP, respectively. For internalizing problems, they were 1.86 (CI:
      1.28, 2.70) and 1.37 (CI: 0.94, 2.00), respectively. When adjusted for
      externalizing problems, SEP effects on internalizing problems materially
      attenuated (OR: 1.47, CI: 0.78, 1.68 and OR: 1.34, CI: 0.91, 1.96) while the
      converse was less pronounced (OR: 3.39, CI: 2.24, 5.15) and (OR: 1.91, CI: 1.25,
      2.94). CONCLUSION: In early adolescence, the risk of mental health problems
      increases with decreasing SEP, particularly for externalizing problems. Further,
      the SEP-internalizing problems relationship is partly explained by shared aspects
      with externalizing problems.

PMID- 18714426
TI  - Is it true that I won't be able to drive after I get an implantable cardiac
      defibrillator?

PMID- 18714425
TI  - Growth and antioxidant system of Escherichia coli in response to microcystin-RR.
AB  - Microcystins are a kind of cyclic hepatoxins produced by many species of
      cyanobacteria. The toxic effects of microcystins on animals and plants have been
      well studied. However, the reports about the effects of microcystins on microbial
      cells are very limited. In present paper, Escherichia coli was undertaken to
      determine the effect of microcystin-RR. These results suggested that microcystin
      RR could prolong the growth of E. coli when exposed to high concentrations of
      microcystin-RR and cause the accumulation of ROS and induce the oxidant stress
      for a short time. The antioxidant system protects E. coli from oxidative damage.

PMID- 18714427
TI  - Topical cortisone cream doesn't help heal sunburn.

PMID- 18714428
TI  - Where's the safest position for a child safety seat?

PMID- 18714429
TI  - News of interest: cause of bad breath discovered....

PMID- 18714430
TI  - . . . And honey may prove to be a useful antibiotic.

PMID- 18714431
TI  - Product recalls.  Recalls:  children's blankets...children's hooded jackets with
      drawstrings...and infant rattles.

PMID- 18714432
TI  - Alcoholism and stress: a framework for future treatment strategies. Abstracts of
      a conference. May 6-8, 2008. Volterra, Italy.

PMID- 18714433
TI  - Positioning agriculture and forestry to meet the challenges of climate change.
      Proceedings of a conference. February 6-8, 2007. Baltimore, Maryland, USA.

PMID- 18714434
TI  - Top climate-impacts programme shut.

PMID- 18714435
TI  - The AIDS fight: looking ahead to 2010.

PMID- 18714436
TI  - Complicated peritonitis - the biggest cause of technique failiure.

PMID- 18714437
TI  - The association between low birth weight and type 2 diabetes: contribution of
      genetic factors.
AB  - BACKGROUND: Low birth weight has been associated with an increased risk of type 2
      diabetes in adulthood. Poor fetal nutrition has been suggested to explain this
      association. Our objective was to determine whether genetic factors contribute to
      the association between low birth weight and subsequent risk of type 2 diabetes.
      METHODS: We retrieved information from original birth records on same-sex Swedish
      twins with known zygosity, born from 1926 to 1958. We used regression models to
      investigate whether birth weight was associated with risk of type 2 diabetes in
      the cohort of twins overall, and in case-control analyses within disease
      discordant dizygotic and monozygotic twin pairs. RESULTS: Of 18,230 twins, 592
      (3.2%) had type 2 diabetes. The rate of type 2 diabetes consistently increased
      with decreasing birth weight, from 2.4% among twins with birth weights of 3500 g
      or more to 5.3% among those with birth weights less than 2000 g. In the cohort
      analysis, in which twins are analyzed as independent individuals, the adjusted
      odds ratio (95% confidence interval) of type 2 diabetes per 500-g decrease in
      birth weight was 1.44 (1.28-1.63). When we compared the diseased twin with the
      healthy cotwin, the corresponding odds ratios were 1.38 (1.02-1.85), among
      dizygotic twins, and 1.02 (0.63-1.64), among monozygotic twins. CONCLUSIONS: Low
      birth weight is associated with type 2 diabetes in adulthood. The difference in
      this association between monozygotic and dizygotic twin pairs suggests that
      genetic mechanisms play an important role in this association.

PMID- 18714438
TI  - The role of particle composition on the association between PM2.5 and mortality.
AB  - BACKGROUND: Although the association between exposure to particulate matter (PM)
      mass and mortality is well established, there remains uncertainty about which
      chemical components of PM are most harmful to human health. METHODS: A
      hierarchical approach was used to determine how the association between daily
      PM2.5 mass and mortality was modified by PM2.5 composition in 25 US communities.
      First, the association between daily PM2.5 and mortality was determined for each
      community and season using Poisson regression. Second, we used meta-regression to
      examine how the pooled association was modified by community and season-specific
      particle composition. RESULTS: There was a 0.74% (95% confidence interval = 0.41%
      1.07%) increase in nonaccidental deaths associated with a 10 microg/m3 increase
      in 2-day averaged PM2.5 mass concentration. This association was smaller in the
      west (0.51% [0.10%-0.92%]) than in the east (0.92% [0.23%-1.36%]), and was
      highest in spring (1.88% [0.23%-1.36%]). It was increased when PM2.5 mass
      contained a higher proportion of aluminum (interquartile range = 0.58%), arsenic
      (0.55%), sulfate (0.51%), silicon (0.41%), and nickel (0.37%). The combination of
      aluminum, sulfate, and nickel also modified the effect. These species proportions
      explained residual variability between the community-specific PM2.5 mass effect
      estimates. CONCLUSIONS: This study shows that certain chemical species modify the
      association between PM2.5 and mortality and illustrates that mass alone is not a
      sufficient metric when evaluating health effects of PM exposure.

PMID- 18714439
TI  - Quest for cystic fibrosis pharmacotherapy.

PMID- 18714440
TI  - Meta-analysis: allopurinol in the prevention of postendoscopic retrograde
      cholangiopancreatography pancreatitis.
AB  - BACKGROUND: Several clinical trials evaluating the prophylactic effect of
      allopurinol on postendoscopic retrograde cholangiopancreatography (ERCP)
      pancreatitis have been published; however, there is no consensus on whether
      prophylactic allopurinol can reduce the incidence of post-ERCP pancreatitis. AIM:
      To compare prophylactic allopurinol with placebo on post-ERCP pancreatitis
      reduction by performing a meta-analysis in randomized controlled trials. METHODS:
      Databases including MEDLINE, EMBASE and the Cochrane Library, Science Citation
      Index were searched to find relevant trials. Two reviewers independently
      identified relevant randomized controlled trials assessing the effect of
      prophylactic allopurinol on the incidence of post-ERCP pancreatitis. Outcome
      measures were the incidence of post-ERCP pancreatitis. RESULTS: Four trials
      involving 1730 patients were included. Analysis suggested that post-ERCP
      pancreatitis rates were not significantly different (allopurinol 8.9%, placebo
      9.7%, P = 0.68), RR 0.86 (95% CI: 0.42, 1.77). Subsequent subgroup analysis
      confirmed that allopurinol was not statistically superior to placebo in reducing
      post-ERCP pancreatitis. CONCLUSION: Based on current best evidence, prophylactic
      allopurinol may not be useful for post-ERCP pancreatitis reduction.

PMID- 18714442
TI  - Retraction notice.

PMID- 18714441
TI  - Extent of hepatitis E virus elimination is affected by stabilizers present in
      plasma products and pore size of nanofilters.
AB  - BACKGROUND AND OBJECTIVE: To investigate the physico-chemical properties of
      hepatitis E virus (HEV) with regard to inactivation/removal, we have studied four
      isolates with respect to sensitivity to heat during liquid/dry-heating as well as
      removal by nanofiltration. MATERIALS AND METHODS: Hepatitis E virus in an albumin
      solution or phosphate-buffered saline (PBS) was liquid-heated at 60 degrees C for
      a preset time. HEV in a freeze-dried fibrinogen containing stabilizers was also
      dry-heated at 60 or 80 degrees C for a preset time. In addition, to clarify the
      removal of HEV, the purified virus in PBS was filtered using several types of
      virus-removal filter (nanofilters) that have different pore sizes. HEV
      infectivity or genome equivalents before and after the treatments were assayed by
      a semiquantitative cell-based infectivity assay or quantitative polymerase chain
      reaction assay, respectively. RESULTS: Hepatitis E virus isolates in albumin
      solutions were inactivated slowly at 60 degrees C for 5 h and the resultant log
      reduction factor (LRF) was from 1.0 to > or = 2.2, whereas the virus in PBS was
      inactivated quickly to below the detection limit and the LRF was > or = 2.4 to >
      or = 3.7. The virus in a freeze dried fibrinogen containing trisodium citrate
      dihydrate and l-arginine hydrochloride as stabilizers was inactivated slowly and
      the LRF was 2.0 and 3.0, respectively, of the 72 h at 60 degrees C, but
      inactivated to below the detection limit within 24 h at 80 degrees C with an LRF
      of > or = 4.0. The virus in PBS was also confirmed as to be approximately 35 nm
      in diameter by nanofiltration. These results are useful for evaluating viral
      safety against HEV contamination in blood products. CONCLUSION: The sensitivity
      of HEV to heat was shown to vary greatly depending on the heating conditions. On
      the other hand, the HEV particles were completely removed using 20-nm
      nanofilters. However, each inactivation/removal step should be carefully
      evaluated with respect to the HEV inactivation/removal capacity, which may be
      influenced by processing conditions such as the stabilizers used for blood
      products.

PMID- 18714443
TI  - Concerns on bill's e-script add. Medicare providers cite cost, interoperability
      issues.

PMID- 18714444
TI  - Shopping for a hospital. Ads direct consumers to compare quality measures.

PMID- 18714445
TI  - CBO dampens IT fervor. Execs, lawmaker dispute criticisms.

PMID- 18714446
TI  - FTC lassos Texas victory. Appeals court ruling bolsters antitrust approach.

PMID- 18714447
TI  - The cost of errors. Medicare's new policy could cost the average hospital
      $23,772: study.

PMID- 18714448
TI  - Thomson Reuters' 100 Top Hospitals--2007.

PMID- 18714451
TI  - Finding the pulse. Book says good finances key to hospitals' heartbeat.

PMID- 18714449
TI  - A little off the top. While overall healthcare hiring is up, some health systems
      are being forced to cut jobs, workers and find other savings.
AB  - Despite the oft-repeated theory that the healthcare industry is "recession
      proof," some systems have found themselves resorting to layoffs and budget cuts
      during the current economic downturn. Lee Memorial Health System CFO John Wiest,
      left, said that the system is dealing with reduced operating income and net
      volume, and it has trimmed 415 jobs through attrition.

PMID- 18714450
TI  - Another comparison tool ... with Consumer Reports' online hospital rankings.

PMID- 18714452
TI  - Bumpy beginning for NPI.

PMID- 18714453
TI  - Saving lives, money. New model focuses on 'never events'.

PMID- 18714454
TI  - A shove toward IT. Plan to lure providers to CPOE should be just part of a new
      way to pay for care.

PMID- 18714455
TI  - More kids with chronic disease. N.J. project putting nurse practitioners in
      schools.

PMID- 18714456
TI  - Hard recruitment for smaller markets. Report shows importance of physicians to
      rural hospitals' financial health.

PMID- 18714457
TI  - Treatment options for patients with Bell's palsy.

PMID- 18714458
TI  - Evaluation of Determine HIV-1/2 rapid diagnostic test by 4th generation ELISA
      using blood donors' serum at Felege Hiwot Referral Hospital, northwest Ethiopia.
AB  - OBJECTIVE: The study aims to evaluate the HIV-1/2 rapid diagnostic test kit is
      routinely used to screen HIV infection for safe blood transfusion and VCT
      services in many parts of Ethiopia. METHODS: A total of 324 sera were collected
      from consecutive blood donors from February to May 2006. All samples were
      screened for HIV infection using Determine HIV-1/2 (Abbott Japan) at hospital
      blood bank laboratory. Blindly, all serums were retested at Regional Health
      Research Laboratory using 4th generation ELISA (Vironostika HIV Uni-Form II
      AG/Ab) and Determine HIV-1/2 (Abbott lab). Discordant samples were repeatedly
      retested using the same ELISA and Determine HIV-1/2 to avoid technical errors.
      Finally, discordant results were resolved using Western Blot at the National
      HIV/AIDS Laboratory. RESULTS: Determine HIV-1/2 and ELISA showed 94.4%
      concordance in HIV antibody testing with fair Cohen's Kappa statistic value
      (0.68) among blood donors. The sensitivity, specificity, positive and negative
      predictive values of Determine HIV-1/2 were 60.5%, 98.9%, 88.5% and 94.9%
      respectively. CONCLUSION: As a rapid HIV screening test for blood donors,
      Determine HIV-1/2 showed poor sensitivity. Further evaluation at multiple centres
      is recommended to test its validity as a routine HIV screening test in blood
      donors. Use of a combination of rapid assays is also recommended for screening of
      HIV infection among the donor population.

PMID- 18714459
TI  - [Quantum pharmacology: state of scientific research].
AB  - In the article literature data and own investigations are summarized. Quantum
      pharmacology is defined as science which uses methods of theoretical chemistry
      and quantum mechanics as well as a computer modeling for studying drug molecular
      structure, mechanisms of drug interactions to understand primary pharmacological
      reactions. Main investigations in quantum pharmacology have been carried out in
      these arias: 1. Study of drug molecular structure. 2. Quantitative structure
      activity relationship study (QSAR). 3. Investigations of mechanisms of drugs
      action. 4. Pharmacophores study. 5. De novo drug design. 6. Study of protein
      ligand interactions for description of reactions between drugs and biomolecules
      of organism. 7. Investigations of primary mechanisms of drugs action. Study of
      quantum-pharmacological properties of captopril-inhibitor of
      angiotensineconverting enzyme showed that its molecule belongs to group of soft
      reagents, that's why this substance will interact with soft alkaline substances
      amino acids, unsaturated and aromatic compounds. Quantum-pharmacological
      investigations will favour the discovery of new effective drugs for treatment of
      different diseases.

PMID- 18714460
TI  - [Level of circulating interleukin-16 during preclinical stage of type I diabetes
      mellitus development in children].
AB  - The content of IL16 in blood serum of children with type I diabetes mellitus and
      healthy normoglycemic children with genetic burden of diabetes mellitus and
      positive to autoantibodies against the islets of Langerhans (GADA and IAA) was
      determined by the immunoenzyme method ELISA. Healthy normoglycemic children with
      genetic burden but negative to GADA and IAA and healthy normoglycemic children
      without genetic burden but negative to GADA and IAA have been observed. The
      conducted examinations established that a statistically significant increase in
      the content of IL-16 and its decrease in developed diabetes mellitus patients
      have been noted to have place among children with genetic burden to diabetes,
      positive to GADA and IAA in comparison with control groups.

PMID- 18714461
TI  - [Asthma in childhood. Specific aspects of the PRACTALL consensus report].

PMID- 18714462
TI  - Ethics of medical tourism.

PMID- 18714463
TI  - [Probiotic prophylaxis in patients with predicted severe acute pancreatitis: a
      randomised, double-blind, placebo-controlled trial and informed consent
      procedure].

PMID- 18714464
TI  - [Tick-borne disease or not? Do not let yourself be fooled].

PMID- 18714465
TI  - [Guideline 'Diagnosis and treatment of carpal tunnel syndrome'].

PMID- 18714466
TI  - Primary care. A shot in the arm for community health services.

PMID- 18714467
TI  - Constitution. Signed and delivered--the rules in writing.
AB  - The proposal tucked away in the Darzi report for an NHS constitution could be one
      of the most historic elements of the next stage review, limiting the health
      secretary's power and guaranteeing patient rights.

PMID- 18714468
TI  - Data briefing. Scottish approach is not paying off.

PMID- 18714469
TI  - Public Health. No smoking please, we're British.
AB  - The primary aim of the smoking ban is to reduce secondhand smoking. The public
      has largely supported the ban. Studies indicate smoking prevalence has dropped in
      its first year. Longer-term studies will be available for the three-year review.

PMID- 18714470
TI  - Valuing people. Catch all solution.
AB  - The health of people who have learning disabilities has long been neglected.
      Louise Hunt reports how liaison nurses can improve access to health checks and
      care.

PMID- 18714471
TI  - Coaching. Put a positive spin on things.

PMID- 18714472
TI  - Non-medical workers. Catch the training.

PMID- 18714473
TI  - Education and Imaging. Hepatobiliary and pancreatic: splenic autotransplantation.

PMID- 18714474
TI  - The electronic health record, genetic information, and patient privacy.

PMID- 18714475
TI  - Evaluating participation in insurance plans.

PMID- 18714476
TI  - Utilizing chair cost to evaluate the health plan contracts.

PMID- 18714477
TI  - The patient is always right- or is she?

PMID- 18714478
TI  - Health information technology resources for optometrists.

PMID- 18714479
TI  - [Educational interventions for psychiatric patients under psychotropic
      medication].

PMID- 18714480
TI  - [Nursing care theories].

PMID- 18714481
TI  - IADVL dermatosurgery guidelines: charting uncharted territory.

PMID- 18714482
TI  - [A comment on 'global activity of cancer registries and cancer control and cancer
      incidence statistics in Korea'].

PMID- 18714483
TI  - [Hypertensive retinopathy--assessment].
AB  - The authors intend to make a synthesis of several recent studies available on the
      Internet regarding hypertensive retinopathy. From the physiopathologic point of
      view, it is considered that the blood circulation at the level of the retina,
      choroid and optical nerve has distinct anatomo-physiological properties. It has a
      different response to the changes in the blood pressure, the result consisting of
      distinct individual types of the hypertensive disease which can be rendered
      evident during the optical fundus examination. The retina is considered to be one
      of the target organs in the hypertensive disease. Ascertaining the retinal
      changes has advanced from ophthalmoscopy to digital photography studied with
      appropriate software. The assessment of the hypertensive microangiopathy is
      subjected to a wide intra- and interobserver variability an accurate assessment
      requiring specialized software and standardized protocols. There is also a lack
      of consensus regarding the classification of hypertensive retinopathy and the
      usefulness of retinal examination in the assessment of cardiovascular risk. The
      Keith and Scheie staging scales are still in use, but they do not allow the
      clinician to differentiate slight or even moderate changes at the level of the
      retina of hypertensive patients. Furthermore, they do not correlate enough with
      the severity of the high blood pressure and they are not supported by the
      angiofluorography studies. There are not enough motives for the recommendation of
      a routine ophthalmoscopic examination for all hypertensive patients. It is
      required for patients with stage-3 hypertension. It is also recommended when the
      initial clinical signs are equivocal, as in borderline or fluctuating high blood
      pressure without any other obvious signs from the target organs, for diabetic
      patients, or in the presence of visual symptoms. The clinical implications of
      hypertensive retinopathy being unclear, many of the authors do not recommend
      ophthalmoscopic examination as a rule, or they don't consider the retinal signs
      as being useful for therapeutic decisions.

PMID- 18714484
TI  - [Primary antiphospholipid syndrome].
AB  - Antiphospholipid syndrome (APS) is a disorder characterised by recurrent arterial
      or venous thrombosis and/or pregnancy losses, in the presence of persistently
      elevated levels of anticardiolipin antibodies and/or evidence of circulating
      lupus anticoagulant (these abnormalities are detected by blood tests). Primary
      APS occurs when there is no evidence of associated diseases. APS in the presence
      of an underlying disease, usually systemic lupus erythematosus, is called
      secondary APS.

PMID- 18714485
TI  - [The effects of changes in phosphocalcic metabolism in ocular tissues in patients
      with chronic hemodialysis].
AB  - Extraskeletal calcification is a common complication of chronic renal failure. It
      is well known that in dialysis patients the elevated calcium phosphate product is
      associated with the development of corneal and conjunctival calcification, but
      there is no association between the degree of the calcifications and the levels
      of calcium phosphate product. This paper is supposed to present briefly the main
      hypothesis who explain the mechanism that generates the deposition of the calcium
      salts to the anterior segment of the globe.

PMID- 18714486
TI  - [Macular syndrome].
AB  - The syndrome consists of signs and symptoms associated in a similar clinical
      picture, yet induced by different causes. The macular syndrome represents a
      complex of signs (changes in macular architecture) and symptoms associated with
      central vision disturbances, obviously induced by different causes. Our paper
      reviews the macula alteration causes, the clinical elements of this dysfunction
      and the clinical and paraclinical methods of diagnosis in macular diseases.

PMID- 18714487
TI  - [Normotensive glaucoma].
AB  - Normal tension glaucoma is a form of primary open angle glaucoma where the
      intraocular pressure remains within the normal range. In this case the main
      challenge is to establish the correct diagnosis. The clinical evaluation of a
      patient suspected of a normal tension glaucoma must answer two questions: 1) is
      the intraocular pressure normal and 2) is it a glaucomatous optic neuropathy or
      another type of optic neuropathy?

PMID- 18714488
TI  - Side effect of head and neck radiotherapy: optic neuropathy.
AB  - Therapeutic irradiation of the head and neck region for control of tumor growth
      and for palliation of tumor mass effect, as well as stereotactic surgery
      increased in use in recent years, having a wide applicability. Despite
      technological advances, radiation-induced optic neuropathy is serious
      complication of this kind of treatment. Very important is early recognition of
      the disorder and treatment in incipient phases. Radiation damage could be acute
      (appearing during radiotherapy), early-delayed (occurring within 3 months after
      initial exposure) and late-delayed delayed radionecrosis, within 6 months to 10
      years after exposure). Theories of vascular occlusion, demyelination, free
      radical injury, direct damage to cellular DNA, damage to the blood-brain barrier
      have been proposed to explain the pathophysiology. Patients commonly presents
      with unexplained, painless visual loss in one or both eyes, visual field defects,
      pupillary abnormalities and defective color vision. For both detection and
      management an important tool is Magnetic Resonance Imaging with and without
      contrast agents. Systemic corticosteroids, hyperbaric oxygen therapy free-radical
      scavengers showed some efficiency in treatment, especially in acute phases. A
      promise in treatment shows intravitreal triamcinolone acetonide injections and
      anti-VEGF molecules. But there is still no therapy that has been proven
      effective. The visual prognosis is poor, so we want to raise a alarm signal with
      this paper: awareness of this side-effect and mostly its prevention should be the
      way in managing patients who receive therapeutic irradiation for intracranial,
      sinus, nasopharyngeal, intraorbital and intraocular tumors.

PMID- 18714489
TI  - [Complications of ocular local anesthesia].
AB  - Even as current trends move away from retrobulbar block and topical anesthesia
      gains greater widespread acceptance, ocular anesthesia is most commonly
      administered with a needle. Although rare, complications have been described,
      ranging from innocuous hemorrhage to life-threatening systemic situations.

PMID- 18714490
TI  - [Cataract surgery in pseudoexfoliative syndrome].
AB  - The pseudoexfoliative syndrome is a group of important ocular manifestations of a
      systemic anomaly. Cataract surgery in pseudoexfoliative syndrome implies high
      intra and postoperative risks, because the irido-ciliary and lens changes create
      the background for more frequent complications. Phacoemulsification is the
      preferred method for these patients, and if an adequate and detail-oriented
      surgical technique is used, comparable results can be obtained.

PMID- 18714492
TI  - [Juvenile glaucoma].
AB  - We present the case of a 24 years old patient with advanced juvenile glaucoma.

PMID- 18714491
TI  - [Lyme disease--case report].
AB  - The authors presents a female case of Lyme disease. There are presented types of
      onset, evolution and treatment in this case.

PMID- 18714493
TI  - [Inferior temporal branch arterial occlusion--acute form].
AB  - The authors present the case of a female patient, 72 years old, smoker for 50
      years, with a complex pathology--cardiovascular (coronary artery disease with
      heart failure, hypercoagulable state and 40% left carotid artery stenosis) and
      breast carcinoma--surgically treated, who was admitted in the Ophthalmology
      Clinic of the Emergency Central Military Hospital Bucharest, with the diagnosis
      of Left Eye Branch Retinal Artery Occlusion (temporal inferior) acute form--which
      occurred 10 days ago. The reason of the hospital admission was left eye visual
      field deficit--horizontal (altitudinal), in the superior 1/2 of the visual field,
      but not accompanied by the left eye visual acuity decrease (left eye best
      corrected visual acuity was 20/20--due to the particularity of the case by the
      existence of 2 cilio-retinal arteries at the left eye). Complete ocular and
      systemic work-up was performed. It was decided that at this stage from the
      beginning of the Branch Retinal Artery Occlusion, can be tempted trans-luminal
      photo-embolysis of the embolus located at the origin of the temporal inferior
      branch of the Central Retinal Artery with the Nd: YAG laser--technique which was
      used as national premiere in Romania.

PMID- 18714494
TI  - [Conjunctival nevus--clinical case].
AB  - The authors present the case of a four-year-old patient who came to our clinic
      because of a tumor formation localized at the sclero-corneal level. The
      ophthalmologic examination resulted in the diagnosis of conjunctival malignant
      melanoma and the decision for excision was made. The postoperative anatomo
      pathologic examination disproved the malignant character of the lesion and
      established the diagnosis of conjunctival nevus.

PMID- 18714495
TI  - [Papillary edema in expansive intra-cranial tumors].
AB  - The aim was: correlation between frequency of papillary edema in intra-cranial
      tumours and to verify Romanian medical legislation for ophthalmoscopy. This paper
      is a retrospective study for a period of 2 years (2005-2006). We included in
      study 446 patients treated in Hospital "Sf Treime" Iasi, Romania for expansive
      intra-cranial tumours. Ocular signs and symptoms (especially papillary edema)
      were observed for these patients. Mean age was 50.76+/- 18.30 years and in 46.87%
      of cases we found papillary edema in different stages. CONCLUSIONS: papillary
      edema depends after localization and size of intra-cranial tumours, histological
      aspects and its aggressivity.

PMID- 18714496
TI  - The influence of viscoelastic substances on the corneal endothelium during
      cataract surgery by phacoemulsification.
AB  - PURPOSE: To compare the ability of different ophthalmic viscoelastic devices to
      protect the corneal endothelium following in-the-bag phacoemulsification with
      posterior chamber intraocular lens (IOL) implantation. MATERIAL & METHODS: We
      studied 50 patients with soft to moderately dense (Grade 1-3) cataract and
      corneal endothelial cell density of >2000 cells/mm2. The corneal response to
      surgery was evaluated by measuring the endothelial cell loss, the variation in
      the mean cell area of the endothelial cells (CV), and the central corneal
      thickness, all that by using a TOPCON SP 2000P noncontact, specular microscope.
      Data were recorded preoperatively and postoperatively. RESULTS: Preoperatively no
      statistical significant difference was observed in cell count, CV or pachymetry
      among groups. Postoperatively, all the groups had a statistically significant
      decrease (p < 0.001) in endothelial cell count. There was an equal and
      significant (p < 0.001) increase in visual acuity. Between groups there was no
      statistically significant difference (p > 0.17) in any of the parameters we
      studied. CONCLUSIONS: Between the OVDs we used, either DisCoVisc or ProVisc &
      VisCoat, there was no statistical significant difference neither in surgical
      outcome nor in endothelial layer aspect and function. DisCoVisc protected better
      the endothelium cells even if it was not statistically significant, and is the
      one that can be used for the entire surgical procedure.

PMID- 18714497
TI  - [Laser photocoagulation in retinopathy of prematurity--preliminary results].
AB  - PURPOSE: The present study aims to reveal, on one hand, the efficiency of the
      laser photocoagulation in the Retinopathy of Prematurity (ROP) and, on the other
      one, to answer two questions: 1. Why do some ROPs still go wrong, in spite of
      laser therapy? 2. What can we do about it? MATERIAL/METHOD: A retrospective study
      has been performed, including the 21 prematurely newborns that have been treated
      by laser photocoagulation, for ROP, in Cluj-Napoca, between April 2006-September
      2007. The photocoagulation has been carried out with a diode laser fixed on an
      indirect ophthalmoscope, under sedation, in the Neonatology Department of the
      County Clinical Hospital from Cluj. RESULTS: Globally, the results of the laser
      treatment are the following: favourable outcome (regression of ROP)--in 32 eyes
      (84.21%) and unfavourable outcome--in 6 eyes (15.79%). Laser photocoagulation has
      been performed in 29 eyes in stage III zone 2 and produced the regression of ROP
      in 27 of them (93. 10%). ROP zone I has been identified and treated in 3 cases,
      of which-two had a favourable evolution (66.66%), and one has progressed to stage
      IV (33.33%). ROP in stage IVa has been identified in 3 cases (5 eyes). The laser
      photocoagulation has been possible only in 3 eyes, with favourable evolution in
      one eye (33.33%) and unfavourable, in 2 eyes (66.66%). DISCUSSION: The results of
      the treatment are analyzed according to two parameters: the objective situation
      prior to laser photocoagulation (stage and zone of ROP) and the moment of the
      treatment (postconceptional and postnatal age). CONCLUSIONS: 1. The laser
      photocoagulation has been performed at the right moment, in 17 of the 21 treated
      cases (80.95%). 2. The indirect laser photocoagulation produced the regression of
      ROP in 15 of the 17 cases that were treated at the right moment (88.22%). 3. The
      indirect laser photocoagulation has been possible in 4 of the 7 eyes that arrived
      too late for the treatment and produced the regression of ROP in 3 of them
      (42.85%). 4. If it is not sustained by a correct screening, performed at the
      right moment, the laser photocoagulation cannot maximally validate its healing
      potential in ROP

PMID- 18714498
TI  - [Comparative study of endothelial changes in cataract surgery with
      phacoemulsification technique].
AB  - PURPOSE: The comparative analysis of the corneal endothelium modifications
      (density, pleiomorphism and poly-megetism) appeared as a result of the
      phacoemulsification through divide and conquer (D-C) respectively phaco-chop (P
      C) technique. MATERIAL AND METHOD: One year prospective, observational and
      interventional clinical study on 60 eyes with cataract surgery through
      phacoemulsification by the same surgeon. They were split in 2 groups of study
      according to the hardness of the cataract (Group A-30 eyes with the hardness of
      the cataract 3+ and Group B-30 eyes with the hardness of the cataract 4+). In
      both groups half of the patients were treated with P-C technique surgery and the
      other half with D-C technique surgery. The groups were homogeneous in relation to
      age, cataract density, and without associated systemic and ocular pathology.
      RESULTS: In all cases the endothelial analysis was performed using the
      endothelial direct microscope and the ultrasonic pachymetry in presurgery, in the
      second postoperative day, at 14 days and 2 months. At the end of the study in
      Group A (3+) there were not noticed any significant modifications in loss of the
      endothelial cells through both technique surgery. In Group B (4 =) appeared
      significant modifications with much more losses in (D-C) technique surgeries.
      Ultrasonic pachymetry in the second day of postsurgery has shown temporary
      increase of corneal thickness compared to presurgery due to corneal edema, with
      recovery two months post surgery. CONCLUSIONS: Regardless of the technique,
      phacoemulsification leads to endothelial modifications. In our study the P-C
      technique maintained a better endothelial structure homeostasis.

PMID- 18714499
TI  - [Is dry eye syndrome a professional disease for aeronautical personnel?].
AB  - The purpose of this study is to analyze the eye comfort of the aeronautical
      personnel. This study has been conducted in ophthalmologic office of the National
      Institute of Aeronautical and Space Medicine, for 68 patients (group 1), men and
      women, active aeronautical personnel, between 35-55 years old, apparently
      ophthalmologically normal subjects. First the patients filled out a questionnaire
      that was intended to provide the subjective evaluation; objective investigation
      included: biomicroscopy, fluorescein stain, tear break up time (BUT) and Schirmer
      tear test. There have been found subclinical, mild and moderate dry eye; tear
      substitutes have been prescribed. The patients were re-examined every 3 months,
      for a period of 9 months. Results were compared with those obtained from a
      control group--20 people (group 2), women and men, with ages in the same range,
      people not involved in the aviation field who requested ophthalmological
      examination for optical correction. The results raise the question: can the "Dry
      eye syndrome" be considered a work-related disease? The answer will be "probably
      no" indulging oneself conditions required by International Aeronautical Authority
      (ex. periodically hydration and enough in volume), even if the environmental
      conditions inside the aircraft can produce this disorder. During flight,
      aeronautical personnel should use tear substitutes, because of the low humidity
      of the air inside the aircraft.

PMID- 18714500
TI  - [Assessment of systane in severe dry eye].
AB  - The study proposes the evaluation of the Systane effect on people that have
      severe dry eye sensation, with cornea or conjunctive complications. In order to
      do this, a study protocol has been adopted which meant comparing the values of
      lacrimal film break-up time, before and after Systane treatment, comparing cornea
      and conjunctive staining, comparing the crystallization test before and after
      treatment, comparing the conjunctival impression before and after treatment, and
      the general acceptability of Systane. The study results have shown that in severe
      dry eye cases, Systane increases lacrimal film break-up time by 2-3 seconds than
      the initial value, as well as considerable reduction in cornea/conjunctival
      staining and in conjunctival hyperemia in Sicca keratoconjunctivitis. After
      treatment, conjunctival impression have shown the proliferation of conjunctival
      and goblet cells, with normal morphologic aspect of the new-formed cells. In
      every case, the regenerating effect on epithelia of Systane was obvious, which is
      determined by the direct action of the HP-guar, forming a protective layer with
      lubrication effect, helpful to the initiation of tissue repairing processes.

PMID- 18714501
TI  - [Correlation between structural and functional analysis in glaucoma suspects].
AB  - PURPOSE: To establish correlations between structural and functional parameters
      in glaucoma suspects. METHOD: In 43 patients (83 eyes) of glaucoma patients we
      have performed standard automated perimetry, scanning laser polarimetry (GDx-VCC)
      of the retinal nerve fiber layer (RNFL) and optical coherence tomography (Stratus
      OCT) of the RNFL and optic disc. RESULTS: Diagnostic concordance (achieved if one
      eye is deemed normal--respectively abnormal--by both tests) was 60.24% between
      perimetry and OCT respectively 61.44% between perimetry and GDx. The Areas under
      the Receiver Operating Characteristic curve were between 0.524-0.574 for OCT
      parameters and 0.518-0.548 for GDx parameters (considering the visual field
      examination as "gold standard"). The correlation between RNFL measurements in OCT
      and GDx took values between r = 0.481 and r = 0.352. CONCLUSIONS: Structural and
      functional damage are not consistent with each other in early glaucoma, resulting
      in the fact that both tests should be used in the diagnostic strategy

PMID- 18714502
TI  - [Daily and nightly fluctuation of intraocular pressure and blood pressure in
      glaucoma and non-glaucoma patients].
AB  - PURPOSE: To determine and compare 24-hour fluctuations of intraocular pressure
      (IOP) and systemic blood pressure (BP) in patients with ocular hypertension (OHT)
      and primary open angle glaucoma (POAG) versus non-glaucoma patients. METHODS:
      Applanation IOP and BP were measured every 2 hours by one observer for 24 hours
      in 102 patients. The patients were classified: group 1 - 21 patients with OHT and
      POAG without treatment, group 2 - 40 patients with OHT and POAG with a
      satisfactory diurnal therapeutic control of IOP (daytime IOP ? 21 mmHg), group 3 
      13 patients with POAG with unsatisfactory control of IOP under maximal tolerated
      medication (daytime IOP > 21 mmHg), and group 0-28 non-glaucoma patients (control
      group). RESULTS: In all glaucoma patients groups 24-hour IOP fluctuations were
      greater than in the control group (group 0 - 3.62 +/- 0.82 mmHg, ANOVA p <
      0.001). Untreated OHT/POAG had 24-hour IOP fluctuations significantly greater
      than those with good therapeutic control (group 1 - 5.66 +/- 1.66 mmHg versus
      group 2 - 4.27 +/- 1.86 mmHg, p = 0.0001). POAG with uncontrolled IOP under
      maximal tolerated medication had the 24-hour IOP fluctuations significantly
      greater than the other groups (group 3 - 8.38 +/- 3.78 mmHg, p?0.0001). In these
      patients there was an evident nocturnal mean IOP peak between 0-2 am which
      temporally correlates with nocturnal systemic BP "dip". Nocturnal IOP peaks
      (between 11 pm-7 am) were found more frequently in treated glaucoma patients
      (45.28% - groups 2 and 3 versus 10.2% - groups 0 and 1, p < 0.0001). CONCLUSIONS:
      Circadian lOP fluctuations in glaucoma patients, even with a satisfactory diurnal
      therapeutic control, are greater than in the age-matched control subjects.
      Patients with uncontrolled lOP under topical maximal tolerated medication had the
      greatest 24-hour lOP fluctuations. Nocturnal lOP peaks occur more often in
      medically treated patients and 24-hour monitoring of lOP may be useful in this
      patients.

PMID- 18714503
TI  - [Therapeutic options in thyroid ophthalmopathy].
AB  - One of the most important features in Graves disease is thyroid myopathy. This
      condition accompanies the thyroid dysfunction, that can lead to hyper-, hypo- or
      euthyroidism. The thyroid myopathy is the most common cause of acquired double
      vision in adults. This paper analyzes the evolution of thyroid myopathy, after
      conservative and surgical treatment. MATERIAL AND METHODS: The clinical evolution
      in 15 patients with thyroid myopathy was analyzed. They have been treated
      conservatively with systemic corticosteroids. The orbital, local antiinflammatory
      treatment consisted in Rx antiinflammatory therapy and retrobulbar injections
      with corticosteroids. Three of the patients with restrictive strabismus and
      diplopia were operated on. In 2 of them, with malignant exophthalmia (proptosis),
      orbita decompression was necessary. The surgical strategy and timing in the
      restrictive strabismus is analyzed. In the follow up period, the extent of the
      proptosis (exophthalmometry), the extraocular muscle size (orbital ultrasound)
      and the diplopia (Hess-Lancaster test) were monitored. The clinical evolution in
      one patient treated conservatively and operated on is presented in detail.
      DISCUSSIONS, CONCLUSIONS: The conservative treatment of the thyroid myopathy is
      efficient only in the acute phase. The surgical treatment should be applied when
      muscular fibrosis and restrictive strabismus are present. The timing of surgery
      is indicated after 6 months of stable ocular deviation. Adjustable surgery is the
      most suitable procedure for the restrictive strabismus in thyroid myopathy.

PMID- 18714504
TI  - Lets build a network of engaged, informed physicians to achieve our goals.

PMID- 18714505
TI  - Immunizations by pharmacists--the current state of Iowa regulation.

PMID- 18714506
TI  - Legislative session makes its mark on the state of Iowa.

PMID- 18714507
TI  - IMS releases task force report on Iowa's health care infrastructure.

PMID- 18714508
TI  - Match Day is an important day for Iowa as well as for students.

PMID- 18714509
TI  - QRISK2 vs Framingham.

PMID- 18714510
TI  - No easy way to identify aspirin resistance.

PMID- 18714511
TI  - Managing patients with type 2 diabetes.

PMID- 18714512
TI  - Identify the underlying cause of raised prolactin.

PMID- 18714513
TI  - Allergic reactions. Part 1.

PMID- 18714514
TI  - Change of air. 1908.

PMID- 18714516
TI  - [Abdominal pain and transit disorders following a laparoscopic procedure: be
      alert to a trocar hernia].
AB  - Three patients, three women aged 40, 64 and 75, suffered from a trocar hernia, a
      specific complication of laparoscopic surgery. This type of hernia may result in
      small bowel obstruction and normally appears within two weeks after laparoscopy.
      The usual presentation is that of abdominal pain with nausea and vomiting. Trocar
      herniation implicates the necessity of reposition and might result in bowel
      resection with prolonged hospital stay. The advice for prevention is to use a
      trocar with a diameter as small as possible, as the chance of a hernia occurring
      increases withthe use of larger trocars. Fascial closure is advised for trocars
      to mm and larger. With a growing number of procedures being performed
      laparoscopically, the importance of recognizing and preventing this complication
      is evident. Three cases illustrate the importance of early recognition of small
      bowel obstruction resulting from trocar herniation.

PMID- 18714517
TI  - [Neonatal screening for metabolic diseases: need for efficacy studies].
AB  - Neonatal screening in the Netherlands was extended in 2007. Twelve of the 17
      diseases screened for are metabolic disorders. Only 2 of the metabolic diseases
      part of the neonatal screening programme in the Dutch population had been studied
      prior to the introduction of neonatal screening, namely galactosaemia and medium
      chain acyl-CoA dehydrogenase (MCAD) deficiency. Short-chain acyl-CoA
      dehydrogenase (SCAD) deficiency, a metabolic disease not added to the screening,
      was extensively studied recently. The authors concluded that SCAD deficiency did
      not meet screening criteria. The efficacy of screening should be investigated, as
      the screening test and genetic differences in populations make screening unique
      for each population. Clinical and biochemical phenotype do not always correlate
      with genotype. Differences in the disease population and the screening population
      can make decisions with respect to treatment difficult, especially when many more
      patients are found than expected. Some of these patients might never have become
      ill and should thus not be treated. Further studies are needed to differentiate
      between these patients.

PMID- 18714518
TI  - [Surgical reconstruction of large defects of the nose].
AB  - --Skin cancer of the face is the most prevalent type of cancer. The large
      increase of the incidence of this type of cancer in recent years has resulted in
      an increase of skin cancer resections in the face. --Nasal defects are the most
      challenging of these facial defects. Nasal reconstruction requires reconstruction
      of three tissue layers: the inner mucosal lining, supporting structures
      (cartilage or bone) and the outer cutaneous lining. --The new inner lining should
      consist of well-vascularized thin tissue to prevent rejection of cartilage or
      bone in the supporting layer. For example, septal mucosa or skin can be used in
      various ways to reconstruct the inner lining. --The new supporting structures,
      consisting of transplanted cartilage or bone, should be strong enough to prevent
      contraction of the soft tissues--inner and outer lining--during wound healing. -
      The outer lining is reconstructed per subunit of the nose, e.g. nostril, ala nasi
      or ridge of the nose. Usually a paramedian forehead flap is used for the
      reconstruction of the outer lining.

PMID- 18714519
TI  - [The guideline 'Recurrent miscarriage' (first revision) of the Dutch Society for
      Obstetrics and Gynaecology].
AB  - --In 2007, the Dutch Society for Obstetrics and Gynaecology issued a revised
      version of the 1999 guideline on recurrent miscarriage. --The new guideline was
      developed according to the principles of evidence-based guideline development and
      includes levels of evidence. --The guideline contains recommendations for
      effective diagnosis and treatment and explicitly mentions certain diagnostic
      tests and treatments that should be avoided. --After a thorough investigation of
      a couples'-history, the type of diagnostic tests that should be offered to the
      couple can be determined. Patients with a low risk of having cytogenetic
      abnormalities or thrombophilia may be excluded from parental karyotyping and
      thrombophilia screening, respectively. --Women with confirmed antiphospholipid
      antibody syndrome should be offered anticoagulation treatment before and during
      subsequent pregnancies. --Effective therapy for unexplained recurrent miscarriage
      is lacking. However, the probability of a successful future pregnancy is high.
      This probability can be estimated based on the number of previous miscarriages
      and maternal age.

PMID- 18714520
TI  - [Diagnostic image (382). A man with a painful knee and black cartilage].
AB  - A 56-year-old man presented with a painful knee with black pigmentation of
      synovium and cartilage due to ochronosis caused by alkaptonuria.

PMID- 18714521
TI  - [The formation of infliximab and anti-infliximab immune complexes as an
      explanation for non-responding to infliximab treatment of rheumatoid arthritis:
      observational study in 4 patients].
AB  - OBJECTIVE: To investigate the in vivo mechanism of non-responding to infliximab
      treatment of patients with rheumatoid arthritis (RA) and the role of anti
      infliximab antibodies by using radiolabeled infliximab. DESIGN: Descriptive and
      comparative study. METHOD: Two responding and two non-responding RA patients were
      infused with radiolabeled infliximab. Subsequently imaging investigations and
      serum analysis were performed at set times. RESULTS: The scintigrams showed that
      the labelled infliximab was mainly present in the blood until 24 h after
      infusion. There was a trend of faster blood clearance and higher liver and spleen
      uptake of 99mTc-infliximab in one non-responding patient. Labelled infliximab was
      taken up by inflamed joints. The anti-infliximab level was high (1008 and 1641
      U/ml) in the non-responders and low or not detectable in the responders. Sucrose
      gradients of serum revealed antibody complexes in both non-responders. Various
      sizes of antibody complexes, including very large ones, were observed in one non
      responder who developed a serious infusion reaction. CONCLUSION: Infliximab-anti
      infliximab immune complexes were found to form in RA non-responders due to the
      presence of significant quantities of anti-infliximab. This finding may partly
      explain the failure of the infliximab treatment.

PMID- 18714522
TI  - [Short-chain acyl-CoA dehydrogenase deficiency (SCADD): relatively high
      prevalence in the Netherlands and strongly variable fenotype; neonatal screening
      not indicated].
AB  - OBJECTIVE: To describe the clinical, genetic, and biochemical characteristics of
      short-chain acyl-CoA dehydrogenase deficiency (SCADD), a clinically heterogeneous
      metabolic disorder for which neonates are screened for in parts of the United
      States and Australia. To explore the genotype-phenotype relation and to discuss
      neonatal screening for SCADD. DESIGN: Retrospective study of 31 Dutch SCADD
      patients and 8 SCADD relatives. METHOD: Patients and relatives were included
      ifbiochemical SCADD characteristics (increased C4-carnitine and/or ethylmalonic
      acid) were present in combination with a mutation and/or the c.511C>T or c.625G>A
      variant on each SCAD-encoding (ACADS) allele. The patients were subdivided into 3
      genotype groups: mutation/mutation, mutation/variant and variant/variant group.
      RESULTS: A birth prevalence for SCADD of at least 1:50,000 was calculated. Most
      patients presented before the age of 3 years, mainly with developmental delay,
      epilepsy, behavioural disturbances and/or hypoglycaemia. The ACADS genotype
      showed a statistically significant association with biochemical, but not with
      clinical characteristics. In total 7 out of 8 SCADD relatives were free of
      symptoms. In 5 of the 31 patients, of whom 2 had severe symptoms, a second
      diagnosis was made which might explain the symptoms. CONCLUSION: SCADD was far
      more common than had previously been assumed and clinical symptoms in SCADD were
      non-specific, often transient or absent and not correlated with specific ACADS
      genotypes. SCADD does not meet major neonatal screening criteria and is therefore
      not suited for inclusion in neonatal screening programmes.

PMID- 18714523
TI  - [Percutaneous vertebroplasty for vertebral fractures caused by multiple myeloma,
      an aggressive vertebral haemangioma and in a traumatic burst fracture].
AB  - Percutaneous vertebroplasty (PVP) using polymethylmethacrylate bone cement is
      frequently used in the treatment of painful osteoporotic vertebral compression
      fractures in the Netherlands. In three patients there was another indication. A
      44-year-old woman suffering from vertebral pain due to an osteolytic lesion
      caused by multiple myeloma was treated with vertebroplasty of 4 vertebral levels.
      A 60-year-old woman with progressive complaints of back pain due to an aggressive
      vertebral haemangioma was treated with vertebroplasty after embolisation had only
      been partially successful. Lastly, a 50-year-old non-osteoporotic man with back
      pain persisting for six weeks due to a stable traumatic burst fracture of TIX
      could not be treated with standard care, i.e. corset and analgesics, because of
      obesity. He was treated with PVP after a cavity had been created in the vertebral
      corpus. Vertebroplasty is a minimal invasive procedure resulting in most patients
      in rapid diminishment of the pain caused by pathological vertebral fractures,
      which may be present for a longer period and may have different causes. The
      indication triad for vertebroplasty consists of localised back pain, pain when
      pressure is applied to the processus spinosus of the fractured level and MRI bone
      oedema, findings suggestive of microfractures in a pathologically changed
      vertebral body. The procedure is also suitable in patients with extensive
      comorbidity or a short life expectancy.

PMID- 18714524
TI  - [Determining the thyroid hormones T3 and T4 in the urine: an unreliable test for
      hypothyroidism].

PMID- 18714525
TI  - [International medical graduates in Dutch health care: the new assessment
      procedure].

PMID- 18714526
TI  - [Clinical reasoning and decision-making in practice. A man with swelling of both
      corners of the jaw].

PMID- 18714527
TI  - [Diagnostic image (373). A woman with a wrist injury].

PMID- 18714528
TI  - [Limited predictive value of diagnostic tests for outcomes following pelvic floor
      physiotherapy in patients with faecal incontinence].

PMID- 18714529
TI  - Coexistence of asthma and allergic rhinitis in adult patients attending allergy
      clinics: ONEAIR study.
AB  - BACKGROUND: Several studies have shown links between the upper and lower airways
      in allergic patients. OBJECTIVES: This study aimed to evaluate the prevalence of
      rhinitis in patients with allergic asthma attending allergy outpatient clinics
      and to examine the interrelationship between both conditions. METHODS: An
      epidemiological prospective study was carried out during the period 2004-2005 and
      170 allergists from all over the country participated. After obtaining written
      informed consent, we collected clinical and demographic data, a personal and
      family history of allergic diseases, and data on the duration and severity of
      asthma and rhinitis. These data were classified according to the criteria of the
      Global Initiative for Asthma and the Allergic Rhinitis and its Impact on Asthma
      guidelines, respectively. RESULTS: A total of 968 subjects were screened and 942
      were enrolled in the study. Mean (SD) age was 35.5 (14) years and 63% were
      female. Of these patients, 89.5% presented with allergic rhinitis. The duration
      of the disease was 12.6 (8.9) years for rhinitis and 11.4 (9.6) years for asthma
      (P < .0001). The severity of asthma was classified as intermittent (39%), mild
      persistent (30%), moderate persistent (27%), and severe persistent (4%). Rhinitis
      was classified as mild intermittent (24%), moderate/severe intermittent (22%),
      mild persistent (19%) and moderate/severe persistent (35%). A significant
      correlation was found (P < .0001) between the severity of rhinitis and asthma.
      The prevalence of allergic rhinitis was inversely correlated with the age of the
      patients (P < .0001) and the severity of asthma (P < .05). CONCLUSION: This study
      reinforces the high prevalence of allergic rhinitis in patients with asthma,
      which can affect as many as 89.5%.

PMID- 18714530
TI  - (CCTTT)n polymorphism of NOS2A in nasal polyposis and asthma: a case-control
      study.
AB  - BACKGROUND: Nitric Oxide (NO) has been proposed as an important signaling
      molecule. NO produced by the inducible NO synthase enzyme NOS2A is generated at
      high levels in certain types of inflammation. A pentanucleotide polypyrimidine
      microsatellite CCTTT has been identified in the promoter region of the NOS2A
      gene. OBJECTIVE: The aim of this study was to analyze the (CCTTT)n polymorphism
      in patients with asthma and nasal polyposis. MATERIAL AND METHODS: The study
      included 292 white individuals (194 patients and 98 controls). Asthma was
      diagnosed according to American Thoracic Society criteria and classified in
      accordance with the guidelines of the Global Initiative for Asthma. Skin prick
      tests were performed in all individuals. The polymorphism was analyzed by an
      electrophoretic method and by direct sequencing. RESULTS: A significant
      association was detected for a 15-repeat cutoff in nasal polyposis (Fisher P
      value = .0001, Monte Carlo P value [after 10(4) simulations] = .002).
      Multivariate analysis adjusted for age and sex confirmed this association with an
      increased risk of nasal polyposis (odds ratio, 14.39; 95% confidence interval,
      3.02-68.60; P = .001). CONCLUSION: The number of CCTTT repeats in the promoter
      region of NOS2A could be associated with the inflammatory process of nasal
      polyposis in our population. Modifications of NOS2A transcription levels could be
      involved in this association.

PMID- 18714531
TI  - Emedastine difumarate inhibits histamine-induced collagen synthesis in dermal
      fibroblasts.
AB  - BACKGROUND: Mast cell-derived histamine is known to act on dermal fibroblasts and
      contribute to formation of an intractable chronic allergic dermatitis. Although
      this fibrotic event may also occur in other organs such as the nasal mucosa, no
      direct evidence has been reported as to whether responsiveness to histamine by
      fibroblasts derived from different organs is of the same intensity. Furthermore,
      while type 1 histamine receptor (H1R) blockers have been shown to be effective
      for alleviation of the symptoms of allergic diseases, their ability to affect
      histamine-induced tissue remodeling has not yet been clarified. OBJECTIVE: Our
      aim was to study the effect of H1R-blockers on histamine-induced tissue
      remodeling. METHODS: A macroarray assay was used for a comprehensive analysis of
      histamine-induced gene expression by normal human fibroblasts. Fibroblasts
      derived from skin or nasal mucosa were cultured in the presence of various
      concentrations of histamine, and the synthesis of type 1 collagen was measured by
      means of semi-quantitative reverse-transcriptase polymerase chain reaction and
      enzyme-linked immunosorbent assay. To determine the effect of H1R blockers,
      diphenhydramine hydrochloride and emedastine difumarate were investigated in this
      assay. RESULTS: Histamine induced expression of various kinds of fibrogenic
      molecules in fibroblasts. Increased type 1 collagen expression was observed in
      fibroblasts treated with high-dose (0.1 mM to 1 microM) and low-dose (1 pM)
      histamine. This histamine-induced type 1 collagen synthesis was effectively
      diminished by emedastine difumarate. While organ specificity seems to be
      involved, emedastine difumarate is considered to be an effective drug for
      reversal of such histamine-induced remodeling in the skin. CONCLUSIONS: We found
      that the expression of fibroblast-derived genes is differentially regulated by
      different concentrations of histamine and that the robustness of the inhibitory
      action of H1R blockers is different for skin-derived and nasal mucosa-derived
      fibroblasts. We believe that our findings may contribute to a better
      understanding of the mechanisms of histamine-induced tissue remodeling and
      provide information useful for the management of refractory allergic dermatitis.

PMID- 18714532
TI  - Immediate and cell-mediated reactions in parasitic infections by Anisakis
      simplex.
AB  - BACKGROUND: Anisakis simplex is responsible for allergic symptoms after repeated
      ingestion or contact with parasitized fish. OBJECTIVE: To further analyze type I
      and IV immunologic mechanisms in a group of patients with allergic reactions to A
      simplex, we performed prick-by-prick testing with A simplex larvae and patch
      tests with live, cooked, or frozen larvae of the A simplex parasite. METHODS:
      Thirty-eight patients underwent skin prick test and radioallergosorbent test with
      inhalant allergens, foods, and A simplex. Prick-by-prick tests with A simplex and
      patch tests with live, cooked, and frozen larvae were carried out in 10 patients
      with evidence of allergy to A simplex. RESULTS: Prick-by-prick testing yielded a
      positive result in 100% of cases with live larvae and in 70% with cooked and
      frozen larvae. Patch tests with A simplex were positive in 8 patients for live
      larvae, in 3 patients for frozen larvae, and in 1 patient for cooked larvae.
      CONCLUSION: Our data emphasize that A simplex is responsible for both immediate
      allergic reactions and cell-mediated (delayed) reactions, in particular in
      subjects with occupational exposure. In addition, our data demonstrate that not
      only live but also frozen and cooked larvae can induce sensitization. This
      observation may be explained by differences in the allergenic proteins involved,
      and further studies will be required to address this possibility.

PMID- 18714533
TI  - Clinical and immunologic features of pediatric patients with common variable
      immunodeficiency and respiratory complications.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is the term used to describe
      a heterogeneous group of B-cell deficiency syndromes characterized by
      hypogammaglobulinemia, impaired antibody production, and recurrent bacterial
      infections. OBJECTIVES: To determine the clinical manifestations and perform an
      immunological analysis of pediatric CVID patients suffering from respiratory
      complications. METHODS: The records of 10 patients with CVID who were followed up
      from 1992 to 2005 (6 males and 4 females) with a median (interquartile range) age
      of 13.9 (10.4-19.4) years were reviewed. All patients met the standard criteria
      set for CVID. RESULTS: Median total serum levels of immunoglobulin (Ig) G, IgM,
      and IgA in mg/dL were 383.5 (239.2-574.5), 32.5 (17.0-117.0), and 12.5 (5.0
      30.7), respectively. Median age at the onset of symptoms, at CVID diagnosis, and
      on starting intravenous Ig therapy was 4.0 (0.8-6.2), 9.4 (6.7-11.3), and 9.1
      (7.0-11.6) years, respectively. Associated disorders were recurrent infections
      (100%), bronchiectasis (90%), and growth failure (80%), whereas malabsorption,
      malignant neoplasm, inflammatory bowel disease, and autoimmune disorders were
      less common. All bronchiectatic patients had a low percentage of B cells, with an
      average of 4% (range, 1%-7%). The characteristic computed tomography finding in
      patients with CVID was a multilobar pattern. Malignant neoplasm developed an
      average of 11.5 (range, 6.5-20.2) years after the diagnosis of CVID was made.
      CONCLUSION: Recurrent respiratory infection should be evaluated to rule out CVID.
      Early diagnosis and intravenous Ig replacement therapy may reduce the frequency
      of respiratory infection. Low levels of serum Ig and percentage of B lymphocytes
      at diagnosis are important parameters for identifying patients at risk of
      structural lung damage.

PMID- 18714534
TI  - Alterations in humoral immunity in relatives of patients with common variable
      immunodeficiency.
AB  - BACKGROUND AND OBJECTIVES: It has been reported that there is a high prevalence
      of immunodeficiency and autoimmunity in relatives of patients with common
      variable immunodeficiency (CVID). The aim of this study was to determine the
      prevalence of immunoglobulin deficiency in relatives of patients with CVID in
      Iran, where there is a high rate of consanguineous marriage. METHODS: A
      descriptive study was undertaken in 64 family members of 23 unrelated CVID
      patients. The group contained 17 fathers, 18 mothers, 18 sisters, 9 brothers, and
      2 children. Serum immunoglobulin levels were measured by nephelometry.
      Immunoglobulin (Ig) G subclass levels were measured in a subgroup of 36
      individuals. Serum IgA levels were confirmed by enzyme-linked immunosorbent assay
      for subjects with suspected IgA deficiency. RESULTS: The rate of consanguineous
      marriage in families containing relatives with antibody deficiencies was
      significantly higher than in those families in whom relatives did not have immune
      deficiencies. IgA deficiency was observed in 2 relatives of patients with CVID.
      Also CVID was observed in 2 family members. In 3 fathers and 1 brother, IgM
      levels were lower than normal. Three relatives had IgG4 deficiency and 1 person
      had combined IgG4 and IgG2 deficiency. Twenty percent of the relatives had
      hypogammaglobulinemia (including IgA deficiency, CVID, decreased levels of IgM,
      and IgG subclass deficiencies). CONCLUSION: In our study, alteration in humoral
      immunity in relatives of CVID patients was higher than previously reported, and
      this could be attributed to the high rate of consanguineous marriage in Iran.
      Since the family members of CVID patients are at high risk of
      hypogammaglobulinemia, it is advisable that they be evaluated for
      immunodeficiency disorders and monitored throughout their lifetimes.

PMID- 18714535
TI  - Soluble CD40 ligand and soluble P-selectin in allergic asthma patients during
      exercise-induced bronchoconstriction.
AB  - BACKGROUND: The interactions between CD40 and its ligand, CD40L, control humoral
      and cell-mediated immune responses. CD40 ligation may promote asthma-associated
      inflammatory responses in the airways. Many reports confirm the inflammatory
      basis of exercise-induced bronchoconstriction (EIB) in asthmatics. METHODS: The
      study was conducted in a group of 19 asthmatic patients (11 with EIB, 8 without
      EIB) and 8 healthy volunteers. We analyzed the changes in plasma concentrations
      of soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin) induced by
      intensive exercise. We also studied possible correlations with the results of
      measurements commonly associated with asthmatic inflammation. RESULTS: The study
      revealed statistically significant higher baseline concentrations of sCD40L--but
      not sP-selectin--in the group of asthmatics with EIB than in those without. In
      the asthmatic patients with EIB, sCD40L and sP-selectin concentrations increased
      significantly 30 minutes after exercise and returned to baseline 24 hours after
      exercise. Baseline concentrations of sCD40L correlated with baseline sP-selectin
      or fractional exhaled nitric oxide concentration (FE(NO)), an increase in sP
      selectin 30 minutes after exercise, and changes in FE(NO) or bronchial
      hyperresponsiveness 24 hours after exercise. A statistically significant
      correlation between an increase in sCD40L concentrations 30 minutes after
      exercise and an increase in FE(NO) 24 hours after exercise or baseline eosinophil
      cationic protein was observed. CONCLUSION: After exercise in the group of
      allergic asthmatics with EIB, upregulation of CD40L by increased expression of
      inflammatory molecules and improved sensitivity of CD40-responsive cell types to
      the effects of proinflammatory cytokines may play an important role in the
      increased airway inflammation observed after postexercise bronchoconstriction.

PMID- 18714536
TI  - CD30 serum levels and response to hymenoptera venom immunotherapy.
AB  - BACKGROUND: The glycoprotein CD30 is expressed and released by T lymphocytes that
      secrete type 2 helper cytokines of (T(H)2). These molecules play a role in the
      pathogenesis of allergic diseases. Venom immunotherapy has proven to be very
      effective in hymenoptera venom allergy through a shift in cytokine production
      from T(H)2-type cytokines to T(H)1-type cytokines. OBJECTIVE: To evaluate the
      relationship between the soluble form of CD30 (sCD30) and venom immunotherapy in
      patients with hymenoptera venom allergy. MATERIALS AND METHODS: sCD30 levels were
      assayed by enzyme-linked immunosorbent assay in the sera of 61 healthy controls
      and 14 patients with hymenoptera venom allergy who had undergone immunotherapy
      before treatment and 1,3, and 12 months after treatment started. Nine patients
      were allergic to Apis venom, 4 to Vespula venom, and 1 to Polistes venom.
      RESULTS: CD30 serum levels (median, interquartile range) were significantly
      higher in venom-allergic patients before treatment (33.6 U/mL; 14.8-61.6) than in
      controls (9.7 U/mL, 1.9-21.3) (P < .000). These levels decreased progressively
      during treatment in all patients except 2 (P < .000). At the third month of
      therapy, the levels reached statistical significance in comparison with baseline.
      CONCLUSIONS: This study shows that sCD30 levels are significantly higher in
      patients with hymenoptera venom allergy and indirectly confirms a preferential
      T(H)2-type cytokine production in these patients. sCD30 expression decreases
      during immunotherapy, thus confirming the immunomodulatory role of this treatment
      in promoting a shift to T(H)1-type cytokines.

PMID- 18714537
TI  - Analysis of -675 4 g/5 G SERPINE1 and C-159T CD14 polymorphisms in house dust
      mite-allergic asthma patients.
AB  - BACKGROUND: Experimental studies indicate that endogenous plasminogen activator
      inhibitor-1 (PAI-1, encoded by the gene SERPINE1) modulates the immune response
      to lipopolysaccharide (LPS). On the other hand, LPS induces PAI-1 secretion.
      Activation of individual cells by LPS is facilitated by CD14. The single
      nucleotide polymorphisms -675 4G/5G in SERPINE1 and C-159T in CD14 are major
      determinants of PAI-1 and CD14 expression, respectively. OBJECTIVE: To evaluate
      the frequency of the -675 4G/5G SERPINE1 and C-159T CD14 polymorphisms in house
      dust mite (HDM) allergic asthma patients. METHODS: The polymorphisms were
      evaluated in unrelated inhabitants of northeastern Poland, including 372 HDM
      allergic asthmatic patients and 160 healthy nonatopic control subjects using
      polymerase chain reaction. RESULTS: Both the C allele of CD14 and the 4G allele
      of SERPINE1 were more frequently encountered in HDM-allergic asthmatic patients
      than in healthy control individuals. When the 5G/5G-TT/CT genotype was considered
      as a nonrisk genotype, all other genotypes were associated with asthma. The odds
      ratios ranged from 3.96 (95% confidence interval, 1.56-10.1) for the 5G/5G-CC
      genotype to 10.7 (95% confidence interval, 5.1-24.9) for the 4G/4G-CC genotype.
      Bronchial reactivity to histamine and total serum immunoglobulin (Ig) E levels
      were predominantly associated with the 4G/5G SERPINE1 variants, while bronchial
      reactivity to Dermatophagoides pteronyssinus and serum concentrations of specific
      IgE against D pteronyssinus were predominantly associated with the C/T CD14
      variants. Patients with 4G/4G-CC genotype had the lowest forced expiratory volume
      in 1 second and the highest bronchial reactivity. CONCLUSION: The SERPINE1 and
      CD14 polymorphisms studied here are associated with different aspects of
      bronchial reactivity and IgE response. Our results indicate that PAl-1 and CD14
      may interact to affect susceptibility to allergic asthma.

PMID- 18714538
TI  - Activation of basophils by stem cell factor: comparison with insulin-like growth
      factor-I.
AB  - BACKGROUND: Basophils are an active participant in the pathogenesis of local
      inflammation in allergic diseases such as asthma, but it is not fully known how
      basophil activation is regulated in inflamed tissue. OBJECTIVE: In order to
      clarify the control mechanisms of basophil activation in chronic inflammation and
      at remodeling sites, we analyzed the effects of fibroblast-derived cytokines,
      stem cell factor (SCF), and insulin-like growth factor-I (IGF-I) on basophils.
      METHODS: The effects of SCF and IGF-I on degranulation and surface activation
      marker expression by basophils were assessed and compared. RESULTS: SCF enhanced
      human basophil histamine release elicited by some, but not all, secretagogues;
      degranulation in response to IgE- or FcepsilonRI-mediated stimulation and 12-o
      tetradecanoyl-phorbol-13-acetate (TPA) was enhanced by SCF. SCF slightly enhanced
      ionophore A23187-induced histamine release by basophils from some donors, but it
      failed to affect the release elicited by monocyte chemoattractant protein-1 (MCP
      1), formylmethionyl-leucyl-phenylalanine (FMLP) or C5a. The repertoire of
      secretagogues responsive to SCF was similar to that of IGF-I. Expression levels
      of both CD11b and CD69 markers were significantly enhanced by the combination of
      SCF and IGF-I. CONCLUSIONS: These results suggest that SCF and IGF-I may modify
      the activation of basophils in a similar and/or synergistic fashion. Interaction
      of basophils with these cytokines might be involved in the pathogenesis of local
      inflammation and the remodeling process in asthma.

PMID- 18714539
TI  - Asthma and allergic rhinitis in a patient with BTK deficiency.
AB  - BTK deficiency is a primary immunodeficiency disease characterized by the absence
      of circulating B cells and agammaglobulinemia. While recurrent bacterial
      infections are the most common manifestations, symptoms of allergy and asthma are
      rare. We present the case of a 7-year-old boy who presented with asthma symptoms,
      allergic rhinitis, and severe papular urticaria. He had a positive skin prick
      test to aeroallergens and food allergens. However, further laboratory tests
      revealed a low number of B cells and decreased serum levels of all immunoglobulin
      isotypes. Molecular analysis revealed a mutation in the BTK gene. Although
      patients with BTK deficiency seem to be protected from atopy, our patient had
      allergic symptoms suggesting a bias toward a type 2 helper T cell pattern in this
      case. Primary antibody deficiency should be considered in the differential
      diagnosis of pediatric allergy and asthma when respiratory infection persists
      despite appropriate treatment.

PMID- 18714540
TI  - Anaphylaxis to oral iron salts. desensitization protocol for tolerance induction.
AB  - Allergies to iron salts are seldom reported. We studied a patient with iron
      deficiency anemia who had suffered anaphylactic reactions caused by oral iron
      salts. An allergy study was performed using single-blind, placebo-controlled oral
      challenge and skin tests with various iron salts as well as excipients in
      commercial formulations. Oral challenges were positive for 2 of the commercial
      formulations of iron salts. Intradermal tests with ferrous sulphate and ferrous
      lactate also showed positive results. All of the cutaneous tests using the
      excipients were negative. A desensitization protocol was designed which enabled
      us to readminister ferrous sulphate, although antihistamines were necessary to
      guarantee good tolerance to iron salts. We report a patient with allergy to iron
      salts, positive skin tests, and positive controlled challenge. We highlight the
      desensitization protocol designed to complete the therapeutic management of the
      anemia.

PMID- 18714541
TI  - Desensitization to co-trimoxazole in a patient with fixed drug eruption.
AB  - Although co-trimoxazole is a major cause of fixed drug eruption, there are no
      reports in the literature of desensitization protocols for co-trimoxazole in such
      patients. We present the case of an 85-year-old woman with a fixed drug eruption
      to co-trimoxazole. Since she needed co-trimoxazole therapy for treatment of
      infection of a prosthetic hip by Staphylococcus aureus, she underwent allergy
      testing with co-trimoxazole and its components sulfamethoxazole and trimethoprim.
      Allergy tests were all negative and a diagnosis of nonallergic hypersensitivity
      reaction to co-trimoxazole was made. Based on previous experience, we decided to
      attempt a desensitization protocol with co-trimoxazole. After 10 days, the
      patient could receive 800 mg of sulfamethoxazole and 160 mg of trimethoprim twice
      a day and no adverse reactions were observed. We suggest that desensitization
      protocols with co-trimoxazole be considered in patients with fixed drug eruption,
      especially when there are no alternative drugs.

PMID- 18714542
TI  - Food-dependent exercise-induced anaphylaxis: possible impact of increased
      basophil histamine releasability in hyperosmolar conditions.
AB  - We present a case of anaphylactic shock induced by exercise following celery
      ingestion. The possible mechanism of food-dependent exercise-induced anaphylaxis
      (FDEIA) and the laboratory tests for its diagnosis are discussed. We evaluated
      spontaneous, celery-allergen-induced, and anti-FcepsilonRI-antibody-induced
      histamine release from basophils obtained from the patient, 2 celery-allergic
      controls, and 3 healthy controls. Buffers of increasing osmolarity were used to
      mimic conditions of vigorous physical exercise. Only the patient's basophils
      showed an increase in spontaneous, anti-FcepsilonRI antibody-induced and allergen
      induced histamine release under physiological conditions and with slightly
      increased medium osmolarity. To our knowledge, this is the first report on the
      possible role of increased histamine releasability in the pathogenic mechanism of
      FDEIA. We suggest that FDEIA results from increased histamine releasability
      triggered by physical effort after exposure to a sensitizing food allergen.

PMID- 18714543
TI  - Diurnal variation of nasal nitric oxide levels in healthy subjects.

PMID- 18714544
TI  - Late patch test reaction to dichlorophene.

PMID- 18714545
TI  - Tolerability of lumiracoxib in patients with analgesic intolerance.

PMID- 18714546
TI  - Allergen-specific IgE to inhalant and food allergens and total IgE values in
      China: comparison of 2 commercial immunoassays.

PMID- 18714547
TI  - Wasp venom-specific IgE: towards a new decision threshold?

PMID- 18714548
TI  - Bullying: a global public health risk.

PMID- 18714549
TI  - Concepts of bullying: developmental and cultural aspects.
AB  - This review considers the origins of the term bullying and historical changes in
      the definition of bullying, leading to contemporary research definitions in terms
      of agreed criteria. The paper next considers how we can assess the actual working
      definitions or criteria used by pupils, teachers, parents or others concerned
      with bullying; in different countries. Developmental changes in the understanding
      of bullying are reviewed and contrasted with developmental changes in bullying
      behavior. In the final section, cultural similarities and differences are
      reviewed. Again, two aspects are considered--the words used for bullying-related
      phenomena in different countries, their meaning, and the behavioral
      manifestations of bullying.

PMID- 18714550
TI  - The development of bullying.
AB  - Over the past 25 years, concern has been growing for children's bullying. We now
      recognize that bullying is wrong and hurtful. Research has fuelled a growing
      understanding that persistent bullying may be an indication of significant psycho
      social problems. In this paper, we describe our longitudinal research on the
      development of bullying, examine risk factors associated with diverse pathways of
      bullying, and consider intervention strategies to address problems among children
      and youth who bully.

PMID- 18714551
TI  - Psychiatric conditions associated with bullying.
AB  - Bullying is a complex phenomenon moderated not only by the personal
      characteristics and behavioral traits of the individual but also by family
      rearing practices, as well as by situational factors such as the frequency and
      type of bullying. The phenomenon is also affected by group processes among the
      individuals present during the event. Bullying is a distressing experience that
      is often continuous over years and predicts both concurrent and future
      psychiatric symptoms and disorders, even in adulthood. At young ages, attention
      deficit hyperactivity disorder and depression, as well as anxiety, are prevalent
      concurrently with bullying among the children involved. Later in young adulthood,
      male victims are at risk for anxiety, male bullies for personality disorders, and
      male bully-victims for both personality disorders and anxiety, and the risk is
      especially increased if the child is disturbed when involved in bullying at
      school age. Rarely does any single behavior predict future problems as clearly as
      bullying does, and additional assessment of psychiatric problems is always
      warranted, if the child is involved in bullying as a bully, victim or bully
      victim. Based on our current knowledge, school-based interventions regulating the
      behavior of the child, increasing pro-social skills and promoting peer
      relationships are recommended for those without concurrent psychiatric
      disturbance, but those displaying psychiatric symptoms and disorders should be
      referred for psychiatric consultation and intervention.

PMID- 18714552
TI  - Bullying and suicide. A review.
AB  - Being a victim or perpetrator of school bullying, the most common type of school
      violence, has been frequently associated with a broad spectrum of behavioral,
      emotional, and social problems. Suicide is third leading cause of mortality in
      children and adolescent in the United States of America and around the world.
      This paper provides a systematic review of the previous 37 studies conducted in
      children and adolescents from communities, as well as in special populations that
      examined the association between bullying experiences and suicide, with an
      emphasis on the strengths and limitations of the study designs. Despite
      methodological and other differences and limitations, it is increasingly clear
      that any participation in bullying increases the risk of suicidal ideations
      and/or behaviors in a broad spectrum of youth.

PMID- 18714553
TI  - Peer harassment and disordered eating.
AB  - In this paper, we review existing literature regarding peer harassment and its
      association with a range of weight-related attitudes and behaviors. We
      conceptualize peer harassment to include traditionally defined bullying behavior,
      other social and relational forms of bullying, as well as teasing and other
      verbal harassment. Weight-based teasing is particularly relevant to weight
      related issues and has been associated with clinical eating disorders, unhealthy
      weight control behaviors, and weight-related attitudes, such as body
      dissatisfaction. Studies using both clinical samples of eating disorder patients
      and general samples of college students or adolescents have demonstrated these
      relations. Emerging issues in this field, including teasing by family members,
      research with males, teasing and weight-related issues in developing countries,
      and the measurement of teasing experience are also discussed. Interventions with
      healthcare providers, parents, school personnel, and policy can contribute to the
      prevention of teasing and its associated weight-related attitudes and behaviors.

PMID- 18714554
TI  - Interventions to reduce bullying.
AB  - Recognizing the potential heath risk of bullying in schools, numerous anti
      bullying interventions have been developed. These measures have been designed to
      prevent bullying from happening and/or to stop bullying from continuing once it
      has occurred. Evaluations of the effectiveness of such interventions indicate
      several positive effects in reducing the level of bullying in schools and in
      stopping cases from continuing. Alternative approaches and intervention methods
      are reviewed and their reported effectiveness examined. Factors considered
      relevant in the choice of method are discussed, such as the severity of the
      bullying, the age of the child and the thoroughness of program implementation.

PMID- 18714555
TI  - Prevention of public health risks linked to bullying: a need for a whole
      community approach.
AB  - Bullying is a very toxic psychosocial stressor associated with serious health
      problems and death, affecting both the victims and the bullies. This form of
      abuse or maltreatment occurs around the world and along the lifespan. Health
      professionals have the unique responsibility of promoting the development of
      community initiatives for the prevention of bullying and related health problems.
      This effort must include ongoing programs with elements of primary, secondary,
      and tertiary prevention. These programs should be supported and monitored by a
      public health policy with a strategy aimed at developing a whole community
      awareness about bullying and the related health risks, prohibiting bullying, and
      developing emotionally and physically safe environments in schools and workplace
      settings. Public health policy should mandate the monitoring, detection, and
      reporting of bullying incidents; provide guidance for school intervention; and
      offer guidelines for medical consultation.

PMID- 18714556
TI  - Peer victimization and intentional injuries: quantitative and qualitative
      accounts of injurious physical interactions between students.
AB  - Studies have shown that peer victimization engenders physical injuries both
      indirectly (i.e. as a trigger of injurious events) and directly (i.e. through
      intentional physical harm). How those injuries occur has not been much
      researched. OBJECTIVE: To highlight the various circumstances in which injuries
      are sustained by young teenagers when physically interacting with other students,
      and to characterize more specifically the context surrounding those injuries
      sustained resulting from violent actions. METHOD: Data were extracted from
      information already available from structured interviews conducted during two
      consecutive school years with children aged 10-15 years who had been hospitalized
      due to injury and who were residing in Stockholm County (Sweden) (n = 634). The
      current study considers those injuries resulting from physical interactions
      between students and pays attention to the gender and age distribution of the
      victims. The free text descriptions of the "interaction" injuries resulting from
      violent actions were re-read and examined by means of content analysis. RESULTS:
      Of the injuries reported, 23.5% resulted from physical interactions between
      students. The most frequent context of their occurrence was sports and play.
      Other injuries resulted either from assaults where the victim was in a clear
      imbalance of power (n = 24) or from violent incidents in which the victim was not
      powerless (n = 27). The two latter situations were much more common among boys.
      CONCLUSION: Peer victimization has an impact on children's safety both within and
      outside the school arena. Students are injured by their peers not only from
      deliberate violence targeting them but also from violent physical interactions in
      which they play an active role. These injurious events have a clear gender and
      age component.

PMID- 18714557
TI  - Bullying victimization among 13 to 15-year-old school children: results from two
      comparative studies in 66 countries and regions.
AB  - AIM: to examine the prevalence of bullying victimization in 66 countries and
      territories from five continents based on data from two large international
      surveys: the 2001/2 Health Behavior in School-aged Children survey (HBSC) and the
      Global School-based Students Health Survey (GSHS). The surveys provide nationally
      representative, cross-sectional information on 13-15-year-old school children (N
      = 218,104). OUTCOME MEASURES: Bullying victimization, once or more within the
      past 2 months (HBSC)/30 days (GSHS). RESULTS: On average, 32.1% of the children
      were bullied at school at least once within the past 2 months in countries
      involved in the HBSC study and 37.4% of children were bullied at least one day
      within the past 30 days in countries involved in the GSHS study. In both surveys,
      a large variation in prevalence was found across countries. The lowest prevalence
      in the GSHS survey was observed in Tajikistan (7.1% for both boys and girls) and
      among HBSC countries in Sweden (16.0% for boys and 14.6% for girls) and the Czech
      Republic (17.1% for boys and 14.2% for girls). The highest prevalence for boys in
      the GSHS survey was found in Zimbabwe (Bulawayo) (70.2%) and for girls in Zambia
      (67.1%). In the HBSC survey, Lithuania had the highest prevalence of bullying
      victimization (62.7% for boys and 64.4% for girls). CONCLUSION: Victimization to
      bullying violates the fundamental rights of children; our study suggests that
      although many countries signed the United Nations Convention on the Rights of the
      Child, many have to work harder to fulfill the goals of the Convention.

PMID- 18714558
TI  - Public health, safety and educational risks associated with bullying behaviors in
      American adolescents.
AB  - Based on a national representative sample of United States (US) middle and high
      school students, we studied the association between different health, safety, and
      educational risk factors and involvement in a variety of bullying behaviors.
      DESIGN: Based on an analysis of US data of the 1996 World Health Organization
      Health Behavior in School-aged Children survey, with cross-sectional survey
      information on 9,938 students in grades 6 through 10. RESULTS: Thirty-nine per
      cent of the students were involved in bullying others and/or were victims of
      bullies at least three times in the preceding 12 months. Bullies, victims, and
      those who are both, are at a significantly higher risk of suffering from self
      inflicted, accidental, and perpetrated injuries, abusing-over-the counter
      medications, hurting animals and people on purpose, using a weapon that could
      seriously hurt someone, and being frequently absent from school, as compared with
      their peers who are not involved in bullying or rarely participated in it. Those
      students who are both bullies and victims experience a wide array of associated
      risk behaviors with odd ratios stretching from 1.54 to 14.17. CONCLUSIONS: The
      present study confirmed that participation in bullying behaviors, as a bully or
      as a victim, is associated with multiple health, safety, and educational hazards.
      Students who are bullies and/or victims are at a high risk of dying from self
      inflicted, accidental, or perpetrated injuries.

PMID- 18714559
TI  - Deaths linked to bullying and hazing.
AB  - The purpose of this study was to determine the extent of news reports of deaths
      associated with bullying and hazing among young people over a period of 57 years.
      This study was based on a survey of death events linked to bullying or hazing
      reported in English newspapers from January 1, 1950 through December 31, 2007.
      The search was based on the review of major United States and world publications,
      written in English, using the terms "bullying, hazing, ragging, and death." In
      the last 57 years, at least 250 reported cases of deaths were linked to bullying,
      hazing, or ragging, reported in English language newspapers from around the
      world. Of these news stories (n = 121), 76% contained an alleged history that the
      victim was bullied. Twenty-two per cent (n = 55) of these reports were associated
      with suspected hazing or ragging. In only four cases (2%), those who died had a
      history of bullying others. The majority of the reports of bullying related
      deaths (62.3%) originated in Europe, with most of them (93%) occurring in the
      United Kingdom. Sixty-seven percent of bullying-related deaths were reported
      during the last 10 years. CONCLUSIONS: The significant increment in news reports
      concerning deaths associated with bullying may be the result of a rise in public
      awareness about the lethal aspects of this type of maltreatment. An urgent global
      public health need exists to ascertain the regional mortality prevalence related
      to bullying and hazing, along the lifespan.

PMID- 18714560
TI  - Technetium-99m-sestamibi scintigraphy in gynecological cancer imaging.
AB  - A new diagnostic method, technetium-99m-sestamibi scintigraphy, and its potential
      use in gynecological oncology is described. The biochemical mechanisms of uptake
      and retention of technetium-99m-sestamibi in neoplastic cells are presented and
      the grounds for the potential use of the tracer in predicting the response to
      first-line chemotherapy in ovarian cancer patients are discussed. Based on the
      available literature data and on our own studies, the sensitivity and specificity
      of technetium-99m-sestamibi scintigraphy in ovarian cancer diagnosis are
      assessed, and the current place of this method among other functional imaging
      methods applied in gynecological oncology is discussed. Technetium-99m-sestamibi
      scintigraphy seems to provide an attractive alternative method to the expensive
      PET imaging, and can be easily performed in most hospitals. However, further
      studies in a larger series of patients are necessary before this method is widely
      applied.

PMID- 18714561
TI  - Genetic polymorphisms, the metabolism of estrogens and breast cancer: a review.
AB  - Breast cancer is the most common female cancer and the second cause of cancer
      death in women. Despite recent breakthroughs, much of the etiology of this
      disease is unknown and the most important risk factor, i.e., exposure to
      endogenous and exogenous estrogen throughout life cannot explain the
      heterogeneity of prognosis nor clinical features of patients. Recently, many gene
      polymorphisms in the metabolism of breast cancer have been described as possible
      neoplasm etiologic factors. This review is an attempt to summarize the current
      knowledge about these polymorphisms and to determine new target genes for
      diagnosis and treatment of the disease. Polymorphisms in the genes CYP17, CYP19,
      CYP1A1, CYP1A2, CYP1B1, UGT1A1, SULT1A1, 17-hydroxysteroid-dehydrogenase, COMT,
      GST, ESR1, and ESR2 are described.

PMID- 18714562
TI  - Peri- and intratumoral T and B lymphocytic infiltration in breast cancer.
AB  - PURPOSE: To investigate peritumoral and intratumoral infiltrates in surgical
      specimens obtained from patients with invasive breast cancer, and of relating
      these to tumor size. METHODS: Twenty-six surgical specimens obtained from
      patients diagnosed with breast cancer underwent immunohistochemical preparation
      and CD3, CD8, CD20 and CD68 labeling. The positive cells were counted in the
      tissue samples and correlated with the tumor size determined by imaging methods
      (TIA < or = 2 or TIB > 2 cm). RESULTS: There was a significant reduction in
      intratumoral B lymphocytes (CD20+), although this reduction could only be
      observed in TIA. In relation to peritumoral T lymphocytes (CD3+), there was a
      significant reduction in TIB, in comparison with TIA. Peritumoral and
      intratumoral CD3+ and CD68+ presence in completely opposite ways in both sizes of
      tumors. CONCLUSION: Peritumoral and intratumoral infiltrates of T and B
      lymphocytes are different and depend on tumor size.

PMID- 18714563
TI  - Self-sampling for human papillomavirus (HPV) testing as cervical cancer screening
      option. Experience from the LAMS study.
AB  - PURPOSE: To compare Hybrid Capture II (HC2) in detecting high-risk (HR) HPV in
      patient-collected vaginal samples with those obtained using gynaecologist
      collected samples. METHODS: Patients were submitted to Pap smears, visual
      inspection with acetic acid (VIA) and HC2 for hr-HPV. RESULTS: A total of 1,081
      HC2 tests for HR-HPV were performed: 770 (71.2%) samples were collected by a
      physician and 311 (28.8%) were self-collected by the patients. In detecting any
      cervical lesion, the sensitivity of HC2 collected by a physician was higher
      (92.86%) than that (37.5%) in the self-sampling group. Negative predictive value
      (NPV) was high for both, 99.69% and 93.75%, respectively. Using the CIN2 cutoff,
      performance of HC2 was significantly improved: 92.9% and 62.5%, respectively. HC2
      specificity for any cervical lesion and for CIN2 or higher were close to 90% in
      both groups. CONCLUSIONS: Self-sampled HPV testing is a powerful option to
      increase the detection of cervical lesions in women segregated from prevention
      programs.

PMID- 18714564
TI  - Association study of vascular endothelial growth factor gene polymorphisms in
      endometrial carcinomas in a Japanese population.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) is one of the most potent
      endothelial cell mitogens and plays a critical role in angiogenesis of
      endometrial carcinomas. Several studies have demonstrated positive associations
      between VEGF gene polymorphisms and several carcinomas. In this study we
      investigated whether VEGF gene polymorphisms are associated with endometrial
      carcinomas in a Japanese population. METHODS: The allele frequencies and genotype
      distributions of VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms were
      examined in 105 endometrial carcinomas and 179 controls using PCR-RFLP analysis.
      An association of these polymorphisms with three-year disease-free survival was
      evaluated using the Kaplan-Meier method. RESULTS: No significant differences in
      the allele frequencies and genotype distributions of VEGF -460 C/T (p = 0.54,
      0.90), +405 G/C (p = 0.31, 0.17), and +936 C/T polymorphisms (p = 0.46, 0.24)
      were observed between endometrial carcinoma patients and controls. There were no
      significant differences in the frequencies of haplotype -460 T/+405 C between
      patients and controls. Futhermore, VEGF -460 C/T, +405 G/C, and +936 C/T
      polymorphisms were not associated with three-year disease-free survival of
      endometrial carcinoma patients. CONCLUSIONS: Although limited by sample size, our
      study did not demonstrated any evidence that VEGF -460 C/T, +405 G/C, and +936
      C/T polymorphisms are associated with an increased risk of endometrial carcinomas
      in Japanese women.

PMID- 18714565
TI  - HPV in men.
AB  - PURPOSE: To collect information about HPV in men and the (possible) correlation
      with HVP infection in women. METHODS: Review of the literature. RESULTS: An
      overview of HPV-related penile and anal malignancies in men and the risk factors
      of acquiring HPV. CONCLUSION: In men HPV is also partially responsible for
      anogenital malignancies. Although the prevalence of HPV-related malignancies in
      men is much lower than in women, it is useful to gain more knowlege. Especially
      knowing if men are really the HPV reservoir and transmitters for women can make a
      difference in deciding whether men should also be screened for HPV and if they
      are good candidates for vaccination.

PMID- 18714566
TI  - Stromal cells play a role in cervical cancer progression mediated by MMP-2
      protein.
AB  - Metalloproteinases, especially metalloproteinase-2 (MMP-2), are known for their
      role in the degradation of the extracellular matrix. Nevertheless, a thorough
      understanding of MMP-2 expression in neoplastic lesions of the uterine cervix has
      yet to be accomplished. This study aimed to analyze the MMP-2 expression in
      cervical intraepithelial neoplasia III (CIN3) and in cervical squamous cell
      carcinoma, in tumor cells and adjacent stromal cells. MMP-2 expression was
      assessed by an immunohistochemical technique. MMP-2 expression was greater in the
      stromal cells of invasive carcinomas than in CIN3 (p < 0.0001). MMP-2 expression
      in stromal cells correlates with the clinical stage, gradually increasing as the
      tumor progresses (p = 0.04). This study corroborates that stromal cells play an
      important role in tumor invasion and progression, mediated by the progressive
      enhancement of MMP-2 expression from CIN3 to advanced invasive tumor. The intense
      MMP-2 expression most probably is associated with poor tumor prognosis.

PMID- 18714567
TI  - Cost of screening and treatment of cervical dyskaryosis in Germany.
AB  - Human papillomavirus (HPV) infection is the principal cause of cervical cancer.
      Clinical trials with HPV vaccines have shown high efficacy against HPV-induced
      precancerous cervical lesions. Before implementing a vaccination programme, up-to
      date data on cervical dyskaryosis, incidence and annual treatment costs are
      needed. We assessed resource use and costs for 12 months following diagnosis for
      women with abnormal Pap smears in Germany based on a sample of 138 women who had
      received abnormal results on Pap smears taken during March and April of 2004.
      Most women had a Pap IIID (57%) vs Pap III (20%) or Pap IV (23%). Women with a
      Pap IV consulted their gynaecologist more frequently than those with a Pap III or
      Pap IIID (5.6 visits vs 4.2 and 4.6 visits, respectively). Only 9% of patients
      underwent colposcopy plus biopsy; this may be due to the lack of histological
      assessment by coloposcopy and biopsy done currently in Germany. More women in the
      Pap IV group had a cold knife conisation, compared with those in the Pap IIID
      group, (84% vs 27%) hysterectomy (22% vs 4%) and laser coagulation (12.5% vs 4%).
      Median treatment duration was shorter for women with a Pap III than for those
      with Pap IIID and IV (3 vs 5 months, respectively). Overall, 28.3% of the women
      were hospitalised (median 5; range 1-33 days). The estimated average annual cost
      per patient was Euro 1,055, Euro 943 and Euro 3,174 for Pap III, IIID and IV,
      respectively. The cost of managing precancerous cervical lesions in Germany was
      shown to be high.

PMID- 18714568
TI  - Immunoexpression of HER family, neuregulin, MAPK and AKT in invasive ductal
      carcinomas of the breast.
AB  - BACKGROUND: The purpose of this study was to investigate the frequency of
      expression of the erbB/HER family of growth factor receptors, their ligand
      neuregulinalpha (NRGalpha) and the most important pathways activated by HER
      receptors that are mitogen-activated protein kinase (MAPK) and serine/threonine
      kinase (AKT) in invasive ductal carcinomas of the breast, not otherwise specified
      (IDC-NOS). METHODS: 59 of the IDC-NOS of the breast were studied for ER, PR,
      EGFR, c-erbB-2, c-erbB-3, c-erbB-4, neuregulin Ab-3, phospho-AKT, and phospho
      p44/42 map kinase using the streptavidin-biotin horseradish method. RESULTS: Of
      the 59 tumours, 44 (75%) were ER+, 37 (63%) PR+, four (7%) EGFR+, seven (12%) c
      erbB-2+, seven (12%) c-erbB-3+ and 14 (24%) c-erbB-4+alpha. Strong cytoplasmic
      and/or nuclear immunoexpression was revealed in 17 (29%) cases for NRGalpha, 13
      (22%) cases for p-AKT, and nuclear immunoexpression with p-MAPK was found in 17
      (29%) cases. CONCLUSION: The results suggest that high-grade breast carcinomas
      are not only associated with ER/PR- negativity, but seem to be activated by
      receptor tyrosine kinase growth factors.

PMID- 18714569
TI  - Differential gene expression analysis of ovarian cancer in a population isolate.
AB  - Gene expression products represent candidate biomarkers with the potential for
      early screening and therapy of patients with ovarian serous carcinoma. The
      present study, using patients that originate from the population isolate of South
      Tyrol, Italy, substantiates the feasibility of differential gene expression
      analysis in a genetically isolated population for the identification of potential
      markers of ovarian cancer. Gene expression profiles of fresh-frozen ovarian
      serous papillary carcinoma samples were analyzed and compared to normal ovarian
      control tissues using oligonucleotide microarrays complementary to 14,500 human
      genes. Supervised analysis of gene expression profiling data identified 225 genes
      that are down-regulated and 635 that are up-regulated in malignant compared to
      normal ovarian tissues. Class-prediction analysis identified 40 differentially
      expressed genes for further investigation as potential classifiers for ovarian
      cancer, including 20 novel candidates. Our findings provide a glimpse into the
      potential of population isolate genomics in oncological research.

PMID- 18714570
TI  - Study of p53 codon 72 polymorphism in patients with breast cancer.
AB  - Breast cancer is a common disease in Western societies, with an incidence of
      46.31/100,000 women/year in Brazil. The tumor suppressor gene TP53 is one of the
      most studied genes regarding the presence of mutations. Indeed, 50% of all tumors
      are known to exhibit changes in the TP53 nucleotide sequence due to carcinogenic
      processes. As to the presence of polymorphism, the TP53 gene is polymorphic at
      the nucleotide residue 347 (codon 72). In the current study, we examine if this
      polymorphism is associated with the clinicopathological parameters of breast
      cancer patients in a Brazilian population. One hundred and thirteen patients with
      breast cancer were included. The polymorphic region of the TP53 gene was PCR
      amplified from genomic DNA obtained from buccal cells. Specific primers for the
      Pro and Arg allele were used. Correlations of polymorphism with age, staging,
      nuclear grade, lymph node status, estrogen receptor status and lymphatic and/or
      blood vessel invasion were evaluated. Statistical analysis was performed using
      the Fisher's exact test. The frequency of p53 Arg/Arg was 57% and of the
      heterozygous allele Arg/Pro it was 39%. There was no correlation between
      polymorphism and clinicopathological parameters. According to our results, the
      TP53 polymorphism, at the 347 residue, is not associated with any
      clinicopathological findings of patients with breast cancer.

PMID- 18714571
TI  - Paget's disease of the vulva. A ten-year experience.
AB  - BACKGROUND: Paget's disease of the vulva is a rare neoplasmatic lesion which
      mainly affects postmenopausal women. METHOD:  RESULTS: We conducted a
      retrospective study during the period January 1996 till December 2005 in which 11
      cases of Paget's disease were detected. The clinical manifestations, management,
      specific pathological features, treatment and prognosis of each patient are
      presented. CONCLUSION: Surgical treatment is the current standard and long-term
      follow-up is required.

PMID- 18714572
TI  - Does vaginal intraepithelial neoplasia have the same evolution as cervical
      intraepithelial neoplasia?
AB  - BACKGROUND: Vaginal intraepithelial neoplasia is a little known disease which
      could be related to risk factors different from simple HPV infections. OBJECTIVE:
      To ascertain wheter vaginal lesions have a natural history similar to cervical
      lesions. MATERIALS & METHODS: A retrospective study to identify patients with
      vaginal lesions and synchronous cervical lesions through biopsy. The rate of mild
      cervical lesions (koilocytosis, warts, CIN I with and without koilocytosis) was
      compared with the rate of severe cervical lesions (CIN II and III, cervical
      carcinoma) in patients with mild vaginal lesions (warts and koilocytosis, and low
      grade VAIN) and in patients with severe vaginal lesions (high-grade VAIN). Using
      koilocytosis as a marker, the rate of "active" cervical lesions was compared with
      the rate of "non active" cervical lesions in patients with "active" versus "non
      active" vaginal lesions. Finally, the rates of mild and severe cervical lesions
      were compared among each group of VAIN (low-grade, high-grade, with or without
      koilocytosis). RESULTS: In patients with mild vaginal lesions, mild cervical
      lesions were significantly more frequent than severe cervical lesions. In
      patients with "active" vaginal lesions the rate of "active" cervical lesions was
      significantly higher than "non active" cervical lesions. The differences in rates
      of mild cervical lesions and severe cervical lesions among patients with high
      grade VAIN and low-grade VAIN (with and without koilocytosis) were not
      significant. CONCLUSION: These data suggest that CIN and VAIN may have some
      common features in certain cases, i.e., if an HPV infection is proved.

PMID- 18714573
TI  - Past obstetric history and risk of malignant breast neoplasms.
AB  - Many studies indicate hormonal disorders as a crucial reason for breast
      pathology. They are also probably responsible for the development of benign
      neoplasms and play a role in the origin and development of breast carcinoma.
      Although the mammary gland is under the influence of many steroid and peptide
      hormones such as thyroid hormones, prolactin, growth hormone,
      glucocorticosteroids, it is estrogen that plays an important role in the
      development of breast cancer. The purpose of the study was to analyze the
      obstetrical past of patients and the potential influence on the risk of
      developing malignant breast neoplasms. The participants in the study were healthy
      women with no changes in mammary glands (control group) and women with diagnosed
      malignant or benign breast neoplasms (study group). The total number of
      participants was 555 females aged 35-70 years. The study was carried out in the
      Greater Poland and Lubuskie province between 2005 and 2006. Hormonal disorders in
      childhood and puberty symptoms of early menarche play a crucial role in
      increasing the risk of malignant breast neoplasms. In women who experienced one
      or more miscarriages the risk of malignant breast neoplasms is significantly
      increased. On the basis of our study we calculated the odds ratio (OR) of
      malignant breast neoplasms among women who during lactation experienced problems
      needing medical intervention (OR = 2.25; 95% CI, 1.20-4.19) in comparison to
      women who experienced no problems).

PMID- 18714574
TI  - Prognostic significance of high-risk HPV persistence after laser CO2 conization
      for high-grade CIN: a prospective clinical study.
AB  - PURPOSE OF INVESTIGATION: To estimate the persistence rate of high-risk HPV DNA
      (HR-HPV DNA) in a population treated totally by laser CO2 conization for high
      grade cervical intraepithelial neoplasia (HG-CIN), and to examine if this
      persistence might be considered an independent risk factor for relapsing disease.
      METHODS: All women with a histological diagnosis of HG-CIN and planned for laser
      CO2 conization from January 2003 to December 2004 were prospectively submitted to
      a HR-HPV test prior to surgery and at three and six months of follow-up. Women
      providing written informed consent with 24 months of follow-up were enrolled in
      the study group. A positive HPV test, involvement of resection margins, age at
      first intercourse, smoking habits, parity and age at conization > 50 years old
      were considered as risk factors for relapsing HG-CIN during follow-up, and were
      univariately and multivariately analyzed to discover any independent influencing
      factors. RESULTS: Of HG-CIN 15.4% resulted not to be HPV related nor relapsing.
      The HPV clearance rate after treatment was 78.8%. Involvement of resection
      margins and HR-HPV DNA persistence post-treatment resulted as the only two
      statistically significant risk factors for HG-CIN recurrence (rate 3.8%). HR-HPV
      DNA persistence in follow-up resulted to be independent from other risk factors
      at multivariate analysis. CONCLUSIONS: Although able to reach a low recurrence
      rate of HG-CIN, laser CO2 conization does not remove HPV infection completely
      from the cervix with a case of persistence in every five treated patients. In our
      experience this persistence in itself represents an independent risk factor for
      developing relapsing disease and constitutes the basis to introduce HPV testing
      even in the follow-up of patients treated for HG-CIN by laser CO2 conization.

PMID- 18714575
TI  - A retrospective analysis of borderline ovarian tumors in a Greek university
      hospital.
AB  - PURPOSE: The aim of this retrospective study was to analyze the pathologic and
      clinical characteristics of borderline ovarian tumors. METHODS/RESULTS: During
      the period from January 1993 up to December 2002 we found 93 cases of borderline
      ovarian tumors. The mean age of patients was 44.3 years (range 28.9-59.7 years);
      77.4%, 10.8% and 11.8% of patients had Stage I, II and III, respectively. The
      histological outcomes revealed 52.7% of serous and 41.9% of mucinous origin;
      44.1% underwent radical surgery, whereas 55.9% had unilateral salpingo
      oophorectomy or cystectomy. The mean follow-up was 84 +/- 22 months. The overall
      five-year survival was 97.4% and 98% for mucinous and serous tumors,
      respectively. The survival rate was 100%, 90% and 81.8% in Stages I, II and III,
      respectively. CONCLUSION: From our results it can be concluded that borderline
      ovarian tumors have a favorable prognosis even after conservative management.

PMID- 18714576
TI  - Effect of intraoperative irrigation with alteplase on adhesion formation
      associated with intraperitoneal chemotherapy (experimental study).
AB  - OBJECTIVE: To examine the efficacy of intraoperative irrigation with alteplase, a
      tissue plasminogen activator, for the prevention of adhesion formation associated
      with intraperitoneal chemotherapy. MATERIAL AND METHODS: Rats, in which serosal
      injury was induced in the right uterine horn and ipsilateral parietal peritoneum,
      were randomly divided into four groups. Group 1 (n = 10) had intraoperative
      intraperitoneal irrigation with alteplase following the standard operation. Group
      II (n = 10) had irrigation with normal saline, while the rats in Group III (n =
      10) and Group IV received no peritoneal irrigation. All rats, except for those in
      Group IV, received intraperitoneal (IP) paclitaxel plus carboplatin chemotherapy
      on the seventh postoperative day, and all rats were sacrificed seven days after
      chemotherapy. Total adhesion scores in the induced standard defects were
      calculated by evaluating percentage of adhesion formation, as well as the
      severity and degree of the adhesions. The scores were compared among the groups.
      RESULTS: Comparison of the severity, percentage, degree and total score of
      adhesions among the groups demonstrated that subjects in Group I, where
      intraoperative alteplase irrigation was used, had fewer adhesion components
      (severity, percentage, degree) and a lower total adhesion score when compared to
      the other groups (p < 0.05). Adhesion components and the total adhesion score in
      Group IV, which did not receive chemotherapy, were found to be significantly
      lower when compared to Groups II and III (p < 0.05). CONCLUSION: Intraoperative
      Alteplase irrigation may reduce adhesion formation associated with
      intraperitoneal chemotherapy. Thus, intraperitoneal chemotherapeutic agents may
      be ensured to reach all peritoneal surfaces easily.

PMID- 18714577
TI  - Two rare cases of methotrexate-induced pneumonitis and pleurisy in patients with
      gestational trophoblastic neoplasms.
AB  - BACKGROUND: Pneumonitis is a serious and unpredictable side-effect of treatment
      with methotrexate (MTX) that may result in a life-threatening outcome. Pulmonary
      toxicity of methotrexate in patients with a gestational trophoblastic neoplasm
      (GTN) has rarely been reported before. CASE REPORTS: For the first time two cases
      of methotrexate-induced pneumonitis and pleurisy in GTN patients of Chinese
      ethnicity are presented. Two patients were both categorized as the low-risk
      group, and underwent a single regimen therapy of methotrexate. Their symptoms,
      such as fever, chest pain, acute nonproductive cough, dyspnea and hypoxemia did
      not respond to antibiotics immediately. Treatment with corticosteroids may be
      helpful. CONCLUSION: Awareness of pneumonitis and pleurisy, potentially life
      threatening complications of MTX, is very necessary and important to early
      recognition and treatment.

PMID- 18714578
TI  - Ovarian endometriosis associated with carcinoma and sarcoma: case report.
AB  - Endometriosis is a common clinical disorder that shares certain characteristics,
      metastasis and recurrence, with malignant neoplasms. Most malignant ovarian
      tumors arising from endometriosis are clear cell carcinoma or endometrioid
      adenocarcinoma. Few reports exist of sarcoma associated with endometriosis, and
      even fewer exist of multiple types of malignancies occurring simultaneously.
      Here, we report the case of a 32-year-old woman who presented with infertility
      and a pelvic mass. She underwent exploratory laparotomy and bilateral salpingo
      oophorectomy. She was then referred to our institution for treatment
      recommendation. The pathologic findings revealed bilateral endometrioid
      adenofibroma of low malignant potential, which was associated with endometrioid
      intraepithelial carcinoma in the left ovary and high-grade sarcoma in the right
      ovary. Both tumors seemed to have arisen from endometriosis. She was treated with
      75 mg/m2 of doxorubicin and 10 g/m2 of ifosfamide every three weeks for eight
      courses. She was later found to have bilateral brain metastases, which were
      resected and treated by whole-brain irradiation. She was again treated with
      doxorubicin and ifosfamide. The optimal treatment for endometriosis-associated
      ovarian cancer depends on the type of malignancy; simultaneously occurring
      multiple tumor types should be treated individually.

PMID- 18714579
TI  - A rare case of low-grade endometrial stromal sarcoma with myxoid differentiation
      and atypical bizarre cells.
AB  - Endometrial stromal sarcoma (ESS) is a rare mesenchymal tumor with characteristic
      histological appearances, consisting of diffuse infiltrate of small uniform
      endometrial stromal cells with a multinodular arrangement and distinct vascular
      pattern. Less common variants of ESS include "mixed endometrial stromal and
      smooth muscle tumors", "endometrial stromal tumors resembling ovarian sex cord
      tumors" and "endometrial stromal neoplasms with endometrial glands", and
      "aggressive endometriosis". Rarely do endometrial stromal tumors have a prominent
      fibrous or myxoid appearance which causes confusion and possible misdiagnosis as
      myxoid leiomyosarcoma. In this report we present a very unusual subtype of ESS in
      a 32-year-old woman. The tumor revealed atypical pleomorphic bizarre cells which
      were stained positive only with vimentin and CD10 in an abundant myxoid matrix. A
      low-proliferative rate was established with MIB-1 staining. To our knowledge such
      appearance has not been previously reported.

PMID- 18714580
TI  - Invasive squamous carcinoma of the vulva in women aged less than 40 years: report
      of two cases and a third case diagnosed during pregnancy.
AB  - PURPOSE OF INVESTIGATION: Invasive squamous cell cancer of the vulva (ISCC) is a
      rare disease in young patients and in pregnant women. The purpose of this paper
      was to investigate this type of cancer in women less than 40 years old and to
      present three cases, one which was diagnosed in the third trimester of pregnancy.
      METHODS: Three cases of invasive squamous cell cancer in women under age 40 among
      the retrospectively analyzed 52 vulvar cancer cases diagnosed between 1995-2002
      were investigated. RESULTS: Women aged 25, 39 and 31, respectively, had Stage 1,
      2 and 3 ISCC of the vulva. The first two cases had been spared by surgery and
      radiotherapy. The third patient was diagnosed during the last trimester of
      pregnancy. Although she was treated by radical surgery and postoperative
      radiotherapy, she had a recurrence in the inguinal region at 36 months, and died
      of disease 12 months later. CONCLUSION: Vulvar ISCC in young women may occur in
      association with or without predisposing factors. Although HPV-related type is
      predominant in the literature, keratinizing type of carcinoma may also be seen in
      this group of patients. Biopsy from suspected lesions is of paramount importance.

PMID- 18714581
TI  - Meningeal carcinomatosis as a late complication of brain metastases of epithelial
      ovarian carcinoma.
AB  - The brain represents a rare site of metastasis in patients with epithelial
      ovarian carcinoma (EOC). In recent decades there has been an apparent increase in
      the number of EOC patients diagnosed with brain metastases, probably as a result
      of improved prognosis of patients with advanced tumors, but cases of meningeal
      carcinomatosis complicating EOC remain rare. A patient with Stage III EOC had
      brain metastases diagnosed 31 months after primary surgery. The isolated brain
      metastases were controlled with radiosurgery, surgery and chemotherapy. Forty
      five months after the diagnosis of brain metastases, meningeal carcinomatosis was
      diagnosed which led, despite intrathecal therapy, to a fatal outcome. At autopsy,
      the disease was limited to the central nervous system. Meningeal carcinomatosis
      may represent a late fatal complication of brain metastases of EOC.

PMID- 18714582
TI  - Cervical cancer coexisting with small lymphocytic lymphoma detected during
      positron emission tomography/computed tomography simulation: a case report.
AB  - BACKGROUND: Positron emission tomography (PET)/computed tomography (CT)
      simulation in cervical cancer may help radiation oncologists to better define the
      target volumes. It may also detect extrapelvic lesions and incidental second
      malignancies, leading to significant changes in treatment management. CASE: A 63
      year-old woman who was deemed inoperable due to carcinoma of the cervical stump
      extending to the parametria and paraaortic lymph nodes detected on MR images
      presented for extended field radiotherapy. PET/CT simulation revealed an FDG avid
      mass in the cervical stump, and an enlarged axillary lymphadenopathy showing
      moderate FDG uptake. The excisional biopsy was consistent with small lymphocytic
      lymphoma (SLL). CONCLUSION: In our case, PET/CT simulation not only led to
      changes in treatment management, but also revealed a very rare coexistence of SLL
      and invasive squamous cell carcinoma of the cervix.

PMID- 18714583
TI  - In vitro fertilization in a patient with ovarian cancer (stage IC) following
      conservative surgery and chemotherapy: a case report.
AB  - A 30-year-old female underwent left salpingo-oophorectomy followed by
      chemotherapy for Stage IC adenocarcinoma of the ovary. Three years later she had
      ovarian hyperstimulation and in vitro fertilization (OH-IVF) resulting in a
      singleton pregnancy. During cesarean section peritoneal washings and biopsies
      were negative for recurrence. Seven years after the initial diagnosis, the
      patient is still free of any disease. In conclusion, OH-IVF may be considered in
      young patients with early ovarian cancer treated with conservative surgery and
      chemotherapy.

PMID- 18714584
TI  - Primary double invasive cervical carcinoma, squamous cell carcinoma and
      adenocarcinoma--case report.
AB  - A case of 56-year old women with double primary invasive cervical carcinoma,
      squamous cell carcinoma and endometrioid adenocarcinoma is presented. The patient
      was subjected to radical abdominal hysterectomy with pelvic and paraaortic
      lymphadenectomy. Surgery was followed by radiotherapy. Since the treatment the
      patient has been doing well and is free of any signs of relapse of the disease.

PMID- 18714585
TI  - Bilateral struma ovarii: a case mimicking an ovarian neoplasm.
AB  - We present a case of bilateral struma ovarii which developed postoperatively and
      was histopathologically diagnosed after the patient was hospitalized for
      investigation and treatment of tumoral anexal bilateral formations. There was no
      evidence of clinical malignancy or metastases. Data from the literature, together
      with histopathologic, diagnostic and therapeutic aspects of the disease were
      checked again taking into account the scarcity of this lesion, especially
      bilaterally.

PMID- 18714586
TI  - [Academic guidelines for the creation of a medical school curricula in Mexico].
AB  - Medical training curricula is a constantly evolving field. The objective of the
      present study is to analyze the changes the field has undergone. Our sources of
      information include demographic and health surveys, surveys carried out with
      students and faculty members and medical school guidelines from prestigious
      teaching centers. We compared medical curricula offered in Mexico as well as
      international trends. We analyzed context requirements, current status and future
      trends in biological, sociomedical and clinical disciplines; research and
      teaching methods; adequate academic programs. We describe the state of affairs in
      medical teaching in Mexico and the challenges that academic programs are
      currently facing. We propose a curricula with horizontal and vertical planning
      according to skills and competences that focus on health problems to foster
      scientific reasoning. Teaching strategies that are student-focused and foster
      significant/long-lasting learning. We suggest the need to include early clinical
      activities, communication skills and training in technological resources.
      Finally, there is a need to define a teaching profile that is consistent with
      training programs, to include experts in technology and modern teaching methods
      in order to establish permanent monitoring mechanisms, and to offer incentives to
      academics and administrative personnel.

PMID- 18714587
TI  - [Factor VIII activity among young Mexican patients with acute myocardial
      infarction].
AB  - BACKGROUND: Atherothrombotic disease is the leading cause of death worldwide.
      Most casualties are due to acute myocardial infarction (AMI). Patients younger
      than 45 years account for 5-10% of AMI cases. These patients generally do not
      display typical atherothrombotic risk factors. METHODS: Our cross-sectional study
      included adult patients under 45; men and women with AMI were included. A control
      group of healthy individuals matched for age, sex, and blood group was included
      to determine the role of several atherothrombotic risk factors on AMI. One
      hundred and sixty patients were included, the control group was comprised by 77
      males (m) and 83 females (f) RESULTS: Our results indicate that 25% of patients
      (23 m and 18 f) had increased FVIII compared with 8.8% of control subjects. Mean
      FVIII activity for patients and controls was 134 mg/dl (95%CI=114) vs. 118 mg/dl
      (95%CI=128-140), respectively (p=0.001). Prevalence of elevated FVIII was higher
      than the one found for hypertension or diabetes mellitus. HDL cholesterol was
      higher among patients than controls. Quantitative variables associated with AMI
      were high FVIII activity, blood monocyte count and HDL cholesterol. CONCLUSIONS:
      Classical atherothrombotic risk factors do not fully explain AMI events in the
      young. High levels of FVIII activity is a moderate but common risk factor in
      young people suffering AMI.

PMID- 18714588
TI  - [Oxygen peripheral saturation using pulse oxymetry among healthy term newborns at
      Mexico's altitude (2240 m)].
AB  - BACKGROUND: Oxygen peripheral saturation (SpO2) is crucial for an adequate
      management of critically-ill newborns infants (NB). The objective of the present
      study was to determine SpO2 by pulse oxymetry among healthy term and preterm NBs
      at an altitude of 2240 m above sea level. METHODS: Observational, cross-sectional
      and comparative. 218 NBs were prospectively studied between January to April
      2004. Eighty nine were term and 128 were preterm. Alpha levels were set at
      p<0.05. RESULTS: The recorded lower value for SpO2 was 88%, and the maximum was
      99%. We observed a significant SpO2 difference among the term NB (93.5+/-2%) and
      preterm NBs (92.9+/-2%), p=0.01. CONCLUSIONS: SpO2 in Mexico City's altitude is
      on average lower when compared to that observed at sea level. In general with a
      minimum and maximum values found in our study the SpO2 needed to maintain a
      critically sick NB with supplementary O2, is suggested. Values should be kept at
      between 88% and 94% to avoid hypoxemia and hyperoxemia.

PMID- 18714589
TI  - [Association between wound size after open cholecystectomy with severity of
      iatrogenic biliary tract lesions].
AB  - BACKGROUND: Transoperative biliary tract injury during open or laparoscopic
      cholecystectomy is a catastrophic event associated with significant morbidity and
      mortality. Our objective was to determine if wound size during open
      cholecystectomy is associated with more complex biliary tract injuries. METHODS:
      Prospective cohort study performed between March 2006 and February 2007. Sixty
      six patients with biliary tract injuries after open cholecystectomy were
      included. Wound size was analyzed. RESULTS: Sixty six patients were included, 70%
      were female with a median age of 44. Seventy four percent were treated for acute
      cholecystitis. Most participants were overweight or had various degrees of
      obesity. Biliary tract injuries were not recognized during the primary surgical
      procedure in 76% of cases. All patients with severe biliary tract injuries
      (Strasberg E-3 and E-4) had a wound size less than 10 cm in length. Wound size
      was associated with unrecognized injuries (p=0.000), as well as with injury
      severity (p=0.000). We were notable to demonstrate a statistically significant
      association between biliary tract injuries and elective or emergency surgical
      procedures and midline or subcostal surgical incision for cholecystectomy.
      CONCLUSIONS: Our findings suggest that minor surgical access during open
      cholecystectomy may constitute a risk factor since smaller incisions were
      associated with more severe biliary tract injuries and an inability to observe
      this damage during the surgical procedure. We suggest to adhere strictly to the
      guidelines of an adequate surgical exposure during open cholecystectomy to
      prevent biliary tract injuries.

PMID- 18714590
TI  - [Clinical and histopathological characteristics of malignant melanoma cases seen
      at "Dr. Manuel Gea Gonzalez" General Hospital].
AB  - BACKGROUND: Melanoma is a type of tumor that arises from melanocytes generally
      located in the dermoepidermal junction. Although melanoma is found in less than
      10% of cases, mortality is high representing 75% of deaths attributed to
      cutaneous cancer. There are four major subtypes: Superficial spreading melanoma,
      lentigo malignant melanoma, acral lentiginous melanoma and nodular melanoma.
      Superficial spreading melanoma is the most common type among Caucasians. In a
      Mexican case series, the nodular type is the most common type reported. The aim
      of this study was to determine the most common type seen at our medical facility.
      METHODS: We analyzed patient's medical records from March 1981 to December 2006.
      Demographic data included sex, age, place of residence, occupation, tumor
      progression, location and clinical description. Histologically we evaluated tumor
      thickness using the Breslow scale; invasion was measured using the Clark scale.
      This is a descriptive, cross-sectional and retrospective study. RESULTS: 165
      patients were studied, 112 were females and 53 males. The most common location
      was the lower limb. Acral lentiginous melanoma was the most common subtype.
      CONCLUSIONS: Our findings differ from the other series where they report nodular
      and superficial spreading melanoma as the most common types. The most common
      subtypes in our study were acral lentiginous melanoma and lentigo malignant
      melanoma among females, with a ratio of female-male of 2.1:1.

PMID- 18714591
TI  - [Social costs of the most common inflammatory rheumatic diseases in Mexico from
      the patient's perspective].
AB  - OBJECTIVE: To estimate the social costs of rheumatoid arthritis (RA), ankylosing
      spondylitis (AS), and gout from the patient's perspective. METHODS: We carried
      out a cross-sectional analysis of the cost and resource utilization of 690 RA,
      AS, and gout patients from 10 medical centers and private facilities in five
      cities of Mexico. The information was obtained from the baseline of a dynamic
      cohort. We estimated out-of-pocket expenses, institutional direct costs, and
      direct medical costs. RESULTS: The mean (SD) annual out-of-pocket expense (USD)
      was $610.0 ($302.2) for RA, $578.6 ($220.5) for AS, and $245.3 ($124.0) for gout.
      Figures correspond to 15%, 9.6%, and 2.5% of the family income. They also
      represented 26.1%, 25.3%, and 24.4% of the total annual cost per RA, AS, and gout
      patients, respectively. The expected direct institutional patient/year costs were
      1,724.2 for RA, $1,710.8 for AS, and $760.7 for gout. The total patient annual
      costs were $2,334.3 for RA, $2,289.4 for AS, and $1,006.1 for gout. Most out-of
      pocket expenses were used to purchase drugs, pay for laboratory tests, imaging
      studies, and alternative therapies. CONCLUSIONS: From the patient's perspective,
      the cost of RA, AS, and gout represents 25% of direct medical costs. The cost of
      RA is higher than that for AS and gout.

PMID- 18714593
TI  - [Is the risk of death real among home accidents?].
AB  - Descriptive study on damage to children's health caused by accidents. The
      literature has mainly focused on the analysis of severe trauma. The main
      objective was to assess the morbidity and mortality based on the authors
      experience and to propose special measures to prevent this type of trauma. Home
      accidents are a frequent form of pediatric trauma, yet reports in the literature
      are not always consistent with its real prevalence. We believe that home
      traumatic events have been underestimated and neglected mainly because they are
      generally not a cause of death, especially among infants. We analyzed 21 patients
      who underwent a traumatic lesion at home.

PMID- 18714592
TI  - [Association of pulmonar tuberculosis with HLA system antigens in Northeastern
      Mexico].
AB  - BACKGROUND: Genetic susceptibility to pulmonary tuberculosis (PTb) has been
      associated with the HLA (Antigens of the Human Leukocytes) system of the MHC
      (Major Histocompatibility Complex), mainly with HLA-DR and-DQ antigens. Based on
      this assumption we carried out a case control study to determine the association
      of PTb with the HLA-DR and-DQ antigens among a sample of patients attending a
      medical unit belonging to the Mexican Social Security System (IMSS). METHODS: HLA
      system phenotypes from cases (n=50) and controls (n=417), were defined
      serologically using a complement dependent microlymphocytotoxic assay. B
      lymphocytes were obtained using immunobeads. The allele and haplotype frequencies
      were determined using the Arlequin version 3.01 computer software. Relative risk
      (RR) was calculated with the Epimax Table Calculator. RESULTS: The alelles HLA
      DR11(5), -DR16(2) and -DQ7(3) and haplotypes /DR11(5)-DQ7(3), /DR14(6)-DQS(1) and
      /DR16(2)-DQ7(3) had a higher frequency in cases than in controls (RR>1, p<0.05).
      The HLA-DR17(3) and DQ8(3) alelles and /DR17(3)-DQ2 and /DR4-DQ8(3) haplotypes
      had a higher frequency among controls than among cases (RR<1, p<.05).
      CONCLUSIONS: These results indicate an association between PTb with the HLA-DR
      and -DQ antigens in a Mexican sample. Our results are similar to those found in
      the international literature.

PMID- 18714594
TI  - [Mexican clinical experience in ocular anti-angiogenic therapy].
AB  - Retinal pathological angiogenesis is the leading cause of visual loss in a wide
      variety of ocular diseases. Some of the examples include: Age-related macular
      degeneration, diabetic retinopathy and retinopathy associated with prematurity.
      These last two entities are, in addition, public health problems in developing
      countries. Recent physiopathological studies, have demonstrated that growth
      factors play a key role on angiogenesis. Anti-angiogenic therapy came about as an
      attempt to inhibit the action of growth factors over the process of pathological
      angiogenesis in order to preserve vision. The objective of this review is to
      describe Mexico's experience using this therapeutic approach.

PMID- 18714595
TI  - [Frailty, an enigmatic and controversial concept in geriatrics. The biological
      perspective].
AB  - Frailty is a controversial, complex and enigmatic concept. Because the world's
      population is aging, it has been possible to assess the impact of frailty over
      patients themselves as well as on their relatives, community and mainly on their
      caregivers. Health care personnel must be able to identify and understand this
      entity and its components. In addition during the 80's frailty was understood as
      synonymous with disability, chronic illness, or extreme aging; this perspective
      must be modified. The literature on frailty has increased exponentially in the
      last years. However, there is still not a well defined and universally recognized
      description or definition. The purpose of this review was to understand frailty
      and its consequences based on the most recent advances in the field of aging.
      Frialty is a multifactorial phenomenon and for purposes of this review, only
      biological characteristics are discussed.

PMID- 18714596
TI  - [A 60-year old man with history of hepatitis C during the last 15 years, febrile
      syndrome and loss of weight in the last month].

PMID- 18714597
TI  - [Women members of the Mexican National Academy of Medicine. An analysis of their
      membership and place in the medical elite].
AB  - This article analyzes women's admission to Mexico's National Academy of Medicine
      (NAM) originally an all-male institution. We describe the demographic
      characteristics of female members of the NAM. By the year 2006, the NAM had 536
      academic members, 62 of them were women. Data gathered included date of entry to
      the NAM, members' age at time of admission, current age, whether they had
      children and the field and or area to which they were assigned. We also analyzed
      membership to the "National System of Researchers" (Sistema Nacional de
      Investigadores, SNI). Women admitted to the NAM were all competitive scholars who
      planned their career choices, sought and achieved positions of power yet gender
      issues still determined their professional careers.

PMID- 18714598
TI  - [Molecular diagnosis in Huntington's disease].
AB  - Huntington's disease (HD) is a neurological degenerative disorder, inherited by
      an autosomal dominant mode, and caused by a CAG triplet expansion coding for a
      poly-glutamine sequence in the huntingtin protein. HD affects 5-10 in 100,000
      individuals from Caucasian population. Clinically patients display motor,
      cognitive and psychological impairment, and death within 10-15 years. Concrete
      advances have been achieved in the knowledge of the mutational mechanism,
      alteration of the protein product and their neuropathological effects. A number
      of tests such as PCR with or without DNA modification, Southern blot and mixed
      methods are analyzed. We describe their characteristics and effectiveness for the
      molecular diagnosis of HD.

PMID- 18714599
TI  - [Current therapeutic advances in the treatment of non-Hodgkin lymphoma].
AB  - Lymphoma is a lymphoid cell cancer that originates in lymphoid tissues. Non
      Hodgkin (NHL) type represents 90% of cases. In Mexico, NHL constitutes the third
      most common cancer in males and the sixth among females. NHL treatment has
      achieved significant advances in the last decade and NHL is currently becoming a
      disease with a high probability of cure. Rituximab has become an alternative for
      the treatment of NHL. Rituximab is a monoclonal antibody that targets the CD20
      antigen expressed in the mature malignant B cells. It induces NHL B cells
      destruction by complement-mediated citotoxicity, apoptosis and sensitization to
      the toxic effect of chemotherapy. Rituximab has revolutionized treatment results
      by offering patients with aggressive NHL a higher possibility of cure and in the
      case of the intractable forms of NHL it increases the disease free period. The
      standard treatment for a patient with NHL is rituximab-CHOP (immunotherapy). In
      addition, rituximab has pharmacoeconomic advantages as shown in various cost
      utility and cost-effectiveness studies.

PMID- 18714600
TI  - Not your grandmother's Alzheimer's disease. New priorities for research and care.
AB  - Thus, in terms of having non-pharmacological care recognized to be as important
      as pharmacological interventions and biomedical research, we must begin to
      consider the longer term effects of those interventions. It no longer seems
      appropriate to simply report on care recipient comfort and mood, decreased use of
      psychotropic medications, weight, and satisfaction. Studying care recipients in
      nursing homes is no longer enough. To have our contributions to dementia care
      recognized, nurses now must shift our attention to larger, more global ideas. We
      need to focus on maintaining individuals with dementia in their homes or other
      appropriate settings. It is only through the use of preventive and anticipatory
      measures that emphasize cost containment will nurses continue to be leaders in
      the field of dementia. This is not your grandmother's Alzheimer's disease.

PMID- 18714601
TI  - Surviving the storms: Emergency preparedness in Texas nursing facilities and
      assisted living facilities.
AB  - This study assesses the preparedness of long-term care facilities in Texas
      responding to Hurricanes Katrina and Rita. A 41-item questionnaire was mailed to
      facilities; the response rate was 42%. Among responding facilities, 4513
      residents were evacuated, and 6% of respondents reported resident death.
      Financial losses were reported by 8% of nursing facilities and 45% of assisted
      living facilities due to transportation and staff overtime. Respondents indicated
      the need for improved disaster preparednesstraining, better coordination, and
      transportation. Changes in policy and practice will lead to better trained staff
      who will provide the care residents need for improved health outcomes during
      future public health disasters.

PMID- 18714602
TI  - Older home-care patients' preferred approaches to depression care: a pilot study.
AB  - The purpose of this pilot study was to explore the approaches to depression care
      preferred by older home-care patients and examine characteristics associated with
      those preferences. Twenty-eight long-term home-care patients, ages 62 to 95, were
      interviewed. Patients ranked their depression care preferences and provided
      rationale for their responses. Results indicated prayer was preferred by the
      highest percentage of patients (50%). Comparing patients with and without
      depression experience, prayer was preferred by the latter group. The results
      highlight the importance of addressing patient preferences during care planning
      to improve participation in geriatric depression care management.

PMID- 18714603
TI  - Person-centered caregiving instruction for geriatric nursing assistant students:
      development and evaluation.
AB  - This research describes the development and evaluation of a 2-hour program that
      taught geriatric nursing assistant students person-centered caregiving skills.
      The person centeredness of caregiving skills among students who completed the
      training, as well as those who did not, was evaluated by coding their videotaped
      interactions with a standardized long-term care resident. Residents reported more
      satisfaction with students who had completed the special training, although there
      was little difference between the actual behavior of students in the intervention
      and control conditions. Students' interpersonal cognitive complexity was
      associated with their ability to provide care in person-centered ways.

PMID- 18714604
TI  - Spousal bereavement assessment: a review of bereavement-specific measures.
AB  - The death of a spouse represents a common form of bereavement among adults and is
      associated with significant distress and adaptation. This 10-year review of the
      bereavement literature highlights 12 tools used to assess bereavement in
      spousally bereaved samples. Pertinent measurement foci and psychometric
      properties of each tool are presented. Applicability of each tool within the
      spousal bereavement process is discussed, and aspects of the spousal bereavement
      process not currently addressed or under-addressed provide direction for future
      tool development.

PMID- 18714606
TI  - Is continuing competency too complex to tackle?

PMID- 18714605
TI  - Strategies for translating the resident care plan into daily practice.
AB  - The Omnibus Budget Reconciliation Act of 1987 required nursing facilities to
      complete a standardized comprehensive assessment known as the Resident Assessment
      Instrument (RAI) and to formulate a plan of care from the RAI to guide nursing
      care. The purpose of this retrospective case study was to examine the issues
      around the translation of nursing facility resident care plans to documents that
      guide daily care. Data were obtained by auditing 96 resident care plans in 10
      nursing facilities in two states. Despite the importance of the resident plan of
      care, the audit revealed the provider approaches to resident problems varied
      appreciably in nursing facilities. The results of this study support the need for
      further research to assist in the development and implementation of strategies in
      nursing facilities that focus on standardized practices. Consistent systems can
      be promoted that translate the resident care plan into daily practice.

PMID- 18714607
TI  - Stop to smell the roses.
AB  - Too often in our busy lives, we forget to take time to refresh and reenergize.
      Two recent personal experiences brought a renewed awareness of the need each of
      us has to periodically step back from our "busyness" and recharge our own
      batteries.

PMID- 18714608
TI  - Acute pancreatitis.
AB  - This column discusses the pathophysiology, signs and symptoms, complications,
      treatments, and care of acute pancreatitis.

PMID- 18714609
TI  - Developing a career as a nurse educator.
AB  - This column discusses developing and managing a career as a nurse educator.

PMID- 18714610
TI  - Using human simulation in the oncology clinical practice setting.
AB  - Patients are referred to the tertiary care teaching institution with diverse and
      sometimes rare diagnoses requiring complex therapy. Assuring that nurses in the
      oncology setting are delivering quality nursing care requires educational support
      that integrates evidence-based teaching methods. Clinical simulation holds
      promise for novice and experienced nurses to see the "big picture" associated
      with acutely ill oncology patients. Simulation scenarios focusing on commonly
      experienced oncologic emergencies are described, and practical information for
      the development and implementation of a simulation program is provided.

PMID- 18714611
TI  - The experiences of inactive nurses returned to nursing after completing a
      refresher course.
AB  - BACKGROUND: There are varied solutions to the nursing shortage, and one is
      returning inactive nurses to nursing. METHOD: This qualitative study used face-to
      face interviews to examine the experiences of nine nurses who returned to nursing
      after completing a refresher course. RESULTS: Financial benefits, children
      getting older, and purpose in life were reasons for taking the refresher course.
      The course was located by word of mouth, through the State Board of Nursing, and
      online. Supports included family, friends, motivation, self-paced study, and
      mentors. Barriers were obtaining clinical experience and getting questions
      answered. Seven of nine jobs related to the course clinical. Orientation with
      preceptors was important in employment. The nurses intended to remain employed
      until retirement. conclusion: Keeping track of nurses who become inactive and
      intentionally planning for their return could be a solution to the nursing
      shortage in the next decade.

PMID- 18714612
TI  - Continued nursing education in university hospitals in southern Brazil.
AB  - PURPOSE: This study analyzed the continued nursing education process in three
      university hospitals in southern Brazil. Its theoretical reference was centered
      upon the problematization pedagogy of Freire and the levels of practice of
      Vazquez. METHODS: This was a qualitative case study, based on multiple holistic
      cases. The data were collected through document analysis, observation of
      scenarios, and semistructured interviews with 22 nursing employees. RESULTS: The
      thematic analysis evidenced the continued nursing education process, highlighting
      initiatives such as the creation of the Center for Nursing Education and
      Research, the Permanent Nursing Education Center, and the Continued Nursing
      Education Program. CONCLUSION: This study serves as an important tool for the
      transformation of the reality of health care subjects and institutions.

PMID- 18714613
TI  - Professional values: the case for RN-BSN completion education.
AB  - BACKGROUND: Differences exist in the perception and enactment of professional
      values among practicing registered nurses (RNs). Hall's Care, Cure, and Core
      model was used as a framework for this study. METHODS: This study compared
      perceptions of professional values of 198 RNs according to their level of nursing
      education and other potentially influencial factors. An online survey developed
      by the researchers tested perceived professional values. RESULTS: A significant
      difference was found in perceived professional values according to level of
      nursing education, position or title, and professional organization membership.
      The highest level of perceived professional values was found among RN-BSN
      students. CONCLUSION: RN-BSN education should be promoted and a supportive
      infrastructure provided for the continuation of professional values.

PMID- 18714614
TI  - Precordial and oesophageal stethoscopes.

PMID- 18714615
TI  - The acquisition of airway skills by new trainee anaesthetists.

PMID- 18714616
TI  - Heart rate and outcome in patients with cardiovascular disease undergoing major
      noncardiac surgery.
AB  - There is an increasing awareness that an elevated resting heart rate is
      associated with increased all-cause mortality in the general population and that
      this may be an independent coronary risk factor This review was undertaken to
      determine whether heart rate is predictive of increased mortality and major
      morbidity in noncardiac surgical patients and whether heart rate manipulation
      improves perioperative outcome. A search of Medline from 1966 until October 2007
      was conducted using the terms "heart rate", "surgery", "cardiac", "morbidity",
      "mortality" and "perioperative". The main findings were that an elevated
      perioperative heart rate, an absolute increase in heart rate and heart rate
      lability are independent predictors of both short- and long-term adverse outcomes
      in patients at cardiovascular risk undergoing major noncardiac surgery. Although
      prospective nonrandomised and retrospective data suggest heart rate control
      improves perioperative outcome, there is conflicting evidence from randomised
      trials that perioperative heart rate control improves outcome. This may be
      because drug-associated bradycardia influences mortality in the perioperative
      period. Further studies reporting the absolute heart rate, the absolute change of
      heart rate and the time period of the observations are needed to identify 'early
      warning systems', which may allow earlier triage and improved outcome. Enthusiasm
      for this approach must be tempered by the appreciation that a J-shaped
      relationship probably exists between heart rate and morbidity, particularly
      following bradycardic therapy. Therefore, any bradycardic manipulation of heart
      rate in the perioperative period must be accompanied by simultaneous attention to
      other physiological variables associated with increased morbidity and mortality.

PMID- 18714617
TI  - Chlorhexidine--pharmacology and clinical applications.
AB  - Chlorhexidine is a widely used skin antisepsis preparation and is an ingredient
      in toothpaste and mouthwash. It is an especially effective antiseptic when
      combined with alcohol. Its antimicrobial effects persist because it is binds
      strongly to proteins in the skin and mucosa, making it an effective antiseptic
      ingredient for handwashing, skin preparation for surgery and the placement of
      intravascular access. Catheters impregnated with chlorhexidine and antimicrobial
      agents can reduce the incidence of catheter-related bloodstream infections.
      Contact dermatitis related to chlorhexidine is not common in health care workers.
      The incidence of contact dermatitis to chlorhexidine in atopic patients is
      approximately 2.5 to 5.4%. Acute hypersensitivity reactions to chlorhexidine are
      often not recognised and therefore may be underreported. This review discusses
      the pharmacology, microbiology, clinical applications and adverse effects of
      chlorhexidine.

PMID- 18714618
TI  - Anaesthesia trainees' exposure to airway management in an Australian tertiary
      adult teaching hospital.
AB  - The purpose of this study was to estimate the exposure of trainees to airway
      management techniques in an Australian tertiary adult teaching hospital.
      Anaesthesia records for all patients over a 20-week period were reviewed and the
      following data were obtained: the presence of a trainee, the type of airway used,
      the grade of the laryngoscopic view and the use of non-standard laryngoscopy for
      intubation. Data was recorded contemporaneously and analysed retrospectively. The
      data was then extrapolated to give a yearly estimate of airway procedures per
      trainee. There were 28 full-time trainees in the department over the study
      period. The estimated mean number of standard intubations performed per trainee
      per year was 157.4, with 2.9% being grade 3 or 4 laryngoscopies. The estimated
      mean annual numbers for other airway techniques were: 1.2 fibreoptic intubations,
      0.5 mask-only anaesthetics and 3.7 endobronchial double-lumen tubes. Our results
      suggest that trainees' exposure to airway management techniques is not extensive.
      As there is no previous study to determine experience gained by trainees, we are
      unable to establish whether there has been a decrease in experience, however we
      believe this is likely. Although competency is difficult to assess, it may be
      that this data has implications for training, unsupervised practice and
      rostering. Experience in certain airway skills may need to be supplemented using
      techniques such as simulation.

PMID- 18714619
TI  - Airway experience of anaesthetic registrars.
AB  - Education and expertise in airway skills are central components of anaesthesia
      training, yet there is no formal monitoring of the airway experience or level of
      competence that registrars actually obtain. An audit was performed in two phases
      to prospectively document the airway management experience of registrars in one
      teaching hospital department. Novices were studied for three months and
      subsequently, the whole registrar group for one month. Novice registrars
      performed a mean of two facemask anaesthetics, 19 laryngeal mask airways and 20
      endotracheal intubations per month in their first three months of anaesthetic
      practice. The overall registrar group performed a mean of 18 laryngeal mask
      airways and 19 endotracheal intubations in the study month. Our findings indicate
      that the airway experience of anaesthesia trainees may be inadequate and
      therefore warrants further investigation.

PMID- 18714620
TI  - Continuous infusion of subcutaneous compared to intravenous insulin for tight
      glycaemic control in medical intensive care unit patients.
AB  - The aim of this randomised controlled study was to compare continuous
      subcutaneous insulin infusion using an insulin pump with the traditional
      continuous intravenous infusion method for tight glycaemic control. Sixty
      patients admitted to our University Hospital medical intensive care unit with an
      initial blood glucose level over 6.1 mmol/l, were enrolled and randomised into
      two treatment groups: the subcutaneous insulin group received continuous
      subcutaneous insulin infusion and the intravenous group received insulin by
      traditional intravenous infusion with infusers. Three patients died in the first
      24 hours and were excluded from the final analysis. Insulin therapy was
      administered to both groups according to the previously designed and used
      protocol in the department. The target glucose level was 4.4 to 6.1 mmol/l. There
      was no significant difference in mortality between the groups. However mean blood
      glucose level was found to be lower (6.56+/-0.82 mmol/l vs. 7.85+/-1.6 mmol/l,
      P=0.00055) in the subcutaneous insulin group. According to Vogelzang's
      hyperglycaemic index, better glycaemic control was achieved in the subcutaneous
      insulin group while there was no significant difference in terms of hypoglycaemic
      events. Daily insulin bolus and infusion requirements were also significantly
      lower in the subcutaneous insulin group. Despite the small number of patients
      involved in this study in a medical intensive care unit, strict blood glucose
      control using a subcutaneous insulin pump was achieved more efficiently than the
      traditional intravenous infusion method without increasing hypoglycaemic events.

PMID- 18714621
TI  - Sequential organ failure assessment score and comorbidity: valuable prognostic
      indicators in chronically critically ill patients.
AB  - Chronically critically ill patients are defined as those who survive initial life
      threatening, possibly reversible organ failure(s) but are unable to recover
      rapidly to a point at which they are fully independent of life support.
      Accordingly, these patients require mechanical ventilation and medical resources
      for a long time in an intensive care unit (ICU). The present study analysed
      demographic, clinical and survival data of chronically critically ill patients,
      to identify condition(s) related to poor prognosis. A total of 141 chronically
      critically ill patients were studied retrospectively over a two-year period (July
      1, 2003 to June 30, 2005). Their mean lengths of stay in the ICU and in the
      hospital were 42.9+/-36.4 and 83.9+/-100.5 days respectively. ICU and six-month
      cumulative mortality rates were 42.6% and 75.9% respectively. Non-survivors had a
      significantly higher Sequential Organ Failure Assessment (SOFA) score than
      survivors on day 21 of ICU admission, as well as having significantly lower
      changes of SOFA scores between days three and 21. Multivariate analysis
      demonstrated that the SOFA score on day 21 and the Charlson Comorbidity Index
      were the best predictor of survival for six months after hospital discharge. The
      SOFA score on day 21 and comorbidity in the ICU appears to be a valuable
      prognostic indicators in chronically critically ill patients.

PMID- 18714622
TI  - Alpha1-adrenergic receptor mRNA and inflammatory mediator expression in
      circulating leucocytes after cardiac surgery.
AB  - Vasodilation after coronary artery bypass surgery is a common complication.
      Inflammatory mediators influence the expression of alpha1-adrenergic receptors.
      Do patients requiring high doses of postoperative inotropic support have down
      regulated alpha-adrenergic receptors? Is there a characteristic pattern of
      preoperative inflammatory mediator expression that could predict a complicated
      course after the operation? Forty-four patients undergoing cardiac bypass surgery
      with extracorporeal circulation were prospectively investigated. Five
      perioperative blood samples were taken (preoperative, two hours, 12 hours, 36
      hours and 72 hours postoperative). The leucocyte mRNA-expression of the three
      alpha1-adrenergic receptor subtypes (A, B and D) and 11 different pro
      inflammatory mediators were investigated with the real-time reverse transcriptase
      polymerase chain reaction. The patients were divided into three groups (No
      noradrenaline [No-NA]= 0 microg/min, Low-noradrenaline [Low-NA]=0.1-7 microg/min,
      High-noradrenaline [High-NA] >7 microg/min), according to their postoperative
      noradrenaline requirements. Preoperatively, alpha1(A)-receptor expression was 4.9
      fold (High-NA) and 18.7-fold (Low-NA) higher than the No-NA group (P=0.005) and
      plasma noradrenaline levels were higher in the High-NA group (P=0.005). Across
      all groups at 12 hours after the operation, alpha1(A) -receptor expression
      decreased to approximately one-fifth of preoperative levels (P=0.01); but with
      greater duration and magnitude of relative decrease in the High-NA group.
      Patients in the No-NA group had significant postoperative increases in leucocyte
      inflammatory mediator expression for IL-1beta, TLR4, TREM, MPO, MMP9 and TNF
      genes, whereas the changes in the Low-NA and High-NA groups were not significant.
      Low preoperative levels of noradrenaline and low expression of alpha1(A)
      adrenoreceptors in leucocytes was associated with less probability of requiring
      noradrenaline support after cardiac surgery.

PMID- 18714623
TI  - The effect of timing of application of positive end-expiratory pressure on
      oxygenation during one-lung ventilation.
AB  - Many studies have confirmed that applying positive end-expiratory pressure (PEEP)
      to the dependent lung during one-lung ventilation (OLV) improves oxygenation. Our
      purpose was to investigate the best time and level of PEEP application. Thirty
      patients undergoing thoracic surgery were randomised into three groups. After 20
      minutes of two-lung ventilation (TLV) in the lateral position, all patients
      received OLV for one hour During OLV, 0, 5, 10 cmH2O PEEP were applied in order
      in group A, with each level sustained for 20 minutes. Group B had 5 cmH2O PEEP
      applied and maintained for one hour Patients in group C received PEEP with levels
      set in the opposite order to that of group A. The ventilation model was then
      converted to TLV. PaO2, PaCO2 and respiratory mechanical variables were compared
      at five different time points among groups, 20 minutes after TLV (T1), 20 (T2),
      40 (T3) and 60 minutes (T4) after OLV and 20 minutes after conversion to TLV
      (T5). We found that PaO2 was lower in group A than the other two groups at T2 (P
      <0.05). PaO2 decreased significantly at T5 compared with T1 (P <0.05) in group A
      only. When PEEP was set to 10 cmH2O, the airway pressure increased significantly
      (P <0.05). These findings indicate that PEEP applied at the initial time of OLV
      improves oxygenation most beneficially. Five cmH2O PEEP may produce this
      beneficial effect without the increase in airway pressure associated with 10
      cmH2O PEEP.

PMID- 18714624
TI  - The performance of Drager Oxylog ventilators at simulated altitude.
AB  - Ventilated patients frequently require transport by air in a hypobaric
      environment. Previous studies have demonstrated significant changes in the
      performance of ventilators with changes in cabin pressure (altitude) but no
      studies have been published on the function of modem ventilators at altitude.
      This experiment set out to evaluate ventilatory parameters (tidal volume and
      respiratory rate) of three commonly used transport ventilators (the Drager Oxylog
      1000, 2000 and 3000) in a simulated hypobaric environment. Ventilators were
      assessed using either air-mix (60% oxygen) or 100% oxygen and tested against
      models simulating a normal lung, a low compliance (Acute Respiratory Distress
      Syndrome) lung and a high-resistance (asthma) lung. Ventilators were tested at a
      range of simulated altitudes between sea level and 3048 m. Over this range, tidal
      volume delivered by the Oxylog 1000 increased by 68% and respiratory rate
      decreased by 28%. Tidal volume delivered by the Oxylog 2000 ventilator increased
      by 29% over the same range of altitudes but there was no significant change in
      respiratory rate. Tidal volume and respiratory rate remained constant with the
      Oxylog 3000 over the same range of altitudes. Changes were consistent with each
      ventilator regardless of oxygen content or lung model. It is important that
      clinicians involved in critical care transport in a hypobaric environment are
      aware that individual ventilators perform differently at altitude and that they
      are aware of the characteristics of the particular ventilator that they are
      using.

PMID- 18714625
TI  - Relative reliability of the auditory evoked potential and Bispectral Index for
      monitoring sedation level in surgical intensive care patients.
AB  - Sedation is an important adjunct therapy for patients in the intensive care unit.
      The objective of the present study was to observe correlation between an
      established subjective measure, the Ramsay Sedation Scale, and two objective
      tools for monitoring critically ill patients: the Bispectral Index (BIS) and
      auditory evoked potential. Ninety patients undergoing major surgery scheduled for
      postoperative mechanical ventilation and continuous sedation with propofol and
      fentanyl were selected. Electrodes for determining BIS and auditory evoked
      potential were placed on the foreheads of all patients according to
      manufacturer's specifications at least six hours after patients' arrival at the
      intensive care unit. Ramsay Sedation Scale, BIS, signal quality index, composite
      A-line autoregressive index (AAI) and electromyographic activities were recorded
      every five minutes for 30 minutes. BIS and AAI showed good correlation amongst
      readings (r(s)=0.697, P <0.01). Both were significantly influenced by
      electromyographic activities (BIS, r(s)=0.735, P <0.01; AAI, r(s)=0.856, P
      <0.01). Comparison of BIS and AAI revealed an acceptable correlation between
      electroencephalogram variables and the Ramsay Sedation Scale (BIS, tau=-0.689;
      AAI, tau=-0.621; P <0.01). In conclusion, the auditory evoked potential and BIS
      monitors revealed an acceptable correlation with the Ramsay Sedation Scale.
      However, the BIS and auditory evoked potential monitors do not perform adequately
      as a substitute in the assessment of sedated intensive care unit patients. These
      monitors could be used as part of an integrated approach for the evaluation of
      those patients especially when the subjective scales do not work well in the
      setting of neuromuscular blockade or may not be sufficiently sensitive to
      evaluate very deep sedation.

PMID- 18714626
TI  - Predictors of outcome of ruptured aortic aneurysms in a metropolitan hospital.
AB  - The mortality in patients presenting with ruptured abdominal aortic aneurysm
      remains high. In this study we aimed to assess the outcome and factors predicting
      the mortality in patients admitted to a teaching hospital with the diagnosis of
      ruptured abdominal aortic aneurysm. During the study period (July 2001 to July
      2007) all patients admitted with a diagnosis of a ruptured abdominal aortic
      aneurysm were included. There was a total of 62 patients with a mean age of 76
      years. The hospital mortality was 32.3% (20 patients). Twelve patients (19.4%)
      were discharged home, 25 patients (40.3%) were discharged to rehabilitation and
      five patients (8%) were discharged to other hospitals for further care. There was
      a significant difference between survivors and non-survivors in age, loss of
      consciousness at presentation and duration of hospital stay. Logistic regression
      analysis of these variables suggests the presence of chronic obstructive
      pulmonary disease (P=0.04, odds ratio 6.7, 95% confidence interval 1.1 to 41.3)
      and age (P=0.02, odds ratio 1.2, 95% confidence intervals 1.0 to 1.3) to be
      independently associated with mortality. These results compare favourably with
      published Australian as well as the international data.

PMID- 18714627
TI  - A comparison of screen-based simulation and conventional lectures for
      undergraduate teaching of crisis management.
AB  - In our institution, we introduced a screen-based simulator to our undergraduate
      lectures on medical crisis management. We hypothesised that this novel use of the
      screen-based simulator would be as effective as our conventional lectures. To
      test this we randomly divided medical students into two groups. Students in Group
      A were taught medical crisis management (heart failure and anaphylaxis) using a
      screen-based simulation program projected onto a shared screen, with a
      facilitator guiding the students through the scenarios. Simultaneously, students
      in Group B were lectured the same content without the screen-based simulation.
      Both groups were allotted exactly one hour Several days later, students were
      tested on their management of anaphylaxis using the Human Patient Simulator. A
      blinded marker assessed them on diagnosis, resuscitation, specific treatment,
      call for help and for reassessment of the patient. Students also answered a
      questionnaire on their experience. Sixty-four students participated in the study.
      Both groups had similar overall scores. However students in Group A scored better
      in the specific treatment category by a factor of 1.7. Students in both groups
      rated their learning experiences highly. This study showed that screen-based
      simulation was as effective as conventional lectures and might be even more
      effective in some areas.

PMID- 18714628
TI  - Sedation and delirium in the intensive care unit: an Australian and New Zealand
      perspective.
AB  - A survey was conducted to determine sedation and delirium practices in Australian
      and New Zealand intensive care units. The survey was in two parts, comprising an
      online survey of reported sedation and delirium management (unit survey) and a
      collection of de-identified data about each patient in a unit at a given time on
      a specified day (patient snapshot survey). All intensive care units throughout
      Australia and New Zealand were invited by email to participate in the survey.
      Twenty-three predominantly metropolitan, level III Australian and New Zealand
      intensive care units treating adult patients participated. Written sedation
      policies were in place in 48% of units, while an additional 44% of units reported
      having informal sedation policies. Seventy percent of units routinely used a
      sedation scale. In contrast, only 9% of units routinely used a delirium scale.
      Continuous intravenous infusion is the primary means of patient sedation (74% of
      units). While 30% of units reported routinely interrupting sedation, only 10% of
      sedated patients in the snapshot survey had had their sedation interrupted in the
      preceding 12 hours. Oversedation appears to be common (46% of patients with
      completed sedation scales). Use of neuromuscular blockade is low (10%) compared
      to other published studies. Midazolam and propofol were the most frequently used
      sedatives. The proportion of patients developing delirium was 21% of assessable
      patients. Failed and self-extubation rates were low: 3.2% and 0.5% respectively.
      In Australian and New Zealand intensive care units, routine use of sedation
      scales is common but not universal, while routine delirium assessment is rare.
      The use of a sedation protocol is valuable and should be encouraged.

PMID- 18714629
TI  - The use of extracorporeal carbon dioxide removal in the management of life
      threatening bronchospasm due to influenza infection.
AB  - We report the use of the Novalung interventional Lung Assist extracorporeal
      carbon dioxide removal device, (Novalung GmbH, Lotzenacker 3, D-72379 Hechingen,
      Germany) to treat a 46-year-old female with life-threatening bronchospasm
      secondary to influenza infection. Despite maximal treatment she developed severe
      hypercapnia and acidosis. The necessity for high inflation pressures led to the
      development of gross surgical emphysema. Use of the interventional Lung Assist
      enabled a rapid correction of hypercapnoea and acidosis, allowing a reduction in
      airway pressures, reducing further barotrauma. Subsequent resolution of the
      inflammatory process allowed removal of the interventional Lung Assist after 11
      days. She was successfully weaned from mechanical ventilation and made a full
      recovery.

PMID- 18714630
TI  - Acute airway obstruction secondary to achalasia mega-oesophagus.
AB  - Acute airway obstruction is a very rare presentation of achalasia. We report the
      case of a 78-year-old woman with previously undiagnosed achalasia who presented
      with acute respiratory distress and stridor due to tracheal compression by mega
      oesophagus. Anaesthetists and physicians caring for patients with achalasia must
      be aware of the need for emergency oesophageal decompression in this rare and
      life-threatening condition.

PMID- 18714631
TI  - Fatal vitamin C-associated acute renal failure.
AB  - Although daily ingestion of high-dose vitamin C is generally regarded as largely
      innocuous, fatal nephrotoxicity can occur in some rare circumstances. We report a
      case where the patient, who chose to forgo any advanced conventional medical
      intervention (dialysis and mechanical ventilation), had failed to disclose his
      use of high-dose vitamin C and subsequently died. Intra-renal oxalate crystal
      deposition was demonstrated at autopsy. Directed enquiry with the family then
      revealed his high-dose vitamin C usage. Even though fully-informed discussion was
      limited by incomplete prospective disclosure, it remains the prerogative of any
      competent patient to decline any treatment, including those that may be
      considered life-saving.

PMID- 18714632
TI  - "Conscious sedation".

PMID- 18714633
TI  - When pharmacology and psychology do not mix.

PMID- 18714634
TI  - Beware delayed upper airway obstruction after inadvertent carotid artery
      puncture.

PMID- 18714635
TI  - Preoperative atropine treatment and fever in children.

PMID- 18714636
TI  - Detachment of Vital Signs Non-latex Breathing Bags 3L during manual ventilation.

PMID- 18714637
TI  - Another benefit of ultrasound imaging in anaesthesia.

PMID- 18714638
TI  - Failure of transcutaneous pacing in a head-injured patient.

PMID- 18714639
TI  - Beware kinking of disposable plastic circuit tubing during anaesthesia.

PMID- 18714640
TI  - Strabismus incidence in infants born in Split-Dalmatia County 2002-2005.
AB  - The aim of the study was to determine the incidence of strabismus in preterm
      infants born between 2002 and 2005 in Split-Dalmatia County, and to compare it
      with term infants. Data were collected from Department of Public Health, Split
      Dalmatia County and Strabology Outpatient Department, University Department of
      Ophthalmology, Split University Hospital Center. Strabismus was present in 796
      (3.97%) children born between 2002 and 2005. Strabismus was diagnosed in 1.37% of
      term infants and 17.57% of preterm infants. Various factors can produce disorders
      in preterm infants, such as diffuse and focal defects of the white brain matter,
      and disorders of oligodendroglial cells, which may explain the higher incidence
      of strabismus in preterm infants as compared with term infants.

PMID- 18714641
TI  - An epidemic outbreak of Salmonella typhimurium in a Romany ethnic community--a
      clinical-epidemiological survey.
AB  - An epidemic outbreak in October 2005 in a Romany community associated with
      consumption of minced meat, produced and sold by a private manufacturer without
      any sanitary surveillance is reported. Salmonella typhimurium was confirmed as an
      etiologic agent. The aim was to study the clinical and epidemiological findings
      in this outbreak. The study group included 40 Romanies, 15 male and 25 female,
      aged 2 to 77 years. Clinical, laboratory, microbiological and epidemiological
      investigations were performed. Twenty two (55%) patients had clinical
      manifestations such as prostration, fever and diarrhea. A mild clinical form was
      observed in 6, moderate form in 9 and severe form in 7 patients. Eighteen (45%)
      patients were asymptomatic. Most patients had typical clinical presentation,
      whereby moderate and severe forms prevailed. Using foodstuffs beyond sanitary
      control is quite possible in a Romany community because of poor living conditions
      and low health education.

PMID- 18714642
TI  - Oral lesions in patients with pemphigus vulgaris and bullous pemphigoid.
AB  - Thirty three patients admitted to the University Department of Dermatology and
      Venereology, Sestre milosrdnice University Hospital, were included in the study.
      The purpose of the study was to compare data on age and gender, habits, lesion
      localization, onset of symptoms and therapy between patients with pemphigus
      vulgaris and those suffering from bullous pemphigoid. Based on clinical
      presentation, histopathologic analysis, direct and indirect immunofluorescence,
      Tzanck smear and desmogleins, 15 cases of pemphigus vulgaris and 18 cases of
      bullous pemphigoid were diagnosed. The results obtained indicated an increased
      prevalence of pemphigus vulgaris in middle-aged patients (46.6% of patients were
      aged between 50 and 70), while bullous pemphigoid predominantly affected elderly
      individuals (83.3% of patients were older than 70). Pemphigus vulgaris showed a
      female predominance (female 66.6% vs. male 33.4%), while no sex difference was
      recorded for bullous pemphigoid. Patients with both diseases presented with
      cutaneous and/or oral lesions. The majority of patients with pemphigus vulgaris
      had skin lesions with oral manifestations (86.6%), whereas in 40% of cases oral
      lesions were preceded by the cutaneous ones. Mucosal erosions were found in only
      16.6% of patients with bullous pemphigoid. The majority of patients were
      administered systemic and topical corticosteroid therapy with adjuvant systemic
      immunosuppressant therapy. Timely recognition of pemphigus vulgaris and bullous
      pemphigoid and appropriate treatment are important for the prognosis of these
      autoimmune bullous disorders.

PMID- 18714643
TI  - Myeloid sarcoma in the central nervous system: case report and review of the
      literature.
AB  - Myeloid sarcomas are rare manifestations of mainly myeloblastic leukemia. Their
      occurrence in the central nervous system is exceptional and current literature is
      limited to case studies. A case is added herewith and a review was performed to
      investigate clinical characteristics and treatment options of central nervous
      system myeloid sarcoma. A 61-year-old female with acute myeloblastic leukemia
      (FAB M5) and progressive left sided hemiparesis showed a right parieto-occipital
      epidural lesion mimicking meningioma. Partial resection was performed to reveal a
      myeloid sarcoma. Reviewing the literature we identified 44 cases with sufficient
      description of the diagnosis, treatment and follow up to one year. In these
      patients different treatment regimens were applied. However, when systemic
      chemotherapy or irradiation was included in the treatment regimen, patients
      showed the best 1-year survival proportion.

PMID- 18714644
TI  - Variations in clinical presentation of basal cell carcinoma.
AB  - Basal cell carcinoma (basalioma, BCC) is the most common skin cancer and the most
      common human malignancy in general, with a continuously increasing incidence. In
      most cases, BCC develops on chronically sun-exposed skin in elderly people, most
      commonly in the head and neck region. Besides chronic UV radiation, other risk
      factors for the development of BCC include sun bed use, family history of skin
      cancer, skin type 1 and 2, a tendency to freckle in childhood, immunosuppression,
      previous radiotherapy, and chronic exposure to certain toxic substances such as
      inorganic arsenic. There are numerous variations in clinical presentation of BCC,
      such as nodular BCC, ulcerating BCC, pigmented BCC, sclerosing BCC, superficial
      BCC, and fibroepithelioma of Pinkus. Each varies in terms of clinical
      presentation, histopathology and aggressive behavior. Treatment modalities for
      BCC include surgical excision, cryosurgery, curettage, electrodessication,
      radiotherapy, photodynamic therapy, topical cytostatics, and immunomodulators. If
      left untreated or inadequately treated, BCC may become invasive and locally
      destructive, although it very rarely metastasizes. Due to the extremely high
      incidence of BCC, medical professionals should be familiar with its manifold
      clinical presentations.

PMID- 18714645
TI  - [Prophylactic colectomy in hereditary colorectal cancer].
AB  - Hereditary colorectal cancer conditions are associated with a very-high life-time
      risk of colorectal cancer and require an intensive endoscopic surveillance
      programme. All colorectal lesions identified during follow-up should be
      endoscopically removed. Colectomy should be considered when these lesions are not
      amenable to endoscopic resection because of their morphological characteristics
      and/or their multiplicity. In fact, colectomy or coloproctectomy is indicated in
      virtually all patients with classical form of familial adenomatous polyposis as
      they develop hundreds of adenomatous polyps during their second decade of live.
      In any case, it is recommended that surgical decisions are discussed in
      multidisciplinary teams and that surgery is performed in highly specialized
      centres.

PMID- 18714646
TI  - [Recent advances in cataract surgery].
AB  - The objective recognition of the effects and the degradation of optical function
      caused by an early cataract are possible using non-invasive ocular optical
      sensing and scattering measurement. This may help the physician to decide when
      cataract surgery is appropriate. Cataract surgery has evolved into an ambulatory
      procedure that requires minimal anesthesia and significantly improves visual
      function by removing the opaque crystalline lens. Bimanual or co-axial
      microincisional phacoemulsification cataract surgery has recently become a
      procedure of interest among cataract surgeons, and a number of trials have shown
      its potential as a minimally invasive cataract surgery. In addition, patients may
      have a choice about the type of synthetic lens implant that fits their visual
      needs. The use of aspheric IOLs for lens replacement reduces spherical aberration
      and therefore improves the optical quality of the eye. Bilateral multifocal IOL
      implantation is effective and safe in selected cataract patients, providing very
      good uncorrected distance and near visual acuity. Slightly reduced contrast
      sensitivity and increased perception of glare/halo are seem to represent an
      acceptable compromise for near, as well as distance vision improvement

PMID- 18714647
TI  - [Thrombotic microangiopathies].

PMID- 18714648
TI  - [Loss of motivation in the elderly].
AB  - The loss of motivation is frequent in aged person and sometimes is difficult to
      assess. It is associated with depression but not exclusively. It overlaps with
      frontal brain aging consequences. Moreover, somatic problems can interfere with a
      loss of motivation; loss of motivation is frequent with exhausting chronic
      diseases, cognitive impairment and it facilitates the social withdrawal. In
      elderly, loss of motivation blunts the intensity of moral pain. Depressions with
      conative disorders can move in a dysexecutive syndrome. Even if, owing to the
      treatment, the cognitive disorders disappear, several years after, an authentic
      dementia can be diagnosed. With aging process, elderly must cope with losses,
      less or more balanced: affective, physical and financial losses, triggering the
      reject of any personal commitment. Aging process also concerns brain amines,
      especially dopamine, exposing old persons to depression. It alters by a similar
      way others brain neuro-mediator, such acetylcholine, involved in dementia. Both
      loss motivation and executive disorders have to be systematically assessed. An
      antidepressant therapeutic is necessary in case of doubt, improving patients
      thymic status, quality of life of patients and their family, and sometime of
      frontal dysfunctions.

PMID- 18714649
TI  - [Puberty. Addressing family questions and concerns].

PMID- 18714650
TI  - [Biological mechanisms and genes involved in puberty].
AB  - Puberty is an important step in human development. Onset of puberty, including
      neurobiological mechanisms important for the increase of hypothalamic GnRH pulses
      remains a mystery. After birth, GnRH secretion remains elevated and then
      decreases during childhood regardless of any steroid gonadal feedback. This
      period of quiescence of the gonadotropic axis during childhood is linked to a
      central inhibition of GnRH secretion which is replaced by an activator tone at
      puberty. The study of the pathology of the pubertal timing, including delayed
      puberty led to the discovery of new genes involved in the migration of GnRH
      neurons and genes involved in the neuroendocrine regulation of the gonadotropic
      axis. Recently, the emphasis on the importance of the kiss/GPR54 system in
      modulating control of the gonadotropic axis at puberty has recently emerged from
      Human genetics studies.

PMID- 18714651
TI  - [Normal puberty].
AB  - Puberty refers to a collection of somatic and psychic maturation phenomena,
      leading from juvenile to adult state. It is characterized by the development of
      secondary sex characteristics, growth spurt and changes in body composition and
      bone mineralization. It leads to the establishment of the reproductive function.
      The onset of puberty is influenced by environmental and neuroendocrine factors. A
      few diagnostic tests can prove useful to confirm the onset of puberty: bone age x
      rays, pelvic echography in girls, estradiol assay in girls and testosterone assay
      in boys.

PMID- 18714652
TI  - [Precocious pubertal].
AB  - Precocious pubertal is frequent and should lead to a rigorous evaluation. It is
      important to precisely evaluate the timing of pubertal development, and to search
      for an hypothalamic lesion in cases of central precocious puberty. It is also
      important to recognize that many cases of precocious puberty will not progress
      and therefore do not need treatment. When central precocious puberty has been
      confirmed, GnRH agonists should be considered. Management issues, as well as long
      term results of these treatments are presented.

PMID- 18714653
TI  - [Pubertal delay].
AB  - Puberty is the phenomenon that conducts to reproductive maturation. Delayed
      puberty is defined in girls by the absence of breast development beyond 13-years
      old or primary amenorrhea beyond 15-years-old, and in boys by the absence of
      testicular development beyond 14-years-old. Most delayed puberties are
      functional. Congenital hypogonadotrophic hypogonadism are rare. Turner syndrome
      is the most frequent hypergonadotrophic hypogonadism in girls. The delayed
      puberty treatment is hormonal replacement. Delayed puberty clearly has a genetic
      component, and new advances in genetic research may provide tools to aid our
      understanding of the factors that regulate the timing of puberty.

PMID- 18714654
TI  - [Psychosocial implications of variations in pubertal timing].
AB  - The interrelations between pubertal timing and psychosocial maturation are
      discussed in three perspectives: the consequences of abnormally precocious or
      delayed puberty on psychosocial functioning; the impact of lower (early) or upper
      (late) borderline normal timing of puberty on adolescent exploratory behaviors;
      and the study of variations in age at onset of puberty in adolescents involved in
      delinquency.

PMID- 18714655
TI  - [Human evolution and variation in puberty onset].

PMID- 18714656
TI  - [Patient education handout: Turner syndrome].

PMID- 18714657
TI  - [A curve for post 2008].

PMID- 18714658
TI  - [Acute fever in children--infectious syndrome severity criteria. Part I:
      children].

PMID- 18714659
TI  - [Contraception].

PMID- 18714660
TI  - [Metabolic and respiratory acidosis].

PMID- 18714661
TI  - [Nutritional problems in the child and the adult].

PMID- 18714662
TI  - [Alfred Le Petit: caricature in the Hotel-Dieu hospital ].

PMID- 18714663
TI  - Is anybody out there?

PMID- 18714664
TI  - Knowledge and attitudes about smoking and environmental tobacco smoke: a
      comparison of parents and children attending upper and lower income pediatric
      sites.
AB  - To define differences in knowledge and attitudes about environmental tobacco
      smoke (ETS) and smoking among different populations of parents and children,
      surveys about smoking and health were administered in low-income pediatric
      clinics and upper-income private practices using a Likert scale. Sixty-five
      children and 300 parents from pediatric clinics and 149 children and 300 parents
      from private practices participated. At the clinics 39% of parents were white,
      23% graduated college, 33% smoked, and 20% allowed smoking in their home. This
      differed from private practices where 93% of parents were white, 77% graduated
      college, 13% smoked and 6% allowed smoking in their home. Parents from private
      practices expressed greater agreement with fact and opinion statements about ill
      effects of tobacco. More lower income children reported living with a smoker (45%
      vs 23%). These data demonstrate differences in adult knowledge and attitudes
      about health effects of smoking, highlighting the need for increased intervention
      among lower income families.

PMID- 18714665
TI  - The founders of the Medical Society of Delaware. Doctor Nathaniel Luff.

PMID- 18714666
TI  - The outsourcing of surgical and dental procedures.

PMID- 18714667
TI  - Questions regarding causality in presumed black cohosh hepatotoxicity.

PMID- 18714668
TI  - A preliminary gene expression profile of acute graft-versus-host disease.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of
      choice for high-risk hematological malignancies, yet a major complication
      associated with this therapy is acute graft-versus-host disease (GVHD). Despite a
      well-defined pathophysiological mechanism, there are no definitive markers for
      predicting acute GVHD development or progression to advanced stages. In the
      current study, we enrolled four acute GVHD and four acute GVHD-free recipients of
      allogeneic HSCT and collected peripheral blood just prior to onset of clinical
      acute GVHD for analysis on Affymetrix GeneChip Human Genome U133 Plus 2.0
      microarrays. We noted significant differences in expression of 1,658 genes
      between control and acute GVHD patients, based on an analysis of covariance
      (ANCOVA) by type of transplant, a pooled error estimate, and a false discovery
      rate (FDR) of 10%. In conclusion, we offer the first report of a preliminary
      molecular signature of acute GVHD in allogeneic HSCT patients.

PMID- 18714669
TI  - Prenatal tolerance induction: relationship between cell dose, marrow T-cells,
      chimerism, and tolerance.
AB  - It was reported that the dose of self-antigens can determine the consequence of
      deletional tolerance and donor T cells are critical for tolerance induction in
      mixed chimeras. This study aimed at assessing the effect of cell doses and marrow
      T cells on engraftment and tolerance induction after prenatal bone marrow
      transplantation. Intraperitoneal cell transplantation was performed in FVB/N (H
      2K(q)) mice at gestational day 14 with escalating doses of adult C57BL/6 (H
      2K(b)) marrows. Peripheral chimerism was examined postnatally by flow cytometry
      and tolerance was tested by skin transplantation. Transplantation of light
      density marrow cells showed a dose response. High-level chimerism emerged with a
      threshold dose of 5.0 x 10(6) and host leukocytes could be nearly replaced at a
      dose of 7.5-10.0 x 10(6). High-dose transplants conferred a steady long-lasting
      donor-specific tolerance but were accompanied by >50% incidence of graft-versus
      host disease. Depletion of marrow T cells lessened graft-versus-host disease to
      the detriment of engraftment. With low-level chimerism, tolerance was a graded
      phenomenon dependent upon the level of chimerism. Durable chimerism within 6
      months required a threshold of > or = 2% chimerism at 1 month of age and
      predicted a 50% chance of long-term tolerance, whereas transient chimerism (<2%)
      only caused hyporesponsiveness to the donor. Tolerance induction did not succeed
      without peripheral chimerism even if a large amount of injected donor cells
      persisted in the peritoneum. Neither did an increase in cell doses or donor T
      cell contents benefit skin graft survivals unless it had substantially improved
      peripheral chimerism. Thus, peripheral chimerism level can be a simple and
      straightforward test to predict the degree of prenatal immune tolerance.

PMID- 18714670
TI  - Improved xenogenic hepatocyte implantation into nude mouse liver parenchyma with
      acute liver failure when followed by repeated anti-Fas antibody (Jo2) treatment.
AB  - Hepatocyte transplantation is a promising therapy for acute liver failure in
      humans. Recently, we succeeded in inducing various acute and chronic liver
      failures in nude mice. Engraftment of transplanted xenogeneic rat hepatocytes,
      visualized in the host liver by anti-MHC class I immunohistochemistry, revealed
      that liver repopulation was limited, and equivalent in nude mice with and without
      acute liver failure. In the present study, acute liver failure was induced in
      nude mice by a single injection of sublethal anti-Fas antibody Jo2, followed 24 h
      later by rat hepatocyte transplantation and than by a weekly repeated injection
      of Jo2. Rat hepatocyte engraftment into the recipient liver parenchyma 3 weeks
      following hepatocyte transplantation was about sevenfold increased when nude mice
      were subsequently subjected to weekly repeated Jo2 injection. Genomic analysis of
      these mice showed an overall transcriptome profile of upregulation of cellular
      cycle blocking transcripts, activation of liver injury inducing IFN-gamma/STAT1
      pathway, and circadian transcript signature of antiproliferative cell status
      compared to mice submitted to hepatocyte transplantation only. The findings of
      the present study suggest that the induction of cell proliferation blockade in
      recipient livers could promote sufficient engraftment of transplanted hepatocytes
      to allow transient or definitive treatment of liver failure in humans.

PMID- 18714671
TI  - Sertoli cell line lacks the immunoprotective properties associated with primary
      Sertoli cells.
AB  - Sertoli cells are important for maintenance of the immune privileged environment
      of the testis and prolong survival of cotransplanted cells. The objective of the
      current study was to examine the immunoprotective properties of a mouse Sertoli
      cell line (MSC-1) in order to identify a Sertoli cell line that could be used to
      aid in investigation of the immunoprotective abilities of Sertoli cells. BALB/c
      islets were cotransplanted with 0-9 million primary BALB/c Sertoli cells or MSC-1
      cells into diabetic C3H or BALB/c mice and protection of grafted islets was
      examined by monitoring blood glucose levels and immunohistochemical analysis.
      Additionally, expression of potential immunoprotective factors in MSC-1 cells was
      examined. Cotransplantation of islets with 3 million primary Sertoli cells
      significantly prolonged islet allograft survival (61.1 +/- 6.9 days; p < 0.05)
      compared with control mice that received allogeneic islets alone (26.9 +/- 2.1
      days). Grafts collected from normoglycemic C3H mice at 100 days posttransplant
      contained insulin-positive beta-cells adjacent to allogeneic Sertoli cells
      arranged in tubule-like structures. In contrast, cotransplantation of islet
      allografts with MSC-1 cells did not prolong islet survival (average 29.8 +/- 3.3
      days) regardless of the number of MSC-1 cells transplanted and the rejected
      grafts contained very few beta-cells and randomly arranged MSC-1 cells. The lack
      of islet cell survival was not due to detrimental effects of MSC-1 cells because
      syngneic islets cotransplanted with MSC-1 cells were functional throughout the
      study. MSC-1 cells were found to express known Sertoli cell-expressed,
      immunoprotective factors, clusterin, Fas ligand, and transforming growth factor
      beta1, suggesting additional factors may be involved in Sertoli cell immune
      privilege. These data indicate the MSC-1 cell line lacks the immunoprotective
      properties associated with primary Sertoli cells. Further study of this cell line
      could be useful in examining the mechanisms that enable Sertoli cells to provide
      immune privilege.

PMID- 18714672
TI  - A rat embryo staging scale for the generation of donor tissue for neural
      transplantation.
AB  - In rat models of Parkinson's and Huntington's diseases, embryonic neural cells
      obtained from embryos of specified ages can be implanted into the brain to
      partially restore both physiology and function. However, in litters produced
      using overnight mating protocols (often from commercial suppliers), the embryonic
      age can be difficult to determine precisely. As a result, embryonic size based on
      crown to rump length (CRL) is usually a more reliable method of embryo staging
      than the day of mating. This approach is not without difficulty. There are a
      number of rat staging scales in the literature, none of which deal with donor
      ages younger than E13, and there are discrepancies between scales at some donor
      ages. In the present article, we have devised a short mating-period protocol to
      produce precisely aged embryos. We show that CRL is a highly accurate,
      reproducible index of donor age and we present an updated embryonic staging scale
      for Sprague-Dawley (CD) rats that includes donor ages younger than those
      previously reported.

PMID- 18714673
TI  - Electrical stimulation-induced release of beta-endorphin from genetically
      modified neuro-2a cells.
AB  - The quantity of therapeutic gene products released from genetically engineered
      cells can be controlled externally at different levels. The widely used approach
      of controlling expression, however, generally has the disadvantage that chemical
      substances must be applied for stimulation. An alternative strategy aims at
      controlling gene products at posttranslational levels such as secretion. The
      secretion of a therapeutic agent can be regulated if the agent is targeted to the
      regulated secretory pathway and stored in the secretory granules until its
      release. In this article we address the question of whether the release of beta
      endorphin, an opioid with a potent analgesic effect, could be induced by
      electrically stimulating stably transfected Neuro-2a cells. Throughout this study
      we used the human proopiomelanocortin (POMC) gene, which is the precursor
      molecule for human beta-endorphin. We analyzed its subcellular localization and
      found it in the regulated secretory pathway in Neuro-2a cells. Using electrical
      field stimulation we were able to identify a stimulation pattern that
      significantly increased the release of beta-endorphin-immunoreactive material,
      although to a limited extent. This result indicates that electrical stimulation
      of secretion could be used to manipulate the amount of a therapeutic agent
      released from transplanted cells.

PMID- 18714674
TI  - Comparison of human serum with fetal bovine serum for expansion and
      differentiation of human synovial MSC: potential feasibility for clinical
      applications.
AB  - The aim of this study was to evaluate the effect of human serum (HS) on growth
      and differentiation capacity of human synovium-derived mesenchymal stem cells
      (MSC) in comparison to cells grown in fetal bovine serum (FBS). Human MSCs were
      isolated from the synovium of knee joints of three donors and the cells were
      cultured individually in varying concentrations of allogenic HS or FBS. Bovine
      MSCs were isolated from synovium and cultured in the same manner. Cell
      proliferation was assessed by the tetrazolium assay after passage 3. The capacity
      for chondrogenic and osteogenic differentiation was investigated in specific
      media followed by 1,9-dimethylmethylene blue assay and alcian blue staining, or
      by alizarin red staining, respectively. Human MSCs proliferated significantly
      more rapidly in the presence of HS than with equivalent levels of FBS.
      Chondrogenic or osteogenic differentiation occurred to nearly identical levels in
      HS or FBS. The results of this study indicate that HS is superior for the culture
      of human MSCs compared with FBS in terms of cellular expandability, without
      losing chondrogenic or osteogenic differentiation capacity. Coupled with the
      advantage in eliminating the potential risk accompanied with the use of xeno
      derived materials, pooled, well-characterized HS could be a useful reagent to
      promote cellular expansion for clinical synovial stem cell-based therapy.

PMID- 18714675
TI  - Riboflavin inhibits IL-6 expression and p38 activation in islet cells.
AB  - Riboflavin is a water-soluble vitamin that reduces the production of
      proinflammatory mediators and oxygen radicals. Because islet beta-cells are very
      sensitive to oxidative stress and to cytokines, we investigated the possible
      cytoprotective effects of riboflavin on insulinoma NIT-1 cells and on isolated
      rodent islets. NIT-1 cells and islets cultured in the presence or absence of 10
      microM riboflavin were studied at baseline and after exposure to cytokines (TNF
      alpha, IL-1beta, INF-gamma). Riboflavin treatment did not affect islet cell
      viability as assessed by flow cytometry for caspases activation. However,
      riboflavin prevented the cytokine-induced increase in IL-6 mRNA expression and
      p38 phosphorylation analyzed by real-time PCR and immunoassay, respectively. In
      summary, nontoxic doses of riboflavin prevent cytokines-induced p38
      phosphorylation and IL-6 upregulation in islet cells. This observation, together
      with the safety profile of riboflavin in the clinical setting, makes it an
      appealing agent for islet cytoprotection in islet transplantation protocols.

PMID- 18714676
TI  - Improved glucose regulation on a low carbohydrate diet in diabetic rats
      transplanted with macroencapsulated porcine islets.
AB  - Islet xenografts from porcine donors can reverse diabetes in experimental animal
      models and may be an alternative to human islet transplantation. We have recently
      reported the ability of porcine islets encapsulated in a double layer of
      hydrophilic agarose to maintain in vitro functional ability for >6 months.
      Although beta-cells are capable of adapting their secretory capacity in response
      to glucose levels, evidence has shown that prolonged hyperglycemia can compromise
      this ability. The aim of the present study was to determine the effects of diet
      manipulation on the long-term regulation of blood glucose levels, and the
      preservation of functional islet in the macrobeads. Twenty-one streptozotocin
      induced diabetic Wistar-Furth male rats were randomly assigned to two diets
      containing 64% carbohydrate (CHO) or 20% CHO. Groups of five to six animals
      assigned to either diet were implanted with either empty (EM) or porcine islet
      containing macrobeads (PIM) and followed for 333 days. Observations included
      general condition, body weight, blood glucose, and food and water intakes.
      Monthly blood samples were collected for insulin and C-peptide analysis. The 20%
      CHO diet significantly lowered blood glucose values when compared with those of
      the 64% CHO groups for both the empty (14.94 +/- 0.41 vs. 16.26 +/- 0.42 mmol/L,
      respectively, p < 0.001) and islet macrobead recipients (12.88 +/- 0.39 vs. 15.57
      +/-0.85 mmol/L, respectively, p <0.001). The different diets, however, had no
      statistically significant effects on the preservation of islet mass in the
      macrobead. Serum porcine C-peptide was detected throughout the experiment in
      animals receiving porcine islet macrobeads, regardless of diet. Diabetic rats fed
      a low carbohydrate level diet and transplanted with porcine islet macrobeads had
      improved total tissue glucose disposal and improved clinical parameters
      associated with diabetes.

PMID- 18714677
TI  - Efficient delivery of human single fiber-derived muscle precursor cells via
      biocompatible scaffold.
AB  - The success of cell therapy for skeletal muscle disorders depends upon two main
      factors: the cell source and the method of delivery. In this work we have
      explored the therapeutic potential of human muscle precursor cells (hMPCs),
      obtained from single human muscle fibers, implanted in vivo via micropatterned
      scaffolds. hMPCs were initially expanded and characterized in vitro by
      immunostaining and flow cytometric analysis. For in vivo studies, hMPCs were
      seeded onto micropatterned poly-lactic-glycolic acid 3D-scaffolds fabricated
      using soft-lithography and thermal membrane lamination. Seeded scaffolds were
      then implanted in predamaged tibialis anterior muscles of CD1 nude mice; hMPCs
      were also directly injected in contralateral limbs as controls. Similarly to what
      we previously described with mouse precursors cells, we found that hMPCs were
      able to participate in muscle regeneration and scaffold-implanted muscles
      contained a greater number of human nuclei, as revealed by immunostaining and
      Western blot analyses. These results indicate that hMPCs derived from single
      fibers could be a good and reliable cell source for the design of therapeutic
      protocols and that implantation of cellularized scaffolds is superior to direct
      injection for the delivery of myogenic cells into regenerating skeletal muscle.

PMID- 18714678
TI  - Histopathological and ultrastructural features of Koi herpesvirus (KHV)-infected
      carp Cyprinus carpio, and the morphology and morphogenesis of KHV.
AB  - Epizootics of Koi herpesvirus (KHV) cause mass mortalities in koi carp and common
      carp worldwide. We used a newly developed 'per-gill infection' procedure with
      live KHV, and then conducted detailed histopathological and ultrastructural
      studies of KHV-infected cells including an examination of the morphology and
      morphogenesis of KHV. The primary target of KHV was respiratory epithelial cells
      of the gill lamellae, and release of virions from infected epithelial cells
      resulted in a systemic infection affecting the kidney, spleen, heart, brain and
      liver. The pathognomonic feature of infected cells was the formation of
      intranuclear inclusion bodies with marginal hyperchromatosis in the nucleus.
      Within the nucleus, assembly of capsids and nucleocapsids and an increase in
      filamentous nucleoproteins were evident. Enveloped nucleocapsids budded from the
      inner nuclear membrane into the perinuclear space. De-enveloped nucleocapsids
      were translocated in the cytoplasm to be embedded within inclusion bodies where
      tegumentation of the nucleocapsid occurred. Enveloped virions that had budded
      into intracytoplasmic vesicles and virions located extracellularly were composed
      of an electron-dense core, surrounded in turn by the capsid, the tegument and
      finally an envelope with projections. The morphology and morphogenesis of KHV
      were the same as those of viruses within the family Herpesviridae.

PMID- 18714679
TI  - Immunohistochemistry of Atlantic cod larvae Gadus morhua experimentally
      challenged with Vibrio anguillarum.
AB  - Farming of Atlantic cod Gadus morhua is one of the most rapidly growing sectors
      of Norwegian aquaculture. Classical vibriosis caused by Vibrio anguillarum is a
      problem in cod aquaculture. To prevent disease outbreaks, a thorough
      understanding of the infection route and the impact of the bacteria on the host
      is important. The intestinal tract, skin and gills have all been proposed as
      routes of entry for bacterial infections such as vibriosis. We aimed to further
      develop understanding of V anguillarum serotype O2alpha infections in cod larvae
      by elucidation of a possible route of entry, the pattern of infection and its
      histopathology. Cod eggs were transferred to a 24-well polystyrene multi-dish
      with 2 ml of sterile aerated 80% (28 per thousand salinity) seawater. Challenge
      doses were 10(4) and 10(6) CFU ml(-1). Unchallenged larvae were used as controls.
      Larvae for immunohistochemical examination were sampled daily from each group. In
      most of the larvae, either no or very few bacteria were observed. Typical
      findings were clusters of bacteria in the spaces between the primary gill
      lamellae. None of these bacteria seemed to have adhered to the gills. Intestines
      of 3 out of 161 larvae examined contained positively immunostained bacteria. Some
      bacteria appeared attached to the microvilli, but none was observed inside
      epithelial cells. Only 2 larvae from the low-challenge dose group showed clear
      signs of histopathology, which occurred in the intestine. It is not possible to
      draw any conclusions regarding the portal of entry.

PMID- 18714680
TI  - Eye fluke infection and lens size reduction in fish: a quantitative analysis.
AB  - Parasites have a variety of harmful effects on their hosts, some of which may be
      overlapping or complementary and thus easily overlooked but which are still
      important for the overall severity of infection. We investigated the effect of
      Diplostomum sp. eye fluke infection on the size of the eye lens in a range of
      wild and farmed fish species and those exposed to controlled parasite infection.
      We found that asymmetry in intensity of infection between the right and left lens
      of an individual fish affected lens size such that the lens with the higher
      intensity of infection was smaller. Interestingly, however, this was observed
      only in 3 of the 10 species studied (whitefish, smelt and sea trout) although in
      these 3 species the effect had already became evident at low intensities of
      infection. Furthermore, the average lens size was significantly smaller in
      experimentally exposed whitefish Coregonus lavaretus with a higher intensity of
      infection than the controls, emphasising the sensitivity of this species to
      parasite-induced changes in lens size. Reduction in lens size may contribute to
      the deleterious effects of cataract formation by intensifying the effects of
      individual parasites in the lens. It may also directly affect the overall optical
      performance of the lens and already impair host vision at low intensities of
      infection.

PMID- 18714681
TI  - First report of a Mikrocytos-like parasite in European oysters Ostrea edulis from
      Canada after transport and quarantine in France.
AB  - As part of a disease resistance experiment, 112 apparently healthy European flat
      oysters Ostrea edulis L. were exported from Canada (Nova Scotia) into France to
      test their susceptibility to Bonamia ostreae infection. Twelve oysters died in
      transit and 17 others died within 2 wk of laboratory quarantine acclimation. All
      oysters were examined histologically, and the 17 that died during quarantine were
      assayed for microcells (Bonamia sp. and Mikrocytos mackini) using molecular
      techniques. A microcell parasite was detected in the connective tissue of 5 of
      the 112 oysters. Morphological appearance, tissue affinity and molecular
      characterization through PCR, in situ hybridization (ISH), fluorescence in situ
      hybridization (FISH) and sequencing revealed a protist related to M. mackini.
      This is the first report of a parasite of the genus Mikrocytos in a species
      belonging to the genus Ostrea from the Atlantic Ocean.

PMID- 18714682
TI  - Association and distribution of the ciliate Orchitophrya stellarum with asteriid
      sea stars on the west coast of North America.
AB  - The association of the scuticociliate Orchitophrya stellarum with 3 species of
      asteriid sea stars from the west coast of North America was studied by flushing
      the gonopore region with seawater and spawning the sea stars, along a latitudinal
      gradient of 2549 km between Pigeon Point, California, and Kodiak, Alaska.
      Asterias forbesii and A. rubens from the Isles of Shoals, New Hampshire (east
      coast), were also sampled. The ciliate was found on the aboral surface of both
      sexes of reproductively ripe Evasterias troschelii, Leptasterias spp., and
      Pisaster ochraceus with a maximum intensity of association occurring at Cape
      Arago, Oregon, and Clallum Bay and Manchester Dock, Washington. A survey of gonad
      smears and hematoxylin and eosin-stained sections indicated that the ciliate was
      only present in males. Spring-spawning E. troschelii and P. ochraceus are more
      negatively impacted by the ciliate than are winter-spawning Leptasterias spp. as
      judged by a skewed sex ratio and sex size differences, which may be associated
      with seasonal differences in water temperature affecting the growth rate of O.
      stellarum. The external morphology of O. stellarum appears to be similar
      throughout the geographical range surveyed.

PMID- 18714683
TI  - Renal oxalosis in free-ranging green turtles Chelonia mydas.
AB  - Eighteen green turtles Chelonia mydas recovered from the Atlantic and Gulf coasts
      of Florida and Tortuguero National Park, Costa Rica, were diagnosed with renal
      oxalosis by histopathological examination. Affected sea turtles included 14
      adults and 4 immature animals, which comprised 26% (18/69) of green turtle
      necropsy cases available for review. Calcium oxalate deposition ranged from small
      to moderate amounts and was associated with granuloma formation and destruction
      of renal tubules. All affected turtles died from traumatic events or health
      problems unrelated to renal oxalosis; however, 1 immature turtle had notable
      associated renal injury. Crystal composition was confirmed by infrared and
      scanning electron microscopy and energy dispersive X-ray analysis. The source of
      calcium oxalate is unknown and is presumed to be of dietary origin.

PMID- 18714684
TI  - Mortality of discards from southeastern Australian beach seines and gillnets.
AB  - Two experiments were done in an Australian estuary to quantify the mortalities
      and contributing factors for key species discarded during 8 and 9 deployments of
      commercial beach (or shore) seines and gillnets, respectively. In both
      experiments, bycatches (2347 individuals comprising 16 species) were handled
      according to conventional practices and assessed for immediate mortalities before
      live samples of selected species were discarded into replicate cages along with
      appropriate controls, and monitored for short-term mortalities (< or =10 d). All
      of the seined or gilled fish were alive prior to discarding. During the beach
      seine experiment, 20% of caged seined-and-discarded surf bream Acanthopagrus
      australis (n = 290) were dead after 5 d, with most mortalities occurring between
      the second and fifth day. In the gillnet experiment, 42 and 11% of gilled-and
      discarded A. australis (n = 161) and lesser salmon catfish Neoarius graeffei (n =
      67), respectively, died during a 10 d monitoring period, mostly within the first
      5 d. There were no deaths in any controls for these fish. Mixed-effects logistic
      models revealed that the mortality of A. australis discarded from both gears was
      significantly (p < 0.01) and negatively correlated with their total length, while
      N. graeffei had a significantly (p < 0.05) greater (5-fold) probability of dying
      when jellyfish Catostylus sp. were present in the gillnet. Simple modifications
      to the operations of beach seines and gillnets and/or post-capture handling
      procedures, such as close regulation of size selectivity for the target species,
      careful removal of fish from meshes, and abstention from setting during high
      abundances of jellyfish will maximise the survival of discarded bycatch.

PMID- 18714685
TI  - Sodium hypochlorite denatures the DNA of the amphibian chytrid fungus
      Batrachochytrium dendrobatidis.
AB  - Batrachochytrium dendrobatidis, an aquatic amphibian fungus, has been implicated
      in many amphibian declines and extinctions. A real-time polymerase chain reaction
      (PCR) TaqMan assay is now used to detect and quantify B. dendrobatidis on
      amphibians and other substrates via tissue samples, swabbing and filtration. The
      extreme sensitivity of this diagnostic test makes it necessary to rigorously
      avoid cross-contamination of samples, which can produce false positives. One
      technique used to eliminate contamination is to destroy the contaminating DNA by
      chemical means. We tested 3 concentrations of sodium hypochlorite (NaOCl) (1, 6
      and 12%) over 4 time periods (1, 6, 15 and 24 h) to determine if NaOCl denatures
      B. dendrobatidis DNA sufficiently to prevent its recognition and amplification in
      PCR tests for the fungus. Soaking in 12% NaOCl denatured 100% of DNA within 1 h.
      Six percent NaOCl was on average 99.999% effective across all exposure periods,
      with only very low numbers of zoospores detected following treatment. One percent
      NaOCl was ineffective across all treatment periods. Under ideal, clean conditions
      treatment with 6% NaOCl may be sufficient to destroy DNA and prevent cross
      contamination of samples; however, we recommend treatment with 12% NaOCl for 1 h
      to be confident all B. dendrobatidis DNA is destroyed.

PMID- 18714686
TI  - Improvement of a PCR method for the detection of necrotizing hepatopancreatitis
      in shrimp.
AB  - Necrotizing hepatopancreatitis (NHP) is considered to be one of the most
      important bacterial diseases affecting penaeid shrimp culture and is caused by an
      unclassified Gram-negative, pleomorphic, intracellular Alphaproteobacterium. Due
      to the enteric nature of the bacteria, PCR is the one non-lethal method available
      for detection of the pathogen. Over a decade ago, a PCR protocol was developed
      for detection of NHP, which over the subsequent years was shown to occasionally
      generate false positive reactions. The University of Arizona Aquaculture
      Pathology Laboratory has developed a set of primers and PCR cycling parameters
      that have been tested on a variety of DNA templates, using 2 types of PCR reagent
      systems, which eliminated the generation of false positive amplicons.

PMID- 18714688
TI  - Misuse of PCR assay for diagnosis of mollusc protistan infections.
AB  - Polymerase chain reaction (PCR) assays are useful tools for pathogen
      surveillance, but they are only proxy indications of pathogen presence in that
      they detect a DNA sequence. To be useful for detection of actual infections, PCR
      assays must be thoroughly tested for sensitivity and specificity, and ultimately
      validated against a technique, typically histology, which allows visualization of
      the parasite in host tissues. There is growing use of PCR assays for pathogen
      surveillance, but too often the assumption is made that a positive PCR result
      verifies an infection in a tested host. This assumption is valid only if the
      assay has been properly validated for the geographic area and for the hosts
      examined. Researchers should interpret unvalidated PCR assay results with
      caution, and editors and reviewers should insist that robust validations support
      all assertions that PCR results confirm infections.

PMID- 18714687
TI  - Tissue changes in the shore crab Carcinus maenas as a result of infection by the
      parasitic barnacle Sacculina carcini.
AB  - We studied the effect of parasitic invasion by the barnacle Sacculina carcini on
      shore crabs Carcinus maenas collected from the Menai Straits in North Wales, UK.
      A significant reduction in serum protein and circulating granular, semi-granular
      and hyaline blood cells was observed in parasitised individuals, while serum
      ammonium and glucose concentrations were significantly increased. No difference
      in hepatopancreatic glycogen concentration was found between healthy and
      parasitised crabs. Histological analysis showed the apparent removal of fibrillar
      protein from infected muscle by the parasite. Hepatopancreas tubule necrosis was
      also routinely observed in infected individuals. Parasitisation by S. carcini
      dramatically affects the haemocyte population and serum chemistry of infected
      crabs.

PMID- 18714689
TI  - A new mind-set for nurses.

PMID- 18714690
TI  - Hacking shock.

PMID- 18714691
TI  - Patient satisfaction. Hospitals tap into a niche market: executive health.

PMID- 18714692
TI  - Telemedicine. Without leaving the city, pharmacists fill void at rural hospitals.

PMID- 18714693
TI  - Other voices. Is health care ready for Google? Interview by Matthew Weinstock.

PMID- 18714694
TI  - Practical ethics. Will bad news slow transparency?

PMID- 18714695
TI  - Storyboard. Leaving the ED, without a long wait.

PMID- 18714696
TI  - Security. Responding to violence requires a reasoned, not emotional, response.

PMID- 18714697
TI  - Workforce. Federal agency plans to assess worker safety practices at hospitals.

PMID- 18714699
TI  - Policy. Medicaid cost-cutting rules may be shelved.

PMID- 18714700
TI  - Getting IT right.

PMID- 18714701
TI  - Are patients happier at most wired hospitals?
AB  - The results are in from H&HN's 10th annual Most Wired Survey and Benchmarking
      Study, and analyses of the data indicate that patients favor hospitals and health
      systems with advanced information technology. Moreover, among this year's 100
      Most Wired organizations, quality outcomes--including risk-adjusted mortality
      rates--are better than among hospitals in general. Our fold-out section includes
      the top 100 list.

PMID- 18714702
TI  - Reining in RAC.
AB  - The much-dreaded Medicare recovery audit contractor program is scheduled to go
      nationwide this fall. Hospitals hope the most onerous aspects from the RAC pilot
      project will be gone by then.

PMID- 18714703
TI  - A new model for hospital design rises in an Ohio cornfield.
AB  - Emerging from a cornfield in Ohio, Dublin Methodist Hospital uses evidence-based
      design to create an impressive new facility that is both beautiful and brainy.

PMID- 18714704
TI  - Who sets the standards for bariatric care?
AB  - Critics say too many organizations offer certification for bariatric programs,
      confusing consumers. Some providers also complain that certification puts too
      much emphasis on the volume of surgeries performed.

PMID- 18714705
TI  - The 2008 AHA NOVA Awards.
AB  - The five winners of this year's AHA NOVA Awards partner with other organizations
      within their communities to tackle some of the most pressing health and social
      problems.

PMID- 18714706
TI  - Datapage. Health care's biggest challenge.

PMID- 18714707
TI  - Quality update. Working within the community.

PMID- 18714708
TI  - Can seniors afford care?

PMID- 18714709
TI  - Contextual factors and health risk behaviors associated with date fighting among
      high school students.
AB  - Over 2,000 North Carolina high school students completed surveys measuring
      community risk and protective factors and individual health risk behaviors
      including dating violence perpetration and victimization. Females reported more
      date fighting perpetration than males (8.8% to 4.0%), as well as greater levels
      of date fighting victimization (7.2% and 5.0%). In multivariate models, factors
      associated with date fighting perpetration among females and males included
      riding with a drinking driver. Neighborhood organization was protective for both
      groups. Cigarette use, drinking and driving, and being a minority were also
      associated with perpetration among females, while tobacco use was associated with
      date fighting perpetration by males. Factors associated with victimization among
      both genders included riding with a drinking driver. Females were more likely to
      be victimized if they used marijuana, whereas males were less likely to be a
      victim of date fighting if they perceived their community to be "organized."
      Findings reflect comparable individual risk factors for date fighting across
      genders, with few exceptions, and warrant further investigation of the role of
      community assets in protecting young people from dating violence.

PMID- 18714710
TI  - Perceptions of cervical cancer threat, benefits, and barriers of Papanicolaou
      smear screening programs for women in Iran.
AB  - OBJECTIVES: The main purpose was to assess associations between HBM variables and
      participation in cervical cancer screening programs in a sample of Iranian women.
      METHODS: A total of 333 married women of childbearing age were recruited with
      cluster sampling. The study was conducted from spring 2002 to spring 2003 and a
      self-report questionnaire and structured interview were designed to measure the
      four HBM constructs and Iranian women's knowledge about Pap smear screening.
      RESULTS: A total of 68.5% reported having undergone at least one Pap test. Women
      were more likely to participate in Pap smears when they had access to knowledge
      about cervical cancer and screening programs. Furthermore, the perceived benefit
      and barrier variables of the Health belief model were two factors related to
      participation in Pap smear testing. CONCLUSIONS: Health care professionals must
      provide women with more information about cervical cancer and the benefits of
      participating in cervical cancer screening programs.

PMID- 18714711
TI  - The role of behavioral, normative and control beliefs in breast self-examination.
AB  - CONTEXT: A limited number of studies have been conducted examining the role of
      beliefs in the prediction of breast self-examination (BSE) behavior in Australian
      women, particularly women under 50 years of age for which it is the primary
      method of early detection of breast cancer. OBJECTIVE: The present research
      investigated the differences in behavioral, normative and control beliefs between
      BSE performers and non-performers, within a theory of planned behavior framework,
      to assist in the development of specific education programs aimed at increasing
      BSE amongst this demographic group. METHOD: Two hundred and fifty-three women
      enrolled in an undergraduate psychology course completed a questionnaire
      assessing beliefs regarding BSE. One month later, these women reported their BSE
      behavior during the previous month. Multivariate analyses were performed to
      identify belief-based differences between BSE performers and non-performers.
      RESULTS: Underlying behavioral and control, but not normative, beliefs about BSE
      distinguished between BSE performers and non-performers. Performers were more
      likely than non-performers to believe that engaging in BSE would be associated
      with identifying a lump or breast change sooner and detecting a breast cancer
      earlier in its course. Non-performers were more likely to perceive factors such
      as forgetting to perform the behavior, lack of time, lack of knowledge about how
      to perform the behavior, laziness, and a lack of confidence in their ability to
      identify lumps and breast changes as factors preventing their control over the
      performance of BSE. CONCLUSIONS: The belief-based differences between BSE
      performers and non-performers found in this study can be used to inform health
      promotion strategies aimed at increasing BSE behavior in women less than 50 years
      of age.

PMID- 18714712
TI  - A complex negotiation: women's experiences of naming and not naming premenstrual
      distress in couple relationships.
AB  - Recent research has demonstrated the importance of family relationships in
      women's experience of premenstrual changes, their construction of these changes
      as "PMS." However, the discursive process by which women take up the subject
      position of "PMS" sufferer through the explicit naming of "PMS" to an intimate
      partner has received little research attention. Drawing on 60 individual
      interviews with Australian women, conducted between 2004 and 2006, we examined
      accounts of naming "PMS" in intimate relationships, women's explanations for
      naming or not naming, their experiences of their partner naming them as
      premenstrual. The analysis process identified an overarching theme of naming
      "PMS," which was made up of three themes: naming to explain; "PMS" becoming the
      only explanation for distress; "PMS" as not a legitimate explanation for
      distress. The findings suggest that clinicians need to be aware of women's
      complex, often ambivalent, experiences of naming "PMS" within their
      relationships, when working with women, couples, seeking treatment or support for
      premenstrual distress.

PMID- 18714713
TI  - Feasibility of gaining access to women in jail for health interventions.
AB  - Female jail populations are comprised of women at high-risk for an array of
      psychological and physical health problems. Jails offer an opportune site to
      deliver clinical health interventions to women who often quickly cycle back into
      the community. In contrast with prison population studies, many investigators
      have encountered recruitment problems when attempting to engage the jailed
      population in clinical research. This study addressed the feasibility of
      recruiting detained women for eligibility for clinical research. METHODS:
      Commitments to the Women's Facility at the Rhode Island Department of Corrections
      were chronicled for 40 months, from February 2004 to June 2007. Research staff,
      working 8 a.m. to 5 p.m., Monday through Friday, attempted to screen all detained
      women for a randomized clinical trial. RESULTS: During the 40-month study period,
      4,131 individual women had 8,010 commitments to the facility. Staff was able to
      gain access to nearly 50% of women. Of the inaccessible women, 65% were released
      in less than 24 hours. In total, 88% of accessed women agreed to be screened for
      study participation. No significant differences were observed by race/ethnicity
      or age between women who were screened and those who were not. CONCLUSIONS:
      Clinical research with the female jail population is feasible. The jail setting
      requires researchers to plan for short-commitment lengths and high rates of
      recidivism to optimize screening and recruitment in this population.

PMID- 18714714
TI  - Correlates of mental health service use among lesbian, gay, and bisexual mothers
      and prospective mothers.
AB  - Lesbian, gay, and bisexual women undertake parenting in a social context that may
      be associated with unique risk factors for perinatal depression. This cross
      sectional study aimed to describe the mental health services used by women in the
      perinatal period and to identify potential correlates of mental health service
      use. Sixty-four women who were currently trying to conceive, pregnant, or the
      parent of a child less than one year of age were included. One-third of women
      reported some mental health service use within the past year; 30.6% of women
      reported a perceived unmet need for mental health services in the past year, with
      40% of these women citing financial barriers as the reason for their unmet need.
      Women who were trying to get pregnant or who were less "out" were most likely to
      have had recent mental health service use. Women who had conceived by having sex
      with a man or who reported more than three episodes of discrimination were most
      likely to report unmet needs for mental health services. Providers may benefit
      from additional knowledge about the LBG social context that is relevant to
      perinatal health, and from identifying a strong referral network of skilled and
      affordable counsellors.

PMID- 18714715
TI  - Observation or inpatient? Correct patient status more critical than ever.

PMID- 18714716
TI  - Status management cuts observation patients, LOS.

PMID- 18714717
TI  - CMS proposes additional quality measures.

PMID- 18714718
TI  - Busy ED keeps promise of 'door to doc' in 31 minutes.

PMID- 18714719
TI  - Collaboration reduces LOS, improves outcomes.

PMID- 18714720
TI  - You can't assume headaches are benign.

PMID- 18714721
TI  - [Medical aspect of cosmonauts' safety during emergency landing. Respicere et
      prospicere].
AB  - Participating in the comprehensive development of the system for safe emergency
      landing in space vehicles Voskhod and Soyuz, enterprise "Zvezda" undertook an
      extensive program of technical and physiological experiments with volunteers,
      including a group of physicians, in the interest of designing personal protection
      means for space crew. Over 130 physiological pile-engine experiments with the
      impact velocity of up to 9 m/s were performed between 1963 and 1967. The article
      presents medical and biomechanical analysis of the experimental data. The central
      part of the crew safety system in the event of emergency landing is a shock
      absorbing seat with an individually molded support surface. This support surface
      ensures a uniform load distribution and also attenuates shock hardness by dint of
      own deformation. The Voskhod seat was outfitted with a pendulum hanger bracket on
      two shock-absorbers. The Soyuz seat has only one shock-absorber at the head end.
      The shock-absorber allows seat turns at high angular velocities and,
      consequently, appearance of additional mechanic and biomechanical reactions. The
      article attempts to analyze this phenomenon as well as the whole aggregate of
      human body responses onto the spacecraft impact with ground. To give readers the
      opportunity of independent conclusions from the data of the unlikely to be
      replicated experiments, the article is supplemented with graphs visualizing a
      larger part of the tests data, and their interpretations. It is aimed to help
      young specialists fill up the gap in knowledge about this medical aspect which
      remains of high topicality in many fields including safety of future piloted
      space programs.

PMID- 18714722
TI  - [Hemodynamic shifts in humans under the conditions of prolonged microgravity and
      the role of hypovolemia].
AB  - Purpose of this work was to elicit the role of hypovolemia in the development of
      hemodynamic shifts and loss of orthostatic tolerance in humans during prolonged
      space flights (PSF). Correlation analysis of the data of in-flight ultrasonic
      investigations of hemodynamics in resting cosmonauts and bio-impedance
      measurements of body liquids in different periods during PSF pointed out that
      changes in the left ventricle filling and renal artery resistance (Rren) reflect
      the degree of hypovolemia with r = 0.95. The dependence of orthostatic tolerance
      on hypovolemia fell short of this ambiguity. Lower body negative pressure tests
      (LBNP) performed by 15 cosmonauts in different periods of PSF typically
      correlated with the body hydration status at r = 0.94; however, several
      cosmonauts showed a substantial loss of LBNP tolerance despite a moderate
      hypovolemia. Therefore, we may hypothesize that hypovolemia is a significant yet
      not the sole factor in orthostatic disorders. Deconditioning, altered control of
      hemodynamics, decreased vasoconstriction of arterial vessels and increased
      compliance of the leg veins have an important, in some cases decisive role in
      degradation of orthostatic tolerance.

PMID- 18714723
TI  - [The peculiarities of defining the psychological and information characteristics
      of individuals in non-standard situations].
AB  - In some situations (e.g. long-duration experiments with human subjects, accidents
      and catastrophes) assessment of individual's ability to work or even continue
      functioning by objective criteria may have practical implications. The authors
      propose complementing the common methods of examination with a number of
      semantic, self-awareness, associative and symbolic (sign) questionnaires. Thrice
      repeated questioning was found to provide adequate results reducing the
      dispersion of data. The proposed approach was positively validated in an accident
      and showed good consistency when compared with the objective examination data.

PMID- 18714724
TI  - [Job quality evaluation with regard to individual stress tolerance of operators].
AB  - Male test-subjects (n = 8, 25 to 36 years of age) were kept awake and working for
      67 hrs. in an anechoic room. Every 1-2 hours the test-subjects performed eye
      tracking of rhythmic light points with an abrupt and unexpected change of
      frequency. The task was to strike the key the moment the frequency was noticed to
      have changed. One test session took 10 to 15 minutes; depending on test duration,
      the number of frequency change could be from 38 up to 59-60. The moments of
      frequency change and keystroke were registered. Latent reaction time was
      determined (LRT). Individual LRT values and variations (SD) were evaluated. A
      statistically significant correlation between individual LRT values and
      variations was established, i.e. high SD corresponded to high LRT values and visa
      versa. Thus the worst test results were associated with high LRT values and
      variations, whereas, on the contrary, the best test results were characterized by
      low LRT values and variations. Data of the investigation are subject to analysis
      with regard to their relation to operator's stress tolerance; possible
      neurophysiological mechanisms of this relation are discussed.

PMID- 18714725
TI  - [Optimization of directed training loads on the respiratory system].
AB  - Potentiality of an increased elastic resistance to respiratory movements in
      improving the functional conditioning of young athletes was evaluated. Training
      with increased elastic resistance to respiration brought about gains in strength
      and endurance of the respiratory muscles, growth of the maximal oxygen
      consumption, work ability, and special physical fitness of athletes.

PMID- 18714726
TI  - [Effects of short-term oxygen breathing on the human respiratory system].
AB  - Compared were effects of cryogenic and adsorptive oxygen on the respiration
      system in an experiment with 8 normal female volunteers. Mechanic impedance of
      the respiratory tract, pulmonary ventilation function, CO transport coefficient
      and physical performance were determined before and after 20 minutes of oxygen
      breathing. Breathing two types of oxygen was found to have different effects on
      the real part of mechanic impedance and the ventilatory function of the lung.

PMID- 18714727
TI  - [Physiologically active argon-based gas mixtures as a means of creating fire-safe
      gaseous environments in pressurized modules of varying purpose].
AB  - Development of acute hypoxic hypoxia in consequence of fire in various
      pressurized modules was studied. The investigation was aimed to look into the
      effects of inert argon and dramatic oxygen reduction in gaseous environment on
      animals (Wistar rats, mice c57bl/6, balb/c and f1cbaxbalb/c hybrids, Japanese
      quail embryos) and microorganism (Escherichia coli strains k-12 jf 238 and k-12
      jm 83). Also, inflammability of some widely used materials was assessed in order
      to provide inputs to developers of fire-safe gaseous mixtures for pressurized
      habitats. It was shown that argon is favorable to survivability of animals and to
      maintenance of a high level of oxygen consumption. Gaseous mixtures with oxygen
      content less than 15 volume % suppressed burning of selected materials. Results
      of the investigation offer possibilities for designing new hypoxic fire-safe gas
      mixtures that will provide adequate human performance and ensure survival in
      extreme situations.

PMID- 18714728
TI  - [Investigation of the processes of post-radiation reparation of the corneal
      epithelium cells of mice irradiated by helium ions with various LET values].
AB  - Biological effectiveness and post-radiation recovery of corneal epithelium cells
      of mice were studied. Mice were exposed to a broad range of doses from
      accelerated helium ions with the energy of 4 MeV/nucleon and 4 GeV/nucleon once
      and twice with a 24-hr. interval. LET values for these energies were 120 and 0.88
      keV/microm, respectively. Gamma-source 137Cs (LET = 0.3 keV/microm) was used as a
      radiation standard. Animals irradiated by 25-400 sGy were sacrificed in 24 and 72
      hrs. by way of cervical dislocation. Total corneal preparations made from
      enucleated eyeballs were analyzed for the mitotic index and aberrant mitoses
      using the anaphase method. High damaging properties of accelerated helium ions
      with the energy of 4 MeV/nucleon were manifested by a considerable reduction of
      the mitotic index and a more marked rise in the number of aberrant mitoses
      following the single and repeated exposure. Fractional irradiation by helium ions
      with the energy of 4 MeV/nucleon resulted in inhibition and even arrest of
      reparation suggesting additivity of separate radiation fractions. From the dose
      values that produced the double reduction of the mitotic index, coefficients of
      the relative biological effectiveness (RBE) for helium ions with the energy of 4
      MeV/nucleon and 4 GeV/nucleon were estimated to be 5.3-8.6 and 1.3-1.8,
      respectively. In the context of the number of aberrant mitoses, RBE coefficients
      were significantly lower ranging 2.3-3.5 and 1.1-1.3 for these energies,
      respectively.

PMID- 18714729
TI  - [Protective action of radioprotectors and shielding against high-energy protons
      in experiments with rats].
AB  - Experiments with male rats were staged to study effectiveness of radioprotectors
      of two classes of chemical compounds (aminothiols--cystamine and indolyl
      alkylamines--mexamine and indralin) against high-energy protons (120 MeV) at a
      minimal absolutely lethal dose (10 Gy) and more than lethal doses (11.0-14.0 Gy).
      The best protective effect was provided by intraabdominal indralin at a dose of
      75 mg/kg. However, this protective effect of indralin weakens with a dose rise
      and fades away with the dose rising to the absolutely lethal or more than lethal
      level (14.0 Gy). Investigations of the effectiveness of shielding different
      segments of the rat's body from high-energy protons (120 MeV) at more than lethal
      doses showed a substantial reduction and then full loss of the shielding
      protective action. Evaluation of the effectiveness of combined protection
      (radioprotectors plus shielding) against high-energy protons at more than lethal
      doses led to the conclusion about an additive (at 1.0-13.0 Gy) or potentiative
      (at 14.0 Gy) effect. For instance, indralin (75 mg/kg) and shielding of the
      abdomen increased rat's survivability to 89.7% after exposure at 11.0-13.0 Gy and
      to 87.5% after exposure at 14.0 Gy. It should be kept in mind that the
      radioprotective action of this combination was also observed during exposure to
      more than lethal doses when the protective effect of shielding and chemical
      compounds is minimal or lost altogether.

PMID- 18714731
TI  - [Evaluation of effectiveness of short-term orthostatic positioning of head-down
      tilted primates on the liquid body sectors].
AB  - Head-down tilting (HDT) of primates is a well-recognized model for studying the
      hypokinetic syndrome effects on the body functions. Benefits for the body liquids
      distribution of periodic transition of primates (rhesus macaques) into the
      vertical position without support loading were evaluated in a 30-d HDT
      experiment. Brief (30 to 120 minutes long, 4-5 times a week) transition from
      tilting into the vertical position had no influence on primates' hydration
      homeostasis and its infrastructure. However, the orthostatic test at the end of
      the HDT experiment showed a less increase in blood content of the lower
      extremities as compared with tilted primates that had not been periodically
      turned up into the vertical position.

PMID- 18714730
TI  - [Renal function in white rats after tiroxin injection preceded by blockade of ACE
      and nitrogen oxide].
AB  - Purpose of this work was to study renal function in white rats following a single
      dose of exogenous tiroxin (T4) on a background of non-selective NO-synthase
      blocker or inhibition of angiotensin-1 converting enzyme. The experiment was
      performed with males of outbred white rats (body mass = 140-180 g). Three days
      prior to T4 injection, the animals drank water solution of captopril (20 mg/l) or
      were injected intra-gastrically with water solution of non-selective NO-synthase
      blocker N(omega)-NLA (1 mg/100 g of body mass) over 3 days preceding T4
      injection. A single dose of sodium chloride T4 on 1% starch gel (50 microg/100 g
      of body mass) was injected intragastrically; 5% water loading was given one hour
      later. Urine and plasma samples were analyzed for osmolality; creatinine,
      nitrites, nitrates and proteins were measured in urine samples. Tirozine was
      found to moderately decrease creatinine clearance and increase excretion of
      proteins, osmotically active substances (OAS), nitrites and nitrates with urine,
      and raise concentrations of stable nitrogen oxides, primarily nitrates in blood
      plasma. Pre-block of ACE by captopril intensified diuresis and inhibited renal
      excretion of OAS, nitrites and nitrates in response to T4 injection. However,
      captopril failed to prevent the decrease in creatinine clearance and the level of
      proteinuria. Pre-block of NO synthesis resulted in marked decreases in creatinine
      clearance, excretion of OAS and nitrites, and moderation of diuresis comparing
      with intact rats and rats treated with T4 only.

PMID- 18714732
TI  - 2008 American Heart Association Statement on diagnosis, evaluation, and treatment
      of resistant hypertension: what should we remember in everyday practice?

PMID- 18714733
TI  - Should every patient with diabetes receive a statin?

PMID- 18714734
TI  - New European recommendations (European League Against Rheumatism 2008) for the
      management of lupus erythematosus: American perspective.

PMID- 18714735
TI  - Cardiovascular complications in patients with diabetic nephropathy receiving
      pharmacological versus renal replacement therapy.
AB  - INTRODUCTION: Diabetic nephropathy is a significant complication of diabetes
      mellitus and one of the major causes of renal replacement therapy. Cardiovascular
      complications are predominant causes of death in these patients. OBJECTIVES: To
      evaluate the influence of hemodialysis on cardiovascular risk factors and on
      their frequency in diabetic nephropathy patients. PATIENTS AND METHODS: 4 groups
      of renal failure patients were studied. Group 1 consisted of 71 hemodialyzed
      patients with non-diabetic nephropathy. Group 2 consisted of 29 hemodialyzed
      patients with diabetic nephropathy. Group 3 consisted of 50 patients with renal
      failure in the predialysis period (glomerular filtration rate < 60 ml/min). Group
      4 consisted of 50 non-dialyzed patients with diabetic nephropathy in the pre
      dialysis period. Complete blood count, blood gas, blood urea nitrogen,
      creatinine, glucose, lipidogram, electrolytes, parathormone, iron and dialysis
      adequacy (Kt/V) were assessed. Arterial blood pressure, resting ECG,
      echocardiography, body mass index, ankle-arm index, the prevalence of ischemic
      heart disease, myocardial infarction and chronic heart failure (NYHA
      classification) were also evaluated. RESULTS. In hemodialyzed patients with
      diabetic nephropathy lower complete blood count, less severe calcium-phosphate
      disorders, higher triglycerides and lower high-density lipoproteins cholesterol,
      with more frequent obesity, ischemic heart disease and peripheral arterial
      obstructive disease were found. Myocardial hypertrophy, cardiac arrhythmias,
      contractility disturbances, myocardial infarction and chronic heart failure were
      more common in the hemodialyzed patients, regardless of the cause of the renal
      disease. CONCLUSIONS: The risk factor for cardiovascular complications is greater
      in patients with diabetic nephropathy. Hemodialysis increases the frequency of
      cardiovascular complications in these patients and adversely affects the
      outcomes.

PMID- 18714736
TI  - Female and male chronic obstructive pulmonary disease patients with severe
      dyspnea do not profit less from pulmonary rehabilitation.
AB  - INTRODUCTION: Pulmonary rehabilitation (PR) is an established component of COPD
      management. The lack of exercise performance improvement (EPI) in severely
      dyspnoeic patients (Medical Research Council [MRC] score 5) has been questioned.
      The data on the gender impact on EPI after PR remain scarce. OBJECTIVES: The
      impact of dyspnea severity on PR outcomes was investigated and a question was
      raised whether severe dyspnea at training onset limits the profit from PR in COPD
      patients. Additionally, the impact of gender on PR results was analyzed. PATIENTS
      AND METHODS: 263 consecutive COPD patients underwent outpatient PR. Exercise
      capacity was assessed by the incremental shuttle walking test (SWT) and dyspnea
      with the MRC dyspnea score at inclusion (preSWT, preMRC) and at the end of PR
      (postSWT, postMRC). The data were analyzed in groups according to preMRC. The
      grade of improvement (deltaSWT, deltaSWT% and deltaMRC) was compared between
      groups. The influence of gender was analyzed in 138 men and 125 women. RESULTS: A
      significant absolute increase in SWT and a decrease in MRC score were shown in
      all groups and for both sexes (p < 0.05) with no significant intergroup
      differences (p > 0.05). deltaSWT% rose significantly with preMRC score and
      exceeded the values of a clinically important increase (exception: group 2 with
      preMRC score 2). No significant differences between men and women were observed
      (deltaMRC: -0.6 vs. -0.7, deltaSWT: 66.7 vs. 56.0 m, deltaSWT%: 63.7 vs. 58.1%, p
      > 0.05, respectively). CONCLUSIONS: Patients with severe dyspnea did not benefit
      less from PR. Gender did not influence PR outcome in this study.

PMID- 18714737
TI  - Activity of antioxidative enzymes and concentration of malondialdehyde as
      oxidative status markers in women with newly diagnosed Graves-Basedow disease and
      after thiamazole therapy leading to euthyroidism.
AB  - INTRODUCTION. Hyperthyroidism in the course of Graves-Basedow disease leads to
      intensification of oxidative processes and increased production of free oxygen
      radicals. It results in abnormal oxidative status of the organism. OBJECTIVES:
      Aim of this work was to assess the dynamics of oxidative status changes in women
      with Graves-Basedow disease before and after treatment with thiamazole. PATIENTS
      AND METHODS: Studies were carried out in 20 women with newly diagnosed
      hyperthyroidism in the course of Graves-Basedow disease and in 15 healthy women.
      Measurements of activity of antioxidant enzymes--superoxide dismutase (cytosolic
      copper/zinc isoform--Cu/ZnSOD, mitochondrial manganese isoform--MnSOD and
      extracellular copper/zinc isoform--EC-SOD) and glutathione peroxidase (GPx), as
      well as of malondialdehyde (MDA) concentration were performed twice, i.e. before
      the treatment and after 3-7 months of thiamazole therapy (euthyroidism). RESULTS:
      Before the treatment, higher MnSOD plasma activity and lower EC-SOD activity were
      observed in women with hyperthyroidism in comparison with the control group,
      whereas the erythrocyte Cu/ZnSOD activity did not differ between the groups.
      Besides, women with hyperthyroidism had higher GPx activity in red blood cells.
      In this group studies have demonstrated higher plasma MDA levels, without any
      differences between the groups in MDA levels in red blood cells. After thiamazole
      therapy no differences could be demonstrated in MnSOD, EC-SOD, Cu/ZnSOD and GPx
      activities and MDA level between the groups. CONCLUSIONS: Women with
      hyperthyroidism in the course of Graves-Basedow disease experience abnormal
      oxidative status of the organism, and induction of euthyroidism after therapy
      with thiamazole results in resolution of these abnormalities.

PMID- 18714738
TI  - Clinical aspects of Helicobacter pylori infection.
AB  - The Helicobacter pylori (Hp) infection is common. However, only 10-20% of
      infected individuals require antibacterial treatment. The main indications to
      such treatment are peptic ulcer disease, atrophic gastritis, dyspeptic symptoms,
      previous surgical procedure for gastric cancer, family history of gastric cancer
      and low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The
      treatment may also be undertaken at the patient's request. To detect the
      infection the urease test (when the patient has indications for gastroscopy), the
      urea breath test or serologic test are most commonly used. A standard treatment
      of Hp infection consists of a 7-day administration of one of the proton pump
      inhibitors and 2 out of 3 antibiotics such as amoxicillin, clarithromycin and
      metronidazole. After failure of the first-line treatment, the recommended second
      choice treatment is a quadruple treatment regimen consisting of bismuth salts,
      tetracycline, metronidazole and proton pump inhibitor. European guidelines
      (Maastricht III) allow the use of the quadruple treatment regimen already as the
      first choice treatment and therapy prolongation up to 14 days. Ineffectiveness of
      the second-line treatment is an indication for antimicrobial susceptibility
      testing. New antibiotics used for Hp eradication are levofloxacin and rifabutin.
      Eradication treatment should be obligatorily assessed with the use of the urease
      or breath test only in patients with peptic ulcer bleeding. The current
      guidelines do not envisage an active search for Hp infection in an asymptomatic
      population and treating people infected with this bacterium, for gastric cancer
      prevention.

PMID- 18714739
TI  - Drug-induced abnormalities of potassium metabolism.
AB  - Pharmacotherapy has progressed rapidly over the last 20 years with the result
      that general practioners more and more often use drugs which may influence
      potassium metabolism at the kidney or gastrointestinal level, or the
      transmembrane transport of potassium at the cellular level. Potassium
      abnormalities may result in life-theatening clinical conditions. Hypokalemia is
      most frequently caused by renal loss of this electrolyte (thiazide, thiazide-like
      and loop diuretics, glucocorticoids) and the gastrointestinal tract (laxatives,
      diarrhea, vomiting, external fistula), and may be the result of an increased
      intracellular potassium influx induced by sympathicomimetics used mostly by
      patients with asthma, or by insulin overdosage in diabetic subjects. The leading
      symptoms of hypokalemia are skeletal and smooth muscle weakness and cardiac
      arrhythmias. Hyperkalemia may be caused by acute or end-stage renal failure,
      impaired tubular excretion of potassium (blockers of the renin-angiotensin
      aldosterone system, nonsteroidal anti-inflammatory drugs, cyclosporine,
      antifungal drugs, potassium sparing diuretics), acidemia, and severe cellular
      injury (tumor lysis syndrome). Hyperkalemia may be the cause of severe injury of
      both skeletal and smooth muscle cells. The specific treatment counteracting
      hyperkalemia is a bolus injection of calcium salts and, when necessary,
      hemodialysis.

PMID- 18714740
TI  - Problems in differential diagnosis of diabetes types.
AB  - Diabetes mellitus is a group of diseases characterized by chronic increase of
      glucose level. The last years brought progress in understanding the multiplicity
      of its forms, as well as, its complex pathogenesis. In 1999, a classification of
      diabetes based on the etiology of individual types, was proposed by the Experts
      Committee of the World Health Organization, and is now commonly accepted.
      Etiologic classification in the last decade was gradually extended with the
      progress of knowledge, in particular, with successes of researchers in the field
      of genetics. Monogenic forms of diabetes such as MODY, mitochondrial diabetes,
      neonatal diabetes and lipoatrophic diabetes, discovered over a dozen years ago,
      are characterized by unique clinical features and possibility of applying a
      tailored treatment, assuring optimal correction of genetically conditioned
      metabolic defect. The differential diagnostics of types of the diseases is
      playing an increasing role in diabetology, as it enables selection of optimal
      treatment methods, as well as, the assessment of prognosis referring to the
      diabetes course and complications occurence. In this article, a review of
      problems associated with the differential diagnostics of diabetes and its
      practical clinical application was made.

PMID- 18714741
TI  - Does early intervention with inhaled corticosteroids alter the natural history of
      mild persistent asthma?
AB  - In most patients, both adults and children, who have a new diagnosis of asthma
      and whose symptoms are mild but persistent, treatment with inhaled
      corticosteroids (ICS) should be recommended as soon as the diagnosis is made.
      This is a cost-effective and safe treatment. Patients should be cautioned that
      their asthma will not be cured with short-term treatment and that their symptoms
      may recur and their lung function may decline again if treatment is discontinued.
      If patients are reluctant to use ICS daily for long periods of time, it would be
      reasonable to delay the onset of treatment with ICS. They could subsequently be
      managed with intermittent therapy with either ICS or in combination with other
      medications, such as long-acting beta-agonists. Initial therapy with leukotriene
      receptor antagonist is not likely to be as effective as initial therapy with ICS.
      Since treatment adjustments based on eosinophil counts in sputum can reliably
      predict short-term responses to corticosteroids and help identify the appropriate
      add-on therapy, it may be useful to use this measurement, when available, to
      guide intermittent therapy.

PMID- 18714742
TI  - Hemostasis abnormalities in liver cirrhosis: myth or reality?
AB  - Chronic liver disease is characterized by a global hemostatic defect that
      includes platelet-vessel wall interaction (primary hemostasis), fibrinolysis and
      coagulation causing abnormalities of the relevant laboratory tests. The causal
      relationship between abnormal tests and bleeding has been widely accepted,
      despite the fact that abnormal tests are poorly associated with bleeding. Recent
      evidence from the literature disputes the above paradigm and open new directions
      for laboratory and clinical research in this field.

PMID- 18714743
TI  - Mycoplasma pneumoniae-induced pneumonia with Stevens-Johnson syndrome of acute
      atypical course.
AB  - We present a case of Stevens-Johnson syndrome of acute clinical course with
      massive occupation of the mucus membranes of the respiratory system, oral cavity,
      genitals and conjunctiva in a patient with pneumonia. A probable etiological
      factor was infection with Mycoplasma pneumoniae, however clarithromycin could be
      another potential inducing factor.

PMID- 18714744
TI  - Strategies for success: A PDSA analysis of three QI initiatives in critical care.
AB  - BACKGROUND: Implementation of evidence-based quality improvement (QI) initiatives
      is not without its challenges. Recent experience in the design, implementation,
      and evaluation of three QI initiatives at the University of California, San
      Francisco Medical Center (UCSF) suggests lessons learned that may be
      generalizable to other QI initiatives. INITIATIVES: Between December 2002 and May
      2006, a ventilator bundle of care and a tight glycemic control (TGC) protocol
      were implemented in the intensive care units (ICUs), and early goal-directed
      therapy (EGDT) for patients with severe sepsis or septic shock was implemented in
      the ICUs and emergency department. The initiatives were selected on the basis of
      the magnitude of the problem, strength of the evidence regarding associated
      reductions in morbidity and mortality in the critically ill, and cost
      effectiveness. LESSONS LEARNED: A number of challenges in QI processes and
      strategies for success were identified via retrospective analysis within the
      construct of the Plan-Do-Study-Act model, representing a novel use of the model.
      Pitfalls most commonly occurred in the planning stage. Suggested strategies for
      success include using an interdisciplinary team, selecting a champion, securing
      additional resources, identifying specific goals and providing feedback on
      progress, using work-flow analyses and stepwise implementation and/or pilot
      testing, creating standard work, eliciting feedback from staff, and celebrating
      successes. The knowledge gained from these initiatives has been disseminated at
      UCSF, and the initiatives have helped to raise general awareness regarding the
      importance of quality. CONCLUSIONS: The ventilator bundle of care, TGC, and EGDT
      are still in use at UCSF, with modification of the initiatives occurring as new
      evidence becomes available.

PMID- 18714745
TI  - Clinical microsystems, part 2. Learning from micro practices about providing
      patients the care they want and need.
AB  - BACKGROUND: Usual medical care in the United States is frequently not a
      satisfying experience for either patients or primary care physicians. Whether
      primary care can be saved and its quality improved is a subject of national
      concern. An increasing number of physicians are using microsystem principles to
      radically redesign their practices. Small, independent practices-micro practices
      are often able to incorporate into a few people the frontline attributes of
      successful microsystems such as clear leadership, patient focus, process
      improvement, performance patterns, and information technology. PATIENT FOCUS,
      PROCESS IMPROVEMENT, AND PERFORMANCE PATTERNS: An exemplary microsystem will (1)
      have as its primary purpose a focus on the patient-a commitment to meet all
      patient needs; (2) make fundamental to its work the study, measurement, and
      improvement ofcare-a commitment to process improvement; and (3) routinely measure
      its patterns of performance, "feed back" the data, and make changes based on the
      data. LESSONS FROM MICRO PRACTICES: The literature and experience with micro
      practices suggest that they (1) constitute an important group in which to
      demonstrate the value of microsystem thinking; (2) can become very effective
      clinical microsystems; (3) can reduce their overhead costs to half that of larger
      freestanding practices, enabling them to spend more time working with their
      patients; (4) can develop new tools and approaches without going through layers
      of clearance; and (5) need not reinvent the wheel. CONCLUSIONS: Patient-reported
      data demonstrate how micro practices are using patient focus, process
      improvement, performance patterns, and information technology to improve
      performance. Pati ents should be able to report that they receive "exactly the
      care they want and need exactly when and how they want and need it."

PMID- 18714746
TI  - Teaching residents about practice-based learning and improvement.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education has endorsed
      practice-based learning and improvement (PBLI) as a core competency for
      residents. Health professions educators have sought since the early 1990s to
      incorporate quality improvement principles, methods, and skills into training
      programs. A literature review indicates that questions remain regarding how to
      best train physicians to lead the improvement of patient care. The efficacy of
      two PBLI educational interventions was examined by comparing the performance of
      participating residents with that of controls. INTERVENTIONS: Personal
      improvement projects (PIPs) and a workshop were implemented to teach PBLI to
      internal medicine residents. Residents in an ambulatory block rotation were
      required to complete a PIP. All residents were invited to attend the workshop.
      Those participating in neither served as controls. EVALUATION: An instrument was
      used to assess applied improvement knowledge for PIP participants at project
      completion and all residents six to eight months later. Analysis of variance
      showed no difference between the performance of PIP participants at project
      completion and PIP participants and controls six to eight months later. A second
      analysis compared six- to eight-month follow-up data for residents doing PIP
      only, workshop only, both PIP and workshop, and controls. No significant
      differences were detected among groups. Interrater reliability for the tool was
      good. DISCUSSION: No difference was found between intervention residents and
      controls in the assessment of their ability to apply improvement knowledge. This
      suggests that workshops and PIPs alone will not lead to competence in PBLI.
      Building this competency likely will require more emphasis on experiential
      learning and resident participation in health care improvement projects.

PMID- 18714747
TI  - Deficits in discharge documentation in patients transferred to rehabilitation
      facilities on anticoagulation: results of a systemwide evaluation.
AB  - BACKGROUND: Anticoagulation is a commonly prescribed and effective therapy for
      several medical conditions but requires detailed communication among clinicians
      to avoid adverse patient outcomes following hospital discharge. METHODS:
      Discharge documentation packets of a sample of patients discharged from all five
      acute care hospitals of the Partners Healthcare System to 30 subacute facilities
      in Boston and prescribed anticoagulation for treatment or prophylaxis of
      thromboembolic disease were evaluated. Required data elements included
      information on anticoagulation indication, duration, dosing, monitoring, and
      follow-up. Discharge documentation packets were randomly selected for reviewers
      at acute sites, whereas reviewers at subacute sites selected which packets to
      review. RESULTS: Of 757 patients prescribed anticoagulation at discharge from
      March 2005 through June 2007, duration of therapy (for unfractionated or low
      molecular-weight heparin [UFH/LMWH]) and recent dosing and monitoring information
      (for warfarin) were the areas with the biggest deficits. Of the patients
      prescribed UFH/LMWH or warfarin, 45.4% and 16.4%, respectively, had all the
      required information in the discharge summary. Patients discharged from community
      hospitals were more likely to be discharged with all the information needed for
      the use of warfarin (Odds Ratio [OR], 2.56; 95% confidence interval [CI], 1.20
      5.46) or UFH/LMWH (OR, 2.97; 95% CI, 1.98-4.44) than patients discharged from
      academic medical centers. DISCUSSION: Important information to safely prescribe
      anticoagulation after discharge was often missing from the discharge summaries of
      patients transferred from acute hospitals to subacute facilities. Future research
      should focus on developing, implementing, and evaluating quality improvement
      interventions to address this gap.

PMID- 18714748
TI  - A survey of the impact of disruptive behaviors and communication defects on
      patient safety.
AB  - BACKGROUND: A recent survey was conducted to assess the significance of
      disruptive behaviors and their effect on communication and collaboration and
      impact on patient care. SURVEY: VHA West Coast administered a 22-question survey
      instrument--Nurse-Physician: Impact of Disruptive Behavior on Patient Care--to a
      convenience sample. Of the 388 member hospitals (in four VHA regions) invited,
      102 hospitals participated in the survey (26% response rate). Results from
      surveys received from January 2004 though March 2007 are represented. Of the
      4,530 participants, 2,846 listed their titles as nurses, 944 as physicians, 40 as
      administrative executives, and 700 as "other." RESULTS: A total of 77% of the
      respondents reported that they had witnessed disruptive behavior in physicians-
      88% of the nurses and 51% of the physicians. Sixty-five percent of the
      respondents reported witnessing disruptive behavior in nurses at their hospitals-
      73% of the nurses and 48% of the physicians. Sixty-seven percent of the
      respondents agreed that disruptive behaviors were linked with adverse events; the
      result for medical errors was 71%, and patient mortality, 27%. DISCUSSION: The
      results from the survey show that disruptive behaviors lead to potentially
      preventable adverse events, errors, compromises in safety and quality, and
      patient mortality. Strategies to address disruptive behaviors should (1) prevent
      disruptive events from occurring, (2) deal with events in real time to prevent
      staff or patient harm, and (3) initiate postevent review, actions, and follow-up.
      RECOMMENDATIONS: Twelve recommendations--including recognition and awareness,
      policies and procedures, incident reporting, education and training,
      communication tools, discussion forums, and intervention strategies--address what
      hospitals and other organizations can do now to address disruptive behaviors.

PMID- 18714749
TI  - Suicide in inpatient settings: are our hospitals safe enough?
AB  - The authors discuss the implications of findings regarding suicides in hospitals.

PMID- 18714750
TI  - Suicide in the medical setting.
AB  - BACKGROUND: Little is known about suicide in the hospital setting. Although
      suicide is a major public health concern, the literature on suicide in the
      medical setting is limited, and accurate data on hospital-based suicides are
      unavailable. Consequently, the prevalence, demographic characteristics, and risk
      factors for suicide in this population are unknown. The literature on completed
      suicides in medical or surgical wards of a general hospital was summarized to
      generate hypotheses for further investigation regarding in-hospital suicides.
      METHODS: MEDLINE, PsycINFO, IndexCat, and Scopus were queried for English
      language articles on inpatient suicides in a general hospital. These data were
      compared with reports of suicide by psychiatric inpatients and the annual suicide
      statistics from the U.S. general population. RESULTS: Twelve articles detailing
      335 suicides in the medical setting were included. Published data on hospital
      based suicides are limited by selection bias, incomplete reporting, and a small
      number of completed suicides. Consequently, no significant setting-specific
      findings emerge from the existing literature. Reported cases suggest that
      inpatients who commit suicide in the medical setting may have a different
      demographic profile and employ different methods of suicide in comparison with
      individuals who commit suicide in psychiatric settings or the general population.
      DISCUSSION: Given the absence of systematic data collection and the highly
      variable nature of reported suicides, it could not be determined if clinically
      relevant distinctions exist between suicides in different health care settings.
      Prospective and more detailed data collection are needed because a more complete
      characterization of suicide in medical inpatients may be useful in both
      prevention approaches and institutional policies with respect to hospital-based
      suicides.

PMID- 18714751
TI  - Inpatient suicide and suicide attempts in Veterans Affairs hospitals.
AB  - BACKGROUND: Suicide is the eleventh leading cause of death in the United States.
      Approximately 1,500 suicides occur in inpatient hospital units in the United
      States each year. In an attempt to determine the methods and environmental
      factors involved in inpatient suicide and suicide attempts in Department of
      Veterans Affairs (VA) hospitals, all root cause analysis (RCA) reports of
      inpatient suicides and suicide attempts submitted to the VA National Center for
      Patient Safety (NCPS) before June 2006 were reviewed. METHODS: VA medical centers
      are required to conduct RCAs on all inpatient suicides and report all suicides
      and serious suicide attempts to the NCPS. All reports of inpatient suicide and
      suicide attempts submitted between December 1999 and June 2006 were reviewed,
      including methods and environmental factors involved in the events. RESULTS: A
      total of 185 inpatient suicide and suicide attempts were reported; 42 were
      completed suicides and 143 were suicide attempts. Approximately 52% of the total
      number of events occurred while the patient was on an inpatient psychiatry unit.
      Three methods of self harm--intentional drug overdose, cutting with a sharp
      object, and hanging--accounted for 71% of the total number of events. Doors and
      wardrobe cabinets accounted for 41% of the anchor points when hanging was the
      method of self-harm. For suicide attempts involving cutting behaviors, razor
      blades accounted for 37% of the total number of events; 57% of jumping-related
      events occurred from balconies and walkways. CONCLUSIONS: Careful review of RCA
      reports of inpatient suicide has resulted in focused interventions to improve
      patient care and patient safety in VA medical centers, including a comprehensive
      environment-of-care checklist for reviewing inpatient psychiatry units.

PMID- 18714752
TI  - The growth of rapid response systems.
AB  - This conference report presents highlights from the recent Fourth International
      Conference on Rapid Response Systems (RRSs) and Medical Emergency Teams.

PMID- 18714754
TI  - Labor law.

PMID- 18714755
TI  - MAC attack.

PMID- 18714756
TI  - Advanced imaging programs: maximizing a multislice CT investment.
AB  - Advanced image processing has moved from a luxury to a necessity in the practice
      of medicine. A hospital's adoption of sophisticated 3D imaging entails several
      important steps with many factors to consider in order to be successful. Like any
      new hospital program, 3D post-processing should be introduced through a strategic
      planning process that includes administrators, physicians, and technologists to
      design, implement, and market a program that is scalable-one that minimizes up
      front costs while providing top level service. This article outlines the steps
      for planning, implementation, and growth of an advanced imaging program.

PMID- 18714757
TI  - IT and me.

PMID- 18714758
TI  - Mala praxis: a study of malpractice claims and litigation in the field of
      radiology.
AB  - Risk management plays an integral role in the mitigation of malpractice claims in
      the radiology environment. This holds true for the radiologist and professional
      association as well as the facility that supports the radiologic service. The
      radiologist and the radiology department or imaging center are separate entities
      which have a symbiotic relationship. Radiologists may function as an independent
      contractor, yet their function is dependent on the facility with which it
      contracts. The function of the radiology department is directly related to the
      radiologist's performance, staff competency, and equipment performance.
      Mammography poses particular concern with regard to medical malpractice, as there
      is an inherent subjectivity in the differential diagnosis with regard to breast
      cancer in mammography.

PMID- 18714759
TI  - Image center management: what everyone assumes you know.

PMID- 18714760
TI  - Motivation in a multigenerational radiologic science workplace.
AB  - For the first time in history, radiologic science (RS) workplaces consist of 4
      generational cohorts. As each cohort possess their own attitudes, values, work
      habits, and expectations, motivating a generational diverse workplace is
      challenging. Through the understanding of generational differences, managers are
      better able to accommodate individual as well as generational needs and help
      create a more productive and higher performing workplace. The purpose of this
      paper is to assist managers in the understanding and utilization of generational
      differences to effectively motivate staff in an RS workplace. Generational
      cohorts will be defined and discussed along with an in-depth discussion on each
      of the generations performing in today's RS workplace. Motivators and how they
      impact the different generational cohorts will be addressed along with how to
      best motivate a multigenerational RS workplace.

PMID- 18714761
TI  - Too young to retire, but can an old dog learn new tricks?

PMID- 18714762
TI  - Cost containment, CT scanning, and the future of healthcare technologies. 1978.

PMID- 18714763
TI  - Current ratio and quick ratio (acid) tests.

PMID- 18714764
TI  - I'm not your momma.

PMID- 18714765
TI  - What's your diagnosis? Cervical spine trauma: unstable fractures, C2-C7 injuries,
      and imaging guidelines.

PMID- 18714766
TI  - Is extent of laminectomy important in shortening procedures?

PMID- 18714767
TI  - Orthopedic residency training in Germany: an endangered species?

PMID- 18714768
TI  - Long-term functional outcomes after intra-articular distal femur fractures: ORIF
      versus retrograde intramedullary nailing.
AB  - This retrospective study evaluated the long-term clinical, functional, and
      radiographic outcomes of traditional open reduction internal fixation (ORIF)
      versus limited open reduction with retrograde intramedullary nailing for
      supracondylar-intercondylar distal femur fractures (Arbeitsgemeinschaft fur
      Osteosynthesefragen [AO] 33-C type). Twenty-three fractures were followed in 22
      patients for a mean follow-up of 80 months. The rate of subsequent bone-grafting
      procedures (67% vs 9%) and malunion (42% vs 0%) were significantly higher in ORIF
      compared to the less invasive retrograde intramedullary nailing treatment. A
      nonsignificant trend was noted for increased infection (25% vs 0%) and nonunion
      (33% vs 9%) in the ORIF group. The physical function component of the SF-36 was
      approximately 2 standard deviations below the US population mean, and 50% of
      patients demonstrated radiographic changes of posttraumatic arthritis. No patient
      has had a subsequent total knee arthroplasty.

PMID- 18714769
TI  - An alternative direction for proximal locking in retrograde femoral nails.
AB  - Lateral-to-medial proximal interlocking screw insertion for retrograde femoral
      nails avoids potential neurovascular injury while maintaining stable interlocking
      mechanics.

PMID- 18714770
TI  - Detecting vascular injury in lower-extremity orthopedic trauma: the role of CT
      angiography.
AB  - As a screening tool, CT angiography has excellent sensitivity and specificity
      combined with fewer complications compared to conventional arteriography.

PMID- 18714771
TI  - Risk factors, prevention, and treatment of corticosteroid-induced osteoporosis in
      adults.
AB  - An orthopedist can play a critical role in corticosteroid induced osteoporosis
      management by identifying at-risk patients and selecting appropriate prophylactic
      measures. This article is part two in a two-part series on osteoporosis. Part one
      appeared in the July 2008 issue of ORTHOPEDICS.

PMID- 18714772
TI  - Humeral avulsion of the glenohumeral ligament: injury pattern and arthroscopic
      repair techniques.
AB  - The arthroscopic treatment of a humeral avulsion of the glenohumeral ligaments
      lesion allows for a safe, reproducible, and effective way to reestablish the
      inferior glenohumeral ligament and capsular complex to the humerus.

PMID- 18714773
TI  - Morbidity and mortality of simultaneous bilateral total knee arthroplasty.

PMID- 18714774
TI  - The unstable intertrochanteric hip fracture.
AB  - An unstable intertrochanteric fracture of the hip is a fracture that has the
      potential to displace or result in nonunion despite what appears to be adequate
      reduction and internal fixation. One cause of instability, namely marked
      displacement at the fracture site, is identified here and should now be included
      among the risk factors. Early identification of the instability is imperative.
      Treatment options are modification of reduction techniques, choices of internal
      fixation devices, and adjustment of postoperative care. The importance of
      adjusting the treatment to the requirements of an unstable intertrochanteric
      fracture is emphasized.

PMID- 18714775
TI  - Traumatic rupture of the latissimus dorsi.

PMID- 18714776
TI  - Does untreated obstructive sleep apnea lead to death? A commentary on Young et
      al. Sleep 2008;31:1071-8 and Marshall et al. Sleep 2008;31:1079-85.

PMID- 18714777
TI  - Response to restless legs syndrome and diabetic neuropathy--commentary by
      Gemignani, et al.

PMID- 18714778
TI  - Sleep disordered breathing and mortality: eighteen-year follow-up of the
      Wisconsin sleep cohort.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) is a treatable but markedly under
      diagnosed condition of frequent breathing pauses during sleep. SDB is linked to
      incident cardiovascular disease, stroke, and other morbidity. However, the risk
      of mortality with untreated SDB, determined by polysomnography screening, in the
      general population has not been established. METHODS: An 18-year mortality follow
      up was conducted on the population-based Wisconsin Sleep Cohort sample (n =
      1522), assessed at baseline for SDB with polysomnography, the clinical diagnostic
      standard. SDB was described by the number of apnea and hypopnea episodes/hour of
      sleep; cutpoints at 5, 15 and 30 identified mild, moderate, and severe SDB,
      respectively. Cox proportional hazards regression was used to estimate all-cause
      and cardiovascular mortality risks, adjusted for potential confounding factors,
      associated with SDB severity levels. RESULTS: All-cause mortality risk, adjusted
      for age, sex, BMI, and other factors was significantly increased with SDB
      severity. The adjusted hazard ratio (HR, 95% CI) for all-cause mortality with
      severe versus no SDB was 3.0 (1.4,6.3). After excluding persons who had used CPAP
      treatment (n = 126), the adjusted HR (95% CI) for all-cause mortality with severe
      versus no SDB was 3.8 (1.6,9.0); the adjusted HR (95% CI) for cardiovascular
      mortality was 5.2 (1.4,19.2). Results were unchanged after accounting for daytime
      sleepiness. CONCLUSIONS: Our findings of a significant, high mortality risk with
      untreated SDB, independent of age, sex, and BMI underscore the need for
      heightened clinical recognition and treatment of SDB, indicated by frequent
      episodes of apnea and hypopnea, irrespective of symptoms of sleepiness.

PMID- 18714779
TI  - Sleep apnea as an independent risk factor for all-cause mortality: the Busselton
      Health Study.
AB  - BACKGROUND: Previously published cohort studies in clinical populations have
      suggested that obstructive sleep apnea (OSA) is a risk factor for mortality
      associated with cardiovascular disease. However, it is unknown whether sleep
      apnea is an independent risk factor for all-cause mortality in a community-based
      sample free from clinical referral bias. METHODS: Residents of the Western
      Australian town of Busselton underwent investigation with a home sleep apnea
      monitoring device (MESAM IV). OSA was quantified via the respiratory disturbance
      index (RDI). Mortality status was determined in 397/400 participants (99.3%)
      after up to 14 years (mean follow-up 13.4 years) by data matching with the
      Australian National Death Index and the Western Australian Death Register.
      Univariate analyses and multivariate Cox proportional hazards modelling were used
      to ascertain the association between sleep apnea and mortality after adjustment
      for age, gender, body mass index, mean arterial pressure, total cholesterol, high
      density lipoprotein cholesterol, diabetes, and medically diagnosed angina in
      those free from heart attack or stroke at baseline (n = 380). RESULTS: Among the
      380 participants, 18 had moderate-severe OSA (RDI > or = 15/hr, 6 deaths) and 77
      had mild OSA(RDI 5 to < 15/hr, 5 deaths). Moderate-to-severe OSA was
      independently associated with greater risk of all-cause mortality (fully adjusted
      hazard ratio [HR] = 6.24, 95% CL 2.01, 19.39) than non-OSA (n = 285, 22 deaths).
      Mild OSA (RDI 5 to < 15/hr) was not an independent risk factor for higher
      mortality (HR = 0.47, 95% CL 0.17, 1.29). CONCLUSIONS: Moderate-to-severe sleep
      apnea is independently associated with a large increased risk of all-cause
      mortality in this community-based sample.

PMID- 18714780
TI  - Sleep duration associated with mortality in elderly, but not middle-aged, adults
      in a large US sample.
AB  - STUDY OBJECTIVES: To explore age differences in the relationship between sleep
      duration and mortality by conducting analyses stratified by age. Both short and
      long sleep durations have been found to be associated with mortality. Short sleep
      duration is associated with negative health outcomes, but there is little
      evidence that long sleep duration has adverse health effects. No epidemiologic
      studies have published multivariate analyses stratified by age, even though life
      expectancy is 75 years and the majority of deaths occur in the elderly. DESIGN:
      Multivariate longitudinal analyses of the first National Health and Nutrition
      Examination Survey using Cox proportional hazards models. SETTING: Probability
      sample (n = 9789) of the civilian noninstitutionalized population of the United
      States between 1982 and 1992. PARTICIPANTS: Subjects aged 32 to 86 years.
      MEASUREMENTS AND RESULTS: In multivariate analyses controlling for many
      covariates, no relationship was found in middle-aged subjects between short sleep
      of 5 hours or less and mortality (hazards ratio [HR] = 0.67, 95% confidence
      interval [CI] 0.43-1.05) or long sleep of 9 hours or more and mortality (HR =
      1.04, 95% CI 0.66-1.65). A U-shaped relationship was found only in elderly
      subjects, with both short sleep duration (HR = 1.27, 95% CI 1.06-1.53) and long
      sleep duration (HR = 1.36, 95% CI 1.15-1.60) having significantly higher HRs.
      CONCLUSIONS: The relationship between sleep duration and mortality is largely
      influenced by deaths in elderly subjects and by the measurement of sleep
      durations closely before death. Long sleep duration is unlikely to contribute
      toward mortality but, rather, is a consequence of medical conditions and age
      related sleep changes.

PMID- 18714781
TI  - Association between short sleep and suicidal ideation and suicide attempt among
      adults in the general population.
AB  - OBJECTIVE: To determine the association between sleep, mental disorders, and
      suicidal ideation (SI) and suicide attempt (SA) among adults in the community.
      DESIGN: Cross-sectional. SETTING: National Comorbidity Survey (n = 8098).
      PARTICIPANTS: A representative sample of adults in the United States.
      MEASUREMENTS AND RESULTS: Multiple logistic regression analyses were used to
      determine the association between usual number of hours of sleep during a 24-h
      period and SI and SA (past 12 months and lifetime). Analyses were adjusted for
      differences in demographic characteristics and comorbid mental disorders.
      Additional analyses examined the relationship between hours of sleep and the odds
      of SA among adults with SI, compared with SI without SA. Short sleep was
      associated with significantly increased odds of SI (OR 2.5, 95% CI: 1.6-3.9) and
      SA (OR 3.0, 95% CI: 1.4-6.4), and with SA among those with SI (past 12 months).
      These associations persisted after adjusting for differences in demographic
      characteristics and mental disorders, though the links between short sleep and SA
      among those with SI were no longer statistically significant after adjusting for
      panic, mood, and substance use disorders. CONCLUSIONS: Short sleep appears to be
      associated with increased likelihood of SI and SA, independent of the effects of
      comorbid mental disorders, among adults in the community. Among adults with SI,
      short sleep is associated with increased odds of SA, and this association seems
      largely related to the presence of panic attacks, mood, and substance use
      disorders. Future studies should investigate the nature of these relationships,
      and whether and how mental health problems may play a role.

PMID- 18714782
TI  - Neural alterations and depressive symptoms in obstructive sleep apnea patients.
AB  - STUDY OBJECTIVES: Depressive symptoms are common in obstructive sleep apnea (OSA)
      patients, and brain injury occurs with both OSA and depression independently. The
      objective was to determine whether brain alterations in OSA bear relationships to
      depressive symptoms. DESIGN: Cross-sectional study. SETTING: University-based
      medical center. PARTICIPANTS: 40 treatment-naive OSA subjects and 61 control
      subjects without diagnosed psychopathology. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: Whole-brain maps of T2 relaxation time, a measure sensitive to injury,
      were calculated from magnetic resonance images, transformed to common space, and
      smoothed. Control and OSA groups were classified by Beck Depression Inventory
      (BDI)-II scores (> or =12 symptomatic, <10 asymptomatic for depressive symptoms).
      The OSA group separated into 13 symptomatic (mean +/- SD: BDI-II 21 +/- 8; age
      47.6 +/- 11; apnea hypopnea index [AHI] 28.3 +/- 17), and 27 asymptomatic (4 +/-
      3; 47.5 +/- 8; 31.5 +/- 16) subjects. The control group included 56 asymptomatic
      (BDI-II 2.5 +/- 2.6; age 47.3 +/- 9) subjects. Asymptomatic OSA subjects
      exhibited higher AHI. T2 maps were compared between groups (ANCOVA), with age and
      gender as covariates. Injury appeared in symptomatic vs asymptomatic OSA subjects
      in the mid- and anterior cingulate, anterior insular, medial pre-frontal,
      parietal, and left ventrolateral temporal cortices, left caudate nucleus, and
      internal capsule. Relative to asymptomatic controls, symptomatic OSA patients
      showed damage in the bilateral hippocampus and caudate nuclei, anterior corpus
      callosum, right anterior thalamus, and medial pons. CONCLUSIONS: Neural injury
      differed between OSA patients with and without depressive symptoms. Depressive
      symptoms may exacerbate injury accompanying OSA, or introduce additional damage
      in affective, cognitive, respiratory, and autonomic control regions.

PMID- 18714783
TI  - Genetic association of daytime sleepiness and depressive symptoms in elderly men.
AB  - STUDY OBJECTIVES: Clinical rating scales, self-reports, and diagnostic
      instruments measuring depression often inquire about daytime fatigue and
      tiredness. Excessive daytime sleepiness refers specifically to the tendency to
      feel drowsy or fall asleep during waking hours and is considered conceptually and
      operationally independent from the fatigue, tiredness, and sleeping difficulties
      that characterize depression. The objective of this study was to examine whether
      daytime sleepiness assessed using the Epworth Sleepiness Scale and depressive
      symptoms assessed using the Geriatric Depression Scale are genetically related.
      DESIGN/SETTING: Cross-sectional data were collected via questionnaire in 1998
      2000. PARTICIPANTS: Population-based sample of more than 5,000 male elderly twins
      aged 69-82 years old at the time of survey. INTERVENTIONS: N/A. MEASUREMENTS AND
      RESULTS: There was evidence for moderate heritability for daytime sleepiness
      (36.9%) and depressive symptoms (30.7%). There was evidence for a significant
      genetic correlation (0.40) between the 2 measures, suggesting that both daytime
      sleepiness and depressive symptoms have some genes in common. The genetic
      correlation was reduced to 0.21 after adjustment for several covariates.
      CONCLUSIONS: The results showed that the often reported phenotypic correlation
      between daytime sleepiness and depressive symptoms is due, in part, to modest
      overlap in genetic factors, at least in elderly men. However, the majority of
      individual variation in daytime sleepiness and depressive symptoms, in particular
      after covariate adjustment, was attributable to individual-specific environmental
      factors.

PMID- 18714784
TI  - Hypocretin receptor expression in canine and murine narcolepsy models and in
      hypocretin-ligand deficient human narcolepsy.
AB  - STUDY OBJECTIVE: To determine whether hypocretin receptor gene (hcrtR1 and
      hcrtR2) expression is affected after long-term hypocretin ligand loss in humans
      and animal models of narcolepsy. DESIGN: Animal and human study. We measured
      hcrtR1 and hcrtR2 expression in the frontal cortex and pons using the RT-PCR
      method in murine models (8-week-old and 27-week-old orexin/ataxin-3 transgenic
      (TG) hypocretin cell ablated mice and wild-type mice from the same litter, 10
      mice for each group), in canine models (8 genetically narcoleptic Dobermans with
      null mutations in the hcrtR2, 9 control Dobermans, 3 sporadic ligand-deficient
      narcoleptics, and 4 small breed controls), and in humans (5 narcolepsy-cataplexy
      patients with hypocretin deficiency (average age 77.0 years) and 5 control
      subjects (72.6 years). MEASUREMENT AND RESULTS: 27-week-old (but not 8-week-old)
      TG mice showed significant decreases in hcrtR1 expression, suggesting the
      influence of the long-term ligand loss on the receptor expression. Both sporadic
      narcoleptic dogs and human narcolepsy-cataplexy subjects showed a significant
      decrease in hcrtR1 expression, while declines in hcrtR2 expression were not
      significant in these cases. HcrtR2-mutated narcoleptic Dobermans (with normal
      ligand production) showed no alteration in hcrtR1 expression. CONCLUSIONS:
      Moderate declines in hcrtR expressions, possibly due to long-term postnatal loss
      of ligand production, were observed in hypocretin-ligand deficient narcoleptic
      subjects. These declines are not likely to be progressive and complete. The
      relative preservation of hcrtR2 expression also suggests that hypocretin based
      therapies are likely to be a viable therapeutic options in human narcolepsy
      cataplexy.

PMID- 18714785
TI  - Sleep disordered breathing and hypertension: does self-reported sleepiness modify
      the association?
AB  - STUDY OBJECTIVES: Epidemiologic studies that demonstrate increased risk of
      hypertension in persons with sleep disordered breathing indicate that only a
      minority of these persons report significant subjective sleepiness. Studies also
      suggest that presence of self-reported sleepiness may identify a subset of
      persons with sleep disordered breathing who are at greatest risk of
      cardiovascular sequelae, including hypertension. We explore whether self-reported
      sleepiness modifies the relationship between sleep disordered breathing and
      prevalent hypertension. DESIGN: Cross-sectional. SETTING: Multicenter study.
      PARTICIPANTS: 6046 subjects from the Sleep Heart Health Study. MEASUREMENTS:
      Polysomnography, systolic and diastolic blood pressure, antihypertensive
      medication use, questionnaire determined excessive sleepiness and Epworth
      Sleepiness Scale, and covariates. RESULTS: The odds of hypertension at higher
      apnea hypopnea index categories were larger in participants identified as sleepy
      based on responses to a frequency of sleepiness question or the Epworth score.
      For example, for those with AHI > or =30 compared to AHI <1.5, the adjusted odds
      ratio for hypertension was 2.83 (1.33-6.04) among those reporting sleepiness > or
      =5 days per month, but only 1.22 (0.89-1.68) among those reporting less frequent
      daytime sleepiness. In adjusted logistic regression models, there was statistical
      evidence for effect modification by frequency of sleepiness (P = 0.033) of the
      association between apnea hypopnea index and hypertension. In adjusted models
      that included the Epworth score as a continuous variable, the interaction term
      fell slightly short of statistical significance (beta = 0.010, P = 0.07).
      CONCLUSION: This study finds that the association of sleep disordered breathing
      with hypertension is stronger in individuals who report daytime sleepiness than
      in those who do not.

PMID- 18714786
TI  - Prone sleeping impairs circulatory control during sleep in healthy term infants:
      implications for SIDS.
AB  - STUDY OBJECTIVES: To determine the effects of sleeping position on development of
      circulatory control in infants over the first 6 months of postnatal age (PNA).
      DESIGN: Effects of sleeping position, sleep state and PNA on beat-beat heart rate
      (HR) and mean arterial pressure (MAP) responses to a head-up tilt (HUT) were
      assessed during sleep in infants at 2-4 wks, 2-3 mo and 5-6 mo PNA. MEASUREMENTS:
      Daytime polysomnography was performed on 20 full-term infants (12 F/8 M) and MAP
      was recorded continuously and noninvasively (Finometer). HUTs of 15 degrees were
      performed during active sleep (AS) and quiet sleep (QS) in both the prone and
      supine sleeping positions. MAP and HR data were expressed as the percentage
      change from baseline, and responses were divided into initial, middle and late
      phases. RESULTS: In the supine position HUT usually resulted in an initial
      increase (P < 0.05) in HR and MAP, followed by decreases (P < 0.05) in HR and MAP
      in the middle phase; subsequently HR and MAP returned to baseline in the late
      phase. By contrast, in the prone position the initial HUT-induced rises in HR and
      MAP were usually absent, and at 2-3 mo MAP actually decreased (P < 0.05);
      subsequently HR but not MAP returned to baseline. At 2-3 mo, MAP was lower (P <
      0.05) in prone than supine sleeping throughout the HUT. CONCLUSIONS: Prone
      sleeping alters MAP responses to a HUT during QS at 2-3 mo PNA. Decreased
      autonomic responsiveness may contribute to the increased risk for SIDS of infants
      sleeping in the prone position.

PMID- 18714787
TI  - Motor sequence learning increases sleep spindles and fast frequencies in post
      training sleep.
AB  - STUDY OBJECTIVES: To investigate polysomnographic (PSG) sleep and NREM sleep
      characteristics, including sleep spindles and spectral activity involved in
      offline consolidation of a motor sequence learning task. DESIGN: Counterbalanced
      within-subject design. SETTING: Three weekly visits to the sleep laboratory.
      PARTICIPANTS: Fourteen healthy participants aged between 20 and 30 years (8
      women). INTERVENTIONS: Motor sequence learning (MSL) task or motor control (CTRL)
      task before sleep. MEASUREMENTS AND RESULTS: Subjects were trained on either the
      MSL or CTRL task in the evening and retested 12 hours later the following morning
      on the same task after a night of PSG sleep recording. Total number and duration
      of sleep spindles and spectral power between 0.5 and 24 Hz were quantified during
      NREM sleep. After performing the MSL task, subjects exhibited a large increase in
      number and duration of sleep spindles compared to after the CTRL task. Higher
      sigma (sigma; 13 Hz) and beta (beta; 18-20 Hz) spectral power during the post
      training night's sleep were also observed after the MSL task. CONCLUSIONS: These
      results provide evidence that sleep spindles are involved in the offline
      consolidation of a new sequence of finger movements known to be sleep dependent.
      Moreover, they expand on prior findings by showing that changes in NREM sleep
      following motor learning are specific to consolidation (and learning), and not to
      nonspecific motor activity. Finally, these data demonstrate, for the first time,
      higher fast rhythms (beta frequencies) during sleep after motor learning.

PMID- 18714788
TI  - Early morning executive functioning during sleep deprivation is compromised by a
      PERIOD3 polymorphism.
AB  - STUDY OBJECTIVES: To contrast the effects of total sleep deprivation (TSD) on
      executive and non-executive function in volunteers homozygous for either the
      short or long variant of a variable number tandem repeat polymorphism in PERIODS,
      which is a genetic marker for susceptibility to the negative effect of sleep loss
      on waking performance. DESIGN: Following two laboratory nights of baseline sleep,
      both groups underwent an approximately 40-hour constant routine, performing brief
      tests of executive, memory, attention, and motor function every 2 hours. SETTING:
      Clinical Research Centre. PARTICIPANTS: Fourteen PER3(4/4) (homozygotes for
      shorter variant of the gene) and 10 PER3(5/5) (homozygotes for longer variant)
      healthy, young adults (mean 25.0 +/- 1.0 years). INTERVENTIONS: Total sleep
      deprivation (approximately 40 hours) following baseline sleep. MEASUREMENTS AND
      RESULTS: Hormonal assays established that melatonin levels, which reflect
      circadian phase, reached their midpoint around 04:00 in both genotypes. Cognitive
      performance deteriorated across the night, and was similar for both genotypes
      throughout, except 2-4 h after the midpoint of the melatonin rhythm. Only at this
      time-point and only on tests of executive function (e.g., 3-back, paced visual
      serial addition task) did PER3(5/5) participants perform reliably worse.
      Covariance analyses controlling for genotype dependent differences in homeostatic
      sleep pressure derived from principal component analysis of baseline sleep
      latency, slow wave sleep and wake after sleep onset largely removed these early
      morning differences in executive function. CONCLUSIONS: This PER3 polymorphism
      differentially influences the effects of sleep deprivation on executive and non
      executive function in the early morning. These effects appear to be mediated
      through homeostatic sleep pressure.

PMID- 18714789
TI  - Work-related sleep disturbances and sickness absence in the Swedish working
      population, 1993-1999.
AB  - STUDY OBJECTIVES: To examine secular trends in work-related sleep disturbances
      and their association with sickness absence in the Swedish working population.
      DESIGN: Nationally representative cross-sectional samples of the Swedish working
      population aged 16-64 (the biennial Swedish Work Environment Survey) in 1993,
      1995, and 1999 respectively. Questionnaire data on work-related sleep
      disturbances were linked to records of medically-certified sick-leave spells
      exceeding 14 days obtained from national registers. SETTING: All Sweden.
      PARTICIPANTS: A total of 28,424 individuals aged 16-65 with complete data
      (5162/5173 women/men in 1993; 4635/4764 in 1995; and 4422/4268 in 1999).
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The age-adjusted proportion of
      women with work-related sleep disturbances at least once a week increased from
      12.3% in 1993 to 21.7% in 1999 (P < 0.001). The corresponding figures for men
      were 12.5% to 18.6% (P < 0.001). There was a strong cross-sectional association
      between work-related sleep disturbances and sickness absence in both genders and
      in each studied year. Using binary logistic regressions and adjusting for age,
      supervisory position, and geographical region, the odds ratios for sickness
      absence for those who reported work-related sleep disturbances every day,
      compared with those who answered "not at all/seldom last 3 months" varied between
      3.22 (1.88-5.50) and 4.26 (2.56-7.19), with the strongest associations seen in
      1999. Adjustment for health indicators, especially depressive symptoms,
      attenuated the relationship substantially. CONCLUSIONS: Self-reported sleep
      disturbances attributed to work-related causes were on the rise in Sweden and
      were associated with medically-certified sickness absence. Most of this
      association seems to be accounted for by depressive symptoms.

PMID- 18714790
TI  - Diagnosis of REM sleep behavior disorder by video-polysomnographic study: is one
      night enough?
AB  - STUDY OBJECTIVES: Clinical features of RBD were typically episodic with limited
      data on the night-to-night reliability of the diagnostic video-PSGs. We aimed to
      assess on whether a single night study was adequate. DESIGN: Retrospective
      review. SETTING: Sleep laboratory. PARTICIPANTS: 55 RBD patients with at least 2
      consecutive video-PSGs. INTERVENTIONS: N/A. METHODS: We analyzed 2 consecutive
      video-PSGs using REM-related EMG activity (REMREEA), REM sleep without atonia
      (RSWA), and video analysis of motor events. MEASUREMENTS AND RESULTS: A weak
      first night effect with increased REM sleep latency, increased stage 1 sleep, and
      increased arousal index were found. No differences were found in phasic and tonic
      EMG activity scores between night 1 and night 2. The presence of OSAS, use of
      CPAP, and clonazepam treatment did not affect the night-to-night variability and
      diagnostic accuracy. The kappas were 0.64, 0.51, and 0.31 between night 1 and
      night 2 for 10% REMREEA, RSWA, and video analysis respectively. Over 80% of
      patients could be diagnosed by various criteria in the first night, but the
      diagnostic ability could be enhanced to nearly 95% when combining PSG with video
      analysis. While both of the EMG criteria as well as the combination criteria had
      good reliability, video-analysis had poorer night-to-night reliability.
      CONCLUSIONS: A single night of video-PSG was adequate in the diagnosis of RBD in
      most clinical patients and the combination of PSG and video analysis could
      enhance the detection rate further. Our findings have important resource
      implications.

PMID- 18714791
TI  - The return of evidence-based neurology to the journal: it's all about patient
      care.

PMID- 18714792
TI  - VNS therapy.

PMID- 18714793
TI  - Stroke prevention and sodium restriction.

PMID- 18714794
TI  - Seizure freedom reduces illness intrusiveness and improves quality of life in
      epilepsy.
AB  - BACKGROUND: Chronic illnesses are associated with multiple stressors that
      compromise quality of life (QOL). Implicit in many of these stressors is the
      concept of illness intrusiveness: the disruption of lifestyles, activities, and
      interests due to the constraints imposed by chronic disease and its treatment.
      The purpose of this study was to examine illness intrusiveness and QOL in
      epilepsy in patients with different levels of seizure control. METHODS: Cross
      sectional data were obtained and compared between two groups of patients
      categorized by presence of seizures: seizure freedom or continued seizures (N =
      145). Standard instruments measured the following variables: illness
      intrusiveness, perceived personal control, subjective well-being, and disease
      specific QOL. RESULTS: Illness intrusiveness varied inversely and significantly
      with seizure control. Complete seizure freedom, whether achieved by
      pharmacological or surgical treatment, was associated with the lowest levels of
      illness intrusiveness. Seizure freedom was also associated with increased
      perceived control, positive affect, self-esteem and QOL in epilepsy. CONCLUSIONS:
      The most robust benefits of decreased illness intrusiveness in epilepsy occur
      when treatment leads to complete seizure control. Therefore every effort should
      be made by health care providers to achieve seizure freedom to reduce illness
      intrusiveness and improve QOL in epilepsy.

PMID- 18714795
TI  - Quality of life and memory after vagus nerve stimulator implantation for
      epilepsy.
AB  - OBJECTIVE: This prospective, case control study evaluates quality of life (QOL),
      depressive affect, and memory outcomes of epilepsy patients implanted with a
      vagus nerve stimulator (VNS). METHODS: Three groups of patients with epilepsy
      underwent assessment on two occasions: 1) patients with a VNS were tested before
      and 12 months after implantation (n = 16); 2) patients who underwent cerebral
      resective surgery were tested pre- and post-operatively (n = 10); and 3) patients
      under medical management (n = 9). Group means were compared on the QOLIE-89,
      Geriatric Depression Scale, Wechsler Memory Scale - III, and the Memory
      Observation Questionnaire. Secondary analyses calculated the reliable change
      index, providing information on change beyond measurement error and chance.
      RESULTS: Mean ratings of QOL, depression, and memory complaints and objective
      memory scores remained stable or improved in all the groups. The QOL improved
      more after cerebral resective surgery than VNS or medication controls, but the
      VNS and medication control groups did not differ. In the VNS group, QOL was not
      related to seizure reduction. The percentage of cases showing real change in
      memory was equivalent across groups, except in one of eight indices (i.e., verbal
      recognition memory). CONCLUSIONS: This first case controlled design found that
      vagus nerve stimulation as an adjunctive therapy for seizure control did not
      change QOL, depressive affect, or objective memory scores over one-year more so
      than medical management alone. We point out the need for larger case control, non
      industry funded investigations.

PMID- 18714796
TI  - Childhood absence epilepsy requiring more than one medication for seizure
      control.
AB  - INTRODUCTION: Absence epilepsy is the most common primary generalized epilepsy
      syndrome encountered in pediatric practice. Treatment is pharmacologically
      specific and usually successful with a single medication. The objective of this
      study was to identify any clinical or electroencephalographic features at initial
      presentation in a consecutive cohort of children with absence epilepsy that may
      be associated with the need for a second medication. METHODS: A computerized
      pediatric neurology database (1991-2007 inclusive) was retrospectively searched
      for all patients with typical absence seizures, 3 Hz spike and wave on EEG and no
      apparent symptomatic etiology who were over the age of two years at seizure onset
      with at least one year of follow-up. All such children were then divided into two
      groups; a) those requiring a single medication for seizure control (Group 1), and
      b) those requiring two medications for seizure control despite optimal management
      with the initial medication as determined by serum drug monitoring (Group 2).
      Clinical and electrographic features evident at diagnosis were then contrasted
      between Group 1 and 2. RESULTS: Seventy-five children with absence seizures were
      initially identified with 52 meeting the study's inclusion and none of the
      exclusion criteria. Of these 52 children, 43 required a single medication for
      seizure control (Group 1), while 9 required two or more medications for seizure
      control (Group 2). A significant difference (p < 0.05) was apparent between Group
      1 and 2 with respect to gender (16/43 males vs 8/9 males) and mean age of
      diagnosis (8.19 years +/- 3.00 vs 6.06 years +/- 2.22). Age of onset of seizures,
      interval duration of seizures prior to treatment initiation, duration of
      seizures, presence of automatisms, family history, presence of co-morbid
      conditions and EEG findings were not found to be significantly different between
      the two Groups. CONCLUSIONS: Male gender and an earlier age of diagnosis is
      associated with the need for two medications for seizure control in children with
      absence epilepsy. This observation may suggest the need for more intensive early
      programmatic follow-up for young male children with newly diagnosed absence
      epilepsy to effect more rapid attainment of seizure control.

PMID- 18714797
TI  - Sturge-Weber syndrome: study of 55 patients.
AB  - PURPOSE: To review the clinical and neuroimaging features of a large series of
      patients with Sturge-Weber syndrome (SWS) seen over a 40-year period. METHODS:
      Fifty-five patients with SWS (30 males and 25 females), were studied between 1965
      and 2004. Results of neurological and ophthalmological examinations,
      electroencephalographic, and neuroimaging studies were reviewed. All patients
      were seen by one of the authors (I. P-C). RESULTS: Epilepsy, hemiparesis, mental
      retardation and ocular problems were the most frequent and severe features of
      patients with Sturge-Weber syndrome in this series. The facial nevus flammeus was
      unilateral in 35 (63.5%) patients, bilateral in 17 (31%) and absent in 3 (5.5%)
      of the patients with leptomeningeal angiomas. Seven (41%) of the 17 patients with
      bilateral nevus flammeus had unilateral leptomeningeal angiomas. Seizures
      occurred in 47 patients (85.5%). Complete seizure control was obtained in 20
      patients (42.5%), but in 2 of these 20 patients seizures were controlled only
      after lobectomy. All patients with unilateral or bilateral upper eyelid nevus
      flammeus had ipsilateral, unilateral or bilateral choroid-retinal angiomas. Only
      20 (36%) of the 55 patients had low-normal or borderline intelligence (IQs < 70).
      No relationship was observed between the size of the facial nevus flammeus and
      the severity of the brain lesion. CONCLUSIONS: Epilepsy, hemiparesis, mental
      retardation and ocular problems were the most frequent and severe features of
      patients with Sturge-Weber syndrome in this series. Cerebral lesions followed a
      progressive course during early childhood, but not later. Early surgical
      treatment controlled the seizures but other neurological problems such as
      hemiparesis and intellectual deficits showed a less satisfactory response. Early
      onset of seizures and poor response to medical treatment, bilateral cerebral
      involvement and unilateral severe lesions were indicative of a poor prognosis.
      Limited intelligence and social skills, poor aesthetic appearance and seizures
      complicated the integration of SWS patients. These features must be addressed in
      order for the patients improve social interactions, obtain gainful employment and
      achieve a better quality of life.

PMID- 18714798
TI  - Access to spine care: a tale of two cities.
AB  - INTRODUCTION: As governments struggle with increasing demand for accountability
      within the Canadian Health Care System and set wait-time standards, it is
      important to objectify data to allow a true understanding of present limitations
      and to facilitate comparisons to other systems. The purpose of this study was to
      compare wait list times for a cohort of patients requiring spinal surgery in
      Calgary, Alberta to a similar cohort in Sydney, Australia. METHODS: From January
      1 until June 30, 2006 all outpatients admitted for spinal surgery to the
      Foothills Hospital were identified by the surgeons' office. Two time periods were
      quantified from their charts: (1) time from referral to surgical consultation;
      and (2) time from surgical consultation to operative intervention. From July 1
      until December 31,2006 patients were similarly identified through Neurosurgical
      offices at the Prince of Wales Public and Private Hospitals in Sydney, Australia.
      RESULTS: Four hundred ninety-one surgical patients were captured during the six
      month period in Calgary and 155 patients during the subsequent six months in
      Sydney. The majority of patients in Sydney were treated in the Private Health
      Care system. Public patients in Sydney have access to a surgical consultant twice
      as fast as public patients in Calgary while private patients have access ten
      times faster. Access to operating room time within the public system is a rate
      limiting step in both countries. However, Sydney private patients receive their
      surgery four times faster than Calgary patients. CONCLUSIONS: Compared to
      Calgary, access to specialized spine care in Sydney appears more efficient not
      only in the Private but also the Public Health Care System. Part of this
      efficiency may arise from offloading from the public into the private system.
      Solutions proposed to reduce wait list times should consider benefits of a
      Private Health Care System.

PMID- 18714799
TI  - Can clinical data predict progression to dementia in amnestic mild cognitive
      impairment?
AB  - BACKGROUND: To determine whether clinical data obtained by history and physical
      examination can predict eventual progression to dementia in a cohort of elderly
      people with mild cognitive impairment. METHODS: A prospective, longitudinal study
      of a cohort of elderly subjects with amnestic Mild Cognitive Impairment (MCI).
      Ninety subjects meeting the criteria for amnestic MCI were recruited and followed
      annually for an average of 3.3 years. Main outcome measure was the development of
      dementia determined by clinical assessment with confirmatory neuropsychological
      evaluation. RESULTS: Fifty patients (56%) developed dementia on follow-up. They
      were older, had lower Mini-mental status exam (MMSE) scores and a shorter
      duration of symptoms at the time of first assessment. Multivariate logistic
      regression analysis identified age at symptom onset as the only clinical
      parameter which distinguished the group that deteriorated to dementia from the
      group that did not. The odds ratio for age was 1.1 (confidence interval 1.04 -
      1.18). CONCLUSIONS: Patients presenting with amnestic MCI insufficient for the
      diagnosis of dementia are at high risk of developing dementia on follow-up. In
      our cohort, 56% were diagnosed with dementia over an average period of 5.9 years
      from symptom onset. The only clinical predictor for the eventual development of
      dementia was older age at symptom onset. Clinical features alone were
      insufficient to predict development of dementia.

PMID- 18714800
TI  - RAVLT and nonverbal analog: French forms and clinical findings.
AB  - BACKGROUND: Objective clinical evaluation of memory frequently requires serial
      testing but the issue of whether multi-formed tests are equivalent and can be
      used interchangeably is seldom examined. An added problem in bilingual Canadian
      settings is the extent to which it is appropriate to measure French speakers'
      performance on translations of English tests. The present work used the Rey
      Auditory Verbal Learning Test (RAVLT) and a nonverbal analog, the Aggie Figures
      Learning Test (AFLT), to examine whether a) different forms of the same test are
      equivalent, b) performance on the two tests is comparable, c) two language groups
      perform similarly, and d) the RAVLT can detect dysfunction in patients with
      temporal lobe epilepsy (TLE). METHODS: We compared three French versions of the
      RAVLT and three forms of the AFLT in 114 healthy francophone adults. We
      subsequently compared the performance of the same francophone subjects to a
      previously obtained sample of anglophones on both tests, and then administered
      the RAVLT to anglophone or francophone patients with TLE. RESULTS: For both tasks
      the three forms were equivalent and performance on the RAVLT was comparable to
      that on the AFLT. Francophone subjects performed slightly worse on the RAVLT
      compared to anglophones but performance of the two language groups did not differ
      on the AFLT. Finally, left TLE patients were impaired compared to right on the
      RAVLT, but no performance differences were observed across the two language
      groups in the patient sample. CONCLUSIONS: The RAVLT and AFLT are useful tools
      for examination of learning and memory in French and English speaking
      populations. On the RAVLT, the lesion effect in patients is not affected by
      differences in performance between language groups.

PMID- 18714801
TI  - A novel mutation in a large French-Canadian family with LGMD1B.
AB  - BACKGROUND: Limb girdle muscular dystrophy type 1B is an autosomal dominant
      disease characterized by late onset proximal muscle involvement associated with
      cardiac complications such as atrioventricular conduction blocks, dilated
      cardiomyopathy, and sudden death. OBJECTIVE: Define the full phenotypic spectrum
      of a new mutation in the LMNA gene causing limb girdle muscular dystrophy type
      1B. METHODS: We identified a large French Canadian family with the LGMD 1B
      phenotype and a cardiac conduction disease phenotype that carried a new mutation
      in the LMNA gene and sought to define its full phenotypic spectrum by performing
      complete neurological and cardiac evaluations, muscle biopsy, RNA and DNA
      studies. RESULTS: The proband and 12 living at risk relatives were tested. In
      total, we identified seven carriers of a new (IVS9-3C > G) LMNA gene mutation. Of
      the three symptomatic patients, all had cardiac involvement, but only two
      presented proximal limb weakness. The one available muscle biopsy demonstrated a
      normally expressed lamin A/C protein, localized at the nuclear envelope. RNA
      study revealed a loss of exon 10 transcription caused by the IVS9-3C to G
      splicing mutation. CONCLUSIONS: We have identified a new mutations in the LMNA
      gene in a French-Canadian family. This diagnosis has important implications for
      affected patients and their siblings since they may eventually require pacemaker
      implantation.

PMID- 18714802
TI  - Diagnostic accuracy of neurological problems in the emergency department.
AB  - BACKGROUND: Previous studies describe significant rates of misdiagnosis of
      stroke, seizure and other neurological problems, but there are few studies
      examining diagnostic accuracy of all emergency referrals to a neurology service.
      This information could be useful in focusing the neurological education of
      physicians who assess and refer patients with neurological complaints in
      emergency departments. METHODS: All neurological consultations in the emergency
      department at a tertiary-care teaching hospital were recorded for six months. The
      initial diagnosis of the requesting physician was recorded for each patient. This
      was compared to the initial diagnosis of the consulting neurologist and to the
      final diagnosis, as determined by retrospective chart review. RESULTS: Over a six
      month period, 493 neurological consultations were requested. The initial
      diagnosis of the requesting physician agreed with the final diagnosis in 60.4%
      (298/493) of cases, and disagreed or was uncertain in 35.7% of cases (19.1% and
      16.6% respectively). In 3.9% of cases, the initial diagnosis of both the
      referring physician and the neurologist disagreed with the final diagnosis.
      Common misdiagnoses included neurocardiogenic syncope, peripheral vertigo,
      primary headache and psychogenic syndromes. Often, these were initially diagnosed
      as stroke or seizure. CONCLUSIONS: Our data indicate that misdiagnosis or
      diagnostic uncertainty occurred in over one-third of all neurological
      consultations in the emergency department setting. Benign neurological
      conditions, such as migraine, syncope and peripheral vertigo are frequently
      mislabeled as seizure or stroke. Educational strategies that emphasize emergent
      evaluation of these common conditions could improve diagnostic accuracy, and may
      result in better patient care.

PMID- 18714803
TI  - The prevalence of cerebral palsy in British Columbia, 1991-1995.
AB  - OBJECTIVE: To quantify the prevalence of cerebral palsy (CP) in British Columbia
      within a four-year birth cohort. METHODS: The study was a population-based record
      linkage study of a birth cohort of British Columbian children born between April
      1, 1991 and March 31, 1995. Cases were identified by the presence of
      International Classification of Diseases, Version 9 (ICD-9) diagnostic code "343"
      recorded at three years of age or older or by having the ICD-9 diagnostic code
      "343" recorded prior to the third birthday with two confirmatory diagnoses within
      the first three years of life through a record search of the BC Medical Services
      Plan billing files for the fiscal years 1991 to 1995. RESULTS/CONCLUSION: This
      research has provided an estimate of the prevalence of CP in the four-year birth
      cohort 1991 to 1995 in British Columbia. An aggregate prevalence rate of CP was
      measured as 2.68 per 1000 live births, and a congenital rate was measured at 2.57
      for the same population. Birth weight and gestational age demonstrated a
      significant relationship with the development of CP. This study should lend
      credence to the establishment of a CP register in British Columbia.

PMID- 18714804
TI  - Reliability of point-of-care testing of INR in acute stroke.
AB  - BACKGROUND: In the emergency department, portable point-of-care testing (POCT)
      coagulation devices may facilitate stroke patient care by providing rapid
      International Normalized Ratio (INR) measurement. The objective of this study was
      to evaluate the reliability, validity, and impact on clinical decision-making of
      a POCT device for INR testing in the setting of acute ischemic stroke (AIS).
      METHODS: A total of 150 patients (50 healthy volunteers, 51 anticoagulated
      patients, 49 AIS patients) were assessed in a tertiary care facility. The INR's
      were measured using the Roche Coaguchek S and the standard laboratory technique.
      RESULTS: The interclass correlation coefficient and 95% confidence interval
      between overall POCT device and standard laboratory value INRs was high (0.932
      (0.69 - 0.78). In the AIS group alone, the correlation coefficient and 95% CI was
      also high 0.937 (0.59 - 0.74) and diagnostic accuracy of the POCT device was 94%.
      CONCLUSIONS: When used by a trained health professional in the emergency
      department to assess INR in acute ischemic stroke patients, the CoaguChek S is
      reliable and provides rapid results. However, as concordance with laboratory INR
      values decreases with higher INR values, it is recommended that with CoaguChek S
      INRs in the > 1.5 range, a standard laboratory measurement be used to confirm the
      results.

PMID- 18714805
TI  - Restless legs syndrome in patients with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To evaluate the prevalence of restless legs syndrome (RLS) in patients
      with chronic obstructive pulmonary disease (COPD) and the relationship between
      RLS and clinical/laboratory findings of COPD. METHODS: One hundred and thirty
      four COPD patients without secondary causes of RLS were included. Thirty-nine
      (29.1%) patients were diagnosed with RLS and classified as Group 1. The control
      group consisted of 65 age-matched COPD patients without RLS. Group 1 was divided
      into subgroups according to the Johns Hopkins Severity (JHS) scale. Patients with
      a score of 0, 1, or 2 were classified as JHS 0-2 and those with a score of 3 as
      JHS 3. Group 1 and the control group and subgroups were compared for clinical and
      laboratory characteristics. RESULTS: We found that the duration of COPD was
      longer and that airway obstruction, hypercapnia, and hypoxia were more evident in
      patients with RLS than those without. Similar differences were also detected
      between JHS subgroups 3 (more severe) and 0-2. Polyneuropathy frequency was
      significantly higher in Group 1 compared to controls. However, Group 1 subgroups
      showed a similar frequency of polyneuropathy. In a multivariate analysis,
      hypercapnia made a significant independent contribution to both JHS 0-2 and JHS 3
      patients when RLS severity was set as the dependent variable. Polyneuropathy and
      the duration of COPD were significant independent variables for patients in the
      JHS 3 subgroup. Polyneuropathy was the strongest predictor for the JHS 3
      patients. CONCLUSIONS: We conclude that RLS is frequent in COPD, particularly in
      patients with severe hypoxemia/hypercapnia and in late stages of the disease.

PMID- 18714806
TI  - Recurrent thalamic haemorrhage attributed to a cerebellar arteriovenous
      malformation.

PMID- 18714807
TI  - A case of foreign accent syndrome resulting in regional dialect.
AB  - BACKGROUND: Foreign Accent Syndrome (FAS) is a rare acquired syndrome following
      neurological damage that results in articulatory distortions that are commonly
      perceived as a "foreign" accent. The nature of the underlying deficit of FAS
      remains controversial. We present the first reported Canadian case study of FAS
      following a stroke. We describe a stroke patient, RD, who suffered an acute
      infarction to the left internal capsule, basal ganglia and frontal corona
      radiata. She was diagnosed as having FAS without any persistent aphasic symptoms.
      Family, friends, and health care professionals similarly described her speech as
      sounding like she had a Canadian East Coast accent, a reported change from her
      native Southern Ontario accent. METHOD: An investigation of this case was
      pursued, incorporating neuroimaging, neuropsychological and speech pathology
      assessments, and formalized linguistic analyses. RESULTS: Linguistic analyses
      confirmed that RD's speech does in fact have salient aspects of Atlantic Canadian
      English in terms of both prosodic and segmental characteristics. However, her
      speech is not entirely consistent with an Atlantic Canadian English accent.
      INTERPRETATION: The fact that RD's speech is perceived as a regional variant of
      her native language, rather than the "generic foreign accent" of FAS described
      elsewhere, suggests that the perceived "foreignness" in FAS is not primarily due
      to dysfluencies which indicate a non-native speaker, but rather due to very
      subtle motor-planning deficits which give rise to systemic changes in specific
      phonological segments. This has implications for the role of the basal ganglia in
      speech production.

PMID- 18714808
TI  - Intravascular lymphoma with conus medullaris syndrome followed by encephalopathy.
AB  - BACKGROUND: Intravascular large cell lymphoma (ILCL) is a diagnostic challenge,
      with neurological, cutaneous and constitutional symptoms. The natural history is
      usually an evolution to a comatose state. As invasive procedures are usually
      required for diagnosis, recognizing the typical clinical pattern is critical
      since an effective treatment is available. METHOD: After an extensive literature
      review of the subject, we report a case of ILCL, analyzing clinical, laboratory,
      radiological and pathological data. We will also give a special attention to the
      clinical picture of a conus medullaris (CM) lesion with subsequent encephalopathy
      in the same patient, RESULTS: We report here a 61-year-old woman with a
      paraplegia caused by a CM lesion, evolving about one year latter to
      encephalopathy and eventual coma, with the diagnosis of ILCL confirmed by
      autopsy. The present case is similar to eight other cases in literature who had
      CM lesion associated with ILCL, knowing that 80-90% of these patients will
      eventually evolve to encephalopathy without treatment. CONCLUSIONS: ILCL is a
      recognized but rare cause of coma. Diagnosing it is tremendously important since
      it is fatal if left untreated. We propose that this specific picture (conus
      medullaris lesion, eventually evolving to encephalopathy) is quite characteristic
      and will directly result in better outcome if recognized.

PMID- 18714809
TI  - A V139M mutation also causes the reversible CNS phenotype in CMTX.

PMID- 18714810
TI  - Solitary myofibroma of the skull presenting outside infancy.

PMID- 18714811
TI  - Internal carotid artery septa in sickle cell disease: risk factor for stroke?

PMID- 18714812
TI  - Sphenoid sinus mucocele--rupture causing brainstem inflammation and stroke.
AB  - BACKGROUND: Posterior rupture of a sphenoid sinus mucocele is a rare cause of
      brainstem injury. METHODS: Case report. RESULTS: A healthy young woman with a
      history of prior surgical excision of nasal polyps presented with a headache and
      evolving neurologic symptoms. The clinical presentation and imaging studies were
      consistent with a posterior rupture of a large sphenoid mucocele with subsequent
      inflammatory changes in the brainstem and evidence of brainstem stroke.
      Relatively rapid recovery coincided temporally with the resolution of local
      inflammation. Longer-term recovery continued over months, as expected following
      stroke. CONCLUSIONS: Posterior rupture of a sphenoid sinus mucocele may cause
      brainstem injury by multiple mechanisms.

PMID- 18714813
TI  - Diesel pollution biodegradation: synergetic effect of Mycobacterium and
      filamentous fungi.
AB  - OBJECTIVE: To biodegrade the diesel pollution in aqueous solution inoculated with
      Mycobacterium and filamentous fungi. METHODS: Bacteria sampled from petroleum
      hydrocarbons contaminated sites in Karamay Oilfield were isolated and identified
      as Mycobacterium hyalinum (MH) and cladosporium. Spectrophotometry and gas
      chromatography (GC) were used to analyze of the residual concentrations of diesel
      oil and its biodegradation products. RESULTS: From the GC data, the values of
      apparent biodegradation ratio of the bacterial strain MH to diesel oil were close
      to those obtained in the control experiments. Moreover, the number of MH did not
      increase with degradation time. However, by using n-octadecane instead of diesel
      oil, the real biotic degradation ratio increased to 20.9% over 5 days of
      degradation. Cladosporium strongly biodegraded diesel oil with a real degradation
      ratio of up to 34% after 5 days treatment. When the two strains were used
      simultaneously, a significant synergistic effect between them resulted in almost
      complete degradation of diesel oil, achieving a total diesel removal of 99% over
      5 days of treatment, in which one part of about 80% and another part of about 19%
      were attributed to biotic and abiotic processes, respectively. CONCLUSION: The
      observed synergistic effect was closely related to the aromatics-degrading
      ability of Cladosporium, which favored the growth of MH and promoted the
      bioavailability of diesel oil.

PMID- 18714814
TI  - Association of ghrelin polymorphisms with metabolic syndrome in Han Nationality
      Chinese.
AB  - OBJECTIVE: To investigate the association of ghrelin gene polymorphisms with
      metabolic syndrome in Han Nationality Chinese. METHODS: A total of 240 patients
      with metabolic syndrome and 427 adults aged above forty years were recruited.
      Genotypes were determined by polymerase chain reaction and restriction fragment
      length polymorphism analysis. RESULTS: The allelic frequency of the Leu72Met
      polymorphism was 17.3% in the patient group and 11.9% in the control group (chi2
      = 7.36, P = 0.007). Metabolic syndrome was more prevalent among carriers of the
      Met72 variant (43.8 vs 33.1%, age- and sex-adjusted odds ratio = 1.57, P = 0.01).
      No Arg51Gln variants were found in our study subjects. CONCLUSION: Rather than
      being associated with its individual components, Leu72Met polymorphism is
      associated with metabolic syndrome in the Han Nationality Chinese. Arg51Gln
      polymorphism is rare in the Han Nationality Chinese.

PMID- 18714815
TI  - Prediction of toxicity of phenols and anilines to algae by quantitative structure
      activity relationship.
AB  - OBJECTIVE: To measure the toxicity of phenol, aniline, and their derivatives to
      algae and to assess, model, and predict the toxicity using quantitative structure
      activity relationship (QSAR) method. METHODS: Oxygen production was used as the
      response endpoint for assessing the toxic effects of chemicals on algal
      photosynthesis. The energy of the lowest unoccupied molecular orbital (E(LUMO))
      and the energy of the highest occupied molecular orbital (E(HOMO)) were obtained
      from the ChemOffice 2004 program using the quantum chemical method MOPAC, and the
      frontier orbital energy gap (deltaE) was obtained. RESULTS: The compounds
      exhibited a reasonably wide range of algal toxicity. The most toxic compound was
      alpha-naphthol, whereas the least toxic one was aniline. A two-descriptor model
      was derived from the algal toxicity and structural parameters: log1/EC50 =
      0.268,logKow - 1.006deltaE + 11.769 (n = 20, r2 = 0.946). This model was stable
      and satisfactory for predicting toxicity. CONCLUSION Phenol, aniline, and their
      derivatives are polar narcotics. Their toxicity is greater than estimated by
      hydrophobicity only, and addition of the frontier orbital energy gap deltaE can
      significantly improve the prediction of logKow-dependent models.

PMID- 18714816
TI  - Developmental and reproductive toxicity of soybean isoflavones to immature SD
      rats.
AB  - OBJECTIVE: To investigate the dose-dependent toxic effect of soybean isoflavone
      extracts (SIE) on reproductive development in immature rats. METHODS: Growing
      male and female rats (n = 50 each, 4 weeks) were divided into five groups fed
      with a standard cereal-based diet and gastrogavaged daily with 0, 30, 150, 300,
      and 600 mg SIE/kg body weight, respectively, for 12 weeks. Body weight, organ
      weights, and serum level of estrogen and testosterone were measured. RESULTS:
      Oral administration of SIE had no effect on food intake but decreased food
      efficiency ratio (P < 0.01). Suppression on body weight gain by SIE was dose
      dependent and the effect was greater on male than on female rats (P < 0.01). SIE
      at high doses exhibited hepatotoxicity by increasing a relative liver weight, and
      also caused a smaller uterus but a greater relative ovary in female rats, while
      leading to larger relative testis and epididymis in male rats. SIE could decrease
      progesterone concentrations in female rats, whereas in male rats it reduced not
      only total testosterone level but also sperm count compared with the control
      group (P < 0.05). CONCLUSION: SIE at a range of 50-1000 times of human intake
      level affects not only growth but also development of reproductive system in
      growing rats.

PMID- 18714817
TI  - Cancer mortality and asbestosis among workers in an asbestos plant in Chongqing,
      China.
AB  - OBJECTIVE: To investigate whether asbestosis is a risk factor for mortality of
      lung cancer. METHODS: A fixed cohort study was established in an asbestos plant
      in Chongqing, China, and followed up for 30 years from the beginning of 1972.
      Basic personal information on life state, cause of death, and diagnosis of
      asbestosis was collected. Multiple logistic regressions were applied to analyze
      risk factors. RESULTS: During the 30-year follow-up, 584 male workers
      constituting a total of 14,664 person-years were monitored and data were
      analyzed. Among them, 203 (34.8%) died and the mortality rate was 13.8 per 1000
      person-years, cancer accounting for 37.4%. Excess risks were observed for lung
      cancer (OR = 3.72) and nonmalignant respiratory diseases (OR = 2.73) among
      workers with asbestosis. High-exposure level was another risk factor for lung
      cancer (OR = 3.20). Workers with category II of asbestosis demonstrated a higher
      OR of both lung cancer and nonmalignant respiratory diseases than those with
      category I of asbestosis. CONCLUSION: High asbestos exposure level and asbestosis
      were the risk factors for death of lung cancer and nonmalignant respiratory
      diseases. Asbestosis is an independent risk factor for lung cancer among Chinese
      workers exposed to chrysotile, the risk increases with the increasing profusion
      of opacities of lung.

PMID- 18714818
TI  - Reversal of apoptotic resistance by Lycium barbarum glycopeptide 3 in aged T
      cells.
AB  - OBJECTIVE: To study whether Lycium barbarum glycopeptide 3 (LBGP3) affects T cell
      apoptosis in aged mice. METHODS: LBGP3 was purified with DEAE cellulose and
      Sephadex columns. Apoptotic "sub-G1 peak" was detected by flow cytometry and DNA
      ladder was resolved by agarose gel electrophoresis. Levels of IFN-gamma and IL-10
      were measured with specific kits and mRNA expression was detected by RT-PCR.
      Apoptosis-related proteins of FLIP, FasL, and Bcl-2 were determined by Western
      blotting. RESULTS: LBGP3 was purified from Fructus Lycii water extracts and
      identified as a 41 kD glycopeptide. Treatment with 200 microg/mL LBGP3 increased
      the apoptotic rate of T cells from aged mice and showed a similar DNA ladder
      pattern to that in young T cells. The reversal of apoptotic resistance was
      involved in down-regulating the expression of Bcl-2 and FLIP, and up-regulating
      the expression of FasL. CONCLUSION: Lycium barbarum glycopeptide 3 reverses
      apoptotic resistance of aged T cells by modulating the expression of apoptosis
      related molecules.

PMID- 18714819
TI  - Effect of electromagnetic pulse exposure on permeability of blood-testicle
      barrier in mice.
AB  - OBJECTIVE: To study the effect of electromagnetic pulse (EMP) exposure on the
      permeability of blood-testicle barrier (BTB) in mice. METHODS: Adult male BALB/c
      mice were exposed to EMP at 200 kV/m for 200 pulses with 2 seconds interval. The
      mice were injected with 2% Evans Blue solution through caudal vein at different
      time points after exposure, and the permeability of BTB was monitored using a
      fluorescence microscope. The testis sample for the transmission electron
      microscopy was prepared at 2 h after EMP exposure. The permeability of BTB in
      mice was observed by using Evans Blue tracer and lanthanum nitrate tracer.
      RESULTS: After exposure, cloudy Evans Blue was found in the testicle convoluted
      seminiferous tubule of mice. Lanthanum nitrate was observed not only between
      testicle spermatogonia near seminiferous tubule wall and sertoli cells, but also
      between sertoli cells and primary spermatocyte or secondary spermatocyte. In
      contrast, lanthanum nitrate in control group was only found in the testicle
      sertoli cells between seminiferous tubule and near seminiferous tubule wall.
      CONCLUSION: EMP exposure could increase the permeability of BTB in the mice.

PMID- 18714820
TI  - Renal protective activity of Hsian-tsao extracts in diabetic rats.
AB  - OBJECTIVE: To investigate the renal protective activity of Hsian-tsao Mesona
      procumbens Hemsl. water extracts in diabetic rats. METHODS: Thirty Sprague-dawley
      female rats were randomly divided into three groups (n = 10 each), "control
      group" with intraperitoneal saline injection, "diabetic group" with 60 mg of
      intraperitoneal streptozotocin injection per kg of body weight and "Hsian-tsao
      group" with intragastric administration of Hsian-tsao extraction everyday for 4
      weeks after intraperitoneal streptozotocin injection. The body weight and blood
      sugar were measured before and after model induction in the three groups.
      Thrombospondin-1 (TSP-1) expressions in the kidney were monitored by
      immunohistochemistry. Kidney ultrastructural changes were also analyzed by using
      transmission electron microscopy. RESULTS: Before diabetic model induction, there
      were no significant differences among the three groups in body weight and blood
      sugar. Four weeks after the induction of diabetes, the differences became
      statistically significant. Electron microscopy also revealed disruption of the
      foot processes of the podocytes and other damages in diabetic group. These
      damages were significantly less severe in Hsian-tsao group when compared with the
      diabetic group. TSP-1 expressions in the kidney were significantly increased in
      both the diabetic group and Hsian-tsao group, but it was relatively lower in
      Hsian-tsao group than in diabetic group. CONCLUSION: Our results showed that
      Hsian-tsao treatment in the diabetic rats effectively prevented the pathological
      alterations in the kidney and decreased the TSP-1 expression. It was suggested
      that Hsian-tsao had protective effect on the kidneys of the diabetic rats.

PMID- 18714821
TI  - Parental anxiety and quality of life of epileptic children.
AB  - OBJECTIVE: To investigate the prevalence of parental anxiety associated with
      epileptic children, and to explore whether and how this specific condition
      affects children's quality of life (QOL), and what are the significant
      determinants for parental anxiety. METHODS: Three hundred and forty parents whose
      children were affected with known epilepsy were enrolled in the study.
      Questionnaires for quality of life in childhood epilepsy (QOLCE), and hospital
      anxiety and depression (HAD) of parents were used to collect demographic data of
      both children and their parents, as well as clinical manifestations of epilepsy
      and family status. RESULTS: Parental anxiety (of any severity) was observed in
      191 subjects at interview, giving a prevalence rate of 56.2%. Of the 191
      subjects, 18.5% reported mild anxiety, 24.4% moderate anxiety, and 13.2% severe
      anxiety. Factors associated with parental anxiety included frequency of seizure
      in children, average monthly income per person and parents' knowledge about
      epilepsy (P < 0.05). Parental anxiety significantly (P = 0.000) correlated with
      quality of life of children with epilepsy. CONCLUSION: Parents of children with
      epilepsy are at high risk of having anxiety. Factors associated with parental
      anxiety originate both from children and from parents. Parental anxiety is
      significantly related with children's QOL. It is important for experts concerned
      to recognize such a relationship to improve the QOL of children and their
      parents.

PMID- 18714822
TI  - Catalytic metalloporphyrin protects against paraquat neurotoxicity in vivo.
AB  - OBJECTIVE: To examine the neuroprotective effects of a novel manganese porphyrin,
      manganese (III) meso-tetrakis (N,N'-diethylimidazolium-2-yl) porphyrin (MnTDM),
      in the mouse model of Parkinson's disease (PD) induced by paraquat (PQ). METHODS:
      Male C57BL/6 mice were subcutaneously injected with either saline or PQ at 2-day
      intervals for a total of 10 doses, MnTDM was subcutaneously injected with the PQ
      2 h before treatment. Performance on the pole and swim test were measured 7 days
      after the last injection and animals were sacrificed one day later. Levels of
      dopamine (DA) and its metabolites in the striatum were measured by high
      performance liquid chromatography with an electrochemical detector (HPLC-ECD).
      Thiobarbituric acid (TBA) method was used to assay the lipid peroxidation
      product, malondialdehyde (MDA), and the number of tyrosine hydroxylase (TH)
      positive neurons was estimated using immunohistochemistry. RESULTS: Pretreatment
      with MnTDM significantly attenuated PQ-impaired behavioral performance, depleted
      dopamine content in striata, increased MDA, and dopaminergic neuron loss in the
      substantia nigra. CONCLUSIONS: Oxidative stress plays an important role in PQ
      induced neurotoxicity which can be potentially prevented by manganese porphyrin.
      These findings also propose a possible therapeutical strategy for
      neurodegenerative disorders associated with oxidative stress such as PD.

PMID- 18714823
TI  - Job stress, gene polymorphism of beta2-AR, and prevalence of hypertension.
AB  - OBJECTIVE: To study the interactive effect of job stress and genetic
      susceptibility (or gene polymorphism) on hypertension. METHODS: A cross-sectional
      epidemiological study was conducted in 452 workers from a thermal power plant in
      China. Extrinsic effort, occupational reward, and over-commitment were measured.
      Hypertensive patients were defined by three phases of screening, reexamination,
      and final diagnosis. beta2-AR genotypes and allele frequencies at amino acid
      positions 16 (beta2-AR-16: Arg-->Gly) and 27 (beta2-AR-27: Gln-->Glu) were
      identified by PCR-RFLP. RESULTS: Job stress was related with the prevalence of
      hypertension in males (P < 0.05), whereas no significant relationship was found
      in females (P > 0.05). Differences in genotypes and allele frequencies of the
      beta2-AR-16 were statistically significant between the hypertension and control
      groups (P < 0.05), whereas those of beta2-AR-27 were not (P > 0.05). The
      prevalence of hypertension was higher in individuals carrying Gly16 allele than
      in those carrying Arg16 allele of the high job stress group (P < 0.01 or 0.05).
      CONCLUSION: High job stress and polymorphism of beta2-AR-16 have an interactive
      effect on the prevalence of hypertension in male workers.

PMID- 18714824
TI  - Validity of diagnostic evidence for deceased cases in hospitals.
AB  - OBJECTIVE: To determine the validity of the diagnostic evidence for deceased
      cases in hospitals. METHODS: All information collected from medical records of
      the deceased cases in tertiary care health facilities was input into our
      database. Four diagnosis levels were determined based on level of diagnostic
      evidence: level I was based on autopsy, pathology or operative exploration, level
      II on physical and laboratory tests plus expert clinical judgment, level III on
      expert clinical judgment, level IV on postmortem assumptions. After the
      diagnostic evidence of each deceased case was reviewed by a panel of three
      experts, the diagnostic level of each diagnosis was determined. RESULTS: Among
      the 2102 medical cases for verbal autopsy study, only 26 (1.24%) afforded
      diagnostic evidence for level III. Among the level III evidence-based cases of
      death, the major causes of death were cardiovascular diseases, respiratory
      diseases, and gastroenterological diseases. According to some special symptoms
      and medical histories, these cases could be diagnosed by comprehensive clinical
      judgment. Only one case met the criteria for level IV. CONCLUSION: Level I
      diagnostic evidence is hard to attain in China because of the traditional concept
      and economic restriction. The causes for 2101 deaths can be validated by level II
      or III diagnostic evidence.

PMID- 18714825
TI  - Trends in suicide by poisoning in China 2000-2006: age, gender, method, and
      geography.
AB  - OBJECTIVE: This study analyzed patterns of suicide and suicide attempts by
      poisoning as reported through a national poison control system for the purpose of
      improving intervention and prevention. METHODS: During the period of 2000 to
      2006, 6440 cases of poisoning suicide were reported to the telephone consultation
      service system of The National Center for Poisoning Control (Chinese Center for
      Disease Control and Prevention). Among these records, 4728 cases had completed
      data for this analysis in terms of age, sex, trend of time and location, and type
      of poisons. RESULTS: There were 60.6% female cases with the age from 10 to 90
      years old. The age of cases from 20 to 39 years accounted for 54.5% of all age
      groups. Both the numbers and percentage in record related to poisoning
      consultation of oral poisoning suicide showed an increasing tendency during the 7
      years. In particular, there was a drastic increase from 2004 to 2006. In
      addition, the high frequency of cases occurred from May to October. Hebei,
      Shandong, Henan, and Anhui Provinces had the highest number of cases. Pesticide
      poisonings were the most common method in these cases of consultation for suicide
      and suicide attempts. CONCLUSION: This study describes epidemiological
      characteristics in the oral poisoning suicide cases and provides scientific basis
      for suicide prevention interventions.

PMID- 18714826
TI  - Exploring barriers to implementation of smoking policies: a qualitative study on
      health professionals from three county-level hospitals.
AB  - OBJECTIVE: This study was to identify factors limiting the implementation of
      smoking policies in county-level hospitals. METHODS: We conducted qualitative
      interviews (17 focus groups discussions and 6 one-to-one in depth interviews)
      involving 103 health professionals from three target county-level hospitals. A
      combination of purposive and convenience sampling was used to recruit subjects
      and gain a broad range of perspectives on issues emerging from ongoing data
      analysis until data saturation occurred. The transcripts were analyzed for themes
      and key points. RESULTS: The main themes that emerged suggested that both smokers
      and non-smokers viewed smoking very negatively. However, it was clear that,
      underlying this acceptance of the health risks of smoking, there was a wide range
      of beliefs. Most of the health professionals pointed out that, as smoking was
      legal, addictive, and influenced by social norms, currently it was almost
      unrealistic to expect all smokers to give up smoking or not to smoke in the
      hospitals. Furthermore, they were concerned about the potentially detrimental
      effects of providing counseling advice to all smokers on the interpersonal
      relationship among colleagues or between doctors and patients. In addition, low
      level of employee participation influenced the sustainable implementation of
      smoking policies. CONCLUSIONS: Simply being aware of the health risks about
      smoking did not necessarily result in successful implementation of the smoking
      policies. Application of comprehensive intervention strategies such as
      implementing smoking policies in public places at the county level, creating
      supportive environments, promoting community participation, and conducting health
      education, may be more effective.

PMID- 18714827
TI  - Complementary feeding and growth of infant and young child in China.
AB  - OBJECTIVE: To understand the status and problems of complementary feeding and to
      explore the strategy of improving complementary feeding for infants and young
      children in China. METHOD: Data of urban and rural children were selected from
      the China Food and Nutrition Surveillance System (CFNSS) dataset to describe the
      status of complementary feeding and growth of children. Logistic Regression was
      used to analyze the relationship between child growth and the complementary
      feeding pattern. RESULTS: Applications of foods that come from animals,
      vegetable/fruit and dairy product in complementary feeding were negatively
      correlated to the prevalence of stunting and underweight. Attributable risk (AR)
      of no application of vegetable/fruit in complementary feeding to stunting was
      30.2%, to underweight 35.4%; AR of no application of foods from animal products
      in complementary feeding to stunting was 28.2%, to underweight 11.7%; and the AR
      of no application of diary products in complementary feeding to stunting was
      27.4%, to underweight was 15.9%. CONCLUSION: Complementary feeding contributed to
      the improvement of infants and young children growth in China. There is an urgent
      need to develop health education in the public on infants and young children
      complementary feeding, in the mean time, it is pressing to pay attention and take
      actions to develop and promote affordable, acceptable, and accessible fortified
      complementary food in rural areas of China.

PMID- 18714828
TI  - Simulation of surface EMG signals for a multilayer volume conductor with a
      superficial bone or blood vessel.
AB  - This study analytically describes surface electromyogram (EMG) signals generated
      by a planar multilayer volume conductor constituted by different subdomains
      modeling muscle, bone (or blood vessel), fat, and skin tissues. The bone is
      cylindrical in shape, with a semicircular section. The flat portion of the
      boundary of the bone subdomain is interfaced with the fat layer tissue, the
      remaining part of the boundary is in contact with the muscle layer. The volume
      conductor is a model of physiological tissues in which the bone is superficial,
      as in the case of the tibia bone, backbone, and bones of the forearm. The muscle
      fibers are considered parallel to the axes of the bone, so that the model is
      space invariant in the direction of propagation of the action potential. The
      proposed model, being analytical, allows faster simulations of surface EMG with
      respect to previously developed models including bone or blood vessels based on
      the finite-element method. Surface EMG signals are studied by simulating a
      library of single-fiber action potentials (SFAP) of fibers in different locations
      within the muscle domain, simulating the generation, propagation, and extinction
      of the action potential. The decay of the amplitude of the SFAPs in the direction
      transversal to the fibers is assessed. The decay in the direction of the bone has
      a lower rate with respect to the opposite direction. Similar results are obtained
      by simulating motor unit action potentials (MUAPs) constituted by 100 fibers with
      territory 5 mm2. M waves and interference EMG signals are also simulated based on
      the library of SFAPs. Again, the decay of the amplitude of the simulated
      interference EMG signals is lower approaching the bone with respect to going
      farther from it. The findings of this study indicate the effect of a superficial
      bone in enhancing the EMG signals in the transversal direction with respect to
      the fibers of the considered muscle. This increases the effect of crosstalk. The
      same mathematical method used to simulate a superficial bone can be applied to
      simulate other physiological tissues. For example, superficial blood vessels
      (e.g., basilic vein, brachial artery) can influence the recorded EMG signals. As
      the electrical conductivity of blood is high (it is of the same order as the
      longitudinal conductivity in the muscle), the effect on EMG signals is opposite
      compared to the effect of a superficial bone.

PMID- 18714829
TI  - Spectral and nonlinear analyses of MEG background activity in patients with
      Alzheimer's disease.
AB  - The aim of the present study is to analyze the magnetoencephalogram (MEG)
      background activity from patients with Alzheimer's disease (AD) and elderly
      control subjects. MEG recordings from 20 AD patients and 21 controls were
      analyzed by means of two spectral [median frequency (MF) and spectral entropy
      (SpecEn)] and two nonlinear parameters [approximate entropy (ApEn) and Lempel-Ziv
      complexity (LZC)]. In the AD diagnosis, the highest accuracy of 75.6% (80%
      sensitivity, 71.4% specificity) was obtained with the MF according to a linear
      discriminant analysis (LDA) with a leave-one-out cross-validation procedure.
      Moreover, we wanted to assess whether these spectral and nonlinear analyses could
      provide complementary information to improve the AD diagnosis. After a forward
      stepwise LDA with a leave-one-out cross-validation procedure, one spectral (MF)
      and one nonlinear parameter (ApEn) were automatically selected. In this model, an
      accuracy of 80.5% (80.0% sensitivity, 81.0% specificity) was achieved. We
      conclude that spectral and nonlinear analyses from spontaneous MEG activity could
      be complementary methods to help in AD detection.

PMID- 18714830
TI  - Band expansion-based over-complete independent component analysis for
      multispectral processing of magnetic resonance images.
AB  - Independent component analysis (ICA) has found great promise in magnetic
      resonance (MR) image analysis. Unfortunately, two key issues have been overlooked
      and not investigated. One is the lack of MR images to be used to unmix signal
      sources of interest. Another is the use of random initial projection vectors by
      ICA, which causes inconsistent results. In order to address the first issue, this
      paper introduces a band-expansion process (BEP) to generate an additional new set
      of images from the original MR images via nonlinear functions. These newly
      generated images are then combined with the original MR images to provide
      sufficient MR images for ICA analysis. In order to resolve the second issue, a
      prioritized ICA (PICA) is designed to rank the ICA-generated independent
      components (ICs) so that MR brain tissue substances can be unmixed and separated
      by different ICs in a prioritized order. Finally, BEP and PICA are combined to
      further develop a new ICA-based approach, referred to as PICA-BEP to perform MR
      image analysis.

PMID- 18714831
TI  - Breast surface estimation for radar-based breast imaging systems.
AB  - Radar-based microwave breast-imaging techniques typically require the antennas to
      be placed at a certain distance from or on the breast surface. This requires
      prior knowledge of the breast location, shape, and size. The method proposed in
      this paper for obtaining this information is based on a modified tissue sensing
      adaptive radar algorithm. First, a breast surface detection scan is performed.
      Data from this scan are used to localize the breast by creating an estimate of
      the breast surface. If required, the antennas may then be placed at specified
      distances from the breast surface for a second tumor-sensing scan. This paper
      introduces the breast surface estimation and antenna placement algorithms.
      Surface estimation and antenna placement results are demonstrated on three
      dimensional breast models derived from magnetic resonance images.

PMID- 18714832
TI  - Chromatographic pattern classification.
AB  - In this paper, we propose and evaluate methodologies for the classification of
      images from thin-layer chromatography. Each individual sample is characterized by
      an intensity profile that is further represented into a feature space. The first
      steps of this process aim at obtaining a robust estimate of the intensity profile
      by filtering noise, reducing the influence of background changes, and by fitting
      a mixture of Gaussians. The resulting profiles are represented by a set of
      appropriate features trying to characterize the state of nature, here spread out
      over four classes, one for normal subjects and the other three corresponding to
      lysosomal diseases, which are disorders responsible for severe nerve
      degeneration. For classification purposes, a novel solution based on a
      hierarchical structure is proposed. The main conclusion of this paper is that an
      automatically generated decision tree presents better results than more
      conventional solutions, being able to deal with the natural imbalance of the data
      that, as consequence of the rarity of lysosomal disorders, has very few
      representative cases in the disease classes when compared with the normal
      population.

PMID- 18714833
TI  - Confocal microwave imaging for breast cancer detection: delay-multiply-and-sum
      image reconstruction algorithm.
AB  - A new image reconstruction algorithm, termed as delay-multiply-and-sum (DMAS),
      for breast cancer detection using an ultra-wideband confocal microwave imaging
      technique is proposed. In DMAS algorithm, the backscattered signals received from
      numerical breast phantoms simulated using the finite-difference time-domain
      method are time shifted, multiplied in pair, and the products are summed to form
      a synthetic focal point. The effectiveness of the DMAS algorithm is shown by
      applying it to backscattered signals received from a variety of numerical breast
      phantoms. The reconstructed images illustrate improvement in identification of
      embedded malignant tumors over the delay-and-sum algorithm. Successful detection
      and localization of tumors as small as 2 mm in diameter are also demonstrated.

PMID- 18714834
TI  - Transmission power requirements for novel ZigBee implants in the gastrointestinal
      tract.
AB  - In this paper, a novel multinode wireless monitoring platform, based on ZigBee
      communication standard, is presented and tested in vivo. The transmission power
      levels needed to establish a reliable connection from the different
      gastrointestinal districts are reported and compared with safety levels from
      international guidelines. These findings can be useful to evaluate the
      effectiveness of a commercial and standardized approach to implantable and
      miniaturized monitoring of physiological parameters.

PMID- 18714835
TI  - Continuous monitoring of electrode-skin impedance mismatch during bioelectric
      recordings.
AB  - In bioelectric recordings, an electrode-skin impedance mismatch leads to a
      reduced common-mode rejection ratio (CMRR) of the amplifier. For this reason, the
      impedance of each individual electrode-skin contact is usually measured prior to
      a recording. The measurement circuit itself degrades the CMRR and is switched off
      during the bioelectric recording. In this paper, we present a new method that
      allows to monitor the electrode-skin impedance in a continuous way without
      reducing the CMRR of the amplifier. The new method is based on an additional
      common-mode signal that is superimposed on the bioelectric signal.

PMID- 18714836
TI  - Decomposition of magnetoencephalographic data into components corresponding to
      deep and superficial sources.
AB  - We extend the signal space separation (SSS) method to decompose multichannel
      magnetoencephalographic (MEG) data into regions of interest inside the head. It
      has been shown that the SSS method can transform MEG data into a signal component
      generated by neurobiological sources and a noise component generated by external
      sources outside the head. In this paper, we show that the signal component
      obtained by the SSS method can be further decomposed by a simple operation into
      signals originating from deep and superficial sources within the brain. This is
      achieved by using a scheme that exploits the beamspace methodology that relies on
      a linear transformation that maximizes the power of the source space of interest.
      The efficiency and accuracy of the algorithm are demonstrated by experiments
      utilizing both simulated and real MEG data.

PMID- 18714837
TI  - A polyimide pressure-contact multielectrode array for implantation along a
      submillimeter neural process in small animals.
AB  - We describe a microelectrode system for recordings from nerve bundles with
      diameters ranging from 20-200 microm. A novel polyimide structure allows for a
      planar microfabricated device to constrain a free neural process against several
      recording sites. This polyimide array contains multiple zigzag vias through which
      a small nerve process may be woven while remaining functionally intact in a live
      preparation. Our electrode construct features the benefits of nerve cuffs (evenly
      spaced electrodes in a polymer) and the functionality of a nerve hook (ability to
      connect to submillimeter processes). The device records extracellular action
      potentials in the red-swamp crayfish, Procambarus clarkii. Action potential
      propagation is monitored at several sites along a constrained nerve in this model
      organism's peripheral nervous system. Details of temporal accuracy and error
      sources in absolute conduction velocity measurements from microelectrode arrays
      are discussed.

PMID- 18714838
TI  - Classifying single-trial EEG during motor imagery by iterative spatio-spectral
      patterns learning (ISSPL).
AB  - In most current motor-imagery-based brain-computer interfaces (BCIs), machine
      learning is carried out in two consecutive stages: feature extraction and feature
      classification. Feature extraction has focused on automatic learning of spatial
      filters, with little or no attention being paid to optimization of parameters for
      temporal filters that still require time-consuming, ad hoc manual tuning. In this
      paper, we present a new algorithm termed iterative spatio-spectral patterns
      learning (ISSPL) that employs statistical learning theory to perform automatic
      learning of spatio-spectral filters. In ISSPL, spectral filters and the
      classifier are simultaneously parameterized for optimization to achieve good
      generalization performance. A detailed derivation and theoretical analysis of
      ISSPL are given. Experimental results on two datasets show that the proposed
      algorithm can correctly identify the discriminative frequency bands,
      demonstrating the algorithm's superiority over contemporary approaches in
      classification performance.

PMID- 18714839
TI  - An in vitro model of a retinal prosthesis.
AB  - Epiretinal prostheses are being developed to bypass a degenerated photoreceptor
      layer and excite surviving ganglion and inner retinal cells. We used custom
      microfabricated multielectrode arrays with 200-microm-diameter stimulating
      electrodes and 10-microm-diameter recording electrodes to stimulate and record
      neural responses in isolated tiger salamander retina. Pharmacological agents were
      used to isolate direct excitation of ganglion cells from excitation of other
      inner retinal cells. Strength-duration data suggest that, if amplitude will be
      used for the coding of brightness or gray level in retinal prostheses, shorter
      pulses (200 micros) will allow for a smaller region in the area of the electrode
      to be excited over a larger dynamic range compared with longer pulses (1 ms).
      Both electrophysiological results and electrostatic finite-element modeling show
      that electrode-electrode interactions can lead to increased thresholds for sites
      half way between simultaneously stimulated electrodes (29.4 +/- 6.6 nC) compared
      with monopolar stimulation (13.3 +/- 1.7 nC, p < 0.02). Presynaptic stimulation
      of the same ganglion cell with both 200- and 10-microm-diameter electrodes
      yielded threshold charge densities of 12 +/- 6 and 7.66 +/- 1.30 nC/cm2,
      respectively, while the required charge was 12.5 +/- 6.2 and 19 +/- 3.3 nC.

PMID- 18714840
TI  - Asynchronous P300-based brain-computer interfaces: a computational approach with
      statistical models.
AB  - Asynchronous control is an important issue for brain-computer interfaces (BCIs)
      working in real-life settings, where the machine should determine from brain
      signals not only the desired command but also when the user wants to input it. In
      this paper, we propose a novel computational approach for robust asynchronous
      control using electroencephalogram (EEG) and a P300-based oddball paradigm. In
      this approach, we first address the mathematical modeling of target P300,
      nontarget P300, and noncontrol signals, by using Gaussian distribution models in
      a support vector margin space. Furthermore, we derive a method to compute the
      likelihood of control state in a time window of EEG. Finally, we devise a
      recursive algorithm to detect control states in ongoing EEG for online
      application. We conducted experiments with four subjects to study both the
      asynchronous BCI's receiver operating characteristics and its performance in
      actual online tests. The results show that the BCI is able to achieve an averaged
      information transfer rate of approximately 20 b/min at a low false positive rate
      (one event per minute).

PMID- 18714841
TI  - Toward an acoustic noninvasive diagnosis of urinary bladder outlet obstruction.
AB  - On average, in aging males, the prostate enlarges (benign prostatic enlargement
      or BPE) and may cause bladder outlet obstruction (BOO). The internationally
      standardized method for diagnosing BOO is based on measurements of urinary flow
      rate and bladder pressure, using a catheter inserted into the bladder via the
      urethra. This method is invasive, time-consuming, and uncomfortable for the
      patient. We are developing a novel diagnostic method based on perineal recording
      of sound during urinary flow. Although it is known that (some aspects of) the
      recorded sound are (among others) related to the degree of obstruction, an exact
      and unique relation allowing derivation of the degree of obstruction from the
      sound recording is not known. In a biophysical model of the urethra, we found
      that the weighted average frequency, the standard deviation, and the skewness of
      the power spectrum are monotonically related to the degree of obstruction. The
      standard deviation was the most significant predictor of BOO (89% correct). Based
      on this model study, we are confident that a simple noninvasive acoustic method
      for diagnosing BOO caused by BPE can be developed. This would lower the threshold
      for urodynamic testing of patients with lower urinary tract symptoms resulting in
      higher therapeutic efficacy.

PMID- 18714842
TI  - A wireless implantable passive microdosimeter for radiation oncology.
AB  - Wireless measurement of ionizing radiation in close proximity or/and within an
      irradiated solid tumor is extremely valuable for dose verification and quality
      control in radiation oncology. For such applications, it is preferable to
      manufacture such sensors using passive components since high levels of ionizing
      radiation can damage active electronics. In addition, passive implementation can
      reduce the cost associated with fabrication and assembly. This paper reports on
      the development of an implantable micro-machined passive LC transponder for in
      situ radiation measurement. Dose measurement is performed by monitoring the
      resonance frequency change associated with the decay of surface change of an
      electret upon exposure to radiation. This is achieved through a micromachned
      capacitor with a movable plate that is partially filled with a Teflon electret
      and connected in parallel with an inductor, thus forming a passive LC tank
      circuit. For an implantable prototype encapsulated in a glass capsule (2.5 mm in
      diameter, 2.8 cm in length), test results show that a dose of 30 Gy (from a Co60
      source) can produce 1.46 MHz frequency shift resulting in a sensitivity of 49
      kHz/Gy.

PMID- 18714843
TI  - Cuffless blood pressure monitoring using hydrostatic pressure changes.
AB  - This paper presents a new principle for noninvasive blood pressure measurements
      through a modified volume-oscillometric technique that eliminates an inflatable
      pressure cuff, and instead takes advantage of natural hydrostatic pressure
      changes caused by raising and lowering the subject's arm. This new methodology
      provides the distinct advantage of using an absolute gauge pressure reference for
      measurements, and does not necessarily require additional actuation.

PMID- 18714844
TI  - Medicines and the kidney.

PMID- 18714845
TI  - Lessons from ONTARGET.
AB  - The recently published results of the ONTARGET trial shed a new light on the
      cardiovascular protection of patients at high risk of a cardiovascular event.
      Despite a number of trials looking at the efficacy of Angiotensin Converting
      Enzyme inhibitors (ACEis) or Angiotensin Receptor Blockers (ARBs) in the
      prevention of cardiovascular events in patients with specific high risk profiles,
      the question of the equivalence of ACEis and ARBs remained unanswered. The
      ONTARGET trial has shown that telmisartan 80 mg administered for a median
      duration of 4.5 years to patients at high risk of developing a major
      cardiovascular event, is equally effective to ramipril 10 mg. In addition,
      telmisartan was slightly better tolerated. The comparator ramipril has been
      chosen as it is currently the gold standard ACEi since the results of the HOPE
      study, in terms of the composite outcome of cardiovascular death, myocardial
      infarction and stroke. Moreover, ONTARGET is the first trial to test the
      hypothesis of superiority of adding an ARB (telmisartan 80 mg) to an ACEi
      (ramipril 10 mg) over the ACEi ramipril monotherapy in cardiovascular protection
      of the same broad range of high-risk patients. Surprisingly, despite a more
      pronounced blood pressure lowering, the combination of the two agents did not
      lead to an additional decrease in the number of events, but had significantly
      more side-effects compared to ramipril monotherapy. ONTARGET is a landmark study,
      performed according to the highest statistical and clinical standards, providing
      compelling evidence and clear answers to two important clinical questions.

PMID- 18714846
TI  - Multiorgan-protective actions of blockers of the renin-angiotensin system,
      statins and erythropoietin: common pleiotropic effects in reno-, cardio- and
      neuroprotection.
AB  - Renal diseases induce nephroprotective measures that may affect the heart, brain
      and other organs. In addition, many cardiovascular and neurological diseases are
      accompanied by renal lesions. For these reasons, multiorgan-protective measures,
      including cardio-, reno- and neuro-protective measures, are necessary to treat
      these diseases. The drugs used in nephrology are often pleiotropic. Although they
      usually address a single organ or tissue, many of them have complex actions that
      may provide multiorgan-protection. The present paper aims to review 3 classes of
      drugs that are commonly prescribed in nephrological practice: statins, RAS
      blockers (such as ACEIs and ARBs) and erythropoietin (EPO). This paper highlights
      the renoprotective actions, as well as those that are protective of the heart,
      brain and other organs, of these drugs at the cellular and molecular level. Their
      protective actions are attributable to their main effects and pleiotropic
      effects. The protective pleiotropic actions of these drugs may be exerted on
      multiple organs, making them multiorgan-protective. Another objective is to
      analyse the shared multiorgan-protective pleiotropic effects of RAS blockers
      (ACEIs and ARBs), statins and erythropoietin. This will allow for the practical
      association of the main renoprotective drugs with multiorgan protection.

PMID- 18714847
TI  - A cost-utility analysis of pregabalin in the management of peripheral neuropathic
      pain.
AB  - OBJECTIVES: To assess the cost per QALY (quality-adjusted life years) of
      pregabalin in the management of peripheral neuropathic pain. METHODS: We compared
      pregabalin on top of "usual care" with "usual care" alone. In this study, usual
      care was defined as a mix of drug therapies, excluding anti-epileptic drugs
      (AEDs), because the latter represented only 9% of current use, and clinical
      evidence of pregabalin was demonstrated versus usual care without anti-epileptic
      drugs. A Markov model was developed to simulate the evolution of a patient cohort
      over 1 year, and applied cycles of 4 weeks. During each cycle, patients remained
      in 1 out of 4 possible states: severe, moderate or mild pain, and therapy
      withdrawal. The health care payers perspective was taken into account. Clinical
      data were obtained from a trial comparing usual care plus placebo to usual care
      plus pregabalin, at either 150, 300, or 300/600 mg/day (the latter depending on
      clearance of creatinin). Resulting effects on pain were transformed into
      transition-probabilities between different pain levels. Cost and SF36 utility
      data of pain levels were obtained from a 1-month observational study in 88
      patients. RESULTS: Usual care resulted in a yearly cost of Euros 6,200 compared
      to Euros 5,984 for an all dose pregabalin-mix, meaning a cost saving of Euros 216
      per patient. Utility increase was 0.01 for the pregabalin-mix (QALY 0.510 usual
      care; 0.520 pregabalin-mix). Monte Carlo analysis showed cost savings were not
      significant. However, the utility gain, albeit small, was statistically
      significant. CONCLUSIONS: Based on this analysis, it may be concluded, that in
      the considered patient population, at the specialist level, pregabalin is at
      least cost neutral to current usual care (without AEDs) and offers a slight but
      significant increase in quality of life.

PMID- 18714848
TI  - Interval cancers in the beginning years of the breast cancer screening programme
      in the Belgian province of Limburg.
AB  - OBJECTIVE: To assess the occurrence of interval breast cancers among those women
      who attended the mammography screening programme in the Belgian province of
      Limburg. Interval cancers are tumours that are being diagnosed before the next
      scheduled screening round and are related to the sensitivity and the screening
      interval. METHODS: Biennial screening is provided to all women aged 50-69. The
      records of the screening programme were linked to those of the cancer registry.
      The interval cancer rate, expressed as a proportion of the underlying (expected)
      breast cancer incidence rate was calculated. The observed interval cancer
      incidence is the number of interval cancers per 10,000 'negative' screening
      tests. RESULTS: The interval cancer rate in the first year was 25.37% for all
      cancers (ductal carcinoma in situ included) and 21.7% when the analysis was
      restricted to invasive tumours. Proportional incidence of interval cancer in the
      second year after screening was 12.02% for all cancers. CONCLUSION: In
      conclusion, the interval cancer rates in the Belgian province of Limburg were
      compatible with the European guidelines. However, increasing the recall rate in
      our programme and systematically reviewing the interval cancers may improve the
      quality of the programme even further.

PMID- 18714849
TI  - Usefulness of FDG-PET to diagnose intravascular lymphoma with encephalopathy and
      renal involvement.
AB  - Intravascular lymphoma (IVL) is a rare subtype of extranodal diffuse large B-cell
      lymphoma. It is characterized by proliferation of neoplastic Lymphoid cells
      almost exclusively within the lumina of small blood vessels. It can affect
      virtually every organ system. Due to its rarity and its diverse and heterogeneous
      clinical presentation, diagnosis is difficult and often made post-mortem. When
      diagnosed early, it is, however, potentially treatable. We present a young woman
      with longstanding constitutional symptoms, positive antinuclear antibody,
      elevated LDH levels and rapidly progressive encephalopathy. FDG-PET scan showed
      intense uptake in the renal cortex, which prompted us to perform a kidney biopsy
      which was compatible with IVL. The value of PET in establishing the diagnosis of
      this rare disease will be discussed.

PMID- 18714850
TI  - Bartonella endocarditis mimicking adult Still's disease.
AB  - We describe the case of a 39-year-old Caucasian woman who was admitted to the
      University Hospital of Antwerp with a clinical picture suggestive of adult
      Still's disease. Even though a transoesophageal echocardiography showed
      endocarditis of the aortic valve, blood cultures remained negative. Additional
      serological testing revealed a positive result for Bartonella henselae. Histology
      of the supraclavicular lymph node showed a reactive lymph node with a positive
      polymerase chain reaction (PCR) for Bartonella henselae. Prednisolone treatment
      was started in a dosage of 10 mg per day and rifampicin 600 mg/d in combination
      with doxycyclin 200 mg/d was given for 6 months. During therapy the patient
      gradually improved and signs of endocarditis disappeared on echocardiography.

PMID- 18714851
TI  - Vertebral osteomyelitis with spinal epidural abscess in two patients with
      Bacteroides fragilis bacteraemia.
AB  - We report 2 cases of vertebral osteomyelitis and contiguous epidural abscess due
      to Bacteroides fragilis with no concomitant or past intra-abdominal infection.
      Decompressive surgery with laminectomy was required for both patients due to the
      occurrence of neurologic deficits. Clinical recovery was achieved after 8 weeks
      of antibiotic therapy. It included 3 weeks of intravenous therapy with
      clindamycin followed by an oral regimen of clindamycin for 1 patient and oral
      metronidazole for the other. In both cases, magnetic resonance imaging (MRI) has
      proved to be essential for diagnostic. The primary source of infection remained
      unknown despite careful investigations.

PMID- 18714852
TI  - Eosinophilic fasciitis and toxic thyroid adenoma--a novel association.
AB  - Eosinophilic fasciitis is characterized by skin induration, peripheral blood
      eosinophilia, hypergammaglobulinaemia and thickening, fibrosis and inflammatory
      cell infiltration of the fascia. There have been several reports of illness
      particularly haematological disorders in patients with eosinophilic fasciitis.
      However, their association with thyroid disorders has rarely been described and
      includes autoimmune thyroiditis rather than toxic thyroid adenoma. We describe a
      case of a 53-year-old woman with simultaneous association of eosinophilic
      fasciitis and subclinical hyperthyroidism caused by toxic thyroid adenoma.
      Corticosteroids, antithyroid drugs and radioiodine therapy were started, with a
      good follow-up

PMID- 18714853
TI  - Gamma-hydroxybutyric acid (GHB) measurement by GC-MS in blood, urine and gastric
      contents, following an acute intoxication in Belgium.
AB  - Gamma-hydroxybutyrate (GHB, sodium oxybate) is a compound related to
      neuromodulator gamma-aminobutyric acid (GABA), emerging as a recreational drug of
      abuse and as a rape drug. GHB-related emergencies have dramatically increased in
      the 1990s, but a decrease is observed since 2000. We describe the case of an
      acute GHB intoxication in a 28-year-old male who fell unconscious after ingestion
      of a mouthful of an unknown beverage, and required medical support for 2 days. A
      cocaine abuse was also detected by preliminary toxicological screening, but the
      clinical presentation was not typical of cocaine intoxication. A simple liquid
      liquid extraction was used for quantitation of GHB, followed by disilyl
      derivatization and analysis in selective ion monitoring (SIM) mode by gas
      chromatography-mass spectrometry (GC-MS), using GHB-d6 as internal standard. High
      concentrations of GHB were detected in urine (3020 mg/L) and gastric contents
      (71487 mg/L) at admission. After a 6-hours delay, GHB was still present in urine
      at 2324 mg/L and in blood at 43 mg/L. The clinical symptoms of cocaine
      intoxication were diminished by GHB consumption, and the cerebral scan was
      modified. Attention must thus be paid to acute intoxications with surprising
      clinical symptoms, and GHB has probably to be added to the preliminary
      toxicological screening. Data available regarding GHB are briefly reviewed, and
      our results are compared with previously published reports of non-fatal GHB
      intoxication.

PMID- 18714854
TI  - Mismatch of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and
      Tc-99m pertechnetate thyroid scan in subacute thyroiditis.

PMID- 18714855
TI  - [Successive connections: juvenile idiopathic arthritis and systemic lupus
      erythematosus].

PMID- 18714856
TI  - Tires as habitats for mosquitoes: a review of studies within the eastern United
      States.
AB  - Discarded vehicle tires are a common habitat for a variety of container mosquito
      species. I reviewed the literature from the last 50 yr on mosquitoes collected
      within tires in the eastern United States with four objectives: to examine the
      historical and contemporary issues of tires as a habitat for mosquitoes, to
      identify tire-inhabiting species, to summarize findings from studies that focused
      on biotic and abiotic characteristics of tires, and to offer future directions to
      aid our understanding of tire-inhabiting mosquitoes. Thirty-two species have been
      documented, including seven invasives, with the most frequently encountered being
      Aedes triseriatus, Ae. albopictus, Ae. atropalpus, Culex restuans, Cx. pipiens,
      Cx. territans, Anopheles punctipennis, and Toxorhynchites rutilus. The proclivity
      of these species to occupy small containers is one possible explanation for their
      occurrence in tires. The native species Ae. triseriatus was abundant and the most
      often collected, particularly in central and northern regions, whereas the
      invasive Ae. albopictus was most abundant in the south. One half of the studies
      investigating aspects of the tire environment compared mosquito populations
      between sunlit and shaded tires, with the general finding that this factor alone
      led to dramatic differences in larval species composition and abundance patterns.
      Less frequently investigated factors, e.g., tire orientation, detritus, and
      proximity to humans, also were found to affect patterns of occupancy by
      mosquitoes. For the future, I suggest more surveys are needed in understudied
      areas, as well as quantitative experiments to determine habitat associations and
      community dynamics in tires, which are especially necessary to assist in
      understanding invasions. Discarded tires are important for studies of vector
      dynamics, because of their abundance near human populations and because they
      expand the habitat range of mosquitoes that vector pathogens.

PMID- 18714857
TI  - Morphology of the first instar of the house fly Musca domestica (Diptera:
      Muscidae).
AB  - Scanning electron microscopy documentation of the first instar of Musca domestica
      L. is presented for the first time. The following morphological structures are
      documented: antenna, maxillary palpus, facial mask, spinulation, posterior
      spiracles, anal pad, and integumental micropores. Morphology of the first-instar
      larva of M. domestica is discussed in light of existing knowledge about early
      larval instars of Calyptrata flies.

PMID- 18714858
TI  - Dispersal of Culex quinquefasciatus (Diptera: Culicidae) in a Hawaiian rain
      forest.
AB  - Introduced mosquito-borne pathogens avian malaria (Plasmodium relictum Grassi and
      Feletti) and avian pox virus (Avipoxvirus) have been implicated in the past
      extinctions and declines of Hawaiian avifauna and remain significant obstacles to
      the recovery and restoration of endemic Hawaiian birds. Effective management of
      avian disease will require extensive mosquito control efforts that are guided by
      the local ecology of the vector Culex quinquefasciatus Say (Diptera: Culicidae).
      During October and November 1997 and September through November 1998 five mark
      release-recapture experiments with laboratory-reared Cx. quinquefasciatus were
      conducted in a native rain forest on Hawaii Island. Of the overall 66,047
      fluorescent dye-marked and released females, 1,192 (1.8%) were recaptured in 43
      52 CO2-baited traps operated for 10-12-d trapping periods. Recaptured mosquitoes
      were trapped in all directions and at distances up to 3 km from the release site.
      The cumulative mean distance traveled (MDTs) over the trapping period ranged from
      a high of 1.89 km after 11 d (September 1998) to a low of 0.81 km after 11 d
      (November 1998). Released mosquitoes moved predominately in a downwind direction
      and they seemed to use forestry roads as dispersal corridors. Applying an
      estimated MDT of 1.6 km to a geographical information system-generated map of the
      Hakalau Forest National Wildlife Refuge clearly demonstrated that the effective
      refuge area could be reduced 60% by mosquitoes infiltrating into managed refuge
      lands. These findings should have significant implications for the design of
      future refuges and development of effective mosquito-borne avian disease control
      strategies.

PMID- 18714859
TI  - Sudden autumnal appearance of adult Culex tritaeniorhynchus (Diptera: Culicidae)
      at a park in urban Tokyo: first field evidence for prediapause migration.
AB  - During autumn, a large number of adult Culex tritaeniorhynchus Giles suddenly
      appeared at a park in urban Tokyo. A total of 14,069 females and 2,802 males were
      collected at rest by sweeping from April to November 2007, of which 99.8% of the
      females were collected from late September to November. The appearance of a large
      number of Cx. tritaeniorhynchus started on 22 September, peaked at 1,062 per
      collection/hr on 13 October, and gradually decreased by the end of November. A
      total of 565 females were marked and released on 3 October, and the total number
      of females in the park was estimated to be 545,225 +/- 157,392 by the Lincoln
      index. No females were collected by human landing collections, and the parous
      rate of females collected by sweeping was 4.4% (41/936). Dissections showed that
      85.7% (120/140) of these females were in reproductive diapause, with an ovariole
      stage of N or I and a primary over secondary follicular ratio < or = 1.5. From
      January to early April 2008, only 10 overwintering Cx. tritaeniorhynchus females
      were collected resting. These results indicated that these females were in
      reproductive diapause and that some overwintered in this urban setting. This is
      the first field evidence of prediapause seasonal migration of this species from
      breeding sites to overwintering sites.

PMID- 18714860
TI  - Impact of source reduction on the spatial distribution of larvae and pupae of
      Aedes albopictus (Diptera: Culicidae) in suburban neighborhoods of a Piedmont
      community in North Carolina.
AB  - Aedes albopictus (Skuse) is a principal nuisance mosquito species and a potential
      arbovirus vector throughout its geographic range in the United States. This
      species lays eggs, and progeny complete development in water-filled containers
      that are discarded in suburban landscapes. Source reduction of containers,
      achieved through environmental sanitation, was used to experimentally manipulate
      mosquito production to gain insight into the spatial structure of the population
      of immature Ae. albopictus. Our studies were conducted in suburban landscapes in
      Raleigh, NC, during the 2002 and 2003 mosquito seasons. Spatial analyses, using
      estimates of the mean and total standing crop of pupae and counts of the numbers
      of mosquito-positive containers, showed that the distribution of mosquito
      production was not spatially dependent on a neighborhood-wide basis. However, in
      all neighborhoods, mosquito production was clustered in at least one and often
      more than one adjacent residence. Point pattern analyses that considered only the
      presence or absence of pupae showed that pupae-positive residences were dispersed
      throughout neighborhoods receiving monthly source reduction treatments and
      clustered throughout control neighborhoods, indicating that source reduction
      affected the spatial distribution of pupae. Conversely, spatial analyses based on
      the presence or absence of larvae and pupae showed that mosquito production was
      randomly distributed among residences in both control and source reduction
      neighborhoods, showing that Ae. albopictus recolonized containers within several
      weeks after source reduction was implemented. Knowledge of the spatial
      distribution of production sites would allow management efforts for Ae.
      albopictus to be targeted to residences supporting high levels of mosquito
      production.

PMID- 18714861
TI  - Interspecific larval competition between Aedes albopictus and Aedes japonicus
      (Diptera: Culicidae) in northern Virginia.
AB  - Aedes albopictus (Skuse) and Aedes japonicus (Theobald) are two of the most
      recent and widespread invasive mosquito species to have become established in the
      United States. The two species co-occur in water-filled artificial containers,
      where crowding and limiting resources are likely to promote inter- or
      intraspecific larval competition. The performance of northern Virginia
      populations of Ae. japonicus and Ae. albopictus competing as larvae under field
      conditions was evaluated. Per capita rates of population increase for each
      species were estimated, and the effects of species composition and larval density
      were determined. In water-containing cups provided with oak leaves, Ae.
      albopictus larvae exhibited a competitive advantage over Ae. japonicus as a
      consequence of higher survivorship, shorter developmental time, and a
      significantly higher estimated population growth rate under conditions of
      interspecific competition. Intraspecific competition constrained population
      performance of Ae. albopictus significantly more than competition with Ae.
      japonicus. In the context of the Lotka-Volterra model of competition, these
      findings suggest competitive exclusion of Ae. japonicus in those habitats where
      this species co-occurs with Ae. albopictus.

PMID- 18714862
TI  - Effects of carbon dioxide, an octenol/phenol mixture, and their combination on
      tabanidae (Diptera) collections from French 2-tier box traps.
AB  - The French 2-tier box trap was evaluated in northwestern Florida to determine its
      attractiveness to host-seeking tabanids (Diptera) when baited with either CO2
      alone; a 4:1:8 mixture of octenol, 3-n-propylphenol, and 4-methylphenol; or a
      combination of CO2 plus 4:1:8 mixture. Six genera representing 43 species were
      obtained from this trap. Chrysops and Tabanus made up 10.3 and 87.4% of the
      total, respectively, with Chrysops celatus Pechuman and Tabanus pallidescens
      Philip as the predominate species from these two genera. CO2 alone and in
      combination with the octenol/phenol mixture enhanced overall tabanid collections
      three- to four-fold compared with no odor. Generally, more species were collected
      in the top tier of the French 2-tier trap regardless of treatment. Those species
      that showed a significant difference between top and bottom tiers in traps
      without odors continued this trend when traps were baited with the
      semiochemicals. However, Tabanus mixis Philip showed no tier preference in traps
      baited by CO2 alone, whereas Tabanus lineola F. showed no stratification
      difference with or without odors.

PMID- 18714864
TI  - Molecular evidence confirms the taxonomic separation of Lutzomyia tihuiliensis
      from Lutzomyia pia (Diptera: Psychodidae) and the usefulness of pleural
      pigmentation patterns in species identification.
AB  - The phlebotomine sand flies Lutzomyia pia (Fairchild & Hertig 1961) and Lutzomyia
      tihuiliensis Le Pont, Torrez-Espejo & Dujardin 1997 (Diptera: Psychodidae) belong
      to the pia series of the Lu. verrucarum species group, which includes several
      species that bite humans in Andean foci of leishmaniasis. The females of these
      two species exhibit isometry and isomorphism in anatomical structures of the head
      and terminalia commonly used in taxonomic identification of sand flies. They can
      only be differentiated based on subtle differences in the pigmentation of the
      pleura. In Lu. tihuiliensis, this is restricted to the basal portions of the
      katepimeron and katepisternum, whereas in Lu. pia both structures are totally
      pigmented. Taking into account the subtle morphological differences between these
      species, the objective of the current study was to evaluate the specific
      taxonomic status of Lu. tihuiliensis with respect to Lu. pia. A 475-bp portion of
      the mitochondrial genome was sequenced, composed of the 3' end of the cytochrome
      b gene, intergenic spacer 1, the transfer RNA gene for serine, intergenic spacer
      2, and the 3' end of the gene NAD dehydrogenase 1. Genetic analysis confirms that
      Lu. tihuiliensis and Lu. pia constitute two distinct species and this is
      supported by four strong lines of evidence, i.e., the paired genetic distances,
      size differences and amino acid composition of the cytochrome b protein, presence
      and absence of intergenic spacer one and divergence observed in the sequence of
      the transfer RNA gene for serine. It also confirms the validity of the pleural
      pigmentation pattern as a species diagnostic character and the importance of
      performing a detailed examination of this character during morphological
      determination of phlebotomine sand flies in the series pia.

PMID- 18714863
TI  - Assessment of alternative mating strategies in Anopheles gambiae: Does mating
      occur indoors?
AB  - Mating in Anopheles gambiae has been observed only in outdoor swarms. Here we
      evaluate whether mating also occurs indoors. Mark-release-recapture of virgin
      males and females in natural houses showed that mating occurred over a single day
      even when mosquitoes can leave the house through exit traps and without
      adaptation to laboratory conditions. In these experiments, insemination rate in
      the M molecular form of An. gambiae (and An. arabiensis) was higher than that of
      the S form (15 versus 6%). Under these conditions, smaller females of the M form
      mated more frequently than larger females of that form. Sampling mosquitoes
      throughout the day showed that both sexes enter houses around sunrise and leave
      around sunset, staying indoors together from dawn to dusk. In an area dominated
      by the M form, the daily rate of insemination in samples from exit traps was
      approximately 5% higher than in those from entry traps, implying that mating
      occurred indoors. Importantly, frequency of cross mating between the molecular
      forms was as high as that between members of the same form, indicating that,
      indoors, assortative mating breaks down. Altogether, these results suggest that
      indoor mating is an alternative mating strategy of the M molecular form of An.
      gambiae. Because naturally occurring mating couples have not yet been observed
      indoors, this conclusion awaits validation.

PMID- 18714865
TI  - Phenotypic diversity of Triatoma infestans at the microgeographic level in the
      Gran Chaco of Argentina and the Andean valleys of Bolivia.
AB  - Triatoma infestans (Klug) is the main vector of Trypanosoma cruzi, etiologic
      agent of Chagas disease. The phenotype of the species varies at different
      geographic scales. The objective of this study was to compare the antennal
      phenotype of spatially close T. infestans populations and to evaluate its
      usefulness as a marker of exchange of individuals between populations. The
      antennal phenotype of 190 T. infestans from Argentina and Bolivia was analyzed
      using uni- and multivariate techniques. This study shows heterogeneity of the
      antennal phenotypes of closely related T. infestans populations living in
      different habitats. Specimens collected in a goat corral and a rabbit cage in La
      Rioja (Argentina) were dissimilar to the specimens collected in the nearby
      intradomestic environment. Similarly, specimens from peridomestic corrals in
      Cochabamba (Bolivia) were different from the intradomestic and sylvatic
      specimens, indicating some degree of isolation between these populations. In
      contrast, T. infestans collected in chicken coops and the intradomestic
      environment were similar, in all studied regions, suggesting a frequent exchange
      of individuals between the two habitats and/or because of the similarity of the
      habitat due to the presence of chickens in the intradomestic environment. We
      propose that each habitat affects in a particular mode the insect morphology and
      these changes could be used to identify recolonizing T. infestans. These results
      support the hypothesis of different degrees of isolation between intradomestic
      and peridomestic habitats. Within this context, special attention should be given
      to chicken coops and other close peridomestic structures in relation to the
      recolonization process of domestic habitats by T. infestans.

PMID- 18714866
TI  - The mitochondrial control region of blowflies (Diptera: Calliphoridae): a hot
      spot for mitochondrial genome rearrangements.
AB  - The family Calliphoridae consists of myiasis-causing flies, including species of
      economic, forensic, and medical importance. In this study, the complete control
      regions (CRs) of mitochondrial DNA from 15 calliphorid species were sequenced and
      structurally characterized. The CRs had a high content of adenines (A) and
      thymines (T) and varied in length from 854 to 2,018 bp, showing intraspecific
      variations in sequence and length. Two major domains were identified: the
      conserved domain containing conserved sequence blocks and cis-regulatory
      structures that may be related to the transcription and the origin of replication
      of mitochondrial DNA, and the variable domain, containing high sequence and
      length variation. Within the variable domain, duplication of the tRNA(Ile) gene,
      previously reported for three Chrysomya species, was identified in two more
      species of this genus and in two species of two other genera. The structural
      characterization shows the plasticity of the mitochondrial genome in dipterans.
      The organizational similarities of the duplicated region found in different
      species and the possible origin of the duplicated genes are discussed.

PMID- 18714867
TI  - Gene structure and expression of a pyrethroid-metabolizing esterase, CzEst9, from
      a pyrethroid resistant Mexican population of Rhipicephalus (Boophilus) microplus
      (Acari: Ixodidae).
AB  - A population of Rhipicephalus (Boophilus) microplus (Canestrini) (Acari:
      Ixodidae), designated Coatzacoalcos, sampled from a ranch near Veracruz, Mexico,
      was found to possess a high level of resistance to pyrethroid-based acaricides.
      Bioassay and biochemical and molecular analysis had previously shown that
      resistance in this population could primarily be attributed to expression of a
      highly active metabolic esterase designated CzEST9. We cloned and sequenced the
      entire CzEST9 coding region, including introns and > 1.0 kb upstream from the
      transcription start site, and we compared the upstream region sequence between
      individual resistant and susceptible ticks from several populations with
      different pyrethroid resistance characteristics. In the 1.0-kb upstream region
      sequence, four variant nucleotides were found, and a TGA trinucleotide occurred
      as either four, five, or nine tandem repeats. However, none of these promoter
      region sequence differences could be clearly associated with a pyrethroid
      resistant phenotype; thus, we concluded that differences in gene promoter
      sequence were not responsible for the pyrethroid resistance mechanism in the Cz
      strain. CzEST9 was expressed in recombinant Escherichia coli and Pichia pastoris
      systems and esterase activity was obtained in recombinant CzEST9 from the P.
      pastoris system.

PMID- 18714868
TI  - Expressed cDNAS from embryonic and larval stages of the horn fly (Diptera:
      Muscidae).
AB  - We used an expressed sequence tag approach to initiate a study of the genome of
      the horn fly, Hematobia irritans (L.) (Diptera: Muscidae). Two normalized cDNA
      libraries were synthesized from RNA isolated from embryos and first instars from
      a field population of horn flies. Approximately 10,000 clones were sequenced from
      both the 5' and 3' directions. Sequence data from each library was assembled into
      a database of tentative consensus sequences (TCs) and singletons and used to
      search public protein databases and annotate the sequences. Additionally, the
      sequences from both the egg and larval libraries were combined into a single
      database consisting of 16,702 expressed sequence tags (ESTs) assembling into 2886
      TCs and 1,522 singleton entries. Several sequences were identified that may have
      roles in the horn fly's resistance to insecticides. The availability of this
      database will facilitate the design of microarray and other experiments to study
      horn fly gene expression on a larger scale than previously possible. This would
      include studies designed to investigate metabolic-based insecticide resistance,
      identify novel antigens for vaccine-based control approaches, and discover new
      proteins to serve as targets for new pesticide development.

PMID- 18714869
TI  - Evidence of pyrethroid resistance in eggs of Pediculus humanus capitis
      (Phthiraptera: Pediculidae) from Argentina.
AB  - Insecticide resistance in Pediculus humanus capitis De Geer 1778 (Phthiraptera:
      Pediculidae) from different countries has been well documented in the last years.
      Otherwise, little research has been reported about insecticide resistance in
      insect embryos and none in human louse embryos. In this work, we studied
      insecticide resistance in eggs of three head lice populations whose pyrethroid
      resistance was shown in adults and nymphs compared with a susceptible laboratory
      body louse strain. All head louse populations showed high permethrin resistance
      in eggs. Levels of permethrin resistance (LCRs) assessed in eggs by immersion
      technique were higher than those previously reported for the corresponding
      populations of adults by topical application. Comparison of LCR values for
      different populations showed that there was a direct relationship between the
      resistance levels assessed in eggs and those in adults. All permethrin-resistant
      eggs showed high resistance to d-phenothrin and dichloro-diphenyl-trichloroethane
      (DDT) and low resistance to carbaryl, which is in common with the resistance
      profile established for adults and nymphs. The results concerning the high
      resistance to pyrethroid (permethrin and d-phenothrin) and the cross-resistance
      to DDT and carbaryl detected in head louse eggs and adults suggested similar
      resistance mechanisms in eggs and adults of head louse populations from adults.

PMID- 18714870
TI  - Mating competitiveness of male Anopheles arabiensis mosquitoes irradiated with a
      partially or fully sterilizing dose in small and large laboratory cages.
AB  - Male mating competitiveness is a crucial parameter in many genetic control
      programs including the sterile insect technique (SIT). We evaluated
      competitiveness of male Anopheles arabiensis Patton as a function of three
      experimental variables: (1) small or large cages for mating, (2) the effects of
      either a partially sterilizing (70 Gy) or fully sterilizing (120 Gy) dose, and
      (3) pupal or adult irradiation. Irradiated males competed for females with an
      equal number of unirradiated males. Competitiveness was determined by measuring
      hatch rates of individually laid egg batches. In small cages, pupal irradiation
      with the high dose resulted in the lowest competitiveness, whereas adult
      irradiation with the low dose gave the highest, with the latter males being equal
      in competitiveness to unirradiated males. In the large cage, reduced
      competitiveness of males irradiated in the pupal stage was more pronounced
      compared with the small cage; the males irradiated as adults at both doses
      performed similarly to unirradiated males. Unexpectedly, males irradiated with
      the high dose performed better in a large cage than in a small one. A high
      proportion of intermediate hatch rates was observed for eggs collected in the
      large cage experiments with males irradiated at the pupal stage. It is concluded
      that irradiation of adult An. arabiensis with the partially sterilizing dose
      results in the highest competitiveness for both cage designs. Cage size affected
      competitiveness for some treatments; therefore, competitiveness determined in
      laboratory experiments must be confirmed by releases into simulated field
      conditions. The protocols described are readily transferable to evaluate male
      competitiveness for other genetic control techniques.

PMID- 18714871
TI  - Prolonged efficacy of IR3535 repellents against mosquitoes and blacklegged ticks
      in North America.
AB  - Here I report the first findings of consistently high, long-duration efficacy of
      IR3535 (ethyl butyl acetyl aminopropionate) formulations in the United States. I
      tested novel, controlled-release formulations of IR3535, at 10% in lotion and at
      20% in pump spray and aerosol, against mosquitoes in the field and blacklegged
      ticks in the laboratory. These were also the first studies to be conducted under
      the authority of the U.S. Environmental Protection Agency's Human Studies Rule of
      2006, and the protocols underwent science and ethics reviews by five entities.
      IR3535 is better known in Europe than in North America, having been marketed in
      the United States only more recently, and there are comparatively few
      publications on its efficacy. I began with pretrial studies of dosing behavior to
      compute formula-specific mean dosing rates for the subsequent efficacy trials.
      Dosing rates were lower than the 1 ml/600 cm rate commonly used to quantify
      efficacy. Complete protection times ranged from 7.1 to 10.3 h for mosquitoes and
      from 9.1 to 12.2 h for blacklegged ticks. Long protection duration resulted in
      many cases being truncated by darkness or eventual subject withdrawal, which
      suggests that actual protection times were probably greater.

PMID- 18714872
TI  - Toxicity of oxalic acid against adult Hyalomma lusitanicum ticks (Ixodida:
      Ixodidae) in laboratory conditions: LD50.
AB  - The abundance of Hyalomma lusitanicum ticks in open areas of central Spain is the
      result of many natural and human factors. Control of tick populations by chemical
      and other means may be necessary until we can determine the key global factors in
      this important tick population. Despite many attempts to establish ecological
      control of ticks, there is little data about the activity of organic acids. This
      article describes tests on the in vitro toxicity of oxalic acid (OA) against wild
      H. lusitanicum adult ticks. Serial dilutions of OA dihydrate were prepared in
      distilled water with 1% of Tween 20. The treatment was applied in three
      replicates of 10-14 tick/dose from 0 to 1.037 mg OA/tick. Doses > 0.311 mg of OA
      killed all ticks in 24 h. Toxicity of the OA increased over time; therefore, the
      LD50 decreased from 0.22 mg at 24 h to 0.127 mg at 72 h. The results obtained
      show the toxicity of OA against adult H. lusitanicum ticks under in vitro
      conditions. Comparing toxicity in ticks and honey bees, OA seems a relatively
      safe treatment for nontarget arthropods and a potential alternative for tick
      population control. However, further research is needed to establish its real
      effectiveness and applicability under field conditions.

PMID- 18714874
TI  - First detection of Leishmania infantum in Phlebotomus (Larroussius) major
      (Diptera: Psychodidae) from Iran.
AB  - Ghir-Karzin district is one of the most important endemic foci of visceral
      leishmaniaisis (VL) in Fars province of southern Iran. To identify the vector(s)
      of Leishmania in this focus, a total of 2,539 sand flies were collected during
      June to September 2005. Eleven species (six Phlebotomus and five Sergentomyia)
      were identified, of which Phlebotomus papatasi Scopoli and Phlebotomus major
      Annandale were the first (37.4%) and third (11.2%) most common species,
      respectively. Natural leptomonad infections were observed in two P. papatasi
      (4.25%) and three P. major (6.65%) specimens on dissection and microscopic
      examination. Using a Leishmania genus-specific standard polymerase chain reaction
      (PCR; primers RV1-RV2) and a species-specific nested-PCR (primers LINR4, LIN17,
      and LIN 19), Leishmania infantum and Leishmania major kinetoplast minicircle DNA
      was detected in 6 of 72 P. major (8.3%) and 4 of 65 P. papatasi (6.1%),
      respectively. This is the first detection of L. infantum in P. major, implicating
      this sand fly as a probable vector of VL in Iran.

PMID- 18714873
TI  - Susceptibility of Peruvian mosquitoes to eastern equine encephalitis virus.
AB  - Mosquitoes were collected in the Amazon Basin, near Iquitos, Peru, and used in
      experimental studies to evaluate their susceptibility to strains of eastern
      equine encephalitis virus (EEEV) that were isolated from mosquitoes captured
      within 20 km of Iquitos. When fed on hamsters or chickens with a viremia of 4105
      plaque-forming units (PFU) of EEEV/ml, Culex pedroi Sirivanakarn and Belkin,
      Aedesfulvus (Wiedemann), Psorophora albigenu (Peryassu), and Psorophoraferox (Von
      Humboldt) were susceptible to infection, whereas none of the Aedes serratus
      (Theobald), Culex vomerifer Komp, Culex gnomatos Sallum, Huchings, and Ferreira,
      Culex portesi Senevet and Abonnenc, or Culex coronator Dyar and Knab became
      infected, even though they fed on the same viremic blood sources. When these
      mosquito species fed on animals with viremias of approximately 10(8) PFU/ml, Cx.
      pedroi, Ae.II (Brazil-Peru) and a lineage III (Argentina-Panama) isolate of EEEV.
      This study, combined with the repeated isolation of strains of EEEV from Cx.
      pedroi captured in the Amazon Basin region of Peru, suggests that Cx. pedroi may
      be the primary enzootic vector of EEEV in this region.

PMID- 18714875
TI  - Transmission dynamics of Borrelia burgdorferi s.s. during the key third day of
      feeding by nymphal Ixodes scapularis (Acari: Ixodidae).
AB  - Nymphal Ixodes scapularis Say are the principal vectors of Lyme disease
      spirochetes (Borrelia burgdorferi sensu stricto) in the eastern United States.
      Physicians frequently face the decision of whether or not to administer
      prophylactic antibiotics to human tick bite victims in Lyme disease endemic
      regions, based on the overall probability that such bites will result in
      infection with B. burgdorferi s.s. We evaluated the transmission dynamics of B.
      burgdorferi s.s. during the key third day of nymphal I. scapularis feeding, when
      the risk of transmission rapidly increases. The cumulative probability that 50%
      of infected ticks transmitted B. burgdorferi s.s. occurred at 68 h of tick
      attachment and our overall estimate that a human tick bite would result in
      transmission of B. burgdorferi s.s. was 2.4%.

PMID- 18714876
TI  - Vector competence of three Australian mosquitoes, Verrallina carmenti,
      Verraullina lineata, and Mansonia septempunctata (Diptera: Culicidae), for Ross
      River virus.
AB  - The vector competence of Verrallina carmenti (Edwards), Verrallina lineata
      (Taylor), and Mansonia septempunctata (Theobald) (Diptera: Culicidae) from north
      Queensland, Australia, was tested using two isolates of Ross River virus (family
      Togaviridae, genus Alphavirus, RRV). All three species were tested using RRV
      isolate RR102MP (ex-Cairns, Queensland, Australia), whereas Ve. carmenti and Ve.
      lineata also were tested using RR2186 (ex-Bourke, New South Wales, Australia).
      Transmission was tested using the capillary tube method, with infection of
      mosquito bodies and saliva determined using cell culture. Infection with RR102MP
      resulted in 27.5% of Ve. carmenti, 19.2% of Ve. lineata and 13.3% of Ma.
      septempunctata transmitting virus. When Ve. carmenti and Ve. lineata were
      infected with RR2186, transmission rates for both species were generally < 10%,
      although a transmission rate of 25% was recorded for Ve. lineata exposed to high
      titer virus. These results indicated that the three mosquito species have the
      potential to contribute to local transmission cycles.

PMID- 18714877
TI  - Molecular detection of spotted fever group Rickettsia in Dermacentor silvarum
      from a forest area of northeastern China.
AB  - In total, 676 Dermacentor silvarum Olenev (Acari: Ixodidae) from a forest area of
      Jilin Province in northeastern China were examined by polymerase chain reaction
      for the presence of spotted fever group (SFG) Rickettsia. The overall positive
      rate was 10.7%, with a 95% confidence interval from 8.3 to 13.0%. The SFG
      Rickettsia infection was more prevalent in adults than in nymphs, and in fed
      ticks obtained from domestic animals than in those collected on vegetation.
      Sequence analysis of the partial outer membrane protein A gene confirmed the
      existence of R. sibirica and discovered a novel rickettsial agent in this area,
      the sequence of which was identical to that of DnS14 genotype Rickettsia
      previously reported in the former Soviet Union.

PMID- 18714878
TI  - Detection of a spotted fever group Rickettsia in the tick Ixodes tasmani
      collected from koalas in Port Macquarie, Australia.
AB  - Four species of Rickettsia are recognized as endemic to Australia. This study
      reports the detection of a new spotted fever group Rickettsia in the common
      marsupial tick Ixodes tasmani Neumann collected from koalas (Phascolarctos
      cinereus) in Port Macquarie, NSW, Australia. Based on the results of polymerase
      chain reaction (PCR) amplification of extracted tick DNA with primers targeting
      the citrate synthase gene (gltA) and the outer membrane proteins A and B (ompA.
      ompB), Rickettsiae were detected in 22 of 78 I. tasmani tick samples (28.2%).
      Sequence data obtained for the three genes displayed the closest degree of
      similarity to Rickettsia heilongjiangiensiss for gltA (99.4%; 331/333 bp),
      Rickettsia amblyommii for the ompA gene (94.8%; 417/440 bp), and both Rickettsia
      massiliae and Rickettsia rhipicephali for the ompB gene (97%; 770/803 bp). BLAST
      and phylogenetic analysis of partial sequences obtained for the three genes were
      found to have sufficient nucleotide variation from the current recognized
      Australian species to be considered a distinct spotted fever group Rickettsia.

PMID- 18714879
TI  - Impact of aerial spraying of pyrethrin insecticide on Culex pipiens and Culex
      tarsalis (Diptera: Culicidae) abundance and West Nile virus infection rates in an
      urban/suburban area of Sacramento County, California.
AB  - In response to an epidemic amplification of West Nile virus (family Flaviviridae,
      genus Flavivirus, WNV), the Sacramento and Yolo Mosquito and Vector Control
      District (SYMVCD) sprayed ultralow-volume (ULV) formulations of pyrethrin
      insecticide (Evergreen EC 60-6: 6% pyrethrin insecticide, 60% piperonylbutoxide;
      MGK, Minneapolis, MN, applied as 0.003 kg/ha [0.0025 lb/acre] ) over 218 km2 in
      north Sacramento and 243.5 km2 in south Sacramento on three consecutive evenings
      in August 2005. We evaluated the impact of this intervention in north Sacramento
      on the abundance and WNV infection rates of Culex pipiens L. and Culex tarsalis
      Coquillett. Mortality rates of caged Cx. tarsalis sentinels ranged from 0% under
      dense canopy to 100% in open fields. A comparison of weekly geometric mean
      mosquito abundance in CO2-baited traps in sprayed and unsprayed areas before and
      after treatment indicated a 75.0 and 48.7% reduction in the abundance of Cx.
      pipiens and Cx. tarsalis, respectively. This reduction was statistically
      significant for Cx. pipiens, the primary vector of WNV, with highest abundance in
      this urban area, but not for Cx. tarsalis, which is more associated with rural
      areas. The infection rates of WNV in Cx. pipiens and Cx. tarsalis collected from
      the spray zone were 8.2 and 4.3 per 1,000 female mosquitoes in the 2 wk before
      and the 2 wk after applications of insecticide, respectively. In comparison, WNV
      infection rates in Cx. pipiens and Cx. tarsalis collected at same time interval
      in the unsprayed zone were 2.0 and 8.7 per 1,000, respectively. Based on the
      reduction in vector abundance and its effects on number of infective bites
      received by human population, we concluded that the aerial application
      ofpyrethrin insecticide reduced the transmission intensity of WNV and decreased
      the risk of human infection.

PMID- 18714880
TI  - Utilization of domestic and natural containers by Aedes oceanicus in American
      Samoa.
AB  - Larval and pupal surveys of 439 natural and 2,455 domestic containers (total of
      2,894 containers) were undertaken in four villages in American Samoa during the
      wet and dry seasons. For the first time, larvae and pupae of Ae. oceanicus were
      found in a variety of domestic containers (including buckets, plastic and
      polystyrene containers, cans, and tires) in addition to their traditionally
      reported habitats of plant leaf axils. Finding Ae. oceanicus in artificial
      containers in three villages during both the wet and dry seasons suggests that
      Ae. oceanicus is adapting to use these increasingly abundant water sources for
      breeding sites. The larger water volumes held by such containers could ensure the
      survival of this species during prolonged dry weather periods.

PMID- 18714881
TI  - Evaluation of squirrels (Rodentia: Sciuridae) as ecologically significant hosts
      for Anaplasma phagocytophilum in California.
AB  - Granulocytic anaplasmosis (GA), caused by Anaplasma phagocytophilum, is a
      potentially fatal, emerging rickettsial disease of humans, domestic animals, and
      wildlife. The purpose of this study was to determine whether sciurids from
      multiple areas of northern California were infested with ticks or exposed to or
      infected with A. phagocytophilum using polymerase chain reaction (PCR) and
      indirect-fluorescent antibody (IFA) serology. Sciurids of nine different tree-
      and ground-dwelling species were assessed: arboreal squirrels (western and
      eastern gray squirrels, Sciurus griseus and S. carolinensis, and Douglas
      squirrels, Tamiasciurus douglasii) but not northern flying squirrels (Glaucomys
      sabrinus) had greater evidence of exposure and current infection than did
      semiarboreal or ground dwelling sciurids (California ground squirrels,
      Spermophilus beecheyi, and chipmunks, Tamias spp.). Western gray squirrels had
      the most extensive exposure (70.7% seroprevalence and 12.1% PCR prevalence).
      Positive squirrels were identified in all regions where squirrels were collected.
      A logistic regression identified being a western gray squirrel (OR = 20.5, P =
      2.95 X 10(-8)) and from the north coastal region of California (OR = 9.052, P =
      1.41 X 10(-6)) as having the highest risk of exposure to A. phagocytophilum. Five
      of nine sciurid species had evidence of infestation with Ixodes pacificus or I.
      spinipalpis that could vector A. phagocytophilum. Extensive exposure from
      multiple areas suggests sciurids may be important in the maintenance of GA in
      California and indicates that studies of reservoir competence of these species
      are warranted.

PMID- 18714882
TI  - Ticks (Acari: Ixodidae) infesting wild birds in an Atlantic forest area in the
      state of Sao Paulo, Brazil, with isolation of rickettsia from the tick Amblyomma
      longirostre.
AB  - During field work in Nazare Paulista, state of Sao Paulo, Brazil, we found 13
      (56.5%) of 23 birds (mostly Passeriformes) to be infested by 28 larvae and 1
      nymph of Amblyomma spp. Two larvae were reared to the adult stage, being
      taxonomically identified as Amblyomma parkeri Fonseca and Aragio, whereas five
      larvae and one nymph were identified as Amblyomma longirostre Koch. All six A.
      longirostre specimens were shown to be infected by rickettsia, as demonstrated by
      polymerase chain reaction (PCR) targeting two rickettsial genes (gltA and ompA)
      or isolation of rickettsia in cell culture from one of the ticks. This isolate
      was designated as strain AL, which was established in Vero cell culture and was
      molecularly characterized by DNA sequencing fragments of the rickettsial genes
      gltA, htrA, ompA, and ompB. Phylogenetic analyses inferred from ompA and ompB
      partial sequences showed a high degree of similarity of strain AL with Rickettsia
      sp. strain ARANHA, previously detected by PCR in A. longirostre ticks from
      Rondonia, northern Brazil. We conclude that strain AL is a new rickettsia
      genotype belonging to the same species of strain ARANHA, which are closely
      related to Candidatus 'R. amblyommii'. Further studies should elucidate if
      strains AL and ARANHA are different strains of Candidatus 'R. amblyommii' or are
      a new species.

PMID- 18714883
TI  - A web-based relational database for monitoring and analyzing mosquito population
      dynamics.
AB  - Mosquito population dynamics have been monitored on an annual basis in the state
      of Iowa since 1969. The primary goal of this project was to integrate light trap
      data from these efforts into a centralized back-end database and interactive
      website that is available through the internet at http://iowa
      mosquito.ent.iastate.edu. For comparative purposes, all data were categorized
      according to the week of the year and normalized according to the number of traps
      running. Users can readily view current, weekly mosquito abundance compared with
      data from previous years. Additional interactive capabilities facilitate analyses
      of the data based on mosquito species, distribution, or a time frame of interest.
      All data can be viewed in graphical and tabular format and can be downloaded to a
      comma separated value (CSV) file for import into a spreadsheet or more
      specialized statistical software package. Having this long-term dataset in a
      centralized database/website is useful for informing mosquito and mosquito-borne
      disease control and for exploring the ecology of the species represented therein.
      In addition to mosquito population dynamics, this database is available as a
      standardized platform that could be modified and applied to a multitude of
      projects that involve repeated collection of observational data. The development
      and implementation of this tool provides capacity for the user to mine data from
      standard spreadsheets into a relational database and then view and query the data
      in an interactive website.

PMID- 18714884
TI  - Larval competition of Chrysomya megacephala and Chrysomya rufifacies (Diptera:
      Calliphoridae): behavior and ecological studies of two blow fly species of
      forensic significance.
AB  - Chrysomya megacephala and Chrysomya rufifacies are two predominant necrophagous
      species in Taiwan. Larvae of the latter can prey on other maggots, including that
      of their own species as facultative food. This facultative characteristic of C.
      rufifacies may enhance its competitive advantage over other maggots and could
      also change the situation of other coexisting colonies. In this study, these two
      species were colonized in the laboratory, and the main objective was to try to
      understand the effect of competition on larval development. According to our
      results, intraspecific competition mostly occurred as competition for food; when
      the rearing density was increased, larvae pupated earlier, resulting in a lighter
      adult dry weight. The tendencies were similar in both species, but C. megacephala
      developed smaller viable adults and had higher survivorship at high densities.
      Although C. rufifacies could use the food resource of cannibalism, its
      survivorship was still low. Our results also showed there were significant
      interactions between intraspecific competition and the density factor. However,
      with interspecific competition, the first-instar larvae of C. rufifacies invaded
      maggot masses of C. megacephala to feed together. The third instars of C.
      rufifacies were able to expel C. megacephala larvae from food by using a fleshy
      protrusion on their body surface; C. megacephala was usually forced to pupate
      earlier by shortening its larval stages. The results indicated that a temporary
      competitive advantage could only be obtained by C. rufifacies under a proper
      larval density. In addition, the effects on different larval stages, the
      responses to different competition intensities, and the temperature-dependent
      effects on interspecific competition are also discussed. In general, under mixed
      species rearing at different temperatures and densities, larval duration, adult
      dry weight, and survivorship of both species decreased. However, our results did
      not completely agree with previous studies, and we suspect that the difference
      was partially caused by different experimental designs and different biological
      characters of different blow fly colonies. Our results also suggest that both the
      predation ability and defense or escape activity should be taken into account
      when evaluating larval competitive advantages. The durations of larval stages of
      these two species could be decreased by approximately 54 h when a single species
      was reared alone and food was limited; the largest reduction in larval duration,
      approximately 25 h in C. megacephala and 34 h in C. rufifacies, caused by
      interspecific competition was under a high larval density. In conclusion,
      competition decreased the larval duration of these two species by up to 2 d; this
      also draws attention to justifying the postmortem interval estimation of using
      larval developmental data when larval competition exists.

PMID- 18714885
TI  - Mosquito species richness, composition, and abundance along habitat-climate
      elevation gradients in the northern Colorado Front Range.
AB  - We exploited elevation gradients (1,500-2,400 m) ranging from plains to montane
      areas along the Poudre River and Big Thompson River in the northern Colorado
      Front Range to determine how mosquito species richness, composition, and
      abundance change along natural habitat-climate-elevation gradients. Mosquito
      collections in 26 sites in 2006 by using CO2-baited CDC light traps yielded a
      total of 7,136 identifiable mosquitoes of 27 species. Commonly collected species
      included Aedes vexans (Meigen) (n = 4,722), Culex tarsalis Coquillett (n = 825),
      Ochlerotatus increpitus (Dyar) (n = 546), Ochlerotatus trivittatus (Coquillett)
      (n = 303), Aedes cinereus Meigen (n = 280), Ochlerotatus melanimon (Dyar) (n =
      146), Ochlerotatus dorsalis (Meigen) (n = 67), Culiseta inornata (Williston) (n =
      52), Ochlerotatus pullatus (Coquillett) (n = 38), Ochlerotatus spencerii
      idahoensis (Theobald) (n = 37), and Culex pipiens L. (n = 29). Species richness
      was highest in plains habitats at elevations below 1,600 m. Numerous species were
      found exclusively or predominantly at low elevations below 1,700 m [Anopheles
      earlei Vargas, Anophelesfreeborni Aitken, Coquilletidia perturbans (Walker),
      Culex erythrothorax (Dyar), Cx. pipiens, Culex territans Walker, Oc. dorsalis,
      Ochlerotatus hendersoni (Cockerell), Oc. melanimon, and Oc. trivittatus], whereas
      others occurred predominantly at high elevations above 2,300 m [Ae. cinereus,
      Culiseta incidens (Thomson), Culiseta morsitans (Theoblad), Ochlerotatus
      cataphylla (Dyar), Ochlerotatus intrudens (Dyar), Oc. pullatus, and Ochlerotatus
      punctor (Kirby)]. Ae. vexans and Cx. tarsalis were abundant in the plains (<
      1,600 m; mean June-August temperature > 19.5 degrees C), occurred at low
      abundances in foothills and low montane areas (1,610-1,730 m; 18.0-19.5 degrees
      C), and they were collected only sporadically in montane areas above 1,750 m
      (mean June-August temperature < 17.5 degrees C). These findings suggest that
      future climate warming may lead to shifts in distribution patterns of West Nile
      virus vectors (e.g., Cx. tarsalis) toward higher elevations in Colorado.

PMID- 18714886
TI  - Enhancement of risk of tick-borne infection: environmental and parasitological
      aspects of the problem.
AB  - The appearance of phenotypic (and probably genetic) exoskeleton anomalies in
      Ixodes ticks, first discovered and described elsewhere, seems to be a global
      phenomenon clearly related to environment pollution by heavy metal ions. These
      external markers of cadmium accumulation in the tick indicate an enhanced risk of
      tick-borne infection related to an increased vectorial capacity. This manifests
      itself in the ability of infected ticks both to quest longer and to show
      increased locomotory activity (hunting) compared with normal ticks. Ticks with
      exoskeleton anomalies show a greater susceptibility to different microorganisms,
      including tick-borne pathogens, and more intense pathogen replication with a
      higher prevalence of multi-infection.

PMID- 18714887
TI  - 50th anniversary of the American Journal of Clinical Hypnosis.

PMID- 18714889
TI  - What we can do with hypnosis: a brief note.
AB  - This article summarizes the search for efficacious hypnotic treatments. Eighteen
      major meta analyses were reviewed and the results evaluated using the criteria of
      Chambless & Hollon, (1998). The analysis identified 32 disorders for which
      hypnosis can be considered a possible treatment, 5 for which it seems effective,
      and 2 for which it appears specific. If clinicians use hypnosis in the situations
      where it seems to be efficacious, and systematically expand the list of
      conditions where it will be helpful, the results will be even more impressive for
      the 100th anniversary of this Journal.

PMID- 18714888
TI  - 50 years of hypnosis in medicine and clinical health psychology: a synthesis of
      cultural crosscurrents.
AB  - In 2008, the 50th anniversary of ASCH, hypnosis is used increasingly for
      healthcare applications in hospitals, clinics, and psychotherapy practice. A
      substantial body of research demonstrates the efficacy of hypnosis as part of the
      integrative treatment of many conditions that traditional medicine has found
      difficult to treat (e.g., Pinnell & Covino, 2000; Elkins, Jensen, & Patterson,
      2007). The practice of hypnosis in healthcare has been altered and centrally
      influenced by the rapid growth of technological medicine in the 1950's, the AIDS
      epidemic and development of psychoneuroimmunology, revolutionary developments in
      genetics and neuroimaging technology, and the progression from alternative to
      integrative medicine. We have come to develop more detailed expectations about
      the beneficial effects of hypnotic interventions for health problems. We have
      also come to know that in these populations hypnosis can lead not only to reduced
      anxiety but also specifically altered physiological parameters.

PMID- 18714890
TI  - The early days: remembering William S. Kroger, M.D.

PMID- 18714891
TI  - The (dramatic) process of psychotherapy.
AB  - Psychotherapy can be conceived as a symbolic drama in which patients can
      experientially realize their capacity to change. Methods derived from hypnosis
      can empower therapy without the use of formal trance. A case conducted by Milton
      Erickson is presented and deconstructed in order to illuminate Erickson's
      therapeutic patterns. A model is offered for adding drama to therapy, and the
      model is placed into a larger model of choice points in psychotherapy.

PMID- 18714892
TI  - Hypnosis, hypnotizability and treatment.
AB  - There is broad agreement that a phenomenon we call "hypnosis" exists. However,
      there is no generally accepted definition of hypnosis. A brief historical
      overview of the use of hypnosis in healing practices demonstrates how it evolved
      willy-nilly, and like Topsy, "just growed" into its current status in medicine,
      psychiatry, psychology and dentistry. The mechanisms underlying hypnosis and how
      hypnosis differs from other cognitive states are almost totally unknown. With the
      exceptions of suggestions for pain control, current concepts of high, medium, low
      or non-hypnotizability do not reliably predict clinical outcomes for most
      medical, psychiatric or dental disorders. We do know that it is relatively easy
      to reliably evaluate hypnotizability, but other than choosing volunteers or
      subjects who will or will not exhibit traditional hypnotic phenomena, we rarely
      know what to do with that evaluation with actual clinical patients. Four case
      studies, representative of many others, chosen retrospectively from a practice
      that spans 45 years, illustrate how traditional or modern hypnotizability
      assessment is irrelevant in the clinical setting. Although the four patients
      differed obviously and vastly in hypnotizability, they all benefited from the use
      of hypnosis.

PMID- 18714893
TI  - Death and hypnosis: two remarkable cases.
AB  - The Journal of the American Medical Association reported The First Recorded Death
      in Hypnosis in its issue of October 27, 1894. Ninety-nine years later, on
      September 23, 1993 a healthy 24-year old mother of two was found dead at home,
      fully clothed and draped across the foot of one of her children's bed, 5 hours
      after volunteering as a subject for a stage hypnosis show. The suggestion given
      to terminate the trance had been that when the hypnotist said, "Goodnight",
      several subjects would feel 10,000 volts of electricity through the seat of their
      chairs. Unknown to the hypnotist, she had been phobic about electricity ever
      since a childhood shock, and would not even change a light bulb or plug in a
      cord. The coroner's verdict was death by natural causes.

PMID- 18714894
TI  - Renegotiating the social contract? The emergence of knowledge translation
      science.

PMID- 18714895
TI  - A descriptive feast but an evaluative famine: implementation research in nursing.

PMID- 18714896
TI  - Knowledge translation in the context of Aboriginal health.
AB  - Interest in the concept of knowledge translation (KT), one of the many terms used
      to describe the process(es) through which knowledge is transformed into action,
      is increasingly prevalent in the mainstream health literature. Despite a pressing
      need, little has been done to address the implications of evolving theories and
      strategies for KT in an Aboriginal context. The authors attempt to narrow the gap
      by reviewing the literature on Aboriginal KT and exploring ways to extend this
      work by engaging with the Aboriginal health research literature and the KT
      literature. They argue that the inclusion of multiple perspectives and an
      examination of the social and political context in which Aboriginal KT takes
      shape are important for the conceptual development of Aboriginal KT. This article
      is particularly relevant for those involved at the interface between nursing
      practice and efforts to improve Aboriginal health.

PMID- 18714897
TI  - Examining Appreciative Inquiry as a knowledge translation intervention in pain
      management.
AB  - Despite a solid evidence base for pain management, pain is not always well
      managed in practice. Interventions to implement pain management evidence need to
      be shifted from a focus on individual characteristics to knowledge translation
      strategies that are grounded in theory and attend to the organizational context
      and social dimension of translating evidence into practice. The authors examine
      Appreciative Inquiry (AI) as an innovative knowledge translation intervention in
      the area of pain management in nursing. Their aims are to advance the current
      state of knowledge translation interventions in pain management and to examine
      the usefulness of potential interventions based on their congruence with theory.
      The theory and practice of AI are compared to the concept of knowledge
      translation and the elements of the Promoting Action on Research Implementation
      in Health Services framework. Discussion is grounded in pain management in
      nursing.

PMID- 18714898
TI  - Accelerating client-driven care: pilot study for a social interaction approach to
      knowledge translation.
AB  - This study piloted a knowledge translation (KT) intervention promoting evidence
      based home care through social interaction. A total of 33 providers organized
      into 5 heterogeneous, geographically defined action groups participated in 5
      researcher-facilitated meetings based on the participatory action model. The KT
      evidence reflects an empowering partnership approach to service delivery.
      Exploratory investigation included quantitative pre-post measurement of outcomes
      and qualitative description of data, presented herein. The critical reflections
      of the groups reveal macro-, meso-, and micro-level barriers to and facilitators
      of KT as well as recommendations for achieving KT. Insights gleaned from the
      findings have informed the evolution of the KT intervention to engage all 3
      levels in addressing barriers and facilitators, with a conscious effort to
      transcend "push" and "pull" tendencies and enact transformative leadership. The
      findings suggest the merit of a more prolonged longitudinal investigation with
      expanded participation.

PMID- 18714899
TI  - Using consciousness-raising principles to inform modern knowledge translation
      practices in women's health.
AB  - In traditional models of knowledge translation in health care, the "expert"
      researcher disseminates empirical knowledge in a top-down manner to
      practitioners. Newer approaches extend our view of who needs to be involved in
      knowledge translation, what counts as evidence, and how knowledge exchange can be
      facilitated. Multisectoral participation and processes for collective synthesis
      of evidence increase the potential for the application of knowledge in practice
      and policy in ways that are mutually reinforcing and address structural
      inequities. The author examines the use of feminist consciousness-raising
      practices in virtual communities of practice as a viable framework for knowledge
      translation on complex health issues. Using the preliminary findings ofa study,
      she discusses how collective analysis in collaborative processes--which is at the
      heart of feminist action research--leads to engaged action by participants.

PMID- 18714900
TI  - Implementation of a two-part unit-based multiple intervention: moving evidence
      based practice into action.
AB  - This study examined the impact of a 2-part unit-based multiple intervention on
      the use by pediatric critical care nurses of best practice guidelines for
      pressure-ulcer prevention. A total of 23 nurses participated in a repeated
      measures design pre- and post-intervention to address 2 questions: Is there a
      difference in nurses' evidence-based practices following implementation of an
      educational intervention only versus implementation of both an educational and an
      innovative intervention? Are the changes sustained 6 months after completion of
      the intervention? A significant change occurred in the implementation of 2 of 11
      recommended practices following both interventions: assessment of risk of
      pressure ulcers using an age-appropriate tool (p < or = 0.001), and the
      documentation of same (p < or = 0.001). These changes may have been sustained.
      The findings bring to light the real challenges encountered when attempting to
      implement and evaluate multiple knowledge translation strategies associated with
      complex best practice guidelines in clinical practice.

PMID- 18714901
TI  - A model for evaluating knowledge exchange in a network context.
AB  - There is growing interest in the use of networks to facilitate the exchange and
      transfer of knowledge in health-care settings. The province of Ontario's Seniors
      Health Research Transfer Network (SHRTN) brings together caregivers,
      policymakers, and researchers working in the area of seniors' health to share
      knowledge derived from research and best practices. As part of an evaluation of
      SHRTN, the authors developed a model for assessing the effectiveness of knowledge
      exchange activities in a network context. The model considers the key elements of
      successful application of research evidence proposed in the Promoting Action on
      Research in Health Services (PARiHS) framework, as well as the results of these
      efforts, at 3 levels of network functioning. This model was used in a test of
      SHRTN's effectiveness as a knowledge exchange system. The results suggest that
      the framework has potential as a guide for evaluating other knowledge networks.

PMID- 18714902
TI  - The Healthy Balance Research Program: theatre as a means of knowledge
      translation.
AB  - The author examines the potential of theatre as a means of knowledge translation
      (KT). In the Healthy Balance Research Program, a community-university research
      alliance, the play Balancing Act served as a means of KT. Though the play was
      successful in meeting some of the program's KT objectives, aspects of the
      performance can be reimagined in order to maximize the KT potential of theatre.

PMID- 18714903
TI  - The Swampy Cree Tribal Council and Aboriginal governance: a case study of nursing
      education in Northern Manitoba.
AB  - This case study provides a historical account of the development of the Northern
      Bachelor of Nursing Program in the Canadian province of Manitoba through the lens
      of self-determination (governance) efforts in the fields of health and education
      by the Swampy Cree Tribal Council. Using records from the Faculty of Nursing
      archives at the University of Manitoba, the authors outline the chronology of the
      Northern Bachelor of Nursing Program in 4 phases: initiation (1982-86),
      development (1986-88), management (1986-90), and implementation and closure (1990
      94). Contemporary implications of full partnership between universities and
      Aboriginal organizations are discussed.

PMID- 18714904
TI  - The feasibility of screening for intimate partner violence during postpartum home
      visits.
AB  - There is ongoing debate and limited evidence on the effectiveness of universal
      screening for intimate partner violence (IPV). The objectives of this descriptive
      qualitative study were to examine public health nurses' (PHNs') perceptions of
      screening for IPV; explore the feasibility, from the perspective of PHNs, of IPV
      screening during home visits; describe PHNs' screening practices; and describe
      PHN training in relation to IPV. Six PHNs discussed their experiences of
      addressing IPV both in the context of a randomized trial to evaluate screening
      methods and in the context of their general home visitation practices. The
      findings indicate that universal screening for IPV using a standard set of
      questions is difficult to implement during home visits to a general population of
      new mothers. For PHNs visiting high-risk families as part of the targeted Healthy
      Babies Healthy Children program, the standard practice is to assess for mothers'
      exposure to IPV during in-depth assessment of the family; the nature of in-depth
      assessment favours a case-finding rather than a screening approach to identifying
      women exposed to IPV.

PMID- 18714905
TI  - Negotiating "home" and "care" among the HIV+ homeless: an ethnographic case study
      of home care nursing habitus.
AB  - The authors combine field work among home care nurses working in an impoverished
      urban neighbourhood with analysis of changing models of service provision. They
      explore the concepts of"home" and "care" for the homeless and marginally housed
      as features of a home care nursing "habitus" in the face of conflicting
      professional and institutional approaches to HIV care. While the nurses'
      innovative practice is a result of the failure of existing models to meet the
      needs of multi-diagnosis patients, it is also influenced by the drive to increase
      adherence to antiretroviral regimens as a means of slowing the spread of HIV at
      the population level. The authors describe the nurses' negotiated practice and
      use Pierre Bourdieu's notion of habitus to theorize about their ability to meet
      competing demands.

PMID- 18714906
TI  - Seven steps to integrating suicidology.

PMID- 18714907
TI  - Understanding self-harm and suicide websites: a qualitative interview study of
      young adult website users.
AB  - Self-harm and suicide websites have been heavily criticized both in the
      literature and the wider media, despite the fact that very little is known about
      them. To date, no study has interviewed users of these sites about them. This
      qualitative study aims to explore the accounts of young adults who engage in self
      harming and suicidal behaviors and use websites dedicated to these issues, in
      order to develop a broader understanding of these websites and to identify
      potential implications for future research. In-depth interviews were conducted
      via e-mail with 10 participants, who were recruited directly from self-harm and
      suicide websites. Using discourse analysis, we identified three main ways in
      which participants wrote about the sites. They constructed them as sources of
      empathy and understanding, as communities, and as a way of coping with social and
      psychological distress. These discourses gave users access to important, socially
      valued identities, such as being understood, belonging to a community and coping
      with their problems. If health professionals and researchers hope to understand
      people who use self-harm and suicide websites, and engage them in their services,
      they must take a more balanced view and not focus solely on the possible risks
      associated with using such sites.

PMID- 18714908
TI  - County council politicians' attitudes toward suicide and suicide prevention: a
      qualitative cross-cultural study.
AB  - The purpose of the present study was to compare county council politicians'
      attitudes toward suicide and suicide prevention in five European countries. A
      questionnaire was distributed and here the responses to the open-ended questions
      are analyzed qualitatively. Considerable differences were found in what the
      politicians in the five countries believed to be the most important causes of
      suicide and how suicide can be prevented. There were also differences in to what
      degree the politicians revealed a judgmental attitude toward suicide, which
      seemed to be related to the magnitude of the problem in the respective countries.
      A certain implicit inconsistency in the logic directing the politicians'
      responses was found when their views on causes to suicide and suicide prevention
      strategies were compared. The responses indicate a need for increased
      consciousness and knowledge about suicide and suicide prevention among
      politicians in all the five countries. This is important since they are
      responsible for initiating and funding suicide preventive efforts.

PMID- 18714909
TI  - Years of life lost from suicide in China, 1990-2000.
AB  - Suicide is an important public health problem in China: It is the fifth leading
      cause of death in China, and suicide in China accounts for over 30% of the
      world's overall suicide deaths. The substantial burden due to suicide has not
      been well recognized. This study aims to provide an estimate of the socioeconomic
      burden of the suicide problem in China in terms of years of life lost (YLL) and
      to discuss its implications. Suicide rates and the related YLL by age, gender,
      and region (urban/rural) from 1990 to 2000 were estimated using the most recent
      data from the Ministry of Health of China. The suicide rate in rural China was
      three times higher than that in urban areas. Suicide completers in rural areas
      shared 90% of total YLL. Rural women aged 25-39 years contributed the largest
      share of YLL. Our results show that some population subgroups contributed a
      disproportionate share to the disease burden of suicide. National strategies for
      suicide prevention should include targeted programs in catering the need of these
      specified subgroups in China.

PMID- 18714910
TI  - Suicidal behavior as communication in a cultural context: a comparative study
      between Uganda and Norway.
AB  - In this study, we attempt to even out some of the imbalance in suicide research
      caused by the fact that most such research has been conducted in the Western part
      of the world with the corresponding common disregard of the potential problems in
      generalizing findings to different cultural settings. Our point of departure was
      to look at suicidal behavior as communication and our main purpose was to
      investigate whether Qvortrup's semiotic four-factor model, which has been
      empirically supported in the West, would be applicable in an African context,
      exemplified by Uganda. Interviews of patients admitted to hospital following an
      act of nonfatal suicidal behavior were conducted in Uganda and Norway and the
      data were compared. The results showed that the four-factor structure found in
      the West was not applicable in the Ugandan context, but that two by two of these
      factors were collapsed into a two-factor model in Uganda: One factor regarding
      the external dialog and one factor regarding the internal dialog. Some
      differences and some similarities were found between Norway and Uganda when
      suicidal behavior was considered as a communicative act. The results are
      discussed in terms of the differences in the psychological characteristics of the
      suicidal persons in the two countries, as well as the different cultural settings
      of the study.

PMID- 18714911
TI  - Suicide and undetermined deaths among youths and young adults in Latin America:
      comparison with the 10 major developed countries--a source of hidden suicides?
AB  - In Latin American (LA) and the major developed countries' (MDC) suicide and
      undetermined deaths are analyzed as methods of suicide and the number of
      undetermined deaths are similar, possibly containing hidden suicides. The goal
      was to test the likelihood that LA cultural attitudes lead to higher undetermined
      rates and more hidden suicides. We used 3-year WHO average mortality data to
      compare LA and MDC mortality by age and gender, and chi2 tests to examine any
      differences. In 13 LA countries younger-aged (15-34) men and women's suicides
      were higher than all-age rates, and undetermined deaths exceeded the suicide
      rates. Nine LA countries had significantly more undetermined younger-aged male
      deaths than females. Sixteen of 18 LA countries had significantly higher
      undetermined death rates than the MDC. LA younger-aged malefs24 146s differential
      suicide: Undetermined rates indicated they may contain substantial numbers of
      hidden suicides. Inadvertently, cultural attitudes to suicide may hinder
      prevention.

PMID- 18714912
TI  - History of childhood abuse and neglect and suicidal behavior at hospital
      admission.
AB  - Suicide is a major public health problem. Preventive measures have been sought by
      identifying risk factors. This study evaluates the association of childhood abuse
      and neglect with suicidal behavior at the time of psychiatric hospital admission.
      A total of 120 subjects (72 females; mean age 42.5 +/- 15.6 years old) admitted
      from August 2006 to July 2007 completed the Childhood Trauma Questionnaire (CTQ)
      to assess severity of exposure to childhood maltreatment. Thereof 62 (51.6%)
      patients presented with suicidal behavior at admission. Patients who had
      attempted suicide had significantly higher CTQ scores. Regression analysis
      indicated that shorter illness duration and severity of childhood maltreatment
      were predictors of suicidal behavior at admission. The study showed that
      inpatients of a psychiatric unit of a general hospital who experienced severe
      childhood abuse or neglect were significantly more likely to present with
      suicidal behavior. History of childhood maltreatment should be evaluated as an
      associated risk factor of suicidal behavior at admission of psychiatric
      inpatients.

PMID- 18714913
TI  - Pattern of deliberate self-harm in young people in Karachi, Pakistan.
AB  - Globally, suicide remains one of the leading causes of death among individuals
      aged 10 to 64 years and it ranks between second and fourth among those age 10 to
      45 years. Data on suicidal behavior from Pakistan is sparse, especially for
      children and adolescents. A retrospective descriptive case note study was carried
      out of all patients under the age of 18 years (n = 69) admitted with deliberate
      self-harm (DSH) to a university hospital in Karachi, Pakistan. Females (63.8%)
      outnumbered males by 1.7:1. The mean age of the group was 16 years (+/- 2.2). The
      most frequent method used was benzodiazepine overdose (30.4%). "Family conflicts"
      was the main stressor reported by 66.7%. The most frequent diagnosis made was
      major depressive disorder in 18%. Despite the fact that 98% of our sample was
      Muslims and suicide is strictly forbidden in Islam, 76.8% expressed their intent
      to die. Multivariate logistic regression found current stressor to be
      significantly associated with an intention to die. Patients with nonfatal
      suicidal behavior form a pool for future suicides. Preventive efforts should be
      directed at this group. School based programs would be an effective way of
      addressing this.

PMID- 18714914
TI  - The most common method of suicide in Tehran 2000-2004: implications for
      prevention.
AB  - The likelihood of completing suicide depends to some extent on knowledge of
      effective means and also on the availability and/or acceptability of such
      methods. Since studying suicide methods may have an implication for prevention,
      the focus of this study was on the most favored method of suicide in Tehran,
      Iran. The study uses confirmed suicide data provided by the Beheshet Zahra
      Organization (BZO), which gathers all mortality data within Tehran and enters
      them into a computerized database, from which the relevant information for all
      the recorded suicide cases during the year 2000 to 2004 were obtained and
      analyzed. There were 703 cases of suicide (632 males and 71 females) in the BZO
      database, with a sex ratio of 8.9. The mean (standard deviation) of age at
      suicide for those who chose hanging and for those who have chosen other methods
      of suicide were 33.93 (14.2) and 34.60 (13.4) years, respectively. Hanging was
      the method favored by 572 (85.9%) of cases. Use of hanging was higher in females
      (61, 85.9%) than in males (511, 80.9%), and higher among the married (304, 53.6%)
      than among singles (268, 46.4%). The high proportion of persons using hanging as
      a method of suicide in Tehran may reflect the fact that this method is more
      acceptable and/or easily available and/or less likely to be misclassified as
      accidental or undetermined death. The prevention of such suicides is extremely
      difficult in the general population. Therefore, it is suggested that, to prevent
      suicide by hangings, the authorities should focus on the causal factors of
      suicide rather than on the acceptability and/or the availability of this method.

PMID- 18714915
TI  - A reassuring glimpse into the future.

PMID- 18714916
TI  - Cross sectional survey of ultrasound use for central venous catheter insertion
      among resident physicians.
AB  - BACKGROUND: Use of ultrasound guidance for Central Venous Catheter insertion has
      been associated with decreased complications and increased success rates.
      Previous reports show low rates of use among physicians. OBJECTIVES: Evaluation
      of the frequency of Ultrasound Guidance use for Central Venous Catheter insertion
      among residents at a teaching institution. METHODS: A cross sectional electronic
      survey of resident physicians at a tertiary care teaching hospital was conducted
      to evaluate use of Ultrasound Guidance for Central Venous Catheterization.
      Assessment included self reported frequency of ultrasound guidance use, and
      volume of central venous catheter placement. Attitudes toward the use of
      ultrasound were assessed using Likert scales. RESULTS: There is a high rate. over
      90%, of ultrasound guidance use for Internal Jugular central venous catheters
      among residents. The majority of residents use sterile real-time imaging with a
      single operator with a reported success rate greater then 80%. CONCLUSIONS:
      Resident use of ultrasound guidance for Internal Jugular central venous catheter
      insertion can be much higher than previously reported in the literature.

PMID- 18714917
TI  - The founders of the Medical Society of Delaware: Doctor James Sykes.

PMID- 18714918
TI  - A legacy to inspire.

PMID- 18714919
TI  - The arts and the mind-full doctor.

PMID- 18714920
TI  - Grocery store care.

PMID- 18714921
TI  - Finding harmony. Medicine anchors the life and music feeds the soul of family
      physician Stanley Woolner.

PMID- 18714922
TI  - Beautiful people. Through photography, Rick Guidotti captures the individuality
      and beauty of his subjects, all of whom have genetic disorders and conditions.

PMID- 18714923
TI  - Soothing tunes.

PMID- 18714924
TI  - A season for action.

PMID- 18714925
TI  - Improving Palliative care. Interview by Scott D Smith.

PMID- 18714926
TI  - A medical education.

PMID- 18714927
TI  - Fear.

PMID- 18714928
TI  - Poetic podcasts: the importance of the humanities in medicine.

PMID- 18714929
TI  - Amy. A child's brief life brings a physician into the fold of her family and
      traditional Hmong medicine.

PMID- 18714930
TI  - Dispelling the chronic Lyme disease myth.
AB  - Lyme disease is a tick-borne illness endemic to Minnesota that can have
      potentially severe complications. As the incidence of Lyme disease continues to
      increase, it is important for physicians in Minnesota to become familiar with its
      clinical aspects, including the concept of "chronic Lyme disease." Chronic Lyme
      disease is a misnomer that is often applied to patients with nonspecific
      presentations who may or may not have a history of infection with Borrelia
      burgdorferi, the agent that causes Lyme disease. When a patient does present with
      persistent nonspecific symptoms attributed to chronic Lyme disease, clinicians
      should ascertain the presence of objective manifestations, obtain laboratory
      results, and get a history of tick exposure. If active infection with B.
      burgdorferi is unlikely, they should avoid prescribing empiric antibiotic therapy
      and instead thoroughly evaluate the patient for other possible causes of the
      complaints and recommend appropriate care.

PMID- 18714931
TI  - Neglected tropical disease: challenges, progress, and hope.

PMID- 18714932
TI  - Perspectives on periodontal risk factors.
AB  - The development of a clinical decision tree based on knowledge about risks and
      reported outcomes of therapy is a necessity for successful planning and outcome
      of periodontal therapy. This requires a well-founded knowledge of the disease
      entity and a broad knowledge of how different risk conditions attribute to
      periodontitis. The infectious etiology, a complex immune response, and influence
      from a large number of co-factors are challenging conditions in clinical
      periodontal risk assessment. The difficult relationship between independent and
      dependent risk conditions paired with limited information on periodontitis
      prevalence adds to difficulties in periodontal risk assessment. The current
      information on periodontitis risk attributed to smoking habits, socio-economic
      conditions, general health and subjects' self-perception of health, is not
      comprehensive, and this contributes to limited success in periodontal risk
      assessment. New models for risk analysis have been advocated. Their utility for
      the estimation of periodontal risk assessment and prognosis should be tested. The
      present review addresses several of these issues associated with periodontal risk
      assessment.

PMID- 18714933
TI  - Early diagnosis and treatment options for the periodontal problems in Papillon
      Lefevre syndrome: a literature review.
AB  - Various approaches for treating the periodontal condition associated with
      Papillon-Lefevre syndrome (PLS) have been reported. These include oral hygiene
      instruction, use of mouth rinses, frequent debridement, multiple antibiotic
      regimens, periodontal surgery, extraction of hopeless teeth, and extraction of
      all primary teeth. The objective of this paper is to review the literature on the
      different treatment approaches of patients with PLS and to illustrate the
      importance of early diagnosis as well as treatment in long-term maintenance of
      oral health. Because PLS is rare, most publications are case reports, and very
      few document long-term successful treatment of the periodontal condition. Several
      treatment approaches are summarized in this paper with the long-term reports. The
      importance of early diagnosis is highlighted. The recommendation is that young
      patients with skin lesions and severe periodontal destruction together with
      premature loss of teeth should be referred to a periodontist as early as
      possible. This should prevent or delay tooth loss and enhance early replacement
      of missing teeth for preservation of function and esthetics. In conclusion,
      successful periodontal management of PLS patients remains challenging. However,
      as our understanding of the etiological factors increases, it is hoped that
      successful treatment strategies will be developed.

PMID- 18714934
TI  - Comparative clinical study of a subepithelial connective tissue graft and
      acellular dermal matrix graft for the treatment of gingival recessions: six- to
      12-month changes.
AB  - Different techniques have been proposed for the treatment of gingival recession.
      This study compared the clinical results of gingival recession treatment using a
      subepithelial connective tissue graft and an acellular dermal matrix allograft.
      Seven patients with bilateral Miller class I or II gingival recession were
      selected. Twenty-six recessions were treated and randomly assigned to the test
      group. In each case the contralateral recession was assigned to the control
      group. In the control group, a connective tissue graft in combination with a
      coronally positioned flap was used; in the test group, an acellular dermal matrix
      allograft was used as a substitute for palatal donor tissue. Probing depth,
      clinical attachment level, gingival recession, and width of keratinized tissue
      were measured two weeks prior to surgery and at six and 12 months post-surgery.
      There were no statistically significant differences between the groups in terms
      of recession reduction, clinical attachment gain, probing pocket depth, and
      increase in the width of the keratinized tissue after six or 12 months. There was
      no statistically significant increase in the width of keratinized tissue between
      six and 12 months for either group. Within the limitations of this study, it can
      be suggested that the acellular dermal matrix allograft may be a substitute for
      palatal donor tissue in root coverage procedures and that the time required for
      additional gain in the amount of keratinized tissue may be greater for the
      acellular dermal matrix than for the connective tissue procedures.

PMID- 18714935
TI  - Polymorphism of genes encoding toll-like receptors and inflammatory cytokines in
      periodontal disease in the Japanese population.
AB  - Periodontitis, which is a widespread and major dental disease, is a
      multifactorial, lifestyle-related disease and has been analyzed for gene
      polymorphism. We examined the frequency of the polymorphisms of the pro
      inflammatory cytokine genes IL-1 A (-889) and IL-1 B (+3953) in relation to
      periodontitis in the Japanese population. We also examined whether polymorphism
      of TLR2 (Arg677Trp) and TLR4 (Asp299Gly), which are receptors recognized by
      periodontopathic bacteria, may also be associated with periodontitis. The
      subjects were 92 Japanese individuals, among whom 43 had periodontitis and 49
      were healthy controls. We isolated genomic DNA from lingual mucosal cells and
      tested them for single nucleotide polymorphisms by polymerase chain reaction
      restriction fragment length polymorphism. The incidence of polymorphisms was
      analyzed statistically by Fisher's exact test, and the sensitivity and
      specificity of the gene polymorphisms were calculated. The purpose was to
      determine whether such polymorphisms might be effectively used in the diagnosis
      of periodontitis. However, we found no evidence that the gene polymorphism of IL
      1A (p = 0.082), IL-1 B (p = 0.180), TLR2 (p = 1.000) or TLR4 (p = 1.000) and
      overall gene polymorphism in any of the genes (p = 0.752) correlate with
      periodontitis. The sensitivity (14.0%) and specificity (83.7%) of the mutations
      found in all of the genes were low. Therefore, we advise against using the
      analyses of polymorphism of these genes to detect periodontitis in the Japanese
      population.

PMID- 18714936
TI  - [Efficacy of oral calcium and/or sodium phosphate in the prevention of parturient
      paresis in cows].
AB  - The goal of this study was to investigate the efficacy of calcium chloride,
      sodium phosphate or a combination of these two substances administered orally
      immediately postpartum for the prevention of parturient paresis in cows. Thirty
      two cows that had had parturient paresis at the previous calving, and in which
      serum biochemistry had shown hypocalcaemia and hypophosphataemia, were used in
      the study. The cows were transferred to the Department of Farm Animals,
      University of Zurich, five days before their expected due dates. On a randomized
      trial, the cows were given calcium chloride, sodium phosphate, both substances or
      no treatment (controls) via a stomach tube immediately postpartum and 12 hours
      later. The cows were monitored for 96 hours during which time blood was collected
      on a regular basis for the determination of total calcium, ionized calcium,
      inorganic phosphorus and magnesium concentrations. Of the 32 cows treated, 19
      (59%) had parturient paresis and 13 (41%) did not. The incidence of parturient
      paresis did not differ significantly among the groups although there was a
      tendency for a lower incidence in cows treated with both calcium chloride and
      sodium phosphate. The various treatments had no apparent effect on serum calcium
      concentration. The concentration of inorganic phosphorus increased significantly
      in cows treated with sodium phosphate compared with the controls. The results of
      this study showed that cows treated with both calcium chloride and sodium
      phosphate orally tended to have a lower incidence of parturient paresis. Further
      investigation into multiple administrations of oral calcium chloride and sodium
      phosphate, started before parturition, for the prevention of parturient paresis
      is required.

PMID- 18714937
TI  - Emergence of methicillin-resistant Staphylococcus pseudintermedius in
      Switzerland: three cases of urinary tract infections in cats.
AB  - Methicillin resistance has emerged in clinical isolates of Staphylococcus
      pseudintermedius from cats in Switzerland. Three cats suffering from urinary
      tract infections were infected with methicillin-resistant S. pseudintermedius
      (MRSP). Phenotypic and genotypic characterization of the resistance profile
      showed that the isolates displayed resistance to all beta-lactams and
      cephalosporins (blaZ, mecA), fluoroquinolones, tetracyclines [tet(K)],
      macrolides, lincosamides and streprogramins B [erm(B)], chloramphenicol
      (catpC221), trimethoprim [dfr(G)] and the aminoglycosides gentamicin [aac(6')-Ie
      aph(2')-Ia], kanamycin and neomycin [aph(3')-III] and streptomycin [ant(6)-Ia].
      They also harbor the leukocidin gene lukS-I. MRSP represents a new challenge for
      antibiotic therapy and this zoonotic bacteria may rapidly spread to animals and
      humans.

PMID- 18714938
TI  - [Housing situation of small animals in Swiss pet shops].
AB  - This study investigates the situation regarding housing of small animals in Swiss
      pet shops. Data of 92 pet shops were collected with a questionnaire. On average
      813 fish, 52.5 invertebrates, 32.2 small mammals, 26.9 birds, 8.9 reptiles and
      2.7 amphibians were offered for sale per pet shop. Small mammals, birds and
      reptiles were mainly obtained from Swiss breeders, while fish and amphibians were
      almost exclusively purchased from foreign providers. The housing systems which
      were sold differed from those in which the animals were kept in the shop. This
      may be misleading to the future pet owners and may lead to faulty husbandry.
      Animals on reserve were often kept in different housing systems than those in the
      pet shop. Sick animals were usually treated or killed by the pet shop owners. The
      killing methods varied between the various species.

PMID- 18714939
TI  - [Drug interactions of phenylbutazone and phenprocoumon in a warmblood gelding].
AB  - A 15 year old Oldenburger gelding was treated during 3 weeks for laminitis with
      the anticoagulant phenprocoumone (27 mg orally, once daily) and concurrent
      administration of phenylbutazone (2-4 g orally, twice daily). After this
      treatment the animal was presented to the Equine Clinic University of Zurich with
      a history of acute colic and advanced symptoms of shock. On the basis of the
      clinical signs and laboratory values, a diagnosis of combined drug induced
      coagulopathy was made. The horse was treated with the antidote Vitamine-K1 (0.5
      mg/kg, subcutaneously). Eventually, the general condition of the animal worsened
      and it was therefore euthanized. Necropsy revealed profound, multifocal
      hemorrhagic diathesis of the serosal surface of the viscera, as well as bleeding
      into the visceral cavities. This case shows that concurrent administration of
      phenprocoumone and phenylbutazone may lead to drug interactions that increase the
      anticoagulation effect of the coumarine-derivative. Simultaneous use of coumarine
      derivatives and phenylbutazone is therefore contraindicated due to the higher
      risk of bleeding. A reasonable treatment of horses with anticoagulants requires
      regular monitoring with constant evaluation of coagulation status and special
      attention to potential drug interactions.

PMID- 18714940
TI  - [Intraocular hemorrhage in a goat with thrombocytopenia and metastasis of an
      adenocarcinoma in the iris].
AB  - This case report describes the findings in a 10-year-old goat with metastasis of
      an adenocarcinoma in the iris. Two weeks before admission, the owner had noticed
      blepharospasm of the left eye. Clinical examination by the referring veterinarian
      revealed unilateral intraocular hemorrhage. The goat was referred to our clinic
      for further work-up. The rectal temperature was 40 degrees C. The most important
      haematological result was severe thrombocytopenia. There was mild corneal oedema
      of the left eye. Approximately 75 per cent of the anterior chamber was filled
      with non-coagulated blood. The fluid in the anterior chamber dorsal to the blood
      was cloudy, and the corpora nigra could not be seen clearly. All other internal
      parts of the eye could not be seen. Ultrasonography of the left eye confirmed
      cloudiness of the anterior chamber and revealed moderate thickening of the iris.
      The right prescapular lymph node was markedly enlarged. Cytological examination
      of a fine needle aspirate of the lymph node showed a mixed population of
      neoplastic cells. Based on immunohistochemical evaluation of the cells metastasis
      of a carcinoma was diagnosed. The goat was subjected to euthanasia, and a
      postmortem examination was carried out. The anterior chamber of the left eye
      contained blood, and the iris was thicker than normal and adhered to the
      posterior surface of the cornea. There were neoplastic alterations in the iris,
      the oesophagus, the lung lobes, the liver, the kidney and in the prescapular,
      retropharyngeal, mediastinal and hepatic lymph nodes. Histologically, a diagnosis
      of carcinoma was confirmed, but the origin of the tumour could not be determined.

PMID- 18714941
TI  - [Stipulation of sick day insurance].

PMID- 18714942
TI  - [To collect: reminder, prosecution, court proceedings].

PMID- 18714943
TI  - [FIV: no death sentence ABCD: "Don't put a cat down just because she is FIV
      positive!" ].

PMID- 18714944
TI  - [The Vetsuisse course and the reorganization of the veterinary education system
      after "Bologne"].

PMID- 18714945
TI  - Kinetics and product branching ratios of the reaction of (1)CH2 with H2 and D2.
AB  - The reactions of singlet methylene (a(1)A1 (1)CH2) with hydrogen and deuterium
      have been studied by experimental and theoretical techniques. The rate
      coefficients for the removal of singlet methylene with H2 (k1) and D2 (k2) have
      been measured from 195 to 798 K and are essentially temperature-independent with
      values of k1 = (10.48 +/- 0.32) x 10(-11) cm(3) molecule(-1) s(-1) and k2 = (5.98
      +/- 0.34) x 10(-11) cm(3) molecule(-1) s(-1), where the errors represent 2sigma,
      giving a ratio of k1/k2 = 1.75 +/- 0.11. In the reaction with H2, singlet
      methylene can be removed by reaction giving CH3 + H or deactivated to ground
      state triplet methylene. Direct measurement of the H atom product showed that the
      fraction of relaxation decreased from 0.3 at 195 K to essentially zero at 398 K.
      For the reaction with deuterium, either H or D may be eliminated. Experimentally,
      the H:D ratio was determined to be 1.8 +/- 0.5 over the range 195-398 K.
      Theoretically, the reaction kinetics has been predicted with variable reaction
      coordinate transition state theory and with rigid-body trajectory simulations
      employing various high-level, ab initio-determined potential energy surfaces. The
      magnitudes of the calculated rate coefficients are in agreement with experiment,
      but the calculations show a significant negative temperature dependence that is
      not observed in the experimental results. The calculated and experimental H to D
      ratios from the reaction of singlet methylene with D2 are in good agreement,
      suggesting that the reaction proceeds entirely through the formation of a long
      lived methane intermediate with a statistical distribution of energy.

PMID- 18714946
TI  - Evaluation of incremental correlation energies for open-shell systems:
      application to the intermediates of the 4-exo cyclization, arduengo carbenes and
      an anionic water cluster.
AB  - A fully automated procedure for incremental closed-shell CCSD calculations has
      been extended to open-shell cases tractable with the restricted open-shell CCSD
      method. It is demonstrated that for monoradical intermediates of the 4-exo
      cyclization, the triplet state of Arduengo carbenes as well as for water cluster
      anions chemical accuracy can be reached with respect to the error introduced by
      the local correlation treatment. Finally, it is shown that the computationally
      less demanding evaluation of higher-order increments in a smaller basis set does
      not lead to significant errors.

PMID- 18714947
TI  - Highly accurate first-principles benchmark data sets for the parametrization and
      validation of density functional and other approximate methods. Derivation of a
      robust, generally applicable, double-hybrid functional for thermochemistry and
      thermochemical kinetics.
AB  - We present a number of near-exact, nonrelativistic, Born-Oppenheimer reference
      data sets for the parametrization of more approximate methods (such as DFT
      functionals). The data were obtained by means of the W4 ab initio computational
      thermochemistry protocol, which has a 95% confidence interval well below 1
      kJ/mol. Our data sets include W4-08, which are total atomization energies of over
      100 small molecules that cover varying degrees of nondynamical correlations, and
      DBH24-W4, which are W4 theory values for Truhlar's set of 24 representative
      barrier heights. The usual procedure of comparing calculated DFT values with
      experimental atomization energies is hampered by comparatively large experimental
      uncertainties in many experimental values and compounds errors due to
      deficiencies in the DFT functional with those resulting from neglect of
      relativity and finite nuclear mass. Comparison with accurate, explicitly
      nonrelativistic, ab initio data avoids these issues. We then proceed to explore
      the performance of B2x-PLYP-type double hybrid functionals for atomization
      energies and barrier heights. We find that the optimum hybrids for hydrogen
      transfer reactions, heavy-atoms transfers, nucleophilic substitutions, and
      unimolecular and recombination reactions are quite different from one another:
      out of these subsets, the heavy-atom transfer reactions are by far the most
      sensitive to the percentages of Hartree-Fock-type exchange y and MP2-type
      correlation x in an (x, y) double hybrid. The (42,72) hybrid B2K-PLYP, as
      reported in a preliminary communication, represents the best compromise between
      thermochemistry and hydrogen-transfer barriers, while also yielding excellent
      performance for nucleophilic substitutions. By optimizing for best overall
      performance on both thermochemistry and the DBH24-W4 data set, however, we find a
      new (36,65) hybrid which we term B2GP-PLYP. At a slight expense in performance
      for hydrogen-transfer barrier heights and nucleophilic substitutions, we obtain
      substantially better performance for the other reaction types. Although both B2K
      PLYP and B2GP-PLYP are capable of 2 kcal/mol quality thermochemistry, B2GP-PLYP
      appears to be the more robust toward nondynamical correlation and strongly polar
      character. We additionally find that double-hybrid functionals display excellent
      performance for such problems as hydrogen bonding, prototype late transition
      metal reactions, pericyclic reactions, prototype cumulene-polyacetylene system,
      and weak interactions.

PMID- 18714948
TI  - Substituent effects on singlet-triplet gaps and mechanisms of 1,2-rearrangements
      of 1,3-oxazol-2-ylidenes to 1,3-oxazoles.
AB  - Electronic structures, partial atomic charges, singlet-triplet gaps (Delta E ST),
      substituent effects, and mechanisms of 1,2-rearrangements of 1,3-oxazol-2-ylidene
      ( 5) and 4,5-dimethyl- ( 6), 4,5-difluoro- ( 7), 4,5-dichloro- ( 8), 4,5-dibromo-
      ( 9), and 3-methyl-1,3-oxazol-2-ylidene ( 10) to the corresponding 1,3-oxazoles
      have been studied using complete-basis-set methods (CBS-QB3, CBS-Q, CBS-4M),
      second-order Moller-Plesset perturbation method (MP2), hybrid density functionals
      (B3LYP, B3PW91), coupled-cluster theory with single and double excitations (CCSD)
      and CCSD plus perturbative triple excitations [CCSD(T)], and the quadratic
      configuration interaction method including single and double excitations (QCISD)
      and QCISD plus perturbative triple excitations [QCISD(T)]. The 6-311G(d,p), 6
      31+G(d,p), 6-311+G(d,p), and correlation-consistent polarized valence double-xi
      (cc-pVDZ) basis sets were employed. The carbenes have singlet ground states, and
      the CBS-QB3 and CBS-Q methods predict Delta E ST values for 5- 8 and 10 of 79.9,
      79.8, 74.7, 77.0, and 82.0 kcal/mol, respectively. CCSD(T), QCISD(T), B3LYP, and
      B3PW91 predict smaller Delta E ST values than CBS-QB3 and CBS-Q, with the hybrid
      density functionals predicting the smallest values. The concerted unimolecular
      exothermic out-of-plane 1,2-rearrangements of singlet 1,3-oxazol-2-ylidenes to
      their respective 1,3-oxazoles proceed via cyclic three-center transition states.
      The CBS-predicted barriers to the 1,2-rearrangements of singlet carbenes 5- 9 to
      their respective 1,3-oxazoles are 41.4, 40.4, 37.8, 40.4, and 40.5 kcal/mol,
      respectively. During the 1,2-rearrangements of singlet 1,3-oxazol-2-ylidenes 5-
      9, there is a decrease in electron density at oxygen, N3 (the migration origin),
      and C5 and an increase in electron density at C2 (the migration terminus), C4,
      and the partially positive migrating hydrogen.

PMID- 18714949
TI  - Stereoelectronic interaction and their effects on conformational preference for 2
      substituted methylenecyclohexane: an experimental and theoretical investigation.
AB  - Conformational preferences for 2-substituted methylenecyclohexanes were
      determined using (3) J H 2 H 3 spin-spin coupling constants, while
      stereoelectronic interactions were obtained by means of theoretical calculations
      and NBO analysis. The conformational equilibrium of compounds studied can be
      represented by their axial and equatorial conformers, the axial conformers being
      the most stable form in polar and nonpolar solvents. These conformational
      preferences were attributed to the hyperconjugative interactions between the pi C
      C-->sigma* C-Xax. and sigma C-H-->sigma* C-Xax. orbitals, and the repulsive
      steric interaction observed between sigma C-H-->n Xeq..

PMID- 18714950
TI  - Peculiarity in the electronic structure of Cu(II) complex ferromagnetically
      coupled with bisimino nitroxides.
AB  - By means of the electron spin resonance (ESR) technique, we have investigated the
      electronic structures of the tridentate imino nitroxyl diradical complex with
      copper(II) (Cu-bisimpy), which has a square planar structure and a ground quartet
      state with an extremely strong ferromagnetic exchange interaction, and its
      related compounds (bisimpy = 2,6-bis(1'-oxyl-4',4',5',5'-tetramethyl-4',5'
      dihydro-1' H-imidazol-2'-yl)pyridine). It was clarified that Cu-bisimpy had
      unique magnetic orbitals, compared with the biradical ligand (bisimpy), a
      zinc(II) biradical complex (Zn-bisimpy) and a copper(II) terpyridine complex (Cu
      tpy) (tpy = 2,2';6',2''-terpyridine). Multifrequency ESR spectroscopy provided a
      reliable set of magnetic parameters of Cu-bisimpy, which has a small g anisotropy
      ( g x = 2.02, g y = 2.01, g z = 2.08) and small hyperfine coupling with Cu (|A x|
      = 42.0 MHz, |A y|<or= 14 MHz, |A z| = 153 MHz) but huge zero-field splitting (D =
      +17.4 GHz, E = -1.0 GHz). The maximum principal axis of zero-field interaction (
      z ZF) is perpendicular to the z axis for the g and A tensors, which is normal to
      the molecular plane. These characteristics of the magnetic properties prove that
      the substantial spin transfer from the d x (2) - y (2) orbital of copper to the n
      orbitals of the ligand is caused by a sigma-type covalent bonding effect between
      the central metal and the ligand nitrogens. The covalent bonding effect produces
      carbene configurations on the nitrogen atoms of the imino nitroxyl radicals. The
      carbene configuration was concluded to be the main reason for the strong
      ferromagnetic coupling in Cu-bisimpy. Multifrequency electron spin resonance
      spectroscopy clarified the unique electronic structure of a square planar
      copper(II) complex with an imino nitroxyl diradical, which undergoes a strong
      ferromagnetic interaction caused by a covalent bonding effect.

PMID- 18714951
TI  - Formation of an ion-pair molecule with a single NH(+)...Cl(-) hydrogen bond:
      Raman spectra of 1,1,3,3-tetramethylguanidinium chloride in the solid state, in
      solution, and in the vapor phase.
AB  - Some ionic compounds (salts) form liquids when heated to temperatures in the
      range of 200-300 degrees C. They may be referred to as moderate temperature ionic
      liquids. An example of such a compound is the 1,1,3,3-tetramethylguanidinium
      chloride, [TMGH]Cl, melting at approximately 212 degrees C. The chemistry of this
      compoundcontaining a dimeric ion-pair "molecule"was investigated in the solid
      state, in solutions in water and ethanol, and in the vapor phase, based on ab
      initio molecular orbital density functional theory (DFT)-type calculations with 6
      311+G(d,p) basis sets. Calculations on the monomeric [TMGH] (+) ion and the
      dimeric chloride ion-pair salt converged to give geometries near the established
      crystal structure of [TMGH]Cl. The structures and their binding energies are
      given as well as calculated vibrational harmonic normal modes (IR and Raman band
      wavenumbers and intensities). Experimentally obtained Raman scattering spectra
      are presented and assigned, by comparing to the quantum mechanical calculations.
      It is concluded that dimeric molecular ion pairs with four N-H (+)...Cl (-)
      hydrogen bonds probably exist in the solutions and are responsible for the
      relatively high solubility of the "salt" in ethanol. It was discovered that the
      compound can be easily sublimed by heating to about 200-230 degrees C. In the
      Raman spectrum of the vapor at 225 degrees C, a characteristic strong band at
      2229 cm (-1) was found and interpreted to show that the gas phase consists of
      monomeric ion-pair "molecules" held together by a single N-H (+)...Cl (-)
      hydrogen bond, the stretching band of which is causing the band.

PMID- 18714952
TI  - Reactant stationary approximation in enzyme kinetics.
AB  - In the application of the quasi-steady-state approximation, it is generally
      assumed that there is an initial transient during which the substrate
      concentration remains approximately constant while the complex concentration
      builds up. In this paper, we address the assumption that the substrate
      concentration does not change significantly during this initial transient and
      name it the reactant stationary approximation. For the single enzyme, single
      substrate reaction, the reactant stationary approximation is generally considered
      a sufficient condition to apply the quasi-steady-state approximation. Studying
      the dynamic behavior of this reaction with endogenous substrate, we show that the
      quasi-steady-state approximation and reactant stationary approximation are two
      separate approximations. We discuss the consequence of this result for the
      determination of reaction parameters in enzyme catalyzed reactions.

PMID- 18714953
TI  - An experimental and theoretical study of NSCl decomposition in the presence of
      trace amounts of water.
AB  - An experimental and density functional theory study of the decomposition reaction
      of NSCl with water molecule(s) into NH 3 and SO 2 is described. Experiments
      involving the decomposition of NSCl in the presence of trace amounts of water
      showed that the formation of both HNSO and SO 2 is faster when the cell and the
      cell surface are fresh and more likely to be coated in adsorbed water. The
      density functional theory computational results suggest that the decomposition
      involves two main steps: reactions 1 NSCl + nH 2O --> HNSO + ( n - 1) H 2O + HCl
      and 2 HNSO + nH 2O --> NH 3 + SO 2 + ( n - 1)H 2O. The barrier for reaction 1 in
      which NSCl decomposes to form HNSO becomes substantially lower when the explicit
      hydrogen bonding of water molecules is considered. The water assisted
      decomposition reaction mechanism can help account for the experimentally observed
      conversion of NSCl to produce HNSO in the presence of water. The calculated
      barrier of reaction 2 (the decomposition of HNSO into NH 3 and SO 2) can also
      explain the experimental observation of SO 2 bands from the decomposition of NSCl
      in the presence of water.

PMID- 18714954
TI  - Reactions over multiple, interconnected potential wells: unimolecular and
      bimolecular reactions on a C3H5 potential.
AB  - In this article we analyze quantitatively and discuss in detail a number of
      reactions that take place on a C3H5 potential. These reactions include the
      reaction of hydrogen atoms with allene and propyne, the reaction of methyl with
      acetylene, the isomerization of cyclopropyl to allyl, and the dissociation of
      allyl, 1-propenyl, and 2-propenyl. The theory employs high-level electronic
      structure methods to characterize the potential energy surface, RRKM theory to
      calculate microcanonical, J-resolved rate coefficients, and master-equation
      methods to determine phenomenological rate coefficients, k(T,p). The agreement
      between our theory and the experimental results available is very good. The final
      theoretical results are cast in a form that is convenient for use in chemical
      kinetics modeling.

PMID- 18714955
TI  - Electronic structure, molecular interaction, and stability of the CH4-nH2O
      complex, for n = 1-21.
AB  - Molecular calculations were carried out with four different methodologies to
      study the CH 4- nH 2O complex, for n = 1-21. The HF and MP2 methods used
      considered the O atom with pseudopotential to freeze the 1s shell. The other
      methodologies applied the Bhandhlyp and B3lyp exchange and correlation
      functionals. The optimized CH 4- nH 2O structures are reported, specifying the
      number and type of H 2O subunits (triangle, square, pentagon, etc.) that
      comprised the nH 2O counterpart cluster or cage, that interacted with the CH 4
      molecule, and, in the latter case, that provided its confinement. Results are
      focused to understand the stability of the CH 4- nH 2O complex. The quality of
      the electron correlation effect, as well as the size of the nH 2O cage to confine
      the guest molecule, and the number and type of H 2O subunits comprising the nH 2O
      cluster or cage are the most important factors to provide the stability of the
      complex and also dictate the particular n value at which the CH 4 molecule
      confinement occurs. This number was 14 for the HF, Bhandhlyp, and B3Lyp methods
      and 16 for the MP2 method. The reported hydrate structures for n < 20 could be
      predictive for future experiments.

PMID- 18714956
TI  - No-pair bonding in coinage metal dimers.
AB  - High-level ab initio calculations at the coupled cluster with single and double
      substitutions and perturbative treatment of triple substitutions, CCSD(T), level
      of theory have been carried out for the dimers of coinage metal atoms Cu, Ag, and
      Au in the ground 1Sigma(g)+ state and in the excited 3Sigma(u)+ state. All of the
      calculations have been carried out with the inclusion of scalar-relativistic
      effects via the normalized elimination of the small component (NESC) method. For
      the dimers in the triplet state, nonzero bond dissociation energies are obtained
      which vary from 1.3 kcal/mol for 3Cu2 to 4.6 kcal/mol for 3Au2. Taking into
      account that, in bulky high-spin copper clusters, the bond dissociation energy
      per atom increases steeply to the value of ca. 19 kcal/mol, the results obtained
      in the present paper suggest that the bond dissociation energy per atom in high
      spin gold clusters may reach extremely high values exceeding 20 kcal/mol thus
      becoming comparable to the usual bonding due to the spin-pairing mechanism.

PMID- 18714957
TI  - Theoretical study of gallium nitride molecules, GaN2 and GaN4.
AB  - The electronic and geometric structures of gallium dinitride GaN 2, and gallium
      tetranitride molecules, GaN 4, were systematically studied by employing density
      functional theory and perturbation theory (MP2, MP4) in conjunction with the aug
      cc-pVTZ basis set. In addition, for the ground-state of GaN 4( (2)B 1) a density
      functional theory study was carried out combining different functionals with
      different basis sets. A total of 7 minima have been identified for GaN 2, while
      37 structures were identified for GaN 4 corresponding to minima, transition
      states, and saddle points. We report geometries and dissociation energies for all
      the above structures as well as potential energy profiles, potential energy
      surfaces and bonding mechanisms for some low-lying electronic states of GaN 4.
      The dissociation energy of the ground-state GaN 2 ( X (2)Pi) is 1.1 kcal/mol with
      respect to Ga( (2)P) + N 2( X (1)Sigma g (+)). The ground-state and the first two
      excited minima of GaN 4 are of (2)B 1( C 2 v ), (2)A 1( C 2 v , five member
      ring), and (4)Sigma g (-)( D infinityh ) symmetry, respectively. The dissociation
      energy ( D e) of the ground-state of GaN 4, X (2)B 1, with respect to Ga( (2)P) +
      2 N 2( X (1)Sigma g (+)), is 2.4 kcal/mol, whereas the D e of (4)Sigma g (-) with
      respect to Ga( (4)P) + 2 N 2( X (1)Sigma g (+)) is 17.6 kcal/mol.

PMID- 18714958
TI  - FTIR and Ab initio investigations of the MTBE-water complex.
AB  - The infrared spectrum of methyl tert-butyl ether (MTBE) in liquid water has been
      studied using both FTIR absorption and FTIR-ATR spectroscopy in conjunction with
      ab initio calculations. Compared to the liquid MTBE IR spectrum, the C-O and C-C
      stretching vibrational frequencies of MTBE in water are found to shift to the red
      and blue by up to 26 and 9 cm (-1), respectively. Ab initio calculations suggest
      that these shifts are caused by complexation of the MTBE molecule with water
      molecules through hydrogen bonding. Our observation of the vibrational frequency
      shifts in the IR spectrum of MTBE in water provides the IR spectroscopic evidence
      of organics-water complexes in the diluted aqueous solution. The implication of
      the effect of the hydrogen bond in organics-water complexation on solvation and
      reactivity of the organic compound in aqueous chemical processes is discussed.

PMID- 18714959
TI  - Indium phthalocyanines with different axial ligands: a study of the influence of
      the structure on the photophysics and optical limiting properties.
AB  - The photophysical properties of four axially substituted indium phthalocyanines,
      namely, 2,(3)-tetra- tert-butyl-phthalocyaninato indium chloride ( 1), 2,(3)
      tetra-[(3,5-di- tert-butyl)-phenyloxy]-phthalocyaninato indium bromide ( 2),
      2,(3)-tetra-[(3,5-di- tert-butyl)-phenyloxy]-phthalocyaninato indium iodide ( 3),
      and 2,3-octa-[(2-hexyl)-ethyloxy]-phthalocyaninato indium trifluoroacetate ( 4),
      have been investigated, and their optical limiting properties with nanosecond
      light pulses were evaluated. All complexes behave as reverse saturable absorbers
      in the range of 400-625 nm due to a triplet-triplet excited-state transition.
      Excited-state absorption cross sections and triplet state lifetimes are not
      significantly affected by the nature of the axial ligand. On the other hand,
      remarkable differences in the variation of nonlinear transmittance are observed
      for 1- 4 due to significantly different intersystem crossing rates. Heavier axial
      ligands in phthalocyanines 2 and 3 produce the largest variations of nonlinear
      transmission (heavy-atom effect). Complex 1 in polystyrene matrix shows
      reversible nonlinear absorption when incident fluence does not exceed 0.025 J cm
      (-2).

PMID- 18714960
TI  - Experimental bond critical point and local energy density properties determined
      for Mn-O, Fe-O, and Co-O bonded interactions for tephroite, Mn2SiO4, fayalite,
      Fe2SiO4, and Co2SiO4 olivine and selected organic metal complexes: comparison
      with properties calculated for non-transition and transition metal M-O bonded
      interactions for silicates and oxides.
AB  - Bond critical point (bcp) and local energy density properties for the electron
      density (ED) distributions, calculated with first-principle quantum mechanical
      methods for divalent transition metal Mn-, Co-, and Fe-containing silicates and
      oxides are compared with experimental model ED properties for tephroite, Mn 2SiO
      4, fayalite, Fe 2SiO 4, and Co 2SiO 4 olivine, each determined with high-energy
      synchrotron single-crystal X-ray diffraction data. Trends between the
      experimental bond lengths, R(M-O), (M = Mn, Fe, Co), and the calculated bcp
      properties are comparable with those observed for non-transition M-O bonded
      interactions. The bcp properties, local total energy density, H( r c), and bond
      length trends determined for the Mn-O, Co-O, and Fe-O interactions are also
      comparable. A comparison is also made with model experimental bcp properties
      determined for several Mn-O, Fe-O, and Co-O bonded interactions for selected
      organometallic complexes and several oxides. Despite the complexities of the
      structures of the organometallic complexes, the agreement between the calculated
      and model experimental bcp properties is fair to good in several cases. The G( r
      c)/rho( r c) versus R(M-O) trends established for non-transition metal M-O bonded
      interactions hold for the transition metal M-O bonded interactions with G( r
      c)/rho( r c) increasing in value as H( r c) becomes progressively more negative
      in value, indicating an increasing shared character of the interaction as G( r
      c)/rho( r c) increases in value. As observed for the non-transition metal M-O
      bonded interactions, the Laplacian, nabla (2)rho( r c), increases in value as
      rho( r c) increases and as H( r c) decreases and becomes progressive more
      negative in value. The Mn-O, Fe-O, and Co-O bonded interactions are indicated to
      be of intermediate character with a substantial component of closed-shell
      character compared with Fe-S and Ni-S bonded interactions, which show greater
      shared character based on the | V( r c)|/ G( r c) bond character indicator. The
      atomic charges conferred on the transition metal atoms for the three olivines
      decrease with increasing atomic number from Mn to Fe to Co as the average M-O
      bond lengths decrease from 2.219 to 2.168 to 2.128 A, respectively.

PMID- 18714961
TI  - Infrared signatures of HNO3 and NO3(-) at a model aqueous surface. A theoretical
      study.
AB  - The infrared signatures of nitric acid HNO3 and its conjugate anion NO3(-) at the
      surface of an aqueous layer are derived from electronic structure calculations at
      the HF/SBK+* level of theory on the HNO3 x (H2O)3 --> NO3(-) x H3O(+) x (H2O)2
      model reaction system embedded in clusters comprising 33, 40, 45, and 50
      classical, polarizable waters, mimicking various degrees of solvation [Bianco,
      R.; Wang, S.; Hynes, J. T. J. Phys. Chem. A 2007, 111, 11033]. The molecular
      level character of the various bands is discussed, and the solvation patterns are
      described in terms of hydrogen bonding and resulting polarization of the species'
      intramolecular bonds. Connection is made with assorted experimental results,
      including surface-sensitive Sum Frequency Generation spectroscopy of aqueous
      nitric acid solutions, infrared spectroscopy of amorphous thin films of nitric
      acid monohydrate (NAM) and dihydrate (NAD), and infrared and Raman spectroscopic
      results for bulk aqueous solutions of nitric acid and nitrate salts.

PMID- 18714962
TI  - Computational study on nonenzymatic peptide bond cleavage at asparagine and
      aspartic acid.
AB  - Nonenzymatic peptide bond cleavage at asparagine (Asn) and glutamine (Gln)
      residues has been observed during peptide deamidation experiments; cleavage has
      also been reported at aspartic acid (Asp) and glutamic acid (Glu) residues.
      Although peptide backbone cleavage at Asn is known to be slower than deamidation,
      fragmentation products are often observed during peptide deamidation experiments.
      In this study, mechanisms leading to the cleavage of the carboxyl-side peptide
      bond of Asn and Asp residues were investigated using computational methods
      (B3LYP/6-31+G**). Single-point solvent calculations at the B3LYP/6-31++G** level
      were carried out in water, utilizing the integral equation formalism-polarizable
      continuum (IEF-PCM) model. Mechanism and energetics of peptide fragmentation at
      Asn were comparatively analyzed with previous calculations on deamidation of Asn.
      When deamidation proceeds through direct hydrolysis of the Asn side chain or
      through cyclic imide formationvia a tautomerization routeit exhibits lower
      activation barriers than peptide bond cleavage at Asn. The fundamental
      distinction between the mechanisms leading to deamidationvia a succinimideand
      backbone cleavage was found to be the difference in nucleophilic entities
      involved in the cyclization process (backbone versus side-chain amide nitrogen).
      If deamidation is prevented by protein three-dimensional structure, cleavage may
      become a competing pathway. Fragmentation of the peptide backbone at Asp was also
      computationally studied to understand the likelihood of Asn deamidation preceding
      backbone cleavage. The activation barrier for backbone cleavage at Asp residues
      is much lower (approximately 10 kcal/mol) than that at Asn. This suggests that
      peptide bond cleavage at Asn residues is more likely to take place after it has
      deamidated into Asp.

PMID- 18714963
TI  - Kinetics and mechanism of oxidation of N, N'-dimethylaminoiminomethanesulfinic
      acid by acidic bromate.
AB  - The major metabolites of the physiologically active compound dimethylthiourea
      (DMTU), dimethylaminoiminomethansesulfinic acid (DMAIMSA), and
      dimethylaminoiminomethanesulfonic acid (DMAIMSOA) were synthesized, and their
      kinetics and mechanisms of oxidation by acidic bromate and aqueous bromine was
      determined. The oxidation of DMAIMSA is much more facile and rapid as compared to
      a comparable oxidation by the same reagents of the parent compound, DMTU. The
      stoichiometry of the bromate-DMAIMSA reaction was determined to be 2BrO 3 (-) +
      3NHCH 3(NCH 3)CSO 2H + 3H 2O --> 3SO 4 (2) (-) + 2Br (-) + 3CO(NHCH 3) 2 + 6H
      (+), with quantitative formation of sulfate. In excess bromate conditions, the
      stoichiometry was 4BrO 3 (-) + 5NHCH 3(NCH 3)CSO 2H + 3H 2O --> 5SO 4 (2) (-) +
      2Br 2 + 5CO(NHCH 3) 2 + 6H (+). The direct bromine-DMAIMSA reaction gave an
      expected stoichiometric ratio of 2:1 with no further oxidation of product
      dimethylurea (DMU) by aqueous bromine. The bromine-DMAIMSA reaction was so fast
      that it was close to diffusion-controlled. Excess bromate conditions delivered a
      clock reaction behavior with the formation of bromine after an initial quiescent
      period. DMAIMSOA, on the other hand, was extremely inert to further oxidation in
      the acidic conditions used for this study. Rate of consumption of DMAIMSA showed
      a sigmoidal autocatalytic decay. The postulated mechanism involves an initial
      autocatalytic build-up of bromide that fuels the formation of the reactive
      oxidizing species HBrO 2 and HOBr through standard oxybromine reactions. The long
      and weak C-S bond in DMAIMSA ensures that its oxidation goes directly to DMU and
      sulfate, bypassing inert DMAIMSOA.

PMID- 18714965
TI  - Orthogonal projections to latent structures discriminant analysis modeling on in
      situ FT-IR spectral imaging of liver tissue for identifying sources of
      variability.
AB  - In this study, the orthogonal projections to latent structures discriminant
      analysis (OPLS-DA) method was used to assess the in situ chemical composition of
      two different cell types in mouse liver samples, hepatocytes and erythrocytes.
      High spatial resolution FT-IR microspectroscopy equipped with a focal plan array
      (FPA) detector is capable of simultaneously recording over 4000 spectra from 64 x
      64 pixels with a maximum spatial resolution of about 5 microm x 5 microm, which
      allows for the differentiation of individual cells. The main benefit with OPLS-DA
      lies in the ability to separate predictive variation (between cell type) from
      variation that is uncorrelated to cell type in order to facilitate understanding
      of different sources of variation. OPLS-DA was able to differentiate between
      chemical properties and physical properties (e.g., edge effects). OPLS-DA model
      interpretation of the chemical features that separated the two cell types clearly
      highlighted proteins and lipids/bile acids. The modeled variation that was
      uncorrelated to cell type made up a larger portion of the total variation and
      displayed strong variability in the amide I region. This could be traced back to
      a gradient in the high intensity (high-density) areas vs the low intensity areas
      (close to empty areas) that as a result of normalization had an adverse effect on
      FT-IR spectral profiles. This highlights that OPLS-DA provides an effective
      solution to identify different sources of variability, both predictive and
      uncorrelated, and also facilitates understanding of any sampling, experimental,
      or preprocessing issues.

PMID- 18714964
TI  - Fluorinated xerogel-derived microelectrodes for amperometric nitric oxide
      sensing.
AB  - An amperometric fluorinated xerogel-derived nitric oxide (NO) microelectrode is
      described. A range of fluorine-modified xerogel polymers were synthesized via the
      cohydrolysis and condensation of alkylalkoxy- and fluoroalkoxysilanes. Such
      polymers were evaluated as NO sensor membranes to identify the optimum
      composition for maximizing NO permeability while providing sufficient selectivity
      for NO in the presence of common interfering species. By taking advantage of both
      the versatility of sol-gel chemistry and the "poly(tetrafluoroethylene)-like"
      high NO permselective properties of the xerogels, the performance of the
      fluorinated xerogel-derived sensors was excellent, surpassing all miniaturized NO
      sensors reported to date. In contrast to previous electrochemical NO sensor
      designs, xerogel-based NO microsensors were fabricated using a simple, reliable
      dip-coating procedure. An optimal permselective membrane was achieved by
      synthesizing xerogels of methyltrimethoxysilane (MTMOS) and 20% (heptadecafluoro
      1,1,2,2-tetrahydrodecyl)trimethoxysilane (17FTMS, balance MTMOS) under acid
      catalyzed conditions. The resulting NO microelectrode had a conical tip of
      approximately 20 microm in diameter and approximately 55 microm in length and
      exhibited sensitivities of 7.91 pA x nM (-1) from 0.2 to 3.0 nM (R (2) = 0.9947)
      and 7.60 nA x microM (-1) from 0.5 to 4.0 microM ( R (2) = 0.9999), detection
      limit of 83 pM (S/ N = 3), response time ( t 95%) of <3 s, and selectivity (log K
      NO, j (amp)) of -5.74, <-6, <-6, <-6, <-6, -5.84, and -1.33 for j = nitrite,
      ascorbic acid, uric acid, acetaminophen, dopamine, ammonia/ammonium, and carbon
      monoxide. In addition, the sensor proved functional up to 20 d, maintaining
      >or=90% of the sensor's initial sensitivity without serious deterioration in
      selectivity.

PMID- 18714966
TI  - Direct determination of trace elements in powdered samples by in-cell isotope
      dilution femtosecond laser ablation ICPMS.
AB  - A method has been developed for the direct and simultaneous multielement
      determination of Cu, Zn, Sn, and Pb in soil and sediment samples using
      femtosecond laser ablation inductively coupled plasma mass spectrometry (fs-LA
      ICPMS) in combination with isotope dilution mass spectrometry (IDMS). The in-cell
      isotope dilution fs-LA-ICPMS method proposed in this work was based on the quasi
      simultaneous ablation of the natural abundance sample and the isotopically
      enriched solid spike, which was performed using a high repetition rate laser and
      a fast scanning beam device in a combined manner. Both the sample preparation
      procedure and the total analysis time have been drastically reduced, in
      comparison with previous approaches, since a unique multielement isotopically
      enriched solid spike was employed to analyze different powdered samples. Numerous
      experimental parameters were carefully selected (e.g., carrier gas flow rate,
      inlet diameter of the ablation cell, sample translation speed, scanner speed,
      etc.) in order to ensure the complete mixing between the sample and the solid
      spike aerosols. The proposed in-cell fs-LA-ICP-IDMS method was tested for the
      analysis of two soil (CRM 142R, GBW-07405) and two sediment (PACS-2, IAEA-405)
      reference materials, and the analysis of Cu, Zn, Sn, and Pb yielded good
      agreement of usually not more than 10% deviation from the certified values and
      precisions of less than 15% relative standard deviation. Furthermore, the
      concentrations were in agreement not only with the certified values but also with
      those obtained by ICP-IDMS after the microwave-assisted digestion of the solid
      samples, demonstrating therefore that in-cell fs-LA-ICP-IDMS opens the
      possibility for accurate and precise determinations of trace elements in powdered
      samples reducing the total sample preparation time to less than 5 min.
      Additionally, scanning electron microscope measurements showed that the aerosol
      generated by in-cell fs-LA-ICP-IDMS predominantly consisted of linear
      agglomerates of small particles (in the order of few tens of nanometers) and a
      few large spherical particles with diameters below 225 nm.

PMID- 18714967
TI  - Method for simultaneous oxygen and hydrogen isotope analysis of water of
      crystallization in hydrated minerals.
AB  - The isotopic composition of water in hydrated minerals, such as gypsum and
      jarosite, has numerous applications in studies of recent climate change, ore
      formation, and soil development. However, oxygen and hydrogen isotope analysis of
      water of crystallization is currently a complex procedure. Commonly used
      techniques involve offline extraction of water from hydrated minerals and
      subsequent isotope analysis. Such methods are time-consuming, require relatively
      large sample sizes, and the stepwise procedure has to be carried out with extreme
      caution to avoid erroneous results. We present a novel online method for the
      oxygen and hydrogen isotope analysis of water of crystallization in hydrous
      minerals. Gypsum (CaSO 4.2H 2O) samples, 2 mg in size, are reacted in a simply
      modified carbon reducing furnace connected to a continuous-flow mass spectrometer
      system. Analysis time is less than 10 min/sample. The precision (2 std dev mean)
      of our method for 2-mg gypsum (30 mumol of H 2O) samples is 0.3 per thousand for
      oxygen and less than 1.4 per thousand for hydrogen isotope measurements. For
      oxygen isotope analysis alone, samples as small as 0.2 mg of gypsum can be
      analyzed with a precision of 0.3 per thousand.

PMID- 18714968
TI  - Alkali metal ion binding to glutamine and glutamine derivatives investigated by
      infrared action spectroscopy and theory.
AB  - The gas-phase structures of alkali-metal cationized glutamine are investigated by
      using both infrared multiple photon dissociation (IRMPD) action spectroscopy,
      utilizing light generated by a free electron laser, and theory. The IRMPD spectra
      contain many similarities that are most consistent with glutamine adopting
      nonzwitterionic forms in all ions, but differences in the spectra indicate that
      the specific nonzwitterionic forms adopted depend on metal-ion identity. For ions
      containing small alkali metals, the metal ion is solvated predominantly by the
      amino group, the carbonyl oxygen of the carboxylic acid group, and the carbonyl
      oxygen of the amide group. With increasing alkali-metal-ion size, additional
      structures are present in which the carboxylic acid group donates a hydrogen bond
      to the amino group and the metal ion is solvated only by the amide and carboxylic
      acid groups. The effects of alkylation of the amino and amide groups on the
      proton affinity of isolated glutamine and the relative zwitterion stability of
      sodiated glutamine were examined computationally. Methylation of the amino group
      increases the proton affinity of isolated glutamine and preferentially stabilizes
      the zwitterionic form of sodiated glutamine by roughly 20 kJ/mol. Ethylation and
      isopropylation of the amide group each increase the proton affinity of isolated
      glutamine by roughly 13 kJ/mol but preferentially stabilize the zwitterionic form
      of sodiated glutamine by less than 3 kJ/mol. These results indicate that effects
      of proton affinity on relative zwitterion stability compete with effects of metal
      ion solvation.

PMID- 18714969
TI  - Detailed dynamics of the nonradiative deactivation of adenine: a semiclassical
      dynamics study.
AB  - A realistic dynamics simulation study is reported for the ultrafast radiationless
      deactivation of 9H-adenine. The simulation follows two different excitations
      induced by two 80 fs (fwhm) laser pulses that are different in energy: one has a
      photon energy of 5.0 eV, and the other has a photon energy of 4.8 eV. The
      simulation shows that the excited molecule decays to the electronic ground state
      from the (1)pipi* state in both excitations but through two different
      radiationless pathways: in the 5.0 eV excitation, the decay channel involves the
      out-of-plane vibration of the amino group, whereas in the 4.8 eV excitation, the
      decay strongly associates with the deformation of the pyrimidine at the C 2 atom.
      The lifetime of the (1) npi* state determined in the simulation study is 630 fs
      for the 5.0 eV excitation and 1120 fs for the 4.8 eV excitation. These are
      consistent with the experimental values of 750 and 1000 fs. We conclude that the
      experimentally observed difference in the lifetime of the (1) npi* state at
      various excitations results from the different radiationless deactivation
      pathways of the excited molecule to the electronic ground state.

PMID- 18714970
TI  - CO coordination at XNi4 clusters with impurities X = H, C, O. A density
      functional study.
AB  - We report a computational investigation of CO adsorption on small nickel clusters
      that contain single impurity atoms H, C, or O. At bare Ni 4 and clusters with H
      or O impurity, the most stable coordination of the probe molecule is on top of a
      Ni atom which interacts with the impurity. The CNi 4 cluster is an exception
      where 3-fold coordination of CO was determined to be more stable than that on
      top, however, by 4 kJ/mol only. Our results suggest that the heteroatoms X (X =
      H, C, O) affect only weakly the reactivity of the cluster with respect to CO; the
      binding energy of CO in the most stable complexes (CO)XNi 4 increases at most by
      10% compared to the value for bare Ni 4, 194 kJ/mol. The impurity induces a small
      decrease of the CO infrared frequency shift for on-top coordinated CO, compared
      to Ni 4, because of partial oxidation of the metal moiety. A notable difference
      is predicted for clusters that contain a C impurity because of the different
      preferred coordination mode which results in a strong CO frequency red shift of
      approximately 300 cm (-1). The calculated characteristic CO frequency shifts may
      be helpful in identifying experimentally clusters with impurity atoms.

PMID- 18714971
TI  - Investigations of silicon-nitrogen hydrides from reaction of nitrogen atoms with
      silane: experiments and calculations.
AB  - Using a quadrupole mass filter and vacuum-ultraviolet ionization, we measured the
      time-of-flight spectra of species at mass-to-charge ratios of m/ z = 45-42 from
      the reaction of N + SiH 4 in crossed molecular beams. Species with m/ z = 44 and
      43 correspond to reaction products HSiNH/SiNH 2 and HSiN/HNSi, respectively;
      species with m/ z = 45 and 42 are assigned to isotopic variants and daughter
      ions, respectively, of those two reaction products. We measured the
      photoionization yields and branching ratios for dissociative ionization of
      reaction products as a function of photoionization energy. The ionization
      thresholds of products HSiNH/SiNH 2 and HSiN/HNSi were determined to be 6.7 and
      9.2 eV, respectively. Furthermore, we calculated the equilibrium structures,
      electronic energies, and vibrational wavenumbers of various silicon-nitrogen
      hydrides H x SiNH y ( x + y = 0-3) using quantum-chemical methods. SiNH 2 (X (2)B
      2) and HNSi (X (1)Sigma (+)) are more stable than HSiNH (X (2)A') and HSiN (X
      (1)Sigma (+)) by 0.82 and 2.81 eV, respectively. SiNH 2 (X (2)B 2), HSiNH (X
      (2)A'), HNSi (X (1)Sigma (+)), and HSiN (X (1)Sigma (+)) have adiabatic
      ionization energies of 6.81, 8.19, 10.21, and 10.23 eV, respectively. These
      experimental and calculated results indicate that SiNH 2 (X (2)B 2) and HNSi (X
      (1)Sigma (+)) are dominant among isomeric products in the reaction of N + SiH 4.
      This work presents the first observation of products from the reaction of N + SiH
      4 in crossed beams and extensive calculations on pertinent silicon-nitrogen
      hydrides.

PMID- 18714972
TI  - Singlet-triplet energy splitting and excited states of phenylnitrene.
AB  - The vertical and adiabatic singlet-triplet energy splittings (Delta E ST) of
      phenylnitrene were computed by a variety of multireference configuration
      interaction and perturbation theory methods employing basis sets of up to
      quadruple-xi quality and extrapolation to the complete basis set limit. The
      vertical and adiabatic energy gaps are 18.9 and 15.9 kcal mol (-1), respectively,
      the latter in reasonable agreement with the revised experimental value of 15.1 +/
      0.2 kcal mol (-1). The energy difference between both states at the geometry of
      the a (1)A 2 singlet state was also considered and amounts to 13.8 kcal mol (-1).
      In obtaining accurate state energy splittings, basis set completeness turns out
      to be a more important issue than the level of dynamical electron correlation
      treatment. Density functional theory that is frequently employed to investigate
      phenylnitrenes and their rearrangements yields varying results and, depending on
      the functional, gives adiabatic energy differences between 9 and 16 kcal mol (
      1). The b (1)A 1 state has a similar geometry as the ground state of 1 and is 31
      kcal mol (-1) higher in energy. According to best estimates, the next higher
      singlet states, c (1)A 1 and d (1)B 1, are 57 and 72 kcal mol (-1) above the
      ground state. In the triplet manifold, vertical excitation energies to the A (3)B
      1 and B (3)A 2 states are 71 and 77 kcal mol (-1), respectively.

PMID- 18714973
TI  - The addition reaction between silylene and ethyne: further isotope studies,
      pressure dependence studies, and quantum chemical calculations.
AB  - Time-resolved kinetic studies of the reaction of dideutero-silylene, SiD 2,
      generated by laser flash photolysis of phenylsilane-d 3, have been carried out to
      obtain rate constants for its bimolecular reaction with C 2H 2. The reaction was
      studied in the gas phase over the pressure range 1-100 Torr in SF 6 bath gas, at
      five temperatures in the range 297-600 K. The second-order rate constants
      obtained by extrapolation to the high-pressure limits at each temperature fitted
      the Arrhenius equation log( k (infinity)/cm (3) molecule (-1) s (-1)) = (-10.05
      +/- 0.05) + (3.43 +/- 0.36 kJ mol (-1))/ RT ln 10. The rate constants were used
      to obtain a comprehensive set of isotope effects by comparison with earlier
      obtained rate constants for the reactions of SiH 2 with C 2H 2 and C 2D 2.
      Additionally, pressure-dependent rate constants for the reaction of SiH 2 with C
      2H 2 in the presence of He (1-100 Torr) were obtained at 300, 399, and 613 K.
      Quantum chemical (ab initio) calculations of the SiC 2H 4 reaction system at the
      G3 level support the initial formation of silirene, which rapidly isomerizes to
      ethynylsilane as the major pathway. Reversible formation of vinylsilylene is also
      an important process. The calculations also indicate the involvement of several
      other intermediates, not previously suggested in the mechanism. RRKM calculations
      are in semiquantitative agreement with the pressure dependences and isotope
      effects suggested by the ab initio calculations, but residual discrepancies
      suggest the possible involvement of the minor reaction channel, SiH 2 + C 2H 2 -
      > Si( (3)P 1) + C 2H 4. The results are compared and contrasted with previous
      studies of this reaction system.

PMID- 18714974
TI  - Prochiral and chiral resolution in 2H NMR spectra: solutes in stretched and
      compressed gelatin gels.
AB  - We demonstrate prochiral and chiral spectral resolution using residual (2)H NMR
      quadrupolar splittings over a wide range of anisotropic conditions in liquid
      samples. We use a reversible gel-stretching/compressing device in a conventional
      high-field NMR spectrometer. We show the stability of gelatin gels as well as
      their unique ability to switch between multiple stretched and compressed states,
      thus also changing the sign of residual dipolar couplings in (1)H and (13)C NMR.
      This flexibility will be important for resolving spectra of mixtures of other
      chiral compounds and for structure determination of selected peptides.

PMID- 18714975
TI  - The key role of solvation dynamics in intramolecular electron transfer: time
      resolved photophysics of crystal violet lactone.
AB  - The intramolecular electron-transfer reaction in crystal violet lactone in polar
      aprotic solvents is studied with femtosecond transient absorption spectroscopy.
      The initially excited charge transfer state (1)CT A is rapidly converted into a
      highly polar charge transfer state (1)CT B. This ultrafast electron transfer is
      seen as a solvent-dependent dual fluorescence in steady-state spectra. We find
      that the electron-transfer process can be followed by a change from a double
      peaked transient absorption spectrum to a single-peak one in the low picosecond
      range. The transient absorption kinetic curves are multiexponential, and the
      fitted time constants are solvent dependent but do not reproduce the known
      solvation times. For 6-dimethylaminophthalide, the optically active constituent
      of crystal violet lactone, only a small temporal evolution of the spectra is
      found. To explain these findings, we present a model that invokes a time
      dependent electron-transfer rate. The rate is determined by the instantaneous
      separation of the two charge-transfer states. Because of their differing dipole
      moments, they are dynamically lowered to a different extent by the solvation.
      When they temporarily become isoenergetic, equal forward and backward transfer
      rates are reached. The intrinsic electron-transfer ( (1)CT A --> (1)CT B)
      reaction is probably as fast as that in the structurally analogous malachite
      green lactone (on the 100 fs time scale). The key element for the dynamics is
      therefore its control by the solvent, which changes the relative energetics of
      the two states during the solvation process. With further stabilization of the
      more polar state, the final equilibrium in state population is reached.

PMID- 18714976
TI  - Donator acceptor map for carotenoids, melatonin and vitamins.
AB  - Bright yellow and red colors in animals and plants are assumed to be caused by
      carotenoids (CAR). In animals, these pigments are deposited in scales, skin and
      feathers. Together with other naturally occurring and colorless substances such
      as melatonin and vitamins, they are considered antioxidants due to their free
      radical-scavenging properties. However, it would be better to refer to them as
      "antiradicals", an action that can take place either donating or accepting
      electrons. In this work we present quantum chemical calculations for several CAR
      and some colorless antioxidants, such as melatonin and vitamins A, C and E. The
      antiradical capacity of these substances is determined using vertical ionization
      energy (I), electron affinity (A), the electrodonating power (omega(-)) and the
      electroaccepting power (omega(+)). Using fluor and sodium as references, electron
      acceptance (R(a)) and electron donation (R(d)) indexes are defined. A plot of
      R(d) vs R(a) provides a donator acceptor map (DAM) useful to classify any
      substance regarding its electron donating-accepting capability. Using this DAM, a
      qualitative comparison among all the studied compounds is presented. According to
      R(d) values, vitamin E is the most effective antiradical in terms of its electron
      donor capacity, while the most effective antiradical in terms of its electron
      acceptor capacity, R(a), is astaxanthin, the reddest CAR. These results may be
      helpful for understanding the role played by naturally occurring pigments, acting
      as radical scavengers either donating or accepting electrons.

PMID- 18714977
TI  - Matrix infrared spectroscopic and theoretical studies on the reactions of early
      lanthanoid atoms with nitrous oxide in excess argon.
AB  - Reactions of laser-ablated early lanthanoid atoms (Ce, Pr, Nd, Sm, and Eu, except
      for radioactive Pm) with N 2O molecules in excess argon have been investigated
      using matrix-isolation infrared spectroscopy. Lanthanoid monoxide-dinitrogen
      complexes, OLn(N 2) (Ln = Ce, Pr, Nd, and Sm), are observed during sample
      deposition and identified on the basis of isotopic shifts, mixed isotopic
      splitting patterns, and CCl 4-doping experiments, whereas no new product is
      observed for Eu. The OLnNN (+) (Ln = Ce, Pr, Nd, and Sm) cations appear during
      sample deposition and increase visibly upon broadband irradiation (lambda > 250
      nm) at the expense of the neutral OLn(N 2) complexes. Density functional theory
      calculations have been performed on the new products, which support
      identification of the OLn(N 2) and OLnNN (+) complexes from the matrix infrared
      spectra.

PMID- 18714978
TI  - Discovery of novel Cdc25 phosphatase inhibitors with micromolar activity based on
      the structure-based virtual screening.
AB  - Cdc25 phosphatases have been considered as attractive drug targets for anticancer
      therapy because of the correlation of their overexpression with a wide variety of
      cancers. We have been able to identify five novel Cdc25 phosphatase inhibitors
      with micromolar activity by means of a computer-aided drug design protocol
      involving the homology modeling of Cdc25A and the virtual screening with the
      automated AutoDock program implementing the effects of ligand solvation in the
      scoring function. Because the newly discovered inhibitors are structurally
      diverse and reveal a significant potency with IC 50 values lower than 10 microM,
      they can be considered for further development by structure-activity relationship
      studies or de novo design methods. The differences in binding modes of the
      identified inhibitors in the active sites of Cdc25A and B are discussed in
      detail.

PMID- 18714979
TI  - Novel insight in structure-activity relationship and bioanalysis of P
      glycoprotein targeting highly potent tetrakishydroxymethyl substituted 3,9
      diazatetraasteranes.
AB  - Novel 3,9-diazatetraasteranes have been synthesized with varied aromatic
      substitution patterns and evaluated as P-glycoprotein (P-gp) inhibitors.
      Structure-activity relationships (SAR) are discussed in relation to determined
      physicochemical properties. The potential to induce P-gp expression has been
      evaluated in cancer cell lines. The bioanalytical results indicate favorable
      noninducing properties compared to P-gp inducing drug standard.

PMID- 18714980
TI  - Discovery of antimycobacterial spiro-piperidin-4-ones: an atom economic,
      stereoselective synthesis, and biological intervention.
AB  - An atom economic and stereoselective synthesis of several spiro-piperidin-4-ones
      through 1,3-dipolar cycloaddition of azomethine ylides generated in situ from
      isatin and alpha-amino acids viz . proline, phenylglycine, and sarcosine to a
      series of 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones is
      described. These compounds were evaluated for their in vitro and in vivo activity
      against Mycobacterium tuberculosis H37Rv (MTB), multidrug resistant Mycobacterium
      tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC(2)). Compound 4-(4
      fluorophenyl)-5-phenylpyrrolo(spiro[2.3'']oxindole)spiro[3.3']-1'-methyl-5'-(4
      fluorophenylmethylidene)piperidin-4'-one (4e) was found to be the most active in
      vitro with a MIC value of 0.07 microM against MTB and was 5.1 and 67.2 times more
      potent than isoniazid and ciprofloxacin, respectively. In vivo, compound 4e
      decreased the bacterial load in lung and spleen tissues with 1.30 and 3.73-log 10
      protections respectively and was considered to be promising in reducing bacterial
      count in lung and spleen tissues.

PMID- 18714981
TI  - Phosphate prodrugs derived from N-acetylglucosamine have enhanced
      chondroprotective activity in explant cultures and represent a new lead in
      antiosteoarthritis drug discovery.
AB  - We report the application of the phosphoramidate ProTide approach, developed by
      us for antiviral nucleosides, to sugar derivatives with potential
      chondroprotection against osteoarthritis. In particular, N-acetylglucosamine was
      converted to a series of 06 arylaminoacyl phosphoramidates with ester and amino
      acid variation. Compounds were prepared by two routes, with or without sugar
      protection, and were isolated as phosphate diastereoisomers. The compounds were
      assayed for cellular toxicity and for inhibition of IL-1 induced
      glycosaminoglycan (GAG) release (i.e., proteoglycan degradation) from bovine
      articular cartilage in vitro explant cultures. By comparison to the N-acetyl
      glucosamine parent, some of the analogues show a significant enhancement in
      efficacy in the inhibition of inflammatory cytokine-induced proteoglycan
      degradation.

PMID- 18714982
TI  - Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective
      dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage
      kinase 1 crystallography, and oral in vivo activity in 1-methyl-4
      phenyltetrahydropyridine models.
AB  - The optimization of the dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-one R(2)
      and R(12) positions led to the identification of the first MLK1 and MLK3 subtype
      selective inhibitors within the MLK family. Compounds 14 (CEP-5104) and 16 (CEP
      6331) displayed good potency for MLK1 and MLK3 inhibition with a greater than 30-
      to 100-fold selectivity for related family members MLK2 and DLK. Compounds 14 and
      16 were orally active in vivo in a mouse MPTP biochemical efficacy model that was
      comparable to the first-generation pan-MLK inhibitor 1 (CEP-1347). The MLK1
      structure-activity relationships were supported by the first-reported X-ray
      crystal structure of MLK1 bound with 16.

PMID- 18714984
TI  - Linking number analysis of a pentadecanuclear metallamacrocycle: a Mobius-Craig
      system revealed.
AB  - An analysis of the pi-electronic topology of a recently reported pentadecanuclear
      manganese metallacycle in terms of linking number, twist, and writhe confirms its
      previous assignment as a Mobius system of order six. The total degree of local
      torsion is reduced by a significant contribution from writhe, thus correcting the
      previously inferred local torsion at each metal center from 120 degrees to
      approximately 90 degrees . This latter value suggests a model for the cyclic pi
      conjugation around the metallacycle, which involves 3d pi-2p pi interactions at
      the metal center, of a type first suggested by Craig 50 years ago in the context
      of main group cyclic aromatic systems.

PMID- 18714983
TI  - Physicochemical properties of the high-field MRI-relevant [Gd(DTTA-Me)(H2O)2]-
      complex.
AB  - To study the physicochemical properties of the DTTA chelating moiety (H4DTTA =
      diethylenetriaminetetraacetic acid = N,N'-[iminobis(ethane-2,1-diyl)]bis[N
      (carboxymethyl)glycine]), used in several compounds proposed as magnetic
      resonance imaging (MRI) contrast agents, the methylated derivative H4DTTA-Me
      (N,N'-[(methylimino)bis(ethane-2,1-diyl)]bis[N-(carboxymethyl)glycine]) was
      synthesized. Protonation constants of the ligand were determined in an aqueous
      solution by potentimetry and (1)H NMR pH titration and compared to various DTTA
      derivatives. Stability constants were measured for the chelates formed with
      Gd(3+) (log K(GdL) = 18.60 +/- 0.10) and Zn(2+) (log K(ZnL) = 17.69 +/- 0.10). A
      novel approach of determining the relative conditional stability constant of two
      paramagnetic complexes in a direct way by (1)H NMR relaxometry is presented and
      was used for the Gd(3+) complexes [Gd(DTTA-Me)(H2O)2](-) (L1) and [Gd(DTPA
      BMA)(H2O)] (L2) [K(L1/L2)*(at pH 8.3, 25 degrees C) = 6.4 +/- 0.3]. The
      transmetalation reaction of the Gd(3+) complex with Zn(2+) in a phosphate buffer
      solution (pH 7.0) was measured to be twice as fast for [Gd(DTTA-Me)(H2O)2](-) in
      comparison to that for [Gd(DTPA-BMA)(H2O)]. This can be rationalized by the
      higher affinity of Zn(2+) toward DTTA-Me(4-) if compared to DTPA-BMA(3-). The
      formation of a ternary complex with L-lactate, which is common for DO3A-based
      heptadentate complexes, has not been observed for [Gd(DTTA-Me)(H2O)2](-) as
      monitored by (1)H NMR relaxometric titrations. From the results, it was concluded
      that the heptadentate DTTA-Me(4-) behaves similarly to the commercial octadentate
      DTPA-BMA(3-) with respect to stability. The use of [Gd(DTTA-Me)(H2O)2](-) as an
      MRI contrast agent in vitro and in animal studies is conceivable, mainly at high
      magnetic fields, where an increase of the inner-sphere-coordination water
      actually seems to be the most certain way to increase the relaxivity.

PMID- 18714985
TI  - Hydration properties of aqueous Pb(II) ion.
AB  - Using density functional theory and polarized continuum models, we have
      determined the most probable coordination number and structure of the first
      hydration shell of aqueous Pb(II). The geometries and hydration free energies of
      Pb(H2O)(1-9)(2+) were examined and benchmarked against experimental values. The
      free energies of hydration of Pb(H2O)(6-8)(2+) were found to match the
      experimental value within 10 kcal/mol. Moreover, based upon our thermochemical
      results for single water addition, primary hydration numbers of 6, 7, and 8 are
      all thermally accessible at STP. Use of a small-core 60 electron effective core
      potential (ECP) with the aug-cc-pvdz-PP basis on Pb resulted in structures that
      are significantly less hemidirected than predicted when using the large-core 78
      electron ECP and the lanl2DZ basis on the metal. Our results imply that the hemi-
      to holo-directed transition in Pb(II)-water complexes is driven by coordination
      number and not hybridization of the 6s lone-pair orbital or enhanced covalent
      bonding in the Pb-OH2 bond. In addition to basis set effects, the influence of
      different solvation models on hydration reactions has further been examined so as
      to determine the relative accuracy of the calculated hydration thermochemistry.

PMID- 18714986
TI  - Interaction of mixed-donor macrocycles containing the 1,10-phenanthroline subunit
      with selected transition and post-transition metal ions: metal ion recognition in
      competitive liquid-liquid solvent extraction of Cu(II), Zn(II), Pb(II), Cd(II),
      Ag(I), and Hg(II).
AB  - Two new mixed aza-thia crowns 5-aza-2,8-dithia[9]-(2,9)-1,10-phenanthrolinophane
      (L(4)) and 2,8-diaza-5-thia[9]-(2,9)-1,10-phenanthrolinophane (L(7)) have been
      synthesized and characterized. The coordination behavior of L(4) and L(7) toward
      the metal ions Cu(II), Zn(II), Pb(II), Cd(II), Hg(II), and Ag(I) was studied in
      aqueous solution by potentiometric methods, in CD3CN/D2O 4:1 (v/v) by (1)H NMR
      titrations and in the solid state. The data obtained were compared with those
      available for the coordination behavior toward the same metal ions of
      structurally analogous mixed donor macrocyclic ligands L(1)-L(3), L(5), L(6): all
      these contain a phenanthroline subunit but have only S/O/N(aromatic) donor groups
      in the remaining portion of the ring and are, therefore, less water-soluble than
      L(4) and L(7). The complexes [Cd(NO3)2(L(5))], [Pb(L(7))](ClO4)2 x 1/2MeCN,
      [Pb(L(4))](ClO4)2 x MeCN, and [Cu(L(7))](ClO4)2 x 3/2MeNO2 were characterized by
      X-ray crystallography. The efficacy of L(1)-L(7) in competitive liquid-liquid
      metal ion extraction of Cu(II), Zn(II), Cd(II), Pb(II), Ag(I), and Hg(II) was
      assessed. In the absence of Hg(II), a clear extraction selectivity for Ag(I) was
      observed in all systems investigated.

PMID- 18714987
TI  - One-, two-, and three-dimensional arrays of Eu3+-4,4,5,5,5-pentafluoro-1
      (naphthalen-2-yl)pentane-1,3-dione complexes: synthesis, crystal structure and
      photophysical properties.
AB  - A novel beta-diketone, 4,4,5,5,5-pentafluoro-1-(naphthalen-2-yl)pentane-1,3-dione
      (HPFNP), which contains polyfluorinated alkyl group, as well as the long
      conjugated naphthyl group, has been used for the synthesis of a series of new
      tris(beta-diketonate)europium(III) complexes of the general formula Eu(PFNP)3 x L
      [where L = H2O, 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 4,7-diphenyl
      1,10-phenanthroline (bath)] and characterized by various spectroscopic
      techniques. The single-crystal X-ray diffraction analysis of Eu(PFNP) 3.bpy
      revealed that the complex is mononuclear, the central Eu(3+) ion is coordinated
      by six oxygen atoms furnished by three beta-diketonate ligands, and two nitrogen
      atoms from a bidentate bipyridyl ligand, in an overall distorted square prismatic
      geometry. Further, analysis of the X-ray crystal data of the above complex also
      revealed interesting 1D, 2D, and 3D networks based on intra- and intermolecular
      hydrogen bonds. The room-temperature PL spectra of the complexes are composed of
      typical Eu(3+) red emissions, assigned to transitions between the first excited
      state ((5)D0) and the multiplet ((7)F(0-4)). The results demonstrate that the
      substitution of solvent molecules by bidentate nitrogen ligands in Eu(PFNP)3 x
      H2O x EtOH greatly enhances the quantum yields and lifetime values.

PMID- 18714988
TI  - Selective metal substitution for the preparation of heterobimetallic microporous
      coordination polymers.
AB  - The designed synthesis of heterobimetallic microporous coordination polymers
      (MCPs) is reported by a strategy employing the selective replacement of a single
      metal in homometallic MCPs with two unique metal coordination environments:
      octahedral and tetrahedral. This strategy is successful in the preparation of six
      mixed-metal MCPs, where Co/Zn and Ni/Zn versions of MOF-4, MOF-39, and a Zn-BTEC
      MCP are reported.

PMID- 18714989
TI  - Low-valent molecular plutonium halide complexes.
AB  - Treatment of plutonium metal with 1.5 equiv of bromine in tetrahydrofuran (thf)
      led to isolation of PuBr3(thf)4 (1), which is a new versatile synthon for
      exploration of non-aqueous Pu(III) chemistry. Adventitious water in the system
      resulted in structural characterization of the eight-coordinate complex
      [PuBr2(H2O)6][Br] (2). The crystal structure of PuI3(thf)4 (3) has been
      determined for the first time and is isostructural with UI3(thf)4. Attempts to
      form a bis(imido) plutonyl(VI) moiety ([Pu(NR)2](2+)) by oxidation of PuI3(py)4
      with iodine and (t)BuNH2 resulted in crystallization of the Pu(III) complex
      [PuI2(thf)4(py)][I3] (4). Dissolution of a Pu(IV) carbonate with a HCl/Et2O
      solution in thf gave the mixed valent (III/IV) complex salt
      [PuCl2(thf)5][PuCl5(thf)] (5) as the only tractable product. Oxidation of
      Pu[N(SiMe3)2]3 with TeCl4 afforded the Pu(IV) complex Pu[N(SiMe3)2]3Cl (6), which
      may prove to be a useful entry route for investigation of organometallic/non
      aqueous tetravalent plutonium chemistry.

PMID- 18714990
TI  - Trinuclear {M1}CN{M2}2 complexes (M1 = Cr(III), Fe(III), Co(III); M2 = Cu(II),
      Ni(II), Mn(II)). Are single molecule magnets predictable?
AB  - The reaction of the hexacyanometalates K3[M(1)(CN)6] (M(1) = Cr(III), Fe(III),
      Co(III)) with the bispidine complexes [M(2)(L(1))(X)](n+) and [M(2)(L(2))(X)](n+)
      (M(2) = Mn(II), Ni(II), Cu(II); L(1) = 3-methyl-9-oxo-2,4-di-(2-pyridyl)-7-(2
      pyridylmethyl)-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarboxylic acid dimethyl
      ester; L(2) = 3-methyl-9-oxo-7-(2-pyridylmethyl)-2,4-di-(2-quinolyl)-3,7
      diazabicyclo[3.3.1]nonane-1,5-dicarboxylic acid dimethyl ester; X = anion or
      solvent) in water-methanol mixtures affords trinuclear complexes with cis- or
      trans-arrangement of the bispidine-capped divalent metal centers around the
      hexacyanometalate. X-ray structural analyses of five members of this family of
      complexes (cis-Fe[CuL(2)]2, trans-Fe[CuL(1)]2, cis-Co[CuL(2)]2, trans
      Cr[MnL(1)]2, trans-Fe[MnL(1)]2) and the magnetic data of the entire series are
      reported. The magnetic data of the cyanide bridged, ferromagnetically coupled cis
      and trans-Fe[ML]2 compounds (M = Ni(II), Cu(II)) with S = 3/2 (Cu(II)) and S =
      5/2 (Ni(II)) ground states are analyzed with an extended Heisenberg Hamiltonian
      which accounts for anisotropy and zero-field splitting, and the data of the
      Cu(II) systems, for which structures are available, are thoroughly analyzed in
      terms of an orbital-dependent Heisenberg Hamiltonian, in which both spin-orbit
      coupling and low-symmetry ligand fields are taken into account. It is shown that
      the absence of single-molecule magnetic behavior in all spin clusters reported
      here is due to a large angular distortion of the [Fe(CN)6](3-) center and the
      concomitant quenching of orbital angular momentum of the Fe(III) ((2)T2g) ground
      state.

PMID- 18714991
TI  - Two-vial, LC-MS identification of ephedrine receptors from a solution-phase
      dynamic combinatorial library of over 9000 components.
AB  - Reports on dynamic combinatorial chemistry have almost exclusively involved small
      libraries of 10-100 compounds. We now show how more than 9000 compounds can be
      screened in a single LC-MS analysis to reveal a series of new receptors that bind
      ephedrine in water. These results demonstrate the feasibility of screening DCLs
      that are substantially larger than the solution-phase libraries reported thus
      far.

PMID- 18714992
TI  - cis-Delta(2,3)-double bond of phoslactomycins is generated by a post-PKS
      tailoring enzyme.
AB  - The antifungal phoslactomycins (PLM A-F), produced by Streptomyces sp. HK803, are
      structurally unusual in that three of their four double bonds are in the cis form
      (Delta12,13, Delta14,15, Delta2,3). The PLM polyketide synthase (PKS) has the
      predicted dehydratase catalytic domain in modules 1, 2, and 5 required for
      establishing two of these cis double bonds (Delta12,13, Delta14,15), as well as
      the only trans Delta6,7 double bond. By contrast, the formation of the cis
      Delta2,3 in the unsaturated lactone moiety of PLMs has presented an enigma
      because the predicted dehydratase domain in module 7 is absent. Herein, we have
      demonstrated that the plmT2 gene product, with no homology to PKS dehydratase
      domains, is required for efficient formation of the cis Delta2,3 alkene. A series
      of new PLM products in which the C3 hydroxyl group is retained are made in plmT2
      deletion mutants. In all of these cases, however, the hydroxyl group is
      esterified with malonic acid. These malonylated PLM products are converted to the
      corresponding cis Delta2,3 PLM products and acetic acid by a facile base
      catalyzed decarboxylative elimination reaction. Complete or partial restoration
      of natural PLM production in a plmT2 deletion mutant can be accomplished by
      plasmid based expression of plmT2 or fos ORF4 (a homologous gene from the
      fostriecin biosynthetic gene cluster), respectively. The data indicate that
      dehydratase-independent pathways also function in establishment of unsaturated 6
      membered lactone moieties in other PKS pathways and provide the first
      biosynthetic insights into the possible routes by which unusual malonylated
      polyketide products are generated.

PMID- 18714993
TI  - Transitioning enantioselective indicator displacement assays for alpha-amino
      acids to protocols amenable to high-throughput screening.
AB  - Enantioselective indicator displacement assays (eIDAs) for alpha-amino acids were
      conducted in a 96-well plate format to demonstrate the viability of the technique
      for the high-throughput screening (HTS) of enantiomeric excess (ee) values.
      Chiral receptors [Cu(II)(1)](2+) and [Cu(II)(2)](2+) with the indicator chrome
      azurol S were implemented for the eIDAs. Enantiomeric excess calibration curves
      were made using both receptors and then used to analyze true test samples. These
      results were compared to those previously obtained with a conventional UV-vis
      spectrophotometer, and they showed little to no loss of accuracy, while the speed
      of analysis was increased. A sample of valine of unknown ee was synthesized
      through an asymmetric reaction to produce a realistic reaction sample, which was
      analyzed using receptor [Cu(II)(1)](2+). The experimentally determined ee using
      our eIDA was compared to that obtained by chiral HPLC and (1)H NMR chiral shift
      reagent analysis. This gave errors of 4.7% and 12.0%, respectively. In addition
      to the use of ee calibration curves, an artificial neural network (ANN) was used
      to determine the % L-amino acid of the test samples and of the sample of valine
      of unknown ee from the asymmetric reaction. This method obtained errors of 5.9%
      and 2.2% compared to chiral HPLC and (1)H NMR chiral shift reagent analysis,
      respectively. The technique using calibration curves for the determination of ee
      on a 96-well plate allows one to determine 96 ee values in under a minute,
      enabling its use for HTS of asymmetric reactions with acceptable accuracy.

PMID- 18714994
TI  - Diarylstannylene activation of hydrogen or ammonia with arene elimination.
AB  - Treatment of the stannylenes SnAr'2 (Ar' = C6H3-2,6(C6H3-2,6-Pri2)2), SnAr2# (Ar#
      = C6H3-2,6-(C6H2-2,4,6-Me3)2, or Sn{N(SiMe3)2}2 with H2, D2, or NH3 under
      identical, mild (1 atm, 65 degrees C) conditions showed that SnAr2' reacted
      readily to afford the products {Ar'Sn(mu-H)}2, {Ar'Sn(mu-D)}2, or {Ar'Sn(mu
      NH2)}2 with elimination of Ar'H or Ar'D. The less crowded stannylenes SnAr2# and
      Sn{N(SiMe3)2}2 were recovered unreacted. The differences in reactivity were
      accounted for in terms of the n-p energy separations which is lowest in the case
      of AnAr2'. The low energy separation in SnAr' is consistent with enhanced singlet
      diradical character of the ground state which increases its reactivity.

PMID- 18714995
TI  - An efficient low-temperature route to polycyclic isoquinoline salt synthesis via
      C-H activation with [Cp*MCl2]2 (M = Rh, Ir).
AB  - Bi-, tri-, and tetracyclic isoquinoline salts were readily synthesized in
      excellent yields at room temperature from readily available starting materials
      after three reaction steps. Aromatic C-H activation was first promoted by sodium
      acetate with [Cp*MCl2]2 (M = Rh, Ir) at room temperature to form cyclometalated
      compounds. Dimethylacetylenedicarboxylate was then found to insert into the metal
      carbon bonds of the cyclometalated compounds. Finally, the insertion compounds
      underwent oxidative coupling to form the desired isoquinoline salts and
      regenerate [Cp*MCl2]2. All of the intermediate compounds following C-H
      activation, alkyne insertion, and oxidative coupling were fully characterized,
      including the determination of X-ray structures in several cases, and the results
      shed light on the overall mechanism. Moreover, it was possible to synthesize the
      isoquinoline salts from readily available starting materials using one-pot
      procedures; thus, this work provides a novel, efficient method for metal-mediated
      synthesis of heterocycles.

PMID- 18714996
TI  - Using enantioselective indicator displacement assays to determine the
      enantiomeric excess of alpha-amino acids.
AB  - Enantioselective indicator displacement assays (eIDAs) were used for the
      determination of enantiomeric excess (ee) of alpha-amino acids as an alternative
      to the labor-intensive technique of chromatography. In this study, eIDAs were
      implemented by the use of two chiral receptors [(Cu(II)(1)](2+), [Cu(II)(2)](2+))
      in conjunction with the indicator chrome azurol S. The two receptors were able to
      enantioselectively discriminate 13 of the 17 analyzed alpha-amino acids.
      Enantiomeric excess calibration curves were made using both receptors and then
      used to analyze true test samples to check the system's ability to determine ee
      accurately. The proposed method uses a conventional UV-vis spectrophotometer to
      monitor the colorimetric signal, which allows for a potential high-throughput
      screening (HTS) method for determining ee. The techniques created consistently
      produced results accurate enough for rapid preliminary determination of ee.

PMID- 18714997
TI  - Alkali metal reductions of organic molecules: why mediated electron transfer from
      lithium is faster than direct reduction.
AB  - Lithium metal reductions are widely employed in organic synthesis, where it is
      common to employ a "mediator" to speed up the electron transfer kinetics. We
      present experimental data for the electrode kinetics of the reduction of the most
      common mediator, 4,4'-di-tert-butyl-1,1'-biphenyl (DBB) in tetrahydrofuran (THF)
      over a range of temperatures. Using corresponding data for the oxidation of
      lithium we present quantitative estimates of the kinetic advantage for the use of
      DBB as a mediator in lithium reductions, over, in particular, direct reduction
      using lithium metal.

PMID- 18714998
TI  - Successful dispersion polymerization in supercritical CO2 using polyvinylalkylate
      hydrocarbon surfactants synthesized and anchored via RAFT.
AB  - New CO2-philic hydrocarbon molecules were synthesized by reversible addition
      fragmentation chain-transfer polymerization. These poly(vinyl alkylates) show the
      highest solubility in supercritical CO2 of any hydrocarbon reported to date. By
      utilizing the anchoring ability of the thiocarbonylthio end group, the dispersion
      polymerization of N-vinyl pyrrolidone was successfully achieved in scCO2 leading
      to high yields of well-defined spherical polymer particles.

PMID- 18714999
TI  - A photolabile ligand for light-activated release of caged copper.
AB  - A photosensitive caged copper complex has been prepared from a tetradentate
      ligand (H2cage) composed of two pyridyl-amide arms connected by a photoreactive
      nitrophenyl group. H2cage binds Cu2+ in aqueous solution with a stability
      constant (log beta) of 10.8, which corresponds to a KD of 16 pM at pH 7.4. The
      neutral Cu2+ complex, [Cu(OH2)(cage)], crystallizes as a distorted trigonal
      bipyramid coordinated by two amide and two pyridyl N atoms, with a water molecule
      bound in the trigonal plane. Photolysis with 350 nm UV light cleaves the ligand
      backbone to release photoproducts with significantly diminished affinity for
      Cu2+, thereby uncaging the metal ion. When coordinated as the caged complex,
      copper has diminished reactivity to produce hydroxyl radicals from Fenton-like
      reaction mixtures containing hydrogen peroxide and ascorbic acid. Postphotolysis,
      uncaged copper promotes hydroxyl radical formation under the same conditions. The
      strategy of caging copper is promising for applications where light could be used
      to trigger release of copper as a pro-oxidant to increase oxidative stress or as
      a tool to release copper intracellularly to study mechanisms of copper
      trafficking.

PMID- 18715000
TI  - 1/infinity [ZrPSe6-]: a soluble photoluminescent inorganic polymer and strong
      second harmonic generation response of its alkali salts.
AB  - Zirconium selenophosphate compounds with a unique polar structure show strong
      second harmonic generation and they dissolve in polar solvent to produce
      photoluminescent solutions.

PMID- 18715001
TI  - Palladium-catalyzed Hiyama cross-couplings of aryl arenesulfonates with
      arylsilanes.
AB  - Palladium-catalyzed efficient Hiyama cross-coupling reaction of aryl
      arenesulfonate with arylsilane is described. The desired carbon-carbon bond
      formation proceeds under mild conditions with good functional group tolerance.

PMID- 18715002
TI  - Time-resolved dimerization of a PAS-LOV protein measured with photocoupled small
      angle X-ray scattering.
AB  - Time-resolved small-angle X-ray scattering (SAXS) has been used to probe
      photoexcitation of the blue-light signal transduction protein Vivid (VVD). Laser
      excitation of sample in a continuous flow cell enables time-resolved measurement
      of the initial response of VVD to illumination. Good signal-to-noise is achieved
      without relying on multiple exposures of the same sample or limiting exposure
      times to prevent radiation damage. The SAXS data demonstrate that VVD dimerizes
      within tens of milliseconds of light-state activation. Time-resolved SAXS in a
      flow cell format is a general method for connecting chemical changes in
      photoreceptors to conformationally driven output signals.

PMID- 18715004
TI  - Intermolecular, catalytic asymmetric hydroamination of bicyclic alkenes and
      dienes in high yield and enantioselectivity.
AB  - A set of catalytic, intermolecular hydroaminations of strained bicyclic olefins
      and dienes are reported that occur in both high yield and high
      enantioselectivity. These reactions occur with a catalyst generated from
      [Ir(cyclooctene)Cl]2, sterically hindered and electron-rich derivatives of the
      Segphos and BIPHEP family of ligands, and a soluble base. This system catalyzes
      the addition of various anilines to norbornene, norbornadiene, and other bicyclic
      olefins. The products from addition of p-anisidine can be transformed to BOC
      protected norbornylamine and to substituted cyclopentanes in nearly enantiopure
      form. Mechanistic studies show that addition of aniline-d2 occurs in a syn
      fashion and suggest that the catalytic cycle comprises oxidative addition of
      aniline to form a bis-anilide hydride complex, followed by migratory insertion of
      olefin and reductive elimination of product in a series of steps involving
      iridium complexes containing ancillary bisphosphine and arylamide ligands.

PMID- 18715003
TI  - Thermodynamic and structural basis of phosphorylation-induced disorder-to-order
      transition in the regulatory light chain of smooth muscle myosin.
AB  - We have performed molecular dynamics simulations of the phosphorylation domain
      (PD) of the regulatory light chain (RLC) of smooth muscle myosin, to gain insight
      into the thermodynamic principles governing the phosphorylation-induced disorder
      to-order transition. Simulations were performed in explicit water under near
      physiological conditions, starting with an ideal alpha-helix. In the absence of
      phosphorylation, the helical periodicity of the peptide was disrupted at residues
      T9-K11, while phosphorylation significantly favored the helical periodicity, in
      agreement with experimental data. Using the MM/PBSA approach, we calculated a
      relative free energy of -7.1 kcal/mol for the disorder-to-order transition. A
      large enthalpic decrease was compensated by a large loss of conformational
      entropy, despite the small helical increase (no more than three residues) upon
      phosphorylation. Phosphorylation decreased the conformational dynamics of K and R
      side chains, especially R16, which forms a salt bridge with pS19. Mutation of R16
      to A or E prevented this phosphorylation-dependent ordering. We propose that
      phosphorylation balances the enthalpy-entropy compensation of the disorder-to
      order transition of RLC via short and long-range electrostatic interactions with
      positively charged residues of the phosphorylation domain. We suggest that this
      balance is necessary to induce a disorder-to-order conformational change through
      a subtle energy switching.

PMID- 18715005
TI  - On the effect of low-energy electron induced DNA strand break in aqueous
      solution: a theoretical study indicating guanine as a weak link in DNA.
AB  - In this theoretical study we have investigated the effect of low-energy electrons
      attached onto a 3'-guanine monophosphate, 3'-GMP, in the gas phase and in aqueous
      solution. DFT calculations with B3LYP/DZP++ were performed to study the C3'-O3'
      bond break of a 3'-GMP radical anion. Our results show that low-energy electrons,
      if attached to a 3'-GMP with a neutrally charged phosphate group, can easily
      induce a C3'-3' bond break in both the gas phase and aqueous solution. The
      activation energy was found here to be 10.3 kcal/mol in the gas phase and, even
      lower, 5.3 kcal/mol in aqueous solution. In comparison with calculated activation
      energies for other nucleotides the 3'-GMP has the lowest energy barrier in
      aqueous solution.

PMID- 18715006
TI  - Polarization energies in oligoacene semiconductor crystals.
AB  - Characterization of the electronically polarized environment and the nuclear
      relaxation that accompanies charge carriers is fundamental to charge transport in
      crystalline, polycrystalline, and amorphous organic solids. To study the
      polarization effects of localized charged carriers, we use quantum/classical
      QM/MM approaches with charge redistribution and polarizable force field schemes
      and apply them to crystals of naphthalene through pentacene. We describe the
      results of a comprehensive investigation of the electronic polarization energies
      in molecular crystal structures of these oligoacenes and discuss as well the
      evolution of the nuclear relaxation energies calculated for model oligoacene
      systems.

PMID- 18715007
TI  - SnO2 quantum dots and quantum wires: controllable synthesis, self-assembled 2D
      architectures, and gas-sensing properties.
AB  - SnO2 quantum dots (QDs) and ultrathin nanowires (NWs) with diameters of
      approximately 0.5-2.5 and approximately 1.5-4.5 nm, respectively, were
      controllably synthesized in a simple solution system. They are supposed to be
      ideal models for studying the continuous evolution of the quantum-confinement
      effect in SnO2 1D --> 0D systems. The observed transition from strong to weak
      quantum confinement in SnO2 QDs and ultrathin NWs is interpreted through the use
      of the Brus effective-mass approximation and the Nosaka finite-depth well model.
      Photoluminescence properties that were coinfluenced by size effects, defects
      (oxygen vacancies), and surface capping are discussed in detail. With the SnO2
      QDs as building blocks, various 2D porous structures with ordered hexagonal,
      distorted hexagonal, and square patterns were prepared on silicon-wafer surfaces
      and exhibited optical features of 2D photonic crystals and enhanced gas
      sensitivity.

PMID- 18715008
TI  - Carbon dioxide activation with sterically pressured mid- and high-valent uranium
      complexes.
AB  - Sterically pressured mid- to high-valent uranium complexes with an aryloxide
      substituted triazacyclononane ligand scaffold, [(((R)ArO)3tacn)(3-)], were
      studied for carbon dioxide activation and transformation chemistry. The high
      valent uranium(V) imido species [(((R)ArO)3tacn)U(NR)] (R = (t)Bu, R' = 2,4,6
      trimethylphenyl (2-(t)Bu); R = Ad, R' = 2,4,6-trimethylphenyl (2-Ad); R = (t)Bu,
      R' = phenyl (3-(t)Bu)) were synthesized and spectroscopically characterized. X
      ray crystallography of the tert-butyl mesityl imido derivative, 2-(t)Bu , reveals
      coordination of a bent imido fragment with a relatively long U-N bond distance of
      2.05 A. The mesityl imido complexes reacted with carbon dioxide, readily
      extruding free isocyanate to produce uranium(V) terminal oxo species,
      [(((R)ArO)3tacn)U(O)] (R = (t)Bu (4-(t)Bu), Ad (4-Ad)), presumably through
      multiple bond metathesis via a uranium(V) carbimate intermediate. Using the
      smaller phenyl imido fragment in 3-(t) Bu slowed isocyanate loss, allowing the
      uranium(V) carbimate intermediate to undergo a second metathesis reaction,
      ultimately producing the diphenyl ureate derivative, [(((tBu)ArO)3tacn)U(NPh2)CO]
      (5-(t)Bu). Single crystal X-ray diffraction studies were carried out on both
      uranium(V) terminal oxo complexes and revealed short U-O bonds (1.85 A)
      indicative of a formal UO triple bond. The electronic structure of the oxo U(V)
      complexes was investigated by electronic absorption and EPR spectroscopies as
      well as SQUID magnetization and DFT studies, which indicated that their
      electronic properties are highly unusual. To obtain insight into the reactivity
      of CO2 with U-N bonds, the reaction of the uranium(IV) amide species,
      [(((R)ArO)3tacn)U(NHMes)] (R = (t)Bu (6-(t)Bu), Ad (6-Ad) with carbon dioxide was
      investigated. These reactions produced the uranium(IV) carbamate complexes,
      [(((R)ArO)3tacn)U(CO2NHMes)] (R = (t)Bu (7-(t)Bu), Ad (7-Ad)), resulting from
      insertion of carbon dioxide into U-N(amide) bonds. The molecular structures of
      the synthesized uranium carbamate complexes highlight the different reactivities
      due to the steric pressure introduced by the alkyl derivatized tris(aryloxide)
      triazacyclononane ligand. The sterically open tert-butyl derivative creates a
      monodentate eta(1)-O bound carbamate species, while the sterically more bulky
      adamantyl-substituted compound forces a bidentate kappa(2)-O,O coordination mode
      of the carbamate ligand.

PMID- 18715009
TI  - Catalytic enantioselective Reformatsky reaction with ortho-substituted
      diarylketones.
AB  - The catalytic enantioselective Reformatsky reaction with ortho-substituted
      diarylketones with good enantioselectivities and moderate to good yields is
      reported. A readily available BINOL derivative is used as a chiral catalyst, and
      the reactions are performed with ethyl iodoacetate as a nucleophile and Me2Zn as
      the zinc source. The presence of air was found to be crucial to achieve an
      effective C-C bond formation pointing to a radical mechanism.

PMID- 18715011
TI  - Stereoselective iterative one-pot synthesis of N-glycolylneuraminic acid
      containing oligosaccharides.
AB  - The use of an N-acyloxazolidinone-protected S-adamantanyl thiosialoside allows
      the highly stereoselective, one-pot multicomponent synthesis of alpha-sialoside
      based oligosaccharides.

PMID- 18715012
TI  - [(CyPF-(t)Bu)PdCl2]: an air-stable, one-component, highly efficient catalyst for
      amination of heteroaryl and aryl halides.
AB  - An air- and moisture-stable palladium catalyst, [(CyPF-(t)Bu)PdCl2] (1), for
      coupling of heteroaryl chlorides, bromides, and iodides with a variety of primary
      amines is described. Most of these reactions occurred in high yield with 0.001
      0.05 mol % catalyst loading. The reactions tolerated a wide range of functional
      groups.

PMID- 18715013
TI  - Novel 2,4-methanoadamantane-benzazepine by domino photochemistry of N-(1
      adamantyl)phthalimide.
AB  - The photochemical reaction of N-(1-adamantyl)phthalimide (1) gives cleanly one
      product, the novel hexacyclic benzazepine derivative of 2,4-methanoadamantane 2.
      Its structure was characterized by spectroscopic methods and X-ray analysis and
      represent the first example of the 2-azahexacyclo[8.7.1.1 (1,4).0 (4,9).0
      (11,16).0 (12,18)]nonadeca-4,6,8-triene skeleton. The product is formed by a
      domino process of two consecutive excited-state intramolecular gamma-hydrogen
      transfer reactions. Base hydrolysis of the benzazepine 2 gives in high yield the
      keto derivative of the 1,2-substituted adamantane epsilon-amino acid 3.

PMID- 18715014
TI  - Palladium-catalyzed selenoacylation of allenes leading to the regioselective
      formation of functionalized allyl selenides.
AB  - Palladium-catalyzed regio- and stereoselective selenoacylation of allenes with
      selenol esters proceeded to produce functionalized allyl selenides with the acyl
      moiety at the inner carbon and the SePh group at the terminal carbon in high
      yields. A mechanism accounting for the observed regio- and stereoselectivities is
      proposed based on the results of DFT calculations.

PMID- 18715015
TI  - Isothiocyanate concentration in Kohlrabi (Brassica oleracea L. Var. gongylodes)
      plants as influenced by sulfur and nitrogen supply.
AB  - Glucosinolates (GSss) represent bioactive compounds of Brassica vegetables whose
      health-promoting effects merely stem from their breakdown products, particularly
      the isothiocyanates (ITCs), released after hydrolysis of GSs by myrosinase. GSs
      are occasionally discussed as transient S reservoirs, but little is known
      concerning the interactive effect of S and N supply on ITC concentrations.
      Therefore, kohlrabi plants were grown in a pot experiment with varied S (0.00,
      0.05, and 0.20 g pot (-1)) and N (1, 2, and 4 g pot (-1)) supplies. Plant growth
      exhibited a classical nutrient response curve with respect to both S and N. The
      ITC profile of kohlrabi tubers was dominated by methylthiobutyl ITC (11-1350
      micromol (g DM) (-1)), followed by sulforaphan (7-120 micromol (g DM) (-1)),
      phenylethyl ITC (5-34 micromol (g DM) (-1)), and allyl ITC (5-38 micromol (g DM)
      (-1)), resulting from the hydrolysis of glucoerucin, glucoraphanin,
      gluconasturtiin, and sinigrin, respectively. The ITC profile was in agreement
      with reported data, and concentrations of all ITCs were substantially reduced in
      response to increasing N and decreasing S supply. A growth-induced dilution
      effect could be ruled out in most cases, and the results do not support the
      hypothesis that GS acts as transient reservoir with respect to S.

PMID- 18715016
TI  - Solution NMR structure of the NlpC/P60 domain of lipoprotein Spr from Escherichia
      coli: structural evidence for a novel cysteine peptidase catalytic triad.
AB  - Escherichia coli Spr is a membrane-anchored cell wall hydrolase. The solution NMR
      structure of the C-terminal NlpC/P60 domain of E. coli Spr described here reveals
      that the protein adopts a papain-like alpha+beta fold and identifies a substrate
      binding cleft featuring several highly conserved residues. The active site
      features a novel Cys-His-His catalytic triad that appears to be a unique
      structural signature of this cysteine peptidase family. Moreover, the relative
      orientation of these catalytic residues is similar to that observed in the
      analogous Ser-His-His triad, a variant of the classic Ser-His-Asp charge relay
      system, suggesting the convergent evolution of a catalytic mechanism in quite
      distinct peptidase families.

PMID- 18715017
TI  - Multiplexed affinity-based protein complex purification.
AB  - Here we proved the principle of a multiplexed affinity-based protein complex
      purification (MAPcP) technique that targets simultaneous extraction of multiple
      protein complexes with superior purity. Microspheres of various sizes and coupled
      with different affinity probes extract several protein complexes concurrently and
      specifically. After the coextraction, flow-field flow fractionation (Fl-FFF)
      rapidly washes the microspheres as well as separates them based on their sizes to
      recover the clean individual complex for downstream analysis. Demonstration of
      the parallel extraction of two immuno-complexes from the yeast whole cell lysate
      showed that MAPcP can enhance the sample purity significantly compared to the
      traditional centrifugation and magnetic pull-down methods used for small scale
      protein purification. Simultaneous isolation of multiple protein complexes can
      facilitate the elucidation of the functional relationship among protein complexes
      and improve our understanding of the biological network.

PMID- 18715018
TI  - Optimized time alignment algorithm for LC-MS data: correlation optimized warping
      using component detection algorithm-selected mass chromatograms.
AB  - Correlation optimized warping (COW) based on the total ion current (TIC) is a
      widely used time alignment algorithm (COW-TIC). This approach works successfully
      on chromatograms containing few compounds and having a well-defined TIC. In this
      paper, we have combined COW with a component detection algorithm (CODA) to align
      LC-MS chromatograms containing thousands of biological compounds with overlapping
      chromatographic peaks, a situation where COW-TIC often fails. CODA is a variable
      selection procedure that selects mass chromatograms with low noise and low
      background (so-called "high-quality" mass chromatograms). High-quality mass
      chromatograms selected in each COW segment ensure that the same compounds (based
      on their mass and their retention time) are used in the two-dimensional benefit
      function of COW to obtain correct and optimal alignments (COW-CODA). The
      performance of the COW-CODA algorithm was evaluated on three types of complex
      data sets obtained from the LC-MS analysis of samples commonly used for biomarker
      discovery and compared to COW-TIC using a new global comparison method based on
      overlapping peak area: trypsin-digested serum obtained from cervical cancer
      patients, trypsin-digested serum from a single patient that was treated with
      varying preanalytical parameters (factorial design study), and urine from
      pregnant and nonpregnant women. While COW-CODA did result in minor misalignments
      in rare cases, it was clearly superior to the COW-TIC algorithm, especially when
      applied to highly variable chromatograms (factorial design, urine). The presented
      algorithm thus enables automatic time alignment and accurate peak matching of
      multiple LC-MS data sets obtained from complex body fluids that are often used
      for biomarker discovery.

PMID- 18715019
TI  - Solvent-free synthesis of Janus colloidal particles.
AB  - Taking advantage of the quick and efficient access of vapor to surfaces, a
      simple, solvent-free method is demonstrated to synthesize Janus colloidal
      particles in large quantity and with high efficiency. First, at the liquid-liquid
      interface of emulsified molten wax and water, untreated silica particles adsorb
      and are frozen in place when the wax solidifies. The exposed surfaces of the
      immobilized particles are modified chemically by exposure to silane vapor and, in
      principle, subsequent dissolution of the wax opens up the inner particle surface
      for further chemical modification. Applying this scheme, this paper describes the
      production of amphiphilic Janus particles (hydrophobic on one side, hydrophilic
      on the other) and dipolar Janus particles (positively charged on one side,
      negatively charged on the other). Janus geometry is confirmed by fluorescence
      microscopy and flow cytometry. Amphiphilic Janus particles are found to adsorb
      strongly to the water-oil interface, whereas dipolar particles assemble into
      chains in the aqueous phase.

PMID- 18715020
TI  - Water/supercritical CO2 microemulsions with mixed surfactant systems.
AB  - Phase behavior was investigated for water/supercritical CO 2 (W/scCO2)
      microemulsions stabilized with sodium bis(1H,1H,2H,2H-heptadecafluorodecyl)-2
      sulfosuccinate (8FS(EO) 2) mixed with various guest surfactants. Only for the
      mixtures with fluorocarbon-hydrocarbon hybrid anionic surfactants (FC6-HC n), the
      maximum water-to-surfactant molar ratio (W0(c)) was larger than that estimated
      from linear interpolation of the W0(c) values for pure 8FS(EO) 2 and pure guest
      surfactant. Fourier transform infrared (FT-IR) measurement for the microemulsion
      revealed that the mixing of 8FS(EO) 2 with FC6-HC n can prevent a phase
      transition from the microemulsion to the liquid crystal even in the presence of
      excess water. It was also found from the measurement of water/scCO 2 interfacial
      tension that the area occupied per surfactant molecule was markedly increased by
      the mixing with FC6-HC n. The loose molecular packing, probably due to a
      microsegregation of 8FS(EO) 2 and FC6-HC n, is consistent with the enhanced
      stability of the microemulsion upon surfactant mixing.

PMID- 18715021
TI  - Exploring the interfacial structure of protein adsorbates and the kinetics of
      protein adsorption: an in situ high-energy X-ray reflectivity study.
AB  - The high energy X-ray reflectivity technique has been applied to study the
      interfacial structure of protein adsorbates and protein adsorption kinetics in
      situ. For this purpose, the adsorption of lysozyme at the hydrophilic silica
      water interface has been chosen as a model system. The structure of adsorbed
      lysozyme layers was probed for various aqueous solution conditions. The effect of
      solution pH and lysozyme concentration on the interfacial structure was measured.
      Monolayer formation was observed for all cases except for the highest
      concentration. The adsorbed protein layers consist of adsorbed lysozyme molecules
      with side-on or end-on orientation. By means of time-dependent X-ray reflectivity
      scans, the time-evolution of adsorbed proteins was monitored as well. The results
      of this study demonstrate the capabilities of in situ X-ray reflectivity
      experiments on protein adsorbates. The great advantages of this method are the
      broad wave vector range available and the high time resolution.

PMID- 18715022
TI  - Functional gold nanoparticle-peptide complexes as cell-targeting agents.
AB  - In this paper, we report a novel approach using peptide CALNN and its derivative
      CALNNGGRRRRRRRR (CALNNR(8)) to functionalize gold nanoparticles for intracellular
      component targeting. The translocation is effected by the nanoparticle diameter
      and CALNNR(8) surface coverage. The intracellular distributions of the complexes
      are change from the cellular nucleus to the endoplasmic reticulum by increasing
      the density of CALNNR(8) at a constant nanoparticle diameter. Additionally,
      increasing the nanoparticle diameter at a constant density of CALNNR(8) leads to
      less cellular internalization. These translocations of the complexes cause unique
      colorimetric expressions of the cell structure. The cell viability is affected by
      the internalized gold nanoparticle-peptide complexes in terms of quantities of
      particles per cell. In addition, the intracellular distribution of the
      fluorescence quenching is investigated by a fluorescent confocal scanning laser
      microscopy, which also gives further evidence of intracellular distribution of
      the gold nanoparticle-peptide complexes.

PMID- 18715023
TI  - Fabrication of novel multihollow superparamagnetic magnetite/polystyrene
      nanocomposite microspheres via water-in-oil-in-water double emulsions.
AB  - We herein present a novel and simple synthetic strategy for fabricating
      multihollow superparamagnetic magnetite/polystyrene nanocomposite microspheres
      via water-in-oil-in-water double emulsions. Amphipathic magnetite nanoparticles
      surface-modified with oleic acid act as an oil-soluble emulsifier and sodium
      dodecyl sulfate acts as a water-soluble surfactant in the system. The final
      products were thoroughly characterized by X-ray powder diffraction, Fourier
      transform infrared spectroscopy, transmission electron microscopy, and field
      emission scanning electron microscopy, which showed the formation of multihollow
      magnetite/polystyrene nanocomposite microspheres. Preliminary results of magnetic
      properties of multihollow magnetite/polystyrene microspheres were reported. The
      effect of the content of amphipathic magnetite nanoparticles on the morphology of
      nanocomposite microspheres was studied. Furthermore, the mechanism of formation
      of multihollow magnetic nanocomposite microspheres was also discussed.

PMID- 18715024
TI  - Effect of mechanical stress on the kinetics of heterogeneous electron transfer.
AB  - The scanning electrochemical microscope (SECM) combined with a computerized
      tensile stage was employed to measure the kinetics of electron transfer (ET)
      reactions at stainless steel electrodes as a function of the applied mechanical
      stress. Reproducible current versus distance curves were obtained for different
      values of the tensile stress applied to a stainless steel (T-316) sample by using
      hexaammineruthenium as a redox mediator. The dependences of the extracted rate
      constant on substrate potential (i.e., Tafel plots, ln k versus E) were linear,
      in agreement with classical electrochemical theory. Possible origins of the
      stress effect on the ET rate and its implications for studies of stress corrosion
      cracking are discussed.

PMID- 18715025
TI  - Preparation of transparent conductive multilayered films using active
      pentafluorophenyl ester modified multiwalled carbon nanotubes.
AB  - A multilayered film was prepared by layer-by-layer (LBL) assembly of active ester
      modified multiwalled carbon nanotubes (MWCNTs) and poly(allylamine hydrochloride)
      (PAH). For this purpose, carboxylic groups on the surface of the oxidized MWCNTs
      were converted to the acyl chlorides by their reaction with thionyl chloride.
      Subsequent reaction of the acyl chlorides with pentafluorophenol formed the
      active esters. These active ester modified MWCNTs (MWCNTs-COOC(6)F(5)) were air
      stable and moisture resistant, but showed a high reactivity toward primary or
      secondary amines resulting in amide bonds. For the preparation of a multilayered
      film, the surface of a quartz slide was first activated and sacrificial double
      layers of PAH and poly(sodium 4-styrene sulfonate) (PSS) were deposited.
      Subsequently, LBL assembly of MWCNTs-COOC(6)F(5) and PAH was then conducted on
      these double layers [(PAH/PSS)2]. In the process of the assembly, a reaction
      occurred between the active ester on the surface of MWCNTs and the amine groups
      of polyallylamine yielding amide bonds, which resulted in a mechanically stable
      thin film. A free-standing film was obtained after dissolving the sacrificial
      layer [(PAH/PSS)2] in a concentrated aqueous NaOH solution. The surface
      resistance of the multilayered film with 20 bilayers decreased to around 10
      kOmega while remaining a reasonable transparency (70% at 500 nm).

PMID- 18715026
TI  - Cation exchange at the mineral-water interface: H3O+/K+ competition at the
      surface of nano-muscovite.
AB  - This article describes a (39)K nuclear magnetic resonance (NMR) spectroscopic
      study of K+ displacement at the muscovite/water interface as a function of
      aqueous phase pH. (39)K NMR spectra and T 2 relaxation data for nanocrystalline
      muscovite wet with a solid/solution weight ratio of 1 at pH 1, 3, and 5.5 show
      substantial liquid-like K+ only at pH 1. At pH 3 and 5.5, all K+ appears to be
      associated with muscovite as inner- or outer-sphere complexes, indicating that
      H(3)O+ does not displace basal surface K+ beyond the (39)K detection limit under
      these conditions. In our pH 1 mixture, only approximately 1/3 of the initial
      basal surface K+ population is located more than 3-4 A from the surface. (29)Si
      and (27)Al MAS NMR spectra and SEM images show no evidence of dissolution during
      the (39)K experiments, consistent with the liquid-like (39)K fraction originating
      from displaced basal surface K+. Assuming no muscovite dissolution or interlayer
      exchange, the K+/H(3)O+ ratio relevant to the solution/surface exchange
      equilibrium is controlled by the total amount of K+ on the surface and H(3)O+ in
      solution (K+(surf)/H(3)O+(aq)). These parameters, in turn, depend on the basal
      surface area, solution pH, and the solid/solution ratio. The results here are
      consistent with significant displacement of surface K+ only under conditions
      where the initial K+(surf)/H(3)O+(aq). ratio is less than approximately 1.
      Computational molecular models of the muscovite/water interface should account
      for both K+ and H(3)O+ in the near-surface region.

PMID- 18715027
TI  - Tuning of thermo-responsive self-assembly monolayers on gold for cell-type
      specific control of adhesion.
AB  - Self-assembled monolayers (SAMs) on gold containing a thermo-responsive poly( N
      isopropylacrylamide)-poly(ethylene glycol)-thiol copolymer were formed. These
      layers show considerable potential for inducing enzyme-free and gentle detachment
      of cultivated cells. In an effort to optimize detachment of cells, including
      strongly adhering ones, two approaches are presented. First, two thermo
      responsive copolymers with different poly(ethylene glycol) (PEG) contents of 15
      wt % ("P15") and 19 wt % ("P19") were grafted to Au surfaces. Second, mixed
      monolayers were formed containing P19 and various concentrations of thiol bearing
      PEG. X-ray photoelectron spectroscopy (XPS) on pure and mixed P19 containing
      layers confirmed the expected layer compositions. Contact angle measurements
      showed good functionality of all surfaces prepared. Upon a temperature decrease
      below the lower critical solution temperature (LCST), the duration until
      cultivated fibroblasts detached from pure P19 surfaces was half of the one
      determined on P15. Strongly adherent human osteosarcoma cells could not be
      detached from pure P19 layers. Through co-adsorption of P19 and thiol-bearing PEG
      of a molar composition of 1:6, layers were formed that allowed good spreading of
      osteosarcoma cells above LCST and their efficient detachment below LCST.

PMID- 18715028
TI  - A quantitative proteomic approach for identification of potential biomarkers in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. In this
      study, our objective was to identify differentially regulated proteins in HCC
      through a quantitative proteomic approach using iTRAQ. More than 600 proteins
      were quantitated of which 59 proteins were overexpressed and 92 proteins were
      underexpressed in HCC as compared to adjacent normal tissue. Several
      differentially expressed proteins were not implicated previously in HCC. A subset
      of these proteins (six each from upregulated and downregulated groups) was
      further validated using immunoblotting and immunohistochemical labeling. Some of
      the overexpressed proteins with no previous description in the context of HCC
      include fibroleukin, interferon induced 56 kDa protein, milk fat globule-EGF
      factor 8, and myeloid-associated differentiation marker. Interestingly, all the
      enzymes of urea metabolic pathway were dramatically downregulated.
      Immunohistochemical labeling confirmed differential expression of fibroleukin,
      myeloid associated differentiation marker and ornithine carbamoyl transferase in
      majority of HCC samples analyzed. Our results demonstrate quantitative proteomics
      as a robust discovery tool for the identification of differentially regulated
      proteins in cancers.

PMID- 18715029
TI  - Integrative proteomic and cytological analysis of the effects of extracellular
      Ca(2+) influx on Pinus bungeana pollen tube development.
AB  - Ca (2+) is an essential ion in the control of pollen germination and tube growth.
      However, the control of pollen tube development by Ca (2+) signaling and its
      interactions with cytoskeletal components, energy-providing pathways, and cell
      expansion machinery remain elusive. Here, we used nifedipine (Nif) to study Ca
      (2+) functions in differential protein expression and other cellular processes in
      Pinus bungeana pollen tube growth. Proteomics analysis indicated that 50 proteins
      showed differential expression with varying doses of Nif. Thirty-four of these
      were homologous to previously reported proteins and were classified into
      different functional categories closely related to tip-growth machinery. Blocking
      the L-type Ca (2+) channel with Nif in the pollen tube membrane induced several
      early alterations within a short time, including a reduction of extracellular Ca
      (2+) influx and a subsequently dramatic decrease in cytosolic free Ca (2+)
      concentration ([Ca (2+)] c), concomitant with ultrastructural abnormalities and
      changes in the abundance of proteins involved in energy production and signaling.
      Secondary alterations included actin filament depolymerization, disrupted
      patterns of endocytosis/exocytosis, and cell wall remodeling, along with changes
      in the proteins involved in these processes. These results suggested that
      extracellular Ca (2+) influx was necessary for the maintenance of the typical tip
      focused [Ca (2+)] c gradient in the P. bungeana pollen tube, and that reduced
      adenosine triphosphate production (ATP), depolymerization of the cytoskeleton,
      and abnormal endocytosis/exocytosis, together with enhanced rigidity of cell
      walls, were responsible for the growth arrest observed in pollen tubes treated
      with Nif.

PMID- 18715030
TI  - Development of a sialic acid-containing hydrogel of poly[N-(2-hydroxypropyl)
      methacrylamide]: characterization and implantation study.
AB  - This study describes the preparation and the characterization of poly[ N-(2
      hydroxypropyl methacrylamide)] hydrogel with bulk-modified saccharidic portion of
      ganglioside GM 3 (Neu5Ac-alpha2,3-Gal-beta1,4-Glc). The 3'-sialyllactose is a
      bioactive epitope recognized by many cell surface receptors on viruses, bacteria,
      and human cells such as growth factor receptors. Acrylated 3'-sialyllactose was
      synthesized and incorporated into the macromolecular network of hydrogels by free
      radical cross-linking copolymerization. Fluorescence techniques coupled to
      confocal laser scanning microscopy was employed to characterize the binding and
      accessibility of the sialyl group in the polymer network by using a monoclonal
      antibody against GM 3 and the lectin wheat germ agglutinin. The morphology of the
      network was examined by scanning electron microscopy and confocal microscopy to
      image the gel morphology. The water content of sialyllactosyl-HPMA hydrogel
      compared to unmodified gel was characterized by swelling measurements and
      thermogravimetry. A preliminary implantation study in rat brain was performed to
      examine the biofunctionality of the sialyllactosyl hydrogel using an experimental
      model of Parkinson's disease.

PMID- 18715031
TI  - Functionalization of magnetic nanowires by charged biopolymers.
AB  - We report on a facile method for the preparation of biocompatible and bioactive
      magnetic nanowires. The method consists of the direct deposition of
      polysaccharides by layer-by-layer (LbL) assembly onto a brush of metallic
      nanowires obtained by electrodeposition of the metal within the nanopores of an
      alumina template supported on a silicon wafer. Carboxymethylpullulan (CMP) and
      chitosan (CHI) multilayers were grown on brushes of Ni nanowires; subsequent
      grafting of an enzyme was performed by conjugating free amine side groups of
      chitosan with carboxylic groups of the enzyme. The nanowires are finally released
      by a gentle ultrasonic treatment. Transmission electron microscopy, electron
      energy-dispersive loss spectroscopy, and x-ray photoelectron spectroscopy
      indicate the formation of an homogeneous coating onto the nickel nanowires when
      one, two, or three CMP/CHI bilayers are deposited. This easy and efficient route
      to the biochemical functionalization of magnetic nanowires could find widespread
      use for the preparation of a broad range of nanowires with tailored surface
      properties.

PMID- 18715032
TI  - Manipulating DNA probe presentation via enzymatic cleavage of diluent strands.
AB  - We previously reported a system for the controlled redispersion of DNA-linked
      aggregates using secondary, competitive hybridization events and found that
      complete redispersion is contingent upon dilution of the active 20 base-long
      probe strands with 20 base-long nonhybridizing strands. Here, to reduce the
      steric interference of nonhybridizing or diluent strands on probe activity, we
      investigate the effect of shorter diluent strands on the hybridization activity
      of immobilized probes using the following two approaches: (1) simultaneously
      coupling shorter diluent strands and longer probe strands to microspheres and (2)
      simultaneously coupling diluent and probe strands of the same base length to
      microspheres and then clipping diluent strands with the restriction endonuclease
      AluI. Results indicate that one can reduce the duplex density down by 50-70% of
      its initial value, depending on the location of the recognition motif along the
      hybridization segment. In addition, tighter control over the number of probe
      target duplexes is achieved with the enzyme-based approach.

PMID- 18715033
TI  - Formation of brown lines in paper: characterization of cellulose degradation at
      the wet-dry interface.
AB  - Brown lines were generated at the wet-dry interface on Whatman paper No. 1 by
      suspending the sheet vertically in deionized water. Formic acid and acetic acid
      were quantified in three areas of the paper defined by the wet-dry boundary
      (above, below, and at the tideline) using capillary zone electrophoresis with
      indirect UV detection. Their concentration increased upon accelerated aging of
      the paper and was highest in the tideline. The hydroperoxides have been
      quantified using reverse phase high performance liquid chromatography with UV
      detection based on the determination of triphenylphosphine oxide produced from
      the reaction with triphenylphosphine, and their highest concentration was found
      in the tideline as well. For the first time, it was shown that various types of
      hydroperoxides were present, water-soluble and non-water-soluble, most probably
      in part hydroperoxide functionalized cellulose. After accelerated aging, a
      significant increase in hydroperoxide concentration was found in all the paper
      areas. The molar masses of cellulose determined using size-exclusion
      chromatography with multiangle light scattering detection showed that, upon
      aging, cellulose degraded significantly more in the tideline area than in the
      other areas of the paper. The area below the tideline was more degraded than the
      area above. A kinetic study of the degradation of cellulose allowed determining
      the constants for glycosidic bond breaking in each of the areas of the paper.

PMID- 18715034
TI  - Furan oligomers and beta-carbolines from terrestrial streptomycetes.
AB  - 2,5-Bis(hydroxymethyl)furan monoacetate (3) and 2,5-bis(hydroxymethyl)furan
      diacetate (4) were obtained as new natural products from an ethyl acetate extract
      of the terrestrial Streptomyces sp. isolate GW11/1695. Another Streptomyces
      isolate, GW21/1313, delivered a dimer (6) and a trimer (7) of
      (hydroxymethyl)furfural. The latter strain also produced 4-hydroxy-2-(5
      (hydroxymethyl)furan-2-ylmethylene)-5-methylfuran-3-one (5), perlolyrin (8), and
      two new beta-carboline derivatives, 9 and 10. 2,5-Bis(hydroxymethyl)furan
      diacetate (4) exhibited weak cytotoxic activity against brine shrimp larvae.

PMID- 18715035
TI  - Synechoxanthin, an aromatic C40 xanthophyll that is a major carotenoid in the
      cyanobacterium Synechococcus sp. PCC 7002.
AB  - A major aromatic, dicarboxylate carotenoid (>15% of total) was isolated from the
      euryhaline cyanobacterium Synechococcus sp. PCC 7002. This compound, which was
      given the common name synechoxanthin (1), has been assigned the structure (all-E)
      chi,chi-caroten-18,18'-dioic acid by a combination of spectroscopic (UV-vis, FT
      IR, (1)H and (13)C NMR, LC-MS) and chemical methods. This discovery conclusively
      establishes that some cyanobacteria are capable of synthesizing aromatic
      carotenoids.

PMID- 18715036
TI  - Viridamides A and B, lipodepsipeptides with antiprotozoal activity from the
      marine cyanobacterium Oscillatoria nigro-viridis.
AB  - Parallel chemical and phylogenetic investigation of a marine cyanobacterium from
      Panama led to the isolation of two new PKS-NRPS-derived compounds, viridamides A
      and B. Their structures were determined by NMR and mass spectroscopic methods,
      and the absolute configurations assigned by Marfey's method and chiral HPLC
      analysis. In addition to six standard, N-methylated amino and hydroxy acids,
      these metabolites contained the structurally novel 5-methoxydec-9-ynoic acid
      moiety and an unusual proline methyl ester terminus. Morphologically, this
      cyanobacterium was identified as Oscillatoria nigro-viridis, and its 16S rDNA
      sequence is reported here for the first time. Phylogenetic analysis of these
      sequence data has identified O. nigro-viridis strain OSC3L to be closely related
      to two other marine cyanobacterial genera, Trichodesmium and Blennothrix.
      Viridamide A showed antitrypanosomal activity with an IC50 of 1.1 microM and
      antileishmanial activity with an IC50 of 1.5 microM.

PMID- 18715038
TI  - The unexpected isolation of CTP-431, a novel thiopyrone from the sponge
      Cacospongia mycofijiensis.
AB  - A reinvestigation of a Fijian collection of Cacospongia mycofijiensis has yielded
      the known mycothiazole and a novel heterocyclic, CTP-431 (1). Its structure
      including absolute configuration as 8R,9R,10S,13S was established using NMR data,
      calculated DFT (13)C chemical shifts and results from X-ray crystallography. It
      is possible that the tricyclic skeleton of CTP-431 (1) is biosynthetically
      related to the macrolide latrunculin A, however the thiopyrone moiety of 1 has no
      previous precedent in natural products chemistry.

PMID- 18715039
TI  - A stereoselective approach to the azaspiro[5.5]undecane ring system using a
      conjugate addition/dipolar cycloaddition cascade: application to the total
      synthesis of (+/-)-2,7,8-epi-perhydrohistrionicotoxin.
AB  - An efficient stereocontrolled route to the spirocyclic perhydrohistrionicotoxin
      derivative (+/-)-2,7,8-epi-PHTx (4) is described. The reaction of 2-butyl-3
      (methoxymethoxy)cyclohexanone oxime with 2,3-bis(phenylsulfonyl)-1,3-butadiene
      gives rise to a 7-oxa-1-azanorbornane cycloadduct in high yield. The formation of
      the bicyclic isoxazolidine arises from conjugate addition of the oxime onto the
      diene to give a transient nitrone which then undergoes an intramolecular dipolar
      cycloaddition. Treatment of the cycloadduct with 5% Na/Hg results in reductive
      nitrogen-oxygen bond cleavage to furnish an azaspiro[5.5]undecane. Elaboration to
      the dihydropyridin-4(1H)-one 24 was followed by stereoselective conjugate
      addition using n-pentyl cuprate to give azaspirocycle 25. The stereochemistry of
      the product was deduced from an X-ray crystal structure of the corresponding N
      tosylhydrazone derivative. The dominant factor controlling the stereochemistry of
      the conjugate addition is the A(1,3)-strain present in the planar vinylogous
      amide. A stereoelectronically preferred axial attack by the organocuprate at the
      beta-position leads to the observed diastereoselectivity. Azaspirocycle 25 was
      transformed into 2,7,8-epi-PHTx (4) in five additional steps. Utilizing this
      tandem conjugate addition/dipolar cycloaddition cascade, we have also
      successfully synthesized azaspiro[5.5]undecane 36, which had previously been
      converted into (+/-)-perhydrohistrionicotoxin (2), thereby completing a formal
      total synthesis of this alkaloid.

PMID- 18715040
TI  - Efficient ytterbium triflate catalyzed microwave-assisted synthesis of 3
      acylacrylic acid building blocks.
AB  - The derivatives of 4-(hetero)aryl-4-oxobut-2-enoic acid are useful as building
      blocks in the synthesis of biologically active compounds. An efficient general
      protocol for the synthesis of these building blocks was developed. This method
      combines microwave assistance and ytterbium triflate catalyst and allows the fast
      preparation of the target acids starting from different (hetero)aromatic ketones
      and glyoxylic acid monohydrate giving pure products in 52-75% isolated yields.

PMID- 18715041
TI  - Magneto-optical-trap-based, high brightness ion source for use as a nanoscale
      probe.
AB  - We report on the demonstration of a low emittance, high brightness ion source
      based on magneto-optically trapped neutral atoms. Our source has ion optical
      properties comparable to or better than those of the commonly used liquid metal
      ion source. In addition, it has several advantages that offer new possibilities,
      including high resolution ion microscopy with ion species tailored for specific
      applications, contamination-free ion milling, and nanoscale implantation of a
      variety of elements, either in large quantities, or one at a time,
      deterministically. Using laser-cooled Cr atoms, we create an ion beam with a
      normalized rms (root-mean-square) emittance of 6.0 x 10 (-7) mm mrad M e V and
      approximately 0.25 pA of current, yielding a brightness as high as 2.25 A cm (-2)
      sr (-1) eV (-1). These values of emittance and brightness show that, with
      suitable ion optics, an ion beam with a useful amount of current can be produced
      and focused to spot sizes of less than 1 nm.

PMID- 18715042
TI  - Growth of manganese oxide nanoflowers on vertically-aligned carbon nanotube
      arrays for high-rate electrochemical capacitive energy storage.
AB  - Manganese oxide nanoflower/carbon nanotube array (CNTA) composite electrodes with
      hierarchical porous structure, large surface area, and superior conductivity was
      controllable prepared by combining electrodeposition technique and a vertically
      aligned CNTA framework. This binder-free manganese oxide/CNTA electrode presents
      excellent rate capability (50.8% capacity retention at 77 A/g), high capacitance
      (199 F/g and 305 F/cm (3)), and long cycle life (3% capacity loss after 20,000
      charge/discharge cycles), with strong promise for high-rate electrochemical
      capacitive energy storage applications.

PMID- 18715043
TI  - TiO2 nanowire bundle microelectrode based impedance immunosensor for rapid and
      sensitive detection of Listeria monocytogenes.
AB  - A novel TiO 2 nanowire bundle microelectrode based immunosensor was demonstrated
      as a more sensitive, specific, and rapid technology for detection of Listeria
      monocytogenes. TiO 2 nanowire bundle was prepared through a hydrothermal reaction
      of alkali with TiO 2 powder and connected to gold microelectrodes with mask
      welding. Monoclonal antibodies were immobilized on the surface of a TiO 2
      nanowire bundle to specifically capture L. monocytogenes. Impedance change caused
      by the nanowire-antibody-bacteria complex was measured and correlated to
      bacterial number. This nanowire bundle based immunosensor could detect as low as
      10 (2) cfu/ml of L. monocytogenes in 1 h without significant interference from
      other foodborne pathogens.

PMID- 18715044
TI  - Phase-separation transition in liquid mixtures near curved charged objects.
AB  - We study the thermodynamic behavior of nonpolar liquid mixtures in the vicinity
      of curved charged objects, such as electrodes or charged colloids. There is a
      critical value of charge (or potential), above which a phase-separation
      transition occurs, and the interface between high- and low-dielectric constant
      components becomes sharp. Analytical and numerical composition profiles are
      given, and the equilibrium front location as a function of charge or voltage is
      found. We further employ a simple Cahn-Hilliard type equation to study the
      dynamics of phase separation in spatially nonuniform electric fields. We find an
      exponential temporal relaxation of the demixing front location. We give the
      dependence of the steady-state location and characteristic time on the charge,
      mixture composition and ambient temperature.

PMID- 18715045
TI  - Reappraisal of cis effect in 1,2-dihaloethenes: an improved virtual orbital
      multireference approach.
AB  - Computed relative stabilities for isomers of 1,2-difluoroethene and 1,2
      dichloroethene isomers are compared with predictions based on chemical hardness
      (eta) and electrophilicity (omega) using the principles of maximum hardness and
      minimum electrophilicity. The chemical hardness and electrophilicity deduced
      either from improved virtual orbital (IVO) energies or from correlated treatments
      correctly predict that cis 1,2-difluoroethene and 1,2-dichloroethene are
      energetically more stable than the corresponding trans isomers, and the ground
      state energies from multireference perturbation theory with IVO orbitals agree
      with these predictions. However, when the same quantities are computed using
      Hartree-Fock orbitals, serious inconsistencies between the two approaches emerge
      in predicting the stability of the isomers of the 1,2-dihaloethenes. The present
      study clearly demonstrates that the IVO energies are appropriate for the
      computation of hardness related parameters, notably the chemical hardness and
      electrophilicity. Moreover, the IVO methods also provide smooth potential energy
      curves for the cis-trans isomerization of the two 1,2-dihaloethenes.

PMID- 18715046
TI  - A gradient-directed Monte Carlo approach to molecular design.
AB  - The recently developed linear combination of atomic potentials (LCAP) approach
      [M. Wang et al., J. Am. Chem. Soc. 128, 3228 (2006)] allows continuous
      optimization in a discrete chemical space, and thus is useful in the design of
      molecules for targeted properties. To address further challenges arising from the
      rugged, continuous property surfaces in the LCAP approach, we develop a gradient
      directed Monte Carlo (GDMC) strategy as an augmentation to the original LCAP
      optimization method. The GDMC method retains the power of exploring molecular
      space by utilizing local gradient information computed from the LCAP approach to
      jump between discrete molecular structures. It also allows random MC moves to
      overcome barriers between local optima on property surfaces. The combined GDMC
      LCAP approach is demonstrated here for optimizing nonlinear optical properties in
      a class of donor-acceptor substituted benzene and porphyrin frameworks.
      Specifically, one molecule with four nitrogen atoms in the porphyrin ring was
      found to have a larger first hyperpolarizability than structures with the
      conventional porphyrin motif.

PMID- 18715047
TI  - Monte Carlo configuration interaction predictions for the electronic spectra of
      Ne, CH2, C2, N2, and H2O compared to full configuration interaction calculations.
AB  - Singlet and triplet electronic excitation energies have been calculated for Ne,
      CH(2), C(2), N(2), and H(2)O using the Monte Carlo configuration interaction (CI)
      method. We find that excitation energies can be predicted to within a few tens of
      meV of full CI (FCI) results using expansions consisting of only a few thousand
      configuration state functions as compared to the O(10(8)) configurations
      occurring in the corresponding FCI expansions. The method provides a consistently
      accurate and balanced description of electronic excitations with accuracy for
      small molecular systems comparable to the equation-of-motion coupled cluster
      method with full triples.

PMID- 18715048
TI  - The spin-flip extended single excitation configuration interaction method.
AB  - An extension of the spin-flip single excitation configuration interaction (SF
      CIS) method is introduced. The extension, abbreviated as SF-XCIS, includes all
      configurations in which no more than one virtual level of the high spin triplet
      reference becomes occupied and no more than one doubly occupied level becomes
      vacant. The number of such configurations is quadratic with molecule size, and
      the method is implemented in a direct algorithm whose cost scales in the same way
      with molecule size as CIS itself, thus permitting applications to large systems.
      Starting from a spin restricted triplet determinant, SF-XCIS yields spin-pure
      singlet, triplet, and quintet states, and treats both half-occupied reference
      orbitals in a fully balanced way to allow application to strongly correlated
      problems. Tests on bond dissociation in the HF molecule, the torsional potential
      of ethylene, and excited states of polyenes show encouraging improvements using
      SF-XCIS compared to SF-CIS and a previously suggested extension, the spin
      complete CIS model.

PMID- 18715049
TI  - Adiabatic connection forms in density functional theory: H2 and the He
      isoelectronic series.
AB  - Full configuration interaction (FCI) data are used to quantify the accuracy of
      approximate adiabatic connection (AC) forms in describing two challenging
      problems in density functional theory--the singlet ground state potential energy
      curve of H(2) in a restricted formalism and the energies of the helium
      isoelectronic series, H(-) to Ne(8+). For H(2), an exponential-based form yields
      a potential energy curve that is virtually indistinguishable from the FCI curve,
      eliminating the unphysical barrier to dissociation observed previously with a
      [1,1]-Pade-based form and with the random phase approximation. For the helium
      isoelectronic series, the Pade-based form gives the best overall description,
      followed by the exponential form, with errors that are orders of magnitude
      smaller than those from a standard hybrid functional. Particular attention is
      paid to the limiting behavior of the AC forms with increasing bond distance in
      H(2) and increasing atomic number in the isoelectronic series; several forms
      describe both limits correctly. The study illustrates the very high quality
      results that can be obtained using exchange-correlation functionals based on
      simple AC forms, when near-exact data are used to determine the parameters in the
      forms.

PMID- 18715050
TI  - On a partial differential equation method for determining the free energies and
      coexisting phase compositions of ternary mixtures from light scattering data.
AB  - In this paper we present a method for determining the free energies of ternary
      mixtures from light scattering data. We use an approximation that is appropriate
      for liquid mixtures, which we formulate as a second-order nonlinear partial
      differential equation. This partial differential equation (PDE) relates the
      Hessian of the intensive free energy to the efficiency of light scattering in the
      forward direction. This basic equation applies in regions of the phase diagram in
      which the mixtures are thermodynamically stable. In regions in which the mixtures
      are unstable or metastable, the appropriate PDE is the nonlinear equation for the
      convex hull. We formulate this equation along with continuity conditions for the
      transition between the two equations at cloud point loci. We show how to
      discretize this problem to obtain a finite-difference approximation to it, and we
      present an iterative method for solving the discretized problem. We present the
      results of calculations that were done with a computer program that implements
      our method. These calculations show that our method is capable of reconstructing
      test free energy functions from simulated light scattering data. If the cloud
      point loci are known, the method also finds the tie lines and tie triangles that
      describe thermodynamic equilibrium between two or among three liquid phases. A
      robust method for solving this PDE problem, such as the one presented here, can
      be a basis for optical, noninvasive means of characterizing the thermodynamics of
      multicomponent mixtures.

PMID- 18715051
TI  - Building Markov state models along pathways to determine free energies and rates
      of transitions.
AB  - An efficient method is proposed for building Markov models with discrete states
      able to accurately describe the slow relaxation of a complex system with two
      stable conformations. First, the reaction pathway described by a set of
      collective variables between the two stable states is determined using the string
      method with swarms of trajectories. Then, short trajectories are initiated at
      different points along this pathway to build the state-to-state transition
      probability matrix. It is shown, using a model system, how this strategy makes it
      possible to use trajectories that are significantly shorter than the slowest
      relaxation time to efficiently build a reliable and accurate Markov model.
      Extensions of the method to multiple pathways, as well as some common pitfalls
      arising from poorly relaxed paths or an inappropriate choice of collective
      variables, are illustrated and discussed.

PMID- 18715052
TI  - Developing ab initio quality force fields from condensed phase quantum
      mechanics/molecular-mechanics calculations through the adaptive force matching
      method.
AB  - A new method called adaptive force matching (AFM) has been developed that is
      capable of producing high quality force fields for condensed phase simulations.
      This procedure involves the parametrization of force fields to reproduce ab
      initio forces obtained from condensed phase quantum-mechanics/molecular-mechanics
      (QM/MM) calculations. During the procedure, the MM part of the QM/MM is
      iteratively improved so as to approach ab initio quality. In this work, the AFM
      method has been tested to parametrize force fields for liquid water so that the
      resulting force fields reproduce forces calculated using the ab initio MP2 and
      the Kohn-Sham density functional theory with the Becke-Lee-Yang-Parr (BLYP) and
      Becke three-parameter LYP (B3LYP) exchange correlation functionals. The AFM force
      fields generated in this work are very simple to evaluate and are supported by
      most molecular dynamics (MD) codes. At the same time, the quality of the forces
      predicted by the AFM force fields rivals that of very expensive ab initio
      calculations and are found to successfully reproduce many experimental
      properties. The site-site radial distribution functions (RDFs) obtained from MD
      simulations using the force field generated from the BLYP functional through AFM
      compare favorably with the previously published RDFs from Car-Parrinello MD
      simulations with the same functional. Technical aspects of AFM such as the
      optimal QM cluster size, optimal basis set, and optimal QM method to be used with
      the AFM procedure are discussed in this paper.

PMID- 18715053
TI  - Density functional restricted-unrestricted approach for nonlinear properties:
      application to electron paramagnetic resonance parameters of square planar copper
      complexes.
AB  - The density functional restricted-unrestricted approach for treatments of spin
      polarization effects in molecular properties using spin restricted Kohn-Sham
      theory has been extended from linear to nonlinear properties. It is shown that
      the spin polarization contribution to a nonlinear property has the form of a
      quadratic response function that includes the zero-order Kohn-Sham operator, in
      analogy to the lower order case where the spin polarization correction to an
      expectation value has the form of a linear response function. The developed
      approach is used to formulate new schemes for computation of electronic g-tensors
      and hyperfine coupling constants, which include spin polarization effects within
      the framework of spin restricted Kohn-Sham theory. The proposed computational
      schemes are in the present work employed to study the spin polarization effects
      on electron paramagnetic resonance spin Hamiltonian parameters of square planar
      copper complexes. The obtained results indicate that spin polarization gives rise
      to sizable contributions to the hyperfine coupling tensor of copper in all
      investigated complexes, while the electronic g-tensors of these complexes are
      only marginally affected by spin polarization and other factors, such as choice
      of exchange-correlation functional or molecular structures, will have more
      pronounced impact on the accuracy of the results.

PMID- 18715054
TI  - Path integral calculation of free energies: quantum effects on the melting
      temperature of neon.
AB  - The path integral formulation has been combined with several methods to determine
      free energies of quantum many-body systems, such as adiabatic switching and
      reversible scaling. These techniques are alternatives to the standard
      thermodynamic integration method. A quantum Einstein crystal is used as a model
      to demonstrate the accuracy and reliability of these free energy methods in
      quantum simulations. Our main interest focuses on the calculation of the melting
      temperature of Ne at ambient pressure, taking into account quantum effects in the
      atomic dynamics. The free energy of the solid was calculated by considering a
      quantum Einstein crystal as reference state, while for the liquid, the reference
      state was defined by the classical limit of the fluid. Our findings indicate
      that, while quantum effects in the melting temperature of this system are small,
      they still amount to about 6% of the melting temperature, and are therefore not
      negligible. The particle density as well as the melting enthalpy and entropy of
      the solid and liquid phases at coexistence is compared to results obtained in the
      classical limit and also to available experimental data.

PMID- 18715055
TI  - Optimization of augmentation functions for correlated calculations of spin-spin
      coupling constants and related properties.
AB  - A new hierarchy of augmented basis sets optimized for the calculation of
      molecular properties such as indirect spin-spin coupling constants is presented.
      Based on the Dunning hierarchy of cc-pVXZ (X = D, T, Q, and 5) basis sets
      augmentation functions with tight exponents have been optimized for coupled
      cluster calculations of indirect spin-spin coupling constants. The optimal
      exponents for these tight functions have been obtained by optimizing the sum of
      the absolute values of all contributions to the coupling constant. On the basis
      of a series of test cases (CO, HF, N(2), F(2), H(2)O, NH(3), and CH(4)) we
      propose a set of tight s, p, and d functions to be added to the uncontracted
      Dunning basis sets, and, subsequently, to recontract. The resulting ccJ-pVXZ (X =
      D, T, Q, and 5) basis sets demonstrate excellent cost efficiency in benchmark
      calculations. These new basis sets should generally be applicable for the
      calculation of spin-spin coupling constants and other properties that have a
      strong dependence on powers of 1r or even contain a delta distribution for
      correlated ab initio methods.

PMID- 18715056
TI  - Restoring the size consistency of multireference configuration interactions
      through class dressings: applications to ground and excited states.
AB  - The present paper presents a revised version of a size-consistency correction to
      the multireference configuration interaction techniques previously proposed by
      Szalay et al. [J. Phys. Chem. 100, 6288 (1996)]. The method assumes a complete
      active space reference space and separates the nonreference determinants in
      several classes according to their number of inactive holes and particles. The
      correction is formulated as a dressing of the diagonal energies of these
      determinants, which depends on their class, as originally proposed by Ruttink et
      al. [J. Chem. Phys. 94, 7212 (1991)]. The exclusion principle violating
      corrections are evaluated through a simple counting of the various excitation
      processes which remain possible on each class. The efficiency of the method has
      been tested on a series of multireference problems for which full configuration
      interaction results are available (OH(2) bond breaking, Be insertion in H(2),
      excited states of CH(2)). The dressing of a given state not only provides
      excellent results for this state but also provides accurate excited roots. The
      efficiency of state-specific dressings is dramatic. The adaptation of this
      proposal to difference-dedicated configuration interactions can be extremely
      fruitful, as illustrated in the calculation of the 1 (1)A(g)-1(1)B(u)(pi->pi(*))
      transition energy of the trans-butadiene molecule.

PMID- 18715057
TI  - Closed-shell coupled-cluster theory with spin-orbit coupling.
AB  - A two-component closed-shell coupled-cluster (CC) approach using relativistic
      effective core potentials with spin-orbit coupling included in the post-Hartree
      Fock treatment is proposed and implemented at the CC singles and doubles (CCSD)
      level as well as at the CCSD level augmented by a perturbative treatment of
      triple excitations [CCSD(T)]. The latter invokes as an additional approximation
      the neglect of the occupied-occupied and virtual-virtual blocks of the spin-orbit
      coupling matrix in order to avoid the iterative N(7) steps in the treatment of
      triple excitations. The computational effort of the implemented two-component CC
      methods is about 10-15 times that of its corresponding nonrelativistic
      counterpart, which needs to be compared to the by a factor of 32 higher cost for
      fully relativistic schemes and schemes with spin-orbit coupling included already
      at the Hartree-Fock self-consistent field (HF-SCF) level. This substantial
      computational saving is due to the use of real molecular orbitals and real two
      electron integrals. Results on 5p-, 6p-, and 7p-block element compounds show that
      the bond lengths and harmonic frequencies obtained with the present two-component
      CCSD method agree well with those computed with the CCSD approach including spin
      orbit coupling at the HF-SCF level even for the 7p-block element compounds. As
      for the CCSD(T) approach, high accuracy for 5p- and 6p-block element compounds is
      retained. However, the difference in bond lengths and harmonic frequencies
      becomes somewhat more pronounced for the 7p-block element compounds.

PMID- 18715058
TI  - Molecular-orbital-free algorithm for excited states in time-dependent
      perturbation theory.
AB  - A nonlinear conjugate gradient optimization scheme is used to obtain excitation
      energies within the random phase approximation (RPA). The solutions to the RPA
      eigenvalue equation are located through a variational characterization using a
      modified Thouless functional, which is based upon an asymmetric Rayleigh
      quotient, in an orthogonalized atomic orbital representation. In this way, the
      computational bottleneck of calculating molecular orbitals is avoided. The
      variational space is reduced to the physically-relevant transitions by
      projections. The feasibility of an RPA implementation scaling linearly with
      system size N is investigated by monitoring convergence behavior with respect to
      the quality of initial guess and sensitivity to noise under thresholding, both
      for well- and ill-conditioned problems. The molecular-orbital-free algorithm is
      found to be robust and computationally efficient, providing a first step toward
      large-scale, reduced complexity calculations of time-dependent optical properties
      and linear response. The algorithm is extensible to other forms of time-dependent
      perturbation theory including, but not limited to, time-dependent density
      functional theory.

PMID- 18715059
TI  - Dihydrogen bond cooperativity in (HCCBeH)n clusters.
AB  - A theoretical study has been carried out on the clusters formed by the
      association of ethynylhydroberyllium (HC[triple bond]CBeH) monomers. The monomer
      presents a linear disposition with a dipole moment of 0.94 D. Clusters from two
      to six monomers have been calculated for three different configurations (linear,
      cyclic with dihydrogen bonds, and cyclic with hydrogen bonds to the pi-cloud),
      the third one being the most stable. The electronic properties of the clusters
      have been analyzed by means of the atoms in molecules and natural bond orbitals
      methodologies. Cooperative effects, similar to the ones described for standard
      hydrogen bonded clusters, are observed in those configurations where dihydrogen
      bonds are the main interacting force.

PMID- 18715060
TI  - Perturbative calculation of Franck-Condon integrals: new hints for a rational
      implementation.
AB  - Perturbative approaches to the mode mixing effects in the calculation of Franck
      Condon integrals are analyzed and discussed. The zero order multidimensional
      Franck-Condon integrals are factorized into products of one-dimensional ones, so
      that recurrence relations can be used without need of storing a huge number of
      data. Calculations on model systems show that at the second order of
      perturbation, the method gives results in very good agreement with the exact
      ones, even in the case of significantly large Duschinsky effect. The accuracy of
      the results can be substantially improved by grouping together all those modes
      which are strongly mixed with each other, usually a few ones, for which Franck
      Condon integrals can be computed exactly, and using the perturbative approach for
      treating the smaller mixing between all the other modes.

PMID- 18715061
TI  - Dual descriptors within the framework of spin-polarized density functional
      theory.
AB  - Spin-polarized density functional theory (SP-DFT) allows both the analysis of
      charge-transfer (e.g., electrophilic and nucleophilic reactivity) and of spin
      polarization processes (e.g., photophysical changes arising from electron
      transitions). In analogy with the dual descriptor introduced by Morell et al. [J.
      Phys. Chem. A 109, 205 (2005)], we introduce new dual descriptors intended to
      simultaneously give information of the molecular regions where the spin
      polarization process linking states of different multiplicity will drive electron
      density and spin density changes. The electronic charge and spin rearrangement in
      the spin forbidden radiative transitions S(0)-->T(n,pi(*)) and S(0)-->T(pi,pi(*))
      in formaldehyde and ethylene, respectively, have been used as benchmark examples
      illustrating the usefulness of the new spin-polarization dual descriptors. These
      quantities indicate those regions where spin-orbit coupling effects are at work
      in such processes. Additionally, the qualitative relationship between the
      topology of the spin-polarization dual descriptors and the vertical singlet
      triplet energy gap in simple substituted carbene series has been also discussed.
      It is shown that the electron density and spin density rearrangements arise in
      agreement with spectroscopic experimental evidence and other theoretical results
      on the selected target systems.

PMID- 18715063
TI  - Ab initio and direct dynamics study of the reaction of Cl atoms with HOCO.
AB  - The reaction of Cl with HOCO has been examined using the coupled-cluster method
      to locate and optimize the critical points on the ground-state potential energy
      surface. The results show that the reaction produces the HCl and CO(2) products
      as experimentally observed. The reaction occurs via a HOC(O)Cl intermediate with
      an estimated heat of formation of -97.8+/-2.0 kcal/mol. A direct ab initio
      dynamics method has been used to provide insight into the reaction mechanisms and
      to determine the thermal rate coefficients in the temperature range of 200-600 K.
      At room temperature, the thermal rate coefficient is predicted to be 3.0x10(-11)
      cm(3) molecule(-1) s(-1) with an activation energy of -0.2 kcal/mol. Two kinds of
      reactive trajectories are found. One kind proceeds through short-lived HOC(O)Cl
      complexes with a lifetime of 310 fs while the other kind occurs via longer-lived
      intermediates with a lifetime of 1.9 ps.

PMID- 18715062
TI  - Algorithmic dimensionality reduction for molecular structure analysis.
AB  - Dimensionality reduction approaches have been used to exploit the redundancy in a
      Cartesian coordinate representation of molecular motion by producing low
      dimensional representations of molecular motion. This has been used to help
      visualize complex energy landscapes, to extend the time scales of simulation, and
      to improve the efficiency of optimization. Until recently, linear approaches for
      dimensionality reduction have been employed. Here, we investigate the efficacy of
      several automated algorithms for nonlinear dimensionality reduction for
      representation of trans, trans-1,2,4-trifluorocyclo-octane conformation--a
      molecule whose structure can be described on a 2-manifold in a Cartesian
      coordinate phase space. We describe an efficient approach for a deterministic
      enumeration of ring conformations. We demonstrate a drastic improvement in
      dimensionality reduction with the use of nonlinear methods. We discuss the use of
      dimensionality reduction algorithms for estimating intrinsic dimensionality and
      the relationship to the Whitney embedding theorem. Additionally, we investigate
      the influence of the choice of high-dimensional encoding on the reduction. We
      show for the case studied that, in terms of reconstruction error root mean square
      deviation, Cartesian coordinate representations and encodings based on interatom
      distances provide better performance than encodings based on a dihedral angle
      representation.

PMID- 18715064
TI  - Calculation of the transport and relaxation properties of methane. I. Shear
      viscosity, viscomagnetic effects, and self-diffusion.
AB  - Transport properties of pure methane gas have been calculated in the rigid-rotor
      approximation using the recently proposed intermolecular potential energy
      hypersurface [R. Hellmann et al., J. Chem. Phys. 128, 214303 (2008)] and the
      classical-trajectory method. Results are reported in the dilute-gas limit for
      shear viscosity, viscomagnetic coefficients, and self-diffusion in the
      temperature range of 80-1500 K. Compared with the best measurements, the
      calculated viscosity values are about 0.5% too high at room temperature, although
      the temperature dependence of the calculated values is in very good agreement
      with experiment between 210 and 390 K. For the shear viscosity, the calculations
      indicate that the corrections in the second-order approximation and those due to
      the angular-momentum polarization are small, less than 0.7%, in the temperature
      range considered. The very good agreement of the calculated values with the
      experimental viscosity data suggests that the rigid-rotor approximation should be
      very reasonable for the three properties considered. In general, the agreement
      for the other measured properties is within the experimental error.

PMID- 18715065
TI  - Exact state-to-state quantum dynamics of the F + HD --> HF(v' = 2) + D reaction
      on model potential energy surfaces.
AB  - In this paper, we present the results of a theoretical investigation on the
      dynamics of the title reaction at collision energies below 1.2 kcal/mol using
      rigorous quantum reactive scattering calculations. Vibrationally resolved
      integral and differential cross sections, as well as product rotational
      distributions, have been calculated using two electronically adiabatic potential
      energy surfaces, developed by us on the basis of semiempirical modifications of
      the entrance channel. In particular, we focus our attention on the role of the
      exothermicity and of the exit channel region of the interaction on the
      experimental observables. From the comparison between the theoretical results,
      insight about the main mechanisms governing the reaction is extracted, especially
      regarding the bimodal structure of the HF(v = 2) nascent rotational state
      distributions. A good overall agreement with molecular beam scattering
      experiments has been obtained.

PMID- 18715066
TI  - A simulation of the photoelectron spectrum of pyrazolide.
AB  - Building on previous theoretical and spectroscopic studies of the pyrazolyl
      radical, a new three-state quasidiabatic Hamiltonian is reported which reproduces
      not only the equilibrium geometries and harmonic frequencies of the nominal X
      (2)A(2) state and low-lying A (2)B(1) excited state, but also the minimum energy
      points on the lowest two-state (X (2)A(2), A (2)B(1)) and three-state (X (2)A(2),
      A (2)B(1), B (2)B(2)) seams of conical intersection. The three-state Hamiltonian
      includes all terms through second order in both the diagonal and off-diagonal
      blocks. Its construction is accomplished in two steps. First, a nascent
      Hamiltonian, centered at the lowest energy two-state conical intersection, is
      determined using ab initio gradients and derivative couplings. Then, the nascent
      Hamiltonian is improved by optimizing selected contributions to the second-order
      coefficients to better reproduce relevant minima and harmonic frequencies. This
      Hamiltonian is then expressed in a basis tailored to describe the neutral states
      of interest under the multimode vibronic coupling approximation. The vibronic
      Hamiltonian is diagonalized to obtain negative ion photoelectron spectra for
      pyrazolide-h(3) and the completely deuterated analog pyrazolide-d(3). The
      resultant spectra, determined employing vibronic Hamiltonians as large as 500
      million terms, compare favorably to recent theoretical and spectroscopic results
      for pyrazolyl-d(3) and to spectroscopic results for pyrazolyl-h(3), for which no
      reliable simulations had been available.

PMID- 18715067
TI  - Argon cluster-mediated isolation and vibrational spectra of peroxy and nominally
      D(3h) isomers of CO3(-) and NO3(-).
AB  - Vibrational predissociation spectra are reported for two isomeric forms of the
      gas-phase ions, CO(3)(-) and NO(3)(-). The peroxy forms, (OOCO(-) and OONO(-))
      were isolated using an Ar-mediated synthetic scheme involving exchange of CO and
      NO for the more weakly bound Ar ligands in O(2)(-)Ar(m) clusters, while the forms
      based on a central heteroatom (CO(3)(-) and NO(3)(-)) were generated by electron
      impact on CO(2) and HNO(3) vapor. The simple two-band spectrum of OOCO(-)
      indicates that it is best described as the O(2)(-) x CO ion-molecule complex,
      whereas the covalently bound CO(3)(-) form yields a much more complicated
      vibrational spectrum with bands extending out to 4000 cm(-1). In contrast, the
      NO(3)(-) ion yields a simple spectrum with only one transition as expected for
      the antisymmetric NO stretching fundamental of a species with D(3h) structure.
      The spectrum of the peroxynitrite isomer, OONO(-), displays intermediate
      complexity that can be largely understood in the context of fundamentals
      associated with its cis and trans structures previously characterized in an Ar
      matrix.

PMID- 18715068
TI  - Theoretical determination of rate constants for vibrational relaxation and
      reaction of OH(X 2Pi, v = 1) with O(3P) atoms.
AB  - Collisions of the vibrationally excited OH(v = 1) molecule with atomic oxygen are
      investigated theoretically using a coupled-states, statistical capture (CS-ST)
      model. Vibrational relaxation can occur by inelastic scattering, and the
      vibrationally excited molecule can also be removed by reaction to form O(2) in
      both the ground (X (3)Sigma(g)(-)) and first excited (a (1)Delta(g)) state. In
      the former case, reaction occurs on the lowest potential energy surface of
      (2)A(") symmetry, and, in the latter case, by reaction on the lowest potential
      energy surface of (2)A(') symmetry. We report new ab initio potential energy
      surfaces for both these states in the product and reactant regions necessary for
      application of the coupled-states, statistical method. Comparison with exact,
      reactive scattering calculations within the J-shifting approximation indicate
      that the CS-ST rate constants for removal of OH(v = 1) can be expected to be
      reasonably accurate. Our calculated rate constants at 300 K agree well with the
      experimental results of Khachatrian and Dagdigian [Chem. Phys. Lett. 415, 1
      (2005)]. Reaction to yield O(2) (X (3)Sigma(g)(-)) is the dominant removal
      pathway. At subthermal temperatures, the rate constants for the various
      vibrational quenching processes all increase down to T approximately = 60 K and
      then decrease at lower temperature.

PMID- 18715069
TI  - Extracting the polarizability anisotropy from the transient alignment of HBr.
AB  - We use 40 fs, 780 nm laser pulses to transiently align HBr molecules. We study
      the temporal dynamics of the resultant rotational wavepacket to gain insight into
      the electronic properties of the molecule. We show that the HBr polarization
      anisotropy can be extracted by comparing the time dependence of the HBr alignment
      with both the analogous alignment behavior of N(2) and the predictions of a rigid
      rotor model.

PMID- 18715070
TI  - Negative ions of nitroethane and its clusters.
AB  - Valence and dipole-bound negative ions of the nitroethane (NE) molecule and its
      clusters are studied using photoelectron spectroscopy (PES), Rydberg electron
      transfer (RET) techniques, and ab initio methods. Valence adiabatic electron
      affinities (EA(a)s) of NE, C(2)H(5)NO(2), and its clusters, (C(2)H(5)NO(2))(n),
      n=2-5, are estimated using vibrationally unresolved PES to be 0.3+/-0.2 eV (n=1),
      0.9+/-0.2 eV (n=2), 1.5+/-0.2 eV (n=3), 1.9+/-0.2 eV (n=4), and 2.1+/-0.2 eV
      (n=5). These energies were then used to determine stepwise anion-neutral
      solvation energies and compared with previous literature values. Vertical
      detachment energies for (C(2)H(5)NO(2))(n)(-) were also measured to be 0.92+/
      0.10 eV (n=1), 1.63+/-0.10 eV (n=2), 2.04+/-0.10 eV (n=3), and 2.3+/-0.1 eV
      (n=4). RET experiments show that Rydberg electrons can be attached to NE both as
      dipole-bound and valence bound anion states. The results are similar to those
      found for nitromethane (NM), where it was argued that the diffuse dipole state
      act as a "doorway state" to the more tightly bound valence anion. Using previous
      models for relating the maximum in the RET dependence of the Rydberg effective
      principle number n(max)(*), the dipole-bound electron affinity is predicted to be
      approximately 25 meV. However, a close examination of the RET cross section data
      for NE and a re-examination of such data for NM finds a much broader dependence
      on n(*) than is seen for RET in conventional dipole bound states and, more
      importantly, a pronounced [l] dependence is found in n(max)(*) (n(max)(*)
      increases with [l]). Ab initio calculations agree well with the experimental
      results apart from the vertical electron affinity value associated with the
      dipole bound state which is predicted to be 8 meV. Moreover, the calculations
      help to visualize the dramatic difference in the distributions of the excess
      electron for dipole-bound and valence states, and suggest that NE clusters form
      only anions where the excess electron localizes on a single monomer.

PMID- 18715071
TI  - Calculations of static dipole polarizabilities of alkali dimers: prospects for
      alignment of ultracold molecules.
AB  - The rapid development of experimental techniques to produce ultracold alkali
      molecules opens the ways to manipulate them and to control their dynamics using
      external electric fields. A prerequisite quantity for such studies is the
      knowledge of their static dipole polarizability. In this paper, we computed the
      variations with internuclear distance and with vibrational index of the static
      dipole polarizability components of all homonuclear alkali dimers including
      Fr(2), and of all heteronuclear alkali dimers involving Li to Cs, in their
      electronic ground state and in their lowest triplet state. We use the same
      quantum chemistry approach as in our work on dipole moments [Aymar and Dulieu, J.
      Chem. Phys. 122, 204302 (2005)], based on pseudopotentials for atomic core
      representation, Gaussian basis sets, and effective potentials for core
      polarization. Polarizabilities are extracted from electronic energies using the
      finite-field method. For the heaviest species Rb(2), Cs(2), and Fr(2) and for all
      heteronuclear alkali dimers, such results are presented for the first time. The
      accuracy of our results on atomic and molecular static dipole polarizabilities is
      discussed by comparing our values with the few available experimental data and
      elaborate calculations. We found that for all alkali pairs, the parallel and
      perpendicular components of the ground state polarizabilities at the equilibrium
      distance R(e) scale as (R(e))(3), which can be related to a simple electrostatic
      model of an ellipsoidal charge distribution. Prospects for possible alignment and
      orientation effects with these molecules in forthcoming experiments are
      discussed.

PMID- 18715072
TI  - The structural and electronic properties of In(n)N(n = 1-13) clusters.
AB  - The structural and electronic properties of In(n)N(n=1-13) clusters have been
      investigated by density-functional theory with the generalized gradient
      approximation. The results indicate that the equilibrium structures of In(n)N are
      linear for n=1,2, planar for n=3-5, and three dimensional for n=6-13. Maximum
      peaks were observed for In(n)N clusters at n=3,7,9 on the size dependence for
      second-order energy difference. These imply that these clusters possess
      relatively higher stability, which is consistent with the case of binding energy
      per atom. Moreover, the results show that the bonding in small In(n)N clusters
      has a little ionic character by Mulliken population analysis. The energy gap
      between the highest occupied and lowest unoccupied molecular orbitals, the
      vertical ionization potential and electron vertical affinity (VIP and VEA) form
      an even-odd alternating pattern with increasing cluster size. In general, the VIP
      tends to lower as the cluster size increases, while the VEA tends to increase as
      the cluster size increases.

PMID- 18715073
TI  - Experimental and theoretical characterization of MSi16(-), MGe16(-), MSn16(-),
      and MPb16(-) (M = Ti, Zr, and Hf): the role of cage aromaticity.
AB  - Silicon (Si), germanium (Ge), tin (Sn), and lead (Pb) clusters mixed with a group
      4 transition metal atom [M = titanium (Ti), zirconium (Zr), and hafnium (Hf)]
      were generated by a dual-laser vaporization method, and their properties were
      analyzed by means of time-of-flight mass spectroscopy and anion photoelectron
      spectroscopy together with theoretical calculations. In the mass spectra, mixed
      neutral clusters of MSi(16), MGe(16), and MSn(16) were produced specifically, but
      the yield of MPb(16) was low. The anion photoelectron spectra revealed that
      MSi(16), MGe(16), and MSn(16) neutrals have large highest occupied molecular
      orbital-lowest unoccupied molecular orbital gaps of 1.5-1.9 eV compared to those
      of MPb(16) (0.8-0.9 eV), implying that MSi(16), MGe(16), and MSn(16) are
      evidently electronically stable clusters. Cage aromaticity appears to be an
      important determinant of the electronic stability of these clusters: Calculations
      of nucleus-independent chemical shifts (NICSs) show that Si(16)(4-), Ge(16)(4-),
      and Sn(16)(4-) have aromatic characters with negative NICS values, while Pb(16)(4
      ) has an antiaromatic character with a positive NICS value.

PMID- 18715074
TI  - Ion-pair dissociation of N2O in the 16.25-16.41 eV: dynamics and electronic
      structure.
AB  - The ion-pair dissociation dynamics of N(2)O -->(XUV) N(2)(+)(X (2)Sigma(g)(+), v)
      + O(-)((2)P(j)) at 16.248, 16.271, 16.389, and 16.411 eV have been studied using
      the velocity map imaging method and tunable XUV laser. The electronic structures
      of the ion-pair states have been studied by employing the ab initio quantum
      chemical calculation. The translational energy distributions and the angular
      distributions of the photofragments have been measured. The results show that
      about 40% of available energies are transformed into the translational energies,
      and the first excited vibrational states are populated most strongly for all four
      excitation energies. The anisotropy parameters beta are approximately 1. The ab
      initio calculations at the level of CASSCF6-311++g(3df) show that the equilibrium
      geometries of the ion-pair states are nonlinear with bond lengths R(N-N) = 1.10
      A, R(N-O) = 2.15 A, and bond angle N-N-O = 103 degrees, respectively. The ion
      pair states are formed by electron migration from the bonding sigma orbital of
      N[triple bond]N to the antibonding sigma orbital localized primarily on the O
      atom. Combining the experimental and theoretical results, it is concluded that
      the ion-pair dissociation occurs via predissociation of Rydberg states with
      (1)Sigma(+) symmetry, which converges to the ion-core N(2)O(+)(A (2)Sigma(+)).

PMID- 18715075
TI  - H2, HD, and D2 inside C60: coupled translation-rotation eigenstates of the
      endohedral molecules from quantum five-dimensional calculations.
AB  - We have performed rigorous quantum five-dimensional (5D) calculations of the
      translation-rotation (T-R) energy levels and wave functions of H(2), HD, and D(2)
      inside C(60). This work is an extension of our earlier investigation of the
      quantum T-R dynamics of H(2)@C(60) [M. Xu et al., J. Chem. Phys. 128, 011101
      (2008)] and uses the same computational methodology. Two 5D intermolecular
      potential energy surfaces (PESs) were employed, differing considerably in their
      well depths and the degree of confinement of the hydrogen molecule. Our
      calculations revealed pronounced sensitivity of the endohedral T-R dynamics to
      the differences in the interaction potentials, and to the large variations in the
      masses and the rotational constants of H(2), HD, and D(2). The T-R levels vary
      significantly in their energies and ordering on the two PESs, as well as from one
      isotopomer to another. Nevertheless, they all display the same distinctive
      patterns of degeneracies, which can be qualitatively understood and assigned in
      terms the model which combines the isotropic three-dimensional harmonic
      oscillator, the rigid rotor, and the coupling between the orbital and the
      rotational angular momenta of H(2)/HD/D(2). The quantum number j associated with
      the rotation of H(2), HD, and D(2) was found to be a good quantum number for H(2)
      and D(2) on both PESs, while most of the T-R levels of HD exhibit strong mixing
      of two or more rotational basis functions with different j values.

PMID- 18715076
TI  - A computational study of metastable states of CO2+.
AB  - Extensive calculations of energies and lifetimes of vibronic and rovibronic
      states of the CO(2+) dication are performed using the electronic energy
      potentials and spin-orbit couplings published recently by Sedivcova et al. [J.
      Chem. Phys. 124, 214303 (2006)] and by Eland et al. [J. Phys. B 37, 3197 (2004)].
      Siegert quantization, bound-continuum configuration mixing, two-potential, and
      semiclassical methods are exploited in the calculations. Lifetimes for
      predissociation and tunneling, varying over a wide range, are determined,
      demonstrating a very good agreement between results yielded by the different
      methods. Dependence of the calculated predissociation characteristics (level
      widths and shifts) on the individual potentials and couplings is analyzed. The
      potentials of Sedivcova et al., especially the repulsive potential of the
      (3)Sigma(-) state, are found insufficiently accurate in the medium range of the
      internuclear distance to be useful in simulations of the decay of the lowest
      vibronic states of the ion, X (3)Pi(v = 0,1) and a (1)Sigma(+)(v = 0,1).
      Combining the potentials of Eland et al. with the SO couplings of Sedivcova et
      al. is demonstrated to provide the best description of metastability of the ion
      so far. Purely vibronic models constructed in this way give lifetimes in a
      reasonable agreement with all existing experimental values and estimates. The
      largest deviations, tau(expt)/tau(calc) approximately 20, occur in the X (3)Pi(v
      = 1,2) cases. Strong evidence is provided that accounting for rotational motion
      of nuclei, spin-uncoupling perturbations, and diagonal spin-orbit couplings can
      reduce these deviations substantially, approximately ten times. The
      predissociation lifetimes of the rovibronic states A (3)Sigma(0,1)(+)(Jv) are
      predicted to be, with no exception, more than 100 times shorter than radiative
      lifetimes of these states.

PMID- 18715077
TI  - Full dimensional time-dependent quantum dynamics study of the H + NH3 --> H2 +
      NH2 reaction.
AB  - A rigorous full dimensional time-dependent wave packet method has been developed
      for the reactive scattering between an atom and a tetra-atomic molecule. The
      method has been applied to the hydrogen abstraction reaction H+NH(3)-
      >H(2)+NH(2). Initial state-selected total reaction probabilities are investigated
      for the reactions from the ground vibrational state and from four excited
      vibrational states of ammonia. The total reaction probabilities from two lowest
      "tunneling doublets" due to the inversion barrier for the umbrella bending motion
      of NH(3) and from two pairs of doubly degenerate vibrational states of NH(3) are
      also inspected. Integral cross sections and rate constants are calculated for the
      reaction from the ground state with the centrifugal-sudden approximation. The
      calculated results are compared with those from the previous seven dimensional
      calculations [M. Yang and J. C. Corchado, J. Chem. Phys. 126, 214312 (2007)].
      This work shows that the full dimensional rate constants are a factor of 3 larger
      than the corresponding seven dimensional calculated values at T=200 K and are
      overall smaller than those obtained from the variational transition state theory
      in the whole temperature region. The work also reveals that nonreactive NH bonds
      of NH(3) cannot be treated as spectators due to the fact that three NH bonds are
      coupled with each other during the reaction process.

PMID- 18715078
TI  - Variational and diffusion Monte Carlo study of post-d group 13-17 elements.
AB  - We present ab initio calculations of atomic and molecular systems containing the
      first-, second-, and third-row post-d elements (Ga-Br, In-I, and Tl-At) using
      several methods including variational and diffusion Monte Carlo. In the quantum
      Monte Carlo calculations, we used the recent scalar-relativistic energy
      consistent Hartree-Fock pseudopotentials [M. Burkatzki et al., J. Chem. Phys.
      126, 234105 (2007)], which are nonsingular at the origin. For the first- and
      second-row elements, the calculated ionization energies and electron affinities
      are in excellent agreement with those obtained using CCSD(T) with large basis
      sets and with experiment after correcting approximately for spin-orbit effects.
      For the third-row elements, where relativistic effects cannot be adequately
      included by a simple j-averaging, the results are in excellent agreement with
      CCSD(T) energies obtained with a large (5-zeta) basis set. Benchmark calculations
      of the dissociation energies, vibration frequencies, and equilibrium bond lengths
      of several diatomic molecules including As(2), Br(2), Sb(2), and I(2) as well as
      the hydrides XH (X = Ga, Br, In, I, and At) are presented.

PMID- 18715079
TI  - Nitroxide spin exchange due to re-encounter collisions in a series of n-alkanes.
AB  - Bimolecular collisions between perdeuterated 2,2,6,6-tetramethyl-4-oxopiperidine
      l-oxyl molecules in three alkanes have been studied by measuring the electron
      paramagnetic resonance (EPR) spectral changes induced by spin exchange. We define
      an "encounter" to be a first-time collision followed by a series of re-encounters
      prior to the diffusing pair's escaping each other's presence. The present work
      stems from a recent proposal [B. L. Bales et al., J. Phys. Chem. A 107, 9086
      (2003)] that an unexpected linear dependence of the spin-exchange-induced EPR
      line shifts on spin-exchange frequency can be explained by re-encounters of the
      same probe pair during one encounter. By employing nonlinear least-squares
      fitting, full use of the information available from the spectral changes allows
      us to study encounters and re-encounters separately. The encounter rate constants
      appear to be dominated by hydrodynamic forces, forming a common curve for hexane,
      decane, and hexadecane when plotted against T/eta, where eta is the shear
      viscosity. Unexpectedly, encounters are not dependent on the ratio mu = a/a(s),
      where a and a(s) are the van der Waals radii of the nitroxide probe and the
      solvent, respectively. It is argued that the near coincidence of the resulting
      encounter rate constant with the hydrodynamic prediction is likely due to a near
      cancellation of terms in the general diffusion coefficient. Thus, the semblance
      of hydrodynamic behavior is coincidental rather than intrinsic. In contrast, the
      mean times between re-encounters do depend on the relative sizes of probe and
      solvent. For hexane at lower temperatures, the Stokes-Einstein equation
      apparently describes re-encounters well; however, at higher temperatures and for
      decane and hexadecane, departures from the hydrodynamic prediction become larger
      as mu becomes smaller. This is in qualitative agreement with the theory of
      microscopic diffusion of Hynes et al. [J. Chem. Phys. 70, 1456 (1979)]. These
      departures are well correlated with the free volume available in the solvent;
      thus, the mean times between re-encounters form a common curve when plotted
      versus the free volume. Because free volume is manifested macroscopically by the
      isothermal compressibility, it is expected and observed that the re-encounter
      rate also forms a common curve across all three solvents when plotted with
      respect to compressibility. The existence of a common curve for alkanes raises
      the prospect of using EPR to determine the compressibility of substances such as
      fossil fuels and biological membranes.

PMID- 18715080
TI  - 2D calculation of anharmonic OH vibrations in a layered hydroxide crystal.
AB  - Anharmonic vibrational frequencies for the Raman-active (A(1g)) and the IR-active
      (A(2u)) modes have been calculated for the LiOH crystal within a plane-wave
      density functional theory (DFT) framework. We find that a two-dimensional quantum
      mechanical vibrational approach, allowing for anharmonic coupling between
      symmetric and antisymmetric OH stretching modes, produces OH frequencies--both
      absolute frequencies and gas-to-solid frequency shifts--in good agreement with
      experiment. Remaining errors in the absolute frequencies are largely a
      consequence of the DFT model chosen. A one-dimensional normal-mode following
      vibrational treatment, on the other hand, fails to reproduce both absolute
      anharmonic frequencies and gas-to-solid frequency shifts.

PMID- 18715081
TI  - Isotope effects in liquid water by infrared spectroscopy. II. Factor analysis of
      the temperature effect on H2O and D2O.
AB  - Some 500 infrared (IR) spectra of light and heavy waters were obtained between 29
      and 93 degrees C in order to identify the species present in liquid water. Factor
      analysis of these gives two species for each type of water with their IR spectra
      and abundance curves. Using an orthogonalization procedure, we obtained the
      temperature factor limits of -22 and +118 degrees C (+/-5 degrees C) that we
      coined cold and hot factors, respectively. Within experimental error, these
      limits are the same for light and heavy waters. The spectra of the orthogonalized
      factors presented show a decrease of the OH (OD) stretch band integrated
      intensities of almost 36% from the cold to the hot factors. No "free" OH (OD)
      group is present or formed in the temperature ramp. This indicates that all water
      molecules in the bulk are made of an oxygen atom surrounded with four hydrogen
      atoms, two covalently bonded, and two hydrogen bonded. This is consistent with
      the previous study of mixtures of H(2)O and D(2)O [part I: J.-J. Max and C.
      Chapados, J. Chem. Phys. 116, 4626 (2002)]. To maintain the ordinary liquid
      within the limits of 0 and 100 degrees C at atmospheric pressure, a fraction of
      the cold and hot factors are necessary. With the spectra of the cold and hot
      factors and the abundance curves, one can generate the spectrum at any
      temperature between -22 and +118 degrees C of light and heavy liquid waters.

PMID- 18715082
TI  - Parallels between multiple population-period transient spectroscopy and
      multidimensional coherence spectroscopies.
AB  - We have recently shown that homogeneous and heterogeneous kinetics can be
      distinguished by experiments that compare the evolution of the population of a
      state over two time intervals [E. van Veldhoven et al., ChemPhysChem 8, 1761
      (2007)]. This paper elaborates on the analogy between these multiple population
      period transient spectroscopy (MUPPETS) experiments and more familiar
      spectroscopies based on the evolution of coherences. Using a modified inverse
      Laplace transform, a standard kinetics decay is re-expressed as a "rate
      spectrum." A nonexponential decay creates a linewidth in this spectrum.
      Mechanisms for line broadening in rate spectra are compared to those for line
      broadening in frequency-domain spectra. Homogeneous and heterogeneous kinetics
      are defined precisely and are shown to be the counterparts of homogeneous and
      inhomogeneous line broadenings in frequency-domain spectra. Homogeneous line
      broadening mechanisms are further divided into equilibrium and nonequilibrium
      mechanisms, with equilibrium mechanisms more prevalent in frequency spectra and
      nonequilibrium mechanisms more prevalent in rate spectra. Spectral
      representations of two-dimensional MUPPETS experiments are developed that are
      equivalent to two-dimensional coherence spectroscopies. In particular, spectra
      equivalent to hole-burning and to correlation spectra are defined. Frequency
      domain spectra are often modeled as an inhomogeneous distribution of identical
      homogeneous line shapes. A parallel homogeneous-heterogeneous model for kinetics
      is defined. Within this model, MUPPETS has sufficient information to completely
      separate the homogeneous and heterogeneous contributions to a nonexponential
      decay, even when the homogeneous contribution is nonexponential.

PMID- 18715083
TI  - Study of spatial correlations in a supercooled molecular system.
AB  - Spatial heterogeneities have been investigated in a supercooled system composed
      of diatomic molecules with an associated dipole moment by using the molecular
      dynamics simulation technique. Pair distribution functions of molecules with
      different mobilities have been evaluated, and it has been found that molecules
      belonging to the same dynamic domain are spatially correlated. Molecules with
      extremely large mobilities form larger clusters than those resulting from random
      statistics. These clusters are stringlike shaped. The mean cluster size displays
      a maximum at times between the ballistic and the diffusive regime, approximately
      at the end of the beta-relaxation zone. The value of this maximum increases upon
      cooling the system. An analogous profile has been observed for the characteristic
      cluster length when plotted against time. Agreement with Adam-Gibbs predictions
      has been encountered when considering these clusters as the basic dynamic units
      of the theory. For the extremely slow molecules, a cluster distribution has also
      been encountered. These clusters are smaller than the ones composed by fast
      molecules; they do not have a quasilinear geometry and no maximum is observed for
      their mean cluster size.

PMID- 18715084
TI  - Rotational dynamics and polymerization of C60 in C60-cubane crystals: a molecular
      dynamics study.
AB  - We report classical and tight-binding molecular dynamics simulations of the C(60)
      fullerene and cubane molecular crystal in order to investigate the intermolecular
      dynamics and polymerization processes. Our results show that, for 200 and 400 K,
      cubane molecules remain basically fixed, presenting only thermal vibrations,
      while C(60) fullerenes show rotational motions. Fullerenes perform "free"
      rotational motions at short times (approximately < 1 ps), small amplitude
      hindered rotational motions (librations) at intermediate times, and rotational
      diffusive dynamics at long times (approximately > 10 ps). The mechanisms
      underlying these dynamics are presented. Random copolymerizations among cubanes
      and fullerenes were observed when temperature is increased, leading to the
      formation of a disordered structure. Changes in the radial distribution function
      and electronic density of states indicate the coexistence of amorphous and
      crystalline phases. The different conformational phases that cubanes and
      fullerenes undergo during the copolymerization process are discussed.

PMID- 18715085
TI  - Origin of negative and dispersive features in anti-Stokes and resonance
      femtosecond stimulated Raman spectroscopy.
AB  - Femtosecond stimulated Raman spectroscopy is extended to probe ground state anti
      Stokes vibrational features. Off resonance, negative anti-Stokes features are
      seen that are the mirror image of the positive Stokes side spectra. On resonance,
      the observed dispersive lineshapes are dramatically dependent on the frequencies
      of the picosecond pump and femtosecond probe pulses used to generate the
      stimulated Raman spectra. These observations are explained by the contributions
      of the inverse Raman and hot luminescence four-wave mixing processes discussed by
      Sun et al. [J. Chem. Phys. 128, 144114 (2008)], which contribute to the overall
      femtosecond stimulated Raman signal.

PMID- 18715086
TI  - Chemical short-range order in liquid Al-Ni alloys.
AB  - The chemical short-range structure was studied in liquid Al-Ni alloys by x-ray
      absorption spectroscopy as a function of temperature and composition. A
      containerless technique, combining aerodynamic levitation and inductive heating,
      was used to position and melt the samples. The fluorescence yield x-ray
      absorption at the Ni K edge was measured by a multichannel solid-state Ge
      detector. The number of heteroatomic pairs around the scatterer is higher than
      for a homogeneous alloy.

PMID- 18715087
TI  - Orientational correlations in molecular liquid SnI4.
AB  - The total scattering structure factor of liquid tin tetraiodide (SnI(4)) has been
      interpreted by means of reverse Monte Carlo (RMC) modeling. From the sets of
      particle coordinates provided by RMC, which are consistent with experimental
      results within errors, partial radial distribution functions as well as
      correlation functions characterizing mutual orientations of molecules as a
      function of distance between molecular centers can be calculated. Interestingly
      and very much in contrast to liquids of symmetric XCl(4) molecules, the corner-to
      face (or "Apollo")-type orientation of neighboring molecules has a significant
      (about 20%) occurrence in liquid SnI(4). Via comparison with a reference system,
      obtained by hard sphere Monte Carlo simulation, we demonstrate that
      intermolecular two-body correlations in liquid SnI(4) are determined largely by
      excluded volume (steric) effects; that is, intermolecular two-body interactions
      play only a minor role. On the other hand, as it is manifested in the large
      difference between the reference and "real" systems in terms of the orientational
      correlations, higher order interactions are indispensable. This feature can
      explain the extremely rich phase behavior of SnI(4) at high pressures.

PMID- 18715088
TI  - Continuum percolation of long lifespan clusters in a simple fluid.
AB  - We present results on the percolation loci for chemical clusters and physical
      clusters of long lifespan. Chemical clusters are defined as sets of particles
      connected through particle-particle bonds that last for a given time tau.
      Physical clusters are sets of particles that remain close together at every
      instant for a given period of time tau. By using molecular dynamics simulations
      of a Lennard-Jones system we obtain the percolation loci at different values of
      tau as the lines in the temperature-density plane at which the system presents a
      spanning cluster in 50% of the configurations. We find that the percolation loci
      for chemical clusters shifts rapidly toward high densities as tau is increased.
      For moderate values of tau this line converges to the low-density branch of the
      liquid-solid coexistence curve. This implies that no stable chemical clusters can
      be found in the fluid phase. In contrast, the percolation loci for physical
      clusters tend to a limiting line, as tau tends to infinity, which is far from the
      liquid-solid transition line.

PMID- 18715089
TI  - Water/polymer interactions in poly(amidoamine) hydrogels by 1H nuclear magnetic
      resonance relaxation and magnetization transfer.
AB  - Hydrated cross-linked polymers belonging to the family of poly(amidoamine)s were
      investigated by high and low resolution (1)H nuclear magnetic resonance
      techniques in order to obtain information on water/polymer interactions in the
      swollen state. (1)H spin-spin and spin-lattice relaxation time analysis, as well
      as magnetization transfer experiments, indicated that water and polymer proton
      pools are essentially uncoupled, with water molecules diffusing fast within the
      hydrogel structure and exchanging between "bound" and free sites. For the polymer
      characterized by the highest cross-linking degree, there is strong evidence of a
      beadlike structure resulting in higher network rigidity and hydrogel micrometric
      heterogeneity.

PMID- 18715090
TI  - Quasibinary amorphous phase in a three-dimensional system of particles with
      repulsive-shoulder interactions.
AB  - We report a computer-simulation study of the equilibrium phase diagram of a three
      dimensional system of particles with a repulsive-step potential. Using free
      energy calculations, we have determined the equilibrium phase diagram of this
      system. At low temperatures, we observe a number of distinct crystal phases.
      However, under certain conditions the system undergoes a glass transition in a
      regime where the liquid appears thermodynamically stable. We argue that the
      appearance of this amorphous low-temperature phase can be understood by viewing
      this one-component system as a quasibinary mixture.

PMID- 18715091
TI  - Polarization and interactions of colloidal particles in ac electric fields.
AB  - Micrometer-sized polystyrene particles form two-dimensional crystals in
      alternating current (ac) electric fields. The induced dipole-dipole interaction
      is the dominant force that drives this assembly. We report measurements of forces
      between colloidal particles in ac electric fields using optical tweezers and find
      good agreement with the point dipole model. The magnitude of the pair interaction
      forces depends strongly on the bulk solution conductivity and decreases as the
      ionic strength increases. The forces also decrease with increasing field
      frequency. The salt and frequency dependences are consistent with double layer
      polarization with a characteristic relaxation frequency omega(CD) approximately
      a(2)/D, where a is the particle radius and D is the ion diffusivity. This enables
      us to reinterpret the order-disorder transition reported for micrometer-sized
      polystyrene particles [Lumsdon et al., Langmuir 20, 2108 (2004)], including the
      dependence on particle size, frequency, and ionic strength. These results provide
      a rational framework for identifying assembly conditions of colloidal particles
      in ac fields over a wide range of parameters.

PMID- 18715092
TI  - Femtosecond spectroscopy of solvated electrons from sodium-ammonia-d3 solutions:
      temperature jump versus local density jump.
AB  - The relaxation dynamics of solvated electrons from sodium-ammonia-d3 solutions
      was studied by femtosecond time-resolved near-infrared spectroscopy. The
      experimental pump-probe data reveal a pulse-width limited pump-induced redshift
      of the absorption spectrum of the ammoniated electron and a subsequent slower
      blueshift on a time scale of roughly 200 fs. The spectrotemporal response is
      interpreted using the nonadiabatic relaxation mechanism for cavity-bound solvated
      electrons in condensed phases. In particular, we develop a local density-jump
      model, which traces the dynamic spectrum back to a sequence of a pump-induced
      cavity expansion due to Pauli repulsion and a succeeding cavity contraction upon
      nonadiabatic return of the electron back to its ground state. Using the existing
      thermodynamic data of the solvent and experimental temperature and density
      dependent absorption spectra of metal-ammonia solutions, an overall increase in
      the interparticle distance within the solvent cavity of 25% is crudely estimated.
      The density-jump model is compared to the temperature-jump model we proposed
      previously for the femtosecond relaxation dynamics of metal-NH(3) solutions.

PMID- 18715093
TI  - Semiclassical initial value series representation in the continuum limit:
      application to vibrational relaxation.
AB  - A recently formulated continuum limit semiclassical initial value series
      representation (SCIVR) of the quantum dynamics of dissipative systems is applied
      to the study of vibrational relaxation of model harmonic and anharmonic
      oscillator systems. As is well known, the classical dynamics of dissipative
      systems may be described in terms of a generalized Langevin equation. The
      continuum limit SCIVR uses the Langevin trajectories as input, albeit with a
      quantum noise rather than a classical noise. Combining this development with the
      forward-backward form of the prefactor-free propagator leads to a tractable
      scheme for computing quantum thermal correlation functions. Here we present the
      first implementation of this continuum limit SCIVR series method to study two
      model problems of vibrational relaxation. Simulations of the dissipative harmonic
      oscillator system over a wide range of parameters demonstrate that at most only
      the first two terms in the SCIVR series are needed for convergence of the
      correlation function. The methodology is then applied to the vibrational
      relaxation of a dissipative Morse oscillator. Here, too, the SCIVR series
      converges rapidly as the first two terms are sufficient to provide the quantum
      mechanical relaxation with an estimated accuracy on the order of a few percent.
      The results in this case are compared with computations obtained using the
      classical Wigner approximation for the relaxation dynamics.

PMID- 18715094
TI  - Relaxation rate and scaling function of the critical system 3-methylpentane
      nitroethane-cyclohexane.
AB  - The critical system 3-methylpentane-nitroethane-cyclohexane (3-MP-NE-CH) has been
      investigated and compared to the limiting binary systems 3-MP-NE as well as NE-CH
      in order to study the degree of renormalization in the critical exponents of the
      ternary system. The solubility curves of the 3-MP-NE-CH system have been
      determined at various molar ratios of the nonpolar constituents in order to
      obtain the plait points as a function of mixture composition. At the col point
      (the mixture with the lowest transition temperature) and two further plait point
      compositions shear viscosity, dynamic light scattering, and frequency-dependent
      ultrasonic attenuation coefficient measurements have been performed as a function
      of temperature near the critical temperatures. The fluctuation correlation length
      and the relaxation rate of fluctuations display power law behavior as a function
      of reduced temperature, with universal critical exponents nu = 0.63 and nuZ(0) =
      1.928, respectively, as characteristic for binary critical mixtures. In
      conformity with the 3-MP-NE and NE-CH critical mixtures the scaling function in
      the ultrasonic spectra nicely agrees with the empirical scaling function of the
      Bhattacharjee-Ferrell dynamic scaling theory. Hence with respect to power laws
      and scaling the 3-MP-NE-CH system behaves like a quasibinary mixture. The
      individual amplitudes of the relaxation rate show a minimum at the col point
      composition, corresponding with a maximum in the background viscosity of the
      liquids. The amount of the adiabatic coupling constant g, derived from the
      amplitudes in the ultrasonic spectra, increases monotonously when going from NE
      CH (/g/ = 0.1) to 3-MP-NE (/g/ = 0.26).

PMID- 18715095
TI  - Structural and dynamical properties of ionic liquids: the influence of ion size
      disparity.
AB  - The influence of ion size disparity on structural and dynamical properties of
      ionic liquids is systematically investigated employing molecular dynamics
      simulations. Ion size ratios are varied over a realistic range (from 1:1 to 5:1)
      while holding other important molecular and system parameters fixed. In this way
      we isolate and identify effects that stem from size disparity alone. In strongly
      size disparate systems the larger species (cations in our model) tend to dominate
      the structure; the anion-anion distribution is largely determined by anion-cation
      correlations. The diffusion coefficients of both species increase, and the shear
      viscosity decreases with increasing size disparity. The influence of size
      disparity is strongest up to a size ratio of 3:1, then decreases, and by 5:1 both
      the diffusion coefficients and viscosity appear to be approaching limiting
      values. The conventional Stokes-Einstein expression for diffusion coefficients
      holds reasonably well for the cations but fails for the smaller anions as size
      disparity increases likely due to the neglect of strong anion-cation
      correlations. The electrical conductivity is not a simple monotonic function of
      size disparity; it first increases up to size ratios of 2:1, remains nearly
      constant until 3:1, then decreases such that the conductivities of the 1:1 and
      5:1 systems are similar. This behavior is traced to the competing influences of
      ion diffusion (enhancing) and ion densities (reducing) on conductivities at
      constant packing fraction. The temperature dependence of the transport properties
      is examined for the 1:1 and 3:1 systems. In accord with experiment, the
      temperature dependence of all transport properties is well represented by the
      Vogel-Fulcher-Tammann equation. The dependence of the diffusion coefficients on
      the temperature/viscosity ratio is well described by the fractional Stokes
      Einstein relation D proportional to (T/eta)(beta) with beta approximately = 0.8,
      consistent with the exponent observed for many molten inorganic salts.

PMID- 18715096
TI  - Dielectric process of space-charge polarization for an electrolytic cell with
      blocking electrodes.
AB  - The dielectric process of space-charge polarization for an electrolytic cell with
      blocking electrodes is simulated considering bound charges externally supplied to
      the electrodes. A numerical calculation is performed to determine the
      distribution of mobile charges under an ac field satisfying Poisson's equation in
      which the dielectric constant varies with frequency. An exact frequency-dependent
      curve of the complex dielectric constant is obtained by including the
      contribution of bound charges induced by the space-charge polarization itself in
      Poisson's equation at every frequency. The present model of the space-charge
      polarization enables one to correctly understand the experimental results on the
      complex dielectric constant of electrolytic cells in low-frequency regions.

PMID- 18715097
TI  - Transient hydroxyl formation from water on oxygen-covered Au(111).
AB  - We present evidence for the formation of transient hydroxyls from the reaction of
      water with atomic oxygen on Au(111) and investigate the effect of adsorbed oxygen
      on the hydrogen bonding of water. Water is evolved in peaks at 175 and 195 K in
      temperature programed reaction experiments following adsorption of water on
      oxygen-covered Au(111). The peak at 175 K is ascribed to sublimation of
      multilayers of water, whereas the peak at 195 K is associated with oxygen
      stabilized water or a water-hydroxyl surface complex. Infrared reflection
      absorption spectra are consistent with the presence of molecular water over the
      entire range of coverages studied, indicating that isolated stable hydroxyls are
      not formed. Isotopic exchange of adsorbed (16)O with H(2)(18)O following
      adsorption and subsequent temperature programed reaction, however, indicates that
      transient OH species are formed. The extent of oxygen exchange was considerable-
      up to 70%. The degree of oxygen exchange depends on the initial coverage of
      oxygen, the surface temperature when preparing oxygen adatoms, and the H(2)(18)O
      coverage. The hydroxyls are short-lived, forming and disproportionating multiple
      times before water desorption during temperature programed reaction. It was also
      found that chemisorbed oxygen is critical in the formation of hydroxyls and
      stabilizing water, whereas gold oxide does not contribute to these effects. These
      results identify transient hydroxyls as species that could play a critical role
      in oxidative chemical reactions on gold, especially in ambient water vapor. The
      crystallinity of adsorbed water also depended on the degree of surface ordering
      and chemical modification based on scanning tunneling microscopy and infrared
      spectra. These results demonstrate that oxidation of interfaces has a major
      impact on their interaction with water.

PMID- 18715098
TI  - Quantum molecular dynamics study of water on TiO2(110) surface.
AB  - The adsorption of water on perfect TiO(2)(110) surface is studied by quantum
      molecular dynamics simulation adopting a periodic model formed by five water
      molecules on a (5 x 1) surface unit cell of a five layer slab of TiO(2). The
      total simulation time is 3.2 ps. At about 1.3 ps, one water molecule dissociates
      with the help of other adsorbed waters and surface bridging oxygens. During the
      remaining 1.9 ps, the waters and OH groups vibrate, but no more dissociation or
      recombination is observed. By comparing recent experimental O1s photoemission (x
      ray photoelectron spectroscopy) spectra of H(2)O/TiO(2)(110) to the computed
      spectrum of the adsorbate in the configurations supplied by the molecular
      dynamics simulation, the observed peaks can be attributed to different oxygen
      species. The proposed assignment of the main spectral features supports the
      occurrence of partial water dissociation (approximately 20%) also on a perfect
      TiO(2) surface.

PMID- 18715099
TI  - Oligo(vinylidene fluoride) Langmuir-Blodgett films studied by spectroscopic
      ellipsometry and the density functional theory.
AB  - Thin films of amphiphilic vinylidene fluoride oligomers prepared by Langmuir
      Blodgett deposition on silicone substrates were investigated by comparing
      experimental and theoretical mid-infrared (IR) spectra. The experimental spectra
      were obtained using infrared spectroscopic ellipsometry. Theoretical spectra were
      calculated using density functional theory. Excellent correspondence of major IR
      bands in both data sets shows that the molecular backbone is oriented with the
      long axis normal to the substrate plane. This is in contrast to poly(vinylidene
      fluoride) LB films, in which the polymer chains are parallel to the substrate.

PMID- 18715100
TI  - Time dependent density functional theory study of the near-edge x-ray absorption
      fine structure of benzene in gas phase and on metal surfaces.
AB  - The near-edge x-ray absorption fine structure of benzene in the gas phase and
      adsorbed on the Au(111) and Pt(111) surfaces is studied with time dependent
      density functional theory. Excitation energies computed with hybrid exchange
      correlation functionals are too low compared to experiment. However, after
      applying a constant shift the spectra are in good agreement with experiment. For
      benzene on the Au(111) surface, two bands arising from excitation to the
      e(2u)(pi(*)) and b(2g)(pi(*)) orbitals of benzene are observed for photon
      incidence parallel to the surface. On Pt(111) surface, a broader band arises from
      excitation to benzene orbitals that are mixed with the surface and have both
      sigma(*)(Pt-C) and pi(*) characters.

PMID- 18715101
TI  - Optimal design of nanoplasmonic materials using genetic algorithms as a
      multiparameter optimization tool.
AB  - An optimal control approach based on multiple parameter genetic algorithms is
      applied to the design of plasmonic nanoconstructs with predetermined optical
      properties and functionalities. We first develop nanoscale metallic lenses that
      focus an incident plane wave onto a prespecified, spatially confined spot. Our
      results illustrate the mechanism of energy flow through wires and cavities. Next
      we design a periodic array of silver particles to modify the polarization of an
      incident, linearly polarized plane wave in a desired fashion while localizing the
      light in space. The results provide insight into the structural features that
      determine the birefringence properties of metal nanoparticles and their arrays.
      Of the variety of potential applications that may be envisioned, we note the
      design of nanoscale light sources with controllable coherence and polarization
      properties that could serve for coherent control of molecular, electronic, or
      electromechanical dynamics in the nanoscale.

PMID- 18715102
TI  - Charge transfer in the TCNQ-sexithiophene complex.
AB  - Molecular crystals from thiophene molecules can be doped with TCNQ-F4 molecules
      for use in all-organic optoelectronic and semiconductor devices. The charge
      transfer and the molecular orbital energy level formation in between these two
      organic molecules are investigated here by density functional theory
      calculations. The isolated molecules are calculated nonbonded and bonded
      together, forming a charge transfer complex (CTC). The relaxed structure of the
      complex shows essentially coplanar and centered molecules with the alpha
      sexithiophene rings tilted alternatingly by 4.8 degrees. The bond formation of
      these molecules results in a charge transfer of approximately 0.4 e from the
      alpha-sexithiophene to the TCNQ-F4 molecule. The highest occupied molecular
      orbital-lowest unoccupied molecular orbital gap width is reduced as compared to
      the isolated molecules due to the newly formed orbitals in the CTC. Upon
      adsorption on a Au(111) surface, electrons are transferred onto the molecule
      complex, thereby causing the molecular levels to align asymmetric with respect to
      the charge neutrality level. The theoretical results for the single molecule and
      CTC layer are compared to experimental photoemission and scanning tunneling
      spectroscopy results.

PMID- 18715103
TI  - Interactions between polymer brushes in solvents of variable quality: a density
      functional theory study.
AB  - We present a density functional theory study of interactions between sterically
      stabilized colloidal particles in solvents of variable quality. Both flat and
      spherical polymer brushes are considered, as well as both monatomic and polymeric
      solvents. It is shown that the interaction between sterically stabilized
      particles can be tuned from repulsive to attractive by varying the solvent
      quality, the relative length of free and grafted chains, and by employing a mixed
      brush consisting of both well and poorly solvated chains.

PMID- 18715104
TI  - Phase behaviors of polymer solutions using molecular simulation technique.
AB  - Phase behaviors of polymer solutions are estimated using a combination of
      thermodynamic models and molecular simulation technique. In general, many
      parameters of binary systems are determined by fitting a thermodynamic model with
      experimental data. In this study, we obtained all parameters using molecular
      simulation. To take the specific interaction into account, we assume that it only
      occurs between a solvent molecule and a specific group. Our results show that the
      theoretical treatment accounting for the specific interaction gives more accurate
      predictions than those without consideration of specific interaction. Also, our
      approach describes the phase equilibria of various polymer solutions over the
      entire concentration remarkably well.

PMID- 18715106
TI  - X-ray induced damage in DNA monitored by X-ray photoelectron spectroscopy.
AB  - In this work, the chemical changes in calf thymus DNA samples were analyzed by X
      ray photoelectron spectroscopy (XPS). The DNA samples were irradiated for over 5
      h and spectra were taken repeatedly every 30 min. In this approach the X-ray beam
      both damages and probes the samples. In most cases, XPS spectra have complex
      shapes due to contributions of C, N, and O atoms bonded at several different
      sites. We show that from a comparative analysis of the modification in XPS line
      shapes of the C 1s, O 1s, N 1s, and P 2p peaks, one can gain insight into a
      number of reaction pathways leading to radiation damage to DNA.

PMID- 18715105
TI  - Cytoskeleton mediated effective elastic properties of model red blood cell
      membranes.
AB  - The plasma membrane of human red blood cells consists of a lipid bilayer attached
      to a regular network of underlying cytoskeletal polymers. We model this system at
      a dynamic coarse-grained level, treating the bilayer as an elastic sheet and the
      cytoskeletal network as a series of phantom entropic springs. In contrast to
      prior simulation efforts, we explicitly account for dynamics of the cytoskeletal
      network, both via motion of the protein anchors that attach the cytoskeleton to
      the bilayer and through breaking and reconnection of individual cytoskeletal
      filaments. Simulation results are explained in the context of a simple mean field
      percolation model and comparison is made to experimental measurements of red
      blood cell fluctuation amplitudes.

PMID- 18715107
TI  - Folding transition of a single semiflexible polyelectrolyte chain through
      toroidal bundling of loop structures.
AB  - We consider how the DNA coil-globule transition progresses via the formation of a
      toroidal ring structure. We formulate a theoretical model of this transition as a
      phenomenon in which an unstable single loop generated as a result of thermal
      fluctuation is stabilized through association with other loops along a
      polyelectrolyte chain. An essential property of the chain under consideration is
      that it follows a wormlike chain model. A toroidal bundle of loop structures is
      characterized by a radius and a winding number. The statistical properties of
      such a chain are discussed in terms of the free energy as a function of the
      fraction of unfolded segments. We also present an actual experimental observation
      of the coil-globule transition of single giant DNA molecules, T4 DNA (165.5 kbp),
      with spermidine (3+), where intrachain phase segregation appears at a NaCl
      concentration of more than 10 mM. Both the theory and experiments lead to two
      important points. First, the transition from a partially folded state to a
      completely folded state has the characteristics of a continuous transition, while
      the transition from an unfolded state to a folded state has the characteristics
      of a first-order phase transition. Second, the appearance of a partially folded
      structure requires a folded structure to be less densely packed than in the fully
      folded compact state.

PMID- 18715108
TI  - Revisiting the real space density functional theory of hard sphere freezing in
      the Percus-Yevick approximation.

PMID- 18715109
TI  - Reaction coordinate in electron transfer: what physical quantity should we use
      for it?

PMID- 18715110
TI  - Comment on: "On the reality of residual entropies of glasses and disordered
      crystals" [J. Chem. Phys. 128, 154510 (2008)].

PMID- 18715113
TI  - Cancer screening: a mathematical model relating secreted blood biomarker levels
      to tumor sizes.
AB  - BACKGROUND: Increasing efforts and financial resources are being invested in
      early cancer detection research. Blood assays detecting tumor biomarkers promise
      noninvasive and financially reasonable screening for early cancer with high
      potential of positive impact on patients' survival and quality of life. For novel
      tumor biomarkers, the actual tumor detection limits are usually unknown and there
      have been no studies exploring the tumor burden detection limits of blood tumor
      biomarkers using mathematical models. Therefore, the purpose of this study was to
      develop a mathematical model relating blood biomarker levels to tumor burden.
      METHODS AND FINDINGS: Using a linear one-compartment model, the steady state
      between tumor biomarker secretion into and removal out of the intravascular space
      was calculated. Two conditions were assumed: (1) the compartment (plasma) is well
      mixed and kinetically homogenous; (2) the tumor biomarker consists of a protein
      that is secreted by tumor cells into the extracellular fluid compartment, and a
      certain percentage of the secreted protein enters the intravascular space at a
      continuous rate. The model was applied to two pathophysiologic conditions: tumor
      biomarker is secreted (1) exclusively by the tumor cells or (2) by both tumor
      cells and healthy normal cells. To test the model, a sensitivity analysis was
      performed assuming variable conditions of the model parameters. The model
      parameters were primed on the basis of literature data for two established and
      well-studied tumor biomarkers (CA125 and prostate-specific antigen [PSA]).
      Assuming biomarker secretion by tumor cells only and 10% of the secreted tumor
      biomarker reaching the plasma, the calculated minimally detectable tumor sizes
      ranged between 0.11 mm(3) and 3,610.14 mm(3) for CA125 and between 0.21 mm(3) and
      131.51 mm(3) for PSA. When biomarker secretion by healthy cells and tumor cells
      was assumed, the calculated tumor sizes leading to positive test results ranged
      between 116.7 mm(3) and 1.52 x 10(6) mm(3) for CA125 and between 27 mm(3) and
      3.45 x 10(5) mm(3) for PSA. One of the limitations of the study is the absence of
      quantitative data available in the literature on the secreted tumor biomarker
      amount per cancer cell in intact whole body animal tumor models or in cancer
      patients. Additionally, the fraction of secreted tumor biomarkers actually
      reaching the plasma is unknown. Therefore, we used data from published cell
      culture experiments to estimate tumor cell biomarker secretion rates and assumed
      a wide range of secretion rates to account for their potential changes due to
      field effects of the tumor environment. CONCLUSIONS: This study introduced a
      linear one-compartment mathematical model that allows estimation of minimal
      detectable tumor sizes based on blood tumor biomarker assays. Assuming
      physiological data on CA125 and PSA from the literature, the model predicted
      detection limits of tumors that were in qualitative agreement with the actual
      clinical performance of both biomarkers. The model may be helpful in future
      estimation of minimal detectable tumor sizes for novel proteomic biomarker assays
      if sufficient physiologic data for the biomarker are available. The model may
      address the potential and limitations of tumor biomarkers, help prioritize
      biomarkers, and guide investments into early cancer detection research efforts.

PMID- 18715115
TI  - Ensuring the involvement of children in the evaluation of new tuberculosis
      treatment regimens.

PMID- 18715114
TI  - Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in
      microglia/macrophage activation.
AB  - BACKGROUND: Chondroitin sulfate proteoglycan (CSPG) is a major component of the
      glial scar. It is considered to be a major obstacle for central nervous system
      (CNS) recovery after injury, especially in light of its well-known activity in
      limiting axonal growth. Therefore, its degradation has become a key therapeutic
      goal in the field of CNS regeneration. Yet, the abundant de novo synthesis of
      CSPG in response to CNS injury is puzzling. This apparent dichotomy led us to
      hypothesize that CSPG plays a beneficial role in the repair process, which might
      have been previously overlooked because of nonoptimal regulation of its levels.
      This hypothesis is tested in the present study. METHODS AND FINDINGS: We
      inflicted spinal cord injury in adult mice and examined the effects of CSPG on
      the recovery process. We used xyloside to inhibit CSPG formation at different
      time points after the injury and analyzed the phenotype acquired by the
      microglia/macrophages in the lesion site. To distinguish between the resident
      microglia and infiltrating monocytes, we used chimeric mice whose bone marrow
      derived myeloid cells expressed GFP. We found that CSPG plays a key role during
      the acute recovery stage after spinal cord injury in mice. Inhibition of CSPG
      synthesis immediately after injury impaired functional motor recovery and
      increased tissue loss. Using the chimeric mice we found that the immediate
      inhibition of CSPG production caused a dramatic effect on the spatial
      organization of the infiltrating myeloid cells around the lesion site, decreased
      insulin-like growth factor 1 (IGF-1) production by microglia/macrophages, and
      increased tumor necrosis factor alpha (TNF-alpha) levels. In contrast, delayed
      inhibition, allowing CSPG synthesis during the first 2 d following injury, with
      subsequent inhibition, improved recovery. Using in vitro studies, we showed that
      CSPG directly activated microglia/macrophages via the CD44 receptor and modulated
      neurotrophic factor secretion by these cells. CONCLUSIONS: Our results show that
      CSPG plays a pivotal role in the repair of injured spinal cord and in the
      recovery of motor function during the acute phase after the injury; CSPG
      spatially and temporally controls activity of infiltrating blood-borne monocytes
      and resident microglia. The distinction made in this study between the beneficial
      role of CSPG during the acute stage and its deleterious effect at later stages
      emphasizes the need to retain the endogenous potential of this molecule in repair
      by controlling its levels at different stages of post-injury repair.

PMID- 18715116
TI  - The thief in the mirror.

PMID- 18715117
TI  - Mirror-induced behavior in the magpie (Pica pica): evidence of self-recognition.
AB  - Comparative studies suggest that at least some bird species have evolved mental
      skills similar to those found in humans and apes. This is indicated by feats such
      as tool use, episodic-like memory, and the ability to use one's own experience in
      predicting the behavior of conspecifics. It is, however, not yet clear whether
      these skills are accompanied by an understanding of the self. In apes, self
      directed behavior in response to a mirror has been taken as evidence of self
      recognition. We investigated mirror-induced behavior in the magpie, a songbird
      species from the crow family. As in apes, some individuals behaved in front of
      the mirror as if they were testing behavioral contingencies. When provided with a
      mark, magpies showed spontaneous mark-directed behavior. Our findings provide the
      first evidence of mirror self-recognition in a non-mammalian species. They
      suggest that essential components of human self-recognition have evolved
      independently in different vertebrate classes with a separate evolutionary
      history.

PMID- 18715118
TI  - The NDR/LATS family kinase Cbk1 directly controls transcriptional asymmetry.
AB  - Cell fate can be determined by asymmetric segregation of gene expression
      regulators. In the budding yeast Saccharomyces cerevisiae, the transcription
      factor Ace2 accumulates specifically in the daughter cell nucleus, where it
      drives transcription of genes that are not expressed in the mother cell. The
      NDR/LATS family protein kinase Cbk1 is required for Ace2 segregation and
      function. Using peptide scanning arrays, we determined Cbk1's phosphorylation
      consensus motif, the first such unbiased approach for an enzyme of this family,
      showing that it is a basophilic kinase with an unusual preference for histidine 
      5 to the phosphorylation site. We found that Cbk1 phosphorylates such sites in
      Ace2, and that these modifications are critical for Ace2's partitioning and
      function. Using proteins marked with GFP variants, we found that Ace2 moves from
      isotropic distribution to the daughter cell nuclear localization, well before
      cytokinesis, and that the nucleus must enter the daughter cell for Ace2
      accumulation to occur. We found that Cbk1, unlike Ace2, is restricted to the
      daughter cell. Using both in vivo and in vitro assays, we found that two critical
      Cbk1 phosphorylations block Ace2's interaction with nuclear export machinery,
      while a third distal modification most likely acts to increase the transcription
      factor's activity. Our findings show that Cbk1 directly controls Ace2, regulating
      the transcription factor's activity and interaction with nuclear export machinery
      through three phosphorylation sites. Furthermore, Cbk1 exhibits a novel
      specificity that is likely conserved among related kinases from yeast to
      metazoans. Cbk1 is functionally restricted to the daughter cell, and cannot
      diffuse from the daughter to the mother. In addition to providing a mechanism for
      Ace2 segregation, these findings show that an isotropically distributed cell fate
      determinant can be asymmetrically partitioned in cytoplasmically contiguous cells
      through spatial segregation of a regulating protein kinase.

PMID- 18715119
TI  - Direct estimation of the mitochondrial DNA mutation rate in Drosophila
      melanogaster.
AB  - Mitochondrial DNA (mtDNA) variants are widely used in evolutionary genetics as
      markers for population history and to estimate divergence times among taxa.
      Inferences of species history are generally based on phylogenetic comparisons,
      which assume that molecular evolution is clock-like. Between-species comparisons
      have also been used to estimate the mutation rate, using sites that are thought
      to evolve neutrally. We directly estimated the mtDNA mutation rate by scanning
      the mitochondrial genome of Drosophila melanogaster lines that had undergone
      approximately 200 generations of spontaneous mutation accumulation (MA). We
      detected a total of 28 point mutations and eight insertion-deletion (indel)
      mutations, yielding an estimate for the single-nucleotide mutation rate of 6.2 x
      10(-8) per site per fly generation. Most mutations were heteroplasmic within a
      line, and their frequency distribution suggests that the effective number of
      mitochondrial genomes transmitted per female per generation is about 30. We
      observed repeated occurrences of some indel mutations, suggesting that indel
      mutational hotspots are common. Among the point mutations, there is a large
      excess of G-->A mutations on the major strand (the sense strand for the majority
      of mitochondrial genes). These mutations tend to occur at nonsynonymous sites of
      protein-coding genes, and they are expected to be deleterious, so do not become
      fixed between species. The overall mtDNA mutation rate per base pair per fly
      generation in Drosophila is estimated to be about 10x higher than the nuclear
      mutation rate, but the mitochondrial major strand G-->A mutation rate is about
      70x higher than the nuclear rate. Silent sites are substantially more strongly
      biased towards A and T than nonsynonymous sites, consistent with the extreme
      mutation bias towards A+T. Strand-asymmetric mutation bias, coupled with
      selection to maintain specific nonsynonymous bases, therefore provides an
      explanation for the extreme base composition of the mitochondrial genome of
      Drosophila.

PMID- 18715120
TI  - Intrapulmonary and intracardiac shunting with exercise at altitude.
AB  - Recent studies in normal participants have shown that right to left shunt blood
      vessels in the lung open up during exercise. We describe the first field study to
      investigate this phenomenon at altitude. This study aimed to assess the effect of
      altitude and partial acclimatization on inducible right to left shunting at rest
      and with exercise. A contrast-enhanced transcranial Doppler imaging technique to
      detect microbubbles after injection of blood and saline agitated with air was
      used to measure right to left shunting in 10 normal participants at rest and
      immediately after exercising to maximum oxygen consumption (VO(2max)) at 80 m, on
      acute exposure to 3450 m, and finally after a week above 3450 m. At 80 m,
      exercising resulted in right to left shunting via patent foramen ovale in 2
      participants, but there was no evidence of shunting in the remaining 8
      participants. Cerebral microbubbles were detected at rest in the 2 participants
      with patent foramen ovale on acute exposure to 3450 m, and the shunting increased
      on exercise (P = .04). In 5 of the remaining 8 participants without patent
      foramen ovale, cerebral microbubbles were detected on exercise (P = .04) but not
      at rest. Partial acclimatization had minimal effect on the prevalence or
      magnitude of the intrapulmonary or intracardiac shunts. Oxygenation was similar
      in those with shunts compared with those without shunts. Intrapulmonary shunting
      occurs on exercise at altitude, but the clinical and physiologic significances
      have yet to be determined. Despite the occurrence of shunting in most
      participants, our results suggest that this phenomenon is not a significant
      factor in altitude and exercise-induced hypoxia.

PMID- 18715121
TI  - Snakes of medical significance in India: the first reported case of envenoming by
      the Levantine viper (Macrovipera lebetina).
AB  - This article reports for the first time the medical significance of the Levantine
      viper (Macrovipera lebetina) in India. This snake is found in India in the
      mountainous regions of Jammu and Kashmir and is capable of causing necrosis and
      hemostatic manifestations, as seen in the case reported here. It is thus a class
      II snake of medical significance, as defined by the World Health Organization
      grading scale. This finding reinforces the recent decision by the Indian
      Government to abandon the term "Big Four" to describe important venomous species
      in India. Levantine viper venom is not included in the manufacture of Indian
      polyvalent anti-snake venom; thus, there is no current antidote for this species.
      Recommendations are to manage confirmed bites from this species without Indian
      anti-snake venom. In areas where this snake is found to be a significant
      contributor to envenomations, alternative anti-snake venoms can be sourced from
      outside India for use in high-risk groups. Continuing attention to preserving
      dead snakes brought with the victim for reliable identification remains a high
      priority.

PMID- 18715122
TI  - Mental health issues on expedition.

PMID- 18715123
TI  - Inducing hypoxemia in healthy humans: a method for intermittently lowering
      arterial blood oxygenation during physiological studies.

PMID- 18715124
TI  - Is high-altitude environment a risk factor for childhood overweight and obesity
      in Saudi Arabia?
AB  - OBJECTIVE: To describe the prevalence of childhood overweight and obesity in
      rural high- and low-altitude populations of southwestern Saudi Arabia and to
      identify specific at-risk groups within these populations. METHODS: A cross
      sectional study was conducted on 912 school children and adolescents aged 6-15
      years born and living permanently at high altitudes (2800-3150 m) and 972
      children and adolescents of comparable ages born and living permanently at low
      altitudes (< or =500 m). Height and weight were measured. For children <10 years,
      the weight-to-height index according to World Health Organization (WHO) standards
      was used for assessing overweight and obesity. For adolescents 10-15 years,
      overweight and obesity were assessed by age and gender-specific percentiles for
      body mass index based on the WHO/National Centre for Health Statistics reference
      population. A questionnaire was used for measuring parents' socioeconomic status.
      RESULTS: The overall prevalence of overweight and obesity at high and low
      altitudes was 10%. The study showed that some school children and adolescents
      were at a significantly higher risk of developing overweight and obesity.
      Significant risk factors included moderate-to-high parental income, age > or =10
      years, high-altitude birth and residence, and female sex (crude odds ratio 3.2
      [95% CI, 1.8- 5.5], 2.3 [95% CI, 1.6-3.2], 2.1 [95% CI, 1.5-2.9], and 1.9 [95%
      CI, 1.4-2.6], respectively). A multivariate analysis using the direct binary
      logistic regression model revealed that moderate-to-high parental income, age >
      or =10 years, female sex, and high-altitude birth and residence were significant
      independent predictors of childhood overweight and obesity. (adjusted OR 3.2 [95%
      CI, 1.6-2.6], 2.6 [95% CI, 1.8-3.8], 2.0 [95% CI, 1.6-2.9], and 1.8 [95% CI, 1.3
      2.6]), respectively. CONCLUSION: The present study identified risk factors for
      childhood overweight and obesity in Saudi Arabia. Among these, high altitude was
      a significant and independent factor. Future research is warranted to evaluate
      the exact mechanism by which a high-altitude environment may contribute to
      childhood overweight and obesity.

PMID- 18715125
TI  - Effects of an electrolyte additive on hydration and drinking behavior during
      wildfire suppression.
AB  - OBJECTIVE: The purpose of this study was to compare the effects of a water +
      electrolyte solution versus plain water on changes in drinking behaviors,
      hydration status, and body temperatures during wildfire suppression. METHODS:
      Eight participants consumed plain water, and eight participants consumed water
      plus an electrolyte additive during 15 hours of wildfire suppression.
      Participants wore a specially outfitted backpack hydration system equipped with a
      digital flow meter system affixed inline to measure drinking characteristics
      (drinking frequency and volume). Body weight and urine-specific gravity were
      collected pre- and postshift. Ambient, core, and skin temperatures were measured
      continuously using a wireless system. Work output was monitored using
      accelerometry. RESULTS: There were no differences between groups for body weight,
      drinking frequency, temperature data, activity, or urine-specific gravity (1.019
      +/- 0.007 to 1.023 +/- 0.010 vs. 1.019 +/- 0.005 to 1.024 +/- 0.009 for water and
      water + electrolyte groups pre- and postshift, respectively; P < .05). There was
      a main effect for time for body weight, demonstrating an overall decrease (78.1
      +/- 13.3 and 77.3 +/- 13.3 kg pre- and postshift, respectively; P < .05) across
      the work shift. The water group consumed more total fluid (main effect for
      treatment) than the water + electrolyte group (504 +/- 472 vs. 285 +/- 279 mL.h(
      1) for the water and water + electrolyte groups, respectively; P < .05).
      CONCLUSION: The addition of an electrolyte mixture to plain water decreased the
      overall fluid consumption of the water + electrolyte group by 220 mL.h(-1) (3.3
      L.d(-1)). Supplementing water with electrolytes can reduce the amount of fluid
      necessary to consume and transport during extended activity. This can minimize
      carrying excessive weight, possibly reducing fatigue during extended exercise.

PMID- 18715126
TI  - Maximum exercise responses of men and women mountaineering trainees on induction
      to high altitude (4350 m) by trekking.
AB  - OBJECTIVE: Maximum aerobic capacity decreases at high altitude. This study was
      conducted to compare the changes in maximum aerobic capacity in men and women
      mountaineering trainees on induction to high altitude at 4350 m by trekking.
      METHODS: Eight men and 8 women mountaineering trainees in a mountaineering course
      were selected for the study. The initial study was conducted at 2100 m (586 mm
      Hg) and then during 6 to 7 days of sojourn at 4350 m (435 mm Hg). Maximum oxygen
      consumption (VO(2max)), maximum heart rate (HR(max)), pulse arterial oxygen
      saturation (SaO(2)), and maximum ventilation (VE(max)) were measured. RESULTS:
      VO(2max), HR(max), duration of work (minutes), and SaO(2) saturation decreased
      significantly (P < .05) with increasing altitude in both sexes. Conversely,
      VE(max) and ventilatory equivalent (VE/VO(2)) increased significantly (P < .05).
      Men showed a relatively higher value of maximum exercise variables (total
      exercise time, exercise intensity, and VO(2)) than women trainees at both
      altitude locations. The decrement of VO(2max) was 13% in women and 17% in men (P
      < .05). CONCLUSIONS: The results indicate that the decrement of maximum aerobic
      capacity at 4350 m was less in women than in men under similar modes of ascent.

PMID- 18715127
TI  - Students experience self-esteem improvement during mountaineering.
AB  - INTRODUCTION: Despite ample evidence in the literature of the correlation between
      sports participation in general and self-esteem, there is a dearth of information
      regarding the probable impact of specific sporting activities on self-concept.
      We, therefore, sought to assess the effect of mountaineering on self-esteem and
      its correlates in university students. METHODS: This longitudinal study recruited
      54 students (male 26%, female 74%) from different universities in the capital
      city of Iran, Tehran. The students participated in a mountaineering program in
      Mt. Damavand in July 2006. The Rosenberg Self-Esteem Scale (RSES), SF-36, and
      Hospital Anxiety and Depression Scale (HADS) were completed by all the
      participants before and after this activity. Their demographic data and
      mountaineering experience were also collected. RESULTS: Mean RSES after climbing
      was significantly higher than before the experience (24.78 +/- 2.4 vs. 23.67 +/-
      3.3; P = .002). Self-esteem was correlated with bodily pain, and its improvement
      was correlated with mental health and depression (P < .05). Self-esteem and its
      improvement were not significantly correlated with age, sex, marital status,
      prior personal and family history of mountaineering, past history of mountain
      sickness, and reaching the summit (P > .05). CONCLUSION: This study showed that
      participation in a single mountaineering program improved students' sense of self
      esteem. We suggest that taking up this activity might have benefits for students
      with depression.

PMID- 18715128
TI  - Search and rescue trends and the emergency medical service workload in Utah's
      National Parks.
AB  - OBJECTIVE: To identify the emergency medical service (EMS) workload and trends
      associated with search and rescue (SAR) operations in Utah's National Park
      Service (NPS) units. METHODS: Data for this study were collected from the Annual
      Emergency Medical Services Report and the Annual Search and Rescue Report for
      National Park Service units in Utah from 2001-2005. RESULTS: There were 4762 EMS
      incidents reported between 2001 and 2005, including 79 fatalities (50 traumatic;
      29 nontraumatic). The most common EMS transportation method was ground (1505) and
      helicopter (553) transport. The heaviest trauma, medical, and cardiac workload
      was at Glen Canyon National Recreation Area (GLCA) and the heaviest first aid
      workload was at Zion National Park (ZION). There were 1190 SAR operations between
      2001 and 2005 involving 67 fatalities, 623 ill or injured visitors, 1813 non-ill
      or non-injured visitors, and 92 saves. GLCA and ZION accounted for 47% and 21% of
      all SAR operations. The total cost of SAR operations was $1 363 920. SAR
      operations most commonly occurred on weekends, involved male visitors (59%),
      visitors aged 20-29 years (23%), and 40-49 years (20%), and visitors
      participating in day hiking (221), motorized boating (196), and canyoneering (98)
      activities. Most SAR operations were in lake (226), desert (147), and canyon
      (140) environments and were resolved within 24 hours. CONCLUSIONS: GLCA and ZION
      experienced heavy use of EMS resources that should be noted by EMS administrators
      and planners. GLCA and ZION also reported the most SAR operations. The
      development of techniques to prevent the need for SAR at GLCA and ZION would
      likely have the most potential to reduce the financial impact of SAR incidents
      and morbidity and mortality to visitors.

PMID- 18715129
TI  - Trekking and climbing in the Solukhumbu district of Nepal: impact on
      socioeconomic status and health of lowland porters.

PMID- 18715130
TI  - Introduction to 'Wilderness medicine education in the city: a new paradigm'.

PMID- 18715131
TI  - Time for an alternative perspective: the eternal problem of supply and quality of
      anti snake venom in the developing world--"it's the economy, stupid".
AB  - The "crisis in anti snake venom supply" has been an enduring problem. Despite the
      frequency with which it appears in the literature, it remains unquantified and an
      enigma. If there is a serious shortage of anti snake venom (ASV), why has this
      not been resolved? Anti snake venoms are produced, and yet many suppliers are
      described as leaving the market. There appears to be a problem in the call for
      highly effective, high-quality, and cheap anti venoms that contributes to this
      result of suppliers leaving the market. Private companies are tasked with
      achieving adequate shareholder returns and by doing so ensure continued supply.
      Efforts should therefore target a means of lowering production cost by
      introducing whole immunoglobulin G (IgG) antivenoms with greater antibody yields,
      reducing the drive to eliminate adverse reactions, for which there are other more
      cost-effective treatments, as well as a means of introducing good manufacturing
      processes, with care based on demonstrable need. In order to ensure
      sustainability of supply, a private company supplier providing a whole IgG
      antivenom that effectively neutralizes venom is the most credible option. The
      need for ASV in areas of shortage mandates the need for clear decisions regarding
      the type of ASV and the recognition that the market requires acceptable returns
      for producers if supply is to be sustainable. This paper reviews the economic
      realities of ASV production and suggests a pragmatic, sustainable approach to the
      problem of supplying ASV to developing countries.

PMID- 18715132
TI  - Fatal craniocerebral injury from wild boar attack.

PMID- 18715133
TI  - Wilderness medicine in academic medical education.

PMID- 18715134
TI  - Wilderness medicine education in the city: a new paradigm.

PMID- 18715135
TI  - Mechanical stimulation of mesenchymal stem cell proliferation and differentiation
      promotes osteogenesis while preventing dietary-induced obesity.
AB  - Mesenchymal stem cells (MSCs) are defined by their ability to self-renew and
      differentiate into the cells that form mesodermal tissues such as bone and fat.
      Low magnitude mechanical signals (LMMS) have been shown to be anabolic to bone
      and have been recently reported to suppress the development of fat in normal
      animals fed a regular diet. Using male C57BL/6J mice, the ability of LMMS (0.2g,
      90-Hz signal applied for 15 min/d, 5 d/wk) to simultaneously promote bone
      formation and prevent diet-induced obesity was correlated to mechanical
      influences on the molecular environment of the bone marrow, as indicated by the
      population dynamics and lineage commitment of MSCs. Six weeks of LMMS increased
      the overall marrow-based stem cell population by 37% and the number of MSCs by
      46%. Concomitant with the increase in stem cell number, the differentiation
      potential of MSCs in the bone marrow was biased toward osteoblastic and against
      adipogenic differentiation, as reflected by upregulation of the transcription
      factor Runx2 by 72% and downregulation of PPARgamma by 27%. The phenotypic impact
      of LMMS on MSC lineage determination was evident at 14 wk, where visceral adipose
      tissue formation was suppressed by 28%, whereas trabecular bone volume fraction
      in the tibia was increased by 11%. Translating this to the clinic, a 1-yr trial
      in young women (15-20 yr; n = 48) with osteopenia showed that LMMS increased
      trabecular bone in the spine and kept visceral fat at baseline levels, whereas
      control subjects showed no change in BMD, yet an increase in visceral fat.
      Mechanical modulation of stem cell proliferation and differentiation indicates a
      unique therapeutic target to aid in tissue regeneration and repair and may
      represent the basis of a nonpharmacologic strategy to simultaneously prevent
      obesity and osteoporosis.

PMID- 18715136
TI  - Bisphosphonate therapy ameliorates hearing loss in mice lacking osteoprotegerin.
AB  - Three auditory ossicles including the malleus, incus, and stapes conduct sound in
      the middle ear from the tympanic membrane to the inner ear. Auditory ossicles are
      massively resorbed by osteoclasts in Opg(-/-) mice, which lack osteoprotegerin
      (OPG), a soluble decoy receptor for the osteoclastogenic cytokine RANKL. Opg(-/-)
      mice exhibit progressive hearing loss and are a model for juvenile Paget's
      disease. However, effects of antiresorptive treatment on auditory ossicles and on
      hearing function in Opg(-/-) mice are unknown. We intraperitoneally injected Opg(
      /-) mice with bisphosphonate risedronate 5 d/wk for 9 wk. Morphology of auditory
      ossicles was examined microscopically, radiographically, and histologically.
      Hearing function was monitored by measuring the auditory brain stem response
      (ABR). Control Opg(-/-) mice exhibited thinning of all three ossicles and tibia.
      In contrast, risedronate treatment significantly inhibited bone loss in auditory
      ossicles as well as in long bones of Opg(-/-) mice. Bony fusion of the junction
      between the stapes and the otic capsule was reduced after treatment. Moreover,
      ABR measurement showed that hearing in Opg(-/-) mice was significantly improved
      by risedronate treatment. These data suggest that hearing loss in pathologies
      characterized by excessive resorption of the auditory ossicles may be prevented
      by bisphosphonates.

PMID- 18715138
TI  - Diaminobutane (DAB) dendrimers are potent binders of oral phosphate.
AB  - Reduction of blood phosphorus is a critical component in the management of
      secondary hyperparathyroidism in chronic kidney disease patients. In addition to
      dialysis treatment and dietary phosphorus restriction, oral phosphate binders are
      often consumed with meals to reduce the availability of food phosphorus. Several
      oral phosphate binders are approved for use in chronic kidney disease patients,
      but all have practical limitations because of toxicity, poor efficacy, or high
      cost. Using an in vivo method to measure intestinal phosphate absorption in rats
      using radiolabeled phosphate, we found that first-, second-, third-, and fifth
      generation diaminobutane dendrimer compounds, DAB-4-Cl, DAB-8-Cl, DAB-16-Cl, and
      DAB-64-Cl, respectively, drastically reduce the absorption of inorganic phosphate
      in a dose-dependent manner. To avoid complications of metabolic acidosis caused
      by hydrochloride salts, an acetate salt, DAB-9-AcOH, was prepared and shown to be
      equally effective at binding radiolabeled phosphate as DAB-8-Cl. DAB-8-AcOH was
      further shown to increase fecal phosphorus and decrease serum phosphorus in a
      dose-dependent manner when fed to rats. These data suggest that dendrimer
      compounds are of great potential use in the binding of food phosphate for the
      management of hyperparathyroidism secondary to chronic kidney disease.

PMID- 18715137
TI  - Successful skeletal aging: a marker of low fracture risk and longevity. The Study
      of Osteoporotic Fractures (SOF).
AB  - Successful aging is multidimensional, and many phenotypes have been proposed. We
      examined a biomarker of aging based on repeated measures of BMD for up to 15 yr
      and hypothesized that maintenance of BMD will be associated with low fracture
      risk and disability and improved survival. We studied 9704 women recruited at
      four U.S. clinical centers and enrolled in the Study of Osteoporotic Fractures, a
      longitudinal cohort study. Of these, 8224 women had at least one hip BMD
      measurement. Hip BMD was measured a maximum of five times over 15 yr. Random
      effects regression was used to determine a BMD slope for each subject. Three
      groups were formed-"maintained" BMD: slope >or=0, n = 724 (9%); "expected" BMD
      loss: slope <0 to <1 SD below mean, n = 6478 (79%); and "accelerated" BMD loss:
      slope >or=1 SD below mean, n = 1022 (12%). Cox proportional hazards models were
      used to compare the relative hazard (RH; 95% CI) of fracture, incident mobility
      disability, and mortality in the maintained and accelerated groups compared with
      the expected. A 1 SD decrease in the BMD slope was associated with an increased
      risk of all outcomes. In multivariate models, the RH of nonspine fracture was
      0.81 (0.71-0.93) and of hip fracture was 0.36 (0.25-0.53) for women in the
      maintained compared with the expected group. The incidence of mobility disability
      was lower in the maintained versus expected group (RH = 0.70; 95% CI = 0.59
      0.83), but this was largely explained by other factors. Women who experienced
      accelerated bone loss were more likely to develop disability (RH = 1.56; 95% CI:
      1.33-1.84). Mortality risks were lower in the maintained compared with the
      expected group (RH = 0.49; 95% CI: 0.42-0.58). In conclusion, a subset of older
      women maintained their BMD up to 15 yr, suggesting that bone loss is not an
      inevitable consequence of aging. These women experienced a lower risk of
      fractures, disability, and mortality, suggesting that this phenotype may be a
      marker of successful aging.

PMID- 18715139
TI  - Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with
      spinal BMD in 9-year-old children.
AB  - The C677T MTHFR polymorphism has been associated with lumbar spine and hip BMD.
      In older adults, the genetic effect has been reported in women only. However, in
      younger adults, this influence may only be present in men. This study is the
      first to investigate associations between the C677T MTHFR polymorphism and bone
      phenotypes in children. Regression analyses were used to study the relationship
      between MTHFR genotype and bone phenotypes derived from total body DXA scans in
      children 9.9 yr of age from the Avon Longitudinal Study of Parents and Children
      (ALSPAC). A total of 5816 children had both genetic and DXA data for the total
      body less head region (TBLH) and 3196 for the spine. A strong association was
      observed between the C677T MTHFR genotype and spine BMD (p < 0.001; 0.10 SD
      decrease per T allele). There was some evidence that this genetic effect was
      stronger in boys compared with girls (p = 0.04 for sex interaction). In contrast,
      there was no association between the C677T MTHFR genotype and TBLH BMD. The
      association between MTHFR genotype and spine BMD was attenuated particularly in
      girls by high maternal dietary intakes of vitamin B(6) and folate during
      pregnancy but not by child dietary intakes at 7 yr. To the extent that these
      findings reflect known influences of C677T MTHFR genotype on plasma homocysteine
      levels, our results suggest that the latter is an important regulator of spinal
      BMD in childhood.

PMID- 18715140
TI  - Functional characterization of genetic variation in the Frizzled 1 (FZD1)
      promoter and association with bone phenotypes: more to the LRP5 story?
AB  - WNT signaling is an important determinant of bone formation. The WNT co-receptor,
      Frizzled homolog 1 (FZD1), initiates WNT signal transduction. To study the
      influence of FZD1 genetic variation on measures of bone health, we first
      sequenced a 6.8-kb region surrounding FZD1 in 48 samples of African ancestry. We
      genotyped all common polymorphisms and performed association analysis with bone
      phenotypes in a larger sample. Only 3 of 35 SNPs identified were present in
      >or=5% of the sample and assayed further in 1084 men of African ancestry. Two of
      these SNPs were in the FZD1 promoter (rs2232157, rs2232158) and were associated
      with femoral neck areal BMD (p = 0.041 and 0.009, respectively). The minor
      alleles of these two SNPs were also associated with larger bone size at the
      radius (p < 0.05 for both), and rs2232158 was associated with greater strength
      strain index, an indicator of bone's ability to withstand torsion. Functional
      experiments were completed to assess the influence of the rs2232158 promoter
      polymorphism on transcriptional regulation of FZD1. The minor C allele in
      rs2232158 creates a binding site for the transcription factor Egr1, has higher
      Egr1 binding affinity, and has greater FZD1 promoter activity in MG63 and SaOS-2
      cells, providing a plausible molecular mechanism for the population associations.
      This study indicates that a cis-regulatory polymorphism in the FZD1 promoter
      region may have a functional role in determining bone structural geometry.

PMID- 18715141
TI  - Characterization of a novel Alu-Alu recombination-mediated genomic deletion in
      the TCIRG1 gene in five osteopetrotic patients.
AB  - Human malignant autosomal recessive osteopetrosis (ARO) is a genetically
      heterogeneous disorder caused by reduced bone resorption by osteoclasts.
      Biallelic mutations in the TCIRG1 gene, encoding the a3 subunit of the vacuolar
      proton pump, are responsible for more than one half of ARO patients. However, a
      few patients with monoallelic mutations have been described, raising the
      possibility of a dominant-like TCIRG1-dependent osteopetrosis, of a digenic
      disease, or of peculiar mutations difficult to detect with standard methods. We
      describe here a novel genomic deletion in the TCIRG1 gene explaining why, in some
      patients, mutations in only one allele have previously been found. The analysis
      of a proband from a consanguineous Turkish family allowed us to define the
      deletion boundaries encompassing introns 10 and 13 and occurring within AluSx
      repeat sequences, suggesting Alu-mediated homologous recombination as a
      mechanism. An identical genomic deletion at the heterozygous level was found in
      four unrelated Italian families in whom only a single mutated allele has
      previously been found. TCIRG1 haplotype analysis in these five families suggests
      a possible common ancestral origin for this large deletion. In summary, we
      describe the identification of a novel genomic deletion in the TCIRG1 gene that
      is of clinical relevance, especially in prenatal diagnosis.

PMID- 18715142
TI  - APE1/Ref-1: versatility in progress.
AB  - Apurinic/apyrimidinic endonuclease1/redox factor-1 (APE1/Ref-1) is a
      multifunctional protein involved in base excision DNA repair and in
      transcriptional regulation of gene expression. Over the past decade and a half,
      knowledge of the biological functions, interactions, mechanisms of action, and
      regulation of the protein APE1/Ref-1 has grown exponentially. The multifunctional
      nature of APE1/Ref-1 is uncovering and has been extensively studied in the
      cellular response against oxidative stress. Recent evidence shows a biological
      role of APE1/Ref-1 can be modulated by the different post-translational
      modification. Because of APE1/Ref-1 importance to genomic stability and cell
      survival, APE1/Ref-1 is focused as the leading therapeutic target molecule for
      the oxidative stress condition or pathologic conditions such as cancer. This
      forum, dedicated to APE1/Ref-1, provides ample testimony that even though we have
      learned a great deal about APE1/Ref-1 over the past 15-plus years, our knowledge
      still constitutes the tip of the iceberg when it comes to understanding this
      versatile protein.

PMID- 18715145
TI  - A dual regulatory role of apurinic/apyrimidinic endonuclease 1/redox factor-1 in
      HMGB1-induced inflammatory responses.
AB  - Apurinic/apyrimidinic endonuclease 1/Redox factor-1 (APE1) is a multifunctional
      protein involved in reduction-oxidation regulation. High-mobility group box 1
      (HMGB1) is released by necrotic cells and various inflammatory stimuli, acting as
      an inflammatory marker in sepsis and autoimmune diseases. Here, we report the
      dual regulatory role of APE1 in inflammatory signaling to extracellular HMGB1 or
      in the release of endogenous HMGB1 in human monocytes/macrophages. Forced
      cytoplasmic overexpression of APE1 profoundly attenuated the upregulation of
      HMGB1-mediated reactive oxygen species generation, cytokine secretion, and
      cyclooxygenase-2 expression by primary monocytes and macrophage-like THP-1 cell
      lines. In addition, HMGB1-induced activation of p38 and c-Jun N-terminal kinase
      (JNK), but not extracellular signal-regulated kinase 1/2, was strongly abrogated
      by the overexpression of APE1. The activation of apoptosis signal-regulating
      kinase 1 was required for both the p38 and JNK activation challenge with HMGB1.
      The extracellular release of HMGB1 by activated macrophages was inhibited by APE1
      transfection. Small interfering RNA (siRNA) knockdown of endogenous APE1 impaired
      HMGB1-mediated cytokine expression and MAPK activation in THP-1 cells. HMGB1
      stimulation induced the translocation of APE1 to the nucleus of the cell. In
      addition, APE1 silencing via siRNA transfection inhibited both the nuclear and
      cytoplasmic expression of APE1. These data identify APE1 as a novel dual
      regulator of inflammatory signaling to HMGB1 by human monocytes/macrophages. The
      modulation of cytosolic APE1 expression might be useful as a potential
      therapeutic modality for the treatment of inflammatory or autoimmune diseases.

PMID- 18715146
TI  - Parkinson-linked genes and toxins that affect neuronal cell death through the Bcl
      2 family.
AB  - Parkinson's disease (PD) results from the death of specific neuronal populations
      in the CNS. Potential causative factors include environmental toxins and gene
      mutations that can combine to dysregulate the processing and degradation of alpha
      synuclein. Oxidative stress induced by the neurotoxins MPTP, paraquat, maneb, and
      rotenone causes lipid peroxidation and protein misfolding that affects cell death
      through members of the Bcl-2 family. Sufficient activation of Bax and Bak
      facilitates mitochondrial outer-membrane permeabilization, which releases death
      inducing factors that cause apoptotic and nonapoptotic programmed cell death. The
      formation of alpha-synuclein aggregates is a defining pathologic feature of PD
      and is induced by these neurotoxins as well as several Parkinson-linked familial
      mutations. Of the familial mutations identified thus far, two of the loci encode
      proteins associated with ubiquitin-proteasome degradation of misfolded proteins
      (Parkin and Uch-L1), and two encode proteins associated with mitochondria and
      oxidative stress (DJ-1 and PINK1). Both gene and toxin findings indicate that
      dopaminergic neuron losses in PD are the result of oxidative stress affecting
      mitochondria function and ubiquitin-proteasome activity. Here we describe how
      related cell death mechanisms are involved in the pathophysiology of Parkinson's
      disease.

PMID- 18715144
TI  - Transcriptional regulatory functions of mammalian AP-endonuclease (APE1/Ref-1),
      an essential multifunctional protein.
AB  - The mammalian AP-endonuclease (APE1/Ref-1) plays a central role in the repair of
      oxidized and alkylated bases in mammalian genomes via the base excision repair
      (BER) pathway. However, APE1, unlike its E. coli prototype Xth, has two unique
      and apparently distinct transcriptional regulatory activities. APE1 functions as
      a redox effector factor (Ref-1) for several transcription factors including AP-1,
      HIF1-alpha, and p53. APE1 was also identified as a direct trans-acting factor for
      repressing human parathyroid hormone (PTH) and renin genes by binding to the
      negative calcium-response element (nCaRE) in their promoters. We have
      characterized APE1's post-translational modification, namely, acetylation which
      modulates its transcriptional regulatory function. Furthermore, stable
      interaction of APE1 with several other trans-acting factors including HIF-1alpha,
      STAT3, YB-1, HDAC1, and CBP/p300 and formation of distinct trans-acting complexes
      support APE1's direct regulatory function for diverse genes. Multiple functions
      of mammalian APE1, both in DNA repair and gene regulation, warrant extensive
      analysis of its own regulation and dissection of the mechanisms. In this review,
      we have discussed APE1's own regulation and its role as a transcriptional
      coactivator or corepressor by both redox-dependent and redox-independent
      (acetylation-mediated) mechanisms, and explore the potential utility of targeting
      these functions for enhancing drug sensitivity of cancer cells.

PMID- 18715143
TI  - Going ape as an approach to cancer therapeutics.
AB  - The DNA base excision repair (BER) pathway repairs alkylation and oxidative DNA
      damage caused by endogenous and exogenous agents, including chemotherapeutic
      agents. Upon removal of the damaged base AP endonuclease 1 (Ape1), a critical
      component of the pathway cleaves the abasic site to facilitate repair. Ape1 is a
      multifunctional protein which plays a role not only in DNA repair but it also
      functions as a reduction-oxidation factor, known as Ref-1 in the literature, to
      increase the DNA binding ability of several transcription factors involved in
      different growth signaling pathways. Elevated levels of Ape1 have been linked to
      resistance to chemotherapy, poor prognosis, and poor survival. Reducing the
      amount of Ape1 protein in cancer cells and tumors using RNA interference and anti
      sense oligonucleotide technology sensitizes mammalian tumor cells to a variety of
      laboratory and chemotherapeutic agents. Therefore, selective inhibition of Ape1's
      DNA repair activity is a promising avenue to develop novel cancer therapeutics.

PMID- 18715147
TI  - Targeting oxidative stress for neuroprotection.

PMID- 18715149
TI  - Overexpression of methionine sulfoxide reductases A and B2 protects MOLT-4 cells
      against zinc-induced oxidative stress.
AB  - Among the amino acids, methionine is the most susceptible to oxidation, and
      methionine sulfoxide can be catalytically reduced within proteins by methionine
      sulfoxide reductase A (MsrA) and B (MsrB). As one of the very few repair systems
      for oxidized proteins, MsrA and MsrB enzymes play a major role in protein
      homeostasis during aging and have also been involved in cellular defenses against
      oxidative stress, by scavenging reactive oxygen species. To elucidate the role of
      zinc on the Msr system, the effects of zinc treatment on control and stably
      overexpressing MsrA and MsrB2 MOLT-4 leukemia cells have been analyzed. Here we
      show that zinc treatment has a pro-antioxidant effect in MOLT-4 cells by inducing
      the transcription of metallothioneins and positively modulating the activity of
      the Msr enzymes. In contrast, due to its pro-oxidant effect, zinc also led to
      increased cell death, reactive oxygen species production, and protein damage. Our
      results indicate that overexpression of the Msr enzymes, due to their antioxidant
      properties, counteracts the pro-oxidant effects of zinc treatment, which lead to
      a cellular protection against protein oxidative damage and cell death, by
      reducing the production of reactive oxygen species.

PMID- 18715150
TI  - NADPH oxidase drives cytokine and neurotoxin release from microglia and
      macrophages in response to HIV-Tat.
AB  - Previous reports have shown that the human immunodeficiency virus (HIV)
      regulatory protein Tat has both pro-oxidant and pro-inflammatory properties,
      suggesting that Tat might contribute to the neurological complications of HIV.
      However, the intracellular mechanisms whereby Tat triggers free radical
      production and inflammation, and the relationship between Tat-induced free
      radicals and inflammatory reactions, are still subject to debate. The present
      study was undertaken to evaluate the specific effects of Tat on NADPH oxidase in
      microglia and macrophages, and to determine the specific role of NADPH oxidase in
      Tat-induced cytokine/chemokine release and neurotoxicity. Application of Tat to
      microglia or macrophages caused dose- and time-dependent increases in superoxide
      formation that were prevented by both pharmacologic NADPH oxidase inhibitors and
      by specific decoy peptides (gp91ds). Furthermore, inhibition of NADPH oxidase
      attenuated Tat-induced release of interleukin-6 (IL-6), tumor necrosis factor
      alpha (TNF), and monocyte chemoattractant protein 1 (MCP-1), and decreased
      microglial-mediated neurotoxicity. Finally, macrophages derived from NADPH
      oxidase-deficient mice displayed reduced superoxide production, released lower
      levels of cytokines/chemokines, and induced less neurotoxicity in response to Tat
      compared to wild-type macrophages. Together, these data describe a specific and
      biologically significant signaling component of the macrophage/microglial
      response to Tat, and suggest the neuropathology associated with HIV infection
      might originate in part with Tat-induced activation of NADPH oxidase.

PMID- 18715148
TI  - Nitric oxide in health and disease of the nervous system.
AB  - Nitric oxide (NO) is an important messenger molecule in a variety of
      physiological systems. NO, a gas, is produced from L-arginine by different
      isoforms of nitric oxide synthase (NOS) and serves many normal physiologic
      purposes, such as promoting vasodilation of blood vessels and mediating
      communication between nervous system cells. In addition to its physiologic
      actions, free radical activity of NO can cause cellular damage through a
      phenomenon known as nitrosative stress. Here, we review the role of NO in health
      and disease, focusing on its role in function and dysfunction of the nervous
      system. Substantial evidence indicates that NO plays a key role in most common
      neurodegenerative diseases, and, although the mechanism of NO-mediated
      neurodegeneration remains uncertain, studies suggest several possibilities. NO
      has been shown to modify protein function by nitrosylation and nitrotyrosination,
      contribute to glutamate excitotoxicity, inhibit mitochondrial respiratory
      complexes, participate in organelle fragmentation, and mobilize zinc from
      internal stores. In this review, we discuss and analyze the evidence for each of
      these mechanisms in different neurodegenerative diseases and propose future
      directions for research of the role of NO in neurodegeneration.

PMID- 18715152
TI  - Preventing ventilator-associated pneumonia in the United States: a multicenter
      mixed-methods study.
AB  - OBJECTIVE: To determine what practices are used by hospitals to prevent
      ventilator-associated pneumonia (VAP) and, through qualitative methods, to
      understand more fully why hospitals use certain practices and not others. DESIGN:
      Mixed-methods, sequential explanatory study. METHODS: We mailed a survey to the
      lead infection control professionals at 719 US hospitals (119 Department of
      Veterans Affairs [VA] hospitals and 600 non-VA hospitals), to determine what
      practices are used to prevent VAP. We then selected 14 hospitals for an in-depth
      qualitative investigation, to ascertain why certain infection control practices
      are used and others not, interviewing 86 staff members and visiting 6 hospitals.
      RESULTS: The survey response rate was 72%; 83% of hospitals reported using
      semirecumbent positioning, and only 21% reported using subglottic secretion
      drainage. Multivariable analyses indicated collaborative initiatives were
      associated with the use of semirecumbent positioning but provided little guidance
      regarding the use of subglottic secretion drainage. Qualitative analysis,
      however, revealed 3 themes: (1) collaboratives strongly influence the use of
      semirecumbent positioning but have little effect on the use of subglottic
      secretion drainage; (2) nurses play a major role in the use of semirecumbent
      positioning, but they are only minimally involved with the use of subglottic
      secretion drainage; and (3) there is considerable debate about the evidence
      supporting subglottic secretion drainage, despite a meta-analysis of 5 randomized
      trials of subglottic secretion drainage that generally supported this preventive
      practice, compared with only 2 published randomized trials of semirecumbent
      positioning, one of which concluded that it was ineffective at preventing the
      development of VAP. CONCLUSION. Semirecumbent positioning is commonly used to
      prevent VAP, whereas subglottic secretion drainage is used far less often. We
      need to understand better how evidence related to prevention practices is
      identified, interpreted, and used to ensure that research findings are reliably
      translated into clinical practice.

PMID- 18715153
TI  - Secular trends in candidemia-related hospitalization in the United States, 2000
      2005.
AB  - In the United States, from January 1, 2000, through December 31, 2005, the
      incidence of candidemia-related hospitalization per 100,000 population rose by
      52%, from 3.65 to 5.56 cases; and the incidence per 1,000 hospitalizations rose
      by 49%, from 0.28 to 0.42 cases. The proportion of all candidemia-related
      hospitalizations in which candidemia was the principal diagnosis remained stable
      at approximately 14%.

PMID- 18715151
TI  - Apurinic/apyrimidinic endonuclease/redox effector factor-1(APE/Ref-1): a unique
      target for the prevention and treatment of human melanoma.
AB  - Management of melanoma is a growing and challenging public health issue requiring
      novel and multidisciplinary approaches to achieve more efficient prevention and
      therapeutic benefits. The aim of this article is to show the critical role of
      APE/Ref-1 on melanomagenesis and progression. APE/Ref-1 serves as a redox
      sensitive node of convergence of various signals as well as a DNA-repair enzyme,
      and its activation protects melanocytes and melanoma cells from chronic oxidative
      stress and promotes cell survival via mediation of downstream pathways. APE/Ref-1
      is a strong candidate as a potential drug-treatable target for the prevention and
      treatment of human melanoma. Lead compounds exhibiting inhibitory effects on
      APE/Ref-1 are also reviewed. We anticipate potential clinical benefit in the
      future through inhibition of APE/Ref-1 and/or Ref-1-mediated signaling.

PMID- 18715154
TI  - Normalization of serum rapid plasma reagin titer predicts normalization of
      cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis.
AB  - BACKGROUND: Success of neurosyphilis treatment is defined by normalization of
      cerebrospinal fluid (CSF) and clinical abnormalities. The goal of this study was
      to determine whether normalization of serum rapid plasma reagin (RPR) titer could
      accurately predict treatment success. METHODS: One hundred ten patients who were
      enrolled in a longitudinal study of CSF abnormalities in syphilis had
      asymptomatic syphilitic meningitis, symptomatic syphilitic meningitis, or
      syphilitic eye disease and were treated for neurosyphilis. At 4, 7, and 13 months
      after treatment, serum RPR titer and CSF and clinical abnormalities were analyzed
      for normalization. Odds ratios for normalization of each CSF and clinical
      abnormality when serum RPR titer had normalized and the positive predictive value
      of normalization of serum RPR titer for normalization of CSF and clinical
      abnormalities were determined. RESULTS: Serum RPR titer had normalized in 63
      patients (57%) by 4 months after treatment, in 94 (85%) by 7 months, and in 97
      (88%) by 13 months. Except for CSF protein concentration, normalization of serum
      RPR titer predicted normalization of other CSF and clinical abnormalities in >80%
      of patients at 4 months, >85% at 7 months, and >90% at 13 months. The odds of
      normalization of CSF and clinical abnormalities were 28-57-fold higher when serum
      RPR titer had normalized, compared with when it had not. Normalization of serum
      RPR titer was consistently less accurate in predicting treatment success in human
      immunodeficiency virus-infected patients who were not receiving antiretroviral
      therapy, compared with those who were receiving such therapy. CONCLUSIONS: In
      most instances, normalization of serum RPR titer correctly predicts success of
      treatment of neurosyphilis, and follow-up lumbar puncture can be avoided.

PMID- 18715155
TI  - A multicenter, cross-sectional study on the prevalence and risk factors for nasal
      colonization with Staphylococcus aureus in patients admitted to children's
      hospitals in Switzerland.
AB  - The rate of nasal carriage of Staphylococcus aureus and associated risk factors
      were determined in a cross-sectional study involving Swiss children's hospitals.
      S. aureus was isolated in 562 of 1363 cases. In a stepwise multivariate analysis,
      the variables age, duration of antibiotic use, and hospitalization of a household
      member were independently associated with carriage of S. aureus.

PMID- 18715156
TI  - Clinical outcomes of hepatitis C treatment in a prison setting: feasibility and
      effectiveness for challenging treatment populations.
AB  - BACKGROUND: More than one-third of people in the United States with hepatic C
      virus (HCV) infection pass through the correctional system annually. Data are
      lacking on outcomes of treatment with pegylated interferon plus ribavirin (PEG
      RBV) in correctional settings. METHODS: During 2002-2006, we analyzed patients in
      the Connecticut Department of Correction who received PEG-RBV. We assessed the
      rates of sustained virological response, hospitalization, and use of medications
      to treat psychiatric disorders and anemia. RESULTS: Of 138 treatment-naive
      patients referred for treatment, 68 (49%) were approved. Overall, sustained
      virological response occurred in 47.1% of patients (for HCV genotype 1, 43.1%;
      for HCV genotypes 2 and 3, 58.8%). Only 9 patients (13%) discontinued treatment
      because of adverse effects. Multiple regression analysis revealed that not
      achieving a sustained virological response was correlated with HCV genotype 1
      infection plus cirrhosis (adjusted odds ratio, 12.9; 95% confidence interval, 1.1
      148) and baseline major depression (adjusted odds ratio, 3.4; 95% confidence
      interval, 1.01-11.6), but not with HIV infection, a baseline HCV RNA level
      >or=400,000 IU/mL, or black race. Compared with baseline, the rate of
      prescription of a new mood stabilizer (2.2 vs. 0.8 prescriptions per person-year)
      or an opioid (1.8 vs. 0.5 prescriptions per person-year) was higher during
      treatment, whereas there was no change in the rate of prescription of
      benzodiazepines and antipsychotic medications. CONCLUSIONS: These results support
      the feasibility and clinical effectiveness of PEG-RBV for the treatment of
      chronic HCV infection in correctional facilities.

PMID- 18715157
TI  - Extensively drug-resistant Mycobacterium tuberculosis during a trend of
      decreasing drug resistance from 2000 through 2006 at a Medical Center in Taiwan.
AB  - BACKGROUND: Drug resistance rates are one of the most important aspects in the
      national tuberculosis (TB) control program, and drug-resistant TB, especially
      extensively drug-resistant (XDR) TB, is not well understood in Taiwan. The
      objectives of this study were to investigate the prevalence of drug resistance
      from 2000 through 2006 and to identify XDR TB isolates to elucidate the clinical
      characteristics of patients with XDR TB at National Taiwan University Hospital.
      METHODS: The prevalence of drug resistance among clinical, nonduplicate
      Mycobacterium tuberculosis isolates was analyzed. Testing of susceptibility to
      antituberculosis agents, including isoniazid, rifampicin, ethambutol,
      streptomycin, rifabutin, ofloxacin, ethinamide, and para-aminosalicylic acid, was
      performed using the proportional method. Minimum inhibitory concentrations of
      amikacin, capreomycin, isepamycin, linezolid, cycloserine, ciprofloxacin,
      levofloxacin, moxifloxacin, and gemifloxacin were determined for 40 available
      multidrug-resistant M. tuberculosis isolates. RESULTS: Significant decreasing
      trends in rates of resistance to isoniazid, ethambutol, and at least 1 of the 3
      first-line agents were observed among 2625 M. tuberculosis isolates from 2000
      through 2006. Among these 2625 isolates, 150 (5.7%) were multidrug resistant, and
      10 M. tuberculosis isolates (0.4%) fulfilled the definition of XDR M.
      tuberculosis. Nine (90%) of 10 patients with XDR TB had a previous history of TB
      and received anti-TB treatment before acquisition of XDR TB. CONCLUSIONS: The
      remaining high prevalence of multidrug-resistant TB and the presence of XDR TB
      during a trend of decreasing drug resistance are alarming. Continuous
      surveillance of clinical isolates of M. tuberculosis is needed to identify XDR
      TB, especially in patients who have a history of TB and have received prior anti
      TB treatment.

PMID- 18715158
TI  - Neurosyphilis: diagnosis and response to treatment.

PMID- 18715159
TI  - Cryptosporidiosis in children in Sub-Saharan Africa: a lingering challenge.
AB  - Hospital- and community-based studies in sub-Saharan Africa document a high
      prevalence of cryptosporidiosis in children aged 6-36 months, particularly among
      those who are malnourished or positive for human immunodeficiency virus (HIV)
      infection and during rainy seasons. This is despite advances in developed
      countries that have curbed the incidence of cryptosporidiosis in the general and
      HIV-positive populations. Transmission in sub-Saharan Africa appears to occur
      predominantly through an anthroponotic cycle. The preponderance of
      Cryptosporidium hominis, given its limited host range, and the dominance of the
      more ubiquitous Cryptosporidium parvum after coexposure to both species, however,
      suggest that the current knowledge of transmission is incomplete. Given the poor
      sanitation and hygiene, limited availability of antiretrovirals, and the high
      prevalence of cryptosporidiosis in children-independent of HIV infection-in this
      region, effective control measures for cryptosporidiosis are desperately needed.
      Molecular targets from the recently sequenced parasite genome should be exploited
      to develop an effective and safe treatment for children.

PMID- 18715160
TI  - A randomized, double-blind, placebo-controlled trial to evaluate the prime-boost
      strategy for pneumococcal vaccination in adult liver transplant recipients.
AB  - BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPV23) is
      recommended for disease prevention in solid-organ transplant recipients, but it
      may have suboptimal immunogenicity. It may be possible to enhance immunogenicity
      by priming the recipient with the 7-valent pneumococcal conjugate vaccine (PCV7),
      followed by boosting with PPV23. METHODS: We randomized adult liver transplant
      recipients to receive either (1) PCV7 followed by a PPV23 booster 8 weeks later
      (the "primed" group) or (2) placebo followed by a standard single dose of PPV23
      (the "unprimed" group). Quantitative and functional antibody titers for 7
      serotypes contained in both vaccines were measured at baseline, 8 weeks after
      enrollment, and 16 weeks after enrollment. Of 130 randomized patients, 113
      completed the study. RESULTS: At week 16, response to at least 1 serotype was
      seen in 48 (85.7%) of 56 and 52 (91.2%) of 57 patients for the primed and
      unprimed groups, respectively (P=not significant). The mean number of serotypes
      to have responded (+/-SD) was 307+/-2.3 and 4.4+/-2.2 for the primed and unprimed
      groups, respectively (P=not significant). Functional antibody titers, which were
      measured with use of the opsonophagocytic assay, were also similar in both
      groups. CONCLUSIONS: The immunogenicity of pneumococcal vaccination was not
      enhanced by the prime-boost strategy, compared with vaccination with PPV23 alone.
      Administration of a single dose of PPV23 should continue to be the standard of
      care for adult liver transplant recipients. CLINICAL TRIALS REGISTRATION:
      NCT00152802 (http://www.clinicaltrials.gov).

PMID- 18715161
TI  - Hormonal contraception and HIV disease progression.
AB  - The majority of the 15.4 million human immunodeficiency virus (HIV)-infected
      women worldwide are of child-bearing age and need access to contraception.
      Hormonal methods of contraception are safe, acceptable, and effective in
      preventing unwanted pregnancies. Many published studies have examined the impact
      of hormonal contraception on HIV disease acquisition and transmissibility. Far
      fewer have investigated the relationship between hormonal contraception and HIV
      disease progression. This review examines available data on this relationship
      from clinical, animal, and immunological studies. Several clinical studies
      suggest an overall effect but are not definitive, and the mechanisms behind HIV
      disease progression are unclear. Animal and immunological data suggest that
      immunomodulation by hormonal contraceptive methods may affect the immune response
      to HIV infection. Additional work is needed in this area to elucidate the
      possible relationship between hormonal methods for birth control and progression
      to acquired immunodeficiency syndrome in HIV-infected women.

PMID- 18715162
TI  - High mobility group box 1 protein inhibits the proliferation of human mesenchymal
      stem cells and promotes their migration and differentiation along osteoblastic
      pathway.
AB  - Extracellular high mobility group box 1 (HMGB1) is a novel cytokine that takes
      part in the processes of inflammation, tissue damage and regeneration.
      Mesenchymal stem cells (MSCs) are adult stem cells characterized by their
      inherently suppressive activities on inflammative and allo-immune reactions. In
      the present study, we have addressed whether HMGB1 could affect the biological
      properties of human bone marrow MSCs. Transwell experiments showed that HMGB1
      induced MSC migration and this effect could not be hampered by a blocking
      antibody against the receptor for advanced glycation end products (RAGE). MSCs
      exposed to HMGB1 were negative for CD31, CD45, CD80, and HLA-DR, and displayed
      equal levels of CD73, CD166, and HLA-ABC compared with their counterparts, but
      HMGB1 profoundly suppressed MSC proliferation in a dose-dependent manner as
      evaluated by carboxyfluorescein diacetate succinmidyl ester dye dilution assay.
      Furthermore, HMGB1 triggered the differentiation of MSCs into osteoblasts as
      identified by histochemical staining, traditional RT-PCR and real-time RT-PCR
      analysis on mRNA expression of lineage-specific molecular markers. The
      differentiation-inductive activity could neither be inhibited by RAGE
      neutralizing antibody. Moreover, HMGB1-treated MSCs displayed unchanged
      suppressive activity on in vitro lymphocyte cell proliferation elicited by ConA.
      Collectively, the data suggest that MSCs are a target of HMGB1.

PMID- 18715165
TI  - Oncologists and end-of-life care.

PMID- 18715166
TI  - Preparing for the hospice and palliative medicine certification examination.

PMID- 18715167
TI  - Audit of resource utilization in a regional palliative care program using the
      Edmonton Classification System for Cancer Pain (ECS-CP).

PMID- 18715168
TI  - Physician-nurse staffing on palliative care consultation services.

PMID- 18715169
TI  - Palliative sedation and physician-assisted death.

PMID- 18715170
TI  - Re: Is there a higher risk of respiratory depression in opioid-naive palliative
      care patients during symptomatic therapy of dyspnea with strong opioids?

PMID- 18715171
TI  - Outpatient clinics are a new frontier for palliative care.

PMID- 18715172
TI  - Combining objective and subjective outcomes in cancer-related fatigue:
      illustrations from a single case report.
AB  - Neurophysiologic measurements were made on a patient with multiple lung cancers
      and severe cancer-related fatigue (CRF) who responded to 5 mg methylphenidate
      twice daily, titrated to 10 mg twice daily after 2 weeks. She remained at 10 mg
      twice daily for 8 months. Improvement in severe CRF (Brief Fatigue Inventory
      score) was associated with normalization of neurophysiologic tests.

PMID- 18715173
TI  - Skin findings in palliative care patients.
AB  - The prevalence of dermatologic disease and its effect on quality of life has not
      been well studied in patients with advanced illness. We sought to describe skin
      findings in inpatient palliative care patients and determine how often they are
      addressed by the primary or palliative care teams. We collected patient
      demographic and clinical data from the medical record, performed total body skin
      examinations, and determined how often significant cutaneous findings were
      documented in the chart. We also characterized skin findings as uncomfortable and
      treatable. Twenty palliative care patients participated in the study over a 2
      month period. Common findings included skin breakdown (20/54; 37%), skin
      infections (14/54; 26%), inflammatory dermatoses (9/54; 17%), and skin conditions
      related to systemic disease (7/54; 13%) or treatment of systemic disease (4/54;
      7%). Most of these conditions were not documented by primary or palliative care
      clinicians. Eighty percent of the patients had uncomfortable, but treatable skin
      conditions of which 62% (13/21) were undocumented or incorrectly documented.
      These limited data suggest the need for palliative care clinicians to conduct
      more complete skin examinations, and to improve their knowledge of common skin
      abnormalities in patients with serious illness. A larger scale investigation of
      skin disease and its effect on quality of life in the palliative care population
      is warranted.

PMID- 18715174
TI  - Myoclonus associated with high-dose parenteral methadone.
AB  - Methadone is generally believed to be devoid of neuroexcitatory properties, and
      its use is increasing. This paper reports two cases of myoclonus with high-dose
      parenteral methadone in patients with cancer under hospice care. This side effect
      may be dose related and/or due to the parenteral route of administration.
      Reduction of the dose and change of route was sufficient to eliminate the
      myoclonus while maintaining an adequate pain control. Possible mechanisms for
      methadone causing myoclonus include a redistribution of receptor saturation in
      the N-methyl-D-aspartate (NMDA) and delta receptors. Ketamine may be an option
      for patients with intractable pain who develop methadone-induced myoclonus.

PMID- 18715175
TI  - Using metaphors in medicine.

PMID- 18715176
TI  - A winding career path.

PMID- 18715177
TI  - Marital status and health: exploring pre-widowhood.
AB  - BACKGROUND: Health and function vary by marital status across the life-course,
      but little is known about older adults approaching spousal loss (pre-widowed).
      OBJECTIVE: To explore health and function by marital status focusing on the pre
      widowed and to examine factors associated with shorter time to spousal loss.
      PARTICIPANTS, DESIGN, AND MEASUREMENTS: We used 3 years of data from African
      American and white community-dwelling older adults in the UAB Study of Aging (N =
      1000). Participants were categorized as "continuously married" (married at
      baseline and 3 years), "widowed" (widowed at baseline), "single" (never
      married/divorced); and "pre-widowed" (married at baseline and widowed within 3
      years). Assessments included sociodemographic characteristics, and measures of
      depression, anxiety, life-space mobility, and self-reported health. chi(2) and
      analysis of variance (ANOVA) were used to examine baseline differences. Using Cox
      regression, we explored factors having independent and significant associations
      with shorter time to spousal loss among married older adults. RESULTS: There were
      significant differences by marital status category for sociodemographic factors,
      health, and function. Pre-widows differed from other categories by
      sociodemographic characteristics as well as levels of depression, anxiety and
      self-reported health. Among married older adults, being female and having lower
      self-reported health at baseline were independent significant hazards for shorter
      time to widowhood; while rural residence and providing spousal care were
      independent significant hazards for a longer progression to widowhood.
      CONCLUSIONS: Health deficits associated with spousal bereavement may be evident
      earlier in the marital transition than previously thought, warranting attention
      to the health of elderly persons whose spouses have chronic/life-limiting
      conditions.

PMID- 18715178
TI  - Assessment of implementation of an order protocol for end-of-life symptom
      management.
AB  - OBJECTIVES: Designing comfort care plans to treat symptoms at the end-of-life in
      the hospital is challenging. We evaluated the implementation of an inpatient end
      of-life symptom management order (ESMO) protocol that guides the use of opiate
      medications and other modalities to provide palliation. METHODS: Physicians and
      nurses caring for patients using the ESMO protocol were surveyed about care
      provided and their experiences. RESULTS: Over 342 days, 127 patients (2.6 per
      week) were treated using the ESMO protocol and we surveyed a nurse and/or
      physician for 105 (83%) patients. Most patients were comatose,
      obtunded/stuperous, or disoriented when the ESMO protocol was initiated and most
      had a life expectancy of less than 1 day. One fourth of physicians felt that the
      protocol was instituted too late, principally citing family unwillingness to
      reorient toward comfort care. Providers reported that opiates were titrated
      appropriately, although a minority revealed discomfort with end-of-life opiate
      use. Nearly all clinicians found the ESMO protocol to be valuable. CONCLUSIONS: A
      standardized protocol is a useful, but not fully sufficient, step toward
      improving care for dying hospitalized patients.

PMID- 18715179
TI  - End-of-life care in U.S. nursing homes: nursing homes with special programs and
      trained staff for hospice or palliative/end-of-life care.
AB  - BACKGROUND: The degree to which nursing homes have internal programs for hospice
      and palliative care is unknown. We used self-reported data from the 2004 National
      Nursing Home Survey (NNHS) to estimate the prevalence of special programs and
      (specially) trained staff (SPTS) for hospice or palliative/end-of-life care in
      U.S. nursing homes. Factors associated with the presence of SPTS for hospice or
      palliative/end-of-life care were identified. METHODS: We merged 2004 NNHS data
      for 1174 nursing homes to county-level data from the 2004 Area Resource File and
      to Nursing Home 2004 Online Survey, Certification, and Reporting data. chi(2)
      tests and logistic regression models were applied. RESULTS: Twenty-seven percent
      of U.S. nursing homes reported (internal) SPTS for hospice or palliative/end-of
      life care. After controlling for covariates, we found nonprofit status, being in
      the southern region of the United States, having an administrator certified by
      the American College of Health Care Administrators, contracting with an outside
      hospice provider, and having other specialty programs to be associated with a
      greater likelihood of nursing homes having SPTS for hospice or palliative/end-of
      life care. The largest effects were observed for nursing homes with programs for
      behavioral problems (adjusted odds ratio [AOR] 3.59; 95% confidence interval [CI]
      2.40, 5.37) and for pain management (AOR 5.92; 95% CI 4.09, 8.57). CONCLUSION:
      The presence of internal SPTS for hospice or palliative/end-of-life care is
      prevalent in U.S. nursing homes, and may be preceded by hospice contracting
      and/or the implementation of specialty programs that assist nursing homes in
      developing the expertise needed to establish their own palliative care programs.

PMID- 18715180
TI  - Factors associated with falls in patients with cancer hospitalized for palliative
      care.
AB  - INTRODUCTION: In geriatrics, most risk factors associated with falls have been
      identified and management strategies developed accordingly. This is not the case
      in palliative care. The incidence rate of falls, the consequences related to
      falls, and other related factors were determined in elderly cancer patients
      hospitalized for palliative care in an exploratory study. METHODS: All
      consecutive patients hospitalized with advanced cancer were included over a 1
      year period. Each fall was identified and detailed by a routinely collected
      incident report. Associations between variables and falls were assessed. RESULTS:
      Mean age of the 198 patients (116 F) was 71.0 +/- 12.1 years. Of these, 36 had a
      fall at least once. Delirium occurred significantly more often in fallers (p =
      0.029). There was a nonsignificant trend for a higher number of prescribed drugs
      in fallers (n = 8.5 +/- 3.7 versus 7.5 +/- 3.2; p = 0.4) who received
      significantly more neuroleptics (47.2% versus 29%; p = 0.035). Environmental
      hazards made little contribution to patients' falls. DISCUSSION: Characteristics
      of falls in palliative care appear different from those evidenced in geriatric
      wards. To prevent delirium while prescribing neuroleptic drugs with the greatest
      caution should help decrease the number of falls in this highly vulnerable group
      of patients.

PMID- 18715181
TI  - Breaking bad news: use of cancer survivors in role-playing exercises.
AB  - PURPOSE: To teach medical students how to deliver a diagnosis of cancer using
      role-play with a cancer survivor volunteer. METHOD: Medical students participated
      in a curricular module on "breaking bad news." Its novel aspect was the inclusion
      of role-playing exercises during which the student communicated the initial
      diagnosis of cancer to a cancer survivor volunteer. The clinical scenario was
      based on the volunteer's own history of cancer. The exercise required the student
      to become knowledgeable about the volunteer's cancer and its mode of
      presentation, deliver the diagnosis using previously demonstrated methods, and
      then receive verbal feedback from the volunteer. A panel discussion with the
      cancer survivor volunteers concluded the module. The efficacy of this curricular
      module was assessed by the students' performance during the role-playing
      exercise, gain in confidence in communicating bad news, and overall rating of the
      learning experience. RESULTS: The interaction of the students with the cancer
      survivors was the strength of this curriculum, providing the students with an
      important perspective on physician-patient relationships and coping with cancer.
      The students demonstrated a high level of adherence to preferred communication
      techniques, gained significant confidence with the task of "breaking bad news,"
      and were very satisfied with the module. Participation in these role-playing
      exercises by the cancer survivor volunteers was viewed as emotionally demanding
      but also rewarding. Recruitment and retention of the volunteers were not
      obstacles to this activity. CONCLUSION: Role-playing with cancer survivor
      volunteers can be an effective method of teaching medical students how to
      communicate bad news.

PMID- 18715182
TI  - A qualitative study of oncologists' approaches to end-of-life care.
AB  - PURPOSE: To understand how oncologists provide care at the end of life, the
      emotions they experience in the provision of this care, and how caring for dying
      patients may impact job satisfaction and burnout. PARTICIPANTS AND METHODS: A
      face-to-face survey and in-depth semistructured interview of 18 academic
      oncologists who were asked to describe the most recent inpatient death on the
      medical oncology service. Physicians were asked to describe the details of the
      patient death, their involvement with the care of the patient, the types and
      sequence of their emotional reactions, and their methods of coping. Grounded
      theory qualitative methods were utilized in the analysis of the transcripts.
      RESULTS: Physicians, who viewed their physician role as encompassing both
      biomedical and psychosocial aspects of care, reported a clear method of
      communication about end-of-life (EOL) care, and an ability to positively
      influence patient and family coping with and acceptance of the dying process.
      These physicians described communication as a process, made recommendations to
      the patient using an individualized approach, and viewed the provision of
      effective EOL care as very satisfying. In contrast, participants who described
      primarily a biomedical role reported a more distant relationship with the
      patient, a sense of failure at not being able to alter the course of the disease,
      and an absence of collegial support. In their descriptions of communication
      encounters with patients and families, these physicians did not seem to feel they
      could impact patients' coping with and acceptance of death and made few
      recommendations about EOL treatment options. CONCLUSION: Physicians' who viewed
      EOL care as an important role described communicating with dying patients as a
      process and reported increased job satisfaction. Further research is necessary to
      determine if educational interventions to improve physician EOL communication
      skills could improve physician job satisfaction and decrease burnout.

PMID- 18715183
TI  - Providers and types of spiritual care during serious illness.
AB  - OBJECTIVE: Patients and palliative care experts endorse the importance of
      spiritual care for seriously ill patients and their families. However, little is
      known about spiritual care during serious illness, and whether it satisfies
      patients' and families' needs. The objective of this study was to describe
      spiritual care received by patients and families during serious illness, and test
      whether the provider and the type of care is associated with satisfaction with
      care. METHODS: Cross-sectional interview with 38 seriously ill patients and 65
      family caregivers about spiritual care experiences. RESULTS: The 103 spiritual
      care recipients identified 237 spiritual care providers; 95 (41%) were family or
      friends, 38 (17%) were clergy, and 66 (29%) were health care providers. Two
      thirds of spiritual care providers shared the recipient's faith tradition.
      Recipients identified 21 different types of spiritual care activities. The most
      common activity was help coping with illness (87%) and the least common
      intercessory prayer (4%). Half of recipients were very or somewhat satisfied with
      spiritual care, and half found it very helpful for facilitating inner peace and
      meaning making. Satisfaction with spiritual care did not differ by provider age,
      race, gender, role, or frequency of visits. Types of care that helped with
      understanding or illness coping were associated with greater satisfaction with
      care. CONCLUSION: Seriously ill patients and family caregivers experience
      spiritual care from multiple sources, including health care providers.
      Satisfaction with this care domain is modest, but approaches that help with
      understanding and with coping are associated with greater satisfaction.

PMID- 18715185
TI  - Conflict resolution I: careful communication #183.

PMID- 18715186
TI  - Conflict resolution II: principled negotiation #184.

PMID- 18715184
TI  - Factors associated with physician decision-making in starting tube feeding.
AB  - BACKGROUND: Because tube-feeding decisions are sometimes difficult, we examined
      physician, institutional, and patient factors associated with these decisions.
      METHODS: Primary care physicians (n = 388) likely to manage nursing home patients
      in Hawaii were surveyed. Respondents indicated the factors of great importance in
      tube feeding decisions based on a vignette of a poststroke patient failing to
      thrive and family disagreement with advance directives. chi(2) and multiple
      logistic regression analyses were used to examine associations between physician
      demographics and factors of importance to physicians and their decisions based on
      the vignette. RESULTS: Starting tube feeding (chosen by 31% of respondents) was
      associated with internal medicine specialty (odds ratio [OR] 2.5, 95% confidence
      interval [CI] 1.4-4.6), and placing great importance on family preference (OR
      5.4, 95% CI 3.0-9.8) and liability (OR 2.5, 95% CI 1.3-4.8). After 3 months
      without improvement, 58% chose to withdraw tube feeding. Continuing tube feeding
      was associated with placing great importance on family wishes (OR 3.0, 95% CI 1.8
      5.1) and liability (OR 1.7, 95% CI 1.0-2.9). Placing great importance on the
      living will was associated with decreased likelihoods of starting (OR 0.1, 95% CI
      0.04-0.3) and continuing (OR 0.1, 95% CI 0.04-0.3) tube feeding. CONCLUSIONS: The
      decision to start or withhold tube feeding is associated with the individual
      physician's perception of the importance of patient wishes versus family wishes
      and liability concerns. Physician awareness of the influence of these factors on
      medical decisions may improve the decision-making process.

PMID- 18715188
TI  - Nabilone for the treatment of paraneoplastic night sweats: a report of four
      cases.
AB  - ABSTRACT Night sweats are one of many symptoms experienced by patients with
      advanced cancer. The prevalence of night sweats ranges from 10%-48% in cancer
      patients. Persistent night sweats tend to decrease quality of life through
      interference with sleep. A recent study has demonstrated that night sweats occur
      as part of a symptom pattern, and are associated with the anorexia-cachexia
      symptom cluster. In addition, night sweats represent one of the symptoms that
      displays a tendency not to improve as patients with advanced cancer approach end
      of life. This paper serves to report on the successful management of four
      patients suffering from persistent paraneoplastic night sweats using the
      synthetic orally administered cannabinoid nabilone. The four patients had been
      referred to a regional consultative palliative medicine program and identified
      night sweats as one of their most significant symptomatic concerns reported on
      their Edmonton Symptom Assessment System (ESAS) questionnaires.

PMID- 18715194
TI  - Opioid-induced neurotoxicity: too much of a good thing.

PMID- 18715196
TI  - BAFF is a biological response marker to IFN-beta treatment in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a complex autoimmune disease characterized by the
      destruction of the myelin sheath of neurons. Interferon beta (IFN-beta) is
      currently the major drug used to treat MS. Some patients fail to respond to this
      treatment, in some cases due to the development of neutralizing antibodies (NAb)
      to IFN-beta. We used microarray analysis and RT-PCR to measure gene expression in
      whole blood, 9-15 h postinjection, in patients with and without NAbs to IFN-beta.
      The canonical marker of biological response to IFN-beta, myxovirus resistance
      protein A, was upregulated in all NAb- patients while remaining unchanged in NAb+
      patients. Genes functioning in immune response pathways were dominant in the set
      of differentially expressed genes: 73 immune response genes were identified as
      upregulated and 29 genes were identified as downregulated. B-cell activating
      factor (BAFF) is a strong candidate marker for biological and clinical response
      as well as for predisposition to NAb development. We demonstrate that it is
      responsive to IFN-beta in vitro and in vivo, and that its soluble form is
      elevated in serum from NAb- but not NAb+ patients. We conclude BAFF is a good
      biomarker for IFN-beta response, and requires further studies to determine its
      value as a marker for clinical response and NAb predisposition.

PMID- 18715198
TI  - Initiating insulin therapy in type 2 diabetes: benefits of insulin analogs and
      insulin pens.
AB  - Despite the development of alternative therapies in recent years, insulin
      injections remain essential treatment for type 2 diabetes once oral therapy alone
      becomes inadequate. However, neither patients nor physicians are proactive enough
      with regard to starting insulin, despite the well-known benefits of early insulin
      initiation and aggressive dose titration. Barriers to starting insulin therapy
      are being overcome by developments in insulin and delivery device technology and
      are the subject of this review. A literature search spanning the last 25 years
      was carried out to identify publications addressing issues of insulin initiation,
      how insulin analogs can help overcome barriers to initiation, and the advantages
      of pen-type insulin delivery systems. Seventy-five publications were identified.
      These references illustrate that the drawbacks associated with regular exogenous
      human insulins (soluble and NPH) are improved with modern insulin analogs. The
      more rapid absorption of prandial insulin analogs compared with human insulin
      eliminates the need for an injection-meal-interval, increasing convenience, while
      basal analogs have no discernible peak in activity. Modern insulin delivery
      devices also have advantages over the traditional vial and syringe. Currently
      available insulin pens are either durable (insulin cartridge is replaceable;
      e.g., HumaPen, Eli Lilly [Indianapolis, IN]; NovoPen series, Novo Nordisk
      [Bagsvaerd, Denmark]) or disposable (prefilled; e.g., FlexPen, Novo Nordisk;
      SoloSTAR, sanofi-aventis [Paris, France]), with features to aid ease-of-use.
      These include a large dose selector, dial-up and dial-down facility, and audible
      clicks when selecting the dose. The potential for dosing errors is thus reduced
      with pen-type devices, with other benefits including a discreet appearance, ease
      of learning, and greater user confidence. Collectively, these features contribute
      to overwhelming patient preference when compared with vials and syringes. Despite
      the greater cost of insulin pens relative to vials and syringes, improvements in
      treatment adherence with pens-and hence glycemic control-may offset these costs
      in the long term.

PMID- 18715197
TI  - Bioinformatic analysis reveals cRel as a regulator of a subset of interferon
      stimulated genes.
AB  - Interferons (IFNs) are critical to the host innate immune response by inducing
      the expression of a family of early response genes, denoted as IFN-stimulated
      genes (ISGs). The role of tyrosine phosphorylation of STAT proteins in the
      transcription activation of ISGs is well-documented. Recent studies have
      indicated that other transcription factors (TFs) are likely to play a role in
      regulating ISG expression. Here, we describe a novel integrative approach that
      combines gene expression profiling, promoter sequence analysis, and literature
      mining to screen candidate regulatory factors in the IFN signal transduction
      pathway. Application of this method identified the nuclear factor kappaB
      (NFkappaB) protein, cRel, as a candidate regulatory factor for a subset of ISGs
      in mouse embryo fibroblasts. Chromatin immunoprecipitation (ChIP) and real-time
      PCR assays confirmed that cRel directly binds to the promoters of several ISGs,
      including Cxcl10, Isg15, Gbp2, Ifit3, and Ifi203, and regulates their expression.
      Thus, our studies identify cRel as an important TF for ISGs, and validate the
      approach of using Latent Semantic Indexing (LSI)-based methods to identify
      regulatory factors from microarray data.

PMID- 18715199
TI  - Progress toward an in vivo surface-enhanced Raman spectroscopy glucose sensor.
AB  - BACKGROUND: In this report, we detail our current work towards developing a
      surface-enhanced Raman spectroscopy (SERS) based sensor for in vivo glucose
      detection. Despite years of innovations in the development of blood glucose
      monitors, there remains a need for accurate continuous glucose sensors to provide
      care to rising numbers of diagnosed diabetes patients and mitigate secondary
      health complications associated with this metabolic disorder. METHODS: SERS is a
      highly specific and sensitive optical technique suitable for direct detection of
      glucose. The SERS effect is highly distance dependent, thus the glucose molecules
      need to be within a few nanometers or adsorbed to an SERS-active surface. In our
      sensor, this is achieved with a self-assembled monolayer (SAM) that facilitates
      reversible interactions between glucose molecules and the surface. The amount of
      glucose near the surface is proportional to its concentration in the surrounding
      environment. RESULTS: We determined that the SAM-functionalized surface is stable
      for at least 10 days and provides rapid, reversible partitioning. In vitro
      experiments in bovine plasma as well as in vivo experiments in rats demonstrated
      quantitative detection. CONCLUSIONS: We show successful use of the SERS glucose
      sensor in rats, making it the first in vivo SERS sensor. Furthermore, we
      demonstrate free space transdermal detection of a SERS signal through the rat's
      skin as an initial step toward developing a transcutaneous sensor.

PMID- 18715200
TI  - Reduced weight gain with insulin detemir compared to NPH insulin is not explained
      by a reduction in hypoglycemia.
AB  - BACKGROUND: Weight gain often occurs when insulin therapy is initiated. The long
      acting insulin analog insulin detemir has been shown to be effective and well
      tolerated when used in basal-bolus regimens or as an add-on to oral antidiabetic
      drugs (OADs) and causes less weight gain than other insulins. The aim of this
      exploratory analysis was to investigate any correlations between weight change
      and occurrence of hypoglycemia with NPH insulin and insulin detemir. METHODS: The
      analysis was based on a 26-week, randomized, multicenter, open-label, parallel
      group trial in which glycemic control, hypoglycemia, and weight change were
      compared between insulin detemir and NPH insulin. A total of 476 insulin-naive
      patients with type 2 diabetes treated with one or two OADs added insulin detemir
      (n=237) or NPH insulin (n=239) morning and evening to their current oral
      treatment. Weight gain data from this study were analyzed as a function of
      hypoglycemia frequency. RESULTS: Both groups achieved excellent glycosylated
      hemoglobin control (insulin detemir, 6.6%; NPH insulin, 6.5% [difference not
      significant]). Weight gain with insulin detemir was less than half that of NPH
      insulin (1.2 vs. 2.8 kg, respectively [P<0.001]), and the overall risk of
      hypoglycemia was 47% lower with insulin detemir (P<0.001). No significant
      relationship between hypoglycemia and weight gain was seen with insulin detemir
      (P=0.2), while a statistically significant correlation was found for NPH insulin
      (P=0.003). CONCLUSIONS: Hypoglycemia is predictive of weight gain with NPH
      insulin, but the same relationship is not seen with insulin detemir. It is
      therefore likely that the weight-sparing effect of insulin detemir involves other
      mechanisms.

PMID- 18715201
TI  - Influence of diabetes on the validity glaucoma screening by frequency doubling
      perimetry: a hospital-based study in Oman.
AB  - BACKGROUND: A hospital-based study was conducted in 2007 in Oman to determine the
      validity of frequency doubling perimetry (FDP). The authors have compared the
      ability of FDP to detect glaucoma among patients with and without diabetes.
      METHODS: This was a validity study of the screening procedure. An ophthalmologist
      and an optometrist examined Omani persons >30 years of age with and without
      diabetes. They determined glaucomatous field changes by using FDP. The glaucoma
      specialist labeled the eye and the person as suffering from glaucoma if two
      criteria were present: (1) optic cup disc and other retinal changes suggestive of
      glaucoma and (2) field changes on automated perimeter suggestive of glaucoma.
      Ocular pressure was measured with a Tono-Pen (Medtronic Ophthalmics,
      Jacksonville, FL). We calculated the validity of glaucoma screening by FDP among
      persons both with diabetes and without diabetes. RESULTS: We examined 111 eyes of
      56 Omani patients (55 eyes of 28 patients with diabetes and 56 eyes of 28 persons
      without diabetes). Two persons had a history of glaucoma in both eyes. Glaucoma
      screening by FDP detected five eyes (two eyes of patients with diabetes and three
      eyes of persons without diabetes) with glaucoma. The specificity of glaucoma
      screening among those with and without diabetes was 97.4% and 97.3%,
      respectively. The sensitivity was 6% and 11%, respectively, in these two groups.
      CONCLUSIONS: Validity of glaucoma screening by FDP is not different among those
      with and without diabetes. In countries with high rates of diabetes, FDP could be
      used as a first-level screening tool for glaucoma.

PMID- 18715202
TI  - Modeling glucose and water dynamics in human skin.
AB  - BACKGROUND: Glucose is heterogeneously distributed in the different physiological
      compartments in the human skin. Therefore, for the development of a noninvasive
      measurement method, both a good quantification of the different compartments of
      human skin and an understanding of glucose transport processes are important.
      METHODS: The composition of human skin was quantified by histology research.
      Based on this information a mathematical model was developed to simulate glucose
      dynamics in human skin. RESULTS: The model predicts dynamically glucose
      concentrations in the different layers of the skin as a result of changes in
      blood glucose concentration. The model was validated with published time course
      data of blood and interstitial fluid glucose during a clamp study with three
      different set points for blood glucose, and model outcomes were compared to
      measurements for the lag time and gradient. According to the model, glucose in
      the interstitial fluid of the dermis best matches the amplitude and dynamics of
      blood glucose. CONCLUSIONS: The new data obtained from quantitative histology
      appeared crucial for the model. The proposed model was successfully validated.
      This result was obtained without tuning or fitting of any parameter. It was shown
      how the model can be used to set standards for measurements and to define the
      best measurement depth for noninvasive glucose monitoring.

PMID- 18715203
TI  - The effects of magnetic field on the biomechanics parameters of soleus and
      extensor digitorum longus muscles in rats with streptozotocin-induced diabetes.
AB  - BACKGROUND: The aim of this study was to determine the effects of the magnetic
      field (MF) on the isometric contractile characteristics of the soleus and
      extensor digitorum longus (EDL) muscles in rats both with and without diabetes.
      METHODS: Biomechanical parameters were recorded in vitro from Wistar rats without
      diabetes (Group I, n=20), rats without diabetes exposed to MF (Group II, n=20),
      rats with streptozotocin-induced diabetes (Group III, n=20), and rats with
      diabetes exposed to MF (Group IV, n=20). Muscle strips were taken from the distal
      tendon soleus and EDL muscles of rats killed by decapitation. The muscles were
      hung in organ baths containing Krebs solution (pH 7.4) with a gas mixture of 95%
      O2 and 5% CO2. Then the muscles were triggered to direct supramaximal stimulation
      with 0.05 Hz frequency square pulses for periods of 0.5 ms to obtain control
      values. The contractile parameters were also determined for two muscles of the
      four groups. Later, the tension-frequency relationship was determined by applying
      stimulating pulses of 10, 20, 50, and 100 Hz to the muscles. RESULTS: Diabetes
      caused a certain amount of decrease in the contractile force of the two muscles
      compared with that of control values. However, MF increased the contractile force
      of the two muscles in rats both with and without diabetes. The isometric
      contraction forces obtained by different stimulating frequencies showed a
      significant linear increase in the tetanic contraction (P<0.05). Diabetes
      increased the contraction time of the isometric twitch tension compared with that
      of the control group with a statistically significant difference (P<0.05). MF
      decreased the contraction time of the two muscles of rats without diabetes
      (P<0.05) but increased that of rats with diabetes (P>0.05). CONCLUSION: In our
      study, these results suggest that MF exposure regulates the isometric contractile
      characteristics of the soleus and EDL muscles of rats with diabetes, positively.

PMID- 18715204
TI  - Patient acceptance and issues of education of two durable insulin pen devices.
AB  - BACKGROUND: Insulin pen devices offer patients a more convenient, accurate, and
      discreet mode of insulin delivery than traditional syringes and vials. This open
      label, randomized, comparative crossover study assessed patient preference for
      two reusable pens: NovoPen 4 (Novo Nordisk A/S, Copenhagen, Denmark) and OptiClik
      (Sanofi-Aventis, Bridgewater NJ). METHODS: Thirty-five diabetes patients with no
      previous experience of pen devices (mean age 56.7 years; range 17-80 years; 57%
      male) used both pens to deliver a 10 unit saline dose into an injection cushion.
      Half received guidance according to official instruction manuals, and half were
      given no instructions. Learning times were also measured. Participants completed
      a detailed questionnaire to determine their preferences. RESULTS: Overall, 32 of
      35 participants preferred NovoPen 4 compared with two of 35 for OptiClik (91.4%
      vs. 5.7% respectively, P<0.001), and one had no preference. NovoPen 4 was
      significantly favored over OptiClik in almost all questionnaire criteria,
      including safety (P<0.001), size of pen (P<0.001), appearance (P<0.001), and ease
      of use (P<0.001). The majority of patients were able to use NovoPen 4 without
      guidance (94.4%) compared with just over half for for OptiClik (55.6%, P<0.01).
      Learning time was also significantly faster for NovoPen 4 (62.6 s) than for
      OptiClik (95.8 s) (P<0.05). CONCLUSIONS: Patients learned how to use both pens
      quickly (under 2 min), but NovoPen 4 was preferred by participants over OptiClik.
      Patient acceptance of a pen device may support insulin initiation, particularly
      in type 2 diabetes.

PMID- 18715205
TI  - Immunogenicity of human and bovine insulin in type 1 diabetes mellitus patients.
AB  - BACKGROUND: The advantages of synthetic insulin (human insulin) over bovine
      insulin in the treatment of type 1 diabetes mellitus (DM) are much debated in
      terms of potency and purity. Immunogenicity is one of several factors that
      determine potency and safety. This study was designed to investigate and study
      the difference in immunogenicity of human and bovine insulin. We investigated
      anti-insulin antibody (AIAB) status in 69 type 1 DM patients receiving insulin
      therapy. Group 1 had 33 patients treated with bovine insulin, and group 2 had 32
      patients treated with human insulin. All patients had received their respective
      insulin therapy for a minimum period of 1 year and had no history of change in
      insulin type. Forty-three subjects from the normal population were the control
      group. METHODS: AIABs were assayed in serum samples of all subjects using a
      semiquantitative radioimmunoassay kit. The Kruskal-Wallis non-parametric and Mann
      Whitney U tests were used to study the difference in immunogenicity of human and
      bovine insulins. RESULTS: The Kruskal-Wallis test showed that antibody titers in
      the three groups significantly differed (P<0.001). The Mann-Whitney U test showed
      no significant difference in AIAB titer between the treatment groups. AIAB titers
      in the two treatment groups differed significantly from that of the control
      group, independently (P<0.001). High titers of AIABs are present in patients
      receiving bovine and human insulin compared to that of the normal population.
      CONCLUSIONS: Bovine and human insulins are antigenic, and there is no significant
      difference in AIAB titer. Prospective studies are required to determine the long
      term clinical significance of these antibodies.

PMID- 18715207
TI  - Torcetrapib as potential treatment of low high-density lipoprotein cholesterol:
      no longer a pipe dream?

PMID- 18715206
TI  - Dosing accuracy with a novel pen device (SoloSTAR) as performed by patients with
      diabetes in a clinical setting.
AB  - BACKGROUND: Pen devices can help to overcome some of the barriers associated with
      insulin therapy. The present study evaluated the accuracy of dose delivery by
      people with diabetes using the novel prefilled, disposable SoloSTAR device with
      insulin glargine (Lantus) and insulin glulisine (Apidra) (all from sanofi
      aventis, Paris, France). METHODS: People with type 1 or type 2 diabetes (insulin
      users or insulin naive) were eligible to participate in this randomized, single
      center, open-label study. Each participant delivered six separate insulin doses
      into a sponge using SoloSTAR (three with glargine [10, 40, and 80 units] and
      three with glulisine [5, 15, and 30 units]). Pens were weighed before and after
      each test dose to determine the dose delivered. Thresholds for dosing accuracy
      were calculated according to the 2000 International Organization for
      Standardization (ISO) recommendations (Guideline 11608-1). RESULTS: All doses of
      glargine and glulisine delivered (60 participants; 360 individual doses) were
      within the ISO limits. Mean (standard deviation) glargine doses delivered were
      9.87 (0.24), 39.63 (0.36), and 79.02 (0.62) units for 10, 40, and 80 units,
      respectively. Insulin glulisine doses delivered were 4.98 (0.20), 14.87 (0.29),
      and 29.67 (0.34) units for 5, 15, and 30 units, respectively. CONCLUSIONS: The
      SoloSTAR pen allows people with diabetes to achieve a dosing accuracy with
      glargine and glulisine similar to that achieved in laboratory conditions. The
      dosing accuracy and ease of use of SoloSTAR may provide greater confidence in the
      precision and accuracy of the device while titrating glargine and/or glulisine to
      goal.

PMID- 18715208
TI  - Long-acting insulin analogs versus human insulins.

PMID- 18715209
TI  - Beyond the era of NPH insulin--long-acting insulin analogs: chemistry,
      comparative pharmacology, and clinical application.
AB  - The new rDNA and DNA-derived "basal" insulin analogs, glargine and detemir,
      represent significant advancement in the treatment of diabetes compared with
      conventional NPH insulin. This review describes blood glucose homeostasis by
      insulin in people without diabetes and outlines the physiological application of
      exogenous insulin in patients with type 1 and type 2 diabetes. The requirements
      for optimal basal insulin treatment are discussed and the methods used in the
      evaluation of basal insulins are presented. An essential criterion in the
      development of an "ideal" basal insulin preparation is that the molecular
      modifications made to the human insulin molecule do not compromise safety. It is
      also necessary to obtain a clear understanding of the pharmacokinetic and
      pharmacodynamic characteristics of the two currently available basal insulin
      analogs. When comparing glargine and detemir, the different molar concentration
      ratios of the two insulin formulations should be considered along with the
      nonspecificity of assay systems used to determine insulin concentrations.
      However, euglycemic clamp studies in crossover study design provide a good basis
      for comparing the pharmacodynamic responses. When the latter is analyzed by
      results of intervention clinical trials, it is concluded that both glargine and
      detemir are superior to NPH in type 1 and type 2 diabetes. However, there is
      sufficient evidence to demonstrate that these two long-acting insulin analogs are
      different in both their pharmacokinetic and pharmacodynamic profiles. These
      differences should be taken into consideration when the individual analogs are
      introduced to provide basal insulin supplementation to optimize blood glucose
      control in patients with type 1 and type 2 diabetes as well. PubMed-Medline was
      searched for articles relating to pharmacokinetics and pharmacodynamics of
      glargine and detemir. Articles retrieved were reviewed and selected for inclusion
      if (1) the euglycemic clamp method was used with a duration >or=24 h, (2) a
      single subcutaneous dose of glargine/detemir was used, and (3) area under the
      curve for insulin concentrations or glucose infusion rates were calculated.

PMID- 18715210
TI  - Validation of the SoloSTAR insulin pen.
AB  - BACKGROUND: This study was designed to validate the use of SoloSTAR (sanofi
      aventis Deutschland GmbH, Frankfurt, Germany), a new disposable pen developed for
      use with insulin glargine by patients with type 1 or type 2 diabetes. METHODS:
      This single-center, open-label, single-arm, sequential trial enrolled subjects
      with type 1 or type 2 diabetes, 21-78 years old. After face-to-face training
      (Part 1) or self-training (Part 2), subjects performed three dose-delivery
      repetitions into an injection pad using separate pens; pens were weighed before
      and after each dose delivery. The primary outcome was the proportion of subjects
      delivering successful doses (target dose, 40 units) with all three repetitions.
      Secondary outcomes included pen accuracy and precision. RESULTS: Validation
      population included 50 (Part 1) and 54 (Part 2) subjects. In Part 1, 100% of the
      subjects delivered a successful dose on all three repetitions. In Part 2, 98% of
      subjects delivered a successful dose on all three repetitions, with five cases of
      dose-delivery failures reported in the study population. The mean dose delivered
      was 40.2 units (95% confidence interval [CI], 40.1-40.3 units) in Part 1 and 38.0
      units (95% CI, 36.7-39.3 units) in Part 2; 99% and 88% of dose repetitions in
      Parts 1 and 2, respectively, were within 38-42 units. The safety test was
      successfully performed by 80% (95% CI, 70.2-88.0%) of subjects in Part 1 and 68%
      (95% CI, 58.1-77.6%) in Part 2. CONCLUSIONS: This study successfully validated
      the SoloSTAR pen for use by subjects with or without face-to-face training.
      SoloSTAR was shown to be easy to use, accurate, and precise.

PMID- 18715211
TI  - Dose accuracy comparison between SoloSTAR and FlexPen at three different dose
      levels.
AB  - BACKGROUND: The convenience and accuracy of insulin pens have led to their
      extensive use in patients with diabetes. Although all insulin pens go through
      extensive testing as part of the regulatory process, it is important that both
      the patient and clinician can be assured of the accuracy of the dose delivered.
      This study compared the dosing accuracy of two commonly available insulin pens,
      the SoloSTAR (sanofi-aventis Deutschland GmbH, Frankfurt, Germany) and FlexPen
      (Novo Nordisk A/S, Bagsvaerd, Denmark) devices. METHODS: Doses of 5, 10, and 30
      units of insulin were investigated for SoloSTAR and FlexPen, and specific units
      of accuracy were based on International Organization of Standards for insulin
      injection pens (+/-1 unit for the 5 and 10-unit doses, +/-5% for the 30-unit
      dose). A total of 30 pens were tested for both the SoloSTAR and FlexPen, and a
      total of 2,280 measurement values were taken for each pen type (5 units, 1,260;
      10 units, 750; and 30 units, 270 doses). RESULTS: Both devices were shown to be
      accurate at all three doses, and all doses were delivered within the limits
      proposed by the International Standard of Organization, which is used as part of
      the regulatory approval process when introducing an insulin injection device to
      the market. CONCLUSION: Our study shows that the SoloSTAR and FlexPen devices
      have comparable accuracy.

PMID- 18715212
TI  - Comparison of gliclazide with insulin as initial treatment modality in newly
      diagnosed type 2 diabetes.
AB  - AIM: This study was designed to compare effectiveness and remission rate between
      gliclazide and insulin as initial treatment in newly diagnosed, drug-naive
      patients with type 2 diabetes. METHODS: Newly diagnosed, drug-naive subjects with
      type 2 diabetes having mean fasting blood glucose >200 mg/dL were enrolled into
      either of two groups (gliclazide or insulin). The former received gliclazide
      modified-release 60 mg daily, while the insulin group received 16 units of
      premixed insulin as two divided doses along with medical nutrition therapy.
      Premeal blood glucose was monitored, and the dose was adjusted accordingly.
      Glycosylated hemoglobin (HbA1c), lipid profile, and postmeal C-peptide were
      estimated at baseline and 6 months. Remission was defined as euglycemia off drug
      for a minimum duration of 1 month. RESULTS: Baseline and 6-month blood glucose,
      HbA1c, and lipid profile were comparable between groups. Blood glucose levels
      normalized in 2-6 weeks in both groups. At 6 months, one of 30 (3.33%) in the
      gliclazide group and 24 of 30 (80%) in the insulin group were in remission. Ten
      of 16 (62.5%) in the insulin group and one of 20 (.5%) in the gliclazide group
      continued to maintain euglycemia off all pharmacological treatment at 12 months.
      At 6 months, C-peptide increased in the insulin group (3.21+/-1.61 ng/mL at
      baseline vs. 5.82+/-2.23 ng/mL at 6 months), while it remained unchanged in the
      gliclazide group (3.4+/-1.87 ng/mL at baseline vs. 3.82+/-1.78 ng/mL at 6 months)
      (P=0.0003). CONCLUSIONS: Comparable glycemic control could be achieved with both
      insulin and oral hypoglycemic agent in newly diagnosed type 2 diabetes subjects.
      Insulin treatment exceeded gliclazide in the remission (drug-free) rate.

PMID- 18715213
TI  - Improved glycemic control in intensively treated adult subjects with type 1
      diabetes using insulin guidance software.
AB  - BACKGROUND: Management of type 1 diabetes could be significantly improved with
      the availability of computerized insulin algorithms for home use. METHODS: This
      was a 1-year open label randomized control trial involving 123 adult subjects
      with type 1 diabetes (hemoglobin A1c values 7.5-11%) assigned to either the
      insulin guidance software (ACCU-CHEK) [Roche, Indianapolis, IN] Advisor) for
      personal data assistant (experimental group) or the control group. The primary
      aim of the study was to see if subjects using insulin dosing advisor software
      will improve glucose control over 1 year. The principal end point was an
      improvement in A1c at 6 and 12 months by >or=0.4%. RESULTS: Baseline demographics
      were similar in the two groups. Mean A1c was 8.54+/-0.11% in the control group
      and 8.42+/-0.11% (P=0.4265) in the experimental group. The mean A1c was
      significantly lower from 3 to 12 months in the experimental group (P<0.02). A1c
      reduction of >or=0.6% was maintained at 12 months in the experimental group.
      Also, a significantly higher number of subjects achieved A1c <7.5% in the
      experimental group from 3 to 9 months. Within target range glycemia (70-150
      mg/dL) was higher in the experimental group at 3-9 months without any change in
      insulin dose or weight. Above target range glycemia was lower in the experimental
      group throughout the study. Frequency of testing per day was higher in the
      experimental group. Nocturnal hypoglycemia was not different between groups;
      however, the experimental group experienced more severe hypoglycemic events.
      CONCLUSIONS: This is the first report that shows improved glycemic control can be
      maintained over 12 months in patients with type 1 diabetes by using Advisor with
      no change in insulin dose and weight.

PMID- 18715214
TI  - Sensor-augmented insulin pump therapy: results of the first randomized treat-to
      target study.
AB  - BACKGROUND: The objective of the study was to evaluate the clinical effectiveness
      and safety of a device that combines an insulin pump with real-time continuous
      glucose monitoring (CGM), compared to using an insulin pump with standard blood
      glucose monitoring systems. METHODS: This 6-month, randomized, multicenter, treat
      to-target study enrolled 146 subjects treated with continuous subcutaneous
      insulin infusion between the ages of 12 and 72 years with type 1 diabetes and
      initial A1C levels of >or=7.5%. Subjects were randomized to pump therapy with
      real-time CGM (sensor group [SG]) or to pump therapy and self-monitoring of blood
      glucose only (control group [CG]). Clinical effectiveness and safety were
      evaluated. RESULTS: A1C levels decreased (P<0.001) from baseline (8.44+/-0.70%)
      in both groups (SG, -0.71+/-0.71%; CG, -0.56+/-0.072%); however, between-group
      differences did not achieve significance. SG subjects showed no change in mean
      hypoglycemia area under the curve (AUC), whereas CG subjects showed an increase
      (P=0.001) in hypoglycemia AUC during the blinded periods of the study. The
      between-group difference in hypoglycemia AUC was significant (P<0.0002). Greater
      than 60% sensor utilization was associated with A1C reduction (P=0.0456).
      Fourteen severe hypoglycemic events occurred (11 in the SG group and three in the
      CG group, P=0.04). CONCLUSIONS: A1C reduction was no different between the two
      groups. Subjects in the CG group had increased hypoglycemia AUC and number of
      events during blinded CGM use; however, there was no increase in hypoglycemia AUC
      or number of events in the SG group. Subjects with greater sensor utilization
      showed a greater improvement in A1C levels.

PMID- 18715215
TI  - The accuracy and efficacy of real-time continuous glucose monitoring sensor in
      patients with type 1 diabetes.
AB  - BACKGROUND: The accuracy and efficacy of the Medtronic Diabetes (Northridge, CA)
      Real-Time (RT)-Continuous Glucose Monitoring (CGM) sensor were analyzed in 72
      subjects with type 1 diabetes. METHODS: This was a retrospective analysis of
      60,050 temporally paired data points (sensor and glucose meter values) obtained
      during the course of an outpatient ambulatory study evaluating the efficacy of a
      sensor-augmented pump system in adults and adolescents. Subjects uploaded sensor
      values and self-monitoring blood glucose data to the CareLink Clinical
      Application (Medtronic Diabetes) via the Internet, every 2 weeks during the
      course of the study. RESULTS: The overall percentage of sensor readings within +/
      20% or +/-30% agreement of reference glucose readings was 75.6% and 86.8%,
      respectively. The highest rate of agreement occurred in the 240-400 mg/dL range,
      where 79.9% of sensor readings were within +/-20% of meter values and 91.5% of
      sensor readings were within 30% of meter values. The mean absolute relative
      difference for all subjects was 15.8%, and the median absolute relative
      difference was 10.9%. The bias was -2.13 mg/dL. Paired glucose measurements from
      the RT-CGM and meter demonstrated that 95.9% of paired points in the overall
      subject population fell in zones A and B of the Clarke Error Grid. Consensus
      Error Grid Analysis established that 99.2% of paired data points were in zones A
      and B. CONCLUSIONS: This study reports the accuracy of a continuous glucose
      sensor with a large number of paired data points (60,050). RT-CGM is safe and
      well tolerated and provides readings that are in close agreement with glucose
      meter values.

PMID- 18715216
TI  - Pramlintide reduces the risks associated with glucose variability in type 1
      diabetes.
AB  - BACKGROUND: This study was designed to determine whether pramlintide added to
      insulin therapy reduced the risks associated with extreme blood glucose (BG)
      fluctuations in patients with type 1 diabetes. METHODS: Self-monitored BG (SMBG)
      records were retrospectively analyzed from a randomized, double-blind, placebo
      controlled study of the effects of pramlintide on intensively treated patients
      with type 1 diabetes. Two groups--pramlintide (n=119), 30/60 microg administered
      subcutaneously at each meal, or placebo (n=129)--were matched by age, gender, and
      baseline hemoglobin A1C. Using SMBG, daily BG profiles, BG rate of change, and
      low and high BG indices (LBGI and HBGI, respectively) measuring the risk for
      hypoglycemia and hyperglycemia were calculated. RESULTS: Compared with placebo,
      pramlintide significantly attenuated the pre- to postprandial BG rate of change
      (F=83.8, P<0.0001). Consequently, in pramlintide-treated patients, the average
      post-meal BG (8.4 vs. 9.7 mmol/L [151.2 vs. 174.6 mg/dL]) and postprandial HBGI
      were significantly lower than placebo (both P<0.0001). Substantial daily BG
      variation was observed in placebo-treated patients, with most significant
      hyperglycemia occurring after breakfast and during the night; post-meal BG did
      not vary significantly throughout the day in pramlintide-treated patients. The
      reduction in postprandial hyperglycemia in pramlintide-treated patients occurred
      without increased risk for preprandial hypoglycemia as quantified by the LBGI.
      CONCLUSIONS: Risk analysis of the effect of pramlintide treatment demonstrated
      risk-reduction effects independent of changes in average glycemia, most notably
      reduced rate and magnitude of postprandial BG fluctuations. These effects were
      not accompanied by an increased risk of hypoglycemia.

PMID- 18715217
TI  - Prevalence of albuminuria and cardiovascular risk profile in a referred cohort of
      patients with type 2 diabetes: an Asian perspective.
AB  - BACKGROUND: Microalbuminuria (MA) is a risk marker for diabetic nephropathy and
      cardiovascular (CV) disease (CVD) in patients with diabetes. This study aimed to
      describe the prevalence of albuminuria, CV risk factors, and treatments for renal
      and CV protection in an Asian population with type 2 diabetes. METHODS: This
      cross-sectional study conducted in eight Asian countries enrolled
      normotensive/hypertensive adults with type 2 diabetes without known proteinuria
      and/or non-diabetic kidney disease. Exclusion criteria were type 1 diabetes,
      menstruation, pregnancy, and acute fever. A single random urinary
      albumin/creatinine test was carried out in all patients. RESULTS: Of 8,561
      patients, 14% had diabetic retinopathy, and 17% and 21% had history of CV disease
      and smoking, respectively. Normoalbuminuria was seen in 44%, MA in 44%, and
      macroalbuminuria in 12%. Target glycosylated hemoglobin (HbA1c) (<7%) was reached
      in only 37% of 3,834 patients with available values. Diabetes was managed by diet
      alone in 6%, while others received oral hypoglycemic drugs and/or insulin. In
      total, 75% did not reach target blood pressure (BP) of <or=130/80 mm Hg.
      Antihypertensive drugs were prescribed to 52%, with the number of drugs
      increasing as the level of systolic BP increased. Drugs blocking the renin
      angiotensin system were most commonly prescribed, followed by calcium channel
      blockers. Lipid-lowering drugs and anticoagulant/antiplatelet agents were used in
      about 30% and 25% of patients, respectively. CONCLUSIONS: Asian patients with
      type 2 diabetes had a high prevalence of MA and reduced kidney function.
      Furthermore, BP and HbA1c control was only achieved in a minority of patients.
      Aggressive risk management by administration of reno- and cardioprotective
      treatments is urgently needed.

PMID- 18715218
TI  - Effects of chromium picolinate on food intake and satiety.
AB  - BACKGROUND: Chromium picolinate (CrPic) has been shown to attenuate weight gain,
      but the mechanism underlying this effect is unknown. METHODS: We assessed the
      effect of CrPic in modulating food intake in healthy, overweight, adult women who
      reported craving carbohydrates (Study 1) and performed confirmatory studies in
      Sprague-Dawley rats (Study 2). Study 1 utilized a double-blind placebo-controlled
      design and randomly assigned 42 overweight adult women with carbohydrate cravings
      to receive 1,000 mg of CrPic or placebo for 8 weeks. Food intake at breakfast,
      lunch, and dinner was directly measured at baseline, week 1, and week 8. For
      Study 2, Sprague-Dawley rats were fasted for 24 h and subsequently injected
      intraperitoneally with 0, 1, 10, or 50 microg/kg CrPic. Subsequently, rats were
      implanted with an indwelling third ventricular cannula. Following recovery, 0,
      0.4, 4, or 40 ng of CrPic was injected directly into the brain via the
      intracerebroventricular cannula, and spontaneous 24-h food intake was measured.
      RESULTS: Study 1 demonstrated that CrPic, as compared to placebo, reduced food
      intake (P<0.0001), hunger levels (P<0.05), and fat cravings (P<0.0001) and tended
      to decrease body weight (P=0.08). In study 2, intraperitoneal administration
      resulted in a subtle decrease in food intake at only the highest dose (P=0.03).
      However, when administered centrally, CrPic dose-dependently decreased food
      intake (P<0.05). CONCLUSIONS: These data suggest CrPic has a role in food intake
      regulation, which may be mediated by a direct effect on the brain.

PMID- 18715219
TI  - Role of emerging new technologies.

PMID- 18715220
TI  - Comments on evaluation of five glucose meters by Thomas et al.

PMID- 18715222
TI  - Proteomic identification of the silkworm (Bombyx mori L) prothoracic glands
      during the fifth instar stage.
AB  - Although the ecdysteroid of the silkworm had been studied for decades, the
      proteome of the prothoracic gland, the primary source of ecdysteroid hormones,
      has not been studied previously. In the present paper, we utilized a proteomic
      approach to investigate the fifth instar prothoracic gland during the growth and
      development of the silkworm, Bombyx mori L. The two-dimensional electrophoresis
      results showed that the majority of proteins were acidic proteins, especially
      concentrated in the area of 25-65 kDa, with pI values of between 4 and 7, and the
      difference was not distinct. When compared with Qiufeng (Japanese strain), the
      interspecific distinction was larger than the intraspecific distinction, and 19
      particular spots, excized from the third, fifth and ninth days of p50 (Chinese
      strain) and Qiufeng were subjected to MALDI-TOF-MS (matrix-assisted laser
      desorption ionization-time-of-flight MS) analysis. We sorted them into seven
      catagories: energetics and/or metabolism, storage proteins, protection, lipid
      metabolism, signal transduction, cell function and unknown function proteins. Of
      these proteins, arginine methyltransferase is discussed as playing an important
      role in regulating the activation of ecdysteroidogenesis via transcription or
      translation.

PMID- 18715227
TI  - Persistence and metabolic activity of Escherichia coli O157:H7 in farm animal
      faeces.
AB  - Ruminants, and to a lesser extent monogastric farm animals, are known to be
      natural reservoirs of Escherichia coli O157:H7, and contact with contaminated
      faeces has been linked to human infection. This study used a nontoxigenic,
      chromosomally marked, lux reporter strain to compare the persistence and activity
      (bioluminescence) of E. coli O157:H7 over 21 days in the faecal liquor of five
      farm animals: horse, sheep, cow, pig and piglet. Samples were inoculated with the
      lux E. coli O157:H7 (7.82 log CFU mL(-1)) and stored at 20 +/- 1 degrees C. The
      organism was recovered from all samples throughout the experimental period,
      although lower numbers were recovered from horse faecal liquor relative to all
      other types (P<0.001). The organisms' activity declined in all samples over time
      and no luminescence could be detected in any sample 21 days postinoculation.
      However, activity did increase greatly within pig and piglet faeces during
      initial stages of monitoring and overall luminescence was greater in piglet
      samples compared with all other samples (P<0.001). This is the first study to
      demonstrate how both the persistence and metabolic activity of E. coli O157:H7
      notably varies within a range of ruminant and nonruminant animal faeces. Further
      research is needed to elucidate the factors that govern differential persistence
      and metabolic activity of E. coli O157:H7 within such matrices.

PMID- 18715228
TI  - Sulphur isotopes and the search for life: strategies for identifying sulphur
      metabolisms in the rock record and beyond.
AB  - The search for life can only be as successful as our understanding of the tools
      we use to search for it. Here we present new sulphur isotope data (32S, 33S, 34S,
      36S) from a variety of modern marine environments and use these observations,
      along with previously published work, to contribute to this search. Specifically,
      we use these new data to gain a sense of life's influences on the sulphur isotope
      record and to distinguish these biologically influenced signatures from their non
      biological counterparts. This treatment extends sulphur isotope analyses beyond
      traditional (34S/32S) measures and employs trace isotope relationships (33S/32S,
      36S/32S), as the inclusion of these isotopes provides unique information about
      biology and its role in the sulphur cycle through time. In the current study we
      compare and contrast isotope effects produced by sulphur-utilizing microorganisms
      (experimental), modern and ancient sedimentary records (observational) and non
      biological reactions (theoretical). With our collective search for life now
      extending to neighbouring planets, we present this study as a first step towards
      more fully understanding the capability of the sulphur isotope system as a viable
      tool for life detection, both on Earth and beyond.

PMID- 18715229
TI  - Exploring QSARs for antiviral activity of 4-alkylamino-6-(2-hydroxyethyl)-2
      methylthiopyrimidines by support vector machine.
AB  - The support vector machine, which is a novel algorithm from the machine learning
      community, was used to develop quantitative structure activity relationship
      models to predict the antiviral activity of 4-alkylamino-6-(2-hydroxyethyl)-2
      methylthiopyrimidines. The genetic algorithm was employed to select the variables
      that resulted in the best-fitted models. A comparison between the obtained
      results using support vector machine with those of multiple linear regression
      revealed that support vector machine model was much better than multiple linear
      regression. The root mean square errors of the training set and the test set for
      support vector machine model were calculated to be 0.102 and 0.205, and the
      correlation coefficients (r2) were 0.956 and 0.852, respectively. Furthermore,
      the obtained statistical parameter of leave-one-out (LOO) and leave-group-out
      (LGO) cross-validation test on support vector machine model were 0.893 and 0.881,
      respectively, which prove the reliability of this model. The results suggest that
      branching, volume and lipophilicity are the main independent factors contributing
      to the antiviral activities of the studied compounds.

PMID- 18715230
TI  - Target-specific anti-fungal discovery by targeting Geotrichum candidum histidinol
      dehydrogenase: a hybrid approach.
AB  - This study describes a hybrid approach of screening substrate analogue inhibitors
      of histidinol dehydrogenase. Imidazole derivative library of approximately 400
      compounds classified using Hierarchical cluster analysis, representative
      compounds of each class were tested in enzymatic assay and used for the
      development of quantitative structure-activity relationship models. Rest of the
      compounds in the library were screened using developed models and compounds
      predicted active were retested. 60% of the predicted compounds showed enzyme
      inhibition activity with IC(50) values ranged between 5.2 and 58.0 microm range
      and have fungistatic activity.

PMID- 18715231
TI  - N-Fmoc-protected(alpha-dipeptidoyl)benzotriazoles for efficient solid-phase
      peptide synthesis by segment condensation.
AB  - N-Fmoc-protected(alpha-aminoacyl)benzotriazoles 1a-d readily afford chiral N-Fmoc
      protected-alpha-dipeptides 2a-f (77-89%). Compounds 2a-f are further converted
      into N-Fmoc-protected(alpha-dipeptidoyl)benzotriazoles 3a-f (71% average yield).
      Under mild microwave irradiation, 3a-f are used in solid-phase peptide segment
      condensation syntheses to give tri-, tetra-, penta-, hexa-, and heptapeptides (20
      68%).

PMID- 18715232
TI  - Reversible and competitive cinnamoyl triazole inhibitors of tissue
      transglutaminase.
AB  - A series of 15 cinnamoyl triazole derivatives was prepared by Cu(I)-catalyzed
      azide/alkyne [3+2]-cycloaddition reactions and examined as inhibitors of guinea
      pig liver transglutaminase. Several compounds exhibited activity as reversible
      inhibitors that were competitive with acyl donor transglutaminase substrates. For
      example, triazole 4d has a K(i) value of 174 nM and represents one of the most
      potent reversible transglutaminase inhibitors reported to date.

PMID- 18715233
TI  - Oncogenic BRAF(V600E) inhibits BIM expression to promote melanoma cell survival.
AB  - Somatic activating mutations of BRAF are the earliest and most common genetic
      abnormality detected in the genesis of human melanoma. However, the mechanism(s)
      by which activated BRAF promotes melanoma cell cycle progression and/or survival
      remain unclear. Here we demonstrate that expression of BIM, a pro-apoptotic
      member of the BCL-2 family, is inhibited by BRAF-->MEK-->ERK signaling in mouse
      and human melanocytes and in human melanoma cells. Trophic factor deprivation of
      melanocytes leads to elevated BIM expression. However, re-addition of trophic
      factors or activation of a conditional form of BRAF(V600E) leads to rapid
      inhibition of BIM expression. In both cases, inhibition of BIM expression was
      dependent on the activity of MEK1/2 and the proteasome. Consistent with these
      observations, pharmacological inhibition of BRAF(V600E) or MEK1/2 in human
      melanoma cells (using PLX4720 and CI-1040 respectively) led to a striking
      elevation of BIM expression. Re-activation of BRAF-->MEK-->ERK signaling led to
      phosphorylation of BIM-EL on serine 69 and its subsequent degradation.
      Interestingly, endogenous expression of BIM in melanoma cells was insufficient to
      induce apoptosis unless combined with serum deprivation. Under these
      circumstances, inhibition of BIM expression by RNA interference provided partial
      protection from apoptosis. These data suggest that regulation of BIM expression
      by BRAF-->MEK-->ERK signaling is one mechanism by which oncogenic BRAF(V600E) can
      influence the aberrant physiology of melanoma cells.

PMID- 18715234
TI  - Iris phenotypes and pigment dispersion caused by genes influencing pigmentation.
AB  - Spontaneous mutations altering mouse coat colors have been a classic resource for
      discovery of numerous molecular pathways. Although often overlooked, the mouse
      iris is also densely pigmented and easily observed, thus representing a similarly
      powerful opportunity for studying pigment cell biology. Here, we present an
      analysis of iris phenotypes among 16 mouse strains with mutations influencing
      melanosomes. Many of these strains exhibit biologically and medically relevant
      phenotypes, including pigment dispersion, a common feature of several human
      ocular diseases. Pigment dispersion was identified in several strains with mutant
      alleles known to influence melanosomes, including beige, light, and vitiligo.
      Pigment dispersion was also detected in the recently arising spontaneous coat
      color variant, nm2798. We have identified the nm2798 mutation as a missense
      mutation in the Dct gene, an identical re-occurrence of the slaty light mutation.
      These results suggest that dysregulated events of melanosomes can be potent
      contributors to the pigment dispersion phenotype. Combined, these findings
      illustrate the utility of studying iris phenotypes as a means of discovering new
      pathways, and re-linking old ones, to processes of pigmented cells in health and
      disease.

PMID- 18715235
TI  - Red 'Anjou' pear has a higher photoprotective capacity than green 'Anjou'.
AB  - Photoprotective function of anthocyanins along with xanthophyll cycle and
      antioxidant system in fruit peel was investigated in red 'Anjou' vs green 'Anjou'
      pear (Pyrus communis) during fruit development and in response to short-term
      exposure to high light. The sun-exposed peel of red 'Anjou' had higher maximum
      quantum yield of photosystem II (F(V)/F(M)) than that of green 'Anjou' and both
      the sun-exposed peel and the shaded peel of red 'Anjou' had smaller decreases in
      F(V)/F(M) after 2-h high light (photon flux density of 1500 mumol m(-2) s(-1))
      treatment than those of green 'Anjou'. At the middle and late developmental
      stages, the xanthophyll cycle pool size on a chlorophyll basis, the activity of
      superoxide dismutase, ascorbate peroxidase (APX), monodehydroascorbate reductase
      (MDAR), dehydroascorbate reductase (DHAR) and glutathione reductase (GR) and the
      level of reduced ascorbate and total ascorbate pool in the sun-exposed peel were
      either the same or lower in red 'Anjou' than in green 'Anjou', whereas the
      xanthophyll cycle pool size on a chlorophyll basis and the activity of APX,
      catalase, MDAR, DHAR and GR in the shaded peel were higher in red 'Anjou' than in
      green 'Anjou'. It is concluded that red 'Anjou' has a higher photoprotective
      capacity in both the sun-exposed peel and the shaded peel than green 'Anjou'.
      While the higher anthocyanin concentration along with the larger xanthophyll
      cycle pool size and the higher activity of some antioxidant enzymes may
      collectively contribute to the higher photoprotective capacity in the shaded peel
      of red 'Anjou', the higher photoprotective capacity in the sun-exposed peel of
      red 'Anjou' is mainly attributed to its higher anthocyanin concentration.

PMID- 18715236
TI  - Genistein induction of human sulfotransferases in HepG2 and Caco-2 cells.
AB  - Sulfotransferases are phase II drug-metabolizing enzymes. While the induction of
      sulfotransferases by hormones and endogenous molecules is relatively well known,
      induction by xenobiotics is not well studied. Isoflavones are naturally occurring
      phyto-oestrogens, mainly existing in soy food products. They have been described
      as health-promoting, disease-preventing dietary supplements and as agents with
      cancer-preventive activities. Recently, isoflavones have been reported to
      interact with nuclear receptors, including those that are known to mediate the
      induction of drug-metabolizing enzymes. In the present investigation, the
      isoflavone genistein was shown to be a xenobiotic inducer of human
      sulfotransferases in transformed human liver cells (HepG2) and colon carcinoma
      cells (Caco-2). Enzymatic activity assay, Western blot, and real-time reverse
      transcription-polymerase chain reaction (RT-PCR) results demonstrated that
      genistein significantly induced protein and mRNA expression of human simple
      phenol sulfotransferase (hSULT1A1) and human dehydroepiandrosterone
      sulfotransferase (hSULT2A1) in HepG2 and Caco-2 cells. The induction was time
      dependent and dose-dependent. Western blot results agreed well with real-time RT
      PCR results, suggesting that induction occurred at the gene transcription level.
      This isoflavone is the first nutritionally related phyto-oestrogen shown to
      induce human sulfotransferases in HepG2 and Caco-2 cells.

PMID- 18715237
TI  - Antioxidant effect of thiamine on acutely alcoholized rats and lack of efficacy
      using thiamine or glucose to reduce blood alcohol content.
AB  - Although there is no consensus about the use of glucose and thiamine for the
      treatment of acute ethanol intoxication, this is a routine practice in many
      countries. Our objective was to determine the efficacy of this treatment and the
      changes it causes in the antioxidant status of the liver. Male Wistar rats were
      intoxicated with an ethanol dose of 5 g/kg and divided into three groups: ethanol
      (EtOH; untreated), EtOH+G (treated with glucose), and EtOH+B1 (treated with
      thiamine). Blood and urinary ethanol as well as hepatic malondialdehyde, reduced
      glutathione and vitamin E were determined in all animals. Blood alcohol levels
      did not differ between groups, although urinary excretion was about four times
      higher in the group treated with thiamine (EtOH+B1). The malondialdehyde, reduced
      glutathione and vitamin E values used here as parameters of the antioxidant
      system of the liver showed improvement for the thiamine-treated group (EtOH+B1).
      Treatment with glucose or thiamine was ineffective in reducing blood alcohol
      levels in rats with acute ethanol intoxication. However, the beneficial effect of
      thiamine as an antioxidant for ethanol metabolism was demonstrated. Further
      investigations are necessary to clarify the urinary excretion of ethanol reported
      here for the first time and the possibility of using thiamine as an antioxidant
      in situations of chronic alcohol use.

PMID- 18715238
TI  - Mediators of a successful web-based smokeless tobacco cessation program.
AB  - AIM: To examine self-efficacy and program exposure as possible mediators observed
      treatment effects for a web-based tobacco cessation intervention. DESIGN: The
      ChewFree trial used a two-arm design to compare tobacco abstinence at both the 3-
      and 6-month follow-up for participants randomized to either an enhanced
      intervention condition or a basic information-only control condition. SETTING:
      Internet in US and Canada. PARTICIPANTS: Our secondary analyses focused upon 402
      participants who visited the web-based program at least once, whose baseline self
      efficacy rating showed room for improvement, who reported that they were still
      using tobacco at the 6-week assessment, and for whom both 3- and 6-month follow
      up data were available. INTERVENTION: An enhanced web-based behavioral smokeless
      tobacco cessation intervention delivered program content using text, interactive
      activities, testimonial videos and an ask-an-expert forum and a peer forum. The
      basic control condition delivered tobacco cessation content using static text
      only. MEASUREMENTS: Change in self-efficacy and program exposure from baseline to
      6 weeks were tested as simple and multiple mediators on the effect of treatment
      condition on point-prevalence tobacco abstinence measured at 3- and 6-month
      follow-up. FINDINGS: While both participant self-efficacy and program exposure
      satisfied the requirements for simple mediation, only self-efficacy emerged as a
      mediator when we used the more robust test of multiple mediation. CONCLUSIONS:
      Results confirm the importance of self-efficacy change as a probable underlying
      mechanism in a successful web-based behavioral intervention. While program
      exposure was found to be a simple mediator of tobacco abstinence, it failed to
      emerge as a mediator when tested with self-efficacy change in a multiple mediator
      test suggesting that self-efficacy and program exposure share a complex, possibly
      reciprocal relationship with the tobacco abstinence outcome. Our results
      underscore the utility of searching for mediators in research on web-based
      interventions.

PMID- 18715239
TI  - Endometriosis and its coexistence with irritable bowel syndrome and pelvic
      inflammatory disease: findings from a national case-control study--Part 2.
AB  - OBJECTIVE: To investigate whether the increased chances of having a diagnosis of
      irritable bowel syndrome (IBS) and pelvic inflammatory disease (PID) in women
      with endometriosis is due to misdiagnosis or co-morbidity. DESIGN: A case-control
      study of women aged 15-55 years with endometriosis and matched controls. SETTING:
      Data from the UK's General Practice Research Database for the years 1992-2001.
      SAMPLE: A total of 5540 women aged 15-55 years, diagnosed with endometriosis,
      each matched to four controls without endometriosis. The index date was defined
      as the date of diagnosis. METHODS: Data were analysed to determine whether women
      with endometriosis were more likely to receive a diagnosis of PIDor IBS than
      women without endometriosis. Odds ratios were calculated for endometriosis
      associated with IBS and PID before and after the index date. MAIN OUTCOME
      MEASURES: Diagnosis of IBS or PID before and after the index date. RESULTS:
      Compared with the controls, women with endometriosis were 3.5 times more likely
      to have received a diagnosis of IBS (OR 3.5 [95% CI: 3.1-3.9]). Even after women
      had been diagnosed with endometriosis, they were still two and a half times more
      likely to receive a new diagnosis of IBS when compared with the controls (OR 2.5
      [95% CI: 2.2-2.8]). Similarly, women with endometriosis were more likely than
      those without endometriosis to have been treated for PID both before (OR 5.9 [95%
      CI: 5.1-6.9]) and after (OR 3.8 [95% CI: 3.1-4.6]) being diagnosed with
      endometriosis. CONCLUSIONS: Women with endometriosis are more likely to be
      diagnosed with IBS and PID than controls, even after a definitive diagnosis of
      endometriosis has been reached.

PMID- 18715240
TI  - Can symptomatology help in the diagnosis of endometriosis? Findings from a
      national case-control study--Part 1.
AB  - OBJECTIVE: To determine the value of patient-reported symptoms in diagnosing
      endometriosis. DESIGN: A national case-control study. SETTING: Data from the UK
      General Practice Research Database for years 1992-2001. SAMPLE: A total of 5540
      women aged 15-55 years, diagnosed with endometriosis, each matched to four
      controls without endometriosis. METHODS: Data were analysed to determine whether
      specific symptoms were highly indicative of endometriosis. Odds ratios for these
      symptoms were derived by conditional logistic regression analysis. MAIN OUTCOME
      MEASURES: Symptoms associated with endometriosis. RESULTS: The prevalence of
      diagnosed endometriosis was 1.5%. A greater proportion of women with
      endometriosis had abdominopelvic pain, dysmenorrhoea or menorrhagia (73%)
      compared with controls (20%). Compared with controls, women with endometriosis
      had increased risks of abdominopelvic pain (OR 5.2 [95% CI: 4.7-5.7]),
      dysmenorrhoea (OR 8.1 [95% CI: 7.2-9.3]), menorrhagia (OR 4.0 [95% CI: 3.5-4.5]),
      subfertility (OR 8.2 [95% CI: 6.9-9.9]), dyspareunia and/or postcoital bleeding
      (OR 6.8 [95% CI: 5.7-8.2]), and ovarian cysts (OR 7.3 [95% CI: 5.7-9.4]), and of
      being diagnosed with irritable bowel syndrome (IBS) (OR 1.6 [95% CI: 1.3-1.8]) or
      pelvic inflammatory disease (OR 3.0 [95% CI: 2.5-3.6]). Women with endometriosis
      were also found to consult the doctor more frequently than the controls and were
      twice as likely to have time off work. CONCLUSIONS: Specific symptoms and
      frequent medical consultation are associated with endometriosis and appear useful
      in the diagnosis. Endometriosis may coexist with or be misdiagnosed as pelvic
      inflammatory disease or IBS.

PMID- 18715241
TI  - Non-hospital delivery and permanent congenital and early-onset hearing loss in a
      developing country.
AB  - OBJECTIVE: The objective of this study was to determine the role of non-hospital
      delivery and other risk factors for permanent congenital and early-onset hearing
      loss (PCEHL) in a developing country. DESIGN: Matched case-control study.
      SETTING: Four primary healthcare centres in inner-city Lagos, Nigeria.
      POPULATION: Fifty-six infants with PCEHL and 280 normal hearing controls matched
      for age and sex from a population of infants not older than 3 months attending
      Bacille de Calmette-Guerin immunisation clinics. METHODS: Conditional logistic
      regression analyses of infant and maternal characteristics associated with PCEHL,
      and the evaluation of population exposure to each risk factor. MAIN OUTCOME
      MEASURES: Adjusted matched odds ratios and population attributable risk percent
      (PAR%). RESULTS: Children with PCEHL were significantly more likely to be first
      born (OR 1.9, 95% CI 1.1-3.6) without skilled attendants at birth (OR 2.4, 95% CI
      1.3-4.5) and have a history of neonatal jaundice requiring exchange blood
      transfusion (NNJ/EBT) (OR 9.6, 95% CI 2.4-38.2) but less likely to be small for
      gestational age (SGA) (OR 0.1, 95% CI 0.0-0.5). After controlling for other
      covariates, the absence of skilled attendants at birth (OR 4.2, 95% CI 2.0-8.6)
      and NNJ/EBT (OR 19.1, 95% CI 4.3-85.5) emerged as predictors of PCEHL, while SGA
      (OR 0.1, 95% CI 0.0-0.2) retained its inverse relationship with PCEHL. The PAR%
      was 35.9% for the lack of skilled attendants at birth and 10.6% for having
      NNJ/EBT. About 23% of children with PCEHL did not exhibit any risk factors.
      CONCLUSIONS: NNJ/EBT and the absence of skilled attendant at birth rather than
      the place of delivery are significant predictors of PCEHL in this study
      population. Targeted hearing screening using these risk factors would facilitate
      the detection of about 77% of children with PCEHL.

PMID- 18715242
TI  - Antepartum bleeding of unknown origin in the second half of pregnancy and
      pregnancy outcomes.
AB  - OBJECTIVE: The purpose of our investigation was to evaluate factor(s) associated
      with unexplained antepartum bleeding of unknown origin (ABUO) after 24 weeks of
      pregnancy and correlate unexplained haemorrhage with maternal and perinatal
      outcomes. DESIGN: This is a retrospective observational study. SETTING: King
      Edward Memorial Hospital (KEMH), Subiaco, Western Australia. POPULATION:
      Singleton pregnancies delivering at KEMH between January 1998 and December 2004.
      METHODS: ABUO was defined as bleeding after 20 weeks of gestation but before the
      onset of labour with no cause detected on vaginal examination or abdominal
      ultrasound. Outcomes of these pregnancies were collated and compared with those
      of pregnancies without ABUO. MAIN OUTCOME MEASURES: Antepartum complications
      assessed included pre-eclampsia/eclampsia, gestational diabetes and preterm
      birth. Intrapartum evaluations included labour inductions, mode of delivery and
      gestational age at delivery. Neonatal outcomes evaluated included birthweight,
      Apgar scores, newborn intensive care unit (NICU) admission, neonatal
      complications and risk of perinatal/neonatal death. RESULTS: Between January 1998
      and December 2004, there were 26 583 deliveries without ABUO and 1431 with ABUO.
      Multivariable analyses of the ABUO effects revealed that ABUO was a
      simultaneously significant risk factor for term labour inductions (OR = 2.00, 95%
      CI: 1.72-2.32, P < 0.001), preterm delivery (OR = 4.31, 95% CI: 3.84-4.84, P <
      0.001), NICU admission (OR = 1.23, 95% CI: 1.01-1.51, P = 0.042),
      hyperbilirubinaemia (OR = 1.29, 95% CI: 1.01-1.63, P = 0.041) and reduced
      birthweight (26 g, 95% CI: 3-50, P = 0.026). CONCLUSION: Women with ABUO are at
      greater risk of preterm delivery, term labour induction and their neonates are at
      greater risk for NICU admissions, hyperbilirubinaemia and a reduced birthweight.

PMID- 18715243
TI  - Efficacy and safety of using mesh or grafts in surgery for anterior and/or
      posterior vaginal wall prolapse: systematic review and meta-analysis.
AB  - BACKGROUND: The efficacy and safety of mesh/graft in surgery for anterior or
      posterior pelvic organ prolapse is uncertain. OBJECTIVES: To systematically
      review the efficacy and safety of mesh/graft for anterior or posterior vaginal
      wall prolapse surgery. SEARCH STRATEGY: Electronic databases and conference
      proceedings were searched, experts and manufacturers contacted, and reference
      lists of retrieved papers scanned. SELECTION CRITERIA: Randomised controlled
      trials (RCTs), nonrandomised comparative studies, registries, case series
      involving at least 50 women, and RCTs published as conference abstracts from 2005
      onwards. DATA COLLECTION AND ANALYSIS: One reviewer screened titles/abstracts,
      undertook data extraction, and assessed study quality. Data analysis was
      conducted for three subgroups: anterior, posterior, and anterior and/or posterior
      repair (not reported separately). RESULTS: Forty-nine studies involving 4569
      women treated with mesh/graft were included. Study quality was generally high.
      Median follow up was 13 months (range 1-51 months). In anterior repair, there was
      short-term evidence that mesh/graft (any type) significantly reduced objective
      prolapse recurrence rates compared with no mesh/graft (relative risk 0.48, 95% CI
      0.32-0.72). Nonabsorbable synthetic mesh had a significantly lower objective
      prolapse recurrence rate (8.8%, 48/548) than absorbable synthetic mesh (23.1%,
      63/273) and biological graft (17.9%, 186/1041), but a higher erosion rate (10.2%,
      68/666) than absorbable synthetic mesh (0.7%, 1/147) and biological graft (6.0%,
      35/581). There was insufficient information to compare any of the other outcomes
      regardless of prolapse type. CONCLUSIONS: Evidence for most outcomes was too
      sparse to provide meaningful conclusions. Rigorous long-term RCTs are required to
      determine the comparative efficacy of using mesh/graft.

PMID- 18715244
TI  - A randomised controlled trial of intravaginal dinoprostone, intravaginal
      misoprostol and transcervical balloon catheter for labour induction.
AB  - OBJECTIVE: To compare the efficacy and safety of induction of labour by vaginal
      application of dinoprostone or misoprostol or transcervical insertion of a
      balloon (Bard) catheter. DESIGN: A non-blinded, randomised, controlled trial.
      SETTING: A tertiary level Swedish hospital. POPULATION: A total of 592 women who
      had undergone full-term pregnancies, not previously been subjected to a caesarean
      section, and required induction of labour for common, routine indications.
      METHODS: Women were randomly assigned to induction of labour using intravaginal
      dinoprostone (2 mg once every 6 hours) or misoprostol (25 micrograms once every 4
      hours) or a transcervical balloon catheter. MAIN OUTCOME MEASURES: The time
      interval between induction to delivery in general and vaginal delivery in
      particular, the mode of delivery, maternal and neonatal parameters of outcome.
      RESULTS: Of the 588 subjects included in the final intention-to-treat analysis,
      191 were assigned to treatment with dinoprostone, 199 with misoprostol and 198
      with the balloon catheter. The shortest mean induction-to-delivery interval was
      obtained with the catheter (12.9 hours versus 16.8 and 17.3 hours for
      dinoprostone and misoprostol, respectively). The efficacies of the two
      prostaglandins were similar. The maternal and neonatal outcomes associated with
      each of the three procedures were similar. CONCLUSIONS: Induction of labour with
      a transcervical balloon catheter is effective and safe and can be recommended as
      the first choice. The two prostaglandins, dinoprostone and misoprostol, were
      shown to be equally effective and safe, while misoprostol costs significantly
      less and is easier to store.

PMID- 18715245
TI  - Experiences and expectations of women with urogenital prolapse: a quantitative
      and qualitative exploration.
AB  - OBJECTIVE: To explore the expectations and goals of women undergoing surgery for
      urogenital prolapse using both a quantitative quality of life approach exploring
      symptom bother and a qualitative interview-based approach exploring patient goals
      and expectations. DESIGN: Prospective observational study. SETTING: Tertiary
      referral centre for urogynaecology. POPULATION: Forty-three women with
      symptomatic pelvic organ prolapse were recruited from the waiting list for pelvic
      floor reconstructive surgery. METHODS: All women were assessed with a structured
      clinical interview on an individual basis. The data obtained were transcribed
      verbatim and then analysed thematically based on the grounded theory. Individual
      codes and subcodes were identified to develop a coding framework. The prolapse
      quality-of-life (pQoL) questionnaire was used to determine the impact of pelvic
      organ prolapse on the woman's daily life. We arbitrarily classified 'bother' as
      minimal, mild, moderate and marked if scores ranged from 0 to 25, 25-50, 50-75
      and 75-100, respectively. The degree of prolapse was objectively quantified using
      the pelvic organ prolapse quantification (POP-Q) system. Quantitative data were
      analysed using SPSS. Ethical approval was obtained from the Kings College
      Hospital Ethics Committee. MAIN OUTCOME MEASURES: Quantitative data from POP-Q,
      subjective data from pQoL, qualitative data based on the structured clinical
      interview. RESULTS: Forty-three women were recruited over the first 1 year of the
      study. Their mean age was 56 years (range 36-78) and mean parity was 2 (range 0
      6). The mean ordinal stage of the prolapse was 2 (range stages 1-4). Quantitative
      analysis of the pQoL data suggested that the main domains affected were prolapse
      impact on life (mean score 74.71) and personal relationships (mean score 46.66).
      Qualitative analysis based on the clinical interview suggested that these women
      were most affected by the actual physical symptoms of prolapse (bulge, pain and
      bowel problems) as well by the impact prolapse has on their sexual function.
      CONCLUSIONS: While disease-specific QoL questionnaires allow broad comparisons to
      be made assessing patient bother, they may lack the sensitivity to assess
      individual symptoms. A qualitative approach may individualize patient care and
      ultimately improve patient satisfaction and overall outcome when treating women
      complaining of urogenital prolapse.

PMID- 18715246
TI  - The Prostate Cancer Prevention Trial and European Randomized Study of Screening
      for Prostate Cancer risk calculators indicating a positive prostate biopsy: a
      comparison.
AB  - OBJECTIVE: To assess the potential problem that different tools for predicting a
      positive outcome of prostate biopsy can produce divergent outcomes in the same
      man, by comparing the risk calculators based on the Prostate Cancer Prevention
      Trial (PCPT) and the European Randomized Study of Screening for Prostate Cancer
      (ERSPC). MATERIALS AND METHODS: In the prostate-specific antigen (PSA) range of
      0.2-30.0 ng/mL, the prediction curves of 'virtual' standard study participants
      were evaluated using both prediction tools. The effects of prostate volume,
      digital rectal examination, transrectal ultrasonography (TRUS), previous negative
      biopsy, family history, race, and age were also assessed. RESULTS: Important
      differences in underlying study design and populations between the PCPT and ERSPC
      cause an essential discrepancy between the risk calculators. In the PCPT there
      were few biopsies in the higher PSA ranges, and in the ERSPC in the lower PSA
      ranges. Both risk indicators have incorporated some variables that are not used
      in the other, because they were insignificant in multivariate analysis. TRUS and
      especially prostate volume (not available in the PCPT) have a considerably larger
      effect on predictions in comparable PSA ranges than race, age, family history of
      prostate cancer, and previous negative biopsy (indicators that were excluded in
      ERSPC). CONCLUSIONS: Before using risk calculators users must consider the
      properties of the underlying populations and what are the included or unavailable
      risk factors, and compare these to the patient. When these prerequisites are
      disregarded, dissimilarities will result in grossly inaccurate predictions for
      individual patients.

PMID- 18715247
TI  - Muscle-invasive bladder tumour: can the bladder be preserved?

PMID- 18715248
TI  - Comparisons of the responses of anterior and posterior human adult male bladder
      neck smooth muscle to in vitro stimulation.
AB  - OBJECTIVE: To evaluate differing methods of stimulation on strips of human
      bladder neck smooth muscle and compare muscle taken from the anterior and
      posterior aspects. MATERIALS AND METHODS: Samples of adult human male bladder
      neck muscle were obtained from patients undergoing open radical prostatectomy.
      Muscle was taken from either the anterior or posterior (nine and six patients,
      respectively) aspects of the bladder neck. Muscle strips dissected from these
      samples were suspended in the Brading-Sibley organ bath. The strips were
      superfused with 100 mm KCl-enriched Krebs' solution for 4 min to determine
      viability. This allowed experimentation on 17 strips from the anterior aspect of
      the bladder neck and 13 from the posterior bladder neck. These remaining strips
      were then superfused either with various concentrations (x10(-7) to x10(-3)m) of
      carbachol or noradrenaline in Krebs' solution, for 15 s. A further set of strips
      (eight from anterior, six from posterior) was suspended and responses to
      electrical field stimulation (EFS) with varying parameters were measured. Each
      EFS experiment was repeated after a 15 min exposure to 10(-3)m atropine, and
      again after a 15 min exposure 10(-7)m tetrodotoxin (TTX). Tension responses
      produced in these series of experiments were measured using strain gauges and
      analysed using data acquisition software. Student's t-test was used for the
      statistical analysis. RESULTS: All muscle strips included in the study responded
      to EFS. The magnitude of this contraction is frequency dependent. The
      contractions were abolished by superfusion of the muscle strips with atropine.
      There was no further suppression of the contractile response on addition of TTX.
      Posterior bladder neck samples had a greater mean contractile response per unit
      mass than anterior strips at all frequencies of >1 Hz, and significantly more at
      20 and 30 Hz. There was a concentration-dependent response in bladder neck
      contraction to carbachol but only in the strips from the anterior bladder neck at
      concentrations of <10(-3)m. Posterior bladder neck strips did not significantly
      contract upon application of carbachol. Similarly, there was a concentration
      dependent response to noradrenaline. Responses to noradrenaline were not uniform
      around the bladder neck, but not significantly different. Carbachol was the more
      'potent' stimulator in anterior smooth muscle strips, but again the differences
      between agonists were not statistically significant. CONCLUSION: These
      experiments show physiological variability around the circumference of the human
      male bladder neck. The posterior bladder neck shows significantly stronger
      contraction to alpha-adrenergic agonists compared with cholinergic agonists; the
      anterior bladder neck does not have a similarly significant differential
      response. The uniform response to noradrenaline may underlie the bladder neck's
      role in the prevention of retrograde ejaculation. The differential responses to
      carbachol may reflect differences in the embryological derivation of the anterior
      and posterior bladder neck fibres or in their innervation. Some of these
      differences may have clinical importance through the action of therapeutic
      agents.

PMID- 18715249
TI  - Is endoscopic-skills training in a skills laboratory necessary? Perceptions of
      urology programme directors in the Netherlands.

PMID- 18715250
TI  - A case of cutaneous nerve hypertrophy: association with multiple endocrine
      neoplasia type 2 or neurofibromatosis type 2?

PMID- 18715251
TI  - Effect of asiaticoside on hypertrophic scar in the rabbit ear model.
AB  - BACKGROUND: Previous observations suggested that asiaticoside had a possible
      antiscaring effect. However, the precise pathological mechanism still remain
      unknown. We questioned whether asiaticoside might alleviate the formation of
      hypertrophic scar by affecting the expression of Transform growth factor beta
      (TGF-beta)/Smad signaling. AIMS: To investigate the effect of asiaticoside on the
      expression of TGF-beta/Smad signaling in the rabbit ear model of hypertrophic
      scar and to clarify the mechanism of asiaticoside on the scar treatment. METHODS:
      The rabbit model with hypertrophic scar was created and applied topically with a
      low-dose (0.5%) or high-dose (1%) asiaticoside three times daily for 1, 2 or 3
      months and then we examined the changes of macroscopic and histopathologic
      characteristics of scars, and the expression of TGF-beta(1) and Smad protein was
      studied by applying reverse transcription-polymerase chain reaction and western
      blotting. RESULT: Asiaticoside could remarkably alleviate the scar in the rabbit
      ear model. Western blotting showed that the asiaticoside could decrease TGF
      beta(1) expression, and further study revealed that asiaticoside could remarkably
      enhance the expression of inhibitory Smad7, but it had no effect on the
      expression of Smad2. CONCLUSION: Asiaticoside suggested a possible antiscaring
      effect probably by enhancing the expression of inhibitive Smad7.

PMID- 18715252
TI  - Traumatic neuromas of the penis: a clinical, histopathological and
      immunohistochemical study of 17 cases.
AB  - We present 17 penile traumatic neuromas. The mean patient age at presentation was
      38 years (range 23-59 years). The most common site involved was the penile shaft.
      The lesions ranged from 1 to 7 mm in greatest dimension. The clinical diagnosis
      in all cases included condyloma acuminatum. In all cases, a history of trauma
      because of prior biopsy and/or circumcision was found. Histologically, all
      lesions showed similar features consisting of an increased number of dermal nerve
      bundles embedded within a fibrous stroma. Often, single or multiple Meissner
      corpuscle-like structures were noted in the papillary dermis. Our study suggests
      that circumcision or other forms of trauma to the skin of the penis likely plays
      an important role in the pathogenesis and clinical presentation of this peculiar
      neural neoplasm. We call attention to this entity because it is often clinically
      misdiagnosed as condyloma acuminatum.

PMID- 18715253
TI  - The histopathology of Phthirus pubis.

PMID- 18715254
TI  - Clinicopathological and immnuohistochemical findings in a series of
      folliculosebaceous cystic hamartoma.
AB  - BACKGROUND: Folliculo-sebaceous cystic hamartoma (FSCH) is an uncommon skin
      condition presenting as a slow-growing papulo-nodular lesion, in or around the
      nose. Most cases are not clinically suspected and only histopathological
      examination allows the diagnosis. Pathological features include a dermal-located
      infundibulo-cystic structure with sebaceous glands radiating around, a stromal
      component encircling the epithelial structures, with clefts between the lesional
      epithelial and stromal parts, as well as between this and the adjacent dermis.
      RESULTS: We report eight patients with the diagnosis of FSCH (5 females and 3
      males), with ages ranging from 35 to 77 years. Most cases (5 out of 8) were
      located in or around the nose and sizes were comprised between 0.6 and 1.2 cm.
      Lesions had grown for long periods of time, up to ten years in one case.
      Immunohistochemistry showed staining for p63 in the epithelial component of all
      lesions, while CD10 was only present in some sebocytes. CD34 and Factor XIIIa
      positive cells were present in the lesional stroma. Staining for androgen and
      alpha-estrogen receptors was also usually noticed. CONCLUSIONS: FCSH is a
      hamartomatous skin lesion, clinically indistinct but with well-defined
      histopathological features. Immunohistochemistry shows a profile very close to
      normal sebaceous glands.

PMID- 18715255
TI  - Anetodermic pilomatricoma.
AB  - A pilomatricoma, or Malherbe's calcifying epithelioma, is an uncommon tumor
      originating from hair matrix cells. It is clinically characterized by a solitary,
      firm nodule. As the skin overlying the pilomatricoma may change in color and
      texture, its clinical presentation can vary. We report an unusual case of
      pilomatricoma with associated anetoderma on the lower extremity of a 12-year-old
      girl. Histology revealed a thinned dermis replaced by myxomatous tissue between
      the surface and a deep-seated tumoral mass. This mass is formed of irregular
      islands of basaloid cells, shadow cells, calcified areas and discrete
      inflammatory and foreign-body reactions surrounding it. Anetodermic cutaneous
      changes may occur in pilomatricomas without histological evidence of triggering
      factors.

PMID- 18715256
TI  - Metastatic colorectal carcinoma: an unusual presentation.
AB  - Cutaneous metastases from colorectal carcinomas occur infrequently, usually in
      the setting of disseminated disease. They most commonly appear on the abdominal
      wall or perineal area; metastases to other locations of the skin are rare. We
      describe a case of colorectal signet ring carcinoma with metastasis to the upper
      lip. To the authors' knowledge, this is the second reported case of colorectal
      carcinoma with metastasis to the lip and first with signet ring features. Because
      of the rarity of cutaneous metastases, the primary physician or pathologist may
      overlook this diagnosis. However, this entity should be considered in the
      differential diagnosis of adnexal tumors as it may be the initial presentation of
      the colon carcinoma.

PMID- 18715257
TI  - Elevated frequency of p53 genetic mutations and AgNOR values in squamous cell
      carcinoma.
AB  - BACKGROUND: Epidermal squamous cell carcinoma (SCC) isa common malignancy in
      Pakistan. We hypothesize that it is characterized by higher frequency of p53
      genetic mutations and increased AgNOR values compared with squamous cell
      papilloma(SCP) and basal cell carcinoma (BCC). EXPERIMENTAL DESIGN: To test our
      hypothesis, 140 skin biopsies(including 20 normal skin, 20 SCP, 20 BCC and 80 SCC
      samples of various grades) were examined for p53 mutations using
      immunohistochemistry (IHC) and polymerase chain reaction (PCR). AgNOR staining
      was used for histological determination of AgNORindex. RESULTS: Both markers were
      undetectable in normal skin and were low in SCP. They were upregulated in BCC and
      SCC. PCR experiments revealed p53 mutations in 70% and 96.25% of BCC and SCC,
      respectively. Higher AgNOR values were seen in SCC than in BCC (mean AgNOR count
      = 5.81 +/- 31 and 8.36 +/- 19; percentage of AgNOR was 43.5% and 53% in BCC and
      SCC, respectively). Finally, p53 IHC score was found to be related to the AgNOR
      index in the histological grading of BCC and SCC (r = 10.983, p < 0.0001).
      CONCLUSION: Our results suggest that a higher frequency of p53 genetic mutations
      and increased AgNOR values exist in SCC compared with BCC and SCP. 'Consequently,
      SCC patients may have poorer prognosis'.

PMID- 18715258
TI  - To what extent does frontal type executive impairment affect coping strategies in
      Parkinson's disease?
AB  - BACKGROUND AND PURPOSE: Given the frequency of executive dysfunction in
      Parkinson's disease (PD), we wonder to what extent this fact might influence the
      coping strategies which are used. METHODS: A total of 135 PD patients with no
      dementia were divided into two groups according to their cognitive status ('with
      frontal type executive impairment' or 'without frontal type executive executive
      impairment'). All patients were seen for a semi-structured interview to collect
      sociodemographic and clinical information and to assess their cognitive and
      mental states (DSM-IV-TR, frontal assessment battery and Montgomery and Asberg
      Depression Rating Scale). Then, all patients completed two self-report
      questionnaires concerning their coping strategies (Ways of Coping Checklist and
      Coping with Health, Injuries and Problems Scale). RESULTS: After controlling the
      depression, we noticed a significant effect of cognitive status on positive re
      evaluation (P = 0.02). Interestingly, except for instrumental strategies,
      patients with frontal type executive impairment used significantly more coping
      strategies than did patients without frontal type executive impairment.
      CONCLUSION: Our results suggest that neither executive impairment nor depression
      prevents patients from using coping strategies extensively.

PMID- 18715259
TI  - Adapted Finnish Migraine-Specific Questionnaire for family studies (FMSQ(FS)): a
      validation study in two languages.
AB  - BACKGROUND AND PURPOSE: The hypothesis of a genetic component in the etiology of
      migraine is getting a foothold. However, to explore genetic associations,
      precision in clinical phenotypization is crucial. For this reason, migraine
      specific questionnaires, well discriminating between primary headaches, are
      required when large numbers of individuals need to be assessed. METHODS: We
      adapted and translated in two languages, German and Italian, the Finnish Migraine
      Specific Questionnaire for use in family studies. RESULTS AND CONCLUSIONS: This
      adaptation proved to be reliable when differentiating from primary headaches, and
      to be in very good agreement with the standard for comparison. However,
      discriminating between migraine with and without aura still relays on a
      specialist evaluation. This article describes the validation of this
      questionnaire.

PMID- 18715260
TI  - An assembly model for simulation of large-scale ground water flow and transport.
AB  - When managing large-scale ground water contamination problems, it is often
      necessary to model flow and transport using finely discretized domains--for
      instance (1) to simulate flow and transport near a contamination source area or
      in the area where a remediation technology is being implemented; (2) to account
      for small-scale heterogeneities; (3) to represent ground water-surface water
      interactions; or (4) some combination of these scenarios. A model with a large
      domain and fine-grid resolution will need extensive computing resources. In this
      work, a domain decomposition-based assembly model implemented in a parallel
      computing environment is developed, which will allow efficient simulation of
      large-scale ground water flow and transport problems using domain-wide grid
      refinement. The method employs common ground water flow (MODFLOW) and transport
      (RT3D) simulators, enabling the solution of almost all commonly encountered
      ground water flow and transport problems. The basic approach partitions a large
      model domain into any number of subdomains. Parallel processors are used to solve
      the model equations within each subdomain. Schwarz iteration is applied to match
      the flow solution at the subdomain boundaries. For the transport model, an
      extended numerical array is implemented to permit the exchange of dispersive and
      advective flux information across subdomain boundaries. The model is verified
      using a conventional single-domain model. Model simulations demonstrate that the
      proposed model operated in a parallel computing environment can result in
      considerable savings in computer run times (between 50% and 80%) compared with
      conventional modeling approaches and may be used to simulate grid discretizations
      that were formerly intractable.

PMID- 18715261
TI  - Robust representation of dry cells in single-layer MODFLOW models.
AB  - Dewatered or "dry" grid cells in the USGS ground water modeling software MODFLOW
      may cause nonphysical artifacts, trigger convergence failures, or interfere with
      parameter estimation. These difficulties can be avoided in two dimensions by
      modifying the spatial differencing scheme and the iterative procedure used to
      resolve nonlinearities. Specifically, the spatial differencing scheme is modified
      to use the water level on the upstream side of a pair of adjacent cells to
      calculate the saturated thickness and hence intercell conductance for the pair.
      This makes it possible to explicitly constrain the water level in a cell to be at
      or above the cell bottom elevation without introducing nonphysical artifacts.
      Thus constrained, all initially active cells will remain active throughout the
      simulation. It was necessary to replace MODFLOW's Picard iteration method with
      the Newton-Raphson method to achieve convergence in demanding applications
      involving many dry cells. Tests using a MODFLOW variant based on the new method
      produced results nearly identical to conventional MODFLOW in situations where
      conventional MODFLOW converges. The new method is extremely robust and converged
      in scenarios where conventional MODFLOW failed to converge, such as when almost
      all cells dewatered. An example application to the Edwards Aquifer in south
      central Texas further demonstrates the utility of the new method.

PMID- 18715262
TI  - Modeling interaction of fluid and salt in an aquifer/lagoon system.
AB  - To simulate the dynamic interaction between a saline lagoon and a ground water
      system, a numerical model for two-dimensional, variable-density, saturated
      unsaturated, and coupled flow and solute transport (saltwater intrusion by finite
      elements and characteristics [SIFEC]) was modified to allow the volume of water
      and mass of salt in the lagoon to vary with each time step. The modified SIFEC
      allows the stage of a lagoon to vary in accordance with a functional relation
      between the stage and water volume of the lagoon, and also allows the salt
      concentration of the lagoon to vary in accordance with the salt budget of the
      lagoon including chemical precipitation and dissolution of salt. The updated
      stage and salt concentration of the lagoon are in turn used as transient boundary
      conditions for the coupled flow and solute transport model. The utility of the
      modified model was demonstrated by applying it to the eastern Mediterranean
      coastal region of Turkey for assessing impacts of climate change on the
      subsurface environment under scenarios of sea level rise, increased evaporation,
      and decreased precipitation.

PMID- 18715263
TI  - A watershed in our profession.

PMID- 18715264
TI  - Dissecting the role of  Kr-h1   brain gene expression in   foraging behavior in
      honey bees (Apis mellifera).
AB  - Expression of Kruppel homolog-1 (Kr-h1) in the honey bee brain is strongly
      associated with foraging behavior. We performed a series of studies to determine
      if Kr-h1 expression correlates with specific aspects of foraging. We found that
      Kr-h1 expression is unaffected by flight experience in male bees. Expression was
      unaffected by behavioral reversion of workers from foraging to brood care,
      suggesting that expression is not associated with the active performance of
      foraging, but rather with stable physiological changes. Kr-h1 expression is
      increased by cGMP treatment in workers, and the Kr-h1 promoter contains a
      conserved potential cGMP response element. Since cGMP treatment causes precocious
      foraging, our results suggest that Kr-h1 expression is associated with cGMP
      mediated changes in the brain that occur early in the transition to foraging
      behavior.

PMID- 18715265
TI  - MsSOCS  expression indicates a potential role for   JAK/STAT signalling in the
      early stages of   Manduca   sexta   spermatogenesis.
AB  - Our understanding of the Drosophila melanogaster testis stem cell niche has
      identified the signalling pathways required to maintain stem cells and promote
      self-renewal. Here we present the first detailed examination of the testes stem
      cell niche in the lepidopteran Manduca sexta . We show that larval testes contain
      hub-like structures surrounded by mitotically active cells likely to represent a
      self-renewing stem cell population. In addition, we have cloned DNA fragments
      encoding parts of M. sexta Signal Transducer and Activators of Transcription
      (STAT) and Suppressor of Cytokine Signalling (SOCS) homologues and show that
      expression of MsSOCS is upregulated in hub-adjacent cells. Given the conservation
      of socs-like genes and their regulation as Janus Kinases/Signal Transducer and
      Activators Transcription (JAK/STAT) pathway targets, we suggest that increased
      expression within the testis stem cells indicates increased levels of JAK/STAT
      signalling and a conserved role for pathway signalling in testis stem cell
      maintenance.

PMID- 18715266
TI  - Development of a Chinese-Indian hybrid (Chindian) rhesus macaque colony at the
      California National Primate Research Center by introgression.
AB  - BACKGROUND: Fullbred Chinese and Indian rhesus macaques represent genetically
      distinct populations. The California National Primate Research Center introduced
      Chinese founders into its Indian-derived rhesus colony in response to the 1978
      Indian embargo on exportation of animals for research and the concern that loss
      of genetic variation in the closed colony would hamper research efforts. The
      resulting hybrid rhesus now number well over a thousand animals and represent a
      growing proportion of the animals in the colony. METHODS: We characterized the
      population genetic structure of the hybrid colony and compared it with that of
      their pure Indian and Chinese progenitors. RESULTS: The hybrid population
      contains higher genetic diversity and linkage disequilibrium than their full
      Indian progenitors and represents a resource with unique research applications.
      CONCLUSIONS: The genetic diversity of the hybrids indicates that the strategy to
      introduce novel genes into the colony by hybridizing Chinese founders and their
      hybrid offspring with Indian-derived animals was successful.

PMID- 18715267
TI  - Primary hepatic neuroendocrine carcinoma in a baboon (Papio sp.).
AB  - BACKGROUND: Primary neuroendocrine carcinomas of the liver have rarely been
      reported in humans and domestic animals, but not in non-human primates. METHODS:
      We describe the morphologic and immunohistochemical features of a primary hepatic
      neuroendocrine carcinoma found in a 29-year-old female baboon. RESULTS AND
      CONCLUSIONS: The neoplasm was characterized by multiple solid nodules that were
      multifocally distributed in the liver. Metastases were not observed.
      Histologically, the neoplasm was composed of cords and nests of epithelial cells
      arranged in a neuroendocrine pattern, occasionally forming glandular and rosette
      like structures. On immunohistochemical evaluation, the neoplastic cells were
      immunopositive for pancytokeratin, chromogranin A, neuron-specific endolase, and
      synaptophysin and were negative for vimentin, S100 protein, glucagon, and
      insulin.

PMID- 18715268
TI  - Guidelines for the prevention and control of tuberculosis in non-human primates:
      recommendations of the European Primate Veterinary Association Working Group on
      Tuberculosis.
AB  - BACKGROUND: Effective tuberculosis (TB) control requires accurate diagnostic
      methods but the tuberculin skin test has serious limitations. Both false-negative
      and false-positive reactions are common, resulting in the spread of the infection
      and devastating TB outbreaks. Results of questionnaire surveys concerning TB
      testing practices in primate housing facilities showed great differences in
      testing practices. Although there was some uniformity regarding the sites of
      application, the amounts of tuberculin used and the time intervals for retesting,
      a great deal of variety was revealed considering the types of tuberculin
      preparations, the interpretation of tests and the susceptibility of animals.
      CONCLUSION: Here, we summarize the most common practices as regards TB control
      and prevention for non-human primates, and attempt to establish a uniform
      guideline based upon our experience with primate husbandry and care programmes as
      well as recent developments in the literature. The present guideline represents a
      consensus recommendation intending to harmonize the existing protocols.

PMID- 18715269
TI  - Neurofilament tail phosphorylation: identity of the RT-97 phosphoepitope and
      regulation in neurons by cross-talk among proline-directed kinases.
AB  - As axons myelinate, establish a stable neurofilament network, and expand in
      caliber, neurofilament proteins are extensively phosphorylated along their C
      terminal tails, which is recognized by the monoclonal antibody, RT-97. Here, we
      demonstrate in vivo that RT-97 immunoreactivity (IR) is generated by
      phosphorylation at KSPXK or KSPXXXK motifs and requires flanking lysines at
      specific positions. extracellular signal regulated kinase 1,2 (ERK1,2) and
      pERK1,2 levels increase in parallel with phosphorylation at the RT-97 epitope
      during early postnatal brain development. Purified ERK1,2 generated RT-97 on both
      KSP motifs on recombinant NF-H tail domain proteins, while cdk5 phosphorylated
      only KSPXK motifs. RT-97 epitope generation in primary hippocampal neurons was
      regulated by extensive cross-talk among ERK1,2, c-Jun N-terminal kinase 1,2
      (JNK1,2) and cdk5. Inhibition of both ERK1,2 and JNK1,2 completely blocked RT-97
      generation. Cdk5 influenced RT-97 generation indirectly by modulating JNK
      activation. In mice, cdk5 gene deletion did not significantly alter RT-97 IR or
      ERK1,2 and JNK activation. In mice lacking the cdk5 activator P35, the partial
      suppression of cdk5 activity increased RT-97 IR by activating ERK1,2. Thus, cdk5
      influences RT-97 epitope generation partly by modulating ERKs and JNKs, which are
      the two principal kinases regulating neurofilament phosphorylation. The
      regulation of a single target by multiple protein kinases underscores the
      importance of monitoring other relevant kinases when the activity of a particular
      one is blocked.

PMID- 18715270
TI  - Melatonin inhibits arsenite-induced peripheral neurotoxicity.
AB  - In this study, the effect of melatonin on sodium arsenite (arsenite)-induced
      peripheral neurotoxicity was investigated using dorsal root ganglion (DRG)
      explants. After 24-hr incubation, arsenite (30 microm) consistently elevated the
      expression of heat shock protein 70 and haeme oxygenase-1, two well-known stress
      proteins, in the treated DRG explants. Co-incubation with melatonin (4 and 20 mm)
      concentration-dependently attenuated arsenite-induced elevation in stress
      proteins. Furthermore, melatonin inhibited arsenite-induced phosphorylation of
      p38 and DNA fragmentation. Inhibition by melatonin of arsenite-induced apoptosis
      was mediated via inactivating both endoplasmic reticulum (ER) and mitochondrial
      pathways. In the ER pathway, melatonin suppressed arsenite-induced elevation in
      activating transcription factor-6 and CCAAT/enhancer-binding protein homologous
      protein in the nuclear fraction of the treated DRG explants. Moreover, melatonin
      attenuated arsenite-induced activation of caspase 12, an ER-specific enzyme. In
      the mitochondrial pathway, arsenite-induced increases in Bcl-2 levels and
      cytosolic cytochrome c were reduced by melatonin. At the same time, melatonin
      inhibited arsenite-induced activation of caspase 3 in the treated DRG explants.
      Compared with glutathione and N-acetyl cysteine, melatonin was more potent than
      either in inhibiting arsenite-induced elevation in stress proteins. Taken
      together, our study demonstrates that melatonin is protective against arsenite
      induced neurotoxicity in DRG explants. In addition, melatonin prevented arsenite
      induced apoptosis via suppression of ER and mitochondrial activation. Our data
      suggest that melatonin is potentially a therapy for arsenite-induced peripheral
      neuropathy.

PMID- 18715271
TI  - Frontotemporal lobar degeneration with ubiquitinated tau-negative inclusions and
      additional alpha-synuclein pathology but also unusual cerebellar ubiquitinated
      p62-positive, TDP-43-negative inclusions.
AB  - Mutations in the progranulin (PGRN) gene on chromosome 17 have been shown to be
      responsible for one non-tauopathy subtype of familial frontotemporal lobar
      degeneration - frontotemporal lobar degeneration with ubiquitinated, tau-negative
      inclusions (FTLD-U). Such cases have pathological similarities to sporadic cases
      with neuronal inclusions positive for ubiquitin, the ubiquitin binding protein,
      p62 and the newly recognised protein TDP-43 but negative for hyperphosphorylated
      (HP) tau. There has been a recent report on two families with a novel progranulin
      mutation where the neuropathology showed not only TDP-43 neuronal positivity but
      separate tau and/or alpha-synuclein pathology. We describe an unusual case with
      some family history but no mutation in the progranulin gene. The pathological
      features were typical for FTLD-U but with additional significant alpha-synuclein
      pathology, and unusual ubiquitin-positive, p62-positive, TDP-43-negative
      inclusions in the cerebellum. This case may represent a further pathological
      phenotype for familial FTLD-U. It also highlights the need for further
      investigations on the ubiquitin binding protein p62 as a marker in FTLD-U. It is
      certainly possible that the presence or absence of these ubiquitinated p62
      positive yet TDP-43-negative cerebellar inclusions may act as a useful
      correlative factor in the future.

PMID- 18715272
TI  - Coexistence of Creutzfeldt-Jakob disease, Lewy body disease, and Alzheimer's
      disease pathology: an autopsy case showing typical clinical features of
      Creutzfeldt-Jakob disease.
AB  - We report here an autopsy case of sporadic Creutzfeldt-Jakob disease (CJD)
      without hereditary burden and with a clinical course typical of sporadic CJD. A
      77-year old man developed memory disturbance, followed by gait disturbance and
      myoclonus. He died of bronchopneumonia 5 months after the disease onset. Post
      mortem examination revealed neuronal loss, astrocytosis, and patchy spongiosis in
      the cerebral cortex and lenticular nuclei. Synaptic-type deposits of prion
      protein were present in the cerebral cortex. Additionally, Lewy bodies were
      observed in the cerebral cortex and substantia nigra. Furthermore, senile plaques
      compatible with definite Alzheimer's disease according to Consortium to Establish
      a Registry for Alzheimer's disease criteria and neurofibrillary changes of the
      limbic system consistent with Braak stage IV were found. Based on a review of the
      published literature, this autopsy case is very rare, and we suppose that the
      incidence of CJD accompanied by Lewy body disease and Alzheimer's disease is very
      low.

PMID- 18715273
TI  - Multiple neuroenteric cysts at cerebello-pontine angle and foramen magnum: a case
      report and review of the literature.
AB  - Neuroenteric cysts of the CNS are uncommon benign lesions usually involving the
      spinal cord or rarely the cerebellopontine angle (CPA). We report a rare example
      of multiple neuroenteric cysts arising from the CPA and foramen magnum in a 20
      year-old Caucasian woman who presented with headaches and dizziness. An MRI
      showed three separate lesions, not communicating with each other. The first
      lesion, within the left posterior lateral aspect of the CPA, demonstrated
      isointensity to gray matter on the fluid-attenuated inversion recovery (FLAIR)
      sequence. The second lesion, within the left foramen of Luschka at the level of
      the CPA, demonstrated hyperintensity on the T(2)-weighted sequences, intermediate
      to slightly hyperintense on T(1)-weighted sequence and hyperintensity on FLAIR.
      The third lesion, within the anterior/inferior left cerebellum at the level of
      the foramen magnum, followed CSF signal intensity throughout. None of the lesions
      demonstrated significant enhancement or bone lesions. Due to compression effect,
      surgery was performed. Pathologic examination revealed cystic structures lined by
      a single layer of non-ciliated well-differentiated mucin-producing columnar
      epithelium with eosinophilic to amphophilic cytoplasm and round to oval nuclei
      with focal pseudostratification. Immunohistochemical studies showed focal
      positivity for cytokeratin 7, CK 5/6, synaptophysin, and carcinoembryonic antigen
      (CEA), diffuse positive staining for epithelial membrane antigen (EMA) and
      BerEP4; and negative staining for cytokeratin 20, TTF-1, and GFAP. The MIB-1
      proliferation index was < 1%. One-year follow-up has shown no recurrence. The
      differential diagnosis and a brief review of the literature are also presented.

PMID- 18715274
TI  - Biphasic effects of moderate drinking on prolactin during lactation.
AB  - BACKGROUND: Contrary to the popular lore that encourages women to drink alcohol
      as an aid to lactation, we previously showed that alcohol consumption disrupted
      lactational performance and the hormonal milieu of the lactating mother in the
      short term. METHODS: Thirteen lactating women participated in a 4-session, double
      blind, 2 x 2 within-subject study to test several hypotheses related to the
      effects of alcohol on prolactin (PRL) responses and milk yield over time. The two
      within-subject factors were beverage condition (control or 0.4 g/kg dose of
      alcohol) and pumping condition (pumping occurred at fixed intervals once or twice
      during the 5.3-hour session). Plasma PRL, blood alcohol concentrations (BAC), and
      milk yield were measured. RESULTS: Alcohol consumption increased basal PRL levels
      (p < 0.0001) and modified the PRL response to pumping (p < 0.0001) but the
      directionality of the response depended on when pumping occurred along the BAC
      curve. Pumping enhanced PRL response when it occurred during the ascending BAC
      limb but blunted the response when it occurred during the descending limb,
      providing evidence that the effects were transient and of a biphasic nature. The
      slower the alcohol was metabolized, the greater the relative PRL response to
      breast pumping (p < 0.05). The dynamics of the PRL response between pumping
      sessions was also altered if women drank. If women pumped within the hour after
      drinking alcohol, the PRL response during the next pumping some 1.5 hours later,
      was delayed by a few minutes. Milk yield was significantly lower after drinking
      alcohol but such deficits were not significantly related to PRL or the speed at
      which alcohol was eliminated. CONCLUSIONS: Effects of alcohol on suckling-induced
      PRL were biphasic in nature, but could not explain the deficits in lactational
      performance. Such findings provide further evidence that the dynamic changes in
      neuroendocrine state are integrally involved in alcohol's effects over time and
      underscore the complexity of lactation.

PMID- 18715275
TI  - Effects of functional polymorphisms related to catecholaminergic systems on
      changes in blood catecholamine and cardiovascular measures after alcohol
      ingestion in the Japanese population.
AB  - BACKGROUND: The polymorphism of human aldehyde dehyrogenase-2 (ALDH2) Glu(487)Lys
      is well known to be a crucial factor underlying the genetic background for
      alcohol sensitivity in Asian populations. Subjects with the inactive Lys(487)
      allele show a marked increase in blood acetaldehyde level after alcohol intake,
      which results in facial flushing and various cardiovascular-related symptoms.
      However, other polymorphisms related to catecholaminergic systems that tightly
      regulate the activity of the sympathetic nervous system may also influence the
      physiological changes after acute alcohol intake. METHODS: We investigated
      whether, together with the ALDH2 Gly(487)Lys and ADH1B Arg(47)His genotype,
      putative functionally important polymorphisms, including 9 loci in 7 human genes,
      were associated with changes in blood catecholamine levels and cardiovascular
      measures after alcohol ingestion. Forty-nine young Japanese males were subjected
      to blood catecholamine analysis after alcohol ingestion. Among them, 28 were also
      subjected to heart rate variability and blood pressure analysis. The contribution
      of polymorphisms to the alcohol-induced response was analyzed by multiple
      regression analysis. RESULTS: Among the polymorphisms examined in this study,
      haplotypes of the phenylethanolamine N-methyltransferase (PNMT) promoter [(
      182bpG/A)_(-387bpG/A)] and catechol-O-methyltransferase (COMT) exon 4 [(Ex4 +
      119bpC/G)_(Ex4 + 138bpG/A), Leu(136)Leu_Val(158)Met] are suggested to have
      functionally important effects on alcohol-induced cardiovascular symptoms by
      affecting blood catecholamine levels. The neuropeptide Y (NPY) promoter C-1450T
      genotype is also suggested to be involved in the individual differences in
      regulation of catecholamine secretion. CONCLUSIONS: This study suggested that
      these common polymorphisms of genes related to catecholaminergic systems, as well
      as those of the alcohol metabolizing system, are significant for understanding
      the basis of individual differences in alcohol sensitivity.

PMID- 18715276
TI  - Incidence of cardiovascular and cerebrovascular disease in Danish men and women
      with a prolonged heavy alcohol intake.
AB  - BACKGROUND: Several epidemiological studies have found U- or J-shaped
      relationships between alcohol intake and cardiovascular conditions. The influence
      of heavy drinking is, however, sparsely studied. The objective of the present
      study was to examine whether alcohol addicts have higher incidence rates of
      cardio- and cerebrovascular diseases than the population in general. METHODS: The
      cohort comprised 19,185 subjects (15,368 men and 3,817 women) who attended
      outpatient clinics for alcohol abusers within the Copenhagen Hospital Corporation
      (1954 to 1992). Incidence rates were standardized (SIR) according to sex, age and
      calendar time to compare subjects' cardio- and cerebrovascular incidence with
      that of the general population of Copenhagen. RESULTS: During the period 1977 to
      2001 a total of 9,397 events of cardio- and cerebrovascular disease were
      observed. In both men and women, statistically significant higher incidence rates
      than would be expected in a standard population were observed for cardiovascular
      diseases (e.g., ischemic heart diseases, men: SIR = 1.76; 95% CI 1.69-1.83;
      women: SIR = 2.44; 95% CI 2.19-2.73) and cerebrovascular diseases (e.g.,
      hemorrhagic stroke, men: SIR = 2.71; 95% CI 2.45-2.99; women: SIR = 2.77; 95% CI
      2.18-3.48). CONCLUSIONS: The study indicates increased risks of cardio- and
      cerebrovascular diseases in subjects with an excessive alcohol intake.

PMID- 18715277
TI  - Neuropsychological characteristics of Italian children with fetal alcohol
      spectrum disorders.
AB  - BACKGROUND: Children with fetal alcohol spectrum disorders (FASD) display many
      problems ranging from deficits in intelligence to behavioral difficulties. Thus,
      many studies have aimed at defining the neuropsychological characteristics of
      children with FASD. The current article describes the neuropsychological
      characteristics of Italian children with severe diagnosis within FASD and
      compares them with controls. It was expected that intellectual functioning,
      language comprehension, academic skills, and inattention/hyperactivity would
      discriminate children with FASD from randomly selected peers without FASD.
      METHODS: This article presents data from a second cohort of children examined in
      2005 as part of an in-school epidemiological study of FASD in Italy. Of 80
      children, 23 diagnosed with a FASD, and 57 randomly selected control children
      from the same first-grade classes, participated. After screening for FASD via
      growth and dysmorphology, the children were administered a test of general
      intelligence (WISC-R) as well as tests of nonverbal reasoning (Raven Colored
      Progressive Matrices), language comprehension (Rustioni), academic achievement
      (IPDA), and problem behavior (Disruptive Behavior Disorder Rating Scale).
      RESULTS: Children diagnosed with a FASD achieved lower scores than control
      children on Verbal, Performance, and Full Scale IQ. Profile analysis of the WISC
      R indicates overall differences between the groups. However, some intact
      functioning within the FASD group was found, as the Similarities and Vocabulary
      subtests were similar to the controls. After an alpha adjustment to 0.004, the
      Block Design, Object Assembly, and Mazes subtests were significantly different
      from controls. On tests of nonverbal reasoning, language comprehension, and
      academic achievement, the children with a FASD scored significantly lower.
      Moreover, teachers rated children with a severe diagnosis within FASD as showing
      more inattentive symptoms than controls, while hyperactive/impulsive
      characteristics among children with a FASD were comparable with the control
      children. Significant correlations between head circumference, child
      dysmorphology, WISC-R, and Raven CPM scores are also reported. CONCLUSIONS: This
      study indicates that a sample of Italian children with a FASD, when compared with
      control children, display poorer functioning on measures of general intelligence,
      nonverbal reasoning, academic achievement, and teacher-rated problem behaviors.
      The findings also contribute to the formulation of a neuropsychological profile
      of children diagnosed with a FASD.

PMID- 18715278
TI  - Markers of oxidative stress and systemic vasoconstriction in pregnant women
      drinking > or =48 g of alcohol per day.
AB  - BACKGROUND: The precise pathway by which alcohol causes the characteristic
      features of fetal alcohol spectrum disorders is unknown. Proposed mechanisms for
      fetal injury from maternal alcohol use include cellular damage from oxidative
      stress and impaired fetal oxygenation related to maternal systemic
      vasoconstriction. Our objective was to compare the levels of urinary markers of
      oxidative stress and systemic vasoconstriction between women consuming large
      amounts of alcohol during pregnancy and women who did not drink alcohol during
      pregnancy. METHODS: Pregnant women consuming > or =48 g alcohol per day (n = 29)
      on average and pregnant women who abstained from alcohol use (n = 39) were
      identified using detailed interviews and home visits. Random maternal urine
      specimens were collected. Urinary levels of the oxidative stress marker, 8
      isoprostane F2alpha, and of the vasoactive prostaglandin metabolites, 2,3-dinor-6
      keto-prostaglandin F1alpha (a vasodilator) and 11-dehydro-thromboxane B2 (a
      vasoconstrictor), were measured using mass spectrometric methods. All analyte
      levels were corrected for urinary creatinine. RESULTS: In crude analyses, there
      was no significant difference in 8-isoprostane F2alpha between pregnant drinkers
      and nondrinkers (2.16 vs. 2.08 ng/mg creatinine, respectively, p = 0.87). There
      were no significant differences between the drinking and nondrinking groups in
      levels of 2,3-dinor-6-keto-prostaglandin F1alpha (1.03 vs. 1.17 ng/mg creatinine,
      respectively, p = 0.50), 11-dehydro-thromboxane B2 (0.72 vs. 0.59 ng/mg
      creatinine, respectively, p = 0.21), or the ratio of vasodilatory metabolite to
      vasoconstrictive metabolite (1.73 vs. 2.72, respectively, p = 0.14). Adjusting
      for maternal age, marital status, smoking, and gestational age at sampling did
      not substantially alter the results. CONCLUSION: Our results show no difference
      in levels of urinary eicosanoid markers of oxidative stress and systemic
      vasoconstriction between pregnant women who drink heavily and pregnant women who
      abstain. These findings speak against a role for maternal oxidative stress or
      systemic vasoconstriction in the pathogenesis of alcohol damage to the fetus.

PMID- 18715280
TI  - Likelihood of illegal alcohol sales at professional sport stadiums.
AB  - BACKGROUND: Several studies have assessed the propensity for illegal alcohol
      sales at licensed alcohol establishments and community festivals, but no previous
      studies examined the propensity for these sales at professional sport stadiums.
      In this study, we assessed the likelihood of alcohol sales to both underage youth
      and obviously intoxicated patrons at professional sports stadiums across the
      United States, and assessed the factors related to likelihood of both types of
      alcohol sales. METHODS: We conducted pseudo-underage (i.e., persons age 21 or
      older who appear under 21) and pseudo-intoxicated (i.e., persons feigning
      intoxication) alcohol purchase attempts at stadiums that house professional
      hockey, basketball, baseball, and football teams. We conducted the purchase
      attempts at 16 sport stadiums located in 5 states. We measured 2 outcome
      variables: pseudo-underage sale (yes, no) and pseudo-intoxicated sale (yes, no),
      and 3 types of independent variables: (1) seller characteristics, (2) purchase
      attempt characteristics, and (3) event characteristics. Following univariate and
      bivariate analyses, we a separate series of logistic generalized mixed regression
      models for each outcome variable. RESULTS: The overall sales rates to the pseudo
      underage and pseudo-intoxicated buyers were 18% and 74%, respectively. In the
      multivariate logistic analyses, we found that the odds of a sale to a pseudo
      underage buyer in the stands was 2.9 as large as the odds of a sale at the
      concession booths (30% vs. 13%; p = 0.01). The odds of a sale to an obviously
      intoxicated buyer in the stands was 2.9 as large as the odds of a sale at the
      concession booths (89% vs. 73%; p = 0.02). CONCLUSIONS: Similar to studies
      assessing illegal alcohol sales at licensed alcohol establishments and community
      festivals, findings from this study shows the need for interventions specifically
      focused on illegal alcohol sales at professional sporting events.

PMID- 18715279
TI  - Acute ethanol effects on local cerebral glucose utilization in select central
      nervous system regions of adolescent alcohol-preferring (P) and alcohol
      nonpreferring (NP) rats.
AB  - BACKGROUND: Alcohol abuse among adolescents is a major health and developmental
      problem. The 2-[(14)C]deoxyglucose (2-DG) technique allows for the in vivo
      quantification of local cerebral glucose utilization (LCGU) as a measure of
      functional neuronal activity. METHODS: Local cerebral glucose utilization rates
      were examined after acute ethanol administration within selected brain regions of
      adolescent alcohol-preferring (P) and -nonpreferring (NP) rats. Postnatal day 45
      male P and NP rats were injected with saline or 1.0 g/kg ethanol, i.p., 10
      minutes prior to an intravenous bolus of [(14)C]-2-deoxyglucose (125 microCi/kg).
      Image densities were determined using quantitative autoradiography and LCGU
      values calculated. RESULTS: Acute ethanol injection significantly decreased LCGU
      rates in select brain regions including the olfactory tubercles, the frontal
      cortex (Fr), and subregions of the posterior hippocampus (pCA1 and pCA3). Acute
      ethanol had no significant effects on LCGU rates in any region of the adolescent
      NP rats. Significant basal LCGU rate differences were apparent between the rat
      lines in a nearly global fashion with adolescent P rats having much higher basal
      LCGU rates compared with adolescent NP rats. CONCLUSIONS: These findings suggest
      that the adolescent P and NP rats are less sensitive to the effects of acute
      ethanol than their adult counterparts. The adolescent P rat is relatively more
      sensitive to the initial effects of acute ethanol in select brain regions as
      compared with the adolescent NP rat. Additionally, the innate hyper-excited state
      of the adolescent P central nervous system is a likely factor in the development
      of their high alcohol drinking behaviors.

PMID- 18715281
TI  - Pentylenetetrazole-induced status epilepticus following training does not impair
      expression of morphine-induced conditioned place preference.
AB  - Learning and memory play an important role in morphine addiction. Status
      epilepticus (SE) can impair the spatial and emotional learning and memory.
      However, little is known about the effects of SE on morphine-induced conditioned
      place preference (CPP). The present study was designed to investigate the effects
      of SE on morphine CPP, with food CPP being used as a control. The effects of SE
      on spatial memory in the Morris water maze (MWM) and Y-maze were investigated. SE
      was induced in adult mice using intraperitoneal injection of pentylenetetrazole;
      control mice received saline. The data indicated that SE had no effects on the
      formation of morphine CPP; however, the formation of food CPP was blocked by SE.
      Meanwhile, spatial memory assayed in the MWM and Y-maze was impaired by SE. In
      addition, the data demonstrated that SE did not cause a lasting disturbance of
      motor activity nor a change in the mice's appetite. These results suggested that
      although SE had no effects on morphine CPP, there was impaired food CPP and
      spatial memory in both the MWM and the Y-maze. The mechanisms underlying memory
      process of morphine CPP may be different from other types of memory.

PMID- 18715282
TI  - The dopamine D Receptor (DRD4) gene exon III polymorphism, problematic alcohol
      use and novelty seeking: direct and mediated genetic effects.
AB  - The present study sought to integrate convergent lines of research on the
      associations among the dopamine D(4) receptor (DRD4) gene, novelty seeking and
      drinking behaviors with the overall goal of elucidating genetic influences on
      problematic drinking in young adulthood. Specifically, this study tested a model
      in which novelty seeking mediated the relationship between DRD4 variable number
      of tandem repeats (VNTR) genotype and problematic alcohol use. Participants (n =
      90, 40 females) were heavy-drinking college students. Analyses using a structural
      equation modeling framework suggested that the significant direct path between
      DRD4 VNTR genotype and problematic alcohol use was reduced to a trend level in
      the context of a model that included novelty seeking as a mediator, thereby
      suggesting that the effects of DRD4 VNTR genotype on problematic alcohol use
      among heavy-drinking young adults were partially mediated by novelty seeking.
      Cross-group comparisons indicated that the relationships among the model
      variables were not significantly different in models for men versus women. These
      results extend recent findings of the association between this polymorphism of
      the DRD4 receptor gene, problematic alcohol use and novelty seeking. These
      findings may also help elucidate the specific pathways of risk associated with
      genetic influences on alcohol use and abuse phenotypes.

PMID- 18715283
TI  - Very low dose naltrexone addition in opioid detoxification: a randomized,
      controlled trial.
AB  - Although current treatments for opioid detoxification are not always effective,
      medical detoxification remains a required step before long-term interventions.
      The use of opioid antagonist medications to improve detoxification has produced
      inconsistent results. Very low dose naltrexone (VLNTX) was recently found to
      reduce opioid tolerance and dependence in animal and clinical studies. We decided
      to evaluate safety and efficacy of VLNTX adjunct to methadone in reducing
      withdrawal during detoxification. In a multi-center, double-blind, randomized
      study at community treatment programs, where most detoxifications are performed,
      174 opioid-dependent subjects received NTX 0.125 mg, 0.250 mg or placebo daily
      for 6 days, together with methadone in tapering doses. VLNTX-treated individuals
      reported attenuated withdrawal symptoms [F = 7.24 (2,170); P = 0.001] and reduced
      craving [F = 3.73 (2,107); P = 0.03]. Treatment effects were more pronounced at
      discharge and were not accompanied by a significantly higher retention rate.
      There were no group differences in use of adjuvant medications and no treatment
      related adverse events. Further studies should explore the use of VLNTX, combined
      with full and partial opioid agonist medications, in detoxification and long-term
      treatment of opioid dependence.

PMID- 18715284
TI  - High density lipoprotein-cholesterol levels increase with age in American women
      but not in Hong Kong Chinese women.
AB  - OBJECTIVES: High-density lipoprotein (HDL) cholesterol is a powerful
      cardiovascular risk factor. Important gender and ethnic differences in plasma HDL
      levels exist and warrant investigation. DESIGN: Cross-sectional survey in two
      different general populations. Patients 7700 participants of the National Health
      and Nutrition Examination Survey (NHANES) 1999-2002 and 1944 participants of the
      Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2) 2000-2004.
      MEASUREMENTS: Plasma HDL levels. RESULTS: Plasma HDL levels were higher in women
      than in men in both populations. In the United States women, it increased with
      age, whereas in Chinese women, it declined with age and converged with male HDL
      levels. In the United States, 37.1 +/- 1.2% men and 38.9 +/- 1.1% women had low
      HDL levels. In Hong Kong, 34.3 +/- 1.6% men and 34.5 +/- 1.5% women had low HDL
      levels. In Americans, the independent predictors of low HDL levels were lower
      age, being non-Mexican Hispanic, waist circumference, triglycerides and not
      drinking alcohol in men, and lower age, being Hispanic, waist circumference,
      triglycerides, current smoking and not drinking alcohol in women. In Hong Kong
      Chinese, the independent predictors of low HDL levels were body mass index,
      triglycerides, current smoking and not drinking alcohol in men, and lower age,
      waist circumference, triglycerides, diabetes and former smoking in women.
      CONCLUSIONS: The decline in plasma HDL with age in Chinese women is opposite to
      that seen in American women. The increased cardiovascular risk in elderly Chinese
      women requires further study.

PMID- 18715285
TI  - A novel vertebrate model of Staphylococcus aureus infection reveals phagocyte
      dependent resistance of zebrafish to non-host specialized pathogens.
AB  - With the emergence of multiply resistant Staphylococcus aureus, there is an
      urgent need to better understand the molecular determinants of S. aureus
      pathogenesis. A model of staphylococcal pathogenesis in zebrafish embryos has
      been established, in which host phagocytes are able to mount an effective immune
      response, preventing overwhelming infection from small inocula. Myeloid cell
      depletion, by pu.1 morpholino-modified antisense injection, removes this immune
      protection. Macrophages and neutrophils are both implicated in this immune
      response, phagocytosing circulating bacteria. In addition, in vivo
      phagocyte/bacteria interactions can be visualized within transparent embryos. A
      preliminary screen for bacterial pathogenesis determinants has shown that strains
      bearing mutations in perR, pheP and saeR are attenuated. perR and pheP mutants
      are deficient in growth in vivo, and their virulence is not fully restored by
      myeloid cell depletion. On the other hand, saeR mutants are able to grow in vivo,
      and are completely restored to virulence by myeloid cell depletion. Thus specific
      pathogen gene function can be matched with particular facets of host response.
      Zebrafish are a new addition to the tools available for the study of S. aureus
      pathogenesis, and may provide insights into the interactions of bacterial and
      host genomes in determining the outcome of infection.

PMID- 18715286
TI  - Stable implantation of orthogonal sensor circuits in Gram-negative bacteria for
      environmental release.
AB  - A broad host range, orthogonal genetic platform has been developed to format
      sensor circuits in the chromosome of Gram-negative microorganisms destined for
      environmental release as bioindicators of toxic or perilous compounds (e.g.
      explosives) in soil. The genetic scheme includes the generation of a genomic
      landing pad for the sensor module with a Tn5-mini-transposon bearing an optimal
      attTn7 sequence and a choice of reporter systems with optical and enzymatic
      outputs. The array of functional elements thereby inserted in the chromosome
      match that of a cognate plasmid vector which delivers the transcription factors
      and the promoters to a frame that places the regulatory parts in front of the
      reporters. Site-specific recombination sites allow the deletion of antibiotic
      resistances and enables reporter output prior to deliberate release. The system
      thus allows the production and maintenance of cells in a pre-release state and
      its intentional conversion in deliverable strains that fulfil all safety,
      stability and performance criteria. The combination of such a genetic platform
      with a variant of the transcriptional regulator XylR of Pseudomonas putida that
      responds to 2,4-dinitrotoluene has been the basis for the production of strains
      that emit light upon exposure to residues of explosives in a soil microcosm.

PMID- 18715288
TI  - Resistin increases islet blood flow and decreases subcutaneous adipose tissue
      blood flow in anaesthetized rats.
AB  - AIM: Resistin is an adipokine which has been suggested to participate in the
      induction of insulin resistance associated with type 2 diabetes. The aim of the
      present study was to investigate whether acute administration of resistin
      influences tissue blood perfusion in rats. METHODS: Resistin was administered as
      an intravenous infusion of 7.5 microg h(-1) (1.5 mL h(-1)) for 30 min to rats
      anaesthetized with thiobutabarbital. A microsphere technique was used to estimate
      the blood flow to six different depots of white adipose tissue (WAT), brown
      adipose tissue (BAT), as well as to the pancreas, islets, duodenum, colon,
      kidneys, adrenal glands and liver. RESULTS: Resistin administration led to an
      increased blood flow to the pancreas and islets and a decrease in subcutaneous
      WAT and BAT. Intra-abdominal white adipose tissue blood flow and that to other
      organs were not affected. CONCLUSION: Acute administration of resistin markedly
      affects the blood perfusion of both the pancreas and subcutaneous white adipose
      tissue depots. At present it is unknown whether resistin exerts a direct effect
      on the vasculature, or works through local or systemic activation of endothelial
      cells and/or macrophages. The extent to which this might contribute to the
      insulin resistance caused by resistin is yet unknown.

PMID- 18715289
TI  - Cicatricial alopecias.

PMID- 18715290
TI  - Etiology of cicatricial alopecias: a basic science point of view.
AB  - This article presents a short summary of our current knowledge of cicatricial
      alopecia disease pathogenesis and the hypothetical disease mechanisms that may be
      involved in scarring alopecia development. Several forms of scarring alopecia
      likely involve targeted cytotoxic action against hair follicle cells mediated by
      a folliculocentric inflammation. However, the specific nature of the inflammatory
      interference in hair follicle growth is open to question. A popular hypothesis of
      lymphocyte-mediated scarring alopecia development involves autoimmune targeting
      of hair follicle-specific self-antigens, although there is no direct evidence in
      support of such a view. Alternative hypotheses focus on defects in sebaceous
      gland function, destruction of hair follicle stem cells, and interference in the
      communication between hair follicle mesenchyme and epithelium. Many questions
      arise from these hypotheses, and addressing them with a systematic research
      approach may enable significant advances in understanding cicatricial alopecia
      etiology.

PMID- 18715291
TI  - Cicatricial alopecia: classification and histopathology.
AB  - Primary cicatricial alopecias are a diagnostically challenging group of disorders
      characterized by folliculocentric inflammation resulting in destruction of hair
      follicles and irreversible hair loss. They are classified according to a
      consensus-issued classification scheme based on the predominant cell type
      present: lymphocytic, neutrophilic, or mixed. Histopathology is a pivotal
      component of the diagnostic evaluation. Early diagnosis is critical since timely
      institution of treatment can halt progression of permanent hair loss. Salient
      histopathologic findings are presented in this review, along with adjunctive
      clues derived from interpretation of special stains and direct immunofluorescence
      studies. Despite careful evaluation, accurate diagnosis may remain elusive in
      some instances. The primary cicatricial alopecias often share overlapping
      features. The highest diagnostic yield is procured when histology is correlated
      with the clinical presentation.

PMID- 18715292
TI  - Folliculitis decalvans.
AB  - Folliculitis decalvans is a rare inflammatory scalp disorder. The present paper
      gives a practical approach to diagnosis and patient management and reviews
      possible pathogenetic factors and treatment options. Folliculitis decalvans is
      classified as primary neutrophilic cicatricial alopecia and predominantly occurs
      in middle-aged adults. Staphylococcus aureus and a deficient host immune response
      seem to play an important role in the development of this disfiguring scalp
      disease. Lesions occur mainly in the vertex and occipital area. Clinically, the
      lesions present with follicular pustules, lack of ostia, diffuse and
      perifollicular erythema, follicular tufting, and, oftentimes, hemorrhagic crusts
      and erosions. Histology displays a mainly neutrophilic inflammatory infiltrate in
      early lesions and additionally lymphocytes and plasma cells in advanced lesions.
      Treatment is focused on the eradication of S. aureus anti-inflammatory agents.

PMID- 18715293
TI  - Cicatricial alopecia: discoid lupus erythematosus.
AB  - Chronic cutaneous lupus erythematosus consists of three major dermatologic
      diseases: discoid lupus erythematosus (DLE), lupus panniculitis/lupus profundus,
      and lupus tumidus (Table 1). DLE is estimated to be responsible for 50-85% of
      patients with chronic cutaneous lupus erythematosus. Scalp involvement is most
      often the presenting symptom. The clinical features and diagnosis of DLE, its
      pathophysiology and treatment, are reviewed.

PMID- 18715294
TI  - Lichen planopilaris.
AB  - Lichen planopilaris is a chronic scarring alopecia characterized by follicular
      hyperkeratosis, perifollicular erythema, and loss of follicular orifices. The
      scalp lesions may be single or multiple and commonly involve the vertex and
      parietal area. The hair follicles at the margin of the alopecic patches reveal
      perifollicular erythema. Anagen hairs can be pulled out easily in active lesions.
      Associated cutaneous, nail, and mucous membrane lichen planus may be present.
      Commonly encountered symptoms and signs are increased hair shedding, itching,
      scaling, burning, and tenderness. Differentiation from other cicatricial alopecia
      can be performed through meticulous evaluation of the clinical, histopathologic,
      and immunohistopathologic findings. Treatment strategies depend on the disease
      activity and physician expertise. Although there are no definitive curative
      modalities, some new discoveries and conceptual advances continue to broaden our
      treatment options of this complex condition.

PMID- 18715295
TI  - Pseudopelade of Brocq.
AB  - Pseudopelade of Brocq (PPB) is a rare, idiopathic, slowly progressive hair
      disorder, resulting in cicatricial alopecia. It typically presents in Caucasian
      adult patients as small, smooth, flesh-toned and slightly depressed alopecic
      patches with irregular outlines. It primarily involves the parietal and vertex
      portions of the scalp with a chronic prolonged course. Controversial opinions
      still exist as to whether PPB is a single entity or an end stage of several
      cicatricial alopecic disorders. A practical approach to diagnosis of PPB and
      therapeutic update are discussed in this review.

PMID- 18715296
TI  - Central scalp alopecia photographic scale in African American women.
AB  - Central centrifugal cicatricial alopecia (CCCA) is a common but poorly understood
      cause of hair loss in African American women. A photographic scale was developed
      that captures the pattern and severity of the central hair loss seen with CCCA in
      order to help identify this problem in the general community and to potentially
      correlate clinical data with hair loss. The utility and reproducibility of this
      photographic scale was determined in a group of 150 African American women
      gathered for a health and beauty day who were evaluated by both four
      investigators experienced in the diagnosis of hair disorders and by the subjects
      themselves.

PMID- 18715297
TI  - Central centrifugal cicatricial alopecia.
AB  - A progressive scarring alopecia of the central scalp is commonly seen in young to
      middle-aged females of African descent. It usually starts at the vertex or mid
      top of the scalp and gradually spreads centrifugally, hence, the unifying term of
      central centrifugal cicatricial alopecia. The clinical pattern is suggestive of
      female pattern alopecia, but a lack of follicular pores indicative of scarring is
      present. It can progress for years before slowly burning out. The etiology is
      unknown but genetic factors may be important. It is often associated with a
      history of traumatic hairstyling involving heat, traction, and chemicals.
      However, most patients of African descent without this disorder have similar
      styling habits. Nonetheless, avoidance of physical and chemical trauma to the
      scalp hair, the use of suitable shampoos and conditioners, and the encouragement
      of natural hairstyles may be helpful. Any infection should be treated. Topical or
      intralesional corticosteroids and systemic antibiotics may be useful and topical
      minoxidil should be tried with the hope of preventing further scarring and
      encouraging regrowth of recovering follicles. Current research into the etiology
      of this disorder will help to foster much-needed clinical trials of therapeutic
      agents.

PMID- 18715298
TI  - Secondary cicatricial and other permanent alopecias.
AB  - Various nonfollicular scalp conditions can cause secondary scarring or permanent
      alopecia. Possible causes are congenital defects, trauma, inflammatory
      conditions, infections, and neoplasms (rarely drugs). Associated signs and
      symptoms and other diagnostic procedures such as histopathology may aid in the
      diagnosis. Detection of the underlying disorder may be difficult in end-stage
      lesions. Treatment is specific for active conditions. Surgery and hair
      transplantation are options for localized scars.

PMID- 18715299
TI  - The surgical treatment of cicatricial alopecia.
AB  - Surgical correction of cicatricial alopecia can yield exceptional results when
      performed in the appropriate clinical scenario. To facilitate determination of
      the most suitable corrective therapy, we propose two new categories of
      cicatricial alopecia: "unstable" and "stable." Unstable cicatricial alopecia is
      intermittent and results in possible subsequent scarring hair loss in either new
      or old areas. Stable cicatricial alopecia, on the other hand, refers to fixed
      permanent scarring. While surgical excision is preferred to hair transplantation
      for both categories of cicatricial alopecia, this preference is even stronger in
      cases of unstable cicatricial alopecia due to its intermittent and progressive
      nature. Regardless of which corrective technique is used, analysis of specific
      physical patient characteristics coupled with a careful view towards the possible
      evolution of male pattern baldness or female pattern hair loss are essential to
      achieve superior long-term results. Herein we also outline guidelines for
      identifying these physical traits as well as for performing hair transplantation
      and surgical excision in order to achieve optimal cosmetic outcomes and minimize
      postoperative complications.

PMID- 18715300
TI  - Pineal system of desert rodents and its relationship to the epithalamus.
AB  - The morphological relationships of the pineal complex to the epithalamic
      structures have been examined at light microscopic level in five desert rodent
      species, Meriones crassus, Meriones lybicus, Gerbillus gerbillus, Psammomys
      obesus and Ctenodactylus vali. The pineal complex is classified as type ABC in M.
      crassus and G. gerbillus, AC in M. lybicus, AbetaC in P. obesus and alphabetaC in
      C. vali. In these rodent species, the pineal is an elongated organ which is
      dumbbell-shaped in G. gerbillus and M. lybicus, and extends above the cerebral
      hemispheres in M. crassus, leaf-shaped in P. obesus and lancet-shaped in C. vali.
      In P. obesus, pigment-containing cells are noted in the superficial part of the
      gland. In all species examined, the suprahabenular recess which is an extension
      of the choroid plexus of the third ventricule establishes a close anatomical
      relationship with the deep pineal. In C. vali, the suprahabenular recess is also
      contiguous with the pineal stalk and the superficial pineal component. In M.
      lybicus, M. crassus, G. gerbillus and P. obesus, a prominent dorsal vessel, the
      vena cerebri magna, intervenes between the suprahabenular recess, the superficial
      portion and the stalk. The most striking feature noted in this study is the
      presence of numerous melanocytes in the connective tissue capsule of the pineal
      gland, in the connecting stalk and in the connective tissue core of the highly
      convoluted suprahabenular recess in M. lybicus and M. crassus. The location of
      melanocytes in the restricted pineal area may suggest that these cells have a
      morphosignificance in photoreception or photoprotection.

PMID- 18715301
TI  - Reducing the inequalities in indigenous health: a new way forward.

PMID- 18715302
TI  - Job variation in Australian advanced training in neurology: what are the
      implications?

PMID- 18715303
TI  - A fire inside: current concepts in chronic pancreatitis.
AB  - Chronic pancreatitis is a necroinflammatory process characterized pathologically
      by acinar atrophy and fibrosis and clinically by abdominal pain, diabetes and
      maldigestion. In this review we summarize some of the recent advances in the
      understanding of the pathogenesis of pancreatitis and how they have shaped our
      current understanding of chronic pancreatitis. We pay particular attention to
      advances in the genetic basis of idiopathic, hereditary and tropical pancreatitis
      as well as research into the relationship between alcohol and the pancreas. We
      have also reviewed current practices with respect to diagnosis and management of
      chronic pancreatitis.

PMID- 18715304
TI  - Coronary heart disease is associated with regional grey matter volume loss:
      implications for cognitive function and behaviour.
AB  - Coronary heart disease (CHD) has been associated with impaired cognition, but the
      mechanisms underlying these changes remain unclear. We designed this study to
      determine whether adults with CHD show regional brain losses of grey matter
      volume relative to controls. We used statistical parametric mapping (SPM5) to
      determine regional changes in grey matter volume of T(1)-weighted magnetic
      resonance images of 11 adults with prior history of myocardial infarction
      relative to seven healthy controls. All analyses were adjusted for total grey and
      white matter volume, age, sex and handedness. CHD participants showed a loss of
      grey matter volume in the left medial frontal lobe (including the cingulate),
      precentral and postcentral cortex, right temporal lobe and left middle temporal
      gyrus, and left precuneus and posterior cingulate. CHD is associated with loss of
      grey matter in various brain regions, including some that play a significant role
      in cognitive function and behaviour. The underlying causes of these regional
      brain changes remain to be determined.

PMID- 18715305
TI  - Atypical antipsychotic-induced diabetes mellitus: an update on epidemiology and
      postulated mechanisms.
AB  - Diabetic ketoacidosis and hyperglycaemic hyperosmolar syndrome are rare, but
      potentially fatal complications of antipsychotic-associated hyperglycaemia. The
      mechanisms for this remain unclear, but are probably multifactorial. The
      suggested reasons include drug-induced weight gain and adiposity, development of
      the metabolic syndrome, antagonism of serotonin (5-hydroxytryptamine) receptors,
      drug-induced leptin resistance, dyslipidaemia mediated pancreatic beta-cell
      damage and hepatocyte transcription factor dysregulation. Patients with
      schizophrenia are known to be at a higher genetic risk of developing diabetes
      mellitus and cardiovascular disease. This review emphasizes a rare case of
      hyperosmolar hyperglycaemic syndrome in a young man with schizophrenia and
      discusses proposed mechanisms for the development of antipsychotic-associated
      diabetes mellitus.

PMID- 18715306
TI  - Case of vancomycin-induced linear immunoglobulin A bullous dermatosis.

PMID- 18715307
TI  - Electrocardiographic changes in hypothermia.

PMID- 18715308
TI  - Mollaret's meningitis and pituitary failure associated with a Rathke's cleft
      cyst.

PMID- 18715309
TI  - Thyroid dysfunction due to over-the-counter usage of tiratricol.

PMID- 18715310
TI  - Autonomy and advance care plans: a relationship oversimplified.

PMID- 18715311
TI  - Pulmonary hypertension complicating sarcoidosis.

PMID- 18715312
TI  - Diagnostic test thresholds.

PMID- 18715315
TI  - Method of cut point selection biases diagnostic research.

PMID- 18715316
TI  - Enhancing academic physician training.

PMID- 18715318
TI  - Preventing hepatitis B virus reactivation following immunosuppressive therapy.

PMID- 18715319
TI  - The flowering of systems approaches in plant and crop biology.

PMID- 18715320
TI  - The chloroplast as a regulator of Ca2+ signalling.

PMID- 18715321
TI  - Great leap forward? Transposable elements, small interfering RNA and adaptive
      Lamarckian evolution.

PMID- 18715322
TI  - Genetic underpinnings of postzygotic reproductive barriers among plants.

PMID- 18715323
TI  - Plant hydraulics: new discoveries in the pipeline.

PMID- 18715324
TI  - Comprehensive gene expression atlas for the Arabidopsis MAP kinase signalling
      pathways.
AB  - * Mitogen activated protein kinase (MAPK) pathways are signal transduction
      modules with layers of protein kinases having c. 120 genes in Arabidopsis, but
      only a few have been linked experimentally to functions. * We analysed microarray
      expression data for 114 MAPK signalling genes represented on the ATH1 Affymetrix
      arrays; determined their expression patterns during development, and in a wide
      range of time-course microarray experiments for their signal-dependent
      transcriptional regulation and their coregulation with other signalling
      components and transcription factors. * Global expression correlation of the MAPK
      genes with each of the represented 21 692 Arabidopsis genes was determined by
      calculating Pearson correlation coefficients. To group MAPK signalling genes
      based on similarities in global regulation, we performed hierarchical clustering
      on the pairwise correlation values. This should allow inferring functional
      information from well-studied MAPK components to functionally uncharacterized
      ones. Statistical overrepresentation of specific gene ontology (GO) categories in
      the gene lists showing high expression correlation values with each of the MAPK
      components predicted biological themes for the gene functions. * The combination
      of these methods provides functional information for many uncharacterized MAPK
      genes, and a framework for complementary future experimental dissection of the
      function of this complex family.

PMID- 18715326
TI  - The role of general practitioners in migraine management.
AB  - General practitioners (GPs) play a pivotal role in managing migraine and ensuring
      that patients have a positive first experience when seeking treatment. A large
      proportion of migraineurs do not consult a GP, preferring to rely on over-the
      counter remedies to reduce pain and disability. For those who do consult,
      receiving a satisfactory outcome at their first consultation is important for
      ensuring subsequent effective management of their migraine. If patient
      expectations are not met at their first visit (prescribed treatment is
      ineffective or GP does not empathize with their suffering), patients may not
      return for further consultation. There remains a need to improve migraine
      diagnosis and treatment, and GPs require continuing medical education and
      neurologist support to ensure that they are providing the best migraine
      treatments and outcomes. More widespread use of diagnostic tools, standardized
      management guidelines and individualized treatment regimens will help GPs
      successfully manage both migraine symptoms and patient expectations.

PMID- 18715327
TI  - Emergency treatment of migraine.
AB  - During the past few years, several surveys have highlighted the high prevalence
      of migraine amongst the general French population and the large healthcare burden
      associated with suboptimal treatment. Since it opened, the Centre d'Urgences
      Cephalees (EHC) has treated more than 55 000 patients, the majority of whom were
      suffering from migraine. Expert diagnosis of the type and causes of the headache,
      followed by immediate medication, allows patient stabilization. Detailed
      assessments can then determine the most appropriate treatment for each patient to
      improve outcomes and reduce the necessity for further emergency admissions.
      Triptans are generally recommended, and for those patients who currently have
      ineffective migraine control with one triptan, individual evaluation allows
      prescription of an alternative triptan which will better suit their needs. Follow
      up is crucial to ensure that treatment remains optimal and that patient
      expectations are being met. Although a minority of patients with severe headache
      will continue to require repeated emergency treatment, more than 90% of patients
      seen at the EHC can be successfully managed with this combination of accurate
      diagnosis, effective treatment and individualized follow-up care.

PMID- 18715328
TI  - Almotriptan in triptan-naive patients: new evidence of benefits.
AB  - Although triptans represent the standard of care for migraine that is severe,
      disabling and/or suboptimally responsive to migraine non-specific analgesia, they
      are often underused in clinical practice. Simple analgesics and non-steroidal
      anti-inflammatory drugs (NSAIDs) may provide effective treatment in some
      patients, but it is an inadequate response to these drugs that drives the
      therapeutic progression to triptans at the end of the traditional 'step-care'
      approach. However, there are several disadvantages to this approach. It may cause
      patients to lose confidence in their physician during this hierarchical 'trial
      and-error' search for optimal treatment when prescribed medications are
      ineffective, leading them to cease consulting before triptans are tried. It may
      also result in a protracted time interval of suboptimal treatment, with
      unnecessary suffering in patients who are triptan candidates. The alternative
      approach of 'stratified care', in which medication is prescribed according to the
      severity of symptoms, enables triptans to be used earlier in the treatment plan,
      especially when triptan candidates are given a choice between simple
      analgesic/NSAID and triptan medication from the start. This raises the question
      about the efficacy of triptans in triptan-naive (TN) patients. A recent
      exploratory post-hoc analysis compared the effect of almotriptan 12.5 mg in TN
      patients (n = 342) with that in triptan-experienced patients (n = 237).
      Almotriptan was effective in both cohorts with a consistent trend in favour of
      the efficacy of almotriptan in TN patients, notably for sustained pain freedom
      (SPF) and SPF plus no adverse events. Moreover, both headache recurrence at 24 h
      and the use of rescue medication was lower in the TN patients, whereas
      tolerability was equally good in both cohorts. These findings indicate that TN
      patients can expect excellent symptom control when they progress from non
      specific analgesia to treatment with almotriptan and support the earlier use of
      triptans in line with the stratified care paradigm.

PMID- 18715329
TI  - Pathways to the best fit of triptans for migraine patients.
AB  - Variability in drug response is a major barrier to the successful treatment of
      migraine, and most treatments are only optimal in a subset of patients. Although
      triptans provide the best therapeutic option for the treatment of acute migraine,
      it has not previously been possible to predict how well patients will respond to
      a specific triptan or whether they will experience unpleasant adverse events.
      Hence, it has been difficult for physicians to match individual patients with the
      most suitable agent to treat their migraine pain. Intrapatient variability has
      been associated with polymorphisms in genes encoding drug-metabolizing enzymes,
      drug transporters and drug targets. Pharmacogenetics provides the possibility of
      tailoring the therapeutic approach to individual patients, in order to maximize
      treatment efficacy while minimizing the potential for unwanted side-effects. This
      review demonstrates how almotriptan may overcome genetically determined responses
      by utilizing diverse metabolic pathways to provide therapeutic benefit to many
      migraineurs.

PMID- 18715330
TI  - Early treatment in migraine: how strong is the current evidence?
AB  - Over the last 10 years, triptans (serotonin 5-HT(1B/1D) receptor agonists) have
      proved to be efficacious in treating migraine pain. However, recent evidence
      suggests that patients are still not receiving optimal pain management,
      particularly in clinical trials, where triptan treatment is generally not
      initiated until pain has reached moderate intensity. Pathophysiological evidence
      indicates that if treatment is initiated at an early stage, while pain is still
      mild and before the onset of central sensitization, outcomes for patients may be
      improved. In addition, a small number of clinical trials have been reported in
      which triptans were taken early (within 1 h of pain onset) or while pain was
      still mild; although constraints of trial design and data analysis limit definite
      conclusions, overall the results suggest that this early/mild approach results in
      more rapid and sustained pain relief. New studies are therefore needed to clarify
      the clinical benefits of early treatment, whilst taking into account potential
      risks, such as medication overuse. Ultimately, migraine treatment strategies
      require optimization in order to meet patient expectations and to reduce the
      current burden of migraine-associated disability.

PMID- 18715331
TI  - The 'Act when Mild' (AwM) study: a step forward in our understanding of early
      treatment in acute migraine.
AB  - An important issue in the management of migraine is the advice given to patients
      as to when to take their treatment in the course of the attack. While it seems
      common sense almost to take treatment early in the attack, the evidence base for
      that advice is not as robust as could be expected. The 'Act when Mild' (AwM)
      Study was a randomized, four-arm, multicentre, multinational, double-blind,
      placebo-controlled trial of almotriptan (12.5 mg) to compare outcomes after
      administration of treatment when pain intensity was mild and within 1 h of
      headache onset (mild/early) with outcomes when pain had become moderate or
      severe. Of 491 migraineurs enrolled, 403 were evaluable with an intention-to
      treat population (ITT) of 404. At the primary end-point, 2 h pain free, on the
      ITT analysis 49% of patients in the almotriptan 12.5 mg treat early/mild group
      and 40% in the treat moderate/severe group had responded (P = 0.21). Of these
      patients, 43 did not take medication according to their randomly allocated
      baseline pain intensity (mild or moderate/severe) and were subsequently
      reassigned, prior to study unblinding, to the appropriate group (AwM population)
      for re-analysis of the primary outcome measure: 2-h pain-free rates. In the
      almotriptan arms, 53% of the mild/early group and 37.5% of the moderate/severe
      group were pain free at 2 h (P = 0.02; AwM population). The corresponding
      proportions in the placebo groups were 24.7% and 17.5% (significantly lower than
      the respective almotriptan arms; P </= 0.01). Considering the ITT population,
      secondary end-points were also significantly in favour of treatment with
      almotriptan in the mild/early vs. the moderate/severe stage, including: sustained
      pain-free, 45.6% vs. 30.5% (P = 0.02); headache recurrence at 24 h, 6% vs. 24% (P
      = 0.0124). Adverse events were reported in < 5% of patients, with no significant
      differences between almotriptan and placebo and no serious events in any group.
      Treatment with almotriptan while migraine pain is still mild and within 1 h of
      onset provides statistically significant and clinically relevant enhancements in
      efficacy compared with waiting until pain has reached higher severity levels.

PMID- 18715332
TI  - Applying the benefits of the AwM study in the clinic.
AB  - The Act when Mild (AwM) Study has illustrated the benefits to migraineurs of
      taking triptan medication when their migraine pain is still mild and within 1 h
      of the onset of symptoms. Yet many patients wait until the attack has fully
      developed before taking their medication, with potentially inferior outcomes. In
      order to reproduce the benefits of early intervention using the AwM paradigm in
      daily practice, a number of key barriers need to be addressed at both the
      physician and patient level. Notable physician-related barriers to be overcome,
      particularly at the primary care level, include accuracy of an early diagnosis of
      migraine in newly presenting patients, communication skills that generate a
      therapeutic engagement with migraine patients and enhance patient confidence, the
      application of knowledge about up-to-date strategies to optimize treatment
      outcomes, and the setting of achievable goals to avoid unrealistic expectations.
      Patient-related obstacles that need to be identified and overcome encompass
      patient attitude, expectations, and behaviour. Migraine patients may be reluctant
      to consult their physician, and, of those who do, many stop consulting because
      they perceive that physicians can do little to improve their situation. For this
      reason, migraine patients need to be counselled about the most appropriate
      medication for their level of symptoms. Moreover, patients need to be confident
      before they will adhere routinely to the advice they receive, and high in the
      priority of advice is the use of medication, particularly triptans, at the first
      sign of a migraine attack, rather than waiting until their attack has progressed
      to moderate or severe intensity. Patients who adhere to this advice are likely to
      experience a notable reduction in the pain, disability and time lost that they
      would otherwise suffer. The beneficial effects of early triptan intervention
      illustrated in the AwM Study can therefore be best reproduced in the clinic if
      the correct advice given to patients is not only accepted and applied by them,
      but also followed up by their physician.

PMID- 18715338
TI  - Distribution and origin of bovine major histocompatibility complex class II DQA1
      genes in Japan.
AB  - We sequenced the major histocompatibility complex (MHC) class II DQA1 gene in 352
      Japanese cattle (95 Japanese Black, 91 Holstein, 102 Japanese Shorthorn and 64
      Jersey cattle) using a new sequence-based typing method. In total, 19 bovine MHC
      (BoLA)-DQA1 alleles, of which two were novel alleles, were detected. The
      Holstein, Jersey, Japanese Shorthorn and Japanese Black breeds had 13, 12, 10 and
      15 alleles, respectively. The dendrogram that was constructed by the neighbor
      joining method on the basis of the DQA1 gene allele frequencies of the four
      Japanese cattle breeds showed that the Holstein and Japanese Black breeds were
      closest to each other, with Jersey being farther from these two breeds than
      Japanese Shorthorn. In addition, Wu-Kabat analysis showed that the DQA1 alleles
      of the Holstein and Japanese Black were the most and least polymorphic,
      respectively. Phylogenetic analyses indicated that the DQA1 gene of Bovidae such
      as cattle, sheep, bison and goat were more similar to pig SLA-DQA genes than to
      human HLA-DQA1 and dog DLA-DQA genes. The cattle, goat, bison, sheep, human and
      pig DQA1 molecules had similar rates of amino acid sequence polymorphism, but the
      distribution of their polymorphic residues differed from that in the dog DQA1
      protein. However, the Bovidae DQA1 molecule had more polymorphic residues than
      the human, pig and dog DQA molecules at two regions, namely positions 52-53 and
      65-66. This indicates that the Bovidae DQA1 locus is more polymorphic than the
      DQA loci of other species.

PMID- 18715340
TI  - Nomenclature for factors of the HLA system, update April 2008.

PMID- 18715339
TI  - Associations between cytokine/cytokine receptor single nucleotide polymorphisms
      and humoral immunity to measles, mumps and rubella in a Somali population.
AB  - We genotyped a Somali population (n = 85; age < or =30 years) for 617 cytokine
      and cytokine receptor single nucleotide polymorphisms (SNPs) using Illumina
      GoldenGate genotyping to determine associations with measles, mumps and rubella
      immunity. Overall, 61 significant associations (P < or = 0.01) were found between
      SNPs belonging to cytokine receptor genes regulating T helper (Th)1 (IL12RB2,
      IL2RA and B) and Th2 (IL4R and IL10RB) immunity, and cytokine (IL1B, TNFA, IL6
      and IFNB1) and cytokine receptor (IL1RA, IFNAR2, IL18R1, TNFRSF1A and B) genes
      regulating innate immunity and variations in antibody levels to measles, mumps
      and/or rubella. SNPs within two major inflammatory cytokine genes, TNFA and
      interleukin (IL) 6, showed associations with measles-specific antibodies.
      Specifically, the minor allele variant of rs1799964 (TNFA -1211 C>T) was
      associated with primarily seronegative values (median enzyme immunoassay index
      values < or =0.87; P = 0.002; q = 0.23) in response to measles disease and/or
      vaccination. A heterozygous variant CT for rs2069849 (IL6 +4272C>T; Phe201Phe)
      was also associated with seronegative values and a lower median level of antibody
      response to measles disease and/or vaccination (P = 0.004; q = 0.36) or measles
      vaccination alone (P = 0.008). Several SNPs within the coding and regulatory
      regions of cytokine and cytokine receptor genes showed associations with mumps
      and rubella antibody levels but were less informative as strong linkage
      disequilibrium patterns and lower frequencies for minor alleles were observed
      among these SNPs. Our study identifies specific SNPs in innate immune response
      genes that may play a role in modulating antibody responses to measles
      vaccination and/or infection in Somali subjects.

PMID- 18715341
TI  - Nomenclature for factors of the HLA system, update May 2008.

PMID- 18715344
TI  - An analysis of the concept of organizational commitment.
AB  - TOPIC: Building organizational commitment. PURPOSE: This paper aims to analyze
      the concept of organizational commitment, including its attributes, antecedents,
      outcomes, and measurements. SOURCES OF INFORMATION: CINAHL, MEDLINE, Psychology
      and Behavioral Sciences Collection, Sociological Collection, and PubMed.
      CONCLUSION: By understanding the concept of organizational commitment,
      administrators and nurses can become more aware of their levels of commitment,
      bridge gaps in communication, and eventually provide higher-quality care to
      clients.

PMID- 18715345
TI  - Application of evidence-based practice through a float project.
AB  - Evidence-based practice must become a common, acceptable process for the bedside
      nurse. This paper demonstrates a process for engaging nurses in the use of
      evidence for direct practice. An example using the revision of a float policy is
      provided as a model for staff nurses to incorporate evidence in a mechanism to
      elicit change.

PMID- 18715346
TI  - The diversity imperative: strategies to address a diverse nursing workforce.
AB  - TOPIC: There has been a call to action for the need to create a more diverse
      nursing workforce. PURPOSE: The purpose of this article is to outline and review
      strategies that schools of nursing education can use to increase the recruitment,
      retention, and success of a diverse nursing student body. SOURCES OF INFORMATION:
      A review of the nursing literature was performed using CINAHL and hand-searching
      references. Abstracts were reviewed and articles included if the topic of the
      article referred to strategies to increase the diversity of nursing students.
      CONCLUSIONS: A variety of strategies are being used to address this issue. A
      multifaceted approach is recommended.

PMID- 18715347
TI  - Attitude: a concept analysis.
AB  - This paper presents a concept analysis conducted as a beginning step to
      developing research on nurses' attitudes toward advancing formal education. A
      literature review, conducted by the author, confirmed that the term attitude is
      used prolifically in nursing research; however, the findings were inconclusive as
      to a definition and the attributes of an "attitude." Often this concept was
      either not defined or vaguely defined. Few operational definitions, required for
      accurate measurement of a concept, were found. An adequate definition and
      understanding of a concept is required for critical reflection and utilization of
      the term and development of measurement procedures.

PMID- 18715348
TI  - A concept analysis of social capital within a health context.
AB  - PURPOSE: This paper aims to clarify the concept of social capital within a health
      context using Rodgers's (2000) Evolutionary Method. SOURCE: Published literature.
      CONCLUSIONS: The analysis demonstrates that social capital is the intangible
      assets, including trust, networks, and social norms of reciprocity, possessed by
      a society within a specific culture. When a unit (individual or a family)
      increases its sense of community or quality of community participation, this
      could increase its social capital. The result of this analysis provides a guide
      for further conceptual and empirical research and clinical practice.

PMID- 18715349
TI  - Said another way. Nursing care: a lost art.

PMID- 18715350
TI  - Practice week at a glance. Director of operations and advanced practice nurse.

PMID- 18715351
TI  - Home-use preventive and therapeutic oral products.

PMID- 18715352
TI  - Current concepts in toothbrushing and interdental cleaning.

PMID- 18715353
TI  - Toothpaste in the control of plaque/gingivitis and periodontitis.

PMID- 18715354
TI  - Dentine hypersensitivity: preventive and therapeutic approaches to treatment.

PMID- 18715355
TI  - Home-use oral hygiene products: mouthrinses.

PMID- 18715356
TI  - Oral hygiene products: potential for harm to oral and systemic health?

PMID- 18715357
TI  - Halitosis (breath odor).

PMID- 18715358
TI  - Over-the-counter remedies for oral soreness.

PMID- 18715359
TI  - Xerostomia.

PMID- 18715360
TI  - Host response modulation in periodontics.

PMID- 18715361
TI  - Probiotics and oral healthcare.

PMID- 18715362
TI  - An overview of tooth-bleaching techniques: chemistry, safety and efficacy.

PMID- 18715363
TI  - Addressing the topic of smoking cessation in a dental setting.

PMID- 18715364
TI  - Public policy and the market for dental services.
AB  - Social inequality in access to oral health care is a feature of countries with
      predominantly privately funded markets for dental services. Private markets for
      health care have inherent inefficiencies whereby sick and poor people have
      restricted access compared to their healthy and more affluent compatriots. In the
      future, access to dental care may worsen as trends in demography, disease and
      development come to bear on national oral healthcare systems. However, increasing
      public subsidies for the poor may not increase their access unless availability
      issues are resolved. Further, increasing public funding runs counter to policies
      that feature less government involvement in the economy, tax policy on private
      insurance premiums, tax reductions and, in some instances, free-trade agreements.
      We discuss these issues and provide international examples to illustrate the
      consequences of the differing public policies in oral health care. Subsidization
      of the poor by inclusion of dental care in social health insurance models appears
      to offer the most potential for equitable access. We further suggest that nations
      need to develop national systems capable of the surveillance of disease and human
      resources, and of the monitoring of appropriateness and efficiency of their oral
      healthcare delivery systems.

PMID- 18715372
TI  - There but for the grace.

PMID- 18715374
TI  - Quitting smoking: helping patients kick the habit.

PMID- 18715375
TI  - Quitting smoking: answers to common questions.

PMID- 18715376
TI  - Health literacy and health disparities: the role they play in maternal and child
      health.

PMID- 18715377
TI  - Families of two: meeting the needs of couples experiencing male infertility.

PMID- 18715378
TI  - Late preterm birth: a rising trend: part one of a two-part series.

PMID- 18715379
TI  - Late preterm infants: clinical complications and risk: part two of a two-part
      series.

PMID- 18715380
TI  - Respect in the workplace: tips and tools for creating an environment of respect.

PMID- 18715381
TI  - Unexplained infertility: can you guess the cause?

PMID- 18715382
TI  - Emergency contraception: when the pharmacist conscience clause restricts access.

PMID- 18715383
TI  - Safe prescribing habits: preventing medication errors in primary care.

PMID- 18715385
TI  - First of its kind HPV resource: AWHONN releases new guide for clinicians.

PMID- 18715386
TI  - Olivia's daughters.

PMID- 18715387
TI  - The scholarly work of Janice Morse: synthesis and reflection.
AB  - The author was afforded opportunity during her doctoral studies to compile and
      reflect upon the scholarly work of nurse researcher, Dr Janice Morse. Morse's
      refinement and development of patient-centred, empirically based concepts and
      theories, and her mastery of a diverse research repertoire, are an indisputable
      contribution to nursing knowledge. The author delineates four ways by which
      Morse's work contributes to nursing's disciplinary body of knowledge: (i) the
      consistent focus on the nurse-patient domain; (ii) the multiplicity of knowledge
      forms; (iii) the promotion of paradigm integration and methodological pluralism;
      and (iv) the predominance of prescriptive theories. Additionally, conjecture is
      put forth regarding the philosophical assumptions underpinning Morse's work.
      Morse serves as an excellent role model for nurse researchers who strive to
      ensure that nursing theories are amenable to clinical application, to research
      investigation and to utilization as a pedagogical tool.

PMID- 18715388
TI  - Knowledge and management of infants' pain by mothers in Ile Ife, Nigeria.
AB  - Mothers' knowledge and management of pain in infants were assessed in this study.
      A total of 130 mothers from two health centres in Ile Ife, Southwest, Nigeria
      were selected by systematic sampling method. Only 3.8% indicated that neonates
      experience pain. Malaria (46.2%) was the major cause of pain identified.
      Analgesic/antimalarials (56.9%) and breastfeeding (16.9%) are used in pain
      relief. To improve the quality of life of infants, mothers must be educated on
      the assessment, early detection and management of pain.

PMID- 18715389
TI  - Self-determination of patients with rheumatoid arthritis: model development
      during action research.
AB  - The purpose of this article is to describe the content and the development of the
      model to promote self-determination of patients with rheumatoid arthritis from a
      point of view of patients and nurses. For the patients the data were gathered
      using semistructured interviews and for the nurses through three focus groups in
      the initial and evaluation phases. The data were analysed by themes using
      qualitative content analysis. The model consisted of the concept of self
      determination, impediments to and preconditions for self-determination, promoting
      and focusing on consequences. Patient's activity was a new view of the concept.
      Impediments to self-determination were linked to limitations and preconditions to
      patients' freedom to express themselves. Support developed an important factor
      promoting self-determination. The results indicate a clear need for various types
      of supportive nursing care to promote self-participation in patient care.

PMID- 18715390
TI  - Exploring relationships in teenage pregnancy.
AB  - The aim of this paper is to report a study exploring aspects of teenage pregnant
      women relationships with the fathers of their unborn children within the context
      of two contrasting demographic areas of the UK. The perceptions of teenage
      pregnant women on how they view their relationship with the fathers of their
      unborn babies has not been fully investigated. Three major categories emerged
      from the perspectives of 47 teenage pregnant women: (i) age of baby's father;
      (ii) education and employment status of baby's father; and (iii) ability of
      baby's father to provide financial support. Teenage pregnant women living in the
      south-east were more likely to maintain the relationship with fathers of their
      babies than those living in the north-west. This was found to be statistically
      significant. The age, employment status and education of the baby's father can
      influence the continuance of the partnership between the participant and of the
      father of her baby. The statistical difference in the maintenance of the
      relationship between the prospective parents may be associated with the
      continuing demographic and cultural characteristics of the north-west, where
      teenage pregnancy remains high and the south-east where the rates are low.

PMID- 18715391
TI  - Automated versus manual blood pressure measurement: a randomized crossover trial.
AB  - This study evaluated the accuracy and reliability of the Dinamap 8100 automated
      blood pressure machine against three internationally recognized criteria.
      Systolic and diastolic blood pressures were taken concurrently by two nurses
      using the automated machine and a manual sphygmomanometer. Results demonstrated
      agreement between automated and manual readings on one set of criteria for both
      systolic and diastolic pressures, and support for systolic readings only on one
      other criterion. Comparison of mean differences between automated and manual
      measures showed the automated machine consistently under-read both systolic and
      diastolic blood pressures. The conclusion from this study was that the Dinamap
      8100 machine can be used with some degree of confidence to assess systolic blood
      pressures in a general population of adult hospital inpatients, but with caution
      when taking diastolic readings.

PMID- 18715392
TI  - Ritual: the final expression of care.
AB  - Hospice nurses know that all their patients will die. There are several potential
      benefits of including rituals and healing practices into the hospice care setting
      for staff. Evidence suggests that not only does it provide an outlet for hospice
      workers to express their grief and reflect on their work in an accepting
      environment; providing closure for their patient's passing but it has also been
      shown to decrease the risk of burnout and compassion fatigue. This article
      discusses the important aspects of grief rituals and provides an illustrative
      example of one such ritual.

PMID- 18715393
TI  - Personal resources supporting living at home as described by older home care
      clients.
AB  - This study describes the personal resources of older (> or = 75 years) home care
      clients in Finland and their perceptions of factors that enhance and constrain
      their ability to live independently at home. The data were collected by
      unstructured interviews with 21 older home care clients. Inductive content
      analysis were used to analyse the data. The resources of older people consisted
      of a sense of control over one's life and a determination to remain active.
      Factors enhancing older people's resources were their involvement in leisure
      activities and social networks, factors undermining their resources were
      conditions on living imposed by outsiders, declining health and loneliness. The
      results show that home care professionals do not yet have sufficient skills and
      abilities to identify and support older people's existing resources. As well as
      having access to necessary resources, it is also crucial that older people know
      how to use them.

PMID- 18715394
TI  - The effectiveness of a promotion programme on hand hygiene compliance and
      nosocomial infections in a neonatal intensive care unit.
AB  - This quasi-experimental study aimed to identify the impact of a promotion
      programme on hand hygiene practices and its effect on nosocomial infection rates
      in a neonatal intensive care unit of a university hospital in Thailand. The study
      populations were 26 nursing personnel. After implementing a hand hygiene
      promotion programme, compliance with hand hygiene among nursing personnel
      improved significantly from 6.3% before the programme to 81.2% 7 months after the
      programme. Compliance rate did not correlate with the intensity of patient care.
      Nosocomial infection rate did not decrease after the intervention, probably
      because of the multifactorial nature of infections. All participants agreed that
      promotion programme implemented in this project motivated them to practise better
      hand hygiene. This study indicated that multiple approaches and persistent
      encouragement are key factors leading to a sustained high level of appropriate
      hand hygiene practices among nursing personnel.

PMID- 18715395
TI  - Going the distance--experiences of women with gynaecological cancer residing in
      rural remote north Queensland.
AB  - Women who are diagnosed with gynaecological cancer face a difficult journey. For
      women residing in areas geographically removed from major health providers the
      journey can be much more difficult. While they 'make do' and 'struggle on', their
      lived experiences can provide valuable insight into the complex issues
      surrounding a cancer diagnosis in rural areas. This study aimed to understand
      their experiences through the women's stories and sought to identify the major
      themes impacting on these stories. This qualitative phenomenological study
      undertook interviews with seven women with gynaecological cancer who reside in
      rural and remote north Queensland. Analysis of the data collected revealed three
      themes: seeking answers at a distance; sharing information within a small
      community; and experiences of navigating the health system. The results show the
      inherent difficulties in accessing support in rural areas and the difficulties
      associated with travelling considerable distances to undergo treatment.

PMID- 18715396
TI  - At the European union's door: a Hungarian team's experiences of participating in
      the Project Leonardo for better nursing care.
AB  - The aim of this paper is to provide information about the work completed by
      Hungarian nurses and professors of baccalaureate nurses, in the framework of
      Leonardo project, organized and sponsored by the European Union. The goal of the
      project was to increase the effectiveness of chief nurses through a further
      training programme in the field of management. The team in Szeged (Hungary) chose
      as their area of interest, human resource management, as in this field, it is
      possible to achieve the greatest improvement with the smallest financial
      investment. We measured fluctuations and the absenteeism of nurses, changes in
      their qualifications, and nurse and patient satisfaction at the beginning and end
      of the period studied. Almost all parameters showed improvement by the end of the
      tested period. A book of two volumes (available on the WEB in English and in
      French) was prepared containing the recommendations of EU.

PMID- 18715397
TI  - Is sham acupuncture necessary?

PMID- 18715399
TI  - Eradication of Helicobacter pylori for the prevention of peptic ulcer rebleeding.

PMID- 18715401
TI  - A comparative study of standard vs. high definition colonoscopy for adenoma and
      hyperplastic polyp detection with optimized withdrawal technique.
AB  - BACKGROUND: Colonoscopy has a known miss rate for polyps and adenomas. High
      definition (HD) colonoscopes may allow detection of subtle mucosal change,
      potentially aiding detection of adenomas and hyperplastic polyps. AIM: To compare
      detection rates between HD and standard definition (SD) colonoscopy. METHODS:
      Prospective, cohort study with optimized withdrawal technique (withdrawal time >6
      min, antispasmodic, position changes, re-examining flexures and folds). One
      hundred and thirty patients attending for routine colonoscopy were examined with
      either SD (n = 72) or HD (n = 58) colonoscopes. RESULTS: Groups were well
      matched. Sixty per cent of patients had at least one adenoma detected with SD vs.
      71% with HD, P = 0.20, relative risk (benefit) 1.32 (95% CI 0.85-2.04). Eighty
      eight adenomas (mean +/- standard deviation 1.2 +/- 1.4) were detected using SD
      vs. 93 (1.6 +/- 1.5) with HD, P = 0.12; however more nonflat, diminutive (<6 mm)
      adenomas were detected with HD, P = 0.03. Twenty-three proximal hyperplastic
      polyps (0.32 +/- 0.58) were detected with SD vs. 31 (0.53 +/- 0.86) with HD, P =
      0.35. Overall prevalence of proximal large (>9 mm) hyperplastic polyps was 7%
      (0.09 +/- 0.36). CONCLUSIONS: High definition did not lead to a significant
      increase in adenoma or hyperplastic polyp detection, but may help where
      comprehensive lesion detection is paramount. High detection rates appear possible
      with either SD or HD, when using an optimized withdrawal technique.

PMID- 18715402
TI  - Assessing the impact of climate variation on survival in vertebrate populations.
AB  - The impact of the ongoing rapid climate change on natural systems is a major
      issue for human societies. An important challenge for ecologists is to identify
      the climatic factors that drive temporal variation in demographic parameters,
      and, ultimately, the dynamics of natural populations. The analysis of long-term
      monitoring data at the individual scale is often the only available approach to
      estimate reliably demographic parameters of vertebrate populations. We review
      statistical procedures used in these analyses to study links between climatic
      factors and survival variation in vertebrate populations. We evaluated the
      efficiency of various statistical procedures from an analysis of survival in a
      population of white stork, Ciconia ciconia, a simulation study and a critical
      review of 78 papers published in the ecological literature. We identified six
      potential methodological problems: (i) the use of statistical models that are not
      well-suited to the analysis of long-term monitoring data collected at the
      individual scale; (ii) low ratios of number of statistical units to number of
      candidate climatic covariates; (iii) collinearity among candidate climatic
      covariates; (iv) the use of statistics, to assess statistical support for
      climatic covariates effects, that deal poorly with unexplained variation in
      survival; (v) spurious detection of effects due to the co-occurrence of trends in
      survival and the climatic covariate time series; and (vi) assessment of the
      magnitude of climatic effects on survival using measures that cannot be compared
      across case studies. The critical review of the ecological literature revealed
      that five of these six methodological problems were often poorly tackled. As a
      consequence we concluded that many of these studies generated hypotheses but only
      few provided solid evidence for impacts of climatic factors on survival or
      reliable measures of the magnitude of such impacts. We provide practical advice
      to solve efficiently most of the methodological problems identified. The only
      frequent issue that still lacks a straightforward solution was the low ratio of
      the number of statistical units to the number of candidate climatic covariates.
      In the perspective of increasing this ratio and therefore of producing more
      robust analyses of the links between climate and demography, we suggest leads to
      improve the procedures for designing field protocols and selecting a set of
      candidate climatic covariates. Finally, we present recent statistical methods
      with potential interest for assessing the impact of climatic factors on
      demographic parameters.

PMID- 18715404
TI  - Five steps from evidence to effect: exercising clinical freedom to implement
      research findings.

PMID- 18715405
TI  - A randomised controlled trial comparing GnRH antagonist cetrorelix with GnRH
      agonist leuprorelin for endometrial thinning prior to transcervical resection of
      endometrium.
AB  - OBJECTIVES: To compare the effectiveness of leuprorelin and cetrorelix, when used
      as preoperative endometrial thinning agents prior to transcervical resection of
      endometrium (TCRE). DESIGN: A prospective, double-blind randomised controlled
      trial. SETTING: Gynaecological department of a UK district general hospital.
      PARTICIPANTS: A total of 106 premenopausal women with dysfunctional uterine
      bleeding, undergoing TCRE. INTERVENTIONS: Women were equally randomised to 3.75
      mg of leuprorelin acetate (3-4 weeks) or 3 mg cetrorelix (4-7 days) prior to
      TCRE. About 1 ml saline was given as placebo in both arms. MAIN OUTCOME MEASURES:
      Amenorrhoea rate at 6 months, endometrial thickness using transvaginal ultrasound
      on the day of operation. RESULTS: A total of 100 women completed the trial with
      no loss to follow up. Amenorrhoea rate at 6 months after surgery was high in both
      groups (80% cetrorelix and 84% leuprorelin) with no statistical significance. All
      endometrial outcome measures including endometrial thickness on ultrasound,
      histology and operative appearance were more favourable in leuprorelin group as
      compared with cetrorelix (P values 0.013, <0.001 and 0.003 respectively). More
      women in leuprorelin group had hot flushes as compared with cetrorelix (15/50
      versus 6/50; P = 0.047). No significant differences were seen in other outcome
      measures. CONCLUSIONS: In dosages used, leuprorelin produced more consistent
      thinning of the endometrium as compared with cetrorelix, although this did not
      make any significant difference to operative or menstrual outcomes. The
      endometrial thinning effect with cetrorelix does appear to be more favourable
      than that seen at postmenstrual phase in other studies. The optimum (possibly
      higher) dosage of cetrorelix for this purpose has not yet been established.

PMID- 18715406
TI  - Mannose-binding lectin gene polymorphism and resistance to therapy in women with
      recurrent vulvovaginal candidiasis.
AB  - PRECIS: Women with recurrent vulvovaginal candidiasis (RVC) due to a polymorphism
      in codon 54 of the MBL2 gene respond better to fluconazole maintenance therapy
      than do women with other underlying causes. OBJECTIVE: To explain differences in
      response rates to maintenance therapy with fluconazole in women suffering from
      RVC by evaluating associations with a polymorphism in the gene coding for mannose
      binding lectin (MBL). DESIGN: Follow-up study, neted case-control group. SETTING:
      Women attending vulvoginitis clinic for RVC. POPULATION: Women participating in a
      multicentric study in Belgium with a degressive dose of fluconazole for RVC (the
      ReCiDiF trial) were divided into good responders, intermediate responders and
      nonresponders according to the number of relapses they experienced during
      therapy. From 109 of these women with adequate follow-up data, vaginal lavage
      with 2 ml of saline were performed at the moment of a proven acute attack at
      inclusion in the study, before maintenance treatment was started. A buccal swab
      was obtained from 55 age-matched women without a history of Candida infections,
      serving as a control group. METHODS: Extracted DNA from buccal or vaginal cells
      was tested for codon 54 MBL2 gene polymorphism by polymerase chain reaction and
      endonuclease digestion. MAIN OUTCOME MEASURES: Frequency of MBL2 condon 54 allele
      B in women with optimal or poor response to maintenance therapy in composition
      with controls. Results Women (n = 109) suffering from RVC were more likely to
      carry the variant MBL2 codon 54 allele B than control women (20 versus 6.6%, OR
      3.4 [95% CI 1.3-8.2], P = 0.01). B alleles were present in 25% of the 36 women
      not suffering from any recurrence during the maintenance therapy with decreasing
      doses of fluconazole (OR 4.9 [95% CI 1.9-12.5], P = 0.0007 versus controls), in
      20% of the 43 women with sporadic recurrences (OR 3.6 [95% CI 1.4-9.2], P = 0.007
      versus controls) and in 15% of the 30 women who had to interrupt the treatment
      regimen due to frequent relapses (P = 0.097 versus controls). CONCLUSIONS: The
      MBL2 codon 54 gene polymorphism is more frequent in Belgian women suffering from
      RVC than in controls. The presence of the B allele is associated with a superior
      response to fluconazole maintenance therapy as compared with RVC patients without
      this polymorphism. We conclude that RVC due to deficient MBL production is more
      easily helped with antifungal medication than is RVC due to some other mechanism.

PMID- 18715407
TI  - A randomised comparison of vaginoscopic office hysteroscopy and saline infusion
      sonography: a patient compliance study.
AB  - OBJECTIVE: The purpose of this study was to compare patient discomfort during
      saline infusion sonography (SIS) and office hysteroscopy performed according to a
      vaginoscopic approach. DESIGN: Randomised controlled trial. SETTING: University
      hospital. POPULATION: Women with an indication for further investigation of the
      uterine cavity. METHODS: A total of 100 women randomly allocated to either SIS or
      vaginoscopic office hysteroscopy in an outpatient clinic. MAIN OUTCOME MEASURES:
      Scores on a visual analogue scale (VAS) for pain and a present pain intensity
      (PPI) scale, conclusiveness and success rate. RESULTS: The patients' pain scores
      on both the VAS and the PPI were lower for SIS when compared with office
      hysteroscopy (P < 0.05). However, in cases of severe pain (VAS > 7 or PPI > 2),
      there was no statistically significant difference between both groups. The
      success rate, defined as adequate inspection of the cervical canal and uterine
      cavity, was 94% for SIS compared with 92% for office hysteroscopy (P = 0.633).
      SIS, multiparity, shorter procedure time and position of the uterus in
      anteversion decreased pain scores among women studied. CONCLUSIONS: Both SIS and
      office hysteroscopy are successful procedures and well tolerated by women. SIS
      induces significantly less discomfort than office hysteroscopy and should
      therefore be considered the method of choice.

PMID- 18715408
TI  - Effect of margin status on cervical intraepithelial neoplasia recurrence
      following LLETZ in women over 50 years.
AB  - OBJECTIVE: To establish the effect of margin status on recurrence following large
      loop excision of the transformation zone (LLETZ) in women over 50 years. STUDY
      DESIGN: Prospectively collected data of women over 50 years, who underwent LLETZ
      for suspected cervical intraepithelial neoplasia between 1998 and 2003, were
      analysed. Women were followed up for up to over 6 years. SETTING: District
      colposcopy service based at a gynae-oncology cancer centre. MAIN OUTCOME
      MEASURES: The main outcome measure included histologically detected recurrence.
      Any abnormal cytology on follow up was also documented. METHODS: Prospectively
      collected data were analysed from the colposcopy database. Recurrence was
      analysed using Kaplan-Meir plots and Cox regression. Fisher's exact test was used
      to determine the association between margins and grade. The Kruskal-Wallis and
      Mann-Whitney U tests were used to compare age and duration of follow up between
      groups. RESULTS: A total of 118 women underwent LLETZ and 92 were included in the
      final analysis. Margins were designated as clear (n = 62), involved (n = 22) or
      uncertain (n = 8). Histological recurrence occurred in 12 while abnormal cytology
      was demonstrated in 17 women. One woman with involved margins developed cervical
      cancer. Individuals with clear margins were less likely to have recurrence than
      those with involved margins (Hazard Ratio (HR) 0.18, 95% CI: 0.06-0.59). Involved
      margins were more common with high-grade than low-grade lesions (P = 0.002).
      CONCLUSION: The data show an association between disease recurrence and the
      finding of involved margins in this cohort.

PMID- 18715409
TI  - Transgenerational effects of prenatal exposure to the Dutch famine on neonatal
      adiposity and health in later life.
AB  - OBJECTIVE: Maternal undernutrition during gestation is associated with increased
      metabolic and cardiovascular disease in the offspring. We investigated whether
      these effects may persist in subsequent generations. DESIGN: Historical cohort
      study. SETTING: Interview during a clinic or home visit or by telephone.
      POPULATION: Men and women born in the Wilhelmina Gasthuis in Amsterdam between
      November 1943 and February 1947. METHODS: We interviewed cohort members (F1) born
      around the time of the 1944-45 Dutch famine, who were exposed or unexposed to
      famine in utero, about their offspring (F2). MAIN OUTCOME MEASURES: Birthweight,
      birth length, ponderal index and health in later life (as reported by F1) of the
      offspring (F2) of 855 participating cohort members, according to F1 famine
      exposure in utero. RESULTS: F1 famine exposure in utero did not affect F2 (n =
      1496) birthweight, but, among the offspring of famine-exposed F1 women, F2 birth
      length was decreased (-0.6 cm, P adjusted for F2 gender and birth order = 0.01)
      and F2 ponderal index was increased (+1.2 kg/m(3), P adjusted for F2 gender and
      birth order = 0.001). The association remained unaltered after adjusting for
      possible confounders. The offspring of F1 women who were exposed to famine in
      utero also had poor health 1.8 (95% CI 1.1-2.7) times more frequently in later
      life (due to miscellaneous causes) than that of F1 unexposed women. CONCLUSIONS:
      We did not find transgenerational effects of prenatal exposure to famine on
      birthweight nor on cardiovascular and metabolic disease rates. F1 famine exposure
      in utero was, however, associated with increased F2 neonatal adiposity and poor
      health in later life. Our findings may imply that the increase in chronic disease
      after famine exposure in utero is not limited to the F1 generation but persists
      in the F2 generation.

PMID- 18715410
TI  - Cerebral palsy and restricted growth status at birth: population-based case
      control study.
AB  - OBJECTIVE: To evaluate the association between growth status at birth and
      subsequent development of cerebral palsy in preterm and term infants. DESIGN:
      Population-based case-controlled study. SETTING: Cerebral palsy register in
      Western Sweden. Subjects Cohort of 334 singletons born between 1983 and 1990,
      with cerebral palsy diagnosed from age 4, and 668 singletons matched for
      gestation, gender and delivery unit. METHOD: Growth status at birth was
      determined using small for gestational age (SGA) categories, with customised
      birthweight percentiles (SGAcust) based on the Swedish population. MAIN OUTCOME
      MEASURES: Proportion of babies that were SGAcust, comparing cases and controls in
      three gestational age categories: early preterm (24-33 weeks), late preterm (34
      36 weeks) and term (37+ weeks). RESULTS: Of the 334 children with cerebral palsy,
      87 (26.6%) were born early preterm, 27 (8.1%) late preterm and 218 (66%) at term.
      Children who had been born at term were more likely to have been SGA <1st
      customised percentile (SGAcust1) than their matched controls (OR 6.6, 95% CI 2.3
      18.6). In contrast, children with cerebral palsy born preterm were not more
      likely to have been SGAcust1 (OR 0.9, 95% CI 0.4-1.9), and this applied to early
      preterm as well as late preterm births. For less severely small babies (SGA
      between 1st and 5th customised percentiles), the association with cerebral palsy
      remained significant for term births (OR 5.2, 95% CI 2.7-10.1) but was again not
      significant for preterm births. CONCLUSIONS: Term singletons with severely SGA
      birthweights had a five- to seven-fold risk of developing cerebral palsy compared
      with gestational age-matched infants with birthweights within normal limits. For
      children born preterm, SGA was not more likely to be present in cases than in
      controls. These findings support the concept of cerebral palsy as a
      multifactorial condition and highlight the importance of antenatal surveillance
      of fetal growth.

PMID- 18715411
TI  - Should parity be included in customised fetal weight standards for identifying
      small-for-gestational-age babies? Results from a French multicentre study.
AB  - OBJECTIVE: Parity is one of several parameters used to customise fetal growth
      norms. However, it is uncertain whether the lower birthweight of babies born to
      primiparous women reflects physiological or pathological variation. Our aim was
      to assess the impact of adjusting for parity in identification of small-for
      gestational-age (SGA) births. DESIGN: Comparison of two customised definitions of
      SGA with and without parity. SETTING: Routinely collected data in five tertiary
      maternity hospitals in France. POPULATION: A total of 51 126 singleton births
      without malformations from 1997 to 2002. METHODS: Characteristics of mothers and
      babies and adverse pregnancy outcomes for SGA and non-SGA births were compared
      using customised definitions with and without parity. MAIN OUTCOME MEASURES:
      Neonatal morbidity and mortality. RESULTS: SGA births among primiparas increased
      from 14.9 to 18.0% when parity was excluded. Overall rates of SGA rose from 14.4
      to 15.0%. Newly defined cases of SGA were babies of primiparas. They had higher
      rates of admission to a neonatal unit and caesarean section than babies
      reclassified as non-SGA. Perinatal mortality was 9.1 per thousand (parity
      included) and 9.7 per thousand (parity excluded) and did not differ significantly
      from babies classified as non-SGA by both standards (5.4 per thousand).
      CONCLUSIONS: Adjustment for parity markedly decreased the proportion of
      primiparas diagnosed with SGA babies but did not appear to improve the
      identification of high-risk babies. Removing parity would simplify the customised
      definition of SGA and would eliminate the need for the assumption that lower
      birthweight for primiparous women is normal.

PMID- 18715412
TI  - Prevalence and risk factors of severe obstetric haemorrhage.
AB  - OBJECTIVE: To determine the prevalence, causes, risk factors and acute maternal
      complications of severe obstetric haemorrhage. DESIGN: Population-based registry
      study. POPULATION: All women giving birth (307,415) from 1 January 1999 to 30
      April 2004 registered in the Medical Birth Registry of Norway. Information about
      socio-economic risk factors was obtained from Statistics Norway. METHODS: Cross
      tabulation was used to study prevalence, causes and acute maternal complications
      of severe obstetric haemorrhage. Associations of severe obstetric haemorrhage
      with demographic, medical and obstetric risk factors were estimated using
      multiple logistic regression models. MAIN OUTCOME MEASURE: Severe obstetric
      haemorrhage (blood loss of > 1500 ml or blood transfusion). RESULTS: Severe
      obstetric haemorrhage was identified in 3501 women (1.1%). Uterine atony,
      retained placenta and trauma were identified causes in 30, 18 and 13.9% of women,
      respectively. The demographic factors of a maternal age of > or =30 years and
      South-East Asian ethnicity were significantly associated with an increased risk
      of haemorrhage. The risk was lower in women of Middle Eastern ethnicity, more
      than three and two times higher for emergency caesarean delivery and elective
      caesarean than for vaginal birth, respectively, and substantially higher for
      multiple pregnancies, von Willebrand's disease and anaemia (haemoglobin <9 g/dl)
      during pregnancy. Admissions to an intensive care unit, postpartum sepsis,
      hysterectomy, acute renal failure and maternal deaths were significantly more
      common among women with severe haemorrhage. CONCLUSION: The high prevalence of
      severe obstetric haemorrhage indicates the need to review labour management
      procedures. Demographic and medical risk factors can be managed with extra
      vigilance.

PMID- 18715413
TI  - Evidence of early first-trimester growth restriction in pregnancies that
      subsequently end in miscarriage.
AB  - OBJECTIVES: To examine whether viable early pregnancies that subsequently end in
      miscarriage exhibit evidence of first-trimester growth restriction. DESIGN:
      Prospective cohort study. SETTING: Early pregnancy unit (EPU) of a teaching
      hospital. POPULATION: Women attending EPU between 5 and 10 weeks of gestation.
      METHODS: Women with spontaneously conceived intrauterine, viable singleton
      pregnancies with certain last menstrual period and regular cycles were included.
      The deviation between the observed and expected crown-rump length (CRL) for
      gestation was calculated and expressed as a z score. Pregnancies were followed up
      until the 11-14 week scan, and the deviation between those that remained viable
      and miscarried subsequently was calculated. MAIN OUTCOME MEASURES: Viability at
      11-14 week scan. RESULTS: Over 6 months, 316 women met the inclusion criteria.
      Twenty-four (7.4%) women were excluded. Of the remaining 292, the pregnancy
      remained viable in 251 (86%) and 41 (14%) suffered a miscarriage. At the first
      transvaginal ultrasound, the z score of the mean measured CRL for pregnancies
      that remained viable was -0.82, SD 1.46, while in pregnancies that subsequently
      miscarried the z score was -2.42 and the CRL was significantly smaller, SD 1.31
      (P < 0.0001). In the latter group, the initial CRL was below the expected mean
      for gestational age in all women, while in 61% (25/41), the CRL was at least 2
      SDs below the expected mean. CONCLUSIONS: CRL was significantly smaller in
      pregnancies that subsequently ended in miscarriage. This suggests that early
      first-trimester growth restriction is associated with subsequent intrauterine
      death.

PMID- 18715414
TI  - Induction of labour in nulliparous and multiparous women: a UK, multicentre, open
      label study of intravaginal misoprostol in comparison with dinoprostone.
AB  - OBJECTIVE: To compare the efficacy and safety of a 25-microgram vaginal tablet of
      misoprostol (APL202) with dinoprostone (3-mg vaginal tablet) in cervical ripening
      and labour induction. DESIGN: A randomised, open-label, noninferiority,
      comparative study in two maternal populations. SETTING: Eighteen NHS study
      centres across the UK. POPULATION: Nulliparous or multiparous women with a
      singleton pregnancy eligible for induction of labour. METHODS: Women were
      randomised to receive either misoprostol, initially 25 micrograms (50 micrograms
      in nulliparous women with Bishop score < or =4) followed by 25 micrograms after 4
      and 8 hours, or dinoprostone, initially 3 mg followed by 3 mg after 6 hours.
      Clinical noninferiority of misoprostol was defined as an absolute difference
      between treatments of no more than 10% for the primary outcome. MAIN OUTCOME
      MEASURES: The number of vaginal deliveries achieved within 24 hours of labour
      induction. Maternal and fetal safety outcomes. RESULTS: A total of 626 women were
      randomised to misoprostol (n = 318) or dinoprostone (n = 308) treatment. The rate
      of vaginal deliveries achieved within 24 hours of induction did not significantly
      differ between the misoprostol and dinoprostone (43 versus 47%; 3.74% difference,
      95% CI -3.58 to 11.05, respectively) treatment groups. The treatments were
      generally comparable for other secondary efficacy measures. Maternal and fetal
      adverse events were similarly distributed across the misoprostol and dinoprostone
      groups. CONCLUSIONS: Low-dose misoprostol is efficacious in cervical ripening and
      labour induction and demonstrates a similar fetal and maternal safety profile to
      dinoprostone.

PMID- 18715415
TI  - A randomised controlled trial of early versus delayed oxytocin augmentation to
      treat primary dysfunctional labour in nulliparous women.
AB  - BACKGROUND: Oxytocin is widely used to speed up slow labour, especially in
      nulliparous women, but randomised trials, apart from one reported only in
      abstract, have been too small to exclude important effects. OBJECTIVE: To test
      the hypothesis that early use of oxytocin reduces the need for caesarean
      delivery. DESIGN: A randomised controlled trial. SETTING: Twelve obstetric units
      within the Northern and Yorkshire regions in the North East of England.
      PARTICIPANTS: A total of 412 low-risk nulliparous women in spontaneous labour at
      term, who had been diagnosed with primary dysfunctional labour were recruited
      from January 1999 to December 2001. INTERVENTION: Immediate oxytocin
      administration (active group) or oxytocin withheld for up to 8 hours
      (conservative group). MAIN OUTCOME MEASURES: Caesarean section and operative
      vaginal delivery rates. The length of labour measured from the time of
      randomisation to delivery. The rate of maternal Edinburgh Postnatal Depression
      Scale (EPDS) greater than 12 (major depression) within 48 hours of delivery.
      RESULTS: The caesarean section rates were 13.5% active versus 13.7% controls (OR
      0.98, 95% CI 0.6-1.7). Operative delivery, 24.5% versus 30.9% (OR 0.73, 95% CI
      0.5-1.1). The median (interquartile range) randomisation to delivery interval in
      the active group was 5 hours 52 minutes (3:57-8:28) and in the conservative group
      9 hours 8 minutes (5:06-13:16) (P < 0.001). The rate of EPDS >12 was 20% in the
      active arm versus 15% among controls (OR 1.26, 95% CI 0.7-2.2). There was one
      perinatal death in each group and no major differences in perinatal outcomes.
      CONCLUSIONS: Among nulliparous women with primary dysfunctional labour, early use
      of oxytocin does not reduce caesarean section or short-term postnatal depression.
      However, it shortens labour considerably and may reduce operative vaginal
      deliveries.

PMID- 18715416
TI  - Serious toxicity associated with continuous nevirapine-based HAART in pregnancy.
AB  - OBJECTIVE: This study was designed to determine the safety of nevirapine (NVP)
      based highly active antiretroviral therapy (HAART) in a cohort of HIV-positive
      pregnant women. DESIGN: This was a prospective cohort study of HIV-positive
      pregnant women. POPULATION AND SETTING: All HIV-positive women treated with HAART
      during pregnancy from January 1997 to February 2004 at the British Columbia (BC)
      Women's Hospital in Vancouver, BC, Canada. METHODS: Demographic and clinical data
      were collected to compare antiretroviral drug toxicities in women treated
      antenatally with NVP-based or non-NVP-based HAART. Multivariate analyses were
      then used to investigate determinants of toxicity. RESULTS: From 1997 to 2004,
      103 HIV-positive pregnant women received HAART. Equivalent numbers of women were
      initially treated with NVP-based (54%) and non-NVP-based (46%) HAART. The groups
      did not differ by clinical or demographic parameters and duration of HAART
      exposure was similar between groups. Toxicities necessitating treatment
      discontinuation were observed in 6 of 56 NVP-exposed women (2 cases each of grade
      2, 3, and 4 toxicity) compared with 1 of 47 in the non-NVP-exposed women. First
      time use of NVP approached significance as a predictor for toxicity, with a
      toxicity rate of 12.5% (6/48) observed among those taking NVP for the first time
      (adjusted OR 2.68, 95% CI 0.49-14.6). CONCLUSION: Continuous NVP use in pregnancy
      resulted in a relatively higher rate of toxicity, and all cases of NVP toxicity
      occurred in women exposed to NVP for the first time during pregnancy.

PMID- 18715417
TI  - Documentation of simulated shoulder dystocia: accurate and complete?
AB  - OBJECTIVE: To investigate completeness and accuracy of record keeping by
      comparison of documentation and actual events, recorded on video and through a
      force-monitoring device, during simulated shoulder dystocia. DESIGN: An
      observational study. SETTING: Six maternity units in South West of England.
      POPULATION: Seventy-one midwives and 39 doctors. METHODS: Doctors and midwives
      documented their management of a shoulder dystocia simulation on paper used in
      their hospital (simple notepaper or preformatted form). Documentation was
      compared with video recording of each simulation and an electronic record of
      force applied during delivery. MAIN OUTCOME MEASURES: Documentation of head-to
      body delivery time (and comparison with actual delivery time). Documentation of
      force (and comparison with actual applied force). RESULTS: A total of 110
      participants documented their actions, 70.9% used a preformatted sheet, 29.1%
      used hospital notepaper. Fifty-six percent documented head-to-body delivery
      interval (HBDI) with 56% overestimating the time by more than 1 minute. Force
      used during the simulation was documented by 70.9%, with no relationship between
      the subjective description of force applied and the maximum recorded force. The
      anterior shoulder was documented by 78.2% and correctly identified in 80%.
      Documentation of force was more likely if a preformatted sheet was used (88
      versus 53%, P = 0.016). Documentation of the laterality of the anterior shoulder
      was tended to be more accurate with plain hospital notepaper (93 versus 78%, P =
      0.3526). CONCLUSIONS: Manoeuvres performed were well documented. HBDI and force
      applied were not documented accurately in the majority of simulated deliveries.
      Use of a preformatted sheet appeared to improve completeness, but not accuracy,
      of documentation.

PMID- 18715418
TI  - Termination of pregnancy according to immigration status: a population-based
      registry linkage study.
AB  - OBJECTIVE: Frequency of termination of pregnancy (TOP) and associated risk
      factors according to immigration status were studied. DESIGN: Population-based
      registry study linking hospital data with information from the Central Population
      Registry of Norway. SETTING: Oslo, Norway. POPULATION: All women 15-49 years
      undergoing TOP and resident in Oslo, Norway from 1 January 2000 to 31 July 2003.
      METHODS: TOP rates per 1000 women/year were calculated. The association of socio
      economic variables such as maternal age, marital status, number of children and
      education level within the study groups were estimated as odds ratios and using
      logistic regression. MAIN OUTCOME MEASURE: Termination of pregnancy. RESULTS:
      Refugees (30.2, 95% CI = 28.5-31.8) and labour migrants (19.9, 95% CI = 18.7
      21.3) had significantly higher TOP rates than nonmigrants (16.7, 95% CI = 16.3
      17.1). Except in women less than 25 years, labour migrants had higher TOP rates
      than nonmigrants. Refugees had the highest rates in all age groups. Being
      unmarried was associated with a substantially increased risk of TOP among the
      nonmigrants; such effect was not observed among labour migrants and refugees. Two
      or more children were associated with increased risk among nonmigrants and
      refugees compared with four or more among the labour migrants. Generally, higher
      education showed a protective effect that was most pronounced among nonmigrants.
      Compared with nonmigrants, adjusted risk of TOP was 1.37 (95% CI = 1.25-1.50) for
      labour migrants and 1.94 (95% CI = 1.79-2.11) for refugees. CONCLUSION: Public
      health efforts to increase the use of contraceptives among refugees and labour
      migrants above 25 years should be encouraged.

PMID- 18715419
TI  - Transumbilical surgical specimen retrieval: a viable refinement of laparoscopic
      surgery for pelvic masses.
AB  - The purpose of this study was to evaluate the feasibility and surgical outcome of
      a policy of routine specimen retrieval through the umbilical port, avoiding the
      enlargement of ancillary port-site incisions. A total of 1116 women underwent
      laparoscopic surgery for the treatment of a pelvic mass with extraction of the
      specimen through the umbilical port site (a total of 1453 retrieval procedures).
      All retrieval procedures were successfully carried out with this technique.
      Neither intraoperative complication related to the retrieval procedure nor
      accidental rupture of the endoscopic bag occurred. There was an injury to the
      epigastric artery. Neither trocar-site hernias (both umbilical trocar insertion
      sites and extraumbilical sites) nor port-site metastases occurred.

PMID- 18715420
TI  - An estimation of intrapartum-related perinatal mortality rates for booked home
      births in England and Wales between 1994 and 2003.

PMID- 18715421
TI  - Costing magnetic resonance-guided focused ultrasound surgery, a new treatment for
      symptomatic fibroids.

PMID- 18715422
TI  - Substandard care in maternal mortality due to hypertensive disease in pregnancy
      in the Netherlands.

PMID- 18715425
TI  - The risk of unexplained antepartum stillbirth in second pregnancies following
      caesarean section in the first pregnancy.

PMID- 18715426
TI  - The risk of unexplained antepartum stillbirth in second pregnancies following
      caesarean section in the first pregnancy.

PMID- 18715430
TI  - Trends in management and outcome of pregnancies in HIV-infected women in the UK
      and Ireland, 1990-2006.

PMID- 18715431
TI  - Blood pressure measurement in pregnancy.

PMID- 18715432
TI  - The value of the short-term fetal heart rate variation for timing the delivery of
      growth-retarded fetuses.
AB  - OBJECTIVE: To assess the clinical value of the short-term fetal heart rate
      variation (STV) for timing the delivery of severely growth-retarded fetuses, many
      associated with pre-eclampsia. DESIGN: Retrospective cohort study. SETTING: John
      Radcliffe Maternity Hospital, Oxford, UK. POPULATION: Two hundred and fifty-seven
      fetuses with a birthweight less than third percentile and a last computerised
      cardiotocography performed within 24 h of delivery. METHODS: Analysis of the
      relationship between antepartum STV and the perinatal outcome. MAIN OUTCOME
      MEASURES: Stillbirth rate and the acid-base status at birth. RESULTS: There were
      no stillbirths or neonatal deaths (NNDs) within 24 h in the study population.
      Decreasing STV was correlated with earlier deliveries (P < 0.001), lower
      birthweight (P < 0.001), lower umbilical artery pH at birth (P < 0.001), worse
      acid-base status at birth (P < 0.001) and worse postnatal outcome (P < 0.002).
      The STV was able to predict the presence or absence of acidaemia and metabolic
      acidaemia (area under the receiver operating characteristic curve 0.70 and 0.75,
      respectively, P < 0.001). The risk of metabolic acidaemia increased as the
      antepartum STV decreased, the optimum cutoff level being < or = 3.0 milliseconds
      (positive and negative predictive values 64.6 and 86.6%). An STV < or = 3.0
      milliseconds was associated with markedly higher rate of metabolic acidaemia and
      early NNDs compared with an STV > 3.0 milliseconds (54.2 versus 10.5% and 8.3
      versus 0.5%, respectively; P < 0.001). The deaths of the former group were all
      due to extreme prematurity and very low birthweight. CONCLUSIONS: The antepartum
      STV is an important marker of perinatal outcome in severely growth-retarded
      fetuses. Timing the delivery of the most preterm and small fetuses remains a
      difficult task.

PMID- 18715433
TI  - Inter-arm blood pressure differences in pregnant women.
AB  - OBJECTIVE: To determine the prevalence of blood pressure inter-arm difference
      (IAD) in early pregnancy and to investigate its possible association with
      maternal characteristics. DESIGN: A cross-sectional observational study. SETTING:
      Routine antenatal visit in a university hospital. POPULATION: A total of 5435
      pregnant women at 11-14 weeks of gestation. METHODS: Blood pressure was taken
      from both arms simultaneously with a validated automated device. MAIN OUTCOME
      MEASURES: The presence of inter-arm blood pressure difference of 10 mmHg or more.
      RESULTS: The IAD in systolic and diastolic blood pressure was 10 mmHg or more in
      8.3 and 2.3% of the women, respectively. Systolic IAD was found to be
      significantly related to systolic blood pressure and pulse pressure, and
      diastolic IAD was found to be significantly related to maternal age, diastolic
      blood pressure and pulse pressure. The systolic and diastolic IAD were higher in
      the hypertensive group compared with the normotensive group and absolute IAD
      increased with increasing blood pressure. About 31.0 and 23.9% of cases of
      hypertension would have been underreported if the left arm and the right arm were
      used, respectively, in measuring the blood pressure. CONCLUSIONS: There is a
      blood pressure IAD in a significant proportion of the pregnant population, and
      its prevalence increases with increasing blood pressure. By measuring blood
      pressure only on one arm, there is a one in three chance of underreporting
      hypertension. Therefore, it would be prudent that during the booking visit blood
      pressure should be taken in both arms and thus provide guidance for subsequent
      blood pressure measurements during the course of pregnancy.

PMID- 18715434
TI  - Cocoa butter lotion for prevention of striae gravidarum: a double-blind,
      randomised and placebo-controlled trial.
AB  - OBJECTIVE: To assess whether application of cocoa butter lotion reduces the
      development of striae gravidarum (SG). DESIGN: Multicentre, double-blind,
      randomised and placebo-controlled trial. SETTING: Beirut and Tripoli, Lebanon.
      POPULATION: Nulliparous women presenting for prenatal care. METHODS: Nulliparous
      women presenting in the first trimester were randomly assigned to receive a
      lotion containing cocoa butter or a placebo lotion. Women were instructed to
      apply the assigned lotion daily until delivery. MAIN OUTCOME MEASURE: The
      development of striae over the abdomen, breasts and thighs postpartum. RESULTS:
      Of 210 women enrolled, 175 (83%) completed the study. Ninety-one women received
      the study lotion and 84 received the placebo. There was no difference in the
      development of SG (45.1% versus 48.8%; P = 0.730) or the severity of SG between
      cases and controls. The results did not change when presence of stretch marks at
      enrolment or compliance with the regimen were taken into account. CONCLUSION:
      Topical application of a lotion containing cocoa butter does not appear to reduce
      the likelihood of developing striae gravidarum.

PMID- 18715435
TI  - Transcutaneous electrical nerve stimulation to treat vestibulodynia: a randomised
      controlled trial.
AB  - OBJECTIVE: To assess the efficacy of transcutaneous electrical nerve stimulation
      (TENS) in the treatment of vestibulodynia. DESIGN: Double-arm randomised placebo
      controlled trial. SETTING: An outpatient department for vulval disease.
      POPULATION: Forty women with vestibulodynia, a vestibular discomfort mostly
      reported as a burning pain, occurring in the absence of relevant visible findings
      or a specific, clinically identifiable, neurological disorder. METHODS: Twice a
      week active TENS or sham treatment were delivered through a vaginal probe via a
      calibrated dual channel YSY-EST device. Women of both groups underwent 20
      treatment sessions. MAIN OUTCOME MEASURES: Visual analogue scale (VAS), the short
      form of the McGill-Melzack Pain Questionnaire (SF-MPQ), the Marinoff Scale for
      dyspareunia and the Female Sexual Function Index questionnaire (FSFI) were
      assessed at baseline, at the end of treatment and at follow up 3 months after the
      end of treatment. RESULTS: The VAS and SF-MPQ scores (6.2 +/- 1.9 and 19.5 +/-
      11.9 before treatment, respectively) improved significantly in the active TENS
      group (2.1 +/- 2.7, P= 0.004 and 8.5 +/- 10.7, P= 0.001, respectively), but not
      in the placebo group. The Marinoff dyspareunia scale and the FSFI also showed a
      significant improvement. CONCLUSIONS: TENS is a simple, effective and safe short
      term (3 months) treatment for the management of vestibulodynia.

PMID- 18715436
TI  - High isoprostane level in cardinal ligament-derived fibroblasts and urine sample
      of women with uterine prolapse.
AB  - We studied the isoprostane level, a well-recognised biomarker of oxidative
      stress, from women with uterine prolapse and age-matched female controls without
      prolapse. Cardinal ligament-derived fibroblasts explanted from women with
      prolapse showed a significant increased level of isoprostane production (P <
      0.05) compared with those derived from controls. This concurs with elevated
      urinary isoprostane levels identified among women with prolapse (P < 0.001)
      compared with controls. In addition, the matrix metalloproteinase 2 mRNA was
      significantly increased (P= 0.004) among women with uterine prolapse. Parallel
      findings of increased isoprostane in cardinal ligament and urine sample among
      women with prolapse suggest that oxidative stress might be involved in the
      development of uterine prolapse.

PMID- 18715438
TI  - Uncertainty around home birth transfers.

PMID- 18715439
TI  - An estimation of intrapartum-related perinatal mortality rates for booked home
      births in England and Wales between 1994 and 2003. Editor-in-Chief's reply.

PMID- 18715440
TI  - Risk of intrapartum-related perinatal mortality in booked home births.

PMID- 18715442
TI  - Data of Dutch homebirths needs rectification.

PMID- 18715444
TI  - Comparison of self-administered vaginal misoprostol versus placebo for cervical
      ripening prior to operative hysteroscopy using a sequential trial design.

PMID- 18715446
TI  - Comparison of self-administered vaginal misoprostol versus placebo for cervical
      ripening prior to operative hysteroscopy using a sequential trial design.

PMID- 18715448
TI  - Anaesthetic choice in the colposcopy clinic: a retrospective analysis of
      routinely collected data.

PMID- 18715450
TI  - Immediate cord clamping may increase neonatal acidaemia.

PMID- 18715451
TI  - Costing magnetic resonance guided focused ultrasound surgery.

PMID- 18715452
TI  - The MDRD formula in pregnancy.

PMID- 18715455
TI  - Congenital heart disease--Medline/Pubmed indexing.

PMID- 18715456
TI  - A risk adjusted method for comparing adverse outcomes among practitioners in
      pediatric and congenital cardiac catheterization.
AB  - OBJECTIVE: We sought to develop a method to adjust for case mix diversity and
      allow comparison of adverse outcome rates among practitioners in pediatric and
      congenital cardiac catheterization. PATIENTS AND METHODS: A single institutional
      database that captured demographic and procedural data was used to identify
      patient and procedural characteristics associated with adverse events (AE) and
      any high severity event classified as preventable or possibly preventable (P/PP).
      Diagnostic and procedural risk groups were created and indicators of hemodynamic
      vulnerability were defined. Expected event rates by the practitioners adjusting
      for case mix were calculated. Standardized adverse event ratios (SAER), defined
      as the observed rate divided by the expected rate for each practitioner were
      calculated with 95% confidence intervals. RESULTS: The database included 1727
      hemodynamic (30%) and interventional (70%) cases performed by seven practitioners
      in 18 months. During 147 cases, at least one P/PP AE occurred; among the seven
      practitioners observed, event rates ranged from 3.2 to 14.2%. In multivariable
      analysis, risk factors for all P/PP events included highest procedure risk group
      (odds ratio [OR] 2.1 for group 2, and 2.8 for group 3, relative to group 1, P =
      .001 and P < .001, respectively) and weight less than 4 kg (OR 2.8, P < .001).
      High severity P/PP events occurred in 67 cases with rates ranging from 2.0 to
      6.6% by the practitioners. For these events, risk factors included: highest
      procedure risk group (OR 4.5 for group 2, and 4.9 for group 3, both P < .001) and
      an indicator of hemodynamic vulnerability (OR 1.8, P = .026). For the seven
      practitioners, the SAER ranged from 0.41 to 1.32 for any P/PP AE and from 0.69 to
      1.44 for P/PP high severity events. In this cohort, we did not identify any
      statistically significant performance differences. CONCLUSION: Despite wide
      variations in case mix complexity in pediatric and congenital cardiac
      catheterization, this study demonstrates a method for risk adjustment which
      allows equitable comparisons among practitioners at a single institution.

PMID- 18715457
TI  - Midterm outcome of stent dilatation of patent ductus arteriosus in ductal
      dependent pulmonary circulation.
AB  - OBJECTIVE: We sought to assess the outcome of transcatheter ductus arteriosus
      stenting in newborns with ductal-dependent pulmonary circulation. BACKGROUND:
      Better results of ductal stenting have been reported using stents with better
      scaffolding and ensuring stenting of the entire length of the ductus arteriosus.
      METHODS: Twenty-one patients with ductal-dependent pulmonary circulation were
      brought to the catheterization laboratory for ductal stenting. Five patients did
      not qualify because of a complex tortuous ductus arteriosus or branch pulmonary
      artery stenosis. Stent implantation was successful in 14 patients. The duct was
      accessed with a 0.014-inch guidewire. A low profile premounted coronary stent was
      implanted in the duct without using a long delivery sheath. Attempts were made to
      cover the entire length of the ductus arteriosus. RESULTS: The mean age of the
      patients at the time of stent implantation was 24 +/- 17.5 days. The mean body
      weight was 2.9 +/- 0.35 kg. The ductus was mildly tortuous in four, moderately
      tortuous in four, conical in four, and vertical in four patients. Ductal stenting
      was successful in 14 patients. The mean ductal diameter was 3.9 +/- 0.5 mm. The
      mean diameter and the length of the stent implanted were 3.9 +/- 0.72 and 15.4 +/
      3.16 mm, respectively. Mean fluoroscopy and procedure times were 22.16 +/- 12.5
      and 107.9 +/- 34.5 minutes, respectively. Out of the 14 successful stent
      implantations, the ductus arteriosus was not completely covered with the stent in
      five patients at the time of primary procedure, four of them required re-stenting
      for significant desaturation. One of these patients died despite successful re
      stenting. Another patient died due to aspiration pneumonia. Of the 12 survivors,
      five underwent Glenn shunt (two deaths related to pulmonary hypertension), two
      underwent biventricular repair, one patient was lost to follow-up, and the
      remaining four are doing well with a mean oxygen saturation of 85% at a mean
      follow-up of 13 +/- 6 months. CONCLUSION: Stenting of ductus arteriosus,
      including moderately tortuous ducts, is a safe palliation for patients with
      ductal-dependent pulmonary circulation. Incomplete stenting of the duct
      invariably results in ductal stenosis and compromised pulmonary flow.

PMID- 18715458
TI  - Persistent sinus venosus valve requiring surgery in children.
AB  - OBJECTIVE: To review our experience with cardiac surgery due to remnants of the
      sinus venosus valve. DESIGN: We performed a retrospective evaluation of patients
      records during the period from 1980 to 2007. RESULTS: Three patients underwent
      surgical removal of the redundancy of the right sinus venosus valve. CONCLUSION:
      Remnants of the embryologic sinus venosus valve may present by various entities.
      Cardiac surgery should be performed only in patients with continuing symptoms
      attributed to a persistent sinus venosus valve.

PMID- 18715459
TI  - Exercise capacity improves after transcatheter closure of the Fontan fenestration
      in children.
AB  - OBJECTIVES: This study evaluated the aerobic capacity, exercise capacity, and
      arterial oxygen saturation (O(2)Sat) in children before and after transcatheter
      Fontan fenestration closure. DESIGN: Observational study comparing exercise
      parameters and hemodynamics before and after transcatheter fenestration closure
      in Fontan patients. OUTCOME MEASURES: Working capacity, exercise duration, oxygen
      consumption (VO(2)), and arterial O(2)Sat were evaluated during aerobic exercise.
      RESULTS: Twenty patients (mean age 11.4 years) underwent standardized exercise
      testing before and after fenestration closure. Twelve patients underwent cycle
      ergometry testing (mean age 14.8 years) (group 1), and eight younger patients
      (mean age 6.4 years) underwent Bruce treadmill testing (group 2). The same
      exercise protocol was used in each patient before and after fenestration closure
      (interval between tests: 118 +/- 142 days). Immediately following fenestration
      closure at cardiac catheterization, cardiac index decreased (3.0 to 2.1
      L/minute/m(2)) and Fontan pressure increased (11 +/- 2 to 12 +/- 2 mm Hg) with an
      increased arterial saturation (92 to 96%) (P < .001). The total group
      demonstrated no significant change in pre- and postclosure maximal heart rates
      (164 +/- 21 and 169 +/- 19 bpm). Rest and exercise O(2)Sat increased (89 and 82
      to 95 and 92%) (P < .0001). Exercise duration increased (7.7 +/- 1.9 to 9.2 +/-
      2.4 minutes) (P < .0005). Maximal VO(2), indexed maximal VO(2), and total working
      capacity in kilopond-meters (kpm) increased (1.2 +/- 0.5, 27 +/- 7 and 2466 +/-
      1012 to 1.3 +/- 0.4 L/minute, 31 +/- 9 mL/kg/minute and 2869 +/- 1051 kpm,
      respectively) (P < .005). CONCLUSION: In children with a univentricular heart
      after Fontan palliation, transcatheter fenestration closure improves exercise
      arterial O(2)Sat and aerobic capacity despite a restricted resting cardiac output
      documented by catheterization immediately after the closure procedure.

PMID- 18715460
TI  - Protein-losing enteropathy after the Fontan operation: associations and
      predictors of clinical outcome.
AB  - OBJECTIVE: We sought to define what clinical parameters were related to the
      ultimate outcome in Fontan patients who had developed protein-losing enteropathy
      (PLE). BACKGROUND: PLE is a serious complication of the Fontan operation. Several
      preoperative and perioperative findings are associated with later PLE. However,
      there is limited information regarding postoperative abnormalities contributing
      to or influencing outcome in PLE. METHODS: We evaluated 44 consecutive Fontan
      patients with PLE. A matched control group of Fontan patients without PLE was
      used for comparison (matched-pair analyses). Kaplan-Meier and Cox proportional
      hazard methods were used for survival analyses. RESULTS: Median age was 18 years
      (range 4-48 years). Short-axis and apical fractional area change (Delta FA) were
      less in PLE patients than in controls (50 vs. 57% [P < .0001] and 49 vs. 54% [P =
      .01]). Five and 10-year actuarial survival rates for the PLE group were 49 +/- 9%
      and 30 +/- 11%. Deceleration time <120 milliseconds (hazard ratio [HR] = 9.2, P =
      .04), New York Heart Association classification III or IV (HR = 4.0, P = .01),
      and lower serum albumin (HR = 0.30, P = .04) were independent predictors of
      mortality in those with PLE. CONCLUSION: Mild reduction in Delta FA was the only
      late echocardiographic finding associated with development of PLE. However, short
      deceleration time, poor New York Heart Association (NYHA) class, and low serum
      albumin identify a group of patients at the greatest risk for death. Presence of
      these findings in a PLE patient should lead to aggressive management strategies
      and may warrant early consideration of transplantation.

PMID- 18715461
TI  - Lymphatic obstruction and protein-losing enteropathy in patients with congenital
      heart disease.
AB  - OBJECTIVE: Protein-losing enteropathy (PLE) is a known complication of surgical
      procedures for congenital heart disease. The pathogenesis and pathophysiology of
      PLE remain poorly understood. However, lymphatic insufficiency appears central to
      the disease process. We sought to investigate the role of lymphatic obstruction
      and central venous catheter-related central venous thrombosis in patients with
      congenital heart disease and PLE. DESIGN: A case-control study design was
      constructed consisting of patients with congenital heart disease and PLE and 2:1
      matched controls having undergone the same definitive surgical procedure.
      Obstruction to lymphatic return was considered present if the thoracic duct was
      ligated, or if there was complete central venous obstruction at the usual site of
      thoracic duct drainage. RESULTS: Obstruction to lymphatic return was identified
      in 4 of 16 cases (25%) and 1 of 32 controls (4%), P = .06. There was no
      association between PLE and central venous catheter use or duration, and no
      discriminating characteristics between cases and controls with respect to
      anatomy, pre-Fontan hemodynamic variables, operative or perioperative factors, or
      hemodynamic variables at the time of PLE diagnosis. Mortality for patients with
      PLE was 25% compared with 9% in controls (P = not significant). Long-term
      resolution of PLE was obtained in six patients (38%). CONCLUSION: There is a high
      prevalence of apparent lymphatic obstruction in patients with congenital heart
      disease and PLE, suggesting that physical lymphatic obstruction may play an
      important, and previously unrecognized role in the development of PLE in patients
      with complex congenital heart disease.

PMID- 18715462
TI  - Menstrual cycle and its disorders in women with congenital heart disease.
AB  - OBJECTIVES: To investigate the age at menarche, the prevalence of menstrual cycle
      (interval) disorders, and determinants in women with congenital heart disease
      (CHD). DESIGN: Using two CHD registries, 1802 (82%) of the 2196 women with CHD
      contacted (aged 18-58 years) provided written informed consent. After exclusion
      of patients with genetic disorders known to be associated with menstrual cycle
      disorders, 1593 eligible patients remained. Interviews by telephone and reviews
      of medical records were conducted. RESULTS: Overall, the age at menarche was
      slightly increased in women with CHD (13.3 vs. 13.1 years in the general
      population), mainly attributable to an increased prevalence of primary amenorrhea
      (n = 147; 9.2%). Other menstrual cycle disorders were documented: secondary
      amenorrhea (n = 181, 11.4%), polymenorrhea (n = 103, 6.5%), oligomenorrhea (n =
      90, 5.6%), and menorrhagia (n = 117, 6.5%). The occurrence of these disorders
      also depended on the presence of cyanotic heart disease, surgical status, the
      number of surgical interventions, and the severity of CHD. DISCUSSION: Menstrual
      cycle disturbances, in particular primary amenorrhea, were frequently observed in
      this population. Patients with complex (cyanotic) heart disease needing repeated
      surgical interventions prior to menarche are especially at risk.

PMID- 18715463
TI  - Atypical mycobacterial infection in sequestrated lung in an infant presenting
      with chronic pneumonitis and recurrent wheezing.
AB  - An infant was referred to us for persistent cough and recurrent wheezing. Chest X
      ray showed an abnormal shadow in the right lower lobe. A volumetric contrast
      enhanced computerized tomography (CT) scan of the chest revealed an abnormal
      blood vessel extending from the descending aorta to the right lower lobe and
      anomalous venous drainage from the right lower lobe into inferior vena cava.
      Angiography confirmed the CT scan findings. Pulmonary sequestration associated
      with scimitar syndrome was subsequently diagnosed. Patient underwent right lower
      lobectomy and right inferior pulmonary vein was anastomosed into the left atrium.
      Pathological examination after surgery revealed epitheloid granuloma in the
      sequestrated lung parenchyma and mycobacteria in the draining lymph nodes. This
      is a rare case of pulmonary sequestration associated with scimitar syndrome and
      complicated by mycobacterial infection.

PMID- 18715464
TI  - Imaging of extralobar pulmonary sequestration in a patient with tetralogy of
      Fallot with pulmonary atresia, ventricular septal defect and multiple aorto
      pulmonary collateral arteries with multidetector computed tomography.
AB  - Complex pulmonary vascular blood supply is common in patients with tetralogy of
      Fallot with pulmonary atresia, major systemic to pulmonary collateral arteries
      and hypoplastic or deficient central pulmonary arteries. An extralobar lung
      sequestration, which has not been described previously in these patients, was
      imaged in a 6-week-old infant with multidetector computed tomography with sub
      millimeter resolution. Arterial and venous vessels were analyzed using three
      dimensional vascular exploration tools and results were confirmed with cardiac
      catheterization.

PMID- 18715465
TI  - Giant cell aortitis and Noonan syndrome.
AB  - An 18-year-old girl with Noonan syndrome was diagnosed with progressive
      aneurysmal dilatation of the ascending aorta. Histopathological examination
      revealed giant cell aortitis. Connective tissue abnormalities leading to aortic
      root dilatation and the sinuses of Valsalva aneurysm have been reported in Noonan
      syndrome. This report is the first description of giant cell aortitis in Noonan
      syndrome and may provide a link between aortic aneurysm, and giant cell granuloma
      of bone in Noonan syndrome.

PMID- 18715466
TI  - Coronary recanalization due to presumed thrombosis following surgical ligation of
      a large right coronary artery to right ventricle fistula.
AB  - We report angiographic findings in an infant with congestive heart failure due to
      a large right coronary artery to right ventricular fistula who underwent surgical
      ligation. Repeat catheterization 2 years later unexpectedly showed extensive
      thrombosis of the right coronary artery with multiple recanalized channels
      supplying the right coronary distribution. Review of the literature showed that
      this may not be an uncommon finding.

PMID- 18715467
TI  - Argatroban anticoagulation for cardiac surgery with cardiopulmonary bypass in an
      infant with double outlet right ventricle and a history of heparin-induced
      thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of
      heparin therapy. Anticoagulation in pediatric patients with HIT is challenging as
      there are no approved heparin substitutes. We report the use of the anticoagulant
      argatroban for cardiac surgery with cardiopulmonary bypass in an infant with
      double outlet right ventricle and a history of HIT.

PMID- 18715468
TI  - Catheter-guided open ligation of a pulmonary artery to left atrium connection.
AB  - Congenital malformations causing mild cyanosis can be overlooked. A large
      intrapulmonary right pulmonary artery to left atrium connection was the unusual
      etiology of arterial oxygen desaturation and erythrocytosis in an asymptomatic 30
      year-old patient. The shunt was not possible to detect at echocardiography. It
      was closed via a median sternotomy without the aid of cardiopulmonary bypass. A
      novel technique was to use an angiographic catheter inserted through the wide
      shunt into the left atrium before the operation to securely identify it at the
      surgical dissection.

PMID- 18715470
TI  - Comparison of three research models of portal hypertension in mice: macroscopic,
      histological and portal pressure evaluation.
AB  - The characterization of mice models of portal hypertension (PHT) is lacking in
      the literature. Therefore, the aim of the present study was to make a
      histological approach during development of PHT in two models of cirrhosis with
      PHT compared with one model of isolated PHT. The model of isolated PHT was
      developed by partial portal vein ligation (PPVL). Two portal hypertensive
      cirrhotic mice models were developed either by common bile duct ligation (CBDL)
      or administration of carbon tetrachloride (CCl(4)) subcutaneously (twice weekly,
      1 ml/kg). These models represent, respectively, a secondary biliary cirrhosis and
      alcoholic cirrhosis. Mice were killed at several time points to evaluate liver
      changes by histological and ultrastructural methods. A correlation was made with
      portal pressure measurements. Histology revealed the absence of fibrosis or
      cirrhosis in PPVL mice. They developed an isolated portal hypertension. After
      CBDL induction, the mice developed the characteristics of cirrhosis after 6
      weeks, with simultaneous increase in portal pressures. Fifty percent of the mice
      had ascites at that time point. Sixteen weeks after administration of CCl(4), a
      micronodular cirrhotic aspect of the liver was seen associated with signs of
      portal hypertension. This is the first descriptive study of three widely used
      animal models in mice, allowing the study of pathophysiological changes in
      cirrhosis and portal hypertension. The PPVL in mice leads to a model of isolated
      portal hypertension. Secondary biliary cirrhosis developed after 6 weeks of
      common bile duct ligation in 50% of the mice that developed ascites. Subcutaneous
      injection of CCl(4) for 16 weeks induces cirrhosis and portal hypertension,
      without ascites. Moreover, the present study is the first description of a
      cirrhotic model in mice developed by subcutaneous injections of CCl(4). Well
      described mice models will facilitate use of knock-out or transgenic mice and
      lead to a better understanding of the underlying molecular pathways in the field
      of portal hypertension and cirrhosis.

PMID- 18715471
TI  - Malignant lesions in the ventral prostate of alloxan-induced diabetic rats.
AB  - The aim of this study was to evaluate the changes caused by chronic diabetes in
      the rat ventral prostate and to establish a correlation between diabetes and the
      development of prostatic lesions. Male rats received alloxan (42 mg/kg b.w.) to
      induce diabetes. Ninety days after diabetes diagnosis, animals were sacrificed
      and the ventral prostate was removed and prepared for general and
      immunohistochemical analyses. The total area showing different types of lesions
      was estimated. Diabetes led to a decrease in the body and prostatic weights, as
      well as in testosterone levels. The prostate morphology and stereology showed
      high variation in the diabetic group. Some animals had light changes; the great
      majority had an intense epithelial atrophy; and other rats showed premalignant
      and malignant lesions in the prostate. Such epithelial atrophy was, in some
      samples, combined with chronic inflammation, similar to proliferative
      inflammatory atrophy (PIA). The diabetic group also presented high incidence of
      prostatitis, adenocarcinoma and prostatic intra-epithelial neoplasia (PIN).
      Samples with adenocarcinoma had poorly differentiated acini with high levels of
      cellular proliferation and nuclear atypia. These lesions exhibited an invasive
      feature showing Bcl-2-positive cells and interruptions in the basement membrane.
      An association of PIA, PIN and adenocarcinoma was detected in one sample. Reduced
      androgen levels have a synergic effect to insulin dysfunction promoting negative
      effects in the rat prostate. Diabetic individuals had a high incidence of
      prostatitis, and this inflammation could stimulate the incidence of other forms
      of prostatic pathology.

PMID- 18715472
TI  - Effects of early postnatal hyperglycaemia on renal cortex maturity, endothelial
      nitric oxide synthase expression and nephron deficit in mice.
AB  - The influence of hyperglycaemia on nephrogenesis on Swiss mice pups treated with
      streptozotocin (STZ) (40 mg/kg, i.p.) was studied after birth, at 7 and 21 days.
      Kidneys were prepared for light microscopy, immunohistochemistry and stereology.
      In 7-day-old pups, both immature and mature glomeruli were evaluated separately.
      Proliferating cell nuclear antigen (PCNA) and endothelial nitric oxide synthase
      (eNOS) immunostaining were performed and quantified. At age 7 days, the immature
      to-mature glomeruli ratio (IMGR) was significantly higher in the STZ group than
      in the control group. There was no difference in the number of glomeruli between
      the STZ and control groups; however, the number of glomeruli increased by more
      than 20% in the control group until 21 days of age, but not in the STZ group. STZ
      pups showed numerous PCNA-positive nuclei mainly in tubular cells, but not
      control pups. At 21 days, eNOS expression in the outer layer of glomerular
      endothelial nuclei was strong in control pups, but weaker in STZ pups. Treatment
      with STZ during the early neonatal period disturbs the normal nephrogenesis
      occurring at this stage of the rodent's life and causes retardation in renal
      cortical maturity, as indicated by the increase in both PCNA expression and IMGR,
      and reduction in eNOS expression.

PMID- 18715473
TI  - Role of hyperglycaemia in the pathogenesis of hypotension observed in type-1
      diabetic rats.
AB  - The role of hyperglycaemia in the pathogenesis of hypotension in diabetic
      disorders was investigated using the changes in cardiac M(2)-muscarinic receptor
      (M(2)-mAChR) gene expression in type-1-like diabetic rats and cultured
      cardiomyocytes. Blood pressure was markedly decreased in diabetic rats following
      the intravenous injection of streptozotocin (STZ) for 8 weeks. Also, the
      baroreflex sensitivity (Delta HR/Delta BP), as measured by the changes in heart
      rate (Delta HR) and mean blood pressure (Delta BP) 1 min after the intravenous
      injection of phenylephrine (10 microg/kg), was significantly increased.
      Arecaidine propargyl ester (APE), a M(2)-mAChR agonist produced a marked
      reduction in heart rate in these diabetic rats. Normalization of plasma glucose
      in diabetic rats using insulin (0.5 IU) or phlorizin (1 mg/kg) injection
      attenuated the blood pressure reduction and reversed the mRNA and protein levels
      of cardiac M(2)-mAChR. A high concentration of glucose (20 mmol/l) directly
      influenced the increase in gene expression of M(2)-mAChR in the H9c2 cardiac cell
      line. Hyperglycaemia induced an increase in cardiac M(2)-mAChR gene expression,
      suggesting a role in the pathogenesis of hypotension in diabetic disorders.

PMID- 18715475
TI  - Understanding medical professionalism: a plea for an inclusive and integrated
      approach.

PMID- 18715476
TI  - The theory of planned behaviour in medical education: a model for integrating
      professionalism training.
AB  - CONTEXT: Teaching and evaluating professionalism remain important issues in
      medical education. However, two factors hinder attempts to integrate curricular
      elements addressing professionalism into medical school training: there is no
      common definition of medical professionalism used across medical education, and
      there is no commonly accepted theoretical model upon which to integrate
      professionalism into the curriculum. OBJECTIVES: This paper proposes a definition
      of professionalism, examines this definition in the context of some of the
      previous definitions of professionalism and connects this definition to the
      attitudinal roots of professionalism. The problems described above bring
      uncertainty about the best content and methods with which to teach
      professionalism in medical education. Although various aspects of professionalism
      have been incorporated into medical school curricula, content, teaching and
      evaluation remain controversial. We suggest that intervening variables, which may
      augment or interfere with medical students' implementation of professionalism
      knowledge, skills and, therefore, attitudes, may go unaddressed. DISCUSSION: We
      offer a model based on the theory of planned behaviour (TPB), which describes the
      relationships of attitudes, social norms and perceived behavioural control with
      behaviour. It has been used to predict a wide range of behaviours, including
      doctor professional behaviours. Therefore, we propose an educational model that
      expands the TPB as an organisational framework that can integrate professionalism
      training into medical education. We conclude with a discussion about the
      implications of using this model to transform medical school curricula to develop
      positive professionalism attitudes, alter the professionalism social norms of the
      medical school and increase students' perceived control over their behaviours.

PMID- 18715478
TI  - Holistic presentation of the undergraduate medical curriculum.

PMID- 18715477
TI  - Is it me or is it them? Factors that influence the passing of underperforming
      students.
AB  - CONTEXT: Research has found that clinical assessments do not always accurately
      reflect medical student performance. Barriers to failing underperformance in
      students have been identified in other vocational settings. Is 'failure to fail'
      an issue for medical educators in the UK, and, if so, what are its determinants?
      METHODS: We carried out a qualitative focus group study exploring the views of
      medical educators (general practitioners, hospital doctors and non-clinical
      tutors) from two different UK medical schools. To make sense of a potential
      multitude of factors impacting on failure to fail, we selected the integrative
      model of behavioural prediction to underpin our data collection and analysis.
      RESULTS: Ten focus groups were carried out with 70 participants. Using both
      theory and data-driven framework analysis, we identified six main themes relevant
      to the integrative model of behavioural prediction. These are: tutor attitudes
      towards an individual student; tutor attitudes towards failing a student;
      normative beliefs and motivation to comply; efficacy beliefs (self-efficacy);
      skills and knowledge, and environmental constraints. DISCUSSION: Many different
      factors impact on medical educators' failure to report underperformance in
      students. There are conflicts between these factors and the need to report
      competence accurately (i.e. duty to protect the public). Although some of the
      barriers identified are similar to those found in previous studies, using a
      theory-based approach added value in that it facilitated a richer exploration of
      failure to fail. Insights offered in this study will be used to plan a
      questionnaire study and subsequent intervention to support medical educators in
      accurately reporting underperformance in students.

PMID- 18715479
TI  - On the limits of systematicity.

PMID- 18715480
TI  - 'To call or not to call': making informed self-assessment.

PMID- 18715481
TI  - Apprenticeship learning models in residents: are they transferable to medical
      students?

PMID- 18715482
TI  - Meta-analysis of quasi-experimental research: are systematic narrative reviews
      indicated?
AB  - CONTEXT: Meta-analyses are commonly performed on quasi-experimental studies in
      medical education and other applied field settings, with little or no apparent
      concern for biases and confounds present in the studies synthesised. The implicit
      assumption is that the biases and confounds are randomly distributed across the
      studies and are averaged or cancelled out by the synthesis. OBJECTIVES: We set
      out to consider the possibility that the results and conclusions of meta-analyses
      in medical education are subject to biases and confounds and to illustrate this
      possibility with a re-examination of the studies synthesised in an important,
      recently published meta-analysis of problem-based learning. METHODS: We carefully
      re-examined the studies in the meta-analysis. Our aims were to identify obvious
      biases and confounds that provided plausible alternative explanations of each
      study's results and to determine whether these threats to validity were
      considered and convincingly ruled out as plausible rival hypotheses. RESULTS: Ten
      of the 11 studies in the meta-analysis used quasi-experimental designs; all 10
      were subject to constant biases and confounds that favoured the intervention
      condition. Threats to validity were not ruled out in the individual studies, nor
      in the meta-analysis itself. CONCLUSIONS: Our re-examination of the results and
      conclusions of the meta-analysis illustrates our concerns about the validity of
      meta-analyses based primarily on quasi-experimental studies. Our tentative
      conclusion is that the field of medical education might be better served in most
      instances by systematic narrative reviews that describe and critically evaluate
      individual studies and their results in light of threats to their validity.

PMID- 18715483
TI  - Expectation and experience: dissonances between novice and expert perceptions in
      medical education research.
AB  - CONTEXT: There is both qualitative and quantitative variation in the research
      methods training provided for Masters and doctoral students on medical education
      programmes across the UK. Unlike other higher-degree programmes, there are no
      requirements for higher-degree medical education students to have studied the
      subject at degree level or for their supervisors to have training in social
      science research methods. This study explores the ways in which a panel of
      experts responded to novices' presentations of their research in progress.
      METHODS: This qualitative, case-based study of a 1-day education research
      consortium generated data in two phases. The author collected detailed field
      notes as a non-participant observer and subsequently analysed the data they
      contained. A second set of data was generated from written reflexive accounts of
      the day e-mailed to the author by all participants 1 month after the event and
      was subsequently analysed. RESULTS: Thematic coding revealed wide degrees of
      variance between the research experiences and abilities of the novices and the
      expectations of the experts. These levels of dissonance are ascribed to the
      limited amounts of research training undertaken by students and the variable
      guidance provided by research supervisors, some of whom were themselves novices
      in this area. CONCLUSIONS: If medical education research is to thrive, it
      requires a properly developed infrastructure with training and support for
      research supervisors and students alike. Communities of practice need to be
      fostered to enable researchers to collaborate and disseminate good practice. This
      will ensure that medical education research practitioners can produce
      theoretically sound, rigorously designed and executed studies that can contribute
      to the evidence base for medical education.

PMID- 18715484
TI  - 'I don't have time': issues of fragmentation, prioritisation and motivation for
      education scholarship among medical faculty.
AB  - OBJECTIVES: Although lack of time has been frequently cited as a barrier to
      scholarship, there has been little inquiry into what specific factors medical
      faculty staff perceive as contributing to this dilemma. The purpose of the
      present study was to explore, in greater detail, lack of time as a barrier for
      faculty interested in pursuing education scholarship. METHODS: In 2004, as part
      of a cross-sectional, mixed-methods needs assessment, 73 (67.6%) medical faculty
      completed a questionnaire probing areas related to education scholarship.
      Additionally, one year later, 16 respondents (60% of those invited) each
      participated in one of three focus groups. RESULTS: Despite their interest and
      regardless of their background training in education, faculty were able, on
      average, to devote only negligible amounts of time to education scholarship. The
      most commonly reported barrier to these pursuits was lack of protected time.
      Further analysis revealed that the time-related factor appeared to involve three
      themes: fragmentation (where opportunities to work on education projects are
      sporadic); prioritisation (where work responsibilities including after-hours work
      and administrative workload complete for time, and where there is difficulty in
      securing financially remunerated time), and motivation (where the degree of
      recognition and support for education work by both the department and colleagues
      is limited). CONCLUSIONS: With respect to education scholarship, the dilemma
      caused by lack of time involves a complex, multi-faceted set of issues which
      extends beyond the number of hours available in a day. Personal interest and
      having background training in education do not appear to be sufficient to
      encourage involvement. Multiple institutional support mechanisms are necessary.

PMID- 18715485
TI  - CanMEDS evaluation in Canadian postgraduate training programmes: tools used and
      programme director satisfaction.
AB  - CONTEXT: The Royal College of Physicians and Surgeons of Canada (RCPSC) CanMEDS
      framework is being incorporated into specialty education worldwide. However, the
      literature on how to evaluate trainees in the CanMEDS competencies remains
      sparse. OBJECTIVES: The goals of this study were to examine the assessment tools
      used and programme directors' perceptions of how well they evaluate performance
      of the CanMEDS roles in Canadian postgraduate training programmes. METHODS: We
      conducted a web-based survey of programme directors of RCPSC-accredited training
      programmes. The survey consisted of two questions. Question 1 was designed to
      establish which assessment tools were used to assess each of the CanMEDS roles.
      Question 2 was intended to assess programme directors' perceived satisfaction
      with CanMEDS evaluation in their programmes. RESULTS: A total of 149 of the
      eligible 280 programme directors participated in the survey. Programme directors
      used a variety of assessment tools to evaluate trainees in CanMEDS competencies.
      Programmes used more tools to evaluate the Medical Expert (mean = 4.03, standard
      deviation [SD] = 1.59) and Communicator (mean = 2.36, SD = 1.02) roles. Programme
      directors used the fewest tools for the Collaborator (mean = 1.75, SD = 1.10) and
      Manager (mean = 1.75, SD = 1.18) roles. More than 92% of the programmes used in
      training evaluation reports to evaluate all the CanMEDS roles. Programme
      directors were satisfied with their evaluation of the Medical Expert role, but
      less so with assessment of the other CanMEDS competencies. CONCLUSIONS: This
      study demonstrates that Canadian postgraduate training programmes use a variety
      of assessment tools to evaluate the CanMEDS competencies. Programme directors are
      neutral or concerned about how the CanMEDS roles other than that of Medical
      Expert are evaluated in their programmes. Further efforts are required to
      establish best practice in CanMEDS evaluation.

PMID- 18715486
TI  - Reliability of the long case.
AB  - OBJECTIVES: The use of long cases for summative assessment of clinical competence
      is limited by concerns about unreliability. This study aims to explore the
      reliability of long cases and how reliability is affected by supplementation with
      short cases. METHODS: We performed a statistical analysis of examinations held by
      the Royal Australasian College of Physicians in 2005 and 2006 to determine
      overall reliability and sources of variance in reliability according to candidate
      ability, case difficulty and inter-examiner differences. RESULTS: Scores for 546
      long cases in 2005 and 773 long cases in 2006 were analysed. In 2006, 38% of the
      total variation in long case data was explained by variation in candidate
      ability, with other significant contributors to variance being candidate x case
      and candidate x examiner interactions. Similar figures were found for the 2005
      examinations. A short case is less reliable than a long case, but when examiner
      time is taken into account, three short cases are as reliable as one long case.
      Any combination of short and long cases would require 4-5 hours of testing time
      in order to achieve dependability > 0.7. CONCLUSIONS: Long cases can be optimised
      for reliability but time limits their use as the sole tool in a high-stakes
      examination. Further examiner training, better case selection, or greater use of
      short cases would have minimal impact on reliability. Reliability can be improved
      by either increasing examination time or including additional methods of
      summative assessment, such as might be provided by workplace assessment.

PMID- 18715487
TI  - Use of a structured interview to assess portfolio-based learning.
AB  - CONTEXT: Portfolio-based learning is a popular educational tool usually examined
      by document review which is sometimes accompanied by an oral examination. This
      labour-intensive assessment method prohibits its use in the resource-constrained
      settings typical of developing countries. OBJECTIVES: We aimed to determine the
      feasibility and internal consistency of a portfolio-based structured interview
      and its impact on student learning behaviour. METHODS: Year 4 medical students (n
      = 181) recorded 25 patient encounters during a 14-week medical clerkship.
      Portfolios were examined in a 30-minute, single-examiner interview in which four
      randomly selected cases were discussed. Six standard questions were used to guide
      examiners in determining the ability of candidates to interpret and synthesise
      clinical data gathered during patient encounters. Examiners were trained to score
      responses using a global rating scale. Pearson's correlation co-efficient,
      Cronbach's alpha coefficient and the standard error of measurement (SEM) of the
      assessment tool were determined. The number of students completing more than the
      required number of portfolio entries was also recorded. RESULTS: The mean (+/-
      standard deviation [SD], 95% confidence interval [CI]) interview score was 67.5%
      (SD +/- 10.5, 95% CI 66.0-69.1). The correlation coefficients for the interview
      compared with other component examinations of the assessment process were:
      multiple-choice question (MCQ) examination 0.42; clinical case-based examination
      0.37; in-course global rating 0.08, and overall final score 0.54. Cronbach's
      alpha coefficient was 0.88 and the SEM was 3.6. Of 181 students, 45.3% completed
      more than 25 portfolio entries. CONCLUSIONS: Portfolio assessment using a 30
      minute structured interview is a feasible, internally consistent assessment
      method that requires less examination time per candidate relative to methods
      described in published work and which may encourage desirable student learning
      behaviour.

PMID- 18715488
TI  - Teaching doctors how to diagnose paroxysmal events: a comparison of two
      educational methods.
AB  - OBJECTIVES: Two educational methods, facilitated case discussion and a
      computerised tutorial, were compared for teaching about childhood epilepsy. We
      used a comprehensive and clinically relevant assessment method to evaluate the
      hypothesis that a computerised tutorial more effectively increases knowledge
      acquisition than a facilitated case discussion. METHODS: Paediatric trainees (n =
      66) were arbitrarily allocated to facilitated case discussion or computerised
      tutorial. The analysis of paroxysmal events was taught by the same teacher, using
      a standardised protocol and principles of active learning. Outcome measures
      included knowledge acquisition, clinical confidence and usefulness pre- and post
      teaching, and at 3 months follow-up. RESULTS: Computerised tutorial participants
      scored significantly higher on knowledge acquisition post-teaching. There was
      gain in clinical confidence in both modalities post-teaching which did not differ
      between the groups. Confidence and knowledge were not related post-teaching. Both
      groups found the teaching relevant to clinical practice. However, facilitated
      case discussion participants rated the session as more enjoyable, and more useful
      in reinforcing and acquiring knowledge, and felt more motivated for further
      learning. At 3 months follow-up, participants in both modalities showed
      significant increases in knowledge acquisition, with no difference between
      modalities. CONCLUSIONS: The computerised tutorial more effectively imparted
      knowledge immediately post-teaching. However, facilitated case discussion is the
      preferred modality in terms of participant enjoyment and perceived usefulness.

PMID- 18715489
TI  - Development of a framework of medical undergraduate teaching activities.
AB  - CONTEXT: The need for a comprehensive framework of teaching activities in
      undergraduate medical education was identified by colleagues involved in teacher
      training at the University of Edinburgh, UK and Karolinska Institutet, Sweden.
      Such a framework could be used to develop training programmes for medical
      teachers, to help experienced teachers to reflect upon and communicate with
      others about their practice, and as a focus for further research on medical
      teaching. METHODS: A provisional framework of medical teaching activities and a
      model illustrating how these activities are situated within the wider context of
      learning and teaching were developed iteratively using the literature and pilot
      studies. The provisional framework and model were then methodically tested using
      journal analysis, brainstorming sessions and focus group sessions with medical
      teachers and teacher trainers in both institutions. Data gathered from this
      research were analysed and used to further develop the framework and model.
      RESULTS: Many of the provisional teaching activities in the framework were
      further developed in response to the research data and some new activities were
      added. Teaching activities seemed to cluster into three domains: 'Facilitating',
      'Managing', and 'Learning and Community Building'. Specific tasks were identified
      relating to planning, administering, resourcing, implementing and evaluating each
      teaching activity. Participants found the model of learning and teaching helpful
      and felt it adequately represented the place of teaching activities within the
      wider context of undergraduate medical education. The framework and model are now
      being used by the authors in faculty development, undergraduate teaching and
      further research.

PMID- 18715490
TI  - Understanding paediatric resident-continuity preceptor relationships through the
      lens of apprenticeship learning.
AB  - CONTEXT: Apprenticeship learning is common in medical education, but is often
      situated in theoretical frameworks which highlight its cognitive but not its
      social dimension. METHODS: We conducted an ethnographic case study of paediatric
      residents' learning relationships with their preceptors in a community-based
      paediatric continuity site. It included 5 months (100 hours) of direct
      observation, and semi-structured interviews with 10 residents (before and after
      observation) and 10 primary care paediatricians who served as their continuity
      preceptors (after observation). Interview transcripts and notes from observations
      were inductively coded and analysed for major themes. RESULTS: Our observations
      and reports of resident learning trajectories fit well with the concept of
      legitimate peripheral participation. Residents learned the everyday practice of
      primary care as they worked alongside experienced paediatricians in the
      continuity clinic. Although the direction of learning was towards central
      participation in patient care, residents learned during transient shifts to the
      periphery of practice. As a function of residents' increased participation,
      preceptors moved into more supportive roles. Residents were not only learners; at
      times they were teachers who facilitated preceptors' learning. CONCLUSIONS:
      Legitimate peripheral participation is a concept that helps to explain
      apprenticeship as a dynamic social relationship which shapes, and is shaped by,
      learning that takes place in clinical practice. Other concepts shed light on the
      bidirectional nature of apprenticeship learning.

PMID- 18715492
TI  - Different Internet service providers produce different search results.

PMID- 18715491
TI  - To call or not to call: a judgement of risk by pre-registration house officers.
AB  - OBJECTIVES: This study set out to answer the following questions. What influences
      a junior doctor's response to a judgement call within a clinical setting? What,
      if any, are the relationships between these influences? METHODS: This paper
      describes an interpretivist study based on a grounded theory approach to data
      analysis. This involved a phased approach to data collection using semi
      structured interviews. Analysis was facilitated by observations and group
      presentations. Participants were doctors in their first year of postgraduate
      practice who were purposively selected from a range of hospitals in the Northern
      Deanery. RESULTS: The data demonstrated a number of influences on whether junior
      doctors chose to seek senior assistance. These included the upholding and
      balancing of tenets that were necessary for ensuring safe practice, and
      estimating the chance and severity of potential negative consequences to
      patients, themselves and their teams. In order to make these judgements, junior
      doctors drew on different forms of knowledge, especially knowledge gained from
      previous clinical experiences. In judging whether or not to contact a senior, pre
      registration house officers (PRHOs) were practising essential clinical
      attributes, that of independent yet co-operative and discerning practitioners who
      are able to balance multiple considerations while ensuring patient care.
      CONCLUSIONS: This particular judgement of risk, as it was described by those
      interviewed, was a dynamic process exemplified by the need to create
      counterbalances between multiple consequences. As a result, no prescriptive
      action could have allowed PRHOs to deal with the numerous configurations they
      faced and took into account.

PMID- 18715493
TI  - Anti-inflammatory effects of beta3-adrenoceptors: the burgeoning field of
      neurogastroimmunology.

PMID- 18715494
TI  - Novel pharmacology: asimadoline, a kappa-opioid agonist, and visceral sensation.
AB  - Asimadoline is a potent kappa-opioid receptor agonist with a diaryl acetamide
      structure. It has high affinity for the kappa receptor, with IC(50) of 5.6 nmol
      L(-1) (guinea pig) and 1.2 nmol L(-1) (human recombinant), and high selectively
      with kappa : micro : delta binding ratios of 1 : 501 : 498 in human recombinant
      receptors. It acts as a complete agonist in in vitro assay. Asimadoline reduced
      sensation in response to colonic distension at subnoxious pressures in healthy
      volunteers and in irritable bowel syndrome (IBS) patients without alteration of
      colonic compliance. Asimadoline reduced satiation and enhanced the postprandial
      gastric volume (in female volunteers). However, there were no significant effects
      on gastrointestinal transit, colonic compliance, fasting or postprandial colonic
      tone. In a clinical trial in 40 patients with functional dyspepsia (Rome II),
      asimadoline did not significantly alter satiation or symptoms over 8 weeks.
      However, asimadoline, 0.5 mg, significantly decreased satiation in patients with
      higher postprandial fullness scores, and daily postprandial fullness severity
      (over 8 weeks); the asimadoline 1.0 mg group was borderline significant. In a
      clinical trial in patients with IBS, average pain 2 h post-on-demand treatment
      with asimadoline was not significantly reduced. Post hoc analyses suggest that
      asimadoline was effective in mixed IBS. In a 12-week study in 596 patients,
      chronic treatment with 0.5 mg and 1.0 mg asimadoline was associated with adequate
      relief of pain and discomfort, improvement in pain score and number of pain-free
      days in patients with IBS-D. The 1.0 mg dose was also efficacious in IBS
      alternating. There were also weeks with significant reduction in bowel frequency
      and urgency. Asimadoline has been well tolerated in human trials to date.

PMID- 18715495
TI  - The Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH) can measure
      the impairment, activity limitations and participation restriction constructs
      from the International Classification of Functioning, Disability and Health
      (ICF).
AB  - BACKGROUND: The International Classification of Functioning, Disability and
      Health (ICF) model of the consequences of disease identifies three health
      outcomes, impairment, activity limitations and participation restrictions.
      However, few orthopaedic health outcome measures were developed with reference to
      the ICF. This study examined the ability of a valid and frequently used measure
      of upper limb function, namely the Disabilities of the Arm, Shoulder and Hand
      Questionnaire (DASH), to operationalize the ICF. METHODS: Twenty-four judges used
      the method of Discriminant Content Validation to allocate the 38 items of the
      DASH to the theoretical definition of one or more ICF outcome. One-sample t-tests
      classified each item as measuring, impairment, activity limitations,
      participation restrictions, or a combination thereof. RESULTS: The DASH contains
      items able to measure each of the three ICF outcomes with discriminant validity.
      The DASH contains five pure impairment items, 19 pure activity limitations items
      and three participation restriction items. In addition, seven items measured both
      activity limitations and participation restrictions. CONCLUSION: The DASH can
      measure the three health outcomes identified by the ICF. Consequently the DASH
      could be used to examine the impact of trauma and subsequent interventions on
      each health outcome in the absence of measurement confound.

PMID- 18715497
TI  - Implementation of a model for identifying Essentially Derived Varieties in
      vegetatively propagated Calluna vulgaris varieties.
AB  - BACKGROUND: Variety protection is of high relevance for the horticultural
      community and juridical cases have become more frequent in a globalized economy
      due to essential derivation of varieties. This applies equally to Calluna
      vulgaris, a vegetatively propagated species from the Ericaceae family that
      belongs to the top-selling pot plants in Europe. We therefore analyzed the
      genetic diversity of 74 selected varieties and genotypes of C. vulgaris and 3 of
      Erica spp. by means of RAPD and iSSR fingerprinting using 168 mono- and
      polymorphisms. The same data set was utilized to generate a system to reliably
      identify Essentially Derived Varieties (EDVs) in C. vulgaris, which was adapted
      from a method suggested for lettuce and barley. This system was developed,
      validated and used for selected tests of interest in C. vulgaris. RESULTS: As
      expected following personal communications with breeders, a very small genetic
      diversity became evident within C. vulgaris when investigated using our molecular
      methods. Thus, a dendrogram-based assay to detect Essentially Derived Varieties
      in this species is not suitable, although varieties are propagated vegetatively.
      In contrast, the system applied in lettuce, which itself applies pairwise
      comparisons using appropriate reference sets, proved functional with this
      species. CONCLUSION: The narrow gene pool detected in C. vulgaris may be the
      genetic basis for juridical conflicts between breeders. We successfully tested a
      methodology for identification of Essentially Derived Varieties in highly
      identical C. vulgaris genotypes and recommend this for future proof of essential
      derivation in C. vulgaris and other vegetatively propagated crops.

PMID- 18715496
TI  - How useful are systematic reviews for informing palliative care practice? Survey
      of 25 Cochrane systematic reviews.
AB  - BACKGROUND: In contemporary medical research, randomised controlled trials are
      seen as the gold standard for establishing treatment effects where it is ethical
      and practical to conduct them. In palliative care such trials are often
      impractical, unethical, or extremely difficult, with multiple methodological
      problems. We review the utility of Cochrane reviews in informing palliative care
      practice. METHODS: Published reviews in palliative care registered with the
      Cochrane Pain, Palliative and Supportive Care Group as of December 2007 were
      obtained from the Cochrane Database of Systematic Reviews, issue 1, 2008. We
      reviewed the quality and quantity of primary studies available for each review,
      assessed the quality of the review process, and judged the strength of the
      evidence presented. There was no prior intention to perform any statistical
      analyses. RESULTS: 25 published systematic reviews were identified. Numbers of
      included trials ranged from none to 54. Within each review, included trials were
      heterogeneous with respect to patients, interventions, and outcomes, and the
      number of patients contributing to any single analysis was generally much lower
      than the total included in the review. A variety of tools were used to assess
      trial quality; seven reviews did not use this information to exclude low quality
      studies, weight analyses, or perform sensitivity analysis for effect of low
      quality. Authors indicated that there were frequently major problems with the
      primary studies, individually or in aggregate. Our judgment was that the
      reviewing process was generally good in these reviews, and that conclusions were
      limited by the number, size, quality and validity of the primary studies.We
      judged the evidence about 23 of the 25 interventions to be weak. Two reviews had
      stronger evidence, but with limitations due to methodological heterogeneity or
      definition of outcomes. No review provided strong evidence of no effect.
      CONCLUSION: Cochrane reviews in palliative care are well performed, but fail to
      provide good evidence for clinical practice because the primary studies are few
      in number, small, clinically heterogeneous, and of poor quality and external
      validity. They are useful in highlighting the weakness of the evidence base and
      problems in performing trials in palliative care.

PMID- 18715498
TI  - Transhiatal esophagectomy in a high volume institution.
AB  - BACKGROUND: The optimal operative approach for carcinoma at the lower esophagus
      and esophagogastric junction remains controversial. The aim of this study was to
      assess a single unit experience of transhiatal esophagectomy in an era when the
      use of systemic oncological therapies has increased dramatically. STUDY DESIGN:
      Between January 2000 and November 2006, 215 consecutive patients (182 males, 33
      females, median age = 65 years) underwent transhiatal esophagectomy; invasive
      malignancy was detected preoperatively in 188 patients. 90 patients (42%)
      received neoadjuvant chemotherapy. Prospective data was obtained for these
      patients and cross-referenced with cancer registry survival data. RESULTS: There
      were 2 in-hospital deaths (0.9%). Major complications included: respiratory
      complications in 65 patients (30%), cardiovascular complications in 31 patients
      (14%) and clinically apparent anastomotic leak in 12 patients (6%). Median length
      of hospital stay was 14 days. The radicality of resection was inversely related
      to T stage: an R0 resection was achieved in 98-100% of T0/1 tumors and only 14%
      of T4 tumors. With a median follow up of 26 months, one and five year survival
      rates were estimated at 81% and 48% respectively. CONCLUSION: Transhiatal
      esophagectomy is an effective operative approach for tumors of the infracarinal
      esophagus and the esophagogastric junction. It is associated with low mortality
      and morbidity and a five survival rate of nearly 50% when combined with
      neoadjuvant chemotherapy.

PMID- 18715499
TI  - Identification of low penetrance alleles for lung cancer: the GEnetic Lung CAncer
      Predisposition Study (GELCAPS).
AB  - BACKGROUND: Part of the inherited risk to lung cancer is likely to include
      common, low risk alleles. The identification of this class of susceptibility is
      contingent on association-based analyses. We established GEnetic Lung CAncer
      Predisposition Study (GELCAPS) to collect DNA and clinico-pathological data from
      a large series of cases and a series of spouse/partner controls, thereby
      generating a key resource for the identification of low risk alleles. METHODS:
      GELCAPS was one of the first genetic epidemiological trials in the UK to be
      adopted by the National Cancer Research Network (NCRN) onto its portfolio with
      the participation of over 100 oncology departments specialising in the management
      of lung cancer. RESULTS: Samples from over 5,000 independent lung cancer cases
      and 2,000 controls have so far been assembled through GELCAPS. CONCLUSION:
      GELCAPS represents one of the largest datasets of its type in the world capable
      of informing on the contribution of low penetrance alleles to the development of
      lung cancer and the influence of genetic variation on outcome. In addition our
      experience in developing the GELCAPS serves to illustrate how large DNA biobanks
      for genetic analyses can be rapidly generated within the UK using the NCRN.

PMID- 18715500
TI  - The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes
      their activity in the anterior neural plate.
AB  - BACKGROUND: Secreted frizzled related proteins (SFRPs) are multifunctional
      modulators of Wnt and BMP (Bone Morphogenetic Protein) signalling necessary for
      the development of most organs and the homeostasis of different adult tissues.
      SFRPs fold in two independent domains: the cysteine rich domain (SfrpCRD) related
      to the extracellular portion of Frizzled (Fz, Wnt receptors) and the Netrin
      module (SfrpNTR) defined by homologies with molecules such as Netrin-1,
      inhibitors of metalloproteinases and complement proteins. Due to its structural
      relationship with Fz, it is believed that SfrpCRD interferes with Wnt signalling
      by binding and sequestering the ligand. In contrast, the functional relevance of
      the SfrpNTR has been barely addressed. RESULTS: Here, we combine biochemical
      studies, mutational analysis and functional assays in cell culture and medaka
      fish embryos to show that the Sfrp1NTR mimics the function of the entire
      molecule, binds to Wnt8 and antagonizes Wnt canonical signalling. This activity
      requires intact tertiary structure and is shared by the distantly related Netrin
      1NTR. In contrast, the Sfrp1CRD cannot mirror the function of the entire molecule
      in vivo but interacts with Fz receptors and antagonizes Wnt8-mediated beta
      catenin transcriptional activity. CONCLUSION: On the basis of these results, we
      propose that SFRP modulation of Wnt signalling may involve multiple and
      differential interactions among Wnt, Fz and SFRPs.

PMID- 18715501
TI  - Critical role for BIM in T cell receptor restimulation-induced death.
AB  - BACKGROUND: Upon repeated or chronic antigen stimulation, activated T cells
      undergo a T cell receptor (TCR)-triggered propriocidal cell death important for
      governing the intensity of immune responses. This is thought to be chiefly
      mediated by an extrinsic signal through the Fas-FasL pathway. However, we
      observed that TCR restimulation still potently induced apoptosis when this
      interaction was blocked, or genetically impaired in T cells derived from
      autoimmune lymphoproliferative syndrome (ALPS) patients, prompting us to examine
      Fas-independent, intrinsic signals. RESULTS: Upon TCR restimulation, we
      specifically noted a marked increase in the expression of BIM, a pro-apoptotic
      Bcl-2 family protein known to mediate lymphocyte apoptosis induced by cytokine
      withdrawal. In fact, T cells from an ALPS type IV patient in which BIM expression
      is suppressed were more resistant to restimulation-induced death. Strikingly,
      knockdown of BIM expression rescued normal T cells from TCR-induced death to as
      great an extent as Fas disruption. CONCLUSION: Our data implicates BIM as a
      critical mediator of apoptosis induced by restimulation as well as growth
      cytokine withdrawal. These findings suggest an important role for BIM in
      eliminating activated T cells even when IL-2 is abundant, working in conjunction
      with Fas to eliminate chronically stimulated T cells and maintain immune
      homeostasis. REVIEWERS: This article was reviewed by Dr. Wendy Davidson
      (nominated by Dr. David Scott), Dr. Mark Williams (nominated by Dr. Neil
      Greenspan), and Dr. Laurence C. Eisenlohr.

PMID- 18715502
TI  - Patient characteristics associated with differences in patients' evaluation of
      their general practitioner.
AB  - BACKGROUND: Knowledge of the extent to which patient characteristics are
      systematically associated with variation in patient evaluations will enable us to
      adjust for differences between practice populations and thereby compare GPs.
      Whether this is appropriate depends on the purpose for which the patient
      evaluation was conducted. Associations between evaluations and patient
      characteristics may reflect gaps in the quality of care or may be due to inherent
      characteristics of the patients. This study aimed to determine such associations
      in a setting with a comprehensive list system and gate-keeping. METHODS: A
      nationwide Danish patient evaluation survey among voluntarily participating GPs
      using the EUROPEP questionnaire, which produced 28,260 patient evaluations
      (response rate 77.3%) of 365 GPs. In our analyses we compared the prevalence of
      positive evaluations in groups of patients. RESULTS: We found a positive GP
      assessment to be strongly associated with increasing patient age and increasing
      frequency of attendance. Patients reporting a chronic condition were more
      positive, whereas a low self-rated health was strongly associated with less
      positive scores also after adjustment. The association between patient gender and
      assessment was weak and inconsistent and depended on the focus. We found no
      association either with the patients' educational level or with the duration of
      listing with the GP even after adjusting for patient characteristics. CONCLUSION:
      Adjustment for patient differences may produce a more fair comparison between
      GPs, but may also blur the assessment of GPs' ability to meet the needs of the
      populations actually served. On the other hand, adjusted results will enable us
      to describe the significance of specific patient characteristics to patients'
      experience of care.

PMID- 18715503
TI  - A nitty-gritty aspect of correlation and network inference from gene expression
      data.
AB  - BACKGROUND: All currently available methods of network/association inference from
      microarray gene expression measurements implicitly assume that such measurements
      represent the actual expression levels of different genes within each cell
      included in the biological sample under study. Contrary to this common belief,
      modern microarray technology produces signals aggregated over a random number of
      individual cells, a "nitty-gritty" aspect of such arrays, thereby causing a
      random effect that distorts the correlation structure of intra-cellular gene
      expression levels. RESULTS: This paper provides a theoretical consideration of
      the random effect of signal aggregation and its implications for correlation
      analysis and network inference. An attempt is made to quantitatively assess the
      magnitude of this effect from real data. Some preliminary ideas are offered to
      mitigate the consequences of random signal aggregation in the analysis of gene
      expression data. CONCLUSION: Resulting from the summation of expression
      intensities over a random number of individual cells, the observed signals may
      not adequately reflect the true dependence structure of intra-cellular gene
      expression levels needed as a source of information for network reconstruction.
      Whether the reported effect is extrime or not, the important point, is to
      reconize and incorporate such signal source for proper inference. The usefulness
      of inference on genetic regulatory structures from microarray data depends
      critically on the ability of investigators to overcome this obstacle in a
      scientifically sound way. REVIEWERS: This article was reviewed by Byung Soo KIM,
      Jeanne Kowalski and Geoff McLachlan.

PMID- 18715504
TI  - Rapid functional diversification in the structurally conserved ELAV family of
      neuronal RNA binding proteins.
AB  - BACKGROUND: The Drosophila gene embryonic lethal abnormal visual system (elav) is
      the prototype of a gene family present in all metazoans. Its members encode
      structurally conserved neuronal proteins with three RNA Recognition Motifs (RRM)
      but they paradoxically act at diverse levels of post-transcriptional regulation.
      In an attempt to understand the history of this family, we searched for orthologs
      in eleven completely sequenced genomes, including those of humans, D.
      melanogaster and C. elegans, for which cDNAs are available. RESULTS: We analyzed
      23 orthologs/paralogs of elav, and found evidence of gain/loss of gene copy
      number. For one set of genes, including elav itself, the coding sequences are
      free of introns and their products most resemble ELAV. The remaining genes show
      remarkable conservation of their exon organization, and their products most
      resemble FNE and RBP9, proteins encoded by the two elav paralogs of Drosophila.
      Remarkably, three of the conserved exon junctions are both close to structural
      elements, involved respectively in protein-RNA interactions and in the regulation
      of sub-cellular localization, and in the vicinity of diverse sequence variations.
      CONCLUSION: The data indicate that the essential elav gene of Drosophila is newly
      emerged, restricted to dipterans and of retrotransposed origin. We propose that
      the conserved exon junctions constitute potential sites for sequence/function
      modifications, and that RRM binding proteins, whose function relies upon plastic
      RNA-protein interactions, may have played an important role in brain evolution.

PMID- 18715505
TI  - Perianal squamous cell carcinoma in-situ: a report of two human papilloma virus
      negative cases.
AB  - We are reporting two cases of perianal squamous cell carcinoma in-situ, negative
      for high-risk (HR) and low-risk (LR) human papilloma viruses. A brief review of
      anal and perianal squamous cell carcinoma and the role of HPV are presented.

PMID- 18715506
TI  - Diversity in genomic organisation, developmental regulation and distribution of
      the murine PR72/B" subunits of protein phosphatase 2A.
AB  - BACKGROUND: Protein phosphatase 2A (PP2A) is a serine/threonine-specific
      phosphatase displaying vital functions in growth and development through its role
      in various signalling pathways. PP2A holoenzymes comprise a core dimer composed
      of a catalytic C and a structural A subunit, which can associate with a variable
      B-type subunit. The importance of the B-type subunits for PP2A regulation cannot
      be overestimated as they determine holoenzyme localisation, activity and
      substrate specificity. Three B-type subunit families have been identified:
      PR55/B, PR61/B' and PR72/B", of which the latter is currently the least
      characterised. RESULTS: We deduced the sequences and genomic organisation of the
      different murine PR72/B" isoforms: three genes encode nine isoforms, five of
      which are abundantly expressed and give rise to genuine PP2A subunits. Thereby,
      one novel subunit was identified. Using Northern blotting, we examined the tissue
      specific and developmental expression of these subunits. All subunits are highly
      expressed in heart, suggesting an important cardiac function. Immunohistochemical
      analysis revealed a striated expression pattern of PR72 and PR130 in heart and
      skeletal muscle, but not in bladder smooth muscle. The subcellular localisation
      and cell cycle regulatory ability of several PR72/B" isoforms were determined,
      demonstrating differences as well as similarities. CONCLUSION: In contrast to
      PR55/B and PR61/B', the PR72/B" family seems evolutionary more divergent, as only
      two of the murine genes have a human orthologue. We have integrated these results
      in a more consistent nomenclature of both human and murine PR72/B" genes and
      their transcripts/proteins. Our results provide a platform for the future
      generation of PR72/B" knockout mice.

PMID- 18715507
TI  - Association of alleles carried at TNFA -850 and BAT1 -22 with Alzheimer's
      disease.
AB  - BACKGROUND: Inflammatory changes are a prominent feature of brains affected by
      Alzheimer's disease (AD). Activated glial cells release inflammatory cytokines
      which modulate the neurodegenerative process. These cytokines are encoded by
      genes representing several interleukins and TNFA, which are associated with AD.
      The gene coding for HLA-B associated transcript 1 (BAT1) lies adjacent to TNFA in
      the central major histocompatibility complex (MHC). BAT1, a member of the DEAD
      box family of RNA helicases, appears to regulate the production of inflammatory
      cytokines associated with AD pathology. In the current study TNFA and BAT1
      promoter polymorphisms were analysed in AD and control cases and BAT1 mRNA levels
      were investigated in brain tissue from AD and control cases. METHODS: Genotyping
      was performed for polymorphisms at positions -850 and -308 in the proximal
      promoter of TNFA and position -22 in the promoter of BAT1. These were
      investigated singly or in haplotypic association in a cohort of Australian AD
      patients with AD stratified on the basis of their APOE epsilon4 genotype. Semi
      quantitative RT-PCR was also performed for BAT1 from RNA isolated from brain
      tissue from AD and control cases. RESULTS: APOE epsilon4 was associated with an
      independent increase in risk for AD in individuals with TNFA -850*2, while
      carriage of BAT1 -22*2 reduced the risk for AD, independent of APOE epsilon4
      genotype. Semi-quantitative mRNA analysis in human brain tissue showed elevated
      levels of BAT1 mRNA in frontal cortex of AD cases. CONCLUSION: These findings
      lend support to the application of TNFA and BAT1 polymorphisms in early diagnosis
      or risk assessment strategies for AD and suggest a potential role for BAT1 in the
      regulation of inflammatory reactions in AD pathology.

PMID- 18715508
TI  - Establishment of a large semi-field system for experimental study of African
      malaria vector ecology and control in Tanzania.
AB  - BACKGROUND: Medical entomologists increasingly recognize that the ability to make
      inferences between laboratory experiments of vector biology and epidemiological
      trends observed in the field is hindered by a conceptual and methodological gap
      occurring between these approaches which prevents hypothesis-driven empirical
      research from being conducted on relatively large and environmentally realistic
      scales. The development of Semi-Field Systems (SFS) has been proposed as the best
      mechanism for bridging this gap. Semi-field systems are defined as enclosed
      environments, ideally situated within the natural ecosystem of a target disease
      vector and exposed to ambient environmental conditions, in which all features
      necessary for its life cycle completion are present. Although the value of SFS as
      a research tool for malaria vector biology is gaining recognition, only a few
      such facilities exist worldwide and are relatively small in size (< 100 m2).
      METHODS: The establishment of a 625 m2 state-of-the-art SFS for large-scale
      experimentation on anopheline mosquito ecology and control within a rural area of
      southern Tanzania, where malaria transmission intensities are amongst the highest
      ever recorded, is described. RESULTS: A greenhouse frame with walls of mosquito
      netting and a polyethylene roof was mounted on a raised concrete platform at the
      Ifakara Health Institute. The interior of the SFS was divided into four separate
      work areas that have been set up for a variety of research activities including
      mass-rearing for African malaria vectors under natural conditions, high
      throughput evaluation of novel mosquito control and trapping techniques, short
      term assays of host-seeking behaviour and olfaction, and longer-term experimental
      investigation of anopheline population dynamics and gene flow within a contained
      environment that simulates a local village domestic setting. CONCLUSION: The SFS
      at Ifakara was completed and ready for use in under two years. Preliminary
      observations indicate that realistic and repeatable observations of anopheline
      behaviour are obtainable within the SFS, and that habitat and climatic features
      representative of field conditions can be simulated within it. As work begins in
      the SFS in Ifakara and others around the world, the major opportunities and
      challenges to the successful application of this tool for malaria vector research
      and control are discussed.

PMID- 18715511
TI  - Genetic structure and breeding system in a social wasp and its social parasite.
AB  - BACKGROUND: Social insects dominate ecological communities because of their
      sophisticated group behaviors. However, the intricate behaviors of social insects
      may be exploited by social parasites, which manipulate insect societies for their
      own benefit. Interactions between social parasites and their hosts lead to
      unusual coevolutionary dynamics that ultimately affect the breeding systems and
      population structures of both species. This study represents one of the first
      attempts to understand the population and colony genetic structure of a parasite
      and its host in a social wasp system. RESULTS: We used DNA microsatellite markers
      to investigate gene flow, genetic variation, and mating behavior of the
      facultative social parasite Vespula squamosa and its primary host, V.
      maculifrons. Our analyses of genetic variability uncovered that both species
      possessed similar amounts of genetic variation and failed to show genetic
      structure over the sampling area. Our analysis of mating system of V. maculifrons
      and V. squamosa revealed high levels of polyandry and no evidence for inbreeding
      in the two species. Moreover, we found no significant differences between
      estimates of worker relatedness in this study and a previous investigation
      conducted over two decades ago, suggesting that the selective pressures operating
      on queen mate number have remained constant. Finally, the distribution of queen
      mate number in both species deviated from simple expectations suggesting that
      mate number may be under stabilizing selection. CONCLUSION: The general biology
      of V. squamosa has not changed substantially from that of a typical, nonparasitic
      Vespula wasp. For example, population sizes of the host and its parasite appear
      to be similar, in contrast to other social parasites, which often display lower
      population sizes than their hosts. In addition, parasitism has not caused the
      mating behavior of V. squamosa queens to deviate from the high levels of multiple
      mating that typify Vespula wasps. This stands in contrast to some socially
      parasitic ants, which revert to mating with few males. Overall, the general
      similarity of the genetic structure of V. maculifrons and V. squamosa presumably
      reflects the fact that V. squamosa is still capable of independent colony
      founding and thus reflects an intermediate stage in the evolution of social
      parasitism.

PMID- 18715510
TI  - The importance of rectal cancer MRI protocols on interpretation accuracy.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is used for preoperative local
      staging in patients with rectal cancer. Our aim was to retrospectively study the
      effects of the imaging protocol on the staging accuracy. PATIENTS AND METHODS: MR
      examinations of 37 patients with locally advanced disease were divided into two
      groups; compliant and noncompliant, based on the imaging protocol, without
      knowledge of the histopathological results. A compliant rectal cancer imaging
      protocol was defined as including T2-weighted imaging in the sagittal and axial
      planes with supplementary coronal in low rectal tumors, alongside a high
      resolution plane perpendicular to the rectum at the level of the primary tumor.
      Protocols not complying with these criteria were defined as noncompliant.
      Histopathological results were used as gold standard. RESULTS: Compliant rectal
      imaging protocols showed significantly better correlation with histopathological
      results regarding assessment of anterior organ involvement (sensitivity and
      specificity rates in compliant group were 86% and 94%, respectively vs. 50% and
      33% in the noncompliant group). Compliant imaging protocols also used
      statistically significantly smaller voxel sizes and fewer number of MR sequences
      than the noncompliant protocols CONCLUSION: Appropriate MR imaging protocols
      enable more accurate local staging of locally advanced rectal tumors with less
      number of sequences and without intravenous gadolinium contrast agents.

PMID- 18715509
TI  - Extracting key information from historical data to quantify the transmission
      dynamics of smallpox.
AB  - BACKGROUND: Quantification of the transmission dynamics of smallpox is crucial
      for optimizing intervention strategies in the event of a bioterrorist attack.
      This article reviews basic methods and findings in mathematical and statistical
      studies of smallpox which estimate key transmission parameters from historical
      data. MAIN FINDINGS: First, critically important aspects in extracting key
      information from historical data are briefly summarized. We mention different
      sources of heterogeneity and potential pitfalls in utilizing historical records.
      Second, we discuss how smallpox spreads in the absence of interventions and how
      the optimal timing of quarantine and isolation measures can be determined. Case
      studies demonstrate the following. (1) The upper confidence limit of the 99th
      percentile of the incubation period is 22.2 days, suggesting that quarantine
      should last 23 days. (2) The highest frequency (61.8%) of secondary transmissions
      occurs 3-5 days after onset of fever so that infected individuals should be
      isolated before the appearance of rash. (3) The U-shaped age-specific case
      fatality implies a vulnerability of infants and elderly among non-immune
      individuals. Estimates of the transmission potential are subsequently reviewed,
      followed by an assessment of vaccination effects and of the expected
      effectiveness of interventions. CONCLUSION: Current debates on bio-terrorism
      preparedness indicate that public health decision making must account for the
      complex interplay and balance between vaccination strategies and other public
      health measures (e.g. case isolation and contact tracing) taking into account the
      frequency of adverse events to vaccination. In this review, we summarize what has
      already been clarified and point out needs to analyze previous smallpox outbreaks
      systematically.

PMID- 18715512
TI  - Antimicrobial activity of some sulfonamide derivatives on clinical isolates of
      Staphylococus aureus.
AB  - BACKGROUND: Staphylococcus aureus is a non-motile, gram positive, non
      sporforming, facultative anaerobic microorganism. It is one of the important
      bacteria as a potential pathogen specifically for nosocomial infections. The
      sulfonamide derivative medicines are preferred to cure infection caused by S.
      aureus due to methicillin resistance. METHODS: Antimicrobial activity of four
      sulfonamide derivatives have been investigated against 50 clinical isolates of S.
      aureus and tested by using MIC and disc diffusion methods. 50 clinical isolate
      which collected from specimens of patients who are given medical treatment in
      Ondokuz Mayis University Medical School Hospital. A control strain of S. aureus
      ATCC 29213 was also tested. RESULTS: The strongest inhibition was observed in the
      cases of I [N-(2-hydroxy-4-nitro-phenyl)-4-methyl-benzensulfonamid], and II [N-(2
      hydroxy-5-nitro-phenyl)-4-methyl-benzensulfonamid] against S. aureus. Compound I
      [N-(2-hydroxy-4-nitro-phenyl)-4-methyl-benzensulfonamid] showed higher effect on
      21 S. aureus MRSAisolates than oxacillin antibiotic. Introducing an electron
      withdrawing on the ring increased the antimicrobial activity remarkably.
      CONCLUSION: This study may help to suggest an alternative possible leading
      compound for development of new antimicrobial agents against MRSA and MSSA
      resistant S. aureus. It was also shown here that that clinical isolates of 50 S.
      aureus have various resistance patterns against to four sulfonamide derivatives.
      It may also be emphasized here that in vitro antimicrobial susceptibility testing
      results for S. aureus need standardization with further studies and it should
      also have a correlation with in vivo therapeutic response experiments.

PMID- 18715513
TI  - Six Mantoux tuberculin skin tests with 1, 2, 5, 10, 20, and 50 units in a healthy
      male without side-effects - is skin reaction a linear function of tuberculin
      dose?
AB  - BACKGROUND: Tuberculosis remains a serious disease worldwide. Anti-tuberculosis
      campaigners many times face negative tuberculin skin tests after Bacille Calmette
      Guerin vaccination. Increasing tuberculin units might be a solution. However, is
      skin reaction a linear function of tuberculin dose? Are there any side-effects
      when higher tuberculin doses are administered? CASE PRESENTATION: Six
      simultaneous Mantoux tuberculin skin tests, using 1, 2, 5, 10, 20, and 50
      tuberculin units (88 altogether) of purified protein derivative RT23 per 0.1 mL
      were applied in a healthy male Greek 35-years-old, with known natural
      Mycobacterium tuberculosis primary infection since five years. Skin indurations
      72 hours later were 15, 22, 23, 19, 23, and 27 mm respectively. CONCLUSION: No
      linear relation between tuberculin dose and skin reaction observed; skin reaction
      increased as tuberculin dose increased but with a decreasing rate, especially
      after 2 TUs, which seem correctly defined for detection of natural infection. No
      side-effects occurred.

PMID- 18715514
TI  - Arterial pressure changes monitoring with a new precordial noninvasive sensor.
AB  - BACKGROUND: Recently, a cutaneous force-frequency relation recording system based
      on first heart sound amplitude vibrations has been validated. A further
      application is the assessment of Second Heart Sound (S2) amplitude variations at
      increasing heart rates. The aim of this study was to assess the relationship
      between second heart sound amplitude variations at increasing heart rates and
      hemodynamic changes. METHODS: The transcutaneous force sensor was positioned in
      the precordial region in 146 consecutive patients referred for exercise (n = 99),
      dipyridamole (n = 41), or pacing stress (n = 6). The curve of S2 peak amplitude
      variation as a function of heart rate was computed as the increment with respect
      to the resting value. RESULTS: A consistent S2 signal was obtained in all
      patients. Baseline S2 was 7.2 +/- 3.3 mg, increasing to 12.7 +/- 7.7 mg at peak
      stress. S2 percentage increase was + 133 +/- 104% in the 99 exercise, + 2 +/- 22%
      in the 41 dipyridamole, and + 31 +/- 27% in the 6 pacing patients (p < 0.05).
      Significant determinants of S2 amplitude were blood pressure, heart rate, and
      cardiac index with best correlation (R = .57) for mean pressure. CONCLUSION: S2
      recording quantitatively documents systemic pressure changes.

PMID- 18715515
TI  - Lack of evidence for association of primary sclerosing cholangitis and primary
      biliary cirrhosis with risk alleles for Crohn's disease in Polish patients.
AB  - BACKGROUND: Numerous papers have addressed the association of mutations and
      polymorphisms of susceptibility genes with autoimmune inflammatory disorders. We
      investigated whether polymorphisms that confer susceptibility to Crohn's disease
      could be classified also as predisposing factors for the development of primary
      sclerosing cholangitis and primary biliary cirrhosis in Polish patients. METHODS:
      The study included 60 patients with CD, 77 patients with PSC, of which 61
      exhibited IBD (40 UC, 8 CD, and 13 indeterminate colitis), and 144 patients with
      PBC. All the patients were screened against Crohn's disease associating genetic
      polymorphisms. The polymorphisms were chosen according to previously confirmed
      evidence for association with Crohn's disease, including Pro268Ser, Arg702Trp,
      Gly908Arg and 1007fs in NOD2/CARD15, Leu503Phe/-207G>C in
      SLC22A4/OCTN1/SLC22A5/OCTN2, Arg30Gln in DLG5, Thr300Ala in ATG16L1, and
      Arg381Gln, His3Gln and exon-3'UTR in IL23R. Genotyping was carried out using
      TaqMan SNP genotyping assays. RESULTS: We confirmed a strong association between
      three NOD2/CARD15 gene variants (Pro268Ser, OR = 2.52, 95% CI = 1.34-4.75);
      (Arg702Trp, OR = 6.65, 95% CI = 1.99-22.17); (1007fs, OR = 9.59, 95% CI = 3.94
      23.29), and a weak association between both the protective OCTN1/OCTN2 CC
      haplotype (OR = 0.28, 95% CI = 0.08-0.94), and a variant of ATG16L1 gene
      (Thr300Ala, OR = 0.468, 95% CI = 0.24-0.90) with Crohn's disease. In contrast,
      none of the polymorphisms exhibited association with susceptibility to primary
      sclerosing cholangitis and primary biliary cirrhosis, including a group of
      primary sclerosing cholangitis patients with concurrent IBD. CONCLUSION: Although
      the clinical data indicate non-random co-occurrence of inflammatory bowel disease
      and primary sclerosing cholangitis, consistently with the previously published
      studies, no genetic association was found between the genetic variants
      predisposing to Crohn's disease and hepatobiliary autoimmune disorders. However,
      since estimation of genetic variant disproportion is limited by sample size,
      these negative results may also indicate that eventually shared genetic
      predispositions are too little to be captured by small patient groups.

PMID- 18715517
TI  - Models and mechanisms of energy balance regulation in the young.
AB  - The proportion of the child and adolescent population that is in appropriate
      energy balance is declining throughout the developed world, and childhood obesity
      is a particular problem in the UK relative to other northern European countries.
      Assessment of the underlying causes of obesity, and the different routes to its
      development, may assist in the definition of successful intervention strategies.
      The network of peripheral and central (brain) regulatory systems that underlie
      energy balance and body weight and composition can, for the most part, only be
      approached experimentally through the study of appropriate laboratory animal
      models. This problem is particularly acute when the target is overweight and
      obesity in the young. Some of the mechanisms underlying the development of energy
      imbalance and specifically the onset of overweight and obesity in the young, and
      the metabolic health consequences of obesity, can be addressed by examination of
      experimental rodent models in which mutation of a single gene causes early-onset
      extreme obesity, genetic susceptibility to obesity is revealed in an obesogenic
      environment or early-life nutritional experience programmes susceptibility to
      obesity or metabolic problems in later life. These studies highlight genes that
      are essential to normal body-weight regulation in rodents and man, the impact of
      diet and diet-induced obesity on regulatory systems in the young and the
      potential sensitivity of developing regulatory systems to nutritional experiences
      in utero and during early life.

PMID- 18715516
TI  - Can the feedback of patient assessments, brief training, or their combination,
      improve the interpersonal skills of primary care physicians? A systematic review.
AB  - BACKGROUND: Improving quality of primary care is a key focus of international
      health policy. Current quality improvement efforts place a large focus on
      technical, clinical aspects of quality, but a comprehensive approach to quality
      improvement should also include interpersonal care. Two methods of improving the
      quality of interpersonal care in primary care have been proposed. One involves
      the feedback of patient assessments of interpersonal care to physicians, and the
      other involves brief training and education programmes. This study therefore
      reviewed the efficacy of (i) feedback of real patient assessments of
      interpersonal care skills, (ii) brief training focused on the improvement of
      interpersonal care (iii) interventions combining both (i) and (ii) METHODS:
      Systematic review of randomised controlled trials. Three electronic databases
      were searched (CENTRAL, Medline and Embase) and augmented by searches of the
      bibliographies of retrieved articles. The quality of studies was appraised and
      results summarised in narrative form. RESULTS: Nine studies were included (two
      patient based feedback studies and seven brief training studies). Of the two
      feedback studies, one reported a significant positive effect. Only one training
      study reported a significant positive effect. CONCLUSION: There is limited
      evidence concerning the effects of patient based feedback. There is reasonable
      evidence that brief training as currently delivered is not effective, although
      the evidence is not definitive, due to the small number of trials and the
      variation in the training methods and goals. The lack of effectiveness of these
      methods may reflect a number of issues, such as differences in the effectiveness
      of the interventions in experienced practitioners and those in training, the lack
      of theory linking feedback to behaviour change, failure to provide sufficient
      training or to use a comprehensive range of behaviour change techniques. Further
      research into both feedback and brief training interventions is required before
      these interventions are routinely introduced to improve patient satisfaction with
      interpersonal care in primary care. The interventions to be tested in future
      research should consider using insights from the wider literature on
      communication outside primary care, might benefit from a clearer theoretical
      basis, and should examine the use of combined brief training and feedback.

PMID- 18715518
TI  - Effects of dietary fibre on behaviour and satiety in pigs.
AB  - During the past decades there has been considerable interest in the use of
      dietary fibre in both animal and human nutrition. In human subjects dietary fibre
      has been studied intensively for possible effects on body-weight management and
      health. In animal nutrition the interest in dietary fibre has increased because
      it can be used as a cheap source of energy and because of its potential to
      improve animal welfare and reduce abnormal (mainly stereotypic) behaviour. Animal
      welfare is impaired if the diet does not provide sufficient satiety, combined
      with an environment that does not meet specific behavioural requirements related
      to natural feeding habits (e.g. rooting in pigs). A considerable proportion of
      the behavioural effects of dietary fibre are thought to be related to reduced
      feeding motivation. It has been hypothesized that: (1) bulky fibres increase
      satiety and thereby decrease physical activity and stereotypic behaviours
      immediately following a meal in pigs; (2) fermentable fibres prolong postprandial
      satiety and thereby reduce physical activity and appetitive behaviours for many
      hours after a meal. The validity of these hypotheses is examined by considering
      published data. In sows dietary fibres (irrespective of source) reduce
      stereotypic self-directed behaviours and substrate-directed behaviours, and to a
      lesser extent overall physical activity, indicating enhanced satiety shortly
      after a meal. Furthermore, fermentable dietary fibre reduces substrate-directed
      behaviour in sows and physical activity in sows and growing pigs for many hours
      after a meal. Evidence of long-term effects of poorly-fermentable fibre sources
      is inconclusive. The findings suggest that highly-fermentable dietary fibres have
      a higher potential to prolong postprandial satiety.

PMID- 18715519
TI  - Appetitive traits and child obesity: measurement, origins and implications for
      intervention.
AB  - Childhood obesity has multiple causes, most of them capable of explaining only
      one part of the problem. The population-wide impact of sedentary lifestyles and
      availability of energy-dense food is undeniable, but substantial individual
      differences in body weight persist, suggesting that individuals respond
      differently to the 'obesogenic' environment. One plausible mechanism for this
      variation is the early expression of appetitive traits, including low
      responsiveness to internal satiety signals, high responsiveness to external food
      cues, high subjective reward experienced when eating liked foods and preferences
      for energy-dense foods. Case-control studies support the existence of
      abnormalities in these traits among obese children compared with normal-weight
      children, and correlations between psychometric measures of child appetite and
      child weight suggest that appetitive trait profiles may not only promote obesity
      but also protect against it. The origins of appetitive traits are as yet
      uncharted, but will include both genetic and environmental influences. Parental
      feeding style may affect the development of appetite but the exact nature of the
      relevant behaviours is unclear and many studies are cross-sectional or begin late
      in childhood, obscuring causal relationships. Future research should explore
      determinants and biological mechanisms by using prospective designs beginning
      early in life, measuring relevant biomarkers such as gut hormones and
      incorporating neuroimaging and genotyping technologies. Potential clinical
      applications include the identification of 'at risk' children early in life and
      interventions to modify appetitive traits or ameliorate their impact on intake
      and weight.

PMID- 18715520
TI  - Childhood obesity: from nutrition to behaviour.
AB  - Obesity in children is difficult to treat, but it seems to be easier to treat
      than adult obesity. The first step in treatment is to identify effective advice
      relating to nutrition and physical activity. In most treatment studies the
      macronutrient composition of the diet is not of major importance for treatment
      outcome. In relation to physical activity fat-utilisation strategies have been
      described. The second step includes appropriate approaches to lifestyle change.
      In Europe there are no drugs approved for children, and surgery for children is
      still limited to research projects. Thus, the major challenge is to develop
      effective ways of changing lifestyle. Family therapy may be an effective approach
      in preventing severe obesity from developing during puberty, and a therapeutic
      strategy based on treatment studies is described. The family-therapy techniques
      used here are intended to facilitate the family's own attempts to modify their
      lifestyle, and to increase their own sense of responsibility and readiness to
      change, i.e. these variables are the prime targets during therapy. Thus, the
      family, not the therapist, assumes responsibility for the changes achieved. This
      approach may be helpful in making the therapeutic process less cumbersome for the
      therapist. Instead of the therapist attempting to persuade the obese subjects to
      lose weight, it might be more effective to teach them to control their eating
      patterns through their own efforts. The treatment model includes structural
      family therapy and solution-focused-brief therapy. The use of such a model makes
      it possible to train therapists and health professionals to use an evidence-based
      intervention model.

PMID- 18715521
TI  - Session 1: Public health nutrition. Breast-feeding practices in Ireland.
AB  - Breast-feeding is the superior infant feeding method from birth, with research
      consistently demonstrating its numerous short- and long-term health benefits for
      both mother and infant. As a global recommendation the WHO advises that mothers
      should exclusively breast-feed for the first 6-months of life, thus delaying the
      introduction of solids during this time. Historically, Irish breast-feeding
      initiation rates have remained strikingly low in comparison with international
      data and there has been little improvement in breast-feeding duration rates.
      There is wide geographical variation in terms of breast-feeding initiation both
      internationally and in Ireland. Some of these differences in breast-feeding rates
      may be associated with differing socio-economic characteristics. A recent cross
      sectional prospective study of 561 pregnant women attending a Dublin hospital and
      followed from the antenatal period to 6 months post partum has found that 47% of
      the Irish-national mothers initiated breast-feeding, while only 24% were still
      offering 'any' breast milk to their infants at 6 weeks. Mothers' positive
      antenatal feeding intention to breast-feed is indicated as one of the most
      important independent determinants of initiation and 'any' breast-feeding at 6
      weeks, suggesting that the antenatal period should be targeted as an effective
      time to influence and affect mothers' attitudes and beliefs pertaining to breast
      feeding. These results suggest that the 'cultural' barrier towards breast-feeding
      appears to still prevail in Ireland and consequently an environment that enables
      women to breast-feed is far from being achieved. Undoubtedly, a shift towards a
      more positive and accepting breast-feeding culture is required if national breast
      feeding rates are to improve.

PMID- 18715522
TI  - Cryptic species within Anopheles longipalpis from southern Africa and
      phylogenetic comparison with members of the An. funestus group.
AB  - House-resting Anopheles mosquitoes are targeted for vector control interventions;
      however, without proper species identification, the importance of these Anopheles
      to malaria transmission is unknown. Anopheles longipalpis, a non-vector species,
      has been found in significant numbers resting indoors in houses in southern
      Zambia, potentially impacting on the utilization of scarce resources for vector
      control. The identification of An. longipalpis is currently based on classical
      morphology using minor characteristics in the adult stage and major ones in the
      larval stage. The close similarity to the major malaria vector An. funestus led
      to investigations into the development of a molecular assay for identification of
      An. longipalpis. Molecular analysis of An. longipalpis from South Africa and
      Zambia revealed marked differences in size and nucleotide sequence in the second
      internal transcribed spacer (ITS2) region of ribosomal DNA between these two
      populations, leading to the conclusion that more than one species was being
      analysed. Phylogenetic analysis showed the Zambian samples aligned with An.
      funestus, An. vaneedeni and An. parensis, whereas the South African sample
      aligned with An. leesoni, a species that is considered to be more closely related
      to the Asian An. minimus subgroup than to the African An. funestus subgroup.
      Species-specific primers were designed to be used in a multiplex PCR assay to
      distinguish between these two cryptic species and members of the An. funestus
      subgroup for which there is already a multiplex PCR assay.

PMID- 18715524
TI  - Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban
      in healthy elderly subjects.
AB  - OBJECTIVE: The aim of this study was to investigate the pharmacokinetics and
      pharmacodynamics of rivaroxaban--a novel, oral, direct Factor Xa (FXa) inhibitor-
      in healthy elderly subjects. RESEARCH DESIGN AND METHODS: In this single-centre,
      single-blind, placebo-controlled, parallel-group, dose-escalation study, 48
      subjects (aged 60-76 years) were randomized to receive a single oral dose of 30,
      40 or 50 mg of rivaroxaban or placebo. RESULTS: Rivaroxaban was absorbed rapidly,
      reaching peak plasma concentration (C(max)) 4 h after dosing in all groups.
      Bioavailability, in terms of the area under the plasma concentration-time curve
      (AUC) and C(max), increased slightly (less than dose proportionally) after
      administration of rivaroxaban 40 mg compared with 30 mg, but was not increased
      further with rivaroxaban 50 mg. Rivaroxaban pharmacodynamic effects (inhibition
      of FXa activity and prolongation of prothrombin time, activated partial
      thromboplastin time and HepTest) all showed a similar pattern, with maximum
      inhibition of FXa activity increasing from 68% after rivaroxaban 30 mg to 75%
      after 40 mg and no further increase with the 50 mg dose. Most adverse events were
      mild; observed rates were less than placebo for the 30 and 40 mg dose groups, and
      similar to placebo for 50 mg. No differences were found between male and female
      subjects. Effects of rivaroxaban doses above 50 mg were not investigated in this
      study. CONCLUSIONS: Each single dose of rivaroxaban was well tolerated, with
      predictable pharmacokinetics and pharmacodynamics at doses up to 40 mg, and
      provided effective anticoagulation in healthy elderly subjects. Adverse events
      were somewhat elevated in the 50 mg group, but given the small sample size, no
      specific conclusions can be drawn about this dosing level.

PMID- 18715523
TI  - Echinococcus granulosus strain differentiation in Iran based on sequence
      heterogeneity in the mitochondrial 12S rRNA gene.
AB  - Parasite strain characterization is essential for the establishment of a
      prevention and control strategy in any endemic area. The aim of this study was to
      characterize different Echinococcus granulosus isolates from Iran by using DNA
      sequences of the mitochondrial 12S rRNA gene. Thirty livers and lungs of cattle,
      sheep and goats naturally infected with E. granulosus were collected from
      abattoirs in northern and western Iran between June and October 2007. These
      samples yielded 18 fertile cysts which we used for the genetic work. We designed
      and tested two new primer pairs which specifically amplify portions of the
      mitochondrial 12S rRNA gene of the two strains (G1 and G6) of E. granulosus known
      to occur in Iran. One primer pair amplified a fragment of 259 base pairs (bp)
      from only the G1 strain. The second pair amplified a fragment of 676 bp from the
      G6 strain. The G1 genotype was identified in all fertile cyst samples, in
      agreement with previous studies in Iran. Ten of our samples and a single
      reference sample of the G6 strain were sequenced and compared with the G1 and G6
      sequences deposited in GenBank.

PMID- 18715525
TI  - Usability of a pre-filled insulin injection device in a 3-month observational
      survey of everyday clinical practice in Australia.
AB  - OBJECTIVE: SoloSTAR (SR) is a new pre-filled insulin pen device for
      administration of insulin glargine and insulin glulisine. This article reports on
      the usability of SR, as reported by healthcare professionals (HCPs) and
      participants, in clinical practice in Australia. METHODS: Individuals with Type 1
      or Type 2 diabetes were eligible for this 3-month observational survey.
      Participants were supplied with the insulin glargine SR pens, the instruction
      leaflet and a toll-free helpline number. Training was offered to all
      participants. Independent telephone interviews were conducted with participants
      and HCPs after 6-10 weeks of use of SR. RESULTS: Overall, 150 HCPs across 93
      sites supported this survey. Of these, 65 HCPs (14 doctors; 51 diabetes
      educators, covering 1669 patients) provided feedback, with the remaining 85 HCPs
      not responding. All HCPs rated participant training as 'very easy' or 'easy', and
      most reported that SR had, in their opinion, made training easier (85%) and
      quicker (98%). Most of the 536 participants reported that ease of learning to use
      (98%), ease of using (98%) and features (> or = 89%) of SR were 'excellent' or
      'good'. SR had positive impacts on various psychological aspects for people with
      diabetes, including helping overcome reluctance to use insulin, and increasing
      confidence in their ability to manage their diabetes using insulin. CONCLUSIONS:
      In this non-randomized, non-interventional, open-label, observational survey of
      clinical practice, HCPs reported that SR was easy to teach and easy to use for
      people with diabetes. People with diabetes reported that SR was easy to use and
      rated specific features of SR highly. Further follow-up surveys and comparative
      studies in clinical practice are needed to confirm these findings and to
      determine the impact of SR in diabetes management.

PMID- 18715526
TI  - Health-related quality of life of immune thrombocytopenic purpura patients:
      results from a web-based survey.
AB  - OBJECTIVE: To assess the health-related quality of life (HRQOL) of immune
      thrombocytopenic purpura (ITP) patients. RESEARCH DESIGN AND METHODS: This was a
      cross-sectional, descriptive study comparing ITP patients' HRQOL to age and
      gender matched controls. ITP patients from the Platelet Disorder Support
      Association were recruited until 1000 surveys had been completed. Controls were
      randomly sampled from the Harris Interactive Online Panel. ITP patients and
      controls completed a one-time web-based survey, including a comprehensive HRQOL
      assessment. ITP patients completed the SF-36, the EQ-5D, and the ITP-Patient
      Assessment Questionnaire (ITP-PAQ). Controls completed the SF-36 and EQ-5D only.
      ITP patients' SF-36 and EQ-5D scores were compared to controls in unadjusted and
      adjusted analyses. Associations between splenectomy status, duration of illness,
      and platelet count with ITP patients' HRQOL scores were also examined. RESULTS:
      This analysis included 1002 ITP patients and 1031 controls. ITP patients scored
      worse on seven of eight SF-36 domains and the Physical and Mental Summary scores
      (all p < 0.05) and on the EQ-5D visual analog scale (65.5 vs. 82.3; p = 0.002).
      ITP patients who had undergone splenectomy had similar SF-36 and EQ-5D scores to
      non-splenectomy patients but scored significantly worse on 5 of 10 ITP-PAQ
      scales: Bother, Psychological, Fear, Social Activity, and Work (all p < 0.05).
      ITP patients diagnosed within the past 5 years had worse Bother and Overall
      Quality of Life scores than less recently diagnosed patients but were similar on
      other ITP-PAQ scales. Lower platelet count was consistently associated with worse
      ITP-PAQ scores and had weaker associations with SF-36 and EQ-5D scores.
      CONCLUSIONS: ITP was associated with consistent and statistically significant
      deficits on generic HRQOL measures. The ITP-PAQ demonstrated differences based on
      disease severity and treatments. The self-selection bias in the two samples
      limits the generalizability of the results to all patients with ITP. Further
      research is needed in more generalizable samples.

PMID- 18715527
TI  - Hemoglobin levels that trigger erythropoiesis-stimulating agent treatment
      decisions for cancer-associated anemia--examination of practice in Germany.
AB  - OBJECTIVE: Given the safety concerns regarding off-label use of erythropoiesis
      stimulating agents (ESAs) in the treatment of cancer-associated anemia, data from
      the German Cancer Anemia Registry (CAR) were analyzed to examine whether current
      practice in Germany adheres to treatment guidelines. RESEARCH DESIGN AND METHODS:
      CAR was a web-based registry gathering patient data for 12 weeks following anemia
      diagnosis or until the primary treatment objective was achieved. RESULTS: Of over
      2000 patients surveyed, 783 were treated with ESAs. Treatment was primarily aimed
      at improvement of quality of life (37.3%), hemoglobin correction (32.7%), and
      prevention of transfusions (24.4%). The average hemoglobin level triggering ESA
      treatment was 9.7 g/dL (6.0 mmol/L), however, starting levels varied with cancer
      type. For 67.8% of patients, transfusions could be avoided. ESA treatment was
      stopped at 11.2 g/dL (7.0 mmol/L) and maximum hemoglobin levels during the study
      averaged 11.8 g/dL (7.3 mmol/L). In 4.8% of the women and 6.0% of the men,
      maximum hemoglobin levels were >14 g/dL (8.7 mmol/L); in 15.6% and 9.1%,
      respectively, levels were between 13 and 14 g/dL. The median hemoglobin level
      triggering transfusion was 8.3 g/dL (5.2 mmol/L), irrespective of the malignant
      disease. CONCLUSION: Current use of ESAs for the treatment of cancer-associated
      anemia in Germany appears to be in good compliance with treatment guidelines.
      Similar results obtained from other studies in Europe and the US indicate this to
      be true beyond Germany.

PMID- 18715529
TI  - Tim Russert and sudden cardiac death after myocardial infarction.

PMID- 18715530
TI  - Dronedarone's effects on atrial fibrillation.

PMID- 18715531
TI  - Selective site pacing: rationale and practical application.
AB  - Although it has become traditional to place permanent pacemaker leads at the
      right ventricular apex and right atrial appendage, pacing from these locations
      poorly mimics normal physiology. A growing evidence base shows that right
      ventricular apical pacing results in ventricular dyssynchrony and various adverse
      effects. Provocative data from early trials suggest that pacing from alternate
      sites in the right ventricle--His bundle pacing, para-Hisian pacing, septal right
      ventricular outflow tract pacing, and right ventricular midseptal pacing--may
      lead to improved results. Similarly, early data suggest that right atrial pacing
      near Bachmann's bundle may lead to superior outcomes when compared with pacing
      from the right atrial appendage. Several large-scale, randomized clinical trials
      are now under way to establish the future role of selective site pacing.

PMID- 18715532
TI  - Ablation of atrial fibrillation: patient selection, technique, and outcome.
AB  - Ablation of atrial fibrillation (AF) has expanded from its limited application
      for patients with paroxysmal AF and structurally normal hearts to patients with
      persistent arrhythmia and more extensive structural heart disease. The
      cornerstone of this procedure involves pulmonary vein (PV) isolation, which is
      achieved by encircling lesions around the PVs. Success rates are highest for
      patients with paroxysmal AF, but modification of the technique to include linear
      lesions in the left atrium and targeting complex electrograms has improved
      outcomes in patients with long-lasting AF. The procedure remains complex, and the
      risk of complications must be balanced against the perceived benefit of
      maintaining sinus rhythm. For this reason, AF ablation is indicated in
      symptomatic patients who have failed at least one antiarrhythmic drug. Current
      studies will address catheter ablation's role as first-line therapy for patients
      with AF.

PMID- 18715533
TI  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia: an update.
AB  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic
      cardiomyopathy characterized by ventricular arrhythmias and structural
      abnormalities of the right ventricle (RV). The diagnosis is based on the
      International Task Force criteria. Cardiologists may not be aware of these
      diagnostic criteria for ARVC/D and may place too much importance on the results
      of MRI imaging of the right ventricle. Patients with ARVC/D usually have an
      abnormal 12-lead electrocardiogram, abnormal echocardiogram, and ventricular
      arrhythmias with a left bundle branch block morphology. If noninvasive testing
      suggests ARVC/D, invasive testing with an RV angiogram, RV biopsy, and
      electrophysiologic study is recommended. Once a diagnosis of ARVC/D is
      established, the main treatment decision involves whether to implant an
      implantable cardioverter-defibrillator. We also recommend treatment with beta
      blockers. Patients with ARVC/D are encouraged to avoid competitive athletics.
      Recent advances in the understanding of the genetic basis of ARVC/D have revealed
      that ARVC/D is a disease of desmosomal dysfunction.

PMID- 18715534
TI  - Brugada syndrome: recent advances and controversies.
AB  - The Brugada syndrome, first described as a new clinical entity in 1992, is widely
      recognized today as a form of inherited sudden cardiac arrest. The past 16 years
      witnessed a progressive increase in the number of reported cases and a dramatic
      proliferation of articles serving to define the clinical, genetic, cellular,
      ionic, and molecular aspects of the disease. This article provides a brief
      overview of recent advances in our understanding of the clinical presentation and
      molecular and cellular mechanisms and an update of existing controversies.

PMID- 18715535
TI  - Current concepts in the evaluation and management of syncope.
AB  - Syncope is a very common presentation with a wide differential diagnosis and
      equally wide prognostic implications. Recent work has highlighted the importance
      of an accurate history and physical examination as the basis of diagnosis,
      prognosis, and treatment. Several centers have evaluated the role of structured
      histories and comprehensive syncope evaluation guidelines and units in managing
      syncope. Although these do provide comprehensive care, whether they improve
      overall outcome and reduce costs is far from clear. This is partly because there
      are few effective treatments for the major cause of fainting, vasovagal syncope.
      Recent randomized trials have highlighted the roles of physical counterpressure
      maneuvers and midodrine and the limitations of treatment with beta blockers and
      permanent cardiac pacing.

PMID- 18715536
TI  - Putting the benefits of percutaneous coronary revascularization into perspective:
      from trials to guidelines.
AB  - Prompt delivery of percutaneous coronary revascularization in the acute setting
      has been shown to decrease mortality, length of hospitalization, and patient
      recovery time. However, its routine use in stable coronary disease is less
      validated, especially in the absence of adequate medical treatment. Several
      studies have looked into the benefits of percutaneous coronary revascularization.
      Based on these studies, many clinical guidelines have been developed to aid in
      decision making. In this article, we outline the benefits and reality of
      percutaneous coronary revascularization. We explore the major trials and use the
      latest clinical guidelines as a framework for our discussion on the applicability
      of this procedure in the setting of acute coronary syndromes and stable coronary
      disease.

PMID- 18715537
TI  - The risks and benefits of drug-eluting stents in the setting of STEMI.
AB  - Primary percutaneous coronary intervention (PCI) represents the treatment of
      choice in patients with ST-segment elevation myocardial infarction (STEMI). In
      randomized trials excluding STEMI patients, using drug-eluting stents (DES)
      significantly reduced angiographic restenosis and target vessel revascularization
      compared with bare metal stents (BMS); however, concerns exist regarding an
      increased follow-up incidence of stent thrombosis after DES implantation. This
      complication, which is associated with higher mortality and morbidity rates, may
      be more frequent among STEMI patients receiving DES versus BMS. Various
      registries, randomized trials, and two recent meta-analyses on patients
      undergoing primary PCI have shown that using DES is safe and is associated with
      significantly reduced rates of restenosis and repeat intervention without an
      increased risk of myocardial infarction or stent thrombosis at intermediate-term
      follow-up. However, large trials with hard clinical end points and longer follow
      up are needed before routine DES use can be recommended in patients undergoing
      primary PCI.

PMID- 18715538
TI  - Percutaneous coronary intervention without onsite surgical backup.
AB  - Although accepted in several countries abroad, the performance of percutaneous
      coronary intervention (PCI) without onsite surgical backup is controversial in
      the United States. Current guidelines from the United States do not endorse
      elective PCI in facilities without onsite surgical backup but acknowledge that
      primary PCI for ST-segment elevation myocardial infarction is acceptable under
      carefully regulated and monitored circumstances. This differs from guidelines
      developed by organizations in other countries. In the United States, data
      indicate that primary alone or primary and elective PCI without onsite surgery is
      currently being performed in all but seven states, and the number of patients
      treated in this setting is increasing. More than 40 articles reporting the
      outcomes and safety of PCI without onsite surgical backup have been published,
      but these are from a limited number of centers and are retrospective reviews or
      prospective registries, which have inherent limitations. Additional studies are
      currently under way to evaluate PCI's safety and effectiveness in this setting.

PMID- 18715539
TI  - Reperfusion options in ST-elevation myocardial infarction patients with expected
      delays.
AB  - Primary percutaneous coronary intervention (PPCI) is the optimal reperfusion
      strategy for ST-elevation myocardial infarction (STEMI) patients when performed
      in a timely manner by experienced providers. Unfortunately, only 25% of US
      hospitals have percutaneous coronary intervention (PCI) capability. Transfer for
      PPCI has also been shown to improve outcomes if transfer times are short and PCI
      can be performed within 90 minutes. However, many STEMI patients cannot be
      transferred in a timely fashion because of long distances, adverse weather, or
      process-of-care delays. Recent data support strategies that combine fibrinolysis
      with transfer for PCI under these circumstances. The critical issue that is still
      debated is the timing of PCI (immediate vs delayed vs rescue). The significance
      of time to reperfusion to mortality is important but less critical for PCI than
      for fibrinolysis, but time still matters. To optimize time to reperfusion for
      STEMI patients, all hospitals need to have predetermined protocols in place based
      on hospital characteristics and proximity to a catheterization laboratory.

PMID- 18715540
TI  - GP IIb/IIIa inhibitors during primary percutaneous coronary intervention for
      STEMI: new trial and registry data.
AB  - Primary percutaneous coronary intervention (PCI) with adjunctive glycoprotein
      (GP) IIb/IIIa receptor inhibitor therapy administered in the cardiac
      catheterization laboratory is the optimal reperfusion strategy for patients with
      ST-elevation myocardial infarction. Most available data regarding these agents
      are from trials comparing abciximab to placebo alone. Noninferiority trials
      comparing small-molecule GP IIb/IIIa receptor inhibitors, such as tirofiban and
      eptifibatide with abciximab, have used markers for myocardial reperfusion as
      primary end points but are underpowered to detect significant differences in hard
      clinical outcomes. Such a trial would need to enroll a very large number of
      patients and thus make it practically impossible to perform. Registry data reveal
      that most patients undergoing primary PCI are treated with small-molecule GP
      IIb/IIIa receptor inhibitors in clinical practice, and no observed difference is
      observed in safety and efficacy when compared with patients treated with
      abciximab therapy.

PMID- 18715541
TI  - Proteomic approach to identify candidate effector molecules during the in vitro
      immune exclusion of infective Teladorsagia circumcincta in the abomasum of sheep.
AB  - In the present study we have employed an in vitro organ challenge model to study
      the post-challenge responses in parasite naive and immune gastric tissue of
      sheep, in an attempt to identify the host derived factors involved in immune
      exclusion of Teladorsagia circumcincta larvae. Proteins present in the epithelial
      cells and mucus from ovine abomasa following parasite challenge in previously
      naive and immune animals were analysed through Matrix Assisted Laser
      Desorption/Ionization-Time of Flight (MALDI-Tof)-MS and shotgun proteomics. MALDI
      ToF analysis of epithelial cell lysates revealed that a number of proteins
      identified were differentially expressed in naive and immune cells. These
      included intelectin and lysozymes, which were present at higher levels in
      epithelial cell lysates derived from immune samples. A large number of proteins
      were identified in the mucosal wash from immune tissue which were not present in
      the mucosal wash of the naive tissue. Some of these proteins were present in
      washes of immune tissue prior to the parasite challenge including immunoglobulin
      A, galectin 14 and 15 and sheep mast cell protease 1. However, other proteins,
      such as calcium activated chloride channel and intelectin were only detected in
      the washings from the challenged tissue. The latter may be related to an enhanced
      mucus release, which may result in entrapment of infective larvae and thus
      reduced establishment in tissue that has been previously challenged with the
      parasite. In conclusion, several proteins have been identified which may be
      involved, either directly or indirectly, in the exclusion and immune elimination
      of incoming infective larvae. In the present study, the usefulness of the in
      vitro model has been confirmed, and the global proteomic approach has identified
      proteins that had not previously been associated with parasite exclusion from
      abomasal mucosa, such as the calcium activated chloride channel.

PMID- 18715542
TI  - Real-time monitoring of the cell agglutination process with a quartz crystal
      microbalance.
AB  - The real-time monitoring of the agglutination process of human hepatic normal
      cells (L-02) at the quartz crystal microbalance (QCM) gold (Au) electrode was
      performed. Two lectins, concanavalin A (Con A) and wheat germ agglutinin (WGA),
      induced the cell agglutination, resulting in the different Deltaf(0) and
      DeltaR(1) responses from those caused by the normal cell attachment and growth.
      The cell-Con A-cell aggregates had higher affinity for the Au substrate due to
      the excellent adsorption ability of Con A, which was revealed by increased
      Deltaf(0) and DeltaR(1) shifts and the obvious mass effect of QCM. In contrast,
      the lower adsorption ability of cell-WGA-cell aggregates was related to the same
      characteristic of WGA, presenting the decreased Deltaf(0) and DeltaR(1) responses
      and the time-extended adhesion phase. Parallel microscopic observation
      experiments were also carried out and exhibited comparable results. The Deltaf(0)
      responses during the processes of cell growth and cell agglutination were
      analyzed using the equations Deltaf(0)=alpha(0)+alpha(1)e(-t/tau(1))+alpha(2)e(
      t/tau(2))+alpha(3)e(-t/tau(3)) and Deltaf(0)=alpha(0)+alpha(1)e(
      t/tau(1))+alpha(2)e(-t/tau(2)), respectively. Furthermore, the current work
      proved that the QCM measurement technique based on cell agglutination was useful
      for discriminating hepatic normal cells (L-02) and hepatic cancer cells
      (Bel7402).

PMID- 18715543
TI  - Telmisartan prevented cognitive decline partly due to PPAR-gamma activation.
AB  - Telmisartan is a unique angiotensin receptor blocker (ARB) and partial agonist of
      peroxisome proliferator-activated receptor (PPAR)-gamma. Here, we investigated
      the preventive effect of telmisartan on cognitive decline in Alzheimer disease.
      In ddY mice, intracerebroventricular injection of Abeta 1-40 significantly
      attenuated their cognitive function evaluated by shuttle avoidance test.
      Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited
      such cognitive decline. Interestingly, co-treatment with GW9662, a PPAR-gamma
      antagonist, partially inhibited this improvement of cognitive decline. Another
      ARB, losartan, which has less PPAR-gamma agonistic effect, also inhibited Abeta
      injection-induced cognitive decline; however the effect was smaller than that of
      telmisartan and was not affected by GW9662. Immunohistochemical staining for
      Abeta showed the reduced Abeta deposition in telmisartan-treated mice. However,
      this reduction was not observed in mice co-administered GW9662. These findings
      suggest that ARB has a preventive effect on cognitive impairment in Alzheimer
      disease, and telmisartan, with PPAR-gamma activation, could exert a stronger
      effect.

PMID- 18715544
TI  - Generalized aphid population growth models with immigration and cumulative-size
      dependent dynamics.
AB  - Mechanistic models in which the per-capita death rate of a population is
      proportional to cumulative past size have been shown to describe adequately the
      population size curves for a number of aphid species. Such previous cumulative
      sized based models have not included immigration. The inclusion of immigration is
      suggested biologically as local aphid populations are initiated by migration of
      winged aphids and as reproduction is temperature-dependent. This paper
      investigates two models with constant immigration, one with continuous
      immigration and the other with restricted immigration. Cases of the latter are
      relatively simple to fit to data. The results from these two immigration models
      are compared for data sets on the mustard aphid in India.

PMID- 18715545
TI  - Performing IgE serum testing due to bioinformatics matches in the allergenicity
      assessment of GM crops.
AB  - Proteins introduced into genetically modified (GM) organisms through genetic
      engineering must be evaluated for their potential to cause allergic disease under
      various national laws and regulations. The Codex Alimentarius Commission guidance
      document (2003) calls for testing of serum IgE binding to the introduced protein
      if the gene was from an allergenic source, or the sequence of the transferred
      protein has >35% identity in any segment of 80 or more amino acids to a known
      allergen or shares significant short amino acid identities. The Codex guidance
      recognized that the assessment will evolve based on new scientific knowledge.
      Arguably, the current criteria are too conservative as discussed in this paper
      and they do not provide practical guidance on serum testing. The goals of this
      paper are: (1) to summarize evidence supporting the level of identity that
      indicates potential risk of cross-reactivity for those with existing allergies;
      (2) to provide example bioinformatics results and discuss their interpretation
      using published examples of proteins expressed in transgenic crops; and (3) to
      discuss key factors of experimental design and methodology for serum IgE tests to
      minimize the rate of false negative and false positive identification of
      potential allergens and cross-reactive proteins.

PMID- 18715546
TI  - Flavonoid glycosides isolated from Salicornia herbacea inhibit matrix
      metalloproteinase in HT1080 cells.
AB  - Flavonoid glycosides, isorhamnetin 3-capital O, Cyrillic-beta-d-glucoside, and
      quercetin 3-O-beta-d-glucoside were isolated from Salicornia herbacea and their
      inhibitory effects on matrix metalloproteinase-9 and -2 (MMP-9 and -2) were
      evaluated in human fibrosarcoma cell line (HT1080). In zymography experiments,
      these flavonoid glycosides led to the reduction of the expression levels and
      activities of MMP-9 and -2 without any significant difference between these
      flavonoid glycosides. Protein expression levels of both MMP-9 and MMP-2 were
      inhibited and TIMP-1 (tissue inhibitor of metalloproteinase-1) protein level was
      enhanced by these flavonoid glycosides. Moreover, a transfection study carried
      out with AP-1 reporter construct revealed that the reporter activity was
      suppressed by treatment with isorhamnetin 3-capital O, Cyrillic-beta-d-glucoside.
      Therefore, these results suggested that these flavonoid glycosides have a
      potential as valuable natural chemopreventive agents for cancer.

PMID- 18715547
TI  - Methyl tert-butyl ether (MTBE) induced Ca(2+)-dependent cytotoxicity in isolated
      rabbit tracheal epithelial cells.
AB  - As a volatile synthetic organic chemical, methyl tert-butyl ether (MTBE) was the
      most common gasoline additive. The increasing use of MTBE raised concern over its
      health safety. Inhalation was the principle route of exposure for the general
      population. This study used a model of rabbit tracheal epithelial cells (RTEs) in
      primary culture to investigate the cytotoxic effects induced by MTBE and the
      potential mechanism. RTEs were incubated with medium alone (control), 0.5, 50,
      5000ppm MTBE respectively. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo
      liumbromide) assay, staining with fluorescein diacetate, propidium iodide and
      lactate dehydrogenase leakage ratio were used to assess MTBE cytotoxicity on
      cells. We also observed a significant elevation in cytosolic Ca2+ by fluorescence
      probe Fluo-3AM at 3, 6 and 12h following exposure to MTBE. Loss of mitochondrial
      membrane potential (MMP) was detected following 12 and 24h treatment of NP and
      assessment by rhodamine 123 (Rh123) staining. Activity changes of the Ca(2+)
      ATPase, Ca(2+)-Mg(2+)-ATPase following MTBE treatment displayed a similar trend,
      suggesting an initial elevation before 6h and subsequent dramatic decrease at
      12h. Our results demonstrated that induction of cell injury, associated with
      mitochondrial dysfunction, and alterations in cytosolic Ca2+ in RTEs represent
      key mechanisms by which MTBE exerts its cytotoxic effects.

PMID- 18715548
TI  - Pharmacokinetics of meloxicam administered as regular and fast dissolving
      formulations to the rat: influence of gastrointestinal dysfunction on the
      relative bioavailability of two formulations.
AB  - It is believed that acute pain suppresses nervus vagus, thereby, influencing
      gastrointestinal secretion and motility, which are the two factors that are
      necessary for disintegration and dissolution of solid dosage forms. We studied
      the pharmacokinetics of meloxicam and the effect of vagal suppression on the oral
      bioavailability and bioequivalence using a marketed (Brand) and a fast dissolving
      (FD) formulation. In simulated gastric juice, FD was disintegrated in 30s and
      released 30% of its meloxicam in 15 min and 60% in 2h. Brand was disintegrated in
      4.5 min with a dissolution rate of 5.6% in 30 min that stayed plateau for the 2h
      experiment time. To suppress the vagus nerve, intraperitoneal injection of
      20mg/kg propantheline 1 and 2h before meloxicam administration was used.
      Meloxicam (0.9 mg/kg) was administered to both control and vagally suppressed
      rats i.v. (n=4-6/group) as well as orally in a paired random fashion as broken
      pieces of Brand or FD tablets (n=7/ group). Serial (0-48h) blood samples were
      collected for pharmacokinetic and bioavailability studies. Relative
      bioavailability was measured according to a method in use for bioequivalence
      assessments. Systemic pharmacokinetics of meloxicam was not affected by vagal
      suppression. Absolute bioavailability of meloxicam, based on 0-48h measurement,
      was >0.68 regardless of the type of formulation and treatment. Vagal suppression,
      however, significantly reduced AUC(0-24) (microg h mL(-1)) for Brand (control,
      58.8+/-22.0 vs treated, 22.1+/-9.7) but not for FD (control, 63.5+/-17.9 vs
      treated, 64.6+/-8.9) indicating a reduced absorption rate for the former. The
      peak time for Brand was also significantly delayed by over 20h for Brand and not
      for FD. Relative bioavailability was confirmed between FD and Brand that were in
      control but not in the vagally suppressed rats, indicating a disease-dependent
      bioequivalence. The effect of vagal suppression on the drug absorption rate can
      be obviated if the disintegration and dissolution become independent of
      gastrointestinal motility and secretion.

PMID- 18715549
TI  - Solid form screening--a review.
AB  - Solid form screening, the activity of generating and analysing different solid
      forms of an active pharmaceutical ingredient (API), has become an essential part
      of drug development. The multi-step screening process needs to be designed,
      performed and evaluated carefully, since the decisions made based on the
      screening may have consequences on the whole lifecycle of a pharmaceutical
      product. The selection of the form for development is made after solid form
      screening. The selection criteria include not only pharmaceutically relevant
      properties, such as therapeutic efficacy and processing characteristics, but also
      intellectual property (IP) issues. In this paper, basic principles of solid form
      screening are reviewed, including the methods used in experimental screening
      (generation, characterisation and analysis of solid forms, data mining tools, and
      high-throughput screening technologies) as well as basics of computational
      methods. Differences between solid form screening strategies of branded and
      generic pharmaceutical manufacturers are also discussed.

PMID- 18715550
TI  - The base rate of Wada test failure.
AB  - Although functional brain imaging can lateralize language functioning and has the
      potential to assess the functional integrity of the mesial temporal lobe memory
      structures, imaging protocols are not currently available for clinical use.
      Assessing the risk of post-epilepsy surgery memory decline is an important part
      of treatment planning, and the Wada test remains the current technique. The Wada
      test is invasive and has limitations with respect to sensitivity and specificity.
      We describe an audit of 141 consecutive Wada test results looking at the base
      rate of failure and clinical characteristics of failure. The objective was to
      provide base rate data that support decision making regarding selective use of
      the Wada test. We conclude that right-handed patients with right temporal lesions
      who have strong verbal memory are very unlikely to fail and probably do not need
      to undergo the Wada test. Patients with left temporal lesions are more likely to
      fail regardless of handedness and regardless of baseline neuropsychological test
      data. We propose that until functional imaging protocols become available to
      supersede the Wada test, patients should be considered for the Wada test on a
      case-by-case basis.

PMID- 18715551
TI  - Genetic and environmental influences on human dental variation: a critical
      evaluation of studies involving twins.
AB  - Utilising data derived from twins and their families, different approaches can be
      applied to study genetic and environmental influences on human dental variation.
      The different methods have advantages and limitations and special features of the
      twinning process are important to consider. Model-fitting approaches have shown
      that different combinations of additive genetic variance (A), non-additive
      genetic variance (D), common environmental variance (C), and unique environmental
      variance (E) contribute to phenotypic variation within the dentition, reflecting
      different ontogenetic and phylogenetic influences. Epigenetic factors are also
      proposed as important in explaining differences in the dentitions of monozygotic
      co-twins. Heritability estimates are high for most tooth size variables, for
      Carabelli trait and for dental arch dimensions, moderate for intercuspal
      distances, and low for some occlusal traits. In addition to estimating the
      contributions of unmeasured genetic and environmental influences to phenotypic
      variation, structural equation models can also be used to test the effects of
      measured genetic and environmental factors. Whole-genome linkage analysis,
      association analysis of putative candidate genes, and whole genome association
      approaches, now offer exciting opportunities to locate key genes involved in
      human dental development.

PMID- 18715552
TI  - First record of L-quebrachitol in Allophylus edulis (Sapindaceae).
AB  - Allophylus edulis, commonly called 'Chal chal', is a member of the Sapindaceae
      occurring in the Uruguayan and Brazilian native flora. During the phytochemical
      analysis of two Chal chal specimens from two well-differentiated geographical
      zones (Assis, Sao Paulo, Brazil, and Santa Lucia, Canelones, Uruguay),
      considerable amounts of L-quebrachitol were isolated from both samples. The
      isolation was carried out from the ethanolic twig extracts obtained by maceration
      of both vegetal samples. White easily distinguishable crystals were mechanically
      separated, washed, and characterized by 1D and 2D NMR experiments and by MS data.
      Such techniques confirmed that the crystals isolated from sources collected in
      both countries resulted in the same compound, l-quebrachitol, a natural product
      not previously reported for this species and one that has been investigated as a
      sugar substitute for diabetics. Worthy of note, the content of L-quebrachitol in
      A. edulis may be the chemical basis to explain its ethnobotanical uses, since
      infusions of this plant are used to treat diabetes in the practice of local
      traditional medicine.

PMID- 18715553
TI  - Mycobacterial HSP70 as an adjuvant in the design of an idiotype vaccine against a
      murine lymphoma.
AB  - Mycobacterial HSP70 protein coupled with ovalbumin is known to elicit antigen
      specific CD8(+) T-cell response. We investigated whether anti-idiotype immunity
      can likewise be enhanced using a conjugate of recombinant mycHSP70 and the Ig Id
      in a murine lymphoma model, A20. Plasmids were constructed of A20 tumor to
      generate A20Id-HSP70 (scFv-H), unconjugated A20Id (scFv), and mycHSP70 (H)
      recombinant proteins. We evaluated their relative efficacy in activating anti
      tumor immunity that can reduce the mortality of tumor-challenged BALB/c mice;
      significantly, a longer term protection (>50% of the population) was observed in
      mice vaccinated with scFv-H compared to those receiving the scFv or H proteins.
      Concomitantly a much higher-level activation in anti-A20 cytotoxic T-cell
      activity, IFN-gamma secretion and predominantly anti-A20 IgG2a response was also
      observed with the scFv-H group. Thus, conjugating HSP70 with the A20Id renders
      the latter significantly immunogenic and affords longer protection against A20
      tumor progression.

PMID- 18715554
TI  - Motor cortical activity related to movement kinematics exhibits local spatial
      organization.
AB  - While it is generally accepted that multiple neurons cooperate to generate
      movement, the precise mechanisms are largely unknown. One way to generate a
      robust local control signal is for nearby neurons to share similar properties. To
      study this possibility, we recorded neural activity from the macaque motor cortex
      during two drawing tasks: free scribbling, and tracing given paths. We analyzed
      neural activity in relation to three kinematic parameters - position, velocity,
      and acceleration - while explicitly considering temporal correlations between
      them. Single-unit (SU) activity was typically related to one parameter, most
      often velocity, and tended to precede movement. Different SUs encoded different
      parameters, but nearby units tended to prefer the same parameter. Moreover, while
      SUs covered a wide range of positions, velocity directions, and acceleration
      directions, SUs recorded by the same electrode tended to prefer similar values of
      the same parameter. Nevertheless, some nearby units exhibited marked differences.
      Multi-unit activity (MUA), estimating the spiking activity of many neurons around
      the recording electrode, also tended to be related to one parameter and precede
      movement. However, overall correlations between MUA and movement were more than
      twice as strong as SU correlations. Finally, SUs and MUAs recorded by the same
      electrode tended to share similar properties. These two lines of evidence
      converge to suggest that activity of motor cortex neurons within approximately
      200 micrometers is accumulated in a manner useful for representing a single
      parameter. However, even within a small region there are also neurons related to
      other parameters, potentially facilitating coordination between distinct
      parameters.

PMID- 18715555
TI  - Drawing cartoon faces--a functional imaging study of the cognitive neuroscience
      of drawing.
AB  - We report a functional imaging study of drawing cartoon faces. Normal, untrained
      participants were scanned while viewing simple black and white cartoon line
      drawings of human faces, retaining them for a short memory interval, and then
      drawing them without vision of their hand or the paper. Specific encoding and
      retention of information about the faces were tested for by contrasting these two
      stages (with display of cartoon faces) against the exploration and retention of
      random dot stimuli. Drawing was contrasted between conditions in which only
      memory of a previously viewed face was available versus a condition in which both
      memory and simultaneous viewing of the cartoon were possible, and versus drawing
      of a new, previously unseen, face. We show that the encoding of cartoon faces
      powerfully activates the face-sensitive areas of the lateral occipital cortex and
      the fusiform gyrus, but there is no significant activation in these areas during
      the retention interval. Activity in both areas was also high when drawing the
      displayed cartoons. Drawing from memory activates areas in posterior parietal
      cortex and frontal areas. This activity is consistent with the encoding and
      retention of the spatial information about the face to be drawn as a visuo-motor
      action plan, either representing a series of targets for ocular fixation or as
      spatial targets for the drawing action.

PMID- 18715556
TI  - Maternal and infant urinary phthalate metabolite concentrations: are they
      related?
AB  - BACKGROUND: Phthalates are synthetic chemicals that are ubiquitous in our society
      and may have adverse health effects in humans. Detectable concentrations of
      phthalate metabolites have been found in adults and children, but no studies have
      examined the relationship between maternal and infant phthalate metabolite
      concentrations. OBJECTIVE: We investigated the relationship between maternal and
      infant urinary phthalate metabolite concentrations. METHODS: We measured nine
      phthalate metabolites in urine samples from 210 mother/infant pairs collected on
      the same study visit day (1999-2005) and obtained demographic history from
      questionnaires. Using multivariate linear regression analyses, we examined the
      degree to which maternal urine phthalate metabolite concentration predicted
      infant phthalate metabolite concentration. All analyses were adjusted for infant
      age, creatinine concentration, and race. RESULTS: Correlation coefficients
      between phthalate metabolite concentrations in the urine of mothers and their
      infants were generally low but increased with decreasing age of infant. In
      multivariate analyses, mother's phthalate metabolite concentrations were
      significantly associated with infants' concentrations for six phthalate
      metabolites: monobenzyl phthalate, monoethyl phthalate, monoisobutyl phthalate,
      and three metabolites of di(2-ethylhexyl) phthalate: mono(2-ethylhexyl)
      phthalate, mono(2-ethyl-5-hydroxy-hexyl) phthalate, and mono(2-ethyl-5-oxo-hexyl)
      phthalate (p-values for all coefficients <0.05). DISCUSSION: Mother's urine
      phthalate metabolite concentration is significantly associated with infant urine
      phthalate metabolite concentration for six phthalate metabolites. It is plausible
      that shared exposures to phthalates in the immediate surrounding environment
      accounted for these relationships, but other unidentified sources may also
      contribute to infants' phthalate exposures. This study indicates the importance
      of further identifying infant phthalate exposures that may be distinct from
      maternal exposures in order to decrease overall infant phthalate exposures.

PMID- 18715557
TI  - How interventional radiology changed the practice of a trauma surgeon.
AB  - Trauma Surgery, with the assistance of advanced technology especially in Imaging
      (formerly Radiology), enables it to have patient management approaching John
      Hunter's ideal of treatment by stratagem rather than the "force" of an open
      operation.

PMID- 18715558
TI  - Siatic nerve regeneration in rats stimulated by fibrin glue containing nerve
      growth factor: an experimental study.
AB  - OBJECTIVE: To study the effects of fibrin sealant containing nerve growth factor
      on the peripheral nerve regeneration. STUDY DESIGN: A four-group experimental
      design with repeated measures on one factor was used. METHODS: Fibrin glue (FG)
      containing NGF was injected into the site of end-and-end sutured peripheral nerve
      (sciatic nerve) (group I: NGF+FG), meanwhile three control groups were set-up:
      group II (NGF), group III (FG), and group IV (normal saline). Observation to the
      function and morphology of the sciatic nerve was carried out at the end of 4, 8,
      12 weeks postoperation. Data were analyzed using ANOVA, with the appropriate post
      hoc between-groups comparison test. RESULTS: Electrophysiological testing. The
      NAP and NCV of group I (NGF+FG) were greater than those of group II (NGF), group
      III (FG), or group IV (normal saline) (p<0.05). Sciatic functional index (SFI).
      It began to ameliorate at 4 weeks postoperation and SFI increased as time went
      on. And the SFI in group I (NGF+FG) was better than those in group II (NGF),
      group III (FG), or group IV (normal saline) (p<0.05). Morphology. In the MGF
      stained sections, dissociated myelin debris was less and regenerated nerve fibres
      were in larger quantities in group I (NGF+FG) than in other groups. In the HE
      stained sections, regenerated nerve fibres distal to anastomosis significantly
      increased, and axon and myelin had a clearer outline in group I (NGF+FG) than in
      other groups. Electron microscopy indicated that the regenerated nerve fibres
      were more mature and the development of the axons was greater in group I than in
      other control groups. CONCLUSIONS: FG can be used as carrier of exogenous NGF,
      and they can provide synergistic effects for the peripheral nerve regeneration
      after the integration of the two.

PMID- 18715559
TI  - Abdomen--interventions for solid organ injury.

PMID- 18715560
TI  - Replantation of articular composite tissue masses severed from extremities.
AB  - SUMMARY: The techniques and outcomes of in situ replantation are discussed for
      managing 5 cases of articular composite tissue masses severed from an extremity
      (digit). All 5 cases treated with in situ replantation survived. Rehabilitation
      was performed after surgery. Follow-ups of 2-5 years showed good appearance,
      satisfactory functional and sensory recovery. In situ replantation is indicated
      for an articular composite tissue masses severed from an extremity (digit), if
      its structure is complete and a blood supply vessel in the mass is available for
      anastomosis. Replantation can achieve better outcomes than transfer or grafting
      of adjacent skin or osteocutaneous flaps, or transplantation of a
      metatarsophalangeal or interphalangeal joint.

PMID- 18715561
TI  - Current treatment concepts for neuromas-in-continuity.
AB  - SUMMARY: A neuroma-in-continuity is a neuroma that results from failure of the
      regenerating nerve growth cone to reach peripheral targets. It occurs within an
      intact nerve in response to internally damaged fascicles, resulting in a distal
      portion of the nerve that no longer functions properly. Management of neuromas-in
      continuity is challenging. Chemical methods, and microsurgical techniques
      including fascicular ligation, and burying into muscle and bone have been
      reported to prevent neuroma-in-continuity formation. The purpose of this article
      is to present novel techniques for neuroma-in-continuity management, and to
      discuss the related literature.

PMID- 18715562
TI  - The "con" of concept analysis A discussion paper which explores and critiques the
      ontological focus, reliability and antecedents of concept analysis frameworks.
AB  - This paper draws on the work of Paley and Duncan et al in order to extend and
      engender debate regarding the use of Concept Analysis frameworks. Despite the
      apparent plethora of Concept Analysis frameworks used in nursing studies we found
      that over half of those used were derived from the work of one author. This paper
      explores the suitability and use of these frameworks and is set at a time when
      the numbers of published concept analysis papers are increasing. For the purpose
      of this study thirteen commonly used frameworks, identified from the nursing
      journals 1993 to 2005, were explored to reveal their origins, ontological and
      philosophical stance, and any common elements. The frameworks were critiqued and
      links made between their antecedents. It was noted if the articles contained
      discussion of any possible tensions between the ontological perspective of the
      framework used, the process of analysis, praxis and possible nursing theory
      developments. It was found that the thirteen identified frameworks are mainly
      based on hermeneutic propositions regarding understandings and are interpretive
      procedures founded on self-reflective modes of discovery. Six frameworks rely on
      or include the use of casuistry. Seven of the frameworks identified are
      predicated on, or adapt the work of Wilson, a school master writing for his
      pupils. Wilson's framework has a simplistic eleven step, binary and reductionist
      structure. Other frameworks identified include Morse et al's framework which this
      article suggests employs a contestable theory of concept maturity. Based on the
      findings revealed through our exploration of the use of concept analysis
      frameworks in the nursing literature, concerns were raised regarding the
      unjustified adaptation and alterations and the uncritical use of the frameworks.
      There is little evidence that these frameworks provide the necessary depth, rigor
      or replicability to enable the development in nursing theory which they underpin.

PMID- 18715563
TI  - Immuno-inflammatory and thrombotic/fibrinolytic variables associated with acute
      ischemic stroke diagnosis.
AB  - INTRODUCTION: Accumulating evidence suggests that inflammation plays an important
      role in the development of acute cerebrovascular disease. The aim of this study
      is to evaluate the predictive value of a series of candidate serum immuno
      inflammatory and thrombotic/fibrinolitic molecules towards diagnosis of acute
      ischemic stroke. MATERIALS AND METHODS: We enrolled 120 consecutive patients with
      a diagnosis of acute ischemic stroke and 123 consecutive hospitalized control
      patients without a diagnosis of acute ischemic stroke. We evaluated plasma levels
      of IL-1beta, TNF-beta, IL-6 and IL-10, E-selectin, P-selectin, sICAM-1 and sVCAM
      1 as markers of immuno-inflammatory activation, vWF plasma levels as a marker of
      endothelial dysfunction, TPA antigen and PAI-1 plasma levels as a marker of a
      prothrombotic state. RESULTS: TNF-alpha, PAI-1 and TPA on bivariate logistic
      regression were highly correlated to stroke diagnosis. Among the other variables
      maintained in the final model ILbeta, Selectin E, were significantly associated
      with acute ischemic stroke diagnosis, whereas IL-6, VICAM-1, ICAM-1 and
      neutrophil percentage showed only a slight or no association with stroke
      diagnosis. Furthermore, only the continuous values of TNF-alpha, PAI-1 and TPA
      showed a significant predictive value and likelihood ratio, with an area under
      the ROC curve of 98.6%, 97.1% and 99.9%, respectively. DISCUSSION: Our findings
      could suggest the high diagnostic power of these immuno-inflammatory and
      thrombotic/fibrinolytic variables in patients with acute ischemic stroke.
      Although our results are encouraging, additional studies are needed to establish
      the validity of this approach.

PMID- 18715564
TI  - Serum gamma-glutamyltransferase is not associated to peripheral arterial disease
      in type 2 diabetic patients: Cross-sectional findings.

PMID- 18715565
TI  - Variability of arterial wall shear stress, its dependence on vessel diameter and
      implications for Murray's Law.

PMID- 18715566
TI  - A proteomic approach to differentiate histologically classified stable and
      unstable plaques from human carotid arteries.
AB  - OBJECTIVES: By using proteomics we isolated and identified proteins that were
      expressed/retained in stable and unstable human carotid artery atherosclerotic
      plaques. METHODS: The criteria for plaque instability were the presence of a thin
      fibrous cap or fissured cap covering the foamy or necrotic core, and the presence
      of overt, hemorrhagic, ulcerated or thrombotic plaques. Proteins were extracted
      from finely minced endarterectomy specimens (19 stable and 29 unstable plaques)
      and separated by two-dimensional gel electrophoresis. Coomassie Blue-stained gels
      were analysed using PD-Quest software. RESULTS: A total of 57 distinct spots
      corresponding to 33 different proteins were identified by matrix assisted laser
      desorption/ionization mass spectrometry using the NCBI database. Most of the
      spots were present in both types of extracts, although significantly (p<0.05)
      differing in abundance between them. Compared to stable plaque, unstable ones
      showed reduced abundance of: protective enzymes SOD3 and GST, small heat shock
      proteins HSP27 and HSP20, annexin A10, and Rho GDI. In unstable plaques the more
      abundant proteins were: ferritin light subunit, SOD 2 and fibrinogen fragment D.
      For fibrinogen fragment D, the increased levels in unstable versus stable plaques
      was confirmed by Western blot analysis. CONCLUSIONS: Since many of the
      differentially expressed proteins are known to have a functional role in
      inflammation and oxidative stress, we speculate that they may be involved in
      events relating to plaque stability.

PMID- 18715567
TI  - The effect of axial load on the sagittal plane curvature of the upright human
      spine in vivo.
AB  - Determining the effect of load carriage on the human spine in vivo is important
      for determining spinal forces and establishing potential mechanisms of back
      injury. Previous studies have suggested that the natural curvature of the spine
      straightens under load, but are based on modelling and external measurements from
      the surface of the back. In the current study, an upright positional MRI scanner
      was used to acquire sagittal images of the lumbar and lower thoracic spine of 24
      subjects. The subjects were imaged in standing whilst supporting 0, 8 and 16 kg
      of load which was applied axially across the shoulders using an apron. An active
      shape model of the vertebral bodies from T10 to S1 was created and used to
      characterise the effect of load. The results from the shape model showed that the
      behaviour of the average-shaped spine was to straighten slightly. However, the
      shape model also showed that the effect of load exhibited systematic variation
      between individuals. Those who had a smaller than average curvature before
      loading straightened under load, whereas those who had a greater than average
      curvature before loading showed an increase in curvature under load. The
      variation in behaviour of differently shaped spines may have further implications
      for the effects of load in lifting manoeuvres and in understanding the aetiology
      of back pain.

PMID- 18715568
TI  - Screening of protein-ligand interactions using dynamic protein-affinity
      chromatography solid-phase extraction-liquid chromatography-mass spectrometry.
AB  - A novel methodology is shown enabling the screening of mixtures of compounds for
      their affinity to a receptor protein. The system presented, dynamic protein
      affinity chromatography solid-phase extraction (DPAC-SPE), overcomes the
      limitations of the existing methods by performing an incubation of the His-tagged
      protein with a mixture of possible ligands, which are still in their native
      conditions. This is followed by a fully automated affinity trapping step, coupled
      on-line to an LC-MS system in order to detect and identify the bound ligands. The
      system has been optimized using a commercially available on-line SPE system,
      using the estrogen receptor alpha (ERalpha) as model protein. A representative
      range of ligands with sub-nanomolar to millimolar affinities has been identified
      successfully from a mixture. The weakest binder that can be identified is
      norethindrone (approximately K(d)=0.1-1mM). The same setup also provides the
      possibilities to measure EC50 curves of both weak and strong binders.

PMID- 18715569
TI  - The effect of the model's presence and of negative evidence on infants' selective
      imitation.
AB  - This study demonstrated selective "rational" imitation in infants in two testing
      conditions: in the presence or absence of the model during the response phase. In
      the study, 14-month-olds were more likely to imitate a tool-use behavior when a
      prior failed attempt emphasized the logical reason and relevance of introducing
      this novel means, making it cognitively transparent for the infants. Infants also
      learned imitatively from the cognitively opaque (yet socially communicated)
      modeling situation, but to a lesser degree. Furthermore, the presence of the
      model as a social partner during testing influenced the performance of infants in
      that they were more likely to imitate the novel means when the model was present
      during testing. These results highlight the important interaction of interpretive
      schemas (e.g., causality, teleological stance) and social communicative cues in
      action interpretation guiding imitative learning.

PMID- 18715570
TI  - Serotonin receptor HTR1A and HTR2C variants and personality traits in suicide
      attempters and controls.
AB  - INTRODUCTION: Serotonin has been extensively studied in relation to both
      personality features and suicidal behaviours. OBJECTIVE: In this study, we
      considered the association between the serotonin receptor 1A (HTR1A) and 2C
      (HTR2C) SNPs and personality traits, as measured by the Temperament and Character
      Inventory (TCI), in a sample of suicide patients and healthy volunteers. METHODS:
      The SNPs considered were, for HTR1A rs1423691, rs878567 and rs6295, and for HTR2C
      rs547536, rs2192372, rs6318, rs2428707, rs4272555 and rs1801412. The sample was
      composed of three groups: two German samples, consisting of a healthy control
      group of 289 subjects (42.6% males, mean age: 45.2+/-14.9) and a psychiatric
      patient group of 111 suicide attempters (38.7% males, mean age: 39.2+/-13.6), and
      an Italian sample, composed of 64 mood disorder patients (35.9% males, mean age:
      43.0+/-14.8). In the German samples all the SNPs were investigated, while in the
      Italian sample only the HTR1A rs6295 and the HTR2C rs6318 SNPs were considered.
      RESULTS: Controlling for sex, age and educational level, single markers and
      haplotypes were not or only marginally associated with personality dimensions.
      CONCLUSIONS: Our study does not support the role of HTR1A and HTR2C gene variants
      on personality traits in both healthy volunteers and mood disorder patients.

PMID- 18715571
TI  - Compartmentalization of inflammation in the CNS: a major mechanism driving
      progressive multiple sclerosis.
AB  - In multiple sclerosis (MS) the CNS is not only the target of the pathological
      immune response, but the CNS itself becomes an immunological compartment during
      the course of the disease. This comprises (i) inflammation beyond classical white
      matter lesions, (ii) intrathecal Ig production with oligoclonal bands, (iii) an
      environment fostering immune cell persistence, (iv) follicle-like aggregates in
      the meninges, (v) a disruption of the blood-brain barrier also outside of active
      lesions, which allows influx of autoantibodies possibly promoting demyelination
      or axonal injury and influx of fibrinogen driving inflammation.

PMID- 18715573
TI  - Ultrasound fails to delineate significant renal pathology in children with
      urinary tract infections: a case for dimercapto-succinic acid scintigraphy.
AB  - PURPOSE: Routine radiological evaluation in children with urinary tract
      infections includes ultrasound. Additional dimercapto-succinic acid scintigraphy
      in this setting is a common but not routine practice to determine whether there
      is parenchymal injury. Because dimercapto-succinic acid scintigraphy involves
      further time, expense and radiation, we determined whether ultrasound findings
      could substitute for dimercapto-succinic acid scintigraphy. Therefore, in
      children with urinary tract infections we researched the incidence of discordant
      findings between dimercapto-succinic acid scintigraphy and normal ultrasound.
      MATERIALS AND METHODS: A retrospective review of children with a history of
      urinary tract infections who had normal ultrasound and dimercapto-succinic acid
      scintigraphy within 6 weeks of each other was performed through a chart review.
      Children with pyelonephritis within 4 months of the radiological tests were
      excluded. Dimercapto-succinic acid scintigraphy was considered abnormal if there
      was less than 40% differential function, global atrophy or focal defects.
      RESULTS: From January 2005 to December 2006, 100 children met inclusion criteria.
      Median patient age was 4.5 years (range 4 months to 19 years) and 84% were
      female. Of the 100 children 74 (74%) demonstrated vesicoureteral reflux and 18
      (18%) showed abnormal dimercapto-succinic acid scintigraphy despite normal
      ultrasound. Children with vesicoureteral reflux showed an increased incidence of
      abnormal dimercapto-succinic acid scintigraphy compared to those without
      vesicoureteral reflux (20.3% vs 11.5%), although this did not attain statistical
      significance (p = 0.04). CONCLUSIONS: Although dimercapto-succinic acid
      scintigraphy is not part of routine practice in all children with urinary tract
      infections and/or vesicoureteral reflux, it is frequently abnormal despite normal
      ultrasound. Therefore, dimercapto-succinic acid scintigraphy should be considered
      in these patients to evaluate cortical defects and possibly guide further
      management.

PMID- 18715576
TI  - Prospective followup in patients after complete primary repair of bladder
      exstrophy.
AB  - PURPOSE: The new technique of complete primary repair of bladder exstrophy has
      offered the promise of improved bladder functional outcomes and yet longitudinal
      followup in patients with exstrophy who have undergone this form of closure is
      sparse. We present our median 5-year data on patients who have undergone complete
      primary repair of bladder exstrophy. MATERIALS AND METHODS: The records of
      patients who underwent complete primary repair of bladder exstrophy were analyzed
      retrospectively. Patients were followed prospectively using case report forms,
      radiological and clinical data, and semistructured parental and patient
      interviews. We reviewed parameters including clinical events, scarring on renal
      scan, vesicoureteral reflux, surgical procedures, urodynamic studies, urinary and
      fecal continence status, and episodes of urinary tract infection. RESULTS: From
      1994 to 2007 complete primary repair of bladder exstrophy was performed in 32
      patients. Of these patients 28 underwent closure within 72 hours of life,
      including 20 males and 8 females, and 4 underwent it after 72 hours at ages 7
      days to 12 months. One patient underwent complete primary repair of bladder
      exstrophy elsewhere. Median followup was 5 years (range 1 to 13). In 32 patients
      a total of 193 surgical procedures were done, of which 40% were minor endoscopic
      cases. Six of 23 males (26%) underwent bladder neck reconstruction at a median
      age of 4.5 years (range 4 to 10). Two boys and 1 girl received Deflux injection
      to the bladder neck at ages 3 to 5 years. To date no patient has undergone
      bladder augmentation. Nine patients (28%) had 1 to 4 episodes of pyelonephritis
      and 6 had cortical defects on renal scan. A total of 30 patients were voiding or
      incontinent via the urethra. One patient performed clean intermittent
      catheterization via the urethra and 1 performed it via appendicovesicostomy. All
      4 children who were at least 6 months from bladder neck reconstruction after
      complete primary repair of bladder exstrophy had urinary continence periods of 2
      to 3 hours or greater. Parents did not report any fecal incontinence or soiling
      in children older than 4 years. Relative to males the females had better urinary
      continence and a decreased need for bladder neck reconstruction. CONCLUSIONS:
      Complete primary repair of bladder exstrophy has been shown to be safe and
      efficacious. Prospective followup in this small number of evaluable patients
      reveals that continence periods of more than 2 hours are possible in patients
      after bladder neck reconstruction. Long-term followup in patients after complete
      primary repair of bladder exstrophy continues to be necessary to establish the
      long-term effects of this procedure.

PMID- 18715581
TI  - Complete androgen insensitivity: the role of the surgeon.
AB  - PURPOSE: This is a retrospective series of the surgical management of complete
      androgen insensitivity at a single institution. MATERIALS AND METHODS: The
      records of 16 patients 4 to 63 years old with complete androgen insensitivity
      were extracted from an institutionally approved database. We determined whether
      each patient underwent vaginoplasty, age at vaginoplasty, vaginal depth before
      vaginoplasty, age at gonadectomy and whether the patient was sexually active.
      These data were pooled with those from a prior study at our institution to yield
      a total of 29 patients. RESULTS: All patients had undergone gonadectomy with no
      evidence of malignancy in any pathology specimens. Of the 27 patients in whom the
      date of surgery was known 20 underwent surgery in late adolescence/adulthood,
      while 7 had the testes removed in childhood. Of the 29 patients 11 (38%) have
      undergone vaginal reconstruction. Average vaginal depth in postpubertal patients
      without reconstruction was 6.6 cm (range 1.5 to 10). Preoperative vaginal depth
      in patients with was between 2 and 4 cm. Ten postpubertal patients have undergone
      vaginoplasty and 7 (70%) are sexually active. Of the postpubertal patients 15
      have not undergone vaginoplasty, of whom 12 (80%) are sexually active.
      CONCLUSIONS: A delayed approach to gonadectomy and vaginal reconstruction
      respects patient autonomy and allows a more mature patient to handle the
      psychological and physical trauma of surgery and rehabilitation. Since we
      recognize the small number of patients in this series, strict guidelines cannot
      be proposed.

PMID- 18715584
TI  - Adding renal scan data improves the accuracy of a computational model to predict
      vesicoureteral reflux resolution.
AB  - PURPOSE: We previously developed a computational model to predict vesicoureteral
      reflux resolution 1 and 2 years after diagnosis. Previous studies suggest that an
      abnormal renal scan may be a predictor of the failure of vesicoureteral reflux to
      resolve. We investigated whether the addition of renal scan data would improve
      the accuracy of our computational model. MATERIALS AND METHODS: Medical records
      and renal scans were reviewed on 161 children, including 127 girls and 34 boys,
      with primary reflux between 1988 and 2004. In addition to the 9 input variables
      from our prior model, we added renal scan data on decreased relative renal
      function (40% or less in the refluxing kidney) and renal scars. Resolution
      outcome was evaluated 1 and 2 years after diagnosis. Data sets were prepared for
      1 and 2-year outcomes, and randomized into a modeling set of 111 and a cross
      validation set of 50. The model was constructed using neUROn++. RESULTS: A
      logistic regression model had the best fit with an ROC area of 0.945 for
      predicting reflux resolution in the 2-year model. This was improved compared to
      our previous model without renal scan data. A prognostic calculator using this
      model can be deployed for availability on the Internet, allowing input variables
      to be entered and calculating the odds of resolution. CONCLUSIONS: This
      computational model uses multiple variables, including renal scan data, to
      improve individualized prediction of early reflux resolution with almost 95%
      accuracy. The prognostic calculator is a useful tool for predicting
      individualized vesicoureteral reflux resolution.

PMID- 18715586
TI  - Endoscopic subureteral injection is not less expensive than outpatient open
      reimplantation for unilateral vesicoureteral reflux.
AB  - PURPOSE: Extravesical ureteral reimplantation and subureteral Deflux injection
      are used to correct vesicoureteral reflux with success rates of 94% to 99% and up
      to 89%, respectively. It was reported that unilateral extravesical reimplantation
      may be performed safely in an outpatient setting. Given that, we analyzed total
      system reimbursement to compare planned outpatient unilateral extravesical
      reimplantation to subureteral Deflux injection in patients with unilateral
      vesicoureteral reflux. MATERIALS AND METHODS: Data were collected on consecutive
      patients undergoing outpatient procedures for unilateral vesicoureteral reflux.
      Assessment of total system reimbursement was made using a payer mix adjusted
      calculation of surgery plus anesthesia plus hospital reimbursement. This was
      compared per procedure and in terms of total system reimbursement for each
      approach to obtain a similar resolution rate. RESULTS: A total of 209 consecutive
      patients were identified, of whom 26 underwent subureteral Deflux injection and
      183 underwent unilateral extravesical reimplantation. Mean operative time was 93
      minutes for reimplantation and 45 minutes for injection. The mean volume of
      dextranomer-hyaluronic acid was 1.2 ml. Total initial system reimbursement per
      patient was $3,813 for reimplantation and $4,259 for injection. A 3% hospital
      admission rate for reimplantation increased the total to $3,945. Higher
      reimbursement for injection depended largely on the material expense for
      dextranomer-hyaluronic acid. CONCLUSIONS: In terms of total system reimbursement
      it is less expensive in our system to treat unilateral vesicoureteral reflux with
      unilateral extravesical reimplantation than with subureteral Deflux injection
      using dextranomer-hyaluronic acid. The ability to perform unilateral
      reimplantation as an outpatient procedure has shifted this relationship.

PMID- 18715588
TI  - Abnormal renal scans and decreased early resolution of low grade vesicoureteral
      reflux.
AB  - PURPOSE: Limited studies suggest a relationship between scarring on renal scan
      and failure to resolve vesicoureteral reflux. We evaluated the impact of abnormal
      renal scans on early vesicoureteral reflux resolution. MATERIALS AND METHODS: The
      medical records and renal scans were reviewed of children diagnosed with primary
      reflux between 1988 and 2004. We defined an abnormal renal scan as renal scarring
      or relative renal function 40% or less. Reflux resolution was noted 1 and 2 years
      after diagnosis. RESULTS: Renal scan data were available on 161 children with
      vesicoureteral reflux, including 127 girls and 34 boys. Relative renal function
      was 15% or less in 7 children, 16% to 35% in 14, 36% to 40% in 18 and greater
      than 40% in 122. Of the 161 patients 79 (43%) had an abnormal renal scan,
      including 37% with grades 1 to 3 reflux. The rate of 2-year reflux resolution in
      the abnormal and normal renal scan groups was 13% vs 53%. Of children with grades
      II and III reflux those with an abnormal renal scan were less likely to have
      reflux resolution compared to those with normal renal scans (23% vs 55% and 4% vs
      41, respectively, p <0.05). The same relationship was present at 1 year for
      grades 2 and 3 (18% vs 49% and 4% vs 30, respectively, p <0.05). CONCLUSIONS:
      Abnormal renal scans are an important independent predictor of early failure to
      resolve vesicoureteral reflux. An abnormal renal scan should be considered when
      counseling families about the likelihood of early reflux resolution. Performing a
      renal scan may be indicated in select patients.

PMID- 18715589
TI  - Complications of primary closure of classic bladder exstrophy.
AB  - PURPOSE: We report the urological, orthopedic and neurological complications of
      primary closure of classic bladder exstrophy using modern staged repair of
      exstrophy. MATERIALS AND METHODS: An approved database identified 137 males and
      57 females with classic bladder exstrophy who underwent primary repair by 1 of 2
      surgeons in 23 years. A total of 185 patients underwent primary closure using
      modern staged repair of exstrophy with or without osteotomies, whereas 9
      underwent delayed primary closure with epispadias repair at age 12 months. Of the
      patients 63 received osteotomies. Mean age at closure was 60 days and mean
      followup was 9 years. RESULTS: There were 14 major complications (11%) and 27
      minor complications (14%). Major urological complications included bladder
      prolapse or dehiscence in 6 male patients (3%), which was successfully reclosed.
      Major orthopedic complications, including osteotomy nonunion in 2 cases, leg
      length inequality in 1 and persistent joint pain in 1, developed in 4 of the 63
      patients (6%) who underwent osteotomy. Major neurological complications included
      femoral nerve palsy in 4 patients (2%). There were 21 minor urological
      complications (11%), including posterior bladder outlet obstruction in 4 cases,
      urethrocutaneous fistula in 2, suprapubic tube removal in 2, intrapubic stitch
      erosion in 4, febrile urinary tract infection in 6 and surgical site infection in
      3. Six patients (3%) had minor orthopedic complications, including pelvic
      osteomyelitis in 1, pin site infection in 3 and a pressure sore from
      immobilization in 1. CONCLUSIONS: Closure of bladder exstrophy is a safe surgery
      with an acceptable risk of complications. A critical review of outcomes provides
      insight to further refine the technique and manage complications when they
      develop.

PMID- 18715590
TI  - Suicide and suicidal ideation in classic exstrophy.
AB  - PURPOSE: Currently chronic illness is not a recognized risk factor for suicide in
      children. Therefore, we evaluated vulnerability for suicidal behavior (suicide
      attempt and suicidal ideation) in our population of young patients with classic
      bladder exstrophy. MATERIALS AND METHODS: We reviewed the charts of 121 patients
      5 to 24 years old with classic bladder exstrophy only from a combined, 2-center
      database of 935. These patients were psychologically evaluated from 1996 to 2005
      for preoperative readiness for urological surgery or for coping with
      medicosurgical health requirements. RESULTS: Of 121 patients 18 (14.9%)
      experienced suicidal ideation. Of 38 patients (31.4%) older than 14 years 11
      experienced suicidal ideation, 2 experienced a serious suicidal attempt and 1
      completed suicide. In 36 patients (30%) there were no recorded data on suicidal
      behavior. All patients with suicidal behavior were male. CONCLUSIONS: Data from
      this study of classic exstrophy imply that there are clinically significant
      vulnerabilities for suicidal behavior in affected male children, adolescents and
      young adults. These findings argue for screening those with classic exstrophy for
      suicidal behavior and psychopathology.

PMID- 18715592
TI  - Varicocele in adolescents: a 6-year longitudinal and followup observational
      study.
AB  - PURPOSE: Through a school screening program for varicocele we studied the
      prognostic value of hemodynamic vs clinical grading for predicting the risk of
      progression, time to worsening and the final outcome in adolescents with
      varicocele. MATERIALS AND METHODS: A school screening program was set up for boys
      between ages 10 and 16 years to assess pubertal development, varicocele,
      testicular vein reflux and testicular volume. Those who eventually had
      ipsilateral testicular hypotrophy underwent surgery. All patients underwent semen
      analysis after age 18 years. Varicocele grade was correlated with pubertal
      development, testicular vein reflux and semen quality in all groups, whether
      treated or untreated. RESULTS: A total of 2,107 boys were screened, of whom 609
      had a varicocele. By the end of the study 92 patients (15.1%) had undergone
      surgery. Hypotrophy correlated with spontaneous testicular vein reflux (high
      grade) in all cases. Semen analysis showed abnormal results in 36% treated and
      20% untreated patients. CONCLUSIONS: Children with varicocele should be regularly
      monitored to identify varicocele grade, testicular volume and vein reflux grade,
      and management should be determined accordingly. Spontaneous venous reflux toward
      the testis independent of varicocele grade closely correlates with the onset of
      testicular hypotrophy and abnormal semen analysis.

PMID- 18715596
TI  - Overview of integrative tools and methods in assessing ecological integrity in
      estuarine and coastal systems worldwide.
AB  - In recent years, several sets of legislation worldwide (Oceans Act in USA,
      Australia or Canada; Water Framework Directive or Marine Strategy in Europe,
      National Water Act in South Africa, etc.) have been developed in order to address
      ecological quality or integrity, within estuarine and coastal systems. Most such
      legislation seeks to define quality in an integrative way, by using several
      biological elements, together with physico-chemical and pollution elements. Such
      an approach allows assessment of ecological status at the ecosystem level
      ('ecosystem approach' or 'holistic approach' methodologies), rather than at
      species level (e.g. mussel biomonitoring or Mussel Watch) or just at chemical
      level (i.e. quality objectives) alone. Increasing attention has been paid to the
      development of tools for different physico-chemical or biological (phytoplankton,
      zooplankton, benthos, algae, phanerogams, fishes) elements of the ecosystems.
      However, few methodologies integrate all the elements into a single evaluation of
      a water body. The need for such integrative tools to assess ecosystem quality is
      very important, both from a scientific and stakeholder point of view. Politicians
      and managers need information from simple and pragmatic, but scientifically sound
      methodologies, in order to show to society the evolution of a zone (estuary,
      coastal area, etc.), taking into account human pressures or recovery processes.
      These approaches include: (i) multidisciplinarity, inherent in the teams involved
      in their implementation; (ii) integration of biotic and abiotic factors; (iii)
      accurate and validated methods in determining ecological integrity; and (iv)
      adequate indicators to follow the evolution of the monitored ecosystems. While
      some countries increasingly use the establishment of marine parks to conserve
      marine biodiversity and ecological integrity, there is awareness (e.g. in
      Australia) that conservation and management of marine ecosystems cannot be
      restricted to Marine Protected Areas but must include areas outside such
      reserves. This contribution reviews the current situation of integrative
      ecological assessment worldwide, by presenting several examples from each of the
      continents: Africa, Asia, Australia, Europe and North America.

PMID- 18715597
TI  - Status of organic pollutants in surface sediments of Barnegat Bay-Little Egg
      Harbor Estuary, New Jersey, USA.

PMID- 18715598
TI  - Evaluation of stony coral indicators for coral reef management.
AB  - Colonies of reef-building stony corals at 57 stations around St. Croix, US Virgin
      Islands were characterized by species, size and percentage of living tissue.
      Taxonomic, biological and physical indicators of coral condition were derived
      from these measurements and assessed for their response to gradients of human
      disturbance-a requirement for indicators used in regulatory assessments under
      authority of the Clean Water Act. At the most intensely disturbed location, five
      of eight primary indicators were highly correlated with distance from the source
      of disturbance: Coral taxa richness, average colony size, the coefficient of
      variation of colony size, total topographic coral surface area, and live coral
      surface area. An additional set of exploratory indicators related to rarity,
      reproductive and spawning mode and taxonomic identity were also screened. The
      primary indicators demonstrated sufficient precision to detect levels of change
      that would be applicable in a regional-scale regulatory program.

PMID- 18715599
TI  - Composition of the water accommodated fractions as a function of exposure times
      and temperatures.
AB  - The water accommodated fractions (WAFs) of nine oils in seawater have been
      studied. The oils range from light condensate to heavy crude, and include one
      highly biodegraded oil and one very wax rich oil. This study has identified large
      variations in the chemical composition of WAFs, depending on oil type,
      temperature, and mixing time. Experiments at different temperatures (2-13 degrees
      C) showed that it takes longer time to reach equilibrium at the lowest
      temperatures, and that this varies for the different oil types. Oils with higher
      pour point (wax rich oils) need a longer time to establish WAF in equilibrium
      than oils with lower pour points (naphthenic oils). At 13 degrees C a mixing time
      of 48h, as recommended in standard procedures, seems to be sufficient for
      asphalthenic and paraffinic oils. The results demonstrated that for WAF prepared
      from an unknown oil, or at lower temperatures, different mixing times should be
      tested. Since the WAF often is used in toxicity testing, the toxicity might be
      underestimated if the mixing time is too short.

PMID- 18715600
TI  - Sesquiterpene lactones and their precursors as chemosystematic markers in the
      tribe Cichorieae of the Asteraceae.
AB  - This review summarizes all reports on sesquiterpene lactones and their immediate
      precursors from the Cichorieae (Lactuceae) tribe of the Asteraceae. A total of
      360 compounds have been reported from this tribe. The reported substances belong
      to three classes of sesquiterpenoids: guaianolides (243 compounds),
      eudesmanolides (73 compounds), and germacranolides (44 compounds). Sources of
      these compounds encompass 139 taxa from 31 different genera. The distribution of
      these lactones within the tribe Cichorieae is discussed in a chemosystematic
      context. Moreover, some general ideas about the interpretation of chemosystematic
      data are discussed.

PMID- 18715601
TI  - A triterpenoidal saponin and sphingolipids from Pteleopsis hylodendron.
AB  - From the stem bark of Pteleopsis hylodendron, a triterpenoidal saponin
      bellericagenin [B 3-O-[beta-D-glucopyranosyl-(1-->2)-alpha-D-glucopyranoside] (1)
      (Pteleopsoside)] and two sphingolipids, hylodendroside-I (2), and hylodendroside
      II (3) were isolated, along with a synthetically known compound, [2alpha, 3beta,
      23-triacetoxy-19alpha-hydroxyolean-12-en-28-oic acid (4)]. Other known compounds,
      friedelin (5), beta-carotene (6), lupeol (7), sitosterol (8), and stigmasterol
      (9), were also obtained. Their structures were deduced with the help of detailed
      spectroscopic studies.

PMID- 18715602
TI  - Detection of papillomaviral DNA sequences in a feline oral squamous cell
      carcinoma.
AB  - Oral squamous cell carcinomas (OSCCs) are common and often fatal feline
      neoplasms. Factors that predispose to neoplasm development in cats are poorly
      defined. Around 25% of human OSCCs are caused by papillomaviruses (PVs). To
      determine if PVs are associated with OSCCs in cats, three sets of consensus
      primers were used to evaluate 20 feline OSCCs and 20 non-neoplastic feline oral
      lesions for the presence of PV DNA. Papillomaviral sequences were detected within
      one OSCC, but no non-neoplastic lesion. Sequencing of the amplified DNA revealed
      a previously unreported PV that was most similar to human PV type 76. This is the
      first time PV DNA has been amplified from the oral cavity of a cat. However,
      while these results suggest that feline gingival epithelial cells can be infected
      by PVs, they do not support a causal association between viral infection and the
      development of feline OSCCs.

PMID- 18715603
TI  - [Epidemiology of maxillofacial traumatology in Tunis].
AB  - INTRODUCTION: The aim of this study was to assess the epidemiology of
      maxillofacial trauma in Tunisia over a 10-year period. METHODS: This
      retrospective study was carried out between 1995 and 2004 on patients admitted
      for maxillofacial trauma in the department of maxillofacial and plastic surgery
      of the Charles-Nicolle Hospital in Tunis. The selected relevant parameters were:
      age, gender, etiology, time of trauma, type of fracture and associated lesions.
      RESULTS: A total of 1100 patient files were analyzed. The average age was 29
      years and the sex-ratio was 6:1 in favor of men. The most common etiologies were:
      car crashes (39%), fights (28%) and domestic trauma (19%), occurred in the
      evening, on weekends and in the summer. The frequency increased in the evening,
      on weekends and in the summer. Mandibular fractures (62%) and zygomatic fractures
      (32%) were the most common trauma. Polytrauma occurred in 18% of the patients and
      cranial trauma in 10% of the cases. DISCUSSION: Epidemiological investigations
      results vary according to demographic and cultural regional specificities. Long
      term collection of epidemiological data in maxillofacial surgery is a major issue
      to plan educational campaigns and therapeutic strategies. In Tunisia, driver
      education and observance of traffic regulations should be improved.

PMID- 18715604
TI  - Cutaneous leishmaniasis caused by Leishmania tropica in Algeria.
AB  - Cutaneous leishmaniasis is endemic in Algeria, but clinical and parasitological
      data from this area are scarce. In order to document the transmission of this
      disease in a peri-urban setting, cutaneous lesions from patients living in
      Constantine City and surrounding areas were spotted on filter paper for diagnosis
      and species identification using real-time PCR. Surprisingly, Leishmania tropica
      was detected in 6/69 patients, and confirmation was obtained by sequencing. This
      observation suggests a modification of the epidemiology of cutaneous
      leishmaniasis in Algeria and should alert physicians and policy-makers to the
      risk of antimony treatment failure with this species.

PMID- 18715605
TI  - Different evolutionary rates and epidemic growth of hepatitis B virus genotypes A
      and D.
AB  - The epidemiological history of HBV genotypes A and D and subgenotypes A2 and D3
      was studied on 132 isolates drawn between 1980 and 2005 from patients living in a
      homogenous geographical area. Evolutionary rates and divergence dates were
      estimated and HBV demographic history was reconstructed by using a statistical
      approach based on coalescent theory. The evolutionary rate of A2 was
      significantly lower than that of D3. The growth rate of D3 epidemic was
      significantly faster than that of A2; both subgenotypes showed a decreasing
      growth rate from the mid-1980s. Our data suggest that the important discrepancies
      observed in the evolutionary rates of HBV genotypes A and D may reflect different
      population dynamics of their epidemics. These results show the usefulness of
      phylodynamic studies in reconstructing the history of epidemics due to highly
      variable DNA viruses, and in evaluating the long-term efficacy of prophylactic
      measures.

PMID- 18715606
TI  - Influence of interactions between NOM and particles on UF fouling mechanisms.
AB  - This study focused on the mechanistic effects of molecular interactions between
      inorganic particles (kaolinite) and the two main NOM fouling fractions of
      polysaccharides (alginate) and humics (humic acids) in ultrafiltration. Fouling
      effects were studied during the dead-end filtration of individual and mixed
      compounds as well as during the subsequent filtration of individual compounds.
      SEM analyses were performed to further study the fouling-layer structure. A
      significant synergistic effect was observed during combined particle-NOM fouling,
      which was considerably greater than the sum of particle and organic fouling
      alone. Synergistic fouling could be explained by NOM-particle interactions in the
      feed solution and during the fouling process. Kaolinite alone formed a fouling
      layer of particle aggregates, whereas humic acid adsorption onto kaolinite
      resulted in a fouling layer of stabilized colloids of humic acid and kaolinite.
      In the case of alginate, simultaneous pore-blocking and cake-layer formation of
      NOM and kaolinite dominated the fouling. In both cases, incorporation of the
      organics in the kaolinite fouling layer resulted in a fouling cake of
      significantly reduced porosity compared to individual particle filtration.
      Irreversible fouling by NOM could not be prevented by kaolinite. SEM images
      showed patches of the particle-fouling layer remaining on the membrane surface
      after backwashing, which can be linked to particle-membrane associations by NOM
      bridging.

PMID- 18715607
TI  - Coagulation behavior of Al(13) aggregates.
AB  - The coagulation behavior of Al(13) aggregates formed in coagulation of kaolin was
      investigated by small angle static light scattering (SASLS), solid-state (27)Al
      NMR and tapping mode atomic force microscope (TM-AFM). A kaolin suspension was
      coagulated by PACl containing high content of Al(13) polycation (PACl-Al(13)).
      The results indicated that Al(13) was predominant in destabilizing kaolin
      particles for PACl-Al(13) coagulation even though at alkaline pH (pH 10). At such
      high pH, Al(13) aggregates were observed when the dosage of PACl-Al(13) was
      increased. In addition, the mechanism of coagulation by PACl-Al(13) at alkaline
      pH was affected by dosage. When the dosage was insufficient, coagulation was
      caused by electrostatic patch, which led to compact flocs with high fractal
      dimension (D(f)). Interparticle bridging dominated the coagulation when the
      coagulant dosage approached the plateau of adsorption, which caused the looser
      flocs with low D(f). The in-situ AFM scanning in liquid system proved that the
      existence of linear Al(13) aggregates composed of a chain of coiled Al(13) in
      coagulation by PACl-Al(13) at a high dosage and alkaline pH. Meanwhile, several
      coiled Al(13) aggregates with various dimensions were observed at such condition.

PMID- 18715608
TI  - Concentrations of PCDD/PCDFs in plasma of subjects living in the vicinity of a
      hazardous waste incinerator: follow-up and modeling validation.
AB  - In 2007, the concentrations of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/PCDFs) were determined in plasma of non-occupationally
      exposed subjects living near the only hazardous waste incinerator (HWI) in Spain
      (Constanti, Tarragona County, Catalonia). These data were compared with the
      levels found in two previous surveys performed in 1998 (baseline) and 2002. The
      current mean PCDD/PCDF concentration in plasma was 9.36pg I-TEQg(-1) of lipid
      (range: 1.76-23.44pg I-TEQg(-1) of lipid). It means a significant reduction of
      the mean PCDD/PCDFs levels in plasma in comparison to the concentrations found in
      1998 and 2002 (27.01 and 15.70pg I-TEQg(-1) of lipid, respectively). This
      important decrease agrees well with the notable reduction in the dietary intake
      of PCDD/PCDFs recently noted for the population of the same area (210.1pg I-TEQd(
      1), 63.8pgWHO-TEQd(-1), and 27.8pgWHO-TEQd(-1), in 1998, 2002 and 2007,
      respectively). The current data were also used to predict theoretical PCDD/PCDF
      concentrations in plasma by executing a single-compartment empirically-based
      pharmacokinetic model on the basis of the daily intake of these pollutants by the
      local population.

PMID- 18715609
TI  - Evaluation of carbon degradation during co-composting of exhausted grape marc
      with different biowastes.
AB  - In this work the carbon biodegradation of exhausted grape marc (EGM) combined
      with other organic wastes using the turned pile composting system was studied.
      Four different piles were made of EGM in Pile 1, EGM mixed with cow manure and
      straw (CMS) in Pile 2, EGM mixed with municipal solid waste (MSW) in Pile 3 and
      EGM mixed with grape stalks (GS) in Pile 4. The results obtained were modelled to
      determine the main kinetic and stoichiometric parameters. Regarding to the rate
      constants of the composting processes they were increased from 0.033d(-1), the
      value obtained when EGM was composted alone, to 0.040 and 0.044d(-1) when MSW and
      GS were added, respectively as co-substrates. However, the addition of CMS
      reduced the rate constant. About the biodegradable carbon fractions, it was
      observed that the co-composting reduced significantly the remanent carbon
      concentration after composting in all the piles whilst increased the readily
      biodegradable carbon fractions from 35, the value obtained when EGM was composted
      alone, to 50 and 60%, respectively when MSW or GS were added. As regards the
      temperature profiles, only Piles 1 and 4 achieved thermal hygienization values
      and about the nitrogen losses, the lowest percentage of nitrogen loss took place
      when GS were added, because of its optimum pH and C/N initial ratio. Thus, though
      any of these wastes could be used for co-composting with EGM, the use of GS as co
      substrate and bulking agent for the co-composting process of EGM was recommended.

PMID- 18715610
TI  - Surface water concentrations of the fragrance compound OTNE in Germany--a
      comparison between data from measurements and models.
AB  - Emissions of the fragrance compound OTNE (Iso-E-Super) to surface waters have
      been investigated by means of a combined analytical (measurements) and modeling
      approach. The compound is an ingredient in many household products and is emitted
      into surface waters almost exclusively via the wastewater pathway. Measured
      concentrations of OTNE in surface waters of the Ruhr river catchment basin ranged
      from 30 to 100 ng L(-1), and were thus in the same order of magnitude as the
      polycyclic musks AHTN and HHCB. The geo-referenced exposure model GREAT-ER (Geo
      referenced Regional Exposure Assessment Tool for European Rivers) was used to
      simulate OTNE concentrations in the Ruhr river basin. Model results could
      plausibly explain monitoring data at all sampling sites when considering the
      discharge conditions during the sampling period and specific local
      characteristics. According to the model, approximately half of the total OTNE
      emissions into the Ruhr river basin are transferred from surface water into the
      atmosphere and the sediment. Volatilization from lakes was identified as the
      major removal process of the fragrance compound OTNE. To identify possible
      regional differences, samples from the Danube in Hungary were also analysed. The
      OTNE concentrations were in the same order of magnitude (29-810 ng L(-1)) as in
      the Ruhr catchment, but exhibited higher spatial variability.

PMID- 18715611
TI  - Biodegradation of oxygenated and non-oxygenated imidazolium-based ionic liquids
      in soil.
AB  - Aerobic biodegradation of ionic liquids in soil was monitored for the first time.
      The tests, followed over six months according to ASTM D 5988-96, were carried out
      on the four ionic liquids obtained from 1-R-3-methylimidazolium cations, with
      R=CH(3)(CH(2))(3) and CH(3)O(CH(2))(2), and the tetrafluoroborate and dicyanamide
      counter anions. The n-butyl derivatives, after an induction period of about two
      months, were found to be degradable, although the degradation rate with the
      dicyanamide anion was smaller. In contrast, no significant production of CO(2)
      was observed in the tests with the methoxyethyl derivatives. Calculations at the
      B3LYP/6-31G(d) level were carried out to characterize the atomic charge
      distributions and frontier orbital structures of 1-alkyl-3-methylimidazolium
      cations and point out the changes caused by replacement of a CH(2) group of the
      alkyl chain with an oxygen atom. The calculations predict an overall negative
      charge on the nitrogen atoms of the imidazolium-based cations. The energies of
      the highest occupied (pi) MO and lowest empty (pi( *)) MO are only slightly
      perturbed by the length and nature of the alkyl chain. However, the electron
      donor properties of the oxy derivatives are radically increased. The HOMO becomes
      a lone pair orbital mainly localized on the oxygen atom, and its ionization
      energy is sizeably smaller than that of the outermost ring pi MO.

PMID- 18715612
TI  - Improved histologic and clinicopathologic criteria for prognostic evaluation of
      pancreatic endocrine tumors.
AB  - Currently used histopathologic criteria for the diagnosis of pancreatic endocrine
      tumors are still under discussion as far as to their capacity to identify
      prognostically different tumor subsets, which are potentially helpful for patient
      management. A recently developed TNM staging system and a variety of proposed
      histologic and clinicopathologic parameters still need to be fully validated. One
      hundred fifty-five pancreatic endocrine tumors encompassing all the main
      histologic types and stages, operated with intention to cure and then followed up
      for a median 126 months, were carefully investigated histologically to identify
      prognostically informative parameters at univariable, bivariable, and
      multivariable analysis. Ki67 index, mitotic rate, neuroinvasion with or without
      vascular, peritumoral or stromal infiltrative patterns, as well as tumor size,
      and association with endocrine syndromes other than insulinoma proved effective
      in predicting recurrence and disease-specific death among well-differentiated
      tumors. Poorly differentiated histologic features, more than 10 mitoses/10 high
      power fields, and necrosis were helpful in the identification of high-grade
      cancers with an invariably poor prognosis. The TNM system proved to be highly
      predictive of patient outcome and easy to combine with histologic and
      clinicopathologic parameters to classify pancreatic endocrine tumors into groups
      of increasing malignant potential.

PMID- 18715613
TI  - Bone metastasis is strongly associated with estrogen receptor
      positive/progesterone receptor-negative breast carcinomas.
AB  - Bone is one of the most common sites of distant metastasis for breast carcinomas.
      In this study, our objective is to identify molecular markers and molecular
      subtypes that may predict patients at higher risk of developing bone metastasis.
      Immunohistochemical analysis with antibodies against estrogen receptor alpha,
      progesterone receptor, androgen receptor, Her2/neu, epidermal growth factor
      receptor, CK5/6, CK14, CK17, CK8, and CK18 was performed on representative
      sections of 21 breast carcinomas with bone metastasis and 94 cases without bone
      metastasis. The expression rates of receptors, subtype distributions (basal
      versus nonbasal) of 3 molecular classifications (cytokeratin, triple negative,
      and cytokeratin/triple negative), and 5 subtypes of cytokeratin/triple negative
      classification were compared between these 2 groups. We found that (1) the breast
      cancers with bone metastasis were associated with a significant percentage of
      estrogen receptor-positive/progesterone receptor-negative tumors compared with
      tumors without bone metastasis (38% versus 6%, P < .0001). (2) There was
      significant difference on estrogen receptor expression between high grade and non
      high grade in tumors with or without bone metastasis (P = .0084 and 1.0000,
      respectively). (3) The breast cancers with bone metastasis were more likely to be
      estrogen receptor positive (85%) and androgen receptor positive (95%) compared
      with those without bone metastasis (59% and 74%, respectively, both P < .05). (4)
      There was no significant difference between tumors with or without bone
      metastasis in subtype distribution (basal versus nonbasal) among all 3 molecular
      classifications. (5) Luminal B carcinomas of cytokeratin/triple negative
      classification tended to be associated with bone metastasis but not to a
      statistically significant extent. In conclusion, bone metastasis is strongly
      associated with estrogen receptor-positive/progesterone receptor-negative tumors.
      Significant difference in estrogen receptor expression between high-grade and non
      high-grade tumors with bone metastasis suggests that different panels of
      molecular markers should be used to predict bone metastasis in these 2 groups of
      tumors.

PMID- 18715614
TI  - Diverticular disease of the vermiform appendix: a diagnostic clue to underlying
      appendiceal neoplasm.
AB  - Acquired diverticula of the vermiform appendix are rare and arise as a result of
      different pathogenetic mechanisms. One of the etiologies includes proximally
      located, often unsuspected small neoplasms. Although the association of
      appendiceal diverticulosis and neoplasia is known, it remains underemphasized in
      the teaching and practice of surgical pathology. To investigate the frequency of
      appendiceal neoplasms with acquired diverticulosis, we conducted a retrospective
      analysis of all appendectomy specimens received in our institution for a 55-month
      period (January 2002-July 2006). A total of 1361 appendectomy specimens were
      identified. Diverticulosis was diagnosed in 23 (1.7%) of all cases. Eleven (48%)
      appendectomy specimens with diverticulosis also harbored an appendiceal neoplasm.
      The association of appendiceal neoplasms with diverticulosis was statistically
      significant (P < .0001, 2-sided Fisher exact test). Neoplastic processes included
      5 well-differentiated neuroendocrine tumors (carcinoids), 3 mucinous adenomas, 1
      tubular adenoma, and 2 adenocarcinomas. In one case, routine representative
      sections sampled only a small focus of carcinoma, which originally went
      undiagnosed. We stress the need for meticulous gross assessment with histologic
      examination of the entire appendectomy specimen in cases of appendiceal
      diverticulosis. Thorough examination is required to rule out an underlying
      neoplasm as a cause of diverticulosis. As acquired diverticula represent a rare
      finding, examination of the entire appendix in this setting does not create a
      significant impact on the workload within the pathologic laboratory.

PMID- 18715615
TI  - Necrotizing villitis and decidual vasculitis in the placentas of mothers with
      Behcet disease.
AB  - Behcet disease is an inflammatory disorder characterized by recurrent aphthous
      stomatitis, genital ulcers, uveitis, and skin lesions. There are occasional
      reports of neonatal Behcet disease suggesting a possible prenatal transmission.
      However, no placental Behcet disease lesion has been reported. Here, we report
      characteristic necrotizing inflammation in placentas and decidua from 2 patients
      with Behcet disease. The first patient had full-term delivery after uneventful
      medical therapy. The second patient underwent therapeutic abortion in the first
      trimester because of the fetal exposure to a potentially harmful medication for
      Behcet disease. Both placentas showed focal necrotizing villitis with neutrophil
      dominant infiltration, similar to the characteristic Behcet disease lesions in
      other organs. Intervillous fibrinous exudates with neutrophilic infiltrates and
      granuloma-like histiocytic aggregates were present. The decidua also showed
      neutrophilic vasculitis. No evidence of infection was present. Our observation
      suggests that Behcet disease may involve placentas from the early stage of
      pregnancy. It may be implicated in potential fetal compromise and/or intrauterine
      transmission of the disease.

PMID- 18715616
TI  - Expression of cyclin D1 splice variants is differentially associated with outcome
      in non-small cell lung cancer patients.
AB  - Real-time reverse transcription polymerase chain reaction and
      immunohistochemistry were used to evaluate the messenger RNA (mRNA) and protein
      expression levels of total cyclin D1 and its splice variants (cyclin D1a and
      cyclin D1b) in 102 paired malignant and nonmalignant tissues from patients with
      non-small cell lung cancer, respectively. The expression levels of total cyclin
      D1 and its splice variants were significantly up-regulated in malignant tissues
      than in nonmalignant tissues at both mRNA and protein levels. Although the
      expression levels of cyclin D1a were higher than those of cyclin D1b, the
      relative expression ratios of cyclin D1b mRNA between malignant and nonmalignant
      lung tissues were obviously higher than those of cyclin D1a mRNA. Analysis of
      variance showed that cyclin D1b mRNA expression was significantly associated with
      the histologic grade, lymph node metastasis, distant metastasis, and tumor stage
      of patients, whereas cyclin D1a mRNA expression was not related to
      clinicopathologic characteristics except sex. Patients with cyclin D1b mRNA
      expression above the median value had shorter survival than those below the
      median value (P = .033). Similarly, cyclin D1b immunopositivity was also
      associated with histologic grade, and patients with immunostaining positivity for
      cyclin D1b showed poor survival (P = .005). Multivariate analysis demonstrated
      that cyclin D1b immunopositivity was an independent risk factor in survival of
      patients with non-small cell lung cancer (P = .018). Our data show that cyclin
      D1b, rather than canonical cyclin D1a, might contribute to the development of non
      small cell lung cancer. Cyclin D1b would be a better prognostic indicator for non
      small cell lung cancer as compared to total cyclin D1 or cyclin D1a.

PMID- 18715617
TI  - Clinicopathologic significance of mitotic arrest defective protein 2
      overexpression in hepatocellular carcinoma.
AB  - Mitotic arrest defective protein 2 (MAD2) gene plays a central role in the
      mitotic checkpoint. Elevated MAD2 expression was observed in a number of human
      malignancies; its role in the development of hepatocellular carcinoma is still
      not understood and is controversial. The purpose of this study was to investigate
      the clinicopathologic significance of MAD2 expression in hepatocellular
      carcinoma. The MAD2 protein and its messenger RNA levels were measured in
      hepatocellular carcinomas, high-grade dysplastic nodules, and their paired
      nontumorous liver tissues by quantitative real-time polymerase chain reaction,
      Western blot, and immunohistochemistry. The results showed that MAD2 at both
      messenger RNA and protein levels was overexpressed in 8 of 9 high-grade
      dysplastic nodules and in 51 of 58 hepatocellular carcinomas, including 12 of 14
      unifocal small hepatocellular carcinomas. There was a tendency for MAD2
      expression to increase in the process of this multistep carcinogenesis. A
      significantly high tumor MAD2 immunostaining was associated with the progression
      of histologic grade and the overall low survival. In conclusion, MAD2 is
      overexpressed frequently in hepatocellular carcinoma, including high-grade
      dysplastic nodules and early-stage small hepatocellular carcinoma, indicating
      that overexpression of MAD2 plays a role in the development and progression of
      hepatocellular carcinoma. It may be an early event in hepatocarcinogenesis and
      could be used as a potential prognostic indicator.

PMID- 18715618
TI  - Correlation between beta-catenin widespread nuclear expression and matrix
      metalloproteinase-7 overexpression in sporadic desmoid tumors.
AB  - Desmoid tumors (desmoid-type fibromatoses) are locally aggressive soft tissue
      tumors associated with the Wnt/beta-catenin signaling pathway (APC-beta-catenin
      Tcf pathway). Matrix metalloproteinase-7, which is one of the target genes of the
      Wnt/beta-catenin signaling pathway, has been reported to play an important role
      in tumor progression. We examined the immunohistochemical expression of beta
      catenin and matrix metalloproteinase-7 in 72 samples (63 primary and 9 recurrent
      samples, 63 patients) of sporadic desmoid tumors without familial adenomatous
      polyposis, and the genetic alteration of the beta-catenin gene in 33 frozen
      materials (22 primary and 11 recurrent samples, 22 patients). We further examined
      messenger RNA expression of matrix metalloproteinase 7 by quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) and compared the results with
      those of normal skeletal muscles. Immunohistochemically, there was a
      statistically significant correlation between widespread nuclear expression of
      beta-catenin and overexpression of matrix metalloproteinase-7 (P < .01 in extra
      abdominal desmoid, Fisher test). There were 7 missense point mutations in the 22
      primary frozen samples (32%). In the beta-catenin mutated group, matrix
      metalloproteinase-7 messenger RNA expression was significantly higher than that
      of the beta-catenin wild-type group (P = .0018, Mann-Whitney U test). Our results
      suggest that the matrix metalloproteinase-7 gene may be up-regulated by mutated
      or continuously elevated beta-catenin protein and that the matrix
      metalloproteinase-7 gene may also be targeted in the Wnt/beta-catenin signaling
      pathway in sporadic desmoid tumors.

PMID- 18715619
TI  - KIT codon 558 insertions in gastrointestinal stromal tumors. Analysis of 17 rare
      KIT mutants.
AB  - Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of
      gastrointestinal tract often driven by oncogenic KIT exon 11 mutations. Although
      deletions and substitutions are most frequent KIT exon 11 mutations, duplications
      and insertions have been reported as well. In contrast to duplications, which
      cluster in 3'KIT exon 11, insertions affect 5'KIT, particularly codon 558.
      Clinicopathologic profile of gastrointestinal stromal tumors with insertions in
      codon 558 is not known. In this study, 17 gastrointestinal stromal tumors with
      codon 558 insertions are reported. Fifteen (88.2%) KIT codon 558 insertions
      consisted of 1694_1695insTCC leading to Lys558delinsAsnPro. However, 2 variant
      mutants Lys558delinsAsnGln and Lys558delinsAsnAsn were also identified. Based on
      analysis of inserted and flanking sequences, the insertions contain inverted DNA
      sequences of the opposite strand. Therefore, these insertions may develop due to
      a DNA strand switch during replication by DNA polymerases and by the effects of
      several different DNA repair processes. Patient median age was 61 years, and male
      to-female ratio was 1:1.8. gastrointestinal stromal tumors were diagnosed in
      stomach (n = 4), small intestine (n = 7), and rectum (n = 3). Three tumors were
      disseminated and primary location could not be established. Fourteen tumors had
      spindle cell morphology, and epithelioid cell features were seen in 2 intestinal
      and 1 disseminated gastrointestinal stromal tumor. Based on size and mitotic
      activity, 2 (50%) of 4 gastric and 3 (48.9%) of 7 small intestinal
      gastrointestinal stromal tumors had more than 50% risk of metastases according to
      previous studies of gastrointestinal stromal tumor prognosis. All 3 rectal
      gastrointestinal stromal tumors were malignant. Metastases were verified in 8
      (66.7%) of 12 patients with known clinical and follow-up data. In summary, KIT
      codon 558 insertions are rare mutations accounting for less than 1% of all KIT
      mutants. Gastrointestinal stromal tumors with these mutations appear to have
      predilection to female patients and intestinal location. Moreover, KIT codon 558
      insertions might indicate an increased risk of malignant behavior for gastric
      gastrointestinal stromal tumors.

PMID- 18715620
TI  - Apoptosis markers in liver biopsy of nonalcoholic steatohepatitis in pediatric
      patients.
AB  - The natural history of pediatric nonalcoholic steatohepatitis is still unknown;
      however, there are differences between adult and pediatric presentation.
      Apoptosis may play an important role in pathophysiologic pathways involved in
      liver damage and progression. Our aim was to detect early apoptosis markers,
      activated caspase-3 and cleaved cytokeratin-18, in hepatocytes and to correlate
      their presence with clinical, serologic, and histologic characteristics in
      pediatric nonalcoholic steatohepatitis. Twenty-five pediatric nonalcoholic
      steatohepatitis liver biopsies were evaluated by immunohistochemistry for
      presence of activated caspase-3 and cleaved cytokeratin-18. Biopsy specimens were
      semiquantitatively graded for activity (steatosis, inflammation, and ballooning)
      and fibrosis. Records were reviewed for serum aspartate aminotransferase, alanine
      aminotransferase, cholesterol, triglycerides, and body mass index, which was
      elevated in 92% of cases. Serum aspartate aminotransferase and alanine
      aminotransferase were elevated in 32% and 68% of cases, respectively. Sixty
      percent of biopsies exhibited lobular steatosis grade 3, 84% lobular inflammatory
      activity grade 1, 72% ballooning grade 1, and 76% fibrosis stage 3. Cleaved
      cytokeratin-18 was associated with milder fibrosis (P = .02) and inflammation (P
      = .07), although there was no association with steatosis grade. Activated caspase
      3 detection was also associated with low inflammatory grade (P = .03) but not
      with fibrosis and steatosis. This study reveals interesting differential features
      concerning nonalcoholic steatohepatitis histologic characteristics and apoptosis
      markers compared with adult cases. Because, in this pediatric series, apoptosis
      seemed to be an early event in the cascade of liver injury steps, it would be
      useful to consider caspase inhibitors as potential therapeutic strategies to
      prevent liver damage progression.

PMID- 18715621
TI  - High levels of vascular endothelial growth factor and its receptors (VEGFR-1,
      VEGFR-2, neuropilin-1) are associated with worse outcome in breast cancer.
AB  - Vascular endothelial growth factor has been shown to be up-regulated in breast
      cancers. Vascular endothelial growth factor receptors, VEGFR-1 and VEGFR-2, are
      the principal mediators of its effects. Together with VEGFR-1 and VEGFR-2,
      neuropilin-1 may act as a coreceptor for vascular endothelial growth factor.
      Although vascular endothelial growth factor exerts important effects on
      endothelial cells, VEGFRs are likely present on tumor cells as well. We used AQUA
      to analyze tumor-specific expression of vascular endothelial growth factor, VEGFR
      1, VEGFR-2, and neuropilin-1 on a large cohort of breast cancer tissue
      microarray. Two-fold redundant arrays were constructed from 642 cases of primary
      breast adenocarcinomas. Automated image analysis with AQUA (Automated
      Quantitative Analysis) was then performed to determine a quantitative expression
      score. Scores from redundant arrays were normalized and averaged. Kaplan-Meier
      survival analysis showed that high levels of vascular endothelial growth factor,
      VEGFR-1, VEGFR-2, and neuropilin-1 were all significantly associated with
      survival (Miller Siegmeund corrected P = .0020, .0160, and .0320, respectively).
      In addition, vascular endothelial growth factor and neuropilin-1 retained a
      significant association with survival independent of other standard prognostic
      factors. Vascular endothelial growth factor, VEGFR-1 and -2, and neuropilin-1 are
      expressed to varying degrees in primary breast cancers and have prognostic
      significance. Further study of the functional significance of this finding is
      warranted as well as the prognostic value of these biomarkers in other tumor
      microenvironment-specific compartments (eg, vessels).

PMID- 18715622
TI  - A quantitative method for the evaluation of three-dimensional structure of
      temporal bone pneumatization.
AB  - Temporal bone pneumatization has been included in lists of characters used in
      phylogenetic analyses of human evolution. While studies suggest that the extent
      of pneumatization has decreased over the course of human evolution, little is
      known about the processes underlying these changes or their significance. In
      short, reasons for the observed reduction and the potential reorganization within
      pneumatized spaces are unknown. Technological limitations have limited previous
      analyses of pneumatization in extant and fossil species to qualitative
      observations of the extent of temporal bone pneumatization. In this paper, we
      introduce a novel application of quantitative methods developed for the study of
      trabecular bone to the analysis of pneumatized spaces of the temporal bone. This
      method utilizes high-resolution X-ray computed tomography (HRXCT) images and
      quantitative software to estimate three-dimensional parameters (bone volume
      fractions, anisotropy, and trabecular thickness) of bone structure within defined
      units of pneumatized spaces. We apply this approach in an analysis of temporal
      bones of diverse but related primate species, Gorilla gorilla, Pan troglodytes,
      Homo sapiens, and Papio hamadryas anubis, to illustrate the potential of these
      methods. In demonstrating the utility of these methods, we show that there are
      interspecific differences in the bone structure of pneumatized spaces, perhaps
      reflecting changes in the localized growth dynamics, location of muscle
      attachments, encephalization, or basicranial flexion.

PMID- 18715623
TI  - Stone-throwing by Japanese macaques: form and functional aspects of a group
      specific behavioral tradition.
AB  - Throwing is a major behavioral component of hominid evolution. Comparison of this
      behavior across a broad range of non-human primate species is needed to elucidate
      the phylogenetic constraints on throwing behavior. In this study of stone
      throwing in Japanese macaques, we present a systematic multi-group comparison of
      the frequency and prevalence of this behavior as well as detailed descriptions
      and quantitative data on the form, context, and possible social transmission of
      stone-throwing. Stone-throws were mainly underarm, performed from a tripedal
      posture, and often accompanied by repeated vertical leaps. We found marked
      individual hand preferences for throwing, but no consistent group-level
      handedness. Our results support the hypotheses relating body posture, throwing
      style, and handedness in throwing by primates. Based on the analysis of the
      contexts that may elicit the behavior, we postulate that unaimed stone-throwing
      in Japanese macaques may serve to augment the effect of agonistic displays, and
      accordingly, can be regarded as spontaneous tool-use. Our findings are consistent
      with the comparative data using modern non-human primate species to model the
      structural processes and functional aspects of throwing evolution in early
      hominids. This study supports the view that tool-use evolves from initially non
      functional behaviors, such as stone handling, which is a form of object play.
      Stone-throwing by Japanese macaques meets several criteria of a behavioral
      tradition, including group-specificity. This first report of a stone-tool-use
      tradition in Japanese macaques is of direct relevance to the question of the
      evolution of stone technology in hominids.

PMID- 18715624
TI  - Hallucal grasping behavior in Caluromys (Didelphimorphia: Didelphidae):
      Implications for primate pedal grasping.
AB  - A key feature in primate evolution is a foot with a divergent opposable hallucal
      metatarsal bearing a large peroneal process. Extant primates are characterized by
      a powerful hallucal grasp-an either "euprimate" or "plesiadapoid-euprimate"
      ancestor acquisition-that facilitates the exploitation of fine branches, an
      ability that increased the fitness of ancestral euprimates. In this context, the
      didelphid marsupial Caluromys has been used as the extant analog to this primate
      morphotype stage due to some morphological, ecological, and behavioral features.
      However, the extent to which and the positional and support contexts in which
      Caluromys uses powerful hallucal grasping are not known. This renders analogies
      to any mode of "euprimate" or "stem primate" grasping poorly substantiated. The
      present paper quantifies locomotor and postural behavior, support use, and
      associated frequencies of hallucal grasping in captive Caluromys philander via
      analysis of video recordings. During locomotion, Caluromys primarily used
      diagonal sequence walk, clamber, and climb, whereas stand, foot-hang, and bipedal
      stand were the dominant postures. Small, fine, horizontal, and moderately
      inclined branches were frequently used. Overall rates of "apparently powerful
      hallucal grasps" were high, but were exceptionally high during clamber, climb,
      foot-hang, and bipedal stand. Additionally, an "apparently powerful hallucal
      grasp" was very common upon fine, small, steep, and vertical branches. The
      extensive use of such powerful hallucal grasping provided stability and safety
      that enabled Caluromys to proficiently utilize fine branches of various
      orientations. The ability to negotiate such unstable supports, further reflected
      in foot anatomy, provides evidence that the morphobehavioral complex of Caluromys
      can serve as an extant analog to the plesiadapoid-euprimate ancestor, represented
      as a terminal branch feeder with effective hallucal grasping.

PMID- 18715625
TI  - Nematode-based risk assessment of mixture toxicity in a moderately polluted river
      floodplain in The Netherlands.
AB  - Heavy metal polluted soils usually contain mixtures of different metals, whereas
      legislation is derived from concentrations of individual metals. The mixture
      toxicity of the Dutch floodplain Afferdensche and Deestsche Waarden was estimated
      to be high (msPAF ranged from 67-94%). Analyses of nematode community based
      bioindicators (Maturity Index, taxonomic diversity, trophic groups, multivariate
      analysis, DoFT-sentinels) were used to determine the ecological effects of the
      mixture toxicity in the floodplain soil. None of the indices indicated direct
      effects of heavy metals on the nematode community. This can be explained by the
      high adsorption of heavy metals on organic matter and clay particles resulting in
      a low bioavailability, and questions the estimation of the toxicity based on
      total concentrations of heavy metals in such environments. The nematode fauna
      showed great seasonal variation, which most probably was related to the temporal
      inundation of the floodplain.

PMID- 18715626
TI  - Manufactured nanoparticles: an overview of their chemistry, interactions and
      potential environmental implications.
AB  - The industrial scale production and wide variety of applications of manufactured
      nanoparticles (NPs) and their possible release in considerable amounts into the
      natural aquatic environment have produced an increasing concern among the
      nanotechnology and environmental science community. In order to address this
      issue, it is important to understand NP chemistry, preparation, reactivity and
      possible mechanisms involved in their interaction with the naturally occurring
      aquatic components, particularly natural colloids and NPs present in the aquatic
      systems. In this review, an overview of the chemistry of both manufactured and
      natural aquatic NPs is outlined. This review discusses the physico-chemical
      aspects of both type of NPs as an essential point to assess possible routes
      involved in manufactured NP fate in the natural aquatic environment and their
      toxicity. Key advances related to the characterisation of the manufactured NPs
      and natural colloids.

PMID- 18715627
TI  - Improved coverage of fungal diversity in polluted groundwaters by semi-nested
      PCR.
AB  - Traditional methods used for studying communities of aquatic hyphomycetes are
      based on the detection and identification of their asexual spores under a
      microscope. These techniques limit detection to aquatic fungi present in
      sufficient quantity and capable of sporulating under laboratory conditions. Our
      objective was to develop a molecular approach to detect and monitor all types of
      fungi (i.e. strictly or facultatively aquatic) in harsh habitats (i.e.
      groundwater wells and heavily polluted surface water) where fungal biomass may
      become limited. We developed a semi-nested PCR protocol for fungal 18S ribosomal
      RNA genes coupled to subsequent analysis of the PCR products by Temperature
      Gradient Gel Electrophoresis (TGGE) to monitor the fungal community structure in
      aquatic habitats characterized by a pollution gradient. Our TGGE-protocol was
      compared with the traditional morphological approach and revealed a higher
      diversity in groundwaters and in some polluted surface waters. Thus, PCR-TGGE is
      a promising alternative in particular in habitats with low fungal biomass. The
      dynamics of fungal biomass and sporulation rates during the first weeks of leaf
      colonization showed that habitats with adverse ecological conditions allow only
      reduced fungal growth, which might subsequently impact upper trophic levels and
      thus interfere with key ecological processes of leaf decomposition.

PMID- 18715628
TI  - Modelling of radon concentration peaks in thermal spas: application to
      Polichnitos and Eftalou spas (Lesvos Island--Greece).
AB  - A mathematical model was developed for the description of radon concentration
      peaks observed in thermal spas. Modelling was based on a pragmatic mix of
      estimation and measurement of involved physical parameters. The model utilised
      non-linear first order derivative mass balance differential equations. The
      equations were described and solved numerically by the use of specially developed
      computer codes. To apply and check the model, measurements were performed in two
      thermal spas in Greece (Polichnitos and Eftalou-Lesvos Island). Forty different
      measurement sets were collected to estimate the concentration variations of
      indoor-outdoor radon, radon in the entering thermal water, the ventilation rate,
      the bathtub surface and the bath volume. Turbulence and diffusive phenomena
      involved in radon concentration variations were attributed to a time varying
      contact interfacial area (equivalent area). This area was approximated with the
      use of a mathematical function. Other model parameters were estimated from the
      literature. Through numerical solving and use of non-linear statistics, the time
      variations of the equivalent area were estimated for every measurement set.
      Computationally applied non-linear uncertainty analysis showed less sensitive
      variations of the coefficients of the equivalent area compared to parameters of
      the model. Modelled and measured radon concentration peaks were compared by the
      use of three statistical criteria for the goodness-of-fit. All the investigated
      peaks exhibited low error probability (***p<0.001) for all criteria. It was
      concluded that the present modelling achieved to predict the measured radon
      concentration peaks. Through adequate selection of model parameters the model may
      be applied to other thermal spas.

PMID- 18715629
TI  - Biomonitoring of genotoxicity using micronuclei assay in native population of
      Astyanax jacuhiensis (Characiformes: Characidae) at sites under petrochemical
      influence.
AB  - Bom Jardim brook is a small stream that flows through an area under the influence
      of a Petrochemical Complex, demanding control over its quality, so a genotoxic
      evaluation was performed. This study was conducted in situ, based on previous
      analysis on the same subject. These were performed both in vitro, with Salmonella
      typhimurium and human lymphocytes, and in vivo, using bioassays with fish exposed
      to water from the study area. The purpose of this research was to assess the
      quality of the aquatic environment and possible effects from petrochemical
      pollution to surrounding native populations. Micronuclei (MNE) and nuclear
      abnormalities (NA) frequencies in peripheral blood of Astyanax jacuhiensis, a
      native fish species collected from the study area, were used as biomarkers. Study
      period was from summer/99 to spring/2001, using samples obtained seasonally at
      two ponds upstream from the industrial area (BJN and BJPa) and two sites in Bom
      Jardim brook (BJ002 and BJ000), which are subject to Complex influence. MNE and
      NA frequencies found in individuals from BJ002 and BJ000 were similar, showing
      positive genotoxic responses related to control sites BJN and BJPa. No
      differential sensitivity could be verified for micronuclei induction between
      genders of A. jacuhiensis in the studied population. This study showed that sites
      subject to petrochemical influence were under higher genotoxic impact. Biomarkers
      adequacy to the case and the sensitivity of A. jacuhiensis for water monitoring
      could be also inferred.

PMID- 18715631
TI  - Rare variant of bladder exstrophy associated with urethral, bladder, and colonic
      duplication.
AB  - Urethral duplication, bladder duplication, and bladder exstrophy are rare
      congenital urinary tract anomalies. We present an extremely rare case of complete
      urethral and bladder duplication in a boy with bladder exstrophy, omphalocele,
      and colonic duplication. Bladder augmentation was subsequently performed using
      the left exstrophic bladder as a patch to augment the right duplicated bladder.

PMID- 18715632
TI  - Intra-thoracic cytoreduction of stage IV peritoneal malignancy: a case series.
AB  - BACKGROUND: Women with ovarian cancer primarily present with advanced intra
      abdominal disease, frequently involving the diaphragm. CASES: We present 2 cases
      of combined planned intra-thoracic and abdominopelvic radical cytoreduction for
      stage IV peritoneal malignancy. CONCLUSIONS: Our case report indicates the
      importance of a multi-disciplinary approach in treating patients with advanced
      stage peritoneal disease. Multi-disciplinary surgical procedures can achieve
      optimal cytoreduction and possibly improve overall survival.

PMID- 18715633
TI  - Brief report: Peer attachment in adolescents.

PMID- 18715634
TI  - Care at first-level facilities for children with severe pneumonia in Bangladesh:
      a cohort study.
AB  - BACKGROUND: Guidelines on integrated management of childhood illness (IMCI) for
      severe pneumonia recommend referral to hospitals. However, in many settings,
      children who are referred do not actually attend hospital, which severely limits
      appropriate care. We aimed to assess the safety and effectiveness of modified
      guidelines that allowed most children with severe pneumonia to be treated locally
      in first-level facilities, with referral only for those with danger signs or
      other severe classifications. METHODS: We did an observational cohort study in
      ten first-level health facilities in Matlab, rural Bangladesh that had
      implemented IMCI guidelines. We assessed children with severe pneumonia who were
      aged between 2 and 59 months, and for whom we could obtain complete information,
      in two cohorts: 261 children who presented to these facilities between May, 2003,
      and April, 2004 (before implementation of the modified guidelines) and 1271
      children between September, 2004, and August, 2005 (after full implementation).
      We obtained information about the characteristics and management of their
      illness, including referrals and admissions to hospital, from facility records.
      Staff visited households to obtain details of treatment, socioeconomic
      information, and final outcome, including mortality data. FINDINGS: 245 (94%) of
      261 children who had severe pneumonia were referred to hospital before the
      guidelines were modified, compared with 107 (8%) of 1271 after implementation
      (p<0.0001). 94 (36%) children with severe pneumonia received correct management
      before the guidelines were modified, compared with 1145 (90%) children after
      implementation (p<0.0001). Before modification of the guidelines, three children
      with severe pneumonia who presented at first-level facilities died, with a case
      fatality rate of 1.1%; after modification, seven children died, with a case
      fatality rate of 0.6% (p=0.39). INTERPRETATION: Local adaptation of the IMCI
      guidelines, with appropriate training and supervision, could allow safe and
      effective management of severe pneumonia, especially if compliance with referral
      is difficult because of geographic, financial, or cultural barriers.

PMID- 18715635
TI  - Childhood pneumonia deaths: a new role for health workers?

PMID- 18715636
TI  - Self-assembled biodegradable micellar nanoparticles of amphiphilic and cationic
      block copolymer for siRNA delivery.
AB  - A novel amphiphilic and cationic triblock copolymer consisting of monomethoxy
      poly(ethylene glycol), poly(epsilon-caprolactone) (PCL) and poly(2-aminoethyl
      ethylene phosphate) denoted as mPEG(45)-b-PCL(100)-b-PPEEA(12) was designed and
      synthesized for siRNA delivery. The copolymers were well characterized by (1)H
      NMR spectroscopy and gel permeation chromatography. Micelle nanoparticles' (MNPs)
      formation of this amphiphilic copolymer in aqueous solution was studied by
      dynamic light scattering, transmission electron microscopy and fluorescence
      technique. MNPs took uniform spherical morphology with zeta potential of around
      45 mV and were stabilized by hydrophobic-hydrophobic interaction in the PCL core,
      exhibiting the critical micelle concentration at 2.7 x 10(-3) mg/mL. Such MNPs
      allowed siRNA loading post nanoparticle formation without change in uniformity.
      The average diameter of nanoparticles after siRNA binding ranged from 98 to 125
      nm depending on N/P ratios. The siRNA loaded nanoparticles can be effectively
      internalized and subsequently release siRNA in HEK293 cells, resulting in
      significant gene knockdown activities, which was demonstrated by delivering two
      siRNAs targeting green fluorescence protein (GFP). It effectively silenced GFP
      expression in 40-70% GFP-expressed HEK293 cells and it was observed that higher
      N/P ratio resulted in more effective silence which was likely due to better cell
      internalization at higher N/P ratio. MTT assay demonstrated that neither MNPs
      themselves nor siRNA loaded MNPs showed cytotoxicity even at high concentrations.
      Such cationic MNPs made from biocompatible and biodegradable polymers are
      promising for siRNA delivery.

PMID- 18715637
TI  - Electrospun biomimetic nanocomposite nanofibers of hydroxyapatite/chitosan for
      bone tissue engineering.
AB  - The development of bioinspired or biomimetic materials is essential and has
      formed one of the most important paradigms in today's tissue engineering
      research. This paper reports a novel biomimetic nanocomposite nanofibers of
      hydroxyapatite/chitosan (HAp/CTS) prepared by combining an in situ co
      precipitation synthesis approach with an electrospinning process. A model HAp/CTS
      nanocomposite with the HAp mass ratio of 30 wt% was synthesized through the co
      precipitation method so as to attain homogenous dispersion of the spindle-shaped
      HAp nanoparticles (ca. 100 x 30 nm) within the chitosan matrix. By using a small
      amount (10 wt%) of ultrahigh molecular weight poly(ethylene oxide) (UHMWPEO) as a
      fiber-forming facilitating additive, continuous HAp/CTS nanofibers with a
      diameters of 214+/-25 nm had been produced successfully and the HAp nanoparticles
      with some aggregations were incorporated into the electrospun nanofibers. Further
      SAED and XRD analysis confirmed that the crystalline nature of HAp remains and
      had survived the acetic acid-dominant solvent system. Biological in vitro cell
      culture with human fetal osteoblast (hFOB) cells for up to 15 days demonstrated
      that the incorporation of HAp nanoparticles into chitosan nanofibrous scaffolds
      led to significant bone formation oriented outcomes compared to that of the pure
      electrospun CTS scaffolds. The electrospun nanocomposite nanofibers of HAp/CTS,
      with compositional and structural features close to the natural mineralized
      nanofibril counterparts, are of potential interest for bone tissue engineering
      applications.

PMID- 18715638
TI  - Bioactive, luminescent and mesoporous europium-doped hydroxyapatite as a drug
      carrier.
AB  - Bioactive, luminescent and mesoporous europium-doped hydroxyapatite (Eu:HAp) was
      successfully prepared through a simple one-step route using cationic surfactant
      as template. The obtained multifunctional hydroxyapatite was performed as a drug
      delivery carrier to investigate the drug storage/release properties using
      ibuprofen (IBU) as a model drug. The structural, morphological, textural and
      optical properties were well characterized by X-ray diffraction (XRD), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), X-ray
      photoelectron spectra (XPS), Fourier transform infrared spectroscopy (FT-IR),
      N(2) adsorption/desorption, and photoluminescence (PL) spectra, respectively. The
      results reveal that the multifunctional hydroxyapatites exhibit the typical
      ordered characteristics of the hexagonal mesostructure, and have rod-like
      morphology with the particle size of 20-40 nm in width and 100-200 nm in length.
      The drug storage/release test indicates that the luminescent HAp shows much
      similar drug loading amount and cumulative release rate to those of pure HAp.
      Interestingly, the IBU-loaded samples still show red luminescence of Eu(3+)
      ((5)D(0)-(7)F(1),(2)) under UV irradiation, and the emission intensities of
      Eu(3+) in the drug carrier system vary with the released amount of IBU, thus
      making the drug release be easily tracked and monitored by the change of the
      luminescence intensity.

PMID- 18715639
TI  - The behavior of aged regenerated Bombyx mori silk fibroin solutions studied by
      (1)H NMR and rheology.
AB  - As part of a project to utilize the regenerated silk fibroin (RSF) membranes as a
      supporting matrix for the attachment and growth of corneal stem/progenitor cells
      in the development of tissue engineered constructs for the surgical restoration
      of the ocular surface, the behavior of the aged RSF solutions has been
      investigated. The solutions were produced from domesticated silkworm (Bombyx
      mori) cocoons according to a protocol involving successive dissolution steps,
      filtration and dialysis. The solutions were kept at 4 degrees C in a refrigerator
      for a certain period of time until near the gelation time. The changes in
      molecular conformation were studied by solution-state (1)H NMR, while the flow of
      the solutions was characterized by rheological method. Upon ageing turbidity
      developed in solutions and the viscosity continuously decreased prior to a
      drastic increased near the gelation time. The (1)H resonances of aged solutions
      showed a consistent downfield shift as compared to the (1)H resonances of the
      fresh solution. Shear thinning with anomalous short recovery within a certain
      range of low shear rates occurred in both fresh and aged solutions. While the
      solutions behave as pseudo-plastic materials, the chain conformation in aged
      solutions adopted all secondary configurations with beta-strand being
      predominant.

PMID- 18715640
TI  - Spatial and temporal expression of tachykinins and NK1- and NK2-receptor gene
      during TNB induced colitis in rats.
AB  - The distribution and modification of the tachykinins Substance P (SP) and
      neurokinin A (NKA), their precursor beta-preprotachykinins (beta-PPT) and the
      receptors involved in their activity, NK-1 and NK-2, were studied in
      trinitrobenzensulphonic acid (TNB) colitis. Rats were intrarectally treated with
      a 120 mg/ml of TNB solution and sacrificed at various times after colitis
      induction. During the acute phases of colitis, a marked decrease in tissue SP and
      NKA levels were observed along with an increased transcription of beta-PPT mRNA
      in the neurons of the myenteric plexus and an increased myeloperoxidase activity,
      which is an index of the tissue's inflammatory status. De novo expression of both
      NK(1) and NK(2) receptor mRNA was observed during the acute phase of TNB-colitis
      in mesenchymal cells around dilated submucosal vessels but their expression in
      smooth muscle cells of the muscularis mucosae and propria was moderately down
      regulated. The peptide levels, myeloperoxidase activity and gene expression of
      tachykinin receptors were then restored during the late phases (2-4 weeks after
      the apten administration) while beta-PPT mRNA remained highly expressed in the
      myenteric plexus ganglia showing that SP and NKA are involved in repair
      processes. These results point to the enhanced release of tachykinins during the
      initial phase of colitis and a restoration of this neuropeptide pool in the
      healing of the tissue.

PMID- 18715641
TI  - Cough mixture abuse, folate deficiency and acute lymphoblastic leukemia.

PMID- 18715642
TI  - Circulating heat shock protein 70 and progression in patients with chronic
      myeloid leukemia.
AB  - We evaluated the association of circulating levels of heat shock protein 70
      (Hsp70) in plasma with clinical behavior and progression in 139 chronic myeloid
      leukemia (CML) patients. Circulating Hsp70 levels did not differ significantly
      between CML patients in the chronic phase (n=93; median 33.24 ng/mL, range 3.89
      128.2 ng/mL) and those in the accelerated/blast phase (n=46; median 26.57 ng/mL,
      range 4.5-114.7 ng/mL). However, overall CML patients had significantly higher
      levels of Hsp70 than healthy subjects (n=95, median 4.17 ng/mL, range 1.75-24.7
      ng/mL) (P<0.001). In chronic phase CML patients, Hsp70 levels above the median
      were associated with a higher rate of progression to the accelerated/blast phase
      and a tendency toward shorter survival. Plasma Hsp70 thus could be a potential
      marker for predicting disease progression in patients with chronic phase CML.

PMID- 18715643
TI  - Ascorbic acid combats arsenic-induced oxidative stress in mice liver.
AB  - Repeated injections of arsenic trioxide induced oxidative stress and
      hepatotoxicity in mice as revealed from elevated levels of glutamate oxaloacetate
      transaminases, glutamate pyruvate transaminases, acid and alkaline phosphatases,
      lipid peroxidation along with reduction of superoxide dismutase, catalase,
      reduced glutathione content, glutathione reductase and succinate dehydrogenase
      activities. The present investigation was undertaken to test whether simultaneous
      feeding of vitamin C can combat hepatotoxicity in arsenic intoxicated mice.
      Hepatoprotective potential of vitamin C was indicated by its ability to restore
      GSH, SOD, CAT, AcP, AlkP and GRD levels towards near normal. Electron microscopic
      studies further supported the biochemical findings confirming the
      hepatoprotective potential of ascorbic acid. Besides, cytogenetical endpoints
      (chromosome aberrations, micronuclei, mitotic index and sperm head anomaly) were
      also analyzed. Administration of vitamin C alone did not show any sign of
      toxicity of its own. Based on the present findings, ascorbic acid appears to have
      protective effects against arsenic toxicity and oxidative stress.

PMID- 18715644
TI  - Role of clay content in partitioning, uptake and toxicity of zinc in the
      earthworm Eisenia fetida.
AB  - We studied the effect of clay content on the bioavailability of zinc to pre
      clitellate earthworm, Eisenia fetida in the laboratory using OECD artificial soil
      adjusted to 5%, 20%, and 40% clay. Batches of worms were exposed to a wide range
      of zinc concentrations. Mortality, growth, maturation (% clitellate), cocoon
      production, and body zinc concentrations were assessed over and after a period of
      4 weeks. Total, DTPA, and CaCl(2) extractable zinc in the substrates were also
      determined. The results of the biological responses showed that interaction of
      clay and zinc had a significant influence on mortality but not on the other
      biological parameters. None of the three extraction methods showed consistent and
      significant effect of clay content on zinc partitioning. Although total, DTPA,
      and CaCl(2) extracts of zinc correlated strongly with one another and were in
      similar relation with the observed biological responses, only the CaCl(2) extract
      revealed a time dependent availability of this metal. It is concluded that clay
      content had no significant influence on sub-lethal toxicity of zinc to this
      earthworm over the range of exposure concentrations.

PMID- 18715645
TI  - Humoral immune responsiveness to a defined epitope on factor VIII before and
      after B cell ablation with rituximab.
AB  - In hemophilia A, up to 30% of patients develop neutralizing antibodies
      (inhibitors) to factor VIII (FVIII). Treatment of an inhibitor patient with anti
      CD20 (rituximab) provided an opportunity to study the humoral immune response to
      the well defined and constantly administered antigen, FVIII, before therapy and
      after B cell repopulation. Levels of CD20(+) B cells, inhibitor titers as well as
      antibody titers to selected antigens and FVIII-specific IgG subclasses were
      monitored. Inhibitors were absent for 420 days after B cell depletion, whereas
      antibody titers to other monitored antigens remained constant. No changes of
      FVIII specific IgG subclass distribution were observed. In order to characterize
      specific epitopes phage displayed random peptide libraries were screened with
      plasma before treatment and after recurrence of inhibitors. A peptide
      corresponding to a dominant amino acid motif selected by phage display bound
      FVIII-specific IgG1 before and after anti-CD20 treatment and partially restored
      FVIII activity in vitro. This peptide mimics a conformational epitope in the A2
      domain of factor VIII, which is still recognized after inhibitor relapse despite
      complete B cell depletion and long-term absence of inhibitors. Mapping of
      specific epitopes on a defined antigen gives further information on mechanisms
      underlying B cell repopulation after rituximab therapy.

PMID- 18715646
TI  - Structural basis and functional effects of the interaction between complement
      inhibitor C4b-binding protein and DNA.
AB  - Human C4b-binding protein (C4BP) is a soluble, multiple-subunit inhibitor of
      complement that circulates in blood. Recently C4BP was shown to bind DNA, reduce
      DNA release from necrotic cells and limit DNA-mediated complement activation in
      solution. Herein we employed nuclear magnetic resonance spectroscopy to measure
      chemical shift perturbations and used them to restrain the computational docking
      of a B-form 10-base-pair DNA molecule onto the solution structure of C4BP alpha
      chain complement control protein (CCP) domains 1-2 (C4BP12). Six amino acid
      residues located on one face of the interdomain junction - Val(38), Ser(40),
      Thr(43), Tyr(62), Lys(63) and Arg(64) - exhibited the largest chemical shift
      changes. In the model, the DNA lies in a cleft formed by the interdomain
      interface. The double-helix is perpendicular to the long axis of C4BP12
      consistent with the multiple arms of C4BP binding to adjacent sites on a longer
      DNA molecule. The DNA lies in a region previously shown to bind C4b and heparin
      and these molecules (but not C3b) inhibited the DNA-C4BP interaction.
      Nonetheless, crucial C4BP functions such as cofactor activity for factor I
      cleavage of C4b and C3b, and decay acceleration of the classical C3 convertase
      appeared not to be affected by the presence of DNA. Taken together these results
      reinforce the case for the occupation of some of the seven arms of C4BP in a
      multivalent interaction with DNA or surface bound glycosaminoglycans while other
      arms engage C4b or C3b.

PMID- 18715647
TI  - Developmental and epigenetic regulation of the human TLR3 gene.
AB  - The receptor encoded by the human TLR3 gene recognizes double-strand RNAs
      (dsRNAs) associated with viral infection. TLR3 expression is strongly activated
      upon differentiation of monocytes to dendritic cells, and can be further
      stimulated by the dsRNA analog polyinosine:polycytosine (PI:C). We report
      evidence for developmental regulation of the TLR3 gene. In dendritic cells
      derived from cord blood, both differentiation- and PI:C-associated TLR3
      transcriptional activation are impaired as compared to cells from adults.
      Consistent with relative expression patterns, chromatin states and remodeling
      differ between newborn and adult samples. TLR3 expression in newborn dendritic
      cells exhibits heterocellularity and allelic imbalance (skewing), features
      characteristic of cis-acting epigenetic control. These findings reveal a new
      source for variability in innate immune system function and provide a model for
      further study of perinatal epigenetic transitions during development.

PMID- 18715648
TI  - Native hip joint septic arthritis in 20 adults: delayed presentation beyond three
      weeks predicts need for excision arthroplasty.
AB  - OBJECTIVES: Septic arthritis of native hip joints is an uncommon condition in
      adults in Western Europe, but continues to present a challenge to medical and
      surgical management. We set out to study the natural history and bacteriology of
      the disease in this group, with a particular focus on patients requiring excision
      arthroplasty (EA). METHODS: We retrospectively studied 26 secondary referral
      cases (20 adults) managed by a specialist bone infection unit over a 12 year
      period. RESULTS: Our patient cohort was diverse, affecting all age groups in the
      presence and absence of co-morbid conditions. The commonest pathogen was
      Staphylococcus aureus. Of 20 adults studied, five (25%) required EA. Symptom
      duration prior to presentation was a statistical predictor of the requirement for
      EA (p<0.003); in particular, symptom duration of over three weeks was strongly
      associated with requirement for this procedure (p<0.0003). CONCLUSIONS: In cases
      that present promptly, combined surgical drainage and intravenous antibiotics
      should be expected to eradicate infection and to salvage the femoral head. Cases
      presenting following a delay are more likely to require EA and subsequent hip
      reconstruction.

PMID- 18715649
TI  - Efficacy of linezolid alone and in combination with rifampin in staphylococcal
      experimental foreign-body infection.
AB  - OBJECTIVES: The knowledge about efficacy of linezolid alone or in combination
      with rifampin in device infections is limited. We test their in vitro and in vivo
      efficacy in a rat model of foreign-body infection by methicillin-susceptible S.
      aureus. METHODS: In vitro studies for logarithmic and stationary bacteria were
      performed. In vivo efficacy (decrease in bacterial counts in tissue cage fluid)
      was evaluated at: (i) after 7-day therapy (groups: linezolid, cloxacillin,
      rifampin, linezolid-rifampin and cloxacillin-rifampin); and (ii) after 10-day
      therapy (groups: rifampin and linezolid-rifampin). RESULTS: After 7-day therapy
      all groups were significantly better than controls; linezolid (Delta log cfu/ml: 
      0.59, no resistant strains) and cloxacillin (-0.85) were the least effective
      therapy; linezolid was significantly less active (P<0.05) than rifampin (-1.22,
      resistance 90%), cloxacillin-rifampin (-1.3) and linezolid-rifampin (-1.14).
      After 10-day therapy linezolid-rifampin was the most effective treatment (Delta
      log -1.44, no resistance, P<0.05); in contrast, rifampin resulted ineffective
      (Delta log 0.1) due to the growth of resistant strains (100%). CONCLUSIONS:
      Linezolid alone showed moderate efficacy, whereas its combination with rifampin
      prevented the emergence of rifampin resistance. The efficacy of linezolid
      rifampin combination was initially similar to that of rifampin alone, but in
      contrast to rifampin, it increased over time revealing the impact of protection
      against rifampin resistance and the benefits of rifampin activity.

PMID- 18715650
TI  - Disseminated salmonellosis in a patient treated with temozolomide.
AB  - Temozolomide is a relatively new chemotherapeutic agent frequently associated
      with selective CD4+ T-lymphocytopenia. Patients with cell-mediated immune defects
      are at higher risk for acquiring infections with Salmonella species. We describe
      the first case of disseminated salmonellosis in a patient treated with
      temozolomide.

PMID- 18715651
TI  - Psychosocial functioning among bipolar youth.
AB  - BACKGROUND: Evidence indicates that children and adolescents with bipolar
      disorder (BP) experience significant functional impairment. However, little is
      known about the association between psychosocial functioning and episodes of
      illness, demographic, and clinical variables in this population. METHODS:
      Subjects included 446 patients aged 7 to 17 diagnosed with DSM-IV bipolar
      disorder via the K-SADS for the Course and Outcome of Bipolar Youth (COBY) study.
      The Psychosocial Functioning Schedule of the Adolescent Longitudinal Interval
      Follow-Up Assessment (A-LIFE) was administered at study intake. RESULTS: Mild to
      moderate levels of psychosocial impairment were evident in work (includes
      academics), interpersonal, and overall domains of functioning among BP youth.
      Multivariate analyses indicated that the strongest predictors of psychosocial
      impairment were adolescence (regardless of age of onset), current mood episode,
      current affective symptom severity, current psychotic symptoms, and current
      comorbid conduct disorder. Bipolar youth in-episode were significantly more
      impaired than those in partial remission/recovery in every functional domain
      examined and were less satisfied with their functioning. Yet, BP youth in partial
      remission/recovery reported significant psychosocial impairment. LIMITATIONS:
      Limitations include the reliance on patient and parent retrospective report of
      psychosocial functioning. Additionally, we did not account for the impact of
      psychosocial and pharmacological interventions on functioning. CONCLUSIONS:
      Findings suggest pediatric BP is associated with significant impairment in
      psychosocial functioning during and between episodes, with greater impairment
      during mood episodes than during partial remission/recovery. Additionally,
      functional impairment in BP appears to increase during adolescence regardless of
      age of onset. Clinicians should carefully assess and address psychosocial
      impairment during and between mood episodes, with particular attention to the
      functioning of BP adolescents.

PMID- 18715652
TI  - Heat shock protein-containing exosomes in mid-trimester amniotic fluids.
AB  - Exosomes are multivesicular bodies formed by inverse membrane budding into the
      lumen of an endocytic compartment. Fusion with the plasma membrane leads to their
      release into the external milieu. The incorporation of heat shock proteins into
      exosomes has been associated with immune regulatory activity. We have examined
      whether heat shock protein-containing exosomes are present in mid-trimester
      amniotic fluid. Exosomes were isolated from mid-trimester amniotic fluids by
      sequential low-speed and high-speed centrifugation followed by sucrose density
      gradient centrifugation. Biochemical characterization included floatation pattern
      in sucrose gradients, acetylcholinesterase (AChE) activity and Western blot
      analysis for exosome-containing proteins. Exosomes were present in each of 23
      amniotic fluids tested. They banded at a density of 1.17g/ml in sucrose
      gradients, were positive for AChE activity and contained tubulin, the inducible
      72kDa heat shock protein, Hsp72 and the constitutively expressed heat shock
      protein, Hsc73; they were negative for calnexin. Exosome concentrations
      correlated positively with the number of pregnancies. Heat shock protein
      containing exosomes are constituents of mid-trimester amniotic fluids and may
      contribute to immune regulation within the amniotic cavity.

PMID- 18715654
TI  - Can sociodemographic and clinical variables predict the quality of life of
      outpatients with major depression?
AB  - Quality of life (QOL) in depression could be of great value as an outcome
      measure, especially in determining the effectiveness of treatment strategies.
      However, for this aim to be accomplished, it is important to clarify the
      relationship between QOL and a number of potentially mediating factors, such as
      sociodemographic and clinical variables. For this purpose, we assessed 140
      depressed outpatients with the Mini International Neuropsychiatric Interview, the
      WHOQOL BREF, and the Beck Depression Inventory (BDI). After standard and stepwise
      multiple regression analyses, the following variables were found to be
      independent predictors of QOL: BDI score for the physical (adjusted R(2)=0.125)
      and psychological (adjusted R(2)=0.23) domains, and for the overall QOL estimate
      (adjusted R(2)=0.226); age, suicidality according to the MINI and BDI score for
      the social relations domain (adjusted R(2)=0.244); and ethnicity, psychiatric
      comorbidity, psychotic symptoms and BDI score for the environmental domain
      (adjusted R(2)=0.328). Limitations of the study include its cross-sectional
      design, relatively small sample size, and lack of objective measures of
      depressive symptomatology. Sociodemographic and clinical variables appear to
      explain less than 32.8% of the variance of QOL in subjects with depressive
      disorders. Clearly, further studies are needed to clarify which additional
      factors play a role in determining QOL in major depression.

PMID- 18715653
TI  - Deficits in docosahexaenoic acid and associated elevations in the metabolism of
      arachidonic acid and saturated fatty acids in the postmortem orbitofrontal cortex
      of patients with bipolar disorder.
AB  - Previous antemortem and postmortem tissue fatty acid composition studies have
      observed significant deficits in the omega-3 fatty acid docosahexaenoic acid
      (DHA, 22:6n-3) in red blood cell (RBC) and postmortem cortical membranes of
      patients with unipolar depression. In the present study, we determined the fatty
      acid composition of postmortem orbitofrontal cortex (OFC, Brodmann area 10) of
      patients with bipolar disorder (n=18) and age-matched normal controls (n=19) by
      gas chromatography. After correction for multiple comparisons, DHA (-24%),
      arachidonic acid (-14%), and stearic acid (C18:0) (-4.5%) compositions were
      significantly lower, and cis-vaccenic acid (18:1n-7) (+12.5%) composition
      significantly higher, in the OFC of bipolar patients relative to normal controls.
      Based on metabolite:precursor ratios, significant elevations in arachidonic acid,
      stearic acid, and palmitic acid conversion/metabolism were observed in the OFC of
      bipolar patients, and were inversely correlated with DHA composition. Deficits in
      OFC DHA and arachidonic acid composition, and elevations in arachidonic acid
      metabolism, were numerically (but not significantly) greater in drug-free bipolar
      patients relative to patients treated with mood-stabilizer or antipsychotic
      medications. OFC DHA and arachidonic acid deficits were greater in patients plus
      normal controls with high vs. low alcohol abuse severity. These results add to a
      growing body of evidence implicating omega-3 fatty acid deficiency as well as the
      OFC in the pathoaetiology of bipolar disorder.

PMID- 18715655
TI  - Bacterial cell wall products increases stabilization of HIF-1 alpha in an
      oligodendrocyte cell line preconditioned by cobalt chloride or desferrioxamine.
AB  - We examined the effect of lipopolysaccharide (LPS) or lipotechoic acid (LTA) on
      the regulation of hypoxia inducible factor (HIF-1) alpha on the MO3.13 cells, a
      human oligodendroglial cell line. Our study shows that MO3.13 cells express the
      toll like receptors (TLR's) but do not increase cellular levels of HIF-1 alpha
      following exposure to bacterial cell wall products. When MO3.13 cells were
      preconditioned by desferrioxamine (DFO) or cobalt chloride (CoCl(2)) and then
      treated with either LPS or LTA, HIF-1 alpha levels were higher than that induced
      by DFO or CoCl(2) alone. The increase in HIF-1 alpha was due to increased protein
      stability that was mediated by activation of the ERK-MAP kinase pathway.

PMID- 18715656
TI  - Beneficial effects of statin treatment after myocardial infarction: Is progenitor
      cell mobilization the missing link?
AB  - It is widely accepted that statin treatment improves survival in patients with
      myocardial infarction. Evidence also suggests that aggressive statin treatment is
      superior than standard dose during the post-infarction period. However, the exact
      mechanisms are still not well understood. Endothelial progenitor cells (EPC) play
      a key role in vascular homeostasis, since they contribute to the repair of
      damaged endothelium post-myocardial infarction, while they induce
      neoangiogenesis. Recent evidence suggests that statins may exert their beneficial
      effect in patients with recent myocardial infarction, by inducing EPC
      mobilization, and this may be a key mechanism by which statins improve survival
      in these patients. However, large scale clinical trials remain to prove that
      aggressive statin treatment is superior than standard dose in these patients, by
      inducing a more effective EPC mobilization.

PMID- 18715657
TI  - Myocardial infarction related to aberrant left circumflex artery.
AB  - We present a case of lateral wall infarction in the territory of an anomalous
      circumflex artery without significant stenosis. The unusual location of the
      infarction suggests a causal relation with the anomalous artery through minor
      plaque rupture, which may have resulted from mechanical stress.

PMID- 18715658
TI  - A broken heart: a stretch too far: an overview of mouse models with mutations in
      stretch-sensor components.
AB  - With every heartbeat the heart must contract and relax. This seemingly trivial
      process critically needs tight control of contraction and relaxation phases, and
      extremely efficient coordination between these two phases to control blood flow
      and maintain cardiac homeostasis. To achieve this, specialized sensors are
      required to detect the inherent repeatedly changing environment and needs. One
      sensor is a stretch-sensor that monitors the filling of the ventricles. Its
      molecular identity and localization are only partly understood. Here we give a
      synopsis of the genetic models that leap into our understanding of stretch
      sensors. We focus on the widely acknowledged sarcomeric sensor at the Z-disc and
      the costamere sensor at the sarcolemma. Recently, several novel components of
      both sensors were discovered. Given that these two sensors seem physically
      connected, it is likely that these two models are not mutually exclusive and
      might even communicate. We describe briefly how candidate and known proteins
      within these sensors receive and transduce mechanical signals in the
      cardiomyocyte that lead to changes in gene expression underlying homeostasis and
      its restoration in the heart. Emphasis is placed on the putative link between
      altered stretch-sensor function and heart failure observed in different genetic
      mouse models of stretch-sensor components.

PMID- 18715659
TI  - Long term follow up after percutaneous closure of PFO in 357 patients with
      paradoxical embolism: Difference in occlusion systems and influence of atrial
      septum aneurysm.
AB  - BACKGROUND: Percutaneous transcatheter closure of patent foramen ovale (PFO) in
      cryptogenic stroke or TIA is an alternative to medical therapy especially in
      patients with atrial septal aneurysm (ASA). The differences in time to complete
      occlusion for various closure devices in PFO alone and PFO plus ASA are of
      natural interest. METHODS AND RESULTS: Between January, 1st 1998 and November,
      30th 2006 percutaneous PFO closure was performed in 357 patients with a history
      of > or =1 paradoxical embolism using three different devices: Amplatzer PFO
      (n=199), Starflex-(n=48) and Helex Occluder (n=110). All patients were assigned
      to a post-interventional protocol with contrast-enhanced transesophageal
      echocardiography (TOE) at 1 and 6 months and every 6 to 12 months in case of
      incomplete closure. Definite closure was confirmed in at least two consecutive
      TOE studies. The closure time curves between the three devices were significantly
      different (p=0.0072). Devices of 25 mm or less had a better occlusion rate. The
      difference between the closure time curves of PFO and PFO+ASA concerning each
      device type was significant for Helex (p=0.006) and Starflex (p=0.030). In regard
      to the occlusion time for large devices Helex succeeded later than Amplatzer and
      Starflex (p=0.0029). Concerning the cumulative follow up period of 1265 patient
      years the recurrence/re-event rate of cerebral and peripheral thromboembolic
      events was 0.7% per patient year. No relation to residual PFO shunting or to
      thrombus formation was seen. There were no peri-interventional technical
      complications. In five patients of the Starflex group thrombi were detected in
      the four week TOE controls. CONCLUSION: The closure rate is dependent on occluder
      size and type plus the occurrence of an atrial septum aneurysm.

PMID- 18715660
TI  - The endocannabinoid system and cardiometabolic risk: effects of CB1 receptor
      blockade on lipid metabolism.
AB  - Cardiometabolic risk factors affect more than 47 million adults in the United
      States today. Although certain risk factors (e.g., obesity, dyslipidemia,
      hypertension, and hyperglycemia) contribute independently to the global risk,
      dyslipidemia is one of the most important risk factors for cardiovascular
      disease. Successful treatment requires a well-coordinated multifaceted approach,
      with commitment to a long-term program for disease management. Although initial
      attempts should focus on dietary changes and increased physical activity, most
      patients also need effective, safe, and well-monitored pharmacotherapy.
      Experimental studies have shown that overactivation of the endocannabinoid system
      a physiologic signaling system involved in regulating energy intake, fatty acid
      synthesis and storage, and glucose and lipid metabolism-is associated with
      obesity, dyslipidemia, and insulin resistance. In clinical trials, selective
      blockade of CB1 receptors has resulted in substantial weight loss and significant
      improvement in lipid profiles. The effects of rimonabant, the first selective CB1
      receptor blocker, were evaluated in 6600 obese or overweight adults who
      participated in one of 4 multicenter, placebo-controlled, randomized clinical
      trials for at least 1 year. Significant improvement in lipid profiles
      (specifically HDL and triglyceride levels and ratio of total cholesterol to HDL
      cholesterol) was seen in the 2503 patients taking rimonabant 20 mg/day,
      independent of its substantial effects on weight loss. No significant changes in
      LDL or total cholesterol were observed. Results of clinical trials with
      rimonabant are promising. Additional long-term controlled studies with
      appropriate follow-up are warranted to confirm the clinical potential of this
      drug, particularly its effects on dyslipidemia and other cardiovascular
      endpoints.

PMID- 18715661
TI  - Acute myocardial infarction and transient ischemic attack in a patient with lone
      atrial fibrillation and normal coronary arteries.
AB  - We present the case of a 50-year old female with a history of paroxysmal atrial
      fibrillation and without any antithrombotic therapy, who was admitted to the
      neurologic department of our hospital with symptoms of cerebral ischemia. Two
      hours after the release of the neurological syndrome, she experienced an acute ST
      segment elevation myocardial infarction (STEMI) of the inferior wall, which was
      not thrombolysed due to active menstruation. The coronary angiography was
      performed nine days later and it showed normal coronary arteries. This is the
      first case report of a TIA and an acute myocardial infarction due to atrial
      emboli, in a middle aged woman without any coronary lesions. In our opinion it
      points out the strength and the effectiveness of the internal fibrinolytic
      mechanisms.

PMID- 18715662
TI  - A cross-sectional study of Salmonella in pre-slaughter pigs in a production
      compartment of northern Thailand.
AB  - A cross-sectional study was conducted to determine the prevalence of Salmonella
      and to associate management factors in fattening pigs in a production compartment
      of northern Thailand. A total of 194 fecal samples and 166 environmental samples
      were collected from 22 fattening pig herds for isolation and identification of
      Salmonella. An additional 427 serum samples were collected from the same herds to
      determine Salmonella antibodies using ELISA. A questionnaire was used to collect
      management factors likely to be associated with Salmonella identification.
      Prevalence of Salmonella in each sample and its confidence interval was adjusted
      for clustering by herds using linearization technique. A generalized estimating
      equation was used to determine the odds ratio and significance level for each
      management factor in a logistic regression model. Salmonella was found in all 22
      study pig herds with a fecal sample prevalence of 63% (95%CI: 56-69%) and a serum
      sample prevalence of 72%. However, isolation results were not significantly
      different from ELISA results. The most isolated serotype was Salmonella Rissen
      (49%) followed by Salmonella Typhimurium (19%), Salmonella Stanley (12%) and
      Salmonella Weltevreden (4%) being significantly different in the different
      specimens collected (p=.024). The final logistic regression model with isolation
      results as outcome showed that medium herd size (OR=2.32, p=0.003), quality
      certification according to the Department of Livestock Development standard
      (OR=1.88, p=0.000), use of effective microorganisms (OR=1.51, p=0.022), slurry
      waste management (OR=2.17, p=0.000) and less number of pigs per pen (OR=1.12,
      p=0.000) were significantly associated with positive Salmonella isolation; with
      positive ELISA results, however, only the use of effective microorganisms was
      significantly associated (OR=2.63, p=0.011).

PMID- 18715663
TI  - Simulation of climate-change scenarios to explain Usutu-virus dynamics in
      Austria.
AB  - The emergence and spread of infectious diseases in mid-latitudes, so far mainly
      observed in the tropics, considerably increase under the current situation of
      climate change. A recent example is the Usutu virus (USUV) outbreak in Austria.
      USUV is closely related to the West Nile virus in the U.S. and caused mass
      mortalities mainly of blackbirds (Turdus merula). The USUV flavivirus persists in
      a natural transmission cycle between vectors (mosquitoes) and host reservoirs
      (birds) and leads - once endemic in a population - to periodic outbreaks. In an
      epidemic model to explain the USUV dynamics in Austria 2001-2005, USUV dynamics
      were mainly determined by an interaction of bird immunity and environmental
      temperature. To investigate future scenarios, we entered temperature predictions
      from five global climate models into the USUV model and also considered four
      different climate-warming scenarios defined by the I ntergovernmental Panel on
      Climate Change, IPCC (20 different model-scenario combinations). We downscaled
      the 20 time series of predicted temperatures (through the year 2100) to represent
      the region around Vienna. Our simulations predict that USUV will persist in the
      host population after the epidemic peak observed in 2003. USUV-specific annual
      blackbird-mortality time series predict that the outbreak frequency increases
      successively from the beginning to the end of the century. Simulations of worst
      case scenarios result in an endemic equilibrium with a decline of the blackbird
      population of about 24%. Additionally we calculated the annually averaged basic
      reproduction number for the period 1901-2100. The latter depict that undetected
      major outbreaks before 2000 were unlikely, whereas it is likely that the USUV
      becomes endemic after 2040.

PMID- 18715664
TI  - Increased serum pigment epithelium derived factor levels in Type 2 diabetes
      patients.
AB  - Serum PEDF levels (mean (S.D.)) were increased in 96 Type 2 diabetic vs. 54 non
      diabetic subjects; 5.3 (2.8) vs. 3.2 (2.0)mug/ml, p<0.001. In diabetes, PEDF
      correlated with BMI, serum creatinine and LDL-cholesterol, but not with other
      lipids, HbA1c or CRP. PEDF did not differ by drugs, complications, or gender.

PMID- 18715665
TI  - Treatment predictors of a sustained virologic response in hepatitis B and C.
AB  - Treatment predictors are important tools for the management of therapy in
      patients with chronic hepatitis B and C virus (HBV, HCV) infection. In chronic
      hepatitis B, several pretreatment parameters have been identified for prediction
      of virologic response to interferon alfa-based antiviral therapies or treatment
      with polymerase inhibitors. In interferon alfa and pegylated interferon alfa
      treated patients, low baseline HBV DNA concentrations, HBV genotype A (B), and
      high baseline ALT levels are significantly associated with treatment response. In
      patients treated with nucleos(t)ide analogues, low baseline HBV DNA but not viral
      genotype is positively associated with virologic response. During treatment the
      best predictor of response is HBV DNA kinetics. Early viral suppression is
      associated with favourable virologic response and reduced risk for subsequent
      resistance mutations. For the current standard treatment with pegylated
      interferon alfa and ribavirin in patients with chronic hepatitis C, infection
      with HCV genotypes 2 and 3, baseline viral load below 400,000-800,000 IU/ml,
      Asian and Caucasian ethnicity, younger age, low GGT levels, absence of advanced
      fibrosis/cirrhosis, and absence of steatosis in the liver have been identified as
      independent pretreatment predictors of a sustained virologic response. After
      initiation of treatment, initial viral decline with undetectable HCV-RNA at week
      4 of therapy (RVR) is the best predictor of sustained virologic response
      independent of HCV genotype.

PMID- 18715666
TI  - Statements from the Taormina expert meeting on occult hepatitis B virus
      infection.

PMID- 18715668
TI  - Pregnancy and sexual function in liver transplantation.

PMID- 18715669
TI  - Which physicians have access to electronic prescribing and which ones end up
      using it?
AB  - OBJECTIVES: This study examines the availability of electronic prescription and
      the utilization of e-prescribing by physicians in the US. METHODS: Nationally
      representative data from the 2004-2005 Community Tracking Study Physician Survey
      were used to identify which subgroups of physicians have access to e-prescribing
      technology and which subgroups are using this technology more or less
      intensively. Exhaustive Chi-squared Automatic Interaction Detection (CHAID) was
      employed for statistical data segmentation. RESULTS: Results indicate that the
      rapidly increasing adoption of electronic prescription is diminished by
      relatively low physician utilization. E-prescription utilization was segmented
      among practice size and type. There were also differences in e-prescription use
      by age, gender, and ethnicity/race in some subgroups. Actual use of e
      prescription was very low for female physicians in surgical specialties,
      psychiatry, and obstetrics/gynecology, and for Hispanic physicians in pediatrics,
      internal medicine, and family/general practice in solo/two physician practices,
      medical schools, and hospitals. CONCLUSIONS: Insights from segmentation analyses
      could be used to identify adoption barriers and to develop targeted interventions
      to accelerate the implementation of e-prescription systems in physician
      practices.

PMID- 18715670
TI  - A decision support system for suggesting ventilator settings: retrospective
      evaluation in cardiac surgery patients ventilated in the ICU.
AB  - Selecting appropriate ventilator settings decreases the risk of ventilator
      induced lung injury. A decision support system (DSS) has been developed based on
      physiological models, which can advise on setting of tidal volume (Vt),
      respiratory frequency (f) and fraction of inspired oxygen (FiO2). The aim of this
      study is to assess the feasibility of the DSS by comparing its advice with the
      values used in clinical practice. Data from 20 patients following uncomplicated
      coronary artery bypass grafting (CABG) with cardiopulmonary bypass was used to
      test the DSS. Ventilator settings suggested by the DSS were compared to the
      settings selected by the clinician. When compared to the clinician the DSS
      suggested: lowering FiO2 (by median 7%, range 2-17%) at high SpO2 and increasing
      FiO2 (by median 2%, range 1-5%) at low SpO2; lowering ventilation volume (by
      median 0.57 l min(-1), range 0.2-1.1 l min(-1)) at high pHa and increasing
      ventilation volume (by median 0.4 l min(-1), range 0.1-0.9 l min(-1)) at low pHa.
      Suggested changes in ventilation volume were such that simulated values of PIP
      were < or = 22.9 cmH2O and respiratory frequency < or = 18 breaths min(-1). In
      all cases, computer suggested values of FiO2, Vt or f were consistent with
      maintaining sufficient oxygenation, normalising pH and obtaining low values of
      PIP.

PMID- 18715671
TI  - Capturing escape in infectious disease dynamics.
AB  - Identifying the causes of interannual variability in disease dynamics is
      important for understanding and managing epidemics. Traditionally, these causes
      have been classified as intrinsic (e.g. immunity fluctuations) or extrinsic (e.g.
      climate forcing); ecologists determine the relative contributions of these
      factors by applying statistical models to time series of cases. Here we address
      the problem of isolating the drivers of pathogen dynamics that are influenced by
      antigenic evolution. Recent findings indicate that many pathogens escape immunity
      in a punctuated manner; for them, we argue that time series of cases alone will
      be insufficient to isolate causal drivers. We detail observations that can reveal
      the presence of punctuated immune escape, and which can be used in new
      statistical approaches to identify extrinsic and intrinsic regulators of disease.

PMID- 18715672
TI  - Stress hormones and mate choice.
AB  - A few recent studies have suggested that glucocorticoid stress hormones can play
      a role in sexual selection. In terms of mate choice, these studies have shown
      that individuals can exhibit preferences for mates with either low baseline or
      peak glucocorticoid levels. This appears to occur because stress hormones can be
      key mediators of many condition-dependent, sexually selected traits that serve as
      honest signals of mate quality. We suggest that our understanding of how sexual
      selection can influence the glucocorticoid stress response will be expanded by
      studying the interactions among glucocorticoid stress hormones, sex steroids and
      body condition.

PMID- 18715674
TI  - Tasmanian devil facial tumour disease: lessons for conservation biology.
AB  - Tasmanian devil facial tumour disease is an infectious cancer that threatens the
      largest surviving marsupial carnivore with extinction. After emerging in 1996, it
      has spread across most of the range of the species, leading to a population
      decline of more than 60%. This bizarre disease, in which the cancer cells
      themselves are the infective agent, illustrates some important general principles
      about disease and conservation biology, including the threat posed by loss of
      genetic diversity and the potential of pathogens with frequency-dependent
      transmission to cause extinction.

PMID- 18715673
TI  - Origins and evolution of eukaryotic RNA interference.
AB  - Small interfering RNAs (siRNAs) and genome-encoded microRNAs (miRNAs) silence
      genes via complementary interactions with mRNAs. With thousands of miRNA genes
      identified and genome sequences of diverse eukaryotes available for comparison,
      the opportunity emerges for insights into the origin and evolution of RNA
      interference (RNAi). The miRNA repertoires of plants and animals appear to have
      evolved independently. However, conservation of the key proteins involved in RNAi
      suggests that the last common ancestor of modern eukaryotes possessed siRNA-based
      mechanisms. Prokaryotes have an RNAi-like defense system that is functionally
      analogous but not homologous to eukaryotic RNAi. The protein machinery of
      eukaryotic RNAi seems to have been pieced together from ancestral archaeal,
      bacterial and phage proteins that are involved in DNA repair and RNA processing.

PMID- 18715675
TI  - Evolution, museums and society.
AB  - Visitors to natural history museums have an incomplete understanding of
      evolution. Although they are relatively knowledgeable about fossils and
      geological time, they have a poor understanding of natural selection. Museums in
      the 21st century can effectively increase public understanding of evolution
      through interactive displays, novel content (e.g. genomics), engaging videos and
      cyberexhibits that communicate to a broad spectrum of society, both within the
      exhibit halls as well as outside the museum.

PMID- 18715676
TI  - Age-related changes in cortical swallowing processing.
AB  - The cortical organization of swallowing has been mainly studied in young and
      healthy subjects. Aging effects on human deglutition have been found in several
      behavioral studies and are known to affect both the oral and pharyngeal phases of
      swallowing. The aim of this study was to evaluate a potential cortical
      compensation of age-related swallowing impairment. Whole-head MEG was employed in
      9 healthy elderly subjects (mean age 71.6 years) and compared to 9 healthy young
      participants (mean age 23.8 years). Data were analyzed by means of time-frequency
      plots and synthetic aperture magnetometry (SAM). Group analysis of individual SAM
      data was performed using a permutation test. The main finding of this study was
      an increase of somatosensory cortical activation during swallowing execution in
      elderly subjects compared to the young control group. This effect was present in
      both hemispheres. These results point to adaptive cerebral changes in response to
      aging effects on the complex process of swallowing. Our finding underlines the
      relevance of age matched control groups in neuroimaging studies related to
      deglutition or other complex sensorimotor processes.

PMID- 18715677
TI  - Cell-produced alpha-synuclein oligomers are targeted to, and impair, the 26S
      proteasome.
AB  - Proteasomal dysfunction may play a role in neurodegenerative conditions and
      protein aggregation. Overexpression in neuronal cells of alpha-synuclein, a
      molecule linked to Parkinson's Disease, may lead to proteasomal dysfunction.
      Using PC12 cells stably expressing wild-type or mutant alpha-synuclein and gel
      filtration, we demonstrate that soluble, intermediate size oligomers of alpha
      synuclein co-elute with the 26S proteasome. These soluble oligomers associate
      with the 26S proteasome and are significantly increased following treatment with
      proteasomal, but not lysosomal, inhibitors, indicating specific degradation of
      these particular species by the 26S proteasome. Importantly, expression of alpha
      synuclein resulted in a significant inhibition of all proteasomal activities
      without affecting the levels or assembly of the 26S proteasome. Pharmacological
      dissociation of alpha-synuclein oligomers restored proteasomal function and
      reduced polyubiquitinated protein load in intact cells. Our findings suggest a
      model where only a subset of specific soluble cell-derived alpha-synuclein
      oligomers is targeted to the 26S proteasome for degradation, and simultaneously
      inhibit its function, likely by impeding access of other proteasomal substrates.

PMID- 18715679
TI  - Synthesis, spectral studies and in vitro antibacterial activity of steroidal
      thiosemicarbazone and their palladium (Pd (II)) complexes.
AB  - We investigated the antibacterial activity of some new steroidal
      thiosemicarbazone and their Pd(II) metal complexes. Metal complexes were prepared
      from the reaction of steroidal thiosemicarbazone with [Pd(DMSO)(2)Cl(2)].
      Coordination via the thionic sulphur and the azomethine nitrogen atom of the
      thiosemicarbazone to the metal ion, the thiosemicarbazone derivatives were
      obtained by the thiosemicarbazide with steroidal ketones. All the compounds have
      been confirmed by spectral data. The antibacterial activity of these compounds
      was first tested in vitro by the disk diffusion assay against two gram-positive
      and two gram-negative bacteria, and then the minimum inhibitory concentration
      (MIC) was determined. The results showed that steroidal complexes are better
      inhibit growth as compared to steroidal thiosemicarbazones of both types of the
      bacteria (gram-positive and gram-negative); compound Ia is better antibacterial
      agent as compared to amoxicillin.

PMID- 18715678
TI  - Age-related changes in glial cells of dopamine midbrain subregions in rhesus
      monkeys.
AB  - Aging remains the strongest risk factor for developing Parkinson's disease (PD),
      and there is selective vulnerability in midbrain dopamine (DA) neuron
      degeneration in PD. By tracking normal aging-related changes with an emphasis on
      regional specificity, factors involved in selective vulnerability and resistance
      to degeneration can be studied. Towards this end, we sought to determine whether
      age-related changes in microglia and astrocytes in rhesus monkeys are region
      specific, suggestive of involvement in regional differences in vulnerability to
      degeneration that may be relevant to PD pathogenesis. Gliosis in midbrain DA
      subregions was measured by estimating glia number using unbiased stereology,
      assessing fluorescence intensity for proteins upregulated during activation, and
      rating morphology. With normal aging, microglia exhibited increased staining
      intensity and a shift to more activated morphologies preferentially in the
      vulnerable substantia nigra-ventral tier (vtSN). Astrocytes did not exhibit age
      related changes consistent with an involvement in regional vulnerability in any
      measure. Our results suggest advancing age is associated with chronic mild
      inflammation in the vtSN, which may render these DA neurons more vulnerable to
      degeneration.

PMID- 18715680
TI  - Synthesis, antibacterial and anticonvulsant evaluations of some cyclic
      enaminones.
AB  - Several cyclic enaminone esters were synthesized, characterized, and evaluated
      for anticonvulsant and antibacterial activities using standardized tests. A
      series of enaminones were mainly phenyl analogs of anticonvulsant enaminones,
      while a second series comprised of compounds bearing the oxazolidinone
      pharmacophoric moiety found in the synthetic antibacterial linezolid. The
      enaminone ester bearing an unsubstituted anilino analog showed class 2
      anticonvulsant activity. This represents a first report of an unsubstituted
      anilino enaminone with anticonvulsant activity. The enaminone esters gave
      interesting UV data, and four analogs displayed potent anticonvulsant activities,
      while another four compounds showed moderate anticonvulsant activities.
      Surprisingly, none of the enaminone esters had any significant antibacterial
      activity.

PMID- 18715681
TI  - Association of metabolic syndrome with cognitive function: the role of sex and
      age.
AB  - BACKGROUND & AIMS: Cognitive impairment is a prevalent condition in older
      populations, independently associated with disability and mortality. Some studies
      have suggested a negative correlation between metabolic syndrome (MetS) and
      cognitive functioning, but results in older subjects are controversial. The aim
      of this study was to evaluate the association of cognitive performance with MetS
      in an older unselected population. METHODS: We evaluated the association of the
      Hodkinson Abbreviated Mental Test (AMT) score with MetS, as defined by the
      National Cholesterol Education Program's ATP-III criteria, in all 353 subjects
      aged 75+ living in Tuscania (Italy). RESULTS: MetS was positively associated with
      the AMT score in multivariable linear regression analysis, after adjusting
      (B=0.45, 95% CI=0.04-0.90; p=0.03). When the same regression model was analyzed
      after stratifying for sex, such an association was significant in women (B=0.76,
      95% CI=0.16-1.36; p=0.01), but not in men. Also, when the regression model was
      analyzed in women, MetS was associated with better cognition (B=1.41, 95% CI=0.51
      2.30; p<0.01) among participants aged 80+. CONCLUSIONS: MetS is associated with
      better cognitive performance in community-dwelling elderly; such an association
      seems to depend upon the oldest female subjects.

PMID- 18715682
TI  - Clinical relationships tested by iatrogenicity: the case of haemophiliac patients
      faced with the epidemic of transfusional AIDS.
AB  - After being victims of a serious iatrogenous damage, what kind of relationship
      can patients rebuild with the world of medicine? In this article, I examine this
      question in terms of the contaminated blood affair in France. Using a qualitative
      study of haemophiliac patients and their families as a base, I looked at the
      changes in their modes of commitment to medicine, from the period preceding
      contamination with AIDS through blood transfusion, until the present day. It
      would seem that the experience of iatrogenous injustice was at the root of a
      major reconfiguration: all of the patients looked back over their trajectories,
      examined their relationship with the medical world and changed their positions,
      but without necessarily drawing the same conclusions or taking the same stances.
      This article looks at the change from relationships essentially based on
      cooperation to relationships that are more negotiated. It also shows the current
      diversity in forms of commitment: they are the fruit of critical work, carried
      out by patients and their families, which reassesses both the cognitive and moral
      bases of medical legitimacy. The analysis of the reconfiguration of the
      relationships that haemophiliac patients have had with the medical world in the
      aftermath of the contaminated blood affair is enlightening in two ways. First of
      all, the current medical world would appear to be deeply marked by health
      scandals and the victims have become prime actors. Secondly, the experience of
      iatrogenicity asks, with especial acuteness, the question of confidence that is
      at the core of any clinical relationship. It thus has a heuristic value of
      general scope.

PMID- 18715683
TI  - Does implicit learning in non-demented Parkinson's disease depend on the level of
      cognitive functioning?
AB  - We investigated the influence of the level of cognitive functioning on sequence
      specific learning in Parkinson's disease (PD). This was done by examining the
      relationship between the scales for outcomes in Parkinson's disease-cognition
      [SCOPA-COG, Marinus, J., Visser, M., Verwey, N. A., Verhey, F. R. J., Middelkoop,
      H. A. M.,Stiggelbout, A., et al. (2003). Assessment of cognition in Parkinson's
      disease. Neurology, 61, 1222-1228] and the serial reaction time (SRT) task
      [Nissen, M. J., & Bullemer, P. T. (1987). Attentional requirements for learning:
      Evidence from performance measures. Cognitive Psychology, 19, 1-32] in a
      homogeneous sample, consisting of 25 PD patients diagnosed in Stage 3 of the
      Hoehn and Yahr [Hoehn, M. M., & Yahr, M. D. (1967). Parkinsonism: onset,
      progression, and mortality. Neurology, 17, 427-442] scale. Six patients in the
      low scoring cognitive group, 11 patients in the average scoring and eight
      patients in the high scoring group, conducted a SRT task with a deterministic
      sequence. Sequence-specific learning was assessed by inserting a random block to
      determine whether the acquisition of sequence movements differed between groups.
      Our results indicate an association between cognitive functioning in PD patients
      and sequence learning. These findings emphasize the use of assessing cognition in
      addition to the well-known motor aspects in PD.

PMID- 18715684
TI  - No evidence for object alternation impairment in obsessive-compulsive disorder
      (OCD).
AB  - Recent neuroimaging studies have consistently ascribed the orbito-frontal cortex
      (OFC) a pivotal role in the pathogenesis of obsessive-compulsive disorder (OCD).
      Cognitive tests presumed sensitive to this region, such as the Object Alternation
      Task (OAT), are considered important tools to verify this assumption and to
      investigate the impact of cortical dysfunction on behavior. The aim of the
      present study was to assess if patients with OCD show enhanced perseveration
      errors on the OAT relative to healthy controls taking into account several
      potential moderators, especially comorbid depression and OCD subtype. Thirty-five
      OCD patients and 18 healthy controls underwent the OAT as well as the Trail
      Making Tests (TMT) A and B. In line with prior studies, OCD patients were slowed
      on both TMT tasks. In contrast, samples performed similarly on the OAT. While the
      latter finding does not invalidate the assumption that the OFC is affected in
      OCD, dysfunctions involving this region may be more subtle than often claimed and
      likely encompass only a small subset of functional domains hosted in the OFC.

PMID- 18715685
TI  - Thermally induced changes in the structure and activity of yeast hexokinase B.
AB  - Yeast hexokinase has been poorly characterized in regard with its stability. In
      the present study, various spectroscopic techniques were employed to investigate
      thermal stability of the monomeric form of yeast hexokinase B (YHB). The enzyme
      underwent a conformational transition with a T(m) of about 41.9 degrees C. The
      structural transition proved to be significantly reversible below 55 degrees C
      and irreversible at higher temperatures. Thermoinactivation studies revealed that
      enzymatic activity diminished significantly at high temperatures, with greater
      loss of activity observed above 55 degrees C. Release of ammonia upon deamidation
      of YHB obeyed a similar temperature-dependence pattern. Dynamic light scattering
      and size exclusion-HPLC indicated formation of stable aggregates. Taking various
      findings on the influence of osmolytes and chaperone-like agents on YHB thermal
      denaturation together, it is proposed that the purely conformational transition
      of YHB is reversible, and irreversibility is due to aggregation, as a major
      cause. Deamidation of a critical Asn or Gln residue(s) may also play an important
      role.

PMID- 18715686
TI  - MHC expression kinetics and immunogenicity of mesenchymal stromal cells after
      short-term IFN-gamma challenge.
AB  - OBJECTIVE: Under the influence of interferon-gamma (IFN-gamma), mesenchymal
      stromal cells (MSCs) are conditional antigen-presenting cells, which have
      immunosuppressive potential. Apart from IFN-gamma upregulation of major
      histocompatibility complexes class I and II (MHC-I and MHC-II) expression, the
      underlying kinetics and mechanisms have not been described previously. This
      information is helpful to delineate how human MSCs can be modulated by IFN-gamma
      in different clinical scenarios. MATERIALS AND METHODS: Here, we demonstrated
      that IFN-gamma-treated MSCs underwent classical signal transduction pathway via
      phosphorylation of signal transducers and activators of transcription-1,
      activation of interferon regulatory factor-1, and class II transactivator
      comparable to that of primary human blood macrophages. RESULTS: IFN-gamma
      markedly induced expression of MHC-I instantly, while its effects on MHC-II were
      less dramatic and delayed up to 4 days. This is due to a slower intracellular
      transport of the MHC-II antigen to the membrane surface. More important is that
      MSCs showed a reduction in their proliferation by 50% without evidence of cell
      death after prolonged IFN-gamma treatment for 8 days. High-dose IFN-gamma-treated
      MSCs (500 U/mL) could initiate T-cell activation as indicated by expression of
      CD25 and proliferation of allogeneic T cells. CONCLUSIONS: The summative IFN
      gamma effects will adversely affect the immunoprivilege status and lifespan of
      MSCs.

PMID- 18715687
TI  - Allogeneic bone marrow transplantation restores liver function in Fah-knockout
      mice.
AB  - OBJECTIVE: In murine models, transplantation of wild-type bone marrow cells (BMC)
      can counterbalance genetic liver defects by fusion between transplanted marrow
      cells and resident hepatocytes. This phenomenon, however, is of no immediate
      clinical use because all syngeneic BMC harbor the same underlying genetic defect.
      MATERIALS AND METHODS: Describing the fusion between transplanted allogeneic BMC
      and resident hepatocytes in a murine model of hereditary tyrosinemia type I
      (fumarylacetoacetate hydrolase [Fah] knockout mouse), we transplanted BMC from
      fully allogeneic BALB/c donors into Fah(-/-) recipients after lethal total body
      irradiation. RESULTS: Following hematopoietic reconstitution, recipients remained
      healthy without pharmacological support (withdrawal of 2-2-nitro-4
      fluoromethylbenzoyl-1,3-cyclohexanedione [NTBC]). Metabolic serum parameters
      improved nearly to wild-type levels. Livers of recipient animals contained up to
      10% functional hepatocytes that stained positive for wild-type Fah, as well as
      both donor and recipient major histocompatibility complex. Flow cytometry
      confirmed this coexpression on a single cell level. Application of T-cell
      depleted bone marrow reduced onset of early graft-vs-host disease. CONCLUSIONS:
      We introduce the observation that allogeneic bone marrow transplantation can lead
      to stable cell fusion of BMC with recipient hepatocytes and restored liver
      function in a model of otherwise lethal genetic liver disease. Thus, in
      principle, allogeneic cell fusion can be a possible management of hereditary
      liver diseases. Long-term immunological properties of fusion cells have to be
      further investigated.

PMID- 18715688
TI  - Compartmentalization of allogeneic T-cell responses in the bone marrow and spleen
      of humanized NOD/SCID mice containing activated human resident myeloid dendritic
      cells.
AB  - OBJECTIVE: Human allogeneic (allo)-T-cell responses within recipient lymphoid
      tissues and the degree to which they are altered in the presence of activated
      tissue-resident dendritic cells (DC) remain unknown. This study examined allo-T
      cell recruitment and the early allo-T-cell responses that occur in the bone
      marrow (BM) and spleen (SP) of humanized (hu) nonobese diabetic (NOD)/severe
      combined immunodeficient (SCID) recipients containing activated human tissue
      resident myeloid DC (MDC). MATERIALS AND METHODS: Human naive allo-T cells were
      transferred into polyinosinic:polycytidylic acid [poly(I:C)]-treated or untreated
      huNOD/SCID recipients containing human tissue-resident DC derived from
      transplanted CD34(+) cells. Activation of human tissue-resident MDC mediated by
      poly(I:C) treatment, recruitment, proliferation, and effector differentiation of
      allo-T cells in the BM and SP of huNOD/SCID recipients were analyzed in vivo by
      flow cytometry. RESULTS: Poly(I:C) treatment induced transient activation of
      human MDC within a maximum of 8 hours, as evidenced in the BM by an increased
      proportion of MDC-expressing CD86 while in the SP by MDC expressing CD86 and
      producing interleukin-12. Poly(I:C)-pretreated huNOD/SCID recipients showed
      changes in the recruitment of allo-T cells in the BM and SP and developed
      different allo-T cell responses within the BM and SP compartments. In the BM,
      allo-T cells underwent multiple divisions and increased numbers of interferon
      gamma(+) and tumor necrosis factor-alpha(+) effector cells, while the majority of
      splenic allo-T cells underwent a single division and had fewer effector allo-T
      cells. CONCLUSIONS: Our experimental transplantation model demonstrates that
      early allo-T-cell responses are regulated by compartmentalization in the BM and
      secondary lymphoid tissues; events potentially occurring after
      allotransplantation in human recipients.

PMID- 18715689
TI  - Establishment and characterization of a new human acute myelocytic leukemia cell
      line SH-2 with a loss of Y chromosome, a derivative chromosome 16 resulting from
      an unbalanced translocation between chromosomes 16 and 17, monosomy 17, trisomy
      19, and p53 alteration.
AB  - OBJECTIVE: To report here a new acute myelocytic leukemia (AML) cell line SH-2
      and describe its biological characteristics. MATERIALS AND METHODS: Mononuclear
      cells isolated from a patient with AML-M2 subtype were passaged by liquid culture
      medium. Interleukin-3 and bone marrow stromal cells were used to support cell
      proliferation at the first 3 months. Various methods, including cytogenetic
      analysis, fluorescence in situ hybridization (FISH), multiplex FISH (M-FISH),
      reverse transcriptase polymerase chain reaction (RT-PCR), multiplex RT-PCR, short
      tandem repeat (STR)-PCR, direct sequencing of DNA, clonogenic assay, and
      tumorigenicity in nude and severe combined immunodeficient (SCID) mice were
      employed to identify and characterize SH-2 cell line. RESULTS: SH-2 cells were
      maintained without cytokine and stromal cells for 3 years. It had no Epstein-Barr
      virus or mycoplasma contamination. The SH-2 cell line showed typical myelocytic
      features in morphology and simultaneous strongly expressed myeloid antigens
      (CD13, 99.6% and CD33, 99.26%) and natural killer (NK)-related antigens (CD56,
      99.5% and CD16/56, 99.62%) suggesting that SH-2 is an AML cell line with NK
      antigen expression. SH-2 cell line initially showed a karyotype of 45, X, -Y,
      der(16)t(16;17)(q24;q12), -17, +19. During the passage period, the cells with a
      hypodiploid karyotype gradually decreased and were replaced by the near
      tetraploid cells with a karyotype of 71-105(86), XX, -Y, -Y, der(16)t(16;17)x2, 
      17, -17, +19, +19. FISH and M-FISH delineated all abnormalities. SH-2 cells had
      the approximately same morphological, immunophenotypical, and cytogenetic
      features as the patient's leukemia cells had. STR-PCR provided powerful evidence
      for the derivation of SH-2 cell line from the patient's leukemia cells. SH-2
      cells showed multiple drug resistance (MDR), which may be related to the p53 gene
      alteration, including the loss of one p53 allele due to the monosomy 17 and a
      point mutation of CAG to CAT at codon 576 of exon 5 in another p53 allele
      resulting in the loss of p53 gene function. In addition, SH-2 cell line did not
      express MDR-related genes, such as MDR1, multidrug resistance-related protein,
      and lung resistance protein, but expressed apoptosis-related genes, such as Bcl
      2, Fas, glutathione S-transferase-pi, and p21, which were also related to the
      MDR. SH-2 cell line had tumorigenic capacities in nude and SCID mice. CONCLUSION:
      Because SH-2 cell line had a clear biology background, it will provide a useful
      tool for the study of the pathogenesis and treatment strategy of AML with MDR.

PMID- 18715690
TI  - Gene therapy of Diamond Blackfan anemia CD34(+) cells leads to improved erythroid
      development and engraftment following transplantation.
AB  - OBJECTIVE: Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia
      caused by mutations in ribosomal protein (RP) genes. Our aim is to develop gene
      therapy for DBA patients with mutations in RPS19. We previously demonstrated that
      RPS19 gene transfer partially corrects erythroid development in vitro. In this
      study, we asked if RPS19 gene transfer corrects erythroid development in unsorted
      cells transplanted to immunodeficient mice and if the RPS19-corrected fraction
      has a proliferative advantage after transplantation. We further determined if
      high level of RPS19 expression is required for correction. MATERIAL AND METHODS:
      Mobilized peripheral blood CD34(+) cells were transduced by oncoretroviral vector
      particles pseudotyped with the feline endogenous retrovirus envelope. Vectors
      containing two different promoters with different RPS19 transgene expression
      levels were compared. Transduced cells were transplanted to immunocompromised
      nonobese diabetic/severe combined immunodeficient-beta2 microglobulin null mice
      in order to assess therapeutic effects of RPS19 gene transfer in vivo. RESULTS:
      We show that correction of erythroid development requires high RPS19 expression.
      The corrected fraction of unselected DBA cells have a survival advantage in vivo,
      suggesting that successful gene therapy may only require correction of a fraction
      of the patient cells. CONCLUSION: Our findings are fundamental for development of
      clinical gene therapy for DBA because they demonstrate increased engraftment of
      RPS19-transduced cells without selection of gene-corrected cells prior to
      transplantation, an essential prelude to studying long-term therapeutic effects
      in emerging animal models for DBA.

PMID- 18715691
TI  - JTA-009, a fully human antibody against human AILIM/ICOS, ameliorates graft-vs
      host reaction in SCID mice grafted with human PBMCs.
AB  - OBJECTIVE: Activation-inducible lymphocyte immunomediatory molecule (AILIM; also
      referred to as inducible costimulator [ICOS]) is the third molecule identified in
      the CD28 family participating in T-cell activation. AILIM/ICOS has been
      implicated in both effector and pathogenic T-cell functions, as evidenced by the
      beneficial effects of AILIM/ICOS blockade in several murine disease models. In
      the present study, the role of human AILIM/ICOS in T-cell function was
      investigated using a fully human monoclonal antibody specific to human AILIM/ICOS
      (JTA-009). MATERIALS AND METHODS: The effect of JTA-009 on allogenic T-cell
      proliferation was examined using human mixed lymphocyte reaction (MLR). To
      investigate the efficacy of AILIM/ICOS blockade in vivo, a graft-vs-host disease
      (GVHD) model, in which severe combined immunodeficient (SCID) mice were grafted
      with human peripheral blood mononuclear cells (PBMCs), was used. RESULTS: In MLR,
      suppressive effect of JTA-009 on allogenic T-cell proliferation was detected with
      comparable potency to CD28 blockade by cytotoxic T-lymphocyte antigen 4 (CTLA4)
      Ig at an intermediate culture phase. JTA-009 acts as a blocking antibody in vivo
      and inhibited binding of human AILIM/ICOS to mouse AILIM/ICOS ligand (B7h).
      Treatment with JTA-009 significantly prolonged survival of mice, with reductions
      of human interferon-gamma levels in blood and number of human cells in spleens.
      CONCLUSION: These results demonstrate that human AILIM/ICOS plays a role in the
      GVHD pathogenesis mediated by human T cells, and its blockade is attractive for
      abrogating undesired T-cell responses as is well-documented in mice.

PMID- 18715692
TI  - What is the best technique for urethroplasty?
AB  - CONTEXT: There is no clear evidence that determines which type of urethroplasty
      to perform under which particular circumstance. OBJECTIVE: To review the options
      for urethroplasty at different sites in the urethra and for different types of
      stricture indicating which procedure should be used in which circumstances
      according to the best available evidence. EVIDENCE ACQUISITION: Recent
      publications have been reviewed and supplemented with the authors' personal
      experience. EVIDENCE SYNTHESIS: Currently, in the developed world, the most
      common types of stricture are relatively short and are situated in the bulbar
      urethra. There is good evidence that these are best treated by excision and end
      to-end anastomosis if they are short enough or by patch urethroplasty using a
      buccal mucosal graft if they are longer. Distal penile urethral strictures are
      the next most common type of stricture, but the evidence base is weaker, although
      there is agreement that penile strictures due to lichen sclerosus often require a
      staged approach to reconstruction, again using buccal mucosal grafts.
      Urethroplasty for pelvic fracture urethral injury is an altogether different type
      of technique for an altogether different type of pathology. There is good
      evidence that this is best treated by bulbo-prostatic anastomotic urethroplasty.
      Other types of strictures and salvage surgery have no good evidence base and are
      specialised areas where experience and judgement are necessary. CONCLUSIONS: The
      evidence base for urethral surgery has been developed for the more common types
      of urethral strictures in the last 20 yr, but it is still as much an art as it is
      a science.

PMID- 18715693
TI  - Editorial comment on: upper urinary tract urothelial cell carcinomas and other
      urological malignancies involved in the hereditary nonpolyposis colorectal cancer
      (Lynch syndrome) tumor spectrum.

PMID- 18715694
TI  - Single-incision, umbilical laparoscopic versus conventional laparoscopic
      nephrectomy: a comparison of perioperative outcomes and short-term measures of
      convalescence.
AB  - BACKGROUND: Recent reports have suggested that single-port or single-incision
      laparoscopic surgery (SILS) is technically feasible. OBJECTIVE: To present a
      comparison between SILS and conventional laparoscopic nephrectomy with respect to
      perioperative outcomes and short-term measures of convalescence. DESIGN, SETTING,
      AND PARTICIPANTS: This was a case-control study comparing 11 SILS nephrectomies
      (cases) and 22 conventional laparoscopic nephrectomies (controls) performed from
      September 2004 to April 2008. The control group was matched in a 2:1 ratio to
      SILS cases with respect to patient age, surgical indication, and tumor size.
      INTERVENTION: A single surgeon performed all SILS nephrectomy cases using three
      adjacent 5-mm trocars inserted through a single 2.5-cm periumbilical incision.
      MEASUREMENTS: Demographics, operative time, blood loss, perioperative
      complications, transfusion requirement, decrease in serum hemoglobin, analgesic
      requirement, length of stay, and final pathology were compared. RESULTS AND
      LIMITATIONS: Mean patient age was 53 yr for both groups, with more females in the
      SILS cohort (82% vs 41%). Nephrectomy was performed for benign disease in 45% of
      the cases. Median tumor size was 5.5 cm for both groups, and all but one
      suspected malignancy was renal cell carcinoma on final pathology. There was no
      difference between SILS and conventional laparoscopy cases in median operative
      time (122 min vs 125 min, p=0.78), percent decrease from preoperative hemoglobin
      (14.1% vs 15.8%, p=0.52), analgesic use (8 morphine equivalents vs 15 morphine
      equivalents, p=0.69), length of stay (49 h vs. 53 h, p=0.44), or complication
      rate (0% for both). The SILS group did have a lower recorded median estimated
      blood loss (20 ml vs 100ml, p=0.001). This study is retrospective and is
      susceptible to all limitations and biases inherent in such a design. CONCLUSIONS:
      SILS nephrectomy is feasible with perioperative outcomes and short-term measures
      of convalescence comparable to conventional laparoscopic nephrectomy. Although
      SILS may offer a subjective cosmetic advantage, prospective comparison is needed
      to more clearly define its role.

PMID- 18715695
TI  - Upper urinary tract urothelial cell carcinomas and other urological malignancies
      involved in the hereditary nonpolyposis colorectal cancer (lynch syndrome) tumor
      spectrum.
AB  - CONTEXT: The data describing the urologic extracolonic cancers associated with
      hereditary nonpolyposis colorectal cancer (HNPCC) are variable. OBJECTIVE:
      Provide an update about the current urologic tumor spectrum in HNPCC. EVIDENCE
      ACQUISITION: Data on HNPCC extracolonic tumor spectrum published in the
      literature were analysed using MEDLINE with emphasis on urological malignancies,
      upper tract tumors, clinical criteria, genetic diagnosis and counselling.
      EVIDENCE SYNTHESIS: HNPCC is a form of colorectal cancer with a dominant
      autosomal mode of inheritance. HNPCC is caused by germ-line mutations affecting
      one or several mismatch repair genes. Cancers other than colorectal cancer are
      sometimes associated with HNPCC. These include specific urological malignancies,
      most notably tumors of the upper urinary tract, which have been reported to occur
      at a rate x22 higher than the general population. Upper urinary tract tumors rank
      third (5%) after colon (63%) and endometrial (9%) cancer within the group of
      HNPCC related tumors. Prostate cancer and testicular germ cell tumors are rarely
      associated. Due to lack of appreciation of such hereditary associations, some
      inherited cancers are still misclassified as sporadic and their incidence is
      underestimated. The biological tests requested in suspected cases of HNPCC are:
      microsatellite instability (MSI) analysis, immunohistochemistry and DNA
      sequencing. When gene mutations are detected, the patient and their family will
      benefit from a multidisciplinary management approach. The presence of other HNPCC
      associated cancers is sought and close monitoring of patients is undertaken.
      Genetic counselling is provided to the patient's family. CONCLUSIONS: The
      recognized urologic tumor spectrum in HNPCC includes upper tract tumors. However,
      in order not to overlook a hereditary cancer, urologists should be aware of the
      possible urological malignancies associated with HNPCC (i.e., prostate and
      testicular carcinomas) and evaluate appropriately anyone they feel are at high
      risk of underlying HNPCC based on set clinical criteria.

PMID- 18715696
TI  - Endoscopic combined intrarenal surgery in Galdakao-modified supine Valdivia
      position: a new standard for percutaneous nephrolithotomy?
AB  - BACKGROUND: Percutaneous nephrolithotomy (PCNL), the gold standard for the
      management of large and/or complex urolithiasis, is conventionally performed with
      the patient in the prone position, which has several drawbacks. Of the various
      changes in patient positioning proposed over the years, the Galdakao-modified
      supine Valdivia (GMSV) position seems the most beneficial. It allows simultaneous
      performance of PCNL and retrograde ureteroscopy (ECIRS, Endoscopic Combined Intra
      Renal Surgery) and has unquestionable anaesthesiological advantages. OBJECTIVE:
      To prospectively analyse the safety and efficacy of endoscopic combined
      intrarenal surgery (ECIRS) in GMSV position for the treatment of large and/or
      complex urolithiasis. DESIGN, SETTING, AND PARTICIPANTS: From April 2004 to
      December 2007, 127 consecutive patients who were followed in our department for
      large and/or complex urolithiasis were selected for surgery (American Society of
      Anesthesiologists [ASA] score 1-3, no active urinary tract infection [UTI], any
      body mass index [BMI]). INTERVENTION: All the patients underwent ECIRS in GMSV
      position. Technical choices about percutaneous access, endoscopic instruments and
      accessories, and postoperative renal and ureteral drainage are detailed.
      MEASUREMENTS: Patients' mean age plus or minus standard deviation (+/- SD) was
      53.1 yr+/-14.2. Of the 127 patients, 5.5% had congenital renal abnormalities,
      3.9% had solitary kidneys, and 60.6% were symptomatic for renal colics,
      haematuria, and recurrent UTI. Mean stone size+/-SD was 23.8mm+/-7.3 (range: 11
      40); 33.8% of the calculi were calyceal, 33.1% were pelvic, 33.1% were multiple
      or staghorn, and 4.7% were also ureteral. RESULTS AND LIMITATIONS: Mean operative
      time+/-SD was 70min+/-28, including patient positioning. Stone-free rate was
      81.9% after the first treatment and was 87.4% after a second early treatment
      using the same percutaneous access during the same hospital stay (mean+/-SD: 5.1
      d+/-2.9). We registered overall complications at 38.6% with no splanchnic
      injuries or deaths and no perioperative anaesthesiological problems. CONCLUSIONS:
      ECIRS performed in GMSV position seems to be a safe, effective, and versatile
      procedure with a high one-step stone-free rate, unquestionable anaesthesiological
      advantages, and no additional procedure-related complications.

PMID- 18715698
TI  - Are antisperm antibodies really associated with proven chronic inflammatory and
      infectious diseases of the male reproductive tract?
AB  - BACKGROUND: It is debated whether chronic urogenital inflammations and infections
      may trigger the formation of antisperm antibodies (ASA) in semen. OBJECTIVE: To
      evaluate the formation of ASA in defined chronic inflammatory and infectious
      diseases of the male reproductive tract (MRT). DESIGN, SETTING, AND PARTICIPANTS:
      Three hundred sixty-five patients retrospectively enrolled in a single center
      were categorized as having National Institutes of Health (NIH) category II
      chronic prostatitis (n=38), NIH category IIIa chronic prostatitis/chronic pelvic
      pain syndrome (CP/CPPS) (n=59), NIH category IIIb CP/CPPS (n=213), chronic
      epididymitis (n=34), and chronic urethritis (n=21). Forty-five age-matched men
      served as controls. MEASUREMENTS: All subjects underwent microbiologic and
      cytologic analysis for common bacteria, yeasts, and mycoplasma using the four
      glass test. Urine samples, ejaculates, and urethral swabs were analyzed with
      polymerase chain reaction (PCR) for Chlamydia trachomatis and Neisseria
      gonorrhea. Semen analysis followed World Health Organization (WHO) standards. ASA
      in seminal plasma were analyzed using the mixed agglutination reaction (MAR)
      test. RESULTS AND LIMITATIONS: The overall positive detection rate of clinically
      significant levels (> or = 50% of spermatozoa coated by ASA) of IgG and IgA
      antibodies was 1.8% and 0.8%, respectively, in the patient group. No clinically
      significant levels of ASA were detected in the control group, and no
      statistically significant difference was observed between controls and patients
      (IgG, p=1.0; IgA, p=1.0). No difference was found between the different
      inflammatory and infectious diseases and the control group in the detection rate
      of ASA, even when the cut-point value was lowered to > or = 1% (IgG, p=0.4; IgA,
      p=0.3). Moreover, in one selected subgroup of patients (n=26) with persistent
      increased inflammatory parameters (peroxidase-positive leukocytes [PPL] > or = 1
      x 10(6)/ml and elastase > or = 230 ng/ml), no significant difference in the
      levels of ASA was observed compared with the controls (IgG, p=0.1; IgA, p=0.8).
      CONCLUSION: There is no association between chronic inflammatory or infectious
      diseases of the MRT and the presence of ASA in semen.

PMID- 18715699
TI  - Editorial comment on: Single-incision, umbilical laparoscopic versus conventional
      laparoscopic nephrectomy: a comparison of perioperative outcomes and short-term
      measures of convalescence.

PMID- 18715700
TI  - A preoperative prognostic model for patients treated with nephrectomy for renal
      cell carcinoma.
AB  - BACKGROUND: Currently two pretreatment prognostic models with limited accuracy
      (65-67%) can be used to predict survival in patients with localized renal cell
      carcinoma (RCC). OBJECTIVE: We set out to develop a more accurate pretreatment
      model for predicting RCC-specific mortality after nephrectomy for all stages of
      RCC. DESIGN, SETTING, AND PARTICIPANTS: The data originated from a series of
      prospectively recorded contemporary cases of patients treated with radical or
      partial nephrectomy between 1984 and 2006. Model development was performed using
      data from 2474 patients from five centers and external validation was performed
      using data from 1972 patients from seven centers. MEASUREMENTS: The probability
      of RCC-specific mortality was modeled using Cox regression. The significance of
      the predictors was confirmed using competing risks analyses, which account for
      mortality from other causes. RESULTS AND LIMITATIONS: Median follow-up in
      patients who did not die of RCC-specific causes was 4.2 yr and 3.5 yr in the
      development and validation cohorts, respectively. The freedom from cancer
      specific mortality rates in the nomogram development cohort were 75.4% at 5 yr
      after nephrectomy and 68.3% at 10 yr after nephrectomy. All variables except
      gender achieved independent predictor status. In the external validation cohort
      the nomogram predictions were 88.1% accurate at 1 yr, 86.8% accurate at 2 yr,
      86.8% accurate at 5 yr, and 84.2% accurate at 10 yr. CONCLUSIONS: Our model
      substantially exceeds the accuracy of the existing pretreatment models.
      Consequently, the proposed nomogram-based predictions may be used as benchmark
      data for pretreatment decision making in patients with various stages of RCC.

PMID- 18715701
TI  - Editorial comment on: Are antisperm antibodies really associated with proven
      chronic inflammatory and infectious diseases of the male reproductive tract?

PMID- 18715702
TI  - Editorial comment on: endoscopic combined intrarenal surgery in Galdakao-modified
      supine Valdivia position: a new standard for percutaneous nephrolithotomy?

PMID- 18715703
TI  - Editorial comment on: Single-incision, umbilical laparoscopic versus conventional
      laparoscopic nephrectomy: a comparison of perioperative outcomes and short-term
      measures of convalescence.

PMID- 18715704
TI  - Editorial comment on: upper urinary tract urothelial cell carcinomas and other
      urological malignancies involved in the hereditary nonpolyposis colorectal cancer
      (Lynch syndrome) tumor spectrum.

PMID- 18715705
TI  - Editorial comment on: endoscopic combined intrarenal surgery in Galdakao-modified
      supine Valdivia position: a new standard for percutaneous nephrolithotomy?

PMID- 18715706
TI  - Editorial comment on: endoscopic combined intrarenal surgery in Galdakao-modified
      supine Valdivia position: a new standard for percutaneous nephrolithotomy?

PMID- 18715707
TI  - Editorial comment on: endoscopic combined intrarenal surgery in Galdakao-modified
      supine Valdivia position: a new standard for percutaneous nephrolithotomy?

PMID- 18715708
TI  - Hydrodechlorination of DDT and chloroalkanes over carbon-supported Ni-Mo
      catalyst.
AB  - Catalytic hydrodechlorination (HDC) is an efficient method for the elimination of
      chlorinated compounds from organic wastes. HDC allows for the recovery of parent
      hydrocarbons. Herein, we studied the dechlorination of chlorododecane (CDD),
      dichlorocyclohexane (DCH) and dichlorodiphenyltrichloroethane (DDT) over a
      sulfided Ni-Mo/C catalyst in a flow reactor. The Ni-Mo/C catalyst was prepared by
      the incipient wetness method using a granular activated carbon support. In
      contrast to alumina, which is a commonly used support for commercial catalysts,
      the carbon support is resistant to decomposition by HCl formed during the HDC
      reaction. The composition of the tested catalyst was 5 wt.% NiO and 15 wt.%
      MoO(3), and it was characterized by well developed both the micro- and
      mesoporosity (V(mic)=0.559 cm(3)g(-1), V(mes)=0.430 cm(3)g(-1)). The level of
      conversion of CDD, DCH, and DDT was directly related to reaction temperatures in
      the HDC process; the total chlorine removal was achieved at 200 degrees C. The
      tested catalyst was determined to have good thermal stability in the HDC process
      at 170 degrees C for 100 h. This corresponded to conversions of 85-72% for CDD
      and 81-79% for DCH. For CDD the hydrogen pressure affected the ratio of dodecane
      to dodecene in the reaction products.

PMID- 18715709
TI  - Diclofenac removal from water with ozone and activated carbon.
AB  - Diclofenac (DCF) has been treated in water with ozone in the presence of various
      activated carbons. Activated carbon-free ozonation or single ozonation leads to a
      complete degradation of DCF in less than 15 min while in the presence of
      activated carbons higher degradation rates of TOC and DCF are noticeably
      achieved. Among the activated carbons used, P110 Hydraffin was found the most
      suitable for the catalytic ozonation of DCF. The influence of pH was also
      investigated. In the case of the single ozonation the increasing pH slightly
      increases the TOC removal rate. This effect, however, was not so clear in the
      presence of activated carbons where the influence of the adsorption process must
      be considered. Ecotoxicity experiments were performed, pointing out that single
      ozonation reduces the toxicity of the contaminated water but catalytic ozonation
      improved those results. As far as kinetics is concerned, DCF is removed with
      ozone in a fast kinetic regime and activated carbon merely acts as a simple
      adsorbent. However, for TOC removal the ozonation kinetic regime becomes slow. In
      the absence of the adsorbent, the apparent rate constant of the mineralization
      process was determined at different pH values. On the other hand, determination
      of the rate constant of the catalytic reaction over the activated carbon was not
      possible due to the effect of mass transfer resistances that controlled the
      process rate at the conditions investigated.

PMID- 18715710
TI  - A novel decomposition technique of friable asbestos by CHClF2-decomposed acidic
      gas.
AB  - Asbestos was widely used in numerous materials and building products due to their
      desirable properties. It is, however, well known that asbestos inhalation causes
      health damage and its inexpensive decomposition technique is necessary to be
      developed for pollution prevention. We report here an innovative decomposition
      technique of friable asbestos by acidic gas (HF and HCl) generated from the
      decomposition of CHClF(2) by the reaction with superheated steam at 800 degrees
      C. Chrysotile-asbestos fibers were completely decomposed to sellaite and
      magnesium silicofluoride hexahydrate by the reaction with CHClF(2)-decomposed
      acidic gas at 150 degrees C for 30 min. At high temperatures beyond 400 degrees
      C, sellaite and hematite were detected in the decomposed product. In addition,
      crocidolite containing wastes and amosite containing wastes were decomposed at
      500 degrees C and 600 degrees C for 30 min, respectively, by CHClF(2)-decomposed
      acidic gas. The observation of the reaction products by phase-contrast microscopy
      (PCM) and scanning electron microscopy (SEM) confirmed that the resulting
      products did not contain any asbestos.

PMID- 18715711
TI  - Long term studies on the anaerobic biodegradability of MTBE and other gasoline
      ethers.
AB  - Anaerobic biodegradation of methyl tert-butyl ether (MTBE) using electron
      acceptors such as nitrate, Fe(III), sulfate and bicarbonate, may be more cost
      effective and feasible compared to aerobic treatment methods, for dealing with
      the MTBE problem. Currently, there are a few reports in the literature which have
      documented anaerobic biodegradation of MTBE in batch studies. However, some of
      the reports have been controversial, additionally many other studies have failed
      to document anaerobic biodegradation. Experiments were conducted over a long term
      period in both batch and continuous reactors to investigate the anaerobic
      biodegradability of MTBE and other gasoline ethers. Inoculums collected from
      various environments were used, along with different electron acceptors. Only one
      set of the batch experiments showed a 30-60% conversion of MTBE to tert-butyl
      alcohol under Fe(III)-reducing conditions, using complexed Fe(III). The use of
      complexed Fe(III) created an initial low pH of 1-2 in these batches due to its
      acidic nature, therefore, the removal may be due to acid hydrolysis rather than
      biological processes. Based on the findings obtained, caution should be applied
      in the interpretation of experimental data in which complexed Fe(III) is used for
      bioremediation of MTBE.

PMID- 18715712
TI  - Degradation of formaldehyde in anaerobic sequencing batch biofilm reactor
      (ASBBR).
AB  - The present study evaluated the degradation of formaldehyde in a bench-scale
      anaerobic sequencing batch reactor, which contained biomass immobilized in
      polyurethane foam matrices. The reactor was operated for 212 days at 35 degrees C
      with 8h sequential cycles, under different affluent formaldehyde concentrations
      ranging from 31.6 to 1104.4 mg/L (formaldehyde loading rates from 0.08 to 2.78
      kg/m(3)day). The results indicate excellent reactor stability and over 99%
      efficiency in formaldehyde removal, with average effluent formaldehyde
      concentration of 3.6+/-1.7 mg/L. Formaldehyde degradation rates increased from
      204.9 to 698.3mg/Lh as the initial concentration of formaldehyde was increased
      from around 100 to around 1100 mg/L. However, accumulation of organic matter was
      observed in the effluent (chemical oxygen demand (COD) values above 500 mg/L) due
      to the presence of non-degraded organic acids, especially acetic and propionic
      acids. This observation poses an important question regarding the anaerobic route
      of formaldehyde degradation, which might differ substantially from that reported
      in the literature. The anaerobic degradation pathway can be associated with the
      formation of long-chain oligomers from formaldehyde. Such long- or short-chain
      polymers are probably the precursors of organic acid formation by means of
      acidogenic anaerobic microorganisms.

PMID- 18715713
TI  - Adsorption of arsenic(V) into modified lamellar Kenyaite.
AB  - The synthetic Kenyaite sample was used for organofunctionalization process with N
      propyldiethylenetrimethoxysilane and bis[3-(triethoxysilyl)propyl]tetrasulfide.
      The resulted materials were submitted to process of adsorption with arsenic
      solution at pH 2.0 and 298+/-1K. The adsorption isotherms were adjusted using a
      modified Langmuir equation with regression non-linear; the net thermal effects
      obtained from calorimetric titration measurements were adjusted to a modified
      Langmuir equation. The adsorption process was exothermic (Delta(int)H=-4.08 to 
      5.94 kJ mol(-1)) accompanied by increase in entropy (Delta(int)S=41.29-62.09 J K(
      1)mol(-1)) and Gibbs energy (Delta(int)G=-22.33 to -24.45 kJ mol(-1)). The
      energetic effect caused by metal cation adsorption was determined through
      calorimetric titration at the solid-liquid interface and gave a net thermal
      effect that enabled the calculation of the exothermic values and the equilibrium
      constant.

PMID- 18715714
TI  - Solar photocatalytic degradation of resorcinol a model endocrine disrupter in
      water using zinc oxide.
AB  - Photocatalytic degradation (PCD) of resorcinol a potent endocrine disrupting
      chemical in aqueous medium was investigated by ZnO under sunlight irradiation in
      a batch photoreactor. The influence of various parameters such as photocatalyst
      amount, initial concentration of resorcinol and pH was examined for maximum PCD
      of resorcinol. A considerable influence of pH upon the chemical oxygen demand
      (COD) disappearance was observed. In general, neutral or basic pH is favorable
      for COD removal of resorcinol. PCD intermediates were identified using FTIR and
      GC/MS. Two of the initial oxidation intermediates detected were 1,2,4-trihydroxy
      benzene and 1,2,3-trihydroxy-benzene. FTIR studies revealed 1,2,4-trihydroxy
      benzene as the major PCD intermediate. A working photodegradation mechanism is
      also suggested for PCD of resorcinol. This work envisages the great potential
      that sunlight mediated photocatalysis has in the removal of resorcinol from waste
      water.

PMID- 18715716
TI  - Measurement method of aberration from Ronchigram by autocorrelation function.
AB  - Aberrations up to the fifth-order were successfully measured using an
      autocorrelation function of the segmental areas of a Ronchigram. The method
      applied to aberration measurement in a newly developed 300kV microscope that is
      equipped with a spherical aberration corrector for probe-forming systems. The
      experimental Ronchigram agreed well with the simulated Ronchigram that was
      calculated by using the measured aberrations. The Ronchigram had an infinite
      magnification area with a half-angle of 50mrad, corresponding to the convergence
      angle of a uniform phase.

PMID- 18715717
TI  - Observation of three-dimensional elemental distributions of a Si device using a
      360 degrees -tilt FIB and the cold field-emission STEM system.
AB  - A technique for preparation of a pillar-shaped specimen and its multidirectional
      observation using a combination of a scanning transmission electron microscope
      (STEM) and a focused ion beam (FIB) instrument has been developed. The system
      employs an FIB/STEM compatible holder with a specially designed tilt mechanism,
      which allows the specimen to be tilted through 360 degrees [T. Yaguchi, M. Konno,
      T. Kamino, T. Hashimoto, T. Ohnishi, K. Umemura, K. Asayama, Microsc. Microanal.
      9 (Suppl. 2) (2003) 118; T. Yaguchi, M. Konno, T. Kamino, T. Hashimoto, T.
      Ohnishi, M. Watanabe, Microsc. Microanal. 10 (Suppl. 2) (2004) 1030]. This
      technique was applied to obtain the three-dimensional (3D) elemental
      distributions around a contact plug of a Si device used in a 90-nm technology. A
      specimen containing only one contact plug was prepared in the shape of a pillar
      with a diameter of 200nm and a length of 5mum. Elemental maps were obtained from
      the pillar specimen using a 200-kV cold-field emission gun (FEG) STEM model HD
      2300C equipped with the EDAX genesis X-ray energy-dispersive spectrometry (XEDS)
      system through a spectrum imaging technique. In this study, elemental
      distributions of minor elements with weak signals were enhanced by applying
      principal component analysis (PCA), which is a superior technique to extract weak
      signals from a large dataset. The distributions of elements, especially the
      metallization component Ti and minor dopant As in this particular device, were
      successfully extracted by PCA. Finally, the 3D elemental distributions around the
      contact plug could be visualized by reconstruction from the tilt series of maps.

PMID- 18715715
TI  - Functional up-regulation of P2X 3 receptors in the chronically compressed dorsal
      root ganglion.
AB  - P2X receptors on dorsal root ganglion (DRG) neurons have been strongly implicated
      in pathological nociception after peripheral nerve injuries or inflammation.
      However, nothing is known of a role for purinergic receptors in neuropathic pain
      produced by a chronic compression of DRG (CCD) - an injury that may accompany an
      intraforaminal stenosis, a laterally herniated disc or other disorders of the
      spine leading to radicular pain. In a rat model of DRG compression,
      hyperexcitable neurons retain functioning axonal connections with their
      peripheral targets. It is unknown whether such hyperexcitability might enhance
      chemically mediated nociceptive stimulation of the skin. In this study, CCD
      facilitated the nocifensive behavior and mechanical hyperalgesia-induced by the
      P2X 3 agonist, alpha,beta-methylene ATP (alpha,beta-meATP). An injection of
      alpha,beta-meATP into the hind paw of CCD rats resulted in a significantly
      greater decrease in the mean threshold to von Frey stimuli and a greater duration
      of paw lifts than in sham-operated control rats. CCD also increased the levels of
      P2X 3 receptor protein and the number of P2X 3 immunoreactive, small diameter DRG
      neurons in the compressed ganglion. P2X 3 receptors were co-labeled with the
      isolectin IB4, consistent with a role in nociception. In addition, a alpha,beta
      meATP induced significantly larger fast-inactivating currents in CCD- than in
      sham-operated acutely dissociated DRG neurons. These currents were accompanied by
      the generation of action potentials - but only in the CCD neurons. U0126, a
      specific inhibitor of the MEK1/2, greatly down-regulated the enhanced current.
      Taken together, these observations suggest that enhanced purinergic responses
      after CCD are mediated by P2X 3 receptors.

PMID- 18715718
TI  - Guar meal ameliorates Eimeria tenella infection in broiler chicks.
AB  - Guar meal contains relatively high levels of saponins, which are known to have
      antiprotozoal activity and may be effective against coccidiosis. A 2x2 factorial
      experiment investigated the impact of guar meal (0 or 5%) corn-soy-based starter
      broiler diets on chicks unchallenged or challenged with Eimeria tenella. At 1 day
      of age, 120 unsexed RossxRoss broiler chicks were randomly distributed among four
      treatment groups. Chicks were challenged with 5x10(3) sporulated oocysts of E.
      tenella in 0.5 ml at 10 days of age by oral gavage. Weekly body weight, body
      weight gains, feed conversion ratio and mortality rate were recorded for chicks
      fed from 0 to 21 days of age. Oocysts shed per gram feces were recorded from 6 to
      10 days post-challenge. Results showed that challenged chicks fed 0% guar meal
      had significantly higher oocysts per gram shed in feces than the other groups. No
      significant differences among treatment groups in mortality rate were observed.
      Body weights of unchallenged and challenged chicks fed 0% guar meal were
      significantly higher than those fed 5% guar meal at 2 weeks of age. Results
      indicated that including 5% guar meal in the diet of chicks challenged with E.
      tenella decreased oocysts shed per gram feces and prevented bloody diarrhea, but
      without affects on body weight and feed conversion ratio at 11 days post
      challenge.

PMID- 18715720
TI  - Marijuana and tobacco exposure predict affect-regulation expectancies in dual
      users.
AB  - In order to better compare affect-related expectancies for tobacco and marijuana
      smoking, associations of marijuana and tobacco exposure to negative affect
      reduction (NAR), positive affect enhancement (PAE), and related smoking outcome
      expectancies were assessed in young individuals who reported smoking both
      marijuana and tobacco on a regular basis (dual users). More frequent smoking of a
      given substance was associated with expectations of greater NAR and PAE by that
      substance while duration of exposure did not reliably predict NAR or PAE drug
      expectancies. Contrary to expectations, individuals anticipating greater NAR
      and/or PAE for one substance did not exhibit corresponding expectancies for the
      other drug. These findings suggest that exposure duration may be less important
      than current usage levels in influencing affect expectancies and that the affect
      related expectancies for tobacco and marijuana are largely independent of each
      other.

PMID- 18715721
TI  - Did the 1918 flu virus cause the Black Death?

PMID- 18715722
TI  - Survival of Naegleria fowleri primary amebic meningocephalitis (PAM) could be
      improved with an intensive multi-route chemo- and biotherapeutic regimen.
AB  - BACKGROUND: Naegleria fowleri primary amebic meningoencephalitis (PAM) has a very
      high mortality rate, probably exceeding 95%. A few people have survived after
      getting intravenous and intrathecal amphotericin, variably coupled with other
      agents that include dexamethasone, diflucan, chloramphenicol and rifampin, but
      even with prompt initiation of therapy, it is still a very uphill battle.
      PRESENTATION OF THE HYPOTHESIS: Survival could be improved by combined
      intrathecal, intranasal and intravenous amphotericin, diflucan and rifampin, with
      aduvant intravenous chloramphenicol, muramyl dipeptide, azithromycin, minocycline
      and linezolid, intramuscular trifluoperazine, intranasal Cry1C protoxin and
      intrathecal anti-Naegleria immune globulin and dexamethasone. HYPOTHESIS
      RATIONALE: Instilling medications intranasally, intravenously and intrathecally
      would target the primary reservoir of infection and its common sites of spread.
      Intrathecal dexamethasone should attenuate cerebral edema, a primary cause of
      death in PAM. Azithromycin and minocycline appear to have synergy with
      amphotericin in killing N. fowleri in animal models, and the other agents, which
      also showed efficacy in animal models, should also be additive or synergistic as
      well. In essence one would approach PAM in the manner of chemotherapy for
      tuberculosis and cancer, with multidrug therapy to assure complete eradication.
      TESTING THE HYPOTHESIS: The hypothesis could be validated using murine and bovine
      models of N. fowleri PAM. IMPLICATIONS OF THE HYPOTHESIS: PAM may be emerging as
      a significant public health threat, underscoring the need for effective
      therapeutic regimens.

PMID- 18715723
TI  - It is time for gene navigation surgeries.

PMID- 18715724
TI  - The etiology of optic neuritis in Asian population.

PMID- 18715725
TI  - A definition of drowsiness: one purpose for sleep?
AB  - While significant research has been done into the physiological mechanisms that
      underlie sleep and the sleep/wake cycle, the available data regarding the nature
      of drowsiness is far more limited. An objective measurement of drowsiness would
      have clinical utility, and a precise definition of the drowsy state could offer
      insights into the nature and purpose of sleep. Studies utilizing fMRI have
      demonstrated increased area of central nervous system involvement with tasks of
      increasing complexity. Preliminary data from studies of magnetoencephalography
      (MEG) with a receptive language task have demonstrated a progressive increase in
      global coherence of activity between MEG sensors with increasing drowsiness. The
      relationship between global coherence and the level of drowsiness suggests that
      the former may serve as an objective measurement of the latter. If true, the
      relationship suggests the hypothesis that drowsiness may be defined as a
      progressive loss of cortical network processing efficiency, requiring the
      recruitment of greater amounts of cortical tissue to perform the same task.

PMID- 18715726
TI  - Radiotherapy timing in 4,820 patients with breast cancer: university of florence
      experience.
AB  - PURPOSE: To analyze the relationship between a delay in radiotherapy (RT) after
      breast-conserving surgery and ipsilateral breast recurrence (BR). METHODS AND
      MATERIALS: We included in our analysis 4,820 breast cancer patients who had
      undergone postoperative RT at the University of Florence. The patients were
      categorized into four groups according to the interval between surgery and RT
      (T1, <60 days; T2, 61-120 days; T3, 121-180 days; and T4, >180 days). RESULTS: On
      multivariate analysis, the timing of RT did not reach statistical significance in
      patients who received only postoperative RT (n = 1,935) or RT and hormonal
      therapy (HT) (n = 1,684) or RT, chemotherapy (CHT), and HT (n = 529). In the
      postoperative RT-only group, age at presentation, surgical margin status, and a
      boost to the tumor bed were independent prognostic factors for BR. In the RT plus
      HT group, age at presentation and boost emerged as independent prognostic factors
      for BR (p = 0.006 and p = 0.049, respectively). Finally, in the RT, CHT, and HT
      group, only multifocality was an independent BR predictor (p = 0.01). Only in the
      group of patients treated with RT and CHT (n = 672) did multivariate analysis
      with stepwise selection show RT timing as an independent prognostic factor
      (hazard ratio, 1.59; 95% confidence interval, 1.01-2.52; p = 0.045). Analyzing
      this group of patients, we found that most patients included had worse prognostic
      factors and had received CHT consisting of cyclophosphamide, methotrexate, and 5
      fluorouracil before undergoing RT. CONCLUSION: The results of our study have
      shown that the timing of RT itself does not affect local recurrence, which is
      mainly related to prognostic factors. Thus, the "waiting list" should be thought
      of as a "programming list," with patients scheduled for RT according to their
      prognostic factors.

PMID- 18715727
TI  - Effect of different methods of cryopreservation on the cytoskeletal integrity of
      dromedary camel (Camelus dromedarius) embryos.
AB  - This study examined the effect of different methods of cryopreservation on the
      cytoskeletal integrity of camel embryos. A total of 32 embryos were recovered on
      Days 6 and 7 after ovulation and measured before being frozen using either a
      conventional slow-cooling technique (n=12: six Day 6 and six Day 7 embryos) or
      vitrification (n=12: four Day 6 and eight Day 7). The remaining 8 'control'
      embryos (four Day 6 and four Day 7) were not cryopreserved but instead incubated
      in holding medium for 30 min. After thawing, warming or incubation, the embryos
      were stained with 4,6-diamino-2-phenylindole dihydrochloride (DAPI) to identify
      dead cells. Subsequently, the embryos were fixed in 4% paraformaldehyde,
      permeabilized and labelled with Alexa Fluor 488-Phalloidin to enable assessment
      of cytoskeleton integrity. Vitrified-warmed embryos contained a significantly
      higher percentage of dead cells than either conventionally frozen embryos or
      controls (P<0.05). Although the proportion of dead cells in conventionally frozen
      embryos tended to be higher than in controls, the difference was not significant
      (P> or =0.07). Whereas embryo size did not affect the number of dead cells in
      conventionally frozen embryos, vitrified-warmed embryos >300 microm in diameter
      had a significantly higher percentage of dead cells than embryos < or =300 microm
      (P=0.01). Cytoskeleton integrity was also affected by both freezing method and
      embryo diameter. All 8 control embryos had a Grade I cytoskeleton, compared with
      only 2/24 (8.3%) frozen or vitrified embryos. Of the 8 slow-frozen or vitrified
      embryos with a Grade III cytoskeleton post-thaw, 7 had been vitrified and 6 were
      larger (Day 7) embryos. These results indicate that while both slow-freezing and
      vitrification of camel embryos lead to cytoskeleton disruption and cell death,
      embryo quality is better preserved by slow-freezing.

PMID- 18715728
TI  - An initial study of insect succession and carrion decomposition in various forest
      habitats of Central Europe.
AB  - At the end of summer and beginning of fall 2005 insect succession and pig carrion
      decomposition were studied in pine-oak forest, hornbeam-oak forest, and alder
      forest in Western Poland (Central Europe). Five stages of decomposition were
      recognized: fresh stage, bloated stage, active decay stage, advanced decay stage,
      and remains stage. The highest rate of decomposition was observed in the alder
      forest and the lowest in the pine-oak forest. A similar composition of carrion
      entomofauna was found in each forest. Numerous adults of Lucilia caesar, Phormia
      regina and Calliphora vomitoria (Calliphoridae), Hydrotaea spp. (Muscidae),
      Stearibia nigriceps and Parapiophila vulgaris (Piophilidae), Necrodes littoralis
      and Thanatophilus rugosus (Silphidae), Creophilus maxillosus, Omalium rivulare,
      Oxypoda acuminata and Philonthus spp. (Staphylinidae) as well as larvae of L.
      caesar, P. regina, C. vomitoria, Fannidae (Diptera) and N. littoralis, C.
      maxillosus, Philonthus (Coleoptera) were collected. There were no differences
      between forests in the sequence of insect occurrence on carrion. However,
      differences between forests in occurrence time and activity period of some taxa
      were found. Implications of these results for forensic entomology are discussed.

PMID- 18715729
TI  - The signal transduction mediated by erythropoietin and proinflammatory cytokines
      in the JAK/STAT pathway in the children with cerebral palsy.
AB  - It is well established that erythropoietin (EPO) is a pleiotropic cytokine, which
      has a brain-derived neuroprotective effect in the central nervous system (CNS).
      Immune abnormality has a close relationship with cerebral palsy (CP), and may be
      even involved in the development of CP. There is evidence that the amount of EPO
      in CP children is lower than in normal children, but the levels of
      proinflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor
      (TNF)-alpha, are higher in the CP children. The signal transduction mediated by
      EPO that has a neuroprotective effect and mediated by proinflammatory cytokines
      that lead to brain damage shares the common JAK/STAT pathway. Under acute stress,
      the JAK/STAT pathway is occupied by massive proinflammatory cytokines, and the
      negative feedback inhibition factors like suppressor of cytokine signaling (SOCS)
      proteins are simultaneously activated, which exist in reciprocal inhibition to
      EPO in the JAK/STAT pathway. As a result, the signal transduction mediated by EPO
      is prevented or reduced, and the neuroprotective effect of EPO is eventually
      weakened. In this review, a novel approach to CP treatment through
      neurodevelopmental treatment (NDT) is put forward by analysis of the
      interrelationship of signal transduction mediated by EPO and proinflammatory
      cytokines in the JAK/STAT pathway and their roles in the development of CP, and
      some reasonable ideas for CP treatment are provided.

PMID- 18715730
TI  - [Yellow fever vaccination in non-immunocompetent patients].
AB  - Any person travelling in countries where yellow fever (YF) is endemic and without
      presenting contra-indication for the vaccination against YF may be vaccinated.
      This vaccination can very rarely induce a potentially lethal neurotropic or
      viscerotropic disease. In severely immunodeficient patients, the vaccination is
      contra-indicated because postvaccinal encephalitis may occur after the
      vaccination, due to vaccine strain pathogenecity. It is important to evaluate the
      general health status in elderly individuals before vaccinating because of the
      increased risk of viscerotropic disease in people of 60 years of age and over.
      Pregnant women should not be vaccinated, except if departure to an endemic zone
      is unavoidable. YF vaccinatio is contra-indicated for newborns under six months
      of age. Solid organ grafts, congenital immunodeficiency, leukemia, lymphoma,
      cancer, and immunosuppressive treatments are contra-indications for this
      vaccination. Nevertheless, YF immunization is possible after a bone marrow graft
      and a two-year period without graft-versus-host disease or immunosuppressive
      treatment. There is no data to support that immunization of the dono prior to the
      graft could confer protection against yellow fever to the recipient. Low doses,
      short courses of corticosteroids either as systemic treatment or intra-articular
      injections are not contra-indications for YF vaccination. Patients infected with
      HIV with stable clinical status and T CD4-cel count above 200 cells per
      millimetre cube may be vaccinated. Thymic diseases, including thymoma and
      thymectomy, are contra-indications for YF vaccination. Finally, a substantial
      residual level of antibodies beyond 10 years after the latest vaccination could
      confer protection, thus avoiding a new vaccination when it is an issue.

PMID- 18715731
TI  - [Systematic family screening in case of infant pertussis].
AB  - The origin of contamination in pertussis of young infants is generally the close
      relatives. From 2000 to 2004, only serology and culture were available in our
      hospital. The families of 16 young infants (age below one year) hospitalized for
      pertussis were screened using serological tests: 21/48 contacts were positive.
      After 2004, PCR was available for exploration of index cases and families: 35/85
      contacts were positive. Of the mothers tested 23/46 were positive compared to
      14/41 fathers. Only one parent presented with a typical paroxystic pertussis
      cough, 60% presented with a nonparoxystic cough having lasted for more than five
      days and 40% of positive adults did not present with cough. Despite official
      recommendations, none of these young parents had received an antipertussis
      booster vaccination. This study shows the high frequency of atypical or
      nonsymptomatic pertussis in adults in the close family of infected young infants.
      These adults contribute to spreading the disease.

PMID- 18715732
TI  - An integrated system for dissolution studies and magnetic resonance imaging of
      controlled release, polymer-based dosage forms-a tool for quantitative assessment
      of hydrogel formation processes.
AB  - Controlled release (CR) dosage forms are often based on polymeric matrices, e.g.,
      sustained-release tablets and capsules. It is crucial to visualise and quantify
      processes of the hydrogel formation during the standard dissolution study. A
      method for imaging of CR, polymer-based dosage forms during dissolution study in
      vitro is presented. Imaging was performed in a non-invasive way by means of the
      magnetic resonance imaging (MRI). This study was designed to simulate in vivo
      conditions regarding temperature, volume, state and composition of dissolution
      media. Two formulations of hydrodynamically balanced systems (HBS) were chosen as
      model CR dosage forms. HBS release active substance in stomach while floating on
      the surface of the gastric content. Time evolutions of the diffusion region,
      hydrogel formation region and "dry core" region were obtained during a
      dissolution study of L-dopa as a model drug in two simulated gastric fluids (i.e.
      in fed and fasted state). This method seems to be a very promising tool for
      examining properties of new formulations of CR, polymer-based dosage forms or for
      comparison of generic and originator dosage forms before carrying out
      bioequivalence studies.

PMID- 18715733
TI  - In vitro activity of cefditoren and other antimicrobial agents against 288
      Streptococcus pneumoniae and 220 Haemophilus influenzae clinical strains isolated
      in Zaragoza, Spain.
AB  - In vitro cefditoren antimicrobial activity was tested against 288 Streptococcus
      pneumoniae and 220 Haemophilus influenzae clinical strains isolated in our
      hospital from January 2005 to May 2006 by agar dilution and broth microdilution
      method, respectively. MICs were also determined for 13 and 10 comparison drugs,
      respectively. The pneumococci tested comprised 113 (39.2%) penicillin
      susceptible, 91 (31.6%) penicillin intermediate, and 84 (29.2%) penicillin
      resistant. Cefditoren was the most active drug on the basis of the MICs
      (MIC(90)=0.5 microg/mL), followed by ceftriaxone and levofloxacin (MIC(90)=1
      microg/mL). Cefditoren MICs ranged from 0.25 to 1 microg/mL for ceftriaxone
      resistant isolates, with a modal MIC of 0.5 microg/mL and an MIC(90) of 1.0
      microg/mL. No S. pneumoniae isolates evaluated in this study showed MICs to
      cefditoren higher than 1 microg/mL (MIC range, <or=0.015 to 1 microg/mL). Against
      penicillin-resistant pneumococci, the rank order of intrinsic activity (MIC(90),
      microg/mL) was cefditoren (0.5)<ceftriaxone (2.0)=cefotaxime
      (2.0)<amoxicillin/clavulanate (8.0)=amoxicillin (8.0)=cefuroxime (8.0). Among the
      220 strains of H. influenzae, 42 (19.09%) produced a beta-lactamase (Hi beta+)
      and 3 (1.1%) were beta-lactamase (Hi beta-) negative but have reduced
      susceptibility to ampicillin (BLNAR). The most active drugs on the basis of MICs
      were cefditoren and levofloxacin, showing MIC(50) and MIC(90) values of
      0.015/0.06 microg/mL. Cefditoren at concentration of 0.06 microg/mL inhibited all
      3 BLNAR (ampicillin MICs >4 microg/mL). Against H. influenzae (Hi beta+), the
      rank order of intrinsic activity (MIC(90), microg/mL) was cefditoren (0.03) <
      cefixime (0.06)<ceftriaxone (0.12)=cefotaxime (0.12)<cefuroxime
      (1.0)<amoxicillin/clavulanate (2.0)<ampicillin (>8.0).

PMID- 18715734
TI  - Verticillium infection--a rare cause of hepatosplenic abscesses.
AB  - We report a rare case of hepatosplenic abscesses caused by Verticillium spp. in a
      40-year-old female leukemic patient. Identification of the microorganism was
      based on amplification of the D1-D2 region of the large-subunit RNA gene from DNA
      extracted from paraffin sections of liver tissue, followed by sequencing of the
      amplified polymerase chain reaction product.

PMID- 18715736
TI  - New rapid test for paratyphoid a fever: usefulness, cross-detection, and
      solution.
AB  - We described a 5-min colorimetric test for paratyphoid A fever, which detects
      anti-Salmonella O2 antibodies by inhibiting the binding between 2 types of
      reagent particles. This test (TUBEX-PA) is based on that (TUBEX-TF) used for
      typhoid fever, which detects anti-O9 antibodies. TUBEX-PA showed a sensitivity of
      81.0% (47/58 culture-confirmed patients) to 93.3% (14/15) and was 98.1% (52/53)
      specific for healthy subjects. However, TUBEX-PA also detected 50% (7/14) to
      81.8% (9/11) of typhoid patients, and conversely, TUBEX-TF detected 46.7% (7/15)
      to 73.3% (11/15) of paratyphoid A cases. This cross-detection could be abrogated
      in both tests by adding a blocker (heterologous antigen) to remove the antibodies
      responsible, which presumably bind to a common antigen (O12) located close to O2
      and O9. The presence of anti-O12 antibodies in typhoid (9/12 or 75.0% sensitive)
      and paratyphoid A (22/33 or 66.7%) patients was demonstrated directly using a
      prototypic TUBEX test designed specifically to detect these antibodies. Thus,
      using TUBEX-PA and TUBEX-TF together can increase the diagnostic accuracy of
      detecting both typhoid and paratyphoid A fever, while the further use of
      differential tests allows possible immediate discrimination between these
      diseases.

PMID- 18715735
TI  - Performance characteristics of the new ARCHITECT Toxo IgG and Toxo IgG Avidity
      assays.
AB  - The ARCHITECT Toxo IgG and IgG Avidity assays have been developed as a fully
      automated panel for immune status determination and acute infection exclusion.
      Resolved relative specificity and sensitivity of the ARCHITECT Toxo IgG assay
      were 99.6% (1359/1365) and 99.7% (1096/1099) as determined on pregnant females,
      blood donor, and diagnostic specimens. Seroconversion sensitivity of the
      ARCHITECT assay was comparable with the AxSYM Toxo IgG assay. The ARCHITECT Toxo
      IgG Avidity assay detected 100.0% (124/124) of acute phase specimens (<4 months
      after infection) as low avidity, whereas the Vidas Toxo IgG Avidity assay
      detected 98.9% (89/90) as low avidity. In summary, the ARCHITECT Toxo IgG assay,
      using recombinant antigens, showed excellent specificity and sensitivity for
      acute phase as well as past infection specimens. The ARCHITECT Toxoplasmosis
      panel can be reliably used to rule out acute Toxoplasma gondii infection in
      pregnant women.

PMID- 18715738
TI  - Community-associated methicillin-resistant Staphylococcus aureus, eastern
      Argentina.
AB  - Sixty-nine community-associated methicillin-resistant Staphylococcus aureus
      recovered in 6 healthcare centers from northeastern and eastern Argentina were
      genotyped by pulsed-field gel electrophoresis. The predominant pulsotype was
      widely distributed harbored SCCmec type IV and Panton-Valentine leukocidin genes.
      Representative isolates were characterized by multilocus sequence typing and spa
      typing, demonstrating that this clone belonged to ST5 and spa type 311.

PMID- 18715737
TI  - A duplex real-time reverse transcriptase polymerase chain reaction assay for the
      detection of St. Louis encephalitis and eastern equine encephalitis viruses.
AB  - A duplex TaqMan real-time reverse transcriptase polymerase chain reaction (PCR)
      assay was developed for the detection of St. Louis encephalitis virus (SLEV) and
      eastern equine encephalitis virus (EEEV), for use in human and vector
      surveillance. The respective targets selected for the assay were the conserved
      NS5 and E1 genes of the 2 viruses. Because of the insufficient number of NS5
      sequences from SLEV strains in the GenBank database, we determined the sequence
      of an approximately 1-kb region for each of 25 strains of SLEV to select primers
      and probes in a conserved region. Our assay has a sensitivity of 5 gene copies
      (gc)/reaction for EEEV and 10 gc/reaction for SLEV, and its performance is linear
      for at least 6 log(10) gc. The assay is specific and detected all strains of SLEV
      (69) and EEEV (12) that were tested. An internal control ensures detection of
      efficient nucleic acid extraction and possible PCR inhibition.

PMID- 18715739
TI  - Evaluation of loop-mediated isothermal amplification for detection of Toxoplasma
      gondii in water samples and comparative findings by polymerase chain reaction and
      immunofluorescence test (IFT).
AB  - The development and evaluation of a 1-step single-tube accelerated loop-mediated
      isothermal amplification (LAMP) assay for the rapid detection of Toxoplasma in
      water samples is described. The method has been evaluated based on the
      amplification of B1 and TgOWP Toxoplasma genes, and it demonstrated a sensitivity
      detection limit of 0.1 tachyzoites' DNA for both genes. LAMP detection was
      evaluated and compared with nested polymerase chain reaction (PCR) in 26 water
      sample pellets spiked with known numbers of Toxoplasma oocysts. After DNA
      extraction, the detection sensitivity in spiked pellets was 100% by LAMP and
      53.8% by PCR. Subsequently, 52 natural water samples of different origin were
      directly investigated by 3 assays: LAMP, PCR, and immunofluorescence test (IFT).
      Twenty-five (48%) of 52 have been found positive for Toxoplasma DNA by LAMP,
      whereas nested PCR products were generated in 7 of 52 (13.5%) water samples. All
      52 water samples were negative for Toxoplasma by IFT. These data clearly indicate
      LAMP as a rapid, specific, and sensitive tool for the detection of Toxoplasma
      contamination in water samples.

PMID- 18715740
TI  - Predictors of refusal during a multi-step recruitment process for a randomized
      controlled trial of arthritis education.
AB  - OBJECTIVE: Randomized controlled trials in patient education often have
      difficulty enrolling vulnerable populations-specifically, older, poorer, and less
      educated individuals. We undertook a randomized controlled trial (RCT) of an
      educational intervention for arthritis management, which included strategies to
      remove literacy-related barriers to participation. This paper reports on the
      multi-stage recruitment process and assesses whether refusal to participate was
      related to education, age, gender, working status, or insurance status. METHODS:
      The recruitment protocol was designed to eliminate literacy-related barriers to
      participation. Patients were never asked to read or fill out forms. Interactions
      were oral, using everyday terms and short, clear sentences. Patients who declined
      during a screening call were considered Stage 1 Refusers. Patients who initially
      expressed interest but neither completed a baseline questionnaire nor provided
      consent were considered Stage 2 Refusers. Patients who consented were considered
      Enrollees. Age, gender, and insurance status were compared between Stage 1
      Refusers and Enrollees. A second analysis compared these variables, plus
      educational attainment and working status, between Stage 2 Refusers, and
      Enrollees. RESULTS: Of 408 eligible patients, there were 193 (47.3%) Stage 1
      Refusers, 81 (19.9%) Stage 2 Refusers and 134 (32.8%) Enrollees. A higher
      proportion of Stage 1 Refusers than Enrollees were > or = 65 years old (58% vs.
      37%, p = .0003). Multivariate analysis, adjusting for gender and insurance
      status, confirmed the effect of older age on refusal (OR = 2.3 (1.4, 3.6)). There
      were no significant differences between Stage 2 Refusers and Enrollees.
      CONCLUSION: We found no evidence of refusal to participate due to educational
      attainment, working status, insurance status, or gender. Older patients were more
      likely to refuse participation at the first stage of recruitment. PRACTICE
      IMPLICATIONS: Researchers should continue efforts to increase participation among
      older patients, particularly when studies are designed to be generalized to an
      elderly population as is the case with arthritis research. Strategies used in
      this recruitment protocol designed to remove literacy-related barriers to
      recruitment may be responsible for the observation that subjects with lower
      education did not have a higher rate of refusal. Such strategies deserve further
      study.

PMID- 18715741
TI  - Factors affecting willingness to provide buprenorphine treatment.
AB  - Buprenorphine is an effective long-term opioid agonist treatment. As the only
      pharmacological treatment for opioid dependence readily available in office-based
      settings, buprenorphine may facilitate a historic shift in addiction treatment
      from treatment facilities to general medical practices. Although many patients
      have benefited from the availability of buprenorphine in the United States,
      almost half of current prescribers are addiction specialists suggesting that
      buprenorphine treatment has not yet fully penetrated general practice settings.
      We examined factors affecting willingness to offer buprenorphine treatment among
      physicians with different levels of prescribing experience. Based on their
      prescribing practices, physicians were classified as experienced, novice, or as a
      nonprescriber and asked to assess the extent to which a list of factors impacted
      their prescription of buprenorphine. Several factors affected willingness to
      prescribe buprenorphine for all physicians: staff training; access to counseling
      and alternate treatment; visit time; buprenorphine availability; and pain
      medications concerns. Compared with other physicians, experienced prescribers
      were less concerned about induction logistics and access to expert consultation,
      clinical guidelines, and mental health services. They were more concerned with
      reimbursement. These data provide important insight into physician concerns about
      buprenorphine and have implications for practice, education, and policy change
      that may effectively support widespread adoption of buprenorphine.

PMID- 18715742
TI  - Exposure to Adolescent Community Reinforcement Approach treatment procedures as a
      mediator of the relationship between adolescent substance abuse treatment
      retention and outcome.
AB  - Data from 399 adolescents, who participated in one of four randomly controlled
      trials of the Adolescent Community Reinforcement Approach (A-CRA) intervention,
      were used to examine the extent to which exposure to A-CRA procedures mediated
      the relationship between treatment retention and outcomes. Although zero-order
      correlations indicated that retention in treatment was a significant predictor of
      alcohol and other drug (AOD) use (r = -0.18, p < .001), this relationship was
      reduced to nonsignificance (p = .39) when exposure to A-CRA procedures was
      included in the model. Overall, the final model evidenced a very good fit (root
      mean square error of approximation = .00; comparative fit index = 1.00) and
      explained 29% and 43% of the variance in adolescents' posttreatment AOD use and
      AOD-related problems, respectively. In addition, Chi-Squared Automatic
      Interaction Detection analysis was used to derive a target level of A-CRA
      exposure, which was found to be significantly related to being in recovery at
      follow-up. The current findings are useful, as little research to date has
      identified significant mediators of the relationship between retention and
      treatment outcomes or identified target thresholds of treatment exposure.

PMID- 18715743
TI  - The relevance and treatment of cue-induced cravings in tobacco dependence.
AB  - Craving to smoke is often conceptualized and measured as a tonic, slowly changing
      state induced by abstinence. In this article, we review the literature on the
      existence, causes, and treatment of cue-induced cravings: intense, episodic
      cravings typically provoked by situational cues associated with drug use. In
      laboratory research, smokers exposed to smoking-related cues demonstrate
      increased craving as well as distinct patterns of brain activation. Observational
      field studies indicate that such cue-induced cravings are substantially
      responsible for relapse to smoking but that smoking can often be averted by
      coping responses. The effects of pharmacological interventions are mixed. Steady
      state medications (bupropion, varenicline, nicotine patch) do not appear to
      protect smokers from cue-induced cravings. However, acutely administered nicotine
      medications (such as nicotine gum and lozenge), used after cue exposure as
      "rescue medications," can help a smoker's recovery from cue-induced cravings. Cue
      induced craving plays an important role in smoking and relapse and likely in
      other addictions as well. Treatments to mitigate the effect of cue-induced
      craving are both important and needed.

PMID- 18715744
TI  - Substance-related problems and treatment among men who have sex with men in
      comparison to other men in Chicago.
AB  - This study compares a sample of urban men who have sex with men (MSM) with a
      general population sample of men in the same city on self-reported problems with
      substance use indicative of dependence and history of substance use treatment.
      Both samples were randomly selected using multistage probability methods. All
      participants completed audio computer-assisted self-interviews, including
      questions on substance use, problems related to substance use experienced in the
      past 12 months, and substance treatment. Problem use of alcohol, marijuana, and
      cocaine did not differ between samples. Compared to men in the general population
      sample, MSM were significantly more likely to experience problems related to the
      use of sedatives, tranquilizers, or prescription pain relievers. Among MSM,
      history of substance treatment was associated with a positive HIV test, and
      treatment usually preceded HIV diagnosis. Research is needed on effective methods
      for integrating HIV prevention for MSM into substance treatment settings,
      including physician-administered buprenorphine treatment for opiate addiction.

PMID- 18715745
TI  - Alcoholics Anonymous attendance following 12-step treatment participation as a
      link between alcohol-dependent fathers' treatment involvement and their
      children's externalizing problems.
AB  - We investigated longitudinal associations between alcohol-dependent fathers' 12
      step treatment involvement and their children's internalizing and externalizing
      problems (N = 125, M(age) = 9.8 +/- 3.1), testing the hypotheses that fathers'
      greater treatment involvement would benefit later child behavior and that this
      effect would be mediated by fathers' posttreatment behaviors. The initial
      association was established between fathers' treatment involvement and children's
      externalizing problems only, whereas Structural Equation Modeling (SEM) results
      supported mediating hypotheses. Fathers' greater treatment involvement predicted
      children's lower externalizing problems 12 months later, and fathers'
      posttreatment behaviors mediated this association: Greater treatment involvement
      predicted greater posttreatment Alcoholics Anonymous attendance, which in turn
      predicted greater abstinence. Finally, fathers' abstinence was associated with
      lower externalizing problems in children. Theoretical and practical implications
      of these findings are discussed.

PMID- 18715746
TI  - Smoking cessation during substance abuse treatment: what you need to know.
AB  - Patients in substance abuse treatment frequently smoke cigarettes and often die
      of tobacco-related causes. Substance abuse treatment programs too often ignore
      tobacco use. Many patients have expressed interest in stopping smoking, although
      they may be ambivalent about smoking cessation during substance abuse treatment.
      This article provides a review of tobacco cessation literature and successful
      methods of intervention. Research supports two key findings: (a) smoking
      cessation during substance abuse treatment does not impair outcome of the
      presenting substance abuse problem and (b) smoking cessation may actually enhance
      outcome success. We will discuss how to incorporate smoking cessation.

PMID- 18715747
TI  - Decreasing arm morbidity by refining axillary surgery in breast cancer.

PMID- 18715748
TI  - Long-term intrathecal ziconotide for chronic pain: an open-label study.
AB  - This open-label multicenter study evaluated the long-term safety and efficacy of
      intrathecal ziconotide and included 78 patients with chronic pain who had
      completed one of two previous ziconotide clinical trials. Each patient's initial
      ziconotide dose was based on his or her dose from the study of origin and was
      adjusted as necessary on the basis of adverse events and analgesic effect. The
      median ziconotide dose was 6.48 mcg/day (range, 0.00-120.00 mcg/day) at the
      Initial Visit and ranged from 5.52 to 7.20 mcg/day across all study visits. The
      most commonly reported new adverse events that were considered ziconotide related
      were memory impairment (11.3%); dizziness, nystagmus, and speech disorder (8.5%
      each); nervousness and somnolence (7.0% each); and abnormal gait (5.6%). There
      was no evidence of increased adverse event incidence at higher cumulative
      ziconotide doses. Elevations in creatine kinase were noted, but the proportion of
      patients with creatine kinase elevations did not change from the Initial Visit to
      the Termination Visit (4.1% each). Stable mean Visual Analog Scale of Pain
      Intensity scores during the three years of the study suggested no evidence of
      increased pain intensity with increased duration of ziconotide exposure. Long
      term treatment with ziconotide appeared to be well tolerated and effective in
      patients whose response to ziconotide and ability to tolerate the drug had been
      previously demonstrated.

PMID- 18715749
TI  - Challenges to and lessons learned from conducting palliative care research.
AB  - In response to a 2005 solicitation from the U.S. National Institutes of Health,
      16 investigators received funding to test interventions that would reduce the
      barriers that prevent cancer patients from receiving adequate and appropriate
      symptom management therapies. Since the awards have been issued, the
      investigators have met two times and have identified a number of challenges to
      implementing their respective studies. A survey was conducted that focused on
      their experiences with hiring and retaining study personnel, gaining
      Institutional Review Board approval, incurring unexpected costs, challenges to
      accruing participants, and a listing of standard measures used in the study. The
      survey was completed online by the Principal Investigator for each project in
      late 2006 and the initial results were confirmed one year later by resending the
      initial survey and by a follow-up telephone call. All but one Principal
      Investigator completed the survey. Obtaining Institutional Review Board approval,
      hiring and recruiting research personnel, establishing subcontracts, and accruing
      research subjects were the primary challenges experienced by the investigators.
      This palliative care solicitation achieved more than its original intent of
      stimulating research in overcoming barriers to delivering cancer symptom
      management, palliative care and end-of-life care. From a survey on the challenges
      and issues that emerged from their projects, grantees were able to identify
      specific hurdles and their unique solutions that may help other investigators as
      they plan their program of research.

PMID- 18715750
TI  - Multidimensional problems among advanced cancer patients in Cuba: awareness of
      diagnosis is associated with better patient status.
AB  - Cancer is one of the major causes of death in Cuba, and in current practice,
      patients are not usually informed of their diagnosis. Palliative care is an
      emerging discipline in this country. Cuban cancer patients with advanced disease
      completed the Palliative Outcome Scale (POS), and the researcher elicited
      patients' knowledge of their condition and prognosis. The POS consists of 12
      items that address the clinical, psychosocial, spiritual, family, and service
      delivery elements considered relevant to patients with advanced disease. Ten
      items are scored 0 (no problem) to 4 (worst problem), with one open-response
      question about the main problems experienced and one question about whether the
      questionnaire was completed with help or alone. Mann-Whitney tests were used to
      compare POS item scores by patient awareness. Of the 91 patients who participated
      in the study, 41% knew they had cancer and 9% were believed to be aware that they
      were dying. The most burdensome problems recorded on the POS were wasted time on
      appointments (70% of patients scored 3 or 4), pain (42%), patient anxiety (39%),
      and family anxiety (37%). Those patients who were aware of their diagnosis had
      statistically significantly better scores with respect to symptoms, patient
      anxiety, receiving information, and receiving support from family and friends.
      This study adds to knowledge about characteristics of terminal cancer patients in
      Cuba and the factors contributing to patient burden. It is the first study to
      explore the palliative care needs of Cuban patients with advanced cancer. An
      association has been demonstrated between patient knowledge and quality of life
      in Cuba, a setting where disclosure is contrary to current clinical practice.

PMID- 18715751
TI  - Detecting malingering in traumatic brain injury and chronic pain with an
      abbreviated version of the Meyers Index for the MMPI-2.
AB  - Meyers, Millis, and Volkert [Meyers, J. E., Millis, S. R., & Volkert, K. (2002).
      A validity index for the MMPI-2. Archives of Clinical Neuropsychology, 17, 157
      169] developed a method to detect malingering in chronic pain patients using
      seven scales from the Minnesota Multiphasic Inventory-2 (MMPI-2). This method may
      be impractical because two of the scales (Obvious minus Subtle and Dissimulation
      revised) are not reported by the commercially available Pearson computerized
      scoring system. The current study recalculated the Meyers Index using the five
      Pearson-provided scales in the chronic pain data sets of Meyers et al. [Meyers,
      J. E., Millis, S. R., & Volkert, K. (2002). A validity index for the MMPI-2.
      Archives of Clinical Neuropsychology, 17, 157-169] and Bianchini, Etherton,
      Greve, Heinly, and Meyers [Bianchini, K. J., Etherton, J. L., Greve, K. W.,
      Heinly, M. T., & Meyers, J. E. (in press). Classification accuracy of MMPI-2
      validity scales in the detection of pain-related malingering: A known-groups
      approach. Assessment], and the traumatic brain injury data of Greve, Bianchini,
      Love, Brennan, and Heinly [Greve, K. W., Bianchini, K. J., Love, J. M., Brennan,
      A., & Heinly, M. T. (2006). Sensitivity and specificity of MMPI-2 validity scales
      and indicators to malingered neurocognitive dysfunction in traumatic brain
      injury. The Clinical Neuropsychologist, 20, 491-512]. Classification accuracy of
      the abbreviated Meyers Index was comparable to the original. These findings
      demonstrate that the abbreviated Meyers Index can be used as a substitute of the
      original Meyers Index without decrements in classification accuracy.

PMID- 18715752
TI  - Inhibition of experimental autoimmune myocarditis: peripheral deletion of TcR
      Vbeta 8.1, 8.2+ CD4+ T cells in TLR-4 deficient mice.
AB  - Toll-like receptors (TLR) are pattern recognition receptors that are an essential
      feature of host defense against pathogens. Expression of TLR-4 on dendritic cells
      was reported to be required for initiation of experimental autoimmune myocarditis
      (EAM) but the mechanism by which TLR-4 signaling affects autoimmunity is
      incompletely understood. To determine the role of TLR-4 in EAM, wild type and TLR
      4-/- mice were immunized with myosin peptide (614-629) in CFA. TLR-4-/- mice
      demonstrated decreased myosin specific proliferation and decreased production of
      INF-gamma and IL-2. Immunization with myosin induced greater severity of
      myocarditis in wild type compared to TLR-4-/- mice as evidenced by lesions in the
      myocardium. TcR Vbeta 8.1, 8.2+ CD4+ T cells, detected in lesions were isolated
      from splenocytes by flow cytometry and found to undergo increased apoptosis in
      TLR-4-/- mice. In situ immunohistochemistry showed increased colocalization of
      cleaved caspase 3 and TcR Vbeta 8.1, 8.2+ CD4+ T cells in TLR-4-/- mice compared
      to wild type. Increased apoptosis was associated with impaired activation of NF
      kB p65 and decreased cell viability in the presence of TNF-alpha. These results
      demonstrate that infiltrating TcR Vbeta 8.1, 8.2+ CD4+ T cells are deleted by the
      mechanism of apoptosis in TLR-4-/- mice with EAM.

PMID- 18715753
TI  - A new method to induce multi-drug resistance to carboplatin in a mouse model of
      human tongue squamous cell carcinoma.
AB  - Multi-drug resistance (MDR) in human head and neck squamous cell carcinoma
      (HNSCC) constitutes a major obstacle to the effectiveness of chemotherapy. In
      previous studies, MDR was mainly induced in vitro. The authors report a novel in
      vivo method of inducing MDR in nude mice with xenotransplanted Tca8113 cells.
      Carboplatin, a chemotherapeutic agent used to treat HNSCC, was injected around
      the tumors for 10 weeks. A subsequent cell survival assay of dissociated tumor
      cells suggested that MDR had been induced successfully. Immunocytochemistry,
      reverse transcription polymerase chain reaction and Western blot analysis showed
      that the expression levels of MDR-related proteins, including topoisomerase II,
      MRP and glutathione transferase, were elevated in the induction group. The
      authors conclude that in vivo induction of MDR provides a useful method for
      establishing animal models of MDR.

PMID- 18715755
TI  - Neurocognitive enhancement therapy with vocational services: work outcomes at two
      year follow-up.
AB  - Neurocognitive enhancement therapy (NET) is a remediation program for the
      persistent and function-limiting cognitive impairments of schizophrenia. In a
      previous study in veterans, NET improved work therapy outcomes as well as
      executive function and working memory. The present study aimed to determine
      whether NET could enhance functional outcomes among schizophrenia and
      schizoaffective patients in a community mental health center receiving community
      based vocational services. METHOD: Patients (N=72) participated in a hybrid
      transitional and supported employment program (VOC) and were randomized to either
      NET+VOC or VOC only. NET+VOC included computer-based cognitive training, work
      feedback and a social information information-processing group. VOC only also
      included two weekly support groups. Active intervention was 12 months with 12
      month follow-up. Follow-up rate was 100%. RESULTS: NET+VOC patients worked
      significantly more hours during the 12 month follow-up period, reached a
      significantly higher cumulative rate of competitive employment by the sixth
      quarter, and maintained significantly higher rates of employment. CONCLUSION: NET
      training improved vocational outcomes, suggesting the value of combining
      cognitive remediation with other rehabilitation methods to enhance functional
      outcomes.

PMID- 18715754
TI  - Impact of protein kinase C activation on epileptiform activity in the hippocampal
      slice.
AB  - There is evidence suggesting that protein kinase C (PKC) activation can prevent
      the enhanced network excitability associated with status epilepticus and group I
      metabotropic glutamate receptor (mGluR)-induced epileptogenesis. However, we
      observed no suppression of mGluR-induced burst prolongation in the guinea pig
      hippocampal slice when applied in the presence of the PKC activator phorbol-12,13
      dibutyrate (PDBu). Furthermore, PDBu alone converted picrotoxin-induced
      interictal bursts into ictal-length discharges ranging from 2 to 6s in length.
      This effect could not be elicited by the inactive analog 4-alpha-PDBu and was
      suppressed with the PKC inhibitor chelerythrine, indicating PKC dependence. PKC
      activation can enhance neurotransmitter release, and both glutamate and
      acetylcholine are capable of eliciting similar prolonged synchronized discharges.
      However, neither mGluR1 nor NMDA receptor antagonist suppressed PDBu-driven burst
      prolongation, suggesting that increased glutamate release alone is unlikely to
      account for the PKC-induced expression of ictaform discharges. Similarly,
      atropine, a broad-spectrum muscarinic receptor antagonist, had no effect on PKC
      induced burst prolongation. By contrast, AMPA/kainate receptor antagonist
      abolished PKC-induced burst prolongation, and mGluR5 antagonist significantly
      blunted the maximum burst length induced by PKC. These data suggest that PKC
      induced prolongation of epileptiform bursts is dependent on changes specific to
      mGluR5 and AMPA/kainate receptors and not mediated simply by a generalized
      increase in transmitter release.

PMID- 18715756
TI  - Intrinsic motivation, neurocognition and psychosocial functioning in
      schizophrenia: testing mediator and moderator effects.
AB  - BACKGROUND: This study examined the nature of the relationships among
      neurocognition, intrinsic motivation, and psychosocial functioning for persons
      with schizophrenia. Hypotheses concerning both mediator and moderator mechanisms
      were tested. METHOD: 120 individuals diagnosed with schizophrenia were recruited
      as they entered outpatient psychosocial rehabilitation programs. Measures of
      psychosocial functioning and intrinsic motivation were administered at baseline.
      Measures of neurocognition were administered at baseline by testers blind to
      scores on other study variables. Data were analyzed using latent construct
      modeling to test for mediator and moderator effects. RESULTS: There were strong
      bivariate relationships between neurocognition, intrinsic motivation, and
      psychosocial functioning. The results demonstrated that intrinsic motivation
      strongly mediated the relationship between neurocognition and psychosocial
      functioning. This mediation was evidenced by: (i) the direct path from
      neurocognition to functional outcome no longer being statistically significant
      after the introduction of motivation into the model, (ii) the statistical
      significance of the indirect path from neurocognition through motivation to
      functional outcome. There was no support for the two moderation hypotheses: the
      level of neurocognition did not influence the relationship between intrinsic
      motivation and psychosocial functioning, nor did the level of intrinsic
      motivation influence the relationship between neurocognition and psychosocial
      functioning. CONCLUSIONS: Neurocognition influences psychosocial functioning
      through its relationship with intrinsic motivation. Intrinsic motivation is a
      critical mechanism for explaining the relationship between neurocognition and
      psychosocial functioning. Implications for the theoretical understanding and
      psychosocial treatment of intrinsic motivation in schizophrenia are discussed.

PMID- 18715757
TI  - Genetic associations with schizophrenia: meta-analyses of 12 candidate genes.
AB  - Genetic association studies on schizophrenia (SZ) have been repeatedly performed
      over the last two decades, resulting in a consensus that results are generally
      inconsistent. This consensus has begun to change as a result of meta-analyses
      (e.g., [Glatt, S.J. and Jonsson, E.G., 2006. The Cys allele of the DRD2 Ser311Cys
      polymorphism has a dominant effect on risk for schizophrenia: evidence from fixed
      and random-effects meta-analyses. Am. J. Med. Genet. B. Neuropsychiatr. Genet.
      141, 149-154.]). The SchizophreniaGene database
      (http://www.schizophreniaforum.org/res/sczgene/default.asp) has been a leader in
      meta-analyses of SZ association data, by dynamically and comprehensively
      cataloging all public genetic association studies, and preparing meta-analyses of
      case-control data. There are 19 "top" candidate genes from these analyses (access
      on December 20, 2007), showing the highest effect sizes and nominally significant
      associations of at least one variant in the meta-analyses of all ethnic samples
      or of samples of Caucasian ancestry. We selected 40 polymorphisms in 12 selected
      "top" genes for additional meta-analyses, which had at least one familial
      association data. We found gene-wide (correction for the number of meta-analyses
      for each gene) significant allelic association evidence for seven genes in the
      combined samples. The odds ratios (ORs) of the associated minor risk alleles
      range from 1.072 to 1.121, for DRD4, MTHFR, PPP3CC and TP53. For protective
      allele associations, the ORs are between 0.842 and 0.886, for DAO, IL1B, and
      SLC6A4. In population-based sub-analyses, we found significant results in four
      genes in Asians (ORs between 1.084 and 1.309 for DRD4, GABRB2, PPP3CC, and TP53),
      and one gene in European (OR of 0.888 for SLC6A4). The association of rs1816072
      of GABRB2 with SZ in Asians was significant (adjusted P=0.048 after correction
      for 80 tests). No significant heterogeneity between case-control and family-based
      study designs was detected in 35 out of 40 polymorphisms. Our results further
      support eight potential SZ candidate genes and suggest that family data can
      reasonably be included in the meta-analysis of genetic associations.

PMID- 18715758
TI  - Adjunctive therapies for severe sepsis.
AB  - Severe sepsis-associated mortality may still be improved by earlier recognition,
      faster and adequate source control, and targeted resuscitation. Patients who may
      benefit from the administration of drotrecogin alfa (activated) are currently
      those at high risk of death, and other indications should be better defined by
      ongoing trials. Use of low-dose steroids for the treatment of severe sepsis must
      be re-clarified by new studies and should be restricted to patients with
      refractory septic shock. Trials exploring the role of natural anticoagulants and
      Toll-like receptor inhibitors are ongoing and should be completed in the coming 3
      years. Future trials in severe sepsis should target more homogeneous populations
      with a well-defined focus of infection and severity, receiving appropriate
      standard of care, and the tested intervention should be administered in a timely
      fashion according to the expected host response.

PMID- 18715759
TI  - In vitro and in vivo potency of polymyxin B against IMP-type metallo-beta
      lactamase-producing Pseudomonas aeruginosa.
AB  - Multidrug-resistant Pseudomonas aeruginosa, especially metallo-beta-lactamase
      (MBL)-producing P. aeruginosa, is an important pathogen in nosocomial infection
      and emergence of this pathogen has revived interest in polymyxin B (PMB) and
      colistin (COL). In this study, we evaluated the efficacies of PMB, COL and other
      antipseudomonal agents against IMP-type MBL-producing P. aeruginosa both in vitro
      and in vivo. A total of 75 isolates of bla(IMP)-positive P. aeruginosa obtained
      from clinical specimens (94.6% of isolates demonstrated resistance to beta
      lactam, fluoroquinolone and aminoglycoside agents) were evaluated in the in vitro
      study. More than 90% of the examined isolates were susceptible to PMB (minimum
      inhibitory concentration for 50/90% of the isolates (MIC(50)/MIC(90)) 4/4 mg/L),
      although COL was less potent (MIC(50)/MIC(90) 8/16 mg/L). Cyclophosphamide
      treated mice were intraperitoneally inoculated with bla(IMP)-positive P.
      aeruginosa. Treatment with PMB, but not COL, imipenem/cilastatin or aztreonam,
      significantly improved the survival rate and decreased the number of bacteria in
      the blood in a dose-dependent manner. Our results indicate that, among the agents
      studied, PMB is the most effective agent against bla(IMP)-positive P. aeruginosa.

PMID- 18715760
TI  - Staphylococcus aureus bacteraemia with known sources.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA), both hospital-acquired and
      community-acquired MRSA (CA-MRSA) strains, have increased in frequency in the
      last few years, reaching epidemic dimensions. This review discusses several
      clinical forms of staphylococcal infection leading to bacteraemia in a high
      proportion of cases. Staphylococcal (MRSA) bacteraemic pneumonia is predominantly
      seen in hospital-acquired pneumonia and ventilator-associated pneumonia, reaching
      a frequency of 8.4% of all bacteraemias, 30% of all nosocomial bacteraemias and
      68% of all bacteraemias of patients hospitalised in Intensive Care Units. In
      patients with CA-MRSA pneumonia, the rate of bacteraemia is as high as 62%.
      Whereas in nosocomial bacteraemic pneumonia blood cultures become positive on the
      ninth day of pneumonia, in CA-MRSA bacteraemic pneumonia positive blood cultures
      appear early in the course of the infection. The pneumonia has a stormy course
      with the development of abscesses, empyema and extensive pulmonary damage.
      Vertebral osteomyelitis commonly occurs during intravenous catheter use, causing
      local thrombophlebitis that will seed to vertebral bodies and disks and may cause
      secondary sustained bacteraemia. Non-vertebral osteomyelitis is also on the
      increase, with a frequency that has doubled in recent years, mainly due to MRSA.
      Patients with haematological malignancies are particularly prone to this
      complication, usually following line infections. Epidural abscess is the most
      serious consequence of staphylococcal bacteraemia, leading to permanent
      neurological damage if not diagnosed early enough.

PMID- 18715761
TI  - Efficacy of ME1036 against meticillin-resistant Staphylococcus aureus and
      vancomycin-insensitive S. aureus in a model of haematogenous pulmonary infection.
AB  - ME1036, a novel parenteral carbapenem, was developed for the treatment of
      meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate S.
      aureus (VISA). A model of haematogenous pulmonary infection was induced in mice
      by tail vein injection of MRSA strain NUMR101 or VISA Mu50 enmeshed in agar
      beads. After 24h of infection, mice were treated twice daily for 7 days with
      200mg/kg/day vancomycin (VCM) or ME1036. Mice infected with VISA were also pre
      treated with cyclophosphamide to induce an immunocompromised state. The number of
      viable bacteria in the lungs was counted 12h after the final drug treatment. VCM
      decreased the number of viable MRSA in the lungs in comparison with the control,
      although the difference was not significant (mean+/-standard error of the mean
      log(10) colony-forming units (CFU)/lung=6.876+/-0.54 vs. 8.25+/-0.41,
      respectively). In contrast, treatment with ME1036 resulted in a significant
      decrease in the number of viable MRSA (log(10)CFU/lung=2.69+/-0.44 (n=6);
      P<0.0001) compared with both the VCM-treated and control mice. In the VISA
      infected mice, ME1036 significantly reduced the number of viable bacteria
      compared with VCM and control (log(10)CFU/lung=3.65+/-0.68 for ME1036 vs. 5.71+/
      0.75 for VCM (P<0.05) and 7.07+/-0.45 for control (P<0.001)). ME1036 produced >3
      log(10) reduction versus control against both MRSA strains (>5 log for the VCM
      susceptible strain and 3.4 log for the VISA), whereas VCM produced <1.3 log for
      both strains.

PMID- 18715762
TI  - Urinary bactericidal activity of single doses (250, 500, 750 and 1000 mg) of
      levofloxacin against fluoroquinolone-resistant strains of Escherichia coli.
AB  - Increasing resistance to fluoroquinolones in uropathogens has become a clinical
      concern. The purpose of this study was to analyse the urinary bactericidal
      activity (UBA) of levofloxacin against fluoroquinolone-resistant strains of
      Escherichia coli. Ten healthy adult subjects (aged 23-60 years) received single
      doses of levofloxacin (250, 500, 750 and 1000 mg) and then blood and urine
      samples were collected in intervals (0-1.5, 1.5-4, 4-8, 8-12 and 12-24h) over
      24h. Both serum and urine concentrations were measured by a validated high
      performance liquid chromatography assay. Bactericidal titres in urine were
      determined against E. coli isolates with minimum inhibitory concentrations of
      0.125, 4, 8, 16, 32 and 64microg/mL for levofloxacin. The mean serum
      pharmacokinetic parameters for these doses of levofloxacin were similar to
      previously published values. The mean peak urinary concentrations (0-1.5h) were
      210, 347, 620 and 536microg/mL for the 250, 500, 750 and 1000 mg dose,
      respectively. Each dose of levofloxacin exhibited early (0-1.5h time period)
      bactericidal activity in urine in virtually all subjects against E. coli strains
      with MICs<or=32microg/mL. Moreover, high-dose (750 mg and 1000 mg) levofloxacin
      provided prolonged (8-12h time period) bactericidal activity in 9/10 subjects
      against E. coli isolates with MICs up to 32microg/mL. In summary, this ex vivo
      investigation found that high-dose levofloxacin can produce early and prolonged
      UBA against fluoroquinolone-resistant strains of E. coli. Patient outcome studies
      are needed to determine whether these findings translate into clinical cures.

PMID- 18715763
TI  - First identification of VIM-1-producing Citrobacter freundii in Greece.

PMID- 18715764
TI  - Effect of subinhibitory concentrations of cumin (Cuminum cyminum L.) seed
      essential oil and alcoholic extract on the morphology, capsule expression and
      urease activity of Klebsiella pneumoniae.
AB  - Cuminum cyminum L., commonly known as cumin, is a plant with a considerable
      reputation. The aim of this work was to study the activity of cumin seed
      essential oil and alcoholic extract against Klebsiella pneumoniae ATCC 13883 and
      clinical K. pneumoniae isolates by evaluating the effect of subminimum inhibitory
      concentrations (sub-MICs) on cell morphology, capsule expression and urease
      activity. Growth of K. pneumoniae strains exposed to sub-MICs of C. cyminum
      extracts resulted in cell elongation and repression of capsule expression. Urease
      activity was decreased. The major constituent of the oil determined by gas
      chromatography/mass spectrometry was cumin aldehyde.

PMID- 18715766
TI  - 80th Anniversary of the discovery of penicillin An appreciation of Sir Alexander
      Fleming.

PMID- 18715765
TI  - Virulence and antimicrobial resistance in clinical Enterococcus faecium.
AB  - The aim of the present study was to determine the occurrence of seven virulence
      determinants in Enterococcus faecium clinical blood culture isolates over a 6
      year period and to investigate possible correlations between virulence and
      antibiotic resistance. Two hundred and sixty-three isolates were screened for the
      presence of genes coding for aggregation substance (asa1), cytolysin (cylA),
      collagen-binding protein (ace), Enterococcusfaecalis endocarditis antigen
      (efaA(fs)), enterococcal surface protein (esp(fm)), gelatinase (gelE) and
      hyaluronidase (hyl(fm)) by polymerase chain reaction. The minimum inhibitory
      concentrations (MICs) of ampicillin, ciprofloxacin, gentamicin, imipenem,
      linezolid and vancomycin were determined by the agar dilution method and the MIC
      of daptomycin was determined by Etest. The esp(fm) gene was found in 56% of the
      isolates, hyl(fm) in 4%, whilst the other virulence genes were detected only
      sporadically (< or = 1%). The level of antibiotic resistance was 77% to
      ampicillin, 90% to ciprofloxacin and 83% to imipenem; 5% of the isolates were
      resistant to vancomycin and 2% were resistant to gentamicin (high-level
      resistance, MIC > or = 500 mg/L). A significant correlation was found between the
      presence of esp(fm) and resistance to ampicillin, ciprofloxacin and imipenem
      (P<0.01). Twelve isolates were esp(fm)-positive and ampicillin-susceptible.

PMID- 18715767
TI  - Recovery of susceptibility to penicillin G in clinical isolates of Streptococcus
      pneumoniae despite increased accumulation of pbp gene alterations.
AB  - Two hundred consecutive clinical isolates of Streptococcus pneumoniae isolated in
      2005 and 2006 were analysed for susceptibility to various antimicrobials, pbp
      gene alterations and macrolide resistance gene expression (2007 analysis) and the
      results were compared with previous data (2003 analysis). The average minimum
      inhibitory concentration (MIC) of penicillin G in isolates with 1a(m)/2x(m)/2b(m)
      decreased from 1.135+/-0.503 mg/L in the 2003 analysis to 0.872+/-0.540 mg/L in
      the 2007 analysis (P=0.0046). The prevalence of isolates with 1a(m)/2x(m)/2b(m)
      increased from 30.5% to 32.3%, but the difference was not statistically
      significant (P=0.6979). The prevalence of isolates with a clarithromycin MIC > or
      = 1.0mg/L increased from 65.9% to 80.0% (P=0.0005). Isolates expressing ermB
      increased from 46.6% to 62.6% (P=0.0004). We conclude that the decrease in
      penicillin resistance of S. pneumoniae does not correlate with a decrease in pbp
      mutations; on the contrary, the prevalence of isolates with pbp mutations
      increased. A decrease in penicillin resistance in S. pneumoniae with pbp
      mutations appears to explain the present results regarding the recovery of
      penicillin susceptibility. Our results suggest that the spread of mutated pbp
      genes among S. pneumoniae itself is not responsible for acquisition of the
      penicillin-resistant phenotype. Use of beta-lactams, especially oral
      cephalosporins, appears to be responsible for the acquisition of penicillin
      resistance.

PMID- 18715768
TI  - Risk factors for mortality and clinical implications of catheter-related
      infections in patients with bacteraemia caused by Stenotrophomonas maltophilia.

PMID- 18715769
TI  - Amperometric determination of H2O2 at nano-TiO2/DNA/thionin nanocomposite
      modified electrode.
AB  - We report electrochemical preparation and characterization of a new biosensor
      made of nanostructured titanium dioxide (nano-TiO2) particles and
      deoxyribonucleic acid (DNA). Thionin (TN) redox mediator was electrochemically
      deposited onto DNA/nano-TiO2 modified glassy carbon electrode (GCE). The X-ray
      diffraction analysis, atomic force microscope (AFM) and scanning electron
      microscope (SEM) were used for surface analysis of TN/DNA/nano-TiO2 film. In
      neutral buffer solution, TN/DNA/nano-TiO2/GCE biosensor exhibited excellent
      electrocatalytic activity towards the reduction of hydrogen peroxide (H2O2) and
      oxygen (O2). The biosensor shows excellent analytical performance for
      amperometric determination of H2O2, at reduced overpotential (-0.2V). The
      detection limit and liner calibration range were found to be 0.05 mM (S/N=3) and
      0.05-22.3 mM, respectively. In addition, determination of H2O2 in real samples
      was carried out using the new biosensor with satisfactory results. The
      TN/DNA/nano-TiO2/GCE showed stable and reproducible analytical performance
      towards the reduction of H2O2. This biosensor can be used as an amperometric
      biosensor for the determination of H2O2 in real samples.

PMID- 18715770
TI  - A cognitive architecture for robot self-consciousness.
AB  - OBJECTIVE: One of the major topics towards robot consciousness is to give a robot
      the capabilities of self-consciousness. We propose that robot self-consciousness
      is based on higher order perception of the robot, in the sense that first-order
      robot perception is the immediate perception of the outer world, while higher
      order perception is the perception of the inner world of the robot. METHODS AND
      MATERIAL: We refer to a robot cognitive architecture that has been developed
      during almost 10 years at the RoboticsLab of the University of Palermo. The
      architecture is organized in three computational areas. The subconceptual area is
      concerned with the low level processing of perceptual data coming from the
      sensors. In the linguistic area, representation and processing are based on a
      logic formalism. In the conceptual area, the data coming from the subconceptual
      area are organized in conceptual categories. RESULTS: To model higher order
      perceptions in self-reflective agents, we introduce the notion of second-order
      points in conceptual space. Each point in this space corresponds to a self
      reflective agent, i.e., the robot itself, persons, and other robots with
      introspective capabilities. CONCLUSIONS: The described model of robot self
      consciousness, although effective, highlights open problems from the point of
      view of the computational requirements of the current state-of-art computer
      systems. Some future works that lets the robot to summarize its own past
      experiences should be investigated.

PMID- 18715771
TI  - Artificial consciousness: hazardous questions (and answers).
AB  - If human consciousness is the result of complex neural electro-chemical
      interactions occurring in the brain, the question of whether a machine can ever
      become self-aware could be a matter of time: the time necessary to fully
      understand the functional behavior of the brain structure, develop a mathematical
      model of it, and implement an artificial system capable of working according to
      such a model. This paper addresses several issues related to the possibility of
      developing a conscious artificial brain. A number of hazardous questions are
      posed to the reader, each addressing a specific technical or philosophical issue,
      which is discussed and developed in a form of a hazardous answer.

PMID- 18715772
TI  - Respiratory disorders are not more common in farmers. Results from a study on
      Icelandic animal farmers.
AB  - RATIONALE: The current prevalence of respiratory disorders and symptoms in
      Icelandic farmers is unknown, but a high prevalence of respiratory symptoms has
      been reported in the past. Modern farming practices have been implemented in
      Iceland in the past decade and the processing of hay has changed markedly leading
      to less organic dust exposure. OBJECTIVE: The aim was to estimate the prevalence
      of respiratory disorders and symptoms in a nationwide study of Icelandic farmers.
      METHODS: We conducted a questionnaire-based study of all Icelandic farmers with a
      comparison group randomly selected from the national citizen registry of Iceland.
      The questionnaire included items regarding respiratory symptoms and disorders.
      RESULTS: Out of 2042 farmers invited to participate, 1107 responded (54%), as did
      689 of 1500 controls (46%). Farmers were slightly older and more likely to be
      male (87% vs. 47%). Smoking rates were significantly lower among farmers than
      among controls. The prevalence of asthma was not significantly different between
      the two groups, with a lifetime prevalence of 9.4% (n=104) among farmers compared
      to 10.2% (n=70) among controls. Medication use for asthma was not significantly
      different. The prevalence of self-reported, physician-diagnosed chronic
      bronchitis and emphysema likewise did not significantly differ between the
      groups, but self-reported hay fever was significantly more prevalent among
      farmers. CONCLUSION: The prevalence of respiratory disorders and symptoms among
      Icelandic farmers is currently similar to non-farmers. This may suggest that
      modernization of the agricultural environment has had a positive effect on
      workers' health.

PMID- 18715773
TI  - Characterization of Caco-2 and HT29-MTX cocultures in an in vitro digestion/cell
      culture model used to predict iron bioavailability.
AB  - Cocultures of two human cell lines, Caco-2 and HT29-MTX mucus-producing cells,
      have been incorporated into an in vitro digestion/cell culture model used to
      predict iron bioavailability. A range of different foods were subjected to in
      vitro digestion, and iron bioavailability from digests was assessed with Caco-2,
      Caco-2 overlaid with porcine mucin, HT29-MTX or cocultures of Caco-2 and HT29-MTX
      at varying ratios. It was found that increasing the ratio of HT29-MTX cells
      decreased the amount of ferritin formed and resulted in an overall decline in the
      ability of the model to detect differences in iron bioavailability. At the
      physiologically relevant ratios of 90% Caco-2/10% HT29-MTX and 75% Caco-2/25%
      HT29-MTX, however, a mucus layer completely covered the cell monolayer and the in
      vitro digestion model was nearly as responsive to changes in sample iron
      bioavailability as pure Caco-2 cultures. The in vitro digestion/Caco-2 cell
      culture model correlates well with human iron bioavailability studies, but, as
      mucus appears to play a role in iron absorption, the addition of a
      physiologically realistic mucus layer and goblet-type cells to this model may
      give more accurate iron bioavailability predictions.

PMID- 18715774
TI  - Anoxic-aerobic treatment of the liquid fraction of cattle manure.
AB  - Cattle manure from a dairy farm was treated in order to reduce its pollution
      potential. The manure came from a farm with 120 cows kept in stables in a free
      stall barn. As pretreatment, the manure is usually filtered on the farm using a
      screw press separator with a 0.5 mm mesh. Approximately 70% of the total filtered
      volume passes through the screen, thus constituting the liquid fraction. This
      fraction, with a composition of around 64,500 mg COD/l, 5770 mg total-N/l and 800
      mg total-P/l, was subjected to centrifugation followed by a two-step biological
      treatment (anoxic-aerobic) to reduce organic matter (COD), nitrogen and
      phosphorus compounds. Centrifugation led to the following removal efficiencies:
      35% total solids, 60% COD, 75% total phosphorus and 20% total nitrogen (mainly
      organic nitrogen). With the subsequent anoxic-aerobic treatment, average removal
      efficiencies of 85% for COD, 90% for total phosphorus and 75% for total nitrogen
      were achieved.

PMID- 18715775
TI  - Comparative study on the characteristics of fly ash and bottom ash geopolymers.
AB  - This research was conducted to compare geopolymers made from fly ash and ground
      bottom ash. Sodium hydroxide (NaOH) and sodium silicate (Na(2)SiO(3)) solutions
      were used as activators. A mass ratio of 1.5 Na(2)SiO(3)/NaOH and three
      concentrations of NaOH (5, 10, and 15M) were used; the geopolymers were cured at
      65 degrees C for 48 h. A Fourier transform infrared spectrometer (FT-IR),
      differential scanning calorimeter (DSC), and scanning electron microscope (SEM)
      were used on the geopolymer pastes. Geopolymer mortars were also prepared in
      order to investigate compressive strength. The results show that both fly ash and
      bottom ash can be utilized as source materials for the production of geopolymers.
      The properties of the geopolymers are dependent on source materials and the NaOH
      concentration. Fly ash is more reactive and produces a higher degree of
      geopolymerization in comparison with bottom ash. The moderate NaOH concentration
      of 10 M is found to be suitable and gives fly ash and bottom ash geopolymer
      mortars with compressive strengths of 35 and 18 MPa.

PMID- 18715776
TI  - Highly sensitive oligonucleotide-based fluorometric detection of mercury(II) in
      aqueous media.
AB  - This paper describes a highly sensitive and selective Hg(2+) sensor using a label
      free Hg(2+) specific probe (5'-18T-3') and an intercalation dye SYBR Green I
      (SG). The Hg(2+) specific probe is composed of thymines (T) and readily forms T
      Hg(2+)-T complexes in the presence of Hg(2+). This specific T-Hg(2+)-T formation
      affects the hybridization of the Hg(2+) specific probe and the intercalation of
      SG. Upon treatment of 1 nM 5'-18T-3' with different amount of Hg(2+) (0.1-10nM),
      which is followed by hybridization with 1 nM 5'-18T-3' and incubation with 1
      microL of SG, the solution fluorescence gave a linear response (R=0.996) to the
      concentration of Hg(2+). The detection limit for Hg(2+) was 0.5 nM (0.1 ppb). The
      overall test only takes few minutes and very little interference is observed from
      non-specific metal ions. This approach may find potential applications in
      monitoring the Hg(2+) concentration in drinking water.

PMID- 18715777
TI  - Negative dielectrophoretic patterning with different cell types.
AB  - In this paper, a novel method for patterning different cell types based on
      negative dielectrophoresis (n-DEP), without any special pretreatment of a culture
      slide, has been described. An interdigitated array (IDA) electrode with four
      independent microelectrode subunits was fabricated with indium-tin-oxide (ITO)
      and used as a template to form cellular micropatterns. A suspension of C2C12
      cells was introduced into the patterning device between the upper slide and the
      bottom IDA. In the present system, the n-DEP force is induced by applying an ac
      voltage (typically 12V(pp), 1MHz) to direct cells toward a weaker region of
      electric field strength. The cells aligned above one of the bands of IDA within
      1min since the aligned areas on the slide were regions with the lower electric
      field. The application of an ac voltage for 5min allows the cells to adsorb onto
      the cell culture slide. After removing excess cells, the second cell type was
      patterned in lines using the same method as with the first set of cells. Periodic
      and alternate cell lines incorporating two cell types were also fabricated by
      changing the ac voltage mode. A second cell type was introduced into the device
      and guided to other areas to form a different pattern. The described system
      enables two cell types to be patterned in 15min. The patterning method provides a
      novel tool for use in fundamentals studies of cell biology based on cell-cell
      interactions between different cell types.

PMID- 18715778
TI  - Combining biological gene expression signatures in predicting outcome in breast
      cancer: An alternative to supervised classification.
AB  - INTRODUCTION: Gene expression profiling has been extensively used to predict
      outcome in breast cancer patients. We have previously reported on biological
      hypothesis-driven analysis of gene expression profiling data and we wished to
      extend this approach through the combinations of various gene signatures to
      improve the prediction of outcome in breast cancer. METHODS: We have used gene
      expression data (25.000 gene probes) from a previously published study of tumours
      from 295 early stage breast cancer patients from the Netherlands Cancer Institute
      using updated follow-up. Tumours were assigned to three prognostic groups using
      the previously reported Wound-response and hypoxia-response signatures, and the
      outcome in each of these subgroups was evaluated. RESULTS: We have assigned
      invasive breast carcinomas from 295 stages I and II breast cancer patients to
      three groups based on gene expression profiles subdivided by the wound-response
      signature (WS) and hypoxia-response signature (HS). These three groups are (1)
      quiescent WS/non-hypoxic HS; (2) activated WS/non-hypoxic HS or quiescent
      WS/hypoxic tumours and (3) activated WS/hypoxic HS. The overall survival at 15
      years for patients with tumours in groups 1, 2 and 3 are 79%, 59% and 27%,
      respectively. In multivariate analysis, this signature is not only independent of
      clinical and pathological risk factors; it is also the strongest predictor of
      outcome. Compared to a previously identified 70-gene prognosis profile, obtained
      with supervised classification, the combination of signatures performs roughly
      equally well and might have additional value in the ER-negative subgroup. In the
      subgroup of lymph node positive patients, the combination signature outperforms
      the 70-gene signature in multivariate analysis. In addition, in multivariate
      analysis, the WS/HS combination is a stronger predictor of outcome compared to
      the recently reported invasiveness gene signature combined with the WS.
      CONCLUSION: A combination of biological gene expression signatures can be used to
      identify a powerful and independent predictor for outcome in breast cancer
      patients.

PMID- 18715779
TI  - Potential roles for the PIM1 kinase in human cancer - a molecular and therapeutic
      appraisal.
AB  - In vitro experiments have shown the PIM1 kinase to have diverse biological roles
      in cell survival, proliferation and differentiation. In humans, PIM1 is often
      expressed in both normal and transformed cells. The PIM1 kinase is a true
      oncogene implicated in early transformation and tumour progression in
      haematopoietic malignancies and prostate carcinomas. It is associated with
      aggressive subgroups of lymphoma, is a marker of poor prognosis in prostate
      carcinomas and has been suggested to have a role in hormone insensitivity of
      prostate malignancies. PIM1 has a possible role in other carcinomas with 6p21
      genomic alterations. On one hand, PIM1 (due to its role in malignancy) appears to
      be a promising target for drug development programmes but, on the other hand, the
      complexity of its molecular structure has posed challenges in the development of
      PIM1 inhibitors. In this review we discuss PIM1 expression in human tissues
      (including some new data from our laboratory), its role in human malignancies, as
      well as the possibilities and challenges in the development of target therapy for
      PIM1.

PMID- 18715780
TI  - Helicobacter species are associated with possible increase in risk of
      hepatobiliary tract cancers.
AB  - BACKGROUND: Attempts at early identification of hepatobiliary cancers have failed
      due to non-availability of a sensitive test. Prevention offers the best chance to
      reduce the morbidity and mortality from these. Identification of an etiological
      agent and especially if the potentially identified cause can be eradicated like
      Helicobacter sp. infection, will not only reduce incidence but also the
      mortality. METHODS: This article reviews 15 studies on Helicobacter species in
      hepatobiliary cancers identified on pubmed, scopus and google scholar search. Of
      these, Five were single group and 10 were case control. These 10 case control
      studies were included in the meta analysis, which was carried out using odds
      ratio and both a fixed and random effect model, 95% confidence intervals for odds
      ratio was calculated. Chi square test for heterogeneity was employed. The overall
      effect was calculated using Z test. RESULTS: The cumulative sample size of cases
      was 205, of which 115 were positive (56%) for Helicobacter, while among 263
      controls 53 (20%) were found to be positive for Helicobacter infection. The
      positivity rate in case control studies was higher than that observed in single
      group studies. The cumulative odds ratio for the study sample was 8.72 (95% CI
      4.78-15.91) (Z=7.07; p<0.00001). CONCLUSIONS: There is enough evidence to suggest
      a possible role of Helicobacter species in hepatobiliary tract cancers. However,
      the results from different regions of the world differ. Studies also differ on
      method of Helicobacter detection, subsite of cancer with in the hepatobiliary
      tract and choice of controls thus introducing heterogeneity. Further case control
      studies with larger sample size are required to settle the question.

PMID- 18715781
TI  - PNA/DNA interstrand cross-links from a modified PNA base upon photolysis or
      oxidative conditions.
AB  - PNA/DNA interstrand cross-links (ICLs) were observed when peptide nucleic acids
      (PNAs) containing modified thymine derivatives were hybridized with the
      complementary or one-base mismatched DNA upon photolysis or treatments of
      oxidative agent. PNA/DNA ICL formation provides a useful method for biological
      applications such as antisense technologies or PNA chips.

PMID- 18715782
TI  - Design, synthesis, and bioactivity of putative tubulin ligands with adamantane
      core.
AB  - Several adamantane-based taxol mimetics were synthesized and found to be
      cytotoxic at micromolar concentrations and to cause tubulin aggregation. The
      extent of the aggregation is maximal for N-benzoyl-(2R,3S)
      phenylisoseryloxyadamantane (5) and is very sensitive to the structural
      modifications. A hybrid compound (15), combining adamantane-based taxol mimetic
      with colchicine was synthesized and found to possess both microtubule
      depolymerizing and microtubule bundling activities in A549 human lung carcinoma
      cells.

PMID- 18715783
TI  - Unravelling the tumor-suppressive functions of FOXO proteins.
AB  - Members of the forkhead box O (FOXO) family of transcription factors have been
      postulated to be tumor suppressors because of their established roles in cell
      cycle arrest, apoptosis, DNA-damage repair and scavenging of reactive oxygen
      species. Recently, several animal model studies have shown that the FOXO proteins
      are indeed tumor suppressors. Furthermore, FOXO proteins have recently been
      implicated in the negative regulation of signaling by the hypoxia-inducible
      factor 1 during vascular development, raising the possibility that the FOXO
      proteins suppress not only tumor formation but also tumor angiogenesis and,
      possibly, metastasis. Here, we discuss recent advances in the understanding of
      the roles of FOXO family members in tumor suppression.

PMID- 18715784
TI  - The importance of the twin-arginine translocation pathway for bacterial
      virulence.
AB  - The twin-arginine translocation (Tat) pathway is a prokaryotic transport system
      that enables the transport of folded proteins across the cytoplasmic membrane.
      The Tat pathway was originally thought to transport only proteins that bind
      cofactors in the cytoplasm and, thus, fold before transport, like many proteins
      related to energy metabolism. However, in recent years it has become clear that
      the Tat pathway has a broader role and is also an important virulence factor in
      different bacterial pathogens. Because the Tat pathway is well conserved among
      important bacterial pathogens and absent from mammalian cells, it could be a
      target for novel antimicrobial compounds. In this review, we highlight the
      importance of the Tat system for virulence in several human and plant pathogens.

PMID- 18715785
TI  - Salicylanilides: selective inhibitors of interleukin-12p40 production.
AB  - Interleukin (IL)-12p40, a subunit component of both IL-12 and IL-23, is being
      widely studied for its role in inflammatory disease. As part of an effort to
      profile cellular signaling pathways across different cell types, we report
      salicylanilide inhibitors of IL-12p40 production in stimulated dendritic cells.
      Based on a hypothesis that a desirable therapeutic profile is one that could
      block IL-12p40 but not IL-6 production, we engaged in directed analoging. This
      resulted in salicylanilides with similar IL-12p40 related potency but enhanced
      selectivity relative to IL-6 production.

PMID- 18715786
TI  - Design, synthesis, and antitumor activity of new bis-aminomethylnaphthalenes.
AB  - A new series of bis-aminomethylnaphthalenes were synthesized in satisfactory
      overall yield, through a simple synthetic strategy using reductive amination. The
      DNA binding properties of these compounds have been examined and compared to
      those of reference drugs using an UV spectroscopy method. The compounds were
      evaluated for their in vitro anticancer activity and some of them were studied in
      vivo. Compound 15 exhibited remarkable antitumor activity and represents a novel
      template for anticancer chemotherapy and can serve as a new lead compound.

PMID- 18715787
TI  - Synthesis and biological activity of 1-methyl-tryptophan-tirapazamine hybrids as
      hypoxia-targeting indoleamine 2,3-dioxygenase inhibitors.
AB  - We have designed and synthesized new hypoxic-neoplastic cells-targeted
      indoleamine 2,3-dioxygenase (IDO) inhibitors. 1-Methyl-tryptophan (1MT)
      tirapazamine (TPZ, 3-amino-1,2,4-benzotriazine 1,4-dioxide) hybrid inhibitors
      including 1 (TX-2236), 2 (TX-2235), 3 (TX-2228), and 4 (TX-2234) were prepared.
      All of these compounds were uncompetitive IDO inhibitors. TPZ-monoxide hybrids 1
      and 3 showed higher IDO inhibitory activities than TPZ hybrids 2 and 4. Among
      these hybrids, hybrid 1 was the most potent IDO inhibitor. TPZ hybrids 2 and 4
      showed stronger hypoxia-selective cytotoxicity than TPZ to EMT6/KU cells. These
      data suggest that TPZ hybrids 2 and 4 may act through their dual biological
      functions: first, they function as hypoxic cytotoxins in hypoxic cells, and then
      are metabolized to their TPZ-monoxide (3-amino-1,2,4-benzotriazine 1-oxide)
      hybrids, which function as IDO inhibitors.

PMID- 18715788
TI  - Molecular modeling studies toward the structural optimization of new cyclopeptide
      based HDAC inhibitors modeled on the natural product FR235222.
AB  - The natural cyclopeptide FR235222 is a potent HDAC inhibitor displaying relevant
      multiple anticancer effects and is considered an attractive lead compound for the
      generation of new and more effective antitumor therapeutics. Recently, we have
      synthesized a small collection of FR235222 simplified analogues which showed
      interesting biological activities. These results encouraged us to further explore
      the structural determinants responsible for the activity of this class of HDAC
      inhibitors in order to gain guidelines for the rational design of new derivatives
      with putative higher affinity for this target. In the present paper, we report
      the results obtained, docking these ligands in the binding pocket of HDLP, an
      HDAC homologue.

PMID- 18715789
TI  - Conjugates of the fungal cytotoxin illudin M with improved tumour specificity.
AB  - A simplified procedure for the isolation of gram quantities of illudin M from
      culture broths of basidiomycete Omphalotus olearius is described. Esters of
      illudin M with docosahexaenoic acid, chlorambucil, demethylcantharidinic acid
      (endothall) and 2,2'-bipyridyl-5,5'-dicarboxylic acid were synthesised and tested
      for cytotoxicity and induction of apoptosis in two clinically relevant tumour
      cell lines (Panc-1 pancreas carcinoma and HT-29 colon carcinoma) and in non
      malignant human foreskin fibroblasts. The demethylcantharidin and the bipyridine
      conjugates retained the cytotoxicity of the parent illudin M while displaying an
      improved specificity for the tumour cells over the fibroblasts.

PMID- 18715790
TI  - Determination of Cd and Cr in an ABS candidate reference material by instrumental
      neutron activation analysis.
AB  - In order to practically better cope with technical barriers to trade (TBT) of a
      great number of resin goods, our research presents first-ever results for the
      determination of Cd and Cr in acrylonitrile butadiene styrene (ABS) candidate
      reference material using instrumental neutron activation analysis (INAA) recently
      recognized as a candidate primary ratio method with a particular attention to the
      estimation of involved measurement uncertainties.

PMID- 18715791
TI  - A fully automated one-pot synthesis of [carbonyl-11C]WAY-100635 for clinical PET
      applications.
AB  - A fully automated synthesis of the important 5HT(1A) receptor radioligand,
      [carbonyl-(11)C]WAY-100635 (I), was developed based on the optimized one-pot
      "wet" synthesis procedure. A modern automated apparatus was constructed from
      commercially available components and operated via LabView software. In average,
      (906+/-525)MBq (n=94) of (I) was obtained from 40 min bombardment at 50 microA
      beam current within 50 min synthesis time. The specific radioactivity (SA) at the
      time of injection was (50.5+/-29.3)GBq/mumol (n=94).

PMID- 18715792
TI  - Is incidence of postoperative vasoplegic syndrome different between off-pump and
      on-pump coronary artery bypass grafting surgery?
AB  - OBJECTIVE: Postoperative vasoplegic syndrome (PVS) is a potentially lethal
      condition with increased mortality and other postoperative morbidities. Many
      previous studies have examined the outcomes associated with on-pump coronary
      artery bypass grafting (CABG) surgery, little is known about the incidence of PVS
      after off-pump CABG. METHODS: From November 21, 2005 to June 9, 2006, 334
      patients underwent isolated on-pump CABG and 362 had off-pump CABG surgery.
      Perioperative variables were retrospectively compared between on-pump and off
      pump CABG surgery using univariate analysis. Significant variables were included
      into a stepwise regression model to ascertain their independent impact on the
      incidence of PVS. RESULTS: The incidence of PVS in isolated on-pump CABG was
      6.9%; in off-pump CABG was 2.8% (p=0.01). However, in multivariable models
      adjusted for confounders, on-pump CABG did not reach statistical significance as
      a risk factor of PVS (OR=2.3, 95% CI 0.94-5.78; p=0.07). In on-pump CABG,
      preoperative left ventricular EF less than 35% (OR=3.6; p=0.02) and increased
      body mass index (OR=1.1; p=0.04) were identified as risk predictors of PVS;
      whereas elective surgery (OR=0.2; p=0.02) and preoperative use of beta-blockers
      (OR=0.21; p=0.02) were associated with a decreased rate of PVS. PVS was
      associated with longer ICU stay (OR=6.0; p<0.01), postoperative ventilation
      (OR=4.6; p<0.01), and hospital stay (OR=2.62; p=0.03). There was a stronger
      association between preoperative ACE inhibitors therapy and increased risk of PVS
      in off-pump CABG surgery (OR=4.52, 95% CI 0.95-21.67; p=0.06) than in on-pump
      CABG surgery (OR=1.06, 95% CI 0.35-3.19; p=0.91), but neither of them reaches
      statistical significance. CONCLUSIONS: The incidence of PVS after off-pump CABG
      surgery was significantly lower than after on-pump CABG surgery.

PMID- 18715794
TI  - Open chest after cardiac surgery; revisited.

PMID- 18715793
TI  - Real-time adjustment of ventricular restraint therapy in heart failure.
AB  - OBJECTIVE: Current ventricular restraint devices do not allow for either the
      measurement or adjustment of ventricular restraint level. Periodic adjustment of
      restraint level post-device implantation may improve therapeutic efficacy. We
      evaluated the feasibility of an adjustable quantitative ventricular restraint
      (QVR) technique utilizing a fluid-filled polyurethane epicardial balloon to
      measure and adjust restraint level post-implantation guided by physiologic
      parameters. METHODS: QVR balloons were implanted in nine ovine with post
      infarction dilated heart failure. Restraint level was defined by the maximum
      restraint pressure applied by the balloon to the epicardium at end-diastole. An
      access line connected the balloon lumen to a subcutaneous portacath to allow
      percutaneous access. Restraint level was adjusted while left ventricular (LV) end
      diastolic volume (EDV) and cardiac output was assessed with simultaneous
      transthoracic echocardiography. RESULTS: All nine ovine successfully underwent
      QVR balloon implantation. Post-implantation, restraint level could be measured
      percutaneously in real-time and dynamically adjusted by instillation and
      withdrawal of fluid from the balloon lumen. Using simultaneous echocardiography,
      restraint level could be adjusted based on LV EDV and cardiac output. After QVR
      therapy for 21 days, LV EDV decreased from 133+/-15 ml to 113+/-17 ml (p<0.05).
      CONCLUSION: QVR permits real-time measurement and physiologic adjustment of
      ventricular restraint therapy after device implantation.

PMID- 18715795
TI  - Surgical maneuvers for the management of bronchial complications in lung
      transplantation.
AB  - BACKGROUND: Many advances have substantially improved the clinical results of
      lung transplantation. However, the incidence of bronchial complications is still
      high, with significant impact on survival and limited interventional strategies
      for complex cases. Our aim is to evaluate the surgical management of bronchial
      complications following lung transplantation. METHODS: From May 1989 to June
      2007, 251 patients were submitted to lung transplantation at our institution. In
      five cases, the bronchial complications observed were dealt with open surgical
      procedures. RESULTS: Complications surgically dealt were one broncho-arterial
      fistula and four stenosis. One left upper sleeve lobectomy, one right upper
      sleeve lobectomy and three segmental bronchial resections with anastomosis were
      performed. In all five cases the surgical procedure was successful and optimal
      bronchial healing was observed. Three patients died due to causes unrelated to
      the bronchial anastomosis 5, 21 and 32 months after the bronchoplastic procedure.
      Two patients are still alive and functionally well at 52 and 70 months post
      bronchoplasty. CONCLUSIONS: Surgical management of bronchial complications after
      lung transplantation may be the last resort in complex, recalcitrant cases,
      nevertheless it is a feasible procedure and can provide good results not only on
      short- but also long-term follow-up.

PMID- 18715796
TI  - Management of asymptomatic patients with severe non-ischaemic mitral
      regurgitation. Are practices consistent with guidelines?
AB  - OBJECTIVE: For asymptomatic patients with severe mitral regurgitation, guidelines
      recommend surgery in selected patients. However, little is known on how the
      current practice fits with guidelines. METHODS: Of the 5001 patients
      prospectively included in the Euro Heart Survey on valvular heart disease, 877
      had isolated mitral regurgitation and 546 had severe mitral regurgitation (grade
      >or=3/4 with Doppler echocardiography). Of them, 101 were asymptomatic and had
      non-ischaemic mitral regurgitation. The decision to refer the patients to surgery
      or not operate was analysed by comparing patient characteristics with American
      College of Cardiology/American Heart Association guidelines. RESULTS: Coronary
      angiography was performed in 21 out of 33 patients (64%) who were considered for
      surgery. Catheterisation was performed in 27 patients (27%). A decision to
      operate was taken in 33 patients (33%). Decisions to refer to surgery or not were
      in accordance with guidelines in 63 patients (62%). Regarding discordant
      decisions, intervention was considered 'over-used' in 9 patients (9%) and 'under
      used' in 29 patients (29%), of whom 24 had a class I or IIa indication for
      surgery. Of the 68 non-operated patients, 44 (65%) received at least one drug
      with haemodynamic effect. CONCLUSIONS: In asymptomatic patients with severe
      mitral regurgitation, preoperative coronary angiography seems under-used and
      cardiac catheterisation is frequently used. Regarding the decision to operate or
      not, a large number of patients were not referred to surgery even though they
      fulfilled recommendation for surgery. Thus, to avoid too late surgical referral,
      implementation of existing guidelines should be improved.

PMID- 18715797
TI  - Cough-induced rib fracture and diaphragmatic rupture resulting in simultaneous
      abdominal visceral herniation into the left hemithorax and subcutaneously.
AB  - Violent coughing is associated with a multitude of complications including rib
      fractures and diaphragmatic rupture. In this report we present a case of a 70
      year-old male with the rare combination of both complications resulting in
      herniation of bowel into the left hemithorax and subcutaneously between the
      separated ribs. Surgical repair was performed via a left thoracotomy, the hernia
      reduced and the diaphragmatic and chest wall defect repaired primarily with
      excellent patient recovery and relief of symptoms.

PMID- 18715798
TI  - Complement activation cascade and its regulation: relevance for the response of
      solid tumors to photodynamic therapy.
AB  - The complement system has emerged as a prominent participant in host response
      elicited following treatment of solid tumors by photodynamic therapy (PDT).
      Activity of the complement system is tightly controlled by a series of endogenous
      regulatory proteins. The expression of decay-accelerating factor (DAF),
      complement-receptor-1-related protein y (Crry), and protectin, which are the
      three major mouse membrane-bound complement regulatory proteins (mCRPs), was
      examined following treatment of murine squamous cell carcinomas SCCVII by PDT
      mediated by the photosensitizer Photofrin. A marked decrease was detected in the
      expression of all three mCRPs on cancer cells from tumors following PDT,
      indicating that these cells were made more vulnerable to complement attack. In
      order to amplify this effect, following PDT mice were injected with antibodies
      neutralizing either Crry, protectin, or DAF. With anti-Crry and anti-protectin
      this resulted in increased tumor cure rate compared to PDT alone, while the
      contrary was observed with PDT plus anti-DAF combination (presumably owing to
      additional role of DAF in T cell signaling). Further examination including other
      complement regulatory proteins showed that combining antitumor PDT with antibody
      mediated neutralization of factor H (soluble negative complement regulator) or
      injection of properdin (positive complement regulator) increased the cure rates
      of PDT-treated tumors. The use of various agents promoting complement activity
      appears promising for employment as adjuvants to PDT.

PMID- 18715799
TI  - The microbial and danger signals that activate Nod-like receptors.
AB  - Nod-like receptors (NLRs) are a family of intracellular sensors that play key
      roles in innate immunity and inflammation. While some NLRs, including Nod1, Nod2,
      NAIP and IPAF, detect conserved bacterial molecular signatures from within the
      host cytosol, other members of this family seem to have evolved the capacity to
      sense danger signals perhaps independently of a microbial trigger. This is
      illustrated by the discovery that Nalp3 and Nalp1 are specifically activated by
      low concentrations of intracellular potassium. The fact that several stimuli,
      including bacterial toxins and some viruses, but also sterile crystals made of
      uric acid, asbestos or aluminium hydroxide, can trigger the Nalp3 inflammasome
      illustrate the fascinating prospect that microbial infections and certain danger
      signals may be perceived similarly by host recognition systems. Gaining insight
      into the function of NLR proteins in general will impact considerably on our
      understanding of the mechanisms underlying immunity to infection, adjuvanticity
      and auto-inflammatory disorders. In this review, we summarize the current
      knowledge on the microbial- and danger-derived signals that activate NLRs.

PMID- 18715800
TI  - Phoenix Mars Mission--the thermal evolved gas analyzer.
AB  - The Phoenix spacecraft that was launched to Mars in August 2007 landed safely on
      the Martian northern arctic region on May 25, 2008. It carried six experiments to
      study the history of water on the planet and search for organic molecules in the
      icy subsurface Martian soil. The spacecraft is a lander with an arm and scoop
      designed to dig a trench though the top soil to reach an expected ice layer near
      the surface. One of the instruments on board is the thermal evolved gas analyzer
      (TEGA), which consists of two components, a set of eight very small ovens that
      will heat samples of the ice soil mixtures from the trench to release imbedded
      gases and mineral decomposition products, and a mass spectrometer that serves as
      the analysis tool for the evolved gases, and also for measurements of the
      composition and isotopic ratios of the gases that comprise the atmosphere of
      Mars. The mass spectrometer is a miniature magnetic sector instrument controlled
      by microprocessor-driven power supplies. One feature is the gas enrichment cell
      that will increase the partial pressures of the noble gases in an atmosphere
      sample by removing all the active gases, carbon dioxide, and nitrogen, to improve
      the accuracy of their isotopic ratio measurements.

PMID- 18715801
TI  - "It is the antigen(s), stupid" and other lessons from over a decade of
      vaccitherapy of human cancer.
AB  - The lessons are: (a) human cancers certainly respond to immunological
      manipulations. Efforts at human cancer immunotherapy are therefore worthwhile.
      (b) Prophylaxis is very different from therapy of pre-existing disease, and hence
      much enthusiasm should not be derived from successful prophylaxis studies. Even
      in case of infectious agents against which robust prophylaxis is routinely
      achieved, therapy is nearly impossible once the disease has established. (c)
      Studies with appropriate cancer models of mice and rats are useful. The notion
      that it is easy to cure cancers in mice is generally advanced the most
      confidently by those who have never cured a mouse of cancer by immunotherapy. (d)
      With a nod to James Carville, it is the antigen(s), stupid! We still do not know
      the identity of protective tumor antigens. If any lesson can be drawn at all, it
      may well be that cancer immunotherapy must move away from the one-shoe-fits-all
      therapeutic models of chemotherapy and must move to individualized approaches.
      (e) All targets are equal, but some are more equal than others. The key is
      specificity for cancer. That does not necessarily mean specificity for cancer
      cells. (f) Vaccitherapy must be attempted preferably in the minimal residual
      disease setting, even though this is certain to be time-taking and expensive. In
      the setting of bulky disease, vaccitherapy must be combined with blockade of
      inhibitory signals, or depletion of down-regulatory T cells. Inhibition of
      effector level suppression of immune response is a key. Vaccitherapy alone or
      immuno-modulation alone is unlikely to succeed in therapy of bulky metastatic
      disease.

PMID- 18715802
TI  - Regulation of CD8(+) T cell functions by RARgamma.
AB  - Retinoic acid plays a key role in the development and function of the immune
      system; however, the contribution of each of the three retinoic acid receptors
      (RARs) to the T cell immune response is not yet well understood. Of these
      receptors, both RARalpha and RARgamma are expressed in T lymphocytes. While
      possible functional redundancy thus complicates understanding of the role of each
      receptor in T cells, emerging data suggest that RARalpha and RARgamma function
      differently in thymocyte development and that RARgamma is required for both
      primary and secondary CD8(+) T cell immune responses.

PMID- 18715803
TI  - NEW technologies for meeting the global demand for pandemic influenza vaccines.
AB  - A new influenza pandemic is expected and if caused by the H5N1 virus it could be
      severe. Antiviral agents will be unavailable to most people and vaccines are
      regarded as the mainstay of protection. Development of inactivated H5N1 vaccines
      has been slow because of reluctance by US regulatory authorities to consider
      adjuvanted formulations and the unwillingness of Western European governments to
      fund vaccine trials. With effective political leadership, large amounts of live
      attenuated and recombinant hemagglutinin pandemic vaccines could be produced
      quickly in existing facilities using egg-based technologies. New types of
      influenza vaccines, new technologies for their production and new adjuvants to
      make them more immunogenic are receiving the attention of scientists and vaccine
      developers. These technologies could help meet the global demand for pandemic
      vaccines, but only if they are coupled with improvements in the human
      infrastructure necessary for pandemic vaccination.

PMID- 18715805
TI  - Relationship between density variability and imaging volume size in cone-beam
      computerized tomographic scanning of the maxillofacial region: an in vitro study.
AB  - OBJECTIVE: In limited-volume cone-beam computerized tomography (CBCT) imaging,
      projection data discontinuity caused by maxillofacial hard tissue structures
      outside the reconstructed volume are reported to affect the density value of the
      hard and soft tissue structures within the volume. The intensity of this effect
      is purported to be related to the size of the imaging volume. The aim of this
      study was to characterize the effect of the size of the scanned volume on density
      values in vitro. STUDY DESIGN: Test objects were positioned in a custom phantom
      in the following 4 patterns: bimandible and vertebrae, bimandible, left mandible
      and vertebrae, and left mandible. We used a newly developed flat panel detector
      CBCT system (Alphard Vega; Asahi Roentgen, Kyoto, Japan) to acquire scans of the
      left molar region using cylindrical volumes of approximately 5, 10, 15, and 20 cm
      in diameter and height. The density values of the mandible and the adjacent soft
      tissue regions were analyzed. RESULTS: Highest density variability was observed
      in the smallest-volume (5 cm) scans. Density variability increased when more
      objects were included outside the area being imaged. Fewer effects were noted in
      CBCT scans of larger (10, 15, and 20 cm) volumes. CONCLUSION: Larger-volume CBCT
      scans may yield more consistent density values. Smaller CBCT volumes have the
      advantages of better image resolution and lower radiation doses. The optimization
      of the image characteristics is maximized by careful consideration of the purpose
      of the CBCT examination.

PMID- 18715806
TI  - Circulating angiogenic monocyte progenitor cells are reduced in JAK2V617F high
      allele burden myeloproliferative disorders.
AB  - The clinical course of patients with Philadelphia chromosome negative
      myeloproliferative disorder is frequently complicated by thrombotic events. Post
      natal vasculogenesis has been proposed to play a critical role in angiogenesis by
      acting through a hierarchy of endothelial progenitor cells. Some endothelial
      progenitor cells have been shown to share a number of features associated with
      monocytes while other more primitive progenitor cells produce endothelial cells
      in vitro exclusively. The cells which share features of monocytes and endothelial
      cells have been termed angiogenic monocytes. Reduced levels of angiogenic
      monocyte progenitor cells have been reported to be predictive of atherosclerotic
      disease progression. Angiogenic monocyte progenitor cells were assayed in vitro
      from the peripheral blood mononuclear cells of myeloproliferative disorder
      patients. Angiogenic monocyte colonies were plucked and analyzed for endothelial
      cells and hematopoietic cell markers, JAK2V617F and their ability to incorporate
      into vascular endothelium following their transplantation into non-obese
      diabetic, severe combine immunodeficient mice. Myeloproliferative disorder
      angiogenic monocyte colonies that were detected were uniformly JAK2V617F positive
      and produced cells that expressed phenotypic markers characteristic of both
      monocytes and endothelial cells. Reduced numbers of angiogenic monocyte colonies
      were present in the blood of myeloproliferative disorder patients with a high
      JAK2V617F burden (>50%), (p<0.01). Transplanted angiogenic monocytes were able to
      contribute to the vascular endothelium of non-obese diabetic, severe combine
      immunodeficient mice. These studies suggest that reduced numbers of circulating
      angiogenic monocyte progenitors contribute to the propensity to develop
      thrombotic complications in myeloproliferative disorder patients.

PMID- 18715807
TI  - A study of the prevalence and genotypes of Giardia duodenalis infecting kennelled
      dogs.
AB  - Giardia duodenalis is a protozoan parasite of animals that is zoonotic. Given the
      capacity of this organism to spread via the faecal-oral route, animals held in
      overcrowded and unhygienic conditions are at high risk of infection. Faecal
      samples from dogs in three kennels in Rome were examined by microscopy and PCR
      for G. duodenalis, and the prevalence data generated were correlated with
      variables such as kennel identity, age of dog, length of time the dog had been
      kennelled and clinical signs. The overall prevalence of the parasite in the
      faecal samples was 20.5% and was higher in samples from the largest kennel, which
      had the greatest turnover of dogs, and in faecal samples from younger animals.
      Giardia cysts were found more frequently in diarrhoeic animals but were also
      found in dogs with no clinical signs. Although the finding that the majority of
      isolates were dog-specific rather than zoonotic genotypes suggests that the
      zoonotic risk from this pathogen is less than previously thought, the higher
      prevalence of infection in younger dogs may pose a specific public health issue
      as such animals are more frequently re-homed with families.

PMID- 18715808
TI  - Precision of the XCT 3000 and comparison of densitometric measurements in distal
      radius scans between XCT 3000 and XCT 2000 peripheral quantitative computed
      tomography scanners.
AB  - Researchers conducting longitudinal studies face challenges as technology evolves
      and data collection equipment is upgraded from older to newer models. In this
      study, we report precision error and associations from correlation, regression
      equations, and Bland-Altman plots that compare results of distal radius images
      from the XCT 2000 and XCT 3000 peripheral quantitative computed tomography
      densitometers at the 4% and 20% distal radius site. The mean difference expressed
      as a percent of the measurement's mean was approximately 5% for cortical
      thickness, periosteal and endosteal circumferences, and total bone size at the
      20% site, and less than 2% for all other measures. There were strong associations
      between bone parameter measures from the XCT 3000 and XCT 2000 with correlation
      coefficients ranging from 0.92 to 1.0. Strong associations between the 2 machines
      allow for the comparison of results with minor adjustments.

PMID- 18715809
TI  - The relationship between dual energy X-ray absorptiometry (DXA) and DXA with
      laser (DXL) measurements in children.
AB  - The present study was designed to examine the relationship between bone mineral
      density (BMD) measurements performed using conventional dual energy X-ray
      absorptiometry (DXA) in total body (TB), spine, and hip and the more recent
      technique of DXA with laser (DXL) in the calcaneus in a young population and to
      explore the diagnostic capacity of the heel DXL. One hundred and twelve persons,
      2.2-20.6yr of age, were studied using the 2 techniques. Significant correlations
      were observed between the heel BMD and BMD values in TB (r=0.73, p<0.001),
      TB(head excluded(HE)) (r=0.83, p<0.001), spine (r=0.72, p<0.001), and hip
      (r=0.90, p<0.001). The relationships between DXA and DXL measurements with 95%
      tolerance intervals are presented. Using heel DXL measurements to predict the
      lowest DXA quartiles at all the other measured sites revealed sensitivity levels
      of 0.9 (TB, spine, hip) and 1.0 (TB(HE)) and specificity levels of 0.86 (TB),
      0.94 (TB(HE)), 0.92 (spine), and 0.95 (hip). We conclude that BMD values obtained
      with DXA and DXL correlate well and that the DXA and DXL techniques effectively
      identify the same individuals with low BMD. The DXL, which is portable, easy to
      use and gives a low radiation dose, can be useful for assessing bone mass in a
      young population.

PMID- 18715810
TI  - Staging and prognosis in head and neck cancer.
AB  - Head and neck malignant tumors are classified according to the TNM staging
      system. The TNM system is a universally accepted, widely used, staging method.
      Its goals are to help clinicians and researchers to choose from treatment
      options, to give patients an estimate of their prognosis and to compare results
      of treatment. In this paper we discuss the history and daily usage of the TNM
      system and some pros and cons. In the field of prognostic estimations,
      particularly for the individual patient, the TNM system could be upgraded with
      other prognostic indicators. We discuss insights into enhanced usage of the TNM
      system and the possibilities of comprehensive and dynamic staging models.

PMID- 18715811
TI  - Expression of Bcl-2 family proteins and associated clinicopathologic factors
      predict survival outcome in patients with oral squamous cell carcinoma.
AB  - The aims of this study were to assess the expression levels of three proteins
      involved in apoptosis--Bcl-2, Bcl-X, and Bax--and evaluate their relationship
      with clinicopathologic features and survival in oral squamous cell carcinoma
      (OSCC). Immunohistochemistry was used to evaluate protein expression in 53
      primary OSCCs treated by radical surgery with free margins at a single
      institution in 1999. Histologic specimens were graded and analyzed for perineural
      invasion, lymphocytic infiltrate, and pattern of invasion. Digital image analysis
      was performed to quantify immunostaining. Survival was analyzed using the Kaplan
      Meier method and Cox's proportional hazard model. Cancer-specific 5-year survival
      (CSS) was 61% (56% overall survival (OS), and 51% disease-free interval (DFI)).
      Kaplan-Meier analysis identified pathologic stage (p=0.0007, log-rank test, OS),
      negative nodes status (pN) (p<0.0001, log-rank test, OS), presence of lymphocytic
      infiltrate (p=0.0084, log-rank test, OS), and high Bax expression (p=0.025, log
      rank test, OS) to each be associated with both better OS and CSS. Tongue tumors
      (p=0.0179, log-rank test), worst pattern of invasion (p=0.0293, log-rank test),
      lack of lymphocytic infiltrate (p=0.0328, log-rank test), perineural invasion
      (p=0.0448, log-rank test), poorly differentiated tumors (p=0.0318, log-rank
      test), and low Bcl-X expression (p=0.044, log-rank test) were all associated with
      a low DFI. Cox regression found pN, lymphocytic infiltrate, and Bax expression to
      be independent prognostic factors for OS and CSS, whereas lymphocytic response
      and tongue tumors were predictors of DFI. Bcl-2 expression emerged as an
      independent marker of favorable CSS. Lymphocytic infiltrate was the most
      meaningful histopathologic parameter in survival analysis, whereas expression of
      Bcl-2 family members seems to be an important marker of a favorable prognosis in
      OSCC.

PMID- 18715812
TI  - Current concepts for the management of head and neck cancer: chemotherapy.
AB  - Chemotherapy can be administered in patients with locoregionally advanced (LA)
      squamous cell carcinoma of the head and neck (SCCHN) either concurrently with
      irradiation or as induction chemotherapy prior to local treatment or as
      palliative therapy in patients with recurrent and/or metastatic disease.
      Cisplatin-based chemoradiation is still the standard for LA-SCCHN. TPF has
      emerged as the new standard regimen when induction chemotherapy is indicated.
      Areas of active investigation in LA-SCCHN are the sequential administration of
      induction chemotherapy followed by chemoradiation and the integration of targeted
      therapies. None of the combination chemotherapy regimens demonstrated an overall
      survival benefit when compared to single agent methotrexate, cisplatin or 5
      fluorouracil in recurrent/metastatic disease. Combination chemotherapy in this
      setting is preferably used in younger patients with a good performance status and
      with symptomatic disease who require prompt symptom relief. However, a survival
      benefit was observed when cetuximab was combined with platinum-5-fluorouracil.

PMID- 18715813
TI  - Osteonecrosis of the jaws in intravenous bisphosphonate use: Proposal for a
      modification of the clinical classification.

PMID- 18715814
TI  - Conditional survival rates of buccal and tongue cancer patients: how far does the
      benefit go?
AB  - The purpose of this study was to investigate the conditional survival probability
      in buccal and tongue cancer patients, and to identify the limit of increment in
      conditional survival probabilities after first diagnosis. This study
      retrospectively analyzed 339 consecutive patients with either buccal or tongue
      caner. The conditional survival probability was computed by Kaplan-Meier
      estimates, and the pair-wise Log-rank tests with Bonferroni correction were used
      to evaluate differences among conditional survival curves. It was found that the
      3-year conditional survival rates for successive years of survival were 55.5%,
      69.9%, 74.1% and 77.8%. The conditional survival curves started to become
      significantly better than the original survival curve at the twelfth month, and
      those curves after 24 months of survival were not significantly different from
      each other. Many previous studies have described the benefit of conditional
      survival probabilities for personalized information on better chance of survival,
      but only reported conditional survival probabilities and statistical tests for
      point-wise estimates. In this study, a new approach was adopted to conclude that
      the idea of conditional survival probability is best for the first 2 years in
      buccal and tongue cancer patients, and any longer survival time would not make
      significant difference in survival rates. The idea of pair-wise log-rank tests on
      conditional survival curves can provide statistical evidence for the critical
      time frame of survival in many different cancers.

PMID- 18715815
TI  - Detection of LINE-1s hypomethylation in oral rinses of oral squamous cell
      carcinoma patients.
AB  - This study aimed to (i) investigate long interspersed nuclear element-1 (LINE-1)
      methylation levels of oral squamous cell carcinomas (OSCCs), the major type of
      oral malignancies; and (ii) investigate whether the hypomethylation of LINE-1s
      can be detected in oral rinses of OSCC patients. The combined bisulfite
      restriction analysis polymerase chain reaction (PCR) of LINE-1s (COBRALINE-1) was
      used. We found that tissues from OSCC specimens had lower methylation levels of
      LINE-1s than cells collected from the oral rinses of normal volunteers.
      Interestingly, cells collected from oral rinses of OSCC patients also revealed
      hypomethylated LINE-1s at the same level as OSCC tissues. There was no difference
      in the level of hypomethylation due to stages, locations, histological grades,
      and history of betel chewing, smoking and/or alcohol consumption. In conclusion,
      OSCCs possessed global hypomethylation and this alteration could be detected from
      oral rinses of OSCC patients by a simple PCR technique, COBRALINE-1. Therefore,
      COBRALINE-1 of oral rinses may be applied for non-invasive detection of oral
      malignancies.

PMID- 18715816
TI  - Apoptotic effect of CKD-602 (Camtobell) on oral squamous cell carcinoma cell
      lines.
AB  - The purposes of this study were to measure the cytotoxic effect of CKD-602 on
      oral squamous cell carcinoma (OSCC) cell lines, to evaluate the apoptotic aspect
      of dead cells, and to identify the signaling molecules involved in apoptosis. The
      human OSCC cell lines A253, HSC-3 and KB were treated with CKD-602. The apoptotic
      proportion of the cells was analyzed using flow cytometry. The expression of Bax,
      Bcl-2, and p53 were detected by western blotting analysis. CKD-602 showed
      excellent cytotoxicity to the OSCC cell lines. Most cell death was attributed to
      apoptosis rather than necrosis. CKD-602 induced the down-regulation of Bcl-2 in
      A253 and HSC-3 cells, and p53 was expressed in the KB cell line after treatment
      with CKD-602.

PMID- 18715817
TI  - beta- and gamma-catenin expression in oral dysplasia.
AB  - Cell-cell and cell-matrix interactions regulate important cellular functions;
      they involve a number of specialised molecules and the corresponding receptors,
      among which a key role is played by cadherins and the associated catenins.
      Deregulation of these molecules has been associated with tumour progression in
      many human malignancies. While catenins expression has been extensively studied
      in many human cancers, including oral carcinoma (OSCC), less is known about their
      expression in oral epithelial dysplasia. The objective of this study was to
      evaluate the expression of these proteins in a large group of displastic lesions
      of the oral mucosa and their relation with subsequent malignant transformation.
      Expression of beta- and gamma-catenin was investigated by immunohistochemistry
      using specific monoclonal antibodies in 49 cases of oral epithelial dysplasia and
      10 samples of normal oral mucosa. The presence and absence of beta- and gamma
      catenin staining was expressed differently in relation to dysplasia grade; while
      the degree of dysplasia became more severe, we observed a statistically
      significant loss and/or reduction of catenins expression, the loss of the
      exclusive membranous expression and a cytoplasmic delocalisation. Progression to
      OSCC occurred in 10 out of our 49 cases (20.4%); all of them, except one, showed
      a concurrent and concordantly located beta- and gamma-catenin staining even, if
      no statistically significant differences were found between cases progressed to
      invasive OSCC or not. Catenins physiology alterations may be involved in the
      transformation process; however, the role of catenins expression as possible
      prognostic markers in precancerous oral lesions seems to be limited. Nonetheless,
      further studies on larger series of samples are necessary in order to clarify the
      role of catenins expression in oral carcinogenesis from both a biological and
      clinical point of view.

PMID- 18715818
TI  - FDG-PET and detection of distant metastases and simultaneous tumors in head and
      neck squamous cell carcinoma: a comparison with chest radiography and chest CT.
AB  - Detection of distant metastases and second primary tumors in patients with head
      and neck squamous cell carcinoma (HNSCC) is of importance because of the impact
      on treatment and prognosis. The aim of this study was to assess the value of
      whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET) in detecting
      distant metastases and second primary tumors below clavicular level in HNSCC
      compared to chest CT and chest radiography (CXR). Patient records of 149
      consecutive patients with a primary HNSCC in whom a whole-body FDG-PET for
      initial staging was performed were reviewed. FDG-PET showed a sensitivity and
      specificity for detecting distant disease of 92% and 93%, respectively. Chest CT
      (n=82) showed a sensitivity and a specificity of 74% and 61% respectively. CXR
      (n=106) showed a sensitivity and a specificity of 41% and 91%, respectively. FDG
      PET was shown to be able to detect distant metastases and second primary tumors
      in HNSCC with a high sensitivity and specificity. The higher sensitivity of PET
      compared to chest CT is mainly due to the detection of extrapulmonary malignancy.
      Sensitivity of PET and CT were similar in detecting intrapulmonary malignancy,
      but PET specificity was significantly higher. FDG-PET helps to determine the
      nature of pulmonary lesions and might be considered as a first diagnostic
      modality for detecting distant disease in advanced HNSCC.

PMID- 18715819
TI  - Bony changes in the jaws of rats treated with zoledronic acid and dexamethasone
      before dental extractions mimic bisphosphonate-related osteonecrosis in cancer
      patients.
AB  - Osteonecrosis of the jaw is associated with aminobisphosphonate use in patients
      treated with intravenous doses for the prevention of bony metastases. A more
      complete understanding of the natural history of bisphosphonate-related
      osteonecrosis of the jaws (BRONJ), factors associated with risk, and its
      pathobiology has been limited by the availability of human material and the
      absence of clinical predictability. We now describe an animal model, developed in
      female Sprague-Dawley rats, in which we replicate many of the clinical,
      radiographic, and histologic features described in humans. Animals treated with a
      sequence of zoledronic acid (ZA) and dexamethosone (DX) over a one to three week
      period developed BRONJ-like changes following extraction of mandibular or
      maxillary molars. Whereas the extraction sites of control animals underwent
      predictable healing with rapid epithelialization, animals treated with ZA/DX
      demonstrated clinical and histological evidence of ulceration overlying areas of
      necrotic bone. In contrast to images from control animals, radiographs from
      animals treated with ZA/DX demonstrated poor definition of the alveolar ridge
      with mixed radiodensity. Modest increases in the extent of the inflammatory
      infiltrate were seen fourteen days after extraction in ZA-only treated animals
      compared to control or ZA/DX-treated rats. However, by post-extraction day 28, no
      differences were observed. Tissue vascularity was most pronounced in ZA-only
      treated animals compared to ZA/DX or control specimens. Apoptosis of epithelial
      cells was not observed in any experimental groups, and no evidence of Actinomyces
      was observed as determined by Periodic Acid Schiff (PAS) staining. The
      administration of ZA/DX preceding dental extractions in rats therefore results in
      the development of bony and soft tissue changes that are similar to those noted
      humans who develop BRONJ, and may provide a useful model for study of its
      pathogenesis, as well as strategies for its prevention and treatment.

PMID- 18715820
TI  - A fluorescent probe for zinc ions based on N-methyltetraphenylporphine with high
      selectivity.
AB  - N-methyl-alpha,beta,gamma,delta-tetraphenylporphine (NMTPPH) has been used to
      detect trace amount of zinc ions in ethanol-water solution by fluorescence
      spectroscopy. The fluorescent probe undergoes a fluorescent emission intensity
      enhancement upon binding to zinc ions in EtOH/H(2)O (1:1, v/v) solution. The
      fluorescence enhancement of NMTPPH is attributed to the 1:1 complex formation
      between NMTPPH and Zn(II) which has been utilized as the basis for the selective
      detection of Zn(II). The linear response range covers a concentration range of
      Zn(II) from 5.0x10(-7) to 1.0x10(-5)mol/L and the detection limit is 1.5x10(
      7)mol/L. The fluorescent probe exhibits high selectivity over other common metal
      ions except for Cu(II).

PMID- 18715821
TI  - Spectroscopic, quantum chemical DFT/HF study and synthesis of [2.2.1] hept-2'-en
      2'-amino-N-azatricyclo [3.2.1.0(2,4)] octane.
AB  - The compound 4-N-bicyclo [2.2.1] hept-2'-en-2'-amino-N-azatricyclo [3.2.1.0(2,4)]
      octane (2) has been synthesized and characterized by elemental analysis, IR, UV
      vis, mass and NMR. Density functional theory (DFT) and Hartree-Fock (HF)
      calculations have been carried out for the title compound by using the standard 6
      31G* basis set. The calculated results show that the predicted geometry can well
      reproduce the structural parameters. Predicted vibrational frequencies have been
      assigned and compared with experimental IR spectra and they complement each
      other. The theoretical electronic absorption spectra have been calculated by
      using CIS, TD-DFT and ZINDO methods. The (13)C NMR and (1)H NMR of compound (2)
      have been calculated by means of Becke 3-Lee-Yang-Parr (B3LYP) density functional
      method with 6-31G* basis set. Comparison between the experimental and the
      theoretical results indicates that density functional B3LYP method is able to
      provide satisfactory results for predicting NMR properties. On the basis of
      vibrational analyses, the thermodynamic properties of the title compound at
      different temperatures have been calculated.

PMID- 18715822
TI  - Geometries and electronic properties of carbon-nitrogen clusters C8N4 and C8N4+/
      .
AB  - The geometry optimization and frequency analysis for the low-lying electronic
      states of C(8)N(4) and its ions are performed at the DFT/6-31G(d) level. Their
      energies are calibrated at the CCSD(T)/6-31G(d) level of theory. Ionization
      energy, electron affinity, binding energy of C(8)N(4), and anion photoelectron
      spectra of C(8)N(4)(-) are provided at the CCSD(T)/6-31G(d) level. Mulliken
      populations, leading configurations, bond orders, and compositions of molecular
      orbitals are used to examine the bonding characteristics in the low-lying
      electronic states of C(8)N(4) and its ions. It is surprising to find that the
      ground state of C(8)N(4) is the open shell (5)A(1) state. Interestingly for the
      low-lying electronic states of C(8)N(4) and its ions, their structures
      significantly corrugated, which may be caused by their larger [N]/([N]+[C])
      ratios. In addition, the similarities and differences between C(8)N(4) and
      C(10)N(2)(II) are analyzed and discussed.

PMID- 18715823
TI  - Spectrometric and voltammetric studies of the interaction between quercetin and
      bovine serum albumin using warfarin as site marker with the aid of chemometrics.
AB  - The interaction of quercetin, which is a bioflavonoid, with bovine serum albumin
      (BSA) was investigated under pseudo-physiological conditions by the application
      of UV-vis spectrometry, spectrofluorimetry and cyclic voltammetry (CV). These
      studies indicated a cooperative interaction between the quercetin-BSA complex and
      warfarin, which produced a ternary complex, quercetin-BSA-warfarin. It was found
      that both quercetin and warfarin were located in site I. However, the spectra of
      these three components overlapped and the chemometrics method - multivariate
      curve resolution-alternating least squares (MCR-ALS) was applied to resolve the
      spectra. The resolved spectra of quercetin-BSA and warfarin agreed well with
      their measured spectra, and importantly, the spectrum of the quercetin-BSA
      warfarin complex was extracted. These results allowed the rationalization of the
      behaviour of the overlapping spectra. At lower concentrations ([warfarin]<1x10(
      5) mol L(-1)), most of the site marker reacted with the quercetin-BSA, but free
      warfarin was present at higher concentrations. Interestingly, the ratio between
      quercetin-BSA and warfarin was found to be 1:2, suggesting a quercetin-BSA
      (warfarin)(2) complex, and the estimated equilibrium constant was 1.4x10(11)M(
      2). The results suggest that at low concentrations, warfarin binds at the high
      affinity sites (HAS), while low-affinity binding sites (LAS) are occupied at
      higher concentrations.

PMID- 18715824
TI  - Quenching effect of nickel ions on fluorescent gold nanoparticles.
AB  - Herein, we reported the quenching effect of Ni(2+) on bovine serum albumin
      protected fluorescent gold nanoparticles (BSA-GNPs). The quenching mechanism was
      discussed and a static quenching mechanism was proposed. The number of binding
      sites (n), apparent stability constants (K) and corresponding thermodynamic
      parameters of BSA-GNPs-Ni(2+) complex were measured at different temperatures.
      Under optimum conditions, the fluorescence intensity of BSA-GNPs is linearly
      proportional to nickel concentration from 6.0x10(-8)mol/L to 8.0x10(-6)mol/L with
      a detection limit of 1.0x10(-8)mol/L. The result indicated that BSA-GNP was a
      potential Ni(2+) probe.

PMID- 18715825
TI  - Scaled quantum chemical studies on the vibrational spectra of 4-bromo
      benzonitrile.
AB  - The vibrational spectra of 4-bromo benzonitrile have been reported. The
      fundamental vibrational frequencies and intensity of vibrational bands were
      evaluated using density functional theory (DFT) with the standard B3LYP/6-311+G
      basis set combination and were scaled using various scale factors which yielded a
      good agreement between observed and calculated frequencies. The vibrational
      spectra were interpreted with the aid of normal coordinate analysis. The results
      of the calculations were applied to simulated infrared and Raman spectra of the
      title compound which showed excellent agreement with the observed spectra.

PMID- 18715826
TI  - Can monitoring of intrathoracic impedance reduce morbidity and mortality in
      patients with chronic heart failure? Rationale and design of the Diagnostic
      Outcome Trial in Heart Failure (DOT-HF).
AB  - BACKGROUND: Chronic heart failure is associated with frequent hospitalisations
      which are often due to volume-overload decompensation. Monitoring of
      intrathoracic impedance, measured from an implanted device, can detect increases
      in pulmonary fluid retention early and facilitate timely treatment interventions.
      OBJECTIVE: The DOT-HF trial is designed to investigate if ambulatory monitoring
      of intrathoracic impedance together with other device-based diagnostic
      information can reduce morbidity and mortality in patients with chronic heart
      failure who are treated with cardiac resynchronization therapy (CRT) and/or an
      implantable defibrillator (ICD). METHODS: Approximately 2400 patients will be
      randomised in a 1:1 fashion to a management strategy with access to the
      diagnostic information from the implantable device ("access arm"), or a "control
      arm", where this information is not made available. Study subjects fulfil
      standard indications for CRT and/or ICD as outlined in current guidelines. In the
      access arm, a fluid alert algorithm is used to give early warning of decreasing
      intrathoracic impedance indicating a high risk of an impending volume-overload
      decompensation. The primary endpoint of DOT-HF is the composite of all-cause
      mortality or heart failure hospitalisation. Secondary and exploratory endpoints
      include all-cause mortality, the impact on total health care utilization, quality
      of life and cost effectiveness. The study is expected to close recruitment during
      2010 and to report in 2012.

PMID- 18715827
TI  - Timing of perialgal vacuole membrane differentiation from digestive vacuole
      membrane in infection of symbiotic algae Chlorella vulgaris of the ciliate
      Paramecium bursaria.
AB  - Each symbiotic Chlorella of the ciliate Paramecium bursaria is enclosed in a
      perialgal vacuole derived from the host digestive vacuole to protect from
      lysosomal fusion. To understand the timing of differentiation of the perialgal
      vacuole from the host digestive vacuole, algae-free P. bursaria cells were fed
      symbiotic C. vulgaris cells for 1.5min, washed, chased and fixed at various times
      after mixing. Acid phosphatase activity in the vacuoles enclosing the algae was
      detected by Gomori's staining. This activity appeared in 3-min-old vacuoles, and
      all algae-containing vacuoles demonstrated activity at 30min. Algal escape from
      these digestive vacuoles began at 30min by budding of the digestive vacuole
      membrane into the cytoplasm. In the budded membrane, each alga was surrounded by
      a Gomori's thin positive staining layer. The vacuoles containing a single algal
      cell moved quickly to and attached just beneath the host cell surface. Such
      vacuoles were Gomori's staining negative, indicating that the perialgal vacuole
      membrane differentiates soon after the algal escape from the host digestive
      vacuole. This is the first report demonstrating the timing of differentiation of
      the perialgal vacuole membrane during infection of P. bursaria with symbiotic
      Chlorella.

PMID- 18715828
TI  - ClyA cytolysin from Salmonella: distribution within the genus, regulation of
      expression by SlyA, and pore-forming characteristics.
AB  - Functional homologs of the Escherichia coli cytolysin A (clyA, hlyE, sheA) gene
      have recently been detected in Salmonella enterica serovars Typhi (S. Typhi) and
      Paratyphi A (S. Paratyphi A). In this study, analysis of a collection of
      Salmonella strains showed that all S. Typhi and S. Paratyphi A strains tested
      harbor an intact copy of the corresponding clyA variant, i.e. clyA(STy) and
      clyA(SPaA), respectively. On the other hand, clyA proved to be absent in the S.
      enterica serovar Paratyphi B and serovar Paratyphi C strains, in various non
      typhoid S. enterica subsp. enterica serovars (Typhimurium, Enteritidis,
      Choleraesuis, Dublin, and Gallinarum), and in S. enterica subsp. arizonae and
      Salmonella bongori strains. When grown under normal laboratory conditions, the S.
      Typhi and S. Paratyphi A strains produced only basal amounts of ClyA protein and
      did not exhibit a clyA-dependent hemolytic phenotype. RT-PCR and immunoblot
      analyses as well as phenotypic data revealed, however, that the expression of
      clyA(STy) and clyA(SPaA) can be activated by the Salmonella transcription factor
      SlyA. In addition, osmotic protection assays and lipid bilayer experiments
      demonstrated that the hemolytic ClyA(STy) and ClyA(SPaA) proteins are effective
      pore-forming toxins which, similar to E. coli ClyA, generate large, stable,
      moderately cation-selective channels in target membranes. Taken together with our
      recent serological findings which have indicated that S. Typhi and S. Paratyphi A
      strains produce substantial amounts of ClyA during human infection, these data
      suggest that ClyA may play a role in S. Typhi and S. Paratyphi A pathogenesis.

PMID- 18715829
TI  - What happens when Trypanosoma brucei leaves Africa.
AB  - Julius Lukes and co-workers evaluated the evolutionary origin of Trypanosoma
      equiperdum and Trypanosoma evansi, parasites that cause horse and camel diseases.
      Although similar to T. brucei, the sleeping-sickness parasite, these trypanosomes
      do not cycle through the tsetse fly and have been able to spread beyond Africa.
      Transmission occurs sexually, or via blood-sucking flies or vampire bats. They
      concluded that these parasites, which resemble yeast petite mutants, are T.
      brucei sub-species, which have evolved recently through changes in mitochondrial
      DNA.

PMID- 18715830
TI  - Fatigue in patients with chronic heart failure - a burden associated with
      emotional and symptom distress.
AB  - BACKGROUND: The relationship between experience of fatigue and emotional and
      symptom distress in chronic heart failure (CHF) needs to be thoroughly explored,
      because fatigue has major impact on daily activities in life. AIMS: The purpose
      was to examine the association between fatigue, as a multidimensional experience
      and anxiety, depression and symptom distress, and to explore the relationships
      between individual symptoms and the dimensions of fatigue in patients with CHF.
      METHODS: A consecutive sample of 112 patients with exacerbation of symptoms of
      CHF answered the Multidimensional Fatigue Inventory (MFI-20), the Hospital
      Depression and Anxiety (HAD) Scale and the Symptom Distress Scale (SDS). RESULTS:
      Anxiety was associated with mental fatigue, whereas depression was associated
      with reduction of activity, low motivation and decreased functioning. Physical
      fatigue was affected by symptom distress, with women reporting more distress than
      men. With exception of breathlessness, poor agreement was found between fatigue
      and the most intensive reported symptoms. CONCLUSIONS: The relationship between
      emotional distress and the experience of fatigue in patients with CHF may have a
      devastating affect on the patient's ability to cope and manage daily activities,
      including self-care and adherence to recommended treatment.

PMID- 18715831
TI  - An international/multicentre report on patients with cystic fibrosis (CF) over
      the age of 40 years.
AB  - BACKGROUND: The lifespan of patients with cystic fibrosis (CF) is increasing
      significantly. The objective of this international pilot study was to study the
      characteristics of these long-term survivors. METHODS: Four centres with large CF
      clinics from London (UK), Minneapolis (USA), Toronto (Canada) and Verona (Italy)
      identified 366 patients who had survived 40 years and longer. RESULTS: At all
      centres males survived longer than females. There were more pancreatic sufficient
      patients in Verona (60%) and Toronto (40%) than in London (16%) and Minneapolis
      (21%). The percentage of DeltaF508 homozygous patients varied between 47% in
      London and 45% in Minneapolis to only 26% in Toronto and 9% in Verona. Average
      FEV(1) and BMI values of the surviving population appeared to stabilise after 40
      years of age. FEV(1) was on average 12% higher in patients who were pancreatic
      sufficient (p > 0.0001). There was no difference in survival between the centres.
      The overall median survival after the age of 40 was 13 years. The estimated
      annual death rate was approximately 3.4% from the age of 40-60 years.
      CONCLUSIONS: Significant numbers of patients are now surviving to 40 years or
      more, and it is hoped that an in-depth study of these patients may identify the
      factors contributing to longer survival.

PMID- 18715832
TI  - Chiral separations in polar organic solvent chromatography: updating a screening
      strategy with new chlorine-containing polysaccharide-based selectors.
AB  - The screening conditions of an existing column and mobile phase selection
      strategy for chiral drug substances in polar organic solvent liquid
      chromatography (POSC) were tested for their applicability on two new chlorine
      containing polysaccharide-based stationary phases. The selectors of these phases
      are cellulose tris(3-chloro-4-methylphenylcarbamate) and amylose tris(5-chloro-2
      methylphenylcarbamate). The enantioselectivity of these phases is compared to
      that of the four phases (Chiralpak AD-RH, Chiralcel OD-RH, Chiralpak AS-RH and
      Chiralcel OJ-RH) used in the earlier defined strategy. A test set of 62
      structurally diverse chiral drug substances is analyzed using the screening
      conditions of the strategy on the six phases. The results confirm that the
      acetonitrile-based mobile phase provides a higher success rate and better
      resolutions than the methanol-based also on the new phases. However, the
      importance of the methanol-based mobile phase cannot be neglected for
      complementarity reasons; the two mobile phases insure enantioselectivity for
      different compounds. A third (ethanol-based) mobile phase, not part of the
      strategy, was also used to screen the two new phases. The joint results led to
      different possibilities to upgrade the current screening strategy so that
      improved success rates are obtained. The chlorine-containing chiral stationary
      phases demonstrated to have an added value to the screening process since they
      provided enantioresolution for compounds not resolved by non-chlorine-containing
      ones.

PMID- 18715833
TI  - "Can breast feeding help you in later life? Evidence from German military heights
      in the early 20th century".
AB  - Considerable literature exists on the benefits of breast feeding on the health
      and survival of infants and young children, but there is less on the effects on
      later life outcomes. One such measure of health and well-being that has received
      attention in the historical literature is terminal adult stature. Information on
      height is rather widely available; however, it is much more difficult to obtain
      data on breast feeding. One country that does have such information is Imperial
      Germany (1871-1919). A number of physicians and local health officials collected
      information on the incidence and duration of breast feeding early in the 20th
      century, particularly because of concern about the unusually high infant
      mortality rates in parts of Germany. Hallie Kintner has surveyed the published
      results of these studies. The information on the prevalence of breast feeding for
      the period 1903/10 has been inputed into a database of demographic and economic
      variables for the counties (Regierungsbezirke) of Germany (1850-1939). There are
      also published data on heights of military recruits from the Imperial German
      military forces in 1906. These can be linked to areas in the database and related
      to breast feeding practices and infant mortality both contemporaneously and
      approximately 20 years previous to 1906. Results indicate a significant effect of
      infant feeding practices on later life outcomes operating through infant health
      conditions, proxied by the infant mortality rate.

PMID- 18715834
TI  - Nondysgerminomatous ovarian tumors: clinical characteristics, treatment, and
      outcome. A case-controlled study.
AB  - OBJECTIVE: The aim of this study is to assess the response of patients with
      nondysgerminomatous ovarian germ-cell tumors (NDOGCT) to platinum-based
      chemotherapy and to determine association of prognostic factors to relapse of
      disease. METHODS: We retrospectively reviewed 21 patients who had surgical
      resection of nondysgerminomatous ovarian germ-cell tumors (NDOGCT) and received
      adjuvant chemotherapy in Vali-e-Asr Hospital, Tehran, Iran during 1997-2004. The
      median age at presentation was 18 years and the median follow-up was 20 months.
      Histological type of tumors included the following: immature teratoma (n=7),
      mixed germ-cell tumor (n=7), yolk sac tumors (n=4), and embryonal carcinoma
      (n=3). Distribution by stage at the time of surgery was as follows; stage I
      (n=10), stage III (n=6), and stage IV (n=5). RESULTS: Sixteen patients underwent
      unilateral salpingo-oophorectomy and 5 patients underwent cystectomy. After the
      initial surgery, 13 patients immediately received chemotherapy and the other 8
      patients received chemotherapy at a median time of 5.5 months (range, 1-40
      months). Postoperative chemotherapy included the following: bleomycin, etoposide,
      and cisplatin (n=17); vincristine, actinomycin-D, and cyclophosphamide (n=2);
      methotrexate, etoposide, and cisplatin (n=l); and cisplatin (n=l). Thirty-one
      percent of the patients suffered a relapse after platinum-based combination
      chemotherapy. The median disease-free survival was 40 months and the median
      overall survival was 50 months. The 5-year survival rate was 39%. CONCLUSIONS:
      This study showed that stage at the initial surgery, residual disease and the
      interval from initial diagnosis to the start of chemotherapy were possible
      prognostic factors for relapse. Also, our study indicates that there may be a
      role for aggressive cytoreductive surgery in advance NDOGCT, and a need for
      second-line combination chemotherapy.

PMID- 18715835
TI  - Changes in PDGF concentration in surgically treated colorectal carcinoma.
AB  - PURPOSE: The aim of the present study was to asses the effect of tumor
      advancement, differentiation grade and surgery treatment on PDGF- AB level and
      platelet (PLT) count depending on the site of blood collection. MATERIAL AND
      METHODS: The study included 38 patients submitted to surgical treatment due to
      diagnosis of colorectal cancer (CRC) without remote metastasis: G2- 20 patients
      and group G3- 18 patients. The control group consisted of 24 healthy subjects. In
      CRC patients the blood samples was collected three times: 1) before surgery, 2)
      intrasurgically and 3) 90 days after surgery. Serum PDGF- AB concentration was
      determined by ELISA- Kit reagents. RESULTS: PDGF concentration in all the
      patients was several times higher than in the control group, irrespective of
      tumor differentiation grade and the site of blood collection. However the level
      of PDGF- AB in intraoperatively collected arterial blood and venous blood in
      group G3 (arterial blood- 379.9+/-12.1 ng/ml; venous blood- 398.4+/-13.2 ng/ml)
      was significantly higher than in group G2 (arterial blood- 169.4+/-88.6 ng/ml;
      venous blood- 194.2+/-84.0 ng/ml). No significant differences were observed
      between venous and arterial blood. No correlation was found between the PLT count
      and PDGF- AB concentration. CONCLUSION: High blood PDGF- AB concentration in CRC
      patients but no significant positive correlation observed between the PLT count
      and PDGF-AB suggest its neoplastic origin beside PLT. Determination of this
      factor in blood serum may have an important implication in early diagnosis of
      CRC, which is the second most common malignant neoplasm with high recurrence
      rates.

PMID- 18715836
TI  - Length at birth and effect of prenatal and postnatal factors on early wheezing
      phenotypes. Krakow epidemiologic cohort study.
AB  - The main goal of the study was to assess the pattern of risk factors having an
      impact on the onset of early wheezing phenotypes in the birth cohort of 468 two
      year-olds. A secondary objective was to investigate a possible association
      between early persistent wheezing and infant's length at birth. Approximately one
      third of the children in the study sample experienced wheezing in the first two
      years of life, and in about two third of cases (67%), the symptom developed
      within the first year of life. The early wheezing was easily reversible and in
      about 70% of the affected infants, the symptom receded in the second year of
      life. The adjusted relative risk ratio (RRR) of persistent wheezing increased
      with maternal atopy (RRR = 3.13; 95% CI: 1.35-7.27), house dampness (RRR = 3.94;
      95% CI: 1.26-12.3), parity (RRR = 2.56; 95% CI: 1.51-4.32) and prenatal ETS
      exposure (RRR = 1.13; 95% CI: 1.05-1.22), but was inversely associated with the
      infant's length at birth (RRR = 0.87; 95% CI: 0.76-0.99). The data support the
      hypothesis that wheezing phenotypes in early childhood and possibly later in life
      may already be programmed in the prenatal and early postnatal period when the
      respiratory system is completing its growth and maturation.

PMID- 18715837
TI  - Effect of cement dust exposure on phagocytic function of polymorphonuclear
      neutrophils in cement mill workers.
AB  - OBJECTIVES: Exposure to cement dust can cause various occupational health
      problems due to its increasing incidence and long-term complications. However,
      the influence of cement dust on phagocytic function of polymorphonuclear
      neutrophils (PMNs), has not as yet been investigated. Therefore, the aim of the
      study was to measure the phagocytic activity of PMNs by assessing chemilumiscence
      (CL) response in cement mill workers and controls. MATERIAL AND METHODS: In this
      study, 50 volunteer males, aged 25-60 years, apparently healthy and nonsmoking,
      were randomly selected from among cement mill workers. These workers were further
      classified into subgroups based on exposure duration of less than 10, 10-20, and
      more than 20 years. The controls were 50 healthy, nonsmoking, males who matched
      the study group with respect to age, height, weight, and socioeconomic status.
      The phagocytic function of PMNs, stimulated with opsonized zymosan, was
      determined by measuring CL response. RESULTS: The findings show a significant
      decrease in phagocytic activity of PMNs [PMNs OPZ p < 0.005] in cement mill
      workers compared to controls. CONCLUSION: It is concluded that exposure to cement
      dust can impair the phagocytic function of PMNs which is reflected in decreased
      chemiluminescence response.

PMID- 18715838
TI  - CYP2E1 mRNA expression, genetic polymorphisms in peripheral blood lymphocytes and
      liver abnormalities in Chinese VCM-exposed workers.
AB  - OBJECTIVE: To study the relationship between expression of cytochrome P4502E1
      (CYP2E1) in human lymphocytes, variant CYP2E1 genotype, exposure to vinyl
      chloride monomer (VCM), and liver abnormalities in VCM-exposed workers. METHODS:
      A case-control study was performed on 90 male occupationally exposed workers and
      42 matched male nonexposed controls. Data were collected based on health
      surveillance, workplace investigation and questionnaire Survey. Total RNA and DNA
      were isolated from peripheral blood lymphocytes, and CYP2E1 mRNA expression was
      determined using RT-PCR, and the presence of CYP2E1 polymorphisms was identified
      based on PCR-RFLP. RESULTS: The mRNA expression of CYP2E1 in exposed workers
      (0.89+/-0.46) was significantly higher than in nonexposed controls (0.61+/-0.35)
      (P < 0.01). Logistic regression analysis demonstrated a statistically significant
      association between CYP2E1 mRNA expression levels and liver abnormalities in the
      VCM-exposed workers (OR = 3.66, P < 0.05). The genotype frequency for CYP2E1
      variants among VCM-exposed workers was not significantly different between
      workers with liver abnormalities and those without. CONCLUSIONS: Liver
      abnormalities in subjects exposed to VCM are positively associated with
      expression of peripheral blood lymphocyte mRNA, which is significantly increased
      in exposed workers compared to nonexposed controls. Therefore, CYP2E1 mRNA levels
      may be useful for health surveillance and protection of VCM-exposed workers.

PMID- 18715839
TI  - Comparison of the in vitro hemolytic effects produced by alkoxyacetic acids on
      human and rat erythrocytes.
AB  - OBJECTIVES: The alkoxyacetic acids (AAAs) are urinary metabolites of
      alkoxyethanol solvents. It is well documented that these chemicals can cause
      acute hemolytic anemia in humans and laboratory animals. There are scarce data on
      the relative hemolytic activity of these acids. Likewise, information is lacking
      on the relationship between their hemolytic activity and physicochemical
      properties. The aim of this study was to compare the hemolytic activity of five
      AAAs in red blood cells (RBCs) derived from donors' blood and male Wistar rats.
      Moreover, the possible relationship between lipophilic and hemolytic activity of
      AAAs was also investigated. MATERIALS AND METHODS: The RBCs washed in TRIS
      buffer, pH 7.4, were adjusted to a packed cell volume (PCV) of about 20% and
      incubated in a water bath at 37 degrees C for 0-3 h in the presence of different
      concentrations of AAAs. The hemolytic effects, in terms of the changes in RBCs,
      PCV, mean corpuscular volume (MCV) and free hemoglobin (HGBfree) in incubation
      medium, were evaluated. Based on the dose-response relationship for RBCs, PCV and
      MCV, the effective concentration values (EC50) and their 95% confidence intervals
      (95% CI) were calculated. The octanol-water partition coefficient (log P) and
      distribution coefficient (log D) of AAAs were computed using PALLAS software. The
      correlation between log P and log D values for AAAs at pH 7.4 and their EC50 was
      analyzed. RESULTS: Human RBCs were 1.9-3.1 times more resistant to the hemolytic
      activity of AAAs than rat erythrocytes. Also, the hemolytic activity of
      individual AAAs did not differ considerably; the maximum differences ranging from
      2.0 to 3.3. The EC50 values of AAAs highly correlated with their log P and log D
      values. CONCLUSIONS: The relatively small differences between the hemolytic
      effects of AAAs on rat and human erythrocytes may be associated with the strong
      acidity and relatively similar lipophilicity of these chemicals.

PMID- 18715840
TI  - Pulmonary irritation after inhalation exposure to benzalkonium chloride in rats.
AB  - BACKGROUND: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC)
      with a C8 to C18 chain length of alkyl groups. Since BAC exerts toxic effects on
      microorganisms, it has been used as an effective germicide and preservative,
      mostly in cosmetic industry and medicine. However, the toxic potential of BAC may
      be hazardous to humans, due to the common use of preparations containing BAC as a
      preservative. MATERIAL AND METHODS: To assess the possible toxic effects of BAC,
      two-stage experiments were performed on female Wistar rats. At first, LC50 after
      a single exposure to BAC aerosol was determined. Then, the animals were exposed
      to BAC aerosol at 30 mg/m3 for 6 h, and for 3 days (6 h/day). The controls were
      unexposed rats. Directly after BAC exposure and 18 h afterwards, BALF
      concentrations were measured of total protein, Clara cell protein, matrix
      metalloproteinase-9 (MMP-9), hyaluronic acid (HA), immunoglobulin E (IgE) and
      cytokines (TF-alpha, IL-6 and MIP-20), lactate dehydrogenase (LDH) and GSH-S
      transferase (GST). RESULTS: The LC50 value for exposed rats was ca. 53 mg BAC in
      m3 air for 4 h. All the rats survived single and repeated inhalation exposure to
      30 mg/m3 BAC. After single and repeated exposure, lung weight, total protein, HA
      and LDH activity in BALF of exposed rats were higher than in controls while CC16
      levels were decreased. A significantly higher BALF concentration of IL-6 and IgE
      was noted in animals exposed to single and repeated doses. BALF concentrations of
      MMP-9, TNF-alpha, and MIP-2 in exposed rats were similar to those in control
      animals. CONCLUSION: BAC may be classified to class I acute inhalation toxicity.
      It showed a strong inflammatory and irritant activity on the lungs after 6h
      inhalation and stimulated dynamic patterns of IL-6 and IgE production and protein
      infiltration from blood vessels to BALF. Continued exposure resulted in cellular
      destruction, a statistically significant increase in LDH activity and a
      continuous decrease in CC16 concentration in BALF.

PMID- 18715841
TI  - Asthma arising in flavoring-exposed food production workers.
AB  - OBJECTIVES: While working for a small family-owned popcorn popping company, all
      of the three non-smoking workers developed a respiratory disease. Because of the
      newly identified associations between the flavoring chemicals and bronchiolitis
      obliterans, the specifics of these cases and their exposures were investigated to
      add to the body of knowledge of flavoring-related lung disease. MATERIALS AND
      METHODS: We obtained data on work processes as well as full-shift personal and
      area air samples for diacetyl, acetoin, 2-nonanone, acetaldehyde, and total
      volatile organic compounds. Air samples were collected on thermal desorption
      tubes for analysis by gas chromatography mass spectrometry. We also reviewed
      medical records and conducted interview with the workers. RESULTS: Air samples
      representative of the exposures that exacerbated asthma symptoms in two workers
      contained many different aldehydes. The data from interview and medical records
      and the high resolution computed tomograms of the chest indicated the presence of
      occupational asthma in all the three workers and possible bronchiolitis
      obliterans in two of them. This case series emphasizes a need for exposure
      reduction and medical surveillance among workers exposed to flavoring chemicals,
      and provides evidence for an increased risk of occupational asthma, as well as
      bronchiolitis obliterans, in flavoring-exposed workers.

PMID- 18715842
TI  - Towards increased alcohol intervention activity in Swedish occupational health
      services.
AB  - OBJECTIVES: To investigate the extent to which Swedish occupational physicians
      and nurses discuss alcohol issues with their patients, their reasons for and
      against addressing these issues, their amount of education in handling risky
      drinking, and factors that they believe could facilitate increased alcohol
      intervention activity in OHS. METHODS: All Swedish physicians and nurses in OHS
      were surveyed with a postal questionnaire. The questionnaire was returned by 313
      physicians (response rate 54%) and 759 nurses (response rate 69%). RESULTS: As
      much as 70% of the physicians and 85% of the nurses reported that they
      "frequently" discussed alcohol problems with their patients. The majority of both
      physicians (81%) and nurses (69%) admitted participating in a maximum of a half
      day training in handling risky drinking. Among the physicians, the most common
      reason for asking patients about their alcohol consumption was the clinical
      relevance (57%). Seventy-three per cent of the nurses initiated discussions about
      alcohol on the basis of questionnaire responses. Both the physicians (72%) and
      nurses (90%) said that the knowledge about counselling techniques to use when
      alcohol-related symptoms are evident was the most important facilitator to
      increased intervention activity. CONCLUSIONS: OHS professionals usually discuss
      alcohol-related issues with their patients. Nonetheless, they are interested in
      gaining further education and knowledge in this respect. The study results
      indicate that OHS is an important setting for alcohol prevention.

PMID- 18715843
TI  - Comments on Prof. Jedrychowski's paper.

PMID- 18715844
TI  - Maximal frustration as an immunological principle.
AB  - A fundamental problem in immunology is that of understanding how the immune
      system selects promptly which cells to kill without harming the body. This
      problem poses an apparent paradox. Strong reactivity against pathogens seems
      incompatible with perfect tolerance towards self. We propose a different view on
      cellular reactivity to overcome this paradox: effector functions should be seen
      as the outcome of cellular decisions which can be in conflict with other cells'
      decisions. We argue that if cellular systems are frustrated, then extensive cross
      reactivity among the elements in the system can decrease the reactivity of the
      system as a whole and induce perfect tolerance. Using numerical and mathematical
      analyses, we discuss two simple models that perform optimal pathogenic detection
      with no autoimmunity if cells are maximally frustrated. This study strongly
      suggests that a principle of maximal frustration could be used to build
      artificial immune systems. It would be interesting to test this principle in the
      real adaptive immune system.

PMID- 18715845
TI  - Why do fiddler crabs build chimneys?
AB  - Chimneys are mud mounds built by fiddler crabs that encircle the entrance to
      their burrow. Their function in many species is unknown. In Uca capricornis,
      crabs of both sexes and all sizes build chimneys, but females do so
      disproportionately more often. There are no differences in the immediate physical
      or social environments between crabs with and without a chimney. Chimney owners
      spend less time feeding and more time underground than non-owners. We show
      experimentally that burrows with a chimney are less likely to be located by an
      intruder. It is possible that some crabs construct chimneys around their burrow
      to conceal the entrance and reduce the risk of losing it to an intruder.

PMID- 18715846
TI  - Morphoproteomic profile of mTOR, Ras/Raf kinase/ERK, and NF-kappaB pathways in
      human gastric adenocarcinoma.
AB  - Preclinical studies using human gastric adenocarcinoma (GAC) cell lines have
      shown that the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, can
      inhibit tumor growth and that the extracellular signal-regulated kinase (ERK) of
      the Ras/Raf kinase/ERK pathway is related to chemoresistance and apoptosis. We
      examined the state of activation of components of mTOR, Ras/Raf kinase/ERK, and
      nuclear factor (NF)-kappaB signal transduction pathways, as well as cell cycle
      protein analyte correlates in GAC cases. Formalin-fixed paraffin-embedded tissue
      microarray blocks containing samples from 210 cases of GAC were examined.
      Immunohistochemistry was utilized to detect the following antigens: S100P,
      upstream stimulator of ERK, and NF-kappaB pathways; phosphorylated (p)-mTOR (Ser
      2448), p-ERK-1/2 (Thr 202/Tyr 204), and one of their common down-stream
      effectors, p-p70S6K(Thr 389); p-NF-kappaBp65(Ser 536); and cell cycle associated
      proteins, Ki-67, and S phase kinase-associated protein (Skp)2. Immunoreactivity
      (0 to 4+) of protein expression and compartmentalization were assessed by bright
      field microscopy. The majority of cases showed positive (1+ to 4+)
      cytoplasmic/plasmalemmal p-mTOR (88%), and moderate-strong (2+ to 4+) nuclear p
      p70S6K (93%) and nuclear S100P (81%) expression. A subset of cases exhibited
      moderate-strong nuclear p-ERK-1/2 (15%) and p-NF-kappaBp65 (36%) expression. The
      majority of cases showed concomitant moderate-strong (2+ to 4+) nuclear Ki-67
      (71%) and Skp2 (68%). Nuclear expression levels of p-ERK-1/2 and p-NF-kappaBp65,
      of p-p70S6K and p-NF-kappaB, and of Ki-67 and Skp2, respectively, showed
      significant linear correlations in GAC (p <0.001). Additionally, there were
      statistically significant differences in the mean expression levels of p-ERK-1/2
      and p-NF-kappaBp65 in diffuse vs intestinal types of GAC, with higher levels of
      both in the diffuse type ( p = 0.001 and p <0.0001, respectively). In summary,
      morphoproteomic analysis reveals constitutive activation of mTOR and to some
      extent, Ras/Raf kinase and NF-kappaB pathways in GAC, as evidenced by increased
      cytoplasmic p-mTOR, nuclear translocation of p-p70S6K and p-ERK-1/2
      phosphorylated at putative sites of activation (Ser 2448, Thr 389, and Thr
      202/Tyr 204, respectively), as well as correlative expression of cell cycle
      analytes, Ki-67, and Skp2. These results suggest that a prospective study is
      warranted to evaluate the use of morphoproteomic profiling of individual patients
      with GAC in order to design combinatorial treatment strategies that target the
      mTOR, Ras/Raf kinase/ERK, and/or NF-kappaB pathways.

PMID- 18715847
TI  - Kidney injury molecule-1 expression identifies proximal tubular injury in urate
      nephropathy.
AB  - Urate nephropathy in children is uncommon, occurring mostly in those who have
      undergone chemotherapy or radiotherapy. The characteristic obstruction of distal
      nephron tubules by uric acid precipitates is considered key to the subsequent
      parenchymal injury. Whether proximal tubular injury plays a role in urate
      nephropathy remains unclear. We report one case of acute urate nephropathy and
      one case of chronic urate nephropathy in two pediatric patients. In their renal
      biopsies, we demonstrate upregulation of kidney injury molecule-1 (KIM-1), a
      specific injury marker, in proximal tubular cells. This finding implicates a role
      for proximal tubular injury in urate nephropathy.

PMID- 18715848
TI  - Mouse spleen tissue as a staining intensity reference for immunohistochemistry.
AB  - Immunohistochemistry (IHC) is widely used in diagnostic practice and research,
      but it is limited due to its subjective nature and weakness in reproducibility.
      For successful interpretation, IHC requires an internal reference system that
      controls for procedural variables and provides a staining intensity reference. We
      investigated the feasibility of using mouse spleen tissue as an intensity
      reference in conventional IHC. Formalin-fixed, paraffin-embedded mouse (BALB/c)
      spleen tissue was stained with variable procedural conditions including primary
      antibody (Ab) types, antigen retrieval methods, chromogen exposure times, and
      secondary Ab concentrations. Mouse spleen tissue showed identical staining
      intensity regardless of primary Ab types, even without primary Ab, and showed
      minimal differences according to retrieval methods. However, it showed various
      staining intensities according to chromogen exposure time and secondary Ab
      concentration. When mouse spleen was included in tissue microarrays and compared
      with the c-erbB2 IHC scoring system, splenic B cells showed weak membrane
      staining compatible with score 1+, whereas splenic plasma cells showed strong
      staining intensity compatible with score 3+. These results show that mouse spleen
      tissue can serve as a staining intensity reference for the interpretation of IHC.

PMID- 18715849
TI  - Influence of Nrf2 genotype on pulmonary NF-kappaB activity and inflammatory
      response after traumatic brain injury.
AB  - Inflammatory response plays an important role in the pathogenesis of acute lung
      injury (ALI) after traumatic brain injury (TBI). Nuclear factor erythroid 2
      related factor 2 (Nrf2) is a key transcription factor that plays a crucial role
      in cytoprotection against inflammation. The present study explored the influence
      of Nrf2 genotype on the production of cytokines and on activation of
      transcription factors in a murine TBI model. Wild-type Nrf2 (+/+) and Nrf2 (-/-)
      deficient mice were subjected to a moderately severe weight-drop impact
      acceleration head injury. Lung wet/dry weight ratio, tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), intercellular
      adhesion molecule-1 (ICAM-1), and nuclear factor kapp-aB (NF-kappaB) were
      investigated at 24 hr after TBI. Nrf2 (-/-) mice were shown to have a greater
      increase in the lung wet/dry weight ratio compared to their wild-type Nrf2 (+/+)
      counterparts after TBI. This exacerbation of lung injury in Nrf2 (-/-) mice was
      associated with increased levels of TNF-alpha, IL-1beta, IL-6, ICAM-1, and their
      mediator, NF-kappaB. The results suggest that Nrf2 plays an important protective
      role in attenuating the pulmonary inflammatory response and NF-kappaB activation
      after TBI.

PMID- 18715850
TI  - Non-anion gap acidosis in asthma: clinical and laboratory features and outcomes
      for hospitalized patients.
AB  - Metabolic acidosis secondary to lactic acidosis may occur in acute, severe asthma
      and its presence suggests that respiratory muscle fatigue and tissue hypoxia play
      a major part in the pathogenesis. Non-anion gap metabolic acidosis (NAG acidosis)
      has also been reported in acute asthma but its impact on the clinical outcome has
      not been evaluated. The objective of this study was to evaluate the prevalence of
      NAG acidosis, characterize the laboratory findings, and determine its impact on
      clinical outcomes. Acid-base and electrolyte status and clinical outcomes were
      examined over a 1-yr (2005 calendar yr) period in 109 adult patients (38 males,
      71 females; age range 21 to 91 yr) hospitalized for asthma exacerbation. The
      cohort was divided into 3 groups: I. No metabolic acidosis (n = 66), II. Anion
      gap (AG) acidosis (n = 11), and III. NAG acidosis (n = 32). For each of the
      groups, laboratory findings were consistent, demonstrating a tendency to
      hyperchloremia in the NAG acidosis group. One subject in the NAG acidosis group
      died. NAG acidosis was associated with a statistically significant (p = 0.028)
      risk of requirement for mechanical ventilation necessitating admission to the
      Medical Intensive Care Unit (MICU); the odds ratio for intubation for NAG
      acidosis compared to other groups was 3.92. No difference, however, was detected
      in overall length of stay (LOS) in hospital for patients with NAG acidosis vs the
      other groups. NAG metabolic acidosis in acute asthma may be more prevalent than
      expected and may be associated with more frequent need for mechanical ventilation
      and admission to an intensive care unit.

PMID- 18715851
TI  - Corrected 17-alpha-hydroxyprogesterone values adjusted by a scoring system for
      screening congenital adrenal hyperplasia in premature infants.
AB  - This study investigated the use of corrected 17-alpha-hydroxyprogesterone (17
      OHP) values to detect congenital adrenal hyperplasia (CAH) in newborn infants. 17
      OHP concentrations in blood spots from 913 neonates were measured using a
      neonatal screening test. A prematurity index was calculated using a scoring
      system based on gestational age and birth weight. Blood spot 17-OHP
      concentrations divided by the sum of prematurity scores were defined as the
      corrected 17-OHP values. Preterm infants (<30 wk) and low birth weight infants
      (<1.0 kg) showed 3.9- and 3.8-fold higher blood spot 17-OHP concentrations than
      normal full term infants. However, no significant differences were observed in
      the corrected 17-OHP values between the groups. Blood spot 17-OHP levels yielded
      significant correlations with the prematurity index (r = 0.42, p <0.05). Positive
      results for CAH were obtained in 9.5% (n = 53) and 2.0% (n = 11) of 556 premature
      infants by the cutoffs of blood spot 17-OHP (>15.0 ng/ml) and corrected 17-OHP
      values (>13.0 ng/ml), respectively. Of the 53 positive subjects, 39 (73.6%)
      converted to negative after 1 to 5 mo without treatment. In summary, blood spot
      17-OHP levels are influenced by the prematurity of newborns. Use of corrected 17
      OHP values provide limited but helpful information in screening for CAH by
      reducing the rate of false-positive results, especially in premature infants.

PMID- 18715852
TI  - Delta neutrophil index in automated immature granulocyte counts for assessing
      disease severity of patients with sepsis.
AB  - This study investigated the relationship between calculated immature granulocyte
      (IG) counts and the severity of sepsis. Coagulation parameters, fibrinolytic
      indices, bacterial isolation rates in blood cultures, and mortality were observed
      in 237 patients with suspected sepsis. The difference in leukocyte subfractions
      (delta neutrophil index; DN) identified by a cytochemical myeloperoxidase
      reaction and by a nuclear lobularity assay was determined with a blood cell
      analyzer (ADVIA 120, Siemens, Inc.). DN was strongly correlated with manual IG
      counts (r = 0.75, p <0.05). Patients with high DN (>40%) averaged 40% lower in
      platelet count, 26% prolongation of prothrombin time (PT), and 35% diminution of
      antithrombin III (AT III) activity, vs those with low DN (5-20%). Overt
      disseminated intravascular coagulation was more prevalent as the DN increased,
      and reached a peak in patients with DN >40%. DN values were closely associated
      with PT (r = 0.35, p <0.05), AT III activity (r = -0.36, p <0.05), and platelet
      count (r = -0.27, p <0.05). Positive blood culture rate averaged 3.5-fold higher
      in patients with DN >40% vs the subgroup with low DN of 5-10%. The mortality rate
      of patients with DN >40% markedly exceeded the mortality rate of patients with DN
      of 5-10% (79% vs 15%, p <0.05). Thus, DN has implications for the severity of
      sepsis and may be valuable to assess the prognosis of patients with suspected
      sepsis.

PMID- 18715853
TI  - Variables that affect platelet function analyzer-100 (PFA-100) closure times and
      establishment of reference intervals in Korean adults.
AB  - The PFA-100 is an in vitro system for measurement of platelet function in whole
      blood. To establish reference intervals in the Korean population, we investigated
      the relationships between PFA-100 closure times and gender, ABO blood group,
      citrate concentration, and time of blood collection in 120 well-characterized
      healthy Korean adults. Gender did not affect closure time values. Blood group O
      was associated with longer collagen/epinephrine (CEPI) and collagen/ADP (CADP)
      closure times than non-O groups (p <0.0001 for both). Closure times were shorter
      in samples obtained in the morning vs the afternoon. Regression analysis showed
      an association between CEPI and CADP closure times (p <0.0001), but there were no
      associations between PFA-100 results and WBC count, hemoglobin, hematocrit,
      platelet count, and platelet-associated parameters. The reference intervals for
      CEPI and CADP closure times of 3.2% citrated blood were 80-162 and 64-121 sec,
      respectively. The reference intervals for PFA-100 closure times in healthy Korean
      adults were similar to those in Western populations. Flow obstruction was
      observed in 31 of 480 (6.5%) measurements, but routine performance of duplicate
      measurements was otherwise unnecessary because of acceptable CV values. PFA-100
      closure time should be interpreted with consideration of the patient's clinical
      presentation and factors such as ABO blood group and diurnal variation.

PMID- 18715854
TI  - Comparison of culture screening protocols for methicillin-resistant
      Staphylococcus aureus (MRSA) using a chromogenic agar (MRSA-Select).
AB  - To compare the culture screening protocols for methicillin-resistant
      Staphylococcus aureus (MRSA), a total of 300 duplicate nasal swabs (233 initial
      cultures and 67 weekly follow-up cultures) were collected consecutively from 233
      patients in the Intensive Care Unit (ICU). One swab was plated directly on MRSA
      Select agar (D-MRSA-Select) and observed at 24 hr. The duplicate swab was
      incubated in tryptic soy broth (TSB) with 6.5% NaCl for 24 hr, and then
      subcultured on MRSA-Select (B-MRSA-Select), BAP (B-BAP), and mannitol salt agar
      with 4 mg/L oxacillin (B-MSA(OXA)), and observed at 24 hr. MRSA was detected in
      13.7% (32/233) of the initial and 22.4% (15/67) of the follow-up specimens. A
      patient was classified as MRSA-positive if any of the media grew colonies that
      were tested and confirmed to be MRSA. In the initial screening samples, the
      sensitivities of D-MRSA-Select, B-MRSA-Select, B-BAP, and B-MSA(OXA) were 78.1%,
      84.4%, 78.1%, and 65.6%, respectively, and the specificities were 100%, 98.0%,
      83.1%, and 93.5%, respectively. The sensitivities of all but the B-MRSA-Select
      protocol were significantly lower (p <0.05). In follow-up screening, the
      sensitivities of D-MRSA-Select, B-MRSA-Select, B-BAP, and B-MSA(OXA) were 66.7%,
      86.7%, 66.7%, and 53.3%, respectively, and the specificities were 100%, 98.1%,
      90.4%, and 90.4%, respectively. D-MRSA-Select protocol was considered useful in
      screening for MRSA because it was fast, highly specific, and showed sensitivity
      comparable to B-BAP. Salt-containing enrichment broth in conjunction with MRSA
      Select (B-MRSA-Select) provides a promising way to increase sensitivity in
      initial and follow-up screening for MRSA.

PMID- 18715855
TI  - Use of real time PCR for rapid detection of Del phenotype in Taiwan.
AB  - During routine serologic procedures, Rh D(el) blood is often not identified and
      subsequently labeled as RhD-negative. Recently, several reports have shown the
      ability of D(el) blood to induce anti-D in RhD-negative recipients. Among Korean,
      Japanese, and Chinese, almost all individuals with D(el) blood have a nucleotide
      change in the RHD gene of 1227G>A (RHDK407K). Thus, nucleotide 1227A at RHD exon
      9 can be used as a marker for the D(el) phenotype in Asians. Real-time PCR for
      single nucleotide polymorphisms has been useful in biallelic discrimination of
      genomic sequence. Use of this methodology to identify 1227A will facilitate
      identification of blood units with the D(el) blood type and thus prevent
      potential sensitization of the RhD-negative recipients. In this study, real-time
      PCR-melting curve analysis at nucleotide 1227 of RHD exon 9 was performed on 990
      leftover blood samples. PCR analysis identified 22 samples with the 1227G+A
      pattern, 965 samples with the 1227G pattern, and 3 with negative real-time
      results. The RHDEL allele frequency is 0.0116 (22/1980) among Taiwanese. These
      real-time PCR patterns were validated through DNA sequencing analyses of RHD exon
      9 on 22 samples with the 1227G+A pattern and on 50 randomly selected samples from
      1227G individuals. The real-time PCR test was then analyzed in 118 apparently RhD
      negative Taiwanese donors, including 38 D(el) and 80 true RhD-negative donors,
      for efficiency studies. All of the D(el) samples (38, 100%) were found to have
      the 1227A pattern. Among the 80 serologic true RhD-negative samples, 77 were
      negative for real-time PCR results [1227A(-) /1227G(-)], 2 had the 1227G pattern
      [1227A(-)/1227G(+)], and one had the 1227A pattern [1227A(+)/ 1227G(-)]. Results
      of the melting curve analysis of RHD 1227A for the detection of D(el) among
      apparent RhD-negative individuals in Taiwan had the following characteristics:
      100% sensitivity; 98.75% specificity, positive predictive value of 97.44%;
      negative predictive value of 100%; and an efficiency of 99.15%. Melting curve
      analysis using RHD 1227A for detection of D(el) phenotype can be efficiently
      applied in eastern Asian countries, since almost all the D(el) type in eastern
      Asians have the characteristic 1227A mutation.

PMID- 18715856
TI  - Systematic analysis of stutters to enhance the accuracy of chimerism testing.
AB  - Post-transplantation chimerism testing is important to monitor the engraftment of
      donor stem cells and for the diagnosis of relapse. Detecting the presence of
      donor/recipient-specific short tandem repeats (STRs) is a frequently used method
      for engraftment study. Unfortunately, the interpretation of the STR-based
      chimerism tests is often subject to interference by the presence of a stutter
      peak, which is one 4-base repeat unit smaller than an authentic allele. The aim
      of this study was to systematically analyze and resolve the effect of stutter
      peaks on the interpretation of STR-based chimerism tests. The AmpFlSTR
      Identifiler Amplification kit (Applied Biosystems)was used to amplify 15 STR loci
      using genomic DNA from 30 randomly selected, healthy donors. We found that the
      stutter peaks had locus-specific characteristics. The stutter percentage was
      defined as the percentage of the stutter peak area/main STR peak area. Based on
      mean values for the 30 DNA samples, the stutter percentage varied from locus to
      locus and ranged from 3.12% to 10.71% for 15 STR loci. The locus-specific stutter
      effect can be eliminated through appropriately adjusted equations. The usefulness
      of these equations in the prediction of relapse was confirmed by the 5%
      sensitivity test. Hence, this report offers a valuable scheme to enhance the
      accuracy of chimerism testing.

PMID- 18715857
TI  - Unusual warm autoimmune hemolytic anemia in non-alcoholic steatohepatitis.
AB  - Warm autoimmune hemolytic anemia (WAIHA), a rare disease (0.2-1 per 100,000
      population), ranges from an indolent form with mild hemolysis to a life
      threatening condition that necessitates transfusion of incompatible red cells.
      WAIHA can be either idiopathic or secondary to medications or to a
      lymphoproliferative disorder. We report a case of profound hemolytic anemia in a
      liver-transplant eligible patient who was diagnosed with cirrhosis secondary to
      non-alcoholic steatohepatitis (NASH). The patient initially was treated with red
      cell transfusion, iv immunoglobulin, and steroids. He developed acute renal
      failure that required dialysis. Subsequent management included plasmapheresis and
      rituximab therapy. The patient developed hepatorenal syndrome and died from
      progressive hepatic failure. To our knowledge, this is the first report of an
      association between NASH and WAIHA.

PMID- 18715858
TI  - Use of bivalirudin to prevent thrombosis following orthotopic liver
      transplantation in a patient with Budd-Chiari syndrome and a history of heparin
      induced thrombocytopenia.
AB  - Type II heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome
      that may arise in a time-dependent manner following heparin therapy, placing
      patients at significant risk for thromboembolic events. Therapy includes
      anticoagulation with a direct thrombin inhibitor and avoidance of heparin. We
      report a patient with Budd-Chiari syndrome and a history of heparin-induced
      thrombocytopenia who presented for orthotopic liver transplant and required
      postoperative anticoagulation with bivalirudin. During the post-transplant graft
      function improvement, we observed a significant dose-effect alteration manifested
      by an increased bivalirudin dose requirement as factor V activity increased. This
      observation is an important consideration in the attempt to maintain an optimal
      balance between effective anticoagulation and a reduced risk of postoperative
      bleeding.

PMID- 18715859
TI  - Promyelocytic blast crisis of chronic myeloid leukemia during imatinib treatment.
AB  - A 32-yr-old man with the chronic phase of chronic myeloid leukemia (CML-CP) was
      treated with imatinib mesylate for 6 mo. The real-time quantitative reverse
      transcription PCR ratio for BCR/ABL in blood mRNA (BCR/ABL RT-QPCR) decreased
      from an initial value of 0.0159 to a low value of 0.0012 after 3 mo, indicating
      complete hematologic response. During the next 3 mo, the patient progressed to a
      promyelocytic blast crisis, displaying leukemic cells containing both BCR/ABL and
      PML/RARalpha chimeric mRNAs. Complete remission was achieved by therapy with all
      trans retinoic acid (ATRA) and high-dose imatinib mesylate. Using retrospective
      PML/RARalpha RT-QPCR with a bone marrow specimen obtained at the initial
      diagnosis of CML-CP, we quantified the mRNA ratio as 0.000321, suggesting that
      the clonal evolution of PML/RARalpha translocation occurred early in the CML-CP.

PMID- 18715860
TI  - Papillary glioneuronal tumor: a case report and review of the literature.
AB  - We report a papillary glioneuronal tumor occurring in the right frontal lobe of a
      26-yr-old woman and we review the pertinent literature. Papillary glioneuronal
      tumor (PGNT) is a rare cerebral neoplasm, identified in approximately 37 cases to
      date. In 2007, the World Health Organization (WHO) classified the PGNT as a grade
      I neuronal-glial tumor because of its biphasic neurocytic and glial components
      and indolent clinical course. Patients commonly present with headaches or
      seizures, but may be asymptomatic with the mass discovered incidentally upon
      neuroimaging. Histology demonstrates a pseudopapillary architecture with a single
      or a pseudostratified layer of glial cells overlying hyalinized vasculature with
      interpapillary regions of neurocytic or ganglion cells. Peripheral eosinophilic
      granular bodies, Rosenthal fibers, hemosiderin, and areas of calcification are
      often noted. The PGNT displays moderate cellularity and is typically devoid of
      necrosis, microvascular proliferation, and mitoses. Its immunohistochemical
      profile includes glial fibrillary acidic protein (GFAP)-positive glial cells,
      synaptophysin-positive interpapillary neurocytes, and MIB-1 labeling in the range
      of 1-2%.

PMID- 18715861
TI  - Negative results of a rapid antibody test for HIV in a 16-month-old infant with
      AIDS.
AB  - In a 16-mo-old infant born to an HIV-infected mother, repeatedly negative results
      of a HIV rapid antibody test had been reported during the past 6 mo. The infant
      presented with several HIV-defining illnesses and HIV RT-PCR testing confirmed
      the presence of HIV infection. There are at least 2 possible explanations for the
      child's false-negative rapid HIV test results: First, his primary antibody
      production may have been suppressed by the presence of maternal IgG antibodies.
      Second, his mother was highly immunosuppressed, so that the low level of
      maternally derived IgG was only detected by HIV-EIA and Western blot. Our data
      suggest that the HIV rapid antibody test may not be sufficiently sensitive to
      detect HIV antibodies in infants aged <18 mo.

PMID- 18715862
TI  - Foundation of diagnostic cytology.

PMID- 18715864
TI  - Structural and biochemical characterization of the oxidoreductase NmDsbA3 from
      Neisseria meningitidis.
AB  - DsbA is an enzyme found in the periplasm of Gram-negative bacteria that catalyzes
      the formation of disulfide bonds in a diverse array of protein substrates, many
      of which are involved in bacterial pathogenesis. Although most bacteria possess
      only a single essential DsbA, Neisseria meningitidis is unusual in that it
      possesses three DsbAs, although the reason for this additional redundancy is
      unclear. Two of these N. meningitidis enzymes (NmDsbA1 and NmDsbA2) play an
      important role in meningococcal attachment to human epithelial cells, whereas
      NmDsbA3 is considered to have a narrow substrate repertoire. To begin to address
      the role of DsbAs in the pathogenesis of N. meningitidis, we have determined the
      structure of NmDsbA3 to 2.3-A resolution. Although the sequence identity between
      NmDsbA3 and other DsbAs is low, the NmDsbA3 structure adopted a DsbA-like fold.
      Consistent with this finding, we demonstrated that NmDsbA3 acts as a thiol
      disulfide oxidoreductase in vitro and is reoxidized by Escherichia coli DsbB
      (EcDsbB). However, pronounced differences in the structures between DsbA3 and
      EcDsbA, which are clustered around the active site of the enzyme, suggested a
      structural basis for the unusual substrate specificity that is observed for
      NmDsbA3.

PMID- 18715865
TI  - Insights into the catalytic mechanism of tyrosine phenol-lyase from X-ray
      structures of quinonoid intermediates.
AB  - Amino acid transformations catalyzed by a number of pyridoxal 5'-phosphate (PLP)
      dependent enzymes involve abstraction of the Calpha proton from an external
      aldimine formed between a substrate and the cofactor leading to the formation of
      a quinonoid intermediate. Despite the key role played by the quinonoid
      intermediates in the catalysis by PLP-dependent enzymes, limited accurate
      information is available about their structures. We trapped the quinonoid
      intermediates of Citrobacter freundii tyrosine phenol-lyase with L-alanine and L
      methionine in the crystalline state and determined their structures at 1.9- and
      1.95-A resolution, respectively, by cryo-crystallography. The data reveal a
      network of protein-PLP-substrate interactions that stabilize the planar geometry
      of the quinonoid intermediate. In both structures the protein subunits are found
      in two conformations, open and closed, uncovering the mechanism by which binding
      of the substrate and restructuring of the active site during its closure protect
      the quinonoid intermediate from the solvent and bring catalytically important
      residues into positions suitable for the abstraction of phenol during the beta
      elimination of L-tyrosine. In addition, the structural data indicate a mechanism
      for alanine racemization involving two bases, Lys-257 and a water molecule. These
      two bases are connected by a hydrogen bonding system allowing internal transfer
      of the Calpha proton.

PMID- 18715866
TI  - Differential dephosphorylation of the FcRgamma immunoreceptor tyrosine-based
      activation motif tyrosines with dissimilar potential for activating Syk.
AB  - The cell surface-expressed gamma chain of the high affinity receptor for IgE
      (FcepsilonRI) can be phosphorylated on two tyrosine residues of the
      immunoreceptor tyrosine-based activation motif (ITAM), leading to recruitment and
      activation of spleen tyrosine kinase (Syk), a kinase that is essential for mast
      cell signaling and allergic responses. However, it is not known whether
      preferential phosphorylation or dephosphorylation of the two individual FcRgamma
      tyrosines (the N-terminal Tyr47 and C-terminal Tyr58) could regulate Syk
      activation. Herein we report that phosphorylation of only Tyr58 was able to
      elicit Syk phosphorylation and a weak rise in intracellular calcium, suggesting
      that Tyr58 phosphorylation may be distinctively important for Syk activation. In
      vitro and in vivo studies revealed that both Tyr47 and Tyr58 could be similarly
      phosphorylated. However, mass spectrometric analysis of the phosphorylated
      FcepsilonRgamma from bone marrow-derived mast cells showed that phosphorylation
      at Tyr47 was at least 2-fold greater than at Tyr58. This suggested that, once
      phosphorylated, Tyr58 is preferentially dephosphorylated. In vitro studies
      demonstrated more efficient dephosphorylation of Tyr58 (by the receptor
      associated phosphatases SHP-1 and SHP-2) than of Tyr47. Analysis of Syk binding
      to wild type and mutant phosphorylated FcepsilonRI revealed that mutation at
      Tyr58 almost completely ablated Syk binding, whereas mutation at Tyr47 moderately
      reduced Syk binding. The findings argue for a novel regulatory mechanism, where
      dephosphorylation of phospho-Tyr58 is likely to promote the down-regulation of
      Syk activation and suppression of mast cell responses.

PMID- 18715867
TI  - Lysyl-tRNA synthetase is a target for mutant SOD1 toxicity in mitochondria.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease
      affecting the motor neurons. The majority of familial forms of ALS are caused by
      mutations in the Cu,Zn-superoxide dismutase (SOD1). In mutant SOD1 spinal cord
      motor neurons, mitochondria develop abnormal morphology, bioenergetic defects,
      and degeneration. However, the mechanisms of mitochondrial toxicity are still
      unclear. One possibility is that mutant SOD1 establishes aberrant interactions
      with nuclear-encoded mitochondrial proteins, which can interfere with their
      normal trafficking from the cytosol to mitochondria. Lysyl-tRNA synthetase
      (KARS), an enzyme required for protein translation that was shown to interact
      with mutant SOD1 in yeast, is a good candidate as a target for interaction with
      mutant SOD1 at the mitochondrion in mammals because of its dual cytosolic and
      mitochondrial localization. Here, we show that in mammalian cells mutant SOD1
      interacts preferentially with the mitochondrial form of KARS (mitoKARS). KARS
      SOD1 interactions occur also in the mitochondria of the nervous system in
      transgenic mice. In the presence of mutant SOD1, mitoKARS displays a high
      propensity to misfold and aggregate prior to its import into mitochondria,
      becoming a target for proteasome degradation. Impaired mitoKARS import correlates
      with decreased mitochondrial protein synthesis. Ultimately, the abnormal
      interactions between mutant SOD1 and mitoKARS result in mitochondrial
      morphological abnormalities and cell toxicity. mitoKARS is the first described
      member of a group of mitochondrial proteins whose interaction with mutant SOD1
      contributes to mitochondrial dysfunction in ALS.

PMID- 18715868
TI  - Impaired protein aggregate handling and clearance underlie the pathogenesis of
      p97/VCP-associated disease.
AB  - Mutations in p97/VCP cause the multisystem disease inclusion body myopathy, Paget
      disease of the bone and frontotemporal dementia (IBMPFD). p97/VCP is a member of
      the AAA+ (ATPase associated with a variety of activities) protein family and has
      been implicated in multiple cellular processes. One pathologic feature in IBMPFD
      is ubiquitinated inclusions, suggesting that mutations in p97/VCP may affect
      protein degradation. The present study shows that IBMPFD mutant expression
      increases ubiquitinated proteins and susceptibility to proteasome inhibition. Co
      expression of an aggregate prone protein such as expanded polyglutamine in IBMPFD
      mutant cells results in an increase in aggregated protein that localizes to small
      inclusions instead of a single perinuclear aggresome. These small inclusions fail
      to co-localize with autophagic machinery. IBMPFD mutants avidly bind to these
      small inclusions and may not allow them to traffic to an aggresome. This is
      rescued by HDAC6, a p97/VCP-binding protein that facilitates the autophagic
      degradation of protein aggregates. Expression of HDAC6 improves aggresome
      formation and protects IBMPFD mutant cells from polyglutamine-induced cell death.
      Our study emphasizes the importance of protein aggregate trafficking to inclusion
      bodies in degenerative diseases and the therapeutic benefit of inclusion body
      formation.

PMID- 18715869
TI  - The Cth2 ARE-binding protein recruits the Dhh1 helicase to promote the decay of
      succinate dehydrogenase SDH4 mRNA in response to iron deficiency.
AB  - Iron is an essential nutrient that participates as a redox co-factor in a broad
      range of cellular processes. In response to iron deficiency, the budding yeast
      Saccharomyces cerevisiae induces the expression of the Cth1 and Cth2 mRNA-binding
      proteins to promote a genome-wide remodeling of cellular metabolism that
      contributes to the optimal utilization of iron. Cth1 and Cth2 proteins bind to
      specific AU-rich elements within the 3'-untranslated region of many mRNAs
      encoding proteins involved in iron-dependent pathways, thereby promoting their
      degradation. Here, we show that the DEAD box Dhh1 helicase plays a crucial role
      in the mechanism of Cth2-mediated mRNA turnover. Yeast two-hybrid experiments
      indicate that Cth2 protein interacts in vivo with the carboxyl-terminal domain of
      Dhh1. We demonstrate that the degradation of succinate dehydrogenase SDH4 mRNA, a
      known target of Cth2 on iron-deficient conditions, depends on Dhh1. In addition,
      we localize the Cth2 protein to cytoplasmic processing bodies in strains
      defective in the 5' to 3' mRNA decay pathway. Finally, the degradation of trapped
      SDH4 mRNA intermediates by Cth2 supports the 5' to 3' directionality of mRNA
      turnover. Taken together, these results suggest that Cth2 protein recruits the
      Dhh1 helicase to ARE-containing mRNAs to promote mRNA decay.

PMID- 18715870
TI  - Joint requirement for Rac and ERK activities underlies the mid-G1 phase induction
      of cyclin D1 and S phase entry in both epithelial and mesenchymal cells.
AB  - Cyclin D1 gene induction is a key event in G1 phase progression. Our previous
      studies indicated that signaling to cyclin D1 is cell type-dependent because the
      timing of cyclin D1 gene expression in MCF10A mammary epithelial cells and
      mesenchymal cells such as fibroblasts and vascular smooth muscle cells is very
      different, with epithelial cells first expressing cyclin D1 in early rather than
      mid-G1 phase. In this report, we induced a mesenchymal phenotype in MCF10A cells
      by long-term exposure to TGF-beta and used the control and transitioned cells to
      examine cell type specificity of the signaling pathways that regulate cyclin D1
      gene expression. We show that early-G1 phase cyclin D1 gene expression in MCF10A
      cells is under the control of Rac, whereas mid-G1 phase cyclin D1 induction
      requires parallel signaling from Rac and ERK, both in the control and
      transitioned cells. This combined requirement for Rac and ERK signaling is
      associated with an increased requirement for intracellular tension, Rb
      phosphorylation, and S phase entry. A similar co-regulation of cyclin D1 mRNA by
      Rac and ERK is seen in primary mesenchymal cells. Overall, our results reveal two
      mechanistically distinct phases of Rac-dependent cyclin D1 expression and
      emphasize that the acquisition of Rac/ERK co-dependence is required for the mid
      G1 phase induction of cyclin D1 associated with S phase entry.

PMID- 18715871
TI  - PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein
      phosphatase 4.
AB  - Protein serine/threonine phosphatase 4 (PP4c) is an essential polypeptide
      involved in critical cellular processes such as microtubule growth and
      organization, DNA damage checkpoint recovery, apoptosis, and tumor necrosis
      factor alpha signaling. Like other phosphatases of the PP2A family, PP4c
      interacts with regulatory proteins, which specify substrate targeting and
      intracellular localization. The identification of these regulatory proteins is,
      therefore, key to fully understanding the function of this enzyme class. Here,
      using a sensitive affinity purification/mass spectrometry approach, we identify a
      novel, stable cytosolic PP4c interacting partner, KIAA1622, which we have renamed
      PP4R4. PP4R4 displays weak sequence homology with the A (scaffolding) subunit of
      the PP2A holoenzyme and specifically associates with PP4c (and not with the
      related PP2Ac or PP6c phosphatases). The PP4c.PP4R4 interaction is disrupted by
      mutations analogous to those abrogating the association of PP2Ac with PP2A A
      subunit. However, unlike the PP2A A subunit, which plays a scaffolding role,
      PP4R4 does not bridge PP4c with previously characterized PP4 regulatory subunits.
      PP4c.PP4R4 complexes exhibit phosphatase activity toward a fluorogenic substrate
      and gammaH2AX, but this activity is lower than that associated with the
      PP4c.PP4R2.PP4R3 complex, which itself is less active than the free PP4c
      catalytic subunit. Our data demonstrate that PP4R4 forms a novel cytosolic
      complex with PP4c, independent from the complexes containing PP4R1, PP4R2.PP4R3,
      and alpha4, and that the regulatory subunits of PP4c have evolved different modes
      of interaction with the catalytic subunit.

PMID- 18715872
TI  - The IsdC protein from Staphylococcus aureus uses a flexible binding pocket to
      capture heme.
AB  - Staphylococcus aureus scavenges heme-iron from host hemoproteins using iron
      regulated surface determinant (Isd) proteins. IsdC is the central conduit through
      which heme is passed across the cell wall and binds this molecule using a NEAr
      Transporter (NEAT) domain. NMR spectroscopy was used to determine the structure
      of IsdC in complex with a heme analog, zinc-substituted protoporphyrin IX
      (ZnPPIX). The backbone coordinates of the ensemble of conformers representing the
      structure exhibit a root mean square deviation to the mean structure of 0.53 +/-
      0.11 angstroms. IsdC partially buries protoporphyrin within a large hydrophobic
      pocket that is located at the end of its beta-barrel structure. The central metal
      ion of the analog adopts a pentacoordinate geometry in which a highly conserved
      tyrosine residue serves as a proximal ligand. Consistent with the structure and
      its role in heme transfer across the cell wall, we show that IsdC weakly binds
      heme (K(D) = 0.34 +/- 0.12 microm) and that ZnPPIX rapidly dissociates from the
      protein at a rate of 126 +/- 30 s(-1). NMR studies of the apo-form of IsdC reveal
      that a 3(10) helix within the binding pocket undergoes a flexible to rigid
      transition as heme is captured. This structural plasticity may increase the
      efficiency of heme transfer across the cell wall by facilitating protein-protein
      interactions between apoIsdC and upstream hemoproteins.

PMID- 18715873
TI  - Functional clustering of mutations in the dimer interface of the nucleotide
      binding folds of the sulfonylurea receptor.
AB  - ATP-sensitive K(+) (K(ATP)) channels modulate their activity as a function of
      inhibitory ATP and stimulatory Mg-nucleotides. They are constituted by two
      proteins: a pore-forming K(+) channel subunit (Kir6.1, Kir6.2) and a regulatory
      sulfonylurea receptor (SUR) subunit, an ATP-binding cassette (ABC) transporter
      that confers MgADP stimulation to the channel. Channel regulation by MgADP is
      dependent on nucleotide interaction with the cytoplasmic nucleotide binding folds
      (NBF1 and NBF2) of the SUR subunit. Crystal structures of bacterial ABC proteins
      indicate that NBFs form as dimers, suggesting that NBF1-NBF2 heterodimers may
      form in SUR and other eukaryotic ABC proteins. We have modeled SUR1 NBF1 and NBF2
      as a heterodimer, and tested the validity of the predicted dimer interface by
      systematic mutagenesis. Engineered cysteine mutations in this region have
      significant effects, both positive and negative, on MgADP stimulation of K(ATP)
      channels in excised patches and on macroscopic channel activity in intact cells.
      Additionally, the mutations cluster in the model structure according to their
      functional effect, such that patterns of alteration emerge. Of note, three gain
      of-function mutations, leading to MgADP hyperstimulation of the channel, are
      located in the D-loop region at the center of the predicted dimer interface.
      Overall, the data support the idea that SUR1 NBFs assemble as heterodimers and
      that this interaction is functionally critical.

PMID- 18715874
TI  - AMP-activated protein kinase contributes to UV- and H2O2-induced apoptosis in
      human skin keratinocytes.
AB  - AMP-activated protein kinase or AMPK is an evolutionarily conserved sensor of
      cellular energy status, activated by a variety of cellular stresses that deplete
      ATP. However, the possible involvement of AMPK in UV- and H(2)O(2)-induced
      oxidative stresses that lead to skin aging or skin cancer has not been fully
      studied. We demonstrated for the first time that UV and H(2)O(2) induce AMPK
      activation (Thr(172) phosphorylation) in cultured human skin keratinocytes. UV
      and H(2)O(2) also phosphorylate LKB1, an upstream signal of AMPK, in an epidermal
      growth factor receptor-dependent manner. Using compound C, a specific inhibitor
      of AMPK and AMPK-specific small interfering RNA knockdown as well as AMPK
      activator, we found that AMPK serves as a positive regulator for p38 and p53
      (Ser(15)) phosphorylation induced by UV radiation and H(2)O(2) treatment. We also
      observed that AMPK serves as a negative feedback signal against UV-induced mTOR
      (mammalian target of rapamycin) activation in a TSC2-dependent manner. Inhibiting
      mTOR and positively regulating p53 and p38 might contribute to the pro-apoptotic
      effect of AMPK on UV- or H(2)O(2)-treated cells. Furthermore, activation of AMPK
      also phosphorylates acetyl-CoA carboxylase or ACC, the pivotal enzyme of fatty
      acid synthesis, and PFK2, the key protein of glycolysis in UV-radiated cells.
      Collectively, we conclude that AMPK contributes to UV- and H(2)O(2)-induced
      apoptosis via multiple mechanisms in human skin keratinocytes and AMPK plays
      important roles in UV-induced signal transduction ultimately leading to skin
      photoaging and even skin cancer.

PMID- 18715875
TI  - High MMP-9 activity characterises pleural tuberculosis correlating with granuloma
      formation.
AB  - Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction.
      Matrix metalloproteinase (MMP)-1 and -9 are implicated in immunopathology of
      pulmonary and central nervous system TB. There are few data on MMP activity in TB
      pleurisy. The present study investigated MMP-1, -2 and -9 and their specific
      inhibitors (tissue inhibitor of metalloproteinase (TIMP)-1 and -2) in tuberculous
      effusions, and correlated these with clinical and histopathological features.
      Clinical data, routine blood tests, and pleural fluid/biopsy material were
      obtained from 89 patients presenting with pleural effusions in a TB-endemic area.
      MMP-1, -2 and -9 were measured by zymography or western blot, and TIMP-1 and -2
      by ELISA. Pleural biopsies were examined microscopically, cultured for acid
      alcohol fast bacilli and immunostained for MMP-9. Tuberculous pleural effusions
      contained the highest concentrations of MMP-9 compared with malignant effusions
      or heart failure transudates. MMP-9 concentrations were highest in effusions from
      patients with granulomatous biopsies: median (interquartile range) 108 (61-218)
      pg x mL(-1) versus 43 (12-83) pg x mL(-1) in those with nongranulomatous pleural
      biopsies. MMP-1 and -2 were not upregulated in tuberculous pleural fluid. The
      ratio of MMP-9:TIMP-1 was significantly higher in TB effusions. Tuberculous
      pleurisy is characterised by a specific pattern of matrix metalloproteinase-9
      upregulation, correlating with the presence of granulomas and suggesting a
      specific role for matrix metalloproteinase-9 in inflammatory responses in
      tuberculous pleural disease.

PMID- 18715876
TI  - Lung structure and function of infants with recurrent wheeze when asymptomatic.
AB  - Infants with recurrent wheeze have repeated episodes of airways obstruction;
      however, relatively little is known about the structure and function of their
      lungs when not symptomatic. The current authors evaluated whether infants with
      recurrent wheeze have smaller airway lumens or thickened airway walls, as well as
      decreased airway function. High-resolution computed tomography images 1 mm thick
      were obtained at three anatomic locations at an elevated lung volume and at
      functional residual capacity. Forced expiratory flows were also measured in
      subjects with recurrent wheeze. Airway lumen, wall areas and lung tissue density
      were not significantly different for recurrent wheeze (n = 17) and control (n =
      14) subjects; however, subjects with recurrent wheeze had lower forced expiratory
      flows than predicted. Similar findings were obtained when subjects were grouped
      by exposure to tobacco smoke. These findings indicate that infants with recurrent
      wheeze, as well as exposure to tobacco smoke, have lower airway function when not
      symptomatic. The lower forced expiratory flows may result from a degree of airway
      narrowing that could not be resolved with the methodology employed or from other
      mechanisms, such as more collapsible airways or decreased pulmonary elastic
      recoil.

PMID- 18715877
TI  - Pseudomonas aeruginosa transmission is infrequent in New Zealand cystic fibrosis
      clinics.
AB  - Pseudomonas aeruginosa is an important pathogen in cystic fibrosis (CF). Although
      most patients harbour unique P. aeruginosa isolates, some clinics report patients
      sharing common strains. The overall importance of person-to-person transmission
      in P. aeruginosa acquisition and whether routine patient segregation is necessary
      remains uncertain. The present authors therefore investigated the extent of P.
      aeruginosa transmission in New Zealand CF clinics. New Zealand's seven major CF
      centres were assessed, combining epidemiological data with computer-assisted SalI
      DNA fingerprinting of 496 isolates from 102 patients. One cluster of related
      isolates was significantly more prevalent in the largest clinic than expected by
      chance. The seven patients with isolates belonging to this cluster had more
      contact with each other than the remaining patients attending this centre. No
      other convincing evidence of transmission was found in any of the other smaller
      clinics. Three P. aeruginosa strains believed to be transmissible between
      patients in Australian and British CF clinics are present in New Zealand, but
      there was no definite evidence they had spread. Pseudomonas aeruginosa
      transmission is currently infrequent in New Zealand cystic fibrosis clinics. This
      situation could change rapidly and ongoing surveillance is required. The current
      results confirm that computer-assisted SalI DNA fingerprinting is ideally suited
      for such surveillance.

PMID- 18715878
TI  - Skeletal muscle weakness, exercise tolerance and physical activity in adults with
      cystic fibrosis.
AB  - The aim of the present study was to investigate the prevalence of muscle weakness
      and the importance of physical inactivity in cystic fibrosis (CF), and its
      relationship to exercise tolerance and muscle strength. Exercise tolerance,
      skeletal and respiratory muscle strength were studied in a group of 64 adults
      with CF (age 26+/-8 yrs, FEV(1 % predicted) 65+/-19) and in 20 age-matched
      controls. Physical activity (PA) was assessed in 20 patients and all controls.
      Quadriceps muscle weakness was present in 56% of the patients. Peak oxygen uptake
      and 6-min walking distance were below normal in 89 and 75% of patients,
      respectively. Respiratory muscle strength was normal. The differences remained
      after correcting for PA. Quadriceps force was correlated to the 6-min walking
      distance but not to peak oxygen uptake. "Mild" PA (>3 metabolic equivalents
      (METS)) and the number of steps overlapped with controls, but CF patients had
      less moderate PA (>4.8 METS). Moderate PA was related to peak oxygen uptake and
      quadriceps force. Skeletal muscle weakness and exercise intolerance are prevalent
      in cystic fibrosis. Physical inactivity is a factor significantly contributing to
      exercise tolerance and skeletal muscle force in adults with cystic fibrosis, but
      these impairments are in excess to that expected from physical inactivity only.

PMID- 18715879
TI  - Nuclear survivin in pN2 nonsmall cell lung cancer: prognostic and clinical
      implications.
AB  - Patients with N2 nonsmall cell lung cancer (N2-NSCLC) represent heterogeneous
      groups. Survivin is a member of the inhibitor of apoptosis family. If N2-NSCLC
      patients could be stratified, based on survivin expression and/or its relation to
      cell cycle proteins, into homogeneous subgroups, certain therapies could be
      selected for those patients. Survivin expression in 78 surgically resected
      primary pathological N2-NSCLC tumours was evaluated using immunohistochemistry.
      Relationships of survivin expression to overall survival, clinical features and
      expression of six cell cycle-related proteins (pRb, cyclin D1, p16(INK4A), p53,
      p21(Waf1) and Ki-67) were analysed. Nuclear survivin and the number of
      mediastinal lymph node (LN) stations were independent prognostic factors. The
      patient group with combined negative survivin/single mediastinal LN station were
      the most favourable prognostic group, and was related to the clinical nodal
      factor. Indeed, patients with negative survivin/low Ki-67 labelling indices had
      the best survival, especially in nonsquamous histopathology. The current authors
      conclude that nuclear survivin is strongly related to lymph node metastasis and
      proliferative potentials in pathological N2 nonsmall cell lung cancer patients.
      Pre-operative N2 nonsmall cell lung cancer patients with combined negative
      nuclear survivin and a single mediastinal lymph node station, or low
      proliferative indices, particularly in clinical N0-1 disease and nonsquamous
      histopathology, respectively, are expected to have a favourable post-operative
      prognosis and may be candidates for primary resection.

PMID- 18715880
TI  - Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic
      insights into leptin-regulated mammary tumor growth and progression.
AB  - Obesity is a recently established risk factor for breast cancer incidence and
      mortality. A characteristic of obesity is elevated circulating levels of
      adipocyte-derived hormone leptin. Evidence indicates that leptin plays an
      important role in mammary tumor formation; however, the mechanisms involved are
      poorly understood. Toward better defining the role of leptin in breast cancer, we
      describe the identification of leptin-regulated genes in hormone-responsive
      Michigan Cancer Foundation-7 (MCF-7) human breast cancer cells using a microarray
      system. More than 64 leptin-regulated genes were identified including those for
      growth factors, cell cycle regulators, extracellular matrix (ECM) proteins, and
      genes associated with metastasis. Cell cycle genes up-regulated by leptin include
      cyclins D and G, cyclin-dependent kinase 2, p21, p27, and p16. Leptin suppressed
      the expression of transforming growth factor-beta , a cell cycle suppressor.
      Determining the significance of this effect, treatment of MCF-7 cells with TGFB1
      abrogated leptin-stimulated proliferation. Leptin up-regulated the expression of
      connective tissue growth factor, villin 2, and basigin, factors that are
      associated with ECM and are known to impact tumor growth. Finally, leptin induced
      the expression of anti-apoptotic genes BCL2 and survivin, and reduced the
      expression of apoptotic genes. The effect of leptin on MCF-7 survival was
      evaluated via TUNEL assay and demonstrated a sixfold reduction in apoptosis in
      leptin-treated cells, compared with controls. These data suggest leptin promotes
      mammary tumor growth through multiple mechanisms, including regulating the cell
      cycle, apoptosis, and by modulating the extracellular environment. The
      identification of leptin-regulated genes begins to provide mechanistic links into
      the relationship between obesity and breast cancer incidence and morbidity.

PMID- 18715881
TI  - Interferon-gamma inhibits cellular proliferation and ACTH production in
      corticotroph tumor cells through a novel janus kinases-signal transducer and
      activator of transcription 1/nuclear factor-kappa B inhibitory signaling pathway.
AB  - Interferon-gamma (IFNG) is a cytokine that exerts potent antiproliferative and
      tumoricidal effects in a variety of cancers. Moreover, IFNG modulates normal
      pituitary hormone secretion, and was shown to inhibit the expression of the ACTH
      precursor POMC in murine ACTH-secreting AtT-2010/21/2008 tumor cells. We have
      studied the functional role of IFNG on pituitary tumor cells, focusing on the
      involvement of IFNG in the molecular events leading to the control of POMC
      transcriptional repression. Herein, it is shown that IFNG inhibits AtT-20 tumor
      cell proliferation without inducing apoptosis. Unexpectedly, an activated janus
      kinases-signal transducer and activator of transcription (JAK-STAT1) cascade is
      required for IFNG inhibitory action on POMC promoter activity. Factor-kappa B (NF
      kappaB) is necessary for the inhibitory action of IFNG on Pomc transcription,
      since loss of NF-kappaB activity with IkappaB super-repressor abolishes this
      effect. In addition, 1 and 2 IFNG receptor immunoreactivity was detected in human
      corticotropinoma cells. Interestingly, IFNG inhibits ACTH production from these
      cells in primary cell culture, without affecting basal ACTH biosynthesis in
      normal non-tumoral pituitary cells. In conclusion, our data show for the first
      time that POMC transcription can be negatively regulated by a JAK-STAT1 and NF
      kappaB-dependent pathway.

PMID- 18715882
TI  - CYP2A6 activity in a healthy Spanish population: effect of age, sex, smoking, and
      oral contraceptives.
AB  - This study was performed to assess the influence of age, sex, smoking, and
      contraceptive use on CYP2A6 activity. In the metabolism of caffeine, the
      conversion of 1,7 dimethylxanthine (17X) to 1,7 dimethiylurate (17U) is catalyzed
      primarily by CYP2A6. CYP2A6 phenotype was determined by the urinary ratio 17U:17X
      in the interval of 4-5 h after caffeine intake in 179 healthy white Spaniards
      (102 women and 76 men). There were 99 non-smokers and 80 smokers. Among women, 26
      were taking oral contraceptives. The age was the most important predictive factor
      of CYP2A6 activity (P < 0.001) with older subjects having higher activity. The
      influence of the gender was more modest (P = 0.07) with women exhibiting
      borderline increased values of the CYP2A6 marker than men. Tobacco smoking did
      not affect CYP2A6 activity. However, the CYP2A6 marker resulted to be strongly
      related to the use of oral contraceptives. The women users of oral contraceptives
      had higher values of CYP2A6 marker than both women not taking oral contraceptives
      and men (P < 0.001 in both comparisons). The results indicate that age, oral
      contraceptive use, and possibly gender should be controlled in epidemiological
      studies dealing with CYP2A6 activity and its relationship with xenobiotics
      exposure and genetic or pathological factor.

PMID- 18715883
TI  - Etiology and outcome of patients presenting for poisoning to the emergency
      department in Taiwan: a prospective study.
AB  - Poisoning is one of the most common reasons for visiting the emergency department
      in many countries, and the pattern varies from countries to countries and time to
      time. To compare the etiology and outcome of poisoning patients in different
      gender and age groups, we conducted a prospective study at the emergency
      departments of two medical centers in southern Taiwan between January 2001 and
      December 2002. All cases of poisoning, excluding patients diagnosed as cases of
      alcohol or food poisoning, were included, and relevant information was collected.
      There were 1512 cases of poisoning observed with a male to female ratio of 1:1.2
      (684/828). Overall, drugs (49.9%) were the main agents involved, and a suicidal
      attempt (66.1%) was the predominant etiology. A total of 63 fatalities (4.2%)
      were observed and pesticides, especially paraquat, resulted in most fatalities.
      Patients aged 19-30 years constituted the most cases, and significant differences
      in exposure agents, causes, and fatality rates were found among different age and
      gender groups. The results are compatible with the trend reported by other Asian
      countries. This study also shows important differences existing in poisoning
      patients of different age and gender groups. Therefore, different poisoning
      prevention strategies should be applied to different groups.

PMID- 18715884
TI  - Analysis of T-cell proliferation and cytokine secretion in the individuals
      exposed to arsenic.
AB  - Over six million people in nine districts of West Bengal, India are exposed to
      very high levels of arsenic primarily through their drinking water. More than
      300,000 people showed arsenic-induced skin lesions in these districts. This is
      regarded as the greatest arsenic calamity in the world. Chronic arsenicosis
      causes varied dermatological signs ranging from pigmentation changes,
      hyperkeratosis to non-melanocytic cancer of skin, and also malignancies in
      different internal organs. Higher incidences of opportunistic infections are
      found in the arsenic-exposed individuals, indicating that their immune systems
      may be impaired somehow. We have thus investigated the effect of arsenic on T
      cell proliferation and cytokine secretion in 20 individuals with arsenic-induced
      skin lesions and compared the results with 18 arsenic-unexposed individuals. A
      marked dose-dependent suppression of Concanavalin A (Con A) induced T-cell
      proliferation was observed in the arsenic-exposed individuals compared with the
      unexposed (P < 0.001) individuals. This correlated with a significant decrease in
      the levels of secreted cytokines by the T cells (TNF-alpha, IFN-gamma, IL2, IL10,
      IL5, and IL4) in the exposed individuals (P < 0.001). Thus it can be inferred
      that arsenic exposure can cause immunosuppression in humans.

PMID- 18715885
TI  - IL-1beta as a determinant in silica-induced cytokine responses in monocyte
      endothelial cell co-cultures.
AB  - Alveolar macrophages and endothelial cells are both involved in lung inflammation
      and remodeling of lung alveolar structures. In the present study, monocytes
      (precursors for macrophages) were exposed to crystalline silica and examined for
      pro- and anti-inflammatory cytokine responses in non-contact co-cultures with
      endothelial cells. The time courses for silica-induced release of tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-1beta, and IL-8 both from co-cultures and
      monocyte mono-cultures showed an early peak at 5-10 h, almost no response at 20
      h, and a strong increase at 43 h. At 43 h, co-cultures also showed strongly
      increased IL-6 levels. Steady-state levels of mRNA roughly exhibited the same
      pattern of early up-regulation and reduced levels at 20 h. Compared with monocyte
      mono-cultures, silica induced a strong release of IL-1beta, IL-6, and IL-8, but
      not of TNF-alpha, after 43 h in co-cultures, whereas at 5 and 10 h a significant
      difference was only observed for the silica-induced IL-8 response. An antagonist
      to the IL-1 receptor strongly reduced IL-6 and IL-8 levels, whereas antibodies to
      TNF-alpha increased the levels of IL-1beta and IL-8. Thus, IL-1beta is suggested
      to be an important triggering factor that determines the silica-induced release
      of several of the other cytokines in this co-culture system.

PMID- 18715886
TI  - Toxicity of repeated intravenous injection of gene therapeutics for X-CGD in
      mice.
AB  - We made gene therapeutics for X-chronic granulomatous disease (CGD) by
      transducing murine bone marrow-derived stem cells with MT-gp91 retrovirus and
      evaluated possible toxicity in mice as a prerequisite for human clinical trials.
      Male C57BL/6 mice were injected intravenously with gene therapeutics for X-CGD
      twice at an interval of two weeks at 5 x 10(7) cells/kg and sacrificed 2 weeks
      after the last administration. Significant changes noted in gene therapeutics for
      X-CGD-treated animals were an increase in white blood cell counts and a slight
      decrease in albumin/globulin ratio. The red pulp hyperplasia in the spleen
      accompanied with an increase in organ weight was considered to result from the
      accumulation of gene therapeutics for X-CGD, bone marrow-derived stem cells, in
      the spleen. No anti-gp91 antibody was detected in the sera collected from the
      animals treated with gene therapeutics for X-CGD. No integration of gp91 DNA from
      retroviral vector was detected in chromosomal DNA of gonads in animals dosed with
      the test substance, indicating no potential of genomic integration. In
      conclusion, the repeated dose of gene therapeutics for X-CGD exerted no toxicity.
      The splenic red pulp hyperplasia and the increase observed in white blood cell
      counts and in spleen weights were considered as pharmacological changes induced
      by the treatment.

PMID- 18715887
TI  - Ofloxacin-associated retinopathy in rabbits: role of oxidative stress.
AB  - Ofloxacin, a quinolone, is an extensively used, well-tolerated antibacterial
      agent but has been reported to induce photosensitivity at low incidences. In the
      present investigation, the possible role of oxidative stress in ofloxacin-induced
      retinopathy in rabbits was evaluated. It was observed that ofloxacin at a dose
      rate of 10 and 20 mg/rabbit, twice daily for 21 consecutive days, resulted in
      significant elevation in the extent of lipid peroxidation and depletion of the
      blood glutathione levels. Marked alterations were also observed in various
      parameters of the glutathione-redox cycle. There was significant increase in the
      enzymic activity of glutathione peroxidase and glutathione reductase, whereas a
      significant decrease was observed in the activities of superoxide dismutase,
      catalase, and glutathione-S-transferase enzymes. Histopathological studies
      revealed retinal damage especially in the pigmented cell layer. Degenerative
      changes in liver and kidneys were also observed. Liver showed focal areas of
      necrosis, dilation of sinusoids, and cellular infiltration, whereas in kidneys,
      there was glomerular and tubular degeneration, suggesting impaired renal
      functioning.

PMID- 18715888
TI  - Melittin-induced [Ca2+]i increases and subsequent death in canine renal tubular
      cells.
AB  - The effect of melittin on cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and
      viability is largely unknown. This study examined whether melittin alters Ca(2+)
      levels and causes Ca(2+)-dependent cell death in Madin-Darby canine kidney (MDCK)
      cells. [Ca(2+)](i) and cell death were measured using the fluorescent dyes fura-2
      and WST-1 respectively. Melittin at concentrations above 0.5 microM increased
      [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was reduced by
      75% by removing extracellular Ca(2+). The melittin-induced Ca(2+) influx was also
      implicated by melittin-caused Mn(2+) influx. After pretreatment with 1 microM
      thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor), melittin-induced
      Ca(2+) release was inhibited; and conversely, melittin pretreatment abolished
      thapsigargin-induced Ca(2+) release. At concentrations of 0.5-20 microM, melittin
      killed cells in a concentration-dependent manner. The cytotoxic effect of 0.5
      microM melittin was nearly completely reversed by prechelating cytosolic Ca(2+)
      with BAPTA. Melittin at 0.5-2 microM caused apoptosis as assessed by flow
      cytometry of propidium iodide staining. Collectively, in MDCK cells, melittin
      induced a [Ca(2+)](i) rise by causing Ca(2+) release from endoplasmic reticulum
      and Ca(2+) influx from extracellular space. Furthermore, melittin can cause
      Ca(2+)-dependent cytotoxicity in a concentration-dependent manner.

PMID- 18715889
TI  - Synergistic action of sodium selenite and N-acetylcysteine in acetaminophen
      induced liver damage.
AB  - Acetaminophen (AAP) is a commonly used analgesic and antipyretic drug; however,
      when used in high doses, it causes fulminant hepatic necrosis in both humans and
      experimental animals. In this study, we investigated whether selenium (Se) and N
      acetylcysteine (NAC), alone or in combination, are protective against AAP
      toxicity in mice. At the beginning of the experiment, blood samples were taken
      from 10 of 350 mice. Then, the remaining mice were randomly allocated into four
      groups, each consisting of 35 animals. The 1st group received a single
      administration of AAP by gavage at a dose of 600 mg/kg-bw, p.o. The 2nd group
      (AAP-Se) was treated with sodium selenite (0.5 mg Se/kg-bw, p.o.) one hour after
      ingestion of AAP. The 3rd group (AAP-NAC) ingested AAP, 1.5 h later followed by
      NAC (500 mg/kg-bw, p.o.). The 4th group (AAP-Se-NAC) was given sodium selenite
      and NAC, 1 and 1.5 h after administration of AAP, respectively. From each group,
      blood samples of seven mice for each time point were taken at 4, 8, 24, and 48 h
      after AAP toxicity. Serum alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), lactate dehydrogenase (LDH) levels were measured.
      Compared with AAP group, the levels of ALT were lower after AAP ingestion in AAP
      NAC, AAP-Se, and AAP-Se-NAC groups at the 8th hour. ALT, AST, and LDH levels in
      AAP-Se-NAC group were 50% of the levels of other groups starting form the 4th
      hour of toxicity. It is concluded that protection against AAP hepatotoxicity
      using a combination of Se and NAC is better than that found with either agent
      alone.

PMID- 18715890
TI  - Is beta-glucuronidase a clinical useful biomarker for an acute organophosphorus
      poisoning?
AB  - beta-glucuronidase is considered a sensitive biomarker for acute organophosphorus
      poisoning. In this well-documented study, multiple plasma samples over time were
      collected. A decrease in plasma concentration of beta-glucuronidase was
      surprisingly observed, even within normal range. These findings do not support
      the hypothesis that beta-glucuronidase is a useful biomarker for acute
      organophosphorus poisoning in humans.

PMID- 18715891
TI  - Myocardial lysis in a fetus induced by maternal paraphenylenediamine poisoning
      following an intentional ingestion to induce abortion.
AB  - The acute toxicity of paraphenylenediamine (PPD) has been associated with several
      histopathological changes. In humans, acute PPD poisoning is known to cause
      rhabdomyolisis and particularly myocardial lysis. However, its toxicity for the
      fetus has never been reported in the literature. We report a case of myocardial
      lysis in a fetus expelled by a 22-year-old mother after apparent ingestion of an
      unknown amount of PPD. The patient was admitted to our intensive care unit with
      acute onset of respiratory distress and rhabdomyolysis. The pelvic
      ultrasonography on admission showed a normally progressing pregnancy of 23-24
      weeks. On day 9 post-ingestion, the patient spontaneously expelled a non-viable
      fetus. The fetal examination did not show any external or macroscopic
      abnormalities. However, the histopathological exam showed an important heart and
      lung congestion. There was also some interstitial edema and inflammation at the
      base of the lingua, in addition to a chorionic villus thrombosis and abruptio
      placentae. The histopathology of the myocardium showed lysis of the cardiac
      muscle. This observation suggests that the PPD was most likely responsible for
      the myocardial injury in the fetus.

PMID- 18715892
TI  - Task-dependent modulation of propriospinal inputs to human shoulder.
AB  - In the human upper limb a proportion of the descending corticospinal command may
      be relayed through cervical propriospinal premotoneurons. This may serve to
      coordinate movements involving multiple joints of the arm, such as reaching. The
      present study was conducted to determine whether a shoulder stabilizing muscle,
      infraspinatus (INF), is functionally integrated into the putative cervical
      propriospinal network, and whether there is task-dependent modulation of the
      network. Fourteen healthy adults participated in this study. Responses in the
      right INF were evoked by transcranial magnetic stimulation over the motor cortex
      and compared with responses conditioned by ulnar nerve stimulation. Interstimulus
      intervals were chosen to summate inputs at the level of the premotoneurons.
      Participants performed a forearm and shoulder muscle cocontraction task or a grip
      lift task that also coactivated forearm and shoulder muscles. During the
      cocontraction task, INF motor-evoked potentials were significantly facilitated by
      ulnar nerve stimulation at low intensities and suppressed at higher intensities.
      Only facilitation reached significance during the grip-lift task. We have shown
      for the first time that propriospinal pathways may connect the hand to the
      rotator cuff of the shoulder. The modulation of facilitation/suppression during
      the grip-lift task suggests that inhibition of propriospinal premotoneurons is
      down-regulated in a task-dependent manner to increase the gain in the feedback
      reflex loop from forearm and hand muscles as required.

PMID- 18715893
TI  - Dendrite elongation and dendritic branching are affected separately by different
      forms of intrinsic motoneuron excitability.
AB  - Dendrites are the fundamental determinant of neuronal wiring. Consequently
      dendritic defects are associated with numerous neurological diseases and mental
      retardation. Neuronal activity can have profound effects on dendritic structure,
      but the mechanisms controlling distinct aspects of dendritic architecture are not
      fully understood. We use the Drosophila genetic model system to test the effects
      of altered intrinsic excitability on postembryonic dendritic architecture
      development. Targeted dominant negative knock-downs of potassium channel subunits
      allow for selectively increasing the intrinsic excitability of a selected subset
      of motoneurons, whereas targeted expression of a genetically modified
      noninactivating potassium channel decrease intrinsic excitability in vivo. Both
      manipulations cause significant dendritic overgrowth, but by different
      mechanisms. Increased excitability causes increased dendritic branch formation,
      whereas decreased excitability causes increased dendritic branch elongation.
      Therefore dendritic branching and branch elongation are controlled by separate
      mechanisms that can be addressed selectively in vivo by different manipulations
      of neuronal intrinsic excitability.

PMID- 18715894
TI  - Evidence for a role of connexin 43 in trigeminal pain using RNA interference in
      vivo.
AB  - The importance of glial cells in the generation and maintenance of neuropathic
      pain is becoming widely accepted. We examined the role of glial-specific gap
      junctions in nociception in the rat trigeminal ganglion in nerve-injured and 
      uninjured states. The connexin 43 (Cx43) gap-junction subunit was found to be
      confined to the satellite glial cells (SGCs) that tightly envelop primary sensory
      neurons in the trigeminal ganglion and we therefore used Cx43 RNA interference
      (RNAi) to alter gap-junction function in SGCs. Using behavioral evaluation,
      together with immunocytochemical and Western blot monitoring, we show that Cx43
      increased in the trigeminal ganglion in rats with a chronic constriction injury
      (CCI) of the infraorbital nerve. Reducing Cx43 expression using RNAi in CCI rats
      reduced painlike behavior, whereas in non-CCI rats, reducing Cx43 expression
      increased painlike behavior. The degree of painlike behavior in CCI rats and
      intact, Cx43-silenced rats was similar. Our results support previous suggestions
      that increases in glial gap junctions after nerve injury increases nociceptive
      behavior but paradoxically the reduction of gap junctions in normal ganglia also
      increases nociceptive behavior, possibly a reflection of the multiple functions
      performed by glia.

PMID- 18715895
TI  - Synaptic homeostasis in a zebrafish glial glycine transporter mutant.
AB  - Truncated escape responses characteristic of the zebrafish shocked mutant result
      from a defective glial glycine transporter (GlyT1). In homozygous GlyT1 mutants,
      irrigating brain ventricles with glycine-free solution rescues normal swimming.
      Conversely, elevating brain glycine levels restores motility defects. These
      experiments are consistent with previous studies that demonstrate regulation of
      global glycine levels in the CNS as a primary function of GlyT1. As GlyT1 mutants
      mature, their ability to mount an escape response naturally recovers. To
      understand the basis of this recovery, we assay synaptic transmission in primary
      spinal motor neurons by measuring stimulus-evoked postsynaptic potentials. At the
      peak of the motility defect, inhibitory synaptic potentials are both
      significantly larger and more prolonged indicating a prominent role for GlyT1 in
      shaping fast synaptic transmission. However, as GlyT1 mutants naturally regain
      their ability to swim, the amplitude of inhibitory potentials decreases to below
      wild-type levels. In parallel with diminishing synaptic potentials, the glycine
      concentration required to evoke the mutant motility defect increases 61-fold
      during behavioral recovery. Behavioral recovery is also mirrored by a reduction
      in the levels of both glycine receptor protein and transcript. These results
      suggest that increased CNS glycine tolerance and reduced glycine receptor
      expression in GlyT1 mutants reflect compensatory mechanisms for functional
      recovery from excess nervous system inhibition.

PMID- 18715896
TI  - Different roles of related currents in fast and slow spiking of model neurons
      from two phyla.
AB  - Neuronal activity arises from the interplay of membrane and synaptic currents.
      Although many channel proteins conducting these currents are phylogenetically
      conserved, channels of the same type in different animals can have different
      voltage dependencies and dynamics. What does this mean for our ability to derive
      rules about the role of different types of ion channels in neuronal activity? Can
      results about the role of a particular channel type in a particular type of
      neuron be generalized to other neuron types? We compare spiking model neurons in
      two databases constructed by exploring the maximal conductance spaces of two
      models. The first is a model of crustacean stomatogastric neurons, and the second
      is a model of rodent thalamocortical neurons, but both models contain similar
      types of membrane currents. Spiking neurons in both databases show distinct fast
      and slow subpopulations, but our analysis reveals that related currents play
      different roles in fast and slow spiking in the stomatogastric versus
      thalamocortical neurons. This analysis involved conductance-space visualization
      and comparison of voltage traces, current traces, and frequency-current
      relationships from all spiker subpopulations. Our results are consistent with
      previous work indicating that the role a membrane current plays in shaping a
      neuron's behavior depends on the voltage dependence and dynamics of that current
      and may be different in different neuron types depending on the properties of
      other currents it is interacting with. Conclusions about the function of a type
      of membrane current based on experiments or simulations in one type of neuron may
      therefore not generalize to other neuron types.

PMID- 18715897
TI  - A dopamine-acetylcholine cascade: simulating learned and lesion-induced behavior
      of striatal cholinergic interneurons.
AB  - The giant cholinergic interneurons of the striatum are tonically active neurons
      (TANs) that respond with pauses to appetitive and aversive cues and to novel
      events. Whereas tonic activity emerges from intrinsic properties of these
      neurons, glutamatergic inputs from intralaminar thalamic nuclei and dopaminergic
      inputs from midbrain are required for genesis of pause responses. No prior
      computational models encompass both intrinsic and synaptically gated dynamics. We
      present a mathematical model that robustly accounts for behavior-related
      electrophysiological properties of TANs in terms of their intrinsic physiological
      properties and known afferents. In the model, balanced intrinsic hyperpolarizing
      and depolarizing currents engender tonic firing and glutamatergic inputs from
      thalamus (and cortex) both directly excite and indirectly inhibit TANs. If this
      inhibition, probably mediated by GABAergic nitric oxide synthase interneurons,
      exceeds a threshold, a persistent K+ conductance current amplifies its effect to
      generate a prolonged pause. Dopamine (DA) signals modulate both the intrinsic
      mechanisms and the external inputs of TANs. Simulations revealed that many
      learning-dependent behaviors of TANs, including acquired pauses to task-relevant
      cues, are explicable without recourse to learning-dependent changes in synapses
      onto TANs, due to a tight coupling between DA bursts and TAN pauses. These
      interactions imply that reward-predicting cues often cause striatal projection
      neurons to receive a cascade of signals: an adaptively scaled DA burst, a brief
      acetylcholine (ACh) burst, and an ACh pause. A sensitivity analysis revealed a
      unique TAN response surface, which shows that DA inputs robustly cooperate with
      thalamic inputs to control cue-dependent pauses of ACh release, which strongly
      affects performance- and learning-related dynamics in the striatum.

PMID- 18715898
TI  - Physiological basis of limb-impedance modulation during free and constrained
      movements.
AB  - Arm stiffness is a critical factor underlying stable interactions with the
      environment. When the hand moves freely through space, a stiff limb would most
      effectively maintain the hand on the desired path in the face of external
      perturbations. Conversely, when constrained by a rigid surface, a compliant limb
      would allow the surface to guide the hand while minimizing variations in contact
      forces. We aimed to identify the physiological basis of stiffness adaptation for
      these two classes of movement. Stiffness can be regulated by two mechanisms:
      coactivation of antagonistic muscles and modulation of reflex gains. We
      hypothesized that subjects would select high stiffness (high coactivation and/or
      reflex gains) in free space and high compliance (low coactivation and reflex
      gains) for constrained movements. We measured EMG and the H-reflex during
      constrained and unconstrained movement of the wrist. As predicted, subjects
      coactivated antagonist muscles more when performing the unconstrained movement.
      Contrary to our hypothesis, however, H-reflex amplitude was higher for the
      constrained movement despite the a priori preference for lower reflex gains in
      this situation. In addition, the H-reflex depended on the task and the net force
      exerted by the limb on the environment, rather than showing a simple dependence
      on the level of muscle activation. Thus stiffness seems to increase in free space
      compared with constrained motion through the use of coactivation, whereas spinal
      loop gains are adjusted to better regulate the influence of afferences on the
      ongoing movement. These observations support the hypothesis of movement
      programming in terms of impedance.

PMID- 18715899
TI  - Molecular substrates mediating lanthanide-evoked neurotransmitter release in
      central synapses.
AB  - Noncanonical secretagogues such as hypertonicity or alpha-latrotoxin have been
      extremely informative in studying neurotransmission. Lanthanum and lanthanides
      can also trigger neurotransmitter release through an unknown mechanism. Here, we
      studied the effect of lanthanides on neurotransmission in hippocampal cultures.
      Application of 2 mM La3+ caused rapid and robust neurotransmitter release within
      seconds. In addition, transient application of La3+ uncovered a sustained
      facilitation of miniature neurotransmission. The response to La3+ was detectable
      at 2 microM and increased in a concentration-dependent manner<or=2 mM. Rapid
      effect of La3+ was independent of extracellular and intracellular Ca2+ and did
      not require La3+ entry into cells or activation of phospholipaseCbeta. Synapses
      deficient in synaptobrevin-2, the major synaptic vesicle soluble N-ethylmaleimide
      sensitive factor attachment protein receptor (SNARE) protein in the brain, did
      not display any rapid release in response to La3+, whereas the slow facilitation
      of release detected after La3+ removal remained intact. In contrast,
      preincubation with intracellular Ca2+ chelators selectively attenuated the
      delayed release triggered by La3+. Moreover, synapses deficient in synaptotagmin
      1 maintained a rapid response to La3+, suggesting that La3+-triggered
      neurotransmitter release does not require synaptotagmin-1 as a sensor. Therefore
      La3+ has two separate effects on synaptic transmission. For its rapid action,
      La3+ interacts with a target on the surface membrane, and unlike other forms of
      release, it triggers strictly synaptobrevin-2-dependent fusion, implying that in
      central synapses synaptobrevin-2 function is secretagogue specific. For the
      delayed action, La3+ may act intracellularly after its entry or through
      intracellular Ca2+ via a mechanism that does not require synaptobrevin-2.

PMID- 18715900
TI  - Coupling of L-type Ca2+ channels to KV7/KCNQ channels creates a novel, activity
      dependent, homeostatic intrinsic plasticity.
AB  - Experience-dependent modification in the electrical properties of central neurons
      is a form of intrinsic plasticity that occurs during development and has been
      observed following behavioral learning. We report a novel form of intrinsic
      plasticity in hippocampal CA1 pyramidal neurons mediated by the KV7/KCNQ and
      CaV1/L-type Ca2+ channels. Enhancing Ca2+ influx with a conditioning spike train
      (30 Hz, 3 s) potentiated the KV7/KCNQ channel function and led to a long-lasting,
      activity-dependent increase in spike frequency adaptation-a gradual reduction in
      the firing frequency in response to sustained excitation. These effects were
      abolished by specific blockers for CaV1/L-type Ca2+ channels, KV7/KCNQ channels,
      and protein kinase A (PKA). Considering the widespread expression of these two
      channel types, the influence of Ca2+ influx and subsequent activation of PKA on
      KV7/KCNQ channels may represent a generalized principle in fine tuning the output
      of central neurons that promotes stability in firing-an example of homeostatic
      regulation of intrinsic membrane excitability.

PMID- 18715905
TI  - Identification of direct transcriptional targets of the Kaposi's sarcoma
      associated herpesvirus Rta lytic switch protein by conditional nuclear
      localization.
AB  - Lytic reactivation from latency is critical for the pathogenesis of Kaposi's
      sarcoma-associated herpesvirus (KSHV). We previously demonstrated that the 691
      amino-acid (aa) KSHV Rta transcriptional transactivator is necessary and
      sufficient to reactivate the virus from latency. Viral lytic cycle genes,
      including those expressing additional transactivators and putative oncogenes, are
      induced in a cascade fashion following Rta expression. In this study, we sought
      to define Rta's direct targets during reactivation by generating a conditionally
      nuclear variant of Rta. Wild-type Rta protein is constitutively localized to cell
      nuclei and contains two putative nuclear localization signals (NLSs). Only one
      NLS (NLS2; aa 516 to 530) was required for the nuclear localization of Rta, and
      it relocalized enhanced green fluorescent protein exclusively to cell nuclei. The
      results of analyses of Rta NLS mutants demonstrated that proper nuclear
      localization of Rta was required for transactivation and the stimulation of viral
      reactivation. RTA with NLS1 and NLS2 deleted was fused to the hormone-binding
      domain of the murine estrogen receptor to generate an Rta variant whose nuclear
      localization and ability to transactivate and induce reactivation were tightly
      controlled posttranslationally by the synthetic hormone tamoxifen. We used this
      strategy in KSHV-infected cells treated with protein synthesis inhibitors to
      identify direct transcriptional targets of Rta. Rta activated only eight KSHV
      genes in the absence of de novo protein synthesis. These direct transcriptional
      targets of Rta were transactivated to different levels and included the genes nut
      1/PAN, ORF57/Mta, ORF56/Primase, K2/viral interleukin-6 (vIL-6), ORF37/SOX,
      K14/vOX, K9/vIRF1, and ORF52. Our data suggest that the induction of most of the
      KSHV lytic cycle genes requires additional protein expression after the
      expression of Rta.

PMID- 18715906
TI  - Toll-like receptor 3 has a protective role against West Nile virus infection.
AB  - Protection against West Nile virus (WNV) infection requires rapid viral sensing
      and the generation of an interferon (IFN) response. Mice lacking IFN regulatory
      factor 3 (IRF-3) show increased vulnerability to WNV infection with enhanced
      viral replication and blunted IFN-stimulated gene (ISG) responses. IRF-3
      functions downstream of several viral sensors, including Toll-like receptor 3
      (TLR3), RIG-I, and MDA5. Cell culture studies suggest that host recognizes WNV in
      part, through the cytoplasmic helicase RIG-I and to a lesser extent, MDA5, both
      of which activate ISG expression through IRF-3. However, the role of TLR3 in vivo
      in recognizing viral RNA and activating antiviral defense pathways has remained
      controversial. We show here that an absence of TLR3 enhances WNV mortality in
      mice and increases viral burden in the brain. Compared to congenic wild-type
      controls, TLR3(-/-) mice showed relatively modest changes in peripheral viral
      loads. Consistent with this, little difference in multistep viral growth kinetics
      or IFN-alpha/beta induction was observed between wild-type and TLR3(-/-)
      fibroblasts, macrophages, and dendritic cells. In contrast, a deficiency of TLR3
      was associated with enhanced viral replication in primary cortical neuron
      cultures and greater WNV infection in central nervous system neurons after
      intracranial inoculation. Taken together, our data suggest that TLR3 serves a
      protective role against WNV in part, by restricting replication in neurons.

PMID- 18715907
TI  - Natural killer cells as novel helpers in anti-herpes simplex virus immune
      response.
AB  - Innate defenses help to eliminate infection, but some of them also play a major
      role in shaping the magnitude and efficacy of the adaptive immune response. With
      regard to influencing subsequent adaptive immunity, NK cells aided by dendritic
      cells may be the most relevant components of the innate reaction to herpes
      simplex virus (HSV) infection. We confirm that mice lacking or depleted of NK
      cells are susceptible to HSV-induced lesions. The quantity and quality of CD8(+)
      cytotoxic T lymphocytes generated in the absence of NK cells were diminished,
      thereby contributing to susceptibility to HSV-induced encephalitis. We
      demonstrate a novel helper role for NK cells, in that NK cells compensate for the
      loss of CD4 helper T cells and NK cell supplementation enhances the function of
      wild type anti-HSV CD8 T cells. In addition, NK cells were able to partially
      rescue the dysfunctional CD8(+) T cells generated in the absence of CD4 T helper
      cells, thereby performing a novel rescue function. Hence, NK cells may well be
      exploited for enhancing and rescuing the T-cell response in situations where the
      CD4 helper response is affected.

PMID- 18715908
TI  - Nef can enhance the infectivity of receptor-pseudotyped human immunodeficiency
      virus type 1 particles.
AB  - Nef is an accessory protein of human immunodeficiency virus type 1 (HIV-1) that
      enhances the infectivity of progeny virions when expressed in virus-producing
      cells. The requirement for Nef for optimal infectivity is, at least in part,
      determined by the envelope (Env) glycoprotein, because it can be eliminated by
      pseudotyping HIV-1 particles with pH-dependent Env proteins. To investigate the
      role of Env in the function of Nef, we have examined the effect of Nef on the
      infectivity of Env-deficient HIV-1 particles pseudotyped with viral receptors for
      cells expressing cognate Env proteins. We found that Nef significantly enhances
      the infectivity of CD4-chemokine receptor pseudotypes for cells expressing HIV-1
      Env. Nef also increased the infectivity of HIV-1 particles pseudotyped with Tva,
      the receptor for subgroup A Rous sarcoma virus (RSV-A), even though Nef had no
      effect if the pH-dependent Env protein of RSV-A was used for pseudotyping.
      However, Nef does not always enhance viral infectivity if the normal orientation
      of the Env-receptor interaction is reversed, because the entry of Env-deficient
      HIV-1 into cells expressing the vesicular stomatitis virus G protein was
      unaffected by Nef. Together, our results demonstrate that the presence of a viral
      Env protein during virus production is not required for the ability of Nef to
      increase viral infectivity. Furthermore, since the infectivity of Tva pseudotypes
      was blocked by inhibitors of endosomal acidification, we conclude that low-pH
      dependent entry does not always bypass the requirement for Nef.

PMID- 18715909
TI  - Identification of a broad-spectrum arenavirus entry inhibitor.
AB  - Several arenaviruses, including Lassa virus (LASV), are causative agents of
      hemorrhagic fever, for which effective therapeutic options are lacking. The LASV
      envelope glycoprotein (GP) gene was used to generate lentiviral pseudotypes to
      identify small-molecule inhibitors of viral entry. A benzimidazole derivative
      with potent antiviral activity was identified from a high-throughput screen
      utilizing this strategy. Subsequent lead optimization for antiviral activity
      identified a modified structure, ST-193, with a 50% inhibitory concentration
      (IC(50)) of 1.6 nM against LASV pseudotypes. ST-193 inhibited pseudotypes
      generated with other arenavirus envelopes as well, including the remaining four
      commonly associated with hemorrhagic fever (IC(50)s for Junin, Machupo,
      Guanarito, and Sabia were in the 0.2 to 12 nM range) but exhibited no antiviral
      activity against pseudotypes incorporating either the GP from the LASV-related
      arenavirus lymphocytic choriomeningitis virus (LCMV) or the unrelated G protein
      from vesicular stomatitis virus, at concentrations of up to 10 microM.
      Determinants of ST-193 sensitivity were mapped through a combination of LASV-LCMV
      domain-swapping experiments, genetic selection of viral variants, and site
      directed mutagenesis. Taken together, these studies demonstrate that sensitivity
      to ST-193 is dictated by a segment of about 30 amino acids within the GP2
      subunit. This region includes the carboxy-terminal region of the ectodomain and
      the predicted transmembrane domain of the envelope protein, revealing a novel
      antiviral target within the arenavirus envelope GP.

PMID- 18715910
TI  - Herpes simplex virus type 1 ICP0 phosphorylation mutants impair the E3 ubiquitin
      ligase activity of ICP0 in a cell type-dependent manner.
AB  - Herpes simplex virus type 1 (HSV-1) infected cell protein 0 (ICP0) is a 110-kDa
      nuclear phosphoprotein that is required for both the efficient initiation of
      lytic infection and the reactivation of quiescent viral genomes from latency. The
      ability of ICP0 to act as a potent viral transactivator is mediated by its N
      terminal zinc-binding RING finger domain. This domain confers E3 ubiquitin ligase
      activity to ICP0 and is required for the proteasome-dependent degradation of a
      number of cellular proteins during infection, including the major nuclear domain
      10 (ND10) constituent protein promyelocytic leukemia. In previous work we mapped
      three phosphorylation regions within ICP0, two of which directly affected its
      transactivation capabilities in transient transfection assays (Davido et al., J.
      Virol. 79:1232-1243, 2005). Because ICP0 is a phosphoprotein, we initially sought
      to test the hypothesis that phosphorylation regulates the E3 ubiquitin ligase
      activity of ICP0. Although none of the mutations affected ICP0 E3 ligase activity
      in vitro, transient transfection analysis indicated that mutations within one or
      more of the phosphorylated regions impaired the ability of ICP0 to form foci with
      colocalizing conjugated ubiquitin and to disrupt ND10. Mutations within one of
      the regions also affected ICP0 stability, and all of these phenomena occurred in
      a cell type-dependent manner. In the context of viral infection, only one ICP0
      phosphorylation mutant (P1) showed a significant defect in viral replication and
      enhanced protein stability compared to all the other viruses tested. This study
      suggests that specific cellular environments and context of expression
      (transfection versus infection) differentially regulate several activities of
      ICP0 related to its E3 ubiquitin ligase activity via phosphorylation.

PMID- 18715911
TI  - Insertion of an EYFP-pp71 (UL82) coding sequence into the human cytomegalovirus
      genome results in a recombinant virus with enhanced viral growth.
AB  - The human cytomegalovirus (HCMV) UL82-encoded tegument protein pp71 has recently
      been shown to activate viral immediate-early (IE) gene expression by neutralizing
      a cellular intrinsic immune defense instituted by the ND10 protein hDaxx. Pp71
      localizes to ND10 upon infection and induces the degradation of hDaxx. Here, we
      report the successful generation of a recombinant HCMV expressing enhanced yellow
      fluorescent protein (EYFP) fused to the N terminus of pp71. Intriguingly,
      insertion of the EYFP-UL82 coding sequence into the HCMV AD169 genome gave rise
      to a recombinant virus, termed AD169/EYFP-pp71, that replicates to significantly
      higher titers than wild-type AD169. In particular, we noticed strongly increased
      protein levels of pp71 after AD169/EYFP-pp71 inoculation. Although the high
      abundance of pp71 resulted in augmented packaging of the tegument protein into
      viral particles, no increased hDaxx degradation was detectable upon AD169/EYFP
      pp71 infection. In contrast, further investigation revealed a significantly
      enhanced viral DNA replication compared to wild-type AD169. Thus, we hypothesize
      that an as-yet-unidentified function of pp71 contributes to the enhanced
      infectivity of AD169/EYFP-pp71. This assumption is additionally supported by the
      observation that increased early and late gene expression after AD169/EYFP-pp71
      infection occurs independent of elevated IE protein levels. Finally,
      immunofluorescence analyses confirmed that hDaxx determines the ND10-localization
      of pp71 upon infection, since pp71 exhibited a nucleolar distribution in the
      absence of hDaxx. Taken together, we generated a recombinant HCMV that
      constitutes a useful tool not only to dissect the in vivo dynamics of pp71
      subnuclear localization more precisely but also to explore new features of this
      viral transactivator.

PMID- 18715912
TI  - Characterization of a CRM1-dependent nuclear export signal in the C terminus of
      herpes simplex virus type 1 tegument protein UL47.
AB  - The herpes simplex virus type 1 tegument protein known as VP13/14, or hUL47,
      localizes to the nucleus and binds RNA. Using fluorescence loss in photobleaching
      analysis, we show that hUL47 undergoes nucleocytoplasmic shuttling during
      infection. We identify the hUL47 nuclear export signal (NES) as a C-terminal 10
      residue hydrophobic peptide and measure its efficiency relative to that of the
      classical human immunodeficiency virus type 1 Rev NES. Finally, we show that the
      hUL47 NES is sensitive to the inhibitor of CRM1-mediated nuclear export
      leptomycin B. Hence, hUL47 joins a growing list of virus-encoded RNA-binding
      proteins that use CRM1 to exit the nucleus.

PMID- 18715913
TI  - A dynamic view of hepatitis C virus replication complexes.
AB  - Hepatitis C virus (HCV) replicates its genome in a membrane-associated
      replication complex (RC). Specific membrane alterations, designated membranous
      webs, represent predominant sites of HCV RNA replication. The principles
      governing HCV RC and membranous web formation are poorly understood. Here, we
      used replicons harboring a green fluorescent protein (GFP) insertion in
      nonstructural protein 5A (NS5A) to study HCV RCs in live cells. Two distinct
      patterns of NS5A-GFP were observed. (i) Large structures, representing membranous
      webs, showed restricted motility, were stable over many hours, were partitioned
      among daughter cells during cell division, and displayed a static internal
      architecture without detectable exchange of NS5A-GFP. (ii) In contrast, small
      structures, presumably representing small RCs, showed fast, saltatory movements
      over long distances. Both populations were associated with endoplasmic reticulum
      (ER) tubules, but only small RCs showed ER-independent, microtubule (MT)
      dependent transport. We suggest that this MT-dependent transport sustains two
      distinct RC populations, which are both required during the HCV life cycle.

PMID- 18715914
TI  - The C terminus of foamy retrovirus Gag contains determinants for encapsidation of
      Pol protein into virions.
AB  - Foamy viruses (FV) differ from orthoretroviruses in many aspects of their
      replication cycle. A major difference is in the mode of Pol expression,
      regulation, and encapsidation into virions. Orthoretroviruses synthesize Pol as a
      Gag-Pol fusion protein so that Pol is encapsidated into virus particles through
      Gag assembly domains. However, as FV express Pol independently of Gag from a
      spliced mRNA, packaging occurs through a distinct mechanism. FV genomic RNA
      contains cis-acting sequences that are required for Pol packaging, suggesting
      that Pol binds to RNA for its encapsidation. However, it is not known whether Gag
      is directly involved in Pol packaging. Previously our laboratory showed that
      sequences flanking the three glycine-arginine-rich (GR) boxes at the C terminus
      of FV Gag contain domains important for RNA packaging and Pol expression,
      cleavage, and packaging. We have now shown that both deletion and substitution
      mutations in the first GR box (GR1) prevented neither the assembly of particles
      with wild-type density nor packaging of RNA genomes but led to a defect in Pol
      packaging. Site-directed mutagenesis of GR1 indicated that the clustered
      positively charged amino acids in GR1 play important roles in Pol packaging. Our
      results suggest that GR1 contains a Pol interaction domain and that a Gag-Pol
      complex is formed and binds to RNA for incorporation into virions.

PMID- 18715915
TI  - Three-dimensional organization of Rift Valley fever virus revealed by
      cryoelectron tomography.
AB  - Rift Valley fever virus (RVFV) is a member of the Bunyaviridae virus family
      (genus Phlebovirus) and is considered to be one of the most important pathogens
      in Africa, causing viral zoonoses in livestock and humans. Here, we report the
      characterization of the three-dimensional structural organization of RVFV vaccine
      strain MP-12 by cryoelectron tomography. Vitrified-hydrated virions were found to
      be spherical, with an average diameter of 100 nm. The virus glycoproteins formed
      cylindrical hollow spikes that clustered into distinct capsomeres. In contrast to
      previous assertions that RVFV is pleomorphic, the structure of RVFV MP-12 was
      found to be highly ordered. The three-dimensional map was resolved to a
      resolution of 6.1 nm, and capsomeres were observed to be arranged on the virus
      surface in an icosahedral lattice with clear T=12 quasisymmetry. All icosahedral
      symmetry axes were visible in self-rotation functions calculated using the
      Fourier transform of the RVFV MP-12 tomogram. To the best of our knowledge, a
      triangulation number of 12 had previously been reported only for Uukuniemi virus,
      a bunyavirus also within the Phlebovirus genus. The results presented in this
      study demonstrate that RVFV MP-12 possesses T=12 icosahedral symmetry and suggest
      that other members of the Phlebovirus genus, as well as of the Bunyaviridae
      family, may adopt icosahedral symmetry. Knowledge of the virus architecture may
      provide a structural template to develop vaccines and diagnostics, since no
      effective anti-RVFV treatments are available for human use.

PMID- 18715916
TI  - Accelerated prion disease pathogenesis in Toll-like receptor 4 signaling-mutant
      mice.
AB  - Prion diseases such as scrapie involve the accumulation of disease-specific prion
      protein, PrP(Sc), in the brain. Toll-like receptors (TLRs) are a family of
      proteins that recognize microbial constituents and are central players in host
      innate immune responses. The TLR9 agonist unmethylated CpG DNA was shown to
      prolong the scrapie incubation period in mice, suggesting that innate immune
      activation interferes with prion disease progression. Thus, it was predicted that
      ablation of TLR signaling would result in accelerated pathogenesis. C3H/HeJ
      (Tlr4(Lps-d)) mice, which possess a mutation in the TLR4 intracellular domain
      preventing TLR4 signaling, and strain-matched wild-type control (C3H/HeOuJ) mice
      were infected intracerebrally or intraperitoneally with various doses of scrapie
      inoculum. Incubation periods were significantly shortened in C3H/HeJ compared
      with C3H/HeOuJ mice, regardless of the route of infection or dose administered.
      At the clinical phase of disease, brain PrP(Sc) levels in the two strains of mice
      showed no significant differences by Western blotting. In addition, compared with
      macrophages from C3H/HeOuJ mice, those from C3H/HeJ mice were unresponsive to
      fibrillogenic PrP peptides (PrP residues 106 to 126 [PrP(106-126)] and PrP(118
      135)) and the TLR4 agonist lipopolysaccharide but not to the TLR2 agonist
      zymosan, as measured by cytokine production. These data confirm that innate
      immune activation via TLR signaling interferes with scrapie infection.
      Furthermore, the results also suggest that the scrapie pathogen, or a
      component(s) thereof, is capable of stimulating an innate immune response that is
      active in the central nervous system, since C3H/HeJ mice, which lack the
      response, exhibit shortened incubation periods following both intraperitoneal and
      intracerebral infections.

PMID- 18715917
TI  - Genetically divergent strains of feline immunodeficiency virus from the domestic
      cat (Felis catus) and the African lion (Panthera leo) share usage of CD134 and
      CXCR4 as entry receptors.
AB  - The env open reading frames of African lion (Panthera leo) lentivirus (feline
      immunodeficiency virus [FIV(Ple)]) subtypes B and E from geographically distinct
      regions of Africa suggest two distinct ancestries, with FIV(Ple)-E sharing a
      common ancestor with the domestic cat (Felis catus) lentivirus (FIV(Fca)). Here
      we demonstrate that FIV(Ple)-E and FIV(Fca) share the use of CD134 (OX40) and
      CXCR4 as a primary receptor and coreceptor, respectively, and that both lion
      CD134 and CXCR4 are functional receptors for FIV(Ple)-E. The shared usage of
      CD134 and CXCR4 by FIV(Fca) and FIV(Ple)-E may have implications for in vivo cell
      tropism and the pathogenicity of the E subtype among free-ranging lion
      populations.

PMID- 18715918
TI  - Analysis of the interaction between the UL11 and UL16 tegument proteins of herpes
      simplex virus.
AB  - The UL11 and UL16 tegument proteins of herpes simplex virus are conserved
      throughout the herpesvirus family. Previous studies have shown that these
      proteins interact, perhaps to link UL16-bound nucleocapsids to UL11, which
      resides on the cytoplasmic face of the trans-Golgi network, where maturation
      budding occurs. Little is known about the interaction except that it requires the
      leucine-isoleucine (LI) and acidic cluster motifs in UL11 and that no other viral
      proteins are involved. In particular, the important question of whether these two
      proteins bind to each other directly has not been addressed. Accordingly, UL11
      and UL16 were expressed in bacteria, and the purified proteins were found to
      retain the ability to interact in a manner that was dependent upon the LI and
      acidic cluster. In an attempt to map the UL11-binding site contained in UL16, a
      large number of deletion mutants were constructed. The first 40 (nonconserved)
      amino acids were found to be dispensable, but all the other constructs failed to
      bind UL11 or had poor expression in transfected cells, suggesting that UL16 is
      very sensitive to alterations and probably lacks a multidomain structure. As an
      alternative strategy for identifying residues that are important for the
      interaction, the cysteines of UL16 were investigated, because many of these are
      highly conserved. Approximately half of the 20 cysteines in UL16 have been shown
      to be covalently modified by N-ethylmaleimide, and this treatment was found to
      block the interaction with UL11. Moreover, individual serine replacements of six
      of the most conserved cysteine residues were made, and four of these disrupted
      the interaction with UL11 without affecting protein stability. However, the UL11
      UL16 interaction does not involve the formation of interspecies disulfide bonds,
      because binding occurred even when all the cysteines in UL11 were eliminated.
      Thus, UL16 directly interacts with UL11 and does so in a manner that requires
      free cysteines.

PMID- 18715919
TI  - Enhancement of human immunodeficiency virus (HIV)-specific CD8+ T cells in
      cerebrospinal fluid compared to those in blood among antiretroviral therapy-naive
      HIV-positive subjects.
AB  - During untreated human immunodeficiency virus type 1 (HIV-1) infection, virus
      specific CD8(+) T cells partially control HIV replication in peripheral lymphoid
      tissues, but host mechanisms of HIV control in the central nervous system (CNS)
      are incompletely understood. We characterized HIV-specific CD8(+) T cells in
      cerebrospinal fluid (CSF) and peripheral blood among seven HIV-positive
      antiretroviral therapy-naive subjects. All had grossly normal brain magnetic
      resonance imaging and spectroscopy and normal neuropsychometric testing.
      Frequencies of epitope-specific CD8(+) T cells by direct tetramer staining were
      on average 2.4-fold higher in CSF than in blood (P = 0.0004), while HIV RNA
      concentrations were lower. Cells from CSF were readily expanded ex vivo and
      responded to a broader range of HIV-specific human leukocyte antigen class I
      restricted optimal peptides than did expanded cells from blood. HIV-specific
      CD8(+) T cells, in contrast to total CD8(+) T cells, in CSF and blood were at
      comparable maturation states, as assessed by CD45RO and CCR7 staining. The strong
      relationship between higher T-cell frequencies and lower levels of viral antigen
      in CSF could be the result of increased migration to and/or preferential
      expansion of HIV-specific T cells within the CNS. This suggests an important role
      for HIV-specific CD8(+) T cells in control of intrathecal viral replication.

PMID- 18715920
TI  - Resistance mutations in human immunodeficiency virus type 1 integrase selected
      with elvitegravir confer reduced susceptibility to a wide range of integrase
      inhibitors.
AB  - Integration of viral DNA into the host chromosome is an essential step in the
      life cycle of retroviruses and is facilitated by the viral integrase enzyme. The
      first generation of integrase inhibitors recently approved or currently in late
      stage clinical trials shows great promise for the treatment of human
      immunodeficiency virus (HIV) infection, but virus is expected to develop
      resistance to these drugs. Therefore, we used a novel resistance selection
      protocol to follow the emergence of resistant HIV in the presence of the
      integrase inhibitor elvitegravir (GS-9137). We find the primary resistance
      conferring mutations to be Q148R, E92Q, and T66I and demonstrate that they confer
      a reduction in susceptibility not only to elvitegravir but also to raltegravir
      (MK-0518) and other integrase inhibitors. The locations of the mutations are
      highlighted in the catalytic sites of integrase, and we correlate the mutations
      with expected drug-protein contacts. In addition, mutations that do not confer
      reduced susceptibility when present alone (H114Y, L74M, R20K, A128T, E138K, and
      S230R) are also discussed in relation to their position in the catalytic core
      domain and their proximity to known structural features of integrase. These data
      broaden the understanding of antiviral resistance against integrase inhibitors
      and may give insight facilitating the discovery of second-generation compounds.

PMID- 18715921
TI  - A genetic interaction between hepatitis C virus NS4B and NS3 is important for RNA
      replication.
AB  - Hepatitis C virus (HCV) nonstructural protein 4B (NS4B), a poorly characterized
      integral membrane protein, is thought to function as a scaffold for replication
      complex assembly; however, functional interactions with the other HCV
      nonstructural proteins within this complex have not been defined. We report that
      a Con1 chimeric subgenomic replicon containing the NS4B gene from the closely
      related H77 isolate is defective for RNA replication in a transient assay,
      suggesting that H77 NS4B is unable to productively interact with the Con1
      replication machinery. The H77 NS4B sequences that proved detrimental for Con1
      RNA replication resided in the predicted N- and C-terminal cytoplasmic domains as
      well as the central transmembrane region. Selection for Con1 derivatives that
      could utilize the entire H77 NS4B or hybrid Con1-H77 NS4B proteins yielded
      mutants containing single amino acid substitutions in NS3 and NS4A. The second
      site mutations in NS3 partially restored the replication of Con1 chimeras
      containing the N-terminal or transmembrane domains of H77 NS4B. In contrast, the
      deleterious H77-specific sequences in the C terminus of NS4B, which mapped to a
      cluster of four amino acids, were completely suppressed by second-site
      substitutions in NS3. Collectively, these results provide the first evidence for
      a genetic interaction between NS4B and NS3 important for productive HCV RNA
      replication.

PMID- 18715922
TI  - Structural rearrangement within an enveloped virus upon binding to the host cell.
AB  - We have made the surprising discovery that the interactions of herpes simplex
      virus with its initial cell attachment receptor induce a rapid and highly
      efficient structural change in the tegument, the region of the virion situated
      between the membrane and the capsid. It has been known for nearly a decade that
      viruses can trigger host signaling pathways when they bind to receptors on the
      cell surface; however, until now there has been no evidence that a signal can be
      sent in reverse--from the "outside in"--across a viral membrane. Evidence for
      this signaling event was found during studies of UL16, a tegument protein that is
      conserved among all the herpesviruses. Previous work has demonstrated that UL16
      is bound to capsids isolated from the cytoplasm of infected cells, but this
      interaction is destabilized during subsequent egress steps, leading to release of
      the extracellular virion. Pretreatment with N-ethylmaleimide, a small, membrane
      permeating compound that covalently modifies free cysteines, restabilizes the
      interaction, thereby permitting the capsid-UL16 complex to be isolated following
      disruption of virions with NP-40. In the experiments described here, we found
      that the natural signal for release of UL16 from capsids is sent when virions
      merely bind to cells at 4 degrees C. The internal change was also observed upon
      binding to immobilized heparin in a manner that requires viral glycoprotein C.
      This represents the first example of signaling across a viral envelope following
      receptor binding.

PMID- 18715923
TI  - Differential modulation of prM cleavage, extracellular particle distribution, and
      virus infectivity by conserved residues at nonfurin consensus positions of the
      dengue virus pr-M junction.
AB  - In the generation of flavivirus particles, an internal cleavage of the envelope
      glycoprotein prM by furin is required for the acquisition of infectivity. Unlike
      cleavage of the prM of other flaviviruses, cleavage of dengue virus prM is
      incomplete in many cell lines; the partial cleavage reflects the influence of
      residues at furin nonconsensus positions of the pr-M junction, as flaviviruses
      share basic residues at positions P1, P2, and P4, recognized by furin. In this
      study, viruses harboring the alanine-scanning and other multiple-point mutations
      of the pr-M junction were generated, employing a dengue virus background that
      exhibited 60 to 70% prM cleavage and a preponderance of virion-sized
      extracellular particles. Analysis of prM and its cleavage products in viable
      mutants revealed a cleavage-suppressive effect at the conserved P3 Glu residue,
      as well as the cleavage-augmenting effects at the P5 Arg and P6 His residues,
      indicating an interplay between opposing modulatory influences mediated by these
      residues on the cleavage of the pr-M junction. Changes in the prM cleavage level
      were associated with altered proportions of extracellular virions and subviral
      particles; mutants with reduced cleavage were enriched with subviral particles
      and prM-containing virions, whereas the mutant with enhanced cleavage was
      deprived of these particles. Alterations of virus multiplication were detected in
      mutants with reduced prM cleavage and were correlated with their low specific
      infectivities. These findings define the functional roles of charged residues
      located adjacent to the furin consensus sequence in the cleavage of dengue virus
      prM and provide plausible mechanisms by which the reduction in the pr-M junction
      cleavability may affect virus replication.

PMID- 18715924
TI  - E6 proteins from multiple human betapapillomavirus types degrade Bak and protect
      keratinocytes from apoptosis after UVB irradiation.
AB  - Human papillomavirus (HPV) types from the beta genus (beta-HPVs) have been
      implicated in the development of skin cancer. A potentially important aspect of
      their carcinogenic role is the ability of the E6 protein to degrade the
      proapoptotic family member Bak, which gives cells the ability to survive UV
      damage. However, it is unknown if the ability to degrade Bak is limited to
      certain beta-HPV types or whether E6 expression in keratinocytes affects other
      proteins important for apoptosis signaling. We tested the abilities of E6
      proteins from several representative members of the beta-HPVs to degrade Bak and
      protect UV-treated keratinocytes from apoptosis. The E6 proteins of the beta-HPV
      type 5 (HPV5), -8, -20, -22, -38, -76, -92, and -96, as well as the alpha genus
      HPV HPV16, all degraded Bak or prevented its accumulation following UV treatment
      but did not degrade Bak constitutively. In addition, when tested using HPV16 E6
      (16E6) and 8E6 as representative E6 proteins from the alpha and beta genera,
      respectively, Bak degradation was dependent on the E3 ubiquitin ligase, E6AP.
      Other important regulators of apoptotic signaling were examined and found to be
      unperturbed by the expression of the beta-HPV E6 proteins. Importantly, the
      expression of beta-HPV E6 proteins protected keratinocytes from apoptosis to the
      same extent as 16E6-expressing cells. In conclusion, several of the beta-HPV
      types possess the ability to protect UV-treated keratinocytes from apoptosis by
      reducing levels of Bak in those cells, thus blocking the intrinsic apoptotic
      pathway.

PMID- 18715925
TI  - Hidden virulence determinants in a viral quasispecies in vivo.
AB  - The characterization of virulence determinants of pathogenic agents is of utmost
      relevance for the design of disease control strategies. So far, two classes of
      virulence determinants have been characterized for viral populations: those
      imprinted in the nucleotide sequence of some specific genomic regions and those
      that depend on the complexity of the viral population as such. Here we provide
      evidence of a virulence determinant that depends neither on a genomic sequence
      nor on detectable differences in population complexity. Foot-and-mouth disease
      virus is lethal for C57BL/6 mice showing the highest viral load in pancreas.
      Virus isolated from pancreas after one passage in mice showed an attenuated
      phenotype, with no lethality even at the highest dose tested. By contrast, virus
      from sera of the same mice displayed a virulence similar to that of the parental
      wild-type clone and virus isolated from spleen displayed an intermediate
      phenotype. However, viral populations from pancreas, spleen, and serum showed
      indistinguishable consensus genomic nucleotide sequences and mutant spectrum
      complexities, as quantified according to the mutation frequencies of both entire
      genomic nucleotide sequences of biological clones. The results show that the
      populations with differing virulences cannot be distinguished either by the
      consensus sequence or by the average complexity of the mutant spectrum.
      Differential harvesting of virus generated by cell transfection of RNA from serum
      and pancreas failed to reveal genetic differences between subpopulations endowed
      with differing virulences. In addition to providing evidence of hidden virulence
      determinants, this study underlines the capacity of a clone of an RNA virus to
      rapidly diversify phenotypically in vivo.

PMID- 18715926
TI  - Kinetic analysis by real-time PCR of hepatitis C virus (HCV)-specific T cells in
      peripheral blood and liver after challenge with HCV.
AB  - Intrahepatic virus-specific CD8(+) T cells are thought to be important for the
      control of hepatitis C virus (HCV) infection, yet the precise kinetics for the
      expansion of epitope-specific T cells over the course of infection are difficult
      to determine with currently available methods. We used a real-time PCR assay to
      measure the frequency of clonotypic HCV-specific CD8(+) T cells in peripheral
      blood and snap-frozen liver biopsy specimens of two chimpanzees (Pan troglodytes)
      with previously resolved HCV infection who were rechallenged with HCV. In
      response to rechallenge, the magnitude of each clonotypic response was 10-fold
      higher in the liver than in the blood, and the peak clonotype frequency was
      concurrent with the peak viral load. The higher frequency of HCV-specific
      clonotypes in the liver than in peripheral blood was maintained for at least 3
      months after the clearance of viremia. After antibody-mediated CD8(+) T-cell
      depletion and another viral challenge, the rebound of these clonotypes was seen
      prior to an appreciable reconstitution of CD8(+) T-cell values and, again, at
      higher frequencies in the liver than in peripheral blood. These data demonstrate
      the importance of intrahepatic virus-specific CD8(+) T cells for the clearance of
      infection and the rapid kinetics of expansion after virus challenge.

PMID- 18715927
TI  - Hepatitis C virus-specific T-cell gamma interferon and proliferative responses
      are more common in perihepatic lymph nodes than in peripheral blood or liver.
AB  - The activation state, differentiation state, and functions of liver lymphocytes
      and perihepatic lymph nodes during chronic hepatitis C virus (HCV) infection are
      not well understood. Here, we performed phenotypic and functional analyses of
      freshly prepared lymphocytes isolated from the livers, perihepatic lymph nodes,
      and peripheral blood compartments of chronic HCV-infected and disease control
      subjects with end-stage liver disease undergoing liver transplantation. We
      measured lymphocyte subset frequency and memory T-cell gamma interferon (IFN
      gamma) and proliferative responses to HCV peptide and control viral antigens in
      direct ex vivo assays. We found higher frequencies of CD4 cells in the lymph node
      compartment than in the other compartments for both HCV-infected and disease
      control subjects. Lymph node CD4 and CD8 cells less commonly expressed the
      terminal differentiation marker CD57, a finding consistent with an earlier
      differentiation state. In HCV-infected subjects, HCV-specific IFN-gamma-producing
      and proliferative responses were commonly observed in the lymph node fraction,
      while they were uncommonly observed in the peripheral blood or liver fractions.
      In contrast, control viral CD4 protein antigen and CD8 peptide antigen-specific
      IFN-gamma responses were commonly observed in the periphery and uncommonly
      observed in the lymph nodes of these same subjects. These findings are consistent
      with a selective defect in HCV-specific T-cell effector function or distribution
      in patients with advanced chronic HCV infection. The high frequency of HCV
      reactive T cells in perihepatic lymph nodes indicates that a failure to generate
      or sustain T-lymphocyte HCV reactivity is not responsible for the paucity of
      functional cells even in end-stage liver disease.

PMID- 18715928
TI  - AKT1-dependent activation of NF-kappaB by the L protein of parainfluenza virus 5.
AB  - Innate immunity plays a critical role in the control of viral infections. The
      induction of innate immune responses requires activation of transcription
      factors. In particular, NF-kappaB plays an essential role in activating the
      expression of cytokines involved in innate immunity such as beta interferon (IFN
      beta) and interleukin-6 (IL-6). However, the mechanisms by which viruses activate
      NF-kappaB are poorly defined. Infection by parainfluenza virus 5 (PIV5), a
      prototypical member of the Paramyxoviridae family of Mononegavirales, has been
      shown to activate the expression of IFN-beta and IL-6. To examine how PIV5
      induces this expression, we have examined the activation of NF-kappaB by PIV5
      proteins. We have found that expression of PIV5 L protein alone is sufficient to
      activate NF-kappaB. The L protein of PIV5, the catalytic component of the viral
      RNA-dependent RNA polymerase, contains six domains that are conserved among all
      negative-stranded nonsegmented RNA viruses. We have mapped the region that
      activates NF-kappaB to the second domain, which is thought to be involved in RNA
      synthesis. The activation of NF-kappaB by L requires AKT1, a serine/threonine
      kinase, since AKT1 small interfering RNA, an AKT inhibitor as well as a dominant
      negative mutant of AKT1, blocks this activation. Furthermore, we have found that
      L interacts with AKT1 and enhances its phosphorylation. We speculate that L may
      encode AKT1 kinase activity.

PMID- 18715929
TI  - Structural characterization of the 1918 influenza virus H1N1 neuraminidase.
AB  - Influenza virus neuraminidase (NA) plays a crucial role in facilitating the
      spread of newly synthesized virus in the host and is an important target for
      controlling disease progression. The NA crystal structure from the 1918 "Spanish
      flu" (A/Brevig Mission/1/18 H1N1) and that of its complex with zanamivir
      (Relenza) at 1.65-A and 1.45-A resolutions, respectively, corroborated the
      successful expression of correctly folded NA tetramers in a baculovirus
      expression system. An additional cavity adjacent to the substrate-binding site is
      observed in N1, compared to N2 and N9 NAs, including H5N1. This cavity arises
      from an open conformation of the 150 loop (Gly147 to Asp151) and appears to be
      conserved among group 1 NAs (N1, N4, N5, and N8). It closes upon zanamivir
      binding. Three calcium sites were identified, including a novel site that may be
      conserved in N1 and N4. Thus, these high-resolution structures, combined with our
      recombinant expression system, provide new opportunities to augment the limited
      arsenal of therapeutics against influenza.

PMID- 18715930
TI  - Avian influenza h6 viruses productively infect and cause illness in mice and
      ferrets.
AB  - Influenza pandemic preparedness has focused on influenza virus H5 and H7
      subtypes. However, it is not possible to predict with certainty which subtype of
      avian influenza virus will cause the next pandemic, and it is prudent to include
      other avian influenza virus subtypes in pandemic preparedness efforts. An H6
      influenza virus was identified as a potential progenitor of the H5N1 viruses that
      emerged in Hong Kong in 1997. This virus continues to circulate in the bird
      population in Asia, and other H6 viruses are prevalent in birds in North America
      and Asia. The high rate of reassortment observed in influenza viruses and the
      prevalence of H6 viruses in birds suggest that this subtype may pose a pandemic
      risk. Very little is known about the replicative capacity, immunogenicity, and
      correlates of protective immunity for low-pathogenicity H6 influenza viruses in
      mammals. We evaluated the antigenic and genetic relatedness of 14 H6 influenza
      viruses and their abilities to replicate and induce a cross-reactive immune
      response in two animal models: mice and ferrets. The different H6 viruses
      replicated to different levels in the respiratory tracts of mice and ferrets,
      causing varied degrees of morbidity and mortality in these two models. H6 virus
      infection induced similar patterns of neutralizing antibody responses in mice and
      ferrets; however, species-specific differences in the cross-reactivity of the
      antibody responses were observed. Overall, cross-reactivity of neutralizing
      antibodies in H6 virus-infected mice did not correlate well with protection
      against heterologous wild-type H6 viruses. However, we have identified an H6
      virus that induces protective immunity against viruses in the North American and
      Eurasian lineages.

PMID- 18715931
TI  - Epstein-barr virus encodes three bona fide ubiquitin-specific proteases.
AB  - Manipulation of the ubiquitin proteasome system (UPS) is emerging as a common
      theme in viral pathogenesis. Some viruses have been shown to encode functional
      homologs of UPS enzymes, suggesting that a systematic identification of these
      products may provide new insights into virus-host cell interactions. Ubiquitin
      specific proteases, collectively known as deubiquitinating enzymes (DUBs),
      regulate the activity of the UPS by hydrolyzing ubiquitin peptide or isopeptide
      bonds. The prediction of viral DUBs based on sequence similarity with known
      enzymes is hampered by the diversity of viral genomes. In this study sequence
      alignments, pattern searches, and hidden Markov models were developed for the
      conserved C- and H-boxes of the known DUB families and used to search the open
      reading frames (ORFs) of Epstein-Barr virus (EBV), a large gammaherpesvirus that
      has been implicated in the pathogenesis of a broad spectrum of human malignancies
      of lymphoid and epithelial cell origin. The searches identified a limited number
      of EBV ORFs that contain putative DUB catalytic domains. DUB activity was
      confirmed by functional assays and mutation analysis for three high scoring
      candidates, supporting the usefulness of this bioinformatics approach in
      predicting distant homologues of cellular enzymes.

PMID- 18715933
TI  - Minority human immunodeficiency virus type 1 variants in antiretroviral-naive
      persons with reverse transcriptase codon 215 revertant mutations.
AB  - T215 revertant mutations such as T215C/D/E/S that evolve from the nucleoside
      reverse transcriptase (RT) inhibitor mutations T215Y/F have been found in about
      3% of human immunodeficiency virus type 1 (HIV-1) isolates from newly diagnosed
      HIV-1-infected persons. We used a newly developed sequencing method-ultradeep
      pyrosequencing (UDPS; 454 Life Sciences)--to determine the frequency with which
      T215Y/F or other RT inhibitor resistance mutations could be detected as minority
      variants in samples from untreated persons that contain T215 revertants
      ("revertant" samples) compared with samples from untreated persons that lack such
      revertants ("control" samples). Among the 22 revertant and 29 control samples,
      UDPS detected a mean of 3.8 and 4.8 additional RT amino acid mutations,
      respectively. In 6 of 22 (27%) revertant samples and in 4 of 29 control samples
      (14%; P = 0.4), UDPS detected one or more RT inhibitor resistance mutations.
      T215Y or T215F was not detected in any of the revertant or control samples;
      however, 4 of 22 revertant samples had one or more T215 revertants that were
      detected by UDPS but not by direct PCR sequencing. The failure to detect viruses
      with T215Y/F in the 22 revertant samples in this study may result from the
      overwhelming replacement of transmitted T215Y variants by the more fit T215
      revertants or from the primary transmission of a T215 revertant in a subset of
      persons with T215 revertants.

PMID- 18715932
TI  - Vaccinia virus subverts a mitochondrial antiviral signaling protein-dependent
      innate immune response in keratinocytes through its double-stranded RNA binding
      protein, E3.
AB  - Skin keratinocytes provide a first line of defense against invading
      microorganisms in two ways: (i) by acting as a physical barrier to pathogen entry
      and (ii) by initiating a vigorous innate immune response upon sensing danger
      signals. How keratinocytes detect virus infections and generate antiviral immune
      responses is not well understood. Orthopoxviruses are dermatotropic DNA viruses
      that cause lethal disease in humans. Virulence in animal models depends on the
      virus-encoded bifunctional Z-DNA/double-stranded RNA (dsRNA)-binding protein E3.
      Here, we report that infection of mouse primary keratinocytes with a vaccinia
      DeltaE3L mutant virus triggers the production of beta interferon (IFN-beta),
      interleukin-6 (IL-6), CCL4, and CCL5. None of these immune mediators is produced
      by keratinocytes infected with wild-type vaccinia virus. The dsRNA-binding domain
      of E3 suffices to prevent activation of the innate immune response. DeltaE3L
      induction of IFN-beta, IL-6, CCL4, and CCL5 secretion requires mitochondrial
      antiviral signaling protein (MAVS; an adaptor for the cytoplasmic viral RNA
      sensors RIG-I and MDA5) and the transcription factor IRF3. IRF3 phosphorylation
      is induced in keratinocytes infected with DeltaE3L, an event that depends on
      MAVS. The response of keratinocytes to DeltaE3L is unaffected by genetic ablation
      of Toll-like receptor 3 (TLR3), TRIF, TLR9, and MyD88.

PMID- 18715934
TI  - Persistent propagation of variant Creutzfeldt-Jakob disease agent in murine
      spleen stromal cell culture with features of mesenchymal stem cells.
AB  - The transmission of variant Creutzfeldt-Jakob disease (vCJD) through blood
      transfusions has created new concerns about the iatrogenic spread of
      transmissible spongiform encephalopathies (TSEs)/prion diseases through blood and
      plasma-derived products and has increased the need to develop efficient methods
      for detection of the agent in biologics. Here, we report the first successful
      generation of spleen-derived murine stromal cell cultures that persistently
      propagate two mouse-adapted isolates of human TSE agents, mouse-adapted vCJD, and
      Fukuoka 1. These new cell cultures can be used efficiently for studies of the
      pathogenesis of the disease, for development of diagnostics and therapeutics, and
      as a rapid ex vivo assay for TSE inactivation/removal procedures.

PMID- 18715935
TI  - Open reading frame 2, encoded by the latency-related gene of bovine herpesvirus
      1, has antiapoptotic activity in transiently transfected neuroblastoma cells.
AB  - The latency-related (LR) RNA encoded by bovine herpesvirus 1 is abundantly
      expressed in the trigeminal ganglia of latently infected calves. Expression of LR
      proteins is necessary for reactivation from latency and the protection of
      infected neurons from apoptosis. In this study, we demonstrated that an LR
      encoded protein, open reading frame 2 (ORF-2), or ORF-2 fusion proteins encoded
      by alternatively spliced LR transcripts inhibit cold shock or Fas ligand-induced
      apoptosis in mouse neuroblastoma (neuro-2A) cells. Frameshift mutants of ORF-2 do
      not inhibit apoptosis, which suggests that protein expression, not LR RNA
      expression, mediates the antiapoptotic activity of the LR gene in transfected
      neuro-2A cells.

PMID- 18715936
TI  - hTERT alone immortalizes epithelial cells of renal proximal tubules without
      changing their functional characteristics.
AB  - Telomere-dependent replicative senescence is one of the mechanisms that limit the
      number of population doublings of normal human cells. By overexpression of
      telomerase, cells of various origins have been successfully immortalized without
      changing the phenotype. While a limited number of telomerase-immortalized cells
      of epithelial origin are available, none of renal origin has been reported so
      far. Here we have established simple and safe conditions that allow serial
      passaging of renal proximal tubule epithelial cells (RPTECs) until entry into
      telomere-dependent replicative senescence. As reported for other cells,
      senescence of RPTECs is characterized by arrest in G1 phase, shortened telomeres,
      staining for senescence-associated beta-galactosidase, and accumulation of gamma
      H2AX foci. Furthermore, ectopic expression of the catalytic subunit of telomerase
      (TERT) was sufficient to immortalize these cells. Characterization of
      immortalized RPTEC/TERT1 cells shows characteristic morphological and functional
      properties like formation of tight junctions and domes, expression of
      aminopeptidase N, cAMP induction by parathyroid hormone, sodium-dependent
      phosphate uptake, and the megalin/cubilin transport system. No genomic
      instability within up to 90 population doublings has been observed. Therefore,
      these cells are proposed as a valuable model system not only for cell biology but
      also for toxicology, drug screening, biogerontology, as well as tissue
      engineering approaches.

PMID- 18715937
TI  - Evidence for increased postprandial distal nephron calcium delivery in
      hypercalciuric stone-forming patients.
AB  - A main mechanism of idiopathic hypercalciuria (IH) in calcium stone-forming
      patients (IHSF) is postprandial reduction of renal tubule calcium reabsorption
      that cannot be explained by selective reduction of serum parathyroid hormone
      levels; the nephron site(s) responsible are not as yet defined. Using fourteen 1
      h measurements of the clearances of sodium, calcium, and endogenous lithium
      during a three-meal day in the University of Chicago General Clinical Research
      Center, we found reduced postprandial proximal tubule reabsorption of sodium and
      calcium in IHSF vs. normal subjects. The increased distal sodium delivery is
      matched by increased distal reabsorption so that urine sodium excretions do not
      differ, but distal calcium reabsorption does not increase enough to match
      increased calcium delivery, so hypercalciuria results. In fact, urine calcium
      excretion and overall renal fractional calcium reabsorption both are high in IHSF
      vs. normal when adjusted for distal calcium delivery, strongly suggesting a
      distal as well as proximal reduction of calcium reabsorption. The combination of
      reduced proximal tubule and distal nephron calcium reabsorption in IHSF is a new
      finding and indicates that IH involves a complex, presumably genetic, variation
      of nephron function. The increased calcium delivery into the later nephron may
      play a role in stone formation via deposition of papillary interstitial apatite
      plaque.

PMID- 18715938
TI  - A mathematical model of distal nephron acidification: diuretic effects.
AB  - Through their action on the distal nephron (DN), diuretics may produce systemic
      acid-base disturbances: metabolic alkalosis with thiazides or loop diuretics and
      metabolic acidosis with amiloride. Enhanced acid excretion may be due to a local
      effect on the diuretic target cell (a shift of Na+ reabsorption from NaCl
      transport to Na+/H+ exchange), or an effect at a distance: namely, increases in
      luminal fluid flow or luminal Na+ concentration may enhance more distal proton
      secretion. Both local and distance effects are supported by micropuncture data.
      In the present work, mathematical models of the distal convoluted tubule
      (DCT)/connecting tubule (CNT) (Weinstein AM, Am J Physiol Renal Physiol 289: F721
      F741, 2005), and cortical and medullary collecting ducts (CD) (Weinstein AM, Am J
      Physiol Renal Physiol 283: F1237-F1251, 2002) have been concatenated to yield a
      model of rat DN. Among the segments of this DN, the DCT-CNT is responsible for
      the major portion of distal acidification. Predictions from the model
      calculations include the following. 1) With increasing distal Na+ delivery, there
      is little change in net acid excretion, but a shift in acidification locus from
      shared DCT and CNT contributions, to DCT prominence. 2) Urinary acidification by
      thiazides is primarily local (in the DCT) via the shift in Na+ reabsorption from
      NaCl cotransport to entry via NHE2. Increased NaCl delivery to the CNT increases
      beta-cell HCO3(-) secretion, and thus blunts urine acidification. 3) In contrast
      to conclusions drawn from the isolated CD model, inclusion of the CNT now
      reproduces the observed distal acidification defect found with ENaC block, so
      that this action of amiloride appears to be sufficient to produce "voltage
      dependent" distal renal tubular acidosis. 4) The effect of furosemide to enhance
      distal urinary acidification is not reproduced by the model without major
      upregulation of CNT alpha-cell transport, perhaps as a result of increased
      luminal flow.

PMID- 18715939
TI  - Heme oxygenase metabolites inhibit tubuloglomerular feedback (TGF).
AB  - Tubuloglomerular feedback (TGF) is the mechanism by which the macula densa (MD)
      senses increases in luminal NaCl concentration and sends a signal to constrict
      the afferent arteriole (Af-Art). The kidney expresses constitutively heme
      oxygenase-2 (HO-2) and low levels of HO-1. HOs release carbon monoxide (CO),
      biliverdin, and free iron. We hypothesized that renal HOs inhibit TGF via release
      of CO and biliverdin. Rabbit Af-Arts and attached MD were simultaneously
      microperfused in vitro. The TGF response was determined by measuring Af-Art
      diameter before and after increasing NaCl in the MD perfusate. When HO activity
      was inhibited by adding stannous mesoporphyrin (SnMP) to the MD perfusate, the
      TGF response increased from 2.1+/-0.2 to 4.1+/-0.4 microm (P=0.003, control vs.
      SnMP, n=7). When a CO-releasing molecule, (CORM-3; 50 microM), was added to the
      MD perfusate, the TGF response decreased by 41%, from 3.6+/-0.3 to 2.1+/-0.2
      microm (P<0.001, control vs. CORM-3, n=12). When CORM-3 at 100 microM was added
      to the perfusate, it completely blocked the TGF response, from 4.2+/-0.4 to 
      0.2+/-0.3 microm (P<0.001, control vs. CORM-3, n=6). When biliverdin was added to
      the perfusate, the TGF response decreased by 79%, from 3.4+/-0.3 to 0.7+/-0.4
      microm (P=0.001, control vs. biliverdin, n=6). The effects of SnMP and CORM-3
      were not blocked by inhibition of nitric oxide synthase. We concluded that renal
      HO inhibits TGF probably via release of CO and biliverdin. HO regulation of TGF
      is a novel mechanism that could lead to a better understanding of the control of
      renal microcirculation and function.

PMID- 18715940
TI  - Urea transporters UT-A1 and UT-A3 accumulate in the plasma membrane in response
      to increased hypertonicity.
AB  - The UT-A1 and UT-A3 urea transporters are expressed in the terminal inner
      medullary collecting duct (IMCD) and play an important role in the production of
      concentrated urine. We showed that both hyperosmolarity and vasopressin increase
      urea permeability in perfused rat terminal IMCDs and that UT-A1 and UT-A3
      accumulate in the plasma membrane in response to vasopressin. In this study, we
      investigated whether hyperosmolarity causes UT-A1 and/or UT-A3 to accumulate in
      the plasma membrane or represents a complimentary stimulatory pathway. Rat IMCD
      suspensions were incubated in 450 vs. 900 mosM solutions. We biotinylated the
      IMCD surface proteins, collected, and analyzed them. Membrane accumulation was
      assessed by Western blotting of the biotinylated protein pool probed with anti-UT
      A1 or anti-UT-A3. We studied the effect of NaCl, urea, and sucrose as osmotic
      agents. Membrane-associated UT-A1 and UT-A3 increased relative to control levels
      when either NaCl (UT-A1 increased 37 +/- 6%; UT-A3 increased 46 +/- 13%) or
      sucrose (UT-A1 increased 81 +/- 13%; UT-A3 increased 60 +/- 8%) was used to
      increase osmolarity. There was no increase in membrane UT-A1 or UT-A3 when urea
      was added. Analogously, UT-A1 phosphorylation was increased in NaCl- and sucrose-
      but not in urea-based hyperosmolar solutions. Hypertonicity also increased UT-A3
      phosphorylation. We conclude that the increase in the urea permeability in
      response to hyperosmolarity reflects both UT-A1 and UT-A3 movement to the plasma
      membrane and may be a direct response to tonicity. Furthermore, this movement is
      accompanied by, and may require, increased phosphorylation in response to
      hypertonicity.

PMID- 18715941
TI  - V2 vasopressin receptor deficiency causes changes in expression and function of
      renal and hypothalamic components involved in electrolyte and water homeostasis.
AB  - Polyuria, hypernatremia, and hypovolemia are the major clinical signs of
      inherited nephrogenic diabetes insipidus (NDI). Hypernatremia is commonly
      considered a secondary sign caused by the net loss of water due to insufficient
      insertion of aquaporin-2 water channels into the apical membrane of the
      collecting duct cells. In the present study, we employed transcriptome-wide
      expression analysis to study gene expression in V2 vasopressin receptor (Avpr2)
      deficient mice, an animal model for X-linked NDI. Gene expression changes in NDI
      mice indicate increased proximal tubular sodium reabsorption. Expression of
      several key genes including Na+-K+-ATPase and carbonic anhydrases was increased
      at the mRNA levels and accompanied by enhanced enzyme activities. In addition,
      altered expression was also observed for components of the eicosanoid and thyroid
      hormone pathways, including cyclooxygenases and deiodinases, in both kidney and
      hypothalamus. These effects are likely to contribute to the clinical NDI
      phenotype. Finally, our data highlight the involvement of the renin-angiotensin
      aldosterone system in NDI pathophysiology and provide clues to explain the
      effectiveness of diuretics and indomethacin in the treatment of NDI.

PMID- 18715942
TI  - Renal function and structure in a rat model of arterial calcification and
      increased pulse pressure.
AB  - Clinical studies suggest a strong link between tissue calcification and pressure
      hyperpulsatility in end stage renal disease patients. Using a Wistar rat model of
      arterial elastocalcinosis and hyperpulsatility [vitamin D and nicotine (VDN)
      treatment], we evaluated the relative importance of tissue calcification and
      hyperpulsatility in the etiology of renal failure. VDN rats showed significant
      increases in aortic wall calcium content (50 times; 992+/-171 vs. control 19+/-1
      micromol/g dry wt) and pulse pressure (1.5 times; 61+/-4 vs. control 40+/-2
      mmHg). Significant renal calcification (16 times; 124+/-27 vs. control 8.1+/-0.7
      micromol/g dry wt) occurred mainly within the media of the preglomerular
      vasculature and in the areas of interstitial fibrosis in VDN. Extensive renal
      damages (5 times; 26+/-5% of collapsed-atrophic or sclerotic glomeruli, or
      glomerular cysts vs. control 5.2+/-0.3%; 28 times; 61+/-12% areas of focal,
      cortical areas exhibiting interstitial fibrosis per section vs. control 2.2+/
      0.6%) were observed histologically. The glomerular filtration rate significantly
      decreased (880+/-40 vs. control 1,058+/-44 microl.min(-1).g kidney wt(-1)).
      Albuminuria increased six times (1.6+/-0.4 vs. control 0.27+/-0.04 mg/24 h).
      There were significant linear relationships between albuminuria and pulse
      pressure (r2=0.408; n=24) or renal calcium content (r2=0.328; n=24; P<0.05) and
      between glomerular filtration rate and pulse pressure (r2=0.168; n=27). To our
      knowledge, this study provides the first evidence of links between both 1)
      hyperpulsatility and renal dysfunction, and 2) renal calcification and renal
      dysfunction. Given the increasing frequency of end-stage renal disease, this
      model could prove useful for preclinical evaluation of drugs that prevent or
      attenuate hyperpulsatility and/or tissue calcification.

PMID- 18715943
TI  - Dissociation of NEPH1 from nephrin is involved in development of a rat model of
      focal segmental glomerulosclerosis.
AB  - Focal segmental glomerulosclerosis (FSGS) is a disease showing severe
      proteinuria, and the disease progresses to end-stage kidney failure in many
      cases. However, the pathogenic mechanism of FSGS is not well understood. The slit
      diaphragm (SD), which bridges the neighboring foot processes of glomerular
      epithelial cells, is understood to function as a barrier of the glomerular
      capillary wall. To investigate the role of SD dysfunction in the development of
      FSGS, we analyzed the expression of SD-associated molecules in rat adriamycin
      induced nephropathy, a mimic of FSGS. The staining of the SD molecules nephrin,
      podocin, and NEPH1 had already shifted to a discontinuous dotlike pattern at the
      initiation phase of the disease, when neither proteinuria nor any morphological
      alterations were detected yet. The alteration of NEPH1 expression was the most
      evident among the molecules examined, and NEPH1 was dissociated from nephrin at
      the initiation phase. On day 28, when severe proteinuria was detected and
      sclerotic changes were already observed, alteration of the expressions of
      nephrin, podocin, and NEPH1 worsened, but no alteration in the expression of
      other SD-associated molecules or other podocyte molecules was detected. It is
      postulated that the dissociation of NEPH1 from nephrin initiates proteinuria and
      that the SD alteration restricted in these molecules plays a critical role in the
      development of sclerotic changes in FSGS.

PMID- 18715944
TI  - Genomic and nongenomic dose-dependent biphasic effect of aldosterone on Na+/H+
      exchanger in proximal S3 segment: role of cytosolic calcium.
AB  - The effects of aldosterone on the intracellular pH recovery rate (pHirr) via
      Na+/H+ exchanger and on the [Ca2+]i were investigated in isolated rat S3 segment.
      Aldosterone [10(-12), 10(-10), or 10(-8) M with 1-h, 15- or 2-min preincubation
      (pi)] caused a dose-dependent increase in the pHirr, but aldosterone (10(-6) M
      with 1-h, 15- or 2-min pi) decreased it (these effects were prevented by HOE694
      but not by S3226). After 1 min of aldosterone pi, there was a transient and dose
      dependent increase of the [Ca2+]i and after 6-min pi there was a new increase of
      [Ca2+]i that persisted after 1 h. Spironolactone, actinomycin D, or cycloheximide
      did not affect the effects of aldosterone (15- or 2-min pi) but inhibited the
      effects of aldosterone (1-h pi) on pHirr and on [Ca2+]i. RU 486 prevented the
      stimulatory effect of aldosterone (10(-12) M, 15- or 2-min pi) on both parameters
      and maintained the inhibitory effect of aldosterone (10(-6) M, 15- or 2-min pi)
      on the pHirr but reversed its stimulatory effect on the [Ca2+]i to an inhibitory
      effect. The data indicate a genomic (1 h, via MR) and a nongenomic action (15 or
      2 min, probably via GR) on [Ca2+]i and on the basolateral NHE1 and are compatible
      with stimulation of the NHE1 by increases in [Ca2+]i in the lower range (at 10(
      12) M aldosterone) and inhibition by increases at high levels (at 10(-6) M
      aldosterone) or decreases in [Ca2+]i (at 10(-6) M aldosterone plus RU 486).

PMID- 18715945
TI  - Mitochondrial respiratory enzyme complexes in rostral ventrolateral medulla as
      cellular targets of nitric oxide and superoxide interaction in the antagonism of
      antihypertensive action of eNOS transgene.
AB  - Overproduction of nitric oxide (NO) by gene transduction of endothelial NO
      synthase (eNOS) in rostral ventrolateral medulla (RVLM), which is responsible for
      maintenance of vasomotor tone, reduces arterial pressure in spontaneously
      hypertensive rats (SHR). This NO-induced vasodepression, however, is not
      sustained and is followed by rebound hypertension. Because superoxide anion
      (O(2)(*-)) level is increased and synthesis or activity of mitochondrial
      manganese superoxide dismutase (SOD2) is reduced in RVLM during hypertension, we
      hypothesized that an interaction between NO and O(2)(*-) in RVLM, using
      mitochondrial respiratory enzyme complexes (MRC) as the cellular target,
      contributes to those cardiovascular outcomes after eNOS gene transduction in SHR.
      The present study assessed this hypothesis using adenoviral vectors to
      overexpress eNOS (AdeNOS) and/or SOD2 (AdSOD2) in RVLM of SHR or normotensive
      Wistar-Kyoto (WKY) rats. Microinjection of AdeNOS bilaterally into RVLM elicited
      35% depression of MRC-I enzyme activity and evoked 60% and 50% increase in O(2)(*
      ) and peroxynitrite level in RVLM of SHR, but not WKY rats, which was reversed by
      cotransduced AdSOD2 or treatment with peroxynitrite decomposition catalyst.
      Cotransduction of AdeNOS and AdSOD2 in RVLM of SHR elicited significantly greater
      decreases in arterial pressure and heart rate than those promoted by the
      individual transgene and prevented the AdeNOS-induced rebound hypertension. We
      conclude that an interactive action between NO and O(2)(*-) on MRC-I in RVLM via
      formation of peroxynitrite contributes to the unsustained hypotensive effects of
      NO after overexpression of eNOS in SHR. The mitochondria-derived O(2)(*-) also
      mediates the rebound hypertension induced by eNOS transgene in RVLM of SHR.

PMID- 18715946
TI  - GATA transcription factors integrate Wnt signalling during heart development.
AB  - Cardiogenesis is inhibited by canonical Wnt/beta-catenin signalling and
      stimulated by non-canonical Wnt11/JNK signalling, but how these two signalling
      pathways crosstalk is currently unknown. Here, we show that Wnt/beta-catenin
      signalling restricts cardiogenesis via inhibition of GATA gene expression, as
      experimentally reinstating GATA function overrides beta-catenin-mediated
      inhibition and restores cardiogenesis. Furthermore, we show that GATA
      transcription factors in turn directly regulate Wnt11 gene expression, and that
      Wnt11 is required to a significant degree for mediating the cardiogenesis
      promoting function of GATA transcription factors. These results demonstrate that
      GATA factors occupy a central position between canonical and non-canonical Wnt
      signalling in regulating heart muscle formation.

PMID- 18715947
TI  - Polycomb-dependent Ultrabithorax Hox gene silencing induced by high Ultrabithorax
      levels in Drosophila.
AB  - The Ultrabithorax (Ubx) gene of Drosophila specifies the third thoracic and first
      abdominal segments. Ubx expression is controlled by several mechanisms, including
      negative regulation by its own product. We show here that if Ubx expression
      levels are inappropriately elevated, overriding the auto-regulatory control, a
      permanent repression of Ubx is established. This continuous repression becomes
      independent of the presence of exogenous Ubx and leads to the paradoxical result
      that an excess of Ubx results in a phenotype of Ubx loss. The mechanism of
      permanent repression depends on Polycomb-group genes. Absence of endogenous Ubx
      transcription when Ubx levels are highly elevated probably activates Polycomb
      complexes on a Polycomb response element located in the Ubx major intron. This,
      in turn, brings about permanent repression of Ubx transcription. Similar results
      are obtained with the gene engrailed, showing that this mechanism of permanent
      repression may be a general one for genes with negative auto-regulation when
      levels of expression are transitorily elevated.

PMID- 18715948
TI  - A dual requirement for Iroquois genes during Xenopus kidney development.
AB  - The Iroquois (Irx) genes encode evolutionary conserved homeoproteins. We report
      that Xenopus genes Irx1 and Irx3 are expressed and required during different
      stages of Xenopus pronephros development. They are initially expressed during mid
      neurulation in domains extending over most of the prospective pronephric
      territory. Expression onset takes place after kidney anlage specification, but
      before pronephric organogenesis occurs. Later, during nephron segmentation,
      expression becomes restricted to the intermediate tubule region of the proximal
      distal axis. Loss- and gain-of-function analyses, performed with specific
      morpholinos and inducible wild-type and dominant-negative constructs, reveal a
      dual requirement for Irx1 and Irx3 during pronephros development. During neurula
      stages, these genes maintain the specification of the pronephric territory and
      define its size. This seems to occur, at least in part, through positive
      regulation of Bmp signalling. Subsequently, Irx genes are required for proper
      formation of the intermediate tubule. Finally, we find that retinoic acid
      signalling activates both Irx1 and Irx3 genes in the pronephros.

PMID- 18715949
TI  - Conditional inactivation of Myc impairs development of the exocrine pancreas.
AB  - Recent studies have shown that Wnt/beta-catenin signaling is essential for
      development of the exocrine pancreas, but the role of beta-catenin-dependent
      target genes such as Myc during pancreatic development is not well known. Here,
      we show that tissue-specific deletion of Myc causes a slightly accelerated
      differentiation of pancreatic epithelial cells into endocrine cells and perturbs
      the proliferation of pancreatic progenitors and acinar precursor cells during
      early development, resulting in a severe reduction of the epithelial cell mass of
      pancreatic buds and an extensive acinar hypoplasia. Loss of Myc does not affect
      the expression of the tissue-specific transcription factor PTF1a, which is
      required for the differentiation of acinar cells. In contrast to its role for
      exocrine cell growth, the development of endocrine cell lineages is not
      significantly disturbed. These data suggest that Myc is required for the
      expansion of the exocrine pancreas. Our observations are consistent with the
      findings in beta-catenin-deficient pancreas, suggesting that Wnt/beta-catenin
      signaling affects the proliferation of pancreatic epithelial cells and acinar
      precursors through its target gene Myc.

PMID- 18715950
TI  - Motexafin gadolinium and involved field radiation therapy for intrinsic pontine
      glioma of childhood: a Children's Oncology Group phase I study.
AB  - The purpose of this study was to determine the dose-limiting toxicities, maximum
      tolerated dose, pharmacokinetics, and intratumor and brain distribution of
      motexafin gadolinium (MGd) with involved field radiation therapy in children with
      newly diagnosed intrinsic pontine gliomas. MGd was administered as a 5-min
      intravenous bolus 2-5 h prior to standard radiation. The starting dose was 1.7
      mg/kg. After first establishing that 5 doses/week for 6 weeks was tolerable, the
      dose of MGd was escalated until dose-limiting toxicity was reached. Radiation
      therapy was administered to 54 Gy in 30 once-daily fractions. Forty-four children
      received MGd at doses of 1.7 to 9.2 mg/kg daily prior to radiation therapy for 6
      weeks. The maximum tolerated dose was 4.4 mg/kg. The primary dose-limiting
      toxicities were grade 3 and 4 hypertension and elevations in serum transaminases.
      Median elimination half-life and clearance values were 6.6 h and 25.4 ml/kg/h,
      respectively. The estimated median survival was 313 days (95% confidence
      interval, 248-389 days). The maximum tolerated dose of MGd and the recommended
      phase II dose was 4.4 mg/kg when administered as a daily intravenous bolus in
      conjunction with 6 weeks of involved field radiation therapy for pediatric
      intrinsic pontine gliomas.

PMID- 18715951
TI  - Lithium inhibits invasion of glioma cells; possible involvement of glycogen
      synthase kinase-3.
AB  - Therapies targeting glioma cells that diffusely infiltrate normal brain are
      highly sought after. Our aim was to identify novel approaches to this problem
      using glioma spheroid migration assays. Lithium, a currently approved drug for
      the treatment of bipolar illnesses, has not been previously examined in the
      context of glioma migration. We found that lithium treatment potently blocked
      glioma cell migration in spheroid, wound-healing, and brain slice assays. The
      effects observed were dose dependent and reversible, and worked using every
      glioma cell line tested. In addition, there was little effect on cell viability
      at lithium concentrations that inhibit migration, showing that this is a specific
      effect. Lithium treatment was associated with a marked change in cell morphology,
      with cells retracting the long extensions at their leading edge. Examination of
      known targets of lithium showed that inositol monophosphatase inhibition had no
      effect on glioma migration, whereas inhibition of glycogen synthase kinase-3 (GSK
      3) did. This suggested that the effects of lithium on glioma cell migration could
      possibly be mediated through GSK-3. Specific pharmacologic GSK-3 inhibitors and
      siRNA knockdown of GSK-3alpha or GSK-3beta isoforms both reduced cell motility.
      These data outline previously unidentified pathways and inhibitors that may be
      useful for the development of novel anti-invasive therapeutics for the treatment
      of brain tumors.

PMID- 18715952
TI  - Tumor-growth-promoting cyclooxygenase-2 prostaglandin E2 pathway provides
      medulloblastoma therapeutic targets.
AB  - Prostaglandin E(2) (PGE(2)) has been shown to play important roles in several
      aspects of tumor development and progression. PGE(2) is synthesized from
      arachidonic acid by cyclooxygenases (COX) and prostaglandin E synthases (PGES)
      and mediates its biological activity through binding to the four prostanoid
      receptors EP(1) through EP(4). In this study, we show for the first time that
      medulloblastoma (MB), the most common malignant childhood brain tumor, expresses
      high levels of COX-2, microsomal prostaglandin E synthase-1, and EP(1) through
      EP(4) and secretes PGE(2). PGE(2) and the EP(2) receptor agonist butaprost
      stimulated MB cell proliferation. Treatment of MB cells with COX inhibitors
      suppressed PGE(2) production and induced caspase-dependent apoptosis. Similarly,
      specific COX-2 silencing by small interfering RNA inhibited MB cell growth. EP(1)
      and EP(3) receptor antagonists ONO-8713 and ONO-AE3-240, but not the EP(4)
      antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation,
      indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth.
      Administration of COX inhibitors at clinically achievable nontoxic concentrations
      significantly inhibited growth of established human MB xenografts. Apoptosis was
      increased, proliferation was reduced, and angiogenesis was inhibited in MBs
      treated with COX inhibitors. This study suggests that PGE(2) is important for MB
      growth and that therapies targeting the prostanoid metabolic pathway are
      potentially beneficial and should be tested in clinical settings for treatment of
      children with MB.

PMID- 18715953
TI  - Root and shoot respiration of perennial ryegrass are supplied by the same
      substrate pools: assessment by dynamic 13C labeling and compartmental analysis of
      tracer kinetics.
AB  - The substrate supply system for respiration of the shoot and root of perennial
      ryegrass (Lolium perenne) was characterized in terms of component pools and the
      pools' functional properties: size, half-life, and contribution to respiration of
      the root and shoot. These investigations were performed with perennial ryegrass
      growing in constant conditions with continuous light. Plants were labeled with
      (13)CO(2)/(12)CO(2) for periods ranging from 1 to 600 h, followed by measurements
      of the rates and (13)C/(12)C ratios of CO(2) respired by shoots and roots in the
      dark. Label appearance in roots was delayed by approximately 1 h relative to
      shoots; otherwise, the tracer time course was very similar in both organs.
      Compartmental analysis of respiratory tracer kinetics indicated that, in both
      organs, three pools supplied 95% of all respired carbon (a very slow pool whose
      kinetics could not be characterized provided the remaining 5%). The pools' half
      lives and relative sizes were also nearly identical in shoot and root (half-life
      < 15 min, approximately 3 h, and 33 h). An important role of short-term storage
      in supplying respiration was apparent in both organs: only 43% of respiration was
      supplied by current photosynthate (fixed carbon transferred directly to centers
      of respiration via the two fastest pools). The residence time of carbon in the
      respiratory supply system was practically the same in shoot and root. From this
      and other evidence, we argue that both organs were supplied by the same pools and
      that the residence time was controlled by the shoot via current photosynthate and
      storage deposition/mobilization fluxes.

PMID- 18715954
TI  - Characterization of an autonomously activated plant ADP-glucose
      pyrophosphorylase.
AB  - ADP-glucose pyrophosphorylase (AGPase) catalyzes the rate-limiting step in starch
      biosynthesis in plants and changes in its catalytic and/or allosteric properties
      can lead to increased starch production. Recently, a maize (Zea mays)/potato
      (Solanum tuberosum) small subunit mosaic, MP [Mos(1-198)], containing the first
      198 amino acids of the small subunit of the maize endosperm enzyme and the last
      277 amino acids from the potato tuber enzyme, was expressed with the maize
      endosperm large subunit and was reported to have favorable kinetic and allosteric
      properties. Here, we show that this mosaic, in the absence of activator, performs
      like a wild-type AGPase that is partially activated with 3-phosphoglyceric acid
      (3-PGA). In the presence of 3-PGA, enzyme properties of Mos(1-198)/SH2 are quite
      similar to those of the wild-type maize enzyme. In the absence of 3-PGA, however,
      the mosaic enzyme exhibits greater activity, higher affinity for the substrates,
      and partial inactivation by inorganic phosphate. The Mos(1-198)/SH2 enzyme is
      also more stable to heat inactivation. The different properties of this protein
      were mapped using various mosaics containing smaller portions of the potato small
      subunit. Enhanced heat stability of Mos(1-198) was shown to originate from five
      potato-derived amino acids between 322 and 377. These amino acids were shown
      previously to be important in small subunit/large subunit interactions. These
      five potato-derived amino acids plus other potato-derived amino acids distributed
      throughout the carboxyl-terminal portion of the protein are required for the
      enhanced catalytic and allosteric properties exhibited by Mos(1-198)/SH2.

PMID- 18715955
TI  - The effect of leaf-level spatial variability in photosynthetic capacity on
      biochemical parameter estimates using the Farquhar model: a theoretical analysis.
AB  - Application of the widely used Farquhar model of photosynthesis in interpretation
      of gas exchange data assumes that photosynthetic properties are homogeneous
      throughout the leaf. Previous studies showed that heterogeneity in stomatal
      conductance (g(s)) across a leaf could affect the shape of the measured leaf
      photosynthetic CO(2) uptake rate (A) versus intercellular CO(2) concentration
      (C(i)) response curve and, in turn, estimation of the critical biochemical
      parameters of this model. These are the maximum rates of carboxylation
      (V(c,max)), whole-chain electron transport (J(max)), and triose-P utilization
      (V(TPU)). The effects of spatial variation in V(c,max,) J(max), and V(TPU) on
      estimation of leaf averages of these parameters from A-C(i) curves measured on a
      whole leaf have not been investigated. A mathematical model incorporating defined
      degrees of spatial variability in V(c,max) and J(max) was constructed. One
      hundred and ten theoretical leaves were simulated, each with the same average
      V(c,max) and J(max), but different coefficients of variation of the mean (CV(VJ))
      and varying correlation between V(c,max) and J(max) (Omega). Additionally, the
      interaction of variation in V(c,max) and J(max) with heterogeneity in V(TPU),
      g(s), and light gradients within the leaf was also investigated. Transition from
      V(c,max)- to J(max)-limited photosynthesis in the A-C(i) curve was smooth in the
      most heterogeneous leaves, in contrast to a distinct inflection in the absence of
      heterogeneity. Spatial variability had little effect on the accuracy of
      estimation of V(c,max) and J(max) from A-C(i) curves when the two varied in
      concert (Omega = 1.0), but resulted in underestimation of both parameters when
      they varied independently (up to 12.5% in V(c,max) and 17.7% in J(max) at CV(VJ)
      = 50%; Omega = 0.3). Heterogeneity in V(TPU) also significantly affected
      parameter estimates, but effects of heterogeneity in g(s) or light gradients were
      comparatively small. If V(c,max) and J(max) derived from such heterogeneous
      leaves are used in models to project leaf photosynthesis, actual A is
      overestimated by up to 12% at the transition between V(c,max)- and J(max)-limited
      photosynthesis. This could have implications for both crop production and Earth
      system models, including projections of the effects of atmospheric change.

PMID- 18715956
TI  - slr1923 of Synechocystis sp. PCC6803 is essential for conversion of 3,8
      divinyl(proto)chlorophyll(ide) to 3-monovinyl(proto)chlorophyll(ide).
AB  - The deduced amino acid sequence of an slr1923 gene of Synechocystis sp. PCC6803
      is homologous to archaean F(420)H(2) dehydrogenase, which acts as a soluble
      subcomplex of reduced nicotinamide adenine dinucleotide dehydrogenase complex I.
      In this study, the gene was inactivated and characteristics of the mutant were
      analyzed. The mutant grew slower than the wild type under 100 microE m(-2) s(-1)
      but did not grow under high light intensity (300 microE m(-2) s(-1)). The
      cellular content of chlorophyll was lower in the mutant, and the absorption
      spectrum showed a shift in the absorption peak of the Soret band to a longer
      wavelength by about 10 nm compared with the wild type. It was found, by high
      performance liquid chromatography analysis, that the retention time of
      chlorophyll of the mutant is shorter than that of the wild type and that the peak
      wavelength of the Soret band was also shifted to a longer wavelength by 11 nm.
      Proton nuclear magnetic resonance analysis of the chlorophyll of the mutant
      revealed that the ethyl group of position 8 of ring B is replaced with a vinyl
      group. The spectrum indicates that the chlorophyll of the mutant is not a normal
      (3-vinyl)chlorophyll a but a 3,8-divinylchlorophyll a. These results strongly
      suggest that the Slr1923 protein is essential for the conversion from
      divinylchlorophyll(ide) to normal chlorophyll(ide). We thus designate this gene
      cvrA (a gene indispensable for cyanobacterial vinyl reductase).

PMID- 18715957
TI  - Chloroplast outer envelope protein CHUP1 is essential for chloroplast anchorage
      to the plasma membrane and chloroplast movement.
AB  - Chloroplasts change their intracellular distribution in response to light
      intensity. Previously, we isolated the chloroplast unusual positioning1 (chup1)
      mutant of Arabidopsis (Arabidopsis thaliana). This mutant is defective in normal
      chloroplast relocation movement and shows aggregation of chloroplasts at the
      bottom of palisade mesophyll cells. The isolated gene encodes a protein with an
      actin-binding motif. Here, we used biochemical analyses to determine the
      subcellular localization of full-length CHUP1 on the chloroplast outer envelope.
      A CHUP1-green fluorescent protein (GFP) fusion, which was detected at the
      outermost part of mesophyll cell chloroplasts, complemented the chup1 phenotype,
      but GFP-CHUP1, which was localized mainly in the cytosol, did not. Overexpression
      of the N-terminal hydrophobic region (NtHR) of CHUP1 fused with GFP (NtHR-GFP)
      induced a chup1-like phenotype, indicating a dominant-negative effect on
      chloroplast relocation movement. A similar pattern was found in chloroplast OUTER
      ENVELOPE PROTEIN7 (OEP7)-GFP transformants, and a protein containing OEP7 in
      place of NtHR complemented the mutant phenotype. Physiological analyses of
      transgenic Arabidopsis plants expressing truncated CHUP1 in a chup1 mutant
      background and cytoskeletal inhibitor experiments showed that the coiled-coil
      region of CHUP1 anchors chloroplasts firmly on the plasma membrane, consistent
      with the localization of coiled-coil GFP on the plasma membrane. Thus, CHUP1
      localization on chloroplasts, with the N terminus inserted into the chloroplast
      outer envelope and the C terminus facing the cytosol, is essential for CHUP1
      function, and the coiled-coil region of CHUP1 prevents chloroplast aggregation
      and participates in chloroplast relocation movement.

PMID- 18715958
TI  - Importance of lineage-specific expansion of plant tandem duplicates in the
      adaptive response to environmental stimuli.
AB  - Plants have substantially higher gene duplication rates compared with most other
      eukaryotes. These plant gene duplicates are mostly derived from whole genome
      and/or tandem duplications. Earlier studies have shown that a large number of
      duplicate genes are retained over a long evolutionary time, and there is a clear
      functional bias in retention. However, the influence of duplication mechanism,
      particularly tandem duplication, on duplicate retention has not been thoroughly
      investigated. We have defined orthologous groups (OGs) between Arabidopsis
      (Arabidopsis thaliana) and three other land plants to examine the functional bias
      of retained duplicate genes during vascular plant evolution. Based on analysis of
      Gene Ontology categories, it is clear that genes in OGs that expanded via tandem
      duplication tend to be involved in responses to environmental stimuli, while
      those that expanded via nontandem mechanisms tend to have intracellular
      regulatory roles. Using Arabidopsis stress expression data, we further
      demonstrated that tandem duplicates in expanded OGs are significantly enriched in
      genes that are up-regulated by biotic stress conditions. In addition, tandem
      duplication of genes in an OG tends to be highly asymmetric. That is, expansion
      of OGs with tandem genes in one organismal lineage tends to be coupled with
      losses in the other. This is consistent with the notion that these tandem genes
      have experienced lineage-specific selection. In contrast, OGs with genes
      duplicated via nontandem mechanisms tend to experience convergent expansion, in
      which similar numbers of genes are gained in parallel. Our study demonstrates
      that the expansion of gene families and the retention of duplicates in plants
      exhibit substantial functional biases that are strongly influenced by the
      mechanism of duplication. In particular, genes involved in stress responses have
      an elevated probability of retention in a single-lineage fashion following tandem
      duplication, suggesting that these tandem duplicates are likely important for
      adaptive evolution to rapidly changing environments.

PMID- 18715959
TI  - Cytokinin stimulates chloroplast transcription in detached barley leaves.
AB  - Chloroplasts are among the main targets of cytokinin action in the plant cell. We
      report here on the activation of transcription by cytokinin as detected by run-on
      assays with chloroplasts isolated from apical parts of first leaves detached from
      9-d-old barley (Hordeum vulgare) seedlings and incubated for 3 h on a 2.2 x 10(
      5) m solution of benzyladenine (BA). Northern-blot analysis also detected a BA
      induced increase in the accumulation of chloroplast mRNAs. A prerequisite for BA
      activation of chloroplast transcription was preincubation of leaves for 24 h on
      water in the light, resulting in a decreased chloroplast transcription and a
      drastic accumulation of abscisic acid. Cytokinin enhanced the transcription of
      several chloroplast genes above the initial level measured before BA treatment,
      and in the case of rrn16 and petD even before preincubation. Cytokinin effects on
      basal (youngest), middle, and apical (oldest) segments of primary leaves detached
      from plants of different ages revealed an age dependence of chloroplast gene
      response to BA. BA-induced stimulation of transcription of rrn16, rrn23, rps4,
      rps16, rbcL, atpB, and ndhC required light during the period of preincubation and
      was further enhanced by light during the incubation on BA, whereas activation of
      transcription of trnEY, rps14, rpl16, matK, petD, and petLG depended on light
      during both periods. Our data reveal positive and differential effects of
      cytokinin on the transcription of chloroplast genes that were dependent on light
      and on the age (developmental stage) of cells and leaves.

PMID- 18715960
TI  - Reconfiguration of the achene and receptacle metabolic networks during strawberry
      fruit development.
AB  - The anatomy of strawberry (Fragaria x ananassa) fruit, in which the achene is
      found on the outer part of the fruit, makes it an excellent species for studying
      the regulation of fruit development. It can provide a model for the cross talk
      between primary and secondary metabolism, whose role is of pivotal importance in
      the process. By combining gas chromatography-mass spectrometry and liquid
      chromatography-mass spectrometry with the aim of addressing the metabolic
      regulation underlying fruit seed development, we simultaneously analyzed the
      composition of primary and secondary metabolites, separately, in achene and
      receptacle during fruit ripening of strawberry cultivar Herut. The results from
      these analyses suggest that changes in primary and secondary metabolism reflect
      organ and developmental specificities. For instance, the receptacle was
      characterized by increases in sugars and their direct derivatives, while the
      achene was characterized by a major decrease in the levels of carbon- and
      nitrogen-rich compounds, with the exception of storage-related metabolites (e.g.
      raffinose). Furthermore, the receptacle, and to a lesser extent the achene,
      exhibited dynamic fluctuations in the levels and nature of secondary metabolites
      across the ripening process. In the receptacle, proanthocyanidins and flavonol
      derivatives characterized mainly early developmental stages, while anthocyanins
      were abundant in the mature red stage; in the achene, ellagitannin and flavonoids
      were abundant during early and late development, respectively. Correlation-based
      network analysis suggested that metabolism is substantially coordinated during
      early development in either organ. Nonetheless, a higher degree of connectivity
      within and between metabolic pathways was measured in the achenes. The data are
      discussed within the context of current models both of the interaction of primary
      and secondary metabolism and of the metabolic interaction between the different
      plant organs.

PMID- 18715961
TI  - Discrete and essential roles of the multiple domains of Arabidopsis FHY3 in
      mediating phytochrome A signal transduction.
AB  - Phytochrome A is the primary photoreceptor for mediating various far-red light
      induced responses in higher plants. We recently showed that Arabidopsis
      (Arabidopsis thaliana) FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and FAR-RED-IMPAIRED
      RESPONSE1 (FAR1), a pair of homologous proteins sharing significant sequence
      homology to Mutator-like transposases, act as novel transcription factors
      essential for activating the expression of FHY1 and FHL (for FHY1-like), whose
      products are required for light-induced phytochrome A nuclear accumulation and
      subsequent light responses. FHY3, FAR1, and Mutator-like transposases also share
      a similar domain structure, including an N-terminal C2H2 zinc finger domain, a
      central putative core transposase domain, and a C-terminal SWIM motif (named
      after SWI2/SNF and MuDR transposases). In this study, we performed a promoter
      swapping analysis of FHY3 and FAR1. Our results suggest that the partially
      overlapping functions of FHY3 and FAR1 entail divergence of their promoter
      activities and protein subfunctionalization. To gain a better understanding of
      the molecular mode of FHY3 function, we performed a structure-function analysis,
      using site-directed mutagenesis and transgenic approaches. We show that the
      conserved N-terminal C2H2 zinc finger domain is essential for direct DNA binding
      and biological function of FHY3 in mediating light signaling, whereas the central
      core transposase domain and C-terminal SWIM domain are essential for the
      transcriptional regulatory activity of FHY3 and its homodimerization or
      heterodimerization with FAR1. Furthermore, the ability to form homodimers or
      heterodimers largely correlates with the transcriptional regulatory activity of
      FHY3 in plant cells. Together, our results reveal discrete roles of the multiple
      domains of FHY3 and provide functional support for the proposition that FHY3 and
      FAR1 represent transcription factors derived from a Mutator-like transposase(s).

PMID- 18715962
TI  - Rh-PIP2;1, a rose aquaporin gene, is involved in ethylene-regulated petal
      expansion.
AB  - Aquaporins are water channel proteins that facilitate the passage of water
      through biological membranes and play a crucial role in plant growth. We showed
      that ethylene treatment significantly reduced petal size, inhibited expansion of
      petal abaxial subepidermal cells, and decreased petal water content in rose (Rosa
      hybrida 'Samantha'). Here, we report the isolation of a plasma membrane aquaporin
      (PIP) gene, Rh-PIP2;1, and characterized its potential role in ethylene-inhibited
      petal expansion. Rh-PIP2;1 is mainly localized on the plasma membrane and belongs
      to the class 2 subfamily of PIP proteins. We show that Rh-PIP2;1 is an active
      water channel. The transcripts of Rh-PIP2;1 are highly abundant in petal
      epidermal cells, especially in the abaxial subepidermal cells. The expression of
      Rh-PIP2;1 is highly correlated with petal expansion and tightly down-regulated by
      ethylene. Furthermore, we demonstrate that in Rh-PIP2;1-silenced flowers, petal
      expansion was greatly inhibited and anatomical features of the petals were
      similar to those of ethylene-treated flowers. We argue that Rh-PIP2;1 plays an
      important role in petal cell expansion and that ethylene inhibits petal expansion
      of roses at least partially by suppressing Rh-PIP2;1 expression.

PMID- 18715963
TI  - Prevalence of chronic kidney disease in Kinshasa: results of a pilot study from
      the Democratic Republic of Congo.
AB  - BACKGROUND: The burden of chronic kidney disease (CKD) in sub-Saharan Africa is
      unknown. The aim of this study was to investigate the prevalence and the risk
      factors associated with CKD in Kinshasa, the capital of the Democratic Republic
      of Congo (DRC). METHODS: In a cross-sectional study, 503 adult residents in 10 of
      the 35 health zones of Kinshasa were studied in a randomly selected sample.
      Glomerular filtration rate was estimated using the simplified Modification of
      Diet in Renal Disease Study equation (eGFR) and compared with the Cockcroft-Gault
      equation for creatinine clearance. The associations between health
      characteristics, indicators of kidney damage (proteinuria) and kidney function
      (<60 ml/min/1.73 m(2)) were examined. RESULTS: The prevalence of all stages of
      CKD according to K/DOQI guidelines was 12.4% [95% confidence interval (CI), 11.0
      15.1%]. By stage, 2% had stage 1 (proteinuria with normal eGFR), 2.4% had stage 2
      (proteinuria with an eGFR of 60-89 ml/min/1.73 m(2)), 7.8% had stage 3 (eGFR, 30
      59 ml/min/1.73 m(2)) and 0.2% had stage 5 (eGFR < 15 ml/min/1.73 m(2)).
      Hypertension and age were independently associated with CKD stage 3. The
      prevalences of major non-communicable diseases considered in this study were
      27.6% (95% CI, 25.7-31.3%) for hypertension, 11.7% (95% CI, 10.3-14.4%) for
      diabetes mellitus and 14.9% (95% CI, 13.3-17.9%) for obesity. Hypertension was
      also independently associated with proteinuria. CONCLUSION: More than 10% of the
      Kinshasa population exhibits signs of CKD, which is affecting adults in their
      productive years. Risk factors for CKD, including hypertension, diabetes and
      obesity, are increasing. These alarming data must guide current and future
      healthcare policies to meet the challenge raised by CKD in this city and
      hopefully in the whole country.

PMID- 18715964
TI  - Increased acid excretion in kidney stone formers with essential hypertension.
AB  - BACKGROUND: Although several studies have reported that kidney stone disease and
      hypertension are associated, the link between the two conditions has not been
      identified. This study investigated urinary excretion of different solutes,
      particularly citrate and acids, in kidney stone formers and examined their
      association with high blood pressure. METHODS: The retrospective study included
      234 consecutive subjects, aged 47.0 +/- 15.6, attending our metabolic clinic
      after episodes of kidney stones. Essential hypertension was present in 82
      patients (35.0%). A difference in the urinary excretion of some of the
      investigated components was found between subjects with normal blood pressure and
      those with hypertension. RESULTS: The results showed that hypertensive subjects
      were older and had a higher body mass index (BMI) and serum uric acid. They had a
      significantly lower urinary pH (5.6 +/- 0.4 versus 6.0 +/- 0.5) and citrate (2.55
      +/- 1.36 versus 2.83 +/- 1.65 mmol/24 h), higher titratable acid (38.8 +/- 19.0
      versus 26.8 +/- 15.0 mEq/24 h) and ammonium (41.6 +/- 17.6 versus 34.2 +/-12.4
      mmol/24 h). Logistic regression analysis with the presence of hypertension as the
      dependent variable produced a model with the following predictors: age (P <
      0.0001), BMI (P = 0.026), titratable acid (P = 0.025) and low urinary citrate
      level (P = 0.033). Urinary acid excretion increased with the stage of
      hypertension. No difference was found in the urinary excretion of other solutes.
      CONCLUSIONS: These findings suggest that essential hypertension and acid
      excretion are linked in stone formers.

PMID- 18715965
TI  - Beginning again from the end.

PMID- 18715966
TI  - Preparing for palliative medicine; evaluation of an education programme for
      fourth year medical undergraduates.
AB  - Prompted by directives from the GMC, 'care of the dying' is identified as 'core
      curricula' for undergraduate medical education. However, there are many technical
      and interpersonal challenges faced in learning the practice of palliative
      medicine. Accordingly, the design and delivery of education programmes need to be
      both carefully considered and evaluated. Using Bandura's Social Cognitive Theory
      as a driver, appropriate methodology for evaluating a novel education programme
      in palliative medicine was drafted. A pre- and post-survey of an education
      programme and palliative care placement for fourth year medical undergraduate
      students from Liverpool University (n = 216) was completed using a composite
      questionnaire containing; i) Self-efficacy in Palliative Care Scale (SEPC) and
      ii) Thanatophobia Scale. Both scales have shown reliability and validity within
      the sample population. Additionally, a randomly selected Focus Group was
      conducted to provide qualitative information on the students' experience. A total
      of 139 pre- and post-questionnaires (64%) were completed. Analysis identified
      significant improvements in perceived efficacy (SEPC Communication t = -16.41, P
      < 0.001; SEPC Patient Management t = -22.31, P < 0.001; SEPC Multidisciplinary
      Teamwork t = -15.56, P < 0.001). Significant improvements in thanatophobia were
      also recorded (z = -7.51, P < 0.001) although some interesting anomalies were
      noted. This study demonstrates that considered and appropriately structured
      clinical education has been shown to significantly improve students' belief in
      their ability to practice palliative medicine and to improve their attitude
      towards care. In accordance with the study's theoretical driver, it is reasonable
      to propose that the engaged active learning will have a positive effect on the
      future care of dying patients.

PMID- 18715967
TI  - Non-pharmacological interventions for breathlessness management in patients with
      lung cancer: a systematic review.
AB  - The aim is to review the published scientific literature for studies evaluating
      non-pharmacological interventions for breathlessness management in patients with
      lung cancer. The following selection criteria were used to systematically search
      the literature: studies were to be published research or systematic reviews; they
      were to be published in English and from 1990 to 2007; the targeted populations
      were adult patients with dyspnoea/breathlessness associated with lung cancer; and
      the study reported on the outcomes from use of non-pharmacological strategies for
      breathlessness. This review retrieved five studies that met all inclusion
      criteria. All the studies reported the benefits of non-pharmacological
      interventions in improving breathlessness regardless of differences in clinical
      contexts, components of programmes and methods for delivery. Analysis of the
      available evidence suggests that tailored instructions delivered by nurses with
      sufficient training and supervision may have some benefits over other delivery
      approaches. Based on the results, non-pharmacological interventions are
      recommended as effective adjunctive strategies in managing breathlessness for
      patients with lung cancer. In order to refine such interventions, future research
      should seek to explore the core components of such approaches that are critical
      to achieving optimal outcomes, the contexts in which the interventions are most
      effective, and to evaluate the relative benefits of different methods for
      delivering such interventions.

PMID- 18715968
TI  - Population-based study of dying in hospital in six European countries.
AB  - This study examined the proportion of deaths taking place in hospitals in six
      European countries in relation to demographic, epidemiologic and healthcare
      factors. Retrospective analyses were performed on a database integrating death
      certificate data of all deaths in 2002 in Sweden and 2003 in Belgium, England,
      Scotland, the Netherlands and Wales (N = 891,780). Data were linked with regional
      healthcare statistics. Of all deaths, from 33.9% (the Netherlands) to 62.8%
      (Wales) occurred in hospital. Large country differences in hospital deaths were
      partly explained by the availability of care home and hospital beds. Differences
      between countries were strikingly large in older patients and cancer patients.
      Older patients had a higher probability of dying in hospital in Sweden, Scotland,
      England and Wales than in Flanders and, in particular, in the Netherlands. Cancer
      patients often died in hospitals in Sweden but less frequently so in the
      Netherlands and England. Country differences in the proportion of patients dying
      in hospital are only partly the result of differences in health care provision,
      and are in particular larger for certain patient categories, suggesting country
      specific end-of-life practices in these categories. These findings can contribute
      to rational public health policies aimed at reducing hospital deaths.

PMID- 18715969
TI  - Development and validation of a prognostic scale for use in patients with
      advanced cancer.
AB  - The aim of this study was to develop a new prognostic indicator to help predict
      survival in advanced cancer patients more accurately. Data on 329 patients
      obtained from a multi-centre study in London were analysed. A multifactorial Cox
      regression model was applied and validated using bootstrapping techniques.
      Predictive scores were calculated and used to produce a new prognostic index. The
      value of the index in predicting 14-day survival was then assessed. Four
      variables were found to be associated with worse survival: primary lung cancer,
      secondary liver cancer, raised C-Reactive protein and poor performance status
      (ECOG 4). Survival curves showed that patients designated as 'high' risk by the
      resulting index had significantly shorter survival than those designated as 'low'
      risk. A high score on the newly derived prognostic index is associated with
      poorer survival, but its clinical utility is limited by the relatively low
      predictive probability of the score.

PMID- 18715970
TI  - Continued study of the psychometric properties of the McGill quality of life
      questionnaire.
AB  - The McGill Quality of Life Questionnaire (MQOL) is a widely used tool that has
      been specifically developed to measure the quality of life of patients facing a
      life-threatening illness. Preferably, a self-report instrument has an equal
      number of items worded positively and negatively. However, all the psychological
      scales of the MQOL are worded so that a high score is negative, whereas the
      existential scales are worded so that a high score is positive. The goal of this
      study was to investigate the influence of MQOL item formatting on patient
      responses. In order to do so, a modified version of the questionnaire was
      distributed to and completed by 205 patients in two oncology clinics. The
      modified version had an equal amount of items worded in a positive direction and
      negative direction in each of the domains. Results of this study were found to be
      different from those of other studies: the loading of the items was partly based
      on scale direction. These changes support the idea that the MQOL formatting has
      some impact on patient responses. However, factors were also determined by
      content. Given that MQOL has been widely used and the original formatting
      provides conceptually clearer subscales, we suggest maintaining the original
      format, keeping in mind the effect of formatting when interpreting scores.

PMID- 18715971
TI  - Validation of a consciousness level scale for palliative care.
AB  - The main objective of this study is to validate a Consciousness Scale for
      palliative care. The scale was named Consciousness Scale for palliative care
      (CSPC). The validation had two phases: 1) face validity--the scale was assessed
      by seven healthcare professionals, both doctors and nurses, experienced in
      palliative care; 2) reliability and construct validity--performed by four
      investigators, two nurses and two doctors. The construct validation was performed
      by comparing the CSPC with a Visual Analogue Scale (VAS) of 100 mm, anchored in
      the terms 'awake' and 'unarousable', and then with the Glasgow Coma Scale (GCS).
      In this study, all four observers completed 44 periods of observation relative to
      38 patients resulting in a total of 176 observations. In the phase of face
      validation, there were no discrepancies in relation to the issue: the scale
      provides measures for measurement; the scale can be useful to clinical practice;
      the scale can improve communication among professionals and the scale is easy to
      use. As a measure of internal consistency, Cronbach's alpha was found to be very
      high (0.99). The inter-rater reliability was also very high with an intraclass
      correlation coefficient of 0.99 (P < 0.001). The correlation of the CSPC to the
      VAS was 0.94 (P < 0.001) and the CSPC to the GCS was -0.82 (P < 0.001). The CSPC
      can be a very useful tool for assessing consciousness in palliative care
      patients. It is very ease to use, not time consuming and can be used with minimal
      training. Communication between professionals can be improved in the clinical
      setting and in the research environment.

PMID- 18715972
TI  - Palliative care education in Swiss undergraduate medical curricula: a case of too
      little, too early.
AB  - Palliative medicine education is an important strategy in ensuring that the needs
      of terminally ill patients are met. A review was conducted in 2007 of the
      undergraduate curricula of all five of Switzerland's medical schools to identify
      their palliative care-related content and characteristics. The average number of
      mandatory hours of palliative care education is 10.2 h (median 8 h; range 0-27
      h), significantly short of the 40 h recommended by the European Palliative Care
      Association's Education Expert Group. The median time allocated to designated
      palliative care blocks is 3 h (range 0-8 h). Most of the education occurs before
      the clinical years, and there are no mandatory clinical rotations. Three schools
      offer optional clinical rotations but these are poorly attended (<10% of
      students). Although a number of domains are covered, ethics-related content
      predominates; 21 of a total of 51 obligatory hours (41%). Communication related
      to palliative care is largely limited to 'breaking bad news'. In two of the
      schools, the teaching is done primarily by palliative care physicians and nurses
      (70% or more of the teaching). In the others, it is done mostly by educators in
      other clinical specialties and ethics (approximately 90% of the teaching). These
      findings show significant deficiencies.

PMID- 18715973
TI  - Implementation and impact of the Gold Standards Framework in community palliative
      care: a qualitative study of three primary care trusts.
AB  - The Gold Standards Framework (GSF) has been widely adopted within UK general
      practices, yet there is little understanding of its impact on the provision of
      community palliative care services. This study presents data on the anticipation
      and adoption of the GSF within three Primary Care Trusts in North West England.
      Forty-seven interviews were conducted with generalist and specialist palliative
      and primary care professionals. Important aspects of the GSF identified were the
      patient register, communication and out-of-hours protocols. Positive benefits to
      professionals included improved communication between professionals and
      appropriate anticipatory prescribing. Negative aspects included increased nursing
      workload and the possibility of fewer or later visits for patients. Many
      respondents believed that the GSF needed local champions to be sustainable. Slow
      or incomplete adoption was reported. The GSF was recognised as important because
      it facilitated changes to previously difficult aspects of work between
      professionals, but few respondents reported direct benefits to patient care.

PMID- 18715974
TI  - Making the most of routine data in palliative care research--a case study
      analysis of linked hospital and mortality data on cancer and heart failure
      patients in Scotland and Oxford.
AB  - The research base of palliative care is growing rapidly, but despite
      methodological advances, some of the practical challenges of working with people
      at the end of life will persist. This means that analysis of routine data is
      arguably more important in studying palliative care than it is in other aspects
      of health services research. End-of-life researchers have been using the high
      quality linked data from cancer registries for many years. This paper explores
      the value of a less well-known resource for palliative care research: linked
      mortality and hospital activity data. Two case studies are presented using
      information from Scotland (population 5.1 million) and the former Oxford region
      of England (population 2.5 million). The advantages and limitations of linked
      hospital and mortality data for research and service planning in palliative care
      are drawn out through analyses investigating hospital bed utilisation by people
      with cancer and heart failure and the influence of social deprivation on the use
      of hospital services in the last year of life. The use of such data deserves a
      higher profile.

PMID- 18715975
TI  - Benefits and pitfalls of pooling datasets from comparable observational studies:
      combining US and Dutch nursing home studies.
AB  - Different research groups sometimes carry out comparable studies. Combining the
      data can make it possible to address additional research questions, particularly
      for small observational studies such as those frequently seen in palliative care
      research. We present a systematic approach to pool individual subject data from
      observational studies that addresses differences in research design, illustrating
      the approach with two prospective observational studies on treatment and outcomes
      of lower respiratory tract infection in US and Dutch nursing home residents.
      Benefits of pooling individual subject data include enhanced statistical power,
      the ability to compare outcomes and validate models across sites or settings, and
      opportunities to develop new measures. In our pooled dataset, we were able to
      evaluate treatments and end-of-life decisions for comparable patients across
      settings, which suggested opportunities to improve care. In addition, greater
      variation in participants and treatments in the combined dataset allowed for
      subgroup analyses and interaction hypotheses, but required more complex analytic
      methods. Pitfalls included the large amount of time required for equating study
      procedures and variables and the need for additional funding.

PMID- 18715976
TI  - Clinical and financial analysis of an acute palliative care unit in an
      oncological department.
AB  - The aim of this article is to describe the clinical activity and medical
      intervention of an acute model of palliative care unit (APC), as well as the
      reimbursement procedures and economic viability. A sample of 504 patients
      admitted at an APC in 1 year was surveyed. Indications for admission, pain and
      symptom intensity, analgesic treatments, procedures, instrumental examinations
      and modalities of discharge were recorded. For each patient, tariff for
      reimbursement was calculated according to the existent disease related grouping
      (DRG) system. The mean age was 62 years, and 246 patients were males. The mean
      hospital stay was 5.4 days. Pain control was the most frequent indication for
      admission. All patients had laboratory tests and several instrumental
      examinations. Almost all patients were prescribed one or more opioids at
      significant doses, and different routes of administration, as well as medication
      as needed. 59 patients received blood cell transfusions and 34 interventional
      procedures. Only 40 patients died in the unit, 11 of them being sedated at the
      end of life. Treatment efficacy was considered optimal and mild in 264 and 226
      patients respectively. A mean of 3019 euros for admission was reimbursed by the
      Health Care System. APCs are of paramount importance within an oncological
      department, as they provide effective and intensive treatments during the entire
      course of disease, providing a simultaneous and integrated approach. Our findings
      also suggest both a cost and quality incentive for oncological departments to
      develop APC.

PMID- 18715977
TI  - How does the environment impact on the quality of life of advanced cancer
      patients? A qualitative study with implications for ward design.
AB  - It is well recognized that the ward environment has an effect on patients'
      quality of life and may, therefore, impact on the quality of end of life care.
      The body of evidence that informs ward design policy recommends single-bedded
      rooms on grounds of reduced infection risk, noise and versatility. Considering
      the majority of anticipated patient deaths occurring in hospitals, the quality of
      life aspects of ward design should also be considered. The aim of this study is
      to explore the views of patients with advanced cancer on the effect the ward
      environment has on their overall well-being. Semi-structured interviews exploring
      the experiences of 12 inpatients at a regional cancer centre were recorded and
      transcribed verbatim. Transcripts were analysed for emerging themes until
      theoretical saturation. Four major themes emerged: staff behaviours, the
      immediate environment, single vs. multi-bedded rooms and contact with the outside
      environment. The attitude, competence and helpfulness of the staff creates the
      atmosphere of the ward regardless of layout, furnishings, equipment and decor.
      The majority of the patients in this study expressed a strong preference for a
      multi-bedded room when they were well enough to interact and a single cubicle
      when they were very ill or dying, which opposes the current advice for building
      new hospitals with all single rooms. Although the current policy recommends the
      use of single-bedded rooms, this study suggests the need for a mix of multi
      bedded wards and single rooms with respect to the impact of the environment on
      patient quality of life.

PMID- 18715978
TI  - Outpatient management of malignant pleural effusion with chronic pleural
      catheter.

PMID- 18715979
TI  - The role of epidural phenol in cancer patients at the end of life.

PMID- 18715980
TI  - SPINKL, a Kazal-type serine protease inhibitor-like protein purified from mouse
      seminal vesicle fluid, is able to inhibit sperm capacitation.
AB  - We report a secreted serine protease inhibitor Kazal-type-like (SPINKL) protein.
      The SPINKL protein was purified from mouse seminal vesicle secretions through a
      series of steps, including ion-exchange chromatography on a diethylaminoethyl
      Sephacel column, gel filtration on a Sephadex G-75 column, and ion-exchange HPLC
      on a Q strong anion exchange column. Further analysis identified several SPINKL
      proteins with various N-linked carbohydrates. The SPINKL protein has six
      conserved cysteine residues that are nearly identical to those of members of the
      SPINK protein family. It was noted that the SPINKL protein showed no inhibitory
      activities against common serine proteases such as trypsin, chymotrypsin,
      subtilisin, or elastase. Spinkl mRNA and SPINKL proteins were found to be
      primarily expressed in seminal vesicles. Immunohistochemistry revealed that the
      SPINKL protein occurred in the luminal fluid and mucosal epithelium of the
      seminal vesicles and was regulated by testosterone. The SPINKL protein was able
      to bind onto sperm and enhance sperm motility. Also, it was able to suppress BSA
      stimulated sperm capacitation and block sperm-oocyte interactions in vitro,
      suggesting that SPINKL may be a decapacitation factor.

PMID- 18715981
TI  - Melatonin-enhanced hyperactivation of hamster sperm.
AB  - The effects of melatonin on reproductive function were examined using hamster
      spermatozoa. When 1 pM to 1 microM melatonin was added to the mTALP medium,
      hyperactivation was significantly enhanced. Antagonists and agonists of the
      melatonin receptor (i.e., MT1 and MT2) were added to the medium. Luzindole, an
      MT1 and MT2 competitive antagonist, significantly inhibited melatonin-induced
      hyperactivation, whereas the MT2-specific antagonists, 4-phenyl-2
      propionamidotetralin and N-pentanoyl-2-benzyltryptamine, had no effect. Moreover,
      hyperactivation was significantly enhanced when non-specific agonists, such as 6
      chloromelatonin and 2-iodomelatonin, were added to the medium. 8-Methoxy-2
      propionamidotetralin, which is a strong MT2 agonist and a weak MT1 agonist,
      significantly increased hyperactivation, although the effect was weak. Therefore,
      it is likely that melatonin enhances sperm hyperactivation via the MT1 receptor.

PMID- 18715982
TI  - The absence of corpus luteum formation alters the endocrine profile and affects
      follicular development during the first follicular wave in cattle.
AB  - We previously established a bovine experimental model showing that the corpus
      luteum (CL) does not appear following aspiration of the preovulatory follicle
      before the onset of LH surge. Using this model, the present study aimed to
      determine the profile of follicular development and the endocrinological
      environment in the absence of CL with variable nadir circulating progesterone
      (P(4)) concentrations during the oestrous cycle in cattle. Luteolysis was induced
      in heifers and cows and they were assigned either to have the dominant follicle
      aspirated (CL-absent) or ovulation induced (CL-present). Ultrasound scanning to
      observe the diameter of each follicle and blood collection was performed from the
      day of follicular aspiration or ovulation and continued for 6 days. The CL-absent
      cattle maintained nadir circulating P(4) throughout the experimental period and
      showed a similar diameter between the largest and second largest follicle,
      resulting in co-dominant follicles. Oestradiol (E(2)) concentrations were greater
      in the CL-absent cows than in the CL-present cows at day -1, day 1 and day 2 from
      follicular deviation. The CL-absent cows had a higher basal concentration, area
      under the curve (AUC), pulse amplitude and pulse frequency of LH than the CL
      present cows. After follicular deviation, the CL-absent cows showed a greater
      basal concentration, AUC and pulse amplitude of growth hormone (GH) than the CL
      present cows. These results suggest that the absence of CL accompanying nadir
      circulating P(4) induces an enhancement of LH pulses, which involves the growth
      of the co-dominant follicles. Our results also suggest that circulating levels of
      P(4) and E(2) affect pulsatile GH secretion in cattle.

PMID- 18715983
TI  - Danish study links cancer survival to income and education.

PMID- 18715988
TI  - South Africa withdraws TB drugs because of quality concerns.

PMID- 18715989
TI  - Platelets undergo phosphorylation of Syk at Y525/526 and Y352 in response to
      pathophysiological shear stress.
AB  - Atherosclerotic plaques can lead to partial vascular occlusions that produce
      abnormally high levels of arterial wall shear stress. Such pathophysiological
      shear stress can promote shear-induced platelet aggregation (SIPA), which has
      been linked to acute myocardial infarction, unstable angina, and stroke. This
      study investigated the role of the tyrosine kinase Syk in shear-induced human
      platelet signaling. The extent of Syk tyrosine phosphorylation induced by
      pathophysiological levels of shear stress (100 dyn/cm(2)) was significantly
      greater than that resulting from physiological shear stress (10 dyn/cm(2)). With
      the use of phospho-Syk specific antibodies, these data are the first to show that
      key regulatory sites of Syk at tyrosines 525/526 (Y525/526) and tyrosine 352
      (Y352) were phosphorylated in response to pathophysiological shear stress.
      Increased phosphorylation at both sites was attenuated by pharmacological
      inhibition of Syk using two different Syk inhibitors, piceatannol and 3-(1-methyl
      1H-indol-3-yl-methylene)-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide (OXSI-2), and
      by inhibition of upstream Src-family kinases (SFKs). Shear-induced response at
      the Syk 525/526 site was ADP dependent but not contingent on glycoprotein (GP)
      IIb-IIIa ligation or the generation of thromboxane (Tx) A(2). Pretreatment with
      Syk inhibitors not only reduced SIPA and Syk phosphorylation in isolated
      platelets, but also diminished, up to 50%, the platelet-mediated thrombus
      formation when whole blood was perfused over type-III collagen. In summary, this
      study demonstrated that Syk is a key molecule in both SIPA and thrombus formation
      under flow. Pharmacological regulation of Syk may prove efficacious in treating
      occlusive vascular disease.

PMID- 18715990
TI  - What regulates Na+/Ca2+ exchange? Focus on "Sodium-dependent inactivation of
      sodium/calcium exchange in transfected Chinese hamster ovary cells".

PMID- 18715991
TI  - Academic etiquette for the nephrologist.
AB  - Academic etiquette is an underexplored and underemphasized topic. Yet, a
      collegial atmosphere is essential to accomplish the missions of an academic
      medical center. Appropriate social, personal, and cultural behaviors are not only
      desirable, but they are also necessary to practice and emulate. As faculty in an
      academic center, one may want to share these thoughts with peers, students, and
      other healthcare providers. As a trainee, one may want dedicated lectures on this
      topic and to observe the behaviors modeled by mentors. This article attempts to
      outline principles of appropriate etiquette in the academic workplace. These
      include issues of loyalty, collegiality, and collaboration in daily activities
      from research to clinical care. Approaching personal interactions with grace and
      integrity can be an essential tool in the pursuit of academic excellence and
      success.

PMID- 18715992
TI  - Structure of a signal transduction regulator, RACK1, from Arabidopsis thaliana.
AB  - The receptor for activated C-kinase 1 (RACK1) is a highly conserved WD40 repeat
      scaffold protein found in a wide range of eukaryotic species from Chlamydymonas
      to plants and humans. In tissues of higher mammals, RACK1 is ubiquitously
      expressed and has been implicated in diverse signaling pathways involving
      neuropathology, cellular stress, protein translation, and developmental
      processes. RACK1 has established itself as a scaffold protein through physical
      interaction with a myriad of signaling proteins ranging from kinases,
      phosphatases, ion channels, membrane receptors, G proteins, IP3 receptor, and
      with widely conserved structural proteins associated with the ribosome. In the
      plant Arabidopsis thaliana, RACK1A is implicated in diverse developmental and
      environmental stress pathways. Despite the functional conservation of RACK1
      mediated protein-protein interaction-regulated signaling modes, the structural
      basis of such interactions is largely unknown. Here we present the first crystal
      structure of a RACK1 protein, RACK1 isoform A from Arabidopsis thaliana, at 2.4 A
      resolution, as a C-terminal fusion of the maltose binding protein. The structure
      implicates highly conserved surface residues that could play critical roles in
      protein-protein interactions and reveals the surface location of proposed post
      transcriptionally modified residues. The availability of this structure provides
      a structural basis for dissecting RACK1-mediated cellular signaling mechanisms in
      both plants and animals.

PMID- 18715994
TI  - Epigenetics, development, and the kidney.
AB  - How cells partition the genome into active and inactive genes and how that
      information is established and propagated during embryonic development are
      fundamental to maintaining the normal differentiated state. The molecular
      mechanisms of epigenetic action and cellular memory are increasingly amenable to
      study primarily as a result of the rapid progress in the area of chromatin
      biology. Methylation of DNA and modification of histones are critical epigenetic
      marks that establish active and silent chromatin domains. During development of
      the kidney, DNA-binding factors such as Pax2/8, which are essential for the
      intermediate mesoderm and the renal epithelial lineage, could provide the locus
      and tissue specificity for histone methylation and chromatin remodeling and thus
      establish a kidney-specific fate. The role of epigenetic modifications in
      development and disease is under intense investigation and has already affected
      our view of cancer and aging.

PMID- 18715993
TI  - Ischemia-induced exocytosis of Weibel-Palade bodies mobilizes stem cells.
AB  - Recruitment of various stem and progenitor cells is crucial for the regeneration
      of an injured organ. Levels of uric acid, one of the prototypical "alarm
      signals," surge after ischemia-reperfusion injury. Exogenous uric acid rapidly
      mobilizes endothelial progenitor cells and hematopoietic stem cells and protects
      the kidney from ischemia. The relatively fast responses to uric acid suggest that
      preformed second messengers may be released from a storage pool. Here, it is
      reported that monosodium urate (MSU) results in exocytosis of Weibel-Palade
      bodies in vitro and in vivo, leading to the release of IL-8, von Willebrand
      factor, and angiopoietin 2 in the culture medium or circulation. Confocal and
      immunoelectron microscopy confirmed depletion of von Willebrand factor in MSU
      treated aortic endothelial cells. Angiopoietin 2 alone induced exocytosis of
      Weibel-Palade bodies, mobilized hematopoietic stem cells and depleted splenic
      endothelial progenitor cells, partially reproducing the actions of MSU. In
      addition, pretreatment with angiopoietin 2 protected the kidneys from an ischemic
      insult, suggesting that the previously reported renoprotection conferred by MSU
      likely results from exocytosis of Weibel-Palade bodies. Furthermore, experiments
      with toll-like receptor 4 (TLR-4)-and TLR-2-deficient mice demonstrated that uric
      acid-induced exocytosis of Weibel-Palade bodies is mediated by TLR-4 and that
      uric acid-induced release of IL-8 requires both TLR-2 and TLR-4. In summary,
      these results suggest that exocytosis of Weibel-Palade bodies links postischemic
      repair with inflammation and mobilization of stem cells.

PMID- 18715995
TI  - Endothelial progenitor cells are cellular hubs essential for neoangiogenesis of
      certain aggressive adenocarcinomas and metastatic transition but not adenomas.

PMID- 18715996
TI  - Heparan sulfate regulates ephrin-A3/EphA receptor signaling.
AB  - Increasing evidence indicates that many signaling pathways involve not only
      ligands and receptors but also various types of coreceptors and matrix components
      as additional layers of regulation. Signaling by Eph receptors and their ephrin
      ligands plays a key role in a variety of biological processes, such as axon
      guidance and topographic map formation, synaptic plasticity, angiogenesis, and
      cancer. Little is known about whether the ephrin-Eph receptor signaling system is
      subject to such additional layers of regulation. Here, we show that ephrin-A3
      binds to heparan sulfate, and that the presence of cell surface heparan sulfate
      is required for the full biological activity of ephrin-A3. Among the ephrins
      tested, including ephrin-A1, -A2, -A5, -B1, and -B2, only ephrin-A3 binds heparin
      or heparan sulfate. Ephrin-A3-dependent EphA receptor activation is reduced in
      mutant cells that are defective in heparan sulfate synthesis, in wild-type cells
      from which cell surface heparan sulfate has been removed, and in the hippocampus
      of conditional knockout mice defective in heparan sulfate synthesis. Ephrin-A3
      dependent cell rounding is impaired in CHO cells lacking heparan sulfate, and
      cortical neurons lacking heparan sulfate exhibit impaired growth cone collapse.
      In contrast, cell rounding and growth cone collapse in response to ephrin-A5,
      which does not bind heparan sulfate, are not affected by the absence of heparan
      sulfate. These results show that heparan sulfate modulates ephrin/Eph signaling
      and suggest a physiological role for heparan sulfate proteoglycans in the
      regulation of ephrin-A3-dependent biological processes.

PMID- 18715997
TI  - Does cohesin regulate developmental gene expression in Drosophila?

PMID- 18715998
TI  - Confusing cortical columns.

PMID- 18715999
TI  - Calmodulin dynamically regulates the trafficking of the metabotropic glutamate
      receptor mGluR5.
AB  - Metabotropic glutamate receptors (mGluRs) 1-8 are G protein-coupled receptors
      (GPCRs) that modulate excitatory neurotransmission, neurotransmitter release, and
      synaptic plasticity. PKC regulates many aspects of mGluR function, including
      protein-protein interactions, Ca(2+) signaling, and receptor desensitization.
      However, the mechanisms by which PKC regulates mGluR function are poorly
      understood. We have now identified calmodulin (CaM) as a dynamic regulator of
      mGluR5 trafficking. We show that the major PKC phosphorylation site on the
      intracellular C terminus of mGluR5 is serine 901 (S901), and phosphorylation of
      this residue is up-regulated in response to both receptor and PKC activation. In
      addition, S901 phosphorylation inhibits mGluR5 binding to CaM, decreasing mGluR5
      surface expression. Furthermore, blocking PKC phosphorylation of mGluR5 on S901
      dramatically affects mGluR5 signaling by prolonging Ca(2+) oscillations. Thus,
      our data demonstrate that mGluR5 activation triggers phosphorylation of S901,
      thereby directly linking PKC phosphorylation, CaM binding, receptor trafficking,
      and downstream signaling.

PMID- 18716000
TI  - Structural basis of Clostridium perfringens toxin complex formation.
AB  - The virulent properties of the common human and livestock pathogen Clostridium
      perfringens are attributable to a formidable battery of toxins. Among these are a
      number of large and highly modular carbohydrate-active enzymes, including the mu
      toxin and sialidases, whose catalytic properties are consistent with degradation
      of the mucosal layer of the human gut, glycosaminoglycans, and other cellular
      glycans found throughout the body. The conservation of noncatalytic ancillary
      modules among these enzymes suggests they make significant contributions to the
      overall functionality of the toxins. Here, we describe the structural basis of an
      ultra-tight interaction (K(a) = 1.44 x 10(11) M(-1)) between the X82 and dockerin
      modules, which are found throughout numerous C. perfringens carbohydrate-active
      enzymes. Extensive hydrogen-bonding and van der Waals contacts between the X82
      and dockerin modules give rise to the observed high affinity. The mu-toxin
      dockerin module in this complex is positioned approximately 180 degrees relative
      to the orientation of the dockerin modules on the cohesin module surface within
      cellulolytic complexes. These observations represent a unique property of these
      clostridial toxins whereby they can associate into large, noncovalent multitoxin
      complexes that allow potentiation of the activities of the individual toxins by
      combining complementary toxin specificities.

PMID- 18716003
TI  - Evaluation of a single preoperative dose of pregabalin for attenuation of
      postoperative pain after laparoscopic cholecystectomy.
AB  - BACKGROUND: Postoperative pain is the dominating complaint and the primary reason
      for prolonged convalescence after laparoscopic cholecystectomy. We have evaluated
      the efficacy of a single preoperative dose of pregabalin for attenuating
      postoperative pain and fentanyl consumption after laparoscopic cholecystectomy.
      METHODS: Sixty adults (16-60 yr), ASA physical status I and II, of either sex
      undergoing elective laparoscopic cholecystectomy were included in this
      prospective, randomized placebo controlled, double-blind study. Subjects were
      divided into two groups of 30 each to receive either a matching placebo or
      pregabalin 150 mg, administered orally 1 h before surgery. Postoperative pain
      (static and dynamic) was assessed by a 100 mm visual analogue scale, where 0, no
      pain; 100, worst imaginable pain. Subjects received patient-controlled i.v.
      fentanyl analgesia during the postoperative period. Results were analysed by
      Student's t-test, chi(2) test, Mann-Whitney U-test, and Fisher's exact test.
      RESULTS: Postoperative pain (static and dynamic) and postoperative patient
      controlled fentanyl consumption were reduced in the pregabalin group compared
      with the placebo group (P<0.05). Side-effects were similar in both groups.
      CONCLUSIONS: A single preoperative oral dose of pregabalin 150 mg is an effective
      method for reducing postoperative pain and fentanyl consumption in patients
      undergoing laparoscopic cholecystectomy.

PMID- 18716002
TI  - Interferon-alpha initiates type 1 diabetes in nonobese diabetic mice.
AB  - With the goal of identifying changes in gene expression in CD4(+) T cells during
      the development of diabetes in the nonobese diabetic (NOD) mouse, we used DNA
      microarrays to analyze gene expression in CD4(+) T cells from the pancreatic
      draining lymph nodes of NOD/BDC 2.5 T cell receptor transgenic and WT NOD mice at
      different ages. At 4 and 6 weeks of age, we found up-regulation of a number of
      genes that are known to be induced by IFN-alpha. IFN-alpha levels and IFN-alpha
      producing plasmacytoid dendritic cells were increased in the PLNs of 3- to 4-week
      old NOD mice. Moreover, blockade of IFN-alpha receptor 1 in NOD mice by a
      neutralizing antibody at 2-3 weeks of age significantly delayed the onset and
      decreased the incidence of type 1 diabetes, increased the relative number of
      immature dendritic cells in the PLNs, and enhanced the ability of spleen CD4(+) T
      cells to produce IL-4 and IL-10. These findings demonstrate that IFN-alpha in the
      PLNs is an essential initiator in the pathogenesis of type 1 diabetes in NOD
      mice.

PMID- 18716004
TI  - Intrathecal lidocaine elevates prostaglandin E2 levels in cerebrospinal fluid: a
      microdialysis study in freely moving rats.
AB  - BACKGROUND: In this study, we have investigated whether intrathecal (i.t.)
      lidocaine administration is accompanied with changes of cerebrospinal fluid (CSF)
      prostaglandin E(2) (PGE(2)) levels. METHODS: Rats were anaesthetized for i.t.
      implantation of a triple-lumen spinal loop dialysis catheter. CSF changes in
      PGE(2) after i.t. injection of saline, 400, or 1000 microg of lidocaine were
      measured. The impact of i.t. pretreatment with 5 microg MK801 (N-methyl-D
      aspartate glutamate antagonist) or 10 microg SC76309A (COX-2 inhibitor) was also
      investigated. CSF dialysates for measurement of PGE(2) were collected for 4 h.
      During the whole procedure, motor and sensory blocks were evaluated. A separate
      group receiving i.t. lidocaine 400 microg (without dialysate sampling) was
      assessed for mechanical (Von Frey) and radiant heat pain. RESULTS: PGE(2) levels
      increased to 400% of baseline and remained elevated for 90-120 min after i.t.
      lidocaine at both doses. Pretreatment with SC76309A and MK801 attenuated this
      increase. A 40 min period of enhanced pain response was observed after Von Frey
      filament stimulation during and after sensory and motor block recovery.
      CONCLUSIONS: I.T. lidocaine (400 or 1000 microg) increases PGE(2) levels in the
      CSF for 90-120 min along with a transient period of mechanical hyperalgesia after
      sensory and motor block recovery.

PMID- 18716005
TI  - Glucocorticoid response elements and 11 beta-hydroxysteroid dehydrogenases in the
      regulation of endothelial nitric oxide synthase expression.
AB  - AIMS: Hypertensive and other effects of excess glucocorticoids might be in part
      mediated by the suppression of endothelial nitric oxide synthase (eNOS)
      expression. We studied the transcriptional and biochemical mechanisms that
      mediate or modulate the suppression of eNOS expression by glucocorticoids.
      METHODS AND RESULTS: We found that a mere three-fold increase in the
      concentration of the natural glucocorticoid cortisol (from 30 to 100 nmol/L)
      significantly decreased the expression level of eNOS in human endothelial cells.
      Deletion analysis of the eNOS promoter indicated that the segment within -119 bp
      upstream from the transcription start site was significantly involved in the
      effect of cortisol. Site-directed mutagenesis and chromatin immunoprecipitation
      analyses demonstrated the presence of a suppressive glucocorticoid response
      element (GRE) at -111 to -105 bp. 11 beta-hydroxysteroid dehydrogenases (11 beta
      HSD) catalyse the interconversion of active and inactive glucocorticoids. The
      suppression of 11 beta-HSD2 using small interfering RNA markedly exacerbated the
      inhibition of eNOS by cortisol. The suppression of 11 beta-HSD1 abolished the
      inhibition of eNOS expression by cortisol. CONCLUSION: We identified the first
      GRE in the eNOS promoter region and demonstrated that endogenous 11 beta-HSD1 and
      11 beta-HSD2 play significant and distinct roles in modulating the effect of
      glucocorticoids on eNOS expression.

PMID- 18716006
TI  - Patterns and prognostic implications of low high-density lipoprotein levels in
      patients with non-ST-segment elevation acute coronary syndromes.
AB  - AIMS: The patterns and prognostic significance of low high-density lipoprotein
      (HDL) cholesterol levels have not been well characterized. We sought to determine
      the prevalence and prognostic significance of low HDL cholesterol levels in
      patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS).
      METHODS AND RESULTS: We evaluated HDL levels among NSTE ACS patients [ischaemic
      ECG (electrocardiogram) changes and/or positive cardiac markers] from the CRUSADE
      [Can Rapid Stratification of Unstable Angina Patients Suppress Adverse Outcomes
      with Early Implementation of the ACC(American College of Cardiology)/AHA(American
      Heart Association) Guidelines] initiative treated at 555 US hospitals from
      January 2001 through June 2006. Clinical and angiographic characteristics,
      treatments, and in-hospital outcomes were analysed by categories of HDL levels
      measured during hospitalization. Among 93 263 NSTE ACS patients with HDL
      measurements, 16 854 (18.1%) had very low HDL levels (10-29 mg/dL), 32 185
      (34.5%) had low HDL levels (30-39 mg/dL), 35 875 (38.5%) had normal HDL levels
      (40-59 mg/dL), and 8349 (9.0%) had high HDL levels (60-100 mg/dL). Patients with
      very low HDL levels were younger, more often male, and more commonly obese and
      diabetic. Patients with very low HDL levels had the greatest risk of multi-vessel
      coronary disease on angiography and in-hospital mortality compared with patients
      with normal and high HDL levels. CONCLUSION: Almost one-fifth of patients with
      NSTE ACS have very low HDL levels--a finding that adds incrementally to a greater
      burden of atherosclerosis and a higher risk of mortality. Consequently,
      strategies for mitigating the adverse prognosis associated with very low HDL
      levels warrant further exploration in patients with ACS.

PMID- 18716007
TI  - Selection of antigens and development of prototype tests for point-of-care
      leprosy diagnosis.
AB  - Leprosy can be a devastating chronic infection that causes nerve function
      impairment and associated disfigurement. Despite the recent reduction in the
      number of registered worldwide leprosy cases as a result of the widespread use of
      multidrug therapy, the number of new cases detected each year remains relatively
      stable. The diagnosis of leprosy is currently based on the appearance of clinical
      signs and requires expert clinical, as well as labor-intensive and time-consuming
      laboratory or histological, evaluation. For the purpose of developing an
      effective, simple, rapid, and low-cost diagnostic alternative, we have analyzed
      the serologic antibody response to identify Mycobacterium leprae proteins that
      are recognized by leprosy patients. More than 100 recombinant antigens were
      analyzed in a protein array format to select those with discriminatory properties
      for leprosy diagnosis. As expected, multibacillary leprosy patients recognized
      more antigens with stronger antibody responses than paucibacillary leprosy
      patients. Our data indicate, however, that multibacillary patients can be
      distinguished from paucibacillary patients, and both of these groups can be
      segregated from endemic control groups. We went on to confirm the diagnostic
      properties of antigens ML0405 and ML2331 and the LID-1 fusion construct of these
      two proteins by enzyme-linked immunosorbent assay. We then demonstrated the
      performance of these antigens in rapid test formats with a goal of developing a
      point-of-care diagnostic test. A serological diagnostic test capable of
      identifying and allowing treatment of leprosy could reduce transmission, prevent
      functional disabilities and stigmatizing deformities, and facilitate leprosy
      eradication.

PMID- 18716008
TI  - Detection of an antigenic group 2 coronavirus in an adult alpaca with enteritis.
AB  - Antigenic group 2 coronavirus was detected in a fecal sample of an adult alpaca
      by reverse transcription-PCR. The presence of alpaca coronavirus (ApCoV) in the
      small intestine was demonstrated by immune histochemistry with an
      antinucleocapsid monoclonal antibody that reacts with group 2 coronaviruses.
      Other common causes of diarrhea in adult camelids were not detected. We conclude
      that nutritional stress may have predisposed the alpaca to severe ApCoV
      infection.

PMID- 18716009
TI  - Impact of clinical variables on Borrelia burgdorferi-specific antibody
      seropositivity in acute-phase sera from patients in North America with culture
      confirmed early Lyme disease.
AB  - Erythema migrans, the most common manifestation of Lyme disease, has been
      associated with highly variable rates of seropositivity for antibodies to
      Borrelia burgdorferi. Differences in the sensitivities of serologic assays for
      the detection of these antibodies, however, may not be the only or even the
      primary explanation for this observation. We investigated the impacts of four
      clinical variables on seropositivity--the duration of erythema migrans, the
      presence of single versus multiple skin lesions, and the gender and age of the
      patient. In this analysis, three different serologic tests were performed on
      acute-phase sera from 175 untreated patients with culture-confirmed erythema
      migrans: the C6 single-peptide enzyme-linked immunosorbent assay (ELISA), a
      commercially available ELISA in which a whole-cell sonicate of B. burgdorferi was
      the antigen, and a two-tier procedure. Irrespective of the serologic test
      performed, the results showed that seropositivity rates increased with the
      duration of the erythema migrans for patients with single lesions (P < 0.001) but
      not for those with multiple skin lesions. The variability in seropositivity rates
      was greatest for the two-tier testing strategy, with a >6-fold-higher rate of
      seropositivity among patients with a single lesion of 22- to 30-day duration than
      among those whose skin lesion was of 1- to 7-day duration (85.7 versus 14.1%; P <
      0.001). Rates of seropositivity by each of the testing methods were also
      significantly higher for patients with multiple skin lesions than for those with
      single lesions (P < 0.001). In contrast, seropositivity rates were not affected
      by either the gender or the age of the patient. Thus, in patients with erythema
      migrans, certain clinical variables such as the duration and number of skin
      lesions had a profound impact on seropositivity rates, irrespective of the
      serologic assay performed.

PMID- 18716010
TI  - Life saving early and immediate aspirin: too little too late.

PMID- 18716001
TI  - Extreme diversity of tropical parasitoid wasps exposed by iterative integration
      of natural history, DNA barcoding, morphology, and collections.
AB  - We DNA barcoded 2,597 parasitoid wasps belonging to 6 microgastrine braconid
      genera reared from parapatric tropical dry forest, cloud forest, and rain forest
      in Area de Conservacion Guanacaste (ACG) in northwestern Costa Rica and combined
      these data with records of caterpillar hosts and morphological analyses. We asked
      whether barcoding and morphology discover the same provisional species and
      whether the biological entities revealed by our analysis are congruent with wasp
      host specificity. Morphological analysis revealed 171 provisional species, but
      barcoding exposed an additional 142 provisional species; 95% of the total is
      likely to be undescribed. These 313 provisional species are extraordinarily host
      specific; more than 90% attack only 1 or 2 species of caterpillars out of more
      than 3,500 species sampled. The most extreme case of overlooked diversity is the
      morphospecies Apanteles leucostigmus. This minute black wasp with a distinctive
      white wing stigma was thought to parasitize 32 species of ACG hesperiid
      caterpillars, but barcoding revealed 36 provisional species, each attacking one
      or a very few closely related species of caterpillars. When host records and/or
      within-ACG distributions suggested that DNA barcoding had missed a species-pair,
      or when provisional species were separated only by slight differences in their
      barcodes, we examined nuclear sequences to test hypotheses of presumptive species
      boundaries and to further probe host specificity. Our iterative process of
      combining morphological analysis, ecology, and DNA barcoding and reiteratively
      using specimens maintained in permanent collections has resulted in a much more
      fine-scaled understanding of parasitoid diversity and host specificity than any
      one of these elements could have produced on its own.

PMID- 18716011
TI  - See one, do one, then what? Faculty development in postgraduate medical
      education.
AB  - Interest in the development of medical educators working in the postgraduate
      sector is running high. Driven by three interlinked trends--the
      professionalization of medical education, increasing accountability, and the
      pursuit of educational excellence--there is a growing need for high quality and
      sustained faculty development programmes across the network of education
      providers. Postgraduate medical education has a number of unique features that
      set it apart from undergraduate medicine, to which faculty development programmes
      need to cater. The key issue for the future will be how to engage the service in
      the business of education. Widespread cultural change is required and this will
      require effective and sympathetic leadership from postgraduate training
      institutions, hospitals and health authorities.

PMID- 18716012
TI  - The inter-operator variability in measuring waist circumference and its potential
      impact on the diagnosis of the metabolic syndrome.
AB  - OBJECTIVE: The International Diabetes Federation (IDF) has proposed ethnicity
      specific cut-off values for waist circumference, as an essential criterion for
      the diagnosis of the metabolic syndrome (MetS). However, before introducing waist
      circumference measurement as part of the clinical examination, or an obligatory
      criterion for MetS, it is important to ensure that the measurement is reliable
      and reproducible. STUDY DESIGN: The inter- and intra-operator variability in
      measuring waist circumference was assessed in a preliminary study of 10 health
      professionals and the inter-operator variability in clinical practice was
      assessed in a study of 102 patients. Repeated measures analysis of variance
      (ANOVA) was used to assess the significance of the inter- and intra-operator
      variability. RESULTS: Intra-operator variability was not found to be significant
      in the preliminary study (F = 0.15, p = 0.764). However, the inter-operator
      variability was significant in both studies (preliminary: F = 4.16, p<0.001,
      clinical practice study: F = 14.06, p<0.001). In clinical practice, this could
      lead to disagreement among operators regarding the presence of central obesity in
      9% of the patients. After giving written instructions on how to measure waist
      circumference, the coefficient of variation was not significantly altered (p =
      0.202) but the inter-operator variability lost significance (F = 2.34, p = 0.11),
      suggesting a reduction in systematic error. CONCLUSIONS: Measuring waist
      circumference is subject to significant inter-operator variability and could
      potentially lead to misclassifying patients as having the MetS, or not. Better
      training of health professionals on how to measure waist circumference properly
      is needed in order to ensure that patients are not misclassified and that
      international comparisons of the prevalence of the MetS are reliable.

PMID- 18716013
TI  - New drug targets for pulmonary hypertension: Rho GTPases in pulmonary vascular
      remodelling.
AB  - Rho GTPases, key regulators of actin dynamics, play a major role in vascular
      processes such as endothelial permeability, cell motility, angiogenesis, nitric
      oxide production, smooth muscle contractility, cell proliferation and
      differentiation. In the lung, Rho GTPases control pulmonary vascular tone and
      remodelling. Their basal activity is important in fetal lung development and
      vascular adaptation to changes in oxygen levels, but their continuous activation
      in neonatal or adult lung leads to the development of pulmonary hypertension
      (PH), a condition characterised by excessive remodelling and hyperconstriction of
      pulmonary arteries. This review, based on recent molecular, cellular and animal
      studies, focuses on the current understanding of Rho GTPases signalling in
      pulmonary vascular physiology and pathophysiology. It also discusses the existing
      and prospective treatments targeting Rho GTPases in the management of PH.

PMID- 18716014
TI  - Approach to critical illness polyneuropathy and myopathy.
AB  - A newly acquired neuromuscular cause of weakness has been found in 25-85% of
      critically ill patients. Three distinct entities have been identified: (1)
      critical illness polyneuropathy (CIP); (2) acute myopathy of intensive care
      (itself with three subtypes); and (3) a syndrome with features of both 1 and 2
      (called critical illness myopathy and/or neuropathy or CRIMYNE). CIP is primarily
      a distal axonopathy involving both sensory and motor nerves. Electroneurography
      and electromyography (ENG-EMG) is the gold standard for diagnosis. CIM is a
      proximal as well as distal muscle weakness affecting both types of muscle fibres.
      It is associated with high use of non-depolarising muscle blockers and
      corticosteroids. Avoidance of systemic inflammatory response syndrome (SIRS) is
      the most effective way to reduce the likelihood of developing CIP or CIM. Outcome
      is variable and depends largely on the underlying illness. Detailed history,
      careful physical examination, review of medication chart and analysis of initial
      investigations provides invaluable clues towards the diagnosis.

PMID- 18716015
TI  - Haemorrhagic transformation in acute ischaemic stroke following thrombolysis
      therapy: classification, pathogenesis and risk factors.
AB  - Haemorrhagic transformation of cerebral infarction is a common and potentially
      serious occurrence following acute ischaemic stroke. Though often a "natural"
      evolution, particularly in acute embolic stroke, haemorrhagic transformation is a
      prime concern with the use of thrombolytic therapy for acute ischaemic stroke.
      The severity of haemorrhage may range from a few petechiae to a large haematoma
      with space occupying effect. The pathogenesis of haemorrhagic transformation is
      not well established, though ischaemia and reperfusion have been proposed to
      cause disruption of the blood-brain barrier leading to extravasation of blood. At
      the molecular level, free radicals and proteolotic enzymes (metalloproteinases)
      may cause tissue injury. Studies have identified a number of clinical,
      radiological, and biochemical parameters that may serve as potential predictors
      of increased risk for haemorrhagic transformation. The knowledge of these factors
      may help in improving patient selection for thrombolytic therapy.

PMID- 18716016
TI  - Endothelial function and inflammation in coronary artery disease.
AB  - Evidence supports the central role of endothelium and inflammation in all phases
      of the atherosclerotic process. Clinical studies have shown their prognostic
      potential for the development of ischaemic events and for adverse outcome after
      acute coronary syndromes. Reduction in inflammatory levels and improving
      endothelial function by traditional and novel treatment strategies were
      associated with a proportional reduction in cardiovascular events. However,
      randomised controlled trials are required to explore further whether drugs
      targeting the inflammatory process and endothelial function will constitute a
      reasonable adjunctive treatment for patients with coronary artery disease.

PMID- 18716017
TI  - Epstein-Barr virus and Burkitt lymphoma.
AB  - Burkitt lymphoma (BL) is an aggressive B-cell malignancy with endemic, sporadic
      and immunodeficiency-associated variants. It has been known for many years that
      the fundamental transforming event in BL is the translocation of the MYC gene,
      and the events that bring about this translocation and those that allow cells to
      survive with the constitutive expression of MYC have been the subject of intense
      investigation. Epstein-Barr virus (EBV) infection, malaria, immunodeficiency and
      spontaneous, somatic mutation can all contribute to the origin and maintenance of
      this cancer and their mechanisms are the subject of this review.

PMID- 18716019
TI  - What to do ... When the treatment does not work: polymyositis.

PMID- 18716018
TI  - Recommendations on diagnostic strategies for chronic inflammatory demyelinating
      polyradiculoneuropathy.
AB  - BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is
      an immune mediated treatable peripheral neuropathy, the diagnosis of which is
      straightforward in more than half of cases. Numerous sets of electrophysiological
      criteria have been published. However, in some cases, electrophysiological data
      are not sufficient and patients that may benefit from treatment escape accurate
      diagnosis. OBJECTIVE: To describe a step by step diagnostic procedure for
      neurologists facing a peripheral neuropathy of undetermined cause, to help make
      an accurate diagnosis of CIDP. METHODS: A group of French experts was
      established, neurologists and neurophysiologists being recruited on the basis of
      personal experience with patients suffering from CIDP and also on publications in
      the field. A full literature review was conducted on the topic of diagnostic
      criteria and procedures for the diagnosis of CIDP, and meetings were scheduled to
      reach a consensus on the best diagnostic workup in different clinical situations.
      RESULTS: Six meetings were conducted and a consensus was reached, based on the
      available literature and experience in the management of such patients.
      Discussions resulted in defining five clinical situations in which a diagnosis of
      CIDP may be considered, and procedures were detailed in each case, including the
      location of nerve biopsy and use of non-conventional electrophysiological testing
      and imaging procedures. CONCLUSION: The guidelines in the diagnostic procedure
      reported here result from a consensus of French experts in the field of
      peripheral neuropathy and allow a diagnosis of CIDP to be made in the most
      frequently encountered situations. These recommendations may be of value for
      physicians as they rely on the rational use of available techniques in typical
      clinical situations.

PMID- 18716020
TI  - Multidisciplinary rehabilitation for adults with multiple sclerosis.

PMID- 18716021
TI  - Lung cancer mimicking left atrial mass.
AB  - Cardiac involvement in lung cancer is found in up to 25% of autopsy cases.
      However, despite the considerable mortality and morbidity associated with cardiac
      metastasis, antemortem diagnosis is unusual. A rare case of lung cancer
      presenting as a left atrial mass is reported.

PMID- 18716022
TI  - Late reactivation of thyroid associated ophthalmopathy causing optic neuropathy.
AB  - We describe a case of thyroid associated ophthalmopathy complicated by optic
      neuropathy presenting 18 years after the diagnosis of dysthyroidism, due to late
      reactivation of a previously stable ophthalmopathy.

PMID- 18716023
TI  - Cocaine-induced spinal cord infarction.

PMID- 18716025
TI  - Functional and structural basis of the nuclear localization signal in the ZIC3
      zinc finger domain.
AB  - Disruptions in ZIC3 cause heterotaxy, a congenital anomaly of the left-right
      axis. ZIC3 encodes a nuclear protein with a zinc finger (ZF) domain that contains
      five tandem C2H2 ZF motifs. Missense mutations in the first ZF motif (ZF1) result
      in defective nuclear localization, which may underlie the pathogenesis of
      heterotaxy. Here we revealed the structural and functional basis of the nuclear
      localization signal (NLS) of ZIC3 and investigated its relationship to the defect
      caused by ZF1 mutation. The ZIC3 NLS was located in the ZF2 and ZF3 regions,
      rather than ZF1. Several basic residues interspersed throughout these regions
      were responsible for the nuclear localization, but R320, K337 and R350 were
      particularly important. NMR structure analysis revealed that ZF1-4 had a similar
      structure to GLI ZF, and the basic side chains of the NLS clustered together in
      two regions on the protein surface, similar to classical bipartite NLSs. Among
      the residues for the ZF1 mutations, C253 and H286 were positioned for the metal
      chelation, whereas W255 was positioned in the hydrophobic core formed by ZF1 and
      ZF2. Tryptophan 255 was a highly conserved inter-finger connector and formed part
      of a structural motif (tandem CXW-C-H-H) that is shared with GLI, Glis and some
      fungal ZF proteins. Furthermore, we found that knockdown of Karyopherin
      alpha1/alpha6 impaired ZIC3 nuclear localization, and physical interactions
      between the NLS and the nuclear import adapter proteins were disturbed by
      mutations in the NLS but not by W255G. These results indicate that ZIC3 is
      imported into the cell nucleus by the Karyopherin (Importin) system and that the
      impaired nuclear localization by the ZF1 mutation is not due to a direct
      influence on the NLS.

PMID- 18716026
TI  - HDL: bridging past and present with a look at the future.
AB  - Clinical and epidemiological studies have shown that HDLs, a class of plasma
      lipoproteins, heterogeneous in size and density, have an atheroprotective role
      attributed, for years, to their capacity to promote the efflux of cholesterol
      from activated cholesterol-loaded arterial macrophages. Recent studies, however,
      have recognized that the physical heterogeneity of HDLs is associated with
      multiple functions that involve both the protein and the lipid components of
      these particles. ApoA-I, quantitatively the major protein constituent, has an
      amphipathic structure suited for transport of lipids. It readily interacts with
      the ATP-binding cassette transporter ABCA1, the SR-B1 scavenger receptor;
      activates the enzyme lecithin-cholesterol acyl transferase (LCAT), which is
      critical for HDL maturation. It also has antioxidant and antiinflammatory
      properties, along with the HDL-associated enzymes paraoxonase, platelet
      activating factor acetylhydrolase (PAF), and glutathione peroxidase. Regarding
      the lipid moiety, an atheroprotective role has been recognized for
      lysosphingolipids, particularly sphingosine-1-phosphate (S1P). All of these
      atheroprotective functions are lost in the post-translational dependent
      dysfunctional plasma HDLs of subjects with systemic inflammation, coronary heart
      disease, diabetes, and chronic renal disease. The emerging notion that particle
      quality has more predictive power than quantity has stimulated further
      exploration of the HDL proteome, already revealing unsuspected pro- or
      antiatherogenic proteins/peptides associated with HDL.

PMID- 18716027
TI  - Increased blood pressure in mice lacking cytochrome P450 2J5.
AB  - The cytochrome P450 (CYP) enzymes participate in a wide range of biochemical
      functions, including metabolism of arachidonic acid and steroid hormones. Mouse
      CYP2J5 is abundant in the kidney where its products, the cis-epoxyeicosatrienoic
      acids (EETs), modulate sodium transport and vascular tone. To define the
      physiological role of CYP2J5 in the kidney, knockout mice were generated using a
      conventional gene targeting approach. Cyp2j5 (-/-) mice develop normally and
      exhibit no overt renal pathology. While renal EET biosynthesis was apparently
      unaffected by the absence of CYP2J5, deficiency of this CYP in female mice was
      associated with increased blood pressure, enhanced proximal tubular transport
      rates, and exaggerated afferent arteriolar responses to angiotensin II and
      endothelin I. Interestingly, plasma 17beta-estradiol levels were reduced in
      female Cyp2j5 (-/-) mice and estrogen replacement restored blood pressure and
      vascular responsiveness to normal levels. There was no evidence of enhanced
      estrogen metabolism, or altered expression or activities of steroidogenic enzymes
      in female Cyp2j5 (-/-) mice, but their plasma levels of luteinizing hormone and
      follicle stimulating hormone were inappropriately low. Together, our findings
      illustrate a sex-specific role for CYP2J5 in regulation of blood pressure,
      proximal tubular transport, and afferent arteriolar responsiveness via an
      estrogen-dependent mechanism.

PMID- 18716029
TI  - Identification and characterization of a new cognitive enhancer based on
      inhibition of insulin-regulated aminopeptidase.
AB  - Approximately one-quarter of people over the age of 65 are estimated to suffer
      some form of cognitive impairment, underscoring the need for effective cognitive
      enhancing agents. Insulin-regulated aminopeptidase (IRAP) is potentially an
      innovative target for the development of cognitive enhancers, as its peptide
      inhibitors exhibit memory-enhancing effects in both normal and memory-impaired
      rodents. Using a homology model of the catalytic domain of IRAP and virtual
      screening, we have identified a class of nonpeptide, small-molecule inhibitors of
      IRAP. Structure-based computational development of an initial "hit" resulted in
      the identification of two divergent families of compounds. Subsequent medicinal
      chemistry performed on the highest affinity compound produced inhibitors with
      nanomolar affinities (K(i) 20-700 nM) for IRAP. In vivo efficacy of one of these
      inhibitors was demonstrated in rats with an acute dose (1 nmol in 1 microl)
      administered into the lateral ventricles, improving performance in both spatial
      working and recognition memory paradigms. We have identified a family of specific
      IRAP inhibitors that is biologically active which will be useful both in
      understanding the physiological role of IRAP and potentially in the development
      of clinically useful cognitive enhancers. Notably, this study also provides
      unequivocal proof of principal that inhibition of IRAP results in memory
      enhancement.

PMID- 18716028
TI  - MicroRNA-377 is up-regulated and can lead to increased fibronectin production in
      diabetic nephropathy.
AB  - Intrinsic glomerular cells in a diabetic milieu have transcriptional activation
      of genes that influence the development of diabetic nephropathy. The cellular
      repertoire of microRNAs can regulate translation of these expressed genes into
      proteins. Fibronectin is a key matrix protein accumulated in excess in diabetic
      nephropathy. Here, we exposed cultured human and mouse mesangial cells to high
      glucose and transforming growth factor-beta to simulate the diabetic milieu. In
      these conditions in vitro, as well as in mouse diabetic nephropathy models in
      vivo, microRNA-377 was consistently up-regulated relative to controls. Through a
      combination of computational and biological approaches, we identified relevant
      miR-377 target genes. Although fibronectin was induced by miR-377, it was not a
      direct target of miR-377. However, miR-377 led to reduced expressions of p21
      activated kinase and superoxide dismutase, which enhanced fibronectin protein
      production. Thus, overexpression of miR-377 in diabetic nephropathy indirectly
      leads to increased fibronectin protein production; as such, miR-377 can have a
      critical role in the pathophysiology of this prevalent human disease.

PMID- 18716030
TI  - A promising cancer gene therapy agent based on the matrix protein of vesicular
      stomatitis virus.
AB  - The matrix (M) protein of vesicular stomatitis virus (VSV) plays a key role in
      inducing cell apoptosis during infection. To investigate whether M protein
      mediated apoptosis could be used in cancer therapy, its cDNA was amplified and
      cloned into eukaryotic expression vector pcDNA3.1(+). The recombinant plasmid or
      the control empty plasmid pcDNA3.1(+) was mixed with cationic liposome and
      introduced into various tumor cell lines in vitro, including lung cancer cell
      LLC, A549, colon cancer cell CT26 and fibrosarcoma cell MethA. Our data showed
      that the M protein induced remarkable apoptosis of cancer cells in vitro compared
      with controls. Fifty micrograms of plasmid in a complex with 250 microg cationic
      liposome was injected intratumorally into mice bearing LLC or MethA tumor model
      every 3 days for 6 times. It was found that the tumors treated with M protein
      plasmid grew much more slowly, and the survival of the mice was significantly
      prolonged compared with the mice treated with the control plasmid. In MethA
      fibrosarcoma, the tumors treated with M protein plasmid were even completely
      regressed, and the mice acquired longtime protection against the same tumor cell
      in rechallenge experiments. Both apoptotic cells and CD8(+) T cells were widely
      distributed in M protein plasmid-treated tumor tissue. Activated cytotoxic T
      lymphocytes (CTLs) were further detected by means of (51)Cr release assay in the
      spleen of the treated mice. These results showed that M protein of VSV can act as
      both apoptosis inducer and immune response initiator, which may account for its
      extraordinary antitumor effect and warrant its further development in cancer gene
      therapy.

PMID- 18716031
TI  - Post-transcriptional regulation of mouse mu opioid receptor (MOR1) via its 3'
      untranslated region: a role for microRNA23b.
AB  - Expression of the mu opioid receptor (MOR1) protein is regulated temporally and
      spatially. Although transcription of its gene has been studied extensively,
      regulation of MOR1 protein production at the level of translation is poorly
      understood. Using reporter assays, we found that the MOR1 3'-untranslated region
      (UTR) represses reporter expression at the post-transcriptional level.
      Suppression by the 3'-UTR of MOR1 is mediated through decreased mRNA association
      with polysomes, which requires microRNA23b (miRNA23b), a specific miRNA that is
      expressed in mouse brain and NS20Y mouse neuroblastoma cells. miRNA23b interacts
      with the MOR1 3'-UTR via a K box motif. By knocking down endogenous miRNA23b in
      NS20Y cells, we confirmed that miRNA23b inhibits MOR1 protein expression in vivo.
      This is the first study reporting a translationally repressive role for the MOR1
      3'-UTR. We propose a mechanism in which miRNA23b blocks the association of MOR1
      mRNA with polysomes, thereby arresting its translation and suppressing the
      production of MOR1 protein.

PMID- 18716032
TI  - Systems-level studies of glycosyltransferase gene expression and enzyme activity
      that are associated with the selectin binding function of human leukocytes.
AB  - The application of systems biology methods in the emerging field of glycomics
      requires the collection and integration of glycosyltransferase data at the gene
      and enzyme level for the purpose of hypothesis generation. We systematically
      examined the relationship between gene expression, glycosyltransferase activity,
      glycan expression, and selectin-binding function in different systems, including
      human neutrophils, undifferentiated HL-60 (human promyelocytic cells),
      differentiated HL-60, and HL-60 synchronized in specific growth phases. Results
      demonstrate that 1) the sLe(X) (sialyl-Lewis-X) epitope is expressed in P
      selectin glycoprotein ligand-1 (PSGL-1) from neutrophils at higher levels
      compared with HL-60. This variation may be due to differences in the relative
      activities of alpha1,3-fucosyltransferases and alpha2,3-sialyltransferases in
      these two cell types. 2) HL-60 cell differentiation along granulocyte lineage
      increased the activity of beta1,4GalT and beta1,3GlcNAcT by 1.6- to 3.2-fold.
      This may contribute to LacNAc chain extension as evidenced by the 1.7-fold
      increase in DSA-lectin (lectin recognizing LacNAc) binding to cells after
      differentiation. 3) The activity of enzymes contributing to sLe(X) formation in
      leukocytes likely varies as ST3[Galbeta1,4GlcNAc] < or = alpha1,3FT[sialyl
      LacNAc] < beta1,3GlcNAcT. 4) O-glycan specific glycosyltransferase activity does
      not undergo periodic variation with cell cycle phases. Overall, gene expression
      and enzyme activity data combined with knowledge of biochemistry can predict the
      resulting glycan structures and yield viable experimentally testable hypothesis.

PMID- 18716035
TI  - Skeletal muscle type comparison of pyruvate dehydrogenase phosphatase activity
      and isoform expression: effects of obesity and endurance training.
AB  - Pyruvate dehydrogenase (PDH) plays an important role in regulating carbohydrate
      metabolism in skeletal muscle. PDH is activated by PDH phosphatase (PDP) and
      deactivated by PDH kinase (PDK). Obesity has a large negative impact on skeletal
      muscle carbohydrate metabolism, whereas endurance training has been shown to
      improve regulatory control of skeletal muscle carbohydrate metabolism, more so
      when coupled with obesity. A majority of this literature has focused on PDK, with
      little information available on PDP. To determine the relative role of PDP in
      regulating skeletal muscle PDH activity with obesity and endurance training,
      obese and lean Zucker rats remained sedentary or were endurance trained (1 h/day,
      5 days/wk) for a period of 8 wk. Soleus, red gastrocnemius, (RG), and white
      gastrocnemius (WG) muscles were sampled after the training period. The main
      findings were 1) obesity resulted in a 46% decrease in PDP activity expressed per
      milligram extracted mitochondrial protein only in RG, while PDP isoform content
      was unchanged; 2) 8 wk of endurance training led to a significant 1.4-2.2-fold
      increase in PDP activity of all muscle examined from obese rats, and the
      concomitant increase in PDP1 protein was only seen in soleus and RG; 3) 8 wk of
      endurance training led to a trending 1.4-2.2-fold increase in PDP activity of all
      muscle examined from obese rats, and the concomitant increase in PDP1 protein was
      only seen in soleus and RG; and 4) PDP2 protein content was not affected by
      obesity or training. These results suggest that decreased PDP activity in
      oxidative skeletal muscles may play a role in the impairment of carbohydrate
      metabolism in obese rats, which is reversible with endurance training.

PMID- 18716034
TI  - Local circuit input to the medullary reticular formation from the rostral nucleus
      of the solitary tract.
AB  - The intermediate reticular formation (IRt) subjacent to the rostral (gustatory)
      nucleus of the solitary tract (rNST) receives projections from the rNST and
      appears essential to the expression of taste-elicited ingestion and rejection
      responses. We used whole cell patch-clamp recording and calcium imaging to
      characterize responses from an identified population of prehypoglossal neurons in
      the IRt to electrical stimulation of the rNST in a neonatal rat pup slice
      preparation. The calcium imaging studies indicated that IRt neurons could be
      activated by rNST stimulation and that many neurons were under tonic inhibition.
      Whole cell patch-clamp recording revealed mono- and polysynaptic projections from
      the rNST to identified prehypoglossal neurons. The projection was primarily
      excitatory and glutamatergic; however, there were some inhibitory GABAergic
      projections, and many neurons received excitatory and inhibitory inputs. There
      was also evidence of disinhibition. Overall, bath application of GABA(A)
      antagonists increased the amplitude of excitatory currents, and, in several
      neurons, stimulation of the rNST systematically decreased inhibitory currents. We
      have hypothesized that the transition from licks to gapes by natural stimuli,
      such as quinine monohydrochloride, could occur via such disinhibition. We present
      an updated dynamic model that summarizes the complex synaptic interface between
      the rNST and the IRt and demonstrates how inhibition could contribute to the
      transition from ingestion to rejection.

PMID- 18716036
TI  - Alpha-adrenoceptor blockade modifies neurally induced atrial arrhythmias.
AB  - Our objective was to determine whether neuronally induced atrial arrhythmias can
      be modified by alpha-adrenergic receptor blockade. In 30 anesthetized dogs,
      trains of five electrical stimuli (1 mA; 1 ms) were delivered immediately after
      the P wave of the ECG to mediastinal nerves associated with the superior vena
      cava. Regional atrial electrical events were monitored with 191 atrial unipolar
      electrodes. Mediastinal nerve sites were identified that reproducibly initiated
      atrial arrhythmias. These sites were then restimulated following 1 h (time
      control, n = 6), or the intravenous administration of naftopidil (alpha(1)
      adrenergic blocker: 0.2 mg/kg, n = 6), yohimbine (alpha(2)-adrenergic blocker: 1
      mg/kg, n = 6) or both (n = 8). A ganglionic blocker (hexamethonium: 1 mg/kg) was
      tested in four dogs. Stimulation of mediastinal nerves sites consistently
      elicited atrial tachyarrhythmias. Repeat stimulation after 1 h in the time
      control group exerted a 19% decrease of the sites still able to induce atrial
      tachyarrhythmias. Hexamethonium inactivated 78% of the previously active sites.
      Combined alpha-adrenoceptor blockade inactivated 72% of the previously active
      sites. Bradycardia responses induced by mediastinal nerve stimulation were
      blunted by hexamethonium, but not by alpha(1,2)-adrenergic blockade. Naftopidil
      or yohimbine alone eliminated atrial arrhythmia induction from 31% and 34% of the
      sites (similar to time control). We conclude that heterogeneous activation of the
      intrinsic cardiac nervous system results in atrial arrhythmias that involve
      intrinsic cardiac neuronal alpha-adrenoceptors. In contrast to the global
      suppression exerted by hexamethonium, we conclude that alpha-adrenoceptor
      blockade targets intrinsic cardiac local circuit neurons involved in arrhythmia
      formation and not the flow-through efferent projections of the cardiac nervous
      system.

PMID- 18716037
TI  - Novel cryopreservation method for dissociated human embryonic stem cells in the
      presence of a ROCK inhibitor.
AB  - BACKGROUND: Human embryonic stem cells (hESCs) have potential use in clinical
      therapy and regenerative medicine. One of the major challenges regarding the
      application of these cells is the development of an efficient cryopreservation
      protocol, since current methods, which include slow-freezing-rapid thawing and
      vitrification of colonies in suspension, present poor viability and high
      differentiation rates. Dissociated hESC suspensions do not survive
      cryopreservation because they are susceptible to apoptosis upon cell detachment
      and dissociation. A selective Rho-associated kinase (ROCK) inhibitor has been
      reported to increase the survival of dissociated hESCs and their cloning
      efficiency. METHODS AND RESULTS: Here, we describe a novel method for dissociated
      hESCs cryopreservation in the presence of the ROCK inhibitor Y-27632. The
      addition of this inhibitor to the freezing and post-thawing medium significantly
      increased the survival rate and efficiency of colony formation. Moreover, the
      hESC colonies obtained after the cryopreservation in the presence of the ROCK
      inhibitor showed a very low rate of differentiation and a reduced time of
      recovery. After prolonged culture of frozen-thawed dissociated hESCs, the
      characteristic properties of pluripotent cells were observed, including normal
      karyotype, morphological features, marker expression (SSEA-4, TRA-1-60, TRA-1-81
      and Oct-4) and the potential to differentiate into derivatives of all three germ
      layers after embryoid bodies formation. CONCLUSION: This novel method for the
      cryopreservation of dissociated hESCs may reduce the time required to amplify
      frozen stocks, and facilitate not only the storage of large numbers of hESCs but
      also the widespread use of these cells in regenerative medicine.

PMID- 18716039
TI  - Androgen priming before ovarian stimulation for IVF.

PMID- 18716038
TI  - Fibromuscular differentiation in deeply infiltrating endometriosis is a reaction
      of resident fibroblasts to the presence of ectopic endometrium.
AB  - BACKGROUND: In this study, we characterized the fibromuscular (FM) tissue,
      typical of deeply infiltrating endometriosis, investigated which cells are
      responsible for the FM reaction and evaluated whether transforming growth factor
      beta (TGF-beta) signaling is involved in this process. METHODS: FM
      differentiation and TGF-beta signaling were assessed in deeply infiltrating
      endometriosis lesions (n = 20) and a nude mouse model of endometriosis 1, 2, 3
      and 4 weeks post-transplantation. The FM reaction was evaluated by
      immunohistochemistry using different markers of FM and smooth muscle cell
      differentiation (vimentin, desmin, alpha-smooth muscle actin, smooth muscle
      myosin heavy chain). TGF-beta signaling was assessed by immunostaining for its
      receptors and phosphorylated Smad. RESULTS: Deeply infiltrating endometriosis
      lesions contain myofibroblast-like cells that express multiple markers of FM
      differentiation. Expression of TGF-beta receptors and phospho-Smad was more
      pronounced in the endometrial component of the lesions than in the FM component.
      In the nude mouse model, alpha-smooth muscle actin expression was observed in
      murine fibroblasts surrounding the lesion, but not in human endometrial stroma.
      CONCLUSIONS: FM differentiation in deeply infiltrating endometriosis is the
      result of a reaction of the local environment to the presence of ectopic
      endometrium. It shares characteristics with pathological wound healing, but
      cannot be explained by TGF-beta signaling alone.

PMID- 18716040
TI  - Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells
      from patients with endometriosis.
AB  - BACKGROUND: Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, also has
      anti-proliferative properties and pro-apoptotic effects on different in vivo and
      in vitro models, two actions that may be efficacious in therapy for
      endometriosis. We evaluated the effects of celecoxib on apoptosis and
      proliferation, and vascular endothelial growth factor (VEGF) production and COX-2
      expression and activity in endometrial epithelial cells (EECs). METHODS AND
      RESULTS: Thirty-two endometriosis and 13 control women were included in the
      study. EECs from eutopic endometrium and control biopsies were cultured with
      different doses of celecoxib. Celecoxib at 50, 75 and 100 microM (versus vehicle
      control) inhibited EEC proliferation in cultures from controls (P < 0.05, P <
      0.01 and P < 0.01, respectively) and patients with endometriosis (P < 0.05, P <
      0.01 and P < 0.01), as assessed by (3)H-thymidine uptake. Celecoxib at 50, 75 and
      100 microM induced apoptosis in EEC from controls (P < 0.05, P < 0.001 and P <
      0.001) and patients with endometriosis (P < 0.001, P < 0.001 and P < 0.01), as
      revealed by the Acridine Orange-Ethidium Bromide technique. Western blot analysis
      showed that celecoxib was effective at increasing COX-2 protein at 100 microM in
      EEC from endometriosis patients (P < 0.05). In EEC from endometriosis patients,
      celecoxib at 25, 50 and 100 microM was also effective in reducing COX-2 activity,
      reflected in the reduction of prostaglandin E(2) (PGE(2)) synthesis (P < 0.001),
      and VEGF secretion (P < 0.001; P < 0.05 and P < 0.001), assessed by enzyme-linked
      immunosorbent assay. Exogenous PGE(2) did not reverse celecoxib-induced growth
      inhibition. CONCLUSIONS: This study suggests a direct effect of celecoxib on
      reduction of endometrial growth and supports further research on selective COX-2
      inhibition as a novel therapeutic modality in endometriosis.

PMID- 18716042
TI  - The roles of ingroup identification and outgroup entitativity in intergroup
      retribution.
AB  - A new aspect of intergroup conflict was investigated- vicarious retribution-in
      which neither the agent of retribution nor the target of retribution are directly
      involved in the initial intergroup provocation. The underlying processes involved
      in vicarious intergroup retribution were tested correlationally (Study 1) and
      experimentally (Study 2). Both ingroup identification and outgroup entitativity
      predict the degree of vicarious retribution. In both studies, there was evidence
      of motivated cognition, specifically that highly identified individuals perceived
      the outgroup as higher in entitativity than individuals low in identification.
      Structural equation modeling demonstrated that part of the effect of
      identification on retribution against the outgroup was mediated through
      perceptions of entitativity.

PMID- 18716041
TI  - Predictive factors of outcome and tumor response to systemic chemotherapy in
      patients with metastatic hepatocellular carcinoma.
AB  - OBJECTIVE: Systemic chemotherapy is an important treatment modality for
      metastatic hepatocellular carcinoma (HCC); however, the predictive factors of
      outcome and tumor response have not been fully investigated. The aim of this
      study was to identify factors that could be used to predict outcome and tumor
      response to systemic chemotherapy in patients with metastatic HCC. METHODS: We
      retrospectively examined 82 consecutive patients with metastatic HCC undergoing
      systemic chemotherapy to investigate factors associated with outcome and tumor
      response. The patients underwent 5-fluorouracil, mitoxantrone and cisplatin (FMP)
      therapy. RESULTS: The overall objective response rate was 22% (95% confidence
      interval, 14-32), and the median survival time and 1-year survival for all
      patients were 11.2 months and 43.5%, respectively. Multivariate analysis
      demonstrated that the absence of radiologically active intrahepatic disease (P =
      0.02) and ascites (P = 0.002) was independent favorable prognostic factors.
      Although multivariate analysis revealed no significant predictive factors of
      tumor response, the response rates in patients without radiologically active
      intrahepatic disease (response rate, 46%) tended to be higher than those in
      patients with active intrahepatic disease (response rate, 17%) (P = 0.05).
      CONCLUSION: Patients with metastatic HCC, who had sufficient hepatic function and
      no radiologically active intrahepatic disease, might be good candidates for
      systemic chemotherapy.

PMID- 18716043
TI  - Learning social attitudes: children's sensitivity to the nonverbal behaviors of
      adult models during interracial interactions.
AB  - White children show marked ingroup race preferences and a relative devaluation of
      Black people. The origin of these early interracial attitudes is to a large
      extent still unclear. The studies here test the possibility that preschool-aged
      children are particularly sensitive to the nonverbal behaviors performed by White
      adults during interracial interactions. In Study 1, children were shown a video
      displaying an interaction between a White and a Black adult. Across conditions,
      the White adult's verbal behaviors were either friendly or neutral, whereas his
      nonverbal behaviors showed either easiness (e.g., closeness, high eye contact) or
      uneasiness (e.g., distance, avoidance of eye contact). Results revealed that
      participants shaped their attitudes toward the Black target accordingly,
      independently from the White adults' verbal behaviors. Study 2 replicated the
      basic findings and demonstrated that the observed effects generalized to other
      Black targets. Results are discussed in relation to current approaches to
      understanding the formation of racial attitudes among children.

PMID- 18716044
TI  - Endurance exercise as a countermeasure for aging.
AB  - OBJECTIVE: We determined whether reduced insulin sensitivity, mitochondrial
      dysfunction, and other age-related dysfunctions are inevitable consequences of
      aging or secondary to physical inactivity. RESEARCH DESIGN AND METHODS: Insulin
      sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production
      in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary
      and endurance-trained young (18-30 years old) and older (59-76 years old)
      subjects. Expression of proteins involved in fuel metabolism was measured by mass
      spectrometry. Citrate synthase activity, mitochondrial DNA (mtDNA) abundance, and
      expression of nuclear-encoded transcription factors for mitochondrial biogenesis
      were measured. SIRT3, a mitochondrial sirtuin linked to lifespan-enhancing
      effects of caloric restriction, was measured by immunoblot. RESULTS: Insulin
      induced glucose disposal and suppression of endogenous glucose production were
      higher in the trained young and older subjects, but no age effect was noted. Age
      related decline in mitochondrial oxidative capacity was absent in endurance
      trained individuals. Although endurance-trained individuals exhibited higher
      expression of mitochondrial proteins, mtDNA, and mitochondrial transcription
      factors, there were persisting effects of age. SIRT3 expression was lower with
      age in sedentary but equally elevated regardless of age in endurance-trained
      individuals. CONCLUSIONS: The results demonstrate that reduced insulin
      sensitivity is likely related to changes in adiposity and to physical inactivity
      rather than being an inevitable consequence of aging. The results also show that
      regular endurance exercise partly normalizes age-related mitochondrial
      dysfunction, although there are persisting effects of age on mtDNA abundance and
      expression of nuclear transcription factors and mitochondrial protein.
      Furthermore, exercise may promote longevity through pathways common to effects of
      caloric restriction.

PMID- 18716045
TI  - Peripheral, but not central, CB1 antagonism provides food intake-independent
      metabolic benefits in diet-induced obese rats.
AB  - OBJECTIVE: Blockade of the CB1 receptor is one of the promising strategies for
      the treatment of obesity. Although antagonists suppress food intake and reduce
      body weight, the role of central versus peripheral CB1 activation on weight loss
      and related metabolic parameters remains to be elucidated. We therefore
      specifically assessed and compared the respective potential relevance of central
      nervous system (CNS) versus peripheral CB1 receptors in the regulation of energy
      homeostasis and lipid and glucose metabolism in diet-induced obese (DIO) rats.
      RESEARCH DESIGN AND METHODS: Both lean and DIO rats were used for our
      experiments. The expression of key enzymes involved in lipid metabolism was
      measured by real-time PCR, and euglycemic-hyperinsulinemic clamps were used for
      insulin sensitivity and glucose metabolism studies. RESULTS: Specific CNS-CB1
      blockade decreased body weight and food intake but, independent of those effects,
      had no beneficial influence on peripheral lipid and glucose metabolism.
      Peripheral treatment with CB1 antagonist (Rimonabant) also reduced food intake
      and body weight but, in addition, independently triggered lipid mobilization
      pathways in white adipose tissue and cellular glucose uptake. Insulin sensitivity
      and skeletal muscle glucose uptake were enhanced, while hepatic glucose
      production was decreased during peripheral infusion of the CB1 antagonist.
      However, these effects depended on the antagonist-elicited reduction of food
      intake. CONCLUSIONS: Several relevant metabolic processes appear to independently
      benefit from peripheral blockade of CB1, while CNS-CB1 blockade alone
      predominantly affects food intake and body weight.

PMID- 18716046
TI  - Measles outbreak in Qassim, Saudi Arabia 2007: epidemiology and evaluation of
      outbreak response.
AB  - BACKGROUND: Worldwide efforts for measles elimination are made possible due to
      the availability of a highly effective measles vaccine. In spite of highly
      vaccinated population, a measles outbreak occurred in Qassim province of Saudi
      Arabia, during January-August 2007. METHODS: An outbreak investigation was
      conducted to describe the epidemiology of outbreak. An audit of performance of
      control measures taken by the Primary Health Care team was done according to
      World Health Organization standards. RESULTS: Of 230 cases reported, more than
      one-third (37.8%) patients were 0-4 years of age. Children aged 6-11 months
      accounted for 51.7% cases amongst 0-4 years age group. The performance indicator
      targets of >or=80% for outbreak control measures were achieved regarding
      investigation of cases within 48 hours, and blood sample extraction within the
      optimal period. However, 66.8% cases reported within 48 hours of rash onset and
      only 16.4% of laboratory test results were received within 7 days of receipt of
      the specimen in laboratory. CONCLUSION: This outbreak demonstrates the increased
      susceptibility of unvaccinated children aged 6-11 months. To prevent future
      outbreaks, community awareness, review of measles vaccination schedule, enhanced
      surveillance and measles 'catch-up' mass immunization campaign to interrupt
      chains of transmission, are required.

PMID- 18716047
TI  - Low priority main reason not to participate in a colorectal cancer screening
      program with a faecal occult blood test.
AB  - BACKGROUND: Compared with screening programs for breast and cervical cancer,
      reported participation rates for colorectal cancer (CRC) screening are low. The
      effectiveness of a screening program is strongly influenced by the participation
      rate. The aim of this study was to investigate the main reasons not to
      participate in a population-based, invitational CRC screening program. METHODS:
      In the Dutch study program for CRC screening, a random selection of 20 623
      persons were invited received a faecal occult blood test. Of the non
      participants, 500 were randomly selected and contacted for a standardized
      telephone interview from November 2006 to May 2007 to document the main reason
      not to participate. RESULTS: In total, 312 (62%) non-participants could be
      included for analysis. Most frequently, reported reasons for non-participation
      were time-related or priority-related (36%), including 'did not notice test in
      mailbox' (13%) and 'forgot' (8%). Other reasons were health-related issues, such
      as 'severe illness' (9%), or emotional reasons, such as 'family circumstances'
      (7%). CONCLUSIONS: The majority of the reported reasons not to participate
      reflect low priority for screening. Adding extra instructions and information,
      and addressing specific concerns through additional interventions should be
      considered to improve individual decision-making about participation in future
      CRC population-based screening programs.

PMID- 18716048
TI  - Euglycemic hyperinsulinemia alters the response to orthostatic stress in older
      adults with type 2 diabetes.
AB  - OBJECTIVE: Insulin has opposing influences on blood pressure by simultaneously
      increasing adrenergic activity and vasodilatating peripheral blood vessels. In
      this study, we sought to determine whether hyperinsulinemia affects tilt table
      responses in older adults with type 2 diabetes not complicated by orthostatic
      hypotension. RESEARCH DESIGN AND METHODS: Twenty-two older adults (mean age 71.7
      +/- 1.1) with diet-controlled or oral hypoglycemic drug-controlled type 2
      diabetes were recruited. All subjects with orthostatic hypotension, diabetic
      nephropathy, and sensory neuropathy were excluded. Subjects underwent euglycemic
      hyperinsulinemic clamp and placebo "sham clamp" sessions. Sequential euglycemic
      hyperinsulinemic clamps were performed for 2 h at 40 mU x m(-2) x min(-1) (low
      dose) and 2 h at 80 mU x m(-2) x min(-1) (high dose), and each was followed by a
      head-up tilt table test at 70 degrees C for 10 min. RESULTS: There were no
      incidents of presyncope during the sham clamp, whereas there were four
      presyncopal events during both the low-dose and high-dose tilts. Although the low
      dose clamp showed no difference in the response between sessions (two-way ANOVA),
      subjects demonstrated a significantly larger decrease in mean arterial pressure
      (P = 0.005) and diastolic blood pressure (P = 0.08) during the high-dose tilt.
      Doppler measures of middle cerebral artery velocity were no different between the
      two sessions at either dose. CONCLUSIONS: The vasodilatory response to insulin
      can unmask orthostatic intolerance in older adults with type 2 diabetes,
      resulting in presyncopal symptoms. This could contribute to orthostatic
      hypotension in combination with other factors such as hyperthermia, hypovolemia,
      and adverse effects from medications.

PMID- 18716049
TI  - Aldose reductase genotypes and cardiorenal complications: an 8-year prospective
      analysis of 1,074 type 2 diabetic patients.
AB  - OBJECTIVE: We report the independent risk association of type 2 diabetic
      nephropathy with the z-2 allele of the 5'-(CA)(n) microsatellite and C-106T
      promoter polymorphisms of the aldose reductase gene (ALR2) using a case-control
      design. In this expanded cohort, we examined their predictive roles on new onset
      of cardiorenal complications using a prospective design. RESEARCH DESIGN AND
      METHODS: In this 8-year prospective cohort of 1,074 type 2 diabetic patients (59%
      male, median age 61 years; disease duration 7 years) with an observation period
      of 8,592 person-years, none had clinical evidence of coronary heart disease (CHD)
      or chronic kidney disease at recruitment. The renal end point was defined as new
      onset of estimated glomerular filtration rate <60 ml/min per 1.72 m(2) or
      hospitalizations with dialysis or death due to renal disease, and CHD was defined
      as hospitalizations with myocardial infarction, ischemic heart disease, or
      related deaths. RESULTS: After controlling for baseline risk factors and use of
      medications, we found that the ALR2 z-2 allele of (CA)(n) microsatellite carriers
      had increased risk of renal (hazard ratio 1.53 [95% CI 1.14-2.05], P = 0.005) or
      combined cardiorenal (1.31 [1.01-1.72], P = 0.047) end points. Carriers of the
      ALR2 C-106T polymorphism also had increased risk of renal (1.54 [1.15-2.07], P =
      0.004) and cardiorenal (1.49 [1.14-1.95], P = 0.004) end points. Compared with
      noncarriers, patients with two risk-conferring genotypes had a twofold increased
      risk of renal (2.41 [1.57-3.70], P < 0.001) and cardiorenal (1.94 [1.29-2.91], P
      = 0.002) end points. CONCLUSIONS: In Chinese type 2 diabetic patients, genetic
      polymorphisms of ALR2 independently predicted new onset of renal and cardiorenal
      end points, with the latter being largely mediated through renal disease.

PMID- 18716050
TI  - Normal glucose values are associated with a lower risk of mortality in
      hospitalized patients.
AB  - OBJECTIVE: Hyperglycemia is a common condition in hospitalized patients. The aim
      of this study was to investigate the relationships between glycemia upon
      admission and mortality in a heterogeneous group of adult patients. RESEARCH
      DESIGN AND METHODS: The 3-year records released from a general hospital were
      associated with a plasma glucose dataset of its general laboratory. A matched
      case-control study was implemented (3,338 case-control subject pairs). All
      patient refined diagnosis-related groups and the relative risk of death were the
      matching criteria. A multivariate conditional logistic regression model was used
      to evaluate the associations between death and glycemia. RESULTS: Higher in
      hospital mortality was associated with hyperglycemia or hypoglycemia, whereas
      lower risk was observed for values between 78 and 101 mg/dl. CONCLUSIONS: Our
      data confirm the relation between glycemia upon admission and mortality and
      suggest that slightly increased or decreased plasma glucose can be linked with
      increased mortality risk.

PMID- 18716051
TI  - Sprint training increases muscle oxidative metabolism during high-intensity
      exercise in patients with type 1 diabetes.
AB  - OBJECTIVE: To investigate sprint-training effects on muscle metabolism during
      exercise in subjects with (type 1 diabetic group) and without (control group)
      type 1 diabetes. RESEARCH DESIGN AND METHODS: Eight subjects with type 1 diabetes
      and seven control subjects, matched for age, BMI, and maximum oxygen uptake
      (Vo(2peak)), undertook 7 weeks of sprint training. Pretraining, subjects cycled
      to exhaustion at 130% Vo(2peak). Posttraining subjects performed an identical
      test. Vastus lateralis biopsies at rest and immediately after exercise were
      assayed for metabolites, high-energy phosphates, and enzymes. Arterialized venous
      blood drawn at rest and after exercise was analyzed for lactate and [H(+)].
      Respiratory measures were obtained on separate days during identical tests and
      during submaximal tests before and after training. RESULTS: Pretraining, maximal
      resting activities of hexokinase, citrate synthase, and pyruvate dehydrogenase
      did not differ between groups. Muscle lactate accumulation with exercise was
      higher in type 1 diabetic than nondiabetic subjects and corresponded to indexes
      of glycemia (A1C, fasting plasma glucose); however, glycogenolytic and glycolytic
      rates were similar. Posttraining, at rest, hexokinase activity increased in type
      1 diabetic subjects; in both groups, citrate synthase activity increased and
      pyruvate dehydrogenase activity decreased; during submaximal exercise, fat
      oxidation was higher; and during intense exercise, peak ventilation and carbon
      dioxide output, plasma lactate and [H(+)], muscle lactate, glycogenolytic and
      glycolytic rates, and ATP degradation were lower in both groups. CONCLUSIONS:
      High-intensity exercise training was well tolerated, reduced metabolic
      destabilization (of lactate, H(+), glycogenolysis/glycolysis, and ATP) during
      intense exercise, and enhanced muscle oxidative metabolism in young adults with
      type 1 diabetes. The latter may have clinically important health benefits.

PMID- 18716052
TI  - Understanding pluripotency--how embryonic stem cells keep their options open.
AB  - Embryonic stem (ES) cells have the capacity to proliferate indefinitely in
      culture while maintaining the ability to differentiate to form any of the cells
      of the body. This unique combination of functions suggests that these cells could
      provide a potentially unlimited source of differentiated cells for the treatment
      of disease and aging. Understanding the molecular processes that underpin these
      functions in ES cells will allow us to harness their potential and develop
      strategies that control their differentiation. Combination of controlled
      differentiation with ground-breaking technologies for the reversal of somatic
      cells to an ES cell-like state promise the generation of patient-derived
      pluripotent cell lines for the treatment of disease in the future.

PMID- 18716053
TI  - Identification and characterization of human embryonic poly(A) binding protein
      (EPAB).
AB  - Transcriptional silencing that begins with oocyte maturation persists during the
      initial mitotic divisions of the embryo. Gene expression during this period
      largely depends on the translational activation of maternal mRNAs by cytoplasmic
      polyadenylation and requires an embryonic poly(A) binding protein (EPAB). EPAB
      has been identified in Xenopus and mouse, where it is expressed exclusively in
      oocytes and early embryos until zygotic genome activation (ZGA) when it is
      replaced by the somatic cytoplasmic poly(A) binding protein (PABPC1). EPAB plays
      a central role in the regulation of maternal mRNA activation by preventing
      deadenylation and promoting translation. In this study, we identified and
      characterized the human EPAB ortholog. Human EPAB is a 619 amino acid protein
      with 77% identity and 84% similarity to mouse EPAB. Human EPAB mRNA is detected
      in ovaries, testes and several somatic tissues including pancreas, liver and
      thymus. Similar to the observations in Xenopus and mouse, human EPAB is the
      predominant poly(A) binding protein in immature (germinal vesicle) and mature
      (metaphase II) oocytes, and it is replaced by PABPC1 following ZGA, which occurs
      at 4- to 8-cell stage in human. Our findings suggest that the unique
      translational regulatory pathways that control gene expression during oogenesis
      and early embryo development may be common between model organisms and humans.

PMID- 18716054
TI  - CLASP modulates microtubule-cortex interaction during self-organization of
      acentrosomal microtubules.
AB  - CLASP proteins associate with either the plus ends or sidewalls of microtubules
      depending on the subcellular location and cell type. In plant cells, CLASP's
      distribution along the full length of microtubules corresponds with the uniform
      anchorage of microtubules to the cell cortex. Using live cell imaging, we show
      here that loss of CLASP in Arabidopsis thaliana results in partial detachment of
      microtubules from the cortex. The detached portions undergo extensive waving,
      distortion, and changes in orientation, particularly when exposed to the forces
      of cytoplasmic streaming. These deviations from the normal linear polymerization
      trajectories increase the likelihood of intermicrotubule encounters that are
      favorable for subsequent bundle formation. Consistent with this, cortical
      microtubules in clasp-1 leaf epidermal cells are hyper-parallel. On the basis of
      these data, we identify a novel mechanism where modulation of CLASP activity
      governs microtubule-cortex attachment, thereby contributing to self-organization
      of cortical microtubules.

PMID- 18716055
TI  - Microtubule-mediated Src tyrosine kinase trafficking in neuronal growth cones.
AB  - Src family tyrosine kinases are important signaling enzymes in the neuronal
      growth cone, and they have been implicated in axon guidance; however, the
      detailed localization, trafficking, and cellular functions of Src kinases in live
      growth cones are unclear. Here, we cloned two novel Aplysia Src kinases, termed
      Src1 and Src2, and we show their association with both the plasma membrane and
      the microtubule cytoskeleton in the growth cone by live cell imaging,
      immunocytochemistry, and cell fractionation. Activated Src2 is enriched in
      filopodia tips. Interestingly, Src2-enhanced green fluorescent protein-positive
      endocytic vesicles and tubulovesicular structures undergo microtubule-mediated
      movements that are bidirectional in the central domain and mainly retrograde in
      the peripheral domain. To further test the role of microtubules in Src
      trafficking in the growth cone, microtubules were depleted with either nocodazole
      or vinblastine treatment, resulting in an increase in Src2 plasma membrane levels
      in all growth cone domains. Our data suggest that microtubules regulate the
      steady-state level of active Src at the plasma membrane by mediating retrograde
      recycling of endocytosed Src. Expression of constitutively active Src2 results in
      longer filopodia that protrude from smaller growth cones, implicating Src2 in
      controlling the size of filopodia and lamellipodia.

PMID- 18716056
TI  - Lysosomal localization of ubiquitinated Jun requires multiple determinants in a
      lysine-27-linked polyubiquitin conjugate.
AB  - Ubiquitination regulates many cellular functions, including protein localization
      and degradation. Each function is specified by unique determinants in the
      conjugate. Ubiquitinated Jun is localized to lysosomes for degradation. Here, we
      characterized determinants of Jun ubiquitination and lysosomal localization by
      using ubiquitin-mediated fluorescence complementation (UbFC) in living cells and
      analysis of the stoichiometry of ubiquitin linked to Jun extracted from cells.
      The delta region of Jun and isoleucine-44 in ubiquitin were required for
      lysosomal localization of the conjugate. Ubiquitin containing only lysine-27, but
      no other single-lysine ubiquitin, mediated Jun ubiquitination, albeit at lower
      stoichiometry than wild-type ubiquitin. These conjugates were predominantly
      nuclear, but coexpression of lysine-27 and lysine-less ubiquitins enhanced the
      mean stoichiometry of Jun ubiquitination and lysosomal localization of the
      conjugate. Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) and
      tumor susceptibility gene 101 (TSG101) colocalized with ubiquitinated Jun.
      Knockdown of HRS or TSG101 inhibited lysosomal localization of ubiquitinated Jun
      and reduced Jun turnover. Ubiquitination of other Fos and Jun family proteins had
      distinct effects on their localization. Our results indicate that Jun is
      polyubiquitinated by E3 ligases that produce lysine-27-linked chains. Lysosomal
      localization of the conjugate requires determinants in Jun and in ubiquitin that
      are recognized in part by TSG101 and HRS, facilitating selective translocation
      and degradation of ubiquitinated Jun.

PMID- 18716057
TI  - Phosphatase inhibitor-2 balances protein phosphatase 1 and aurora B kinase for
      chromosome segregation and cytokinesis in human retinal epithelial cells.
AB  - Mitosis in Saccharomyces cerevisiae depends on IPL1 kinase, which genetically
      interacts with GLC8. The metazoan homologue of GLC8 is inhibitor-2 (I-2), but its
      function is not understood. We found endogenous and ectopic I-2 localized to the
      spindle, midzone, and midbody of mitotic human epithelial ARPE-19 cells.
      Knockdown of I-2 by RNA interference produced multinucleated cells, with
      supernumerary centrosomes, multipolar spindles and lagging chromosomes during
      anaphase. These defects did not involve changes in levels of protein phosphatase
      1 (PP1), and the multinuclear phenotype was rescued by overexpression of I-2.
      Appearance of multiple nuclei and supernumerary centrosomes required progression
      through the cell cycle and I-2 knockdown cells failed cytokinesis, as observed by
      time-lapse microscopy. Inhibition of Aurora B by hesperadin produced
      multinucleated cells and reduced H3S10 phosphorylation. I-2 knockdown enhanced
      this latter effect. Partial knockdown of PP1Calpha prevented multiple nuclei
      caused by either knockdown of I-2 or treatment with hesperadin. Expression of
      enhanced green fluorescent protein-I-2 or hemagglutinin-I-2 made cells resistant
      to hesperadin. We propose that I-2 acts to enhance Aurora B by inhibiting
      specific PP1 holoenzymes that dephosphorylate Aurora B substrates necessary for
      chromosome segregation and cytokinesis. Conserved together throughout eukaryotic
      evolution, I-2, PP1 and Aurora B function interdependently during mitosis.

PMID- 18716058
TI  - Regulation of Chk1 by its C-terminal domain.
AB  - Chk1 is a protein kinase that is the effector molecule in the G2 DNA damage
      checkpoint. Chk1 homologues have an N-terminal kinase domain, and a C-terminal
      domain of approximately 200 amino acids that contains activating phosphorylation
      sites for the ATM/R kinases, though the mechanism of activation remains unknown.
      Structural studies of the human Chk1 kinase domain show an open conformation; the
      activity of the kinase domain alone is substantially higher in vitro than full
      length Chk1, and coimmunoprecipitation studies suggest the C-terminal domain may
      contain an autoinhibitory activity. However, we show that truncation of the C
      terminal domain inactivates Chk1 in vivo. We identify additional mutations within
      the C-terminal domain that activate ectopically expressed Chk1 without the need
      for activating phosphorylation. When expressed from the endogenous locus,
      activated alleles show a temperature-sensitive loss of function, suggesting these
      mutations confer a semiactive state to the protein. Intragenic suppressors of
      these activated alleles cluster to regions in the catalytic domain on the face of
      the protein that interacts with substrate, suggesting these are the regions that
      interact with the C-terminal domain. Thus, rather than being an autoinhibitory
      domain, the C-terminus of Chk1 also contains domains critical for adopting an
      active configuration.

PMID- 18716059
TI  - Assembly and misassembly of cystic fibrosis transmembrane conductance regulator:
      folding defects caused by deletion of F508 occur before and after the calnexin
      dependent association of membrane spanning domain (MSD) 1 and MSD2.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a polytopic
      membrane protein that functions as a Cl(-) channel and consists of two membrane
      spanning domains (MSDs), two cytosolic nucleotide binding domains (NBDs), and a
      cytosolic regulatory domain. Cytosolic 70-kDa heat shock protein (Hsp70), and
      endoplasmic reticulum-localized calnexin are chaperones that facilitate CFTR
      biogenesis. Hsp70 functions in both the cotranslational folding and
      posttranslational degradation of CFTR. Yet, the mechanism for calnexin action in
      folding and quality control of CFTR is not clear. Investigation of this question
      revealed that calnexin is not essential for CFTR or CFTRDeltaF508 degradation. We
      identified a dependence on calnexin for proper assembly of CFTR's membrane
      spanning domains. Interestingly, efficient folding of NBD2 was also found to be
      dependent upon calnexin binding to CFTR. Furthermore, we identified folding
      defects caused by deletion of F508 that occurred before and after the calnexin
      dependent association of MSD1 and MSD2. Early folding defects are evident upon
      translation of the NBD1 and R-domain and are sensed by the RMA-1 ubiquitin ligase
      complex.

PMID- 18716060
TI  - The RHO1-specific GTPase-activating protein LRG1 regulates polar tip growth in
      parallel to Ndr kinase signaling in Neurospora.
AB  - Regulation of Rho GTPase signaling is critical for cell shape determination and
      polarity. Here, we investigated the role of LRG1, a novel member of the GTPase
      activating proteins (GAPs) of Neurospora crassa. LRG1 is essential for apical tip
      extension and to restrict excessive branch formation in subapical regions of the
      hypha and is involved in determining the size of the hyphal compartments. LRG1
      localizes to hyphal tips and sites of septation via its three LIM domains. The
      accumulation of LRG1 as an apical cap is dependent on a functional actin
      cytoskeleton and active growth, and is influenced by the opposing microtubule
      dependent motor proteins dynein and kinesin-1. Genetic evidence and in vitro
      GTPase assays identify LRG1 as a RHO1-specific GAP affecting several output
      pathways of RHO1, based on hyposensitivity to the glucan inhibitor caspofungin,
      synthetic lethality with a hyperactive beta1,3-glucan synthase mutant, altered
      PKC/MAK1 pathway activities, and hypersensitivity to latrunculin A. The
      morphological defects of lrg-1 are highly reminiscent to the Ndr kinase/RAM
      pathway mutants cot-1 and pod-6, and genetic evidence suggests that RHO1/LRG1
      function in parallel with COT1 in coordinating apical tip growth.

PMID- 18716061
TI  - Skp2 regulates G2/M progression in a p53-dependent manner.
AB  - Targeted proteasomal degradation mediated by E3 ubiquitin ligases controls cell
      cycle progression, and alterations in their activities likely contribute to
      malignant cell proliferation. S phase kinase-associated protein 2 (Skp2) is the F
      box component of an E3 ubiquitin ligase complex that targets p27(Kip1) and cyclin
      E1 to the proteasome. In human melanoma, Skp2 is highly expressed, regulated by
      mutant B-RAF, and required for cell growth. We show that Skp2 depletion in
      melanoma cells resulted in a tetraploid cell cycle arrest. Surprisingly, co
      knockdown of p27(Kip1) or cyclin E1 failed to prevent the tetraploid arrest
      induced by Skp2 knockdown. Enhanced Aurora A phosphorylation and repression of
      G2/M regulators cyclin B1, cyclin-dependent kinase 1, and cyclin A indicated a
      G2/early M phase arrest in Skp2-depleted cells. Furthermore, expression of
      nuclear localized cyclin B1 prevented tetraploid accumulation after Skp2
      knockdown. The p53 status is most frequently wild type in melanoma, and the
      tetraploid arrest and down-regulation of G2/M regulatory genes were strongly
      dependent on wild-type p53 expression. In mutant p53 melanoma lines, Skp2
      depletion did not induce cell cycle arrest despite up-regulation of p27(Kip1).
      These data indicate that elevated Skp2 expression may overcome p53-dependent cell
      cycle checkpoints in melanoma cells and highlight Skp2 actions that are
      independent of p27(Kip1) degradation.

PMID- 18716062
TI  - Erk5 controls Slug expression and keratinocyte activation during wound healing.
AB  - Reepithelialization during cutaneous wound healing involves numerous signals that
      result in basal keratinocyte activation, spreading, and migration, all linked to
      a loosening of cell-cell adhesion structures. The transcription factor Slug is
      required for this process, and EGF treatment of human keratinocytes induced
      activating phosphorylation of Erk5 that coincides with slug transcription.
      Accordingly, ectopic activation of Erk5 led to increased Slug mRNA levels and
      faster wound healing, whereas keratinocyte migration was totally blocked by Erk5
      pathway inhibition. Expression of a shRNA specific for Erk5 strongly diminished
      Erk5 levels in keratinocytes and significantly decreased their motility response
      to EGF, along with induction of Slug expression. These Erk5-deprived
      keratinocytes showed an altered, more compact morphology, along with disruption
      of desmosome organization. Accordingly, they displayed an altered ability to form
      cell aggregates. These results implicate a novel EGFR/Erk5/Slug pathway in the
      control of cytoskeleton organization and cell motility in keratinocytes treated
      with EGF.

PMID- 18716064
TI  - Hormonal, neural, and metabolic regulation of immunity.

PMID- 18716063
TI  - A novel functional screen in human cells identifies MOCA as a negative regulator
      of Wnt signaling.
AB  - Aberrant Wnt signal transduction is involved in many human diseases such as
      cancer and neurodegenerative disorders. The key effector protein of the canonical
      Wnt pathway is beta-catenin, which functions with T-cell factor/lymphoid enhancer
      factor (TCF/LEF) to activate gene transcription that leads to expression of Wnt
      target genes. In this study we provide results obtained from a novel functional
      screen of a human brain cDNA library used to identify 63 genes that are putative
      negative Wnt regulators. These genes were divided into eight functional groups
      that include known canonical and noncanonical Wnt pathway components and genes
      that had not yet been assigned to the Wnt pathway. One of the groups, the
      presenilin-binding proteins, contains the modifier of cell adhesion (MOCA) gene.
      We show that MOCA is a novel inhibitor of Wnt/beta-catenin signaling. MOCA forms
      a complex with beta-catenin and inhibits transcription of known Wnt target genes.
      Epistasis experiments indicate that MOCA acts to reduce the levels of nuclear
      beta-catenin, increase the levels of membrane-bound beta-catenin, and enhances
      cell-cell adhesion. Therefore, our data indicate that MOCA is a novel Wnt
      negative regulator and demonstrate that this screening approach can be a rapid
      means for isolation of new Wnt regulators.

PMID- 18716066
TI  - High-sensitive CaSO4:Dy thermoluminescent phosphor synthesis by co-precipitation
      technique.
AB  - This paper describes the successful development of the co-precipitation technique
      for the preparation of a high-sensitive dysprosium-doped calcium sulphate
      (CaSO(4):Dy) thermoluminescent dosimetry (TLD) phosphor with dosimetric glow peak
      at approximately 230 degrees C which is a desired development in the field of
      radiation protection dosimetry. The main advantages of this co-precipitation
      technique over the conventional recrystallisation technique of phosphor
      preparation are: (i) preparation time is very less; (ii) quantity of sulphuric
      acid evaporated is insignificant; (iii) higher TL sensitivity -20% more than the
      present material; (iv) better glow curve structure; (v) lesser glow peak shift
      and better linearity to gamma and (vi) uniform crystal morphology and lower grain
      size-all grains are mostly cuboidal in shape, quite uniform and small (average
      size about 25 microm), suitable for manufacturing teflon discs in as-prepared
      form. Optimum values of various parameters in the method of preparation for a
      batch of 20 g CaSO(4):Dy phosphors to obtain maximum TL sensitivity, with
      favourable glow curves are studied.

PMID- 18716065
TI  - Blockade of CXCL12/CXCR4 axis ameliorates murine experimental colitis.
AB  - Recent studies indicate that the CXCL12/CXCR4 interaction is involved in several
      inflammatory conditions. However, it is unclear whether this interaction has a
      role in the pathophysiology of inflammatory bowel disease (IBD). We investigated
      the significance of this interaction in patients with IBD and in mice with
      dextran sulfate sodium (DSS)-induced colitis and the effect of a CXCR4 antagonist
      on experimental colitis. First, we measured CXCR4 expression on peripheral T
      cells in patients with IBD. Furthermore, we investigated CXCR4 expression on
      leukocytes and CXCL12 expression in the colonic tissue of mice with DSS-induced
      colitis, and we evaluated the effects of a CXCR4 antagonist on DSS-induced
      colitis and colonic inflammation of interleukin (IL)-10 knockout (KO) mice.
      Colonic inflammation was assessed both clinically and histologically. Cytokine
      production from mesenteric lymph node cells was also examined. CXCR4 expression
      on peripheral T cells was significantly higher in patients with active ulcerative
      colitis (UC) compared with normal controls, and CXCR4 expression levels of UC
      patients correlated with disease activity. Both CXCR4 expression on leukocytes
      and CXCL12 expression in colonic tissue were significantly increased in mice with
      DSS-induced colitis. Administration of a CXCR4 antagonist ameliorated colonic
      inflammation in DSS-induced colitis and IL-10 KO mice. CXCR4 antagonist reduced
      tumor necrosis factor-alpha and interferon-gamma production from mesenteric lymph
      node cells, whereas it did not affect IL-10 production. The percentage of
      mesenteric Foxp3+CD25+ T cells in DSS-induced colitis was not affected by CXCR4
      antagonist. These results suggest that blockade of this chemokine axis might have
      potential as a therapeutic target for the treatment of IBD.

PMID- 18716067
TI  - Nontraumatic emergent neuroradiology: review and self-assessment module.
AB  - Objectiv: The educational objectives for this case-based self-assessment module
      on imaging of nontraumatic emergent neuroradiology are to use case examples to
      teach the imaging features of CT and MRI of emergent neuroradiologic diagnoses
      and to improve the reader's understanding of the pathophysiology and clinical
      management of each clinical scenario. Imaging plays a critical role in assessing
      patients with acute neurologic symptoms. CT is quick and easy to perform in an
      emergency setting and is often the technique of choice for any neurologic
      emergency situations. Clinical correlation is crucial for accurate diagnosis and
      triaging patients for further evaluation. Persistent or progressive neurologic
      symptoms despite negative CT should prompt other imaging studies. Conclusio: At
      the end of this self-assessment module, readers will be able to generate a
      concise list of differential diagnoses for imaging findings that often are
      encountered in patients with nontraumatic neurologic emergency.

PMID- 18716068
TI  - Radiological reasoning: submucosal laryngeal mass.

PMID- 18716069
TI  - Imaging of metastatic malignant melanoma to the head: self-assessment module.
AB  - The educational objectives for this self-assessment module on the imaging of
      metastatic malignant melanoma to the head are for the participant to exercise,
      self-assess, and improve his or her understanding of the features used to
      differentiate hemorrhagic neoplasms from benign nonneoplastic hematomas on MRI
      and to gain familiarity with the varied appearances of melanoma metastases to the
      head.

PMID- 18716070
TI  - AJR teaching file: acute onset headache.

PMID- 18716071
TI  - Imaging of osteosarcoma after irradiation: self-assessment module.
AB  - The educational objectives of this self-assessment module on the imaging of
      postirradiation osteosarcoma are for the participant to exercise, self-assess,
      and improve his or her understanding of the features used to establish the
      diagnosis of postirradiation sarcoma.

PMID- 18716072
TI  - AJR teaching file: lump on the head.

PMID- 18716073
TI  - AJR teaching file: symmetric demyelination.

PMID- 18716075
TI  - Radiological reasoning: leukocoria in a child.

PMID- 18716074
TI  - AJR teaching file: facial mass in a child.

PMID- 18716076
TI  - Screening CT colonography in an asymptomatic average-risk Asian population: a 2
      year experience in a single institution.
AB  - OBJECTIVE: The purpose of our study was to report the results of screening CT
      colonography (CTC) in an asymptomatic average-risk Asian population. MATERIALS
      AND METHODS: In 2005 and 2006, 1,015 Korean adults (609 men and 406 women; mean
      age, 51 years) underwent screening CTC using a 16-MDCT scanner and an automated
      CO2 delivery system. During the study period, the protocols were changed to use
      less vigorous purgation and lower radiation doses; fecal tagging (n = 890) and
      primary 3D interpretation (n = 966) were generally used. CTC results were
      categorized as C0, inadequate; C1, no significant polyp; C2, one or two 6- to 9
      mm polyps; C3, polyps > or = 10 mm or > or = three 6- to 9-mm polyps; and C4,
      mass. Patients with positive CTC results were referred to gastroenterologists for
      follow-up or management planning. RESULTS: Categories C0-C4 were assigned to 21
      (2.1%), 916 (90.2%), 54 (5.3%), 23 (2.3%), and one (0.1%) patients, respectively.
      Fifty-four patients with C4 (n = 1), C3 (n = 20), or C2 (n = 33) underwent
      subsequent optical colonoscopy: complete (n = 53) and incomplete (n = 1). Per
      patient positive predictive values (PPVs) for categories C3-C4 and C2-C4 were 90%
      (18/20) and 74% (39/53), respectively. Per-polyp PPVs at 10- and 6-mm thresholds
      were 92% (22/24) and 69% (45/65), respectively. The diagnostic yield for advanced
      neoplasm was 1.5% (15/1,015). CONCLUSION: Our results seem comparable to Western
      experiences, showing that a successful screening CTC program can be reproduced in
      an Asian population.

PMID- 18716077
TI  - Contrast-enhanced sonographic guidance for local injection of a hemostatic agent
      for management of blunt hepatic hemorrhage: a canine study.
AB  - OBJECTIVE: The purpose of this study was to determine whether injection of
      hemostatic agents directly into an injury site under the guidance of contrast
      enhanced sonography can effectively control hemorrhage due to hepatic trauma.
      MATERIALS AND METHODS: Fifteen mixed-breed dogs 2-3 years old and weighing 17-20
      kg were anesthetized with intramuscular pentobarbital sodium (30 mg/kg). A
      special impacting device was used to induce hepatic trauma with a mean force of
      5.3 +/- 0.3 kN. Twelve of the 15 dogs had hepatic injuries with a grade of 3-4 or
      4. The 12 dogs were divided into treatment and control groups. In the treatment
      group, hemocoagulase atrox (1 Klobusitzky unit) and alpha-cyanoacrylate (1 mL)
      were administered by transcutaneous injection into the injury site and the
      bleeding site, respectively, under the guidance of contrast-enhanced sonography.
      The control group received injections of 0.9% normal saline solution. RESULTS:
      After injection into the treatment group, no active bleeding was observed at the
      liver injury site. In the control group, evidence of active bleeding was present
      on contrast-enhanced sonograms. Laparotomy of the treatment group showed that
      hepatic injuries had been covered and adhered by clots and the glue membrane of
      the hemostatic agents and that free intraperitoneal blood volume was
      significantly less than in the control group (p < 0.001). Bleeding did not stop
      in the control group. CONCLUSION: In dogs, transcutaneous local injection of
      hemostatic agents can effectively reduce blood loss due to severe liver trauma.
      Because it is simple, convenient, and effective, the technique may be an
      alternative for bedside and battlefield management of hepatic hemorrhage due to
      trauma.

PMID- 18716078
TI  - Low-dose MDCT for surveillance of patients with severe homogeneous emphysema
      after bronchoscopic airway bypass.
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of low-dose
      MDCT for radiologic monitoring of patients who have undergone placement of
      bronchial stents for airway bypass. SUBJECTS AND METHODS: In a prospective study,
      seven patients underwent MDCT according to a low-dose protocol (40 mAs, 120 kVp)
      before and after stent placement. The positions of the stents in the segmental
      bronchi were analyzed and compared with the bronchoscopic findings, which were
      reference standard. Patency versus lack of patency of stents was classified with
      five levels of confidence, and a definitive diagnosis was assigned to each stent.
      Prediction of stent dislodgment, follow-up findings, and complications occurring
      during the observation period were recorded. Consensus reading was performed by
      two radiologists. Statistical analysis was conducted by receiver operating
      characteristic analysis or four-field table. RESULTS: Seven patients underwent
      implantation of 37 stents (mean, 5 +/- 2 [SD] stents per patient; range, 2-8
      stents). The area under the curve for differentiating patent from occluded stents
      was 0.995 with resulting sensitivity and specificity of 86.5% and 98.1%. The
      correct diagnosis of patency was established with MDCT for all but one stent
      (sensitivity, 94.7%; specificity, 100%). Sensitivity and specificity for
      prediction of dislodgment were 80% and 91%. Five stents were not identified
      during inspection bronchoscopy but were found in a regular position at MDCT.
      Three instances of minor bleeding and one of pneumothorax resolved spontaneously.
      The mean effective dose of the scan was 1.3 +/- 0.6 mSv. CONCLUSION: Low-dose
      MDCT is feasible for radiologic monitoring after airway bypass procedure.

PMID- 18716079
TI  - Perfusion CT of the brain using 40-mm-wide detector and toggling table technique
      for initial imaging of acute stroke.
AB  - OBJECTIVE: Limited coverage of the brain in the z-axis has been a drawback of
      perfusion CT. The purpose of this study was to evaluate the usefulness of
      perfusion CT with extended coverage in the z-axis for the assessment of acute
      stroke in an emergent clinical setting. MATERIALS AND METHODS: Fifty-eight
      patients who underwent 80-mm-coverage perfusion CT within 24 hours after stroke
      onset were included. Perfusion CT was performed using a 64-MDCT unit equipped
      with 40-mm-wide detector and the toggling table technique. Lesion detection by
      perfusion CT was analyzed using follow-up diffusion-weighted imaging and MR
      angiography as the reference standards. More conventional 20-mm-coverage
      perfusion CT was simulated by extracting data obtained at the basal ganglia level
      for comparison with 80-mm-coverage perfusion CT. RESULTS: Fifty-one patients had
      acute infarctions and seven patients did not. For 80-mm-coverage perfusion CT,
      perfusion abnormality was detected in 42 of 51 patients (sensitivity, 82.4%; and
      specificity, 85.7%). When patients with small artery disease (small acute
      infarctions in the basal ganglia, thalamus, corona radiata, and pons) were
      excluded, sensitivity increased to 92.3%. As compared with 80-mm-coverage
      perfusion CT, 20-mm-coverage perfusion CT missed nine acute infarctions located
      above or below the level of the basal ganglia (p = 0.0039). CONCLUSION: Perfusion
      CT with 80-mm-coverage was found to be useful as an initial imaging method in
      acute ischemic stroke, although it had low sensitivity for detecting small acute
      infarctions. In particular, this technique provided higher lesion detection than
      20-mm-coverage perfusion CT.

PMID- 18716080
TI  - In vitro assessment of a 3D segmentation algorithm based on the belief functions
      theory in calculating renal volumes by MRI.
AB  - OBJECTIVE: Renal volumetry is an essential part of split renal function
      assessment in MR urography. The aim of this study was to assess the accuracy and
      repeatability of a 3D segmentation algorithm based on the belief functions theory
      for calculating renal volumes from MR images. MATERIALS AND METHODS: The true
      volumes of 20 animal kidneys of various sizes were obtained by fluid
      displacement. Each kidney was examined using two different MR units. Three
      dimensional proton density-weighted acquisitions with an incremental slice
      thickness were performed. The MR volume was then measured with a segmentation
      algorithm based on the belief functions theory. Two independent observers
      performed all segmentations twice. Accuracy, intraobserver variability, and
      interobserver variability were evaluated by the Bland-Altman method. The number
      and type of manual corrections were recorded as well as the entire processing
      time. RESULTS: The mean renal volume estimated by fluid displacement was 114 mL
      (range, 38-224 mL). With regard to the renal volumes obtained from assessments of
      adjacent axial MR images, the maximal SDs of the difference were 2.2 mL
      (accuracy), 0.6 mL (intraobserver variability), and 1.8 mL (interobserver
      variability). Segmentation of axial slices provided better accuracy and
      reproducibility than coronal slices. Overlapped coronal slices yielded poor
      results because of the partial volume effect. The mean processing time including
      optional manual modifications was less than 75 seconds. CONCLUSION: The belief
      functions theory can be considered an accurate and reproducible mathematic method
      to assess renal volume from MR adjacent images.

PMID- 18716081
TI  - Applications of SPECT/CT in nuclear radiology.
AB  - OBJECTIVE: The purpose of this pictorial essay is to illustrate several clinical
      situations in which SPECT/CT can be effectively applied in nuclear radiology
      practice. CONCLUSION: SPECT/CT has recently emerged as a valuable adjunct to
      standard techniques in clinical nuclear radiology. This technique provides
      significantly improved scintigraphic localization and characterization of
      disease, increasingly important in this era of minimally invasive surgery and
      targeted radiotherapy.

PMID- 18716082
TI  - LCIS found at core needle biopsy may not need surgical excision.

PMID- 18716083
TI  - Image quality of digital direct flat-panel mammography versus an analog screen
      film technique using a low-contrast phantom.
AB  - OBJECTIVE: The objective of our study was to compare the detectability and
      distinguishability of simulated soft-tissue opacities of 50 variants of an
      anthropomorphic breast phantom in mammograms acquired with a digital direct flat
      panel detector versus an analog system; we also compared the image settings
      "analog film," "digital film," and "digital monitor." MATERIALS AND METHODS: The
      studies were performed on digital (Lorad Selenia) and analog (Mammomat 3)
      mammography systems. Four hundred fifty silicone cubes devised with different
      randomly distributed columns, holes, or both columns and holes (diameter, 3-7 mm;
      height, 0.5-4.0 mm) were used as test bodies. One experimental series was
      performed with a silicone scatter body and one with a silicone and an
      anthropomorphic ground-meat scatter body. All x-rays were obtained at identical
      settings and exposures. Four radiologists rated the films and monitor-displayed
      images independently of each other in randomized order on a standardized
      electronic questionnaire. RESULTS: The digital monitor technique generally scored
      better than digital film viewing and analog readings. The McNemar test for
      multiple paired comparisons mostly yielded a p value of < 0.0005. The smallest
      volume category counted as the most valid test scenario for all raters, where the
      percentage of correct positive findings ranged between 30% and 58% (analog
      technique), 43% and 68% (digital film viewing), and 55% and 66% (monitor
      viewing). The corresponding accuracy rates were 77-93%, 75-95%, and 81-85%,
      respectively, with kappa values of 0.2-0.5 (analog) and 0.3-0.6 (digital) for
      comparing the gold standard with raters' evaluations. CONCLUSION: Digital flat
      panel mammography is superior to the analog screen-film method for the detection
      of simulated opacities.

PMID- 18716084
TI  - Radiologic features of polyacrylamide gel mammoplasty.
AB  - OBJECTIVE: The objective of our study was to describe the imaging features of
      polyacrylamide gel breast implants in women with and those without complications
      from mammoplasty. CONCLUSION: Although polyacrylamide gel implants may mimic
      conventional implants on both sonography and MRI in women who do not have
      complications from mammoplasty, polyacrylamide gel implants have some
      distinguishing features. The imaging appearance of polyacrylamide gel implants is
      related to the technique of injection and whether there are any associated
      complications. The implants are usually in a retroglandular location.
      Mammography, sonography, and MRI can be used to evaluate short-term
      complications, although MRI appears to be the most sensitive. Common short-term
      complications include extravasation of polyacrylamide gel and secondary
      infection, which may be related to lactation. The long-term complications of
      polyacrylamide gel mammoplasty are unknown. Knowledge of the appearances of
      polyacrylamide gel implants in women with and those without complications from
      mammoplasty is useful in the radiologic evaluation of such patients.

PMID- 18716085
TI  - Reliability of non-imaging-guided glenohumeral joint injection through rotator
      interval approach in patients undergoing diagnostic MR arthrography.
AB  - OBJECTIVE: The purpose of our study is to review the accuracy of our method of
      non-imaging-guided anterior glenohumeral gadolinium contrast injection targeting
      the rotator interval in 100 consecutive patients. MATERIALS AND METHODS: One
      hundred consecutive community-referred patients at our MRI facility underwent non
      imaging-guided glenohumeral contrast injection targeting the rotator interval,
      with no patients excluded on the basis of expected diagnosis. The studies were
      then retrospectively reviewed for accuracy of injection based on patient factors
      and diagnosis. RESULTS: This method was 99% accurate in our study, regardless of
      diagnosis. CONCLUSION: The relative ease, efficiency, reproducibility, and
      accuracy of this method of non-imaging-guided anterior glenohumeral injection
      make it the method of choice at our institution, and we believe this technique
      merits consideration for more widespread utilization.

PMID- 18716086
TI  - Radiology in Korea: what is happening?

PMID- 18716087
TI  - Acute pulmonary thromboembolism: a historical perspective.

PMID- 18716088
TI  - Percutaneous abdominal abscess drainage: a historical perspective.

PMID- 18716089
TI  - Cortical morphologic features of axillary lymph nodes as a predictor of
      metastasis in breast cancer: in vitro sonographic study.
AB  - OBJECTIVE: The purpose of this study was in vitro sonographic-pathologic
      correlation of findings in dissected axillary lymph nodes from breast cancer
      patients undergoing axillary lymph node dissection and classification of the
      sonographic appearance of the nodes on the basis of cortical morphologic features
      to facilitate early recognition of metastatic disease. MATERIALS AND METHODS:
      High-resolution sonography was used for in vitro examination of 171 lymph nodes
      from 19 axillae in 18 patients with unknown nodal status who underwent axillary
      lymph node dissection for early infiltrating breast cancer. The images were
      evaluated by two blinded observers, and discordant readings were referred to a
      third blinded observer. Each lymph node was classified as one of types 1-6
      according to cortical morphologic features. Types 1-4 were considered benign,
      ranging from hyperechoic with no visible cortex to thickened generalized
      hypoechoic cortical lobulation. Type 5 (focal hypoechoic cortical lobulation) and
      type 6 (hypoechoic node with absent hilum) nodes were considered metastatic. The
      reference standard for metastatic disease was histopathologic evaluation of
      sectioned nodes by a single pathologist blinded to sonographic findings. Largest
      nodal diameter also was measured. RESULTS: Interobserver agreement was 77% for
      classification of nodal morphology (types 1-6) and 88% for characterization of a
      node as benign or malignant. Sensitivity, specificity, positive predictive value,
      negative predictive value, and overall accuracy of cortical shape in prediction
      of metastatic involvement of axillary nodes were 77%, 80%, 36%, 96%, and 80%.
      Type 4 nodes had the most false-negative findings (four of 36). Node size ranged
      from 0.2 to 3.8 cm, and subcentimeter nodes of all types were detected.
      CONCLUSION: In breast cancer, axillary lymph nodes can be classified according to
      cortical morphologic features. Predominantly hyperechoic nodes (types 1-3) can be
      considered benign. Generalized cortical lobulation (type 4) is uncommonly a false
      negative finding, but metastasis, if present, is invariably detected at sentinel
      node mapping. The presence of asymmetric focal hypoechoic cortical lobulation
      (type 5) or a completely hypoechoic node (type 6) should serve as a guideline for
      universal performance of fine-needle aspiration for preoperative staging of
      breast cancer. This classification, when verified with larger samples, may serve
      as a useful clinical guideline if proven with results of in vivo studies.

PMID- 18716090
TI  - Application of sonographic BI-RADS to synchronous breast nodules detected in
      patients with breast cancer.
AB  - OBJECTIVE: The purpose of this study was to evaluate the applicability of the
      current BI-RADS for sonography to the assessment of synchronous breast nodules
      other than the primary malignant tumor in patients with breast cancer. MATERIALS
      AND METHODS: One hundred eighty-nine synchronous nodules in 147 breast cancer
      patients were surgically excised after localization, and 412 synchronous nodules
      in 191 patients were observed or biopsied or excised without localization. Among
      a total of 601 synchronous nodules, 372 nodules were ipsilateral and 229 were
      contralateral to a primary malignant tumor. Two radiologists retrospectively
      reviewed sonograms of these nodules and determined the sonographic BI-RADS
      category without clinical information or pathologic results. For each nodule, the
      preoperative BI-RADS category and pathologic or follow-up results were compared.
      RESULTS: Four hundred eighty-two nodules were classified category 3; 112 nodules,
      category 4; and seven nodules, category 5. Fifty-five (11.4%) of the category 3
      nodules and 57 (47.9%) of the category 4 and 5 nodules were confirmed malignant.
      Thirty-six (21.2%) of 170 category 3 synchronous nodules in the same quadrant as
      the primary tumor were confirmed malignant, as were 12 (9.8%) of 122 nodules in a
      different quadrant and eight (4.2%) of 190 nodules in the contralateral breast.
      CONCLUSION: For assessment of synchronous nodules in breast cancer patients,
      application of conventional screening sonographic BI-RADS categories may not
      account for possible increased risk of malignancy in synchronous nodules,
      especially those in the same quadrant of the breast as the index malignant tumor.

PMID- 18716091
TI  - Role of breast sonography in imaging of adolescents with palpable solid breast
      masses.
AB  - OBJECTIVE: The purpose of this study was to assess the role of sonography in the
      diagnosis and management of palpable solid breast masses in adolescents and to
      correlate the sonographic findings with the histopathologic findings and clinical
      outcome. MATERIALS AND METHODS: A retrospective study was conducted with the
      breast sonograms of 20 adolescent girls 13-19 years old who presented with
      palpable breast masses found to be solid at breast sonography. The Stavros
      sonographic criteria were used to assess the benignity or malignancy of solid
      breast masses. All sonographic findings were correlated with histopathologic or
      clinical follow-up findings. RESULTS: Sonography showed 21 solid masses in 20
      patients (one patient had bilateral solid breast masses). All but six solid
      masses were presumed benign according to the Stavros sonographic criteria. All
      solid masses were proved benign at histopathologic or clinical follow-up
      examination. CONCLUSION: Sonography was not useful for predicting the histologic
      diagnosis of all solid benign breast masses in adolescent patients. The Stavros
      sonographic criteria, however, were useful for predicting benignity in 65% of the
      breast masses on which histopathologic examination was performed. Tissue biopsy
      may be performed on solid breast masses that do not meet the criteria for benign
      masses according to the Stavros sonographic criteria.

PMID- 18716092
TI  - Efficacy of contrast-enhanced CT in assessing the endometrium.
AB  - OBJECTIVE: The purpose of our study was to determine the efficacy of contrast
      enhanced CT in detecting a thickened endometrium. We used transvaginal sonography
      as the reference standard. MATERIALS AND METHODS: Between March 2005 and January
      2007, data from 259 patients (mean age, 47 years; age range, 18-90 years) who
      underwent transvaginal sonography and contrast-enhanced CT of the pelvis were
      analyzed retrospectively. The endometrium was quantitatively measured in
      millimeters on sonography. On CT it was qualitatively categorized as normal,
      thickened, indeterminate, or not visualized and compared with the sonography
      findings and original radiology reports. When the endometrium was indeterminate
      (thickened or triangular in shape on axial images), sagittal reconstructions were
      performed for final categorization. Two reviewers evaluated the CT scans and
      sonograms jointly with differences resolved by consensus. Kappa, Wilcoxon's rank
      sum test, and intraclass correlation statistics were derived. RESULTS: The
      overall sensitivity and specificity of CT in detecting the thickened endometrium
      was 53.1% and 93.5%, respectively, relative to transvaginal sonography. The
      positive and negative predictive values were 66.7% and 89.1%, respectively.
      Kappa, the statistical measure of agreement between CT and sonography data, was
      0.5049. All cases of a triangular endometrium were normal in size on sagittal
      reconstruction images. CONCLUSION: Routine pelvic CT correctly identifies a
      normal endometrium in most patients. Sagittal reconstruction images are helpful
      to further evaluate the endometrium on CT in cases with a prominent or triangular
      endometrium because these are often related to uterine version. CT is relatively
      insensitive in detecting the thickened endometrium but better able to identify
      gross rather than subtle thickening, which must be further characterized by
      transvaginal sonography.

PMID- 18716093
TI  - MDCT in the preoperative planning of abdominal perforator surgery for
      postmastectomy breast reconstruction.
AB  - OBJECTIVE: This study aimed to evaluate the utility of MDCT in planning abdominal
      perforator surgery for breast reconstruction in patients who have undergone
      mastectomy. SUBJECTS AND METHODS: One hundred twenty-six consecutive patients
      scheduled for postmastectomy breast reconstruction using deep inferior epigastric
      perforator flaps underwent MDCT. The images were evaluated to identify,
      characterize, and map the dominant musculocutaneous perforator vessels of the
      deep inferior epigastric artery. In the first 36 patients, we compared the
      intraoperative findings with the preoperative MDCT findings. In the latter 90
      patients, the dominant perforator vessels were directly selected on the basis of
      MDCT findings. RESULTS: We found an exact correlation between the intraoperative
      and radiologic findings in the first 36 cases. In the following 90 cases, the
      average operating time saved per patient was 1 hour 40 minutes and there was a
      significant reduction in postsurgical complications. The preoperative evaluation
      by MDCT confirmed the wide range of variability in the vascular anatomy of the
      abdominal wall previously described in anatomic studies. CONCLUSION: MDCT
      provides valuable information before surgery about the arterial anatomy of the
      inferior abdominal wall. It enables accurate identification of the most suitable
      dominant perforator vessel and makes surgical perforator flap procedures for
      breast reconstruction faster and safer.

PMID- 18716094
TI  - Evaluation of MRI findings after polyacrylamide gel injection for breast
      augmentation.
AB  - OBJECTIVE: Polyacrylamide gel injection mammoplasty has recently been used for
      breast augmentation. However, many complications have been reported including
      complications that in some patients resulted in the need for mastectomy. This
      article reviews the MRI appearances of various complications of polyacrylamide
      gel injection mammoplasty including breast asymmetry; intramammary or
      extramammary gel displacement, including intrathoracic extension; and glandular
      atrophy, inflammation, and infection resulting in mastectomy. CONCLUSION: Because
      poly acrylamide gel has a high water content, we found that sagittal and axial T2
      weighted are the best sequences to use to detect complications.

PMID- 18716095
TI  - Pure ductal carcinoma in situ: a range of MRI features.
AB  - OBJECTIVE: The purpose of this article is to describe and illustrate the variety
      of common morphologic features, enhancement patterns, and kinetics of pure ductal
      carcinoma in situ (DCIS) on dynamic contrast-enhanced MRI of the breast, using
      the American College of Radiology BI-RADS lexicon. CONCLUSION: Breast MRI plays
      an important role in the detection of DCIS, which most often appears as nonmass
      clumped enhancement, in a ductal or segmental distribution, with variable
      enhancement kinetics.

PMID- 18716096
TI  - Spectrum of papillary lesions of the breast: clinical, imaging, and pathologic
      correlation.
AB  - OBJECTIVE: Papillary lesions of the breast are a heterogeneous group of lesions
      that are difficult to diagnose as benign or malignant. The purpose of this
      article is to review clinical presentation, imaging features, and pathologic
      correlation of papillary lesions of the breast and to discuss the prognosis and
      management of these lesions. CONCLUSION: Recognition of the variety of benign and
      malignant papillary lesions of the breast will facilitate diagnosis and proper
      management.

PMID- 18716097
TI  - MR diskography and CT diskography with gadodiamide-iodinated contrast mixture for
      the diagnosis of foraminal impingement.
AB  - OBJECTIVE: This study was designed to investigate whether the use of MR
      diskography would result in improved reader confidence over the use of CT
      diskography alone for evaluating foraminal impingement causing lumbar
      radiculopathy. SUBJECTS AND METHODS: Sixteen disk levels in 14 consecutive
      patients with suspected foraminal impingement causing lumbar radiculopathy were
      prospectively included in the study. A mixture of diluted gadodiamide and
      iodinated contrast material was injected at each disk level. After diskography, a
      CT scan (CT diskography) and T1-weighted fat-suppressed MR image (MR diskography)
      were obtained. Two spine radiologists and an orthopedic spine surgeon
      independently scored CT diskography and MR diskography for foraminal evaluation
      on a 3-point scale: 1, low confidence; 2, moderate confidence; and 3, high
      confidence. Each reader also assessed whether MR diskography showed an additional
      benefit over CT diskography with regard to the depiction of foraminal
      abnormalities only. Another radiologist reviewed conventional MR images focused
      on disk height and morphology. RESULTS: The reviewers' confidence scores for MR
      diskography were superior to those for CT diskography (reader 1, p = 0.00008;
      reader 2, p = 0.0008; reader 3, p = 0.0015) (p < 0.05). MR diskography was
      considered beneficial in 13 of 16 disk levels (reader 1), 14 of 16 (reader 2),
      and 14 of 16 (reader 3). MR diskography increased the confidence scores for the
      detection of foraminal impingement, especially in cases of severe disk
      degeneration, but did not show additional benefits in cases of an extensive
      vacuum in the disk or large disk extrusion. CONCLUSION: Simultaneous MR
      diskography and CT diskography with a mixture of gadodiamide and iodinated
      contrast material may be beneficial for evaluating foraminal impingement causing
      lumbar radiculopathy.

PMID- 18716098
TI  - Ganglia of the hand and wrist: a sonographic analysis.
AB  - OBJECTIVE: The purpose of this study was to analyze the sonographic appearance of
      a large series of pathologically proven ganglia. MATERIALS AND METHODS: A
      computer search of sonography and pathology reports for hand and wrist ganglia
      was performed. All sonography reports and images were reviewed for ganglion size,
      location, presence of a neck, echogenicity, acoustic enhancement, locules, color
      Doppler flow, margins, wall thickness, and calcifications and to determine if the
      ganglion was palpable or collapsed. All pathology reports were reviewed for
      histologic features that were then correlated with the sonographic images.
      Ganglia were categorized into three groups: simple, complex cystic, and solid
      appearing. RESULTS: Of 60 ganglia, 34 were complex, 91% of which were located
      within the dorsal or volar wrist; 97% had well-defined margins; 76%, locules;
      68%, acoustic enhancement; 47%, a thick wall; 15%, internal reflectors; and 12%,
      blood flow. Of the 23 simple ganglia, 11 involved the extensor or flexor tendon
      sheath, 73% of which were simple. Complex ganglia had a larger mean volume than
      simple. Three ganglia were solid-appearing. A visible neck was seen in 25% of
      ganglia. CONCLUSION: Most ganglia are complex rather than simple on sonography.
      Complex ganglia are larger than simple ganglia; located within the dorsal or
      volar wrist; and usually have well-defined margins, thick walls, locules, and
      acoustic enhancement. A small percentage have blood flow and internal reflectors.
      Simple ganglia are smaller and can occur within the volar or dorsal wrist, or
      flexor tendon sheath. Most flexor tendon sheath ganglia are simple rather than
      complex. Solid-appearing ganglia, although unusual, may mimic a benign neoplasm
      or synovitis.

PMID- 18716099
TI  - In vivo trabecular bone morphologic and mechanical relationship using high
      resolution 3-T MRI.
AB  - OBJECTIVE: The purpose of this study was to investigate the in vivo morphologic
      and elastic parameters of trabecular bone with high-resolution 3-T MRI in a
      healthy reference population. SUBJECTS AND METHODS: A series of wrist MR images
      were acquired with high-spatial-resolution (180 mum) isotropic voxels from 40
      subjects without reported bone disease. After image postprocessing, the bone
      volume-to-total volume ratio, trabecular thickness, trabecular separation, and
      trabecular number were calculated in the morphologic analysis. Trabecular bone
      was mechanically simulated using the finite-element method to calculate the
      apparent elastic modulus parameter. The relationship between morphologic and
      mechanical parameters was studied. The influence of the analyzed bone volume was
      also investigated. RESULTS: Statistically significant sex influences were found
      on the bone volume-to-total volume ratio (p = 0.003), trabecular thickness (p =
      0.02), and apparent elastic modulus (p = 0.01); these parameters were lower in
      women. However, trends were found only on trabecular separation (p = 0.06) and
      trabecular number (p = 0.07). Age had no statistically significant influence in
      any morphologic (bone volume-to-total volume ratio, r = -0.24, p = 0.13;
      trabecular thickness, r = -0.03, p = 0.88; trabecular separation, r = 0.12, p =
      0.47; and trabecular number, r = -0.23, p = 0.16) or elastic (apparent elastic
      modulus, r = -0.18, p = 0.26) parameter. A statistically significant relationship
      between apparent elastic modulus and the square of bone volume-to-total volume
      ratio was found (r = 0.968, p < 0.001). This association was not seen (r = 0.185,
      p = 0.25) and apparent elastic modulus results were considerably different (p <
      0.001) if the volume of analyzed bone was reduced. CONCLUSION: We found that bone
      volume-to-total volume ratio, trabecular thickness, and apparent elastic modulus
      are parameters significantly influenced by sex. Apparent elastic modulus results
      show a relationship with bone volume-to-total volume ratio. Trabecular bone
      volume should be maximized for an appropriate mechanical analysis.

PMID- 18716100
TI  - Osborne-cotterill lesion: an osseous defect of the capitellum associated with
      instability of the elbow.
AB  - OBJECTIVE: Posterolateral rotatory instability of the elbow is a diagnosis
      largely made by clinical examination; no relevant radiographic signs have been
      reported. We have seen four patients with an osseous defect and detachment of a
      fragment of bone in the posterolateral margin of the capitellum. These patients
      had chronic posterolateral rotatory instability of the elbow. CONCLUSION: An
      osseous defect of the posterolateral corner of the capitellum is an uncommon
      finding that in each instance was associated with chronic posterolateral rotatory
      instability of the elbow. We termed this lesion the "Osborne-Cotterill lesion."
      We report our findings in these patients; when this lesion is diagnosed,
      clinicians should consider posterolateral rotatory instability.

PMID- 18716101
TI  - MRI of HAGL lesions: four arthroscopically confirmed cases of false-positive
      diagnosis.
AB  - OBJECTIVE: The purpose of this article is to present the cases of four
      consecutive patients with preoperative MR diagnosis of humeral avulsion of the
      glenohumeral ligament (HAGL) who had no evidence of HAGL at arthroscopy.
      CONCLUSION: These four cases suggest that the diagnosis of HAGL should be
      reserved for arthroscopy and illustrate the difficulty in distinguishing HAGL
      from other abnormalities of the inferior glenohumeral ligament complex with MRI.
      Thus, MRI findings classically associated with HAGL should be more broadly
      described as defects of the inferior glenohumeral ligament complex. This
      terminology more accurately describes the abnormalities of the inferior
      glenohumeral ligament complex that may be depicted by MRI.

PMID- 18716102
TI  - MDCT and 3D imaging in transient enteroenteric intussusception: clinical
      observations and review of the literature.
AB  - OBJECTIVE: This article will review the current role of MDCT and 3D imaging in
      the diagnosis and management of adults with enteroenteric intussusception.
      CONCLUSION: Because of significant advancements in CT along with its increasing
      use, detection of enteroenteric intussusceptions by CT has increased. These
      findings are sometimes in asymptomatic patients, often transient, and without an
      identifiable lead point. This has complicated the management of adult patients
      with intussusception because not every patient with intussusception may need
      surgery.

PMID- 18716103
TI  - Utility of CT whirl sign in guiding management of small-bowel obstruction.
AB  - OBJECTIVE: The purpose of this study was to examine the relation between the CT
      whirl sign and outcome among patients with a clinical and radiologic diagnosis of
      small-bowel obstruction (SBO). MATERIALS AND METHODS: The cases of 453 patients
      who underwent abdominal CT because of clinical suspicion of SBO were reviewed
      retrospectively. Patients with a radiologic diagnosis of SBO were included.
      Management with surgery or medical therapy was correlated with the presence of
      the whirl sign and other radiologic findings. Statistical calculations were
      performed to determine the value of the whirl sign in predicting the type of
      management needed for SBO. RESULTS: According to CT criteria, 194 patients
      received a diagnosis of SBO and were included in the study. The whirl sign was
      identified on the CT scans of 40 of the 194 patients. Thirty-two of the 40
      patients had SBO necessitating surgery, for a positive predictive value of 80%;
      133 of 154 patients did not need surgery, for a negative predictive value of 86%.
      Fifty-three of 194 patients either underwent surgery or died of SBO during
      conservative therapy. The whirl sign was present on the CT scans of 32 of the 53
      patients, for a sensitivity of 60%. One hundred thirty-three of 141 patients did
      not need surgery and did not have a whirl sign, for a specificity of 94%. The
      odds ratio for the whirl sign in predicting the presence of SBO necessitating
      surgery was 25.3 (95% CI, 10.3-62.3). CONCLUSION: A patient with the whirl sign
      on CT is 25.3 times as likely as a patient without the sign to have SBO
      necessitating surgery. The results suggest an important role of the whirl sign in
      assessment of treatment options for patients with clinical and radiologic signs
      of SBO.

PMID- 18716104
TI  - CT of the normal esophagus to define the normal air column and its extent and
      distribution.
AB  - OBJECTIVE: This study was designed to quantify and characterize the air
      containing thoracic esophagus on CT to help diagnose diseases and facilitate
      correlation with lung diseases that may be associated with aspiration. SUBJECTS
      AND METHODS: The maximal air-containing esophageal lumina on each section of
      standard CT scans of 110 subjects were measured. These subjects came from a
      cohort of 10,132 self-reported healthy individuals who underwent CT for
      measurement of coronary artery calcium. Measurements were interpolated to account
      for variation in the length of the thoraces. RESULTS: Greater than 60% of the
      esophageal segments contained no air. On average the maximum air column was 10.5
      (SD, 5.0) mm. Only 7.9% of the lumina were > 10 mm. Only 2% were > 15 mm, and
      only 0.2% were > 20 mm. The average number of lumina > 10 mm as a proportion of
      the entire esophageal length was 8% (14%). The average size at the carina was 2.6
      (4.1) mm. In the upper 30% and from 61% to 75% down the length of the esophagus,
      < 5% of the lumina were > 10 mm. Less than 3% of subjects had air in the lowest
      two sections, indicating that the normal lower esophageal sphincter was closed.
      CONCLUSION: Esophageal air of > 10 mm should be considered abnormal in all
      segments except between the cardiac ventricles and lower esophageal sphincter. In
      this area, > 15 mm should be considered abnormal. An air-fluid level is abnormal.

PMID- 18716105
TI  - Tumor staging of advanced esophageal cancer: combination of double-contrast
      esophagography and contrast-enhanced CT.
AB  - OBJECTIVE: The objective of this study was to compare the diagnostic accuracy of
      tumor staging in patients with advanced esophageal cancer based on contrast
      enhanced CT findings alone with that based on a combination of CT and double
      contrast esophagography and to evaluate the relevance of tumor stage to survival
      rate. MATERIALS AND METHODS: In 94 patients who underwent surgery as the primary
      treatment for esophageal cancer and had a diagnosis of postoperative T stage 3
      (pT3) or pT4 disease based on pathologic examination, T stage was evaluated using
      CT alone and using a combination of CT and double-contrast esophagography. The
      diagnostic criterion for T4 disease using CT alone was tumor strongly displacing
      or deforming adjacent organs. The diagnostic criterion for T4 disease using the
      combined method was tumor displacing or deforming adjacent organs in the
      direction that corresponded to the direction of the location of the tumor or the
      deepest ulcer as diagnosed by barium esophagography. Concordance of T staging
      based on imaging with postoperative T staging based on pathology results, the
      gold standard, and survival rate were assessed for CT alone and for the combined
      method. RESULTS: The concordance rate with postoperative T staging pathology
      results was 78% for CT alone and 84% for CT and double-contrast esophagography
      combined, with a significant difference between the two diagnostic methods. For
      patients with a diagnosis of T3 and those with a diagnosis of T4 using CT alone,
      the 3-year survival rate was 42% and 26%, respectively, with no significant
      difference between the two. For patients with a diagnosis of T3 and those with a
      diagnosis of T4 using the combined method, the 3-year survival rate was 42% and
      21%, respectively, with a significant difference between the two. CONCLUSION: The
      diagnostic performance of contrast-enhanced CT and double-contrast esophagography
      combined in staging advanced esophageal tumors is better than that of CT alone
      and thus has potential for estimating prognosis.

PMID- 18716106
TI  - Diffuse esophageal spasm: CT findings in seven patients.
AB  - OBJECTIVE: The purpose of this study was to determine the frequency and
      appearance of esophageal wall thickening on CT scans in a series of patients with
      findings of diffuse esophageal spasm on barium studies. CONCLUSION: CT revealed
      marked esophageal wall thickening in seven (21%) of 33 patients who had findings
      of diffuse esophageal spasm on barium studies. CT showed significantly greater
      esophageal wall thickening in the lower thoracic esophagus 5 cm above the
      gastroesophageal junction than in the upper thoracic esophagus at the level of
      the aortic arch or in the midthoracic esophagus at the level of the carina (p <
      0.01). This esophageal wall thickening corresponded to the presence of multiple
      strong nonperistaltic contractions in the lower thoracic esophagus on barium
      studies. Our findings suggest that diffuse esophageal spasm should be included in
      the differential diagnosis when CT shows smooth circumferential wall thickening
      in the lower half of the thoracic esophagus, particularly in elderly patients
      with dysphagia or chest pain.

PMID- 18716107
TI  - Analysis of enhancement pattern of flat gallbladder wall thickening on MDCT to
      differentiate gallbladder cancer from cholecystitis.
AB  - OBJECTIVE: The objective of our study was to determine the diagnostic value of
      analyzing the pattern of gallbladder wall enhancement on MDCT to characterize
      diffuse gallbladder wall thickening as benign or malignant. MATERIALS AND
      METHODS: MDCT scans obtained during the portal venous phase in 78 patients with
      gallbladder wall thickening caused by various pathologic conditions were
      retrospectively reviewed by two blinded observers. The CT features of benign and
      malignant gallbladder wall thickening were compared by means of univariate and
      multivariate analyses. The study cases were then divided into five patterns
      according to enhancement pattern. Using these five patterns, two radiologists
      reviewed the MDCT images and recorded their diagnostic confidence for
      differentiating benign versus malignant cause on a 5-point scale. The diagnostic
      performance of CT was evaluated by each observer using a receiver operating
      characteristic curve analysis. RESULTS: The thicknesses of the inner and outer
      layers ("thick" enhancing inner layer > or = 2.6 mm, "thin" outer layer < or =
      3.4 mm), strong enhancement of the inner wall, and irregular contour of the
      affected wall were significant predictors for a malignant cause of gallbladder
      wall thickening (p < 0.001). The two-layer pattern with a strongly enhancing
      thick inner layer and weakly enhancing or nonenhancing outer layer and the one
      layer pattern with a heterogeneously enhancing thick layer were patterns that
      were significantly associated with gallbladder cancer (p < 0.05). When we
      consider those two enhancing patterns as a sign of malignancy, the diagnostic
      accuracy of MDCT was 89.1% and 87.6% for the two observers, respectively.
      CONCLUSION: Analyzing the enhancement pattern of a thickened gallbladder wall on
      MDCT is helpful in differentiating gallbladder cancer from benign inflammatory
      diseases.

PMID- 18716108
TI  - Optimal arterial phase imaging for detection of hypervascular hepatocellular
      carcinoma determined by continuous image capture on 16-MDCT.
AB  - OBJECTIVE: The purpose of this study is to estimate the optimal time delay before
      the initiation of arterial phase scanning for detection of hypervascular
      hepatocellular carcinoma (HCC) on 16-MDCT when a rapid bolus injection of
      contrast medium is administered. SUBJECTS AND METHODS: In this prospective study,
      25 patients (19 men and six women; mean age, 63.5 years; age range, 50-81 years)
      with pathologically confirmed HCC were included. Dynamic 16-MDCT imaging was
      performed in cine mode using 70 mL of nonionic iodinated contrast medium (300 mg
      I/mL) at an injection rate of 7 mL/s. Four consecutive 5-mm-thick slices at the
      maximum diameter of the HCC were selected as the region of interest. Time
      attenuation curves were generated by region of interest drawn on the aorta,
      tumor, and liver. Qualitative assessments of conspicuity for contrast medium wash
      in, peak, and wash-out of aorta and tumor were performed. RESULTS: There were 108
      arterial phase enhancing lesions (mean [+/-SD], 4.9 +/- 2.4 cm; range, 0.7-12.9
      cm) in the 25 patients. The maximum Hounsfield value of aorta, tumor, and
      background liver parenchyma were 463.8 +/- 98 HU, 106.5 +/- 19 HU, and 98.3 +/-
      14 HU, respectively. At the time of onset of peak tumor enhancement, the
      difference between tumor density and background liver density was 38.2 +/- 19 HU.
      The time-attenuation curve showed that the mean times of contrast enhancement
      start, peak, and end were 9.2 +/- 2.7 seconds, 19.4 +/- 2.1 seconds, and 38 +/-
      13.5 seconds, respectively, for the aorta, and 15.5 +/- 2.6 seconds, 26.3 +/- 2.9
      seconds, and 57.7 +/- 14.4 seconds, respectively, for 25 pathologically confirmed
      hepatocellular carcinomas. Qualitatively, the mean times of contrast enhancement
      wash-in, peak, and washout were 10.2 +/- 2.8 seconds, 19.9 +/- 3 seconds, and
      39.9 +/- 9.2 seconds, respectively for the aorta, and 18 +/- 4.2 seconds, 27 +/-
      3 seconds, and 55.7 +/- 21 seconds, respectively, for tumor. There were no
      differences between quantitative and qualitative measurements of wash-in and peak
      time for the aorta (p = 0.00017, p = 0.00016) and tumor (p = 0.00163, p =
      0.00040). CONCLUSION: When using 70 mL of 300 mg I/mL of contrast medium with an
      injection rate of 7 mL/s in 16-MDCT scanning, the optimal time to initiate
      scanning for HCC is 26.3 +/- 2.9 seconds (range, 24.0-34.5 seconds) after
      contrast medium administration.

PMID- 18716109
TI  - Biliary intraductal papillary-mucinous neoplasm manifesting only as dilatation of
      the hepatic lobar or segmental bile ducts: imaging features in six patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate the imaging features of
      intrahepatic biliary intraductal papillary-mucinous neoplasm manifesting only as
      dilatation of the lobar or segmental bile ducts without a visible mass to
      determine whether this type of cholangiocarcinoma can be recognized on the basis
      of distinct imaging features. CONCLUSION: Intrahepatic biliary intraductal
      papillary-mucinous neoplasm can spread along the mucosa without forming a mass
      and can produce a large amount of mucin. Severe dilatation of the lobar or
      segmental intrahepatic bile ducts with crowding and severe atrophy of the hepatic
      parenchyma are helpful imaging findings.

PMID- 18716110
TI  - Spectrum of biliary and nonbiliary complications after laparoscopic
      cholecystectomy: radiologic findings.
AB  - OBJECTIVE: The purpose of this article is to illustrate the radiologic features
      of various biliary and nonbiliary complications after laparoscopic
      cholecystectomy. CONCLUSION: Various complications should be considered in
      patients who do not make an uneventful postoperative recovery after laparoscopic
      cholecystectomy. Sonography is the easiest and most noninvasive method for
      screening for such complications. MR cholangiography is most effective in showing
      biliary complications and CT, for the evaluation of nonbiliary complications.
      Endoscopic retrograde cholangiography enables not only detailed biliary
      estimation but also biliary decompression.

PMID- 18716111
TI  - Summation of CT scans during radiofrequency ablation for assessing target lesion
      coverage.
AB  - OBJECTIVE: In radiofrequency ablation of lesions that require probe
      repositioning, distinguishing between treated and untreated regions can be
      difficult. We describe a method of using existing CT equipment to summate images
      of a current probe placement with those of earlier placements or scans of
      transiently enhancing targets. CONCLUSION: Summation of CT scans during
      radiofrequency ablation involving multiple probe placements is feasible and
      results in a better appreciation of probe positioning relative to the target
      lesion.

PMID- 18716112
TI  - Laparoscopic cholecystectomy: postoperative imaging.
AB  - OBJECTIVE: The purpose of this article is to describe the imaging findings after
      laparoscopic cholecystectomy, including the normal postoperative findings and the
      typical appearances of major complications. The relative merits of the imaging
      techniques available are discussed. CONCLUSION: Laparoscopic cholecystectomy is a
      commonly performed surgical procedure and radiologists are often called on to
      identify or rule out postoperative complications. In such cases, the correct
      diagnosis is crucial in optimizing patient management.

PMID- 18716113
TI  - Prevalence of unsuspected pancreatic cysts on MDCT.
AB  - OBJECTIVE: Current generation MDCT technology facilitates identification of
      small, nonenhancing lesions in the pancreas. The objective of this study was to
      determine the prevalence of findings of unsuspected pancreatic cysts on 16-MDCT
      in a population of adult outpatients imaged for disease unrelated to the
      pancreas. MATERIALS AND METHODS: Contrast-enhanced MDCT scans of the abdomen were
      reviewed from 2,832 consecutive examinations to identify pancreatic cysts.
      Patients with a history of pancreatic lesions or predisposing factors for
      pancreatic disease or who were referred for pancreatic CT were excluded. RESULTS:
      A total of 73 patients had pancreatic cysts, representing a prevalence of 2.6 per
      100 patients (95% CI, 2.0-3.2). Cysts ranged in size from 2 to 38 mm (mean, 8.9
      mm) and were solitary in 85% of cases. Analysis of demographic information showed
      a strong correlation between pancreatic cysts and age, with no cysts identified
      among patients under 40 years and a prevalence of 8.7 per 100 (95% CI, 4.6-12.9)
      in individuals from 80 to 89 years. After controlling for age, cysts were more
      common in individuals of the Asian race than all other race categories, with an
      odds ratio of 3.57 (95% CI, 1.05-12.13). There was no difference by sex in the
      prevalence of cysts (p = 0.527); however, cysts were on average 3.6 mm larger (p
      = 0.014) in men than women. CONCLUSION: In this outpatient population, the
      prevalence of unsuspected pancreatic cysts identified on 16-MDCT was 2.6%. Cyst
      presence strongly correlated with increasing age and the Asian race.

PMID- 18716114
TI  - Clinical significance of endoleak detected on follow-up CT after endovascular
      repair of abdominal aortic aneurysm.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical significance of
      endoleaks detected on combined arterial and delayed contrast-enhanced follow-up
      CT examinations of patients who have undergone endovascular aneurysm repair of
      abdominal aortic aneurysm. MATERIALS AND METHODS: One hundred forty-four patients
      underwent periodic follow-up CT examinations 12-72 months after abdominal aortic
      aneurysm repair. The CT protocol consisted of an unenhanced scan and contrast
      enhanced scans in the arterial and 90-second delayed phases. The endoleaks
      detected on dual-phase CT scans were evaluated in association with the outcome
      (therapeutic intervention or endoleak resolution). RESULTS: The 144 patients
      underwent 728 CT examinations with a mean follow-up period of 35.5 +/- 14.5
      months. Fifty endoleaks were detected in 50 (34.7%) of the patients. Eight
      endoleaks were detected in the arterial phase only, eight in the delayed phase
      only, and 34 in both phases. Intervention was performed to manage 16 endoleaks
      detected in both phases. CT showed that three endoleaks were stable (two in the
      arterial phase only and one in both phases) and that 31 had resolved completely
      (six in the arterial phase only, eight in the delayed phase only, and 17 in both
      phases). This finding represents a higher frequency of resolution of endoleaks
      detected in one phase only than in both phases (Fisher's exact test, p = 0.006).
      CONCLUSION: Endoleaks detected only in the delayed phase of CT had resolved
      spontaneously without intervention. Therefore, we can consider eliminating the
      delayed phase of acquisition to minimize radiation exposure.

PMID- 18716115
TI  - Peritoneal mesotheliomas: clinicopathologic features, CT findings, and
      differential diagnosis.
AB  - OBJECTIVE: The objective of our study was to illustrate various CT findings of
      peritoneal mesotheliomas, to review their clinicopathologic features, and to
      discuss the differential diagnoses. CONCLUSION: The clinicopathologic features of
      peritoneal mesotheliomas vary among the subtypes such as malignant mesotheliomas,
      cystic mesotheliomas, and well-differentiated papillary mesotheliomas, and
      accordingly, there is a spectrum of CT appearances.

PMID- 18716116
TI  - Visceral artery aneurysms: evaluation using 3D contrast-enhanced MR angiography.
AB  - OBJECTIVE: Visceral artery aneurysms are uncommon, but they are clinically
      important because of the high incidence of rupture and life-threatening
      hemorrhage. Visceral artery aneurysms in patients with vascular anatomic
      variations are extremely rare, but detecting these variations is significant in
      this setting to determine the best treatment strategy; therefore, a thorough
      assessment of the aneurysm and of the vascular anatomy before treatment is
      paramount. CONCLUSION: Three-dimensional contrast-enhanced MR angiography is a
      noninvasive technique for the diagnosis and display of visceral artery aneurysms.
      It can provide 3D anatomic information that is needed for surgery or
      embolization.

PMID- 18716117
TI  - Pulmonary tuberculosis: up-to-date imaging and management.
AB  - OBJECTIVE: Pulmonary tuberculosis (TB) is a common worldwide infection and a
      medical and social problem causing high mortality and morbidity, especially in
      developing countries. The traditional imaging concept of primary and reactivation
      TB has been recently challenged, and radiologic features depend on the level of
      host immunity rather than the elapsed time after the infection. We aimed to
      elaborate the new concept of the diagnosis and treatment of pulmonary TB, to
      review the characteristic imaging findings of various forms of pulmonary TB, and
      to assess the role of CT in the diagnosis and management of pulmonary TB.
      CONCLUSION: Fast and more accurate TB testing such as bacterial DNA
      fingerprinting and whole-blood interferon-gamma assay has been developed. Miliary
      or disseminated primary pattern or atypical manifestations of pulmonary TB are
      common in patients with impaired immunity. CT plays an important role in the
      detection of TB in patients in whom the chest radiograph is normal or
      inconclusive, in the determination of disease activity, in the detection of
      complication, and in the management of TB by providing a roadmap for surgical
      treatment planning. PET scans using 18F-FDG or 11C-choline can sometimes help
      differentiate tuberculous granuloma from lung malignancy.

PMID- 18716118
TI  - Vibration response imaging technology in healthy subjects.
AB  - OBJECTIVE: The vibration response imaging device that we studied (VRIxp) records
      the intensity and location of lung sounds during a cycle of breathing. The goals
      of this study were to describe the characteristic features and quantitative lung
      data recorded by the VRIxp device from healthy asymptomatic subjects. SUBJECTS
      AND METHODS: Breath sounds (frequency range, 150-250 Hz) recorded from the backs
      of 151 healthy asymptomatic subjects (96 nonsmokers and 55 smokers) by the VRIxp
      device were mapped to create a sequence of 2D images. Three raters interpreted
      and scored the images for predefined static and dynamic features. In addition,
      quantitative lung data were analyzed for characteristic regional distributions.
      RESULTS: The readers of the images had good inter- and intrarater agreement.
      Image development in 93% of the evaluations showed an inspiratory and expiratory
      phase with a progressive and regressive stage that developed bilaterally in a
      vertical and synchronized manner. Characteristic image features of the maximum
      energy frame included a smooth, rounded, uninterrupted contour and a planar
      distribution, area size, and intensity that had right-left symmetry. Quantitative
      lung data expressed as percentages of the total (100%) vibration energy were
      normally distributed with mean values (+/- SD) of 55% +/- 6% for the left lung
      and 45% +/- 6% for the right lung. Most of the subjects with images, quantitative
      lung data, or both lacking these typical features were cigarette smokers or had a
      history of smoking (p < 0.05). CONCLUSION: Breath sounds in healthy asymptomatic
      subjects can be recorded and displayed in a dynamic series of images that have
      predictable and characteristic features recognizable and complemented by
      quantitative lung data. Identification and description of these characteristic
      image features in this study will facilitate future studies of vibration imaging
      in specific pulmonary diseases.

PMID- 18716119
TI  - Surgically corrected congenital heart disease: utility of 64-MDCT.
AB  - OBJECTIVE: The purpose of this article is to review the CT appearance of
      postoperative morphology and complications after surgical correction of
      congenital heart anomalies. CONCLUSION: Echocardiography is typically the initial
      imaging technique used for congenital heart disease; however, some thoracic
      regions are beyond the imaging scope of echocardiography, particularly after
      surgical revision. This article shows, through a series of illustrative cases,
      the usefulness of 64-MDCT in these patients.

PMID- 18716120
TI  - MRI of cardiac sarcoidosis: basal and subepicardial localization of myocardial
      lesions and their effect on left ventricular function.
AB  - OBJECTIVE: The objective of our study was to use MRI to analyze the topographic
      localization of myocardial lesions and their relationship to plasma brain
      natriuretic peptide (BNP) levels and several cardiac function parameters in
      patients with cardiac sarcoidosis. MATERIALS AND METHODS: Delayed contrast
      enhanced MRI was performed in 40 patients with sarcoidosis (11 cardiac, 29
      extracardiac cases). Using a 29-segment model of the left ventricle (LV), the
      extent of myocardial hyperenhancement was visually scored (0 = no
      hyperenhancement, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, 4 = 76-100%
      hyperenhancement) and was compared with plasma BNP level and several parameters
      of cardiac function. RESULTS: Ten of the 11 patients with cardiac sarcoidosis
      showed myocardial hyperenhancement, whereas none of the 29 patients without
      cardiac sarcoidosis did. In patients with cardiac sarcoidosis, hyperenhancement
      was significantly more extensive in basal short axis slices than in apical short
      axis slices (p < 0.0005). Myocardial hyperenhancement was significantly more
      frequent in subepicardial layers than in subendocardial layers. The global extent
      of myocardial hyperenhancement was significantly correlated with plasma BNP
      levels and the LV end-diastolic volume index and was negatively correlated with
      the LV ejection fraction. CONCLUSION: In patients with cardiac sarcoidosis,
      myocardial lesions detected on delayed contrast-enhanced MRI were predominantly
      localized in the basal and subepicardial myocardium. The extent of myocardial
      lesions may be related to LV dysfunction and plasma BNP level in patients with
      cardiac sarcoidosis.

PMID- 18716121
TI  - Emergency cardiac CT for suspected acute coronary syndrome: qualitative and
      quantitative assessment of coronary, pulmonary, and aortic image quality.
AB  - OBJECTIVE: The purpose of this study was to determine whether a dedicated
      coronary CT protocol provides adequate contrast enhancement and artifact-free
      depiction of coronary, pulmonary, and aortic circulation. MATERIALS AND METHODS:
      Dedicated coronary 64-MDCT data sets of 50 patients (27 men; mean age, 54 +/-
      12.4 years) consecutively admitted from the emergency department with suspected
      acute coronary syndrome were analyzed. Two independent observers graded overall
      coronary arterial image quality and qualitative and quantitative contrast
      opacification, motion, and streak artifacts within the pulmonary arteries and
      aorta. RESULTS: Coronary image quality was excellent in 48 patients (96%) and
      moderate in two patients (4%). Eleven left main and 22 left upper lobar pulmonary
      arteries were not visualized. Qualitative evaluation showed pulmonary arterial
      tree opacification to be excellent except for the right and left lower lateral
      and posterior segmental branches (52-54% rate of poor opacification).
      Quantitative evaluation showed four central (8%), six lobar (8%), and 206
      segmental (29%) branches had poor contrast opacification (< 200 HU). Nineteen
      right upper lobar arteries (38%) were slightly and one was severely affected by
      streak artifact. At the segmental pulmonary artery level, marked differences in
      contrast enhancement were detected between the upper (292 +/- 72 HU) and both the
      middle (249 +/- 85 HU) and the lower lobes (248 +/- 76 HU) (p < 0.01). Mean
      aortic opacification was 300 +/- 34 HU with excellent contrast homogeneity
      without severe motion or streak artifacts. CONCLUSION: In the evaluation of
      patients presenting to the emergency department with suspected acute coronary
      syndrome, a dedicated coronary CT protocol enables excellent assessment of the
      coronary arteries and proximal ascending aorta but does not depict the pulmonary
      vasculature well enough for exclusion of pulmonary embolism.

PMID- 18716122
TI  - Pulmonary nodules detected at cardiac CT: comparison of images in limited and
      full fields of view.
AB  - OBJECTIVE: The purpose of this study was to compare the frequency of detection of
      pulmonary nodules on cardiac CT scans acquired with a limited field of view with
      the frequency of detection at full field of view. CONCLUSION: Viewing of cardiac
      CT scans obtained only at a limited field of view can result in missing more than
      67% of nodules larger than 1 cm and more than 80% of nodules smaller than 1 cm.

PMID- 18716123
TI  - Incidental findings on cardiac imaging.

PMID- 18716124
TI  - Venous thromboembolism and occult malignancy: simultaneous detection during
      pulmonary CT angiography with CT venography.
AB  - OBJECTIVE: We explored the potential for patients with proven venous
      thromboembolism or pulmonary embolism (PE) to have occult malignancies detected
      during the same CT examination. To verify this, we compared the presence of
      occult malignancies identified on pulmonary artery CT angiography (CTA) and CT
      venography (CTV) when venous thromboembolism (VTE) was present. SUBJECTS AND
      METHODS: Pulmonary artery CTA combined with CTV was performed on a 16-MDCT
      scanner on 186 adult patients suspected of having pulmonary embolism without any
      known malignancies. CTV was performed from the diaphragm to the knee 180 seconds
      after CTA. Two radiologists evaluated the presence of VTE, that is PE or deep
      venous thrombosis (DVT), and tumor lesions on both examinations in consensus. The
      malignant nature of the possibly identified tumors was confirmed by pathologic
      examination. RESULTS: VTE was found in 49 patients (26%). Malignant tumors were
      detected in 24 patients (13%). Eleven patients with malignant tumors had VTE (46%
      of patients with malignant tumors; 22% with VTE and 6% of all patients). There
      was correlation with presence of malignancies between both and DVT and DVT
      associated with PE but not between presence of malignancies and PE only. Patients
      with DVT and those with DVT associated with PE had a risk ratio of 3.2 and 3.3,
      respectively, for having a malignant tumor discovered simultaneously. CONCLUSION:
      A high number of malignant tumors can be incidentally discovered on pulmonary
      artery CTA, even more so with additional CTV. Radiologists should scrutinize
      scans to pick up unknown malignancies, especially in patients with identified
      VTE.

PMID- 18716125
TI  - Qualitative comparison of 3-T and 1.5-T MRI in the evaluation of epilepsy.
AB  - OBJECTIVE: MRI at 3 T, which has a higher signal-to-noise ratio than 1.5-T MRI,
      is potentially more sensitive and specific at delineating epileptogenic lesions
      and may influence management of refractory epilepsy. The purposes of the current
      study were to compare image quality of 3-T MRI with that of 1.5-T MRI in the
      evaluation of epilepsy and, in cases of focal epilepsy, to compare the two field
      strengths in terms of lesion detection and characterization. MATERIALS AND
      METHODS: Retrospective review was performed on 50 sets of MR images of 25
      patients who underwent both 3-T and 1.5-T brain imaging with a dedicated epilepsy
      protocol, including fast spin-echo T2-weighted, coronal FLAIR, coronal fast
      multiplanar inversion recovery, and 3D spoiled gradient-recalled echo pulse
      sequences. Parameters assessed were distortion and artifact, lesion conspicuity,
      gray-white matter differentiation, and motion. Each pulse sequence was graded on
      a 4-point scale. Reviewers performed qualitative assessments of the site of
      abnormality and the most likely diagnosis. RESULTS: MRI at 3 T outperformed MRI
      at 1.5 T in all four parameters and was statistically superior (p < 0.05) to 1.5
      T MRI in all categories except motion. On 3-T MRI, lesions were detected in 65 of
      74 cases compared with 55 of 74 cases at 1.5 T (p = 0.0364), and lesions were
      accurately characterized in 63 of 74 cases compared with 51 of 74 cases at 1.5 T
      (p = 0.0194). The odds ratios showed identification of a focal epileptogenic
      lesion with 3-T MRI 2.57 times as likely as identification with 1.5-T MRI and
      accurate characterization of lesions 2.66 times as likely as characterization
      with 1.5-T MRI. CONCLUSION: In evaluation of epilepsy, MRI at 3 T performed
      better than 1.5-T MRI in image quality, detection of structural lesions, and
      characterization of lesions. High-field-strength imaging should be considered for
      patients with intractable epilepsy and normal or equivocal findings on 1.5-T MRI.

PMID- 18716126
TI  - Imaging of the brachiocephalic vein.
AB  - OBJECTIVE: The purpose of this study was to review the imaging features of
      congenital variants of and pathologic conditions affecting the brachiocephalic
      vein. CONCLUSION: CT and MRI are excellent for visualizing developmental
      anomalies and mediastinal tumors that involve the brachiocephalic vein. Although
      they affect this vein less commonly than do developmental anomalies and tumors,
      trauma, aneurysm formation, stenosis related to dialysis or other conditions, and
      various complications related to central venous catheters do occur, and
      familiarity with the imaging findings is helpful for diagnosis.

PMID- 18716127
TI  - Primary hyperparathyroidism: is there an increased prevalence of renal stone
      disease?
AB  - OBJECTIVE: Parathyroid adenomas cause hypercalcemia and are culprits in the
      development of renal stone disease. With serum assays available, early detection
      of parathyroid tumors is possible. We performed this retrospective review to
      determine whether the prevalence of nephrocalcinosis and nephrolithiasis is still
      increased in patients with primary hyperparathyroidism compared with those not
      affected by the disorder in view of the early detection of parathyroid adenomas.
      MATERIALS AND METHODS: We retrospectively reviewed the renal sonograms of 271
      patients with surgically proven primary hyperparathyroidism. All patients had
      undergone renal imaging within 6 months before parathyroid surgery. Our control
      group consisted of 500 age-matched subjects who had right upper quadrant
      sonograms obtained for various reasons. RESULTS: Nineteen (7.0%) of the 271
      patients with primary hyperparathyroidism had renal stones, and eight (1.6%) of
      the 500 subjects in the control group had stones. Pearson's chi-square analysis
      showed that this difference in prevalence is significant (p < 0.0001).
      CONCLUSION: Our results showed a fourfold increased prevalence of asymptomatic
      renal stone disease in patients with surgically proven primary
      hyperparathyroidism compared with subjects not affected by the disorder. The
      National Institutes of Health consensus conference on asymptomatic primary
      hyperparathyroidism recommended that patients with renal stone disease undergo
      parathyroid surgery. These patients should undergo surgery even if they have
      minimal or no elevation of the total serum calcium value and no other metabolic
      manifestations of hyperparathyroidism. The finding of nephrocalcinosis or
      nephrolithiasis is, therefore, a significant finding in evaluating patients for
      parathyroid surgery. Routine imaging of the kidneys is necessary when primary
      hyperparathyroidism is documented.

PMID- 18716128
TI  - Diagnostic value of high-resolution CT in the evaluation of chronic infiltrative
      lung disease in children.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of CT in the
      diagnosis of chronic infiltrative lung disease in children. MATERIALS AND
      METHODS: Fifty-nine patients selected over a 14-year period (29 girls, 30 boys;
      mean age, 6 +/- 4.9 years; range, 2 months-18 years) had nine disorders. CT scans
      were evaluated independently by two experienced chest radiologists, who were
      unaware of pathologic or clinical data. The radiologists recorded specific CT
      findings of infiltrative lung disease and were asked to give the most likely
      diagnosis and up to two differential diagnoses. Descriptive statistic analysis
      was followed by logistic regression analysis for each elementary lesion on the
      grid of abnormalities. RESULTS: A correct first-choice diagnosis was made in 38%
      of CT observations. The correct diagnosis was among the three main choices in 59%
      of CT observations. Pulmonary alveolar proteinosis (n = 18) was most frequently
      correctly diagnosed; it was the first-choice diagnosis 47% of the time and among
      the three main choices 72% of the time. The correct first-choice diagnosis of
      idiopathic pulmonary fibrosis (n = 16) was made 43% of the time; of
      hypersensitivity pneumonitis (n = 4), 37% of the time; of sarcoidosis (n = 7),
      28% of the time; of idiopathic pulmonary hemosiderosis (n = 6), 16% of the time;
      and of connective tissue diseases (n = 5), 10% of the time. All single cases of
      pulmonary fibrosis with calcification, lymphangiectasia, and Langerhans' cell
      histiocytosis were correctly diagnosed. CONCLUSION: Our results showed there are
      limitations to diagnosing chronic infiltrative lung disease in children on the
      basis of CT data alone. We suppose that these differences are explained by the
      technical difficulties of high-resolution CT in children, the insufficient number
      of cases of and data on high-resolution CT of children, and the heterogeneity of
      lesions of a given cause.

PMID- 18716129
TI  - Marginal zone B-cell non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue
      type: imaging findings.
AB  - OBJECTIVE: The aim of this essay is to describe the imaging features of marginal
      zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type
      throughout various organs. CONCLUSION: Awareness of the expected locations of
      MALT lymphoma combined with knowledge of the incidence and imaging findings leads
      to accurate diagnosis of lesions suspicious for this disorder and helps to
      differentiate this disease from other abnormalities.

PMID- 18716130
TI  - Intraarticular factor IX protein or gene replacement protects against development
      of hemophilic synovitis in the absence of circulating factor IX.
AB  - Hemophilic bleeding into joints causes synovial and microvascular proliferation
      and inflammation (hemophilic synovitis) that contribute to end-stage joint
      degeneration (hemophilic arthropathy), the major morbidity of hemophilia. New
      therapies are needed for joint deterioration that progresses despite standard
      intravenous (IV) clotting factor replacement. To test whether factor IX within
      the joint space can protect joints from hemophilic synovitis, we established a
      hemophilia B mouse model of synovitis. Factor IX knockout (FIX(-/-)) mice
      received a puncture of the knee joint capsule with a needle to induce
      hemarthrosis; human factor IX (hFIX) was either injected through the needle into
      the joint space (intraarticularly) or immediately delivered IV. FIX(-/-) mice
      receiving intraarticular FIX protein were protected from synovitis compared with
      mice receiving same or greater doses of hFIX IV. Next, adeno-associated virus
      (AAV) gene transfer vectors expressing hFIX were injected into knee joints of
      FIX(-/-) mice. Joints treated with 10(10) vector genomes (vg)/joint AAV2-, AAV5-,
      or AAV8-hFIX or 2.5 x 10(9) vg/joint AAV5-hFIX developed significantly fewer
      pathologic changes 2 weeks after injury compared with the pathology of control
      injured contralateral hind limbs. Extravascular factor activity and joint
      directed gene transfer may ameliorate hemophilic joint destruction, even in the
      absence of circulating FIX.

PMID- 18716131
TI  - Tumor necrosis factor SNP haplotypes are associated with iron deficiency anemia
      in West African children.
AB  - Plasma levels of tumor necrosis factor-alpha (TNF-alpha) are significantly raised
      in malaria infection and TNF-alpha is thought to inhibit intestinal iron
      absorption and macrophage iron release. This study investigated putative
      functional single nucleotide polymorphisms (SNPs) and haplotypes across the major
      histocompatibility complex (MHC) class III region, including TNF and its
      immediate neighbors nuclear factor of kappa light polypeptide gene enhancer in B
      cells (lkappaBL), inhibitor-like 1 and lymphotoxin alpha (LTA), in relation to
      nutritional iron status and anemia, in a cohort of 780 children across a malaria
      season. The prevalence of iron deficiency anemia (IDA) increased over the malaria
      season (P < .001). The TNF(-308) AA genotype was associated with an increased
      risk of iron deficiency (adjusted OR 8.1; P = .001) and IDA (adjusted OR 5.1; P =
      .01) at the end of the malaria season. No genotypes were associated with IDA
      before the malaria season. Thus, TNF appears to be a risk factor for iron
      deficiency and IDA in children in a malaria-endemic environment and this is
      likely to be due to a TNF-alpha-induced block in iron absorption.

PMID- 18716132
TI  - PTP1B is a negative regulator of interleukin 4-induced STAT6 signaling.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed enzyme shown
      to negatively regulate multiple tyrosine phosphorylation-dependent signaling
      pathways. PTP1B can modulate cytokine signaling pathways by dephosphorylating
      JAK2, TYK2, and STAT5a/b. Herein, we report that phosphorylated STAT6 may serve
      as a cytoplasmic substrate for PTP1B. Overexpression of PTP1B led to STAT6
      dephosphorylation and the suppression of STAT6 transcriptional activity, whereas
      PTP1B knockdown or deficiency augmented IL-4-induced STAT6 signaling.
      Pretreatment of these cells with the PTK inhibitor staurosporine led to sustained
      STAT6 phosphorylation consistent with STAT6 serving as a direct substrate of
      PTP1B. Furthermore, PTP1B-D181A "substrate-trapping" mutants formed stable
      complexes with phosphorylated STAT6 in a cellular context and endogenous PTP1B
      and STAT6 interacted in an interleukin 4 (IL-4)-inducible manner. We delineate a
      new negative regulatory loop of IL-4-JAK-STAT6 signaling. We demonstrate that IL
      4 induces PTP1B mRNA expression in a phosphatidylinositol 3-kinase-dependent
      manner and enhances PTP1B protein stability to suppress IL-4-induced STAT6
      signaling. Finally, we show that PTP1B expression may be preferentially elevated
      in activated B cell-like diffuse large B-cell lymphomas. These observations
      identify a novel regulatory loop for the regulation of IL-4-induced STAT6
      signaling that may have important implications in both neoplastic and
      inflammatory processes.

PMID- 18716133
TI  - An 86-probe-set gene-expression signature predicts survival in cytogenetically
      normal acute myeloid leukemia.
AB  - Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show
      heterogeneous treatment outcomes. We used gene-expression profiling to develop a
      gene signature that predicts overall survival (OS) in CN-AML. Based on data from
      163 patients treated in the German AMLCG 1999 trial and analyzed on
      oligonucleotide microarrays, we used supervised principal component analysis to
      identify 86 probe sets (representing 66 different genes), which correlated with
      OS, and defined a prognostic score based on this signature. When applied to an
      independent cohort of 79 CN-AML patients, this continuous score remained a
      significant predictor for OS (hazard ratio [HR], 1.85; P = .002), event-free
      survival (HR = 1.73; P = .001), and relapse-free survival (HR = 1.76; P = .025).
      It kept its prognostic value in multivariate analyses adjusting for age, FLT3
      ITD, and NPM1 status. In a validation cohort of 64 CN-AML patients treated on
      CALGB study 9621, the score also predicted OS (HR = 4.11; P < .001), event-free
      survival (HR = 2.90; P < .001), and relapse-free survival (HR = 3.14, P < .001)
      and retained its significance in a multivariate model for OS. In summary, we
      present a novel gene-expression signature that offers additional prognostic
      information for patients with CN-AML.

PMID- 18716134
TI  - European LeukemiaNet criteria for failure or suboptimal response reliably
      identify patients with CML in early chronic phase treated with imatinib whose
      eventual outcome is poor.
AB  - The majority of patients with chronic myeloid leukemia in chronic phase gain
      substantial benefit from imatinib but some fail to respond or lose their initial
      response. In 2006, the European LeukemiaNet published recommendations designed to
      help identify patients responding poorly to imatinib. Patients were evaluated at
      3, 6, 12, and 18 months and some were classified as "failure" or "suboptimal
      responders." We analyzed outcomes for 224 patients with chronic myeloid leukemia
      in chronic phase treated in a single institution to validate these
      recommendations. Patients were followed for a median of 46.1 months. At each time
      point, patients classified as "failure" showed significantly worse survival,
      progression-free survival, and cytogenetic response than other patients; for
      example, based on the assessment at 12 months, the 5-year survival was 87.1%
      versus 95.1% (P = .02), progression-free survival 76.% versus 90% (P = .002), and
      complete cytogenetic response rate 26.7% versus 94.1% (P < .001). Similarly, the
      criteria for "suboptimal response" at 6 and 12 months identified patients
      destined to fare badly, although criteria at 18 months were less useful. The
      predictive value of some other individual criteria varied. In general, the
      LeukemiaNet criteria have useful predictive value, but a case could now be made
      for combining the categories "failure" and "suboptimal response."

PMID- 18716135
TI  - Abnormal number of fetal ribs on 3-dimensional ultrasonography: associated
      anomalies and outcomes in 75 fetuses.
AB  - OBJECTIVE: The purpose of this study was to describe the clinical importance of
      an abnormal number of fetal ribs. METHODS: A retrospective study of all fetuses
      that were found to have an abnormal number of ribs during routine
      ultrasonographic examinations was performed. Volume data sets of the fetal ribs
      were acquired by either static 3- or 4-dimensional volume contrast imaging in
      plane C. In all cases, a meticulous survey of the fetal anatomy was performed,
      and prenatal and postnatal records were reviewed. RESULTS: Seventy-five fetuses
      were found retrospectively to have an abnormal number of ribs. Ultrasonographic
      examinations were done between 14 and 31 weeks' gestation (mean, 21.8 weeks;
      median, 23 weeks). More than 24 ribs were found in 28 fetuses (37%), and fewer
      than 24 ribs were found in 47 (63%). Additional anomalies were found in 22
      fetuses (29%). Cardiovascular anomalies were detected in 10 fetuses. Seven
      fetuses had renal anomalies. Two fetuses had mild ventriculomegaly, and 1 fetus
      had holoprosencephaly. Lung dysplasia was found in 2 cases. One fetus had
      enlarged nuchal translucency with wormian bones. Termination of pregnancy was
      performed in 3 cases because of major malformations. The other 19 fetuses with
      associated abnormalities and the 53 without associated anomalies were born alive
      with only minor anomalies. CONCLUSIONS: An abnormal number of fetal ribs is an
      isolated finding in most cases. It may also be seen with major anomalies;
      however, more frequently the anomalies are minor, and the overall prognosis is
      good.

PMID- 18716136
TI  - Prenatal diagnosis of placenta accreta: sonography or magnetic resonance imaging?
AB  - OBJECTIVE: The purpose of this study was to compare the accuracy of
      transabdominal sonography and magnetic resonance imaging (MRI) for prenatal
      diagnosis of placenta accreta. METHODS: A historical cohort study was undertaken
      at 3 institutions identifying women at risk for placenta accreta who had
      undergone both sonography and MRI prenatally. Sonographic and MRI findings were
      compared with the final diagnosis as determined at delivery and by pathologic
      examination. RESULTS: Thirty-two patients who had both sonography and MRI
      prenatally to evaluate for placenta accreta were identified. Of these, 15 had
      confirmation of placenta accreta at delivery. Sonography correctly identified the
      presence of placenta accreta in 14 of 15 patients (93% sensitivity; 95%
      confidence interval [CI], 80%-100%) and the absence of placenta accreta in 12 of
      17 patients (71% specificity; 95% CI, 49%-93%). Magnetic resonance imaging
      correctly identified the presence of placenta accreta in 12 of 15 patients (80%
      sensitivity; 95% CI, 60%-100%) and the absence of placenta accreta in 11 of 17
      patients (65% specificity; 95% CI, 42%-88%). In 7 of 32 cases, sonography and MRI
      had discordant diagnoses: sonography was correct in 5 cases, and MRI was correct
      in 2. There was no statistical difference in sensitivity (P = .25) or specificity
      (P = .5) between sonography and MRI. CONCLUSIONS: Both sonography and MRI have
      fairly good sensitivity for prenatal diagnosis of placenta accreta; however,
      specificity does not appear to be as good as reported in other studies. In the
      case of inconclusive findings with one imaging modality, the other modality may
      be useful for clarifying the diagnosis.

PMID- 18716137
TI  - Ductus venosus S-wave/isovolumetric A-wave (SIA) index and A-wave reversed flow
      in severely premature growth-restricted fetuses.
AB  - OBJECTIVE: Ductus venosus (DV) Doppler waveforms show 2 periods of decreased
      velocity during iso-volumetric relaxation (isovolumetric relaxation velocity
      [IRV]) and atrial contraction (A wave or end-diastolic velocity [EDV]). In
      intrauterine growth-restricted (IUGR) fetuses, both may become abnormal. The
      hypothesis for this study was that in severely premature IUGR fetuses, Doppler
      assessment of both the IRV and EDV allows a more accurate prediction of fetal
      outcome than absent/reversed end-diastolic flow (A/REDF) alone. METHODS: Ductus
      venosus Doppler waveforms were serially studied in 49 severely premature IUGR
      fetuses from diagnosis until death or delivery. The DV waveforms were assessed
      for peak systolic velocity (PSV), IRV, and EDV and qualitatively for forward end
      diastolic flow or A/REDF. The S-wave/isovolumetric A-wave (SIA) index [PSV/(IRV +
      EDV)] for each fetus was compared to fetal/neonatal outcomes. RESULTS: There were
      8 cases of fetal death (FD), 9 cases of neonatal death (ND), and 32 cases of
      neonatal survival (NS). A receiver operating characteristic (ROC) curve for the
      SIA index in all cases showed that values less than -1.25 correlated with FD and
      those greater than -1.25 correlated with live birth, with 100% sensitivity and
      100% specificity. A second ROC curve of live births showed that values less than
      2.07 correlated with NS and those greater than 2.07 correlated with ND with 67%
      sensitivity and 94% specificity. Ductus venosus A/REDF correlated with FD, ND,
      and NS with sensitivity values of 88%, 78%, and 32%, respectively. Of the 32 NSs,
      11 (34%) had A/REDF with a median of 11 days before delivery. CONCLUSIONS: The
      SIA index is a novel Doppler parameter for assessment of severely premature IUGR
      fetuses that allows a much more accurate prediction of fetal outcome compared to
      A/REDF alone.

PMID- 18716138
TI  - Evaluation of referral indications for fetal echocardiography in Beijing.
AB  - OBJECTIVES: This study was conducted to evaluate the referral indications for
      fetal echocardiography (FE) in a tertiary center and to determine which
      indications were significantly associated with prenatal detection of congenital
      heart disease (CHD). METHODS: The medical records of 1425 consecutive women who
      underwent second- and third-trimester FE at the Ultrasound Center of Beijing
      Obstetrics and Gynecology Hospital from March 2003 to December 2007 were
      reviewed. Referral indications, FE diagnoses, and pregnancy outcomes were
      collected. Univariate and multivariate logistic regression analyses were
      performed to identify those referral indications associated with prenatal
      detection of CHD. RESULTS: In 126 patients (8.8%), CHD was detected prenatally
      and confirmed postnatally. Logistic regression analysis showed that abnormal
      cardiac views and extracardiac malformation findings (especially a single
      umbilical artery) on second-trimester ultrasound screening were found to have
      significantly more CHD (P < .001). The adjusted odds ratios were 15.2 (95%
      confidence interval, 9.85-23.45) and 6.78 (95% confidence interval, 2.38-19.27),
      respectively. CONCLUSIONS: Abnormal cardiac views and extracardiac malformation
      findings on second-trimester ultrasound screening were significantly associated
      with prenatal detection of CHD.

PMID- 18716139
TI  - Nomograms of the axial transverse diameter of the fetal foramen magnum between 14
      and 40 weeks' gestation.
AB  - OBJECTIVE: The purpose of this study was to create reference range nomograms of
      the axial transverse diameter of the fetal foramen magnum (TDFM) between 14 and
      40 weeks' gestation. METHODS: This cross-sectional study included pregnant
      patients between 14 and 41 weeks' gestation. Inclusion criteria consisted of well
      established dates (confirmed by early sonography) and nonanomalous singleton
      fetuses with intact amniotic membranes. Sonographic measurements included
      biparietal diameter, head circumference, abdominal circumference, femur length,
      humerus length, transcerebellar diameter, and sonographically estimated fetal
      weight. Values of the TDFM were each calculated as the mean of 3 separate
      measurements. The 5th, 50th, and 95th percentiles were estimated at each week of
      gestational age (GA) by least squares regression for the mean and SD of the TDFM
      as functions of GA. R(2) and associated P values for the relationships between
      the TDFM and other biometric measurements were calculated. RESULTS: The study
      included 602 consecutive patients meeting the inclusion criteria. The mean
      maternal age +/- SD was 27.5 +/- 6.4 years; median gravidity, 3 (range, 1-12);
      and median parity, 1 (range, 0-7). The mean TDFM was 13.5 +/- 3.7 mm. The
      reference curve formulas for the mean and SD of the TDFM (mm) were TDFM = -12.58
      + GA/0.5616 - GA(2)/24.9 + GA(3)/2430.7, and SD(TDFM) = 1.05 - GA/19.4 +
      GA(2)/588.8. The TDFM correlated significantly and strongly with biparietal
      diameter, head circumference, abdominal circumference, humerus length, femur
      length, transcerebellar diameter, and estimated fetal weight (all R(2) >or= 0.90;
      all P < .0001). CONCLUSIONS: We present reference range nomograms of the TDFM
      between 14 and 40 weeks' gestation.

PMID- 18716140
TI  - Is transabdominal sonography of the cervix after voiding a reliable method of
      cervical length assessment?
AB  - OBJECTIVE: The purpose of this study was to assess the correlation and agreement
      between transvagi-nal and transabdominal cervical length measurement after
      bladder emptying as well as the feasibility of transabdominal sonography in
      cervical length screening. METHODS: This was a prospective cohort study involving
      287 participants (14-34 weeks' gestation) from January to December 2003. After
      voiding, transabdominal and transvaginal cervical length measurements were
      obtained. The optimal trans-abdominal technique was established during an
      unblinded series of transabdominal and transvaginal cervical length measurements
      (n = 96). The same measurements were obtained in 191 participants under a blinded
      2-sonographer protocol. The transabdominal cervical length cutoff to ensure 100%
      sensitivity in detecting a short cervix (<or=2.5 cm) was determined. RESULTS:
      There was no difference between mean transabdominal and transvaginal cervical
      lengths +/- SD (3.57 +/- 0.74 versus 3.61 +/- 0.74 cm; P = .20). The Pearson
      correlation coefficient was 0.824. The 95% tolerance interval for any paired
      observation (transabdominal minus transvaginal) was -0.92 to 0.84 cm. All
      transvaginal cervical lengths of 2.5 cm or less were associated with paired
      transabdominal cervical lengths of 3 cm or less. CONCLUSIONS: With an optimal
      sonographic technique, postvoid transabdominal cervical measurement shows a close
      correlation and agreement with transvaginal assessment and is useful for cervical
      length screening.

PMID- 18716141
TI  - Sonographic carotid plaque morphologic characteristics and vascular risk factors:
      results from a population study.
AB  - OBJECTIVE: The role of vascular risk factors in atherosclerosis development is
      well established, whereas risk factors involved in determining plaque
      vulnerability are still a matter of debate. We investigated the vascular risk
      factor distribution in patients with carotid plaques. METHODS: We consecutively
      assessed sonographic plaque morphologic characteristics, the degree of stenosis,
      and the common carotid artery intima-media thickness (IMT) in 1655 patients.
      Demographic data, a documented history of symptomatic cerebrovascular disease
      (CVD), and the presence of vascular risk factors were collected. According to
      literature, heterogeneous hypoechoic plaques with an irregular surface or
      ulcerations and those with a severe degree of stenosis (>or=70%) have been
      considered "complex" plaques at "major" risk of stroke; homogeneous hyperechoic
      plaques with smooth surface lesions have been considered "simple" plaques at
      minor risk. RESULTS: Univariate analysis showed that all vascular risk factors
      were associated with the presence of carotid atherosclerotic lesions. Multiple
      logistic regression showed an independent association of hypertension and
      diabetes with complex plaques, which also had a thicker IMT. A history of CVD was
      observed more frequently in complex plaques, which had a higher stenosis
      percentage even after patients with a severe degree of stenosis (>or=70%) and
      indications for carotid surgery were excluded. CONCLUSIONS: Hypertension and
      diabetes are related to a thicker IMT and more severe complex plaques, which may
      reflect the instability of atherosclerotic process. Because two-thirds of the
      patients with complex plaques were asymptomatic for CVD, this raises the
      importance of surveillance sonography to monitor plaque evolution for prevention
      of symptomatic CVD.

PMID- 18716142
TI  - Comparison of B-mode ultrasound, 3-dimensional ultrasound, and magnetic resonance
      imaging measurements of carotid atherosclerosis.
AB  - OBJECTIVE: We compared the intraobserver and interscan variability of carotid
      atherosclerosis measured using B-mode ultrasound for quantifying intima media
      thickness (IMT), 3-dimensional ultrasound (3DUS) for quantifying vessel wall
      volume (VWV) and total plaque volume (TPV), and magnetic resonance imaging (MRI)
      for measuring VWV. We also evaluated the associations of these measurements and
      sample sizes required to detect specific changes in patients with moderate
      atherosclerosis. METHODS: Ten patients were evaluated with B-mode ultrasound,
      MRI, and 3DUS twice within 14 +/- 2 days. Measurements of IMT, MRI VWV, 3DUS VWV,
      and 3DUS TPV were performed by single observers using manual (VWV and TPV) and
      semiautomated (IMT) segmentation. RESULTS: Intraobserver coefficients of
      variation were 3.4% (IMT), 4.7% (3DUS VWV), 6.5% (MRI VWV), and 23.9% (3DUS TPV).
      Interscan coefficients of variation were 8.1% (MRI VWV), 8.9% (IMT), 13.5% (3DUS
      VWV), and 46.6% (3DUS TPV). Scan-rescan linear regressions were significant for
      3DUS TPV (R(2) = 0.57), 3DUS VWV (R(2) = 0.59), and IMT (R(2) = 0.75) and
      significantly different (P < .05) for MRI VWV (R(2) = 0.87). CONCLUSIONS: B-mode
      ultrasound-derived IMT provided the highest intraobserver and interscan
      reproducibility. Three-dimensional measurements of VWV derived from 3DUS and MRI
      provided both high sensitivity and high intraobserver and interscan reliability.

PMID- 18716143
TI  - Carotid stenosis assessed with a 4-dimensional semiautomated Doppler system.
AB  - OBJECTIVE: The purpose of this study was to compare peak systolic velocities
      (PSVs) and the degree of stenosis obtained with a real-time 3-dimensional (ie, 4
      dimensional) Doppler ultrasound scanner (Encore PV; VueSonix Sensors Inc, Wayne,
      PA) to conventional Doppler ultrasound imaging of the carotid arteries (common
      [CCA], internal [ICA], and external [ECA]). A secondary goal was to assess Encore
      volume flow measurements. METHODS: Seventy patients referred for clinical carotid
      ultrasound participated in this pilot study. Peak systolic velocities of the CCA,
      ECA, and ICA were obtained bilaterally. The degree of stenosis in the ICA was
      calculated based on the ICA PSV and ICA/CCA PSV ratio. The Encore detects all 3
      dimensional blood flow velocity vectors within 10-s longitudinal volumes of the
      ICA, ECA, and CCA. On the Encore, a reader determined the centerline of the
      vessels. The PSV and volume flow were then automatically calculated. The flow
      measurement error was obtained by comparing the CCA flow to the ICA and ECA flow.
      Data were compared using linear regression, intraclass correlation coefficients
      (ICCs), and Bland-Altman analysis. RESULTS: Due to technical difficulties, only
      59 patients (323 vessel segments) were available for analysis. There was good
      agreement between methods for assessing the degree of stenosis based on the ICA
      PSV (ICC = 0.83; P < .0001) and, to a lesser degree, on the ICA/CCA PSV ratio
      (ICC = 0.65; P < .0001). Peak systolic velocity measurements obtained with
      conventional ultrasound and the Encore correlated in all vessels (r >or= 0.32; P
      < .002), and Bland-Altman analysis showed reasonable variations. The Encore mean
      volume flow error +/- SD was -4.1% +/- 66.4% and was not biased (P = .57).
      CONCLUSIONS: A new semiautomated 4-dimensional Doppler device is comparable to
      conventional Doppler ultrasound for assessment of carotid stenosis.

PMID- 18716144
TI  - Characteristic sonographic findings of early restenosis after carotid
      endarterectomy.
AB  - OBJECTIVE: Restenosis of the carotid artery after carotid endarterectomy (CEA) is
      a major complication. The frequency, time of occurrence, and tissue
      characteristics of carotid restenosis were assessed with sonography. METHODS: Two
      hundred sixteen patients who had CEA for carotid stenosis were studied; follow-up
      sonography and magnetic resonance angiography were done 2 weeks, 3 months, and
      then every year after CEA. On sonography, restenosis was defined as an internal
      carotid artery (ICA) with a peak systolic velocity of 170 cm/s or greater or a
      maximum area of stenosis of 90% or greater. RESULTS: During 605 artery-years of
      follow-up, 18 patients (7.5%) were found to have restenosis on sonography: 4 at 3
      months, 11 at 1 year, and 3 at 2 years after CEA. At the time that restenosis was
      detected, in all 18 ICAs the peak systolic velocity exceeded 200 cm/s and had
      more than doubled since the last measurement (mean +/- SD, 103 +/- 27 to 321 +/
      107 cm/s), whereas the area of stenosis exceeded 90% in 6 patients, and magnetic
      resonance angiography revealed stenosis of 60% or greater in 8 patients. On
      sonography, all of the restenotic plaques were isoechoic and concentric. The
      restenosis was asymptomatic in 17 patients. Vascular risk factors or the severity
      of initial carotid stenosis before CEA were not associated with development of
      restenosis. Eleven patients had successful endovascular therapy, and the others
      received medical treatment. CONCLUSIONS: A marked increase in the flow velocity
      through an operated ICA is a good indication of restenosis. The isoechogenicity
      and concentricity of the restenotic plaques suggest that the restenosis is
      primarily the result of intimal hyperplasia.

PMID- 18716145
TI  - Real-time measurement system for evaluation of the carotid intima-media thickness
      with a robust edge operator.
AB  - OBJECTIVE: The purpose of this report is to describe an automatic real-time
      system for evaluation of the carotid intima-media thickness (CIMT) characterized
      by 3 main features: minimal interobserver and intraobserver variability, real
      time capabilities, and great robustness against noise. METHODS: One hundred fifty
      carotid B-mode ultrasound images were used to validate the system. Two skilled
      operators were involved in the analysis. Agreement with the gold standard,
      defined as the mean of 2 manual measurements of a skilled operator, and the
      interobserver and intraobserver variability were quantitatively evaluated by
      regression analysis and Bland-Altman statistics. RESULTS: The automatic measure
      of the CIMT showed a mean bias +/- SD of 0.001 +/- 0.035 mm toward the manual
      measurement. The intraobserver variability, evaluated with Bland-Altman plots,
      showed a bias that was not significantly different from 0, whereas the SD of the
      differences was greater in the manual analysis (0.038 mm) than in the automatic
      analysis (0.006 mm). For interobserver variability, the automatic measurement had
      a bias that was not significantly different from 0, with a satisfactory SD of the
      differences (0.01 mm), whereas in the manual measurement, a little bias was
      present (0.012 mm), and the SD of the differences was noticeably greater (0.044
      mm). CONCLUSIONS: The CIMT has been accepted as a noninvasive marker of early
      vascular alteration. At present, the manual approach is largely used to estimate
      CIMT values. However, that method is highly operator dependent and time
      consuming. For these reasons, we developed a new system for the CIMT measurement
      that conjugates precision with real-time analysis, thus providing considerable
      advantages in clinical practice.

PMID- 18716146
TI  - Fine-tuning the diagnosis of fetal scalp cysts: the value of high-frequency
      sonography.
AB  - OBJECTIVE: The purpose of this series is to emphasize the importance of an
      exhaustive and appropriately conducted sonographic examination in the correct
      diagnosis of fetal cystic scalp lesions and the place of magnetic resonance
      imaging (MRI) in the diagnostic sequence. METHODS: Transabdominal and
      transvaginal 2- and 3-dimensional sonography with color and power Doppler imaging
      as well as 3-dimensional rendering techniques such as inversion and Doppler
      angiography were used. In 1 case, an MRI study was performed. RESULTS: In 1 case,
      the MRI missed and the different sonographic techniques correctly made the
      diagnosis of a meningocele. In the second case, sonography was sufficient to
      establish the diagnosis of an epidermal cyst. CONCLUSIONS: These 2 cases show the
      value of going the distance with the newly available high-frequency sonography.
      Ultimately, the correct diagnoses were made with the tools offered by sonography
      without the need for any other imaging modality.

PMID- 18716147
TI  - Prenatal diagnosis of a fetal epidural hematoma using 2- and 3-dimensional
      sonography and magnetic resonance imaging.

PMID- 18716148
TI  - Postpartum management of placenta previa accreta left in situ: role of 3
      dimensional angiography.

PMID- 18716149
TI  - Fetus in fetu: 11 fetoid forms in a single fetus: review of the literature and
      imaging.

PMID- 18716150
TI  - Four-vessel umbilical cord: not always a dire prognosis.

PMID- 18716151
TI  - Replacement lipomatosis of the kidney: sonographic features.

PMID- 18716152
TI  - Benign intracystic papilloma of the male breast.

PMID- 18716153
TI  - Primary neuroendocrine carcinoma of the breast involving the nipple-areolar
      complex.

PMID- 18716154
TI  - Intraductal foreign body in the breast found on sonography.

PMID- 18716155
TI  - Nutrients, endpoints, and the problem of proof.

PMID- 18716156
TI  - Green tea attenuates angiotensin II-induced cardiac hypertrophy in rats by
      modulating reactive oxygen species production and the Src/epidermal growth factor
      receptor/Akt signaling pathway.
AB  - We previously documented a clear-cut antihypertensive effect of green teat
      extract (GTE), which was associated with correction of endothelial dysfunction
      and prevention of left ventricular hypertrophy in an angiotensin II (Ang II)
      dependent model of hypertension, but the molecular mechanisms remain to be
      defined. As several effects of Ang II involve production of reactive oxygen
      species (ROS) and activation of 2nd messengers, such as mitogen-activated protein
      kinase (MAPK) and Akt, we investigated the effect of GTE on these signal
      transduction pathways in Ang II-treated rats. Rats were treated for 2 wk with Ang
      II infusion (700 mug.kg(-1).d(-1); n = 6, via osmotic minipumps), Ang II plus GTE
      (6 g/L) dissolved in the drinking water; n = 6), or vehicle (n = 6) to serve as
      controls. Blood pressure was monitored by telemetry throughout the study. The
      activation and expression of NAD(P)H oxidase subunits, protein kinase C isoforms,
      Src, epidermal growth factor receptor (EGFR), Akt, and MAPK were determined in
      the heart in vitro through immunoprecipitation and western blot analysis with
      specific antibodies. NAD(P)H oxidase enzymatic activity was measured by
      cytochrome c reduction assay. GTE blunted Ang II-induced blood pressure increase
      and cardiac hypertrophy. In Ang II-treated rats, GTE decreased the expression of
      the NAD(P)H oxidase subunit gp91(phox) and the translocation of Rac-1, as well as
      NAD(P)H oxidase enzymatic activity. Furthermore, it specifically reduced Ang II
      induced Src, EGFR, and Akt phosphorylation. These results show that GTE blunts
      Ang II-induced cardiac hypertrophy specifically by regulating ROS production and
      the Src/EGFR/Akt signaling pathway activated by Ang II.

PMID- 18716157
TI  - Resveratrol, at concentrations attainable with moderate wine consumption,
      stimulates human platelet nitric oxide production.
AB  - The mechanisms through which moderate wine consumption reduces ischemic
      cardiovascular events are not yet fully unraveled. Grape extracts or a mixture of
      the polyphenols contained in wine were previously shown to increase nitric oxide
      (NO); however, little information is available on the effect of resveratrol, one
      of the main polyphenols of wine, on platelet NO production. We assessed the
      effects of resveratrol, at the concentrations attainable after moderate wine
      intake, on platelet NO production and the mechanism of this activity. Twenty
      healthy volunteers were studied before and after 15 d of controlled white or red
      wine intake (300 mL/d). After wine intake, plasma resveratrol and the release of
      NO by stimulated platelets increased significantly. Resveratrol, at the
      concentrations detected in plasma after wine intake, was incubated in vitro with
      washed platelets and several variables related to NO production and to signal
      transduction were measured. Resveratrol in vitro enhanced significantly the
      production of NO by stimulated platelets, the activity of platelet NO synthase
      (NOS), phosphorylation of protein kinase B, an activator of the endothelial NOS
      (eNOS), and phosphorylation of vasodilator-activated protein (VASP), an
      expression of the biologic activity of NO in platelets. Simultaneously, we
      observed decreased phosphorylation of P38 mitogen-activated protein kinase
      (p38MAPK), a proinflammatory pathway in human platelets, a reduction of the
      activity of NADPH oxidase, a major source of reactive oxygen species (ROS) and of
      the generation of O(2)(-) radicals, as detected by cytochrome C reduction. In
      conclusion, resveratrol, at concentrations attainable after moderate wine intake,
      activates platelet eNOS and in this way blunts the proinflammatory pathway linked
      to p38MAPK, thus inhibiting ROS production and ultimately platelet function. This
      activity may contribute to the beneficial effects of moderate wine intake on
      ischemic cardiovascular disease.

PMID- 18716158
TI  - Adiponectin gene variants are associated with insulin sensitivity in response to
      dietary fat consumption in Caucasian men.
AB  - Adiponectin (adipoQ) gene variants have been associated with type 2 diabetes
      mellitus and insulin resistance. Our aim was to examine whether the presence of
      several polymorphisms at the adipoQ gene locus (-11391 G > A, -11377 C > G, 45 T
      > G, and 276 G > T) influences the insulin sensitivity to dietary fat. Healthy
      volunteers (30 men and 29 women) consumed 3 diets for 4 wk each: an initial
      period during which all subjects consumed a SFA-rich diet (38% total fat, 20%
      SFA), followed by a carbohydrate-rich diet (CHO) (30% total fat, 55%
      carbohydrate) or a monounsaturated fatty acid (MUFA)-rich diet (38% total fat,
      22% MUFA) following a randomized, crossover design. After participants consumed
      each diet, we tested peripheral insulin sensitivity with the insulin suppression
      test and measured plasma adiponectin concentrations. C/C homozygous men for the 
      11377 C > G single nucleotide polymorphism (SNP) had a significantly greater
      decrease in the steady-state plasma glucose concentrations when changing from the
      SFA-rich (8.95 +/- 0.6 mmol/L) to the MUFA-rich (6.04 +/- 0.31 mmol/L) and CHO
      rich (6.35 +/- 0.38 mmol/L) diets than did those carrying the minor G allele
      (SFA, 6.65 +/- 0.4 mmol/L; MUFA, 6.45 +/- 0.4 mmol/L; CHO, 5.83 +/- 0.3 mmol/L)
      (P sex x gene x diet interaction = 0.016). These differences did not occur in
      female participants. Furthermore, C/C men had lower plasma adiponectin
      concentrations than did C/C women (P sex x gene interaction = 0.015),
      independently of the dietary fat consumed. None of the variables examined were
      significantly associated with -11426 A > G, 45T > G, or 276 G > T SNP. In
      conclusion, C/C homozygous men for the -11377 C > G SNP at adipoQ gene were
      significantly less insulin resistant after consumption of the MUFA- and CHO-rich
      diets compared with the SFA-rich diet. This information should help in the
      identification of vulnerable populations or persons who will benefit from more
      personalized and mechanism-based dietary recommendations.

PMID- 18716159
TI  - Daily quercetin supplementation dose-dependently increases plasma quercetin
      concentrations in healthy humans.
AB  - Our aim was to investigate the effects of an oral supplementation of quercetin at
      3 different doses on plasma concentrations of quercetin, parameters of
      oxidant/antioxidant status, inflammation, and metabolism. To this end, 35 healthy
      volunteers were randomly assigned to take 50, 100, or 150 mg/d (group Q50-Q150)
      quercetin for 2 wk. Fasting blood samples were collected at the beginning and end
      of the supplementation period. Compared with baseline, quercetin supplementation
      significantly increased plasma concentrations of quercetin by 178% (Q50), 359%
      (Q100), and 570% (Q150; P < 0.01 for all). High interindividual variation was
      found for plasma quercetin concentrations (36-57%). Quercetin did not affect
      concentrations of serum uric acid or plasma alpha- and gamma-tocopherols,
      oxidized LDL, and tumor necrosis factor-alpha, or plasma antioxidative capacity
      as assessed by the ferric-reducing antioxidant potential and oxygen radical
      absorbance capacity assays. In addition, serum lipids and lipoproteins, body
      composition, and resting energy expenditure did not significantly change during
      quercetin supplementation. Pharmacokinetics of quercetin were investigated in a
      subgroup of 15 volunteers. The areas under the plasma concentration-time curves
      ranged from 76.1 mumol.min.L(-1) to 305.8 mumol.min.L(-1) (50- and 150-mg
      dosages, respectively). Median maximum plasma concentrations of quercetin (431
      nmol/L) were observed 360 min after intake of 150 mg quercetin. In conclusion,
      daily supplementation of healthy humans with graded concentrations of quercetin
      for 2 wk dose-dependently increased plasma quercetin concentrations but did not
      affect antioxidant status, oxidized LDL, inflammation, or metabolism.

PMID- 18716160
TI  - Early undernutrition leads to long-lasting reductions in body weight and
      adiposity whereas increased intake increases cardiac fibrosis in male rats.
AB  - Previous studies suggest that both overfeeding and undernutrition during
      development increase the risk of obesity and hypertension in adulthood. In this
      study, we examined both short- (24 d) and long- (16 wk) term effects of early
      postnatal over- and underfeeding in rats on body weight, body composition, plasma
      hormones, adiposity markers, and hypothalamic neuropeptide Y content.
      Cardiovascular changes were also examined by measuring blood pressure and cardiac
      fibrosis. Rats raised in litters of 3, 12, or 18 pups per mother were used to
      model early onset overfeeding, control, and underfeeding, respectively. At 24 d
      of age, pups raised in small litters (SL) were 10% heavier than pups from normal
      litters, accompanied by increased organ mass and fat mass, elevated plasma
      leptin, corticosterone, and uncoupling protein-1 mRNA in brown adipose tissue. On
      the other hand, pups raised in large litters were 17% lighter with no significant
      changes in plasma leptin. Overfeeding during the first 3 wk of life led to
      increased plasma leptin concentration in adulthood, whereas underfed rats
      remained significantly lighter throughout the study, with no evidence of catch-up
      growth. Rats raised in SL were more susceptible to developing cardiac fibrosis
      with a 22% increase in collagen deposition compared with control rats at 16 wk of
      age (P < 0.05). This was independent of any changes in blood pressure. This study
      demonstrates that nutritional changes early in postnatal development can have
      long-lasting effects on body weight, adiposity, and some mediators involved in
      energy homeostasis and can also lead to structural changes in the heart in
      adulthood. This highlights the importance of identifying potential early life
      risk factors involved in the modulation of childhood nutrition.

PMID- 18716161
TI  - Excess dietary L-cysteine causes lethal metabolic acidosis in chicks.
AB  - A 72-h time-course study was conducted to elucidate the physiological mechanism
      underlying cysteine (Cys) toxicity in chicks beginning at 8-d posthatch.
      Biochemical markers quantified in plasma and liver samples collected from chicks
      receiving 30 g/kg excess dietary Cys were compared with baseline measurements
      from chicks receiving an unsupplemented corn-soybean meal diet over a 72-h
      feeding period. Concomitant with chick mortality were indices of acute metabolic
      acidosis, including a rapid increase (P < 0.001) in anion gap that resulted from
      a reduction (P < 0.001) in plasma HCO(3)(-) of approximately 40% and a 2.8-fold
      increase (P < 0.001) in plasma sulfate in chicks receiving excess Cys.
      Additionally, provision of 30 g/kg excess Cys resulted in a 1.5-fold increase (P
      < 0.05) in hepatic oxidized glutathione compared with the 0-h control time-point.
      Excess dietary Cys did not affect plasma free Met, but plasma free Cys increased
      (P < 0.05) from 89 to 107 mumol/L at 12 h and remained elevated through 36 h.
      Strikingly, ingestion of 30 g/kg excess Cys caused more than a doubling (P <
      0.001) of plasma free cystine, the oxidized form of Cys, beginning 12 h after
      initiating the study, and it remained elevated throughout the 72-h feeding
      period. Taken together, these data suggest that ingestion of 30 g/kg excess l-Cys
      causes both acute metabolic acidosis and oxidative stress in young chicks when
      fed a nutritionally adequate, corn-soybean meal diet.

PMID- 18716162
TI  - A specific blend of intact protein rich in aspartate has strong postprandial
      glucose attenuating properties in rats.
AB  - Three studies were carried out to help define an optimal protein blend for use in
      a nutritional product for diabetic patients. To this end, we tested the effects
      of coinfusions of combinations of different types of carbohydrates and proteins
      on the postprandial glycemic plasma response in healthy rats. Expt. 1 compared
      the effects of administering different forms of soy protein (intact protein, its
      hydrolysate, or an equivalent amount of the same amino acids), all in combination
      with a fixed amount of glucose (Glu), on postprandial Glu and insulin plasma
      concentrations. Intact soy protein (SI) had stronger insulinogenic properties
      compared with its hydrolysate but was equally potent in reducing the postprandial
      Glu response. In Expt. 2, we compared the effect of replacing 50% of the SI with
      the whey-derived protein alpha-lactalbumin when coingested with maltodextrin as
      the carbohydrate source. Only the specific aspartate-rich blend of SI and alpha
      lactalbumin significantly improved the postprandial Glu response. In Expt. 3, we
      studied the effect of using the blend of SI and alpha-lactalbumin combined with a
      slowly digestible carbohydrate. The protein blend was still capable of
      significantly decreasing the postprandial Glu response even when a slow-release
      carbohydrate source was included. Combining this aspartate-rich protein blend
      with a slow-release carbohydrate might therefore lead to a low-glycemic
      nutritional product beneficial for dietary management in diabetic patients.

PMID- 18716163
TI  - Elevated tissue betaine contents in developing rats are due to dietary betaine,
      not to synthesis.
AB  - The time course of betaine accumulation and activities of enzymes involved in
      betaine metabolism were studied in developing rats. In study 1, pups weaned on a
      nonpurified diet had a transient increase in liver and kidney betaine content
      followed by a decline after approximately 42-56 d. In study 2, dams and,
      following weaning, pups were fed an AIN-93G (betaine-free) or an AIN-93G betaine
      supplemented diet (0.3%) to determine the source of the transient increase in
      betaine levels previously observed. In study 2, only rats fed betaine had an
      increase in plasma betaine concentration. Similarly, liver and kidney betaine
      contents increased postweaning; however, betaine levels returned to that found in
      rats fed a betaine-free diet by 49 d of age. The dietary content of betaine fed
      to dams did not affect pup betaine. The activities of choline dehydrogenase, an
      enzyme of betaine synthesis, and betaine:homocysteine methyltransferase (BHMT),
      which is the only known betaine-consuming enzyme in mammals, were also measured
      in study 2. Liver BHMT activity decreased after weaning, whereas liver and kidney
      choline dehydrogenase activity increased with age, possibly reaching a plateau by
      42 d of age. We conclude that the transient increase in betaine reflects high
      dietary betaine and not a change in endogenous betaine synthesis.

PMID- 18716164
TI  - Bioactive dietary polyphenolic compounds reduce nonheme iron transport across
      human intestinal cell monolayers.
AB  - There is persuasive epidemiological evidence that regular intake of dietary
      bioactive polyphenolic compounds promotes human health. Because dietary
      polyphenolic compounds have a wide range of effects in vivo and vitro, including
      chelation of metals such as iron, it is prudent to test whether the regular
      consumption of bioactive polyphenolic components impair the utilization of
      dietary iron. We examined the influence of the dietary polyphenols (-) 
      epigallocatechin-3-gallate (EGCG) and grape seed extract (GSE) on transepithelial
      iron transport in Caco-2 intestinal cells. The range of EGCG and GSE
      concentrations used in this study was within physiological levels and did not
      affect the integrity of differentiated Caco-2 cell monolayers. Both EGCG and GSE
      decreased (P < 0.001) transepithelial iron transport. However, apical iron uptake
      was increased (P < 0.001) by the addition of EGCG and GSE. The increased uptake
      of iron might be due in part to the reducing activity of EGCG and GSE. Both EGCG
      and GSE reduced approximately 15% of the applied Fe(3+) to Fe(2+) in the uptake
      buffer. Despite the increased cellular levels of (55)Fe, the transfer of iron
      across the basolateral membrane of the enterocyte was extremely low, indicating
      that basolateral exit via ferroportin-1 was impaired, possibly through formation
      of a nontransportable polyphenol-iron complex. Our data show that polyphenols
      inhibit nonheme iron absorption by reducing basolateral iron exit rather than by
      decreasing apical iron import in intestinal cells.

PMID- 18716165
TI  - Arginine stimulates cdx2-transformed intestinal epithelial cell migration via a
      mechanism requiring both nitric oxide and phosphorylation of p70 S6 kinase.
AB  - In intestinal cells, arginine (Arg) is 1 of the 2 most potent amino acid
      activators of p70(s6k), a key regulator of 5'- terminal oligopyrimidine mRNA
      translation, a necessary condition for increased cell migration. To investigate
      the mechanism of response to Arg, we used the rat crypt cell line cdx2
      transformed IEC-6 cells (cdx2-IEC) and measured cell migration,
      immunocytochemical analysis of p70(s6k) activation in response to Arg, and
      production of nitric oxide (NO). When treated with Arg, cdx2-IEC increased in
      phosphorylation on Thr-389 of p70(s6k) (pp70(s6k)) compared with control (P <
      0.01). Phospho-Thr-421/Ser-424-p70(s6k) was located in the nucleus shortly after
      Arg treatment. Arg enhanced pp70(s6k), cell migration (55% wound coverage), and
      NO production. In comparison, the branched-chain amino acid leucine (Leu)
      activated pp70(s6k), was a weaker stimulator of migration (23% coverage), and did
      not increase NO. A total of 25 micromol/L DETA-NONOate (DETA/NO) did not
      significantly enhance phosphorylation of p70(s6k) but enhanced the rate of cell
      migration by approximately 25%. Wound coverage with Leu plus DETA/NO (25
      micromol/L) was greater than coverage with DETA/NO alone (P < 0.01). These and
      our previous studies lead to a model in which Arg must stimulate both pp70(s6k)
      (in the nucleus) and NO release to enhance intestinal epithelial cell migration,
      which may be relevant to diseases that involve intestinal villous injury.

PMID- 18716166
TI  - Dietary calcium and cholecalciferol modulate cyclin D1 expression, apoptosis, and
      tumorigenesis in intestine of adenomatous polyposis coli1638N/+ mice.
AB  - Both epidemiological and experimental findings have indicated that components of
      Western diets influence colonic tumorigenesis. Among dietary constituents,
      calcium and cholecalciferol have emerged as promising chemopreventive agents. We
      have demonstrated that a Western-style diet (WD) with low levels of calcium and
      cholecalciferol and high levels of (n-6) PUFA, increased the incidence of
      neoplasia in mouse intestine compared with a standard AIN-76A diet; models
      included wild-type mice and mice with targeted mutations. In the present study,
      adenomatous polyposis coli (Apc)(1638N/+) mice carrying a heterozygous Apc
      mutation were fed either an AIN-76A diet, a WD, or a WD supplemented with calcium
      and cholecalciferol (WD/Ca/VitD3). Diets were fed for 24 wk and effects on
      cellular and molecular events were assessed by performing immunohistochemistry in
      colonic epithelium along the crypt-to-surface continuum. Feeding WD to
      Apc(1638N/+) mice not only enhanced cyclin D1 expression in colonic epithelium
      compared with AIN-76A treatment as previously reported but also significantly
      increased the expression of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2)
      concomitantly with a decrease in the proapoptotic Bcl2-associated X protein and
      the number of apoptotic epithelial cells. WD treatment enhanced mutant Apc-driven
      small intestinal carcinogenesis and also resulted in the formation of a small
      number of colonic adenomas (0.16 +/- 0.09; P < 0.05). By contrast, the
      WD/Ca/VitD3 diet reversed WD-induced growth, promoting changes in colonic
      epithelium. Importantly, Apc(1638N/+) mice fed the WD/Ca/VitD3 diet did not
      develop colonic tumors, further indicating that dietary calcium and
      cholecalciferol have a key role in the chemoprevention of colorectal neoplasia in
      this mouse model of human colon cancer.

PMID- 18716167
TI  - Zinc deficiency induces membrane barrier damage and increases neutrophil
      transmigration in Caco-2 cells.
AB  - Zinc may contribute to the host defense by maintaining the membrane barrier. In
      this study, we questioned whether zinc deficiency affects the membrane function
      and junctional structure of intestinal epithelial cells, causing increased
      neutrophil migration. We used the Caco-2 cell line grown in control (C), zinc
      deficient, or zinc-replete medium until differentiation. Zinc deprivation induced
      a decrease of transepithelial electrical resistance and alterations to tight and
      adherens junctions, with delocalization of zonula occludens (ZO-1), occludin,
      beta-catenin, and E-cadherin. Disorganization of F-actin and beta-tubulin was
      also found in zinc deficiency. These changes were associated with a loss of the
      amounts of ZO-1, occluding, and beta-tubulin. In addition, zinc deficiency caused
      a dephosphorylation of occludin and hyperphosphorylation of beta-catenin and ZO
      1. Disruption of membrane barrier integrity led to increased migration of
      neutrophils. In addition, zinc deficiency induced an increase in the secretion of
      interleukin-8, epithelial neutrophil activating peptide-78, and growth-regulated
      oncogene-alpha, alterations that were not found when culture medium was replete
      with zinc. These results provide new information on the critical role played by
      dietary zinc in the maintenance of membrane barrier integrity and in controlling
      inflammatory cell infiltration.

PMID- 18716168
TI  - Blood pressure is reduced and insulin sensitivity increased in glucose
      intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark
      chocolate.
AB  - Flavanols from chocolate appear to increase nitric oxide bioavailability, protect
      vascular endothelium, and decrease cardiovascular disease (CVD) risk factors. We
      sought to test the effect of flavanol-rich dark chocolate (FRDC) on endothelial
      function, insulin sensitivity, beta-cell function, and blood pressure (BP) in
      hypertensive patients with impaired glucose tolerance (IGT). After a run-in
      phase, 19 hypertensives with IGT (11 males, 8 females; 44.8 +/- 8.0 y) were
      randomized to receive isocalorically either FRDC or flavanol-free white chocolate
      (FFWC) at 100 g/d for 15 d. After a wash-out period, patients were switched to
      the other treatment. Clinical and 24-h ambulatory BP was determined by
      sphygmometry and oscillometry, respectively, flow-mediated dilation (FMD), oral
      glucose tolerance test, serum cholesterol and C-reactive protein, and plasma
      homocysteine were evaluated after each treatment phase. FRDC but not FFWC
      ingestion decreased insulin resistance (homeostasis model assessment of insulin
      resistance; P < 0.0001) and increased insulin sensitivity (quantitative insulin
      sensitivity check index, insulin sensitivity index (ISI), ISI(0); P < 0.05) and
      beta-cell function (corrected insulin response CIR(120); P = 0.035). Systolic (S)
      and diastolic (D) BP decreased (P < 0.0001) after FRDC (SBP, -3.82 +/- 2.40 mm
      Hg; DBP, -3.92 +/- 1.98 mm Hg; 24-h SBP, -4.52 +/- 3.94 mm Hg; 24-h DBP, -4.17 +/
      3.29 mm Hg) but not after FFWC. Further, FRDC increased FMD (P < 0.0001) and
      decreased total cholesterol (-6.5%; P < 0.0001), and LDL cholesterol (-7.5%; P <
      0.0001). Changes in insulin sensitivity (Delta ISI - Delta FMD: r = 0.510, P =
      0.001; Delta QUICKI - Delta FMD: r = 0.502, P = 0.001) and beta-cell function
      (Delta CIR(120) - Delta FMD: r = 0.400, P = 0.012) were directly correlated with
      increases in FMD and inversely correlated with decreases in BP (Delta ISI - Delta
      24-h SBP: r = -0.368, P = 0.022; Delta ISI - Delta 24-h DBP r = -0.384, P =
      0.017). Thus, FRDC ameliorated insulin sensitivity and beta-cell function,
      decreased BP, and increased FMD in IGT hypertensive patients. These findings
      suggest flavanol-rich, low-energy cocoa food products may have a positive impact
      on CVD risk factors.

PMID- 18716169
TI  - The major green tea polyphenol, (-)-epigallocatechin-3-gallate, inhibits obesity,
      metabolic syndrome, and fatty liver disease in high-fat-fed mice.
AB  - In this study, we investigated the effects of the major green tea polyphenol, (-)
      epigallocatechin-3-gallate (EGCG), on high-fat-induced obesity, symptoms of the
      metabolic syndrome, and fatty liver in mice. In mice fed a high-fat diet (60%
      energy as fat), supplementation with dietary EGCG treatment (3.2 g/kg diet) for
      16 wk reduced body weight (BW) gain, percent body fat, and visceral fat weight (P
      < 0.05) compared with mice without EGCG treatment. The BW decrease was associated
      with increased fecal lipids in the high-fat-fed groups (r(2) = 0.521; P < 0.05).
      EGCG treatment attenuated insulin resistance, plasma cholesterol, and monocyte
      chemoattractant protein concentrations in high-fat-fed mice (P < 0.05). EGCG
      treatment also decreased liver weight, liver triglycerides, and plasma alanine
      aminotransferase concentrations in high-fat-fed mice (P < 0.05). Histological
      analyses of liver samples revealed decreased lipid accumulation in hepatocytes in
      mice treated with EGCG compared with high-fat diet-fed mice without EGCG
      treatment. In another experiment, 3-mo-old high-fat-induced obese mice receiving
      short-term EGCG treatment (3.2 g/kg diet, 4 wk) had decreased mesenteric fat
      weight and blood glucose compared with high-fat-fed control mice (P < 0.05). Our
      results indicate that long-term EGCG treatment attenuated the development of
      obesity, symptoms associated with the metabolic syndrome, and fatty liver. Short
      term EGCG treatment appeared to reverse preexisting high-fat-induced metabolic
      pathologies in obese mice. These effects may be mediated by decreased lipid
      absorption, decreased inflammation, and other mechanisms.

PMID- 18716170
TI  - Lactobacillus reuteri 100-23 transiently activates intestinal epithelial cells of
      mice that have a complex microbiota during early stages of colonization.
AB  - Monoassociations of germ-free animals with colitogenic and probiotic bacterial
      strains trigger intestinal epithelial cell (IEC) activation and host-derived
      feedback mechanisms. To characterize the impact of a single nonpathogenic
      bacterial strain on the intestinal epithelium in the presence of an established
      microbiota, we inoculated reconstituted Lacotobacillus-free (RLF) mice at 8 wk of
      age with Lactobacillus reuteri 100-23. Primary IEC from the small intestine of L.
      reuteri-inoculated and control RLF mice were isolated 2, 6, and 21 d after
      inoculation followed by gene expression analysis (real-time PCR; Affymetrix
      microarrays) as well as 2-dimensional-gel electrophoreses (2D SDS-PAGE) and
      peptide mass fingerprinting via matrix-assisted laser desorption/ionization time
      of flight MS. At d 6, gene expression of proinflammatory cytokines and chemokines
      including interleukin (IL)-1alpha, IL-6, interferon-gamma-inducible protein 10,
      and macrophage inflammatory protein 2 was transiently induced, whereas gene
      expression levels of regulatory proteins A20 and Toll-interacting protein
      decreased. In addition, 8 target proteins with changes in the steady-state
      protein expression levels were identified at d 2 and 6 of L. reuteri
      colonization. Consistent with the absence of histopathology, L. reuteri-induced
      activation of primary IEC returned to control levels by d 21 after inoculation of
      RLF mice. The capability of L. reuteri 100-23 to directly trigger epithelial cell
      activation was confirmed in small IEC cultures using the murine cell line Mode-K.
      These results clearly indicate that the intestinal epithelium is reactive toward
      environmental changes induced by the commensal bacterial strain L. reuteri even
      in the presence of an already-established microbiota. The induction of transient
      IEC activation may help to maintain mucosal homeostasis.

PMID- 18716171
TI  - Biofortified carrot intake enhances liver antioxidant capacity and vitamin a
      status in mongolian gerbils.
AB  - Biofortification efforts have increased concentrations of bioactive compounds in
      carrots. We measured the antioxidant potential and vitamin A bioefficacy of 4
      biofortified carrot varieties [purple/orange, purple/orange/red, orange/red, and
      orange] in Mongolian gerbils (n = 73). Following a 4-wk vitamin A depletion
      period and baseline kill (n = 7), freeze-dried carrot powders were mixed into
      purified feeds and fed to 6 groups (n = 11/group) for 4 wk. White carrot-fed
      control and vitamin A-supplemented groups were used to calculate carrot
      provitamin A bioefficacy. Antioxidant capacities of carrot powders, sera, and
      livers were determined using the 2, 2'-azinobis-(3-ethylbenzothiazoline-6
      sulfonic acid) radical cation decolorization assay and carotenoid and retinol
      concentrations were determined by HPLC. Antioxidant capacity of liver extracts
      from the 4 colored carrot-fed groups [10.1 +/- 1.2 mumol Trolox equivalent
      antioxidant capacity (TEAC)/g] was significantly higher than the white carrot-fed
      control group (9.3 +/- 0.9 mumol TEAC/g) and vitamin A-supplemented group (8.8 +/
      1.4 mumol TEAC/g) (P < 0.05). Liver retinol stores in the colored carrot-fed
      groups (0.62 +/- 0.13 to 0.67 +/- 0.08 mumol retinol/liver) did not differ and
      were higher than the white carrot-fed control group (0.32 +/- 0.08 mumol
      retinol/g) (P < 0.0001). Serum antioxidant capacity and retinol did not differ
      among treatment groups. Liver antioxidant capacity and vitamin A stores were
      higher in gerbils fed colored carrots than in those fed white carrots.
      Antioxidant activity is one of several proposed mechanisms by which plant foods,
      like biofortified carrots, may provide additional health benefits beyond
      maintenance of vitamin A status.

PMID- 18716172
TI  - Adherence to dietary recommendations for saturated fat, fiber, and sodium is low
      in American Indians and other U.S. adults with diabetes.
AB  - The objective of this article was to evaluate how well American Indians with
      diabetes met dietary recommendations and to compare adherence to dietary
      recommendations with those of U.S. adults with diabetes in the NHANES. Dietary
      intake in both studies was assessed using a 24-h recall questionnaire. Dietary
      intakes were evaluated against American Diabetes Association (ADA) dietary
      recommendations. The analysis sample consisted of 1008 participants from the
      Strong Heart Study (SHS) examined from 1997 to 1999 and 373 participants from
      NHANES examined from 1999 to 2000, all with diabetes. In both samples, intake of
      protein, PUFA, monounsaturated fatty acids, and carbohydrates met the 1997 ADA
      dietary recommendations. However, intakes of SFA as well as sodium were higher
      and dietary fiber intake was lower than recommended. In the SHS and NHANES, only
      4.6 and 8.5% of persons with diabetes met recommendations for both SFA and fiber
      (P = 0.02), respectively. However, only 8.3% of the NHANES sample met the 2006
      recommendations for SFA and fiber and none of the SHS sample met those
      recommendations. This cross-sectional study shows low adherence to ADA dietary
      recommendations for saturated fat, fiber, and sodium by American Indians with
      diabetes and by the broader U.S. population of adults with diabetes and shows
      that for American Indians with diabetes, programs to decrease SFA and increase
      fiber intakes are warranted.

PMID- 18716173
TI  - HIV infection is associated with decreased dietary diversity in South African
      children.
AB  - Little is known about dietary diversity of children residing in areas of high HIV
      prevalence. This study examined dietary diversity in 381 children ages 6-24 mo in
      rural South Africa. Twenty-eight (7.3%) children and 170 mothers (44.6%) were HIV
      infected. Home visits were conducted weekly and a detailed history of dietary
      intake obtained. A dietary diversity score was computed based on the weekly
      consumption of 8 food classes. Low dietary diversity was defined as falling
      within the lowest quartile of the diversity scale. There were 22,772 child weeks
      of observation: 1369 for HIV-infected children, 8876 for HIV-uninfected children
      born to HIV-infected mothers, and 12,527 for HIV-uninfected children born to HIV
      uninfected mothers. Low dietary diversity was more common in HIV-infected
      children [crude odds ratio (OR), 2.59; 95% CI, 1.52 to 4.41) compared with
      children born to HIV-uninfected mothers. In a multiple logistic regression
      analysis adjusting for socioeconomic and health status, HIV-infected children had
      lower dietary diversity (conditional OR, 1.76; 95% CI, 1.06 to 2.94) than HIV
      uninfected children. HIV-infected children consumed less in 6 of 8 food classes
      compared with HIV-uninfected children, with the 2 exceptions being breast milk
      and formula milk. In rural South Africa, HIV-infected children's diets are
      significantly less diverse than those of HIV-uninfected children. This may be a
      factor contributing to increased morbidity and poorer survival in these children.

PMID- 18716174
TI  - Short-chain fructooligosaccharides influence insulin sensitivity and gene
      expression of fat tissue in obese dogs.
AB  - Dietary fibers may modulate insulin resistance and glucose homeostasis in dogs.
      Their efficacy is, however, dependent on their origin, physical properties, and
      fermentability in the large bowel. Eight healthy Beagle dogs were fed a
      commercial diet at twice their maintenance requirements until they became obese.
      They were then maintained in the obese state and used in a cross-over design
      study to evaluate the effects of short-chain fructooligosaccharide (scFOS)
      supplementation (1% wt:wt dry matter in the diet). The euglycemic
      hyperinsulinemic clamp technique was performed before and after fattening and at
      the end of each 6-wk cross-over period. Fat tissue biopsies were taken in food
      deprived and postprandial phases to measure mRNA abundance of genes involved with
      fatty acid, glucose metabolism, or inflammation. Insulin resistance appeared
      progressively with fattening and the rate of glucose infusion during euglycemic
      clamp was lower (P < 0.05) at the end of the fattening period (7.39 mg.kg(
      1).min(-1)) than at baseline (21.21 mg.kg(-1).min(-1)). In stable obese dogs,
      scFOS increased (P < 0.05) the rate of glucose infusion compared with control
      (7.77 vs. 4.72 mg.kg(-1).min(-1)). Plasma insulin and triglyceride concentrations
      were greater in obese than in lean dogs but were not altered by scFOS. Whereas
      mRNA was not affected in food-deprived dogs, scFOS increased uncoupling protein 2
      (P = 0.05) and tended to increase carnitine palmitoyl transferase 1 adipose mRNA
      levels during the postprandial period (P = 0.09). Adding 1% scFOS to the diet of
      obese dogs decreases insulin resistance and appears to modulate the transcription
      of genes involved in fatty acid or glucose metabolism.

PMID- 18716175
TI  - An (n-3) polyunsaturated fatty acid-deficient diet disturbs daily locomotor
      activity, melatonin rhythm, and striatal dopamine in Syrian hamsters.
AB  - Several studies suggest that (n-3) PUFA may play a role in the regulation of
      cognitive functions, locomotor and exploratory activity, and affective disorders.
      Additionally, (n-3) PUFA affect pineal function, which is implicated in the sleep
      wake rhythm. However, no studies to our knowledge have explored the role of PUFA
      on the circadian system. We investigated the effect of an (n-3) PUFA-deficient
      diet on locomotor and pineal melatonin rhythms in Syrian hamsters used as model
      species in circadian rhythm research. To assess the possible relationship between
      voluntary wheel running activity and dopaminergic neurotransmission, we also
      measured endogenous monoamine concentrations in the striatum. Two-month-old male
      hamsters, fed either an (n-3) PUFA-deficient or an (n-3) PUFA-adequate diet, were
      housed individually in cages equipped with run wheels. At 3 mo, cerebral
      structures were extracted for biochemical and cellular analysis. In (n-3) PUFA
      deficient hamsters, the induced changes in the pineal PUFA membrane phospholipid
      composition were associated with a reduction in the nocturnal peak level of
      melatonin that was 52% lower than in control hamsters (P < 0.001). The (n-3) PUFA
      deficient hamsters also had higher diurnal (P < 0.01) and nocturnal (P = 0.001)
      locomotor activity than the control hamsters, in parallel with activation of
      striatal dopaminergic function (P < 0.05). The (n-3) PUFA-deficient hamsters
      exhibited several symptoms: chronic locomotor hyperactivity, disturbance in
      melatonin rhythm, and striatal hyperdopaminergia. We suggest that an (n-3) PUFA
      deficient diet lessens the melatonin rhythm, weakens endogenous functioning of
      the circadian clock, and plays a role in nocturnal sleep disturbances as
      described in attention deficit/hyperactivity disorder.

PMID- 18716176
TI  - A population's mean Healthy Eating Index-2005 scores are best estimated by the
      score of the population ratio when one 24-hour recall is available.
AB  - The USDA Healthy Eating Index-2005 (HEI-2005) is a tool to quantify and evaluate
      the quality of diet consumed by the U.S. population. It comprises 12 components,
      expressed as ratios of a food group or nutrient to energy intake. The components
      are scored on a scale from 0 to M, where M is 5, 10, or 20. Ideally, the HEI-2005
      is calculated on the basis of the usual dietary intake of an individual. Intake
      data, collected via a 24-h recall, are often available for only 1 d for each
      individual. In this article, we examine how best to estimate a population's mean
      usual HEI-2005 component and total scores when 1 d of dietary information is
      available for a sample of individuals from the population. Three methods are
      considered: the mean of individual scores, the score of the mean of individual
      ratios, and the score of the ratio of total food group or nutrient intake to
      total energy intake, which we call the population ratio. We investigate via
      computer simulation which method is the least biased. The simulations are based
      on statistical modeling of the distributions of intakes reported by 738 women
      participating in the Eating at America's Table Study. The results show that
      overall, the score of the population ratio is the preferred method. We therefore
      recommend that the quality of the U.S. population's diet be assessed and
      monitored using this method.

PMID- 18716177
TI  - Second International Nuts and Health Symposium, 2007: introduction.

PMID- 18716178
TI  - Tree nuts and peanuts as components of a healthy diet.
AB  - Nuts have been part of the diet for thousands of years. In 2003, a Qualified
      Health Claim was approved, stating that eating 1.5 oz (42 g) of nuts per day may
      reduce the risk of heart disease. Usual intakes fall short of this
      recommendation. About one-third of Americans report consuming nuts (tree nuts or
      peanuts) on any one day. Seven percent of Europeans report eating nuts, but the
      amount eaten by European nut consumers (31 g/d) is larger than that of Americans
      (21 g/d). Nuts are an excellent source of vitamin E and magnesium. Individuals
      consuming nuts also have higher intakes of folate, beta-carotene, vitamin K,
      lutein+zeaxanthin, phosphorus, copper, selenium, potassium, and zinc per 1000
      kcal. Regular nut consumption increases total energy intake by 250 kcal/d (1.05
      MJ/d), but the body weight of nut consumers is not greater than that of
      nonconsumers. Nuts are an excellent source of phytochemicals (phyotsterols,
      phenolic acids, flavonoids, stilbenes, and carotenoids). The total phenolic
      constituents probably contribute to the total antioxidant capacity of nuts, which
      is comparable to broccoli and tomatoes. To improve guidance on the use of nuts in
      the diet, the position of nuts in typical food patterns needs to be addressed.
      The 2005 MyPyramid includes nuts in the meat and beans group. Yet, nuts are
      rarely consumed as meat substitutes. Because approximately 60% of the nuts
      consumed in the U.S. are eaten as snacks, emphasizing their use as a healthy
      snack may be more effective than inclusion within a food group.

PMID- 18716179
TI  - Impact of peanuts and tree nuts on body weight and healthy weight loss in adults.
AB  - Nuts (ground and tree) are rich sources of multiple nutrients and their
      consumption is associated with health benefits, including reduced cardiovascular
      disease risk. This has prompted recommendations to increase their consumption.
      However, they are also high in fat (albeit largely unsaturated) and are energy
      dense. The associations between these properties, positive energy balance, and
      body weight raise questions about such recommendations. This issue is addressed
      through a review of the literature pertaining to the association between nut
      consumption and energy balance. Epidemiological studies document an inverse
      association between the frequency of nut consumption and BMI. Clinical trials
      reveal little or no weight change with inclusion of various types of nuts in the
      diet over 1-6 mo. Mechanistic studies indicate this is largely attributable to
      the high satiety property of nuts, leading to compensatory responses that account
      for 65-75% of the energy they provide. Limited data suggest chronic consumption
      is associated with elevated resting energy expenditure resulting in dissipation
      of another portion of the energy they provide. Additionally, due to poor
      bioaccessibility, there is limited efficiency of energy absorption from nuts.
      Collectively, these mechanisms offset much of the energy provided by nuts. The
      few trials contrasting weight loss through regimens that include or exclude nuts
      indicate improved compliance and greater weight loss when nuts are permitted.
      This consistent literature suggests nuts may be included in the diet, in
      moderation, to enhance palatability and nutrient quality without posing a threat
      for weight gain.

PMID- 18716180
TI  - The role of tree nuts and peanuts in the prevention of coronary heart disease:
      multiple potential mechanisms.
AB  - Epidemiologic and clinical trial evidence has demonstrated consistent benefits of
      nut and peanut consumption on coronary heart disease (CHD) risk and associated
      risk factors. The epidemiologic studies have reported various endpoints,
      including fatal CHD, total CHD death, total CHD, and nonfatal myocardial infarct.
      A pooled analysis of 4 U.S. epidemiologic studies showed that subjects in the
      highest intake group for nut consumption had an approximately 35% reduced risk of
      CHD incidence. The reduction in total CHD death was due primarily to a decrease
      in sudden cardiac death. Clinical studies have evaluated the effects of many
      different nuts and peanuts on lipids, lipoproteins, and various CHD risk factors,
      including oxidation, inflammation, and vascular reactivity. Evidence from these
      studies consistently shows a beneficial effect on these CHD risk factors. The LDL
      cholesterol-lowering response of nut and peanut studies is greater than expected
      on the basis of blood cholesterol-lowering equations that are derived from
      changes in the fatty acid profile of the diet. Thus, in addition to a favorable
      fatty acid profile, nuts and peanuts contain other bioactive compounds that
      explain their multiple cardiovascular benefits. Other macronutrients include
      plant protein and fiber; micronutrients including potassium, calcium, magnesium,
      and tocopherols; and phytochemicals such as phytosterols, phenolic compounds,
      resveratrol, and arginine. Nuts and peanuts are food sources that are a composite
      of numerous cardioprotective nutrients and if routinely incorporated in a healthy
      diet, population risk of CHD would therefore be expected to decrease markedly.

PMID- 18716181
TI  - Possible benefit of nuts in type 2 diabetes.
AB  - Nuts, including peanuts, are now recognized as having the potential to improve
      the blood lipid profile and, in cohort studies, nut consumption has been
      associated with a reduced risk of coronary heart disease (CHD). More recently,
      interest has grown in the potential value of including nuts in the diets of
      individuals with diabetes. Data from the Nurses Health Study indicates that
      frequent nut consumption is associated with a reduced risk of developing diabetes
      and cardiovascular disease. Randomized controlled trials of patients with type 2
      diabetes have confirmed the beneficial effects of nuts on blood lipids also seen
      in nondiabetic subjects, but the trials have not reported improvement in A1c or
      other glycated proteins. Acute feeding studies, however, have demonstrated the
      ability of nuts, when eaten with carbohydrate (bread), to depress postprandial
      glycemia. Furthermore, there was evidence of reduced postprandial oxidative
      stress associated with nut consumption. In terms of dietary composition, nuts
      have a good nutritional profile, are high in monounsaturated fatty acids (MUFA)
      and PUFA, and are good sources of vegetable protein. Incorporation of nuts in the
      diet may therefore improve the overall nutritional quality of the diet. We
      conclude that there is justification to consider the inclusion of nuts in the
      diets of individuals with diabetes in view of their potential to reduce CHD risk,
      even though their ability to influence overall glycemic control remains to be
      established.

PMID- 18716182
TI  - Tree nut and peanut consumption in relation to chronic and metabolic diseases
      including allergy.
AB  - The New and Emerging Research session highlighted the emerging understanding of
      both the positive and negative effects of nuts consumption on health. The limited
      nature of both experimental and epidemiological evidence for positive
      relationship(s) between nut intake and health were noted. Study inconsistency and
      limitations, particularly survey methodology, were explored. Recent results from
      epidemiologic studies indicating a potential negative association between nut and
      seed intake and cancer risk were reviewed. The ability of walnuts to reduce
      endothelin suggests an interesting biochemical mechanism of nut action that may
      affect other endothelin-associated diseases, which should be further explored.
      The effects of nuts and their constituents on a nuclear receptor screen
      (PPARalpha, beta/delta, gamma, LXRalpha, beta, RXRalpha, beta, gamma, PXR, and
      FXR) have been explored. Nut allergenicity and approaches necessary to minimize
      this effect were also described. In contrast to the positive effects, nut
      allergies present tree nut-allergic consumers with health challenges. The Food
      Allergy and Anaphylaxis Network stressed the importance of ensuring that
      consumers with food allergies have legible, accurate food labels. The Food
      Allergen Labeling and Consumer Protection Act has engendered precautionary, worst
      case allergen scenario labeling statements with unknown benefits to consumer
      health. Issues of cross-contamination due to shared equipment and shared
      facilities highlighted the need to rely on allergen control programs that use
      ELISA technology and have increased understanding of nut allergens. Ultimately,
      to maximize the positive benefits of nuts, the consumer must be provided with all
      the information required to make an informed choice.

PMID- 18716183
TI  - Priority areas for research on the intake, composition, and health effects of
      tree nuts and peanuts.
AB  - This article summarizes the main conclusions drawn from a conference on the
      health effects of nut consumption and identifies priority areas for future
      research. Individuals with higher intakes of nuts generally have higher intakes
      of many beneficial dietary constituents. More information is needed on nut
      composition, the bioavailability of nutrients, and other bioactive constituents.
      Better methods are needed to assess usual nut intake, including biomarkers, and
      the types, physical form, and amounts of nuts that are consumed. The feasibility
      of including nuts and seeds as a separate food group in the Dietary Guidelines
      should be tested, as should ways to increase nut intake. A moderate intake of
      nuts can be included in a weight loss regimen and further information is needed
      on whether nuts improve satiety as well as adherence to and efficacy of diets
      designed for weight reduction. There is substantial evidence that nut consumption
      reduces risk of cardiovascular disease. Future research should investigate their
      benefits for prevention of congestive heart failure, including clinical studies
      in patients with this condition, to evaluate the effects of nuts on markers of
      heart disease risk. Higher nut consumption is associated with lower risk of
      diabetes and associated cardiovascular disease. More remains to be learned about
      the effects of nuts on postprandial glycemic and insulin response, glycemic
      control, and improvement of disease risk factors in subjects with prediabetes and
      diabetes. Information is needed on nut-induced allergic reactions, including
      their prevalence and consequences, causes of sensitization, biomarkers of severe
      reactions, and cross-reactivity to different types of nuts.

PMID- 18716184
TI  - Dietary influences on infection and allergy in infants: introduction.

PMID- 18716185
TI  - Strategies for atopy prevention.
AB  - Allergic diseases, particularly in childhood, have become one of the epidemics of
      the 21st century. Whereas previous strategies for allergy prevention focused on
      the avoidance of risk factors, more recent approaches are addressing attempts to
      provide protective factors to infants and young children to achieve immune
      modulation and tolerance to harmless nutritional or environmental allergens. This
      change of paradigm for allergy prevention might lead to more effective
      interventions, which hopefully contribute to reversing the epidemiologic trend of
      the last decades. In many industrialized countries, the increased prevalence of
      atopy and asthma has become a serious public health issue. If preventive
      intervention could be effective at all, it would have to be applied early in
      life, most probably in early infancy. Unfortunately, our understanding of the
      natural history of the process of atopic sensitization, atopic dermatitis, and
      allergic airway disease is still very limited. On the other hand, the evaluation
      of risk factors and determinants is a necessary prerequisite for any effective
      intervention.

PMID- 18716186
TI  - The maturation of the fetal and neonatal immune system.
AB  - The prevalence of allergic diseases has risen markedly since the 1960s,
      particularly in the developed countries of the Western world. These diseases
      manifest initially during infancy and childhood and are apparently becoming more
      persistent in successive birth cohorts. The importance of genetic susceptibility
      in the disease process is widely recognized, and it is further recognized that
      the ultimate expression of the disease is the result of complex interactions
      between genetic and environmental factors, with nutrition representing 1 main
      variable, neither of which have yet been comprehensively characterized. There is
      increasing evidence that the level of complexity inherent in the pathogenesis of
      allergic diseases may be even greater than is currently contemplated, as an
      additional set of crucial factors appear to be involved. Notably, it appears
      likely that the ultimate effects of the "gene-environment" interaction within
      individuals may also be related to the developmental status of the relevant
      target tissues at the time the interactions occur. Examples of the latter,
      discussed below, are elements of innate and adaptive immune function and aspects
      of food allergy and of airway function relevant to atopic asthma.

PMID- 18716187
TI  - Breast-feeding and its role in early development of the immune system in infants:
      consequences for health later in life.

PMID- 18716188
TI  - Postnatal development of intestinal microflora as influenced by infant nutrition.
AB  - The postnatal period of a new human being is characterized, from the
      microbiological point of view, by the formation of a new ecosystem: the
      microflora of the human gut. In adulthood a number of barriers exert a potent
      selective action on bacteria arriving from the mouth, but in the very first stage
      of our life, these barriers are kept at a very low level, temporarily allowing
      penetration into the gut of bacteria that are not really believed to be "gut
      related." Moreover, type of delivery (natural vs. cesarean) and feeding (breast
      vs. bottle feeding) play dramatic roles in determining the microflora
      composition. In the last decade a number of articles have reported results on
      neonates' microflora obtained by means of culture-independent analysis. Data
      obtained by means of these techniques are in agreement with those produced by
      selective media, but they also provide some new insights about the presence of
      anaerobic bacteria. The focus of this article is to update knowledge on infants'
      microflora during the first 6 mo of life.

PMID- 18716189
TI  - Cesarean delivery may affect the early biodiversity of intestinal bacteria.
AB  - The gastrointestinal tract of neonates becomes colonized immediately after birth
      with environmental microorganisms, mainly from the mother; strong evidence
      suggests that the early composition of the microbiota of neonates plays an
      important role for the postnatal development of the immune system. The present
      study was designed to evaluate by means of a molecular biology approach the
      relation between the intestinal ecosystem of the newborn and the mode of
      delivery. The intestinal bacterial composition on d 3 of life was investigated in
      23 infants born by vaginal delivery and in 23 infants delivered by cesarean
      section. PCR-denaturing gradient gel electrophoresis and PCR-temperature gradient
      gel electrophoresis have been utilized, together with the specific amplifications
      for 10 Bifidobacterium species, 3 Ruminococcus species, and Bacteroides. The
      intestinal microbiota of neonates delivered by cesarean delivery appears to be
      less diverse, in terms of bacteria species, than the microbiota of vaginally
      delivered infants. The intestinal microbiota after cesarean delivery is
      characterized by an absence of Bifidobacteria species. Vaginally delivered
      neonates, even if they showed individual microbial profiles, were characterized
      by predominant groups such as B. longum and B. catenulatum. Our data demonstrate
      that the mode of delivery has a deep impact on the composition of the intestinal
      microbiota at the very beginning of human life. This study opens the path to
      further investigations to confirm the link between microbiota composition and
      immune system development and to identify tools for the modulation of the
      intestinal microbiota of cesarean-delivered neonates. Additionally, we underline
      the importance of adequate microbiological tools used to support clinically
      relevant trials, if intestinal microbiota is considered as a study outcome.

PMID- 18716190
TI  - Antiinfective properties of human milk.
AB  - The unfavorable effects of neonatal immunodeficiency are limited by some
      naturally occurring compensatory mechanisms, such as the introduction of
      protective and immunological components of human milk in the infant. Breast
      feeding maintains the maternal-fetal immunological link after birth, may favor
      the transmission of immunocompetence from the mother to her infant, and is
      considered an important contributory factor to the neonatal immune defense system
      during a delicate and crucial period for immune development. Several studies have
      reported that breast-feeding, because of the antimicrobial activity against
      several viruses, bacteria, and protozoa, may reduce the incidence of infection in
      infants. The protection from infections may be ensured either passively by
      factors with antiinfective, hormonal, enzymatic, trophic, and bioactive activity
      present in breast milk, or through a modulator effect on the neonatal immune
      system exerted by cells, cytokines, and other immune agents in human milk.

PMID- 18716191
TI  - Long-chain polyunsaturated fatty acids influence the immune system of infants.
AB  - Several events occur during the first months of life that allow the immune system
      to become competent and functional. The aim of this article is to review the
      rationale and evidence of an influence of (n-3) long-chain PUFA (LCPUFA) on the
      immune system of infants. The (n-3) LCPUFA exert their immunomodulatory
      activities at different levels. The (n-3) LCPUFA metabolites induce eicosanoid
      production, alter gene expression, and modify lipid raft composition, altering T
      cell signaling; all contribute to immunological functional changes. However, the
      roles of these mechanisms and the types of T or other immunological cells
      involved remain unclear at present. Moreover, the effect of (n-3) LCPUFA on the
      immune system of infants may vary according to dose, time of exposure, and
      profile of the immune system (T-helper, Th1/Th2). Most of the interventional
      studies in infancy have been performed for the prevention of allergy. They all
      confirmed influence on T-cell function and cytokine profiles, but clinically
      beneficial effects are more conflicting. Supplementation of the maternal diet in
      pregnancy or early childhood with (n-3) LCPUFA is potentially a noninvasive
      intervention strategy to prevent the development of allergy, infection, and
      possibly other immune-mediated diseases. However, any long-term in vivo effects
      on (n-3) LCPUFA early in life for immunomodulatory defense in infants and later
      on immune status and health remain to be assessed.

PMID- 18716192
TI  - Nutritional factors influencing infections in preterm infants.
AB  - In contrast with clinical studies in term infants or older children, it is very
      difficult to investigate possible immunoregulatory effects of a novel infant
      formula composition in preterm infants. This is mainly because of the multicausal
      origin of infections in this high-risk population that is usually admitted to the
      neonatal intensive care unit. Possible effects of nutrition composition on onset
      and incidence of nosocomial infections in these very small infants have to be
      compared with infections that may have originated in utero. The development of
      the gastrointestinal tract may be inhibited after severe intrauterine growth
      retardation, leading to functional impairment of the gut shortly after birth.
      This may be related to the onset of necrotizing enterocolitis of the newborn.
      However, this disease in very small preterm infants is possibly also related to
      the initiation of oral feeding and/or the amount of feeding. Specific infection
      risks of neonatal intensive care as a result of invasive techniques such as
      artificial ventilation or total parenteral nutrition using indwelling umbilical
      and/or Silastic lines and so-called "all-in-one" mixtures may influence the
      incidence of infections. Widespread use of intravenous antibiotics in the
      neonatal intensive care unit may create an even larger infection risk.
      Investigation of possible immunomodulatory effects of factors such as prebiotics
      and probiotics added to the nutrition of preterm infants should always be
      considered along with other nutritional factors known to influence the immature
      immune system.

PMID- 18716193
TI  - Structural and functional aspects of prebiotics used in infant nutrition.
AB  - Breast-feeding is associated with several benefits. Among them, the balanced
      postnatal development of the immune system is 1 of the key functions of breast
      feeding. Although this effect is of multifactorial origin, it is widely accepted
      that the entire intestinal microbiota of breast-fed infants represents an
      important stimulating factor of the postnatal development of the immune system.
      The effect of breast-feeding on the intestinal microbiota can not be attributed
      to a single compound, but there is accumulating evidence that human milk
      oligosaccharides play a crucial role. Because there is a broad consensus that the
      intestinal microbiota plays an important physiological role for the host, many
      attempts have been made to influence the intestinal flora by dietary
      interventions. This article summarizes results of intervention studies in which
      nonmilk oligosaccharides have been used to mimic the prebiotic effect of breast
      feeding. A second focus has been related to the question of whether the prebiotic
      activity has beneficial effects on the postnatal development of the immune
      system. The data clearly demonstrate that prebiotics of nonmilk origin can mimic
      the prebiotic effect of breast-feeding, and this has positive consequences for
      the postnatal development of the immune system.

PMID- 18716194
TI  - The impact of enteral insulin-like growth factor 1 and nutrition on gut
      permeability and amino acid utilization.
AB  - The intestine serves numerous purposes. In addition to digestion and absorption,
      the intestine functions as an organ that provides specific and nonspecific
      protection against pathological bacteria and noxious agents. At birth, and
      certainly when birth occurs prematurely, these functions are not yet fully
      developed. This article addresses the specific needs of the neonatal gut to
      perform these functions adequately and describes efforts to modulate intestinal
      barrier function by preterm formula supplemented with insulin-like growth factor
      1.

PMID- 18716195
TI  - Dissociating the effects of past and future on neural encoding of sequences in
      the hippocampus.

PMID- 18716196
TI  - Does chronic remyelination occur for all spared axons after spinal cord injury in
      mouse?

PMID- 18716197
TI  - Dissociable roles for cortical and subcortical structures in memory retrieval and
      acquisition.
AB  - The relationship between anterograde and retrograde amnesia remains unclear.
      Previous data from both clinical neuropsychology and monkey lesion studies
      suggest that damage to discrete subcortical structures leads to a relatively
      greater degree of anterograde than retrograde amnesia, whereas damage to discrete
      regions of cortex leads to the opposite pattern of impairments. Nevertheless,
      damage to the medial diencephalon in humans is associated with both retrograde
      and anterograde amnesia. In the present study, we sought to reconcile this by
      assessing retention as well as subsequent relearning and new postoperative
      learning. Rhesus monkeys learned 300 unique scene discriminations preoperatively,
      and retention was assessed in a preoperative and postoperative one-trial
      retrieval test. Combined bilateral subcortical lesions to the magnocellular
      mediodorsal thalamus and fornix impaired postoperative retention of the
      preoperatively acquired information. In addition, subsequent relearning and new
      postoperative learning were also impaired. This contrasts with the effects of a
      discrete lesion to just one of these structures, after which retention is intact
      in both cases. Discrete bilateral ablations to the entorhinal cortex impaired
      retention but had no effect on new learning. Combined with previous work from our
      laboratory, these results support the hypothesis that subcortical damage has a
      relatively greater effect on new learning, and cortical damage has a relatively
      greater effect on retention. Furthermore, the results demonstrate that retrograde
      amnesia occurs as a result of subcortical damage only if it is widespread,
      leading to an extensive disruption of cortical functioning. Damage of this nature
      may account for dense amnesia.

PMID- 18716198
TI  - Gamma-band activity in human posterior parietal cortex encodes the motor goal
      during delayed prosaccades and antisaccades.
AB  - Although it is well established that parietal cortex is important in processing
      sensorimotor transformations, less is known about the neuronal dynamics of this
      process in humans. Using magnetoencephalography, we investigated the dynamics of
      parietal oscillatory activity during saccade planning in terms of sensory and
      motor goal processing. In the experiments, a peripheral stimulus was flashed in
      either the left or right hemifield, followed by a 1.5 s delay period, after which
      the subject executed a saccade toward (prosaccade) or away from (antisaccade) the
      stimulus. In response to stimulus presentation, we observed an initial increase
      in gamma-band power (40-120 Hz) in a region in the posterior parietal cortex
      contralateral to the direction of the stimulus. This lateralized power
      enhancement, which was sustained in a more narrow frequency band (85-105 Hz)
      during the delay period of prosaccades, mapped to the hemisphere contralateral to
      the direction of the saccade goal during the delay period of antisaccades. These
      results suggest that neuronal gamma-band synchronization in parietal cortex
      represents the planned direction of the saccade, not the memorized stimulus
      location. In the lower-frequency bands, we observed sustained contralateral alpha
      (7-13 Hz) power suppression after stimulus presentation in parieto-occipital
      regions. The dynamics of the alpha band was strongly related to the processing of
      the stimulus and showed only modest selectivity for the goal of the saccade. We
      conclude that parietal gamma-band synchronization reflects a mechanism to encode
      the motor goals in the visuomotor processing for saccades.

PMID- 18716199
TI  - Dissociation between rewarding and psychomotor effects of opiates: differential
      roles for glutamate receptors within anterior and posterior portions of the
      ventral tegmental area.
AB  - The rewarding effects of drugs of abuse are thought to be dependent on the
      mesocorticolimbic dopamine system, which originates in the ventral tegmental area
      (VTA) and projects into the nucleus accumbens (NAC) and other forebrain regions.
      Heroin, by inhibiting GABAergic interneurons in the VTA, induces local
      dopaminergic activation and release in the NAC terminals. The role of other basic
      neurotransmitter systems, such as glutamate in the VTA, in mediating the
      rewarding effect of addictive drugs, is less established. We explored whether
      blockade of glutamate receptors in subregions of the VTA modulate the rewarding
      properties and/or the development of psychomotor changes induced by opiates.
      Administration of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; an AMPA/kainate
      receptor antagonist) into the anterior VTA blocked the rewarding effects of
      opiates in both the conditioned place preference and the self-administration
      paradigms without affecting the gradual increase of the psychomotor response to
      opiates. In contrast, administration of CNQX into the posterior VTA did not
      affect the rewarding properties of opiates, but blocked the initial sedative
      effect of opiates and the gradual increase of the psychomotor response to the
      drug. These findings suggest a critical role for glutamate receptors in the VTA
      in opiate reward, as well as behavioral and anatomical dissociation between the
      rewarding and psychomotor effects of opiates.

PMID- 18716200
TI  - Dynamic premotor-to-parietal interactions during spatial imagery.
AB  - The neurobiological processes underlying mental imagery are a matter of debate
      and controversy among neuroscientists, cognitive psychologists, philosophers, and
      biologists. Recent neuroimaging studies demonstrated that the execution of mental
      imagery activates large frontoparietal and occipitotemporal networks in the human
      brain. These previous imaging studies, however, neglected the crucial interplay
      within and across the widely distributed cortical networks of activated brain
      regions. Here, we combined time-resolved event-related functional magnetic
      resonance imaging with analyses of interactions between brain regions (functional
      and effective brain connectivity) to unravel the premotor-parietal dynamics
      underlying spatial imagery. Participants had to sequentially construct and
      spatially transform a mental visual object based on either verbal or visual
      instructions. By concurrently accounting for the full spatiotemporal pattern of
      brain activity and network connectivity, we functionally segregated an early from
      a late premotor-parietal imagery network. Moreover, we revealed that the modality
      specific information upcoming from sensory brain regions is first sent to the
      premotor cortex and then to the medial-dorsal parietal cortex, i.e., top-down
      from the motor to the perceptual pole during spatial imagery. Importantly, we
      demonstrate that the premotor cortex serves as the central relay station,
      projecting to parietal cortex at two functionally distinct stages during spatial
      imagery. Our approach enabled us to disentangle the multicomponential cognitive
      construct of mental imagery into its different cognitive subelements. We discuss
      and explicitly assign these mental subprocesses to each of the revealed effective
      brain connectivity networks and present an integrative neurobiological model of
      spatial imagery.

PMID- 18716201
TI  - Role of Dickkopf-1, an antagonist of the Wnt/beta-catenin signaling pathway, in
      estrogen-induced neuroprotection and attenuation of tau phosphorylation.
AB  - 17beta-Estradiol (E2) has been implicated to be neuroprotective in a variety of
      neurodegenerative disorders, although the mechanism remains poorly understood.
      The current study sheds light on this issue by demonstrating that low
      physiological levels of E2 protects the hippocampus CA1 against global cerebral
      ischemia by preventing elevation of dickkopf-1 (Dkk1), an antagonist of the
      Wnt/beta-catenin signaling pathway, which is a principal mediator of
      neurodegeneration in cerebral ischemia and Alzheimer's disease. E2 inhibition of
      Dkk1 elevation correlated with a reduction of phospho-beta-catenin and elevation
      of nuclear beta-catenin levels, as well as enhancement of Wnt-3, suggesting E2
      activation of the Wnt/beta-catenin signaling pathway. In agreement, the beta
      catenin downstream prosurvival factor, survivin, was induced by E2 at 24 and 48 h
      after cerebral ischemia, an effect observed only in surviving neurons because
      degenerating neurons lacked survivin expression. E2 suppression of Dkk1 elevation
      was found to be caused by attenuation of upstream c-Jun N-terminal protein kinase
      (JNK)/c-Jun signaling, as E2 attenuation of JNK/c-Jun activation and a JNK
      inhibitor significantly blocked Dkk1 induction. Tau hyperphosphorylation has been
      implicated to have a prodeath role in Alzheimer's disease and cerebral ischemia,
      and E2 attenuates tau hyperphosphorylation. Our study demonstrates that tau
      hyperphosphorylation is strongly induced after global cerebral ischemia, and that
      E2 inhibits tau hyperphosphorylation by suppressing activation of the JNK/c
      Jun/Dkk1 signaling pathway. Finally, exogenous Dkk1 replacement via
      intracerebroventricular administration completely reversed E2-induced
      neuroprotection, nuclear beta-catenin induction, and phospho-tau attenuation,
      further suggesting that E2 inhibition of Dkk1 is a critical mechanism underlying
      its neuroprotective and phospho-tau regulatory effects after cerebral ischemia.

PMID- 18716202
TI  - Specificity of afferent synapses onto plane-polarized hair cells in the posterior
      lateral line of the zebrafish.
AB  - The proper wiring of the vertebrate brain represents an extraordinary
      developmental challenge, requiring billions of neurons to select their
      appropriate synaptic targets. In view of this complexity, simple vertebrate
      systems provide necessary models for understanding how synaptic specificity
      arises. The posterior lateral-line organ of larval zebrafish consists of
      polarized hair cells organized in discrete clusters known as neuromasts. Here we
      show that each afferent neuron of the posterior lateral line establishes specific
      contacts with hair cells of the same hair-bundle polarity. We quantify this
      specificity by modeling the neuron as a biased selector of hair-cell polarity and
      find evidence for bias from as early as 2.5 d after fertilization. More than half
      of the neurons form contacts on multiple neuromasts, but the innervated organs
      are spatially consecutive and the polarity preference is consistent. Using a
      novel reagent for correlative electron microscopy, HRP-mCherry, we show that
      these contacts are indeed afferent synapses bearing vesicle-loaded synaptic
      ribbons. Moreover, afferent neurons reassume their biased innervation pattern
      after hair-cell ablation and regeneration. By documenting specificity in the
      pattern of neuronal connectivity during development and in the context of organ
      regeneration, these results establish the posterior lateral-line organ as a
      vertebrate system for the in vivo study of synaptic target selection.

PMID- 18716203
TI  - Sleep deprivation decreases binding of [11C]raclopride to dopamine D2/D3
      receptors in the human brain.
AB  - Sleep deprivation did not affect dopamine transporters (target for most wake
      promoting medications) and thus dopamine increases are likely to reflect
      increases in dopamine cell firing and/or release rather than decreases in
      dopamine reuptake. Because dopamine-enhancing drugs increase wakefulness, we
      postulate that dopamine increases after sleep deprivation is a mechanism by which
      the brain maintains arousal as the drive to sleep increases but one that is
      insufficient to counteract behavioral and cognitive impairment. Sleep deprivation
      can markedly impair human performance contributing to accidents and poor
      productivity. The mechanisms underlying this impairment are not well understood,
      but brain dopamine systems have been implicated. Here, we test whether one night
      of sleep deprivation changes dopamine brain activity. We studied 15 healthy
      subjects using positron emission tomography and [11C]raclopride (dopamine D2/D3
      receptor radioligand) and [11C]cocaine (dopamine transporter radioligand).
      Subjects were tested twice: after one night of rested sleep and after one night
      of sleep deprivation. The specific binding of [11C]raclopride in the striatum and
      thalamus were significantly reduced after sleep deprivation and the magnitude of
      this reduction correlated with increases in fatigue (tiredness and sleepiness)
      and with deterioration in cognitive performance (visual attention and working
      memory). In contrast, sleep deprivation did not affect the specific binding of
      [11C]cocaine in the striatum. Because [11C]raclopride competes with endogenous
      dopamine for binding to D2/D3 receptors, we interpret the decreases in binding to
      reflect dopamine increases with sleep deprivation. However, we cannot rule out
      the possibility that decreased [11C]raclopride binding reflects decreases in
      receptor levels or affinity. Sleep deprivation did not affect dopamine
      transporters (target for most wake-promoting medications) and thus dopamine
      increases are likely to reflect increases in dopamine cell firing and/or release
      rather than decreases in dopamine reuptake. Because dopamine-enhancing drugs
      increase wakefulness, we postulate that dopamine increases after sleep
      deprivation is a mechanism by which the brain maintains arousal as the drive to
      sleep increases but one that is insufficient to counteract behavioral and
      cognitive impairment.

PMID- 18716204
TI  - Dopaminergic D1 and D2 receptors are essential for the arousal effect of
      modafinil.
AB  - Modafinil is a wake-promoting compound with low abuse potential used in the
      treatment of narcolepsy. Although the compound is reported to affect multiple
      neurotransmitter systems such as catecholamines, serotonin, glutamate, GABA,
      orexin, and histamine, however, the molecular mechanism by which modafinil
      increases wakefulness is debated. Herein we used dopamine (DA) D(2) receptor
      (D(2)R)-deficient mice combined with D(1)R- and D(2)R-specific antagonists to
      clarify the role of DA receptors in the arousal effects of modafinil. In wild
      type mice, intraperitoneal modafinil induced wakefulness in a dose-dependent
      manner. Pretreatment with either D(1)R antagonist SCH23390 [R-(+)-7-chloro-8
      hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine] at 30 microg/kg or
      D(2)R antagonist raclopride at 2 mg/kg blocked the arousal effects of low-dose
      modafinil at 22.5 and 45 mg/kg. When modafinil was given at 90 and 180 mg/kg,
      pretreatment of D(1)R antagonist did not affect the wakefulness at all, whereas
      D(2)R antagonist significantly attenuated the wakefulness to the half level
      compared with vehicle control. Similarly, D(2)R knock-out (KO) mice exhibited
      attenuated modafinil-induced wakefulness. However, pretreatment of D(2)R KO mice
      with D(1)R antagonist completely abolished arousal effects of modafinil. These
      findings strongly indicate that dopaminergic D(1)R and D(2)R are essential for
      the wakefulness induced by modafinil.

PMID- 18716205
TI  - A fast mode of membrane fusion dependent on tight SNARE zippering.
AB  - SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)
      proteins have a key role in membrane fusion. It is commonly assumed that pairing
      of SNARE proteins anchored in opposing membranes overcomes the repulsion energy
      between membranes, thereby catalyzing fusion. In this study, we have increased
      the distance between the coiled-coil SNARE motif and the transmembrane domain of
      the vesicular SNARE synaptobrevin-2 by insertion of a flexible linker to analyze
      how an increased intermembrane distance affects exocytosis. Synaptobrevin-2
      lengthening did not change the frequency of exocytotic events measured at 1 mum
      free calcium but prevented the increase in the secretory activity triggered by
      higher calcium concentration. Exocytotic events monitored in adrenal chromaffin
      cells by means of carbon fiber amperometry were classified in two groups
      according to the rate and extent of fusion pore expansion. Lengthening the
      juxtamembrane region of synaptobrevin-2 severely reduced the occurrence of rapid
      single events, leaving slow ones unchanged. It also impaired the increase in the
      fast-fusion mode that normally follows elevation of intracellular Ca2+ levels. We
      conclude that mild stimuli trigger slow fusion events that do not rely on a short
      intermembrane distance. In contrast, a short intermembrane distance mediated by
      tight zippering of SNAREs is essential to a component of the secretory response
      elicited by robust stimuli and characterized by rapid dilation of the fusion
      pore.

PMID- 18716206
TI  - Structural plasticity of circuits in cortical neuropil.
AB  - Learning and memory formation in the brain depend on the plasticity of neural
      circuits. In the adult and developing cerebral cortex, this plasticity can result
      from the formation and elimination of dendritic spines. New synaptic contacts
      appear in the neuropil where the gaps between axonal and dendritic branches can
      be bridged by dendritic spines. Such sites are termed potential synapses. Here,
      we describe a theoretical framework for the analysis of spine remodeling
      plasticity. We provide a quantitative description of two models of spine
      remodeling in which the presence of a bouton is either required or not for the
      formation of a new synapse. We derive expressions for the density of potential
      synapses in the neuropil, the connectivity fraction, which is the ratio of actual
      to potential synapses, and the number of structurally different circuits
      attainable with spine remodeling. We calculate these parameters in mouse
      occipital cortex, rat CA1, monkey V1, and human temporal cortex. We find that, on
      average, a dendritic spine can choose among 4-7 potential targets in rodents and
      10-20 potential targets in primates. The potential of neuropil for structural
      circuit remodeling is highest in rat CA1 (7.1-8.6 bits/mum(3)) and lowest in
      monkey V1 (1.3-1.5 bits/mum(3)). We also evaluate the lower bound of neuron
      selectivity in the choice of synaptic partners. Postsynaptic excitatory neurons
      in rodents make synaptic contacts with >21-30% of presynaptic axons encountered
      with new spine growth. Primate neurons appear to be more selective, making
      synaptic connections with >7-15% of encountered axons.

PMID- 18716207
TI  - Differential implication of proinflammatory cytokine interleukin-6 in the
      development of cephalic versus extracephalic neuropathic pain in rats.
AB  - Responses resulting from injury to the trigeminal nerve exhibit differences
      compared with those caused by lesion of other peripheral nerves. With the aim of
      elucidating the physiopathological mechanisms underlying cephalic versus
      extracephalic neuropathic pain, we determined the time course expression of
      proinflammatory cytokines interleukin-6 (IL-6) and IL-1beta, neuronal injury
      (ATF3), macrophage/microglial (OX-42), and satellite cells/astrocyte (GFAP)
      markers in central and ganglion tissues in rats that underwent unilateral chronic
      constriction injury (CCI) to either infraorbital nerve (IoN) (cephalic area) or
      sciatic nerve (SN) (extracephalic area). Whereas CCI induced microglial
      activation in both models, we observed a concomitant upregulation of IL-6 and
      ATF3 in the ipsilateral dorsal horn of the lumbar cord in SN-CCI rats but not in
      the ipsilateral spinal nucleus of the trigeminal nerve (Sp5c) in IoN-CCI rats.
      Preemptive treatment with minocycline (daily administration of 20 mg/kg, i.p.,
      for 2 weeks) partially prevented pain behavior and microglial activation in SN
      CCI rats but was ineffective in IoN-CCI rats. We show that IL-6 can upregulate OX
      42 and ATF3 expression in cultured microglia and neurons from spinal cord,
      respectively, as well as in the dorsal horn after acute intrathecal
      administration of the cytokine. We propose that IL-6 could be one of the
      promoters of the signaling cascade leading to abnormal pain behavior in SN-CCI
      but not IoN-CCI rats. Our data further support the idea that different
      pathophysiological mechanisms contribute to the development of cephalic versus
      extracephalic neuropathic pain.

PMID- 18716208
TI  - A molecular circuit composed of CPEB-1 and c-Jun controls growth hormone-mediated
      synaptic plasticity in the mouse hippocampus.
AB  - Cytoplasmic polyadenylation element binding protein 1 (CPEB-1) resides at
      postsynaptic sites in hippocampal neurons in which it controls polyadenylation
      induced translation. CPEB-1 knock-out (KO) mice display defects in some forms of
      synaptic plasticity and hippocampal-dependent memories. To identify CPEB-1
      regulated mRNAs, we used proteomics to compare polypeptides in wild-type (WT) and
      CPEB-1 KO hippocampus. Growth hormone (GH) was reduced in the KO hippocampus, as
      were the GH signaling molecules phospho-JAK2 and phospho-STAT3. GH mRNA and pre
      mRNA were reduced in the KO hippocampus, suggesting that CPEB-1 controls GH
      transcription. The transcription factor c-Jun, which binds the GH promoter, was
      also reduced in the KO hippocampus, as was its ability to coimmunoprecipitate
      chromatin containing the GH promoter. CPEB-1 binds c-Jun 3' untranslated region
      CPEs in vitro and coimmunoprecipitates c-Jun RNA in vivo. GH induces long-term
      potentiation (LTP) when applied to hippocampal slices from WT and CPEB-1 KO mice,
      but the magnitude of LTP induced by GH in KO mice is reduced. Pretreatment with
      GH did not reverse the LTP deficit observed in KO mice after theta-burst
      stimulation (TBS). Cordycepin, an inhibitor of polyadenylation, disrupted LTP
      induced by either GH application or TBS. Finally, GH application to hippocampal
      slices induced JAK2 phosphorylation in WT but not KO animals. These results
      indicate that CPEB-1 control of c-Jun mRNA translation regulates GH gene
      expression and resulting downstream signaling events (e.g., synaptic plasticity)
      in the mouse hippocampus.

PMID- 18716209
TI  - Motor neuron regeneration in adult zebrafish.
AB  - The mammalian spinal cord does not regenerate motor neurons that are lost as a
      result of injury or disease. Here we demonstrate that adult zebrafish, which show
      functional spinal cord regeneration, are capable of motor neuron regeneration.
      After a spinal lesion, the ventricular zone shows a widespread increase in
      proliferation, including slowly proliferating olig2-positive (olig2+) ependymo
      radial glial progenitor cells. Lineage tracing in olig2:green fluorescent protein
      transgenic fish indicates that these cells switch from a gliogenic phenotype to
      motor neuron production. Numbers of undifferentiated small HB9+ and islet-1+
      motor neurons, which are double labeled with the proliferation marker 5-bromo-2
      deoxyuridine (BrdU), are transiently strongly increased in the lesioned spinal
      cord. Large differentiated motor neurons, which are lost after a lesion, reappear
      at 6-8 weeks after lesion, and we detected ChAT+/BrdU+ motor neurons that were
      covered by contacts immunopositive for the synaptic marker SV2. These
      observations suggest that, after a lesion, plasticity of olig2+ progenitor cells
      may allow them to generate motor neurons, some of which exhibit markers for
      terminal differentiation and integration into the existing adult spinal
      circuitry.

PMID- 18716210
TI  - Regulator of G-protein signaling 10 promotes dopaminergic neuron survival via
      regulation of the microglial inflammatory response.
AB  - Epidemiological studies suggest that chronic use of nonsteroidal anti
      inflammatory drugs lowers the incidence of Parkinson's disease (PD) in humans and
      implicate neuroinflammatory processes in the death of dopamine (DA) neurons.
      Here, we demonstrate that regulator of G-protein signaling 10 (RGS10), a
      microglia-enriched GAP (GTPase accelerating protein) for Galpha subunits, is an
      important regulator of microglia activation. Flow-cytometric and
      immunohistochemical analyses indicated that RGS10-deficient mice displayed
      increased microglial burden in the CNS, and exposure to chronic systemic
      inflammation induced nigral DA neuron loss measured by unbiased stereology.
      Primary microglia isolated from brains of RGS10-deficient mice displayed
      dysregulated inflammation-related gene expression profiles under basal and
      stimulated conditions in vitro compared with that of primary microglia isolated
      from wild-type littermates. Similarly, knockdown of RGS10 in the BV2 microglia
      cell line resulted in dysregulated inflammation-related gene expression,
      overproduction of tumor necrosis factor (TNF), and enhanced neurotoxic effects of
      BV2 microglia on the MN9D dopaminergic cell line that could be blocked by
      addition of the TNF decoy receptor etanercept. Importantly, ablation of RGS10 in
      MN9D dopaminergic cells further enhanced their vulnerability to microglial
      derived death-inducing inflammatory mediators, suggesting a role for RGS10 in
      modulating the sensitivity of dopaminergic neurons against inflammation-mediated
      cell death. Together, our findings indicate that RGS10 limits microglial-derived
      TNF secretion and regulates the functional outcome of inflammatory stimuli in the
      ventral midbrain. RGS10 emerges as a novel drug target for prevention of
      nigrostriatal pathway degeneration, the neuropathological hallmark of PD.

PMID- 18716211
TI  - Dynamic regulation of the Kv2.1 voltage-gated potassium channel during brain
      ischemia through neuroglial interaction.
AB  - The physiological significance of neuroglial interactions in the CNS has been
      emphasized in neurological conditions such as epilepsy and brain ischemia. The
      Kv2.1 voltage-gated potassium channel is unique in its ability to form large
      clusters in the plasma membrane of neuronal cell bodies. We have previously shown
      that brain ischemia causes rapid dephosphorylation of Kv2.1 subunits and
      resultant activation of the ion channel function. However, the physiological
      significance of the channel clustering is unknown. Here we present evidence that
      clustered Kv2.1 channels in the neuronal plasma membrane are juxtaposed to
      axosomatic synapses and associated with astrocytic processes expressing high
      levels of glutamate transporters. In acute cortical slices, ischemic stress
      rapidly resulted in the dephosphorylation and dispersion of Kv2.1. Selective
      inhibition of metabolism in astrocytes was sufficient to induce Kv2.1
      dephosphorylation in neurons. Interestingly, these effects were blocked by the
      antagonists of ionotropic glutamate receptors, indicating the involvement of
      glutamate as the signal mediator between astrocytes and neurons. Furthermore, the
      pharmacological inhibition of glial glutamate transporter GLT-1 induced the
      similar Kv2.1 dephosphorylation, whereas exogenous glutamate alone was not
      efficacious. These results suggest that ischemic stress rapidly causes the
      dysfunction of glutamate transporters in astrocytes and resultant accumulation of
      glutamate in the extracellular space. The elevated glutamate may subsequently
      activate ionotropic glutamate receptors and result in the dephosphorylation of
      Kv2.1 in neurons. These findings implicate that Kv2.1 clusters are strategically
      situated at neuroglial junctions to achieve the rapid modulation after ischemic
      stress via glutamate signaling.

PMID- 18716212
TI  - Scenes unseen: the parahippocampal cortex intrinsically subserves contextual
      associations, not scenes or places per se.
AB  - The parahippocampal cortex (PHC) has been implicated in both place/scene
      processing and episodic memory. We proposed that this region should instead be
      seen as intrinsically mediating contextual associations and not place/scene
      processing or episodic memory exclusively. Given that place/scene processing and
      episodic memory both rely on associations, this modified framework provides a
      platform for reconciling what seemed like different roles assigned to the same
      region. Comparing scenes with scenes, we show here that the PHC responds
      significantly more strongly to scenes with rich contextual associations compared
      with scenes of equal visual qualities but less associations. This result adds
      unequivocal support to the view that the PHC mediates contextual associations in
      general rather than places or scenes proper, and necessitates a revision of the
      current view that the PHC contains a dedicated place/scenes "module."

PMID- 18716213
TI  - Mtap2 is a constituent of the protein network that regulates twik-related K+
      channel expression and trafficking.
AB  - Twik-related K+ (TREK) channels produce background currents that regulate cell
      excitability. In vivo, TREK-1 is involved in neuronal processes including
      neuroprotection against ischemia, general anesthesia, pain perception, and mood.
      Recently, we demonstrated that A-kinase anchoring protein AKAP150 binds to a
      major regulatory domain of TREK-1, promoting drastic changes in channel
      regulation by polyunsaturated fatty acids, pH, and stretch, and by G-protein
      coupled receptors to neurotransmitters and hormones. Here, we show that the
      microtubule-associated protein Mtap2 is another constituent of native TREK
      channels in the brain. Mtap2 binding to TREK-1 and TREK-2 does not affect
      directly channel properties but enhances channel surface expression and current
      density. This effect relies on Mtap2 binding to microtubules. Mtap2 and AKAP150
      interacting sites in TREK-1 are distinct and both proteins can dock
      simultaneously. Their effects on TREK-1 surface expression and activation are
      cumulative. In neurons, the three proteins are simultaneously detected in
      postsynaptic dense bodies. AKAP150 and Mtap2 put TREK channels at the center of a
      complex protein network that finely tunes channel trafficking, addressing, and
      regulation.

PMID- 18716214
TI  - The relationship between subthreshold and suprathreshold ocular dominance in cat
      primary visual cortex.
AB  - Primary visual cortex (V1) is the site at which right and left eye pathways are
      first integrated, leading to a representation of the visual world in depth. The
      ocular dominance (OD) of individual cortical neurons varies and may be changed by
      altering visual experience during the developmental critical period. Estimates of
      OD, commonly used to quantify the right and left eye synaptic inputs, have
      previously been based on spike rate. Membrane potential (V(m)), however, is more
      closely related to the synaptic inputs onto neurons and should therefore more
      closely reflect the degree of input from the two eyes. To determine the
      relationship between OD based on membrane potential and on spike rate,
      intracellular recordings were made from visual cortical neurons. OD based on
      spike rate was systematically more monocular than OD based on membrane potential.
      The discrepancy between membrane-potential OD and spike-rate OD may be accounted
      for by a simple model of V(m)-to-spike-rate transformation.

PMID- 18716215
TI  - Endogenous homer proteins regulate metabotropic glutamate receptor signaling in
      neurons.
AB  - Group I metabotropic glutamate receptors (mGluR1 and mGluR5) are important
      neuronal mediators of postsynaptic signaling that influence synaptic strength,
      plasticity, and other factors. Regulation of group I mGluR localization and
      function by Homer proteins appears to be a viable means for neurons to fine-tune
      these processes. The presence of different Homer isoforms can act as a switch to
      reprioritize mGluR1 and mGluR5 signaling at the point of IP(3) receptor
      activation by promoting or reducing activation of specific downstream effectors.
      Furthermore, these Homer-dependent effects on mGluR signaling may mechanistically
      underlie many of the long-term changes in neuronal function associated with
      changes in Homer protein expression described in the recent literature. However,
      most studies focusing on mGluR regulation by Homer proteins used relatively long
      term overexpression. Thus, a definitive demonstration of mGluR1/5 signal
      regulation by natively expressed Homer proteins has been elusive. I examined the
      ability of endogenous Homer 1a to alter mGluR signaling in rat sympathetic
      neurons and hippocampal autapses using pituitary adenylate cyclase activating
      peptide (PACAP) to induce native Homer 1a expression. In sympathetic neurons,
      both Homer 1a overexpression and PACAP treatment reversed the decrease in mGluR1
      mediated calcium current modulation associated with Homer 2b expression. In
      hippocampal autapses, PACAP treatment uncoupled postsynaptic mGluR5 from EPSC
      inhibition, similar to the effect of Homer 1a overexpression. In both cases, RNA
      silencing of Homer 1a but not control RNA interference treatment prevented the
      PACAP effect, suggesting that it resulted specifically from native Homer 1a
      expression.

PMID- 18716216
TI  - cGMP produced by NO-sensitive guanylyl cyclase essentially contributes to
      inflammatory and neuropathic pain by using targets different from cGMP-dependent
      protein kinase I.
AB  - A large body of evidence indicates that the release of nitric oxide (NO) is
      crucial for the central sensitization of pain pathways during both inflammatory
      and neuropathic pain. Here, we investigated the distribution of NO-sensitive
      guanylyl cyclase (NO-GC) in the spinal cord and in dorsal root ganglia, and we
      characterized the nociceptive behavior of mice deficient in NO-GC (GC-KO mice).
      We show that NO-GC is distinctly expressed in neurons of the mouse dorsal horn,
      whereas its distribution in dorsal root ganglia is restricted to non-neuronal
      cells. GC-KO mice exhibited a considerably reduced nociceptive behavior in models
      of inflammatory or neuropathic pain, but their responses to acute pain were not
      impaired. Moreover, GC-KO mice failed to develop pain sensitization induced by
      intrathecal administration of drugs releasing NO or carbon monoxide.
      Surprisingly, during spinal nociceptive processing, cGMP produced by NO-GC may
      activate signaling pathways different from cGMP-dependent protein kinase I
      (cGKI), whereas cGKI can be activated by natriuretic peptide receptor-B dependent
      cGMP production. Together, our results provide evidence that NO-GC is crucially
      involved in the central sensitization of pain pathways during inflammatory and
      neuropathic pain.

PMID- 18716217
TI  - The persistent sodium current generates pacemaker activities in the central
      pattern generator for locomotion and regulates the locomotor rhythm.
AB  - Rhythm generation in neuronal networks relies on synaptic interactions and
      pacemaker properties. Little is known about the contribution of the latter
      mechanisms to the integrated network activity underlying locomotion in mammals.
      We tested the hypothesis that the persistent sodium current (I(NaP)) is critical
      in generating locomotion in neonatal rodents using both slice and isolated spinal
      cord preparations. After removing extracellular calcium, 75% of interneurons in
      the area of the central pattern generator (CPG) for locomotion exhibited bursting
      properties and I(NaP) was concomitantly upregulated. Putative CPG interneurons
      such as commissural and Hb9 interneurons also expressed I(NaP)-dependent
      (riluzole-sensitive) bursting properties. Most bursting cells exhibited a
      pacemaker-like behavior (i.e., burst frequency increased with depolarizing
      currents). Veratridine upregulated I(NaP), induced riluzole-sensitive bursting
      properties, and slowed down the locomotor rhythm. This study provides evidence
      that I(NaP) generates pacemaker activities in CPG interneurons and contributes to
      the regulation of the locomotor activity.

PMID- 18716218
TI  - Population coding of reward magnitude in the orbitofrontal cortex of the rat.
AB  - Although single-cell coding of reward-related information in the orbitofrontal
      cortex (OFC) has been characterized to some extent, much less is known about the
      coding properties of orbitofrontal ensembles. We examined population coding of
      reward magnitude by performing ensemble recordings in rat OFC while animals
      learned an olfactory discrimination task in which various reinforcers were
      associated with predictive odor stimuli. Ensemble activity was found to represent
      information about reward magnitude during several trial phases, namely when
      animals moved to the reward site, anticipated reward during an immobile period,
      and received it. During the anticipation phase, Bayesian and template-matching
      reconstruction algorithms decoded reward size correctly from the population
      activity significantly above chance level (highest value of 43 and 48%,
      respectively; chance level, 33.3%), whereas decoding performance for the reward
      delivery phase was 76 and 79%, respectively. In the anticipation phase, the
      decoding score was only weakly dependent on the size of the neuronal group
      participating in reconstruction, consistent with a redundant, distributed
      representation of reward information. In contrast, decoding was specific for
      temporal segments within the structure of a trial. Decoding performance steeply
      increased across the first few trials for every rewarded odor, an effect that
      could not be explained by a nonspecific drift in response strength across trials.
      Finally, when population responses to a negative reinforcer (quinine) were
      compared with sucrose reinforcement, coding in the delivery phase appeared to be
      related to reward quality, and thus was not based on ingested liquid volume.

PMID- 18716219
TI  - Knock-in mice lacking the PDZ-ligand motif of mGluR7a show impaired PKC-dependent
      autoinhibition of glutamate release, spatial working memory deficits, and
      increased susceptibility to pentylenetetrazol.
AB  - The metabotropic glutamate receptor 7 (mGluR7) is widely expressed throughout the
      brain and primarily localized at presynaptic active zones, where it is thought to
      regulate neurotransmitter release. Protein interacting with C kinase 1 (PICK1), a
      postsynaptic density protein-95/disc-large tumor suppressor protein/zonula
      occludens-1 (PDZ)-domain protein, binds to the three C-terminal amino acids (
      LVI) of the predominant mGluR7 splice variant, mGluR7a, and has been implicated
      in the synaptic clustering of this receptor. Here, we generated knock-in mice in
      which the C-terminal LVI coding sequence of exon 10 of the mGluR7 gene was
      replaced by three alanine codons (-AAA). Immunoprecipitation showed that the
      PICK1-mGluR7a interaction is disrupted in mGluR7a(AAA/AAA) mice. However, the
      synaptic localization of mGluR7a was not altered in cultured hippocampal neurons
      and brain sections prepared from the knock-in animals. In cerebellar granule cell
      cultures, the group III mGluR agonist l-AP-4 decreased the frequency of
      spontaneous excitatory currents in neurons derived from wild-type but not
      mGluR7a(AAA/AAA) mice, consistent with the interaction between mGluR7a and PICK1
      being required for protein kinase C-mediated inhibition of glutamate release. At
      the behavioral level, the mGluR7a(AAA/AAA) mice showed no deficits in motor
      coordination, pain sensitivity, and anxiety but exhibited significant defects in
      hippocampus-dependent spatial working memory. In addition, they displayed a high
      susceptibility to the convulsant drug pentylenetetrazole. Together, these results
      indicate that PICK1 binding to the C-terminal region of mGluR7a is crucial for
      agonist-triggered presynaptic signaling in vivo.

PMID- 18716220
TI  - A mechanism distinct from highwire for the Drosophila ubiquitin conjugase
      bendless in synaptic growth and maturation.
AB  - The signaling mechanisms that allow the conversion of a growth cone into a mature
      and stable synapse are yet to be completely understood. Ubiquitination plays key
      regulatory roles in synaptic development and may be involved in this process.
      Previous studies identified the Drosophila ubiquitin conjugase bendless (ben) to
      be important for central synapse formation, but the precise role it plays has not
      been elucidated. Our studies indicate that Ben plays a pivotal role in synaptic
      growth and maturation. We have determined that an incipient synapse is present
      with a high penetrance in ben mutants, suggesting that Ben is required for a
      developmental step after target recognition. We used cell-autonomous rescue
      experiments to show that Ben has a presynaptic role in synapse growth. We then
      harnessed the TARGET system to transiently express UAS (upstream activating
      sequence)-ben in a ben mutant background and identified a well defined critical
      period for Ben function in establishing a full-grown, mature synaptic terminal.
      We demonstrate that the protein must be present at a time point before but not
      during the actual growth process. We also provide phenotypic evidence
      demonstrating that Ben is not a part of the signal transduction pathway involving
      the well characterized ubiquitin ligase highwire. We conclude that Bendless
      functions as a novel developmental switch that permits the transition from axonal
      growth and incipient synapse formation to synaptic growth and maturation in the
      CNS.

PMID- 18716221
TI  - Reverse of age-dependent memory impairment and mitochondrial DNA damage in
      microglia by an overexpression of human mitochondrial transcription factor a in
      mice.
AB  - Mitochondrial DNA (mtDNA) is highly susceptible to injury induced by reactive
      oxygen species (ROS). During aging, mutations of mtDNA accumulate to induce
      dysfunction of the respiratory chain, resulting in the enhanced ROS production.
      Therefore, age-dependent memory impairment may result from oxidative stress
      derived from the respiratory chain. Mitochondrial transcription factor A (TFAM)
      is now known to have roles not only in the replication of mtDNA but also its
      maintenance. We herein report that an overexpression of TFAM in HeLa cells
      significantly inhibited rotenone-induced mitochondrial ROS generation and the
      subsequent NF-kappaB (nuclear factor-kappaB) nuclear translocation. Furthermore,
      TFAM transgenic (TG) mice exhibited a prominent amelioration of an age-dependent
      accumulation of lipid peroxidation products and a decline in the activities of
      complexes I and IV in the brain. In the aged TG mice, deficits of the motor
      learning memory, the working memory, and the hippocampal long-term potentiation
      (LTP) were also significantly improved. The expression level of interleukin-1beta
      (IL-1beta) and mtDNA damages, which were predominantly found in microglia,
      significantly decreased in the aged TG mice. The IL-1beta amount markedly
      increased in the brain of the TG mice after treatment with lipopolysaccharide
      (LPS), whereas its mean amount was significantly lower than that of the LPS
      treated aged wild-type mice. At the same time, an increased mtDNA damage in
      microglia and an impaired hippocampal LTP were also observed in the LPS-treated
      aged TG mice. Together, an overexpression of TFAM is therefore considered to
      ameliorate age-dependent impairment of the brain functions through the prevention
      of oxidative stress and mitochondrial dysfunctions in microglia.

PMID- 18716222
TI  - Downregulation of dendritic I(h) in CA1 pyramidal neurons after LTP.
AB  - Hyperpolarization-activated (h)-channels occupy a central position in dendritic
      function. Although it has been demonstrated that these channels are upregulated
      after large depolarizations to reduce dendritic excitation, it is not clear
      whether they also support other forms of long-term plasticity. We show here that
      nearly maximal long-term potentiation (LTP) induced by theta-burst pairing
      produced upregulation in h-channel activity in CA1 pyramidal neurons. In
      contrast, moderate LTP induced by spike-timing-dependent plasticity or high
      frequency stimulation (HFS) downregulated the h-current (I(h)) in the dendrites.
      After HFS-induced LTP, the h-conductance (G(h)) was reduced without changing its
      activation. Pharmacological blockade of I(h) had no effect on LTP induction, but
      occluded EPSP-to-spike potentiation, an input-specific facilitation of dendritic
      integration. Dynamic-clamp reduction of G(h) locally in the dendrite mimicked the
      effects of HFS and enhanced synaptic integration in an input-selective way. We
      conclude that dendritic I(h) is locally downregulated after induction of
      nonmaximal LTP, thus facilitating integration of the potentiated input.

PMID- 18716223
TI  - Wnt regulates axon behavior through changes in microtubule growth directionality:
      a new role for adenomatous polyposis coli.
AB  - Axon guidance and target-derived signals control axonal behavior by regulating
      the cytoskeleton through poorly defined mechanisms. In particular, how these
      signaling molecules regulate the growth and directionality of microtubules is not
      well understood. Here we examine the effect of Wnts on growth cone remodeling, a
      process that precedes synapse formation. Time-lapse recordings reveal that Wnt3a
      rapidly inhibits growth cone translocation while inducing growth cone
      enlargement. These changes in axonal behavior are associated with changes in the
      organization of microtubules. Time-lapse imaging of EB3-GFP (green fluorescent
      protein)-labeled microtubule plus-ends demonstrates that Wnt3a regulates
      microtubule directionality, resulting in microtubule looping, growth cone
      pausing, and remodeling. Analyses of Dishevelled-1 (Dvl1) mutant neurons
      demonstrate that Dvl1 is required for Wnt-mediated microtubule reorganization and
      axon remodeling. Wnt signaling directly affects the microtubule cytoskeleton by
      unexpectedly inducing adenomatous polyposis coli (APC) loss from microtubule plus
      ends. Consistently, short hairpin RNA knockdown of APC mimics Wnt3a function.
      Together, our findings define APC as a key Wnt signaling target in the regulation
      of microtubule growth direction.

PMID- 18716224
TI  - Comparison of two PCR-based human papillomavirus genotyping methods.
AB  - We compared two consensus primer PCR human papillomavirus (HPV) genotyping
      methods for the detection of individual HPV genotypes and carcinogenic HPV
      genotypes as a group, using a stratified sample of enrollment cervical specimens
      from sexually active women participating in the NCI/Costa Rica HPV16/18 Vaccine
      Efficacy Trial. For the SPF(10) method, DNA was extracted from 0.1% of the
      cervical specimen by using a MagNA Pure LC instrument, a 65-bp region of the HPV
      L1 gene was targeted for PCR amplification by using SPF(10) primers, and 25
      genotypes were detected by reverse-line blot hybridization of the amplicons. For
      the Linear Array (LA) method, DNA was extracted from 0.5% of the cervical
      specimen by using an MDx robot, a 450-bp region of the HPV L1 gene was targeted
      for PCR amplification by using PGMY09/11 L1 primers, and 37 genotypes were
      detected by reverse-line blot hybridization of the amplicons. Specimens (n =
      1,427) for testing by the LA method were randomly selected from strata defined on
      the basis of enrollment test results from the SPF(10) method, cytology, and
      Hybrid Capture 2. LA results were extrapolated to the trial cohort (n = 5,659).
      The LA and SPF(10) methods detected 21 genotypes in common; HPV16, -18, -31, -33,
      -35, -39, -45, -51, -52, -56, -58, -59, -66, -68, and -73 were considered the
      carcinogenic HPV genotypes. There was no difference in the overall results for
      grouped detection of carcinogenic HPV by the SPF(10) and LA methods (35.3% versus
      35.9%, respectively; P = 0.5), with a 91.8% overall agreement and a kappa value
      of 0.82. In comparisons of individual HPV genotypes, the LA method detected
      significantly more HPV16, HPV18, HPV39, HPV58, HPV59, HPV66, and HPV68/73 and
      less HPV31 and HPV52 than the SPF(10) method; inclusion of genotype-specific
      testing for HPV16 and HPV18 for those specimens testing positive for HPV by the
      SPF(10) method but for which no individual HPV genotype was detected abrogated
      any differences between the LA and SPF(10) methods. The LA method detected more
      carcinogenic-HPV-genotype infections per specimen than the SPF(10) method (P <
      0.001). In conclusion, the LA method and the SPF(10) method with HPV16 and HPV18
      genotype-specific detection among ungenotyped HPV-positive specimens were
      comparable for detection of HPV16 and HPV18, the two HPV genotypes targeted by
      current prophylactic HPV vaccines. Both approaches are suitable for monitoring
      the impact of HPV16/18 vaccines in clinical trials.

PMID- 18716225
TI  - Evaluation of a multiplex PCR assay (Bruce-ladder) for molecular typing of all
      Brucella species, including the vaccine strains.
AB  - An evaluation of a multiplex PCR assay (Bruce-ladder) was performed in seven
      laboratories using 625 Brucella strains from different animal and geographical
      origins. This robust test can differentiate in a single step all of the classical
      Brucella species, including those found in marine mammals and the S19, RB51, and
      Rev.1 vaccine strains.

PMID- 18716226
TI  - Validation of cultivation and PCR methods for diagnosis of Lyme neuroborreliosis.
AB  - Borrelial infection may manifest with a wide range of clinical signs, and in many
      cases, microbiological findings are essential for a proper diagnosis. This study
      included 48 patients with a working clinical diagnosis of Lyme neuroborreliosis,
      45 patients with a working clinical diagnosis of suspected Lyme neuroborreliosis,
      and a control group comprising 42 patients with tick-borne encephalitis and 21
      neurosurgical patients. The aim of the study was to analyze and compare findings
      of two PCR methods and Borrelia burgdorferi sensu lato culture results by
      examination of prospectively collected cerebrospinal fluid (CSF) and blood
      specimens from patients with clinical features of Lyme neuroborreliosis.
      Borrelial DNA was detected with at least one of the PCR approaches in 16/135
      (11.9%) blood samples and 24/156 (15.4%) CSF samples. Using MseI restriction of
      PCR products of the amplified rrf-rrl region, we identified the majority of
      strains as Borrelia afzelii. Borreliae were isolated from 1/135 (0.7%) blood
      samples and from 5/156 (3.2%) CSF specimens. Using MluI restriction for
      characterization of isolated strains, Borrelia garinii was identified in all CSF
      isolates. Our study revealed that different approaches for direct demonstration
      of borrelial infection give distinct results, that there is an urgent need for
      standardization of the methods for direct detection of borrelial infection, and
      that the design of studies evaluating the validation of such methods should
      include appropriate control group(s) to enable assessment of both sensitivity and
      specificity.

PMID- 18716227
TI  - Biological and phylogenetic characterization of pigeon paramyxovirus serotype 1
      circulating in wild North American pigeons and doves.
AB  - As part of West Nile virus surveillance programs in Rhode Island and eastern
      Texas between 2000 and 2007, brain tissue was collected from 5,608 dead birds
      representing 21 avian orders found in public places or reported by homeowners.
      Fifteen Newcastle disease virus isolates were recovered only from birds of the
      order Columbiformes and were positively identified by the USDA-validated real
      time reverse transcription-PCR assay targeting the matrix gene and more
      specifically as pigeon paramyxovirus serotype 1 (PPMV-1) by hemagglutinin
      inhibition with monoclonal antibodies. Based upon partial genomic sequencing and
      phylogenetic analysis, the newly isolated viruses represent a distinct sublineage
      within class II genotype VIb. All of the viruses (15/15) were classified as
      virulent based upon their fusion cleavage site motif ((112)RRKKRF(117)) and
      intracerebral pathogenicity indices of >0.7 (ranging from 0.98 to 1.35); however,
      these viruses escaped detection by the fusion gene-based real-time PCR test for
      virulence. Modifications introduced to the probe site of the fusion gene-based
      assay allowed rapid virulence detection within this distinct sublineage.

PMID- 18716228
TI  - Helcococcus ovis, an emerging pathogen in bovine valvular endocarditis.
AB  - The initial isolation of Helcococcus ovis from a valvular thrombus prompted us to
      investigate the prevalence of this bacterium in bovine valvular endocarditis.
      Specimens from 55 affected hearts were examined by culture using Columbia blood
      agar and cross streaking the inoculated plate with a Staphylococcus aureus
      strain. As confirmed by 16S rRNA gene sequencing, H. ovis was isolated with an
      unexpectedly high frequency of 33%, predominantly as heavy growth and pure
      culture. The majority of H. ovis isolates showed distinct satellitism around S.
      aureus and pyridoxal dependency, resembling "nutritionally variant streptococci"
      (now assigned to the genera Abiotrophia and Granulicatella). Using the API rapid
      ID 32 Strep, API ZYM, and Rosco Diatabs systems, incongruent results were
      obtained for alkaline phosphatase, beta-galactosidase, beta-glucuronidase, and
      leucine aminopeptidase activities. Based on the satellitism/pyridoxal dependency;
      hemolysis on blood agar; the API rapid ID 32 Strep results for arginine
      dihydrolase, alpha-galactosidase, beta-galactosidase, beta-glucuronidase, and
      pyroglutamic acid arylamidase activities; hippurate hydrolysis; and acidification
      of sucrose, a scheme for the identification of H. ovis and its differentiation
      from other members of the Helcococcus genus and the pyridoxal-dependent species
      Abiotrophia defectiva, Granulicatella adiacens, and Granulicatella elegans is
      proposed. By establishing specific fluorescence in situ hybridization, large H.
      ovis aggregates were specifically detected within the fibrinous exudate of the
      valvular thrombi. Our results demonstrate for the first time that H. ovis
      represents an emerging pathogen in bovine valvular endocarditis that is
      frequently isolated if appropriate culture conditions are used.

PMID- 18716229
TI  - Effects of antibiotic treatment on the results of nested PCRs for scrub typhus.
AB  - In order to determine the effects of antibiotic treatment on the results of
      nested PCRs for scrub typhus, we investigated the frequency of positive outcomes
      at various times after antibiotic administration in patients with scrub typhus.
      The rate of detection by nested PCR with blood buffy coat before antibiotic
      administration was 90.5%. However, this decreased to 60.5% within 3 days after
      administration of antibiotics such as doxycycline and rifampin and to 10% by the
      fourth day following antibiotic administration. Since the sensitivity of nested
      PCR can be affected by antibiotic administration, clinicians should perform this
      PCR before antibiotic administration and at the latest within 3 days after
      antibiotic administration.

PMID- 18716230
TI  - Discordance between mycobacterial interspersed repetitive-unit-variable-number
      tandem-repeat typing and IS6110 restriction fragment length polymorphism
      genotyping for analysis of Mycobacterium tuberculosis Beijing strains in a
      setting of high incidence of tuberculosis.
AB  - IS6110 restriction fragment length polymorphism (RFLP) genotyping is the most
      widely used genotyping method to study the epidemiology of Mycobacterium
      tuberculosis. However, due to the complexity of the IS6110 RFLP genotyping
      technique, and the interpretation of RFLP data, mycobacterial interspersed
      repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) genotyping has been
      proposed as the new genotyping standard. This study aimed to determine the
      discriminatory power of different MIRU-VNTR locus combinations relative to IS6110
      RFLP genotyping, using a collection of Beijing genotype M. tuberculosis strains
      with a well-established phylogenetic history. Clustering, diversity index,
      clustering concordance, concordance among unique genotypes, and divergent and
      convergent evolution were calculated for seven combinations of 27 different MIRU
      VNTR loci and compared to IS6110 RFLP results. Our results confirmed previous
      findings that MIRU-VNTR genotyping can be used to estimate the extent of recent
      or ongoing transmission. However, molecular epidemiological linking of cases
      varied significantly depending on the genotyping method used. We conclude that
      IS6110 RFLP and MIRU-VNTR loci evolve independently and at different rates, which
      leads to discordance between transmission chains predicted by the respective
      genotyping methods. Concordance between the two genotyping methods could be
      improved by the inclusion of genetic distance (GD) into the clustering formulae
      for some of the MIRU-VNTR loci combinations. In summary, our findings differ from
      previous reports, which may be explained by the fact that in settings of low
      tuberculosis incidence, the genetic distance between epidemiologically unrelated
      isolates was sufficient to define a strain using either marker, whereas in
      settings of high incidence, continuous evolution and persistence of strains
      revealed the weaknesses inherent to these markers.

PMID- 18716231
TI  - Deployable laboratory response to emergence of melioidosis in central Sri Lanka.
AB  - A portable molecular diagnostic laboratory was used to provide molecular
      confirmation of suspected melioidosis cases seen at Peradeniya Hospital, central
      Sri Lanka. Soil supernatants from rice field and rubber plantation samples also
      produced PCR-positive results. These procedures could be used for melioidosis
      field work in other remote locations.

PMID- 18716232
TI  - Molecular characterization of equine rotavirus in Ireland.
AB  - Group A rotaviruses are important causative agents of severe, acute dehydrating
      diarrhea in foals. A total of 86 rotavirus-positive fecal samples, collected from
      diarrheic foals from 11 counties in three of the four provinces of Ireland, were
      obtained from the Irish Equine Centre in Kildare during a 7-year (1999 to 2005)
      passive surveillance study and were characterized molecularly to establish the
      VP7 (G type) and VP4 (P type) antigenic specificities. Fifty-eight samples
      (67.5%) were found to contain G3 viruses, while in 26 samples (30.2%) the
      rotaviruses were typed as G14 and in 2 samples (2.3%) there was a mixed
      infection, G3 plus G14. All samples except for two, which were untypeable, were
      characterized as P[12]. Fifty-eight percent of the samples were obtained from
      County Kildare, the center of the Irish horse industry, where an apparent shift
      from G3P[12] to G14P[12] was observed in 2003. By sequence analysis of the VP7
      protein, the G3 Irish strains were shown to resemble viruses of the G3A subtype
      (H2-like) (97.1 to 100% amino acid [aa] identity), while the G14 Irish strains
      displayed 93.9 to 97.1% aa identity to other G14 viruses. In the VP8* fragment of
      the VP4 protein, the P[12] Irish viruses displayed high conservation (92.3 to
      100% aa) with other equine P[12] viruses. Worldwide, G3P[12] and G14P[12] are the
      most prevalent equine rotavirus strains, and G3P[12] vaccines have been developed
      for prevention of rotavirus-associated diarrhea in foals. Investigations of the
      VP7/VP4 diversity of the circulating equine viruses and the dynamics of strain
      replacement are important for better assessing the efficacies of the vaccines.

PMID- 18716233
TI  - Two-year study evaluating the potential loss of methicillin resistance in a
      methicillin-resistant Staphylococcus aureus culture collection.
AB  - A reported loss of mecA prompted us to monitor 360 cryostocked methicillin
      resistant Staphylococcus aureus strains for stability. Concurrently, 14 well
      characterized strains were stored in a Microbank preservation system and
      subjected to multiple freeze-thaw events. There were no significant declines in
      the methicillin-resistant populations with either method over a two-year period.

PMID- 18716234
TI  - Acne is not associated with yet-uncultured bacteria.
AB  - Current clinical and microbiological information on acne fails to demonstrate a
      clear association between particular species, including Propionibacterium acnes,
      and disease, and the disease continues to be a considerable problem. To test if
      acne is associated with hitherto uncultured bacteria residing in diseased skin
      follicles, sequencing and phylogenetic analysis of approximately 5,700 amplified
      and cloned 16S rRNA genes were used to determine the microbial diversity in
      follicles from acne patients and healthy individuals and from the superficial
      skin of acne patients. Follicles from healthy skin were exclusively colonized by
      P. acnes, whereas the follicular microbiota of acne patients included, in
      addition, Staphylococcus epidermidis and minor proportions of other species. In
      comparison, samples from superficial skin showed a complex microbiota represented
      by 12 to 16 bacterial species. The findings of the study exclude the possibility
      that acne is associated with yet-uncultured bacteria and shows that healthy skin
      follicles constitute a remarkably exclusive habitat allowing colonization only by
      P. acnes.

PMID- 18716236
TI  - Practice parameter: the diagnostic evaluation and treatment of trigeminal
      neuralgia (an evidence-based review): report of the Quality Standards
      Subcommittee of the American Academy of Neurology and the European Federation of
      Neurological Societies.
AB  - BACKGROUND: Trigeminal neuralgia (TN) is a common cause of facial pain. PURPOSE:
      To answer the following questions: 1) In patients with TN, how often does routine
      neuroimaging (CT, MRI) identify a cause? 2) Which features identify patients at
      increased risk for symptomatic TN (STN; i.e., a structural cause such as a
      tumor)? 3) Does high-resolution MRI accurately identify patients with
      neurovascular compression? 4) Which drugs effectively treat classic and
      symptomatic trigeminal neuralgia? 5) When should surgery be offered? 6) Which
      surgical technique gives the longest pain-free period with the fewest
      complications and good quality of life? METHODS: Systematic review of the
      literature by a panel of experts. CONCLUSIONS: In patients with trigeminal
      neuralgia (TN), routine head imaging identifies structural causes in up to 15% of
      patients and may be considered useful (Level C). Trigeminal sensory deficits,
      bilateral involvement of the trigeminal nerve, and abnormal trigeminal reflexes
      are associated with an increased risk of symptomatic TN (STN) and should be
      considered useful in distinguishing STN from classic trigeminal neuralgia (Level
      B). There is insufficient evidence to support or refute the usefulness of MRI to
      identify neurovascular compression of the trigeminal nerve (Level U).
      Carbamazepine (Level A) or oxcarbazepine (Level B) should be offered for pain
      control while baclofen and lamotrigine (Level C) may be considered useful. For
      patients with TN refractory to medical therapy, Gasserian ganglion percutaneous
      techniques, gamma knife, and microvascular decompression may be considered (Level
      C). The role of surgery vs pharmacotherapy in the management of TN in patients
      with MS remains uncertain.

PMID- 18716235
TI  - Cobblestone-like brain dysgenesis and altered glycosylation in congenital cutis
      laxa, Debre type.
AB  - OBJECTIVE: To delineate a new syndrome of brain dysgenesis and cutis laxa based
      on the description of 11 patients belonging to nine unrelated families recruited
      through an international collaboration effort. METHODS: Careful clinical
      assessment of patients from birth to the age of 23 years with follow-up studies
      ranging from 3 to 20 years. Biochemical studies of serum proteins glycosylation
      by isoelectric focusing and capillary zone electrophoresis were performed in 10
      patients. Brain MRI studies using conventional methods were analyzed in eight
      patients. RESULTS: An expanded clinical spectrum of a syndrome comprising facial
      dysmorphia (enlarged anterior fontanelles, downward slant of palpebral fissures,
      prominent root of the nose), a connective tissue disorder (inguinal hernia, hip
      dislocation, high myopia), and neurologic impairment was defined. Early
      developmental delay was followed by onset of generalized seizures by the end of
      the first decade and a subsequent neurodegenerative course. A defect of N- or N-
      plus O-glycosylation of serum transferrins and ApoCIII was observed in 10
      patients. An unusual cobblestone-like cortical malformation over the frontal and
      parietal regions was seen in eight patients and cerebellar abnormalities,
      including two patients with Dandy-Walker malformation, were observed in three
      patients. CONCLUSIONS: Our results suggest that autosomal recessive cutis laxa,
      Debre type, initially considered a dermatologic syndrome, is a multisystemic
      disorder with cobblestone-like brain dysgenesis manifesting as developmental
      delay and an epileptic neurodegenerative syndrome. It might represent a metabolic
      cause of Dandy-Walker malformation. It is associated with a deficient N- and-O
      glycosylation of proteins and shares many similarities with muscle-eye-brain
      syndromes.

PMID- 18716237
TI  - Blink to visual threat does not herald consciousness in the vegetative state.

PMID- 18716282
TI  - Making bigger brains-the evolution of neural-progenitor-cell division.
AB  - Relative brain size differs markedly between species. This variation might
      ultimately result from differences in the cell biology of neural progenitors,
      which might underlie their different proliferative potential. On the basis of the
      cell-biological properties of neural progenitors of animals of varying brain size
      and complexity (namely, Drosophila melanogaster, rodents and primates), we
      hypothesize that the evolution of four related cell-biological features has
      contributed to increases in neuron number. Three of these features-the
      pseudostratification of the progenitor layer, the loss of (Inscuteable-mediated)
      mitotic-spindle rotation and the evolution of proteins (such as Aspm) that
      maintain the precision of symmetric progenitor division-affect the mode of cell
      division in the apically dividing progenitors of the ventricular zone. The fourth
      feature, however, concerns the evolution of the basally dividing progenitors of
      the subventricular zone. In rodents, these basal (or intermediate) progenitors
      lack cell polarity, whereas in primates a subpopulation of radial, presumably
      polarized, progenitors has evolved (outer-subventricular-zone progenitors). These
      cells undergo basal mitoses and are thought to retain epithelial characteristics.
      We propose the epithelial-progenitor hypothesis, which argues that evolutionary
      changes that promote the maintenance of epithelial features in neural
      progenitors, including outer-subventricular-zone progenitors, have been
      instrumental in the expansion of the cerebral cortex in primates.

PMID- 18716283
TI  - Rac regulates the interaction of fascin with protein kinase C in cell migration.
AB  - Fascin is an actin-bundling protein that is low or absent in normal epithelia;
      its upregulation correlates with poor prognosis in many human carcinomas. We have
      recently demonstrated in mouse xenograft models that fascin contributes to tumour
      development and metastasis through its dual actin-bundling and active PKC-binding
      activities. Rac was implicated as a regulator of fascin-dependent colon carcinoma
      cell migration in vitro. Here, we tested the hypothesis that Rac regulates the
      interaction of fascin with active PKC. The major conventional PKC in colon
      carcinoma cells is protein kinase Cgamma (PKCgamma). Endogenous PKCgamma, fascin
      and Rac1 colocalised at lamellipodial margins of migrating cells. Colocalisation
      of fascin and PKCgamma depended on Rac activity, and inhibition of Rac decreased
      PKCgamma activity in cell extracts but not in vitro. Fluorescence resonance
      energy transfer/fluorescence lifetime imaging microscopy uncovered that fascin
      and PKCgamma interact in protrusions and filopodia of migrating cells.
      Mechanistically, the interaction depended on phosphorylated fascin, active
      PKCgamma and active Rac, but not on active Cdc42. The activity of Rac on the
      fascin/PKC complex was mediated in part by Pak. Elucidation of this novel pathway
      for regulation of the fascin/PKCgamma complex in migrating carcinoma cells
      suggests novel targets for therapeutic intervention in metastasis.

PMID- 18716284
TI  - Accelerated re-epithelialization in Dpr2-deficient mice is associated with
      enhanced response to TGFbeta signaling.
AB  - Members of the Dapper (Dpr)/Dact protein family are involved in the regulation of
      distinct signaling pathways, including TGFbeta/Nodal, canonical and noncanonical
      Wnt pathways. Three Dpr genes, Dpr1, Dpr2 and Dpr3, are expressed in mouse
      embryos and in many adult tissues; however, their in vivo functions have not been
      reported. In this study, we generated Dpr2-deficient mice using a gene-knockout
      approach. Homozygous Dpr2 knockout (Dpr2(-/-)) embryos developed normally and
      postnatal Dpr2(-/-) mice grew to adulthood without obvious morphological or
      behavioral defects. We found that Dpr2 was expressed highly in epidermal
      keratinocytes and in hair follicles of adult mice, and that Dpr2 deficiency
      resulted in accelerated re-epithelialization during cutaneous wound healing.
      Furthermore, we demonstrated that loss of Dpr2 function enhanced the responses of
      keratinocytes to TGFbeta stimulation, and that TGFbeta signals promoted adhesion
      to fibronectin and migration of keratinocytes, by regulating the expression of
      specific integrin genes. Thus, Dpr2 plays an inhibitory role in the re
      epithelialization of adult skin wounds by attenuating TGFbeta signaling.

PMID- 18716285
TI  - Mitochondrial shuttling of CAP1 promotes actin- and cofilin-dependent apoptosis.
AB  - Mitochondria play a central role in regulating apoptosis by releasing
      proapoptotic contents such as cytochrome c, and generating reactive oxygen
      species (ROS). Early in apoptosis, proteins translocate to mitochondria to
      promote the release of their contents. Here, we show that the actin- and cofilin
      interacting protein CAP1 has a role in apoptosis. When we induced apoptosis, CAP1
      rapidly translocated to the mitochondria independently of caspase activation.
      Translocation was proapoptotic because CAP1-knockdown cells were resistant to
      apoptosis inducers. Overexpression of wild-type CAP1 did not stimulate apoptosis
      on its own, but stimulated cofilin-induced apoptosis. Apoptosis induction
      required a mitochondrial-targeting domain, localized in the N-terminus and also
      the actin-binding domain in the C-terminus. Taken together, these studies suggest
      that CAP1 provides a direct link from the actin cytoskeleton to the mitochondria
      by functioning as an actin shuttle.

PMID- 18716286
TI  - Regulation of intracellular signaling cascades by GNRH pulse frequency in the rat
      pituitary: roles for CaMK II, ERK, and JNK activation.
AB  - Pulsatile GnRH (GNRH) differentially regulates LH and FSH subunit genes, with
      faster frequencies favoring Lhb transcription and slower favoring Fshb. Various
      intracellular pathways mediate the effects of GNRH, including CaMK II (CAMK2),
      ERK, and JNK. We examined whether activation of these pathways is regulated by
      GNRH pulse frequency in vivo. GNRH-deficient rats received GNRH pulses (25 ng
      i.v. every 30 or 240 min for 8 h, vehicle to controls). Pituitaries were
      collected 5 min after the last pulse, bisected, and one half processed for RNA
      (to measure beta subunit primary transcripts [PTs]) and the other for protein.
      Phosphorylated CAMK2 (phospho-CAMK2), ERK (mitogen-activated protein kinase 1/3
      [MAPK1/3], also known as p42 ERK2 and p44 ERK1, respectively), and JNK (MAPK8/9,
      also known as p46 JNK1 and p54 JNK2, respectively) were determined by Western
      blotting. The 30-min pulses maximally stimulated Lhb PT (8-fold), whereas 240 min
      was optimal for Fshb PT (3-fold increase). Both GNRH pulse frequencies increased
      phospho-CAMK2 4-fold. Activation of MAPK1/3 was stimulated by both 30- and 240
      min pulses, but phosphorylation of MAPK3 was significantly greater following
      slower GNRH pulses (240 min: 4-fold, 30 min: 2-fold). MAPK8/9 activation was
      unchanged by pulsatile GNRH in this paradigm, but as previous results showed that
      GNRH-induced activation of MAPK8/9 is delayed, 5 min after GNRH may not be
      optimal to observe MAPK8/9 activation. These data show that CAMK2 is activated by
      GNRH, but not in a frequency-dependant manner, whereas MAPK3 is maximally
      stimulated by slow-frequency GNRH pulses. Thus, the ERK response to slow pulse
      frequency is part of the mechanisms mediating Fhb transcriptional responses to
      GNRH.

PMID- 18716287
TI  - Molecular cloning and expression of the CRISP family of proteins in the boar.
AB  - The family of mammalian cysteine-rich secretory proteins (CRISP) have been well
      characterized in the rat, mouse, and human. Here we report the molecular cloning
      and expression analysis of CRISP1, CRISP2, and CRISP3 in the boar. A partial
      sequence published in the National Center for Biotechnology Information (NCBI)
      database was used to derive the full-length sequences for CRISP1 and CRISP2 using
      rapid amplification of cDNA ends. RT-PCR confirmed the expression of these mRNAs
      in the boar reproductive tract, and real time RT-PCR showed CRISP1 to be highly
      expressed throughout the epididymis, with CRISP2 highly expressed in the testis.
      A search of the porcine genomic sequence in the NCBI database identified a BAC
      (CH242-199E6) encoding the CRISP1 gene. This BAC is derived from porcine
      Chromosome 7 and is syntenic with the regions of the mouse, rat, and human
      genomes encoding the CRISP gene family. This BAC was found to encode a third
      CRISP protein with a predicted amino acid sequence of high similarity to human
      CRISP3. Using RT-PCR we show that CRISP3 expression in the boar reproductive
      tract is confined to the prostate. Recombinant porcine (rp) CRISP2 protein was
      produced and purified. When incubated with capacitated boar sperm, rpCRISP2
      induced an acrosome reaction, consistent with its demonstrated ability to alter
      the activity of calcium channels.

PMID- 18716288
TI  - Hormonal regulation of MicroRNA expression in periovulatory mouse mural granulosa
      cells.
AB  - MicroRNAs (miRNAs) mediate posttranscriptional gene regulation by binding to the
      3' untranslated region of messenger RNAs to either inhibit or enhance
      translation. The extent and hormonal regulation of miRNA expression by ovarian
      granulosa cells and their role in ovulation and luteinization is unknown. In the
      present study, miRNA array analysis was used to identify 212 mature miRNAs as
      expressed and 13 as differentially expressed in periovulatory granulosa cells
      collected before and after an ovulatory dose of hCG. Two miRNAs, Mirn132 and
      Mirn212 (also known as miR-132 and miR-212), were found to be highly upregulated
      following LH/hCG induction and were further analyzed. In vivo and in vitro
      temporal expression analysis by quantitative RT-PCR confirmed that LH/hCG and
      cAMP, respectively, increased transcription of the precursor transcript as well
      as the mature miRNAs. Locked nucleic acid oligonucleotides complementary to
      Mirn132 and Mirn212 were shown to block cAMP-mediated mature miRNA expression and
      function. Computational analyses indicated that 77 putative mRNA targets of
      Mirn132 and Mirn212 were expressed in ovarian granulosa cells. Furthermore, upon
      knockdown of Mirn132 and Mirn212, a known target of Mirn132, C-terminal binding
      protein 1, showed decreased protein levels but no change in mRNA levels. The
      following studies are the first to describe the extent of miRNA expression within
      ovarian granulosa cells and the first to demonstrate that LH/hCG regulates the
      expression of select miRNAs, which affect posttranscriptional gene regulation
      within these cells.

PMID- 18716289
TI  - Haploinsufficiency for adrenomedullin reduces pinopodes and diminishes uterine
      receptivity in mice.
AB  - Adrenomedullin (AM) is a multifunctional peptide vasodilator that signals through
      a G-protein-coupled receptor when the receptor, called calcitonin receptor-like
      receptor (CL), is associated with a receptor activity-modifying protein 2
      (RAMP2). We demonstrated previously that haploinsufficieny for each of these
      genes led to reduced maternal fertility, and that even a modest genetic reduction
      of AM peptide caused maternal defects in implantation, placentation, and fetal
      growth. Here, we further demonstrate that Adm(+/-) female mice displayed reduced
      pregnancy success rates that were not caused by defects in folliculogenesis,
      ovulation, or fertilization. The poor fertility of Adm(+/-) female mice could not
      be rescued by transfer of wild-type blastocysts, which suggested an underlying
      defect in uterine receptivity. In fact, we found that Adm, Calcrl, and Ramp2 gene
      expressions are tightly and spatiotemporally regulated in the luminal epithelial
      cells of the uterus during the estrus cycle and the peri-implantation period.
      RAMP3, which also generates an AM receptor when associated with CL, had a
      diametrically opposite expression pattern than that of Adm, Calcrl, and Ramp2 and
      was most robustly induced in the stroma of the uterus. Finally, we discovered
      that Adm(+/-) female mice have a substantially reduced number of pinopodes on the
      uterine luminal epithelial surface, which is indicative and possibly causative of
      the poor uterine receptivity. Taken together, our studies identify a new class of
      pharmacologically tractable proteins that are involved in establishing uterine
      receptivity through the regulation of pinopode formation.

PMID- 18716290
TI  - Regulation of expression of microvillus membrane proteins by estrogen in baboon
      fetal ovarian oocytes.
AB  - We previously demonstrated that the number and height of oocyte microvilli were
      reduced in baboon fetuses deprived of estrogen in utero and restored to normal in
      animals supplemented with estradiol. Phosphorylated ezrin and Na+/H+ exchange
      regulatory factor 1 (NHERF, now termed SLC9A3R1) link f-actin bundles to the
      membrane, whereas alpha-actinin cross-links f-actin to form microvilli.
      Therefore, we determined whether these proteins were expressed in oocytes of the
      fetal baboon ovary and whether expression and/or localization were altered
      between mid and late gestation in association with an increase in estrogen and in
      late gestation in animals in which estrogen was suppressed (>95%) or restored by
      treatment with an aromatase inhibitor with or without estradiol. Expression of
      alpha-actinin was low at mid gestation, increased on the surface of oocytes of
      primordial follicles in late gestation, and was negligible in the ovaries of
      estrogen-suppressed fetuses and normal in animals treated with estrogen. Ezrin
      (total and phosphorylated) and SLC9A3R1 expression was localized to the surface
      of oocytes at mid and late gestation in estrogen-replete baboons and to the
      cytoplasm in late gestation after estrogen suppression. These results are the
      first to show that the fetal baboon oocyte expressed ezrin, SLC9A3R1, and alpha
      actinin, and that these proteins were localized to the oocyte surface consistent
      with their role in microvilli development in epithelial cells. The current study
      also showed that the developmental increase in oocyte expression of alpha-actinin
      is regulated by estrogen and correlated with the estrogen-dependent increase in
      oocyte microvilli demonstrated previously. Therefore, we propose that development
      of oocyte microvilli requires expression of alpha-actinin and that expression of
      alpha-actinin and localization of ezrin-phosphate and SLC9A3R1 to the oocyte
      membrane are regulated by estrogen.

PMID- 18716292
TI  - The relationship between satisfaction with life, ADHD symptoms, and associated
      problems among university students.
AB  - OBJECTIVE: To ascertain whether ADHD symptoms, and associated problems, are
      negatively related to subjective well-being. METHOD: The Satisfaction With Life
      Scale (SWLS) was completed by 369 university students, along with the Reasoning &
      Rehabilitation (R&R) ADHD Training Evaluation (RATE), the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV) Scale for current ADHD symptoms,
      and the Depression Anxiety Stress Scales (DASS). RESULTS: The SWLS was negatively
      correlated with all the other measures, and the strongest correlations were with
      the Total RATE score. A multiple regression analysis showed that the variables in
      the study accounted for 22% and 25% of the variance of the SWLS among males and
      females, respectively. Among males poor social functioning was the best predictor
      of dissatisfaction with life, whereas among females it was poor emotional
      control. CONCLUSION: Both ADHD symptoms and associated problems are significantly
      related to poorer satisfaction with life.

PMID- 18716291
TI  - Identification and characterization of Myosin from rat testicular peritubular
      myoid cells.
AB  - In the mammalian testis, peritubular myoid cells (PMCs) surround seminiferous
      tubules. These cells are contractile, express the cytoskeletal markers of true
      smooth muscle-alpha-isoactin and F-actin-and participate in the contraction of
      seminiferous tubules during the transport of spermatozoa and testicular fluid to
      the rete testis. Myosin from PMCs (PMC-myosin) was isolated from adult rat testis
      and purified by cycles of assembly-disassembly and sucrose gradient
      centrifugation. PMC-myosin was recognized by a monoclonal anti-smooth muscle
      myosin antibody, and the peptide sequence shared partial homology with rat smooth
      muscle myosin-II, MYH11 (also known as SMM-II). Most PMC-myosin (95%) was soluble
      in the PMC cytosol, and purified PMC-myosin did not assemble into filaments in
      the in vitro salt dialysis assay at 4 degrees C, but did at 20 degrees C. PMC
      myosin filaments are stable to ionic strength to the same degree as gizzard MYH11
      filaments, but PMC-myosin filaments were more unstable in the presence of ATP.
      When PMCs were induced to contract by endothelin 1, a fraction of the PMC-myosin
      was found to be involved in the contraction. From these results we infer that
      PMCs express an isoform of smooth muscle myosin-II that is characterized by
      solubility at physiological ionic strength, a requirement for high temperature to
      assemble into filaments in vitro, and instability at low ATP concentrations. PMC
      myosin is part of the PMC contraction apparatus when PMCs are stimulated with
      endothelin 1.

PMID- 18716293
TI  - Images in clinical medicine. Gossypiboma in the pouch of Douglas.

PMID- 18716294
TI  - Health of the nation--coverage for all Americans.

PMID- 18716295
TI  - The partisan divide--the McCain and Obama plans for U.S. health care reform.

PMID- 18716296
TI  - Talking dirty--the politics of clean water and sanitation.

PMID- 18716297
TI  - Preeclampsia and the risk of end-stage renal disease.
AB  - BACKGROUND: It is unknown whether preeclampsia is a risk marker for subsequent
      end-stage renal disease (ESRD). METHODS: We linked data from the Medical Birth
      Registry of Norway, which contains data on all births in Norway since 1967, with
      data from the Norwegian Renal Registry, which contains data on all patients
      receiving a diagnosis of end-stage renal disease (ESRD) since 1980, to assess the
      association between preeclampsia in one or more pregnancies and the subsequent
      development of ESRD. The study population consisted of women who had had a first
      singleton birth between 1967 and 1991; we included data from up to three
      pregnancies. RESULTS: ESRD developed in 477 of 570,433 women a mean (+/-SD) of
      17+/-9 years after the first pregnancy (overall rate, 3.7 per 100,000 women per
      year). Among women who had been pregnant one or more times, preeclampsia during
      the first pregnancy was associated with a relative risk of ESRD of 4.7 (95%
      confidence interval [CI], 3.6 to 6.1). Among women who had been pregnant two or
      more times, preeclampsia during the first pregnancy was associated with a
      relative risk of ESRD of 3.2 (95% CI, 2.2 to 4.9), preeclampsia during the second
      pregnancy with a relative risk of 6.7 (95% CI, 4.3 to 10.6), and preeclampsia
      during both pregnancies with a relative risk of 6.4 (95% CI, 3.0 to 13.5). Among
      women who had been pregnant three or more times, preeclampsia during one
      pregnancy was associated with a relative risk of ESRD of 6.3 (95% CI, 4.1 to
      9.9), and preeclampsia during two or three pregnancies was associated with a
      relative risk of 15.5 (95% CI, 7.8 to 30.8). Having a low-birth-weight or preterm
      infant increased the relative risk of ESRD. The results were similar after
      adjustment for possible confounders and after exclusion of women who had kidney
      disease, rheumatic disease, essential hypertension, or diabetes mellitus before
      pregnancy. CONCLUSIONS: Although the absolute risk of ESRD in women who have had
      preeclampsia is low, preeclampsia is a marker for an increased risk of subsequent
      ESRD.

PMID- 18716298
TI  - Adalimumab with or without methotrexate in juvenile rheumatoid arthritis.
AB  - BACKGROUND: Tumor necrosis factor (TNF) has a pathogenic role in juvenile
      rheumatoid arthritis. We evaluated the efficacy and safety of adalimumab, a fully
      human monoclonal anti-TNF antibody, in children with polyarticular-course
      juvenile rheumatoid arthritis. METHODS: Patients 4 to 17 years of age with active
      juvenile rheumatoid arthritis who had previously received treatment with
      nonsteroidal antiinflammatory drugs underwent stratification according to
      methotrexate use and received 24 mg of adalimumab per square meter of body
      surface area (maximum dose, 40 mg) subcutaneously every other week for 16 weeks.
      We randomly assigned patients with an American College of Rheumatology Pediatric
      30% (ACR Pedi 30) response at week 16 to receive adalimumab or placebo in a
      double-blind fashion every other week for up to 32 weeks. RESULTS: Seventy-four
      percent of patients not receiving methotrexate (64 of 86) and 94% of those
      receiving methotrexate (80 of 85) had an ACR Pedi 30 response at week 16 and were
      eligible for double-blind treatment. Among patients not receiving methotrexate,
      disease flares (the primary outcome) occurred in 43% of those receiving
      adalimumab and 71% of those receiving placebo (P=0.03). Among patients receiving
      methotrexate, flares occurred in 37% of those receiving adalimumab and 65% of
      those receiving placebo (P=0.02). At 48 weeks, the percentages of patients
      treated with methotrexate who had ACR Pedi 30, 50, 70, or 90 responses were
      significantly greater for those receiving adalimumab than for those receiving
      placebo; the differences between patients not treated with methotrexate who
      received adalimumab and those who received placebo were not significant. Response
      rates were sustained after 104 weeks of treatment. Serious adverse events
      possibly related to adalimumab occurred in 14 patients. CONCLUSIONS: Adalimumab
      therapy seems to be an efficacious option for the treatment of children with
      juvenile rheumatoid arthritis. (ClinicalTrials.gov number, NCT00048542.)

PMID- 18716300
TI  - Clinical practice. Idiopathic sudden sensorineural hearing loss.

PMID- 18716299
TI  - Health and economic implications of HPV vaccination in the United States.
AB  - BACKGROUND: The cost-effectiveness of prophylactic vaccination against human
      papillomavirus types 16 (HPV-16) and 18 (HPV-18) is an important consideration
      for guidelines for immunization in the United States. METHODS: We synthesized
      epidemiologic and demographic data using models of HPV-16 and HPV-18 transmission
      and cervical carcinogenesis to compare the health and economic outcomes of
      vaccinating preadolescent girls (at 12 years of age) and vaccinating older girls
      and women in catch-up programs (to 18, 21, or 26 years of age). We examined the
      health benefits of averting other HPV-16-related and HPV-18-related cancers, the
      prevention of HPV-6-related and HPV-11-related genital warts and juvenile-onset
      recurrent respiratory papillomatosis by means of the quadrivalent vaccine, the
      duration of immunity, and future screening practices. RESULTS: On the assumption
      that the vaccine provided lifelong immunity, the cost-effectiveness ratio of
      vaccination of 12-year-old girls was $43,600 per quality-adjusted life-year
      (QALY) gained, as compared with the current screening practice. Under baseline
      assumptions, the cost-effectiveness ratio for extending a temporary catch-up
      program for girls to 18 years of age was $97,300 per QALY; the cost of extending
      vaccination of girls and women to the age of 21 years was $120,400 per QALY, and
      the cost for extension to the age of 26 years was $152,700 per QALY. The results
      were sensitive to the duration of vaccine-induced immunity; if immunity waned
      after 10 years, the cost of vaccination of preadolescent girls exceeded $140,000
      per QALY, and catch-up strategies were less cost-effective than screening alone.
      The cost-effectiveness ratios for vaccination strategies were more favorable if
      the benefits of averting other health conditions were included or if screening
      was delayed and performed at less frequent intervals and with more sensitive
      tests; they were less favorable if vaccinated girls were preferentially screened
      more frequently in adulthood. CONCLUSIONS: The cost-effectiveness of HPV
      vaccination will depend on the duration of vaccine immunity and will be optimized
      by achieving high coverage in preadolescent girls, targeting initial catch-up
      efforts to women up to 18 or 21 years of age, and revising screening policies.

PMID- 18716301
TI  - Images in clinical medicine. Benign mediastinal teratoma.

PMID- 18716302
TI  - Case records of the Massachusetts General Hospital. Case 26-2008. A 26-year-old
      woman with headache and behavioral changes.

PMID- 18716303
TI  - Health of the nation--coverage for all Americans.

PMID- 18716304
TI  - Preeclampsia--a glimpse into the future?

PMID- 18716305
TI  - Human papillomavirus vaccination--reasons for caution.

PMID- 18716306
TI  - Human papillomavirus vaccine in males.

PMID- 18716307
TI  - Age, renal tubular phosphate reabsorption, and serum phosphate levels in adults.

PMID- 18716308
TI  - The hepatopulmonary syndrome.

PMID- 18716309
TI  - Osteoporosis in men.

PMID- 18716310
TI  - Sublingual immunotherapy.

PMID- 18716311
TI  - More on serotonin syndrome associated with triptan monotherapy.

PMID- 18716312
TI  - "Unknown genome" proteomics: a new NADP-dependent epimerase/dehydratase revealed
      by N-terminal sequencing, inverted PCR, and high resolution mass spectrometry.
AB  - We present here a new approach that enabled the identification of a new protein
      from a bacterial strain with unknown genomic background using a combination of
      inverted PCR with degenerate primers derived from N-terminal protein sequences
      and high resolution peptide mass determination of proteolytic digests from two
      dimensional electrophoretic separation. Proteins of the sulfate-reducing
      bacterium Desulfotignum phosphitoxidans specifically induced in the presence of
      phosphite were separated by two-dimensional gel electrophoresis as a series of
      apparent soluble and membrane-bound isoforms with molecular masses of
      approximately 35 kDa. Inverted PCR based on N-terminal sequences and high
      resolution peptide mass fingerprinting by Fourier transform-ion cyclotron
      resonance mass spectrometry provided the identification of a new NAD(P)
      epimerase/dehydratase by specific assignment of peptide masses to a single ORF,
      excluding other possible ORF candidates. The protein identification was
      ascertained by chromatographic separation and sequencing of internal proteolytic
      peptides. Metal ion affinity isolation of tryptic peptides and high resolution
      mass spectrometry provided the identification of five phosphorylations identified
      in the domains 23-47 and 91-118 of the protein. In agreement with the
      phosphorylations identified, direct molecular weight determination of the soluble
      protein eluted from the two-dimensional gels by mass spectrometry provided a
      molecular mass of 35,400 Da, which is consistent with an average degree of three
      phosphorylations.

PMID- 18716313
TI  - Effector proteins of the bacterial pathogen Pseudomonas syringae alter the
      extracellular proteome of the host plant, Arabidopsis thaliana.
AB  - In plants, potential pathogenic bacteria do not enter the host cell. Therefore, a
      large portion of the molecular interaction between microbial pathogen and host
      occurs in the extracellular space. To investigate potential mechanisms of disease
      resistance and susceptibility, we analyzed changes in the extracellular proteome,
      or secretome, using the Arabidopsis-Pseudomonas syringae pathosystem. This system
      provides the possibility to directly compare interactions resulting in basal
      resistance, susceptibility, and gene-specific resistance by using different
      genotypes of Pseudomonas on the same host. After infecting suspension-cultured
      cells of Arabidopsis with the Pseudomonas strain of interest, we isolated protein
      from the cell culture medium representing the secretome. After one-dimensional
      gel separation and in-gel digestion of proteins, we used iTRAQ (isobaric tags for
      relative and absolute quantitation) labeling in conjunction with LC-MS/MS to
      perform relative quantitative comparisons of the secretomes from each of these
      interactions. We obtained quantitative information from 45 Arabidopsis proteins
      that were present in all three biological experiments. We observed complex
      patterns of accumulation, ranging from proteins that decreased in abundance in
      the presence of all three bacterial strains to proteins that specifically
      increased or decreased during only one of the interactions. A particularly
      intriguing result was that the virulent bacteria (e.g. a susceptible interaction)
      caused the extracellular accumulation of a specific subset of host proteins
      lacking traditional signal peptides. These results indicate that the pathogen may
      manipulate host secretion to promote the successful invasion of plants.

PMID- 18716314
TI  - Biomarkers and coagulation tests for assessing the biosimilarity of a generic low
      molecular-weight heparin: results of a study in healthy subjects with enoxaparin.
AB  - Low-molecular-weight heparins (LMWHs) differ considerably in their influence on
      clotting tests and release of tissue factor pathway inhibitor (TFPI).
      Biosimilarity therefore becomes an issue when generic forms of LMWHs are
      developed. So far, no bioequivalence study with a generic LMWH has been reported.
      A generic enoxaparin (test) was compared with the originator (reference) in 20
      volunteers after single-dose subcutaneous administration (40 mg enoxaparin
      sodium, 4000 IU/mL anti-factor Xa (anti-FXa; activity). Target variables were
      anti-FXa and anti-FIIa activity, activated partial thromboplastin time (aPTT),
      prothrombinase-induced clotting time (PiCT), and TFPI over 24 hours. The
      statistical evaluation of the anti-FXa activity profile demonstrated
      bioequivalence of test and reference with confidence intervals of area under the
      plasma concentration-time curve (AUC0-tlast) (93%-99%) and Amax (88%-95%).
      Confidence intervals of AUC(0-tlast) (89%-102%) and Amax (90%-103%) of anti-FIIa
      activity also fulfill bioequivalence criteria. The 90% confidence interval for
      the maximum concentration of TFPI ranged from 90% to 113%. The claim of
      similarity was also supported by aPTT and PiCT profiles. Bioequivalence with the
      originator enoxaparin could be demonstrated by ex vivo inhibition of FXa and FIIa
      activity, by coagulation tests (aPTT and PiCT), and by in vivo release of TFPI.
      Whether such data also prove biosimilarity of the generic enoxaparin needs to be
      determined.

PMID- 18716316
TI  - Cardiolipin increases in chromatophores isolated from Rhodobacter sphaeroides
      after osmotic stress: structural and functional roles.
AB  - Chromatophores isolated from cells of Rhodobacter sphaeroides exposed to
      hypertonic solutions were enriched in cardiolipin (CL). Because CL levels are
      raised by increasing the incubation time of R. sphaeroides in hypertonic
      solutions, it was possible to isolate chromatophores containing different CL
      amounts by starting from cells incubated in hypertonic solutions for different
      times. The functionality and stability of the photosynthetic proteins in
      chromatophore membranes having different CL levels were investigated. Reaction
      center (RC) stabilization with respect to thermal denaturation and photoxidative
      damage was observed by flash photolysis and fluorescence emission experiments in
      CL-enriched chromatophores. To gain detailed information about the structures of
      endogenous CLs, this lipid family was isolated and purified by preparative TLC,
      and characterized by high-resolution mass spectrometry. We conclude that osmotic
      shock can be used as a tool to modulate CL levels in isolated chromatophores and
      to change the composition of the RC lipid annulus, avoiding membrane artifacts
      introduced by the use of detergents.

PMID- 18716315
TI  - Fatty acid-dependent globotriaosyl ceramide receptor function in detergent
      resistant model membranes.
AB  - Glycosphingolipid (GSL) fatty acid strictly regulates verotoxin 1 (VT1) and the
      HIV adhesin, gp120 binding to globotriaosyl ceramide within Gb(3)/cholesterol
      detergent resistant membrane (DRM) vesicle constructs and in Gb(3) water-air
      interface monolayers in a similar manner. VT2 bound Gb(3)/cholesterol vesicles
      irrespective of fatty acid composition, but VT1 bound neither C18 nor
      C20Gb(3)vesicles. C18/C20Gb(3) were dominant negative in mixed Gb(3) fatty acid
      isoform vesicles, but including C24:1Gb(3) gave maximal binding. VT1 bound
      C18Gb(3) vesicles after cholesterol removal, but C20Gb(3)vesicles required
      sphingomyelin in addition for binding. HIV-1gp120 also bound C16, C22, and C24,
      but neither C18 nor C20Gb(3) vesicles. C18 and C20Gb(3) were, in mixtures without
      C24:1Gb(3), dominant negative for gp120 vesicle binding. Gp120/VT1bound C18 and
      C24:1Gb(3) mixtures, although neither isoform bound alone. Monolayer surface
      pressure measurement showed VT1, but not VT2, bound Gb(3) at cellular DRM surface
      pressures, and confirmed loss of VT1 and gp120 (but not VT2) specific C18Gb(3)
      binding. We conclude fatty-acid mediated fluidity within simple model
      GSL/cholesterol DRM can selectively regulate GSL carbohydrate-ligand binding.

PMID- 18716317
TI  - Patterns of USPIO deposition in murine atherosclerosis.

PMID- 18716319
TI  - VEGF-B taken to our hearts: specific effect of VEGF-B in myocardial ischemia.

PMID- 18716320
TI  - NO targets SIRT1: a novel signaling network in endothelial senescence.

PMID- 18716321
TI  - Targeted increases in endothelial cell superoxide anion production stimulate eNOS
      dependent nitric oxide production, not uncoupled eNOS activity.

PMID- 18716322
TI  - Is LDL-C passed its prime? The emerging role of non-HDL, LDL-P, and ApoB in CHD
      risk assessment.

PMID- 18716323
TI  - Scrib regulates PAK activity during the cell migration process.
AB  - Genetic studies have highlighted the key role of Scrib in the development of
      Metazoans. Deficiency in Scrib impairs many aspects of cell polarity and cell
      movement although the mechanisms involved remain unclear. In mammals, Scrib
      belongs to a protein complex containing betaPIX, an exchange factor for
      Rac/Cdc42, and GIT1, a GTPase activating protein for ARF6 implicated in receptor
      recycling and exocytosis. Here we show that the Scrib complex associates with
      PAK, a serine-threonine kinase family crucial for cell migration. PAK colocalizes
      with members of the Scrib complex at the leading edge of heregulin-treated T47D
      breast cancer cells. We demonstrate that the Scrib complex is required for
      epithelial cells and primary mouse embryonic fibroblasts to efficiently respond
      to chemoattractant cues. In Scrib-deficient cells, the pool of cortical PAK is
      decreased, thereby precluding its proper activation by Rac. Loss of Scrib also
      impairs the polarized distribution of active Rac at the leading edge and
      compromises the regulated activation of the GTPase in T47D cells and mouse
      embryonic fibroblasts. These data underscore the role of Scrib in cell migration
      and show the strong impact of Scrib in the function of PAK and Rac, two key
      molecules implicated in this process.

PMID- 18716324
TI  - Sister chromatid cohesion role for CDC28-CDK in Saccharomyces cerevisiae.
AB  - High-fidelity chromosome segregation requires that the sister chromatids produced
      during S phase also become paired during S phase. Ctf7p (Eco1p) is required to
      establish sister chromatid pairing specifically during DNA replication. However,
      Ctf7p also becomes active during G2/M in response to DNA damage. Ctf7p is a
      phosphoprotein and an in vitro target of Cdc28p cyclin-dependent kinase (CDK),
      suggesting one possible mechanism for regulating the essential function of Ctf7p.
      Here, we report a novel synthetic lethal interaction between ctf7 and cdc28.
      However, neither elevated CDC28 levels nor CDC28 Cak1p-bypass alleles rescue ctf7
      cell phenotypes. Moreover, cells expressing Ctf7p mutated at all full- and
      partial-consensus CDK-phosphorylation sites exhibit robust cell growth. These and
      other results reveal that Ctf7p regulation is more complicated than previously
      envisioned and suggest that CDK acts in sister chromatid cohesion parallel to
      Ctf7p reactions.

PMID- 18716325
TI  - The Ku complex in silencing the cryptic mating-type loci of Saccharomyces
      cerevisiae.
AB  - Sir1 establishes transcriptional silencing at the cryptic mating-type loci HMR
      and HML (HM loci) by recruiting the three other Sir proteins, Sir2, -3, and -4,
      that function directly in silenced chromatin. However, SIR1-independent
      mechanisms also contribute to recruiting the Sir2-4 proteins to the HM loci. A
      screen to elucidate SIR1-independent mechanisms that establish HMR silencing
      identified a mutation in YKU80. The role for Ku in silencing both HMR and HML was
      masked by SIR1. Ku's role in silencing the HM loci was distinct from its shared
      role with the nuclear architecture protein Esc1 in tethering the HM loci and
      telomeres to the nuclear periphery. The ability of high-copy SIR4 to rescue HMR
      silencing defects in sir1Delta cells required Ku, and chromatin
      immunoprecipitation (ChIP) experiments provided evidence that Ku contributed to
      Sir4's physical association with the HM loci in vivo. Additional ChIP experiments
      provided evidence that Ku functioned directly at the HM loci. Thus Ku and Sir1
      had overlapping roles in silencing the HM loci.

PMID- 18716326
TI  - Second-order moments of segregating sites under variable population size.
AB  - The identification of genomic regions that have been exposed to positive
      selection is a major challenge in population genetics. Since selective sweeps are
      expected to occur during environmental changes or when populations are colonizing
      a new habitat, statistical tests constructed on the assumption of constant
      population size are biased by the co-occurrence of population size changes and
      selection. To delimit this problem and gain better insights into demographic
      factors, theoretical results regarding the second-order moments of segregating
      sites, such as the variance of segregating sites, have been derived. Driven by
      emerging genomewide surveys, which allow the estimation of demographic
      parameters, a generalized version of Tajima's D has been derived that takes into
      account a previously estimated demographic scenario to test single loci for
      traces of selection against the null hypothesis of neutral evolution under
      variable population size.

PMID- 18716328
TI  - The complementary neighborhood patterns and methylation-to-mutation likelihood
      structures of 15,110 single-nucleotide polymorphisms in the bovine genome.
AB  - Bayesian analysis was performed to examine the single-nucleotide polymorphism
      (SNPs) neighborhood patterns in cattle using 15,110 SNPs, each with a flanking
      sequence of 500 bp. Our analysis confirmed three well-known features reported in
      plants and/or other animals: (1) the transition is the most abundant type of
      SNPs, accounting for 69.8% in cattle; (2) the transversion occurs most frequently
      (38.56%) in cattle when the A + T content equals two at their immediate adjacent
      sites; and (3) C <--> T and A <--> G transitions have reverse complementary
      neighborhood patterns and so do A <--> C and G <--> T transversions. Our study
      also revealed several novel SNP neighborhood patterns that have not been reported
      previously. First, cattle and humans share an overall SNP pattern, indicating a
      common mutation system in mammals. Second, unlike C <--> T/A <--> G and A <-->
      C/G <--> T, the true neighborhood patterns for A <--> T and C <--> G might remain
      mysterious because the sense and antisense sequences flanking these mutations are
      not actually recognizable. Third, among the reclassified four types of SNPs, the
      neighborhood ratio between A + T and G + C was quite different. The ratio was
      lowest for C <--> G, but increased for C <--> T/A <--> G, further for A <--> C/G
      <--> T, and the most for A <--> T. Fourth, when two immediate adjacent sites
      provide structures for CpG, it significantly increased transitions compared to
      the structures without the CpG. Finally, unequal occurrence between A <--> G and
      C <--> T in five paired neighboring structures indicates that the methylation
      induced deamination reactions were responsible for approximately 20% of total
      transitions. In addition, conversion can occur at both CpG sites and non-CpG
      sites. Our study provides new insights into understanding molecular mechanisms of
      mutations and genome evolution.

PMID- 18716327
TI  - Investigation of mcp1 as a quantitative trait gene for prion disease incubation
      time in mouse.
AB  - The genetic basis of prion disease incubation time is principally determined by
      polymorphisms in the prion protein gene, Prnp. However, it is now known that
      other genetic factors are important. Several quantitative trait loci (QTL) have
      been identified across the genome including a broad region of linkage on Mmu11.
      Monocyte chemoattractant protein 1 (MCP-1) maps to this region and has been
      associated with microglial activation and reduced survival in the ME7 mouse
      scrapie model of prion disease. We have identified 10 polymorphisms, 3 of which
      are nonsynonomous, in Mcp1 between "long" (CAST) and "short" (SJL or NZW)
      incubation-time mouse strains. Crosses between these strains and Mcp1(-/-) mice
      inoculated with the Chandler/RML mouse scrapie prion strain formed the basis of a
      quantitative complementation test. In these models loss of Mcp1 did not show an
      increase in incubation time suggesting that the effects of Mcp1 may be specific
      to the ME7 prion strain and that Mcp1 does not contribute to the QTL described on
      Mmu11.

PMID- 18716329
TI  - Maintenance of mitochondrial DNA by the Caenorhabditis elegans ATR checkpoint
      protein ATL-1.
AB  - Here we show that inactivation of the ATR-related kinase ATL-1 results in a
      significant reduction in mitochondrial DNA (mtDNA) copy numbers in Caenorhabditis
      elegans. Although ribonucleotide reductase (RNR) expression and the ATP/dATP
      ratio remained unaltered in atl-1 deletion mutants, inhibition of RNR by RNAi or
      hydroxyurea treatment caused further reductions in mtDNA copy number. These
      results suggest that ATL-1 functions to maintain mtDNA independently of RNR.

PMID- 18716331
TI  - Thelytokous parthenogenesis in unmated queen honeybees (Apis mellifera capensis):
      central fusion and high recombination rates.
AB  - The subspecies of honeybee indigenous to the Cape region of South Africa, Apis
      mellifera capensis, is unique because a high proportion of unmated workers can
      lay eggs that develop into females via thelytokous parthenogenesis involving
      central fusion of meiotic products. This ability allows pseudoclonal lineages of
      workers to establish, which are presently widespread as reproductive parasites
      within the honeybee populations of South Africa. Successful long-term propagation
      of a parthenogen requires the maintenance of heterozygosity at the sex locus,
      which in honeybees must be heterozygous for the expression of female traits.
      Thus, in successful lineages of parasitic workers, recombination events are
      reduced by an order of magnitude relative to meiosis in queens of other honeybee
      subspecies. Here we show that in unmated A. m. capensis queens treated to induce
      oviposition, no such reduction in recombination occurs, indicating that thelytoky
      and reduced recombination are not controlled by the same gene. Our virgin queens
      were able to lay both arrhenotokous male-producing haploid eggs and thelytokous
      female-producing diploid eggs at the same time, with evidence that they have some
      voluntary control over which kind of egg was laid. If so, they are able to
      influence the kind of second-division meiosis that occurs in their eggs post
      partum.

PMID- 18716330
TI  - Multilocus patterns of nucleotide polymorphism and the demographic history of
      Populus tremula.
AB  - I have studied nucleotide polymorphism and linkage disequilibrium using
      multilocus data from 77 fragments, with an average length of fragments of 550 bp,
      in the deciduous tree Populus tremula (Salicaceae). The frequency spectrum across
      loci showed a modest excess of mutations segregating at low frequency and a
      marked excess of high-frequency derived mutations at silent sites, relative to
      neutral expectations. These excesses were also seen at replacement sites, but
      were not so pronounced for high-frequency derived mutations. There was a marked
      excess of low-frequency mutations at replacement sites, likely indicating
      deleterious amino acid-changing mutations that segregate at low frequencies in P.
      tremula. I used approximate Bayesian computation (ABC) to evaluate a number of
      different demographic scenarios and to estimate parameters for the best-fitting
      model. The data were found to be consistent with a historical reduction in the
      effective population size of P. tremula through a bottleneck. The timing inferred
      for this bottleneck is largely consistent with geological data and with data from
      several other long-lived plant species. The results show that P. tremula harbors
      substantial levels of nucleotide polymorphism with the posterior mode of the
      scaled mutation rate, theta = 0.0177 across loci. The ABC analyses also provided
      an estimate of the scaled recombination rate that indicates that recombination
      rates in P. tremula are likely to be 2-10 times higher than the mutation rate.
      This study reinforces the notion that linkage disequilibrium is low and decays to
      negligible levels within a few hundred base pairs in P. tremula.

PMID- 18716332
TI  - Intraspecific phylogeographic genomics from multiple complete mtDNA genomes in
      Atlantic cod (Gadus morhua): origins of the "codmother," transatlantic vicariance
      and midglacial population expansion.
AB  - On the basis of multiple complete mitochondrial DNA genome sequences, we describe
      the temporal phylogeography of Atlantic cod (Gadus morhua), a lineage that has
      undergone a complex pattern of vicariant evolution, postglacial demographic
      shifts, and historic sharp population declines due to fishing and/or
      environmental shifts. Each of 32 fish from four spawning aggregations from the
      northwest Atlantic and Norway has a unique mtDNA sequence, which differs by 6-60
      substitutions. Phylogenetic analysis identifies six major haplogroups that range
      in age from 37 to 75 KYA. The widespread haplotype identified by previous single
      locus analyses at the center of a "star phylogeny" is shown to be a paraphyletic
      assemblage of genome lineages. The coalescent that includes all cod occurs 162
      KYA. The most basal clade comprises two fish from the western Atlantic. The most
      recent superclade that includes all fish examined from Norway, and which includes
      84% of all fish examined, dates to 128 KYA at the Sangamon/Wurm interglacial,
      when ocean depths on continental shelves would have favored transcontinental
      movement. The pairwise mismatch distribution dates population expansion of this
      superclade to the middle of the Wisconsinan/Weichsel glaciation 59 KYA, rather
      than to a postglacial emergence from a marine refugium 12 KYA, or to more recent
      historic events. We discuss alternative scenarios for the expansion and
      distribution of the descendants of the "codmother" in the North Atlantic.
      Mitochondrial phylogenomic analyses generate highly resolved trees that enable
      fine-scale tests of temporal hypotheses with an accuracy not possible with single
      locus methods.

PMID- 18716333
TI  - Hitchhiking both ways: effect of two interfering selective sweeps on linked
      neutral variation.
AB  - The neutral polymorphism pattern in the vicinity of a selective sweep can be
      altered by both stochastic and deterministic factors. Here, we focus on the
      impact of another selective sweep in the region of influence of a first one. We
      study the signature left on neutral polymorphism by positive selection at two
      closely linked loci, when both beneficial mutations reach fixation. We show that,
      depending on the timing of selective sweeps and on their selection coefficients,
      the two hitchhiking effects can interfere with each other, leading to less
      reduction in heterozygosity than a single selective sweep of the same magnitude
      and more importantly to an excess of intermediate-frequency variants relative to
      neutrality under some parameter values. This pattern can be sustained and
      potentially alter the detection of positive selection, including by provoking
      spurious detection of balancing selection. In situations where positive selection
      is suspected a priori at several closely linked loci, the polymorphism pattern in
      the region may also be informative about their selective histories.

PMID- 18716334
TI  - Natural genetic variation of Arabidopsis thaliana is geographically structured in
      the Iberian peninsula.
AB  - To understand the demographic history of Arabidopsis thaliana within its native
      geographical range, we have studied its genetic structure in the Iberian
      Peninsula region. We have analyzed the amount and spatial distribution of A.
      thaliana genetic variation by genotyping 268 individuals sampled in 100 natural
      populations from the Iberian Peninsula. Analyses of 175 individuals from 7 of
      these populations, with 20 chloroplast and nuclear microsatellite loci and 109
      common single nucleotide polymorphisms, show significant population
      differentiation and isolation by distance. In addition, analyses of one genotype
      from 100 populations detected significant isolation by distance over the entire
      Iberian Peninsula, as well as among six Iberian subregions. Analyses of these 100
      genotypes with different model-based clustering algorithms inferred four genetic
      clusters, which show a clear-cut geographical differentiation pattern. On the
      other hand, clustering analysis of a worldwide sample showed a west-east Eurasian
      longitudinal spatial gradient of the commonest Iberian genetic cluster. These
      results indicate that A. thaliana genetic variation displays significant regional
      structure and consistently support the hypothesis that Iberia has been a glacial
      refugium for A. thaliana. Furthermore, the Iberian geographical structure
      indicates a complex regional population dynamics, suggesting that this region
      contained multiple Pleistocene refugia with a different contribution to the
      postglacial colonization of Europe.

PMID- 18716335
TI  - A male-specific fatty acid omega-hydroxylase, SXE1, is necessary for efficient
      male mating in Drosophila melanogaster.
AB  - In Drosophila, sexual differentiation, physiology, and behavior are thought to be
      mediated by numerous male- and female-specific effector genes whose expression is
      controlled by sex-specifically expressed transcriptional regulators. One such
      downstream effector gene, sex-specific enzyme 1 (sxe1, cyp4d21), has been
      identified in a screen for genes with sex-biased expression in the head. Sxe1 was
      also identified in another screen as a circadian regulated gene. Here, we
      analyzed the spatial and temporal regulation of sxe1 and identified a function
      for this gene in male courtship. We show that male-specific transcriptional
      regulator DSX(M) and the clock genes are necessary for cycling of sxe1 mRNA
      during the diurnal cycle. Similar to sxe1 mRNA, expression of SXE1 protein
      oscillates in a diurnal fashion, with highest protein levels occurring around
      midnight. SXE1 protein expression is restricted to nonneuronal cells associated
      with diverse sensory bristles of both the chemo- and mechanosensory systems.
      Suppression or knockout of sxe1 significantly reduces mating success throughout
      the diurnal cycle. Finally, the metabolomic profile of wild-type and sxe1 mutant
      males revealed that sxe1 likely functions as a fatty acid omega-hydroxylase,
      suggesting that male courtship and mating success is mediated by small compounds
      generated by this enzyme.

PMID- 18716336
TI  - Quantitative trait loci affecting phenotypic plasticity and the allometric
      relationship of ovariole number and thorax length in Drosophila melanogaster.
AB  - Environmental factors during juvenile growth such as temperature and nutrition
      have major effects on adult morphology and life-history traits. In Drosophila
      melanogaster, ovary size, measured as ovariole number, and body size, measured as
      thorax length, are developmentally plastic traits with respect to larval
      nutrition. Herein we investigated the genetic basis for plasticity of ovariole
      number and body size, as well the genetic basis for their allometric relationship
      using recombinant inbred lines (RILs) derived from a natural population in
      Winters, California. We reared 196 RILs in four yeast concentrations and measured
      ovariole number and body size. The genetic correlation between ovariole number
      and thorax length was positive, but the strength of this correlation decreased
      with increasing yeast concentration. Genetic variation and genotype-by
      environment (G x E) interactions were observed for both traits. We identified
      quantitative trait loci (QTL), epistatic, QTL-by-environment, and epistatic-by
      environment interactions for both traits and their scaling relationships. The
      results are discussed in the context of multivariate trait evolution.

PMID- 18716337
TI  - Effects of spatially varying selection on nucleotide diversity and linkage
      disequilibrium: insights from deer mouse globin genes.
AB  - An important goal of population genetics is to elucidate the effects of natural
      selection on patterns of DNA sequence variation. Here we report results of a
      study to assess the joint effects of selection, recombination, and gene flow in
      shaping patterns of nucleotide variation at genes involved in local adaptation.
      We first describe a new summary statistic, Z(g), that measures the between-sample
      component of linkage disequilibrium (LD). We then report results of a multilocus
      survey of nucleotide diversity and LD between high- and low-altitude populations
      of deer mice, Peromyscus maniculatus. The multilocus survey included two closely
      linked alpha-globin genes, HBA-T1 and HBA-T2, that underlie adaptation to
      different elevational zones. The primary goals were to assess whether the alpha
      globin genes exhibit the hallmarks of spatially varying selection that are
      predicted by theory (i.e., sharply defined peaks in the between-population
      components of nucleotide diversity and LD) and to assess whether peaks in
      diversity and LD may be useful for identifying specific sites that distinguish
      selectively maintained alleles. Consistent with theoretical expectations, HBA-T1
      and HBA-T2 were characterized by highly elevated levels of diversity between
      populations and between allele classes. Simulation and empirical results indicate
      that sliding-window analyses of Z(g) between allele classes may provide an
      effective means of pinpointing causal substitutions.

PMID- 18716338
TI  - A molecular selection index method based on eigenanalysis.
AB  - The traditional molecular selection index (MSI) employed in marker-assisted
      selection maximizes the selection response by combining information on molecular
      markers linked to quantitative trait loci (QTL) and phenotypic values of the
      traits of the individuals of interest. This study proposes an MSI based on an
      eigenanalysis method (molecular eigen selection index method, MESIM), where the
      first eigenvector is used as a selection index criterion, and its elements
      determine the proportion of the trait's contribution to the selection index. This
      article develops the theoretical framework of MESIM. Simulation results show that
      the genotypic means and the expected selection response from MESIM for each trait
      are equal to or greater than those from the traditional MSI. When several traits
      are simultaneously selected, MESIM performs well for traits with relatively low
      heritability. The main advantages of MESIM over the traditional molecular
      selection index are that its statistical sampling properties are known and that
      it does not require economic weights and thus can be used in practical
      applications when all or some of the traits need to be improved simultaneously.

PMID- 18716339
TI  - Enzymatic debriding agents: an evaluation of the medical literature.
AB  - Although debridement is an essential part of wound care, information to guide
      evidence-based decisions is limited in the literature. Assuming studies to
      ascertain the effectiveness of pharmaceutically based enzymatic debridement
      products are more prolific than studies using nonpharmaceutical debridement
      options, a literature review was conducted to provide an evidence base to justify
      current wound care practice. Information on collagenase- and papain-urea-based
      products was reviewed with emphasis on their functional components, mechanisms of
      action, and patient considerations. The Medline Database, Cochrane Database of
      Systematic Reviews, InfoPOEMs, Institute for Clinical Systems Improvement,
      National Guideline Clearinghouse, and Primary Care Clinical Practice Guidelines
      were searched for documents published between 1967 and 2007 using the following
      terms: enzymatic debridement, collagenase, papain-urea, papain-urea chlorophyllin
      copper complex, wounds, and diabetic foot wounds. Sixteen of of 44 relevant
      citations obtained fit the established criteria for readability, accuracy,
      reliability and validity of information. Four of the 16 studies included a
      control treatment, the external validity of 13 studies was limited due to small
      sample size, and only four studies reported a statistically significant
      difference in treatment outcome. Predicted bias and publication bias were common.
      Of the studies detailed herein, three qualified as A level, 13 qualified as B
      level, and none were considered to provide C level evidence. Although clinicians
      can glean practical information from the homogenized findings regarding patient
      demographics, wound type, and therapeutic goals, future studies designed to meet
      the criteria of level A evidence are needed to provide evidence for the use of
      enzymatic debridement agents.

PMID- 18716340
TI  - Improving wound care simulation with the addition of odor: a descriptive, quasi
      experimental study.
AB  - Improving problem-solving skills and expertise in complex clinical care provision
      requires engaging students in the learning process--a challenging goal when
      clinical practicums and supervisors are limited. High-fidelity simulation has
      created many new opportunities for educating healthcare professionals. Because
      addressing malodorous wounds is a common problem that may be difficult to
      "teach," a descriptive, quasi-experimental simulation study was conducted.
      Following completion of a wound care simulation and Laerdal's Simulation
      Experience Evaluation Tool by 137 undergraduate nursing students, 50 control
      subjects were randomly selected and 49 volunteer students (experimental group)
      participated in a wound care simulation after one of three cheeses with a strong
      odor was added to simulate a malodorous wound. Compared to the control group,
      study group responses were significantly better (P <0.001) for eight of the 12
      survey variables tested and indicated the addition of odor was beneficial in
      enhancing the perceived realism and value of the simulation. Students responded
      that the addition of odor in the simulation laboratory improved realism and they
      felt better prepared to handle malodorous wounds in a clinical setting. An
      unanticipated outcome was the enhanced feeling of involvement associated with
      paired care teams as opposed to working in larger groups. The results of this
      study indicate that wound care education outcomes improve when nursing students
      are able to practice using a multi-sensorial wound care simulation model.

PMID- 18716341
TI  - Iliopsoas muscle abscess secondary to sacral pressure ulcer treated with computed
      tomography-guided aspiration and continuous irrigation: a case report.
AB  - Iliopsoas abscess is an aggressive infection usually associated with Crohn's
      disease, spinal tuberculosis, a septic hip joint (including hip replacement), and
      spinal cord injury. It rarely occurs secondary to sacral pressure ulcer. The
      infection requires immediate surgical debridement or drainage. The case of a 78
      year-old woman with high fever and severe inflammation caused by iliopsoas
      abscess secondary to a sacral pressure ulcer is reported. The patient was treated
      with a computed tomography-guided aspiration; Escherichia coli was isolated from
      the pus of the ulcer and abscess sites. The abscess completely resolved within 2
      weeks but another abscess developed. Following surgery and daily cleansing, the
      drainage tube was removed after 1 week. Once granulation tissue formation was
      sufficient, the sacral wound was covered with gluteal fasciocutaneous rotation
      flaps 6 weeks after admission. The wounds closed and the patient made a full
      recovery within 2 months. Early recognition followed by immediate drainage of pus
      and appropriate antibiotic therapy are essential to the treatment of these
      wounds. Experience confirms that computed tomography-guided aspiration is useful
      and may be less damaging than surgical debridement.

PMID- 18716342
TI  - Acoustic pressure wound therapy to facilitate granulation tissue in sacral
      pressure ulcers in patients with compromised mobility: a case series.
AB  - Electrical stimulation and other modalities are recommended for treatment of
      pressure ulcers in spinal cord injury patients but their use may be limited by
      clinical contraindications such as necrosis and infection. Acoustic pressure
      wound therapy can be used to address infection and has no known contraindications
      related to wound status. A retrospective nonconsecutive study was conducted
      involving five inpatients with sacral pressure ulcers and compromised mobility
      (spinal cord injury, ventilator/mobility dependency, or persistent vegetative
      state) treated with acoustic pressure wound therapy three times per week, 4 to 6
      minutes per session, for 5 weeks to 5.5 months. Acoustic pressure wound therapy
      was administered until necrotic tissue was removed, granulation was complete,
      drainage resolved to moderate levels, and wound size was compatible with
      indications for high-voltage electrical stimulation. Within 1 to 4 weeks of
      starting acoustic pressure wound therapy, four out of five wounds with
      substantial yellow slough or eschar demonstrated 100% granulation tissue and
      wound area and volume decreased 71% to 97% and 75% to 99%, respectively.
      Subsequent treatments included electrical stimulation alone (three patients) or
      in conjunction with negative pressure wound therapy (one patient), and silver
      foam (one patient). Acoustic pressure wound therapy was found to be an effective
      option in preparing wounds for subsequent therapy.

PMID- 18716344
TI  - Comment on 'measurement of activity concentrations of natural radionuclides in
      the topsoil of IITA Ibadan by gamma-ray spectrometry'.

PMID- 18716346
TI  - Uncertainty evaluation and expression in dose and risk assessment.

PMID- 18716348
TI  - Some recollections of UNSCEAR.

PMID- 18716349
TI  - Sweet preference, obesity and genetic polymorphism of leptin and the leptin
      receptor.

PMID- 18716350
TI  - Does genetic variation in the leptin receptor influence the sympathetic tone in
      obesity?

PMID- 18716351
TI  - Matrix metalloproteinases in hypertensive heart disease: new mechanistic
      insights.

PMID- 18716352
TI  - Characteristics of young-onset white coat hypertension identified by targeted
      screening for hypertension at a university health check-up.
AB  - Previously we estimated the prevalence of essential hypertension (EH) as around
      0.1% and suggested that male gender, obesity, and strong genetic background
      (hypertension in parents) were risk factors for EH in a young population aged
      less than 30 based on targeted screening for hypertension at a university health
      check-up. This study also revealed a high incidence of white coat hypertension
      (WCH) in university students, and thus, we continued this screening for four
      consecutive years, and examined the prognosis and clinical characteristics of
      young-onset WCH. Three occasions of casual blood pressure (BP) measurement and
      additional home BP measurement revealed 72 WCH and 15 EH students (all males)
      during the 4-year study period. None of the WCH students had elevated home BP to
      the level of hypertension during their stay at university, and 26 out of 38 WCH
      students participating screening in the following years showed normal casual BP.
      Although WCH students showed a significantly higher pulse rate than controls, WCH
      could not be fully differentiated from EH either by pulse rate or by correlation
      between casual BP value and pulse rate. These findings indicate the requirement
      of longer follow-up after graduation to determine the prognosis of young-onset
      WCH, though EH and WCH in the young population share the same risk factors and,
      possibly, autonomic nervous system dysfunction. Since diagnosis of WCH has
      limited importance for university students, screening of EH following a general
      health check-up would elevate the clinical validity of casual BP measurement at
      the university.

PMID- 18716353
TI  - Leptin gene and leptin receptor gene polymorphisms are associated with sweet
      preference and obesity.
AB  - Leptin is an adipocyte-secreted hormone that regulates food intake and body
      weight, and that was recently reported to suppress sweet sensitivity in an animal
      model. We investigated the associations among sweet preference, obesity, and
      polymorphisms of the leptin gene (LEP) or leptin receptor gene (LEPR). A total of
      3,653 residents randomly selected from among the citizens of Suita City, Osaka,
      Japan were enlisted as subjects, in whom we investigated sweet preference,
      clinical characteristics, including obesity and serum leptin level, and the
      polymorphisms of LEP and LEPR (G-2548A and A19G for LEP; R109K, R223Q, and
      rs3790439 for LEPR). We determined the associations among the parameters using
      logistic regression analysis, in order to consider potential confounding factors
      for sweet preference and/or obesity. The LEP A19G and LEPR R109K polymorphisms
      were associated with sweet preference, whereas the serum leptin level was not.
      Further, the LEPR 109KK genotype was found to be associated with obesity along
      with sweet preference. In conclusion, our results are the first to show
      associations of LEP and LEPR polymorphisms with sweet preference, and may provide
      useful information for diagnosis and treatment of lifestyle-related diseases.

PMID- 18716354
TI  - The predictive value of brachial-ankle pulse wave velocity in coronary
      atherosclerosis and peripheral artery diseases in urban Chinese patients.
AB  - Coronary artery disease (CAD) is one of the most common diseases throughout the
      world. To investigate the relationship between brachial-ankle pulse wave velocity
      (baPWV) and arterial atherosclerosis and peripheral artery disease (PAD) and its
      potential diagnostic value in diagnosing arterial sclerosis, a self-designed
      questionnaire and special machine designed by Colin Corp., Ltd. were implemented
      to measure the level of baPWV and the ankle-brachial index (ABI) and their
      relations to coronary and peripheral artery atherosclerosis. The results showed
      that baPWV and ABI were equally effective at predicting stenosis of the coronary
      arteries and stenosis of the arteries of the lower extremities. Different levels
      of baPWV with corresponding ABI can express different degrees of arterial
      sclerosis and peripheral artery lesion to a certain extent. Measurement of both
      baPWV and ABI is thus highly recommended in clinical investigation. Arterial wave
      reflection is a major determinant of left ventricular function, coronary
      perfusion, and cardiovascular risk. We investigated whether arterial wave
      velocity can detect atherosclerosis of the coronary arteries and peripheral
      arteries in patients with documented coronary artery diseases. Our goal was to
      investigate the relationship between baPWV and arterial atherosclerosis and PAD
      and their potential diagnostic value. Two hundred and seventy-two patients
      ranging in age from 45-92 years (mean: 66.87+/-11.42 years) were selected from
      the Department of Cardiology of our hospital. A carefully designed questionnaire
      was used to gather baseline data for each patient. All patients underwent
      cardioangiography and were divided into four groups according to their Gensini
      scores: a control group, and groups with a mild, moderate, or severe degree of
      stenosis. One hundred and five of these patients simultaneously underwent
      angiography of the lower extremities and were divided into four groups according
      to the degree of artery stenosis: a control group, and groups with a mild,
      moderate, or severe degree of stenosis. Grouping of baPWV levels was made
      according to Japanese surveys. Bilateral baPWV and ABI were measured using non
      invasive arterial atherosclerosis measuring equipment. In the coronary artery
      groups based on Gensini score, ABI in the group with a high degree of stenosis
      was significantly lower than that in the control and moderate stenosis groups,
      while the baPWV was significantly higher than that in the control and mild
      stenosis groups. In the grouping of baPWV levels, it was indicated that the ABI
      level was significantly different between each group. The ABI<0.9 in groups with
      baPWV<1,400 cm/s and >2,100 cm/s was higher than that in other groups. In the
      grouping by angiography of the lower extremities, the ABI level was decreased
      with increasing degree of artery stenosis while the baPWV levels were increased
      under the same circumstance (p<0.05 or p<0.01). Logistic regression analysis
      indicated that relatively low ABI, high baPWV, abnormal fasting blood glucose,
      and smoking were independent risk factors for the development of cardiovascular
      diseases. The simultaneous measurement of bilateral baPWV and ABI using the newly
      developed equipment presented herein is highly recommended, and should play an
      important role in predicting the possibility of cardiovascular diseases and the
      degree of coronary artery lesions. It is important to note that baPWV is not only
      one of the risk factors in the presence of coronary stenosis, but also a
      substitute index of target-organ damage, another parameter in predicting PAD. The
      current study indicated that a baPWV>1,800 cm/s often follows a severe coronary
      artery event, while baPWV>2,100 cm/s may be related to potential PAD. baPWV
      measurement is helpful to make new standard of diagnosing PAD in Chinese cohorts.

PMID- 18716355
TI  - Overweight body mass index classification modifies arterial stiffening associated
      with weight gain in healthy middle-aged Japanese men.
AB  - The present study was conducted to clarify whether body mass index (BMI
      [kg/m(2)]) classifications (i.e., without excess weight, overweight, and obese)
      modify the rate of progression of arterial stiffening, a cardiovascular risk
      factor associated with weight gain. A 3-year observational study was conducted in
      2,080 healthy middle-aged Japanese men (aged 42+/-10 years). Brachial-ankle pulse
      wave velocity (baPWV) was measured at the beginning and end of the study period.
      In overweight subjects (30>BMI>or=25), the estimated annual rate of increase of
      baPWV (ARbaPWV) in subjects with weight gain (>or=5% weight gain; ARbaPWV, 21.8+/
      4.4 cm/s/year) was significantly higher than in those without weight gain (<5%
      weight gain; ARbaPWV, 12.5+/-1.6 cm/s/year), after adjustments for changes in
      blood pressure and other variables (p<0.05). This change was not observed in
      subjects without excess weight (BMI<25) or in obese subjects (BMI>or=30). The
      increase in the ARbaPWV associated with weight gain in the overweight group was
      also higher than that in the without excess body weight or obese groups. Our
      study revealed that the BMI classifications modified the annual rate of increase
      in arterial stiffening associated with weight gain. Weight gain seemed to
      accelerate arterial stiffening in overweight subjects, but not in subjects
      without excess weight. The weight gain in overweight subjects seemed to worsen
      the cardiovascular risk related to arterial stiffness in middle-aged healthy
      Japanese men. Thus, the prevention of weight gain should be emphasized in
      overweight subjects.

PMID- 18716356
TI  - Leptin-receptor polymorphisms relate to obesity through blunted leptin-mediated
      sympathetic nerve activation in a Caucasian male population.
AB  - Leptin plays a key role in the regulation of body weight through the sympathetic
      nervous system; however, the contributions of leptin-receptor polymorphisms to
      obesity and sympathetic nerve activity have not been fully clarified. In the
      present study, we examined the relationships between leptin-receptor
      polymorphisms, plasma leptin and whole-body norepinephrine (NE) spillover as an
      index of sympathetic nerve activity in a Caucasian male cohort. In 129 young
      healthy normotensive men with a wide range of body mass index (BMI) (19.4-39.5
      kg/m(2)), we measured leptin-receptor polymorphisms (Gln223Arg, Lys656Asn, and
      Lys109Arg), plasma leptin levels, whole-body NE spillover, whole-body NE
      clearance, BMI and blood pressure (BP) levels in the supine position after
      overnight fasting. Overweight-obese (BMI>or=25 kg/m(2)) subjects had
      significantly greater BMI, BP levels, plasma leptin and whole-body NE spillover
      compared to lean (BMI<25 kg/m(2)) subjects, but the NE clearance was similar.
      Overweight-obese subjects had significantly higher frequencies of the Arg223
      allele and the Arg223 homozygous allele of Gln223Arg and the Asn656 allele of
      Lys656Asn compared to lean subjects. Subjects carrying the Arg223 homozygous or
      the Asn656 allele had higher levels of plasma leptin, BMI, waist circumference,
      and waist-to-hip ratio, but significantly less whole-body NE spillover,
      especially when they were also overweight-obese. BP levels and whole-body NE
      clearance were similar between subjects with and without the Arg223 homozygous or
      Asn656 allele. No differences were found in the distributions of the Arg109
      allele of Lys109Arg polymorphism between nonobese and overweight-obese subjects.
      In addition, BMI, BP, plasma leptin levels, whole-body NE spillover and whole
      body NE clearance were similar between those with and without the Arg109 allele.
      Together, these findings demonstrate that leptin-receptor polymorphisms were
      related to the incidence of obesity in a Caucasian male population. These
      polymorphisms were accompanied by high plasma leptin levels (leptin resistance)
      and lower whole-body plasma NE spillover (blunted sympathetic nerve activity). We
      therefore hypothesize that leptin-receptor play a role in the development of
      obesity through leptin resistance and blunted leptin-mediated sympathetic nerve
      activity.

PMID- 18716357
TI  - Chronic Kidney Disease Japan Cohort (CKD-JAC) study: design and methods.
AB  - The prevalence and incidence of end-stage renal disease (ESRD) in Japan are the
      highest and the third highest, respectively, in the world, while the incidence of
      cardiac death in Japan is the lowest among developed countries. A recent study
      showed that the prevalence of chronic kidney disease (CKD), defined as an
      estimated glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m(2), is
      extremely high in Japan, about 20% of the adult population. However, the risk of
      ESRD and cardiovascular disease (CVD) in the CKD population has not been
      determined nationwide. For this observational study, we will establish a Chronic
      Kidney Disease Japan Cohort (CKD-JAC) by enrolling 3,000 patients with CKD in 17
      clinical centers around Japan, which will be used to determine the incidence of
      ESRD and CVD in Japanese CKD patients. Risk factors associated with the
      development of CVD will also be examined. Comorbidity of diabetes in CKD patients
      will be analyzed to determine whether it is a risk for rapid progression of CKD
      and high incidence of CVD. In addition, we will study whether the burden of CKD
      decreases the QOL of patients, and increases hospitalization or health resource
      utilization. Insights from the CKD-JAC study will provide a basis for future
      interventional trials focused on reducing the burden of ESRD and CVD in patients
      with CKD in Japan.

PMID- 18716358
TI  - Aortic pressure augmentation as a marker of cardiovascular risk in obstructive
      sleep apnea syndrome.
AB  - Obstructive sleep apnea syndrome (OSAS) is associated with increases in
      cardiovascular morbidity and mortality. Vascular changes in individuals with OSAS
      have not been fully elucidated, however. The possible impact of OSAS on the
      extent of aortic pressure augmentation (AG), an indicator of cardiovascular risk,
      was investigated. Forty-five consecutive male patients aged 35 to 78 years
      (56.0+/-9.6 years) who were referred to the sleep clinic of Nagoya University
      Hospital for screening and treatment of OSAS and 71 age-matched healthy men were
      enrolled in the study. AG was derived from the pressure waveform measured at the
      radial artery by applanation tonometry. The number of apnea and hypopnea episodes
      per hour (apnea-hypopnea index [AHI]) was determined by standard polysomnography.
      AG was significantly greater in OSAS patients than in controls (9.0+/-4.1 vs.
      6.4+/-3.4 mmHg, p<0.001), and it was significantly reduced in 19 OSAS patients
      treated with continuous positive airway pressure. AG was also significantly
      correlated with the AHI (r=0.562, p<0.001) and age (r=0.356, p=0.016) but not
      with the serum concentrations of low and high density lipoprotein-cholesterol,
      triglyceride, or glycosylated hemoglobin. Stepwise multiple regression analysis
      revealed that the AHI was the most significant contributing factor to the
      increased AG in OSAS patients (beta=0.109, r=0.530, p<0.001). OSAS may thus have
      an adverse effect on vascular function that can be ameliorated by appropriate
      treatment.

PMID- 18716359
TI  - Difference between home and office blood pressures among treated hypertensive
      patients from the Japan Home versus Office Blood Pressure Measurement Evaluation
      (J-HOME) study.
AB  - This study sought to clarify the factors associated with the magnitude of the
      difference between home and office blood pressures in treated hypertensive
      patients. Study subjects consisted of 3,308 essential hypertensive patients (mean
      age, 66 years; males, 44%) receiving antihypertensive treatment in primary care
      settings in Japan. Patients were classified into 3 groups (the home effect group,
      small difference group, and office effect group) according to tertiles of the
      magnitude of the office-home systolic blood pressure difference. Compared to the
      other two groups, the home effect group patients were significantly and
      independently older, were more often habitual drinkers, had a greater family
      history of cerebrovascular disease or personal history of ischemic heart disease,
      and were prescribed a greater number of antihypertensive drugs, non-amlodipine
      calcium channel blockers, and alpha-blockers as antihypertensive drugs. Compared
      to the other two groups, the office effect group patients were significantly and
      independently younger, included more females, less frequently had a family
      history of cerebrovascular disease or personal history of ischemic heart disease,
      and were less often prescribed alpha-blockers as antihypertensive drugs. The
      characteristics of home effect group patients and the factors negatively
      affecting the blood pressure difference were the same. Among treated hypertensive
      patients, compared to patients in the other groups, office effect group patients
      had a lower-risk profile, whereas home effect group patients had a higher-risk
      profile. These predictive factors might be useful clinically to help identify
      patients who may have a large difference between home and office blood pressures.

PMID- 18716360
TI  - Continued high risk of stroke in treated hypertensives in a general population:
      the Jichi Medical School Cohort study.
AB  - Although it is confirmed that antihypertensive treatment for hypertension (HT)
      reduces stroke, it is uncertain whether the risk of stroke in controlled
      hypertensives is as low as that in normotensives. To address this question, we
      examined the risk of stroke in hypertensives with or without antihypertensive
      treatment in the general population. A total of 11,103 men and women were
      enrolled in for this multi-center, population-based cohort study. Subjects were
      divided into three categories: normotensives (blood pressure <140/90 mmHg),
      treated hypertensives, and non-treated hypertensives (blood pressure >or=140/90
      mmHg without antihypertensive treatment). The treated hypertensives were divided
      into controlled and uncontrolled HT groups. The non-treated hypertensives were
      also divided into two groups: mild HT, and moderate or severe HT. The mean follow
      up duration was 10.7 years. Risk of all stroke was significantly higher in the
      hypertensives than in the normotensives (treated HT: hazard ratio=3.00 in men and
      3.34 in women, 95% confidence interval=2.00-4.51 in men and 2.29-4.87 in women;
      non-treated HT: 2.56, 1.83-3.57 in men and 1.93, 1.35-2.76 in women). Risk of
      stroke in controlled treated hypertensives was about three times as high as that
      in normotensives (2.96, 1.66-5.26 in men and 3.69, 2.20-6.17 in women). Risk of
      stroke was about 2.5 times higher in individuals with hyperglycemia than in those
      with normoglycemia among both treated hypertensive men and women. In conclusion,
      compared with normotensives, hypertensives of all categories had a significantly
      higher risk of stroke. Residual confounding might have affected the result that
      risk of stroke was higher in controlled treated HT than in non-treated mild HT.
      Moreover, it is important to control blood pressure and blood glucose in
      hypertensives in order to reduce the risk of stroke.

PMID- 18716361
TI  - Comparison of arterial functional evaluations as a predictor of cardiovascular
      events in hypertensive patients: the Non-Invasive Atherosclerotic Evaluation in
      Hypertension (NOAH) study.
AB  - Increased arterial stiffness and impaired vasodilator response have been
      associated with cardiovascular events in high-risk patients. However, whether
      arterial changes predict the occurrence of hypertensive complications is still
      unclear. Therefore, we designed a hospital-based cohort study to examine the
      prognostic impact of arterial functional changes on stroke and cardiovascular
      diseases in hypertensive patients. The study employed 676 patients with essential
      hypertension. At baseline, we evaluated second-derived photoplethysmography,
      carotid-femoral pulse wave velocity (PWV), and forearm reactive hyperemia. We
      classified subjects into quartile groups according to the baseline measurements
      of these evaluations and assessed the ability of each measure to predict stroke
      and cardiovascular diseases (CVD). During a mean follow-up period of 57 months,
      52 strokes, 40 CVD, and 22 deaths were recorded. Kaplan-Meier analysis revealed
      that patients in the highest quartile of PWV showed a higher frequency of stroke
      and CVD (p<0.0001) and total mortality (p=0.0016), and those in the highest
      quartile of reactive hyperemia showed a lower frequency of stroke and CVD
      (p=0.0415). A Cox hazard model identified that classification in the highest
      quartile of PWV (relative risk=2.717) and reactive hyperemia (0.416) were
      predictive of stroke and CVD after adjustment for other risk factors. In subjects
      who did not experience stroke or CVD before the study period (n=558), only PWV
      was related with the occurrence of stroke and CVD based on the Cox hazard model.
      In conclusion, increased aortic stiffness evaluated by PWV is more prognostic of
      cardiovascular events in hypertensive patients than several non-invasive
      atherosclerotic evaluations.

PMID- 18716362
TI  - Combination therapy with renin-angiotensin system inhibitors and the calcium
      channel blocker azelnidipine decreases plasma inflammatory markers and urinary
      oxidative stress markers in patients with diabetic nephropathy.
AB  - A calcium channel blocker (CCB), azelnidipine (AZ), is reported to inhibit
      oxidative stresses, particularly when administered under blockade of the renin
      angiotensin system (RAS). The purpose of this study was to investigate whether AZ
      inhibits oxidative stresses more potently than other CCBs under blockade of RAS
      and exerts renoprotection in type 2 diabetic nephropathy. Subjects were
      hypertensive type 2 diabetics with nephropathy, taking RAS inhibitors. The
      patients were randomly assigned to two groups, an AZ group (n=21, 16 mg/d) and a
      nifedipine-CR (NF) group (n=17, 40 mg/d). The plasma levels of monocyte
      chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), high-sensitive C
      reactive protein (hsCRP), adiponectin and tumor necrosis factor-alpha
      (TNF(alpha)), the urinary excretion of 8-epi-prostaglandin F(2alpha) (8-epi
      PGF(2alpha)) and 8-hydroxydeoxyguanosine (8-OHdG), and the urinary albumin-to
      creatinine ratios (ACR) were determined before and after 16-week treatment.
      Neither metabolic parameters nor blood pressure levels differed between the two
      groups not only at baseline but also after the treatment. However, significant
      decreases in MCP-1, IL-6, hsCRP, TNF(alpha), 8-epi-PGF(2alpha), 8-OHdG and ACR
      levels, and a significant increase in the plasma adiponectin level were detected
      in the AZ group, but not in the NF group. The % change in the urinary oxidative
      stress markers correlated with that in ACR. Our results indicate that, in
      hypertensive patients with diabetic nephropathy, a combination therapy of RAS
      inhibitors and AZ is an effective therapeutic modality for decreasing not only
      blood pressure but also inflammations and oxidative stresses.

PMID- 18716363
TI  - Effects of cardiac energy efficiency in diastolic heart failure: assessment with
      positron emission tomography with 11C-acetate.
AB  - Diastolic heart failure (DHF) has become a high social burden, and its major
      underlying cardiovascular disease is hypertensive heart disease. However, the
      pathogenesis of DHF remains to be clarified. This study aimed to assess the
      effects of cardiac energy efficiency in DHF patients. (11)C-Acetate positron
      emission tomography and echocardiography were conducted in 11 DHF Japanese
      patients and 10 normal volunteers. The myocardial clearance rate of radiolabeled
      (11)C-acetate was measured to calculate the work metabolic index (WMI), an index
      of cardiac efficiency. The ratio of peak mitral E wave velocity to peak early
      diastolic septal myocardial velocity (E/e') was calculated to assess left
      ventricular (LV) filling pressure. The LV mass index was greater and the mean age
      was higher in the DHF patients than in the normal volunteers. There was no
      difference in WMI between the two groups. However, WMI varied widely among the
      DHF patients and was inversely correlated with E/e' (r=-0.699, p=0.017). In
      contrast, there was no correlation in the normal volunteers. In conclusion, the
      inefficiency of energy utilization is not a primary cause of diastolic
      dysfunction or DHF, and cardiac efficiency may not affect diastolic function in
      normal hearts. However, the energy-wasting state may induce the elevation of LV
      filling pressure in DHF patients, which was considered to principally result from
      the progressive diastolic dysfunction.

PMID- 18716364
TI  - Serum osteoprotegerin as a screening tool for coronary artery calcification score
      in diabetic pre-dialysis patients.
AB  - Although cardiovascular disease is a principal cause of death in patients with
      chronic kidney disease (CKD), it is often asymptomatic in diabetic patients. The
      coronary artery calcification score (CACS) measured by multidetector computed
      tomography (MDCT) is useful for screening ischemic heart disease in the general
      population. We investigated which clinical parameters predict high CACS in
      predialysis diabetic nephropathy (DN). Participants were 85 patients with DN.
      Nobody had any history of coronary angioplasty or coronary bypass surgery. We
      measured blood counts, blood chemistry, bone alkaline phosphatase, intact-PTH,
      interleukin-6, osteoprotegerin (OPG), hemoglobin A1c, 25-hydroxyvitamin D
      (25(OH)D) and fetuin-A. CACS and bone mineral density (BMD) were measured by a
      single 16-slice MDCT and DEXA, respectively. The median value of CACS equaled 256
      Agatston units (range 0-4494 units). Stepwise increase in CACS with CKD stage
      progression was observed (p<0.01 for trend). Simple regression analyses showed
      that Log (CACS+1) was positively correlated with age, systolic blood pressure,
      phosphorus and OPG. In addition, it was negatively correlated with nutritional
      parameters, such as body mass index, albumin, total-cholesterol and 25(OH)D.
      Fetuin-A and BMD had no impact on CACS. Multiple regression analyses showed that
      low albumin and high OPG were associated with high CACS. The sensitivity of OPG
      for detecting CACS>200 was 80%, when the cut-off value was 1.2 ng/mL. In
      conclusion, CACS increased with CKD stage progression in predialysis DN patients.
      Serum OPG was positively associated with high CACS and can be a useful screening
      tool for severe coronary calcification, whereas no association between fetuin-A
      and CACS was found.

PMID- 18716365
TI  - Impact of renin-angiotensin system inhibition on microalbuminuria in type 2
      diabetes: a post hoc analysis of the Shiga Microalbuminuria Reduction Trial
      (SMART).
AB  - The Shiga Microalbuminuria Reduction Trial (SMART) showed the advantage of ARB
      over CCB beyond the blood pressure (BP)-lowering effect in reducing
      microalbuminuria. To further assess the impact of BP control or renin-angiotensin
      system inhibition on microalbuminuria, the SMART patients were re-analyzed.
      Hypertensive patients with type 2 diabetes and microalbuminuria were randomly
      assigned to valsartan or amlodipine treatment groups for 24 weeks. Target blood
      pressure was set at <130/80 mmHg. Changes in the urinary albumin creatinine ratio
      (ACR) from baseline were assessed in the valsartan monotherapy (VM) group (n=33),
      the amlodipine monotherapy (AM) group (n=36), the concomitant valsartan and
      angiotensin-converting enzyme inhibitor group (VA) (n=33), and the concomitant
      amlodipine and angiotensin-converting enzyme inhibitor (AA) group (n=38). At the
      end of the study, mean BP was not different among the four treatment groups. The
      changes in ACR from baseline to the end of the treatment period in VM, AM, VA,
      and AA were -36%, +30%, -26%, and +8%, respectively. The dissociation between the
      anti-albuminuric and antihypertensive effects of valsartan or amlodipine was
      observed in the respective monotherapy groups. In the AA group, however, a
      significant positive relationship was found between the changes in ACR and those
      in systolic BP. In conclusion, RAS inhibitors may be necessary in order for
      calcium channel blockers to have an effect on microalbuminuria. Therefore, RAS
      inhibitors are first-line drugs for hypertensive patients with type 2 diabetes
      and microalbuminuria.

PMID- 18716366
TI  - Upper arm circumference is an independent predictor of left ventricular
      concentric hypertrophy in hypertensive women.
AB  - Upper arm circumference (UAC) measurement is necessary for the proper sizing of
      cuffs and is recommended for accurate blood pressure (BP) assessment. The aim of
      this report is to identify and quantify the relationships between UAC and the
      usual anthropometric measurements of body fat distribution and cardiac structure
      in hypertensive subjects. We evaluated 339 patients (202 women and 137 men) by
      medical history, physical examination, anthropometry, metabolic and inflammatory
      parameters, and echocardiography. Partial correlation analyses adjusted for age
      and body mass index revealed that anthropometric variables were significantly
      associated with echocardiographic parameters exclusively in women. In this
      regard, UAC correlated with interventricular septum thickness, posterior wall
      thickness, and relative wall thickness >or=0.45, while waist circumference was
      related to left cardiac chamber diameter. Multivariate analyses including age,
      body mass index, systolic BP, homeostasis model assessment index, and use of
      antihypertensive medications demonstrated that UAC was an independent predictor
      of left ventricular wall thickness and concentric hypertrophy in women. Further
      linear regression analyses revealed that waist circumference was an independent
      predictor of left ventricular end-diastolic and left atrial diameters in this
      gender. Overall, these findings suggest that UAC determination might serve not
      only as a routine approach preceding BP evaluation but also as a simple and
      feasible predictor of adverse LV remodeling in hypertensive women.

PMID- 18716367
TI  - Plasma level of asymmetric dimethylarginine (ADMA) as a predictor of carotid
      intima-media thickness progression: six-year prospective study using carotid
      ultrasonography.
AB  - This study was designed to determine the relationship between plasma asymmetric
      dimethylarginine (ADMA) and the development of carotid atherosclerosis. Cross
      sectional studies have revealed that plasma ADMA concentration is correlated with
      the intima-media thickness (IMT) of the carotid artery, but no prospective
      studies have appeared. Therefore we prospectively investigated whether or not
      plasma ADMA level can predict IMT progression. In a community-based cohort, we
      enrolled 712 subjects who were over 40 years old and who had no apparent
      cardiovascular diseases according to high-resolution carotid ultrasonography.
      Blood chemistries including ADMA were measured at baseline. In 575 subjects, IMT
      was re-measured 6 years later. The value of baseline ADMA for predicting IMT
      changes was investigated by multivariable analysis. At baseline, there was a
      significant (beta=0.321; p<0.001) relationship between IMT and ADMA levels.
      Multiple linear regression analysis revealed that baseline ADMA (beta=0.241;
      p<0.01) was the only predictor of IMT progression after adjustments for age, sex,
      baseline IMT, and four major risk factors (hypertension, hypercholesterolemia,
      diabetes mellitus, and smoking) plus hyperuricacidemia. Plasma ADMA was a
      predictor of carotid IMT progression.

PMID- 18716368
TI  - Relationship between carotid atherosclerosis and lumbar spine bone mineral
      density in postmenopausal women.
AB  - Osteoporosis and increased carotid intima-media thickness (IMT) have been
      associated with atherosclerosis. We investigated the correlation between carotid
      IMT and lumbar spine bone mineral density (BMD) in postmenopausal women. We
      studied the carotid IMT in 175 postmenopausal women, including 43 women (control)
      with normal spinal BMD, 73 women with osteopenia, and 59 women with osteoporosis.
      Carotid IMT was assessed by ultrasonography. BMD at the lumbar spine (lumbar 2 to
      4 vertebrae) was measured by dual-energy X-ray absorptiometry. Age, years since
      menopause, and carotid IMT were significantly greater in the osteoporosis group
      than in the control (all p<0.01) and osteopenia groups (all p<0.01). Estradiol
      was significantly lower in the osteoporosis group than in the control group
      (p<0.05). BMD was significantly lower in the osteoporosis group than in the
      osteopenia or control group (both p<0.01) and in the osteopenia group than in the
      control group (p<0.01). After adjusting for age, years since menopause, and
      estradiol, women with osteoporosis had significantly greater carotid IMT than
      controls (p<0.05). The univariate linear regression analysis revealed that
      carotid IMT was significantly positively correlated with age, years since
      menopause, and low-density lipoprotein (LDL) cholesterol (all p<0.05) and was
      significantly negatively correlated with estradiol and BMD (all p<0.05), but
      showed no significant association with other clinical variables. In multivariate
      regression analysis, the carotid IMT was significantly positively correlated with
      LDL cholesterol (p<0.01) and negatively correlated with BMD (p<0.01), but not
      with other variables. Carotid atherosclerosis might be associated with lumbar
      spine bone mass in postmenopausal women, suggesting that postmenopausal women
      with osteoporosis may have more advanced carotid atherosclerosis than those with
      a normal bone mass.

PMID- 18716369
TI  - Combined effects of an 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor
      and angiotensin II receptor antagonist on nitric oxide bioavailability and
      atherosclerotic change in myocardial infarction-prone Watanabe heritable
      hyperlipidemic rabbits.
AB  - We investigated the effects of co-administration of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor and angiotensin II type 1 receptor
      blocker (ARB) on nitric oxide (NO) bioavailability in genetically hyperlipidemic
      rabbits with our newly developed NO sensor. A total of 36 myocardial infarction
      prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits equally derived (n=6 per
      group) were treated with 1) vehicle (control), 2) hydralazine (15 mg/kg/d), 3)
      the HMG-CoA reductase inhibitor pitavastatin (P: 0.5 mg/kg/d), 4) the ARB
      valsartan (V: 5 mg/kg/d), and 5) pitavastatin+valsartan (P+V) together without or
      6) with N(G)-nitro-L-arginine methyl ester (L-NAME) for 8 weeks. After treatment,
      acetylcholine (ACh)-induced NO production was measured as a surrogate for
      endothelium protective function, and vascular peroxynitrite (a product of
      superoxide and NO) was measured for assessing dysfunctional endothelial NO
      synthase activity. Plaque area was quantified by histology as well as optical
      coherence tomography (OCT). Intra-aortic infusion of ACh produced an increase in
      plasma NO concentration, which was significantly greater with all drug treatments
      than with the control. P+V increased ACh-induced NO by 4.1 nmol/L significantly
      more than either P or V singly. The vascular peroxynitrite concentration was 1.6
      pmol/mg protein in the control group and significantly less than those in the P-
      and V-monotherapy-groups. The lowest peroxynitrite concentration was observed in
      the P+V group (0.4 pmol/mg protein), which was significantly lower than those in
      the P- and the V-monotherapy-groups. OCT and histology of the thoracic aorta
      revealed that the plaque area decreased significantly more with the combination
      than with the monotherapy. In conclusion, the combined treatment with an HMG-CoA
      reductase inhibitor and an ARB may have additive protective effects on
      endothelial function as well as atherosclerotic change.

PMID- 18716370
TI  - Defective phosphatidylinositol 3-kinase signaling in central control of
      cardiovascular effects in the nucleus tractus solitarii of spontaneously
      hypertensive rats.
AB  - Recently we have shown functional involvement of the phosphatidylinositol 3
      kinase (PI3K)-Akt-nitric oxide synthase (NOS) signaling pathway in central
      control of cardiovascular effects in the nucleus tractus solitarii (NTS) of
      normotensive Wistar-Kyoto (WKY) rats. In this study we determined whether
      PI3K/Akt signaling was defective in spontaneously hypertensive rats (SHR). WKY
      rats and SHR were anesthetized with urethane. Mean blood pressure (MBP) and heart
      rate (HR) were monitored intra-arterially. Unilateral microinjection (60 nL) of
      insulin (100 IU/mL) into the NTS produced prominent depressor and bradycardic
      effects in 8- and 16-week-old normotensive WKY and 8-week-old SHR. However, no
      significant cardiovascular effects were found in 16-week-old SHR after insulin
      injection. Furthermore, pretreatment with PI3K inhibitor LY294002 and NOS
      inhibitor L-NAME into the NTS attenuated the cardiovascular response evoked by
      insulin in WKY and 8-week-old SHR but not in 16-week-old SHR. Unilateral
      microinjection of 1 mmol/L of PI(3,4,5)P(3) (phosphatidylinositol 3,4,5
      triphosphate), a phospholipids second messenger produced by PI3K, into the NTS
      produced prominent depressor and bradycardic effects in 8- or 16-week-old WKY
      rats as well as 8-week-old SHR but not in 16-week-old SHR. Western blot analysis
      showed no significant increase in Akt phosphorylation in 8-week-old pre
      hypertensive SHR after insulin injection. Similar results were also found in
      hypertensive 16-week-old SHR. Our results indicate that the Akt-independent
      signaling pathway is involved in NOS activation to regulate cardiovascular
      effects in the NTS of 8-week-old pre-hypertensive SHR. Both Akt-dependent and Akt
      independent signaling pathways are defective in hypertensive 16-week-old SHR.

PMID- 18716371
TI  - Effects of obesity and smoking on mental stress-induced blood pressure and
      augmentation index responses in normotensive young males: the J-SHIPP study.
AB  - Exaggerated blood pressure (BP) response to mental stress has been known to be a
      prognostic factor for cardiovascular disease. It has been argued that such
      unusual vascular reactivity to mental stress may arise from insulin resistance.
      To examine the vascular responses to mental stress, we evaluated the stress
      related changes in BP and the augmentation index (AI), an index of arterial
      stiffness, in normotensive young males. Changes in late systolic BP (SBP2)
      representing central aortic pressure were also examined. Subjects were 86 males
      (21+/-2 years), 13 of whom were classified as obese (>or=25 kg/m(2)). AI was
      obtained from the radial arterial waveform as a ratio of the height of the late
      systolic peak to that of the first peak. Blood pressure and AI measurements were
      taken before, during and after a simple mental arithmetic test (MAT) lasting 3
      min. Systolic BP (baseline 125+/-13, during MAT 133+/-13, post-MAT 124+/-11 mmHg;
      p<0.001) and heart rate (74+/-12, 81+/-13, 74+/-11 beats/min; p<0.001) were
      significantly increased during the MAT, whereas AI showed a slight reduction. In
      a separate analysis, the opposite response was observed between obese subjects
      showing increased AI (54+/-11, 56+/-13, 52+/-11%) and non-obese subjects who
      showed reduced AI (54+/-12, 51+/-12, 53+/-12%; p=0.032). The responses in SBP and
      SBP2 (obese 103+/-14, 117+/-12, 104+/-12; non-obese 98+/-13, 104+/-12, 97+/-12
      mmHg; p=0.007) were also larger in the obese subjects. Stress-related transient
      increases in arterial stiffness may be involved in the exaggerated responses in
      aortic pressure in obese subjects.

PMID- 18716372
TI  - Effects of early and late chronic pressure overload on extracellular matrix
      remodeling.
AB  - The left ventricle (LV) remodels with age and in response to pressure overload.
      While aging and pressure overload are superimposed in the clinical context, the
      structural and functional consequences of the individual processes are not well
      understood. Accordingly, the objective of this study was to compare the effects
      of both early and late chronic hypertension on extracellular matrix (ECM)
      remodeling. The following groups of Dahl rats were studied: 1) young salt
      resistant (control, n=6); 2) young salt-sensitive (early phase of chronic
      hypertension, n=6); 3) middle-aged salt-resistant (aging, n=5); and 4) middle
      aged salt-sensitive (late phase of chronic hypertension, n=6). We measured LV
      mass (LVM) and body weight (BW) and immunoblotted a panel of matrix
      metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and
      ECM proteins. Total collagen increased, several MMPs decreased, and TIMP-1
      increased in the early phase of hypertension, consistent with fibrosis. Active
      MMP-8 decreased from 8,010+/-81 U in young salt-resistant to 5,260+/-313 U in
      young salt-sensitive (p<0.05) rats. During the late phase, chronic hypertension
      decreased total collagen levels and increased MMP-8 and MMP-14 (all p<0.05).
      Based on good-fit modeling analysis, MMP-14 (45 kDa) correlated positively with
      changes in LVM/BW during the early phase. In conclusion, this is the first study
      to evaluate MMP levels during both early and late chronic phases of hypertension.
      Our results highlight that ECM remodeling in response to pressure overload is a
      dynamic process involving excessive ECM accumulation and degradation.

PMID- 18716373
TI  - Angiotensin II-stimulated collagen synthesis in aortic adventitial fibroblasts is
      mediated by connective tissue growth factor.
AB  - Angiotensin II (Ang II), a potent mediator of vascular remodeling, can stimulate
      the synthesis of extracellular matrix in vascular cells. Recent studies indicate
      that connective tissue growth factor (CTGF) is involved in collagen synthesis.
      There is also increasing evidence that adventitial fibroblasts (AFs) are actively
      involved in vascular remodeling. However, whether collagen synthesis by AFs is
      mediated by CTGF, or whether it is relevant to Ang II, has not been studied. The
      present study was conducted to determine whether CTGF is expressed in AFs, and if
      so, whether the CTGF produced by AFs participates in collagen synthesis. The AFs
      were isolated from thoracic aorta of Wistar-Kyoto rats (WKY). The expression of
      CTGF was measured by Western blot or real-time PCR. Collagen synthesis was
      assessed by [(3)H]proline incorporation. Our results suggested that CTGF was
      expressed in AFs and secreted into medium. Ang II increased CTGF mRNA and protein
      expression in a time- and dose-dependent manner, with the maximal protein
      increase occurring at 24 h with an Ang II dose of 10(-7) mol/L, and this increase
      was inhibited by the Ang II receptor type 1 (AT(1)-R) antagonist losartan, but
      not by the Ang II receptor type 2 (AT(2)-R) antagonist PD123319. Ang II dose
      dependently stimulated the incorporation of [(3)H]proline into cultured AFs, and
      this effect was inhibited by a CTGF antisense oligodeoxynucleotide.
      Overexpression of CTGF by pcDNA3.1(+)/CTGF increased [(3)H]proline incorporation
      in cultured AFs. The results demonstrated that, in cultured AFs, Ang II increased
      CTGF production via AT(1)-R, which could be mediators of collagen synthesis by
      Ang II. This finding suggests that CTGF might be a novel target for antifibrotic
      therapy in vascular diseases.

PMID- 18716374
TI  - Role of the angiotensin II type 2 receptor in arterial remodeling after wire
      injury in mice.
AB  - The angiotensin II type 2 (AT2) receptor promotes apoptosis and inhibits cell
      proliferation. In the present study, we investigated the role of the AT2 receptor
      in vascular repair and remodeling following severe vascular injury using AT2
      knockout (AT2KO) mice. Left femoral arteries of AT2KO mice and wild-type (WT)
      control mice were injured by a 0.38 mm steel wire inserted from the lumen. Twenty
      eight days after the injury, a concentric vascular wall thickening, composed
      largely of neointima, was noted both in AT2KO and WT mice. The area occupied by
      the neointima and the cell count within it were not different in the two mouse
      strains. However, the area of the medial layer and the cell count within it were
      significantly larger in AT2KO mice than in WT mice. A BrdU incorporation assay
      showed that the proliferative activity was high in the neointima but it was not
      different between the strains. On the other hand, apoptosis assessed by terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) was
      significantly inhibited in the neointima and the media of AT2KO mice compared to
      the levels in WT mice. However, the number of TUNEL-positive cell was much
      smaller in the neointima than in the medial layer in both strains. Taken
      together, these results indicate that AT2 receptors promote the apoptosis of
      vascular cells but have no net effect on the neointimal cell growth or luminal
      narrowing after wire injury. The AT2 receptor may be involved in the control of
      medial layer thickness, at least in part, through medial cell apoptosis.

PMID- 18716375
TI  - The specific mineralocorticoid receptor blocker eplerenone attenuates left
      ventricular remodeling in mice lacking the gene encoding guanylyl cyclase-A.
AB  - Mineralocorticoid receptor (MR) blockers attenuate cardiac remodeling in
      experimental models of heart failure, myocardial infarction and pressure
      overload, in which the renin-angiotensin-aldosterone system is activated. Mice
      lacking the gene encoding guanylyl cyclase-A (GC-A), a common receptor for atrial
      and brain natriuretic peptide (ANP and BNP, respectively), show marked cardiac
      hypertrophy and fibrosis, which are almost completely inhibited by both genetic
      and pharmacological blockade of type 1 angiotensin II receptors. However, the
      effect of eplerenone, a specific MR blocker, on cardiac remodeling in GC-A
      knockout (GC-A KO) mice remains unknown. Male 12-week-old GC-A KO mice were
      assigned to control, eplerenone and hydralazine groups (n=6-7/group). Treatment
      with eplerenone at a dose of 100 mg/kg body weight/d reduced heart weight/body
      weight ratios, interstitial fibrosis and blood pressure to levels similar to
      those seen in wild type mice, in association with reduced transcription of atrial
      natriuretic peptide, brain natriuretic peptide, transforming growth factor-beta1,
      collagen I and collagen III. Although hydralazine (5 mg/kg body weight/d) exerted
      a similar effect on blood pressure, it did not inhibit the cardiac remodeling in
      GC-A KO mice. In conclusion, eplerenone attenuates cardiac remodeling in GC-A KO
      mice, most likely in a blood pressure-independent manner, which suggests that
      signaling downstream of MR is involved in the ventricular remodeling of GC-A KO
      mice.

PMID- 18716376
TI  - Angiotensin II increases expression of IP-10 and the renin-angiotensin system in
      endothelial cells.
AB  - Angiotensin II promotes vascular inflammation, which plays important roles in
      vascular injury. In this study, we found that angiotensin II-stimulated human
      endothelial cells increased the release of a CXC chemokine, IP-10, according to
      an antibody array. IP-10 expression was higher in the endothelium of coronary
      blood vessels in mice infused with angiotensin II than in control. Quantitative
      real-time PCR analysis revealed that angiotensin II significantly increased IP-10
      mRNA expression compared to control. Pretreatment with valsartan, but not with
      PD123319, blocked angiotensin II-induced IP-10 mRNA expression. IP-10 levels in
      conditioned media detected by ELISA increased in response to angiotensin II
      compared to control, which was blocked by the pretreatment with valsartan. These
      data indicate that angiotensin II stimulates IP-10 production from endothelial
      cells via angiotensin II type 1 receptors. In endothelial cells, IP-10
      significantly increased mRNA expression of renin, angiotensin-converting enzyme,
      and angiotensinogen. IP-10 also increased angiotensin II levels in conditioned
      media compared to control. Angiotensin II significantly increased mRNA expression
      of renin, angiotensin converting enzyme and angiotensinogen, which was blocked by
      neutralization of IP-10 with antibody in endothelial cells. IP-10 neutralization
      with antibody blocked angiotensin II-induced apoptosis and cell senescence in
      endothelial cells. These data indicate that IP-10 is involved not only in
      leukocyte-endothelial interaction but also in the circuit of endothelial renin
      angiotensin system activation that potentially promotes atherosclerosis.

PMID- 18716377
TI  - Global qualitative risk management (control banding) activities.

PMID- 18716378
TI  - Interethnic variability of plasma paraoxonase (PON1) activity towards
      organophosphates and PON1 polymorphisms among Asian populations--a short review.
AB  - Organophosphate (OP) poisoning is a progressively worrying phenomenon as
      worldwide pesticide production and consumption has doubled. On average, WHO
      estimates that 3% of agricultural workers in developing Asian countries suffer an
      episode of pesticide poisoning every year. Furthermore, the threat of OP usage in
      terrorism is existent, as seen by the subway tragedy in Tokyo in 1995 where sarin
      was used. Despite these alarming facts, there is currently no global system to
      track poisonings related to pesticide use. Human serum paraoxonase (PON1) is the
      enzyme that hydrolyses OP compounds. Serum PON1 levels and activity vary widely
      among different ethnic populations. Two commonly studied polymorphisms of PON1
      are PON1Q192R and PON1L55M. PON1R192 hydrolyses paraoxon faster than PON1Q192 but
      hydrolyses diazoxon, sarin and soman eight times slower, and vice versa. PON1M55
      has lower plasma levels of PON1 than PON1L55. As the prevalence of the different
      alleles and genotypic distribution vary between the Asian populations we studied,
      we propose the necessity to study PON1 polymorphisms and its role in OP toxicity
      in Asian populations. This would help safeguard the proper care of agricultural
      workers who might be affected by OP poisoning, and alert relevant anti biological
      terrorism agencies on possible risks involved in the event of an OP attack and
      provide effective counter measures.

PMID- 18716379
TI  - Limited validity of o-cresol and benzylmercapturic acid in urine as biomarkers of
      occupational exposure to toluene at low levels.
AB  - This study was initiated to evaluate o-cresol and benzylmercapturic acid in urine
      in comparison with other biomarkers, as tools to estimate the intensity of
      occupational exposure to toluene at low levels. In total, 108 solvent exposed
      workers (engaged in tape production) and 17 non-exposed controls (all men)
      participated in the study. The surveys were conducted in the second half of
      working weeks. Diffusive sampling was conducted to measure 8-h time-weighted
      average intensity of occupational exposure to toluene. Blood and urine samples
      were collected at the end of a working shift. Blood samples were subjected to
      analysis for toluene (Tol-B), and urine samples were analyzed for benzyl alcohol
      (BeOH-U), benzylmercapturic acid (BMA-U), o-cresol (o-CR-U), hippuric acid (HA-U)
      and toluene (Tol-U) by the methods previously described. The toluene
      concentrations in workplaces were low in general, with a geometric mean (GM) and
      the maximum concentration of 1.9 ppm and 8.8 ppm, respectively. The statistical
      analyses of the six biomarkers for correlation with air-borne toluene showed that
      both Tol-B and Tol-U gave a high correlation coefficient of 0.58 to 0.61
      (p<0.01), whereas the coefficients for BeOH-U and BMA-U together with HA-U were
      all low (up to 0.22, depending on the correction for urine density) and
      statistically insignificant (p>0.10) in most cases. o-CR-U had an intermediary
      coefficient of 0.20 (p<0.05). Comparison with previous publications disclosed
      that BeOH-U, BMA-U and HA-U correlate with toluene in air when the exposure is
      intense (e.g., 50 ppm or above), but no longer proportional to air-borne toluene
      when the exposure is low, e.g., 2 ppm. Such appeared to be also the case for o-CR
      U. In over-all evaluation, the validity of o-CR-U in monitoring occupational
      exposure to toluene at low levels (e.g., 2 ppm) appear to be limited, and BMA-U
      is not an appropriate biomarker. BeOH-U and HA-U are also inappropriate for this
      purpose. Only Tol-B and Tol-U may be employed to estimate toluene exposure at low
      levels.

PMID- 18716380
TI  - Relationship of nurse burnout with personality characteristics and coping
      behaviors.
AB  - Burnout of nurses at university hospitals was analyzed in relation to their
      personality characteristics and coping behaviors. A self-administered
      questionnaire regarding burnout (the Copenhagen Burnout Inventory), work-related
      stressors (the Nursing Job Stressor Scale), personality characteristics (Short
      Form Eysenck Personality Questionnaire-Revised), and coping behaviors (the short
      Japanese version of Brief COPE) was used. We obtained answers from 778 nurses
      (response rate: 94.9%), and analyzed 707 female registered nurses. Multiple
      regression analysis showed that neuroticism was more closely related to personal,
      work-related, and client-related burnout than extroversion. Covariate structure
      analysis revealed that among the nurses with high neuroticism and low
      extroversion, client-related burnout was found to be correlated with stressors in
      relation to conflict with patients and with positive coping behaviors. Among the
      nurses with low neuroticism and high extroversion, client-related burnout
      correlated with the coping behavior of behavioral disengagement and conflict with
      patients. In both groups, an increase in quantitative workload was associated
      with a higher score for stressors arising from conflict with patients, leading to
      client-related burnout. These results suggest that acquisition of skills to
      cultivate appropriate coping behaviors might be useful for reducing client
      related burnout in relation to nurses' personality characteristics. These
      findings need to be further endorsed by intervention studies.

PMID- 18716381
TI  - Acupuncture can reduce perceived pain, mood disturbances and medical expenses
      related to low back pain among factory employees.
AB  - To investigate the effects of acupuncture on perceived pain, mood disturbances
      and medical expenses related to low back pain (LBP), an intervention study was
      performed among 72 employees of a steel company, 70 males and 2 females, aged
      53.1+/-7.1 (mean+/-SD) yr, with LBP. They received acupuncture treatment once a
      week for 8 wk (from October to December 1998) by licensed acupuncturists,
      adopting a new hypothesis of the Meridian test. Perceived pain scale, and Profile
      of Mood States (POMS) were administered. Past and present histories of employees'
      visits to hospitals and their medical expenses for LBP were surveyed from
      receipts obtained from the subjects' branch factory and from receipts from
      another nearby branch factory (control) during the period from April 1998 to
      March 1999. After 8 wk of treatment, patients with LBP reported diminished pain
      (p<0.01). POMS showed a significant decrease in the total mood disturbance score
      (p<0.001). The number of visits to conventional hospitals (12.1+/-8.0 vs. 0.8+/
      0.8 per month, p<0.05) and standardized medical expenses for LBP (100.1+/-89.6
      vs. 7.3+/-6.9 per month, p<0.05) after acupuncture intervention (November 1998 to
      March 1999) were significantly decreased as compared with those before
      intervention (April 1998 to October 1998). In contrast, such decreases were not
      observed in employees from the control branch factory. It is suggested that
      acupuncture can reduce medical expenses for LBP through improvement in mood and
      pain.

PMID- 18716382
TI  - Having more healthy practice was associated with low white blood cell counts in
      middle-aged Japanese male and female workers.
AB  - White blood cell (WBC) count is well known to be an independent risk marker for
      cardiovascular disease. The aim of this study is to examine the relationships of
      WBC counts to seven health practices including obesity, eating habits, smoking,
      alcohol intake, sleeping, physical activity, and perceived mental stress, and
      then clustering the relevant healthy practices. The subjects were 1,492 male and
      316 female Japanese workers aged 40 yr and over in 2002. Each of seven health
      practices from a self-administered questionnaire was categorized as a 'healthy'
      or 'unhealthy' practice, and WBC counts from fasting blood samples were
      determined by automated particle counters. The means of age and WBC counts were
      49.5 yr and 5,375 cells/microl in men, and 48.6 yr and 4,890 cells/microl in
      women, respectively. After multivariate adjustments for all health practices and
      age, the estimated WBC counts were significantly lower in normal weight subjects
      and never or former smokers (p<0.01). Age-adjusted WBC counts decreased
      significantly by 204.9+/-23.7 cells/microl (means+/-SE) and 117.6+/-53.2
      cells/microl for each increase in one healthy practice (p<0.05), respectively,
      suggesting that cultivating healthier practices would lead to lower WBC counts.
      This study recommends modifying unhealthy practice one by one and maintaining
      healthy practices as an effective strategy for the prevention of atherosclerotic
      diseases, in addition, to quit smoking or abstain from heavy smoking especially
      in men is important to prevent the low-grade inflammation.

PMID- 18716383
TI  - Alteration of brain levels of neurotransmitters and amino acids in male F344 rats
      induced by three-week repeated inhalation exposure to 1-bromopropane.
AB  - The present study investigated the effects of 1-bromopropane (1BP) on brain
      neuroactive substances of rats to determine the extent of its toxicity to the
      central nervous system (CNS). We measured the changes in neurotransmitters
      (acetylcholine, catecholamine, serotonin and amino acids) and their metabolites
      or precursors in eight brain regions after inhalation exposure to 1BP at 50 to
      1,000 ppm for 8 h per day for 7 d per week for 3 wk. Rats were sacrificed at 2 h
      (Case 1), or at 19 h (Case 2) after the end of exposure. In Case 1, the level of
      5-hydroxyindoleacetic acid (5HIAA) was lowered in some brain regions by 1BP
      exposure. The decrease of 5HIAA in the frontal cortex was statistically
      significant at 50 ppm 1BP exposure. In Case 2, gamma-amino butyric acid (GABA)
      and taurine were decreased in many brain regions of exposed rats, and a
      significant decrease of taurine in the midbrain occurred at 50 ppm 1BP exposure.
      In both cases of 2-h and 19-h intervals from the end of exposure to sacrifice,
      aspartate and glutamine levels were elevated in many brain regions, but the
      acetylcholine level did not change in any brain region. Three-week repeated
      exposure to 1BP produced significantly changes in amino acid contents of rat
      brains, particularly at 1,000 ppm.

PMID- 18716384
TI  - Effects of heating appliances with different energy efficiencies on associations
      among work environments, physiological responses, and subjective evaluation of
      workload.
AB  - To clarify the association between heat stress, physiological responses and
      subjective workload evaluations in kitchens using an induction heating stove (IH
      stove) or gas stove. The study design was an experimental trial involving 12
      young men. The trial measured ambient dry-bulb temperature, globe temperature,
      wet-bulb globe temperature (WBGT) and relative humidity; the subjects' weight,
      heart rate, blood pressure, oxygen uptake, amount of activity, body temperature,
      subjective awareness of heat and workload before and after mock cooking for 30
      min. The IH stove insignificantly increased heat indicators in the work
      environment and workers showed lower oxygen uptake, skin temperature, subjective
      awareness of heat and workload after heat exposure. Both physiological load and
      subjective awareness of heat and workload were slight in kitchens using the IH
      stove, which provided a better work environment.

PMID- 18716385
TI  - Self-reported occupational health issues among Lithuanian dentists.
AB  - This article describes the second phase of a large study of Lithuanian dentists'
      health, and focuses on self-reported physical health complaints, general health
      state and associations between the two. In 2006, a postal questionnaire survey of
      all (N=2,449) licensed dentists registered with the Lithuanian Dental Association
      was conducted, obtaining a response rate of 68.2%. Fatigue (94.7%) and back pain
      (91.0%) were the most prevalent physical complaints reported, and they were also
      the most likely to become chronic among all physical disorders. Hypertension,
      joint diseases and allergy were the most prevalent diagnosed and treated diseases
      during the previous 12 months. Only half of the surveyed Lithuanian dentists
      (50.4%) rated their health as satisfactory. Logistic regression revealed that
      fatigue (Odds Ratio: 0.52; 95%CI: 0.29-0.94), headache (OR: 0.62; 95%CI: 0.42
      0.90), hand problems (OR: 0.62; 95%CI: 0.44-0.87), chest pain (OR: 0.51; 95%CI:
      0.40-0.64) and musculoskeletal complaints (OR: 0.41; 95%CI: 0.28-0.60) had a
      significant negative impact on dentists' self-reported general health. Overall,
      this study suggests that Lithuanian dentists do experience a certain amount of
      occupationally-related health problems. It is therefore important to increase
      health knowledge on occupational hazards and also to emphasize the importance of
      early diagnosis and treatment for these disorders in Lithuania, as elsewhere.

PMID- 18716386
TI  - Construction equipment and motor vehicle related injuries on construction sites
      in Turkey.
AB  - Research on occupational accidents on construction sites in Turkey is very few.
      Moreover, research on motor vehicle and equipment accidents also do not exist.
      Investigation in the scope of this study shows that after falls and contact with
      electricity, accidents involving heavy equipment and motor vehicles rank third
      and fourth, respectively. This study aims to reveal the characteristics of these
      types of accidents, deduct the prominent causes that lead to fatalities as well
      as permanent disabilities using the present data. With the aid of obtained
      results, recommendations are made for safety experts on how to derive data from
      insufficient sources in Turkey and to evaluate these data for prevention and
      mitigation of the risks that construction workers are exposed to. 168 fatal and
      38 non-fatal traffic accident-caused incidents as well as 206 fatal and 97 non
      fatal construction equipment accidents, which were selected from official
      statistics and expert reports, were taken into consideration. Analysis and
      classification of these accidents were done according to the way they happened,
      the type of construction site and the occupation of the victims. Moreover, the
      leading causes of fatal and non-fatal injuries, to which drivers, operators and
      co-operators are exposed, are presented. Critical findings concerning prominent
      ways of occurrence, type of construction work and occupation are presented; and a
      number of measures for reducing the present risks are suggested. Some approaches
      for analysing relevant data are proposed for further research.

PMID- 18716387
TI  - Blood vitamin C levels of motorized tricycle drivers in Paranaque, Philippines.
AB  - Vitamin C is an essential micronutrient maintaining the state of well being of
      individuals. This study examined factors affecting and the blood vitamin C levels
      of motorized tricycle drivers in Paranaque City, Philippines. Consenting drivers
      (N=49) were included in the study and were assessed through self-administered
      questionnaires, 24-h food recalls, and anthropometric measurements and on the
      analysis of their blood vitamin C levels. Factors related to the blood vitamin C
      levels of the motorized tricycle drivers were determined by correlation analysis.
      Majority (79.6%) of drivers had low blood vitamin C levels. Workplace and vitamin
      C supplementations (p<0.05) were significantly related to the blood vitamin C
      levels of the motorized tricycle drivers. Further studies are recommended to
      understand the problem and the determinants of vitamin C deficiency among the
      general population.

PMID- 18716388
TI  - A trail of individual education for hearing protection with an instrument that
      measures the noise attenuation effect of wearing earplugs.
AB  - The aim of this study was to investigate the effect of individual training of
      workers, using an instrument to quantitatively evaluate the noise attenuation
      gained with the use of earplugs, on the efforts to promote the use of hearing
      protection devices. The subjects were 68 male workers exposed to noise of above
      80 dBA at an electronic parts manufacturer in Japan. They received group
      instruction on the prevention of noise-induced hearing loss, and individual
      education on the effect of the proper use of earplugs. The individual education
      was done with the use of an instrument that measures the noise attenuation effect
      of wearing earplugs. After the training, the prevalence of the regular use of
      hearing protectors increased. Among workers in loud working environments, it
      increased from 46% to 66% over two months after the training. The percentage of
      workers who obtained a sufficient noise attenuation effect of>or=25 dB in both
      ears with the proper use of earplugs also increased, from 46% before the training
      to 72% immediately afterward. These effects were still observed about two months
      after the intervention. The results suggest that the present individual training
      may be an effective means to increase both the usage rate and the proper use of
      hearing protection devices, perhaps because it deepens individuals' understanding
      of the effect of the proper use of such devices.

PMID- 18716389
TI  - A survey for rhinitis in an automotive ring manufacturing plant.
AB  - We report findings regarding otolaryngologist-confirmed rhinitis, current
      exposure to MWF aerosols, fungi, and endotoxins for workers in a plant
      manufacturing automobile piston rings. Questionnaire data showed that 61.5% of
      187 workers exhibited rhinitis-related symptoms. Rhinitis was confirmed in 99 of
      115 workers whom were medically examined. Otolaryngologist-confirmed rhinitis was
      present in 10 of 19 grinding workers (52.6%), 67 of 142 production workers
      (47.2%), and 22 of 26 quality control (QC) workers (84.6%). These rates are much
      higher than the rates of rhinitis-related symptoms in automobile plants and other
      occupational settings and quite high even allowing for the common occurrence of
      rhinitis in the general population. We found that rhinitis could develop even in
      workers exposed to less than 0.5mg/m(3) MWF aerosol. The average exposure to
      fungi exceeded 10 x 10(3) CFU/m(3), a level higher than that reported for other
      automobile plants. Although we were unable to identify significant risk factors
      for rhinitis using only the physician-confirmed rhinitis cases, this study
      concludes that exposure to MWF aerosol, which would include microbes and metals,
      could contribute to a high occurrence of rhinitis in grinding and production
      workers. Forty-nine workers (63.6%) of 77 rhinitis patients in grinding and
      production operations were determined to handle synthetic MWF directly. For QC
      workers, for whom the prevalence of physician-confirmed rhinitis was highest,
      exposure to a low level of MWF aerosol, including specific microbe species we
      couldn't identify, bright light, dry air, and certain work characteristics during
      inspection are possible risk factors for development of rhinitis. Further studies
      including identification of fungi species should be conducted so a firm
      conclusion can be made regarding the development of rhinitis in QC manufacturing
      plant workers.

PMID- 18716390
TI  - Determination of exposure to respirable quartz in the stone crushing units at
      Azendarian-West of Iran.
AB  - The purpose of this study is to describe the personal exposure to respirable dust
      and quartz and in stone crushing units located at west of Iran. A size of 40
      personal samples and 40 stationary samples were obtained and analysis was done by
      X-ray diffraction (XRD). The results of personal sampling were shown the
      concentrations of respirable dust exposure level in workers of process, hopper
      and drivers were 1.90, 2.22, 1.41 times greater than Occupational Safety and
      Health Administration permissible exposure limit (OSHA PEL). The average value of
      total dust and respirable dust emission from stationary sources was 9.46 mg/m(3),
      1.24 mg/m(3) respectively, showing that 13.8 % of total dust is respirable. The
      efficiency of local exhaust ventilation (LEV) to control of particles inside of
      industrial units was greater than 99%. It is concluded from this research the
      particulate generated from stone crushing activities contain a significant amount
      of respirable particle. The amount of free silica in stone quartz is 85 to 97
      percent that emission of particles effect to health workers. LEV has important
      effect in the removal of silica particles in stone crushing units. The worker of
      hoppers still exposed to silica more than standard limits.

PMID- 18716391
TI  - The influence of the call with a mobile phone on heart rate variability
      parameters in healthy volunteers.
AB  - It is possible that electromagnetic field (EMF) generated by mobile phones (MP)
      may have an influence on the autonomic nervous system (ANS) and modulates the
      function of circulatory system. The aim of the study was to estimate the
      influence of the call with a mobile phone on heart rate variability (HRV) in
      young healthy people. The time and frequency domain HRV analyses were performed
      to assess the changes in sympathovagal balance in a group of 32 healthy students
      with normal electrocardiogram (ECG) and echocardiogram at rest. The frequency
      domain variables were computed: ultra low frequency (ULF) power, very low
      frequency (VLF) power, low frequency (LF) power, high frequency (HF) power and
      LF/HF ratio was determined. ECG Holter monitoring was recorded in standardized
      conditions: from 08:00 to 09:00 in the morning in a sitting position, within 20
      min periods: before the telephone call (period I), during the call with use of
      mobile phone (period II), and after the telephone call (period III). During 20
      min call with a mobile phone time domain parameters such as standard deviation of
      all normal sinus RR intervals (SDNN [ms]--period I: 73.94+/-25.02, period II:
      91.63+/-35.99, period III: 75.06+/-27.62; I-II: p<0.05, II-III: p<0.05) and
      standard deviation of the averaged normal sinus RR intervals for all 5-mm
      segments (SDANN [ms]--period I: 47.78+/-22.69, period II: 60.72+/-27.55, period
      III: 47.12+/-23.21; I-II: p<0.05, II-III: p<0.05) were significantly increased.
      As well as very low frequency (VLF [ms2]--period I: 456.62+/-214.13, period II:
      566.84+/-216.99, period III: 477.43+/-203.94; I-II: p<0.05), low frequency (LF
      [ms(2)]--period I: 607.97+/-201.33, period II: 758.28+/-307.90, period III:
      627.09+/-220.33; I-II: p<0.01, II-III: p<0.05) and high frequency (HF [ms(2)]-
      period I: 538.44+/-290.63, period II: 730.31+/-445.78, period III: 590.94+/
      301.64; I-II: p<0.05) components were the highest and the LF/HF ratio (period I:
      1.48+/-0.38, period II: 1.16+/-0.35, period III: 1.46+/-0.40; I-II: p<0.05, II
      III: p<0.05) was the lowest during a call with a mobile phone. The tone of the
      parasympathetic system measured indirectly by analysis of heart rate variability
      was increased while sympathetic tone was lowered during the call with use of a
      mobile phone. It was shown that the call with a mobile phone may change the
      autonomic balance in healthy subjects. Changes in heart rate variability during
      the call with a mobile phone could be affected by electromagnetic field but the
      influence of speaking cannot be excluded.

PMID- 18716392
TI  - Evaluation of an internet-based self-help program for better quality of sleep
      among Japanese workers: a randomized controlled trial.
AB  - The effectiveness of Internet-based self-help programs for insomnia is still
      unclear. A randomized controlled trial was conducted to evaluate the effect of an
      Internet-based self-help program for better quality of sleep among adult workers.
      Forty-three volunteers were recruited and randomly assigned to either an
      intervention group (n=21) or a waiting-list group (n=22). The intervention group
      participated in a two-week Internet-based program, including selecting and daily
      practicing sleep-related target behaviors and monitoring those behaviors along
      with sleep quality. At the same time, each participant received automatically
      generated, personalized messages and reports both daily and weekly. A total of 12
      intervention group participants and 18 waiting-list group participants completed
      questionnaires at baseline, post-intervention, and at a 3-wk follow-up.
      Subjective sleep quality was measured by a self-reported questionnaire developed
      for this study. The sleep quality score increased in the intervention group at
      post-intervention, with a significant interaction effect [F(1,28)=5.19, p=0.031].
      Sleep-related behaviors also greatly increased in the intervention group at post
      intervention, with a significant interaction effect [F(1,28)=7.14, p=0.012].
      Sleep-onset latency reduced in the intervention group at follow-up, with a
      marginally significant effect [F(1,28)=3.52, p=0.071]. The Internet-based self
      help program improves subjective sleep quality and sleep-onset latency among
      adult workers.

PMID- 18716393
TI  - Urinary mutagenicity in chemical laboratory workers exposed to solvents.
AB  - Solvents represent an important group of environmental pollutants to which people
      are exposed daily in the workplace. The physico chemical properties of solvents
      may result in disturbances to cellular structures, including damage to DNA.
      However, the effects of mixtures of solvents are not well known. Mutations caused
      by environmental agents are related to cancer development and other degenerative
      diseases. The work in a research laboratory that uses several types of solvents
      is equally predisposed to these hazards. In this study, we evaluated the
      mutagenicity of urine from 29 subjects exposed occupationally to solvents in a
      chemistry research laboratory and 29 subjects without occupational exposure
      (controls). Urine samples were collected in polyethylene containers at the end of
      the work shift. For the concentration and extraction of urine samples the XAD-2
      resin was used with acetone as an eluting agent. Several strains of Salmonella
      typhimurium (TA100, TA98, TA97a, TA1535, YG1024) should be used to assess
      mutagenic susceptibilities among workers exposed to organic solvents. Different
      doses of extract (1.5; 3.0; 6.0 and 12.0 ml equivalents of urine per plate) were
      tested on S. typhimurium strains TA100 and YG1024, with and without metabolic
      activation. The mutagenic activity, measured in Salmonella typhimurium YG1024
      with S9 mix, was significantly greater in urine from workers than from controls
      (p<or=0.05). These results indicate the relevance of using biomarkers to assess
      the risk of occupational exposure to organic solvents.

PMID- 18716395
TI  - Severe complications of bronchoscopy.
AB  - BACKGROUND: Interventional bronchoscopy is widely used for the diagnosis and
      therapy of many lung and airway diseases. Concern has been raised about its
      complications. OBJECTIVE: To review the severe complications associated with
      bronchoscopy. METHODS: A retrospective review of clinical records of 23,862
      patients who underwent bronchoscopic examination or therapy from December 1983 to
      December 2004 in our department. Severe complications associated with
      bronchoscopic examination or therapy were analyzed. RESULTS: During the study
      period, among 23,862 cases, 152 cases experienced severe complications; 3 cases
      died; the rate of severe complications was 0.637%; mortality rate was 0.013%. The
      complications included laryngeal, tracheal and bronchial spasm in 68 cases,
      hematorrhea in 37 cases, arrhythmia in 19 cases, airway obstruction in 8 cases,
      esophagotracheal fistula in 5 cases, pneumothorax in 4 cases, tracheal
      perforation in 3 cases, death in 3 cases. CONCLUSIONS: Bronchoscopy is a safe
      procedure. The increased rate of severe complications and death associated with
      bronchoscopy may be ascribed to the increasingly wide use of bronchoscopy.

PMID- 18716396
TI  - Durable remission of Sezary syndrome after unrelated bone marrow transplantation
      by reduced-intensity conditioning.
AB  - A 22-year-old Japanese man was diagnosed with Sezary syndrome with large cell
      transformation. His skin lesions persisted after treatment with 7 cycles of CHOP
      (cyclophosphamide, doxorubicin, vincristine and prednisone), psoralen and
      ultraviolet light A, and total skin electron beam irradiation. He subsequently
      underwent allogeneic bone marrow transplantation by reduced-intensity
      conditioning from a human leukocyte antigen-identical unrelated donor. He
      developed grade II of acute graft-versus-host disease and extensive-type chronic
      graft-versus-host disease. He has no signs of disease 36 months after the
      transplantation. The prognosis of patients with advanced stage of mycosis
      fungoides or Sezary syndrome is very poor. Allogeneic hematopoietic stem cell
      transplantation, especially by reduced-intensity conditioning, is expected to
      become a curative treatment option, and graft-versus-tumor effect might play a
      critical role for sustained remission.

PMID- 18716397
TI  - Antitumor activity of bortezomib alone and in combination with TRAIL in human
      acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is a malignant disease characterized by abnormal
      proliferation of clonal precursor cells. Although different strategies have been
      adopted to obtain complete remission, the disease actually progresses in about 60
      70% of patients. Bortezomib has been used in multiple myeloma and other lymphoid
      malignancies because of its antitumor activity. Here we examined the sensitivity
      of bone marrow cells from AML patients (34 patients: 25 newly diagnosed, 4
      relapsed, 5 refractory) to bortezomib alone or in combination with TRAIL, a
      member of the TNF family that induces apoptosis in tumor cells while sparing
      normal cells. Bortezomib induced cell death in blasts from each patient sample.
      The cytotoxic effect was dose- and time-dependent (concentration from 0.001 to 10
      microM for 24 and 48 h) and was associated with a downregulation of Bcl-xL and
      Mcl-1, an upregulation of TRAIL-R1, TRAIL-R2, p21, activation of executioner
      caspases and a loss of the mitochondrial membrane potential. Moreover, low doses
      of bortezomib primed TRAIL-resistant AML cells for enhanced TRAIL-mediated
      killing. These results suggest that a combination of proteasome inhibitors and
      TRAIL could be effective for treating AML patients, even patients who are
      refractory to conventional chemotherapy.

PMID- 18716398
TI  - Analysis of the association of preeclampsia with polymorphisms of the INS, INSR
      and IRS1 genes in Mexican women.
AB  - BACKGROUND/AIMS: It has been proposed that preeclampsia is a metabolic syndrome
      of pregnancy. The polymorphisms PstI and MaeIII of INS, NsiI of INSR and
      Ala513Pro and Gly972Arg of IRS1 have been associated with metabolic syndrome;
      moreover, the products of these genes are functionally contiguous during insulin
      signaling. The aim of this study was to assess whether these polymorphisms are
      associated with preeclampsia. METHODS: 46 normotensive pregnant women and 43
      preeclamptic patients were included in the study to develop a clinical,
      biochemical and genotypic profile of preeclampsia. Clinical evaluation consisted
      of measurement of blood pressure, height and weight. Peripheral blood samples
      were collected for determination of fasting glucose and insulin concentrations
      and for extraction of genomic DNA. Proteinuria was determined. Polymorphisms were
      detected using PCR-RFLP. RESULTS: The normotensive and preeclampsia groups did
      not differ significantly in clinical and biochemical traits, except for systolic
      and diastolic blood pressure (p < 0.0001). Polymorphisms previously associated
      with metabolic syndrome in Mexican populations were not associated with
      preeclampsia in Mexican women (p > 0.05). CONCLUSION: The lack of an association
      between preeclampsia and the polymorphisms studied suggests that other genes
      whose products do not have direct functional interaction with metabolic syndrome
      or epigenetic factors may play a role in preeclampsia.

PMID- 18716399
TI  - Correlation of quality of life with clinical parameters and eosinophilic cation
      protein levels in children with allergic rhinoconjunctivitis.
AB  - BACKGROUND: Systemic and mucosal roles of eosinophils in the pathogenesis of
      allergic rhinoconjunctivitis (AR) are known. The aim of this study was to
      investigate the relationship of clinical parameters and quality of life with
      eosinophilic cationic protein (ECP) in grass pollen-sensitive children with
      seasonal AR. METHODS: This study included 31 children with AR and 18 healthy
      controls aged between 5 and 15 years. ECP levels in nasal lavage fluid and serum
      were measured. AR symptom scores were calculated and the pediatric
      rhinoconjunctivitis quality of life questionnaire (PRQLQ) was filled in for all
      patients. RESULTS: Mean serum and nasal ECP levels (ng/ml) were significantly
      higher in the patient group (p < 0.05 for both). In the AR group, the mean
      clinical symptom score was 7.3 +/- 2.2, while the total PRQLQ score, activity
      limitation, symptoms and emotional function domains were 2.5 +/- 0.9, 3.0 +/-
      1.1, 2.5 +/- 1.2 and 2.6 +/- 1.1, respectively. The total clinical symptom score
      and disease duration showed a significant correlation with the total PRQLQ score
      (p = 0.00 and 0.003, respectively). However, neither nasal lavage nor serum ECP
      levels were significantly correlated with symptom score, duration of disease,
      PRQLQ total score or domains (p > 0.05 for all). CONCLUSION: These results may
      indicate the absence of a correlation between clinical status and quality of life
      and levels of ECP in tissues with allergic inflammation.

PMID- 18716400
TI  - Can the use of HEPA cleaners in homes of asthmatic children and adolescents
      sensitized to cat and dog allergens decrease bronchial hyperresponsiveness and
      allergen contents in solid dust?
AB  - BACKGROUND: Exposure and sensitization to pet allergens are associated with
      allergic asthma in children. Conflicting data have emerged regarding the
      potential benefit of air cleaners with respect to a reduction of indoor pet
      allergens and bronchial hyperresponsiveness (BHR). METHODS: In a randomized
      controlled trial 36 asthmatic children with sensitization to cat and/or dog and
      significant exposure to cat and/or dog allergen (Fel d 1 and/or Can f 1 >500 ng/g
      of carpet dust) were included in order to study the effect of high-efficiency
      particulate arresting (HEPA) air cleaners placed in the living room and bedroom
      compared with the effect of sham air cleaners. Patients were allocated to two
      groups: group 1 exposed to active filters and group 2 exposed to sham filters. At
      month 0, after 6 months and after 12 months, pulmonary function testing and cold
      air challenge were performed, serum eosinophil cationic protein (ECP) and
      specific IgE to seven aeroallergens were determined, and carpet dust samples and
      filters were collected. Major pet allergen concentrations (Fel d 1, Can f 1) were
      determined in filters and bulk dust samples. RESULTS: Thirty patients completed
      the study. After 6 and 12 months, there was no significant change in delta FEV(1)
      after cold air challenge, or in the use of medication and serum ECP levels.
      However, there was a trend in the active group towards an improvement of
      bronchial hyperresponsiveness, whereas the sham filter group showed a
      deterioration of BHR. CONCLUSION: Although HEPA air cleaners retained airborne
      pet allergens, no effect on disease activity or allergen concentrations in bulk
      dust samples was observed in this study.

PMID- 18716401
TI  - Changes in RANTES and beta-thromboglobulin after intensive exercise in patients
      with allergic asthma.
AB  - BACKGROUND: There is increasing evidence that exercise-induced
      bronchoconstriction (EIB) is associated with eosinophilic airway inflammation. In
      the pathogenesis of EIB the role of chemokines - responsible for promoting the
      migration and activation of inflammatory cells - as well as blood platelets, a
      potential source of those chemokines, remains unclear. METHODS: The study was
      conducted in a group of 19 asthmatics (11 with EIB, 8 without EIB) and 8 healthy
      volunteers. Changes in the plasma concentrations of RANTES and beta
      thromboglobulin (beta-TG) induced by intensive exercise were determined.
      Moreover, the possible correlation of these measurements with the results of
      other tests used in the diagnosis of asthma as well as laboratory tests commonly
      associated with asthma were investigated. RESULTS: A comparison of the
      concentrations of beta-TG in all groups studied at rest did not reveal any
      significant differences. In all groups studied, 30 min after exercise elevated
      beta-TG concentrations were observed; the most significant increase was revealed
      in asthmatics with EIB. The baseline concentrations of RANTES before exercise in
      both groups of asthmatics were significantly higher in comparison to the group of
      healthy volunteers. After exercise, in the group of patients with EIB, a
      significant increase in RANTES concentrations was observed. These changes
      correlated with an increase in other markers of airway inflammation 24 h after
      exercise. CONCLUSIONS: We suggest that platelet activation, resulting in elevated
      RANTES release, could be one of the factors responsible for the increase of
      airway inflammation observed in consequence of EIB in asthmatics.

PMID- 18716402
TI  - IgE-mediated occupational asthma from epoxy resin.
AB  - BACKGROUND: Epoxy resins (ERs) are used in paints and other protective coatings,
      including flooring materials. Bisphenol A diglycidyl ether (BADGE) ERs (BADGE
      ERs) account for about 75% of the ERs used world-wide. ERs can cause both
      immediate and delayed allergic reactions, but immediate reactions are rare.
      METHODS: Occupational asthma (OA) was diagnosed on the basis of a specific
      challenge test combined with the patient's history of occupational exposure and
      respiratory symptoms. RESULTS: A 39-year-old nonsmoking construction worker
      experienced dyspnea when laying ER-containing floors, but not in other
      situations. He also presented skin symptoms. IgE-mediated allergy to BADGE ER
      could be verified with both serum IgE antibodies and skin prick tests. The
      specific bronchial challenge test with BADGE ER caused an immediate asthmatic
      reaction. On patch testing, a positive reaction was provoked by BADGE ER.
      CONCLUSIONS: This is the first study on a patient exposed to BADGE ER with IgE
      mediated immediate OA, based on a positive inhalation challenge test. If work
      related respiratory symptoms develop when handling ERs, the possibility of OA
      should be recognized.

PMID- 18716403
TI  - Lactobacillus rhamnosus GG and Lactobacillus casei suppress Escherichia coli
      induced chemokine expression in intestinal epithelial cells.
AB  - BACKGROUND: Recently, some strains of lactic acid bacteria (LAB) have been
      reported to prevent the development of atopic dermatitis and to improve allergic
      symptoms, especially in young children. However, the mechanisms involved in these
      effects are not fully understood. Intestinal microbiota play critical roles in
      the development of host immune development and are recognized and regulated by
      the host through intestinal epithelial cells (IECs). We thus hypothesized that
      LAB influence the host immune system through the activation of IECs. To begin
      testing this hypothesis, chemokine expression in IECs exposed to intestinal
      bacteria was investigated. METHODS: Caco-2 cell monolayers were stimulated with
      different concentrations of various live or heat-killed intestinal bacteria or
      bacterial components for up to 3 h. Changes in the gene expressions of various
      chemokines were measured using quantitative real-time PCR. RESULTS: The
      expressions of CCL20, CXCL8, CXCL10 and CX3CL1 were strongly induced by
      nonpathogenic Escherichia coli in a dose-dependent manner and were partially
      induced by some commensal LAB. In contrast, Lactobacillus rhamnosus GG (LGG) and
      Lactobacillus casei did not induce these chemokine expressions. In addition, LGG
      significantly suppressed the expressions of CCL20 and CXCL10 induced by E. coli,
      peptidoglycan or flagellin when cultured simultaneously. CONCLUSIONS: LGG and L.
      casei markedly suppressed E. coli-induced chemokine expression, presumably
      through the suppression of the Toll-like receptor-mediated signal transduction
      pathway, at least in part. The clinical importance of this suppressive effect and
      the mechanisms involved require further investigation; however, such effects can
      be used as a marker to identify clinically useful LAB.

PMID- 18716404
TI  - Allergenicity of sigma and delta class glutathione S-transferases from the German
      cockroach.
AB  - BACKGROUND: Cockroach glutathione S-transferases (GSTs) are known to elicit
      strong IgE responses. This study was undertaken to compare the IgE reactivity of
      German cockroach GSTs, Bla g 5 (sigma class) and delta class GST (BgGSTD1).
      METHODS: Full-length Bla g 5 and BgGSTD1 were cloned, and their recombinant
      proteins were expressed and purified. Their IgE reactivities and cross
      reactivities were examined by ELISA using sera from cockroach-sensitized
      subjects. RESULTS: A predominant variant of Bla g 5 cDNA has amino acid
      substitutions at positions 10 (C to F) and 42 (N to K). BgGSTD1 has substitutions
      at positions 27 (E to N) and 207 (K to R). Sera from cockroach-sensitized
      patients showed 20.5% IgE reactivity to Bla g 5 and 17.9% IgE reactivity to
      BgGSTD1. However, inhibition studies using 1 serum sample with the highest IgE
      reactivity showed limited cross-reactivity. CONCLUSIONS: IgE-binding frequency to
      the cockroach GSTs was low, but the titer of IgE reactivity was strong in some
      sera. The inclusion of different classes of GSTs could be helpful for the
      delicate diagnosis and immunotherapy of cockroach allergy.

PMID- 18716405
TI  - Allergic sensitization to bovine beta-lactoglobulin: comparison between germ-free
      and conventional BALB/c mice.
AB  - BACKGROUND: The 'hygiene hypothesis' suggests that high hygienic standards met in
      western countries lead to a lack of microbial exposure, thus promoting the
      development of atopy by preventing the proper maturation of the immune system.
      Germ-free animals are deprived of the immune stimulation that occurs during
      postnatal gut colonization by commensal bacteria. Germ-free mice could thereby
      provide an attractive model for studying the impact of gut microbiota on the
      development of Th2-mediated disorders such as allergy. METHODS: Germ-free and
      conventional BALB/c mice were sensitized to beta-lactoglobulin (BLG), a major
      cow's milk allergen, by means of intraperitoneal injections in the presence of
      incomplete Freund's adjuvant. Time courses of serum and fecal BLG-specific
      antibody responses were monitored and cytokine production was assayed in BLG
      reactivated splenocytes. RESULTS: Serum BLG-specific IgG1 and IgE concentrations
      were significantly higher in germ-free mice during the primary immune response
      and IgE production persisted longer in germ-free mice. Furthermore, secretion of
      BLG-specific IgA was evidenced only in feces from germ-free mice while, in
      contrast, fecal IgG1 concentrations were at least 3-fold higher in conventional
      mice than in germ-free mice. Production of IL-5, IL-10 and IFN-gamma was 3-fold
      enhanced in BLG-reactivated splenocytes from germ-free mice. CONCLUSION: The
      absence of gut microbiota significantly affects the BLG-specific immune response
      in BALB/c mice, thus suggesting that this model might be of interest for further
      studies exploring the influence of gut colonization by different bacterial
      strains on the development of an allergic-type sensitization.

PMID- 18716406
TI  - Haplotype analysis of the NADPH oxidase p22 phox gene in patients with bronchial
      asthma.
AB  - BACKGROUND: Superoxide produced by airway epithelial and inflammatory cells may
      contribute to the pathogenesis of asthma. NADPH oxidase (an enzyme complex made
      up of 5 subunits) is a major source of superoxide in cells. We sought to
      elucidate the role of genetic variability in the gene encoding the p22(phox)
      subunit of the NADPH oxidase (CYBA, 16q24.3) in asthma susceptibility by means of
      an association study of haplotypes based on 3 common single nucleotide
      polymorphisms (SNPs), -930A/G, 242C/T (H72Y) and 640A/G. METHODS: SNPs were
      genotyped by PCR-RFLP methods in a cohort of age- and sex-matched subjects with
      bronchial asthma (n = 305) and healthy controls (n = 311). Haplotypes were
      constructed in silico using a Monte Carlo-based algorithm. Furthermore,
      association of SNPs with sensitization to selected allergens (total 15 tested by
      skin prick test positivity/negativity) was analyzed. RESULTS: In a single locus
      analysis, SNPs 242C/T and 640A/G were marginally significantly associated with
      asthma (p = 0.036 and 0.036, respectively). SNP 640A/G showed a significant
      association with sensitization to 2 allergens tested (p(corr) < 0.02). Haplotype
      analysis identified a total of 8 haplotypes with population frequencies from 0.07
      to 0.22. Distribution of haplotypes significantly differed between cases and
      controls (omnibus p = 0.017, 10,000 permutations). In the post-hoc analysis,
      haplotype CYBA(3) (-930G/242T/640A) was associated with an increased risk of
      asthma (p(corr) < 0.05; OR = 1.43, 95% CI 1.06-1.93). CONCLUSIONS: This study
      supports the hypothesis that genetic variability in the CYBA gene probably
      contributes to the susceptibility to bronchial asthma (or its related phenotypes)
      in our population.

PMID- 18716407
TI  - Familial aggregation of skin sensitization to aeroallergens in a rural area in
      China.
AB  - BACKGROUND: The prevalence of allergic sensitization has increased all over the
      world during last years and allergic sensitization may be related to genetic or
      environmental factors or to both. The objective of this study was to estimate the
      prevalence rates of allergic sensitization and assess the familial aggregation of
      allergic sensitization to aeroallergens in asthma index families. METHODS: The
      skin prick test (SPT) reactivity to 8 aeroallergens and the SPT reactivity
      related risk factors were evaluated. The allergic sensitization was based on SPT.
      Univariate and multivariate logistic regressive models were used to estimate the
      effect size (odds ratio, OR) of correlation within families with positive SPT.
      RESULTS: Of 4,213 analyzed subjects in 1,006 asthma index families, 40.9% had at
      least one positive SPT, 42.3% in parents (father: 43.3%; mother: 42.3%), 43.9% in
      first offspring, and 36.0% in subsequent offspring. The most common allergens
      were Dermatophagoides pteronyssinus (DP), cockroach and Dermatophagoides farinae
      (DF). Allergic sensitization status of both parents and first offspring was
      related to the risk of allergic sensitization for subsequent offspring. The OR
      for the positive (father)-positive (first offspring) group was 1.92 (p < 0.01),
      3.26 (p < 0.01) for the positive (mother)-positive (first offspring) group, and
      2.12 (p < 0.01) for the positive (father)-positive (mother) group, which were
      adjusted for age, sex, body mass index, history of asthma and smoking status.
      CONCLUSIONS: Our findings supported a significant familial aggregation of
      allergic sensitization in this Chinese population and highlighted the role of
      genetic factors in allergic sensitization.

PMID- 18716408
TI  - Epidemiology, characteristics and distinctiveness of headaches in children from
      Vojvodina, Serbia.
AB  - From 1988 to 2004, an investigation was carried out on a population of 30,636
      children (50.38% boys and 49.62% girls) in 9 towns of Vojvodina, province in
      northern Serbia. Idiopathic recurrent headache was found in 27.46% of children
      aged 3-17 years (26.8% of males and 28.4% of females). Migraine headache was
      found in 8.63% of children aged 3-17 years (8.0% of males and 9.6% of females).
      Recurrent headaches showed an occurrence that increased with age in the observed
      group, from 16.65 to 32.87% in boys and from 14.23 to 40.50% in girls (ages 3-5
      and >12 years, respectively). Of the children with migraine, 25.55% had migraine
      with aura, 67.21% had migraine without aura and 7.23% had other migraine types.
      Idiopathic recurrent headache was found in children at a mean age of 9 years and
      2.5 months (range 3-17 years). The presence of both recurrent and migraine
      headaches was found to be higher than previously described. In children, these
      headaches appear to be significantly associated with incomplete families, a poor
      economic situation and being the second-born child. Children with recurrent
      headache were diagnosed and followed by a general practitioner in 31.5% of cases,
      by a pediatrician in 21.6% and by a neurologist or neuropediatrician in the
      remaining 46.8%. Normal daily activity was compromised in children with recurrent
      headache for 3.91 days per year.

PMID- 18716409
TI  - The prevalence of multiple sclerosis in the Middle East.
AB  - BACKGROUND: The prevalence of multiple sclerosis (MS) in the Middle East has been
      reported to be low to medium. METHODS: To verify this assertion we conducted a
      review of published data on the occurrence of MS in the Middle East. RESULTS:
      Fourteen studies reporting on the prevalence of MS in the Middle East were
      initially identified, 5 of which were excluded due to inadequate data or serious
      methodological limitations. The data from the 9 included studies suggested that
      the prevalence of MS may vary widely within the Middle East, from low to high.
      However, these 9 studies were inconsistent in case ascertainment, inclusion
      criteria and methods of prevalence calculation, and most did not include age/sex
      standardization. CONCLUSION: Methodological inconsistencies among studies make it
      difficult to be confident in drawing conclusions about the prevalence of MS in
      the Middle East. Nevertheless, there is little evidence to support the assertion
      that the prevalence of MS in the Middle East is low to medium. Rather, the
      prevalence of MS in the Middle East may range from low to high, depending on the
      specific population and environment of study. However, to confirm these findings,
      further epidemiological research is needed.

PMID- 18716410
TI  - Body mass index, cholesterol level and poststroke mortality.

PMID- 18716412
TI  - Clinical parameters to predict response to interferon in relapsing multiple
      sclerosis.
AB  - BACKGROUND: To identify clinical parameters of response to beta-interferon (IFN
      beta) in relapsing-remitting multiple sclerosis (RRMS) from an East France
      cohort. METHODS: Data from 2,645 patients, identified by Burgundy and Lorraine
      multiple sclerosis (MS) networks, were computerized by a neurologist using the
      European Database for MS software. Patient inclusion criteria were: clinically or
      laboratory-supported definite RRMS according to Poser's diagnostic criteria and
      treatment with IFN-beta for at least 6 months. Four criteria were chosen to
      predict a response to IFN-beta. The first criterion was any patient who had a
      lower annualized relapse rate under IFN-beta therapy than during the year
      preceding treatment; the second criterion was a lower relapse rate than during
      the 2 years preceding treatment. The third was any patient free of relapse during
      the first 2 years of IFN-beta therapy. The last criterion concerned the variation
      in the degree of disability measured by the Disability Status Scale during the
      first year of treatment. Multivariate logistic regression analyses were
      performed. RESULTS: 751 RRMS cases were included. A higher relapse rate in the
      year preceding IFN-beta onset, an older age at MS onset and having a
      polysymptomatic onset of MS were significantly associated with a response for the
      first criterion. With the 3 other criteria, no parameter predicting response was
      identified. CONCLUSION: Only the relapse rate in the year before initiation of
      IFN-beta treatment appears to be able to predict response to treatment but not
      the one of 2 years before.

PMID- 18716413
TI  - The treatment of multiple sclerosis with beta-interferon.

PMID- 18716411
TI  - Environmental epidemiology of essential tremor.
AB  - BACKGROUND: Essential tremor (ET) is one of the most common neurological
      disorders. Despite this, the disease mechanisms and etiology are not well
      understood. While susceptibility genotypes undoubtedly underlie many ET cases, no
      ET genes have been identified thus far. As with many other progressive,
      degenerative neurological disorders, it is likely that environmental factors
      contribute to the etiology of ET. Environmental epidemiology is the study in
      specific populations or communities of the effect on human health of physical,
      biologic and chemical factors in the external environment. The purpose of this
      article is to review current knowledge with regards to the environmental
      epidemiology of ET. RESULTS: As will be discussed, a series of preliminary case
      control studies in recent years has begun to explore several candidate
      toxins/exposures, including harmane (1-methyl-9H-pyrido[3,4-b]indole), lead and
      agricultural exposures/pesticides. CONCLUSIONS: While several initial results are
      promising, as will be discussed, additional studies are needed to more
      definitively establish whether these exposures are associated with ET and if they
      are of etiological importance.

PMID- 18716414
TI  - Effect of folic acid combined with fluoxetine in patients with major depression
      on plasma homocysteine and vitamin B12, and serotonin levels in lymphocytes.
AB  - OBJECTIVE(S): Folic acid, a micronutrient supporting the natural defense system,
      may elevate antidepressant responses, although the lymphocyte serotonergic system
      has not been explored in folate-supplemented depressed patients. METHODS: Twenty
      seven patients were randomly assigned to groups receiving fluoxetine (20 mg) and
      folic acid (10 mg/day) or fluoxetine and placebo for 6 weeks. Clinical outcome
      was assessed according to the Hamilton Depression Rating Scale (HDRS) at the
      beginning, during and at the end of treatment. Blood samples were taken, plasma
      was separated, and lymphocytes were obtained by density gradient centrifugation
      with Ficoll/Hypaque and differential adhesion to plastic dishes. Fifteen healthy
      subjects served as controls. Plasma folate, homocysteine and vitamin B12, and
      serotonin concentration in lymphocytes were determined by HPLC. The HDRS score
      was significantly lower in patients receiving fluoxetine and folic acid compared
      with those receiving fluoxetine and placebo after 6 weeks of treatment (7.43 +/-
      1.65 vs. 11.43 +/- 1.31, respectively; p = 0.04). Plasma homocysteine
      statistically significant decreased after folic acid (p = 0.02), but no
      significant changes were observed in vitamin B12. RESULTS: Serotonin was
      significantly reduced after fluoxetine either with folate (p = 0.03) or placebo
      (p = 0.01) probably by the effect of transporter blockade. 5-Hydroxyindoleacetic
      acid was lower in lymphocytes of patients receiving folate (p = 0.04), indicating
      a reduced turnover rate, thus accumulating serotonin in the cells. A significant
      negative correlation was noted between homocysteine and folate. No significant
      correlations were present among biochemical parameters and depression severity.
      CONCLUSION: Modifications due to treatment with fluoxetine and folic acid may
      alter lymphocyte function in depression probably indirectly by reducing
      homocysteine levels and directly on lymphocytes by modifying the serotonergic
      system.

PMID- 18716415
TI  - Abdominal surgery performed under general anesthesia increases somatostatin-like
      immunoreactivity in human serum.
AB  - OBJECTIVE: It has been established in animals that somatostatin (SST) is released
      from pain-activated sensory nerve endings and exerts systemic antinociceptive and
      anti-inflammatory actions. The aim of this study was to investigate the changes
      of SST-like immunoreactivity (SST-LI) in human serum before, immediately after
      and 2 h after surgical operations. METHODS: 25 patients were enrolled in the
      study. Laparoscopic cholecystectomy, abdominal wall hernia or inguinal hernia
      operations were performed under combined anesthesia. A 5-ml blood sample was
      drawn from each patient, the blood was centrifuged and the serum frozen. SST-LI
      was determined from the defrosted samples by radioimmunoassay. RESULTS: Abdominal
      surgical operationsinduced a significant increase of SST-LI in the serum. 2 h
      later it was restored in the cases of laparoscopic interventions but still
      remained elevated after hernia surgeries. CONCLUSIONS: In this human study we
      showed for the first time that surgical interventions elevate the endogenous SST
      LI in human serum. It is assumed that the released SST is derived from the
      activated sensory nerves. Since antinociceptive and anti-inflammatory effects of
      neural SST have already been established in laboratory animals, we presume that
      this endogenous protective mechanism also operates in humans.

PMID- 18716416
TI  - Timing-dependent effects of restraint stress on eosinophilic airway inflammation
      in mice.
AB  - BACKGROUND: Chronic stress has been proposed to aggravate allergic inflammation,
      whereas acute stress may have functional beneficial effects. The aim of this
      study was to investigate the influence of timing of single short restraint stress
      (RST) in a model of eosinophilic airway inflammation. METHODS: The airways of
      ovalbumin (OVA)-sensitized mice were exposed to an intranasal OVA challenge. RST
      was applied in two different ways; either 2 h before (pre-stress) or after (post
      stress) the OVA challenge, respectively, or as a combination of stress before and
      after (double-stress) the OVA challenge. One group of mice was also treated with
      metyrapone (ME) prior to a pre-stress challenge. The inflammatory cell response
      was evaluated in bronchoalveolar lavage fluid (BALF), lung and nasal tissue, as
      well as bone marrow. RESULT: RST applied prior to the OVA challenge (pre-stress)
      inhibited OVA-induced airway inflammation in BALF and lung tissue, and reduced
      nasal histopathology compared to unstressed mice. Given as post-stress or double
      stress, RST did not affect the inflammation in BALF, lungs or nasal tissue. Pre
      treatment with ME prevented the pre-challenge stress evoked decrease in
      inflammation in BALF and lungs. CONCLUSION: Effects of RST on eosinophilic airway
      inflammation appear to be strongly dependent on timing and, as could be judged
      from the ME inhibition pattern, also corticosterone dependent. Hypothalamic
      pituitary-adrenal axis activation probably influences eosinophilic inflammation
      through specific sequences of compartmental activation and thereby timing effects
      are evident on cellular recruitment pattern during the allergic reaction.

PMID- 18716417
TI  - Clinicopathological significance of caspase-8 and caspase-10 expression in rectal
      cancer.
AB  - OBJECTIVES: To investigate the expression of caspase-8 and -10 in rectal adenoma,
      adenocarcinoma and the corresponding normal mucosa tissue, and to clarify the
      relationship between their expression and clinicopathological parameters of
      rectal cancer. METHODS: The expression of caspase-8 and -10 was determined by
      real-time RT-PCR and immunohistochemistry in 36 rectal adenomas, 93 rectal
      cancers and 93 corresponding normal rectal mucosa samples. RESULTS: Compared with
      normal mucosa, the mRNA expression of caspase-8 was higher in adenomas (p =
      0.003), while that of caspase-10 was lower in adenomas (p = 0.035) and cancers (p
      = 0.001). Immunohistochemical results showed caspase-8 up-regulation in adenomas
      (p = 0.014), and caspase-10 down-regulation in adenomas (p = 0.034) and cancers
      (p < 0.001) compared with normal mucosa samples. Cancers with poor
      differentiation had lower caspase-10 mRNA and protein levels than those with
      better differentiation (p = 0.041 and p = 0.046, respectively). The protein
      expression of caspase-8 and -10 was in accordance with the mRNA expression (p =
      0.043 and p = 0.018, respectively). CONCLUSIONS: Caspase-8 expression was up
      regulated in rectal adenomas. Caspase-10 expression was down-regulated in both
      rectal adenomas and cancers, and was further related to differentiation. Caspase
      8 and -10 may be involved in the pathogenesis of rectal cancer.

PMID- 18716418
TI  - Infectious port complications are more frequent in younger patients with
      hematologic malignancies than in solid tumor patients.
AB  - BACKGROUND: We assessed longevity and complications of totally implantable venous
      access devices in oncology patients. METHODS: 197 patients received a total of
      201 port devices via the subclavian vein for delivery of chemotherapy between
      January 1, 2005, and December 31, 2006. We reviewed the patient charts for port
      related complications and risk factors until July 31, 2007. RESULTS: A total of
      47,781 catheter days were analyzed (median, 175 days; range, 1-831). Forty-six
      different complications occurred (0.96 complications/1,000 catheter days). The
      only risk factor significantly associated with a higher complication rate was
      younger age. Older patients had a lower risk for developing complications with a
      risk reduction of 2.4% for each year. There were no differences regarding
      underlying tumor, gender, access side, method of placement (subclavian/cephalic
      vein) or implanting team (thoracic versus visceral surgery). A trend was seen for
      shorter port longevity in hematologic patients compared to oncologic patients (p
      = 0.059). The former developed significantly more port-associated infections than
      solid tumor patients [11/53 cases (21%) versus 2/148 cases (1.4%); p < 0.0001].
      CONCLUSIONS: Port-associated infections were mostly observed in younger patients
      with hematologic neoplasms. Prospective trials should be performed to evaluate
      the benefit of a prophylactic antimicrobial lock in these selected patients.

PMID- 18716419
TI  - Sorafenib: tolerance in patients on chronic hemodialysis: a single-center
      experience.
AB  - BACKGROUND/OBJECTIVE: Improved understanding of renal cell carcinomas (RCC) and
      recent contributions in the field of RCC biology led to the development of a
      novel class of drugs, i.e. multiple-kinase inhibitors, targeting growth factor
      receptors (e.g. sorafenib). Sorafenib has proven significant benefit in terms of
      progression-free survival in a phase II trial in RCC patients. A subsequent
      randomized phase III study (Treatment Approaches in Renal Cancer Global
      Evaluation Trial) confirmed the significantly prolonged progression-free survival
      and improvement in the quality of life compared to patients receiving placebo. In
      the USA and Europe, sorafenib has been approved for the treatment of advanced
      RCC. PATIENTS: Two RCC patients on chronic hemodialysis were treated with
      sorafenib. RESULTS: Both patients responded to sorafenib treatment. Apart from
      high blood pressure, a major adverse effect of sorafenib treatment, treatment was
      well tolerated, in agreement with previous results. CONCLUSION: The results of
      our study confirm the beneficial effect of sorafenib in the treatment of RCC in
      our 2 patients on dialysis.

PMID- 18716422
TI  - Minor psychiatric disorders and syncope: the role of psychopathology in the
      expression of vasovagal reflex.
AB  - BACKGROUND: A high prevalence of minor psychiatric disorders (MPDs) has been
      reported in patients with vasovagal syncope (VVS). However, the relationship
      between the psychiatric substrate and syncope remains unclear. METHODS: In order
      to test the hypothesis that MPDs may predispose to VVS, we assessed the
      prevalence of syncope, the response to head-up tilt test (HUTT) and the efficacy
      of psychiatric drug treatment in reducing syncopal episodes, in patients with
      recently diagnosed MPDs. The response to HUTT was compared with that in an equal
      number of matched (a) patients with VVS and (b) healthy controls. RESULTS: A high
      rate of patients with MPDs (58%) had a positive HUTT. Additionally, 45% had a
      history of syncope; among them, the rate of positive HUTT was identical to that
      in the VVS group (83%). Following psychiatric drug treatment, the number of
      patients with syncope decreased in the MPD group (6/67 from 30/67, p < 0.01).
      Psychiatric symptoms and quality of life were also improved. The number of
      syncopal spells decreased equally in the MPD and VVS groups (0.6 +/- 0.5 from 2.5
      +/- 1.4, p < 0.01, and 0.7 +/- 0.5 from 2.7 +/- 1.3, p < 0.01, respectively).
      CONCLUSION: A high proportion of patients with MPDs experience syncope,
      associated with a high rate of positive HUTT, comparable to that observed in VVS.
      Psychiatric treatment results in the improvement of syncopal and psychiatric
      symptoms. These findings suggest involvement of co-occurring MPDs in the
      pathogenesis of VVS. Therefore, the diagnosis and treatment of MPDs, when
      present, may be crucial for the effective therapy of vasovagal syndrome.

PMID- 18716423
TI  - Association between anxiety and factors of coagulation and fibrinolysis.
AB  - BACKGROUND: Psychological stress and anxiety have been shown to produce an
      activation of coagulation and fibrinolysis. Resulting hypercoagulability is a
      risk factor for cardiovascular diseases, and could therefore contribute to an
      increased prevalence of coronary artery disease in anxiety patients. However,
      hemostasis function has not yet been studied in patients with clinically relevant
      anxiety disorders. METHODS: A group of anxiety patients (panic disorder with
      agoraphobia or social phobia) and a healthy control group (each n = 29) completed
      some questionnaires [SCL-K9 (a short form of the SCL-90-R), State Trait Anxiety
      Inventory, ADS (general depression scale)], and had blood drawn after a 15-min
      rest period. To assess the reaction of the hemostatic system by global entities,
      sum scores were computed from parameters of coagulation and fibrinolysis
      (fibrinogen, FVII, FVIII, vWF, F1 + 2, TAT, D-dimer, alpha(2)-AP, PAP, tPA, PAI
      1). Interfering variables, such as age, gender, alcohol consumption and smoking
      status, were controlled. RESULTS: Anxiety patients scored higher in a composite
      hemostatic score and a sum score of fibrinolysis in comparison to the control
      group, with a predominant activation of inhibitors in fibrinolysis. However, the
      psychological variable with the closest association to hemostasis was not trait
      anxiety, but self-perceived worry about blood drawing before blood sampling was
      performed. CONCLUSIONS: The coagulation and fibrinolysis system is activated in
      the direction of a hypercoagulable state in patients with severe phobic anxiety,
      triggered by fear of blood drawing. This could be one mediating factor for the
      increased risk of cardiovascular diseases in this population. Acute situational
      phobic anxiety should be monitored closely when studying the association between
      anxiety and hemostasis.

PMID- 18716424
TI  - Clinical features and functioning of patients with minor depression.
AB  - BACKGROUND: The two essential features of minor depression are that it has fewer
      symptoms than major depression and that it is less chronic than dysthymia. This
      study describes the clinical features and functioning of outpatients with minor
      depression. METHODS: Subjects with minor depression (with and without a prior
      history of major depression) were recruited through clinical referrals and
      community advertising. Assessments included the Structured Clinical Interview for
      DSM-IV (SCID), the 17-item Hamilton Rating Scale for Depression (HAM-D), the
      Inventory of Depressive Symptomatology-Self Report (IDS-SR) and Clinician Rated
      (IDS-C) scales, the Global Assessment of Functioning (GAF) scale, the Medical
      Outcomes Study 36-item Short-Form scale (MOS), and the Clinical Global
      Impressions Severity Scale (CGI). Data from previously published studies of major
      depression, minor depression, and normal controls were compared to our data set.
      RESULTS: Minor depression is characterized primarily by mood and cognitive
      symptoms rather than vegetative symptoms; the functional impairment associated
      with minor depression is as severe as for major depression in several areas;
      minor depression occurs either independently of major depression or as a stage of
      illness during the long-term course of major depression, and minor depression
      patients with and without a history of major depression have similar levels of
      depressive severity and functional impairment. CONCLUSIONS: These findings
      support the notion that minor depression is an important clinical entity that
      fits within the larger spectrum of depressive disorders.

PMID- 18716425
TI  - Functional impairment in patients with remitted bipolar disorder.

PMID- 18716426
TI  - Outcome of additional behaviour therapy including treatment discontinuation for
      fluvoxamine non-responders with obsessive-compulsive disorder.

PMID- 18716427
TI  - [Early results of treatment of proximal humerus fractures with the PHILOS locking
      plate].
AB  - OBJECTIVES: The aim of this study was to evaluate early results of proximal
      humerus fractures treated with the PHILOS locking plate. METHODS: Proximal
      humerus fractures of 22 patients (13 males, 9 females; mean age 57 years; range
      35 to 83 years) were treated with the PHILOS locking plate. According to the Neer
      classification, 13 patients had comminuted fractures, four patients had valgus
      impact injuries, two patients had fracture-dislocations, and three patients had
      fractures involving the proximal 1/3 of the humerus. The fractures were reduced
      by the transdeltoid lateral approach (n=8) using minimally invasive surgery, and
      by the anterior deltopectoral approach (n=14) using open surgery. Passive and
      active exercises were initiated on the second postoperative day and after 4 to 6
      weeks, respectively. The results were assessed using the Constant-Murley shoulder
      scoring system. The mean follow up was 14 months (range 12 to 19 months).
      RESULTS: Radiographically, union was observed in 20 patients at the end of 10
      weeks. In one patient, time to union was 16 weeks. One patient underwent
      autogenous bone grafting because of nonunion after 16 weeks. The mean Constant
      Murley score was 75.5 (range 51 to 93). There was no significant difference
      between Constant-Murley scores of patients undergoing the transdeltoid lateral
      and anterior deltopectoral approaches (p>0.05). Plate fixation was associated
      with minimal varus deformity in two patients, and subacromial impingement in one
      patient. Implant failure did not occur. Reflex sympathetic dystrophy and
      avascular necrosis were observed in two patients, respectively. CONCLUSION:
      Fixation with the PHILOS plate is a near-ideal technique with a high union rate
      in the treatment of proximal humeral fractures.

PMID- 18716428
TI  - [Treatment of pediatric displaced supracondylar humerus fractures by fixation
      with two cross K-wires following reduction achieved after cutting the triceps
      muscle in a reverse V-shape].
AB  - OBJECTIVES: We evaluated the results of surgical treatment for pediatric
      displaced supracondylar humerus fractures. METHODS: The study included 98
      pediatric patients (72 boys, 26 girls; mean age 7 years; range 3 months to 14
      years). According to the Gartland classification, all the displaced supracondylar
      humerus fractures were type III, being of flexion type in 10 patients (10.2%),
      and extension type in 88 patients (89.8%). Five were Gustilo-Anderson type 1 open
      fractures. All fractures were approached posteriorly. Reduction was achieved by
      cutting the triceps muscle in a reverse V-shape, followed by fixation using two
      cross K-wires from the epicondyles. The results were assessed according to the
      criteria of Flynn et al. At final follow-ups, elbow range of motion, the strength
      of the triceps muscle and, on radiographs, the carrying angle of the elbow,
      Baumann angle, and lateral humerocapitellar angle were measured. The mean follow
      up was 42.6 months (range 7 to 80 months). RESULTS: According to the criteria of
      Flynn et al., 95 patients (96.9%) had perfect or good cosmetic results, 84
      patients (85.7%) had perfect or good functional results. Elbow angles, elbow
      range of motion, and the strength of the triceps muscle were similar to those
      measured on the normal side (p>0.05). Time from injury to surgery did not have a
      significant influence on cosmetic and functional results (p>0.05). None of the
      patients exhibited procedure-related pin tract infection or insufficient bone
      union. Three patients (3.1%) developed cubitus varus deformity. CONCLUSION:
      Reduction of pediatric displaced supracondylar humerus fractures may be achieved
      easily by the posterior approach, after cutting the triceps muscle in a reverse V
      shape, and fixation with two cross-pinned K-wires provides adequate stability.
      This procedure does not result in weakness of the triceps muscle.

PMID- 18716429
TI  - [A new technique for aneurysmal bone cysts of the proximal humerus: cortical
      collapsing].
AB  - OBJECTIVES: We evaluated the results of a new technique developed for aneurysmal
      bone cysts centrally located in the proximal humeral metaphysis leading to
      widespread destruction. METHODS: The study included seven patients (5 boys, 2
      girls; mean age 12.8 years; range 9 to 15 years) who were treated with cortical
      collapsing and massive fibular autograft for centrally located aneurysmal bone
      cysts in the proximal humeral metaphysis leading to widespread destruction. All
      the patients had type II and active tumors according to the criteria of Capanna
      et al. and Campanacci et al., respectively. Final evaluations included six
      patients because one patient was lost to follow-up. The mean follow-up period was
      49 months (range 12 to 105 months). RESULTS: No complications were seen in the
      early postoperative period. Radiographic examination showed partial recurrence in
      two patients; of whom, one patient underwent curettage and bone grafting in the
      postoperative second year because of pain and discomfort. No deformity was
      observed. One patient developed shortening of 0.5 cm. Radiographically, all the
      patients exhibited metaphyseal remodelling one year after surgery. Function of
      the shoulder joint was near-normal in all the patients. CONCLUSION: In this
      technique, cortical collapsing reduces the amount of bone graft used, and massive
      fibular strut grafting provides structural support to prevent deformities.

PMID- 18716430
TI  - [Childhood injuries, their etiologies, and preventive measures].
AB  - OBJECTIVES: The purpose of this study was to evaluate social, economical, and
      cultural factors of childhood injuries and to assess preventive measures.
      METHODS: The study included 120 children (75 boys, 45 girls; mean age 8.3 years;
      range 0 to 14 years) who presented to the emergency department due to trauma from
      September to December 2007. Information was gathered from the patients or parents
      on the following: age, number of siblings; time, etiology, place, and type of
      trauma; type and time of transportation, educational and sociocultural level of
      the parents, and whether the patient had a similar injury before. RESULTS: About
      one-tenth (10.8%) of the patients were admitted and treated. Twenty patients
      (16.7%) had at least one similar injury previously. Most of the events were
      household injuries (n=42, 35%). The highest number of injuries occurred at the
      ages of 7, 8, and 10 years, and the number of injuries remained high from 12 to
      14 years of age. The most frequent site of injury was the elbow during the first
      six years of age, the wrist and the hand at ages 7 to 11 years, and the wrist
      from 12 to 14 years of age. The great majority of the mothers were housewives
      (86.7%). Occupation and educational status of the mother, and the number of
      siblings were not related with recurrent childhood injuries (p>0.05). CONCLUSION:
      This study provided helpful information on the characteristics of childhood
      trauma. Programs targeting to increase the awareness on pertinent risk behaviors
      and to promote educational efforts concerning the risks and preventive measures
      will be of great help in preventing childhood injuries, in particular at the
      beginning of school life (age 7) and adolescence (age 12), at which time child
      injuries show culmination.

PMID- 18716431
TI  - [Partial removal of nail matrix in the treatment of ingrowing toe nail].
AB  - OBJECTIVES: Ingrowing toe nail is a frequent disorder of the foot. In this study,
      we evaluated the results of surgical treatment of ingrowing toe nail. METHODS:
      Sixty-two patients (31 males, 31 females; mean age 38 years; range 11 to 72
      years) with ingrowing toe nail underwent partial removal of the nail matrix
      according to the Winograd technique. The presenting complaints were pain, foul
      smelling drainage, deformity, and difficulty in walking. According to the
      Heifetz's staging system, 18 patients had stage I, 23 patients had stage II, and
      21 patients had stage III disease. Forty-four patients had active drainage due to
      an infectious process. The infected cases were operated on after improvement of
      inflammation by antibiotic treatment. One patient underwent excision of subungual
      exocytosis causing severe deformity of the toe. Time to return to work, time to
      recurrence, and patient satisfaction were evaluated. The mean follow-up period
      was 26 months (range 24 to 42 months). RESULTS: Recurrence was seen in four
      patients (6.5%) within a mean of 4.2 months (range 3 to 7 months). The remaining
      patients returned to normal daily activities after a mean of 12 days (range 10 to
      16 days). The mean time to work was five days (range 3 to 16 days). All but two
      patients who developed recurrences expressed satisfaction with surgery. None of
      the patients had deep infection or neurovascular complications. CONCLUSION:
      Partial removal of the nail matrix is associated with a very low recurrence rate
      and a higher rate of patient satisfaction.

PMID- 18716432
TI  - [Early results of autologous mononuclear bone marrow cell implantation in
      nontraumatic avascular necrosis of the femoral head].
AB  - OBJECTIVES: We evaluated early clinical and radiologic results of core
      decompression combined with autologous mononuclear bone marrow cell implantation
      for early stage nontraumatic avascular necrosis of the femoral head. METHODS: The
      study included nine patients (1 female, 8 males, mean age 46.5 years; range 33 to
      59 years) with stage I-II nontraumatic avascular necrosis of the femoral head,
      according to the Steinberg classification. Bone marrow-derived CD34 cells were
      injected through a core decompression channel into the femoral head. Clinical
      assessment included a visual analog scale (VAS), Harris hip score, and the WOMAC
      Osteoarthritis Index. Radiologically, femoral head collapse, narrowing of the
      coxofemoral joint space, and the size of the osteonecrotic area were assessed.
      The mean follow-up was 27.2 months (range 24 to 38 months). RESULTS: Pre- and
      postoperative (24th month) evaluations showed that the mean VAS score and the
      WOMAC Osteoarthritis Index decreased from 3.4+/-0.4 to 1.2+/-0.6, and from 33+/-3
      to 11+/-6, respectively, with an increase in the Harris hip score (from 54 to
      92). Preoperatively, two patients were Steinberg I-B, four were I-C, and three
      were II-A. Finally, all the patients were stage 0 except for one patient who
      regressed to I-A. None of the patients exhibited femoral head collapse or
      narrowing of the coxofemoral joint space. CONCLUSION: Autologous mononuclear bone
      marrow cell implantation relieves articular pain, prevents the progression of
      osteonecrosis, and hence subchondral fractures. Therefore, it may be treatment of
      choice particularly in stage I-II avascular necrosis of the femoral head.

PMID- 18716433
TI  - [Short-term results of treatment of tennis elbow with anti-inflammatory drugs
      alone or in combination with local injection of a corticosteroid and anesthetic
      mixture].
AB  - OBJECTIVES: We compared the short-term results of anti-inflammatory drugs alone
      or in combination with local injection of a corticosteroid and anesthetic mixture
      in the treatment of tennis elbow. METHODS: The study included 21 patients (12
      males, 9 females; mean age 45 years; range 19 to 72 years) with tennis elbow. The
      patients were randomized to oral and topical anti-inflammatory drugs alone (group
      1, n=10) or combined with a single local injection of a corticosteroid and
      anesthetic mixture (group 2, n=11). The patients were evaluated with a pain score
      (0 to 10 points) and clinical examination before and one month after treatment.
      RESULTS: Complete or near-complete relief of pain and unlimited function were
      obtained in four patients (40%) in group 1, and in 10 patients (90.9%) in group
      2. On physical examination, two patients (20%) in group 1 and eight patients
      (72.7%) in group 2 were pain-free upon pressure on the lateral epicondyle or
      dorsiflexion of the wrist. Pain scores differed significantly in both groups
      after treatment (p=0.026 and p=0.003, respectively); however, combination
      treatment was associated with a significantly higher efficacy (p=0.036).
      CONCLUSION: It was concluded that significantly enhanced efficacy of the
      combination treatment used in this study might be limited to the short-term and
      that adverse effects of steroids on the tendons should be taken into
      consideration.

PMID- 18716434
TI  - [Surgical management of unstable both-bone forearm fractures in children].
AB  - OBJECTIVES: We evaluated the results of two different surgical methods for the
      treatment of unstable both-bone forearm fractures in children. METHODS: Thirty
      five children with unstable both-bone forearm fractures were retrospectively
      evaluated. Of these, 14 patients (group 1; 4 girls, 10 boys; mean age 13 years;
      range 10 to 15 years) underwent open reduction and plate-screw fixation, and 21
      patients (group 2; 5 girls, 16 boys; mean age 11.5 years; range 8 to 13 years)
      underwent closed reduction and intramedullary fixation. All the fractures in
      group 1 were closed, while, in group 2, there were 15 closed and six type 1 open
      fractures. The mean time to surgery was 4.3 days in group 1, and 3.1 days in
      group 2. The results were assessed using the criteria of Price et al. The mean
      follow-up was 34 months in group 1, and 37 months in group 2. RESULTS: Nonunion
      was observed in only one patient in group 1. The mean time to union was 7.2 weeks
      (range 6 to 11 weeks) in group 1, and 6.5 weeks (range 6 to 10 weeks) in group 2.
      According to the criteria of Price et al., the results in group 1 were perfect in
      11 patients (78.6%), good in two patients (14.3%), and fair in one patient
      (7.1%). In group 2, 18 patients (85.7%) had excellent, three patients (14.3%) had
      good results. Complications were major in three patients (21.4%) and minor in two
      patients (14.3%) in group 1, compared to one major (4.8%) and eight minor (38.1%)
      complications in group 2. None of the patients had limb-length discrepancy, joint
      deformity, angular or rotational deformity, or complications such as synostosis
      and infection. CONCLUSION: It was concluded that intramedullary nailing was safe,
      effective, and easy to perform in the management of unstable both-bone forearm
      fractures in children.

PMID- 18716435
TI  - [In which period of skeletal muscle ischemia-reperfusion injury is local
      hypothermia more effective?].
AB  - OBJECTIVES: We investigated the potential beneficial effects of local hypothermia
      applied during different periods of ischemia-reperfusion injury in a rat model.
      METHODS: An isolated gracilis muscle model of ischemia-reperfusion injury was
      used consisting of four groups, each with six rats. Ischemic injury was induced
      by clamping the femoral artery for six hours. Local hypothermia at 10 degrees C
      was applied during only ischemia (IH), during reperfusion (RH) for four hours,
      and during both ischemia and reperfusion (IRH). The control group remained
      untreated. After 24 hours of perfusion, the rats were sacrificed and the gracilis
      muscles were removed to determine muscle edema (wet-to-dry weight ratio),
      polymorphonuclear leukocytes (PMNL), and the percentage of necrosis. RESULTS:
      Compared to the control group (193.7 +/-38.9), the PMNL count was significantly
      lower in the IH, RH, and IRH groups (111.5+/-36.2, p<0.004; 82+/-18.6, p<0.002;
      54.5+/-21.8, p<0.002, respectively). The only significant difference in the PMNL
      count was between the IH and IRH groups (p<0.004). In all the hypothermia groups,
      the percentage of necrosis was found significantly less than that of the control
      group (22.5+/-5.2% vs 11.7+/-5.2% in IH, p<0.004; 10.8+/-3.8% in RH, p<0.004;
      6.7+/-2.6% in IRH, p<0.002).Similarly, muscle edema was significantly decreased
      in the study groups (control, 2.89+/-0.46 vs 2.01+/-0.26 in IH, p<0.001; 1.98+/
      0.34 in RH, p<0.001; 1.97+/-043 in IRH, p<0.001). There were no significant
      differences between the three hypothermia groups with respect to the percentage
      of necrosis and muscle edema. CONCLUSION: Our results show that local hypothermia
      applied during ischemic and reperfusion periods is significantly effective in
      reducing ischemia-reperfusion injury.

PMID- 18716436
TI  - [The effect of debridement performed before capsular plication on biomechanical
      properties of the knee joint capsule: an experimental study in rabbits].
AB  - OBJECTIVES: The purpose of this study was to evaluate early postoperative
      biomechanical changes in plicated joint capsules and to determine the effect of
      debridement to create a bleeding inner capsular surface on the healing process.
      METHODS: Fifty-four mature New Zealand white rabbits were used. Plication was
      performed in unilateral medial knee joint capsules of 48 rabbits either alone
      (n=24) or following debridement (n=24) to create a bleeding inner capsular
      surface. Six rabbits remained untreated for the control group. The operated knee
      joints were immobilized in flexion postoperatively. The rabbits from the two
      study groups were sacrificed in groups of six immediately after operation, in the
      first, second, and third weeks, of which five were evaluated in tensile tests and
      one was evaluated histologically. RESULTS: Compared to the controls, tensile
      strengths were significantly higher in both study groups until the third week
      (p<0.01), after which the difference became insignificant (p>0.05). The strength
      of the plicated capsules was significantly higher in the first week in both study
      groups than those measured in subsequent weeks (p<0.01), whereas similar tensile
      strengths were recorded in the second and third weeks (p>0.05). Compared to its
      absence, the use of debridement was associated with a significantly lower
      strength in the first week (p<0.01), but this difference was not observed
      afterwards (p>0.05). Histological findings were similar in the two study groups
      and were characterized by healing with increased fibrosis starting from the first
      week. CONCLUSION: A plicated capsule would not be weaker than an intact one. Our
      findings do not favor debridement for a more rapid and better healing process.
      Rather, it might have adverse effects on the biomechanical properties of the
      capsule.

PMID- 18716437
TI  - [Cervical schwannoma presenting with trauma-induced neurological symptoms].
AB  - A 37-year-old man was admitted with neurological complaints after a traffic
      accident. Physical examination showed no signs of injury due to the accident.
      Magnetic resonance imaging of the neck revealed a well-demarcated lesion showing
      homogeneous contrast enhancement at the level of C(1-2). The patient underwent
      elective surgery, and histopathological diagnosis of the surgical specimen was
      made as cervical schwannoma. His neurological complaints disappeared on the
      second postoperative day. No neurological deficit was observed at six-month
      follow-up. To our knowledge, there has been no literature report in which the
      diagnosis of cervical schwannoma was made during investigation of trauma-induced
      neurological symptoms.

PMID- 18716438
TI  - [Removal of a bent inflatable femoral nail: a case report].
AB  - Intramedullary nailing is the gold standard for the treatment of diaphyseal
      femoral fractures. Bending of the nail secondary to trauma is a rare complication
      encountered in unhealed and comminuted fractures. A 23-year-old man was admitted
      with refracture of the right femoral shaft and a 32-degree bending of an
      inflatable intramedullary nail due to a fall, two months after the initial
      surgical treatment. The nail was first straightened by exerting an external
      force, which decreased the angulation to 10 degrees. Then, the fracture site was
      opened, the lateral wall of the nail was drilled, and one of the four metal bars
      of the nail was cut. This allowed complete straightening of the nail by the same
      maneuver and its removal. A new inflatable intramedullary nail was placed and
      union was achieved after four months. Tools that may be necessary to cut the nail
      partially or totally should be made available for removal of bent nails.

PMID- 18716439
TI  - [Tuberculosis of the knee joint: a case report].
AB  - Tuberculosis may develop in the skeletal system apart from its primary location,
      the lungs. A 22-year-old male patient presented with complaints of severe pain
      and swelling in the left knee and difficulty in walking. The symptoms first
      appeared 12 years before and he underwent open surgical debridement and
      arthroscopic debridement at two other centers, at which time aspiration cultures
      taken from the knee yielded no growth. Physical examination showed a painful left
      knee with swelling, increased temperature, effusion, and limited range of motion.
      Based on history, physical examination, radiological studies, and laboratory
      findings, knee osteoarthritis was considered secondary to nonspecific septic
      arthritis and knee arthrodesis was performed. At surgery, marked destruction of
      articular cartilage and synovial hypertrophy were observed. In addition, a
      cavitary lesion was detected, about 1 x 1 cm in size, in the lateral femoral
      condyle without articular involvement. Biopsy cultures taken from the lesion
      showed growth of Mycobacterium tuberculosis in the third week. This enabled a
      diagnosis of tuberculosis of the knee joint and antituberculous drug therapy was
      instituted. At six months postoperatively, the patient was on antituberculous
      treatment and had a painless knee.

PMID- 18716440
TI  - [Re: Osteomusculocutaneous flap for clavicular reconstruction: a case report].

PMID- 18716442
TI  - Immunohistochemical identification and quantitative analysis of cytoplasmic Cu/Zn
      superoxide dismutase in mouse organogenesis.
AB  - Cytoplasmic Cu/Zn superoxide dismutase (SOD1) is an antioxidant enzyme that
      converts superoxide to hydrogen peroxide in cells. Its spatial distribution
      matches that of superoxide production, allowing it to protect cells from
      oxidative stress. SOD1 deficiencies result in embryonic lethality and a wide
      range of pathologies in mice, but little is known about normal SOD1 protein
      expression in developing embryos. In this study, the expression pattern of SOD1
      was investigated in post-implantation mouse embryos and extraembryonic tissues,
      including placenta, using Western blotting and immunohistochemical analyses. SOD1
      was detected in embryos and extraembryonic tissues from embryonic day (ED) 8.5 to
      18.5. The signal in embryos was observed at the lowest level on ED 9.5-11.5, and
      the highest level on ED 17.5-18.5, while levels remained constant in the
      surrounding extraembryonic tissues during all developmental stages examined.
      Immunohistochemical analysis of SOD1 expression on ED 13.5-18.5 revealed its
      ubiquitous distribution throughout developing organs. In particular, high levels
      of SOD1 expression were observed in the ependymal epithelium of the choroid
      plexus, ganglia, sensory cells of the olfactory and vestibulocochlear epithelia,
      blood cells and vessels, hepatocytes and hematopoietic cells of the liver, lymph
      nodes, osteogenic tissues, and skin. Thus, SOD1 is highly expressed at late
      stages of embryonic development in a cell- and tissue-specific manner, and can
      function as an important antioxidant enzyme during organogenesis in mouse
      embryos.

PMID- 18716443
TI  - Disposition kinetics and urinary excretion of ciprofloxacin in goats following
      single intravenous administration.
AB  - We evaluated the pharmacokinetics of ciprofloxacin in serum (n = 6) and urine (n
      = 4) in goats following a single intravenous administration of 4 mg/kg body
      weight. The serum concentration-time curves of ciprofloxacin were best fitted by
      a two-compartment open model. The drug was detected in goat serum up to 12 h. The
      elimination rate constant (beta) and elimination half-life (t1/2beta) were 0.446
      +/- 0.04 h(-1) and 1.630 +/- 0.17 h, espectively. The apparent volume of
      distribution at steady state (Vdss) was 2.012 +/- 0.37 l/kg and the total body
      clearance (ClB) was 16.27 +/- 1.87 ml/min/kg. Urinary recovery of ciprofloxacin
      was 29.70% +/- 10.34% of the administered dose within 36 h post administration.
      In vitro serum protein binding was 41% +/- 13.10%. Thus, a single daily
      intravenous dose of 4 mg/kg is sufficient to maintain effective levels in serum
      and for 36 h in urine, allowing treatment of systemic, Gram-negative bacterial
      infections and urinary tract infections by most pathogens.

PMID- 18716441
TI  - All blood, no stool: enterohemorrhagic Escherichia coli O157:H7 infection.
AB  - Enterohemorrhagic Escherichia coli serotype O157:H7 is a pathotype of
      diarrheagenic E. coli that produces one or more Shiga toxins, forms a
      characteristic histopathology described as attaching and effacing lesions, and
      possesses the large virulence plasmid pO157. The bacterium is recognized
      worldwide, especially in developed countries, as an emerging food-borne bacterial
      pathogen, which causes disease in humans and in some animals. Healthy cattle are
      the principal and natural reservoir of E. coli O157:H7, and most disease
      outbreaks are, therefore, due to consumption of fecally contaminated bovine foods
      or dairy products. In this review, we provide a general overview of E. coli
      O157:H7 infection, especially focusing on the bacterial characteristics rather
      than on the host responses during infection.

PMID- 18716444
TI  - Effect of dihydrotestosterone on mouse embryonic stem cells exposed to H2O2
      induced oxidative stress.
AB  - Oxidative stresses induced by reactive oxygen species (ROS) have been shown to be
      involved in several physiological and pathophysiological processes, such as cell
      proliferation and differentiation. Steroid hormones can protect cells against
      apoptosis or induce cell proliferation by several mechanisms. Among androgenic
      hormones, dihydrotestosterone (DHT) is generated by a 5alpha- reduction of
      testosterone. Unlike testosterone, DHT cannot be aromatized to estradiol,
      therefore DHT is considered a pure androgenic steroid. This study was conducted
      to examine the effect of DHT (10(-7) M) on H2O2 (10(-3) M) -induced injuries in
      mouse embryonic stem (ES) cells. H2O2 induced ROS generation and increased lipid
      peroxide formation and DNA fragmentation. These effects of H2O2 were inhibited by
      pretreatment with DHT. H2O2 also increased the phosphorylation of p38 MAPK,
      SAPK/JNK and nuclear factor kappa B (NF-kappaB), but DHT blocked these effects.
      Moreover, H2O2 decreased DNA synthesis and the levels of cell cycle regulatory
      proteins [cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4]. These
      effects of H2O2 were inhibited by pretreatment with DHT. In conclusion, DHT may
      partially prevent H2O2-induced cell injury through inhibition of ROS and ROS
      induced activation of p38 MAPK, SAPK/JNK and NF-kappaB in mouse ES cells.

PMID- 18716445
TI  - Plasma haptoglobin and immunoglobulins as diagnostic indicators of deoxynivalenol
      intoxication.
AB  - This study aimed to discover potential biomarkers for dioxynivalenol (DON)
      intoxication. B6C3F1 male mice were orally exposed to 0.83, 2.5 and 7.5 mg/kg
      body weight (bw) DON for 8 days and the differential protein expressions in their
      blood plasma were determined by SELDI - Time-of-Flight/Mass Spectrometry (TOF/MS)
      and the immunoglobulins (Igs) G, A, M and E in the serum were investigated. 11.7
      kDa protein was significantly highly expressed according to DON administration
      and this protein was purified by employing a methyl ceramic HyperD F column with
      using optimization buffer for adsorption and desorption. The purified protein was
      identified as a haptoglobin precursor by peptide mapping with using LC/Q-TOF/MS
      and MALDI-TOF/MS and this was confirmed by western blotting and ELISA. IgG and
      IgM in serum were decreased in a dose-dependent manner and IgA was decreased at
      7.5 mg/kg bw DON administration, but the IgE level was not changed. To compare
      the expressions of haptoglobin and the Igs patterns between aflatoxin B1 (AFB1),
      zearalenone (ZEA) and DON intoxications, rats were orally administered with AFB1
      1.0, ZEA 240 and DON 7.5 mg/kg bw for 8 days. Haptoglobin was increased only at
      DON 7.5 mg/kg bw, while it was slightly decreased at ZEA 240 mg/kg bw and it was
      not detected at all at AFB1 1.0 mg/kg bw. IgG and IgA were decreased by DON, but
      IgG, IgA, IgM and IgE were all increased by AFB1. No changes were observed by ZEA
      administration. These results show that plasma haptoglobin could be a diagnostic
      biomarker for DON intoxication when this is combined with examining the serum
      Igs.

PMID- 18716446
TI  - The inhibitory effect of quercitrin gallate on iNOS expression induced by
      lipopolysaccharide in Balb/c mice.
AB  - Quercetin 3-O-beta-(2(")-galloyl)-rhamnopyranoside (QGR) is a naturally occurring
      quercitrin gallate, which is a polyphenolic compound that was originally isolated
      from Persicaria lapathifolia (Polygonaceae). QGR has been shown to have an
      inhibitory effect on nitric oxide (NO) production in lipopolysaccharide (LPS)
      stimulated macrophage RAW 264.7 cells. Therefore, this study was conducted to
      investigate the inhibitory effect of QGR on nitric oxide production and inducible
      nitric oxide synthases (iNOS) expression in LPS-stimulated Balb/c mice. To
      accomplish this, 10 mg/kg of QGR was administered via gavage once a day for 3
      days. iNOS was then induced by intraperitoneal injection of LPS. Six hours after
      the LPS treatment the animals were sacrificed under ether anethesia. The serum
      levels of NO were then measured to determine if QGR exerted an inhibitory effect
      on NO production in vivo. LPS induced an approximately 6 fold increase in the
      expression of NO. However, oral administration of QGR reduced the LPS induced
      increase in NO by half. Furthermore, RT-PCR and western blot analysis revealed
      that the increased levels of iNOS expression that occurred in response to
      treatment with LPS were significantly attenuated in response to QGR pretreatment.
      Histologically, LPS induced the infiltration of polymorphonuclear neutrophils in
      portal veins and sinusoids and caused the formation of a large number of necrotic
      cells; however, pretreatment with QGR attenuated these LPS induced effects. Taken
      together, these results indicate that QGR inhibits iNOS expression in vivo as
      well as in vitro and has antiinflammatory potentials.

PMID- 18716447
TI  - Evaluation of the effect of a 3rd GnRH injection administered six days after the
      2nd GnRH injection of Ovsynch on the reproductive performance of Japanese black
      cows.
AB  - This study was designed to evaluate the reproductive performance of Japanese
      black cows following the 3rd injection of gonadotropin releasing hormone (GnRH)
      analogue administered concurrently with Ovsynch-based treatment on day 6 (day 1 =
      the day of ovulation). In Experiment 1, 12 cows were allocated into three groups:
      a control group that was subjected to Ovsynch treatment and then injected with a
      placebo on day 6; group 1 (Ovsynch + GnRH), which was subjected to Ovsynch
      treatment and was injected with GnRH analogue on day 6, and group 2 (Ovsynch +
      controlled internal drug-release (CIDR) + GnRH), which received Ovsynch-CIDR
      treatment and was injected with GnRH analogue on day 6. Blood collection and
      ultrasonographic observation of the ovaries were conducted daily. Both treatments
      induced the formation of an accessory corpus luteum and significantly increased
      the cross-sectional area of the luteal tissue when compared to the control.
      However, plasma progesterone (P4) was significantly higher in the treatment
      groups than in the control group on days 11, 12, 17 and 18 in the group 1 and
      from day 10 to 21 in the group 2. In Experiment 2, 41 cows were assigned to the
      same three groups described above and then artificially inseminated on day 1. The
      pregnancy rates on day 45 did not differ among groups. In conclusion,
      administration of GnRH analogue on day 6 following Ovsynch-based treatment did
      not improve the reproductive performance of Japanese black cows, even though the
      P4 concentration was higher in groups that received the GnRH.

PMID- 18716448
TI  - The radioprotective effects of the hexane and ethyl acetate extracts of
      Callophyllis japonica in mice that undergo whole body irradiation.
AB  - The radioprotective activity of extracts from the red seaweed Callophyllis (C.)
      japonica was investigated in mice that underwent whole-body exposure to gamma
      radiation. A methanol extract of C. japonica and its fractions [hexane, ethyl
      acetate (EtOAc), butanol and the remaining H2O] were used. Each fraction (100
      mg/kg body weight) was administered intraperitoneally (i.p.) 2 times into the
      BALB/c mice, once at 1 and once at 24 h before exposure to 9 Gray (Gy) of gamma
      radiation. Pre-irradiation administration of the hexane and EtOAc fractions saved
      the mice, with their survival rates being greater than 80% at 30 days post
      irradiation; the mice that were pretreated with the other fractions showed
      survival rates lower than 20% over the same time period. To examine the effect of
      each C. japonica fraction on the survival of intestinal and bone marrow stem
      cells, the number of intestinal crypts and bone marrow cells in the gamma
      irradiated mice were examined. Pre-treatment of mice (i.p., 100 mg/kg body weight
      at 1 and 24 h before irradiation) with the hexane or EtOAc fraction prior to 6-Gy
      irradiation significantly protected the number of jejunal crypts and bone marrow
      cells at 9 days after irradiation. These findings suggest that certain extracts
      from C. japonica, when they are administered prior to irradiation, play an
      important role in the survival of irradiated mice, and this is possibly due to
      the extracts protecting the hematopoietic cells and intestinal stem cells against
      gamma irradiation.

PMID- 18716449
TI  - Microbial pathogens in ticks, rodents and a shrew in northern Gyeonggi-do near
      the DMZ, Korea.
AB  - A total of 1,618 ticks [420 individual (adults) and pooled (larvae and nymphs)
      samples], 369 rodents (Apodemus agrarius, Rattus norvegicus, Tscherskia triton,
      Mus musculus, and Myodes regulus), and 34 shrews (Crocidura lasiura) that were
      collected in northern Gyeonggi-do near the Demilitarized Zone (DMZ) of Korea
      during 2004-2005, were assayed by PCR for selected zoonotic pathogens. From a
      total of 420 individual and pooled tick DNA samples, Anaplasma (A.)
      phagocytophilum (16), A. platys (16), Ehrlichia (E.) chaffeensis (63), Borrelia
      burgdorferi (16), and Rickettsia spp. (198) were detected using species-specific
      PCR assays. Out of 403 spleens from rodents and shrews, A. phagocytophilum (20),
      A. platys (34), E. chaffeensis (127), and Bartonella spp. (24) were detected with
      species-specific PCR assays. These results suggest that fevers of unknown causes
      in humans and animals in Korea should be evaluated for infections by these vector
      borne microbial pathogens.

PMID- 18716451
TI  - Protection of chickens from Newcastle disease with a recombinant baculovirus
      subunit vaccine expressing the fusion and hemagglutininneuraminidase proteins.
AB  - Recombinant baculoviruses containing the fusion (F) and hemagglutinin
      neuraminidase (HN) glycoprotein gene of the viscerotropic velogenic (vv)
      Newcastle disease virus (NDV) isolate, Kr-005/00, and a lentogenic La Sota strain
      of the NDV were constructed in an attempt to develop an effective subunit vaccine
      to the recent epizootic vvNDV. The level of protection was determined by
      evaluating the clinical signs, mortality, and virus shedding from the oropharynx
      and cloaca of chickens after a challenge with vvNDV Kr-005/00. The recombinant ND
      F (rND F) and recombinant HN (rND HN) glycoproteins derived from the velogenic
      strain provided good protection against the clinical signs and mortality, showing
      a 0.00 PI value and 100% protection after a booster immunization. On the other
      hand, the combined rND F + HN glycoprotein derived from the velogenic strain
      induced complete protection (0.00 PI value and 100% protection) and significantly
      reduced the amount of virus shedding even after a single immunization. The rND F
      and rND HN glycoproteins derived from the velogenic strain had a slightly, but
      not significantly, greater protective effect than the lentogenic strain. These
      results suggest that the combined rND F + HN glycoprotein derived from vvNDV can
      be an ideal subunit marker vaccine candidate in chickens in a future ND
      eradication program.

PMID- 18716450
TI  - Protective efficacy of commercial inactivated Newcastle disease virus vaccines in
      chickens against a recent Korean epizootic strain.
AB  - Despite the intensive vaccination policy that has been put in place to control
      Newcastle disease virus (NDV), the recent emergence of NDV genotype VII strains
      in Korea has led to significant economic losses in the poultry industry. We
      assessed the ability of inactivated, oil-emulsion vaccines derived from La Sota
      or Ulster 2C NDV strains to protect chickens from challenge with Kr-005/00, which
      is a recently isolated Korean epizootic genotype VII strain. Six-week-old SPF
      chickens were vaccinated once and challenged three weeks later via the eye
      drop/intranasal route. All vaccinated birds were fully protected from disease,
      regardless of the vaccine strains used. All vaccinated and challenged groups
      showed significant sero-conversion 14 days after challenge. However, some
      vaccinated birds, despite being protected from disease, shed the challenge virus
      from their oro-pharynx and cloaca, albeit at significantly lower titers than the
      unvaccinated challenged control birds. The virological, serological, and
      epidemiological significance of our observations with regard to NDV disease
      eradication is discussed.

PMID- 18716452
TI  - Cytokine response in Balb/c mice infected with Francisella tularensis LVS and the
      Pohang isolate.
AB  - We investigated the immune response induced by the Francisella (F.) tularensis
      live vaccine strain (LVS) and the Pohang isolate. After the Balb/c mice were
      infected intradermally (i.d) with 2 x 10(4) cfu of F. tularensis LVS and Pohang,
      respectively, their blood and organs were collected at different times; 0, 3, 6,
      24, 72, 96, 120 and 168 h after infection. Using these samples, RT-PCR and ELISA
      analysis were carried out for the comparative study of the cytokines, including
      TNF-alpha, INF-gamma, IL-2, IL-4, IL-10 and IL-12. In the Pohang-infected mice at
      120 h, the liver showed a 53 times higher level of TNF-alpha and a 42 times
      higher level of IFN-gamma than the respective levels at the early time points
      after infection. The levels of TNF-alpha and IFN-gamma induced by LVS were 5
      times lower than those induced by the Pohang isolate. Also, the organs from the
      Pohang-infected mice showed higher levels of TNF-alpha, IFN-gamma, IL-10 and IL
      12 than the levels in the LVS-infected mice. The blood from the Pohang-infected
      mice at 120 h revealed about a 40 times increased level of IFN-gamma, and IL-10
      was also increased by 4 times at 96 h compared to an early infection time point,
      while IL-4 was not induced during the whole infection period. These results
      suggest that F. tularensis may induce a Th1-mediated immune response to in vivo
      infection and the Pohang isolate has a higher capacity than the LVS to induce an
      acute immune response in Blab/c mice.

PMID- 18716453
TI  - Evaluation of serum chondroitin sulfate and hyaluronan: biomarkers for
      osteoarthritis in canine hip dysplasia.
AB  - Hip dysplasia (HD) is one of the most important bone and joint diseases in dogs.
      Making the radiographic diagnosis is sometime possible when the disease has
      markedly progressed. Chondroitin sulfate (CS) and hyaluronan (HA) are the most
      important cartilage biomolecules that are elevated in the serum taken from dogs
      with osteoarthritis. The serum CS and HA can be detected by an ELISA technique,
      with using monoclonal antibodies against CS epitope 3B3 and WF6 and the HA chain
      as the primary antibodies. The aim of this study was to compare the levels of
      serum CS (both epitopes) and HA in non-HD and HD dogs. All 123 dogs were
      categorized into 2 groups. The non-HD group was composed of 98 healthy dogs,
      while the HD group was comprised of 25 HD dogs. Blood samples were collected for
      analyzing the serum CS and HA levels with using the ELISA technique. The results
      showed that the average serum level of the CS epitope WF6 in the HD group (2,594
      +/- 3,036.10 ng/ml) was significantly higher than that in the non-HD group (465
      +/- 208.97 ng/ml) (p < 0.01) while the epitope 3B3 in the HD group (105 +/-
      100.05 ng/ml) was significantly lower than that in the non-HD group (136 +/-
      142.03 ng/ml) (p < 0.05). The amount of serum HA in the HD group (134.74 +/-
      59.71 ng/ml) was lower than that in the non HD group (245.45 +/- 97.84 ng/ml) (p
      < 0.05). The results indicate that the serum CS and HA levels might be used as
      biomarkers for osteoarthritis in HD dogs.

PMID- 18716454
TI  - Distribution of the putative virulence factor encoding gene sheta in
      Staphylococcus hyicus strains of various origins.
AB  - In the present study, Staphylococcus (S.) hyicus strains isolated in Russia (n =
      23) and Germany (n = 17) were investigated for the prevalence of the previously
      described genes sheta and shetb. Sheta was detected in 16 S. hyicus strains.
      Sheta-positive strains were mainly found among strains isolated from exudative
      epidermitis, and frequently together with the exfoliative toxin-encoding genes
      exhD and exhC. Partial sequencing of sheta in a single S. hyicus strain revealed
      an almost complete match with the sheta sequence obtained from GenBank. None of
      the S. hyicus strains displayed a positive reaction with the shetb-specific
      oligonucleotide primer used in the present study. According to the present
      results, the exotoxin encoding gene sheta seems to be distributed among S. hyicus
      strains in Russia and Germany. The toxigenic potential of this exotoxin, which
      does not have the classical structure of a staphylococcal exfoliative toxin,
      remains to be elucidated.

PMID- 18716456
TI  - Surgical correction of pectus excavatum in two cats.
AB  - Two sexually intact male Bengal cats, one a 4-month-old weighing 2.8 kg and the
      other, a 3-month-old weighing 2.0 kg, were presented to the University of
      Missouri-Columbia Veterinary Teaching Hospital for evaluation of respiratory
      distress. On initial presentation, both cats were dyspneic, exercise intolerant,
      and had marked concave deformation of the caudal sternum. Surgical correction of
      pectus excavatum was performed using a cylindrical external splint and U-shaped
      external splint. Post-operative thoracic radiography revealed that there was
      decreased concavity of the sternum and increased thoracic height at the level of
      the caudal sternebrae in both cats.

PMID- 18716455
TI  - Malignant mixed tumor in the salivary gland of a cat.
AB  - The presence of a malignant mixed tumor, also known as a carcinosarcoma, in the
      salivary gland is very rare. Such tumors, which are typically aggressive, are
      characterized by the presence of carcinomatous and sarcomatous components. A 9
      year-old neutered female domestic short-haired cat presented with swelling in the
      right mandibular lesion that had rapidly enlarged over the previous 3 weeks.
      Physical examination revealed a large, fluctuated and painless subcutaneous
      swelling that was associated with a firm mass. Radiographs of the head revealed a
      soft-tissue density that involved faint circular calcific opacity. Contrast
      enhanced computed tomography revealed that the peripheral capsulated cystic area
      had a contrast enhanced region without bone lysis. The cat received a total
      excision of the mass and postoperative radiotherapy. Histopathological analysis
      of the mass revealed that it was a malignant mixed tumor. Metastasis to the lung
      was discovered 7 weeks later, at which time treatment was stopped.

PMID- 18716457
TI  - Selective mitochondrial autophagy during erythroid maturation.
AB  - Accumulating evidence suggests that autophagy can be selective in the clearance
      of organelles in yeast and in mammalian cells. We have observed that the
      sequestration of mitochondria by autophagosomes was defective in reticulocytes in
      the absence of Nix. Nix is required for the dissipation of mitochondrial membrane
      potential (DeltaPsim) during erythroid maturation. Moreover, pharmacological
      agents that induce the loss of DeltaPsim can restore the sequestration of
      mitochondria by autophagosomes and promote mitochondrial clearance in Nix(-/-)
      erythroid cells. Our data suggest that mitochondrial depolarization induces
      recognition and sequestration of mitochondria by autophagosomes. Elucidating the
      mechanisms underlying selective mitochondrial autophagy not only will help us to
      understand the mechanisms for erythroid maturation, but also may provide insights
      into mitochondrial quality control by autophagy in the protection against aging,
      cancer and neurodegenerative diseases.

PMID- 18716458
TI  - Autophagy induction as an efficient strategy to eradicate tumors.
AB  - The understanding of the mechanisms of cell-death execution and the role that
      they play in different diseases opens new therapeutic strategies. Currently,
      increasing evidence indicates that autophagy is a frequent cell-death mechanism,
      so the question arises: Could autophagy stimulation be considered an antitumor
      therapy? Several autophagy inducers have been used as anticancer agents and,
      although complete tumor eradication has not been demonstrated, the antitumor
      effect is very promising. We have recently demonstrated that strong autophagy
      stimulation mediated by the combined generation of cyanide and oxidative stress
      could efficiently suppress tumor growth in an aggressive brain cancer model such
      as glioblastoma. We have used the plant enzyme linamarase, which metabolizes the
      innocuous substrate linamarin to generate cyanide in a continuous and controlled
      way inducing mitochondrial fragmentation. Glucose oxidase addition induces
      oxidative stress that increases cell vacuolization. The combination of both
      insults favors mitochondrial engulfment by vacuoles accelerating cell death that
      is mediated by autophagy.

PMID- 18716480
TI  - An atypical meningioma.

PMID- 18716481
TI  - Biological treatment for degenerative disc disease: implications for the field of
      physical medicine and rehabilitation.
AB  - Spine care is a fast-growing sector of the outpatient practice for physiatrists.
      Current nonsurgical treatment modalities and surgical options for severe
      symptomatic intervertebral disc degeneration have limited and inconsistent
      clinical results. Thus, the development of novel approaches, such as biological
      treatments that offer the potential to halt or even reverse disc degeneration and
      restore physiologic disc function, are very attractive. In this article, we first
      review the structural changes that occur during intervertebral disc degeneration
      and their relationship with discogenic back pain. Subsequently, we review the
      treatment approaches currently under clinical trial and laboratory investigation.
      Physiatrists specializing in spine care have the skill set required for
      administering intradiscal injections and supervising a comprehensive
      rehabilitation program after the procedures. Ultimately, the clinical use of any
      biological treatment discussed herein would require the collective efforts of
      physicians (such as physiatrists and surgeons) and researchers (such as chemical
      and biomedical engineers, biologists, and chemists).

PMID- 18716482
TI  - Pre- and postoperative cardiopulmonary rehabilitation in hospitalized patients
      undergoing coronary artery bypass surgery: a randomized controlled trial.
AB  - OBJECTIVE: Patients who have to wait in the hospital for coronary artery bypass
      surgery (CABG) are exposed to the potential risks of immobilization. This
      clinical trial was conducted to evaluate the effects of an in-hospital
      cardiopulmonary rehabilitation program performed before and after CABG on
      postoperative outcomes. DESIGN: Fifty-six patients who had to wait for CABG in
      hospital were randomly assigned to a cardiopulmonary rehabilitation (Rehab; n =
      29) or to usual care (Control; n = 27). In the Rehab group, intervention lasted
      for at least 5 days preoperatively until discharge. The program consisted of
      phase I cardiac rehabilitation associated with respiratory physical therapy.
      Outcomes were blindly evaluated. RESULTS: By hospital discharge, Rehab patients
      presented a shorter time to endotracheal extubation (1054 +/- 376 vs. 1340 +/-
      666 min, P = 0.05), a reduction in the incidence of pleural effusion (relative
      risk [RR] = 0.2; 95% confidence interval [CI]: 0.5-0.8), atelectasis (RR = 0.15;
      95% CI: 0.03-0.8), pneumonia (0 vs. 7 cases, [P = 0.004]), and atrial
      fibrillation or flutter (RR = 0.2; 95% CI: 0.05-0.8). Length of in-hospital stay
      after surgery was also reduced in the Rehab group (5.9 +/- 1.1 vs. 10.3 +/- 4.6
      days [P < 0.001]). CONCLUSION: Pre- and postoperative cardiopulmonary
      rehabilitation in patients who await CABG in the hospital is superior to standard
      care and leads to a reduced rate of postoperative complications and shorter
      hospital stay.

PMID- 18716483
TI  - Lung insufflation capacity in neuromuscular disease.
AB  - OBJECTIVE: To compare maximal passive lung insufflation capacity (LIC) with lung
      inflation by air stacking (to maximum insufflation capacity [MIC]) and with vital
      capacity (VC); to explore relationships between these variables that correlate
      with glottic function and cough peak flows (CPF); to demonstrate the effect of
      routine inflation therapy on LIC and MIC; and to determine the relative
      importance of lung inflation therapy as a function of disease severity. DESIGN:
      Case series of 282 consecutive neuromuscular disease (NMD) clinic patients 7 yrs
      and older with VC <70% of the predicted normal value. All cooperative patients
      meeting these criteria were prescribed thrice-daily air stacking and/or maximal
      passive lung insufflation to pressures of 40-80 cm H2O, and they underwent
      measurements of VC, MIC, LIC, and unassisted and assisted CPF on every visit.
      RESULTS: Means +/- standard deviations for VC, MIC, and LIC were 1131 +/- 744,
      1712 +/- 926, and 2069 +/- 867 ml, respectively, and, for unassisted and assisted
      CPF, they were 2.5 +/- 2.0 and 4.3 +/- 2.2 liters/sec, respectively, with all
      differences statistically significant (P < 0.001). MIC minus VC correlated
      inversely with LIC minus MIC (P = 0.01) and, therefore, with glottic function.
      Both MIC and LIC increased with practice (P < 0.001). Increases in LIC but not
      MIC over VC were greatest for patients with the lowest VC (P < 0.05). There were
      no complications of lung mobilization therapy. CONCLUSIONS: Passive lung
      insufflation can distend the lungs of patients with NMD significantly greater
      than air stacking, particularly when glottic and bulbar-innervated muscle
      dysfunction is severe. LIC, MIC, and VC measurements permit quantifiable
      assessment of glottic integrity and, therefore, bulbar-innervated muscle function
      for patients with NMD. The patients who benefit the most from insufflation
      therapy are those who have the lowest VC.

PMID- 18716484
TI  - Cough augmentation in Duchenne muscular dystrophy.
AB  - OBJECTIVE: The purpose of this work was to compare the relative importance of
      deep lung insufflation with the abdominal thrust and their combination in
      augmenting cough peak flows (CPF). DESIGN: Unassisted CPF and CPF assisted by air
      stacking to deep lung volumes (CPFair), assisted by abdominal thrusts
      (CPFthrust), and assisted by both air stacking and abdominal thrusts (aCPF) were
      measured for 61 patients with Duchenne muscular dystrophy (DMD). RESULTS:
      Overall, mean unassisted CPF were 138 +/- 70 liters/min, CPFthrust were 204 +/-
      75 liters/min, CPFair were 236 +/- 68 liters/min, and aCPF were 302 +/- 78
      liters/min. The differences between each were statistically significant (P <
      0.0001). CONCLUSIONS: Thus, air stacking was significantly more effective than
      abdominal thrust in increasing CPF, but the combination was the most effective.
      The CPF of the quartile of patients with the lowest unassisted CPF were also
      significantly (P < or = 0.04) more augmented by air stacking and thrusting than
      for the milder quartiles of patients. Thus, the greatest improvements in CPF were
      for patients with the weakest coughs.

PMID- 18716485
TI  - Admission C-reactive protein does not predict functional outcomes in patients
      with strokes in a subacute rehabilitation unit.
AB  - OBJECTIVE: Because serum C-reactive protein (CRP) levels correlate with the
      extent of inflammatory reactions, including acute strokes, we tested whether
      serum CRP levels on admission to a stroke rehabilitation unit help to predict
      functional outcome at discharge. DESIGN: We measured serum CRP level within 72
      hrs of admission to an inpatient stroke rehabilitation unit in 102 successive
      patients transferred to rehabilitation within 4 wks following stroke and who met
      inclusion criteria. RESULTS: Patients with normal levels of serum CRP (< or =9.9
      mg/dl) on admission to our rehabilitation service were more likely to be
      discharged home rather than to an institution (66% vs. 44%, P < 0.03). These
      patients with normal serum CRP had higher absolute values for total functional
      independence measures and functional independence measures motor scores on
      admission, as well as on discharge (i.e., less disability). They also had fewer
      infections or other medical complications. However, the absolute magnitude of
      improvement (DeltaFIM) and length of stay were similar in the normal and elevated
      CRP groups. Multivariable logistic regression model did not show serum CRP level
      on admission to predict rehabilitation functional outcomes. CONCLUSIONS: Serum
      CRP level does not predict functional outcome at discharge on inpatient
      rehabilitation for stroke.

PMID- 18716486
TI  - Development of the upper-body dressing scale for a buttoned shirt: a preliminary
      correlational study.
AB  - OBJECTIVES: A patient with poststroke hemiparesis learns to use the nonparetic
      arm to compensate for the weakness of the paretic arm to achieve independence in
      dressing. This is the learning process of new component actions on dressing. The
      purpose of this study was to develop the Upper-Body Dressing Scale (UBDS) for
      buttoned shirt dressing, which evaluates the component actions of upper-body
      dressing, and to provide preliminary data on internal consistency of the UBDS, as
      well as its reproducibility, validity, and sensitivity to clinical change.
      DESIGN: Correlational study of concurrent validity and reliability in which 63
      consecutive stroke patients were enrolled in the study and were assessed
      repeatedly by the UBDS and the dressing item of Functional Independent Measure
      (FIM). RESULTS: Fifty-one patients completed the 3-wk study. The Cronbach's
      coefficient alpha of UBDS was 0.88. The principal component analysis extracted
      two components, which explained 62.3% of total variance. All items of the scale
      had high loading on the first component (0.65-0.83). Actions on the paralytic
      side were the positive loadings and actions on the healthy side were the negative
      loadings on the second component. Intraclass correlation coefficient was 0.87.
      The level of correlation between UBDS score and FIM dressing item scores was 
      0.72. Logistic regression analysis showed that only the score of UBDS on the
      first day of evaluation was a significant independent predictor of dressing
      ability (odds ratio, 0.82; 95% confidence interval, 0.71-0.95). The UBDS scores
      for paralytic hand passed into the sleeve, sleeve pulled up beyond the elbow
      joint, and sleeve pulled up beyond the shoulder joint were worse than the score
      for the other components of the task. These component actions had positive
      loading on the second component, which was identified by the principal component
      analysis. CONCLUSIONS: The UBDS has good internal consistency, reproducibility,
      validity, and sensitivity to clinical changes of patients with poststroke
      hemiparesis. This detailed UBDS assessment enables us to document the most
      difficult stages in dressing and to assess motor and process skills for
      independence of dressing.

PMID- 18716487
TI  - Factors predicting pressure ulcers in veterans with spinal cord injuries.
AB  - OBJECTIVES: To identify patient risk factors for pressure ulcers in a sample of
      veterans with spinal cord injuries and disorders. DESIGN: A survey incorporating
      questions from the Centers for Disease Control and Prevention's Behavioral Risk
      Factor Surveillance System was mailed to individuals with spinal cord injuries
      and disorders in 2003. A multiple logistic regression model including 2574
      respondents was used to examine the association between patient characteristics
      and the self-report of pressure ulcers. RESULTS: Approximately 36% of respondents
      reported having pressure ulcers during the previous year. Respondent
      characteristics significantly associated with report of one or more pressure
      ulcers included diabetes (incidence rate ratio [IRR] = 1.36, P < 0.001), smoking
      (IRR = 1.16, P = 0.030), injury duration >30 yrs (IRR = 1.27, P = 0.000), and
      reporting frequent depressive symptoms (IRR = 1.30, P < 0.001). Veterans who did
      not have injuries related to their military service (IRR = 1.39, P < 0.001) or
      who received care at non-VA facilities in addition to or instead of VA facilities
      (IRR = 1.13, P = 0.024) were more likely than other veterans to report pressure
      ulcers. CONCLUSION: Efforts to prevent pressure ulcers should include increased
      attention to managing diabetes and depressive symptoms. Further research to
      explore the association between multiple healthcare system use and the risk of
      pressure ulcers should be pursued.

PMID- 18716488
TI  - Testosterone levels among men with spinal cord injury: relationship between time
      since injury and laboratory values.
AB  - OBJECTIVES: The objectives of the present study were to determine the prevalence
      of low testosterone among a sample of men with spinal cord injury and to examine
      the relationship among testosterone, time since injury, and select laboratory
      values. DESIGN: Participants were 102 men with spinal cord injury participating
      in inpatient or outpatient rehabilitation. Data included total serum testosterone
      level, demographic and injury information, and laboratory values. RESULTS: Sixty
      percent of men with spinal cord injury had low testosterone levels. The median
      testosterone level for the entire sample was 220 ng/dl (normal reference range =
      241-827 ng/dl). Low testosterone was significantly associated with less time
      since injury, lower hemoglobin, and higher prolactin in the univariate analyses
      at P < 0.05. CONCLUSIONS: The results indicate that men with spinal cord injury
      are at risk for low serum testosterone. Testosterone levels were also related to
      time since injury and hemoglobin and prolactin levels. These findings suggest the
      need for changes to occur in clinical practice. Guidelines are needed for when
      and how often testosterone monitoring should be conducted. Future research should
      address the pathophysiology of low testosterone and the outcomes of testosterone
      treatment.

PMID- 18716489
TI  - Hyperthyroidism as a cause of autonomic dysreflexia.
AB  - A 25-yr-old female tetraplegic patient experienced autonomic dysreflexia episodes
      involving hypertension, headache, facial flushing, and tachycardia. The symptoms
      were not related to the bladder or bowel. The episodes did not seem to be linked
      to any mechanical cause. The patient was incidentally diagnosed with
      hyperthyroidism. Treatment with antithyroid medication resulted in resolution of
      the autonomic dysreflexia. This case suggests that hyperthyroidism may trigger
      autonomic dysreflexia in tetraplegic patients.

PMID- 18716490
TI  - Rucksack-induced plexopathy mimicking a lateral antebrachial cutaneous
      neuropathy.
AB  - A 20-yr-old active duty soldier complained of right lateral forearm numbness that
      began shortly after carrying 100 lbs of equipment (20-lb load-bearing equipment,
      20-lb individual body armor, and 60-lb rucksack) while deployed during Operation
      Iraqi Freedom. Physical examination revealed normal strength but decreased
      sensation over the right lateral forearm, thumb, and index finger. Imaging
      studies were normal. Electrodiagnostic studies revealed an absent right lateral
      antebrachial cutaneous nerve conduction study with abnormal electromyography
      findings in the right deltoid and biceps brachii. He was diagnosed with an upper
      trunk brachial plexopathy. The patient's symptoms gradually resolved with
      conservative treatment. Although rucksack palsies have been previously reported,
      this relatively rare cause of brachial plexus injury has been generally declining
      with the reengineering of more ergonomically favorable rucksacks. It is possible
      that the additional body armor may have contributed.

PMID- 18716491
TI  - Reflections on the outcome of admitting a blind student into medical school.

PMID- 18716493
TI  - Biopsychosocial correlates of adjustment to pain among people with multiple
      sclerosis.
AB  - OBJECTIVES: The objective of this study was to examine the extent to which pain
      related beliefs and coping strategies predicted measures of adjustment to pain
      among people with multiple sclerosis (MS), over and above that accomplished by
      demographic and clinical variables. METHODS: Participants were a community-based
      sample of people with chronic MS-related pain (N=105) who completed postal
      surveys and standardized interviews that included measures of demographic and MS
      related variables, typical pain intensity, psychologic functioning, pain
      interference, pain beliefs, and coping strategies. RESULTS: Pain-specific beliefs
      and coping strategies were associated with and explained a significant proportion
      of the variance in adjustment to pain (24% to 34%) among people with MS, over and
      above that accomplished by demographic and disease-related variables and pain
      intensity. Compatible with previous studies, greater endorsement of pain
      constancy and catastrophizing were significant predictors of poorer adjustment,
      whereas perceived ability to decrease pain and increasing behavioral activities
      in response to pain were related to positive adaptation. DISCUSSION: These
      findings provide support for the premise that psychosocial factors remain central
      in disability-related pain and suggest the possibility that interventions
      targeting these variables would reduce the negative impact of pain among people
      with MS.

PMID- 18716494
TI  - Ketamine and midazolam delivered by patient-controlled analgesia in relieving
      pain associated with burns dressings.
AB  - BACKGROUND: A study involving the use of a mixture of ketamine and midazolam
      delivered via patient-controlled analgesia (PCA) device was trialed to assess its
      effectiveness in reducing pain associated with repeated burns dressings in an
      adult population. METHODS: Patients undergoing burns dressings changes were given
      a PCA device of ketamine and midazolam to use during the procedure. The aims were
      to investigate the efficacy of the device and to ascertain what (if any) adverse
      effects were associated with its use. RESULTS: During the trial period, 44
      patients who underwent 95 separate procedures were enrolled. The effectiveness of
      the device was rated (out of 10) by both staff and patients with the mean scores
      being 8.47 and 8.50, respectively. In all but 1 case, the proposed procedure was
      carried out successfully. Thirteen patients reported a total of 23 adverse
      effects, with hallucinations (11) being the most common. CONCLUSIONS: The use of
      ketamine/midazolam delivered by PCA was shown to be an effective means of pain
      control during burns dressings as assessed by both staff and patients. The
      incidence of adverse events was low.

PMID- 18716495
TI  - Parents' understanding of information regarding their child's postoperative pain
      management.
AB  - OBJECTIVES: Unlike information provided for research, information disclosed to
      patients for treatment or procedures is largely unregulated and, as such, there
      is likely a considerable variability in the type and amount of disclosure. This
      study was designed to examine the nature of information provided to parents
      regarding options for postoperative pain control and their understanding thereof.
      METHODS: One hundred eighty-seven parents of children scheduled to undergo a
      surgical procedure requiring inpatient postoperative pain control completed
      questionnaires that elicited information regarding their perceptions and
      understanding of, and satisfaction with, information regarding postoperative pain
      management. RESULTS: Results showed that there was considerable variability in
      the content and amount of information provided to parents based on the method of
      postoperative pain control provided. Parents whose child received patient
      controlled analgesia were given significantly (P<0.025) more information on the
      risks and benefits compared with those receiving nurse controlled or intravenous
      prn analgesia. Approximately one third of parents had no understanding of the
      risks associated with postoperative pain management. Parents who received pain
      information preoperatively and who were given information regarding the risks and
      benefits had improved understanding compared with parents who received no or
      minimal information (P<0.001). Furthermore, information that was deemed unclear
      or insufficient resulted in decreased parental understanding. DISCUSSION: These
      results demonstrate the variability in the type and amount of information
      provided to parents regarding their child's postoperative pain control and
      reinforce the importance of clear and full disclosure of pain information,
      particularly with respect to the risks and benefits.

PMID- 18716496
TI  - Sex differences in presentation, course, and management of low back pain in
      primary care.
AB  - OBJECTIVE: Epidemiologic surveys frequently show that women more often and are
      more affected by low back pain (LBP). The aim of this secondary analysis of a
      randomized controlled study was to explore whether presentation and course of LBP
      of women is different from men, and if sex affects the use of healthcare services
      for LBP. METHODS: Data from 1342 [778 (58%) women] patients presenting with LBP
      in 116 general practices were collected. Patients completed standardized
      questionnaires before and after consultation and were contacted by phone 4 weeks,
      6 months, and 12 months later for standardized interviews by study nurses.
      Functional capacity was assessed with Hannover Functional Ability Questionnaire
      (HFAQ). Logistic regression models-adjusting for sociodemographic and disease
      related data-were conducted to investigate the effect of sex for the use of
      healthcare services. RESULTS: Women had on average a lower functional capacity at
      baseline and after 12 months. They were more likely to have recurrent or chronic
      LBP and to have a positive depression score. Being female was associated with a
      low functional capacity after 12 months (odds ratio: 1.7, 95% confidence
      interval: 1.2-2.3), but baseline functional capacity, chronicity, and depression
      were stronger predictors. In univariate analysis, women had a tendency of higher
      use of healthcare services. Those differences disappeared after adjustment.
      DISCUSSION: Our findings confirm that women are more severely affected by LBP and
      have a worse prognosis. Utilization of healthcare services cannot be fully
      explained by female sex, but rather by a higher impairment by back pain and pain
      in other parts of the body characteristic of the female population.

PMID- 18716498
TI  - Whiplash (grade II) and cervical radiculopathy share a similar sensory
      presentation: an investigation using quantitative sensory testing.
AB  - OBJECTIVES: Recent research has identified the coexistence of generalized sensory
      hypersensitivity and hypoesthetic changes suggestive of a neuropathic component
      to chronic whiplash associated disorders (WAD). This study aimed to compare
      chronic whiplash with a cervical neuropathic condition-cervical radiculopathy,
      using Quantitative Sensory Testing. METHODS: Fifty participants with chronic
      grade II WAD (>3 mo), 38 participants with radiculopathy, and 31 controls who
      were age and sex matched to participants with WAD participated in the study.
      Quantitative Sensory Testing including detection thresholds (electrical, thermal,
      and vibration) and pain thresholds (pressure, cold) were measured from bilateral
      hand sites corresponding to innervation areas of the lower cervical nerve roots
      and a remote site in the lower limb. RESULTS: The whiplash and cervical
      radiculopathy groups demonstrated lower pain thresholds to both pressure and cold
      stimuli at all sites compared with the controls (P<0.01). The symptomatic limbs
      of the radiculopathy group showed the greatest elevation in detection thresholds
      for all stimuli compared with the asymptomatic limbs of this group, the whiplash
      and control groups (P<0.01). There was no difference in detection thresholds
      between the asymptomatic limbs of the radiculopathy group and the whiplash group
      (P>0.05) but both these groups showed higher detection thresholds than the
      controls (P<0.05). DISCUSSION: Generalized sensory hypersensitivity and
      hypoesthesia occur in both chronic whiplash and cervical radiculopathy. This may
      represent disordered central pain processing but could indicate peripheral nerve
      dysfunction.

PMID- 18716497
TI  - Effect of microneedle design on pain in human volunteers.
AB  - OBJECTIVES: To design microneedles that minimize pain, this study tested the
      hypothesis that microneedles cause significantly less pain than a 26-gauge
      hypodermic needle, and that decreasing microneedle length and the number of
      microneedles reduces pain in normal human volunteers. METHODS: Single
      microneedles with lengths ranging from 480 to 1450 microm, widths from 160 to 465
      microm, thicknesses from 30 to 100 microm, and tip angles from 20 to 90 degrees;
      and arrays containing 5 or 50 microneedles were inserted into the volar forearms
      of 10 healthy, human volunteers in a double-blinded, randomized study. Visual
      analog scale pain scores were recorded and compared with each other and to the
      pain from a 26-gauge hypodermic needle. RESULTS: All microneedles investigated
      were significantly less painful than the hypodermic needle with microneedle pain
      scores varying from 5% to 40% of the hypodermic needle. Microneedle length had
      the strongest effect on pain, where a 3-fold increase in length increased the
      pain score by 7-fold. The number of microneedles also affected the pain score,
      where a 10-fold increase in the number of microneedles increased pain just over 2
      fold. Microneedle tip angle, thickness, and width did not significantly influence
      pain. DISCUSSION: Microneedles are significantly less painful than a 26-gauge
      hypodermic needle over the range of dimensions investigated. Decreasing
      microneedle length and number of microneedles reduces pain.

PMID- 18716499
TI  - Fear-avoidance beliefs, physical activity, and disability in elderly individuals
      with chronic low back pain and healthy controls.
AB  - OBJECTIVE: Research studies focussing on the fear-avoidance beliefs model (FABM)
      have expanded considerably during the last years, however, there has been very
      little research directed at the elderly. The objective of the present study was
      to investigate the validity of the FABM in older patients with chronic low back
      pain (CLBP). METHOD: In a cross-sectional study, a group of elderly patients with
      CLBP (N=103) was compared with an age-matched group of pain-free individuals
      (N=59) to test the constructs inherent in the FABM. Constructs include fear
      avoidance beliefs (FABs), disability, disuse, and physical activity. In addition,
      the relationship of these constructs was also investigated in the patient group.
      CLBP-patients had an average age of 71.41 years (SD=5.2) and pain-free
      individuals of 71.19 years (SD=4.73). Individuals participated in a photographed
      series of physical activities adapted to the age group (Photograph Series of
      Daily Activities-German version for the elderly) for the assessment of FAB, in
      the Hannover Disability Questionnaire, in the Freiburg Physical Activity
      Questionnaire, and in an ultrasound measurement to evaluate lumbar flexion. In
      addition, they completed an activity diary for 1 week. Before computation, the
      physical activity measurements were converted into metabolic units that
      characterize energy expenditure. RESULTS: In the patient group, FAB, pain
      intensity, and age predicted functional capacity, but not physical activity.
      Lumbar flexion was predicted by FAB and age. Patients were more fear-avoidant,
      reported more disability, and displayed less lumbar flexion than the pain-free
      individuals. No differences between the groups could be detected in regard to
      energy expenditure measured either by the questionnaire or by diary data.
      CONCLUSIONS: The findings are consistent with results reported in the literature
      for younger age groups and confirm the assumption that the FABM is also valid for
      the elderly.

PMID- 18716500
TI  - The associations between pain intensity, psychosocial variables, and pain
      duration/recurrence in a large sample of persons with nonspecific spinal pain.
AB  - OBJECTIVES: The aims of this study were: (1) to describe and compare pain
      intensity, disability, cognitive, physical, behavioral, and environmental
      variables in 4 predefined categories, on the basis of duration and recurrence of
      nonspecific spinal pain; and (2) to compare disability, cognitive, physical,
      behavioral, and environmental variables in these 4 predefined categories, after
      controlling for pain intensity. METHODS: Postal questionnaires were sent to a
      random sample of 5000 persons, aged 20 to 50 years, in Sweden. The response rate
      was 39%. One thousand and twenty-four participants reporting spinal pain were
      divided into 4 predefined categories (n=100, 215, 172, and 537) based on duration
      and recurrence of pain. Multivariate analyses of variance and covariance were
      performed to investigate differences between the 4 pain duration/recurrence
      groups. RESULTS: The first analyses revealed that the 4 pain duration/recurrence
      groups differed in pain intensity, disability, 7 cognitive variables, and
      perceived social support. After controlling for pain intensity, small but
      significant group differences were identified in depression, catastrophizing,
      pain expectations, and perceived social support. Higher levels of catastrophizing
      and pain expectations and lower levels of perceived social support were seen in
      groups with longer duration of pain. DISCUSSION: After controlling for pain
      intensity, categories based on pain duration/recurrence differed in 3 cognitive
      variables and perceived social support. Pain expectations, catastrophizing and
      perceived social support were related to longer duration of pain. Between-group
      differences were small and pain duration/recurrence was not an important
      explanatory factor.

PMID- 18716501
TI  - Anxiety, mood, and behavioral disorders among pediatric patients with juvenile
      fibromyalgia syndrome.
AB  - BACKGROUND: Mood and anxiety disorders are common psychiatric conditions among
      adult patients with fibromyalgia syndrome, but little is known about whether
      psychiatric disorders are prevalent among pediatric patients with fibromyalgia.
      OBJECTIVE: The primary objective of this study was to assess the prevalence of
      mood, anxiety, and behavioral disorders in a clinical sample of children and
      adolescents with juvenile primary fibromyalgia syndrome (JPFS) and assess the
      relationship between psychiatric disorders and JPFS symptom severity. METHODS:
      Standardized psychiatric interviews were conducted with children and their
      parents/primary caregivers, and measures of symptom severity including pain
      intensity and physician global ratings were obtained for 76 children and
      adolescents diagnosed with JPFS (ages 11 to 18 y) in pediatric rheumatology
      clinics at 4 hospitals in the Midwest. RESULTS: A total of 67.1% of patients had
      at least 1 current and 71.5% had at least 1 lifetime DSM-IV (Diagnostic and
      Statistical Manual of Mental Disorders-fourth edition) psychiatric diagnosis. The
      most frequent psychiatric diagnosis was anxiety disorder (57.5% of JPFS
      patients). Although mood difficulties were also common, the presence of major
      depression was lower than has been reported for adults with fibromyalgia
      syndrome. Physicians' global assessment of functioning was significantly lower
      for patients with a current anxiety disorder. There were no significant
      differences in pain severity among patients with and without anxiety, mood, or
      behavioral disorders. DISCUSSION: There seems to be a high prevalence of anxiety
      disorders in patients with JPFS, and presence of anxiety disorder is associated
      with poorer physician-rated functioning. Future research should explore whether
      early anxiety symptoms are predictive of long-term functioning.

PMID- 18716502
TI  - Prevalence rates for and predictors of self-reported adherence of oncology
      outpatients with analgesic medications.
AB  - OBJECTIVES: Inadequate adherence with an analgesic regimen may be a reason why
      oncology patients experience unrelieved pain. However, only a limited number of
      studies have evaluated the prevalence rates for adherence and no studies have
      attempted to determine predictors of adherence in patients with cancer pain. On
      the basis of concepts from the Health Belief Model, the purposes of this study
      were to describe oncology outpatients' level of adherence with an analgesic
      regimen and to evaluate the direct and indirect effects of selected demographic
      variables, pain characteristics, barriers to pain management, and self-efficacy
      (SE) on adherence with an analgesic regimen. METHODS: A descriptive, cross
      sectional study recruited outpatients from oncology clinics in a large, tertiary
      referral cancer hospital in Norway. A sample of 174 oncology outpatients
      completed a demographic questionnaire, the Brief Pain Inventory, 2 self-reported
      adherence measures, the Barriers Questionnaire, and a SE questionnaire. RESULTS:
      Only 41% of the patients were adherent with their analgesic regimen. In the
      regression analysis, 29.9% of the variance in adherence was explained. Higher
      adherence scores were associated with male sex, and also lower SE for physical
      function scores, higher average pain intensity scores, higher pain relief scores,
      and the use of strong opioid analgesics. CONCLUSIONS: Improvements in pain
      management may occur if clinicians routinely assessed patients' level of
      adherence with their analgesics regimen.

PMID- 18716503
TI  - Complex regional pain syndrome (type 1): a comparison of 2 diagnostic criteria
      methods.
AB  - BACKGROUND: Complex regional pain syndrome (CRPS) is a common problem presenting
      to orthopedic surgeons or pain therapists, most frequently encountered after
      trauma or surgery to a limb. Because of a lack of a simple objective diagnostic
      test, diagnosis is reliant on clinical assessment. Prospective studies have
      repeatedly demonstrated a higher incidence than retrospective studies, an
      observation that has been challenged owing to the lack of uniformity of
      diagnostic criteria across specialties and workers researching the condition.
      METHODS: A series of 262 adult patients presenting to the Bristol Royal Infirmary
      with a closed unilateral distal radial fracture were assessed at a mean of 9.47
      weeks after their injury by a single clinician (J.A.L.). Each assessment made
      allowed comparison of the modified International Association for the Study of
      Pain (Bruehl) criteria for the presence of CRPS with the criteria described by
      Atkins. FINDINGS: The incidence of CRPS was similar using either criteria (Bruehl
      20.61% vs. Atkins 22.52%). Using the Bruehl criteria as a gold standard, there
      was strong diagnostic agreement (kappa=0.79, sensitivity=0.87, specificity=0.94).
      Disagreements between the 2 criteria methods were found in 19 patients. The
      majority of these discordances were due to differences in pain and sensory
      abnormality assessment. INTERPRETATION: These findings show that the Bruehl and
      Atkins criteria are basically concordant. The differences reflect only minor
      variations in the assessment of pain. Agreement between researchers in the
      orthopedic and pain therapy communities will allow improved understanding of
      CRPS.

PMID- 18716504
TI  - Anterolateral percutaneous vertebroplasty at C2 for lung cancer metastasis and
      upper cervical facet joint block.
AB  - Percutaneous vertebroplasty (PVP) of the axis (C2) is less aggressive than any
      surgical stabilizing procedure for the upper cervical spine, and it does not
      restrict the mobility of the upper cervical joints. Disruption of the weight
      bearing unit of the second cervical (C2) vertebral body causes excessive load at
      the relatively small adjacent upper cervical joints. Upper cervical joint block
      before or after PVP at the C2 level has not been reported thus far. A 67-year-old
      man was referred to a pain clinic with a 6-month history of increasing neck pain
      without focal neurologic symptoms. Studies revealed a compression fracture of the
      C2 vertebral body and invasion of the adjacent soft tissue. To treat the
      mechanical component of the symptoms, anterolateral PVP at C2 was successfully
      performed, but the residual suboccipital headache was alleviated only after upper
      cervical joint block was performed. Thus, upper cervical joint block can be
      performed to treat the residual suboccipital headache after PVP at C2.

PMID- 18716505
TI  - Neuropathic pain and foot drop related to nerve injury after short duration
      surgery and caudal analgesia.
AB  - Caudal anesthesia is the most common type of regional anesthetic technique
      performed in children. The incidence of neurologic adverse events is extremely
      rare. A postoperative complication of a mild but permanent neurologic deficit
      after administration of a caudal anesthetic in a previously well 9-year-old boy
      who required emergency scrotal exploration for a testicular torsion is reported.
      The caudal injection provided good postoperative analgesia, which probably
      resulted in the patient remaining in the same position overnight. This may have
      contributed to the development of the neurologic deficit, probably owing to a
      compressive neuropathy. We suggest that, as anesthesiologists obtaining informed
      consent for anesthetic interventions, we now need to inform guardians/carers of
      pediatric patients who are to receive caudal analgesia of the extremely small
      material risk of neurologic damage after caudal anesthesia. Additionally, the
      anesthetic community may need to consider revising postoperative care
      instructions to prevent the future occurrence of this rare outcome, particularly
      if using additives that prolong analgesic block duration.

PMID- 18716506
TI  - Multiple pheochromocytomas in a patient with blurred vision.
AB  - We report on a 19-year-old male diagnosed with multiple pheochromocytomas after
      an I-123 metaiodobenzylguanidine (MIBG) scan. Multiple imaging was obtained
      because of concern for von Hippel-Lindau disease (VHL) after bilateral retinal
      angiomas were discovered on ophthalmologic consultation as a follow-up from the
      Emergency Department. Computed tomography (CT) and magnetic resonance imaging
      (MRI) were able to localize the adrenal and extra-adrenal tumors; however,
      accurate differentiation between pheochromocytomas and other adrenal tumors was
      not possible. I-123 MIBG is the test of choice for evaluating functionality and
      location of pheochromocytomas because of its high sensitivity and specificity. I
      123 MIBG was performed before surgery to confirm that the lesions were indeed
      pheochromocytomas and also to rule out metastatic disease. He was started on
      alpha- and beta-blocker medication for at least 3 weeks, followed by surgery. The
      postoperative period was uneventful. DNA testing was performed and revealed
      mutations in the VHL gene previously reported to be associated with von Hippel
      Lindau syndrome type II and genetic counseling was recommended. He was presented
      in urology tumor board conference with recommendations for follow-up CT and
      laboratory tests after 3 months. Otherwise, the patient is doing well and
      asymptomatic at this time.

PMID- 18716507
TI  - Intermittent FDG uptake in lipomatous hypertrophy of the interatrial septum on
      serial PET/CT scans.
AB  - We present a unique case of a patient with a clinical history of distal
      esophageal carcinoma and CT appearance of lipomatous hypertrophy of the
      interatrial septum who displayed fluorine-18-fluorodeoxyglucose (FDG) uptake in
      the interatrial septal fat on only the second of 4 serial PET/CT studies. As
      PET/CT scans are used for the initial staging of esophageal carcinoma, one should
      not mistake more benign causes of mediastinal uptake for metastasis when
      observing an intermittent pattern of uptake on a PET/CT scan.

PMID- 18716508
TI  - Ventilation-perfusion scintigraphy in children and adolescents is associated with
      a low rate of indeterminate studies.
AB  - BACKGROUND: In selected populations, ventilation-perfusion (V/Q) studies are
      nearly as accurate as CT angiography (CTA) for the diagnosis of pulmonary emboli
      (PE). This study was performed to determine the percentage of V/Q studies in
      children and adolescents that are indeterminate for the presence of PE. MATERIALS
      AND METHODS: V/Q studies performed over a period of 2 years were reviewed.
      Studies from children and adolescents with chronic lung disease or recent
      documented severe PE were excluded. There were 37 V/Q studies and 3 perfusion
      only (Q) studies in 35 patients. Studies were evaluated using modified Biello
      criteria. Effective doses (EDs) for V/Q and CTA studies of the lung were
      calculated from administered activities and CT exposure parameters used. RESULTS:
      Eighteen studies were normal, 4 studies had a very low probability of PE, 6 were
      low probability, and 2 were high probability for PE. Four studies were negative
      for new PE when compared with a previous study. Five V/Q studies and 1 Q only
      study were indeterminate for PE (15%), only slightly higher than the reported
      percentage of indeterminate CTA in adults. ED from V/Q was about half the ED from
      CT angiography. Breast dose from V/Q was less than 3% of the breast dose from CT.
      CONCLUSION: In this selected group of children and adolescents, the percentage of
      indeterminate V/Q studies is low. V/Q has considerably lower absorbed breast and
      effective radiation doses than CTA, and is still appropriate for imaging children
      who are suspected of having PE.

PMID- 18716509
TI  - PET/CT in the evaluation of lymphoma in patients with HIV-1 with suppressed viral
      loads.
AB  - OBJECTIVE: Positron emission tomography (PET) with F-18 fluorodeoxyglucose
      detects active lymphoid tissue during HIV-1 infection, with distinct patterns of
      lymphoid activation correlating to various stages of disease activity. Patients
      with HIV-1 are at risk for lymphoma, making the differential diagnosis between
      benign and malignant lymphadenopathy imperative. This study retrospectively
      evaluated the role of PET/computed tomography (CT) in differentiating active
      lymphoma from persistent generalized lymphadenopathy in patients with HIV-1.
      MATERIALS AND METHODS: Seven patients with HIV-1 underwent PET/CT. Six, with
      known non-Hodgkin lymphoma underwent a total of 16 PET/CT scans; 5/16 scans were
      performed for initial staging, and 10/16 for evaluating treatment response and
      follow-up. One patient was referred for evaluation of lymphadenopathy suspected
      of being lymphoma. PET/CT findings were compared with concurrent clinical,
      immunologic, and virological data. RESULTS: PET/CT accurately depicted the extent
      of lymphoma in 12/16 patients' scans (75%), yet in 4/16 (25%) scans increased
      fluorodeoxyglucose uptake was noted in lymph nodes of normal CT appearance
      (PET+/CT-). Viral loads ranged from 0 to 84,000 copies/mL, CD4 T-cell count
      ranged from 130 to 474 cells/muL in the group. The highest values of both
      laboratory parameters were concurrent with the discrepant PET+/CT- scans, seen in
      4 scans, in 2 patients. The PET+/CT- findings in both these patients were
      observed in neck, axillae, mediastinum, spleen, and inguinal regions, and sample
      biopsies of the PET (+) nodes consequently proved benign findings in both
      patients. All PET+/CT+ findings correctly indicated lymphoma status, as proven by
      clinical follow-up. CONCLUSION: PET/CT accurately detected lymphoma in patients
      with HIV-1 and had been used confidently as a management tool in this patient
      group. In the context of discrepant PET/CT findings, increased viral loads and
      CD4 levels may imply benign HIV-related lymphadenopathy.

PMID- 18716510
TI  - Tc-99m MIBI scintigraphy in tall cell variant of papillary thyroid carcinoma with
      negative radioiodine scan.
AB  - We report on a 45-year-old man who had a mass on the wall of the anterior right
      hemithorax. An excisional biopsy indicated carcinoma metastasis from thyroid
      malignancy. Tc-99m methoxyisobutyl isonitrile (MIBI) scintigraphy revealed
      markedly increased activity on the left side of the thyroid and the thoracic wall
      mass. Postoperative histology revealed a tall cell variant of papillary thyroid
      carcinoma. Whole body scintigraphy after radioiodine treatment was negative
      twice. However, Tc-99m MIBI and bone scintigraphy showed multiple soft tissue and
      bone metastases in the follow-up period. He died 3 years later because of
      complications of distant lung metastases.

PMID- 18716511
TI  - PET/CT examination in an anaplastic malignant lymphoma with extensive reactive
      involvement.

PMID- 18716512
TI  - Unusual abdominal localization of cat scratch disease mimicking malignancy on F
      18 FDG PET/CT examination.

PMID- 18716513
TI  - Elevated FDG uptake in Kaposi sarcoma mimicking Hodgkin's lymphoma relapse.

PMID- 18716514
TI  - Unusual increased metaiodobenzylguanidine uptake in liposarcoma.

PMID- 18716515
TI  - Male primary breast cancer found on FDG-PET/CT.

PMID- 18716516
TI  - F-18 FDG PET imaging of fibrolamellar hepatocellular carcinoma.

PMID- 18716517
TI  - Serial PET scans demonstrate the success and limitations of antiangiogenic
      treatment in a case of lung adenocarcinoma.

PMID- 18716518
TI  - Asymmetric I-131 uptake in the submandibular gland in the setting of thyroid
      carcinoma.

PMID- 18716519
TI  - Gastric cancer found on 3'-deoxy-3' F-18 fluorothymidine positron emission
      tomography.

PMID- 18716520
TI  - F-18 fluorodeoxyglucose uptake in gastric adenoma after stomach distention by
      water.

PMID- 18716521
TI  - F-18-FDG-PET/CT imaging of small cell carcinoma of the colon.

PMID- 18716522
TI  - Subclavian vein stenosis detected with a gastrointestinal bleeding scan.

PMID- 18716523
TI  - Benign F-18 FDG uptake along a mediastinoscopy tract: demonstration by F-18 FDG
      PET/CT imaging.

PMID- 18716524
TI  - Increased F-18 FDG uptake in resolving atraumatic bilateral adrenal hemorrhage
      (hematoma) on PET/CT.

PMID- 18716525
TI  - Tc-99m MDP uptake resulting from right internal carotid artery occlusion of
      Moyamoya disease.

PMID- 18716526
TI  - Current readings.

PMID- 18716528
TI  - The effects of different abdominal pressures on pulmonary function test results
      in laparoscopic cholecystectomy.
AB  - This study aimed to examine the effects of differing intra-abdominal pressures on
      pulmonary function test results in laparoscopic cholecystectomy. Forty-five
      patients were operated on under 3 different intra-abdominal pressures: group A (8
      mm Hg), group B (12 mm Hg), and group C (15 mm Hg). On the first day before and
      after the operation, forced vital capacity (FVC), forced expiratory volume in the
      first second (FEV1), FEV1/FVC rate, peak expiratory flow speed (PEF), and maximal
      middle expiration speed (FEF25-75) values were measured using Vmax 229
      spirometry. No significant differences were observed among the 3 groups regarding
      preoperative and postoperative FVC, FEV1, FEV1/FVC, PEF, and FEF25-75 values
      (P=0.96, P=0.73, P=0.48, P=0.34, and P=0.33, respectively). When the groups'
      preoperative and postoperative values were compared, FVC, FEV1, and PEF values
      significantly decreased in each group. The FEF25-75 values statistically
      significantly decreased in groups B and C when compared with their preoperative
      values; however, the decrease in group A was not significant. In conclusion,
      different intra-abdominal pressures during laparoscopic cholecystectomy had
      similar effects on pulmonary function test results. However, lower intra
      abdominal pressures were associated with slightly more negative effects on FEF25
      75 values.

PMID- 18716529
TI  - Laparoscopic cholecystectomy for acute cholecystitis in the elderly: is it safe?
AB  - BACKGROUND: The purpose of this study was to evaluate the outcome of laparoscopic
      cholecystectomy (LC) in patients with acute cholecystitis aged 75 years and
      older. MATERIALS AND METHODS: A retrospective chart review was performed on the
      1216 cholecystectomies performed in our department from 2000 to 2005. A total of
      225 patients underwent attempted LC for acute cholecystitis, of whom 42 were more
      than 75 years old and 183 younger. RESULTS: There was no difference in mean
      duration of symptoms before admission and length of hospital stay before surgery
      (3.8 d in elderly vs. 3.1 in younger patients, and 2.8 vs. 2.3 d, respectively).
      In all, 21% of the elderly patients had American Society of Anesthesiologists
      score III and IV. Mean operative time and conversion rate to open surgery were
      similar in both groups. Postoperative stay was longer in elderly (3.9 vs. 2.8).
      The postoperative complications rate and mortality were significantly higher in
      the elderly group (31% vs. 15%, and 4.8% vs. 0.5%, respectively). CONCLUSIONS: LC
      in elderly patients suffering from acute cholecystitis is feasible and effective.
      It is associated with a higher rate of morbidity unrelated to the surgical site
      and mortality in elderly compared with younger patients. Stronger selection of
      elderly patients for surgery is needed.

PMID- 18716530
TI  - Laparoscopic distal pancreatectomy and open distal pancreatectomy: a
      nonrandomized comparative study.
AB  - Although laparoscopic distal pancreatectomy (LDP) is technically feasible, its
      benefits remain uncertain. The purpose of this study was to compare the clinical
      results of LDP and open distal pancreatectomy (ODP). The medical records of 14
      consecutive patients who underwent LDP were reviewed and compared with those of
      19 patients who underwent ODP. All patients were treated for benign or borderline
      malignant disease of the pancreas. Operation time was longer for LDP than for ODP
      (290.7 vs. 213.8 min, P=0.0022), and postoperative analgesics were administered
      less frequently for patients who underwent LDP. Patients treated by LDP had
      earlier recovery of bowel function, shorter time to oral intake, and shorter
      postoperative hospital stay than those treated by ODP. No difference in morbidity
      or inflammatory response was observed between the 2 groups. LDP for benign or
      borderline malignant disease of the pancreas provides benefits without increasing
      morbidity.

PMID- 18716531
TI  - Is local anesthesia or oral analgesics necessary after mini-laparoscopic
      functional surgery in children and young adults?: A prospective randomized trial.
AB  - BACKGROUND: This prospective, randomized, single-blind trial was to determine if
      local anesthesia or oral analgesics reduce postoperative pain after mini
      laparoscopic functional surgery. METHODS: One hundred fifteen patients who
      underwent mini-laparoscopic herniorrhaphy or varicocelectomy were assigned
      randomly to receive wound infiltration with xylocaine, regular oral analgesics,
      or a placebo after the procedures. Visual analog pain scores owing to carbon
      dioxide irritation and trocar wounds were recorded 2 hours, 1 day, and 1 week
      after surgery. Levels of pain were measured by a visual analog pain scale.
      Patients' age, type of procedure, pressure of gas insufflated, length of
      procedure, dosage of oral/parenteral analgesics, and trocar-related complications
      were evaluated. RESULTS: There were no significant differences between groups in
      the mean pain scores over trocar wounds 2 hours, 1 day, and 1 week after mini
      laparoscopic procedures, respectively. There were no significant differences
      between groups in satisfaction of pain control regimens. Patients who received
      local anesthesia required fewer on demand meperidine injections than others.
      CONCLUSIONS: Local anesthesia and routine oral analgesic did not significantly
      reduce postoperative pain after mini-laparoscopic surgeries in children and young
      adults.

PMID- 18716532
TI  - Application of a solid tumor model to evaluate tumor recurrence after an open or
      laparoscopic rectal resection in rats.
AB  - PURPOSE: We used a solid tumor model to evaluate the influence of laparotomy
      versus laparoscopy on tumor growth after curative resection for rectal cancer in
      rats. METHODS: Colon tumor cells (DHD/K12/TRb) were administered
      intraperitoneally in 15 rats, which were used as solid tumor donors. Twenty-one
      days later, a 20-mg piece was then implanted in the rectal submucosa of the study
      rats (n=45). Animals were randomized into 3 groups for rectal resection either
      open or laparoscopic using either carbon dioxide (CO2) or helium for
      pneumoperitoneum. Autopsy took place 21 days after resection and tumor recurrence
      was evaluated. RESULTS: Port-site metastasis was observed after laparoscopy with
      CO2 (1 animal) and helium (1), whereas intraperitoneal tumor growth was detected
      in 2 and 3 animals of these groups. No tumor recurrence was observed after open
      surgery. CONCLUSIONS: Our solid tumor model is a novel neoplastic model that
      might simulate the clinical situation of an upper rectal carcinoma. It might be
      helpful to develop new protocols in studying solid tumor biology and different
      surgical procedures for cancer to address problematic issues in oncologic
      research.

PMID- 18716533
TI  - Adoption of self-expanding metallic stents in the palliative treatment of
      obstructive colorectal cancer-look out for perforations!
AB  - Self-expanding metallic stents (SEMSs) are increasingly used for the palliative
      treatment of inoperable colorectal cancer. The aim of the current study was to
      analyze the safety and efficacy of SEMS in the palliative treatment of
      obstructive colorectal cancer. Between 2003 and 2006, SEMS placement was
      attempted in 26 patients suffering from inoperable obstructive colorectal cancer.
      The recovery of the patients and the outcome of this treatment modality were
      analyzed prospectively. SEMS was successfully inserted in 19 (73%) of 26
      patients. In 16 (84%) of these 19 cases, the placement of SEMS was the definitive
      treatment of colorectal obstruction and no additional surgical palliation was
      needed. There were 3 (16%) colonic perforations related to stent application.
      SEMS insertion seems to be an effective alternative in the palliative treatment
      of patients with malignant colorectal obstruction. However, perforation is a
      dangerous complication of the procedure.

PMID- 18716534
TI  - Laparoscopic 3-step restorative proctocolectomy: comparative study with open
      approach in 45 patients.
AB  - BACKGROUND: To compare the results of a total laparoscopic versus open approach 3
      time ileal pouch anal anastomosis (IPAA) for patients with acute or severe
      colitis complicating inflammatory bowel disease. METHODS: Consecutive subtotal
      colectomy was followed by IPAA then by stoma closure. Between 2000 and 2006, 23
      consecutive patients, operated through a total laparoscopic approach were well
      matched with 22 patients operated by open approach. RESULTS: Overall major
      complications rate was lower after laparoscopic than after open approach (5/23
      vs. 9/22; NS). Mean hospital stay for the 3 consecutive procedures was
      significantly reduced after laparoscopic versus open approach (27+/-7 d vs. 39+/
      27 d; P<0.05). CONCLUSIONS: Our case-control study suggests that, in experienced
      centers, a total laparoscopic approach can be viewed as a viable alternative to
      conventional open 3-step IPAA for the treatment of acute or severe colitis
      complicating inflammatory bowel disease.

PMID- 18716535
TI  - Laparoscopic inguinal ligament tenotomy and mesh reinforcement of the anterior
      abdominal wall: a new approach for the management of chronic groin pain.
AB  - BACKGROUND: Chronic groin pain has an incidence of up to 6.2% and is common in
      people undertaking regular sports activity. A variety of surgical options exist
      for unresolving pain, which consist, for the most part, of a repair of the
      posterior abdominal wall, with or without mesh placement. We describe a new
      technique, which combines laparoscopic inguinal ligament tenotomy in conjunction
      with a mesh repair. METHODS: A retrospective analysis of the notes of 48 patients
      was undertaken in conjunction with a mailed questionnaire. Success of surgery was
      judged on return to preinjury sporting activity, severity of pain scores,
      frequency of pain scores, and functional limitation scores. RESULTS: There were
      no major complications associated with the procedure. Severity of pain, frequency
      of pain, and functional limitation scores were all significantly improved after
      surgery (P=0.0012, <0.0001, and <0.0001, respectively). Ninety-two percent of
      patients polled returned to normal sports activity after their surgery (n=24).
      The median return to strenuous sports activity was 28 days (range of 14 to 40 d).
      CONCLUSIONS: The success rates of laparoscopic tenotomy and mesh repair are
      comparable with the published literature and a lower median time interval before
      returning to preinjury sporting activity.

PMID- 18716536
TI  - Totally laparoscopic radical BII gastrectomy for the treatment of gastric cancer:
      a comparison with open surgery.
AB  - BACKGROUND: Laparoscopically assisted distal gastrectomy has been used for distal
      part early gastric cancer resection. However, use of totally laparoscopic gastric
      cancer resection remains limited because of technical problems, especially when
      standard D2 nodal dissection was applied. We had reported the first totally
      laparoscopic Billroth II (BII) subtotal gastrectomy with lymphadenectomy for
      early gastric cancer in the year 1998. The aim of this study is to determine
      whether this procedure is superior to conventional open technique. METHODS: The
      clinical course of 34 consecutive patients who underwent totally laparoscopic BII
      gastrectomy using an upper to lower, right to left, and clockwise quadrant-to
      quadrant technique was compared with 34 sex-matched and age-matched patients who
      underwent open gastrectomy. Main outcome measures included operative time, blood
      loss, length of stay, morbidity and mortality, adequacy of lymphadenectomy, and
      long-term outcome. RESULTS: In the laparoscopic group, all the operations were
      completed by laparoscopic technique, but 1 patient required secondary laparotomy
      for total gastrectomy owing to inadequate resection margin. There was no
      operation mortality in this study. The postoperative complication rates were
      similar in these 2 groups. The mean operative time for laparoscopic group was
      283+/-122 minutes (range: 186 to 480 min), significantly longer than the 195+/-26
      minutes in the conventional group (P<0.001). Laparoscopic group was associated
      with less intraoperative blood loss (74 vs. 190 mL; P<0.01), early flatus passage
      (2.9 vs. 4.9 d; P<0.01), less usage of analgesics (3.5 vs. 5.8 doses; P<0.05),
      and a shorter postoperative hospital stay (8.5 vs. 12.1 d; P<0.01). There was no
      significant difference between laparoscopic and conventional open radical
      gastrectomy with regard to ratio of free margin, number of harvested lymph nodes,
      and survival. CONCLUSION: Although totally laparoscopic BII gastrectomy using the
      upper to lower technique required a longer surgical time and was technically more
      demanding than conventional open surgery, it resulted in shorter recovery time,
      less analgesic use, and less severe physical discomfort without compromising the
      operative curability and oncologic outcomes.

PMID- 18716537
TI  - Transanal circular stapler technique: a simple and highly effective method for
      the management of high-grade stenosis of low colorectal anastomoses.
AB  - Anastomotic stricture is a severe complication of colorectal anastomoses.
      Although dilatation is the treatment of choice for low-grade stenoses, surgery
      may be required for patients with high-grade stenoses or when dilatations fail.
      Surgical repair of colorectal anastomoses is a challenge for the surgeon. The
      transanal circular stapler technique is a simple and effective method for the
      repair of stenoses of low colorectal anastomoses, which avoids extensive tissue
      dissection and achieves excellent long-term results. We present 2 patients
      successfully treated by this technique [in one, the combined (transanal plus
      transabdominal) approach was used] and the relevant literature is briefly
      reviewed.

PMID- 18716538
TI  - Laparoscopic repair of renal artery aneurysm: a description of the technique and
      results in 2 cases.
AB  - BACKGROUND AND PURPOSE: Renal artery aneurysm is a rare occurrence. We report our
      experience in the management of 2 symptomatic renal artery aneurysms with
      laparoscopic approach. MATERIAL AND METHODS: Two patients, male and female, mean
      age 44 years (range: 43 to 45 y), diagnosed with left renal artery aneurysms
      during routine hypertension work-up, underwent laparoscopic aneurysm
      reconstruction. RESULTS: Operative time was 180 and 150 minutes with a warm
      ischemia time of 46 and 15 minutes and an estimated operative bleeding of 50 and
      0 mL, respectively. The patients were discharged home on postoperative day 2 and
      5, respectively. A selective left renal arteriography showed normal caliber of
      the repaired arteries in both patients. A follow-up of 45 and 7 months,
      respectively, has been uneventful. CONCLUSIONS: In well-selected patients,
      vascular surgical techniques may offer excellent results. Laparoscopy provides
      the advantages of the minimally invasive approach while achieving adequate
      vascular control. However, advance training in laparoscopic reconstructive
      surgical techniques is required before attempting this procedure.

PMID- 18716539
TI  - Comparison of safety and efficacy of ultrasonic and bipolar thermal energy: an
      experimental study.
AB  - The safety and efficacy of the Ligasure-8 Generator with the new Ligasure V 5-mm
      forceps (Valleylab, Tyco Healthcare) (LS) and the Ultracision Harmonic Scalpel
      Generator 300 with the new 5 mm 36p Harmonic Ace forceps (Ethicon Endo-Surgery
      ING) (UC) are compared. Twenty New Zealand rabbits were randomly allocated into 2
      groups and the short gastric vessels were divided with either LS or UC. The speed
      of each method, the number of the times it had to be applied, gastric perforation
      rates and histopathologic findings were recorded. Approximately the same number
      of applications was necessary for the 2 groups. UC was significantly faster but
      resulted in contained perforation in 3 cases against 1 for LS (difference
      statistically not significant). A tendency for deeper and more severe
      histopathologic damages was seen with UC. For routine fast dissection, UC is
      satisfactory, but where prevention of thermal injury is important, LS may be more
      appropriate.

PMID- 18716540
TI  - Irrigation eliminates smoke formation in laser laparoscopic surgery: ex vivo
      results.
AB  - BACKGROUNDS AND OBJECTIVES: To evaluate the desmoke effects of irrigation on
      surgical smoke generated during laser laparoscopic surgery using ex vivo model.
      STUDY DESIGN/MATERIALS AND METHODS: A hand-piece was devised as both an
      irrigation tube and a laser fiber holder. The laser system used was a diode
      pumped continuous wave Thulium YAG laser (Lisa laser products OHG, Katlenburg
      Lindau, Germany) emitting at 2.01-mum through a quartz fiber with a core diameter
      of 365 mum. Using a transparent container as experimental model (approximately 3
      L in volume), 6 irrigation rates (0, 20, 40, 60, 80, and 100 mL/min) were tested
      combining with 4 laser power settings (20, 30, 40, and 50 W). To evaluate the
      desmoke efficiency of irrigation, lasing time with effective visibility under
      different combination of irrigation rates and laser powers were documented, and
      corresponding smoke generation rate were calculated (=3 L/lasing time). Analysis
      of variance was used to compare difference and significance was indicated at
      P<0.05. RESULTS: Calculated smoke generation rate was increased with laser power
      whereas decreased with irrigation rate. At 4 tested laser powers, calculated
      smoke generation rates were high (mean: 91.4 to 306.6 mL/s) when no water
      presented, but were significantly decreased (mean: 12.6 to 55.0 mL/s, P<0.001)
      with the lowest water flow rate (20 mL/min) and further decreased with higher
      rates. The proper range of irrigation rate for future clinical practice would be
      around 40 mL/min. CONCLUSIONS: Irrigation eliminates smoke formation accompanying
      laser tissue irradiation. It shows promise for future application in laser
      laparoscopic surgery.

PMID- 18716541
TI  - Death during laparoscopy: can 1 gas push out another? Danger of argon
      electrocoagulation.
AB  - We report the death of a young man during a laparoscopic partial splenectomy
      performed with an argon plasma coagulator to remove a benign cyst. The report
      analyzes the very particular mechanism of a gas embolism, which caused death
      here. This analysis leads us to recommend a close attention on the use of argon
      coagulators during laparoscopy. The aim of this article is to draw surgeons'
      attention to the conclusions of a court-ordered expert assessment intended to
      elucidate the mechanisms responsible for the death of a 20-year-old man during a
      laparoscopic partial splenectomy performed with an argon plasma coagulator to
      remove a benign cyst.

PMID- 18716542
TI  - Massive bleeding from a rectal dieulafoy lesion: combined multidetector-row CT
      diagnosis and endoscopic therapy.
AB  - Dieulafoy lesion is an uncommon cause of acute gastrointestinal bleeding. The
      diagnosis is usually carried out endoscopically. We report a 77-year-old woman
      with rectal Dieulafoy lesion. A recent endoscopic examination missed the lesion
      because it was small and the bleeding was intermittent. In our case, prompt
      colonoscopic therapy was allowed after locating the bleeder by multidetector-row
      computed tomography. On the basis of the success of this procedure, we suggest
      that an emergent multidetector-row computed tomography could have a role in the
      management of patients with massive lower gastrointestinal bleeding.

PMID- 18716543
TI  - Hepaticojejunostomy by interventional radiology with an expandable metallic stent
      after extended right hepatectomy for hilar cholangiocarcinoma: case report.
AB  - As a rare complication of extended right hepatectomy with portal vein resection,
      we were unable to find the cut end of the bile duct of the lateral segment to
      create a hepaticojejunostomy in a 57-year-old man with hilar cholangiocarcinoma.
      However, we succeeded in safely creating a hepaticojejunostomy between the bile
      duct of the lateral segment and a Roux-en-Y jejunum by using the guide wire
      technique and an expandable metallic stent under fluoroscopic and cholangioscopic
      guidance after the operation. The patient was discharged with an internal biliary
      drainage tube, but died of recurrence about 2 years after the operation with the
      hepaticojejunostomy remaining patent.

PMID- 18716544
TI  - Completed laparoscopic pancreaticoduodenectomy.
AB  - A 55-year-old male patient, complaining of skin and sclera yellowing, came in for
      clinical investigation. After complete evaluation, the primitive diagnosis of
      periampullary carcinoma was made and radical surgical resection was planned to be
      performed. Later, a complete laparoscopic pancreaticoduodenectomy was performed
      successfully. The mean operating time was 510 minutes. The intraoperative blood
      loss was 800 mL without intraoperative blood transfusion. No complication was
      noticed. The length of postoperative hospital stay was 14 days. Pathologic
      examination showed well-differentiated adenocarcinoma of common bile duct. The
      patient has been followed-up for 23 months. He is living very well and is capable
      of carrying on daily routine without any evidence of tumor recurrence. Despite
      long operating time, complete laparoscopic pancreaticoduodenectomy is feasible.
      To develop this procedure as more clinical application, some special instruments
      or new technique for laparoscopic intracorporal biliojejunostomy or
      pancreatojejunostomy should be evolved, and a large number of clinical trials are
      also needed to prove its feasibility.

PMID- 18716545
TI  - Colosigmoid adenocarcinoma anastomotic recurrence seeding into a transsphincteric
      fistula-in-ano: a clinical report and literature review.
AB  - We describe the case of a left colon adenocarcinoma anastomotic recurrence that
      metastasized to a benign transsphincteric fistula-in-ano, presumably through the
      implantation of viable malignant cells shed from the secondary tumor, and discuss
      the implications of these findings in colorectal cancer surgery.

PMID- 18716546
TI  - Incarcerated femoral Littre's hernia-transperitoneal preperitoneal hernia repair
      (TAPP) and laparoscopic resection of the necrotic diverticulum.
AB  - Littre's hernias in the region of a femoral hernial orifice have been described
      in numerous cases in the literature. Open inguinal or femoral access was selected
      for all surgical procedures. We are describing the first case of an incarcerated
      Littre's hernia in the region of a femoral hernial orifice treated by means of
      transperitoneal preperitoneal hernia repair with simultaneous laparoscopic
      resection of the diverticulum. On the basis of the example, it is shown that the
      laparoscopic procedure is safe and efficient when performed by an experienced
      laparoscopic surgeon, even for treating incarcerated hernias, including the
      resection of necrotic tissue.

PMID- 18716547
TI  - Simultaneous laparoscopic totally extraperitoneal repair for concurrent
      ipsilateral spigelian and indirect inguinal hernia.
AB  - Simultaneous unilateral spigelian and inguinal hernia is uncommon. Majority of
      the approaches to repair of spigelian hernia is open surgery. We report our
      technique of a simultaneous repair of both spigelian and inguinal hernia using
      the totally extraperitoneal laparoscopic mesh repair.

PMID- 18716548
TI  - A strangulated internal hernia behind the external iliac artery after a
      laparoscopic pelvic lymphadenectomy.
AB  - An internal hernia associated with intra-abdominal blood vessels after a pelvic
      lymphadenectomy is very rare; to our knowledge, only 1 case has been reported to
      date. We report a case of a strangulated internal hernia of the small bowel
      behind the external iliac artery that occurred 3 months after a laparoscopic
      pelvic lymphadenectomy in a patient with cervical cancer. Retroperitonealization
      after the pelvic lymphadenectomy should be considered in patients with tortuous,
      elongated external iliac arteries that could be causal lesions of an internal
      hernia.

PMID- 18716549
TI  - Laparoscopic removal of an intravesical foreign body after laparoscopically
      assisted vaginal hysterectomy: a case report and review of the literatures.
AB  - A foreign body in the bladder is a rare occurrence. Although most intravesical
      foreign bodies can be removed successfully using endoscopic transurethral
      extraction, suprapubic cystotomy may be required for the removal of large bodies.
      We report a case of an intravesical mass 8 cm in diameter that was successfully
      removed using laparoscopic cystotomy without further complications. The foreign
      body was a leiomyoma of the uterus that had not been removed during
      laparoscopically assisted vaginal hysterectomy. The myoma entered into the
      bladder through a defect that was not diagnosed nor repaired until after the
      vaginal extraction portion of the laparoscopically assisted vaginal hysterectomy.
      Laparoscopic removal of intravesical foreign bodies is desirable because it can
      shorten the duration of postoperative recovery, decrease morbidity, and reduce
      the incidence of postoperative complications. Laparoscopy is a useful modality
      for resolving complications within the urinary bladder.

PMID- 18716550
TI  - Preservation of ovarian function in young woman with hodgkin disease by
      laparoscopic medial transposition before abdominal irradiation.
AB  - A case of retro-uterine bilateral ovarian medial transposition in a 24-year-old
      women with Hodgkin's IIIB disease with bilateral compromised para-iliac ganglia
      is presented. A laparoscopic ovarian transposition toward a retro-uterine
      location out of the reach of the main radiation beam was made. The proximal pole
      of both ovaries was fixed to the ipsilateral uterosacral ligament. Two metallic
      clips were used to mark each distal ovarian pole to verify final position with x
      rays. Preservation of the ovarian function was documented by hormonal levels 3
      months after completing radiotherapy and regular yearly follow-up, until now.
      Normal menstruation patterns, similar to pretreatment history were recorded.

PMID- 18716551
TI  - Successful palliation of malignant ascites from peritoneal mesothelioma by
      laparoscopic intraperitoneal hyperthermic chemotherapy.
AB  - A variety of options have been proposed to treat malignant ascites but most of
      them have failed to reach a significant impact in terms of palliation.
      Laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC) could represent a
      good therapeutic tool for patients in whom medical therapies have failed and
      peritoneovenous shunting is contraindicated. Here we present a case of a 49-year
      old woman with malignant ascites secondary to peritoneal spreading of a right
      pleural mesothelioma. After failure of medical therapy, the patient underwent
      LHIPEC with Cisplatin 25 mg/m/L and Doxorubicin 7 mg/m/L. A dramatic reduction of
      ascites was documented in the postoperative period and the patient experienced
      complete abdominal symptom relief. Ascites did not recur during a follow-up
      period of 6 months. LHIPEC could be a good therapeutic option to palliate
      malignant ascites from mesothelioma in cases not eligible for a radical
      treatment. Further studies are needed to standardize dosage and perfusion
      parameters.

PMID- 18716552
TI  - Transection of the renal pelvis by endocatch bag during laparoscopic donor
      nephrectomy.
AB  - A case of inadvertent transection of the renal pelvis by the Endocatch bag during
      laparoscopic donor nephrectomy is reported. This is the second reported injury
      resulting from the Endocatch bag. We have successfully managed the injury with
      continuing good renal function after 3 years. The aim of this report is to
      increase the awareness of this potential complication and how it can be
      prevented.

PMID- 18716553
TI  - Prognostic value of tumor microinvasion and metalloproteinases expression in
      intracranial pediatric ependymomas.
AB  - Ependymomas are common pediatric intracranial neoplasms that often appear well
      circumscribed on imaging but may recur when they are treated by surgical
      resection alone. The current World Health Organization histological grading
      system does not accurately predict clinical behavior. The aim of this study was
      to identify histological and immunohistochemical features that correlate with
      clinical course in patients with ependymomas treated by gross total resection. We
      analyzed 41 pediatric ependymomas for microinvasion and correlated immunostaining
      for the metalloproteinase (MMP)-2 and MMP14 and for ezrin and bcl-2 with clinical
      outcome. Gross total resection had a significantly positive effect on overall
      survival and progression-free survival. In 28 patients who underwent gross total
      resection, microinvasion correlated with poor overall survival (p = 0.003) and
      progression-free survival (p = 0.03). Gross totally resected tumors with high
      expression of MMP2 and MMP14 had significantly shorter overall survival. Ezrin
      staining identified tumor cells invading the adjacent white matter that were not
      identified by routine stains, but Ezrin staining and bcl-2 staining did not
      provide strong prognostic correlations. The data indicate that tumor
      microinvasion into adjacent brain and tumor expression of MMP2 and MMP14 predict
      both overall and progression-free survival in pediatric ependymomas, and these
      are useful prognostic markers that may help stratify patients for adjuvant
      therapies.

PMID- 18716554
TI  - Patterns of brain infiltration and secondary structure formation in
      supratentorial ependymal tumors.
AB  - Ependymomas are generally considered to be noninfiltrative tumors that have
      discrete borders with adjacent brain tissue. Most occur in the posterior fossa or
      spinal cord. Supratentorial ependymal tumors arise near the ventricular system
      or, more rarely, within the cerebral white matter or cortex. Presented here are 6
      supratentorial ependymal tumors, 3 that primarily involve the cerebral cortex and
      3 that extend into the cortex from the underlying white matter. By microscopy,
      all of these tumors locally infiltrate the cortex and/or white matter along small
      blood vessels and axonal fiber tracts. They also form other glioma secondary
      structures including perineuronal tumor cell satellitosis and subpial tumor cell
      mounds. The 3 cortical ependymal tumors show a spectrum of features ranging from
      conventional and clear-cell ependymoma-like patterns to more angiocentric glioma
      like histology. Because ependymal tumors generally have a significantly better
      prognosis than other infiltrating gliomas, recognition of their capacity to
      infiltrate adjacent cortex and white matter is important to prevent the
      misdiagnosis of oligodendroglioma, astrocytoma, or infiltrating glioma, not
      otherwise specified. Cortical ependymomas and angiocentric gliomas may comprise a
      group of locally infiltrative ependymal tumors that are associated with an
      excellent prognosis after gross total surgical resection.

PMID- 18716555
TI  - Elevated matrix metalloproteinase-9 and degradation of perineuronal nets in
      cerebrocortical multiple sclerosis plaques.
AB  - Matrix metalloproteinases (MMPs) degrade extracellular matrix; MMP activity,
      particularly of MMP-9, is elevated in the white matter in multiple sclerosis (MS)
      patients. The cerebral cortical extracellular matrix includes perineuronal nets
      (PNs) that surround parvalbumin-positive neurons (PV-positive neurons) and are
      important for their function. We measured active and total MMP-9 levels in
      postmortem homogenates of demyelinated and nondemyelinated cerebral cortical
      regions from 9MS and 7 control cases and assessed Wisteria floribunda agglutin
      (WFA)-positive PNs in paraffin sections from 15 MS and 6 controls and PV-positive
      neurons in sections from 26 MS and 6 controls. Active MMP-9 levels were higher in
      demyelinated than in nondemyelinated or control cortex (p < 0.05). The area
      fraction positive for WFA was lower in demyelinated than nondemyelinated MS or
      control cortex; the latter difference was significant (p < 0.05). Most PV
      positive neurons in demyelinated but not intact cortex lackeda PN, and some
      showed perikaryal phosphorylated neurofilament protein accumulation. Loss of WFA
      labeled PNs was not associated with reduced PV-positive neurons numbers. Thus,
      elevated MMP-9 in cortical plaques is associated with loss of PNs; PV-positive
      neurons are preserved but show abnormal neurofilament accumulations. Matrix
      metalloproteinase-mediated degradation of PNs in cortical plaques may, therefore,
      contribute to neuronal dysfunction and degeneration in MS patients.

PMID- 18716556
TI  - Frequent gains at chromosome 7q34 involving BRAF in pilocytic astrocytoma.
AB  - Relatively little is known about the molecular changes that promote the formation
      or growth of pilocytic astrocytomas. We investigated genomic alterations in 25
      pilocytic astrocytomas, including 5 supratentorial and 20 posterior fossa tumors,
      using oligonucleotide array comparative genomic hybridization. Large changes were
      identified in 7 tumors and included gains of chromosomes 5, 6, and 7 and losses
      of chromosomes 16, 17, 19, and 22. The most common alteration was a 1.9-MB region
      of low-level gain at chromosome 7q34 identified in 17 of 20 posterior fossa
      tumors. In most tumors, the region of gain ended within the BRAF locus and
      encompassed only exons that encode the BRAF kinase domain. We confirmed copy
      number increase at the 7q34 locus using quantitative polymerase chain reaction
      with primers adjacent to the HIPK2, RAB19B, and BRAF genes. Western blot analysis
      revealed that 3 of 6 pilocytic astrocytomas with 7q34 gain contained high levels
      of phosphorylated extracellular signal-related kinase (ERK) and nitrogen
      activated protein kinase/ERK kinase (MEK), while 1 tumor lacking 7q34 gain and 2
      normal brain specimens did not. Immunohistochemical stains of a tissue microarray
      containing 43 pilocytic astrocytoma identified ERK phosphorylation in 35 (81%).
      These data indicate that focal gains at chromosome 7q34 and increased BRAF-MEK
      ERK signaling are common findings in sporadic pilocytic astrocytomas.

PMID- 18716557
TI  - Disease severity and thin filament regulation in M9R TPM3 nemaline myopathy.
AB  - The mechanism of muscle weakness was investigated in an Australian family with an
      M9R mutation in TPM3 (alpha-tropomyosin(slow)). Detailed protein analyses of 5
      muscle samples from 2 patients showed that nemaline bodies are restricted to
      atrophied Type 1 (slow) fibers in which the TPM3 gene is expressed. Developmental
      expression studies showed that alpha-tropomyosin(slow) is not expressed at
      significant levels until after birth, thereby likely explaining the childhood
      (rather than congenital) disease onset in TPM3 nemaline myopathy. Isoelectric
      focusing demonstrated that alpha-tropomyosin(slow) dimers, composed of equal
      ratios of wild-type and M9R-alpha-tropomyosin(slow), are the dominant tropomyosin
      species in 3 separate muscle groups from an affected patient. These findings
      suggest that myopathy-related slow fiber predominance likely contributes to the
      severity of weakness in TPM3 nemaline myopathy because of increased proportions
      of fibers that express the mutant protein. Using recombinant proteins and far
      Western blot, we demonstrated a higher affinity of tropomodulin for alpha
      tropomyosin(slow) compared with beta-tropomyosin; the M9R substitution within
      alpha-tropomyosin(slow) greatly reduced this interaction. Finally, transfection
      of the M9R mutated and wild-type alpha-tropomyosin(slow) into myoblasts revealed
      reduced incorporation into stress fibers and disruption of the filamentous actin
      network by the mutant protein. Collectively, these results provide insights into
      the clinical features and pathogenesis of M9R-TPM3 nemaline myopathy.

PMID- 18716558
TI  - Clonally expanded mitochondrial DNA mutations in epileptic individuals with
      mutated DNA polymerase gamma.
AB  - The instability of the mitochondrial genome in individuals harboring pathogenic
      mutations in the catalytic subunit of mitochondrial DNA (mtDNA) polymerase gamma
      (POLG) is well recognized, but the underlying molecular mechanisms remain to be
      elucidated. In 5 pediatric patients with severe myoclonic epilepsy and valproic
      acid-induced liver failure, we identified 1 novel and 4 previously described
      pathogenic mutations in the linker region of this enzyme. Although muscle
      biopsies in these patients showed unremarkable histologic features, postmortem
      liver tissue available from 1 individual exhibited large cytochrome c oxidase
      negative areas. These cytochrome c oxidase-negative areas contained 4-fold less
      mtDNA than cytochrome c oxidase-positive areas. Decreased copy numbers of mtDNA
      were observed not only in the liver, skeletal muscle, and brain but also in blood
      samples from all patients. There were also patient-specific patterns of multiple
      mtDNA deletions in different tissues, and in 2 patients, there were clonally
      expanded mtDNA point mutations. The low amount of deleted mtDNA molecules makes
      it unlikely that the deletions contribute significantly to the general
      biochemical defect. The clonal expansion of a few individual-specific deletions
      and point mutations indicates an accelerated segregation of early mtDNA mutations
      that likely are a consequence of low mtDNA copy numbers. Moreover, these results
      suggest a potential diagnostic approach for identifying mtDNA depletion in
      patients.

PMID- 18716559
TI  - Cerebral small vessel disease-induced apolipoprotein E leakage is associated with
      Alzheimer disease and the accumulation of amyloid beta-protein in perivascular
      astrocytes.
AB  - Apolipoprotein E (apoE) plays a role in the pathogenesis of Alzheimer disease
      (AD). It is involved in the receptor-mediated cellular clearance of the amyloid
      beta-protein (Abeta) and in the perivascular drainage of the extracellular fluid.
      Microvascular changes are also associated with AD and have been discussed as a
      possible reason for altered perivascular drainage. To further clarify the role of
      apoE in the perivascular and vascular pathology in AD patients, we studied its
      occurrence and distribution in the perivascular space, the perivascular neuropil,
      and in the vessel wall of AD and control cases with and without small vessel
      disease (SVD). Apolipoprotein E was found in the perivascular space and in the
      neuropil around arteries of the basal ganglia from control and AD cases
      disclosing no major differences. Western blot analysis of basal ganglia tissue
      also revealed no significant differences pertaining to the amount of full-length
      and C-terminal truncated apoE in AD cases compared with controls. In contrast,
      Abeta occurred in apoE-positive perivascular astrocytes in AD cases but not in
      controls. In blood vessels, apoE and immunoglobulin G were detected within the
      SVD-altered vessel wall. The severity of SVD was associated with the occurrence
      of apoE in the vessel wall and with that of Abeta in perivascular astrocytes.
      These results point to an important role of apoE in the perivascular clearance of
      Abeta in the human brain. The occurrence of apoE and immunoglobulin G in SVD
      lesions and in the perivascular space suggests that the presence of SVD results
      in plasma-protein leakage into the brain. It is therefore tempting to speculate
      that apoE represents a pathogenetic link between SVD and AD.

PMID- 18716560
TI  - First report of Creutzfeldt-Jakob disease occurring in 2 siblings unexplained by
      PRNP mutation.
AB  - Sibling concurrence of pathologically confirmed prion disease has only been
      reported in association with pathogenic mutation of the prion protein gene
      (PRNP). Here, we report 2 siblings with classic neuropathologic features of
      sporadic Creutzfeldt-Jakob disease unexplained by PRNP mutation or known risk
      factors for iatrogenic transmission of prion infection. Possible explanations
      include coincidental occurrence, common exposure to an unidentified environmental
      source of prions, horizontal transmission of disease, or the presence of unknown
      shared genetic predisposition.

PMID- 18716563
TI  - Epitympanic osteoma.

PMID- 18716564
TI  - Stapedotomy using continuous wave diode laser (808 nm).

PMID- 18716561
TI  - Current developments in the genetics of autism: from phenome to genome.
AB  - Despite compelling evidence from twin and family studies indicating a strong
      genetic involvement in the etiology of autism, the unequivocal detection of
      autism susceptibility genes remains an elusive goal. The purpose of this review
      is to evaluate the current state of autism genetics research, with attention
      focused on new techniques and analytic approaches. We first present a brief
      overview of evidence for the genetic basis of autism, followed by an appraisal of
      linkage and candidate gene study findings and consideration of new analytic
      approaches to the study of complex psychiatric conditions, namely, genome-wide
      association studies, assessment of structural variation within the genome, and
      the incorporation of endophenotypes in genetic analysis.

PMID- 18716565
TI  - Imaging of vestibular schwannoma with prevalent cystic component: cystic
      vestibular schwannoma.

PMID- 18716566
TI  - Petrous carotid canal dehiscence: an anatomic and radiographic study.
AB  - HYPOTHESIS: Development of the osseous petrous carotid canal is frequently
      incomplete. BACKGROUND: Although dehiscence of the carotid canal has been
      observed in previous studies, the frequency and extent of bony dehiscence have
      not been quantified. Inadvertent internal carotid artery injury occurs in 3 to 5%
      of skull base procedures, with an additional 1.9% of patients having carotid
      artery vasospasm. Documentation of the incidence of petrous apex carotid canal
      dehiscence is therefore warranted. METHODS: Ninety-nine cadaveric skulls were
      evaluated physically and by computed tomographic scan. RESULTS: Incidence of
      dorsal (endocranial) dehiscence of the petrous carotid canal was identified in
      82.83% of the left side and 88.89% of the right side. Average dimensions for left
      dorsal dehiscence measured 10.81 mm longitudinally by 4.10 mm transversely.
      Dimensions for the right averaged 11.59 mm longitudinally by 4.29 mm
      transversely. Incidence of ventral (exocranial) dehiscence was less frequent:
      37.37% on the left and 34.34% on the right. Ventral dehiscence was classified
      into major (absence of bone) and minor (fissure) types. Major dehiscence was
      observed in 8.08% and 6.06% of specimens for left and right sides, respectively;
      minor ventral dehiscence was present in 29.29% and 28.28% for left and right
      sides, respectively. CONCLUSION: Dorsal petrous carotid canal dehiscence is more
      common than previously recognized. Dehiscence of the dorsal carotid canal is a
      frequent finding with significant implications in advanced skull base approaches
      to the petrous apex, clivus, and lateral sellar compartment. Ventral dehiscence
      is a frequent finding that will become increasingly relevant as the scope of
      endoscopic skull base procedures.

PMID- 18716567
TI  - Cisplatin-induced ototoxicity: effect of intratympanic dexamethasone injections.
AB  - HYPOTHESIS: Intratympanic (IT) application of dexamethasone will reduce
      ototoxicity associated with systemic cisplatin therapy. BACKGROUND: Cisplatin is
      a common chemotherapeutic drug often dose-limited by ototoxicity attributed to
      the formation of reactive oxygen and nitrogen species damaging critical inner ear
      structures. Steroids have been shown to reduce formation of reactive oxygen
      species and thus may reduce ototoxicity. In the present pilot study, we test this
      hypothesis by IT administration of dexamethasone in a novel murine model of
      cisplatin ototoxicity. METHODS: Click- and pure-tone-evoked auditory brainstem
      responses (ABRs) in young CBA/J mice were measured. The first phase consisted of
      a dosing study to identify the optimal cisplatin dose for ototoxicity. In the
      next phase, ABR thresholds were measured in cisplatin-treated mice after 5 days
      of IT injection of 24 mg/ml of dexamethasone in 1 ear and normal saline in the
      opposite ear to serve as controls. RESULTS: Intraperitoneal injection of 14 mg/kg
      of cisplatin induces significant hearing loss (click-evoked ABR threshold
      elevation = 12 +/- 7 dB, mu +/- standard error of the mean) with acceptable
      mortality (20%). The ears that received IT dexamethasone in cisplatin-treated
      mice had minimal ABR threshold shifts with the click, 8 and 16 kHz of stimuli.
      There was no significant difference between IT dexamethasone and IT saline ears
      at 32 kHz. CONCLUSION: IT dexamethasone protected the mouse ear against cisplatin
      induced ototoxicity in a frequency-dependent manner. The present results suggest
      that IT dexamethasone may be a safe, simple, and effective intervention that
      minimizes cisplatin ototoxicity without interfering with the chemotherapeutic
      actions of cisplatin.

PMID- 18716568
TI  - Screening asymptomatic adolescent men for Chlamydia trachomatis in school-based
      health centers using urine-based nucleic acid amplification tests.
AB  - BACKGROUND: Urine-based screening for Chlamydia trachomatis using highly
      sensitive and specific nucleic acid amplification tests offers a unique
      opportunity to screen men attending school-based health centers. METHODS: As part
      of a large multicenter chlamydia screening project in men, 1434 students were
      enrolled; 1090 in high schools in Baltimore and 344 middle and high-school
      students in Denver. Students were screened for chlamydia using urine-based
      nucleic acid amplification tests at well adolescent visits, acute care visits, or
      visits for other reasons, such as sports physicals. A self-administered survey to
      ascertain sexual risk behaviors was used. Data were analyzed separately for
      Baltimore and Denver, with univariate and multivariate logistic regression
      analysis. RESULTS: The overall prevalence in asymptomatic adolescent men was 6.8%
      (7.5% in Baltimore and 4.7% in Denver, P = n.s.). Students in Denver were older,
      more racially diverse, and more likely to have had intercourse in the previous 2
      months than students in Baltimore. Students in Baltimore were more likely than
      those in Denver to have used a condom at last intercourse with casual and main
      partners. Among men in Denver but not Baltimore, condom use at last intercourse
      with both casual (OR 0.15, 95% CI, 0.03, 0.78) and main partners (OR 0.30, 95%
      CI, 0.10, 0.91) was protective against infection. The only risk factor for CT
      infection in Baltimore students was age (OR 1.47, 95% CI, 1.23, 1.75). In
      multivariate analysis that included age (as a continuous variable), race, history
      of an STI, any sex partner in the last 2 months, >1 sex partner in the past 12
      months, a new partner in the last 2 months, and condom use with last main and
      last casual partner, age (adjusted odds ratio 1.34, 95% CI, 1.11, 1.62) and black
      race (adjusted odds ratio 2.37, 95% CI, 1.21, 4.63) were the only variables
      associated with testing chlamydia positive. CONCLUSIONS: School-based health
      centers are important venues in which to perform urine-based screening for
      chlamydia in sexually active, asymptomatic males, especially in high prevalence
      communities, and such screening provides the opportunity to identify and treat
      substantial numbers of chlamydia infections.

PMID- 18716569
TI  - HIV and sexual behavior among young people: the South African paradox.

PMID- 18716580
TI  - Update: measles--United States, January-July 2008.
AB  - Sporadic importations of measles into the United States have occurred since the
      disease was declared eliminated from the United States in 2000. During January
      July 2008, 131 measles cases were reported to CDC, compared with an average of 63
      cases per year during 2000-2007. This report updates an earlier report on measles
      in the United States during 2008 and summarizes two recent U.S outbreaks among
      unvaccinated school-aged children. Among those measles cases reported during the
      first 7 months of 2008, 76% were in persons aged <20 years, and 91% were in
      persons who were unvaccinated or of unknown vaccination status. Of the 131 cases,
      89% were imported from or associated with importations from other countries,
      particularly countries in Europe, where several outbreaks are ongoing. The
      findings demonstrate that measles outbreaks can occur in communities with a high
      number of unvaccinated persons and that maintaining high overall measles, mumps,
      and rubella (MMR) vaccination coverage rates in the United States is needed to
      continue to limit the spread of measles.

PMID- 18716581
TI  - Nonfatal, unintentional, non--fire-related carbon monoxide exposures--United
      States, 2004-2006.
AB  - Carbon monoxide (CO) is a colorless, odorless, nonirritating gas that is produced
      through the incomplete combustion of hydrocarbons. Sources of CO include
      combustion devices (e.g., boilers and furnaces), motor-vehicle exhaust,
      generators and other gasoline or diesel-powered engines, gas space heaters,
      woodstoves, gas stoves, fireplaces, tobacco smoke, and various occupational
      sources. CO poisoning is a leading cause of unintentional poisoning deaths in the
      United States; it was responsible for approximately 450 deaths each year during
      1999-2004 and an estimated 15,200 emergency department (ED) visits each year
      during 2001-2003. Health effects of CO exposure can range from viral-like
      symptoms (e.g., fatigue, dizziness, headache, confusion, and nausea) to more
      severe conditions (e.g., disorientation, unconsciousness, long-term neurologic
      disabilities, coma, cardiorespiratory failure, and death). CO poisoning often is
      misdiagnosed and underdetected because of the nonspecific nature of symptoms. To
      update a previously published report and provide national estimates of CO-related
      ED visits during 2004-2006, CDC analyzed data from the National Electronic Injury
      Surveillance System--All Injury Program (NEISS-AIP) database. During 2004-2006,
      an estimated average of 20,636 ED visits for nonfatal, unintentional, non-fire
      related CO exposures occurred each year. Approximately 73% of these exposures
      occurred in homes, and 41% occurred during winter months (December-February).
      Prevention efforts targeting residential and seasonal CO exposures can
      substantially reduce CO-related morbidity.

PMID- 18716582
TI  - West Nile virus update--United States, January 1-August 19, 2008.
AB  - This report summarizes 2008 West Nile virus (WNV) surveillance data reported to
      CDC through ArboNET as of 3 a.m. Mountain Daylight Time, August 19, 2008. A total
      of 28 states have reported 236 cases of human WNV illness to CDC. A total of 137
      (58%) cases for which such data were available occurred in males; median age of
      patients was 48 years (range: 10 months-86 years). Dates of illness onset ranged
      from January 17 to August 14; two cases were fatal.

PMID- 18716583
TI  - Evaluation of an electron Monte Carlo dose calculation algorithm for electron
      beam.
AB  - The electron Monte Carlo (eMC) dose calculation algorithm of the Eclipse
      treatment planning system is based heavily upon Monte Carlo simulation of the
      linac head and modeling of the linac beam characteristics with minimal
      measurement of beam data. Commissioning of the eMC algorithm on multiple
      identical linacs provided a unique opportunity to systematically evaluate the
      algorithm with actual measurements of clinically relevant beam and dose
      parameters. In this study, measured and eMC calculated dose distributions were
      compared both along and perpendicular to electron beam direction for electron
      energy/applicator/depth combination using measurement data from four Varian 21EX
      CLINAC linear accelerator (Varian Medical System, Palo Alto, CA). Cutout factors
      for sizes down to 3 x 3 cm were also compared. Comparisons between the
      measurement and the eMC calculated values show that the R90, R80, R50, and R10
      values mostly agree within 3 mm. Measure and Calculated bremsstrahlung dose Dx
      correlates well statistically although eMC calculated Dx values are consistently
      smaller than the measured, with maximum discrepancy of 1% for the 20 MeV electron
      beams. Surface dose agrees mostly within 2%. Field width and penumbra agree
      mostly within 3mm. Calculation grid size is found to have a significant effect on
      the dose calculation. A grid size of 5 mm can produce erroneous dose
      distributions. Using a grid size of 2.5 mm and a 3% accuracy specified for the
      eMC to stop calculation iteration, the absolute output agrees with measurements
      within 3% for field sizes of 5 x 5 cm or larger. For cutout of 3 x 3 cm, however,
      the output disagreement can reach 8%. Our result indicate that eMC algorithm in
      Eclipse provides acceptable agreement with measurement data for most clinical
      situations. Calculation grid size of 2.5 mm or smaller is recommended.

PMID- 18716584
TI  - Establishing action levels for EPID-based QA for IMRT.
AB  - Although portal dosimetry is used to provide quality assurance (QA) for intensity
      modulated radiation therapy (IMRT) treatment plans, trends in agreement between
      the portal dose prediction (PDP) and the measured dose have not been clarified.
      In this work, we evaluated three scalar parameters of agreement for 152 treatment
      plans (1152 treatment fields): maximum gamma (gamma max), average gamma (gamma
      avg), and percentage of the field area with a gamma value greater than 1.0 (gamma
      % > 1). These data were then used to set clinical action levels based on the
      institutional mean and standard deviations. We found that agreement between
      measured dose and PDP was improved by recalculating the fields at lower dose
      rates. We conclude that action levels are a useful tool for standardizing the
      evaluation of EPID-based IMRT QA.

PMID- 18716585
TI  - Time-course of effects of external beam radiation on [18F]FDG uptake in healthy
      tissue and bone marrow.
AB  - The utility of PET for monitoring responses to radiation therapy have been
      complicated by metabolically active processes in surrounding normal tissues. We
      examined the time-course of [18F]FDG uptake in normal tissues using small animal
      dedicated PET during the 2 month period following external beam radiation. Four
      mice received 12 Gy of external beam radiation, in a single fraction to the left
      half of the body. Small animal [18F]FDG-PET scans were acquired for each mouse at
      0 (pre-radiation), 1, 2, 3, 4, 5, 8, 12, 19, 24, and 38 days following
      irradiation. [18F]FDG activity in various tissues was compared between irradiated
      and non-irradiated body halves before, and at each time point after irradiation.
      Radiation had a significant impact on [18F]FDG uptake in previously healthy
      tissues, and time-course of effects differed in different types of tissues. For
      example, liver tissue demonstrated increased uptake, particularly over days 3-12,
      with the mean left to right uptake ratio increasing 52% over mean baseline values
      (p < 0.0001). In contrast, femoral bone marrow uptake demonstrated decreased
      uptake, particularly over days 2-8, with the mean left to right uptake ratio
      decreasing 26% below mean baseline values (p = 0.0005). Significant effects were
      also seen in lung and brain tissue. Radiation had diverse effects on [18F]FDG
      uptake in previously healthy tissues. These kinds of data may help lay groundwork
      for a systematically acquired database of the time-course of effects of radiation
      on healthy tissues, useful for animal models of cancer therapy imminently, as
      well as interspecies extrapolations pertinent to clinical application eventually.

PMID- 18716586
TI  - Clinical experience of the importance of daily portal imaging for head and neck
      IMRT treatments.
AB  - The purpose of this study was to evaluate patient setup in head and neck IMRT
      using daily portal imaging. At our institution, orthogonal digital portal images
      are taken daily to check patient positioning prior to head and neck IMRT
      treatment. Isocenter misalignments are corrected using a couch shift (3mm action
      level). Therapists also compare the DRRs and portal images looking at points more
      distant from the isocenter, particular in the supraclavicular region, and re
      position the patient's shoulders in the mask if considered necessary. The daily
      isocenter shifts (C2 region) and frequency of patient repositioning were
      investigated by review of record-and-verify records for 15 patients. The
      magnitude of the shoulder repositioning was evaluated for 10 of these patients by
      comparing portal images and plan DRRs for a point 8 cm inferior of isocenter (T2
      T4). For all patients, pretreatment isocenter discrepancies 3mm or smaller were
      recorded for a median of 92.5% of fractions (range: 71.4 -100%). Patients were
      repositioned in the immobilization mask before treatment for a median of 14% of
      fractions (3-34%). Thirty percent of these were for shoulder shifts of 1cm or
      larger. Twenty percent of patients needed shoulder shifts of 1cm or more for more
      than 7/35 fractions, meaning that without setup based on daily imaging, parts of
      the CTV would have received less than 95% of the prescribed dose. In conclusion,
      with our current immobilization, isocenter positioning accuracy is excellent,
      while correct shoulder position is more variable, particularly for a small subset
      of patients. Frequent imaging of head and neck IMRT patients is essential to
      accurate delivery of therapy, with shoulder position an important factor.

PMID- 18716587
TI  - Radiation safety issues with positron-emission/computed tomography simulation for
      stereotactic body radiation therapy.
AB  - Stereotactic body radiation therapy (SBRT) simulations using a Stereotactic Body
      Frame (SBF: Elekta, Stockholm, Sweden) were expanded to include 18F
      deoxyglucosone positron-emission tomography (FDG PET) for treatment planning.
      Because of the length of time that staff members are in close proximity to the
      patient, concerns arose over the radiation safety issues associated with these
      simulations. The present study examines the radiation exposures of the staff
      performing SBRT simulations, and provides some guidance on limiting staff
      exposure during these simulations. Fifteen patients were simulated with PET/CT
      using the SBF. Patients were immobilized in the SBF before the FDG was
      administered. The patients were removed from the frame, injected with FDG, and
      allowed to uptake for approximately 45 minutes. After uptake, the patients were
      repositioned in the SBF. During the repositioning, exposure rates were recorded
      at the patient's surface, at the SBF surface, and at 15 cm, 30 cm, and 1 m from
      the SBF. Administered dose and the approximate time spent on patient
      repositioning were also recorded. The estimated dose to staff was compared with
      the dose to staff performing conventional diagnostic PET studies. The average
      length of time spent in close proximity (<50 cm) to the patient after injection
      was 11.7 minutes, or more than twice the length of time reported for diagnostic
      PET staff. That time yielded an estimated average dose to the staff of 26.5
      microSv per simulation. The annual occupational exposure limit is 50 mSv. Based
      on dose per simulation, staff would have to perform nearly 1900 SBRT simulations
      annually to exceed the occupational limit. Therefore, at the current rate of 50
      100 simulations annually, the addition of PET studies to SBRT simulations is safe
      for our staff. However, ALARA ("as low as reasonably achievable") principles
      still require some radiation safety considerations during SBRT simulations. The
      PET/CT-based SBRT simulations are safe and important for treatment planning that
      optimizes biologic dose distribution with highly accurate and reproducible target
      definition.

PMID- 18716588
TI  - Scatter correction for heart SPECT images using TEW method.
AB  - Radionuclide imaging has the potential to be used in quantitative analysis of the
      regional function of organs. However, quantification of SPECT images is degraded
      by many factors such as Compton photon scattering. This could have a destructive
      effect on clinical reports so it is important to do scatter correction to get
      better quality SPECT images. We intended to determine how scatter correction with
      the TEW method can help physicians who look at heart SPECT images, get better
      reports. This study used the TEW method for scatter correction, which was
      proposed by Ogawa et al.,(9) using the two narrow windows on either side of the
      photopeak (20% down and 20% up of the photopeak respectively). Injection of
      radiopharmaceutical 99mTc was used for medical imaging. In the Shariati Hospital,
      Tehran, we studied a total of 80 patients with heart disease indications (43 men
      and 37 women) over the ages of 30-80 years. Contrast and sharpness were
      considerably improved after scatter correction so physicians could look at
      defects better. In a few cases scatter correction changed heart defect reports to
      normal. Using TEW, sensitivity and specificity increased from 86% to 94% and from
      61% to 84% respectively. This method was simple to use in clinics.

PMID- 18716589
TI  - Comparison of breath-hold and free-breathing positions of an external fiducial by
      analysis of respiratory traces.
AB  - An internal target volume (ITV) accounting for respiratory-induced tumor motion
      is best obtained using 4DCT. However, when 4DCT is not available,
      inspiratory/expiratory breath-hold (BH insp, BH exp) CT images have been
      suggested as an alternative. In such cases, an external fiducial on the abdomen
      can be used as a substitute for tumor motion and CT images are acquired when the
      marker position matches - as judged by the therapist/physicist - its positions at
      previously determined free-breathing (FB) respiratory extrema (FB insp, FB exp).
      In this study we retrospectively determined the accuracy of these matches. Free
      breathing 4DCT images were acquired, followed by BH insp and BH exp CT images for
      25 patients with non-small-cell lung cancer. Respiration was monitored using a
      commercial external fiducial system, which generates positional information while
      CT studies are conducted. Software was written for statistically analyzing the
      displacement of the external fiducial during BH insp and BH exp CT acquisition
      and comparing these displacements with corresponding mean FB extrema positions
      (FB insp and FB exp, respectively) using a Student's t-test. In 72% of patients,
      mean positions at BH insp differed significantly from mean positions at FB insp
      (p < 0.05: 0.13 - 1.40 cm). In 92% of patients, mean positions at BH exp differed
      significantly from mean positions at FB exp (p < 0.05: 0.03 - 0.70 cm), although
      this difference was smaller than 0.5 cm in many cases (median = 0.34 cm). Our
      findings indicate that relying solely on abdominal external markers for accurate
      BH CT imaging in order to accurately estimate FB extrema positions may be subject
      to significant error.

PMID- 18716590
TI  - Comparison of the KonRad IMRT and XiO treatment planning systems.
AB  - Reducing the treatment time for IMRT patients is highly desirable. The objective
      of this work was to evaluate the new clinical Siemens KonRad inverse treatment
      planning system (TPS) and compare it to the CMS XiO TPS with special emphasis on
      the segmentation efficiency. For head and neck, liver and prostate cancer
      patients, step-and-shoot IMRT plans were designed using both CMS XiO and Siemens
      KonRad TPS. Number, direction and energy of beams used were the same in the plans
      from both systems for each treatment site. The plans were optimized to achieve
      the same clinical objectives concerning dose to the target volume and to the
      relevant organs-at-risk (OARs). The number of intensity levels were minimized
      until the clinical objectives could not be achieved anymore. Dose-volume
      histograms (DVHs), mean- and maximum-doses were compared, as well as the number
      of beam segments and monitor units (MUs). The beams of each plan were delivered
      individually on a MapCheck device to verify the agreement between calculations
      and measurements to be less than 3%-3 mm distance-to-agreement. Plans optimized
      with KonRad resulted in fewer segments and lower number of MUs and therefore
      reduced delivery time on average by 20%, while achieving similar dose
      distributions. CMS XiO plans exhibited a slightly steeper dose fall-off outside
      the target volumes; however the difference was not clinically significant. DVHs
      to OARs were comparable. All calculated dose distributions passed the 3%-3 mm
      verification check.

PMID- 18716591
TI  - Evaluation of MVCT images with skin collimation for electron beam treatment
      planning.
AB  - This study assessed the potential of using megavoltage CT (MVCT) images taken
      with high density skin collimation in place for electron beam treatment planning.
      MVCT images were taken using the TomoTherapy Hi-Art system (TomoTherapy Inc.,
      Madison, WI), and the CT numbers were converted to density by calibrating the Hi
      Art system using an electron density phantom. Doses were computed using MVCT
      images and kVCT images and compared by calculating dose differences in the
      uniform dose region ( > 90%, excluding buildup region) and calculating distance
      to-agreement (DTA) in high dose-gradient regions (penumbra and distal falloff,
      90%-10%). For 9 and 16 MeV electron beams of 10 x 10 cm calculated on a
      homogeneous CIRS Plastic Water (Computerized Imaging Research Systems Inc.,
      Norfolk, VA) phantom without skin collimation, the maximum dose differences were
      2.3% and the maximum DTAs were 2.0 mm for both beams. The same phantom was then
      MVCT scanned nine times with square skin collimators of Cerrobend on its surface 
      field sizes of 3 x 3, 6 x 6, and 10 x 10 cm and thicknesses of 6, 8, and 10 mm.
      Using the Philips Pinnacle 3 treatment planning system (Philips Medical Systems,
      N.A., Bothwell, WA), a treatment plan was created for combinations of electron
      energies of 6, 9, 12, and 16 MeV and each field size. The same treatment plans
      were calculated using kVCT images of the phantom with regions-of-interest (ROI)
      manually drawn to duplicate the sizes, shapes, and density of the skin
      collimators. With few exceptions, the maximum dose differences exceeded +/-5% and
      the DTAs exceeded 2 mm. We determined that the dose differences were due to small
      distortions in the MVCT images created by the high density material and
      manifested as errors in the phantom CT numbers and in the shape of the skin
      collimator edges. These results suggest that MVCT images without skin collimation
      have potential for use in patient electron beam treatment planning. However, the
      small distortion in images with skin collimation makes them unsuitable for
      clinical use.

PMID- 18716592
TI  - A commissioning procedure for breast intracavitary electronic brachytherapy
      systems.
AB  - In this work, we report a comprehensive quality assurance (QA) process for the
      commissioning of an Electronic Brachytherapy (EB) system at one of the first U.S.
      sites to apply the device clinically. Thus far, EB systems have been released
      only for intracavitary breast treatments. As such, EB as an Accelerated Partial
      Breast Irradiation (APBI) treatment modality is relatively unstudied and is
      unfamiliar to many medical physicists. We present our documented experience as a
      guide for other institutions' EB commissioning process. Our tests included eight
      elements: A) well-chamber constancy, B) beam stability, C) source positional
      accuracy, D) output stability, E) timer linearity, F) dummy marker/source
      position coincidence, G) controller functionality and safety interlocks, and H)
      treatment planning data verification following the AAPM TG-43 recommendations.
      Together with TG-43, our methodology provides a comprehensive EB system check for
      medical physicists commissioning such a device.

PMID- 18716593
TI  - Image guided IMRT dosimetry using anatomy specific MOSFET configurations.
AB  - We have investigated the feasibility of using a set of multiple MOSFETs in
      conjunction with the mobile MOSFET wireless dosimetry system, to perform a
      comprehensive and efficient quality assurance (QA) of IMRT plans. Anatomy
      specific MOSFET configurations incorporating 5 MOSFETs have been developed for a
      specially designed IMRT dosimetry phantom. Kilovoltage cone beam computed
      tomography (kV CBCT) imaging was used to increase the positional precision and
      accuracy of the detectors and phantom, and so minimize dosimetric uncertainties
      in high dose gradient regions. The effectiveness of the MOSFET based dose
      measurements was evaluated by comparing the corresponding doses measured by an
      ion chamber. For 20 head and neck IMRT plans the agreement between the MOSFET and
      ionization chamber dose measurements was found to be within -0.26 +/- 0.88% and
      0.06 +/- 1.94% (1 sigma) for measurement points in the high dose and low dose
      respectively. A precision of 1 mm in detector positioning was achieved by using
      the X-Ray Volume Imaging (XVI) kV CBCT system available with the Elekta Synergy
      Linear Accelerator. Using the anatomy specific MOSFET configurations,
      simultaneous measurements were made at five strategically located points covering
      high dose and low dose regions. The agreement between measurements and calculated
      doses by the treatment planning system for head and neck and prostate IMRT plans
      was found to be within 0.47 +/- 2.45%. The results indicate that a cylindrical
      phantom incorporating multiple MOSFET detectors arranged in an anatomy specific
      configuration, in conjunction with image guidance, can be utilized to perform a
      comprehensive and efficient quality assurance of IMRT plans.

PMID- 18716594
TI  - In-house auto cutoff sensor device for radiotherapy machine to monitor patient
      movements.
AB  - Radiotherapy is an effective treatment method for cancers. During radiation
      treatment, a patient must be in the same position from the start to the end of
      radiation treatment. Patient movements are usually monitored by the radiation
      technologists through the closed circuit television (CCTV) during treatment. If
      the patient makes a small movement, it is difficult to be noticed by them. In the
      present work, a simple patient movement monitoring device (PMMD) is fabricated to
      monitor the patient movement. It uses an electronic sensing device. It
      continuously monitors the patient's position while the radiation treatment is in
      process. The device has been retrospectively tested on 86 patients whose movement
      and distance were measured. The results show that 24 patients moved 1 cm to 2.5
      cm from their initial position during the external beam radiotherapy (EBRT).
      Hence, the device can potentially be used to control and monitor patient movement
      during EBRT. In addition, an audible alarm situated at the control panel of the
      treatment room is provided with this device to alert the radiation technologists.
      It is an inexpensive, compact device which can be used in any radiotherapy
      machine. It can prevent patients from being treated in a wrong position and
      therefore improve the quality of the radiation treatment.

PMID- 18716595
TI  - Radiation transmission, leakage and beam penumbra measurements of a micro
      multileaf collimator using GafChromic EBT film.
AB  - Micro-multileaf collimator systems coupled to linear accelerators for
      radioneurosurgery treatments require a rigorous dosimetric characterization in
      order to be used in 3D conformal and intensity modulated stereotactic
      radiosurgery and radiotherapy applications. This characterization involves high
      precision measurements of leaf transmission, leakage and beam penumbra through
      the collimation system and requires the use of detectors with high spatial
      resolution, high sensitivity and practically no energy dependence. In this work
      the use of GafChromic EBT radiochromic film to measure the basic dosimetric
      properties of the m3-mMLC (BrainLAB, Germany) micro-multileaf collimator system
      integrated to a 6 MV linear accelerator, is reported. Results show that average
      values of transmission and leakage radiation are 0.93 +/- 0.05% and 1.08 +/-
      0.08%, respectively. The 80-20% beam penumbra were found to be 2.26 +/- 0.11 mm
      along the leaf side (perpendicular to leaf motion) and 2.31 +/- 0.11 mm along the
      leaf end (parallel to leaf motion) using square field sizes ranging from 9.1 to
      1.8 cm. These measurements are in agreement with values reported in the
      literature for the same type of mMLC using different radiation detectors.

PMID- 18716596
TI  - Unified dosimetry index (UDI): a figure of merit for ranking treatment plans.
AB  - We have formulated a unified dosimetry index (UDI) that computes, for any given
      treatment plan, its deviations in terms of dose coverage, conformity,
      homogeneity, and dose gradient vis-a-vis an ideal plan (which we define as a
      dosimetry plan of perfect dose coverage, conformity, homogeneity, and step-wise
      fall-off to zero dose outside the planning target volume). In order to validate
      the UDI scoring system, 21 stereotactic cranial radiosurgery cases were evaluated
      retrospectively. The cases were planned on the BrainSCAN treatment planning
      system (BrainLAB, Feldkirchen, Germany) using 6 to 8 non-coplanar static beams
      collimated with the micro multi-leaf collimator (mMLC). We suggest a technique
      for creating a ranking system that can be utilized for plan evaluation and
      comparison between multiple plans. Under this system treatment plans are
      classified as "excellent", "good", "average", or "poor". The proposed ranking
      system can be utilized as a general guide for generating an optimal dosimetry
      plan for external beam radiation therapy.

PMID- 18716599
TI  - Editorial: Taking advantage of the JACMP website.

PMID- 18716597
TI  - Dosimetric verification of micro-MLC based intensity modulated radiation therapy.
AB  - A methodology for the dosimetric verification of micro-multileaf collimator MMLC)
      based intensity modulated radiation therapy (IMRT) plans intended for
      stereotactic applications is described. The procedure is similar to that of
      conventional IMRT patient-specific quality assurance with some notable
      exceptions. Relative dosimetry measurements are performed with radiographic film,
      a commercial film-scanning system and a dose-image registration program. Film
      dosimetry results are within +/- 3.0% of calculated distributions or within 2.0
      mm distance to agreement. Absolute dosimetry measurements are performed with a
      small volume ion-chamber and a commercially available stereotactic phantom. The
      cumulative dose from all beams is within +/- 2.0 % of the prescribed dose. Large
      deviations may be observed from individual beams since the smaller IMRT fields
      tend to have very few high-dose and low-gradient regions. An independent program
      that examines the treatment MLC file is used to estimate the central axis dose
      from each beam and provide a dose image that can be assessed alongside the
      intended fluence distribution prior to treatment. Tolerances for relative and
      absolute dosimetry of MMLC-based IMRT treatments are tighter than what is
      typically reported for conventional MLC-based IMRT. Also, the time commitment for
      the IMRT QA is slightly longer than of conventional MLC-based IMRT due to QA
      processes which check the mechanical alignment of the MMLC device with the laser
      and radiation isocentre.

PMID- 18716600
TI  - The underutilization of hemodialysis in patients with salicylate poisoning.

PMID- 18716601
TI  - Corin: new insights into the natriuretic peptide system.
AB  - Natriuretic peptides are important in regulating salt and body-fluid balance. In
      cells, these peptides are made as precursor forms that are converted to active
      forms by proteolyic processing. Corin is a transmembrane serine protease
      identified in the heart. Corin converts pro-atrial natriuretic peptide (pro-ANP)
      to active ANP in a sequence-specific manner. In mice, lack of corin prevents the
      conversion of pro-ANP to ANP and causes salt-sensitive hypertension. The
      hypertensive phenotype is exacerbated when the mice become pregnant. In humans,
      single nucleotide polymorphisms in the corin gene have been identified in African
      Americans with hypertension and cardiac hypertrophy. These data indicate that
      corin is important in maintaining normal blood pressure in vivo and that corin
      deficiency may contribute to hypertension and heart disease in patients.

PMID- 18716602
TI  - Testing for causality and prognosis: etiological and prognostic models.
AB  - Etiological research aims to investigate the causal relationship between putative
      risk factors (or determinants) and a given disease or other outcome. In contrast,
      prognostic research aims to predict the probability of a given clinical outcome
      and in this perspective the pathophysiology of the disease is not an issue.
      Multivariate modeling is a fundamental tool both to infer causality and to
      investigate prognostic factors in epidemiological research. The analytical
      approaches to etiological and prognostic studies are strictly dependent on the
      research question and imply knowledge of the main statistical procedures for
      model building and data interpretation. In this paper we describe the application
      of multivariate statistical modeling in etiological and prognostic research. We
      will mainly focus on the differences in model building and data interpretation
      between these two areas of epidemiologic research.

PMID- 18716603
TI  - EMT and proteinuria as progression factors.
AB  - Tubulointerstitial fibrosis is an integral part of the structural changes of the
      kidney in chronic progressive renal failure. The accumulation of the
      extracellular matrix in the tubulointerstitial space is mediated mainly by
      myofibroblasts. These are derived from resident interstitial fibroblasts, tubular
      epithelial cells, periadventitial cells, and possibly also mesenchymal stem cells
      and endothelial cells. Fibrosis is usually preceded by tubulointerstitial
      infiltration of mononuclear inflammatory cells. Proteinuria is one of several
      mechanisms of primary glomerular or vascular disease to transmit the disease
      process to the interstitial space. Increased protein filtration may have direct
      toxic effects on tubular epithelial cells, induce chemokine and cytokine
      secretion and result in increased expression of adhesion molecules, all
      contributing to the influx of mononuclear cells. Inflammatory cells in return
      secrete cytokines, which stimulate resident fibroblasts and tubular epithelial
      cells to differentiate into matrix-producing cells. The phenotypic conversion of
      primary epithelial cells into mesenchymal cells, termed epithelial-mesenchymal
      transition (EMT), has been studied in great detail in recent years. Several
      signal transduction pathways of this process have been clarified and may
      eventually result in novel therapeutic approaches. The severity of proteinuria
      and the extent of EMT have both been associated with the decline in renal
      function in clinical studies. Limiting proteinuria results in a slower decline of
      renal function deterioration, whereas reducing EMT has had beneficial effects in
      a number of animal studies, including those indicating reversal of fibrotic
      lesions. However, the association between proteinuria and EMT and vice versa is
      far from clear and has not been carefully studied.

PMID- 18716604
TI  - Increased left ventricular mass in children with autosomal dominant polycystic
      kidney disease and borderline hypertension.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary
      condition that may be diagnosed in utero. Our goal was to evaluate symptoms of
      ADPKD in children, including left ventricular mass index (LVMI), renal volume,
      renal function and microalbuminuria in relation to systolic and diastolic blood
      pressure. Eighty-five children were stratified by blood pressure into three
      cohorts: hypertensive (95th percentile and over), borderline hypertensive (75
      95th percentile) and normotensive (75th percentile and below). There were no
      differences in gender, age, height, renal function, or microalbuminuria between
      the groups. Both the hypertensive and borderline hypertensive children had a
      significantly higher LVMI than normotensive children, with no significant
      difference between hypertensive and borderline hypertensive groups. There was a
      significant correlation between renal volume and both systolic and diastolic
      blood pressures in all subjects. Renal volume in hypertensive children was
      significantly larger than in the borderline hypertensive group, with no
      significant difference between normotensive and borderline hypertensive groups.
      These findings show that an increase in LVMI may be detected earlier than an
      increase in renal volume in children with ADPKD and borderline hypertension,
      suggesting that close monitoring of cardiac status is indicated in these
      children.

PMID- 18716605
TI  - Genistein protects the kidney from cisplatin-induced injury.
AB  - Oxidative stress and inflammation contribute to the pathogenesis of cisplatin
      induced nephrotoxicity. We found that genistein, a tyrosine kinase inhibitor with
      broad specificities, and which also has estrogen-like activity, had protective
      effects on cisplatin-induced renal injury in mice. Genistein significantly
      decreased reactive oxygen species production, the expression of intercellular
      adhesion molecule-1 and monocyte chemoattractant protein-1 proteins, as well as
      the translocation of the p65 subunit of nuclear factor-kappaB into the nucleus
      and the infiltration of macrophages, all of which were increased in the kidney by
      cisplatin treatment. Genistein also decreased cisplatin-induced apoptosis by
      regulating p53 induction in kidney. Genistein significantly reduced reactive
      oxygen species production in cisplatin-treated normal human kidney HK-2 cells.
      These studies show that genistein or similar compounds might be useful in
      prevention of cisplatin-induced renal injury.

PMID- 18716606
TI  - Modeling residential fine particulate matter infiltration for exposure
      assessment.
AB  - Individuals spend the majority of their time indoors; therefore, estimating
      infiltration of outdoor-generated fine particulate matter (PM(2.5)) can help
      reduce exposure misclassification in epidemiological studies. As indoor
      measurements in individual homes are not feasible in large epidemiological
      studies, we evaluated the potential of using readily available data to predict
      infiltration of ambient PM(2.5) into residences. Indoor and outdoor light
      scattering measurements were collected for 84 homes in Seattle, Washington, USA,
      and Victoria, British Columbia, Canada, to estimate residential infiltration
      efficiencies. Meteorological variables and spatial property assessment data
      (SPAD), containing detailed housing characteristics for individual residences,
      were compiled for both study areas using a geographic information system.
      Multiple linear regression was used to construct models of infiltration based on
      these data. Heating (October to February) and non-heating (March to September)
      season accounted for 36% of the yearly variation in detached residential
      infiltration. Two SPAD housing characteristic variables, low building value, and
      heating with forced air, predicted 37% of the variation found between detached
      residential infiltration during the heating season. The final model,
      incorporating temperature and the two SPAD housing characteristic variables, with
      a seasonal interaction term, explained 54% of detached residential infiltration.
      Residences with low building values had higher infiltration efficiencies than
      other residences, which could lead to greater exposure gradients between low and
      high socioeconomic status individuals than previously identified using only
      ambient PM(2.5) concentrations. This modeling approach holds promise for
      incorporating infiltration efficiencies into large epidemiology studies, thereby
      reducing exposure misclassification.

PMID- 18716607
TI  - Cholinesterase inhibition in chlorpyrifos workers: Characterization of biomarkers
      of exposure and response in relation to urinary TCPy.
AB  - The objective of this study was to evaluate the quantitative relation between
      measured red blood cell acetylcholinesterase (RBC AChE) and plasma
      butyrylcholinesterase (BuChE) activities with exposure to chlorpyrifos (CPF) as
      assessed by measurement of urinary 3,5,6-trichloro-2-pyridinol (TCPy) in a study
      group of workers occupationally exposed in the manufacture of CPF and a referent
      group of chemical manufacturing workers. Measures of plasma BuChE and RBC AChE
      activity and urinary TCPy concentration collected over a year-long study (1999
      2000) in CPF-exposed workers (n=53) and referents (n=60) were analyzed using
      linear mixed models to characterize exposure-response relationships.
      Intraindividual variability in cholinesterase measures was compared between CPF
      exposed workers and referents. Urinary TCPy concentrations in CPF workers were
      substantially elevated compared to referents, with median and 95th percentile
      concentrations during typical employment conditions 10-fold and more than 30-fold
      higher, respectively, than corresponding measures in the referents.
      Intraindividual variability in cholinesterase activities was substantial, with
      17% of unexposed referents experiencing one or more plasma BuChE measures more
      than 20% below baseline over a year of repeated, periodic measurements. RBC AChE
      activity, an early biomarker of effect, was unrelated to urinary TCPy
      concentration over the entire range of exposure, up to 1000 microg TCPy/g
      creatinine (Cr). Plasma BuChE activity, a non-adverse biomarker of exposure, was
      negatively related to urinary TCPy concentrations above approximately 110 microg
      TCPy/g Cr. No-effect levels for inhibition of plasma BuChE and RBC AChE
      corresponding to absorbed doses of CPF of approximately 5 and greater than 50
      microg/kg/day, respectively, were identified. These findings are consistent with
      previous no-effect level determinations for ChE inhibition in humans and suggest
      that general population CPF exposure levels are substantially below the
      identified no-effect levels. The dose-response relationships observed in this
      study are consistent with predictions from the previously published
      physiologically based pharmacokinetic/pharmacodynamic model for CPF.
      Intraindividual variability in measured cholinesterase activities in referents
      was substantial, suggesting that ongoing monitoring programs may have a
      substantial rate of false positives.

PMID- 18716608
TI  - Genetic modification of plant architecture and variety improvement in rice.
AB  - The structure of the aerial part of a plant, referred to as plant architecture,
      is subject to strict genetic control, and grain production in cereal crops is
      governed by an array of agronomic traits. Rice is one of the most important
      cereal crops and is also a model plant for molecular biological research.
      Recently, significant progress has been made in isolating and collecting rice
      mutants that exhibit altered plant architecture. In this article we summarize the
      recent progress in understanding the basic patterning mechanisms involved in the
      regulation of tillering (branching) pattern, stem structure and leaf arrangement
      in rice plants. We discuss the relationship between the genetic modification of
      plant architecture and the improvement of pivotal agronomic traits in rice.

PMID- 18716609
TI  - Transmitted duplication of 8p23.1-8p23.2 associated with speech delay, autism and
      learning difficulties.
AB  - Duplications of distal 8p with and without significant clinical phenotypes have
      been reported and are often associated with an unusual degree of structural
      complexity. Here, we present a duplication of 8p23.1-8p23.2 ascertained in a
      child with speech delay and a diagnosis of ICD-10 autism. The same duplication
      was found in his mother who had epilepsy and learning problems. A combination of
      cytogenetic, FISH, microsatellite, MLPA and oaCGH analysis was used to show that
      the duplication extended over a minimum of 6.8 Mb between 3 539 893 and 10 323
      426 bp. This interval contains 32 novel and 41 known genes, of which only
      microcephalin (MCPH1) is a plausible candidate gene for autism at present. The
      distal breakpoint of the duplicated region interrupts the CSMD1 gene in 8p23.2
      and the medial breakpoint lies between the MSRA and RP1L1 genes in 8p23.1.An
      interchromosomal insertion between a normal and polymorphically inverted
      chromosome 8 is proposed to explain the origin of this duplication. Further
      mapped imbalances of distal 8p are needed to determine whether the autistic
      component of the phenotype in this family results from the cumulative imbalance
      of many genes or dosage imbalance of an individual susceptibility gene.

PMID- 18716610
TI  - Genomic screening identifies novel linkages and provides further evidence for a
      role of MYH9 in nonsyndromic cleft lip and palate.
AB  - Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth
      anomaly that requires prolonged multidisciplinary rehabilitation. Although
      variation in several genes has been identified as contributing to NSCLP, most of
      the genetic susceptibility loci have yet to be defined. To identify additional
      contributory genes, a high-throughput genomic scan was performed using the
      Illumina Linkage IVb Panel platform. We genotyped 6008 SNPs in nine non-Hispanic
      white NSCLP multiplex families and a single large African-American NSCLP
      multiplex family. Fourteen chromosomal regions were identified with LOD>1.5,
      including six regions not previously reported. Analysis of the data from the
      African-American and non-Hispanic white families revealed two likely chromosomal
      regions: 8q21.3-24.12 and 22q12.2-12.3 with LOD scores of 2.98 and 2.66,
      respectively. On the basis of biological function, syndecan 2 (SDC2) and growth
      differentiation factor 6 (GDF6) in 8q21.3-24.12 and myosin heavy-chain 9, non
      muscle (MYH9) in 22q12.2-12.3 were selected as candidate genes. Association
      analyses from these genes yielded marginally significant P-values for SNPs in
      SDC2 and GDF6 (0.01<or=P<0.05). Evidence for an altered transmission was found
      for four MYH9 SNPs (P<0.01). SNP rs1002246 exhibited altered transmission by all
      analytic methods. However, analysis of two SNP MYH9 haplotypes did not identify a
      single high-risk haplotype. Our results confirm a previous report that 8q21.3
      24.12 may harbor a clefting gene and identify 22q12.2-12.3 as a new candidate
      region that contains MYH9. Most importantly, we confirm the previous report of an
      association with MYH9.

PMID- 18716611
TI  - Natural selection and the molecular basis of electrophoretic variation at the
      coagulation F13B locus.
AB  - Electrophoretic analysis of protein variation at the coagulation F13B locus has
      previously revealed three alleles, with alleles 1, 2, and 3 each being at high
      frequency in European, African, and Asian populations, respectively. To determine
      if this unusual pattern of interpopulation differentiation reflects local natural
      selection or neutral genetic drift, we re-sequenced 4.6 kb of the gene,
      encompassing all exons, splice junctions, and 1.4 kb of the promoter, in African,
      European, and Asian samples. These analyses revealed three major lineages, which
      correspond to the common protein alleles and differ from each other at a non
      synonymous substitution in exon 3 and a novel splice acceptor in intron K. There
      is previous evidence that these lineages are not functionally equivalent; we
      therefore carried out case-control analyses and confirmed that variability at
      F13B modulates susceptibility and/or survivorship in coronary artery disease
      (P<0.05) and type II diabetes within the coronary artery disease cohort (P<0.01).
      Tajima's D and Fu and Li's tests did not indicate significant departures from
      neutral expectations. However, publicly available data from SeattleSNPs and
      HapMap do indicate highly unusual levels of population differentiation (P=0.003)
      and an excess of allele-specific, extended haplotype homozygosity within the
      African population (P=0.0125). Possible causes of this putative signal of
      selection include hematophagous organisms, infection by pathogens that cause
      disseminated intravascular coagulation, and metabolic or dietary factors.

PMID- 18716612
TI  - Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients
      involving the same AluY repeat.
AB  - Lysinuric protein intolerance (LPI) is a rare autosomal inherited disease caused
      by defective cationic aminoacid transport 4F2hc/y(+)LAT-1 at the basolateral
      membrane of epithelial cells in the intestine and kidney. LPI is a multisystemic
      disease with a variety of clinical symptoms such as hepatosplenomegaly,
      osteoporosis, hypotonia, developmental delay, pulmonary insufficiency or end
      stage renal disease. The SLC7A7 gene, which encodes the y(+)LAT-1 protein, is
      mutated in LPI patients. Mutation analysis of the promoter localized in intron 1
      and all exons of the SLC7A7 gene was performed in 11 patients from 9 unrelated
      LPI families. Point mutation screening was performed by exon direct sequencing
      and a new multiplex ligation probe amplification (MLPA) assay was set up for
      large rearrangement analysis. Eleven SLC7A7-specific mutations were identified,
      seven of them were novel: p.L124P, p.C425R, p.R468X, p.Y274fsX21, c.625+1G>C,
      DelE4-E11 and DelE6-E11. The novel large deletions originated by the
      recombination of Alu repeats at introns 3 and 5, respectively, with the same AluY
      sequence localized at the SLC7A7 3' region. The novel MLPA assay is robust and
      valuable for LPI molecular diagnosis. Our results suggest that genomic
      rearrangements of SLC7A7 play a more important role in LPI than has been
      reported, increasing the detection rate from 5.1 to 21.4%. Moreover, the 3'
      region AluY repeat could be a recombination hot spot as it is involved in 38% of
      all SLC7A7 rearranged chromosomes described so far.

PMID- 18716614
TI  - Long-term outcome of presymptomatic testing in Huntington disease.
AB  - Our study on long-term outcome of presymptomatic testing for Huntington disease
      had two aims: the comparison of the psychological well-being and social
      adjustment of carriers and non-carriers of the mutation, and the identification
      of psychological determinants to improve care/support of testees. We performed a
      cross-sectional study of 351 persons who underwent presymptomatic testing. Those
      who had motor signs were excluded from the comparison of asymptomatic carrier and
      non-carriers. A structured interview including five self-report scales and the
      MINI (Mini International Neuropsychiatric Inventory) was proposed to detect a
      psychopathology or problem with social adjustment.We interviewed 119 testees
      (53%), 62 non-carriers and 57 carriers after a mean delay of 3.7 years (range:
      0.32 to 8.9) after their result. Depression was frequent in asymptomatic carriers
      (58%). Interestingly, the self reported impact of the test showed that 27% of non
      carriers did not cope well with a favourable result, and a significant percentage
      of non-carriers (24%) were depressed during follow-up. Multivariate analysis
      showed that only a previous episode of depression was predictive of depression
      after genetic testing in both carriers and non-carriers of the HD mutation
      (P<0.0001).Psychological support is necessary for all testees regardless of the
      result of their presymptomatic test, because psychiatric care is often needed by
      both carriers and non-carriers.

PMID- 18716613
TI  - The mutation spectrum in RECQL4 diseases.
AB  - Mutations in the RECQL4 gene can lead to three clinical phenotypes with
      overlapping features. All these syndromes, Rothmund-Thomson (RTS), RAPADILINO and
      Baller-Gerold (BGS), are characterized by growth retardation and radial defects,
      but RAPADILINO syndrome lacks the main dermal manifestation, poikiloderma that is
      a hallmark feature in both RTS and BGS. It has been previously shown that RTS
      patients with RECQL4 mutations are at increased risk of osteosarcoma, but the
      precise incidence of cancer in RAPADILINO and BGS has not been determined. Here,
      we report that RAPADILINO patients identified as carriers of the c.1390+2delT
      mutation (p.Ala420_Ala463del) are at increased risk to develop lymphoma or
      osteosarcoma (6 out of 15 patients). We also summarize all the published RECQL4
      mutations and their associated cancer cases and provide an update of 14 novel
      RECQL4 mutations with accompanying clinical data.

PMID- 18716615
TI  - Current regulatory and legal considerations for follow-on biologics.

PMID- 18716616
TI  - Imaging as a tumor biomarker in oncology drug trials for lung cancer: the FDA
      perspective.
AB  - The US Food and Drug Administration (FDA) is committed to working with the
      oncology community to expedite the drug evaluation process in view of the many
      promising new oncology drugs under laboratory development and the time and
      expense required for such new drugs to reach the patient population. One
      significant advance would be to enable quantitative imaging as a tumor biomarker.
      The FDA is working with the pharmaceutical industry, academia, and sister
      stakeholders in the government, primarily through collaborative educational and
      research efforts, to identify how imaging can serve this function.

PMID- 18716617
TI  - Counterintuitive carbon-to-nutrient coupling in an Arctic pelagic ecosystem.
AB  - Predicting the ocean's role in the global carbon cycle requires an understanding
      of the stoichiometric coupling between carbon and growth-limiting elements in
      biogeochemical processes. A recent addition to such knowledge is that the
      carbon/nitrogen ratio of inorganic consumption and release of dissolved organic
      matter may increase in a high-CO(2) world. This will, however, yield a negative
      feedback on atmospheric CO(2) only if the extra organic material escapes
      mineralization within the photic zone. Here we show, in the context of an Arctic
      pelagic ecosystem, how the fate and effects of added degradable organic carbon
      depend critically on the state of the microbial food web. When bacterial growth
      rate was limited by mineral nutrients, extra organic carbon accumulated in the
      system. When bacteria were limited by organic carbon, however, addition of labile
      dissolved organic carbon reduced phytoplankton biomass and activity and also the
      rate at which total organic carbon accumulated, explained as the result of
      stimulated bacterial competition for mineral nutrients. This counterintuitive
      'more organic carbon gives less organic carbon' effect was particularly
      pronounced in diatom-dominated systems where the carbon/mineral nutrient ratio in
      phytoplankton production was high. Our results highlight how descriptions of
      present and future states of the oceanic carbon cycle require detailed
      understanding of the stoichiometric coupling between carbon and growth-limiting
      mineral nutrients in both autotrophic and heterotrophic processes.

PMID- 18716618
TI  - ATP drives lamina propria T(H)17 cell differentiation.
AB  - Interleukin (IL)-17-producing CD4(+) T lymphocytes (T(H)17 cells) constitute a
      subset of T-helper cells involved in host defence and several immune disorders.
      An intriguing feature of T(H)17 cells is their selective and constitutive
      presence in the intestinal lamina propria. Here we show that adenosine 5'
      triphosphate (ATP) that can be derived from commensal bacteria activates a unique
      subset of lamina propria cells, CD70(high)CD11c(low) cells, leading to the
      differentiation of T(H)17 cells. Germ-free mice exhibit much lower concentrations
      of luminal ATP, accompanied by fewer lamina propria T(H)17 cells, compared to
      specific-pathogen-free mice. Systemic or rectal administration of ATP into these
      germ-free mice results in a marked increase in the number of lamina propria
      T(H)17 cells. A CD70(high)CD11c(low) subset of the lamina propria cells expresses
      T(H)17-prone molecules, such as IL-6, IL-23p19 and transforming-growth-factor
      beta-activating integrin-alphaV and -beta8, in response to ATP stimulation, and
      preferentially induces T(H)17 differentiation of co-cultured naive CD4(+) T
      cells. The critical role of ATP is further underscored by the observation that
      administration of ATP exacerbates a T-cell-mediated colitis model with enhanced
      T(H)17 differentiation. These observations highlight the importance of commensal
      bacteria and ATP for T(H)17 differentiation in health and disease, and offer an
      explanation of why T(H)17 cells specifically present in the intestinal lamina
      propria.

PMID- 18716619
TI  - CDK targets Sae2 to control DNA-end resection and homologous recombination.
AB  - DNA double-strand breaks (DSBs) are repaired by two principal mechanisms: non
      homologous end-joining (NHEJ) and homologous recombination (HR). HR is the most
      accurate DSB repair mechanism but is generally restricted to the S and G2 phases
      of the cell cycle, when DNA has been replicated and a sister chromatid is
      available as a repair template. By contrast, NHEJ operates throughout the cell
      cycle but assumes most importance in G1 (refs 4, 6). The choice between repair
      pathways is governed by cyclin-dependent protein kinases (CDKs), with a major
      site of control being at the level of DSB resection, an event that is necessary
      for HR but not NHEJ, and which takes place most effectively in S and G2 (refs 2,
      5). Here we establish that cell-cycle control of DSB resection in Saccharomyces
      cerevisiae results from the phosphorylation by CDK of an evolutionarily conserved
      motif in the Sae2 protein. We show that mutating Ser 267 of Sae2 to a non
      phosphorylatable residue causes phenotypes comparable to those of a sae2Delta
      null mutant, including hypersensitivity to camptothecin, defective sporulation,
      reduced hairpin-induced recombination, severely impaired DNA-end processing and
      faulty assembly and disassembly of HR factors. Furthermore, a Sae2 mutation that
      mimics constitutive Ser 267 phosphorylation complements these phenotypes and
      overcomes the necessity of CDK activity for DSB resection. The Sae2 mutations
      also cause cell-cycle-stage specific hypersensitivity to DNA damage and affect
      the balance between HR and NHEJ. These findings therefore provide a mechanistic
      basis for cell-cycle control of DSB repair and highlight the importance of
      regulating DSB resection.

PMID- 18716621
TI  - Structural insights into the evolutionary paths of oxylipin biosynthetic enzymes.
AB  - The oxylipin pathway generates not only prostaglandin-like jasmonates but also
      green leaf volatiles (GLVs), which confer characteristic aromas to fruits and
      vegetables. Although allene oxide synthase (AOS) and hydroperoxide lyase are
      atypical cytochrome P450 family members involved in the synthesis of jasmonates
      and GLVs, respectively, it is unknown how these enzymes rearrange their
      hydroperoxide substrates into different products. Here we present the crystal
      structures of Arabidopsis thaliana AOS, free and in complex with substrate or
      intermediate analogues. The structures reveal an unusual active site poised to
      control the reactivity of an epoxyallylic radical and its cation by means of
      interactions with an aromatic pi-system. Replacing the amino acid involved in
      these steps by a non-polar residue markedly reduces AOS activity and,
      unexpectedly, is both necessary and sufficient for converting AOS into a GLV
      biosynthetic enzyme. Furthermore, by combining our structural data with
      bioinformatic and biochemical analyses, we have discovered previously unknown
      hydroperoxide lyase in plant growth-promoting rhizobacteria, AOS in coral, and
      epoxyalcohol synthase in amphioxus. These results indicate that oxylipin
      biosynthetic genes were present in the last common ancestor of plants and
      animals, but were subsequently lost in all metazoan lineages except Placozoa,
      Cnidaria and Cephalochordata.

PMID- 18716620
TI  - The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML
      network.
AB  - Nuclear exclusion of the PTEN (phosphatase and tensin homologue deleted in
      chromosome 10) tumour suppressor has been associated with cancer progression.
      However, the mechanisms leading to this aberrant PTEN localization in human
      cancers are currently unknown. We have previously reported that ubiquitinylation
      of PTEN at specific lysine residues regulates its nuclear-cytoplasmic
      partitioning. Here we show that functional promyelocytic leukaemia protein (PML)
      nuclear bodies co-ordinate PTEN localization by opposing the action of a
      previously unknown PTEN-deubiquitinylating enzyme, herpesvirus-associated
      ubiquitin-specific protease (HAUSP, also known as USP7), and that the integrity
      of this molecular framework is required for PTEN to be able to enter the nucleus.
      We find that PTEN is aberrantly localized in acute promyelocytic leukaemia, in
      which PML function is disrupted by the PML-RARalpha fusion oncoprotein.
      Remarkably, treatment with drugs that trigger PML-RARalpha degradation, such as
      all-trans retinoic acid or arsenic trioxide, restore nuclear PTEN. We demonstrate
      that PML opposes the activity of HAUSP towards PTEN through a mechanism involving
      the adaptor protein DAXX (death domain-associated protein). In support of this
      paradigm, we show that HAUSP is overexpressed in human prostate cancer and is
      associated with PTEN nuclear exclusion. Thus, our results delineate a previously
      unknown PML-DAXX-HAUSP molecular network controlling PTEN deubiquitinylation and
      trafficking, which is perturbed by oncogenic cues in human cancer, in turn
      defining a new deubiquitinylation-dependent model for PTEN subcellular
      compartmentalization.

PMID- 18716622
TI  - Replication fork movement sets chromatin loop size and origin choice in mammalian
      cells.
AB  - Genome stability requires one, and only one, DNA duplication at each S phase. The
      mechanisms preventing origin firing on newly replicated DNA are well documented,
      but much less is known about the mechanisms controlling the spacing of initiation
      events(2,3), namely the completion of DNA replication. Here we show that origin
      use in Chinese hamster cells depends on both the movement of the replication
      forks and the organization of chromatin loops. We found that slowing the
      replication speed triggers the recruitment of latent origins within minutes,
      allowing the completion of S phase in a timely fashion. When slowly replicating
      cells are shifted to conditions of fast fork progression, although the decrease
      in the overall number of active origins occurs within 2 h, the cells still have
      to go through a complete cell cycle before the efficiency specific to each origin
      is restored. We observed a strict correlation between replication speed during a
      given S phase and the size of chromatin loops in the next G1 phase. Furthermore,
      we found that origins located at or near sites of anchorage of chromatin loops in
      G1 are activated preferentially in the following S phase. These data suggest a
      mechanism of origin programming in which replication speed determines the spacing
      of anchorage regions of chromatin loops, that, in turn, controls the choice of
      initiation sites.

PMID- 18716623
TI  - An intrinsic mechanism of corticogenesis from embryonic stem cells.
AB  - The cerebral cortex develops through the coordinated generation of dozens of
      neuronal subtypes, but the mechanisms involved remain unclear. Here we show that
      mouse embryonic stem cells, cultured without any morphogen but in the presence of
      a sonic hedgehog inhibitor, recapitulate in vitro the major milestones of
      cortical development, leading to the sequential generation of a diverse
      repertoire of neurons that display most salient features of genuine cortical
      pyramidal neurons. When grafted into the cerebral cortex, these neurons develop
      patterns of axonal projections corresponding to a wide range of cortical layers,
      but also to highly specific cortical areas, in particular visual and limbic
      areas, thereby demonstrating that the identity of a cortical area can be
      specified without any influence from the brain. The discovery of intrinsic
      corticogenesis sheds new light on the mechanisms of neuronal specification, and
      opens new avenues for the modelling and treatment of brain diseases.

PMID- 18716624
TI  - Modelling Myc inhibition as a cancer therapy.
AB  - Myc is a pleiotropic basic helix-loop-helix leucine zipper transcription factor
      that coordinates expression of the diverse intracellular and extracellular
      programs that together are necessary for growth and expansion of somatic cells.
      In principle, this makes inhibition of Myc an attractive pharmacological approach
      for treating diverse types of cancer. However, enthusiasm has been muted by lack
      of direct evidence that Myc inhibition would be therapeutically efficacious,
      concerns that it would induce serious side effects by inhibiting proliferation of
      normal tissues, and practical difficulties in designing Myc inhibitory drugs. We
      have modelled genetically both the therapeutic impact and the side effects of
      systemic Myc inhibition in a preclinical mouse model of Ras-induced lung
      adenocarcinoma by reversible, systemic expression of a dominant-interfering Myc
      mutant. We show that Myc inhibition triggers rapid regression of incipient and
      established lung tumours, defining an unexpected role for endogenous Myc function
      in the maintenance of Ras-dependent tumours in vivo. Systemic Myc inhibition also
      exerts profound effects on normal regenerating tissues. However, these effects
      are well tolerated over extended periods and rapidly and completely reversible.
      Our data demonstrate the feasibility of targeting Myc, a common downstream
      conduit for many oncogenic signals, as an effective, efficient and tumour
      specific cancer therapy.

PMID- 18716626
TI  - Heterochromatin links to centromeric protection by recruiting shugoshin.
AB  - The centromere of a chromosome is composed mainly of two domains, a kinetochore
      assembling core centromere and peri-centromeric heterochromatin regions. The
      crucial role of centromeric heterochromatin is still unknown, because even in
      simpler unicellular organisms such as the fission yeast Schizosaccharomyces
      pombe, the heterochromatin protein Swi6 (HP1 homologue) has several functions at
      centromeres, including silencing gene expression and recombination, enriching
      cohesin, promoting kinetochore assembly, and, ultimately, preventing erroneous
      microtubule attachment to the kinetochores. Here we show that the requirement of
      heterochromatin for mitotic chromosome segregation is largely replaced by
      forcibly enriching cohesin at centromeres in fission yeast. However, this
      enrichment of cohesin is not sufficient to replace the meiotic requirement for
      heterochromatin. We find that the heterochromatin protein Swi6 associates
      directly with meiosis-specific shugoshin Sgo1, a protector of cohesin at
      centromeres. A point mutation of Sgo1 (V242E), which abolishes the interaction
      with Swi6, impairs the centromeric localization and function of Sgo1. The forced
      centromeric localization of Sgo1 restores proper meiotic chromosome segregation
      in swi6 cells. We also show that the direct link between HP1 and shugoshin is
      conserved in human cells. Taken together, our findings suggest that the
      recruitment of shugoshin is the important primary role for centromeric
      heterochromatin in ensuring eukaryotic chromosome segregation.

PMID- 18716625
TI  - Neutralizing antibodies derived from the B cells of 1918 influenza pandemic
      survivors.
AB  - Investigation of the human antibody response to influenza virus infection has
      been largely limited to serology, with relatively little analysis at the
      molecular level. The 1918 H1N1 influenza virus pandemic was the most severe of
      the modern era. Recent work has recovered the gene sequences of this unusual
      strain, so that the 1918 pandemic virus could be reconstituted to display its
      unique virulence phenotypes. However, little is known about adaptive immunity to
      this virus. We took advantage of the 1918 virus sequencing and the resultant
      production of recombinant 1918 haemagglutinin (HA) protein antigen to
      characterize at the clonal level neutralizing antibodies induced by natural
      exposure of survivors to the 1918 pandemic virus. Here we show that of the 32
      individuals tested that were born in or before 1915, each showed seroreactivity
      with the 1918 virus, nearly 90 years after the pandemic. Seven of the eight donor
      samples tested had circulating B cells that secreted antibodies that bound the
      1918 HA. We isolated B cells from subjects and generated five monoclonal
      antibodies that showed potent neutralizing activity against 1918 virus from three
      separate donors. These antibodies also cross-reacted with the genetically similar
      HA of a 1930 swine H1N1 influenza strain, but did not cross-react with HAs of
      more contemporary human influenza viruses. The antibody genes had an unusually
      high degree of somatic mutation. The antibodies bound to the 1918 HA protein with
      high affinity, had exceptional virus-neutralizing potency and protected mice from
      lethal infection. Isolation of viruses that escaped inhibition suggested that the
      antibodies recognize classical antigenic sites on the HA surface. Thus, these
      studies demonstrate that survivors of the 1918 influenza pandemic possess highly
      functional, virus-neutralizing antibodies to this uniquely virulent virus, and
      that humans can sustain circulating B memory cells to viruses for many decades
      after exposure-well into the tenth decade of life.

PMID- 18716627
TI  - Growth in preterm infants fed either a partially hydrolyzed whey or an intact
      casein/whey preterm infant formula.
AB  - OBJECTIVE: To compare feeding tolerance, nutrient intake and growth in preterm
      infants (< or =32 weeks, < or =1750 g) fed either a standard nonhydrolyzed whey
      casein (nHWC) or a partially hydrolyzed whey (pHW) preterm infant formula. STUDY
      DESIGN: In this double-blind randomized controlled trial infants were fed either
      formula for at least 3 weeks. Intake was monitored daily, serum chemistries and
      growth weekly. Data were analyzed using analysis of covariance. RESULT: A total
      of 80 infants were enrolled, 72 completed the study. No differences were noted in
      demographic characteristics. No differences were detected in feeding tolerance,
      intakes (118+/-21 vs 119+/-14; nHWC vs pHW) or growth weight, 28+/-1.5 vs 28+/
      1.6 g per day; length, 1.0+/-0.7 vs 1.0+/-0.6 cm per week; head circumference,
      0.9+/-0.4 vs 1.0+/-0.44 cm per week). At the end of study, blood urea nitrogen
      (5.2+/-3.1 <6.7+/-2.3 mg per 100 ml, nHWC<pHW), total serum proteins (4.7+/-0.4
      >4.4+/-0.5 g per 100 ml) and albumin (2.7+/-0.3 >2.6+/-0.4 g per 100 ml)
      differed. CONCLUSION: A pHW preterm infant formula was not associated with
      improved feeding tolerance, enteral intake or growth but differences in serum
      chemistries. These are unlikely to be clinically relevant because values were
      well within normal limits for preterm infants, whereas growth was identical in
      both groups and paralleled that 'in utero'.

PMID- 18716629
TI  - Effect of parity on gestational age at delivery in multiple gestation
      pregnancies.
AB  - OBJECTIVE: To estimate the effect of parity on gestational age (GA) at birth in
      multifetal pregnancies. STUDY DESIGN: Birth data from the public-access Matched
      Multiple Birth File produced by the National Center for Health Statistics from
      1995 to 2000 were analyzed following IRB approval. GA, parity and demographic
      data were analyzed with parametric and nonparametric tests, including regression
      analysis, using SPSS. RESULT: Data from women with twin (n=316,983), triplet
      (n=11,981), and quadruplet (n=766) pregnancies were analyzed. A significantly
      higher proportion of nulliparous versus parous women were Caucasian (twins: 82
      versus 77%; triplets: 91 versus 87%) and had more than 15 years of education
      (twins: 39 versus 24%; triplets: 55 versus 39%; quadruplets: 53 versus 35%). Mean
      GA was 5.6 days longer for twins, 5.4 days longer for triplets and 6.8 days
      longer for quadruplets born to parous versus nulliparous women. Caucasian and
      African-American parous women pregnant with twins or triplets delivered their
      babies at a later GA than their nulliparous counterparts at each level of
      education. GA at delivery increased as a function of age of the mother in
      nulliparous and parous women of twins or triplets, and at every age level, parous
      women delivered their babies at a later GA. A higher proportion of nulliparous
      women delivered before 24 weeks (twins: 2.9 versus 1.2%; triplets: 5.9 versus
      2.5%; quadruplets: 8.3 versus 2.6%). The percentage of twins born at or after 32
      weeks was 84.9% for nullipara and 90.1% for parous women; for triplets,
      corresponding figures were 61.4 and 69.6%; and for quadruplets the figures were
      33.2 and 44.2%. The percentage of births at or after 36 weeks for nulliparous and
      parous women pregnant with twins was 54.8 and 63.2%, respectively. The majority
      of the gain in GA was observed between women who had no previous births and those
      who had one previous birth. In regression analysis, the effect of parity remained
      after controlling for demographic and risk factors known to affect GA.
      CONCLUSION: GA at delivery is significantly increased in parous women carrying a
      multifetal gestation after controlling for other factors that affect GA at birth.

PMID- 18716628
TI  - Role of human milk in extremely low birth weight infants' risk of necrotizing
      enterocolitis or death.
AB  - OBJECTIVE: To determine the association between human milk (HM) intake and risk
      of necrotizing enterocolitis (NEC) or death among infants 401 to 1000 g birth
      weight. STUDY DESIGN: Analysis of 1272 infants in the National Institute of Child
      Health and Human Development Neonatal Network Glutamine Trial was performed to
      determine if increasing HM intake was associated with decreased risk of NEC or
      death. HM intake was defined as the proportion of HM to total intake, to enteral
      intake and total volume over the first 14 days. Known NEC risk factors were
      included as covariates in Cox proportional hazard analyses for duration of
      survival time free of NEC. RESULT: Among study infants, 13.6% died or developed
      NEC after 14 days. The likelihood of NEC or death after 14 days was decreased by
      a factor of 0.83 (95% confidence interval, CI 0.72, 0.96) for each 10% increase
      in the proportion of total intake as HM. Each 100 ml kg(-1) increase in HM intake
      during the first 14 days was associated with decreased risk of NEC or death
      (hazard ratio, HR 0.87 (95% CI 0.77, 0.97)). There appeared to be a trend towards
      a decreased risk of NEC or death among infants who received 100% HM as a
      proportion to total enteral intake (HM plus formula), although this finding was
      not statistically significant (HR 0.85 (95% CI 0.60, 1.19)). CONCLUSION: These
      data suggest a dose-related association of HM feeding with a reduction of risk of
      NEC or death after the first 2 weeks of life among extremely low birth weight
      infants.

PMID- 18716630
TI  - Mutations of RNA polymerase II activate key genes of the nucleoside triphosphate
      biosynthetic pathways.
AB  - The yeast URA2 gene, encoding the rate-limiting enzyme of UTP biosynthesis, is
      transcriptionally activated by UTP shortage. In contrast to other genes of the
      UTP pathway, this activation is not governed by the Ppr1 activator. Moreover, it
      is not due to an increased recruitment of RNA polymerase II at the URA2 promoter,
      but to its much more effective progression beyond the URA2 mRNA start site(s).
      Regulatory mutants constitutively expressing URA2 resulted from cis-acting
      deletions upstream of the transcription initiator region, or from amino-acid
      replacements altering the RNA polymerase II Switch 1 loop domain, such as rpb1
      L1397S. These two mutation classes allowed RNA polymerase to progress downstream
      of the URA2 mRNA start site(s). rpb1-L1397S had similar effects on IMD2 (IMP
      dehydrogenase) and URA8 (CTP synthase), and thus specifically activated the rate
      limiting steps of UTP, GTP and CTP biosynthesis. These data suggest that the
      Switch 1 loop of RNA polymerase II, located at the downstream end of the
      transcription bubble, may operate as a specific sensor of the nucleoside
      triphosphates available for transcription.

PMID- 18716631
TI  - Nuclear receptor signalling in dendritic cells connects lipids, the genome and
      immune function.
AB  - Dendritic cells (DCs) are sentinels of the immune system and represent a
      heterogeneous cell population. The existence of distinct DC subsets is due to
      their inherent plasticity and to the changing microenvironment modulating their
      immunological properties. Numerous signalling pathways have impacts on DCs. It
      appears that besides cytokines/chemokines, lipid mediators also have profound
      effects on the immunogenicity of DCs. Some of these lipid mediators exert an
      effect through nuclear hormone receptors. Interestingly, more recent findings
      suggest that DCs are able to convert precursors to active hormones, ligands for
      nuclear receptors. Some of these DC-derived lipids, in particular retinoic acid
      (RA), have a central function in shaping T-cell development and effector
      functions. In this review, we summarize and highlight the function of a set of
      nuclear receptors (PPARgamma, RA receptor, vitamin D receptor and glucocorticoid
      receptor) in DC biology. Defining the contribution of nuclear hormone receptor
      signalling in DCs can help one to understand the regulatory logic of lipid
      signalling and allow the exploitation of their potential for therapeutic
      intervention in various immunological diseases.

PMID- 18716632
TI  - Toxicology and carcinogenesis studies of formamide (Cas No. 75-12-7) in F344/N
      rats and B6C3F1 mice (gavage studies).
AB  - Formamide is used as a softener for paper, gums, and animal glues; as an ionizing
      solvent; and in the manufacture of formic esters and hydrocyanic acid. Formamide
      was nominated for reproductive and genetic toxicity evaluation by the
      Environmental Defense Fund and for carcinogenicity evaluation by the National
      Cancer Institute because of the potential for human exposure associated with its
      widespread industrial use, the absence of data adequately characterizing its
      potential for reproductive and genetic toxicity, and the fact that acetamide, a
      compound structurally related to form-amide, is hepatocarcinogenic in rats when
      administered in feed. Male and female F344/N rats and B6C3F1 mice were
      administered formamide (approximately 100% pure) in deionized water by gavage for
      2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in
      Salmonella typhimurium and Escherichia coli, Drosophila melanogaster, and mouse
      peripheral blood erythrocytes. 3-MONTH STUDY IN RATS: Groups of 10 male and 10
      female rats were administered 0, 10, 20, 40, 80, or 160 mg formamide/kg body
      weight in deionized water by gavage, 5 days per week for 14 weeks. Additional
      groups of 10 male and 10 female rats (clinical pathology study) and five male and
      five female rats (plasma concentration study) were administered the same doses, 5
      days per week for up to 14 weeks. All core study rats survived to the end of the
      study. Mean body weights of females in the 40 mg/kg group and males and females
      in the 80 and 160 mg/kg groups were significantly less than those of the vehicle
      controls. On day 23 and at week 14, there was a dose-related increase in the
      erythron, evidenced by increases in hematocrit values, hemoglobin concentrations,
      and erythrocyte counts. The incidences of degeneration of the germinal epithelium
      of the testes and epididymis were significantly increased in 160 mg/kg males. 3
      MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were administered 0,
      10, 20, 40, 80, or 160 mg formamide/kg body weight in deionized water by gavage,
      5 days per week for 14 weeks. Additional groups of five male and five female mice
      (plasma concentration study) were administered the same doses, 5 days per week
      for 14 weeks. All mice survived to the end of the study. Final mean body weights
      of the 80 and 160 mg/kg males and mean body weight gains of 40, 80, and 160 mg/kg
      males were significantly less than those of the vehicle controls. Dosed females
      differed significantly from vehicle controls in the relative amount of time spent
      in the estrous stages. All 160 mg/kg males had abnormal residual bodies in the
      testes. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were
      administered 0, 20, 40, or 80 mg formamide/kg body weight, 5 days per week for
      104 to 105 weeks in deionized water by gavage. Survival of all dosed groups of
      rats was similar to that of the vehicle controls. Mean body weights of 80 mg/kg
      males were less than those of the vehicle controls throughout most of the study.
      Mean body weights of 40 and 80 mg/kg females were somewhat less than those of the
      vehicle controls during the second year of the study. A significant increase in
      the incidence of bone marrow hyperplasia occurred in 80 mg/kg males. No neoplasms
      were attributed to exposure to formamide. 2-YEAR STUDY IN MICE: Groups of 50 male
      and 50 female mice were administered 0, 20, 40, or 80 mg formamide/kg body
      weight, 5 days per week for 104 to 105 weeks in deionized water by gavage.
      Survival of all dosed groups of mice was similar to that of the vehicle controls.
      Mean body weights of 80 mg/kg males and females were generally less than those of
      the vehicle controls throughout the study; mean body weights of 40 mg/kg females
      were generally less after week 13 of the study. The incidences of hemangiosarcoma
      of the liver occurred with a positive trend in males, and the incidences were
      significantly increased in the 40 and 80 mg/kg groups. The incidence of
      hepatocellular adenoma or carcinoma (combined) in 80 mg/kg females was
      significantly increased. The incidences of mineralization of the testicular
      arteries and testicular tunic were significantly increased in 80 mg/kg males. The
      incidence of hematopoietic cell proliferation of the spleen was significantly
      increased in 80 mg/kg males. GENETIC TOXICOLOGY: Formamide gave no evidence for
      mutagenicity in a series of short-term assays. In three independent Ames assays,
      formamide was not mutagenic in any of several strains of S. typhimurium tested
      with and without rat or hamster liver S9 activation enzymes or in E. coli strain
      WP uvrA pKM101 tested with and without 10% rat liver S9. Negative results were
      obtained in a test for induction of sex-linked recessive lethal mutations in germ
      cells of male D. melanogaster treated with formamide either by feeding or
      injection. Formamide did not induce increases in micronucleated erythrocytes in
      male or female mice treated by gavage for 3 months. CONCLUSIONS: Under the
      conditions of these 2-year gavage studies, there was no evidence of carcinogenic
      activity of form-amide in male or female F344/N rats administered 20, 40, or 80
      mg/kg. There was clear evidence of carcinogenic activity of formamide in male
      B6C3F1 mice based on increased incidences of hemangiosarcoma of the liver. There
      was equivocal evidence of carcinogenic activity of formamide in female B6C3F1
      mice based on increased incidences of hepatocellular adenoma or carcinoma
      (combined). An increased incidence of bone marrow hyperplasia occurred in male
      rats. Mineralization of the testicular arteries and tunic and hematopoietic cell
      proliferation of the spleen in male mice were also associated with administration
      of formamide.

PMID- 18716633
TI  - Toxicology and carcinogenesis studies of sodium dichromate dihydrate (Cas No.
      7789-12-0) in F344/N rats and B6C3F1 mice (drinking water studies).
AB  - Sodium dichromate dihydrate is one of a number of inorganic compounds containing
      hexavalent chromium (Cr VI) found in drinking water source supplies as a
      contaminant resulting from various industrial processes including electroplating
      operations, leather tanning, and textile manufacturing. Because of the lack of
      adequate experimental data on the toxicity and carcinogenicity of hexavalent
      chromium ingested orally and because hexavalent chromium has been found in
      drinking water source supplies, the California Congressional Delegation, the
      California Environmental Protection Agency, and the California Department of
      Health Services nominated hexavalent chromium to the National Toxicology Program
      for study. Results of 3 month toxicity studies in F344/N rats and B6C3F1, BALB/c,
      and am3-C57BL/6 mice were reported earlier in NTP Toxicity Report 72. In the
      current study, male and female F344/N rats and B6C3F1 mice were exposed to sodium
      dichromate dihydrate (greater than 99.7% pure) in drinking water for 2 years. 2
      YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to drinking
      water containing 0, 14.3, 57.3, 172, or 516 mg/L sodium dichromate dihydrate
      (equivalent to 0, 5, 20, 60, or 180 mg/L chromium) for 2 years (equivalent to
      average daily doses of approximately 0.6, 2.2, 6, or 17 mg sodium dichromate
      dihydrate/kg body weight for males and 0.7, 2.7, 7, or 20 mg/kg for females).
      Survival of exposed groups was similar to that of the control groups. Mean body
      weights of 516 mg/L males and females were less than those of the controls
      throughout the study. The lower body weights were partly attributed to poor
      palatability of the dosed water and consequent reductions in water consumption.
      Water consumption by 172 and 516 mg/L rats was less than that by the controls
      throughout the study. Exposure to sodium dichromate dihydrate caused a microcytic
      hypochromic anemia in rats that ameliorated with time. Exposure to sodium
      dichromate dihydrate resulted in the development of neoplasms of the squamous
      epithelium that lines the oral mucosa and tongue. The incidences of squamous cell
      carcinoma in the oral mucosa of 516 mg/L male and female rats were significantly
      greater than those in the controls. The incidence in 172 mg/L females exceeded
      the historical control ranges for drinking water studies and for all routes of
      administration. The incidences of squamous cell papilloma or squamous cell
      carcinoma (combined) of the oral mucosa or tongue of 516 mg/L male and female
      rats were significantly greater than those in the controls. Exposure
      concentration-related nonneoplastic liver lesions were observed in males and
      females exposed to 57.3 mg/L or greater. These included histiocytic cellular
      infiltration, chronic inflammation, fatty change (females), basophilic focus
      (males), and clear cell focus (females). Increased incidences of histiocytic
      cellular infiltration also occurred in the small intestine (duodenum), mesenteric
      lymph node, and pancreatic lymph node of males and/or females exposed to 57.3
      mg/L or greater. 2-YEAR STUDY IN MICE: Groups of 50 male mice were exposed to
      drinking water containing 0, 14.3, 28.6, 85.7, or 257.4 mg/L sodium dichromate
      dihydrate (equivalent to 0, 5, 10, 30, or 90 mg/L chromium) for 2 years
      (equivalent to average daily doses of approximately 1.1, 2.6, 7, or 17 mg sodium
      dichromate dihydrate/kg body weight). Groups of 50 female mice were exposed to
      drinking water containing 0, 14.3, 57.3, 172, or 516 mg/L sodium dichromate
      dihydrate (equivalent to 0, 5, 20, 60, or 180 mg/L chromium) for 2 years
      (equivalent to average daily doses of approximately 1.1, 3.9, 9, or 25 mg/kg).
      Survival of exposed groups was similar to that of the control groups. Mean body
      weights of 257.4 mg/L males were less than those of controls from months 2
      through 6 of the study, but by the end of the study, the mean body weight of
      257.4 mg/L males was only slightly less than that of the control group. Mean body
      weights of 172 mg/L females were less than those of the controls from months 3
      through 12 of the study, and mean body weights of 516 mg/L females were less than
      those of the controls from month 2 until the end of the study. By the end of the
      study, the mean body weight of 172 mg/L females was 8% less than that of the
      controls, and the mean body weight of 516 mg/L females was 15% less than that of
      the controls. The lower body weights were partly attributed to poor palatability
      of the dosed water and consequent reductions in water consumption. Water
      consumption by 85.7 and 257.4 mg/L males and 172 and 516 mg/L females was less
      than that by the controls throughout the study. A treatment-related microcytosis
      occurred in exposed mice; the mice were less affected than the rats. The
      incidences of neoplasms of the small intestine (duodenum, jejunum, or ileum) were
      increased in exposed groups of male and female mice. The incidences of adenoma of
      the duodenum in 257.4 mg/L males and 172 and 516 mg/L females were significantly
      greater than those in the controls. The incidence of carcinoma of the duodenum
      was significantly increased in 516 mg/L females. The incidence of adenoma of the
      jejunum in 516 mg/L females was significantly increased compared to that in the
      controls. When the incidences of adenoma and carcinoma were combined for all
      sites of the small intestine, the incidences were significantly increased in 85.7
      and 257.4 mg/L males and 172 and 516 mg/L females compared to those in the
      controls. The incidences in 57.3 mg/L females exceeded the historical control
      ranges for drinking water studies and for all routes of administration. The
      incidences of diffuse epithelial hyperplasia were significantly increased in the
      duodenum of all exposed groups of male and female mice. The incidences of
      histiocytic cellular infiltration were significantly increased in the duodenum of
      85.7 and 257.4 mg/L males and in 172 and 516 mg/L females. In the jejunum, the
      incidences of diffuse epithelial hyperplasia and histiocytic cellular
      infiltration were significantly increased in 516 mg/L females. The incidences of
      histiocytic cellular infiltration of the liver in all exposed groups of females,
      of the mesenteric lymph node in all exposed groups of males and females, and of
      the pancreatic lymph node of 85.7 and 257.4 mg/L males and 172 and 516 mg/L
      females were significantly increased. Tissue distribution studies showed that
      total chromium concentrations tended to increase with increasing exposure
      concentration and duration of exposure. CONCLUSIONS: Under the conditions of
      these 2-year drinking water studies, there was clear evidence of carcinogenic
      activity of sodium dichromate dihydrate in male and female F344/N rats based on
      increased incidences of squamous cell neoplasms of the oral cavity. There was
      clear evidence of carcinogenic activity of sodium dichromate dihydrate in male
      and female B6C3F1 mice based on increased incidences of neoplasms of the small
      intestine (duodenum, jejunum, or ileum). Exposure to sodium dichromate dihydrate
      resulted in histiocytic cellular infiltration in the liver, small intestine, and
      pancreatic and mesenteric lymph nodes of rats and mice and diffuse epithelial
      hyperplasia in the small intestine of male and female mice.

PMID- 18716634
TI  - Elimination of conjugate image for holograms using a resolution redistribution
      optical system.
AB  - A technique to alter the ratio of the horizontal and vertical resolution of a
      spatial light modulator has been proposed. This technique increases the
      horizontal resolution by a factor of K and decreases the vertical resolution by a
      factor of 1/K. The proposed technique increases the horizontal viewing angle by a
      factor of approximately K, although a conjugate image appeared. In the present
      study, the resolution redistribution technique is modified to eliminate the
      conjugate image. The height of a horizontal slit placed on the Fourier plane of a
      4 f imaging system used for the resolution redistribution system is reduced by
      half. The horizontal resolution becomes K times larger, and the vertical
      resolution becomes 1/2K times smaller. The improved technique generates only the
      object wave. We demonstrated fourfold enlargement of the horizontal resolution to
      increase the horizontal viewing angle by approximately four times without
      generating the conjugate image.

PMID- 18716635
TI  - Simultaneous estimation of aerosol cloud concentration and spectral backscatter
      from multiple-wavelength lidar data.
AB  - We present a sequential algorithm for estimating both concentration dependence on
      range and time and backscatter coefficient spectral dependence of optically thin
      localized atmospheric aerosols using data from rapidly tuned lidar. The range
      dependence of the aerosol is modeled as an expansion of the concentration in an
      orthonormal basis set whose coefficients carry the time dependence. Two
      estimators are run in parallel: a Kalman filter for the concentration range and
      time dependence and a maximum-likelihood estimator for the aerosol backscatter
      wavelength and time dependence. These two estimators exchange information
      continuously over the data-processing stream. The state model parameters of the
      Kalman filter are also estimated sequentially together with the concentration and
      backscatter. Lidar data collected prior to the aerosol release are used to
      estimate the ambient lidar return. The approach is illustrated on atmospheric
      backscatter long-wave infrared (CO2) lidar data.

PMID- 18716636
TI  - Step method: a new synthesis method for the design of optical filters with
      intermediate refractive indices.
AB  - We propose a new synthesis method for the design of multilayer optical filters
      with intermediate refractive indices, the step method. This method consists in
      adding infinitesimally small index steps in the index profile at optimal
      positions and then reoptimizing the thickness and the refractive index of the
      layers. Application of the method to the design of an antireflective coating, a
      low-pass edge filter, and an immersed polarizing beam splitter shows that it
      provides interesting solutions, even in the absence of a proper starting design.
      The formalism developed for the method also serves to demonstrate that the
      optimal filter consists of either homogeneous layers that maximize the effective
      refractive index contrast, or of graded-index layers.

PMID- 18716637
TI  - Improved neural network based scene-adaptive nonuniformity correction method for
      infrared focal plane arrays.
AB  - An improved scene-adaptive nonuniformity correction (NUC) algorithm for infrared
      focal plane arrays (IRFPAs) is proposed. This method simultaneously estimates the
      infrared detectors' parameters and eliminates the nonuniformity causing fixed
      pattern noise (FPN) by using a neural network (NN) approach. In the learning
      process of neuron parameter estimation, the traditional LMS algorithm is
      substituted with the newly presented variable step size (VSS) normalized least
      mean square (NLMS) based adaptive filtering algorithm, which yields faster
      convergence, smaller misadjustment, and lower computational cost. In addition, a
      new NN structure is designed to estimate the desired target value, which promotes
      the calibration precision considerably. The proposed NUC method reaches high
      correction performance, which is validated by the experimental results
      quantitatively tested with a simulative testing sequence and a real infrared
      image sequence.

PMID- 18716638
TI  - Laser offset-frequency locking up to 20 GHz using a low-frequency electrical
      filter technique.
AB  - A simple, easy-to-implement, and robust technique is reported to offset lock two
      semiconductor lasers with a frequency difference easily adjustable up to a couple
      of tens of gigahertz (10 and 19 GHz experimentally demonstrated). The proposed
      scheme essentially makes use of low-frequency control electronics and may be
      implemented with any type of single mode semiconductor laser, without any
      requirement for the laser linewidth. The technique is shown to be very similar to
      the wavelength modulation spectroscopy method commonly used for laser
      stabilization onto molecular absorption lines, as demonstrated by experimental
      results obtained using 935 nm laser diodes.

PMID- 18716639
TI  - Linear and nonlinear optical characteristics of ZnO-SiO2 nanocomposites.
AB  - We present the spectral and nonlinear optical properties of ZnO-SiO2
      nanocomposites prepared by colloidal chemical synthesis. Obvious enhancement of
      ultraviolet (UV) emission of the samples is observed, and the strongest UV
      emission of a typical ZnO-SiO2 nanocomposite is over three times stronger than
      that of pure ZnO. The nonlinearity of the silica colloid is low, and its
      nonlinear response can be improved by making composites with ZnO. These
      nanocomposites show self-defocusing nonlinearity and good nonlinear absorption
      behavior. The observed nonlinear absorption is explained through two photon
      absorption followed by weak free carrier absorption and nonlinear scattering. The
      nonlinear refractive index and the nonlinear absorption increase with increasing
      ZnO volume fraction and can be attributed to the enhancement of exciton
      oscillator strength. ZnO-SiO2 is a potential nanocomposite material for the UV
      light emission and for the development of nonlinear optical devices with a
      relatively small limiting threshold.

PMID- 18716640
TI  - Diode-laser-based near-resonantly enhanced flow visualization in shock tunnels.
AB  - Two new near-resonantly enhanced flow visualization techniques suitable for
      hypersonic low-density flows in shock or arc tunnels have been developed using
      seeded lithium (Li) metal as the refractivity-enhancing species. Two
      semiconductor lasers, single-longitudinal-mode and multimode, are compared with
      respect to their suitability as light sources for the technique. Transient wake
      flow structures around a cylinder and a model of a planetary entry vehicle are
      visualized to demonstrate the capabilities of this comparatively inexpensive and
      simple visualization system. The images show flow features which are undetectable
      with conventional schlieren, shadowgraph, or interferometry techniques.
      Furthermore, the effect of density inhomogeneities along the line-of-sight
      outside the region of interest can be reduced by enhancing the refractivity only
      in selected parts of the flowfield.

PMID- 18716641
TI  - Imaging polarimetry of glass buildings: why do vertical glass surfaces attract
      polarotactic insects?
AB  - Recently it was observed that the Hydropsyche pellucidula caddis flies swarm near
      sunset at the vertical glass surfaces of buildings standing on the bank of the
      Danube river in Budapest, Hungary. These aquatic insects emerge from the Danube
      and are lured to dark vertical panes of glass, where they swarm, land, copulate,
      and remain for hours. It was also shown that ovipositing H. pellucidula caddis
      flies are attracted to highly and horizontally polarized light stimulating their
      ventral eye region and thus have positive polarotaxis. The attraction of these
      aquatic insects to vertical reflectors is surprising, because after their aerial
      swarming, they must return to the horizontal surface of water bodies from which
      they emerge and at which they lay their eggs. Our aim is to answer the questions:
      Why are flying polarotactic caddis flies attracted to vertical glass surfaces?
      And why do these aquatic insects remain on vertical panes of glass after landing?
      We propose that both questions can be partly explained by the reflection
      polarization characteristics of vertical glass surfaces and the positive
      polarotaxis of caddis flies. We measured the reflection-polarization patterns of
      shady and sunlit, black and white vertical glass surfaces from different
      directions of view under clear and overcast skies by imaging polarimetry in the
      red, green, and blue parts of the spectrum. Using these polarization patterns we
      determined which areas of the investigated glass surfaces are sensed as water by
      a hypothetical polarotactic insect facing and flying toward or landed on a
      vertical pane of glass. Our results strongly support the mentioned proposition.
      The main optical characteristics of "green," that is, environmentally friendly,
      buildings, considering the protection of polarotactic aquatic insects, are also
      discussed. Such "green" buildings possess features that attract only a small
      number of polarotactic aquatic insects when standing in the vicinity of fresh
      waters. Since vertical glass panes of buildings are abundant in the man-made
      optical environment, and polarotactic aquatic insects are spread worldwide, our
      results are of general interest in the visual and behavioral ecology of aquatic
      insects.

PMID- 18716642
TI  - Wavelength-dependent diffraction patterns from a liquid crystal display.
AB  - Liquid crystal displays (LCDs) are invaluable for a variety of optical
      applications, including the encoding of programmable diffractive optical
      elements. The pixel structure in these devices produces a set of diffracted
      orders of which the central order is the strongest. In most devices that we have
      examined, the intensity distribution of the diffraction pattern is independent of
      the wavelength of the illuminating light. Recently we have been examining the
      performance of LCDs having very small pixel sizes. We compare results for two
      devices from the same manufacturer. One of them exhibits the normal behavior. For
      the other, we find surprisingly strong wavelength dependence. The diffraction
      pattern varies from having most of the energy in the zero order for long
      wavelengths to having the energy distributed among 50-60 orders as the wavelength
      decreases. We attribute this behavior to a phase structure over each pixel. We
      analyze this behavior using a simple two-dimensional model that qualitatively
      explains the phenomenon. These results can be viewed in two ways--on the positive
      side this behavior might lead to optical logic or fan-out applications. On the
      negative side, there is less intensity available in the normally used zero order.

PMID- 18716643
TI  - Developing an optimum computer-designed multispectral system comprising a
      monochrome CCD camera and a liquid-crystal tunable filter.
AB  - In a previous work [J. Opt. Soc. Am. A24, 942 (2007)JOAOD60740
      323210.1364/JOSAA.24.000942] we made a complete theoretical and computational
      study of the influence of several parameters on the behavior of a planned
      multispectral system for imaging skylight, including the number of sensors and
      the spectral estimation algorithm. Here we follow up this study by using all the
      information obtained in the computational simulations to implement a real
      multispectral imaging system based on a monochrome CCD camera and a liquid
      crystal tunable filter (LCTF). We were able to construct the optimum Gaussian
      sensors found in the simulations by adjusting the exposure times of some of the
      transmittance modes of the LCTF, hence obtaining really accurate spectral
      estimations of skylight with only a few optimum sensors.

PMID- 18716644
TI  - Full-field retardation measurement of a liquid crystal cell with a phase shift
      polariscope.
AB  - A novel method is developed to provide high-resolution, full-field retardation
      measurement of the liquid crystal cell using a phase shift polariscope. The phase
      retardation of a liquid crystal cell is influenced by its thickness, and hence an
      accurate measurement of the full field retardation gives the thickness
      distribution of the liquid crystal cell. In the phase shift polariscope, phase
      shift images obtained by rotating the analyzer are recorded and analyzed to
      obtain the phase retardation and hence the whole field thickness distribution of
      the liquid crystal cells. The results obtained using this method are compared
      with those using a commercial pointwise sensor with good agreement. The proposed
      method yields accurate and repeatable full-field cell gap measurement of the
      liquid crystal cell with a simple experimental setup.

PMID- 18716645
TI  - Verdet constant dispersion measurement using polarization-stepping techniques.
AB  - We present a novel method for measuring the Verdet constant dispersion. The
      proposed method involves spectral polarimetric measurements using three (or more)
      polarization steps. The procedure has formal similarity with the phase-shifting
      interferometry (PSI). Thus the Verdet constant in the desired spectral range can
      be retrieved using well-known PSI algorithms. Validation experiments are
      presented.

PMID- 18716646
TI  - Optical authentication method using a three-dimensional phase object with various
      wavelength readouts.
AB  - An optical system for authentication using a 3D (3D) random phase object with
      various wavelength readouts is proposed. The 3D phase object without surface
      modulation is secure when the scattering is strong enough because it prevents
      from the interferometric measurement. The identification is implemented by the
      correlation between a measured speckle pattern of the 3D phase object and stored
      speckle patterns. For accurate identification, two speckle patterns of the 3D
      object obtained by illuminating two wavelengths are used. Experimental
      demonstrations and numerical evaluations of wavelength selectivity are presented.

PMID- 18716647
TI  - Scanning flow cytometer modified to distinguish phytoplankton cells from their
      effective size, effective refractive index, depolarization, and fluorescence.
AB  - A laser flow cytometer based on scanning flow cytometry has been assembled. The
      unpolarized and linearly polarized light-scattering profiles, as well as the side
      emitted light in different spectral bands, were measured, allowing the
      simultaneous and real-time determination of the effective size and the effective
      refractive index of each spherelike particle. Additionally, each particle could
      be identified from depolarization and fluorescence measured simultaneously. The
      tests with aqueous samples of polystyrene spheres, fluorescent or nonfluorescent,
      and phytoplankton cells demonstrate that the system is able to retrieve size and
      refractive index with an accuracy of 1% and that the depolarization and
      fluorescence measurements allow the classification of particles otherwise
      indistinguishable.

PMID- 18716648
TI  - Compact and miniature snapshot imaging polarimeter.
AB  - We present and demonstrate a compact and miniature snapshot imaging polarimeter
      camera; it is anticipated that such a camera can be scaled down to less than 1.5
      cm. Two Savart plates are used at the pupil plane to generate multiple fringes to
      encode the full Stokes vector in a single image. A geometric ray model is
      developed to explain the system. The numerical simulation based on this model is
      presented. Finally, the validity of the device is demonstrated by showing
      experimental results.

PMID- 18716649
TI  - South Pole Telescope optics.
AB  - The South Pole Telescope is a 10 m diameter, wide-field, offset Gregorian
      telescope with a 966-pixel, millimeter-wave, bolometer array receiver. The
      telescope has an unusual optical system with a cold stop around the secondary.
      The design emphasizes low scattering and low background loading. All the optical
      components except the primary are cold, and the entire beam from prime focus to
      the detectors is surrounded by cold absorber.

PMID- 18716650
TI  - The Hertz/VPM polarimeter: design and first light observations.
AB  - We present first results of Hertz/VPM, the first submillimeter polarimeter
      employing the dual Variable-delay Polarization Modulator (dual-VPM). This device
      differs from previously used polarization modulators in that it operates in
      translation, rather than mechanical rotation. We discuss the basic theory behind
      this device and its potential advantages over the commonly used half-wave plate.
      The dual-VPM was tested both at the Submillimeter Telescope Observatory and in
      the laboratory. In each case we present a detailed description of the setup. We
      discovered that properties of the VPM wire grids (diameter and spacing) caused
      behavior that differs from theoretical predictions for ideal wire grid
      performance. By modifying the polarimeter settings to compensate for this
      behavior, we found that the dual-VPM system is robust, operating with high
      efficiency and low instrumental polarization. This device is well suited for air-
      and space-borne applications.

PMID- 18716651
TI  - Operation and investigation of a tilted bottom cavity for pyrgeometer
      characterizations.
AB  - A new cavity for pyrgeometer characterizations has been built at the Infrared
      Radiometry Section of the World Radiation Center (WRC-IRS) at PMOD/WRC. The
      calculated effective emissivity of 0.99993+/-0.00033 was obtained from Monte
      Carlo simulations taking into account the geometry and the measured temperature
      distributions of the cavity. The cavity is operated in a temperature range of -30
      degrees C to +30 degrees C and is initially flushed with nitrogen to reduce the
      relative humidity in the cavity. The estimated uncertainties of retrieved
      pyrgeometer parameters k1, k2, and k3 are +/-0.024, +/-0.0008, and +/-0.03,
      respectively. The relative uncertainty of pyrgeometer sensitivity C is 0.8%. The
      comparison with the cavity used since 1995 at PMOD/WRC gave average differences
      of 0.005, 0.00026, and 0.08 for k1, k2, and k3, respectively. The pyrgeometer
      sensitivity retrieved with the new cavity is on average 1.0% higher than with the
      original cavity.

PMID- 18716652
TI  - Methods of advanced wound management for care of combined traumatic and chemical
      warfare injuries.
AB  - OBJECTIVE: Chemical warfare agents are potential threats to military personnel
      and civilians. The potential for associated traumatic injuries is significant.
      Damage control surgery could expose medical personnel to agents contaminating the
      wounds. The objectives of this study were to demonstrate efficacy of surgical
      decontamination and assess exposure risk to attending personnel. METHODS:
      Weanling pigs were randomly assigned to 2 of 4 debridement tools (scalpel, Bovie
      knife, Fugo Blade, and Versajet Hydrosurgery System). Penetrating traumatic
      wounds were created over the shoulder and thigh and then exposed to liquid sulfur
      mustard (HD) for 60 minutes. Excisional debridement of the injuries was performed
      while vapors over each site were collected. Gas chromatography was used to
      measure HD in samples of collected vapors. Unbound HD was quantified in
      presurgical wound swabs, excised tissues, and peripheral tissue biopsies
      following solvent extraction. RESULTS: Excisional debridement produced agent-free
      wound beds (surgical decontamination). A significant amount of HD vapor was
      detected above the surgical fields with each tool. Apart from the Versajet
      producing significantly lower levels of HD detected over thigh wounds compared
      with those treated using the scalpel, there were no differences in the amount of
      agent detected among the tools. All measured levels significantly exceeded
      established safety limits. Vesicating levels of unbound HD were extracted from
      excised tissue. There was no measured lateral spreading of HD beyond the surgical
      margins. CONCLUSIONS: There is significant occupational exposure risk to HD
      during surgical procedures designed to stabilize agent-contaminated wounds. If
      appropriate protective measures are taken, surgical decontamination is both
      effective and safe.

PMID- 18716653
TI  - A prospective study of burn trauma in adults at the university of calabar
      teaching hospital, calabar (South eastern Nigeria).
AB  - BACKGROUND: Burn injuries are among the most devastating injuries seen in the
      emergency units. The epidemiology of this injury varies from one part of the
      world to another. This is a 3-year report in an attempt to provide information on
      the current epidemiology of burns in this center. METHOD: Patients admitted into
      the University of Calabar Teaching Hospital, with burn injuries were
      prospectively studied between February 2005 and January 2008. RESULTS: The 59
      patients (33 males and 26 females) accounted for 3.7% of trauma patients and
      their ages ranged from 15 to 70 years (mean 29.4 years). Flame burn was the
      commonest injury seen in 48 (81.3%) patients because of petrol and kerosene,
      whereas chemical burn that involved 7 (11.9%) patients ranked second. Morbidity
      included burns wound infection in 13 (22%) patients and contractures in 6 (10.2%)
      patients. The outcome was fatal in 15 (25.4%) patients. CONCLUSION: The
      establishment of burn support groups dedicated to publicity on prevention based
      on areas of risk highlighted in this study and provision of financial aid as well
      as provision of modern burn care facilities would improve outcome.

PMID- 18716654
TI  - Seeing without Seeing? Degraded Conscious Vision in a Blindsight Patient.
AB  - Blindsight patients, whose primary visual cortex is lesioned, exhibit preserved
      ability to discriminate visual stimuli presented in their "blind" field, yet
      report no visual awareness hereof. Blindsight is generally studied in
      experimental investigations of single patients, as very few patients have been
      given this "diagnosis". In our single case study of patient GR, we ask whether
      blindsight is best described as unconscious vision, or rather as conscious, yet
      severely degraded vision. In experiment 1 and 2, we successfully replicate the
      typical findings of previous studies on blindsight. The third experiment,
      however, suggests that GR's ability to discriminate amongst visual stimuli does
      not reflect unconscious vision, but rather degraded, yet conscious vision. As our
      finding results from using a method for obtaining subjective reports that has not
      previously used in blindsight studies (but validated in studies of healthy
      subjects and other patients with brain injury), our results call for a
      reconsideration of blindsight, and, arguably also of many previous studies of
      unconscious perception in healthy subjects.

PMID- 18716656
TI  - GABA(A) receptor-mediated acceleration of aging-associated memory decline in
      APP/PS1 mice and its pharmacological treatment by picrotoxin.
AB  - Advanced age and mutations in the genes encoding amyloid precursor protein (APP)
      and presenilin (PS1) are two serious risk factors for Alzheimer's disease (AD).
      Finding common pathogenic changes originating from these risks may lead to a new
      therapeutic strategy. We observed a decline in memory performance and reduction
      in hippocampal long-term potentiation (LTP) in both mature adult (9-15 months)
      transgenic APP/PS1 mice and old (19-25 months) non-transgenic (nonTg) mice. By
      contrast, in the presence of bicuculline, a GABA(A) receptor antagonist, LTP in
      adult APP/PS1 mice and old nonTg mice was larger than that in adult nonTg mice.
      The increased LTP levels in bicuculline-treated slices suggested that GABA(A)
      receptor-mediated inhibition in adult APP/PS1 and old nonTg mice was upregulated.
      Assuming that enhanced inhibition of LTP mediates memory decline in APP/PS1 mice,
      we rescued memory deficits in adult APP/PS1 mice by treating them with another
      GABA(A) receptor antagonist, picrotoxin (PTX), at a non-epileptic dose for 10
      days. Among the saline vehicle-treated groups, substantially higher levels of
      synaptic proteins such as GABA(A) receptor alpha1 subunit, PSD95, and NR2B were
      observed in APP/PS1 mice than in nonTg control mice. This difference was
      insignificant among PTX-treated groups, suggesting that memory decline in APP/PS1
      mice may result from changes in synaptic protein levels through homeostatic
      mechanisms. Several independent studies reported previously in aged rodents both
      an increased level of GABA(A) receptor alpha1 subunit and improvement of
      cognitive functions by long term GABA(A) receptor antagonist treatment.
      Therefore, reduced LTP linked to enhanced GABA(A) receptor-mediated inhibition
      may be triggered by aging and may be accelerated by familial AD-linked gene
      products like Abeta and mutant PS1, leading to cognitive decline that is
      pharmacologically treatable at least at this stage of disease progression in
      mice.

PMID- 18716655
TI  - Administration of M. leprae Hsp65 interferes with the murine lupus progression.
AB  - The heat shock protein [Hsp] family guides several steps during protein
      synthesis, are abundant in prokaryotic and eukaryotic cells, and are highly
      conserved during evolution. The Hsp60 family is involved in assembly and
      transport of proteins, and is expressed at very high levels during autoimmunity
      or autoinflammatory phenomena. Here, the pathophysiological role of the wild type
      [WT] and the point mutated K(409)A recombinant Hsp65 of M. leprae in an animal
      model of Systemic Lupus Erythematosus [SLE] was evaluated in vivo using the
      genetically homogeneous [NZBxNZW]F(1) mice. Anti-DNA and anti-Hsp65 antibodies
      responsiveness was individually measured during the animal's life span, and the
      mean survival time [MST] was determined. The treatment with WT abbreviates the
      MST in 46%, when compared to non-treated mice [p<0.001]. An increase in the
      IgG2a/IgG1 anti-DNA antibodies ratio was also observed in animals injected with
      the WT Hsp65. Incubation of BALB/c macrophages with F(1) serum from WT treated
      mice resulted in acute cell necrosis; treatment of these cells with serum from
      K(409)A treated mice did not cause any toxic effect. Moreover, the involvement of
      WT correlates with age and is dose-dependent. Our data suggest that Hsp65 may be
      a central molecule intervening in the progression of the SLE, and that the point
      mutated K(409)A recombinant immunogenic molecule, that counteracts the
      deleterious effect of WT, may act mitigating and delaying the development of SLE
      in treated mice. This study gives new insights into the general biological role
      of Hsp and the significant impact of environmental factors during the
      pathogenesis of this autoimmune process.

PMID- 18716657
TI  - Genomic diversity within the Enterobacter cloacae complex.
AB  - BACKGROUND: Isolates of the Enterobacter cloacae complex have been increasingly
      isolated as nosocomial pathogens, but phenotypic identification of the E. cloacae
      complex is unreliable and irreproducible. Identification of species based on
      currently available genotyping tools is already superior to phenotypic
      identification, but the taxonomy of isolates belonging to this complex is
      cumbersome. METHODOLOGY/PRINCIPAL FINDINGS: This study shows that multilocus
      sequence analysis and comparative genomic hybridization based on a mixed genome
      array is a powerful method for studying species assignment within the E. cloacae
      complex. The E. cloacae complex is shown to be evolutionarily divided into two
      clades that are genetically distinct from each other. The younger first clade is
      genetically more homogenous, contains the Enterobacter hormaechei species and is
      the most frequently cultured Enterobacter species in hospitals. The second and
      older clade consists of several (sub)species that are genetically more
      heterogeneous. Genetic markers were identified that could discriminate between
      the two clades and cluster 1. CONCLUSIONS/SIGNIFICANCE: Based on genomic
      differences it is concluded that some previously defined (clonal and heterogenic)
      (sub)species of the E. cloacae complex have to be redefined because of
      disagreements with known or proposed nomenclature. However, further improved
      identification of the redefined species will be possible based on novel markers
      presented here.

PMID- 18716658
TI  - Clinical characteristics of 26 human cases of highly pathogenic avian influenza A
      (H5N1) virus infection in China.
AB  - BACKGROUND: While human cases of highly pathogenic avian influenza A (H5N1) virus
      infection continue to increase globally, available clinical data on H5N1 cases
      are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases
      identified through surveillance in China from October 2005 through April 2008.
      METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from hospital medical records
      of H5N1 cases and analyzed. The median age was 29 years (range 6-62) and 58% were
      female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset,
      and had lower respiratory findings of tachypnea and dyspnea at admission. All
      cases progressed rapidly to bilateral pneumonia. Clinical complications included
      acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated
      aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower
      median nadir platelet count (64.5 x 10(9) cells/L vs 93.0 x 10(9) cells/L, p =
      0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0
      U/L, p = 0.001), higher percentage of ARDS (94% [n = 16] vs 56% [n = 5], p =
      0.034) and more frequent cardiac failure (71% [n = 12] vs 11% [n = 1], p = 0.011)
      than nonfatal cases. A higher proportion of patients who received antiviral drugs
      survived compared to untreated (67% [8/12] vs 7% [1/14], p = 0.003).
      CONCLUSIONS/SIGNIFICANCE: The clinical course of Chinese H5N1 cases is
      characterized by fever and cough initially, with rapid progression to lower
      respiratory disease. Decreased platelet count, elevated LDH level, ARDS and
      cardiac failure were associated with fatal outcomes. Clinical management of H5N1
      cases should be standardized in China to include early antiviral treatment for
      suspected H5N1 cases.

PMID- 18716659
TI  - The early ANTP gene repertoire: insights from the placozoan genome.
AB  - The evolution of ANTP genes in the Metazoa has been the subject of conflicting
      hypotheses derived from full or partial gene sequences and genomic organization
      in higher animals. Whole genome sequences have recently filled in some crucial
      gaps for the basal metazoan phyla Cnidaria and Porifera. Here we analyze the
      complete genome of Trichoplax adhaerens, representing the basal metazoan phylum
      Placozoa, for its set of ANTP class genes. The Trichoplax genome encodes
      representatives of Hox/ParaHox-like, NKL, and extended Hox genes. This repertoire
      possibly mirrors the condition of a hypothetical cnidarian-bilaterian ancestor.
      The evolution of the cnidarian and bilaterian ANTP gene repertoires can be
      deduced by a limited number of cis-duplications of NKL and "extended Hox" genes
      and the presence of a single ancestral "ProtoHox" gene.

PMID- 18716660
TI  - Regenerating articular tissue by converging technologies.
AB  - Scaffolds for osteochondral tissue engineering should provide mechanical
      stability, while offering specific signals for chondral and bone regeneration
      with a completely interconnected porous network for cell migration, attachment,
      and proliferation. Composites of polymers and ceramics are often considered to
      satisfy these requirements. As such methods largely rely on interfacial bonding
      between the ceramic and polymer phase, they may often compromise the use of the
      interface as an instrument to direct cell fate. Alternatively, here, we have
      designed hybrid 3D scaffolds using a novel concept based on biomaterial assembly,
      thereby omitting the drawbacks of interfacial bonding. Rapid prototyped ceramic
      particles were integrated into the pores of polymeric 3D fiber-deposited (3DF)
      matrices and infused with demineralized bone matrix (DBM) to obtain constructs
      that display the mechanical robustness of ceramics and the flexibility of
      polymers, mimicking bone tissue properties. Ostechondral scaffolds were then
      fabricated by directly depositing a 3DF structure optimized for cartilage
      regeneration adjacent to the bone scaffold. Stem cell seeded scaffolds
      regenerated both cartilage and bone in vivo.

PMID- 18716661
TI  - The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural
      commitment.
AB  - Patterns of methylation at lysine 4 and 27 of histone H3 have been associated
      with states of gene activation and repression that are developmentally regulated
      and are thought to underlie the establishment of lineage specific gene expression
      programs. Recent studies have provided fundamental insight into the problem of
      lineage specification by comparing global changes in chromatin and transcription
      between ES and neural stem (NS) cells, points respectively of departure and
      arrival for neural commitment. With these maps of the differentiated state in
      place, a central task is now to unravel the chromatin dynamics that enables these
      differentiation transitions. In particular, the observation that lineage-specific
      genes repressed in ES cells by Polycomb-mediated H3-K27 trimethylation (H3
      K27me3) are demethylated and derepressed in differentiated cells posited the
      existence of a specific H3-K27 demethylase.In order to gain insight into the
      epigenetic transitions that enable lineage specification, we investigated the
      early stages of neural commitment using as model system the monolayer
      differentiation of mouse ES cells into neural stem (NS) cells. Starting from a
      comprehensive profiling of JmjC-domain genes, we report here that Jmjd3, recently
      identified as a H3-K27me3 specific demethylase, controls the expression of key
      regulators and markers of neurogenesis and is required for commitment to the
      neural lineage.Our results demonstrate the relevance of an enzymatic activity
      that antagonizes Polycomb regulation and highlight different modalities through
      which the dynamics of H3-K27me3 is related to transcriptional output. By showing
      that the H3-K27 demethylase Jmjd3 is required for commitment to the neural
      lineage and that it resolves the bivalent domain at the Nestin promoter, our work
      confirms the functional relevance of bivalent domain resolution that had been
      posited on the basis of the genome-wide correlation between their controlled
      resolution and differentiation. In addition, our data indicate that the
      regulation of H3-K27me3 is highly gene- and context- specific, suggesting that
      the interplay of methyltransferases and demethylases enables the fine-tuning more
      than the on/off alternation of methylation states.

PMID- 18716662
TI  - Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune
      disease.
AB  - Activation-induced cytidine deaminase (AID) expressed by germinal center B cells
      is a central regulator of somatic hypermutation (SHM) and class switch
      recombination (CSR). Humans with AID mutations develop not only the autosomal
      recessive form of hyper-IgM syndrome (HIGM2) associated with B cell hyperplasia,
      but also autoimmune disorders by unknown mechanisms. We report here that AID-/-
      mice spontaneously develop tertiary lymphoid organs (TLOs) in non-lymphoid
      tissues including the stomach at around 6 months of age. At a later stage, AID-/-
      mice develop a severe gastritis characterized by loss of gastric glands and
      epithelial hyperplasia. The disease development was not attenuated even under
      germ-free (GF) conditions. Gastric autoantigen -specific serum IgM was elevated
      in AID-/- mice, and the serum levels correlated with the gastritis pathological
      score. Adoptive transfer experiments suggest that autoimmune CD4+ T cells mediate
      gastritis development as terminal effector cells. These results suggest that
      abnormal B-cell expansion due to AID deficiency can drive B-cell autoimmunity,
      and in turn promote TLO formation, which ultimately leads to the propagation of
      organ-specific autoimmune effector CD4+ T cells. Thus, AID plays an important
      role in the containment of autoimmune diseases by negative regulation of
      autoreactive B cells.

PMID- 18716663
TI  - Pathology of Puumala hantavirus infection in macaques.
AB  - Hantaviruses are globally important human pathogens that cause hemorrhagic fever
      with renal syndrome and hantavirus pulmonary syndrome. Capillary leakage is
      central to hantaviral diseases, but how it develops, has remained unknown. It has
      been hypothesized that the pathogenesis of hantavirus infection would be a
      complex interplay between direct viral effects and immunopathological mechanisms.
      Both of these were studied in the so far best model of mild hemorrhagic fever
      with renal syndrome, i.e. cynomolgus macaques infected with wild-type Puumala
      hantavirus. Viral RNA detected by in situ hybridization and nucleocapsid protein
      detected by immunohistochemical staining were observed in kidney, spleen and
      liver tissues. Inflammatory cell infiltrations and tubular damage were found in
      the kidneys, and these infiltrations contained mainly CD8-type T-cells.
      Importantly, these results are consistent with those obtained from patients with
      hantaviral disease, thus showing that the macaque model of hantavirus infection
      mimics human infection also on the tissue level. Furthermore, both the markers of
      viral replication and the T-cells appeared to co-localize in the kidneys to the
      sites of tissue damage, suggesting that these two together might be responsible
      for the pathogenesis of hantavirus infection.

PMID- 18716665
TI  - JunB Inhibits ER Stress and Apoptosis in Pancreatic Beta Cells.
AB  - Cytokines contribute to pancreatic beta-cell apoptosis in type 1 diabetes (T1D)
      by modulation of beta-cell gene expression networks. The transcription factor
      Activator Protein-1 (AP-1) is a key regulator of inflammation and apoptosis. We
      presently evaluated the function of the AP-1 subunit JunB in cytokine-mediated
      beta-cell dysfunction and death. The cytokines IL-1beta+IFN-gamma induced an
      early and transitory upregulation of JunB by NF-kappaB activation. Knockdown of
      JunB by RNA interference increased cytokine-mediated expression of inducible
      nitric oxide synthase (iNOS) and endoplasmic reticulum (ER) stress markers,
      leading to increased apoptosis in an insulin-producing cell line (INS-1E) and in
      purified rat primary beta-cells. JunB knockdown beta-cells and junB(-/-)
      fibroblasts were also more sensitive to the chemical ER stressor cyclopiazonic
      acid (CPA). Conversely, adenoviral-mediated overexpression of JunB diminished
      iNOS and ER markers expression and protected beta-cells from cytokine-induced
      cell death. These findings demonstrate a novel and unexpected role for JunB as a
      regulator of defense mechanisms against cytokine- and ER stress-mediated
      apoptosis.

PMID- 18716664
TI  - Genome sequence of a Lancefield group C Streptococcus zooepidemicus strain
      causing epidemic nephritis: new information about an old disease.
AB  - Outbreaks of disease attributable to human error or natural causes can provide
      unique opportunities to gain new information about host-pathogen interactions and
      new leads for pathogenesis research. Poststreptococcal glomerulonephritis (PSGN),
      a sequela of infection with pathogenic streptococci, is a common cause of
      preventable kidney disease worldwide. Although PSGN usually occurs after
      infection with group A streptococci, organisms of Lancefield group C and G also
      can be responsible. Despite decades of study, the molecular pathogenesis of PSGN
      is poorly understood. As a first step toward gaining new information about PSGN
      pathogenesis, we sequenced the genome of Streptococcus equi subsp. zooepidemicus
      strain MGCS10565, a group C organism that caused a very large and unusually
      severe epidemic of nephritis in Brazil. The genome is a circular chromosome of
      2,024,171 bp. The genome shares extensive gene content, including many virulence
      factors, with genetically related group A streptococci, but unexpectedly lacks
      prophages. The genome contains many apparently foreign genes interspersed around
      the chromosome, consistent with the presence of a full array of genes required
      for natural competence. An inordinately large family of genes encodes secreted
      extracellular collagen-like proteins with multiple integrin-binding motifs. The
      absence of a gene related to speB rules out the long-held belief that
      streptococcal pyrogenic exotoxin B or antibodies reacting with it singularly
      cause PSGN. Many proteins previously implicated in GAS PSGN, such as
      streptokinase, are either highly divergent in strain MGCS10565 or are not more
      closely related between these species than to orthologs present in other
      streptococci that do not commonly cause PSGN. Our analysis provides a comparative
      genomics framework for renewed appraisal of molecular events underlying APSGN
      pathogenesis.

PMID- 18716666
TI  - Social Competence with Peers in Third Grade: Associations with Earlier Peer
      Experiences in Child Care.
AB  - The early developmental antecedents of individual differences in children's
      social functioning with peers in third grade were examined using longitudinal
      data from the large-scale NICHD Study of Early Child Care. In a sample of 1364
      children, with family and child factors controlled, the frequency of positive and
      negative peer interactions in child care between 24 and 54 months and the number
      of hours spent in child-care peer groups of different sizes (alone; dyad; small;
      medium; large), predicted third graders' peer competence at three levels of
      analysis: individual social skills, dyadic friendships, and peer group
      acceptance. Children who had more positive experiences with peers in child care
      had better social and communicative skills with peers in third grade, were more
      sociable and cooperative and less aggressive, had more close friends, and were
      more accepted and popular. Children with more frequent negative experiences with
      peers in child care were more aggressive in third grade, had lower social and
      communicative skills, and reported having fewer friends. When children spent more
      time in small-sized peer groups in child care (4 or fewer children at 24 months
      of age, up to 7 or fewer at 54 months), they were more sociable and cooperative
      in third grade, but their teachers rated them as more aggressive suggesting that
      such children may be more socially outgoing and active both positively and
      negatively. Like those who spent more time in small peer groups, children who
      spent more hours in medium-sized groups received higher ratings for peer
      aggression by their third grade teachers. Children who spent more time with one
      other child in child care or in small peer groups had fewer classroom friends in
      third grade as reported by the teacher but not according to maternal report or
      self report. There were no significant associations between the amount of time
      children spent in large child-care based peer groups and third grade peer social
      competence.

PMID- 18716667
TI  - Family Caregivers of Persons With Spinal Cord Injury: Predicting Caregivers at
      Risk for Probable Depression.
AB  - OBJECTIVE: To determine the percentage of family caregivers of persons with
      spinal cord injury (SCI) with probable depression and to test the hypothesis that
      dysfunctional problem-solving abilities would be significantly predictive of risk
      status after taking into account important demographic characteristics and
      caregiver health. DESIGN: Correlational and logistic regression analyses of data
      collected in a cross-sectional design. PARTICIPANTS: Eighteen men and 103 women
      caregivers (mean age of caregivers = 45.66 years, SD = 12.88) of individuals with
      SCI. MAIN OUTCOME MEASURE: The Inventory to Diagnose Depression. RESULTS:
      Nineteen caregivers (15.7%) met criteria on the Inventory to Diagnose Depression
      for a major depressive disorder. A dysfunctional problem-solving style was
      significantly predictive of caregiver depression, regardless of the severity of
      physical impairment of the care recipient or the physical health of the caregiver
      and caregiver demographic variables. CONCLUSIONS: The percentage of caregivers
      with probable depressive disorder may parallel that observed among persons with
      SCI, using a more conservative self-report measure designed to assess symptoms
      associated with a depressive syndrome. Family caregivers with a dysfunctional
      problem-solving style and assisting individuals with more severe injuries may
      have probable depression.

PMID- 18716668
TI  - Communal Behaviors and Psychological Adjustment of Family Caregivers and Persons
      With Spinal Cord Injury.
AB  - OBJECTIVE: Examined the influence of mutual communal behaviors on the adjustment
      reported by persons with spinal cord injury (SCI) and their family caregivers.
      Previous research has found that persons who have a history of mutually communal
      behaviors in relationships may react differently to relationship changes after an
      acquired physical disability than dyads with few communal behaviors. METHOD:
      Family caregivers and persons with SCI were administered measures of mutual
      communal behaviors, depression, and life satisfaction. Structural equation
      modeling was used to test the relations among caregivers' communal behaviors and
      care recipients' communal behaviors, depression, and life satisfaction. RESULTS:
      Caregiver and care recipient reports of communal behaviors were not significantly
      correlated. Significant paths indicated that care recipients' communal behavior
      scores were positively associated with their life satisfaction, and care
      recipients' depression was inversely associated with their life satisfaction.
      Caregivers' communal behavior scores were unrelated to their self-reported
      adjustment. CONCLUSIONS: Caregiver-care recipient dyads may differ in their
      perceptions of communal behaviors in their relationships. Although care recipient
      reports of communal behavior may be related to their life satisfaction, communal
      behaviors may not serve a similar function among caregivers of persons with SCI.

PMID- 18716669
TI  - Choline: Dietary Requirements and Role in Brain Development.
AB  - Choline is needed for the maintenance of the structural integrity and signaling
      functions of cell membranes, for neurotransmission, and for transport of lipids
      and as a source of methyl groups. Choline can be made de novo in the body, but
      some individuals must also obtain choline in the diet to prevent deficiency
      symptoms. A number of environmental and genetic factors influence dietary
      requirements for choline, and average intakes in the population vary widely.
      Therefore, certain individuals may be at greater risk of choline deficiency.
      Choline is critical during fetal development, particularly during the development
      of the brain, where it can influence neural tube closure and lifelong memory and
      learning functions.

PMID- 18716670
TI  - Family Caregivers of Women with Physical Disabilities.
AB  - Cross-sectional, correlational analyses of data from two separate studies were
      conducted to examine the correlates of adjustment among family caregivers of
      women with disabilities. Participants included 40 caregivers of women with spinal
      cord injuries in the first study and 53 caregivers of women with cerebral palsy,
      traumatic brain injury, and other neuromuscular disabilities in the second study.
      It was hypothesized that a negative problem-solving style would be associated
      with greater caregiver distress in both studies, and that caregiver adjustment
      would be associated with care recipient depression in the second study. As
      expected, results indicated that a higher negative orientation toward solving
      problems was associated with caregiver depression and lower well-being. However,
      in the second study, caregiver characteristics were not associated with care
      recipient depression. These data indicate that considerable variability exists in
      caregiver adjustment. Methodological limitations and the implications for
      research, service, and policy formation are! discussed.

PMID- 18716671
TI  - Signature-forecasting and early outbreak detection system.
AB  - Daily disease monitoring via a public health surveillance system provides
      valuable information on population risks. Efficient statistical tools for early
      detection of rapid changes in the disease incidence are a must for modern
      surveillance. The need for statistical tools for early detection of outbreaks
      that are not based on historical information is apparent. A system is discussed
      for monitoring cases of infections with a view to early detection of outbreaks
      and to forecasting the extent of detected outbreaks. We propose a set of adaptive
      algorithms for early outbreak detection that does not rely on extensive
      historical recording. We also include knowledge of infection disease epidemiology
      into forecasts. To demonstrate this system we use data from the largest water
      borne outbreak of cryptosporidiosis, which occurred in Milwaukee in 1993.
      Historical data are smoothed using a loess-type smoother. Upon receipt of a new
      datum, the smoothing is updated and estimates are made of the first two
      derivatives of the smooth curve, and these are used for near-term forecasting.
      Recent data and the near-term forecasts are used to compute a color-coded warning
      index, which quantify the level of concern. The algorithms for computing the
      warning index have been designed to balance Type I errors (false prediction of an
      epidemic) and Type II errors (failure to correctly predict an epidemic). If the
      warning index signals a sufficiently high probability of an epidemic, then a
      forecast of the possible size of the outbreak is made. This longer term forecast
      is made by fitting a 'signature' curve to the available data. The effectiveness
      of the forecast depends upon the extent to which the signature curve captures the
      shape of outbreaks of the infection under consideration.

PMID- 18716672
TI  - Modulation of serotonin transporter function during fetal development causes
      dilated heart cardiomyopathy and lifelong behavioral abnormalities.
AB  - BACKGROUND: Women are at great risk for mood and anxiety disorders during their
      childbearing years and may become pregnant while taking antidepressant drugs. In
      the treatment of depression and anxiety disorders, selective serotonin reuptake
      inhibitors (SSRIs) are the most frequently prescribed drugs, while it is largely
      unknown whether this medication affects the development of the central nervous
      system of the fetus. The possible effects are the product of placental transfer
      efficiency, time of administration and dose of the respective SSRI.
      METHODOLOGY/PRINCIPAL FINDINGS: In order to attain this information we have setup
      a study in which these parameters were measured and the consequences in terms of
      physiology and behavior are mapped. The placental transfer of fluoxetine and
      fluvoxamine, two commonly used SSRIs, was similar between mouse and human,
      indicating that the fetal exposure of these SSRIs in mice is comparable with the
      human situation. Fluvoxamine displayed a relatively low placental transfer, while
      fluoxetine showed a relatively high placental transfer. Using clinical doses of
      fluoxetine the mortality of the offspring increased dramatically, whereas the
      mortality was unaffected after fluvoxamine exposure. The majority of the
      fluoxetine-exposed offspring died postnatally of severe heart failure caused by
      dilated cardiomyopathy. Molecular analysis of fluoxetine-exposed offspring showed
      long-term alterations in serotonin transporter levels in the raphe nucleus.
      Furthermore, prenatal fluoxetine exposure resulted in depressive- and anxiety
      related behavior in adult mice. In contrast, fluvoxamine-exposed mice did not
      show alterations in behavior and serotonin transporter levels. Decreasing the
      dose of fluoxetine resulted in higher survival rates and less dramatic effects on
      the long-term behavior in the offspring. CONCLUSIONS: These results indicate that
      prenatal fluoxetine exposure affects fetal development, resulting in
      cardiomyopathy and a higher vulnerability to affective disorders in a dose
      dependent manner.

PMID- 18716673
TI  - Characterization of unique small RNA populations from rice grain.
AB  - Small RNAs (approximately 20 to 24 nucleotides) function as naturally occurring
      molecules critical in developmental pathways in plants and animals. Here we
      analyze small RNA populations from mature rice grain and seedlings by
      pyrosequencing. Using a clustering algorithm to locate regions producing small
      RNAs, we classified hotspots of small RNA generation within the genome. Hotspots
      here are defined as 1 kb regions within which small RNAs are significantly
      overproduced relative to the rest of the genome. Hotspots were identified to
      facilitate characterization of different categories of small RNA regulatory
      elements. Included in the hotspots, we found known members of 23 miRNA families
      representing 92 genes, one trans acting siRNA (ta-siRNA) gene, novel siRNA
      generating coding genes and phased siRNA generating genes. Interestingly, over
      20% of the small RNA population in grain came from a single foldback structure,
      which generated eight phased 21-nt siRNAs. This is reminiscent of a newly arising
      miRNA derived from duplication of progenitor genes. Our results provide data
      identifying distinct populations of small RNAs, including phased small RNAs, in
      mature grain to facilitate characterization of small regulatory RNA expression in
      monocot species.

PMID- 18716674
TI  - Classifying RNA-binding proteins based on electrostatic properties.
AB  - Protein structure can provide new insight into the biological function of a
      protein and can enable the design of better experiments to learn its biological
      roles. Moreover, deciphering the interactions of a protein with other molecules
      can contribute to the understanding of the protein's function within cellular
      processes. In this study, we apply a machine learning approach for classifying
      RNA-binding proteins based on their three-dimensional structures. The method is
      based on characterizing unique properties of electrostatic patches on the protein
      surface. Using an ensemble of general protein features and specific properties
      extracted from the electrostatic patches, we have trained a support vector
      machine (SVM) to distinguish RNA-binding proteins from other positively charged
      proteins that do not bind nucleic acids. Specifically, the method was applied on
      proteins possessing the RNA recognition motif (RRM) and successfully classified
      RNA-binding proteins from RRM domains involved in protein-protein interactions.
      Overall the method achieves 88% accuracy in classifying RNA-binding proteins, yet
      it cannot distinguish RNA from DNA binding proteins. Nevertheless, by applying a
      multiclass SVM approach we were able to classify the RNA-binding proteins based
      on their RNA targets, specifically, whether they bind a ribosomal RNA (rRNA), a
      transfer RNA (tRNA), or messenger RNA (mRNA). Finally, we present here an
      innovative approach that does not rely on sequence or structural homology and
      could be applied to identify novel RNA-binding proteins with unique folds and/or
      binding motifs.

PMID- 18716675
TI  - Quality of pharmaceutical industry press releases based on original research.
AB  - BACKGROUND: Press releases are a popular vehicle to disseminate health
      information to the lay media. While the quality of press releases issued by
      scientific conferences and medical journals has been questioned, no efforts to
      assess pharmaceutical industry press releases have been made. Therefore, we
      sought to systematically examine pharmaceutical company press releases about
      original research for measures of quality. METHODOLOGY/PRINCIPAL FINDINGS: Press
      releases issued by the ten top selling, international pharmaceutical companies in
      the year 2005 were selected for evaluation. A total of 1028 electronic press
      releases were issued and 235 were based on original research. More than half
      (59%) reported results presented at a scientific meeting. Twenty-one percent of
      releases were not explicit about the source of original data. While harms or
      adverse events were commonly cited (76%), study limitations were rarely noted
      (6%). Almost one-third (29%) of releases did not quantify study results. Studies
      presented in abstract form were subsequently published within at least 20 months
      in 53% of cases. CONCLUSIONS: Pharmaceutical company press releases frequently
      report basic study details. However, readers should be cautioned by the
      preliminary nature of the data and lack of identified limitations. Methods to
      improve the reporting and interpretation of drug company press releases are
      desirable to prevent misleading media coverage.

PMID- 18716676
TI  - Complex ecological dynamics and eradicability of the vector borne macroparasitic
      disease, lymphatic filariasis.
AB  - BACKGROUND: The current global efforts to control the morbidity and mortality
      caused by infectious diseases affecting developing countries--such as HIV/AIDS,
      polio, tuberculosis, malaria and the Neglected Tropical Diseases (NTDs)-have led
      to an increasing focus on the biological controllability or eradicability of
      disease transmission by management action. Here, we use an age-structured
      dynamical model of lymphatic filariasis transmission to show how a quantitative
      understanding of the dynamic processes underlying infection persistence and
      extinction is key to evaluating the eradicability of this macroparasitic disease.
      METHODOLOGY/PRINCIPAL FINDINGS: We investigated the persistence and extinction
      dynamics of lymphatic filariasis by undertaking a numerical equilibrium analysis
      of a deterministic model of parasite transmission, based on varying values of the
      initial L3 larval density in the system. The results highlighted the likely
      occurrence of complex dynamics in parasite transmission with three major outcomes
      for the eradicability of filariasis. First, both vector biting and worm
      breakpoint thresholds are shown to be complex dynamic entities with values
      dependent on the nature and magnitude of vector-and host specific density
      dependent processes and the degree of host infection aggregation prevailing in
      endemic communities. Second, these thresholds as well as the potential size of
      the attractor domains and hence system resilience are strongly dependent on
      peculiarities of infection dynamics in different vector species. Finally, the
      existence of multiple stable states indicates the presence of hysteresis
      nonlinearity in the filariasis system dynamics in which infection thresholds for
      infection invasion are lower but occur at higher biting rates than do the
      corresponding thresholds for parasite elimination. CONCLUSIONS/SIGNIFICANCE: The
      variable dynamic nature of thresholds and parasite system resilience reflecting
      both initial conditions and vector species-infection specificities, and the
      existence of hysteresis loop phenomenon, suggests that eradication of filariasis
      may require taking a more flexible and locally relevant approach to designing
      elimination programmes compared to the current command and control approach
      advocated by the global programme.

PMID- 18716677
TI  - Regulatory control and the costs and benefits of biochemical noise.
AB  - Experiments in recent years have vividly demonstrated that gene expression can be
      highly stochastic. How protein concentration fluctuations affect the growth rate
      of a population of cells is, however, a wide-open question. We present a
      mathematical model that makes it possible to quantify the effect of protein
      concentration fluctuations on the growth rate of a population of genetically
      identical cells. The model predicts that the population's growth rate depends on
      how the growth rate of a single cell varies with protein concentration, the
      variance of the protein concentration fluctuations, and the correlation time of
      these fluctuations. The model also predicts that when the average concentration
      of a protein is close to the value that maximizes the growth rate, fluctuations
      in its concentration always reduce the growth rate. However, when the average
      protein concentration deviates sufficiently from the optimal level, fluctuations
      can enhance the growth rate of the population, even when the growth rate of a
      cell depends linearly on the protein concentration. The model also shows that the
      ensemble or population average of a quantity, such as the average protein
      expression level or its variance, is in general not equal to its time average as
      obtained from tracing a single cell and its descendants. We apply our model to
      perform a cost-benefit analysis of gene regulatory control. Our analysis predicts
      that the optimal expression level of a gene regulatory protein is determined by
      the trade-off between the cost of synthesizing the regulatory protein and the
      benefit of minimizing the fluctuations in the expression of its target gene. We
      discuss possible experiments that could test our predictions.

PMID- 18716678
TI  - Coordinate regulation of G protein signaling via dynamic interactions of receptor
      and GAP.
AB  - Signal output from receptor-G-protein-effector modules is a dynamic function of
      the nucleotide exchange activity of the receptor, the GTPase-accelerating
      activity of GTPase-activating proteins (GAPs), and their interactions. GAPs may
      inhibit steady-state signaling but may also accelerate deactivation upon removal
      of stimulus without significantly inhibiting output when the receptor is active.
      Further, some effectors (e.g., phospholipase C-beta) are themselves GAPs, and it
      is unclear how such effectors can be stimulated by G proteins at the same time as
      they accelerate G protein deactivation. The multiple combinations of protein
      protein associations and interacting regulatory effects that allow such complex
      behaviors in this system do not permit the usual simplifying assumptions of
      traditional enzyme kinetics and are uniquely subject to systems-level analysis.
      We developed a kinetic model for G protein signaling that permits analysis of
      both interactive and independent G protein binding and regulation by receptor and
      GAP. We evaluated parameters of the model (all forward and reverse rate
      constants) by global least-squares fitting to a diverse set of steady-state
      GTPase measurements in an m1 muscarinic receptor-G(q)-phospholipase C-beta1
      module in which GTPase activities were varied by approximately 10(4)-fold. We
      provide multiple tests to validate the fitted parameter set, which is consistent
      with results from the few previous pre-steady-state kinetic measurements. Results
      indicate that (1) GAP potentiates the GDP/GTP exchange activity of the receptor,
      an activity never before reported; (2) exchange activity of the receptor is
      biased toward replacement of GDP by GTP; (3) receptor and GAP bind G protein with
      negative cooperativity when G protein is bound to either GTP or GDP, promoting
      rapid GAP binding and dissociation; (4) GAP indirectly stabilizes the continuous
      binding of receptor to G protein during steady-state GTPase hydrolysis, thus
      further enhancing receptor activity; and (5) receptor accelerates GDP/GTP
      exchange primarily by opening an otherwise closed nucleotide binding site on the
      G protein but has minimal effect on affinity (K(assoc) = k(assoc)/k(dissoc)) of G
      protein for nucleotide. Model-based simulation explains how GAP activity can
      accelerate deactivation >10-fold upon removal of agonist but still allow high
      signal output while the receptor is active. Analysis of GTPase flux through
      distinct reaction pathways and consequent accumulation of specific GTPase cycle
      intermediates indicate that, in the presence of a GAP, the receptor remains bound
      to G protein throughout the GTPase cycle and that GAP binds primarily during the
      GTP-bound phase. The analysis explains these behaviors and relates them to the
      specific regulatory phenomena described above. The work also demonstrates the
      applicability of appropriately data-constrained system-level analysis to
      signaling networks of this scale.

PMID- 18716679
TI  - Oil and gas projects in the Western Amazon: threats to wilderness, biodiversity,
      and indigenous peoples.
AB  - BACKGROUND: The western Amazon is the most biologically rich part of the Amazon
      basin and is home to a great diversity of indigenous ethnic groups, including
      some of the world's last uncontacted peoples living in voluntary isolation.
      Unlike the eastern Brazilian Amazon, it is still a largely intact ecosystem.
      Underlying this landscape are large reserves of oil and gas, many yet untapped.
      The growing global demand is leading to unprecedented exploration and development
      in the region. METHODOLOGY/PRINCIPAL FINDINGS: We synthesized information from
      government sources to quantify the status of oil development in the western
      Amazon. National governments delimit specific geographic areas or "blocks" that
      are zoned for hydrocarbon activities, which they may lease to state and
      multinational energy companies for exploration and production. About 180 oil and
      gas blocks now cover approximately 688,000 km(2) of the western Amazon. These
      blocks overlap the most species-rich part of the Amazon. We also found that many
      of the blocks overlap indigenous territories, both titled lands and areas
      utilized by peoples in voluntary isolation. In Ecuador and Peru, oil and gas
      blocks now cover more than two-thirds of the Amazon. In Bolivia and western
      Brazil, major exploration activities are set to increase rapidly.
      CONCLUSIONS/SIGNIFICANCE: Without improved policies, the increasing scope and
      magnitude of planned extraction means that environmental and social impacts are
      likely to intensify. We review the most pressing oil- and gas-related
      conservation policy issues confronting the region. These include the need for
      regional Strategic Environmental Impact Assessments and the adoption of roadless
      extraction techniques. We also consider the conflicts where the blocks overlap
      indigenous peoples' territories.

PMID- 18716680
TI  - Gene expression and functional studies of the optic nerve head astrocyte
      transcriptome from normal African Americans and Caucasian Americans donors.
AB  - PURPOSE: To determine whether optic nerve head (ONH) astrocytes, a key cellular
      component of glaucomatous neuropathy, exhibit differential gene expression in
      primary cultures of astrocytes from normal African American (AA) donors compared
      to astrocytes from normal Caucasian American (CA) donors. METHODS: We used
      oligonucleotide Affymetrix microarray (HG U133A & HG U133A 2.0 chips) to compare
      gene expression levels in cultured ONH astrocytes from twelve CA and twelve AA
      normal age matched donor eyes. Chips were normalized with Robust Microarray
      Analysis (RMA) in R using Bioconductor. Significant differential gene expression
      levels were detected using mixed effects modeling and Statistical Analysis of
      Microarray (SAM). Functional analysis and Gene Ontology were used to classify
      differentially expressed genes. Differential gene expression was validated by
      quantitative real time RT-PCR. Protein levels were detected by Western blots and
      ELISA. Cell adhesion and migration assays tested physiological responses.
      Glutathione (GSH) assay detected levels of intracellular GSH. RESULTS: Multiple
      analyses selected 87 genes differentially expressed between normal AA and CA
      (P<0.01). The most relevant genes expressed in AA were categorized by function,
      including: signal transduction, response to stress, ECM genes, migration and cell
      adhesion. CONCLUSIONS: These data show that normal astrocytes from AA and CA
      normal donors display distinct expression profiles that impact astrocyte
      functions in the ONH. Our data suggests that differences in gene expression in
      ONH astrocytes may be specific to the development and/or progression of glaucoma
      in AA.

PMID- 18716681
TI  - Circadian genes are expressed during early development in Xenopus laevis.
AB  - BACKGROUND: Circadian oscillators are endogenous time-keeping mechanisms that
      drive twenty four hour rhythmic changes in gene expression, metabolism, hormone
      levels, and physical activity. We have examined the developmental expression of
      genes known to regulate circadian rhythms in order to better understand the
      ontogeny of the circadian clock in a vertebrate. METHODOLOGY/PRINCIPAL FINDINGS:
      In this study, genes known to function together in part of the core circadian
      oscillator mechanism (xPeriod1, xPeriod2, and xBmal1) as well as a rhythmic,
      clock-controlled gene (xNocturnin) were analyzed using in situ hybridization in
      embryos from neurula to late tailbud stages. Each transcript was present in the
      developing nervous system in the brain, eye, olfactory pit, otic vesicle and at
      lower levels in the spinal cord. These genes were also expressed in the
      developing somites and heart, but at different developmental times in peripheral
      tissues (pronephros, cement gland, and posterior mesoderm). No difference was
      observed in transcript levels or localization when similarly staged embryos
      maintained in cyclic light were compared at two times of day (dawn and dusk) by
      in situ hybridization. Quantitation of xBmal1 expression in embryonic eyes was
      also performed using qRT-PCR. Eyes were isolated at dawn, midday, dusk, and
      midnight (cylic light). No difference in expression level between time-points was
      found in stage 31 eyes (p = 0.176) but stage 40 eyes showed significantly
      increased levels of xBmal1 expression at midnight (RQ = 1.98+/-0.094) when
      compared to dawn (RQ = 1+/-0.133; p = 0.0004). CONCLUSIONS/SIGNIFICANCE: We
      hypothesize that when circadian genes are not co-expressed in the same tissue
      during development that it may indicate pleiotropic functions of these genes that
      are separate from the timing of circadian rhythm. Our results show that all
      circadian genes analyzed thus far are present during early brain and eye
      development, but rhythmic gene expression in the eye is not observed until after
      stage 31 of development.

PMID- 18716683
TI  - Burkholderia pseudomallei infection in a cystic fibrosis patient from the
      Caribbean: a case report.
AB  - Burkholderia pseudomallei is a pathogen identified with increasing frequency in
      the respiratory tracts of cystic fibrosis (CF) patients from endemic areas such
      as Southeast Asia and northern Australia. The following report describes the
      first known reported case in a CF patient from the Caribbean attending a North
      American CF clinic.

PMID- 18716684
TI  - Treatment of a tuberculous empyema with simultaneous oral and intrapleural
      antituberculosis drugs.
AB  - A 71-year-old man was diagnosed with an uncomplicated tuberculous (TB) empyema.
      Differential penetration of anti-TB drugs, believed to explain the phenomenon of
      acquired drug resistance in TB empyema, was confirmed by measurement of serum and
      pleural fluid anti-TB drug concentrations. Simultaneous oral and intrapleural
      anti-TB drugs were administered and a cure was achieved. The present case is
      discussed in the context of the literature on acquired drug resistance in TB
      empyema. It is argued that high-end doses of oral drugs or combined oral plus
      intrapleural drugs, along with tube thoracostomy or intermittent thoracentesis,
      will cure uncomplicated TB empyema without threatening to induce drug resistance
      or having to resort to surgery.

PMID- 18716682
TI  - A fluorescent glycolipid-binding peptide probe traces cholesterol dependent
      microdomain-derived trafficking pathways.
AB  - BACKGROUND: The uptake and intracellular trafficking of sphingolipids, which self
      associate into plasma membrane microdomains, is associated with many pathological
      conditions, including viral and toxin infection, lipid storage disease, and
      neurodegenerative disease. However, the means available to label the trafficking
      pathways of sphingolipids in live cells are extremely limited. In order to
      address this problem, we have developed an exogenous, non-toxic probe consisting
      of a 25-amino acid sphingolipid binding domain, the SBD, derived from the amyloid
      peptide Abeta, and conjugated by a neutral linker with an organic fluorophore.
      The current work presents the characterization of the sphingolipid binding and
      live cell trafficking of this novel probe, the SBD peptide. SBD was the name
      given to a motif originally recognized by Fantini et al in a number of glycolipid
      associated proteins, and was proposed to interact with sphingolipids in membrane
      microdomains. METHODOLOGY/PRINCIPAL FINDINGS: In accordance with Fantini's model,
      optimal SBD binding to membranes depends on the presence of sphingolipids and
      cholesterol. In synthetic membrane binding assays, SBD interacts preferentially
      with raft-like lipid mixtures containing sphingomyelin, cholesterol, and complex
      gangliosides in a pH-dependent manner, but is less glycolipid-specific than
      Cholera toxin B (CtxB). Using quantitative time-course colocalization in live
      cells, we show that the uptake and intracellular trafficking route of SBD is
      unlike that of either the non-raft marker Transferrin or the raft markers CtxB
      and Flotillin2-GFP. However, SBD traverses an endolysosomal route that partially
      intersects with raft-associated pathways, with a major portion being diverted at
      a late time point to rab11-positive recycling endosomes. Trafficking of SBD to
      acidified compartments is strongly disrupted by cholesterol perturbations,
      consistent with the regulation of sphingolipid trafficking by cholesterol.
      CONCLUSIONS/SIGNIFICANCE: The current work presents the characterization and
      trafficking behavior of a novel sphingolipid-binding fluorescent probe, the SBD
      peptide. We show that SBD binding to membranes is dependent on the presence of
      cholesterol, sphingomyelin, and complex glycolipids. In addition, SBD targeting
      through the endolysosomal pathway in neurons is highly sensitive to cholesterol
      perturbations, making it a potentially useful tool for the analysis of
      sphingolipid trafficking in disease models that involve changes in cholesterol
      metabolism and storage.

PMID- 18716685
TI  - Delayed tuberculosis treatment in urban and suburban Ontario.
AB  - BACKGROUND: Delay in the treatment of patients with tuberculosis (TB) increases
      the risk of poor clinical outcomes--including death and transmission of disease-
      and may be reducible. OBJECTIVE: To estimate delays in TB treatment in a
      Canadian, multicultural population and to examine factors associated with longer
      time to treatment. METHODS: Adult cases of active TB from January 1998 to
      December 2001 from the Ontario Reportable Disease Information System were
      included. Time to treatment was defined as the number of days between symptom
      onset and treatment. RESULTS: Data from 1753 TB patients (76% of eligible
      patients) were analyzed. Median time to treatment was 62 days (interquartile
      range 31 to 114 days). Time periods longer than the median time to treatment were
      independently associated with middle-aged patients (OR 1.54, 95% CI 1.21 to
      1.98), foreign-born patients who had lived in Canada for more than 10 years (OR
      1.47, 95% CI 1.02 to 2.12), patients with nonpulmonary disease (OR 1.57, 95% CI
      1.28 to 1.92) and patients managed within certain health districts. CONCLUSION: A
      time to TB treatment of two months or more is common in Ontario, and associated
      with several factors. Future studies are needed to build on these findings to
      decrease delay and improve individual and public health outcomes.

PMID- 18716686
TI  - Toward optimal end-of-life care for patients with advanced chronic obstructive
      pulmonary disease: insights from a multicentre study.
AB  - BACKGROUND: Understanding patients' needs and perspectives is fundamental to
      improving end-of-life (EOL) care. However, little is known of what quality care
      means to patients who have advanced lung disease. OBJECTIVES: To describe ratings
      of importance and satisfaction with elements of EOL care, informational needs,
      decision-making preferences, obstacles to a preferred location of death, clinical
      outcomes, and health care use before and during an index hospital admission for
      patients who have advanced chronic obstructive pulmonary disease (COPD). METHODS:
      A questionnaire with regard to quality EOL care was administered to patients
      older than 55 years of age who had advanced medical disease in five Canadian
      teaching hospitals. RESULTS: For 118 hospitalized patients who had advanced COPD,
      the following items were rated as extremely important for EOL care: not being
      kept alive on life support when there is little hope for meaningful recovery
      (54.9% of respondents), symptom relief (46.6%), provision of care and health
      services after discharge (40.0%), trust and confidence in physicians (39.7%), and
      not being a burden on caregivers (39.6%). Compared with patients who had
      metastatic cancer, patients with COPD had lower (P<0.05) satisfaction with care,
      interest in information about prognosis, cardiopulmonary resuscitation or
      mechanical ventilation, and referral rates to palliative care, whereas use of
      acute care services was higher (P<0.05) for patients who had advanced COPD.
      CONCLUSION: Canadian patients who have advanced COPD identify several priorities
      for improving care. Avoidance of prolonged or unwanted life support requires more
      effective communication, decision making and goal setting. Patients also deserve
      better symptom control and postdischarge strategies to minimize perceived burdens
      on caregivers, emergency room visits and hospital admissions.

PMID- 18716687
TI  - Residual hemothorax after chest tube placement correlates with increased risk of
      empyema following traumatic injury.
AB  - BACKGROUND: Empyema complicates tube thoracostomy following trauma in up to 10%
      of cases. Studies of potential risk factors of empyema have included use of
      antibiotics, site of injury and technique of chest tube placement. Residual fluid
      has also been cited as a risk factor for empyema, although the imaging technique
      to identify this varies. OBJECTIVE: To determine whether residual hemothorax
      detected by chest x-ray (CXR) after one or more initial chest tubes predicts an
      increased risk of empyema. METHODS: A study of patients admitted to two level I
      trauma centres between January 7, 2004, and December 31, 2004, was conducted. All
      patients who received a chest tube in the emergency department, did not undergo
      thoracotomy within 24 h, and survived more than two days were followed. Empyema
      was defined as a pleural effusion with positive cultures, and a ratio of pleural
      fluid lactate dehydrogenase to serum lactate dehydrogenase greater than 0.6 in
      the setting of elevated leukocyte count and fever. Factors analyzed included the
      presence of retained hemothorax on CXR after the most recent tube placement in
      the emergency room, age, mechanism of injury and injury severity score. RESULTS:
      A total of 102 patients met the criteria. Nine patients (9%) developed empyema:
      seven of 21 patients (33%) with residual hemothorax developed empyema versus two
      of 81 patients (2%) without residual hemothorax developed empyema (P=0.001).
      Injury severity score was significantly higher in those who developed empyema
      (31.4+/-26) versus those who did not (22.6+/-13; P=0.03). CONCLUSIONS: The
      presence of residual hemothorax detected by CXR after tube thoracostomy should
      prompt further efforts, including thoracoscopy, to drain it. With increasing
      injury severity, there may be increased benefit in terms of reducing empyema with
      this approach.

PMID- 18716688
TI  - A pilot study to compare tobramycin 80 mg injectable preparation with 300 mg
      solution for inhalation in cystic fibrosis patients.
AB  - BACKGROUND: Inhaled tobramycin has been shown to improve lung function in cystic
      fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. However,
      to date no comparative data are available for different dose regimens used in
      clinical practice. OBJECTIVES: To compare the clinical efficacy of the two most
      commonly used treatment regimens of inhaled tobramycin in patients with CF.
      METHODS: In an open crossover study of CF patients, subjects were randomly
      allocated to receive either 80 mg tobramycin twice-daily continuous treatment or
      300 mg tobramycin twice daily in cycles of 28 days on and 28 days off treatment.
      After three months, patients were switched to the alternative treatment regimen.
      RESULTS: A total of 32 patients with a mean (+/- SD) age of 18.5+/-8.6 years were
      included in the study. Compared with the treatment period using colistin, forced
      expiratory volume in 1 s decreased by -2.1+/-13.8% in the 80 mg tobramycin group
      and increased by +2.3+/-13.0% in the 300 mg group. Similar changes were observed
      in forced vital capacity (-2.5+/-12.9% in the 80 mg tobramycin group versus
      +2.5+/-9.6% in the 300 mg tobramycin group). Variability in responses was large
      but the differences were not statistically significant. Personal preference
      indicated that the majority of patients preferred the high-dose cycle compared
      with the lower dose continuous inhalation, but this was not linked to objective
      data on efficacy. CONCLUSIONS: The present trial fails to provide convincing
      evidence for superiority in efficacy of either of the two treatment regimens of
      inhaled tobramycin in CF patients.

PMID- 18716690
TI  - Adjuvant chemotherapy in resected lung cancer: two-year experience in a
      university hospital.
AB  - BACKGROUND: Randomized trials have confirmed the benefits of adjuvant
      chemotherapy in improving survival in resected early-stage non-small-cell lung
      cancer (NSCLC). The extent to which these results have translated into clinical
      practice is unknown. OBJECTIVE: To examine the referral pattern of patients with
      resected lung cancer to adjuvant chemotherapy, and to compare compliance and
      toxicities with current literature. METHODS: A retrospective analysis of all
      patients who underwent a surgical resection for lung cancer at Laval Hospital
      (Quebec City, Quebec) from March 2004 to January 2006 was conducted. RESULTS: A
      total of 258 patients underwent surgery. Seven patients were excluded because of
      early postoperative death, and two patients were excluded because of incomplete
      data. Data from 249 patients were analyzed (94% NSCLC). Fifty per cent were
      referred to medical oncology for consideration of adjuvant chemotherapy,
      including 37 of 61 patients with stage II NSCLC. One hundred patients received
      chemotherapy. No significant difference in age, sex, comorbidities and surgical
      procedures was observed between those who received chemotherapy and those who did
      not. Chemotherapy was initiated 47 days (median) after the surgery and consisted
      mainly of cisplatin-vinorelbine (38%), cisplatin-etoposide (22%) and carboplatin
      paclitaxel (20%). Sixty-six per cent of the patients completed all four cycles.
      Grade 3 or 4 toxicities consisted mainly of fatigue (23%) and cytopenia (40%). No
      death was registered; 15% had to be hospitalized because of adverse effects.
      CONCLUSION: Although adjuvant chemotherapy is gaining acceptance in clinical
      practice, more patients should be referred to medical oncology following surgical
      resection. Compliance and toxicity are similar to or better than those described
      in published randomized trials.

PMID- 18716689
TI  - Second-hand smoke exposure in Canada: prevalence, risk factors, and association
      with respiratory and cardiovascular diseases.
AB  - OBJECTIVES: The aims of the present study were to estimate the prevalence of
      second-hand smoke exposure in Canada, to identify sociodemographic risk factors
      for second-hand smoke exposure, and to examine the relationship between second
      hand smoke exposure and respiratory and cardiovascular diseases. METHODS: Data
      from the 2000/2001 Statistics Canada Canadian Community Health Survey (n=130,880,
      aged 12 years or older) were analyzed. Second-hand smoke exposure was based on
      self-report within the past month. The presence of chronic health conditions was
      also based on self-report. Because ex-smokers would be expected a priori to have
      poorer health than never-smokers, the analysis was stratified by previous smoking
      status. RESULTS: Approximately 25% of never-smokers and 30% of ex-smokers self
      reported recent second-hand smoke exposure. The following factors were identified
      as risk factors for second-hand smoke exposure: men; residences in Quebec,
      Atlantic Canada and the Territories; younger ages; nonimmigrant status; low
      education and income levels; social assistance receipt; and households without
      children younger than 12 years of age. After controlling for potential
      confounders, both never- and ex-smokers exposed to second-hand smoke had
      significantly higher odds of self-reporting asthma (20% to 30%) and chronic
      bronchitis (50%) than those not exposed to second-hand smoke. Among ex-smokers,
      those exposed to second-hand smoke also had significantly higher odds of self
      reporting hypertension (20%) than those not exposed to second-hand smoke. No
      associations were observed between second-hand smoke exposure and emphysema or
      heart disease. CONCLUSIONS: Self-reported recent second-hand smoke exposure in
      Canada in 2000/2001 was high, and was associated with asthma, chronic bronchitis
      and hypertension in never- and ex-smokers. Potential causal associations and
      public health implications warrant additional research.

PMID- 18716692
TI  - Quality measures--getting at what really matters.

PMID- 18716691
TI  - Influence of current or former smoking on asthma management and control.
AB  - BACKGROUND: In patients with asthma, smoking has been associated with accelerated
      decline in pulmonary function, poor disease control and reduced responsiveness to
      corticosteroids. OBJECTIVE: To assess the influence of current and former smoking
      on self-reported asthma control and health care use in a large population of
      asthma patients. METHODS: The present analysis was conducted following a
      telephone survey of adult Canadians aged 18 to 54 years who had physician
      diagnosed asthma and a smoking history of less than 20 pack-years. RESULTS: Of
      893 patients, 268 were former smokers and 108 were current smokers. Daytime and
      nighttime symptoms, absenteeism from work or school, emergency care use for
      asthma in the past year, and use of a short-acting bronchodilator without
      controller medication were reported more frequently by current smokers than
      nonsmokers and former smokers. Former smokers were not significantly different
      from nonsmokers with respect to most asthma outcomes. CONCLUSIONS: Current
      smokers with asthma show evidence of poorer asthma control and greater acute care
      needs than lifelong nonsmokers or former smokers. These observations stress the
      importance of smoking cessation to help achieve asthma control.

PMID- 18716693
TI  - Coracoclavicular stabilization using a suture anchor technique.
AB  - Multiple fixation options exist for coracoclavicular stabilization, but many are
      technically demanding and require hardware removal. In the study reported here,
      we reviewed a specific fixation technique that includes suture anchors moored in
      the base of the coracoid process. We retrospectively reviewed 24 consecutive
      cases of patients who underwent coracoclavicular stabilization with a suture
      anchor for a type III or type V acromioclavicular (AC) joint separation or a
      group II, type II or type V distal clavicle fracture. Eighteen of the 22 patients
      had full strength and painless range of motion (ROM) in the affected extremity by
      3 months and at final follow-up (minimum, 24 months; mean, 39 months). Two
      patients were lost to follow-up. Four patients had early complications likely
      secondary to documented noncompliance. Two of these 4 patients underwent
      reoperation with a similar procedure and remained asymptomatic at a minimum
      follow-up of 15 months. One patient underwent osteophyte and knot excision 7
      months after surgery and remained asymptomatic at 30 months. Our results suggest
      that coracoclavicular stabilization using a suture anchor technique is a safe and
      reliable method of treating acromioclavicular joint separations and certain
      distal clavicle fractures in the compliant patient.

PMID- 18716694
TI  - Anterior cruciate ligament reconstruction with Achilles tendon allografts in
      revisions and in patients older than 30.
AB  - We evaluated the results of anterior cruciate ligament (ACL) reconstruction using
      an Achilles tendon allograft in revisions and in patients older than 30. Results
      from 23 consecutive patients (mean age, 43 years) who underwent ACL
      reconstruction with fresh-frozen, irradiated (22/23) Achilles allografts were
      retrospectively reviewed. Seven cases were revisions. Patients were evaluated
      with physical examination, questionnaires, and x-rays. Twenty of the 23 patients
      were evaluated a mean of 28 months after surgery. There were 5 failures (21%); 3
      acute failures were not evaluated at follow-up. One patient had an infection that
      required graft removal, 2 patients had mechanical failure of the grafts, and 2
      had displacements of more than 5.5 mm as measured with a KT-1000 arthrometer. The
      18 clinically successful cases had full motion, no thigh atrophy, and no
      effusion. Pivot shift scores were 55% A and 45% B on the International Knee
      Documentation Committee (IKDC) scale. Lachman scores were 40% A, 55% B, and 5% C
      on the IKDC scale. The KT-1000 difference was a mean of 2.9 mm at final follow
      up. However, knees loosened a mean of 4.5 mm from the immediate postoperative
      measurements (P<.0001). Mean Lysholm and Tegner scores were 86.8 and 5.2,
      respectively. Tibial tunnel diameter increased by 3.1 mm on anteroposterior x
      rays and 3.0 mm on lateral x-rays. Five patients developed mild medial
      compartment arthritis. Four of the 5 grafts with failures were from donors older
      than 40. Postoperative complications included deep vein thrombosis and
      inflammatory effusion (white blood cell count, 15,000). Twenty-one percent of ACL
      reconstructions with Achilles tendon allografts failed. Grafts deemed successful
      still had significant loosening at final follow-up. Allografts from donors older
      than 40 may have played a role in these failures. From the data in this study, it
      appears that surgeons should scrutinize the source of the allograft tissue and
      the age of the donor.

PMID- 18716695
TI  - Incidence and variance of knee injuries in elite college football players.
AB  - Knee injuries are among the most common musculoskeletal injuries in US football
      players. The literature includes little information about the role of player
      position and risk for knee injury. We hypothesized that the incidence of knee
      injury in elite collegiate US football players is high and that type of injury
      varies by player position. We evaluated 332 elite collegiate US football players
      at the 2005 National Football League Combine. All players underwent radiographic
      examinations, including plain x-rays and/or magnetic resonance imaging when
      necessary. All knee pathologic conditions and surgical procedures were recorded.
      Data were analyzed by player position to detect any trends. Fifty-four percent
      (179) of the 332 players had a history of knee injury; knee injuries totaled 233
      (1.3/player injured). Eighty-six players (25.9%) had a total of 114 surgeries.
      The most common injuries were medial collateral ligament injury (n = 79),
      meniscal injury (n = 51), and anterior cruciate ligament (ACL) injury (n = 40).
      The most common surgeries were arthroscopic meniscectomy (n = 39), ACL
      reconstruction (n = 35), and arthroscopic meniscal repair (n = 13). A history of
      knee injury was most common in defensive linemen (68% of players), tight ends
      (57%), and offensive linemen (57%). Knee surgery was more commonly performed on
      running backs (36%) and linebackers (34%). There were no significant associations
      between type or frequency of specific injuries with regard to player position.
      Knee injuries are common injuries in elite collegiate football players, and one
      fourth of these players undergo surgical procedures. However, there were no
      statistically significant differences in type or frequency of injuries by player
      position.

PMID- 18716696
TI  - Bilateral femoral insufficiency fractures presenting as knee pain in a patient
      with hypophosphatemic vitamin D-resistant rickets.

PMID- 18716697
TI  - Avascular necrosis of the femoral head following intramedullary nailing of the
      femur in a skeletally mature young adult: a case report.
AB  - Avascular necrosis (AVN) of the femoral head is a well-documented complication of
      intramedullary nailing (IMN) of femoral shaft fractures in adolescents and
      children (age range, 10 years to 13 years 10 months). In adults, AVN after IMN
      has been reported in association with femoral neck fractures, intra-articular hip
      injuries, steroid use, and various other medical conditions. With those factors
      set aside, the literature includes only 1 case of AVN after IMN in an adult. Now
      we report the case of a previously healthy, skeletally mature young adult male
      who, at age 16 years 0 month, was treated with IMN after a traumatic femoral
      shaft fracture and subsequently developed AVN of the femoral head.

PMID- 18716698
TI  - A new technique for establishing and maintaining an anteromedial knee portal.
AB  - Precise placement of the anteromedial portal is critical to the safety and
      efficacy of knee arthroscopy. Our described technique establishes and maintains a
      properly placed portal with minimal capsular violation using a needle arthrotomy
      and the outer shaver barrel as a cannula. This technique has the dual benefit of
      optimizing instrument access to the knee without large portal arthrotomies and
      reducing postoperative pain and swelling by minimizing fluid extravasation.

PMID- 18716699
TI  - Unusual doesn't mean unusable: why information about uncommon injuries or
      conditions is important.

PMID- 18716700
TI  - Volar forearm compartment syndrome following flexor digitorum profundus muscle
      rupture in a 3-year-old girl.

PMID- 18716701
TI  - Knee dislocation in a 9-year-old boy.

PMID- 18716702
TI  - Development of bilateral lower extremity Marjolin ulcers after childhood burns.

PMID- 18716703
TI  - Open tibiotalar dislocation without associated fracture in a 7-year-old girl.

PMID- 18716704
TI  - Symptom resolution and sexual function after anterior vaginal wall repair with or
      without polypropylene mesh.
AB  - To evaluate whether symptom resolution and sexual function is better after
      reinforcement with polypropylene mesh than with traditional anterior repair.
      Ninety-seven patients were randomized to anterior colporrhaphy and 105 to an
      operation with mesh. Participants were evaluated up to 24 months by physical
      examination, standard questions, and questionnaire. The overall symptom rate did
      not differ between the groups, but a sensation of vaginal bulge was reported less
      frequently in the mesh group, the figures being 17 versus 5 (p = 0.003). The
      recurrence rate for the no-mesh group was 41% and for the mesh group 11% (p <
      0.001). The dyspareunia score was statistically significantly lower in the mesh
      group (p = 0.015). The mesh exposure rate was 8%. Sensation of vaginal bulge was
      relieved more efficiently by the mesh technique without causing dyspareunia.

PMID- 18716705
TI  - Transurethral mesh resection after urethral erosion of tension-free vaginal tape:
      report of three cases and review of literature.
AB  - A rare complication after tension-free vaginal tape (TVT; including TVT-O)
      procedure is erosion of the tape through the urethral wall. In the literature,
      different methods to remove this intra-urethral tape are described. Most authors
      used the transvaginal approach with urethrotomy. In the cases described in this
      article, the transurethral approach is applied and proposed as the optimal
      method, being minimally invasive and less damaging to the urethral wall A
      transurethral catheter can be removed shortly after surgery to enable optimal
      tissue healing of the urethral mucosa.

PMID- 18716706
TI  - The longitudinal course of cardiomyopathy in Friedreich's ataxia during
      childhood.
AB  - BACKGROUND: Clinical heart disease was recognized in the first descriptions of
      Friedreich's ataxia (FA). Cardiac manifestations reported for this progressive
      neurologic disease include hypertrophic cardiomyopathy, dilated cardiomyopathy,
      and electrophysiologic disturbances. Longitudinal data for childhood cases are
      limited. This study aimed to define the longitudinal course of the cardiac
      abnormalities with FA diagnosed during childhood and to correlate the presence of
      cardiomyopathy with clinical and genetic factors. METHODS: A retrospective chart
      review was conducted, with prospective, blinded interpretation of echocardiograms
      and electrocardiograms. All the patients with a diagnosis of FA referred to the
      cardiology department of a single institution from 1974 to 2004 were included in
      the study. RESULTS: This study investigated a total of 113 echocardiograms for 28
      patients. Overall, the group had left ventricular hypertrophy and normal systolic
      function, with a median mass z-score of 2.48 (range, -3.8 to 35.6) and a median
      ejection fraction (EF) of 61% (range, 23-81%). Of the 28 patients, 23 (82%) had
      two or more echocardiograms. The median follow-up time to the most recent
      echocardiogram was 5.1 years (range, 0.4-16.5 years). Many in this longitudinal
      follow-up cohort (57%) showed hypertrophic cardiomyopathy on at least one
      echocardiogram, with the last follow-up assessment showing systolic dysfunction
      for 38% of these patients. There was a slow nonlinear decline in systolic
      function over time, with the mean EF decreasing more rapidly as age increased (p
      = 0.02) and maintenance of EF in the normal range until the age of 22 years. Of
      the 12 patients with systolic dysfunction and follow-up echocardiograms, 10
      showed improvement to the normal EF range on at least one echocardiogram, and 5
      remained normal through the last study. None of the trends in cardiac function
      and morphology correlated with frataxin GAA repeat length (the primary genetic
      defect in FA) or ambulatory status. One patient required an implantable
      defibrillator. There were no deaths or heart transplantations. CONCLUSIONS:
      Overall, patients with FA have preserved cardiac function with increased mass
      throughout childhood. Because many patients who experience depressed systolic
      function show improvement in subsequent studies, evaluation for potentially
      reversible causes of heart failure should be conducted. Relative clinical
      stability during childhood and maintenance of normal systolic function into the
      second decade may be helpful for parent and patient education.

PMID- 18716707
TI  - Cardiac myxoma after treatment for childhood neuroblastoma.
AB  - An asymptomatic 13 year old with a history of neuroblastoma treated with
      chemotherapy, radiation therapy, and autologous bone marrow transplant was found
      to have a cardiac mass on screening echocardiogram. Surgical resection and
      histologic examination revealed the mass was a myxoma. After resection the
      patient made a full recovery. This report reviews the features of myxoma and
      explores the potential relationship between chemotherapy, radiation, bone marrow
      transplant and myxoma.

PMID- 18716708
TI  - Anatomical study of the plantaris tendon: reliability as a tendo-osseous graft.
AB  - PURPOSE: The purpose of this study was to investigate the insertion of the
      plantaris tendon in terms of shape, length, width and size, to define if there is
      available bony insertion for future use as reconstructive procedure in secondary
      tendon graft in hand surgery. METHODS: In 30 limbs, the plantaris tendon was
      anatomically dissected to investigate its bony attachments to the calcaneus.
      RESULTS: The plantaris was present in 29 of 30 dissections and regularly inserted
      in the calcaneus. CONCLUSIONS: The tendo-osseous plantaris graft is, according to
      this research, amenable to be used as a viable choice in reconstruction of
      secondary flexor tendon injuries related to its length shape and size and
      especially due to the bone stock adequate to strong phalanx fixation.

PMID- 18716709
TI  - Limitation of myocardial infarct size in the clinical setting: current status and
      challenges in translating animal experiments into clinical therapy.
AB  - This review takes a critical look at the current effectiveness of reperfusion
      therapy for acute myocardial infarction and at the potential for cardioprotective
      agents to improve it. Reperfusion alone limits the median value of infarct size
      to approximately 50% of the ischemic region. However, the range of infarct sizes
      is very wide, and one-fourth of these patients have more than 75% of the ischemic
      zone infarcted despite successful coronary reperfusion. Available studies suggest
      that mortality and morbidity is increased when more than 20% of the left
      ventricle is infarcted. Therefore, to be effective infarct size-limiting therapy
      would have to reduce infarction to or below this 20% target. To achieve this goal
      in the quartile of patients with the biggest infarcts the cardioprotective agent
      would have to be potent enough to reduce infarct size from its current value of
      75% of the ischemic zone to 40% or less. While ischemic preconditioning and some
      pretreatment drugs might be potent enough to achieve this goal, few of the agents
      given at the clinically relevant time of at or just before reperfusion have
      exhibited such potency. Several cardioprotective agents have recently been
      evaluated in clinical trials but their results have been disappointing. Some of
      the poor clinical trial performance may stem from study designs which fail to
      identify those patients falling within the upper quartile of infarct sizes,
      presumably the only group that would be expected to actually benefit from a
      reduction in infarct size. Other possible causes could be that co-morbidities or
      drugs patients are taking may block the pathways involved in the anti-infarct
      effect or that the drugs simply do not protect even in animal models. Few agents
      have been thoroughly tested in clinically relevant animal models prior to their
      testing in man.

PMID- 18716711
TI  - Long-term graft outcome in patients with chronic allograft nephropathy after
      immunosuppression modifications.
AB  - BACKGROUND/AIM: This retrospective study was conducted to assess the efficacy and
      safety of immunosuppression conversion on progression of chronic allograft
      nephropathy (CAN). METHODS: One-hundred and seventy-four cyclosporin (CsA)
      treated renal transplant recipients were studied. Patients were included if they
      had a biopsy-proven CAN (mild to moderate) with serum creatinine < or =3.5 mg/dL.
      Patient treatment was switched to either: (A) MMF/reduced dose CsA (MMF for
      azathioprine (Aza); n = 132); or (B) Aza/Tac for CsA (n = 42). Patient records
      were checked for graft function and survival, and for co-morbidities after
      conversion. RESULTS: Mean follow-up before conversion was 52.2 +/- 31.1 and 47.9
      +/- 27.4 months for groups A and B, respectively. There was significant
      deterioration of graft function in group B after five years (P < 0.5). Ten-year
      actuarial graft survival was 38% in group A and 19% in group B (P = 0.04). Nine
      patients (five patients and four patients in groups A and B, respectively)
      started dialysis within 12 months. Tacrolimus-treated patients had a lower
      insignificant incidence of hyperlipidemia (P = 0.05), but a significantly higher
      incidence of diabetes mellitus (P = 0.04).There was no significant change or
      difference in blood pressure between groups. CONCLUSIONS: Our results suggest
      that in patients with CAN and deteriorating allograft function, CsA minimization
      and addition of MMF achieved favorable efficacies in retarding the decline of
      graft function. Further prospective studies with larger cohorts are needed for
      validation.

PMID- 18716712
TI  - Cataract in chronic cluster headache: two case reports and review of the
      literature.
AB  - Cluster headache (CH) consists of attacks of severe, unilateral
      orbital/supraorbital/temporal pain, lasting for 15-180 min, occurring once or
      more times a day, and associated with ipsilateral conjunctival injection,
      lacrimation and other symptoms. Cataract is clouding of the lens of the eye
      causing a progressive and painless loss of vision. We describe the cases of two
      men (not relative, but with the same last name, which originates from north
      eastern Italy) that in young adult age, after years of suffering from chronic CH,
      developed cataract on the same side of the pain attacks. Patient 1 was diagnosed
      as having cataract 18 years after the onset of episodic (and subsequently
      chronic) CH. Patient 2 began suffering from chronic CH at the age of 44 years and
      after 8 years he developed cataract. This is the first report of cataract in
      patient suffering of CH and occurring in the eye affected by the pain attack.

PMID- 18716710
TI  - High frequency of BF mosaic genomes among HIV-1-infected children from Sao Paulo,
      Brazil.
AB  - HIV-1 genetic diversity information from a pediatric population is scarce. This
      study enrolled 128 children living with HIV/AIDS, 103 antiretroviral-treated and
      25 naive, from the Sao Paulo metropolitan area. Gag, pol and env regions were
      amplified, and drug resistance mutations, V3 loop, tropism and viral clades were
      evaluated. Drug resistance mutations among naive children infected by vertical
      transmission were uncommon (4.2%), whereas most ARV-experienced children showed
      extensive mutation patterns. Clade B predominated at the pol region, but the
      analysis of the three regions concatenated showed 28% with BF mosaic structures.
      The most common V3 motif was GPGR, followed by GWGR in clade B samples and GPGQ
      in clade F samples. A predicted X4 phenotype was observed in 27%, without
      correlation to HIV clade. These findings expand the limited information on
      molecular characteristics of HIV-1 among children living with HIV/AIDS in the
      area and may provide information useful for monitoring the epidemic.

PMID- 18716713
TI  - Anticoagulation for radiation-induced neurotoxicity revisited.
AB  - No effective treatment for delayed radiation-induced neurotoxicity has been
      established. Its natural course is highly variable, but spontaneous recovery has
      been well documented. Here we report our experience with therapeutic
      anticoagulation in patients with cerebral lesions (n = 3), cranial nerve lesions
      (n = 1) or myelopathy (n = 4) attributed to irradiation. Two of three patients
      with cerebral lesions and the patient with cranial nerve lesions showed a minor
      improvement of clinical symptoms. In contrast, none of the patients with
      radiation myelopathy improved. No patient suffered hemorrhage or other adverse
      effects of anticoagulation. Overall, anticoagulation therapy demonstrates only
      modest activity for delayed radiation-induced neurotoxicity in this small case
      series.

PMID- 18716714
TI  - Role of size scale of ZnO nanoparticles and microparticles on toxicity toward
      bacteria and osteoblast cancer cells.
AB  - The specific role of size scale, surface capping, and aspect ratio of zinc oxide
      (ZnO) particles on toxicity toward prokaryotic and eukaryotic cells was
      investigated. ZnO nano and microparticles of controlled size and morphology were
      synthesized by wet chemical methods. Cytotoxicity toward mammalian cells was
      studied using a human osteoblast cancer cell line and antibacterial activity
      using Gram-negative bacteria (Escherichia coli) as well as using Gram-positive
      bacteria (Staphylococcus aureus). Scanning electron microscopy (SEM) was
      conducted to characterize any visual features of the biocidal action of ZnO. We
      observed that antibacterial activity increased with reduction in particle size.
      Toxicity toward the human cancer cell line was considerably higher than
      previously observed by other researchers on the corresponding primary cells,
      suggesting selective toxicity of the ZnO to cancer cells. Surface capping was
      also found to profoundly influence the toxicity of ZnO nanoparticles toward the
      cancer cell line, with the toxicity of starch-capped ZnO being the lowest. Our
      results are found to be consistent with a membrane-related mechanism for
      nanoparticle toxicity toward microbes.

PMID- 18716715
TI  - Comparative molecular field analysis (CoMFA) and comparative molecular similarity
      indices analysis (CoMSIA) of thiazolone derivatives as hepatitis C virus NS5B
      polymerase allosteric inhibitors.
AB  - Three-dimensional quantitative structure-activity relationship (3D-QSAR) models
      for a series of thiazolone derivatives as novel inhibitors bound to the
      allosteric site of hepatitis C virus (HCV) NS5B polymerase were developed based
      on CoMFA and CoMSIA analyses. Two different conformations of the template
      molecule and the combinations of different CoMSIA field/fields were considered to
      build predictive CoMFA and CoMSIA models. The CoMFA and CoMSIA models with best
      predictive ability were obtained by the use of the template conformation from X
      ray crystal structures. The best CoMFA and CoMSIA models gave q (2) values of
      0.621 and 0.685, and r (2) values of 0.950 and 0.940, respectively for the 51
      compounds in the training set. The predictive ability of the two models was also
      validated by using a test set of 16 compounds which gave r (pred) (2) values of
      0.685 and 0.822, respectively. The information obtained from the CoMFA and CoMSIA
      3D contour maps enables the interpretation of their structure-activity
      relationship and was also used to the design of several new inhibitors with
      improved activity.

PMID- 18716716
TI  - Thyroid hormones and methylmercury toxicity.
AB  - Thyroid hormones are essential for cellular metabolism, growth, and development.
      In particular, an adequate supply of thyroid hormones is critical for fetal
      neurodevelopment. Thyroid hormone tissue activation and inactivation in brain,
      liver, and other tissues is controlled by the deiodinases through the removal of
      iodine atoms. Selenium, an essential element critical for deiodinase activity, is
      sensitive to mercury and, therefore, when its availability is reduced, brain
      development might be altered. This review addresses the possibility that high
      exposures to the organometal, methylmercury (MeHg), may perturb
      neurodevelopmental processes by selectively affecting thyroid hormone homeostasis
      and function.

PMID- 18716717
TI  - The study of Cu and Zn serum levels in idiopathic dilated cardiomyopathy (IDCMP)
      patients and its comparison with healthy volunteers.
AB  - Changes in the cupper (Cu) and zinc (Zn) concentrations have been reported
      previously in idiopathic dilated cardiomyopathy (IDCMP). As a result of
      controversial results, the aim of this study was to compare the Zn and Cu
      concentrations and Zn/Cu ratio of IDCMP patients to healthy volunteers. In
      addition, the correlation of Cu and Zn levels with age has been evaluated. The
      study population consisted of 18 IDCMP patients and 27 healthy volunteers. IDCMP
      patients had normal angiography with echocardiography supporting cardiomyopathy
      without pericardial and valvular diseases. Exclusion criteria were renal or
      hepatic insufficiency, alcohol usage, and intake of supplements containing Cu or
      Zn within 1 week ago. Cu and Zn levels have been assayed with atomic absorption
      spectrophotometry. Statistical analysis was performed with SPSS 10 software with
      independent sample t test for comparing the level of Cu and Zn of IDCMP patients
      with normal subjects and Pearson correlation to determine the correlation between
      numeric data. P < 0.05 was considered as significant differences. There was a
      trend for a lower Zn level in IDCMP patients compared to healthy volunteers.
      (0.97 +/- 0.25 mg/l vs. 1.12 +/- 0.42 mg/l, respectively). The mean Cu levels of
      IDCMP and normal subjects were 1.33 +/- 0.20 mg/l and 1.31 +/- 0.23 mg/l,
      respectively. There was a significant difference in Zn/Cu ratio among patients
      based on the NYHA classification of heart failure (P = 0.003). Age was negatively
      correlated with Zn levels in IDCMP group (P = 0.037) and positively with Cu
      levels in healthy volunteers (P = 0.012). A lower Zn level in IDCMP patients
      compared to healthy volunteers and specially a significant difference in Zn/Cu
      ratio of patients based on their NYHA classification would suggest a critical
      role of zinc and Cu imbalance in development of IDCMP.

PMID- 18716719
TI  - Measuring health literacy: moving towards a health - promotion perspective.

PMID- 18716720
TI  - Moscow Health Survey 2004--social surveying under difficult circumstances.
AB  - OBJECTIVES: The aim of this paper is to present the Moscow Health Survey 2004,
      which was designed to examine health inequalities in Moscow. In particular we
      want to discuss social survey problems, such as non-response, in Moscow and
      Russia. METHODS: Interviews, covering social and economic circumstances, health
      and social trust, of a stratified random sample of the greater Moscow population,
      aged 18+. Reasons for nonresponse were noted down with great care. Odds ratios
      (ORs) for self-rated health by gender and by six social dimensions were estimated
      separately for districts with low and high response rates. Bias due to non
      response is discussed. RESULTS AND CONCLUSIONS: About one in two (53.1%) of
      approached individuals could not be interviewed, resulting in 1190 completed
      interviews. Non-response in most Russian surveys, but perhaps particularly in
      Moscow, is large, partly due to fear of strangers and distrust of authorities.
      ORs for poor health vary significantly by gender, occupational class, education
      and economic hardship. We find no significant differences in these ORs when
      comparing districts with low and high response rates. Non-response may be a
      problem when estimating prevalence rates or population means, but much less so
      when estimating odds ratios in multivariate analyses.

PMID- 18716721
TI  - Association between acculturation and childhood vaccination coverage in migrant
      populations: a population based study from a rural region in Bavaria, Germany.
AB  - OBJECTIVES: The aim of our analysis was to investigate the association between
      acculturation and the vaccination coverage among pre-school children. METHODS: We
      performed a study of vaccination status for measles-mumps-rubella and hepatitis B
      among pre-school children, during mandatory school entry examinations, in a
      district of Bavaria, Germany, in 2004 and 2005 (N = 2,043). Prior to the
      examinations, parents were asked to fill out a self-administered questionnaire
      assessing socio-demographic information, including variables related to migration
      background (response rate 73%, N = 1,481). We used Categorical Principal
      Component Analysis (CATPCA) to create an acculturation index and assessed the
      association between the acculturation and vaccination status for both vaccines.
      RESULTS: We found no difference in vaccination status with the measles-mumps
      rubella vaccine in relation to acculturation. The coverage with at least three
      doses of hepatitis B vaccine was similar among migrants and in the indigenous
      population, but the risk of incomplete (1 or 2 doses) versus full vaccination was
      higher (OR = 2.74, 95% CI 1.34-5.61) and the risk of lacking vaccination lower
      (OR = 0.30, 95% CI 0.12-0.77) among less acculturated migrants compared to the
      indigenous population. CONCLUSIONS: For multi-dose vaccines lower acculturation
      was associated with incomplete vaccination, but the partial protection in this
      group was higher compared to indigenous population.

PMID- 18716718
TI  - Novel molecular and cellular therapeutic targets in acute lymphoblastic leukemia
      and lymphoproliferative disease.
AB  - While the outcome for pediatric patients with lymphoproliferative disorders (LPD)
      or lymphoid malignancies, such as acute lymphoblastic leukemia (ALL), has
      improved dramatically, patients often suffer from therapeutic sequelae.
      Additionally, despite intensified treatment, the prognosis remains dismal for
      patients with refractory or relapsed disease. Thus, novel biologically targeted
      treatment approaches are needed. These targets can be identified by understanding
      how a loss of lymphocyte homeostasis can result in LPD or ALL. Herein, we review
      potential molecular and cellular therapeutic strategies that (i) target key
      signaling networks (e.g., PI3K/AKT/mTOR, JAK/STAT, Notch1, and SRC kinase family
      containing pathways) which regulate lymphocyte growth, survival, and function;
      (ii) block the interaction of ALL cells with stromal cells or lymphoid growth
      factors secreted by the bone marrow microenvironment; or (iii) stimulate innate
      and adaptive immune responses.

PMID- 18716722
TI  - Social network effect on self-rated health in type 2 diabetic patients--results
      from a longitudinal population-based study.
AB  - OBJECTIVES: The aim is to analyse the association between social network and self
      rated health in a longitudinal design for persons with type 2 diabetes, comparing
      them with persons without diabetes. METHODS: The analyses are based on data from
      the population-based 'KORA-A study' conducted in the region of Augsburg
      (Germany), with data from 1990/1995 (t0) and 1998 (t1), including 164 persons
      with type 2 diabetes and 207 persons without diabetes. The social network was
      assessed by the Berkman/Syme index. RESULTS: For the type 2 diabetes group, the
      multivariate analyses show that a high score of social network at t0 is
      associated with good self-rated health at t1, even if self-rated health at t0 is
      included in the model (OR 2.69; 95% CI: 1.21-5.98). For the non-diabetes group,
      no such association was found. CONCLUSIONS: The results point towards a 'buffer
      effect' of the social network, indicating that the positive effect on health can
      be seen mostly among those who are exposed to a high level of burden, in this
      case exposed to a chronic disease such as type 2 diabetes.

PMID- 18716723
TI  - Population groups at high risk for poor oral self care: the basis for oral health
      promotion.
AB  - OBJECTIVES: Identification of population groups at high risk for poor oral self
      care in adults was needed in order to enable more focused planning of oral health
      promotion actions in Slovenia. METHODS: The study was based on the national
      health behaviour database in adults aged 25-64. Data collected in 2001 were used.
      The sample size was 15,379. The overall response rate was 64%, and 8,392
      questionnaires were eligible for oral self-care assessment. A complex indicator
      based on oral hygiene, frequency of visiting a dentist, and nutritional habits
      was derived. The outcome of interest was poor oral self-care. Logistic regression
      was used to test multivariate associations between several factors (gender, age,
      educational level, social class, etc.) and poor oral self-care. RESULTS: The
      overall prevalence of poor oral self-care was 6.9%. The odds for this outcome
      were higher for men (OR(males vs. females) = 7.49, p < 0.001), (or participants
      with the lowest educational levels (OR(uncompleted primary vs. university) =
      5.95, p < 0.001; OR(primary vs. university) = 4.95, p < 0.001), and for
      participants from the lowest social classes (OR(lower vs. upper-middle) = 6.20, p
      < 0.001; OR(labour vs. upper-middle) = 4.05, p = 0.001). CONCLUSIONS: Special
      attention should be paid to oral health promotion for men, for those with low
      educational level, and for those belonging to the lowest social classes.

PMID- 18716724
TI  - Cigarette smoking among adolescents in Thessaloniki, Greece.
AB  - OBJECTIVES: Epidemiological characteristics in tobacco smoking among adolescents
      were investigated in Thessaloniki, Greece. METHODS: The target sample was 1,221
      students coming from 15 high schools. RESULTS: Cigarette smoking was higher among
      girls than boys (40.9% vs. 34.3%). However, the percentage of boys who were
      smoking more than 20 cigarettes per day was found larger than the relevant
      percentage of girls (81.2% vs. 75% of total smokers). The boys also reported an
      earlier initiation of tobacco use (12.7 years vs. 12.9 years in girls). Physical
      activity was negatively correlated with smoking, whereas drinking alcohol and low
      parental education were positively correlated with smoking. CONCLUSIONS: Health
      promotion programs should be instituted not only during adolescence, but rather
      before the age of 14.

PMID- 18716725
TI  - Determinants of university students physical exercise: a study from Lebanon.
AB  - BACKGROUND: Studies to assess the patterns of physical exercise among University
      students in Lebanon are lacking. The current study looks at the prevalence of
      physical exercise among university students in Beirut and predictors of
      performing physical exercise. METHODS: In a cross-sectional study, a
      proportionate random sample of university students selected from five major
      universities were asked to complete a self-administered questionnaire related to
      physical exercise, demographic, scholastic, and health risk behavioral
      characteristics. Physical exercise was divided into: "No"" (< 0.5 h) and "Yes" (>
      0.5 h) per week. Chi-square tests and binary regression were conducted to
      determine the predictors of performing physical exercise. RESULTS: Of 2,013
      students, only 26.4% engaged in physical exercise. Predictors of performing
      physical exercise for males, were adoption of exercise as the method of weight
      control, while for females, they were living abroad, drinking excessive alcohol,
      and adopting exercise for weight control. CONCLUSION: The prevalence of physical
      exercise among Lebanese university students is low. Weight control remains the
      most important predictor of physical activity in males and females.

PMID- 18716726
TI  - Associations of behavioural, psychosocial and socioeconomic factors with over-
      and underweight among German adolescents.
AB  - OBJECTIVES: The prevalence of overweight and obesity has dramatically increased
      in western societies. This paper examines behavioural, psychosocial and
      socioeconomic factors associated with overweight and underweight among
      adolescents in Germany. METHODS: Data from the German part of the 2001/02 Health
      Behaviour in School-aged Children (HBSC) survey, composed of 5,650 respondents
      aged 11 to 17 years were analysed. Body mass index (BMI) was calculated based on
      self-reported weight and height. The overweight category was defined as BMI
      within or above the 90th percentile of specific BMI values for gender and age in
      the German national sample. The underweight category was defined as BMI within or
      below the 10th percentile of this sample. A multinomial logistic regression model
      was used to investigate the association between behavioural, psychosocial and
      socioeconomic factors and BMI categories. RESULTS: 9.5% of the boys and 5.4% of
      the girls were classified as overweight. The prevalence of underweight was 12.6%
      among boys and 19.1% among girls. Several factors were associated with over-
      and/or underweight in the bivariate analysis, showing different patterns for
      gender and BMI categories. In the multivariable model only low family affluence,
      high sedentary behaviour, and being bullied (for girls only) remained positively
      associated with being overweight. Being underweight was negatively associated
      with higher age and low parental occupation; it differed also by region.
      CONCLUSION: Despite several variables being associated with overweight and
      underweight in bivariate models, only three factors remained associated with
      overweight in multivariable analysis. Other considered variables did not have
      independent associations with the outcome, but still could be included in
      respective causal pathways. Our results suggest that preventive strategies
      focussing on students of low socio-economic status and the avoidance of sedentary
      behaviours could help to address issues of overweight and obesity.

PMID- 18716728
TI  - Shoulder arthrodesis with a reconstruction plate.
AB  - From 1995 to 2005, arthrodesis with a reconstruction plate was performed for
      eight shoulders. The average follow-up period was 44 months. The indications for
      shoulder arthrodesis were joint destruction as a sequel of tuberculous arthritis,
      malignant bone tumour, pyogenic arthritis, failed arthrodesis and paralysis of
      the brachial plexus. The evaluation criteria included bony union and pain. Two
      cases of malignant tumour required an homologous bone graft due to severe bone
      deficit--a fracture that occurred in the distal part of the arthrodesed shoulder
      after removing the plate. With the exception of these two cases, severe pain or
      other complications did not occur in any other case. Shoulder arthrodesis with a
      reconstruction plate was judged to be a useful method for glenohumeral salvage in
      cases without severe bone deficit. Further, additional treatment methods should
      be considered to prevent fracture that may occur as a result of severe bone
      deficit.

PMID- 18716729
TI  - Prevalence of subjective voice impairment in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) might lead to voice impairment through several
      mechanisms but its prevalence has been little investigated. RA patients attending
      a rheumatology outpatient clinic had joint assessments and completed the Voice
      Handicap Index-10 (VHI-10). A comparator group consisted of patients attending
      the department with other diseases. Seventy-three patients with RA and 73
      comparators were recruited. Four patients with RA (5%) and one comparator (1%)
      had significantly abnormal VHI-10 scores. RA patients with a Disease Activity
      Score 28 >3.2, indicating more active disease, had significantly higher VHI-10
      scores. A low prevalence of self-reported voice handicap occurs in RA and
      associates with more active disease.

PMID- 18716730
TI  - Could intravenous cyclosporin A be an effective therapeutic strategy in pulmonary
      hemorrhage associated with Henoch-Schonlein purpura? Comment on: Pulmonary
      hemorrhage associated with Henoch-Schonlein purpura in a child [Clin Rheumatol
      27(6):803-805].

PMID- 18716731
TI  - Complete resolution of a mitral valve vegetation with anticoagulation in
      seronegative antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is a disorder characterized by recurrent venous
      or arterial thrombosis and/or fetal loss; involvement of cardiac valves is also
      seen. A seronegative variant has been described previously. We report a case of a
      woman with recurrent pregnancy loss, prior strokes, and a negative workup for
      known antiphospholipid antibodies. During her current pregnancy, she presented
      with acute stroke and mitral valve vegetation. Her workup for antiphospholipid
      syndrome and other thrombophilias remained negative even after the stroke. Her
      mitral valve vegetation resolved completely with aspirin, heparin, and warfarin.
      We believe this to be the first report of complete resolution of valvular
      vegetation with antiplatelet and anticoagulant therapy alone in a patient with
      seronegative antiphospholipid syndrome. Moreover, this appears to be the first
      report of stroke associated with this condition.

PMID- 18716732
TI  - Left ventricular diastolic function evaluated with tissue Doppler imaging in
      children with familial Mediterranean fever.
AB  - The aim of this study was to assess the left ventricular diastolic function using
      conventional echocardiography and tissue Doppler imaging in children with
      familial Mediterranean fever. This study included 29 (13 males and 16 females)
      patients and 30 healthy subjects as controls. Body mass index was calculated and
      arterial blood pressure was monitored. After an overnight fast, venous blood
      samples were taken and serum amyloid A protein, C-reactive protein, serum-fasting
      glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol,
      very low density lipoprotein cholesterol, and serum low-density lipoprotein
      cholesterol levels were measured. A complete 2-dimensional, M-mode, pulse wave
      Doppler, and pulse wave tissue Doppler echocardiographic examination was
      performed. There were no significant differences between the groups regarding
      age, body mass index values, systolic and diastolic blood pressures, heart rates,
      serum-fasting glucose, total cholesterol, triglycerides, high-density lipoprotein
      cholesterol, very low density lipoprotein cholesterol, and serum low-density
      lipoprotein cholesterol. Serum levels of inflammatory markers were higher in
      patients' group (C-reactive protein and serum amyloid A protein levels were 10.84
      mg/dl, 22.32 mg/l in patients' group, respectively, and 4.11 mg/dl, 3.65 mg/l,
      respectively, in the healthy controls.) Peak mitral A wave, E and A wave ratio
      differed significantly in both groups. There were statistically significant
      differences regarding parameters observed by tissue Doppler imaging such as E'm,
      A'm, E'm, and A'm ratio between patients' group and controls. Tissue Doppler
      imaging provided additional information on left ventricular diastolic function.
      While systolic functions were in normal range, some of the diastolic function
      parameters were impaired in patients with familial Mediterranean fever during
      childhood.

PMID- 18716733
TI  - Treatment of refractory juvenile dermatomyositis with tacrolimus.
AB  - We report the clinical course of three patients with refractory juvenile
      dermatomyositis (JDM) who were treated with tacrolimus. All three children had
      extensive skin disease and severe muscle weakness and were corticosteroid
      dependent. All three patients showed impressive improvement of mainly the
      cutaneous lesions. Furthermore, overall disease activity decreased, all children
      became more physically active, and corticosteroid treatment could be tapered.
      However, none of the patients showed recovery of muscle strength, which was most
      likely due to irreversible muscle damage related to the long-standing myositis
      and/or high-dose steroid treatment. Patients were followed up for 7 to 9 months
      after the introduction of tacrolimus. No adverse effects were seen. These cases
      demonstrate that tacrolimus has beneficial effects in children with refractory
      JDM, especially in those with severe cutaneous manifestations.

PMID- 18716734
TI  - Trial using multiple micronutrient food supplement and its effect on cognition.
AB  - OBJECTIVE: To test the efficacy of a multiple micronutrient food supplement
      (MMFS) on the nutrition status of school children and its effect on cognition.
      METHODS: A MMFS was developed containing chelated ferrous sulphate and
      microencapsulated vitamin A, B2, B6, B12, folic acid, niacin, calcium
      pantothenate, vitamin C, vitamin E, lysine and calcium and the efficacy of the
      MMFS was assessed in 7-11 year old school children in Chennai, India by a pre
      post test design. In the experimental group (N=51), the food in the school
      kitchen was cooked with the MMFS for the residential school children for a period
      of one year. The control group (N=72) consisted of day scholars who did not eat
      at the school. Hemoglobin, red blood cell count and hematocrit were measured at
      baseline and at the end of the study (after one year). A battery of 7 memory
      tests (The personal information test, the Mann-Suiter Visual memory screen for
      objects, The digit span forward test, The digit span backward test, The delayed
      response test, The Benton Visual Retention Test and The Cattells retentivity
      test), one test for attention and concentration (Letter cancellation test) and
      one test for intelligence (Ravens's coloured progressive matrices) were
      administered to all the children at baseline and endline. RESULTS: It was seen
      that there was a significant (P<0.05) improvement in the experimental group in
      hemoglobin, hematocrit and red cell count whereas in the control group there was
      a statistically significant decline(P<0.05) in hemoglobin and red cell count. In
      5 tests out of the 7 memory tests and in the letter cancellation test for
      attention, the mean change in scores in the experimental group is significantly
      more (P<0.05) than the control group. There was no significant improvement in the
      overall intelligence as seen in the Ravens progressive matrices between the
      experimental and control groups at endline. CONCLUSION: The study shows that the
      MMFS is effective in improving the nutrition status and cognition in children.

PMID- 18716735
TI  - Correlation of thyroid and growth hormones to chromosomal instability in Egyptian
      Fanconi anemia patients.
AB  - OBJECTIVE: Fanconi anemia (FA) is a rare inherited genomic instability syndrome
      and usually associated with endocrine dysfunctions. We aimed to assess the
      diagnostic standards of chromosomal instability in FA and to correlate the
      breakage frequency with the severity of endocrinal dysfunctions. METHODS: Twenty
      seven FA patients were randomly selected from Hematology Unit of Mansoura
      University Children's Hospital; their mean age 8.8 yr. Sixteen normal children
      matched for age and sex were used as controls. Cytogenetic studies included
      peripheral blood lymphocyte cultures using phytohemagglutinin to obtain
      chromosomal spreads. Chromosomal breakage was induced by (i) Diepoxybutane 0.1
      mug/ml. (ii) Mitomycin C 0.1 microg/ml. (iii) Irradiation of cultures to four
      radiation doses; 75, 150, 300 and 400 rads (rad1, rad2, rad3 and rad4
      respectively). Chromosomal aberrations were scored from the previous 6 cultures
      besides a culture for spontaneous chromosomal breakage; then mean chromosomal
      breakage was calculated for the seven cultures. Endocrinal evaluation included
      quantitative determination of thyroid stimulating hormone (TSH) and
      tetraiodothyronine (T4), serum growth hormone (GH), insulin like growth factor-1
      (IGF-1) and insulin levels. RESULTS: Chromosomal breakage was found to be
      significantly higher in patients than control when induced by Diepoxybutane (p =
      0.003), Mitomycin (p = 0.001), rad3 (p = 0.043) and rad4 (p = 0.001). Mean
      chromosomal breakage was significantly negative correlated to head circumference
      (r = -0.57) and GH level (r = -0.50), with no significant correlation to other
      hormonal parameters. Mitomycin and rad4 were found more accurate than DEB test
      for diagnosis of FA in suspected cases. CONCLUSION: Correction of the frequently
      associated hormonal dysfunction (reduced GH and T4) should be considered in the
      treatment discipline of FA patients to improve their final height.

PMID- 18716736
TI  - Behavior in children with Down syndrome.
AB  - OBJECTIVE: To highlight the differences in behaviors in children with diagnosis
      of Down syndrome. METHOD: Eight children with Down syndrome who displayed
      autistic features were compared with eight Down syndrome children without
      autistic features. These children were randomly selected and were matched for age
      and level of retardation. Standardized Psychological tests were administered to
      tap the behavioral differences. Mann-Whitney U test was used for significance of
      difference between both the groups. RESULTS: Down syndrome children without
      Autism Spectrum Disorder had better communication and socialization skills than
      children with Down syndrome with Autism Spectrum Disorder. Down syndrome children
      with Autism Spectrum Disorder displayed more restricted repetitive and
      stereotyped patterns of behaviors, interests and activities. CONCLUSION: Our
      findings indicate that Autism Spectrum Disorder manifests as a distinct
      behavioral phenomenon in Down syndrome. Hence it is important for professionals
      to consider the possibility of a dual diagnosis which will entitle the child to a
      more specialized and effective educational and intervention services.

PMID- 18716737
TI  - Admission time and mortality rates.
AB  - OBJECTIVE: The objective of this study was to determine whether there there are
      any associations between time of admission and mortality rates in the pediatric
      intensive care unit. METHODS: We analyzed retrospectively 210 consecutive
      admissions to the PICU from November 2005 to April 2006 for patients aged 1 mth
      to 18 yr. RESULTS: There was no significant difference for overall mortality
      rates between weekend and weekday admissions (12.2% vs 17.4%, p=0.245), and
      daytime and evening admissions (11.3 % vs 15.4%, p=0.254). There was also no
      significant difference between different admission times for within 24 hours, 48
      hours and 72 hours mortality rates. CONCLUSIONS: In respect of the overall
      mortality rates, it can be said that in a closed system PICU management under the
      control of a pediatric intensivist there is no association between time of
      admission and mortality rates.

PMID- 18716738
TI  - Neuromuscular junctional disorders.
AB  - Neuromuscular junctional disorders (NMJ) in children are distinct entity. They
      may be acquired or hereditary. They pose problem in diagnosis because of the
      higher occurrence of sero negative Myasthenia Gravis (MG) cases in children. The
      identity of MusK antibody positivity in a good percentage of sero negative cases
      further adds to problems in diagnosis. The Congenital Myasthenic Syndrome (CMS)
      which are rare disorders of hereditary neuromuscular transmission (NMT) has to be
      differentiated because immunotherapy has no benefit in this group. Molecular
      genetic studies of these diseases helps to identify specific type of CMS which is
      important as other drugs like Fluoxetine, Quinidine are found to be effective in
      some. In infancy, all can manifest as floppy infant syndrome. The important key
      to diagnosis is by detailed electrophysiological studies including repetitive
      nerve stimulation at slow and high rates and its response to anticholinesterases
      and estimation of Acetyl choline receptor antibodies. Other causes of
      neuromuscular transmission defects viz. snake venom poisoning and that due to
      drugs are discussed.

PMID- 18716739
TI  - Cleft palate habilitation.
AB  - Presurgical Orthopaedics is any treatment that alters the position of the
      segments of cleft maxilla in infancy prior to lip and palate reconstruction.
      There are different approaches, with different mechanics, seeking and achieving
      different end results. This article describes PNAM, a current approach to the
      traditional method of presurgical infant orthopaedics for patients with
      unilateral and bilateral clefts of lip and palate. The goal of PNAM is to align
      and approximate the alveolar cleft segments while at the same time achieving
      correction of nasal cartilage and soft tissue deformity.

PMID- 18716740
TI  - Randomized double blinded controlled trial to evaluate the efficacy and safety of
      Bifilac in patients with acute viral diarrhea.
AB  - OBJECTIVE: To evaluate the efficacy and safety of Bifilac on reducing the
      episodes (frequency) and duration of diarrhea induced by rotaviral infection and
      to evaluate the efficacy of Bifilac to ameliorate the associated symptoms like
      dehydration and duration of rotaviral shedding in faeces. METHODS: 80 children
      aged between 3 months and 3 years were enrolled and divided into 2 groups, one
      group received standard therapy + placebo, the other group received standard
      therapy + probiotic (Bifilac) randomly. Children assessed for frequency and
      duration of diarrhea. Degree of dehydration, duration and volume of oral
      rehydration salt [ORS] therapy, duration and volume of Intra venous fluids and
      duration of rotaviral shedding. RESULTS: When compared to the placebo, Bifilac
      showed clinical as well as statistically significant reduction in Number of
      episodes (frequency) of diarrhea in a day, mean duration of diarrhea (in days)
      degree of dehydration, duration and volume of oral rehydration salt [ORS]
      therapy, duration and volume of intravenous fluid [IVF] therapy, duration of
      rotaviral shedding (P<0.01). CONCLUSION: The synbiotic, bifilac, appears to be a
      safe and very effective adjuvant in the management of acute rotaviral diarrhea.

PMID- 18716742
TI  - Blood component therapy.
AB  - The blood component support in pediatric patients is more challenging as compared
      to adult patients, as such, a thorough understanding of various blood components
      and indications for each is critical when making the decision for transfusion.
      Transfusion needs in pediatric group parallel the changes that accompany the
      transitions from fetus to neonate, neonate to infant, and throughout childhood.
      Modified or unmodified blood components viz. red blood cells, platelets,
      granulocytes, fresh frozen plasma and cryoprecipitate are required for
      transfusion support in pediatric population. In general, fetuses and infants
      younger than 4 months of age have specialized transfusion requirements whereas
      transfusion of infants older than 4 months and children parallels those for
      adults. Transfusion practices differ widely among pediatric care units depending
      upon individual preferences, hospital transfusion policy and resource
      availability. There is a need to implement best transfusion practices and despite
      the lack of firm evidences, existing pediatric transfusion guidelines can help
      pediatric care providers in their decisions related to component transfusion.

PMID- 18716743
TI  - Immune thrombocytopenic purpura.
AB  - Immune thrombocytopenic purpura (ITP) is the commonest cause of sudden onset
      thrombocytopenia in a healthy child. The condition is frequently preceded by a
      viral infection. The hematological parameters are essentially normal except a low
      platelet count. Bone marrow examination is not routinely indicated except in
      specific situations. The pros and cons of drug treatment have been discussed as
      the disease is benign with excellent prognosis in majority of the cases. The
      various treatment options including low and high dose steroids, intravenous
      immunoglobulins and anti D have been discussed at length with other modalities of
      treatment and role of splenectomy. Current therapeutic options with rituximab and
      other drugs for stimulating platelet production in chronic cases have also been
      included in discussion.

PMID- 18716744
TI  - Myelodysplastic syndrome.
AB  - Pediatric myelodysplastic syndrome (MDS), though rare, constitutes a distinct
      entity quite different from adult MDS. They have unique clinical features,
      aggressive clinical course with an overall mean survival of only 9.9 months. A
      pediatric approach to the WHO classification has become necessary since the WHO
      classification of MDS has failed to address the uniqueness of pediatric MDS. A
      new prognostic system also needs to be evolved since the international prognostic
      system has limited prognostic impact in children. Intensive chemotherapy such as
      the one used in de novo-acute myeloid leukemia (AML) leads to complete remission
      in some children and this may be the treatment of choice in pediatric MDS.

PMID- 18716745
TI  - Disseminated intravascular coagulation: current concepts.
AB  - Disseminated intravascular coagulation (DIC) is an acquired disorder in which
      normal hemostatic balance is disturbed. There is excessive thrombin formation
      leading to fibrin deposition in microcirculation and consequent ischemic organ
      damage. The etiology is multifactorial. A number of medical, surgical,
      oncological and obstetrical conditions can cause DIC. The diagnosis is
      essentially clinical supported by laboratory parameters and a scoring system
      based on these. The mainstay of treatment is correction of underlying cause and
      hemostatic support with replacement of coagulation factors. The role of heparin
      therapy and other therapeutic options including activated protein C, antithrombin
      III etc. have also been discussed.

PMID- 18716746
TI  - Current trends in the management of beta thalassemia.
AB  - The management of Beta Thalassemia, the commonest form of hemolytic anemia in
      children, has changed significantly in the last few years. With the availability
      of better transfusion regimen, iron chelation therapy, proper management of
      complications and good supportive care, it is now possible for a thalassemic
      child to have a near normal life span with a good quality of life.

PMID- 18716747
TI  - Bilateral fibular hemimelia with recto-vestibular fistula associated with
      amniotic bands.
AB  - Fibular Hemimelia is a rare congenital disorder of deficiency to complete absence
      of fibula. It has been associated with post axial skeletal anomalies like
      shortening of femur, absence of lateral rays of foot and syndactyle, polydactyle
      etc. We report this case because of associated amniotic constriction bands over
      both the forearm, suggesting amniotic bands may be one of the causal factors of
      Fibular Hemimelia due to insult to the growing limb bud.

PMID- 18716748
TI  - Unusual lymphocytosis with systemic lupus erythematosus.
AB  - A 15-year-old boy with systemic lupus erythematosus, who on a follow up visit
      complained of recurrent episodes of fever, easy fatiguability, and seizures.
      Investigations revealed lymphocytosis (95%), anemia, and a positive PCR for
      cytomegalovirus (CMV). Electron microscopy of the lymphocytes revealed
      intranuclear inclusion bodies supporting the diagnosis of CMV infection. The
      child was treated with ganciclovir and discharged. At discharge the child was
      afebrile. However, lymphocytosis persisted even after 9 months of discharge.
      Repeated screening for possible lymphoreticular malignancy was negative. It is
      likely that lymphocytosis in this child was due to persistence of CMV infection
      in host cells leading to continued provocation of the host immune system.

PMID- 18716749
TI  - Vitamin B12 and homocysteine status in asymptomatic Indian toddlers.
AB  - Low serum vitamin B(12) (V B(12)) and hyperhomocysteinemia have been reported in
      asymptomatic Asian Indian men. We studied the prevalence of V B(12) deficiency
      and hyperhomocysteinemia in 51 asymptomatic toddlers, from Pune, India. V B(12)
      levels were low and total serum homocysteine was high in 14% and homocysteine
      levels were significantly higher in boys. Programming for cardiovascular risk in
      adulthood possibly starts at a very young age through the homocysteine axis.

PMID- 18716750
TI  - Amniotic band syndrome.

PMID- 18716751
TI  - Statement on publishing clinical trials in Indian biomedical journals.

PMID- 18716752
TI  - [Burn trauma. Part 1: pathophysiology, preclinical care and emergency room
      management].
AB  - Severe burn injuries are rare and represent less than 1% of all medical
      emergencies. At the scene of the accident self-protection is important. The
      progress of thermal injury should be stopped, while cold water therapy is usually
      not indicated as the resulting hypothermia severely reduces the prognosis. A
      thorough body check reveals the burn size, depth and presence of co-injuries.
      Volume depletion is the main pathophysiological reason for burn shock. Early
      infusion therapy is of prognostic significance. Sufficient analgesia has to be
      established. Intubation is not generally indicated even with extensive burns,
      whereas early intubation can be life-saving in the case of circular thoracic
      burns, face burns and inhalation trauma. Local or systemic administration of
      corticosteroids is not indicated. Transfer to a specialized burn unit depends on
      burn size and depth. Emergency room management includes stabilization of vital
      functions, evaluation of co-injuries and initiation of the specific surgical and
      intensive care therapy.

PMID- 18716753
TI  - [Postbariatric plastic surgery].
AB  - Approximately 1.7 billion people around the world are defined as being overweight
      or obese. Various surgical options to treat obesity have quite recently been
      developed. Following efficient and lasting weight loss, up to one-third of the
      patients will require plastic and reconstructive surgery. Plastic surgery will
      thus be the final part of a modern bariatric treatment plan. Postbariatric
      plastic surgery interventions do not treat obesity but rather remove excess skin
      and restore the normal body contour and function of the bariatric patient. The
      presented work summarizes current concepts and limitations in modern plastic and
      reconstructive surgery of the bariatric patient population.

PMID- 18716755
TI  - Cloning and characterization of phosphorus starvation inducible Brassica napus
      PURPLE ACID PHOSPHATASE 12 gene family, and imprinting of a recently evolved MITE
      minisatellite twin structure.
AB  - Purple acid phosphatase (PAP) is important for phosphorus assimilation and in
      planta redistribution. In this study, seven Brassica napus PAP12 (BnPAP12) genes
      orthologous to Arabidopsis thaliana PAP12 (AtPAP12) are isolated and
      characterized. NCBI BLASTs, multi-alignments, conserved domain prediction, and
      featured motif/residue characterization indicate that all BnPAP12 members encode
      dimeric high molecular weight plant PAPs. BnPAP12-1, BnPAP12-2, BnPAP12-3 and
      BnPAP12-7 (Group I) have six introns and encode 469-aa polypeptides structurally
      comparable to AtPAP12. BnPAP12-4 and BnPAP12-6 (Group II) have seven introns and
      encode 526-aa PAP12s. Encoding a 475-aa polypeptide, BnPAP12-5 (Group III) is
      evolved from a chimera of 5' part of Group I and 3' part of Group II. Sequence
      characterization and Southern detection suggest that there are about five BnPAP12
      alleles. Homoeologous non-allelic fragment exchanges exist among BnPAP12 genes.
      BnPAP12-4 and BnPAP12-6 are imprinted with a Tourist-like miniature inverted
      repeat transposable element (MITE) which is tightly associated with a novel
      minisatellite composed of four 36-bp tandem repeats. Existing solely in B.
      rapa/oleracea lineage, this recently evolved MITE-minisatellite twin structure
      does not impair transcription and coding capacity of the imprinted genes, and
      could be used to identify close relatives of B. rapa/oleracea lineage within
      Brassica. It is also useful for studying MITE activities especially possible
      involvement in minisatellite formation and gene structure evolution. BnPAP12-6 is
      silent in transcription. All other BnPAP12 genes basically imitate AtPAP12 in
      tissue specificity and Pi-starvation induced expression pattern, but divergence
      and complementation are distinct among them. Alternative polyadenylation and
      intron retention also exist in BnPAP12 mRNAs.

PMID- 18716754
TI  - Breast cancer epigenetics: normal human mammary epithelial cells as a model
      system.
AB  - DNA hypermethylation and histone modifications are two critical players involved
      in epigenetic regulation and together play an important role in silencing tumor
      suppressor genes in all cancers, including breast cancer. One of the major
      challenges facing breast cancer researchers is the problem of how to identify
      critical genes that are epigenetically silenced early in cancer initiation as
      these genes provide potential early diagnostic and/or therapeutic targets for
      breast cancer management. This review will focus on compelling evidence that
      normal Human Mammary Epithelial Cells (HMECs) that escape senescence in culture
      mimic genetic and epigenetic events occurring in early breast cancer, and provide
      a valuable system to delineate the early steps in epigenetic deregulation that
      often occur during transition of a normal breast cell to a premalignant cell. In
      particular, this model system has been used to investigate the relationship
      between gene silencing, DNA methylation, histone modifications, and polycomb
      association that may occur early in oncogenic transformation.

PMID- 18716756
TI  - The involvement of sortase A in high virulence of STSS-causing Streptococcus suis
      serotype 2.
AB  - Sortase A (SrtA), originally identified as a transpeptidase in Staphylococcus
      aureus, plays key roles in full virulence of pathogenic bacteria. In silico
      genome-wide search suggested a srtA homologue from 05ZYH33, a Chinese human
      isolate of streptococcal toxic shock syndrome (STSS)-causing Streptococcus suis
      serotype 2 (S. suis 2, SS2). An isogenic srtA mutant (DeltasrtA) of 05ZYH33
      strain was obtained by homologous recombination. Immunofluorescence analysis
      revealed that two known virulence-associated surface proteins featuring Leu-Pro-X
      Thr-Gly motif, muramidase-released protein and surface antigen one, were absent
      in the DeltasrtA. Piglet infection experiments showed that deletion of srtA
      attenuated the full virulence of 05ZYH33 strain, and impaired its colonizing
      potential in specific organs. Furthermore, the DeltasrtA displayed significant
      reduction in adherence to human cells (Hep-2 and human umbilical vein endothelial
      cells). Collectively, we concluded that SrtA was involved in the virulence
      manifestation of STSS-causing SS2.

PMID- 18716757
TI  - Biosynthesis of the respiratory formate dehydrogenases from Escherichia coli:
      characterization of the FdhE protein.
AB  - Escherichia coli can perform two modes of formate metabolism. Under respiratory
      conditions, two periplasmically-located formate dehydrogenase isoenzymes couple
      formate oxidation to the generation of a transmembrane electrochemical gradient;
      and under fermentative conditions a third cytoplasmic isoenzyme is involved in
      the disproportionation of formate to CO(2) and H(2). The respiratory formate
      dehydrogenases are redox enzymes that comprise three subunits: a molybdenum
      cofactor- and FeS cluster-containing catalytic subunit; an electron-transferring
      ferredoxin; and a membrane-integral cytochrome b. The catalytic subunit and its
      ferredoxin partner are targeted to the periplasm as a complex by the twin
      arginine transport (Tat) pathway. Biosynthesis of these enzymes is under control
      of an accessory protein termed FdhE. In this study, it is shown that E. coli FdhE
      interacts with the catalytic subunits of the respiratory formate dehydrogenases.
      Purification of recombinant FdhE demonstrates the protein is an iron-binding
      rubredoxin that can adopt monomeric and homodimeric forms. Bacterial two-hybrid
      analysis suggests the homodimer form of FdhE is stabilized by anaerobiosis. Site
      directed mutagenesis shows that conserved cysteine motifs are essential for the
      physiological activity of the FdhE protein and are also involved in iron
      ligation.

PMID- 18716758
TI  - Muscarinic cholinergic modulation of synaptic transmission and plasticity in rat
      hippocampus following chronic lead exposure.
AB  - The cholinergic system is believed to be associated with learning and memory
      functions. Lead (Pb2+) is a well-known neurotoxic metal that causes irreversible
      damage to the central nervous system (CNS). To investigate whether Pb2+
      interferes with cholinergic modulation, we examined the effects of carbachol
      (CCh), a muscarinic cholinergic agonist, on synaptic transmission and plasticity
      in the CA1 area of the hippocampus of developmentally Pb2+-exposed rats. The
      results showed that: (1) In both control and Pb2+-exposed rats, 0.1 microM CCh
      significantly enhanced tetanus-induced long-term potentiation (LTP), while 5
      microM CCh induced a reversible depression of field excitatory postsynaptic
      potentials (fEPSPs). However, both the enhancement of LTP and depression of
      fEPSPs were significantly smaller in Pb2+-exposed rats than in controls,
      suggesting that the extent of the effect of CCh on the cholinergic system was
      depressed by Pb2+. (2) In Pb2+-exposed rats, the enhancement of LTP induced by
      0.1 microM CCh was attenuated by pirenzepine, a M1AChR antagonist, but was not
      affected by methoctramine tetrahydrochloride (M-105), a M2/4AChR antagonist. The
      depression of fEPSPs induced by 5 microM CCh was reduced by either pirenzepine or
      M-105. (3) Furthermore, paired-pulse facilitation (PPF) was not affected by 0.1
      microM CCh in control and Pb2+-exposed rats but was increased by 5 microM CCh in
      either group; the increase in PPF was less pronounced in Pb2+-treated when
      compared to control rats. These results suggested that cholinergic modulation
      could be impaired by Pb2+, and this kind of impairment might occur via different
      mAChR subtypes. Our study delineated the effects of Pb2+ on muscarinic
      modulation, and this might be one of the underlying mechanisms by which Pb2+
      impairs learning and memory.

PMID- 18716759
TI  - Effects of curcumin on ethanol-induced hepatocyte necrosis and apoptosis:
      implication of lipid peroxidation and cytochrome c.
AB  - Ethanol-induced hepatocyte necrosis and apoptosis are valid in vitro models to
      investigate the modulatory effects of hepatoprotective/toxic agents such as
      curcumin. In this study, suspension and monolayer cultures of isolated rat
      hepatocytes were used. Levels of trypan blue uptake, reduced glutathione, and
      lipid peroxidation were quantified. Chromatin condensation, caspase-3 activity,
      and cytochrome c extramitochondrial translocation were also evaluated. Results
      revealed that curcumin did not protect against either ethanol-induced necrosis or
      glutathione depletion. Neither did curcumin reduce caspase-3 activation nor
      chromatin condensation. In contrast, curcumin induced glutathione depletion,
      caspase-3 activation, necrosis, and apoptosis. Fortunately, all tested curcumin
      concentrations (1 microM-10 mM) diminished the ethanol-induced lipid
      peroxidation. In addition, 1 microM curcumin decreased cytochrome c translocation
      in hepatocyte monolayers. In conclusion, low concentrations of curcumin may
      protect hepatocytes by reducing lipid peroxidation and cytochrome c release.
      Conversely, higher concentrations provoke glutathione depletion, caspase-3
      activation, and hepatocytotoxicity.

PMID- 18716760
TI  - Nicotine effects on learning in zebrafish: the role of dopaminergic systems.
AB  - RATIONALE: Nicotine improves cognitive function in a number of animal models
      including rats, mice, monkeys, and recently, zebrafish. The zebrafish model
      allows higher throughput and ease in discovering mechanisms of cognitive
      improvement. MATERIALS AND METHODS: To further characterize the neural bases of
      nicotine effects on learning in zebrafish, we determined changes in dopaminergic
      systems that accompany nicotine-enhanced learning. RESULTS: Nicotine improved
      learning and increased brain levels of dihydroxyphenylacetic acid (DOPAC), the
      primary dopamine metabolite. There was a significant correlation between choice
      accuracy and DOPAC levels. The nicotinic antagonist mecamylamine blocked the
      nicotine-induced increase in DOPAC concentrations, in line with our previous
      finding that mecamylamine reversed nicotine-induced learning improvement.
      CONCLUSIONS: Dopamine systems are related to learning in zebrafish; nicotine
      exposure increases both learning rates and DOPAC levels; and nicotinic antagonist
      administration blocks nicotine-induced rises in DOPAC concentrations. Rapid
      cognitive assessment of drugs with zebrafish could serve as a useful screening
      tool for the development of new therapeutics for cognitive dysfunction.

PMID- 18716762
TI  - Thermoresponsive polymeric gel as a medium for examining interactions between
      dsDNA and an anticancer drug.
AB  - A piece of dry N-isopropylacrylamide polymer was soaked in phosphate buffer to
      obtain a hydrogel which was then employed in the examination of interactions
      between an anticancer drug C-1311 (5-diethylaminoethyl-amino-8
      hydroxyimidazoacridinone) and dsDNA. dsDNA was introduced into the polymer at the
      polymerization stage. The drug was added to the buffer. Using the volume phase
      transition of the gel at 40 degrees C, the unbound drug could be determined in
      the solution released during the transition, which made the calculations more
      reliable. The interaction parameters were calculated using the McGhee and von
      Hippel model. It appeared that in the gel medium, the interaction between the
      drug and dsDNA is spatially limited, since the number of binding units of the
      polymer chain occupied by one drug molecule was found to be one, while it was two
      in the regular buffer solution.

PMID- 18716761
TI  - A placebo-controlled study of sildenafil effects on cognition in schizophrenia.
AB  - BACKGROUND: Phosphodiesterase 5 (PDE5) inhibitors increase cyclic guanosine
      monophosphate (cGMP) concentrations in the intracellular pathway activated by N
      methyl-D-aspartic acid receptors which is believed to mediate long-term
      potentiation and memory consolidation. The PDE5 inhibitor sildenafil has been
      shown to enhance memory in animal models. In addition, neuronal nitric oxide
      synthase, another component of the NMDA/nitric oxide/cGMP intracellular pathway,
      has been reported to be dysregulated in schizophrenia patients. MATERIALS AND
      METHODS: Seventeen adult schizophrenia outpatients treated with a stable dose of
      antipsychotic received a single oral dose of placebo, sildenafil 50 mg, and
      sildenafil 100 mg in random order with a 48-h interval between administrations.
      Psychiatric symptom ratings and a cognitive battery were performed at baseline
      and 1 hour following each administration of the study drug. In addition, memory
      consolidation was examined by testing recall 48 h later, prior to the next
      administration of the study drug. RESULTS: Fifteen subjects completed all three
      treatment conditions. One subject developed irritability and required
      hospitalization 2 days after receiving sildenafil 100 mg. Neither dose of
      sildenafil significantly affected cognitive performance or symptom ratings
      compared to the placebo. CONCLUSION: Despite evidence for cognitive-enhancing
      effects of sildenafil in animal models, the strategy for treating putative NMDA
      receptor-mediated memory deficits in schizophrenia with sildenafil 50 and 100 mg
      was not successful. It is possible that the doses used in this study were not
      optimal or that repeated dosing may be necessary to achieve therapeutic effects.
      Agents under development that inhibit other subtypes of PDE remain promising for
      schizophrenia and dementia.

PMID- 18716763
TI  - Effects of saccadic adaptation on visual localization before and during saccades.
AB  - Short-term saccadic adaptation is a mechanism that adjusts saccade amplitude to
      accurately reach an intended saccade target. Short-term saccadic adaptation
      induces a shift of perceived localization of objects flashed before the saccade.
      This shift, being detectable only before an adapted saccade, disappears at some
      time around saccade onset. Up to now, the exact time course of this effect has
      remained unknown. In previous experiments, the mislocalization caused by this
      adaptation-induced shift was overlapping with the mislocalization caused by a
      different, saccade-related localization error, the peri-saccadic compression. Due
      to peri-saccadic compression, objects flashed immediately at saccade onset appear
      compressed towards the saccade target. First, we tested whether the adaptation
      induced shift and the peri-saccadic compression were either independent or
      related processes. We performed experiments with two different luminance-contrast
      conditions to separate the adaptation-induced shift and the peri-saccadic
      compression. Human participants had to indicate the perceived location of briefly
      presented stimuli before, during or after an adapted saccade. Adaptation-induced
      shift occurred similarly in either contrast condition, with or without peri
      saccadic compression. Second, after validating the premise of both processes
      being independent and superimposing, we aimed at characterizing the time course
      of the adaptation-induced shift in more detail. Being present up to 1 s before an
      adapted saccade, the adaptation-induced shift begins to gradually decline from
      about 150 ms before saccade onset, and ceases during the saccade. A final
      experiment revealed that visual references make a major contribution to
      adaptation-induced mislocalization.

PMID- 18716764
TI  - Treadmill locomotion captures visual perception of apparent motion.
AB  - A visual illusion of perceived motion direction induced by treadmill locomotion
      is reported. Directionally ambiguous motions of shifting frames of sinusoidal
      horizontal gratings are perceived moving downward more frequently when the
      stimuli are shown in front of the observers' feet while walking on a treadmill.
      To confirm this effect quantitatively, we asked naive observers to answer whether
      the direction of the motion of the grating pattern was perceived as upward or
      downward while they were walking or standing on a treadmill. The frequency of the
      "downward" response was significantly higher under the walking condition. This
      effect reveals that treadmill locomotion captures perceived direction of
      ambiguous motion in accordance with the direction of the optic flow during
      natural walking. This finding suggests that the effect reflects a perceptual
      mechanism to compensate for the absence of inputs in the action-perception cycle
      during locomotion.

PMID- 18716765
TI  - Missing in action: the effect of obstacle position and size on avoidance while
      reaching.
AB  - When reaching to objects, our hand and arm rarely collide with non-target
      objects, even if our workspace is cluttered. The simplicity of these actions
      hides what must be a relatively sophisticated obstacle avoidance system. Recent
      studies on patients with optic ataxia and visual form agnosia have demonstrated
      that obstacle avoidance is an automatic process, likely governed by the dorsal
      stream (Schindler et al. 2004; Rice et al. 2006). The current study sought to
      quantify how normal participants react to changes in the size and position of non
      target objects in and around their workspace. In the first experiment, 13 right
      handed subjects performed reaches to a target strip in the presence of two non
      target objects, which varied in depth and horizontal configuration. We found that
      objects with horizontal alignments that were asymmetric about midline created
      systematic deviations in reach trajectory away from midline, with participants
      seeming to maximize the distance away from the two objects. These deviations were
      significantly greater for objects nearer in depth and nearly disappeared when the
      objects were placed beyond the target strip. Accompanying this pattern of
      deviation were other significant obstructing effects whereby reaches were
      executed more slowly when objects were close in depth and close to the
      participants reaching (right) hand. In the second experiment, we varied the
      height of the two objects, as well as the depth. Object pairs were now both tall,
      both short, or one-short/one-tall. We replicated the significant depth effects of
      the first experiment, extending the finding to include sensitivity to the size of
      the objects. Here the obstructing effect caused by short objects was similar to
      tall objects when those objects were placed at the depth of the reach target, but
      less than the tall objects when placed at mid-reach. Taken together, these
      experiments suggest that humans possess a sophisticated obstacle avoidance system
      that is extremely sensitive and conservative in evaluating potential obstacles
      and adjusting the reach accordingly.

PMID- 18716766
TI  - Follow-up of intracranial aneurysms treated with detachable coils: comparison of
      3D inflow MRA at 3T and 1.5T and contrast-enhanced MRA at 3T with DSA.
AB  - INTRODUCTION: The purpose of this prospective study was to compare 3T and 1.5T
      magnetic resonance angiography (MRA) with digital subtraction angiography (DSA)
      for the follow-up of endovascular treated intracranial aneurysms to assess the
      grade of occlusion. MATERIALS AND METHODS: Thirty-seven patients with 41
      aneurysms who had undergone endovascular treatment with detachable coils were
      included. MRA was performed on the same day using an eight-channel sensitivity
      encoding head-coil with 3D axial inflow technique. At 3T, a contrast-enhanced
      transverse 3D fast gradient echo acquisition was also performed. Most patients
      underwent DSA the following day. MRA scans and DSA were classified first
      independently by two neuroradiologists and an interventional neuroradiologist.
      Secondly, a consensus was done. Source images, maximum intensity projection,
      multiplanar reconstruction and volume rendering reconstructions were used for MRA
      evaluations. A modification of the Raymond classification, previously used for
      DSA evaluation of recanalization, was used. RESULTS: Statistical comparison of
      the consensus showed that 3T MRA with 3D axial inflow technique had better
      agreement with DSA (kappa = 0.43) than 1.5T MRA(kappa = 0.21) and contrast
      enhanced MRA (CE-MRA) at 3T (kappa = 0.17). The susceptibility artefacts from the
      coil mesh were significally smaller at 3T (p = 0.002-0.007) than at 1.5T.
      CONCLUSION: 3T MRA, using a sensitivity encoding head-coil, showed better
      agreement with DSA than 1.5T and CE-MRA at 3T for evaluation of aneurysms treated
      with endovascular coiling.

PMID- 18716767
TI  - Fetal MR imaging of atelosteogenesis type II (AO-II).
AB  - The diastrophic dysplasia family of osteochondrodysplasias comprises a spectrum
      of skeletal diseases characterized by abnormal growth and remodelling of
      cartilage and bone. They are caused by mutations in the diastrophic dysplasia
      sulfate transporter (DTDST) gene. Different defects in this gene product give
      rise to the variety of phenotypes based on the level of residual transport
      capacity. We reported a case of a fetus with this spectrum, evaluated and
      diagnosed with fetal MRI.

PMID- 18716768
TI  - Cloning and characterization of a novel L-arabinose isomerase from Bacillus
      licheniformis.
AB  - Based on analysis of the genome sequence of Bacillus licheniformis ATCC 14580, an
      isomerase-encoding gene (araA) was proposed as an L-arabinose isomerase (L-AI).
      The identified araA gene was cloned from B. licheniformis and overexpressed in
      Escherichia coli. DNA sequence analysis revealed an open reading frame of 1,422
      bp, capable of encoding a polypeptide of 474 amino acid residues with a
      calculated isoelectric point of pH 4.8 and a molecular mass of 53,500 Da. The
      gene was overexpressed in E. coli, and the protein was purified as an active
      soluble form using Ni-NTA chromatography. The molecular mass of the purified
      enzyme was estimated to be approximately 53 kDa by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and 113 kDa by gel filtration chromatography,
      suggesting that the enzyme is a homodimer. The enzyme required a divalent metal
      ion, either Mn(2+)or Co(2+), for enzymatic activity. The enzyme had an optimal pH
      and temperature of 7.5 and 50 degrees C, respectively, with a k (cat) of 12,455
      min(-1) and a k (cat)/K (m) of 34 min(-1) mM(-1) for L-arabinose, respectively.
      Although L-AIs have been characterized from several other sources, B.
      licheniformis L-AI is distinguished from other L-AIs by its wide pH range, high
      substrate specificity, and catalytic efficiency for L-arabinose, making B.
      licheniformis L-AI the ideal choice for industrial applications, including
      enzymatic synthesis of L-ribulose. This work describes one of the most
      catalytically efficient L-AIs characterized thus far.

PMID- 18716769
TI  - Bacterial CMP-sialic acid synthetases: production, properties, and applications.
AB  - Sialic acids are abundant nine-carbon sugars expressed terminally on
      glycoconjugates of eukaryotic cells and are crucial for a variety of cell
      biological functions such as cell-cell adhesion, intracellular signaling, and in
      regulation of glycoproteins stability. In bacteria, N-acetylneuraminic acid
      (Neu5Ac) polymers are important virulence factors. Cytidine 5'-monophosphate
      (CMP)-N-acetylneuraminic acid synthetase (CSS; EC 2.7.7.43), the key enzyme that
      synthesizes CMP-N-acetylneuraminic acid, the donor molecule for numerous
      sialyltransferase reactions, is present in both prokaryotes and eukaryotic
      systems. Herein, we emphasize the source, function, and biotechnological
      applications of CSS enzymes from bacterial sources. To date, only a few CSS from
      pathogenic bacterial species such as Neisseria meningitidis, Escherichia coli,
      group B streptococci, Haemophilus ducreyi, and Pasteurella hemolytica and an
      enzyme from nonpathogenic bacterium, Clostridium thermocellum, have been
      described. Overall, the enzymes from both Gram-positive and Gram-negative
      bacteria share common catalytic properties such as their dependency on divalent
      cation, temperature and pH profiles, and catalytic mechanisms. The enzymes,
      however, can be categorized as smaller and larger enzymes depending on their
      molecular weight. The larger enzymes in some cases are bifunctional; they have
      exhibited acetylhydrolase activity in addition to their sugar
      nucleotidyltransferase activity. The CSSs are important enzymes for the
      chemoenzymatic synthesis of various sialooligosaccharides of significance in
      biotechnology.

PMID- 18716770
TI  - Construction and characterization of a 9-mer phage display pVIII-library with
      regulated peptide density.
AB  - The construction of a new phagemid vector for display of peptides on the pVIII
      major coat protein of filamentous bacteriophage is described, in which expression
      of pVIII-peptide fusions was placed under the control of the arabinose-inducible
      P(BAD) promoter. The new phagemid showed excellent capacity for the regulation of
      peptide expression, as judged by enzyme-linked immunosorbent assay (ELISA) and
      electron microscopy of immunogold-labeled FLAG peptides displayed on phages.
      Regulation of the density of peptide fusions displayed on phages may offer
      advantages in the search for new peptide ligands due to the possibility of
      regulating the stringency of binding, reducing selection based on avidity effects
      during biopanning. Furthermore, the peptide expression in the absence of inducer
      was effectively shut off, minimizing growth bias of individual clones. A 9-mer
      phage display library prepared using the constructed phagemid was generated by
      insertion of randomly synthesized oligonucleotides close to the N-terminal of the
      pVIII protein. The library comprised a total of 9.4 x 10(9) unique transformants,
      and was confirmed to show high diversity. The functional utility of the library
      was confirmed by the successful affinity selection of peptides binding to matrix
      metalloproteinase-9 (MMP-9). The majority of selected peptides shared the
      consensus motif R(D/N)XXG(M/L)(V/I)XQ, not previously selected during biopanning
      against MMP-9.

PMID- 18716771
TI  - Tn5 transposase-assisted high-efficiency transformation of filamentous fungus
      Phoma herbarum YS4108.
AB  - Conventionally, filamentous fungi are transformed by using conidia or protoplasts
      as recipients. However, induction of sporulation is difficult in some fungi, and
      protoplasting is an awing, frequently frustrating, and batch-dependent work. In
      this study, we established a simple and convenient method to prepare single cells
      from mycelia without enzymatic protoplasting. As a case study on the pathogenic
      fungus Phoma herbarum YS4108, the single cells could be directly and highly
      efficiently transformed with the aid of Tn5 transposase. The optimal electric
      pulse delivery parameters were 25 microF in capacitance, 0.75 kV (0.2-cm cuvette)
      in voltage, and 400 Omega in resistance, under which the efficiency of
      transposase-assisted transformation (TNAT) was enhanced to two to threefold
      compared to that of non-TNAT method, resulting in >230 transformants/cuvette
      (10(6) recipients). Further cell wall weakening of the single cells by lytic
      enzymes and linearization of the plasmid were found to have no effects on
      transformation efficiency, but vector linearization apparently lowered the
      background growth. The present study for the first time explained that Tn5
      transposase could be used to increase transformation efficiency in filamentous
      fungi, and the method presented here may be of wide applicability in different
      studies and may be the first choice when transformation efficiency and
      convenience are priorities and mycelia have to be used as transformation
      recipients.

PMID- 18716772
TI  - Microalgae-based processes for the biodegradation of pretreated piggery
      wastewaters.
AB  - The potential and limitations of photosynthetic oxygenation on carbon and
      nitrogen removal from swine slurry were investigated in batch experiments using
      Chlorella sorokiniana and an acclimated activated sludge as model microorganisms.
      While algal-bacterial systems exhibited similar performance than aerated
      activated sludge in tests supplied with four and eight times diluted slurry, a
      severe inhibition of the biodegradation process was recorded in undiluted and two
      times diluted wastewater. Daily pH adjustment to 7 in enclosed algal-bacterial
      tests at several swine slurry dilutions allowed the treatment of up to two times
      diluted slurries (containing up to 1,180 mg N-NH(4)(+) l(-1)). The combination of
      high pH levels and high NH(4)(+) concentrations was thus identified as the main
      inhibitory factor governing the efficiency of photosynthetically oxygenated
      processes treating swine slurry. Measurements of soluble total organic carbon
      (TOC) and volatile fatty acids (VFA) present in the slurry suggested that VFA
      degradation (mainly acetic and propionic acid) accounted for most of the soluble
      TOC removal, especially during the initial stages of the biodegradation process.
      On the other hand, assimilation into biomass and nitrification to NO(2)(-)
      constituted the main NH(4)(+) removal processes in enclosed algal-bacterial
      systems.

PMID- 18716775
TI  - Diagnostic value of plasma fibronectin level in predicting the presence and
      severity of coronary artery disease.
AB  - The relation between fibronectin and coronary artery disease (CAD) according to
      previous study results is controversial. The aim of the present study is to
      investigate the predictive value of fibronectin in determining the presence and
      severity of CAD. Patients with stable angina (n=62) who had angiographically
      documented CAD, and control patients (n=31) who had normal coronary angiograms,
      were included in the study. Plasma fibronectin levels were determined in all
      patients. Plasma fibronectin level (milligrams per liter) in patients with CAD
      was higher than normal controls (364.2+/-171 vs 265.1+/-135.5, p=0.006). The
      severity of CAD determined according to Gensini score and fibronectin level did
      not show any correlation (r=0.13, p=0.311). If fibronectin level 240 mg/l was
      determined as cutoff, it showed 76% sensitivity, 46% specificity, 46% negative
      predictive value, and 72.3% positive predictive value for predicting CAD. The
      present study showed that plasma fibronectin level in CAD is significantly higher
      than normal control subjects. However, it has no role in predicting the severity
      of CAD.

PMID- 18716773
TI  - Assessment of 18F-labeled mitochondrial complex I inhibitors as PET myocardial
      perfusion imaging agents in rats, rabbits, and primates.
AB  - PURPOSE: Myocardial extractions of mitochondria complex I (MC-I) inhibitors were
      high and well correlated with flow. This study assessed the potential of MC-I
      inhibitors to be developed as myocardial perfusion imaging (MPI) agents. METHODS:
      RP1003, RP1004, and RP1005 representing three classes of MC-I inhibitor were
      synthesized and radio-labeled with (18)F. These agents were evaluated for IC(50)
      values, tissue biodistribution, and cardiac PET imaging. (18)F-RP1004 was further
      examined for first-pass extraction and by imaging in non-human primates (NHP) and
      rats following coronary ligation. RESULTS: RP1003, RP1004, and RP1005 exhibited
      high MC-I inhibitory activity with IC(50) of 3.7, 16.7, and 14.4 nM. Heart
      uptakes in rats (percent injected dose per gram tissue) at 15 and 60 min after
      injection were 3.52 +/- 0.36 and 2.68 +/- 0.20 for (18)F-RP1003, 2.40 +/- 0.21
      and 2.67 +/- 0.27 for (18)F-RP1004, and 2.28 +/- 0.12 and 1.81 +/- 0.17 for (18)F
      RP1005. The heart to lung and liver uptake ratios were favorable for cardiac
      imaging with these agents. In isolated perfused rabbit hearts, the uptake of
      (18)F-RP1004 increased from 0.74 +/- 0.19 to 1.68 +/- 0.39 mL/min/g at flow rates
      of 1.66 to 5.06 mL/min/g. These values were higher than or similar to that of
      (99m)Tc-sestamibi. Cardiac imaging with these agents in rats and rabbits allowed
      visualization of the heart with minimal lung interference and rapid liver
      activity clearance. Imaging with (18)F-RP1004 also showed clear myocardium and
      marked liver activity washout in the NHP and clear detection of the perfusion
      deficit area associated with left coronary artery ligation in the rat.
      CONCLUSION: MC-I inhibitors have the potential to be a new class of MPI agent.

PMID- 18716776
TI  - Vitamin K deficiency amplifies anticoagulation response to ximelagatran: possible
      implications for direct thrombin inhibitors and their clinical safety.
AB  - Dietary vitamin K is known to influence the anticoagulation response to warfarin.
      It is possible that dietary vitamin K availability also influences the
      pharmacological activity of other oral anticoagulants, which target the vitamin-K
      dependent clotting proteins in the coagulation cascade. This study examined
      whether vitamin K insufficiency affected anticoagulation response to the direct
      thrombin inhibitor, ximelagatran. Anticoagulation response to ximelagatran and
      warfarin in rats on a normal diet was compared to those on a vitamin K deficient
      diet. Ximelagatran and warfarin increased prothrombin time (PT) by 1.4- and 1.3
      fold, activated partial thromboplastin time (APTT) by 1.8- and 1.4-fold and
      ecarin clotting time (ECT) by 6.8- and 1.2-fold, respectively, in rats on normal
      diet. Vitamin K deficient diet alone caused modest increases in PT, APTT and ECT.
      The anticoagulant activity of both ximelagatran and warfarin was significantly
      greater in rats on vitamin K deficient diet (6.1- and 12.3-fold for PT, 2.6- and
      5.1-fold for APTT and 2.9- and 1.6-fold for ECT, respectively) compared to those
      on normal diet. Factor II activity was reduced by both ximelagatran (58%) and
      warfarin (44%) in rats on normal diet. However, factor II activity was virtually
      abolished (<0.1%) by both drugs in rats on vitamin K deficient diet. The results
      suggest that oral anticoagulant drugs, whose primary site of action is not within
      the vitamin K cycle, may also exhibit variability in clinical response due to
      dietary variation as the established coumarin drugs such as warfarin.

PMID- 18716778
TI  - Acute hepatic failure following monotherapy with sunitinib for ovarian cancer.

PMID- 18716777
TI  - Phase I dose finding study evaluating the combination of bendamustine with weekly
      paclitaxel in patients with pre-treated metastatic breast cancer: RiTa trial.
AB  - PURPOSE: The aim of the RiTa trial is to establish a feasible combination of
      bendamustine and paclitaxel in a weekly schedule in anthracycline pre-treated
      metastatic breast cancer patients. METHODS: Starting dose of bendamustine was 50
      mg/m(2) and was stepwise increased by 10 mg/m(2) up to 70 mg/m(2). The starting
      dose of paclitaxel was 60 mg/m(2) and was increased up to 90 mg/m(2). There are
      five pre-defined dose levels with three patients per dose level (maximum six
      patients) and six patients in the last dose level according to the Goodman
      design. Dose-limiting toxicities were defined as severe neutropenia and
      thrombocytopenia as well as non-haematological toxicities >/=NCI-CTC grade 3 in
      the first cycle. RESULTS: No dose-limiting toxicity up to 70 mg/m(2) bendamustine
      and 90 mg/m(2) paclitaxel occurred during the first cycle. Over all cycles, the
      following severe haematological toxicities (grade 3 and 4) were documented:
      neutropenia five patients and anaemia one patient. Relevant grade 3 and 4 non
      haematological toxicities over all cycles were fatigue two patients, dyspnoea one
      patient, infection four patients and bone pain in one patient. Five serious
      adverse events, but no therapy related death occurred. Five patients showed a
      complete or partial remission, six patients stable disease and six progressed
      during treatment. The median progression-free survival was 8 months. CONCLUSION:
      Treatment with weekly bendamustine and paclitaxel is a feasible and effective
      regimen in patients with metastatic breast cancer. The recommended dose for
      forthcoming phase II study is 70 mg/m(2) bendamustine and 90 mg/m(2) paclitaxel.

PMID- 18716779
TI  - U3 snoRNA promoter reflects the RNA's function in ribosome biogenesis.
AB  - An efficiently expressed "tagged" gene system was used to study promoter sequence
      elements in genes encoding the U3 snoRNAs of Schizosaccharomyces pombe.
      Transcription was found dependent on two previously thought, mutually exclusive
      elements, a TATA-box, as found in other S. pombe snRNA gene promoters, and a
      Homol D-box, often considered a TATA-box analogue in the promoters of genes that
      encode ribosomal proteins. The Homol D-box is critical while the TATA-box
      strongly influences transcription efficiency but is not essential. The results
      suggest that the U3 snoRNA promoter may represent the fusion of two promoter
      systems reflecting the special role of this RNA in ribosome biogenesis. Steady
      state measurements of cellular RNAs support such a coordinated regulation of the
      U3 snoRNA.

PMID- 18716780
TI  - Causes of death in patients with rheumatoid arthritis autopsied during a 40-year
      period.
AB  - We studied causes of death (CoDs) between 1952 and 1991 assessed by a clinician
      before autopsy and then determined at autopsy by a pathologist in 369 subjects
      with rheumatoid arthritis (RA) and 370 subjects without RA (non-RA). We analysed
      clinical data for RA subjects between 1973 and 1991. In RA subjects, leading
      autopsy-based CoDs were RA, cardiovascular diseases and infections. Between
      diagnoses of CoDs by the clinician and those determined by the pathologist, RA
      subjects had lower agreement than did the non-RA regarding coronary deaths (Kappa
      reliability measure: 0.33 vs. 0.46). In non-RA subjects, autopsy-based coronary
      deaths showed a decline since the 1970s with no such decline in RA. Between
      subjects treated at any time during RA with disease-modifying anti-rheumatic
      drugs and those without, autopsy-based CoDs were similar. Coronary death being
      less accurately diagnosed in RA subjects may indicate that coronary heart disease
      in RA patients often remains unrecognized.

PMID- 18716781
TI  - Giant cell arteritis.
AB  - Giant cell arteritis (GCA) is an immune-mediated chronic vasculitis of large- and
      medium-sized vessels usually occurring in White individuals aged over 50 years,
      in Western countries. The pathological hallmark of GCA is granulomatous
      inflammation of the involved vessels. Headache of new-onset is the most common
      clinical manifestation, and permanent vision loss is the most feared complication
      of GCA. The level of clinical suspicion for GCA should be based upon patient age,
      clinical symptoms, laboratory evaluation, and imaging findings. However, the
      diagnostic gold standard is achieved by histologic confirmation by temporal
      artery biopsy. Corticosteroids remain the only proven treatment for GCA and the
      prognosis for visual recovery is poor.

PMID- 18716782
TI  - A role for natriuretic peptide in lipopolysaccharide-induced fever in Pekin ducks
      (Anas platyrhynchos): is natriuretic peptide an endogenous antipyretic in birds?
AB  - The febrile mechanism in all vertebrates involves endogenous molecules which
      mediate and attenuate the fever response. This mechanism is considered
      phylogenetically conserved, and the molecules are thought to be analogous in
      different species. The above notion is supported by evidence which show avian and
      mammalian fevers to have similar mediators. There is, however, a paucity of
      information regarding the modulators of the avian febrile response. Natriuretic
      peptides were shown to modulate mammalian fevers and, although natriuretic
      peptides are also present in birds, they have never been investigated in the
      context of fever. We induced fever in Pekin ducks with lipopolysaccharide and, at
      the same time, treated the animals with natriuretic peptide antiserum at a dose
      that effectively inhibited the known renal actions of endogenously secreted
      natriuretic peptide. We compared fever responses after ducks received either the
      antiserum or an appropriate control along with the lipopolysaccharide. The
      antiserum did not attenuate the fever responses of ducks. Our results differ from
      the results of a study in rats, which demonstrated natriuretic peptides to be
      potently antipyretic. This molecule seems to be antipyretic in mammals but not in
      ducks. We suggest a species variation regarding the ability of natriuretic
      peptides to modulate fever.

PMID- 18716783
TI  - Case selection in minimally invasive surgical treatment of neuroblastoma.
AB  - PURPOSE: The experience with minimally invasive surgery (MIS) in the treatment of
      neuroblastoma (NB) is anecdotal. The purpose of this study was to evaluate a
      retrospective cohort of NB patients who underwent MIS resection of their primary
      tumors. METHODS: A retrospective study of NB patients who underwent MIS resection
      of their primary tumors over a 3-year period was undertaken. Study outcomes
      included complications, completeness of resection, and event-free and overall
      short-term survival. RESULTS: Of a total of 21 children who underwent surgical
      resection for NB during the period of study, 8 (38%) underwent selected MIS
      resection. Six of the eight (75%) tumors were adrenal in origin and the remainder
      were located in the posterior mediastinum. Distribution by International
      Neuroblastoma Staging System (INSS) stage was: stage 1 (3), stage 2 (2), and
      stage 4 (3). One stage 4 tumor was N-myc amplified. All stage 4 patients
      experienced a >50% tumor volume cytoreduction in response to preoperative
      chemotherapy. All MIS resections were performed without need for blood
      transfusion, or conversion to open procedure, and there were no perioperative
      complications. All eight patients were alive and disease-free at a median 18
      month follow-up. CONCLUSIONS: With appropriate preoperative case selection based
      on anatomic features, MIS tumor resection in patients with NB can be performed
      safely and effectively.

PMID- 18716784
TI  - Lymph node examination as a predictor of long-term outcome in Dukes B colon
      cancer.
AB  - BACKGROUND: Mortality from cancer recurrence in Dukes B patients is approximately
      25-30%. Outcome in Dukes B patients improves in direct relation to the number of
      lymph nodes examined. Examining fewer lymph nodes risks understaging and also
      such patients are less likely to receive chemotherapy. The aim of this study was
      to assess the impact of the number of lymph nodes examined on recurrence and
      mortality in Dukes B colon cancers. MATERIALS AND METHODS: A retrospective
      database was constructed of 328 consecutive patients who underwent resection for
      Dukes B colorectal cancer between January 1993 and December 2001 at Middlemore
      Hospital. Patients with incomplete data, previous colorectal cancer, or
      perioperative deaths were excluded as were cases of rectal cancer. Data for the
      remaining 216 patients was subjected to multivariate and logistic regression
      analysis with 'patient death' or 'cancer recurrence' (CRec5) within 5 years as
      endpoints. A graph was constructed depicting CRec5 as broken down by lymph node
      strata. Receiver operator characteristic (ROC) curves were constructed for
      mortality and CRec5. RESULTS: The mean number of lymph nodes examined was 16.0
      (median 14; range 2-48). The mean number of lymph nodes examined in those who
      died within 5 years was 12.8 vs. 17.5 in those who remained alive (p = 0.0027).
      The mean number of lymph nodes examined in those with evidence of recurrence
      within 5 years was 11.8 vs. 17.1 in those without recurrence (p = 0.0007).
      Analysis at various lymph node strata showed a sharp and statistically
      significant drop in the recurrence rate after the 16th node mark. The ROC curve
      for CRec5 showed that examination of 12 lymph nodes provided maximum sensitivity
      (0.60) and specificity (0.64). CONCLUSION: Examination of more than 16 lymph
      nodes is associated with a significant reduction in cancer recurrence. This
      supports the current clinical practice of harvesting and analysing as many nodes
      as possible during surgical resection and pathological analysis.

PMID- 18716785
TI  - Management of necrotizing pancreatitis in the third trimester of pregnancy.
AB  - INTRODUCTION: Acute pancreatitis during pregnancy is a severe disease with a high
      materno-fetal mortality, which recently decreased because of earlier diagnosis
      and improvement in maternal and neonatal intensive care. CASE: We describe a 19
      year-old woman who presented at 37 weeks gestation with acute abdominal pain and
      attacks of vomiting. Obstetrical and fetal examinations were normal. Biochemical
      investigations and magnetic resonance imaging showed a gallstone migration with
      necrotizing pancreatitis (Balthazar 5 points). Our multidisciplinary team decided
      on nonsurgical conservative treatment including morphine administration and
      enteral feeding, and vaginal delivery which was possible 30 h after induction of
      labor. Follow up was uneventful with a resolution of pain and signs of
      pancreatitis on imaging. CONCLUSION: Magnetic resonance imaging can be useful and
      safe to estimate the severity of acute and necrotizing pancreatitis in the third
      trimester of pregnancy. In case of sterile necrotizing pancreatitis, nonsurgical
      conservative treatment and a vaginal delivery should be performed when possible
      in these patients to reduce the risk of maternal infection.

PMID- 18716786
TI  - Ectopic pregnancy following embolisation of congenital arteriovenous
      malformation.

PMID- 18716787
TI  - Bladder injury during cesarean section.

PMID- 18716788
TI  - Non-puerperal incomplete uterine inversion due to large sub-mucous fundal fibroid
      found at hysterectomy: a report of two cases.
AB  - Two cases of non-puerperal incomplete uterine inversion due to large sub-mucous
      fundal fibroid are presented. This is rare and the diagnosis is often difficult.
      In both the cases diagnosis was made only during surgery.

PMID- 18716789
TI  - CT-based manual segmentation and evaluation of paranasal sinuses.
AB  - Manual segmentation of computed tomography (CT) datasets was performed for robot
      assisted endoscope movement during functional endoscopic sinus surgery (FESS).
      Segmented 3D models are needed for the robots' workspace definition. A total of
      50 preselected CT datasets were each segmented in 150-200 coronal slices with 24
      landmarks being set. Three different colors for segmentation represent diverse
      risk areas. Extension and volumetric measurements were performed. Three
      dimensional reconstruction was generated after segmentation. Manual segmentation
      took 8-10 h for each CT dataset. The mean volumes were: right maxillary sinus
      17.4 cm(3), left side 17.9 cm(3), right frontal sinus 4.2 cm(3), left side 4.0
      cm(3), total frontal sinuses 7.9 cm(3), sphenoid sinus right side 5.3 cm(3), left
      side 5.5 cm(3), total sphenoid sinus volume 11.2 cm(3). Our manually segmented 3D
      models present the patient's individual anatomy with a special focus on
      structures in danger according to the diverse colored risk areas. For safe robot
      assistance, the high-accuracy models represent an average of the population for
      anatomical variations, extension and volumetric measurements. They can be used as
      a database for automatic model-based segmentation. None of the segmentation
      methods so far described provide risk segmentation. The robot's maximum distance
      to the segmented border can be adjusted according to the differently colored
      areas.

PMID- 18716791
TI  - Metabolic and cardiovascular responses during sub-maximal exercise in humans
      after 14 days of head-down tilt bed rest and inactivity.
AB  - VO(2), f (H), Q, SV, [Hb], C(a)O(2), QaO(2), MAP and R (P) were measured in 10
      young subjects at rest and during exercise at 50, 100 and 150 W before and after
      14 days of head-down tilt bed rest (HDTBR) and of ambulatory (AMB) control
      period. f (H) was 18 and 8% higher after HDTBR and AMB, respectively. SV dropped
      by 15% both after HDTBR and AMB, whereas Q did not change. After HDTBR, C(a)O(2)
      decreased at rest (-8%) and at 50 W (-5%), whereas QaO(2) did not change; MAP was
      14 and 6% lower at rest and at 100 W and R (P) decreased by 23% only at rest.
      Changes in f (H) and SV were larger after HDTBR than after AMB. These results
      show that, notwithstanding the drop of SV, moderate-intensity dynamic exercise
      elicited a normal pressure response after 14 days of HDTBR.

PMID- 18716790
TI  - No acute effects of an exposure to 50 ppm acetaldehyde on the upper airways.
AB  - OBJECTIVE: German MAK value of acetaldehyde has been fixed at 50 ppm to prevent
      from irritating effects. The threshold value is mainly based on animal
      experiments. The aim of this study was to evaluate acute effects of an exposure
      to 50 ppm acetaldehyde on the upper airways of human subjects. METHODS: Twenty
      subjects were exposed to 50 ppm acetaldehyde and to air in an exposure chamber
      for 4 h according to a crossover design. Subjective symptoms were assessed by
      questionnaire. Olfactory threshold for n-butanol and mucociliary transport time
      were measured before and after exposure. Concentrations of interleukin 1beta and
      interleukin 8 were determined in nasal secretions taken after exposure. mRNA
      levels of interleukins 1beta, 6 and 8, tumour necrosis factor alpha, granulocyte
      macrophage colony-stimulating factor, monocyte chemotactic protein 1, and
      cyclooxygenases 1 and 2 were measured in nasal epithelial cells, gained after
      exposure. Possible effects were investigated by semiparametric and parametric
      crossover analyses. RESULTS: Exposure to acetaldehyde did not cause any
      subjective irritating symptoms. Olfactory threshold did not change. Mucociliary
      transport time increased insignificantly after exposure to acetaldehyde. Neither
      concentrations of interleukins in nasal secretions nor mRNA levels of
      inflammatory factors were higher after exposure to acetaldehyde. CONCLUSION: An
      acute exposure to 50 ppm acetaldehyde did not cause any adverse effects in test
      subjects.

PMID- 18716792
TI  - Minimally invasive thyroid and parathyroid surgery is not a question of length of
      the incision.
AB  - INTRODUCTION: Postoperative cosmesis in the neck is often a major concern of
      patients, particularly women, undergoing thyroid or parathyroid surgery.
      Therefore, a reduction in the length of the cervical incision, and even more so,
      having no scar in the neck, is particularly appealing to these patients. Over the
      last years, many different so-called minimally invasive procedures have been
      proposed for the treatment of thyroid and parathyroid diseases, the primary aim
      being to improve the cosmetic results. Nevertheless, the concept of surgical
      invasiveness cannot be limited to the length or to the site of the skin incision.
      It must be extended to all structures dissected during the procedure. Therefore,
      minimally invasive thyroidectomy or minimally invasive parathyroidectomy should
      properly be defined as operations through a short, less than 3 cm, and discrete
      incision that permits direct access to the thyroid or parathyroid gland,
      resulting in a focused dissection. In addition, type of anesthesia, duration of
      the operation, postoperative pain, complication and success rates, and long-term
      outcome should also be taken into account to assess surgical invasiveness.
      CONCLUSION: Thyroid and parathyroid operations that minimize the incision but
      keep it in the neck may be considered minimally invasive not only in respect of
      the size of the skin incision but also, and above all, in respect of the
      accessibility of the operative field and extent of dissection. These operations
      have some advantages over conventional cervicotomy in terms of postoperative pain
      and cosmetic results. Until now, there is no evidence to state that morbidity of
      these new approaches is at least equal to the conventional equivalent. Operations
      that employ an extracervical approach, which have the advantage of leaving no
      scar in the neck, cannot reasonably be described as minimally invasive, as they
      require more dissection than conventional open surgery.

PMID- 18716793
TI  - Cultured ruminal epithelial cells express a large-conductance channel permeable
      to chloride, bicarbonate, and acetate.
AB  - The absorption of short-chain fatty acids (SCFA) from the rumen requires
      efficient mechanisms for both apical uptake and basolateral extrusion. Previous
      studies suggest that the rumen expresses a basolateral chloride conductance that
      might be permeable to SCFA. In order to characterize this conductance in more
      detail, isolated cultured ruminal epithelial cells were studied with the patch
      clamp technique, revealing a whole-cell conductance with p(Cl(-)) approximately
      p(NO(3) (-)) > p(HCO(3) (-)) > p(acetate(-)) > p(gluconate(-)). Currents could be
      blocked by diisothiocyanato-stilbene-2,2'-disulfonic acid (1 mmol l(-1) > 100
      micromol l(-1)), 5-nitro-2-(3-phenylpropyl-amino)benzoic acid (50 micromol l(
      1)), niflumic acid (100 micromol l(-1)), and p-chloromercuribenzoate (1 mmol l(
      1)). Single-channel conductance was 350 +/- 7 pS for chloride and 142 +/- 7 pS
      for acetate. Open probability could be fitted with a three-state gating model. We
      propose a role for this channel in mediating the permeation of chloride,
      bicarbonate, and acetate across the basolateral membrane of the ruminal
      epithelium.

PMID- 18716794
TI  - Cloning and characterisation of a maize carotenoid cleavage dioxygenase (ZmCCD1)
      and its involvement in the biosynthesis of apocarotenoids with various roles in
      mutualistic and parasitic interactions.
AB  - Colonisation of maize roots by arbuscular mycorrhizal (AM) fungi leads to the
      accumulation of apocarotenoids (cyclohexenone and mycorradicin derivatives).
      Other root apocarotenoids (strigolactones) are involved in signalling during
      early steps of the AM symbiosis but also in stimulation of germination of
      parasitic plant seeds. Both apocarotenoid classes are predicted to originate from
      cleavage of a carotenoid substrate by a carotenoid cleavage dioxygenase (CCD),
      but the precursors and cleavage enzymes are unknown. A Zea mays CCD (ZmCCD1) was
      cloned by RT-PCR and characterised by expression in carotenoid accumulating E.
      coli strains and analysis of cleavage products using GC-MS. ZmCCD1 efficiently
      cleaves carotenoids at the 9, 10 position and displays 78% amino acid identity to
      Arabidopsis thaliana CCD1 having similar properties. ZmCCD1 transcript levels
      were shown to be elevated upon root colonisation by AM fungi. Mycorrhization led
      to a decrease in seed germination of the parasitic plant Striga hermonthica as
      examined in a bioassay. ZmCCD1 is proposed to be involved in cyclohexenone and
      mycorradicin formation in mycorrhizal maize roots but not in strigolactone
      formation.

PMID- 18716795
TI  - Nerve growth factor/nuclear factor-kappaB pathway as a therapeutic target in
      breast cancer.
AB  - INTRODUCTION: Nuclear factor-kappaB pathway (NF-kappaB) is activated in many
      breast cancers. NF-small kappaB has interactions with other pathways such as the
      nerve growth factor (NGF) pathway, which is involved in the survival and
      proliferation of breast cancer cells. NGF treatment of breast cancer cells
      activates NF-kappaB resulting in the inhibition of ceramide-induced apoptosis.
      NGF effects on apoptosis and cell proliferation are mediated through p75NTR and
      p140TrkA receptors, respectively. In this study we investigate the NGF/NF-kappaB
      pathway as a therapeutic target in breast cancer. RESULTS: We demonstrate that
      p75NTR inhibitor Pep5, p140TrkA inhibitor K-252a, and NF-kappaB inhibitor BAY11
      7085 have pro-apoptotic and anti-proliferation activities in breast cancer cells.
      We also show a synergy in combining the NGF receptor inhibitors with the
      conventional breast cancer treatments tamoxifen and taxol. CONCLUSION: These data
      suggest that NGF/NF-kappaB pathway is a potential therapeutic target in breast
      cancer.

PMID- 18716796
TI  - Alteration of the expression profiles of acidic mucin, sialytransferase, and
      sulfotransferases in the intestinal epithelium of rats infected with the nematode
      Nippostrongylus brasiliensis.
AB  - Acidic mucins such as sialomucin and sulfomucin produced by intestinal epithelial
      cells have been implicated in the protection of the mucosa from pathogens. In the
      present study, we analyzed the alteration of acidic mucins in the jejunum of
      euthymic and athymic rats infected with the nematode Nippostrongylus brasiliensis
      using alcian blue staining and a high iron-diamine method. The numbers of
      sialomucin+ goblet cells increased markedly 7 and 10 days post-infection and
      decreased gradually thereafter in euthymic rats, while athymic rats did not show
      sialomucin+ goblet cell hyperplasia at least until 28 days post-infection,
      suggesting that sialomucin production might be regulated by thymus-derived T
      cells. On the other hand, the numbers of sulfomucin+ goblet cells increased
      markedly 28 days post-infection in both euthymic and athymic rats despite the
      fact that sulfomucin+ goblet cell numbers in uninfected athymic rats were
      significantly smaller than in euthymic rats. Real-time polymerase chain reaction
      studies on the gene transcription levels of O-glycan sulfotransferases Gal3ST1,
      Gal3ST2, Gal3ST3, and Gal3ST4 in the jejunal epithelium increased gradually
      toward day 28 post-infection in euthymic and athymic rats. These results suggest
      that the production of sulfomucin and expression of Gal3STs are inducible by
      nematode infection without the activation of thymus-derived T cells.

PMID- 18716797
TI  - The Lawc protein is required for proper transcription by RNA polymerase II in
      Drosophila.
AB  - Genetic analysis of the Drosophila leg-arista-wing complex (lawc) gene suggests a
      role for the Lawc protein in chromatin-related processes based on its
      classification as a trxG gene but the molecular mechanisms of its function remain
      elusive. We have found that Lawc is a small, cysteine-rich protein that is
      present in most of the interbands of polytene chromosomes. In agreement with this
      observation, Lawc co-localizes with RNA polymerase IIo (Pol IIo) and it is
      recruited to transcribed loci after elongation by Pol IIo has begun. Lawc
      interacts with the nuclear proteasome regulator dREGgamma in a yeast two-hybrid
      assay and both proteins co-localize on polytene chromosomes. In addition, a
      mutation in lawc interacts genetically with a mutation in a component of the
      proteasome. lawc mutants show decreased expression of some genes, while the
      levels of Pol IIoSer2 increase. We conclude that Lawc is required for proper
      transcription by RNA polymerase II in a process that involves the nuclear
      proteasome.

PMID- 18716798
TI  - Association of Interleukin-1 gene polymorphisms with central obesity and
      metabolic syndrome in a coronary heart disease population.
AB  - The objective of this study was to determine whether single nucleotide
      polymorphisms (SNPs) in the Interleukin-1 (IL-1) gene family are associated with
      central obesity and metabolic syndrome in a coronary heart disease population.
      The IL-1 alpha C-889T (rs1800587) and IL-1 beta +3954 (rs1143634) SNPs were
      studied in a Western Australian coronary heart disease (CHD) population (N =
      556). Subjects who were TT homozygous at either SNP had larger waist
      circumference (IL-1 alpha: 1.8 cm greater, P = 0.04; IL-1 beta: 4 cm greater, P =
      0.0004) compared with major allele homozygotes. Individuals with two copies of
      the IL-1 alpha:IL-1 beta T:T haplotype had greater waist circumference (4.7 cm
      greater, P = 0.0001) compared to other haplotypes. There was a significant
      interaction between the IL-1 beta SNP and BMI level on waist circumference (P =
      0.01). When the cohort was stratified by median BMI, TT carriers for IL-1 beta
      with above median BMI had greater waist circumference (6.1 cm greater, P = 0.007)
      compared to baseline carriers, whilst no significant association was seen in the
      below median group. Similarly, when the cohort was stratified by median
      fibrinogen level (IL-1 alpha interaction P = 0.01; IL-1 beta interaction P =
      0.04), TT carriers for both SNPs in the above median fibrinogen group had greater
      waist circumference (IL-1 alpha 2.7 cm greater, P = 0.007; IL-1 beta 3.3 cm
      greater, P = 0.003) compared with major allele homozygotes. This association was
      not seen in the below median group. Also, we found a trend of increased metabolic
      syndrome for IL-1 beta TT homozygotes (P = 0.07). In conclusion, our findings
      suggest that in a CHD population IL-1 gene polymorphisms may be involved in
      increased central obesity, and the genetic influences are more evident among
      patients who have a higher level of obesity or inflammatory markers.

PMID- 18716799
TI  - Transgenerational effects of global environmental change: long-term CO(2) and
      nitrogen treatments influence offspring growth response to elevated CO(2).
AB  - Global environmental changes can have immediate impacts on plant growth,
      physiology, and phenology. Long-term effects that are only observable after one
      or more generations are also likely to occur. These transgenerational effects can
      result either from maternal environmental effects or from evolutionary responses
      to novel selection pressures and are important because they may alter the
      ultimate ecological impact of the environmental change. Here, we show that
      transgenerational effects of atmospheric carbon dioxide (CO(2)) and soil nitrogen
      (N) treatments influence the magnitude of plant growth responses to elevated
      CO(2) (eCO(2)). We collected seeds from Lupinus perennis, Poa pratensis, and
      Schizachyrium scoparium populations that had experienced five growing seasons of
      ambient CO(2) (aCO(2)) or eCO(2) treatments and ambient or increased N deposition
      and planted these seeds into aCO(2) or eCO(2) environments. We found that the
      offspring eCO(2) treatments stimulated immediate increases in L. perennis and P.
      pratensis growth and that the maternal CO(2) environment influenced the magnitude
      of this growth response for L. perennis: biomass responses of offspring from the
      eCO(2) maternal treatments were only 54% that of the offspring from the aCO(2)
      maternal treatments. Similar trends were observed for P. pratensis and S.
      scoparium. We detected some evidence that long-term N treatments also altered
      growth responses to eCO(2); offspring reared from seed from maternal N-addition
      treatments tended to show greater positive growth responses to eCO(2) than
      offspring from ambient N maternal treatments. However, the effects of long-term N
      treatments on offspring survival showed the opposite pattern. Combined, our
      results suggest that transgenerational effects of eCO(2) and N-addition may
      influence the growth stimulation effects of eCO(2), potentially altering the long
      term impacts of eCO(2) on plant populations.

PMID- 18716800
TI  - Clinical and microbiological effects of an essential-oil-containing mouth rinse
      applied in the "one-stage full-mouth disinfection" protocol--a randomized doubled
      blinded preliminary study.
AB  - The aim of this randomized double-blinded preliminary study was to evaluate the
      clinical and microbiological long-term effects of an essential-oil-containing
      mouth rinse as the active agent utilized in the "one-stage full-mouth
      disinfection protocol." Probing pocket depth and plaque and gingival indices were
      evaluated by the same calibrated examiner in all teeth of 20 moderate chronic
      periodontitis subjects. Presence of Aggregatibacter actinomycetemcomitans,
      Porphyromonas gingivalis, and Tannerella forsythensis were determined by
      polymerase chain reaction in nonstimulated saliva, tongue dorsum, and pooled
      subgingival samples. The subjects were randomized into two groups: full-mouth
      disinfection plus essential oils (Listerine) or full-mouth disinfection plus
      placebo. Clinical and microbial parameters were evaluated at baseline (T0), 45
      (T1) and 180 (T2) days after therapy and analyzed using analysis of variance,
      Student t, and Wilcoxon tests (p < 0.05). No significant differences were
      observed between groups regarding clinical measurements at baseline. However, in
      the later examinations, T1 and T2, the test group always presented higher
      reductions of pocket depth, plaque index, and gingival index compared to the
      control group. The essential-oils group revealed significant reduction on
      occurrence of P. gingivalis in saliva comparing baseline and 45 days; this
      difference still remain at 180 days. The essential-oil-containing mouth rinse
      demonstrated beneficial effects on clinical parameters. Microbiological findings
      were less consistent. The results of this preliminary study suggest further
      investigations.

PMID- 18716801
TI  - The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the
      Chinese population.
AB  - The c.G4883C variant in the leucine-rich repeat kinase 2 (LRRK2) gene (protein
      effect: Arg1628Pro) has been recently proposed as a second risk factor for
      sporadic Parkinson's disease in the Han Chinese population (after the Gly2385Arg
      variant). In this paper, we analyze the Arg1628Pro variant and the associated
      haplotype in a large sample of 1,337 Han subjects (834 patients and 543 controls)
      ascertained from a single referral center in Taiwan. In our sample, the
      Arg1628Pro allele was more frequent among patients (3.8%) than among controls
      (1.8%; p = 0.004, OR 2.13, 95% CI 1.29-3.52). Sixty heterozygous and two
      homozygous carriers of the Arg1628Pro variant were identified among the patients,
      of which only one was also a carrier of the LRRK2 Gly2385Arg variant. We also
      show that carriers of the Arg1628Pro variant share a common, extended haplotype,
      suggesting a founder effect. Parkinson's disease onset age was similar in
      patients who carried the Arg1628Pro variant and in those who did not carry it.
      Our data support the contention that the Arg1628Pro variant is a second risk
      factor for Parkinson's disease in the Han Chinese population. Adding the
      estimated effects of Arg1628Pro (population attributable risk [PAR] approximately
      4%) and Gly2385Arg variants (PAR approximately 6%) yields a total PAR of
      approximately 10%.

PMID- 18716802
TI  - Social attention in keas, dogs, and human children.
AB  - Understanding animals' abilities to cooperate with and learn from each other has
      been an active field of research in recent years. One important basis for all
      types of social interactions is the disposition of animals to pay attention to
      each other-a factor often neglected in discussions and experiments. Since
      attention differs between species as well as between individuals, it is likely to
      influence the amount and type of information different species and/or observers
      may extract from conspecifics in any given situation. Here, we carried out a
      standardized comparative study on attention towards a model demonstrating food
      related behavior in keas, dogs and children. In a series of experimental
      sessions, individuals watched different conspecific models while searching,
      manipulating and feeding. Visual access to the demonstration was provided by two
      observation holes, which allowed us to determine exactly how often and for how
      long observers watched the model. We found profound differences in the factors
      that influence attention within as well as between the tested species. This study
      suggests that attention should be incorporated as an important variable when
      testing species in social situations.

PMID- 18716803
TI  - A foodborne outbreak of a group A streptococcal infection in a Japanese
      university hospital.
AB  - We describe an outbreak of foodborne tonsillopharyngitis caused by group A
      streptococcus (GAS), a rarely reported event that occurred during a campus
      orientation meeting in Japan. Of 461 students and staff members who had eaten
      boxed lunches during a meeting at Kitasato University, 298 developed sore throat
      and/or fever, and 285 underwent medical examination. Amoxicillin was prescribed
      when throat culture specimens yielded GAS. The attack rate was 64.6%. T-25 GAS
      was isolated from 150 examined persons. Of 65 patients who received amoxicillin
      for 3 days, GAS was eradicated before the first follow-up throat culture in 46
      (70.8%) cases. Susceptibility was demonstrated to penicillins, cephalosporins,
      and macrolides in 86 GAS isolates obtained more than once from a given patient.
      GAS strains isolated at various time points were indistinguishable by pulsed
      field gel electrophoresis (PFGE), and prtF1 was present. GAS strains were often
      difficult to eradicate because of a short initial treatment period, patient
      compliance problems, and the presence of prtF1.

PMID- 18716804
TI  - Role of spiramycin/cotrimoxazole association in the mother-to-child transmission
      of toxoplasmosis infection in pregnancy.
AB  - The purpose of this report is to evaluate the efficacy and safety of
      spiramycin/cotrimoxazole in the mother-to-child transmission of Toxoplasma gondii
      infection. We retrospectively analysed 76 infants born to mothers with
      toxoplasmosis during pregnancy and estimated the risk of mother-to-child
      transmission considering the gestational age at the time of infection. Seventy
      six mothers were given spiramycin, cotrimoxazole and folinic acid; only two
      babies (2.6%) were infected by Toxoplasma and none of them showed signs or
      symptoms of congenital infection or interference of sulphamid on tetrahydrofolate
      reductase (THFR) either at birth or during follow-up. Treatment did not need to
      be stopped in any mother because of adverse drug effects. Our results seem to
      encourage the use of spiramycin/cotrimoxazole in women with toxoplasmosis during
      pregnancy.

PMID- 18716805
TI  - Nationwide surveillance of antimicrobial resistance among Enterobacteriaceae in
      intensive care units in Taiwan.
AB  - To determine the antimicrobial resistance profiles among clinical isolates of
      Enterobacteriaceae in Taiwanese intensive care units (ICUs), a national
      surveillance of antibiotic resistance among important Enterobacteriaceae was
      conducted from September 2005 through November 2005 at the ICUs of ten major
      teaching hospitals in Taiwan. A total of 574 Enterobacteriaceae isolates
      recovered from various clinical samples of our ICU patients were submitted for in
      vitro test. Minimum inhibitory concentrations (MICs) of these isolates to 18
      antimicrobial agents were determined by the broth microdilution method. The
      prevalences of Enterobacteriaceae isolates with phenotypic extended-spectrum beta
      lactamase (ESBL) production were 26% in Klebsiella pneumoniae, 16% in Serratia
      marcescens, 14% in Escherichia coli, and 13% in Proteus mirabilis, in which a
      significantly rising prevalence of ESBL production among K. pneumoniae was noted
      (p = 0.002) when compared with a previous Taiwanese survey in 2000. Heterogeneous
      resistance to various fluoroquinolones was found among our Enterobacteriaceae
      isolates, except for Enterobacter cloacae. Emergence of ertapenem-resistant
      isolates of E. coli, K. pneumoniae, E. cloacae, and S. marcescens was noted.
      Gradually increasing rates of drug-resistant Enterobacteriaceae were noted in
      Taiwanese ICUs. Periodic surveillance of the evolutionary trend of antimicrobial
      resistance among ICU isolates is crucial for starting appropriately empirical
      antimicrobial therapy in the future.

PMID- 18716806
TI  - Simultaneous species identification and detection of rifampicin resistance in
      staphylococci by sequencing of the rpoB gene.
AB  - In recent years, coagulase-negative staphylococci (CoNS) have been increasingly
      recognised as causative agents of various infections, especially in
      immunocompromised patients and related to implanted foreign body materials. In
      this study, rpoB sequencing was used for simultaneous species identification and
      detection of rifampicin resistance in clinical staphylococci isolates. Forty-nine
      (96%) out of 51 isolates, representing 17 different Staphylococcus species
      according to the initial phenotypic species identification, were identified to
      the species level using rpoB sequencing. Furthermore, the two remaining isolates
      were Kocuria sp. and Corynebacterium sp. respectively, according to 16S rRNA
      sequencing. Comparison with the phenotypic diagnostics also revealed that 8 (16%)
      of the 49 isolates differed regarding identified species. Discrepant analysis
      confirmed the result of the rpoB sequencing for all except 2 of these isolates,
      which could not be distinguished as single species using 16S rRNA sequencing.
      Regarding detection of rifampicin resistance, isolates obtained pre- and post
      treatment with rifampicin were examined. These isolates comprised S. aureus (7
      patients) and S. lugdunensis (1 patient). Rifampicin resistance was mainly
      detected following short-term treatment with rifampicin in combination with
      isoxazolyl-penicillin, or long-term treatment with rifampicin and ciprofloxacin.
      Each rifampicin-resistant isolate displayed an identical rpoB sequence as their
      corresponding rifampicin-susceptible isolates except for one (n = 6) or two (n =
      1) nonsynonymous single nucleotide polymorphisms, or insertion of one codon (n =
      1). In conclusion, rpoB sequencing is a rapid, objective and accurate method of
      species identification and simultaneous detection of rifampicin resistance in
      staphylococci.

PMID- 18716807
TI  - Genetic characterization of the UCS and Kex1 loci of Pneumocystis jirovecii.
AB  - Nucleotide variation in the Pneumocystis jirovecii upstream conserved sequence
      (UCS) and kexin-like serine protease (Kex1) loci was studied in pulmonary
      specimens from Portuguese HIV-positive patients. DNA was extracted and used for
      specific molecular sequence analysis. The number of UCS tandem repeats detected
      in 13 successfully sequenced isolates ranged from three (9 isolates, 69%) to four
      (4 isolates, 31%). A novel tandem repeat pattern and two novel polymorphisms were
      detected in the UCS region. For the Kex1 gene, the wild-type (24 isolates, 86%)
      was the most frequent sequence detected among the 28 sequenced isolates.
      Nevertheless, a nonsynonymous (1 isolate, 3%) and three synonymous (3 isolates,
      11%) polymorphisms were detected and are described here for the first time.

PMID- 18716808
TI  - Susceptibility of common aerobic pathogens to tigecycline: results of a
      surveillance study in Germany.
AB  - Tigecycline is a novel antimicrobial agent for parenteral use encompassing a
      broad spectrum of bacterial pathogens, including multi-resistant organisms. Here,
      we report the results of the first nationwide surveillance trial that was
      conducted in order to evaluate the susceptibility of bacterial isolates to
      tigecycline in a European country prior to its clinical use. A total of 2,610
      Gram-positive and Gram-negative organisms recovered from hospitalized patients
      were tested. Minimum inhibitory concentrations (MICs) were determined using the
      microdilution method. All enterococci, staphylococci (including methicillin
      resistant Staphylococcus aureus; MRSA), and streptococci tested were tigecycline
      susceptible, except one isolate of Staphylococcus haemolyticus. Among the Gram
      negative bacteria, 100% of the Escherichia coli isolates (including extended
      spectrum beta-lactamase [ESBL]-producers) were tigecycline-susceptible, while
      about 10% of the Enterobacter cloacae and Klebsiella pneumoniae isolates were
      resistant. Based on the results of this surveillance study, tigecycline may
      represent a suitable option most notably for the empiric treatment of bacterial
      mixed infections, including in clinical situations in which multi-resistant
      organisms are suspected.

PMID- 18716809
TI  - Mannosylerythritol lipids: a review.
AB  - Mannosylerythritol lipids (MELs) are surface active compounds that belong to the
      glycolipid class of biosurfactants (BSs). MELs are produced by Pseudozyma sp. as
      a major component while Ustilago sp. produces them as a minor component. Although
      MELs have been known for over five decades, they recently regained attention due
      to their environmental compatibility, mild production conditions, structural
      diversity, self-assembling properties and versatile biochemical functions. In
      this review, the MEL producing microorganisms, the production conditions, their
      applications, their diverse structures and self-assembling properties are
      discussed. The biosynthetic pathways and the regulatory mechanisms involved in
      the production of MEL are also explained here.

PMID- 18716810
TI  - Effect of growth substrate, method of fermentation, and nitrogen source on
      lignocellulose-degrading enzymes production by white-rot basidiomycetes.
AB  - The exploration of seven physiologically different white rot fungi potential to
      produce cellulase, xylanase, laccase, and manganese peroxidase (MnP) showed that
      the enzyme yield and their ratio in enzyme preparations significantly depends on
      the fungus species, lignocellulosic growth substrate, and cultivation method. The
      fruit residues were appropriate growth substrates for the production of
      hydrolytic enzymes and laccase. The highest endoglucanase (111 U ml(-1)) and
      xylanase (135 U ml(-1)) activities were revealed in submerged fermentation (SF)
      of banana peels by Pycnoporus coccineus. In the same cultivation conditions
      Cerrena maxima accumulated the highest level of laccase activity (7,620 U l(-1)).
      The lignified materials (wheat straw and tree leaves) appeared to be appropriate
      for the MnP secretion by majority basidiomycetes. With few exceptions, SF favored
      to hydrolases and laccase production by fungi tested whereas SSF was appropriate
      for the MnP accumulation. Thus, the Coriolopsis polyzona hydrolases activity
      increased more than threefold, while laccase yield increased 15-fold when tree
      leaves were undergone to SF instead SSF. The supplementation of nitrogen to the
      control medium seemed to have a negative effect on all enzyme production in SSF
      of wheat straw and tree leaves by Pleurotus ostreatus. In SF peptone and ammonium
      containing salts significantly increased C. polyzona and Trametes versicolor
      hydrolases and laccase yields. However, in most cases the supplementation of
      media with additional nitrogen lowered the fungi specific enzyme activities.
      Especially strong repression of T. versicolor MnP production was revealed.

PMID- 18716811
TI  - Pollution control in pulp and paper industrial effluents using integrated
      chemical-biological treatment sequences.
AB  - The main objective of the present study was to improve the quality of pulp and
      paper industrial wastewater of two local mills RAKTA and El-Ahlia, Alexandria,
      Egypt, and to bring their pollutant contents to safe discharge levels. Quality
      improvement was carried out using integrated chemical and biological treatment
      approaches after their optimization. Chemical treatment (alum, lime, and ferric
      chloride) was followed by oxidation using hydrogen peroxide and finally
      biological treatment using activated sludge (90 min for RAKTA and 60 min for El
      Ahlia effluents). Chemical coagulation produced low-quality effluents, while pH
      adjustment during coagulation treatment did not enhance the quality of the
      effluents. Maximum removal of the tested pollutants was achieved using the
      integrated treatment and the pollutants recorded residual concentrations (RCs) of
      34.67, 17.33, 0.13, and 0.43 mg/l and 15.0, 11.0, 0.0, and 0.13 mg/l for chemical
      oxygen demand (COD), biochemical oxygen demand (BOD5), tannin and lignin, and
      silica in RAKTA and El-Ahlia effluents, respectively, all of which were below
      their maximum permissible limits (MPLs) for the safe discharge into water
      courses. Specific oxygen uptake rate (SOUR) and sludge volume index (SVI) values
      reflect good conditions and healthy activated sludge. Based on the previous
      results, optimized conditions were applied as bench scale on the raw effluents of
      RAKTA and El-Ahlia via the batch chemical and the biological treatment sequences
      proposed. For RAKTA effluents, the sequence was as follows: (1) coagulation with
      375 mg/l FeCl3, (2) oxidation with 50 mg/l hydrogen peroxide, and (3) biological
      treatment using activated sludge with 2,000 mg/l initial concentration and 90 min
      hydraulic retention time (HRT), while for El-Ahlia raw effluents, the sequence
      was (1) coagulation with 250 mg/l FeCl3, (2) oxidation with 45 mg/l hydrogen
      peroxide, and (3) biological treatment using activated sludge with 2,000 mg/l
      initial concentration and 60 min HRT. In conclusion, results confirmed that the
      application of the proposed sequential treatments removed almost all COD, BOD5,
      high molecular weight compounds, and silica from RAKTA and El-Ahlia influents and
      produced high-quality effluents, thus achieving the main objective of this study.

PMID- 18716812
TI  - Nutrient broth/PEG200/TritonX114/Tween80/Chloroform microemulsion as a reservoir
      of solubilized sitosterol for biotransformation to androstenedione.
AB  - Microemulsions (ME) can act as a reservoir of solubilized hydrophobic substrates.
      The biotransformation of hydrophobic sitosterol to androstenedione (AD) with MEs
      prepared from nutrient broth and PEG 200 (1:1) as aqueous phase, 40 g/l
      sitosterol dissolved in chloroform as organic phase, Triton X114 and Tween 80
      (1:1) as surfactant phase, was investigated. The phase behavior of this system
      was studied for ten different ratios(w/w), 10:0, 9:1, 8:2, 7:3, 6:4, 5:5, 4:6,
      3:7, 2:8, 1:9 and 0:10 of the organic phase and surfactant at 30 degrees C. A
      pseudoternary phase diagram was constructed to demarcate the region giving stable
      MEs. The maximum solubility of sitosterol in ME medium was observed to be 8 g/l,
      which is 3 orders of magnitude higher than the reported sitosterol solubility of
      2-4 mg/l in aqueous medium. The ME medium was used for biotransformation studies
      and a comparative result has been reported. Transmission electron microscopy of
      cells grown in ME having oil, surfactant and aqueous phase in the ratio of
      6:14:80 showed a weakened cell wall structure that permitted production of 465.86
      mg/l AD.

PMID- 18716813
TI  - Effect of ionic liquid [BMIM][PF6] on asymmetric reduction of ethyl 2-oxo-4
      phenylbutyrate by Saccharomyces cerevisiae.
AB  - The effect of ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate
      ([BMIM][PF6]) on the asymmetric reduction of ethyl 2-oxo-4-phenylbutyrate (EOPB)
      to synthesize optical active ethyl 2-hydroxy-4-phenylbutyrate (EHPB) catalyzed by
      Saccharomyces cerevisiae was investigated. (R)-EHPB [70.4%, e.e.(R)] is obtained
      using ethyl ether or benzene as the solvent. The main product is (S)-EHPB [27.7%,
      e.e.(S)] in [BMIM][PF6]. However, in ionic liquid-water (10:1, v/v) biphasic
      system, the enantioselectivity of the reduction is shifted towards (R)-side, and
      e.e.(R) is increased from 6.6 to 82.5% with the addition of ethanol (1%, v/v).
      The effect of the use of [BMIM][PF6] as an additive in relatively small amounts
      on the reduction was also studied. We find that there is a decline in the
      enantioselectivity of the reduction in benzene. In addition, a decrease in the
      conversion of EOPB and the yield of EHPB with increasing [BMIM][PF6]
      concentrations occurs in either organic solvent-water biphasic systems or
      benzene.

PMID- 18716814
TI  - Enhanced biotransformation of sitosterol to androstenedione by Mycobacterium sp.
      using cell wall permeabilizing antibiotics.
AB  - Mycobacterial cell wall is rigid and offers a high resistance to the transport of
      sitosterol into cytosol. The effect of ethambutol, penicillin, polymixin and
      bacitracin on biotransformation of sitosterol to androstenedione by modification
      of cell wall permeability was examined. Drug sensitivity assay results
      established that bacitracin increased the permeability of the cell wall to
      hydrophobic compounds. Growth inhibitory study of bacitracin and rifamycin,
      individually as well as in combination showed that these two antibiotics act
      synergistically to reduce cell growth. A comparison of transmission electron
      micrograph results of the bacitracin-treated cells with untreated cells, revealed
      deformities caused in the cell wall structure by bacitracin treatment. These
      deformities increased the cell wall permeability and transport of sitosterol
      inside the cell, and thus enhanced androstenedione (AD) production. A maximum of
      1.37, 1.44, 1.65 and 1.76 g AD per gram dry cell weight of mycobacterial cells
      was produced in the presence of ethambutol, penicillin, polymixin and bacitracin,
      respectively. Below the minimum inhibitory concentration, bacitracin can be used
      as potent enhancer of permeability of hydrophobic substances across the
      mycobacterial cell wall.

PMID- 18716815
TI  - Silent echo-planar imaging for auditory FMRI.
AB  - INTRODUCTION: The effect of the acoustic scanner noise produced by gradient coil
      switching on the auditory evoked BOLD signal represents a well-known problem in
      auditory functional MRI (FMRI). In this paper, a new low-noise echo-planar
      imaging (EPI) sequence is presented that is optimized for auditory FMRI
      measurements. METHODS: The sequence produces a narrow-band acoustic frequency
      spectrum by using a sinusoidal readout echo train and a constant phase encoding
      gradient. This narrow band is adapted to the frequency response function of the
      MR scanner by varying the switching frequency of the sinusoidal readout gradient.
      RESULTS: Compared to a manufacturer-provided standard EPI sequence, the acoustic
      noise reduction amounts to up to 20 dBA. Using a simple block design paradigm
      contrasting presentation of a pure tone during ON blocks and "silence" (absence
      of the tone) during OFF blocks, the new low-noise sequence was evaluated and
      compared to the standard EPI sequence. Statistical parametric mapping (SPM)
      resulted in higher levels of significance of auditory activation for the low
      noise sequence. DISCUSSION: These findings strongly suggest that the low-noise
      sequence may generate enhanced BOLD contrasts compared to the standard EPI
      sequences commonly used in FMRI.

PMID- 18716816
TI  - Characterization of the toxic effects of cadmium and 3.5-dichlorophenol on
      nitrifying activity and mortality in biologically activated sludge systems-effect
      of low temperature.
AB  - BACKGROUND, AIMS, AND SCOPE: Sometimes, urban wastewaters convey a more or less
      significant part of toxic products from industries or the craft industry.
      Nitrifying activity can be affected by these substances, implying higher ammonia
      concentrations in the outlet effluent and contributing to toxicity for the
      aquatic environment. Moreover, the more stringently treated wastewater standards
      now require a reliable treatment for nitrogen. One of the key issues is the
      identification of the inhibition behavior of nitrifying bacteria facing a toxic
      substance. This new understanding could then finally be integrated into models in
      order to represent and to optimize wastewater treatment plants (WWTP) operation
      in cases involving 'toxic scenarios'. MATERIALS AND METHODS: The toxic substances
      studied in this work, cadmium and 3.5-dichlorophenol (3.5-DCP), are
      representative of chemical substances commonly found in municipal sewage and
      industrial effluents and symbolize two different contaminant groups. The effects
      of Cd and 3.5-DCP on nitrification kinetics have been investigated using
      respirometry techniques. RESULTS: IC50 values determination gives concentrations
      of 3.1 mg/L for 3.5-DCP and 45.8 mg/L for Cd at 21 +/- 1 degrees C. The variation
      to low temperature seems to have no real effect on IC50 for DCP, but induces a
      decrease of cadmium IC50 to 27.5 mg/L at 14 degrees C. Finally, specific
      respirometric tests have been carried out in order to determine the potential
      effect of these toxic substances on the nitrifying decay rate b ( a ). No
      significant effect has been noticed for Cd, whereas the presence of 3.5-DCP (at
      IC50 concentration) induced a dramatic increase of b ( a ) at 20 degrees C. The
      same behavior has been confirmed by experiments performed in winter periods with
      a sludge temperature around 12 degrees C. DISCUSSION: The target substances have
      different modes of action on activity and mortality, notably due to the abilities
      of the contaminant to be precipitated, accumulated, or even to be progressively
      degraded. Studies realized at low temperature confirmed this assumption, and put
      in evidence the effect of temperature on toxic substances capable of being
      biosorbed. However, the change in the sludge sample characteristics can be
      pointed out as a problem in the investigation of the temperature effect on
      nitrification inhibition, as biosorption, bioaccumulation, and predation are
      directly linked to the sludge characteristics (VSS concentration, temperature)
      and the plant operating conditions (loading rates, sludge age, etc.).
      CONCLUSIONS: This work brings new understandings concerning the action mode of
      these specific contaminants on nitrifying bacteria and, in particular, on the
      role of temperature. The experiments lead to the determination of the IC50 values
      for both toxic substances on biological nitrification. The inhibition mechanisms
      of Cd and 3.5-DCP on nitrifying activity have been simply represented by a non
      competitive inhibition model. RECOMMENDATIONS AND PERSPECTIVES: Other experiments
      carried out in a continuous lab-scale pilot plant should be done with a proper
      control of the operating conditions and of the sludge characteristics in order to
      better understand the mechanisms of nitrification inhibition for each
      contaminant. Finally, these first results show that toxic substances can have an
      effect on the growth rate but also on the decay rate, depending on the
      characteristics of the toxic substance and the sludge. This eventual double
      effect would imply different strategies of WWTP operation according to the
      behavior of the contaminant on the bacteria.

PMID- 18716817
TI  - Tikhonov regularized solutions for improvement of signal-to-noise ratio in case
      of auditory-evoked potentials.
AB  - In the present study, standard Tikhonov regularization (STR) Technique and the
      subspace regularization (SR) method have been applied to remove the additive EEG
      noise on average auditory-evoked potential (EP) signals. In methodological
      manner, the difference between these methods is the formation of regularization
      matrices which are used to solve the weighted problem of EP estimation. Those
      methods are compared to ensemble averaging (EA) with respect to signal-to-noise
      ratio (SNR) improvement in experimental studies, simulations and pseudo
      simulations. The results of tests no superiority of the SR in comparison to STR
      has been observed. In addition, the STR is found to be less computational
      complex. Moreover, results support the theoretical fact that the STR was
      introduced to be optimum for smooth solutions whereas the SR allows sharp
      variations in solutions. Thus, the STR is found to be more useful in removing the
      noise with the average signal remaining.

PMID- 18716819
TI  - A comparison of sexual and asexual replication strategies in a simplified model
      based on the yeast life cycle.
AB  - This paper develops simplified mathematical models describing the mutation
      selection balance for the asexual and sexual replication pathways in
      Saccharomyces cerevisiae, or Baker's yeast. The simplified models are based on
      the single-fitness-peak approximation in quasispecies theory. We assume diploid
      genomes consisting of two chromosomes, and we assume that each chromosome is
      functional if and only if its base sequence is identical to some master sequence.
      The growth and replication of the yeast cells is modeled as a first-order
      process, with first-order growth rate constants that are determined by whether a
      given genome consists of zero, one, or two functional chromosomes. In the asexual
      pathway, we assume that a given diploid cell divides into two diploids. For the
      sake of generality, our model allows for mitotic recombination and asymmetric
      chromosome segregation. In the sexual pathway, we assume that a given diploid
      cell divides into two diploids, each of which then divide into two haploids. The
      resulting four haploids enter a haploid pool, where they grow and replicate until
      they meet another haploid with which to fuse. In the sexual pathway, we consider
      two mating strategies: (1) a selective strategy, where only haploids with
      functional chromosomes can fuse with one another; (2) a random strategy, where
      haploids randomly fuse with one another. When the cost for sex is low, we find
      that the selective mating strategy leads to the highest mean fitness of the
      population, when compared to all of the other strategies. When the cost for sex
      is low, sexual replication with random mating also has a higher mean fitness than
      asexual replication without mitotic recombination or asymmetric chromosome
      segregation. We also show that, at low replication fidelities, sexual replication
      with random mating has a higher mean fitness than asexual replication, as long as
      the cost for sex is low. If the fitness penalty for having a defective chromosome
      is sufficiently high and the cost for sex sufficiently low, then at low
      replication fidelities the random mating strategy has a mean fitness that is a
      factor of square root 2 larger than the asexual mean fitness. We argue that for
      yeast, the selective mating strategy is the one that is closer to reality, which
      if true suggests that sex may provide a selective advantage under considerably
      more relaxed conditions than previous research has indicated. The results of this
      paper also suggest that S. cerevisiae switches from asexual to sexual replication
      when stressed, because stressful growth conditions provide an opportunity for the
      yeast to clear out deleterious mutations from their genomes. That being said, our
      model does not contradict theories for the evolution of sex that argue that sex
      evolved because it allows a population to more easily adapt to changing
      conditions.

PMID- 18716818
TI  - A striking parallel between cardiolipin fatty acid composition and phylogenetic
      belonging in marine bivalves: a possible adaptative evolution?
AB  - Thirty-five species of marine mollusk bivalves were analyzed for their fatty acid
      (FA) composition of cardiolipin (Ptd(2)Gro). All species showed a Ptd(2)Gro with
      strong selectivity for only a few polyunsaturated fatty acids, but three
      characteristic FA profiles emerged, with clear parallels to bivalve phylogeny. A
      first group of 12 species belonging to the Eupteriomorphia subgroup
      (Filibranchia) was characterized by a Ptd(2)Gro almost exclusively composed of
      22:6n-3, whereas in the four Filibranchia Pteriomorph species analyzed, this FA
      was combined with substantial proportions of 18:2n-6 and 18:3n-3. Finally, a
      third group of 20 species, all belonging to the Heterodonta subclass, possessed
      Ptd(2)Gro containing predominantly both 22:6n-3 and 20:5n-3. Polyunsaturated FA
      moieties and arrangements in the Ptd(2)Gro of some marine species investigated in
      other classes of the mollusk phylum (Gastropoda, Polyplacophora) were found to be
      different. The present results suggest that the specific Ptd(2)Gro FA
      compositions in bivalves are likely to be controlled and conserved in species of
      the same phylogenetic group. Functional significances of the evolution of this
      mitochondrial lipid structure in bivalves are discussed.

PMID- 18716821
TI  - Bone health and back pain: what do we know and where should we go?
AB  - Bone health is generally not considered in patients who present with chronic back
      pain. Nonetheless, bone health and back pain share common genetic and
      environmental correlates suggesting a co-dependence. Evidence exists for a
      relationship between back pain and impaired bone health. Here we present the
      evidence, theoretic framework and clinical relevance. Bone health and back pain
      are important determinants of musculoskeletal health. Back pain experienced in
      youth is a risk factor for future back pain, while suboptimal bone health during
      development increases the risk of skeletal fragility in later life. Generally,
      bone health is not considered in patients with chronic back pain who do not
      demonstrate other well-recognised bone health risk factors or associated
      conditions. Nonetheless, evidence suggests that back pain and impaired bone
      health share common environmental and genetic correlates, indicating that bone
      health ought to be considered in the context of back pain in otherwise healthy
      individuals. This review describes the likely mechanisms explaining the
      relationship between back pain and impaired bone health, evidence concerning the
      relationship and suggestions for future research. A narrative literature search
      was conducted using CINAHL, Medline, PubMed and Web of Science electronic
      databases. A history of back pain is associated with decreased bone mineral
      density in adults, yet this tends to be site-specific. No studies were identified
      examining this association in youth, yet the negative effects of childhood
      skeletal trauma and obesity on bone and spinal health provide indirect evidence
      for an association. Further research is required to clarify the impact of back
      pain on bone health at different lifespan stages using prospective cohort
      designs.

PMID- 18716822
TI  - Alendronate treatment results in similar levels of trabecular bone remodeling in
      the femoral neck and vertebra.
AB  - SUMMARY: We aimed to determine whether trabecular bone in sites that have
      different surface-based remodeling rates, the femoral neck and vertebra, are
      differently affected by alendronate treatment. Alendronate treatment resulted in
      similar levels of turnover in both sites, suggesting that a lower limit of bone
      turnover suppression with alendronate may exist. INTRODUCTION: Bone turnover
      suppression in sites that already have a low surface-based remodeling rate may
      lead to oversuppression that could have negative effects on the biomechanical
      properties of bone. The goal was to determine how alendronate suppresses bone
      turnover at sites with different surface-based remodeling rates. METHODS: Dynamic
      histomorphometric parameters were assessed in trabecular bone of the femoral neck
      and lumbar vertebrae obtained from skeletally mature beagles treated with saline
      (1 ml/kg/day) or alendronate (ALN 0.2 or 1.0 mg/kg/day). The ALN0.2 and ALN1.0
      doses approximate, on a milligram per kilogram basis, the clinical doses used for
      the treatment of postmenopausal osteoporosis and Paget's disease, respectively.
      RESULTS: Alendronate treatment resulted in similar absolute levels of bone
      turnover in the femoral neck and vertebrae, although the femoral neck had 33%
      lower pre-treatment surface-based remodeling rate than the vertebra (p < 0.05).
      Additionally, the high dose of alendronate (ALN 1.0) suppressed bone turnover to
      similar absolute levels as the low dose of alendronate (ALN 0.2) in both sites.
      CONCLUSIONS: Alendronate treatment may result in a lower limit of trabecular bone
      turnover suppression, suggesting that sites of low pre-treatment remodeling rate
      are not more susceptible to oversuppression than those of high pre-treatment
      remodeling rate.

PMID- 18716823
TI  - The Osteoporosis Self-Assessment Tool versus alternative tests for selecting
      postmenopausal women for bone mineral density assessment: a comparative
      systematic review of accuracy.
AB  - SUMMARY: We performed a systematic review of studies comparing the Osteoporosis
      Self-Assessment Tool (OST) and other tests used to select women for bone mineral
      density (BMD) assessment. In comparative meta-analyses, we found that the
      accuracy of OST was similar to other tests that are based on information from the
      medical history. By contrast, assessment by quantitative ultrasonography at the
      heel was more accurate than OST in discriminating between women with high and low
      BMD. The methodological quality of the included studies was generally low.
      INTRODUCTION: Numerous tests are suggested for triaging postmenopausal women for
      bone mineral density (BMD) assessment by dual-energy X-ray absorptiometry.
      Previous studies suggest that OST, based on age and weight only, may be as
      accurate as more complex triage tests. We systematically compare the accuracy of
      OST and alternative triage tests in postmenopausal women. METHODS: We searched
      PubMed, Embase, Web of Science, citation lists, and conference proceedings. Our
      main measure of accuracy was the diagnostic odds ratio (DOR). We compared summary
      estimates of DOR (sDOR) for OST and alternative tests in pairwise meta-analyses
      by using the Moses-Littenberg approach. RESULTS: Summary estimates of DOR for OST
      and the clinical decision rules Simple Calculated Osteoporosis Risk Estimation
      (SCORE) and Osteoporosis Risk Assessment Instrument (ORAI) did not differ
      significantly in white women (relative sDOR: 0.57-1.17, all p >or= 0.11). By
      contrast, sDOR was higher for Stiffness Index assessed by calcaneal quantitative
      ultrasonography than for OST (relative sDOR: 1.9, p = 0.005). Studies were few in
      Asian and black women. Methodological quality, assessed with the Quality
      Assessment of Diagnostic Accuracy Studies (QUADAS) checklist, was generally low.
      CONCLUSIONS: In white women, the accuracy of OST and alternative clinical
      decision rules was similar, whereas Stiffness Index was more accurate than OST.
      Low study quality renders transferability to clinical settings uncertain.

PMID- 18716825
TI  - A feasibility study on laser rapid forming of a complete titanium denture base
      plate.
AB  - This work attempted to integrate the technologies of computer-aided design and
      computer-aided manufacture (CAD/CAM) and laser rapid forming (LRF) for the
      fabrication of the titanium plate of a complete denture. By the combination of
      laser scan and reverse engineering software, the standard triangulation language
      (STL)-formatted denture base plate was finally designed and sliced into a
      sequence of numerical controlled codes. The titanium (Ti) complete denture plate
      was finally built, layer-by-layer, on the LRF system. To evaluate the quality of
      fit, a virtual adaptation test that measured and compared the profiles of the
      laser free formed denture plate and those of the edentulous plaster cast had been
      conducted, and the mean deviation was found to be 0.34 mm. After traditional
      dental finishing techniques, a complete denture with a Ti base plate was then
      made and judged to be acceptable. The CAD/CAM/LRF system is a potential candidate
      and a new platform for the design and manufacture of custom-made Ti denture
      plates and restorations.

PMID- 18716824
TI  - Effect of equal daily doses achieved by different power densities of low-level
      laser therapy at 635 nm on open skin wound healing in normal and corticosteroid
      treated rats.
AB  - Optimal parameters of low-level laser therapy (LLLT) for wound healing are still
      discussed. Hence, our study was aimed to compare effects of different power
      densities of LLLT at 635 nm in rats. Four, round, full-thickness, skin wounds
      were made on the backs of 48 rats that were divided into two groups (non-steroid
      laser-treated and steroid laser-treated). Three wounds were stimulated daily with
      a diode laser (daily dose 5 J/cm(2)) each with different power density (1
      mW/cm(2), 5 mW/cm(2), and 15 mW/cm(2)), whereas the fourth wound served as a
      control. Two days, 6 days, and 14 days after surgery, eight animals from each
      group were killed and samples were removed for histological evaluation. In the
      non-steroid laser-treated rats, significant acceleration of epithelization and
      collagen synthesis 2 days and 6 days after surgery was observed in stimulated
      wounds. In steroid laser-treated rats, 2 days and 14 days after surgery, a
      decreased leucocyte/macrophage ratio and a reduction in the area of granulation
      tissue were recorded, respectively. In conclusion, LLLT, by the method we used,
      improved wound healing in the non-steroid laser-treated rats, but it was useless
      after corticosteroid treatment.

PMID- 18716826
TI  - Adhesives bonded to erbium:yttrium-aluminum-garnet laser-irradiated dentin:
      transmission electron microscopy, scanning electron microscopy and tensile bond
      strength analyses.
AB  - The aim of this in vitro study was to investigate the effect of erbium:yttrium
      aluminum-garnet (Er:YAG) laser irradiation on dentinal collagen by transmission
      electron microscopy and to analyze the resin-dentin interface by scanning
      electron microscopy. A tensile bond strength test was also applied. Specimens
      from 69 sound human third molars were randomly divided into three groups: control
      (no laser), and two irradiated groups, laser 250 (250 mJ/2 Hz) and laser 400 (400
      mJ/4 Hz). Then, specimens were restored with two adhesive systems, an etch-and
      rinse or a self-etch system. Although ultrastructural examination showed a
      modified surface in the irradiated dentin, there was no statistical difference in
      bond strength values between the laser groups and controls (P < 0.05). In
      conclusion, the use of Er:YAG laser for ablating human dentin did not alter the
      main adhesion parameters when compared with those obtained by conventional
      methods, thus reinforcing its use in restorative dentistry.

PMID- 18716827
TI  - A clinical comparison of topical piroxicam and EMLA cream for pain relief and
      inflammation in laser hair removal.
AB  - The aim of this study was to compare the efficacy of topical piroxicam and EMLA
      cream on pain control and subsequent inflammation in neodymium:yttrium-aluminum
      garnet (Nd:YAG) 1,064 nm laser hair removal in female volunteers. Fifty female
      volunteers were enrolled in this prospective, randomized, double-blind, clinical
      study over a 6-month period. Patients were randomly assigned to receive topical
      piroxicam as group Piroxicam or EMLA cream as group EMLA. Topical analgesics were
      applied to the treatment sites for 60 min. The pain scores [on a visual analog
      scale (VAS)] and side effects were recorded before the hair removal, during the
      hair removal, at the end of the hair removal, and 1 h, 2 h and 24 h after the
      hair removal. Patients' characteristics and the treatment settings of the Nd:YAG
      1,064 nm laser were similar in the two groups. The pain scores (VAS) were
      similar, and satisfaction was high in both groups after the hair removal. The
      number of blanching and erythema episodes were significantly higher in group E
      than in group P (P < 0.001). Inflammatory side effects were less frequent in
      group P than in group E after the procedure (P < 0.001). This study showed that
      topical piroxicam and EMLA provided adequate and similar pain relief after Nd:YAG
      1,064 nm laser hair removal in female volunteers. Topical piroxicam was
      associated with fewer inflammatory side effects than was EMLA cream, because of
      its anti-inflammatory effect after the procedure.

PMID- 18716828
TI  - Microleakage of glass ionomer formulations after erbium:yttrium-aluminium-garnet
      laser preparation.
AB  - The aim of this study was to investigate the microleakage in class V cavities
      restored with four conventionally setting glass ionomers (CGIs) and one resin
      modified glass ionomer (RMGI) following erbium:yttrium-aluminium-garnet (Er:YAG)
      laser or conventional preparation. Four hundred class V cavities were assigned to
      four groups: A and B were prepared by an Er:YAG laser; C and D were
      conventionally prepared. In groups B and D, the surface was additionally
      conditioned with Ketac conditioner. Each group was divided into five subgroups
      according to the glass ionomer cement (GIC) used: groups 1 (Ketac Fil), 2 (Ketac
      Molar), 3 (Ionofil Molar), 4 (Ionofil Molar Quick) and 5 (Photac Fil Quick).
      After thermocycling, a 2% methylene blue solution was used as dye. Scanning
      electron microscope (SEM) photographs were taken to show the conditioner's
      effect. Complete marginal sealing could not be reached. PhotacFil showed less
      microleakage than the conventionally setting glass ionomer cements (CGICs)
      investigated. Conditioning laser-prepared cavities did not negatively influence
      microleakage results except for Ionofil Molar Quick.

PMID- 18716829
TI  - Benefits of liver transplantation surgical techniques in the management of
      extensive retroperitoneal tumors.
AB  - BACKGROUND: The potential for massive hemorrhage imposes additional challenge in
      the management of retroperitoneal tumors. This report details technical
      considerations for the management of upper retroperitoneal tumors using
      principles of liver transplantation. METHODS: A retrospective chart review of
      patients who underwent surgery for extensive retroperitoneal tumors using
      techniques for liver transplantation from December 2002 to November 2007 was
      done. RESULTS: Twenty-four patients (14 males and 10 females with a mean age 57
      years) underwent major retroperitoneal surgery. Renal cell carcinoma was the most
      common tumor seen in 17 patients. Mean tumor dimension was 12.4 cm. Abdominal
      exposure was achieved via bilateral subcostal incision with upper midline
      extension. Right hepatic lobe mobilization and isolation from the inferior vena
      cava (IVC) was performed in 23 cases. Fourteen patients had IVC involvement by
      tumor thrombus, which was infrahepatic in six, retrohepatic in five, and intra
      atrial in three patients. Tumor thrombus was removed by cavotomy in seven cases,
      resection and plasty in four cases, IVC graft reconstruction in two cases, and
      one patient required IVC and atrial graft reconstruction. Liver resection was
      needed in seven patients to achieve R0 resection. The Pringle maneuver was used
      in three patients; total liver vascular isolation with venovenous bypass was
      required in two cases, transdiaphragmatic intrapericardial IVC control in one
      case, and cardiopulmonary bypass in one patient. There was no intraoperative or
      postoperative mortality and mean length of stay was 13 days. CONCLUSION: Liver
      transplantation surgical principles help achieve exposure and vascular control of
      major vascular structures that enable safe resection of these extensive
      retroperitoneal tumors.

PMID- 18716830
TI  - Cost-effectiveness of a district trauma hospital in Battambang, Cambodia.
AB  - BACKGROUND: The Emergency Hospital in Battambang, Cambodia, is essentially a
      surgical center for victims of injuries. METHODS: Using methods previously
      described, operating costs were calculated, and effectiveness of treatment was
      estimated for 957 patients undergoing 895 surgical procedures over a 3 month
      period (October--December 2006). RESULTS: Results of the cost-effectiveness
      analysis are compared to the few existing ones in the literature. CONCLUSION: At
      $77.4 per DALY averted, surgery for trauma in such a context is deemed very cost
      effective and compares favorably to other non-surgical public health
      interventions.

PMID- 18716831
TI  - Surgical factors influencing outcomes in patients resected for cancer of the
      esophagus or gastric cardia.
AB  - BACKGROUND: Surgery is the treatment of choice for localized esophageal and
      gastric cardia cancer. Our aim was to evaluate factors influencing postoperative
      short-term morbidity, 30-day mortality, and long-term prognosis. METHODS: We
      identified 232 patients who had undergone surgical resection from a Swedish
      nationwide case control study of cancer of the esophagus and cardia between
      December 1, 1994 and December 31, 1997. Patients' demographics, tumor
      characteristics, preoperative investigations, and treatments were reviewed.
      Patients were followed up through linkage to the Death Registry until December
      2004. Survival curves were estimated by the Kaplan-Meier method. Cox proportional
      hazards regression models were used to derive hazard ratios (HRs) with 95%
      confidence intervals (CIs). RESULTS: The overall 5-year survival rate was 25%.
      Tumor stage was the most prominent prognostic factor for long-term survival. Low
      volume hospital (HR = 1.3, 95% CI = 1.0-1.9), low-volume surgeon (HR = 1.4, 95%
      CI = 1.0-2.0), and postoperative need for respirator support (HR = 1.4, 95% CI =
      1.0-1.9), were associated with a worse prognosis. Patients treated at low-volume
      hospitals or by low-volume surgeons needed respirator support more often or
      stayed longer at intensive care units after surgery. CONCLUSION: Patients with
      esophageal cancer have a modestly poorer prognosis when operated on at low-volume
      centers or by surgeons with less experience with esophageal cancer surgery.

PMID- 18716832
TI  - Inhibition of vancomycin and high-level aminoglycoside-resistant enterococci
      strains and Listeria monocytogenes by bacteriocin-like substance produced by
      Enterococcus faecium E86.
AB  - Three hundred and thirty nine lactic bacteria strains isolated from food samples
      were screened for antimicrobial activity. Only one strain isolated from meat pie
      and identified as Enterococcus faecium produced a bacteriocin-like inhibitory
      substance (BLIS) showing activity against Enterococcus, Leuconostoc,
      Lactobacillus, Listeria, Corynebacterium and Staphylococcus aureus. The BLIS
      produced was resistant to acid and alkali treatment and 121 masculineC for 15
      min. The addition of BLIS in BHI contaminated with Listeria monocytogenes
      decreased the contamination in 4.8 log cycles in 24 h. The inhibition of listeria
      was also obtained in milk. Forty multiresistant enterococci strains were
      inhibited in the well-diffusion test. Two vancomycin resistant strains tested in
      liquid with BLIS were also inhibited. The BLIS producer showed no pathogenicity
      marker.

PMID- 18716833
TI  - The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful
      resource for systems genetics.
AB  - Complex traits and disease comorbidity in humans and in model organisms are the
      result of naturally occurring polymorphisms that interact with each other and
      with the environment. To ensure the availability of resources needed to
      investigate biomolecular networks and systems-level phenotypes underlying complex
      traits, we have initiated breeding of a new genetic reference population of mice,
      the Collaborative Cross. This population has been designed to optimally support
      systems genetics analysis. Its novel and important features include a high level
      of genetic diversity, a large population size to ensure sufficient power in high
      dimensional studies, and high mapping precision through accumulation of
      independent recombination events. Implementation of the Collaborative Cross has
      been ongoing at the Oak Ridge National Laboratory (ORNL) since May 2005.
      Production has been systematically managed using a software-assisted breeding
      program with fully traceable lineages, performed in a controlled environment.
      Currently, there are 650 lines in production, and close to 200 lines are now
      beyond their seventh generation of inbreeding. Retired breeders enter a high
      throughput phenotyping protocol and DNA samples are banked for analyses of
      recombination history, allele drift and loss, and population structure. Herein we
      present a progress report of the Collaborative Cross breeding program at ORNL and
      a description of the kinds of investigations that this resource will support.

PMID- 18716834
TI  - Establishment of "The Gene Mine": a resource for rapid identification of complex
      trait genes.
AB  - Identification of genes underlying complex traits presents a challenge to which
      geneticists have responded with many diverse approaches. A common feature of
      these approaches is that different research groups must, on a case-by-case basis,
      replicate similar efforts in recruitment, genetic characterization, and analyses.
      To avoid this expensive "churning," an alternative approach has been proposed:
      production of an experimental genetic reference population, the Collaborative
      Cross, in which both genetic diversity and mapping power are maximized. Since
      this population consists of inbred mouse strains, further advantages are that it
      is essentially infinitely reproducible; genetic characterization needs to be
      performed only once; and the founder strains' genomes have been or will be
      sequenced, allowing imputation of allele sequences of all members of the
      reference population. Here we describe the establishment of such a genetic
      reference population, which we dub "The Gene Mine." Over 1000 genetically
      distinct lines have been established, descended from eight diverse founder
      strains. Preliminary phenotypic ascertainment of these strains indicates
      unexpected variability arising from independent assortment of genetic variants.
      The Gene Mine will be a powerful resource for characterization of essentially any
      mouse phenotype that has a genetic basis.

PMID- 18716835
TI  - Racial differences in sarcoidosis granuloma density.
AB  - STUDY OBJECTIVES: While sarcoidosis generally inflicts a greater morbidity on
      African-American compared with Caucasian patients, no studies have examined
      whether racial differences exist in the intensity of the histologic hallmark of
      sarcoidosis, noncaseating granulomas. DESIGN AND SETTING: The study was conducted
      as a retrospective case series in a tertiary referral center. PATIENTS: The study
      included 187 patients with histopathologic confirmation of sarcoidosis by trans-
      and/or endobronchial biopsy between July 1991 and December 2001. MEASUREMENTS AND
      RESULTS: Granuloma density was the average number of granulomas per biopsy piece
      on the slide with the most intense granulomatous inflammation at fourfold
      magnification. Overall, African-American patients had a twofold greater median
      granuloma density than Caucasians (p = 0.005). In a negative binomial
      multivariate model, radiographic pattern had the strongest association with
      granuloma density, with Scadding stage II and III patients having adjusted
      granuloma densities of 60% (p = 0.005) and 105% (p = 0.0001) higher than stage I
      patients. In the specific-tissue types, radiographic stage-adjusted granuloma
      densities in African-American patients were 49% greater in bronchial tissue (p =
      0.03), but only a 27% greater in alveolar tissue (p = 0.51). CONCLUSIONS: A
      greater granuloma density in bronchiolar lung tissue of African-American
      sarcoidosis patients may explain racial differences in diagnostic yield by lung
      biopsy and disease severity at diagnosis. This association persists even after
      controlling for Scadding radiographic stage, a measure of disease severity
      strongly associated with granuloma density.

PMID- 18716836
TI  - Influence of craniofacial morphology on hyoid movement: a preliminary
      correlational study.
AB  - There has been little attention given to the relationship between variations in
      normal craniofacial morphology and swallowing physiology. This preliminary
      investigation evaluated the relationship between the Frankfort-mandibular plane
      angle (FMA) and hyoid displacement during swallowing. Hyoid movement was
      evaluated during 12-ml and 24-ml swallows of liquid barium in 12 healthy subjects
      (age = 20-29 years, median = 23 years). Lateral projection videofluorography was
      utilized. Positions of the hyoid at maximum forward displacement, maximum upward
      displacement, starting position, and ending position were determined using image
      analysis software. The mean FMA was 28.92 degrees +/- 4.08 degrees (mean +/- SD,
      range = 20 degrees -34 degrees ). A Pearson correlation (<or=0.05) demonstrated
      that hyoid forward displacement was significantly inversely correlated with the
      FMA [R = -0.68, p = 0.015 (12 ml) and R = -0.72, p = 0.009 (24 ml)]; thus, the
      greater the FMA, the smaller the hyoid forward displacement. Upward displacement
      of the hyoid was not significantly correlated with FMA for 12-ml (R = -0.41, p =
      0.55) or 24-ml swallows (R = 0.21, p = 0.512). In addition, there was no
      significant correlation between hyoid starting or ending positions. In
      conclusion, the results of this preliminary study suggest that normal variations
      in morphology, as measured by the FMA, may influence hyoid movement and therefore
      affect swallowing physiology.

PMID- 18716837
TI  - The effects of aging on hypoglossal motoneurons in rats.
AB  - Aging can result in a loss of neuronal cell bodies and a decrease in neuronal
      size in some regions of the brain and spinal cord. Motoneuron loss in the spinal
      cord is thought to contribute to the progressive decline in muscle mass and
      strength that occurs with age (sarcopenia). Swallowing disorders represent a
      large clinical problem in elderly persons; however, age-related alterations in
      cranial motoneurons that innervate muscles involved in swallowing have been
      understudied. We aimed to determine if age-related alterations occurred in the
      hypoglossal nucleus in the brainstem. If present, these changes might help
      explain alterations at the neuromuscular junction and changes in the contractile
      properties of tongue muscle that have been reported in older rats. We
      hypothesized that with increasing age there would be a loss of motoneurons and a
      reduction in neuronal size and the number of primary dendrites associated with
      each hypoglossal motoneuron. Neurons in the hypoglossal nucleus were visualized
      with the neuronal marker NeuN in young (9-10 months), middle-aged (24-25 months),
      and old (32-33 months) male F344/BN rats. Hypoglossal motoneurons were retrograde
      labeled with injections of Cholera Toxin beta into the genioglossus muscle of the
      tongue and visualized using immunocytochemistry. Results indicated that the
      number of primary dendrites of hypoglossal motoneurons decreased significantly
      with age, while no age-associated changes were found in the number or size of
      hypoglossal motoneurons. Loss of primary dendrites could reduce the number of
      synaptic inputs and thereby impair function.

PMID- 18716838
TI  - Role of cerebral cortex plasticity in the recovery of swallowing function
      following dysphagic stroke.
AB  - Effective swallowing is an essential part of life and is performed thousands of
      times per day, often without conscious consideration. Difficulty in swallowing
      (dysphagia) commonly arises in stroke patients following ischemia of the cerebral
      cortex. However, whereas this tends to resolve spontaneously in the majority of
      patients, a small percentage will be left with a persistent dysphagia, which
      predisposes to airway compromise and aspiration pneumonia. This article reviews
      the recent research into ways of restoring swallowing function in these patients
      through promoting plasticity and reorganisation of the remaining, viable cerebral
      cortex.

PMID- 18716840
TI  - Ciguatera fish poisoning in la Habana, Cuba: a study of local social-ecological
      resilience.
AB  - Following the collapse of the Cuban economy in the early 1990s, epidemiologists
      in the Cuban Ministry of Health noticed dramatic increases in reported outbreaks
      of ciguatera fish poisoning (CFP) in some coastal communities. This article
      summarizes the results of a comparative case study which applied an ecosystem
      approach to human health to investigate this issue. Situated learning and
      complexity theories were used to interpret the results of the investigation. CFP
      outbreaks are influenced by a complex set of interactions between ecological and
      socioeconomic processes. This study found that the level of organization of the
      local sports fishing community and the degree of degradation of the local
      nearshore marine ecosystem appear to be key factors influencing the diverging
      levels of CFP outbreaks recorded in the 1990s in the communities studied.

PMID- 18716839
TI  - Creation and usability testing of a web-based pre-scanning radiology patient
      safety and history questionnaire set.
AB  - Recent advances in technology have significantly changed radiology workflow. The
      main focus of these changes has been the transition from hard copy film to
      digital imaging. The next transition will be a "paperless" transformation. Web
      based versions of the current paper-based patient safety and history
      questionnaires were created using PHP and MySQL. Two rounds of usability testing
      using volunteers were completed using tablet PCs. Volunteers were comprised of
      ten individuals. Ages of volunteers ranged from 27 to 60 years, and there were
      eight males and two females. The majority of users had at least a Master's degree
      and was considered to have a computer experience level of a programmer. Eighty
      percent of the users agreed that the web-based questionnaires and tablet PCs were
      easy to use. Text input through the writing recognition window and scrolling
      proved to be the least usable sections of the questionnaires. The new web-based
      system was found to be a very usable system by our participants. The
      questionnaires were easy to use, easy to navigate, and easy to read. Individual
      elements such as radio buttons and checkboxes did not fair as well but were due
      to their small size. Difficulty with the writing recognition interface is an
      inherent issue with the Windows XP Tablet Edition operating system.

PMID- 18716841
TI  - Quality of life after potentially curative treatment for locally advanced rectal
      cancer.
AB  - BACKGROUND: Patients with locally advanced rectal cancer have a poor prognosis
      and the early and late postoperative morbidity is high. The aim of this study was
      to assess health-related quality of life (HRQL) in patients treated with
      extensive surgical resections for locally advanced rectal cancer and to compare
      the results with those in patients treated for primarily resectable rectal
      cancer. METHODS: Between 1991 and 2003, 142 patients with locally advanced rectal
      cancer had an extensive resection at the Karolinska Hospital in Stockholm,
      Sweden. A HRQL assessment with the European Organization for Research and
      Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR38 questionnaires was performed in
      patients alive and disease free in 2005. The results were compared with an age-
      and sex-matched reference group of patients with primarily resectable rectal
      cancer having had total mesorectal excision alone. RESULTS: The study group of 43
      patients (81% of eligible) scored clinically and statistically significantly
      lower in global quality of life, role function, physical function, social
      function, and body image and reported a higher degree of pain and fatigue
      compared with the reference group of 80 patients. In the study group, men scored
      lower than women in global quality of life, role functioning and social
      functioning and reported more problems with fatigue. CONCLUSION: Several aspects
      of HRQL are impaired in disease-free patients treated for locally advanced rectal
      cancer. This knowledge may be useful in the preoperative counselling and
      postoperative support of these patients.

PMID- 18716842
TI  - CTLA-4 blockade with monoclonal antibodies in patients with metastatic cancer:
      surgical issues.
AB  - BACKGROUND: CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) is a modulatory
      receptor on T cells involved in downregulating T cell activation. In animal
      models, CTLA-4 blockade abrogates tolerance to "self" antigens, resulting in the
      augmentation of antitumor immunity and induction of autoimmunity. CTLA-4 blockade
      by means of monoclonal antibodies (ipilimumab and tremelimumab) has been
      evaluated in multiple clinical trials in patients with metastatic cancer, mainly
      those with melanoma and renal cell cancer. METHODS: We examine available
      literature and ongoing clinical trials with ipilimumab and tremelimumab and
      review our own experience with patients treated with CTLA-4 blockade, with an
      emphasis on issues of direct relevance to surgical oncologists. RESULTS: CTLA-4
      blockade can cause durable tumor regression in patients with metastatic melanoma
      and other solid tumors. Grade III/IV autoimmune toxicity has been frequently
      encountered in clinical trials and includes enterocolitis, dermatitis,
      hypophysitis, uveitis, and hepatitis. Enterocolitis is the most common immune
      related adverse event and may cause severe diarrhea requiring intravenous
      hydration, high-dose corticosteroids, and blockade of tumor necrosis factor alpha
      with infliximab. Most patients respond to medical treatment, but up to 12% with
      grade III/IV enterocolitis develop perforation or bleeding that requires
      colectomy. CONCLUSIONS: As more patients are enrolled onto clinical trials
      involving ipilimumab and tremelimumab, an increasing number of surgeons may be
      involved in the care of these patients who develop treatment-related
      complications. In this report, we review the rationale for CTLA-4 blockade and
      review selected clinical studies published so far with ipilimumab and
      tremelimumab. We offer guidelines on the management of patients who develop
      enterocolitis.

PMID- 18716843
TI  - Mathematical model for low density lipoprotein (LDL) endocytosis by hepatocytes.
AB  - Individuals with elevated levels of plasma low density lipoprotein (LDL)
      cholesterol (LDL-C) are considered to be at risk of developing coronary heart
      disease. LDL particles are removed from the blood by a process known as receptor
      mediated endocytosis, which occurs mainly in the liver. A series of classical
      experiments delineated the major steps in the endocytotic process; apolipoprotein
      B-100 present on LDL particles binds to a specific receptor (LDL receptor, LDL-R)
      in specialized areas of the cell surface called clathrin-coated pits. The pit
      comprising the LDL-LDL-R complex is internalized forming a cytoplasmic endosome.
      Fusion of the endosome with a lysosome leads to degradation of the LDL into its
      constituent parts (that is, cholesterol, fatty acids, and amino acids), which are
      released for reuse by the cell, or are excreted. In this paper, we formulate a
      mathematical model of LDL endocytosis, consisting of a system of ordinary
      differential equations. We validate our model against existing in vitro
      experimental data, and we use it to explore differences in system behavior when a
      single bolus of extracellular LDL is supplied to cells, compared to when a
      continuous supply of LDL particles is available. Whereas the former situation is
      common to in vitro experimental systems, the latter better reflects the in vivo
      situation. We use asymptotic analysis and numerical simulations to study the
      longtime behavior of model solutions. The implications of model-derived insights
      for experimental design are discussed.

PMID- 18716844
TI  - A dynamical low-rank approach to the chemical master equation.
AB  - Stochastic reaction kinetics have increasingly been used to study cellular
      systems, with applications ranging from viral replication to gene regulatory
      networks and to signaling pathways. The underlying evolution equation, known as
      the chemical master equation (CME), can rarely be solved with traditional methods
      due to the huge number of degrees of freedom. We present a new approach to
      directly solve the CME by a dynamical low-rank approximation based on the Dirac
      Frenkel-McLachlan variational principle. The new approach has the capability to
      substantially reduce the number of degrees of freedom, and to turn the CME into a
      computationally tractable problem. We illustrate the accuracy and efficiency of
      our methods in application to two examples of biological interest.

PMID- 18716845
TI  - The potential impact of disease on the migratory structure of a partially
      migratory passerine population.
AB  - Since its introduction into eastern North America in the 1940s, the eastern
      population of house finches (Carpodacus mexicanus) has become partially
      migratory, unlike its nonmigratory source population in southern California (Able
      and Belthoff in Proc. R. Soc. Lond. 265 (1410), 2063-2071, 1998; Belthoff and
      Gauthreaux in Condor 93, 374-382, 1991). The infectious disease mycoplasmal
      conjunctivitis (pathogen Mycoplasma gallisepticum or "MG"), which has been
      monitored in the house finch population since its appearance around 1993 (Dhondt
      et al. in J. Wild. Dis. 34 (2), 265-280, 1998), may induce higher mortality rates
      among populations in more northerly latitudes relative to more southerly
      populations. Here, we investigate the potential impact of this differential
      disease mortality on the migratory structure of the eastern house finch
      population using an epidemic modeling approach. Analytical and computational
      results suggest the ongoing MG epidemic in the eastern house finch could lead to
      increases in the percentage of and the total number of migrating individuals in a
      population despite overall population declines, assuming relatively high winter
      mortality rates in the north eastern part of their range. These results also
      suggest that empirical evidence of such a change in migratory structure would be
      most noticeable in northerly inland populations that showed significant declines
      following the initial outbreak of MG in the east.

PMID- 18716846
TI  - Mathematical model of pulsed immunotherapy for superficial bladder cancer.
AB  - We present a theoretical study of superficial bladder cancer growth and its
      treatment via pulsed immunotherapy with Bacillus Calmette-Guerin (BCG), an
      attenuated strain of Mycobacterium bovis. BCG pulsed immunotherapy is a
      clinically established procedure for the treatment of superficial bladder cancer.
      In this paper, periodic BCG instillations are modeled using impulsive
      differential equations, which are studied using a combination of analytical and
      numerical techniques. In this way, we determine critical threshold values of the
      BCG instillation dose and rate of pulsing for successful treatment. We also
      identify treatment regimes in which tumor destruction occurs, but undesirable
      side effects are maintained at low levels by the immune system.

PMID- 18716847
TI  - Unhealthy drinking patterns and receipt of preventive medical services by older
      adults.
AB  - BACKGROUND: Preventive service use among older adults is suboptimal. Unhealthy
      drinking may constitute a risk factor for failure to receive these services.
      OBJECTIVES: To determine the relationship between unhealthy drinking and receipt
      of recommended preventive services among elderly Medicare beneficiaries, applying
      the framework of current alcohol consumption guidelines. DESIGN/METHODS: The data
      source is the nationally representative 2003 Medicare Current Beneficiary Survey.
      The sample included community-dwelling, fee-for-service Medicare beneficiaries 65
      years and older (N = 10,523). Based on self-reported drinking, respondents were
      categorized as nondrinkers, within-guidelines drinkers, exceeding monthly but not
      daily limits, or heavy episodic drinkers. Using survey and claims data, influenza
      vaccination, pneumonia vaccination, glaucoma screening, and mammogram receipt
      were determined. Bivariate and logistic regression analyses were conducted.
      RESULTS: Overall, 70.3% received flu vaccination and 49% received glaucoma
      screening during the year, 66.8% received pneumonia vaccination, and 56.2% of
      women received a mammogram over 2 years. In logistic regression, heavy episodic
      drinking was associated with lower likelihood of service receipt compared to
      drinking within guidelines: flu vaccination (OR 0.75, CI 0.59-0.96), glaucoma
      screening (OR 0.74, CI 0.58-0.95), and pneumonia vaccination (OR 0.75, CI 0.59
      0.96). Nondrinkers when compared with those reporting drinking within guidelines
      were less likely to receive a mammogram (OR 0.83, CI 0.69-1.00). CONCLUSIONS:
      Heavy episodic drinking is associated with lower likelihood of receiving several
      preventive services. Practitioners should be encouraged to screen all elders
      regarding alcohol intake and in addition to appropriate intervention, consider
      elders reporting heavy episodic drinking at higher risk for non-receipt of
      preventive services.

PMID- 18716848
TI  - National evaluation of policies on individual financial conflicts of interest in
      Canadian academic health science centers.
AB  - BACKGROUND: Conflicts of interest (COI) in research are an important emerging
      topic of investigation and are frequently cited as a serious threat to the
      integrity of human participant research. OBJECTIVE: To study financial conflicts
      of interest (FCOI) policies for individual investigators working in Canadian
      academic health centers. DESIGN: Survey instrument containing 61 items related to
      FCOI. SETTING: All Canadian academic health science centers (universities with
      faculties of medicine, faculties of medicine and teaching hospitals) were
      requested to provide their three primary FCOI policies. MEASUREMENTS: Number of
      all centers and teaching hospitals with policies addressing each of the 61 items
      related to FCOI. MAIN RESULTS: Only one item was addressed by all 74 centers.
      Thirteen items were present in fewer than 25% of centers. Fewer than one-quarter
      of hospitals required researchers to disclose FCOI to research participants. The
      role of research ethics boards (REBs) in hospitals was marginal. LIMITATIONS:
      Asking centers to identify only three policies may not have inclusively
      identified all FCOI policies in use. Additionally, policies at other levels might
      apply. For instance, all institutions receiving federal grant money must comply
      with the Tri-Council Policy Statement: Ethical Conduct for Research Involving
      Humans. CONCLUSIONS: Canadian centers within the same level (for instance,
      teaching hospitals) differ significantly in the areas that their policies address
      and these policies differ widely in their coverage. Presently, no single policy
      in any Canadian center informs researchers about the broad range of individual
      FCOI issues. Canadian investigators need to understand the environment
      surrounding FCOI, be able to access and follow the relevant policies and be
      confident that they can avoid entering into a FCOI.

PMID- 18716849
TI  - Reach and impact of a mass media event among vulnerable patients: the Terri
      Schiavo story.
AB  - BACKGROUND: It is unknown whether health-related media stories reach diverse
      older adults and influence advance care planning (ACP). OBJECTIVE: To determine
      exposure to media coverage of Terri Schiavo (TS) and its impact on ACP. DESIGN
      AND PARTICIPANTS: Descriptive study of 117 English/Spanish-speakers, aged >or=50
      years (mean 61 years) from a county hospital, interviewed six months after
      enrollment into an advance directive study. MEASUREMENTS: We assessed whether
      participants had heard of TS and subject characteristics associated with
      exposure. We also asked whether, because of TS, subjects engaged in ACP. MAIN
      RESULTS: Ninety-two percent reported hearing of TS. Participants with adequate
      literacy were more likely than those with limited literacy to report hearing of
      TS (100% vs. 79%, P < .001), as were participants with >or= a high school vs. <
      high school education (97% vs. 82%, P = .004), and English vs. Spanish-speakers
      (96% vs. 85%, P = .04). Because of TS, many reported clarifying their own goals
      of care (61%), talking to their family/friends about ACP (66%), and wanting to
      complete an advance directive (37%). CONCLUSIONS: Most diverse older adults had
      heard of TS and reported that her story activated them to engage in ACP. Media
      stories may provide a powerful opportunity to engage patients in ACP and develop
      public health campaigns.

PMID- 18716850
TI  - Epigenetic regulation of WNT signaling pathway genes in inflammatory bowel
      disease (IBD) associated neoplasia.
AB  - INTRODUCTION: WNT signaling pathway dysregulation is an important event in the
      pathogenesis of colorectal cancer (CRC) with APC mutations seen in more than 80%
      of sporadic CRC. However, such mutations in the WNT signaling pathway genes are
      rare in inflammatory bowel disease (IBD) associated neoplasia (dysplasia and
      cancer). This study examined the role of epigenetic silencing of WNT signaling
      pathway genes in the pathogenesis of IBD-associated neoplasia. METHODS: Paraffin
      embedded tissue samples were obtained and methylation of ten WNT signaling
      pathway genes, including APC1A, APC2, SFRP1, SFRP2, SFRP4, SFRP5, DKK1, DKK3,
      WIF1 and LKB1, was analyzed. Methylation analysis was performed on 41 IBD
      samples, 27 normal colon samples (NCs), and 24 sporadic CRC samples. RESULTS:
      Methylation of WNT signaling pathway genes is a frequent and early event in IBD
      and IBD-associated neoplasia. A progressive increase in the percentage of
      methylated genes in the WNT signaling pathway from NCs (4.2%) to IBD colitis
      (39.7%) to IBD-associated neoplasia (63.4%) was seen (NCs vs. IBD colitis, p <
      0.01; IBD colitis vs. IBD-associated neoplasia, p = 0.01). In the univariate
      logistic regression model, methylation of APC2 (OR 4.7, 95% CI: 1.1-20.63, p =
      0.04), SFRP1 (OR 5.1, 95% CI: 1.1-31.9, p = 0.04), and SFRP2 (OR 5.1, 95% CI: 1.1
      32.3, p = 0.04) was associated with progression from IBD colitis to IBD
      associated neoplasia, while APC1A methylation was borderline significant (OR 4.1,
      95% CI: 0.95-17.5, p = 0.06). In the multivariate logistic regression model,
      methylation of APC1A and APC2 was more likely to be associated with IBD
      associated neoplasia than IBD colitis. (OR APC1A: 6.4, 95% CI: 1.1-37.7 p = 0.04;
      OR APC2 9.1, 95% CI: 1.3-61.7, p = 0.02). SUMMARY: Methylation of the WNT
      signaling genes is an early event seen in patients with IBD colitis and there is
      a progressive increase in methylation of the WNT signaling genes during
      development of IBD-associated neoplasia. Moreover, methylation of APC1A, APC2,
      SFRP1, and SFRP2 appears to mark progression from IBD colitis to IBD-associated
      neoplasia, and these genes may serve as biomarkers for IBD-associated neoplasia.

PMID- 18716851
TI  - The frequency, growth kinetics, and osteogenic/adipogenic differentiation
      properties of canine bone marrow stromal cells.
AB  - Bone marrow stromal cells (BMSCs) have gained considerable attention as a
      potential source for cell transplantation therapies for a variety of diseases due
      to their accessibility, proliferative capacity, and multilineage differentiation
      properties. Canine BMSCs have been shown to contribute to regeneration of osseous
      tissues, but knowledge about their biology is currently limited. In the present
      study, we investigated the frequency of adult canine BMSCs in bone marrow,
      morphological features, growth kinetics, and osteogenic as well as adipogenic
      differentiation properties in vitro. Our data suggest that adult canine bone
      marrow contains approximately one BMSC in every 2.38 x 10(4) bone marrow
      mononucleated cells (0.0042 +/- 0.0019%, n = 5). Primary BMSC cultures consisted
      of morphologically heterogeneous adherent cell populations from which spindle
      shaped cells grew and became the predominant cell type. Growth kinetics patterns
      were dependent on the initial cell seeding densities, resulting in the highest
      fold increase at lower cell density. In the presence of osteogenic and adipogenic
      inducers, primary BMSCs underwent morphological and phenotypic changes
      characteristic of osteogenic and adipogenic differentiation, respectively. This
      study provides insights into basic characterization of adult canine BMSCs.

PMID- 18716853
TI  - Robert R. Oden 1922-2008.

PMID- 18716852
TI  - Effect of Roux-en Y gastric bypass on bone metabolism in patients with morbid
      obesity: Mansoura experiences.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGBP) has been found to be the most
      efficient way to lose weight and maintain the weight loss in morbid obesity.
      However, with the formation of a new stomach and the modification of intestinal
      anatomy, there are significant changes on bone metabolism. The objectives of this
      study were to evaluate effects of weight loss on bone metabolism after Roux-en Y
      gastric bypass in patients with morbid obesity. METHODS: Our study included 70
      patients with morbid obesity; RYGB was done for all patients. Daily postoperative
      oral supplementation with 1,000 mg of calcium and 800 IU of vitamin D was done
      for each patient. Body weight (BW), body mass index (BMI), total body fat, total
      lean tissue mass, bone mineral content (BMC), bone mineral density (BMD), total
      bone area (TBA; using dual energy X-ray absorptiometry), serum calcium,
      parathyroid hormone (PTH), 25-OH vitamin D, 24-h urinary calcium, and bone
      specific alkaline phosphatase (BSAP) were assessed preoperatively and 1 year
      after surgery. RESULTS: In our study, females comprised 70% of cases. The mean
      age was 35+/-8.8 years. One year after RYGB, BW decreased significantly from
      132.8+/-26.5 to 90.3+/-17.3 kg (p=0.001). BMI decreased significantly from 48+/
      7.3 to 32.6+/-4.1 kg/m(2) (p=0.001). BMC decreased significantly from 2,968.6+/
      71.4 to 2,700.8+/-45.4 g (p=0.001). BMD decreased significantly from 1.026+/-0.03
      to 1.22+/-0.015 g/cm(2) (p=0.001). TBA decreased significantly from 2,356.2+/
      35.4 to 2,216.3+/-43.5 cm(2) (p=0.001). Serum calcium, 24-h urinary calcium, and
      BSAP were not significantly decreased while 25-OH vitamin D and PTH were not
      significantly increased after surgery. CONCLUSIONS: From this study, it is shown
      that RYGBP operation gives very good results as regards reduction of body weight
      in morbidly obese patients. Postoperative supplementation with calcium and
      vitamin D partially corrects osteoporosis. Thus, these patients need periodic
      follow-up for BMD, PTH, calcium, serum vitamin D, and markers of bone resorption
      and formation specially postmenopausal female.

PMID- 18716854
TI  - A modeling intervention in heart failure.
AB  - BACKGROUND: Peak oxygen uptake (VO(2)) testing is commonly used to assess chronic
      heart failure (CHF) patients' exercise tolerance. The test requires maximal
      effort; however, many participants have low confidence (self-efficacy) to perform
      optimally. PURPOSE: This randomized controlled trial examined the effectiveness
      of a modeling intervention to increase Peak VO(2) (PVO(2)) and self-efficacy in
      people diagnosed with CHF. METHODS: Twenty participants with a diagnosis of CHF
      were randomized to either an intervention (modeling DVD) or a control group. Both
      groups completed a measure of self-efficacy prior to performing two PVO(2) tests,
      each separated by 7 days. After completing the first test (T1) the intervention
      group watched a 10-min coping model DVD. All participants returned 1 week later
      (T2) to complete identical study procedures. RESULTS: Analysis of covariance
      results showed that compared with the participants in the control group, those
      assigned to the modeling intervention had higher PVO(2) at T2, F (1, 19) = 4.38,
      p = 0.05, eta (2) = 0.21 and self-efficacy, F (1, 19) = 5.80, p < 0.05, eta (2) =
      0.25. Only partial support was found for change in self-efficacy mediating
      treatment outcome (PVO(2)). CONCLUSIONS: Watching a modeling video is associated
      with increased PVO(2) and self-efficacy. These results have implications for
      testing patients in a clinical setting to maximize exercise tolerance test
      results.

PMID- 18716855
TI  - Adaptation to early knee osteoarthritis: the role of risk, resilience, and
      disease severity on pain and physical functioning.
AB  - BACKGROUND: Radiographic joint changes are used to diagnose osteoarthritis;
      however, they alone do not adequately predict who experiences symptoms. PURPOSE:
      To examine psychological risk and resilience factors in combination with an
      objective indicator of disease severity (knee X-rays) to determine what factors
      best account for pain and physical functioning in an early knee osteoarthritis
      (KOA) population. METHODS: Structural equation modeling was used to analyze data
      from 275 men and women with early KOA. RESULTS: Structural equation modeling
      yielded a fair to good fit of the data, suggesting that both risk and resilience
      were important in predicting pain and physical functioning over and above disease
      severity in the expected directions. Resilience's effect on pain was mediated
      through self-efficacy, suggesting that higher self-efficacy was linked to lower
      pain and better physical functioning. CONCLUSIONS: Results provide an integrative
      model of adjustment to early KOA and may be important to the prevention of
      disability in this population.

PMID- 18716856
TI  - The measurement of chronic pain and health-related quality of life following
      inguinal hernia repair: a review of the literature.
AB  - BACKGROUND AND METHODS: This study reviews the existing literature examining
      chronic pain and health-related quality of life (HRQL) outcomes in hernia repair
      studies. A PubMed/Medline and Embase search was carried out to identify relevant
      papers. Studies meeting pre-specified inclusion/exclusion criteria were included
      and fully reviewed. Reference lists were scanned for additional studies. Only
      studies examining chronic (>3 months) post-operative inguinal hernia repair (IHR)
      related pain were included in this review. RESULTS AND CONCLUSIONS: Twenty-three
      studies were identified. The majority of studies used the visual analogue scale
      (VAS) for pain measurement and the Medical Outcomes Study Short-Form 36 (SF-36)
      for the measurement of HRQL. A reasonably consistent picture emerged from the
      literature, with the HRQL domains most often affected by pain (social
      functioning/mental health). Estimates of the prevalence of chronic pain and
      discomfort following IHR vary widely between studies. This is probably a
      reflection of the range of methods used for measuring pain, many of which do not
      have established psychometric properties. Our review suggests that a proportion
      of patients experience chronic pain and discomfort, which has a significant
      impact on HRQL. However, the current instruments used in the evaluation of
      chronic pain after IHR are not comparable and standardisation is required.

PMID- 18716859
TI  - Gd2(MoO4)3:Er(3+) nanophosphors for an enhancement of silicon solar-cell near
      infrared response.
AB  - In an attempt to take full advantage of near-infrared part of the solar spectrum,
      Gd(2)(MoO(4))(3):Er(3+) nanophosphors have been proposed as potential luminescent
      materials to enhance the response of the silicon solar-cell. Upon excitation with
      low-energy near-infrared photons, intense upconverted emissions at 545, 665, 800,
      and 980 nm, for which energies higher than the bandgap of silicon solar-cell,
      have been achieved with conversion efficiencies of 0.12%, 0.05%, 0.83%, and
      1.35%, respectively. Development of nanophosphors for photovoltaic purposes could
      open up an approach in achieving high-efficiency silicon-based solar-cell by
      means of the up-conversion of the sub-bandgap near-infrared part of the solar
      spectrum (E < 1.12 eV) to visible/near-infrared photons.

PMID- 18716858
TI  - Mutant rat strain lacking D-amino-acid oxidase.
AB  - D-amino-acid oxidase (DAO) is known to be associated with schizophrenia. Since
      the expression of DAO gene had been reported to be very low in LEA rats, we
      examined LEA/SENDAI rats in detail. These rats did not have DAO activity, enzyme
      protein or mRNA encoding this enzyme. Sequencing of the 5'-upstream region of the
      DAO gene revealed the deletion of one triplet in the 15 TAA repeats approximately
      700-bp upstream of the transcription start point. A 1.3-kb upstream fragment
      containing the TAA repeats and the transcription start point was inserted into a
      reporter vector and was transfected into COS-1, NRK-52E and CCL-PK1 cells.
      Although the fragments containing 15 or 14 repeats had high promoter activity,
      the fragment containing 13 repeats had very weak activity. Electrophoretic
      mobility-shift assays showed that the nuclear extracts from COS-1 and COS-7 cells
      had proteins that bound to the oligonucleotides containing the TAA repeats. These
      results suggest that the TAA repeats are important for expression of the DAO
      gene. The LEA/SENDAI rats lacking DAO would be a useful tool for the
      investigations aimed at the elucidation of the relationships between this
      flavoenzyme and schizophrenia.

PMID- 18716860
TI  - Exploring the nature of photo-damage in two-photon excitation by fluorescence
      intensity modulation.
AB  - We investigate the relative photo-damage effects during one- and two-photon
      excitations and demonstrate that there exist fundamental differences in the
      damage induced by a high repetition rate laser as compared to that of a CW laser.
      This difference is evident from the degree of enhanced fluorescence intensity
      achieved by blanking the excitation with an optical chopper. Such an enhancement
      in fluorescence intensity provides better signal-to-noise ratio that could have
      immediate applications in multiphoton imaging of live specimens.

PMID- 18716861
TI  - T regulatory cells in autoimmune diabetes: past challenges, future prospects.
AB  - INTRODUCTION: Accumulating evidence suggests that defective regulation is an
      essential underlying cause of autoimmunity. The development of type 1 diabetes in
      the NOD mouse strain it is a complex process that depends on a fine balance
      between pathogenic and regulatory pathways. DISCUSSION: We have utilized a series
      of transgenic and knockout mice to determine the relative importance of
      regulatory T cells and negative regulatory receptors on the development and
      progression of type 1 diabetes. CONCLUSION: This review will focus on the origins
      and function of Treg in peripheral self-tolerance. We will summarize the role of
      Treg in preventing autoimmune diseases, with a particular focus on Type 1
      Diabetes (T1D), and discuss the prospects for Treg-based therapies for autoimmune
      diseases.

PMID- 18716862
TI  - Detection of breast cancer metastasis in sentinel lymph nodes using intra
      operative real time GeneSearch BLN Assay in the operating room: results of the
      Cardiff study.
AB  - BACKGROUND: Intra-operative assessment is not routinely performed in the UK due
      to poor sensitivity of available methods and overburdened pathology resources. We
      conducted a prospective clinical feasibility study of the GeneSearch Breast Lymph
      Node (BLN) Assay (Veridex, LLC, Warren, NJ) to confirm its potential usefulness
      within the UK healthcare system. METHODS: In the assay 50% of the lymph node was
      processed to detect the presence of cytokeratin-19 and mammaglobin mRNA. The
      assay was calibrated to detect metastases >0.2 mm. Assay results were compared to
      H&E performed on each face of approximately 2 mm alternating node slabs and 3
      additional sections cut at approximately 150 microm interval from each face of
      the node slab. RESULTS: 124 sentinel lymph nodes were removed from 82 breast
      cancer patients. The assay correctly identified all 6 patients with sentinel node
      macrometastases (>2.0 mm), and 2 of 3 patients with sentinel node micrometastases
      (0.2-2.0 mm). Sentinel lymph nodes in 4 patients were assay positive but
      histology negative. Two of these four patients had isolated tumor cells seen by
      histology. The overall concordance with histology was 93.9% (77/82), with
      sensitivity of 88.9% (8/9, 95% CI 56.5-98%), specificity of 94.6% (69/73, 95% CI
      86.7-97.8%), positive predictive value of 66.7% (8/12, 95% CI 39.1-86.2%) and
      negative predictive value of 98.6% (69/70, 95% CI 92.3-99.7%). The assay was
      performed in a median time of 32 min (range 26-69 min). CONCLUSION: Intra
      operative assessment of sentinel lymph node can be performed rapidly and
      accurately using the GeneSearch BLN Assay.

PMID- 18716863
TI  - The role and mechanism of the up-regulation of fibrinolytic activity in painful
      peripheral nerve injury.
AB  - Peripheral nerve injury is followed by Wallerians degeneration (WD) and
      degradation and regeneration of the extracellular matrix (ECM) are very important
      events in these processes. We tested fibrinolytic activities and the expression
      level of tPA and uPA levels in chronic constriction injury (CCI) model. The
      presented data demonstrates that in the injury nerve of CCI model, the
      fibrinolytic activities is upregulated and main caused by the upregulation of tPA
      expression. We also find that the activities of tPA and MMP-9 are co-upregulated
      post-CCI, both at CCI site and proximal site. These results indicate that tPA
      activity may regulate the MMP-9 activity in injury nerve post-CCI.

PMID- 18716864
TI  - Lactate contributes to ammonia-mediated astroglial dysfunction during
      hyperammonemia.
AB  - Even though ammonia is considered to underlie nervous system symptoms of
      dysfunction during hyperammonemia, lactate, which increases as a metabolic
      consequence of high ammonia levels, might also be a contributing factor. The data
      presented here show that NH4Cl (5 mM) mediates astroglial cell swelling, and that
      treatment with NH4Cl or lactate (25 mM) causes rearrangements of actin filaments
      and reduces astroglial glutamate uptake capacity. Co-application with BaCl2,
      which blocks astroglial uptake of NH4+, prevents NH4Cl-mediated cell swelling and
      rearrangement of actin filaments, but does not reduce NH4Cl-induced glutamate
      uptake capacity inhibition. Neither NH4Cl nor lactate affected glutamate uptake
      or protein expression in microglial cultures, indicating that astroglial cells
      are more susceptible to the neurotoxic affects of ammonia. Our results suggest
      that ammonium underlies brain edema, but that lactate can contribute to some of
      the cellular dysfunctions associated with elevated cerebral levels of ammonia.

PMID- 18716865
TI  - HCV and TTV co-infection in Turin, Italy.

PMID- 18716867
TI  - Clarifying the relationship between ABO/Rhesus blood group antigens and upper
      gastrointestinal bleeding.
AB  - BACKGROUND AND AIM: The relationship between blood group antigens and peptic
      ulcer disease has been widely evaluated in the past. Data concerning the same
      association with upper gastrointestinal bleeding are very limited. We aimed to
      evaluate this association and we thought it was worthwhile to try to determine
      whether these components take some part in this complication. METHODS: The study
      population consisted of 1,098 adults (364 patients and 734 volunteer blood donors
      as controls). Demographic features, comorbid illnesses, and use of
      aspirin/nonsteroidal anti-inflammatory drugs (NSAIDs) were recorded. Blood groups
      were examined by gel centrifugation method. We included only patients with
      bleeding from peptic ulcer disease and erosive gastropathy. Ulcers were
      classified by using Forrest's classification system in terms of rebleeding risk.
      Helicobacter pylori was examined by histology. RESULTS: The gender distribution
      was similar in both groups. The ABO blood group phenotype distribution in
      patients and controls (respectively) was as follows: 46.2% versus 34.9% for group
      O, 32.4% versus 39.5% for group A, 15.7% versus 18.4% for group B, and 5.8%
      versus 7.2% for group AB. Blood group O was found to have higher frequency in the
      patient group than in the control group (P=0.004). Rh positivity was also higher
      in patients than in controls (P=0.007). H. pylori positivity was similar between
      blood groups among patients. The rebleeding and mortality rates between blood
      groups were also similar. CONCLUSION: ABO blood group O had an important role in
      patients with upper gastrointestinal bleeding. The impact of blood group on
      rebleeding and mortality may be a focus for further studies.

PMID- 18716866
TI  - Spontaneous regression of hepatocellular carcinoma: three case reports and a
      categorized review of the literature.

PMID- 18716868
TI  - Development, validation, and applicability of a symptoms questionnaire for
      lactose malabsorption screening.
AB  - Lactase deficiency has a high prevalence worldwide. Thus, a valid symptom scale
      would be a useful tool for identifying patients with lactose malabsorption.
      OBJECTIVE: To develop, validate, and apply a symptoms questionnaire on lactose
      malabsorption to identify lactose malabsorbers diagnosed with the gold-standard
      hydrogen breath test. METHODS: In the first part of the study, 292 patients
      completed a questionnaire at the end of a 50-g lactose breath test. The
      questionnaire included five items (diarrhea, abdominal cramping, vomiting,
      audible bowel sounds, and flatulence or gas) scored on a 10-cm visual analogue
      scale. In the second part of the study, 171 patients completed the questionnaire
      twice: first, according to their opinion when consuming dairy products at home
      and second, after a 50-g lactose breath test. Patients were grouped as absorbers
      or malabsorbers according to the result of the breath test. RESULTS: Diarrhea,
      abdominal cramping, and flatulence were scored significantly higher in
      malabsorbers than in absorbers. Total score of the symptomatic questionnaire was
      significantly higher in malabsorbers (17.5 versus 3.0, P<0.01). According to
      receiver operator characteristics (ROC) analysis, the most discriminant cut-off
      of the total score to identify lactose malabsorption was 6.5 (sensitivity 0.75,
      specificity 0.67). In 58 malabsorbers the effect size of the questionnaire to
      determine sensitivity to change was 1.32. In the second part of the study,
      scoring of the home questionnaire was higher than after the lactose-breath test.
      The lactose malabsorbers rate was higher according to the home questionnaire than
      after the lactose breath test (72% versus 52%). The home questionnaire had
      excellent sensitivity (0.82) but low specificity (0.35). CONCLUSION: We developed
      and validated a five-item symptoms questionnaire for lactose malabsorption. This
      is a valid test that permits patients with a total score lower than 7 to be
      excluded from future studies.

PMID- 18716869
TI  - Pulmonary nodules as an extra-intestinal manifestation of inflammatory bowel
      disease: a case series and review of the literature.

PMID- 18716870
TI  - The association between the survivin C-31G polymorphism and gastric cancer risk
      in a Chinese population.
AB  - INTRODUCTION: The C-31G polymorphism in the survivin promoter could de-repress
      the cell-cycle-dependent transcription of the human survivin gene, resulting in
      overexpression of survivin. This survivin mutation has only been studied on
      cervical carcinoma. However, no study has ever been conducted to evaluate the
      effect of the polymorphism on other cancers, including gastric cancer. METHODS:
      In this hospital-based, case-control study, we investigated the association
      between the survivin C-31G polymorphism and risk of gastric cancer in a Chinese
      population using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) protocols. RESULTS: No statistically significant
      association was observed between gastric cancer risk and the variant genotype (GG
      + GC). However, the variant genotype (GG + GC) was either associated with risk of
      distal gastric cancer (odds ratios=0.50, 95% confidence interval=0.30-0.83) or
      with risk of well-differentiated tumor (odds ratios=0.46, 95% confidence
      interval=0.22-0.97). CONCLUSION: Our results demonstrate that the survivin C-31G
      polymorphism may be involved in distal gastric carcinogenesis and tumor
      differentiation in a Chinese population.

PMID- 18716871
TI  - Association of visceral fat accumulation and adiponectin levels with colorectal
      neoplasia.
AB  - PURPOSE: There are few studies addressing the association between measured values
      of visceral fat accumulation (VFA), adiponectin, and colorectal neoplasia. Our
      purpose is to investigate the association of VFA and serum adiponectin levels
      with colorectal adenoma and carcinoma patients. For this purpose, 54 patients
      with colorectal adenoma and carcinoma, diagnosed by colonoscopic evaluation, and
      50 healthy control subjects were included. Patients were subjected to measurement
      of VFA and adiponectin level and calculation of insulin resistance. RESULTS:
      Patients with colorectal carcinoma had lower plasma adiponectin levels compared
      with controls. VFA level did not differ between patients and controls.
      Adiponectin level was found to be uncorrelated with VFA in the colorectal cancer
      and adenoma group. No correlation was found between insulin resistance and plasma
      adiponectin level and VFA. CONCLUSION: Our findings suggest that decreased plasma
      adiponectin level may be a factor involved in the development of colon cancer or
      a secondary effect of the metabolic derangements in colorectal cancer.

PMID- 18716872
TI  - Effects of N-acetylcysteine plus mesalamine on prostaglandin synthesis and nitric
      oxide generation in TNBS-induced colitis in rats.
AB  - The aim of the present studies was to examine mechanisms by which the rectally
      administered combination of N-acetylcysteine (NAC) plus mesalamine (5-ASA)
      affects inducers of inflammation to promote mucosal healing and reduce tissue
      inflammation in chemically (trinitrobenzene sulfonic acid, TNBS) induced colitis
      in rats. Experimental findings demonstrate that dual therapy with NAC plus 5-ASA
      was superior to individual agents in reducing histological measures of colitis.
      NAC alone and in combination with 5-ASA suppressed COX2 gene expression and
      prostaglandin E(2) (PGE(2)) levels to control values. Furthermore, NAC plus 5-ASA
      reduced nitrate generation, an expression of inducible nitric oxide synthase
      (iNOS) activity, to basal levels and these results were significantly lower than
      those observed with either NAC or 5-ASA alone. In conclusion, these results
      indicate that NAC plus 5-ASA exerts therapeutic benefit, in part by countering
      the actions of PGE(2) and the deleterious effects of oxidative and nitrosative
      stress induced by TNBS colitis.

PMID- 18716873
TI  - Prevalence of celiac disease in Turkish children with autoimmune thyroiditis.
AB  - The close association between celiac disease (CD) and autoimmune disorders is
      well documented in adult and pediatric patients. The aim of this study is to
      determine the prevalence of CD in Turkish children with autoimmune thyroiditis
      (AT). Sera from 101 children with AT (11 boys and 90 girls, from 2 to 18 years of
      age; mean age 12.28 +/- 3.26 years) and 103 healthy children (46 boys and 57
      girls, from 3.5 to 17 years of age; mean age 12.18 +/- 3.11 years) were screened
      for CD using the IgA anti-tissue transglutaminase (IgA anti-tTG) antibody and
      total serum IgA. Small intestinal biopsy was offered to all antibody-positive
      patients. IgA anti-tTG was positive in eight children (7.9%) with AT. None of the
      serum samples of healthy children were positive for IgA anti-tTG antibody.
      Selective IgA deficiency was not detected in patients or controls. Intestinal
      biopsy was accepted by seven patients. In five patients (4.9%), subtotal villous
      atrophy was found. These findings indicate that the prevalence of CD is higher in
      Turkish children with AT than in healthy controls. Routine screening for CD
      should be performed in children with AT.

PMID- 18716874
TI  - Red cell distribution width for assessment of activity of inflammatory bowel
      disease.
AB  - BACKGROUND: Impaired iron absorption or increased loss of iron was found to
      correlate with disease activity and markers of inflammation in inflammatory bowel
      disease (IBD). Red cell distribution width (RDW) could be a reliable index of
      anisocytosis with the highest sensitivity to iron deficiency. AIM: The importance
      of RDW in assessment of IBD disease activity is unknown. In this study, we aimed
      to determine if RDW could be useful in detecting active disease in patients with
      IBD. MATERIALS AND METHODS: A total of 74 patients with ulcerative colitis (UC)
      and 22 patients with Crohn's disease (CD) formed the study group with 20 age- and
      sex-matched healthy volunteers as the control group. CD activity index higher
      than 150 in patients with CD was considered to indicate active disease. Patients
      with moderate and severe disease according to the Truelove-Witts scale were
      accepted as having active UC. In addition to RDW, serum C-reactive protein (CRP)
      and fibrinogen levels, erythrocyte sedimentation rates (ESR), leukocyte, and
      platelet counts were measured. RESULTS: Fourteen (63.6%) of the patients with CD
      and 43 (58.1%) of the patients with UC had active disease. RDW, fibrinogen, CRP,
      ESR, and platelet counts were all significantly elevated in patients having
      active IBD compared with those without active disease and controls (P < 0.05).
      The study subjects were further classified into two subgroups: cases with active
      and inactive UC and those with active and inactive CD. A subgroup analysis
      indicated that for an RDW cutoff of 14, the sensitivity for detecting active UC
      was 88% and the specificity was 71% (area under curve [AUC] 0.81, P = 0.0001).
      RDW was the most sensitive and specific parameter indicating active UC. However,
      the same was not true for CD since CRP at a cutoff of 0.54 mg/dl showed a
      sensitivity of 92% and a specificity of 63% (AUC 0.92, P = 0.001), whereas RDW at
      a cutoff of 14.1 showed 78% sensitivity and 63% specificity to detect active CD.
      CONCLUSION: Among the laboratory tests investigated, including fibrinogen, CRP,
      ESR, and platelet counts, receiver operating characteristic (ROC) curve analysis
      indicated RDW to be the most significant indicator of active UC. For CD, CRP was
      an important marker of active disease.

PMID- 18716875
TI  - Bridge treatments of hepatocellular carcinoma in cirrhotic patients submitted to
      liver transplantation.

PMID- 18716877
TI  - Benign small bowel thickening and lymphadenopathy: a manifestation of celiac
      disease.

PMID- 18716878
TI  - MCM2 and MCM5 as prognostic markers in colon cancer: a worthwhile approach.

PMID- 18716876
TI  - Pleiotrophin expression in human pancreatic cancer and its correlation with
      clinicopathological features, perineural invasion, and prognosis.
AB  - Pleiotrophin (PTN), a heparin-binding growth factor also known as neurite growth
      promoting factor, exhibits several properties related with tumor development. PTN
      and its receptor, N-syndecan, may play a very important role in tumor growth and
      neural invasion of pancreatic cancer. We investigated PTN and N-syndecan protein
      levels in 38 patients with pancreatic cancer by immunohistochemistry, and
      analyzed for its correlation with clinicopathological features, perineural
      invasion, and prognosis. The results showed that PTN and N-syndecan proteins were
      found in 24 (63.2%) and 22 (57.9%) specimens, respectively. PTN and N-syndecan
      expressions were associated with perineural invasion (P = 0.016 and P = 0.029,
      respectively). High PTN expression was closely related to an advanced TNM stage
      (P = 0.007), lymph node metastasis (P = 0.040), and decreased postoperative
      survival at 3 years (50.0% versus 20.8%, respectively; P = 0.001). We conclude
      that high expression of PTN combined with N-syndecan may contribute to the
      increased perineural invasion and poor prognosis of pancreatic cancer.

PMID- 18716879
TI  - Assessment of pre-gastroscopy fasting period using ultrasonography.
AB  - Discomfort is frequent in patients undergoing esophagogastroduodenoscopy who are
      routinely recommended to abstain at least for 6 h from liquid or solid food prior
      to the procedure. We investigated the minimal period of time required for the
      stomach to clear fluids in order to define a safe minimal pre-endoscopy fasting
      period. Gastric emptying was sonographically assessed in 54 patients by
      measurement of the antrum surface area prior to, immediately after, and 30, 60,
      and 90 min after ingestion of 300 ml water and water containing 75 g glucose or
      apple juice. Esophagogastroduodenoscopy was performed subsequently. Ingestion of
      water required 1 h for complete clearance. Three hundred milliliters glucose
      solution and apple juice were cleared more slowly, 90 min after drinking.
      Ingestion of water or glucose solution prior to esophagogastroduodenoscopy in
      patients without a history of gastric emptying dysfunction is safe when observing
      a 90 min latency period and might prevent discomfort.

PMID- 18716880
TI  - The 3'UTR NFKBIA variant is associated with extensive colitis in Hungarian IBD
      patients.
AB  - PURPOSE: In previous studies the NFKBIA 3'UTR (untranslated region) AA genotype
      was associated with Crohn's disease (CD), while the NFKB1-94ins/delATTG mutation
      increased the risk for ulcerative colitis (UC). The aim of our study was to
      investigate these two polymorphisms and patients' response to medical therapy
      and/or disease phenotype in Hungarian inflammatory bowel disease (IBD) patients.
      METHODS: NFKBIA 3'UTR- and NFKB1-94ins/delATTG polymorphisms were investigated in
      415 unrelated IBD patients (CD: 266 patients, mean age 35.2 +/- 12.1 years,
      duration 8.7 +/- 7.5 years; UC patients: 149, mean age 44.4 +/- 15.4 years,
      duration 10.7 +/- 8.9 years) and 149 controls by PCR-restriction fragment length
      polymorphism (RFLP) analysis. Detailed clinical phenotypes were determined by
      reviewing the medical charts. RESULTS: The NFKBIA 3'UTR and NFKB1-94ins/delATTG
      genotypes and allele frequencies were not significantly different among IBD and
      controls. In patients with UC, the 3'UTR GG genotype was associated with
      extensive colitis (55.3 vs. 29.4%, odds ratio 2.97, 95% confidence interval 1.45
      6.08). The presence of variant alleles did not predict response to steroids,
      infliximab, or need for surgery. CONCLUSIONS: The NFKBIA 3'UTR GG genotype was
      associated with an increased risk for extensive colitis in Hungarian patients. In
      contrast, variant alleles did not predict response to medical therapy or need for
      surgery.

PMID- 18716881
TI  - Lap4, a vacuolar aminopeptidase I, is involved in cadmium-glutathione metabolism.
AB  - In Saccharomyces cerevisiae, accumulation of cadmium-glutathione complex in
      cytoplasm inhibits cadmium absorption, glutathione transferase 2 is required for
      the formation of the complex and the vacuolar gamma-glutamyl transferase
      participates of the first step of glutathione degradation. Here, we proposed that
      Lap4, a vacuolar amino peptidase, is involved in glutathione catabolism under
      cadmium stress. Saccharomyces cerevisiae cells deficient in Lap4 absorbed almost
      3-fold as much cadmium as the wild-type strain (wt), probably due to the lower
      rate of cadmium-glutathione complex synthesis in the cytoplasm. In wt, but not in
      lap4 strain, the oxidized/reduced GSH ratio and the Gtt activity increased in
      response to cadmium, confirming that the mutant is deficient in the synthesis of
      the complex probably because the degradation of vacuolar glutathione is impaired.
      Thus, under cadmium stress, Lap4 and gamma-glutamyl transferase seem to work
      together to assure an efficient glutathione turnover stored in the vacuole.

PMID- 18716882
TI  - Silencing of a BYPASS1 homolog results in root-independent pleiotrophic
      developmental defects in Nicotiana benthamiana.
AB  - The Arabidopsis bypass1 mutant (bps1) exhibits defective shoot and root growth
      that is associated with constitutive production of a root-derived carotenoid
      related signal (Van Norman et al., Curr Biol 14:1739-1746, 2004). Since the
      identity of the signal and the function of BPS1 are still unknown, we
      investigated effects of BPS1 depletion in Nicotiana benthamiana to elucidate BPS1
      function in plant growth and development. The predicted protein of NbBPS1, a BPS1
      homolog of N. benthamiana, contains a central transmembrane domain, and a
      NbBPS1:GFP fusion protein was mainly associated with the endoplasmic reticulum.
      Virus-induced gene silencing (VIGS) of NbBPS1 resulted in pleiotrophic
      phenotypes, including growth retardation and abnormal leaf development. At the
      cellular level, the plants exhibited hyperproliferation of the cambial cells and
      defective xylem differentiation during stem vascular development. Hyperactivity
      of the cambium was associated with an elevated auxin and cytokinin response. In
      contrast, the leaves had reduced numbers of cells with increased cell size and
      elevated endoreduplication. Cell death in NbBPS1 VIGS leaves started with vacuole
      collapse, followed by degeneration of the organelles. Interestingly, these
      phenotypes were mainly caused by silencing of NbBPS1 in the aerial parts of the
      plants, different from the case of the Arabidopsis bps1 mutant. These results
      suggest that NbBPS1 plays a role in the control of cell division and
      differentiation in the cambium of N. benthamiana, and BPS homologs may have a
      diverse function in different tissues and in different species.

PMID- 18716883
TI  - Developments in statistical analysis in quantitative genetics.
AB  - A remarkable research impetus has taken place in statistical genetics since the
      last World Conference. This has been stimulated by breakthroughs in molecular
      genetics, automated data-recording devices and computer-intensive statistical
      methods. The latter were revolutionized by the bootstrap and by Markov chain
      Monte Carlo (McMC). In this overview a number of specific areas are chosen to
      illustrate the enormous flexibility that McMC has provided for fitting models and
      exploring features of data that were previously inaccessible. The selected areas
      are inferences of the trajectories over time of genetic means and variances,
      models for the analysis of categorical and count data, the statistical genetics
      of a model postulating that environmental variance is partly under genetic
      control, and a short discussion of models that incorporate massive genetic marker
      information. We provide an overview of the application of McMC to study model
      fit, and finally, a discussion is presented on the development of efficient McMC
      updating schemes for non-standard models.

PMID- 18716884
TI  - Maternal unemployment: an indicator of spontaneous preterm delivery risk.
AB  - The aim of this study was to assess the association between maternal employment
      and preterm delivery. A nationwide case-control study was conducted in 25
      Portuguese public maternities. During a 4-month period, 769 consecutive single
      spontaneous preterm (<37 gestation weeks) live births and 1,053 term singleton
      babies born immediately after each preterm, were evaluated. Information was
      obtained by attending physicians using a questionnaire, with special emphasis on
      maternal work characterization. Logistic regression odds ratios (OR) were
      adjusted for maternal age, marital status, education and obstetrical
      characteristics. Women entering pregnancy while unemployed presented a
      significantly increased risk of spontaneous preterm delivery (OR=1.5; 95%
      confidence interval (CI) 1.18-1.88). Weekly duration of work (<40 versus >or=40
      h) had no significant effect on the occurrence of spontaneous preterm (OR=1.2;
      95% CI 0.88-1.54). Unemployed women presented a significant increase in the risk
      of preterm delivery.

PMID- 18716885
TI  - Is it possible to estimate the incidence of breast cancer from medico
      administrative databases?
AB  - One approach to estimate cancer incidence in the French Departements is to
      quantify the relationship between data in cancer registries and data obtained
      from the PMSI (Programme de Medicalisation des Systemes d'Information Medicale).
      This relationship may then be used in Departements without registries to infer
      the incidence from local PMSI data. We present here some methodological solutions
      to apply this approach. Data on invasive breast cancer for 2002 were obtained
      from 12 Departemental registries. The number of hospital stays was obtained from
      the National PMSI using two different algorithms based on the main diagnosis only
      (Algorithm 1) or on that diagnosis associated to a mention of "resection"
      (Algorithm 2). Considering registry data as gold standard, a calibration approach
      was used to model the ratio of the number of hospital stays to the number of
      incident cases. In Departements with registries, validation of the predictions
      was done through cross-validation. In Departements without registries, validation
      was done through a study of homogeneity of the mean number of hospital stays per
      patient. Cross-validation showed that the estimates predicted by the model were
      true with data extracted by Algorithm 1 but not by Algorithm 2. However, with
      Algorithm 1, there was an important heterogeneity between French Departements as
      to the mean number of hospital stays per patient, which had an important impact
      on the estimations. In the near future, the method will allow using medico
      administrative data (after calibration with registry data) to estimate
      Departemental incidence of selected cancers.

PMID- 18716886
TI  - Hypophysectomy and hormonal therapy modulate mK1-immunoreactive duct cells in the
      mice sublingual glands.
AB  - The immunocytochemical localization of a true tissue kallikrein, mK1, in mouse
      sublingual glands (SLGs) was examined following hypophysectomy and hormonal
      replacement therapy. In the glands of intact mice (14 weeks of age), mK1 was
      detected in the striated ducts (SDs). Full-fledged granular cells were scattered
      in the SDs of male mice (but not in those of female mice), showing a cellular
      mosaic distribution of mK1 with some being positive and others being negative.
      mK1 was also detected in transitional-type granular cells, though the secretory
      granules were too small and scarce to be visible by a light microscopy.
      Hypophysectomy in male mice resulted in the atrophy and loss of secretory
      granules in many SD cells. Granulation recovered after the repeated injection of
      5alpha-dihydrotestosterone (DHT), 3,5,3'-triiodo-L: thyronine (T3), and
      dexamethasone (Dex), given either alone or in combination to the
      hypophysectomized mice. The concomitant injection of DHT and T3, with or without
      Dex, resulted in the reappearance of the full-fledged granular cells, only some
      of which were mK1-positive. Electron microscopy revealed mK1 to be present
      exclusively in the secretory granules of these mK1-positive cells, and no
      ultrastructural differences were observed between mK1-positive and mK1-negative
      full-fledged granular cells. These results show that the differentiation of the
      granular cell phenotype in the mouse SLG duct system requires the concomitant
      action of androgen and thyroid hormone and retards mK1 synthesis.

PMID- 18716887
TI  - Investigation of pulse transit time characteristics during single and recurrent
      obstructive respiratory events.
AB  - Conventional overnight polysomnography (PSG) used to determine the respiratory
      behaviour during sleep can be a complex and expensive procedure. Pulse transit
      time analysis (PTT) has shown potential to detect obstructive apnoeic and
      hypopnoeic events (OE) in adults. Due to abnormalities in central ventilatory
      control, recurring OE may occur. This study was undertaken to determine the
      potential of PTT to differentiate responses during upper airway obstruction in
      the paediatric population. This preliminary study included 11 children (10 male;
      aged 7.5 +/- 3.8 year) recruited to investigate PTT trend during single and
      recurrent OE. PTT measurements were evaluated against the corresponding PSG
      results pre-scored by two blinded observers. A total of 110 valid OE (47 single
      and 63 recurrent) were observed during these PSG studies. There were distinct PTT
      responses observed for these two types of OE with respect to those of tidal
      breathing (P < 0.05). For the tidal breathing events, the mean absolute standard
      deviation (SD) and maximal percentage (%) decrease (MAX) were 7.71 ms and 3.88%
      respectively. For the recurrent OE, the absolute SD, SD (%) and MAX were 52.21
      ms, 8.52% and 55.08% accordingly while for the single OE, the absolute SD, SD (%)
      and MAX were 12.23 ms, 5.27% and 13.56% respectively. The findings herein can
      suggest that PTT can be a valuable clinical tool in the paediatric respiratory
      sleep studies.

PMID- 18716888
TI  - Toxicity of landfill leachate to sea urchin development with a focus on ammonia.
AB  - Sea urchin gametes and embryos serve as a model system to evaluate toxicity in
      the marine environment. In this study, the toxicity of complex chemical mixtures
      in leachate samples to sea urchin development was examined with a focus on
      ammonia, which was the main contaminant of concern in most samples. Two rapid
      tests, the submitochondrial particle function and bacterial luminescence tests,
      were also used. Ammonia is highly toxic to sea urchin embryos with an EC50 of 1.3
      mg l(-1) for the embryos of the Australian sea urchin Heliocidaris tuberculata.
      Leachate ammonia levels were well above these EC50 concentrations. To assess the
      contribution of ammonia to leachate toxicity in sea urchin development, we
      compared the predicted toxic units (PTU) and observed toxic units (OTU) for
      ammonia for each sample. The PTU/OTU comparison revealed that the sensitivity of
      the sea urchin embryos to ammonia were altered (enhanced or decreased) by other
      chemicals in the leachates. This result emphasises the need for parallel chemical
      analyses and a suite bioassays for evaluating the toxicity of complex and
      variable chemical mixtures.

PMID- 18716889
TI  - An investigation on the pollution status of holy aquifers of Rameswaram, Tamil
      Nadu, India.
AB  - The Study area is the sacred Ramanathasamy temple and selected for the
      characterization of physico-chemical parameters viz., pH, EC, TDS, Salinity, TA,
      TH, Ca( + 2), Mg( + 2), Chloride and Fluoride for 22 groundwater samples and the
      impact of pre- and post-monsoon on the groundwater quality was also studied. The
      study area is well known for the chronic fresh water shortage and the locals
      depend mostly on springs for their fresh water needs. The Water Quality Index
      (WQI) computed shows the transfer of samples under unacceptable quality to
      acceptable quality. The Langelier Saturation Index (LSI) reflected that majority
      of the samples have the tendency to form scale. The Karl Pearson correlation
      matrix has approved the maximum relationship of calcium and chloride with respect
      to the total dissolved solids (TDS). It is interesting to conclude that the
      groundwater in the study area has very hard nature, especially of non-carbonate
      type.

PMID- 18716890
TI  - An overview of functional and stereological evaluation of spermatogenesis and
      germ cell transplantation in fish.
AB  - Although there are almost thirty-thousand species of fish living in a great
      variety of habitats and utilizing vast reproductive strategies, our knowledge of
      morphofunctional and quantitative aspects of testis structure and spermatogenesis
      is still incipient for this group of vertebrates. In this review, we discuss
      aspects that are important to better understanding of testis structure and
      function, and of the development of germ cells (GC) during spermatogenesis. To
      achieve this, we have recently completed a number of studies presenting
      morphometric and functional data related to the numbers of GC and Sertoli cells
      (SC) per each type of spermatogenic cyst, the number of spermatogonial
      generations, the SC efficiency, and the magnitude of GC loss that normally occurs
      during spermatogenesis. We also investigated SC proliferation and the
      relationship of this important event to early spermatogenic cysts. The available
      data strongly suggest that SC proliferation in sexually mature tilapia is the
      primary factor responsible for the increase in testis size and for determination
      of the magnitude of sperm production. The influence of temperature on the
      duration of spermatogenesis in tilapia was also evaluated and we have used this
      knowledge to deplete endogenous spermatogenesis in this teleost, in order to
      develop an experimental system for GC transplantation. This exciting technique
      results in new possibilities for investigation of spermatogenesis and
      spermatogonial stem cell biology, creating also an entirely new and promising
      scenario in biotechnology-transgenic animal production and the preservation of
      the genetic stocks of valuable animals or endangered species.

PMID- 18716891
TI  - Elbow dysplasia and lesions of the medial coronoid process: correlation between
      tomographic and arthroscopic findings in thirty cases.

PMID- 18716892
TI  - Binding of estrogen receptor alpha promoter to nuclear proteins of mouse cerebral
      cortex: effect of age, sex, and gonadal steroids.
AB  - Majority of estrogen actions in the brain are mediated by estrogen receptor (ER)
      alpha which in turn is regulated by several factors like circulating levels of
      gonadal steroid hormones 17beta-estradiol and testosterone, sex and age of the
      organism. The expression of ERalpha is regulated through interaction between cis
      elements of its promoter and proteins present in the nuclei. Here, we have used
      electrophoretic mobility shift assay (EMSA) to analyze the effect of age, sex,
      17beta-estradiol, and testosterone on the binding of ERalpha promoter (-91 to +46
      bp) to nuclear proteins from the mouse cerebral cortex. EMSA revealed the
      formation of three specific complexes in all groups. However, the intensity of
      these complexes varied as a function of age, sex and treatment with 17beta
      estradiol and testosterone. Nuclear proteins from the cerebral cortex of both
      sexes showed reduced binding with promoter fragment in old mice. Further,
      competition analysis indicated stronger binding in females than males of both
      ages. The extent of binding was reduced by 17beta-estradiol and testosterone
      treatment in both ages and sexes. Thus, these findings demonstrate differential
      binding of nuclear proteins to mouse ERalpha promoter which may account for
      different functions of estrogen in the brain.

PMID- 18716893
TI  - Chinese herbal medicine for Mild Cognitive Impairment and Age Associated Memory
      Impairment: a review of randomised controlled trials.
AB  - This review assesses the effectiveness and safety of Chinese herbal medicines
      (CHM) for Mild Cognitive Impairment (MCI) and Age Associated Memory Impairment
      (AAMI). Electronic searches of English and Chinese databases and hand searches of
      Chinese journal holdings were conducted. Randomised controlled trials comparing
      orally administered CHM with placebo, no intervention or other therapy were
      considered. Ginkgo biloba was excluded. Ten trials met inclusion criteria. Eight
      different CHM were investigated. Methodological quality was assessed using the
      Jadad scale and five studies scored three or above. Two studies compared CHM with
      placebo and eight with another intervention. This review found an overall benefit
      on some outcome measures for the eight CHMs involved in the 10 RCTs but
      methodological and data reporting issues were evident. Meta-analysis of three
      studies found the effects of the CHMs were at least equivalent to piracetam on
      Mini-Mental State Examination (MMSE) scores. No severe adverse events were
      reported.

PMID- 18716894
TI  - Structures and functions of the extrinsic proteins of photosystem II from
      different species.
AB  - This minireview presents a summary of information available on the variety and
      binding properties of extrinsic proteins that form the oxygen-evolving complex of
      photosystem II (PSII) of cyanobacteria, red alga, diatom, green alga, euglena,
      and higher plants. In addition, the structure and function of extrinsic PsbO,
      PsbV, and PsbU proteins are summarized based on the crystal structure of
      thermophilic cyanobacterial PSII together with biochemical and genetic studies
      from various organisms.

PMID- 18716895
TI  - Use of CHROMagar in the differentiation of common species of Candida.
AB  - CHROMagar has been reported to be useful for the rapid and accurate
      identification of Candida species. We tested 135 isolates of Candida species
      isolated from oropharyngeal candidiasis in HIV patients and found that it was
      useful in the presumptive identification of Candida albicans and Candida krusei.
      Occasional strains of C. tropicalis produced colonies with a greenish tinge
      making it difficult to differentiate from C. albicans.

PMID- 18716896
TI  - PARP-1 Val762Ala polymorphism, CagA+ H. pylori infection and risk for gastric
      cancer in Han Chinese population.
AB  - INTRODUCTION: PARP-1 plays important role in the BER (base excision repair) and
      maintenance of genomic integrity. Previous study found the Val762Ala genetic
      variant in the PARP-1 gene contributed to susceptibility of some cancers and
      decreased PARP-1 enzyme activity in response to oxidative damage. Helicobacter
      pylori (H. pylori) infection was thought to be one of the major causes of gastric
      cancer. In this study, we investigated the association between the PARP-1
      Val762Ala polymorphism, CagA(+) H. pylori infection, and the risk for gastric
      cancer. METHODS: This hospital-based, case-control study was performed involving
      556 individuals (236 cases with gastric cancer and 320 controls without evidence
      of neoplasm and gastrointestinal disease) using a PCR-RFLP method. Chi-square
      test and logistic regression analysis were used to count OR and 95% CI. RESULTS:
      762Ala/Ala genotype was overrepresented in the cases (16.9%) compared with
      controls (10.3%), (OR, 1.942; 95% CI, 1.157-3.257, P = 0.011). Multivariate
      analysis showed that two factors were significantly associated with risk of
      gastric cancer, including CagA(+) H. pylori infection (OR, 2.562; 95% CI, 1.174
      5.240, P = 0.037), PARP-1 762AA genotype (OR, 1.772; 95% CI, 1.065-3.867; P =
      0.042). Stratification analysis indicated that among Cag(+) H. pylori positive
      subjects, 762Ala/Ala carriers had higher risk for developing gastric cancer
      compared with 762Val/Val carrier (OR, 2.337; 95% CI, 1.148-4.758; P = 0.017).
      CONCLUSION: PARP-1 762Ala/Ala could be a risk factor for gastric cancer in Han
      Chinese population; PARP-1 762Val/Ala polymorphism and Cag(+) H. pylori infection
      jointly contribute to higher risk for gastric cancer.

PMID- 18716898
TI  - Training tissue bank operators: the International Atomic Energy Agency
      (IAEA)/National University of Singapore (NUS) 10 years of experience.
AB  - National University of Singapore (NUS) was appointed by IAEA to become IAEA/NUS
      Regional Training Centre (RTC) for Asia and the Pacific region in September 1996.
      The Government of Singapore (represented by the Ministry of Environment) with the
      National Science and Technology Board as the funding agency awarded a grant of
      S$225,500 to build a new purpose-built tissue bank to be the Regional Training
      Centre. National University Hospital provided a space of 2,000 square feet for
      this purpose. The first Diploma Course was launched on 3 November 1997 with 17
      candidates with the first NUS Diploma Examination being held in October 1998.
      Between November 1997 and April 2007, a total of nine courses were conducted by
      RTC with a total of 180 tissue bank operators, 133 from Asia and the Pacific
      region (13 countries including 2 from Iran), 14 from Africa (Algeria, Egypt,
      Libya, Egypt, South Africa and Zambia), 6 from Latin America (Brazil, Chile,
      Cuba, Peru and Uruguay), 9 from Europe (Greece, Slovakia, Poland, Ukraine) and 2
      from Australia. The last batch (ninth batch) involved twenty students registered
      in April 2007 and will be due to sit for the terminal examination only in April
      2008.

PMID- 18716897
TI  - An improved design of PCR primers for detection of human T cell receptor beta
      chain repertoire.
AB  - Analysis of T cell receptor beta variable region (TCRBV) gene rearrangement is
      useful for clonal assessment of abnormal T cell proliferations in various
      diseases. However, most primer panels previously used can only amplify the third
      complementarity-determining region. Following IMGT database we established a
      panel of primers, which can amplify entire sequences of all functional TCRBV
      families. To confirm the usefulness of this panel of primers, we detected
      different TCRBV repertoires. In 15 healthy donors, most of the BV families were
      expressed and appeared as a Gaussian distribution. 13 acute myeloid leukemia
      patients showed monoclonal or oligoclonal changes of BV15 family, and some of
      them also had monoclonal or oligoclonal expansion of BV2, BV4, BV6 or BV13
      families. In one patient after allo-hematopoietic stem cell transplantation,
      monoclonal proliferation of BV10 family occurred during graft-versus-host
      disease. In conclusion, this panel of primers improves our abilities to analyze
      TCRBV repertoire changes in related diseases.

PMID- 18716899
TI  - The impact of the International Atomic Energy Agency (IAEA) program on radiation
      and tissue banking in Singapore.
AB  - The National University Hospital (NUH) Tissue Bank was established in October
      1988. The National University of Singapore (NUS) was officially appointed by IAEA
      to be the IAEA/NUS Regional Training Centre (RTC) for RCA Member States for
      training of tissue bank operators on September 18, 1996. In the first five years
      since its establishment the National University Hospital Tissue Bank concentrated
      its work on the sterile procurement and production of deep frozen femoral heads
      and were used in patients for bone reconstruction. The cost of producing these
      tissues were about SGD$ 250 per femoral head although cost fees were initially
      charged at SGD$ 50 per femoral head. The most important activity carried out by
      Singapore within the IAEA was training. Between November 1997 and April 2007, a
      total of nine courses were conducted by RTC with a total of 180 tissue bank
      operators registered, 133 from Asia and the Pacific region (13 countries,
      including 2 from Iran), 14 from Africa (Zambia, Libya, Egypt, Algeria, and South
      Africa), 6 from Latin America (Brazil, Chile, Cuba, Peru, and Uruguay), 9 from
      Europe (Greece, Slovakia, Poland, and Ukraine), and 2 from Australia. The last
      batch (ninth batch) involved 20 students registered in April 2007 and will be due
      to sit for the terminal examination in April 2008.

PMID- 18716901
TI  - Redescription of Ichthyouris bursata Moravec & Prouza, 1995 (Nematoda:
      Pharyngodonidae), a parasite of wild and aquarium-reared discus Symphysodon spp.
      (Osteichthyes).
AB  - The oxyuroid nematode Ichthyouris bursata Moravec & Prouza, 1995
      (Pharyngodonidae) was recorded from the intestine of discus (Symphysodon spp. and
      hybrids) cultured in discus farms in Bangkok and Nonthaburi, central Thailand,
      during 2006 and 2007. This material made it possible to study in detail the
      morphology of this little known parasite species, using both light and scanning
      electron microscopy (the latter not previously used for the male). The SEM
      examination showed taxonomically important morphological features not previously
      reported or erroneously described, including the presence of three bilobed lips,
      a pair of sclerotised plate-like structures and a median cone-shaped outgrowth on
      the posterior cloacal lip, short 'hairs' on the cloacal lips, digital phasmids in
      the male and, sometimes, up to two filaments on the egg poles. This species is of
      South American origin, which was confirmed by its recent record from a free
      living blue discus S. aequifasciatus Pellegrin in Brazil. The reproduction and
      transmission of I. bursata in the conditions of aquarium tanks is probably
      permitted by the direct (homoxenous) life-cycle of this parasite.

PMID- 18716900
TI  - Revision of the order Bothriocephalidea Kuchta, Scholz, Brabec & Bray, 2008
      (Eucestoda) with amended generic diagnoses and keys to families and genera.
AB  - The tapeworm order Bothriocephalidea Kuchta, Scholz, Brabec & Bray, 2008
      (Platyhelminthes: Eucestoda), which has until recently formed part of the
      suppressed order Pseudophyllidea, is revised. Four new genera, namely Andycestus
      n. g. [type- and only species A. abyssmus (Thomas, 1953) n. comb.], Plicocestus
      n. g. [type- and only species P. janickii (Markowski, 1971) n. comb.] (both
      Bothriocephalidae), Mesoechinophallus n. g. [type-species M. hyperogliphe
      (Tkachev, 1979) n. comb.; other species M. major (Takao, 1986) n. comb.
      (Echinophallidae)] and Kimocestus n. g. [type- and only species K. ceratias
      (Tkachev, 1979) n. comb.] (Triaenophoridae) are proposed. Parabothriocephaloides
      Yamaguti, 1934, Penetrocephalus Rao, 1960 and Tetracampos Wedl, 1861 are
      resurrected as valid genera, whereas Alloptychobothrium Yamaguti, 1968 (newly
      synonymised with Plicatobothrium Cable & Michaelis, 1967), Capooria Malhotra,
      1985 and Coelobothrium Dollfus, 1970 (syns of Bothriocephalus Rudolphi 1808),
      Fissurobothrium Roitman, 1965 (syn. of Bathybothrium Luhe, 1902), Paratelemerus
      Gulyaev, Korotaeva & Kurochkin, 1989 (syn. of Parabothriocephaloides Yamaguti,
      1934) and Tetrapapillocephalus Protasova & Mordvinova, 1986 (syn. of Oncodiscus
      Yamaguti, 1934) are considered to be invalid. A recently erected genus,
      Dactylobothrium Srivastav, Khare & Jadhav, 2006, and its type- and only species,
      D. choprai Srivastav, Khare & Jadhav, 2006, are considered to be unrecognisable,
      because their descriptions contain a number of obvious errors and also indicate
      that a mixture of several taxa, probably of at least two cestode orders, were
      studied. Parabothriocephaloides wangi nom. nov. is proposed for
      Parabothriocephalus psenopsis Wang, Liu & Yang, 2004 from Psenopsis anomala in
      China in order to avoid a secondary homonymy. All 46 genera considered to be
      valid are revised, with their generic diagnoses amended on the basis of a
      critical examination of extensive museum and newly collected specimens. Despite
      apparent paraphyly or polyphyly of some bothriocephalidean families, especially
      the Triaenophoridae, the current classification restricted to four families,
      proposed by Bray et al. (1994), namely the Bothriocephalidae, Echinophallidae,
      Philobythiidae and Triaenophoridae, is provisionally retained with slight
      modifications until more molecular data on most genera are available. Keys to
      families and genera are provided.

PMID- 18716902
TI  - Two new species of Pseudorhabdosynochus Yamaguti, 1958 (Monogenea: Diplectanidae)
      from the deep-sea grouper Epinephelus morrhua (Val.) (Perciformes: Serranidae)
      off New Caledonia.
AB  - Three species of monogeneans were collected from Epinephelus morrhua, a deep-sea
      grouper from the external slope of the coral reef, off New Caledonia, South
      Pacific, and are the first parasites recorded from this fish species.
      Pseudorhabdosynochus morrhua n. sp. is characterised by: a sclerotised vagina
      with small sclerotised chambers and a short secondary canal; squamodiscs with
      central rows of rodlets which form closed ovals; and a scaly tegument. P.
      variabilis n. sp. has: a male quadriloculate organ with a characteristic
      structure; a sclerotised vagina in which the primary canal, secondary canal and
      accessory structure are very long and the different parts have various
      arrangements in different specimens; its squamodiscs have central rows of rodlets
      which form closed circles; and a smooth tegument. A prominent vaginal structure,
      comparable to that of P. variabilis, has been found only in P. dolicocolpos
      Neifar & Euzet, 2007, but the species can be distinguished by details of the
      vagina and other structures. A species of Haliotrema Johnson & Tiegs, 1922
      (Ancyrocephalidae) is reported but not described. Specimens of each of the three
      species were present in similar numbers.

PMID- 18716903
TI  - A survey of decision making practices, educational experiences, and economic
      performance of two dairy farm populations in Central Thailand.
AB  - A survey was performed to characterize the dairy production, educational
      experiences, decision making practices, and income and expenses of dairy farms
      and to determine any differences of these practices among two dairy farm
      populations. Farm groups were identified as farms from the Muaklek dairy
      cooperative (Muaklek farms) and farms from other dairy cooperatives (Non-Muaklek
      farms). In April, 2006 questionnaires were distributed to 500 dairy farms located
      in Lopburi, Nakhon Ratchisima, and Saraburi provinces. A total of 85 farms
      completed and returned questionnaires. Means and frequencies were calculated for
      questions across categories and Chi-square tests were performed to determine
      differences among Muaklek and Non-Muaklek farms. Results showed that most farms
      from both groups had a primary or high school educational level, used a
      combination confinement and pasture production system, gave a mineral supplement,
      raised their own replacement females, milked approximately 16 cows/day, used
      crossbred Holstein cows (75% Holstein or more), and mated purebred Holstein sires
      to their cows. More Non-Muaklek farms (P < 0.05; 80%) used a combination of
      genetic and phenotypic information when selecting sires than Muaklek farms (54%).
      Monthly profit per lactating cow, were 1,641 and 1,029 baht for Muaklek and Non
      Muaklek farms, respectively. Overall, information from the study should be useful
      for dairy cooperatives and other dairy organizations when training farmers in the
      future and furthering dairy production research in Thailand.

PMID- 18716904
TI  - Relationship between ketosis and dairy cows' blood metabolites in intensive
      production farms of the periurban area of Dakar.
AB  - This study which involved 140 Holstein and Montbeliard was carried out in the
      periurban area of Dakar with the aim to establish the relationship between
      ketosis, milk production and biochemical blood metabolites. The results showed
      that ketosis is a real problem in periurban farms around the city of Dakar with
      high proportions of 33.57% for subclinical ketosis and 6.43% for clinical
      ketosis. In their second month of milking, cows with subclinical ketosis had a
      decrease of 12.4 and 15.,6% in milk yield respectively for Montbeliard and
      Holstein, whereas cows with clinical ketosis had a decrease of 18.6 and 26%.
      Ketogenic cows (subclinical and clinical) have significantly lower average levels
      of blood glucose (p<0.05) and significantly higher average levels of blood urea
      (p<0.05) than cows with normal blood beta-Hydroxy Butyrate (BbHB) levels. Also,
      from one farm to another, significant difference was recorded with concentration
      of total proteins and globulin, calcium and magnesium.

PMID- 18716905
TI  - Effect of suckling period on calf growth and milk yield of Zebu cows.
AB  - Eighteen multiparous Zebu cows in their third lactation and their calves were
      randomly allocated to three suckling periods, up to 3, 4 or 5 months of age of
      the calf. The cows were individually fed natural hay, cottonseed cake and
      molasses. At 2 months of age, all calves were separated from their mothers, and
      were offered cottonseed cake mixed with molasses and Mucuna hay individually. The
      calves stimulated milk ejection by suckling 30 seconds and suckled the residual
      milk for 45 minutes after milking. The dry matter intake of cows (3.68, 3.29 and
      3.31% of body weight) and calves (2.88, 2.80 and 2.55% of body weight) for
      suckling up 3, 4 and 5 months of age, respectively, was not significantly
      affected by treatment and neither was the growth rate of the calves (178, 157 and
      149 g/d for 3, 4 or 5 months suckling period, respectively). Cows suckling their
      calves up to 5 months had significantly higher milk yield and higher amount of
      saleable milk (1.97, 2.93 and 3.69 kg/cow/d for 3, 4 and 5 months suckling
      period, respectively). The fat content of the milk decreased with increasing
      length of the suckling period while the protein content was not affected. In
      conclusion, a suckling period of 5 months resulted in higher total milk
      production and higher amount of saleable milk but did not seem to have any effect
      on calf growth when the calves were supplemented.

PMID- 18716906
TI  - A cross-sectional study of bovine tuberculosis in the transhumant and agro
      pastoral cattle herds in the border areas of Katakwi and Moroto districts,
      Uganda.
AB  - A study to determine the prevalence of bovine tuberculosis in the transhumant and
      agro-pastoral cattle herds in the border areas of Katakwi and Moroto districts in
      Uganda was carried out from July 2006 to January 2007 using comparative
      intradermal tuberculin test containing bovine and avian PPDs. A total of 1470
      animals, 612 (41.6%) males and 858 (58.4%) females, 883 (60%) young, 555 (37.8%)
      adult and 32 (2.2%) old animals were included. The study involved a cross
      sectional multistage sampling technique with random selection of individual
      animals from a herd. The results revealed a 1.3% overall prevalence of bovine
      tuberculosis in cattle herds in the study area, with a marked variation between
      sub-counties. The highest recorded prevalence was 6.0% in Kapujan, while no cases
      were recorded in Ongogonja, Magoro and Katakwi sub-counties. Distinctly different
      patterns in the avian-bovine reactions were also found in different sub-counties.
      A multivariate logistic regression showed more positive reactions (OR = 6.3;
      95%CI (1.4-26.34) in females than males. BTB prevalence did not differ
      significantly between cattle maintained in pastoral and agro-pastoral production
      systems. The study demonstrated a relatively low prevalence of bovine
      tuberculosis in local zebu cattle reared under traditional husbandry systems in
      Uganda, suggesting low infectiousness of the disease under such mode of
      production. The risk associated with the consumption of raw milk among the
      pastoral communities and that, the pooling of milk together from different
      animals is a common practice, warrants more investigation into the zoonotic
      transmission of tuberculosis within these communities.

PMID- 18716907
TI  - Sheep performance under intensive continuous grazing of native grasslands of
      Paspalum notatum and Axonopus compressus in the subtropical region of the
      Highlands of Central Mexico.
AB  - Liveweight gain was evaluated in tropical Dorper X Pelibuey lambs under intensive
      continuous grazing of native grasslands dominated by Paspalum notatum (PN) or
      Axonopus compressus (AC) in the subtropics of Central Mexico. Two trials were
      undertaken. Trial 1 lasted 12 weeks with 10 lambs (initial weight 18 +/- 2.57 kg,
      3 months old) per treatment in 2002, and Trial 2 for 13 weeks with 8 lambs
      (initial weight 24.0 +/- 2.0 kg, 4 months old) per treatment. Lambs were weighed
      once per week, and liveweight change was estimated by linear regression over day
      of the experiment, using individual regression coefficients as unbiased estimates
      of daily liveweight change; analysed in a random block design. Lambs on Trial 1
      gained 0.061 kg/lamb/day on PN and 0.047 kg/lamb/day on AC (P > 0.05) at an
      overall mean stocking rate of 25 lambs/ha. In Trial 2, liveweight gain was
      significantly larger in PN (0.060 kg/lamb/day) than on AC (0.043 kg/lamb/day) (P
      < 0.05), at a mean stocking rate of 21.5 lambs/ha. It is concluded that intensive
      continuous grazing of native grasslands in the subtropics of the highlands of
      Central Mexico enables moderate liveweight gains for weaned lambs during the
      rainy season; with better results in grasslands dominated by Paspalum notatum.

PMID- 18716908
TI  - Persistent detection of peste de petits ruminants antigen in the faeces of
      recovered goats.
AB  - Peste des petits ruminants (PPR) disease was confirmed in West African Dwarf
      goats. They were managed symptomatically with antibiotics and antidarrhoeics.
      Following clinical recovery, faeces were collected every week from 40 recovered
      goats to monitor excretion of the PPR virus haemagglutinins in their faeces. All
      the 40 recovered goats shed the PPR virus haemagglutinins for 11 weeks post
      recovery. Nine goats (22.5%) continued shedding the viral antigen 12 weeks post
      recovery. There was correlation between weekly mean haemagglutination titre of
      the PPR virus and time post recovery with r = -0.7504 (p < 0.01).

PMID- 18716909
TI  - The detection of antibody against peste des petits ruminants virus in sheep,
      goats, cattle and buffaloes.
AB  - Monoclonal antibody-based competitive ELISA (C-ELISA) has been used for the
      specific measurement of antibodies to peste des petits ruminants (PPR) viruses in
      sheep, goats, cattle and buffalo. Serum samples from sheep (n = 232), goats (n =
      428), cattle (n = 43), buffalo (n = 89) were tested. The animals had not been
      vaccinated against rinderpest or PPR. Findings suggested that the sero-positive
      cases were significantly higher in sheep (51.29%) than in goats (39.02%) (P =
      0.002). The overall sero-prevalence of PPRV in small ruminants was 43.33%. The
      PPR antibodies seroprevalence was 67.42% in buffalo and 41.86% in cattle which
      was significantly higher in buffalo (P = 0.005). The overall sero-prevalence of
      PPRV in large ruminants was 59.09%. Cattle and buffalo sera showed a high
      prevalence of antibody against PPR virus which may explain the difficulty
      experienced in achieving high post-vaccination immunity levels against
      rinderpest. Because antibodies against PPR virus are both cross-neutralizing and
      cross-protective against rinderpest virus, further vaccination in the presence of
      antibodies against PPR virus may be a waste of national resources. It was also
      suggested that antibodies to PPR virus could prevent an immune response to the
      rinderpest vaccine. This paper presents serological evidence for the transmission
      of PPR virus from sheep and goats to cattle and buffalo and highlights the need
      to include PPR serology in the sero-monitoring programme to give a better
      indication of national herd immunity of sheep and goats against PPR.

PMID- 18716910
TI  - Animal production and genetic resources in Guinea Bissau: I--Northern Cacheu
      Province.
AB  - A survey of the animal production systems and genetic resources was conducted in
      Northern Cacheu Province, Guinea Bissau. Animal owners and their families,
      village chiefs, shepherds and local officials were interviewed. The vast majority
      of the population is dedicated to very small-scale subsistence farming where
      animal ownership has an important role in both food supply, ceremonial events and
      as form of cash reserve. Cattle (N'Dama and West African Shorthorn breeds) are
      owned by the two larger ethnic groups in the area, the Felupes and the Balantas
      that have however different management practices. Sheep are relatively scarce
      whereas goats (West African Dwarf) are the most important small ruminant species
      for both ethnic groups. Pigs (crioulo breed) and dwarf chickens play a very
      important role as they are the only species regularly used in trade at the
      village level.

PMID- 18716911
TI  - Animal production and genetic resources in Guinea Bissau: II--Tombali province.
AB  - A survey of the animal production systems and genetic resources was conducted in
      Tombali Province, Guinea Bissau. Animal owners and their families, village
      chiefs, shepherds and local officials were interviewed. The vast majority of the
      population is dedicated to very small-scale subsistence farming where animal
      ownership has an important role in both food supply, ceremonial events and as
      form of cash reserve. Animal production in the area is characterized by the
      existence of several ethnic groups: Balanta, Nalu, Sosso, Biafada and Fula. Only
      Balanta raise cattle (N'Dama and West African Shorthorn) and pig (crioulo breed)
      whereas all ethnic groups own goats (West African Dwarf), chickens and ducks.
      Sheep are limited to specific areas and ethnic groups. The survey is intended to
      serve as a basis to possible agricultural and animal production development
      projects in this area.

PMID- 18716912
TI  - Clinicopathological studies on facial eczema outbreak in sheep in Southwest
      Turkey.
AB  - After very hot summer, 22 sheep from 5 different flocks consisting of
      approximately 150-200 animals each were diagnosed with facial eczema in September
      2005, in southwest Turkey. Photophobia, corneal opacity, severe ulcers of the
      facial skin, especially localized around the eyes and mouth, and 3% mortality
      were the most prominent clinical symptoms. GGT levels of the animals were very
      high and varying between 261- 328 U/l. While the activities of ALT and total
      bilirubin were elevated and AST was normal in affected sheep. Total bilirubin
      level was higher than normal. Seven of the 22 sheep were euthanatized and
      necropsy was performed on all of these animals. Severe icterus, hepatomegaly,
      enlarged gallbladder, congestion of mesenteric vessels were the common necropsy
      findings. Histopathological changes of the liver included necrosis of the
      hepatocytes, cholangiohepatitis characterized by mononuclear inflammatory cell
      infiltrate in the portal area and mild to severe fibrosis around bile ducts. A
      diagnosis of sporidesmin toxicosis was made based on the histopathology of the
      livers, the elevation in liver enzymes, and the development of cutaneous lesions
      consistent with photosensitization and high spore counts in the ruminal contents.
      Surviving sheep were treated with procaine penicillin + dihidrostreptomycin
      sulfate, multivitamin complexes and flunixin meglumine. Additionally, zinc
      sulphate was also given at a dose of 6 gr per 100 lt drinking water for 28 days.
      All treated sheep recovered. Pasture spore counts were between 96,300- 267,500
      spores/g grass.

PMID- 18716913
TI  - Bodyweight and carcass characteristics of Somali goats fed hay supplemented with
      graded levels of peanut cake and wheat bran mixture.
AB  - The experiment was conducted for ninety days of feeding trial at Haramaya
      University, Ethiopia using twenty four yearling male Somali goats weighing 20.4
      +/- 2.02 (mean +/- SD) with the objectives to evaluate the effect of
      supplementation of peanut cake and wheat bran mixture (3:1) on body weight (BW)
      gain and carcass characteristics of Somali goats. The experiment was arranged
      with six blocks and four treatments in a randomized complete block design. The
      treatments were ad libitum feeding of hay (T1, control) and supplementation with
      200 g (T2), 300 g (T3) and 400 g (T4) peanut cake and wheat bran mixture on dry
      matter (DM) basis. Supplementation reduced (P < 0.001) hay DM intake, but
      increased (P < 0.001) total DM intake at 300 g DM (T3) and 400 g DM (T4) level of
      supplementation compared to the control treatment. Daily BW gain, final BW, empty
      BW, hot carcass weight and dressing percent were higher (P < 0.001) in the
      supplemented treatments. Goats on the medium (T3) level of supplementation had
      significantly heavier (P < 0.001) liver and more muscle deposition, whereas those
      on hay alone (T1) exhibited heavier bone, head as well as gut contents (P <
      0.05). It was concluded that supplementation of Somali goats with the different
      levels of peanut cake and wheat bran mixture promoted BW gain, dressing
      percentage and increased the proportion of edible offals. Similarity between the
      different levels of supplementation used in this study with regard to BW and
      carcass characteristics favours the use of the low (T2) or medium (T3) level than
      the high (T4) level of supplementation.

PMID- 18716914
TI  - Reproductive performance analysis of native pig smallholders in the hillside of
      northern Thailand.
AB  - We described the reproductive performance of native pigs raised by smallholders
      in a traditional way and used for ritual sacrifice in a Hmong village in the
      hills of northern Thailand. Field study was conducted between May 2005 and
      January 2007 (13 months in total). The pig reproductive performance in ten
      households during two years (January 2005 to December 2006) was as follows: The
      15 farrowing samples in the households had an average litter size at birth of 7.1
      and litter size at weaning of 6.0 (pre-weaning mortality 16%). A total of 107
      piglets were born in the ten households during the two years, an average of 5.4
      piglets per household per year. We were only able to collect data on farrowing
      intervals in three cases, two of eight months and one of 19 months. There was no
      concentrated farrowing period: of the 15 farrowings, there were seven months with
      one farrowing each (February, April, May, June, July, September, November), four
      with two farrowings (January, March, August, December), and one with none
      (October). This indicates that households have a variety of attitudes to pig
      reproduction, and that there is no seasonality in farrowing.

PMID- 18716915
TI  - Hippocrates revisited? Old ideals and new realities.
AB  - Individual genomics has arrived, personal decisions to make use of it are a new
      reality. What are the implications for the patient-physician relationship? In
      this article we address three factors that call the traditional concept of
      confidentiality into question. First, the illusion of absolute data safety, as
      shown by medical informatics. Second, data sharing as a standard practice in
      genomics research. Comprehensive data sets are widely accessible. Third,
      genotyping has become a service that is directly available to consumers. The
      availability and accessibility of personal health data strongly suggest that the
      roles in the clinical encounter need to be remodeled. The old ideal of physicians
      as keepers of confidential information is outstripped by the reality of
      individuals who decide themselves about the way of using their data.

PMID- 18716916
TI  - The electronic health record as a primary source of clinical phenotype for
      genetic epidemiological studies.

PMID- 18716917
TI  - A novel computational and structural analysis of nsSNPs in CFTR gene.
AB  - Single Nucleotide Polymorphisms (SNPs) are being intensively studied to
      understand the biological basis of complex traits and diseases. The Genetics of
      human phenotype variation could be understood by knowing the functions of SNPs.
      In this study using computational methods, we analyzed the genetic variations
      that can alter the expression and function of the CFTR gene responsible candidate
      for causing cystic fibrosis. We applied an evolutionary perspective to screen the
      SNPs using a sequence homology-based SIFT tool, which suggested that 17 nsSNPs
      (44%) were found to be deleterious. The structure-based approach PolyPhen server
      suggested that 26 nsSNPS (66%) may disrupt protein function and structure. The
      PupaSuite tool predicted the phenotypic effect of SNPs on the structure and
      function of the affected protein. Structure analysis was carried out with the
      major mutation that occurred in the native protein coded by CFTR gene, and which
      is at amino acid position F508C for nsSNP with id (rs1800093). The amino acid
      residues in the native and mutant modeled protein were further analyzed for
      solvent accessibility, secondary structure and stabilizing residues to check the
      stability of the proteins. The SNPs were further subjected to iHAP analysis to
      identify htSNPs, and we report potential candidates for future studies on CFTR
      mutations.

PMID- 18716918
TI  - Association of chromosome 9p21 SNPs with cardiovascular phenotypes in morbid
      obesity using electronic health record data.
AB  - Genomic medicine research requires substantial time and resources to obtain
      phenotype data. The electronic health record offers potential efficiencies in
      addressing these temporal and economic challenges, but few studies have explored
      the feasibility of using such data for genetics research. The main objective of
      this study was to determine the association of two genetic variants located on
      chromosome 9p21 conferring susceptibility to coronary heart disease and type 2
      diabetes with a variety of clinical phenotypes derived from the electronic health
      record in a population of morbidly obese patients. Data on more than 100 clinical
      measures including diagnoses, laboratory values, and medications were extracted
      from the electronic health records of a total of 709 morbidly obese (body mass
      index (BMI) >/= 40 kg/m(2)) patients. Two common single nucleotide polymorphisms
      located at chromosome 9p21 recently linked to coronary heart disease and type 2
      diabetes (McPherson et al. Science 316:1488-1491, 2007; Saxena et al. Science
      316:1331-1336, 2007; Scott et al. Science 316:1341-1345, 2007) were genotyped to
      assess statistical association with clinical phenotypes. Neither the type 2
      diabetes variant nor the coronary heart disease variant was related to any
      expected clinical phenotype, although high-risk type 2 diabetes/coronary heart
      disease compound genotypes were associated with several coronary heart disease
      phenotypes. Electronic health records may be efficient sources of data for
      validation studies of genetic associations.

PMID- 18716919
TI  - Genome mirror 2008.

PMID- 18716920
TI  - Environmental effects on transglutaminase production and cell sporulation in
      submerged cultivation of Bacillus circulans.
AB  - In this research, the effects of pH, temperature, and oxygen on growth kinetics
      of a newly isolated strain of Bacillus circulans from the Amazon and their
      correlations with transglutaminase (TGase) production and cell sporulation were
      investigated. Statistical experimental methods were used to optimize these
      parameters, while induction of sporulation was achieved by oxygen culture
      control. Full factorial composite experimental design and response surface
      methodology were experimentally tested. The model showed that temperature has a
      positive and significant effect on TGase production (P < 0.05) while pH and
      temperature, associated with anoxic conditions, have a marked effect on cell
      sporulation which is consistently linked with TGase production. The contour plot
      of results showed that the best culture conditions for TGase production of B.
      circulans were 30 degrees C, initial pH 8.5, and the highest production was
      obtained in late-stationary culture phase with maximal specific enzyme activity
      of 655 U g(-1) of cells (0.37 U/mL). A correlation between enzyme production and
      cell sporulation, as mediated by oxygen culture conditions, was also demonstrated
      and, although demonstrated only for B. subtilis, it corroborates the molecular
      mechanisms involved in this process. It can be suggested that B. circulans BL32
      is a strong biological system for the industrial production of TGases.

PMID- 18716921
TI  - Analysis of rhamnolipid biosurfactants produced through submerged fermentation
      using orange fruit peelings as sole carbon source.
AB  - The fermentative production of rhamnolipid biosurfactant from Pseudomonas
      aeruginosa MTCC 2297 was carried out by submerged fermentation using various cost
      effective waste materials such as orange peelings, carrot peel waste, lime
      peelings, coconut oil cake, and banana waste. The orange peel was found to be the
      best substrate generating 9.18 g/l of rhamnolipid biosurfactant with a surface
      tension reduction up to 31.3 mN/m. The production was growth independent, and
      optimum conditions were standardized. The emulsifying activity was highest
      against kerosene (73.3%). Rhamnolipid components were purified and separated by
      ethyl acetate extraction, preparative silica gel column chromatography, high
      performance liquid chromatography and thin-layer chromatography. The major
      rhamnolipid components were characterized, by fast atom bombardment mass
      spectrometry, as a mixture of dirhamnolipids and monorhamnolipids.

PMID- 18716922
TI  - Effect of constant glucose feeding on the production of exopolysaccharides by
      Tremella fuciformis spores.
AB  - A fed-batch culture system with constant feeding (glucose 80 g L(-1), 0.25 ml
      min(-1)) was used to study the influence of glucose on cell dry weight and
      exopolysaccharides production from submerged Tremella fuciformis spores in a 5-L
      stirred-tank bioreactor. The results showed that high levels of cell mass (9.80 g
      L(-1)) and exopolysaccharides production (3.12 g L(-1)) in fed-batch fermentation
      were obtained after 1 h of feeding, where the specific growth rate (mu) and
      exopolysaccharides yield on substrate consumed (YP/S) were 0.267 d(-1) and 0.14 g
      g(-1). Unlike batch fermentation, maximal cell mass and exopolysaccharides
      production merely reached 7.11 and 2.08 g L(-1); the specific growth rate (mu)
      and exopolysaccharides yield on substrate consumed (YP/S) were 0.194 d(-1) and
      0.093 g g(-1), respectively. It is concluded that the synthesis of
      exopolysaccharides can be promoted effectively when feeding glucose at a late
      exponential phase.

PMID- 18716923
TI  - Pilot-scale fermentation of aqueous-ammonia-soaked switchgrass.
AB  - Aqueous-ammonia-steeped switchgrass was subject to simultaneous saccharification
      and fermentation (SSF) in two pilot-scale bioreactors (50- and 350-L working
      volume). Switchgrass was pretreated by soaking in ammonium hydroxide (30%) with
      solid to liquid ratio of 5 L ammonium hydroxide per kilogram dry switchgrass for
      5 days in 75-L steeping vessels without agitation at ambient temperatures (15 to
      33 degrees C). SSF of the pretreated biomass was carried out using Saccharomyces
      cerevisiae (D(5)A) at approximately 2% glucan and 77 filter paper units per gram
      cellulose enzyme loading (Spezyme CP). The 50-L fermentation was carried out
      aseptically, whereas the 350-L fermentation was semiaseptic. The percentage of
      maximum theoretical ethanol yields achieved was 73% in the 50-L reactor and 52
      74% in the 350-L reactor due to the difference in asepsis. The 350-L fermentation
      was contaminated by acid-producing bacteria (lactic and acetic acid
      concentrations approaching 10 g/L), and this resulted in lower ethanol
      production. Despite this problem, the pilot-scale SSF of aqueous-ammonia
      pretreated switchgrass has shown promising results similar to laboratory-scale
      experiments. This work demonstrates challenges in pilot-scale fermentations with
      material handling, aseptic conditions, and bacterial contamination for cellulosic
      fermentations to biofuels.

PMID- 18716924
TI  - Ventilation-induced pulmonary vasodilatation in lambs with congenital
      diaphragmatic hernia is modulated by nitric oxide.
AB  - Endogenous nitric oxide (NO) mediates pulmonary vasodilatation at birth, but
      inhaled NO fails to reduce pulmonary vascular resistance (PVR) in newborns with
      congenital diaphragmatic hernia (CDH). This study was designed to investigate the
      effects of ventilation, and the nature of its endogenous mediator, in fetal lambs
      with experimental CDH. Investigations at 138 days of gestation showed that
      ventilation markedly decreased PVR. Inhibition of NO synthesis reduced
      ventilation-induced pulmonary vasodilatation in vivo and increased in vitro
      isometric tension of vascular rings. Ventilation therefore reduces PVR at birth
      in lambs with CDH, and endogenous NO seems to contribute to this reduction.

PMID- 18716925
TI  - Exploration of the genes responsible for unlimited proliferation of immortalized
      lung fibroblasts.
AB  - Regulation mechanism of lung fibroblast proliferation remains unknown. To
      elucidate the key molecules in it, the authors here established mortal and
      immortal nontransformed lung fibroblast cell line/strains with elongated life
      span by telomerase reverse transcriptase gene transfection. Comparing the
      expression profiles of them, 51 genes were explored to be the candidates
      responsible for regulation of cellular proliferation of lung fibroblasts. This
      set of fibrobrast strains of same origin with different proliferative capacities
      may become useful model cells for research on lung fibroblast growth regulation
      and the candidate genes explored in this study may provide biomarkers or
      therapeutic targets of pulmonary fibrosis.

PMID- 18716927
TI  - Repeated measurements of respiratory mechanics in developing rats utilizing a
      forced oscillation technique.
AB  - The ability to successfully intubate the trachea of rats repeatedly over time,
      recover them, and perform repeated measures of changes in respiratory mechanics
      is important. The authors performed experiments utilizing 2 groups of rats at
      various ages in their development. Rats in the single-measurement group were
      studied at 1 age only. Rats in the repeated-measurement group were studied at
      each age point over time. Measurements of respiratory mechanics were made
      utilizing a forced-oscillation technique. We found no differences in respiratory
      mechanics between the 2 groups. Our results demonstrate that developing rats can
      be studied longitudinally to illustrate maturational changes in respiratory
      mechanics.

PMID- 18716926
TI  - CXCR3 ligands contribute to Th1-induced inflammation but not to homing of Th1
      cells into the lung.
AB  - Th1 cells are implicated in numerous pulmonary inflammatory disorders, and
      adoptive transfer of alloreactive Th1 cells mediates lung injury and inflammation
      in mice. In response to Th1-mediated immune injury, CXCR3 ligands IP10 and MIG
      are markedly induced. Because Th1 cells express high levels of CXCR3, their
      recruitment and activity may be influenced by CXCR3 ligands. To examine the role
      of CXCR3 ligands, the authors inhibited CXCR3-ligand interaction by 2 approaches:
      (1) antibody ablation of CXCR3 ligands IP10 (CXCL10/interferon-gamma -inducible
      10-kDa protein) and MIG (CXCL9/monokine-induced by interferon-gamma), and (2) use
      of cxcr3(-/-) mice. Antibody neutralization of IP10 and MIG reduced Th1-cell
      mediated lung inflammation but did not alter Th1-cell influx in the lung. In
      contrast, a lack of CXCR3 on host cells had no effect on Th1 cells influx or
      acute inflammation. In vitro, ablation of endogenous IP10 and MIG inhibited
      antigen-mediated Th1-cell proliferation. These results suggest that the influx of
      alloreactive Th1 cells into the lung does not require CXCR3 ligands, but that
      these chemokines do affect Th1-cell proliferation and activity within the
      affected tissue. Other CXCR3(+) leukocytes do not contribute to acute alloimmune
      injury.

PMID- 18716928
TI  - Alveolar epithelium down-modulates endotoxin-but not tumor necrosis factor alpha
      induced activation of endothelium and selectively inhibits neutrophil
      transendothelial migration.
AB  - In a previous study, the authors reported the development of an optimized model
      bilayer of endothelium with alveolar epithelium using A549 cells, and that
      neutrophil transendothelial migration across endotoxin (lipopolysaccharide [LPS])
      activated endothelial cells was attenuated by the apposition of the epithelium.
      Here the authors investigated whether this modulation by the epithelium extended
      to other stimuli such as tumor necrosis factor (TNF)-alpha, which, like LPS,
      activates proinflammatory gene transcription via nuclear factor (NF)-kappa B
      dependent mechanisms to induce neutrophil transendothelial migration. Unlike the
      response to LPS, neutrophil migration in response to TNF-alpha was not altered by
      the presence of lung epithelial cells, except at a low concentration of TNF-alpha
      upon alveolar directional exposure of the endothelium, i.e., from the epithelial
      side of the bilayer. Epithelial cells in the bilayer reduced expression of E
      selectin on the endothelium in response to LPS, but not with TNF-alpha
      stimulation. The production of the chemokine CXCL8 was also differentially
      modulated by epithelium in response to these 2 mediators. The expression of Toll
      like receptor 4 (TLR4), which is involved in LPS recognition by endothelium, was
      not altered by epithelial cells, suggesting that the anti-inflammatory effect on
      endothelium may be via downstream LPS-induced signaling events. Inhibition of
      some candidate anti-inflammatory mediators produced by epithelium, such as nitric
      oxide, or the activity of interleukin (IL)-10 or transforming growth factor (TGF)
      beta had no effect on the inhibitory influence of the epithelium in the bilayers.
      The authors' findings demonstrate a selective role for alveolar epithelial cells,
      via either direct cell-cell contact or yet-to-be-identified but short-range or
      short-lived product(s) in attenuating endothelial responses to endotoxin.

PMID- 18716929
TI  - Immunological Investigations. Letter from the editor.

PMID- 18716930
TI  - Maternal-fetal immunology.

PMID- 18716931
TI  - Trophoblast immune receptors in maternal-fetal tolerance.
AB  - During pregnancy, interactions between maternal immune cells and fetal
      trophoblast cells of the placenta would seemingly lead to disaster, as the
      trophoblast cells are semi-allogeneic and should trigger rejection by the
      maternal immune response. A fundamental immunologic question of pregnancy as
      posed by Sir Peter Medawar centers on how immunologic disaster is averted. It is
      becoming clear that many different mechanisms act during gestation to render the
      maternal immune system tolerant of the fetus. These include, among others,
      restricted major histocompatibility complex (MHC) protein expression, the
      presence of immunosuppressive B7 family members, immunomodulatory adhesion
      molecules, the expression of apoptosis-inducing proteins, and complement
      regulatory proteins. Understanding of maternal-fetal tolerance has clinically
      important implications for the fields of reproduction, autoimmunity and
      transplantation. Herein are discussed mechanisms by which trophoblast cells are
      protected from maternal immune cell attack. Specifically the role of trophoblast
      cell surface proteins at the maternal-fetal interface is considered.

PMID- 18716932
TI  - Pattern recognition at the maternal-fetal interface.
AB  - Intrauterine infections represent a significant threat to fetal well-being and
      pregnancy outcome. Recent studies suggest that non-immune cells of the maternal
      fetal interface can actively recognize and respond to microbes through pattern
      recognition receptors, in order to control pathogens that may compromise the
      pregnancy. However, these same innate immune responses may inadvertently lead to
      excessive inflammation or apoptosis at the maternal-fetal interface. Thus,
      pattern recognition receptors may play a key role in infection-related pregnancy
      complications. This review discusses what is currently known about the role of
      Toll-like receptors and NOD-like receptors in controlling infections at the
      maternal-fetal interface, and what impact their function may have on pregnancy.

PMID- 18716933
TI  - The role of vascular addressins in implantations sites during successful and
      failing mouse pregnancies.
AB  - Leukocytes are migratory cells. Highly specialized and regulated mechanisms exist
      to control their extravasation from the blood into tissues. Specificity for
      particular organs and tissues is provided by tissue-selective expression of
      vascular adhesion ligands and by tissue-selective chemoattractant factors. The
      successful coexistence of semiallogeneic cells at the maternal/fetal interface
      suggests that the pregnant uterus represents an environment in which leukocyte
      trafficking needs to be exquisitely regulated to establish a selected population
      of maternal leukocytes that support, modulate and regulate trophoblast invasion
      and local immunity. Especially during the critical period of initial placenta
      development in the mouse, there is an elegantly orchestrated progression of
      leukocyte homing events in the decidua basalis associated with the segregation of
      the major infiltrating leukocyte subsets into distinct decidual
      microenvironments. Switches of vascular addressins during the course of pregnancy
      parallel changes in the population of recruited leukocytes and transform the
      leukocyte-rich mid-term decidua basalis into the relatively leukocyte-poor
      phenotype at term. However, these mechanisms are sensitive to disruption.
      Consequently, it is relevant to understand how these mechanisms are modulated
      during abnormal pregnancy, where a dramatically altered decidual leukocyte
      composition may be involved in fetal loss.

PMID- 18716934
TI  - Accumulation of uterine CD16(-) natural killer (NK) cells: friends, foes, or
      Jekyll-and-Hyde relationship for the conceptus?
AB  - Human cycling endometrium and early pregnant decidua are infiltrated by a unique
      lymphocyte subset of CD16(-) natural killer (NK) cells, which are minor cells in
      circulating blood and other organs. The number of uterine (u) CD16(-) NK cells
      rises sharply after ovulation. If pregnancy occurs, uCD16(-) NK cells increase
      further in number, but are shed during the menstrual period. uCD16(-) NK cells
      have the potential to produce cytokines and growth factors that play important
      roles in embryo implantation and placentation, but they are armed with cytolytic
      cytoplasmic granules. In the mid-secretory phase endometrium of women with
      recurrent miscarriages, dense accumulations of uCD16(-) NK cells also occur, like
      those seen in first-trimester decidua of uncomplicated pregnancies. This finding
      complicates understanding the exact roles of these NK cells at implantation
      sites. uCD16(-) NK cells are likely to be a mixture of indigenous endometrial NK
      cells and immigrant NK cells from the circulation. However, it is not yet known
      if NK cells from these two different origins display similar or unique
      characteristics. In this review, the potential underlying mechanisms for
      accumulation of uCD16(-) NK cells in uncomplicated pregnancies and in
      pathological pregnancies, especially recurrent miscarriages, are discussed.

PMID- 18716935
TI  - Chemokine decoy receptors: new players in reproductive immunology.
AB  - Chemokines are multifunctional molecules with roles in leukocyte trafficking and
      developmental processes. Both fetal and maternal components of the placenta
      produce chemokines, which control leukocyte trafficking observed in the placenta.
      Thus, chemokines play roles in the balance between protection of the developing
      embryo/fetus and tolerance of its hemiallogeneic tissues. Recently, a group of
      chemokine receptors, which include D6, DARC, and CCX-CKR, have been described as
      "silent" receptors by virtue of their inability to activate signal transduction
      events leading to cell chemoattraction. Here we review in vitro and in vivo
      evidence indicating that chemokine "silent" receptors regulate innate and
      adaptive immunity behaving as decoy receptors that support internalization and
      degradation of chemotactic factors, and discuss available information on their
      potential role in reproductive immunology.

PMID- 18716936
TI  - Role of dendritic cells in the regulation of maternal immune responses to the
      fetus during mammalian gestation.
AB  - Successful mammalian pregnancy relies on the action of sophisticated regulatory
      mechanisms that allow the fetus (a semi-allograft) to grow and develop in the
      uterus in spite of being recognized by maternal immune cells. Among several
      immunocompetent cells present at the maternal fetal interface, dendritic cells
      (DC) seem to be of particular relevance for pregnancy maintenance given their
      unique ability to induce both antigen-specific immunity and tolerance. Thus,
      these cells would be potentially suitable candidates for the regulation of local
      immune responses within the uterus necessary to meet the difficult task of
      protecting the mother from infection without compromising fetal survival. Current
      evidence on decidual DC phenotype and function, and their role in the regulation
      of the maternal immune system during mouse and human pregnancy are discussed and
      reviewed herein; highlighting novel DC functions that seem to be of great
      importance for a successful pregnancy outcome.

PMID- 18716937
TI  - The role of macrophages in utero-placental interactions during normal and
      pathological pregnancy.
AB  - The intimate association between maternal and placental tissues elicits an
      interesting immunological paradox. Placental tissue contains paternal antigens,
      but under normal circumstances the semi-allogeneic fetus and placenta are not
      attacked by the maternal immune system. Interestingly, this tolerance to fetal
      antigens occurs in the presence of a large number of maternal leukocytes, almost
      all of which are members of the innate immune system. Macrophages are one of the
      most abundant leukocytes in the decidua and their numbers remain constant
      throughout gestation. They are recruited to the decidua by both stromal cells and
      trophoblast cells, where they adopt a specialized phenotype that may assist in
      various aspects of decidual homeostasis, placental development, and tolerance to
      the semi-allogeneic trophoblast. Aberrant behavior of these macrophages can
      affect trophoblast function and placental development, potentially leading to a
      spectrum of adverse pregnancy outcomes ranging from pre-eclampsia to fetal growth
      restriction or demise. This review will focus on the phenotype and putative
      functions of decidual macrophages in normal pregnancy, and how abnormal
      activation of these cells can affect various aspects of placental development.

PMID- 18716939
TI  - Promotion of angiogenesis by human endometrial lymphocytes.
AB  - The human endometrium is a unique tissue that undergoes dramatic monthly
      remodeling during the menstrual cycle in preparation for an implanting conceptus.
      This remodeling involves sequential proliferation and differentiation of
      endometrial stromal and epithelial cells, coupled with extensive angiogenesis and
      infiltration of a specific specialized immune cell subset. Increasing evidence
      points to an essential role for these maternal leukocytes in stimulating the
      endometrial angiogenesis, and we propose that they also play a key role in the
      decidual vascular transformation. Aberrant endometrial angiogenesis,
      decidualisation and vascular transformation is thought to underlie many
      pathologies of pregnancy, from infertility to the development of preeclampsia and
      Intra Uterine Growth Restriction. In this chapter we review the cellular
      processes associated with each stage of endometrial and decidual transformation,
      detailing the role of the immune cell populations and the angiogenic and
      chemotactic factors secreted by them.

PMID- 18716938
TI  - NKT cells at the maternal-fetal interface.
AB  - Establishment of the maternal-fetal interface is characterized by the influx of
      maternal NK cells, macrophages, and T cells into the decidua. Although a great
      deal has been learned about the function of NK cells in the decidua,
      comparatively little is known of decidual T cell function. NKT cells are an
      unusual T cell subset capable of producing both Th1-like and Th2-like cytokines.
      Unlike conventional alphabeta T cells that recognize peptides in the context of
      MHC molecules, NKT cells recognize glycolipids presented by the MHC class I-like
      molecule, CD1d. Recent reports have demonstrated that NKT cells and CD1d are
      present at the maternal-fetal interface. Moreover, activation of NKT cells can
      have dramatic effects on pregnancy. In this article, we will review basic aspects
      of NKT cell biology and summarize the recent literature on NKT cells at the
      maternal-fetal interface.

PMID- 18716940
TI  - Immunological mechanisms affecting angiogenesis and their relation to porcine
      pregnancy success.
AB  - Prenatal mortality due to loss of lymphocyte-promoted endometrial angiogenesis is
      being investigated as a major cause of litter reductions during pregnancy in
      pigs. This review discusses immune mechanisms influencing porcine endometrial
      angiogenesis as well as additional signalling molecules that may play important
      roles in the compromise of peri-implantation and mid-gestation fetal pig
      survival. These include dendritic cells, signalling molecules such as toll-like
      receptors, chemokines and ficolins. Together these cells and molecules regulate
      immune responses and, ideally, protect the mother and prevent immune-based
      conceptus losses. Dendritic cells were recently shown to be angiogenic. Their
      tolerogenic role at the maternal-fetal interface coupled with the ability to
      secrete and respond to angiogenic factors suggests that dendritic cells are the
      key coordinators of angiogenesis at the porcine maternal-fetal interface.
      Chemokines coordinate the localization of immune effector and endothelial cells.
      The balance between pro-angiogenic and anti-angiogenic chemokines is addressed in
      relation to conceptus viability. Ficolins, components of the lectin-mediated
      complement activation pathway, are used for self/non-self recognition. Together,
      these components of the immune system could regulate lymphocyte- and non
      lymphocyte-promoted endometrial angiogenesis to determine conceptus survival.

PMID- 18716942
TI  - Complement inhibition keeps mothers calm and avoids fetal rejection.
AB  - The paternal antigens presented by the fetus could be considered foreign by the
      mother's immune system and elicit an immune response. Here we show that the
      complement system functions as an effector in fetal rejection in two different
      mouse models of pregnancy loss. In a mouse model of fetal loss and growth
      restriction (IUGR) induced by antiphospholipid antibodies (aPL), we found that
      complement activation is a crucial and early mediator of pregnancy loss. We
      demonstrated that C5a-C5aR interaction and neutrophils are key mediators of fetal
      injury. We identified tissue factor (TF) as a critical intermediate that, acting
      downstream of C5 activation, enhances neutrophil activity and trophoblast injury.
      In an antibody-independent mouse model of spontaneous miscarriage and IUGR
      (CBAxDBA) we also identified C5a as an essential mediator. Complement activation
      caused dysregulation of the angiogenic factors (deficiency of free vascular
      endothelial growth factor (VEGF) and elevated levels of soluble VEGF receptor 1)
      required for normal placental development. Inhibition of complement activation
      prevented angiogenesis failure and rescued pregnancies. Our studies in antibody
      dependent and antibody-independent models of pregnancy complications identified
      complement activation as the crucial mediator of damage and will allow
      development of new interventions to prevent pregnancy loss and IUGR.

PMID- 18716941
TI  - Autoimmune disease during pregnancy and the microchimerism legacy of pregnancy.
AB  - Pregnancy has both short-term effects and long-term consequences on the maternal
      immune system. For women who have an autoimmune disease and subsequently become
      pregnant, pregnancy can induce amelioration of the mother's disease, such as in
      rheumatoid arthritis, while exacerbating or having no effect on other autoimmune
      diseases like systemic lupus erythematosus. That pregnancy also leaves a long
      term legacy has recently become apparent by the discovery that bi-directional
      cell trafficking results in persistence of fetal cells in the mother and of
      maternal cells in her offspring for decades after birth. The long-term
      persistence of a small number of cells (or DNA) from a genetically disparate
      individual is referred to as microchimerism. While microchimerism is common in
      healthy individuals and is likely to have health benefits, microchimerism has
      been implicated in some autoimmune diseases such as systemic sclerosis. In this
      paper, we will first discuss short-term effects of pregnancy on women with
      autoimmune disease. Pregnancy-associated changes will be reviewed for selected
      autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus
      and autoimmune thyroid disease. The pregnancy-induced amelioration of rheumatoid
      arthritis presents a window of opportunity for insights into both immunological
      mechanisms of fetal-maternal tolerance and pathogenic mechanisms in autoimmunity.
      A mechanistic hypothesis for the pregnancy-induced amelioration of rheumatoid
      arthritis will be described. We will then discuss the legacy of maternal-fetal
      cell transfer from the perspective of autoimmune diseases. Fetal and maternal
      microchimerism will be reviewed with a focus on systemic sclerosis (scleroderma),
      autoimmune thyroid disease, neonatal lupus and type I diabetes mellitus.

PMID- 18716943
TI  - First international association of hyperthermic oncology Tsudomu Sugahara award.

PMID- 18716944
TI  - 2008 ESHO-BSD Award Winner--Gerard C. van Rhoon.

PMID- 18716945
TI  - Dr. Joan Bull--recipient of the 2008 Robinson Award.

PMID- 18716946
TI  - ThinPrep vitreous-based diagnosis of choroidal malignant melanoma.
AB  - PURPOSE: To report an alternative method for the diagnosis of atypical choroidal
      malignant melanoma-ThinPrep sampling of the vitreous cavity through 25-gauge
      vitrectomy. METHOD: Case report. RESULTS: A 79-year-old gentleman presented with
      a progressive decline in visual acuity in his left eye. A clinical diagnosis of
      large choroidal malignant melanoma was made. Given the history of trauma and the
      possibility of enucleation, the patient wished to have histopathological
      confirmation. The patient underwent 25-gauge vitrectomy. However, he developed a
      choroidal hemorrhage during the procedure and the surgeon elected not to perform
      transretinal biopsy. Instead a sample of the vitreous was evaluated by ThinPrep
      analysis, and a diagnosis of choroidal malignant melanoma was made. CONCLUSIONS:
      Cytological evaluation of vitreous substance with ThinPrep may provide an
      alterative method for a diagnosis in select cases in which FNA is not possible or
      desirable. This technique is straightforward and minimizes the risk of retinal
      detachment or hemorrhage.

PMID- 18716947
TI  - Nocardia asteroides necrotizing scleritis associated with subtenon triamcinolone
      acetonide injection.
AB  - PURPOSE: To report a case of Nocardia asteroides infection after subtenon
      triamcinolone acetonide injection. DESIGN: Case report. RESULTS: An 80-year old
      female received a subtenon triamcinolone acetonide injection for postcataract
      surgery cystoid macular edema. Shortly after, the patient developed a chronic red
      eye that progressed to a fulminant necrotizing scleritis. Eventual scleral biopsy
      revealed Nocardia asteroides infection, which improved after 5 months of systemic
      antibiotic therapy. CONCLUSIONS: Subtenon triamcinolone acetonide injection
      should be recognized as a cause of serious infectious scleritis.

PMID- 18716948
TI  - Nonseasonal allergic conjunctivitis in the tropics: experience in a tertiary care
      institution.
AB  - PURPOSE: To understand the epidemiology, severity, types of pathology, clinical
      features, precipitating factors, and treatment outcomes of patients with allergic
      conjunctivitis in a tropical climate receiving corneal subspecialist
      intervention. A total of 33 patients with severe allergic conjunctivitis under
      corneal subspecialist care in National University Hospital, Singapore were
      studied. DESIGN: A retrospective, noncomparative case series. MAIN OUTCOME
      MEASURES: epidemiological data, clinical features, complete ophthalmological
      examination, and treatment types. METHODS: Both eyes of 33 patients seen at the
      cornea subspecialist clinic between May 2005 and July 2006 were examined at
      baseline, and followed up. Clinical features, treatment given, and outcome
      variables through case sheet review were analyzed. RESULTS: Twenty-five patients
      (75.8%) were male, and 8 (24.2%) were female. Seventeen patients (51.5%) had
      concomitant allergic rhinitis, 16 patients (48.5%) had asthma, and 17 (51.5%) had
      associated dermatitis. Only 9 patients (27.3%) had documented precipitating
      factors. None of the 33 patients said that their symptoms were seasonal; 22
      (66.7%) said their symptoms were perennial. Twenty-nine patients (87.9%) had
      punctate epithelial erosions, and 12 patients eventually progressed to have a
      corneal epithelial defect or shield ulcer (36.4%). Eleven out of the 33 patients
      (33.3%) received topical cyclosporine 0.5%. Of these, only 1 (9.1%) had
      documented complaints of intolerable side effects. CONCLUSION: Allergic
      conjunctivitis in a non-temperate, non-seasonal climate has different clinical
      presentations, and varied precipitating factors. The disease in such conditions
      may respond differently to the usual anti-allergy drug options used in temperate
      countries.

PMID- 18716949
TI  - Endophthalmitis caused by Citrobacter species.
AB  - PURPOSE: To investigate clinical settings, treatments, antibiotic sensitivities,
      and visual outcomes associated with endophthalmitis caused by Citrobacter
      species. METHODS: Data were collected for organisms, surgical intervention,
      antibiotic sensitivity patterns, and final visual acuity. RESULTS: Six eyes of 6
      patients with culture-proven C. freundii (n = 4) or C. koseri(n = 2)
      endophthalmitis were identified. Clinical settings included cataract surgery (1
      eye), cataract surgery combined with trabeculectomy (1), trauma (2), penetrating
      keratoplasty (1), and presumably endogenous source (1). Primary or secondary
      evisceration was performed in 3 eyes. Initial pars plana vitrectomy with
      intravitreal antibiotics was performed in 3 eyes. Final visual acuity was no
      light perception in 5 eyes, and 1 patient with traumatic C. koseri
      endophthalmitis achieved a final vision of 20/30. CONCLUSION: Despite treatment
      with appropriate antibiotics, Citrobacter endophthalmitis can be associated with
      a poor visual outcome. Early detection and management may improve the final
      visual outcome and prevent the possibility of evisceration.

PMID- 18716950
TI  - Optical coherence tomography for classification and clinical evaluation of
      macular edema in patients with uveitis.
AB  - PURPOSE: To study use of optical coherence tomography (OCT) for macular edema in
      uveitis. METHODS: In total, 44 patients with uveitis and macular edema underwent
      OCT. Data obtained were correlated with anatomic type, duration of uveitis, and
      visual acuity (VA). RESULTS: Both cystoid macular edema (CME) and diffuse macular
      edema (DME) correlate negatively with VA, although statistically CME showed
      stronger correlation (p = .02). Also CME had higher mean foveal thickness than
      DME (p < .01). Negative correlation between foveal thickness and VA (p < .05) was
      observed. CME correlates with uveitis duration (p < .01). CONCLUSIONS: CME and
      macular thickening correlate with VA reduction and uveitis duration.

PMID- 18716951
TI  - Azathioprine in the management of autoimmune uveitis.
AB  - PURPOSE: To evaluate the role of azathioprine as an immunosuppressive for steroid
      resistant autoimmune uveitis (AIU). METHODS: Patients using oral prednisolone for
      active AIU without clinical response were recruited. A standard protocol of oral
      prednisolone and azathioprine was used. RESULTS: Twenty-seven patients
      participated in the study: 3 with anterior uveitis, 1 pars planitis, 4 idiopatic
      panuveitis, 8 Vogt-Koyonagi-Harada syndrome, 3 Behcet disease, and 8
      choroidoretinopathies. Complete response was observed in 92%. Eleven patients had
      well-tolerated minor side effects. CONCLUSION: Azathioprine is safe and effective
      in controlling steroid-resistant AIU.

PMID- 18716952
TI  - Infliximab therapy for 2 patients with Vogt-Koyanagi-Harada syndrome.
AB  - PURPOSE: To report the authors' experience using infliximab to treat 2 patients
      with Vogt-Koyanagi-Harada disease (VKH). DESIGN: Interventional case series.
      METHODS: Medical records of the 2 patients were reviewed. RESULTS: After starting
      infliximab intravenous infusions, 5 mg/kg, both patients experienced rapid
      improvement in their VKH disease, and were able to taper and discontinue
      prednisone without disease recurrence for the several-month follow-up period.
      CONCLUSIONS: Infliximab may be effective treatment for VKH, and spares patients
      the side effects of corticosteroids and conventional immunosuppressive drugs.

PMID- 18716953
TI  - Muller cells do not influence leukocyte adhesion to retinal endothelial cells.
AB  - PURPOSE: Diabetic retinopathy is associated with inflammation. The authors
      investigated the influence of Muller cells on leukocyte adhesion to retinal
      endothelial cells. METHODS: ICAM-1 levels were assessed by Western blotting and
      immunocytochemistry. Leukocyte adhesion was quantified using a fluorescence
      assay. RESULTS: High glucose and oxidative/nitrosative stress conditions
      increased ICAM-1 levels in endothelial cells and leukocyte adhesion. Under the
      influence of Muller cells (co-cultures/conditioned medium), the effects were
      comparable to those found when endothelial cells were exposed, alone, to similar
      conditions. CONCLUSIONS: These results show that Muller cells do not influence
      leukocyte adhesion under the in vitro conditions used in this study.

PMID- 18716954
TI  - Pathergy-like reaction following intravitreal triamcinolone acetonide injection
      in a patient with Behcet disease.
AB  - PURPOSE: To describe a patient with Behcet disease who developed a pathergy-like
      reaction following intravitreal triamcinolone acetonide injection. METHODS: Case
      report. RESULTS: A 30-year-old man with a history of Behcet disease received an
      intravitreal injection of triamcinolone acetonide for the treatment of cystoid
      macular edema. The following day, he was noted to have erythematous swelling
      around the injection site. The lesion disappeared spontaneously within 2 weeks.
      CONCLUSION: Pathergy-like reaction to minor trauma may develop not only on the
      skin but also in the mucous membranes such as conjunctiva in patients with Behcet
      disease.

PMID- 18716955
TI  - Ophthalmic manifestations of immune reconstitution inflammatory syndrome
      associated with Cryptococcus neoformans.
AB  - PURPOSE: To describe the ophthalmic manifestations of immune reconstitution
      inflammatory syndrome (IRIS) associated with Cryptococcus neoformans. METHODS:
      Four HIV-positive patients on highly active anti-retroviral therapy (HAART)
      presented with marked optic disk swelling. RESULTS: Three months after the
      episode of IRIS, 2 of the patients maintained 20/20 visual acuity whose elevated
      intracranial pressure (ICP) was successfully managed, while 2 patients visual
      acuities were worse than 20/400 whose ICP was persistently elevated. CONCLUSION:
      Cryptococcus is another opportunistic infectious organism associated with IRIS
      with ophthalmic manifestations. Ophthalmologists have the opportunity to play a
      key role in the early diagnosis and management to prevent serious visual loss.

PMID- 18716956
TI  - Primary bilateral multifocal choroiditis as an initial manifestation of
      disseminated cryptococcosis in a HIV-positive patient.
AB  - PURPOSE: To report a rare case of primary bilateral multifocal choroiditis due to
      disseminated cryptococcus infection in a HIV-positive patient. METHODS:
      Retrospective report. A 30-year-old asymptomatic HIV-positive male referred to us
      for a routine ophthalmic evaluation had bilateral, multiple choroidal lesions.
      CSF confirmed cryptococcus by India ink preparation and antigen by latex
      agglutination. The lesions began to resolve with intravenous amphotericin B and
      oral fluconazole. CONCLUSIONS: Asymptomatic, primary, bilateral multifocal
      choroiditis due to cryptococcus is rare. A routine ophthalmic examination in HIV
      positive patients can alert the treating physician to a possibility of a fatal
      disease.

PMID- 18716957
TI  - Juxtafoveolar telangiectasis associated with CREST syndrome.
AB  - PURPOSE: To report a case of CREST syndrome associated with juxtafoveolar
      telangiectasias (JT). DESIGN: Case report. METHODS: Observational case report.
      RESULTS: A 64-year-old woman affected with CREST syndrome developed bilateral
      visual loss. Capillary dilatation and permeability changes in the outer retina
      were noticed during an angiographic study. Optical coherence tomography (OCT)
      showed thickening with loss of the foveal depression and inner lamellar cyst. The
      patient was diagnosed as stage 3, group 2A JT associated with CREST syndrome.
      CONCLUSIONS: Finding JT in association with CREST syndrome suggests a common
      pathophysiologic process.

PMID- 18716958
TI  - Ocular manifestation of primary VZV infection in a splenectomized patient.
AB  - PURPOSE: To report a rare case of primary varicella zoster virus (VZV)-associated
      retinal vasculitis in a splenectomized patient. DESIGN: Case report. RESULTS:
      After manifestation of VZV-associated retinal vasculitis, a splenectomized
      patient experienced binocular loss of vision. CONCLUSIONS: For the development of
      VZV-associated uveitis, the presence of specific T cells are necessary. Here, the
      authors present a rare case of VZV-associated retinal vasculitis in a
      splenectomized patient.

PMID- 18716960
TI  - Assessment of the accuracy of lacrimal scintigraphy based on a prospective
      analysis of patients' symptomatology.
AB  - BACKGROUND: Dacryoscintigraphy is a noninvasive method frequently used for
      assessment of the lacrimal drainage system. Sometimes conflicting results with
      patients' complaints are obtained, which have no clear explanation. In our
      hypothesis, follow-up of patients evaluated with dacryoscintigraphy could be
      helpful in determining possible explanations for these conflicting results.
      METHOD: Thirty-eight consecutive patients (76 eyes) who had not previously
      undergone dacryocystorhinostomy or probing were entered in the study. Following
      instillation of 4 MBq (99m)Tc-pertechnetate, a routine procedure of
      dacryoscintigraphy was performed. After a mean follow-up time of 1.2 +/- 0.3
      years (range 0.9-1.6 years), all patients were reassessed clinically. RESULTS:
      Using initial patients' symptoms as the gold standard, the sensitivity,
      specificity, NPV, and PPV of dacryoscintigraphy were calculated to be 82.1%, 75%,
      60%, and 90.1%, respectively. The kappa value as a measure of agreement was 0.52.
      Considering the follow-up study as the gold standard, the sensitivity,
      specificity, NPV, and PPV were calculated as follows, respectively: 96.3%, 90.4%,
      96.3%, and 90.4%. The kappa value was 0.86. There were three initially symptom
      free eyes with obstructive pattern on the scans, which developed epiphora on the
      follow-up. In fact, these eyes were initially classified as false positive, but
      follow-up assessment showed that they were true-positive scans in a subclinical
      state. CONCLUSION: Despite certain drawbacks inherent to the technique,
      dacryoscintigraphy provides valuable independent information and allows more
      accurate management decisions. In some patients, data obtained from lacrimal
      scintigraphy could be predictive, and it makes possible determination of
      subclinical nasolacrimal duct obstructions.

PMID- 18716961
TI  - Bacteriology of chronic dacryocystitis in adult population of northeast India.
AB  - PURPOSE: To determine the pattern of bacteriology of chronic dacryocystitis in
      the Northeast Indian population and compare it with previous studies. METHODS: A
      prospective analysis of 543 lacrimal sac content of 421 patients in the period of
      October 2003 to June 2007. Material obtained directly from the lacrimal sac
      during making sac flap that had undergone external dacryocystorhinostomy for
      chronic dacryocystitis. RESULTS: Five hundred eighty-four bacteria were isolated
      from 543 specimens of 421 patients. Growths were observed in 494 (90.97%)
      specimens, and there was no growth in 49 (9.03%) of the specimens; 61.04% were
      female and 38.95% were male. Four hundred ninety-four samples (90.97%) were
      positive for bacteria, including both single and mixed isolations. Four hundred
      five (74.58%) had single isolations, 89 (16.39%) patients had mixed bacterial
      isolations (more than one organism), and no organisms were isolated from 49
      (9.02%) specimens. The majority of microorganisms in our study were gram-positive
      bacteria, 75% of the overall microorganisms cultured were gram-positive bacteria,
      with a predominance of staphylococcus species. Gram-negative bacteria were
      isolated in 25% of the specimens with predominance of Pseudomonas aeruginosa.
      CONCLUSIONS: It is important to have knowledge of the microbial organisms
      responsible for chronic dacryocystitis in a particular geographical area to
      choose the prophylactic antibiotic following lacrimal drainage procedure.
      Identification of the microbes and proper antibiotic prophylaxis helps for the
      better management of the postoperative period.

PMID- 18716962
TI  - Combined surgical method of orbital and periorbital hemangioma treatment in
      infants.
AB  - PURPOSE: To analyze the results of application of combined surgical treatment in
      different forms of hemangioma in infants. MATERIALS AND METHODS: One hundred
      seventy-four children with different forms of orbital and periorbital hemangiomas
      aged 1-16 months (mean age 5.2 + 1.97 months) were operated on at the pediatric
      ophthalmology department. Fast growth of hemangioma, both superficial
      (intradermal) and deep (subdermal and orbital) localization, significant
      deformity of eyelids, with narrowing of eye fissure were the indications for
      surgical treatment. The combined-staged method, including cryosurgery of
      superficial intradermal lesions and surgical excision of subdermal and/or orbital
      parts of the tumor in different combinations depending on the form and depth of
      hemangioma spreading, was applied. RESULTS: Usage of cryodestruction usually on
      the first stage of treatment allowed gentle scarring of the angiomatously changed
      skin areas. Surgical excision of the deep part of the tumor eliminated
      disfigurement and visual axis occlusion, avoiding amblyopia development. Good
      cosmetic and anatomic result was achieved in 90.4% of cases. CONCLUSION: Combined
      surgical method of treatment of progressive capillary hemangiomas by using
      cryosurgery and surgical excision in infants allows the choice of optimum tactics
      depending on features of the course and clinical picture in each individual case
      and provides achievement of high cosmetic and functional result of treatment. The
      early beginning of treatment in cases of fast progressing of the tumor allows
      prevention of extensive skin affection and amblyopia development.

PMID- 18716963
TI  - Digital photography as a novel technique of measuring ocular surface dimensions.
AB  - PURPOSE: To introduce a novel technique for measuring ocular surface dimensions
      using digital photography and computerized image analysis in the context of
      ptosis repair surgery. METHODS: Digital photographs and patient questionnaires on
      dry eye symptoms were obtained from 31 patients before and after ptosis repair.
      Patients were examined preoperatively and at 1 and 6 weeks postoperatively. Adobe
      Photoshop 7.0 (Adobe Systems Incorporated, 345 Parkl Avenue, San Jose, CA 95110
      2704, USA) was used to digitally measure palpebral fissure height, fissure width,
      and ocular surface area (OSA). Similar digital measurements were obtained on 30
      control subjects as well. Digital calculations of OSA for control, preoperative,
      and postoperative groups were compared with other published techniques. RESULTS:
      Graphical comparison between our method of measuring OSA and the mathematical
      estimations proposed by previous studies suggests that our method is more precise
      in measuring OSA, and that it is also better able to identify individual
      variations of OSA from general population trends. CONCLUSION: Digital ocular
      photography combined with computerized image analysis is a fast, easy to use, and
      reliable method of measuring ocular surface dimensions. In addition to ptosis
      surgery, this method can be used in other ocular surface studies.

PMID- 18716964
TI  - Orbital tuberculosis: a review of the literature.
AB  - PURPOSE: To provide an up-to-date review of the clinical presentations,
      investigations, and management of orbital tuberculosis (OTB). METHODS: Systematic
      review of the literature concerning OTB, limiting the results to English-language
      peer-reviewed journals. RESULTS: Seventy-nine patients from 39 publications were
      identified as cases of OTB. The condition presents in one of five forms:
      classical periostitis; orbital soft tissue tuberculoma or cold abscess, with no
      bony involvement; OTB with bony involvement; spread from the paranasal sinuses;
      and tuberculous dacryoadenitis. The ocular adnexa, including the nasolacrimal
      system and overlying skin, may also be involved. CONCLUSIONS: Diagnosis can be
      difficult and may necessitate an orbital biopsy, in which acid-fast bacilli (AFB)
      and characteristic histopathology may be seen. Growth of Mycobacterium
      tuberculosis (mTB) from such a specimen remains the gold standard for diagnosis.
      Ancillary investigations include tuberculin skin tests and chest radiography, but
      more recently alternatives such as whole blood interferon-gamma immunological
      tests and PCR-based tests of pathological specimens have proven useful. The
      management of OTB is complex, requiring a stringent public health strategy and
      high levels of patient adherence, combined with long courses of multiple anti
      tuberculous medications. The interaction of the human immunodeficiency virus
      (HIV) with TB may further complicate management.

PMID- 18716965
TI  - The practice of dacryocystorhinostomy (DCR) surgery by ophthalmologists in the
      United Kingdom (UK).
AB  - PURPOSE: To study the practice of dacryocystorhinostomy (DCR) surgery by
      ophthalmologists in the United Kingdom (UK) looking at the evaluation techniques
      used, surgical variations, and follow-up management of DCR cases. METHODS: A mail
      shot questionnaire was designed and distributed to every UK consultant
      ophthalmologist on the specialist register held by the Royal College of
      Ophthalmologists. The questionnaire consisted of eight questions and an image of
      a typical DCR candidate so respondents could illustrate details of their surgical
      incision. The data received was entered into a database and analyzed with the
      SPSS statistical package. The variation in incisions was divided into various sub
      types and quantified accordingly. The chi-square test and analysis of variance
      (ANOVA) were used to calculate significance, which was set at p < 0.05. RESULTS:
      A response rate of over 75% was achieved amongst the 800 questionnaires
      dispatched, almost one-third of which perform DCR surgery. Of these, almost 50%
      were non-lacrimal specialists. The majority never use the endonasal approach,
      with 59% never performing preoperative nasal endoscopy. Most respondents use a
      standard incision 10-15 mm long with routine silicone intubation. Lacrimal
      specialists tended to remove tubes earlier (week 4 to 8) and suture posterior
      flaps more often than non-specialists. Significant differences in practice were
      found between lacrimal and non-lacrimal specialists in most parameters, in
      addition to differences between members and non-members of the National
      Oculoplastic Surgery Society. CONCLUSIONS: A minimum of 200 DCR surgeons are
      practicing in the UK where almost 50% are non-lacrimal specialists. Marked
      variations exist in the perioperative DCR practice.

PMID- 18716966
TI  - The transglabellar/subcranial approach for surgical excision of periocular second
      tumors in retinoblastoma.
AB  - PURPOSE: To evaluate the use of transglabellar/subcranial approach for surgical
      resection of periocular second non-ocular tumors in retinoblastoma patients.
      METHODS: Seven retinoblastoma patients with periocular second tumor involving
      anterior skull base underwent surgical resection by transglabellar/subcranial
      approach in a single center. The medical records of these patients were
      retrospectively evaluated. RESULTS: The most common presenting symptom in
      retinoblastoma patients with periocular second tumor was difficulty in
      maintaining the prosthesis in three patients (43%), followed by epistaxis in one
      (14%), palpable orbital mass in one (14%), persistent periocular swelling in one
      (14%), and visual loss in one (14%) patient. Periocular second tumors were
      leiomyosarcoma in three (43%) patients, osteosarcoma in three (43%), and sphenoid
      wing meningioma in one (14%) patient. Surgical resection by the
      transglabellar/subcranial approach was the only treatment in one (14%) patient
      with sphenoid wing meningioma and was combined with chemotherapy in three (43%)
      patients, and with both external beam radiotherapy and chemotherapy in three
      (43%) patients. Surgical margins were negative in three (43%) patients and
      microscopically positive in four (57%) patients. Complications were minor,
      including cerebral spinal fluid (CSF) leak in one (14%) patient and CSF leak and
      subgaleal hematoma in one (14%) patient. After 31 months mean follow-up, three
      (43%) patients were alive and four patients (57%) were dead. CONCLUSIONS:
      Retinoblastoma patients with periocular second tumors have a poor prognosis. The
      transglabellar/subcranial approach can be used for surgical resection of
      periocular second tumor involving skull base with low morbidity.

PMID- 18716967
TI  - Bilateral infiltrative disease of the extraocular muscles: a rare clinical
      presentation of early stage chronic lymphocytic leukemia.
AB  - Orbital involvement in chronic lymphocytic leukemia (CLL) is highly unusual and
      most commonly involves hemorrhage or soft tissue infiltration in advanced
      disease. We report a case of rapid onset bilateral orbital muscle infiltration as
      the presenting feature of early stage CLL. In addition, we demonstrate clinico
      pathological correlation with an identical chronic B-cell lymphocytic infiltrate
      in both orbit and bone marrow, with good response of the orbital disease to local
      radiotherapy.

PMID- 18716968
TI  - A complex orbit.
AB  - Wegener's Granulomatosis (WG) in its limited form can be a challenging diagnosis.
      ANCA, radiological investigations and histology should be interpreted in light of
      clinical findings. A delay in diagnosis can have profound visual consequences.
      Immunosuppressive therapy and co-morbidities can mask signs of orbital sepsis. A
      low threshold for further exploration and biopsy should be maintained if an
      orbital abscess is suspected. This report describes a complex case of WG that
      illustrates the diagnostic and therapeutic challenges inherent in this form of
      orbital inflammatory disease.

PMID- 18716969
TI  - Diagnosis and treatment of a superficial upper eyelid arteriovenous malformation.
AB  - Combined embolization and surgical excision as a safe treatment for a high flow
      superficial upper eyelid anteriovenous malformation. INTRODUCTION: Orbital
      arteriovenous malformations (AVM) may cause significant morbidity including
      chronic pain and cosmetic disfigurement. These rare lesions require a
      multidisciplinary approach. A case of an orbital high-flow AVM treated
      subsequently by an mterventional radiologist and oculoplastic surgeon is
      presented. MATERIALS AND METHODS: Clinical assessment, computed tomography and
      digital substruction angiography revealed a high-flow AVM. Transvenous and
      percutaneous embolization was followed by surgical excision. RESULTS: A 1.5 cm,
      slowly growing, compressible pulsating lesion in the left upper eyelid of a 23
      year old man was found. Eye motility and ophthalmologic examination were normal.
      Valsava manoeuvre didn't increase the size. Imaging revealed a high-flow AVM
      feeded by the arteria temporalis superficialis (itself feeded by the a.
      supraorbitalis and supratrochlearis). Draining vessels were the superior
      ophthalmic vein and a superficial lateral orbital vein. This malformation was
      first embolized. To prevent iatrogenic embolization of the sinus cavernous, the
      vein draining into the superior ophthalmic was occluded by a transvenous
      approach, followed by a percutaneous injection with diluted glue (equal amounts
      of glubran-2 and lipiodol). The remaining low-flow lesion was then safely
      excised. CONCLUSION: High-flow orbital AVM represent a considerable treatment
      challenge. Good cosmetical and functional outcome was obtained safely by
      subsequent embolization and surgical excision. When treating these rare
      malformations it is of the highest importance to coordinate the interdisciplinary
      efforts.

PMID- 18716970
TI  - Iatrogenic lateral rectus transection secondary to dental implantation surgery.
AB  - A 48-year-old patient noted right subconjunctival hemorrhage and double vision
      immediately following dental implant surgery. CT scan confirmed implant screw
      misplaced into the right orbit, and exploration revealed transection of right
      lateral rectus muscle belly. Diagnostic and management challenges are discussed.

PMID- 18716971
TI  - Mature orbital teratoma presenting as a recurrent orbital cellulitis with an
      ectopic tooth and sphenoid malformation-a case report.
AB  - An unusual case of an orbital teratoma presenting as recurrent orbital cellulitis
      in a 2-year-old child. Imaging studies demonstrated an extraconal mass with a
      bony defect and a malformation of the sphenoid. An ectopic tooth was also
      present. Malformation and defects in the sphenoid have not been previously
      reported in association with intraorbital teratoma. Attention is drawn to the
      need for imaging in children presenting with orbital infections in order to
      exclude an intraorbital mass.

PMID- 18716972
TI  - Oculocerebrocutaneous syndrome: a case report.
AB  - There are many congenital ocular malformations associated with systemic findings.
      In cases such as oculocerebrocutaneous syndrome, the severity of systemic
      findings makes diagnosis particularly important. This case report presents a case
      of this uncommon syndrome and demonstrates the common findings.

PMID- 18716973
TI  - Orbital lymphoma presenting as an unstable ocular prosthesis: a salutary lesson.
AB  - We report the unusual presentation of an extranodal marginal zone B-cell lymphoma
      presenting as instability of an ocular prosthesis. More commonly, the stability
      of an ocular prosthesis can be affected by orbital implant migration, sunken
      superior sulcus, eyelid malformations, shallow inferior fornix, and contracted
      sockets (Charlton & Weinstein, 1995). Although rare, this case highlights the
      importance of meticulous examination of the socket, including careful palpation
      for any potential masses. To our knowledge, instability of an ocular prosthesis
      in association with orbital lymphoma has not been described previously.

PMID- 18716974
TI  - Orbital meningioma after cranial radiation for acute lymphocytic leukemia.
AB  - PURPOSE: To describe the ophthalmic findings of cranial radiation-induced orbital
      meningioma after acute lymphocytic leukemia therapy. METHODS: This is a
      prospective clinical report. RESULTS: We describe two patients recently evaluated
      with orbital meningiomas many years after cranial radiation for acute lymphocytic
      leukemia. CONCLUSIONS: There will probably be more of these cases in the next
      several years. Unlike primary meningiomas, these neoplasms have a tendency to be
      more diffuse, multiple, and may undergo malignant degeneration.

PMID- 18716975
TI  - Severe, permanent orbital disease in herpes zoster ophthalmicus.
AB  - A 63-year-old man with HZO presented with involvement of cranial nerves II, III,
      IV, V, and VI, with proptosis, raised intraocular pressure, and chemosis. With
      the aid of orbital imaging, a diagnosis of orbital apex inflammation secondary to
      HZO was confirmed, and he was treated with intravenous acyclovir and oral
      steroids. Despite this, he made a minimal recovery at eight months following
      presentation. Severe, irreversible orbital disease may develop following HZO, and
      an ischemic vasculitis may play a role in the pathogenesis of the disease.

PMID- 18716976
TI  - Trichomegaly induced by erlotinib.
AB  - Erlotinib (Tarceva, Roche) is a chemotherapeutic agent used in the management of
      advanced non-small cell lung cancer and other malignancies. We present the case
      of a patient who developed excessive eyelash growth, called trichomegaly, a rare
      ocular side effect of this drug.

PMID- 18716977
TI  - An unusual presentation of merkel cell carcinoma of the eyelid.
AB  - Merkel cell carcinoma is a rare primary neuroendocrine tumor occurring on any
      part of the body. It usually presents as a firm, nontender, violaceous, or purple
      nodule located on areas of the body that have been exposed to sunlight. A 68-year
      old female presented with a rapidly growing lesion on the left lower eyelid from
      6 weeks. Examination showed a 4 cm diameter, exophytic, ovoid skin lesion of the
      left lower lid. Wide local excision of this lesion was followed by adjuvant
      chemotherapy. Histological examination of therapeutic frozen section of the
      lesion and the presence of neuroendocrine marker and cytokeratin markers
      established the diagnosis of Merkel Cell carcinoma. The follow-up at 8 months was
      uneventful. Merkel cell carcinoma can have an unusual presentation of a large,
      exophytic, oval lesion resembling a basal cell carcinoma. Merkel cell carcinoma
      has predilection for rapid spread; hence, in a case of lid lesions, a suspicion
      for this diagnosis should be kept in mind.

PMID- 18716979
TI  - [Acute respiratory infections: new viruses, less therapy options?].

PMID- 18716980
TI  - Why early surgery may not be enough: the search for new therapeutic strategies in
      cryptorchidism.

PMID- 18716981
TI  - Extreme hyponatremia in an infant with congenital adrenal hypoplasia due to a
      novel NR0B1 (DAX-1) mutation.
AB  - BACKGROUND: Extreme hyponatremia (<105 mmol/l) has rarely been reported in
      infants. It is potentially life-threatening and requires intensive care
      treatment. PATIENT: We report on a male infant with absence of weight gain from
      birth to day 33 of life despite adequate nutrition. On admission serum sodium and
      potassium were 104 and 5.9 mmol/L respectively. The infant's physical status
      revealed dehydration, but normal activity with no apparent neurological,
      circulatory or respiratory impairment. MAIN RESULTS: Global adrenocortical
      insufficiency was diagnosed and treated with hormonal substitution in addition to
      intravenous application of fluid, glucose and electrolytes. The rise of serum
      sodium was carefully monitored and adjusted to a target rate of 0.5 mmol/L/h. X
      linked adrenal hypoplasia congenita (X-AHC) was confirmed by the identification
      of a novel nonsense NR0B1 (DAX-1) mutation (W236X). CONCLUSIONS: X-AHC in infants
      may present as failure to thrive despite adequate nutrition. Extreme hyponatremia
      may be associated with little symptoms if developing slowly. Rehydration and slow
      correction of serum sodium with solutions containing less sodium than normal
      saline is essential.

PMID- 18716982
TI  - [Human Bocavirus-infection (HBoV): an important cause of severe viral obstructive
      bronchitis in children].
AB  - BACKGROUND: Apart from established pathogens of lower respiratory tract
      infections, such as respiratory syncytial virus (RSV), an increasing number of
      additional agents has been identified in recent years. In 2005 the human
      bocavirus (hBoV) has been isolated from respiratory tract samples and has been
      reported worldwide with frequencies ranging from 1.5 to 18.3% in respiratory
      samples from children with airway infections. PATIENTS: We investigated 173
      specimens of a total number of 162 children who were inpatients with severe
      respiratory tract infections most of whom required oxygen therapy. METHOD: We
      analyzed respiratory tract samples (83% nasopharyngeal washes, 15% tracheal
      secretions, 2% bronchoalveolar lavages) for adenoviruses, influenza A und B
      viruses, parainfluenzaviruses types 1 to 3 and RSV using antigen-specific
      immunofluorescence assays. Additionally we tested human metapneumovirus (hMPV)
      and hBoV using a PCR assay. MAIN RESULTS: 35.8% specimens were negative in all
      assays, 54.3% were positive for RSV and 9.8% were positive for adeno-, influenza
      , parainfluenzaviruses or hMPV. HBoV could be detected in 17 specimens (9.8%),
      defining HBoV to be the second most frequent pathogen. Nine of these patients
      showed a coinfection with RSV, one with parainfluenza virus. Viral loads did
      range from 2x10 (2) to 5.6x10 (10) genome equivalents/ml with higher viral loads
      being observed in the first days after disease onset. Most children were infected
      in the months between December and April. Half of the patients with isolated HBoV
      infection showed rhinopharyngitis, a third suffered from pulmonary obstruction
      and nearly every second required oxygen therapy. However, no HBoV-specific
      symptoms were found. CONCLUSION: HBoV is a common pathogen causing viral
      respiratory tract infection in infants and young children. Among the here
      reported patients HBoV was the second most frequent identified pathogen. X-ray
      studies frequently revealed peribronchial and pneumonic infiltrates with only
      moderately elevated laboratory inflammatory markers. So far, no HBoV-specific
      clinical symptoms are known. Additional questions for example related to the way
      of transmission and optimal treatment remain to be investigated in prospective
      studies.

PMID- 18716983
TI  - Double balloon endoscopy for detection of small-bowel adenomas in familial
      adenomatous polyposis after pancreaticoduodenectomy according to Whipple.
AB  - Patients with familial adenomatous polyposis (FAP) have a 5%-10% lifetime risk of
      developing duodenal cancer. In severe duodenal polyposis, pancreaticoduodenectomy
      according to Whipple has been considered the only way to cure duodenal polyposis.
      However, polyps recur even after surgery. We describe a patient with severe
      adenomatosis of the small bowel in the afferent loop of a Roux-en-Y anastomosis
      after a Whipple procedure, detected by double balloon endoscopy (DBE). This is
      the first description of the use of DBE for this indication, and emphasizes the
      need for surveillance of the small bowel after surgery, especially in the area of
      the biliary anastomosis.

PMID- 18716984
TI  - [Experience with the s-GAP flap for autologous breast reconstruction].
AB  - In breast reconstruction with autologous tissue the DIEP flap has become the gold
      standard in recent years. The superior gluteal artery perforator (s-GAP) flap is
      an alternative harvested from the buttock. We present our experience with the s
      GAP flap and discuss its role in breast reconstruction. All s-GAP flaps performed
      for breast reconstruction in the Department of Plastic and Hand Surgery,
      Behandlungszentrum Vogtareuth from June 2002 until February 2007 were
      retrospectively analysed. Out of 59 flaps 4 flaps failed, the success rate was 94
      %. Partial or fat necrosis occurred in 2 cases. The s-GAP flap served as a safe
      reconstructive alternative to the DIEP flap. Advantages of the s-GAP flap are
      reliable perforators, the safe vascular supply and the firm fat structure which
      facilitates the breast reconstruction. The donor site morbidity is minimal, the
      gluteal muscles stay intact and the scar is easy to hide in the underwear.
      Disadvantages are a demanding preparation with a prolonged operating time
      compared to the DIEP flap. The s-GAP flap is a reliable and safe option for
      autologeous breast reconstruction. It is the method of choice for staged
      bilateral breast reconstruction or if the DIEP flap is not available,
      particularly in the thin patient.

PMID- 18716985
TI  - [Alternative autologous breast reconstruction using the free microvascular
      gracilis muscle flap with horizontal skin island].
AB  - BACKGROUND: While free TRAM or DIEP flaps are still the most common techniques
      for autologous breast reconstruction, there are also other flaps which are
      suitable for patients who are not candidates for a TRAM/DIEP flap. In addition to
      the S-GAP or I-GAP, the transverse myocutaneous gracilis (TMG) flap is an
      excellent alternative. The tissue utilised is taken from the medial thigh and
      inferior gluteal area. PATIENTS AND OPERATIONS: We have performed 37 TMG flap
      operations on 23 patients since 2007. The indications were breast cancer,
      asymmetry of the breasts and capsular fibrosis. The average age of our patients
      was 47 years. Incisions are similar to those of a transverse thigh lift. The flap
      is nourished by perforators from the gracilis and its proximal dominant pedicle.
      The landmark ventrally is the greater saphenous vein and midpoint of the inferior
      gluteal fold on the dorsal side. Its size can go up to 30 x 10 cm. Recipient
      vessels are the internal thoracic vessels. The donor site is closed primarily.
      All of our patients are immobilised for 2 days and were instructed to avoid
      sitting for 2 weeks. RESULTS: 12 patients were reconstructed after breast cancer,
      8 patients had a capsular fibrosis and 3 patients had an asymmetry. The follow-up
      period was 8 months. Mean operating time for unilateral reconstruction is 220
      minutes, for bilateral reconstruction 325 minutes. The weight of the flaps varied
      from 220 to 440 grams. It takes approximately 30 minutes to harvest the flap.
      There was no flap loss. Some of the patients described a tight feeling on the
      thighs for 3 weeks. They described a hypaesthesia on the dorsal thighs. There was
      one delayed wound healing caused by haematoma. CONCLUSION: In our department, the
      TMG has become the most preferred flap for breast reconstruction besides the
      TRAM/DIEP. Especially slim patients with small breasts or a history of surgery on
      the abdominal wall are ideal candidates. The tissue from the medial thigh is very
      similar to the breast tissue. The constant vascular anatomy makes it easy to
      harvest the flap. The resulting scar is well hidden in the patients' underwear.

PMID- 18716986
TI  - [Prophylactic mastectomy in women at high risk for breast cancer: indications and
      options].
AB  - In women at high-risk for breast cancer, bilateral prophylactic mastectomy
      achieves a risk reduction of up to 95 percent. Provided that proper indications
      are adhered to and informed consent has been obtained, prophylactic mastectomy
      can be performed starting at the age of 25 years. As an option, in BRCA1/2
      mutation carriers with hereditary breast and ovarian cancer, bilateral
      prophylactic ovarectomy and salpingectomy reduce the risk of breast cancer by 50
      percent and the risk of ovarian cancer by 90 percent. In women of at least 35
      years of age and without wish for child bearing, this means of surgical
      prevention is often suggested at present. The database on chemoprevention in
      premenopausal high-risk women remains to be defined and procedures are currently
      advised in conjunction with clinical trials only. As opposed to more radical
      ablative techniques, we favour subcutaneous mastectomy as a prophylactic means in
      women at high risk for breast cancer. It combines oncological safety and
      excellent aesthetic results if performed with the correct surgical technique.
      Both aspects are of fundamental importance to the often young and still healthy
      women with this indication who are confronted with the difficult decision for or
      against a prophylactic mastectomy.

PMID- 18716987
TI  - [The oculocardiac reflex in blepharoplasties].
AB  - The oculocardiac reflex (OCR) is a well-known phenomenon in ophthalmic surgery,
      but is rarely described in aesthetic blepharoplasty surgery. It was first
      mentioned in 1908 by Ascher and Dagnini. Since then, ophthalmologists and
      anaesthesiologists have regarded the onset of the oculocardiac reflex as a
      significant intraoperative problem, which is undermined by several case reports
      that describe dysrhythmias which have haved caused morbidity and death. Per
      definition the OCR is caused by ocular manipulation and involves intraoperative
      bradycardia by a change of 20 beats/minute compared to the preoperative heart
      rate or any dysrhythmia during the manipulation via a trigeminal-vagal-mediated
      reflex arc. Having operated on a 48-year-old, healthy woman in our clinic, who
      underwent a cardiac arrest during the blepharoplasty procedure, followed by a
      successful resuscitation, we investigated the onset of the OCR in our
      blepharoplasty patients within the last 3 years. The onset of the OCR was noted
      in 22 of 110 (20 %) blepharoplasty patients, mainly affecting younger, low
      weighted patients operated under local anaesthesia. Awareness and treatment of
      this potentially life-threatening oculocardiac reflex are necessary. In most
      cases the onset of the reflex may be avoided by a gentle operation technique and
      by refraining from severe traction to the muscle or fat pad. The best treatment
      of a profound bradycardia caused by the OCR is to release tension to the muscle
      or fat pad in order to permit the heart rate to return to normal. Intraoperative
      monitoring is of utmost importance.

PMID- 18716988
TI  - Autologous breast reconstruction following mastectomy.
AB  - The options for breast reconstruction following mastectomy have greatly expanded.
      Current techniques include pedicle flaps and free tissue transfers. With the
      advent of perforator flaps, additional options have become available that have
      the advantage of reduced donor site morbidity. The purpose of this manuscript is
      to review the most common methods of breast reconstruction using autologous
      tissues.

PMID- 18716989
TI  - Breast cancer local recurrence after breast reconstruction.
AB  - The primary aim of surgery in breast cancer is to achieve local control of
      disease. Secondly, improving quality of life and patient satisfaction is of
      utmost importance. While the positive effect of postmastectomy reconstruction on
      the psychological well-being of women with breast cancer has been demonstrated,
      evidence-based data on its oncological safety remain sparse. There is concern
      that the presence of autologous tissue or an implant may mask locoregional
      recurrence. Furthermore, there is little agreement on the appropriateness of
      routine radiological surveillance of these patients as well as on the surgical
      treatment of locoregional recurrence. We attempt to review the impact of breast
      reconstruction on the incidence and detection of locoregional recurrence and
      discuss treatment options.

PMID- 18716990
TI  - [Early-stage breast cancer - strategies for adjuvant systemic therapy].
AB  - Systemic adjuvant treatment is an integral component in the treatment of women
      with early-stage breast cancer and contributes significantly to the reduction of
      breast cancer-specific mortality. Decisions regarding adjuvant treatment
      modalities are becoming increasingly complex and demand individualised risk
      assessments based not only on clinicopathological criteria such as tumour size
      and axillary lymph node status but also on molecular predictors of the biological
      behaviour of the cancer. In addition, with the development of targeted therapies
      targeting HER-2 and with the availability of third generation aromatase
      inhibitors, new therapeutic options are available and need to be integrated into
      the treatment algorithms. In this review, we discuss the guidelines and
      recommendations concerning adjuvant systemic treatment of early-stage breast
      cancer based on current risk classifications.

PMID- 18716991
TI  - Primary versus secondary postmastectomy reconstruction.
AB  - Many patients who undergo a mastectomy desire breast reconstruction. The
      reconstructive surgeon must ensure that the patient has reasonable expectations
      and motives. While immediate breast reconstruction generally results in a more
      aesthetically pleasing breast, the primary consideration is treating the cancer.
      Immediate breast reconstruction has not been shown to affect the oncologic
      outcome; however, the reconstructive surgeon should confer with other treatment
      team members to obtain a clear understanding of the stage of cancer and any
      necessary adjuvant treatments. The likelihood of tumor recurrence, extent of
      excision required, and need for postoperative radiation, as well as psychosocial
      and financial considerations, may affect whether immediate or delayed
      reconstruction is appropriate.

PMID- 18716992
TI  - Loop mediated isothermal amplification (LAMP): a new generation of innovative
      gene amplification technique; perspectives in clinical diagnosis of infectious
      diseases.
AB  - Loop mediated isothermal amplification (LAMP) is a powerful innovative gene
      amplification technique emerging as a simple rapid diagnostic tool for early
      detection and identification of microbial diseases. The whole procedure is very
      simple and rapid wherein the amplification can be completed in less than 1 h
      under isothermal conditions employing a set of six specially designed primers
      spanning eight distinct sequences of a target gene, by incubating all the
      reagents in a single tube. Gene amplification products can be detected by agarose
      gel electrophoresis as well as by real-time monitoring in an inexpensive
      turbidimeter. Gene copy number can also be quantified with the help of a standard
      curve generated from different concentrations of gene copy number plotted against
      time of positivity with the help of a real-time turbidimeter. Alternatively, gene
      amplification can be visualised by the naked eye either as turbidity or in the
      form of a colour change when SYBR Green I, a fluorescent dsDNA intercalating dye,
      is employed. LAMP does not require a thermal cycler and can be performed simply
      with a heating block and/or water bath. Considering the advantages of rapid
      amplification, simple operation and easy detection, LAMP has potential
      applications for clinical diagnosis as well as surveillance of infectious
      diseases in developing countries without requiring sophisticated equipment or
      skilled personnel.

PMID- 18716994
TI  - Genetic polymorphisms at HLA-A, -B, and -DRB1 loci in Han population of Xi'an
      city in China.
AB  - AIM: To determine genetic polymorphisms at human leukocyte antigen (HLA)-A, -B,
      and -DRB1 loci in Han population of Xi'an city in China. METHODS: Polymerase
      chain reaction-based reverse line-strip sequence specific oligonucleotide
      hybridization was used to determine the alleles of HLA-A, -B, and -DRB1 in 516
      unrelated, healthy individuals of Han population in Xi'an. Allele frequencies at
      HLA-A, -B, and -DRB1 loci were estimated by direct counting method. Haplotype
      frequencies were calculated from genotype data by expectation maximization.
      RESULTS: A total of 14 alleles of HLA-A, 33 alleles of HLA-B, and 13 alleles of
      HLA-DRB1 were found. The most common alleles were HLA-A*02 (28.39%), A*11
      (19.19%), and A*24 (16.28%); HLA-B*13 (11.05%), B*15 (B62: 9.30%), and B*51
      (8.53%); and HLA-DRB1*15 (17.15%), DRB1*09 (13.18%), and DRB1*04 (10.85%). The
      most common haplotypes of HLA-A-B-DRB1 haplotype were HLA-A*30-B*13-DRB1*07
      (3.93%), HLA-A*02-B*46-DRB1*09 (3.20%), and HLA-A*33-B*58-DRB1*17 (1.63%).
      CONCLUSION: The finding that the HLA loci are highly polymorphic in Han
      population of Xi'an City may be useful for population genetics, HLA-related
      studies, human identification, and paternity tests in forensic sciences.

PMID- 18716995
TI  - Health care and community-based interventions for war-traumatized people in
      Croatia: community-based study of service use and mental health.
AB  - AIM: To explore the use of health care and community-based services in war
      affected regions of Croatia and its relation to mental health. METHODS: A sample
      of 719 adults exposed to at least one war-related traumatic event were selected
      by random-walk technique from three Croatian counties and interviewed for socio
      demographic data, mental health status (Mini International Neuropsychiatric
      Interview), and service use (Matrix for the Assessment of Community and
      Healthcare Services) in the period from 1991 to 2006. Descriptive analysis of
      service use was performed. Relations between service use, current mental health,
      and recovery from posttraumatic stress disorder (PTSD) were analyzed using
      logistic regression models. RESULTS: The traumatized population used a wide range
      of health care and community-based services. Health care was the most frequently
      used service category, especially primary health care (92.5%), followed by
      accommodation support (57.9%), financial support (57.7%), and employment support
      (32.5%). Compared with participants without mental disorders, participants with
      current PTSD were more likely to use only legal support (odds ratio [OR], 2.15;
      95% confidence interval [CI], 1.15-3.99), while participants with other mental
      disorders were more likely to use social support and contacts (OR, 1.72; 95% CI,
      1.08-2.75). Receiving accommodation support (OR, 2.05; 95% CI, 1.03-4.06) was the
      only significant predictor of recovery from PTSD, while seeking legal support
      (OR, 0.28; 95% CI, 0.08-0.92) was related to slower recovery. CONCLUSION:
      Although a wide range of services were organized to help the traumatized
      population in Croatia, only the solution of housing issue significantly predicted
      recovery. The organization of help services should take into consideration the
      existing infrastructure and local specificities, and respect the needs of people
      in war-affected areas.

PMID- 18716996
TI  - Psychological problems in children of war veterans with posttraumatic stress
      disorder in Bosnia and Herzegovina: cross-sectional study.
AB  - AIM: To assess psychological problems in children as reported by their veteran
      fathers with war-related posttraumatic stress disorder (PTSD). METHOD: The study
      group consisted of 154 veterans with war-related PTSD who were treated at the
      Mostar University Hospital. The control group consisted of 77 veterans without
      war-related PTSD who were selected from veteran associations by the snowball
      method. General Demographic Questionnaire, the first and fourth module of the
      Harvard Trauma Questionnaire-Bosnia and Herzegovina version, and the
      Questionnaire on Developmental, Emotional, and Behavioral Problems in Children,
      created specifically for the needs of this study, were used to collect data on
      veterans' perception of psychological problems in their children. RESULTS: In
      comparison with veterans without PTSD, veterans with PTSD reported significantly
      more developmental (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.51
      3.73), behavioral (OR, 3.92; 95% CI, 1.53-10.03), and emotional problems (OR,
      17.74; 95% CI, 2.40-131.10) in their children. CONCLUSION: Veterans with war
      related PTSD more often reported developmental problems in their children.
      Father's PTSD may have long-term and long-lasting consequences on the child's
      personality.

PMID- 18716993
TI  - Psychopharmacotherapy of posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) is a psychiatric disorder that develops
      after a psychological trauma usually caused by a situation perceived as deeply
      threatening to a person's life or integrity. Complex neurobiological changes
      triggered by such a traumatic and stressful experience may explain a wide range
      of PTSD symptoms and provide the rationale for psychopharmacological treatment.
      Selective serotonin-reuptake inhibitors make the first-line treatment of PTSD.
      Clinical experience has shown that they are more effective than noradrenalin
      reuptake inhibitors or tricyclic antidepressants. Antipsychotic drugs, especially
      atypical ones, have been shown effective in PTSD patients with psychotic
      characteristics or refractoriness to other treatments. Mood stabilizers seem to
      reduce mostly autonomous overreactions to stress, whereas the evidence for
      effectiveness of monoamine oxidase inhibitors is largely inconclusive. Other
      groups of medications, such as serotonin agonists and antagonists, new
      antidepressants, dual inhibitors of serotonin- and noradrenalin-reuptake,
      anticonvulsants, and opiate antagonists are also sometimes used in PTSD
      treatment. However, as shown in the present review, most clinical studies
      performed to date to investigate the effectiveness of different
      psychopharmacological agents in the therapy of PTSD have serious limitations in
      terms of small sample size, lack of blinding and randomization, and small effect
      size. More rigorously designed, comparative studies are needed to determine the
      usefulness, efficacy, tolerability, and safety of particular psychopharmaceutical
      drugs in the treatment of this therapeutically and functionally challenging
      disorder.

PMID- 18716997
TI  - Sexual functioning in war veterans with posttraumatic stress disorder.
AB  - AIM: To assess the sexual dysfunction among Croatian war veterans with combat
      related posttraumatic stress disorder (PTSD). METHOD: The study included two
      groups--101 war veterans with PTSD and 55 healthy control volunteers receiving
      outpatient general health care in several outpatient clinics in Split. tructured
      interviews on different aspects of sexual functioning were conducted from April
      to October 2007 by trained interviewers. RESULTS: Respondents with PTSD reported
      significantly less sexual activity during the previous month than controls
      (sexual fantasies 2.5+/-1.6 vs 3.7+/-1.7, P<0.001; foreplay 2.4+/-1.6 vs 3.5+/
      1.6, P<0.001; oral sex 1.6+/-1.2 vs 2.6+/-1.5, P<0.001; and sexual intercourse
      2.4+/-1.6 vs 3.8+/-1.5, P<0.001) on a 7-point Likert type scale (from 1--not a
      single time to 7--more times a day). As reasons for reduced sexual activities,
      respondents with PTSD more frequently than controls reported their own health
      problems (3.2+/-1.2 vs 1.5+/-0.8; P<0.001) or health problems of their partner
      (2.4+/-1.1 vs 1.9+/-1.1; P=0.004), whereas controls more frequently reported
      overwork than respondents with PTSD (2.6+/-1.1 vs 2.1+/-1.0; P=0.007) on a 5
      point Likert type scale (from 1--not a single time to 5--always). Respondents
      with PTSD reported antidepressant (n=52, 51%) or anxyolitics use (n=73, 72.3%).
      In a subgroup analysis, respondents with PTSD who were taking antidepressants
      masturbated less frequently than those who were not taking them (1.9+/-1.3 vs
      2.5+/-1.6; P=0.039), whereas premature ejaculation was more often experienced by
      respondents with PTSD who were not taking antidepressants than by those who were
      taking them (3.5+/-1.8 vs 2.7+/-1.5; P<0.049) both on a 7-point Likert type scale
      (from 1--not a single time to 7--more times a day). Conclusion. War veterans with
      PTSD had less sexual activity, hypoactive sexual desire, and erectile
      difficulties. Antidepressant therapy in veterans with PTSD may be associated with
      hypoactive sexual desire.

PMID- 18716998
TI  - Changes in plasma lipid concentrations and risk of coronary artery disease in
      army veterans suffering from chronic posttraumatic stress disorder.
AB  - AIM: To test the differences in serum lipid concentrations between veterans with
      chronic posttraumatic stress disorder (PTSD) and veterans without PTSD. METHODS:
      We determined plasma lipid parameters and calculated risk factors for 50 veterans
      in the PTSD group and 50 veterans in the non-PTSD group. Trauma exposure, coping
      strategies, and quality of life were assessed with Life Stressor List, Manchester
      Short Assessment of Quality of Life Scale, and Folkman-Lazarus Coping Strategies
      Questionnaire. RESULTS: There was no difference between the groups in the
      exposure to combat trauma. PTSD group had significantly lover education than non
      PTSD group (10.6+/-1.8 vs 12.4+/-2.6 years, P=0.007) and lower monthly income per
      family member (euro67.8+/-51.3 vs euro281.9+/-208.2, P<0.001). PTSD group had
      significantly higher levels of all plasma lipid parameters (cholesterol: 6.54+/
      1.24 vs 5.40+/-1.09 mmol/L, P<0.001; triglycerides: 2.55+/-0.68 vs 1.73+/-0.77
      mmol/L, P<0.001; very low density lipoprotein-cholesterol: 1.14+/-0.32 vs 0.78+/
      0.35 mmol/L, P<0.001; low density lipoprotein-cholesterol: 4.49+/-1.06 vs 3.46+/
      0.93 mmol/L, P<0.001). High-density lipoprotein cholesterol concentration was
      significantly lower in PTSD group (0.96+/-0.18 vs 1.15+/-0.24 mmol/L, P<0.001).
      Established risk factor for arteriosclerosis (6.96+/-1.19 vs 4.71+/-0.88,
      P<0.001) and Adult Treatment Panel III ten years risk for coronary disease
      (19.44+/-7.27% vs 9.74+/-4.10%, P<0.001) were significantly higher in the PTSD
      group. Secondary traumatization was significantly more frequent in the PTSD group
      (3.8+/-5.7 vs 1.3+/-4.7 events; P<0.001). CONCLUSIONS: Chronic PTSD is associated
      with dyslipidemia, leading to an increased risk of coronary artery disease.
      Environmental factors and coping strategies should be considered as important
      factors for the occurrence and persistence of PTSD.

PMID- 18717000
TI  - Bullying among school children in postwar bosnia and herzegovina: cross-sectional
      study.
AB  - AIM: To compare the prevalence and characteristics of bullying between two towns
      in Bosnia and Herzegovina-Stolac, which was exposed to firearm conflict during
      the 1992-1995 war in Bosnia and Herzegovina, and Posusje, which was outside of
      the active combat zone. METHODS: In this cross-sectional study, we included 484
      primary school pupils attending 4th-8th grade of elementary school, 217 (44.8%)
      of them from Stolac and 267 (55.2%) from Posusje. The pupils were interviewed
      using a standardized questionnaire on the experience of bullying. RESULTS: Every
      sixth pupil (16.4%) experienced at least one form of bullying almost every day,
      while 34 (7.0%) pupils constantly bullied other children. Sixth-eighth graders
      were more often bullies than 4th-5th graders (P=0.044). Girls were most often
      victims was of bullying, while boys were most often bullies (P=0.036). The
      expected difference in bullying between the two towns was not observed, except
      for older pupils in Posusje, who were more violent than their peers in Stolac
      (P=0.044). Among the analyzed variables of sex, age, town, and school
      achievement, only male sex was significant predictor of bullying (P=0.010),
      increasing the relative risk by 3.005 times. CONCLUSION: Bullying among primary
      school pupils did not differ between areas that experienced war activities in
      1992-1995. Our results could be useful in the introduction of specific prevention
      measures against bullying in postwar situation.

PMID- 18716999
TI  - Genome damage in oropharyngeal cancer patients treated by radiotherapy.
AB  - AIM: To estimate genome damage in oropharyngeal cancer patients before, during,
      and after radiotherapy and to measure the persistence of caused genome damage
      relevant in the evaluation of secondary cancer risk. METHODS: DNA damage was
      evaluated in peripheral blood lymphocytes of 10 oropharyngeal cancer patients
      using alkaline comet assay, analysis of structural chromosome aberrations, and
      micronucleus assay. Blood samples were taken 2 hours before irradiation on day 1
      of the first radiotherapy cycle, 2 hours after the application of the first dose,
      in the middle of the radiotherapy cycle, within 2 hours after the last received
      radiotherapy dose, and after 6 and 12 months after radiotherapy. RESULTS: In most
      participants, the highest level of primary DNA damage was recorded in blood
      samples collected after the administration of first radiation dose (mean tail
      length 25.04+/-6.23 mum). Most patients also had increased frequency of comets
      with long tail-nucleus (LTN comets) after the administration of the first
      radiation dose (mean, 10.50+/-7.71 per 100 comets), which remained increased in
      the middle of radiotherapy (mean, 18.30+/-27.62 per 100 comets). Later on, the
      levels of primary DNA damage as recorded by the comet assay, slightly diminished.
      The frequency of structural chromosome aberrations in lymphocytes gradually
      increased during the radiation cycle (26.50+/-27.72 per 100 metaphases at the end
      of the therapy), as well as the frequency of micronuclei (mean total number of
      micronuclei 167.20+/-35.69 per 1000 binuclear cells). CONCLUSION: Oropharyngeal
      cancer patients had relatively high levels of primary DNA damage in their
      peripheral blood lymphocytes even before therapy. The frequency of complex
      structural chromosome aberrations and the frequency of micronuclei increased with
      the progression of the radiation cycle and the doses delivered. As the frequency
      of chromosomal aberrations a year after radiotherapy mostly did not return to pre
      therapy values, it represents an important risk factor related to the onset of
      second cancer.

PMID- 18717002
TI  - Harassment in workplace among school teachers: development of a survey.
AB  - AIM: To develop a questionnaire on harassment in the workplace among teachers at
      primary and secondary schools. METHODS: We analyzed the existing questionnaires
      on harassment in the workplace and developed a new one was to specifically
      address harassment of teachers in the public education sector. The questionnaire
      was then experimentally applied to a sample of 764 primary and secondary school
      teachers in Split Dalmatia County, Croatia. It included three scales -exposure to
      harassment, witnessing harassment, and disturbance by harassment. Validity of the
      three scales was examined by factor analysis. RESULTS: All three scales showed
      satisfactory metric characteristics: Cronbach alpha coefficient was 0.93 for
      exposure scale, 0.95 for witnessing scale, and 0.97 for disturbance scale. Out of
      764 teachers surveyed, 164 (22.4%) were exposed to and 192 (31.7%) witnessed
      different kinds of harassment in the previous 12 months. There were significantly
      more of those who experienced harassment as witnesses (chi(2)(1)=249.301;
      P<0.001) than as direct victims. Eighty-six teachers (11.5%) reported having
      psychological and 76 (10.1%) physical health problems caused by their work.
      Exclusion as a consequence of harassment disturbed women more than men
      (chi(2)(1)=5.27; P=0.022). Those who were exposed to harassment had significantly
      lower median age (42; range 23-68) than those who were not exposed (45; range 23
      65) (U=31401.50; z=2.129; P=0.033). CONCLUSION: The questionnaire registered wide
      spectrum of harassment types, indicating the need for continuous monitoring and
      systematic work on the prevention of these phenomena. The study showed that
      exposure to harassment is associated with age, indicating that younger teachers
      should be the target population for detection and prevention of workplace
      harassment.

PMID- 18717001
TI  - Psychometric properties of Croatian and Slovenian short form of oral health
      impact profile questionnaires.
AB  - AIM: To develop Croatian and Slovenian versions of the 14-item Oral Health Impact
      Profile (OHIP) Questionnaire. METHODS: The English original version of the OHIP
      questionnaire was translated into Croatian (OHIP-CRO14) and Slovenian (OHIP
      SVN14) language by a forward-backward translation method. The psychometric
      properties of the OHIP-CRO14 and OHIP-SVN14 were tested. Concurrent validity was
      tested on 623 subjects (193 Croatian and 430 Slovenian), test-retest reliability
      on 115 subjects (55 Croatian and 60 Slovenian), internal consistency on 678
      subjects (218 Croatian and 460 Slovenian), and responsiveness on 51 patients (21
      Croatian and 30 Slovenian) in demand of treatment (toothache). RESULTS:
      Concurrent validity was confirmed by the association between the OHIP summary
      scores and self-reported oral health (correlation coefficients ranged from 0.40
      to 0.60, P<0.001). Test-retest reliability showed high intraclass correlation
      (correlation coefficients, 0.79-0.94). Internal consistency showed high Cronbach
      alpha (0.77-0.91). Responsiveness was confirmed by a significant difference
      between the mean OHIP score at baseline and follow-up (P<0.001 for both Croatian
      and Slovenian patients) and high effect size in Croatian and Slovenian patients
      in demand of treatment (3.00 and 0.57, respectively). CONCLUSION: Psychometric
      properties of OHIP-CRO14 and OHIP-SVN14 render these instruments suitable for the
      assessment of Oral Health Related Quality of Life in Croatia and Slovenia.

PMID- 18717003
TI  - "Inclusive Working Life" in Norway--experience from "Models of Good Practice"
      enterprises.
AB  - AIM: To determine whether enterprises belonging to the Bank of Models of Good
      Practice were more successful than average Norwegian enterprises in the reduction
      of sickness absence, promotion of early return to work, and prevention of early
      retirement. METHODS: In 2004 we selected 86 enterprises with a total of
      approximately 90000 employees from the Inclusive Working Life (IWL) Bank of
      Models of Good Practice. One representative of workers and one of management from
      each enterprise received a questionnaire on the aims, organization, and the
      results of the IWL program by mail. Data on sickness absence, use of early
      retirement, and disability retirement in the 2000-2004 period were collected from
      the National Insurance Registry. Data on comparable enterprises were obtained
      from the National Bureau of Statistics. RESULTS: The response rate was 65%.
      Although the IWL campaign was directed at reducing sickness absence, preventing
      early retirement, and promoting employment of the functionally impaired, most
      attention was paid to reducing sickness absence. Sickness absence rate in Models
      of Good Practice enterprises (8.2%) was higher than in comparable enterprises
      that were not part of the Models of Good Practice (6.9%). Implementation of many
      IWL activities, empowerment and involvement of employees, and good cooperation
      with the occupational health service were associated with a lower rate of
      sickness absence. On average, 0.7% new employees per year received disability
      pension, which is a significantly lower percentage than expected on the basis of
      the rate of 1.3% per year in comparable enterprises. Frequent use of disability
      pensioning was associated with high rate of sickness absence and having many
      employees older than 50 years. On average, 0.4% employees per year received early
      retirement compensation, which was expected on the basis of national estimates.
      Frequent use of early retirement was associated with having many employees older
      than 50 years. CONCLUSION: Models of Good Practice enterprises had a higher than
      expected sickness absence rate. This indicates that it is difficult to identify
      Models of Good Practice enterprises and that they cannot be treated as role model
      enterprises. Good cooperation with the occupational health service and the
      empowerment and involvement of the employees is associated with a low sickness
      absence rate.

PMID- 18717004
TI  - Trends in contraceptive knowledge and use among adolescent married women in
      Malawi.

PMID- 18717005
TI  - Not waiting for godot: proactive efforts to find potential zoonotic agents.

PMID- 18717006
TI  - When you hear the whistle blow.

PMID- 18717007
TI  - Assessment of the nutritional status among residents in a Danish  nursing home -
      health effects of a formulated food and meal policy.
AB  - AIMS AND OBJECTIVES: To gain information about the effects of implementation of a
      written food and meal policy and to evaluate to what extent systematic
      nutritional assessment and intervention would result in weight stability among
      the residents. BACKGROUND: Studies have shown that aged residents living in
      institutions suffer from malnutrition or are at risk of malnutrition. Health
      policies have pointed out that more attention should be given to individualised
      nutritional care. Several techniques are available to identify malnourished
      nursing home residents, but very few studies have reported findings of studies
      based on systematic nutritional assessment. DESIGN AND METHODS: A quasi
      experimental study based on a time series design used the residents as their own
      controls. The study included all 20 residents who resided at the nursing home at
      baseline in September 2004. Five residents died during the study period (mean age
      84.4 years, range 62-91 years). Altogether 15 residents (75%) were assessed all
      five times during the study period. RESULTS: The proportion of weight-stable
      residents increased significantly over the study from 52.6% (CI 99%: 23.1-80.2)
      at baseline to 87.7% (p < 0.01) at the end of the study. The proportion of weight
      losers significantly decreased from 42% (CI 99%: 23.1-80.8) to 13.3% (p < 0.01).
      The weight ranges indicate substantial weight changes, but over time the weight
      ranges became narrower, indicating a tendency towards weight stability.
      CONCLUSIONS: Although the nursing home had a formulated food and meal policy,
      this study shows the importance of a regular nutritional assessment combined with
      an individualised care planning. Relevance to clinical practice. Regular weighing
      combined with individualised care planning results in weight stability in nursing
      home residents. Individualised approach for nutritional care led by a qualified
      nurse is just as important in nursing homes as it is in hospitals.

PMID- 18717008
TI  - Paroxysmal right-sided muscular flaccidity.

PMID- 18717010
TI  - [Violence against women, prevention, relationships, and coping behavior].

PMID- 18717009
TI  - Dr. Kalman T. Kovacs. Recipient of the 2007 Endocrine Pathology Society Lifetime
      Achievement Award.

PMID- 18717011
TI  - The respiratory quotient has little value in evaluating the state of feeding in
      burn patients.
AB  - The respiratory quotient (RQ) is frequently used to predict over or under feeding
      in burn patients. The purpose of our study was to evaluate the usefulness of RQ
      obtained from indirect calorimetry to assess feeding adequacy in pediatric burn
      Intensive Care Unit patients. We evaluated pediatric patients who received
      enteral nutrition by continuous duodenal tube feeding at a calculated goal rate
      in the burn intensive care unit from January 2003 to March 2006. RQ lower than
      0.85 indicated underfeeding and RQ greater than 1.0 indicated overfeeding. Actual
      energy intake was recorded and compared with the energy intake divided by
      measured resting energy expenditure. Underfeeding was defined as a nutritional
      regimen providing <90% of caloric requirement; appropriate feeding was provision
      of within +/-10% of caloric requirements and overfeeding was provision of >110%
      of caloric requirements. On the basis of regression analysis, there was no
      relationship between energy intake divided by measured resting energy expenditure
      and RQ (R2 = 0.0059). There was also no relationship between measured RQ and the
      degree of feeding (N = 222). RQ <0.85 as an indicator of underfeeding had a low
      sensitivity of 40% and specificity of 77%. RQ >1.0 as an indicator of overfeeding
      had a poor sensitivity of 23% and a specificity of 85%. The RQ, used in
      isolation, is a poor method to assess over or underfeeding. Future prospective
      studies are needed to determine the optimal methodology for the assessment of
      nutritional needs in children with burn injury.

PMID- 18717012
TI  - [Scleral buckling retinal detachment surgery and pneumatic retinopexy].

PMID- 18717013
TI  - High-resolution analysis of genomic profiles of hepatocellular carcinoma cells
      with differential osteopontin expression.
AB  - Overexpression of osteopontin (OPN) could contribute to tumorigenesis and
      metastasis in hepatocellular carcinoma (HCC). Previous studies have shown that
      OPN-positive cancer cells are often localized in the periphery of cancer nodules
      adjacent to stromal cells. To identify the difference in intratumor genomic
      aberration pattern between OPN-positive and OPN-negative HCC cells, we adopted
      microarray-based comparative genomic hybridization (array-CGH) to achieve high
      resolution analysis of genome-wide aberrations. Our present study indicates that,
      compared to OPN-negative cancer cells, OPN-positive cancer cells show much more
      amplification of chromosomal regions, including 4q13.1-q13.3, 4q21.23-q22.1 and
      13q32.1-q32.3. Some candidate tumor related genes, such as SMR3B, MUC7, EPHA5,
      SPP1 and CLDN10, were detected with over 1.5-fold amplification. Together, the
      intratumor genomic heterogeneity may suggest that OPN-positive cancer cells play
      a more important role in the development of HCC malignancy than their OPN
      negative counterparts.

PMID- 18717014
TI  - Contact tracing vital to prevent chlamydia reinfection.

PMID- 18717015
TI  - [Advisory report from the Health Council of the Netherlands to include human
      papillomavirus vaccination in the national immunisation programme for the
      prevention of cervical cancer].

PMID- 18717016
TI  - [New drugs; exenatide and sitagliptin].

PMID- 18717017
TI  - Results of a company designed evaluation of the SLIPA.

PMID- 18717018
TI  - Post-traumatic pulmonary and cerebral fat embolism.

PMID- 18717019
TI  - A modified Touhy needle for continuous plexus blockade.

PMID- 18717020
TI  - Better info for handoffs.

PMID- 18717021
TI  - Design a & construction. Mock-up lets patients, staff test new rooms before they
      are built.

PMID- 18717022
TI  - Advances in medical technology. Improving diabetes care.

PMID- 18717023
TI  - What to expect in the hospital.

PMID- 18717024
TI  - Fast-food cooking at home. Mexican food.

PMID- 18717025
TI  - Insulin therapy for type 2 diabetes. Getting started.

PMID- 18717026
TI  - Food scoring for better nutrition.

PMID- 18717027
TI  - Diabetes quiz. How much do you know about your pancreas?

PMID- 18717028
TI  - DPP-4 inhibitors. A new class of drugs for type 2 diabetes.

PMID- 18717029
TI  - Type 2 diabetes. Are we closer to knowing "why"?

PMID- 18717030
TI  - For parents. Type 1 Diabetes TrialNet. From early detection to possible
      prevention.

PMID- 18717031
TI  - Supermarket smarts. Beans, peas, and lentils.

PMID- 18717032
TI  - Diabetes resources. Finding help for kidney disease.

PMID- 18717033
TI  - State of emergency: public health laboratories and terrorism preparedness.

PMID- 18717034
TI  - What's up with SCHIP?

PMID- 18717035
TI  - Increasing the health care workforce.

PMID- 18717036
TI  - [Combined edema reducing therapy in the treatment of advanced lower limb
      lymphedema].
AB  - Combined edema reducing therapy is a recognized method of lymphedema treatment.
      However such therapy can be difficult to implement from methodological and
      logistic point of view in cases of advanced forms of lymphedema. The aim of the
      study was the presentation and discussion of intensive phase of combined
      treatment in patient with advanced primary lymphedema. MATERIAL AND METHODS:
      Therapy was conducted on 19 patients (27 limbs) with edema reducing therapy
      program. Procedures were conducted daily for 4-6 weeks in out-patient and in
      wards conditions. RESULTS: Intensive phase of treatment succeeded in 3870-15 330
      ml edema reduction, consisting of 48-65% of initial status. Chronic leg ulcers
      were healed completely in 2 patients. Ten patients underwent minor adverse events
      (AE), such as superficial skin ulceration (n = 2), popliteal fossa skin
      maceration (n = 2), neuropathic foot pain (n = 3) and skin scratches (n = 3).
      Modification of the treatment allowed the complete healing of AEs within 2-7
      days, but it produced significant delay in achievement of desired therapeutic
      result, In 2 cases it prolonged hospital stay for 7 days. CONCLUSIONS: 1.
      Combined edema reducing therapy is very efficient form of treatment in advanced
      primary lymphedema. 2. Intensive, 4-6 week, phase of the treatment allows 3.8 to
      15.3 1 edema reduction. 3. In our opinion this phase should be conducted only in
      specialized centers for proper final results achievement with adverse events
      minimization. 4. The main point of the therapy is a combination of appropriate
      forms of available treatment.

PMID- 18717037
TI  - [Cytokine assessment in untreated hepatitis C virus infected patients and during
      interferon alpha +ribavirine therapy].
AB  - Many articles concerning the hepatitis C virus (HCV) infection emphasize the role
      of cytokines Th1- and Th2-dependent. The aim of our study was to assess the
      changes in the concentration of cytokines (IL-2, IFN-gamma, IL-4, IL-10)
      determined by ELISA test in serum of HCV infected patients treated with
      interferon alpha (IFN-alpha) and ribavirine. RESULTS: The cytokine levels in HCV
      patients (n = 40) were similar to levels observed in healthy volunteers (p >
      0.05). During IFN-alpha and ribavirine therapy no statistically significant
      changes in cytokine levels were observed in patients who achieved sustained
      virological response (SVR) compared to unsuccessfully treated patients (p >
      0.05). CONCLUSIONS: 1. Serum is not useful compartment to determinate level of
      cytokines by ELISA method in chronic hepatitis C. 2. The measurement of cytokine
      levels using ELISA test was not confirmed to be useful in monitoring and
      assessment of the therapy results in HCV infected patients.

PMID- 18717038
TI  - [The application of transversostomy in colorectal cancer surgery].
AB  - Defunctioning stomas (ileostomy and transversostomy) are the most common methods
      of the decompression of distal digestive tract. The aim of this study was to
      assess the results of transverse loop colostomy in colorectal cancer patients.
      MATERIAL AND METHOD: Between 1998 and 2007, 119 patients with colorectal cancer
      underwent transversostomy. In 97 patients the colostomy was formed during the
      primary operation as a planned prevention from further complications (1st group)
      and in 22 previously operated patients due to postoperative complications as a
      second procedure (2nd group). RESULTS: In the study group, there were 2 deaths in
      the perioperative period due to the anastomosis leakage and the intraabdominal
      sepsis. Three patients required reconstructive operation because of the colostomy
      stenosis and further 3 due to colostomy prolapse. There were also several cases
      of superficial wound infection after termination of transversostomy. Almost 78
      patients in total had the restoration of digestive tract continuity performed,
      prevalently from the 1st group. CONCLUSIONS: 1. In our opinion transversostomy is
      an effective solution for the proximal faecal diversion especially at high risk
      of anastomosis insufficiency or with present anastomosis leak. 2. In our study
      group, the incidence of complications (such as: chyme loss or dyselectrolytemia)
      in patients with performed transversostomy was low, thus we find it recommendable
      for the colon decompression.

PMID- 18717039
TI  - [The functional status in patients with discopathy of the lumbar spine receiving
      only conservative therapy or operative therapy].
AB  - Discopathy of lumbar spine inevitably leads to decreased quality of life in
      patients. Decrease of the backbone dysfunction at the degree which makes leading
      a life close to the normal style of family, social and professional life
      impossible, is the key therapeutic task. Evaluation of the functional disability
      can be the objective method of evaluation of the treatment efficacy. The purpose
      of this study was to analyze of the functional state in patients with lumbar
      discopathy receiving either conservative therapy only or surgical treatment.
      MATERIAL AND METHODS: 665 patients aged between 16 and 76 years with discopathy
      at L4-L5, L5-S1 levels have been enrolled into the study. In analyzed group 348
      patients received only a conservative therapy whereas 317 patients underwent an
      operative procedure. Analysis has been performed based on four rating scores for
      evaluation of the functional status: Low Back Pain Rating Scale, Functional
      Economic Outcome Rating Scale of Prolo, Oswestry Low Back Pain Disability
      Questionnaire, Low-Back Outcome Score. RESULTS: In preliminary examination
      approx. 40% decrease in parameters of evaluation of the functional status has
      been found in the group of patients receiving conservative therapy. Functional
      status of the patients within more than 10-year period of treatment was
      sufficiently stable and tended to progression in distant study. Ability to
      perform daily life activities was the strongest determined by backbone and limb
      pains as well as by the level of neurological deficits. In preliminary
      examination approx. 45% decrease in parameters of evaluation of the functional
      status has been found in the group of operated patients. Functional status
      significantly improved within immediate period post surgery. CONCLUSIONS: 1.
      Functional status in patients with discopathy of the lumbar spine in basic degree
      is determined by neurological status and intensification of the pain afflictions.
      2. The operative intervention brings essential improvement of the patients'
      functional status. 3. Functional status deteriorates within subsequent years of
      the treatment; it is determined in greater degree by the age of patients than by
      treatment method.

PMID- 18717040
TI  - [Participation of metallo-beta-lactamases in resistance to imipenem and meropenem
      in clinical strains of Pseudomonas aeruginosa and Acinetobacter spp].
AB  - Imipenem and/or meropenem resistance has been observed commonly in nonfermenter
      species such as Pseudomonas aeruginosa (P. aeruginosa) and Acinetobacter spp. An
      increasing prevalence of carbapenems resistance mediated by acquired metallo-beta
      lactamases (MBLs) is being reported particularly for Gram-negative rods in
      several countries. The aim of this study was to determine participation of MBLs
      in resistance to carbapenems of P. aeruginosa and Acinetobacter spp. and
      antimicrobial susceptibility to antibiotics. MATERIAL AND METHODS: A total 79
      clinical strains of Gram-negative rods (P. aeruginosa and Acinetobacter spp.)
      with resistance to carbapenems (or reduced susceptibilities) were screen for
      ability to production of MBLs. Metallo-beta-lactamases were detected by using E
      test (IP/IPI). The antibiotic susceptibilities determined by two methods: disc
      diffusion and E-tests (only carbapenems). RESULTS: Three of 79 strains (3.8%)
      were MBLs-positive. All of MBLs-positive strains were characterized by
      multiresistance to tested antibiotics. Cefepime and gentamicin were the most
      active antibiotics. The results of susceptibility testing of MBLs-negative
      strains (carbapenems-resistant) showed the highest percentage of susceptibility
      to cefepime - 92.3% P. aeruginosa and 97.7% Acinetobacter spp.

PMID- 18717041
TI  - [Assessment of the physical development level of the pubescent girls based on the
      example of the schoolgirls from Konskie].
AB  - The aim of this study was to assess a level of physical development and nutrition
      condition of girls being in middle and late stage of sexual development. Body
      build in relation to maturational age was also assessed in those girls. MATERIAL
      AND METHODS: Somatometric and questionnaire data of 304 girls aged 13-18 years
      were collected in community of Konskie. Retrospective method was used to assess
      menarcheal age. RESULTS: Majority of examined girls were in normal level of
      nutrition (82%), but 14% indicated overweight or obesity. Mean menarcheal age
      accounted for 12.42 +/- 1.03 years. There was no socio-economical differences in
      menarche among girls. CONCLUSION: Present study confirmed differences in body
      build in girls associated with tempo of sexual maturation.

PMID- 18717042
TI  - Neuroendocrine tumors of the pancreas.
AB  - The neuroendocrine tumors (NET) of the pancreas are very rare lesions with
      frequency of about 3 to 10 per 1 000 000 inhabitants. The neuroendocrine tumors
      composes a heterogeneous group of tumors. The gastro-entero-pancreatic tumors
      (GEP) constitute 70% of all NET and 2% of all digestive system tumors. There have
      been several attempts to classify those lesions and since 2000 exists WHO
      classification which divides NET according to malignancy and histologic
      structure. The most often NET of the pancreas are insulinoma, gastrinoma,
      glucagonoma, somatostatinoma, VIPoma. There is a recommendation to assay hormonal
      activity, measure concentration of specific peptides, biogenic amines and
      hormones produced by NET cells to establish diagnosis. Those tests are useful in
      monitoring treatment and in prognostication course of the disease. Imaging
      methods especially useful in localization GEP-NET are: ultrasound (US),
      endoscopic ultrasound (EUS), somatostatin receptor scintigraphy (SRS), computer
      tomography (CT), magnetic resonance (MR) and angiography. The most sensitive
      method in preoperative diagnosis seems to be EUS or less accessible intra ductal
      ultrasonography (IDUS). Surgical treatment depends on progression of disease as
      well as on localization of tumor and consists in both radical methods and
      palliative operations. The gold standard in pharmacological treatment are
      somatostatin analogs which can induce long-term remission even in inoperable
      lesions. Although NET of pancreas are very rare. they are still important
      diagnostic and therapeutic problem and requires interdisciplinary co-operation.
      The neuroendocrine tumors should be treated in centers with highest rank of
      references.

PMID- 18717043
TI  - [The relationship between cigarette smoking and some types of idiopathic
      interstitial pneumonias].
AB  - Desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated
      interstitial lung disease (RB-ILD) and idiopathic pulmonary fibrosis (IPF) are
      the interstitial lung diseases of unknown etiology. Among patients with these
      disorders there is a prevalence of current or ex-smokers: over 90% in RB-ILD, 60
      90% in DIP and 41-83% in IPF. Thus, cigarette smoking is to be a risk factor of a
      great significance. In clinical practice a correct differential diagnosis between
      RB-ILD and DIP on one hand and IPF on the other one is very important. Both
      bronchoalveolar lavage fluid and lung biopsy specimen taken from RB-ILD and DIP
      patients contain increased proportion of dusty brown alveolar macrophages. On CT
      scans the extent of fibrosis and inflammation areas is rather low. Contrary to
      IPF the prognosis of RB-ILD and DIP is generally good. Most patients improve
      clinically and radiologically with smoking cessation and corticosteroids. Further
      attempts towards new facts regarding the relationship between cigarette smoking
      and the pathogenesis and clinical course of different types of interstitial lung
      diseases are still needed.

PMID- 18717044
TI  - [Restorative treatment of cervical tooth lesions in aspect of biomechanics].
AB  - The study describes an appropriate treatment approach to the cervical tooth
      lesions from biomechanical point of view. The occlusal loading plays an essential
      role in development and failure of restorative treatment of this kind of defects.
      Resulting from these loading the stresses and issuing strain accumulate just in
      cervical region of the teeth and they influence both the marginal adaptation and
      sealing of the restoration. The shear and tensile stresses are responsible for
      breaking the bonds between the tooth tissues and restoration, leading to its
      destruction. The state of stress is dependent, above all, on direction of loading
      forces and on E (the elasticity modulus of applied material). For cervical
      filling a flexible material should be chosen, characterized by the low E modulus,
      due to less injurious distribution of interfacial stresses. It is necessary to
      equilibrate occlusal contacts before all filling procedures. Elimination of
      lateral and oblique forces can be achieved by occlusal equilibration.

PMID- 18717045
TI  - [Questionnaire impact on participation and autonomy (IPA)].
AB  - There are many problems which can decrease the quality of life of disabled
      persons. It means either social condition, family life, education, vocational
      status, sport, recreation and psychological implications. The Impact on
      Participation and Autonomy Questionnaire (IPA) is a valid, reliable and
      acceptable measure of participation and autonomy in people with a range of
      conditions, especially with multiple sclerosis, spinal cord injury and rheumatoid
      arthritis. The psychometric properties of IPA are promising and indicate that IPA
      has potential to be developed further. Most respondents believe that the IPA
      items are easy or very easy to understand, relevant and not embarrassing. In
      review report the own translation of IPA into Polish language has been presented.

PMID- 18717046
TI  - [Quality of life in visual disturbances in multiple sclerosis].
AB  - In multiple sclerosis (MS) often the visual pathway is impaired. Very early
      symptom which precedes neurological signs is the retrobulbar optic neuritis. In
      MS patients near as well as distance, color and peripheral vision can be
      disturbed. Many patients are not aware of visual impairment which could cause the
      delay in diagnosis. The assessment of the visual field in patients with MS
      enables early diagnosing as well as monitoring of the course of the disease. In
      monitoring of the course of disease most important is the evaluation of quality
      of life. The assessment of quality of life in MS is well known, even better than
      in other neurological diseases. Less known is the question of quality of life
      diminished because of visual field defects in MS. In review report the value of
      perimetry in diagnosing MS, visual disturbances in MS and contemporary
      possibilities of evaluation of quality of life in MS patients including those
      with defects in visual field has been described. The VFQ-25 questionnaire is a
      sensitive and useful tool in self-assessing visual function in MS patients.

PMID- 18717047
TI  - [Reactive oxygen species in pathogenesis of central nervous system diseases].
AB  - Many recent studies have provided evidence that reactive oxygen species (ROS) and
      other free radicals are implicated in pathogenesis of various central nervous
      system (CNS) diseases. In this paper the formation of ROS, protective mechanisms,
      nonenzymatic and enzymatic antioxidative markers are presented as well as the
      role of ROS and oxidative stress in CNS diseases in children and in adult
      patients.

PMID- 18717048
TI  - [Variability in clinical expression of Noonan syndrome--the report of two
      familial cases].
AB  - Noonan syndrome (NS) belongs to one of the most frequent genetic disorders with
      autosomal dominant pattern of inheritance. The main symptoms of NS are short
      stature, congenital heart defects, thorax deformities and specific dysmorphic
      features: hypertelorism, low set ears. short and wide neck, wide spaced nipples.
      The clinical picture ofNS changes with the age, which impedes the proper
      diagnosis in adults. We present two familial cases of Noonan syndrome with
      mutated PTPN11 gene in probands and one of their parents and siblings. We
      analyzed clinical features with regards to NS diagnostic criteria.

PMID- 18717049
TI  - [Difficulties in the treatment of pathological mandibular fracture].
AB  - Mandibular fractures are some of the most frequently occurring injuries in the
      maxillofacial region although pathological fractures state only 2% of them. Bone
      cysts are common lesions of mandible and maxilla. Their long asymptomatic
      development causes extensive deformation and bone damage. A case report presents
      fracture of mandible affected with massive odontogenic cyst. Presentation,
      diagnosis and management of fracture and intraosseus pathology is discussed.

PMID- 18717050
TI  - Femoral hernia with acute appendicitis in a male patient.
AB  - In literature, the reports on femoral hernia with acute appendicitis are scarce.
      It is mostly encounter in elderly women than men patients. Due to the scarcity of
      reported cases, no standard treatment is defined. We report a case of acute
      appendicitis in femoral hernia in middle-aged man. RESULTS: The main symptoms of
      appendicitis in femoral hernia are similar to those of incarcerated hernia, with
      painful swelling in the groin, but the differential trait is asymptomatic
      abdomen. The final diagnosis is usually made intra-operatively. CONCLUSION: In
      view of the fact that femoral hernia itself is more frequently encountered in
      elderly women patients, the cases of appendicitis contained in the hernial sac
      refer mostly to this population. However, a possibility of this condition
      developing also in middle-aged men cannot be excluded. Early surgical treatment
      is the only option to handle the problem.

PMID- 18717051
TI  - A journey into the past--the history of thyroid surgery.
AB  - We present a short sketch of how the knowledge of thyroid surgery has evolved
      throughout decades with pointing out to prominent surgeons who achieved great
      deeds in the history of thyroidectomy. The progress of thyroid surgery is
      believed to be of utmost importance because it reflects evolution of surgery
      itself. Although surgeons of our days can rely on wide range of examinations,
      modern equipment and endocrinological support, they should remember the rules in
      medicine, that are obligatory nowadays, have been created throughout decades. The
      abridged sketch of the history of thyroidectomy reflects how long, difficult and-
      many a time--dramatic way was surmounted by notable and brave pioneers of
      endocrinological surgery and how they advanced the surgical treatment of the
      thyroid from the dark ages into the modern era.

PMID- 18717052
TI  - Use of adrenaline in allergy.

PMID- 18717053
TI  - Eosinophilic esophagitis: from the case report to the evidence.
AB  - Eosinophilic esophagitis (EE) is a rare disease characterized by esophageal
      symptoms and dense esophageal eosinophilic infiltrate, both of wich persist
      despite prolonged treatment with proton pump inhibitors. The pathogenesis is
      poorly understood, but there is an increasing body of clinical and basic evidence
      that EE is an immune-mediated disease triggered by both food and inhalant
      allergens. At present there is no consensus statement on the number of
      eosinophils requiredfor the diagnosis, but generally a number of 20 eosinophils
      per high power field is considered a significant cut-off point. Therapies
      considered to be effective in the treatment of EE include: specific elimination
      diets or elemental diets; either systemic or topical corticosteroids therapy; and
      therapy with a selective inhibitor of leukotriene D4 receptor.

PMID- 18717054
TI  - The wasp-horsefly syndrome.
AB  - Here are two cases of two male patients of 57 and 62 years of age, already known
      as allergic to stinging hymenoptera venom, who after a horsefly bite have
      presented a serious 3-4 degree-type Mueller classification systemic reaction. The
      diagnosis has been carried out clinically and after an accurate environmental
      anamnesis and along with prick tests and RAST, further specific entomological
      confirm. In literature the so called wasp-mosquito-syndrome has been indicated
      where hyaluronidase has been referred to as the cross allergen, between the
      hymenoptera venom and the mosquito saliva, which likely triggers the reaction. We
      believe that it is also possible to take into consideration a wasp-horsefly
      syndrome as well, supposing the increased risk of anaphylactic reactions to
      Tabanidae bites, relatively frequent in areas with animals and streams, in
      subjects sensitized to stinging hymenoptera. We also suggest the possibility that
      in these subjects some systemic reactions are due in fact to Tabanidae bites and
      not so much for the failure of a possible active ITS of stinging hymenoptera.

PMID- 18717055
TI  - Joint statement on FDA investigation of Singulair from the ACAAI and AAAAI.

PMID- 18717056
TI  - Clostridium perfringens toxin types from freshwater fishes in one water reservoir
      of Shandong Province of China, determined by PCR.
AB  - Four hundred and twenty intestinal content samples (not including intestinal
      tissues) of freshwater fishes (60 silver carps, 100 carps, 100 crucian carps, 60
      catfishes and 100 zaieuws) caught from one water reservoir were examined
      bacteriologically for the occurrence of C. perfringens. Isolates were examined by
      polymerase chain reaction (PCR) for genes encoding the four lethal toxins (alpha,
      beta, epsilon and iota) for classification into toxin types and for genes
      encoding enterotoxin and the novel beta2 toxin for further subclassification. C.
      perfringens could be isolated in 75 intestinal contents samples (17.9%) from
      freshwater fish including: 13 silver carps, 2 carps, 12 crucian carps, 40
      zaieuws, and 8 catfishes. In 75 isolates, 58 strains (77.3%) were C. perfringens
      toxin type C (alpha and beta toxin positive), 13 strains (17.3%) were toxin type
      A (alpha toxin positive) and 4 strains (5.3%) were toxin type B (alpha, beta and
      epsilon toxin positive). In addition, the gene encoding for beta2 toxin was found
      in 47 strains (62.7%) of all the isolates, seven from type A, two from type B,
      and 38 from type C. The gene encoding for enterotoxin was not found in any
      isolate. These amplified toxin gene fragment were cloned and sequenced and
      compared with reference strains, the identity varied from 98.15% to 99.29%. This
      is the first report of C. perfringens alpha, beta, epsilon, beta2 toxins in
      freshwater fish and of beta, epsilon toxins in fish in general, and is the first
      discovery that the beta2 toxin could be detected in strains of type B. The origin
      of this bacterium and its importance to human food poisoning in freshwater fish
      is discussed.

PMID- 18717057
TI  - [Bluetongue virus serotype 8 (BTV-8)-associated brain malformations in two
      calves].
AB  - Congenital brain malformations such as hydranencephaly as well as internal and
      external hydrocephalus combined with porencephaly were diagnosed in two calves
      which were born in spring 2008. In both calves bluetongue virus was detected by
      real-time PCR. Teratogenic pestiviruses were not found by serological, molecular
      or immunohistological methods. A causal relationship between the malformations
      and the bluetongue serotype 8 epidemic in 2007 has to be considered.

PMID- 18717058
TI  - [The problem of oral administration of antimicrobially effective substances.
      Experiences from Switzerland].
AB  - The oral medication of sick animals is very common and a very preserve therapy.
      This method of therapy demands a high level of know-how for the veterinarians and
      also for meet-producers relating to food safety and bacterial resistance. In the
      new ordinance on veterinary medicine in 2004 many aspects of production and
      application of medicated feed are regulated in the legislation. This ordinance
      pretends to control all technical equipments used for production, transport and
      application of medicated feed by a qualified person (QP) on farms. Important
      criteria are defined in the ordinance on veterinary medicines.

PMID- 18717059
TI  - [Veterinary drug legal situation for oral medication in animal facilities in
      Germany].
AB  - Oral medication of animal stocks can be administered via oral ready-to-use
      veterinary medicinal products or by using medicated feedingstuffs. The
      regulations contained in the German Drug Act (Arzneimittelgesetz - AMG) and the
      ordinances derived from the AMG are applicable to both types of medicinal
      product. The legal requirements relating to the manufacture, authorisation,
      marketing, dispensing and proper use of these medicinal products in respect of
      oral medication are dealt with in detail. Pursuant to Section 13 AMG, companies
      that manufacture medicated feedingstuffs require a manufacturing licence. To take
      into account the special features of these medicinal products, specific
      stipulations have been laid down regarding the manufacture and dispensing of
      medicated feedingstuffs by these companies. The use of medicated feedingstuffs is
      for various reasons in steep decline, while oral ready-to-use medicinal products
      are, according to reports on practice in the relevant sector, increasingly being
      used to treat animal stocks as well. When dispensing veterinary medicinal
      products, the veterinarian must comply with the state of the art and make sure
      that the animal keeper is able to use the drugs properly. In order to react to
      doubts regarding compliance with these legal requirements, recommendations for
      use of oral medication should be developed which provide veterinarians with an
      aid to assist them in deciding which type of drugs are most suited for the
      respective case, and what is to be complied with in their use. The
      recommendations for use are intended to facilitate the correct application of
      oral medication in respect of both types of veterinary medicinal product.

PMID- 18717060
TI  - [Problems with oral administration of antimicrobially effective substances in
      animals--the situation with poultry].
AB  - The most prevalent method of application of drugs under veterinary prescription
      including antimicrobials is the oral administration. This paper describes the
      three possible and legal ways of applying veterinary drugs to animals: --as feed
      medication in a specialized feed mill which must be registered according to
      Section 13 of our national medicinal act; --as powder for oral application and
      medication with the feed on the premises of the farm; --dissolved in the drinking
      water for the relevant flock. Drinking water application is by far the most
      relevant method of applying antimicrobials to poultry flocks, if medication is
      needed. The most prevalent systems for drinking water application in poultry
      flocks are technically described: header tanks or dose pumps. As far as dose
      pumps are concerned both systems: proportional dose pumps as well as electronic
      dose pumps are in use. With poultry the use of antimicrobials is based on
      clinical judgement of the flock, laboratory diagnosis, including bacterial
      isolation and sensitivity testing (wherever possible), medical knowledge and
      experience of the involved veterinarian, economic considerations, epidemiological
      background and information at the flock level. Responsible use of antimicrobials
      is a major topic which discriminates German poultry meat producers (e.g.
      Wiesenhof) from third world meat producers. One reason for the uncritical use of
      Antimicrobials can be the so called "vet hopping" which is practised with some
      other meat delivering animals. This is ruled out by the guidelines of the major
      German Poultry Meat producers. These companies organise regular meetings with
      their caretaking vets to find out if there is still use of antimicrobials with
      some of their contractors as alternative to good Hygiene and Biosecurity. Some
      Poultry Integrations have additional restrictions on the use of some critical
      antimicrobials like Fluorquinolones and Tetracyclines.

PMID- 18717061
TI  - Survey protocol for detecting chytridiomycosis in all Australian frog
      populations.
AB  - Spread of the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) has
      caused the decline and extinction of frogs, but the distribution of Bd is not
      completely known. This information is crucial to implementing appropriate
      quarantine strategies, preparing for outbreaks of chytridiomycosis due to
      introduction of Bd, and for directing conservation actions towards affected
      species. This survey protocol provides a simple and standard method for sampling
      all frog populations in Australia to maximise the chances of detecting Bd. In
      order to structure and prioritise the protocol, areas are divided by bioregion
      and frog species are allocated depending on the water bodies they utilize into 3
      groups representing different levels of risk of exposure to Bd. Sixty individuals
      per population need to be tested to achieve 95% certainty of detecting 1 positive
      frog, based on the minimum apparent prevalence of > or =5% in infected Australian
      frog populations and using a quantitative real-time TaqMan PCR test. The
      appropriate season to sample varies among bioregions and will ideally incorporate
      temperatures favourable for chytridiomycosis (e.g. maximum air temperatures
      generally <27 degrees C). Opportunistic collection and testing of sick frogs and
      tadpoles with abnormal mouth-parts should also be done to increase the
      probability of detecting Bd. The survey priorities in order are (1) threatened
      species that may have been exposed to Bd, (2) bioregions surrounding infected
      bioregions/ecological groups, and (3) species of frogs of unknown infection
      status in infected bioregions. Within these priority groups, sampling should
      first target ecological groups and species likely to be exposed to Bd, such as
      those associated with permanent water, and areas within bioregions that have high
      risk for Bd as indicated by climatic modelling. This protocol can be adapted for
      use in other countries and a standard protocol will enable comparison among
      amphibian populations globally.

PMID- 18717062
TI  - Prevalence of Panulirus argus Virus 1 (PaV1) and habitation patterns of healthy
      and diseased Caribbean spiny lobsters in shelter-limited habitats.
AB  - Caribbean spiny lobsters Panulirus argus are socially gregarious, preferring
      shelters harboring conspecifics over empty shelters. In laboratory trials,
      however, healthy lobsters strongly avoided shelters harboring lobsters infected
      with the highly pathogenic Panulirus argus Virus 1 (PaV1). Because PaV1 is
      transmitted by contact, this behavior may thwart its spread in wild lobsters. In
      a field experiment conducted from 1998 to 2002 in a shelter-poor reef lagoon
      (Puerto Morelos, Mexico), densities of juvenile P. argus increased significantly
      on sites enhanced with artificial shelters (casitas) but not on control sites.
      Because PaV1 emerged in this location during 2000, we reexamined these data to
      assess whether casitas could potentially increase transmission of PaV1. In 2001,
      PaV1 prevalence was 2.5% and the cohabitation level (percentage of healthy
      lobsters cohabiting with diseased lobsters) was similar between natural shelters
      (3.5%) and casitas (2.4 %). The relative lobster densities in casita sites and
      control sites did not change significantly before (1998-1999) or after (2001
      2002) the disease emergence. In late 2006, data from casita sites showed a
      significant increase in prevalence (10.9%) and cohabitation level (29.4%), but no
      significant changes in lobster density. In May 2006, casitas were deployed on
      shelter-poor sites within Chinchorro Bank, 260 km south of Puerto Morelos. In
      late 2006, prevalence and cohabitation level were 7.4 and 21.7%, respectively.
      Our results are inconclusive as to whether or not casitas increase PaV1
      transmission, but suggest that across shelter-poor habitats, lobsters make a
      trade-off between avoiding diseased conspecifics and avoiding predation risk.

PMID- 18717063
TI  - Nucleotide sequence of a Madagascar hepatopancreatic parvovirus (HPV) and
      comparison of genetic variation among geographic isolates.
AB  - A segment of Madagascar hepatopancreatic parvovirus (HPV) genomic sequence (5742
      nucleotides) was determined through PCR and direct sequencing. This nucleotide
      sequence was compared to isolates from Australia, Thailand, Korea, and Tanzania,
      and the mean distance was determined to be 17%. The Madagascar HPV is closest to
      the Tanzania isolate (12%), followed by isolates from Korea (15%), Australia
      (17%) and Thailand (20%). Analysis of the genomic structure revealed that this
      HPV sequence is comprised of one partial Left open reading frame (ORF) (349 amino
      acids, aa) and complete Mid (578 aa) and Right (820 aa) ORFs. The amino acid
      sequences of the 3 ORFs were compared among isolates. The Right ORF was found to
      have the highest variation with a mean distance of 24%. This was followed by the
      Left and Mid ORF with distances of 13 and 7%, respectively. A phylogenetic
      analysis based on the amino acid sequence of the Right ORF divides 7 HPV isolates
      into 3 well-separated groups: Korea, Thailand, and Australia. The Madagascar HPV
      clustered with the Korea and Tanzania isolates. In Madagascar, HPV has been
      detected by histological examination since the 1990s. PCR analysis of a recent
      (2007) sampling showed a 100% prevalence. HPV was also detected in Mozambique
      with a 100% prevalence. High (95%) prevalence of HPV was found in wild Penaeus
      merguinesis collected from New Caledonia. These results indicate that HPV
      displays a high degree of genetic diversity and is distributed worldwide among
      populations of penaeid shrimp.

PMID- 18717064
TI  - Comparisons among the complete genomes of four betanodavirus genotypes.
AB  - Betanodaviruses, the causative agents of viral nervous necrosis in marine fish,
      have bipartite positive-sense RNA genomes and have been classified (based on
      analysis of RNA2 sequences) into 4 genotypes: tiger puffer nervous necrosis virus
      (TPNNV), barfin flounder nervous necrosis virus (BFNNV), striped jack nervous
      necrosis virus (SJNNV), and redspotted grouper nervous necrosis virus (RGNNV).
      Full-length genomes of TPNNV and BFNNV were sequenced for the first time in this
      study. Their sequence data and those of SJNNV and RGNNV retrieved from GenBank
      were compared in order to investigate the relationships among the 4 genotypes.
      Between TPNNV and BFNNV, sequence identities were relatively high in RNA1 and
      encoded Protein A, but were not significantly high in RNA2 or the coat protein
      (CP). Similarly, between BFNNV and RGNNV, the amino acid sequences of CP were
      highly similar, but identities of RNA1, RNA2, and Protein A sequences were not
      especially high. Furthermore, multiple alignment data of the 4 genotypes of RNA2
      sequences revealed that the TPNNV and SJNNV sequences have the same sizes of gaps
      and extra sequences at the same positions. Collectively, these apparent
      contradictions in sequence identity suggest that betanodavirus genomes have been
      constructed via complex evolutionary processes.

PMID- 18717065
TI  - Recombinant infectious hematopoietic necrosis viruses induce protection for
      rainbow trout Oncorhynchus mykiss.
AB  - Infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicaemia
      virus (VHSV) are rhabdoviruses that infect salmonids, producing serious economic
      losses. Two recombinant IHN viruses were generated by reverse genetics. For one
      (rIHNV GFP) the IHNV NV gene was replaced with the green fluorescent protein
      (GFP) gene. In the other (rIHNV-Gvhsv GFP) the G gene was also exchanged for that
      of VHSV. No mortalities, external signs or histological lesions were observed in
      experimental infections conducted with the recombinant viruses. Neither the rIHNV
      GFP nor rIHNV-Gvhsv GFP was detected by RT-PCR in any of the examined tissues
      from experimentally infected fish. In order to assess their potential as vaccines
      against the wild type viruses, rainbow trout were vaccinated with the recombinant
      viruses by intraperitoneal injection and challenged 30 d later with virulent IHNV
      or VHSV. The GFP viruses provided protection against both wild type viruses. None
      of the recombinant viruses induced antibody production, and the expression of
      interferon (IFNalpha4) and interferon induced genes such as Mx protein and ISG-15
      was not different to that of controls. The rIHNV-Gvhsv GFP did not inhibit
      cellular apoptosis as it was observed in an IHNV inoculated fish cell line. These
      studies suggest that the recombinant rIHNV-Gvhsv GFP is a promising candidate as
      a live recombinant vaccine and also provides a good model to further study viral
      pathogenicity and the molecular basis of protection against these viral
      infections.

PMID- 18717066
TI  - Development of a sensitive and controlled real-time RT-PCR assay for viral
      haemorrhagic septicaemia virus (VHSV) in marine salmonid aquaculture.
AB  - A survey was undertaken to determine the potential distribution of viral
      haemorrhagic septicaemia virus (VHSV) in marine cage-based salmonid farms in
      Scotland. A rapid, accurate and sensitive quantitative real-time RT-PCR (qRT-PCR)
      assay was developed, targeting a conserved region of the nucleoprotein (N) gene
      of the virus. The qRT-PCR assay was shown to be more sensitive than the
      conventional VHSV RT-PCR. A validation protocol included several different virus
      isolates as the target and confirmed that the assay could detect all European
      VHSV genotypes (I, II and III). Both endogenous and exogenous controls were
      designed to control for integrity of template and distinguish between true VHSV
      positives and contamination with the positive control material. In total, the
      universal European VHSV qRT-PCR assay with exogenous positive control was applied
      to screen 2040 individual Atlantic salmon Salmo salar and 150 individual rainbow
      trout Oncorhynchus mykiss. No evidence of the presence of VHSV in association
      with either salmonid species in Scottish marine farms was detected. However, both
      marine Atlantic salmon and rainbow trout are still considered possible carriers
      of VHSV, which remains a potential threat to freshwater farming. Therefore, a
      continued surveillance of these species in marine environment is recommended.

PMID- 18717067
TI  - Epidemiology of squamous cell carcinomas in rudd Scardinius erythrophthalmus from
      SE Ireland.
AB  - An epidemiological study was carried out to investigate the possible aetiology of
      squamous cell carcinomas which occur in a population of rudd Scardinius
      erythrophthalmus (L.) from Lough Aderry in south-east Ireland. A total of 1343
      rudd were sampled from Lough Aderry and 2 nearby small lakes in spring, summer,
      autumn, and winter over 2 yr, 1986 to 1988. Fish were weighed, measured, sexed,
      aged, and examined for lesions. Water quality parameters and natural
      radioactivity were assessed as possible influencing factors in the disease. The
      prevalence of squamous cell carcinoma was 6.1% overall, with no significant
      difference between the lakes, seasons or years. Both male and female fish were
      affected, of ages from 1+ to 5+ yr. No fish of 6+ or 7+ yr was found with
      tumours, indicating that the neoplasm caused premature death. The female:male sex
      ratio of rudd with tumours was higher than that of healthy rudd overall,
      suggesting that males are more susceptible to the neoplasm. Of the parasites
      observed, Posthodiplostomum cuticola was common, but rarely found in rudd with
      tumours. Sphaerospora sp.was also common, but not in sufficient densities for
      statistical inference, and Argulus sp. was present on 7 fish. No viral particles
      were found. Natural radiation levels in the vicinity of the lakes were low. The
      lakes sampled are in an agricultural catchment, and the waters were eutrophic.
      While rudd are tolerant, it is likely that environmental conditions were
      stressful at least some of the time, with possible consequences for the
      immunocompetence of the rudd. The aetiology of the carcinoma is still unknown,
      but the possibilities of carcinogenic compounds resulting from the high nutrient
      levels, or of carcinogenic algal toxins produced during algal blooms, should be
      examined.

PMID- 18717068
TI  - Seasonality in the infection and invasion of Marteilioides chungmuensis in the
      Pacific oyster Crassostrea gigas.
AB  - The protozoan parasite Marteilioides chungmuensis causes irregular enlargement of
      the ovary in the Pacific oyster Crassostrea gigas. The parasite invades the
      oyster through the epithelial tissue of the labial palp, replicates in the
      connective tissue, and then moves to the gonad, producing spores inside the
      oocytes. In this study the seasonality and invasion period of the parasite into
      the host was investigated over a 1 yr cycle. Uninfected 1 and 0 yr old (spat)
      oysters were placed in an epizootic area every month from July 2004 to July 2005
      and September 2005 to March 2006, respectively, and left for 1 mo. Labial palps
      and gonad were sampled monthly and examined for infection by nested PCR and
      histological observations. Prevalence of infection detected by PCR was 70% or
      higher from August to October, but declined sharply in November and reached 7% or
      lower from February to April. To explain the low detection rate in winter, 1 yr
      old uninfected oysters were placed in an epizootic area in winter (water
      temperature: 8 to 10 degrees C) for 2 wk and then transferred to M. chungmuensis
      free seawater at 24 degrees C. Although prevalence of infection was ca. 7% before
      transfer to heated seawater, levels of 87% were detected after 1 wk. After a 3 wk
      exposure to heated seawater, parasites were found in host oocytes by histological
      observation. It was concluded that the low prevalence in winter was due to
      insufficient replication of M. chungmuensis at low seawater temperatures,
      resulting in levels not detectable by nested PCR, and not to the absence of
      invasion.

PMID- 18717069
TI  - Prevalence of microscopic tubercular lesions in freshwater ornamental fish
      exhibiting clinical signs of non-specific chronic disease.
AB  - A histopathological study of tubercular lesions in ornamental freshwater fish
      showing clinical signs of chronic sporadic disease was carried out using
      conventional and acid-fast staining. A total of 200 individuals of 38 species
      were examined for granulomatous lesions related to the occurrence of acid-fast
      bacteria. Tubercular lesions were found in 24 species. Systematic
      histopathological examination was used to assess the incidence of fish
      tuberculosis in aquaria.

PMID- 18717070
TI  - The state of our state.

PMID- 18717071
TI  - Emerging technology: coming to a mouth near you.

PMID- 18717072
TI  - Dentists helping dentists.

PMID- 18717073
TI  - Give your office a makeover. Use tax deductions to save money on equipment
      purchases.

PMID- 18717074
TI  - The most powerful management principle ever.

PMID- 18717075
TI  - Ever thought about going into the 'insurance business'?

PMID- 18717077
TI  - Tips to help you avoid the ER this summer.

PMID- 18717078
TI  - Dr. Harold Hillenbrand.

PMID- 18717080
TI  - What not to do to your teeth. Dentists name their patients' top 10 worst dental
      habits.

PMID- 18717081
TI  - A tangled web.

PMID- 18717082
TI  - On taking stock of our scholarly progress.

PMID- 18717083
TI  - Laser welding of removable partial denture frameworks.
AB  - PURPOSE: To identify and measure distortions inherent in the casting process of a
      Class III mandibular cobalt-chromium (Co-Cr) framework to illustrate the problems
      faced by the laboratory technician and the clinician and to measure the changes
      that occur during the correction of the fit discrepancy using laser welding.
      MATERIALS AND METHODS: Five identical castings of a Co-Cr alloy partial denture
      casting were made and measured between 3 widely separated points using the x, y,
      and z adjustments of a Nikon Measurescope. The same measurements were made after
      each of the following clinical and laboratory procedures: sprue removal,
      sectioning of the casting into 3 parts through the posterior meshwork, fitting
      the segments to the master cast, picking up the segments using resin, and laser
      welding of the 3 segments. RESULTS: Measurements of all 5 castings showed a cross
      arch decrease after sprue removal, an increase after fitting the segments to the
      master cast, and a slight decrease after resin pickup and laser welding.
      CONCLUSIONS: Within the limitations of this study, the findings suggest that
      precise tooth-frame relations can be established by resin pickup and laser
      welding of segments of Co-Cr removable partial denture frameworks.

PMID- 18717084
TI  - Relationship between the frequency of sleep bruxism and the prevalence of signs
      and symptoms of temporomandibular disorders in an adolescent population.
AB  - PURPOSE: The relationship between sleep bruxism (SB) and temporomandibular
      disorders (TMD) is unclear. This study aimed to estimate SB prevalence in an
      adolescent population and to investigate the relationship between SB frequency
      and prevalence of TMD signs/symptoms. MATERIALS AND METHODS: First-year students
      at a high school in Okayama, Japan, were recruited in 2005, with 195 subjects
      responding. The SB detection device was a miniature disposable device (BiteStrip,
      SLP) that indicated the total SB events per night on a 4-grade score. The
      subjects were divided into severe and nonsevere SB groups with SB frequency
      cutoffs. The subjects were examined for temporomandibular joint (TMJ) noise
      during mouth opening/closing, tenderness of the masticatory/cervical muscles, and
      range of TMJ condylar movement. The presence/absence of headache and shoulder
      stiffness was also determined by the interview. The odds ratio (OR) and
      confidence interval (CI) were calculated to test the relationship between SB
      frequency, gender difference, and presence of the TMD signs/symptoms by multiple
      regression analysis. RESULTS: Severe SB (more than 125 events per night) was
      significantly related to the presence of TMJ clicking (OR: 3.74, CI: 1.22-11.49,
      P = .02), while gender (male) was not related to the presence of TMJ clicking.
      Severe SB was not related to headache, though gender (male) was significantly
      related to headache (OR: 2.52, Cl: 1.04-6.11, P= .04) in these subjects.
      CONCLUSION: These results suggest that the presence of TMJ clicking was closely
      related to severe SB in an adolescent population.

PMID- 18717085
TI  - Influence of impression technique and material on the accuracy of multiple
      implant impressions.
AB  - This study aimed to analyze the influence of impression technique (pick-up versus
      reposition) and material on the accuracy of the working cast. Sixty impressions
      were made with 3 materials from a master cast with 4 XiVE implants. The changes
      in the implant axis direction, rotation, and 3-dimensional shift were assessed.
      The pick-up technique showed significantly (P < .05, U test) lower values for
      axis direction and 3D shift but higher values for rotation than the reposition
      technique. The differences between the materials were not significant (P > .05, H
      test). It can be concluded that the impression technique-in contrast to the
      impression material-has a significant influence on transfer accuracy.

PMID- 18717086
TI  - Implant prostheses and adjacent tooth migration: preliminary retrospective survey
      using 3-dimensional occlusal analysis.
AB  - Occlusal force analysis was retrospectively evaluated to clarify the proximal
      contact loss after fixed implant prosthesis placement. Twenty-eight patients (55
      prostheses) with fixed implant prostheses in the posterior region were divided
      into 2 groups: proximal contact loss and unchanged groups. The occlusal force and
      its distribution were 3-dimensionally measured using the Dental Prescale system.
      A high proportion of lingual and anterior component forces and high occlusal
      force distribution in the intercanine region were observed in the contact loss
      group. The high occlusal force of the adjacent tooth may enhance the mesial
      migration.

PMID- 18717087
TI  - Changes in occlusal force at denture dislodgement after refabrication or
      optimization of complete dentures.
AB  - The aim of this study was to evaluate the change in occlusal force at denture
      dislodgement (OFD) in patients with poorly fitting complete dentures after
      improvement. In 91 patients, OFD was recorded before treatment, immediately after
      fitting the renewed denture (direct effect), and 1 week, 1 month, and 6 months
      later (adaptation). OFD increased significantly (P < .01) after optimizing the
      dentures and was dependent on patients' gender and age. The greatest changes
      occurred within the first week. It can be concluded that the increase in OFD is
      not only induced by the optimized denture, but also-and to an even greater extent
      -by adaptation.

PMID- 18717088
TI  - Twenty-year follow-up of metal-ceramic single crowns: a retrospective study.
AB  - PURPOSE: The aim of this clinical retrospective study was to evaluate the
      survival and success of single metal-ceramic crowns after 20 years. The biologic
      and technical complications as well as patient satisfaction were recorded.
      MATERIALS AND METHODS: Fifty patients treated with 100 single metal-ceramic
      crowns attended the clinical 20-year follow-up examination. The mean follow-up
      time was 18.8 years (17.5 to 20.5 years). RESULTS: Twenty-one teeth with single
      crowns were extracted because of root fractures or esthetic or periodontal
      reasons. Ninety-seven percent of the subjects had no complaints about the
      esthetics of the crowns. The most common clinical findings were supragingival
      crown margins caused by gingival recessions, gingival bleeding on probing, and
      occlusal wear in opposing teeth. The success of the crowns after 20 years was
      75%, and the survival was 78%. CONCLUSION: In the 20-year follow-up of single
      metal-ceramic crowns, there were few biologic and technical complications, and
      patients were satisfied with the crowns. Crown removal was in most cases the
      result of root fractures in single crowns with endodontic posts.

PMID- 18717089
TI  - Three-year split-mouth randomized clinical comparison between crowns fabricated
      in a titanium-zirconium and a gold-palladium alloy.
AB  - PURPOSE: The aim of this study was to compare the clinical performance of metal
      ceramic crowns made with an experimental alloy prepared by the Nordic Institute
      of Dental Materials, containing 15% zirconium and 85% titanium (Ti-15% Zr), and a
      high noble gold-palladium alloy (Mattikraft). MATERIALS AND METHODS: Twenty
      patients who satisfied the inclusion criteria were selected sequentially from the
      departmental waiting list. Each patient received 2 crowns in the premolar or
      molar region. Which tooth was to receive a crown based on gold-palladium alloy or
      Ti-15% Zr alloy was randomly decided. A number of aspects indicating the clinical
      performance of the crowns were recorded at baseline and after 1, 2, and 3 years.
      RESULTS: No statistically significant differences between the 2 types of crowns
      were demonstrated regarding overall technical evaluation, occurrence of plaque,
      bleeding on probing, or patient satisfaction. Periodontal pocket measurements
      around Ti-15% Zr crowns were significantly higher than those around gold alloy
      crowns. However, a similar difference also existed at baseline. Periodontal
      pocket measurements increased and patient satisfaction improved significantly
      over time. CONCLUSIONS: Within the limitations of this study, the results
      indicate that there is no difference in the clinical performance of crowns based
      on Ti-15% Zr or gold-palladium alloy.

PMID- 18717090
TI  - Survival of abutment teeth used for telescopic abutment retainers in removable
      partial dentures.
AB  - This retrospective clinical study investigated the survival of 385 abutment teeth
      retaining 117 removable partial dentures with 3 types of telescopic abutment
      retainers. Within a mean service time of 6.26 years, 8.8% of 385 abutment teeth
      were extracted. Cox regression analysis revealed a significantly higher risk of
      tooth loss for posterior teeth (odds ratio: 2.985) and for teeth with root canal
      treatment (odds ratio: 3.298), whereas age, sex, and number and type of
      telescopic retainer had no influence on survival. Root canal-treated teeth did
      not show a higher fracture rate, excluding this as an explanation for an
      increased risk of tooth loss.

PMID- 18717091
TI  - Clinical parameters influencing the accuracy of 1- and 2-stage impressions: a
      randomized controlled trial.
AB  - PURPOSE: The clinical success of fixed restorations is linked to the precise
      reproduction of the prepared teeth by dental impressions. The hypothesis under
      examination was that neither clinical parameters nor the impression technique
      influenced the reproduction of the finishing line during impression making.
      MATERIALS AND METHODS: For 48 patients who needed a fixed restoration, a 1-stage
      putty-wash, 2-stage putty-wash, and monophase impression were made after
      preparation in a randomized order. Clinical parameters (Plaque Index, probing
      depth, bleeding on probing, Gingival Index, location of the finishing line,
      bleeding during impression taking, and blood at the impression) were recorded.
      Master casts were manufactured and optically digitized. Using the data of the 1
      stage putty-wash impression as reference, the reproduction of the finishing line
      was measured 3-dimensionally. Linear models were used for statistical analysis.
      RESULTS: The finishing line was reproduced most precisely by the 1-stage putty
      wash technique. Variables with significant influence were the impression
      technique, blood at the impression, and probing depth. The 2-stage putty-wash
      impressions showed significantly reduced accuracy compared with the 1-stage
      impressions. CONCLUSION: Clinical parameters and the impression techniques
      determine the reproduction of the finishing line. The benefit of 2-stage putty
      wash impressions with regard to a more complete rendering of subgingival
      finishing lines should be questioned in light of these results.

PMID- 18717092
TI  - Clinical studies of fiber posts: a literature review.
AB  - PURPOSE: This literature review aimed to find answers to relevant questions
      regarding the clinical outcome of endontically treated teeth restored with fiber
      posts. MATERIALS AND METHODS: All clinical studies published since 1990 in
      journals indexed in MEDLINE were retrieved by searching PubMed with the query
      terms "fiber posts and clinical studies." The reference list of the collected
      articles was also screened for further relevant citations. The strength of the
      evidence provided by the reviewed papers was assessed according to the criteria
      of evidence-based dentistry. RESULTS: Five randomized controlled trials (RCTs) on
      fiber posts have been published in peer-reviewed journals. A meta-analysis is not
      applicable to these studies since they do not address the same specific clinical
      question. Retrospective and prospective trials without controls are also
      available. CONCLUSIONS: Two RCTs indicate that fiber-reinforced composite posts
      outperform metal posts in the restoration of endontically treated teeth. However,
      this evidence cannot be considered as conclusive. Longer-term RCTs would be
      desirable. The placement of a fiber-reinforced composite post protects against
      failure, especially under conditions of extensive coronal destruction. The most
      common type of failure with fiber-reinforced composite posts is debonding.

PMID- 18717093
TI  - A review of functional outcomes related to prosthetic treatment after maxillary
      and mandibular reconstruction in patients with head and neck cancer.
AB  - PURPOSE: This review examined literature that reported functional outcomes across
      3 categories of prosthetic treatment after microvascular reconstruction of the
      maxilla and mandible: (1) conventional dental/tissue-supported prosthesis, (2)
      implant-retained prosthesis, and (3) no prosthesis. MATERIALS AND METHODS:
      Library databases were searched for articles related to reconstruction of the
      maxilla and mandible, and references of selected articles were hand searched.
      Relevant literature was identified and reviewed with criteria specified a priori.
      RESULTS: Forty-nine articles met the inclusion criteria. Twelve articles reported
      on function after maxillary reconstruction, with the majority of articles
      reporting on outcomes for 1 to 6 subjects. Thirty-nine articles reported on
      function after mandibular reconstruction. Speech outcomes were satisfactory
      across all groups. Swallowing reports indicated that many patients who received
      either type of prosthetic rehabilitation resumed a normal diet, whereas those
      without prosthetic rehabilitation were often restricted to liquid diets or
      feeding tubes. Patients without prosthetic rehabilitation reportedly had poor
      masticatory ability, whereas conventional prosthetic treatment allowed some
      recovery of mastication and implant-retained prosthetic treatment resulted in the
      most favorable masticatory outcomes. Quality-of-life outcomes were similar across
      all patients. CONCLUSIONS: Several limitations of the current literature
      prevented definitive conclusions from being reached within this review,
      especially regarding maxillary reconstruction. However, recognition of these
      limitations can direct functional assessment for the future.

PMID- 18717094
TI  - Prosthodontics: paradigms and practice.

PMID- 18717095
TI  - Evidence-based dentistry--it subdivided: accepted truths, once divided, may lack
      validity.

PMID- 18717096
TI  - Conflict of interest: the Achilles heel of evidence-based dentistry.

PMID- 18717097
TI  - Dental Olympians, 2008.

PMID- 18717098
TI  - Dental treatment, antibiotic cover and infective endocarditis: a major rethink.
AB  - The NICE Guidelines on Prophylaxis against Infective Endocarditis were published
      early this year. In this review, consideration is given to the evidence that the
      Working Party evaluated in arriving at their recommendations. CLINICAL RELEVANCE:
      The NICE Guidelines will have a very significant impact upon clinical practice.
      Antibiotic cover to prevent infective endocarditis prior to dental treatment has
      been a confusing and contentious issue. All members of the dental team should
      welcome these Guidelines which will impact upon the delivery of dental care to
      many categories of patient.

PMID- 18717099
TI  - Electrosurgery: a technique for achieving aesthetic and retentive resin-bonded
      bridges.
AB  - Resin-bonded bridges can provide an aesthetic option for fixed replacement of
      teeth. To achieve the appearance of a natural tooth, the pontic tooth must have
      the correct emergence profile. This paper describes the use of electrosurgery for
      tissue removal and ridge recontouring. The soft tissues overlying the edentulous
      ridge can be sculpted prior to resin-bonded bridge placement to improve the
      emergence profile of the pontic and the bridge's cleansability. Hyperplastic
      palatal gingival tissues can be excised to maximize bridge retainer coverage over
      the cingulum area. CLINICAL RELEVANCE: Electrosurgery may be of value in
      improving the appearance and retention of a resin-retained bridge.

PMID- 18717100
TI  - The Inman Aligner for anterior tooth alignment.
AB  - The Inman Aligner is a highly effective and unique evolution of the traditional
      spring retainer that uses super-elastic Nickel-Titanium open coil springs to move
      upper and lower anterior teeth with light but consistent forces, enabling
      correction of anterior crowding, rotations and some types of spacing. CLINICAL
      RELEVANCE: This article describes the appliance, its uses and limitations.

PMID- 18717101
TI  - Digital imaging: an update.
AB  - It is becoming increasingly common for orthodontists and dentists to capture and
      store their patients' clinical records in a digital format, including
      photographs, radiographs and even study models. It is useful to have an
      understanding of what these image files are composed of in order to be able to
      manipulate, store and display the images efficiently to best effect. CLINICAL
      RELEVANCE: Digital images are becoming a routine part of patients'clinical
      records and it is important to understand their make-up and how they can be saved
      and displayed.

PMID- 18717102
TI  - An update on digital photography for the general dental practitioner.
AB  - Digital photography technology has moved on dramatically in recent years, with
      photography in general becoming an even greater part of the social scene. The
      popularity of camera mobile phones and compact cameras have been major factors in
      the resurgence in the popularity of general photography. So, how has this revival
      and technological advancement affected dental photography? Understanding the
      equipment, and how to use it successfully, is still important, but many of the
      advancements have made life very much easier for the dental practitioner wanting
      to embrace this visual medium. CLINICAL RELEVANCE: This article will keep
      practitioners updated on the equipment available, and make the choice of
      equipment easier.

PMID- 18717103
TI  - How should we manage caries in deciduous teeth?
AB  - Recent research from the North of England has focused attention on the
      effectiveness of routine conservation of carious deciduous teeth. This has led to
      a debate within the profession stimulated by the belief that falling levels of
      restorative care equate to a failure of clinical care. The results from two major
      clinical studies suggest that the majority of carious deciduous teeth exfoliate
      without the child attending his/her dentist with pain and infection if left
      unrestored. In addition, it would appear that the conventional restoration of
      such teeth by general dental practitioners does not change the outcome. However,
      a study from Scotland suggests that untreated carious deciduous teeth increases
      the risk of sepsis, especially when many carious teeth are present. Further
      research is needed to help inform clinical decisions. CLINICAL RELEVANCE: This
      article addresses the central issue of the dental care of young children.

PMID- 18717104
TI  - Contemporary periodontal surgery: 1. Surgical principles.
AB  - Periodontal surgery comprises surgical intervention of the supporting tissues of
      the teeth. This ranges in complexity from simple exodontia to technically
      demanding periodontal plastic surgery and includes the management of periodontal
      diseases, implant placement and preparatory treatment for fixed and removable
      prostheses. Modern surgical management reflects both a move towards evidence
      based practice and the introduction of improved techniques and armamentarium.
      General principles of surgical management hold true regardless of what procedure
      is being carried out. These principles form a sound basis for any practitioner
      contemplating surgical interventions for their patients. CLINICAL RELEVANCE: A
      sound understanding of first principles will simplify periodontal surgical
      management. Careful surgical preparation will render surgical procedures more
      predictable and reduce post-operative discomfort.

PMID- 18717105
TI  - Critical appraisal: a template to evaluate scientific literature.
AB  - Medical educators have identified the need for clinicians to become lifelong
      learners; a large part of the drive for this continuum of education is derived
      from the research that demonstrates that knowledge and/or competence deteriorates
      with time following graduation and that this is caused by a failure to acquire
      new knowledge rather than a propensity to forget previously learned material.
      Clinicians therefore need to be trained to identify the relevant published
      literature and then to apply Critical Appraisal techniques to the articles
      acknowledged as being seminal to their professional development. CLINICAL
      RELEVANCE: Historically, Critical Appraisal has been inconsistently taught to
      both undergraduates and postgraduates. This short paper aims to give
      undergraduate students and practitioners a series of templates to use in order to
      evaluate scientific literature; it may be of use both within the wider aspect of
      dental practice and as a guide to answer questions within the context of
      educational assessment.

PMID- 18717107
TI  - The perils of dental tourism, closer to home.

PMID- 18717106
TI  - Atypical fulminating dental nfections.
AB  - Dental surgeons are faced with treating dental infections on a daily basis and
      the cases discussed in this paper highlight the potential outcome of such
      infections, especially in immunocompromised patients. Fulminating infection in
      the head and neck may present as a rapidly progressive, potentially fatal
      condition characterized by extensive necrosis of the subcutaneous tissues. One
      form of such infection is necrotizing fasciitis. Although first described in 1793
      by Pouteau, the term necrotizing fasciitis was first coined in 1952 by Wilson who
      noted that facial necrosis was the most consistent feature of this disease. When
      necrotizing fasciitis occurs in the head and neck region it is usually
      odontogenic in origin. This paper reviews the cases of four patients presenting
      with atypical fulminating dental infection who presented to the oral and
      maxillofacial department at Guy's and St Thomas's Hospital, London, resulting in
      cellulitis and necrotizing fasciitis. Aggressive management is critical for
      patient survival and time wasted is tissue lost. CLINICAL RELEVANCE: Early
      diagnosis and aggressive treatment of dental infections, especially in patients
      with altered immune status, is critical. There should be a high index of
      suspicion in patients with dental infections not responding to treatment and
      maxillary dental infections with sinus symptoms.

PMID- 18717108
TI  - Physical signs for the general dental practitioner. Case 56. A chemical facial
      peel using Alphahydroxy acid (AHA).

PMID- 18717109
TI  - Aspects of human disease. 24. Dementia.

PMID- 18717110
TI  - Hypercapnia effect on core cooling and shivering threshold during snow burial.
AB  - INTRODUCTION: Hypercapnia during avalanche burial may increase core temperature
      cooling rate by decreasing the temperature threshold for shivering or by
      increasing respiratory heat loss. METHODS: We studied the effect of hypercapnia
      on rectal core temperature (T(re)) cooling rate, respiratory heat loss, heat
      production, and the T(re) shivering threshold during snow burial (mean snow
      temperature -3.2 + 2.7 degrees C) in 11 subjects. In a 60-min hypercapnic burial
      subjects breathed a 5% carbon dioxide and 21% oxygen inhaled gas mixture and in a
      separate 60-min normocapnic burial subjects breathed ambient air. After
      extrication from snow burial subjects were passively rewarmed in a 15 degrees C
      shelter and T(re) afterdrop was measured. RESULTS: The deltaT(re) over 1 h of
      burial in the hypercapnic study was 1.28 +/- 0.4 degrees C and in the normocapnic
      study was 0.97 +/- 0.4 degrees C (P = 0.045). Minute ventilation, respiratory
      heat loss, total metabolic rate, and metabolic rate of the respiratory muscles
      were greater during the hypercapnic burial. There was no difference in shivering
      threshold between the hypercapnic and normocapnic conditions. Afterdrop in the
      hypercapnic study (0.69 +/- 0.4 degrees C at 21 +/- 8.1 min after extrication)
      was not different than in the normocapnic study (0.86 +/- 0.3 degrees C at 23.1
      +/- 5.3 min after extrication). In both the hypercapnic and normocapnic studies
      afterdrop cooling rate was significantly greater during extrication than during
      snow burial. DISCUSSION: Hypercapnia significantly increased T(re) cooling rate
      by increasing respiratory heat loss but did not suppress shivering. Afterdrop may
      significantly contribute to hypothermia during rescue of avalanche burial
      victims.

PMID- 18717111
TI  - Inspiratory impedance threshold device effects on hypotension in heat-stroked
      swine.
AB  - INTRODUCTION: Heat stroke is still an epidemiologically relevant disease with
      overall mortality rates as high as 15-33%. In heat stroke, hypotension is caused
      by relative central hypovolemia. We performed a feasibility study to determine if
      an inspiratory impedance threshold valve (ITDTM) set to open at -12 cm H2O would
      reverse systemic hypotension by enhancing venous return in hyperthermic,
      hypotensive, but spontaneously breathing animals. METHODS: Seven anesthetized
      pigs weighing 30 +/- 2 kg were warmed with a heating device until a mean rectal
      temperature of 44 degrees C was reached, and mean arterial blood pressure (MAP)
      was < or = 60 mmHg. The animals were then treated with the ITD. An intravenous
      bolus of 200 cc of 4 degrees C normal saline was delivered 20 min after the ITD
      was placed, and external cooling was started. RESULTS: Heat stroke criteria were
      achieved within 105 +/- 15 min. MAP had decreased from 105 +/- 5 to 57 +/- 5
      mmHg, and respiratory rates had increased from 33 +/- 2 to 101 +/- 13
      breaths/min. Addition of the ITD significantly improved MAP to 85 +/- 4 mmHg, and
      reduced respiratory rate to 54 +/- 6 breaths/min within 2 min. The effect was
      sustained until fluid replacement and external cooling were delivered 20 min
      later. At that point, MAP returned to baseline within 30 min, and 6/7 animals
      survived for an additional 30 min. CONCLUSIONS: Use of an inspiratory impedance
      threshold device resulted in an immediate rise in blood pressure in animals in
      heat stroke and preserved blood pressure for at least 20 min prior to cooling and
      fluid replacement.

PMID- 18717112
TI  - Intramuscular pressures in antigravity muscles using gravity-independent,
      pneumatic hardware.
AB  - INTRODUCTION: Resistive exercise helps prevent muscle atrophy in microgravity,
      but better exercise equipment is needed. Therefore, the purpose of this study was
      to determine if a pneumatic, gravity-independent leg-press device (LPD) provides
      sufficient force to leg musculature. We hypothesized that intramuscular pressure
      (IMP), a quantitative index of muscle force, is greater in the antigravity
      superficial posterior and deep posterior compartments than in the non-antigravity
      anterior compartment during bilateral leg-press exercise. METHODS: Millar
      pressure transducers were inserted into the anterior, lateral, superficial
      posterior, and deep posterior muscle compartments of the left leg of eight
      healthy subjects (three women, five men). Subjects were supine on the Keiser SX
      1, a pneumatic LPD. Then maximal voluntary contraction (MVC) was determined; each
      subject performed three consecutive voluntary contractions at approximately 18%,
      50%, and 100% MVC while continuously measuring IMP. Repeated measures ANOVA were
      used to determine differences of IMPs between compartments and loads. RESULTS:
      The magnitudes of IMP (mean +/- SEM) at 18 - 3% (abbreviated approximately 18%),
      50%, and 100% MVC in the superficial and deep posterior compartments were
      significantly greater than that in the anterior compartment during exercise (P <
      0.05). Additionally, IMPs in all four compartments significantly rose as
      resistance increased at approximately 18%, 50%, and 100% MVC (P < 0.05).
      CONCLUSION: The LPD provides significantly increased resistance to all four
      compartments, but with greater loading of the antigravity compartments as
      compared to the non-antigravity compartment. Since antigravity muscles of the leg
      are contained primarily in the superficial and deep posterior compartments, the
      LPD may help prevent muscle atrophy associated with microgravity.

PMID- 18717113
TI  - Fexofenadine effects on cognitive performance in aviators at ground level and
      simulated altitude.
AB  - INTRODUCTION: Antihistamines are used for the treatment of allergic rhinitis (AR)
      symptoms. However, the cognitive effects of some antihistamines can dramatically
      impair individuals in occupations that require sustained vigilance. METHODS: The
      cognitive effects of fexofenadine were compared to a placebo (passive control)
      and cetirizine (active control) in healthy naval flight personnel. All subjects
      received one dose of each treatment in one of six possible sequences with two
      washout periods in between, and were assessed for aviation-related cognitive
      skills using the Aeromedical Vigilance Test (AVT) at both ambient atmospheric
      conditions and normobaric hypoxic conditions. Drowsiness was self-assessed by
      participants using a visual analog scale (VAS). RESULTS: There was no significant
      difference between fexofenadine and placebo over the entire 60-min test period,
      under ambient atmospheric conditions, or under either hypoxic condition. Compared
      with placebo, cetirizine significantly increased AVT errors over the entire 60
      min test period, at 10,000 ft, and at 15,000 ft. No statistical difference was
      found between treatments under ambient atmospheric conditions, although
      cetirizine treatment resulted in a greater change from baseline in adjusted
      average number of AVT errors (0.2124 +/- 0.06) than fexofenadine treatment
      (0.1989 +/- 0.07) and placebo (0.0745 +/- 0.07). Furthermore, at 10,000 ft there
      were significantly more AVT errors with cetirizine than with fexofenadine. There
      were no significant increases in self-reported drowsiness (VAS) for both
      cetirizine and fexofenadine compared with placebo. CONCLUSION: Fexofenadine is
      comparable to placebo in its effect on the cognitive skills important for
      piloting an aircraft, while cetirizine impairs cognition and may affect piloting
      ability.

PMID- 18717114
TI  - Blood platelet count and severity of decompression sickness in rats after a
      provocative dive.
AB  - INTRODUCTION: Previous animal studies reported that platelet count (PC) is
      decreased following decompression. Adherence and aggregation of platelets to the
      bubble surface has been demonstrated in severe decompression sickness (DCS). The
      present study was designed to clarify the relationship between post-dive platelet
      levels and the severity of DCS in a rat model. METHODS: A total of 57 male
      Sprague-Dawley rats were assigned to either one experimental group with a
      hyperbaric exposure (N = 22) or one control group (N = 27). Rats were compressed
      to 1000 kPa (90 msw) for 45 min while breathing air and decompressed to surface
      in 38 min with stops at 200, 160, and 130 kPa. Onset of neurological DCS and
      death time were recorded during a 120-min observation period after surfacing. In
      the control group, rats were maintained at atmospheric pressure in the same
      chamber for an equivalent period of time. Blood samples for PC were taken 30 min
      before and immediately after exposure in two groups. RESULTS: Blood PC after
      hyperbaric exposure had significantly decreased, whereas PC had increased in the
      control group. We found a correlation between % fall in PC and latency to death
      time. The platelet loss tended to decrease when fatal DCS was delayed. Rats
      suffering from severe DCS with a short latency to death presented a pronounced
      decline in platelets. DISCUSSION: The present study highlighted a relationship
      between the post-dive decrease in PC and DCS severity in rats. Platelet
      consumption could offer a new index for evaluating decompression stress.

PMID- 18717115
TI  - Voluntary respiratory control and cerebral blood flow velocity upon ice-water
      immersion.
AB  - INTRODUCTION: In non-habituated subjects, cold-shock response to cold-water
      immersion causes rapid reduction in cerebral blood flow velocity (approximately
      50%) due to hyperventilation, increasing risk of syncope, aspiration, and
      drowning. Adaptation to the response is possible, but requires several cold
      immersions. This study examines whether thorough instruction enables non
      habituated persons to attenuate the ventilatory component of cold-shock response.
      METHODS: There were nine volunteers (four women) who were lowered into a 0
      degrees C immersion tank for 60 s. Middle cerebral artery mean velocity (CBFV)
      was measured together with ventilatory parameters and heart rate before, during,
      and after immersion. RESULTS: Within seconds after immersion in ice-water, heart
      rate increased significantly from 95 +/- 8 to 126 +/- 7 bpm (mean +/- SEM).
      Immersion was associated with an elevation in respiratory rate (from 12 +/- 3 to
      21 +/- 5 breaths, min(-1)) and tidal volume (1022 +/- 142 to 1992 +/- 253 ml).
      Though end-tidal carbon dioxide tension decreased from 4.9 +/- 0.13 to 3.9 +/-
      0.21 kPa, CBFV was insignificantly reduced by 7 +/- 4% during immersion with a
      brief nadir of 21 +/- 4%. DISCUSSION: Even without prior cold-water experience,
      subjects were able to suppress reflex hyperventilation following ice-water
      immersion, maintaining the cerebral blood flow velocity at a level not associated
      with impaired consciousness. This study implies that those susceptible to
      accidental cold-water immersion could benefit from education in cold-shock
      response and the possibility of reducing the ventilatory response voluntarily.

PMID- 18717116
TI  - Acceleration tolerance at night with acute fatigue and stimulants.
AB  - INTRODUCTION: The impact of pharmacological agents on aviators concerns all
      flight surgeons. This study tested the related hypotheses that acute fatigue
      reduces +Gz tolerance and endurance, and that stimulants can partially reverse
      this impact. Additionally, the researchers attempted to develop a test battery
      sensitive enough to detect subtle differences in aviator cognition and
      performance among conditions. METHODS: To determine the effect of fatigue on +Gz
      tolerance and the impact of stimulant use, 10 male centrifuge subjects, mean age
      32, from Brooks City-Base, TX, were tested in a repeated measures study under
      five nighttime conditions following an average of 22 h of sustained wakefulness
      during their circadian nadir. Using a within-subject design, subjects received
      placebo, dextroamphetamine 10 mg, modafinil 200 mg, methylphenidate 10 mg, and
      pemoline 37.5 mg at night, and were tested during a daytime control session.
      Cognitive/performance tests were administered before each centrifuge run.
      RESULTS: No difference in +Gz tolerance or endurance was detected among
      conditions. The cognitive/performance tests also did not detect any differences.
      Subject perception that anti-G straining maneuver (AGSM) difficulty was greater
      during the night placebo condition than during the daytime control,
      methylphenidate and modafinil night conditions reached statistical significance
      (P = 0.005, 0.012, 0.022, respectively). DISCUSSION: Physiological changes during
      the circadian nadir following acute sleep deprivation do not appear to negatively
      impact +Gz tolerance. A standardized protocol sufficiently sensitive to detect
      subtle behavioral and performance effects would be useful to test and compare the
      effect of other pharmacological agents on aviators.

PMID- 18717117
TI  - Cardiovascular training effects in fighter pilots induced by occupational high G
      exposure.
AB  - INTRODUCTION: A fundamental difference in the cardiovascular response to
      acceleration between a group of fighter pilots (FP) and a group of non-pilots
      (NP) has been demonstrated previously. This study investigated the longitudinal
      effects of repetitive occupational +Gz exposure on the cardiovascular response to
      acceleration. METHODS: There were 6 FP and 6 NP subjects who underwent rapid +75
      degrees head-up tilt (HUT) on two separate occasions. The FP group were tested
      after a non-flying period of 5 wk (Test 1), and tested again after a period of
      repetitive exposure to high +Gz missions (Test 2). The NP group did not fly at
      all between Test 1 and Test 2. Mean arterial pressure (MAP), heart rate (HR),
      stroke volume (SV), and total peripheral resistance (TPR) were all determined non
      invasively. SV was determined using impedance cardiography and calculated via the
      Kubicek equation. For each variable, resting values and the response to tilt for
      both HUT tests within and between each group were compared. RESULTS: In the FP
      group, resting MAP was higher (86 mmHg) in Test 2 compared with Test 1 (78 mmHg).
      Between groups, FP resting MAP was only different from the NP resting MAP in Test
      2. The FP HR response to HUT increased significantly between the two tests.
      CONCLUSIONS: These findings suggest a +Gz-induced cardiovascular training effect
      in the FP group. Repetitive exposure to +Gz results in an increased resting MAP
      and an elevated HR response to tilt, which may provide benefits to operational
      fighter pilots.

PMID- 18717119
TI  - Visual analog scales for assessment of thermal perception in different
      environments.
AB  - INTRODUCTION: Subjective thermal perception in stable and dynamic environments
      has been measured primarily by categorical rating scales. At present, there is an
      increasing use of visual analog scales (VAS) to assess whole body and body region
      thermal perceptions in laboratory and other thermal environments. DISCUSSION: The
      rationale behind the use of VAS is that individuals are more accurate in
      conveying their subjective experience if they are not forced to make ratings
      according to numbers or categories. Unipolar scales have the advantage of
      focusing on a single subjective perception, such as the amount of cold the
      subject experiences. With bipolar scales (e.g., cold to hot), the sensitivity in
      measuring the extent of a specific thermal experience may be diminished because
      the subject needs to make a discontinuous change from one thermal perception to
      another. CONCLUSIONS: The robust psychometric properties of VAS indicate their
      usefulness in measuring thermal experience. Unipolar VAS with a large equal
      interval scoring range will enable the investigator to measure small gradients of
      change in perceptual experience. However, the subjective perception of thermal
      status is not highly accurate at thermal extremes, and caution is needed in sole
      reliance on subjective report in these conditions.

PMID- 18717118
TI  - Individual, work-, and flight-related issues in F-16 pilots reporting neck pain.
AB  - INTRODUCTION: Neck pain is a common problem in F-16 pilots. A cross-sectional
      survey was used to determine the self-reported 1-yr prevalence of neck pain and
      to compare individual, work-related, and flight-related characteristics in F-16
      pilots with and without neck pain. METHOD: There were 90 male F-16 pilots of the
      Belgian Air Force and The Royal Netherlands Air Force who voluntarily completed
      an anonymous survey. RESULTS: The 1-yr prevalence of neck pain was 18.9%. Pilots
      were divided into two groups: healthy (HG) and neck pain group (NPG). This study
      could not identify individual or specific flight-related differences between
      these two groups. High force demands, often sitting for a long time, frequently
      holding the neck in a forward bent posture, and being physically tired were all
      physical work-related factors that were reported significantly more often in the
      NPG. The NPG also reported significantly more psychosocial factors, such as being
      mentally tired at the end of the day and being annoyed by others at the
      workplace. DISCUSSION: Since the specific flight-related factors were not
      significantly different between the HG and the NPG, physical and psychosocial
      factors could have been important factors in the development or maintenance of
      neck pain in F-16 pilots. CONCLUSION: The results of this study highlight for the
      first time that, in addition to flight-related issues, other aspects must be
      considered in analyzing neck pain. These other aspects stress the importance of a
      broader approach when considering neck pain, even in this population that is
      exposed to very high loads during flight.

PMID- 18717120
TI  - Plantar stimulation as a possible countermeasure to microgravity-induced
      neuromotor degradation.
AB  - Since the early days of human spaceflight it has been reported that extended
      exposure to gravitational unloading results in a myriad of neuromotor adaptations
      that, while appropriate for microgravity, are maladaptive upon return to Earth.
      If not countered, these adverse effects of microgravity can result in negative
      health consequences and place crewmembers at risk for injury. The most commonly
      used countermeasures in today's space programs are those requiring active
      participation in prescribed exercise regimes that are time intensive, not
      completely effective, and have led to relatively low compliance. In this paper we
      review evidence that suggests a "passive" countermeasure in the form of dynamic
      foot stimulation (DFS) to the plantar surfaces of the feet may be a useful
      supplement to more traditional exercise countermeasures. This includes reports
      from both Russian and American investigators using both human and animal models
      indicating the overall effectiveness of DFS, the specific stimulation parameters
      involved, and a physiological explanation for the outcomes associated with the
      exposure to microgravity. Additionally, the use of DFS has the potential to
      benefit those at risk for muscle atrophy, including those experiencing extended
      bedrest, the elderly, and those with spinal cord injuries.

PMID- 18717121
TI  - Acute lower limb ischemia associated with use of an immersion suit.
AB  - External compression is a rare cause of acute lower limb ischemia. Workers
      required to wear immersion suits during helicopter simulation training are
      exposed to external compressive forces which can alter the hemodynamics in
      arterial bypass conduits. Herein a case of arterial thromboembolization to the
      lower limb following the wearing of an immersion suit, in a patient who had
      undergone arterial bypass surgery 13 yr previously is presented. The potential
      for this episode of acute leg ischemia being a direct result of the compressive
      forces exerted by the immersion suit and the possible implications for wearers of
      immersion suits following arterial graft surgery is discussed.

PMID- 18717122
TI  - Decompression illness diagnosis and decompression study design.

PMID- 18717123
TI  - Oxygen on Everest: the development of modern open-circuit systems for
      mountaineers.
AB  - The use of supplemental oxygen on Mt. Everest is now commonplace. From 1990 to
      2006, more than 95% of those summiting the mountain did so using supplemental
      oxygen at some point during their ascent. The open circuit systems currently in
      use can be traced back to the device first used by George Finch on Mt. Everest in
      1922. Wearing equipment weighing 33 lb (15 kg), Finch and his colleague Geoffrey
      Bruce set a world altitude record by reaching a height of 27,250 ft (8175 m).
      However, it would be with a lighter system weighing just 22 lb (10 kg) that Sir
      Edmund Hillary and Tenzing Norgay made the first ascent of the mountain in 1953.
      In the years since then considerable improvements in weight, comfort, and
      efficiency have been made; however, the original "open" principles first used by
      Finch almost a century ago still remain steadfastly in place.

PMID- 18717124
TI  - You're the flight surgeon. Sinus barotrauma.

PMID- 18717125
TI  - Erythropoietin and HAPE.

PMID- 18717126
TI  - A recent advance in the objective quantification of operational fatigue: the
      Fatigue Science SleepBand program.

PMID- 18717127
TI  - Readers' perspective. The next administration should put far more government
      funds and resources behind the National Health Information Network.

PMID- 18717128
TI  - A new approach to public health data.

PMID- 18717129
TI  - The hospital as the network hub.

PMID- 18717130
TI  - The role document management will play in EHRs.

PMID- 18717131
TI  - I.T. helps ERs get connected.

PMID- 18717132
TI  - Mission: finding patient data.

PMID- 18717133
TI  - Is it worth the risk--serving as a beta test site?

PMID- 18717134
TI  - EHR a saint at volunteer practice.

PMID- 18717135
TI  - Easing the transfer of data.

PMID- 18717136
TI  - PHRs raise many issues.

PMID- 18717137
TI  - Characteristics of obese children aged 1-4 years at a referral clinic.
AB  - OBJECTIVE: To describe characteristics and indicators of nutritional status of
      young, obese children. STUDY DESIGN: Medical records of 135 children aged 1-4
      years seen in an urban referral setting between January 2000 and June 2006 were
      reviewed. Characteristics associated with severe obesity [percent ideal body
      weight (%IBW) > or = 160%] were determined. Relationships between %IBW, weight
      for-height Z score (WHZ), body mass index (BMI) and BMI Z score (BMIZ) were
      evaluated. Receiver operating characteristic analyses evaluated BMI values
      classifying severe and moderate (140-159% IBW) obesity. RESULTS: Children were:
      41% male, 71% Hispanic, 76% Medicaid/uninsured, 64% ever breastfed, had median
      BMI of 25.0 kg/m2 and median %IBW of 159. Fifty-two percent of mothers had BMI >
      or = 30 kg/m2. Severely obese children more frequently had an obese mother,
      birthweight > or = 4 kg, were older, male, never breastfed and reported higher
      juice intake. WHZ and BMIZ were lowest at 4 years; BMI and %IBW were lowest at 1
      year. %IBW and BMI were highly correlated. BMI > or = 22.2 kg/ m2 indicated
      moderate obesity (sensitivity = 0.90, specificity = 0.93), and BMI > or = 25.0
      kg/m2 indicated severe obesity (sensitivity = 0.97, specificity = 0.92).
      CONCLUSION: Few current health behaviors and many family or past risk factors
      were associated with degree of obesity. %IBW and BMI may be the most useful
      nutritional status measures to track progress in young, obese children.

PMID- 18717138
TI  - The impact of literacy enhancement on asthma-related outcomes among underserved
      children.
AB  - STATEMENT OF PROBLEM: Despite the availability of improved healthcare access,
      self-management programs, disease management protocols, and advances in
      pharmacologic and immunotherapy therapy, the prevalence of asthma in the urban
      inner city remains one of the major health disparities in the United States.
      Additionally, sustainability of effective intervention programs after the funding
      has ended remains a significant issue for asthma programs. OBJECTIVE: This study
      examines the effectiveness of a longitudinal intervention program that was
      designed with the assumption that improved literacy plays a role in improving
      asthma-related health outcomes among high-risk children with the most severe
      forms of asthma. METHODS: A longitudinal intervention over 6 months prospectively
      addressed the literacy and asthma self-management skills of 110 minority children
      in South Los Angeles utilizing weekly Saturday-school format. RESULTS: The
      results demonstrated that there was a statistically significant decrease in both
      hospitalization and emergency department (ED) visits during the intervention. In
      addition, all the children showed significant improvement in their reading level
      and self-efficacy. Multivariate logistic analysis demonstrated that enhanced self
      efficacy was directly related to decreased hospitalizations and ED visits.
      CONCLUSION: This intervention demonstrated that literacy enhancement is an
      important factor in improving self-efficacy and impacting asthma-related
      outcomes. Improved literacy is a sustainable factor that will not only improve
      asthma outcomes but will enhance the potential for educational success.

PMID- 18717139
TI  - Blood antioxidant parameters in sickle cell anemia patients in steady state.
AB  - Sickle cell anemia (SCA) is a hereditary disorder with higher potential for
      oxidative damage due to chronic redox imbalance in red cells. We measured
      antioxidant enzymes including catalase (CAT), glutathione peroxidase (GPx) and
      superoxide dismutase (SOD). We also determined oxidative damage of proteins in
      hemolysate of red blood cells (RBCs) and plasma (carbonyl assay). We
      characterized the membrane damage in terms of lipid peroxidation by accumulation
      of malonaldehyde (MDA) by HPLC in 30 healthy controls and 20 SCA patients in
      steady-state condition. Twenty (9 males/11 females) adult SCA patients and 30
      healthy controls were studied. All patients and control subjects had antioxidant
      (CAT, GPx, SOD, carbonyl and MDA) and hematological parameters done. Our data
      show that SCA patients had significant higher GPx and SOD activities than healthy
      controls. Carbonyl assay was noted in plasma but not in hemolysate. An enhanced
      production of MDA was observed in the serum of SCA patients. Our data support the
      growing evidence that patients with SCA are subjected to chronic oxidative stress
      and are able to oxidative damage in biological macromolecules such as proteins
      and lipids.

PMID- 18717140
TI  - The inner ear in patients with nasal allergy.
AB  - BACKGROUND: The endolymphatic sac has been proposed as a target organ responsible
      for inner-ear symptom in allergic subjects. This is a report of inner-ear
      symptoms in patients with nasal allergy. METHOD: Retrospective review of record
      charts of patients with known nasal allergy presenting to the otorhinolaryngology
      out-patient department of the University College Hospital, Ibadan in 5 years.
      RESULT: Ear symptoms were found in 95/144 (66%) subjects with nasal allergy. This
      comprises of 41 males and 44 females (M: F = 1:1). Of these, itching of the
      external ear canal, hearing loss and tinnitus accounted for 63 (66%), 55 (58%)
      and 39 (41%), respectively, while vertigo was found in 12 (13%). Peripheral
      vestibular signs of imbalance were seen in 11/95. The audiological assessment of
      73 subjects revealed normal pure-tone average in 43 (59%), and sensorineural
      hearing loss (SHL) in 17 (23.3%). The severity of SHL was mild in 6/17, moderate
      in 7 and moderate-to-severe in 4. The erythrocyte sedimentation rate (ESR) and C
      reactive protein (CRP) were elevated in 10/15 (67%) and 6/15 (40%), while the
      skin sensitivity test showed reactions to dust in 32, cold in 25, cockroach in 7,
      perfume in 11, vegetable oil in 1 and insecticide in 2. The clinical diagnoses
      were idiopathic tinnitus in 25 (26.3%), Idiopathic SHL in 17 (18%), cochlear
      hydrop in 6 (6%) and autoimmune inner-ear disease in 6 (6%). CONCLUSION: This
      report suggests some peculiar predisposition to inner-ear pathology in patients
      with nasal allergy. However a longitudinal assessment of cochleovestibular
      features of nasal allergy subjects will help in its validation.

PMID- 18717141
TI  - Pattern of rhabdomyosarcoma in Nigerian children.
AB  - BACKGROUND: Soft-tissue sarcomas are uncommon tumors that are infrequently seen
      in most surgical practices. They represent 6.5% of all cancers in children < 15
      years of age and are the fifth leading cause of cancer death in that age group.
      This study was conducted to show the prevalence and pattern of distribution of
      rhabdomyosarcoma among children in a black African population. METHODS: We
      retrospectively reviewed 232 cases of soft-tissue sarcomas that were managed for
      a period of 22 years (1985-2006). Materials were obtained from the clinical
      records, operation notes and histopathology reports of the patients. The records
      of patients with rhabdomyosarcoma were analyzed in details. RESULTS: The result
      showed the age peak incidence for the total soft-tissue sarcomas occurring
      between the third and sixth decades of life. Rhabdomyosarcoma constitutes 9.5% of
      the total number of patients managed, and 54.5% of these patients are age < 20
      years. CONCLUSION: We conclude that parents must be educated about the need to
      look out for any mass on their children that persists for > 4 weeks so as to
      reduce the delayed and advanced stage of presentation.

PMID- 18717142
TI  - Structural model analysis of HIV risk behaviors among sexually active minority
      adolescents.
AB  - Contents of this article are solely the responsibility of the authors and do not
      necessarily reflect the opinions, official policy or position of the U.S.
      Department of Health and Human Services, the Substance Abuse and Mental Health
      Services Administration or Centers for Mental Health Services and Substance Abuse
      Prevention. OBJECTIVE: To evaluate an HIV risk profile in sexually active black
      and Hispanic adolescents using a structural equation model (SEM). METHOD:
      Grantees from 15 states and Washington, DC, were selected to participate in the
      study. Black and Hispanic adolescents (N = 2,371) who completed the baseline
      instrument were required to have experienced vaginal, oral or anal sex in order
      to be included in this study. Total minority youths who self-reported as black
      but not Hispanic were n = 1,455 and for Hispanic n = 916. RESULTS: The
      hypothesized model fit moderately well (CFI = 0.940, TLI = 0.928, RMSEA = 0.039).
      The key significant direct effect was found (P < 0.05) for higher alcohol,
      tobacco and other drug use related to nonuse of condoms, more sex partners and
      use of substances before sex. CONCLUSION: Current findings underscore the need to
      incorporate culturally sensitive strategies in developing programs for minority
      youth. However, given that minority group members often report greater
      experiences of discrimination than whites, future research in this area should
      also include an examination of the role of other stressors such as racial
      disparities and their potential cumulative impact on minority youth and their
      risks for alcohol, tobacco and other drug use and HIV.

PMID- 18717143
TI  - Effect of partner relationship on motivation to use condoms among adolescent
      mothers.
AB  - PURPOSE: Adolescent mothers have high rates of repeat pregnancy and sexually
      transmitted infections (STIs). We sought to identify factors associated with
      their consistent condom use. METHODS: Data for 107 urban adolescent mothers
      enrolled in a longitudinal computer-assisted motivational interviewing (CAMI)
      intervention were analyzed. The intervention aimed to motivate and instill
      confidence in using condoms consistently. DATA SOURCES: 1) structured interviews
      during the third trimester of pregnancy (baseline), 2) CAMI responses at 9-12
      months postpartum. Outcomes were dichotomized as: consistent condom users and
      inconsistent condom users. RESULTS: At baseline, mean age was 17 (1.1 SD) years,
      96% African American, and 26% reported always using condoms. At 9-12 months
      postpartum, 33 (31%) used condoms consistently. Consistent condom users were less
      likely to report having sex with their baby's father (61% vs. 81%; p = 0.05).
      Adolescent mothers who used condoms consistently experienced greater self
      efficacy in the prevention of STIs and recognized the importance of preventing
      STIs with a new boyfriend (p = 0.006). Consistent condom users held the opinion
      that it was more important to use condoms with a new boyfriend than with their
      baby's father regardless whether their main partner was the father of their baby
      or a new boyfriend. CONCLUSIONS: Level of motivation, belief in the importance of
      condom use and self-efficacy to use condoms with a new boyfriend regardless of
      actual sexual partner relationship were the strongest predictors of consistent
      condom use among adolescent mothers. Future interventions aimed at improving
      condom use should focus on motivation and to different views held by teens
      regarding their partner-specific condom use.

PMID- 18717145
TI  - Ventricular fibrillation in a 5-year-old child on therapeutic dose of quinine
      dihydrochloride infusion for acute malaria.
AB  - Malaria is no doubt a disease of public health significance in the tropics.
      Plasmodium falciparum, resistant to the majority of the first-line antimalarial
      drugs, now causes most of the infections treated in sub-Saharan Africa. Although
      there is increasing use of artemisinin-based combination therapy in many African
      nations, quinine still remains a commonly used drug for severe and chloroquine
      resistant malaria. Cardiotoxicity associated with quinine has been largely
      reported. However, this was often more common with toxic doses. This case report
      is on a 5-year-old African Nigerian who was undergoing treatment for
      uncomplicated malaria with quinine dihydrochloride infusion. All the laboratory
      investigations done were within normal limits except for positive blood films for
      malarial parasites. However, pretreatment electrocardiographic evaluation of the
      patient was not carried out. She developed ventricular fibrillation and died <
      1.5 hours into the quinine infusion.

PMID- 18717144
TI  - Building protective factors to offset sexually risky behaviors among black
      youths: a randomized control trial.
AB  - OBJECTIVES: To test the effectiveness of the CHAMP among black South Africans in
      KwaZulu-Natal, South Africa. METHODS: A randomized control trial was conducted in
      KwaDedangendlale, South Africa, among youths (ages 9-13) and their families (245
      intervention families rearing 281 children and 233 control families rearing 298
      children). The CHAMPSA intervention targeted HIV risk behaviors by strengthening
      family relationship processes as well as targeting peer influences through
      enhancing social problem solving and peer negotiation skills for youths. RESULTS:
      Among caregivers in the control and experimental conditions, significant
      intervention group differences were revealed regarding HIV transmission
      knowledge, less stigma toward HIV-infected people, caregiver monitoring-family
      rules, caregiver communication comfort, caregiver communication frequency and
      social networks. Among youths, data revealed that control and experimental groups
      were significantly different for children in AIDS transmission knowledge and less
      stigma toward HIV-infected people. CONCLUSIONS: CHAMPSA enhances a significant
      number individual, family and community protective factors that can help youths
      avoid risky behaviors leading to HIV-positive status.

PMID- 18717147
TI  - Poisoning necessitating pediatric ICU admissions: size of pupils does matter.
AB  - INTRODUCTION: Childhood poisonings are common, but usually trivial, and
      infrequently necessitate intensive care unit (ICU) admissions. METHODS: A
      retrospective record review was conducted to analyze the pattern of severe
      poisoning-associated ICU admissions at a teaching hospital between May 2002 and
      December 2007. RESULTS: Six cases (4 boys and 2 girls, aged 2 months to 11 years)
      of drug poisoning-associated ICU admissions were identified. Methadone was the
      culprit in 3 boys and 1 girl, resulting in respiratory failure, depressed
      conscious state and pinpoint pupils. As relevant exposure history was not
      immediately apparent, diagnosis at the emergency department was only made
      correctly in 2 patients. Phenobarbitone overdose occurred in 1 girl with past
      history of phenobarbitone overdose as a clue. She was also considered to have
      pinpoint pupils that were unresponsive to naloxone. Features consistent with
      cholinergic toxidrome, including small pupils, and increased secretion occurred
      in an infant fed with milk prepared with an herbal broth suspected to have been
      adulterated with a pesticide. Atropine as an antidote was used when the child was
      in the pediatric ICU. All children made an uneventful recovery following their
      short ICU stay. CONCLUSIONS: Life-threatening poisonings requiring ICU support
      can pose diagnostic difficulties and challenges to frontline medical officers at
      the emergency department. Children from all age groups can be affected. Prompt
      diagnosis is based on relevant history, careful clinical examination and a high
      index of suspicion in patients known to be at risk. The pupillary size and its
      reaction following treatment serves as an important diagnostic clue.

PMID- 18717148
TI  - An unusual case of febrile neutropenia: acute myeloid leukemia presenting as
      myeloid sarcoma of the spleen.
AB  - Differential diagnosis of a focal splenic lesion in the context of acute leukemia
      is quite challenging. A 58-year-old woman presented with a 3-day history of fever
      and abdominal pain. The results of hematological work-up were consistent with
      acute myeloblastic leukemia (M2, French-American-British classification). Being
      susceptible to infection in this leukemic patient with severe neutropenia, a
      diagnosis of splenic abscess was straightforward, plausibly supported by the
      radiographic findings. Despite empiric broad-spectrum antibiotic treatment,
      hyperleukocytosis with resultant pulmonary leukostasis supervened. Histological
      sections from ultrasound-guided percutaneous core-needle biopsy of the spleen
      confirmed the diagnosis of myeloid sarcoma. However, delayed leukemia-targeted
      therapy, unfortunately, resulted in catastrophic mortality. It should be
      addressed that, even with the advent of modern imaging modalities, there can be a
      diagnostic pitfall when managing solitary splenic lesion in acute leukemic
      patients without histological examination. Early recognition with prompt
      chemotherapeutic intervention can be life saving.

PMID- 18717149
TI  - Sickle cell anemia, left ventricular hypertrophy and T-wave alternans.

PMID- 18717150
TI  - Provider barriers to hydroxyurea use in adults with sickle cell disease: a survey
      of the Sickle Cell Disease Adult Provider Network.
AB  - The FDA approved hydroxyurea for use in adults with sickle cell disease (SCD) in
      1998. In 2002, the NHLBI published recommendations for the use of hydroxyurea in
      this patient population. The purpose of this study was to evaluate providers'
      awareness of the NHLBI recommendations regarding hydroxyurea prescribing, whether
      these recommendations have changed providers' practices and how these providers
      prescribed hydroxyurea. We chose to survey a select group of providers of care to
      adults with SCD, members of the Sickle Cell Adult Provider Network. The response
      rate was 47%. Eighty-one percent of respondents reported they had read the NHLBI
      recommendations on hydroxyurea use, and 76% of respondents agreed with the NHLBI
      recommendations. Only 45% of respondents to this survey reported that they
      prescribe hydroxyurea to every eligible patient. Black respondents reported a
      higher percentage of their eligible patients being on hydroxyurea than white
      respondents. Seventy-seven percent of respondents thought that hydroxyurea was
      effective or very effective in patients with SCD. Ninety-four percent of black
      versus 73% of white versus 40% of other race respondents thought that hydroxyurea
      was effective or very effective in SCD patients (p = 0.006). The results of this
      survey suggest that lack of awareness, agreement and belief in the benefits of
      hydroxyurea contributes to providers underprescribing hydroxyurea.

PMID- 18717151
TI  - Today's conflict of interest compliance challenge: how do we balance the
      commitment to integrity with the demand for innovation?
AB  - Beginning in the 1980s, the federal government encouraged institutional providers
      to collaborate with pharmaceutical companies, medical device manufacturers, and
      biotechnology ventures. The rationale underlying this public policy was that
      collaboration would accelerate the pace of innovation. More recently, the focus
      is on whether these collaborations create conflicts of interest that jeopardize
      the safety of subjects and the integrity of data. Various constituencies are
      calling for conflict of interest reform, while the demand for new diagnostic and
      therapeutic tools has never been greater. These competing messages have
      stakeholders questioning what to do. This article reviews recent developments in
      conflicts of interest reform and provides recommendations that institutions and
      industry can consider as they undertake to develop a scalable and flexible
      approach to enhancing their conflicts of interest infrastructure.

PMID- 18717152
TI  - Limited provider panels: their promise and problems in an individual health
      insurance market.
AB  - The cost of healthcare, and consequently of health insurance, continues to
      increase dramatically. A growing chorus calls for replacing the fundamental
      method by which people purchase insurance today--through their employers--with a
      system of individually acquired insurance. This article argues that changing how
      Americans purchase health insurance could change the dynamics between insurers
      and healthcare providers in a way that could favorably impact costs, primarily
      through reliance on highly limited provider networks. It examines the bases of
      legal obstacles to limited provider networks embedded in both statutory and case
      law and urges re-examination of those bases in light of changes in the
      distribution system of health insurance.

PMID- 18717153
TI  - IFTC v. Evanston: antitrust enforcement of hospital mergers receives a shot in
      the arm.
AB  - This article examines the Federal Trade Commission's Evanston decision and
      assesses its future impact on hospital merger analysis. In finding that a
      consummated merger of two Chicago-area hospitals violated the antitrust laws, the
      FTC analyzed the merger using a unilateral effects theory of anticompetitive
      harm. This theory entails examining the competitive impact on third-party payors
      as a result of the loss of competition between the merging hospitals, rather than
      the traditional market share and market structure data relied upon in earlier
      court decisions. After a detailed discussion of the Evanston decision and the
      history of hospital merger litigation leading up to it, the authors argue that
      while the Evanston decision indicates that the government will use unilateral
      effects analysis in challenging future hospital mergers, this analysis is fraught
      with litigation challenges. The government's next case will not have the benefit
      of a strong evidentiary record as in Evanston, thereby making it more difficult
      for the government to prove its unilateral effects theory.

PMID- 18717154
TI  - Medical devices: the obvious, the readily-accepted, and the surprising.
AB  - The Food and Drug Administration's (FDA or the Agency) interpretation of the
      definition of a medical device in the Federal Food, Drug, and Cosmetic Act is
      very broad. Thus, the Agency has authority to regulate most products that have a
      health purpose or affect a person's body as medical devices unless they are
      clearly drugs or biologics. The primary purposes of this article are to help
      executives, managers, attorneys, regulatory professionals, healthcare providers,
      and consumers: (1) identify products that are potentially medical devices; (2)
      determine whether FDA is likely to regulate them as medical devices; and (3) if
      so, determine the applicable premarket requirements, if any. This article
      discusses the statutory criteria of a product's intended use, technological
      characteristics, and mode of action, and shows how FDA applies these criteria to
      determine whether a product is a medical device. This article provides examples
      of the Agency's interpretation of the statutory definition of a medical device
      and shows how to analyze whether a product is an FDA-regulated medical device.

PMID- 18717155
TI  - Having your cake and eating it too--the (un)enforceability of releases on future
      qui tam claims.
AB  - The Department of Justice reports that the United States has recovered over
      twenty billion dollars in settlements and judgments since Congress substantially
      strengthened the False ClaimsAct in 1986. These recoveries have come
      disproportionately at the expense of the healthcare industry. This article will
      provide a working knowledge of the significant cases addressing the issue of the
      enforceability of releases on future qui tam claims, then proceed to provide
      strategies for protecting members of the healthcare industry from future
      whistleblower claims.

PMID- 18717156
TI  - Union organizing in assisted living.

PMID- 18717157
TI  - [Cognitive and symptom profiles in Asperger's disorder and high-functioning
      autism].

PMID- 18717158
TI  - [Risk factors of near-fatal deliberate self-harm behavior in self-cutting
      patients: a three-year follow-up study at a psychiatric clinic].
AB  - Non-fatal self-injurious behavior such as cutting oneself is often performed
      without suicidal intent to cope with emotional distress, although it is well
      known to have a close association with future suicidal behavior. However, it is
      unclear what kinds of clinical features are presented by such self-injuring
      patients with a higher suicidal tendency. In the present study, we conducted a
      three-year follow-up study of female self-injuring patients to examine the risk
      factors of "near-fatal" deliberate self-harm behavior (DSH). The subjects were 81
      female outpatients who had cut themselves at least once, and who had consulted a
      psychiatric clinic from June 2004 to July 2004. Initial assessments included
      traumatic life events, clinical features of self-cutting, histories of self
      poisoning, alcohol abuse (Alcohol Use Disorders Identification Test: AUDIT),
      impulsivity (Barratt Impulsiveness Scale, 11th version: BIS-11), symptoms of
      bulimia nervosa (Bulimia Investigatory Test, Edinburgh: BITE), dissociation
      (Adolescent Dissociative Experience Scale: ADES), Global Assessment of
      Functioning (GAF) score, and axis I diagnosis of DSM-IV (Diagnostic and
      Statistical Manual, 4th version). After three years, we investigated whether the
      subjects had committed fatal DSH during the follow-up term. We obtained
      information on fatal DSH from 67 subjects during the follow-up term. Fifteen of
      the 67 (22.4%) had committed near-fatal DSH at least once, and one subject
      committed suicide by fatal DSH. Monovariate analysis revealed that in the initial
      assessment, the subjects with near-fatal DSH episodes more frequently reported a
      history of victimization by rape in adulthood and a history of OTC (over-the
      counter) drug self-poisoning, and had higher scores on the BITE and AUDIT than
      those without near-fatal DSH episodes. Further, multivariate analysis
      demonstrated that only the BITE score was a significant factor in predicting
      future near-fatal DSH. In conclusion, symptoms of bulimia nervosa may have
      important clinical implications. The BITE may be a useful tool to assess future
      suicidal behavior in female self-cutting patients.

PMID- 18717159
TI  - A review of chemical-approach and ultramorphological studies on the development
      of fluoride-releasing dental adhesives comprising new pre-reacted glass ionomer
      (PRG) fillers.
AB  - This paper reviews our recent studies on fluoride-releasing adhesives and the
      related studies in this field based on information from original research papers,
      reviews, and patent literatures. A revolutionary PRG (pre-reacted glass ionomer)
      filler technology--where fillers were prepared by the acid-base reaction of a
      fluoroaluminosilicate glass with polyalkenoic acid in water, was newly developed,
      and a new category as "Giomer" was introduced into the market. On fluoride
      release capability, SIMS examination revealed in vitro fluoride ion uptake by
      dentin substrate from the PRG fillers in dental adhesive. On bonding durability,
      it was found that the improved durability of resin-dentin bonds might be achieved
      not only via the strengthened dentin due to fluoride ion uptake from the PRG-Ca
      fillers, but also due to retention of relatively insoluble 4-AETCa formed around
      remnant apatite crystallites within the hybrid layer in 4-AET-containing self
      etching adhesives. On ultramorphological study of the resin-dentin interface, TEM
      images of the PRG-Ca fillers revealed that the dehydrated hydrogel was barely
      distinguishable from normal glass fillers, if not for the concurrent presence of
      remnant, incompletely reacted glass cores. In conclusion, it was expected that
      uptake of fluoride ions with cariostatic effect from PRG-Ca fillers would endow
      dentin substrates with the benefit of secondary caries prevention, together with
      an effective and durable adhesion to dentin.

PMID- 18717160
TI  - Type I collagen grafting on titanium surfaces using low-temperature glow
      discharge.
AB  - To improve the bioactivity of titanium surfaces, glow discharge was used to
      facilitate collagen grafting on titanium disks. Titanium test specimens were pre
      treated by glow discharge fed with a mixture of argon and allylamine (AA) gases.
      Treated titanium disks were then grafted with type I collagen using
      glutaraldehyde (GA) as a crosslinking agent. The surfaces of collagen-grafted
      titanium disks were evaluated using scanning electron microscopy-energy
      dispersive spectroscopy (SEM-EDS) and X-ray photoelectron spectroscopy (XPS). MG
      63 osteoblast-like cells were cultured on the grafted titanium surfaces to
      examine the effect of collagen grafting in terms of cell morphology. Our results
      demonstrated that collagen component elements could be detected on the titanium
      surfaces. Morphology of the cells on the surfaces of collagen-grafted titanium
      disks indicated differentiation. These findings showed that type I collagen could
      be successfully grafted onto titanium surfaces using glow discharge technology,
      with enhanced biofunctionality demonstrated on osteoblastic cells.

PMID- 18717161
TI  - Effect of polymorphism of SiO2 addition on mechanical properties of Feldspathic
      porcelains.
AB  - The present study aimed to investigate the effects of SiO2 polymorphism on the
      mechanical properties of feldspathic porcelains. Seven kinds of experimental
      feldspathic porcelains were prepared using chemical reagents; three types of low
      fusing feldspathic glasses and four types of two-phase porcelains by adding 10 or
      20 mass% of fused silica (T-F) or cristobalite (T-C). Flexural strength and
      fracture toughness of these porcelains were evaluated. Flexural strengths of two
      phase porcelains did not show any significant increase when compared with those
      of single-phase glasses. On the other hand, fracture toughnesses of porcelains
      with cristobalite showed a significant increase when compared with those of
      single-phase glasses. Circumferential cracks were observed in the porcelains with
      cristobalite. These results suggested that cristobalite could strengthen fracture
      toughness of feldspathic porcelains, but not flexural strength.

PMID- 18717162
TI  - Influence of cyclic loading on fiber post and composite resin core.
AB  - From a selection of four kinds of post and core systems, including a fiber post
      and composite resin core, the purpose of this study was to determine the most
      effective system for the restoration of endodontically treated teeth with 0 mm of
      coronal tooth structure. For experimental abutment teeth, typical human maxillary
      central incisor teeth were modeled using bovine mandibular incisor teeth. By
      means of a static loading test, the four restoration systems were evaluated and
      compared in terms of failure load and failure mode. Further, by means of a cyclic
      loading test, these systems were assessed in terms of durability. For fiber post
      and composite resin core, it excelled from the standpoints of failure load and
      failure mode, and fared favorably too in durability after cyclic loading test.
      For composite resin post-and-core, it also showed excellent results for both
      failure load and failure mode in static loading test, but durability
      significantly decreased with cyclic loading. Taken together, the fiber post and
      composite resin core was found to be most effective from the standpoints of
      failure load, failure mode, and durability.

PMID- 18717163
TI  - Effect of preparation design on the fracture resistance of zirconia crown
      copings.
AB  - The aim of this in vitro study was to evaluate the effects of different
      preparation designs on the fracture resistance of single-crown zirconia
      frameworks. To this end, maxillary molar dies of CrCo alloy were fabricated with
      five different preparation designs: shoulderless, slight and pronounced deep
      chamfer, beveled and non-beveled shoulder. Ten zirconia copings with a wall
      thickness of 0.4 mm were fabricated for each type of preparation. After
      cementation by glass ionomer cement, they were loaded until fracture. There were
      significant differences in the breaking load of the experimental groups (ANOVA, p
      < 0.01). The shoulder preparation had a mean breaking load of 2286 N, the
      shoulderless preparation 2041 N, the beveled shoulder 1722 N, the pronounced deep
      chamfer 1752 N, and the slight chamfer 1624 N. Based on the results of this
      study, a shoulder preparation is highly recommended whenever possible. Moreover,
      for endodontically treated teeth that are structurally compromised or which have
      anatomically limited areas, the slight chamfer preparation is an optimal
      recommendation.

PMID- 18717164
TI  - Comparison of osteogenic potential between apatite-coated poly(lactide-co
      glycolide)/hydroxyapatite particulates and Bio-Oss.
AB  - Previously, we developed a poly(lactide-co-glycolide)/nano-hydroxyapatite
      (PLGA/HA) composite that overcame the limitations of conventional ceramic bone
      substitutes. This was achieved by introducing a bone-like apatite layer on the
      composite to further enhance its osteogenic potential. In this study, we compared
      the osteogenic potential of the apatite-coated PLGA/HA particulates to that of
      Bio-Oss, a deproteinized bovine bone material. A mixture of fibrin gel and either
      apatite-coated PLGA/HA particulates or Bio-Oss was implanted into critical-size
      rat calvarial defects. As a control, fibrin gel was implanted alone into the
      defects. At eight weeks after treatment, histological examination showed new bone
      formation around the grafting materials, and bone formation was similar between
      the two groups. In the control group, bone was not regenerated and the defects
      were filled with fibrous tissues. This study showed that a synthetic bone graft
      material, apatite-coated PLGA/HA particulates, had a comparable bone regeneration
      potential to the bovine-derived bone graft material, Bio-Oss.

PMID- 18717165
TI  - Influence of polymerization mode on degree of conversion and micropush-out bond
      strength of resin core systems using different adhesive systems.
AB  - The aim of this study was to evaluate the influence of different polymerization
      modes on degree of conversion and micropush-out bond strength of dual-polymerized
      resin core systems to dentin by using two different adhesive systems. Two resin
      core systems, Rebilda DC and Build-It FR, were used in combination with total
      etch (Adper Scotchbond Multi-Purpose) and self-etch (Clearfil SE Bond) adhesive
      systems. After treatment of dentin surfaces, resin core systems were applied into
      the cavities and subjected to different polymerization modes as follows: (1)
      chemical polymerization; (2) dual polymerization with standard mode of LED
      (Elipar FreeLight 2 LED); or (3) dual polymerization with exponential mode of
      LED. The cavities (n=10 per group) were tested in a universal testing machine.
      Degree of monomer conversion (DC%) was determined by Fourier transform infrared
      spectroscopy (n=5 cavities per group). ANOVA revealed that resin core (p =
      0.002), adhesive system (p < 0.001), and polymerization mode (p < 0.001) had
      significant effects on bond strength values. The degree of conversion for resin
      cores decreased significantly (p < 0.001) when only chemical polymerization was
      employed.

PMID- 18717167
TI  - Bond strength comparison and scanning electron microscopic evaluation of three
      orthodontic bonding systems.
AB  - This study sought to assess the efficacy of two self-etching primer systems
      (Transbond Plus and Beauty Ortho Bond) on orthodontic brackets. Therefore, shear
      bond strengths and bracket-adhesive failure modes (ARI scores) were determined
      and compared against an etch-and-rinse adhesive system (Transbond XT) under two
      experimental conditions (dry and saliva application). Shear bond strength test
      was performed at a crosshead speed of 0.5 mm/min, while enamel surfaces and
      enamel-adhesive interfaces were examined with SEM. There were no significant
      differences between Transbond XT (9.15 MPa) and Transbond Plus (9.74 MPa) under
      the dry condition, whereas that of Beauty Ortho Bond (6.47 MPa) was significantly
      lower than these two systems. Under SEM examination, both self-etching primers
      showed a milder etching effect and decreased depth of resin penetration into
      intact enamel than Transbond XT. In conclusion, results of this study showed that
      both self-etching systems seemed to offer more merits than conventional acid
      etching because of fewer irreversible changes to enamel.

PMID- 18717166
TI  - Tensile bond strength of one-step self-etch adhesives to Er:YAG laser-irradiated
      and non-irradiated enamel.
AB  - This study determined the bond strengths to Er:YAG laser-irradiated and non
      irradiated bovine enamel of three one-step self-etch adhesives (AQ Bond Plus
      (AQP), G-Bond (GB), and Clearfil Tri-S Bond (TS)) and one two-step self-etch
      adhesive (Clearfil Megabond (MB)). Eighty SiC paper-ground bovine enamel surfaces
      were used, of which half were laser-irradiated. The enamel surfaces were bonded
      to a resin composite with each adhesive, and tensile bond strengths were
      determined after 24 hours. For non-irradiated enamel groups, MB achieved greater
      bond strength to enamel than GB and TS (p < 0.05), but no significant difference
      was found between MB and AQP (p > 0.05). For laser-irradiated enamel groups, no
      significant differences were found among the four adhesives (p > 0.05).
      Additionally, for each adhesive, no significant differences were found between
      laser-irradiated and non-irradiated enamel. It was thus concluded that Er: YAG
      laser irradiation of enamel did not affect the tensile bond strength of one-step
      and two-step self-etch adhesives.

PMID- 18717168
TI  - Microtensile bond strengths of composite cores to pulpal floor dentin with resin
      coating.
AB  - The purpose of this study was to evaluate the effect of resin coating on the
      microtensile bond strength (MTBS) of indirect composite cores to pulpal floor
      dentin. Thirty extracted human molars with root canal fillings were used. After
      post space preparation, dentin surface was coated with either Clearfil SE Bond
      (SE) or SE with Clearfil Flow FX (SE+FX) for the resin-coated groups, while
      dentin was treated with ED Primer II (ED) for the non-coated group. Indirect
      composite cores were cemented with either Panavia F2.0 (PA) or Clearfil DC Core
      Automix (DC). After 24-hour storage, MTBSs were measured at a crosshead speed of
      1 mm/min. Two-way ANOVA indicated that the MTBSs of resin-coated groups were
      significantly higher than those of the non-coated groups. In particular, the
      SE+FX/DC group exhibited the highest MTBS. It was thus concluded that resin
      coating enhanced the dentin bond strength of indirect composite cores to pulpal
      floor dentin.

PMID- 18717169
TI  - Mechanical properties of dental zirconia ceramics changed with sandblasting and
      heat treatment.
AB  - Two types of tetragonal zirconia polycrystals (TZP), a ceria-stabilized TZP/Al2O3
      nanocomposite (CZA) and a conventional yttria-stabilized TZP (Y-TZP), were
      sandblasted with 70-microm alumina and 125-microm SiC powders, then partially
      annealed at 500-1200 degrees C for five minutes. Monoclinic ZrO2 content was
      determined by X-ray diffractometry and Raman spectroscopy. Biaxial flexure test
      was conducted on the specimens before and after the treatments. Monoclinic ZrO2
      content and biaxial flexure strength increased after sandblasting, but decreased
      after heat treatment. However, in both cases, the strength of CZA was higher than
      that of Y-TZP. Raman spectroscopy showed that a compressive stress field was
      introduced on the sample surface after sandblasting. It was concluded that
      sandblasting induced tetragonal-to-monoclinic phase transformation and that the
      volume expansion associated with such a phase transformation gave rise to an
      increase in compressive stress on the surface of CZA. With the occurrence of such
      a strengthening mechanism in the microstructure, it was concluded that CZA was
      more susceptible to stress-induced transformation than Y-TZP.

PMID- 18717170
TI  - Surface properties and biocompatibility of acid-etched titanium.
AB  - The purpose of this study was to evaluate the effects of acid-etched titanium on
      the biological responses of osteoblast-like MC3T3-E1 cells. Four types of
      treatments (polishing, sandblasting, concentrated H2SO4 etching, and concentrated
      H2SO4 etching with vacuum firing) were carried out on the surfaces of
      commercially pure titanium (cpTi) disks. MC3T3-E1 cells were then cultured on the
      treated cpTi surfaces. Through surface roughness measurement and SEM analysis, it
      was found that the acid-etched surfaces showed higher roughness values than the
      sandblasted ones. Scanning electron microscope analysis showed that the cells on
      the disks treated with acid-etching and acid-etching with vacuum firing spread as
      well as the sandblasted ones. There were no significant differences in cell
      proliferation and collagen production on cpTi among the four different surface
      treatments. Based on the results of this study, it was concluded that etching
      with concentrated sulfuric acid was a simple and effective way to roughen the
      surface of titanium without compromising its biocompatibility.

PMID- 18717171
TI  - Marginal and internal fit of all-ceramic crowns fabricated with two different
      CAD/CAM systems.
AB  - This study evaluated the accuracy of marginal and internal fit between the all
      ceramic crowns manufactured by a conventional double-layer computer-aided
      design/computer-aided manufacturing (CAD/CAM) system and a single-layer system.
      Ten standardized crowns were fabricated from each of these two systems:
      conventional double-layer CAD/CAM system (Procera) and a single-layer system
      (Cerec 3D). The copings and completed crowns were seated on the abutments by a
      special device that facilitated uniform loading, and the marginal discrepancies
      were measured. Internal gaps were also measured using a low-viscosity silicone
      material. Marginal discrepancies of Procera copings were significantly smaller
      than those of Procera crowns and Cerec 3D crowns (p < 0.05), but Procera crowns
      and Cerec 3D crowns did not differ significantly from each other (p > 0.05). On
      internal gaps, Cerec 3D crowns showed significantly larger internal gaps than
      Procera copings and crowns (p < 0.05). Within the limitations of this study, the
      single-layer system demonstrated acceptable marginal and internal fit.

PMID- 18717172
TI  - Effects from applying adhesive agents onto silanated porcelain surface on the
      resin bond durability.
AB  - This study examined the effects on the bond durability of resins arising from the
      application of adhesive agent on porcelain surface, silanated by a ceramic primer
      consisting of gamma-methacryloxypropyltrimethoxysilane (gamma-MPTS), by comparing
      shear bond strengths before and after thermocycling. When an adhesive agent was
      applied to a porcelain surface which had been silanated by a ceramic primer for
      10 seconds, a significant reduction in resin bonding durability was observed.
      Extending the silanating period of the ceramic primer to 60 minutes resulted in
      an increase in resin bonding durability to the porcelain surface. However, the
      effect on resin bonding durability resulting from the application of adhesive
      agent was nearly the same as that without adhesive agent application, even though
      the porcelain surface was silanated for 60 minutes. In other words, positive
      effects arising from adhesive agent application on resin bonding durability were
      not observed.

PMID- 18717173
TI  - Effect of pulse duration of Er: YAG laser on dentin ablation.
AB  - The present study examined the effects on dentin ablation efficiency arising from
      various pulse durations of Er: YAG laser at a fixed energy fluence. Ten flat
      human dentin disks were prepared and exposed to an Er: YAG laser at 1 pps for
      three seconds at pulse durations of 100-500 microsec with 150 mJ/pulse (40.0 J/cm
      x pulse). The depth and diameter of the ablated dentin were measured and the
      ablation volume was estimated. Irradiated surfaces and cross-sections were
      observed using a SEM. Depth of the removed dentin increased and the diameter of
      the spot decreased without a change in the estimated volume at increased pulse
      durations. SEM observation of the irradiated surfaces revealed that there were no
      morphological differences when the pulse duration was changed. When the specimens
      were cross-sectioned, the ablated dentin had a dome shape and there was a dark
      layer under the irradiated surface.

PMID- 18717174
TI  - A prospective study on the clinical performance of polysiloxane soft liners: one
      year results.
AB  - OBJECTIVE: The aim of the present study was to evaluate the clinical performance
      of four denture soft liners up to 12 months. MATERIALS AND METHODS: Thirty-three
      edentulous patients who experienced difficulties when using hard denture bases
      because of changes in denture-supporting tissues were accepted for the study and
      randomly received Molloplast B, GC Reline Soft, Silagum Comfort, or Mollosil Plus
      relines. Performance of the materials was evaluated using nine criteria at 3, 6,
      and 12 months: physical integrity, surface detail, adhesion, color, odor, plaque
      accumulation, resilience, hygiene, and mucosal condition. A four-point
      categorized scale (1=poor, 2=fair, 3=good, 4=excellent) was used. Unscheduled
      maintenance events and the presence of fungal colonization were also recorded.
      RESULTS: The percentage of patients available at 3, 6, and 12 months were 91%,
      91%, and 66%. Main reasons for dropouts and discontinuation were fractured
      dentures and patient dissatisfaction. At 6 months, 96% of the performance scores
      were good or excellent and the largest changes were observed for physical
      integrity, surface detail, color, and fungal colonization. Fungal colonization
      was the most commonly observed problem and was the only reason of failure at 12
      months. CONCLUSIONS: The clinical performance of all soft liners was slightly
      impaired over the 12-month observation. Except for cases showing extensive fungal
      colonization, the observed changes in clinical performance did not necessitate
      remaking of the dentures. Mollosil Plus showed a performance comparable to that
      of Molloplast B, and the other materials had slightly lower performance
      especially in terms of fungal colonization.

PMID- 18717175
TI  - Effect of zirconia surface treatments on the shear strength of zirconia/veneering
      ceramic composites.
AB  - Aim of the investigation was to assess the effect of different surface treatments
      on the bond strength of veneering ceramics to zirconia. In a shear test, the
      influences of polishing, sandblasting, and silica-coating of the zirconia surface
      on bonding were assessed with five different veneering ceramics. In addition the
      effect of liner application was examined. With one veneering ceramic, the impact
      of regeneration firing of zirconia was also evaluated. Statistical analysis was
      performed with one-way ANOVA and post hoc Scheffe's test. Failure in every case
      occurred in the veneering ceramic adjacent to the interface with a thin layer of
      ceramic remaining on the zirconia surface, indicating that bond strength was
      higher than the cohesive strength of the veneering ceramic. Shear strength ranged
      from 23.5 +/- 3.4 MPa to 33.0 +/- 6.8 MPa without explicit correlation to the
      respective surface treatment. Regeneration firing significantly decreased the
      shear strength of both polished and sandblasted surfaces. Findings of this study
      revealed that bonding between veneering ceramics and zirconia might be based on
      chemical bonds. On this note, sandblasting was not a necessary surface
      pretreatment to enhance bond strength and that regeneration firing was not
      recommended.

PMID- 18717176
TI  - Evaluation of flowable resin composite surfaces eroded by acidic and alcoholic
      drinks.
AB  - The purpose of this study was to evaluate the morphological changes of the
      surfaces of flowable resins eroded by orange juice and alcohol drinks. The tested
      products were Beautifil Flow BF02 and BF10, Clearfil Majesty LV, Filtek Supreme
      XT Flowable Restorative, Unifil LoFlo Plus and Filtek Supreme. Filler percentages
      of flowable resins were calculated after the latter were incinerated at 750
      degrees C. Specimens were shaped into a disk form with a diameter of 10 mm and a
      thickness of 1 mm. Morphological changes were evaluated for the following types
      of flowable resin surfaces: polished surface, surfaces eroded by 100% orange
      juice, wine and whisky. Filler percentages of the tested flowable resins ranged
      between 42 and 78%. Surface degradation was observed for the specimens immersed
      in acidic and alcoholic drinks, and it was thought that the lower the filler
      percentage, the greater was the surface degradation. Decomposition of the matrix
      resin and fallout of the fillers were observed in flowable resins that eroded
      with acidic and alcoholic drinks.

PMID- 18717177
TI  - Temperature rise under normal and caries-affected primary tooth dentin disks
      during polymerization of adhesives and resin-containing dental materials.
AB  - The purpose of this study was to compare the temperature rise under normal and
      caries-affected primary tooth dentin during photopolymerization of two adhesives
      and resin-containing restorative materials. Caries-affected and normal dentin
      disks were prepared from extracted primary molars with only mesial or distal
      approximal caries (4 mm in diameter, 1 mm in height). Temperature rise during
      photopolymerization of adhesive materials was measured with a J-type thermocouple
      wire that was connected to a data logger. Data were analyzed with two-way ANOVA
      and independent samples t-test. Temperature rise under caries-affected primary
      tooth dentin disks was higher than that of normal primary tooth dentin disks
      during polymerization of both adhesive systems and resin-containing dental
      materials (p < 0.05). It was found that adhesive systems induced a higher
      temperature rise during polymerization as compared to the resin-containing
      restorative materials (p < 0.05). In particular, temperature rise during
      polymerization of adhesive materials exceeded 5.5 degrees C under caries-affected
      primary tooth dentin.

PMID- 18717179
TI  - [Clinical approach and pathological cascabe of dementia].
AB  - The number of patients with dementia is explosively increasing in major
      industrialized nations and Asian countries. It is estimated about 2,430,000
      patients in the world, 4,000,000 patients in United States and more than
      2,000,000 patients in Japan. The number of patients suffered from dementia is
      predicted to be 4,000,000 patients and occupy and 11% of Japanese population in
      2040. Therapy for cure of dementia is still investigated. For this reason,
      dementia is the most important urgent and crucial concern in the national health
      and welfare. The major cause of dementia is Alzheimer disease. In this review,
      clinical symptom and natural course of Alzheimer disease, newly standardized
      criteria and neuropsychiatric butteries for Alzheimer disease are summarized.
      Possibility therapy to cure Alzheimer disease targeting Abeta oligomer and
      advances in research of biomarkers and amyloid imaging are also commented.

PMID- 18717178
TI  - Bond strengths of three different dentin adhesive systems to sclerotic dentin.
AB  - The two-fold aims of this study were: (1) to evaluate the microtensile bond
      strengths of different adhesive systems to sclerotic and sound palatal dentin;
      and (2) to observe the respective resin-dentin interfaces. Thirty extracted human
      incisor teeth were divided into two groups. Group I comprised sclerotic defects
      in the palatal zone. Group II comprised sound palatal dentin surfaces as control.
      Each group (n=15) was divided into three subgroups according to dentin adhesive
      systems: self-etch (Clearfil SE Bond), total-etch (Scotchbond Multi-Purpose
      Plus), and glass ionomer (Reactmer Bond) adhesive systems. The specimens were
      subjected to tensile forces. Obtained data were analyzed by two-way ANOVA and
      post hoc Duncan's test. Fracture sites and resin-dentin interfaces were observed
      using a light microscope and SEM. With sound dentin, Clearfil SE Bond showed a
      significantly higher bond strength than the other adhesives (p < 0.05). With
      sclerotic dentin, although there were no significant differences in bond strength
      among the adhesives groups (p > 0.05), the bond strength values of Clearfil SE
      Bond and Scotchbond Multi-Purpose Plus were significantly decreased. On resin
      dentin interface observation, different images were presented by different
      bonding systems.

PMID- 18717180
TI  - [A nationwide survey of ALS patients on trachoestomy positive pressure
      ventilation (TPPV) who developed a totally locked-in state (TLS) in Japan].
AB  - We conducted a nationwide survey of ALS patients on tracheostomy positive
      pressure ventilation (TPPV) who had developed a totally locked-in state (TLS)
      during the period from August to November 2006, in Japan. TLS occurred in 89 of
      709 (13%) ALS patients on TPPV. On the second investigation, 29 of 41 patients
      with TLS showed complete palsy of more than two voluntary motor systems out of 4
      motor systems [respiratory, pontine and medullar (bulbar), limb and external
      ocular motor systems] successively during a certain six months. The conventional
      classification of ALS based on the initial symptoms (bulbar, upper limb and lower
      limb type) was not found to be useful for predicting the onset of TLS. Seventy
      percent the patients developed TLS within 5 years after the start of TPPV. Thirty
      seven (90%) patients finally developed total ophthalmoplegia at the onset of TLS,
      while one patient eventually developed complete bulbar palsy. One of 11 ALS
      patients with TLS, whom we experienced at Tokyo Metropolitan Neurological
      Hospital, also eventually showed complete palsy of the pontine (bulbar) motor
      system (inability to pull back the jaw). Due to the fact that TLS is a state of
      complete palsy of the voluntary motor systems for communication, which may occur
      during the course of ALS in around 15% of patients, further clinical
      investigation of TLS including cognition is thus considered to be essential for
      improving the palliative care of ALS patients on TPPV.

PMID- 18717181
TI  - [A case of probable cytomegalovirus encephalitis who restored from persistant
      disturbance of consciousness].
AB  - A 50-year-old woman presented with confusion, fever and drowsiness following an
      episode of headache and dizziness. On admission, neurological examination found
      positive pyramidal tract signs, meningeal irritation, and bilateral myoclonus in
      her arms. Laboratory tests revealed liver dysfunction, positive inflammatory
      reaction, elevated serum IgM antibody against cytomegalovirus, and increased
      cerebrospinal fluid protein of 67 mg/dl. MRI of brain by diffusion weighted
      imaging showed a wide spread hyperintense lesion in white matter and limbic
      areas. We administered aciclovir, ganciclovir and steroid pulse therapy that
      showed a limited effect in the initial stage. In spite of all these therapies,
      she suffered from status epilepticus, followed by persistent disturbance of
      consciousness for about 2 months. However, her level of consciousness and motor
      deficit were gradually improved by continuous administration of ganciclovir. The
      present case indicates that prolonged disturbance of consciousness due to
      cytomegalovirus encephalitis could be restored with continuous ganciclovir
      administration.

PMID- 18717182
TI  - [Two cases of patients with Parkinson's disease developing valvular heart disease
      while taking cabergoline].
AB  - We experienced 2 patients of valvular heart disease in Parkinson's patients
      taking cabergoline. Patient 1 was a 79-year-old woman who began taking 4 mg
      cabergoline daily after being diagnosed with Parkinson's disease (PD) in June
      2003. She presented with dyspnea in November 2005. The patient had cardiomegaly,
      pulmonary congestion, and pleural effusion, and an echocardiogram showed valvular
      heart disease in the form of aortic regurgitation (AR) (grade I), tricuspid
      regurgitation (TR) (grade I), and mitral regurgitation (MR) (grade III).
      Cabergoline was thought to have caused these phenomena, so it was replaced with
      pramipexole, and after administration of diuretics and angiotensin-converting
      enzyme inhibitors (ACEIs) the patient's symptoms gradually disappeared. MR, AR
      and TR also disappeared 3 months later. Patient 2 was a 74-year-old woman who
      presented with sluggish movement in April 2001 and subsequently developed
      Parkinson's. While being administered 700 mg levodopa (Menesit) and 4 mg
      cabergoline, the patient presented with shortness of breath in April 2005. An
      echocardiogram showed valvular heart disease in the form of MR (grade I) and TR
      (grade I). Heart function improved with the administration of diuretics. However,
      heart function again worsened in November 2005, and the patient presented with
      edema of the lungs and lower limbs. An echocardiogram in January 2006 showed
      worsening MR (grade III) and TR (grade II), and the patient also had pulmonary
      hypertension. ACEIs were administered along with diuretics and cabergoline was
      replaced with pramipexole, but the patient also developed malignant syndrome and
      disseminated intravascular coagulation (DIC) and later died. Patient 2 is the
      first case in Japan of death due to heart failure caused by the side effects of
      cabergoline. Caution is usually needed when treating a Parkinson's patient for
      valvular heart disease due to a dopamine agonist, and periodic checks for heart
      murmurs and echocardiography are crucial. When signs of heart failure develop
      during treatment with an ergot preparation of dopamine agonist, it is essential
      to immediately either stop the administration of the ergot preparation or change
      to a non-ergot preparation of dopamine agonist.

PMID- 18717183
TI  - [Recurrent embolic strokes associated with persistent left superior vena cava
      draining into the left atrium].
AB  - We report a 36-year-old man who admitted due to brain infarctions of the pons and
      cerebellum. He had a history of brain infarction 4 years ago. Chest radiograph
      and enhanced CT showed an abnormal shadow in the superior mediastinum. Chest
      enhanced CT showed dilated right and persistent left superior vena cava (PLSVC),
      and venous thrombus was detected in the thorax. The PLSVC connected directly to
      the left atrium. Abdominal CT showed surface irregularity of the bilateral
      kidney, suggesting that renal infarctions had occurred. There was no risk factor
      of systemic embolism except for PLSVC thrombosis. We thought that retention of
      blood flow caused the formation of thrombus in the PLSVC, and the thrombus flowed
      into directly the systemic circulation through the left atrium and caused
      multiple embolisms.

PMID- 18717184
TI  - [A case of glioblastoma misdiagnosed initially due to positive finding of anti
      glutamate receptor antibody].
AB  - A 53-year-old man was admitted to our hospital after suffering four attacks with
      loss of consciousness and/or topographic agnosia. Three months after the first
      attack, the cerebrospinal fluid analysis showed no abnormal findings. IgG
      autoantibodies and IgM-autoantibodies against glutamate receptor epsilon2
      (GluRepsilon2) were detected in cerebrospinal fluid and serum respectively. At
      that time, we diagnosed him as having limbic encephalopathy. Brain MRI revealed a
      high intensity lesion on T2-weighted and FLAIR images in the medial regions of
      the bilateral temporal lobes and splenium. A diffusion-weighted image revealed
      high intensity lesions which were also weakly enhanced by Gd-DTPA in the deep
      white matter beside the posterior horns. The patient then developed numbness in
      the right hand. The cerebralspinal fluid analysis, four months after the onset of
      the disease, exhibited slight pleocytosis and elevated protein. IgG
      autoantibodies against GluRepsilon2 were detected in the serum. The lesions
      beside the posterior horns were ring-like enhanced more strongly. Brain biopsy
      led to a diagnosis of glioblastoma. We suggest that patients with autoantibodies
      against GluRepsilon2 should be carefully diagnosed with limbic encephalopathy
      associated with autoimmune mechanisms even if radiological findings are typical
      of the disease.

PMID- 18717186
TI  - [Pure agraphia with topographical disorientation caused by right hemisphere
      lesion].
AB  - A 69-year-old, right-handed, Japanese male patient presented with pure agraphia
      with topographical disorientation after hemorrhage in the right parietal lobe.
      Upon developing cerebral hemorrhage, he was referred to our hospital for close
      examination of agraphia. There was no paresis or clumsiness in his extremities.
      His speech was fluent and well-articulated. Neither aphasia nor reading
      impairments was found, although there was a clear writing impairment with effort
      and hesitation. His writing of both kanji and kana letters contained additional,
      absent or deformed strokes or parts. No hemianopia, prosopagnosia, constructional
      disturbances and dressing apraxia were found. He could recognize familiar
      buildings or landscapes, but often lost his way around well-known areas. MR
      images revealed subcortical lesions of precuneus, superior and inferior parietal
      lobules in the right hemisphere, around the posterior horn of the lateral
      ventricle. He revealed pure agraphia and topographical disorientation after the
      right brain haemorrhage, without dementia or personality change. These findings
      indicate that the right parietal lobe participates in the kinesthetic movements
      of writing. Some authers have been documented cases of aphasic agraphia or alexia
      with agraphia caused by right hemisphere damage in dextrals, but pure agraphia
      caused by the lesion in the right hemisphere is very rare.

PMID- 18717185
TI  - [A case of Bickerstaff brainstem encephalitis concomitant with axonal Guillain
      Barre syndrome and ballism successfully treated with intravenous immunoglobulin
      treatment].
AB  - A 39-year-old man acutely developed diplopia, vertigo, unsteady gait, and
      disturbance of consciousness following an upper respiratory infection.
      Neurological examination showed ophthalmoplegia, facial paralysis, tetraplegia
      and loss of deep tendon reflexes. Babinski reflex was positive on the left and
      there were bilateral flexor withdrawal reflexes. He also developed ballism-like
      involuntary movements in all extremities, loss of proprioception predominantly on
      the left, and severe truncal ataxia. Anti-GQ1b IgG antibody was selectively
      elevated in serum, and CSF protein was elevated to 53 mg/dl with cell count of
      12/mm3. Nerve conduction study showed decreased amplitude of compound motor
      action potentials in all extremities, and no response in facial muscles. Cranial
      MRI showed no abnormalities whereas EEG was severely abnormal with lack of
      posterior dominant rhythm and the presence of continuous diffuse theta-waves.
      This case presented clinical characteristics of three syndromes concurrently
      Fisher syndrome, Bickerstaff brainstem encephalitis, and Guillain-Barre syndrome
      that may be collectively called 'anti-GQ1b IgG antibody syndrome'. The unique
      feature of the present case was development of deep coma and ballism-like
      movements, associated with selective increase of serum anti-GQ1b IgG antibody. It
      is thus conceivable that anti-GQ1b IgG antibody might underlie the pathogenesis
      of all three conditions.

PMID- 18717187
TI  - Different role of macrophages and vascular smooth muscle cells in atherosclerotic
      lesions of Watanabe heritable hyperlipidemic (WHHL) rabbit between aorta and
      coronary artery.
AB  - The WHHL rabbit is often used to investigate the pathogenesis of atherosclerosis.
      Here we elucidate differences in the pathogenesis of atherosclerosis in coronary
      arteries (CA) and aorta (AO) by comparing dynamic changes in the distribution of
      vascular smooth muscle cells (VSMCs), macrophages, collagen and extracellular
      deposit during atherosclerosis in WHHL rabbits. Sections of CA and AO were
      obtained at the early, transitional and advanced stages of atherosclerosis and
      stained with hematoxilin-eosin, elastica van Gieson, antibodies specific to the
      above components, antibody against proliferated cell nuclear antigen (PCNA) and
      TUNEL. The relative areas of VSMCs, macrophages, collagen fibers and lipid
      deposits were calculated. In the early-stage atherosclerosis, VSMCs were
      predominant in CA lesions, while macrophages were predominant in AO lesions. PCNA
      positive VSMCs and macrophages were noted in early-stage atherosclerosis in CA
      and AO. Collagen type I, III-V fibers were present in early-stage lesions of the
      AO, while type VI increased in the deep layer during the progression of
      atherosclerosis. The proportion of apoptotic cells increased in CA and AO lesions
      with the progression in atherosclerosis. Our results showed differences in the
      distribution patterns of VSMCs and macrophages at various stages of
      atherosclerosis in CA and AO of WHHL rabbits.

PMID- 18717188
TI  - Regression analysis of maternal smoking effect on birth weight.
AB  - Risk factors for low birth weight (LBW) have been indicated in many studies, but
      in Japan few studies have examined the amount of reduction in birth weight (BW).
      The goal of this study was to examine the association between maternal smoking
      among pregnant women and subsequent reduction in BW, corrected by the effect of
      potential confounders. To assess the effect of background factors other than
      maternal smoking, we established a model to estimate the contribution of each
      explanatory variable using logarithmic multiple regression. We then used the
      adjusted BW model to evaluate the direct effect of maternal smoking. To obtain
      information on maternal characteristics, including smoking status and
      characteristics of their infants, including BW, we conducted a questionnaire
      survey. After statistical adjustment for background factors, the mean of BW among
      infants of participants who smoked during pregnancy was roundtable significantly
      lower than that of non-smoking participants, but there was no verification of a
      dose-response relationship. However, mean BWs were not significantly different
      when comparing participants who quit smoking during pregnancy to non-smoking
      participants, suggesting that stopping smoking during pregnancy is beneficial.

PMID- 18717189
TI  - Efficacy of latanoprost when stored at room temperature.
AB  - We compared the ocular hypotensive effect for 24 hours and the tolerability of
      latanoprost stored at 4 degrees C and 30 degrees C. Seventeen healthy volunteers
      were included in this crossover trial. Latanoprost 0.005% (Xalatan) was stored at
      4 degrees C or 30 degrees C for 4 weeks in the dark. The subjects enrolled to the
      study were randomly assigned to receive either latanoprost stored at 4 degrees C
      or that stored at 30 degrees C. The eye drop was applied to the right eye of each
      subject for 3 days. The left eye served as a control without administration. Slit
      lamp biomicroscopy and circadian intra ocular pressure (IOP) curve was performed
      at Day 3, every 3 hours from 6 pm. This procedure was repeated 7 days after
      changing the drug from 4 degrees C to 30 degrees C or vice versa, and application
      to the left eye for 3 days. Eyes treated with latanoprost, stored both at 4
      degrees C and 30 degrees C, achieved statistically significantly lower mean IOPs
      than untreated eyes at all time points, except at 21 hours treated by the drug
      stored at 30 degrees C. We subtracted the IOP of eyes receiving latanoprost from
      the IOP of untreated eyes for each time point to evaluate the efficacy of the eye
      drops (delta IOP). There were no statistically significant differences between
      the delta IOPs with the drug stored at 4 degrees C and 30 degrees C. During the
      study, no subject developed a serious adverse event. These results suggest that
      latanoprost stored at 30 degrees C for 4 weeks after opening the bottle remains
      as effective and safe as latanoprost stored under cold conditions.

PMID- 18717190
TI  - Role of vascular endothelial growth factor-C and -D mRNA in breast cancer.
AB  - Vascular endothelial growth factor (VEGF)-C and VEGF-D belong to the VEGF family,
      and are thought to be involved in lymphangiogenesis and angiogenesis. At present,
      this is the only known system that can induce lymphatic vessel growth in the
      body. However, the roles of VEGF-C and VEGF-D in breast cancer tissue have not
      been clarified. In the present study, we measured the mRNA expression of VEGF-C
      and VEGF-D in the breast cancer tissue of 109 patients by real-time polymerase
      chain reaction (RT-PCR). Between non-infiltrating breast cancer (n=6) and
      infiltrating breast cancer (n=103), there were no significant differences in the
      mRNA expression of VEGF-C and VEGF-D. In infiltrating cancer, the expression of
      HER2 exhibited a positive correlation to VEGF-C and VEGF-D mRNA expression
      (p=0.027, p=0.048). However, mRNA expression ofVEGF-C and VEGF-D did not exhibit
      any significant correlation to lymphatic vessel invasion or lymph node
      metastasis. Among patients without lymph node metastasis, the mRNA expression of
      VEGF-C and VEGF-D for patients with lymphatic vessel invasion was significantly
      higher than that for patients without lymphatic vessel invasion (p=0.001,
      p=0.050). The results suggest that, in breast cancer, VEGF-C and VEGF-D are
      involved in lymphatic vessel invasion prior to lymph node metastasis, and their
      expression decreases after lymph node metastasis occurs.

PMID- 18717191
TI  - [Epidemiology and etiology of dural arteriovenous fistula].
AB  - Dural arteriovenous fistula (DAVF) is generally recognized as an acquired lesion;
      however, its epidemiology, etiology, and natural history are yet to be completely
      elucidated. Recently, an epidemiological survey of the detected DAVF cases in
      Japan between 1998 and 2002 was conducted. The detection rate of DAVF per 100,000
      adults per year is 0.29 for DAVF. Furthermore, unlike Europe and North America
      where cases of transverse-sigmoid sinus DAVF are predominantly detected, in
      Japan, a higher number of cases of cavernous sinus lesions are detected,
      indicating racial difference in the presentation of DAVF. Our study indicates
      that dural sinus thrombosis, which is generally considered as a causative factor
      of DAVF, is less likely to precede the detection of DAVF. A possible mechanism
      underlying the formation of DAVF is as follows: subtle changes, including minor
      trauma, cause the formation of an abnormal arteriovenous shunt in the dura and
      promote progressive steno-occlusive change in its venous drainage.

PMID- 18717192
TI  - [Classification and diagnosis of intracranial dural arteriovenous fistulas].
AB  - Intracranial dural arteriovenous fistulas (DAVFs) are abnormal connections
      between the dural arteries and dural veins in the cranial dura mater. These
      fistulas involve the cavernous sinus, transverse-sigmoid sinus, superior sagittal
      sinus, inferior/superior petrosal sinus, sphenoparietal sinus, anterior cranial
      base, tentorium, craniocervical junction, and anterior condylar confluence.
      Presently, there are several classifications according to the venous restrictive
      condition. These classifications are useful in both determining the hemodynamic
      status of the patient and in formulating treatment strategies. The clinical signs
      and symptoms of these fistulas essentially result from hypertensive venopathy
      with or without venous hemorrhages. Patients with aggressive course are
      characterized by retrograde leptomeningeal venous drainage and veneous
      restrictive lesions. Besides location specific symptoms, intracranial venous
      hypertension is a key mechanism mimicking benign intracranial hypertension.
      Angiographic evaluation of the impairment in cerebral venous drainage is
      important as well as evaluating the angioanatomical features of the feeding and
      draining vessels and of the fistula sites. The characteristic findings of modern
      diagnostic tools such as CT scan, MRI, and conventional angiography are also
      described in this study.

PMID- 18717193
TI  - [Surgical treatment of intrarcranial dural arteriovenous fistulas].
AB  - Surgical treatment is indicated in patients who present clinical symptoms for
      intracranial dural arteriovenous fistula and retrograde cortical venous filling
      on cerebral angiography. Further, surgery is indicated in those patients that
      cannot be cured by endovascular procedures. For dural arteriovenous fistulas in
      the anterior fossa, tentorium, craniovertebral junction or convex, surgery was
      considered as the first option. Morphologically, non-sinus dural arteriovenous
      fistulas and dural arteriovenous fistulas with isolated sinus should be treated
      with surgery. The surgical procedure for intracranial dural arteriovenous
      fistulas basically consisted of the coagulation and disconnection of the
      retrograde-flow cortical veins at the point of entry into the dural sinus, and
      the coagulation of the affected dura and dural sinus. The remaining affected
      dural sinus could be removed if the patient could tolerate the surgery.
      Preoperative transarterial embolization of the feeding artery is effective in
      reducing the amount of blood loss intraoperatively. During surgery, microvascular
      Doppler sonography is useful for confirming the retrograde-flow cortical veins,
      and stereotactic localization system and duplicated ultrasound sonography are
      also useful in detecting the shunting point of the dural arteriovenous fistula
      and the range of the affected dura and dural sinus. The surgical procedure for
      intracranial dural arteriovenous fistulas is a radical and invasive treatment.
      However, surgery is a reliable treatment because it can cure the intracranial
      dural arteriovenous fistula and correct the intracranial hemodynamics immediately
      after surgery due to the extirpation of the dural arteriovenous shunt and
      retrograde-flow cortical veins.

PMID- 18717194
TI  - [Endovascular treatment for dural arteriovenous fistula].
AB  - Intracranial dural arteriovenous fistulas (DAVFs) are acquired abnormal epidural
      arteriovenous shunts, particularly at the sinus wall. Most of the DAVFs are
      associated with progressive sinus occlusion. They are located in the cavernous
      sinus, lateral (transverse-sigmoid) sinus, superior-sagittal sinus, anterior
      condylar confluence, tentorial sinus, craniocervical junction, and anterior skull
      base (ethmoidal sinus). The treatment strategy differs based on the etiology and
      drainage pattern of DAVFs. The most effective treatment for DAVFs at the sinus
      wall is transvenous embolization (TVE) with coils. The target coil packing is
      effective if the sinus point is identified. Certain cases that are difficult to
      approach transvenously are treated with transarterial embolization (TAE) by using
      liquid materials like such glue. In particular cases with sinus occlusive lesion
      sinus reconstruction with sinoplasty is effective. The cases with failed or
      impossible endovascular approach should be treated with surgical interruption of
      shunts or by radiosurgery. The most frequent complication of TAE is brain and
      nerve ischemia due to the overembolization or migration, and that in TVE is the
      bleeding due to obstruction of the drainage route and nerve compression due to
      overpacking of coils.

PMID- 18717195
TI  - [Radiosurgery for intracranial dural arteriovenous fistulas--indications for
      limitations for gamma knife treatment].
AB  - We summarize the results of gamma knife treatment for dural arterivenous fistula
      (DAVF), are report our study. Since the early 1990s, DAVFs have been treated in
      the same manner as arteriovenous malformations (AVMs), i.e., by radiosurgery,
      performed with or without embolization. DAVFs in the cavernous sinus, transverse
      sigmoid sinus, and cerebellar tent were treated with a marginal dose of 18 to 20
      Gy. The current obliteration rates of DAVF reported in literature are not low
      when compared with those of AVM. Excellent DAVF obliteration rates were observed
      in our study, which were similar to those reported in the literature. In fact,
      complete response (CR) was observed in 9 cases, partial response (PR) in 9 cases,
      and partical obliteration in 6 cases during the mean follow-up of 27 months.
      Moreover, considerable neurological improvements were noted, which apparently
      began at an early stage post radiosurgery. Bleeding was observed 2 cases
      associated with cortical reflux during the follow-up. In conclusion, radiosurgery
      for DAVF is very useful for both the obliteration of the fistula and for the
      improvement of clinical signs. However, prior to performing radiosurgery, the
      lesions with cortical reflux should be interrupted by initially treated with
      surgery or embolization.

PMID- 18717196
TI  - [Parkin and mitochondria].
AB  - Parkinson disease (PD) is the most common neurodegenerative disease, and the
      majority of PD cases involve the sporadic from of PD. Although the etiology of
      the sporadic form is unknown, mitochondrial dysfunction and oxidative stress are
      considered to play a prominent role in its pathogenesis. The discovery of the
      genes that are linked to the rare familial form of PD has provided crucial
      insights into the molecular mechanisms involved in the pathogenesis of PD. Recent
      findings implicate mitochondrial dysfunction associated with oxidative damage
      (mitochondrial pathway) and abnormal protein accumulation (ubiquitin/ proteosome
      pathway) as the key molecular mechanisms compromising dopaminergic neurons in
      familial PD. Mutations in Parkin, PTEN-induced kinase 1 (PINK1) and DJ-1 are
      found in autosomal recessive forms of PD. Recent studies on these genes suggest
      the central importance of mitochondrial dysfunction and oxidative stress in PD.
      The above mentioned 3 proteins may be biologically related to each other and may
      protect the mitochondria against oxidative stress and other harmful stimulations.
      In particular, parkin appears to be the most important factor that improves the
      mitochondrial dysfunction. In this review we focus on the mitochondria and parkin
      function. We also provide an overview of the most relevant findings in recent
      years.

PMID- 18717197
TI  - [Novel vaccine therapy for Alzheimer's disease--recent progress and our
      approach].
AB  - Alzheimer's disease (AD) is the most common cause of dementia with very few drugs
      available for its treatment. In 1999, Schenk et al reported that Abeta 1-42
      peptide vaccination in AD model mice causes the reduction in Abeta deposits.
      Thereafter, a vaccine therapy was developed for the curative treatment of AD.
      Clinical trials of active vaccination for AD patients were halted due to the
      development of meningoencephalitis in some patients; however, vaccine therapy is
      thought to be effective based on the clinical and pathological findings of the
      vaccinated patients. Based on this information, active and passive vaccines have
      been developed, some of which are now urdergoing clinical trials in Europe and
      USA. However, there are still some problems for general application of such drugs
      for AD patients. Recently, we developed nonviral DNA vaccines and used them to
      obtain a substantial Abeta reduction in AD model mice without any side effects.
      In this article, we will review conventional vaccine therapies and introduce our
      non-viral DNA vaccine therapy. Finally, we will present data regarding the
      mechanisms of Abeta reduction after DNA vaccination. DNA vaccination for AD may
      open up new avenues in vaccine therapy for the treatment of AD.

PMID- 18717198
TI  - [Awake surgery plays a role in neurosurgery and neuroscience].
AB  - Awake surgery has been reported to play a role in the safe removal of brain
      tumors and detection of the functional localization of the cortex or neuronal
      tracts. In our hospital, from November 2004 to May 2007, we performed awake
      surgery with continuous tasks in 33 cases of brain tumors within or near the
      primary motor area (M1). The relationship between the extent of resection and
      postoperative motor function in awake surgery cases was compared with that in
      cases of surgery under general anesthesia, which were performed prior to November
      2004. In 32 of 33 cases of awake surgery, the final postoperative motor function
      was either preserved or improved relative to the preoperative levels; however, in
      9 of 14 patients who underwent surgery under general anesthesia, deterioration in
      motor function was noted after surgery. Gross total removal (GTR) was achieved in
      20 of 33 cases of awake surgery and in 8 of 14 cases of surgery under general
      anesthesia, indicating that the extent of resection was similar between awake
      surgery and surgery under general anesthesia. In most cases of awake surgery,
      neurological deterioration occurred during internal decompression of the tumors
      or compression of the normal brain, while surgical manipulation of the tumor
      margin did not induce neurological deterioration in most cases of surgery under
      general anesthesia. Moreover, various new findings regarding the function of the
      cortex or neuronal tract have been reported in awake surgery. We discussed the
      advantages and future directions of awake surgery. In conclusion, awake surgery
      plays an important role in neurosurgery and neuroscience.

PMID- 18717199
TI  - [Germinoma presenting with personality and socio-behavioral abnormalities may
      challenge differential diagnoses].
AB  - We described the major diagnostic difficulties encountered in the case of a 25
      year-old man with the pathological diagnosis of a germinoma. The patient
      initially developed an eating disorder at the end of 2003 and a character change
      ensued since the beginning of 2004. On admission in August 2004, his cardinal
      symptoms and signs included marked apathy, depersonalization, generalized muscle
      wasting, and decreased tendon reflexes. Brain T2-weighted (T2-WI) MR and FLAIR
      images showed high signal intensities in the suprasellar region and at the genu
      of the corpus callosum that extended along the sub-pia mater of the right
      anterior horn. These lesions showed mild enhancement on gadolinium-enhanced T1
      WI. CSF examination revealed a mildly elevated level of protein and increased
      cell counts but did not show any malignant cells on repeated spinal tap. The
      patient's status remained practically unchanged till December 2004 when he
      developed diabetes insipidus. Soon afterward, the patient collapsed into akinetic
      mutism and developed corresponding new lesions at the tegmentum of the midbrain.
      These new lesions disappeared spontaneously and akinetic mutism regressed without
      any specific therapy. We tentatively diagnosed of neurosarcoidosis based on a
      characteristic progressive-regressive clinical course, CSF data, and radiological
      findings. Clinical symptoms and the enhanced masses on MRI were highly responsive
      to steroid therapy after which the patient was able to return home. However,
      disturbances in consciousness and tenacious vomiting recurred in September. Brain
      MRI revealed a markedly re-enlarged and easily enhanced mass at the right
      anterior horn, which extended into the cerebral aqueduct and resulted in
      obstructive hydrocephalus. On surgery, histopathological investigation revealed
      germinoma. This case highlights the need for careful discrimination between a
      slow growing germinoma and chronic granulomatous diseases of the brain such as
      neurosarcoidosis. Early histological investigation may be warranted in patients
      who present difficulties during differential diagnoses.

PMID- 18717200
TI  - [Case with multiple brain infarcts due to calcified emboli from a calcified
      atheroma of the innominate artery].
AB  - A 75-year-old-woman was admitted to our hospital because of acute brain
      infarction with symptoms of vertigo, conjugate deviation of the eyes, speech
      disturbances, left hemiparesis, and right limb ataxia. On admission, diffusion
      weighted MR imaging revealed a high-intensity area in the right internal carotid
      artery (ICA) and vertebrobasilar (VB) territories. MRA showed normal intracranial
      arteries. Ultrasonography with a sector probe (2MHz) showed a mobile mass with an
      acoustic echo in the innominate artery. Contrast-enhanced computed tomography
      showed a calcified mass in the innominate artery. Despite full-dose
      antithrombotic therapy, recurrent attacks could not be prevented. Replacement of
      the innominate artery was performed by cardiac surgeons, and a ruptured calcified
      plaque was found in the innominate artery. Subsequent, computed tomography of the
      brain showed calcified emboli in the right ICA and VB territories. Arterial
      ultrasonography appears to be very useful in evaluating the innominate artery. On
      finding calcified emboli, an embolic source should be searched for in the aorta,
      heart valves, and the innominate artery. When infarcts with calcified emboli are
      found only in the right ICA and VB territories, the innominate artery should be
      explored by ultrasonography for the presence of a calcified atheroma.

PMID- 18717201
TI  - [Cerebral hemodynamic changes in eclampsia--case report].
AB  - Eclampsia is a rare condition that is peculiar to pregnant and puerperal women,
      and its pathophysiology still remains unclear. We conducted a 90-day radiological
      follow-up of a 29-year-old primigravida who developed eclampsia at 41 weeks of
      gestation. On admission, magnetic resonance imaging (MRI) showed vasogenic edema
      predominantly in the parietal and occipital lobes; however with in 2 weeks, these
      lesions had disappeared. Although single-photon emission CT (SPECT) scanning
      showed hyperperfusion on day 4, hypoperfusion was shown to be in the right
      occipital lobe on days 11 and 90. These findings reveal the various changes in
      cerebral vasculature during the acute phase of eclampsia.

PMID- 18717202
TI  - [Mild headache as a presenting symptom of transverse sinus thrombosis due to oral
      contraceptives].

PMID- 18717203
TI  - [Absence of right common carotid artery shown by three-dimensional CT
      angiography].

PMID- 18717204
TI  - [Case of recurrent episode of fever and headache in 59-year-old during 10 years].

PMID- 18717205
TI  - Obesity in America.
AB  - Recent data indicate that Americans are gaining weight at an alarming rate. In
      fact, data from the CDC indicate that the U.S. obesity average was 12% in 1990
      and had grown to 23% by 2005. In recent years, this problem appears to be more
      prominent in some southern states than in other states. The purpose of this study
      was to determine what factors were associated with increased levels of obesity.
      Do demographic, educational, healthcare, or economic factors correlate with this
      trend? Using state level data in a fixed effects regression model we examined
      obesity rates for the period 1990-2003. We also used cross tabulation tables to
      compare obesity rates to several independent variables. Our analysis revealed
      that obesity was related to several health, demographic, and economic factors. As
      a result, we argue that policy makers as well as health officials should take a
      comprehensive look at obesity as well as other social ills, health care
      conditions, and related issues prior to creating a plan to improve health in this
      country.

PMID- 18717206
TI  - Being overweight and obese: Black children ages 2-5 years.
AB  - Obesity in children is a significant public health concern. The prevalence of
      obesity in Black preschoolers (ages 2-5 years) is slightly higher than in whites.
      However, by age 6, Black children experience higher obesity prevalence. The
      consequences to health throughout childhood and into adulthood have both medical
      and economic cost to individuals and society. Factors associated with obesity in
      preschool children are lifestyle behaviors such as diet, level of activity,
      culture, environment, and parental perceptions. Programs should target young
      Black children and their families to reduce the incidence of obesity and
      promoting healthy behaviors could aid in eliminating health disparities and
      improving quality of life. Nurses need to provide comprehensive culturally
      appropriate strategies at community and individual/family levels to prevent
      overweight and obesity in children.

PMID- 18717207
TI  - Black men are dying from prostate cancer.
AB  - Prostate cancer is the most frequently diagnosed cancer in the United States,
      accounting for 33% of all cancer cases among men (American Cancer Society, 2004).
      In the United States the number of new cases of prostate cancer was estimated at
      230,110 and 29,900 will die (American Cancer Society, 2004). It is anticipated
      that these numbers will continue to grow despite effective treatment regiments.
      Black men (African-American) are 2.5 times more likely to die of prostate cancer
      than White men (Peters, 2005). Recent studies suggest genetics, diet, knowledge,
      and socioeconomic status as contributory factors, however, there appears to be
      more to it.

PMID- 18717208
TI  - A faith-based screening/education program for diabetes, CVD, and stroke in rural
      African Americans.
AB  - The purpose of this study was to examine the effectiveness of a faith-based
      health screening/education program to ultimately reduce risk factors for diabetes
      (DM), cardiovascular disease (CVD), and stroke (CVA) in a southern, rural,
      African-American population. Over 120 parishioners from four rural African
      American churches attended health education/screening programs offered as a part
      of their Bible Study. The majority of participants were female, married, with a
      mean age of 45 years. The program included education about prevention of
      cardiovascular disease (CVD), diabetes (DM), and stroke (CVA) followed by health
      screening, individual counseling, and healthy snacks. Pre/post test surveys for
      health knowledge were given. While the pre/post health knowledge scores showed
      some improvement, they were not statistically significant indicating the need for
      more than one program. Participants under age 30 and over age 60 years had the
      least knowledge on the pretest about these illnesses compared to the middle-age
      group. Almost 50% were found to have high blood pressure, and 14% had high blood
      sugar levels of which they were unaware. Participant and pastor feedback was
      positive and supported the feasibility of ongoing faith-based screening/
      education programs as one way to meet the health needs of a rural African
      American population.

PMID- 18717209
TI  - A school of nursing's experience with providing health care for Hurricane Katrina
      evacuees.
AB  - This article describes how Southern University School of Nursing (SUSON)
      participated in meeting the immediate health care needs of evacuees from New
      Orleans and environs that were victims of Hurricane Katrina. It describes how
      SUSON's advanced practice nurses use a mobile health unit (the Jag Mobile) to
      continue to serve evacuees that now live in Renaissance Village, a transitional
      housing trailer park. Ideas are presented that can help schools of nursing create
      a disaster response plan.

PMID- 18717210
TI  - Pilot study of the breast cancer experiences of African American women with a
      family history of breast cancer: implications for nursing practice.
AB  - Experts in the area of breast cancer detection and control recommend that women
      at increased risk discuss their risk status and risk management with their health
      care providers. In spite of the excessive breast cancer burden borne by African
      American women, little attention has been given to studying breast cancer risk
      communication and/or breast cancer risk management in this at-risk population
      group. This report summarizes the outcomes of a study undertaken to explore the
      degree to which breast cancer, breast cancer risk, and breast cancer risk
      management were discussed by African American women and their health care
      providers Targeted for inclusion in the study were African American women who had
      a first degree relative or multiple second degree relatives that had been
      diagnosed with pre-menopausal breast cancer. Of particular interest was the
      extent to which African American women with a family history of breast cancer
      perceived themselves to be at risk for developing breast cancer and the extent to
      which they discussed their family history, their breast cancer risk, and, breast
      cancer risk management with their providers.

PMID- 18717211
TI  - Self-reported cerebrovascular and heart diseases and cardiovascular risk factors
      in Portugal: the AMALIA study.
AB  - INTRODUCTION: There is a high prevalence of cardiovascular diseases and
      associated risk factors in the European population. In order to decrease their
      incidence, it is necessary to adopt healthy lifestyles and to apply appropriate
      therapeutic measures. There is therefore a need to inform, to motivate, and to
      evaluate attitudes and the effectiveness of the measures put into practice.
      OBJECTIVES: The study's main objective is to determine the prevalence of the main
      clinical manifestations of ischemic heart and cerebrovascular diseases, as well
      as cardiovascular risk factors, according to how they are perceived, and to
      evaluate consumption of health resources (such as hospitalization and
      medication). Secondary objectives are to characterize work absenteeism and the
      quality of life of those surveyed. STUDY DESIGN: Cross-sectional study, using a
      structured questionnaire in a direct interview. POPULATION: 38,000 individuals of
      both genders, aged 40 years or more. STUDY LOCATION: Randomly selected
      municipalities in seven Portuguese regions. MEASUREMENTS: The questionnaire
      covers sociodemographic variables, cardiovascular risk factors and diseases, use
      of medication and health care services (hospitalizations, medical appointments
      and diagnostic exams) for the treatment and follow-up of these pathologies, and
      also quality of life. QUALITY CONTROL: Morbidity data were validated through a
      pilot study involving 500 individuals from Lisbon, Porto and Leiria. These
      individuals were requested to fill in the questionnaire, and their blood
      pressure, total cholesterol level, weight, height, and hip and waist
      circumference are assessed. CONCLUSIONS: Despite its limitations, which include
      the evaluation of diseases based on self-reporting, the methodology adopted is
      justified by the advantage of ease of application, notably the need for fewer
      resources. A health examination survey-type study of this size would be difficult
      to implement. The evaluation of patients' perception regarding risk factors,
      cardiovascular diseases and quality of life may help to define the needs and
      priorities for cardiovascular disease prevention and treatment, which are
      essential in order to reduce their incidence.

PMID- 18717212
TI  - On epidemiology: what will the AMALIA study bring to Portuguese cardiologists?

PMID- 18717213
TI  - Electrocardiographic presentation of massive and submassive pulmonary embolism.
AB  - INTRODUCTION: Acute pulmonary embolism (PE) is a common clinical entity in the
      emergency department, and remains a diagnostic challenge for physicians. The role
      of the 12-lead electrocardiogram (ECG) in its diagnosis and assessment of
      severity and prognosis is not as well defined as for acute coronary syndromes. We
      report four cases of massive and submassive PE with differing ECG findings
      admitted to an acute cardiac care unit. We review the role of different ECG
      abnormalities and also discuss the relevance of transthoracic echocardiographic
      data in the diagnosis and serial evaluation of patients with PE. Treatment
      options for PE with hemodynamic compromise and right ventricular dysfunction are
      also discussed. RESULTS: The ECG is abnormal in over two-thirds of patients with
      PE. Its main utility is in excluding other conditions, such as acute coronary
      syndromes. DISCUSSION: Numerous ECG abnormalities have been reported in patients
      with PE. These often change over time, with worsening or resolution of the
      embolic event. Although it is the most frequent ECG abnormality, sinus
      tachycardia lacks specificity. However, ECG findings are more specific in
      patients with severe PE (such as the classic S1Q3T3 pattern). In the case of
      massive and submassive PE, anterior and inferior T-wave inversion is the most
      frequent associated ECG finding. Serial ECG evaluation should be performed in
      such patients as changes and resolution of abnormalities may have prognostic
      implications. Transthoracic echocardiography is extremely useful in the initial
      and serial evaluation of patients with PE because of its accessibility and the
      data it provides on diagnosis, severity and resolution. Submassive PE is defined
      by echocardiographic data and could benefit from the same therapeutic options as
      for massive PE. The use of specific therapeutic strategies such as anticoagulant
      and thrombolytic therapy in both massive and submassive PE has to be carefully
      weighed. The bleeding risk and associated comorbidities of patients admitted with
      PE should always be considered. CONCLUSION: ECG findings have low sensitivity and
      specificity in the diagnosis of PE. It should be routinely used in serial
      evaluations, particularly when hemodynamic compromise is present, and should be
      included in the range of diagnostic strategies available.

PMID- 18717214
TI  - Two anomalous cardiovascular responses to active standing in essential
      hypertension.
AB  - INTRODUCTION: In a previous work we studied, non-invasively, autonomic nervous
      system control of circulation in healthy subjects, observing the hemodynamic
      reaction to active standing. We now propose to extend this analysis to essential
      hypertension (EH), investigating possible autonomic dysfunction. METHODS: The
      cardiovascular response to postural change from the supine position to active
      standing of 48 EH patients, of both sexes, with and without medication, was
      compared with that obtained for healthy subjects. We evaluated arterial systolic
      (SBP) and diastolic (DBP) blood pressure, stroke volume (SV), inotropic index
      (INOI), total vascular resistance (TVR), cardiac work (W), stroke work (SW),
      arterial compliance (AC) and heart rate (HR), using the entirely non-invasive
      BoMed NCCOM3 thoracic electrical bioimpedance monitor and sphygmomanometry.
      RESULTS: We found two patient groups characterized by different linear
      relationships between values of cardiovascular variables in active standing and
      in supine positions. Except for HR, in both groups these regression lines
      differed from normal. Compared to the supine position, in active standing, one
      group (EH-I) presented increased TVR, diminished SV, INOI, W, SW, and AC, and
      normal HR; the other group (EH-II) presented diminished TVR and HR and increased
      SV, INOI, W, SW and AC. The two patient groups could be separated on the basis of
      their age, but not on the basis of their systolic, diastolic and mean arterial
      blood pressures, gender or medication. The younger patient group (EH-I) included
      28 subjects aged 24 to 69 years (50+/-10), of whom 11 were unmedicated, and the
      older patient group (EH-II) included 20 subjects aged 35 to 75 years (62+/-11),
      of whom 7 were unmedicated. DISCUSSION: Our results show a depressed response in
      postural change for older patients, which in the autonomic control of circulation
      expresses carotid baroreflex impairment, and conversely an enhanced response for
      younger patients, which can be caused by a maladjustment of the influence of
      cardiopulmonary mechanoreflexes in the alance with arterial baroreflexes.
      CONCLUSIONS: This work suggests the existence of two different levels of
      dysautonomia in EH, according to age. The deterministic changes in cardiovascular
      variables after postural change show that, regarding autonomic nervous system
      control to maintain homeostasis, certain circulatory statuses are favored.

PMID- 18717215
TI  - Hypertrophic cardiomyopathy--state of the art in 2007.
AB  - Hypertrophic cardiomyopathy (HCM) is a primary disease of the sarcomere, with
      considerable genetic heterogeneity and variability in phenotypic expression,
      whose main complication is sudden cardiac death (SCD). Genetic aspects of HCM,
      its molecular pathophysiology and genotype-phenotype relationships are the
      subject of this review, which is aimed at better understanding of practical
      management in this patient population. As HCM is a genetic disease whose initial
      manifestation can be sudden death, it is essential to establish the diagnosis at
      an early stage, to proceed with risk stratification and implementation of SCD
      prevention strategies, and to promote genetic counseling of patients and
      screening of their families. Detection of pathological mutations through
      progressive sequencing of the genes most commonly involved is the most efficient
      way to diagnose HCM, even in the absence of clinical evidence of the disease.
      Identification of individuals at high risk of SCD is a major challenge in the
      management of this population, since SCD can be prevented by use of an
      implantable cardioverter-defibrillator. The selection of patients for
      prophylactic implantation of these devices, particularly those who have only one
      major risk factor, is currently the subject of controversy.

PMID- 18717216
TI  - [Guidelines for cardiac pacing and cardiac resynchronization therapy].

PMID- 18717217
TI  - National Registry on Cardiac Electrophysiology--2006.
AB  - Clinical electrophysiology is one of the areas of cardiology that has seen most
      growth in Portugal, particularly in interventional cardiology, which includes
      ablation of arrhythmias and prevention of sudden cardiac death. The annual
      publication of a national registry enables us to assess qualitative and
      quantitative progress, compare our results with international data, assess the
      centers' training capabilities and inform health authorities of the activities
      and needs of the sector. The authors analyze the number and type of procedures
      performed during 2006 based on a survey sent to 19 national centers (15 public
      and 4 private) that performed diagnostic and interventional electrophysiology (15
      centers) and/or implanted cardioverter-defibrillators (ICDs) (19 centers) in that
      year. The number of electrophysiology centers remained unchanged from 2005, but
      four new centers began implanting ICDs in 2006. In the year under review, 1805
      electrophysiological studies were performed, 75.3% of which were followed by
      ablation therapy, a total of 1360 ablation procedures (a 22.3% increase over the
      previous year). Accessory pathways were the main indication for ablation (32%),
      followed by atrial flutter (25%), atrioventricular nodal reentrant tachycardia
      (23%), atrial fibrillation (10%), ventricular tachycardia (5%), atrial
      tachycardia (3%) and atrioventricular junction ablation (2%). In 2006, a total of
      738 ICD devices were implanted, of which 64 were battery replacements and 674
      were first implantations, with the following distribution: 346 single chamber
      (51.3%), 98 dual chamber (14.5%) and 230 integrated in ventricular
      resynchronization systems (34.1%). These figures reflect a lower growth rate than
      that of 2005, even though in 2006 first implantations rose from 54.7 to 67.4
      devices per million population. The ICD implantation rate in Portugal is still
      far below the European average, which means there is a continuing need to raise
      awareness of this therapeutic option among the Portuguese medical community. With
      regard to the training capabilities currently available in Portugal, only 5
      centers (all public) had a sufficient level of activity to fulfill the
      requirements stipulated for the subspecialty of cardiac electrophysiology. As for
      implantation of ICDs, 12 centers implanted more than 10 units, the minimum annual
      curricular limit for this subspecialty.

PMID- 18717218
TI  - Viral myocarditis--new advances.
AB  - The role of viruses in cardiovascular disease has been increasingly recognized in
      recent years. They are now thought to be the main agent in acute myocarditis and
      inflammatory cardiomyopathy in the western world. We describe new perspectives on
      the part viral agents play in heart disease, from molecular mechanisms to
      recently available diagnostic and therapeutic options. We present a case of post
      viral dilated cardiomyopathy in a 29-year-old woman in order to illustrate the
      severe damage that a viral infection can cause and the different therapeutic
      options that may be available in the near future.

PMID- 18717219
TI  - A rare histiocytosis with severe cardiac involvement: Erdheim-Chester disease.
AB  - The term histiocytosis covers various disorders that lead to primary
      proliferation, infiltration and accumulation of cells of the mononuclear
      phagocytic system within the affected tissues. Its pathophysiology is still
      unclear and the clinical course variable, which explains the lack of specific
      treatment and the need for a high level of suspicion to arrive at the diagnosis.
      The authors present the case of a patient with a complex cardiological clinical
      history, recently referred for surgical treatment of severe mitral insufficiency.
      Severe thickening of both atrial walls made it impossible to proceed with the
      intervention. After a complex etiological evaluation, a diagnosis of Erdheim
      Chester disease was made. This is a rare, non-Langerhans cell histiocytosis and,
      to our knowledge, this represents the first case reported in Portugal. The
      authors also review the literature, particularly of the few cases with cardiac
      involvement.

PMID- 18717220
TI  - Intra-aortic thrombi and mesenteric ischemia: a presentation of polyarteritis
      nodosa.

PMID- 18717221
TI  - [Discussing what is the meaning of prevention].

PMID- 18717222
TI  - [Popularizations in epidemiology].

PMID- 18717223
TI  - [Doubts about estimates of the number of workers at risk of lung cancer].

PMID- 18717224
TI  - [Some thoughts about the ethics of scientific publishing and Epidemiologia &
      Prevenzione].

PMID- 18717225
TI  - [Carcinogenicity of hexavalent chromium in animals and humans when adsorbed from
      the gastrointestinal tract].

PMID- 18717226
TI  - [The health and safety of workers. A time for emotions and a time to legislate].

PMID- 18717227
TI  - [A criticism to the WHO workshop on waste management and health (Rome, March
      2007)].

PMID- 18717228
TI  - [Financing of the tobacco industry and lung cancer screening].

PMID- 18717229
TI  - [Has the Kaposi sarcoma epidemic declined in Italy?].

PMID- 18717230
TI  - [Incidence of tuberculosis in Piedmont Region in the period 2001-2003].
AB  - OBJECTIVES: tuberculosis is a global heath priority and the surveillance systems
      are essential tools to control the spread of the disease. The objectives are to
      estimate: the incidence tuberculosis in Piedmont for the period 2001-03, using
      multiple sources of information; the sensitivity of the regional system for the
      surveillance of tuberculosis; the impact ofimmigration from areas with high
      prevalence of tuberculosis. DESIGN: deterministic linkage between electronic
      databases and estimate of non-observed cases of microbiologically confirmed
      tuberculosis, using the 'capture-recapture method'. METHODS: the Piedmonti
      population was the study base. Tuberculosis cases were identified from the
      integrated Regional Tuberculosis Surveillance System (SSR- TB), the Tuberculosis
      Laboratory Registry (RL-TB), and the Regional Registry of Inpatient Records
      (SDO). RESULTS: 1790 cases of tuberculosis were recorded, in 28.6% (512) of the
      cases the disease was observed among individuals from countries with high
      prevalence of tuberculosis. Microbiologically confirmed cases of tuberculosis
      were 1254 (70%), while pulmonary cases were 1233 (69%). The annual crude
      incidence of tuberculosis (per 100,000 inhabitants) was 14.1 cases, 31.5% of whom
      were attributable to immigration from countries with high prevalence of
      tuberculosis. The incidence among immigrants was 122.4 cases, while that of
      microbiologically confirmed cases was 9.8 cases. The overall estimated
      sensitivity, for the microbiologically confirmed cases, was 97%, while the
      sensitivity of SSR-TB was 90%. CONCLUSIONS: Our estimate of tuberculosis
      incidence in Piedmont is about two times as great as that given by the WHO for
      Italy (8 cases per 100,000 inhabitants). The fraction of incident cases
      attributable to immigration from countries with high prevalence of tuberculosis
      is also consistent with that estimated in other industrialized countries
      undergoing high immigration flows. The integration of surveillance systems is
      essential to obtain accurate and timely estimates of the tuberculosis
      epidemiology.

PMID- 18717231
TI  - [Interval cancers as indicators of performance in screening programmes].
AB  - GISMa analyses the interval cancer (IS) topic providing guidelines and reference
      standards in addition to CE recommendations. IC identification is based on Cancer
      Registries (CR), if existing, or on hospital discharge records, in alternative.
      The optimal measure of IC frequency (inversely correlated with sensitivity) is
      the IC proportional incidence (observed IC/carcinomas expected in absence of
      screening). Other formulas (IC/IC + screen detected cancers; IC rate per 1000
      negative screens) look less reliable. IC stage at diagnosis (if available through
      CR) must be compared with screen detected cancer and cancer detected in non
      attenders. Review of mammograms preceding the IC (coded as screening error,
      minimal signs, or occult) should be done mainly with a blind procedure (IC mixed
      with negative controls), as this procedure is more representative of the original
      scenario and more respectful of radiologist's rights.

PMID- 18717232
TI  - [Mortality risk in intravenous drug users in Bologna and its determining factors.
      Results of a longitudinal study].
AB  - INTRODUCTION: this study shows the mortality rates in a retrospective cohort of
      intravenous drug users attending the public treatment centres (SERT), in the
      metropolitan area of Bologna, from 1978 to 2004 (3753 subjects, 2926 men and 827
      women). The overall mortality rate decreases after 1996 because of the
      substantial drop of mortality rate owing to AIDS. The overdose mortality
      increases until 1998 and then decreases; as from 1997 it becomes the first cause
      of death. The risk of death due to overdose is higher in men than in women, it is
      higher in subjects treated at SERT during the period 1996-2000 and decreases in
      subjects treated for more than two years. RESULTS: the study confirms an over
      mortality, due to all causes, of the cohort compared with the general population,
      in accordance with the results of other studies, and a remarkably high mortality
      for women (SMR in men: 1464; 95% CI 13.45-15.93; SMR in women: 25.61; 95% CI21.53
      30.45) as well. Major causes of death among men are, besides overdose and AIDS,
      cirrhosis, cardiovascular disorders, suicide, lung tumour, and road accidents;
      among women are suicide, cirrhosis and cardiovascular disorders. The risk of
      death is higher before 1996 with regard to subjects attending SERT before 1990,
      and to those who are in treatment for less than two years. Also at higher risk
      are those subjects with a low schooling level and unemployed.

PMID- 18717233
TI  - Semi-Bayes and empirical Bayes adjustment methods for multiple comparisons.
AB  - Epidemiological studies often involve multiple comparisons, and may therefore
      report many "false positive" statistically significant findings simply because of
      the large number of statistical tests involved. Traditional methods ofadjustment
      for multiple comparisons, such as the Bonferroni method, may induce investigators
      to ignore potentially important findings, because they do not take account of the
      fact that some variables are of greater a priori interest than others. The
      Bonferroni method involves "adjustings all of the findings to take account of the
      number of comparisons involved even though the a priori evidence may be very
      strong for some exposures, but may be much weaker (or non-existent)for the other
      exposures being considered. Furthermore, the Bonferroni method only "adjusts" for
      estimates of statistical signficance (p-values) and does not "adjust" the effect
      estimates themselves (e.g. odds ratios and 95% CI). Empirical Bayes and semi
      Bayes methods can enable the avoidance of numerous false positive associations,
      and can produce effect estimates that are, on the average, more valid. In this
      paper, we report on a research in which we applied these methods to a case
      control study of occupational risk factors for lung cancer and tested their
      performance.

PMID- 18717234
TI  - Why the consensus for consensus?

PMID- 18717235
TI  - Translating transition: a critical review of the diabetes literature.
AB  - Effective transition to an adult diabetes care provider is a significant
      component of care in adolescents with diabetes mellitus. During this period
      adolescents are at risk of dropping out of medical follow-up, an action which may
      interfere with their future physical and psychological well-being. The purpose of
      this paper is to review the diabetes literature as it pertains to transition
      including the outcomes, methods and patients' perceptions of the transition
      period. The results of the studies examined demonstrate a decrease in diabetes
      care visits following transition and that improvement in clinic attendance may be
      achieved through: (1) implementing an educational transition program; (2) having
      a transition care coordinator; and (3) having a young adult transition clinic
      attended by both adult and pediatric physicians. Despite the recognized
      importance of successful transition for adolescents with diabetes, studies on the
      subject remain sparse, highlighting the need for further research to determine
      both the magnitude of the problem as well as the impact of interventions to
      improve the processes of transition.

PMID- 18717236
TI  - Van Wyk Award acceptance speech.

PMID- 18717237
TI  - Pseudopuberty and juvenile hypothyroidism.

PMID- 18717238
TI  - Long-term follow-up of patients with congenital hyperinsulinism in Austria.
AB  - AIM: To assess the neurological and clinical long-term outcome of patients
      diagnosed with congenital hyperinsulinism (CHI) in Austria. PATIENTS AND METHODS:
      Fourteen patients diagnosed with CHI (1978-2000) were investigated
      retrospectively by reviewing hospital records. Thirteen of them were evaluated
      with either a questionnaire or clinical, neurological and biochemical
      investigations (age at evaluation 4.2-25.5 years) in a follow-up study in the
      year 2004. RESULTS: Fifty percent of the patients needed a pancreatectomy. The
      prevalence of mental retardation was 31%, of epilepsy 15% and of pancreatic
      insufficiency 14%. None of our patients had developed diabetes mellitus.
      Additionally the prevalence of obesity was 43% in patients after pancreatectomy.
      Sixty-nine percent of the patients had no further treatment at the time of follow
      up. CONCLUSION: Despite early diagnosis and intensive treatment, 31% of the
      patients presented with mental retardation.

PMID- 18717239
TI  - An analysis of predictive factors for the conversion from premature thelarche
      into complete central precocious puberty.
AB  - AIM: To determine the predictive factors for the conversion of premature
      thelarche (PT) into complete central precocious puberty (CCPP) in girls. DESIGN:
      Prospective. METHODS: One hundred and fifty-one girls with PT referred
      consecutively for evaluation of clinical, laboratory, and ultrasound data.
      RESULTS: Twenty-one and a half percent of girls with PT converted into CCPP at a
      chronological age of 7.1 +/- 0.7 years and bone age of 9.0 +/- 1.1 years. Using
      logistic regression analysis, longitudinal diameter of uterus (OR = 1.215),
      Tanner breast stage at the time of first physical examination (OR = 3.334) and
      regression of breast development (OR = 3.921) were the most significant variables
      predicting the conversion from PT into CCPP. Compared with the non-converted
      group, the converted groups had larger breast size at the time of diagnosis (z =
      2.077, p = 0.038). A total of 69.5% (105/151) of patients experienced complete
      regression of breast development, 13.2% (14/105) of whom converted into CCPP;
      21.5% (31/151) of patients had recurrent breast development, 32.3% (10/31) of
      whom converted into CCPP; 10% (15/151) of patients had constant breast
      development, 56.7% (7/15) of whom converted into CCPP, with the highest rate
      among the three breast development categories (chi2 = 12.23, p = 0.002).
      CONCLUSION: PT is not often a self-limited condition and may sometimes convert
      into CCPP. The predictive factors for conversion were related to estrogen
      exposure including longitudinal diameter of the uterus, Tanner breast stage at
      the first consultation and the regressive categories of breast development.

PMID- 18717240
TI  - Propylthiouracil associated antineutrophil cytoplasmic antibodies (ANCA) in
      patients with childhood onset Graves' disease.
AB  - Propylthiouracil (PTU) can induce anti-myeloperoxidase (MPO-ANCA) positive
      vasculitis. We performed a cross-sectional study to estimate the prevalence of
      MPO-ANCA in patients with childhood onset Graves' disease (GD) receiving PTU and
      to assess the relationship between ANCA and clinical manifestations of
      vasculitis. We studied 60 patients (59 girls and one boy) between 7.3 and 25.0
      years of age (mean +/- SD, 14.71 +/- 4.49). GD, diagnosed at the age of 3.0 to
      14.5 years (11.3 +/- 2.48), was designated as: newly diagnosed, on PTU therapy,
      and after PTU discontinuation in 4, 50 and 6 patients, respectively.
      Manifestations of vasculitis were noted and the patients were tested for MPO
      ANCA, antinuclear antibodies, blood urea nitrogen, creatinine and urine analysis.
      Twenty-six patients (43.3%) reacted positively for MPO-ANCA, 23 were on PTU
      therapy (0.42 to 6.00, median 3.00 years) and three had discontinued PTU. There
      were 34 (56.7%) ANCA-negative patients and 27 patients on PTU therapy (0.25 to
      5.17, median 1.00 years, p = 0.012). Vasculitis presented in 16 patients (26.7%),
      all of whom were receiving PTU at the time of the study. The percentage of
      vasculitis among MPO-ANCA positive patients was 27.6% more than in the negative
      group, p = 0.017. PTU was discontinued in patients with vasculitis and positive
      for MPO-ANCA. Our findings show a high prevalence of MPO-ANCA positivity and a
      significantly higher percentage of vasculitis among these patients, suggesting
      that patients taking PTU should be closely observed for the appearance of MPO
      ANCA and signs of vasculitis, especially patients GD who have been treated for a
      long time.

PMID- 18717241
TI  - Molecular analysis of the AR and SRD5A2 genes in patients with 46,XY disorders of
      sex development.
AB  - The aim of this study was to assess the clinical and endocrinological features,
      and to analyze AR and SRD5A2 genes in patients with 46,XY disorders of sex
      development (DSD). This study included 20 patients from 19 families showing
      clinical features of 46,XY DSD. Molecular analysis was performed of the AR and
      SRD5A2 genes, as well as endocrinological evaluations, such as 17a
      hydroxyprogesterone, plasma renin activity, aldosterone, adrenocorticotropic
      hormone and hCG stimulation test. Out of 20 patients with 46,XY DSD, only one
      (5%) displayed androgen insensitivity syndrome (AIS), and four (20%) were 5alpha
      reductase deficient by mutation analysis. The patient with AIS revealed
      significant elevation of serum testosterone following hCG stimulation. The
      patient with 5alpha-reductase deficiency with a homozygous p.R246Q mutation had a
      low basal dihydrotestosterone level. The patient with p.Q6X/p.R246Q mutations
      showed a moderately elevated testosterone/dihydrotestosterone ratio following hCG
      stimulation. Endocrinological tests are not reliable for the etiological
      diagnosis of AIS and 5alpha-reductase deficiency due to variable reference ranges
      of hormonal profiles according to the age and the severity of the enzyme defect.
      DNA analysis may be employed as a tool for the early and precise diagnosis of
      patients with 46,XY DSD, and genetic counseling can be used for families at risk.

PMID- 18717242
TI  - Efficacy and safety of inhaled human insulin (Exubera) compared to subcutaneous
      insulin in children ages 6 to 11 years with type 1 diabetes mellitus: results of
      a 3-month, randomized, parallel trial.
AB  - AIM: To compare the efficacy and safety of Exubera (EXU) with subcutaneous (SC)
      insulin in children, ages 6-11 years, with type 1 diabetes mellitus. DESIGN AND
      METHODS: 121 children were randomized to receive EXU or SC insulin, plus
      intermediate/long-acting insulin for 12 weeks. Change in HbA1c was the primary
      efficacy endpoint. RESULTS: Decreases from baseline HbA1c were comparable between
      treatment groups (difference between adjusted mean decrease from baseline [EXU-SC
      insulin], -0.23 [95% CI, -0.49, 0.03]). Differences between groups on pulmonary
      function tests were small and not significant. Mild to moderate cough occurred in
      24.6% of EXU versus 6.8% of SC insulin patients. The risk for hypoglycemia was
      comparable between EXU and SC insulin (relative risk 0.88 [95% CI, 0.71, 1.11]).
      Increased insulin antibodies with EXU were not associated with clinical findings.
      CONCLUSION: The efficacy and safety profiles shown in this study are the
      foundation for further investigation of EXU in this population.

PMID- 18717243
TI  - Usefulness of growth hormone (GH) stimulation tests and IGF-I concentration
      measurement in GH deficiency diagnosis.
AB  - The diagnosis of growth hormone (GH) deficiency (GHD) is still problematic for
      the clinician. There is no gold standard for estimating GH secretion. The aim of
      this study was to compare the diagnostic usefulness of spontaneous GH secretion
      test, pharmacological tests with insulin, clonidine, L-dopa, and glucagon, and
      IGF-I measurement in GHD. We studied 180 prepubertal, short children. Predictive
      values were calculated for different GH cutoff levels for each diagnostic test.
      ROC curves were used to estimate the diagnostic usefulness of the tests. The
      results show that sleep is the strongest stimulatory agent for GH secretion. The
      estimation of GH secretion after onset of sleep can be used as a screening test
      in GHD diagnosis. The insulin test has the highest discrimination. A combination
      of insulin test with another provocative test allows high discrimination and
      accuracy for standard cut-off GH level. Measurement of IGF-I is characterized by
      low predictive values. IGF-I level below the mean according to age indicates high
      probability of GHD. Auxological parameters should be the most important factor in
      diagnosing GHD.

PMID- 18717244
TI  - Hyperglycemia and hypoinsulinemia in patients with Fanconi-Bickel syndrome.
AB  - Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder
      characterized by the combination of hepatorenal glycogen accumulation and Fanconi
      type nephropathy. Mutations in GLUT2, the gene for facilitative glucose
      transporter protein 2 (GLUT2), cause FBS. AIM: To evaluate glucose and insulin
      responses to oral glucose load in patients with FBS. METHODS: Ten children (7.3
      +/- 4.8 years) diagnosed with FBS in early infancy underwent a standard oral
      glucose tolerance test (OGTT); plasma glucose (PG) and serum insulin
      concentrations were measured at 30-min intervals for 2 hours. HbA1c, insulin-like
      growth factor-I, and fasting lipid profiles were also measured. RESULTS: Mean
      fasting and 2-h PG concentrations were 3.8 +/- 0.9 mmol/l and 8.6 +/- 3.0 mmol/1,
      respectively. 2-hour PG levels were above 11.1 mmol/l in two patients (20%) and
      between 7.75 and 11.1 mmol/ in four patients (40%). HbA1c was normal in all the
      patients with a mean of 5.4 +/- 0.3%. Mean fasting and peak serum insulin levels
      were 8.7 +/- 0.8 pmol/ and 98.6 +/- 43.0 pmol/l, respectively, and did not differ
      between the patients with normal and abnormal OGTT. Patients with abnormal OGTT
      were younger (4.8 +/- 3.2 vs 11.0 +/- 4.8 yr; p = 0.04). Fasting PG increased
      with age (r = 0.80, p < 0.01). Total and LDL cholesterol as well as triglyceride
      concentrations were elevated. CONCLUSIONS: Most but not all patients with FBS
      have impaired glucose tolerance/diabetes range hyperglycemia after OGTT while
      maintaining normal HbA1c. Patients with FBS are relatively hypoinsulinemic. Both
      fasting hypoglycemia and post-OGTT hyperglycemia seem to improve with age.

PMID- 18717245
TI  - Glycogen storage disease type IIIa presenting as non-ketotic hypoglycemia: use of
      a newly approved commercially available mutation analysis to non-invasively
      confirm the diagnosis.
AB  - Glycogen storage disease type III (GSD-III) is an autosomal recessive disorder
      caused by the lack of amylo-1,6-glucosidase (AGL), one of the catalytic domains
      of the glycogen debranching enzyme. Deficiency of this enzyme classically results
      in hepatomegaly and ketotic hypoglycemia. The diagnosis of the disorder was
      previously confirmed with a liver biopsy demonstrating abnormal liver glycogen
      content and absent enzyme activity. We describe an 11 month-old African-American
      Jehovah's Witness male with non-ketotic hypoglycemia (NKH), hepatomegaly,
      cardiomyopathy, and a flat glucagon response confirmed to have GSD-IIIa by
      mutation analysis of the AGL gene. The present case represents an unusual
      presentation (NKH) of GSD-IIIa and emphasizes the utility of the newly approved
      commercially available Clinical Laboratory Improvement Advisory Committee (CLIA)
      mutation analysis test.

PMID- 18717246
TI  - Clinical and laboratory findings of two newborns with Wiedemann-Rautenstrauch
      syndrome: additional features, evaluation of bone turnover and review of the
      literature.
AB  - Wiedemann-Rautenstrauch syndrome (WRS) is a rare autosomal recessive condition
      which represents a complex of symptoms and laboratory findings with unknown cause
      and pathogenesis. Approximately 30 patients with WRS have been reported. We
      report here two newborns with WRS from Turkey with clinical and laboratory
      findings including bone marker evaluation. Our two patients had characteristic
      features of WRS, including intrauterine growth retardation, aged appearance, near
      absence of subcutaneous fat, gluteal fat pads, also labial pad in the first
      infant, wrinkled thin skin, sparse scalp hair, prominent scalp veins and facial
      dysmorphism. They also have severe osteopenia and elevated urinary
      deoxypyridinoline levels which have not been previously described in patients
      with WRS. Impaired lipid and hormone profiles including elevated prolactin and
      triglyceride level have been reported in patients with WRS. Our first patient
      also has excessive joint contractures, persisting thrombocytosis and rectal
      prolapse. We evaluated bone mineral findings in our two patients with WRS and
      recommend caution when handling children with WRS.

PMID- 18717247
TI  - Congenital nephrotic syndrome and persistent hypothyroidism after bilateral
      nephrectomy.
AB  - Congenital nephrotic syndrome is commonly associated with hypothyroidism. Thyroid
      hormone supplementation is recommended as standard of care. The hypothyroidism is
      postulated to occur secondary to chronic massive proteinuria with loss of thyroid
      binding globulin, thyroid hormone and iodine. Previous reports have indicated
      that thyroxin may be discontinued following bilateral nephrectomy. We report our
      experience with one child with congenital nephrotic syndrome, Finnish type, and
      hypothyroidism who had a high requirement for thyroxin (100-150 microg/d) from
      infancy to 4 years of age. Hypothyroidism persisted despite bilateral nephrectomy
      and later following renal transplantation. However, his thyroxin requirement is
      now substantially lower (62.5 microg/d) at age 14 years. No goiter was detected
      clinically and antithyroid antibodies were negative. Thyroid ultrasound and 123I
      scan revealed a thyroid gland in the anatomically normal location. 123I uptake
      was elevated, 18% at 6 hours and 51% at 24 hours (normal values: 3-16% at 6 hours
      and 8-25% at 24 hours). Perchlorate was unavailable for a perchlorate washout
      study. We speculate that this patient may have an intrinsic problem with thyroid
      hormone synthesis. It is unclear whether this is related or coincidental to the
      Finnish nephrotic syndrome. We recommend following thyroid functions closely if
      thyroxin is discontinued following bilateral nephrectomies in Finnish type
      congenital nephrotic syndrome.

PMID- 18717248
TI  - Relationship between endothelial dysfunction, carotid artery intima media
      thickness and circulating markers of vascular inflammation in obese hypertensive
      children and adolescents.

PMID- 18717249
TI  - The incidence of glucose disorders related to cystic fibrosis could be higher
      with current criteria.

PMID- 18717250
TI  - Risk versus choice: what teens need to know about alcoholism.

PMID- 18717251
TI  - A serious condition or a benign masquerade? Mycosis fungoides.

PMID- 18717252
TI  - Substance abuse: screening, diagnosis, management.

PMID- 18717253
TI  - Inherited epidermolysis bullosa: this dermal disease is beyond skin deep.

PMID- 18717254
TI  - Kyphoplasty for osteoporotic vertebral compression fractures.

PMID- 18717255
TI  - Pericardial effusion and developing tamponade in a 30-year-old man.

PMID- 18717256
TI  - The ZZZs to success: a good night's sleep is more than beauty rest.

PMID- 18717257
TI  - What's the best sun protection to use?

PMID- 18717258
TI  - Patient information. What's the best sun protection to use?

PMID- 18717259
TI  - Chest pain and an abnormal ECG in a young woman. Coarctation of the aorta.

PMID- 18717260
TI  - Case of the month. Late effect of intracranial injury without mention of skull
      fracture.

PMID- 18717261
TI  - [Future prospects in developing of dengue vaccines].
AB  - Dengue is a viral, febrile and acute disease that causes more morbility than any
      other infection for Arbovirus. It becomes necessary to implement a safe and
      effective vaccine that will contribute to the eradication of this disease,
      especially in endemic areas with very low socio-economic conditions. The only
      option that exists at the present to control the transmission of the disease is
      through vector control. So far, there are no effective antiviral drugs for
      flavivirus such as dengue. Candidates for vaccines for this disease, who are
      currently in advanced stages of development, are live attenuated vaccine, live
      attenuated chimerics, inactivated virus, subunits and DNA, in order to mimic the
      natural infection. The requirements for an ideal vaccine capable of protecting
      the population at risk should be: free reactogenicity, one which induces
      protection against all four serotypes of the virus (tetravalent), that offers
      effective prolonged protection; it also should be highly immunogenic, with few
      side effects, easy administration, available at low cost and should be
      administered in one dose, both in adults and in children. Meanwhile, efforts to
      try to give immunoprophylaxis for this disease continue, in order to design an
      ideal vaccine allowing the eradication of the disease and the reduction in the
      number of cases which affects our people every day.

PMID- 18717262
TI  - [A confirmatory diagnosis of antibodies anti-Trypanosoma cruzi in donors referred
      by blood banks in Venezuela].
AB  - To establish the confirmatory diagnosis of Trypanosoma cruzi infection, at least
      two immunoserological tests (ELISA, Indirect hamaglutination, IH, Complement
      Fixation Test, CFT) were carried out in 254 donors, from public and private blood
      banks of Venezuela, during 48 months between 1997-1998 and 2003-2004, referred to
      the Immunology Section of the Tropical Medicine Institute in Caracas. Antibodies
      anti-T. cruzi were detected in 129/254 (50,79%) by ELISA-IgG or IH and CFT. The
      "artificial xenodiagnosis" was positive in 10/118 persons with positive confirmed
      serology. Of 129 donors found positive by the serological tests, 68 were living
      in the capital region and 61 in the interior of the country. Likewise 113 were
      born in the interior of the country, 8 in Caracas and 8 in Colombia. Of them, 12
      individuals serologically confirmed declared to have donated blood in a minimum
      of 4 occasions before diagnosis. The present study emphasizes the importance of
      detection of antibodies against T. cruzi in the integral evaluation of blood
      donors, since many of them with antibodies anti-T. cruzi, have donated blood
      several times previous to diagnosis.

PMID- 18717263
TI  - [Altered expression of survival (CD127) and death (Fas) receptors in total, naive
      and memory CD8 T lymphocytes from human immunodeficiency virus infected patients:
      possible implications for progression of infection].
AB  - We studied the ex vivo and in vitro expression of CD95/Fas and CD127 receptors in
      total, naive and memory CD8+ T cells from HIV infected patients with different
      blood counts of CD4+ T cells. In addition, spontaneous and induced apoptosis were
      determined in vitro using a viral antigen (Env), along with an evaluation of
      their specific proliferative capacity. The obtained results demonstrated that
      patients with low counts of CD4+ T cells (CD4 < 250/microL), showed ex vivo, a
      high expression of CD95/Fas and a low expression of CD127 in all CD8+ T cell
      subgroups, as compared with patients with bigger counts of CD4+ T cells in blood
      (CD4> 250/microL). In vitro analyses using Env antigen showed that CD8+ T cells
      displayed a similar expression of both receptors, with a higher incidence of
      spontaneous and induced apoptosis and a diminished proliferative capacity as
      compared with controls. Results indicate how the progression of VIH infection in
      non-treated patients is related to a decrease of CD8+ T cells in blood,
      characterized by failures in their proliferative capacity and apoptosis
      frequency, which is demonstrated by the altered expression of CD127 and CD95/Fas
      expression.

PMID- 18717264
TI  - [Glucose-6-phosphatase from nuclear envelope in rat liver].
AB  - Nuclear envelope (NE) and microsomal glucosa-6-phosphatase (G-6-Pase) activities
      were compared. Intact microsomes were unable to hydrolyze mannose-6-phosphate (M
      6-P), on the other hand, intact NE hydrolyzes this substrate. Galactose-6
      phosphate showed to be a good substrate for both NE and microsomal enzymes, with
      similar latency to that obtained with M-6-P using microsomes. In consequence,
      this substrate was used to measure the NE integrity. The kinetic parameters (Kii
      and Kis) of the intact NE G-6-Pase for the phlorizin inhibition using glucose-6
      phosphate (G-6-P) and M-6-P as substrates, were very similar. The NE T1
      transporter was more sensitive to amiloride than the microsomal T1. The
      microsomal system was more sensitive to N-ethylmalemide (NEM) than the NE and the
      latter was insensitive to anion transport inhibitors DIDS and SITS, which
      strongly affect the microsomal enzyme. The above results allowed to postulate the
      presence of a hexose-6-phosphate transporter in the NE which is able to carry G-6
      P and M-6-P, and perhaps other hexose-6-phosphate which could be different from
      that present in microsomes or, if it is the same, its activity could by modified
      by the membrane system where it is included. The higher PPi hydrolysis activity
      of the intact NE G-6-Pase in comparison to the intact microsomal, suggests
      differences between the Pi/PPi transport (T2) of both systems. The lower
      sensitivity of the NE G-6-Pase to NEM suggests that the catalytic subunit of this
      system has some differences with the microsomal isoform.

PMID- 18717265
TI  - [Effect of hypocapnia/alkalosis on the fluid filtration rate in isolated and
      perfused rabbit lungs].
AB  - Hypocapnia/alkalosis is a consequence of several lung and metabolic pathologies.
      The aim of this study was to determine whether the increase of fluid filtration
      rate (FFR) that occurs during Hypocapnia/alkalosis circumstances is determined by
      hypocapnia, alkalosis or both. 7 groups were formed (N=36) using isolated rabbit
      lungs. Group 1: Control (PCO2 6%, pH: 7.35-7.45); Group 2 (n=6):
      Hypocapnia/Alkalosis (CO2 1%, pH: 7.9); Group 3 (n=6): Hypocapnia/Normo-pH (CO2
      1% pH 7.35-7.45), Group 4 (n=6) Normocapnia/Alcalosis (CO2 6%, pH: 7.9).
      Fenoterol, papaverine and hydrocortisone were added to Groups 5, 6 and 7 (n=4)
      respectively, all under Normocapnia/Alkalosis. FFR and Pulmonary Arterial
      Pressure (Pap) were considerably higher in group 2 than in control (FFR:
      1.92g/min +/- 0.6 vs 0.0 g/min +/- 0.006). A strong influence exerted by pH was
      observed when Group 3 and group 4 were compared (FFR: 0.02 g/min +/- 0.009 vs 2.3
      g/min +/- 0.9) and (Pap: 13.5 cmH2O +/- 1.4 vs 90 cmH2O +/- 15). A reduced effect
      was observed in groups 5 and 6 (papaverine and hydrocorisone) and a totally
      abolished effect was observed in group 7 (fenoterol) (FFR: 0.001 +/- 0.0003
      mL/min and Pap: 14 +/- 0.8 cmH2O). Pulmonary edema induced by
      Hypocapnia/alkalosis is a consequence of alkalosis and not of hypocapnia. This
      effect could be due to inflammatory damage in the lung parenchyma and alkalosis
      mediated vasoconstriction.

PMID- 18717266
TI  - [Dual diagnosis in psychiatric inpatients: prevalence and general
      characteristics].
AB  - Comorbidity between a substance use disorder (SUD) and another psychiatric
      disorder is known as dual diagnosis. It is of great relevance due to its
      important clinical consequences and costs of care. There are practically no
      published studies on dual diagnosis prevalence in patients admitted to
      psychiatric hospitalization units in general hospitals (PHUGH) in our country.
      The objectives were to estimate the prevalence of dual diagnosis in psychiatric
      inpatients admitted consecutively to a Psychiatric Hospitalization Unit (Hospital
      Universitario 12 de Octubre, Madrid, Spain) in one year, to compare clinical and
      sociodemographic variables between the dual diagnosis group (DD group) and the
      group with a psychiatric disorder but no SUD (PD group), and to study the types
      of substances used. This is a retrospective study, based on the review of the
      clinical charts of the 257 patients admitted to this PHUGH in one year. The
      results showed that, excluding nicotine dependence, 24.9% of our inpatients had a
      SUD as well as another psychiatric disorder. A statistically significant
      predominance of men was found in the DD group, as well as a younger age at the
      time of the study, at the beginning of their psychiatric attention and on their
      first psychiatric admission, and they had received diagnoses of schizophrenia or
      related psychoses more often than the PD group, who had mostly affective
      disorders. The substances most frequently used in the DD group were alcohol
      (78.1%), cannabis (62.5%), and cocaine (51.6%). Due to the high prevalence and
      repercussions of dual diagnosis, it would be advisable to have specialized
      therapeutic programs for its treatment.

PMID- 18717267
TI  - The cholinergic system in cyclophosphamide-induced Chagas dilated myocardiopathy
      in Trypanosoma-cruzi-infected rats: an electrocardiographic study.
AB  - Chronic Chagasic Cardiomyopathy (CCC) has been related to the cholinergic system
      by the neurogenic and autoimmune theories. The neurogenic theory explains
      cardiomyopathy as a result of post-ganglionic parasympathetic denervation.
      Cyclophosphamide (CP) facilitates the development of autoimmune disease because
      of a selective depletion of suppressor T cells. In this study we characterized
      the phenylephrine-induced vasovagal reflex using selective cholinergic drugs, in
      two rat models: Trypanosoma cruzi (TC) infected animals and CCC CP-treated rat
      model. To achieve this goal, 3 week old-90 Sprague Dawley rats were divided into
      four groups: Control (C), CP, TC and TCCP; TC and TCCP were inoculated with 1000
      trypomastigotes/g; CP and TCCP were treated with CP 20 mg/Kg twice a week for
      five times. After 6 months, the studied animals underwent electrocardiographic
      (EKG), radiographic (Rx) and histopathological (HP) assesments. The vagal
      integrity was evaluated by application of phenylephrine (PE) plus tacrine, while
      the muscarinic cholinergic function was evaluated using selective M1, M2, M3 and
      M4 muscarinic antagonists. Our data show show that TCCP rats displayed the
      highest frequency of EKG, Rx and HP disturbances. TC and TCCP rats exhibited a
      decreased response to: 1) phenylephrine-induced vagal baroreflex bradycardia; 2)
      methoctramine-, 4-DAMP- and tropicamide-induced tachycardia; 3) methoctramine
      induced QRS shortening, and 4) tropicamide-induced QT prolongation. In
      conclusion, CP facilitates the development of CCC in Trypanosoma cruzi infected
      rats, by promoting parasympathetic disturbances that appear as consequence of
      alterations on the muscarinic receptor distribution at different neural
      integration levels.

PMID- 18717268
TI  - [Epidemiologic and molecular study of Entamoeba histolytica and Entamoeba dispar
      strains in pacients with diarrhea in Cumana, Sucre state, Venezuela].
AB  - An epidemiological and molecular study on E. histolytica and E. dispar was
      carried out in 428 patients with gastrointestinal symptomatology of diarrhea from
      different health centers in Cumana, Sucre state. The samples were processed
      through: direct examination with 0.85% physiological saline solution, temporal
      lugol staining, trichromic staining and the Ritchie method of concentration; a
      sucrose gradient was used for cyst isolation. The small subunit of the 16S RNA
      was amplified by nested, multiplex PCR for the molecular detection. The E.
      histolytica/E. dispar prevalences according to the direct, Ritchie and trichromic
      staining methods were 20.09, 13.79 and 12.15%, respectively; while prevalences
      according to PCR for E. histolytica and E. dispar were 6.31% and 4.44%,
      respectively, also detecting four cases of mixed infection. Sequencing of the
      amplified fragments of E. histolytica showed 100% homology with the sequences
      with strains from Merida (Venezuela), USA, Brazil, Mexico and GenBank. The
      infections by E. histolytica and E. dispar were statistically associated with age
      but not with sex. The presence of mucus, blood and abdominal pain were only
      associated to E. histolytica infection. The moderate prevalence of E. histolytica
      shows the endemic status of this population and warns about the potential problem
      as a morbidity and mortality in Sucre state. The frequency of E. dispar in this
      population suggests the existence of an overestimation problem in the diagnosis
      of amoebiasis with its clinical and epidemiological implications, and shows the
      poor knowledge about the true prevalences of this protozoan. The PCR allowed for
      the differential identification of E. histolytica and E. dispar, as well as the
      presence of mixed infections, making a great tool for epidemiological amoebiasis
      studies.

PMID- 18717269
TI  - [Aplication of demineralized human bone matrix in the surgical dental fusion
      treatment. Report of a case].
AB  - The purpose of this work is to present a surgical alternative in the treatment of
      the dental fusions through the placement of demineralized human bone matrix
      (DHBM) (Grafton Putty)*, immediately after the separation and extraction of the
      fused tooth to the permanent one. The dental fusion is a dental anomaly of union,
      that consists in the union of two dental germs during development. It could
      happen at any of the dental germ evolution stages from the dental sheet or from
      more advanced processes of differentiation. For the clinical treatment, an
      allograft of DHBM with osteoinductive and osteoconductive properties was used.
      This had several factors of bone growth, it allowed the gradual growth of a new
      bone that helped to correct the bone defects post-extraction and to cover the
      exposed distal wall of the remaining permanent tooth. The clinic evaluation and
      the periapical and panoramic radiographies images were used for the clinical
      control. It can be concluded that the surgical separation and the extraction of
      the tooth with less anatomical likeness to the contralateral and the placement of
      the DHBM, represent a surgical treatment alternative of the dental fusion.

PMID- 18717270
TI  - Berardinelli syndrome. A case report with fatal outcome.
AB  - The aim of this paper is to present the main clinical findings and evolution of a
      fatal case of Berardinelli Syndrome (congenital generalized lipodystrophy). A 15
      year-old girl, followed since the age of three months in the Genetic outpatients'
      clinic, developed insulin resistance when she was eight years old. She had
      hyperchloremic metabolic acidosis, bilateral retinopathy, proteinuria and
      hydronephrosis. She was hospitalized several times due to urinary infections. In
      her last admission she had fever, abdominal pain and was diagnosed urinary
      sepsis. She presented hemodynamic instability and died, despite all therapeutic
      measures adopted. Considering the rarity of this syndrome it is important to
      describe the clinical presentation and evolution of this patient with
      Berardinelli Syndrome, which developed renal dysfunction and had a fatal outcome.

PMID- 18717271
TI  - [Pulmonary paragonimiasis. Case report].
AB  - Paragonimiasis is a zoonosis affecting wild and domestic animals and human
      beings, caused by species of trematodes of the genus Paragonimus. Humans become
      infected after ingestion of raw or poorly cooked fresh water crustaceans. The aim
      of the present work is the description of a case of a 3-years old child, coming
      from Guarico State in Venezuela with a year of residence in the seashore of the
      Provincia Manabi in Ecuador, where he ate crabs in "ceviche". During
      hospitalization, he presented respiratory distress, hepatomegaly and nodules in
      the back. The thorax cat scan showed heavy infiltrate in both pulmonary bases and
      pleural compromise. Based on clinic, radiological images, an eosinophilia of 47%
      (Eosinophils absolute count (EAC) 6.682/mm3) and the antecedent of raw crabs
      ingestion, pulmonary paragonimiasis was diagnosed. Paragonimus eggs were not
      found in sputum and feces. ELISA with crude Paragonimus antigen was positive and
      Western blot revealed recognition of specific molecules. After treatment for
      three days with Praziquantel at a daily dose of 25 mg/kg body weight divided into
      three intakes, the sintomatology disappeared and radiological images and number
      of eosinophils diminished considerably.

PMID- 18717272
TI  - [Amebiasis: importance of the diagnosis and treatment. Minireview].
AB  - The protozoa E. histolytica is the etiologic agent of human amebiasis, the
      identification of its pathogenicity has been of great aid in the search of
      important antigens for immunodiagnostic and inmunoprofilaxis. In 1995 the
      isolation and axenization of the first two strains of Venezuelan E. histolytica
      were described from symptomatic patients, which were denominated: IULA 1092:1 and
      IULA: 0593:2 These strains have been evaluated through studies of electrophoretic
      profiles, demonstrating the presence of type II zymodemes, characteristic of
      pathogenic strains. Also, they have shown to be of high virulence, they present a
      complex pattern of reactivity and the presence of a marker antigen of
      pathogenicity. The isoenzymatic analysis has shown correlation with the genotypic
      analysis, showing a genotypic organization typical of a pathogenic strain. With
      this strain, it has been possible to evaluate all the amebiasis cases sent to the
      Institute of Clinical Immunology of Universidad de Los Andes, in Merida,
      Venezuela. These strains have been useful, here, as well as in other sites, when
      using their antigens to evaluate urban and even indigenous populations. They can
      be used, like native strains of reference, in diagnostic tests and prophylaxis
      for this parasitosis. The limitations of the microscopic analysis, specifically,
      the false amebiasis diagnosis and its inability to discriminate between
      infections caused by E. histolytica and E. dispar have led to the development of
      laboratory procedures that allow for the detection of components of the species
      present. The success of such procedures would result in a diminution of
      unnecessary treatments, which could be the cause of antiamoebic drug resistance.

PMID- 18717273
TI  - [Role of the spleen in immunity. Immunologic consequences of splenectomy].
AB  - The spleen is a lymphatic organ that plays a fundamental role in protecting the
      body from invading pathogens. Being an organ that is interposed in the blood
      stream, it also stands as the body's largest blood filter that furthermore brings
      contribution to detecting senescent, mechanically damaged and aberrant cells. The
      spleen combines the innate and adaptive immune system in a unique way, releasing
      an immediate innate reaction to microbial penetration, but also an adaptive
      immune response that involves the interaction of cells that recognize a
      particular antigen, implicating MHC molecules presented by antigen-presenting
      cells. Clinical manifestations of some hematologic conditions can be controlled
      by splenectomy. The use of this procedure, although, has been restricted due to
      many observations of overwhelming post-splenectomy bacterial infections in
      splenectomized patients. After splenectomy, the mechanisms that play a
      fundamental role in bacterial clearance are altered, leading to gram-positive,
      but also gram-negative sepsis. Subtotal splenectomy is, therefore, a logical
      alternative that controls the manifestations of hematologic diseases while
      maintaining splenic function.

PMID- 18717274
TI  - [Guidelines for the management of painful endometriosis].
AB  - OBJECTIVE: To establish guidelines for the medical and surgical management of
      painful endometriosis. MATERIAL AND METHODS: An exhaustive review on Medline and
      Cochrane Database between 1980 and 2006 was performed. RESULTS: GnRH agonists,
      progestins, continuous monophasic oral contraceptives and danazol have a
      suppressive effect on dysmenorrhoea, nonmenstrual pain and dyspareunia (grade A).
      Surgical treatment is effective in painful endometriosis (grade B). Complete
      surgical excision of deep endometriotic lesions with conservation of uterus and
      ovaries has a limited term efficacy on pain relief (grade C). A multidisciplinary
      approach is recommended (grade C). The use of the psychotherapy improves the
      management of chronic pain (grade A). There is a lack of information concerning
      the therapeutic strategy able to prevent recurrences. Whether endometriosis
      recurrences occur, medical treatment should be the first line approach (expert
      opinion). A hysterectomy with salpingo-oophorectomy and complete excision of the
      lesions is efficient in women with pain recurrence who no longer desire pregnancy
      (grade C). CONCLUSIONS: Medical and surgical treatments have a limited term
      efficacy on painful endometriosis (grade A). The benefit/risk ratio, depending on
      side-effects, should be assessed on a case to case basis.

PMID- 18717275
TI  - [Pancreaticoduodenectomy in elderly patients--a safe operation?].
AB  - The aim of this study was to analyze the impact of age in mortality and morbidity
      after duodenopancreatectomy (DPC), setting the age of 70 as a cut-off. A
      retrospective study was made of two groups of patients (under 70 and over 70
      years old) who underwent DPC in the Center of General Surgery and Hepatic
      Transplantation, Fundeni, Bucharest between 2001 and 2006 for malignant and
      benign tumors of the pancreatic head, distal biliary tract, duodenum, Vater's
      ampulla and chronic pancreatitis. 245 DPC were performed, 207 in patients under
      70 years old (group A) and 38 in patients over 70 years old. Postoperative global
      morbidity rate was 58% in group B vs 49,9 % in group A. Postoperative mortality
      rate was 5,2% in group B and 4,8 % in group A. No significant differences were
      recorded in survival when comparing the two groups, both in pancreatic head
      cancer or distal biliary tract cancer. Under these circumstances, increased age
      is not determining an increase in postoperative mortality after DPC, but is
      associated with a higher risk of postoperative medical complications.

PMID- 18717276
TI  - [Surgical emergencies in elderly].
AB  - BACKGROUND: A higher number of elderly are seeking surgical care in the last
      years for different affections. The aim of the study was to analyze the
      characteristics of surgical emergency pathology in elderly and to establish
      several prognostic factors. MATERIALS AND METHODS: We did a retrospective study
      on 22.803 patients admitted in the First and the Third Clinic of Surgery from
      Targu-Mures between 1999 and 2006. The data were statistically processed.
      RESULTS: The elderly (> or =70 years) represented 15.10% of all cases and 20.70%
      of all emergencies. Almost half of them (47.80%) were admitted in emergency
      conditions, compared to only a third (32.53%) of the younger group. The
      malignancies represented 16.72%, meanwhile in the younger group only 6.98 %.
      Abdominal emergencies represented 83.59%, mostly due to intestinal occlusion and
      digestive hemorrhages. The operability ratio was 68%, close to the younger group
      (72%). The global mortality rate was 3.95%. CONCLUSIONS: Surgical emergencies
      affect elderly in a higher percentage than the younger group. The emergency
      condition, the elder age and neoplasia are the most important factors of negative
      prognosis, and more important when they cumulate, increasing the mortality rate
      up to fivefold compared to the elderly admitted in elective condition.

PMID- 18717277
TI  - Long-term results of surgical treatment in Graves' disease orbitopathy. Is there
      a correlation between the extent of thyroidectomy and the course of orbithopathy?
AB  - The place of thyroidectomy in the management of the Graves' disease patients with
      endocrine orbitopathy (EO) is still controversial. The aim of this study was to
      evaluate the course of EO according to the extent of thyroid resection. METHODS:
      A retrospective cross-sectional study was performed on a series of 171 cases of
      Graves'disease, operated in the period 1987-2002 in the Department of Surgery of
      the Philipps University, Marburg. The severity of EO at the time of operation was
      assessed according to NOSPECS classification and a structured telephone interview
      was conducted in order to appraise the long term results. RESULTS: Complete data
      acquisition was possible in 153 patients (89%). There were 123 women with a
      median age of 36 years (range 10-75) and 30 men with a median age of 33 years
      (range 22-65). Concerning the severity of EO, 70 patients (45.8%) had no ocular
      symptoms (group I). The 83 patients with clinical eye disease were divided in
      group II--63 patients (76%) with moderate syndrome and group III--20 patients
      (24%) with marked symptoms of EO. 12 patients received total thyroidectomy, 96
      had Dunhill-resection and in 45 patients subtotal resection was performed. A
      median follow-up period of 96 months (range 12-216 months) was recorded. Post
      operatively, of the 83 patients with EO, 53 patients (63.8%) declared an
      improvement of EO, in 29 patients (34.9%) the disease was stable and only one
      patient declared the worsening of EO. The extent of thyroid resection did not
      correlate with the postoperative course of orbitopathy. CONCLUSION: Thyroid
      surgery for GD improves the course of EO, independent of the extent of resection.

PMID- 18717278
TI  - Evaluation and surgical management of the gallstone ileus. A single center
      experience.
AB  - Gallstone ileus representing 1-4% of all bowel obstructions cholelithiasis.
      Impaction of a gallstone in the human of the bowel is a surgical emergency.
      Relief of the obstruction is the treatment of choice, but controversy exists
      regarding the repair of the fistula and cholecystectomy. Our experience in the
      management of gallstone ileus is presented in the following article.

PMID- 18717279
TI  - [Renovascular hypertension: symptoms and signs. Clinical study on 20 patients].
AB  - OBJECTIVES: symptoms in renovascular hypertension can be wrong interpreted, which
      leads to a late diagnostic, after discover the determination disease. MATERIALS
      AND METHODS: the study on the renovascular hypertension was made on 20 patients,
      aged between 2 and 36 years old, diagnosed with reno-ureteral malformations,
      pyelonephritis, reno-ureteral reflux and renal trauma as a determination disease,
      leads to manifestation types that guide the diagnostic: neuro-psychiatric signs,
      weight loss, renal signs and digestive signs. Beginning from these signs the
      arterial hypertension was diagnosed and the investigations determined the causes.
      RESULTS: Periodic postoperative evaluation at 3 months, during a period between 4
      months and 7 years, individualised 4 evolutional clinical types: AHT with lumbar
      pain, AHT with no clinical signs, AHT with ophthalmologic signs and AHT with
      encephalitis like signs. CONCLUSIONS: symptoms in renovascular hypertension don't
      have pathognomonic clues and the identified signs, one type or all together,
      enforce the evaluation or even the monitoring of the arterial tension at least 30
      days. If the values exceed the normal, complex investigations will be made in
      order to determine the specific cause of the AHT.

PMID- 18717280
TI  - [Clinico-histopathological correlations of venous wall modifications in chronic
      venous insufficiency].
AB  - The interest manifested for the conjunctive tissue pathology leaded to the study
      of the structural disorder that appears in the varicose veins walls. The study is
      a prospective one initiated in March 2007 made on 11 patients with varicose
      disease hospitalized at Cluj-Napoca within Surgery Clinic no. II. The purpose of
      this study is to point out the histopathological modifications in the varicose
      venous wall (great saphenous vein cross, communicating veins, perforating veins),
      as well as the correlation of histopathological results with the evolutive stage
      of chronic vein insufficiency (CEAP classification) and with the clinical score
      at these patients. The histopathological (HP) results for 2 of the patients
      revealed hypertrophy of the media, intimal hyperplasia (stage II) corresponding
      to a CEAP 3. Six patients were integrated in HP stage III due to the partial
      intimal fibrosis corresponding to a CEAP 6 for one case, CEAP 4 one case, CEAP 3
      four cases. One patient had HP stage I with CEAP 3 and two patients had HP stage
      IV corresponding to CEAP 5, respectively CEAP 6.

PMID- 18717281
TI  - [Experimental left orthotopic mono-pulmonary transplantation swine model].
AB  - The swine model is an orthotopic pulmonary transplantation model often uses in
      the transplantation experiments. The purpose of this study is to control the
      transplantation technique on swine model and perform the learning curve of this
      procedure, as much from surgical than anaesthetic point of view. METHODS: 20
      orthotopic left pulmonary transplantations were performed on 20 pairs of domestic
      female pigs, weighting 30-35 kg. Tracheal intubation's time, monitoring time,
      bronchial, arterial and venous anastomosis time, warm ischemia time, were
      recorded. The causes of morbidity and mortality were also analyzed. RESULTS:
      Bronchial anastomosis was a running mattress suture. All bronchial anastomoses
      were airtight. Arterial anastomosis was a running mattress end-to-end
      anastomosis. The venous return was carried out by a left atrium-venous running
      mattress suture anastomosis. Satisfied blood flows in all arterial and venous
      anastomoses were obtained. CONCLUSIONS: We established an experimental swine
      model of pulmonary transplantation. The anaesthetic and surgical team performed
      their learning curve. Various anastomoses times and consequently, the total time
      of the intervention, were shortened.

PMID- 18717282
TI  - [Post-surgical eventrations; surgical alloplastic procedure, with supra
      aponeurosis fixation].

PMID- 18717283
TI  - [Colectomy for sigmoid colon volvulus. 1941].

PMID- 18717284
TI  - Neck nodal metastases from unknown primary: case series.
AB  - BACKGROUND: Neck nodal metastases from occult primary constitute about 5%-10% of
      all hosts harboring carcinoma of unknown primary site. Metastases in the upper
      and middle neck (levels I-II-III-IV-V) are generally attributed to head and neck
      cancers, whereas the lower neck (level IV) involvement is often associated with
      primaries below the clavicles. Diagnostic procedures include a careful clinical
      evaluation and a fiberoptic endoscopic examination of the head and neck mucosa,
      biopsies from all suspicious sites or blindly from the sites of possible origin
      of the primary, computerized tomography (CT) scan, and magnetic resonance
      radiology (MRI). The most frequent histological finding is squamous cell
      carcinoma, particularly when the upper neck is involved. SETTINGS: We report
      three cases of patients presented with nodal metastases of the neck from unknown
      primary site and we also describe the diagnostic and therapeutic approach
      employed in each one. RESULTS: One patient harbored a neuroendocrine metastatic
      deposit, the second patient a poorly differentiated carcinoma and the third one a
      malignant melanoma. CONCLUSIONS: Diagnostic procedures should be aimed at
      clarifying the histology of the nodal metastases and detecting the primary tumor
      site.

PMID- 18717285
TI  - [Nonocclusive acute mesenteric ischemia].
AB  - The authors present one case of acute mesenteric ischemia appeared to the patient
      70 years old, with HTA and coronary heart disease with heart arrhythmia treated
      with angiotensin-converting-enzyme inhibitor, anti arrhythmia agents and
      antithrombin therapy (trombostop). Acute mesenteric ischemia is not an isolated
      clinical entity, but a complex of diseases, including acute mesenteric arterial
      embolus and thrombus, mesenteric venous thrombus and nonocclusive mesenteric
      ischemia. These diseases have common clinical features caused by impaired blood
      perfusion of the intestine, bacterial translocation and systemic inflammatory
      response syndrome. Reperfusion injury is another important feature of
      nonocclusive mesenteric ischemia. We discuss about the nonocclusive mesenteric
      ischemia is the most lethal form of acute mesenteric ischemia because of the poor
      understanding of its pathophysiology and its nonspecific symptoms, which often
      delay its diagnosis. Although acute mesenteric ischemia is still lethal and in
      hospital mortality rates have remained high over the last few decades,
      accumulated knowledge on this condition is expected to improve its prognosis.

PMID- 18717286
TI  - [Left paraduodenal hernia with particular evolution].
AB  - Paraduodenal hernia is a rare situation, less than 400 cases being published in
      literature. This condition is difficult to explore, diagnose appear within an
      occlusive syndrome. The etiopathology involves perturbation of intestinal
      rotation during the intrauterine life, producing paraduodenal fossa, which
      generates conditions for internal hernias and occlusive situations. We present
      the case of a 36 years old woman with chronic epigastric pain, diagnosed as
      duodenal ulcer, later as acute pancreatitis and in the end as high occlusion
      syndrome. Open laparotomy was performed, uncovering a strangulated left
      paraduodenal hernia, with severe pathologic lesions of the intestinal loops.
      Kelotomy and pure-string suture of parietal defect was performed. Post-operative
      evolution has been difficult with hepatic failure with coagulopathy and diffuse
      intestinal hemorrhage, threatening the patient's life. Intensive care lead
      eventually to a favorable condition. The rarity of this disease, difficulty of
      diagnosis and the particular evolution were the reasons to present this rare
      case.

PMID- 18717287
TI  - Intraperitoneal cerebrospinal fluid pseudocyst. A rare complication of
      ventriculoperitoneal shunt.
AB  - The abdominal intraperitoneal cerebrospinal fluid pseudocyst is a rare but
      important complication in patients with ventriculoperitoneal shunts. We report a
      case of a 31-year-old female, in which a large abdominal pseudocyst was developed
      1 year after insertion of a ventriculoperitoneal shunt for hydrocephalus. The
      abdominal CT scan and the ultrasonographical evaluation of the abdomen showed a
      well defined, cystic mass lesion with a volume of 50 cm3, in the recessus hepato
      renal. The peritoneal tip of the shunt was located within the mass lesion. A
      distal externalization of the peritoneal catheter without excision of the
      pseudocyst was performed. Cerebrospinal fluid culture demonstrated a
      Staphylococcus epidermis infection and adequate antibiotic treatment was
      administrated. The previous symptoms improved 4 weeks later and a new catheter
      was placed intraperitoneally in a different quadrant. The postoperative course
      was uneventful. We suggest that chronic inflammation or subclinical peritonitis
      is a predisposing factor for this complication.

PMID- 18717288
TI  - Gallbladder adenoma with focal adenocarcinoma.
AB  - The majority of polypoid lesions of the gallbladder are cholesterolosis
      pseudopolyps. True neoplastic GB polyps are represented mainly by adenomas. The
      case of a 52-year old male patient with an adenomatous polyp of the GB with focal
      adenocarcinoma is presented.

PMID- 18717289
TI  - [Demetrius Cantemir in the history of surgery: the first account of
      transabdominal approach to repair groin hernias].
AB  - The first description of the transabdominal approach for hernia repair was
      written by Demetrius Cantemir, Prince of Moldavia and encyclopedic scholar, in
      his 1716 Latin manuscript "Incrementa et Decrementa Aulae Othmanicae". This
      manuscript was one of the most important of Eastern Europe at the time. It was
      first translated in English in 1734, and all subsequent translations into various
      other languages were based on this English version. The original manuscript now
      belongs to the Houghton Library of Harvard University, where it was recently
      rediscovered in 1984 by V. Candea. D. Slusanschi has made the first Romanian
      translation of the first two volumes based on the original latin manuscript. This
      translation is now in press. Our article presents for the first time a fragment
      of this Romanian translation from the Annotations of Volume two, chapter four. In
      this fragment, Demetrius Cantemir describes the surgical procedure practiced by
      Albanian physicians in the prince's palace in Constantinopol. The patient was the
      secretary of the prince. There is a detailed description of the postsurgical
      therapy and the medical course to recovery. It was first partially reproduced by
      Mercy in his book on hernia published in 1892, and more recently by Meade in
      1965. We consider useful to present to the medical community this valuable but
      less known contribution to the history of medicine.

PMID- 18717290
TI  - The war on drugs and addiction.

PMID- 18717291
TI  - Bioidentical hormones: panacea for menopausal hormonal therapy or bio-beware?

PMID- 18717292
TI  - Implementation of an insulin protocol using a multiplier-based calculation for
      determining infusion rates in critically ill patients.
AB  - Evaluation of a nurse-titrated insulin infusion method for hyperglycemia
      treatment was conducted on data from a 19-bed mixed medical-surgical intensive
      care unit (ICU) with results demonstrating that glucose management did not
      consistently meet target glucose goals. A multidisciplinary team was created to
      evaluate and implement a method of insulin infusion administration that would
      decrease titration subjectivity and improve glycemic management. Utilizing a Plan
      Do-Study-Act (PDSA) cycle for trial implementation of a calculation-based method,
      data demonstrated a significant improvement in glycemic management when compared
      to the previous method of insulin administration.

PMID- 18717293
TI  - Typhoid fever in a young immigrant child: a case report and review of the
      literature.
AB  - Typhoid fever is a systemic disease not endemic to South Dakota. We report a case
      of a young child, living in South Dakota since immigrating with his family as a
      refugee, who developed typhoid fever. Contact investigation failed to identify a
      source, suggesting that the infection was acquired abroad. The clinical
      presentation of typhoid is discussed, and the literature relevant to diagnosis,
      treatment and prevention is reviewed.

PMID- 18717294
TI  - Doripenem: a new carbapenem.

PMID- 18717295
TI  - Duck-style exercise.

PMID- 18717296
TI  - Hospital outpatient quality data reporting program.

PMID- 18717297
TI  - The pregnant health care worker--an evidence-based approach to job assignment and
      reassignment.
AB  - Women of childbearing age must carefully consider the risks and benefits of
      working in the field of health care prior to becoming pregnant.

PMID- 18717298
TI  - Caring for our wounded warriors.

PMID- 18717299
TI  - Reflections on the culture of veterans.
AB  - Veterans, as a cultural group, present unique challenges to health care
      providers. Veteran culture includes health inequalities and health disparities
      related to posttraumatic stress disorder, depression, and substance abuse that
      must be understood in context to provide the best care possible to this
      population. Veterans are not, however, frequently viewed in terms of culturally
      competent nursing care. Changes in the approach to this population are necessary
      to provide effective, comprehensive, and compassionate care.

PMID- 18717300
TI  - Transition from the Afghanistan and Iraqi battlefields to home: an overview of
      selected war wounds and the federal agencies assisting soldiers regain their
      health.
AB  - Occupational health nurses are encountering veterans in the workplace who have
      served one or more tours of duty in Afghanistan or Iraq. Soldiers making the
      transition from combat to civilian life may have physical and mental injuries
      from war. Occupational health nurses who recognize the unique nature of these
      injuries and are knowledgeable about resources for meeting veterans' needs will
      be instrumental in facilitating their return to civilian life.

PMID- 18717301
TI  - In the line of fire: traumatic brain injury among Iraq War veterans.
AB  - Soldiers returning home from Iraq are experiencing an increased number of head
      injuries related to blasts and explosions compared to soldiers of previous
      conflicts. These injuries are often undetected until the soldiers return home and
      have difficulty functioning as they did prior to the war. It is therefore
      important for occupational health nurses to understand blast injury, its
      pathophysiology, methods for detecting traumatic brain injury, and how these
      soldiers can be treated.

PMID- 18717302
TI  - Mindfulness meditation for veterans---implications for occupational health
      providers.
AB  - Mindfulness meditation (MfM) is a mind-body therapy identified by the National
      Center for Complementary and Alternative Medicine. Initially taught in a formal
      classroom setting, MfM is a sustainable intervention with minimal costs that can
      be used over time. For veterans, after mastery, this technique shows promise in
      improving health outcomes and quality of life. This article describes MfM,
      discusses the conceptual framework and evidence-based research for MfM, and
      identifies the implications of MfM use by health care providers who are caring
      for war veterans.

PMID- 18717303
TI  - The returning veteran--a lesson in reintegration.
AB  - Families, coworkers, employers, and health care providers play a role in the
      reintegration of returning veterans.

PMID- 18717304
TI  - [It is necessary to set up standards for diagnosis and treatment of auditory
      neuropathy].

PMID- 18717306
TI  - [Expert forum on auditory neuropathy].

PMID- 18717305
TI  - [Auditory neuropathy and inner hair cell and synapses].

PMID- 18717307
TI  - [Audiological characteristics and localization of lesions in children with
      retrocochlear auditory nerve impairment].
AB  - OBJECTIVE: To explore the clinic characteristics, audiological characteristics
      and location of lesions in children with retrocochlear auditory nerve impairment
      which, including auditory neuropathy characterized by severely abnormal results
      of ABR and normal results of DPOAE. METHODS: Between 2002 and 2006, eighty-six
      cases (165 ears) with severely abnormal ABR but normal results of DPOAE were
      enrolled in the study group. The mean patient age was one year and one-month-old,
      with a range of 8 days to 7 years. The cases with abnormal conductive function
      were excluded. The cases with severely abnormal ABR and normal cochlear functions
      as measured by DPOAE and without abnormal conductive function were selected as
      the cochlear lesion group. Some same age healthy children without hearing loss
      were subjected as normal control group. The latency and amplitude of waves I, III
      and V, the inter peak latency I-III was compared among the three group. RESULTS:
      (1) Fifty-one cases (59.3%) had a history of hypercholesterolemia during neonatal
      period, but 40 cases (46.51%) had a severe hypercholesterolemia and 11 cases
      (12.79%) had mild or moderate hypercholesterolemia. Clinical features common
      among the population included a history of dyskinesia [n = 40 (46.51%)], hearing
      and language disorder [n = 10 (11. 63%)]. Thirty-two cases (37.2%) were
      accompanied by cerebral palsy . (2) Among the 165 ears, absent ABRs to click
      stimuli presented at 103 dB was in 103 ears, only wave I was developed in 27 ears
      and only wave V was developed in 19 ears,wave I and III in 13 ears and
      differentiated wave I and V in 3 ears. (3) When compared to control group, the
      latency of wave I was prolonged and amplitude of wave I was lower in cases with
      only wave I developed (t = -6.75 and 2.58, P < 0.05). For for cases with only
      wave I and III differentiated, the latency and amplitude of wave I was the same
      but the latency of wave III was prolonged and amplitude of wave III was lower
      while interpeak latency I-III was prolonged. CONCLUSIONS: Auditory neuropathy
      which was characterized by severely abnormal ABR was the most common type of
      retrocochlear auditory nerve impairment. It was mainly due to a disorder of VIII
      nerve. The pathologies that affect higher levels of the auditory pathway, from
      the brainstem to the auditory cortex, might be the main sites of lesion in cases
      with only wave I developed. Superior olivary nucleus where wave III was generated
      and higher levels of the auditory pathway might be the main sites of lesion in
      cases with wave I and III differentiated. The low-amplitude wave V was not
      characteristics of auditory neuropathy. Cerebral cortex, brain stem auditory
      nucleus and VIII nerve might be damaged successively in cases with retrocochlear
      auditory nerve impairment induced by hypercholesterolemia.

PMID- 18717308
TI  - [Correlation between phonetically balanced maximum and pure tone auditory
      threshold among 106 auditory neuropathy patients].
AB  - OBJECTIVE: To estimate correlation between phonetically balanced maximum (PB max)
      and pure tone auditory threshold in auditory neuropathy (AN) patients. METHODS:
      One hundred and six AN patients were identified using multiple criteria including
      PB max, a metric for speech recognition, pure tone auditory threshold, acoustic
      emission test, distortion products otoacoustic emission (DPOAE) and auditory
      brainstem response (ABR). SPSS statistical software was used to estimate the
      Pearson's correlation between PB max and pure tone auditory threshold and to test
      whether pure tone auditory threshold, or auditory configuration had a significant
      impact on PB max. RESULTS: Even the patients had the same or similar values for
      pure tone auditory threshold or auditory configuration, varied values of PB max
      were found in two hundreds and twelve ears for 106 patients. Analysis of the data
      for 106 patients revealed a negative correlation (r = -0. 602, P <0. 01) between
      PB max and pure tone auditory threshold, i. e. hearing loss at a mild relates to
      a lower PB max. By using analysis of variance (ANOVA) method, it was found that
      both pure tone auditory threshold and auditory configuration had a significant (P
      <0.01) impact on the patients' PB max. CONCLUSIONS: This analysis implicated the
      promise and potential of pure tone auditory threshold and auditory configuration
      for predicting PB max of the AN patients, and improving the diagnosis of AN.

PMID- 18717309
TI  - [Electrophysiological findings for 106 cases with auditory neuropathy].
AB  - OBJECTIVE: To analyses the clinical characteristics and electrophysiological
      finding of 106 patients with auditory neuropathy (AN). Investigate the
      differential curve type of pure tone audiogram and the abnormal ABR. METHODS:
      Review the history of patients, pure tone audiometry, middle ear acoustic
      reflexes, auditory brainstem response, distortion product otoacoustic emission
      and radiologic imaging studies of the brain of 106 patients with AN during
      December 2001 to May 2007 in retrospect. RESULTS: The 106 patients with AN were
      of both genders. The age were between 11-37 years old, and the average age was
      17.5 years old. The most patients were adolescence (70.8%). Twelve cases of the
      106 patients had evidence of other peripheral neuropathy in addition to hearing
      loss. Another 94 patients were idiopathic origins. The pure tone audiogram showed
      a minimal to moderate sensorineural hearing loss at low frequencies 0.5 kHz and
      0.25 kHz in 209 ears (98.6%). The average hearing threshold (WHO 1997) in 23.2%
      of disordered ears at less than 25 dB in the "normal" range. Auditory brainstem
      response could not be recorded in 124 ears (58.5%) at maximum stimulus. The other
      88 ears showed 1 or 2 wave, but the wave were small. There were 23 patients which
      one side ear ABR was 1 or 2 small waves presented, but the contralateral side
      were all waves absent. In 3 cases of AN with other peripheral neuropathy which
      ABR were both ears 1 or 2 small wave ear recorded. However, 1 patient in our
      sample could not be detected distortion product otoacoustic emission at 3-6 kHz
      (left ear) and 5-6 kHz (right ear). CONCLUSIONS: AN was not rare in adolescence.
      The average hearing threshold for AN should be discussed.

PMID- 18717310
TI  - [Analysis of the character of self-adaptation of nasal structure in patients with
      nasal septum deviation].
AB  - OBJECTIVE: To analyze the different characters of nasal airflow-field between 10
      patients with nasal septum deviation and 20 healthy Chinese people by the method
      of three-dimensional reconstruction of these people's nasal cavity and numerical
      simulation of the flow field in these nasal cavity models. The character of
      airflow-field was considered by analyzing the relationship between the structure
      and function of the human nose. METHODS: Based on the data obtained from the CT
      images, 10 patients with nasal septum deviation and 20 healthy Chinese people's
      nasal cavity models were reconstructed by the method of surface rendering. The
      flow field in these three-dimensional models was simulated with finite element
      method. The different characters of nasal airflow-field was analysed between two
      groups of people. RESULTS: The airflow distribution in the nasal cavity model
      could be acquired from the simulation results of the velocity. The airflow for
      patients with nasal septum deviation mainly passed through the broad nasal
      cavity, especially in the middle part of meatus of nose. In the healthy people
      group, the airflow mainly passed through the main side of the nasal cavity,
      especially in the middle and inferior part of the meatus of nose. The pressure
      value at any point in the nasal cavity model could be obtained from the results
      of the pressure plot. In the patients with nasal septum deviation, the pressure
      mainly dropped in the part of the nasal septum deviation, accounting
      approximately 71.36% of the total pressure drop. In the group of healthy people,
      the pressure dropped mainly in the limen nasi, accounting approximately 58.78% of
      the total pressure drop. The nasal airway resistance of the patients with nasal
      septum deviation was larger than that in the group of healthy people.
      CONCLUSIONS: The three-dimensional nasal airway can reflect the characters of the
      human nasal airway. It can be used to analyze the change of the aerodynamic in
      nasal cavity caused by the abnormal anatomy of the nose. This experiment can
      proof that human nose has the function of self-adaptation, it can build a
      foundation for the construction of the model of self-adaptation of the human
      nose.

PMID- 18717311
TI  - [Primary study on glycan structure in pathopoiesis mechanism of recurrent
      respiratory papillomatosis].
AB  - OBJECTIVE: To compare the molecular basis difference between recurrent
      respiratory papillomatosis (RRP) and vocal cord polyp, to analyze the expression
      of glycan structural genes, and to discuss the pathopoiesis mechanism of RRP.
      METHODS: The gene expressing profile between the 3 groups papilloma and the vocal
      cord polyp regarded as normal larynx epithelium were compared using mRNA parallel
      amplify and the human genome gene expressing microarray. Through cluster
      analysis, Gene Ontology function gene annotation and path way analysis, the
      relative gene of RRP and HPV infection were acquired. RESULTS: According to three
      microarrays results, total 567 expression changed genes related to HPV induce RRP
      were acquired. A serial change of glycan structure biosynthesis and degradation
      pathways was significant. The expression of dolichyl-phosphate
      mannosyltransferase polypeptide 1 (DPM1), asparagine-linked glycosylation 1
      homolog (ALG1), fucosyltransferase 8 (FUT8) and alpha-mannosidase 1A (MAN1A) were
      regulated and beta-hexosaminidase (HEXB), beta1-galactosidase (GLB1), exostoses 1
      (EXT1), fucosyltransferase (FUT) reduced expression and heparan sulfate 3-O
      sulfotransferase 1 (HS3ST3A1) increased expression. The two related enzymes of
      the glycosphingolipids which is the main composed of the cell membrane, beta-3-N
      acetylglucosaminyltransferase 4 (B3GNT4) and UDP-glucose ceramide
      glucosyltransferase (UGCG) increase expression, HEXB and GLB1 reduced expression.
      CONCLUSIONS: The alteration of the coding genes of glycan structure biosynthesis
      and degradation pathways were significantly and characteristically in
      pathopoiesis mechanism of RRP. This abnormality may be the beginning of tumor
      form HPV infection.

PMID- 18717312
TI  - [Overexpression of Hath1 induces production of hair cell-like cells in greater
      epithelial ridge cell cultures from postnatal rat cochlea].
AB  - OBJECTIVE: To investigate the effect of Hath1 (human atonal homolog 1)
      overexpression on greater epithelial ridge (GER) cells from postnatal rat cochlea
      in vitro. METHODS: GER cells were isolated by using a combinatorial approach of
      enzymatic digestion and mechanical separation from P1 rat cochlear. The GER cell
      cultures were infected by adenovirus containing Hath1 and enhanced green
      fluorescent protein (ad-Hath1-EGFP), while transfecting EGFP(ad-EGFP) was as
      controls. Immunostaining were performed at different time points after adenovirus
      infection. RESULTS: Some of the infected GER cells became myosin VIIa-positive
      following ad-Hath1-EGFP infection. The earliest time point to see induction of
      hair cell differentiation (hair cell marker expression) by ad-Hathl was 5 days
      post-infection. In contrast, infection of the GER sheet cultures with ad-EGFP
      control virus did not show any myosin VIIa-positive cells at 3-12 days post
      infection in all cultures examined. CONCLUSIONS: GER cells may potentially serve
      as hair cell progenitors and they are capable of differentiating hair cell-like
      cells when forced to express Hath1.

PMID- 18717313
TI  - [Effect of sodium salicylate on the auditory brain stem response threshold and
      expression of glutamic acid decarboxylase in spiral ganglion of juvenile and
      adult guinea pigs].
AB  - OBJECTIVE: To study the differences of regulation of sodium salicylate on the
      auditory brain stem response (ABR) threshold and expression of glutamic acid
      decarboxylase (GAD) protein in spiral ganglion of juvenile and adult guinea pigs.
      METHODS: Fourty juvenile guinea pigs which were born just four days and fourty
      adult guinea pigs which were born thirty days were selected. They were divided
      four groups (group A; group B; group C; group D). ABR threshold was detected
      before administration, after administration for 15 days and after administration
      stopped for 30 days. The protein expression of GAD were measured after
      administration for 15 days and after administration stopped for 30 days by the
      method of immunohistochemistry. RESULTS: ABR threshold of juvenile sodium
      salicylate groups (group C) was increased remarkably than that of before
      administration and the control after administration for 15 days (P < 0.001). ABR
      threshold of group C was returned to the level of that of before administration
      and after administration stopped for 30 days. ABR threshold of adult sodium
      salicylate groups (group D) was increased remarkably than that of before
      administration and the control after administration for 15 days (P < 0.001). ABR
      threshold of group D was kept the high level after administration stopped for 30
      days. The protein expression of GAD of sodium salicylate groups (group C and D)
      was decreased than that of the control after administration for 15 days. The
      protein expression of group C was more visible regression than that of group D (t
      = 4.7, P < 0.001). The protein expression of group C was returned the level of
      before administration after administration stopped for 30 days, but the protein
      expression of group D was kept the high level. CONCLUSIONS: The results suggest
      that sodium salicylate can regulate differently ABR threshold and expression of
      GAD protein in spiral ganglion of juvenile and adult guinea pigs. The effects of
      sodium salicylate on ABR threshold and expression of GAD protein in spiral
      ganglion of juvenile pigs are more noticeable than that of adult guinea pigs, but
      these changes are easier to return the normal than that of adult guinea pigs.

PMID- 18717314
TI  - [Myxoid chondrosarcoma of nasal cavity and septum: a case report].

PMID- 18717315
TI  - [Transoral endoscopic CO2 laser surgery for hypopharynx in experimental animals].
AB  - OBJECTIVE: To explore the substantial resection limits of CO2 laser surgery for
      hypopharynx and the course of wound healing in animals, for the purpose of
      evaluating the clinic usefulness of transoral CO2 laser surgery in the treatment
      of selected hypopharyngeal carcinomas. METHODS: Twenty-three dogs were randomly
      assigned to two groups. Group one (11 dogs) received left piriform sinus
      resection, group two (12 dogs) received the resection of posterior wall of the
      hypopharynx. Six dogs in group one were killed immediately or 4, 8, 12, 16, 20 d
      post-operatively. Seven dogs in group two were killed immediately or 7, 14, 21,
      28, 35, 42 d post-operatively. The whole larynx and hypopharynx were taken out
      and the specimens were examined by naked eyes and under microscope. The other 5
      dogs in each group were fed until the wound healed, the duration were observed.
      RESULTS: All the operations were successful and the results were satisfactory. In
      group one, the dogs could take food the day after operation; two dogs had slight
      cough during eating and recovered after five days. In group two, the dogs could
      take food the next day after operation, eight dogs had slight cough during eating
      and recovered after ten days. The excision dimension was satisfactory. In group
      one (resection of the lateral wall of piriform sinus), the size of raw surface
      was (7.5 +/- 0.8) cm2 (x +/- s) and the healing time was (18.4 +/- 1.5) d. In
      group two (resection of the posterior wall of the hypopharynx), the wound surface
      was (7.0 +/- 0.5) cm2 and the healing time was (39.8 +/- 1.9) d. The healing time
      in group two was significantly longer than that in group one (t = 19.535, P <0.
      01). The post-operative healing process were observed, including cellulose
      membrane coverage, granulation filling and epithelization. CONCLUSIONS: Transoral
      CO2 laser was suitable for partial hypopharynx resection. Animals can recuperate
      well with little complications. Although the course of wound healing was delayed,
      wound surface can recover with good laryngeal and deglutition functions.

PMID- 18717317
TI  - [A citation analysis of Chinese Journal of Otorhinolaryngology Head and Neck
      Surgery quoted by doctoral dissertations].

PMID- 18717316
TI  - [Effect of RNA interference mediated gene silencing of DJ-1 on proliferation of
      laryngeal carcinoma cell line Hep-2].
AB  - OBJECTIVE: To assess the effect of small interfering RNA (siRNA)-mediated gene
      silencing of DJ-1 on the proliferation of human laryngeal carcinoma cell line Hep
      2. METHODS: Three siRNA sequences specific to DJ-1 gene were synthesized
      according to GenBank. Human laryngeal carcinoma cell line Hep-2 was cultured and
      divided into 4 groups: non-specific group (siRNA control) and 3 RNAi groups,
      transfected with specific DJ-1 siRNA (siRNA1, siRNA2, siRNA3). The mRNA and
      protein levels of DJ-1 were detected by reverse transcription-polymerase chain
      reaction (RT-PCR) and Western Blot respectively. Cell apoptosis were analyzed by
      flow cytometry. The proliferation of Hep-2 cells was assessed by MTT assay.
      RESULTS: DJ-1 siRNA down-regulated the mRNA and protein levels of DJ-1 in Hep-2
      cells. After transfection, the expression of DJ-1 mRNA and protein levels in Hep
      2 cells of the DJ-1 siRNA1 group were significantly lower than those of non
      specific siRNA control group. MTT assay showed that DJ-1 siRNA1 group inhibited
      proliferation of Hep-2 cells. Flow cytometry showed that apoptosis rate of the DJ
      1 siRNA1 group (15.7%) was significantly higher than that of non-specific siRNA
      control group (4.5%) or untransfected group (3.5%), t = 4.736, P < 0.01.
      CONCLUSIONS: Specific siRNA targeting DJ-1 can effectively inhibit DJ-1
      expression, resulting in the reduced proliferation and the enhanced apoptosis in
      Hep-2 cells.

PMID- 18717318
TI  - [Effect of total thyroidectomy on growth and development of children and
      adolescents].

PMID- 18717319
TI  - [Surgical management of recurrent thyroglossal cyst and fistula].

PMID- 18717320
TI  - [Primary extranodal non-Hodgkin's lymphoma of the external auditory canal and
      tympanum: a case report].

PMID- 18717321
TI  - [Pharmacological intervention for contact granuloma of the larynx].

PMID- 18717322
TI  - [A case with malignant ameloblastoma of larynx].

PMID- 18717323
TI  - [Ribbon synapse of inner hair cell].

PMID- 18717324
TI  - [An ethylmalonic-aciduria patient with auditory neuropathy].

PMID- 18717325
TI  - [Audiological evaluation and etiologic research on auditory neuropathy].

PMID- 18717326
TI  - [A speech given by a Canadian member of the 8th editorial board of Chinese
      Journal of Otorhinolaryngology Head and Neck Surgery on its 2nd conference].

PMID- 18717327
TI  - [Advance of several types of important marine antitumor drugs].
AB  - Marine antitumor drugs have been the research focus in the world. Recently,
      advancement has been made in the investigation of six types of compounds
      including bryostatin-1, ecteinascidin-743, dolastatin, didemnin B, psammaplin and
      halichondrin B. In this review, we summarized the recent research progress of the
      above mentioned marine antitumor drugs and their derivatives. Also, the
      development tendency of marine antitumor drugs was discussed.

PMID- 18717328
TI  - [Advances in new technique pseudophase biochromatography].
AB  - The current status and latest advances in new technique pseudophase
      biochromatography are reviewed. After brief introduction to the principle of new
      technique pseudophase biochromatography, the nature and various influence factors
      including the compositions, the types of new technique pseudophase
      biochromatography system are summarized in detail and the aspects of the future
      applications biochromatography in life science are described.

PMID- 18717329
TI  - [Advances in the study of lipid-based cubic liquid crystalline nanoparticles as
      drug delivery system].
AB  - Various geometric shapes and structures self-assembled of amphiphilic lipids when
      present in an aqueous environment, as active delivery vehicles, are becoming one
      of focuses of drug delivery system. Lipid-based cubic liquid crystalline
      nanoparticles (or Cubosomes) consisting of "honeycombed (cavernous)" structure
      spontaneously formed when a certain concentration of amphiphilic lipids dispersed
      in aqueous solution has curved bicontinuous lipid bilayer in three dimensions,
      separating two congruent networks of water channels. Its unique structure
      consists of internal double water channels and large interfacial areas, which
      reveal great flexibility in encapsulation efficiency of various polarities and
      amount of drugs, and has variegated range of drugs encapsulated. As a drug
      delivery vehicle, high drug payloads, stabilization of peptides or proteins and
      simple preparation process are also its advantages. The ability of cubic phase to
      incorporate and control release of drugs of varying size and polar
      characteristics, and biodegradability of lipids make it an interesting drug
      delivery system for various routes of administration, including oral, topical (or
      mucosal) and intravenous administrations, with extensive application in a
      multitude of dosage forms. Furthermore, a number of different proteins in cubic
      phase appear to retain their native conformation and bioactivity, and are
      protected against chemical and physical inactivation. In this paper,
      investigations of lipid-based cubic liquid crystalline nanoparticles are reviewed
      and summarized, with a hope to provide a reference for its in-depth study. At the
      end, the authors made a development prospect of this novel excellent candidate
      for active ingredients delivery vehicle.

PMID- 18717330
TI  - [Anti-HIV activities of HIV-1 reverse transcriptase inhibitor racemic 11-demethyl
      calanolide A].
AB  - To compare the anti-HIV-1 activities of (+/-)-11-demethyl-calanolide A and its
      mother compound (+/-)-calanolide A in vitro and in vivo, the inhibitory
      activities of the two compounds on HIV-1 reverse transcriptase (RT) were detected
      in vitro with isotope 3H assay. The cytotoxicity and inhibition of cytopathic
      effect (CPE) were studied in HIV-1 IIIB infected MT-4 cell cultures by MTT
      staining method; Mice were given with the two compounds 100 mg x kg(-1) once
      intraperitoneally, then the mouse sera taken on 30 min and 60 min after
      administration were detected for the inhibition of HIV-1 RT in vitro. The data
      showed that (+/-)-11-demethyl-calanolide A and (+/-)-calanolide A inhibited HIV-1
      RT in vitro with 50% inhibitory concentration (IC50) of (3.028 +/- 2.514)
      micromol x L(-1) and (3.965 +/- 5.235) micromol x L(-1), and also inhibited CPE
      in HIV-1 IIIB infected MT-4 cell cultures with IC50 of (1.081 +/- 0.337) micromol
      x L(-1) and (1.297 +/- 0.076) micromol x L(-1), respectively. After
      intraperitoneal injection of 100 mg x kg(-1) of the two compounds in mice, all
      the mice sera taken 30 and 60 min afterward inhibited HIV-1 RT in vitro. In
      comparison with control mice sera, the inhibitory rates of the sera for (+/-)-11 
      demethyl-calanolide A were (42.7 +/- 1.5)% at 30 min (P < 0.01) and (32.2 +/-
      6.1)% at 60 min (P < 0.05), separately, while the inhibitory rates of the sera
      for (+/-)-calanolide A were (40.7 +/- 6.3)% at 30 min (P < 0.01) and (29.2 +/-
      6.7)% at 60 min. The results suggested that (+/-)-11-demethyl-calanolide A is a
      new non-nucleoside HIV-1 RT inhibitor, its anti-HIV-1 activities in vitro, in
      cell cultures and in mice were slightly higher than that of its mother compound
      (+/-)-calanolide A and warrants further studies.

PMID- 18717331
TI  - Reversal effect of isotetrandrine, an isoquinoline alkaloid extracted from Caulis
      Mahoniae, on P-glycoprotein-mediated doxorubicin-resistance in human breast
      cancer (MCF-7/DOX) cells.
AB  - This study investigated the reversal effect of isotetrandrine, an isoquinoline
      alkaloid extracted from Caulis mahoniae, on P-glycoprotein-mediated multidrug
      resistance in human breast cancer doxorubicin-resistant (MCF-7/DOX) cells. RT-PCR
      assay and immunity histochemistry assay were used to determine the expression
      level of mdrl gene and P-gp in MCF-7/DOX cells to elucidate resistant character
      of MCF-7/DOX cells. The activity of isotetrandine to enhance doxorubicin
      cytotoxicity was tested using MTT (3-(4, 5-dimethyhthiazol)-2,5 
      diphenyltetrazolium bromide) assay and was evaluated by the reversal fold (RF)
      values. Intracellular accumulation of doxorubicin was assessed by the
      determination of doxorubicin-associated fluorescence intensity. Effect of
      isotetrandrine on the expression level of P-gp in MCF-7/DOX cells was then
      determined by immunity histochemistry assay. The ability of isotetrandrine to
      inhibit P-gp function was evaluated by detecting the accumulation and efflux of
      rhodamine 123 (Rh123) with flow cytometry (FCM). Verapamil was employed as a
      comparative agent in whole experiment. The results indicated that MCF-7/DOX cells
      had phenotype of MDR and that the positive expression of P-gp was their resistant
      character. 10 microg x mL(-1) isotetrandrine could distinctly enhance
      cytotoxicity of DOX in MCF-7/DOX cells and reversal fold (RF) was significantly
      higher than that of verapamil (P < 0.05), but it hardly affected cytotoxicity of
      DOX in MCF-7 cells and the expression level of P-gp in MCF-7/DOX cells. The
      ability of isotetrandrine to inhibit P-gp function was reversible, because
      incubation of MCF-7/DOX cells with isotetrandrine caused a marked increase in
      uptake and a notable decrease in efflux of Rh123 and a marked increase of
      intracellular DOX concentrations. In conclusion, isotetrandrine exhibited potent
      effect on the reversal of P-gp-mediated MDR in vitro, suggesting that it might
      become a candidate of effective MDR reversing agent in cancer chemotherapy.

PMID- 18717332
TI  - [5-HT1A/1B receptors, alpha2-adrenoceptors and the post-receptor adenylate
      cyclase activation in the mice brain are involved in the antidepressant-like
      action of agmatine].
AB  - This study is to explore the possible mechanisms of the antidepressant-like
      effect of agmatine. By using two traditional "behavior despair" model, tail
      suspension test and forced swimming test, we examined the effects of some
      monoamine receptor antagonists (including beta-adrenergic receptor antagonist
      propranolol, beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist
      pindolol, alpha2-adrenergic receptor antagonists yohimbine and idazoxan and 5-HT3
      receptor antagonist tropisetron) on the antidepressant-like action of agmatine in
      mice. Activity of adenylate cyclase (AC) in the synapse membrane from rat frontal
      cortex was determined by radioimmunoassay. Single dose of agmatine (5-40 mg x kg(
      1), ig) dose-dependently decrease the immobility time in tail suspension test in
      mice, indicating an antidepressant-like effect. The effect of agmatine (40 mg x
      kg(-1), ig) was antagonized by co-administration of beta-adrenergic receptor
      antagonist/5-HT1A/1B receptor antagonist pindolol (20 mg x kg(-1), ip), alpha2
      adrenergic receptor antagonists yohimbine (5-10 mg x kg(-1), ip) or idazoxan (4
      mg x kg(-1), ip), but not beta-adrenergic receptor antagonist propranolol (5-20
      mg x kg(-1), ip) and 5-HT3 receptor antagonist tropisetron (5-40 mg x kg(-1),
      ip). Agmatine (5-40 mg x kg(-1), ig) also dose-dependently decrease the
      immobility time in forced swimming test in mice. The effect of agmatine (40 mg x
      kg(-1), ig) was also antagonized by pindolol (20 mg x kg(-1), ip), yohimbine (5
      10 mg x kg(-1), ip), or idazoxan (4 mg x kg(-1), ip). Incubation of agmatine (0.1
      6.4 micromol x L(-1)) with the synaptic membrane extracted from rat frontal
      cortex activated the AC in a dose-dependent manner in vitro. While the effect of
      agmatine (6.4 micromol x L(-1)) was dose-dependently antagonized by pindolol (1
      micromol x L(-1)) or yohimbine (0.25-1 micromol x L(-1)). Chronic treatment with
      agmatine (10 mg x kg(-1), ig, bid, 2 w) or fluoxetine (10 mg x kg(-1), ig, bid, 2
      w) increased the basic activity, as well as the Gpp (NH)p (1-100 micromol x L(
      1)) stimulated AC activity in rat prefrontal cortex. These results indicate that
      regulation on 5-HT1A/1B and alpha2 receptors, and activation AC in the frontal
      cortex is one of the important mechanisms involving in agmatine's antidepressant
      like action.

PMID- 18717333
TI  - [Proliferation inhibition of lambda-carrageenan oligosaccharides on HUVEC and
      expression of apoptotic relevant genes].
AB  - To study the anti-proliferation effect of lambda-carrageenan oligosaccharides
      (lambda-CO) on human umbilical vein endothelial cells (HUVECs) and expression of
      apoptotic relevant genes, the influence of lambda-CO on HUVECs proliferation was
      measured by MTT assay; apoptotic rate, cell cycle distribution and the level of
      active caspase-3 of HUVECs were analyzed using flow cytometry; the mRNA level of
      apoptosis related genes was determined by RT-PCR. At a high concentration of 1 mg
      x mL(-1), lambda-CO significantly inhibited the endothelial cell proliferation.
      Annexin-V FITC/PI double stain assay showed that when treated with 0, 0.8, 1 mg x
      mL(-1) of lambda-CO for 24 h, cell apoptotic rates were (1.67 +/- 1.6)%, (11.48
      +/- 2.4)% and (13.81 +/- 2.2)%, respectively, when treated for 48 h, cell
      apoptotic rates were (2.02 +/- 2.3)%, (13.84 +/- 1.9)% and (38.72 +/- 2.5)%,
      respectively, cell cycle assay showed the decrease of cells in G0/G1 phase, and
      increase in S phase. Furthermore, we observed the level of active caspase-3
      increased in a dose-dependent manner at 24 th and 48 th. RT-PCR results indicated
      that mRNA of TNFalpha, p53, caspase-8 and caspase-3 in cells increased after
      treated with lambda-CO. lambda-CO induce apoptosis of HUVECs in a dose-dependent
      way and arrests cells at S phase, which mainly due to the up-regulation of
      apoptotic genes such as TNFalpha, p53, caspase-8, caspase-3 and increase the
      level of active caspase-3.

PMID- 18717334
TI  - [Effect of total flavonoid in leaves of Ginkgo biloba on the apoptosis of
      eosinophil in broncho alveloar lavage fluid].
AB  - This study was to investigate the effect of total flavonoid in leaves of Ginkgo
      biloba (total flavonoid in leaves of Ginkgo biloba, FG) on the apoptosis of
      eosinophils (EOS) in broncho alveloar lavage fluid (BALF) of asthma mice. Mouse
      asthma model was established by ovalbumin (OVA) challenge methods. After
      atomizing therapy for two weeks, differential count in BALF, morphological change
      and proportion of apoptosis were detected by AO/EB stain and Annexin V-FITC/PI.
      The number of total leucocytes and eosinophils in BALF decreased obviously after
      FG treatment. Compared with model group, the number and proportion of EOS
      apoptosis increased significantly after FG treatment. The results indicated that
      one of the anti-inflammation mechanisms of FG might be promoting apoptosis of
      eosinophils.

PMID- 18717335
TI  - [Hydroxysafflor yellow A up-regulates HIF-1alpha via inhibition of VHL and p53 in
      Eahy 926 cell line exposed to hypoxia].
AB  - In present study, we investigated the mechanism of regulating HIF-1alpha
      expression by hydroxysafflor yellow A (HSYA) in Eahy 926 cell line under 1% O2
      hypoxia. Eahy 926 cells were incubated with HSYA (100, 10 and 1 micromol x L(-1))
      under hypoxia for the indicated time after treatment. Cell proliferation rate was
      detected using MTT assays. VHL and p53 location and protein expression were
      analyzed by immunocytochemical stain. HIF-1alpha, VHL and p53 mRNA expression
      were detected by RT-PCR. Protein expression of HIF-1alpha, VHL and p53 were
      assayed by Western blotting method. HSYA at 100 micromol x L(-1) increased Eahy
      926 cells proliferation rate under hypoxia. HIF-1alpha mRNA and protein
      expression were up-regulated in the presence of HSYA. VHL, p53 mRNA and protein
      expression decreased significantly after 8 hours of treatment under hypoxia. HSYA
      protected Eahy 926 cells from hypoxia, and up-regulated HIF-1alpha expression
      partially via its inhibition of VHL and p53 expression.

PMID- 18717336
TI  - [Synthesis and antitumor activities of triazacyclodecane and its platinum (II)
      complex].
AB  - To search for potential antitumor drugs with potent efficiency and low toxicity,
      a novel 1,4,7-triazacyclodecane and its platinum (II) complex were synthesized.
      These compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, MS
      spectra, thermoanalysis and conductivity measurement. Antitumor activity study
      indicated these compounds had strong antitumor activity in vitro to some extent.
      Inhibition of human liver tumor of CA was examined by antitumor rate and growth
      rate, complex C showed inhibition activity on transplanting-tumor growth of CA,
      12 mg x kg(-1) was as potent as cisplatin, its ID50 was 853.6 mg x kg(-1).

PMID- 18717337
TI  - [Design, synthesis and anti-HBV activity of L-amino acid ester prodrugs of
      acyclic nucleoside phosphonates].
AB  - To design and synthesis a series of novel L-amino acid esters prodrugs of acyclic
      nucleoside phosphonates with more potent anti-HBV activity, adefovir dipivoxil
      was used as lead compound, according to the results of enhanced oral
      bioavailability and antiviral activities of nucleoside L-amino acid ester
      prodrugs. Eleven novel L-amino acid ester prodrugs of acyclic nucleoside
      phosphonates were designed and synthesized, their anti-HBV activities were
      evaluated in HepG2 2.2.15 cells. Eight compounds exhibited antiviral activity,
      and compound 11 showed the most potent anti-HBV activity and highest selective
      index in vitro (EC50 0.0952 micromol x L(-1), SI 69523). Moreover, by analyzing
      the primary structure and activity relationship of these compounds, it could be
      suggested that L-amino acid ester strategy has significant potential in the
      acyclic nucleoside phosphonates prodrug design.

PMID- 18717338
TI  - [Triterpene saponins from Adinandra nitida].
AB  - To investigate the chemical constituents of the leaves of Adinandra nitida,
      several column chromatography methods were used to isolate the chemical
      constituents of this plant. The structures were elucidated on the basis of
      spectral data. Six compounds were isolated and identified as 2alpha, 3alpha,
      19alpha-trihydroxy-olean-12-en-28-oic acid-28-O-beta-D-glucopyranoside (1),
      arjunetin (2), sericoside (3), glucosyl tormentate (4), nigaichigoside F1 (5) and
      arjunglucoside I (6), separately. Compound 1 is a new compound, and compounds 2 
      6 were isolated from A. nitida for the first time.

PMID- 18717339
TI  - [C21 steroids from the stems of Marsdenia tenacissima].
AB  - To study the C21 steroids of the stems of Marsdenia tenacissima (Roxb.) Wight et
      Arn, various chromatography methods were used for the isolation of the
      constituents and their structures were identified by spectral analysis. Eight C21
      steroids were isolated from the CHCl3 extract, which were identified as 11alpha-O
      tigloyl-17beta-tenacigenin B (1), 17beta-tenacigenin B (2), tenacigenoside A (3),
      11alpha-O-2-methylbutyryl-12beta-O-acetyl tenacigenin B (4), tenacissoside H (5),
      marsdenoside A (6), tenacissoside G (7), and tenacissoside I (8). Among them,
      compound 1 is a new compound.

PMID- 18717340
TI  - [A new secoiridoid from the flowers of Jasminum officinale L. var. grandiflorum].
AB  - To study the chemical constituents of the flowers of Jasminum officinale L. var.
      grandiflorum, the compounds were isolated and purified by HPLC, recrystallization
      and chromatography on silica gel and Sephadex LH-20 column. Their structures were
      elucidated on the basis of physicochemical properties and spectral analysis. Six
      secoiridoids were identified as jasgranoside (I), jaspolyoside (II), 8-epi
      kingiside (III), 10-hydroxy-oleuropein (IV), 10-hydroxy-ligstroside (V), oleoside
      7, 11-dimethyl ester (VI). Compound I is a new compound. Compounds II, III, IV, V
      and VI were isolated from Jasminum officinale L. var. grandiflorum for the first
      time.

PMID- 18717342
TI  - [Pharmacokinetics of luteolin from Elsholtzia blanda extracts in rats].
AB  - An RP-HPLC method for determination of luteolin from Elsholtzia blanda Benth.
      extracts in rats' plasma was established and the pharmacokinetics of luteolin in
      rats was studied. Drug blood samples from caudal vein were gotten after oral
      administration of luteolin. Plasma samples were determined by RP-HPLC after being
      deproteinized with trichloroacetic acid and extracted with ethyl acetate. The
      calibration curve was linear in the range of 0.37-47.27 microg x mL(-1). The
      limit of quantification was 0.37 microg x mL(-1). The method recovery of luteolin
      was 93%-99%. The extract recovery was 75%-85%. RSDs of intra-and inter-day
      precisions were less than 5%. The concentration-time curve of luteolin after oral
      administration of Elsholtzia blanda Benth. extracts was fitted to two compartment
      open model. Two factors analysis of variance were adopted in the evaluation of
      gender and time spots for collection of blood. The result suggested that the
      gender-based difference in blood-drug concentrations had statistical
      significance. The metabolite in blood was identified as galcuronide. The method
      is sensitive, specific, accurate, and is appropriate for determination of
      luteolin in vivo.

PMID- 18717341
TI  - [Determination of the allergic impurities in the parenteral injection of Chinese
      traditional medicines containing Salvia miltiorrhiza].
AB  - The residual protein mixture (the content is 4%, approximately), called Salvia
      miltiorrhiza antigen, was extracted from the Salvia miltiorrhiza cruel materials
      by mimicking the alcohol-deposit extracts process. Both rabbits and guinea pigs
      sensitized by Salvia miltiorrhiza could produce specified antibodies. Large
      molecular antigenic impurities were extracted from the Danshen injection and
      Xiangdan injection using the centrifugal filtering method. The test results of
      active systemic anaphylaxis (ASA) and passive cutaneous anaphylaxis (PCA) in
      guinea pigs confirmed that the extracted antigenic impurities could induce the
      anaphylaxis reaction in the animals which were sensitized by the Salvia
      miltiorrhiza antigen. Using the specified antibody produced from rabbits which
      were sensitiyed by Salvia miltiorrhiza, ELISA test method was developed to test
      the residual Salvia miltiorrhiza antigenic materials contained in the parenteral
      Chinese traditional medicines. Calculated as residual protein, the linear range
      was 0.08-5.12 microg x mL(-1) (r2 = 0.9906), the detection limit and quantization
      limit are 0.08 microg x mL(-1) and 0.4 microg x mL(-1), respectively. 308 batches
      of parenteral Chinese traditional medicines containing water-soluable components
      of Salvia miltiorrhiza were tested, and the Salvia miltiorrhiza antigenic
      impurities were spotted in 35 (11.4%) batches of samples. The test results show
      that the extracting process currently used can not remove the Salvia miltiorrhiza
      antigenic impurities completely, and this may be one of the reasons for
      anaphylactic reaction in clinics. The proposed ELISA method can be used for
      improving the manufacture process and for routine quality control of drug
      products.

PMID- 18717343
TI  - [Effect of polyoxyl ether analogous surfactants on the activity of cytochromes
      P450 3A in rats in vivo].
AB  - To evaluate the effects of p-octyl polyethylene glycol phenyl ether (Triton X
      100), polyoxyl 35 caster oil (EL35) and polyoxyl 40 hydrogenated caster oil
      (RH40) on the activity of Cytochrome P450 3A (CYP3 As) in vivo. Rats were
      administered with saline, ketoconazole (75 mg x kg(-1) x d(-1)), Triton X-100 (30
      mg x kg(-1) x d(-1)), EL35 (150 mg x kg(-1) x d(-1)) and RH40 (150 mg x kg(-1) x
      d(-1)) intragastrically for 5 consecutive days, and then given midazolam 10 mg x
      kg(-1) 20 min after the last treatment of ketoconazole or three surfactants with
      the same dose through duodenal administration. Pharmacokinetics parameters for
      midazolam and its metabolite 1'-hydroxymidazolam were estimated from the plasma
      concentration-time data by a noncompartmental approach. The results showed that
      multiple dose administration of Triton X-100, EL35 and RH40 decreased the ratios
      of 1'-hydroxymidazolam and midazolam AUC0-infinity from 1.14 to 0.90, 1.03 and
      0.64, respectively. In contrast, multiple dose administration of ketoconazole
      caused the ratios of 1'-hydroxymidazolam and midazolam a significant decrease to
      0.50. This study indicated that Triton X-100 and EL35 would have no inhibition on
      CYP3A, while RH40 had significant inhibition on CYP3A. Therefore, RH40 might be
      used to prepare drug formulations in pharmaceutical industry and would increase
      the bioavailability of some drugs transformed by CYP3As and further lead to
      significant clinical pharmacologic effects.

PMID- 18717344
TI  - [Molecular identification of heparin from pigs by allele-specific PCR (AS-PCR)
      and amplification refractory mutation system (ARMS)].
AB  - The aim of this study is to develop a convenient and effective method for the
      identification of heparin from pigs (include Sus scrofa domestica Brisson and Sus
      scrofa riukiuanus). Based on sequences of D-loop region of pigs and the other
      animals, two pairs of highly specific primers were designed for distinguishing
      heparin of pigs from other animals. The primers were employed to amplify D-loop
      region of DNA templates extracted from pig and seven other animal species that
      amounted to 49 samples. AS-PCR (allele-specific PCR) and ARMS (amplification
      refractory mutation system) were all suitable for fast identification of heparin
      from pig with anneal temperature at 54-56 degrees C in AS-PCR and with wider
      anneal temperature in ARMS,at 52-58 degrees C. An about 170 bp DNA fragments were
      amplified from separately pigs and whereas no DNA fragment was amplified from
      other samples under the same reaction condition.

PMID- 18717345
TI  - [Induction of apoptosis of the human leukemia cells by arctigenin and its
      mechanism of action].
AB  - This study investigated the effect of arctigenin (ARG) on the induction of
      apoptosis and the putative pathways of its action in HL-60 and K562 cells. MTT
      assay was used to detect the cytotoxic effect of ARG in HL-60 and K562 cells. The
      apoptosis was observed by Hoechst 33258 fluorescence staining and DNA agarose gel
      electrophoresis. Caspase-3 enzyme activity was measured by caspase-3 enzyme
      activity detection kit. The expression of related protein was analyzed by Western
      blotting and the vascular endothelial growth factor (VEGF) level was determined
      by enzyme-linked immunosorbent assay (ELISA). ARG-treated HL-60 cells and K562
      cells exhibited growth inhibition and displayed several features of apoptosis,
      including DNA fragmentation and DNA laddering by agarose gel electrophoresis. It
      was observed that poly-(ADP-ribose) polymeras (PARP) were cleaved to smaller
      molecules and ARG induced upregulation of bax and downregulation of bcl-2 protein
      expression. However, it had no effect on VEGF levels. Taken together, this study
      demonstrated that ARG is a potent inducer of apoptosis and this was accompanied
      by caspase-3 activation and upregulation of bax/bcl-2, which offers a potential
      mechanism for the apoptosis-inducing activity of ARG.

PMID- 18717346
TI  - [Preparation and in vitro study of buagafuran solid dispersions].
AB  - Solid dispersions technique was used to solidify buagafuran and improve
      buagafuran in vitro dissolution and stability. Buagafuran solid dispersions were
      prepared separately using PVPK30, PEG6000 and Poloxamer188 at various weight
      ratios as carriers. The status of buagafuran in solid dispersions was determined
      by using DSC and IR. The solubility, content and in vitro dissolution of pure
      drug and the solid dispersions were detected by using HPLC. When
      buagafuran/carrier was 1:5 or less, the drug existed in a solid dispersion form.
      Three kinds of carriers all can improve buagafuran dispersibility and in vitro
      dissolution. Accelerating experiment showed that buagafuran/PVPK30 < or = 1:10
      solid dispersions was ageing-resistant, and the aspect, content and in vitro
      dissolution did not change after storaged over 3 months, but PEG6000,
      Poloxamer188 and a lower ratio PVPK30 solid dispersions became aged.
      Buagafuran/PVPK30 < or = 1:10 solid dispersions can be developed as buagafuran
      oral drug delivery carrier.

PMID- 18717347
TI  - [Double-step distraction osteogenesis in the reconstruction of unilateral
      mandibular segmental defects after tumor resection].
AB  - OBJECTIVE: To investigate the application of double-step distraction osteogenesis
      in the reconstruction of mandibular segmental defects after tumor resection.
      METHODS: From January 2002 to December 2006, six cases of post-tumor unilateral
      mandibular segmental defects were reconstructed using distraction osteogenesis.
      The mandibular body was lengthened first, following by mandibular ramus
      distraction. RESULTS: No infection or other complication was observed. The
      maximal distraction length reached 55 millimeter in the mandibular body, and 42
      millimeter in the mandibular ramus. The average distraction length was 52
      millimeter in the mandibular body, and 34 millimeter in the mandibular ramus.
      Both the aesthetic and functional result was excellent in all cases. CONCLUSIONS:
      Double-step distraction osteogenesis is effective and easily performed in the
      reconstruction of unilateral mandibular segmental defects with less morbidities
      and complications. There is no need for donor site. However, the treatment period
      is relatively long with three staged operations.

PMID- 18717348
TI  - [Management of complicated midface deficiencies with external distraction].
AB  - OBJECTIVE: To treat complicated midface deficiencies with external distraction
      device. METHODS: Four patients (one with acquired midface hypoplasia, two with
      Crouzon syndrome and one with Parry Romberg) with severe midface deficiencies
      underwent external distraction osteogenesis. After Le Fort III or Le Fort III
      plus I osteotomies were performed, the external distraction devices were
      activated on the 7th postoperative day with a rate of 1 mm per day. The
      distraction devices were removed after consolidation for 3 months. RESULTS: All
      patients completed the distraction treatment. The distraction distance ranged
      from 10 to 14 mm. The appearance of all patients was significantly improved.
      CONCLUSIONS: External distraction osteogenesis provides an effectively treatment
      for patients with severe and complicated midface deficiencies.

PMID- 18717349
TI  - [Changes of different section area at different parts of upper-airway after Le
      Fort III osteotomy].
AB  - OBJECTIVE: To observe the therapeutic effects of Le Fort III osteotomy and
      midface distraction osteogenesis (DO) on the upper-airway narrow. METHODS: Since
      2000, 11 cases (10 cases of Crouzon syndrome and 1 case of Apert syndrome) with
      severe midface deficiency were treated with Le Fort III osteotomy and midface DO.
      The section area of different parts of upper-airway were tested by computer
      assistants image measurement preoperatively and postoperatively. Some patients
      received sleep function monitoring. RESULTS: The face appearance and the function
      of upper-airway improved significantly after Le Fort III osteotomy and Midface
      DO. The section area at the level of posterior nasal spine and uvula increased
      obviously after treatment (P < 0.05), however the section area at the level of
      epiglottis and separation between airway and esophagus were not obviously
      enlarged (P > 0.05). CONCLUSIONS: Midface DO after Le Fort III osteotomy can
      effectively improve the upper-airway narrow, especially the upper part from
      uvula.

PMID- 18717350
TI  - [Clinical application of thoracodorsal artery perforator flaps].
AB  - OBJECTIVE: To analyses the clinical application of thoracodorsal artery
      perforator flaps (TAP). METHODS: We used free or pedicled TAP flaps in 7 patients
      from Aug 2006 to April 2007, The age ranged from 7 to 42 years old, the
      perforator arteries was detected and labeled with a hand held Doppler flowmeter,
      the size of flaps ranged from 6 cm x 9 cm - 12 cm x 16 cm, the flaps designed
      with perforator artery included, all the flaps are based on the first perforator
      artery. RESULTS: All the flaps survived well, no complication occurred with
      lowest donor site morbidity. CONCLUSIONS: The thoracodorsal artery flap with
      latissimus dorsal muscle saved is a thin and reliable flaps with robust of blood
      supply, the flap can reduce significantly donor site morbidity and is a good
      choice for reconstructive surgery.

PMID- 18717351
TI  - [Repeated operation for removement of polyacrylamide hydrogel from breast].
AB  - OBJECTIVE: To investigate the technique of repeated operation for removement of
      polyacrylamide hydrogel from breast. METHODS: 17 cases after uncomplete
      removement of PHG were reoperated through inferior periareolar incision. The PHG
      and affected denatured muscle and gland tissue were removed. RESULTS:
      Preoperative MRI or CT showed PHG distributed diffusely in muscle and gland.
      There was only minimal residual PHG after operation. Histological examination
      showed PHG distributed in the denatured and proliferative fibrous tissue,
      including giant cells, many neutrophilic cells infiltration, and foreign body
      granuloma. The symptoms, such as intramammary pump or nodule, chest and back
      pain, infection, were relieved after operation. CONCLUSIONS: Blinded suction
      technique can not remove PHG completely and can also result in malposition of PHG
      and make the tissue denaturation worse. We suggest open approach to remove the
      PHG and denatured tissue completely through periareolar incision.

PMID- 18717352
TI  - [A rhombus shape excision of the soft palate to treat obstructive sleep apnea
      hypopnea syndrome].
AB  - OBJECTIVE: To explore a surgical treatment for obstructive sleep apnea hypopnea
      syndrome (OSAHS). METHODS: 12 cases were treated during the period from Jan 1998
      to Aug 2006. Partial soft palate was resected in rhombus shape from the middle to
      shorten the soft palate and enlarge the pharyngeal cavity. The uvula was
      reserved. RESULTS: The patients were followed up for six months to five years.
      There was no complication. Good results were achieved in 9 patients. 2 cases got
      some kind of improvement. No improvement happened in one case who received a
      partial tongue resection later. CONCLUSIONS: A rhombus shape excision of the soft
      palate from the middle is effective for the treatment of OSAHS with few
      complication.

PMID- 18717353
TI  - [Anatomy and clinical application of posterior calf fasciocutaneous flap].
AB  - OBJECTIVE: To investigate the blood supply and the clinical application of the
      posterior calf fasciocutaneous flap for repairing the frontal defect of knee
      joint. METHODS: Based on the article review and the anatomical study of the
      posterior calf in 8 cadavers (16 sides), 10 cases with frontal defects of knee
      joints were repaired with island fasciocutaneous flaps which had pedicles of
      lateral superficial sural artery and the lateral sural nerve. RESULTS: The
      anatomical study showed there were three systems of superficial sural blood
      supply- medial, middle and lateral systems. They are originated from popliteal
      artery or from the bilateral sural artery. The lateral superficial sural artery
      was present in 100% of the cadavers. The flaps survived completely in 9 cases,
      except one case with partial necrosis at the one-fourth distal end of the flap.
      The patients were followed up for 6-12 months with good aesthetic and functional
      results. CONCLUSIONS: The posterior calf island fasciocutaneous flap has an
      reliable blood supply and protective sense nerve. The flap is ideal for the
      reconstruction of soft tissue defect around knee joint.

PMID- 18717354
TI  - [Reconstruction of skin defect at frontal hair line with mastoid fasciocutaneous
      island flap].
AB  - OBJECTIVE: To investigate the reconstruction of skin defect at frontal and
      temporal hair line. METHODS: 5 cases with skin defect at frontal and temporal
      hair line were treated with mastoid fasciocutaneous island flap pedicled with
      parietal branch of superficial temporal artery. RESULTS: All the flaps survived
      completely. Hair grew up 5 - 7 days after operation, showing good reconstructed
      hair line. CONCLUSIONS: Mastoid fasciocutaneous island flap is a reliable method
      for reconstruction of skin defect at frontal and temporal hair line.

PMID- 18717355
TI  - [3-dimensional CT cephalometry before and after mandibular angle osteotomy and
      its clinical significance].
AB  - OBJECTIVE: To investigate the change of skeleton structure and masseter after
      mandibular angle osteotomy and its clinical significance in preoperative design.
      METHODS: 3-dimensional CT cephalometry was performed before and after surgery in
      18 cases of prominent mandibular angle. RESULTS: Pre- and post-operative data
      were compared. Significant differences between the pre- and post-operative data
      were found in the mandibular angle, the distance between mandibular angle, length
      of ramus, ectropion angle of mandibular angle, triangle Go-Me-Go, the thickness,
      width and length of masseter. CONCLUSIONS: It indicates the skeleton structure is
      changed and some kind of atrophy happens in the masseter after operation. So we
      suggest partial resection of masseter should be unnecessary for mandibular angle
      osteotomy.

PMID- 18717356
TI  - [Experimental study of repairing skull defect with autogenous cranial bone dust].
AB  - OBJECTIVE: To build animal model of skull defect for the basic research of skull
      defects reconstruction with autogenous cranial bone dust and its relevance to the
      clinical application. METHODS: Three full-thickness parietal skull defects (A, B
      and C) were created in 30 New Zealand white rabbits. The size of all the defects
      was 1 cm in diameter. The defect A was left untreated as control. Defects B and C
      were reconstructed with autogenous cranial bone dust. Two pieces of pyroxylin
      membrane were placed on the top and bottom of the defect B. every 10 rabbits were
      killed for analysis at 4, 8, 12 weeks after operation. RESULTS: Defect A was
      largely repaired with connective tissue. Defect B was repaired rapidly with newly
      formed cancellous bone in the early period, but the following process of the
      growth, remodeling and maturing of the newly-formed cancellous bone was slowly.
      The bone ingrowth in defect C was more mature, but could not repair the defect
      completely, especially in the central zone. The grafted bone dust was absorbed
      gradually. Active angiogenesis could be observed in the newly formed bone. For
      the same defect, new bone had a greater amount of calcium at 12 weeks than at 4
      and 8 weeks after operation (P < 0.05). And the calcium content of new bone was
      higher in defect C than in defect B at 8, 12 weeks after operation (P < 0.05).
      CONCLUSIONS: The osteogenesis and angiogenesis are closely related to the time
      and location. The pyroxylin membrane can significantly promote the formation of
      cancellous bone in defect with autogenous bone dust graft during the early
      period.

PMID- 18717357
TI  - [Experimental studies of VEGF-C gene for the treatment of chronic obstructive
      lymphedema in mouse tail model].
AB  - OBJECTIVE: To study the therapeutic effect of vascular endothelial growth factor
      C (VEGF-C) gene for chronic obstructive lymphedema in mouse tail model which may
      provide a new treatment for lymphedema. METHODS: RT-PCR and immunoabsorption were
      applied to detect VEGF-C gene expression in fibroblasts and secretion of VEGF-C
      protein in COS7 cells respectively after pCDNA3.1 (+) VEGF-C transfection. A
      mouse tail model of chronic obstructive lymphedema was created. Then the pcDNA3.1
      VEGF-C plasmid was injected into the tail. The effect of modulating
      lymphangiogenesis was observed. RESULTS: Compared with control group,
      overexpression of VEGF-C enhanced lymphangiogenesis in vivo and mouse tail skin
      suffering chronic obstructive lymphedema was improved by VEGF-C gene
      significantly. CONCLUSIONS: VEGF-C can improve the lymphedema through enhancing
      lymphangiogenesis.

PMID- 18717358
TI  - [A new model of skin avulsion injuries in rats].
AB  - OBJECTIVE: To create a stable and reliable model of skin avulsion in rats.
      METHODS: 30 male, SD rats were randomly divided into axial pattern skin flap (9
      cm x 3 cm) group and random pattern skin flap group (6 cm x 4 cm), each having
      the control groups and avulsion groups. Flaps were subjected to avulsion force of
      6 kg in axial pattern skin flaps or 8 kg in random pattern skin flaps, and the
      lasting time was 8 s or 12 s, respectively. Retraction of wounds and necrosis of
      skin flaps were observed. RESULTS: There was more significant wound retraction in
      avulsion groups than that in control groups on post-operation day 7 (P < 0.05).
      The proportion of the wound retraction increased by 1 fold in avulsion groups on
      post-operation day 14 as compared to post-operation day 7 (P < 0.01).
      Interestingly, necrosis of partial or most of skin flaps was observed in all
      animals of avulsion groups, while slight necrosis happened in one of six in
      control animals. The necrosis area of flaps was 38% - 77% when avulsed for 8 s,
      and was 40% - 80% when avulsed for 12 s in axial pattern skin flaps. However, the
      necrosis area in random pattern skin flaps was smaller than that in axial pattern
      skin flaps, from 17% - 40% when avulsed for 8 s to 24% - 43% when avulsed for 12
      s. CONCLUSIONS: It might be possible to create animal model of skin avulsion
      injuries with rats.

PMID- 18717359
TI  - [Experimental research of correlation between anatomy structure of rabbit ear and
      creating hypertrophic scar animal model].
AB  - OBJECTIVE: To observe the anatomy structure of rabbit ear and the effect of
      different operation methods and post-operative treatments on the formation of
      hypertrophic scar. METHODS: The experimental animals were 25 New Zealand white
      rabbits. 6 pieces of full skin specimens were obtained from each of the ears in 5
      rabbits for histological examination. 6 full-thickness skin wounds (d = 8 mm)
      were made on different sites of ventral side of each ear in the other 20 rabbits.
      The total number of the wounds was 240. 120 wounds in 10 rabbits were divided
      into 4 groups randomly to receive different treatments on day 7 postoperatively.
      No treatment was performed in the other 120 wounds. The wounds healing and the
      scar formation were observed for six months. The scars were harvested 4 weeks and
      8 weeks after operation for pathologic examination and measurement of scar
      elevation index (SEI). RESULTS: Histological analysis showed that the anatomy
      structure was different in different sites of the rabbit ear. The best sites for
      creating hypertrophic scar model were on the medial margin of the middle- and
      inferior part of ear. The depth of the wound should reach the cartilage membrane
      of the ear to facilitate the formation of hypertrophic scar. The second strip
      crust on day 7 postoperatively enhanced the wounds healing and minimized the scar
      proliferation and hypertrophy. CONCLUSIONS: There is a close correlation between
      the anatomy structure of the ear and the creation of hypertrophic scar animal
      model. The wound site, the depth of wound and the post-operative treatment will
      affect the formation of hypertrophic scar. The study can help to improve the
      successful rate of creating hypertrophic scar animal model.

PMID- 18717360
TI  - [Constructing of smooth muscle layers of tissue engineered blood vessel in a
      bioreactor].
AB  - OBJECTIVE: To investigate the feasibility of in vitro constructing tissue
      engineered blood vessels in bioreactor. METHODS: Cell-PGA (polyglycolic acid)
      complex was constructed by seeding smooth muscle cells isolated from canine
      carotid artery on PGA unwoven fibers. The cell-PGA complex was cultured in a
      bioreactor (pulse rate = 75/min, radical distension < 5%). After three or six
      weeks in vitro culture, engineered tissues were harvested and tested. RESULTS:
      Grossly,the experimental groups showed a tubular structure with a round lumen and
      good elasticity. Histological staining revealed smooth muscle fibers layers and
      dense elastic fibers presented in the engineered vessel wall. Bands of smooth
      muscle fibers and continuous endothelial cells layer were detected by the immuno
      histological staining. In contrast, the control group took on poor elasticity,
      collapsed lumen and pale surface in the gross observation. In addition, its
      arrangement of smooth muscle fibers and elastic fibers was random and
      disorganized by histological observation, which was also confirmed by the
      immunohistological staining. The structure of 6 weeks TEBVs was more mature than
      that of 3 weeks and the biomechanical property of dynamic ones was as much as 60%
      of the normal one. CONCLUSIONS: Blood vessel with good elasticity can be
      constructed in a bioreactor by tissue engineering approach.

PMID- 18717361
TI  - [The relationship between RUNX3 gene mutation and keloid].
AB  - OBJECTIVE: To study the mutation in RH120480 fragment of RUNX3 gene among the
      Chinese patients with keloid. METHODS: 20 samples of keloids were collected with
      each patient's venous blood sample as normal control group. The genomic DNA was
      extracted from each sample. RH120480 fragment of RUNX3 gene was amplified by
      Polymerase Chain Reaction (PCR). The amplification products were analyzed by
      denaturing high-performance liquid chromatography (DHPLC). Some fragments were
      sequenced directly and then compared with the GenBank data. RESULTS: By DHPLC,
      the results of all the blood samples showed single chromatographic peak
      indicating homoduplexes, meanwhile the results of keloid tissue samples showed
      double peak indicating heteroduplexes. Through gene sequencing, 19 cases showed
      gene mutation among the 20 samples of keloid. The mutation incidence was 95%. Two
      mutation sites were detected including base A absence in 96th sites and base C
      insert in 279th sites. The base A absence rate was 90% (18/20) in keloid group,
      and 10% (2/20) in control group. The base C insert mutation rate was 95% (19/20)
      in keloid group, and 0% (0/20) in control group. There was significant difference
      in the mutation rate between two groups on the two mutation sites. CONCLUSIONS:
      There is a strong correlation between the RH120480 fragment of RUNX3 gene
      mutation and Keloid. RUNX3 gene could be possibly a scar suppressor gene (SSG).

PMID- 18717362
TI  - [Anatomic study of intramuscular nerve and blood vessel in forearm muscles: an
      anatomical study].
AB  - OBJECTIVE: To study the distribution of intramuscular nerve and blood vessels in
      forearm muscles and to discuss the possibility of dividing the forearm muscles
      into independent functional units. METHODS: (1) The muscles were dissected in 10
      forearms from 5 fresh adult human cadavers and stained with the Sihler's nerve
      staining; (2) The blood vessels were studied in eight forearm muscles from 4
      fresh adult human cadavers with irrigation of a mixture of 30% barium sulfate and
      gelatin from brachial artery and then X-photographed. All pictures were compared
      to study the intramuscular distribution of nerve and blood vessels. RESULTS: The
      intramuscular nerve branches were stained purple-black and visualized clearly.
      The muscles were classified into three types according to the distribution
      characters of intramuscular nerve and blood vessels. And the types of muscles
      could be further subdivided into a and b subtypes. CONCLUSION: According to the
      neurovascular distribution, the forearm muscles in type II a and type III a can
      be divided into independent function units for muscle functional transplantation.

PMID- 18717363
TI  - The coproduction of moral discourse in U.S. community psychiatry.
AB  - Anthropologists often criticize the discipline of bioethics because its remote,
      abstract theories fail to capture how front-line clinicians experience and
      resolve moral uncertainty. The critique overlooks, however, the ways that
      everyday, emergent moral discourse is influenced--over time and through several
      mediations--by formal ethical notions. High-order ethical pronouncements become
      sedimented into the conditions of work, illustrated in this article by a two-year
      ethnographic study of Assertive Community Treatment (ACT), a popular mode of
      outpatient psychiatric services. ACT clinicians' moral unease when they break the
      confidentiality of patients is connected to high-order debates, dating back 35
      years, about ensuring patients' autonomy without abandoning them. These debates
      originally spurred the invention of ACT, and they get braided into today's moral
      discourse through several mediations: regulatory paperwork, the mandates and
      micropolitics of staff-patient interactions, and the idealized self-image of
      front-line staff. This article shows how everyday moral talk is coproduced by
      both the immediate contexts of clinical work and the categories of formal
      bioethics.

PMID- 18717364
TI  - Cross-cultural perspectives on physician and lay models of the common cold.
AB  - We compare physicians and laypeople within and across cultures, focusing on
      similarities and differences across samples, to determine whether cultural
      differences or lay-professional differences have a greater effect on explanatory
      models of the common cold. Data on explanatory models for the common cold were
      collected from physicians and laypeople in South Texas and Guadalajara, Mexico.
      Structured interview materials were developed on the basis of open-ended
      interviews with samples of lay informants at each locale. A structured
      questionnaire was used to collect information from each sample on causes,
      symptoms, and treatments for the common cold. Consensus analysis was used to
      estimate the cultural beliefs for each sample. Instead of systematic differences
      between samples based on nationality or level of professional training, all four
      samples largely shared a single-explanatory model of the common cold, with some
      differences on subthemes, such as the role of hot and cold forces in the etiology
      of the common cold. An evaluation of our findings indicates that, although there
      has been conjecture about whether cultural or lay-professional differences are of
      greater importance in understanding variation in explanatory models of disease
      and illness, systematic data collected on community and professional beliefs
      indicate that such differences may be a function of the specific illness. Further
      generalizations about lay-professional differences need to be based on detailed
      data for a variety of illnesses, to discern patterns that may be present.
      Finally, a systematic approach indicates that agreement across individual
      explanatory models is sufficient to allow for a community-level explanatory model
      of the common cold.

PMID- 18717365
TI  - Before your very eyes: illness, agency, and the management of Tourette Syndrome.
AB  - In this article, I examine the ways that people with Tourette Syndrome (TS)
      manage the motor and vocal tics characteristic of this neurological disorder. To
      mitigate the powerful stigmas associated with TS, individuals must either remove
      tics from public view or strive to recast the way that they are perceived.
      Drawing on ethnographic research with TS sufferers in Indiana, I elaborate three
      strategies by which this is done, strategies referred to here as displacement,
      misattribution, and contextualization. These processes strongly affect both the
      symptoms themselves and the subjective experience of the illness. They also
      affect the perception of TS in the larger culture, associating the disease with
      florid symptoms like cursing--symptoms that, although not at all typical of TS,
      are the ones most resistant to these kinds of management. These patterns
      highlight how individual agency may actively shape the cultural construction of
      illness.

PMID- 18717366
TI  - Climate change impacts on seals and whales in the North Atlantic Arctic and
      adjacent shelf seas.
AB  - In a warmer Arctic, endemic marine mammal species will face extreme levels of
      habitat change, most notably a dramatic reduction in sea ice. Additionally, the
      physical environmental changes, including less ice and increased water (and air)
      temperatures will result in alterations to the forage base of arctic marine
      mammals, including density and distributional shifts in their prey, as well as
      potential losses of some of their traditionally favoured fat-rich prey species.
      In addition they are likely to face increased competition from invasive temperate
      species, increased predation from species formerly unable to access them in areas
      of extensive sea ice or simply because the water temperature was restrictive,
      increased disease risk and perhaps also increased risks from contaminants. Over
      the coming decades it is also likely that arctic marine mammals will face
      increased impacts from human traffic and development in previously inaccessible,
      ice-covered areas. Impacts on ice-associated cetaceans are difficult to predict
      because the reasons for their affiliation with sea ice are not clearly
      understood. But, it is certain that ice-breeding seals will have marked, or
      total, breeding-habitat loss in their traditional breeding areas and will
      certainly undergo distributional changes and in all probability abundance
      reductions. If species are fixed in traditional spatial and temporal cycles, and
      are unable to shift them within decadal time scales, some populations will go
      extinct. In somewhat longer time frames, species extinctions can also be
      envisaged.

PMID- 18717367
TI  - Effects of climate change on polar bears.
AB  - In this article, we review the effects on polar bears of global warming that have
      already been observed, and try to evaluate what may happen to the polar bears in
      the future. Many researchers have predicted a wide range of impacts of climate
      change on polar bear demography and conditions. A predicted major reduction in
      sea ice habitat will reduce the availability of ice associated seals, the main
      prey of polar bears, and a loss and fragmentation of polar bear habitat will
      ultimately lead to large future reductions in most subpopulations. It is likely
      that polar bears will be lost from many areas where they are common today and
      also that the total population will change into a few more distinctly isolated
      populations.

PMID- 18717368
TI  - Global warming and effects on the Arctic fox.
AB  - We predict the effect of global warming on the arctic fox, the only endemic
      terrestrial predatory mammals in the arctic region. We emphasize the difference
      between coastal and inland arctic fox populations. Inland foxes rely on peak
      abundance of lemming prey to sustain viable populations. In the short-term,
      warmer winters result in missed lemming peak years and reduced opportunities for
      successful arctic fox breeding. In the long-term, however, warmer climate will
      increase plant productivity and more herbivore prey for competitive dominant
      predators moving in from the south. The red fox has already intruded the arctic
      region and caused a retreat of the southern limit of arctic fox distribution
      range. Coastal arctic foxes, which rely on the richer and temporally stable
      marine subsidies, will be less prone to climate-induced resource limitations.
      Indeed, arctic islands, becoming protected from southern species invasions as the
      extent of sea ice is decreasing, may become the last refuges for coastal
      populations of Arctic foxes.

PMID- 18717369
TI  - Butterflies as indicators of climate change.
AB  - In Britain, most butterfly species reach the limit of their range due to climate.
      Such species are the ones most likely to show rapid adaptations to climate
      change. There are indications that several butterfly species are adapting and
      that these insects make good indicators of the likely effects of climate change
      on other animals.

PMID- 18717370
TI  - Climate change and the microbiology of the Antarctic Peninsula region.
AB  - Antarctic terrestrial ecosystems are cold, dry, low nutrient environments, with
      large temperature fluctuations and paradoxically low levels of water
      availability. These extreme environments are dominated by microorganisms
      (viruses, archaea, eubacteria, fungi and microsporidia, alveolata, stmramenopila,
      rhodophyta, green algae and protists), which can either tolerate or are adapted
      to exploit unfavourable growth conditions. However, climate change is altering
      the growth environment in Antarctica, and so selection pressures on these
      microorganisms are changing which, in turn, might affect microbial activity in
      key processes such as biogeochemical cycling. Although the direct effect of a
      change in, for example, temperature, is known for very few Antarctic
      microorganisms, molecular techniques (to monitor population structure) and
      genomic techniques (to identify specific gene function) are starting to give us
      an insight into what the potential effects of climate change might be at the
      cellular level. The key to how microorganisms respond to such change depends upon
      the rate and magnitude of the change along with the physiological capability of
      microorganisms to adapt or tolerate those changes. Here we will examine a number
      of case studies in which the effects of factors such as temperature, nutrient
      availability, grazing, salinity, seasonal cycle and carbon dioxide concentration
      have each been demonstrated to affect bacterial community structure in polar and
      alpine ecosystems. The results suggest that the spatial distribution of genetic
      variation and, hence, comparative rates of evolution, colonization and extinction
      are particularly important when considering the response of microbial communities
      to climate change.

PMID- 18717371
TI  - Gingival grafting in periodontal practice: results of 103 consecutive surgeries
      in 82 patients.
AB  - A consecutive series of 103 surgeries in 82 patients was studied from the normal
      clinical population of a periodontal specialty practice. Four different
      techniques were employed: free gingival grafts, free connective tissue grafts,
      pedicle flaps, and combined techniques. Gingival augmentation using free gingival
      grafts was the most predictable, with 100% of cases showing a gain of > or = 3
      mm. The average root coverage was 2.47 mm overall but was most predictable with a
      combined technique, with 93% gaining > or = 2 mm. Miller Class 4 cases were most
      predictably treated with pedicle flaps and a combined technique. Smokers and
      patients with more complex sites showed less improvement. Mandibular central
      incisors and maxillary canines were the most commonly grafted teeth.

PMID- 18717372
TI  - Distraction osteogenesis for ridge augmentation: prevention and treatment of
      complications. thirty case reports.
AB  - Distraction osteogenesis (DO) is the latest addition to the variety of alveolar
      ridge augmentation procedures used to increase the volume of bone prior to
      implant placement. Thirty DO procedures were performed in 30 patients using 17
      intraosseous and 13 extraosseous devices to augment deficient alveolar ridges.
      Fifty-five implants placed in the distracted bone were followed for a period of
      34 to 60 months after loading. Five implants failed, for a 90.9% success rate.
      Vertical augmentation ranged from 3.5 to 13.0 mm (average, 7.8 mm). At least one
      complication was encountered, requiring additional hard or soft tissue surgery,
      in each of the 30 reported cases. This paper reviews complications encountered in
      the DO-treated patients, suggesting solutions and measures to prevent these
      problems.

PMID- 18717373
TI  - Evaluation of peri-implant bone loss around platform-switched implants.
AB  - This clinical and radiographic prospective study evaluated bone loss around two
      piece implants that were restored according to the platform-switching protocol.
      One hundred thirty-one implants were consecutively placed in 45 patients
      following a nonsubmerged surgical protocol. On 75 implants, a healing abutment 1
      mm narrower than the implant platform was placed at the time of surgery. On the
      remaining implants, a healing abutment of the same diameter as the implant was
      inserted. All implants were positioned at the crestal level. Clinical and
      radiographic examinations were performed prior to surgery, at the end of surgery,
      8 weeks after implant placement, at the time of provisional prosthesis insertion,
      at the time of definitive prosthesis insertion, and 12 months after loading. The
      data collected showed that vertical bone loss for the test cases varied between
      0.6 mm and 1.2 mm (mean: 0.95 +/- 0.32 mm), while for the control cases, bone
      loss was between 1.3 mm and 2.1 mm (mean: 1.67 +/- 0.37 mm). These data confirm
      the important role of the microgap between the implant and abutment in the
      remodeling of the peri-implant crestal bone. Platform switching seems to reduce
      peri-implant crestal bone resorption and increase the long-term predictability of
      implant therapy.

PMID- 18717374
TI  - The effect of all-ceramic and porcelain-fused-to-metal restorations on marginal
      peri-implant soft tissue color: a randomized controlled clinical trial.
AB  - The aim of this study was to test the color-change effect of all-ceramic
      restorations compared with porcelain-fused-to-metal (PFM) restorations on
      marginal peri-implant soft tissue. Thirty patients were randomly divided into 2
      groups of 15 subjects each. The all-ceramic group received all-ceramic crowns on
      aluminum oxide-based abutments, while the PFM group received crowns on titanium
      or gold abutments. A reflectance spectrophotometer was used to measure the color
      difference (deltaE(Implant)) between the midfacial peri-implant mucosa before and
      after restoration insertion. The color difference (deltaE(Tooth-implant)) between
      the midfacial peri-implant mucosa and the gingival margin of the corresponding
      neighboring tooth was tested. The mucosal thickness was measured midfacially
      around the implant (MT(Implant)) and neighboring tooth (MT(Tooth)).
      deltaE(Implant) values were similar for the all-ceramic (7.4 +/- 2.7) and PFM
      groups (7.6 +/- 2.8). The all-ceramic group induced significantly less visible
      mucosal color change (3.4 +/- 1.4) compared to the PFM group (5.2 +/- 2.3). The
      MT(Implant) value of the all-ceramic group was 3.4 +/- 0.8 mm, while that of the
      PFM group was 2.9 +/- 0.9 mm, which was not significantly different. Significant
      differences were found when comparing MT(Implant) (3.1 +/- 0.9) and MT(Tooth)
      (1.2 +/- 0.3) values for test and control groups. All-ceramic restorations
      revealed a better color match to the neighboring teeth than PFM restorations.

PMID- 18717375
TI  - Osseous resective surgery: long-term case report.
AB  - This case report evaluated the long-term effects of osseous resective therapy in
      the treatment of a patient with moderately advanced periodontal disease. In 1984,
      the patient underwent initial therapy followed by a periodontal surgical phase
      consisting of osseous recontouring with an apically positioned flap. After 20
      years, in 2003, the patient presented with a traumatic complication. An
      exploratory surgery revealed a fracture on the roof of the pulp chamber on the
      maxillary left first molar. The buccal roots were resected, preserving the
      palatal root, and a reevaluation of the long-term outcome of osseous resective
      surgery was performed. It is suggested that the positive treatment result is the
      consequence of the reestablishment of tissue morphology favorable for oral
      hygiene and plaque control by the patient.

PMID- 18717376
TI  - Molar uprighting with extrusion for implant site bone regeneration and
      improvement of the periodontal environment.
AB  - This case report describes the treatment of a 55-year-old man who presented with
      a missing maxillary first molar and mesially inclined neighboring second molar
      with a severe circumferential bone defect. After bone regeneration therapy with
      bone grafting, the second molar was uprighted orthodontically to improve the
      inclination and crown-to-root ratio. These treatments minimized the bone defect
      and developed a suitable site for an implant in the first molar position. An
      interdisciplinary approach using periodontal, orthodontic, and prosthodontic
      treatments can create a more predictable and maintainable situation.

PMID- 18717377
TI  - ABC sinus augmentation classification.
AB  - Edentulism in the posterior maxilla can present with compounding variables that
      make it a difficult region to restore with implants. Pneumatization of the sinus
      floor is typically accounted for during surgical treatment planning, but other
      factors such as horizontal ridge deficiency and vertical defects may be
      overlooked. This report reviews the different classifications used to treat the
      posterior maxilla and introduces a new system that incorporates all factors
      critical for implant success. Class A represents abundant bone with > or = 10 mm
      bone height below the sinus floor and > or = 5 mm bone width, allowing proper
      implant placement. Class B indicates barely sufficient bone with 6 to 9 mm bone
      height below the sinus floor, and this can be further subclassified into division
      h (horizontal defect; < 5 mm bone width), division v (vertical defect; > 3 mm
      away from cementoenamel junction), and division c (combined horizontal and
      vertical defect). Class C indicates compromised bone with < or = 5 mm bone height
      below the sinus floor, and this can also be subclassified similar to Class B. The
      ABC classification is a simple system to guide clinicians in proper implant
      treatment of the posterior maxilla.

PMID- 18717378
TI  - A photoelastic and strain-gauge analysis of interface force transmission of
      internal-cone implants.
AB  - The objective of this study was to compare force transmissions in the peri
      implant bone region of implants with various conical implant-abutment mating
      designs. Photoelastic models of solitary Bicon, Astra Tech, and synOcta and
      monoblock ITI implants were fabricated. Static vertical and 20-degree oblique
      forces of 75 N were applied on the implants in separate loading cases, and the
      generation of isochromatic fringes was observed and photographed in the field of
      a circular polariscope. Three-element strain gauges were bonded on the models in
      close proximity to the implants. Under the same loading protocol, the strain
      gauge signals were digitized by a data-acquisition system and displayed on a
      computer using corresponding software at a sample rate of 10 kHz, and the
      principal strains were calculated. Isochromatic fringe orders around ITI and
      Astra Tech implants were similar at the collar region and slightly higher than
      around the Bicon implant under both loading conditions. Strains around the Bicon
      implant were lower than those around all implants tested under vertical loading
      (P < .05), whereas the strains around both ITI implants were similar and lower
      than those around the Astra Tech implant (P < .05). Under oblique loading,
      strains around both ITI implants were higher than those around other implants
      tested (P < .05). However, these differences do not seem to have any clinical
      relevance. Internal-cone implants have similar interface force transfer
      characteristics that resemble a one-part implant. To reduce stresses in the peri
      implant region, implant diameter may be more effective than the type of implant.

PMID- 18717379
TI  - Sinus floor elevation using an osteotome technique without grafting materials or
      membranes.
AB  - This retrospective study aimed to radiographically assess sinus floor remodeling
      after using a modified osteotome technique without graft materials or membranes.
      After pilot drilling, residual bone was fractured and raised with the
      schneiderian membrane to the final implant length using osteotomes. Self-tapping
      implants were placed, and restorations were placed 6 months later. Twenty-four
      patients were available for follow-up after a mean observation period of 17.6 +/-
      8.4 months. The implant survival rate at that time was 100%. Bone filling around
      the implants was measured and compared with baseline digital radiographs. New
      bone formation was 86.3% +/- 22.1% mesially and 89.7% +/- 13.3% distally. In nine
      cases, digital volume tomography was used to verify regeneration. Within the
      limitations of this study, use of the schneiderian membrane led to considerable
      bone regeneration, and good clinical success was achieved despite the omission of
      graft materials.

PMID- 18717380
TI  - Harvesting bone in the recipient sites for ridge augmentation.
AB  - A modified ridge augmentation technique is introduced for augmenting deficient
      alveolar ridges in preparation for endosseous implant placement. The technique is
      based on the principles for guided bone regeneration, in which a created space is
      kept isolated from the surrounding soft tissues by a resorbable membrane with an
      excellent extended resorption profile, thus permitting the accrual of bone
      formative elements into the graft site. The absorbable membrane is propped up by
      an autogenous mixture of native corticocancellous bone cores taken in the graft
      site and reduced to smaller particle sizes and osseous coagulum collected in bone
      traps and with a special bone scraper. The major advantage of this technique is
      that all the autogenous bone graft material is obtained from the actual graft
      site, avoiding second remote intra- or extraoral surgical sites and attendant
      morbidities. Ridges augmented with this technique permit optimal endosseous
      implant placement.

PMID- 18717381
TI  - Probe-specific proportion task repetition effects on switching costs.
AB  - In two experiments, participants were presented with successive presentations of
      animal names (e.g., GORILLA, WHALE)--a prime display followed by a probe display.
      In response to each display, participants judged either the typical habitat or
      the relative size of those animals, repeating the same task in response to both
      displays on half of the experimental trials and switching from one task to the
      other on the other half of trials. Our results demonstrate that switch costs can
      be reduced when either the probe's identity or its location is predictive of a
      change in task. This result establishes that the presentation of a stimulus can
      serve as a rapid cue for facilitating a switch in task, independent of processes
      occurring both at the time of the prime task and during the intervening period
      between the prime and probe tasks. We discuss the implications of these results
      for prevailing explanations of task switching costs.

PMID- 18717382
TI  - Dividing attention across feature dimensions in statistical processing of
      perceptual groups.
AB  - Statistical processing has been shown in the perception of several visual
      dimensions, including size, speed, direction of motion, and orientation. Chong
      and Treisman (2005) found no decrement when people simultaneously averaged two
      sets on a single dimension, size. What happens when attention is divided between
      different dimensions? In two experiments, we investigated judgments of mean size
      and speed, either within the same objects or in two separate sets. In a third, we
      examined judgments of mean size and orientation in two different sets. All three
      experiments suggest a decrement in performance when attention is shared between
      two dimensions, especially when they are carried by two different sets of
      objects.

PMID- 18717383
TI  - Audiovisual synchrony and temporal order judgments: effects of experimental
      method and stimulus type.
AB  - When an audio-visual event is perceived in the natural environment, a physical
      delay will always occur between the arrival of the leading visual component and
      that of the trailing auditory component. This natural timing relationship
      suggests that the point of subjective simultaneity (PSS) should occur at an
      auditory delay greater than or equal to 0 msec. A review of the literature
      suggests that PSS estimates derived from a temporal order judgment (TOJ) task
      differ from those derived from a synchrony judgment (SJ) task, with (unnatural)
      auditory-leading PSS values reported mainly for the TOJ task. We report data from
      two stimulus types that differed in terms of complexity--namely, (1) a flash and
      a click and (2) a bouncing ball and an impact sound. The same participants judged
      the temporal order and synchrony of both stimulus types, using three experimental
      methods: (1) a TOJ task with two response categories ("audio first" or "video
      first"), (2) an SJ task with two response categories ("synchronous" or
      "asynchronous"; SJ2), and (3) an SJ task with three response categories ("audio
      first," "synchronous," or "video first"; SJ3). Both stimulus types produced
      correlated PSS estimates with the SJ tasks, but the estimates from the TOJ
      procedure were uncorrelated with those obtained from the SJ tasks. These results
      suggest that the SJ task should be preferred over the TOJ task when the primary
      interest is i n perceived audio-visualsynchrony.

PMID- 18717384
TI  - A face recognition by similarity (FRBS) conjecture.
AB  - Cohen (1963) investigated free recall in two lists of words. The first contained
      unrelated words. The second comprised words drawn from several semantic
      categories, where the number of categories was equal to the number of words in
      the first list. He found that recall of unrelated words was equal to the recall
      of categories. The face recognition by similarity (FRBS) conjecture proposes that
      this relation cannot be applied to face recognition. Following Cohen's design,
      two different experimental situations for generating two target faces were
      constructed. The findings showed that the number of correct recognitions of
      specific facial features belonging to the first target face (e.g., nose, chin)
      was greater than or equal to the number of categories of visually similar facial
      features belonging to the second target face (e.g., different long noses, round
      chins). In addition, theoretical underpinnings for the FRBS conjecture were
      suggested.

PMID- 18717386
TI  - Modality-specific and amodal sources of interference in the attentional blink.
AB  - When two masked targets (T1 and T2) are visually or auditorily presented in rapid
      succession, processing of T1 produces an attentional blink (AB)--that is, a
      transient impairment of T2 identification. The present study was conducted to
      compare the relative impact of masking T1 and T2 between vision and audition.
      Within a rapidly presented sequence, each of the two verbal targets,
      discriminated by their offset (Experiment 1) or their onset (Experiment 2), could
      be followed by either a single item, acting as a mask, or a blank gap. Masking of
      T2 appeared to be necessary for the occurrence of the AB for both the visual and
      the auditory modality. However, whereas masking of T1 affected the expression of
      the visual AB in both experiments, the same effect was observed in the auditory
      modality only when the targets varied at the onset. These results provide further
      evidence that processing auditory and visual information is restricted by similar
      attentional limitations but also suggest that these limits are constrained by
      properties specific to each sensory system.

PMID- 18717385
TI  - A role for the perceptual representation memory system in category learning.
AB  - There is growing evidence that working memory, episodic/semantic memory, and
      procedural memory all play important roles in at least some types of category
      learning. Little is known, however, about the role of the perceptual
      representation memory system (PRS). Two experiments are reported that provide
      evidence that under certain conditions, the PRS, by itself, is sufficient to
      mediate category learning. Both experiments compared performance in (A, not A)
      and (A, B) prototype distortion category-learning tasks, in which category
      exemplars are created by randomly distorting one category prototype in the (A,
      not A) conditions or two prototypes in the (A, B) conditions. Results showed that
      (A, not A) performance was more sensitive to prototype similarity and less
      affected by the removal of feedback than (A, B) performance. These results
      support the hypothesis that (A, not A) performance was mediated by the PRS, but
      that (A, B) performance recruited other memory systems.

PMID- 18717387
TI  - Absolute localization of vibrotactile stimuli on the torso.
AB  - Vibrotactile mobility systems present spatial information such as the direction
      of a waypoint through a localized vibration on the torso. Using these systems
      requires the ability to determine the absolute location of the stimulus. Because
      data are available only on the ability to determine the relative location of
      stimuli on the torso, we developed a novel method for measuring absolute
      localization on the basis of triangulation. For 15 observers, we calculated the
      subjective location of visual and tactile stimuli on the frontal half of the
      torso. The size of the 95% confidence intervals around the subjective tactile
      locations is about the size of the stimuli (1.66 cm) and is slightly larger than
      that around the subjective visual locations (mean difference, 0.17 cm). The error
      in tactile judgments over and above that in the visual judgments is present only
      for locations near the body midline. When the subjective visual and tactile
      locations are not co-located, the difference can best be described by a shift
      along the radius from the body midaxis. The same holds for the differences
      between the veridical and the subjective locations. Therefore, the difference
      between the veridical and the subjective directions of a stimulus is small. The
      results make us believe that stimulus locations on the torso are coded in polar
      coordinates of which the angle is perceptual invariant and the distance is less
      important, probably because it varies with changes in, among other things,
      posture and breathing.

PMID- 18717388
TI  - Distinctive shapes benefit short-term memory for color associations, but not for
      color.
AB  - In four experiments, we examined the effect of pairing colors with either
      homogeneous or heterogeneous shapes on a short-term memory task. In Experiment 1,
      we found no differences in color memory for displays in which colors were each
      associated with different shapes, paired with individual homogeneous shapes, or
      paired with heterogeneous shapes. In contrast, in Experiment 2, we found that
      when participants were asked to remember the specific pairings of colors, memory
      was improved for heterogeneous-shape displays. The benefit for heterogeneous
      shapes appears to be memorial, rather than one that occurs at the time of
      encoding (Experiment 3) or retrieval (Experiment 4). The present study suggests
      that distinctive shapes can be used to help bind color associations in visual
      short-term memory.

PMID- 18717389
TI  - Poor shape perception is the reason reaches-to-grasp are visually guided online.
AB  - Both judgment studies and studies of feedforward reaching have shown that the
      visual perception of object distance, size, and shape are inaccurate. However,
      feedback has been shown to calibrate feedfoward reaches-to-grasp to make them
      accurate with respect to object distance and size. We now investigate whether
      shape perception (in particular, the aspect ratio of object depth to width) can
      be calibrated in the context of reaches-to-grasp. We used cylindrical objects
      with elliptical cross-sections of varying eccentricity. Our participants reached
      to grasp the width or the depth of these objects with the index finger and thumb.
      The maximum grasp aperture and the terminal grasp aperture were used to evaluate
      perception. Both occur before the hand has contacted an object. In Experiments 1
      and 2, we investigated whether perceived shape is recalibrated by distorted
      haptic feedback. Although somewhat equivocal, the results suggest that it is not.
      In Experiment 3, we tested the accuracy of feedforward grasping with respect to
      shape with haptic feedback to allow calibration. Grasping was inaccurate in ways
      comparable to findings in shape perception judgment studies. In Experiment 4, we
      hypothesized that online guidance is needed for accurate grasping. Participants
      reached to grasp either with or without vision of the hand. The result was that
      the former was accurate, whereas the latter was not. We conclude that shape
      perception is not calibrated by feedback from reaches-to-grasp and that online
      visual guidance is required for accurate grasping because shape perception is
      poor.

PMID- 18717390
TI  - Visual search is not blind to emotion.
AB  - A series of three visual search tasks revealed more efficient search for hostile
      than for peaceful faces among neutral face distractors. Given that this effect
      has been observed inconsistently in prior literature, meta-analytic methods were
      employed for evaluating data across three experiments in order to develop a more
      valid estimate of the potentially small effect size. Furthermore, in the present
      experiments, different emotional meanings were conditioned to identical faces
      across observers, thus eliminating confounds between the physical characteristics
      and the emotional valences of the face stimuli. On the basis of the present
      findings, we argue that the visual system is capable of determining a face's
      emotional valence before the face becomes the focus of attention, and that
      emotional valence can be used by the visual system to determine subsequent
      attention allocation. However, meta-analytic results indicate that emotional
      valence makes a relatively small contribution to search efficiency in the present
      search context.

PMID- 18717391
TI  - Perceptual experience and posttest improvements in perceptual accuracy and
      consistency.
AB  - Two experiments investigated the relationship between perceptual experience
      (during practice) and posttest improvements in perceptual accuracy and
      consistency. Experiment 1 investigated the potential relationship between how
      often knowledge of results (KR) is provided during a practice session and
      posttest improvements in perceptual accuracy. Experiment 2 investigated the
      potential relationship between how often practice (PR) is provided during a
      practice session and posttest improvements in perceptual consistency. The results
      of both experiments are consistent with previous findings that perceptual
      accuracy improves only when practice includes KR and that perceptual consistency
      improves regardless of whether practice includes KR. In addition, the results
      showed that although there is a relationship between how often KR is provided
      during a practice session and posttest improvements in perceptual accuracy, there
      is no relationship between how often PR is provided during a practice session and
      posttest improvements in consistency.

PMID- 18717392
TI  - Using temporal order to identify spatial reference frames.
AB  - A new method for identifying spatial reference frames is described and applied to
      the study of spatial span. In this method, a spatial sequence is displayed in
      relation to two reference frames that move relative to each other, so that
      different temporal orders are described in each reference frame. As applied to
      spatial span, a sequence of dots was displayed on a rectangular template that
      moved relative to the computer screen and the observer. Three experiments showed
      that the choice of reference frame is influenced by prior conditions, the size of
      the template, and the presence of an alternative stationary reference frame.
      Recall was impaired (1) when the template moved, suggesting that movement
      interference occurred, and (2) with increasing template size, but only if the
      template was used as the reference frame.

PMID- 18717393
TI  - Distractor inhibition is more effective at a central than at a peripheral
      location.
AB  - The "distractor eccentricity effect" refers to the finding of reduced
      interference from an incompatible distractor at a central relative to a
      peripheral location (Chen, 2008). The present study examines the mechanism that
      underlies the distractor eccentricity effect, and relates it to the inattentional
      blindness explored by Mack and Rock (1998), which was also more marked at a
      foveal than at a parafoveal location. The results suggest that these two visual
      phenomena may reflect the same underlying mechanism--a gradient of increasing
      attentional suppression from the periphery to the center.

PMID- 18717394
TI  - Perceptual asynchronies between color and motion at the onset of motion and along
      the motion trajectory.
AB  - A color change that is physically simultaneous with the onset of object motion
      may be perceived as occurring before the initial displacement. In contrast, a
      colored flash during object motion is displaced in the direction of motion,
      suggesting that it is perceived after the continuous position change. The aim of
      our study was to reconcile these apparently conflicting results. To this end, we
      reexamined color-motion asynchronies as a function of trajectory position. Our
      results indicate that an abrupt color change lags object motion along the
      trajectory, but no asynchrony was found when the abrupt color change occurred at
      motion onset. Even if the lag of color relative to motion decreased with
      increasing object size, we did not replicate a lag of motion relative to color in
      any of our experiments. Furthermore, judgments at motion onset were not
      correlated with judgments along the trajectory, suggesting that the underlying
      mechanisms or task demands were different. Temporal order may be judged at motion
      onset, whereas position is judged during ongoing motion.

PMID- 18717395
TI  - Backward recognition masking as a general type of interference in needed
      poststimulus processing.
AB  - Auditory backward recognition masking (ABRM) has been argued to reflect
      interference in the storage and/or processing of a short-lived sensory form of
      information and has been viewed as a relatively invariant attribute of auditory
      pitch processing for very brief stimuli that are minimally separated in frequency
      (DeltaF). In contrast, the present study demonstrates that ABRM reflects
      interference with several basic principles of auditory processing. Measured in
      terms of target tone duration, rather than DeltaF, ABRM is demonstrated for
      target stimuli representing the interval of a musical fifth and masker-target
      stimulus intervals of a musical third, with thresholds ranging from approximately
      22 to 55 msec and psychometric functions that are indicative of more than one
      contributing factor. On the basis of common underlying principles, the
      possibility that the threshold for the identification of temporal order of onset
      reflects ABRM and possible implications for the perception of complex stimuli,
      including speech, are discussed.

PMID- 18717396
TI  - Perceptual learning and the visual control of braking.
AB  - Performance on a visually guided action may improve with practice because
      observers become perceptually attuned to more reliable optical information. Fajen
      and Devaney (2006) investigated perceptual attunement, using an emergency braking
      task in which subjects waited until the last possible moment before slamming on
      the brakes. The subjects in that study learned to use more reliable optical
      variables with practice, allowing them to perform the task more successfully
      across changes in the size of the approached object and the speed of approach. In
      Experiment 1 of the present study, subjects completed blocks of normal, regulated
      braking before and after practice on emergency braking. Size and speed effects
      that were present at early stages diminished or were eliminated after practice,
      suggesting that perceptual attunement resulting from practice on emergency
      braking transfers to normal, regulated braking. In Experiment 2, practice on
      regulated braking alone also resulted in perceptual attunement. The findings
      suggest that braking is not always guided on the basis of an optical invariant
      and that perceptual attunement plays an important role in learning to perform a
      visually guided action.

PMID- 18717397
TI  - Practice in visual search produces decreased capacity demands but increased
      distraction.
AB  - Lavie (1995) proposed a load account of selective attention, which holds that
      spare capacity is involuntarily allocated to the processing of irrelevant
      stimuli. In support of this account, Lavie and Cox (1997) combined a letter
      search task with a flanker task and found that increasing load (search set size)
      resulted in decreased interference from an irrelevant distractor letter. In three
      experiments using a very similar procedure, we varied distractor location and
      distractor distinctiveness and observed that as load increased (from set size 2
      to set size 6), there was a consistent reduction in interference. Critically, we
      addressed a fundamental hypothesis derived from the load account-that practice
      reduces capacity demands. This hypothesis leads to the rather counterintuitive
      prediction that as performance improves with practice, distractor processing
      should actually increase. Indeed, we found that interference in a high-load
      condition (set size 6), but not in a low-load condition (set size 2), did
      increase with practice. We describe a two-stage dilution account of attention
      that accommodates these results.

PMID- 18717398
TI  - Prepare for the new insurance game: "evidence-based" dental plans.

PMID- 18717399
TI  - Liners, bases, and cements: an in-depth review, Part 2.

PMID- 18717400
TI  - Bite force and masticatory efficiency in implant-retained dentures: literature
      review.

PMID- 18717401
TI  - Neuromuscular dentistry.

PMID- 18717402
TI  - The role of an Er,Cr:YSGG laser in the placement of immediate molar implants:
      scientific and clinical rationale.

PMID- 18717403
TI  - Creating the ideal prosthodontic platform: implants or endodontics in the
      aesthetic zone?

PMID- 18717404
TI  - Implants in the 21st century--computer guided surgery.

PMID- 18717405
TI  - Atraumatic extractions: a biomechanical rationale.
AB  - Biomechanical aspects of force have been applied to tooth extraction for
      centuries. However, the mechanical advantages available to extract the teeth were
      primarily applied to hold the crown of the tooth, rather than help extract it. An
      extraction device (Physics Forceps) has been developed to apply a biomechanical
      rationale to the extraction process of a tooth using a class 1 lever, creep, and
      shear components of force.

PMID- 18717406
TI  - Minimally invasive dentistry combined with laser gingival plastic surgery:
      maximize your aesthetic results.

PMID- 18717407
TI  - The EndoVac method of endodontic irrigation, Part 3: System components and their
      interaction.

PMID- 18717409
TI  - Developing a comprehensive life plan, Part 1; The life cycle of a dentist.

PMID- 18717408
TI  - Bipolar electrosurgery: gingival modification in passive eruption cases.

PMID- 18717410
TI  - Doctor, why wasn't I told this before?

PMID- 18717411
TI  - Digital photography and your laboratory.

PMID- 18717412
TI  - Celebrating the 25th anniversary of the operating microscope in dentistry.

PMID- 18717413
TI  - A changing landscape.

PMID- 18717414
TI  - It doesn't pay to play the percentages.

PMID- 18717415
TI  - RN embraced culture in her role on First Nations community.

PMID- 18717417
TI  - One thing isn't so hard.

PMID- 18717416
TI  - Hiker remembers rescue. Interview by Rose Mary Phillip.

PMID- 18717419
TI  - Working towards harmony in RN regulation.

PMID- 18717420
TI  - New era of preventing birth-related deaths. Best practices target consistency,
      communication and technology. Interview by Alan Joch.

PMID- 18717421
TI  - Curbing hospital-acquired infections. Hand hygiene compliance remains a goal
      unrealized.

PMID- 18717422
TI  - Synchronization. Standards in motion.

PMID- 18717423
TI  - Mobile systems make the rounds.

PMID- 18717424
TI  - 2008 Most Wired Supply Chain Innovator Awards.

PMID- 18717425
TI  - How to solve wet packs, and evaluate water issues.

PMID- 18717426
TI  - Multifaceted printer saves nurses time.

PMID- 18717427
TI  - TDA historical perspectives: dentists, dental hygienists, and the dental team.

PMID- 18717428
TI  - The 2007 C. T. Rowland Award orthodontic case report.

PMID- 18717429
TI  - Tooth whitening: a clinical review.

PMID- 18717430
TI  - Oral and maxillofacial pathology case of the month. Verrucous carcinoma.

PMID- 18717431
TI  - Teaching and assessing competency in retinal lasers in ophthalmology residency.
AB  - BACKGROUND AND OBJECTIVE: The Accreditation Council for Graduate Medical
      Education has mandated that residency programs teach and assess six specific
      competencies (ie, medical knowledge, patient care, communication and
      interpersonal skills, professionalism, practice-based learning, and systems-based
      learning). To the authors' knowledge, there is no standardized and widely used
      curriculum for teaching and assessing resident competencies in retinal lasers.
      METHODS: The pertinent literature on resident education in retinal lasers is
      reviewed and specific "good practices" for teaching and assessing laser
      competency are presented. RESULTS: Development and deployment of educational
      tools that teach and assess laser competency simultaneously; are reliable,
      reproducible, and valid; have low faculty time burden; and are affordable,
      generalizable, and fair are recommended. CONCLUSION: Retinal laser competency can
      be taught and assessed in ophthalmology residency training programs. Future
      research will be needed to provide evidence that these teaching and assessment
      tools produce improved educational and patient outcomes and provide verifiable,
      reliable, and valid evidence of resident competence in retinal lasers.

PMID- 18717432
TI  - Relationship between central corneal thickness and hypotony-related complications
      after glaucoma surgery.
AB  - BACKGROUND AND OBJECTIVE: To examine the hypothesis that patients with increased
      central corneal thickness may have an overestimation of Goldmann applanation
      tension and a predisposition to hypotony-related complications. PATIENTS AND
      METHODS: A case-control analysis of patients with an intraocular pressure of 7 mm
      Hg or less on two consecutive postoperative visits following glaucoma filtration
      or drainage implant surgery was performed. Forward stepwise multiple logistic
      regression was used to determine the model that best predicted hypotony-related
      complications defined as choroidal effusion or hypotony maculopathy. RESULTS:
      Forty-three eyes (17 with hypotony-related complications and 26 controls) of 43
      patients were enrolled. Eyes with pseudophakia (P = .006) and lower postoperative
      intraocular pressure (P = .013) were significantly more likely to develop
      hypotony-related complications. Mean central corneal thickness was similar in
      eyes with hypotony-related complications (519 +/- 32 microm) and controls (525 +/
      37 microm) and was not a significant predictor of hypotony-related complications
      in the multivariate model (P = .90). CONCLUSION: Increased central corneal
      thickness does not represent a risk factor for hypotony-related complications
      following glaucoma surgery.

PMID- 18717433
TI  - Macular holes associated with diabetic tractional retinal detachments.
AB  - BACKGROUND AND OBJECTIVE: Evaluation of surgical treatment of full-thickness
      macular holes secondary to diabetic tractional retinal detachments was conducted.
      PATIENTS AND METHODS: A retrospective review of medical records, fluorescein
      angiograms, fundus photographs, optical coherence tomography images, and
      operative findings of six consecutive patients with full-thickness macular holes
      and diabetic tractional retinal detachments was completed. Each eye was treated
      with pars plana vitrectomy, tractional retinal detachment repair, membranectomy,
      indocyanine green-assisted internal limiting membrane peeling, and intraocular
      gas tamponade. RESULTS: Surgical intervention resulted in the closure of all full
      thickness macular holes. Mean best-corrected visual acuity was 20/250
      preoperatively and 20/100 postoperatively, with all patients having improvement
      after a mean follow-up of 10 months. CONCLUSION: Closure of tractional retinal
      detachments related to full-thickness macular holes can be achieved via pars
      plana vitrectomy, complete membranectomy, and intraocular gas. Vitrectomy with
      dissection of proliferative membranes helps to relieve the tractional forces
      responsible for full-thickness macular hole formation, enabling successful
      closure of the diabetic full-thickness macular holes and resulting in visual
      acuity improvement.

PMID- 18717434
TI  - Treatment of neovascular age-related macular degeneration with pegaptanib and
      boosting with bevacizumab or ranibizumab as needed.
AB  - BACKGROUND AND OBJECTIVE: Neovascular age-related macular degeneration presents a
      therapeutic challenge. The efficacy of pegaptanib sodium, a selective inhibitor
      of vascular endothelial growth factor 165, was examined as a therapeutic mainstay
      combined with "as needed" boosts of nonselective vascular endothelial growth
      factor blockade with bevacizumab or ranibizumab. PATIENTS AND METHODS: A
      retrospective chart review of outcomes of patients treated with pegaptanib and
      later boosted with bevacizumab or ranibizumab was conducted. Visual acuity,
      optical coherence tomography, and fluorescein angiography findings were recorded
      and assessed. RESULTS: During a mean follow-up of 12.1 months, an average of 7.8
      injections of pegaptanib 0.3 mg, 1.4 injections of bevacizumab 1.25 mg, and 0.9
      injections of ranibizumab 0.5 mg were administered to 17 eyes. In all, 47% of
      eyes gained 3 or more lines of visual acuity and 76% gained 0 or more lines.
      CONCLUSION: Pegaptanib as a mainstay of neovascular age-related macular
      degeneration therapy with an occasional boost of bevacizumab or ranibizumab
      appears to be an effective treatment option.

PMID- 18717435
TI  - Intra-observer and inter-observer reliability and reproducibility of slit-lamp
      adapted optical coherence tomography for evaluation of anterior chamber depth and
      central corneal thickness.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the intra-observer and inter-observer
      reproducibility of anterior chamber depth (ACD) and central corneal thickness
      (CCT) measurements taken by slit-lamp-adapted optical coherence tomography (SL
      OCT) and to evaluate concordance of CCT and ACD values obtained by SL-OCT with
      gold standard devices. PATIENTS AND METHODS: Three images of each eye were taken
      by two different operators using SL-OCT. ACD and CCT values obtained by each
      operator were determined and compared to one another and to ultrasonic pachymetry
      (CCT) and axial OCT biometry (ACD) values obtained by a third, masked operator.
      Intra-observer and inter-operator reproducibility was assessed using the
      intraclass correlation coefficient (ICC). RESULTS: Forty-one eyes of healthy
      subjects were enrolled. Mean CCT was 0.556 +/- 0.020, 0.557 +/- 0.019, and 0.532
      +/- 0.032 and mean ACD was 3.12 +/- 0.36, 3.13 +/- 0.38, and 3.50 +/- 0.44 for
      operators 1, 2, and 3, respectively (P < .001, for both CCT and ACD). Intra
      operator reproducibility for CCT (ICC of 0.948 to 0.995) and ACD (ICC of 0.972 to
      0.987) was excellent. CONCLUSION: SL-OCT provides highly reproducible measures
      for both CCT and ACD. SL-OCT yields higher values for CCT compared to ultrasonic
      pachymetry and lower values for ACD compared to axial OCT biometry. Caution
      should be taken when extrapolating these data into clinical practice until the
      differences between SL-OCT, axial OCT biometry, and ultrasonic pachymetry can be
      further elucidated.

PMID- 18717436
TI  - Ultrawide angle fluorescein angiographic imaging: a comparison to conventional
      digital acquisition systems.
AB  - BACKGROUND AND OBJECTIVE: A prototype ultrawide field angiographic system and
      conventional technology were compared. PATIENTS AND METHODS: Thirty subjects with
      diabetic retinopathy were imaged in three centers by conventional (Topcon Inc.,
      Paramus, NJ, or Carl Zeiss Meditec, Dublin, CA) and ultrawide field (Optos P200A;
      Optos Inc., Dunfermline, Scotland) digital fluorescein angiography units. A
      calibrated grid was digitally placed on the images to facilitate measurements.
      Main outcome measures were field of view and the number of grid sectors
      displaying retinal ischemia and neovascularization. Secondary measures were image
      quality and patient satisfaction scores. RESULTS: The P200A provided a
      significantly greater visual field extent of 8.7 +/- 1.6 disc diameters (DD)
      compared to the conventional systems (3.4 +/- 0.76 DD) (P < .001). Retinal
      ischemia was better revealed (16.9 +/- 15 vs 3.4 +/- 4.26 sectors) with the
      prototype, but image quality was superior with the conventional system. Patient
      satisfaction scores did not differ between systems. CONCLUSION: A prototype
      ultrawide angle imaging system displayed significantly more diabetic retinal
      pathology in a single image than conventional systems.

PMID- 18717437
TI  - In vivo laser confocal microscopy findings of cryopreserved and fresh human
      amniotic membrane.
AB  - BACKGROUND AND OBJECTIVE: Recently, the cornea-specific in vivo laser confocal
      microscope has become available. The objective of the current study was to obtain
      laser confocal images of fresh and cryopreserved human amniotic membrane.
      MATERIALS AND METHODS: Fresh and cryopreserved amniotic membranes from different
      donors were examined using the in vivo laser scanning confocal microscope
      (Heidelberg Retina Tomograph II Rostock Cornea Module [HRT II-RCM]; Heidelberg
      Engineering GmbH, Dossenheim, Germany). RESULTS: In all samples of both fresh and
      cryopreserved amniotic membranes, the HRT II-RCM resolved four distinct layers:
      the epithelium, a basement membrane, a cell-rich stromal layer (fibroblast
      layer), and a spongy stromal layer. In a posterior aspect of the basement
      membrane layer (facing the fibroblast layer), microfolds were more prominent in
      fresh amniotic membranes than in cryopreserved amniotic membranes. For the cell
      rich stromal layer, mesenchymal cells were observed more distinctively in fresh
      amniotic membranes than in cryopreserved amniotic membranes. CONCLUSION: These
      baseline laser confocal images can be used for future investigation of in vivo
      remodeling after amniotic membrane transplantation.

PMID- 18717438
TI  - Lack of toxicity during long-term follow-up of intraocular metallic fragments
      after pars plana vitrectomy.
AB  - A 45-year-old woman underwent pars plana vitrectomy for vitreous hemorrhage in
      the right eye 20 years prior to presentation. She also had prior
      phacoemulsification and intraocular lens implantation and subsequent laser
      capsulotomy in the right eye. Multiple preretinal metallic fragments were visible
      on the retinal surface and were presumed to be stainless steel fragments from the
      vitrectomy instrument. The fragments were documented by color photography,
      fluorescein angiography, optical coherence tomography, and echography. Visual
      acuity was 20/30, electrophysiologic testing was normal, and no signs of toxicity
      were present. No surgical intervention was planned.

PMID- 18717439
TI  - Suprachoroidal hemorrhage caused by breakage of a 25-gauge cannula.
AB  - A 72-year-old woman had vitreous surgery for epiretinal membrane using the 25
      gauge vitrectomy system. During the removal of the cannula at the end of the
      surgery, half of its tip was noted to be missing. The following day, a severe
      choroidal detachment associated with a hypotony was found. A second surgery was
      performed, including drainage of suprachoroidal hemorrhage and choroidal fluid
      and the removal of the tip of the 25-gauge cannula stuck inside the sclerotomy.
      The retained cannula tip might have acted as a channel allowing vitreous fluid
      into the suprachoroidal space, resulting in choroidal detachment, hemorrhage, and
      hypotony.

PMID- 18717440
TI  - Vitrectomy and translocation of the anterior chamber intraocular lens to the
      sulcus: a closed microsurgical technique for the UGH syndrome.
AB  - This interventional case report presents an anterior chamber intraocular lens (AC
      IOL) translocation technique to manage a case of uveitis-glaucoma-hyphema (UGH)
      syndrome associated with posterior dislocation of nuclear fragments and vitreitis
      as a consequence of capsule rupture during cataract surgery. Pars plana
      vitrectomy followed by an AC-IOL translocation from the anterior chamber to the
      sulcus without additional surgical corneal incision was performed. At 12 months'
      follow-up, the original AC-IOL was in stable position in the posterior chamber,
      with binocular refractive balance and no further astigmatism and resolution of
      the UGH syndrome.

PMID- 18717441
TI  - Endocapsular cellulomonas as a cause of persistent postoperative endophthalmitis.
AB  - Sequestration of bacteria within the capsular fornices after cataract extraction
      with intraocular lens implantation can cause both acute and chronic inflammation.
      A case of persistent postoperative endophthalmitis caused by capsular
      sequestration of Cellulomonas is described. The patient underwent uncomplicated
      cataract extraction with intraocular lens implantation and subsequently developed
      acute postoperative endophthalmitis. Inflammation persisted despite several
      vitreous taps and the injection of intravitreal antibiotics. Definitive treatment
      required pars plana vitrectomy, intraocular lens explantation, capsular bag
      removal, and intravitreal and parenteral antibiotics. In patients with
      postoperative endophthalmitis, one must consider atypical organisms as the source
      and should consider explantation of the intraocular lens with capsular bag
      removal.

PMID- 18717442
TI  - Rapid onset proptosis and vision loss as the initial presentation of Burkitt
      lymphoma.
AB  - Burkitt lymphoma is a rapidly growing, high-grade non-Hodgkin lymphoma occurring
      in three distinct clinical subtypes: endemic, sporadic, and human
      immunodeficiency associated. The sporadic subtype typically presents as an
      abdominal mass. Orbital involvement has rarely been reported. The authors report
      a case of Burkitt lymphoma presenting as rapidly progressive proptosis and loss
      of vision. Given the tumor's rapid growth rate, potential for vision loss, and
      good response to chemotherapy, clinicians should be aware of this rare
      presentation.

PMID- 18717443
TI  - Scleral fixation of a silicone plate haptic intraocular lens in a patient showing
      repeated pupillary intraocular lens capture.
AB  - A 39-year-old man with Marfan syndrome underwent scleral fixation using a three
      piece foldable intraocular lens and experienced repeated pupillary intraocular
      lens captures secondary to a pliable iris. As a result, the patient needed an
      additional pupilloplasty. In the opposite eye, a silicone plate haptic
      intraocular lens was used for scleral fixation because it was thought that the
      plate design could prevent pupillary intraocular lens capture, even in cases
      involving a pliable iris. At the 27-month follow-up examination, the patient
      showed good centration of the intraocular lens in the eye that used the silicone
      plate haptic intraocular lens without pupillary intraocular lens capture.

PMID- 18717444
TI  - Progressive optic neuropathy in congenital glaucoma associated with the Sirsasana
      yoga posture.
AB  - The authors describe a case of progressive optic neuropathy in a patient with
      congenital glaucoma who had routinely practiced the Sirsasana (headstand) yoga
      posture for several years. Ophthalmic examination included best-corrected visual
      acuity, anterior segment examination, indirect ophthalmoscopy, ultrasound
      pachymetry for central corneal thickness, and intraocular pressure before,
      during, and after maintaining the Sirsasana posture for 5 minutes. Intraocular
      pressure increased significantly during the Sirsasana posture. Transient
      elevation in intraocular pressure during yoga exercises may lead to progressive
      glaucomatous optic neuropathy, especially in susceptible patients with congenital
      glaucoma.

PMID- 18717445
TI  - Oral niacin can increase intraocular pressure.
AB  - The intraocular pressure of a 73-year-old man with a history of primary open
      angle glaucoma had been approximately 21 and 17 mm Hg in the right and left eyes,
      respectively, while taking latanoprost 0.005% and dorzolamide hydrochloride 2%.
      When taking 500 mg of oral niacin (also known as vitamin B3 or nicotinic acid),
      his intraocular pressure increased to 37 and 27 mm Hg in the right and left eyes,
      respectively, on one occasion. On reexamination, the intraocular pressure had
      increased to 28 and 23 mm Hg in the right and left eyes, respectively. Each time
      the niacin was stopped, the intraocular pressure decreased to the original
      levels.

PMID- 18717446
TI  - Diode laser transscleral cyclophotocoagulation-induced staphyloma following
      trabeculectomy with mitomycin C.
AB  - A 42-year-old man developed progressive scleral iatrogenic staphyloma in the
      region of a previous trabeculectomy with mitomycin C after three sessions of
      diode laser transscleral cyclophotocoagulation for a refractory glaucoma
      secondary to trauma. After clinical and laboratory evaluations, no signs of
      systemic or autoimmune disorders were found. The patient underwent a
      reinforcement of the eye wall with a scleral patch over the staphyloma area and a
      glaucoma drainage device was implanted. Repeated transscleral
      cyclophotocoagulation procedures should be performed cautiously in patients who
      have had previous trabeculectomy.

PMID- 18717447
TI  - Repair of anterior staphyloma with dehydrated dura mater patch graft.
AB  - A case of postoperative large anterior staphyloma of the sclera was treated with
      a dehydrated cadaveric dura mater patch graft. Structural integrity of the globe
      and a good cosmetic result were obtained after the surgery. During the follow-up
      of 2 years, no recurrence of staphyloma developed.

PMID- 18717448
TI  - Regression of vasoproliferative tumor with systemic infliximab.
AB  - The anti-tumor necrosis factor (TNF) monoclonal antibody infliximab inhibits the
      pleiotropic actions of TNF and is widely used for the treatment of inflammatory
      diseases, such as uveitis. A pathogenetic role of TNF in ocular inflammatory
      conditions has recently emerged. The authors describe a patient with collagen
      mixed disease who had decreased vision in the left eye. Fundus examination
      disclosed bilateral peripheral vasoproliferative tumors and macular edema in the
      left eye. The patient underwent treatment with infliximab intravenously for his
      systemic condition. Regression of the vasoproliferative tumors in both eyes and
      improvement of macular edema in the left eye was observed. Although the data are
      limited, anti-TNF antibodies such as infliximab may be useful in the treatment of
      retinal vascular tumors.

PMID- 18717449
TI  - Laser treatment for retinopathy of prematurity through the incubator wall.
AB  - In this era of early treatment for retinopathy of prematurity, sick infants who
      develop aggressive diseases or remain oxygen and temperature dependent may be
      treated while they are inside the incubator itself, thus avoiding unnecessary
      delays. This article describes the treatment of eight infants with retinopathy of
      prematurity who were dependent on an incubator by using a laser indirect
      ophthalmoscope delivery system through the slanting transparent wall of the
      incubator. In this series, which is the largest to date, the relative advantages
      and disadvantages of the procedure are discussed.

PMID- 18717450
TI  - [Need for clinical guidelines for chronic periodontitis in general and
      specialized Belgian practice].
AB  - As the prevalence of periodontitis is more than 40 % in the adult Belgian
      population, periodontists are clearly understaffed to treat this disease in all
      patients. Therefore, it seems logic that mild forms of chronic periodontitis are
      treated by the general practitioner especially because Belgium lacks dental
      hygienists. Important prerequisites for organizing periodontal care as such
      relate to the general practitioner who should use the same techniques, have
      comparable communicative skills to motivate patients and create a similar amount
      of time for periodontal treatment as the specialist. After all, the patient has
      the right to qualitative treatment regardless of the level of education of the
      care provider. In order to guarantee this in general practice as much as
      possible, there is a need for clinical guidelines developed by specialists. These
      guidelines should not only support the general practitioner in treating disease;
      above all, they should assist the dentist in periodontal diagnosis. Hitherto,
      periodontal screening by general dentists seems to be infrequently performed even
      though reimbursement of the Dutch Periodontal Screening Index is implemented in
      the Belgian healthcare security system. In this manuscript possible explanations
      for this phenomenon are discussed. Apart from the need for guidelines in general
      practice, guidelines for surgical treatment seem compulsory to uniform treatment
      protocols in specialized practice. Extreme variation in the recommendation of
      surgery among Belgian specialists calls for consensus statements.

PMID- 18717451
TI  - [The development of clinical guidelines for the diagnosis and treatment of
      chronic periodontitis in Belgium].
AB  - In many disciplines of medicine guidelines are developed for the diagnosis and
      treatment of disease. These are essentially intended to standardize care and to
      optimize communication between the general practitioner and the specialist.
      Guidelines have already been described in the literature for chronic
      periodontitis. However, given the unique conditions in Belgium, these may not be
      appropriate for the average dental practice. In this manuscript the development
      of Belgian clinical guidelines for the diagnosis and treatment of chronic
      periodontitis is described. Basically, ten clinical questions were used as a
      basis for a thorough literature search. Evidence-based clinical guidelines were
      developed and adapted during three peer review sessions. In the final session
      Belgian specialists, who had all been invited, participated. This made sure that
      the scientific input was sufficiently transformed into clinical guidelines which
      are actually feasible today in Belgium.

PMID- 18717452
TI  - [Guidelines for periodontal diagnosis in Belgium].
AB  - Proper examination of patients is essential in assessing treatment needs. This
      includes at least a thorough anamnesis and clinical examination. As periodontal
      diseases are highly-prevalent in Belgium, every patient should be examined as
      such on a routine basis in general practice. After all, early detection of
      pathology avoids extensive periodontal therapy and favours tooth retention in the
      end, which is the ultimate goal. This manuscript offers the clinician, in
      particular the general practitioner, a number of guidelines in reference to
      periodontal diagnosis.

PMID- 18717453
TI  - [Guidelines in reference to the use of supplementary diagnostic tests for chronic
      periodontitis in Belgium].
AB  - The need and development of clinical guidelines for the diagnosis and treatment
      of chronic periodontitis in Belgium has been previously described. The use of
      supplementary diagnostic tests in this field is widespread. The question is
      whether the existing scientific evidence justifies the routine use of these tests
      in the diagnosis of chronic periodontitis. A thorough search of the literature
      was conducted in reference to microbiological testing as well as genetic testing
      for periodontitis.

PMID- 18717455
TI  - [In the beginning was a relationship].
AB  - Judgment and actions based on scientific evidence are modified by the unique
      caregiver-patient relationship. Caregivers relying exclusively upon "rational"
      decisions in line with evidence-based clinical recommendations avoid their
      relational responsibility. The "noble" purpose illustrates that decisions to
      treat can be at the same time pointless and valuable. Dia (through) - logue
      (knowledge) makes it possible to go beyond informed consent, which holds
      caregivers responsible for providing information and patients for the decision to
      treat. Finally, where healing is no longer achievable and autonomy dies away,
      compassion rather than therapeutic tenacity might be the answer. These examples
      are explained corresponding to the philosophical ideas of respectively Emmanuel
      Levinas en Roger Burgraeve (noble purpose), Martin Buber (dialogical thinking)
      and Daniel C. Dennett (autonomy loss).

PMID- 18717454
TI  - [A 24 month evaluation of zinc oxide pulpotomy on primary canines].
AB  - Pulpotomy is the most performed and controversial therapeutic in pediatric
      dentistry. Since formocresol is known to have a toxic effect on living tissues,
      plus a mutagenic and carcinogenic potential with a systemic uptake of formocresol
      via pulpotomized teeth, other alternative products have been investigated. Twenty
      five decayed primary canines and twenty-five healthy primary canines
      necessitating disking for orthodontic purposes were pulpotomized using non
      modified Zinc Oxide Eugenol. The effects of this material were evaluated both
      clinically and radiographically. Post operative control examinations were
      performed at 1, 6, 12, and 24 months trying to detect spontaneous or stimulated
      pain, pathological tooth mobility, abscesses or fistulas, internal or external
      pathological tooth resorption, periapical bone destruction, or canal
      obliteration. Pain was absent at 24 months post operatively. Half of the treated
      canines presented with a mobility, while internal and external resorptions were
      more frequent in decayed teeth and their number increased with time. On the other
      hand, abscesses and fistulas were equally found in both treated groups. The
      observations were compared to others related to formocresol ferric sulfate, MTA,
      and laser pulpotomies, using the binominal law, or the comparative test of an
      observed proportion to a reference proportion. In this study, and based on the
      excessive negative results in both groups, we demonstrated that non fixative
      pulpotomies on temporary canines were not a promising technique.

PMID- 18717456
TI  - [Macro- and microhematuria in the adult].

PMID- 18717457
TI  - [Possible triggers of decompensated chronic complex tinnitus with a therapeutic
      approach as relating to treatment of epilepsy].
AB  - Coxsackieviruses are responsible for numerable diseases in man. This is also the
      reason for the high prevalence of endemic infection rates in the population. Our
      analysis (working hypothesis) will focus on the participation of Coxsackieviruses
      in chronic decompensated, complex tinnitus. Examination of the Coxsackievirus
      antibody titers might reveal the extent to which a Coxsackieviruses-triggered
      disease of the central nervous system participates in the direct sequelae of
      tinnitus disorders. A spread of Coxsackieviruses to the auditory pathway might
      lead to an overstimulation of the auditory pathway, comparable to an epileptic
      lesion. Based on this assumption, treatment with an antiepileptic would make
      sense. The reasoning behind this working hypothesis is to find a potentially new
      diagnostic and therapeutic roadmap as a further guide for specialized clinics.
      The authors are well aware that previous results bear little relevance as they
      have been based on small case numbers.

PMID- 18717459
TI  - [Ascites].
AB  - Ascites means accumulation of fluid within the peritoneal cavity, usually in
      patients with cirrhosis. Diagnostic paracentesis (cell count, albumin, cell
      culture) is a must. Na-restriction remains the cornerstone of treatment (< 3 g
      NaCl/d). Spironolactone is the drug of choice, in some patients in addition with
      proximally acting diuretics. Minimum effective dosage is recommented to reduce
      side-effects. Pronounced ascites can be treated by large-volume paracentesis with
      concomitant albumin-infusion. Only very few patients suffer from refractory
      ascites. TIPS is a treatment modality for this group. However, TIPS may
      precipitate PSE in some patients with decompensated liver cirrhosis.

PMID- 18717460
TI  - [Identification of risk factors (the method of logistic regression)].
AB  - Logistic regression is a model used for prediction of an event (e.g. heart
      attack: yes/no) using several predictor variables whereas the output is confined
      to values between 0 and 1. The regression coefficients describe the size of the
      contribution of the risk factor. In this short introduction an example is used to
      explain the basic principle and the advantages of the logistic regression.

PMID- 18717461
TI  - [Otalgia].

PMID- 18717462
TI  - [Pain of the musculoskeletal system of unknown origin in immigrants. Vitamin D3
      deficiency caused by insufficient exposure of the skin to sunlight].
AB  - We present two patients with vitamin D3 deficiency caused by insufficient
      exposure of the skin to sunlight. The deficiency was due to the dark pigmentation
      of the skin in the first case and caused by constant wearing of veil and all
      covering clothes as well as by insufficient exposure to sunlight in the second
      case. Both patients developed osteomalacia with musculoskeletal problems; they
      had typical laboratory test results (elevated alkaline phosphatase and serum
      calcium in the low normal range) and radiologically evident, non-dislocated
      fractures (insufficiency fractures). Treatment with vitamin D3 led in both cases
      to sustained relief of pain.

PMID- 18717463
TI  - [Compliance--adherence--concordance--persistence].

PMID- 18717464
TI  - We can solve the construction safety crisis.

PMID- 18717465
TI  - The criticality of near misses.

PMID- 18717466
TI  - Step change from the bottom up.

PMID- 18717467
TI  - Arc protection around the world.

PMID- 18717468
TI  - Helping workers protect themselves.

PMID- 18717469
TI  - When communicating saves lives.

PMID- 18717470
TI  - Leading safety and the Hispanic workforce.

PMID- 18717471
TI  - A call for leadership.

PMID- 18717472
TI  - Wash and wear.

PMID- 18717474
TI  - The lessons of Charleston.

PMID- 18717473
TI  - The right gloves are out there.

PMID- 18717475
TI  - Fire protection in mission critical facilities.

PMID- 18717476
TI  - Trash talk.

PMID- 18717477
TI  - Case report: carotid artery calcifications appearing on panoramic radiographs.

PMID- 18717478
TI  - TMD symptoms ... A practical approach to evaluate & treat.

PMID- 18717479
TI  - What you should know about buy-sell agreements.

PMID- 18717480
TI  - Dendrimers and their pharmaceutical applications--a review.
AB  - Dendrimers are hyperbranched macromolecules having tree like structure,
      consisting of a core molecule and alternating layers of monomers. They can be
      synthesized by divergent and convergent growth methods. During synthesis,
      properties like dendrimer size, molecular mass, surface group can be controlled
      and configured to the desired need. The ability of dendrimers to encapsulate and
      bind the guest molecule can be used for solubility enhancement, sustained release
      and drug delivery applications. In this review we tried to delineate the
      properties, synthesis methods and expound potential pharmaceutical applications
      along with toxicological considerations of dendrimers.

PMID- 18717481
TI  - Novel oxazole containing phenylpropane derivatives as peroxisome proliferator
      activated receptor agonists with hypolipidemic activity.
AB  - alpha-Alkoxy arylpropanoic acids containing 2-phenyloxazole-4yl-alkyl moiety are
      found to be potent hypolipidemic agents. These compounds were potent activators
      of the peroxisome proliferator activated receptor gamma (PPARgamma), with
      moderate PPARalpha activity and known to cause adverse effects such as weight
      gain and edema, which are essentially attributed to PPARgamma activation.
      Although extensive work has been done on the phenylpropanoic acid class of
      compounds, other phenyl propane derivatives such as alcohols, amines, ethers etc.
      have not received much attention. In order to develop predominant PPARalpha
      agonists as hypolipidemic agents with minor chemical modifications on compound
      III, we have synthesised few (2S)-ethoxyphenylpropane derivatives containing a 2
      phenyl-5-methyloxazole-4ylalkoxy moiety of the general formula IV and evaluated
      by PPARalpha and gamma transactivation assay in conjugation with in vivo studies
      in male Swiss albino mice model. Compounds 3c and 3d showed the desired
      predominant PPARalpha activity and excellent tryiglyceride reduction in vivo and
      were selected as lead compounds for further development as hypolipidemic agents.

PMID- 18717482
TI  - Rapid determination of nitazoxanide in tablets using reversed-phase ultra
      performance liquid chromatography (UPLC) and high-performance liquid
      chromatography.
AB  - A simple and rapid determination method for nitazoxanide (NTZ), an antiprotozoal
      agent, was developed using reverse-phase HPLC and Ultra Performance Liquid
      Chromatography (UPLC). Only six minutes gradient condition for NTZ analysis using
      UPLC was achieved. The mobile phase consisted of a mixture of phosphate buffer
      (pH 6.0) and acetonitrile. The repeatability (relative standard deviation (RSD),
      n = 6) and the correlation coefficient from linearity (the range from 80% to 120%
      of amount) were 0.25% and 0.9963 for UPLC and 0.15% and 0.9988 for HPLC,
      respectively. The quantitative values of NTZ in tablets were 103.2% for HPLC and
      98.7% for UPLC. The RSDs of quantitative values of sample solution were
      calculated to be 4.06% to 4.64% for HPLC and 0.15% to 0.36% for UPLC.

PMID- 18717483
TI  - Uniformity of weight test: a non-destructive test compared to the European
      Pharmacopoeia test.
AB  - The test for uniformity of weight as stipulated in the European Pharmacopoeia
      (Ph. Eur) is a complicated and time consuming method. The aim of the present
      project was to prove, that a new method developed in the Pharmacy Department of
      the University Hospital of Heidelberg is in principle equivalent to the Ph. Eur.
      method. Six lots of capsules were produced with a hand operated capsule filling
      machine. They were filled with mannitol and Aerosil. Three lots of capsules
      contained 0.5% Aerosil and the other three lots contained 5% Aerosil. Before
      filling the capsules, the lot specific empty capsule weight was defined in order
      to determine the real weight of contents. According to the Ph. Eur. method and
      our method the filling weight was calculated in two different ways. The results
      of both methods were compared always in relation to the real weight of contents
      of the capsules. The results suggested that the average filling weight of the Ph.
      Eur. method could never be well-defined because there is always substance left in
      the capsules when they are emptied in order to determine the empty weight. These
      findings demonstrated that our approach can be considered at least as good as the
      European Pharmacopoeia method. Furthermore the average filling weight of our
      method was more accurate which raises the question if the Ph. Eur. should be
      revised in this regard.

PMID- 18717484
TI  - Effects of hydroxypropyl-beta-cyclodextrin on the chemical stability and the
      aqueous solubility of thalidomide enantiomers.
AB  - The aim of this work was to study the effect of hydroxypropyl-beta-cyclodextrin
      on the solubility and stability of thalidomide enantiomers in aqueous solutions
      for clinical oral administration to be used in HIV-infected children. For this
      reason racemic thalidomide was added to solutions containing different
      concentrations of hydroxypropyl-beta-cyclodextrin. True complexes were obtained
      by using hydroxypropyl-beta-cyclodextrin and the solubility of both thalidomide
      enantiomers was increased directly depending on the amount of hydroxylpropyl-beta
      cyclodextrin in the medium although no enantioselective differences were observed
      at 37 degrees C. The chemical stability of thalidomide enantiomers is clearly
      improved by hydroxypropyl-beta-cyclodextrin. No enantioselective degradation of
      thalidomide was observed in sodium chloride solution (0.9%) samples stored at 6
      degrees C for nine days when hydroxypropyl-beta-cyclodextrin was employed as
      excipient. Therefore a thalidomide solution suitable for oral administration can
      be prepared by adding hydroxypropyl-beta-cyclodextrin at 10% (w/v).

PMID- 18717485
TI  - Pretreatment of pigments to prepare liquids for enteric coating.
AB  - Film coating fluids commonly contain different pigments. The objective of this
      work was a study of the distribution of these particles in the coating film.
      Different pretreatment forms (pigment suspension, pigment paste and untreated
      pigments) were applied. They were incorporated into a Eudragit L 30 D-55
      dispersion. The surface roughness and the mechanical properties of the free films
      indicated, that the most homogeneous film was obtained with the pigment paste.
      The homogeneity of the film was investigated by mechanical testing. The
      protective effect of the coating did not vary with the application of pigments in
      different forms, but the appearance of the coated tablets underwent a
      considerable change.

PMID- 18717486
TI  - Preparation and evaluation of a microemulsion for oral delivery of berberine.
AB  - The principal aim of this study was to develop an oral microemulsion formulation
      of berberine in order to improve its bioavailability. The Microemulsion was
      prepared with pharmaceutically acceptable ingredients such as oleic acid, Tween
      80 and PEG400. Phase diagrams were drawn to elucidate the phase behavior of
      systems, which were composed of Tween 80 as surfactant and PEG400 as
      cosurfactant. A single isotropic region, considered to be a bicontinuous
      microemulsion, was detected in the pseudo ternary phase diagrams. The berberine
      loaded microemulsion was characterized by viscosity, refractive index, electrical
      conductivity and particle size. In vivo pharmacokinetic profile and oral
      bioavailability were also investigated in rats. The optimized formulation was as
      follows: 15 wt.% oleic acid, 17 wt.% Tween-80, 17 wt.% PEG400, and 51 wt.% water.
      The formulated microemulsion was found to be relatively uniform in size (24.0
      nm). The in vivo study indicated that the bioavailability of the oral berberine
      loaded microemulsion formulation was 6.47 times greater than that of the
      berberine tablet suspensions. The results suggest that the microemulsion is a
      promising oral drug delivery system for berberine.

PMID- 18717487
TI  - Pharmacokinetics and excretion of chlorogenic acid in beagle dogs.
AB  - In order to characterize the pharmacokinetics and excretion of chlorogenic acid
      (ChA) in beagle dogs, a gradient high performance liquid chromatographic method
      has been developed and validated for determining ChA concentration in dog serum,
      urine and feces. The pharmacokinetic profile of ChA in dog after an intravenous
      injection was best described by a two-compartment model. Terminal half-lifes were
      similar at dosages of 5, 20 and 50 mg/kg, ranging from 41-45 min, while AUC and
      Cmax values of ChA were dose proportional. There are no differences in Vd and CL
      at three doses of ChA, ranging from 133-252 mL/kg and from 4.4-6.3 mL/min/kg
      respectively. Excretion studies showed that more than 67% ChA was excreted into
      urine and less than 3% ChA was eliminated into feces.

PMID- 18717488
TI  - Development of an in vitro test to determine the water-resistance of sunscreens.
AB  - The aim of this work was to develop an in vitro method for testing the water
      resistance of sun products. For comparison, we used the in vivo method put
      forward by the Colipa. Standards and commercial products were successive baths.
      The Sun protection factor of these different creams was determined in vitro both
      before and after the baths. The result was that two successive baths of 20 min in
      moderately shaken distilled water, at 29 +/- 2 degrees C and may substitute the
      in vivo test.

PMID- 18717489
TI  - Antimultidrug-resistant effect and mechanism of a novel CA-4 analogue MZ3 on
      leukemia cells.
AB  - A major issue in the treatment of leukemia is resistance to chemotherapeutic
      drugs. The most common mechanism encountered in the laboratory is the increased
      efflux of hydrophobic cytotoxic drugs that is mediated by a family of energy
      dependent transporters. Besides, resistance to apoptosis can also cause failure
      in the treatment of leukemia. Recently, we have introduced 4-(4-bromophenyl)-2,3
      dihydro-N,3-bis(3,4,5-trimethoxyphenyl)-2-oxoidmidazole-1-carboxamide (MZ3) as a
      novel synthesized combretastatin A-4 analogue which is a potent and specific
      compound against leukemia cells both in vitro and in vivo. Aim of this study was
      to evaluate the effect of MZ3 on multidrug-resistant (MDR) cancer cells of
      leukemia, and explore the antimultidrug-resistant mechanisms. Here, we observed
      that the MDR leukemia cell models investigated, overexpressing MDR1 (P-gp), were
      hypersensitive against MZ3. Parental K562, HL60 cells and MDR1-overexpressing
      K562R, HL60R cells were employed in this study. MZ3 hypersensitivity was
      confirmed to be based on great apoptosis induction and cell cycle arrest at
      unaltered intracellular drug accumulation. Cell proliferation assay demonstrated
      that, compared with HL60 and K562 cells, HL60R and K562R cells exhibited 1.3-fold
      and 2.4-fold resistance to MZ3, showing 26.9-fold and 92.2-fold resistance to
      daunorubicin (DNR) respectively. Moreover, real-time RT-PCR result showed that
      MZ3 impacted the transcription of MDR1 gene and western blotting results
      indicated that MZ3 can activate apoptosis on MDR cells by downregulating the anti
      apoptotic protein XIAP levels and inducing the decrease in the phosphorylation
      state of ERK. Summarizing, our data demonstrate that MZ3 can inhibit the MDR
      function of leukemia cells, and it exerts the effect through altering the
      transcription of MDR1 genes and downregulating the anti-apopotic protein levels.
      MZ3 may be a potential candidate for further research and development in anti-MDR
      territory.

PMID- 18717490
TI  - Antitumor effects of total alkaloids isolated from Solanum nigrum in vitro and in
      vivo.
AB  - This study demonstrated that the total alkaloids isolated from the traditional
      Chinese medicinal herb Solanum nigrum Linne (SNL-A) inhibited the growth of human
      cervical cancer HeLa cells in culture medium with much lower toxicity to human
      normal lymphocytes. By means of HE staining and TUNEL assay, our results further
      revealed that SNL-A induced cell death by apoptosis. An immunohistochemical assay
      showed down-regulation of the bcl-2 and p53 genes and no obvious change of bax
      gene in the SNL-A treated cells. Subcutaneous injection of HeLa cells induced
      tumor formation in nude mice, and SNL-A showed a significant inhibitory effect on
      tumor formation. These results suggested that SNL-A may be a potential, natural
      apoptosis-inducing agent for cervical cancer.

PMID- 18717491
TI  - Enniatins produced by Fusarium dimerum, an endophytic fungal strain.
AB  - Cyclohexadepsipetides enniatin B, B1 and G were isolated from the cultivation
      broth of Fusarium dimerum Penzig, an endophyte of Magnolia x soulangeana. Their
      production was about 350 mg l(-1) after 96 h of submerged cultivation in
      Sabouraud maltose medium. Isolated enniatins inhibited growth of selected
      microorganisms and activity of 12-lipoxygenase with IC50 = 0.73 mg l(-1).

PMID- 18717492
TI  - Minor compounds from the stem bark of Chinese mangrove associate Catunaregam
      spinosa.
AB  - A new dihydroisocoumarin 3-(2-hydroxypropyl)-8-hydroxyl-3,4-dihydroisocoumarin
      (1) and a new iridoid 3-deoxyartselaenin C (5), together with six known compounds
      scopoletin (2), scoparone (3), morindolide (4), pinoresinol (6), medioresinol
      (7), and secoisolariciresinol (8) were isolated from the stem bark of Chinese
      mangrove associate Catunaregam spinosa Tirveng. The structures of 1 and 5 were
      determined by extensive spectroscopic analysis, including 1D and 2D NMR data. All
      compounds except 2 were obtained from C. spinosa for the first time. And it was
      also the first time lignans were obtained from Catunaregam sp.

PMID- 18717493
TI  - Influence of lag-time between light exposure and color evaluation of riboflavin
      in the solid state.
AB  - The lag-time between sample light exposure and evaluation of the samples strongly
      influences the observed change in surface color of riboflavin bulk substance and
      tablets. The decrease in total color change (deltaE*ab) as a function of time
      after exposure is ascribed to a change in the surface moisture content of the
      samples during storage. Our results emphasize the need for a standardization of
      the lag-time between light exposure and sample evaluation in the photostability
      testing protocol of drug substances and products.

PMID- 18717494
TI  - Influence of pre-systemic modifications on the drug performance.
AB  - Influences of technological and other pre-systemic modifications on the drug
      performance play a pivotal role in drug development and optimization. The paper
      evaluates these influences within a framework of the sensitivity theory.
      Deviations of the drug performance that were caused by modified pre-systemic
      parameters are predicted and compared with those obtained in vivo. A close
      correspondence between them demonstrates feasibility of the approach presented
      and its usability as an alternative or suplementary means of the in vitro-in vivo
      correlation analysis.

PMID- 18717495
TI  - Solubility prediction of solutes in aqueous mixtures of ethylene glycols.
AB  - The applicability of a trained version of the Jouyban-Acree model, for predicting
      the solubility of solutes in aqueous mixtures of ethylene glycol and its
      polymerized forms was shown. The solubilities of 8 drugs in binary mixtures were
      determined and the mean percentage deviation (MPD) was calculated as a prediction
      accuracy criterion and the overall MPD (+/- SD) was 23.2 (+/- 13.1)%.

PMID- 18717496
TI  - Lab pro's new perspective.

PMID- 18717497
TI  - Kudos to Haitian volunteers.

PMID- 18717498
TI  - Cystic fibrosis: newborn screening in America.
AB  - Cystic fibrosis is the most common lethal genetic disease in Caucasians,
      manifesting as progressive lung dysfunction, pancreatic insufficiency, and
      intestinal disease. CF was traditionally diagnosed clinically, either because of
      a family history or occurrence of meconium ileus, or as a result of intestinal
      malabsorption and chronic pulmonary disease. In 1979, it was discovered that
      immunoreactive trypsinogen was increased in neonatal dried-blood specimens on
      Guthrie cards, making it possible to screen neonates. During the past decades,
      survival rates of patients with CF have improved significantly (see Figure 5). To
      continue this progress, universal newborn screening has been implemented in many
      states as an addition to the arsenal of therapies and strategies to improve
      survival. National newborn-screening programs to identify CF patients after birth
      have been adopted for a number of years in Europe, Australia, and Canada. As
      expected, many benefits have been seen due to the early identification of CF
      patients, including improved survival, better lung function and growth with less
      intensive therapy, and reduced cost of therapy. To date, 37 states in the United
      States have adopted similar programs, in the hopes of improving CF outcomes. This
      welcome trend should help improve the lives of CF patients living in America.

PMID- 18717499
TI  - Where the heroes are: testing in a war zone.

PMID- 18717500
TI  - States fail to follow California's lead in certifying phlebotomists.

PMID- 18717501
TI  - Microbiology lab automation arrives.

PMID- 18717502
TI  - Kershaw helps shape Sysmex' healthcare advancement.

PMID- 18717503
TI  - Polls reveal MRSA controls.

PMID- 18717504
TI  - Addressing management issues. Training a new supervisor.

PMID- 18717505
TI  - Liability. Kids' "go-to-work day" problems.

PMID- 18717506
TI  - Compensation trends for lab executives.

PMID- 18717507
TI  - Opioid-induced hyperalgesia: pathophysiology and clinical implications.
AB  - BACKGROUND: Opioid-induced hyperalgesia (OIH) refers to a phenomenon whereby
      opioid administration results in a lowering of pain threshold, clinically
      manifest as apparent opioid tolerance, worsening pain despite accelerating opioid
      doses, and abnormal pain symptoms such as allodynia. AIM: The current review,
      while providing a clinically oriented updated overview on the pathophysiology of
      OIH, focuses predominantly on evidence-based clinical and management aspects of
      this important and often baffling phenomenon. METHOD: Online and manual search
      using key words such as opioid-induced hyperalgesia, opioid-induced abnormal pain
      sensitivity, opioid hyperalgesia, opioid-induced paradoxical pain, or opioid
      induced abnormal pain, followed by full-text access and further crossreferencing.
      RESULTS: The underlying pathophysiology of this phenomenon, although still
      unclear, appears to be related to an opioid-induced imbalance between the
      internal antinociceptive and pronociceptive systems. Clinical differentiation of
      an apparent opioid tolerance state includes OIH. Once diagnosed or provisionally
      considered, treatment strategies could include opioid dose reduction, opioid
      rotation, use of agents with NMDA receptor antagonism, and a properly timed
      coxib. CONCLUSION: Despite initial skepticism and reservations, the phenomenon of
      OIH in humans is now accepted a clinical reality and a challenge faced by
      anesthesiologists, intensivists, pain specialists, and other workers in a diverse
      range of settings from perioperative care to palliative care medicine.

PMID- 18717508
TI  - Oxymorphone and oxymorphone extended release: a pharmacotherapeutic review.
AB  - The treatment of chronic pain remains an enormous challenge in the United States.
      Opioid analgesics are an important component of pharmacotherapy for chronic pain
      and have proven efficacy in the management of cancer and noncancer chronic pain.
      The newest addition to oral opioid pharmacotherapy is oral oxymorphone, a
      semisynthetic opioid agonist that is now available in oral immediate-release (IR)
      and extended-release (ER) formulations. This review discusses the pharmacology,
      pharmacokinetics, pharmacodynamics, pharmacotherapeutics, and clinical use of
      oral oxymorphone IR and ER formulations for the management of moderate to severe
      pain for different types of patients in a variety of settings. Two published
      studies evaluated the efficacy and safety of oxymorphone IR in patients with
      moderate to severe postoperative pain and demonstrated that it provides rapid and
      effective analgesia and is generally well tolerated. Six published randomized
      controlled trials and three published open-label studies evaluated the efficacy
      and safety of oxymorphone ER for chronic cancer or noncancer pain. These trials
      found analgesic efficacy and tolerability comparable to that provided by morphine
      controlled release (CR) or oxycodone CR; treatment effects with oxymorphone ER
      were durable for treatment periods of 12 weeks at the same dose or up to 1 year
      with little dose escalation. Titrated doses of oxymorphone ER were effective and
      generally well tolerated in both opioid-experienced and opioid-naive patients.
      Aspects of oxymorphone metabolism and limited protein binding may simplify
      treatment in certain populations.

PMID- 18717509
TI  - Epidemiology of opioid pharmacy claims in the United States.
AB  - OBJECTIVE: To describe opioid pharmacy claims patterns in the United States among
      an insured population. DESIGN: Information was obtained from the US insurance
      claims database, IMS Lifelink, between 1997 and 2002. Descriptive statistics of
      opioid claims patterns were described with stratification by gender, age, and
      year of use. RESULTS: The prevalence of insured people with opioid claims
      increased from 17.1 percent in 1997 to 18.4 percent in 2002. Among people with an
      opioid claim, 24 percent had > or =30 days and 10 percent had > or =90 days of
      days supplied based on the insurance claims. Prevalence varied by type of opioid;
      56 percent of people with a claim received propoxyphene, 43 percent received
      codeine, 23 percent received oxycodone, and 17 percent received hydrocodone.
      Sustained-release opioids were found among 6 percent of those with a claim. With
      respect to the dose of opioids in the pharmacy claims (expressed as morphine
      equivalent total daily dose), 71 percent had claims for <50 mg, 55 percent had
      claims for 50-99 mg, and 24 percent had claims for > or =100 mg. Women,
      individuals with cancer, and older patients had significantly more pharmacy
      claims as well as claims for higher doses of opioids (p < 0.05). Internal
      medicine and family practice specialists were responsible for 22.4 percent and
      20.9 percent of all opioid claims. CONCLUSIONS: Opioid pharmacy claims increased
      slightly over time. Older patients, women and patients with a cancer diagnosis
      had significantly more opioid claims and claims for higher doses than the younger
      patients, men, and those without cancer.

PMID- 18717510
TI  - Role of patient-based health status outcome measurements in opioid management for
      low back pain.
AB  - OBJECTIVE: The aim of the study was to identify patient factors that correlate
      with a strong response to opioid pain medications in low back pain patients.
      DESIGN: Prospective analysis. SETTING: Tertiary Institutional Spine Care Center.
      PATIENTS, PARTICIPANTS: All patients visiting a tertiary referral spine center
      with primary diagnosis of low back pain (n = 486) and minimum duration of 6
      months. INTERVENTIONS: Opioid medication. MAIN OUTCOME MEASURES: Analysis factors
      included visual analog pain scale (VAS), symptom relief scores, and results on 36
      item Short Form Health Survey (SF-36). A longitudinal descriptive analysis and a
      multivariable logistic regression were performed on the results of the VAS and SF
      36 scores. RESULTS: The average age of opioid and nonopioid treated patients was
      62 years versus 64 years, (p = 0.13) and gender distributions at 53 percent
      versus 50 percent female (p = 0.43). SF-36 scores were statistically significant
      and associated with the opioid categorization. For every unit increase in symptom
      relief score, the likelihood of opioid use is doubled (OR = 2.1, 95 percent CI =
      1.5-2.8, p < 0.001); and increased by 25 percent with each 10-point decrease in
      the social functioning quality of life score (OR = 0.98, 95 percent CI = 0.96
      0.99, p = 0.006). CONCLUSIONS: Social quality of life and symptom relief
      measurements comprise the optimal set of independent factors that correlate most
      strongly with a response to opioid use in low back pain patients.

PMID- 18717511
TI  - Epidural haloperidol enhances epidural morphine analgesia: three case reports.
AB  - Epidural opioids provide significant postoperative analgesia; however, their use
      is often limited by side effects such as nausea and pruritus, or they require the
      addition of epidural local anesthetics with possible side effects of motor block
      and hypotension. Adjuncts to epidural opioid analgesia would benefit pain
      management. There is evidence that epidural butyrophenones may enhance opioid
      analgesics and reduce side effects. The authors present the first reported use of
      epidural haloperidol to enhance epidural morphine analgesia in three individuals.
      Pharmacodynamic interactions of haloperidol, which may explain its analgesic
      efficacy, are summarized.

PMID- 18717512
TI  - Tapering chronic opioid therapy in neuropathic facial pain: an interdisciplinary
      approach.
AB  - This case report presents a patient with chronic orofacial pain who was
      considered to be an appropriate candidate for chronic opioid therapy, a treatment
      uncommonly considered at most facial pain centers. Her opioid treatment proved
      ineffectual, and conservative approaches were addressed. She was successfully
      tapered off the use of a long-acting opioid within a relatively short time, using
      an interdisciplinary approach involving an aggressive biobehavioral approach.

PMID- 18717513
TI  - Ketamine for acute and subacute pain in opioid-tolerant patients.
AB  - Prolonged acute pain, especially that of oncologic neurological origin, is at
      times difficult to control; it is seldom entirely alleviated by opioids. We
      report eight patients with severe pain, three of whom suffered from new onset
      oncologic metastatic bone pain, others had previous pain syndromes and presented
      with exacerbation of pain. Pain was associated with hyperalgesia and allodynia
      phenomena in two patients and with phantom pain in a third one. Tolerance to
      opioids had developed, and high IV doses of morphine, meperidine or fentanyl, and
      patient-controlled intravenous and epidural analgesia were insufficient. Several
      patients became dependent on opioids and could not be weaned from assisted
      ventilation. Pain was controlled with decreasing adjunct doses of ketamine.
      Within 5-10 days of ketamine and opioid protocols, pain was controlled and after
      an additional 5-7 days, ketamine could be stopped and pain controlled on oral
      regimens compatible with outpatient care. Ketamine is an efficient adjuvant
      analgesic for intractable severe pain, caused by metastasis, trauma, chronic
      ischemia, or central neuropathic pain. It is effective even when mega doses of
      IV, epidural, or oral opioids prove ineffective and when signs of tolerance have
      developed.

PMID- 18717514
TI  - A review of conflict of interest, competing interest, and bias for toxicologists.
AB  - One of the issues often associated with scientific misconduct is conflict of
      interest. Although there is a lack of uniformity in the definition of conflict of
      interest, many express concerns that competing interests may bias research
      methods and the interpretation of data and conclusions. In extreme cases,
      conflict of interest activity could contribute to scientific misconduct, hinder
      the training of scientists, delay the dissemination of research results, lead to
      the harming of human health and the environment, and misdirect society's
      decisions that rely on science. This article is not a commentary or editorial but
      an attempt to supply an overview of what has been said, researched, and
      accomplished in the area of conflict of interest for toxicologists. Discussion of
      the financial, professional, and philosophical concerns associated with conflict
      of interest will be followed by brief discussion of general management approaches
      and the roles of scientists and organizations from all sectors (i.e., academia,
      industry, non-profit organizations, and government).

PMID- 18717515
TI  - Protective effect of melatonin against formaldehyde-induced kidney damage in
      rats.
AB  - This study was undertaken to investigate the protective effects of melatonin
      against formaldehyde-induced renal damage in rats. For this purpose, 21 male
      Wistar rats were divided into three groups. The animals in Group I were used as a
      control, whereas the rats in group II were injected every other day with
      formaldehyde. The rats in group III received melatonin daily while exposed to
      formaldehyde. At the end of the 14-day experimental period, all rats were killed
      by decapitation, and the kidneys were removed. Some of the renal tissue specimens
      were used for determination of superoxide dismutase, glutatione peroxidase enzyme
      activities, and malondialdehyde levels. The remaining kidney tissue specimens
      were used for light microscopic evaluation. The renal tissue activities of
      superoxide dismutase and glutatione peroxidase were significantly decreased, and
      malondialdehyde levels were significantly increased in rats treated with
      formaldehyde compared with those of the control animals. In the light microscopic
      evaluation of this group, degenerative glomerules, vacuolization and dilatation
      of distal tubules, and vascular congestion were detected. However, an increase
      was observed in activities of superoxide dismutase and glutatione peroxidase
      enzymes, and a decrease of malondialdehyde levels in animals treated with
      formaldehyde plus melatonin was observed. Furthermore, the histopathological
      changes caused by formaldehyde were disappeared except for minimal tubular
      dilatation in this group. In conclusion, the biochemical and histological
      findings of our study suggest that melatonin administration prevents formaldehyde
      induced oxidative renal damage in rats.

PMID- 18717516
TI  - Levels of retinyl palmitate and retinol in the skin of SKH-1 mice topically
      treated with retinyl palmitate and concomitant exposure to simulated solar light
      for thirteen weeks.
AB  - Retinyl esters account for more than 70% of the endogenous vitamin A found in
      human skin, and retinyl palmitate is one of the retinyl esters in this pool.
      Human skin is also exposed to retinyl palmitate exogenously through the topical
      application of cosmetic and skin care products that contain retinyl palmitate. To
      date, there is limited information on the penetration and distribution of retinyl
      palmitate and vitamin A within in the skin. In this study, the accumulation of
      retinyl palmitate and generation of retinol in the skin of male and female SKH-1
      mice that received repeated topical applications of creams containing 0.0%, 0.1%,
      0.5%, 1.0%, 5.0%, 10%, or 13% of retinyl palmitate 5 days a week for a period of
      13 weeks were studied. Because products containing retinyl palmitate are
      frequently applied to sun-exposed skin, and because it is well established that
      exposure to sunlight and UV light can alter cutaneous levels of retinoids, mice
      in this study were additionally exposed 5 days a week to simulated solar light.
      The results showed that retinyl palmitate diffused into the skin and was
      partially hydrolyzed to retinol. The levels of retinyl palmitate in the skin of
      mice that were administered retinyl palmitate cream were higher than control
      values, and levels of both retinyl palmitate and retinol increased with the
      application of higher concentrations of retinyl palmitate in the cream. Our
      results indicate that topically applied retinyl palmitate may alter the normal
      physiological levels of retinyl palmitate and retinol in the skin of SKH-1 mice
      and may have a significant impact on vitamin A homeostasis in the skin.

PMID- 18717517
TI  - Preventive role of folic acid on the developmental toxicity of phenol in
      Drosophila melanogaster.
AB  - Phenol (PN), obtained from coal tar, is used commonly in medical treatments,
      industrial areas, petroleum refineries, production of glue, fiber, and nylon. PN
      is used in the production of benzene and it is emitted in the atmosphere by motor
      vehicles. Folic acid (FA) is an essential nutrient among the B complex group of
      vitamins. The main aim of this study was to investigate the effects of PN and PN
      + FA on various developmental stages of Drosophila melanogaster. Different
      concentrations of PN and PN + FA were administered during the developmental
      periods of the fly (egg, larva and pupa). When F1 progeny of control and
      experimental groups were compared, PN was found to extend the process of
      metamorphosis and decrease the total offspring numbers. However, these negative
      effects were inhibited by FA treatment at different concentrations (0.25-2.50
      mg/kg). These results suggest that FA could effectively inhibit PN-induced
      abnormalities in developmental stages of Drosophila melanogaster.

PMID- 18717518
TI  - The periodontal status of indirectly lead-exposed apprentices working in
      autorepair workshops.
AB  - The aim of this study was to evaluate the periodontal health status of lead
      exposed apprentices and to search the correlation between clinical periodontal
      parameters and either blood lead or oxidative stress/damage indices in
      erythrocytes. Sixty male subjects were recruited for this study (30 apprentices
      and 30 controls). The periodontal health status was determined with gingival
      index, plaque index, gingival bleeding time index, probing depth, and clinical
      attachment level records. Additionally, blood lead level and indices of oxidative
      stress (glutathione peroxidase, superoxide dismutase), catalase activities and
      damage (malondialdehyde concentration) in erythrocytes were determined. The
      results showed that lead level was significantly higher in apprentices than in
      controls (P < 0.05). None of the clinical periodontal parameters and oxidative
      stress/damage indices were significantly different between the groups (P > 0.05).
      Significant correlation between plaque index and catalase, probing depth and
      superoxide dismutase, clinical attachment level and superoxide dismutase, and
      clinical attachment level and malondialdehyde in apprentices group (P < 0.05),
      and gingival bleeding time index and glutathione peroxidase in control group were
      found (P < 0.05). In multiple regression analysis, there were statistically
      significant associations between gingival index and working status, family income
      and either probing depth or clinical attachment level (P < 0.05). The results of
      this study showed significant association between the clinical periodontal
      parameters and oxidative stress/damage indices in apprentices indirectly exposed
      to low levels of lead.

PMID- 18717519
TI  - Redefining idiopathic interstitial lung disease into occupational lung diseases
      by analysis of chemical composition of inhaled dust particles in induced sputum
      and/or lung biopsy specimens.
AB  - There has been increased public awareness of the potential danger from exposure
      to hazardous dust in various occupations. This study aims to validate the
      qualitative analysis of scanning electron microscopy (SEM) of lung samples by 1)
      correlation of induced sputum (IS) findings to clinical findings, 2) comparing
      hazardous particles in IS to those in biopsied lung specimens, and 3) assessing
      whether the particles present in the lungs of transplanted patients correlate
      with occupational history of dust exposure. Forty patients with occupational
      history were included; of whom 35 filled in questionnaires. Twenty-four of them
      had SEM analysis of their IS, and 11 of these 24 also had SEM analysis of their
      lung tissue. Another 11 lung biopsies from patients with occupational history
      were scanned by SEM and compared with 10 lung biopsies from patients with no
      occupational history. SEM analysis of IS was as efficient for detecting hazardous
      particles as was SEM analysis of lung tissue; silica was detected better in
      sputum. Exposure to silica was the main chemical element associated with a high
      likelihood to show abnormalities in IS (Odds ratio 19.41 CI = 0.270-1398.33). The
      average number of detected hazardous chemical elements in patients with an
      occupational history of exposure was 4 +/- 1.61 in IS and 3.55 +/- 2.02 in lung
      tissue (P = 0.57); it was 1.5 +/- 0.85 from transplanted occupationally exposed
      patients compared with 0.36 +/- 0.67 in transplanted non-exposed patients (P =
      0.003). SEM analysis of particles in IS and lung tissue can elucidate the
      causative agent(s) of otherwise idiopathic interstitial lung disease among
      occupationally exposed workers.

PMID- 18717520
TI  - JP-8 jet fuel exposure potentiates tumor development in two experimental model
      systems.
AB  - The US Air Force has implemented the widespread use of JP-8 jet fuel in its
      operations, although a thorough understanding of its potential effects upon
      exposed personnel is unclear. Previous work has reported that JP-8 exposure is
      immunosuppressive. Exposure of mice to JP-8 for 1 h/day resulted in immediate
      secretion of two immunosuppressive agents; namely, interleukin-10 (IL-10) and
      prostaglandin E2 (PGE2). Thus, it was of interest to determine if jet fuel
      exposure might promote tumor growth and metastasis. The syngeneic B16 tumor model
      was used for these studies. Animals were injected intravenously with tumor cells,
      and lung colonies were enumerated. Animals were also examined for metastatic
      spread of the tumor. Mice were either exposed to 1000 mg/m3 JP-8 (1 h/ day) for 7
      days before tumor injection or were exposed to JP-8 at the time of tumor
      injection. All animals were killed 17 days after tumor injection. In the present
      study, JP8 exposure potentiated the growth and metastases of B16 tumors in an
      animal model. Exposure of mice to JP-8 for 1 h/day before tumor induction
      resulted in an approximately 8.7-fold increase in tumors, whereas those mice
      exposed to JP8 at the time of tumor induction had a 5.6-fold increase in tumor
      numbers. Thus, low concentration JP-8 jet fuel exposures have significant immune
      suppressive effects on the immune system that can result in increased tumor
      formation and metastases. We have now extended the observations to an
      experimental subcutaneous tumor model. JP8 exposure at the time of tumor
      induction in this model did not affect the growth of the tumor. However, JP8
      exposed, tumor-bearing animals died at an accelerated rate as compared with air
      exposed, tumor-bearing mice.

PMID- 18717521
TI  - UVA photoirradiation of anhydroretinol--formation of singlet oxygen and
      superoxide.
AB  - Anhydroretinol is a metabolite of vitamin A (retinol) and a major
      photodecomposition product of retinyl palmitate and retinyl acetate.
      Anhydroretinol is biologically active, inducing cell death in lymphoblastoid
      cells, prevention of N-methyl-N-nitrosourea-induced mammary cancer, and
      inhibition of cell growth in lymphocytes. We have previously determined that
      photoirradiation of anhydroretinol in the presence of a lipid, methyl linoleate,
      with UVA light-induced lipid peroxidation. In the present study, electron spin
      resonance (ESR) spin-trap techniques were employed to explore the mechanism of
      lipid peroxidation initiation. Irradiation of anhydroretinol by UVA in the
      presence of 2,2,6,6-tetramethylpiperidine (TEMP), a specific probe for singlet
      oxygen, resulted in the formation of TEMPO, indicating that singlet oxygen was
      generated. During photoirradiation in the presence of 5,5-dimethyl N-oxide
      pyrroline (DMPO), a specific probe for superoxide, ESR signals for DMPO-OOH were
      formed, and these signals were quenched by superoxide dismutase. The involvement
      of singlet oxygen on the induction of lipid peroxidation was also evidenced by
      the observation that lipid peroxidation was inhibited by sodium azide and
      enhanced by deuterium oxide. Our overall results provide evidence that
      photoirradiation of anhydroretinol with UVA light generates reactive oxygen
      species, e.g. singlet oxygen and superoxide, which mediate the induction of lipid
      peroxidation.

PMID- 18717522
TI  - Upper limb disorders due to biomechanical overload in the upholstered furniture
      industry.

PMID- 18717523
TI  - [Manufacture of upholstered furniture and work-related upper limb musculoskeletal
      disorders: an industrial sector prevention project].
AB  - BACKGROUND: In cooperation with the IRCCS Fondazione Maugeri and the IRCCS
      Fondazione Ospedale Maggiore Policlinico - EPM-CEMOC, of Milan, the Local Health
      Unit in Bari, Italy carried out a research project, sponsored partly by the
      Italian Ministry of Health, on upper limb work-related musculoskeletal disorders
      (UL-WMSDs) in a specific manufacturing sector, the upholstered furniture
      industry. This "sofa district" is widely represented with approximately 14,000
      workers and 500 factories over a wide geographic area of southern Italy. Advanced
      technology in the manufacturing process is combined with workers performing
      intensive arm-hand tasks. OBJECTIVES: The aim of the study included: a)
      assessment of exposure to repetitive strain and movements of the upper limb in a
      representative sample of the factories using the OCRA method, b) analysis of the
      annual prevalence and incidence rates, c) definition of possible improvement via
      ergonomic solutions in the various factories. METHODS: Via a network of
      occupational physicians a total of more than 6000 subjects were examined over a 5
      year period. Case-definition was assessed through standardized procedures.
      RESULTS: A detailed description of the manufacturing process of the upholstered
      furniture industry and of the characteristics of the working population is
      provided Exposed groups at risk were:filling preparation workers, leather-cutting
      operators, sewing and upholstery-assembly workers. CONCLUSIONS: Data collected in
      private companies of different size in this extensive industrial "sofa area"
      emphasize the importance of prevention through adequate ergonomic solutions and
      the need to improve training programmes covering the whole area.

PMID- 18717524
TI  - [Risk assessment of work-related upper limb musculoskeletal disorders in thirty
      factories in the upholstered furniture industry].
AB  - BACKGROUND: One of the most common procedures for risk assessment of upper limb
      work-related musculoskeletal disorders (UL-WMSDs) in Italy is the OCRA synthetic
      index, which is recommended as the preferred method in the ISO standard 11228-3.
      OBJECTIVE: The aim of the survey was to assess the risk of UL-WMSDs due to
      repetitive strain and movements in thirty factories of the sofa industry located
      in a large geographic area of southern Italy. METHODS: The most characteristic
      working tasks of the manufacturing process were studied: filling preparation
      workers, leather-cutting operators, sewing and upholstery-assembly workers. The
      single tasks were carried out almost exclusively manually, with features of a
      handicraft approach. Data were collected through questionnaires and video tape
      recordings in each factory. The mean value of the OCRA index of every group of
      factories was calculated by weighting the values of the index of each single task
      group with the number of the workers. RESULTS: Figures obtained in the different
      factories showed values of the OCRA index ranging between 4 and 15. A 2,9 OCRA
      value was attributed to a low exposure group. CONCLUSIONS: Even though the work
      tasks analyzed were characterized by long duration of the manufacturing cycle
      (between 5 and 60 min), a particular but rigorous application of the OCRA
      procedures made it possible for a detailed risk assessment to be made for each of
      the working groups analysed.

PMID- 18717525
TI  - [Prevalence of upper limb work-related musculoskeletal disorders (UL-WMSDs) in
      workers of the upholstered furniture industry].
AB  - BACKGROUND: The upholstered furniture industry, the so-called "triangle of the
      sofa industry", is a geographic area of national and strategic economic
      importance in southern Italy. The single tasks are carried out mostly manually,
      with the characteristics of a handicraft approach. OBJECTIVES: The aim of the
      survey was to assess the prevalence of upper limb work-related musculoskeletal
      disorders (UL-WMSDs) in 30 factories of the sofa industry located in a large
      geographic area of the Puglia and Basilicata Regions. METHODS: In the period 1
      January-31 December 2003 a network of occupational physicians investigated a
      population of 5.477 subjects (exposed n=3481, controls n=1996, M=3865, F=1612) in
      30 different factories of the area. More than 60 percent of the total workforce
      studied was employed in large-sized companies (>500 employees). The following
      work tasks were considered: filling preparation workers, leather-cutting
      operators, sewing and upholstery-assembly workers. Case-definition was assessed
      through standardized procedures: symptoms by questionnaire plus physical and
      laboratory/imaging findings. RESULTS: Cumulative prevalence rates of UL-WMSDs as
      at 31 December 2003 reached values of up to 30% in high risk groups. Prevalence
      rates showed good correlation with the concise OCRA index used for assessment of
      exposure to repetitive strain and movements of the upper limb. The most
      frequently occurring disorders were tendon-related cysts and wrist tendonitis.
      Shoulder disorders were more frequent in male and female leather-cutting
      operators. CONCLUSIONS: This survey showed a significantly high prevalence of UL
      WMSDs in sofa industry workers. It did not seem to be confirmed in this study
      that there was a greater female susceptibility to UL-WMSDs with the exception of
      carpal tunnel syndrome: gender difference seems to be less relevant at increasing
      levels of occupational exposure to repetitive movements and exertion of the upper
      limbs.

PMID- 18717526
TI  - [Upper limb work-related musculoskeletal disorders (UL-WMSDs): a retrospective
      cohort study in three large factories of the upholstered furniture industry].
AB  - BACKGROUND: The epidemiological evidence of work-related musculoskeletal
      disorders (UL-WMSDs) due to repetitive strain and movements in the various
      industries has been collected in the literature mainly through cross-sectional
      surveys. In particular there are no contributions so far regarding the
      upholstered furniture industry with a longitudinal design. OBJECTIVES: The aim of
      the study was to evaluate the incidence rate of WMSDs such as hand-wrist and
      shoulder tendonitis, carpal tunnel syndrome, and epicondylitis in exposed workers
      of three large companies of the upholstered furniture industry in a large
      geographic area of southern Italy. METHODS: The OCRA method, recommended by
      international standard ISO 11228-3 and EN 1005-5, was used for risk assessment.
      The following work tasks were considered:.filling preparation workers, leather
      cutting operators, sewing and upholstery-assembly workers. A total population of
      5,278 subjects (exposed n=2927, controls n=2351) was investigated. The
      person/year at risk parameters were calculated from 1 January 2000, or from the
      date of engagement if later, until the first diagnosis of WMSD or, in absence of
      disorders, until the end of the study, i.e. 31 December 2004. Disorders occurring
      after the first were not considered. A multiple regression analysis was used to
      evaluate relationships between rates. RESULTS AND CONCLUSIONS: Incidence rates
      correlated with risk classes of the OCRA index. An incidence rate of WMSDs higher
      than 1.2 cases per 100 person/year may be considered as a threshold value to
      suspect an occupational exposure to repetitive strain and movements warranting
      further investigation. The analysis of single factors did not show a greater
      predisposition of the female gender, with the single exception of the carpal
      tunnel syndrome (RR 2.92; 95% CI 1.57-5.43). Shoulder disorders affected mainly
      male leather-cutting operators (RR 4.97; 95% CI 2.03-12.16) and among all the
      factors influencing risk (frequency, force, posture, additional risk factors,
      pauses) posture seems to play a significant role.

PMID- 18717527
TI  - [Upper limb work-related musculoskeletal disorders (UL-WMSDs) in a large factory
      of the upholstered furniture industry: risk management].
AB  - BACKGROUND: The industrial production of upholstered furniture exposes workers to
      significant risk of occupational disorders due to ergonomics-related problems,
      such as repetitive strain and movements of the upper limb, manual load lifting,
      prolonged static postures. OBJECTIVE: This paper describes the main measures
      taken by the biggest company in the "sofa sector" in southern Italy in order to
      solve such problems in the years 1996-2004. METHODS: the classic instruments of
      ergonomics were used such as risk assessment, medical surveillance, training and
      information programmes, technological reorganization of the manufacturing process
      and of single working tasks. RESULTS: The accident rate (number of accidents per
      million working hours) which showed an increasing trend in the previous years,
      rose from a value of 31 in 1996 to 51 in the years 1999-2000 (with a percentage
      of accidents related to load lifting in the range 25-35%). At the same time the
      incidence rate of work-related upper limb musculoskeletal disorders (UL-WMSDs) in
      the population of workers (which had increased in the meantime from 2500 to 3500
      employees) reached nearly 5% in 2001, with peaks of 8-9% in the work tasks with
      higher exposure. Accident rates progressively fell in the following three years
      until a value of 20 was reached in 2004 and 2005, while the mean incidence rate
      of WMSDs reached a value of nearly 1%. The data need to be compared with the
      trends in the other companies of the sector in the same period, with an average
      incidence rate of WMSDs around 2% and a generally increasing trend. CONCLUSIONS:
      Ergonomic interventions not only concur in the management and control of negative
      events for workers health but also in achieving advantages in terms of lower
      costs and greater productivity.

PMID- 18717528
TI  - [From mandatory to participatory prevention: a model applied to the upholstered
      furniture industry].
AB  - BACKGROUND: The Italian 2006-2008 National Health Plan emphasizes synergy and
      cooperation between the agencies formally involved in the prevention of
      occupational risks, in agreement with social partners. The so-called 'triangle of
      the sofa industry' is an interregional geographic area south-west of Bari, Italy.
      In 2003 this area produced 16% of the world-wide upholstered furniture output,
      with more than 500 plants of varying size. OBJECTIVE: The aim was to set up a
      network of communication and cooperation between the competent Agencies and
      Regions in order to address the rising trend of upper limb work-related
      musculoskeletal disorders. METHODS: The first step of the National Health Service
      Unit in Bari was to assess risk via a Ministerial research project and implement
      various information campaigns involving institutions, occupational physicians,
      private companies and public opinion. In a subsequent phase a synergy between the
      local Departmenst ofPrevention of the different Regions, the Italian Institute
      for Insurance Occupational Accidents and Disease (INAIL), the trade unions and
      the upholstered furniture industry Association was established. RESULTS AND
      CONCLUSIONS: New joint experimental projects (cutting tools, ergonomic table for
      assemblers, instruments for isokinetic evaluation) were launched together with
      training programmes for management, safety technicians and workers. This kind of
      'participatory prevention' is more appropriate for the goal of a collaborative
      effort in order to assist the companies, which is a modern interpretation of the
      mission of public health prevention operators.

PMID- 18717529
TI  - [Always apropos of certification obligations].

PMID- 18717530
TI  - Analysis of lipid peroxidation kinetics. 1. Role of recombination of alkyl and
      peroxyl radicals.
AB  - The kinetics of the lipid peroxidation reaction is only partly understood.
      Although the set of reactions constituting the overall reaction are believed to
      be known, it has not been possible to predict how the reaction will respond to a
      change of one or more of the parameters, e.g., initial concentrations of
      reactants or different ways of initiating the reaction, nor has it been possible
      to predict the time dependence of the products. The reason for these problems is
      the complicated structure of the kinetic scheme, which includes a chain reaction.
      In this work we perform an in-depth analysis of the importance of the individual
      reaction steps, and we introduce a new quasi-stationary concentration method
      based on the assumption that one or more concentrations vary much slower than the
      others. We show that it is justified to use a quasi-stationary concentration
      approximation for the alkyl radical L*, but not for the peroxyl radicals LO2 * as
      assumed in previous works. The method allows us to derive manageable analytical
      expressions. On the basis of literature values of the rate constants, we are able
      to introduce specific simplifications that allow us to obtain simple analytical
      expressions for the time dependence of all concentrations involved in the
      process.

PMID- 18717531
TI  - Localized therapeutic release via an amine-functionalized poly-p-xylene microfilm
      device.
AB  - Developing biocompatible polymeric platforms for drug delivery with enhanced
      localized activity represents a key facet of advanced interventional therapy. In
      this work, the drug-eluting potential of an amine-functionalized poly- p-xylene
      commonly known as Parylene A (4-amino(2,2)paracyclophane) was conducted with the
      microfilm device consisting of a primary base layer, drug film, and a secondary
      eluting layer presenting exposed amine groups which enhance the range of
      modifications that can be incorporated into the film. The murine macrophage cell
      line RAW 264.7 served as a cellular response to dexamethasone, a synthetic anti
      inflammatory glucocorticoid and doxorubicin, an anticancer therapeutic. Decreased
      expression of NFkappa-B-mediated cytokines Interleukin-6 (IL-6) and Tumor
      Necrosis Factor-alpha (TNFalpha), resultant DNA fragmentation, and spectroscopic
      analysis revealed the efficient and localized drug-eluting properties of the
      Parylene A polymeric bilayer.

PMID- 18717532
TI  - Environmental and excitonic effects on the first hyperpolarizability of polar
      molecules and related dimers.
AB  - We investigate the second-order nonlinear optical properties of a push-pull
      chromophore in different external and supramolecular environments, through a
      combined experimental and theoretical approach. In particular, we compare the
      first hyperpolarizability (beta) of a model dipolar and polarizable chromophore
      with that of a charged analogue and of a molecular dimer based on the chromophore
      itself. We find that the beta value of the model chromophore in solutions of low
      polarity solvents is strongly affected by association effects, already at
      concentrations of 10 (-3) M. The presence of a positive charge in close proximity
      to the chromophore is found to lead to a 100% increase of the beta response of
      the model push-pull chromophore. This effect is of major importance for
      biological applications, in particular when chromophores are used as markers in
      charged anisotropic environments. Finally, excitonic effects, beyond the Frenkel
      exciton approximation, are discussed for the dimer and found to be more important
      the higher the order of nonlinearity is.

PMID- 18717533
TI  - Dewetting pathways and morphology of unstable thin liquid bilayers.
AB  - Three-dimensional long-wave nonlinear analysis of the instabilities engendered by
      van der Waals forces in a thin (<100 nm) viscous bilayer resting on a rigid
      substrate is presented. The bilayers are classified based on the macroscopic
      dewetting behavior of the films, and the three-dimensional morphological
      evolutions of the films are studied in each case. The dewetting of the bilayers
      is initiated by one of the two basic modes at the interfaces: in-phase "bending"
      and out-of-phase "squeezing". We show that the thicknesses, surface energies, and
      viscosities of the films have significant influence on the mode selection,
      pathway, of dewetting, and the final morphology of dewetting. Different
      equilibrium morphologies are obtained by tuning the nature and the strength of
      the intermolecular forces present at the films, which include: (i) an array of
      channels and ridges in the lower layer with the upper liquid embedded inside the
      channels, (ii) islands in the lower layer with the upper layer embedded in the
      interstitial spaces, and (iii) the lower layer droplets encapsulated by the upper
      layer.

PMID- 18717534
TI  - Environment-induced surface dynamics of a biomimetic ionomer studied using in
      situ second harmonic generation.
AB  - The environmental-induced surface dynamics of the biomimetic phosphoryl choline
      (PC)-functionalized poly(trimethylene carbonate) ionomer has been studied and
      compared to its unfunctionalized counterpart using in situ second harmonic
      generation measurements. Whereas the nonpolar liquid n-hexane did not induce any
      surface dynamic processes in the ionomer under study, the presence of water
      initiated a Debye-type dynamic reaction at the surface of the PC ionomer, which
      had no equivalent in the unfunctionalized material. This first-order reaction was
      attributed to a surface enrichment process of the functionalized ionomer in the
      hydrophilic environment involving movement of the PC endgroups from aggregates in
      the bulk to the surface. The time constant of the process was found to be about 6
      min, and the corresponding activation energy was 0.4 eV. The dehydration process
      of the PC-functionalized ionomer in nitrogen gas atmosphere could be described by
      two time constants, one slightly below 1 min and the other one just above 13 min.
      The results presented in this work show that SHG measurements are well suited for
      the study of polymer surface restructuring dynamics in response to environmental
      changes. Such information is very important for the successful design and
      implementation of biomimetic polymers intended for biomedical applications.

PMID- 18717535
TI  - Kinetic-dynamic model for conformational control of an electron transfer
      photocycle: mixed-metal hemoglobin hybrids.
AB  - It is becoming increasingly clear that the transfer of an electron across a
      protein-protein interface is coupled to the dynamics of conformational conversion
      between and within ensembles of interface conformations. Electron transfer (ET)
      reactions in conformationally mobile systems provide a "clock" against which the
      rapidity of a dynamic process may be measured, and we here report a simple
      kinetic (master equation) model that self-consistently incorporates
      conformational dynamics into an ET photocycle comprised of a photoinitiated
      "forward" step and thermal return to ground. This kinetic/dynamic (KD) model
      assumes an ET complex exists as multiple interconverting conformations which
      partition into an ET-optimized (reactive; R) population and a less-reactive
      population ( S). We take the members of each population to be equivalent by
      constraining them to have the same conformational energy, the same average rate
      constant for conversion to members of the other population, and the same rate
      constants for forward and back ET. The result is a mapping of a complicated
      energy surface onto the simple "gating", two-well surface, but with rate
      constants that are defined microscopically. This model successfully describes the
      changes in the ET photocycle within the "predocked" mixed-metal hemoglobin (Hb)
      hybrid, [alpha(Zn), beta(Fe3+N 3 (-))], as conformational kinetics are modulated
      by variations in viscosity (eta = 1-15 cP; 20 degrees C). The description reveals
      how the conformational "routes" by which a hybrid progresses through a photocycle
      differ in different dynamic regimes. Even at eta = 1 cP, the populations are not
      in fast exchange, and ET involves a complex interplay between conformational and
      ET processes; at intermediate viscosities the hybrid exhibits "differential
      dynamics" in which the forward and back ET processes involve different initial
      ensembles of configurational substates; by eta = 15 cP, the slow-exchange limit
      is approached. Even at low viscosity, the ET-coupled motions are fairly slow,
      with rate constants of <10 (3) s (-1). Current ideas about Hb function lead to
      the testable hypothesis that ET in the hybrid may be coupled to allosteric
      fluctuations of the two [alpha 1, beta 2] dimers of Hb.

PMID- 18717536
TI  - Cellular uptake and intracellular pathways of PLL-g-PEG-DNA nanoparticles.
AB  - Polycationic molecules form condensates with DNA and are used for gene therapy as
      an alternative to viral vectors. As clinical efficacy corresponds to cellular
      uptake, intracellular stability of the condensates, and bioavailability of the
      DNA, it is crucial to analyze uptake mechanisms and trafficking pathways. Here, a
      detailed study of uptake, stability, and localization of PLL-g-PEG-DNA
      nanoparticles within COS-7 cells is presented, using FACS analysis to assess the
      involvement of different uptake mechanisms, colocalization studies with markers
      indicative for different endocytotic pathways, and immunofluorescence staining to
      analyze colocalization with intracellular compartments. PLL-g-PEG-DNA
      nanoparticles were internalized in an energy-dependent manner after 2 h and
      accumulated in the perinuclear region after >6 h. The nanoparticles were found to
      be stable within the cytoplasm for at least 24 h and did not colocalize with the
      endosomal pathway. Nanoparticle uptake was approximately 50% inhibited by
      genistein, an inhibitor of the caveolae-mediated pathway. However, genistein did
      not inhibit gene expression, and PLL-g-PEG-DNA nanoparticles were not colocalized
      with caveolin-1 indicating that caveolae-mediated endocytosis is not decisive for
      DNA delivery. Clathrin-mediated endocytosis and macropinocytosis pathways were
      reduced by 17 and 24%, respectively, in the presence of the respective
      inhibitors. When cells were transfected in the presence of double and triple
      inhibitors, transfection efficiencies were increasingly reduced by 40 and 70%,
      respectively; however, no differences were found between the different uptake
      mechanisms. These findings suggest that PLL-g-PEG-DNA nanoparticles enter by
      several pathways and might therefore be an efficient and versatile tool to
      deliver therapeutic DNA.

PMID- 18717537
TI  - Hyaluronan-tethered opioid depots: synthetic strategies and release kinetics in
      vitro and in vivo.
AB  - We proposed the use of opioid drug bound covalently to hyaluronan (HA) via ester
      linkages as a method to prolong drug delivery and to possibly increase the
      quality of perioperative pain management. The in vitro release profile of
      morphine conjugated to HA (1.3 million MW) was studied. The influence of
      parameters such as conjugation site and steric protection of the labile ester
      bonds was investigated in phosphate buffered saline (PBS) medium. HA--codeine and
      HA--naloxone conjugates were used as structural controls. Codeine and morphine
      conjugated via the allylic hydroxyl group had a release half-life of 14.0 days in
      PBS. Naloxone conjugated via the phenolic hydroxyl group showed a half-life of
      0.3 days, and all drugs admixed in HA showed half-lives of 0.1 days. Methyl,
      ethyl, or n-propyl introduced in vicinal position to the ester bond prolonged
      release of naloxone with half-lives of 0.5, 4.0, and 4.0 days in PBS,
      respectively. Incorporation of a methyl group prolonged codeine release with a
      half-life of 55.0 days in PBS. Drugs were released chemically unaltered from the
      conjugates as confirmed by LC-MS/MS. Further, morphine was conjugated to
      divinylsulfone cross-linked HA (Hylan B) particles and the release profiles in
      rat plasma were studied in vitro and in vivo. Release in rat plasma was faster
      than in PBS with a half-life of 2.5 days, but the release was similar (ca. 12
      days) when a cocktail of protease inhibitors was added to the plasma. Sustained
      release of morphine was observed in a rat surgical model over 30 h. Morphine was
      released chemically unaltered from the conjugate and morphine intermediates were
      not detected in significant amounts as confirmed by LC-MS/MS. These results
      suggest that the morphine release profile from the HA conjugates depends on the
      alkyl groups vicinal to the ester and the nature of the leaving group. In rat
      plasma, hydrolysis seems to be controlled by esterase activity.

PMID- 18717539
TI  - Kinetics and products of the gas-phase reactions of divinyl sulfoxide with OH and
      NO3 radicals and O3.
AB  - Using relative rate methods, rate constants for the gas-phase reactions of
      divinyl sulfoxide [CH 2CHS(O)CHCH 2; DVSO] with NO 3 radicals and O 3 have been
      measured at 296 +/- 2 K, and rate constants for the reaction with OH radicals
      have been measured over the temperature range of 277-349 K. Rate constants
      obtained for the NO 3 radical and O 3 reactions at 296 +/- 2 K were (6.1 +/- 1.4)
      x 10 (-16) and (4.3 +/- 1.0) x 10 (-19) cm (3) molecule (-1) s (-1),
      respectively. For the OH radical reaction, the temperature-dependent rate
      expression obtained was k = 4.17 x 10 (-12)e ((858 +/- 141)/ T ) cm (3) molecule
      (-1) s (-1) with a 298 K rate constant of (7.43 +/- 0.71) x 10 (-11) cm (3)
      molecule (-1) s (-1), where, in all cases, the errors are two standard deviations
      and do not include the uncertainties in the rate constants for the reference
      compounds. Divinyl sulfone was observed as a minor product of both the OH radical
      and NO 3 radical reactions at 296 +/- 2 K. Using in situ Fourier transform
      infrared spectroscopy, CO, CO 2, SO 2, HCHO, and divinyl sulfone were observed as
      products of the OH radical reaction, with molar formation yields of 35 +/- 11,
      2.2 +/- 0.8, 33 +/- 4, 54 +/- 6, and 5.4 +/- 0.8%, respectively, in air. For the
      experimental conditions employed, aerosol formation from the OH radical-initiated
      reaction of DVSO in the presence of NO was minor, being approximately 1.5%. The
      data obtained here for DVSO are compared with literature data for the
      corresponding reactions of dimethyl sulfoxide.

PMID- 18717540
TI  - Combined 3D-QSAR modeling and molecular docking study on indolinone derivatives
      as inhibitors of 3-phosphoinositide-dependent protein kinase-1.
AB  - 3-Phosphoinositide-dependent protein kinase-1 (PDK1) is a promising target for
      developing novel anticancer drugs. In order to understand the structure-activity
      correlation of indolinone-based PDK1 inhibitors, we have carried out a combined
      molecular docking and three-dimensional quantitative structure-activity
      relationship (3D-QSAR) modeling study. The study has resulted in two types of
      satisfactory 3D-QSAR models, including the CoMFA model (r(2)=0.907; q(2)=0.737)
      and CoMSIA model (r(2)=0.991; q(2)=0.824), for predicting the biological activity
      of new compounds. The detailed microscopic structures of PDK1 binding with
      inhibitors have been studied by molecular docking. We have also developed docking
      based 3D-QSAR models (CoMFA with q(2)=0.729; CoMSIA with q(2)=0.79). The contour
      maps obtained from the 3D-QSAR models in combination with the docked binding
      structures help to better interpret the structure-activity relationship. All of
      the structural insights obtained from both the 3D-QSAR contour maps and molecular
      docking are consistent with the available experimental activity data. This is the
      first report on 3D-QSAR modeling of PDK1 inhibitors. The satisfactory results
      strongly suggest that the developed 3D-QSAR models and the obtained PDK1
      inhibitor binding structures are reasonable for the prediction of the activity of
      new inhibitors and in future drug design.

PMID- 18717541
TI  - Nature of water transport and electro-osmosis in nafion: insights from first
      principles molecular dynamics simulations under an electric field.
AB  - The effects of water content on water transport and electro-osmosis in a
      representative polymer electrolyte membrane, Nafion, are investigated in detail
      by means of first-principles molecular dynamics (MD) simulations in the presence
      of a homogeneous electric field. We have directly evaluated electro-osmotic drag
      coefficients (the number of water molecules cotransported with proton conduction)
      from the trajectories of the first-principles MD simulations and also explicitly
      evaluated factors that contribute to the electro-osmotic drag coefficients. In
      agreement with previously reported experiments, our calculations show virtually
      constant values ( approximately 1) of the electro-osmotic drag coefficients for
      both low and high water content states. Detailed comparisons of each factor
      contributing to the drag coefficient reveal that an increase in water content
      increases the occurrence of the Grotthuss-like effective proton transport
      process, whose contribution results in a decrease in the electro-osmotic drag
      coefficient. At the same time, an environment that is favorable for the Grotthuss
      like effective proton transport process is also favorable for the transport of
      water arising from water transport occurring beyond the hydration shell around
      the protons, whose contribution results in an increase in the electro-osmotic
      drag coefficient. Conversely, an environment that is not favorable for proton
      conduction is also not favorable for water transport. As a result, the electro
      osmotic drag coefficient shows virtually identical values with respect to change
      in the water content.

PMID- 18717542
TI  - Hyperbranched ferrocenyl polymer film with high charge transport efficiency.
AB  - The electrochemical behaviors of hyperbranched poly(ferrocenyl-methylsilane)
      (HPFMS) and linear oligo(ferrocenyldimethylsilane) (LOFS) films were studied
      systematically by cyclic voltammetry and chronocoulometry under different polymer
      coverage and solvents. Both poly(ferrocenylsilanes) show stable cyclic
      voltammographs in LiClO 4 solutions. Compared with LOFS films, HPFMS films
      exhibit higher charge transport efficiency because of their hyperbranched
      structure: peak current ( i p) and apparent diffusion coefficient ( D app) for
      HPFMS films are larger than those for LOFS films, especially at high polymer
      coverage (3.8 x 10 (-11) vs 3.9 x 10 (-12) cm2/s for HPFMS and LOFS film at the
      coverage of 2.1 x 10 (-6) mol Fc/cm2). The conceptual models of electrode
      processes for HPFMS and LOFS films were proposed to account for higher charge
      transport efficiency of HPFMS films. It is also found that a solvent with the
      appropriate solubility parameter and polarity, lower viscosity, and higher
      dielectric constant is in favor of charge transport through polymer films, which
      is consistent with the proposed model of electrode process for HPFMS films. These
      results imply that hyperbranched ferrocenyl polymers have the potential to be
      excellent chemical sensor materials with convenient synthesis and high
      sensitivity.

PMID- 18717543
TI  - Estimation of the persistence length of DNA from the torsion elastic constant and
      supercoiling free energy: effect of ethylene glycol.
AB  - Two different methods are proposed to estimate the persistence length ( P) of DNA
      from the measured torsion elastic constant (alpha) and the twist energy parameter
      ( E T ) that governs the supercoiling free energy. The first method involves
      Monte Carlo simulations and reversible-work calculations of E T for model DNAs
      that possess the measured alpha and selected trial values of P. Comparison of the
      computed E T values with the experimental value allows estimation of P (or
      equivalently the bending elastic constant (kappa beta)) by interpolation. A far
      simpler, though less accurate, alternative is to solve a previously conjectured
      analytical relation connecting E T , alpha, kappa beta (or P), and an unknown
      "constant" ( B). The present simulations are used to ascertain the optimum value
      of B and to assess the validity and accuracy of that relation. Within the
      simulation errors, P values obtained from the measured alpha and E T via this
      analytical expression agree with those determined from the simulations and E T
      values reckoned from the input alpha and kappa beta by this analytical expression
      agree with the corresponding simulated values. Although B is found to be
      insensitive to variation in alpha, it appears to decline slightly with increasing
      kappa beta. The original analytical expression is modified to take this apparent
      variation of B with kappa beta into account. By using this modified analytical
      relation to estimate P (from the measured alpha and E T ) or E T (from the input
      alpha and kappa beta), much closer agreement is obtained respectively with the
      values of P or E T obtained from the simulations. As specific examples, these
      methods are applied to determine P in 0 and 20 w/v % ethylene glycol, which has
      been shown to induce a structural transition in duplex DNA.

PMID- 18717544
TI  - Interaction and structure of surfaces coated by poly(vinyl amines) of different
      line charge densities.
AB  - Interactions between preadsorbed films of poly(vinyl amine) (PVA) of two
      different line charge densities on silica substrates were studied with the
      colloidal probe technique based on the atomic force microscope (AFM). The
      preadsorbed films were prepared by adsorption of PVA from a pH 4 solution without
      any added salt. The highly charged PVA adsorbs in a flat configuration and in
      laterally heterogeneous layers, while the more weakly charged PVA analog adsorbs
      in thicker and more homogeneous films. As revealed by reflectivity measurements,
      such preadsorbed PVA films are stable in polyelectrolyte-free solutions. However,
      force measurements with the colloidal probe reveal that their interactions depend
      strongly on the ionic strength. Upon approach, interactions are dominated by
      electrostatic diffuse layer overlap forces. Both PVA films have very similar
      diffuse layer charge densities of about 1.5 mC/m2. Since these values are
      substantially lower than what would be expected from the total charge of the
      adsorbed polyelectrolytes measured by reflectivity, we infer that coadsorption of
      anions represents the principal mechanism in charge neutralization. Upon
      retraction, the adhesion between the films is dominated by bridging forces due to
      single polymer chains. Such bridging adhesion becomes progressively important
      with increasing ionic strength, whereby their range and frequency increase. The
      work of adhesion due to bridging is about 0.3 mN/m. At low ionic strengths, the
      films behave differently. While the highly charged PVA shows unspecific adhesion
      at small distances, the more weakly charged PVA analog shows few adhesion events
      occurring at long distances.

PMID- 18717546
TI  - Conjugating luminescent CdTe quantum dots with biomolecules.
AB  - Newly prepared CdTe quantum dots ( QD) bearing shells of water solubility
      providing capping agents (i.e., thioglycolic acid ( TGA) and 2
      (dimethylamino)ethanethiol hydrochloride (DMAET) were subjected to electrostatic
      assays with several proteins (i.e., cytochrome c (cyt c) and human serum albumin
      (HSA). In particular, we employed absorption, emission, transient absorption and
      time-resolved emission spectroscopic means to test their response to light. Only
      for negatively capped QDs spectroscopic and kinetic evidence were gathered that
      corroborate the successful bioconjugation of QDs with cyt c to yield QD- cyt c
      bioconjugates. In fact, photoexcitation of QD-cyt c leads to a fast deactivation
      of the QD band gap emission and of the QD excited state. Notably, these
      interactions depend on the size of the QDs. Repulsive forces, on the other hand,
      are operative between the positively capped QDs and cyt c, hampering any
      bioconjugation.

PMID- 18717547
TI  - PEO-[M(CN)5NO](x-) (M = Fe, Mn, or Cr) interaction as a driving force in the
      partitioning of the pentacyanonitrosylmetallate anion in ATPS: strong effect of
      the central atom.
AB  - The partitioning behavior of pentacyanonitrosilmetallate complexes[Fe(CN) 5 NO]
      (2-), [Mn(CN) 5 NO] 3(-), and [Cr(CN) 5 NO] 3(-)has been studied in aqueous two
      phase systems (ATPS) formed by adding poly(ethylene oxide) (PEO; 4000 g mol (-1))
      to an aqueous salt solution (Li2 SO4, Na2 SO4, CuSO4, or ZnSO4). The complexes
      partition coefficients ( K complex) in each of these ATPS have been determined as
      a function of increasing tie-line length (TLL) and temperature. Unlike the
      partition behavior of most ions, [Fe(CN) 5 NO] 2(-) and [Mn(CN) 5 NO] 3(-) anions
      are concentrated in the polymer-rich phase with K values depending on the nature
      of the central atom as follows: K [Fe(C N) 5 NO] 2 - >> K [ Mn (CN 5 NO] 3 - > K
      [C r (C N) 5 NO ]3 - . The effect of ATPS salts in the complex partitioning
      behavior has also been verified following the order Li2 SO 4 > Na2 SO 4 > ZnSO4.
      Thermodynamic analysis revealed that the presence of anions in the polymer-rich
      phase is caused by an EO-[M(CN) 5 NO] ( x- ) (M = Fe, Mn, or Cr) enthalpic
      interaction. However, when this enthalpic interaction is weak, as in the case of
      the [Cr(CN) 5 NO]3(-) anion ( K [Cr(CN 5 NO] 3 - < 1), entropic driving forces
      dominate the transfer process, then causing the anions to concentrate in the salt
      rich phase.

PMID- 18717545
TI  - Raman spectroscopy reveals direct chromophore interactions in the Leu/Gln105
      spectral tuning switch of proteorhodopsins.
AB  - Proteorhodopsins are an extensive family of photoactive membrane proteins found
      in proteobacteria distributed throughout the world's oceans which are often
      classified as green- or blue-absorbing (GPR and BPR, respectively) on the basis
      of their visible absorption maxima. GPR and BPR have significantly different
      properties including photocycle lifetimes and wavelength dependence on pH.
      Previous studies revealed that these different properties are correlated with a
      single residue, Leu105 in GPR and Gln105 in BPR, although the molecular basis for
      the different properties of GPR and BPR has not yet been elucidated. We have
      studied the unexcited states of GPR and BPR using resonance Raman spectroscopy
      which enhances almost exclusively chromophore vibrations. We find that both
      spectra are remarkably similar, indicating that the retinylidene structure of GPR
      and BPR are almost identical. However, the frequency of a band assigned to the
      retinal C13-methyl-rock vibration is shifted from 1006 cm (-1) in GPR to 1012 cm
      (-1) in BPR. A similar shift is observed in the GPR mutant L105Q indicating Leu
      and Gln residues interact differently with the retinal C13-methyl group. The
      environment of the Schiff base of GPR and BPR differ as indicated by differences
      in the H/D induced down-shift of the Schiff base vibration. Residues located in
      transmembrane helices (D-G) do not contribute to the observed differences in the
      protein-chromophore interaction between BPR and GPR based on the Raman spectra of
      chimeras. These results support a model whereby the substitution of the
      hydrophilic Gln105 in BPR with the smaller hydrophobic Leu105 in GPR directly
      alters the environment of both the retinal C13 group and the Schiff base.

PMID- 18717548
TI  - 31P NMR investigation of backbone dynamics in DNA binding sites.
AB  - The backbone conformation of DNA plays an important role in the indirect readout
      mechanisms for protein--DNA recognition events. Thus, investigating the backbone
      dynamics of each step in DNA binding sequences provides useful information
      necessary for the characterization of these interactions. Here, we use 31P
      dynamic NMR to characterize the backbone conformation and dynamics in the
      Dickerson dodecamer, a sequence containing the EcoRI binding site, and confirm
      solid-state 2H NMR results showing that the C3pG4 and C9pG10 steps experience
      unique dynamics and that these dynamics are quenched upon cytosine methylation.
      In addition, we show that cytosine methylation affects the conformation and
      dynamics of neighboring nucleotide steps, but this effect is localized to only
      near neighbors and base-pairing partners. Last, we have been able to characterize
      the percent BII in each backbone step and illustrate that the C3pG4 and C9pG10
      favor the noncanonical BII conformation, even at low temperatures. Our results
      demonstrate that 31P dynamic NMR provides a robust and efficient method for
      characterizing the backbone dynamics in DNA. This allows simple, rapid
      determination of sequence-dependent dynamical information, providing a useful
      method for studying trends in protein-DNA recognition events.

PMID- 18717549
TI  - Mechanical stability of micropipet-aspirated giant vesicles with fluid phase
      coexistence.
AB  - Micropipet aspiration of phase-separated lipid bilayer vesicles can elucidate
      physicochemical aspects of membrane fluid phase coexistence. Recently, we
      investigated the composition dependence of line tension at the boundary between
      liquid-ordered and liquid-disordered phases of giant unilamellar vesicles
      obtained from ternary lipid mixtures using this approach. Here we examine
      mechanical equilibria and stability of dumbbell-shaped vesicles deformed by line
      tension. We present a relationship between the pipet aspiration pressure and the
      aspiration length in vesicles with two coexisting phases. Using a strikingly
      simple mechanical model for the free energy of the vesicle, we predict a relation
      that is in almost quantitative agreement with experiment. The model considers the
      vesicle free energy to be proportional to line tension and assumes that the
      vesicle volume, domain area fraction, and total area are conserved during
      aspiration. We also examine a mechanical instability encountered when releasing a
      vesicle from the pipet. We find that this releasing instability is observed
      within the framework of our model that predicts a change of the compressibility
      of a pipet-aspirated membrane cylinder from positive (i.e., stable) to negative
      (unstable) values, at the experimental instability. The model furthermore
      includes an aspiration instability that has also previously been experimentally
      described. Our method of studying micropipet-induced shape transitions in giant
      vesicles with fluid domains could be useful for investigating vesicle shape
      transitions modulated by bending stiffness and line tension.

PMID- 18717550
TI  - Rheological study on rapid recovery of hydrogel based on oligomeric electrolyte.
AB  - The hydrogel consisting of an oligomeric electrolyte, poly[pyridinium-1,4-diyl
      iminocarbonyl-1,4-phenylenemethylene chloride] (1-Cl) underwent self-healing at
      temperatures lower than its gelation temperature after destruction of the gel
      network in a shear flow. The self-healing mechanism was investigated by
      rheological measurements on three different kinds of gels including a low
      molecular weight organogelator and a polymeric hydrogelator. Although all of the
      three gels exhibited thermo-reversible hysteresis loops in the shear moduli, only
      1-Cl hydrogel recovered its mechanical properties after vigorous agitation. It is
      conjectured that the self-healing is due to formation of network structure via a
      chlorine ion mediated hydrogen bond for which the activation energy is on the
      order of 10 kJ/mol.

PMID- 18717551
TI  - Heterocyclic diamidine interactions at AT base pairs in the DNA minor groove:
      effects of heterocycle differences, DNA AT sequence and length.
AB  - Given the increasing significance of diamidines as DNA-targeted therapeutics and
      biotechnology reagents, it is important to establish the variations in
      thermodynamic quantities that characterize the interactions of closely related
      compounds to different sequence AT binding sites. In this study, an array of
      methods including biosensor-surface plasmon resonance (SPR), isothermal titration
      microcalorimetry (ITC), circular dichroism (CD), thermal melting (Tm) and
      molecular modeling have been used to characterize the binding of dicationic
      diamidines related to DB75 (amidine-phenyl-furan-phenyl-amidine) with alternating
      and nonalternating AT sequences. Conversion of the central furan of DB75 to other
      similar groups, such as thiophene or selenophene, can yield compounds with
      increased affinity and sequence binding selectivity for the minor groove.
      Calorimetric measurements revealed that the thermodynamic parameters (Delta G,
      Delta H, Delta S) that drive diamidine binding to alternating and nonalternating
      oligomers can be quite different and depend on both DNA sequence and length.
      Small changes in a compound can have major effects on DNA interactions. By
      choosing an appropriate central group it is possible to "tune" the shape of the
      molecule to match DNA for enhanced affinity and sequence recognition.

PMID- 18717552
TI  - Observation of singlet cycloreversion of thymine oxetanes by direct photolysis.
AB  - An ultrafast broadband transient absorption spectroscopic study of the direct
      photolysis of oxetane DMT-BP [which is the oxetane adduct of 1,3-dimethylthymine
      (DMT) with benzophenone (BP)] is presented. Previous nanosecond time-resolved
      absorption studies by other researchers observed that direct photolysis of such
      oxetanes results in a rare, adiabatic photochemical reaction to produce a triplet
      excited-state carbonyl species. However, the mechanism for this adiabatic
      photochemical reaction remained unclear for the reaction sequence of the bond
      scission and the intersystem crossing (ISC) because of the time resolution for
      the experiments, and this prompted us to further study its mechanism with
      ultrafast time-resolution. The ultrafast time-resolved spectra presented here
      indicate that the cycloreversion reaction occurs in a stepwise manner on a
      singlet excited-state, and then intersystem crossing (ISC) occurs to produce the
      triplet carbonyl product observed in the previously reported nanosecond time
      resolved experiments.

PMID- 18717553
TI  - Dynamic structure of regioregulated poly(alkylthiophene)s.
AB  - Solid-state structures of regioregulated poly(3-hexylthiophene) (P3HT) and poly(3
      butylthiophene) (P3BT) were investigated using Fourier transform infrared
      absorption (FT-IR) spectroscopy. This study revealed that a twist glass
      transition of thiophene twisting for P3HT exists around 300 K ( T gp).
      Additionally, the influence of annealing on population of glassy crystal,
      crystal, and plastic crystal phases was explored. The annealed sample is
      dominated by plastic crystal phase, and this phase increases with annealing
      temperature below T gp. The frustration against crystallization in P3HT is weaker
      than that in P3BT. Consequently, the plastic crystal phase is formed as a
      dominant structure, whereas P3BT forms both a well-defined crystal in the
      conventional sense and glassy crystal.

PMID- 18717554
TI  - Electrochemical and spectroscopic behavior of iron(III) porphyrazines in Langmuir
      Schafer films.
AB  - Thin films of a newly synthesized iron(III) porphyrazine, LFeOESPz ( L = ClEtO,
      OESPz = ethylsulfanylporphyrazine), have been deposited by the Langmuir-Schafer
      (LS) technique (horizontal lifting) on ITO or gold substrates. Before deposition,
      the floating films have been investigated at the air-water interface by
      pressure/area per molecule (pi/ A) experiments, Brewster angle microscopy (BAM)
      and UV-vis reflection spectroscopy (RefSpec). The complex reacts with water
      subphase (pH 6.2) forming the mu-oxo dimer, which becomes the predominant
      component of the LS films ( LS-Fe) as indicated by optical, IR, XPS, and
      electrochemical data. LS-Fe multilayers exhibit, between open circuit potential
      (OCP) and +0.90 V (vs SCE), two independent peak pairs with formal potentials, E
      surf (I) and E surf(II) of +0.56 V and +0.78 V, respectively. According to
      dynamic voltammetric and coulometric experiments the peak pair at +0.56 V is
      attributed to one-electron process at the iron(III) centers on the monomer, while
      the peak pair at +0.78 V is associated to a four-electron process involving mu
      oxo-dimer oligomers. LS-Fe films prove to be quite stable electrochemically
      between OCP and +0.90 V. The electrochemical stability decreases, however, when
      the potential range is extended both anodically and cathodically outside these
      limits, due to formation of new species. Upon incubation with TCA solutions, LS
      Fe films show remarkable changes in the UV-vis spectra, which are consistent with
      a significant mu-oxo dimer --> monomer conversion. Addition of TCA to the
      electrochemical cell using a LS-Fe film as working electrode, results in a linear
      increase of a cathodic current peak near -0.40 V as the TCA concentration varies
      in the 0.1-2.0 mM range. This behavior is interpreted in terms of TCA inducing a
      progressive change in the composition of the LS-Fe films in favor of the
      monomeric iron(III) porphyrazine, which is responsible for the observed increase
      in the cathodic current near -0.40 V.

PMID- 18717555
TI  - Structural and vibrational characterization of polyaniline nanofibers prepared
      from interfacial polymerization.
AB  - This work deals with the structural and vibrational characterization of PANI
      nanofibers prepared through interfacial polymerization using different
      concentrations of HCl aqueous solution. The results were compared to those
      obtained by PANI prepared through the conventional route. X-ray diffraction and
      small-angle X-ray scattering techniques showed that high concentrations of HCl
      solutions used in the preparation of the PANI nanofibers reduce their
      crystallinity. The increase of regions with granular morphology was also observed
      in the scanning electron microscopy images. The changes in the resonance Raman
      spectra from 200 to 500 cm (-1), FTIR spectra, and the EPR data of the PANI
      nanofibers reveal an increase in the torsion angles of C ring-N-C ring segments
      owing the formation of bipolarons in the PANI backbone higher than the PANI
      samples prepared by conventional route.

PMID- 18717556
TI  - Thermodynamics of micellization of beta-sheet forming poly(acrylic acid)-block
      poly(l-valine) hybrids.
AB  - The phase behavior and thermodynamic of micellization of three hybrid
      poly(acrylic acid)- block-poly( l-valine), namely PAA 40-b-PLVAL 100, PAA 80-b
      PLVAL 100, and PAA 80-b-PLVAL 80, were investigated. beta-sheet formation in
      these polymeric systems resulted in a dominant enthalpic micellization process
      that exhibited an upper critical solution temperature (UCST). Micelle
      dissociation at higher temperatures is attributed to the disruption of favorable
      hydrogen bonds in the micellar core. Separation of hydrogen bond contributions to
      the micellization thermodynamics through the addition of urea as an external
      denaturing agent, revealed a shift from a dominant enthalpic contribution of
      PLVAL segments at low degree of deprotonation (alpha), where significant beta
      sheet is formed, to a balanced enthalpy and entropy contributions at high alpha.
      At high alpha, an enhanced "water cage" hydration of unimers was observed due to
      the formation of water-PLVAL hydrogen bonds. Hydrophobic forces played an
      indirect role in enhancing the compactness of the hydrophobic core, which
      enhanced the strength of hydrogen bonds in the beta-sheet structures.

PMID- 18717557
TI  - The mechanism of long-range exciton diffusion in a nematically organized
      porphyrin layer.
AB  - The exciton diffusion length in a nematically organized meso-tetra(4-n
      butylphenyl)porphyrin (TnBuPP) layer was found to exceed 40 nm at a temperature
      of 90 K and to be equal to 22 +/- 3 nm at 300 K. The exciton diffusion
      coefficient decreases from > or = 3.1 x 10(-6) m(2)/s at 90 K to (2.5 +/- 0.5) x
      10(-7) m(2)/s at 300 K. This thermal deactivation is attributed to exciton motion
      via a band mechanism. The motion of an exciton is not limited by polaronic
      effects; that is, the deformation of the atomic lattice around the exciton. The
      absence of polaronic self-trapping implies that the exciton diffusion coefficient
      can be enhanced by improvement of structural order and rigidity of the material.

PMID- 18717558
TI  - Formation of secondary triplet species after excitation of fluoroquinolones in
      the presence of relatively strong bases.
AB  - Laser flash photolysis of 7-(piperazin-1-yl) fluoroquinolones leads to the
      formation of a triplet excited state (3A*) at the end of the pulse (lambdamax
      520, 610, and 620 nm for enoxacin, ciprofloxacin, and norfloxacin, respectively).
      Phosphate and bicarbonate buffers react with 3A* to form a secondary triplet
      (3B*, reaction rates (0.8-9.9) x 108 M-1 s-1), whose T-T absorption is red
      shifted (lambdamax 670 nm for enoxacin, 700 nm for ciprofloxacin and
      norfloxacin). The formation of a secondary triplet is not a common process and
      disagrees with previous work suggesting that electron transfer occurs between
      phosphate buffer and the primary triplet excited state with the formation of the
      anion radical of the fluoroquinolone (FQ.-). We have shown that the FQ.-
      transient absorption spectrum is quite distinct from that of 3B*. The
      photophysical characteristics of 3B* have been determined by energy transfer to
      naproxen, and it has been found that its energy is lower than that of 3A*.

PMID- 18717559
TI  - Residual ligand entropy in the binding of p-substituted benzenesulfonamide
      ligands to bovine carbonic anhydrase II.
AB  - In studies on the thermodynamics of ligand-protein interactions, it is often
      assumed that the configurational and conformational entropy of the ligand is zero
      in the bound state (i.e., the ligand is rigidly fixed in the binding pocket).
      However, there is little direct experimental evidence for this assumption, and in
      the case of binding of p-substituted benzenesulfonamide inhibitors to bovine
      carbonic anhydrase II (BCA II), the observed thermodynamic binding signature
      derived from isothermal titration calorimetry experiments leads indirectly to the
      conclusion that a considerable degree of residual entropy remains in the bound
      ligand. Specifically, the entropy of binding increases with glycine chain length
      n, and strong evidence exists that this thermodynamic signature is not driven by
      solvent reorganization. By use of heteronuclear (15)N NMR relaxation measurements
      in a series (n = 1-6) of (15)N-glycine-enriched ligands, we find that the
      observed thermodynamic binding signature cannot be explained by residual ligand
      dynamics in the bound state, but rather results from the indirect influence of
      ligand chain length on protein dynamics.

PMID- 18717560
TI  - Temperature-dependent interconversion of phosphoramidite-Cu complexes detected by
      combined diffusion studies, 31P NMR, and low-temperature NMR spectroscopy.
AB  - For copper-catalyzed enantioselective conjugate additions, knowledge about the
      precatalytic and catalytic complexes has not yet been sufficiently developed to
      understand the strong influence of different temperatures on these famous
      reactions. Therefore, NMR experiments with four Cu(I) salts and two
      phosphoramidite ligands have been performed to elucidate the temperature
      dependence and the low-temperature structures of these copper complexes. The
      existence of the precatalytic binuclear complex with a mixed trigonal/tetrahedral
      coordination on copper is for the first time proven with direct NMR spectroscopic
      methods. Below 200 K, intermolecular interactions between free ligands and
      [Cu2X2L3] complexes induce binuclear [Cu2X2L4] complexes similar to the crystal
      structures. By combining diffusion experiments and (31)P integrals at different
      temperatures, it is for the first time possible to follow the formation of
      stoichiometrically different complexes, even under experimental conditions in
      which the (31)P signals of the complexes are spectroscopically not resolved due
      to exchange processes. This allows a first correlation between the complex
      species observed and the synthetic conditions reported. Furthermore, different
      preferences to build homo- or heterochiral complexes are detected for binaphthol
      and biphenol phosphoramidite complexes.

PMID- 18717561
TI  - Early homogenous amorphous precursor stages of calcium carbonate and subsequent
      crystal growth in levitated droplets.
AB  - An in situ study of the contact-free crystallization of calcium carbonate in
      acoustic levitated droplets is reported. The levitated droplet technique allows
      an in situ monitoring of the crystallization while avoiding any foreign phase
      boundaries that may influence the precipitation process by heterogeneous
      nucleation. The diffusion-controlled precipitation of CaCO3 at neutral pH starts
      in the initial step with the homogeneous formation of a stable, nanosized liquid
      like amorphous calcium carbonate phase that undergoes in a subsequent step a
      solution-assisted transformation to calcite. Cryogenic scanning electron
      microscopy studies indicate that precipitation is not induced at the solution/air
      interface. Our findings demonstrate that a liquid-liquid phase separation occurs
      at the outset of the precipitation under diffusion-controlled conditions (typical
      for biomineral formation) with a slow increase of the supersaturation at neutral
      pH.

PMID- 18717562
TI  - Hysteresis in the physisorption of CO2 and N2 in a flexible pillared layer nickel
      cyanide.
AB  - Rare hysteretic adsorption/desorption isotherms are reported for CO2 and N2 on a
      pillared Ni(1,2-bis(4-pyridyl)ethylene)[Ni(CN)4] compound (NiBpeneNiCN). The
      hysteresis occurs under moderate pressure and at temperatures above the critical
      temperatures of the respective gases. Powder X-ray diffraction measurements
      indicate that the material is an extended three-dimensional analogue of the well
      known Hofmann clathrates which is formed through axial bridging of the in-plane
      octahedral Ni sites by the bidentate 1,2-bis(4-pyridyl)ethylene. The hysteretic
      behavior toward guest adsorption and desorption is attributed to a structural
      phase transition in the material resulting from a variation in the tilt angle of
      the 1,2-bis(4-pyridyl)ethylene pillars. Kinetics studies on the desorption of
      acetone from the material show two first-order processes with two rate constants
      yielding activation energies of 68 and 55 kJ/mol when loadings are greater than 1
      equiv of acetone per formula unit. The CO2 adsorption/desorption isotherms on the
      series of structurally similar Ni(L)[Ni(CN)4] compounds, where L = pyrazine, 4,4'
      bipyridine, 1,2-bis(4-pyridyl)ethane, and dipyridylacetylene, are also reported.
      In contrast to NiBpeneNiCN, the rigid members of this series show normal type I
      isotherms with no measureable hysteresis and no significant structural changes
      during the adsorption/desorption cycle, while the flexible 1,2-bis(4
      pyridyl)ethane-bridged sample collapses in the guest-free state and shows no
      significant adsorption of CO2.

PMID- 18717563
TI  - Stereoselective dichlorination of allylic alcohol derivatives to access key
      stereochemical arrays of the chlorosulfolipids.
AB  - Dichlorination of (Z)-allylic trichloroacetates efficiently and stereoselectively
      generates the syn,syn hydroxydichloride stereotriad that is prevalent in the
      understudied polychlorinated sulfolipid class of natural products. Further, the
      dichlorination of a (Z)-allylic chlorohydrin affords with high selectivity a
      stereotetrad present in one of the chlorosulfolipids.

PMID- 18717564
TI  - Structure, magnetism, and theoretical study of a mixed-valence Co(II)3Co(III)4
      heptanuclear wheel: lack of SMM behavior despite negative magnetic anisotropy.
AB  - A mixed-valence Co(II)/Co(III) heptanuclear wheel [Co(II)3Co(III)4(L)6(MeO)6]
      (LH2 = 1,1,1-trifluoro-7-hydroxy-4-methyl-5-aza-hept-3-en-2-one) has been
      synthesized and its crystal structure determined using single-crystal X-ray
      diffraction. The valence state of each cobalt ion was established by bond valence
      sum calculations. Studies of the temperature dependence of the magnetic
      susceptibility and the field dependence of the magnetization evidence
      ferromagnetic interactions within the compound. In order to understand the
      magnetic properties of this Co7 wheel, we performed ab initio calculations for
      each cobalt fragment at the CASSCF/CASPT2 level, including spin-orbit coupling
      effects within the SO-RASSI approach. The four Co(III) ions were found to be
      diamagnetic and to give a significant temperature-independent paramagnetic
      contribution to the susceptibility. The spin-orbit coupling on the three Co(II)
      sites leads to separations of approximately 200 cm(-1) between the ground and
      excited Kramers doublets, placing the Co7 wheel into a weak-exchange limit in
      which the lowest electronic states are adequately described by the anisotropic
      exchange interaction between the lowest Kramers doublets on Co(II) sites.
      Simulation of the exchange interaction was done within the Lines model, keeping
      the fully ab initio treatment of magnetic anisotropy effects on individual cobalt
      fragments using a recently developed methodology. A good description of the
      susceptibility and magnetization was obtained for nearest-neighbor (J1) and next
      nearest-neighbor (J2) exchange parameters (1.5 and 5.5 cm(-1), respectively). The
      strong ferromagnetic interaction between distant cobalt ions arises as a result
      of low electron-promotion energies in the exchange bridges containing Co(III)
      ions. The calculations showed a large value of the magnetization along the main
      magnetic axis (10.1 mu(B)), which is a combined effect of the ferromagnetic
      exchange interaction and negative magnetic anisotropy on the two marginal Co(II)
      sites. The lack of single-molecule magnet behavior in [Co(II)3Co(III)4(L)6(MeO)6]
      is explained by relatively large matrix elements of transverse magnetic moments
      between states of maximal magnetization of the ground Kramers doublet, evidenced
      by ab initio calculations, and the associated large tunneling rates between these
      states in the presence of dipolar transverse magnetic fields in the crystal.

PMID- 18717566
TI  - Comparison of chemical and cell-based antioxidant methods for evaluation of foods
      and natural products: generating multifaceted data by parallel testing using
      erythrocytes and polymorphonuclear cells.
AB  - The objective of this study was to compare three tests frequently used for
      evaluation of antioxidant potential in natural products: (1) oxygen radical
      absorbance assay (ORAC), (2) cell-based antioxidant protection in an erythrocyte
      model (CAP-e), and (3) reactive oxygen species formation in polymorphonuclear
      cells (ROS PMN). The methods were applied to four natural products, all
      containing antioxidants capable of entering and protecting cells in the CAP-e
      assay. The magnitude of this effect was not directly correlated to the ORAC value
      of each product. Furthermore, the products showed different effects in the ROS
      PMN assay. Acai provided strong inhibition of ROS formation, indicating anti
      inflammatory properties. In contrast, Immunel and EpiCor mildly enhanced ROS
      formation, suggesting activation of the innate immune response. HA Joint Formula
      showed a complex, nonlinear dose-response in the ROS PMN assay. This illustrates
      that complex natural products may have similar antioxidant properties but
      different effects on human cells. Cell-based antioxidant protection is addressed
      best in the CAP-e assay, since some natural products contain compounds that may
      provoke cellular signaling in other cell types. The PMN cell type is a useful
      model for assessment of overall anti-inflammatory versus immune supportive
      properties of a product. The sequential use of the three methods serves to bridge
      analytical and biological testing methods.

PMID- 18717565
TI  - Chain dynamics of nascent polypeptides emerging from the ribosome.
AB  - Very little is known about the conformation of polypeptides emerging from the
      ribosome during protein biosynthesis. Here, we explore the dynamics of ribosome
      bound nascent polypeptides and proteins in Escherichia coli by dynamic
      fluorescence depolarization and assess the population of cotranslationally active
      chaperones trigger factor (TF) and DnaK. E. coli cell-free technology and
      fluorophore-linked E. coli Met-tRNA f Met enable selective site-specific labeling
      of nascent proteins at the N-terminal methionine. For the first time, direct
      spectroscopic evidence captures the generation of independent nascent chain
      motions for a single-domain protein emerging from the ribosome (apparent
      rotational correlation time approximately 5 ns), during the intermediate and late
      stages of polypeptide elongation. Such motions are detected only for a sequence
      encoding a globular protein and not for a natively unfolded control, suggesting
      that the independent nascent chain dynamics may be a signature of folding
      competent sequences. In summary, we observe multicomponent, severely rotationally
      restricted, and strongly chain length/sequence-dependent nascent chain dynamics.

PMID- 18717567
TI  - Assessment of radical scavenging capacity and lipid peroxidation inhibiting
      capacity of antioxidant.
AB  - The role of radical scavenging antioxidants against oxidative stress has received
      much attention, and the antioxidant capacity has been assessed by various
      methods. Among them, a method that measures the effect of antioxidant on decay of
      the probe is one of the most widely used methods. The present study was performed
      to compare the two methods to assess the antioxidant capacity, one to follow the
      decay of the probe and the other to measure lipid peroxidation products in human
      plasma. It was shown that the method following probe decay was suitable for
      assessment of radical scavenging capacity of antioxidant, but not for the
      capacity to inhibit lipid peroxidation in plasma. This is true whether a
      hydrophilic or lipophilic probe is used. Such different results arise from the
      fact that the efficacy of inhibition of lipid peroxidation by antioxidants
      depends on the fate of antioxidant-derived radical and interaction between
      antioxidants as well as the capacity of free radical scavenging. Thus, the
      capacity of antioxidants for inhibition of lipid peroxidation should be assessed
      from the effect on the extent of oxidation, not from the effect on probe decay.

PMID- 18717568
TI  - New investigation of the isothermal oxidation of extra virgin olive oil:
      determination of free radicals, total polyphenols, total antioxidant capacity,
      and kinetic data.
AB  - As a follow-up of the research programs carried out by our group concerning the
      artificial isothermal rancidification process in extra virgin olive oil (EVOO),
      in the present work the trends of both the total antioxidant capacity and the
      total polyphenols concentration as well as the main kinetic parameters of the
      process during the thermal oxidation of EVOO were studied and compared. In
      addition, the possibility of evaluating the increase in radicals concentration
      during the thermal oxidation process using a superoxide dismutase biosensor was
      also studied. The present investigation concerning this important food product is
      highly topical as it refers to the state of alteration of the EVOO used for
      cooking or frying, as a function of the temperature reached.

PMID- 18717569
TI  - In vitro and in vivo antioxidant and anti-inflammatory capacities of an
      antioxidant-rich fruit and berry juice blend. Results of a pilot and randomized,
      double-blinded, placebo-controlled, crossover study.
AB  - This study investigated the in vitro and in vivo antioxidant and anti
      inflammatory properties of a juice blend (JB), MonaVie Active, containing a
      mixture of fruits and berries with known antioxidant activity, including acai, a
      palm fruit, as the predominant ingredient. The phytochemical antioxidants in the
      JB are primarily in the form of anthocyanins, predominantly cyanidin 3-rutoside,
      cyanidin 3-diglycoside, and cyanidin 3-glucoside. The cell-based antioxidant
      protection of erythrocytes (CAP-e) assay demonstrated that antioxidants in the JB
      penetrated and protected cells from oxidative damage ( p < 0.001), whereas
      polymorphonuclear cells showed reduced formation of reactive oxygen species ( p <
      0.003) and reduced migration toward three different pro-inflammatory
      chemoattractants: fmlp ( p < 0.001), leukotriene B4 ( p < 0.05), and IL-8 ( p <
      0.03). A randomized, double-blinded, placebo-controlled, crossover trial with 12
      healthy subjects examined the JB's antioxidant activity in vivo. Blood samples at
      baseline, 1 h, and 2 h following consumption of the JB or placebo were tested for
      antioxidant capacity using several antioxidant assays and the TBARS assay, a
      measure of lipid peroxidation. A within subject comparison showed an increase in
      serum antioxidants at 1 h ( p < 0.03) and 2 h ( p < 0.015), as well as inhibition
      of lipid peroxidation at 2 h ( p < 0.01) postconsumption.

PMID- 18717570
TI  - Protective effects of standardized pomegranate (Punica granatum L.) polyphenolic
      extract in ultraviolet-irradiated human skin fibroblasts.
AB  - Exposure to ultraviolet (UV) radiation has been associated with several acute and
      chronic conditions, including sunburn, edema, hyperplasia, immunosuppression,
      photoaging, and skin cancer. The role of naturally occurring phytochemicals in
      the prevention of such UV-related conditions has captured increased interest.
      Pomegranate ( Punica granatum L.) is a rich source of polyphenolics, which have
      been shown to exert anti-inflammatory, antioxidant, and anticarcinogenic activity
      in numerous in vivo and in vitro studies. This work investigated potential
      protective effects of a pomegranate fruit extract standardized to punicalagins
      against UVA- and UVB-induced damage in SKU-1064 human skin fibroblast cells.
      Pomegranate extract (PE), in a range from 5 to 60 mg/L, was effective at
      protecting human skin fibroblasts from cell death following UV exposure, likely
      related to a reduced activation of the pro-inflammatory transcription factor NF
      kappaB, a downregulation of proapoptotic caspase-3, and an increased G0/G1 phase,
      associated with DNA repair. Higher polyphenolic concentrations (500-10000 mg/L)
      were needed to achieve a significant reduction in UV-induced reactive oxygen
      species levels and increased intracellular antioxidant capacity (from 1.9 to 8.6
      muM Trolox equivalents/mL). Results from this study demonstrate the protective
      effects of PE against UVA- and UVB-induced cell damage and the potential use of
      pomegranate polyphenolics in topical applications.

PMID- 18717571
TI  - Photostability of rebaudioside A and stevioside in beverages.
AB  - The Coca-Cola Company and Cargill, Inc. have initiated the development and
      commercialization of the Stevia rebaudiana (Bertoni) derived sweetener
      rebaudioside A. Efforts were focused on high purity rebaudioside A (>97% by
      HPLC), commonly known as rebiana. In the course of the development program,
      extensive stability studies were carried out on rebiana, all supporting good
      stability for use in all food and beverage applications, including conditions
      where rebiana-sweetened beverages were exposed to light. Our findings on rebiana
      light stability refute those of an earlier study that suggested rebaudioside A to
      be unstable to sunlight exposure, while the structurally homologous stevioside is
      stable. We replicated the earlier study and found no significant photodegradation
      for either rebaudioside A or stevioside.

PMID- 18717572
TI  - Chemical, molecular, and structural characterization of alkali extractable
      nonstarch polysaccharides from Job's tears.
AB  - The polished Job's tears ( Coix lachryma-jobi L.) seeds, dark and white husk
      types, were sequentially extracted by hot water (75 degrees C) and 0.5 M NaOH
      solution. Nonstarch polysaccharides were not found in the water extract but were
      present in the alkali extract. The major components of the alkali extract from
      both Job's tears were protein, ash, and nonstarch polysaccharides, mainly
      arabinoxylans. The high arabinose to xylose ratio of 1.25 and 1.24 indicated a
      highly substituted structure. The average molecular weight (MW) of arabinoxylans
      of the dark and white husk types were 741,000 Da (Pd 1.5) and 1,449,000 Da (Pd
      2.6), respectively, and their average MW reduced after treatment with protease.
      The alkali extractable arabinoxylans were elucidated to have a (1,4)-linked beta-
      d-xylan main chain highly substituted with single arabinose units. The results
      showed that the alpha- l-arabinofuranosyl residues (Ara f) were attached to the
      main chain mostly at O-3, followed by both O-2 and O-3 of xylopyranosyl residues
      (Xyl p).

PMID- 18717573
TI  - Interface of an array of five capillaries with an array of one-nanoliter wells
      for high-resolution electrophoretic analysis as an approach to high-throughput
      chemical cytometry.
AB  - We report a system that allows the simultaneous aspiration of one or more cells
      into each of five capillaries for electrophoresis analysis. A glass wafer was
      etched to create an array of 1-nL wells. The glass was treated with poly(2
      hydroxyethyl methacrylate) to control cell adherence. A suspension of formalin
      fixed cells was placed on the surface, and cells were allowed to settle. The
      concentration of cells and the settling time were chosen so that there was, on
      average, one cell per well. Next, an array of five capillaries was placed so that
      the tip of each capillary was in contact with a single well. A pulse of vacuum
      was applied to the distal end of the capillaries to aspirate the content of each
      well into a capillary. Next, the tips of the capillaries were placed in running
      buffer and potential was applied. The cells lysed upon contact with the running
      buffer, and fluorescent components were detected at the distal end of the
      capillaries by laser-induced fluorescence. The electrophoretic separation
      efficiency was outstanding, generating over 750,000 theoretical plates (1,800,000
      plates/m). In this example, AtT-20 cells were used that had been treated with TMR
      G(M1). The cells were allowed to metabolize this substrate into a series of
      products before the cells were fixed. The number of cells found in each well was
      estimated visually under the microscope and was described by a Poisson
      distribution with mean of 0.98 cell/well. This system provides an approach to
      high-throughput chemical cytometry.

PMID- 18717575
TI  - Influence of the dissolution rate on the collapse and shedding behavior of
      monostearin/monopalmitin-rich coated microbubbles.
AB  - A low cost food grade emulsifier (a mixture of monoglycerides, diglycerides, and
      sodium stearoyl lactylate) in combination with polyethylene glycol-40 stearate
      (PEG-40S) was used as an alternative to pure saturated phospholipids to form the
      thin shell of a microbubble. To investigate the stability of these microbubbles
      in a water system over time, their dissolution behavior was studied at various
      degas factors and at two percentages of PEG-40S. It was found that the favored
      shell collapse/shedding mechanism switched, as the dissolution rate increased
      (degas factor decreased), from folding with a smooth surface contour to buckling
      accompanied by surface folding/expulsion with a cyclic buckled-smooth surface
      contour. The compositional change that we made played a more minor role, mainly
      controlling the resistance to mass transfer of the microbubble shell and again
      modifying the mechanism-determinant dissolution rate. The shell resistance
      behavior for these microbubbles varied from that of previous lipid/PEG-40S-coated
      microbubbles by the presence of a maximum in shell resistance during dissolution.
      We hypothesize that the dominance of one collapse mechanism over another for
      these compositions is related to the time scales of two competing processes, fold
      nucleation and area compression. For these mixtures at room temperature, we
      estimate that the maximum area compression rate for folding as the major collapse
      mechanism is approximately 0.2 s (-1), a rate unattainable in a traditional
      Langmuir trough but achievable by the use of a dissolving microbubble.

PMID- 18717574
TI  - Kinetic analysis of interaction of BRCA1 tandem breast cancer c-terminal domains
      with phosphorylated peptides reveals two binding conformations.
AB  - Tandem breast cancer C-terminal (BRCT) domains, present in many DNA repair and
      cell cycle checkpoint signaling proteins, are phosphoprotein binding modules. The
      best-characterized tandem BRCT domains to date are from the protein BRCA1 (BRCA1
      BRCT), an E3 ubiquitin ligase that has been linked to breast and ovarian cancer.
      While X-ray crystallography and NMR spectroscopy studies have uncovered the
      structural determinants of specificity of BRCA1-BRCT for phosphorylated peptides,
      a detailed kinetic and thermodynamic characterization of the interaction is also
      required to understand how structure and dynamics are connected and therefore
      better probe the mechanism of phosphopeptide recognition by BRCT domains. Through
      a global analysis of binding kinetics data obtained from surface plasmon
      resonance (SPR) and stopped-flow fluorescence spectroscopy, we show that the
      recognition mechanism is complex and best modeled by two equilibrium
      conformations of BRCA1-BRCT in the free state that both interact with a
      phosphopeptide, with dissociation constants ( K d) in the micromolar range. We
      show that the apparent global dissociation constant derived from this kinetic
      analysis is similar to the K d values measured using steady-state SPR, isothermal
      titration calorimetry, and fluorescence anisotropy. The dynamic nature of BRCA1
      BRCT may facilitate the binding of BRCA1 to different phosphorylated protein
      targets.

PMID- 18717576
TI  - Silver mirror reaction as an approach to construct superhydrophobic surfaces with
      high reflectivity.
AB  - Superhydrophobic surfaces with high reflectivity might provide a promising self
      cleaning approach in a wide variety of optical applications ranging from traffic
      to solar energy industries. However, the contradiction between the hierarchical
      micronanostructure and the high reflectivity is a challenge for superhydrophobic
      materials with high reflectivity. Here we report a facile method to fabricate a
      superhydrophobic silver film with reflectivity as high as that of polished
      silicon by carefully controlling the seed-induced silver mirror reaction.

PMID- 18717577
TI  - Modulation of drug transport properties by multicomponent diffusion in surfactant
      aqueous solutions.
AB  - Diffusion coefficients of drug compounds are crucial parameters used for modeling
      transport processes. Interestingly, diffusion of a solute can be generated not
      only by its own concentration gradient but also by concentration gradients of
      other solutes. This phenomenon is known as multicomponent diffusion. A
      multicomponent diffusion study on drug-surfactant-water ternary mixtures is
      reported here. Specifically, high-precision Rayleigh interferometry was used to
      determine multicomponent diffusion coefficients for the hydrocortisone-tyloxapol
      water system at 25 degrees C. For comparison, diffusion measurements by dynamic
      light scattering were also performed. In addition, drug solubility was measured
      as a function of tyloxapol concentration, and drug-surfactant thermodynamic
      interactions using the two-phase partitioning model were characterized. The
      diffusion results are in agreement with a proposed coupled multicomponent
      diffusion model for ternary mixtures relevant to nonionic drug and surfactant
      molecules. Theoretical examination of diffusion-based drug transport in the
      presence of concentration gradients of micelles shows that drug fluxes and drug
      concentration profiles are significantly affected by coupled multicomponent
      diffusion. This work provides guidance for the development of accurate models of
      diffusion-based controlled release in multicomponent systems and for the
      applications of micelle concentration gradients to the modulation of diffusion
      based drug transport.

PMID- 18717578
TI  - Ternary inverse opal system for convenient and reversible photonic bandgap
      tuning.
AB  - A ternary system, consisting of air, an air-core/dense-silica-shell core-shell
      particle, and liquids has been used to fabricate an inverse opal structure with
      low fill factor, high refractive index contrast, and reversible tuning
      capabilities of the bandgap spectral position. The original close-packed opal
      structure is a ternary self-assembled photonic crystal from monodisperse and
      spherical polystyrene-core/silica-shell colloidal particles with air as the void
      material. Calcination removed the polystyrene and converted the core-shell
      particles to hollow spheres with a dense shell. In a final step, liquid is
      infiltrated only in the voids between the hollow spheres, but does not penetrate
      in the shell. This allows facile and reversible tuning of the bandgap properties
      in an inverse opal structure.

PMID- 18717579
TI  - Ideal spread monolayer and multilayer formation of fully hydrophobic
      polythiophenes via liquid crystal hybridization on water.
AB  - The spread monolayer formation of hydrophobic poly(3-alkylthiophene)s (P3ATs),
      regioregular poly(3-hexylthiophene) ( HT-P3HT), regioregular poly(3
      dodecylthiophene) ( HT-P3DT), and regioirregular poly(3-hexylthiophene) ( RI
      P3HT), were attained on the water surface via cospreading with a liquid-crystal
      molecule, 4'-pentyl-4-cyanobiphenyl (5CB). The spread monolayers were
      characterized by pi- A isotherms, Brewster angle microscopy (BAM), and atomic
      force microscopy (AFM). The molecular area for the cospread mixtures of P3ATs and
      5CB expanded more than that of pure P3ATs as shown from the pi-A isotherms. BAM
      revealed that the mixed film forms the monomolecularly uniform and flat films on
      water. AFM elucidated that the spread monolayer of the hydrophobic P3ATs formed
      on the top of the 5CB monolayer on water with thicknesses of ca. 1.6 and ca. 2.6
      nm for the two P3HTs and HT-P3DT, respectively. The P3AT/5CB hybrid monolayers
      could be fully transferred onto a solid substrate, and pure P3AT monolayers were
      obtained after volatilization of 5CB by gentle heating. The multilayer formation
      of pure P3AT monolayers was prepared by layer-by-layer deposition involving
      repeating horizontal deposition and successive volatilization of 5CB. Grazing
      angle incidence X-ray diffraction measurements showed that the lamella plane of
      the P3ATs is perfectly oriented parallel to the substrate plane in the resulting
      thin films. This shows a marked contrast with those obtained by spin casting
      using the identical polymer, where both in-plane and out-of-plane lamellae are
      involved. These thin films with perfectly controlled lamella orientation should
      be of great significance as the model system for evaluating the charge mobility
      for organic polymer electric devices.

PMID- 18717580
TI  - Growth of tetrahedral silver nanocrystals in aqueous solution and their SERS
      enhancement.
AB  - Silver nanocrystals with tetrahedral shapes and {111} faces have been synthesized
      by the light-driven growth method in an aqueous solution. The nanocrystals of
      T(d) symmetry were formed under the effect of tartrate and citrate as the
      structural-directing reagents at the appropriate stages of reaction. Further, the
      nanocrystals may be assembled through electrostatic interaction to develop large
      scale particle surfaces with sharp vertexes, which can generate strong localized
      electromagnetic field for surface-enhanced Raman scattering (SERS) studies.
      Benzenethiol was used as the probe to evaluate their SERS enhancement, and
      enhancement factors of up to 10(6) are reached. As a kind of promising material,
      these novel nanocrystals will be applied in surface enhanced spectroscopy and
      plasmonics field.

PMID- 18717581
TI  - Design, synthesis, and evaluation of novel organophosphorus inhibitors of
      bacterial ureases.
AB  - A new group of organophosphorus inhibitors of urease, P-methyl phosphinic acids
      was discovered by using the structure based inhibitor design approach. Several
      derivatives of the lead compound, aminomethyl(P-methyl)phosphinic acid, were
      synthesized successfully. Their potency was evaluated in vitro against urease
      from Bacillus pasteurii and Proteus vulgaris. The studied compounds constitute a
      group of competitive, reversible inhibitors of bacterial ureases. Obtained
      thiophosphinic analogues of the most effective structures exhibited kinetic
      characteristics of potent, slow binding urease inhibitors, with Ki = 170 nM
      (against B. pasteurii enzyme) for the most active N-( N'
      benzyloxycarbonylglycyl)aminomethyl(P-methyl)phosphinothioic acid.

PMID- 18717582
TI  - Predicting kinase selectivity profiles using Free-Wilson QSAR analysis.
AB  - Kinases are involved in a variety of diseases such as cancer, diabetes, and
      arthritis. In recent years, many kinase small molecule inhibitors have been
      developed as potential disease treatments. Despite the recent advances,
      selectivity remains one of the most challenging aspects in kinase inhibitor
      design. To interrogate kinase selectivity, a panel of 45 kinase assays has been
      developed in-house at Pfizer. Here we present an application of in silico
      quantitative structure activity relationship (QSAR) models to extract rules from
      this experimental screening data and make reliable selectivity profile
      predictions for all compounds enumerated from virtual libraries. We also propose
      the construction of R-group selectivity profiles by deriving their activity
      contribution against each kinase using QSAR models. Such selectivity profiles can
      be used to provide better understanding of subtle structure selectivity
      relationships during kinase inhibitor design.

PMID- 18717583
TI  - Hetero-bimetallic complexes involving vanadium(V) and rhenium(VII) centers,
      connected by unsupported mu-oxido bridge: synthesis, characterization, and redox
      study.
AB  - Heterobimetallic complexes of a vanadium(V) and rhenium(VII) combination
      connected by a mu-oxido bridge [LVO(mu-O)ReO 3].H 2O [H 2L = N, N'-ethylene
      bis(salicylideneimine) (H 2salen) and its methoxy derivative] ( 1, 2) are
      reported. The compounds have been prepared by a single-pot synthesis in which the
      precursor [V (IV)OL] complexes are allowed to be oxidized aerially in the
      presence of added perrhenate. The oxidized [V (V)OL] (+) species accommodate the
      ReO 4 (-) anion in their vacant coordination site, trans to the terminal oxido
      group, providing the complexes 1 and 2. The later generates a binuclear
      oxovanadium(V) compound [H 2en][(TBC)VO(mu-TBC) 2OV(TBC)].5H 2O ( 3) when treated
      with tetrabromocatechol. Single crystal X-ray diffraction analysis and (1)H NMR
      spectroscopy have been used to establish their identities. In compound 2, the
      Re(1)-O(11)-V(1) bridge angle is barely linear [170.2(3) degrees ] with a Re...V
      separation of 3.9647(9) A. The redox behavior of 1 and 2 are quite interesting,
      each undergoing two reductions both in the positive potential range at E 1/2 =
      0.59 (process I) and E 1/2 = 0.16 V (process II) versus Ag/AgCl reference
      (corresponding potentials are 0.59 and 0.18 V for 2). Process I has a single
      electron stoichiometry involving the [VO(salen)] part of the complexes as
      established by combined coulometry-Electron Paramagnetic Resonance (EPR)
      experiments which provide an eight-line isotropic EPR pattern at room temperature
      (<g> = 1.967; <A> = 87 x 10 (-4) cm (-1)), characteristic of an unpaired electron
      being coupled to a vanadium nuclear spin ( (51)V, I = 7/2). The almost linear V-O
      Re bridge in 1 and 2 allows this unpaired electron to interact effectively with
      the neighboring Re nuclear spin, leading to familiar " two-line pattern"
      superhyperfine coupling ( A ( (185,187)Re) = 20.7 x 10 (-4) cm (-1)). Process II,
      on the other hand, is based on a Re(VII/VI) electron transfer as confirmed by
      differential pulse and normal pulse voltammetric experiments.

PMID- 18717584
TI  - Near-infrared luminescence of nine-coordinate neodymium complexes with
      benzimidazole-substituted 8-hydroxyquinolines.
AB  - A new class of benzimidazole-substituted 8-hydroxyquinoline ligands has been
      prepared that contain a monoanionic tridentate N,N,O-coordinating unit. These
      ligands form charge-neutral lanthanide complexes of the type [Ln(L-R) 3]. nH 2O
      or [Ln 2(L2) 3]. nH 2O ( n = 1-3) with early lanthanides from La (III) to Gd
      (III) inclusive. Crystallographic characterization was carried out for 11
      complexes with 6 different ligands. In all of these structures, the lanthanide
      ion was found to be nine-coordinated by three ligands arranged in an "up-up-down"
      fashion around the metal center. The coordination environment can be described as
      a tricapped trigonal prism, with N atoms of quinoline rings occupying capping
      positions. Upon deprotonation of the ligand and complex formation, a new
      absorption band appears in the visible range of the spectrum with a maximum in
      the range of 466-483 nm and molar absorption coefficient of (7.2 - 18) x 10 (3) M
      (-1) cm (-1). Its origin is likely to be an intraligand phenolate-to-pyridyl
      charge transfer transition centered on the 8-hydroxyquinolate chromophore. Upon
      excitation in ligand absorption bands, new Nd (III) complexes display
      characteristic metal-centered luminescence in the near-infrared region from 850
      to 1450 nm with quantum yields and lifetimes in solid state at room temperature
      as high as 0.34% and 1.2 mus, respectively.

PMID- 18717585
TI  - Biomimetic synthesis and structural revision of (+/-)-tridachiahydropyrone.
AB  - A short synthesis of the revised structure of the marine natural product
      tridachiahydropyrone is described. A novel biomimetic photochemical
      electrocyclization was employed to construct the bicyclic carbon framework from
      an open-chain polyene precursor. The spectroscopic data matched that of the
      isolated natural product, supporting a revised structure of this complex
      metabolite.

PMID- 18717586
TI  - Antiurolithic effect of lupeol and lupeol linoleate in experimental
      hyperoxaluria.
AB  - The present study was undertaken to explore the efficiency of the pentacyclic
      triterpene lupeol (1) and its ester derivative, lupeol linoleate (2), in
      experimental hyperoxaluria. Hyperoxaluria was induced in male Wistar rats with
      0.75% ethylene glycol (EG) in drinking water for 28 days. Hyperoxaluric animals
      were supplemented orally with 1 and 2 (50 mg/kg body wt/day) throughout the
      experimental period of 28 days. The renal enzymes were assayed as markers of
      renal tissue integrity. The redox status and oxalate metabolism in animals under
      oxalate overloading was also assessed. Microscopic analysis was done to
      investigate the abnormalities associated with oxalate exposure in renal tissues.
      Increase in oxidative milieu in hyperoxaluria was evident by increased lipid
      peroxidation (LPO) and decreased enzymic and nonenzymic antioxidants. Decrease in
      the activities of renal enzymes exemplified the damage induced by oxalate, which
      correlated positively with increased LPO and increased oxalate synthesis. Renal
      microscopic analysis further emphasized the oxalate-induced damage. These
      abnormal biochemical and histological aberrations were attenuated with test
      compound treatment, with 2 more effective than 1. From the present study, it can
      be concluded that 1 and 2 may serve as candidates for alleviating oxalate
      toxicity.

PMID- 18717587
TI  - Straightforward synthesis of thiodisaccharides by ring-opening of sugar epoxides.
AB  - 3,4-Anhydro hexopyranosides have been prepared by diastereoselective epoxidation
      of derivatives of 2-propyl 3,4-dideoxy-alpha-D-erythro-hex-3-enopyranoside (5),
      selectively protected at HO-2 and HO-6. The allylic group at C-2, in 5 and
      derivatives, plays a critical role in the facial selectivity of the epoxidation
      reaction. Thus, the free HO-2 in 3 (the 6-O-acetyl derivative of 5) directs the
      attack of m-chloroperbenzoic acid from the more hindered alpha face of the
      molecule to give 2-propyl 6-O-acetyl-3,4-anhydro-alpha-D-allopyranoside (7)
      accompanied by the beta epoxide 6 as a very minor product. Reverse
      diastereoselectivity has been obtained when the HO-2 in 3 was substituted by a
      bulky tert-butyldimethylsilyl (TBS) group. In this case, the major isomer was the
      2-O-TBS derivative of 6 (alpha-D-galacto configuration). The ring-opening of
      sugar epoxides by nucleophilic per-O-acetyl-1-thio-beta-D-glucopyranose (11) was
      employed as a convenient approach to the synthesis of (1-->3)- and (1-->4)
      thiodisaccharides. For example, ring-opening of the oxirane 7 by 11 led to the
      expected regioisomeric per-O-acetyl thiodisaccharides beta-D-Glc-S-(1-->3)-4-thio
      alpha-D-Glc-O-iPr (12) and beta-D-Glc-S-(1-->4)-4-thio-alpha-D-Gul-O-iPr (13).
      Regioselectivity in the construction of the (1-->4)-thioglycosidic linkage could
      be achieved by hindering C-3 of the 3,4-anhydro sugar with a bulky silyloxy group
      at the vicinal C-2. For instance, coupling of the 2-O-TBS derivative of 7 with 11
      led regioselectively to the protected thiodisaccharide beta-D-Glc-S-(1-->4)-4
      thio-alpha-D-Glc-O-iPr (27). The utility of the approach was demonstrated through
      the synthesis of sulfur-linked analogues of naturally occurring (laminarabiose
      and cellobiose) and non-natural disaccharides (i.e., beta-D-Glc-(1-->4)-alpha-D
      Gul).

PMID- 18717588
TI  - Screening of photocatalysts by scanning electrochemical microscopy.
AB  - A method for rapid screening of photocatalysts employing a form of scanning
      electrochemical microscopy (SECM) is described. A piezoelectric dispenser was
      used to deposit arrays composed of approximately 300-microm-size photocatalyst
      spots with different compositions onto conducting glass, fluorine-doped tin oxide
      substrate. The scanning tip of the SECM was replaced by a fiber optic connected
      to a xenon lamp and was rapidly scanned over the array. In this arrangement, the
      photocatalytic performance of the spots was evaluated by measuring the
      photocurrent at the substrate of the array. A fiber optic with a ring electrode
      can also be used to electrochemically detect products of the photoreaction.
      Several iron oxide-based bimetallic oxide combinations were found to exhibit
      enhanced photocatalytic activity, when compared to pure alpha-Fe2O3. These
      combinations included iron-palladium, iron-europium, and iron-rubidium in
      specific ratios. A trimetallic bismuth-vanadium-zinc oxide combination was also
      found to show a higher photocurrent, by approximately 40%, compared to BiVO3.

PMID- 18717589
TI  - Mismatched and matched dNTP incorporation by DNA polymerase beta proceed via
      analogous kinetic pathways.
AB  - While matched nucleotide incorporation by DNA polymerase beta (Pol beta) has been
      well-studied, a true understanding of polymerase fidelity requires comparison of
      both matched and mismatched dNTP incorporation pathways. Here we examine the
      mechanism of misincorporation for wild-type (WT) Pol beta and an error-prone
      I260Q variant using stopped-flow fluorescence assays and steady-state
      fluorescence spectroscopy. In stopped-flow, a biphasic fluorescence trace is
      observed for both enzymes during mismatched dNTP incorporation. The fluorescence
      transitions are in the same direction as that observed for matched dNTP, albeit
      with lower amplitude. Assignments of the fast and slow fluorescence phases are
      designated to the same mechanistic steps previously determined for matched dNTP
      incorporation. For both WT and I260Q mismatched dNTP incorporation, the rate of
      the fast phase, reflecting subdomain closing, is comparable to that induced by
      correct dNTP. Pre-steady-state kinetic evaluation reveals that both enzymes
      display similar correct dNTP insertion profiles, and the lower fidelity intrinsic
      to the I260Q mutant results from enhanced efficiency of mismatched incorporation.
      Notably, in comparison to WT, I260Q demonstrates enhanced intensity of
      fluorescence emission upon mismatched ternary complex formation. Both kinetic and
      steady-state fluorescence data suggest that relaxed discrimination against
      incorrect dNTP by I260Q is a consequence of a loss in ability to destabilize the
      mismatched ternary complex. Overall, our results provide first direct evidence
      that mismatched and matched dNTP incorporations proceed via analogous kinetic
      pathways, and support our standing hypothesis that the fidelity of Pol beta
      originates from destabilization of the mismatched closed ternary complex and
      chemical transition state.

PMID- 18717590
TI  - EPR and Mossbauer spectroscopy of intact mitochondria isolated from Yah1p
      depleted Saccharomyces cerevisiae.
AB  - Yah1p, an [Fe 2S 2]-containing ferredoxin located in the matrix of Saccharomyces
      cerevisiae mitochondria, functions in the synthesis of Fe/S clusters and heme a
      prosthetic groups. EPR, Mossbauer spectroscopy, and electron microscopy were used
      to characterize the Fe that accumulates in Yah1p-depleted isolated intact
      mitochondria. Gal- YAH1 cells were grown in standard rich media (YPD and YPGal)
      under O 2 or argon atmospheres. Mitochondria were isolated anaerobically, then
      prepared in the as-isolated redox state, the dithionite-treated state, and the O
      2-treated state. The absence of strong EPR signals from Fe/S clusters when Yah1p
      was depleted confirms that Yah1p is required in Fe/S cluster assembly. Yah1p
      depleted mitochondria, grown with O 2 bubbling through the media, accumulated
      excess Fe (up to 10 mM) that was present as 2-4 nm diameter ferric nanoparticles,
      similar to those observed in mitochondria from yfh1Delta cells. These particles
      yielded a broad isotropic EPR signal centered around g = 2, characteristic of
      superparamagnetic relaxation. Treatment with dithionite caused Fe (3+) ions of
      the nanoparticles to become reduced and largely exported from the mitochondria.
      Fe did not accumulate in mitochondria isolated from cells grown under Ar; a
      significant portion of the Fe in these organelles was in the high-spin Fe (2+)
      state. This suggests that the O 2 used during growth of Gal- YAH1 cells is
      responsible, either directly or indirectly, for Fe accumulation and for oxidizing
      Fe (2+) --> Fe (3+) prior to aggregation. Models are proposed in which the
      accumulation of ferric nanoparticles is caused either by the absence of a ligand
      that prevents such precipitation in wild-type mitochondria or by a more oxidizing
      environment within the mitochondria of Yah1p-depleted cells exposed to O 2. The
      efficacy of reducing accumulated Fe along with chelating it should be considered
      as a strategy for its removal in diseases involving such accumulations.

PMID- 18717591
TI  - Importance of the domain-domain interface to the catalytic action of the NO
      synthase reductase domain.
AB  - Calmodulin (CaM) activates NO synthase (NOS) by binding to a 20 amino acid
      interdomain hinge in the presence of Ca (2+), inducing electrons to be
      transferred from the FAD to the heme of the enzyme via a mobile FMN domain. The
      activation process is influenced by a number of structural features, including an
      autoinhibitory loop, the C-terminal tail of the enzyme, and a number of
      phosphorylation sites. Crystallographic and other recent experimental data imply
      that the regulatory elements lie within the interface between the FAD- and FMN
      binding domains, restricting the movement of the two cofactors with respect to
      each other. Arg1229 of rat neuronal NOS is a conserved residue in the FAD domain
      that forms one of only two electrostatic contacts between the domains. Mutation
      of this residue to Glu reverses its charge and is expected to induce an
      interdomain repulsion, allowing the importance of the interface and domain-domain
      motion to be probed. The charge-reversal mutation R1229E has three dramatic
      effects on catalysis: (i) hydride transfer from NADPH to FAD is activated in the
      CaM-free enzyme, (ii) FAD to FMN electron transfer is inhibited in both forms,
      and (iii) electron transfer from FMN to the surrogate acceptor cytochrome c is
      activated in the CaM-free enzyme. As a result, during steady-state turnover with
      cytochrome c, calmodulin now deactivates the enzyme and causes cytochrome c
      dependent inhibition. Evidently, domain-domain separation is large enough in the
      mutant to accommodate another protein between the cofactors. The effects of this
      single charge reversal on three distinct catalytic events illustrate how each is
      differentially dependent on the enzyme conformation and support a model for
      catalytic motion in which steps i, ii, and iii occur in the hinged open, closed,
      and open states, respectively. This model is also likely to apply to related
      enzymes such as cytochrome P450 reductase.

PMID- 18717592
TI  - Assembly and disassembly of the photosystem II manganese cluster reversibly
      alters the coupling of the reaction center with the light-harvesting
      phycobilisome.
AB  - The light-driven oxidative assembly of Mn (2+) ions into the H 2O oxidation
      complex (WOC) of the photosystem II (PSII) reaction center is termed
      photoactivation. The fluorescence yield characteristics of Synechocystis sp.
      PCC6803 cells undergoing photoactivation showed that basal fluorescence, F 0,
      exhibited a characteristic decline when red, but not blue, measuring light was
      employed. This result was traced to a progressive increase in the coupling of the
      phycobilisome (PBS) to the PSII reaction center as determined by observing the
      changes in room temperature and 77 K fluorescence emission spectra that accompany
      photoactivation. The results support the hypothesis that strong energetic
      coupling of the PBS to the PSII reaction center depends upon the formation of an
      active WOC, which presumably diminishes the likelihood of photodamage to reaction
      centers that have either lost an intact Mn cluster or are in the process of
      assembling an active WOC.

PMID- 18717593
TI  - Thioredoxin reductase from Thermoplasma acidophilum: a new twist on redox
      regulation.
AB  - Thioredoxin reductases (TrxRs) regulate the intracellular redox environment by
      using NADPH to provide reducing equivalents for thioredoxins (Trxs). Here we
      present the cloning and biochemical characterization of a putative TrxR (Ta0984)
      and a putative Trx (Ta0866) from Thermoplasma acidophilum. Our data identify
      Ta0866 as a Trx through its capacity to reduce insulin and be reduced by
      Escherichia coli TrxR in a NADPH-dependent manner. Our data also establish Ta0984
      as a TrxR due to its ability to reduce T. acidophilum Trx ( taTrx), although not
      in a NADPH- or NADH-dependent manner. To explore the apparent inability of taTrxR
      to use NADPH or NADH as a reductant, we carried out a complete electrochemical
      characterization, which suggests that redox potential is not the source of this
      nonreactivity [Hamill et al. (2008) Biochemistry 47, 9738-9746]. Turning to
      crystallographic analysis, a 2.35 A resolution structure of taTrxR, also
      presented here, shows that despite the overall structural similarity to the well
      characterized TrxR from E. coli (RMSD 1.30 A (2) for chain A), the "NADPH binding
      pocket" is not conserved. E. coli TrxR residues implicated in NADPH binding,
      H175, R176, R177, and R181, have been substituted with E185, Y186, M187, and M191
      in the ta protein. Thus, we have identified a Trx and TrxR protein system from T.
      acidophilum for which the TrxR shares overall structural and redox properties
      with other TrxRs but lacks the appropriate binding motif to use the standard
      NADPH reductant. Our discovery of a TrxR that does not use NADPH provides a new
      twist in redox regulation.

PMID- 18717594
TI  - Direct electrochemical analyses of a thermophilic thioredoxin reductase:
      interplay between conformational change and redox chemistry.
AB  - Thioredoxin reductases (TrxRs) are flavin-containing dithioloxidoreductases that
      couple reduction equivalents from the soluble NAD(P)H pool to the soluble protein
      thioredoxin (Trx). Previous crystallographic studies of the Escherichia coli
      enzyme ( ecTrxR) have shown that low molecular weight TrxRs can adopt two
      distinct conformations: the first (FO) is required for the oxidation of the
      flavin cofactor and the generation of reduced Trx; the second (FR) is adopted for
      the reduction of the flavin by NAD(P)H. Here, protein electrochemistry has been
      used to interrogate the equilibrium between the oxidized and reduced
      conformations of the ecTrxR and a novel, low molecular weight TrxR from the
      thermophilic archaeon Thermoplasma acidophilum ( taTrxR) that is characterized
      structurally and biochemically in the accompanying paper [Hernandez et al. (2008)
      Biochemistry 47, 9728-9737]. A reversible electrochemical response is observed
      that reveals a dynamic behavior dependent upon the temperature of the experiment.
      At low temperatures (283 K) a broad, quasi-reversible electrochemical envelope is
      observed centered at a value of approximately -300 mV and displaying a peak width
      of over 150 mV. The voltammetric response sharpens dramatically as the
      temperature increases, becoming much more reversible (as determined by peak
      separation and peak width). The overall potential and shape of the voltammetric
      data indicate that the flavin (FAD/FADH 2) and disulfide/dithiol couples are very
      close in thermodynamic potentials, and the data are interpreted in terms of the
      model of two-state conformational change between flavin reducing (FR) and flavin
      oxidizing (FO) states, where the difference in potential for the flavin and
      disulfide cofactors must be within 40 mV of one another. In this model, the low
      temperature peak broadening is interpreted as an indication of a heterogeneous
      population of TrxR conformations that exist at low temperature; at higher
      temperatures, FO and FR conformers can rapidly interconvert, and voltammetry
      reports upon an average potential of the conformations.

PMID- 18717595
TI  - Single mutations change CYP2F3 from a dehydrogenase of 3-methylindole to an
      oxygenase.
AB  - Pulmonary cytochrome P450 2F3 (CYP2F3) catalyzes the dehydrogenation of the
      pneumotoxin 3-methylindole (3MI) to an electrophilic intermediate, 3
      methyleneindolenine, which is responsible for the toxicity of the parent
      compound. Members of the CYP2F subfamily are the only enzymes known to
      exclusively dehydrogenate 3MI, without detectable formation of oxygenation
      products. Thus, CYP2F3 is an attractive model to study dehydrogenation
      mechanisms. The purpose of this study was to identify specific residues that
      could facilitate 3MI dehydrogenation. Both single and double mutations were
      constructed to study the molecular mechanisms that direct dehydrogenation. Double
      mutations in substrate recognition sites (SRS) 1 produced an inactive enzyme,
      while double mutants in SRS 4 did not alter 3MI metabolism. However, double
      mutations in SRS 5 and SRS 6 successfully introduced oxygenase activity to
      CYP2F3. Single mutations in SRS 5, SRS 6 and near SRS 2 also introduced 3MI
      oxygenase activity. Mutants S474H and D361T oxygenated 3MI but also increased
      dehydrogenation rates, while G214L, E215Q and S475I catalyzed 3MI oxygenation
      exclusively. A homology model of CYP2F3 was precisely consistent with specific
      dehydrogenation of 3MI via initial hydrogen atom abstraction from the methyl
      group. In addition, intramolecular kinetic deuterium isotope studies demonstrated
      an isotope effect ( K H/ K D) of 6.8. This relatively high intramolecular
      deuterium isotope effect confirmed the initial hydrogen abstraction step; a
      mutant (D361T) that retained the dehydrogenation reaction exhibited the same
      deuterium isotope effect. The results showed that a single alteration, such as a
      serine to isoleucine change at residue 475, dramatically switched catalytic
      preference from dehydrogenation to oxygenation.

PMID- 18717596
TI  - Insight into the coupling mechanism of the vitamin K-dependent carboxylase:
      mutation of histidine 160 disrupts glutamic acid carbanion formation and
      efficient coupling of vitamin K epoxidation to glutamic acid carboxylation.
AB  - Vitamin K-dependent (VKD) proteins become activated by the VKD carboxylase, which
      converts Glu's to carboxylated Glu's (Gla's) in their Gla domains. The
      carboxylase uses vitamin K epoxidation to drive Glu carboxylation, and the two
      half-reactions are coupled in 1:1 stoichiometry by an unknown mechanism. We now
      report the first identification of a residue, His160, required for coupling. A
      H160A mutant showed wild-type levels of epoxidation but substantially less
      carboxylation. Monitoring proton abstraction using a peptide with Glu tritiated
      at the gamma-carbon position revealed that poor coupling was due to impaired
      carbanion formation. H160A showed a 10-fold lower ratio of tritium release to
      vitamin K epoxidation than wild-type enzyme (i.e., 0.12 versus 1.14,
      respectively), which could fully account for the fold decrease in coupling
      efficiency. The Ala substitution in His160 did not affect the K m for vitamin K
      and caused only a 2-fold increase in the K m for Glu and 2-fold decrease in the
      activation of vitamin K epoxidation by Glu. The H160A K m for CO 2 was 5-fold
      higher than the wild-type enzyme. However, the k cat for H160A carboxylation was
      8-9-fold lower than the wild-type enzyme with all three substrates (i.e., Glu, CO
      2, and vitamin K), suggesting a catalytic role for His160 in carbanion formation.
      We propose that His160 facilitates the formation of the transition state for
      carbanion formation. His160 is highly conserved in metazoan VKD carboxylases but
      not in some bacterial orthologues (acquired by horizontal gene transfer), which
      has implications for how bacteria have adapted the carboxylase for novel
      functions.

PMID- 18717597
TI  - Incorporation of hydrostatic pressure into models of hydrogen tunneling
      highlights a role for pressure-modulated promoting vibrations.
AB  - Hydrostatic pressure offers an alternative to temperature as an experimental
      probe of hydrogen-transfer reactions. H tunneling reactions have been shown to
      exhibit kinetic isotope effects (KIEs) that are sensitive to pressure, and
      environmentally coupled H tunneling reactions, those reactions in which H
      transfer is coupled to atomic fluctuations (a promoting vibration) along the
      reaction coordinate, often have quite temperature-dependent KIEs. We present here
      a theoretical treatment of the combined effect of temperature and pressure on
      environmentally coupled H tunneling reactions. We develop a generalized
      expression for the KIE, which can be used as a simple fitting function for
      combined experimental temperature- and pressure-dependent KIE data sets. With
      this expression, we are able to extract information about the pressure dependence
      of both the apparent tunneling distance and the frequency of the promoting
      vibration. The KIE expression is tested on two data sets {the reduction of
      chloranil by leuco crystal violet [Isaacs, N. S., Javaid, K., and Rannala, E.
      (1998) J. Chem. Soc., Perkin Trans. 2, 709-711] and the reduction of morphinone
      reductase by NADH [Hay, S., Sutcliffe, M. J., and Scrutton, N. S. (2007) Proc.
      Natl. Acad. Sci. U.S.A. 104, 507-512]} and suggests that hydrostatic pressure is
      a sensitive probe of nuclear quantum mechanical effects in H-transfer reactions.

PMID- 18717598
TI  - Interaction of a cyclic, bivalent smac mimetic with the x-linked inhibitor of
      apoptosis protein.
AB  - We have designed and synthesized a cyclic, bivalent Smac mimetic (compound 3) and
      characterized its interaction with the X-linked inhibitor of apoptosis protein
      (XIAP). Compound 3 binds to XIAP containing both BIR2 and BIR3 domains with a
      biphasic dose-response curve representing two binding sites with IC 50 values of
      0.5 and 406 nM, respectively. Compound 3 binds to XIAPs containing the BIR3-only
      and BIR2-only domain with K i values of 4 nM and 4.4 microM, respectively. Gel
      filtration experiments using wild-type and mutated XIAPs showed that 3 forms a
      1:2 stoichiometric complex with XIAP containing the BIR3-only domain. However, it
      forms a 1:1 stoichiometric complex with XIAP containing both BIR2 and BIR3
      domains, and both BIR domains are involved in the binding. Compound 3 efficiently
      antagonizes inhibition of XIAP in a cell-free functional assay and is >200 times
      more potent than its corresponding monovalent compound 2. Determination of the
      crystal structure of 3 in complex with the XIAP BIR3 domain confirms that 3
      induces homodimerization of the XIAP BIR3 domain and provides a structural basis
      for the cooperative binding of one molecule of compound 3 to two XIAP BIR3
      molecules. On the basis of this crystal structure, a binding model of XIAP
      containing both BIR2 and BIR3 domains and 3 was constructed, which sheds light on
      the ability of 3 to relieve the inhibition of XIAP with not only caspase-9 but
      also caspase-3/-7. Compound 3 is cell-permeable, effectively activates caspases
      in whole cells, and potently inhibits cancer cell growth. Compound 3 is a useful
      biochemical and pharmacological tool for further elucidating the role of XIAP in
      regulation of apoptosis and represents a promising lead compound for the design
      of potent, cell-permeable Smac mimetics for cancer treatment.

PMID- 18717600
TI  - Atom movement on a dislocated surface.
AB  - The standard picture of growth at a screw dislocation assumes that the movement
      of adatoms on a dislocation loop is the same as on an ideal plane. We have
      examined this proposition by investigating the movement of a single tungsten
      adatom on a W(110) plane intersected by a screw dislocation. Surprisingly enough,
      adatom movement was entirely different than on a normal (110) plane: the overall
      diffusivity was higher, and the mobility varied with the location of the adatom
      relative to the dislocation core. This study demonstrates that surface transport
      is strongly affected in the vicinity of dislocations.

PMID- 18717599
TI  - A microscopic study of the deoxyhemoglobin-catalyzed generation of nitric oxide
      from nitrite anion.
AB  - There is recent evidence suggesting that nitrite anion (NO 2 (-)) represents the
      major intravascular NO storage molecule whose transduction to NO is facilitated
      by a reduction mechanism catalyzed by deoxygenated hemoglobin (deoxy-Hb). In this
      work, we provide a detailed microscopic study of deoxy-Hb nitrite reductase (NIR)
      activity by combining classical molecular dynamics and hybrid quantum mechanical
      molecular mechanical simulations. Our results point out that two alternative
      mechanisms could be operative and suggest that the most energetic barriers should
      stem from either reprotonation of the distal histidine or NO dissociation from
      the ferric heme. In the first proposed mechanism, which is similar to that
      proposed for bacterial NIRs, nitrite anion or nitrous acid coordinates to the
      heme through the N atom. This pathway involves HisE7 in a one or two proton
      transfer process, depending on whether the active species is nitrite anion or
      nitrous acid, to yield an intermediate Fe(III)NO species which eventually
      dissociates leading to NO and methemoglobin. In the second mechanism, the nitrite
      anion coordinates to the heme through the O atom. This pathway requires only one
      proton transfer from HisE7 and leads directly to the formation of a hydroxo
      Fe(III) complex and NO.

PMID- 18717601
TI  - Ligand customization and DNA functionalization of gold nanorods via round-trip
      phase transfer ligand exchange.
AB  - Customizable ligand exchange of gold nanorods (NRs) is described. NRs are
      synthesized with the cationic surfactant cetyltrimethylammonium bromide (CTAB)
      which is exchanged with thiolated ligands that enable suspension in buffer.
      Exchange is achieved by a two phase extraction. First, CTAB is removed from the
      NR-CTAB by extracting the NRs into an organic phase via the ligand dodecanethiol
      (DDT). The NR-DDT are then extracted into an aqueous phase by mercaptocarboxylic
      acids (MCA), HS-(CH 2)n -COOH (n = 5, 10, and 15). Ligands can be further
      customized to thiolated poly(ethylene glycol), PEG MW (MW = 356, 5000, and 1000).
      Ligand-exchanged NRs (NR-MCA and NR-PEG(MW)) are stable in buffer, do not
      aggregate, and do not change size upon ligand exchange. They can be run in
      agarose gel electrophoresis with narrow bands, indicating uniform charge
      distribution and enabling quantitative analysis. DNA functionalization of NR-MCA
      is straightforward and quantifiable, with minimal nonspecific adsorption.

PMID- 18717602
TI  - Can we define acne as a chronic disease? If so, how and when?
AB  - There is widespread misunderstanding of acne amongst both the medical and lay
      community, who often perceive the condition to be a simple, self-limited
      affliction of adolescents. Because many think that the disease "will go away on
      its own," they do not feel an urgency to aggressively treat acne. However, very
      often the reality is that acne treatment can be quite difficult. Furthermore,
      acne can be a devastating disease for the patient, since it manifests on visible
      body parts and in children near puberty, who are vulnerable both socially and
      psychologically. Most typically, acne is not an acute disease but rather a
      condition that continuously changes in its distribution and severity. Usually,
      acne treatment is necessary for many months and sometimes years. Despite
      treatment, acne may cause scarring and associated negative psychological effects.
      It is important for both patients and physicians to be aware that very effective
      treatments are available. It is also important to realize that new studies have
      proven the benefit of maintenance therapy with topical retinoids; these agents
      can minimize the potential for relapse, which is part of the natural history of
      acne. This article reviews the evidence suggesting that acne is a chronic disease
      in at least a subset of individuals. The members of the Global Alliance to
      Improve Outcomes in Acne believe that acne should be recognized and investigated
      as a chronic disease. This will change expectations of clinical trial design and
      treatment and will highlight gaps in the knowledge of acne epidemiology. The
      result should be an improvement in patient outcomes.

PMID- 18717603
TI  - EGFR inhibitor-associated acneiform folliculitis: assessment and management.
AB  - Treatment with epidermal growth factor receptor (EGFR) inhibitors is associated
      with cutaneous adverse events, including acneiform folliculitis, dry skin, and
      nail disorders. Acneiform folliculitis is a class effect of EGFR inhibitors that
      is thought to be a direct result of EGFR blockade in the hair follicle. The
      folliculitis is typically mild to moderate in severity and reversible without
      scarring upon treatment completion. Dose modification or treatment
      discontinuation is rarely necessary, except in severe cases. Standard acne
      treatments (e.g. benzoyl peroxide, oral or topical antibacterials, retinoic acid)
      may provide some benefit, based on anecdotal reports. Clinicians should be aware
      of the possibility of superinfection with Staphylococcus aureus, in some cases
      involving meticillin-resistant strains, which may require treatment with oral
      antibacterials. Further study is needed to determine how the presence and
      severity of acneiform folliculitis are related to clinical outcomes, and which
      patients taking EGFR inhibitors are more likely to develop this disorder.

PMID- 18717604
TI  - Mucocutaneous manifestations of Epstein-Barr virus infection.
AB  - This review focuses on Epstein-Barr virus (EBV) infection, diagnosis, and current
      treatment, with emphasis on EBV-associated mucocutaneous manifestations in
      primary infections, acute EBV-associated syndromes, chronic infections,
      lymphoproliferative disorders, and lymphomas. In primary infection, EBV infects B
      cells and can cause mucocutaneous manifestations in infectious mononucleosis or
      acute EBV-associated syndromes such as Gianotti-Crosti syndrome and
      hemophagocytic syndrome. EBV then persists in the majority of humans generally
      without causing disease. In some cases, however, latent EBV infection may result
      in diseases such as hydroa vacciniforme, hypersensitivity to mosquito bites, and
      lymphoproliferative disorders such as plasmablastic lymphoma, oral hairy
      leukoplakia, and post-transplant lymphoproliferative disorders, particularly in
      immunocompromised patients. Latent EBV infection has also been implicated in a
      variety of malignant conditions such as Burkitt lymphoma, Hodgkin lymphoma,
      nasopharyngeal carcinoma, and Kikuchi histocytic necrotizing lymphadenitis. Since
      the immune system is critical in preventing the progression of EBV disease, the
      immunologic status of the patient plays a crucial role in the subsequent
      development of pathologies.

PMID- 18717605
TI  - Tumor immunotherapy in melanoma: strategies for overcoming mechanisms of
      resistance and escape.
AB  - The incidence of melanoma has been steadily increasing over the last 3 decades.
      Currently, there are several approved treatments for metastatic melanoma,
      including chemotherapy and biologic therapy as both single treatments and in
      combination, but none is associated with a significant increase in survival. The
      chemotherapeutic agent dacarbazine is the standard treatment for metastatic
      melanoma, with a response rate of 15-20%, although most responses are not
      sustained. One of the main problems with melanoma treatment is chemotherapeutic
      resistance. The mechanisms of resistance of melanoma cells to chemotherapy have
      yet to be elucidated. Following treatment with dacarbazine, melanoma cells
      activate the extracellular signal-regulated kinase pathway, which results in over
      expression and secretion of interleukin (IL)-8 and vascular endothelial growth
      factor. Melanoma cells utilize this mechanism to escape from the cytotoxic effect
      of the drug. We have previously reported on the development of fully human
      neutralizing antibodies against IL-8 (anti-IL-8-monoclonal-antibody [ABX-IL8]).
      In preclinical studies, ABX-IL8 inhibited tumor growth, angiogenesis, and
      metastasis of human melanoma in vivo. We propose that combination treatment with
      dacarbazine and IL-8 will potentiate the cytotoxic effect of the drug.
      Furthermore, formation of metastasis is a multistep process that includes
      melanoma cell adhesion to endothelial cells. Melanoma cell adhesion molecule
      (MUC18) mediates these processes in melanoma and is therefore a good target for
      eliminating metastasis. We have developed a fully human antibody against MUC18
      that has shown promising results in preclinical studies. Since resistance is one
      of the major obstacles in the treatment of melanoma, we propose that utilization
      of antibodies against IL-8 or MUC18 alone, or as part of a 'cocktail' in
      combination with dacarbazine, may be a new treatment modality for metastatic
      melanoma that overcomes resistance of the disease to chemotherapy and
      significantly improves survival of patients.

PMID- 18717606
TI  - Comparative irritation potential of two combination acne products: a randomized
      controlled, subject- and evaluator-blind, comparative study in healthy
      volunteers.
AB  - BACKGROUND: Two topical 1% clindamycin/5% benzoyl peroxide combination products
      (BenzaClin [Dermik Laboratories, Inc., Bridgewater, NJ, USA] and Duac [Stiefel
      Laboratories, Coral Gables, FL, USA]) are commonly used in the treatment of mild
      to-moderate acne vulgaris. One adverse event reported with their use is local
      skin irritation. OBJECTIVE: The primary aim of this study was to compare the
      irritation potential of BenzaClin and Duac using a cumulative irritant patch test
      on healthy human skin. METHODS: A randomized controlled, subject- and evaluator
      blinded design was used to compare the cumulative irritation potential of
      BenzaClin, Duac, a positive control (0.2% sodium laurilsulfate [SLS]), and a
      negative control (white petrolatum) in healthy volunteers at a single US research
      study center. Forty subjects were enrolled and 37 completed the study. Most
      subjects were women (83%) and Caucasian (68%), and the mean age was 47 years. The
      21-day cumulative irritation patch test was used to measure the irritation
      potential of the products applied under occlusive conditions. Evaluation of
      dermal reactions to the four products was assessed visually using an ordinal
      scoring system at the time of removal of each patch. The four patches were
      applied once daily over 21 days, excluding Saturdays and Sundays, resulting in a
      total of 15 applications. The primary endpoint, determined prior to data
      collection, was mean cumulative irritation score at the end of the study on day
      22. RESULTS: At the end of the study, the mean cumulative irritation scores were
      not significantly different between BenzaClin and Duac (1.39 vs 1.36,
      respectively; p = 0.668). Both BenzaClin and Duac were significantly more
      irritating than white petrolatum and significantly less irritating than SLS (both
      p < 0.001). Based on mean cumulative irritation score, BenzaClin and Duac were
      classified as moderately irritating, SLS as highly irritating, and white
      petrolatum as not irritating. CONCLUSION: BenzaClin and Duac show similar
      propensity to cause moderate irritation compared with SLS and white petrolatum
      when applied to the skin of healthy subjects under occlusive patch conditions.

PMID- 18717607
TI  - Cosmetic acceptability of six 40-50% urea preparations: a single-blind, pilot
      study.
AB  - BACKGROUND: Urea 40-50% is widely used in the treatment of hyperkeratotic
      dermatoses. Compliance with topical therapy is directly related to the esthetic
      and sensory acceptability of a topical agent. OBJECTIVE: To assess the
      spreadability, odor, and post-application residue of 0.1 mL of six different urea
      40-50% preparations administered in single-blind fashion to 12 trained female
      panelists. METHODS: Spreadability was assessed at time 0, and odor and residue
      were assessed at 30 minutes post-application. The scores for a novel emollient
      preparation were compared with the composite scores of five existing
      preparations. RESULTS: The novel emollient preparation was found to be the most
      spreadable and to leave the least residue. Odor scores were comparable and low
      overall. CONCLUSION: Urea 40-50% preparations may vary considerably in odor,
      spreadability, and post-application residue. The novel emollient preparation was
      the most cosmetically acceptable.

PMID- 18717608
TI  - Adjuvant high-dose intravenous immunoglobulin therapy can be easily and safely
      introduced as an alternative treatment in patients with severe pemphigus
      vulgaris: a retrospective preliminary study.
AB  - BACKGROUND: Long-term corticosteroid therapy, often in association with other
      immunosuppressive agents, is considered the mainstay of pemphigus vulgaris (PV)
      therapy. Recent evidence has been changing this paradigm as patients who are non
      responsive to conventional therapies or who experience severe adverse effects
      have been successfully treated with high-dose intravenous immunoglobulin (IVIg).
      However, the shift from conventional therapies to IVIg represents a major
      challenge in the daily practice of non-experienced clinicians because of
      potential adverse effects and other issues relevant to IVIg therapy such as the
      necessity for premedication, selection of cases, modality of infusion, patient
      monitoring, and the cost and length of hospital stay. OBJECTIVE: The purpose of
      this preliminary study was to evaluate and report outcomes of treatment with IVIg
      in eight selected PV patients meeting clearly defined criteria for initiation of
      this therapy. METHODS: Available guidelines for IVIg therapy in patients with
      autoimmune mucocutaneous blistering diseases were followed. Clinical response,
      induction and duration of remission, strategies for prevention of adverse
      effects, and total days of hospital stay in eight patients with severe PV treated
      with IVIg were retrospectively evaluated. RESULTS: All patients had an effective
      clinical response without adverse reactions, leading to a significant
      corticosteroid-sparing effect. CONCLUSION: Our results indicate that, when
      current guidelines are followed, IVIg therapy can be easily and safely introduced
      as a treatment alternative in patients with severe PV. Careful monitoring of
      patients, utilization of a multidisciplinary approach, and evaluation of hospital
      related issues can help the non-experienced clinician successfully manage
      patients with severe PV requiring IVIg therapy.

PMID- 18717609
TI  - Association of psoriasis and vulval fibroepithelial polyp: first reported case.
AB  - Fibroepithelial stromal polyps of the vulvovaginal region display a wide range of
      morphologic appearances. This morphologic spectrum allows the correct diagnosis
      to be made in some cases but when histology reveals unusual features, the lesion
      may be misinterpreted as malignant. We present a case of a 35-year-old woman with
      psoriasis who developed a 15-cm polypoid lesion localized in the left labium. The
      labial lesion was resected and no recurrence was detected 12 months after the
      initial treatment. Histologically, the lesion exhibited the characteristics of a
      fibroepithelial stromal polyp with focal myxoid areas and underlying vulval
      psoriasis disease. The clinical, microscopic, and immunohistochemical findings of
      this case suggest a fibroepithelial polyp of the vulva. This vulval lesion
      represents a unique example of giant fibroepithelial stromal polyp developed in
      association with psoriasis.

PMID- 18717610
TI  - Pseudoepitheliomatous epidermal hyperplasia in tattoos: report of three cases.
AB  - Cutaneous reactions to tattoos are not uncommon and various histologic patterns
      have been reported, including lichenoid, granulomatous, eczematous, and
      pseudolymphomatous reactions. Such patterns may develop with highly variable
      delay after the tattooing procedure. We report three strikingly similar cases of
      a fast-occurring, tattoo-induced, cutaneous reaction strictly restricted to the
      red parts of the tattoos in two cases and displaying an unusual histologic
      pattern, i.e. pseudoepitheliomatous hyperplasia. Clinical differential diagnosis
      of this rare condition includes viral warts, keratoacanthoma, and verrucous
      carcinoma. It may be difficult to rule out the last two diagnoses and making the
      diagnosis usually requires full excision of the lesion, comprehensive histologic
      analysis, and careful follow-up.

PMID- 18717611
TI  - Dyschromia of hands and bronchial asthma caused by sooty molds.
AB  - Sooty molds are saprophytic fungi living on plants and feeding on honeydew
      secreted by some parasitic insects. We present a case of a 41-year-old male
      laborer who developed hypo- and hyperpigmented areas on his hands, without signs
      of inflammation or allergic reaction, together with several episodes of bronchial
      asthma, after occupational handling of sooty mold-covered citrus fruit. While
      positive prick tests to Alternaria (+++) and Cladosporium (+++) demonstrated the
      allergic nature of the patient's asthma, the pathogenic mechanism of skin
      dyspigmentation in such cases remains unknown. Hyperpigmentation could be due to
      intracutaneous penetration of a melanoid fungal pigment through repeated
      occupational microtraumatic events, while hypopigmentation could be caused by
      fungal products that are toxic/apoptosis-inducing for melanocytes and/or that
      interfere with melanogenesis (as observed for other fungi, such as Malassezia).
      This case suggests that further research is warranted in the probably
      underestimated field of sooty mold-related human diseases, and underlines the
      importance of education, use of protection devices, and prevention of sooty mold
      infestation in individuals exposed to these fungi.

PMID- 18717612
TI  - Ceftriaxone-induced fixed drug eruption: first report.
AB  - Fixed drug eruption (FDE) is an unusual type of cutaneous adverse drug reaction
      that is characterized by recurrent site-specific lesions each time the drug
      responsible is taken. FDE from cephalosporins has been rarely reported, and to
      the best of our knowledge there is no published report of ceftriaxone-induced FDE
      in the literature. We report the first case of a 54-year-old Turkish woman who
      presented with ceftriaxone-induced FDE. Topical provocation with ceftriaxone
      sodium salt (1% in water [aq.], 5% aq., 10% in petrolatum [pet.], 20% pet.)
      remained negative both at previously affected sites and in the unaffected skin of
      the back. Therapeutic re-exposure with intravenous ceftriaxone 1 g confirmed the
      diagnosis. The patient tolerated amoxicillin and cefazolin, suggesting that the
      sensitizing portion was not the beta-lactam ring. Identification of the antigenic
      determinants of FDE-inducing drugs will make predicting safe alternatives in
      patients with FDE an easier task.

PMID- 18717613
TI  - Persistent generalized lichen nitidus successfully treated with enoxaparin
      sodium.

PMID- 18717614
TI  - The state of in vitro science for use in bioaccumulation assessments for fish.
AB  - Through the concerted evaluations of thousands of commercial substances for the
      qualities of persistence, bioaccumulation, and toxicity as a result of the United
      Nations Environment Program's Stockholm Convention, it has become apparent that
      fewer empirical data are available on bioaccumulation than other endpoints and
      that bioaccumulation models were not designed to accommodate all chemical
      classes. Due to the number of chemicals that may require further assessment, in
      vivo testing is cost prohibitive and discouraged due to the large number of
      animals needed. Although in vitro systems are less developed and characterized
      for fish, multiple high-throughput in vitro assays have been used to explore the
      dietary uptake and elimination of pharmaceuticals and other xenobiotics by
      mammals. While similar processes determine bioaccumulation in mammalian species,
      a review of methods to measure chemical bioavailability in fish screening
      systems, such as chemical biotransformation or metabolism in tissue slices,
      perfused tissues, fish embryos, primary and immortalized cell lines, and
      subcellular fractions, suggest quantitative and qualitative differences between
      fish and mammals exist. Using in vitro data in assessments for whole organisms or
      populations requires certain considerations and assumptions to scale data from a
      test tube to a fish, and across fish species. Also, different models may
      incorporate the predominant site of metabolism, such as the liver, and
      significant presystemic metabolism by the gill or gastrointestinal system to help
      accurately convert in vitro data into representative whole-animal metabolism and
      subsequent bioaccumulation potential. The development of animal alternative tests
      for fish bioaccumulation assessment is framed in the context of in vitro data
      requirements for regulatory assessments in Europe and Canada.

PMID- 18717615
TI  - Evaluation of the effects of coal fly ash amendments on the toxicity of a
      contaminated marine sediment.
AB  - Approaches for cleaning up contaminated sediments range from dredging to in situ
      treatment. In this study, we discuss the effects of amending reference and
      contaminated sediments with coal fly ash to reduce the bioavailability and
      toxicity of a field sediment contaminated with polycyclic aromatic hydrocarbons
      (PAHs). Six fly ashes and a coconut charcoal were evaluated in 7-d whole sediment
      toxicity tests with a marine amphipod (Ampelisca abdita) and mysid (Americamysis
      bahia). Fly ashes with high carbon content and the coconut charcoal showed
      proficiency at reducing toxicity. Some of the fly ashes demonstrated toxicity in
      the reference treatments. It is suspected that some of this toxicity is related
      to the presence of ammonia associated with fly ashes as a result of postoxidation
      treatment to reduce nitrous oxide emissions. Relatively simple methods exist to
      remove ammonia from fly ash before use, and fly ashes with low ammonia content
      are available. Fly ashes were also shown to effectively reduce overlying water
      concentrations of several PAHs. No evidence was seen of the release of the metals
      cadmium, copper, nickel, or lead from the fly ashes. A preliminary 28-d
      polychaete bioaccumulation study with one of the high-carbon fly ashes and a
      reference sediment was also performed. Although preliminary, no evidence was seen
      of adverse effects to worm growth or lipid content or of accumulation of PAHs or
      mercury from exposure to the fly ash. These data show fly ashes with high carbon
      content could represent viable remedial materials for reducing the
      bioavailability of organic contaminants in sediments.

PMID- 18717616
TI  - Nonadditive effects in the partitioning behavior of various aliphatic and
      aromatic molecules.
AB  - Predicting the partition behavior of bifunctional molecules from their molecular
      structure is a challenge because the combination of two or more functional groups
      often has nonadditive effects. Data presented here and in the literature reveal
      that isomers of bifunctional compounds can exhibit partition constants that
      differ by several orders of magnitude. These effects are not limited to compounds
      with intramolecular H-bonds. For aliphatic molecules, large effects are found for
      diones and diesters but not for dioles. For aromatic molecules, large effects are
      found for compounds with intramolecular H-bonds and also for p-isomers with a
      strong delocalisation of pi-electrons over both functional groups as in p
      nitroaniline and p-nitrophenol. Interestingly, these nonadditive effects apply
      not only to the specific interactions but also to the van der Waals interactions
      of a molecule. This diversity of possible nonadditive effects makes it difficult
      to predict partitioning of such polyfunctional molecules. Our results suggest
      that successful models require either an extensive number of correction factors
      or a quantum chemical approach. Predicting partitioning of bifunctional molecules
      to environmental systems might face an additional complication. Unlike with
      solvents, steric limitations of natural phases may prevent them from forming
      multiple H-bonds with bifunctional molecules. Our experimental results, however,
      indicate that this situation does not occur, as the H-bond-interaction behavior
      of bifunctional molecules in humic matter and on quartz was the same as it was in
      various solvent systems.

PMID- 18717617
TI  - Is dietary mercury of neurotoxicological concern to wild polar bears (Ursus
      maritimus)?
AB  - Polar bears (Ursus maritimus) are exposed to high concentrations of mercury
      because they are apex predators in the Arctic ecosystem. Although mercury is a
      potent neurotoxic heavy metal, it is not known whether current exposures are of
      neurotoxicological concern to polar bears. We tested the hypotheses that polar
      bears accumulate levels of mercury in their brains that exceed the estimated
      lowest observable adverse effect level (20 microg/g dry wt) for mammalian
      wildlife and that such exposures are associated with subtle neurological damage,
      as determined by measuring neurochemical biomarkers previously shown to be
      disrupted by mercury in other high-trophic wildlife. Brain stem (medulla
      oblongata) tissues from 82 polar bears subsistence hunted in East Greenland were
      studied. Despite surprisingly low levels of mercury in the brain stem region
      (total mercury = 0.36 +/- 0.12 microg/g dry wt), a significant negative
      correlation was measured between N-methyl-D-aspartate (NMDA) receptor levels and
      both total mercury (r = -0.34, p < 0.01) and methylmercury (r = -0.89, p < 0.05).
      No relationships were observed among mercury, selenium, and several other
      neurochemical biomarkers (dopamine-2, gamma-aminobutyric acid type A, muscarinic
      cholinergic, and nicotinic cholinergic receptors; cholinesterase and monoamine
      oxidase enzymes). These data show that East Greenland polar bears do not
      accumulate high levels of mercury in their brain stems. However, decreased levels
      of NMDA receptors could be one of the most sensitive indicators of mercury's
      subclinical and early effects.

PMID- 18717618
TI  - Whole sediment toxicity identification evaluation tools for pyrethroid
      insecticides: III. Temperature manipulation.
AB  - Since the toxicity of pyrethroid insecticides is known to increase at low
      temperatures, the use of temperature manipulation was explored as a whole
      sediment toxicity identification evaluation (TIE) tool to help identify sediment
      samples in which pyrethroid insecticides are responsible for observed toxicity.
      The amphipod Hyalella azteca is commonly used for toxicity testing of sediments
      at a 23 degrees C test temperature. However, a temperature reduction to 18
      degrees C doubled the toxicity of pyrethroids, and a further reduction to 13
      degrees C tripled their toxicity. A similar response, though less dramatic, was
      found for 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT), and dissimilar
      temperature responses were seen for cadmium and the insecticide chlorpyrifos.
      Tests with field-collected sediments containing pyrethroids and/or chlorpyrifos
      showed the expected thermal dependency in nearly all instances. The inverse
      relationship between temperature and toxicity provides a simple approach to help
      establish when pyrethroids are the principal toxicant in a sediment sample that
      could be used as a supplemental tool in concert with chemical analysis or other
      TIE manipulations. The phenomenon appears to be, in part, a consequence of a
      reduced ability to biotransform the toxic parent compound at cooler temperatures.
      The strong dependence of pyrethroid toxicity on temperature has important
      ramifications for predicting their environmental effects, and the standard test
      temperature of 23 degrees C dramatically underestimates risk to resident fauna
      during the cooler months.

PMID- 18717619
TI  - Pulp and paper mill effluent treatments have differential endocrine-disrupting
      effects on rainbow trout.
AB  - Endocrine disruption (ED) effects due to pulp and paper mill effluents extracts
      involving different industrial procedures and effluent treatments (nontreated,
      primary, and secondary treated) were evaluated using immature triploid rainbow
      trout in a pulse-exposure toxicity experiment. The protocol involved the use of
      intraperitoneal injection of mill extracts (solid-phase extraction [SPE])
      corrected for individual fish weight and included several laboratory standards
      (steroidal hormones and phytosterols). Biological endpoints at two different
      levels of biological organization were analyzed (molecular and individual
      organism). Results indicated that nonsignificant changes were observed in the
      individual physiological indices represented by condition factor, liver somatic
      index, and gonad somatic index during the experiment. Significant induction of
      liver ethoxyresorufin-O-deethylase activity was observed between different
      effluent treatments and experimental controls. Significant endocrine-disrupting
      effects at the reproductive level were observed in all effluent treatments
      involving significant increments in plasma vitellogenin (VTG) levels. Fish
      exposed to untreated effluent extracts had significantly higher VTG levels
      compared to fish exposed to primary and secondary treatment effluent extracts,
      indicating a decrease of the estrogenic effect due to the effluent treatment. The
      present study has shown that for the Chilean pulp and paper mill SPE extracts
      evaluated, an endocrine disruption effect was induced in immature triploid
      rainbow, reaffirming the significant estrogenic effects demonstrated previously
      in laboratory and field experiments.

PMID- 18717620
TI  - Ammonia sensitivity of the glass eel (Anguilla anguilla L.): salinity dependence
      and the role of branchial sodium/potassium adenosine triphosphatase.
AB  - Eel aquaculture is capture based and thus dependent on the fishery for juvenile
      glass eels. This fishery typically takes place in estuaries where salinity varies
      and ammonia levels can be elevated. Also, during capture and transport glass eels
      are kept at high densities and ammonia from endogenous production can increase to
      toxic levels. Ammonia is known to have detrimental effects on fish growth and
      survival. In the present study, the salinity dependence of ammonia sensitivity in
      glass eels acclimated to either seawater or freshwater was determined, and the
      possible role of branchial sodium/potassium adenosine triphosphatase (Na+/K+ 
      ATPase) was investigated. Freshwater-acclimated glass eels were found to be more
      sensitive to ammonia with a lethal concentration to 50% of the test organisms
      (LC50) value for 96 h of 3.30 mM for total ammonia nitrogen (TAN) and 117 microM
      for un-ionized ammonia (UIA), versus values of 4.95 mM and 138 microM,
      respectively, for seawater-acclimated animals. Freshwater glass eels also had
      significantly lower body TAN levels than seawater-acclimated glass eels, although
      body accumulation profiles during exposure were similar. The higher branchial
      Na+/K+ -ATPase activities in seawater glass eels might explain this difference in
      sensitivity; however, activities decreased significantly with increasing ammonia
      levels. There was also no salinity dependence of net ammonia flux rates (0.388
      micromol of TAN/g/h). Holding glass eels at high densities characteristic of
      transport conditions resulted in elevated ammonia concentrations to approximately
      3 mM, which coincidently approaches to the freshwater LC50 value and may
      therefore contribute to mortality.

PMID- 18717621
TI  - Biotransformation of acridine by Mycobacterium vanbaalenii.
AB  - Cultures of Mycobacterium vanbaalenii strain PYR-1 in a liquid medium were
      exposed to the toxic environmental contaminant acridine (260 microM). After
      incubation for 7 d, the cultures were extracted with ethyl acetate. Metabolites
      were purified using high-performance liquid chromatography and analyzed by mass
      spectrometry and 1H nuclear magnetic resonance spectroscopy. Four metabolites,
      9,10-dihydroacridine, 4-hydroxyacridine, acridine cis-1 ,2-dihydrodiol, and
      acridin-9(10H)-one, were identified.

PMID- 18717622
TI  - Evaluation of estrogenic activity of parabens and their chlorinated derivatives
      by using the yeast two-hybrid assay and the enzyme-linked immunosorbent assay.
AB  - We assessed the estrogen agonist activities of 21 parabens and their chlorinated
      derivatives by using yeast two-hybrid assays incorporating either the human or
      medaka (Oryzias latipes) estrogen receptor alpha (hERalpha and medERalpha,
      respectively), and by using hERalpha competitive enzyme-linked immunosorbent
      assay (ER-ELISA). In the two-hybrid assay with hERalpha, five parabens and three
      chlorinated derivatives exhibited estrogenic activity, and their relative
      activity (17beta-estradiol [E2] = 1) ranged from 2.0 x 10(-5) to 2.0 x 10(-4),
      with the highest activity observed in i-butylparaben. In the medERalpha assay,
      six parabens and six chlorinated derivatives exhibited estrogenic activity and
      their relative activity ranged from 2.7 x 10(-5) to 3.5 x 10(-3), with the
      highest activity observed in benzylparaben, its monochlorinated derivative, i
      butylparaben, and n-butylparaben. Although medERalpha demonstrated an activity to
      E2 that was three times lower than that demonstrated by hERalpha, medERalpha has
      a higher sensitivity to parabens than hERa (1.3-8.9 times). Five parabens and two
      chlorinated derivatives exhibited a binding affinity to ERa in the ER-ELISA; of
      the parabens, i-butylparaben exhibited the strongest binding affinity. The yeast
      two-hybrid assay and the ER-ELISA also revealed that many of the assayed
      chlorinated parabens were much weaker than the parent compound. In addition, the
      results mainly showed that parabens with a bulk substituent (e.g., i-butyl and
      benzyl groups) had a higher activity than those with a sterically small
      substituent. It is considered that derivatization masks the apparent estrogenic
      activity of parabens, but the resulting chlorinated compounds may represent a
      potential hazard and therefore other toxicity tests should be performed to
      determine the toxicity of the chlorinated derivatives.

PMID- 18717623
TI  - Antibiotics as a chemical stressor affecting an aquatic decomposer-detritivore
      system.
AB  - Recent evidence indicates that a variety of antibiotic residues may affect the
      integrity of streams located downstream from wastewater treatment plants. Aquatic
      communities comprising bacterial and fungal decomposers and invertebrate
      detritivores (shredders) play an important role in the decomposition of
      allochthonous leaf litter, which acts as a primary energy source for small
      running waters. The aim of the present study was to assess whether an antibiotic
      mixture consisting of sulfamethoxazole, trimethoprim, erythromycin-H2O,
      roxithromycin, and clarithromycin has an effect on such a decomposer-detritivore
      system. Leaf discs were exposed to these antibiotics (total concentration of 2 or
      200 microg/L) for approximately 20 d before offering these discs and
      corresponding control discs to an amphipod shredder, Gammarus fossarum, in a food
      choice experiment. Gammarus preferred the leaf discs conditioned in the presence
      of the antibiotic mixture at 200 microg/L over the control discs (pair-wise t
      test; p = 0.006). A similar tendency, while not significant, was observed for
      leaves conditioned with antibiotics at a concentration of 2 microg/L. The number
      of bacteria associated with leaves did not differ between treatments at either
      antibiotic concentration (t test; p = 0.57). In contrast, fungal biomass
      (measured as ergosterol) was significantly higher in the 200 microg/L treatment
      (t test; p = 0.038), suggesting that the preference of Gammarus may be related to
      a shift in fungal communities. Overall these results indicate that mixtures of
      antibiotics may disrupt important ecosystem processes such as organic matter flow
      in stream ecosystems, although effects are likely to be weak at antibiotic
      concentrations typical of streams receiving wastewater treatment plant effluents.

PMID- 18717624
TI  - Polybrominated diphenyl ether congener patterns, hexabromocyclododecane, and
      brominated biphenyl 153 in eggs of peregrine falcons (Falco peregrinus) breeding
      in Sweden.
AB  - Previous analyses of 52 peregrine falcon (Falco peregrinus) eggs collected from
      two wild and one captive population in Sweden 1987 through 1999 were complemented
      by including additional polybrominated diphenyl ether (PBDE) congeners (BDE-35, 
      183, -184, -185, -196, -197, -203, and -207). In addition, 31 eggs not previously
      analyzed for hexabromocyclododecane (HBCD) and BDE-209 were analyzed for these.
      Geometric mean concentrations of BPBDEs, HBCD, and the hexabrominated biphenyl
      (BB-153) were 3,100, 140, and 81 ng/g of lipid weight for the southern
      population; 2,500, 110, and 84 ng/g of lipid weight for the northern population;
      and 47, not detected, and 8 ng/g of lipid weight for the captive population. The
      BDE congener pattern was dominated by BDE-153, -99, and -100. The results were
      used to investigate whether a difference in PBDE congener pattern could be
      distinguished between the two wild populations of peregrine falcons due to
      different diets, as the southern population preys mainly on birds belonging to
      the terrestrial food chain while the northern population preys more on aquatic
      birds. A multivariate t-test showed a subtle but significant (p < 0.001)
      difference in PBDE congener pattern between the two populations. However, our
      hypothesis that higher-brominated congeners of PBDEs would be present to a
      greater extent in the terrestrial food chain was not supported by principal
      component analysis. The average brood size for individual females from the
      southern population decreased with increasing concentrations of IPBDE in the eggs
      (log-linear regression p < 0.01).

PMID- 18717625
TI  - Oxidative stress and DNA damage in broad bean (Vicia faba L.) seedlings induced
      by thallium.
AB  - Thallium (Tl) is a metal of great toxicological concern because it is highly
      toxic to all living organisms through mechanisms that are yet poorly understood.
      Since Tl is accumulated by important crops, the present study aimed to analyze
      the biological effects induced by bioaccumulation of Tl in broad bean (Vicia faba
      L.) as well as the plant's antioxidative defense mechanisms usually activated by
      heavy metals. Thallium toxicity was related to production of reactive oxygen
      species in leaves and roots of broad bean seedlings following short-term (72 h)
      exposure to thallium (I) acetate (0, 0.5, 1, 5, and 10 mg/L) by evaluating DNA
      damage and oxidative stress parameters as well as antioxidative response. The
      possible antagonistic effect of potassium (K) was tested by combined treatment
      with 5 mg/L of Tl (Tl+) and 10 mg/L of potassium (K+) acetate. Accumulation of
      Tl+ in roots was 50 to 250 times higher than in broad bean shoots and was
      accompanied by increase in dry weight and proline. Despite responsive
      antioxidative defense (increased activities of superoxide dismutase, ascorbate
      peroxidase, and pyrogallol peroxidase), Tl+ caused oxidative damage to lipids and
      proteins as evaluated by malondialdehyde and carbonyl group levels, and induced
      DNA strand breaks. Combined treatment caused no oxidative alternations to lipids
      and proteins though it induced DNA damage. The difference in Tl-induced
      genotoxicity following both acellular and cellular exposure implies indirect DNA
      damage. Results obtained indicate that oxidative stress is involved in the
      mechanism of Tl toxicity and that the tolerance of broad bean to Tl is achieved,
      at least in part, through the increased activity of antioxidant enzymes.

PMID- 18717626
TI  - Energy and water flux during terrestrial estivation and overland movement in a
      freshwater turtle.
AB  - The doubly labeled water (DLW) method for studying energy and water balance in
      field-active animals is not feasible for freshwater animals during aquatic
      activities, but several species of nominally aquatic reptiles leave wetlands for
      several critical and extended behaviors, where they face challenges to their
      energy and water balance. Using DLW, we studied energy and water relations during
      terrestrial estivation and movements in the eastern long-necked turtle (Chelodina
      longicollis), a species that inhabits temporary wetlands in southeastern
      Australia. Water efflux rates of 14.3-19.3 mL (kg d)(-1 ) during estivation were
      nearly offset by influx, indicating that turtles did not maintain water balance
      while terrestrial, though dehydration was slow. Estivation energy expenditure
      declined over time to 20.0-24.6 kJ (kg d)(-1) but did not indicate substantial
      physiological specializations. Energy reserves are predicted to limit survival in
      estivation to an estimated 49-261 d (depending on body fat), which is in close
      agreement with observed bouts of natural estivation in this population. The
      energy cost and water flux rates associated with overland movement behavior
      ranged from 46 to 99 kJ (kg d)(-1 ) and from 21.6 to 40.6 mL (kg d)(-1),
      respectively, for turtles moving 23-34 m d(-1). When a wetland dries, a turtle
      that forgoes movement to other wetlands can save sufficient energy to fuel up to
      134 d in estivation. The increasing time in estivation with travel distance
      gained in this energy "trade-off" fits our previous observations that more
      turtles estivate when longer distances must be traveled to the nearest permanent
      lake, whereas emigration is nearly universal when only short distances must be
      traversed. The DLW method shows promise for addressing questions regarding the
      behavioral ecology and physiology of freshwater turtles in terrestrial
      situations, though validation studies are needed.

PMID- 18717627
TI  - Inhibition of ref-1 stimulates the production of reactive oxygen species and
      induces differentiation in adult cardiac stem cells.
AB  - Redox effector protein-1 (Ref-1) plays an essential role in DNA repair and redox
      regulation of several transcription factors. In the present study, we examined
      the role of Ref-1 in maintaining the redox status and survivability of adult
      cardiac stem cells challenged with a subtoxic level of H2O2 under inhibition of
      Ref-1 by RNA interference. Treatment of cardiac stem cells with a low
      concentration of H2O2 induced Ref-1-mediated survival signaling through
      phosphorylation of Akt. However, Ref-1 inhibition followed by H2O2 treatment
      extensively induced the level of intracellular reactive oxygen species (ROS)
      through activation of the components of NADPH oxidase, like p22( phox ), p47(
      phox ), and Nox4. Cardiac differentiation markers (Nkx2.5, MEF2C, and GATA4), and
      cell death by apoptosis were significantly elevated in Ref-1 siRNA followed by
      H2O2-treated stem cells. Further, inhibition of Ref-1 increased the level of p53
      but decreased the phosphorylation of Akt, a molecule involved in survival
      signaling. Treatment with ROS scavenger N-acetyl-L-cysteine attenuated Ref-1
      siRNA-mediated activation of NADPH oxidase and cardiac differentiation. Taken
      together, these results indicate that Ref-1 plays an important role in
      maintaining the redox status of cardiac stem cells and protects them from
      oxidative injury-mediated cell death and differentiation.

PMID- 18717628
TI  - Oxidative stress involvement in alpha-synuclein oligomerization in Parkinson's
      disease cybrids.
AB  - Mitochondrial dysfunction, oxidative stress, and alpha-synuclein oligomerization
      occur in Parkinson disease (PD). We used an in vitro PD cybrid approach that
      models these three phenomena specifically to evaluate the impact of mitochondria
      derived oxidative stress on alpha-synuclein oligomerization. Compared with
      control cybrid cell lines, reactive oxygen species (ROS) production and protein
      oxidative stress markers were elevated in PD cybrids. The antioxidants CoQ(10)
      and GSH attenuated changes in PD cybrid peroxide, protein carbonyl, and protein
      sulfhydryl levels. Elevated PD cybrid alpha-synuclein oligomer levels were also
      attenuated by CoQ(10) and GSH. In PD cybrids, alpha-synuclein oligomerization was
      activated via a complex I-mediated increase in the free tubulin/polymerized
      tubulin ratio. CoQ(10) but not GSH increased complex I activity, restored ATP to
      control levels, and normalized the PD cybrid free tubulin/polymerized tubulin
      ratio. Overall, we conclude that two different antioxidants can decrease alpha
      synuclein oligomerization whether by improving mitochondrial function or by
      preventing protein carbonylation or both. We conclude that mitochondrial
      dysfunction can induce alpha-synuclein oligomerization via ATP depletion-driven
      microtubule depolymerization and via ROS increase-driven protein oxidation.

PMID- 18717629
TI  - The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative
      disease.
AB  - Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to
      induce expression of a variety of cytoprotective and detoxification genes.
      Several of the genes commonly regulated by Nrf2 have been implicated in
      protection from neurodegenerative conditions. Work from several laboratories has
      uncovered the potential for Nrf2-mediated transcription to protect from
      neurodegeneration resulting from mechanisms involving oxidative stress. For this
      reason, Nrf2 may be considered a therapeutic target for conditions that are known
      to involve free radical damage. Because common mechanisms of neurodegeneration,
      such as mitochondrial dysfunction and build-up of reactive oxygen species, are
      currently being uncovered, targeting Nrf2 may be valuable in combating conditions
      with variable causes and etiologies. Most effectively to target this protein in
      neurodegenerative conditions, a description of the involvement of Nrf2 and
      potential for neuroprotection must come from laboratory models. Herein, we review
      the current literature that suggests that Nrf2 may be a valuable therapeutic
      target for neurodegenerative disease, as well as experiments that illustrate
      potential mechanisms of protection.

PMID- 18717631
TI  - Transcribe to survive: transcriptional control of antioxidant defense programs
      for neuroprotection in Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive, primarily motor disorder that is
      characterized by loss of dopaminergic (DA) neurons within the substantia nigra
      (SN). Cell death in PD has been associated with impaired mitochondrial function
      and increased oxidative stress. Strategies to reduce the oxidative load in DA
      cells may be beneficial in slowing the progression of PD. The transcription
      factor nuclear factor-erythroid 2 (NF-E2) related factor 2 (NRF2) is emerging as
      a master regulator of antioxidant defense systems, which makes it an attractive
      target for manipulations that aim to increase cellular resistance to oxidative
      stress. Peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator
      1 alpha (PGC1alpha) is a regulator of mitochondrial biogenesis genes that
      simultaneously upregulates many genes known to protect against oxidative stress.
      Pgc-1alpha knockout mice show enhanced susceptibility to SN neuronal loss
      following MPTP exposure, whilst overexpression of Pgc-1alpha appears to protect
      against oxidative stress in vitro. This makes PGC-1alpha a highly attractive
      target for neuroprotective therapies in PD. This review will explore the
      mechanisms behind the induction of NRF2 and PGC-1alpha in response to oxidative
      stress and identify common pathways that may provide targets for upregulating
      antioxidant defense programs.

PMID- 18717635
TI  - Latitudinal trends in digestive flexibility: testing the climatic variability
      hypothesis with data on the intestinal length of rodents.
AB  - Flexibility of digestive features can be understood considering the benefits of
      digestion, which links animal foraging to metabolizable energy and nutrient gain,
      and its costs, which are partly indexed by digestive tract tissue mass, one of
      the most expensive to maintain in terms of energy and protein metabolism. In this
      article, we applied a meta-analytical approach to current data on rodents' small
      intestine length flexibility to evaluate the climatic variability hypothesis
      (CVH). This hypothesis states the following: (1) as the range of climatic
      fluctuation experienced by terrestrial animals increases with latitude,
      individuals at higher latitudes should be more flexible to persist at a site; (2)
      the greater phenotypic flexibility allows species to occupy more habitats and to
      become more widely distributed. We compiled data from 25 articles, which provided
      a total of 86 estimations of flexibility involving 20 rodent species. Consistent
      with CVH predictions, we found a positive correlation between small intestine
      length flexibility and latitude and between small intestine length flexibility
      and the number of habitats occupied by different species. When seen from the
      perspective of digestive physiology, our analysis is an important piece of
      evidence on the adaptive value of digestive flexibility in small mammals.

PMID- 18717636
TI  - Competition-similarity relationships and the nonlinearity of competitive effects
      in consumer-resource systems.
AB  - Much previous ecological and evolutionary theory about exploitative competition
      for a continuous spectrum of resources has used the Lotka-Volterra model with
      competition coefficients given by a Gaussian function of niche separation. Using
      explicit consumer-resource models, we show that the Lotka-Volterra model and the
      assumption of a Gaussian competition-similarity relationship both fail to reflect
      the impact of strong resource depletion, which typically reduces the influence of
      the most heavily used resources on the competitive interaction. Taking proper
      account of resource depletion reveals that strong exploitative competition
      between efficient consumers is usually a highly nonlinear interaction, implying
      that a single measure is no longer sufficient to characterize the process. The
      nonlinearity usually entails weak coupling of competing species when their
      abundances are high and equal. Rare invaders are likely to have effects on
      abundant residents much larger than those of the resident on the invader.
      Asymmetrical utilization curves often produce asymmetrical competition
      coefficients. Competition coefficients are typically non-Gaussian and are often
      nonmonotonic functions of niche separation. Utilization curve shape and resource
      growth functions can have major effects on competition-similarity relationships.
      A variety of previous theoretical findings need to be reassessed in light of
      these results.

PMID- 18717637
TI  - The impact of steroids given with macrolide therapy on experimental Mycoplasma
      pneumoniae respiratory infection.
AB  - BACKGROUND: Systemic steroids have been advocated in addition to antimicrobial
      therapy for severe Mycoplasma pneumoniae pneumonia. We evaluated the efficacy of
      clarithromycin, dexamethasone, and combination therapy for M. pneumoniae
      respiratory infection. METHODS: Mice infected with M. pneumoniae were treated
      with clarithromycin, dexamethasone, combined clarithromycin/dexamethasone, or
      placebo daily; mice were evaluated at baseline and after 1, 3, and 6 days of
      therapy. Outcome variables included M. pneumoniae culture, lung histopathologic
      score (HPS), and bronchoalveolar lavage cytokine, chemokine, and growth factor
      concentrations. RESULTS: Clarithromycin monotherapy resulted in the greatest
      reductions in M. pneumoniae concentrations. After 3 days of treatment,
      combination therapy significantly reduced lung HPS compared with placebo,
      clarithromycin, and dexamethasone alone, whereas, after 6 days of therapy,
      clarithromycin alone and combination therapy significantly reduced lung HPS
      compared with placebo. Concentrations of interleukin (IL)-12 p40, RANTES,
      macrophage chemotactic protein-1, and cytokine-induced neutrophil chemoattractant
      were significantly lower in mice treated with clarithromycin alone and/or
      combination therapy compared with dexamethasone alone and/or placebo; combination
      therapy resulted in a significantly greater reduction than clarithromycin alone
      for IL-12 p40 and RANTES. CONCLUSIONS: Although monotherapy with clarithromycin
      had the greatest effect on reducing concentrations of M. pneumoniae, combination
      therapy had the greatest effect on decreasing levels of cytokines and chemokines
      as well as pulmonary histologic inflammation.

PMID- 18717638
TI  - Comparison of the diversity of the vaginal microbiota in HIV-infected and HIV
      uninfected women with or without bacterial vaginosis.
AB  - BACKGROUND: Whether human immunodeficiency virus (HIV) infection is associated
      with a change in the diversity of genital microbiota in women was investigated.
      METHODS: Amplicon length heterogeneity polymerase chain reaction (LH-PCR)
      analysis and pyrosequencing of the 16S ribosomal RNA gene were used to analyze
      the diversity of the microbiota in HIV-positive (HIV(+)) and HIV-negative (HIV(
      )) women with or without bacterial vaginosis (BV). RESULTS: LH-PCR analysis
      revealed significantly more microbiota diversity in BV-positive (BV(+)) women
      than in BV-negative (BV(-)) women, but no significant difference was noted
      between HIV(+) women and HIV(-) women. Pyrosequencing revealed that Lactobacillus
      organisms constituted a median of 96% of the bacteria in BV(-) women. BV(+) women
      had a significantly higher number of taxa found at > or =1% of the total genital
      microbiota (median, 11 taxa). Common taxa in BV(+) women were Prevotella,
      Megasphaera, Gardnerella, Coriobacterineae, Lachnospira, and Sneathia. There was
      a trend (P = .07) toward the presence of a higher number of taxa in HIV(+)BV(+)
      women than in HIV(-)BV(+) women. Propionibacterineae, Citrobacter, and
      Anaerococcus were the taxa found only in HIV(+) women (P < .05). CONCLUSIONS: The
      present study demonstrated that both LH-PCR analysis and pyrosequencing
      differentiated microbiota in BV(+) women from that in BV(-) women and that
      pyrosequencing indicated a trend toward increased diversity in BV(+)HIV(+) women,
      suggesting that HIV infection is associated with changes in the diversity of
      genital microbiota.

PMID- 18717639
TI  - Acquisition of invasion-inhibitory antibodies specific for the 19-kDa fragment of
      merozoite surface protein 1 in a transmigrant population requires multiple
      infections.
AB  - Antibodies against the 19 kDa C-terminal fragment of merozoite surface protein 1
      (MSP1(19)) are a major component of the invasion-inhibitory response in
      individuals immune to malaria. We report here the acquisition of MSP1(19)
      specific invasion-inhibitory antibodies in a group of transmigrants who
      experienced their sequential malaria infections during settlement in an area of
      Indonesia where malaria is highly endemic. We used 2 transgenic Plasmodium
      falciparum parasite lines that expressed either endogenous MSP1(19) or the
      homologous region from P. chabaudi to measure the MSP1(19)-specific invasion
      inhibitory antibodies. The results revealed that the acquisition of MSP1(19)
      specific invasion-inhibitory antibodies required 2 or more P. falciparum
      infections. In contrast, enzyme-linked immunosorbent assays on the same serum
      samples showed that MSP1(19)-specific antibodies are present after the first
      malaria infection. This delay in the acquisition of functional antibodies by
      residents of areas where malaria is endemic is consistent with the observation
      that multiple malaria infections are required before clinical immunity is
      acquired.

PMID- 18717640
TI  - High heritability but uncertain mode of inheritance for total serum IgE level and
      Schistosoma mansoni infection intensity in a schistosomiasis-endemic Brazilian
      population.
AB  - BACKGROUND: Evidence of genetic control for total serum IgE (tIgE) level has been
      reported in multiple populations, although populations with substantial exposure
      to helminths have yielded lower estimates of heritability, despite evidence
      suggesting that genes also control a significant portion of the variation in the
      number of Schistosoma mansoni eggs per gram of fecal matter. METHODS: By use of a
      whole-population ascertainment scheme, 822 individuals were enrolled from a
      schistosomiasis-endemic area in Conde, Bahia, in Brazil. Heritability was
      estimated by using an additive polygenic model, and segregation analysis was
      performed for 2 quantitative traits, tIgE level and egg count. RESULTS: After
      adjusting for nongenetic covariates, the heritability of log-transformed tIgE
      level and log-transformed egg count was estimated at 60% and 31%, respectively.
      No evidence for a single major gene controlling tIgE level or egg count was
      observed in segregation analysis for 781 individuals and 403 individuals,
      respectively, in 318 families, however, which suggests complex biological
      control. CONCLUSIONS: The high heritability of tIgE level indicates that genetic
      factors are likely to control tIgE level even in the presence of helminthic
      infection. Substantial heritability for the burden of S. mansoni infection was
      confirmed in these Brazilian families. Further genetic studies will be needed to
      dissect the specific genetic factors that underlie these traits.

PMID- 18717641
TI  - Graft vascular disease: immune response meets the vessel wall.
AB  - Graft vascular disease (GVD) is the single most important long-term limitation to
      solid-organ transplantation. It is a concentric vascular intimal hyperplastic
      lesion composed of smooth muscle-like cells and associated matrix. GVD diffusely
      involves allograft vessels, eventually compromising perfusion and resulting in
      graft ischemia and failure. Animal models and an increasing sophistication in
      analyzing human GVD have provided important new insights into GVD pathogenesis.
      Innate and specific immune responses both participate in the initial vascular
      injury; GVD develops as a consequence of downstream chemokine- and cytokine
      effector pathways. Other significant developments in the field include
      recognition of the central pathogenic role played by interferon-gamma as well as
      the contribution of host cell precursors to the intimal lesions. Because GVD
      shares many features with more common vascular pathologies, insights gleaned from
      our understanding of allograft vasculopathy may well impact our treatment for
      "traditional" atherosclerosis or restenosis lesions.

PMID- 18717642
TI  - Soluble factors-mediated immunomodulatory effects of canine adipose tissue
      derived mesenchymal stem cells.
AB  - Adipose tissue-derived mesenchymal stem cells (AD-MSCs), which can differentiate
      into several lineages, have immunomodulatory properties similar to those of bone
      marrow-derived MSCs. However, the specific mechanism by which the
      immunomodulatory effect of MSCs occurs is not clear. In this study, we isolated
      canine AD-MSCs (cAD-MSCs) and induced their development into adipocyte,
      osteocyte, and neuron-like cells. We then investigated their phenotype and
      cytokine expression to determine whether they were able to exert an
      immunomodulatory effect and what the underlying mechanisms of this effect were.
      cAD-MSCs expressed CD44, CD90, and MHC class I and were also partially positive
      for the expression of CD34; however, they did not express CD14 and CD45. In
      addition, they expressed the mRNA of transforming growth factor beta (TGF-beta),
      IL-6, IL-8, CCL2, CCL5, vascular endothelial growth factor, hepatocyte growth
      factor (HGF), tissue inhibitor metalloproteinase-1/2, and cyclooxygenase-2 but
      not that of IL-10. Further, leukocyte proliferation induced by mitogens was
      suppressed when they were cocultured with irradiated cAD-MSCs, as well as with
      culture supernatants of cAD-MSCs alone. Moreover, TNF-alpha production
      significantly decreased, whereas TGF-beta, IL-6, and interferon-gamma production
      significantly increased in cAD-MSCs that were cocultured with leukocytes.
      Finally, immonomodulatory factors of MSCs, such as TGF-beta, HGF, prostaglandin
      E2 (PGE2), and indoleamine 2, 3 dioxygenase (IDO), increased significantly in cAD
      MSCs that were cocultured with leukocytes; however, the production of PGE2 and
      IDO showed different kinetics, and leukocyte proliferation was effectively
      restored by PGE2 and IDO inhibitors. Taken together, these results indicate that
      the immunomodulatory effects of cAD-MSCs are associated with soluble factors (TGF
      beta, HGF, PGE2, and IDO). Therefore, it is suggested that cAD-MSCs have a
      potential therapeutic use in the treatment of immune-mediated disease.

PMID- 18717643
TI  - Gene expression profiling-based in silico approach to identify potential vaccine
      candidates and drug targets against B. pertussis and B. parapertussis.
AB  - Whooping cough (pertussis) caused by B. pertussis (B.p) is still serious public
      health threat. B. parapertussis (B.pp), closely related to B.p, also causes
      whooping cough. The incidence of B.pp infections has been increasing over the
      last decades, partly because pertussis vaccines have low efficiency against B.pp
      infections. Moreover, because the majority of pertussis patients are infants,
      common antimicrobial agents producing serious adverse reactions in infants are
      not fully satisfactory. Therefore, we try to identify potential vaccine
      candidates and alternative drug targets against both B.p and B.pp. This
      preliminary work integrates several different kinds of data from in silico
      analysis, comparative genomic hybridization, global transcriptional profiling,
      and protein-protein interaction (PPI) network to screen potential vaccine
      candidates and drug targets against the two species. Finally, 191 potential
      crossprotective vaccine candidates are identified. They have high transcriptional
      levels in both species, or are associated with virulence and pathogenesis.
      Moreover, these proteins are not only potentially surface-exposed in the
      bacteria, but also well conserved among the 165 B.p and B.pp strains. Among them,
      22 candidates with high essentiality in the two PPI networks of B.p and B.pp are
      regarded as suitable drug targets against the two species. We just selected
      Bordetella as an example to develop a rapid and reliable approach for screening
      alternative drug targets that associated with novel protein pathways, complexes,
      and cellular functions against these antibiotic-resistant pathogens. Further
      researches focusing on the 191 vaccine candidates could accelerate the
      development of more effective vaccines and drug therapy against B.p and B.pp
      infection.

PMID- 18717645
TI  - Stimulation by lithium of the interaction between the transcription factor CREB
      and its co-activator TORC.
AB  - Lithium salts are clinically important drugs used to treat bipolar mood disorder.
      The mechanisms accounting for the clinical efficacy are not completely
      understood. Chronic treatment with lithium is required to establish mood
      stabilization, suggesting the involvement of neuronal plasticity processes. CREB
      (cAMP-response-element-binding protein) is a transcription factor known to
      mediate neuronal adaptation. Recently, the CREB-co-activator TORC (transducer of
      regulated CREB) has been identified as a novel target of lithium and shown to
      confer an enhancement of cAMP-induced CREB-directed gene transcription by
      lithium. TORC is sequestered in the cytoplasm and its nuclear translocation
      controls CREB activity. In the present study, the effect of lithium on TORC
      function was investigated. Lithium affected neither the nuclear translocation of
      TORC nor TORC1 transcriptional activity, but increased the promoter occupancy by
      TORC1 as revealed by chromatin immunoprecipitation assay. In a mammalian two
      hybrid assay, as well as in a cell-free GST (glutathione transferase) pull-down
      assay, lithium enhanced the CREB-TORC1 interaction. Magnesium ions strongly
      inhibited the interaction between GST-CREB and TORC1 and this effect was reversed
      by lithium. Thus our results suggest that, once TORC has entered the nucleus,
      lithium as a cation stimulates directly the binding of TORC to CREB, leading to
      an increase in cAMP-induced CREB target-gene transcription. This novel mechanism
      of lithium action is likely to contribute to the clinical mood-stabilizing effect
      of lithium salts.

PMID- 18717644
TI  - In vivo delivery of bionanocapsules displaying Phaseolus vulgaris agglutinin-L4
      isolectin to malignant tumors overexpressing N-acetylglucosaminyltransferase V.
AB  - Metastasis is a key aspect of tumor malignancy, and several malignant tumors show
      expression of various mature N-type glycans. In particular, beta1-6 branching N
      acetylglucosamine (GlcNAc) is abundantly expressed as a part of high-mannose
      glycans in various highly metastatic cancers. Phaseolus vulgaris agglutinin-L(4)
      isolectin (L(4)-PHA), which adheres to beta1-6 GlcNAc specifically, has been used
      for in situ cancer diagnosis. Bionanocapsules (BNCs), hollow particles with a
      diameter of approximately 80 nm and composed of hepatitis B surface antigen
      (HBsAg) and a lipid bilayer, have been developed as human liver-specific
      nanocapsules for in vivo drug delivery system. In this study, we have generated
      L(4)-PHA-displaying BNCs (PHA-BNCs) and examined whether L(4)-PHA could retarget
      the BNCs to malignant tumors as a "biosensor" distinguishing tumor metastaticity.
      Fluorescence-labeled PHA-BNCs injected systemically into a mouse xenograft model
      were found to accumulate in beta1-6 GlcNAc-expressing malignant tumors. The PHA
      BNCs were able to deliver DNA to the malignant cancer cells. These results open
      up the possibility of using L(4)-PHA lectin as a targeting molecule in a drug
      delivery system, and of using PHA-BNCs as a novel nanodevice for malignant tumor
      specific bioimaging and drug delivery.

PMID- 18717646
TI  - Role of AQP2 during apoptosis in cortical collecting duct cells.
AB  - BACKGROUND INFORMATION: A major hallmark of apoptosis is cell shrinkage, termed
      apoptotic volume decrease, due to the cellular outflow of potassium and chloride
      ions, followed by osmotically obliged water. In many cells, the ionic pathways
      triggered during the apoptotic volume decrease may be similar to that observed
      during a regulatory volume decrease response under hypotonic conditions. However,
      the pathways involved in water loss during apoptosis have been largely ignored.
      It was recently reported that in some systems this water movement is mediated via
      specific water channels (aquaporins). Nevertheless, it is important to identify
      whether this is a ubiquitous aspect of apoptosis as well as to define the
      mechanisms involved. The aim of the present work was to investigate the role of
      aquaporin-2 during apoptosis in renal-collecting duct cells. We evaluated the
      putative relationship between aquaporin-2 expression and the activation of the
      ionic pathways involved in the regulatory volume response. RESULTS: Apoptosis was
      induced by incubating cells with a hypertonic solution or with cycloheximide in
      two cortical collecting duct cell lines: one not expressing aquaporins and the
      other stably transfected with aquaporin-2. Typical features of apoptosis were
      evaluated with different approaches and the water permeability was measured by
      fluorescence videomicroscopy. Our results show that the rate of apoptosis is
      significantly increased in aquaporin-2 cells and it is linked to the rapid
      activation of volume-regulatory potassium and chloride channels. Furthermore, the
      water permeability of cells expressing aquaporin-2 was strongly reduced during
      the apoptotic process and it occurs before DNA degradation. CONCLUSIONS: These
      results let us propose that under apoptotic stimulation aquaporin-2 would act as
      a sensor leading to a co-ordinated activation of specific ionic channels for
      potassium and chloride efflux, resulting in both more rapid cell shrinkage and
      more rapid achievement of adequate levels of ions necessary to activate the
      enzymatic apoptotic cascade.

PMID- 18717647
TI  - Regulation and function of triacylglycerol lipases in cellular metabolism.
AB  - The ability to store energy in the form of energy-dense TAG (triacylglycerol) and
      to mobilize these stores rapidly during times of low carbohydrate availability
      (fasting or famine) or during heightened metabolic demand (exercise or cold
      stress) is a highly conserved process essential for survival. Today, in the
      presence of nutrient excess and sedentary lifestyles, the regulation of this
      pathway is viewed as an important therapeutic target for disease prevention, as
      elevated circulating fatty acids in obesity contribute to many aspects of the
      metabolic syndrome including hepatic steatosis, atherosclerosis and insulin
      resistance. In the present review, we discuss the metabolic regulation and
      function of TAG lipases with a focus on HSL (hormone-sensitive lipase), ATGL
      (adipose triacylglycerol lipase) and newly identified members of the lipolytic
      proteome.

PMID- 18717648
TI  - Regulation of gene expression in the nervous system.
AB  - The nervous system contains a multitude of cell types which are specified during
      development by cascades of transcription factors acting combinatorially. Some of
      these transcription factors are only active during development, whereas others
      continue to function in the mature nervous system to maintain appropriate gene
      expression patterns in differentiated cells. Underpinning the function of the
      nervous system is its plasticity in response to external stimuli, and many
      transcription factors are involved in regulating gene expression in response to
      neuronal activity, allowing us to learn, remember and make complex decisions.
      Here we review some of the recent findings that have uncovered the molecular
      mechanisms that underpin the control of gene regulatory networks within the
      nervous system. We highlight some recent insights into the gene-regulatory
      circuits in the development and differentiation of cells within the nervous
      system and discuss some of the mechanisms by which synaptic transmission
      influences transcription-factor activity in the mature nervous system. Mutations
      in genes that are important in epigenetic regulation (by influencing DNA
      methylation and post-translational histone modifications) have long been
      associated with neuronal disorders in humans such as Rett syndrome, Huntington's
      disease and some forms of mental retardation, and recent work has focused on
      unravelling their mechanisms of action. Finally, the discovery of microRNAs has
      produced a paradigm shift in gene expression, and we provide some examples and
      discuss the contribution of microRNAs to maintaining dynamic gene regulatory
      networks in the brain.

PMID- 18717649
TI  - Defining systems expertise: effective simulation at the organizational level-
      implications for patient safety, disaster surge capacity, and facilitating the
      systems interface.
AB  - The Institute of Medicine's report "To Err is Human" identified simulation as a
      means to enhance safety in the medical field, just as flight simulation is used
      to improve the aviation industry. Yet, while there is evidence that simulation
      may improve task performance, there is little evidence that simulation actually
      improves patient outcome. Similarly, simulation is currently used to model
      teamwork-communication skills for disaster management and critical events, but
      little research or evidence exists to show that simulation improves disaster
      response or facilitates intersystem or interagency communication. Simulation
      ranges from the use of standardized patient encounters to robot-mannequins to
      computerized virtual environments. As such, the field of simulation covers a
      broad range of interactions, from patient-physician encounters to that of the
      interfaces between larger systems and agencies. As part of the 2008 Academic
      Emergency Medicine Consensus Conference on the Science of Simulation, our group
      sought to identify key research questions that would inform our understanding of
      simulation's impact at the organizational level. We combined an online discussion
      group of emergency physicians, an extensive review of the literature, and a
      "public hearing" of the questions at the Consensus Conference to establish
      recommendations. The authors identified the following six research questions: 1)
      what objective methods and measures may be used to demonstrate that simulator
      training actually improves patient safety? 2) How can we effectively feedback
      information from error reporting systems into simulation training and thereby
      improve patient safety? 3) How can simulator training be used to identify
      disaster risk and improve disaster response? 4) How can simulation be used to
      assess and enhance hospital surge capacity? 5) What methods and outcome measures
      should be used to demonstrate that teamwork simulation training improves disaster
      response? and 6) How can the interface of systems be simulated? We believe that
      exploring these key research questions will improve our understanding of how
      simulation affects patient safety, disaster surge capacity, and intersystem and
      interagency communication.

PMID- 18717651
TI  - Simulation in a disaster drill: comparison of high-fidelity simulators versus
      trained actors.
AB  - OBJECTIVES: High-fidelity patient simulation provides lifelike medical scenarios
      with real-time stressors. Mass casualty drills must construct a realistic
      incident in which providers care for multiple injured patients while
      simultaneously coping with numerous stressors designed to tax an institution's
      resources. This study compared the value of high-fidelity simulated patients with
      live actor-patients. METHODS: A prospective cohort study was conducted during two
      mass casualty drills in December 2006 and March 2007. The providers' completion
      of critical actions was tested in live actor-patients and simulators. A posttest
      survey compared the participants' perception of "reality" between the simulators
      and live actor victims. RESULTS: The victims (n = 130) of the mass casualty drill
      all had burn-, blast-, or inhalation-related injuries. The participants consisted
      of physicians, residents, medical students, clerks, and paramedics. The authors
      compared the team's execution of the 136 critical actions (17 critical actions x
      8 scenarios) between the simulators and the live actor-patients. Only one
      critical action was missed in the simulator group and one in the live actor
      group, resulting in a miss rate of 0.74% (95% confidence interval [CI] = 0.01% to
      4.5%). All questionnaires were returned and analyzed. The vast majority of
      participants disagreed or strongly disagreed that the simulators were a
      distraction from the disaster drill. More than 96% agreed or strongly agreed that
      they would recommend the simulator as a training tool. The mean survey scores for
      all participants demonstrated agreement that the simulators closely mimicked real
      life scenarios, accurately represented disease states, and heightened the realism
      of patient assessment and treatment options during the drill with the exception
      of nurse participants, who agreed slightly less strongly. CONCLUSIONS: This study
      demonstrated that simulators compared to live actor-patients have equivalent
      results in prompting critical actions in mass casualty drills and increase the
      perceived reality of such exercises.

PMID- 18717652
TI  - National growth in simulation training within emergency medicine residency
      programs, 2003-2008.
AB  - OBJECTIVES: The use of medical simulation has grown dramatically over the past
      decade, yet national data on the prevalence and growth of use among individual
      specialty training programs are lacking. The objectives of this study were to
      describe the current role of simulation training in emergency medicine (EM)
      residency programs and to quantify growth in use of the technology over the past
      5 years. METHODS: In follow-up of a 2006 study (2003 data), the authors
      distributed an updated survey to program directors (PDs) of all 179 EM residency
      programs operating in early 2008 (140 Accreditation Council on Graduate Medical
      Education [ACGME]-approved allopathic programs and 39 American Osteopathic
      Association [AOA]-accredited osteopathic programs). The brief survey borrowed
      from the prior instrument, was edited and revised, and then distributed at a
      national PDs meeting. Subsequent follow-up was conducted by e-mail and telephone.
      The survey concentrated on technology-enhanced simulation modalities beyond
      routine static trainers or standardized patient-actors (high-fidelity mannequin
      simulation, part-task/procedural simulation, and dynamic screen-based
      simulation). RESULTS: A total of 134 EM residency programs completed the updated
      survey, yielding an overall response rate of 75%. A total of 122 (91%) use some
      form of simulation in their residency training. One-hundred fourteen (85%)
      specifically use mannequin-simulators, compared to 33 (29%) in 2003 (p < 0.001).
      Mannequin-simulators are now owned by 58 (43%) of the programs, whereas only 9
      (8%) had primary responsibility for such equipment in 2003 (p < 0.001). Fifty
      eight (43%) of the programs reported that annual resident simulation use now
      averages more than 10 hours per year. CONCLUSIONS: Use of medical simulation has
      grown significantly in EM residency programs in the past 5 years and is now
      widespread among training programs across the country.

PMID- 18717653
TI  - Multiple effects of bevacizumab in angiogenesis: implications for its use in age
      related macular degeneration.
AB  - PURPOSE: This study aimed to elucidate the precise effects of bevacizumab in all
      steps in the neovascularization process in endothelial cells. METHODS: Human
      umbilical vein endothelial cells (HUVECs) were incubated with bevacizumab at
      concentrations within the clinically established range or with identical amounts
      of excipient. Cell cytotoxicity (evaluated by MTT assay), proliferation (by BrdU
      incorporation assay), apoptosis (by TUNEL assay), migration (by double-chamber
      assay) and vessel assembly in matrigel-coated plates were assessed in vitro.
      Mouse plug matrigel assays were performed to confirm in vitro results. RESULTS:
      Incubation of HUVECs with bevacizumab did not present cytotoxicity.
      Concentrations comparable with those after intravitreal doses of bevacizumab
      significantly reduced proliferation and migration capacity, and increased
      apoptotic rates in these cells. In addition, bevacizumab led to a significant
      decrease in the assembly of capillary-like structures on matrigel assay in
      comparison with excipient-treated cells. Further substantiating these in vitro
      findings, bevacizumab also inhibited angiogenesis in a mouse plug matrigel assay,
      as evaluated by haemoglobin content levels. CONCLUSIONS: These results
      demonstrate that clinical doses of bevacizumab are able to prevent several steps
      of the angiogenic process. Bevacizumab is thus currently recommended for treating
      disorders that present augmented angiogenesis.

PMID- 18717654
TI  - Unchanged heart rate-respiratory frequency ratio in preterm infants during
      spontaneous arousals.
AB  - AIM: To find out whether a correlation of heart rate (HR) and respiratory
      frequency (RF) defined as HR-RF-ratio (HRR) may be helpful to identify arousals
      in term and preterm infants. METHODS: Polygraphic recordings were performed in 25
      term infants (gestational age 40.1 +/- 1.1 weeks) and 25 preterm infants
      (gestational age 31.1 +/- 1.3 weeks) during undisturbed daytime sleep. Arousals
      were scored as suggested by the 'International Paediatric Work Group on Arousals'
      and divided into cortical arousals and subcortical arousals. HRR was defined as
      HR over RF. Arousals were compared to a 30-sec period preceding an arousals.
      RESULTS: Two hundred arousals were scored (100 cortical arousals and 100
      subcortical arousals). HRR increased during arousals in term infants (p < 0.001).
      This was true for cortical arousals (p < 0.001) and subcortical arousals (p <
      0.05) of term infants. In contrast, in preterm infants HRR remained unchanged
      during cortical arousals and subcortical arousals. CONCLUSION: An increase of HRR
      during arousals is a simple parameter to identify arousals in term infants, but
      not in preterm infants suggesting that an unchanged HRR might be an indicator of
      an immature arousal response.

PMID- 18717655
TI  - The cost of alcohol in California.
AB  - BACKGROUND: California is the largest alcohol market in the United States. In
      2005 alone, Californians consumed almost 14 billion alcoholic drinks, which
      contributed to many severe and potentially fatal alcohol-related illnesses and
      conditions. Alcohol use also causes violent and nonviolent crimes, as well as
      injuries and traffic collisions. While several studies have estimated the
      magnitude and cost of these problems nationally and others have analyzed underage
      drinking costs, no overall cost estimate at the state level currently exists for
      California. We present the first comprehensive estimate of the cost of alcohol
      consumption in California. METHODS: For each category of alcohol-related
      problems, we estimated fatal and nonfatal cases attributable to alcohol use. We
      multiplied alcohol-attributable cases by estimated costs per case to obtain total
      costs for each problem. Our estimates are presented in 2 sections, the economic
      costs, estimated using a human capital approach, and quality-of-life costs
      estimated using a quality adjusted life year framework. RESULTS: Alcohol
      consumption in California led to an estimated 9,439 deaths and 921,929 alcohol
      related problems, such as crime and injury in 2005. The economic cost of these
      problems is estimated at between $35.4 billion and $42.2 billion. Our main
      estimate is $38.5 billion, of which $5.4 billion was for medical and mental
      health spending, $25.3 billion in work losses, and $7.8 billion in criminal
      justice spending, property damage and public program costs. In addition, alcohol
      is responsible for severe reductions in individuals' quality of life in
      California. We estimate that the disability caused by injury, the personal
      anguish of violent crime victims, and the life years lost to fatality are the
      largest costs imposed by alcohol. The total value for this reduced quality of
      life in California is between $30.3 billion and $60.0 billion. Our main estimate
      for quality-of-life costs is $48.8 billion. CONCLUSIONS: In light of the
      associated substantial illness, injuries, death, and high cost to society,
      alcohol consumption in California needs serious attention. In addition, the
      methods developed in this paper can be expanded to estimate the cost of alcohol
      in other states.

PMID- 18717657
TI  - Safety and complications of percutaneous tracheostomy in a cohort of 800 mixed
      ICU patients.
AB  - Percutaneous tracheostomy is used primarily to assist weaning from mechanical
      ventilation in the intensive care unit. We report our experiences of 800 such
      procedures performed in the intensive care unit by a collaborative team (critical
      care and ENT specialists). Most procedures (85.6%) were performed by residents
      supervised by the intensive care unit staff. Complications occurred in 32
      patients (4%). Intraprocedural complications occurred in 17 patients (2.1%),
      early postprocedural complications in six (0.75%), and late postprocedural
      complications in nine (1.1%). No deaths were directly related to percutaneous
      tracheostomy. The incidence of complications was greater in percutaneous
      tracheostomy performed by the residents during their initial five attempts
      compared to their later attempts (9.2% vs 2.6%, p < 0.05). The low incidence of
      complications indicates that bedside percutaneous tracheostomy can be performed
      safely as a routine procedure in daily care of intensive care unit patients.

PMID- 18717658
TI  - Elective intra-aortic balloon counterpulsation during a high risk liver
      resection.
AB  - SUMMARY: We present the case of a 65-year-old male with severe coronary artery
      disease and a single colorectal liver metastasis. An elective intra-aortic
      balloon pump (IABP) was inserted following induction of anaesthesia to reduce
      left ventricular workload during his liver resection. After an uneventful
      recovery he was discharged on day 5. We review the literature on the elective use
      of these devices in cardiac surgery in which it is becoming routine practice in
      high risk patients. However in non-cardiac surgery there have been only 15
      published cases all in very high risk patients, with favourable outcomes. To our
      knowledge this is the first published case of the use of elective IABP during
      liver surgery.

PMID- 18717656
TI  - Ethanol-mediated DNA damage and PARP-1 apoptotic responses in cultured fetal
      cortical neurons.
AB  - BACKGROUND: Prior studies by many laboratories have illustrated that ethanol can
      elicit a cascade of caspase-dependent apoptotic events in cultured neurons.
      Studies in our laboratory have connected this to oxidative stress and effects on
      fetal cortical neuron glutathione homeostasis. AIMS: The intent of the following
      studies is to address mechanisms underlying ethanol-associated DNA damage that
      may be connected to apoptotic death of neurons. METHODS: Cultures of fetal rat
      cerebral cortical neurons were utilized. Estimates of DNA damage was determined
      by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining
      and nuclear condensation; Poly(ADP-ribose) polymerase-1 (PARP-1) expression was
      determined by immunostaining and Western blotting; and occurrence of parylation
      and AIF translocations were assessed by Western blotting. RESULTS: Ethanol
      treatment of the neurons generated increases in DNA damage by 4 hours while
      nuclear condensation was low at the short exposure period but increased markedly
      by 24 hours. This was temporally related to a marked up-regulation of PARP-1
      expression. Activity of PARP-1, as assessed by PolyADP-ribose (PAR) formation,
      occurred within 15 minutes and peaked by 6 to 8 hours of ethanol treatment. An
      almost complete translocation of apoptosis inducing factor (AIF) from
      mitochondria to the nucleus occurred by 24 hours of ethanol treatment (4.0
      mg/ml). Ethanol treatment for 4, 12, and 24 hours elicited an increasing caspase
      mediated cleavage of PARP-1 to its 24 kDa fragment. CONCLUSIONS: These data
      illustrate the rapid occurrence of DNA damage following ethanol exposure and that
      PARP-1 pathways may play a role in the subsequent apoptotic death of these
      neurons.

PMID- 18717659
TI  - Posterior reversible encephalopathy syndrome: a report of a case with atypical
      features.
AB  - We report a case of a young woman presenting with profound depression of
      consciousness and intra-uterine death in the late stages of an unbooked
      pregnancy. She proceeded to develop features of cardiovascular, renal, hepatic
      and haematological failures. The patient was challenging to manage in view of
      uncertainty regarding the underlying cause, and required multidisciplinary
      consultation. A diagnosis was subsequently made of posterior reversible
      encephalopathy syndrome in the context of pre-eclampsia. We review the typical
      presentation and wide-ranging associations of this recently described clinico
      neuroradiological syndrome, and look at how appropriate management may lead to
      rapid resolution of its often life-threatening features. We highlight the
      importance to anaesthetists and critical care physicians of recognising even
      atypical cases such as this one in view of key differences in management from
      similarly presenting conditions.

PMID- 18717660
TI  - Multiple organ failure and severe bone marrow dysfunction in two 18 year-old
      Caucasian patients: Epstein-Barr virus and the haemophagocytic syndrome.
AB  - Haemophagocytic lymphohistiocytosis secondary to viral infection is an unusual
      but well recognised cause of bone marrow dysfunction and multiple organ failure
      in young patients. Two 18 year-old patients were admitted to a tertiary liver
      unit with features of acute liver failure, cardio-respiratory collapse and
      pancytopenia. Serological tests and bone marrow examination with in-situ
      hybridisation revealed severe acquired haemophagocytic lymphohistiocytosis
      secondary to acute Epstein-Barr virus infection. Both patients died despite full
      supportive therapy; the first due to pulmonary haemorrhage, the second due to
      acute respiratory distress syndrome refractory to high frequency oscillatory
      ventilation. The clinical spectrum, diagnostic features and current evidence
      based recommendations for treatment of this condition are explored. The diagnosis
      of haemophagocytic lymphohistiocytosis should be considered in young patients
      with marked bone marrow dysfunction and multiple organ failure. Further research
      into appropriate therapy for patients with acute severe forms of the disease who
      require intensive organ support is required.

PMID- 18717661
TI  - Clinical experience with a pumpless extracorporeal lung assist device.
AB  - We present three patients with respiratory failure in whom conventional
      mechanical lung ventilation resulted in unacceptably high levels of carbon
      dioxide, severe acidosis and high vasopressor requirements. A pumpless
      arteriovenous extracorporeal carbon dioxide removal device (Novalung) was
      inserted. Arterial carbon dioxide levels were reduced rapidly with a
      corresponding increase in pH, reduction in vasopressor requirements and reduction
      in inspiratory pressures. One patient required the additional use of high
      frequency oscillatory ventilation. There were no complications associated with
      use of the device. We conclude that use of extracorporeal carbon dioxide removal
      devices should be considered at an early stage in the management of respiratory
      failure refractory to conventional ventilatory techniques.

PMID- 18717662
TI  - The effect of temperature on bougies: a photographic and manikin study.
AB  - We investigated the effect of temperature on single use and reuseable bougies. In
      a photographic study, three bougies (Portex Venn reuseable (R), Portex single use
      (S) and Breathesafe single use (B)) were exposed to increasing temperatures and
      sequential photographs were taken of the bougies uncoiling from a preformed
      curve. Bougie type was associated with rate of uncoiling, type R maintaining its
      curve the longest but changing temperature did not affect this. In a randomised
      cross-over manikin study, 16 anaesthetists attempted to pass two bougies (Portex
      reuseable (R) and Portex single use (S)) at three temperatures (10, 20 and 30
      degrees C) into the trachea of a manikin. Type R was significantly associated
      with higher success rate of tracheal placement compared to type S. Change of
      temperature was significant with success rate increasing with lower temperature.
      The odds of success at 10 degrees C was six times that at 30 degrees C (OR (95%)
      6.7 (1.7, 25.7)). We concluded that both bougies performed best at 10 degrees C.

PMID- 18717663
TI  - Evaluation of bag-valve-mask ventilation in simulated toxic environments.
AB  - Bag-valve-mask ventilation is a key component of life support, but only one
      handheld resuscitator is designed to operate in contaminated or toxic
      atmospheres. Following Institutional Review Board approval we determined the
      efficacy of this device. Twenty anaesthetists ventilated a modified manikin,
      either with or without a combination filter attached to the resuscitator inlet.
      The mean (SD) maximum minute volume achieved without the filter was 9.3 (3.1) l x
      min(-1). Use of the inlet filtration system reduced the maximum minute volume
      significantly to 6.4 (2.2) l x min(-1) (reduction of 30%, p = 0.0017). The
      achieved maximum minute volumes ranged from 13.4 to 4 l x min(-1) in the controls
      and from 9.5 to 3 l x min(-1) in the filter group. The delay in refilling of the
      self-inflatable bag may have resulted in reduced achievable minute volumes. The
      range of the maximum minute volumes in both groups highlights the need for
      continuous bag-valve-mask ventilator training.

PMID- 18717664
TI  - The Heidelberg Peri-anaesthetic Questionnaire--development of a new refined
      psychometric questionnaire.
AB  - We have developed a questionnaire to assess patients' peri-anaesthetic
      satisfaction. We recruited 1398 patients and 59 health care professionals for
      construction and validation. Relevant items were rated for preferences. The
      resulting questions underwent a cognitive and a standard pretest. The resultant
      Heidelberg Peri-anaesthetic Questionnaire consists of 38 questions about five
      identified themes: trust and atmosphere; fear; discomfort; treatment by
      personnel; and information and waiting. Internal consistency was demonstrated for
      the sum score (Cronbach's alpha = 0.79) and the five factors (Cronbach's alpha =
      0.42-0.79). Multivariate analysis found significant influences of age, school
      education, marital status and duration of anaesthesia. Dissatisfied patients had
      a median (IQR [range]) of 73% (66-76% [35-83]), and satisfied patients 92% (90
      94% [88-100]) of the sum score. The Heidelberg Peri-anaesthetic Questionnaire
      offers a valid and reliable way to identify dissatisfied patients and generate
      quality improvement and also has use as a benchmark tool.

PMID- 18717665
TI  - Effects of target concentration infusion of propofol and tracheal intubation on
      QTc interval.
AB  - This study was designed to evaluate the effect of target controlled infusion of
      propofol on QTc interval and tracheal intubation. Twenty-five unpremedicated, ASA
      class I or II patients were selected and target concentration infusion of
      propofol at 5 microg x ml(-1) was used throughout the study. The QTc interval was
      measured before anaesthetic induction (baseline, T1), 10 min after propofol
      infusion (T2), immediately after tracheal intubation (T3), and 1 min after
      tracheal intubation (T4). The QTc interval increased significantly at 10 min
      after the propofol infusion started compared to baseline (p = 0.003). After
      tracheal intubation, the QTc interval was further increased when compared to that
      at T2 (p < 0.0001). The increased QTc interval was within normal limit and no
      patient had an arrhythmia. In conclusion, although statistically significant, the
      increase in QTc interval was too small to be clinically significant during
      propofol infusion. However, the combination of propofol and tracheal intubation
      must be used carefully in patients with prolonged QTc interval.

PMID- 18717666
TI  - Association among growth, food consumption-related traits and amylase gene
      polymorphism in the Pacific oyster Crassostrea gigas.
AB  - To examine further a previously reported association between amylase gene
      polymorphism and growth in the Pacific oyster Crassostrea gigas, ecophysiological
      parameters and biochemical and molecular expression levels of alpha-amylase were
      studied in Pacific oysters of different amylase genotypes. Genotypes that
      previously displayed significantly different growth were found to be
      significantly different for ingestion and absorption efficiency. These estimated
      parameters, used in a dynamic energy budget model, showed that observed ingestion
      rates (unlike absorption efficiencies) allowed an accurate prediction of growth
      potential in these genotypes. The observed association between growth and amylase
      gene polymorphism is therefore more likely to be related to ingestion than to
      absorption efficiency. Additionally, relative mRNA levels of the two amylase
      cDNAs were also strongly associated with amylase gene polymorphism, possibly
      reflecting variation in an undefined regulatory region, although no corresponding
      variation was observed in specific amylase activity. Amylase gene sequences were
      determined for each genotype, showing the existence of only synonymous or
      functionally equivalent non-synonymous polymorphisms. The observed associations
      among growth, food consumption-related traits and amylase gene polymorphism are
      therefore more likely to be related to variation in the level of amylase gene
      expression than to functional enzymatic variants.

PMID- 18717667
TI  - Linkage disequilibrium and signatures of selection on chromosomes 19 and 29 in
      beef and dairy cattle.
AB  - The objective of this study was to quantify the extent of linkage disequilibrium
      (LD) on bovine chromosomes 19 and 29 and to study the pattern of selection
      signatures in beef and dairy breeds (Angus and Holstein) of Bos taurus. The
      extent of LD was estimated for 370 and 186 single nucleotide polymorphism markers
      on BTA19 and 29 respectively using the square of the correlation coefficient
      (r(2)) among alleles at pairs of loci. A comparison of the extent of LD found
      that the decline of LD followed a similar pattern in both breeds. We observed
      long-range LD and found that LD dissipates to background levels at a locus
      separation of about 20 Mb on both chromosomes. Along each chromosome, patterns of
      LD were variable in both breeds. We find that a minimum of 30 000 informative and
      evenly spaced markers would be required for whole-genome association studies in
      cattle. In addition, we have identified chromosomal regions that show some
      evidence of selection for economically important traits in Angus and Holstein
      cattle. The results of this study are of importance for the design and
      application of association studies.

PMID- 18717668
TI  - Investigating the genetic basis of pork tenderness: genomic analysis of porcine
      CAST.
AB  - A quantitative trait locus (QTL) affecting pork tenderness was recently detected
      within the Illinois Meat Quality Pedigree (IMQP) and fine-mapped to the region of
      porcine chromosome 2 (SSC2) harbouring the functional candidate gene calpastatin
      (CAST). To identify molecular variation that may underlie the observed
      differences in tenderness phenotypes, we characterized the porcine CAST gene and
      analysed allelic variation within the F(1) boars of the IMQP. The complete
      genomic sequence of porcine CAST has been determined, and was found to contain 35
      exons spanning nearly 123 kb. Using the rapid amplification of cDNA ends (RACE)
      method, calpastatin transcript types I-III, as well as a putative novel
      transcript type, were detected within porcine skeletal muscle. Variability in
      transcription initiation and termination sites was observed, and alternative
      splicing of exons 1y and 3 was evident. Nearly 77.6% of the CAST gene, including
      all exons, was re-sequenced from each of six IMQP F(1) boars, and almost 900
      polymorphisms were identified. The heterozygosity of nearly 400 polymorphisms
      appeared to be concordant with the previous QTL data, and the location of this
      variation within the CAST gene suggests that a causative mutation is likely to be
      regulatory. Functional characterization of CAST variation should enhance
      understanding of the molecular basis of pork tenderness, and thus allow for
      genetic improvement of pork products. The effectiveness of CAST polymorphisms for
      marker-assisted selection of pork tenderness can now be assessed.

PMID- 18717669
TI  - Use of nicotine replacement therapy during pregnancy and stillbirth: a cohort
      study.
AB  - OBJECTIVE: The objective of this study was to examine whether the use of nicotine
      replacement therapy (NRT) during pregnancy increases the risk of stillbirth.
      DESIGN: Cohort study with prospective data. SETTING: Denmark 1996-2002.
      POPULATION: A total of 87,032 singleton pregnancies enrolled in the Danish
      National Birth Cohort for which information on NRT use as well as smoking was
      available. METHODS: Outcome of pregnancy was identified by register linkage, with
      <1% loss to follow up. We conducted Cox regression analyses to estimate the
      hazard ratio (HR) and 95% CI of stillbirth according to the use of NRT, type of
      NRT use and a combination of NRT use and smoking. MAIN OUTCOME MEASURES:
      Stillbirth, defined as delivery of a dead fetus after 20 completed weeks of
      gestation. RESULTS: A total of 495 pregnancies (5.7 in 1000 births) ended in
      stillbirth, 8 of which were among NRT users (4.2 in 1000 births). After
      adjustment for confounders, women who used NRT during pregnancy had a HR of 0.57
      (95% CI 0.28-1.16) for stillbirth compared with those who did not use NRT.
      Smoking during pregnancy was associated with an increased risk of stillbirth (HR
      1.46, 95% CI 1.17-1.82), while women who both smoked and used NRT had a HR of
      0.83 (95% CI 0.34-2.00) compared with nonsmoking women who did not use NRT.
      CONCLUSION: Our study does not indicate that use of NRT during pregnancy
      increases the risk of stillbirth.

PMID- 18717670
TI  - Outcomes for patients with pT0 disease after radical nephroureterectomy for upper
      tract urothelial carcinoma.

PMID- 18717671
TI  - Vitamin D protects keratinocytes from deleterious effects of ionizing radiation.
AB  - BACKGROUND: Radiotherapy can induce severe skin responses that may limit the
      clinically acceptable radiation dose. The responses include erythema, dry and
      moist desquamation, erosions and dermal-epidermal blister formation. These
      effects reflect injury to, and reproductive failure of, epidermal cells and may
      also be due to dysregulation of the tissue remodelling process caused by
      excessive proteolytic activity. Calcitriol, the hormonally active vitamin D
      metabolite, protects keratinocytes from programmed cell death induced by various
      noxious stimuli. OBJECTIVE: To examine whether calcitriol protects proliferating
      keratinocytes from the damage inflicted by ionizing radiation under conditions
      similar to those employed during radiotherapy. METHODS: Autonomously
      proliferating HaCaT keratinocytes, used as a model for basal layer keratinocytes,
      were irradiated using a linear accelerator. Cell death was monitored by vital
      staining, executioner caspase activation, lactic dehydrogenase release and colony
      formation assay. Induction of matrix metalloproteinase-9 was assessed by
      gelatinase activity assay and mRNA determination. Levels of specific proteins
      were determined by immunoblotting. RESULTS: Treatment with calcitriol inhibited
      both caspase-dependent and -independent programmed cell death occurring within 48
      h of irradiation and increased the colony formation capacity of irradiated cells.
      These effects may be attributable to inhibition of the c-Jun NH(2)-terminal
      kinase cascade and to upregulation of the truncated antiapoptotic isoform of p63.
      Treatment with the hormone also attenuated radiation-induced increase in matrix
      metalloproteinase-9 protein and mRNA levels. CONCLUSIONS: The results of this
      study suggest that active vitamin D derivatives may attenuate cell death and
      excessive proteolytic activity in the epidermis due to exposure to ionizing
      radiation in the course of radiotherapy.

PMID- 18717672
TI  - A novel GJB6 missense mutation in hidrotic ectodermal dysplasia 2 (Clouston
      syndrome) broadens its genotypic basis.

PMID- 18717673
TI  - Bioavailability of aminolaevulinic acid and methylaminolaevulinate in basal cell
      carcinomas: a perfusion study using microdialysis in vivo.
AB  - BACKGROUND: Photodynamic therapy is becoming a popular treatment for superficial
      nonmelanoma precancerous and cancerous lesions, showing excellent cosmetic
      results. Nevertheless, the reported cure rates vary and the transdermal
      penetration of drugs has been discussed as a limiting factor, particularly for
      treatment of nodular basal cell carcinoma (BCC). OBJECTIVES: To investigate the
      transdermal penetration of aminolaevulinic acid (ALA) and methylaminolaevulinate
      (MAL) in BCC in vivo using a microdialysis technique. The different prodrugs were
      compared and the effect of curettage was studied. METHODS: Twenty patients with
      27 histologically verified BCCs (13 superficial, 14 nodular) were included. All
      lesions were located at the front of the body (head and face excluded). The first
      10 patients included were treated with MAL (13 BCCs), and the following 10
      patients with ALA (14 BCCs). A light curettage was performed on every second
      lesion (curettage, n = 13; noncurettage, n = 14). Microdialysis catheters were
      inserted into the tumours at tissue depths varying from 0.4 to 1.9 mm. Dialysates
      were collected at 15-30-min intervals for 4 h and the interstitial concentrations
      of MAL and ALA were determined using high-performance liquid chromatography.
      RESULTS: No significant difference in interstitial drug concentration was
      observed between lesions treated with ALA or MAL during the 4-h measurement
      period. However, for the lesions with deeper catheter locations, i.e. at or below
      1 mm (n = 11), drug concentrations above the detection limit were obtained in
      only six lesions. All but one BCC with superficial catheter location, i.e. < 1 mm
      (n = 16), exhibited detectable drug concentration (P = 0.026). The interstitial
      peak concentrations were reached within 90 min in 23 of the 27 BCCs, but were not
      found to be correlated with the depth of the catheters. No difference was found
      when comparing superficial and nodular BCCs, and the effect of curettage was
      found to be negligible. CONCLUSIONS: The results imply that there is no
      significant difference in transdermal penetration of ALA and MAL in tumour
      tissue. Detectable levels of drug were not obtained in almost 50% of the lesions
      where catheters were situated 1-1.9 mm in the lesion. Curettage was not found to
      affect the interstitial concentration, indicating that penetration of drug indeed
      might be a problem when treating BCCs thicker than 1 mm.

PMID- 18717674
TI  - Infantile-onset cutaneous T-cell lymphoma.
AB  - BACKGROUND: Mycosis fungoides (MF), the most common form of cutaneous T-cell
      lymphoma (CTCL), is mainly a disease of the elderly. OBJECTIVES: To review
      paediatric CTCL cases reported in the literature, with a focus on the time
      between onset of symptoms and establishment of a correct diagnosis. METHODS: A
      review of the literature was carried out and a case reported. RESULTS: A total of
      254 cases of CTCL have been reported in children aged<16 years, 13 cases (<1% of
      all reported cases) in children below the age of 2 years, and only seven cases
      (including ours) during the first year of life. CTCL was most prevalent in
      children aged 10-12 years. The delay between age of onset and establishment of
      diagnosis was largest in the youngest age group (0-3 years), and declined
      steadily thereafter, thus reflecting the increasing likelihood that CTCL is
      considered in the differential diagnosis of skin disorders with increasing age of
      the patient. CONCLUSIONS: The diagnosis of CTCL is frequently delayed in young
      children. It needs to be considered in chronic 'eczematous' skin lesions
      irrespective of the patient's age, and including infants.

PMID- 18717675
TI  - Randomized controlled trial comparing the effectiveness of 308-nm excimer laser
      alone or in combination with topical hydrocortisone 17-butyrate cream in the
      treatment of vitiligo of the face and neck.
AB  - BACKGROUND: Vitiligo is a pigmentary disorder which may have disfiguring
      consequences. Its treatment remains a challenge. OBJECTIVES: We designed a
      parallel-group randomized controlled trial to compare the effectiveness of 308-nm
      excimer laser alone or in combination with topical hydrocortisone 17-butyrate
      cream in patients with vitiligo unresponsive to previous treatment with topical
      steroids or narrow-band ultraviolet (UV) B phototherapy. METHODS: Consecutive
      patients aged 18-75 years with nonsegmental vitiligo localized on the face and/or
      neck lacking response to previous conventional treatment were eligible. In total,
      84 patients (44 women and 40 men, mean age 44 years) were randomized to 308-nm
      excimer laser phototherapy twice weekly alone or in combination with topical
      hydrocortisone 17-butyrate cream twice daily for three periods of 3 weeks
      followed by a 1-week steroid-free interval. The primary outcome was a reduction
      of at least 75% of the overall lesional areas as judged by automatic image
      analysis on reflected UV photographs, conducted blind to treatment assignment, at
      12 weeks compared with baseline. Secondary outcomes were clearance, and
      improvements on Physician's Global Assessment (PGA) and Skindex-29 scores.
      RESULTS: A total of 76 (90%) patients completed the study. In an intention-to
      treat analysis, seven [16.6%; 95% confidence interval (CI) 5.3-27.8%] patients in
      the excimer monotherapy arm and 18 (42.8%; 95% CI 27.8-57.8%) in the combination
      arm showed > or = 75% reduction of vitiligo lesions at 12 weeks (chi(2) test
      6.89, P = 0.0087). Clearance was observed in two (4.7%; 95% CI 1.6-11.2%) and
      nine (21.4%; 95% CI 9.0-33.8%) patients, respectively (Fisher's exact test P =
      0.04). A significant difference also emerged for PGA scores, while no difference
      was documented for Skindex-29. CONCLUSIONS: Recalcitrant vitiligo of the face and
      neck may benefit from the combination of excimer laser phototherapy with topical
      hydrocortisone 17-butyrate cream.

PMID- 18717676
TI  - Indeterminate results on the interferon-gamma release assay for tuberculosis
      screening should not be ignored.

PMID- 18717677
TI  - Xeroderma pigmentosum group C in a French Caucasian patient with multiple
      melanoma and unusual long-term survival.
AB  - We report the case of an 83-year-old French woman with multiple melanomas showing
      a severe DNA repair deficiency, corrected after transfection by XPC cDNA. Two
      biallelic mutations in the XPC gene are reported: an inactivating frameshift
      mutation in exon 15 (c.2544delG, p.W848X) and a missense mutation in exon 11
      (c.2108 C>T, P703L). We demonstrate that these new mutations are involved in the
      DNA repair deficiency and confirm the diagnosis of xeroderma pigmentosum from
      complementation group C (XP-C). We speculate that the coexistence of a MC1R
      variant may be involved in the phenotype of multiple melanomas and that the
      unusual long-term survival may be related to a lower ultraviolet radiation
      exposure and to a regular clinical follow-up. This patient appears to be the
      first French Caucasian XP-C case and one of the oldest living patients with XP
      reported worldwide.

PMID- 18717679
TI  - Impact of childhood vitiligo on adult life.
AB  - BACKGROUND: The onset of vitiligo occurs before the age of 20 years in 50% of
      patients. Having a chronic disease in childhood can impede a child's health
      related quality of life (HRQL). OBJECTIVES: Firstly, to compare the social and
      psychosexual development and current HRQL of young adult patients with childhood
      vitiligo with those of a group of healthy controls. Secondly, to compare these
      outcomes in patients reporting negative childhood experiences with those of
      patients not reporting negative childhood experiences. METHODS: Eligible patients
      were mailed questionnaires on (i) sociodemographic and clinical characteristics,
      (ii) social and psychosexual development, (iii) generic and dermatology-specific
      HRQL, (iv) presence of negative childhood experiences related to vitiligo, (v)
      specification of these negative experiences and (vi) patients' recommendations
      for further care. RESULTS: A total of 232 patients with vitiligo completed the
      questionnaires. Social and psychosexual development and generic HRQL in young
      adult patients with childhood vitiligo were not different from those of healthy
      controls. However, patients reporting negative childhood experiences reported
      significantly more problems in social development than those not reporting
      negative experiences. Furthermore, negative childhood experiences were
      significantly associated with more HRQL impairment in early adulthood.
      CONCLUSIONS: Reporting negative experiences from childhood vitiligo appears to be
      associated with HRQL impairment in young adults with vitiligo.

PMID- 18717678
TI  - Hyperglycaemic conditions decrease cultured keratinocyte mobility: implications
      for impaired wound healing in patients with diabetes.
AB  - BACKGROUND: Elevated blood glucose in patients with diabetes mellitus (DM) leads
      to complications including poor wound healing. Proper keratinocyte migration and
      proliferation are the crucial steps during re-epithelialization. We hypothesize
      that the impaired wound healing in patients with DM is due to the disruption of
      proper re-epithelialization. OBJECTIVES: We aimed to explore the effects of high
      glucose on keratinocytes in terms of cell migration and proliferation. METHODS:
      Keratinocytes were cultivated in normal and high glucose conditions. Their
      viability was evaluated by MTS assay. Transwell migration and in vitro scratch
      assays were used to evaluate their mobility. The mRNA expressions and activities
      of matrix metalloproteinase (MMP)-2 and MMP-9 were determined. The mRNA of their
      respective physiological inhibitors, tissue inhibitor of MMP (TIMP)-1 and TIMP-2,
      was also evaluated. Immunofluorescent staining and Western blotting were used to
      examine the expression of phosphorylated focal adhesion kinase (pp125(FAK)). The
      impacts of high glucose on keratinocyte proliferation were assessed by 5-bromo-2'
      deoxyuridine incorporation assay. RESULTS: High glucose treatment did not affect
      keratinocyte viability up to 3 days. In contrast, the mobility of keratinocytes,
      the activities and gene expressions of MMP-2 and MMP-9, the expression of
      pp125(FAK), and the cell proliferation after 5 days were significantly
      downregulated after hyperglycaemic treatments while the mRNA expression of TIMP-1
      increased. CONCLUSIONS: Under hyperglycaemic conditions, keratinocytes
      demonstrate reduced migration and decreased proliferation capacities. These
      impairments of keratinocyte functions are likely to result in inadequate re
      epithelialization. These defective physiological events provide a reasonable
      explanation for the poor wound healing commonly observed in patients with DM.

PMID- 18717681
TI  - Comedication related to comorbidities: a study in 1203 hospitalized patients with
      severe psoriasis.
AB  - BACKGROUND: Psoriasis is a common dermatological disorder characterized by an
      immune-mediated chronic inflammation which is associated with a variety of other
      diseases commonly referred to as comorbidities. The treatments for these diseases
      may interfere with the course and the treatment of psoriasis. Little is known on
      the general drug intake of patients with psoriasis. OBJECTIVES: To gain more
      insight into the general drug intake of patients with severe psoriasis. A
      correlation of comedication to respective diseases could lead to a better
      knowledge of comorbidities. METHODS: Data on demographics, comedication and
      comorbidities from 1203 patients with severe psoriasis in Germany were analysed.
      As a control group data from 7099 subjects from the German National Health Survey
      1998 were used. RESULTS: Patients with severe psoriasis are receiving
      significantly more different systemic drugs on average than the general
      population, with the most prominent difference in multidrug treatment. Drugs used
      in the treatment of arterial hypertension, diabetes mellitus and other diseases
      of the metabolic syndrome as well as oral anticoagulants and anticonvulsant
      agents showed the greatest differences. Special characteristics of
      antihypertensive drug treatments could be determined. CONCLUSIONS: The data
      obtained in this study provide the basis for an improved management of patients
      with psoriasis. Knowledge of existing comedication and comorbidities may lead to
      the ability to treat psoriasis and comorbidities at the same time more safely and
      to use possible synergistic effects.

PMID- 18717682
TI  - Gene expression study of IL10 family genes in vitiligo skin biopsies, peripheral
      blood mononuclear cells and sera.
AB  - BACKGROUND: Vitiligo is a pigmentation disorder, the cause of which is complex
      and not yet fully understood. There is a significant change of epidermal
      cytokines in involved skin of patients with vitiligo compared with uninvolved
      skin and skin of healthy controls, thus suggesting a possible involvement of
      cytokines in the pathogenesis of vitiligo. OBJECTIVES: To evaluate potential
      roles of IL10 family cytokines (IL10, IL19, IL20, IL22 and IL24) in vitiligo.
      Along with the selected cytokines, we investigated subunits of the receptors
      (IL10RA, IL10RB, IL20RA and IL22RA1) which are involved in the signalling pathway
      of the cytokines. METHODS: Quantitative real-time polymerase chain reaction was
      used to detect mRNA expression levels in samples extracted from skin biopsies and
      peripheral blood mononuclear cells and an enzyme-linked immunosorbent assay was
      used to measure protein concentrations in serum from patients with vitiligo and
      healthy controls. RESULTS: IL22 is significantly associated with vitiligo,
      especially with the active stage of vitiligo, as shown by results of mRNA
      expression and supported by results of protein level in sera. IL22 may provoke
      inflammation which leads to destruction of melanocytes. CONCLUSIONS: The actual
      role of IL22 during pathogenesis of vitiligo remains to be better characterized.
      Signal transductions of other investigated cytokines seem to be regulated on the
      expression level of their receptor complex subunits.

PMID- 18717680
TI  - Fractionated 5-aminolaevulinic acid-photodynamic therapy vs. surgical excision in
      the treatment of nodular basal cell carcinoma: results of a randomized controlled
      trial.
AB  - BACKGROUND: Skin cancer incidence rates have been increasing for decades and this
      increase is expected to continue. Surgical excision (SE) is the treatment of
      first choice for nodular basal cell carcinoma (nBCC). Photodynamic therapy (PDT)
      has proven to be an effective treatment for superficial basal cell carcinoma. Its
      long-term efficacy in nBCC has not yet been established. OBJECTIVES:
      Prospectively compare the efficacy of 5-aminolaevulinic acid (ALA)-PDT and SE in
      terms of failure rates with long-term follow-up. Determinants of failure in the
      study population, such as the effect of tumour depth, were analysed
      retrospectively. METHODS: A randomized controlled trial in 173 primary nBCCs in
      149 patients. Primary nBCCs were randomly assigned either to PDT (n = 85) or to
      SE (n = 88). Tumours treated with PDT were illuminated twice on the same day, 4 h
      after application of ALA cream, 3 weeks after debulking. SE was performed under
      local anaesthesia with a 3-mm margin, followed by histological examination. An
      intention-to-treat analysis was performed. RESULTS: In total, 171 primary nBCCs
      in 149 patients were treated. A 3-year interim analysis revealed that the
      cumulative incidence of failure was 2.3% for SE and 30.3% for PDT (P < 0.001).
      Tumour depth and other analysed determinants of failure were not significantly
      related to treatment failure. CONCLUSIONS: SE proved to be significantly more
      effective than treatment with fractionated illumination ALA-PDT. Therefore, in
      the treatment of primary nBCC, SE is preferred over PDT following this treatment
      regimen.

PMID- 18717683
TI  - Activation of kinin B receptor triggers differentiation of cultured human
      keratinocytes.
AB  - BACKGROUND: Keratinocyte life span is modulated by receptors that control
      proliferation and differentiation, key processes during cutaneous tissue repair.
      The kinin B(1) receptor (B(1)R) has been reported in normal and pathological
      human skin, but so far there is no information about its role in keratinocyte
      biology. OBJECTIVES: To determine the consequence of kinin B(1)R stimulation on
      tyrosine phosphorylation, a key signalling mechanism involved in keratinocyte
      proliferation and differentiation. METHODS: Subconfluent primary cultures of
      human keratinocytes were used to investigate tyrosine phosphorylation, epidermal
      growth factor receptor (EGFR) transactivation, cell proliferation and
      keratinocyte differentiation. Cell proliferation was assessed by measuring
      bromodeoxyuridine incorporation whereas assessment of cell differentiation was
      based on the expression of filaggrin, cytokeratin 10 (CK10) and involucrin.
      RESULTS: The major proteins phosphorylated, after B(1)R stimulation, were of
      molecular mass 170, 125, 89 and 70 kDa. The 170- and 125-kDa proteins were
      identified as EGFR and p125(FAK), respectively. Phosphorylation was greatly
      reduced by GF109203X and by overexposure of keratinocytes to phorbol 12-myristate
      13-acetate, indicating the participation of protein kinase C. B(1)R stimulation
      did not increase [Ca(2+)]i, but triggered EGFR transactivation, an event that
      involved phosphorylation of Tyr(845), Tyr(992) and Tyr(1068) of EGFR. B(1)R
      stimulation did not elicit keratinocyte proliferation, but triggered cell
      differentiation, visualized as an increase of filaggrin, CK10 and involucrin.
      Blockade of EGFR tyrosine kinase by AG1478, before B(1)R stimulation, produced an
      additional increase in filaggrin expression. CONCLUSIONS: The kinin B(1)R may
      contribute to keratinocyte differentiation and migration by triggering specific
      tyrosine signalling pathways or by interacting with the ErbB receptor family.

PMID- 18717684
TI  - Deletions of BRCA1/2 and p53 R248W gain-of-function mutation suggest impaired
      homologous recombination repair in fragile histidine triad-negative sebaceous
      gland carcinomas.
AB  - BACKGROUND: Sebaceous gland carcinomas represent rare malignancies of the skin
      and some 60% of them demonstrate high-grade microsatellite instability on the
      background of a defective mismatch repair system. However, a significant fraction
      of periocular sebaceous gland carcinomas exhibits microsatellite stability
      associated with a frequent loss of the candidate tumour suppressor fragile
      histidine triad (FHIT). OBJECTIVES: We hypothesized that in those sebaceous gland
      carcinomas with microsatellite stability and loss of FHIT, effector molecules
      participating in homologous recombination repair (HRR), such as BRCA1/2, could be
      somatically inactivated. METHODS: A pilot series of 10 paraffin-embedded
      sebaceous gland carcinoma specimens with a defined FHIT status was studied for
      loss of heterozygosity (LOH) events in the genes BRCA1, BRCA2, FHIT and WWOX. We
      sequenced the coding exons 5-8 of the p53 gene. RESULTS: Sebaceous gland
      carcinomas with FHIT negativity displayed LOH and biallelic deletions of the
      BRCA1 gene in five of 10 (50%) of the sebaceous gland carcinoma specimens
      analysed. Tumour-specific genomic losses close to BRCA2 were also uncovered. A
      homozygous p53 R248W gain-of-function mutation as the result of a CGG to TGG
      transition was identified in one of seven sebaceous gland carcinomas. It has been
      demonstrated previously that p53 R248W mutants inactivate ATM-directed HRR. This
      particular sebaceous gland carcinoma presented with concomitant genomic deletions
      at the BRCA1 and BRCA2 loci, and also at the constitutively fragile sites
      FRA3B/FHIT and FRA16D/WWOX. CONCLUSIONS: Our study demonstrates for the first
      time that microsatellite-stable FHIT-negative sebaceous gland carcinomas
      accumulate mutations that target central components of the HRR network. This
      observation will prompt investigations in synthetic lethality of BRCA-deficient
      sebaceous gland carcinomas by therapeutic poly(ADP-ribose) polymerase inhibitors.

PMID- 18717685
TI  - Age-dependent risks in genetic counseling for spinocerebellar ataxia type 2.

PMID- 18717686
TI  - A 2.1 Mb deletion adjacent but distal to a 14q21q23 paracentric inversion in a
      family with spherocytosis and severe learning difficulties.
AB  - A familial q21.1q23.2-inversion on chromosome 14 that co-segregated with
      spherocytosis and learning difficulties or mild mental retardation was
      extensively investigated by bacterial artificial chromosome fluorescence in situ
      hybridization and array-comparative genomic hybridization. As expected, a
      deletion of the beta-spectrin gene SPTB, a known cause of spherocytosis, was
      found. More unexpectedly, this deletion was approximately 1.6 Mb distal to the
      14q23.2-inversion breakpoint. The deletion spanned approximately 2.1 Mb and
      contained 15 annotated genes in addition to SPTB, among them PLEKHG3, a guanide
      nucleotide exchange factor for Rho GTPases. This gene is highly expressed in the
      brain and our best candidate for causing the mild mental retardation. The case
      illustrates that inversions can be associated with microdeletions close to but
      not including one of the inversion breakpoints.

PMID- 18717687
TI  - Autistic features with speech delay in a girl with an approximately 1.5-Mb
      deletion in 6q16.1, including GPR63 and FUT9.

PMID- 18717688
TI  - Amphibian commerce as a likely source of pathogen pollution.
AB  - The commercial trade of wildlife occurs on a global scale. In addition to
      removing animals from their native populations, this trade may lead to the
      release and subsequent introduction of nonindigenous species and the pathogens
      they carry. Emerging infectious diseases, such as chytridiomycosis caused by the
      chytrid fungus Batrachochytrium dendrobatidis (Bd), and ranaviral disease have
      spread with global trade in amphibians and are linked to amphibian declines and
      die-offs worldwide, which suggests that the commercial trade in amphibians may be
      a source of pathogen pollution. We screened tiger salamanders involved in the
      bait trade in the western United States for both ranaviruses and Bd with
      polymerase chain reaction and used oral reports from bait shops and ranavirus DNA
      sequences from infected bait salamanders to determine how these animals and their
      pathogens are moved geographically by commerce. In addition, we conducted 2
      surveys of anglers to determine how often tiger salamanders are used as bait and
      how often they are released into fishing waters by anglers, and organized bait
      shop surveys to determine whether tiger salamanders are released back into the
      wild after being housed in bait shops. Ranaviruses were detected in the tiger
      salamander bait trade in Arizona, Colorado, and New Mexico, and Bd was detected
      in Arizona bait shops. Ranaviruses were spread geographically through the bait
      trade. All tiger salamanders in the bait trade were collected from the wild, and
      in general they moved east to west and north to south, bringing with them their
      multiple ranavirus strains. Finally, 26-73% of anglers used tiger salamanders as
      fishing bait, 26-67% of anglers released tiger salamanders bought as bait into
      fishing waters, and 4% of bait shops released tiger salamanders back into the
      wild after they were housed in shops with infected animals. The tiger salamander
      bait trade in the western United States is a useful model for understanding the
      consequences of the unregulated anthropogenic movement of amphibians and their
      pathogens through trade.

PMID- 18717689
TI  - Relative importance of the area and shape of patches to the diversity of multiple
      taxa.
AB  - Although enhancing reserve shape has been suggested as an alternative to
      enlarging nature reserves, the importance of reserve shape relative to reserve
      area remains unclear. Here we examined the relative importance of area and shape
      of forest patches to species richness, species composition, and species abundance
      (abundance of each species) for 3 taxa (33 birds, 41 butterflies, and 91 forest
      floor plants) in a fragmented landscape in central Hokkaido, northern Japan. We
      grouped the species according to their potential edge responses (interior-,
      neutral-, and edge-species groups for birds and forest-floor plants, woodland-
      and open-land-species groups for butterflies) and analyzed them separately. We
      used a shape index that was independent of area as an index of shape
      circularization. Hierarchical partitioning and variation partitioning revealed
      that patch area was generally more important than patch shape for species
      richness and species composition of birds and butterflies. For forest-floor
      plants, effects of patch area and shape were small, whereas effects of local
      forest structure were large. Patch area and circularization generally increased
      abundances of interior species of birds and forest-floor plants and woodland
      species of butterflies. Nevertheless, only patch circularization increased
      abundances of 1 woodland species of butterfly and 2 and 6 interior species of
      birds and forest-floor plants, respectively. We did not find any significant
      interaction effects between patch area and shape. Our results suggest that
      although reserves generally should be large and circular, there is a trade-off
      between patch area and shape, which should be taken into consideration when
      managing reserves.

PMID- 18717690
TI  - Current status of marine protected areas in latin america and the Caribbean.
AB  - Marine protected areas (MPAs), including no-take marine reserves (MRs), play an
      important role in the conservation of marine biodiversity. We document the status
      of MPAs and MRs in Latin America and the Caribbean, where little has been
      reported on the scope of such protection. Our survey of protected area databases,
      published and unpublished literature, and Internet searches yielded information
      from 30 countries and 12 overseas territories. At present more than 700 MPAs have
      been established, covering more than 300,000 km(2) or 1.5% of the coastal and
      shelf waters. We report on the status of 3 categories of protection: MPAs
      (limited take throughout the area), MRs (no-take throughout the area), and mixed
      use (a limited-take MPA that contains an MR). The majority of protected areas in
      Latin America and the Caribbean are MPAs, which allow some or extensive
      extractive activities throughout the designated area. These 571 sites cover
      51,505 km(2) or 0.3% of coastal and shelf waters. There are 98 MRs covering
      16,862 km(2) or 0.1% of the coastal and shelf waters. Mixed-use MPAs are the
      fewest in number (87), but cover the largest area (236,853 km(2), 1.2%). Across
      Latin America and the Caribbean, many biogeographic provinces are
      underrepresented in these protected areas. Large coastal regions remain
      unprotected, in particular, the southern Pacific and southern Atlantic coasts of
      South America. Our analysis reveals multiple opportunities to strengthen marine
      conservation in Latin America and the Caribbean by improving implementation,
      management, and enforcement of existing MPAs; adding new MPAs and MRs
      strategically to enhance connectivity and sustainability of existing protection;
      and establishing new networks of MPAs and MRs or combinations thereof to enhance
      protection where little currently exists.

PMID- 18717691
TI  - Predicting risk of habitat conversion in native temperate grasslands.
AB  - Native grasslands that support diverse populations of birds are being converted
      to cropland at an increasing rate in the Prairie Pothole Region of North America.
      Although limited funding is currently available to mitigate losses, accurate
      predictions of probability of conversion would increase the efficiency of
      conservation measures. We studied conversion of native grassland to cropland in
      the Missouri Coteau region of North and South Dakota (U.S.A.) during 1989-2003.
      We estimated the probability of conversion of native grassland to cropland with
      satellite imagery and logistic regression models that predicted risk of
      conversion and by comparing the overlap between areas of high biological value
      and areas most vulnerable to conversion. Annualized probability of conversion was
      0.004, and 36,540 ha of native grassland were converted to cropland during the
      period of our study. Our predictive models fit the data and correctly predicted
      70% of observed conversions of grassland. Probability of conversion varied
      spatially and was correlated with landscape features like amount of surrounding
      grassland, slope, and soil productivity. Tracts of high biological value were not
      always at high risk of conversion. We concluded the most biologically valuable
      areas that are most vulnerable to conversion should be prioritized for
      conservation. This approach can be applied broadly to other systems and offers
      great utility for implementing conservation in areas with spatially variable
      biological value and probability of conversion.

PMID- 18717692
TI  - New genetic approach to detecting individuals of rare and endangered species.
AB  - Many rare and endangered species are difficult to locate, observe, and study.
      Consequently, many individuals, breeding pairs, and even populations of such
      species could remain undetected. Genetic markers can potentially be used to
      detect the existence of undiscovered individuals and populations, and we propose
      a method to do so that requires 3 conditions. First, sampling of the known
      population(s) of the target species must be comprehensive. Second, the species
      must display a reasonable level of philopatry and genetic structuring. Third,
      individuals must be able to be caught outside of breeding locations (e.g., at
      courtship or feeding areas, in flight), and the level of recapture must be
      reasonably high. We applied our method to the Chatham Island Taiko (Pterodroma
      magentae), one of the world's most endangered seabirds. We sequenced the Taiko
      mitochondrial cytochrome b gene and both copies of a fragment of the duplicated
      domain I of the control region. Twenty-one haplotypes were revealed, including 4
      (19%) not found in birds at known burrows. These results suggest there are more
      burrow groups yet to be located. The species is a pelagic gadfly petrel that
      inhabits land only in the breeding season during which it is nocturnal and nests
      in burrows. Taiko burrows are situated in dense forest in a remote area of
      Chatham Island, and are consequently difficult to locate and study. It is
      important that all Taiko burrows be discovered to enable monitoring and
      protection of the birds from exotic predators.

PMID- 18717693
TI  - A global baseline for spawning aggregations of reef fishes.
AB  - Species that periodically and predictably congregate on land or in the sea can be
      extremely vulnerable to overexploitation. Many coral reef fishes form spawning
      aggregations that are increasingly the target of fishing. Although serious
      declines are well known for a few species, the extent of this behavior among
      fishes and the impacts of aggregation fishing are not appreciated widely. To
      profile aggregating species globally, establish a baseline for future work, and
      strengthen the case for protection, we (as members of the Society for the
      Conservation of Reef Fish Aggregations) developed a global database on the
      occurrence, history, and management of spawning aggregations. We complemented the
      database with information from interviews with over 300 fishers in Asia and the
      western Pacific. Sixty-seven species, mainly commercial, in 9 families aggregate
      to spawn in the 29 countries or territories considered in the database. Ninety
      percent of aggregation records were from reef pass channels, promontories, and
      outer reef-slope drop-offs. Multispecies aggregation sites were common, and
      spawning seasons of most species typically lasted <3 months. The best-documented
      species in the database, the Nassau grouper (Epinephelus striatus), has undergone
      substantial declines in aggregations throughout its range and is now considered
      threatened. Our findings have important conservation and management implications
      for aggregating species given that exploitation pressures on them are increasing,
      there is little effective management, and 79% of those aggregations sufficiently
      well documented were reported to be in decline. Nonetheless, a few success
      stories demonstrate the benefits of aggregation management. A major shift in
      perspective on spawning aggregations of reef fish, from being seen as
      opportunities for exploitation to acknowledging them as important life-history
      phenomena in need of management, is urgently needed.

PMID- 18717694
TI  - Shifting cultivation and biodiversity conservation in Bhutan.

PMID- 18717695
TI  - Gastrointestinal bacterial transmission among humans, mountain gorillas, and
      livestock in Bwindi Impenetrable National Park, Uganda.
AB  - Habitat overlap can increase the risks of anthroponotic and zoonotic pathogen
      transmission between humans, livestock, and wild apes. We collected Escherichia
      coli bacteria from humans, livestock, and mountain gorillas (Gorilla gorilla
      beringei) in Bwindi Impenetrable National Park, Uganda, from May to August 2005
      to examine whether habitat overlap influences rates and patterns of pathogen
      transmission between humans and apes and whether livestock might facilitate
      transmission. We genotyped 496 E. coli isolates with repetitive extragenic
      palindromic polymerase chain reaction fingerprinting and measured susceptibility
      to 11 antibiotics with the disc-diffusion method. We conducted population genetic
      analyses to examine genetic differences among populations of bacteria from
      different hosts and locations. Gorilla populations that overlapped in their use
      of habitat at high rates with people and livestock harbored E. coli that were
      genetically similar to E. coli from those people and livestock, whereas E. coli
      from gorillas that did not overlap in their use of habitats with people and
      livestock were more distantly related to human or livestock bacteria. Thirty-five
      percent of isolates from humans, 27% of isolates from livestock, and 17% of
      isolates from gorillas were clinically resistant to at least one antibiotic used
      by local people, and the proportion of individual gorillas harboring resistant
      isolates declined across populations in proportion to decreasing degrees of
      habitat overlap with humans. These patterns of genetic similarity and antibiotic
      resistance among E. coli from populations of apes, humans, and livestock indicate
      that habitat overlap between species affects the dynamics of gastrointestinal
      bacterial transmission, perhaps through domestic animal intermediates and the
      physical environment. Limiting such transmission would benefit human and domestic
      animal health and ape conservation.

PMID- 18717696
TI  - Changes in arthropod assemblages along a wide gradient of disturbance in Gabon.
AB  - Searching for indicator taxa representative of diverse assemblages, such as
      arthropods, is an important objective of many conservation studies. We evaluated
      the impacts of a wide gradient of disturbance in Gabon on a range of arthropod
      assemblages representing different feeding guilds. We examined 4 x 10(5)
      arthropod individuals from which 21 focal taxa were separated into 1534
      morphospecies. Replication included the understory of 3 sites in each of 4
      different stages of forest succession and land use (i.e., habitats) after logging
      (old and young forests, savanna, and gardens). We used 3 complementary sampling
      methods to survey sites throughout the year. Overall differences in arthropod
      abundance and diversity were greatest between forest and open habitats, and
      cleared forest invaded by savanna had the lowest abundance and diversity. The
      magnitude of faunal differences was much smaller between old and young forests.
      When considered at this local scale, anthropogenic modification of habitats did
      not result in a monotonous decline of diversity because many herbivore pests and
      their associated predators and parasitoids were abundant and diverse in gardens,
      where plant productivity was kept artificially high year-round through watering
      and crop rotation. We used a variety of response variables to measure the
      strength of correlations across survey locations among focal taxa. These could be
      ranked as follows in terms of decreasing number of significant correlations:
      species turnover > abundance > observed species richness > estimated species
      richness > percentage of site-specific species. The number of significant
      correlations was generally low and apparently unrelated to taxonomy or guild
      structure. Our results emphasize the value of reporting species turnover in
      conservation studies, as opposed to simply measuring species richness, and that
      the search for indicator taxa is elusive in the tropics. One promising
      alternative might be to consider "predictor sets" of a small number of taxa
      representative of different functional groups, as identified in our study.

PMID- 18717697
TI  - Balancing emotion and cognition: a case for decision aiding in conservation
      efforts.
AB  - Despite advances in the quality of participatory decision making for
      conservation, many current efforts still suffer from an inability to bridge the
      gap between science and policy. Judgment and decision-making research suggests
      this gap may result from a person's reliance on affect-based shortcuts in complex
      decision contexts. I examined the results from 3 experiments that demonstrate how
      affect (i.e., the instantaneous reaction one has to a stimulus) influences
      individual judgments in these contexts and identified techniques from the
      decision-aiding literature that help encourage a balance between affect-based
      emotion and cognition in complex decision processes. In the first study, subjects
      displayed a lack of focus on their stated conservation objectives and made
      decisions that reflected their initial affective impressions. Value-focused
      approaches may help individuals incorporate all the decision-relevant objectives
      by making the technical and value-based objectives more salient. In the second
      study, subjects displayed a lack of focus on statistical risk and again made
      affect-based decisions. Trade-off techniques may help individuals incorporate
      relevant technical data, even when it conflicts with their initial affective
      impressions or other value-based objectives. In the third study, subjects
      displayed a lack of trust in decision-making authorities when the decision
      involved a negatively affect-rich outcome (i.e., a loss). Identifying shared
      salient values and increasing procedural fairness may help build social trust in
      both decision-making authorities and the decision process.

PMID- 18717698
TI  - Demographic consequences of terrestrial habitat loss for pool-breeding
      amphibians: predicting extinction risks associated with inadequate size of buffer
      zones.
AB  - Much of the biodiversity associated with isolated wetlands requires aquatic and
      terrestrial habitat to maintain viable populations. Current federal wetland
      regulations in the United States do not protect isolated wetlands or extend
      protection to surrounding terrestrial habitat. Consequently, some land managers,
      city planners, and policy makers at the state and local levels are making an
      effort to protect these wetland and neighboring upland habitats. Balancing human
      land-use and habitat conservation is challenging, and well-informed land-use
      policy is hindered by a lack of knowledge of the specific risks of varying
      amounts of habitat loss. Using projections of wood frog (Rana sylvatica) and
      spotted salamander (Ambystoma maculatum) populations, we related the amount of
      high-quality terrestrial habitat surrounding isolated wetlands to the decline and
      risk of extinction of local amphibian populations. These simulations showed that
      current state-level wetland regulations protecting 30 m or less of surrounding
      terrestrial habitat are inadequate to support viable populations of pool-breeding
      amphibians. We also found that species with different life-history strategies
      responded differently to the loss and degradation of terrestrial habitat. The
      wood frog, with a short life span and high fecundity, was most sensitive to
      habitat loss and isolation, whereas the longer-lived spotted salamander with
      lower fecundity was most sensitive to habitat degradation that lowered adult
      survival rates. Our model results demonstrate that a high probability of local
      amphibian population persistence requires sufficient terrestrial habitat, the
      maintenance of habitat quality, and connectivity among local populations. Our
      results emphasize the essential role of adequate terrestrial habitat to the
      maintenance of wetland biodiversity and ecosystem function and offer a means of
      quantifying the risks associated with terrestrial habitat loss and degradation.

PMID- 18717699
TI  - Paternal correlates of cognitive and behavioral functioning in children with
      myelomeningocele.
AB  - This study examined paternal correlates of the cognitive and behavioral
      functioning of children with myelomeningocele, when controlling for maternal and
      biological/child correlates as possible sources of variance. Participants were 48
      parent dyads of children with myelomeningocele (21 males, 27 females) between the
      ages of 4 and 12 years (mean 8y, 2mo, SD 2y 3mo). Lesion levels of participants
      ranged from the thoracic to sacral (thoracic-L3: n=15; L4-L5: n=15; sacral or
      lipomeningocele: n=18), of whom 38 had been shunted for hydrocephalus. Half of
      the participants (n=24) were community ambulators. Potential predictors of
      cognitive and behavioral functioning included paternal and maternal parenting
      stress, as assessed by the Parenting Stress Index - Short Form paternal, and
      maternal perceptions of support and resources, as assessed by the Family Resource
      Scale and the Family Support Scale, and child medical severity. Paternal
      variables significantly correlated with behavioral functioning but not with
      cognitive functioning. Regression analyses revealed that paternal personal
      distress and maternal perceived adequacy of social support accounted for
      significant variance in overall child behavioral functioning. Only child medical
      severity and annual household income explained significant variance in overall
      child cognitive functioning. These findings add to the growing body of theory and
      research documenting that fathers make unique and significant contributions to
      child adjustment in children with myelomeningocele. Both fathers and mothers need
      to be considered in interventions supporting development and adjustment of
      children with myelomeningocele and their families.

PMID- 18717700
TI  - Institutional, policy and farmer responses to drought: El Nino events and rice in
      the Philippines.
AB  - Droughts are common recurring natural hazards in Asia, and El Nino events are
      particularly severe in the Philippines. This paper explores responses by farm
      households, irrigation system managers, and macro policymakers in the Philippines
      to El Nino. In response to the large 1997-98 El Nino, farmers in one major
      irrigation system significantly diversified their economic activities, hut the
      drought was so acute that many of these activities were not successful.
      Communication between meteorologists and irrigation system managers is strong,
      and irrigation system managers are aware of El Nino events in advance.
      Communication between irrigation system managers and farmer irrigation
      associations is also strong, and together they have developed response options
      that attempt to augment supplies of and more efficiently allocate scarce water.
      Water pricing is not used, however, and lack of cooperation among farmers results
      in sub-optimal outcomes. Macro-level policy responses in terms of rice imports
      and buffer stock management to protect poor consumers have improved substantially
      over time.

PMID- 18717701
TI  - Multiple disasters and policy responses in pre- and post-independence Orissa,
      India.
AB  - 'Multiple disasters' or disasters that occur in 'one specific place' are regular
      events in coastal parts of the state of Orissa in eastern India. Yet the policy
      framework for addressing multiple disasters is weak. This paper aims to show that
      policy responses in pre- and post-independence Orissa have overlooked the effects
      of multiple disasters. Evidence based on a review of the literature and on
      fieldwork indicates that Orissa has a long history of experience of multiple
      disasters due to its unique geographic location, political dislocation, and
      ineffective disaster policies that have focused only on single events. One can
      observe the effects of this even today in Orissa, notably inadequate measures to
      counteract the consequences of multiple disasters at the household level and to
      build people's capacity. This study posits, therefore, that multiple disasters
      deserve good representation in integrated disaster reduction strategies designed
      to mitigate their impacts.

PMID- 18717702
TI  - Ethnicity, politics and inequality: post-tsunami humanitarian aid delivery in
      Ampara District, Sri Lanka.
AB  - The provision of humanitarian aid at times of disaster in multi-ethnic community
      settings may lead to conflict, tension and even the widening of the distance
      between various ethnic groups. That aid agencies distribute humanitarian aid
      directly to affected communities, to speed up recovery, may often lead to chaos
      and the intensification of ethnic sentiments. The new distribution mechanisms
      introduced for the delivery of tsunami aid in Ampara District, Sri Lanka, did not
      recognise local networks and the culture of the ethnically mixed community
      setting. This paper analyses post-tsunami aid distribution in Ampara and shows
      how such an extemporised effort in an ethnically cognisant context increased
      ethnic division, inequality and disorder, while marginalising the poor segments
      of the affected population. It recommends the inclusion of local networks in aid
      dissemination as a measure for improving ethnic neutrality and social harmony in
      disaster-hit multi-ethnic communities.

PMID- 18717703
TI  - Biodiversity versus emergencies: the impact of restocking on Animal Genetic
      Resources after disaster.
AB  - Restocking is a favoured option in supporting livelihoods after a disaster. With
      the depletion of local livestock populations, the introduction of new species and
      breeds will clearly affect biodiversity. Nevertheless, the impact of restocking
      on Animal Genetic Resources has been largely ignored. The aim of this paper,
      therefore, is to examine the consequences of restocking on biodiversity via a
      simple model. Utilising a hypothetical project based on cattle, the model
      demonstrates that more than one-third of the population was related to the
      original restocked animals after three generations. Under conditions of random
      breed selection, the figure declined to 20 per cent. The tool was then applied to
      a donor-led restocking project implemented in Bosnia-Herzegovina. By restocking
      primarily with Simmental cattle, the model demonstrated that the implementation
      of a single restocking project is likely to have accelerated the decline of the
      indigenous Busa breed by a further nine per cent. Thus, greater awareness of the
      long-term implications of restocking on biodiversity is required.

PMID- 18717704
TI  - Spatial localization and time-dependant changes of electrographic high frequency
      oscillations in human temporal lobe epilepsy.
AB  - PURPOSE: High frequency oscillations (HFOs) >200 Hz are believed to be associated
      with epileptic processes. The spatial distribution of HFOs and their evolution
      over time leading up to seizure onset is unknown. Also, recording HFOs through
      conventional intracranial electrodes is not well established. We therefore wished
      to determine whether HFOs could be recorded using commercially available depth
      macroelectrodes. We also examined the spatial distribution and temporal
      progression of HFOs during the transition to seizure activity. METHODS:
      Intracranial electroencephalography (EEG) recordings of 19 seizures were obtained
      from seven patients with temporal lobe epilepsy using commercial depth or
      subdural electrodes. EEG recordings were analyzed for frequency content in five
      spectral bands spanning DC-500 Hz. We examined the spatial distribution of the
      different spectral bands 5 s before and 5 s after seizure onset. Temporal changes
      in the spectral bands were studied in the 30-s period leading up to seizure
      onset. RESULTS: Three main observations were made. First, HFOs (100-500 Hz) can
      be recorded using commercial depth and subdural grid electrodes. Second, HFOs,
      but not <100 Hz oscillations, were localized to channels of ictal onset (100-200,
      400-500 Hz, p < 0.05; 300-400 Hz, p < 0.001). Third, temporal analysis showed
      increased HFO power for approximately 8 s prior to electrographic onset (p <
      0.05). CONCLUSIONS: These results suggest that HFOs can be recorded by depth
      macroelectrodes. Also, HFOs are localized to the region of primary ictal onset
      and can exhibit increased power during the transition to seizure. Thus, HFOs
      likely represent important precursors to seizure initiation.

PMID- 18717705
TI  - Oxcarbazepine, not its active metabolite, potentiates GABAA activation and
      aggravates absence seizures.
AB  - PURPOSE: Studies in genetic absence epileptic rats from Strasbourg (GAERS)
      indicate that enhancement of gamma aminobutyric acid (GABA(A)) receptor activity
      is a critical mechanism in the aggravation of seizures by carbamazepine (CBZ). We
      examined whether structural analogs of CBZ, oxcarbazepine (OXC), and its active
      metabolite, monohydroxy derivative (MHD), also potentiate GABA(A) receptor
      current and aggravate seizures. METHODS: In vitro studies in Xenopus oocytes
      compared the three drugs' effect on GABA(A) receptor currents. In vivo studies
      compared seizure activity in GAERS after intraperitoneal drug administration.
      RESULTS: OXC potentiated GABA(A) receptor current and aggravated seizures in
      GAERS, similarly to the effect of CBZ. Conversely, MHD showed only a minor
      potentiation of GABA(A) receptor current and did not aggravate seizures.
      DISCUSSION: A hydroxyl group at the C-10 position on the CBZ tricyclic structure
      in MHD reduces GABA(A) receptor potentiation and seizure aggravation. Reports of
      the aggravation of absence seizures in patients taking OXC may result from
      circulating unmetabolized OXC rather than MHD.

PMID- 18717706
TI  - Revisiting the role of the insula in refractory partial epilepsy.
AB  - PURPOSE: Recent evidence suggesting that some epilepsy surgery failures could be
      related to unrecognized insular epilepsy have led us to lower our threshold to
      sample the insula with intracerebral electrodes. In this study, we report our
      experience resulting from this change in strategy. METHODS: During the period
      extending from October 2004 to June 2007, 18 patients had an intracranial study
      including 10 with insular coverage. The decision to sample the insula with
      intracerebral electrodes was made in the context of (1) nonlesional parietal lobe
      like epilepsy; (2) nonlesional frontal lobe-like epilepsy; (3) nonlesional
      temporal lobe-like epilepsy; and (4) atypical temporal lobe-like epilepsy.
      RESULTS: Intracerebral recordings confirmed the presence of insular lobe seizures
      in four patients. Cortical stimulation performed in 9 of 10 patients with insular
      electrodes elicited, in decreasing order of frequency, somatosensory,
      viscerosensory, motor, auditory, vestibular, and speech symptoms. DISCUSSION: Our
      results suggest that insular cortex epilepsy may mimic temporal, frontal, and
      parietal lobe epilepsies and that a nonnegligeable proportion of surgical
      candidates with drug-resistant epilepsy have an epileptogenic zone that involves
      the insula.

PMID- 18717707
TI  - Gene therapy in epilepsy.
AB  - Results from animal models suggest gene therapy is a promising new approach for
      the treatment of epilepsy. Several candidate genes such as neuropeptide Y and
      galanin have been demonstrated in preclinical studies to have a positive effect
      on seizure activity. For a successful gene therapy-based treatment, efficient
      delivery of a transgene to target neurons is also essential. To this end,
      advances have been made in the areas of cell transplantation and in the
      development of recombinant viral vectors for gene delivery. Recombinant adeno
      associated viral (rAAV) vectors in particular show promise for gene therapy of
      neurological disorders due to their neuronal tropism, lack of toxicity, and
      stable persistence in neurons, which results in robust, long-term expression of
      the transgene. rAAV vectors have been recently used in phase I clinical trials of
      Parkinson's disease with an excellent safety profile. Prior to commencement of
      phase I trials for gene therapy of epilepsy, further preclinical studies are
      ongoing including evaluation of the therapeutic benefit in chronic models of
      epileptogenesis, as well as assessment of safety in toxicological studies.

PMID- 18717708
TI  - Source localization of scalp-EEG interictal spikes in posterior cortex epilepsies
      investigated by HR-EEG and SEEG.
AB  - PURPOSE: To determine the validity of scalp-electroencephalography (EEG)
      interictal spike (IIS) source localization in posterior cortex epilepsies (PCE).
      METHODS: Eleven patients with drug-resistant PCE were studied with high
      resolution EEG (HR-EEG) and stereoelectroencephalography (SEEG). Sixty-four scalp
      channels, a realistic head model, and different algorithms [multiple signal
      classification (MUSIC) and equivalent current dipoles] were used. Results were
      compared to intracerebral SEEG recordings. For SEEG, a semiautomatic detection of
      intracerebral IIS was used, allowing a classification of intracerebral IIS into
      one of three groups: Medial, lateral, and mediolateral. RESULTS: In the medial
      group (two patients), scalp-EEG IIS were usually absent for one patient whereas
      for the other, scalp-EEG was misleading. Indeed, scalp-EEG IIS had a posterior
      projection, predominantly contralateral to the source. In the lateral group (two
      patients), scalp-EEG IIS were subcontinuous and accurately localized. In the
      mediolateral group (seven patients), intracerebral interictal distribution was
      complex and bilateral for four of seven patients. Source localizations were able
      to determine only a part, whether lateral or medial, of the intracerebral
      interictal distribution. DISCUSSION: The accuracy of scalp-EEG IIS source
      localization is dependant on the type of intracerebral interictal distribution.
      In the most frequent type of PCE, patients proved to have a complex interictal
      distribution between both medial and lateral cortices, and source localizations
      always underestimated intracerebral IIS. In cases where intracranial sources were
      quite focal, surface EEG sources were localized with accuracy, even in medial
      occipital lobe structures.

PMID- 18717709
TI  - Two novel ALDH7A1 (antiquitin) splicing mutations associated with pyridoxine
      dependent seizures.
AB  - Pyridoxine-dependent seizures (PDS) is a rare autosomal recessive disorder
      causing intractable seizures in neonates and infants. Patients are typically
      resistant to conventional anticonvulsants but respond well to the administration
      of pyridoxine. We report two unrelated patients affected with PDS as a result of
      alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency caused by
      pathogenic ALDH7A1/antiquitin mutations. Two of the three reported mutations are
      novel and result in erroneous splicing, as showed by messenger RNA (mRNA)
      studies. So far, the vast majority of the patients clinically diagnosed as PDS
      show alpha-AASA dehydrogenase deficiency, caused by mutations in the ALDH7A1
      gene. However, despite the availability of reliable biomarkers, early
      consideration of a pyridoxine trial is still the most important issue in a child
      with therapy-resistant seizures.

PMID- 18717710
TI  - A blinded, crossover study of the efficacy of the ketogenic diet.
AB  - Despite over 80 years of use, the ketogenic diet (KD) has never been tested in a
      blinded manner. Twenty children with intractable Lennox-Gastaut syndrome (LGS)
      were fasted 36 h and then randomized to receive the classic KD in conjunction
      with a solution containing either 60 g/day of glucose or saccharin. Parents and
      physicians were blinded to both the solution composition and level of ketosis. A
      crossover to the KD with the alternate solution occurred following the sixth day
      and a repeat fast. A 24-h electroencephalography (EEG) was obtained at baseline
      and after each arm. After administration of the solution, there was moderate
      evidence of a reduction in parent-reported seizures between the glucose and
      saccharin arms, with a median difference of 1.5 seizures per day (p = 0.07).
      There was no reduction in the number of EEG-identified events, with a median
      reduction of 7 events per day (p = 0.33). Ketosis was not completely eliminated
      in the glucose-added arm.

PMID- 18717712
TI  - Outcome after corticoamygdalohippocampectomy in patients with refractory temporal
      lobe epilepsy and mesial temporal sclerosis without preoperative ictal recording.
AB  - PURPOSE: We report on the surgical outcome obtained in patients with refractory
      temporal lobe epilepsy with mesial temporal sclerosis (MTS) who were evaluated
      preoperatively without ictal recording and were submitted to
      corticoamygdalohippocampectomy. METHODS: Two hundred twelve patients with
      refractory temporal lobe epilepsy were evaluated by means of clinical history,
      neurological examination, interictal electroencephalography (EEG), magnetic
      resonance imaging (MRI), and neuropsychological testing. MRI disclosed unilateral
      MTS in all patients. All patients were submitted to
      corticoamygdalohippocampectomy at the side determined by MRI. RESULTS: Interictal
      EEG showed unilateral temporal lobe spiking in 176 patients; in 36 patients,
      bilateral discharges were found. Mean follow-up time was 2.7 years. One hundred
      ninety-four patients (92%) were classified as Engel's class I. Eighteen patients
      (8%) were rated as Engel's class II. Thirty-two out of 36 patients, in whom
      bilateral discharges were found, were in Engel's class I. Sixty percent of the
      patients had an improvement in memory function related to the nonoperated
      temporal lobe. Fifty-nine percent of the patients had a 10-point increase in
      general IQ postoperatively. Verbal memory decline was noted in three patients.
      Pathological examination showed MTS in all patients. CONCLUSIONS: It is possible
      to adequately select good surgical candidates for temporal lobe resection using
      MRI and interictal EEG alone. In patients with MRI-defined MTS, we should expect
      a 90% postoperative remission rate. Cognitive decline was very rarely seen in
      this patient population. The finding of MTS on MRI is the single most important
      prognostic factor for good outcome after temporal lobe surgery.

PMID- 18717711
TI  - Preoperative amygdala fMRI in temporal lobe epilepsy.
AB  - PURPOSE: Anterior temporal lobe resections (ATLR) benefit 70% of patients with
      refractory mesial temporal lobe epilepsy (TLE), but may be complicated by
      emotional disturbances. We used functional magnetic resonance imaging (fMRI) to
      investigate the role of the amygdala in processing emotions in TLE and whether
      this may be a potential preoperative predictive marker for emotional disturbances
      following surgery. METHODS: We studied 54 patients with refractory mesial TLE due
      to hippocampal sclerosis (28 right, 26 left) and 21 healthy controls using a
      memory encoding fMRI paradigm, which included viewing fearful and neutral faces.
      Twenty-one TLE patients (10 left, 11 right) subsequently underwent ATLR. Anxiety
      and depression were assessed preoperatively and 4 months postoperatively using
      the Hospital Anxiety and Depression Scale. RESULTS: On viewing fearful faces,
      healthy controls demonstrated left lateralized, while right TLE patients showed
      bilateral amygdala activation. Left TLE patients had significantly reduced
      activation in left and right amygdalae compared to controls and right TLE
      patients. In right TLE patients, left and right amygdala activation was
      significantly related to preoperative anxiety and depression levels, and
      preoperative right amygdala activation correlated significantly with
      postoperative change of anxiety and depression scores, characterized by greater
      increases in anxiety and depression in patients with greater preoperative
      activation. No such correlations were seen for left TLE patients. DISCUSSION: The
      fearful face fMRI paradigm is a reliable method for visualizing amygdala
      activation in controls and patients with mesial TLE. Activation of the right
      amygdala preoperatively was predictive of emotional disturbances following right
      ATLR.

PMID- 18717713
TI  - Imaging seizure activity: a combined EEG/EMG-fMRI study in reading epilepsy.
AB  - PURPOSE: To characterize the spatial relationship between activations related to
      language-induced seizure activity, language processing, and motor control in
      patients with reading epilepsy. METHODS: We recorded and simultaneously monitored
      several physiological parameters [voice-recording, electromyography (EMG),
      electrocardiography (ECG), electroencephalography (EEG)] during blood oxygen
      level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in nine
      patients with reading epilepsy. Individually tailored language paradigms were
      used to induce and record habitual seizures inside the MRI scanner. Voxel-based
      morphometry (VBM) was used for structural brain analysis. Reading-induced
      seizures occurred in six out of nine patients. RESULTS: One patient experienced
      abundant orofacial reflex myocloni during silent reading in association with
      bilateral frontal or generalized epileptiform discharges. In a further five
      patients, symptoms were only elicited while reading aloud with self-indicated
      events. Consistent activation patterns in response to reading-induced myoclonic
      seizures were observed within left motor and premotor areas in five of these six
      patients, in the left striatum (n = 4), in mesiotemporal/limbic areas (n = 4), in
      Brodmann area 47 (n = 3), and thalamus (n = 2). These BOLD activations were
      overlapping or adjacent to areas physiologically activated during language and
      facial motor tasks. No subtle structural abnormalities common to all patients
      were identified using VBM, but one patient had a left temporal ischemic lesion.
      DISCUSSION: Based on the findings, we hypothesize that reflex seizures occur in
      reading epilepsy when a critical mass of neurons are activated through a
      provoking stimulus within corticoreticular and corticocortical circuitry
      subserving normal functions.

PMID- 18717714
TI  - Periictal diffusion abnormalities of the thalamus in partial status  epilepticus.
AB  - PURPOSE: To identify and describe thalamic dysfunction in patients with temporal
      as well as extratemporal status epilepticus (SE) and to also analyze the specific
      clinical, radiological, and electroencephalography (EEG) characteristics of
      patients with acute thalamic involvement. METHODS: We retrospectively identified
      patients who presented with clinical and electrographic evidence of partial SE
      and had thalamic abnormalities on diffusion-weighted imaging (DWI) within 5 days
      of documentation of lateralized epileptiform discharges (group 1). The spatial
      and temporal characteristics of the periodic lateralized epileptiform discharges
      (PLEDs) and the recorded electrographic seizures were analyzed and correlated
      with magnetic resonance imaging (MRI)-DWI hyperintense lesions. The findings of
      group 1 patients were compared with those of patients with partial SE without
      thalamic abnormalities on DWI (group 2). RESULTS: The two groups were similar
      with regard to clinical presentation and morphology of epileptiform discharges.
      Group 1 patients had thalamic hyperintense lesions on DWI that appeared in the
      region of the pulvinar nucleus, ipsilateral to the epileptiform activity.
      Statistically significant relationship was noted between the presence of thalamic
      lesions and ipsilateral cortical laminar involvement (p = 0.039) as well as
      seizure origin in the posterior quadrants (p = 0.038). A trend towards PLEDs
      originating in the posterior quadrants was also noted (p = 0.077). DISCUSSION:
      Thalamic DWI hyperintense lesions may be observed after prolonged partial SE and
      are likely the result of excessive activity in thalamic nuclei having reciprocal
      connections with the involved cortex. The thalamus likely participates in the
      evolution and propagation of partial seizures in SE.

PMID- 18717715
TI  - Decreased expression of synaptic vesicle protein 2A, the binding site for
      levetiracetam, during epileptogenesis and chronic epilepsy.
AB  - PURPOSE: We previously showed that gene expression of synaptic vesicle protein 2A
      (SV2A), the binding site for the antiepileptic drug levetiracetam, is reduced
      during epileptogenesis in the rat. Since absence of SV2A has been associated with
      increased epileptogenicity, changes in expression of SV2A could have consequences
      for the progression of epilepsy. Therefore we investigated hippocampal SV2A
      protein expression of temporal lobe epilepsy (TLE) patients and in rats during
      epileptogenesis and in the chronic epileptic phase. METHODS: SV2A
      immunocytochemistry and Western blot analysis were performed on the hippocampus
      of autopsy controls, patients that died from status epilepticus (SE), and
      pharmacoresistant TLE patients. In addition, in epileptic rats, SV2A expression
      was determined after SE during the acute, latent, and chronic epileptic phase.
      RESULTS: In control tissue, presynaptic SV2A was expressed in all hippocampal
      subfields, with strongest expression in mossy fiber terminals. SV2A positive
      puncta were distributed in a patchy pattern over the somata and dendrites of
      neurons. SV2A decreased throughout the hippocampus of TLE patients with
      hippocampal sclerosis (HS), compared to autopsy control, SE, and non-HS tissue.
      In most rats, SV2A was already decreased in the latent period especially in the
      inner molecular layer and stratum lucidum. Similarly as in humans, SV2A was also
      decreased throughout the hippocampus of chronic epileptic rats, specifically in
      rats with a progressive form of epilepsy. DISCUSSION: These data support previous
      findings that reduced expression of SV2A could contribute to the increased
      epileptogenicity. Whether this affects the effectiveness of levetiracetam needs
      to be further investigated.

PMID- 18717716
TI  - Newly diagnosed single unprovoked seizures and epilepsy in Stockholm, Sweden:
      First report from the Stockholm Incidence Registry of Epilepsy (SIRE).
AB  - PURPOSE: To describe and report initial findings of a system for prospective
      identification and follow-up of patients with newly diagnosed single unprovoked
      seizures and epilepsy in Stockholm, Sweden, the Stockholm Incidence Registry of
      Epilepsy (SIRE). METHODS: From September 2001 through August 2004, a surveillance
      system has been in use to identify incident cases of first unprovoked seizures
      (neonatal seizures excluded) and epilepsy among residents of Northern Stockholm,
      an urban area with approximately 998,500 inhabitants. Potential cases are
      identified through multiple mechanisms: Network of health care professionals,
      medical record screening in specific hospital units, including outpatient
      clinics, emergency room services, and review of requests for
      electroencephalography (EEG) examination. Potential cases are classified 6 months
      after the index seizure based on review of medical records. RESULTS: After
      screening approximately 10,500 EEG requests and 3,300 medical records, 1,015
      persons met the criteria for newly diagnosed unprovoked seizures (430 single
      seizures; 585 epilepsy). The crude incidence for first unprovoked seizures and
      epilepsy was 33.9/100,000 person years, (the same adjusted to the European
      Standard Million), highest the first year of life (77.1/100,000) and in the
      elderly. No cause could be identified in 62.4%. CONCLUSIONS: We have established
      a sustainable system for prospective identification of new onset epilepsy cases
      in Stockholm. Despite a possible under-ascertainment, the registry provides a
      useful starting point for follow-up studies.

PMID- 18717717
TI  - Modulatory effects of anodal transcranial direct current stimulation on
      perception and pain thresholds in healthy volunteers.
AB  - BACKGROUND AND PURPOSE: We aimed to evaluate whether transcranial direct current
      stimulation (tDCS) is effective in modulating sensory and pain perception
      thresholds in healthy subjects as to further explore mechanisms of tDCS in pain
      relief. METHODS: Twenty healthy subjects received stimulation with tDCS under
      four different conditions of stimulation: anodal tDCS of the primary motor cortex
      (M1), dorsolateral prefrontal cortex (DLPFC), occipital cortex (V1), and sham
      tDCS. The order of conditions was randomized and counterbalanced across subjects.
      Perception threshold and pain threshold to peripheral electrical stimulation of
      the right index finger were evaluated by a blinded rater. RESULTS: The results
      showed a significant effect of the interaction time versus stimulation condition
      for perception (P = 0.046) and pain threshold (P = 0.015). Post hoc comparisons
      revealed that anodal stimulation of M1 increased both perception (P < 0.001,
      threshold increase of 6.5%) and pain (P = 0.001, threshold increase of 8.3%)
      thresholds significantly, whilst stimulation of the DLPFC increased pain
      threshold only (P = 0.046, threshold increase of 10.0%). There were no
      significant effects for occipital or sham stimulation. CONCLUSIONS: These results
      show that both M1 and DLFPC anodal tDCS can be used to modulate pain thresholds
      in healthy subjects; thus, the mechanism of tDCS in modulating pain involves
      pathways that are independent of abnormal pain-related neural activity.

PMID- 18717718
TI  - Mechanism of tuberothalamic infarction.
AB  - BACKGROUND AND PURPOSE: The tuberothalamic artery (TTA), one of the arteries
      supplying the paramedian thalamic area, is peculiar because it originates from
      the posterior communicating artery (p-comA), which connects the vertebrobasilar
      and carotid systems. METHODS: From Stroke Registry, 23 consecutive patients with
      an acute infarction involving the TTA were selected. We investigated the
      mechanism of TTA infarction. RESULTS: Fourteen of 23 patients (61%) had
      coexisting infarctions outside the TTA territory (carotid in three,
      vertebrobasilar in seven, and both carotid and vertebrobasilar arteries in four
      patients). Coexisting lesions were most common in the posterior
      thalamoperforating arterial territory (seven patients). Eleven out of 14 patients
      (79%) with coexisting lesions had embolic sources from the heart or proximal
      atherosclerotic arteries, and cardioembolism was the most common mechanism.
      However, eight of the nine patients with isolated tuberothalamic lesions were
      classified as small vessel occlusions. More patients with embolic sources had
      visible p-comA or fetal-type posterior cerebral arteries. The vertebrobasilar
      arterial system played a more dominant role in developing tuberothalamic
      infarction than the carotid arterial system. CONCLUSIONS: Isolated TTA
      infarctions are rare and mostly because of small vessel occlusion. Patients with
      coexisting infarctions outside TTA territory usually have an embolic source,
      predominantly vertebral artery atherosclerosis.

PMID- 18717719
TI  - Stroke and multiple peripheral thrombotic events in an adult with varicella.

PMID- 18717720
TI  - Charcot-Marie-Tooth type X: unusual phenotype of a novel CX32 mutation.
AB  - BACKGROUND: X-linked Charcot-Marie-Tooth disease (CMTX), caused by mutations in
      the gene encoding connexin32, is the second most common form of inherited
      demyelinating neuropathy, next to CMT 1A, and accounts for 10-20% of all
      hereditary demyelinating neuropathies. AIMS OF THE STUDY: To describe clinical
      and electrophysiological data of an Italian family carrying a novel mutation in
      the Cx32 gene. PATIENTS AND METHODS: Clinical, electrophysiological, and genetic
      findings of three patients carrying the Ser128Leu mutation in the intracellular
      domain of the Cx32 gene were reported. Brain MRI studies were also performed.
      RESULTS: In our family the disease was characterized by a moderate-to-severe
      polyneuropathy affecting similarly males as well females. In the proband the
      phenotype was quite unusual in terms of late-onset, rapidity of evolution and
      severity. Abnormal brain MRI in association with CNS symptoms were also observed.
      Both sons had also clinical evidence of CNS involvement. CONCLUSIONS: The
      Ser128Leu mutation in the Cx-32 gene is a novel substitution, which has not been
      reported so far. This novel mutation could be added to the group of Cx-32
      mutations with CNS phenotypes. The identification of new CMTX causing mutations
      is a crucial step for carrier detection and pre-symptomatic diagnosis.

PMID- 18717721
TI  - Misdiagnosis in epilepsy: a review and recognition of diagnostic uncertainty.
AB  - The diagnosis of first seizure or epilepsy may be challenging and misdiagnosis
      can occur. Studies carried out in various settings have reported misdiagnosis
      rates of between 4.6% and 30%. Misdiagnosis can lead to serious consequences
      including driving and employment restrictions and inappropriate treatments. Most
      studies focus on ways of reducing misdiagnosis. However, in some cases, it may be
      difficult to make a definite diagnosis at initial presentation. This is because
      of a number of reasons including overlapping clinical features with other
      conditions, inadequate available history and limitations of investigations.
      Consequently, diagnostic uncertainty is inevitable in epilepsy, although few
      studies acknowledge this. In this paper we review the literature on misdiagnosis
      rates, analyse reasons for misdiagnosis and consider limitations of available
      investigations. We propose that diagnostic uncertainty in epilepsy should be more
      widely acknowledged and addressed, and that this may reduce misdiagnosis rates.

PMID- 18717722
TI  - Blood pressure is not associated with haematoma enlargement in acute
      intracerebral haemorrhage.
AB  - BACKGROUND AND PURPOSE: We performed an observational study that compared
      baseline and subsequent blood pressure (BP) measurements and its association with
      haematoma enlargement (HE) in patients with intracerebral haemorrhage (ICH).
      METHODS: We prospectively studied consecutive patients with supratentorial
      spontaneous ICH within the first 6 h after the onset of symptoms. HE was defined
      as an increase >or=33% in the volume of haematoma on the CT obtained 24-48 h
      after the onset of symptoms as compared with the CT at admission. We recorded
      systolic BP (SBP), diastolic BP (DBP) and mean BP (MBP) at admission and at 6,
      12, 18 and 24 h after onset; the maximum SBP, DBP and MBP during the study
      period; the maximum SBP and DBP within intervals; the mean of all BP readings;
      administration of antihypertensive agents. RESULTS: We studied 60 patients whose
      mean age was 72.1 +/- 11.3 years. HE was observed in 27 (45%) patients. No
      statistically significant differences were observed in any of the analyses that
      compared BP parameters between the HE and non-HE groups (two-way anova).
      CONCLUSIONS: In an exploratory analysis, we did not find an association between
      BP and HE within the first 24 h after an acute ICH.

PMID- 18717723
TI  - Cytokine IL-1 beta but not IL-1 alpha promoter polymorphism is associated with
      Alzheimer disease in a population from the Canary Islands, Spain.
AB  - AIMS: Previous studies have reported the presence of low-grade inflammation in
      Alzheimer disease (AD). Based on these data, our work attempts to investigate the
      effects of some promoter polymorphisms of pro-inflammatory cytokines [interleukin
      (IL)-1 alpha and IL-1 beta] on AD. PATIENTS AND METHODS: A PCR-RFLP technique was
      used to analyze the promoter polymorphisms of both IL-1 alpha (-889 C/T) and IL-1
      beta (-511 C/T) and the APOE genotype from the DNA samples of 282 patients
      (according to NINCDS-ADRDA criteria) and 312 control subjects. RESULTS: (i) The
      risk of developing AD in our population was associated with the IL-1 beta (-511
      C/T) promoter polymorphism; (ii) such risk was independent of the risk factor
      allele in the APOE gene (APOE4); and (iii) the IL-1 alpha promoter polymorphism (
      889 C/T) was not associated with the disease. CONCLUSION: In our population, IL-1
      beta promoter polymorphism (-511 C/T) is an independent risk factor for AD.

PMID- 18717724
TI  - Reduced oxygen due to high-altitude exposure relates to atrophy in motor-function
      brain areas.
AB  - BACKGROUND AND PURPOSE: At high altitudes barometric pressure is reduced and,
      thus, less oxygen is inhaled. Reduced oxygen concentration in brain tissue can
      lead to cerebral damage and neurological and cognitive deficits. The present
      study was designed to explore the effects of high-altitude exposure using a
      quantitative MRI technique, voxel-based morphometry. METHODS: We studied nine
      world-class mountain climbers before (baseline) and after (follow-up) an
      extremely high-altitude ascent of Everest and K2. We investigated the effects of
      repeated extremely high-altitude exposures by comparing mountain climbers' scans
      at baseline with scans of 19 controls. In addition, we measured the effects of a
      single extremely high-altitude expedition by comparing mountain climbers' scans
      at baseline and follow-up. RESULTS: A region of reduced white matter
      density/volume was found in the left pyramidal tract near the primary (BA 4) and
      supplementary (BA 6) motor cortex when mountain climbers at baseline were
      compared with controls. Further, when mountain climbers' scans before and after
      the expedition were compared, a region of reduced grey matter density/volume was
      found in the left angular gyrus (BA 39). CONCLUSION: These findings suggest that
      extremely high-altitude exposures may cause subtle white and grey matter changes
      that mainly affect brain regions involved in motor activity.

PMID- 18717725
TI  - Paraneoplastic myasthenia gravis: immunological and clinical aspects.
AB  - Paraneoplastic myasthenia gravis (MG) is accompanied by a neoplasm, usually
      thymoma. In patients with thymoma and a specific genetic make-up, the
      paraneoplastic immune response develops further in thymic remnant or peripheral
      lymphatic tissue. Paraneoplastic MG and late-onset MG (age >or= 50 years) share a
      similar immunological profile with high titin and ryanodine receptor (RyR)
      antibody prevalence. This profile is the most important predictor of clinical
      outcome in paraneoplastic MG. The presence of a thymoma per se does not cause
      more severe MG. MG severity is linked to the patient's immunological profile.
      Paraneoplastic MG causes a distinctive non-limb symptom profile at MG onset,
      characterized by bulbar, ocular, neck, and respiratory symptoms. When the
      diagnosis of paraneoplastic MG is established, the neoplasm should be removed
      surgically. Pre-thymectomy plasmapheresis or iv-IgG should be considered in these
      patients to minimize post-thymectomy MG exacerbation risk. Paraneoplastic MG
      usually continues after thymectomy. The pharmacological treatment of
      paraneoplastic MG does not differ from non-paraneoplastic MG, except for
      tacrolimus that should be considered in difficult cases. Tacrolimus is an
      immunosuppressant acting specifically in RyR antibody positive patients through
      enhancing RyR-related sarcoplasmic calcium release that in theory might be
      blocked by RyR antibodies, causing symptomatic relief in paraneoplastic MG.

PMID- 18717726
TI  - The role of IL-12 and TNF-alpha in AIDP and AMAN.
AB  - BACKGROUND: Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and
      acute motor axonal neuropathy (AMAN) have been described as two major subtypes of
      Guillain-Barre syndrome (GBS); however, the possible difference of their immune
      inflammatory pathogenesis remains unclear. METHODS: In this study, by using FACS
      and enzyme-linked immunosorbent assays analyses, the role of Th1 cytokines tumour
      necrosis factor-alpha (TNF-alpha), interleukin-12 (IL-12) and their receptors on
      peripheral blood mononuclear cells (PBMCs) and in serum concentrations were
      investigated in AIDP and AMAN. RESULTS: The results showed enhanced IL-12, IL
      12R1 in AIDP and TNF-alpha in AMAN during the acute phase, as well as increased
      TNF-alpha and TNFR1 during the plateau phase of AIDP. Intravenous high dose
      immunoglobulin decreased IL-12R1 expression on cells in AIDP, but increased TNF
      alpha and TNFR2 in AMAN. DISCUSSION: Our data suggest that IL-12 promotes disease
      development in AIDP and in contrast to previously inflammatory assumptions, TNF
      alpha may play double roles in GBS. The anti-inflammatory role of TNF-alpha
      realized through TNFR2 in AMAN is possibly a therapeutic mechanism in the IVIg
      treatment of AMAN.

PMID- 18717727
TI  - Epidemiological study of acute encephalitis in Tottori Prefecture, Japan.
AB  - BACKGROUND AND PURPOSE: To conduct an epidemiological survey of acute
      encephalitis focusing on non-herpetic acute limbic encephalitis (NHALE) in
      Tottori Prefecture, western area of Japan. METHODS: A questionnaire survey on the
      annual number of patients aged 16 years or more with acute encephalitis from 2001
      to 2005 was undertaken in 2006. RESULTS: During the study period, 49 patients
      were diagnosed with acute encephalitis. The subtype of acute encephalitis was as
      follows: 10 patients with herpes simplex encephalitis (HSE), 12 patients with
      NHALE, 4 patients with paraneoplastic encephalitis, 2 patients with encephalitis
      associated with collagen disease, one patient with viral encephalitis other than
      HSE, 20 patients with encephalitis with unknown causes. The service-based
      incidence rate of acute encephalitis was 19.0 per million person-years. The
      incidence rate of NHALE subtype was 4.7 per million person-years. CONCLUSIONS:
      Our epidemiological survey indicated an estimated 550 patients would develop
      NHALE per year in Japan, suggesting that NHALE may not be a rare disorder.

PMID- 18717728
TI  - Clinical heterogeneity and genotype-phenotype correlations in hereditary spastic
      paraplegia because of Spatacsin mutations (SPG11).
AB  - BACKGROUND: Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin
      corpus callosum is a distinct and usually severe form of complex hereditary
      spastic paraplegia classified as SPG11. Recently mutations on SPG11 gene
      (KIAA1840), which is localized to chromosome 15q13-q15, were shown to cause the
      majority of SPG11 cases. METHODS: We analysed the 40 coding exons of this gene in
      the probands from eight families with complex ARHSP, four of these families had a
      thin corpus callosum and two has mild thinning. RESULTS: Three families were
      identified with novel mutations in the SPG11 gene. One family was of Asian origin
      with a homozygous nonsense mutation and had a very severe phenotype but only very
      mild thinning of the corpus callosum. In the other two English families the
      parents were unrelated and the mutations were compound heterozygotes. In these
      two families the phenotype was mild and both probands had a thin corpus callosum.
      CONCLUSION: Given the probable mechanism of action of the mutations in the
      Spatacsin gene, we discuss the probable genotype phenotype correlations in these
      families. This study confirms the frequent occurrence of Spatacsin mutations in
      complex ARHSP with genotype phenotype effects and exposes the spectrum of
      clinical heterogeneity in SPG11.

PMID- 18717729
TI  - A 1H magnetic resonance spectroscopy study in patients with obstructive sleep
      apnea.
AB  - BACKGROUND AND PURPOSE: Repeated episodes of hypoxia, hypercapnia and transient
      blood pressure elevation in obstructive sleep apnea syndrome (OSAS) may damage
      neutral structures and induce cerebral metabolic impairment. This study aimed to
      determine the impact of OSAS on cerebral metabolites measured by (1)H magnetic
      resonance spectroscopy ((1)H -MRS). METHODS: Twenty OSAS patients underwent
      standard overnight polysomnography and (1)H-MRS separately. Proton volumes of
      interest (VOIs) were placed in frontal and midtemporal regions bilaterally.
      RESULTS: Significantly lower values of the N-acetylaspartate (NAA)/creatine (Cr)
      ratio were found in frontal regions (P < 0.004) compared with 20 age-matched
      control subjects. A significant increase in the myo-inositol (Ins)/Cr ratio was
      evident bilaterally in temporal and frontal regions (P < 0.00002 and P < 0.04).
      Choline (Cho)/Cr ratio values were also significantly greater in temporal regions
      (P < 0.00001). A significant negative correlation (r = -0.51, P < 0.03) was found
      between the apnea-hypopnea index (AHI) and NAA/Cr ratio in the frontal regions of
      OSAS patients. CONCLUSIONS: Reduction in the NAA/Cr ratio in frontal regions of
      OSAS patients could be related to neural loss. Increase in the Cho/Cr ratio in
      temporal regions and Ins/Cr ratio in both frontal and temporal regions could be
      interpreted as evidence of membrane breakdown and reactive gliosis, respectively,
      consequent to repeated episodes of hypoxia in OSAS.

PMID- 18717730
TI  - Diagnostic value of brain MRI and 18F-FDG PET in the differentiation of
      Parkinsonian-type multiple system atrophy from Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Differentiation between parkinsonian type multiple system
      atrophy (MSA-P) and Parkinson's disease (PD) is important but often difficult. We
      investigated the diagnostic value of brain magnetic resonance imaging (MRI) and
      (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in
      differentiating MSA-P from PD. METHODS: Twenty-four patients with MSA-P (16
      probable and 8 possible) and eight patients with PD were included in this study.
      RESULTS: For analysis using the putaminal findings, the sensitivities were 58.3%
      by visual analysis of brain MRI, 95.8% by visual analysis of (18)F-FDG PET, and
      79.2% by statistical parametric mapping (SPM) analysis of (18)F-FDG PET in
      differentiating MSA-P from PD; the specificity was 100% for each analysis. Using
      the putaminal findings, visual analysis of (18)F-FDG PET had a higher sensitivity
      compared with brain MRI (P = 0.004) and SPM analysis of (18)F-FDG PET revealed a
      tendency towards higher sensitivity compared with brain MRI (P = 0.063). For
      analysis using both putaminal and infratentorial findings, the sensitivities were
      79.2% by visual analysis of brain MRI, 95.8% by visual analysis of (18)F-FDG PET,
      95.8% by SPM analysis of (18)F-FDG PET in differentiating MSA-P from PD; the
      specificity was 100% for each analysis. CONCLUSION: Both brain MRI and (18)F-FDG
      PET showed diagnostic usefulness in differentiating MSA-P from PD, with (18)F-FDG
      PET being more sensitive than brain MRI.

PMID- 18717731
TI  - Mapping immediate-early gene activity in the rat after place learning in a water
      maze: the importance of matched control conditions.
AB  - The expression of two immediate-early genes (IEGs), Zif268 and c-Fos, was
      quantified in hippocampal subregions and related structures following spatial
      learning in the Morris water-maze. A critical feature was the novel control
      protocol alongside more standard controls, the purpose of which was to test
      whether hippocampal activity is set automatically when traversing an environment
      or whether it is dependent on reaching a specific goal using learning that
      requires the hippocampus (i.e. task dependent). The new control protocol
      (Procedural Task) made it possible to match swim time, swim distance and learning
      to escape from water with that of the experimental (Working Memory) group. Unlike
      the Working Memory group, the Procedural Task animals showed no evidence of
      learning the absolute platform location during the test session. While the
      Working Memory rats showed c-Fos increases relative to the Procedural Task
      controls in the frontal and parahippocampal cortices, hippocampal levels did not
      differ. Again, for Zif268 there was no evidence of a relative increase of
      hippocampal activity in the Working Memory group. In fact, hippocampal Zif268
      showed evidence of a relative decrease, even though the spatial working memory
      task is hippocampal dependent. The study not only highlighted the shortcomings of
      other control procedures used in water-maze studies (free-swimming or home cage
      control), but also indicated that the expression of these IEGs in the hippocampus
      is not a direct predictor of explicit spatial location learning. Rather, the
      activity in combinations of regions, including prefrontal cortex, provides a
      stronger correlate of water-maze learning.

PMID- 18717732
TI  - Transient middle cerebral artery occlusion disrupts the forelimb movement
      representations of rat motor cortex.
AB  - Infarcts from proximal middle cerebral artery (MCA) stroke can produce
      impairments in motor function, particularly finger movements in humans and digit
      flexion in rats. In rats, the extent of neural damage may be limited to basal
      ganglia structures or may also include portions of the frontal and parietal
      cortex in severe cases. Although the primary motor cortex (M1) is anatomically
      spared in proximal MCA occlusion, its functional integrity is suspect because
      even a small subcortical infarct can damage neural circuits linking M1 with basal
      ganglia, brainstem, and spinal cord. This motivated the present study to
      investigate the neurophysiological integrity of M1 after transient proximal MCA
      occlusion. Rats, preoperatively trained and non-preoperatively trained to reach
      for food, received extensive reach training/testing with the contralateral-to
      lesion paw for several weeks after MCA occlusion. The forelimb movement
      representations were assayed from the ipsilateral-to-lesion M1 with intracortical
      microstimulation approximately 10 weeks after MCA occlusion. Digit flexion was
      impaired during food grasping in rats with relatively small subcortical infarcts
      and was completely abolished in rats that sustained at least moderate subcortical
      damage. Corresponding forelimb movement representations ranged from abnormally
      small to absent. The results suggest that ischemia in subcortical territories of
      the MCA does not spare the neurophysiological properties of M1 despite its
      apparent anatomical intactness, probably because of damage sustained to its
      descending fibers. Thus, M1 dysfunction contributes to the impairments that ensue
      from proximal MCA occlusion, even when the infarct is limited to subcortical
      regions.

PMID- 18717733
TI  - Activity requires soluble amyloid precursor protein alpha to promote neurite
      outgrowth in neural stem cell-derived neurons via activation of the MAPK pathway.
AB  - It is known that activity modulates neuronal differentiation in the adult brain
      but the signalling mechanisms underlying this process remain to be identified. We
      show here that activity requires soluble amyloid precursor protein (sAPP) to
      enhance neurite outgrowth of young neurons differentiating from neural stem
      cells. Inhibition of sAPP secretion and anti-APP antibodies both abolished the
      effect of depolarization on neurite outgrowth, whereas exogenous sAPPalpha,
      similar to depolarization, induced neurite elongation. Depolarization and
      sAPPalpha both required active N-methyl-D-aspartic acid receptor (NMDAR) and
      mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase
      (ERK) recruitment to induce neurite outgrowth. However, depolarization and
      sAPPalpha played different roles in modulating this signalling cascade.
      Depolarization induced ERK phosphorylation with fast kinetics via activation of
      NMDAR. By contrast, acute application of sAPPalpha did not lead to ERK
      activation. However, continuous generation of sAPPalpha was necessary for
      depolarization-induced ERK phosphorylation, indicating that sAPPalpha promotes
      MAPK/ERK recruitment by an indirect mechanism. In addition, we found that
      blockade of NMDAR down-regulated APP expression, whereas depolarization increased
      sAPPalpha, suggesting that activity may also act upstream of sAPP signalling by
      regulating the amount of cellular APP and extracellular sAPPalpha. Finally, we
      show that soluble amyloid precursor-like protein 2 (sAPLP2), but not sAPLP1, is
      functionally redundant to sAPP in promoting neurite outgrowth and that soluble
      members of the APP family require membrane-bound APP to enhance neurite
      outgrowth. In summary, these experiments indicate a novel role of APP family
      members in activity-dependent neuronal differentiation.

PMID- 18717734
TI  - The p75 neurotrophin receptor regulates hippocampal neurogenesis and related
      behaviours.
AB  - Although changes to neural circuitry are believed to underlie behavioural
      characteristics mediated by the hippocampus, the contribution of neurogenesis to
      this process remains controversial. This is partially because the molecular
      regulators of neurogenesis remain to be fully elucidated, and experiments
      generically preventing neurogenesis have, for the most part, depended on
      paradigms involving irradiation. Here we show that mice lacking the p75
      neurotrophin receptor (p75(NTR-/-)) have 25% fewer neuroblasts and 50% fewer
      newborn neurons in the dentate gyrus, coincident with increased rates of cell
      death of newly born cells and a significantly smaller granular cell layer and
      dentate gyrus, than those of p75(NTR+/+) mice. Whereas p75(NTR-/-) mice had
      increased latency to feed in a novelty-suppressed feeding paradigm they had
      increased mobility in another test of "depression", the tail-suspension test.
      p75(NTR-/-) mice also had subtle behavioural impairment in Morris water maze
      tasks compared to wild-type animals. No difference between genotypes was found in
      relation to anxiety or exploration behaviour based on the elevated-plus maze,
      light-dark, hole-board, T-maze or forced-swim tests. Overall, this study
      demonstrates that p75(NTR) is an important regulator of hippocampal neurogenesis,
      with concomitant effects on associated behaviours. However, the behavioural
      attributes of the p75(NTR-/-) mice may be better explained by altered circuitry
      driven by the loss of p75(NTR) in the basal forebrain, rather than direct changes
      to neurogenesis.

PMID- 18717735
TI  - Lowered cAMP and cGMP signalling in the brain during levodopa-induced dyskinesias
      in hemiparkinsonian rats: new aspects in the pathogenetic mechanisms.
AB  - Dysregulation of dopamine receptors is thought to underlie levodopa-induced
      dyskinesias in experimental models of Parkinson's disease. It is unknown whether
      an imbalance of the second messengers, cyclic adenosine monophosphate (cAMP) and
      cyclic guanosine monophosphate (cGMP), is involved in the alterations of
      levodopa/dopamine signal transduction. We examined cAMP and cGMP signalling in
      the interconnected cortico-striatal-pallidal loop at the peak of levodopa-induced
      dyskinesias in rats with 6-hydroxydopamine lesions in the substantia nigra. In
      addition, we examined the role of phosphodiesterase (PDE) and the rate of cAMP
      and cGMP degradation on the severity of levodopa-induced dyskinesias in animals
      pretreated with PDE inhibitor, zaprinast. Unilateral lesion of substantia nigra
      led to an increase in cAMP but a decrease in cGMP levels in the ipsilateral basal
      ganglia. After chronic levodopa treatment, cAMP and cGMP were differentially
      regulated in eukinetic animals: the cAMP level increased in the cortex and
      striatum but decreased in the globus pallidus of both hemispheres, whereas the
      cGMP decreased below baseline levels in the contralateral cortico-striatal
      pallidal regions. In dyskinetic animals chronic levodopa treatment led to an
      absolute decrease in cAMP and cGMP levels in cortico-striatal-pallidal regions of
      both hemispheres. Pretreatment with zaprinast reduced the severity of levodopa
      induced dyskinesias, and partly prevented the decrease in cyclic nucleotides
      compared with pretreatment with saline-levodopa. In conclusion, using a rat model
      of hemiparkinsonism, we observed a significant reduction in the levels of cyclic
      nucleotides in both hemispheres at the peak of levodopa-induced dyskinesias. We
      propose that such a decrease in cyclic nucleotides may partly result from
      increased catabolism through PDE overactivity.

PMID- 18717736
TI  - Involvement of glypican-1 autoprocessing in scrapie infection.
AB  - The copper-binding cellular prion protein (PrP(C)) and the heparan sulphate (HS)
      containing proteoglycan glypican-1 (Gpc-1) can both be attached to lipid rafts
      via their glycosylphosphatidylinositol anchors, and copper ions stimulate their
      cointernalization from the cell surface to endosomes. The prion protein controls
      cointernalization and delivers copper necessary for S-nitrosylation of conserved
      cysteines in the Gpc-1 core protein. Later, during recycling through endosomal
      compartments, nitric oxide can be released from the S-nitroso groups and
      catalyses deaminative degradation and release of the HS substituents. Here, by
      using confocal immunofluorescence microscopy, we show that normal PrP(C) and Gpc
      1 colocalize inside GT1-1 cells. However, in scrapie-infected cells (ScGT1-1),
      Gpc-1 protein remained at the cell surface separate from the cellular prion
      protein. Scrapie infection stimulated Gpc-1 autoprocessing and the generated HS
      degradation products colocalized with intracellular aggregates of the disease
      related scrapie prion protein isoform (PrP(Sc)). Coimmunoprecipitation
      experiments demonstrated an association between Gpc-1 and PrP(C) in uninfected
      cells, and between HS degradation products and PrP(Sc) in infected cells.
      Silencing of Gpc-1 expression or prevention of Gpc-1 autoprocessing elevated the
      levels of intracellular PrP(Sc) aggregates in infected cells. These results
      suggest a role for Gpc-1 autoprocessing in the clearance of PrP(Sc) from infected
      cells.

PMID- 18717737
TI  - Neurophysiological signature of effective anticipatory task-set control: a task
      switching investigation.
AB  - Changing between cognitive tasks requires a reorganization of cognitive
      processes. Behavioural evidence suggests this can occur in advance of the
      stimulus. However, the existence or detectability of an anticipatory task-set
      reconfiguration process remains controversial, in part because several
      neuroimaging studies have not detected extra brain activity during preparation
      for a task switch relative to a task repeat. In contrast, electrophysiological
      studies have identified potential correlates of preparation for a task switch,
      but their interpretation is hindered by the scarcity of evidence on their
      relationship to performance. We aimed to: (i) identify the brain potential(s)
      reflecting effective preparation for a task-switch in a task-cuing paradigm that
      shows clear behavioural evidence for advance preparation, and (ii) characterize
      this activity by means of temporal segmentation and source analysis. Our results
      show that when advance preparation was effective (as indicated by fast
      responses), a protracted switch-related component, manifesting itself as
      widespread posterior positivity and concurrent right anterior negativity,
      preceded stimulus onset for approximately 300 ms, with sources primarily in the
      left lateral frontal, right inferior frontal and temporal cortices. When advance
      preparation was ineffective (as implied by slow responses), or made impossible by
      a short cue-stimulus interval (CSI), a similar component, with lateral prefrontal
      generators, peaked approximately 300 ms poststimulus. The protracted prestimulus
      component (which we show to be distinct from P3 or contingent negative variation,
      CNV) also correlated over subjects with a behavioural measure of preparation.
      Furthermore, its differential lateralization for word and picture cues was
      consistent with a role for verbal self-instruction in preparatory task-set
      reconfiguration.

PMID- 18717738
TI  - Novel autotrophic arsenite-oxidizing bacteria isolated from soil and sediments.
AB  - Arsenic oxidation is recognized as being mediated by both heterotrophic and
      chemoautotrophic microorganisms. Enrichment cultures were established to
      determine whether chemoautotrophic microorganisms capable of oxidizing arsenite
      As(III) to arsenate As(V) are present in selected contaminated but nonextreme
      environments. Three new organisms, designated as strains OL-1, S-1 and CL-3, were
      isolated and found to oxidize 10 mM arsenite to arsenate under aerobic conditions
      using CO2-bicarbonate (CO2/HCO3-) as a carbon source. Based on 16S rRNA gene
      sequence analyses, strain OL-1 was 99% most closely related to the genus
      Ancylobacter, strain S-1 was 99% related to Thiobacillus and strain CL-3 was 98%
      related to the genus Hydrogenophaga. The isolates are facultative autotrophs and
      growth of isolated strains on different inorganic electron donors other than
      arsenite showed that all three had a strong preference for several sulfur
      species, while CL-3 was also able to grow on ammonium and nitrite. The RuBisCO
      Type I (cbbL) gene was positively amplified and sequenced in strain CL-3, and the
      Type II (cbbM) gene was detected in strains OL-1 and S-1, supporting the
      autotrophic nature of the organisms.

PMID- 18717739
TI  - Lack of anti-inflammatory effect of botulinum toxin type A in experimental models
      of inflammation.
AB  - Botulinum toxin type A (BTX-A) has a long-lasting antinociceptive activity and
      less clear effect on inflammation. It was proposed that these two effects share
      the same mechanism--the inhibition of neurotransmitter exocytosis from peripheral
      nerve endings. However, till now possible anti-inflammatory action of BTX-A did
      not evoke much attention. In the present paper, we investigate possible anti
      inflammatory action of the toxin in carrageenan and capsaicin models of
      inflammation in rats. BTX-A (5 and 10 U/kg) was injected into the plantar surface
      of the rat right hind-paw pad 5 days before the injection of the carrageenan (1%)
      or capsaicin (0.1%) at the same site. Carrageenan-induced paw oedema and
      capsaicin-induced protein extravasation were measured. Control, inflamed and BTX
      A pretreated inflamed paws were photographed and histopathological analysis
      (haematoxylin & eosin) was performed. Pretreatment with BTX-A had no effect on
      the size of carrageenan-induced paw oedema, measured as paw volume and weight or
      capsaicin-induced plasma extravasations, measured by Evans blue as a marker of
      protein leakage. Neither macroscopic nor microscopic analysis showed a
      significant difference between BTX-A pretreated and control inflamed tissue.
      Results show dissociation between the effect of BTX-A on pain and inflammation
      thus questioning the validity of the suggested assumption about the common
      peripheral mechanism of action.

PMID- 18717740
TI  - von Willebrand factor content in Alphanate.

PMID- 18717741
TI  - Flower power: tree flowering phenology as a settlement cue for migrating birds.
AB  - 1. Neotropical migrant birds show a clear preference for stopover habitats with
      ample food supplies; yet, the proximate cues underlying these decisions remain
      unclear. 2. For insectivorous migrants, cues associated with vegetative phenology
      (e.g. flowering, leaf flush, and leaf loss) may reliably predict the availability
      of herbivorous arthropods. Here we examined whether migrants use the phenology of
      five tree species to choose stopover locations, and whether phenology accurately
      predicts food availability. 3. Using a combination of experimental and
      observational evidence, we show migrant populations closely track tree phenology,
      particularly the flowering phenology of honey mesquite (Prosopis glandulosa), and
      preferentially forage in trees with more flowers. Furthermore, the flowering
      phenology of honey mesquite reliably predicts overall arthropod abundance as well
      as the arthropods preferred by migrants for food. 4. Together, these results
      suggest that honey mesquite flowering phenology is an important cue used by
      migrants to assess food availability quickly and reliably, while in transit
      during spring migration.

PMID- 18717742
TI  - The consistency and stability of abundance-occupancy relationships in large-scale
      population dynamics.
AB  - 1. Abundance-occupancy relationships comprise some of the most general and well
      explored patterns in macro-ecology. The theory governing these relationships
      predicts that species will exhibit a positive interspecific and intraspecific
      relationship between regional occupancy and local abundance. Abundance-occupancy
      relationships have important implications in using distributional surveys, such
      as atlases, to understand and document large-scale population dynamics and the
      consequences of environmental change. A basic need for interpreting such data
      bases is a better understanding of whether changes in regional occupancy reflect
      changes in local abundance across species of varying life-history
      characteristics. 2. Our objective was to test the predictions of the abundance
      occupancy rule using two independent data sets, the New York State Breeding Bird
      Atlas and the North American Breeding Bird Survey. The New York State Breeding
      Bird Atlas consists of 5332 25-km(2) survey blocks and is one of the first
      atlases in the USA to be completed for two time periods (1980-85 and 2000-05).
      The North American Breeding Survey is a large-scale annual survey intended to
      document the relative abundance and population change of songbirds throughout the
      USA. 3. We found that regional occupancy was positively correlated with relative
      abundance across 98 (beta = 0.60 +/- 0.11 SE, P < 0.001, R(2) = 0.60) and 85
      species (beta = 0.67 +/- 0.06 SE, P < 0.001, R(2) = 0.57) in two separate time
      periods. This relationship proved stable over time and was notably consistent
      between breeding habitat groups and migratory guilds. 4. Between 1980 and 2005,
      changes in regional occupancy were highly correlated with long-term abundance
      trend estimates for 75 species (beta = 5.73 +/- 0.24 SE, P < 0.001, R(2) = 0.88).
      Over a 20-year period, woodland and resident birds showed an increase in
      occupancy while grassland species showed the greatest decline; these patterns
      were mirrored by changes in local abundance. 5. Although exceptions existed, we
      found most changes in occupancy parallel changes in local abundance. These
      findings support the basic predictions of the abundance-occupancy rule and
      demonstrate its consistency and stability in species and groups of varying life
      history characteristics.

PMID- 18717743
TI  - How is research evidence used to support claims made in advertisements for wound
      care products?
AB  - AIMS AND OBJECTIVE: To investigate the amount, type and accuracy of citations use
      in support of product related claims from advertisements of wound care products.
      BACKGROUND: Although articles submitted to most medical journals are subjected to
      peer review, such scrutiny is often not required for the content of
      advertisements. DESIGN: A contents survey of advertisements from two wound care
      journals (Journal of Wound Care and Ostomy Wound Management) from 2002-2003 and
      the British Medical Journal, 2002-2003. METHODS: Data collected from
      advertisements included identification of product related claims made and any
      corresponding citations. Where journal articles were cited to support claims, the
      articles were obtained. Where data on file were cited, this material was
      requested. In each case the accuracy of claims in relation to the content of the
      supporting citation was assessed. RESULTS: The use of citations to support
      product related claims was infrequent in advertisements from wound care journals,
      where 35% of advertisements containing a product related claim also contained at
      least one citation, compared with 63% of advertisements from the British Medical
      Journal. Of citations that were supplied, journal articles were less common in
      the wound journals (40% vs. 73% in the British Medical Journal) and data on file
      more common (38% vs. 6% in the British Medical Journal). Where journal articles
      were obtained, 56% of claims in the wound care journals advertisements were not
      supported by the cited article, compared with 12% of claims in the British
      Medical Journal. CONCLUSION: The wound journals advertised predominantly medical
      devices. The use and accuracy of referencing in advertisements from wound care
      journals was poor. RELEVANCE TO CLINICAL PRACTICE: Nurses have increasing
      responsibilities for the prescribing of both drugs and devices, which must be
      accompanied by the ability to interpret marketing materials and research evidence
      critically. Nurse educators must ensure that nurse education generally and nurse
      prescriber training particularly, builds skills of information retrieval and
      critical appraisal.

PMID- 18717744
TI  - 308-nm excimer laser in psoriasis vulgaris, scalp psoriasis, and palmoplantar
      psoriasis.
AB  - BACKGROUND: The 308-nm excimer laser is a recent development in the treatment of
      psoriasis vulgaris, palmoplantar psoriasis, and psoriasis of the scalp. The XeCl
      excimer emits a 308-nm wavelength beam of light that is monochromatic and
      coherent. These properties allow selectivity when used as phototherapy against a
      psoriatic lesion while sparing healthy surrounding tissue. OBJECTIVE: In this
      manuscript, we review recent updates on the efficacy of excimer and its most
      recent trials in psoriasis. METHODS: A review of the medical literature in Pubmed
      database was performed using the terms 'psoriasis' and '308 nm excimer laser'.
      All trials to date that studied the 308-nm excimer including those that compared
      the excimer with other modalities were included. RESULTS: Eighteen trials show
      positive results surrounding the efficacy of the excimer. Selectivity of the 308
      nm excimer, when compared with non-selective narrowband UVB (NB-UVB) phototherapy
      allows one to adjust the fluency to the lesion. The excimer may also stand
      superior to NB-UVB in its efficacy of mechanism. CONCLUSION: Excimer is a useful
      and effective treatment for psoriasis that may be used as a compliment to topical
      medications as well as NB-UVB. However, large randomized trials with long-term
      follow-up are needed to further support this.

PMID- 18717745
TI  - A recurrent keratin 14 mutation in Dowling-Meara epidermolysis bullosa simplex in
      a Chinese family.

PMID- 18717746
TI  - No resistance to male-killing Wolbachia after thousands of years of infection.
AB  - Maternally transmitted male-killing endosymbionts can exert strong and relentless
      selection pressure on their hosts to evolve resistance to these infections.
      Surveys of current infection prevalence and mtDNA diversity indicate that
      Drosophila innubila is and has been infected with male-killing Wolbachia at
      moderate frequencies for extended evolutionary periods. Here, we use coalescent
      simulations to infer the minimum age of the Wolbachia infection in this species,
      and estimate that the infection is at least 15,000 and perhaps over 700,000 years
      old. We also surveyed this species for genetic variation for resistance to the
      male-killing effects of infection. Our surveys revealed no evidence for any
      resistance polymorphism, such that all flies are completely susceptible to male
      killing. Given the general assumption that Drosophila can be selected for
      anything, the lack of resistance, despite thousands of years of strong selection,
      is an apparent evolutionary conundrum. We hypothesize that resistance requires a
      mutation of major effect that acts early in development, and that the adverse
      pleiotropic consequences of such mutations in both infected and uninfected
      individuals may exceed the possible benefit to infected flies.

PMID- 18717747
TI  - Adaptive eukaryote-to-eukaryote lateral gene transfer: stress-related genes of
      algal origin in the closest unicellular relatives of animals.
AB  - In addition to mutation, gene duplication and recombination, the transfer of
      genetic material between unrelated species is now regarded as a potentially
      significant player in the shaping of extant genomes and the evolution and
      diversification of life. Although this is probably true for prokaryotes, the
      extent of such genetic exchanges in eukaryotes (especially eukaryote-to-eukaryote
      transfers) is more controversial and the selective advantage and evolutionary
      impact of such events are less documented. A laterally transferred gene could
      either be added to the gene complement of the recipient or replace the
      recipient's homologue; whereas gene replacements can be either adaptive or
      stochastic, gene additions are most likely adaptive. Here, we report the finding
      of four stress-related genes (two ascorbate peroxidase and two metacaspase genes)
      of algal origin in the closest unicellular relatives of animals, the
      choanoflagellates. At least three of these sequences represent additions to the
      choanoflagellate gene complement, which is consistent with these transfers being
      adaptive. We suggest that these laterally acquired sequences could have provided
      the primitive choanoflagellates with additional or more efficient means to cope
      with stress, especially in relation to adapting to freshwater environments and/or
      sessile or colonial lifestyles.

PMID- 18717748
TI  - Maximized virulence in a sterilizing pathogen: the anther-smut fungus and its co
      evolved hosts.
AB  - Host sterilization is a common feature of sexually transmitted diseases (STDs).
      Because host reproductive failure may free up resources for pathogen reproduction
      and transmission, theory predicts that selection on sterilizing pathogens will
      favour maximum virulence (i.e. complete sterilization). We examined patterns of
      infection in sexually transmitted anther-smut fungi (Microbotryum) on four of
      their host species in the Caryophyllaceae. Using controlled fungal matings and
      experimental inoculations, we compared disease expression in inoculations ranging
      from host-specific pathogens to hybrids and cross-species treatments. Our data
      support the existence of host-specific sibling species within the genus
      Microbotryum based on a low infection rate from cross-inoculations and reduced
      fitness for hybrid pathogens. These patterns of host specificity and reproductive
      isolation, however, were not absolute. We did observe some successful cross
      species and hybrid infections, but the expression of disease was frequently
      incomplete, including only partial host sterilization and the failed dehiscence
      of pathogen spores. The prevalence of these maladapted disease phenotypes may
      greatly inhibit the emergence of novel host pathogen combinations. Infections by
      hybrid pathogen genotypes were intermediate, in terms of both infection rate and
      the normality of disease symptoms, between host-specific and cross-inoculated
      pathogens. In addition, the frequency with which hybrid and cross-inoculated
      anther-smut pathogens were able to infect but not sterilize new hosts supports
      the prediction that sterilizing STDs are under selection to maximize virulence in
      natural populations.

PMID- 18717749
TI  - Host-parasite coevolution and patterns of adaptation across time and space.
AB  - The description of coevolutionary dynamics requires a characterization of the
      evolutionary dynamics of both the parasite and its host. However, a thorough
      description of the underlying genetics of the coevolutionary process is often
      extremely difficult to carry out. We propose that measures of adaptation (mean
      population fitness) across time or space may represent a feasible alternative
      approach for characterizing important features of the coevolutionary process. We
      discuss recent experimental work in the light of simple mathematical models of
      coevolution to demonstrate the potential power of this phenotypic experimental
      approach.

PMID- 18717750
TI  - Divergent timing of egg-laying may maintain life history polymorphism in
      potentially multivoltine insects in seasonal environments.
AB  - The length of the favourable season determines voltinism in insect populations.
      In some insects, there is variation in fecundity and timing of reproduction among
      females. If the length of the favourable season does not allow all offspring to
      develop into adults without diapause, the benefits of high early fecundity may
      outweigh the associated cost of low lifetime fecundity. We tested this by
      exploring mating frequencies of Pieris napi females along a latitudinal gradient
      in different generations. Pieris napi is a bivoltine butterfly, and genetically
      polyandrous females enjoy higher lifetime fecundity than monandrous ones.
      Polyandry is, however, coupled with a relatively low early fecundity. We found
      that monandrous females are more likely to produce an additional generation than
      polyandrous ones under conditions that allow production of only a partial summer
      generation. Monandrous females were also the first to emerge and slightly over
      represented in the summer generation under conditions that allow the development
      of a complete summer generation. Further, a stochastic model shows that variation
      in the timing of reproduction between strategies is sufficient to explain the
      observed patterns. Thus, seasonality may counter-select against polyandry, or
      more generally against low early reproductive rate, and promote maintenance of
      polymorphism in life history strategies.

PMID- 18717751
TI  - Analysis of suspected trace human remains from an indoor concrete surface.
AB  - This paper describes the sequence of analyses used to determine the nature of a
      stain located on the floor of room in the former Athens Mental Health and
      Retardation Hospital in Athens, OH. The location of the stain was reported to be
      the position in which a decomposing body was discovered on January 11, 1979. The
      current stain is found to contain strong evidence for both natural decomposition
      products and deliberate adulteration. Microscopic analyses, solubility tests,
      FTIR, ICP-OES, pyrolysis-MS, and derivatization GC-MS were consistent in
      determining the removable parts of the stain to be composed mostly of calcium and
      sodium salts of free fatty acids, such as palmitic acid, consistent with previous
      descriptions of adipocere. The free fatty acids could have been formed via known
      bacterial degradation pathways or via saponification through the basic
      environment caused through contact with the concrete. To our knowledge, adipocere
      formation on an exposed indoor environment has not been described before. The
      stain and concrete also show signs of being chemically modified with an acidic
      reagent, such as Blu-Lite--a phosphoric acid-based cleaner that was a commonly
      used cleaner in the building from the time of discovery to the present day. The
      chemical etching appears to have been restricted to an area resembling the shape
      of a human body, which is consistent with deliberate adulteration of the
      appearance of the stain.

PMID- 18717752
TI  - The thermodynamics of latent fingerprint corrosion of metal elements and alloys.
AB  - Redox reactions taking place between the surface of a metal and fingerprint
      residue have been expressed thermodynamically in terms of both the Nernst
      equation for reduction potential and the complexation constant for the formation
      of complex metal halide ions in aqueous solution. These expressions are used to
      explain experimental results for the corrosion of 10 different metal elements by
      fingerprint residue in air at room temperature. Corrosion of noble metals, such
      as silver and gold, supports the proposition that the degree of metal corrosion
      is enhanced by the presence of chloride ions in eccrine sweat. Extending the
      experiments to include 10 metal alloys enabled the construction of a fingerprint
      corrosion series for 20 different metals. Fingerprint corrosion on metals alloyed
      with > approximately 40% copper was found to display third level fingerprint
      detail. A comparison of both conventional ink on paper and digital (Livescan)
      fingerprinting techniques with fingerprints deposited on 9 Karat gold alloy has
      shown that gold alloy depositions are least susceptible to third level detail
      obliteration by poor fingerprint capturing techniques.

PMID- 18717753
TI  - Age-related factors in the relationship between foot measurements and living
      stature and body weight.
AB  - The measurements of feet and footprints are especially important in forensic
      identification, as they have been used to predict the body height and weight of
      victims or suspects. It can be observed that the subjects of forensic-oriented
      studies are generally young adults. That is to say, researchers rarely take into
      consideration the body's proportional changes with age. Hence, the aim of this
      study is to generate equations which take age and sex into consideration, when
      stature and body weight are estimated from foot and footprints dimensions. With
      this aim in mind, we measured the stature, body weight, foot length and breadth,
      heel breadth, footprint length and breadth, and footprint heel breadth of 516
      volunteers (253 males and 263 females) aged between 17.6 and 82.9 years using
      standard measurement techniques. The sample population was divided randomly into
      two groups. Group 1, the study group, consisted of 80% of the sample (n = 406);
      the remaining 20% were assigned to the cross-validation group or Group 2 (n =
      110). In the first stage of the study, we produced equations for estimating
      stature and weight using a stepwise regression technique. Then, their reliability
      was tested on Group 2 members. Statistical analyses showed that the ratios of
      foot dimensions to stature and body weight change considerably with age and sex.
      Consequently, the regression equations which include these variables yielded more
      reliable results. Our results indicated that age and sex should be taken into
      consideration when predicting human body height and weight for forensic purposes.

PMID- 18717754
TI  - A metric method for sex determination using the proximal femur and fragmentary
      hipbone.
AB  - The pubic bone is considered one of the best sources of information for
      determining sex using skeletal remains, but can be easily damaged postmortem.
      This problem has led to the development of nonpelvic methods for cases when the
      pubic bone is too damaged for analysis. We approached this problem from a
      different perspective. In this article, we present an approach using new
      measurements and angles of the proximal femur to recreate the variation in the
      pubic bone. With a sample from the Terry Collection (n > 300), we use these new
      variables along with other traditional measurements of the femur and hipbone to
      develop two logistic regression equations (femur and fragmentary hipbone, and
      femur only) that are not population specific. Tests on an independent sample
      (Grant Collection; n = 37-40) with a different pattern of sexual dimorphism
      resulted in an allocation accuracy of 95-97% with minimal difference by sex.

PMID- 18717755
TI  - Frontal sinus accuracy in identification as measured by false positives in kin
      groups.
AB  - The aims of this study were to verify if frontal sinuses can uniquely identify
      individuals belonging to family groups using Cameriere methods and to test if
      kinship can affect the proportion of erroneous identifications. For this purpose,
      we compared the proportion of false-positive identifications in a sample of 99
      individuals within 20 families with a control sample of 98 other individuals
      without kinship. The results show that the combined use of SOR and the Yoshino
      code number allows personal identification with a small probability of false
      positives (p < 10(-6)), even when kinship is taken into account. The present
      research confirms the importance of studying anthropological frameworks for
      identification, which leads to reliable methods and allows for both quick and
      economic procedures.

PMID- 18717756
TI  - Case-crossover study of hospitalization for acute hepatitis in Chinese herb
      users.
AB  - BACKGROUND AND AIM: Despite the increase in popularity of herbal products, there
      is growing concern over potential health hazards caused by the Chinese herbal
      medicines (CHMs) that are regularly reimbursed under the National Health
      Insurance system in Taiwan. This study attempts to determine the association
      between CHM prescriptions and acute hepatitis-related hospitalizations. METHODS:
      A case-crossover study was designed on 200,000 randomly selected individuals from
      the National Health Insurance Research Database who were then followed from 1997
      to 2002. All medications taken in the 30- and 60-day periods prior to
      hospitalization were explored and compared with four control periods (the 180-
      and 360-day periods prior to and after the hospitalization). A conditional
      logistic regression model was then constructed to determine the odds of CHM being
      prescribed during these risk periods. RESULTS: There were a total of 12 cases
      with nonviral, nonalcoholic hepatitis patients who took CHM prescriptions during
      the 30-day risk or control periods. After adjustment for conventional hepatotoxic
      drugs, the odds ratio during the 30-day risk period was 3.4 (95% confidence
      interval [CI]: 1.1, 9.8) for nonviral, nonalcoholic acute hepatitis. A detailed
      historical review of CHMs for each patient revealed that the odds ratio increased
      to 4.2 for those prescribed formulae containing Radix Paeoniae (95% CI: 1.1,
      15.7) and Radix Glycyrrhizae (95% CI: 1.2, 15.2). CONCLUSIONS: Chinese herbal
      users revealed a slightly increased risk of acute hepatitis. We therefore
      recommend pharmacovigilance and active surveillance for CHMs suspected with
      hepatotoxicity.

PMID- 18717757
TI  - Natural history of hepatitis B virus-related cirrhotic patients hospitalized to
      control ascites.
AB  - BACKGROUND AND AIM: Few studies have assessed the natural history of hepatitis B
      virus (HBV)-related cirrhotic ascites. We investigated the natural history of
      patients with HBV-related cirrhotic ascites hospitalized to control ascites and
      determined their prognosis, including survival rates and prognostic factors
      affecting survival. METHODS: Between January 1996 and December 2005, 203
      consecutive patients with HBV-related cirrhotic ascites were followed for a
      median of 80.7 months (range, 15-149) after their first significant ascitic
      decompensation that required hospitalization. RESULTS: The mean age of all
      patients was 52.6 years. Male gender predominated (male/female, 138/65). A
      subgroup analysis of 165 patients who had ascitic decompensation as their first
      episode of hepatic decompensation revealed that gastrointestinal variceal
      bleeding developed after a median interval of 8 months following ascitic
      decompensation in 31 (18.8%) patients, hepatic encephalopathy occurred at 9
      months in 53 (32.1%), spontaneous bacterial peritonitis appeared at 12.7 months
      in 24 (14.5%), hepatorenal syndrome occurred at 8.1 months in five (3%), and
      hepatocellular carcinoma was observed at 21.2 months in 10 (6.1%). The overall
      median survival was 12.4 months. The 1- and 3-year survival rates were 50.7 and
      18.7%. The prognostic factors that independently correlated with survival at the
      time of ascitic decompensation were Child-Pugh classification B/C (P = 0.030),
      serum white blood cell (WBC; P = 0.035), serum creatinine (Cr; P = 0.039), serum
      sodium (Na; P = 0.010), and antiviral therapy (P = 0.040). CONCLUSIONS: The
      prognosis of HBV-related cirrhotic patients with ascitic decompensation is poor.
      Child-Pugh class, serum WBC/Cr/Na, and antiviral therapy primarily influenced
      survival.

PMID- 18717758
TI  - Early upregulation of cyclooxygenase-2 in human papillomavirus type 16 and
      telomerase-induced immortalization of human esophageal epithelial cells.
AB  - BACKGROUND AND AIM: Cyclooxygenase-2 (COX-2) plays an important role in the
      carcinogenesis of esophageal squamous cell carcinoma (ESCC). However, it is not
      clear whether COX-2 is involved in the early or late stage of the development of
      ESCC. The aim of this study was to investigate the role of COX-2 in the
      carcinogenesis of ESCC by an immortalized esophageal epithelial cell line.
      METHODS: Human papillomavirus type 16 (HPV16)-E6/E7 and human telomerase reverse
      transcriptase (hTERT) transfection were used for immortalization of esophageal
      epithelial cells. COX-2-specific RNA interference was used for the inhibition of
      COX-2 expression. RESULTS: An immortalized esophageal epithelial cell line, NE6
      E6E7/hTERT, was established, which had high proliferation activity but failed to
      induce colony formation in soft agar. COX-2 expression was upregulated in the
      early process of immortalization, while COX-2 small interfering RNA (siRNA)
      decreased the Bcl-2 expression, increased the expression of Bax, and induced cell
      cycle arrest at the G0/G1 phase in NE6-E6E7/hTERT cells. Expressions of p53,
      cyclinD1, and the ratio of hyperphosphorylated-RB/hypophosphorylated-RB were
      progressively increased after E6E7 and the subsequent hTERT transfections. These
      changes were accompanied by the alteration of COX-2 expression, but could be
      reversed by COX-2 siRNA (P < 0.05). P16 expression was significantly
      downregulated in NE6-E6E7 or NE6-E6E7/hTERT cells (P < 0.05), and was not
      affected by COX-2 siRNA. CONCLUSIONS: Our results suggest that induction of
      cyclooxygenase-2 is essential in the human papillomavirus type 16 and hTERT
      induced immortalization of human esophageal epithelial cells, and that COX-2
      inhibition may be a potential target to block the carcinogenesis of ESCC at the
      precancerous stage.

PMID- 18717759
TI  - Microarray analysis of mitogenic effects of T3 on the rat liver.
AB  - BACKGROUND AND AIM: A single dose of the thyroid hormone tri-iodothyronine, T3,
      can enhance both size and function of normal rodent liver, which is potentially
      of value in the treatment of liver disease. However the mechanism of this has not
      been fully elucidated, and it cannot be modeled in vitro. We therefore
      investigated the transcriptome response to T3 in rat liver in vivo. METHODS:
      After adult rats were administered 5 microg T3 subcutaneously, a whole rat genome
      microarray comparing global hepatic gene expression against vehicle-only treated
      liver after 3 h was performed. RESULTS: Informative transcripts which had
      identifiable gene ontology biological processes were grouped according to
      function, broadly reflecting general metabolic effects and those linked to cell
      proliferation control. We then compared the transcriptome response after 5-microg
      T3 initiating hepatocyte DNA synthesis (mitogenic) with that after 0.1 microg T3,
      a supraphysiological amount not initiating hepatocyte DNA synthesis. CONCLUSIONS:
      We compared the results with published results of the response to other primary
      mitogens, and identified the Gadd45beta/MyD118 gene as a common early factor
      upregulated during proliferation.

PMID- 18717760
TI  - Increased melibiose/rhamnose ratio in bile of rats with acute cholestasis.
AB  - BACKGROUND AND AIM: Melibiose/rhamnose permeability test is used for noninvasive
      intestinal mucosa barrier testing. However, the possible escape route of the
      absorbed saccharides through either intact or impaired blood-biliary barriers has
      not so far been explored. The objective of the present study was therefore two
      fold: First, to describe in detail the biliary pharmacokinetics of melibiose and
      rhamnose in rats; second, to evaluate the changes of both sugars'
      pharmacokinetics upon impairment of the blood-biliary barrier by acute
      extrahepatic cholestasis in rats. METHODS: Bile duct obstructed (BDO), sham
      operated and intact (unoperated) male Wistar rats were administered, 24 h after
      the appropriate intervention, with a single intravenous dose of melibiose and
      rhamnose, and a 4-h pharmacokinetic study was performed. RESULTS: In intact
      animals, the biliary excretion of melibiose and rhamnose was only 0.06% and 0.4%
      of the administered dose, respectively, while the urinary excretion accounted for
      70.6% and 61.7%, respectively. In BDO animals, the biliary excretion rate of both
      saccharides, especially that of melibiose, was increased with a consequent 4.4
      fold rise of the biliary melibiose/rhamnose ratio, the accepted paracellular
      permeability indicator. Both, the renal clearance of melibiose and the urinary
      melibiose/rhamnose ratio remained uninfluenced by cholestasis. CONCLUSION: The
      present study is the first to describe in detail pharmacokinetic parameters and
      the biliary excretion of melibiose and rhamnose in healthy and cholestatic rats.
      The altered melibiose/rhamnose biliary excretion ratio in BDO rats indicates that
      the test is able to detect the impairment of the blood-biliary barrier in acute
      extrahepatic cholestasis.

PMID- 18717761
TI  - Effects of branched-chain amino acids-enriched nutrient support for patients
      undergoing liver resection for hepatocellular carcinoma.
AB  - BACKGROUND AND AIMS: Most patients with hepatocellular carcinoma (HCC) have
      underlying liver cirrhosis that is frequently associated with a state of protein
      energy malnutrition. The aim of this study was to evaluate the clinical benefit
      of perioperative supplementation of a branched-chain amino acid-enriched nutrient
      mixture for patients undergoing liver resection for HCC. METHODS: A total of 112
      patients with HCC who underwent hepatic resection were enrolled in this study.
      These patients were divided into two groups: 40 patients received perioperative
      supplementation of branched-chain amino acid-enriched nutrient-mixture (AEN
      group) and 72 patients did not (control group). Laboratory data, postoperative
      complications, duration of hospitalization, and survival were assessed for each
      group and compared. RESULTS: The overall incidence of postoperative complications
      was lower in the AEN group (17.5%) than in the control group (44.4%) (P = 0.01).
      Among the postoperative complications, surgical site infection and bile leakage
      was observed in 5% of patients in the AEN group and in 15.3% and 12.5% of
      patients in the control group, respectively. Ascites appeared after the surgery
      in 7.5% of patients in the AEN group and in 16.7% of patients in the control
      group. The duration of hospitalization was significantly shorter in the AEN group
      was than in the control group (P < 0.05). CONCLUSIONS: This study strongly
      suggests that perioperative supplementation of a branched-chain amino acid
      enriched nutrient-mixture is clinically beneficial in reducing the morbidity
      associated with postoperative complications and in shortening the duration of
      hospitalization of patients with chronic liver disease who undergo liver
      resection for HCC.

PMID- 18717762
TI  - Risk factors for the development of diabetes mellitus in chronic hepatitis C
      virus genotype 4 infection.
AB  - BACKGROUND AND AIM: A high occurrence of type 2 diabetes (T2D) in patients with
      chronic hepatitis C virus (HCV) infection has been reported in Kuwait and other
      countries. However, HCV genotype 4 has been underrepresented in all previous
      studies. Our aim was to investigate the viral and host risk factors associated
      with the development of T2D in patients with chronic hepatitis C genotype 4
      infection in the absence of liver fibrosis and steatosis. METHODS: The study
      population consisted of 181 HCV-positive patients and 170 control HCV-negative
      patients with T2D. RESULTS: The prevalence of HCV-patients with T2D was 39.8%.
      There was no significant association of T2D with gender, nationality, obesity,
      HCV viral load, or antiviral therapy. Older age (>or= 50 years) and family
      history of diabetes were the only independent risk factor for T2D in HCV
      patients. However, the median age and the prevalence of obesity in HCV-positive
      patients with T2D were significantly lower than those in diabetic HCV-negative
      patients. By following-up HCV-patients receiving antiviral drugs, a significant
      decrease of fasting plasma glucose and glycosylated hemoglobin levels was
      observed in diabetic patients who achieved a sustained viral response (SVR).
      CONCLUSIONS: The risk factors associated with the development of T2D in the
      general population cannot alone account for the high prevalence of T2D obtained
      in chronic HCV genotype 4 infection. In the absence of liver fibrosis and
      steatosis, the improvement in glycemic control obtained in SVR patients may imply
      direct involvement of HCV in the development of T2D.

PMID- 18717764
TI  - Measurement of problem behaviour during medication evaluations.
AB  - BACKGROUND: The focus of this review is on methods that are currently being used
      to evaluate the behavioural effects of medication for individuals with
      intellectual disabilities. First we describe what has been identified as the
      ideal criteria for conducting clinical trials and how these criteria may be
      adapted to do less controlled evaluations. The central theme is a review of the
      biological measures (e.g. labs, drug levels), behavioural rating scales and
      direct observation measures that are often used to evaluate medication effects.
      Issues related to how the side effects of medication can affect behaviour will
      also be discussed. CONCLUSION: The importance of encouraging communication and
      collaboration across all systems of care and the use of socially valid measures
      are discussed.

PMID- 18717763
TI  - Cholangiocyte bile salt transporters in cholesterol gallstone-susceptible and
      resistant inbred mouse strains.
AB  - BACKGROUND AND AIM: We investigated the dietary and gender influences on the
      expression and functionality of cholangiocyte bile salt transporters and
      development of biliary hyperplasia in cholesterol gallstone-susceptible C57L/J
      and resistant AKR/J mice. METHODS: C57L and AKR mice were fed chow, a lithogenic
      diet, or a cholic acid-containing diet for 14 days. Expression of cholangiocyte
      bile salt transporter proteins ASBT (SLC10A2), ILBP (FABP6), and MRP3 (ABCC3)
      were studied by Western blot analysis. Taurocholate uptake studies were performed
      using microperfusion of isolated bile duct units. The pre- and post-perfusion
      taurocholate concentrations were analyzed by high performance liquid
      chromatography. Biliary proliferation in liver sections was scored. RESULTS: The
      lithogenic diet induced ductular proliferation in C57L mice. On chow, SLC10A2 and
      ABCC3 were overexpressed in male and female C57L compared to AKR mice. A
      lithogenic diet reduced the expressions of FABP6 in both male and female C57L
      mice, SLC10A2 in female C57L mice, and ABCC3 in male C57L mice. These alterations
      in transporter expressions were not associated with changes in taurocholate
      uptake. The lithogenic diet induced biliary hyperplasia and reduced bile salt
      transporter expressions in C57L mice. CONCLUSIONS: Although bile salt uptake was
      not increased in the bile duct unit, we speculate that the biliary hyperplasia on
      the lithogenic diet may lead to an increase in intrahepatic bile salt recycling
      during cholesterol cholelithogenesis.

PMID- 18717766
TI  - Apgar scores reported in personal child health records: validity for
      epidemiological studies?
AB  - AIM: In epidemiological studies on children, information in the neonatal period
      that might affect children's long-term health could be extracted from the
      personal child health record (PCHR), because the booklet exists in most
      countries. We aimed to assess, in individual children, the validity of Apgar
      scores reported in the PCHR using maternity medical records as the gold standard.
      METHODS: In two French hospitals, 435 women who had a child in January 2006 were
      recruited and 90% filled in a postal questionnaire 6 weeks after delivery,
      copying neonatal information (including Apgar scores) from the PCHR. This
      information was compared with data independently recorded at birth by physicians
      in maternity medical records. RESULTS: We found that the proportion of missing
      Apgar scores in the PCHR was higher when scores in the medical records were
      lower. Moreover, Apgar scores reported in the PCHR were overestimated when scores
      in the medical records were low. Using medical records as the gold standard,
      specificity for PCHR-reported 1-min Apgar score was 100% and sensitivity 33%.
      Similar trends were found for the 5-min score. This supports the hypothesis that
      information considered as 'socially sensitive' by physicians may be intentionally
      altered in PCHRs. CONCLUSIONS: Apgar scores reported in PCHRs may not yield
      reliable information for epidemiological studies. When the PCHR is the only
      source of information for the neonatal period in an epidemiological study, it
      would be preferable to use a composite neonatal indicator rather than the Apgar
      score.

PMID- 18717767
TI  - Attitudes to HIV testing among carers of children admitted to Port Moresby
      General Hospital, Papua New Guinea.
AB  - AIM: To assess the acceptability of voluntary counselling and testing among the
      carers of children admitted to hospital in Papua New Guinea. METHODS: Forty
      semistructured interviews were carried out between February and April 2007.
      RESULTS: All the carers interviewed were women, mostly from Port Moresby.
      Virtually all of them attended primary school. About half of them attended
      secondary school but none completed it. Half of them knew an adult or child with
      HIV. Three quarters of the women interviewed would consent to having a child in
      their care tested for HIV, and over half of those who had never been tested would
      agree to be tested themselves. Correct answers to more than half the HIV
      knowledge questions posed were significantly related to agreement to an HIV test.
      CONCLUSIONS: This study supports the need for further evaluation of knowledge
      about HIV/AIDS and opportunities for health promotion in this group of women,
      particularly in view of the implication for voluntary counselling and testing and
      prevention of mother-to-child HIV transmission programmes in Papua New Guinea.

PMID- 18717768
TI  - An undergraduate paediatric curriculum based on clinical presentations and 'key
      features'.
AB  - AIM: We wanted to develop and define an undergraduate paediatric curriculum in a
      way that would facilitate the development of clinical reasoning. METHOD: We sent
      a series of four questionnaires to paediatricians in New Zealand to explore their
      perceptions of common presenting complaints for an undergraduate paediatrics
      curriculum. The final group of paediatricians consulted had no further
      suggestions to add to the twenty five presentations that had already been listed.
      Further consultation lead to the determination of the knowledge and skills
      students' require in order to assess and manage these presentations. RESULT: We
      have defined with wide consultation, a framework for an undergraduate paediatric
      curriculum suitable for New Zealand. CONCLUSIONS: When consulting with a range of
      experts it can be difficult to reach agreement. By describing the curriculum as a
      series of presenting complaints and using the concept of 'key features' we were
      able to reach agreement on the content and details of an undergraduate curriculum
      for paediatrics.

PMID- 18717769
TI  - Feeding problems in preterm infants of preeclamptic mothers.
AB  - AIM: Maternal disease can cause prematurity and neonatal complications, notably
      feeding problems. To determine the relationship between maternal disease and the
      nature and severity of neonatal feeding problems, we compared feeding profiles,
      time to demand feeding and length of hospital stay between preterm infants of
      preeclamptic mothers, mothers with amniotic infection and mothers with other
      disease causing prematurity. METHODS: The retrospective study used labour ward
      data collected from 2002 to 2005 in a tertiary university centre to analyse three
      groups of singletons born at <32 completed gestational weeks to mothers with
      preeclampsia (n = 61), amniotic infection (n = 55) and non-preeclamptic non
      amniotic infection controls (n = 55). The groups were similar in gestational age,
      birthweight and sex ratio; all infants received enteral feeding according to
      departmental guidelines. Feeding profiles and enteral/oral nutrition were
      compared. RESULTS: Feeding problems occurred in 46% of the preeclamptic group,
      11% of the amniotic infection group and 13% of controls. Full oral demand feeding
      was established at 36 0/7 weeks postmenstrual age, 35 3/7 weeks (P = 0.03) and 35
      2/7 weeks (P < 0.0001), respectively. Feeding problems were the main cause of
      delay (7-10 days) in hospital discharge in the preeclamptic group (P = 0.0002).
      CONCLUSIONS: Feeding problems are greater, and hospital stay longer, in preterm
      infants of preeclamptic mothers than in other preterm infants.

PMID- 18717770
TI  - Epidemiology and outcome of acute kidney injury in New Zealand children.
AB  - OBJECTIVES: To determine the aetiology, incidence and short-term outcomes of New
      Zealand children with acute kidney injury (AKI) requiring renal replacement
      therapy (RRT) over a 6-year period. METHODS: A retrospective chart review of all
      children requiring RRT for AKI from January 2001 to December 2006 at Starship
      Children's Hospital, Auckland, New Zealand was conducted. The primary outcome was
      survival to discharge. RESULTS: A total of 226 children required RRT for AKI over
      the 6-year study period. The annual incidence was 4.0 per 100,000 total
      population under 15 years of age. The commonest causes of AKI were post cardiac
      surgery (58%), haemolytic uraemic syndrome (17%), sepsis (13%) and
      glomerulonephritis (4%). The survival rate to hospital discharge was 89%. A total
      of 40% of all surviving children had one or more abnormalities at the time of
      discharge suggestive of ongoing renal dysfunction (hypertension, continuing need
      for antihypertensive medication, reduced estimated glomerular filtration rate or
      abnormal urinalysis). More Maori and Pacific Island children were treated for AKI
      than would be expected from population data (P < 0.0001). Sepsis and
      glomerulonephritis were seen more commonly as causes of AKI in Maori and Pacific
      Island children compared with New Zealand European children. CONCLUSION: In our
      study, 40% of surviving children had evidence of short-term renal dysfunction at
      discharge following AKI. This suggests that all children should undergo a period
      of follow-up after any episode of AKI to look for resolution or further
      development of signs of renal injury.

PMID- 18717771
TI  - Use of health care by young Asian New Zealanders: findings from a national youth
      health survey.
AB  - AIM: To examine the use of health services and perceived barriers to accessing
      health care among young Asian New Zealanders. METHODS: Secondary analysis of data
      from Youth2000, a cross-sectional survey of secondary school students in New
      Zealand (NZ) conducted in 2001. Of the 9567 survey participants (aged 12-18
      years), this study was restricted to students who identified with an 'Asian'
      ethnic category (n = 922). RESULTS: Chinese and Indian students (the largest
      Asian ethnic groups in NZ) reported levels of overall health comparable to NZ
      European (NZE) students. However, relative to NZE students, Chinese students were
      more likely to report (i) not having a usual location for health care (adjusted
      OR 3.28; 95% CI: 2.51-4.43); and (ii) having problems getting health care when
      they needed it (adjusted OR 1.61; 95% CI: 1.32-1.96). Asian students who had been
      in NZ for 5 years or less (compared with NZ-born students), as well as those who
      did not speak English at home (compared with those who did) were less likely to
      report having a usual source of health care, even after adjusting for their
      overall health (adjusted OR 2.13, 95% CI: 1.27-3.56; and adjusted OR 1.69, 95%
      CI: 1.11-2.56, respectively). CONCLUSION: Young Asian New Zealanders are less
      likely to access health care than their NZE counterparts. The perceived barriers
      require explicit attention within the broader platforms of health-care quality,
      and professional and cultural competence of health-care services.

PMID- 18717772
TI  - Implementing a strategic plan for child health: a Sydney case study.
AB  - AIM: The aim of this paper is to describe the implementation of a strategic plan,
      Health Gain for Children and Youth of Central Sydney, over a 10-year period to
      December 2005. METHODS: Descriptive information was obtained from the records and
      minutes of all relevant committees, interviews with key workers who were involved
      with the committees, managers and senior health professionals, and from the
      involvement of the authors throughout the process of the implementation. RESULTS:
      An implementation steering committee was established to oversee the
      implementation of the plan. Rather than adopting a uniform approach to assigning
      responsibility for the implementation of each strategy in the plan or developing
      specific costs and time frames for each strategy, a more pragmatic, flexible and
      opportunistic approach was taken. Most of the plan's strategies were implemented
      over a 7-year time frame using a combination of service reorientation and
      implementation of new programmes, some of which were funded from sources not
      anticipated during the development of the plan. Implementation required a
      dedicated driver, commitment at senior level and participation by many staff at
      many levels. Outcomes, monitored through data collected at 5-year intervals,
      revealed positive trends in a number of child and youth health indicators.
      CONCLUSIONS: The successful implementation of the strategic plan required
      pragmatism, flexibility, opportunism and the commitment and involvement of staff
      at all organisational levels. It is envisaged that this approach provides a firm
      base for future evidence-based developments to benefit the health and well-being
      of children, youth and their families and reduce health inequities.

PMID- 18717773
TI  - Anthropometry and renal size of children suffering under sustained conflict in
      Sri Lanka.
AB  - AIM: To measure anthropometry, blood pressure and renal lengths of children in a
      war torn region of Sri Lanka and compare results with local and international
      standards. METHODS: Measurements of 147 Tamil children in Kilinochchi, north-east
      Sri Lanka, were compared with the World Health Organization standards using
      Anthro 2005 software in a period of relative peace in December 2005. Renal
      lengths were measured by ultrasound and compared with Australian and Indian data.
      RESULTS: 1 2-5 years of age. The weight-to-height ratio for combined sexes
      revealed 13.9% were <-3 standard deviations (SD) and 33.3% <-2 SD. The height-to
      age ratio revealed 5.6% <-3 SD and 22.2% <-2 SD. The weight-to-age ratio revealed
      13.9% <-3 SD and 38.9% <-2 SD. The body mass index of 13.9% of children was <-3
      SD, of 25% it was <-2 SD. Stunting and wasting is prevalent, and worse than in
      other areas of Sri Lanka, except in tea estates. 2 5-12 years. The height-to-age
      ratio for combined sexes revealed 15.7% were <-3 SD and 38.5% <-2 SD. The weight
      to-age ratio revealed 6.1% were <-3 SD and 47.3% <-2 SD. The body mass index of
      64.0% of children was <5th percentile. More children are stunted and wasted in
      this older group. Girls are more affected than boys. 3 Renal lengths fell
      progressively below -2 SD for both age and height when compared with Australian
      and Indian children. CONCLUSION: Tamil children in Kilinochchi are more stunted
      and wasted than others in Sri Lanka, except those in the tea estates. Progressive
      renal stunting because of under-nutrition may be a mechanism for later disease.
      The loss of potential for human development can only be addressed by long-term
      improvement in access to nutrition.

PMID- 18717774
TI  - Diagnosis and management of childhood obesity: a survey of general practitioners
      in South West Sydney.
AB  - AIM: To describe general practitioners' (GPs) diagnosis and management of
      overweight and obesity in children, their attitudes regarding obesity and their
      awareness of National Health and Medical Research Council (NHMRC) clinical
      practice guidelines. METHOD: A cross-sectional written survey of members of the
      Liverpool Division of General Practice (located in South West Sydney, Australia).
      RESULTS: Of 137 questionnaires sent, 85 (62%) were returned. Although the
      majority prescribed the correct interventions, there was variability in
      complications screening, ranging from 75% screening for psychosocial problems to
      30% for fatty liver. Less than a third (28%) of GPs used NHMRC guidelines in
      their practice and only 9% used body mass index charts to correctly diagnose
      childhood obesity. GPs felt that childhood obesity was a significant issue and
      identified parental denial and lack of community support as barriers to
      treatment. CONCLUSION: Although NHMRC guideline adherence was far from universal,
      the GPs in our survey are motivated and aware of the importance of managing
      childhood obesity. If the primary care approach is to work, then GPs need support
      and education in an environment where there is greater community awareness of the
      impact of childhood obesity.

PMID- 18717776
TI  - Predicting intentions to donate blood among nondonors in Australia: an extended
      theory of planned behavior.
AB  - BACKGROUND: With an increasing demand for blood and blood products in Australia,
      there is a continual need to recruit blood donors. As such, it is important to
      investigate the factors that impact on nondonors' decision-making processes with
      regard to donating blood for the first time. Previous research has established
      the efficacy of the theory of planned behavior (TPB) in predicting blood donor
      intentions. The current research aimed to test a TPB model augmented with
      constructs implicated in previous blood donor research; specifically descriptive
      norm, moral norm, anticipated regret, and donation anxiety. STUDY DESIGN AND
      METHODS: Participants completed measures assessing the standard TPB variables of
      attitude, subjective norm, and perceived behavioral control (PBC) as well as
      descriptive norm, moral norm, donation anxiety, and anticipated regret. Path
      analysis examined the utility of the augmented TPB model to predict 195 non-blood
      donors' intentions to donate blood. RESULTS: A final revised model provided a
      very good fit to the data and included attitude, PBC, moral norm, descriptive
      norm, anticipated regret, and donation anxiety as direct predictors of intention,
      with these factors accounting for 70 percent of the variance in intentions to
      donate blood. CONCLUSION: A revised TPB model provided a more efficacious
      predictor of nondonors' intentions to donate than the standard TPB model and
      highlights the role that norm-based factors and affective-laden constructs play
      in predicting non-blood donors' intentions to donate.

PMID- 18717775
TI  - Metabolism of melatonin by cytochrome P450s in rat liver mitochondria and
      microsomes.
AB  - In the present study we provide direct evidence for the involvement of rat
      microsomal cytochrome P450s in melatonin O-demethylation and hydroxylation at two
      different positions: 2 and 6, as well as generation of N(1)-acetyl-N(2)-formyl-5
      methoxy-kynuramine (AFMK) and two unknown products. Moreover, we found that
      mitochondrial cytochrome P450s also converts melatonin into AFMK, N
      acetylserotonin, 2-hydroxymelatonin, 6-hydroxymelatonin and the same two unknown
      products. Eadie-Hofstee plots for 6-hydroxylation and O-demethylation reactions
      were curvilinear for all tested fractions, suggestive of involvement of at least
      two components, one with a high affinity and low capacity, and another with a low
      affinity and high capacity. Mitochondrial cytochrome P450s exhibited higher
      affinity (suggesting lower K(m) value) and higher V(max) for melatonin 6
      hydroxylation and O-demethylation for both high-affinity and low-affinity
      components as compared with microsomal enzymes. The intrinsic clearance for
      melatonin hydroxylation by high- and low-affinity components displayed the
      highest values in all tested fractions, indicating that both mitochondrial and
      microsomal cytochrome P450s metabolize melatonin principally by 6-hydroxylation,
      with O-demethylation representing a minor metabolic pathway.

PMID- 18717777
TI  - Donor deferral and resulting donor loss at the American Red Cross Blood Services,
      2001 through 2006.
AB  - BACKGROUND: A large number of blood donors are deferred each year and many of the
      temporarily deferred donors do not return to donate blood. This study analyzed
      actual deferral and return donation data from the American Red Cross to further
      assess the impact of donor deferral on donor availability. STUDY DESIGN AND
      METHODS: Voluntary blood donors who presented between 2001 and 2006 were included
      in this study. Deferred donors were classified into three groups according to
      their history of presentation during the prior 2 years: Group 1 with no prior
      donation or deferral, Group 2 with prior donation but no deferral, and Group 3
      with prior deferral. Temporarily deferred donors in Groups 1 and 2 who did not
      return during the next 3 years were considered lost donors. All indefinitely
      deferred donors were lost donors. RESULTS: A mean of 12.8 percent of a total of
      47,814,370 donor presentations between 2001 and 2006 resulted in a deferral.
      While majority of the deferrals were related to donor safety reasons, deferrals
      for recipient safety reasons accounted for 22.6 percent of deferrals or 2.9
      percent of total presentations. Temporary and indefinite deferrals for recipient
      safety-related reasons collectively caused an estimated loss of 647,828 donors
      during the 6 years. An additional 1,042,743 donors were lost due to deferrals for
      donor safety-related reasons during the same period. CONCLUSIONS: The results on
      donor loss after deferral call attention to the impact of donor deferrals on
      donor availability and the need to monitor and assess the necessity and
      effectiveness of such deferrals.

PMID- 18717778
TI  - Testing only donors with a prior history of pregnancy or transfusion is a logical
      and cost-effective transfusion-related acute lung injury prevention strategy.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of
      transfusion-related fatality reported to the Food and Drug Administration. Donor
      screening may reduce TRALI risk. This study sought to compare the efficacy and
      safety of different TRALI risk-reduction strategies at a hospital-based donor
      center. STUDY DESIGN AND METHODS: Samples from 1053 donors who answered questions
      regarding pregnancy and transfusion history were tested for HLA Class I and II
      antibodies using a flow cytometry-based screening assay. Donor history was
      compared with the presence of HLA alloantibodies. These data were used to model
      several TRALI risk-reduction strategies. The medical records of patients
      transfused fresh-frozen plasma (FFP) from highly alloimmunized donors were
      retrospectively reviewed for TRALI. RESULTS: HLA alloimmunization was observed
      among 25.4 percent (256/1009) of all female donors and among 12.0 percent (3/25)
      of those male donors who gave a history of prior transfusion. Prior pregnancy,
      reported by 52.6 percent (531/1009) of females, correlated significantly with HLA
      alloimmunization (p < 0.0001). The rate of HLA alloimmunization increased with
      parity. A positive pregnancy history was a sensitive (87.9%) screen for HLA
      alloimmunization with a negative predictive value of 93.5 percent (95% confidence
      interval, 91.3%-95.7%). Although 5.9 percent (27/459) of nulliparous,
      untransfused females demonstrated a positive screening test, only 1 percent
      (7/459) had a confirmed HLA alloantibody. Transfusion of FFP from donors found
      retrospectively to be highly alloimmunized led to reactions suggestive of TRALI
      in 2 of 26 recipients. CONCLUSIONS: Donor history is a reliable predictor of HLA
      alloimmunization. Testing only donors with a prior history of pregnancy or
      transfusion is a logical and cost-effective TRALI prevention strategy.

PMID- 18717779
TI  - The gingipains from Porphyromonas gingivalis do not directly induce osteoclast
      differentiation in primary mouse bone marrow cultures.
AB  - BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis is a major aetiological agent
      in the development of periodontitis, the major clinical hallmark of which is bone
      resorption. The cysteine proteases (gingipains) produced by P. gingivalis have a
      critical role in the pathogenesis of the disease, and previous studies on whole
      bacteria have implicated these enzymes in osteoclastogenesis, a process which
      serves to upregulate bone resorption. The effects of the gingipains from P.
      gingivalis on osteoclast differentiation were investigated here to determine
      whether the enzymes directly contribute to osteoclastogenesis and thus to bone
      resorption. MATERIAL AND METHODS: The effects of the gingipains on osteoclast
      differentiation were investigated in primary mouse bone marrow cultures. The
      cultures harvested from C57BL6/J mice were incubated in the presence of
      parathyroid hormone, a known osteoclastogenic factor, or active/inactivated forms
      of three gingipains. Osteoclast differentiation was quantified by counting the
      number of multinucleated cells positive for tartrate-resistant acid phosphatase,
      an enzyme marker for these cells. RESULTS: After 10 days of culture, the
      gingipains, either active or inactive, failed to stimulate osteoclast
      differentiation in comparison to the parathyroid hormone. CONCLUSION: The data
      presented here demonstrate that the gingipains do not induce osteoclast
      differentiation in this system, indicating that the bacterium uses other
      mechanisms to induce bone loss.

PMID- 18717780
TI  - Effects of cytomegalovirus infection on the mRNA expression of collagens and
      matrix metalloproteinases in gingival fibroblasts.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this in vitro investigation was to study
      the effects of human cytomegalovirus infection on the mRNA expression for
      collagens I and III and for matrix metalloproteinases 1 and 2 in gingival
      fibroblasts. MATERIAL AND METHODS: Gingival fibroblasts were experimentally
      infected with the Towne strain of human cytomegalovirus and the kinetics of
      expression of mRNA for collagens I and III and for matrix metalloproteinases 1
      and 2 was studied at different time-points. Total RNA was isolated at the
      indicated time, and the reverse transcription-polymerase chain reaction was used
      to analyze the level of mRNA expression. In addition, gingival specimens were
      obtained from 14 periodontitis and from three non-periodontitis subjects and mRNA
      analysis for collagens and metalloproteinases was carried out. Nested polymerase
      chain reaction was used to determine the presence or absence of human
      cytomegalovirus in subgingival samples from each subject. RESULTS: The infection
      of gingival fibroblasts with human cytomegalovirus during a 0-72-h period
      resulted in progressive reduction in the expression of mRNA for collagens I and
      III (p < 0.05). A higher concentration of human cytomegalovirus resulted in
      varying degrees of mRNA reduction, suggesting a virally mediated effect. Biopsies
      from human cytomegalovirus-positive individuals with periodontitis had a higher
      expression of mRNA for collagens I and III than biopsies from human
      cytomegalovirus-negative individuals. An up-regulation in the mRNA expression of
      matrix metalloproteinases 1 and 2 over time was observed (p < 0.05). Analysis of
      mRNA expression in gingival biopsies demonstrated higher expression of matrix
      metalloproteinase-1 in human cytomegalovirus-positive periodontitis specimens
      compared with human cytomegalovirus-negative periodontitis specimens. CONCLUSION:
      Altered expression of mRNA for collagens and metalloproteinases in human
      cytomegalovirus-infected gingival fibroblasts should be considered as possible
      modifying mechanisms in periodontitis-infected sites.

PMID- 18717787
TI  - Structural basis of specific TraD-TraM recognition during F plasmid-mediated
      bacterial conjugation.
AB  - F plasmid-mediated bacterial conjugation requires interactions between a
      relaxosome component, TraM, and the coupling protein TraD, a hexameric ring
      ATPase that forms the cytoplasmic face of the conjugative pore. Here we present
      the crystal structure of the C-terminal tail of TraD bound to the TraM
      tetramerization domain, the first structural evidence of relaxosome-coupling
      protein interactions. The structure reveals the TraD C-terminal peptide bound to
      each of four symmetry-related grooves on the surface of the TraM tetramer.
      Extensive protein-protein interactions were observed between the two proteins.
      Mutational analysis indicates that these interactions are specific and required
      for efficient F conjugation in vivo. Our results suggest that specific
      interactions between the C-terminal tail of TraD and the TraM tetramerization
      domain might lead to more generalized interactions that stabilize the relaxosome
      coupling protein complex in preparation for conjugative DNA transfer.

PMID- 18717789
TI  - A technique to improve the success of light guided retrograde intubation.

PMID- 18717788
TI  - Molecular basis of halorespiration control by CprK, a CRP-FNR type
      transcriptional regulator.
AB  - Certain bacteria are able to conserve energy via the reductive dehalogenation of
      halo-organic compounds in a respiration-type metabolism. The transcriptional
      regulator CprK from Desulfitobacterium spp. induces expression of halorespiratory
      genes upon binding of o-chlorophenol ligands and is reversibly inactivated by
      oxygen through disulphide bond formation. We report crystal structures of D.
      hafniense CprK in the ligand-free (both oxidation states), ligand-bound (reduced)
      and DNA-bound states, making it the first member of the widespread CRP-FNR
      superfamily for which a complete structural description of both redox-dependent
      and allosteric molecular rearrangements is available. In conjunction with kinetic
      and thermodynamic ligand binding studies, we provide a model for the allosteric
      mechanisms underpinning transcriptional control. Amino acids that play a key role
      in this mechanism are not conserved in functionally distinct CRP-FNR members.
      This suggests that, despite significant structural homology, distinct allosteric
      mechanisms are used, enabling this protein family to control a very wide range of
      processes.

PMID- 18717790
TI  - Sheath of guidewire of ureteric stent as an aid to extubation in difficult
      pediatric airway.

PMID- 18717791
TI  - Safe and successful intubation using a Storz video laryngoscope in management of
      pediatric difficult airways.

PMID- 18717792
TI  - Anesthetic management of subglottic stenosis complicating tracheo-esophageal
      fistula in a newborn.

PMID- 18717793
TI  - Do infants need higher intrathecal fentanyl doses than older children?

PMID- 18717794
TI  - Capnography guided retrograde intubation with the aid of sheath of fogarty
      embolectomy catheter.

PMID- 18717795
TI  - Difficult proseal laryngeal mask airway placement in a child: made easy by bougie
      guided technique. Comment.

PMID- 18717796
TI  - An innovative nerve stimulating needle.

PMID- 18717797
TI  - Sedation and anesthesia for fiberoptic intubation in management of pediatric
      difficult airways.

PMID- 18717798
TI  - Anesthetic management of esophageal atresia and tracheoesophageal fistula repair
      in a newborn with tricuspid atresia.

PMID- 18717799
TI  - Visual swoosh test.

PMID- 18717800
TI  - An oculomotor palsy developing immediately after a spinal tap in a 6-year-old
      child.

PMID- 18717801
TI  - Ultrasound needle guidance in neonatal and infant caudal anesthesia.

PMID- 18717802
TI  - Effects of dexmedetomidine on intraoperative motor and somatosensory evoked
      potential monitoring during spinal surgery in adolescents.
AB  - BACKGROUND: Dexmedetomidine may be a useful agent as an adjunct to an opioid
      propofol total intravenous anesthesia (TIVA) technique during posterior spinal
      fusion (PSF) surgery. There are limited data regarding its effects on
      somatosensory (SSEPs) and motor evoked potentials (MEPs). METHODS: The data
      presented represent a retrospective review of prospectively collected quality
      assurance data. When the decision was made to incorporate dexmedetomidine into
      the anesthetic regimen for intraoperative care of patients undergoing PSF, a
      prospective evaluation of its effects on SSEPs and MEPs was undertaken. SSEPs and
      MEPs were measured before and after the administration of dexmedetomidine in a
      cohort of pediatric patients undergoing PSF. Dexmedetomidine (1 microg x kg(-1)
      over 20 min followed by an infusion of 0.5 microg x kg(-1) x h(-1)) was
      administered at the completion of the surgical procedure, but prior to wound
      closure as an adjunct to TIVA which included propofol and remifentanil, adjusted
      to maintain a constant depth of anesthesia as measured by a BIS of 45-60.
      RESULTS: The cohort for the study included nine patients, ranging in age from 12
      to 17 years, anesthetized with remifentanil and propofol. In the first patient,
      dexmedetomidine was administered in conjunction with propofol at 110 microg x kg(
      1) x min(-1) which resulted in a decrease in the bispectral index from 58 to 31.
      Although no significant effect was noted on the SSEPs (amplitude or latency) or
      the MEP duration, there was a decrease in the MEP amplitude. The protocol was
      modified so that the propofol infusion was incrementally decreased during the
      dexmedetomidine infusion to achieve the same depth of anesthesia. In the
      remaining eight patients, the bispectral index was 52 +/- 6 at the start of the
      dexmedetomidine loading dose and 49 +/- 4 at its completion (P = NS). There was
      no statistically significant difference in the MEPs and SSEPs obtained before and
      at completion of the dexmedetomidine loading dose. CONCLUSION: Using the above
      mentioned protocol, dexmedetomidine can be used as a component of TIVA during PSF
      without affecting neurophysiological monitoring.

PMID- 18717803
TI  - Modified Trachlight for management of difficult pediatric airway.

PMID- 18717804
TI  - An unusual cause for oropharyngeal leak during use of 2.5 size ProSeal LMA.

PMID- 18717805
TI  - Laryngeal mask airway and difficult airway management in adolescent: a case
      report.

PMID- 18717806
TI  - Cardiac output measurement in pediatric anesthesia.
AB  - Maintenance of cardiovascular stability is crucial to safe anesthetic practice,
      but measurement of cardiac output has been technically challenging, particularly
      in pediatric patients. Cardiovascular monitoring has therefore generally relied
      upon pressure-based measurements, as opposed to flow-based measurements. The
      measurement of cardiac output under anesthesia and in critical care has recently
      become easier as a result of new techniques of measurement. This article reviews
      the basic concepts of and rationale for cardiac output monitoring, and then
      describes the techniques available for monitoring in clinical practice.

PMID- 18717807
TI  - Arterial to endtidal carbon dioxide gradient during pediatric laparoscopic
      fundoplication.
AB  - BACKGROUND: Discrepancies between arterial carbon dioxide (P(a)CO(2)) and
      endtidal carbon dioxide (ETCO(2)) measures have been demonstrated in ventilated
      children with cyanotic congenital heart disease, infants with respiratory failure
      and during visceral and urological laparoscopic surgery. OBJECTIVES: Our
      objective was to assess the extent of the P(a)CO(2) to ETCO(2) gradient in
      children during laparoscopic fundoplication. METHODS: We prospectively collected
      data on patient characteristics, surgical conditions, pH, ETCO(2)and P(a)CO(2)
      during laparoscopic fundoplication using carbon dioxide insufflation in children
      age <29 months. RESULTS: Data were collected on nine cases, four cases aged <1
      year. A P(a)-ETCO(2) gradient was present during insufflation. The gradient was
      larger in children age less than 1 year but statistically significantly different
      from a value of zero, only at t = 30 min (mean = 8 mmHg, sem = 0.81, P = 0.004)
      and t = 60 min (mean = 5 mmHg, sem = 1, P = 0.014). Minute ventilation was
      increased from 20% to 100% to control ETCO(2). CONCLUSIONS: ETCO(2) may not
      accurately represent arterial values during laparoscopic fundoplication,
      especially in the infant when carbon dioxide insufflation is used. Consideration
      should be given to placing an arterial line for blood gas measurement in some
      patients.

PMID- 18717808
TI  - Improving electrical safety for patients with Epidermolysis bullosa.

PMID- 18717809
TI  - Anesthesia for laser treatment for retinopathy of prematurity--all clear now?

PMID- 18717810
TI  - Treatment of neuropathic pain due to sciatic nerve injury following intramuscular
      injection with gabapentin in a child.

PMID- 18717811
TI  - Survival-promoting activity of pituitary adenylate cyclase-activating polypeptide
      in the presence of phosphodiesterase inhibitors on rat motoneurons in culture:
      cAMP-protein kinase A-mediated survival.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to be
      neurotrophic or neuroprotective in various neurons in culture. It is expressed in
      spinal motoneurons in vivo and its expression is increased markedly after
      axotomy, suggesting a neuroprotective role via an autocrine mechanism. However,
      neurotrophic activity of PACAP has not been reported for motoneurons. In the
      present study, we investigated the effects of PACAP on rat motoneurons in
      culture. In the presence of a phosphodiesterase inhibitor, PACAP showed
      significant neurotrophic activity at concentrations as low as 0.01 nM.
      Previously, we found that glutamate was excitotoxic to motoneurons even in the
      presence of brain-derived neurotrophic factor, which is neurotrophic for
      motoneurons. PACAP with a phosphodiesterase inhibitor protected motoneurons
      against this excitotoxicity. The activity of PACAP was inhibited by the protein
      kinase A inhibitor N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide
      dihydrochloride, as was the case with the activity of forskolin, suggesting
      downstream involvement of a cAMP-protein kinase A signaling pathway. The present
      results may suggest a physiological role of PACAP in vivo, and implicate the
      PACAP-cAMP signaling pathway for the possible therapeutic target of amyotrophic
      lateral sclerosis as glutamate excitotoxicity was suggested in sporadic
      amyotrophic lateral sclerosis.

PMID- 18717812
TI  - The co-presence of Na+/Ca2+-K+ exchanger and Na+/Ca2+ exchanger in bovine adrenal
      chromaffin cells.
AB  - We have previously shown that there is high Na(+)/Ca(2+) exchange (NCX) activity
      in bovine adrenal chromaffin cells. In this study, by monitoring the [Ca(2+)](i)
      change in single cells and in a population of chromaffin cells, when the reverse
      mode of exchanger activity has been initiated, we have shown that the NCX
      activity is enhanced by K(+). The K(+)-enhanced activity accounted for a
      significant proportion of the Na(+)-dependent Ca(2+) uptake activity in the
      chromaffin cells. The results support the hypothesis that both NCX and
      Na(+)/Ca(2+)-K(+) exchanger (NCKX) are co-present in chromaffin cells. The
      expression of NCKX in chromaffin cells was further confirmed using PCR and
      northern blotting. In addition to the plasma membrane, the exchanger activity,
      measured by Na(+)-dependent (45)Ca(2+) uptake, was also present in membrane
      isolated from the chromaffin granules enriched fraction and the mitochondria
      enriched fraction. The results support that both NCX and NCKX are present in
      bovine chromaffin cells and that the regulation of [Ca(2+)](i) is probably more
      efficient with the participation of NCKX.

PMID- 18717813
TI  - Differential migration, LPS-induced cytokine, chemokine, and NO expression in
      immortalized BV-2 and HAPI cell lines and primary microglial cultures.
AB  - Microglial cells are hematopoietically derived monocytes of the CNS and serve
      important neuromodulatory, neurotrophic, and neuroimmune roles. Following insult
      to the CNS, microglia develop a reactive phenotype, migrate to the site of
      injury, proliferate, and release a range of proinflammatory, anti-inflammatory,
      and neurotrophic factors. Isolation of primary microglial cell cultures has been
      an integral step in elucidating the many roles of these cells. In addition to
      primary microglial cells, several immortalized cell lines have been created to
      model primary microglia in vitro, including murine-derived BV-2 cells and rat
      derived highly aggressive proliferating immortalized (HAPI) cells. Here, we
      compare rat primary microglial, BV-2, and HAPI cells in experiments assessing
      migration, expression of activation markers, and production and release of nitric
      oxide, cytokines, and chemokines. BV-2 and HAPI cells responded similarly to
      primary microglia in experiments assessing migration, ionized calcium binding
      adaptor molecule 1 expression, and nitric oxide release. However, BV-2 and HAPI
      cells did not model primary microglia in experiments assessing tumor necrosis
      factor-alpha, interleukin-1beta, interleukin-6, and monocyte chemoattractant
      protein-1 expression and release and phospho-extracellular signal-regulated
      kinase 44/42 expression following lipopolysaccharide treatment. These results
      indicate that BV-2 and HAPI cell cultures only partially model primary microglia
      and that their use should therefore be carefully considered.

PMID- 18717814
TI  - Cocaine regulates protein kinase B and glycogen synthase kinase-3 activity in
      selective regions of rat brain.
AB  - Protein kinase B (also known as Akt) signaling regulates dopamine-mediated
      locomotor behaviors. Here the ability of cocaine to regulate Akt and glycogen
      synthase kinase 3 (GSK3) was studied. Rats were injected with cocaine or saline
      in a binge-pattern, which consisted of three daily injections of 15 mg/kg cocaine
      or 1 mL/kg saline spaced 1 h apart for 1, 3, or 14 days. Amygdala, nucleus
      accumbens, caudate putamen, and hippocampus tissues were dissected 30 min
      following the last injection and analyzed for phosphorylated and total Akt and
      GSK3(alpha and beta) protein levels using western blot analysis. Phosphorylation
      of Akt on the threonine-308 (Thr308) residue was significantly reduced in the
      nucleus accumbens and increased in the amygdala after 1 day of cocaine treatment;
      however, these effects were not accompanied by a significant decrease in GSK3
      phosphorylation. Phosphorylation of Akt and GSK3 was significantly reduced after
      14 days of cocaine administration, an effect that was only observed in the
      amygdala. Cocaine did not alter Akt or GSK3 phosphorylation in the caudate
      putamen or hippocampus. The findings in nucleus accumbens may reflect
      dopaminergic motor-stimulant activity caused by acute cocaine, whereas the
      effects in amygdala may be associated with changes in emotional state that occur
      after acute and chronic cocaine exposure.

PMID- 18717815
TI  - IRS-2 branch of IGF-1 receptor signaling is essential for appropriate timing of
      myelination.
AB  - Insulin-like growth factor (IGF)-1 increases proliferation, inhibits apoptosis
      and promotes differentiation of oligodendrocytes and their precursor cells,
      indicating an important function for IGF-1 receptor (IGF-1R) signaling in myelin
      development. The insulin receptor substrates (IRS), IRS-1 and -2 serve as
      intracellular IGF-1R adaptor proteins and are expressed in neurons,
      oligodendrocytes and their precursors. To address the role of IRS-2 in
      myelination, we analyzed myelination in IRS-2 deficient (IRS-2(-/-)) mice and age
      matched controls during postnatal development. Interestingly, expression of the
      most abundant myelin proteins, myelin basic protein and proteolipid protein was
      reduced in IRS-2(-/-) brains at postnatal day 10 (P10) as compared to controls.
      myelin basic protein immunostaining in P10-IRS-2(-/-) mice revealed a reduced
      immunostaining, but an unchanged regional distribution pattern. In cerebral
      myelin isolates at P10 unaltered relative expression of different myelin proteins
      was found, indicating quantitatively reduced but not qualitatively altered
      myelination. Interestingly, up-regulation of IRS-1 expression and increased IGF
      1R signaling were observed in IRS-2(-/-) mice at P10-14, indicating a
      compensatory mechanism to overcome IRS-2 deficiency. Adult IRS-2(-/-) mice showed
      unaltered myelination and motor function. Furthermore, in neuronal/brain-specific
      insulin receptor knockout mice myelination was unchanged. Thus, our experiments
      reveal that IGF-1R/IRS-2 mediated signals are critical for appropriate timing of
      myelination in vivo.

PMID- 18717817
TI  - Activation of nociceptin/orphanin FQ-NOP receptor system inhibits tyrosine
      hydroxylase phosphorylation, dopamine synthesis, and dopamine D(1) receptor
      signaling in rat nucleus accumbens and dorsal striatum.
AB  - Nociceptin/orphanin FQ (N/OFQ) has been reported to inhibit dopamine (DA) release
      in basal ganglia mainly by acting on NOP receptors in substantia nigra and
      ventral tegmental area. We investigated whether N/OFQ could affect DA
      transmission by acting at either DA nerve endings or DA-targeted post-synaptic
      neurons. In synaptosomes of rat nucleus accumbens and striatum N/OFQ inhibited DA
      synthesis and tyrosine hydroxylase (TH) phosphorylation at Ser40 via NOP
      receptors coupled to inhibition of the cAMP/protein kinase A pathway.
      Immunofluorescence studies showed that N/OFQ preferentially inhibited phospho
      Ser40-TH in nucleus accumbens shell and that in this subregion NOP receptors
      partly colocalized with either TH or DA D(1) receptor positive structures. In
      accumbens and striatum N/OFQ inhibited DA D(1) receptor-stimulated cAMP
      formation, but failed to affect either adenosine A(2A) or DA D(2) receptor
      regulation of cAMP. In accumbens slices, N/OFQ inhibited DA D(1)-induced
      phosphorylation of NMDA and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate
      glutamate receptors, whereas in primary cultures of accumbal cells, which were
      found to coexpress NOP and DA D(1) receptors, N/OFQ curtailed DA D(1) receptor
      induced cAMP-response element-binding protein phosphorylation. Thus, in accumbens
      and striatum N/OFQ exerts an inhibitory constraint on DA transmission by acting
      on either pre-synaptic NOP receptors inhibiting TH phosphorylation and DA
      synthesis or post-synaptic NOP receptors selectively down-regulating DA D(1)
      receptor signaling.

PMID- 18717816
TI  - Interaction of caveolin-1, nitric oxide, and nitric oxide synthases in hypoxic
      human SK-N-MC neuroblastoma cells.
AB  - Neuroblastoma cells are capable of hypoxic adaptation, but the mechanisms
      involved are not fully understood. We hypothesized that caveolin-1 (cav-1), a
      plasma membrane signal molecule, might play a role in protecting neuroblastoma
      cells from oxidative injury by modulating nitric oxide (NO) production. We
      investigated the alterations of cav-1, cav-2, nitric oxide synthases (NOS), and
      NO levels in human SK-N-MC neuroblastoma cells exposed to hypoxia with 2% [O2].
      The major discoveries include: (i) cav-1 but not cav-2 was up-regulated in the
      cells exposed to 15 h of hypoxia; (ii) NO donor 1-[N, N-di-(2-aminoethyl) amino]
      diazen-1-ium-1, 2-diolate up-regulated the expression of cav-1, whereas the non
      selective NOS inhibitor N(G)-nitro-L-arginine methyl ester and inducible NOS
      (iNOS) inhibitor 1400W each abolished the increase in cav-1 expression in the
      hypoxic SK-N-MC cells. These results suggest that iNOS-induced NO production
      contributes to the up-regulation of cav-1 in the hypoxic SK-N-MC cells.
      Furthermore, we studied the roles played by cav-1 in regulating NO, NOS, and
      apoptotic cell death in the SK-N-MC cells subjected to 15 h of hypoxic treatment.
      Both cav-1 transfection and cav-1 scaffolding domain peptide abolished the
      induction of iNOS, reduced the production of NO, and reduced the rates of
      apoptotic cell death in the hypoxic SK-N-MC cells. These results suggest that
      increased expression of cav-1 in response to hypoxic stimulation could prevent
      oxidative injury induced by reactive oxygen species. The interactions of cav-1,
      NO, and NOS could be an important signal pathway in protecting the neuroblastoma
      cells from oxidative injury, contributing to the hypoxic tolerance of
      neuroblastoma cells.

PMID- 18717818
TI  - Lactoferrin induces cell surface retention of prion protein and inhibits prion
      accumulation.
AB  - Prion diseases are fatal neurodegenerative disorders, and the conformational
      conversion of normal cellular prion protein (PrP(C)) into its pathogenic,
      amyloidogenic isoform (PrP(Sc)) is the essential event in the pathogenesis of
      these diseases. Lactoferrin (LF) is a cationic iron-binding glycoprotein
      belonging to the transferrin (TF) family, which accumulates in the amyloid
      deposits in the brain in neurodegenerative disorders, such as Alzheimer's disease
      and Pick's disease. In the present study, we have examined the effects of LF on
      PrP(Sc) formation by using cell culture models. Bovine LF inhibited PrP(Sc)
      accumulation in scrapie-infected cells in a time- and dose-dependent manner,
      whereas TF was not inhibitory. Bioassays of LF-treated cells demonstrated
      prolonged incubation periods compared with non-treated cells indicating a
      reduction of prion infectivity. LF mediated the cell surface retention of PrP(C)
      by diminishing its internalization and was capable of interacting with PrP(C) in
      addition to PrP(Sc). Furthermore, LF partially inhibited the formation of
      protease-resistant PrP as determined by the protein misfolding cyclic
      amplification assay. Our results suggest that LF has multifunctional antiprion
      activities.

PMID- 18717819
TI  - Epstein-Barr virus latent membrane protein 2A upregulates UDP-glucose
      dehydrogenase gene expression via ERK and PI3K/Akt pathway.
AB  - The Epstein-Barr virus latent membrane protein 2A (LMP2A) is frequently detected
      in nasopharyngeal carcinoma (NPC), a tumour of high metastatic capacity. A recent
      microarray assay notes that expression of the UDP-glucose dehydrogenase (UGDH)
      gene, participating in glycosaminoglycan synthesis, shows high correlation with
      LMP2A levels in NPC biopsies. This study extends the finding and demonstrates
      that the UGDH transcript and protein quantities, the enzyme activity, and
      glycosaminoglycan contents increase in LMP2A overexpressed human embryonic kidney
      293 (HEK293) cells. The luciferase reporter gene assay demarcates that a region
      from 630 to 486 bp upstream of the transcription start is critical for LMP2A
      mediated gene expression. Moreover, a specificity protein 1 (Sp1) binding site
      mutation in this region reduces the LMP2A-responsive expression of the UGDH gene.
      Consistent with these findings, cell motility enhancement by LMP2A diminishes by
      treating the cells with Sp1-specific inhibitor and small interference RNA
      (siRNA). Using a signalling pathway-specific inhibitor, it is revealed that
      phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated
      kinase (ERK), not c-Jun N-terminal kinase (JNK) and p38, participate in LMP2A
      induced UGDH expression. This study provides a model for molecular mechanism
      participating in LMP2A-mediated UGDH gene activation.

PMID- 18717820
TI  - Clathrin-dependent entry of a gingipain adhesin peptide and Porphyromonas
      gingivalis into host cells.
AB  - Porphyromonas gingivalis, a Gram-negative oral anaerobe, is associated with
      periodontitis, a disease that in some form affects up to 80% of the adult
      population in the USA. The organism interacts with gingival epithelium and
      surrounding tissue, and in this study we analysed interactions initiated by P.
      gingivalis and by a peptide derived from the adhesin domain of arg-gingipain A, a
      member of a family of surface cysteine proteinases. Recombinant peptide A44
      blocked adherence of bacteria to host cell monolayers, and bound to components of
      the cell membrane fraction. In pull-down assays A44 associated with proteins
      involved in a clathrin-dependent endocytosis pathway. Inhibitor studies confirmed
      a role for clathrin, and confocal microscopy demonstrated that both A44-coated
      beads and intact bacteria colocalized with GFP-clathrin in host cells. Finally,
      we used siRNA to determine whether clathrin or caveolin-1 was involved in
      association of peptide and intact bacteria with host cells. Again, the results of
      these assays indicated that association of both A44 and P. gingivalis depended on
      the presence of clathrin, and support a working model in which A44 initiates a
      clathrin-dependent pathway that potentially leads to internalization of peptide
      or bacteria by host epithelial cells.

PMID- 18717821
TI  - Bacterial exotoxins downregulate cathelicidin (hCAP-18/LL-37) and human beta
      defensin 1 (HBD-1) expression in the intestinal epithelial cells.
AB  - Cathelicidin (hCAP-18/LL-37) and beta-defensin 1 (HBD-1) are human antimicrobial
      peptides (AMPs) with high basal expression levels, which form the first line of
      host defence against infections over the epithelial surfaces. The antimicrobial
      functions owe to their direct microbicidal effects as well as the
      immunomodulatory role. Pathogenic microorganisms have developed multiple
      modalities including transcriptional repression to combat this arm of the host
      immune response. The precise mechanisms and the pathogen-derived molecules
      responsible for transcriptional downregulation remain unknown. Here, we have
      shown that enteric pathogens suppress LL-37 and HBD-1 expression in the
      intestinal epithelial cells (IECs) with Vibrio cholerae and enterotoxigenic
      Escherichia coli (ETEC) exerting the most dramatic effects. Cholera toxin (CT)
      and labile toxin (LT), the major virulence proteins of V. cholerae and ETEC,
      respectively, are predominantly responsible for these effects, both in vitro and
      in vivo. CT transcriptionally downregulates the AMPs by activating several
      intracellular signalling pathways involving protein kinase A (PKA), ERK MAPKinase
      and Cox-2 downstream of cAMP accumulation and inducible cAMP early repressor
      (ICER) may mediate this role of CT, at least in part. This is the first report to
      show transcriptional repression of the AMPs through the activation of cellular
      signal transduction pathways by well-known virulence proteins of pathogenic
      microorganisms.

PMID- 18717822
TI  - Functional interactions between anthrax toxin receptors and the WNT signalling
      protein LRP6.
AB  - To exert its activity, anthrax toxin must be endocytosed and its enzymatic toxic
      subunits delivered to the cytoplasm. It has been proposed that, in addition to
      the anthrax toxin receptors (ATRs), lipoprotein-receptor-related protein 6
      (LRP6), known for its role in Wnt signalling, is also required for toxin
      endocytosis. These findings have however been challenged. We show that LRP6 can
      indeed form a complex with ATRs, and that this interaction plays a role both in
      Wnt signalling and in anthrax toxin endocytosis. We found that ATRs control the
      levels of LRP6 in cells, and thus the Wnt signalling capacity. RNAi against ATRs
      indeed led to a drastic decrease in LRP6 levels and a subsequent drop in Wnt
      signalling. Conversely, LRP6 plays a role in anthrax toxin endocytosis, but is
      not essential. We indeed found that toxin binding triggered tyrosine
      phosphorylation of LRP6, induced its redistribution into detergent-resistant
      domains, and its subsequent endocytosis. RNAis against LRP6 strongly delayed
      toxin endocytosis. As the physiological role of ATRs is probably to interact with
      the extracellular matrix, our findings raise the interesting possibility that,
      through the ATR-LRP6 interaction, adhesion to the extracellular matrix could
      locally control Wnt signalling.

PMID- 18717823
TI  - Revealing the pathogenesis of the 5q- syndrome.

PMID- 18717824
TI  - Calcitriol blunts pro-atherosclerotic parameters through NFkappaB and p38 in
      vitro.
AB  - BACKGROUND: Disturbances in vitamin D(3) metabolism are associated with an
      increased cardiovascular morbidity and mortality. The aim of this study was to
      assess the effects of calcitriol, the active metabolite of vitamin D3, on pro
      atherosclerotic parameters in human umbilical vein cord endothelial cells
      (HUVEC). MATERIALS AND METHODS: Calcitriol at 10(-10) and/or 10(-9) mol L(-1) was
      given to cultured HUVEC which were either non-stimulated or lipopolysaccharide
      (LPS) stimulated. Inter cellular adhesion molecule-1 and platelet-endothelial
      cell adhesion molecule-1, were determined by flow cytometry analysis. The
      receptor of advanced glycation end product (RAGE) and interleukin-6 (IL-6) mRNA
      expressions by RT-PCR and IL-6 secretion by enzyme-linked immunosorbent assay
      (ELISA). Nuclear p65 DNA-binding activity was measured by transcription factor
      assay kit and the inhibitor-kappaBalpha (IkappaBalpha), phosphorylated
      IkappaBalpha (P-IkappaBalpha) and phosphorylated-p38 mitogen-activated protein
      kinase (MAPK) protein levels were determined by Western blot. Results Calcitriol
      decreased the adhesion molecules expression, as well as the LPS-induced mRNA
      expressions of RAGE and IL-6 and LPS induced IL-6 secretion. Furthermore, the LPS
      induced nuclear factor kappaB (NFkappaB)-p65 DNA-binding activity was also
      decreased by calcitriol. IkappaBalpha levels were increased and p-IkappaBalpha
      levels decreased after calcitriol treatment. The increased levels of activated
      p38 MAPK after LPS treatment were also decreased due to pre-incubation with
      calcitriol. CONCLUSIONS: The decreased NFkappaB and p38 activities followed by
      calcitriol treatment may explain the anti-inflammatory/atherosclerotic properties
      of calcitriol that were observed previously and were emphasized in this study,
      demonstrating the inhibitory effect of calcitriol on the pro-inflammatory
      parameters: adhesion molecules, RAGE and IL-6.

PMID- 18717825
TI  - Parental diabetes in Taiwanese diabetic women with and without previous
      gestational diabetes.
AB  - Background Gestational diabetes mellitus (GDM) is reported to be associated with
      maternal but not paternal diabetes. This study examined the relative contribution
      of maternal and paternal diabetes among type 2 diabetic women with and without a
      GDM history. Materials and methods A total of 48 502 type 2 diabetic women from a
      national sample were interviewed by telephone. Among them, 510 reported a GDM
      history. Parental diabetes was compared between patients with and without a GDM
      history considering the confounding effects of age, body mass index, smoking,
      hypertension, duration of diabetes and insulin use. Results Patients with a GDM
      history were younger in age, had younger age of onset, longer duration of
      diabetes, slightly lower body mass index, higher prevalence of insulin use and
      lower prevalence of hypertension, but smoking rates were similar. The percentages
      of parental diabetes of nil, mother only, father only and both father and mother
      for those without a GDM history were 76.2, 15.2, 5.8 and 2.8%, respectively; and
      were 47.8, 26.8, 17.5 and 7.9%, respectively, for those with a GDM history (P <
      0.001). The adjusted odds ratios for patients with versus without a GDM history
      for parental diabetes of nil, mother only, father only, and both father and
      mother were 1.000, 1.210 (0.948-1.544), 1.783 (1.341-2.371) and 2.094 (1.440
      3.045), respectively. Conclusions Although maternal diabetes is more commonly
      seen, the disproportionately higher paternal diabetes in patients with a GDM
      history suggests an important role for paternal diabetes on the development of
      GDM into type 2 diabetes mellitus.

PMID- 18717826
TI  - Cardiac and kidney hormones cure up to 86% of human small-cell lung cancers in
      mice.
AB  - BACKGROUND: Four cardiac hormones synthesized by the same gene, i.e. atrial
      natriuretic peptide, vessel dilator, long acting natriuretic peptide and
      kaliuretic peptide, and the kidney hormone urodilatin have anticancer effects in
      vitro. MATERIALS AND METHODS: These cardiac hormones and urodilatin were infused
      subcutaneously for 28 days with weekly fresh hormones since they lose biological
      effects at body temperature for more than a week at 0.3 nm kg(-1) body weight in
      athymic mice bearing human small-cell lung carcinomas. RESULTS: Long acting
      natriuretic peptide, vessel dilator, kaliuretic peptide, atrial natriuretic
      peptide and urodilatin eliminated 86%, 71%, 57%, 43% (P < 0.001 for the cardiac
      hormones) and 25% (P < 0.05; urodilatin) of the human small-cell lung carcinomas.
      The treated small-cell lung carcinomas that were not cured grew rapidly, similar
      to the untreated controls, whose volume was 7 fold larger in 1 week, 18-fold
      increased in 2 weeks, 39-fold increased in 3 weeks, 63-fold increased in 1 month
      and 97-fold increased in volume in 6 weeks. One vessel dilator treated small-cell
      lung carcinoma animal developed a large tumour (8428 mm3 volume) on treatment and
      this tumour was eliminated with utilizing atrial natriuretic peptide and then
      long acting natriuretic peptide sequentially. CONCLUSIONS: Four cardiac hormones
      eliminate up to 86% of human small-cell lung carcinomas in athymic mice.
      Urodilatin can also eliminate small-cell lung carcinomas but at a lower cure rate
      of 25%. Unresponsive lesions can be eliminated by utilizing different hormones
      synthesized by the atrial natriuretic peptide gene in a sequential manner.

PMID- 18717827
TI  - Dasatinib inhibits progenitor cell proliferation from polycythaemia vera.
AB  - BACKGROUND: A mutation of Janus kinase 2 V617F is present in most patients with
      polycythaemia vera (PV). However, it is generally believed that JAK2(V617F) is
      not the sole molecular abnormality in PV. Since dasatinib is currently evaluated
      in patients with PV, it is of interest to study the effects of dasatinib on the
      growth of clonal progenitor cells in vitro. DESIGN AND METHODS: Peripheral blood
      mononuclear cells from patients with PV, chronic myeloid leukaemia (CML) and
      controls were exposed to dasatinib (0.1 to 500 nm mL(-1)). Colony growth was
      stimulated by interleukin-3, granulocyte-macrophage colony-stimulating factor and
      erythropoietin. Endogenous erythroid colony (EEC) growth was investigated without
      exogenous cytokines. Real-time PCR was performed to assess the percentage of
      JAK2(V617F) cells. RESULTS: 10 nm of dasatinib suppressed EEC growth from PV by
      89% (P = 0.002). This inhibition was dose dependent and occurred at
      pharmacological concentrations. Erythroid and myeloid colony growth was also
      significantly suppressed in the presence of exogenous cytokines. When compared to
      PV the inhibition of stimulated colony growth was significantly less pronounced
      in controls but tended to be more vigorous in CML. Interestingly, despite the
      potent inhibition of PV cells real-time PCR revealed that the numbers of
      JAK2(V617F) transcripts did not decrease upon exposure to dasatinib. CONCLUSION:
      This study shows a marked inhibition of the proliferative capacity of progenitor
      cells from PV. Although JAK2(V617F) transcript levels did not decrease upon
      exposure to dasatinib, the drug might suppress PV progenitors through inhibition
      of a yet undefined molecular target.

PMID- 18717828
TI  - Chronic aspiration shifts the immune response from Th1 to Th2 in a murine model
      of asthma.
AB  - BACKGROUND: Chronic aspiration associated with gastro oesophageal reflux disease
      (GERD) is thought to play a substantial role in the development of asthma, the
      incidence of which is dramatically increasing in industrially developed
      countries. The majority of data examining the association between aspiration and
      asthma has been obtained from epidemiological studies, which show that between 50
      and 90% of individuals with asthma experience some element of GERD. This study
      describes the effect of chronic aspiration on a model of experimentally induced
      airway hypersensitivity in Balb/c mice. MATERIALS AND METHODS: Four experimental
      groups were utilized: Aspiration/Asthma, Sham/Asthma, Aspiration/Sham and
      Sham/Sham. Mice were sensitized with aerosolized 1% ovalbumin on days 1 to 10
      (sensitization phase), followed by repeated exposure on days 31 to 40 (challenge
      phase). Aspiration events occurred on days 1, 8,15, 22, 29, 36, 43 and 50.
      Animals were sacrificed on days 56 and 57. RESULTS: Chronic aspiration of 10
      microL of murine gastric fluid per week for eight weeks produced an injury
      pattern distinct from that of acute aspiration, with lung injury characterized by
      hyperplasia, neutrophil infiltration of the bronchioles and relative parenchymal
      sparing. Aspiration during induction of ovalbumin-induced airway hypersensitivity
      was associated with a trend toward decreased production of antiovalbumin IgG,
      antiovalbumin IgE, and total IgE. Further, aspiration induced a substantial and
      significant increase in antiovalbumin IgG1/IgG2a ratios, consistent with a shift
      toward a predominantly Th2 response. CONCLUSION: These findings indicate that
      chronic aspiration has a profound effect on the nature of the immune response to
      aerosolized allergens in a model of experimentally induced airway
      hypersensitivity.

PMID- 18717829
TI  - A case of Cogan's syndrome resolved with mycophenolate sodium.

PMID- 18717830
TI  - Guest editorial: on inconvenient truths.

PMID- 18717831
TI  - The influence of ceramic surface treatments on the micro-shear bond strength of
      composite resin to IPS Empress 2.
AB  - PURPOSE: An increasing demand for esthetic restorations has resulted in the
      development of new ceramic systems, but fracture of veneering ceramics still
      remains the primary cause of failure. Porcelain repair frequently involves
      replacement with composite resin, but the bond strength between composite resin
      and all-ceramic coping materials has not been studied extensively. The purpose of
      this study was to evaluate the influence of different ceramic surface treatments
      on the micro-shear bond strength of composite resin to IPS Empress 2 coping
      material. MATERIALS AND METHODS: Sixteen 7 x 7 x 1 mm(3) lithia disilicate-based
      core ceramic plates were fabricated using the lost wax technique. The plates were
      divided into eight groups, and eight different surface treatments were performed:
      (1) no treatment (NT); (2) airborne-particle abrasion with 50-mum alumina
      particles (Al); (3) acid etching with 9.6% hydrofluoric acid for 1 min (HF); (4)
      silane coating (S); (5) AlHF; (6) AlS; (7) HFS; and (8) AlHFS. Then, ten
      composite resin cylinders (0.8-mm diameter x 0.5-mm height) were light
      polymerized onto the ceramic plates in each group. Each specimen was subjected to
      a shear load at a crosshead speed of 0.5 mm/min until fracture occurred. The
      fracture sites were examined with scanning electron microscopy (SEM) to determine
      the location of failure during debonding and to examine the surface treatment
      effects. One-way analysis of variance (ANOVA) and multiple comparison (Dunnet T3)
      tests were used for statistical analysis of data. RESULTS: The mean micro-shear
      bond strength values (SD) in MPa were--NT: 4.10 (3.06), Al: 7.56 (4.11), HF:
      14.04 (2.60), S: 14.58 (2.14), AlHF: 15.56 (3.36), AlS: 23.02 (4.17), HFS: 24.7
      (4.43), AlHFS: 26.0 (3.71). ANOVA indicated the influence of surface treatment
      was significant (p < 0.0001). SEM analysis did not reveal entirely cohesive
      failure in any composite or ceramic. CONCLUSION: The micro-shear bond strength of
      a composite resin to IPS Empress 2 was significantly different depending on the
      surface treatment method. Among the investigated methods, silane coating after
      airborne-particle abrasion and etching was the most effective surface treatment
      in terms of bond strength increase.

PMID- 18717832
TI  - Get patients to keep their appointments.

PMID- 18717834
TI  - Abstracts of the 48th Annual Meeting of the Society for Psychophysiological
      Research, October 1-5, 2008, Austin, Texas, USA.

PMID- 18717854
TI  - Sweet's syndrome with hematologic disorders: a review and reappraisal.

PMID- 18717855
TI  - Clinicopathologic challenge. Gangrenous cellulitis caused by Peptostreptococcus.

PMID- 18717856
TI  - Xanthelasma palpebrarum and its relation to atherosclerotic risk factors and
      lipoprotein (a).
AB  - OBJECTIVES: To investigate the association between xanthelasma, atherosclerotic
      risk factors, and lipoprotein (Lp) (a), and to determine whether xanthelasma may
      be a cutaneous marker for atherosclerosis. METHODS: One hundred consecutive
      patients with xanthelasma and 100 age- and sex-matched patients without
      xanthelasma, seen during the same time period (controls), were included in this
      study. The prevalence of cardiac risk factors, the rates of atherosclerotic
      disease, Framingham risk scores, and Lp (a) levels were compared between the
      patient groups. RESULTS: Hyperlipidemia was found to be significantly more common
      in patients with xanthelasma (P = 0.001); however, the rate of clinically overt
      cardiovascular disease and future cardiovascular risk, assessed by the Framingham
      risk score, were similar between the groups. No significant difference was
      observed in serum Lp (a) levels between the groups. CONCLUSIONS: In patients with
      xanthelasma, no increase was observed in the rate or risk of cardiovascular
      disease. Moreover, no relationship was found between Lp (a) levels and
      xanthelasma.

PMID- 18717858
TI  - Dermoscopic findings in frontal fibrosing alopecia: report of four cases.
AB  - BACKGROUND: Frontal fibrosing alopecia (FFA) is characterized by frontotemporal
      hair recession and eyebrow loss and by a histopathology identical to lichen
      planopilaris. Differential diagnosis from other types of alopecia, including
      alopecia areata (AA), is necessary in some cases. OBJECTIVE: To describe
      dermoscopic findings of FFA and to investigate the possibility of utilizing
      dermoscopy as a diagnostic tool for FFA. METHODS: Four cases of FFA diagnosed by
      clinical and/or histological findings were examined by dermoscopy. RESULTS: The
      loss of orifices, perifollicular erythema or scale was seen in all the four cases
      (4/4), in three cases (3/4) or in two cases (2/4), respectively. None of the
      cases showed yellow dots characteristic of AA. Immunohistochemistry showed T
      lymphocyte infiltration into the infundibulum and isthmus. CONCLUSION: Dermoscopy
      is a helpful diagnostic tool for FFA especially to distinguish it from AA.

PMID- 18717857
TI  - House dust mites on skin, clothes, and bedding of atopic dermatitis patients.
AB  - BACKGROUND: Atopic dermatitis is a common allergic condition in children, often
      associated with a positive skin reaction to house dust mite allergens. AIM: To
      determine the presence of house dust mites on the skin, clothes, and bedding of
      patients with atopic dermatitis. METHODS: Nineteen patients with atopic
      dermatitis were examined during a 2-year period. Samples from affected and
      healthy skin surfaces were obtained with adhesive tape, and dust samples from
      bedding and clothes were collected with a vacuum cleaner at the start of the
      study and 3-6 weeks later, and examined for the presence of house dust mites. The
      findings were compared with those of 21 healthy controls. RESULTS: The most
      common mite species on skin were Dermatophagoides pteronyssinus and
      Dermatophagoides farinae, which were found in nine patients and three controls.
      The patient group showed a significantly larger percentage of samples with mites
      than did the control group (34.9% and 7.9%, respectively) (P < 0.001), and a
      significantly larger percentage of individuals with at least one positive sample
      (84.2% and 14.2%, respectively) (P < 0.0001). No correlation was found between
      the number of mites on the skin and clothes/bedding of patients, or between
      patients and controls with regard to the number of mites on the clothes and
      bedding. CONCLUSIONS: Patients with atopic dermatitis showed a higher prevalence
      of mites on their skin than did healthy individuals, which could be involved in
      allergic sensitization and disease exacerbation.

PMID- 18717859
TI  - Serum levels of the pro-inflammatory cytokine interleukin-12 and the anti
      inflammatory cytokine interleukin-10 in patients with psoriasis treated by the
      Goeckerman regimen.
AB  - BACKGROUND: The Goeckerman regimen (GR) involves the dermal application of a
      crude coal tar (polycyclic aromatic hydrocarbon, PAH) and exposure to ultraviolet
      (UV) radiation. Both PAH and UV radiation exhibit immunosuppressive activity.
      This study describes the changes in the serum levels of the pro-inflammatory
      cytokine interleukin-12 (IL-12) and the anti-inflammatory cytokine IL-10 in
      patients with psoriasis (n = 55) treated with GR. METHODS: The serum levels of IL
      12 and IL-10 were compared before and after GR. In addition, the IL-12 and IL-10
      levels in psoriatic patients were compared with those in a control group of
      healthy blood donors (n = 47). The Psoriasis Area and Severity Index (PASI) was
      used to evaluate the efficacy of GR. RESULTS: When compared with the control
      group, both IL-12 and IL-10 were significantly higher in psoriatic patients in
      all cases (P < 0.001). When compared before and after GR, the IL-12 and IL-10
      levels (P < 0.01) and PASI value (P < 0.001) were significantly lower after GR.
      The decrease in the serum level of IL-12 and IL-10 after GR was related to the
      entry value before GR (IL-12, r = 0.60, P < 0.001; IL-10, r = 0.36, P < 0.01).
      There was a significant correlation between the IL-10 level before GR and the
      PASI value after GR (r = -0.39; P < 0.01). CONCLUSIONS: The results indicate a
      strong pro-inflammatory effect of IL-12 in the immunopathogenesis of psoriasis,
      and confirm the immunosuppressive and anti-inflammatory effect of GR. IL-10 seems
      to be a promising individual marker for a positive effect of GR therapy.

PMID- 18717861
TI  - Ceramide 1 and ceramide 3 act synergistically on skin hydration and the
      transepidermal water loss of sodium lauryl sulfate-irritated skin.
AB  - BACKGROUND: Stratum corneum intercellular lipids, such as ceramides, play an
      important role in the regulation of skin water barrier homeostasis and water
      holding capacity. Aim To evaluate the potential water retention capacity of
      control emulsion and three oil-in-water (o/w) emulsions containing ceramide 1,
      ceramide 3, or both. METHODS: Fifteen healthy Asian women (age, 20-30 years) with
      healthy skin, pretreated with sodium lauryl sulfate (SLS), applied the tested
      emulsions twice daily over a period of 28 days. Skin hydration and transepidermal
      water loss (TEWL) values were measured on the indicated days with a
      Corneometer(R)825 and a TEWAMETER TM210, respectively. RESULTS: The maximum
      increase in skin humidity was reached after 4 weeks, with values of 21.9 +/- 1.8%
      and 8.9 +/- 0.9% for emulsion C and control emulsion, respectively. The maximum
      decrease in TEWL was also reached after 4 weeks, with values of 36.7 +/- 4.7% and
      5.1 +/- 0.8% for the same emulsions. CONCLUSIONS: It can be concluded that all
      the tested ceramide-containing emulsions improved skin barrier function when
      compared with untreated skin. There was some indication that ceramides 1 and 3
      contained in emulsion C might exert a beneficial synergistic effect on skin
      biochemical properties, such as skin hydration and TEWL, and play a key role in
      the protection mechanism against SLS irritation.

PMID- 18717860
TI  - Main pigmentary features and melanocortin 1 receptor (MC1R) gene polymorphisms in
      the population of the Canary Islands.
AB  - BACKGROUND: Sun exposure, light skin pigmentation, and melanocortin 1 receptor
      (MC1R) gene variants are independent risk factors for skin cancer. The Canary
      Islands have a sunny and temperate climate, but data regarding the phenotypic and
      genotypic risk factors among the population are lacking. METHODS: The main
      phenotypic features (skin color, hair color, eye color, and freckling) of 5116
      healthy individuals are described. The genotypic findings of six MC1R gene
      variants (V60L, D84E, R150C, R160W, R163Q, and T314T) in 116 healthy individuals
      from a population-based cohort with at least three generations of Canary Islands'
      ancestry are evaluated. The variants were analyzed by SNaPshot. RESULTS: Fifty
      per cent of the population showed at least one phenotypic risk factor (fair skin,
      34.3%; freckling, 17.4%; green or blue eyes, 16.8%; red or blonde hair, 7.8%),
      although brown skin (65.7%), dark eyes (83.2%), and dark hair (92.2%) prevailed.
      Forty-three per cent of the individuals showed at least one of the MC1R variants
      studied. Allelic frequencies for V60L, D84E, R150C, R160W, R163Q, and T314T were
      9.1%, 1.7%, 3.0%, 0.8%, 3.0%, and 8.2%, respectively. CONCLUSION: A significant
      proportion of the population showed risk factors for skin cancer. The inhabitants
      of the Canary Islands are phenotypically and genotypically close to Mediterranean
      populations.

PMID- 18717862
TI  - The diagnosis of two cases of cutaneous ulcer caused by infection with
      Mycobacterium haemophilum: direct identification in a clinical sample by
      polymerase chain reaction-restriction endonuclease analysis.
AB  - BACKGROUND: Mycobacterium haemophilum was first recovered from subcutaneous
      lesions of a patient with Hodgkin's disease. Because of its special growth
      requirements (it grows at 30-32 degrees C and requires iron-supplemented medium),
      the organism cannot be isolated using routine culture techniques for other
      mycobacteria. Only a few developed countries have reported infection with this
      mycobacterium. We report the first two cases diagnosed in Venezuela. METHODS: The
      diagnosis of the first case was established using polymerase chain reaction (PCR)
      restriction endonuclease analysis of the gene encoding the 65-kDa heat shock
      protein (hsp65) for the direct identification of M. haemophilum in a clinical
      specimen in which bacilli were observed on acid-fast smear, but growth was not
      detected by standard culture procedures. RESULTS: After recognizing this
      bacterium as a possible cause of infection in our setting, clinical samples of
      cutaneous lesions were routinely cultured on blood agar at 30 degrees C for at
      least 6 weeks, which resulted in the diagnosis of the second case. CONCLUSIONS:
      Dermatologists should consider this bacterium in immunocompromised patients with
      cutaneous ulcerating lesions. Material from the lesions can be screened for
      mycobacteria using an acid-fast stain and, if acid-fast bacilli are seen, PCR
      analysis of mycobacterial hsp65 can be an effective tool for early diagnosis.
      Appropriate culture methods are required for bacteriologic confirmation of
      infection with M. haemophilum.

PMID- 18717863
TI  - Cutaneous blastomycosis: a diagnostic challenge.
AB  - Primary cutaneous inoculation blastomycosis occurs less commonly than secondary
      blastomycosis, in which cutaneous lesions most often originate from a primary
      pulmonary infection which disseminates through the blood or lymphatics to involve
      the skin. In secondary cutaneous blastomycosis, the primary pulmonary infection
      is frequently subclinical at the time cutaneous lesions manifest. Here we report
      two cases that illustrate the difficulty in distinguishing between primary and
      secondary cutaneous involvement. We also review the expanding literature on
      blastomycosis since its identification over a century ago.

PMID- 18717864
TI  - Vulvar pruritus caused by syringoma of the vulva.

PMID- 18717865
TI  - Primary cutaneous inoculation tuberculosis in a healthcare worker as a result of
      a surgical accident.
AB  - In May 2004, a 48-year-old male surgeon, resident in Bucaramanga, Colombia,
      suffered a superficial cut with a scalpel to the lateral aspect of the mid
      phalanx of the second finger of the left hand while performing a pulmonary
      decortication surgical procedure for tuberculous empyema with pulmonary
      entrapment. The injury healed normally but, approximately 2 weeks after the
      event, an erythematous, nonpainful papule of approximately 3 mm in diameter
      developed, and increased progressively to 7 mm 3 days after its initial
      appearance. At this time, the papule showed spontaneous secretion of a clear
      liquid and superficial ulceration (Fig. 1). Approximately 3 weeks after the
      injury, a Gram stain of the liquid was performed; it showed no bacteria but a
      moderate leukocyte reaction. Because of the high suspicion of possible
      tuberculous infection, bacilloscopy of the liquid was performed, and was positive
      (++) for acid-fast bacteria (Fig. 2). The liquid was cultured and grew
      Mycobacterium tuberculosis. The culture was sent to the Laboratory of
      Mycobacteria at the National Institute of Health, Bogota, Colombia for drug
      resistance testing. Susceptibility was demonstrated against streptomycin,
      isoniazid, rifampicin, and ethambutol. During this time, the patient presented an
      ipsilateral painful axillary adenopathy of about 2.5 cm in diameter. The patient
      consulted with an infectologist, who initiated a Directly Observed Therapy Short
      Course (DOTS) regimen [first phase (8 weeks): daily, except Sundays, streptomycin
      1 g intramuscularly, pyrazinamide 1500 mg orally, isoniazid 300 mg, and
      rifampicin 600 mg; second phase (18 weeks): twice weekly rifampicin 600 mg and
      isoniazid 500 mg], accompanied by daily pyridoxine to prevent secondary effects
      from isoniazid. After 3 weeks of treatment, the finger lesion had disappeared.
      Treatment was undertaken as described above, with the patient reporting symptoms
      of vertigo, nausea, epigastralgia, and mild myalgia as the adverse effects of
      medication. A chest x-ray was taken and reported to be normal. The axillary
      adenopathy disappeared approximately 6 months after the injury. Nearly 3.5 years
      after the incident, the patient has not presented any type of symptomatology.

PMID- 18717866
TI  - HIV-seropositive patient with Sweet's syndrome and nodular scleritis, showing
      dramatic response after adding dapsone to systemic corticosteroid therapy.

PMID- 18717867
TI  - Rabson-Mendenhall syndrome.
AB  - Rabson mendenhall syndrome is a rare autosomally recessive inherited insulin
      resistant disorder. This is characterized by growth retardation, dysmorphisms,
      lack of subcutaneous fat, acanthosis nigricans, enlarged genitalia
      hypertrichosis, premature and dysplastic dentition, coarse facial features,
      paradoxical fasting hypoglycemia and postprandial hyperglycemia, extreme
      hyperinsulinemia, protracted course, and eventual development of ketoacidosis. We
      report a male patient with all the features of Rabson-Mendenhall syndrome from
      our institute.

PMID- 18717868
TI  - A case of Sweet's syndrome with slack skin and pathergy phenomenon.

PMID- 18717869
TI  - Tibialis anterior muscle herniation developed after trauma.

PMID- 18717870
TI  - Surgical pearl: a simple means of disarming the "locked and loaded" needle.
AB  - BACKGROUND: Surgery, in any setting, has several inherent risks not only to the
      patient, but the physician and his assistants as well. Safe handling and
      management of the sharps to prevent inoculation injuries is one of these risks,
      in particular: 1) instrument hand-off of the needle and needle driver between the
      physician and his assistants; 2) retrieval of instruments from the surgical tray.
      OBJECTIVE: The authors' review a simple means of disarming the needle loaded in
      the needle driver to reduce sharps injury. METHODS: Before the needle and needle
      driver are either handed off to the assistant or returned to the surgical tray,
      pivot the needle 90 degrees toward the instrument joint. The needle's point
      should be directed toward and touching the needle driver, and thereby, disarming
      the needle. To avoid dulling the needle, the point should not be grasped by the
      needle driver. CONCLUSIONS: Disarming the loaded needle may reduce the chance of
      sharps injury during instrument hand off and retrieving instruments from the
      surgical tray.

PMID- 18717871
TI  - Treatment of persistent alopecia areata with sulfasalazine.
AB  - BACKGROUND: Alopecia areata is an autoimmune disease with no definitive
      treatment, and some cases persist despite standard therapies. Sulfasalazine has
      been reported to show success in the treatment of persistent cases of alopecia
      areata. Objective To assess the efficacy of sulfasalazine in cases of
      recalcitrant alopecia areata that do not respond to topical and intralesional
      corticosteroids, 5% minoxidil, or psoralen plus ultraviolet-A (PUVA) therapy.
      METHODS: Thirty-nine patients with persistent alopecia areata received 3 g of
      oral sulfasalazine for 6 months, and terminal hair regrowth was quantified as no
      response, moderate response, or good response. RESULTS: A good response occurred
      in 10 of the 39 patients (25.6%), a moderate response in 12 (30.7%), and a poor
      or no response in 17 (43.5%). CONCLUSION: Sulfasalazine can be used as an
      alternative drug in patients with persistent alopecia areata.

PMID- 18717872
TI  - Carbamazepine-induced drug reaction with eosinophilia and systemic symptoms
      (DRESS) syndrome: report of four cases and brief review.
AB  - Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare
      but severe drug reaction, most commonly to aromatic anticonvulsants with a
      delayed onset, variable clinical presentation and protracted course. The exact
      incidence of DRESS syndrome is not known because of the variability in clinical
      presentation, lack of strict diagnostic criteria and universally accepted
      nomenclature. We report four cases of DRESS syndrome associated with the use of
      carbamazepine. The clinical manifestation was similar: a maculopapular eruption
      progressing to exfoliative erythroderma, fever, and lymphadenopathy.
      Leukocytosis, atypical lymphocytes and liver injury (in 2 patients) were also
      observed. Assessment of causality using the Naranjo algorithm established a
      "probable" relationship with carbamazepine in three of the cases and a "possible"
      relationship in one case. Detection of DRESS syndrome is dependent on the
      exclusion of a variety of diseases with similar manifestations and may be delayed
      in time. DRESS syndrome is a potentially life-threatening multisystem adverse
      drug reaction, and accidental reexposure or drug provocation tests must be
      avoided.

PMID- 18717873
TI  - Onset and duration of action of topical antihistamine: a study of histamine skin
      test response.
AB  - BACKGROUND: Most patients who require skin prick testing cannot deal with their
      pruritus without taking antihistamines (AH). Orally administered AH has a quick
      onset of action, but it will suppress skin test responses (STR) from several days
      to weeks. In this study, we aimed to determine the onset and duration of action
      of single topical AH application by observing histamine-STR suppression over
      time. METHODS: A two-step, randomized, intraindividual parallel-comparative,
      double-blind, placebo-controlled trial was conducted on the volar side of the
      forearm. Step 1 was aimed to determine the onset, while step 2 determined the
      duration of action. The topical AH tested was a single application of 5% doxepin
      hydrochloride cream, while 10 mg/ml histamine dihydrochloride was used to test
      the skin responses. RESULTS: Our 10 subjects' mean age was 35.8 +/- 3.179 years.
      Histamine wheal response was suppressed starting on minute 90 and the wheal width
      were back to >/= 7 mm(2 )on minute 270. Significant histamine reactivity
      difference between genders (P = 0.201) and atopic status (P = 1.000), which could
      be a source of bias in histamine STR, was not found among our subjects.
      CONCLUSION: Single application of topical AH has an onset of action in 90 min and
      duration of action < 180 min. Because of its short duration of action, topical AH
      can be used in a patient who needs AH but is scheduled to undergo skin prick
      testing after a few hours, without influencing the patient's STR.

PMID- 18717874
TI  - A case of patchy alopecia areata sparing lesional greying hairs.

PMID- 18717875
TI  - Influence of the human activity in the Atlantic Forest and in the prevalence of
      etiological agents of dermatophytosis in a coastal city of Southern Brazil
      [Ubatuba (Sao Paulo)].

PMID- 18717876
TI  - Interaction between BCL2 and JUNB in primary cutaneous lymphoma: a gene ontology
      approach.

PMID- 18717877
TI  - Saline irrigation to facilitate unfolding of selected full-thickness skin grafts.

PMID- 18717878
TI  - Youngest case of idiopathic calcinosis cutis not associated with Down syndrome.

PMID- 18717879
TI  - Necrolytic acral erythema successfully treated with oral zinc.

PMID- 18717880
TI  - Endogenous ochronosis with a predominant acrokeratoelastoidosis-like
      presentation.

PMID- 18717884
TI  - Assessment of the stability of cell-surface components of microorganisms by MALDI
      TOF-MS following preservation on lenticule discs.
AB  - Strains representing the species Campylobacter coli, Escherichia coli, Listeria
      monocytogenes, Pseudomonas aeruginosa, Salmonella enterica, and Staphylococcus
      aureus were randomly selected to assess the consistency of cells preserved on
      lenticule discs to those archived in traditional freeze-dried ampoules. Each
      matched pair was cultured using identical conditions and analysed by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MS) to
      profile the surface-associated molecules of the cells. In addition, the
      cytosolic/membrane-bound proteins of C. coli and S. aureus strains were further
      analysed by surface-enhanced laser desorption/ionization time-of-flight MS. The
      mass spectral profiles in all cases showed a high degree of concordance between
      cells preserved by both methods and suggest that the properties of cells
      preserved on lenticule disc are consistent with those archived by the traditional
      method of freeze-drying.

PMID- 18717887
TI  - Response to 'HIV vaccine trials: reconsidering the therapeutic misconception and
      the question of what constitutes trial-related injuries'.

PMID- 18717891
TI  - Congruency as a nonspecific perceptual property contributing to newborns' face
      preference.
AB  - Past research has shown that top-heaviness is a perceptual property that plays a
      crucial role in triggering newborns' preference toward faces. The present study
      examined the contribution of a second configural property, congruency, to
      newborns' face preference. Experiments 1 and 2 demonstrated that when embedded in
      nonfacelike stimuli, congruency induces a preference of the same strength as that
      induced by facedness. Experiments 3 and 4 demonstrated that the attentional
      biases toward facedness and congruency produce a cumulative effect on newborns'
      visual preferences according to an additive model. These findings were extended
      by those of Experiment 5, showing that the additive model holds true when
      congruency is added to top-heaviness in nonfacelike stimuli displaying more
      elements in the upper portion.

PMID- 18717892
TI  - Grown-ups are not afraid of scary stuff, but kids are: young children's and
      adults' reasoning about children's, infants', and adults' fears.
AB  - Three-, 5-, and 7-year-olds and adults (N= 64) listened to stories depicting 2
      protagonists of different ages (infant and child or child and grown-up) that
      encounter an entity that looks like a real (e.g., a snake) or an imaginary (e.g.,
      a ghost) fear-inducing creature. Participants predicted and explained each
      protagonist's intensity of fear. Results showed significant age-related increases
      in knowledge that infants and adults would experience less intense fears than
      young children and that people's fears are causally linked to their cognitive
      mental states. Across age, stories involving imaginary beings elicited more
      frequent mental explanations for fear than stories about real creatures. Results
      are discussed in relation to children's developing awareness of the mind as
      mediating between situations and emotions.

PMID- 18717893
TI  - Gender and patterns of concerned responsiveness in representations of the mother
      daughter and mother-son relationship.
AB  - Given that girls show more interpersonal concern than boys, it was predicted that
      more mother-daughter than mother-son dyads would develop a relationship of mutual
      concerned responsiveness (CR). Two hundred and twenty-six Israeli children (7-8
      years old) and 91 mother-child pairs provided narratives of mother-child
      interactions. At high levels of socioeconomic status (SES), descriptions of child
      but not maternal concern differed by gender; therefore, more mother-daughter
      narratives described mutual CR and more mother-son narratives described a
      nonreciprocal pattern of maternal CR. In a low-SES sample, most mother-daughter
      narratives described mutual CR, but many mothers and sons described little
      concern by either partner. Results provided clear evidence of gender differences
      in mother-child reciprocity and confirmed the importance of examining gender
      influences in different social groups.

PMID- 18717894
TI  - Development of feedforward control in a dynamic manual tracking task.
AB  - To examine the development of feedforward control during manual tracking, 117
      participants in 5 age groups (6 to 7, 8 to 9, 10 to 11, 12 to 14, and 15 to 17
      years) tracked an accelerating dot presented on a monitor by moving an electronic
      pen on a digitizer. To remain successful at higher target velocities, they had to
      create a predictive model of the target's motion. The ability to track the target
      at higher velocities increased, and the application of a feedback-based step-and
      hold strategy decreased with age, as shown by increases in maximum target
      velocity and decreases in number of stops between ages 6-7 and 8-9 and between
      ages 8-9 and 10-11. The ability to exploit feedforward control in a dynamic
      tracking task improves significantly with age.

PMID- 18717895
TI  - Social and cognitive correlates of children's lying behavior.
AB  - The relation between children's lie-telling and their social and cognitive
      development was examined. Children (3-8 years) were told not to peek at a toy.
      Most children peeked and later lied about peeking. Children's subsequent verbal
      statements were not always consistent with their initial denial and leaked
      critical information revealing their deceit. Children's conceptual moral
      understanding of lies, executive functioning, and theory-of-mind understanding
      were also assessed. Children's initial false denials were related to their first
      order belief understanding and their inhibitory control. Children's ability to
      maintain their lies was related to their second-order belief understanding.
      Children's lying was related to their moral evaluations. These findings suggest
      that social and cognitive factors may play an important role in children's lie
      telling abilities.

PMID- 18717896
TI  - Moral development in a violent society: Colombian children's judgments in the
      context of survival and revenge.
AB  - Ninety-six Colombian children (mean age = 7.7 years) and adolescents (mean age =
      14.6 years) made judgments about stealing and physical harm in the abstract and
      in the context of survival and revenge. All participants judged it wrong to steal
      or hurt others because of considerations with justice and welfare, and most also
      judged it wrong to engage in such actions even when they can aid in survival.
      Their judgments in the context of revenge were more mixed, with a sizable
      proportion endorsing stealing and hurting in that condition. Furthermore, the
      majority expected that people would steal and hurt others in most situations.
      Significant age differences were also found. The consequences of political
      violence for moral development are discussed.

PMID- 18717897
TI  - Pathways to literacy: a study of invented spelling and its role in learning to
      read.
AB  - This intervention study tested whether invented spelling plays a causal role in
      learning to read. Three groups of kindergarten children (mean age = 5 years 7
      months) participated in a 4-week intervention. Children in the invented-spelling
      group spelled words as best they could and received developmentally appropriate
      feedback. Children in the 2 comparison groups were trained in phonological
      awareness or drew pictures. Invented-spelling training benefited phonological and
      orthographic awareness and reading of words used in the intervention.
      Importantly, the invented-spelling group learned to read more words in a learn-to
      read task than the other groups. The finding are in accord with the view that
      invented spelling coupled with feedback encourages an analytical approach and
      facilitates the integration of phonological and orthographic knowledge, hence
      facilitating the acquisition of reading.

PMID- 18717898
TI  - Coaching, truth induction, and young maltreated children's false allegations and
      false denials.
AB  - This study examined the effects of coaching (encouragement and rehearsal of false
      reports) and truth induction (a child-friendly version of the oath or general
      reassurance about the consequences of disclosure) on 4- to 7-year-old maltreated
      children's reports (N = 198). Children were questioned using free recall,
      repeated yes-no questions, and highly suggestive suppositional questions.
      Coaching impaired children's accuracy. For free-recall and repeated yes-no
      questions, the oath exhibited some positive effects, but this effect diminished
      in the face of highly suggestive questions. Reassurance had few positive effects
      and no ill effects. Neither age nor understanding of the meaning and negative
      consequences of lying consistently predicted accuracy. The results support the
      utility of truth induction in enhancing the accuracy of child witnesses' reports.

PMID- 18717899
TI  - Genetic influences on activity level in early childhood: do situations matter?
AB  - Although genetic influences on individual differences in activity level (AL) are
      well documented, few studies have considered the etiology of AL from a contextual
      perspective. In the present study, cross-situational and context-specific genetic
      effects on individual differences in AL at age 2 were examined. The AL of 312
      twin pairs (144 monozygotic and 168 dzygotic) was mechanically assessed with
      actigraphs in the home and in laboratory test and play situations. AL displayed
      significant genetic variance in all 3 situations. Moreover, actigraph scores
      significantly correlated across situations. Multivariate genetic model-fitting
      analyses found that the observed cross-situational continuity in AL was due
      entirely to genetic factors. Situational differences in AL arise from genetic,
      shared environmental, and nonshared environmental influences.

PMID- 18717900
TI  - Stability and change in ethnic labeling among adolescents from Asian and Latin
      American immigrant families.
AB  - An important question for the acculturation of adolescents from immigrant
      families is whether they retain ethnic labels that refer to their national origin
      (e.g., Mexican, Chinese) or adopt labels that are dominant in American society
      (e.g., Latino, Asian American, American). Approximately 380 adolescents from
      Asian and Latin American immigrant families selected ethnic labels during each of
      the 4 years of high school (age span = 14.87-17.82 years). Results indicated no
      normative trend either toward or away from identifying most closely with pan
      ethnic or American ethnic labels. Significant numbers of adolescents changed
      their ethnic labels from year to year, however and these changes were associated
      with fluctuations in adolescents' ethnic affirmation and exploration and
      proficiency in their heritage languages.

PMID- 18717901
TI  - A developmental perspective on full- versus part-day kindergarten and children's
      academic trajectories through fifth grade.
AB  - Children's kindergarten experiences are increasingly taking place in full- versus
      part-day programs, yet important questions remain about whether there are
      significant and meaningful benefits to full-day kindergarten. Using the Early
      Childhood Longitudinal Study's Kindergarten Cohort (N= 13,776), this study takes
      a developmental approach to examining associations between kindergarten program
      type and academic trajectories from kindergarten (ages 4-6 years) through 5th
      grade (ages 9-12 years). Full-day kindergarten was associated with greater growth
      of reading and math skills from fall until spring of kindergarten. Initial
      academic benefits diminished soon after kindergarten. The fade-out of the full
      day advantage is in part explained by differences in the children who attend part
      and full-day kindergarten as well as school characteristics.

PMID- 18717902
TI  - Novel noun and verb learning in Chinese-, English-, and Japanese-speaking
      children.
AB  - When can children speaking Japanese, English, or Chinese map and extend novel
      nouns and verbs? Across 6 studies, 3- and 5-year-old children in all 3 languages
      map and extend novel nouns more readily than novel verbs. This finding prevails
      even in languages like Chinese and Japanese that are assumed to be verb-friendly
      languages (e.g., T. Tardif, 1996). The results also suggest that the input
      language uniquely shapes verb learning such that English-speaking children
      require grammatical support to learn verbs, whereas Chinese children require
      pragmatic as well as grammatical support. This research bears on how universally
      shared cognitive factors and language-specific linguistic factors interact in
      lexical development.

PMID- 18717903
TI  - Does chronic classroom peer rejection predict the development of children's
      classroom participation during the grade school years?
AB  - A sample of 398 children was followed up from ages 5 to 12 to investigate the
      relation between peer group rejection and classroom participation. The
      participation trajectories of individuals and groups of children who were
      rejected for differing periods of time were examined both during and after
      rejection using piecewise growth curve analyses. The results showed that whereas
      during periods of rejection, children exhibited negative or negligible growth in
      participation, when nonrejected, they manifested positive growth. These findings
      corroborated the hypothesis that (a) peer rejection creates constraints that
      inhibit children's classroom participation and (b) the cessation of rejection
      enables children to become more active and cooperative participants in classroom
      activities.

PMID- 18717904
TI  - Numerical magnitude representations influence arithmetic learning.
AB  - This study examined whether the quality of first graders' (mean age = 7.2 years)
      numerical magnitude representations is correlated with, predictive of, and
      causally related to their arithmetic learning. The children's pretest numerical
      magnitude representations were found to be correlated with their pretest
      arithmetic knowledge and to be predictive of their learning of answers to
      unfamiliar arithmetic problems. The relation to learning of unfamiliar problems
      remained after controlling for prior arithmetic knowledge, short-term memory for
      numbers, and math achievement test scores. Moreover, presenting randomly chosen
      children with accurate visual representations of the magnitudes of addends and
      sums improved their learning of the answers to the problems. Thus,
      representations of numerical magnitude are both correlationally and causally
      related to arithmetic learning.

PMID- 18717905
TI  - Investigating the development of data evaluation: the role of data
      characteristics.
AB  - A crucial skill in scientific and everyday reasoning is the ability to interpret
      data. The present study examined how data features influence data interpretation.
      In Experiment 1, one hundred and thirty-three 9-year-olds, 12-year-olds, and
      college students (mean age = 20 years) were shown a series of data sets that
      varied in the number of observations and the amount of variance between and
      within observations. Only limited context for the data was provided. In
      Experiment 2, similar data sets were presented to 101 participants from the same
      age groups incrementally rather than simultaneously. The results demonstrated
      that data characteristics affect how children interpret observations, with
      significant age-related increases in detecting multiple data characteristics, in
      using them in combination, and in explicit verbal descriptions of data
      interpretations.

PMID- 18717906
TI  - Intergenerational transmission of social anxiety: the role of social referencing
      processes in infancy.
AB  - Responses to an unfamiliar adult were examined in infants of mothers with social
      phobia (N= 79) and infants of nonanxious comparison mothers (N= 77) at 10 and 14
      months in a social referencing paradigm. On each occasion, a female stranger
      first interacted with the mother and then approached and interacted with the
      infant. Over time, infants of mothers with social phobia showed increasing
      avoidance of the stranger, particularly when they were behaviorally inhibited. In
      boys, maternal social phobia was associated with increasing fearful responses.
      Infant avoidance was predicted by expressed maternal anxiety and low levels of
      encouragement to interact with the stranger. The findings are discussed in
      relation to theories concerning the intergenerational transmission of social
      anxiety.

PMID- 18717907
TI  - Family resources and parenting quality: links to children's cognitive development
      across the first 3 years.
AB  - Reciprocal associations among measures of family resources, parenting quality,
      and child cognitive performance were investigated in an ethnically diverse, low
      income sample of 2,089 children and families. Family resources and parenting
      quality uniquely contributed to children's cognitive performance at 14, 24, and
      36 months, and parenting quality mediated the effects of family resources on
      children's performance at all ages. Parenting quality continued to relate to
      children's cognitive performance at 24 and 36 months after controlling for
      earlier measures of parenting quality, family resources, and child performance.
      Similarly, children's early cognitive performance related to later parenting
      quality above other measures in the model. Findings merge economic and
      developmental theories by highlighting reciprocal influences among children's
      performance, parenting, and family resources over time.

PMID- 18717908
TI  - Phonological and semantic priming in children with reading disability.
AB  - Lexical priming was assessed in children with reading disability (RD) and in age
      matched controls (M= 11.5 years), in visual and auditory lexical decision tasks.
      In the visual task, children with RD were found to have deficits in semantic
      (SHIP-BOAT), phonological/graphemic (GOAT-BOAT), and combined (FLOAT-BOAT)
      priming. The same pattern of semantic priming deficits also occurred in auditory
      lexical decisions, suggesting that the semantic deficits are not confined to
      reading. Children with RD also showed less priming than reading-age matched
      controls, suggesting that their priming deficits are not simply due to lower
      reading level but are due to the reading disability in particular. These semantic
      deficits may contribute to both the word reading and the comprehension problems
      seen in children with RD.

PMID- 18717909
TI  - Individual differences in adolescents' beliefs about the legitimacy of parental
      authority and their own obligation to obey: a longitudinal investigation.
AB  - Adolescents' beliefs about the legitimacy of parental authority and obligation to
      obey were examined in 568 Chilean adolescents (11-14 years old at Wave 1),
      followed once a year for 4 years. Adolescents' beliefs about parental legitimacy
      and obligation to obey declined with age. The steepest decline occurred during
      early adolescence, particularly in the personal domain. Adolescents who were
      uninvolved in problem behavior and perceived their parents to be supportive or
      high in monitoring at Wave 1 were more likely to endorse parental legitimacy and
      obligation to obey over time. There was little evidence that parenting or problem
      behavior moderated the normative decline in adolescents' beliefs about parental
      authority. Findings concerning individual differences in adolescents' endorsement
      of parental authority are highlighted in this study.

PMID- 18717910
TI  - The breadth of peer relationships among preschoolers: an application of the Q
      connectivity method to externalizing behavior.
AB  - Preschoolers' (M(age) = 48.7 months) social breadth (the number of peer children
      interact with and the frequency of these interactions) and the relations between
      breadth and externalizing behaviors were examined using the Q-connectivity
      method. After considering age, sex, and classroom effects on social breadth,
      children's externalizing behaviors were studied in relation to levels of social
      breadth across variations in frequency of exposure to peers and to patterns of
      decline in social breadth. Externalizing preschoolers occasionally interacted
      with most of their classmates. However, their individual peer networks moderately
      to rapidly became selective, and they engaged in repeated interactions with a
      relatively small number of peers. Although there were no sex effects, significant
      age and classroom effects were obtained.

PMID- 18717911
TI  - The effects of background television on the toy play behavior of very young
      children.
AB  - This experiment tests the hypothesis that background, adult television is a
      disruptive influence on very young children's behavior. Fifty 12-, 24-, and 36
      month-olds played with a variety of toys for 1 hr. For half of the hour, a game
      show played in the background on a monaural TV set. During the other half hour,
      the TV was off. The children looked at the TV for only a few seconds at a time
      and less than once per minute. Nevertheless, background TV significantly reduced
      toy play episode length as well as focused attention during play. Thus,
      background television disrupts very young children's play behavior even when they
      pay little overt attention to it. These findings have implications for subsequent
      cognitive development.

PMID- 18717912
TI  - German children's comprehension of word order and case marking in causative
      sentences.
AB  - Two comprehension experiments were conducted to investigate whether German
      children are able to use the grammatical cues of word order and word endings
      (case markers) to identify agents and patients in a causative sentence and
      whether they weigh these two cues differently across development. Two-year-olds
      correctly understood only sentences with both cues supporting each other--the
      prototypical form. Five-year-olds were able to use word order by itself but not
      case markers. Only 7-year-olds behaved like adults by relying on case markers
      over word order when the two cues conflicted. These findings suggest that
      prototypical instances of linguistic constructions with redundant grammatical
      marking play a special role in early acquisition, and only later do children
      isolate and weigh individual grammatical cues appropriately.

PMID- 18717913
TI  - The dynamics of life stressors and depressive symptoms in early adolescence: a
      test of six theoretical models.
AB  - Structural equation modeling was used to compare 6 competing theoretically based
      psychosocial models of the longitudinal association between life stressors and
      depressive symptoms in a sample of early adolescents (N= 907; 40% Hispanic, 32%
      Black, and 19% White; mean age at Time 1 = 11.4 years). Only two models fit the
      data, both of which included paths modeling the effect of depressive symptoms on
      stressors recall: The mood-congruent cognitive bias model included only
      depressive symptoms to life stressors paths (DS-->S), whereas the fully
      transactional model included paths representing both the DS-->S and stressors to
      depressive symptoms (S-->DS) effects. Social causation models and the stress
      generation model did not fit the data. Findings demonstrate the importance of
      accounting for mood-congruent cognitive bias in stressors-depressive symptoms
      investigations.

PMID- 18717914
TI  - Chronic disease: when in doubt, consider accrual into a randomized controlled
      trial (RCT).

PMID- 18717915
TI  - ABCB1 polymorphisms may have a minor effect on ciclosporin blood concentrations
      in myasthenia gravis patients.
AB  - AIMS: Ciclosporin (CsA), which is widely used in autoimmune disease and
      transplantation, has a narrow therapeutic index. It also shows considerable
      interindividual variability in its pharmacokinetics, which may be attributable to
      polymorphisms of the multidrug efflux pump P-glycoprotein, encoded by MDR-1. The
      aim was to determine the role of genetic polymorphisms in MDR-1 with respect to
      interindividual variability of CsA blood concentrations in myasthenia gravis (MG)
      patients. METHODS: MG patients (n = 129) receiving CsA were genotyped for MDR-1
      1236C-->T (exon 12), 2677G-->T (exon 21) and 3435C-->T (exon 26). Trough blood
      and peak blood concentrations were determined to see if there was correlation
      with the corresponding genotype. RESULTS: We observed a trend for CsA blood
      concentrations, especially peak blood concentrations, to be higher with the wild
      type allele compared with minor alleles in genotype and haplotype. Furthermore,
      under the same CsA regimen, it was found that the trough concentrations of
      variant genotype (ABCB1 1236TT or ABCB1 2677TT) were significant greater than
      those of wild-type (ABCB1 1236CC or ABCB1 2677GG, respectively) (P = 0.0222 and
      0.0081). The trough concentrations of wild-type haplotype pair group were
      significantly lower those that of the mutant type pair group (TT-TT-TT) (P =
      0.007). CONCLUSIONS: ABCB1 polymorphisms in both genotype and haplotype may have
      a minor effect on the CsA blood concentrations.

PMID- 18717916
TI  - Patients' understanding of the reasons for starting and discontinuing inhaled
      corticosteroids.
AB  - AIM: Although early discontinuation of treatment in new users of inhaled
      corticosteroids (ICS) has been widely discussed, the reasons for stopping have
      not been investigated in depth. We aimed to describe reasons for discontinuation
      from a patient's perspective in relation to their experience of symptoms at the
      time of the investigation. METHODS: A cross-sectional study among new users that
      discontinued ICS use in the Netherlands was performed. Patients were interviewed
      by telephone, aiming to identify the symptoms for which they were prescribed ICS,
      the reasons for discontinuing treatment and the respiratory symptoms patients
      still experienced at the time of the survey. In addition, automated dispensing
      records of all patients were retrieved. RESULTS: From 287 eligible patients, 230
      (80.1%) were interviewed. Only 22 patients (9.6%) mentioned asthma as the reason
      for a first ICS prescription. A decrease in symptoms was the main reason for
      discontinuation (45%). Thirty patients (13%) reported clinically significant
      residual symptoms. These patients reported more seasonal variation of symptoms
      and were more often prescribed short-acting beta(2)-agonists. CONCLUSIONS: The
      majority of patients mentioned a wide range of symptoms and conditions, other
      than asthma or chronic obstructive pulmonary disease, as the reason for the start
      of ICS therapy. Most of these conditions may be expected to be of short duration.
      Not surprisingly a decrease in symptoms was the main, and justifiable, reason for
      discontinuing ICS. However, a non-negligible proportion of patients reported
      residual symptoms that suggest the need of continued ICS use. Physicians and
      pharmacists could cooperate in identifying those patients for which ICS are
      really indicated and motivate them to continue the use of ICS.

PMID- 18717919
TI  - Integrative module-based family therapy: application and training.
AB  - The field of marriage and family therapy is currently at a crossroads. The
      challenge for contemporary therapists is how to incorporate the wisdom of
      previous models with the accountability that comes from evidence-based practice.
      The Integrative Module-Based Family Therapy treatment model provides a formalized
      series of steps that clinicians can use in their case planning and
      implementation. It is based on nine clinically relevant modules for assessment
      and intervention that are consistent with current best practices and empirically
      supported treatments. It thus meets the need for a structured family therapy
      practice and training approach that is respectful of the "art" of family therapy
      while still adhering to the principles of the "science" of evidence-based
      treatment.

PMID- 18717920
TI  - Multi-couple reflecting team: preliminary report.
AB  - The aim of therapeutic help in marital crisis is to break the vicious circle of
      mutual hurtful accusations. The method that the authors present below involves a
      group of couples working within a closed cycle of meetings. In the course of
      successive group meetings, the various couples act as reflecting teams (RTs) for
      each other. This achieves two objectives: the couple recounting their crisis
      receives nonthreatening feedback, which helps them to implement positive changes
      and break out of the self-perpetuating destructive interaction. In addition, the
      couples acting as the RT learn nonjudgmental, nontheorizing and affirmative
      communication.

PMID- 18717921
TI  - Emotionally Focused Therapy for couples and childhood sexual abuse survivors.
AB  - This study explored Emotionally Focused Therapy (EFT) for couples with childhood
      sexual abuse survivors (CSA) and their partners. Half of the couples in this
      study reported clinically significant increases in mean relationship satisfaction
      and clinically significant decreases in trauma symptoms, and thematic analyses
      identified numerous areas where trauma survivors were challenged in fully
      engaging in the therapy process. In particular, trauma symptoms such as affect
      dysregulation and hypervigilance were identified to play a role in the challenges
      that survivors experienced in fully engaging in the EFT process. Results of these
      thematic analyses yielded clinical recommendations for working with CSA survivors
      and their partners in EFT for traumatized couples. Recommendations for future
      study were articulated.

PMID- 18717922
TI  - Adolescent and parent alliances with therapists in Brief Strategic Family Therapy
      with drug-using Hispanic adolescents.
AB  - This study examined the relationship between alliance and retention in family
      therapy. Alliance was examined at the individual (parent, adolescent) and family
      level (within-family differences) for families that either dropped out or
      completed family therapy. Participants were 31 Hispanic adolescents and their
      family members who received brief strategic family therapy for the treatment of
      adolescent drug use. Videotapes of first sessions were rated to identify parent
      and adolescent alliances with the therapist. Results demonstrated that Completer
      cases had significantly higher levels of alliance across all family members than
      Dropout cases, and Dropout cases had significantly higher unbalanced alliances
      than Completer cases. Clinical implications are discussed.

PMID- 18717923
TI  - Common pitfalls of beginning therapists utilizing enactments.
AB  - Empirical data, clinical observation, and theoretical rationales support use of
      enactments as a fundamental mechanism of change in relationship therapies. Yet
      beginning therapists may lack an adequate conceptual framework and operational
      training essential to effectively utilize enactments. Inadequate training may
      contribute to ineffective execution, and in turn to negative results, which could
      lead to abandonment of enactments. This study sought to identify proficiencies
      and nonproficiencies of beginning therapists in conducting enactments. Twenty
      beginning therapists from three Commission on Accreditation for Marriage and
      Family Therapy Education (COAMFTE)-accredited programs were briefly trained in an
      indirect therapy style that incorporates enactments. Twenty-six therapist
      enactments were coded using a comprehensive observational measure designed to
      assess proficiencies and nonproficiencies in executing enactment phases,
      component tasks, and subcomponent operations. Results suggest that beginning
      therapists struggle with numerous clinical operations conceptually linked to the
      successful engagement of relationships in marriage and family therapy. In light
      of these findings, specific recommendations for additional enactment training in
      COAMFTE-accredited programs are offered.

PMID- 18717924
TI  - Examining the impact of gender, race/ethnicity, and family factors on mental
      health issues in a sample of court-involved youth.
AB  - Faced with anywhere between one half and two thirds of its youth having a
      diagnosable mental illness, the identification and treatment of mental health
      concerns is a critically important endeavor for professionals working with youth
      who have contact with the juvenile justice system. In addition, the literature
      suggests that factors related to both the family and to the gender of the
      adolescent must be incorporated into any approach to assessment and intervention
      within this special population. Further, prior work that has documented the
      interaction of gender and family issues with adolescent race/ethnicity warrants
      further empirical attention, as does the intermediary role that the family may
      play in the development of both internalizing and externalizing behaviors. The
      present study extends this literature by examining factors related to gender,
      race/ethnicity, family factors, and mental health issues in a sample of 2,549
      Caucasian and African American youth coming to the attention of juvenile courts.
      Multivariate analysis of variance results indicated significant main effects for
      gender and race/ethnicity, as well as a significant gender x race/ethnicity
      interaction for the family and externalizing variables. A multiple group
      structural equation modeling procedure was employed in order to test the
      hypothesis that family environment mediates the relationship between gender and
      mental health problems, as well as to test for potential differences in these
      relationships as a function of race/ethnicity. Results indicated support for the
      mediation model in the sample of African American youth but not in the sample of
      Caucasian youth.

PMID- 18717925
TI  - "Changing for my kid": fatherhood experiences of Mexican-origin teen fathers
      involved in the justice system.
AB  - A descriptive phenomenological study was conducted with six adolescent fathers of
      Mexican origin on juvenile probation for a variety of serious offenses. All
      participants successfully completed a parenting program designed especially for
      teen fathers. In a series of consecutive in-depth interviews, teen fathers were
      asked to discuss their experiences as fathers. Four phenomena were identified
      from the data: (a) not giving up and deciding to be a dad, (b) figuring out my
      relationships after becoming a father, (c) wanting to be a good father, and (d)
      wanting to be Brown and a father. Findings challenge negative stereotypes
      associated with Mexican-origin teen fathers engaged in delinquent behaviors and
      describe the ways in which fatherhood became an important positive motivator in
      the lives of participants.

PMID- 18717926
TI  - Conversational evidence in therapeutic dialogue.
AB  - Family therapists' participation in therapeutic dialogue with clients is
      typically informed by evidence of how such dialogue is developing. In this
      article, we propose that conversational evidence, the kind that can be
      empirically analyzed using discourse analyses, be considered a contribution to
      widening psychotherapy's evidence base. After some preliminaries about what we
      mean by conversational evidence, we provide a genealogy of evaluative practice in
      psychotherapy, and examine qualitative evaluation methods for their theoretical
      compatibilities with social constructionist approaches to family therapy. We then
      move on to examine the notion of accomplishment in therapeutic dialogue given how
      such accomplishments can be evaluated using conversation analysis. We conclude by
      considering a number of research and pedagogical implications we associate with
      conversational evidence.

PMID- 18717927
TI  - Positioning in the therapist's inner conversation: a dialogical model based on a
      grounded theory analysis of therapist reflections.
AB  - In recent years, a dialogical perspective has emerged in the family therapy field
      in which the therapist's inner conversation is conceptualized as a dialogical
      self. In this study, we analyze the data of a grounded theory study of therapist
      reflections and we portray the therapist's self as a dynamic multiplicity of
      inner positions embodied as voices, having dialogical relationships in terms of
      questions and answers or agreement and disagreement. We propose a descriptive
      model of the therapist's inner conversation with four positions. In this model,
      each of the four positions represents a concern of the therapist: attending to
      the client's process, processing the client's story, focusing on the therapist's
      own experience, and managing the therapeutic process. Detailed analyses of
      vignettes of therapist reflections illustrate the model, and implications of this
      model for training and supervision are considered.

PMID- 18717932
TI  - Abstracts of Stroke 2008 Conference-Combined Event of the Stroke Society of
      Australasia 2008 Annual Scientific Meeting & Smart Strokes - 4th Australasian
      Nursing and Allied Health Stroke Conference. 13-15 August, 13-15, 2008. Sydney,
      Australia.

PMID- 18717957
TI  - Sunscreens containing the broad-spectrum UVA absorber, Mexoryl SX, prevent the
      cutaneous detrimental effects of UV exposure: a review of clinical study results.
AB  - BACKGROUND: UVA exposure of human skin mainly produces reactive oxygen species
      (ROS) leading to DNA, cell and tissue damage. It alters immune function,
      pigmentation and it is certainly responsible for a large part of photoaging
      changes. Moreover UVA is implicated in the etiology of several photodermatoses.
      As a consequence, to provide adequate protection, sunscreens or skin care
      products for daily use protective products need UVA absorbers combined with UVB
      ones. AIM: To assess the efficacy of sunscreens containing a broad-spectrum UVA
      absorber the Mexoryls SX or ecamsule and to compare formulations with and without
      it through a large number of clinical studies in human volunteers and patients.
      METHODS: The following assessments were conducted: *Prevention of excessive
      pigmentation induced by UV exposure in Caucasian and Asian skins using a method
      that measures pigmentation protection factors (PPF). *Efficacy against DNA damage
      by measurement of pyrimidine dimer formation and p53 protein accumulation.
      *Protection of immune system using delayed type hypersensitivity (DTH) reactions
      to recall antigens, isomerization of urocanic acid (UCA), alteration of
      Langerhans cells (LC) density, morphology and function. *Reduction of epidermal
      and dermal alterations induced by repeated UVA or UV solar simulated radiation
      (SSR) using histology or immunohistology. *Prevention of the polymorphous light
      eruption (PMLE) in patients prone to develop this disease. RESULTS: Mexoryls SX
      containing formulations showed a dose-dependent level of protection against
      pigmentation. For a same sun protection factor (SPF) the higher the UVA
      protection was, the higher was the PPF. Pyrimidine dimer formation and p53
      accumulation were significantly reduced by formulations with Mexoryls SX. In the
      studies looking at the suppression of DTH reactions to recall antigens by the
      different UV spectra, the LC alterations and the cis UCA formation, Mexoryls SX
      formulations always showed a higher protective potency than sunscreen without it
      even when the protection against erythema was similar (products with same SPF).
      Mexoryls SX formulations also prevented or significantly decreased to minimal,
      ferritin, tenascin and lysozyme expression induced by repeated UVA or SSR
      exposure. It also reduced the enhancement of collagenase 2 mRNA expression
      induced by SSR exposure. Finally PMLE study demonstrated that UVA protection was
      essential for the prevention of this photodermatose. CONCLUSION: Mexoryls SX
      formulated in sunscreens or daily use products have been shown to be an effective
      UV absorber, leading to an increased efficacy of these products against a large
      number of biological damage induced by UVA, SSR or sun exposure.

PMID- 18717958
TI  - Protective effect of the Baicalin against DNA damage induced by ultraviolet B
      irradiation to mouse epidermis.
AB  - PURPOSE: To investigate whether topical application of Baicalin affords
      protecting Balb/C mice epidermis from ultraviolet (UV)B-induced DNA damage and
      its underlying mechanisms. METHODS: A DNA damage model of UVB irradiation-induced
      mice epidermis was established. The immunohistochemical staining, Southwestern
      dot-blotting were used for cyclobutane pyrimidine dimers (CPDs) detection;
      Western blotting was used for p53 detection; reverse transcription-polymerase
      chain reaction (RT-PCR) was used to detect the mRNA level of Bcl-2 and Bax;
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was
      used to detect apoptotic cells. RESULTS: Topical application of Baicalin on
      Balb/C mice skin significantly decreased the amount of epidermal CPDs 1, 24 and
      48 h after 180 mJ/cm(2) of UVB irradiation as compared with untreated mice. UVB
      induced apoptosis was less pronounced in Baicalin-treated mice epidermis, which
      was accompanied by less p53 accumulation and higher Bcl-2/Bax ratio compared with
      that of untreated mice. CONCLUSION: Taken together, these results suggest that
      topical Baicalin application mitigates DNA photo-damage. Baicalin is therefore a
      promising protective substance against UVB radiation.

PMID- 18717959
TI  - Aminolaevulinic acid diffusion characteristics in 'in vitro' normal human skin
      and actinic keratosis: implications for topical photodynamic therapy.
AB  - BACKGROUND: The response rate of aminolaevulinic acid (ALA)-based photodynamic
      therapy (PDT) in certain subtypes of actinic keratosis (AK), such as hypertrophic
      and hyperkeratotic lesions, is variable, an effect attributable to a supposed
      lack of ALA penetration. A detailed and depth-related profile of spatial ALA
      permeation in AK following drug administration would lead to a greater
      understanding of concentrations achievable before protoporphyrin IX biosynthesis
      and subsequent PDT. METHODS: ALA penetration through excised normal human skin
      (NS) and AK lesions was evaluated using a cryostatic sectioning technique and
      radio-isotope counting following drug delivery using a novel, bioadhesive patch,
      loaded with 19, 38 or 50 mg/cm(2) ALA. RESULTS: Distinct differences in ALA
      concentration with respect to depth between AK and NS samples were shown,
      particularly within the superficial layers of the tissue structure, down to a
      depth of 1.0 mm. Patch application times were shown to influence ALA
      concentrations in tissue, but there was no clear correlation between ALA
      penetration in AK lesions taken from different body locations and from patients
      of different age. Similarly, the thickness of stratum corneum was not related to
      the ALA distribution profiles. CONCLUSIONS: Sizable variation in ALA
      concentration was a prominent feature of profiles through AK lesions, which may
      explain the variation of observed protoporphyrin IX production seen in the
      clinical implementation of AK PDT. That said, the results of this study show
      sufficient ALA penetration to a depth of 1.0 mm, which should be satisfactory for
      successful treatment of the majority of non-hyperkeratotic, hypertrophic AK using
      patch-based delivery methods.

PMID- 18717960
TI  - Consistency of reported tanning behaviors and sunburn history among sorority and
      fraternity students.
AB  - BACKGROUND: Reliable measurements of behavior are crucial to evaluating health
      promotion efforts. The goal of this reliability study was to examine the
      consistency of recalled tanning behaviors in a population with a potentially high
      use. METHODS: We used the test-retest reliability of a self-administered survey
      to examine the consistency of reporting behavior patterns regarding artificial
      ultraviolet (UV) tanning, sunburns and sun sensitivity among sorority- and
      fraternity-affiliated university students. RESULTS: High reliability on test
      retest for questions evaluating the number of artificial UV tanning sessions and
      the number of sunburns during specific time periods was found. CONCLUSIONS:
      Overall, this study suggests that this sub-population of 18-23-year-olds, with a
      wider range of exposures than other 18-23-year-olds and older subjects, report
      lifetime artificial UV tanning consistently when required to recall time period
      specific exposures before estimating their lifetime exposure.

PMID- 18717961
TI  - Efficacy of three different laser wavelengths for in vitro wound healing.
AB  - BACKGROUND AND OBJECTIVE: Despite contradictory reports on the effect of laser
      light on cell proliferation, studies have shown that appropriate doses and
      wavelengths of laser light are therapeutically beneficial in tissue repair and
      pain control. This study aimed to establish if the dose and/or wavelength
      influenced the biological responses of irradiated in vitro fibroblasts--1 h after
      laser irradiation. MATERIALS AND METHODS: This study aimed to establish cellular
      responses of normal and wounded human skin fibroblasts to helium-neon (632.8 nm),
      diode (830 nm) and Nd:YAG (1064 nm) laser irradiation using one exposure of 5 or
      16 J/cm(2) on day 1 and again on day 4. RESULTS: Wounded cells exposed to 5
      J/cm(2) using 632.8 nm showed an increase in cell migration and haptotaxis, a
      stable increase in the release of interleukin-6 (IL-6), a decrease in caspase 3/7
      activity, an increase in ATP viability and an increase in cell proliferation--1 h
      after the final exposure. The results confirm that changes in parameters such as
      ATP viability, cytokine expression (IL-6), cell proliferation (alkaline
      phosphatase enzyme activity) and DNA damage can be observed directly after the
      laser irradiation. The amount of DNA damage and cytotoxicity may be related to
      duration of the laser irradiation, which is dependent on the power density
      (mW/cm(2)) of each laser. CONCLUSION: The results indicate that 5 J/cm(2) using
      632.8 nm results in a stimulatory effect that is more effective than 830 and 1064
      nm. The results suggest possible mechanisms by which the wavelength may
      potentially influence the cellular responses of wounded cells.

PMID- 18717962
TI  - Rates of allergic sensitization and irritation to oxybenzone-containing sunscreen
      products: a quantitative meta-analysis of 64 exaggerated use studies.
AB  - BACKGROUND/PURPOSE: Oxybenzone is an active ingredient found in sunscreen
      products that absorbs a broad spectrum of ultraviolet (UV) light, with absorbance
      peaking in the UVB region and extending into the UVA region. Although the overall
      incidence of sensitization and irritation associated with oxybenzone in the
      general population remains unclear, a few studies have reported on the incidence
      in specific circumstances. However, the relevance of these studies to the general
      population is limited, because the sample populations reported in these papers
      generally have consisted of individuals who sought medical attention for pre
      existing skin conditions. Therefore, the reported incidence of allergic reactions
      to oxybenzone in these studies may be overestimated as related to the general
      population. The objective of this meta-analysis was to determine the safety of
      oxybenzone in participants recruited from the general population. METHODS: The
      data from 64 unpublished exaggerated use human repeat insult patch tests (HRIPT)
      and photoallergy (PA) studies sponsored by Schering-Plough HealthCare Products
      Inc. between 1992 and 2006 were aggregated and analyzed to evaluate the irritancy
      and sensitization potential of sunscreen products containing oxybenzone at
      concentrations between 1% and 6%. RESULTS: Forty-eight of 19 570 possible dermal
      responses were considered to be suggestive of irritation or sensitization; the
      mean rate of responses across all formulations was 0.26%. Sensitization rates did
      not correlate significantly with oxybenzone concentration. The available re
      challenge data indicated that only eight of these responses were contact
      allergies from oxybenzone, and the mean rate of contact allergy to oxybenzone was
      0.07%. The source of the skin responses was not confirmed for 15 subjects who
      were lost to follow-up. However, all subjects were given the opportunity to
      participate in follow-up testing. CONCLUSION: Our data indicate that sunscreen
      products formulated with 1-6% oxybenzone do not possess a significant
      sensitization or irritation potential for the general public. Furthermore, these
      data suggest that the incidence rate implied in the published literature
      overestimates the actual incidence of sensitization/irritation due to oxybenzone
      containing sunscreen products in the general population.

PMID- 18717963
TI  - Commentary on 'UVB-SPF': the SPF labels of sunscreen products convey more than
      just UVB protection.
AB  - The FDA recently published a proposed amendment of the Final Monograph for OTC
      Sunscreen Products. Among the proposals, FDA revised solar simulator performance
      specifications and additional labeling for sunscreen products. The maximum
      allowable labeled sun protection factor (SPF) was increased to SPF 50 while
      simultaneously requiring it to be called 'UVB-SPF'. UVB accounts for 80-91% of
      the erythemic effectiveness of the UV solar simulator specified in the amendment.
      Analysis of the specified solar simulator spectrum used to determine SPF
      indicates that if 100% of the UVB is blocked, it is mathematically impossible to
      achieve an SPF in excess of approximately 11 without also blocking at least some
      UVA. Consequently significant UVA protection must be provided for sunscreen
      products to achieve SPFs of 15 and higher. At the maximum allowed SPF 50, where
      only 2% or less of the effective UV risk remains, the minimum reduction of UVA
      erythemal effectiveness must by definition be 78-90%. While mandating UVA
      protection criteria is doubtless important, especially as it relates to sunscreen
      photostability, there is no utility in, or basis for, the proposed 'UVB-SPF'
      descriptor as existing high SPF labeling indicates both UVB and UVA protection.

PMID- 18717964
TI  - Population and quantitative genetics for a cause.

PMID- 18717965
TI  - Molecular characterization, expression and association analysis of the porcine
      CMYA4 gene with carcass traits.
AB  - CMYA4 (cardiomyopathy-associated 4) gene plays an important role in thick
      filament assembly. In this study, we obtained the mRNA sequence including the
      full coding sequence and the partial 5' untranslated region of the porcine CMYA4
      gene by using the rapid amplification of cDNA ends and reverse transcriptase
      polymerase chain reaction (RT-PCR) and the sequence was deposited in the GenBank
      nucleotide database (DQ_286571). The human (NM_173167) and mouse (NM_178680)
      homologues have a 91% and 87% identity with the porcine CMYA4 gene, respectively.
      The sequence contains an open reading frame encoding 930 amino acid residues, and
      the amino terminus of the predicted CMYA4 protein contains three tandem repeats
      belonging to the tetratricopeptide repeat family. Semi-quantitative RT-PCR
      results showed that the porcine CMYA4 gene is expressed exclusively in striated
      muscle tissue. An A558G single nucleotide polymorphism in the CMYA4 intron 15
      detected as an MspI PCR-restriction fragment length polymorphism showed allele
      frequency differences among 225 unrelated pigs from six breeds. Association of
      the genotypes with growth and carcass traits showed that different genotypes of
      the CMYA4 gene were significantly associated with the backfat thickness of the
      area between sixth and seventh ribs (p < 0.05) and backfat thickness at the
      shoulder (p < 0.05).

PMID- 18717966
TI  - Investigation of QTL regions on Chromosome 17 for genes associated with meat
      color in the pig.
AB  - Previous studies have uncovered several significant quantitative trait loci (QTL)
      relevant to meat colour traits mapped at the end of SSC17 in the pig.
      Furthermore, results released from the porcine genome sequencing project have
      identified genes underlying the entire QTL regions and can further contribute to
      mining the region for likely causative genes. Ten protein coding genes or novel
      transcripts located within the QTL regions were screened for single nucleotide
      polymorphisms (SNPs). Linkage mapping and association studies were carried out in
      the ISU Berkshire x Yorkshire (B x Y) pig resource family. The total length of
      the new SSC17 linkage map was 126.6 cM and additional markers including
      endothelin 3 (EDN3) and phosphatase and actin regulator 3 (PHACTR3) genes were
      assigned at positions 119.4 cM and 122.9 cM, respectively. A new QTL peak was
      noted at approximately 120 cM, close to the EDN3 gene, and for some colour traits
      QTL exceeded the 5% chromosome-wise significance threshold. The association
      analyses in the B x Y family showed that the EDN3 BslI and PHACTR3 PstI
      polymorphisms were strongly associated with the subjective colour score and
      objective colour reflectance measures in the loin, as well as average drip loss
      percentage and pH value. The RNPC1 DpnII and CTCFL HpyCH4III polymorphisms were
      associated with some meat colour traits. No significant association between
      CBLN4, TFAP2C, and four novel transcripts and meat colour traits were detected.
      The association analyses conducted in one commercial pig line found that both
      EDN3 BslI and PHACTR3 PstI polymorphisms were associated with meat colour
      reflectance traits such as centre loin hue angle and Minolta Lightness score. The
      present findings suggested that the EDN3 and PHACTR3 genes might have potential
      effects on meat colour in pigs, and molecular mechanisms of their functions are
      worth exploring.

PMID- 18717967
TI  - Variation at the insulin-like growth factor 1 gene and its association with body
      weight traits in the chicken.
AB  - The insulin-like growth factor 1 (IGF1) is essential for normal embryonic and
      postnatal growth in mammals. In this study, a total of 342 F(2) individuals,
      derived from Broiler crossing to Baier layer (Northeast Agricultural University
      Resource Population, NEAURP), were used to investigate the associations of
      haplotypes in the chicken IGF1 (cIGF1) gene with body weight traits. Primers for
      the 5'-flanking, exon 3 and 3'-flanking regions of cIGF1 were designed according
      to chicken genome database. Single nucleotide polymorphisms (SNPs) between
      parental lines were detected by sequencing, and PCR restriction fragment length
      polymorphism (PCR-RFLP) and PCR single-stranded-conformation polymorphism (PCR
      SSCP) methods were used to genotype the SNPs in the population. Haplotypes were
      constructed with the three SNPs detected. The association analysis showed that
      haplotypes based on three cIGF1 polymorphisms (c.-366A>C, c.528G>A and
      c.*1024C>T) were associated with body weight traits, suggesting that cIGF1 or a
      tightly linked gene had effects on body weight in the chicken.

PMID- 18717968
TI  - Bovine SLC11A1 3' UTR SSCP genotype evaluated by a macrophage in vitro killing
      assay employing a Brucella abortus strain.
AB  - The 3' untranslated region (3' UTR) of the bovine natural resistance-associated
      macrophage gene (NRAMP1 or SLC11A1) was genotyped in Colombian Creole Blanco
      Orejinegro (BON) (Bos taurus) (n = 140) and Zebu Brahman (Bos indicus) (Z) (n =
      20) cattle and their crosses (BON x Zebu Brahman [B x Z] [n = 10]; Zebu Brahman x
      BON [Z x B] [n = 10]), and in animals from a Holstein x BON (H x B) (n = 10)
      cross. Direct sequencing and single-strand conformation polymorphism analysis
      (SSCP) helped in detecting the polymorphic behaviour. The association between
      resistance to brucellosis infection and SSCP genotype was evaluated using a
      macrophage in vitro killing assay employing a virulent Brucella abortus strain.
      The 3' UTR (GT) repeated polymorphism was gentoyped and its association with
      resistance to brucellosis was evaluated. When all breeds were grouped, a high
      frequency in the homozygote GT(12) (AA genotype) (0.823) and a very low frequency
      in the homozygote GT(10) (BB genotype) (0.047) were detected. The BON (0.963), Z
      x B (0.60) and H x B (1.00) cattle showed high GT(12) allele frequencies, unlike
      that seen for the B x Z and Zebu cattle (0.3002 and 0.218, respectively). The
      GT(10) allele was only found in the Zebu cattle (0.391). A significant
      association (p < 0.001) was found between the B. abortus macrophage in vitro
      killing assay phenotypes and the bovine SLC11A1 3' UTR genotypes, which suggests
      that the A allele may be associated with resistance. Because only nine animals
      had the BB genotype, the results require some confirmation in more extensive
      populations.

PMID- 18717969
TI  - Detection of quantitative trait loci affecting non-return rate in French dairy
      cattle.
AB  - The purpose of this study was to map quantitative trait loci (QTL) influencing
      female fertility estimated by non-return rate (NRR) in the French dairy cattle
      breeds Prim'Holstein, Normande and Montbeliarde. The first step was a QTL
      detection study on NRR at 281 days after artificial insemination on 78 half-sib
      families including 4993 progeny tested bulls. In Prim'Holstein, three QTL were
      identified on Bos taurus chromosomes BTA01, BTA02 and BTA03 (p < 0.01), whereas
      one QTL was identified in Normande on BTA01 (p < 0.05). The second step aimed at
      confirming these three QTL and refining their location by selecting and
      genotyping additional microsatellite markers on a sub-sample of 41 families from
      the three breeds using NRR within 56, 90 and 281 days after AI. Only the three
      QTL initially detected in Prim'Holstein were confirmed. Moreover, the analysis of
      NRR within 56, 90 and 281 days after AI allowed us to distinguish two FF QTL on
      BTA02 in Prim'Holstein, one for NRR56 and one for NRR90. Estimated QTL variance
      was 18%, 14%, 11.5% and 14% of the total genetic variance, respectively, for QTL
      mapping to BTA01, BTA02 (NRR90 and NRR56) and BTA03.

PMID- 18717971
TI  - Impact of the UKPDS--an overview.
AB  - The UK Prospective Diabetes Study (UKPDS) is a group of clinical trials,
      epidemiological analyses and health-modelling studies with an influence which can
      be assessed across a broad range of health domains. Original publications (n =
      85) are notable for being mainly published in the key weekly or diabetes journals
      (78%) and being mainly in the clinical arena (68%). Notable reference to the
      publications can be found in UK National Institute for Clinical Excellence (NICE)
      guidelines, but also in evidence-based international guidelines, where UKPDS
      papers form a significant fraction of the citations. In educational materials
      UKPDS-derived slides remain popular (10 and 30% of some international slide
      sets), again as much for the epidemiological findings as for the core trial
      results. Slides of the deterioration in blood glucose control with time, and
      evidence that this is as a result of progressive decline of pancreatic islet B
      cell function, are used particularly often. The UKPDS enhanced the promotion of
      glycated haemoglobin to its core role in clinical monitoring, through
      understanding of the quantitative relationship of vascular complications to
      glucose control, and thus to target setting. Notably, metformin therapy was
      promoted by the UKPDS findings on macrovascular disease in the overweight study,
      although controversy remains regarding the significance of the effect on
      macrovascular disease of the core glucose-lowering study, promoting the
      development of further studies reporting in 2008. The effects of decreasing blood
      pressure on microvascular disease have had an important impact on guidelines and
      health economic analyses, together with other evidence on the value of rennin
      angiotensin system blockers. The UKPDS has evidently been unusually influential
      in the development of treatment guidelines, clinical education and the thinking
      of healthcare professionals. By inference it must be responsible for a
      significant part of the improvement in health outcomes in people with Type 2
      diabetes over the last decade.

PMID- 18717972
TI  - Glucose control in the UKPDS: what did we learn?
AB  - The UK Prospective Diabetes Study (UKPDS) set out to establish whether improved
      glucose control could alleviate the macrovascular and microvascular complications
      of diabetes and to compare the relative merits of diet, oral glucose-lowering
      agents or insulin in achieving this objective. The study broke many of the rules
      of trial design, not least by constant addition of further interventions and
      analyses, but this flexibility would, paradoxically, prove to be one of its
      greatest strengths. The UKPDS taught us that glucose control must be tackled
      aggressively in Type 2 diabetes. It taught us that treatment must be escalated in
      parallel with the evolution of pancreatic B-cell failure. It also taught us that
      glucose control is not enough: the central objective of therapy is to reduce
      vascular risk by any means available. This commentary looks back along the
      winding road that led to these conclusions.

PMID- 18717973
TI  - The Hypertension in Diabetes Study (HDS): a catalyst for change.
AB  - Hypertension is now established as a major risk factor for premature
      cardiovascular morbidity and mortality in people with Type 2 diabetes and all
      modern treatment guidelines recommend the routine treatment of hypertension in
      these patients. However, these developments have been relatively recent. Only a
      decade ago, outside of small studies in patients with nephropathy, there was
      little evidence with regard to the efficacy and safety of treating elevated blood
      pressure in people with Type 2 diabetes. Consequently, for many patients,
      elevated blood pressure remained undetected and untreated. This changed with the
      publication of the Hypertension in Diabetes Study (HDS) in 1998. This study
      revealed that hypertension was very common in people with Type 2 diabetes and
      demonstrated the dramatic benefits of blood pressure lowering in reducing their
      risk of major macrovascular and microvascular complications. The unequivocal
      evidence from this study provided a much-needed catalyst for change, propelling
      blood pressure measurement and its treatment to the forefront of risk management
      in these patients. Many studies have followed and many questions remain with
      regard to the preferred anti-hypertensive treatment strategy and optimal
      treatment targets for blood pressure. In the meantime, many millions of patients
      with Type 2 diabetes worldwide have benefited and will continue to benefit from
      the therapeutic insights gained from the treatment of blood pressure in the 1148
      patients enrolled in the Hypertension in Diabetes Study in the UK Prospective
      Diabetes Study.

PMID- 18717974
TI  - Microvascular disease: what does the UKPDS tell us about diabetic retinopathy?
AB  - Background The UK Prospective Diabetes Study (UKPDS) was a randomised controlled
      clinical study which looked at the effect of improved blood glucose and blood
      pressure control on macro- and microvascular complications in Type 2 diabetes.
      Retinopathy was the commonest microvascular outcome and this paper looks at this
      complication. Methods Newly diagnosed diabetic patients were randomised to
      intensive or conventional glycaemic control and a subset of hypertensive patients
      to tight or less tight blood pressure control. Patients were seen every 3 months
      in study clinics and retinopathy was assessed by adjudicated grading of triennial
      colour retinal photographs. Photocoagulation treatment, vitreous haemorrhage and
      cataract extraction were predefined UKPDS endpoints. Observational analyses of
      the data were used to examine the relationship of updated mean glycated
      haemoglobin (HbA(1c)) and mean blood pressure levels to retinopathy outcomes.
      Results The UKPDS showed that both improved glucose control and improved blood
      pressure control reduced the risk of retinopathy, with a linear relationship
      between the log hazard ratio for retinopathy and both updated mean HbA(1c) and
      updated mean blood pressure. A 1% decrement in HbA(1c) equated to a 31% reduction
      in retinopathy and a 10 mmHg decrement in systolic blood pressure equated to an
      11% reduction in photocoagulation or vitreous haemorrhage. Evidence of
      retinopathy at diagnosis, including the presence of microaneurysms only,
      increased significantly the risk of progression to photocoagulation. Conclusions
      The UKPDS stands out as a landmark study in Type 2 diabetes, emphasising the
      crucial importance of controlling both blood glucose and blood pressure in order
      to minimise the risk of developing sight-threatening retinopathy.

PMID- 18717975
TI  - Microvascular disease: what does the UKPDS tell us about diabetic nephropathy?
AB  - The UK Prospective Diabetes Study is the largest study in Type 2 diabetes with
      pre-specified renal outcomes. The study showed that the natural history of
      nephropathy in newly diagnosed Type 2 diabetic patients was similar to that
      described previously in those with Type 1 diabetes. Around 2% per annum progress
      from normo- to micro-albuminuria [urinary albumin concentration (UAC) > 50 mg/l]
      and a further 2% from microalbuminuria to clinical grade proteinuria (UAC > 300
      mg/l). Mortality rates for those with nephropathy are high, increasing from 1.4%
      per annum (normoalbuminuria) to 4.6% per annum (clinical grade proteinuria), and
      to 19.2% per annum for those with renal impairment. More intensive blood glucose
      control resulted in both a 33% reduction in relative risk of development of
      microalbuminuria or clinical grade proteinuria at 12 years, and a significant
      reduction in the proportion doubling their plasma creatinine (0.91 vs. 3.52%, P =
      0.0028). Tighter blood pressure control also reduced microalbuminuria and
      clinical grade proteinuria; but at 6 years there was no effect on plasma
      creatinine levels. These data underline the importance of glycaemic and blood
      pressure control in Type 2 diabetes in order to prevent diabetic nephropathy.
      Those patients unlucky enough to develop nephropathy need intensive surveillance
      and correction of cardiovascular risk factors.

PMID- 18717976
TI  - Autoimmune diabetes in adults: lessons from the UKPDS.
AB  - Latent autoimmune diabetes in adults (LADA) is characterised by a relatively mild
      diabetes onset, autoantibody positivity and eventual requirement for insulin
      therapy. Twelve per cent of newly diagnosed, UK Prospective Diabetes Study
      (UKPDS) patients were positive for autoantibodies to GAD65 (GADA) and/or
      insulinoma-associated antigen-2A (IA-2A) and managed as if they had Type 2
      diabetes according to the UKPDS protocol. Here, we compare data from UKPDS LADA
      patients with that from other cohorts. In common with other groups, UKPDS LADA
      patients required insulin therapy earlier post-diagnosis than non-LADA patients.
      Reduction of islet function was similar in UKPDS LADA groups randomised to oral
      glucose-lowering agents or insulin replacement therapy, contesting the current
      hypothesis of reduced decline of insulin secretion in LADA by immediate insulin
      therapy. Disease progression was not predicted by post-diagnosis GADA levels or
      epitope specificities as has been suggested. Slowly progressing insulitis and
      pancreatic beta-cell loss at post-mortem are consistent with sustained retention
      of residual C-peptide secretion in LADA. Genetic association patterns at the
      human leucocyte antigen (HLA) and insulin gene (INS) regions are similar in UKPDS
      LADA patients and individuals with adult and childhood-onset Type 1 diabetes. The
      combined evidence suggests that LADA is an adult-onset form of Type 1 diabetes,
      rather than a separate condition or an intermediate state in a continuum of
      phenotype from Type 1 to Type 2 diabetes.

PMID- 18717977
TI  - Genetics: how the UKPDS contributed to determining the genetic landscape of Type
      2 diabetes.
AB  - The identification and functional characterisation of genetic variants that
      either cause or predispose to diabetes is a major focus of biomedical research.
      The molecular basis is now known for the majority of monogenic forms of diabetes
      arising from pancreatic beta-cell dysfunction; however finding the genetic
      variants underlying susceptibility to Type 2 diabetes (T2DM) has been a greater
      technical, statistical and biological challenge. The advent of biology-agnostic
      approaches made possible by the improved arsenal of research platforms and
      genetic tools available has increased the number of known T2DM genes dramatically
      and provided important insights into the pathophysiology of T2DM. Over the past
      18 months, the list of T2DM susceptibility genes has grown from three to close to
      20, illustrating the substantial progress which has been made. These recent
      milestones have not only illustrated the limited knowledge we have of the
      pancreatic beta-cell, but have also reinforced our belief in the involvement of
      common genetic variants in the genes involved in monogenic forms of diabetes in
      the susceptibility to T2DM and have clearly shown a primary role for pancreatic
      beta-cell dysfunction in T2DM. Both of these concepts were explored in the early
      work of the UK Prospective Diabetes Study (UKPDS) genetics research groups.

PMID- 18717978
TI  - UKPDS-modelling of cardiovascular risk assessment and lifetime simulation of
      outcomes.
AB  - Although known principally as a clinical trial, the UK Prospective Diabetes Study
      (UKPDS) provided longitudinal data which helped define the natural history of
      cardiovascular complications in Type 2 diabetes. Using clinical, epidemiological,
      statistical and economics methods, UKPDS investigators developed mathematical
      models that helped define predictors (risk factors) for cardiovascular disease
      including angina, myocardial infarction, stroke, peripheral vascular disease and
      death in Type 2 diabetes. The UKPDS made clearer the contributions to risk of
      age, hyperglycaemia, elevated blood pressure, adverse blood lipids and smoking.
      Equations were developed, combined and incorporated into the UKPDS Risk Engine
      and the UKPDS Outcomes models. For example, the UKPDS risk engine-version 2
      estimates that a white 62-year-old man with 11 years of Type 2 diabetes, a
      glycated haemoglobin of 8.3%, a systolic blood pressure of 145 mmHg and total and
      high-density lipoprotein cholesterol values of 5.8 and 1.1 mmol/l who did not
      smoke has a 33% chance of having overt coronary heart disease within 10 years.
      These models contribute to the estimation of risk and/or health outcomes adjusted
      for quality of life for use by, amongst others, clinicians, trialists, health
      planners, guideline developers and health economists.

PMID- 18717979
TI  - The economic analyses of the UK prospective diabetes study.
AB  - An economic analysis was not initially included in the study design of the UK
      Prospective Diabetes Study (UKPDS). However, data were collected throughout the
      study on hospital drugs and medications used and these were supplemented near the
      end of the study by cross-sectional surveys of non-inpatient healthcare use and
      quality of life. Evaluations of tight vs. less tight blood pressure control,
      intensive vs. less conventional blood glucose control and metformin showed that
      each was highly cost-effective and that all could be provided at modest total
      cost. Further analyses showed that amputations and stroke had particularly severe
      consequences for quality of life, and that amputations and non-fatal MI had high
      cost consequences. Finally, patient-level data were used to construct a diabetes
      outcomes model, which estimates the probability of longer-term complications from
      patient-specific risk factors and can be used in populations at different stages
      of diabetes progression. The economic analyses arising from the UKPDS have
      provided new evidence to clinicians, policymakers and researchers on the
      consequences of diabetes and the cost-effectiveness of interventions, thereby
      assisting the development of treatment guidelines and improved standards of care.
      The analyses also illustrated a number of methodological innovations. Finally,
      the UKPDS Outcomes Model is gaining widespread acceptance as a validated tool for
      long-term economic and clinical prediction in diabetes.

PMID- 18717980
TI  - Ethnic diversity in type 2 diabetes.
AB  - BACKGROUND AND METHODS: The present review assesses published data relating to
      the main ethnic groups in the UK Prospective Diabetes Study (UKPDS), namely White
      Caucasians (WC; 82% of the cohort), Indian-Asians (IA; 10%) and Afro-Caribbeans
      (AC; 8%). RESULTS: At entry, the IA patients were younger than WC and AC
      patients, had a greater waist-hip ratio and more sedentary lifestyle, but had the
      lowest prevalence of hypertension and current smoking. The AC patients had the
      poorest glycaemic control but the most favourable lipid profile. The differences
      in modifiable vascular risk factors did not change over 9 years of follow-up.
      Consistent with UKPDS exclusion criteria, few patients had complications at
      baseline and there were no between-group differences. An interim analysis of
      incident fatal/non-fatal myocardial infarction (median follow-up 8.7 years)
      showed that the AC patients had a 70% lower risk than WC after adjustment for
      explanatory variables and that IA patients had a similar risk to WC. An analysis
      of complete albuminuria and renal failure data (median follow-up 15 years) showed
      that IA ethnicity was independently associated with an increased risk.
      CONCLUSIONS: There are sustained ethnic differences in the nature of diabetes,
      including vascular risk factors. AC patients had a substantially reduced risk of
      myocardial infarction that was not explained by their more favourable lipid
      profile, while IA patients were more likely to develop nephropathy than WC and IA
      patients. Longer follow-up is needed to determine whether the increased
      macrovascular risk observed in IA patients in other studies is replicated in the
      UKPDS cohort.

PMID- 18717981
TI  - The UKPDS and its global impact.
AB  - Aim To review the world-wide impact of the United Kingdom Prospective Diabetes
      Study (UKPDS) on diabetes health care since publication of the main study results
      in 1998. Methods The major papers published by the UKPDS were reviewed, e-mails
      and faxes were sent to diabetes associations in various regions of the world
      seeking information on trends in HbA1c over the past decade and similar
      information was obtained from a major USA laboratory. Results The UKPDS extended
      to type 2 diabetes and brought to completion the case for linking the
      microvascular vascular complications of diabetes to control of blood glucose
      initially demonstrated by the Diabetes Control and Complications Trial (DCCT).
      This helped set the standard of care for diabetes to seek an HbA1c goal of at
      least < 7.0% with intensive glycemic treatment and formed a fundamental part of
      continuing medical education. This also helped stimulate new hypoglycemic drug
      development and the preferential use of metformin as first line therapy was
      supported by UKPDS results. In many areas of the world, including the United
      Kingdom and the USA, a national trend to lower HbA1c levels has been seen.
      Economic analyses have shown UKPDS intensive treatment to be cost-effective at
      6028 Ibs. per quality life year gained, imposing a reasonable burden on the
      British National health care budget. Conclusions The UKPDS was a landmark study
      in the treatment of type 2 diabetes from the time of diagnosis that has
      influenced standards of care and treatment guidelines throughout the world.

PMID- 18717982
TI  - Climate change, building energy use, and indoor environmental quality.

PMID- 18717983
TI  - Is a quantitative risk assessment of air quality in underground parking garages
      possible?
AB  - Little information is available about the health risks associated with time spent
      in underground parking garages. The objective of this study was to determine
      whether it is possible to quantify the health risks associated with these garages
      without epidemiologic data on the subject. We followed the standard procedure for
      health risk assessment. We searched the literature for pollutant concentrations
      in the air samples of underground parking garages, the hazards associated with
      their inhalation, and their toxicological reference values. Conditions of
      occupational and user exposure were estimated by scenarios and taken into account
      to discuss toxicological reference values by modifying (with Haber's law) the
      adjustment factors for exposure frequency and duration. Risk quantification was
      possible for 39 pollutants. Acute exposures to CO and NO2 exceed toxicological
      reference values, as does chronic exposure to benzene for threshold effects. The
      risk of a carcinogenic effect associated with benzene may be greater than 10(-5).
      Excess exposure to air pollution indicators (PM and NO2) is also elevated,
      judging by the WHO Air Quality Guidelines, and also when comparing to levels with
      reported effects in epidemiologic studies. The risk associated with underground
      parking garages can be evaluated only in part. The information available is
      nonetheless sufficient to justify actions to reduce exposure. PRACTICAL
      IMPLICATIONS: The risks associated with exposure in underground parking garages
      cannot be thoroughly evaluated because of inadequate knowledge of exposures and
      of the toxicity of pollutants. The available knowledge is nonetheless sufficient
      to advise that risk management measures should be taken to reduce both acute and
      chronic exposures.

PMID- 18717984
TI  - Evaluating building-related symptoms using the US EPA BASE study results.
AB  - In order to develop baseline data about United States office buildings, the
      United States Environmental Protection Agency conducted the Building Assessment
      Survey Evaluation (BASE) study, a systematic survey of 100 randomly selected
      United States office buildings, in the 1990s. This paper analyzes the self
      reported work-related symptoms and job and workplace characteristics of 4326
      respondents and compares results to the National Institute for Occupational
      Safety and Health's (NIOSH) study of 80 'complaint' buildings. Four distinct
      groups of symptoms, representing 'tiredness', 'mucosal irritation',
      'neuropsychological', and 'lower respiratory' conditions emerged from factor
      analysis of work-related symptoms. The symptom grouping is identical for both
      surveys. Although the prevalence of each symptom is significantly higher in the
      NIOSH than in the BASE sample, there is overlap of the symptom distributions. In
      the BASE survey, 45% of the work force reported at least one work-related health
      symptom; 20% reported at least three symptoms. These findings imply that it is
      counterproductive to dichotomize buildings into healthy vs. unhealthy; instead
      the prevalence of health problems related to buildings span a continuum.
      PRACTICAL IMPLICATIONS: These results indicate that most office buildings have
      occupants who report building-related symptoms. This paper provides practical
      guidance for the comparison of building prevalences to the BASE normative data.
      Work-related symptom distributions and symptom groups can improve investigators'
      ability to identify IEQ problems.

PMID- 18717985
TI  - Comparison of prognostic gene expression signatures for breast cancer.
AB  - BACKGROUND: During the last years, several groups have identified prognostic gene
      expression signatures with apparently similar performances. However, signatures
      were never compared on an independent population of untreated breast cancer
      patients, where risk assessment was computed using the original algorithms and
      microarray platforms. RESULTS: We compared three gene expression signatures, the
      70-gene, the 76-gene and the Gene expression Grade Index (GGI) signatures, in
      terms of predicting distant metastasis free survival (DMFS) for the individual
      patient. To this end, we used the previously published TRANSBIG independent
      validation series of node-negative untreated primary breast cancer patients. We
      observed agreement in prediction for 135 of 198 patients (68%) when considering
      the three signatures. When comparing the signatures two by two, the agreement in
      prediction was 71% for the 70- and 76-gene signatures, 76% for the 76-gene
      signature and the GGI, and 88% for the 70-gene signature and the GGI. The three
      signatures had similar capabilities of predicting DMFS and added significant
      prognostic information to that provided by the classical parameters. CONCLUSION:
      Despite the difference in development of these signatures and the limited overlap
      in gene identity, they showed similar prognostic performance, adding to the
      growing evidence that these prognostic signatures are of clinical relevance.

PMID- 18717986
TI  - GPCRTree: online hierarchical classification of GPCR function.
AB  - BACKGROUND: G protein-coupled receptors (GPCRs) play important physiological
      roles transducing extracellular signals into intracellular responses.
      Approximately 50% of all marketed drugs target a GPCR. There remains considerable
      interest in effectively predicting the function of a GPCR from its primary
      sequence. FINDINGS: Using techniques drawn from data mining and
      proteochemometrics, an alignment-free approach to GPCR classification has been
      devised. It uses a simple representation of a protein's physical properties.
      GPCRTree, a publicly-available internet server, implements an algorithm that
      classifies GPCRs at the class, sub-family and sub-subfamily level. CONCLUSION: A
      selective top-down classifier was developed which assigns sequences within a GPCR
      hierarchy. Compared to other publicly available GPCR prediction servers, GPCRTree
      is considerably more accurate at every level of classification. The server has
      been available online since March 2008 at URL: http://igrid
      ext.cryst.bbk.ac.uk/gpcrtree/.

PMID- 18717987
TI  - Same-strand overlapping genes in bacteria: compositional determinants of phase
      bias.
AB  - BACKGROUND: Same-strand overlapping genes may occur in frameshifts of one (phase
      1) or two nucleotides (phase 2). In previous studies of bacterial genomes, long
      phase-1 overlaps were found to be more numerous than long phase-2 overlaps. This
      bias was explained by either genomic location or an unspecified selection
      advantage. Models that focused on the ability of the two genes to evolve
      independently did not predict this phase bias. Here, we propose that a purely
      compositional model explains the phase bias in a more parsimonious manner. Same
      strand overlapping genes may arise through either a mutation at the termination
      codon of the upstream gene or a mutation at the initiation codon of the
      downstream gene. We hypothesized that given these two scenarios, the frequencies
      of initiation and termination codons in the two phases may determine the number
      for overlapping genes. RESULTS: We examined the frequencies of initiation- and
      termination-codons in the two phases, and found that termination codons do not
      significantly differ between the two phases, whereas initiation codons are more
      abundant in phase 1. We found that the primary factors explaining the phase
      inequality are the frequencies of amino acids whose codons may combine to form
      start codons in the two phases. We show that the frequencies of start codons in
      each of the two phases, and, hence, the potential for the creation of overlapping
      genes, are determined by a universal amino-acid frequency and species-specific
      codon usage, leading to a correlation between long phase-1 overlaps and genomic
      GC content. CONCLUSION: Our model explains the phase bias in same-strand
      overlapping genes by compositional factors without invoking selection. Therefore,
      it can be used as a null model of neutral evolution to test selection hypotheses
      concerning the evolution of overlapping genes.

PMID- 18717988
TI  - Marine metagenomics: strategies for the discovery of novel enzymes with
      biotechnological applications from marine environments.
AB  - Metagenomic based strategies have previously been successfully employed as
      powerful tools to isolate and identify enzymes with novel biocatalytic activities
      from the unculturable component of microbial communities from various terrestrial
      environmental niches. Both sequence based and function based screening approaches
      have been employed to identify genes encoding novel biocatalytic activities and
      metabolic pathways from metagenomic libraries. While much of the focus to date
      has centred on terrestrial based microbial ecosystems, it is clear that the
      marine environment has enormous microbial biodiversity that remains largely
      unstudied. Marine microbes are both extremely abundant and diverse; the
      environments they occupy likewise consist of very diverse niches. As culture
      dependent methods have thus far resulted in the isolation of only a tiny
      percentage of the marine microbiota the application of metagenomic strategies
      holds great potential to study and exploit the enormous microbial biodiversity
      which is present within these marine environments.

PMID- 18717989
TI  - Rabies trend in China (1990-2007) and post-exposure prophylaxis in the Guangdong
      province.
AB  - BACKGROUND: Rabies is a major public-health problem in developing countries such
      as China. Although the recent re-emergence of human rabies in China was noted in
      several epidemiological studies, little attention was paid to the reasons behind
      this phenomenon paralleling the findings of the previous reports. The purpose of
      this study is thus first to characterize the current trends of human rabies in
      China from 1990 to 2007, and then to define better recommendations for improving
      the post-exposure prophylaxis (PEP) schedules delivered to rabies patients.
      METHODS: The most updated epidemiological data for 22527 human rabies cases from
      January 1990 to July 2007, retrieved from the surveillance database of reportable
      diseases managed by the Ministry of Health of China, were analysed. To
      investigate the efficiency for the post-exposure treatment of rabies, the details
      of 244 rabies patients, including their anti-rabies treatment of injuries or
      related incidents, were ascertained in Guangdong provincial jurisdiction. The
      risk factors to which the patients were predisposed or the regimens given to 80
      patients who received any type of PEP were analysed to identify the reasons for
      the PEP failures. RESULTS: The results from analysis of the large number of human
      rabies cases showed that rabies in China was largely under control during the
      period 1990-1996. However, there has been a large jump in the number of reported
      rabies cases since 2001 up to a new peak (with an incidence rate of 0.20 per
      100000 people) that was reached in 2004, and where the level has remained until
      present. Then, we analysed the PEP in 244 rabies cases collected in the Guangdong
      province in 2003 and 2004, and found that 67.2% of the patients did not seek
      medical services or did not receive any PEP. Further analysis of PEP for the 80
      rabies patients who received any type of PEP indicated that almost all of the
      patients did not receive proper or timely treatment on the wounds or post
      exposure vaccination or rabies immunoglobulins. CONCLUSION: While the issue of
      under-reporting of rabies in previous years may well be a factor in the apparent
      upwards trend of human rabies in recent years, the analysis of PEP in the
      Guangdong province provides evidence that suggests that the failure to receive
      PEP was a major factor in the number of human cases in China. Thus, the data
      underline the need for greatly improved availability and timely application of
      high-quality anti-rabies biologicals, both vaccines and immunoglobulins, in the
      treatment of human bite victims. Controlling dog rabies through pet vaccination
      schemes may also play a huge role in reducing the rate of human exposure.
      Education of the public, health care staff and veterinarians will also help to
      change the current situation.

PMID- 18717990
TI  - Acute maternal stress in pregnancy and schizophrenia in offspring: a cohort
      prospective study.
AB  - Schizophrenia has been linked with intrauterine exposure to maternal stress due
      to bereavement, famine and major disasters. Recent evidence suggests that human
      vulnerability may be greatest in the first trimester of gestation and rodent
      experiments suggest sex specificity. We aimed to describe the consequence of an
      acute maternal stress, through a follow-up of offspring whose mothers were
      pregnant during the Arab-Israeli war of 1967. A priori, we focused on gestational
      month and offspring's sex. METHOD: In a pilot study linking birth records to
      Israel's Psychiatric Registry, we analyzed data from a cohort of 88,829 born in
      Jerusalem in 1964-76. Proportional hazards models were used to estimate the
      relative risk (RR) of schizophrenia, according to month of birth, gender and
      other variables, while controlling for father's age and other potential
      confounders. Other causes of hospitalized psychiatric morbidity (grouped
      together) were analyzed for comparison. RESULTS: There was a raised incidence of
      schizophrenia for those who were in the second month of fetal life in June 1967
      (RR = 2.3, 1.1-4.7), seen more in females (4.3, 1.7-10.7) than in males (1.2, 0.4
      3.8). Results were not explained by secular or seasonal variations, altered birth
      weight or gestational age. For other conditions, RRs were increased in offspring
      who had been in the third month of fetal life in June 1967 (2.5, 1.2-5.2), also
      seen more in females (3.6, 1.3-9.7) than males (1.8, 0.6-5.2). CONCLUSION: These
      findings add to a growing literature, in experimental animals and humans,
      attributing long term consequences for offspring of maternal gestational stress.
      They suggest both a sex-specificity and a relatively short gestational time
      window for gestational effects on vulnerability to schizophrenia.

PMID- 18717991
TI  - Validation of a survey methodology for gastroesophageal reflux disease in China.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) causes a wide range of
      clinical symptoms and potentially serious complications, but epidemiological data
      about GERD in China are limited. The aim of this pilot study was to develop and
      validate a methodology for the epidemiological study of GERD in China. METHODS:
      Regionally stratified, randomized samples of Shanghai residents (n = 919)
      completed Mandarin translations of the Reflux Disease Questionnaire (RDQ), GERD
      Impact Scale, Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire and
      36-item Short Form Health Survey (SF-36). Reliability and construct validity were
      tested by appropriate statistical analyses. RESULTS: The response rate was 86%.
      The test-retest reliability coefficients for the RDQ, GERD Impact Scale, QOLRAD
      and SF-36 were 0.80, 0.71, 0.93 and 0.96, respectively, and Cronbach's alpha
      coefficients were 0.86, 0.80, 0.98 and 0.90, respectively. Dimension scores were
      highly correlated with the total scores for the QOLRAD and SF-36, and factor
      analysis showed credible construct validity for the RDQ, GERD Impact Scale and SF
      36. The RDQ GERD score was significantly negatively correlated with QOLRAD
      dimensions of food and drink problems and social functioning, and was
      significantly negatively correlated with all dimensions of the SF-36. All eight
      of the SF-36 dimensions were significantly correlated with the QOLRAD total
      score. CONCLUSION: This study developed and tested a successful survey
      methodology for the investigation of GERD in China. The questionnaires used
      demonstrated credible reliability and construct validity, supporting their use in
      larger epidemiological surveys of GERD in China.

PMID- 18717992
TI  - Molecular evolution of neuropeptides in the genus Drosophila.
AB  - BACKGROUND: Neuropeptides comprise the most diverse group of neuronal signaling
      molecules. They often occur as multiple sequence-related copies within single
      precursors (the prepropeptides). These multiple sequence-related copies have not
      arisen by gene duplication, and it is debated whether they are mutually redundant
      or serve specific functions. The fully sequenced genomes of 12 Drosophila species
      provide a unique opportunity to study the molecular evolution of neuropeptides.
      RESULTS: We data-mined the 12 Drosophila genomes for homologs of neuropeptide
      genes identified in Drosophila melanogaster. We then predicted peptide precursors
      and the neuropeptidome, and biochemically identified about half of the predicted
      peptides by direct mass spectrometric profiling of neuroendocrine tissue in four
      species covering main phylogenetic lines of Drosophila. We found that all species
      have an identical neuropeptidome and peptide hormone complement. Calculation of
      amino acid distances showed that ortholog peptide copies are highly sequence
      conserved between species, whereas the observed sequence variability between
      peptide copies within single precursors must have occurred prior to the
      divergence of the Drosophila species. CONCLUSION: We provide a first genomic and
      chemical characterization of fruit fly neuropeptides outside D. melanogaster. Our
      results suggest that neuropeptides including multiple peptide copies are under
      stabilizing selection, which suggests that multiple peptide copies are
      functionally important and not dispensable. The last common ancestor of
      Drosophila obviously had a set of neuropeptides and peptide hormones identical to
      that of modern fruit flies. This is remarkable, since drosophilid flies have
      adapted to very different environments.

PMID- 18717993
TI  - Mediastinal plasmacytoma with multiple myeloma presenting as a diagnostic
      dilemma.
AB  - Plasmacytoma are extramedullary accumulations of plasma cells. Most
      extramedullary Plasmacytomas are associated with the upper respiratory tract. The
      mediastinum is rarely involved. We report a rare case of mediastinal plasmacytoma
      with multiple myeloma. The patient is 66 year old woman presented with bone pains
      and mediastinal mass on CT scan and MRI. The preliminary diagnosis of occult lung
      cancer with mediastinal involvement, and widespread skeletal metastasis was made,
      although lymphoproliferative disorder along with germ cell tumor was also kept in
      differentials.The diagnosis of mediastinal plasmacytoma with multiple myeloma was
      made after extensive investigations.

PMID- 18717994
TI  - Midkine promoter-based conditionally replicative adenovirus therapy for midkine
      expressing human pancreatic cancer.
AB  - BACKGROUND: To develop a novel therapeutic strategy for human pancreatic cancer
      using a midkine promoter-based conditionally replicating adenovirus. METHODS: We
      examined midkine mRNA expression and midkine protein expression by seven human
      pancreatic cancer cell lines (AsPC-1, BxPC-3, CFPAC-1, HPAC, MIAPaCa-2, PANC-1,
      and Suit-2), as well as by non-cancerous pancreatic tissue and pancreatic
      cancers. Midkine promoter activity was measured in cancer cell lines by the dual
      luciferase reporter assay. Adenoviral transduction efficiency was assessed by
      fluorescent staining of cancer cell lines using adenovirus type 5 containing the
      green fluorescent protein gene (Ad5GFP). Replication of adenovirus type 5
      containing the 0.6 kb midkne promoter (Ad5MK) was assessed by the detection of E1
      protein in cancer cell lines. The cytotoxicity of Ad5MK for cancer cells was
      evaluated from the extent of growth inhibition after viral infection. Infection
      and replication were also assessed in nude mice with subcutaneous Suit-2 tumors
      by intratumoral injection of Ad5MK, Ad5GFP, or vehicle. E1a mRNA expression in
      the treated tumors and expression of the replication-specific adenoviral hexon
      protein were evaluated. Finally, the anti-tumor activity of Ad5MK against
      intraperitoneal xenografts of Suit-2 pancreatic cancer cells was examined after
      intraperitoneal injection of the virus. RESULTS: Both midkine mRNA expression and
      midkine protein expression were strong in AsPC-1 and CFPAC-1 cell liens, moderate
      in BxPC-3, HPAC, and Suit-2 cell lines, and weak in PANC-1 and MIAPaCa-2 cell
      lines. Expression of midkine mRNA was significantly stronger in pancreatic
      cancers than in non-cancerous pancreatic tissues. The relative luciferase
      activity mediated by the 0.6 kb midkne fragment in AsPC-1, PANC-1, and Suit-2
      cell lines was approximately 6 to 20 times greater than that in midkne-negative
      MIAPaCa-2 cell lines. Pancreatic cancer cell lines exhibited a heterogeneous
      adenoviral transduction profile. E1A expression was higher in cell lines with
      strong midkine expression than in cell lines with weak midkine expression. Ad5MK
      showed much greater cytotoxicity for midkine-expressing Suit-2 and PANC-1 cell
      lines than for midkine-negative MIAPaCa-2 cell lines. In the Suit-2 subcutaneous
      xenograft model, expression of E1A was detected in Ad5MK-treated tumors, but not
      in untreated and Ad5GFP-treated tumors. In the Suit-2 intraperitoneal xenograft
      model, the Ad5MK group survived for significantly longer than the Ad5GFP, PBS,
      and untreated groups. CONCLUSION: Ad5MK has an anti-tumor effect against human
      pancreatic cancer cell lines that express midkine mRNA. Midkine promoter-based
      conditionally replicative adenovirus might be a promising new gene therapy for
      pancreatic cancer.

PMID- 18717995
TI  - Increased deposition of C3b on red cells with low CR1 and CD55 in a malaria
      endemic region of western Kenya: implications for the development of severe
      anemia.
AB  - BACKGROUND: Severe anemia due to Plasmodium falciparum malaria is a major cause
      of mortality among young children in western Kenya. The factors that lead to the
      age-specific incidence of this anemia are unknown. Previous studies have shown an
      age-related expression of red cell complement regulatory proteins, which protect
      erythrocytes from autologous complement attack and destruction. Our primary
      objective was to determine whether in a malaria-endemic area red cells with low
      levels of complement regulatory proteins are at increased risk for complement
      (C3b) deposition in vivo. Secondarily, we studied the relationship between red
      cell complement regulatory protein levels and hemoglobin levels. METHODS: Three
      hundred and forty-two life-long residents of a malaria-holoendemic region of
      western Kenya were enrolled in a cross-sectional study and stratified by age. We
      measured red cell C3b, CR1, CD55, and immune complex binding capacity by flow
      cytometry. Individuals who were positive for malaria were treated and blood was
      collected when they were free of parasitemia. Analysis of variance was used to
      identify independent variables associated with the %C3b-positive red cells and
      the hemoglobin level. RESULTS: Individuals between the ages of 6 and 36 months
      had the lowest red cell CR1, highest %C3b-positive red cells, and highest
      parasite density. Malaria prevalence also reached its peak within this age group.
      Among children </= 24 months of age the %C3b-positive red cells was usually
      higher in individuals who were treated for malaria than in uninfected individuals
      with similarly low red cell CR1 and CD55. The variables that most strongly
      influenced the %C3b-positive red cells were age, malaria status, and red cell
      CD55 level. Although it did not reach statistical significance, red cell CR1 was
      more important than red cell CD55 among individuals treated for malaria. The
      variables that most strongly influenced the hemoglobin level were age, the %C3b
      positive red cells, red cell CR1, and red cell CD55. CONCLUSION: Increasing
      malaria prevalence among children >6 to <or= 36 months of age in western Kenya,
      together with low red cell CR1 and CD55 levels, results in increased C3b
      deposition on red cells and low hemoglobin. The strong contribution of age to C3b
      deposition suggests that there are still additional unidentified age-related
      factors that increase the susceptibility of red cells to C3b deposition and
      destruction.

PMID- 18717996
TI  - The pathophysiology of malarial anaemia: where have all the red cells gone?
AB  - Malarial anaemia is an enormous public health problem in endemic areas and occurs
      predominantly in children in the first 3 years of life. Anaemia is due to both a
      great increase in clearance of uninfected cells and a failure of an adequate bone
      marrow response. Odhiambo, Stoute and colleagues show how the age distribution of
      malarial anaemia and the haemolysis of red blood cells may be linked by an age
      dependent increase in the capacity of red blood cells to inactivate complement
      components absorbed or deposited directly on to the surface of the red blood
      cell. In this commentary, we discuss what has been established about the role of
      complement deposition on the surface of red blood cells in the pathology of
      malarial anaemia, how genetic polymorphisms of the complement control proteins
      influence the outcome of malaria infection and how the findings of Odhiambo,
      Stoute and colleagues and others shed light on the puzzling age distribution of
      different syndromes of severe malaria.

PMID- 18717997
TI  - Development of a health care utilisation data-based index for rheumatoid
      arthritis severity: a preliminary study.
AB  - INTRODUCTION: Health care utilisation ('claims') databases contain information
      about millions of patients and are an important source of information for a
      variety of study types. However, they typically do not contain information about
      disease severity. The goal of the present study was to develop a health care
      claims index for rheumatoid arthritis (RA) severity using a previously developed
      medical records-based index for RA severity (RA medical records-based index of
      severity [RARBIS]). METHODS: The study population consisted of 120 patients from
      the Veteran's Administration (VA) Health System. We previously demonstrated the
      construct validity of the RARBIS and established its convergent validity with the
      Disease Activity Score (DAS28). Potential claims-based indicators were entered
      into a linear regression model as independent variables and the RARBIS as the
      dependent variable. The claims-based index for RA severity (CIRAS) was created
      using the coefficients from models with the highest coefficient of determination
      (R2) values selected by automated modelling procedures. To compare our claims
      based index with our medical records-based index, we examined the correlation
      between the CIRAS and the RARBIS using Spearman non-parametric tests. RESULTS:
      The forward selection models yielded the highest model R2 for both the RARBIS
      with medications (R2 = 0.31) and the RARBIS without medications (R2 = 0.26).
      Components of the CIRAS included tests for inflammatory markers, number of
      chemistry panels and platelet counts ordered, rheumatoid factor, the number of
      rehabilitation and rheumatology visits, and Felty's syndrome diagnosis. The CIRAS
      demonstrated moderate correlations with the RARBIS with medication and the RARBIS
      without medication sub-scales. CONCLUSION: We developed the CIRAS that showed
      moderate correlations with a previously validated records-based index of
      severity. The CIRAS may serve as a potentially important tool in adjusting for RA
      severity in pharmacoepidemiology studies of RA treatment and complications using
      health care utilisation data.

PMID- 18717998
TI  - Spatial prediction of Plasmodium falciparum prevalence in Somalia.
AB  - BACKGROUND: Maps of malaria distribution are vital for optimal allocation of
      resources for anti-malarial activities. There is a lack of reliable contemporary
      malaria maps in endemic countries in sub-Saharan Africa. This problem is
      particularly acute in low malaria transmission countries such as those located in
      the horn of Africa. METHODS: Data from a national malaria cluster sample survey
      in 2005 and routine cluster surveys in 2007 were assembled for Somalia. Rapid
      diagnostic tests were used to examine the presence of Plasmodium falciparum
      parasites in finger-prick blood samples obtained from individuals across all age
      groups. Bayesian geostatistical models, with environmental and survey covariates,
      were used to predict continuous maps of malaria prevalence across Somalia and to
      define the uncertainty associated with the predictions. RESULTS: For analyses the
      country was divided into north and south. In the north, the month of survey,
      distance to water, precipitation and temperature had no significant association
      with P. falciparum prevalence when spatial correlation was taken into account. In
      contrast, all the covariates, except distance to water, were significantly
      associated with parasite prevalence in the south. The inclusion of covariates
      improved model fit for the south but not for the north. Model precision was
      highest in the south. The majority of the country had a predicted prevalence of <
      5%; areas with > or = 5% prevalence were predominantly in the south. CONCLUSION:
      The maps showed that malaria transmission in Somalia varied from hypo- to meso
      endemic. However, even after including the selected covariates in the model,
      there still remained a considerable amount of unexplained spatial variation in
      parasite prevalence, indicating effects of other factors not captured in the
      study. Nonetheless the maps presented here provide the best contemporary
      information on malaria prevalence in Somalia.

PMID- 18717999
TI  - Organizational culture, team climate and diabetes care in small office-based
      practices.
AB  - BACKGROUND: Redesigning care has been proposed as a lever for improving chronic
      illness care. Within primary care, diabetes care is the most widespread example
      of restructured integrated care. Our goal was to assess to what extent important
      aspects of restructured care such as multidisciplinary teamwork and different
      types of organizational culture are associated with high quality diabetes care in
      small office-based general practices. METHODS: We conducted cross-sectional
      analyses of data from 83 health care professionals involved in diabetes care from
      30 primary care practices in the Netherlands, with a total of 752 diabetes
      mellitus type II patients participating in an improvement study. We used self
      reported measures of team climate (Team Climate Inventory) and organizational
      culture (Competing Values Framework), and measures of quality of diabetes care
      and clinical patient characteristics from medical records and self-report. We
      conducted multivariate analyses of the relationship between culture, climate and
      HbA1c, total cholesterol, systolic blood pressure and a sum score on process
      indicators for the quality of diabetes care, adjusting for potential patient- and
      practice level confounders and practice-level clustering. RESULTS: A strong group
      culture was negatively associated to the quality of diabetes care provided to
      patients (beta = -0.04; p = 0.04), whereas a more 'balanced culture' was
      positively associated to diabetes care quality (beta = 5.97; p = 0.03). No
      associations were found between organizational culture, team climate and clinical
      patient outcomes. CONCLUSION: Although some significant associations were found
      between high quality diabetes care in general practice and different
      organizational cultures, relations were rather marginal. Variation in clinical
      patient outcomes could not be attributed to organizational culture or teamwork.
      This study therefore contributes to the discussion about the legitimacy of the
      widespread idea that aspects of redesigning care such as teamwork and culture can
      contribute to higher quality of care. Future research should preferably combine
      quantitative and qualitative methods, focus on possible mediating or moderating
      factors and explore the use of instruments more sensitive to measure such complex
      constructs in small office-based practices.

PMID- 18718000
TI  - Extrinsic post burn peri-anal contracture leading to sub acute intestinal
      obstruction: A case report.
AB  - Peri-anal contracture lead to intestinal obstruction whenever there is
      involvement of anal orifice. In this case anus and peri-anal skin up to two cm
      was normal; however both gluteal folds were fused because of post burn scar
      leaving a very small opening which lead to faecal impaction and sub acute
      intestinal obstruction.

PMID- 18718001
TI  - Disseminated peritoneal hydatidosis following blunt abdominal trauma: A case
      report.
AB  - A middle age lady presented with abdominal pain was diagnosed to have multiple
      peritoneal and hepatic hydatid cysts on CT scan. Retrospectively she was found to
      have suffered blunt abdominal trauma.

PMID- 18718002
TI  - Computerized tomographic angiography for preoperative assessment of the
      superficial temporal artery for external carotid artery to internal carotid
      artery bypass: Case illustration.
AB  - INTRODUCTION: While catheter angiography has traditionally been used to assess
      the caliber and course of the superficial temporal artery prior to its use as a
      conduit for external carotid artery to internal carotid artery (EC-IC) bypass,
      computed tomographic angiography (CTA) has become increasingly used in the
      diagnostic assessment of cerebral vasculature. We demonstrate the application of
      CTA for evaluation of the superficial temporal artery as a vascular conduit for
      EC-IC bypass. CASE PRESENTATION: A female in the fourth decade of life presented
      with the chief complaint of headache. CTA of the Circle of Willis revealed an
      unruptured fusiform aneurysm of the M1 segment of the right middle cerebral
      artery (MCA). We performed CTA for the preoperative assessment of the STA for a
      putative EC-IC bypass procedure, and correlated this to conventional external
      carotid angiography. Reformatted CTA provided excellent surface visualization of
      the STA and its course in relationship to the cranial and zygomatic surfaces, and
      correlated well with findings on the conventional angiogram. CONCLUSION: CTA may
      eventually prove sufficient for use in assessing the STA in preparation for EC-IC
      bypass.

PMID- 18718003
TI  - Identification of suitable endogenous control genes for microRNA gene expression
      analysis in human breast cancer.
AB  - The discovery of microRNAs (miRNAs) added an extra level of intricacy to the
      already complex system regulating gene expression. These single-stranded RNA
      molecules, 18-25 nucleotides in length, negatively regulate gene expression
      through translational inhibition or mRNA cleavage. The discovery that aberrant
      expression of specific miRNAs contributes to human disease has fueled much
      interest in profiling the expression of these molecules. Real-time quantitative
      PCR (RQ-PCR) is a sensitive and reproducible gene expression quantitation
      technique which is now being used to profile miRNA expression in cells and
      tissues. To correct for systematic variables such as amount of starting template,
      RNA quality and enzymatic efficiencies, RQ-PCR data is commonly normalised to an
      endogenous control (EC) gene, which ideally, is stably-expressed across the test
      sample set. A universal endogenous control suitable for every tissue type,
      treatment and disease stage has not been identified and is unlikely to exist, so,
      to avoid introducing further error in the quantification of expression data it is
      necessary that candidate ECs be validated in the samples of interest. While ECs
      have been validated for quantification of mRNA expression in various experimental
      settings, to date there is no report of the validation of miRNA ECs for
      expression profiling in breast tissue. In this study, the expression of five
      miRNA genes (let-7a, miR-10b, miR-16, miR-21 and miR-26b) and three small
      nucleolar RNA genes (RNU19, RNU48 and Z30) was examined across malignant, benign
      and normal breast tissues to determine the most appropriate normalisation
      strategy. This is the first study to identify reliable ECs for analysis of miRNA
      by RQ-PCR in human breast tissue.

PMID- 18718004
TI  - Comparison of the discriminative ability of a generic and a condition-specific
      OHRQoL measure in adolescents with and without normative need for orthodontic
      treatment.
AB  - BACKGROUND: At present, there is no evidence on whether using condition-specific
      Oral Health-Related Quality of Life (OHRQoL) measures provides more reliable
      information than generic measures for needs assessment. Therefore, the objective
      was to assess the discriminative ability of one generic and one condition
      specific OHRQoL measure, namely, respectively, the short form of the Oral Health
      Impact Profile (OHIP-14) and the Condition-Specific form of the Oral Impacts on
      Daily Performances (CS-OIDP) attributed to malocclusion, between adolescents with
      and without normative need for orthodontic treatment. METHODS: 200 16-17-year-old
      adolescents were randomly selected from 957 schoolchildren attending a Sixth Form
      College in London, United Kingdom. The impact of their oral conditions on quality
      of life during the last 6 months was assessed using two OHRQoL measures; OHIP-14
      and OIDP. Adolescents were also examined for normative orthodontic treatment need
      using the Index of Orthodontic Treatment Need (IOTN) and the Dental Aesthetic
      Index (DAI). Discriminative ability was assessed comparing the overall scores and
      prevalence of oral impacts, calculated using each OHRQoL measure, between
      adolescents with and without normative need. Using the prevalence of oral impacts
      allowed adjusting for covariates. RESULTS: There were significant differences in
      overall scores for CS-OIDP attributed to malocclusion between adolescents with
      and without normative need for orthodontic treatment when IOTN or DAI were used
      to define need (p = 0.029 or 0.011 respectively), and in overall scores for OHIP
      14 when DAI, but not IOTN was used to define need (p = 0.029 and 0.080
      respectively). For the prevalence of impacts, only the prevalence of CS-OIDP
      attributed to malocclusion differed significantly between adolescents with and
      without normative need, even after adjusting for covariates (p = 0.017 and 0.049
      using IOTN and DAI to define need). CONCLUSION: CS-OIDP attributed to
      malocclusion was better able than OHIP-14 to discriminate between adolescents
      with and without normative needs for orthodontic treatment.

PMID- 18718005
TI  - Euthanasia of Danish dairy cows evaluated in two questionnaire surveys.
AB  - BACKGROUND: Mortality risk in Danish dairy cows has more than doubled since 1990
      (from 2% in 1990 to 5% in 2005). Until now, registrations about dead cows in the
      Danish Cattle Database have not included information about whether the cow died
      unassisted or was euthanized. METHODS: We interviewed a random sample of 196
      Danish dairy farmers that had reported a dead cow to the Danish Cattle Database
      in 2002 and 196 dairy farmers that had reported a dead cow in 2006. Our
      objectives were to evaluate the proportion of euthanized cows, changes in the
      behaviour of farmers regarding euthanasia of cows over the years and possible
      reasons for these changes. RESULTS: It seems that the threshold for euthanasia of
      cows among farmers has changed. Farmers generally reported a lower threshold for
      euthanasia compared to 5-10 years ago. CONCLUSION: The threshold for euthanasia
      of cows has, according to the dairy farmers, become lower. This might have
      positive impacts on animal welfare as more seriously ill cows are euthanized in
      the herds and not put through a period of suffering associated with disease and
      treatment or transported to a slaughterhouse in poor condition.

PMID- 18718006
TI  - Erythromycin lacks colon prokinetic effect in children with functional
      gastrointestinal disorders: a retrospective study.
AB  - BACKGROUND: Motilin, a peptide hormone has a direct excitatory effect on circular
      smooth muscle strips derived from the human colon. Reduced plasma motilin
      concentration has been reported in adults with chronic constipation.
      Erythromycin, a non-peptide motilin receptor agonist, induces phase 3 of the
      migrating motor complex (MMC) in the antro-duodenum and also reduces oro-cecal
      transit time. A pediatric study has reported an improvement in clinical symptoms
      of constipation following erythromycin administration, but the effect on colon
      motility in children has not been formally evaluated. We used colon manometry to
      study the effect of intravenous erythromycin lactobionate at 1 mg/kg on colon
      motility in ten children. METHODS: We selected patients with normal antroduodenal
      and colon manometry studies that were performed simultaneously. All studies were
      performed for clinically indicated reasons. We quantified the effect of
      erythromycin on colon contraction by calculating the area under the curve (AUC).
      RESULTS: The mean (SE of mean) AUC in the colon during the fasting, post
      erythromycin and postprandial phases of the study was 2.1 mmHg/sec (0.35), 0.99
      mmHg/sec (0.17) and 3.05 mmHg/sec (0.70) respectively. The AUC following
      erythromycin was significantly less compared to the fasting phase of the study (p
      < 0.01). CONCLUSION: Erythromycin lacks colon prokinetic effect in children with
      chronic constipation evaluated by colon manometry.

PMID- 18718008
TI  - Maternal mortality in South Africa in 2001: From demographic census to
      epidemiological investigation.
AB  - BACKGROUND: Maternal mortality remains poorly researched in Africa, and is likely
      to worsen dramatically as a consequence of HIV/AIDS. METHODS: The 2001 census of
      South Africa included a question on deaths in the previous 12 months, and two
      questions on external causes and maternal mortality, defined as "pregnancy
      related deaths". A microdata sample from the census permits researchers to assess
      levels and differentials in maternal mortality, in a country severely affected by
      high death rates from HIV/AIDS and from external causes. RESULTS: After
      correcting for several minor biases, our estimate of the Maternal Mortality Ratio
      (MMR) in 2001 was 542 per 100,000 live births. This level is much higher than
      previous estimates dating from pre-HIV/AIDS times. This high level occurred
      despite a relatively low proportion of maternal deaths (6.4%) among deaths of
      women aged 15-49 years, and was due to the astonishingly high level of adult
      mortality, some 4.7 times higher than expected from mortality below age 15 or
      above age 50. The main reasons for these excessive levels were HIV/AIDS and
      external causes of deaths. Our regional estimates of MMR were found to be
      consistent with other findings in the Cape Town area, and with the Agincourt DSS.
      The differentials in MMR were considerable: 1 to 9.2 for population groups
      (race), 1 to 3.2 for provinces, and 1 to 2.4 for levels of education.
      Relationship with income and wealth were complex, with highest values for middle
      income and middle wealth index. The effect of urbanization was small, and
      reversed in a multivariate analysis. Higher risks in provinces were not
      necessarily associated with lower income, lower education or higher proportions
      of home delivery, but correlated primarily with the prevalence of HIV/AIDS.
      CONCLUSION: Demographic census microdata offer the opportunity to conduct an
      epidemiologic analysis of maternal mortality. In the case of South Africa, the
      level of MMR increased dramatically over the past 10 years, most likely because
      of HIV/AIDS. Indirect causes of maternal deaths appear much more important than
      direct obstetric causes. The MMR appears no longer to be a reliable measure of
      the quality of obstetric care or a measure of safe motherhood.

PMID- 18718007
TI  - Misoprostol in addition to routine treatment of postpartum hemorrhage: a hospital
      based randomized-controlled trial in Karachi, Pakistan.
AB  - BACKGROUND: Postpartum hemorrhage (PPH) remains a major killer of women
      worldwide. Standard uterotonic treatments used to control postpartum bleeding do
      not always work and are not always available. Misoprostol's potential as a
      treatment option for PPH is increasingly known, but its use remains ad hoc and
      available evidence does not support the safety or efficacy of one particular
      regimen. This study aimed to determine the adjunct benefit of misoprostol when
      combined with standard oxytocics for PPH treatment. METHODS: A randomized
      controlled trial was conducted in four Karachi hospitals from December 2005 -
      April 2007 to assess the benefit of a 600 mcg dose of misoprostol given
      sublingually in addition to standard oxytocics for postpartum hemorrhage
      treatment. Consenting women had their blood loss measured after normal vaginal
      delivery and were enrolled in the study after losing more than 500 ml of blood.
      Women were randomly assigned to receive either 600 mcg sublingual misoprostol or
      matching placebo in addition to standard PPH treatment with injectable oxytocics.
      Both women and providers were blinded to the treatment assignment. Blood loss was
      collected until active bleeding stopped and for a minimum of one hour after PPH
      diagnosis. Total blood loss, hemoglobin measures, and treatment outcomes were
      recorded for all participants. RESULTS: Due to a much lower rate of PPH than
      expected (1.2%), only sixty-one patients were diagnosed and treated for their PPH
      in this study, and we were therefore unable to measure statistical significance
      in any of the primary endpoints. The addition of 600 mcg sublingual misoprostol
      to standard PPH treatments does, however, suggest a trend in reduced postpartum
      blood loss, a smaller drop in postpartum hemoglobin, and need for fewer
      additional interventions. Women who bled less overall had a significantly smaller
      drop in hemoglobin and received fewer additional interventions. There were no
      hysterectomies or maternal deaths among study participants. The rate of transient
      shivering and fever was significantly higher among women receiving misoprostol
      CONCLUSION: A 600 mcg dose of misoprostol given sublingually shows promise as an
      adjunct treatment for PPH and its use should continue to be explored for its life
      saving potential in the care of women experiencing PPH. TRIAL REGISTRATION:
      Clinical trials.gov, Registry No. NCT00116480.

PMID- 18718009
TI  - Disruption of the thrombospondin-2 gene alters the lamellar morphology but does
      not permit vascularization of the adult mouse lumbar disc.
AB  - INTRODUCTION: The biological basis for the avascular state of the intervertebral
      disc is not well understood. Previous work has suggested that the presence of
      thrombospondin-1 (TSP-1), a matricellular protein, in the outer annulus reflects
      a role for this protein in conferring an avascular status to the disc. In the
      present study we have examined thrombospondin-2 (TSP-2), a matricellular protein
      with recognized anti-angiogenic activity in vivo and in vitro. METHODS: We
      examined both the location and expression of TSP-2 in the human disc, and its
      location in the disc and bordering soft tissues of 5-month-old normal wild-type
      (WT) mice and of mice with a targeted disruption of the TSP-2 gene.
      Immunohistochemistry and quantitative histology were utilized in this study.
      RESULTS: TSP-2 was found to be present in some, but not all, annulus cells of the
      human annulus and the mouse annulus. Although there was no difference in the
      number of disc cells in the annulus of TSP-2-null mice compared with that of WT
      animals, polarized light microscopy revealed a more irregular lamellar collagen
      structure in null mouse discs compared with WT mouse discs. Additionally,
      vascular beds at the margins of discs of TSP-2-null mice were substantially more
      irregular than those of WT animals. Counts of platelet endothelial cell adhesion
      molecule-1-positive blood vessels in the tissue margin bordering the ventral
      annulus showed a significantly larger vascular bed in the tissue bordering the
      disc of TSP-2-null mice compared with that of WT mice (P = 0.0002). There was,
      however, no vascular ingrowth into discs of the TSP-2-null mice. CONCLUSION:
      These data confirm a role for TSP-2 in the morphology of the disc and suggest the
      presence of other inhibitors of angiogenesis in the disc. We have shown that
      although an increase in vasculature was present in the TSP-2-null tissue in the
      margin of the disc, vascular ingrowth into the body of the disc did not occur.
      Our results point to the need for future research to understand the transition
      from the well-vascularized status of the fetal and young discs to the avascular
      state of the adult human disc or the small mammalian disc.

PMID- 18718010
TI  - Adaptation of the Emotional Contagion Scale (ECS) and gender differences within
      the Greek cultural context.
AB  - BACKGROUND: The Emotional Contagion Scale (ECS) is a self-report scale used to
      measure individual differences in susceptibility to converge towards the emotions
      expressed by others. The main aim of the present paper was to examine the
      psychometric properties of the Greek translation of the scale. METHODS: The Greek
      ECS was completed by 691 undergraduate students (312 males and 379 females). To
      investigate the factor structure of the ECS, principal components analysis (PCA)
      was used. RESULTS: The results showed that a four-factor model was tenable.
      Regarding homogeneity, the Greek ECS version showed acceptable results for the
      full scale (alpha = 0.74) but not for all subscales. Gender differences were also
      identified concerning the susceptibility to emotional contagion between men and
      women. Women score significantly higher than men for all the different emotions
      described by the ECS (love, happiness, sadness) except the anger emotion, where
      there was no significant difference. CONCLUSION: The Greek version of the ECS
      showed good psychometric properties. It can be used to assess susceptibility to
      emotional contagion in correlation with psychopathological processes, mood and
      anxiety disorders primarily. The usefulness of the ECS in the fields of group
      psychotherapy and health psychology is also under consideration. Further
      investigation is needed in all these areas.

PMID- 18718011
TI  - Optimization of capsid-incorporated antigens for a novel adenovirus vaccine
      approach.
AB  - Despite the many potential advantages of Ad vectors for vaccine application, the
      full utility of current Ad vaccines may be limited by the host anti-vector immune
      response. Direct incorporation of antigens into the adenovirus capsid offers a
      new and exciting approach for vaccination strategies; this strategy exploits the
      inherent antigenicity of the Ad vector. Critical to exploiting Ad in this new
      context is the placement of antigenic epitopes within the major Ad capsid
      protein, hexon. In our current study we illustrate that we have the capability to
      place a range of antigenic epitopes within Ad5 capsid protein hexon hypervariable
      regions (HVRs) 2 or 5, thus producing viable Ad virions. Our data define the
      maximal incorporation size at HVR2 or HVR5 as it relates to identical antigenic
      epitopes. In addition, this data suggests that Ad5 HVR5 is more permissive to a
      range of insertions. Most importantly, repeated administration of our hexon
      modified viruses resulted in a secondary anti-antigen response, whereas minimal
      secondary effect was present after administration of Ad5 control. Our study
      describes antigen placement and optimization within the context of the capsid
      incorporation approach of Ad vaccine employment, thereby broadening this new
      methodology.

PMID- 18718012
TI  - Increasing physical activity and decreasing sedentary activity in adolescent
      girls--the Incorporating More Physical Activity and Calcium in Teens (IMPACT)
      study.
AB  - BACKGROUND: Lack of regular physical activity and consequent sub-optimal bone
      mass acquisition in youth has been implicated as a primary cause of adult-onset
      osteoporosis. IMPACT was a behavioral theory-based 1 1/2 year randomized
      controlled field study aimed at increasing bone accretion in middle school girls.
      The objective of this study was to determine the intervention effects of the
      IMPACT program upon key physical and sedentary activity endpoints among schools
      that participated in the IMPACT study. Endpoints examined included weight bearing
      physical activity (WBPA); moderate to vigorous physical activity (MVPA); vigorous
      physical activity (VPA); MET (metabolic equivalent) - weighted WBPA and MVPA;
      sedentary activity; before/after-school physical activity; and weekend physical
      activity. METHODS: Primary data analysis using a pretest-posttest control group
      design was conducted utilizing mixed model analysis of covariance. Data gathered
      from the IMPACT cohort from 2000-2002 were analyzed to determine baseline versus
      follow-up differences in activity endpoints. Confounders investigated included
      ethnicity, body mass index, menarcheal status, participation in 7th grade
      PE/athletics, friend/familial support and neighborhood safety. RESULTS: Follow-up
      means were higher for participating intervention schools relative to control
      schools for all physical activity variables but were statistically significant
      only for the following variables: daily minutes of vigorous physical activity
      (mean difference between Intervention (I) and Control (C) = 6.00 upward arrow
      minutes, 95% CI = 5.82-6.18, p = 0.05), daily after school activity minutes (mean
      difference between I and C = 8.95 upward arrow minutes, 95% CI = 8.69-9.21, p =
      0.04), and daily weekend activity minutes (mean difference between I and C =
      19.00 upward arrow minutes, 95% CI = 18.40-19.60, p = 0.05). The intervention
      significantly reduced duration of student daily TV/Video watching (mean
      difference between I and C = 12.11 downward arrow minutes, 95% CI = 11.74-12.48,
      p = 0.05) and total daily sedentary activity minutes (mean difference between I
      and C = 16.99 downward arrow minutes, 95% CI = 16.49-17.50, p = 0.04).
      CONCLUSION: A well designed and implemented school based health and physical
      activity intervention can result in a positive influence upon increasing physical
      activity levels and decreasing sedentary activity. Future interventions should
      consider a more structured intervention component to obtain significant changes
      in WBPA.

PMID- 18718013
TI  - Lingual infarction in Wegener's Granulomatosis: a case report and review of the
      literature.
AB  - Wegener's granulomatosis (WG) is a multi-system disease, characterised by the
      triad of necrotising granulomata affecting the upper and lower respiratory
      tracts, disseminated vasculitis and glomerulonephritis. Oral lesions are
      associated with up to 50% of cases, although are rare as a presenting feature.
      The most common oral lesions associated with WG are ulceration and strawberry
      gingivitis. We review the literature regarding oral manifestations of WG and
      present a case of lingual infarction, an extremely rare oral lesion associated
      with WG, in a severe, rapidly progressive and ultimately fatal form of the
      disease.

PMID- 18718014
TI  - Bilateral femoral neck fractures due to transient osteoporosis of pregnancy: a
      case report.
AB  - We describe a case of bilateral femoral neck fractures secondary to transient
      osteoporosis of pregnancy, which were diagnosed after delivery due to the desire
      to avoid ionising radiation. These fractures were presumed to be secondary to
      transient osteoporosis of pregnancy and were treated successfully with internal
      fixation despite delayed presentation. We discuss the role of MRI in the
      evaluation of hip pain in pregnancy.

PMID- 18718015
TI  - Relaxin reduces xenograft tumour growth of human MDA-MB-231 breast cancer cells.
AB  - INTRODUCTION: Relaxin levels are increased in cases of human breast cancer and
      has been shown to promote cancer cell migration in carcinoma cells of the breast,
      prostate gland and thyroid gland. In oestrogen receptor alpha-negative MDA-MB-231
      human breast cancer cells, relaxin was shown to down-regulate the metastasis
      promoting protein S100A4 (metastasin), a highly significant prognostic factor for
      poor survival in breast cancer patients. The cellular mechanisms of relaxin
      exposure in breast cancer cells are not fully understood. The aim of this study
      was to investigate short-term and long-term effects of relaxin on cancer cell
      motility and S100A4 expression and to determine the long-term effects of relaxin
      on in vivo tumour growth in an oestrogen-independent context. METHOD: We have
      established stable transfectants of highly invasive oestrogen-receptor alpha
      negative MDA-MB-231 human breast cancer cells with constitutive expression of
      bioactive H2-relaxin (MDA/RLN2). RLN2 secretion was determined by ELISA. Relaxin
      receptor RXFP1 (Relaxin-family-peptide) was detected by reverse transcription
      (RT) PCR and its activation was assessed by induction of cyclic adenosine
      monophosphate (cAMP). Stable MDA/RLN2 clones and RLN2 treated MDA-MB-231 cells
      were subjected to motility and in vitro-invasion assays. Proliferation was
      assessed in bromodeoxyuridine (BrdU) and MTT assays. S100A4 expression was
      determined by RT-PCR and Western blot. Specific small interfering RNA was
      employed to down-regulate relaxin receptor and S100A4. MDA/EGFP vector control
      and two MDA/RLN2 clones were injected subcutaneously in nude mice to determine
      tumour growth and cancer cell invasiveness in vivo. Xenograft tumour tissues were
      assessed by histology and immunohistochemistry and frozen tissues were used for
      the detection of S100A4 and RLN2. RESULTS: Short-term exposure to relaxin for 24
      hours increased cell motility in a relaxin receptor-dependent manner. This
      increase in cell motility was mediated by S100A4. Long-term exposure to relaxin
      secreted from stable transfectants reduced cell motility and in vitro
      invasiveness. Relaxin decreased cell proliferation and down-regulated cellular
      S100A4 levels in MDA-MB-231 and T47D breast cancer cells. Stable MDA/RLN2
      transfectants produced smaller xenograft tumours containing reduced S100A4
      protein levels in vivo. CONCLUSION: Our results indicate that long-term exposure
      to relaxin confers growth inhibitory and anti-invasive properties in oestrogen
      independent tumours in vivo, which may in part be mediated through a down
      regulation of S100A4.

PMID- 18718016
TI  - Development and validation of a preference based measure derived from the
      Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) for use in cost utility
      analyses.
AB  - BACKGROUND: Pulmonary Hypertension is a severe and incurable disease with poor
      prognosis. A suite of new disease-specific measures--the Cambridge Pulmonary
      Hypertension Outcome Review (CAMPHOR) - was recently developed for use in this
      condition. The purpose of this study was to develop and validate a preference
      based measure from the CAMPHOR that could be used in cost-utility analyses.
      METHODS: Items were selected that covered major issues covered by the CAMPHOR QoL
      scale (activities, travelling, dependence and communication). These were used to
      create 36 health states that were valued by 249 people representative of the UK
      adult population, using the time trade-off (TTO) technique. Data from the TTO
      interviews were analysed using both aggregate and individual level modelling.
      Finally, the original CAMPHOR validation data were used to validate the new
      preference based model. RESULTS: The predicted health state values ranged from
      0.962 to 0.136. The mean level model selected for analyzing the data had good
      explanatory power (0.936), did not systematically over- or underestimate the
      observed mean health state values and showed no evidence of auto correlation in
      the prediction errors. The value of less than 1 reflects a background level of
      ill health in state 1111, as judged by the respondents. Scores derived from the
      new measure had excellent test-retest reliability (0.85) and construct validity.
      The CAMPHOR utility score appears better able to distinguish between WHO
      functional classes (II and III) than the EQ-5D and SF-6D. CONCLUSION: The tariff
      derived in this study can be used to classify an individual into a health state
      based on their responses to the CAMPHOR. The results of this study widen the
      evidence base for conducting economic evaluations of interventions designed to
      improve QoL for patients with PH.

PMID- 18718017
TI  - Transcriptome analysis reveals response regulator SO2426-mediated gene expression
      in Shewanella oneidensis MR-1 under chromate challenge.
AB  - BACKGROUND: Shewanella oneidensis MR-1 exhibits diverse metal ion-reducing
      capabilities and thus is of potential utility as a bioremediation agent.
      Knowledge of the molecular components and regulatory mechanisms dictating
      cellular responses to heavy metal stress, however, remains incomplete. In a
      previous work, the S. oneidensis so2426 gene, annotated as a DNA-binding response
      regulator, was demonstrated to be specifically responsive at both the transcript
      and protein levels to acute chromate [Cr(VI)] challenge. To delineate the
      cellular function of SO2426 and its contribution to metal stress response, we
      integrated genetic and physiological approaches with a genome-wide screen for
      target gene candidates comprising the SO2426 regulon. RESULTS: Inactivation of
      so2426 by an in-frame deletion resulted in enhanced chromate sensitivity and a
      reduced capacity to remove extracellular Cr(VI) relative to the parental strain.
      Time-resolved microarray analysis was used to compare transcriptomic profiles of
      wild-type and SO2426-deficient mutant S. oneidensis under conditions of chromate
      exposure. In total, 841 genes (18% of the arrayed genome) were up- or
      downregulated at least twofold in the Deltaso2426 mutant for at least one of six
      time-point conditions. Hierarchical cluster analysis of temporal transcriptional
      profiles identified a distinct cluster (n = 46) comprised of co-ordinately
      regulated genes exhibiting significant downregulated expression (p < 0.05) over
      time. Thirteen of these genes encoded proteins associated with transport and
      binding functions, particularly those involved in Fe transport and homeostasis
      (e.g., siderophore biosynthetic enzymes, TonB-dependent receptors, and the iron
      storage protein ferritin). A conserved hypothetical operon (so1188-so1189
      so1190), previously identified as a potential target of Fur-mediated repression,
      as well as a putative bicyclomycin resistance gene (so2280) and cation efflux
      family protein gene (so2045) also were repressed in the so2426 deletion mutant.
      Furthermore, the temporal expression profiles of four regulatory genes including
      a cpxR homolog were perturbed in the chromate-challenged mutant. CONCLUSION: Our
      findings suggest a previously unrecognized functional role for the response
      regulator SO2426 in the activation of genes required for siderophore-mediated Fe
      acquisition, Fe storage, and other cation transport mechanisms. SO2426 regulatory
      function is involved at a fundamental molecular level in the linkage between Fe
      homeostasis and the cellular response to chromate-induced stress in S.
      oneidensis.

PMID- 18718018
TI  - Prion protein lacks robust cytoprotective activity in cultured cells.
AB  - BACKGROUND: The physiological function of the cellular prion protein (PrPC)
      remains unknown. However, PrPC has been reported to possess a cytoprotective
      activity that prevents death of neurons and other cells after a toxic stimulus.
      To explore this effect further, we attempted to reproduce several of the assays
      in which a protective activity of PrP had been previously demonstrated in
      mammalian cells. RESULTS: In the first set of experiments, we found that PrP over
      expression had a minimal effect on the death of MCF-7 breast carcinoma cells
      treated with TNF-alpha and Prn-p0/0 immortalized hippocampal neurons (HpL3-4
      cells) subjected to serum deprivation. In the second set of assays, we observed
      only a small difference in viability between cerebellar granule neurons cultured
      from PrP-null and control mice in response to activation of endogenous or
      exogenous Bax. CONCLUSION: Taken together, our results suggest either that
      cytoprotection is not a physiologically relevant activity of PrPC, or that PrPC
      dependent protective pathways operative in vivo are not adequately modeled by
      these cell culture systems. We suggest that cell systems capable of mimicking the
      neurotoxic effects produced in transgenic mice by N-terminally deleted forms of
      PrP or Doppel may represent more useful tools for analyzing the cytoprotective
      function of PrPC.

PMID- 18718019
TI  - Congenital contractures and distinctive phenotypic features consistent with Stuve
      Wiedmann syndrome in a male infant.
AB  - INTRODUCTION: Expressionless face associated with multiple contractures has been
      encountered in an infant. There is a wide range of misconception regarding the
      categorization of children with multiple contractures among different pediatric
      disciplines. The fundamental element in categorizing children with multiple
      contractures is "the etiological understanding". In the absence of concomitant
      neuromuscular disease, however, the search for other reasons is mandatory. Our
      present paper signifies the necessity of proper interpretations of unusual
      clinical and radiographic features. CASE PRESENTATION: We describe a 3-months-old
      infant presented with the phenotypic and the radiographic features consistent
      with the diagnosis of Stuve-Wiedemann syndrome. We report what might be the first
      clinical report of Stuve-Wiedemann syndrome from a consanguineous family in
      Austria. CONCLUSION: Congenital limitations of the hips in a newborn infant raise
      the possibility of " Congenital Hip Dislocation". As congenital hip dislocation
      is a dysplastic process. Here further knowledge by the pediatrician and the
      orthopaedic surgeon is needed. Our present patient appears to constitute a
      distinct pathological entity consistent with Stuve-Wiedemann syndrome (SWS).
      Superti-Furga et al, and Cormier-Daire et al, also suggest that Stuve-Wiedemann
      syndrome and Schwartz-Jampel syndrome type 2 are allelic conditions. We wish to
      stress that, given the rarity of syndromic malformation complex, our impression
      is that it is more common than it is reported.

PMID- 18718020
TI  - Nocardia - Opportunistic chest infection in elderly: A case report.
AB  - In this rare case a non-immunocompromised patient with old Tuberculosis on low
      dose of steroids presents with opportunistic infection of a weakly aerobic gram
      positive acid fast, filamentous bacteria called Nocardia.An 80 year old non
      smoking white female presented with cough, shortness of breath and purulent
      sputum.Initial antibiotics given were not helpful. Later microbial diagnosis was
      Nocardia in sputum sample which was uncommon in a non-immunocompromised. She
      responded to co-trimoxazole therapy.

PMID- 18718022
TI  - Does preoperative analysis of intrahepatic venous anastomoses improve the
      surgeon's intraoperative decision making? Pilot data from a case report.
AB  - BACKGROUND: Three-dimensional (3D) visualization is thought to improve the
      anatomical understanding of clinicians, thus improving patient safety. CASE
      PRESENTATION: A 58-year-old male was admitted to our hospital in April 2007 with
      a suspected metastasis of a sigmoid cancer in the Couinaud segment (CS) 7. The
      anatomical situation of this patient was analyzed using both a CT scan and 3D
      images. The initial CT scan revealed that the proximal part of the middle hepatic
      vein was completely missing and the metastasis in the CS 7 was closely attached
      to the right hepatic vein. After analyzing additional 3D images, it became clear
      that due to the close proximity of metastasis and right hepatic vein, the
      resection of the right hepatic vein was inevitable. Based on this 3D analysis, it
      was decided to perform a right-sided hemihepatectomy. In this case report, 3D
      visualization resulted in a faster and clearer understanding of the unique
      anatomical situation in a patient with complicated liver anatomy than transversal
      CT images. CONCLUSION: The here presented data shows for the first time 3D
      visualization of intravenous anastomoses in the human liver. The information
      offered by 3D visualization is not redundant but rather serves as a true source
      of additional information, indicating the potential benefit of 3D visualization
      in surgical operation planning.

PMID- 18718021
TI  - Conjugated linoleic acid modulation of risk factors associated with
      atherosclerosis.
AB  - Conjugated linoleic acid (CLA) has been the subject of extensive investigation
      regarding its possible benefits on a variety of human diseases. In some animal
      studies, CLA has been shown to have a beneficial effect on sclerotic lesions
      associated with atherosclerosis, be a possible anti-carcinogen, increase feed
      efficiency, and act as a lean body mass supplement. However, the results have
      been inconsistent, and the effects of CLA on atherogenesis appear to be dose-,
      isomer-, tissue-, and species-specific. Similarly, CLA trials in humans have
      resulted in conflicting findings. Both the human and animal study results may be
      attributed to contrasting doses of CLA, isomers, the coexistence of other dietary
      fatty acids, length of study, and inter-and/or intra-species diversities. Recent
      research advances have suggested the importance of CLA isomers in modulating gene
      expression involved in oxidative damage, fatty acid metabolism,
      immune/inflammatory responses, and ultimately atherosclerosis. Although the
      possible mechanisms of action of CLA have been suggested, they have yet to be
      determined.

PMID- 18718023
TI  - Impact of BRAF, MLH1 on the incidence of microsatellite instability high
      colorectal cancer in populations based study.
AB  - We have identified an alternative pathway of tumorigenesis in sporadic colon
      cancer, involving microsatellite instability due to mismatched repair
      methylation, which may be driven by mutations in the BRAF gene (V600E).
      Colorectal cancer (CRC) is the most common cancer in the world, and African
      Americans show a higher incidence than other populations in the United States. We
      analyzed sporadic CRCs in Omani (of African origin, N = 61), Iranian (of
      Caucasian origin, N = 53) and African American (N = 95) patients for
      microsatellite instability, expression status of mismatched repair genes (hMLH1,
      hMSH2) and presence of the BRAF (V600E) mutation. In the Omani group, all tumors
      with BRAF mutations were located in the left side of the colon, and for African
      Americans, 88% 7 of tumors with BRAF mutations were found in the right side of
      the colon. In African Americans, 31% of tumors displayed microsatellite
      instability at two or more markers (MSI-H), while this rate was 26% and 13% for
      tumors in the Iranian and Omani groups, respectively. A majority of these MSI-H
      tumors were located in the proximal colon (right side) in African American and
      Iranian subjects, whereas most were located in the distal colon (left side) in
      Omani subjects. Defects in hMLH1 gene expression were found in 77% of MSI-H
      tumors in both African Americans and Iranians and in 38% of tumors in Omanis.
      BRAF mutations were observed in all subjects: 10% of tumors in African Americans
      (8/82), 2% of tumors in Iranians (1/53), and 19% of tumors in Omanis (11/59). Our
      findings suggest that CRC occurs at a younger age in Omani and Iranian patients,
      and these groups showed a lower occurrence of MSI-H than did African American
      patients. Our multivariate model suggests an important and significant role of
      hMLH1 expression and BRAF mutation in MSI-H CRC in these populations. The high
      occurrence of MSI-H tumors in African Americans may have significant implications
      for treatment, since patients with MSI-H lesions display a different response to
      chemotherapeutic agents such as 5-fluorouracil.

PMID- 18718024
TI  - Chinese herb related molecules of cancer-cell-apoptosis: a minireview of progress
      between Kanglaite injection and related genes.
AB  - Many kinds of Chinese herb had been confirmed to have the character of anti
      tumor, clinical reports about anti-tumor effects of Chinese herb had also been
      found in recent years, but most of the reports were focused on the clinical
      treatment of effectiveness for Chinese herb, on the other hand, review about
      Chinese herbal related with molecules on cancer-cell-apoptosis was seldom, many
      scientists could not believe such kinds of clinical describes about anti-tumor
      effects for Chinese herb, because these describes were lack of molecular biology
      evidence. Kanglaite(KLT) injection is an anti-tumor new drug which extracts from
      Chinese medicine-coix seed with modern advanced pharmaceutical technology, it is
      also a new biphase extended-spectrum anticancer medicine, the food and drug
      administration(FDA) of United States also approved a phase II trial of KLT to
      test its efficacy in treating non-small-cell lung cancer. Some studies show it
      could inhibit some anti-apoptotic gene and activate some pro-apoptotic gene, its
      injection solution is one of the new anticancer medicine that can significantly
      inhibit a various kinds of tumor cells, so it has become the core of research
      that how to further explore KLT injection to promote tumor cell apoptosis by
      impacting on related genes. In this review, the relationship between KLT and some
      tumor cell apoptosis molecules had been discussed and reviewed generally.

PMID- 18718025
TI  - Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in
      ventilator-induced lung injury.
AB  - INTRODUCTION: Poly (ADP-ribose) polymerase (PARP) participates in inflammation by
      cellular necrosis and the nuclear factor-kappa-B (NF-kappaB)-dependent
      transcription. The purpose of this study was to examine the roles of PARP in
      ventilator-induced lung injury (VILI) in normal mice lung. METHODS: Male C57BL/6
      mice were divided into four groups: sham tracheostomized (sham), lung-protective
      ventilation (LPV), VILI, and VILI with PARP inhibitor PJ34 pretreatment
      (PJ34+VILI) groups. Mechanical ventilation (MV) settings were peak inspiratory
      pressure (PIP) 15 cm H2O + positive end-expiratory pressure (PEEP) 3 cm H2O + 90
      breaths per minute for the LPV group and PIP 40 cm H2O + PEEP 0 cm H2O + 90
      breaths per minute for the VILI and PJ34+VILI groups. After 2 hours of MV, acute
      lung injury (ALI) score, wet-to-dry (W/D) weight ratio, PARP activity, and
      dynamic compliance (CD) were recorded. Tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NOX)
      in the bronchoalveolar lavage fluid and NF-kappaB DNA-binding activity in tissue
      homogenates were measured. RESULTS: The VILI group showed higher ALI score, W/D
      weight ratio, MPO activity, NOX, and concentrations of TNF-alpha and IL-6 along
      with lower CD than the sham and LPV groups (P < 0.05). In the PJ34+VILI group,
      PJ34 pretreatment improved all histopathologic ALI, inflammatory profiles, and
      pulmonary dynamics (P < 0.05). NF-kappaB activity was increased in the VILI group
      as compared with the sham and LPV groups (P < 0.05) and was decreased in the
      PJ34+VILI group as compared with the VILI group (P = 0.009). Changes in all
      parameters were closely correlated with the PARP activity (P < 0.05). CONCLUSION:
      Overactivation of PARP plays an important role in the inflammatory and
      transcriptional pathogenesis of VILI, and PARP inhibition has potentially
      beneficial effects on the prevention and treatment of VILI.

PMID- 18718026
TI  - The costs of traumatic brain injury due to motorcycle accidents in Hanoi,
      Vietnam.
AB  - BACKGROUND: Road traffic accidents are the leading cause of fatal and non-fatal
      injuries in Vietnam. The purpose of this study is to estimate the costs, in the
      first year post-injury, of non-fatal traumatic brain injury (TBI) in motorcycle
      users not wearing helmets in Hanoi, Vietnam. The costs are calculated from the
      perspective of the injured patients and their families, and include
      quantification of direct, indirect and intangible costs, using years lost due to
      disability as a proxy. METHODS: The study was a retrospective cross-sectional
      study. Data on treatment and rehabilitation costs, employment and support were
      obtained from patients and their families using a structured questionnaire and
      The European Quality of Life instrument (EQ6D). RESULTS: Thirty-five patients and
      their families were interviewed. On average, patients with severe, moderate and
      minor TBI incurred direct costs at USD 2,365, USD 1,390 and USD 849, with time
      lost for normal activities averaging 54 weeks, 26 weeks and 17 weeks and years
      lived with disability (YLD) of 0.46, 0.25 and 0.15 year, respectively.
      CONCLUSION: All three component costs of TBI were high; the direct cost accounted
      for the largest proportion, with costs rising with the severity of TBI. The
      results suggest that the burden of TBI can be catastrophic for families because
      of high direct costs, significant time off work for patients and caregivers, and
      impact on health-related quality of life. Further research is warranted to
      explore the actual social and economic benefits of mandatory helmet use.

PMID- 18718027
TI  - Some peace of mind: assessing a pilot intervention to promote mental health among
      widows of injecting drug users in north-east India.
AB  - BACKGROUND: HIV prevalence in north-east India is high and injecting drug use
      (IDU) is common. Due to HIV-related deaths there are increasing numbers of IDU
      widows, many of whom are HIV infected, and experiencing poor health, social
      isolation, discrimination and poverty, all factors likely to be compromising
      their mental health. There is increasing recognition of the links between HIV and
      mental health. METHODS: The aim of this study was to pilot a peer-facilitated,
      participatory action group (PAG) process and assess the impact of the
      intervention on the mental health of participants. The intervention consisted of
      10 PAG meetings involving 74 IDU widows. Changes in quality of life (WHOQOL
      BREF), mental health (GHQ12) and somatic symptoms were assessed. The value of the
      intervention from the perspective of the participants was captured using a
      qualitative evaluation method (Most Significant Change). RESULTS: Participants'
      quality of life, mental health and experience of somatic symptoms improved
      significantly over the course of the intervention, and the women told stories
      reflecting a range of 'significant changes'. CONCLUSION: This pilot intervention
      study demonstrated that a participatory approach to mental health promotion can
      have a positive impact on the lives of vulnerable women, and the potential to
      contribute to HIV prevention. Further investigation is warranted.

PMID- 18718028
TI  - Improving community health worker use of malaria rapid diagnostic tests in
      Zambia: package instructions, job aid and job aid-plus-training.
AB  - BACKGROUND: Introduction of artemisinin combination therapy (ACT) has boosted
      interest in parasite-based malaria diagnosis, leading to increased use of rapid
      diagnostic tests (RDTs), particularly in rural settings where microscopy is
      limited. With donor support, national malaria control programmes are now
      procuring large quantities of RDTs. The scarcity of health facilities and trained
      personnel in many sub-Saharan African countries means that limiting RDT use to
      such facilities would exclude a significant proportion of febrile cases. RDT use
      by volunteer community health workers (CHWs) is one alternative, but most sub
      Saharan African countries prohibit CHWs from handling blood, and little is known
      about CHW ability to use RDTs safely and effectively. This Zambia-based study was
      designed to determine: (i) whether Zambian CHWs could prepare and interpret RDTs
      accurately and safely using manufacturer's instructions alone; (ii) whether
      simple, mostly pictorial instructions (a "job aid") could raise performance to
      adequate levels; and (iii) whether a brief training programme would produce
      further improvement. METHODS: The job aid and training programme were based on
      formative research with 32 CHWs in Luangwa District. The study team then
      recruited three groups of CHWs in Chongwe and Chibombo districts. All had
      experience treating malaria based on clinical diagnosis, but only six had prior
      RDT experience. Trained observers used structured observation checklists to score
      each participant's preparation of three RDTs. Each also read 10 photographs
      showing different test results. The first group (n = 32) was guided only by
      manufacturer's instructions. The second (n = 21) used only the job aid. The last
      (n = 26) used the job aid after receiving a three-hour training. RESULTS: Mean
      scores, adjusted for education, age, gender and experience, were 57% of 16 RDT
      steps correctly completed for group 1, 80% for group 2, and 92% for group 3. Mean
      percentage of test results interpreted correctly were 54% (group 1), 80% (group
      2), and 93% (group 3). All differences were statistically significant (p < 0.05).
      CONCLUSION: Manufacturer's instructions like those provided with the RDTs used in
      this study are insufficient to ensure safe and accurate use by CHWs. However,
      well-designed instructions plus training can ensure high performance. More study
      is underway to determine how well this performance holds up over time.

PMID- 18718029
TI  - Unusually stable abnormal karyotype in a highly aggressive melanoma negative for
      telomerase activity.
AB  - Malignant melanomas are characterized by increased karyotypic complexity,
      extended aneuploidy and heteroploidy. We report a melanoma metastasis to the
      peritoneal cavity with an exceptionally stable, abnormal pseudodiploid karyotype
      as verified by G-Banding, subtelomeric, centromeric and quantitative Fluorescence
      in Situ Hybridization (FISH). Interestingly this tumor had no detectable
      telomerase activity as indicated by the Telomere Repeat Amplification Protocol.
      Telomeric Flow-FISH and quantitative telomeric FISH on mitotic preparations
      showed that malignant cells had relatively short telomeres. Microsatellite
      instability was ruled out by the allelic pattern of two major mononucleotide
      repeats. Our data suggest that a combination of melanoma specific genomic
      imbalances were sufficient and enough for this fatal tumor progression, that was
      not accompanied by genomic instability, telomerase activity, or the engagement of
      the alternative recombinatorial telomere lengthening pathway.

PMID- 18718030
TI  - The dynamic evolutionary history of the bananaquit (Coereba flaveola) in the
      Caribbean revealed by a multigene analysis.
AB  - BACKGROUND: The bananaquit (Coereba flaveola) is a small nectivorous and
      frugivorous emberizine bird (order Passeriformes) that is an abundant resident
      throughout the Caribbean region. We used multi-gene analyses to investigate the
      evolutionary history of this species throughout its distribution in the West
      Indies and in South and Middle America. We sequenced six mitochondrial genes
      (3744 base pairs) and three nuclear genes (2049 base pairs) for forty-four
      bananaquits and three outgroup species. We infer the ancestral area of the
      present-day bananaquit populations, report on the species' phylogenetic,
      biogeographic and evolutionary history, and propose scenarios for its
      diversification and range expansion. RESULTS: Phylogenetic concordance between
      mitochondrial and nuclear genes at the base of the bananaquit phylogeny supported
      a West Indian origin for continental populations. Multi-gene analysis showing
      genetic remnants of successive colonization events in the Lesser Antilles
      reinforced earlier research demonstrating that bananaquits alternate periods of
      invasiveness and colonization with biogeographic quiescence. Although nuclear
      genes provided insufficient information at the tips of the tree to further
      evaluate relationships of closely allied but strongly supported mitochondrial DNA
      clades, the discrepancy between mitochondrial and nuclear data in the population
      of Dominican Republic suggested that the mitochondrial genome was recently
      acquired by introgression from Jamaica. CONCLUSION: This study represents one of
      the most complete phylogeographic analyses of its kind and reveals three patterns
      that are not commonly appreciated in birds: (1) island to mainland colonization,
      (2) multiple expansion phases, and (3) mitochondrial genome replacement. The
      detail revealed by this analysis will guide evolutionary analyses of populations
      in archipelagos such as the West Indies, which include islands varying in size,
      age, and geological history. Our results suggest that multi-gene phylogenies will
      permit improved comparative analysis of the evolutionary histories of different
      lineages in the same geographical setting, which provide replicated "natural
      experiments" for testing evolutionary hypotheses.

PMID- 18718032
TI  - New long-term oxygen therapy technology: the transition continues.

PMID- 18718031
TI  - Raised intrathecal levels of APRIL and BAFF in patients with systemic lupus
      erythematosus: relationship to neuropsychiatric symptoms.
AB  - INTRODUCTION: The tumour necrosis factor (TNF) family ligands BAFF (B-cell
      activating factor of TNF family) and APRIL (a proliferation-inducing ligand) are
      essential for B-cell survival and function. Elevated serum levels of BAFF and
      APRIL have been reported earlier in patients with systemic lupus erythematosus
      (SLE). Since autoantibody formation in the central nervous system (CNS) is a
      distinct feature of neuropsychiatric SLE (NPSLE), we have investigated whether
      NPSLE is associated with an enhanced intrathecal production of APRIL and BAFF.
      METHODS: Levels of BAFF and APRIL in cerebrospinal fluid (CSF) and serum from
      healthy controls, SLE patients without CNS involvement, and patients with NPSLE
      were determined by enzyme-linked immunosorbent assay. Interleukin-6 (IL-6) levels
      were determined by an IL-6-specific bioassay. RESULTS: SLE patients had levels of
      APRIL in CSF that were more than 20-fold higher and levels of BAFF in CSF that
      were more than 200-fold higher than those of healthy controls. Separate analyses
      of SLE patients with and without CNS involvement revealed that NPSLE patients had
      enhanced levels of APRIL in CSF. BAFF and APRIL were likely produced locally in
      the CNS as CSF and serum levels did not correlate. Moreover, CSF levels of APRIL
      correlated with BAFF but not with IL-6, suggesting that APRIL and BAFF in the CNS
      are regulated together but that they are produced independently of IL-6.
      CONCLUSION: To our knowledge this is the first study to show elevated levels of
      BAFF and APRIL in CSF of SLE patients. APRIL was augmented in NPSLE patients
      compared with SLE patients without CNS involvement. APRIL and BAFF antagonists
      breeching the blood-brain barrier therefore could have beneficial effects on SLE
      patients, in particular patients with NPSLE.

PMID- 18718033
TI  - New guideline on treating tobacco use and dependence: 2008 update is an
      opportunity to advance.

PMID- 18718035
TI  - The 23rd annual New Horizons Symposium. Pulmonary rehabilitation: the expanding
      evidence base. Foreword.

PMID- 18718036
TI  - Mechanisms of functional loss in patients with chronic lung disease.
AB  - Functional loss (often quantified as exercise limitation) is common in patients
      with chronic lung disease. The factors involved are multiple and many may be
      present together in a given patient. Ventilatory factors involve an imbalance in
      load/capacity relationships. Specifically, breathing loads from abnormal
      respiratory-system mechanics and/or excessive ventilatory demand cannot be
      handled by respiratory muscles that are dysfunctional or malpositioned. Gas
      exchange factors involve impaired ventilation-perfusion relationships that lead
      to hypoxemia, impaired oxygen delivery, and pulmonary hypertension.
      Cardiovascular factors involve coexisting intrinsic heart disease, right
      ventricular overload from pulmonary vascular abnormalities, and simple
      deconditioning. Skeletal muscle (both respiratory and limb) factors involve
      direct inflammatory mediator effects on muscle function, malnutrition, blood-gas
      abnormalities, compromised oxygen delivery from right-heart dysfunction,
      electrolyte imbalances, drugs, and comorbid states. Other less well understood
      factors include excessive dyspnea, impaired motivation, orthopedic issues, and
      psychiatric issues.

PMID- 18718034
TI  - A comparison of health-care costs in patients with chronic obstructive pulmonary
      disease using lightweight portable oxygen systems versus traditional compressed
      oxygen systems.
AB  - BACKGROUND: Lightweight portable oxygen systems are commonly preferred by
      patients over compressed-oxygen systems that use E-size cylinders. However, cost
      is often perceived as a barrier to the prescription of lightweight portable
      oxygen systems. OBJECTIVE: To compare the overall health-care costs of patients
      with COPD who used lightweight portable oxygen systems to those who used E
      cylinder systems. METHODS: All the patients who used either a lightweight
      portable oxygen system, an E-cylinder system, or an E-cylinder system, then a
      lightweight portable oxygen system, for at least 12 months during the study
      period (January 1, 1999, to December 30, 2004) were identified from the
      administrative database of our regional managed-care system. All direct medical
      utilization and costs were captured for at least the first 12 months that
      supplemental oxygen was dispensed. Other clinical factors that affect costs
      (including age, sex, ethnicity, and comorbidities) were examined and adjusted
      for. RESULTS: Of the 2,725 patients who met the inclusion criteria, 203 used only
      a lightweight portable oxygen system, 2,268 used only an E-cylinder system, and
      254 switched from an E-cylinder system to a lightweight portable oxygen system.
      Among the patients who used only the lightweight portable oxygen system, the
      median total medical costs in the first year were nonsignificantly lower than
      those who used an E-cylinder system ($6,515/y vs $9,503/y). The cost difference
      remained nonsignificant after adjustment for clinical factors. Among the patients
      who switched from one system to the other in the first year, mean monthly health
      care costs while using the lightweight portable oxygen system ($1,428) were not
      significantly different than when using the E-cylinder system ($1,396).
      CONCLUSIONS: The type of oxygen system used did not significantly affect overall
      cost of care in patients with COPD on long-term oxygen therapy.

PMID- 18718037
TI  - A brief history of pulmonary rehabilitation.
AB  - Pulmonary rehabilitation is widely accepted as effective therapy for patients
      with chronic obstructive pulmonary disease (COPD). This paper presents a brief
      (and somewhat subjective) history of pulmonary rehabilitation, and stresses the
      development of the exercise component. Until the middle of the 20th century,
      patients with COPD were advised to avoid the dyspnea that activity brings. Barach
      can be credited with positing that patients with COPD should strive to be more
      active. In the 1960s Petty created the multi-disciplinary team that was found to
      be effective in delivering pulmonary rehabilitation. In the 1980s doubts surfaced
      as to the ability of rehabilitative exercise to improve muscle function in COPD,
      but in the 1990s studies showed that well-designed exercise programs caused
      beneficial physiologic adaptations. The current decade has yielded studies that
      exploited those insights to design interventions that boost the effectiveness of
      rehabilitative exercise.

PMID- 18718038
TI  - The roles of bronchodilators, supplemental oxygen, and ventilatory assistance in
      the pulmonary rehabilitation of patients with chronic obstructive pulmonary
      disease.
AB  - In patients with chronic obstructive pulmonary disease, pulmonary rehabilitation
      significantly improves dyspnea, exercise capacity, quality of life, and health
      resource utilization. These benefits result from a combination of education
      (especially in the promotion of collaborative self-management strategies and
      physical activity), exercise training, and psychosocial support. Exercise
      training increases exercise capacity and reduces dyspnea. Positive outcomes from
      exercise training may be enhanced by 3 interventions that permit the patient to
      exercise train at a higher intensity: bronchodilators, supplemental oxygen (even
      for the nonhypoxemic patient), and noninvasive ventilatory support.

PMID- 18718039
TI  - Pulmonary rehabilitation for patients who undergo lung-volume-reduction surgery
      or lung transplantation.
AB  - Patients preparing for or recovering from lung-volume-reduction surgery (LVRS) or
      lung transplantation represent a selected group of patients with advanced chronic
      respiratory disease. Such patients typically have severe ventilatory limitation
      and disability and are at high risk of preoperative and postoperative
      complications. Pulmonary rehabilitation is an ideal setting in which to: address
      the patient's questions and knowledge-deficits regarding his or her disease and
      its treatment; ensure that the patient understands the nature, potential
      benefits, risks, and expected outcomes of the surgery relative to medical
      therapies, and; prepare physically and emotionally for the surgery. Pulmonary
      rehabilitation also may improve survival to and/or outcomes of LVRS and
      transplantation, at least in part by stabilizing and improving the patient's
      exercise tolerance and muscle function. Further work is needed to determine
      whether pulmonary rehabilitation can augment the benefits and outcomes of LVRS or
      lung transplantation, reduce postoperative complications, or improve patient
      survival to or following the surgery.

PMID- 18718040
TI  - Pulmonary rehabilitation: summary of an evidence-based guideline.
AB  - Pulmonary rehabilitation has emerged as a standard of care for patients with
      chronic lung disease, based on a growing body of scientific evidence. Over recent
      decades, several organizations have championed pulmonary rehabilitation and
      developed comprehensive statements, practice guidelines, and evidence-based
      guidelines. Documenting the scientific evidence underlying clinical practice has
      been important in overcoming skepticism and convincing health professionals,
      health-care institutions, third-party payers, and regulatory agencies to support
      pulmonary rehabilitation programs. The literature on pulmonary rehabilitation has
      increased substantially and provided justification for including pulmonary
      rehabilitation in practice guidelines for chronic obstructive pulmonary disease
      and other chronic lung diseases. Therefore, the American College of Chest
      Physicians and the American Association of Cardiovascular and Pulmonary
      Rehabilitation decided to update their 1997 guidelines with a systematic,
      evidence-based review of the literature since the previous review. The panel
      updated prior topics and recommendations and reviewed new topics. Recommendations
      were given for outcomes of comprehensive pulmonary rehabilitation programs,
      including lower-extremity exercise training, dyspnea, health-related quality of
      life, health-care utilization, survival, psychosocial outcomes, and long-term
      benefits. Additional topics include the duration of pulmonary rehabilitation,
      post-rehabilitation maintenance strategies, intensity of aerobic exercise
      training, strength training, anabolic drugs, upper-extremity training,
      inspiratory-muscle training, education, psychological and behavioral components,
      oxygen supplementation, noninvasive ventilation, nutrition supplementation,
      rehabilitation for patients with disorders other than chronic obstructive
      pulmonary disease, and future pulmonary rehabilitation research. These guidelines
      provide an excellent summary of the recent literature and further strengthen the
      scientific basis of pulmonary rehabilitation.

PMID- 18718041
TI  - Neuropsychiatric function in chronic lung disease: the role of pulmonary
      rehabilitation.
AB  - Chronic lung disease is associated with increased psychological distress
      (especially anxiety and depression) and neuropsychological impairments (primarily
      in flexible problem-solving and information-sequencing), which decrease quality
      of life, disease management, and survival. This review summarizes current data
      regarding the prevalence of neuropsychiatric disorders, the assessment tools
      commonly used to measure and monitor neuropsychiatric symptoms, the effect of
      pulmonary rehabilitation on neuropsychiatric symptoms, the mechanisms by which
      exercise rehabilitation may influence neuropsychiatric functioning, and the
      clinical implications of the data.

PMID- 18718042
TI  - A case of rapidly progressive necrotizing pneumonia caused by community-acquired
      methicillin-resistant Staphylococcus aureus.
AB  - We present the case of a patient with a necrotizing multilobar pneumonia caused
      by community-acquired methicillin-resistant Staphylococcus aureus (MRSA). The
      patient presented with shortness of breath and a productive cough of 3 days
      duration. On arrival to the emergency department she was intubated for increased
      work of breathing and given vasopressors for hypotension refractory to fluid
      resuscitation. Blood cultures taken at admission, sputum cultures from the
      patient's endotracheal tube, and bronchoalveolar lavage cultures all grew S.
      aureus resistant to penicillinase-resistant penicillins. Over the following days
      the patient's respiratory function deteriorated as she grew progressively
      hypoxemic and hypercarbic despite aggressive mechanical ventilation and
      intravenous antibiotics. On day 4 of her hospitalization a computed tomogram
      revealed extensive pulmonary necrosis consistent with necrotizing pneumonia. The
      patient's family elected to withdraw support, and the patient rapidly died
      following cessation of mechanical ventilation.

PMID- 18718043
TI  - Lymphomatoid granulomatosis: a rare cause of multiple pulmonary nodules.

PMID- 18718044
TI  - Nonasthmatic eosinophilic bronchitis mimics asthma.

PMID- 18718045
TI  - Reduced growth and integrin expression of prostate cells cultured with lycopene,
      vitamin E and fish oil in vitro.
AB  - Integrins are transmembrane proteins that facilitate the interaction of cells
      with the extracellular environment. They have also been implicated in cancer
      progression. The effects of nutrients thought to be involved in the prevention of
      prostate cancer on integrin expression have not been determined. Prostate cancer
      cell lines representing a range of malignancy from normal (RWPE-1) to highly
      invasive phenotypes (22Rv1 < LNCaP < PC-3) were cultured with or without lycopene
      (10 nM), vitamin E (5 microm) or fish oil (100 microm) for 48 h. Growth and
      integrin (alpha2beta1, alphavbeta3 and alphavbeta5) expression were assessed
      using Trypan Blue exclusion and monoclonal antibodies combined with flow
      cytometry. Vitamin E enhanced (P < 0.001) whereas fish oil reduced the growth of
      all the cell lines tested (P < 0.001). Lycopene had no effect on growth. All the
      malignant cell lines exhibited lower expression of alpha2beta1 with the addition
      of lycopene to culture media. Supplemental fish oil reduced alpha2beta1 in most
      invasive cell lines (LNCaP and PC-3). Each nutrient at physiological levels
      reduced integrins alphavbeta3 and alphavbeta5 in most invasive cell lines (PC-3).
      The results suggest that integrins may represent an additional target of
      bioactive nutrients and that the effects of nutrients may be dependent on the
      type of cell line used.

PMID- 18718046
TI  - Anomalous aortic origin of the left coronary artery.

PMID- 18718047
TI  - [Effect of shRNA targeted to beta-catenin on K562 cell growth].
AB  - In order to investigate the effect of shRNA targeted to beta-catenin on the
      growth of K562 cells, plasmid containing beta-catenin specific shRNA sequence was
      transfected into K562 cells by lipofectamine 2000, and G418 was added to screen
      the positive cells. Real-time PCR and Western blot were used to detect the
      expression of beta-catenin. Cell growth curve, MTT and colony forming cell assays
      were used to evaluate the proliferation potential of cells. The results showed
      that the mRNA level of beta-catenin was reduced significantly in K562 cells
      transfected into interfering plasmid as compared with control plasmid, while the
      protein level failed to demonstrate difference by the time of 72 hours after
      transfection. After long-term culture with G418, the count of positive cells
      enhanced in control group while no positive cells survived in the interfering
      group. Colony-forming cell assays revealed that the K562 cells in interfering
      group formed colonies with very small size and low forming rate, compared with
      the control group, though the growth curve and MTT failed to illustrate
      differences. It is concluded that the beta-catenin-specific shRNA mediated by
      plasmid can effectively knockdown the expression of beta-catenin gene and inhibit
      the colony-forming ability in K562 cells, it is a potential target for the
      therapy of CML, even in blast crisis.

PMID- 18718048
TI  - [SphK-1/S1P signal pathway in CML cells].
AB  - Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of
      transformed hematopoietic progenitor cells. In order to investigate the role of
      sphingosine kinase-1 (SphK-1)/sphingosine 1-phosphate (S1P) signal pathway in the
      expression of CML cells, and to explore whether P210(bcr/abl) involved is
      activating SphK-1/S1P signal pathwey, the expressions of SphK-1 and S1P receptor
      mRNA in bcr/abl positive K562 cells and bcr/abl positive primary CML cells were
      detected by RT-PCR, the imatinib mesylate, the specific inhibitor of
      P210(bcr/abl) was employed to inhibit the P210(bcr/abl) tyrosine kinases of K562
      cells and CML primary cells, and then the intracellular SphK-1 activity was
      assayed. The results indicated that after being cultured with 2.5 micromol/L
      imatinib mesylate for 0.5, 2, 6, 24 and 48 hours, the intensions of inhibiting
      SphK-1 activity were 0.007%, 38.9%, 34.6%, 28.1% and 76.1% resepectively. SphK-1
      activity in CML cells also was reduced by 2.5 micromol/L imatinib mesylate (16.8%
      - 41.9% decrease). It is concluded that the CML cells express SphK-1 and
      different S1P receptor, and P210(bcr/abl) fusion protein in CML cells can
      activate SphK-1.

PMID- 18718049
TI  - [Expression of a tumor related gene chp2 in leukemia cells].
AB  - The purpose of this study was to investigate the expression feature of a human
      tumor related gene chp2 in leukemia primary cells and leukemia cell lines, real
      time quantitative PCR (RQ-PCR) was performed to detect the expression level of
      chp2 gene in peripheral blood mononuclear cells from 10 healthy individuals (as
      control) and 24 cases of leukemia, and in 4 kinds of leukemia cell lines. The
      results showed that the detection rate of chp2 gene in 10 normal controls was
      80%, positive expression was (0.744 +/- 0.682) x 10(5) cps/microl. The expression
      levels of chp2 mRNA leukemia primary cells and leukemia cell lines were
      significantly higher than that in the normal control (p < 0.05). The expression
      levels of chp2 mRNA were higher in AML cells (7 cases), CML cells (6 cases), ALL
      cells (7 cases) and CLL cells (4 cases), and their expression levels were (11.637
      +/- 5.588), (6.122 +/- 3.785), (4.262 +/- 2.561) and (3.434 +/- 1.974) x 10(5)
      cps/microl respectively. Gene chp2 positively expressed in four kinds of leukemia
      cell lines, and the expression levels in K562 cells, Jurkat cells, HL-60 cells
      and M07e cells were (5.243 +/- 1.852), (4.463 +/- 1.621), (4.137 +/- 1.837) and
      (2.578 +/- 1.137) x 10(6) cps/microl respectively. The expression level in
      leukemia cell lines was higher than that in primary cells. It is concluded that
      the human tumor related gene chp2 expression in leukemia primary cells and
      leukemia cell lines significantly increase, which may play an important role in
      growth process of leukemia cells.

PMID- 18718050
TI  - [Expression of a tumor related gene fgfr3 mRNA in leukemic cells and its clinical
      significance].
AB  - This study was aimed to explore fgfr3 gene expression in leukemic cells and its
      clinical significance. The expression levels of fgfr3 mRNA in 4 leukemic cell
      lines and bone marrow samples from 96 patients with leukemia and 14 controls were
      assayed by RT-PCR. 96 patients with leukemia included 36 cases of acute myeloid
      leukemia (AML), 29 cases of acute lymphoblastic leukemia (ALL), 31 cases of
      chronic myelogenous leukemia (CML). The results indicated that fgfr3 gene could
      be detected in both K562 and U937 cell lines, but not in HL-60 and SHI-1 cell
      lines. The positive expression rates of fgfr3 mRNA in AL and CML were 46.15% and
      51.61% respectively, and were higher than that in control (14.29%, p < 0.05). The
      positive expression rates of fgfr3 mRNA in AML and ALL were 44.44% and 48.28%
      respectively, and were higher than that in control (p < 0.05). The increased
      level of fgfr3 mRNA had a positive correlation with high white blood cell count
      of > or = 20 x 10(9)/L (p < 0.05). Higher fgfr3 mRNA expression positively
      correlated with fuse genes of bcr/abl in ALL (r = 0.151, p < 0.05). The
      expression of fgfr3 gene in AL was not related with chromosome abnormality. In
      conclusion, the over expression of fgfr3 gene exists in AL and CML patients, it
      suggests that fgfr3 gene may be partially involved in leukemogenesis.

PMID- 18718051
TI  - [Gene expression profile of human TGF-beta signal transduction pathway of B cell
      type acute lymphocytic leukemia].
AB  - This study was aimed to investigate the gene expression profile of TGF-beta
      signal transduction pathway in B-cell type acute lymphocytic leukemia (B-ALL).
      The gene expression profiles in B-ALL primary cells and cell lines (NALM6 cells,
      Raji cells), B-lymphocyte of control were detected by cDNA microarray including
      113 different genes in human TGF-beta/BMP signal transduction pathway, and TGF
      beta(1) mRNA expression was detected by real time RT-PCR. The B lymphocytes in
      peripheral blood of heacthy persons sorted by flow cytometry were used as
      control. The difference between them was compared. The results showed that as
      compared with B lymphocytes in peripheral blood of heacthy persons, the TGF
      beta(1) expression in B-ALL cells, NALM6 cells and Raji cells were down
      regulationed, myc and smad1 gene expressions were up-regulated, IL-6, smad 7 gene
      expressions were down-regulated. It is concluded that TGF-beta signal
      transduction is abnormal in B-cell type acute lymphocytic leukemia.

PMID- 18718052
TI  - [Differential expression levels of killer immunoglobin-like receptor genotype in
      patients with hematological malignancies between high-risk and standard-risk
      groups].
AB  - This study was purposed to investigate the killer immunoglobulin-like receptor
      (KIR) genotype in patients with hematological malignancies. The sequence specific
      primer-polymerase chain reaction (PCR-SSP) technique was performed for the
      amplification of six inhibitory KIR genes (KIR2DL1-2DL4, 3DL1-3DL2) and six
      activating KIR genes (KIR2DS1-S5, 3DS1). The methods of KIR-SSP was used to
      determine the KIR genotypes of 54 leukemia patients, including 14 patients with
      acute myeloid leukemia (AML), 16 with acute lymphoblastic leukemia (ALL), 20 with
      chronic myeloid leukemia (CML), 3 with myelodysplastic syndrome (MDS) and 1 with
      acute myeloid-lymphoblast leukemia (AMLL). 54 patients were classified as high
      risk group (n = 27) and standard risk group (n = 27). The expression of KIR in NK
      cells and T cells was detected by flow cytometry. The frequencies of activating
      KIR genes in standard risk group were higher than those in high risk group,
      especially 2DS1 (p = 0.014), or 2DS2 (p = 0.046), or 3DS1 (p = 0.027). However,
      the frequencies of inhibitory KIR genes in standard risk group were similar to
      those in high risk group (p > 0.05). The frequencies of activating KIR genes were
      also higher in standard risk patients with acute AML, as compared with those in
      high risk patients with acute AML, particularly 2DS1 (66.7% vs 29.4%, p = 0.022),
      2DS2 (57.6% vs 17.6%, p = 0.013), and 2DS3 (33.3% vs 5.9%, p = 0.039). The
      percentages of patients in high-risk group who expressed more than two kinds of
      activating KIRs were lower that those in standard-risk group (p = 0.035). There
      was no difference in the expressions of CD158a, CD158b, and CD158e on NK cells
      and T cells between high-risk group and standard-risk group (p > 0.05). In
      conclusions, different expressions of activating KIR genes were found in patients
      between high-risk group and standard-risk group.

PMID- 18718053
TI  - [Establishment of the methods to detect nucleophosmin gene and its mutation in
      acute myelogenous leukemia].
AB  - This study was aimed to establish the PCR methods to detect nucleophosmin (NPM)
      gene and its mutation. 2 leukemia cell lines and 23 specimens from patients with
      acute myelogenous leukemia (AML) were investigated. The level of NPM mRNA was
      detected by RT-PCR. The exon-12 of NPM gene in leukemia cell lines was amplified
      by PCR and sequenced. Using the plasmid containing cDNA of NPM mutation A as a
      positive template, the PCR procedure to detect mutation A was established and
      evaluated. Then, the mutation of NPM was analyzed in 23 AML specimens. The
      results indicated that the expression level of NPM in leukemia cell lines was
      higher than that in normal cells. Different overexpression levels of NPM mRNA
      were found in all 23 AML specimens. PCR indicated that mutation had been not
      occurred at NPM exon-12 in THP1 and K562 cells, but a T base was deleted at 3'
      untranslated region of NPM gene in K562 cells. The PCR used for directly
      detecting NPM mutation A can specially amplify the NPM mutation gene. The method
      was reproducible, whose coefficient of variability was 1.6% and 3.1% in intra-and
      inter-assays respectively. The lowest detectable limit was 100 pg cDNA. Using the
      PCR methods, NPM mutation A could be detected in 2 out of 23 AML specimens, but
      NPM mutation A was not found in THP1 and K562 cells. It is concluded that the RT
      PCT method detecting NPM mRNA level and the PCR method detecting directly NPM
      mutation are established. NPM mRNA is overexpressed in leukemia cells; NPM
      mutation A occurs in some AML patients.

PMID- 18718054
TI  - [Expression of integrins in bone marrow mesenchymal stem cells derived from
      patients with chronic myeloid leukemia].
AB  - The purpose of this study was to investigate the growth characteristics and the
      expression level of integrin mRNA of the cultured bone marrow mesenchymal stem
      cells (BMMSCs) from patients with chronic myeloid leukemia (CML) in myeloid
      crisis (MC), and explore the role of BMMSCs in pathogenesis of CML. Five CML
      patients were enrolled in experimental group, five healthy persons were used as
      control. BMMSCs were cultured in vitro. The morphology of BMMSCs was observed
      every day and the growth curve were portrayed, and the ability of cell
      proliferation were detected according to the daily results of cell counting.
      Total RNA was extracted from third and fourth passages of BMMSCs, The expression
      of integrins mRNA of BMMSCs were measured by real-time PCR. The results showed
      that the BMMSCs of experimental and control groups had no difference in growth
      characterisctics, but the expression of integrins mRNA of the BMMSCs was higher
      in CML patients than in normal control group (p < 0.05). It is concluded that the
      abnormally high expression of integrins of BMMSC from the CML patients take part
      in pathogenesis of CML.

PMID- 18718055
TI  - [Relationships of serum selenium, VEGF and sFas levels in leukemia patients].
AB  - In order to investigate the relationships of cancer chemopreventive trace element
      selenium, vascular endothelial growth factor (VEGF) and soluble Fas (sFas) in
      leukemia patients, serum selenium concentration was measured by atomic
      spectrometry and levels of VEGF and sFas were simultaneously detected by enzyme
      linked immunosorbent assay (ELISA). Relationships of selenium, VEGF and sFas were
      analyzed by linear correlation. The results showed that serum selenium
      concentration in newly-diagnosed patients and relapsed patients was significantly
      lower than that in the control group (p < 0.05), especially in relapsed group.
      VEGF and sFas concentrations of refractory/relapsed group were significantly
      higher than those in the control group and the remission group (p < 0.05). But no
      significant difference was found between the remission group and the control
      group (p > 0.05). In leukemia patients, negative correlation was observed between
      selenium and VEGF (r = -0.529, p < 0.01), so did between selenium and sFas (r = 
      0.432, p < 0.01). Positive correlation was found between VEGF and sFas (r =
      0.663, p < 0.01). It is concluded that the selenium, VEGF and sFas may take part
      in the occurrence of MDR in leukemia patients. Selenium has negative correlation
      with VEGF and sFas, which means that it may be used as an effective assistant
      agent to improve therapeutic effect of chemotherapy. However, further study in
      more cases is needed to reach a definite conclusion.

PMID- 18718056
TI  - [Overexpression of CHIP in chronic myeloid leukemia K562 cells induces mitotic
      abnormality].
AB  - This study was aimed to investigate the possible influence of a novel E3
      ubiquitin ligase CHIP (carboxyl terminus of Hsc70/Hsp70-interacting protein) on
      biological characteristics of cancer cells. Stable overexpression models in CML
      K562 cells were established via lipofectamine-mediated wild type CHIP and its TPR
      or U-box deletion mutants gene transfection. Followed G418 pressure selection,
      K562-CHIP stable transfected cell clones were obtained by limited dilution. The
      proliferation status and cell cycle were observed by MTT assay and FACS. The
      expression of related proteins and morphological changes were detected by Western
      blot and Wright-Giemsa staining. The results showed that overexpression of wild
      type CHIP did not inhibit cell proliferation, but slightly increased cell ratio
      of G(2)/M phase. CHIP gene had no effect on the stability of BCR-ABL kinase
      protein. HDAC inhibitor FK228-induced BCR-ABL degradation did not enhanced by
      CHIP. Notably the enlarged cells and abnormal mitotic cells remarkably increased
      in K562 WT-CHIP cells, indicating that CHIP may involve in the regulation of
      mitotic process. It is concluded that wild type CHIP induces mitotic abnormity in
      K562 cells.

PMID- 18718057
TI  - [Effects of chloroquine diphosphate on proliferation and apoptosis of human
      leukemic K562 cells].
AB  - The purpose of this study was to investigate the effects of chloroquine
      diphosphate on the proliferation and apoptosis of human leukemic K562 cells, and
      to elucidate its possible mechanism of activity. The inhibitory effect of
      chloroquine diphosphate with different concentrations on K562 cell proliferation
      was detected by MTT method. Apoptosis was measured by flow cytometry (FCM);
      morphological analysis of apoptosis was performed after staining with propidium
      iodide (PI) under fluorescence microscope; cell apoptosis was assessed by the DNA
      ladder shown agarose gel electrophoresis. After treatment with chloroquine
      diphosphate, K562 cells were stained by Rhodamine 123 to detect changes in
      mitochondrial transmembrane potential (DeltaPsim) by FCM. The results showed that
      the cell viability decreased in dose-dependent manner, following chloroquine
      diphosphate treatment at different concentrations (1.5625, 3.125, 6.25, 12.5, 25,
      50 and 100 micromol/L) for 24, 48 and 72 hours. By FCM analysis, the significant
      increases of sub-G(1) were observed. DNA ladder was detected and apoptotic nuclei
      were observed. DeltaPsim decreased in K562 cells after chloroquine diphosphate
      treatment. It is concluded that the chloroquine diphosphate can inhibit the
      proliferation of K562 cells and induce cell apoptosis, which may relate to down
      regulation of mitochondrial transmembrane potential (DeltaPsim).

PMID- 18718058
TI  - [Regulatory effect of resveratrol on JAK1/STAT3 signal transduction pathway in
      leukemia].
AB  - The aim of this study was to explore the molecule mechanism of resveratrol
      antileukaemia. The mouse lymphocytic leukemia L1210 cells were cultured and the
      expressions of pJAK1 and pSTAT3 protein in L1210 cells were detected by
      immunohistochemistry and immunoprecipitation in vitro. The mouse model with L1210
      leukemia ascites carcinoma was established and activities of singal transduction
      pathway molecules pJAK1 and pSTAT3 were measured by Western blot and
      immunohistochemistry assay in vitro. The results indicated that resveratrol could
      significantly inhibit the JAK1/STAT3 signal transduction pathway, down-regulate
      expressions of pJAK1 and pSTAT3 and reduce the phosphorylation of JAK1 and STAT3
      in a dose-and time-dependent manner. It is concluded that the resveratrol can
      regulate signal transduction pathway and reduce the activation of JAK1/STAT3
      tyrosine phosphorylation significantly, and therefore resveratrol shows
      chemotherapeutic potential to leukaemia.

PMID- 18718059
TI  - [Suppressive effect of artesunate on K562 cell growth and its influence on VEGF
      expression].
AB  - The aim of this study was to investigate the inhibitive effect of artesunate
      (ART) on CML cell line K562 and its influence on VEGF expression in vitro. Human
      CML cell line K562 cells were cultured in RPMI 1640 medium supplemented with 10%
      heat-inactivated fetal calf serum. All cells were cultured in a humidified
      atmosphere of 5% CO2 at 37.0 degrees C. K562 cells in logarithmic growth phase
      were collected and seeded in RPMI-1640 medium, and were treated with ART. At the
      indicated time points, viable cells were counted by trypan blue exclusion method.
      Each assay was triplicated. K562 cells were treated with ART at different
      concentrations. Morphological changes were observed with invert microscope. VEGF
      expression in K562 cells treated with ART at different concentrations and in the
      control group were detected by enzyme-linked immunosorbent assay (ELISA). The
      results indicated that ART obviously induced growth inhibition in K562 cells. The
      relationship between cell inhibition rates and the concentrations of ART showed a
      dose-dependent manner (p < 0.01). VEGF expression of K562 cells treated with ART
      at different concentrations decreased significantly (p < 0.01). No significant
      change of VEGF expression in control group was observed (p > 0.05), while VEGF
      expression was down-regulated significantly in experiment groups (p < 0.01). The
      inhibition rate of K562 cells increased in time and concentration-dependent
      manners. In K562 cell lines treated with ART, VEGF expression was up-regulated at
      first and then down-regulated to a lower level. It is concluded that ART inhibits
      k562 cell proliferation in a dose and time dependent manner. The mechanism
      underlying the inhibitive effect of ART on K562 cells may be realized through
      down-regulation of VEGF expression.

PMID- 18718060
TI  - [Effect of total saponins of Panaxginseng on bax and bcl-xl gene expression in HL
      60 cells].
AB  - The aim of this study was to investigate the effect of the total saponins of
      Panaxginseng (TSPG) on cells expression of apoptosis-related genes bax and bcl-xl
      in HL-60 cells and its mechanism inducing apoptosis of HL-60 cells. The
      morphology of HL-60 cells was observed under normal and fluorescence microscopes;
      the percentage of apoptotic HL-60 cells was assayed by flow cytometry and the DNA
      ladder was observed by DNA agarose gel electrophoresis; the expression changes of
      bax and bcl-xl mRNAs were detected by RT-PCR after HL-60 cells were treated with
      TSPG at final concentrations of 0, 100, 200, 400, 800 and 1600 microg/ml for 48
      hours. The results showed that the percentage of apoptotic HL-60 cells went up as
      the dose increased, the typical apoptotic cell morphology and the appearance of
      apoptotic DNA ladder could be observed when treated with 0 - 400 microg/ml TSPG
      for 48 hours. At the same time and same range of concentration, the expression of
      bax mRNA increased and the bcl-xl expression decreased gradually. When higher
      than 400 microg/ml of TSPG was used, cell necrosis appeared and the percentage of
      apoptotic HL-60 cells even decreased. It is concluded that the apoptosis or
      necrosis in HL-60 cells can be induced by TSPG at certain range of concentration,
      and the percentage of apoptosis is dose-dependent. The effect on up-regulation of
      bax mRNA and down-regulation of bcl-xl mRNA probably play an important role in
      apoptosis of HL-60 cells induced by TSPG.

PMID- 18718061
TI  - [Effects of some traditional Chinese drugs on Mdr1 gene and its expression
      product in K562/A02 cells].
AB  - This study was purposed to investigate the effects of angelicasinensis (Oliv)
      Diel compound injection, vauqueline, ephedrine and strychnine on human
      erythroleukemia multidrug resistance (MDR) K562/A02 cell line Mdr1 gene and p
      glycoprotein. The MTT and trypan blue methods were used to analyze the cytotoxic
      effect of above-mentioned traditional Chinese drug; the expressions of K562/A02
      cells Mdr1 gene and p-glycoprotein were detected by semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR) and Western blot respectively.
      The results showed that after K562/A02 cell were treated with angelicasinensis
      (Oliv) diels compound injection, vauqueline and ephedrine, mRNA transcription of
      Mdr1 gene was reduced significantly (p < 0.01); the expression of P-gp also
      decreased (p < 0.01). The expression level P-gp in group treated with vauqueline
      was the lowest, but the Mdr1 mRNA level and expression of P-gp of K562/A02 cells
      treated with strychnine did not obviously changed. It is concluded that
      angelicasinensis (Oliv) diels compound injection, vauqueline, ephedrine can
      partly reverse the multidrug resistance of K562/A02 cells, the down-regulation of
      Mdr1 gene causing decrease of p-glycoprotein expression may be one of the MDR
      reversal mechanisms in K562/A02 cells.

PMID- 18718062
TI  - [Protection against doxorubicin-induced oxidative damage in normal blood cells by
      naringenin].
AB  - The objective of this study was to investigate the protection by naringenin
      against doxorubicin-induced oxidative damage in normal blood cells. Inhibiting
      effects of naringenin, doxorubicin and naringenin combined with doxorubicind on
      K562 cells and polymorphonuclear leukocytes were detected with MTT method, the
      level of reactive oxygen species (ROS) and lipid peroxidation (MDA), the activity
      of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were examined
      with spectrophotometric method in the K562 cells and polymorphonuclear
      leukocytes. The results indicated that the proliferation of K562 cells was not
      inhibited by the cytotoxicity of doxorubicin in combination of naringenin with
      doxorubicin. As compared with the doxorubicin, the addition of naringenin after
      doxorubicin for 1 hour, the levels of reactive oxygen species (ROS) and lipid
      peroxidation (MDA) obviously decreased, the activity of superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-Px) obviously increased in the
      polymorphonuclear leukocytes, but these were not changed obviously in K562 cells.
      It is concluded naringenin can protect against doxorubicin-induced oxidative
      damage in normal blood cells. The mechanism of naringenin may be elevating
      activities of antioxidant enzyme and degrading oxidative production level in
      normal blood cells, and meanswhile decreasing level of oxidative products.

PMID- 18718063
TI  - [Synergistic effects of arsenic trioxide and proteasome inhibitor bortezomib on
      apoptosis induction in Raji cell line].
AB  - The aim of this study was to explore the synergistic effect of arsenic trioxide
      and bortezomib on apoptosis of Raji cell line. The cells were treated with
      arsenic trioxide, bortezomib, low-dose arsenic trioxide combined with bortezomib,
      respectively. The cell viability and proliferative curve were estimated by trypan
      blue dye exclusion. The cell apoptosis and cell cycle status were analyzed by
      flow cytometry. The apoptosis related elements such as caspase-3, BCL-2, BAX,
      JNK2 and IkappaB-alpha, were measured with Western blot. The results showed that
      compared with cells treated with mentioned above drugs alone, the proliferative
      potential of cells in combination group was significantly inhibited (p < 0.01),
      and apoptosis rate markedly increased (p = 0.001), while obvious cell cycle
      arrest was not observed. On the protein level, the expression of Caspase-3, BAX
      and IkappaB-alpha increased, while the expression of BCL-2, and JNK2 decreased.
      It is concluded that low-dose arsenic trioxide combined with bortezomib
      synergistically induced apoptosis in Raji cell line which may be mediated by
      inhibiting NK-kappaB and JNK2 signaling.

PMID- 18718064
TI  - [Effect of pax5 gene blocked by RNAi on biological characteristics of B cell
      malignant lymphoma].
AB  - This study was aimed to investigate the biological characteristics of B
      hematological tumor cells such as proliferation, immunological phenotype and
      apoptosis by silencing pax5. The specific pax5 small hairpin RNA (shRNA) was
      synthesized by in vitro transcription. For evaluating the inhibition efficiency,
      the expression change at mRNA and protein levels were assessed by real-time RT
      PCR and Western blot respectively. To detect the biological characteristics of
      pax5-silenced hematological tumor cells, the immunological phenotype, apoptosis
      and cell proliferation were measured by using real-time RT-PCR, MTT assay and
      flow cytometry respectively. The results showed that two shRNA were synthesized,
      both of which were effective to block pax5 expression. After being blocked by
      RNAi the immunological phenotype of pax5-silenced lymphoma cells was changed, the
      expressions of CD19 mRNA and protein were reduced, but the expression of IgM was
      not changed. As compared with control group, the effect on proliferation and
      apoptosis of lymphoma cells not could be detected after pax5 silencing. It is
      concluded that the pax5 plays important role in late differentiation of B cells,
      and may participate in signal transduction of lymphoma cells, but the effect on
      proliferation and apoptosis of lymphoma cells were not detected after RNAi, which
      need to be elucidated further.

PMID- 18718065
TI  - [Antiproliferative effect of curcumin combined with cyclophosmide on the growth
      of human lymphoma cell line HT/CTX with drug resistance and its relation with
      FA/BRCA pathway].
AB  - The aim of this study was to investigate the antiproliferative effect of curcumin
      combined with cyclophosmide on the growth of human lymphoma cell line HT/CTX with
      drug resistance and its relation with FA/BRCA pathway. The inhibitory effects of
      the drugs on the growth of HT/CTX cells were determined by MTT assay. Cell cycle
      phase and apoptosis were analyzed by flow cytometry. The expression of FANCD2
      protein in FA/BRCA pathway was determined by Western blot. The results indicated
      that the combination of curcumin with CTX had an additional synergistic
      inhibitory effects on the proliferation and cell cycle distribution of HT/CTX
      cells. The curcumin could enhance toxicity of CTX on HT/CTX cells through
      inhibition of FA/BRCA pathway which was realized by suppression of FANCD2
      monoubiquitination. The curcumin combined with CTX could increase apoptosis
      inducing effect on HT/CTX cells, while the curcumin or CTX alone did not showed
      this effect, and without inhibition of FA/BRCA pahtway. It is concluded that
      combination of curcumin and CTX produces synergistic effects and reverses
      multiple drug resistance of HT/CTX cells effectively. The prevention of cells
      from entering the next cell cycle and down regulation of FANCD2 protein
      monoubiquitination may be involved in the mechanism.

PMID- 18718066
TI  - [Mutation of mitochondria cytochrome oxidase gene in patients with
      myelodysplastic syndrome].
AB  - The relationship between mitochondria gene mutation and hematological
      malignancies has been focusing on as a key point in recent studies. This study
      was aimed to investigate whether in patients with myelodysplastic syndrome (MDS)
      exists mitochoudria cytochrome oxidase COI and COII gene mutations different from
      normal tissues and to analyze whether these mutations are "hot spot" mutations.
      Eighteen MDS patients aged from 20 to 70 years old were brought into this study,
      including 2 of RA, 3 of RCMD, 7 of RAEB, 5 of AML (transformation from MDS), and
      1 of MDS/MPD. The total DNA was extracted both from bone marrow cells and buccal
      cells of the same patients. A pair of primers was designed to amplify a fragment
      with 528 base pair (7181 - 7709) by PCR technique, which contained high frequency
      mutation area of cytochrome oxidase COI and COII gene based on the literature
      reports. The PCR products were purified and sequenced as bidirection to confirm
      if there is any mutation. The results of sequence of COI and COII gene from MDS
      patient bone marrow cells were compared with both the standard sequence from
      GenBank and the sequence from MDS patient buccal cells. The results showed that 3
      single nucleotide changes in 528 bp cytochrome oxidase gene fragment from 18 MDS
      patients were confirmed. They were 7674 T-->C, 7353 A-->G, and an insert mutation
      of G at 7702. The former two mutations caused isoleucine-->methionine, and
      methionine-->viline. The 7702G ins was only confirmed with marrow cells in a
      patient, and caused a frame shift, which suggested that the mutation might be
      related to MDS cells. It is concluded that some of "hot spots" of mtDNA mutation
      in cytochrome oxidase (COI, COII) gene from our MDS patients are failed to be
      confirmed, but 3 new mutations on this gene are found, which suggested that
      mitochondria DNA mutations in MDS patients still have much complexity and
      heterogeneity, mtDNA mutation may be a prophase or an accompany phenomenon of
      this disease.

PMID- 18718067
TI  - In vitro study of biological characteristics of mesenchymal stem cells in
      patients with low-risk myelodysplastic syndrome.
AB  - The myelodysplastic syndromes (MDS) include a diverse groups of clonal and
      potentially malignant bone marrow disorders. Evidences exist that
      microenvironment cells from MDS marrow show functional abnormalities, which may
      be relevant to the incidence of such a disease. Mesenchymal stem cells (MSCs) are
      a very important component of hematopoietic microenvironment. This study was
      supposed to investigate the biological characteristics and functions of MSC
      derived from patients with MDS in low-risk. MSCs from bone marrow samples of 11
      low-risk MDS patients were isolated, cultured and expanded. Morphology,
      immunophenotype and osteoblasts differentiation were analyzed. Their capacity of
      proliferation and hematopoietic supporting in vitro were measured. A real-time
      quantitative reverse transcriptase polymerase chain reaction method (RQ RT-PCR)
      was used for detecting the expression levels of relative cytokines and chemokines
      in MSC. MSCs from healthy donors were used as controls. The results showed that
      the culture-expanded cells from MDS patients displayed a typical fibroblast-like
      morphology. Cells were positive for SH2 (CD105), SH3 (CD73), Thy-1 (CD90), while
      negative for CD34 and CD45. After induction, these cells could differentiate into
      osteoblasts. The proliferative ability of MSCs in MDS patients were not different
      from those of MSC isolated from normal bone marrow (p > 0.05), however, their
      capacity of hematopoietic supporting in vitro were significantly weaker (p <
      0.05). RQ RT-PCR detection indicated that the SDF-1 gene expression level in MSCs
      of low-risk MDS patients was significantly higher than that in MSC derived from
      healthy donors (p < 0.01). It is concluded that the abnormal function of MSC
      influences the regulation of hemotopoiesis in the bone marrow microenvironment of
      MDS patients. It is worthy to further investigate the new clue in etiological
      mechanism and therapeutic strategies for MDS.

PMID- 18718068
TI  - [Effect of decitabine combined with Trichostatin A on MDS cell line SKM-1 in
      vitro].
AB  - The study was purposed to explore the effect and mechanisms of decitabine and/or
      Trichostatin A (TSA) on SKM-1 cells in vitro. The effect of decitabine and/or TSA
      on proliferation of SKM-1cells was analyzed with trypan blue exclusion; the
      differentiation of SKM-1 cells was detected by nitro-blue tetrazolium (NBT)
      reduction and flow cytometry; the apoptosis of cells was measured by Annexin V
      FITC; the mRNA expression of Fas, survivin and P15(INK4B) in cells treated with
      decitabine and/or TSA was evaluated by RT-PCR. The results showed that decitabine
      and/or TSA were capable of inhibiting SKM-1 cell growth and promoting cell
      differentiation; they stimulated the expression of CD14 and CD11b and inhibited
      HLA-DR expression; meanwhile and decitabine or/and TSA could induce cell
      apoptosis, up-regulate mRNA expression of Fas and P15(INK4B), and down-regulate
      survivin mRNA expression. It is concluded that decitabine can induce
      apoptosis/differentiation of SKM-1 cells, whose mechanisms may related to the
      expression of Fas, survivin and P15(INK4B). Decitabine has the synergistic effect
      with TSA.

PMID- 18718069
TI  - [DNA content and cell cycle analysis of myeloma cells in patients with multiple
      myeloma].
AB  - The study was aimed to investigate the genetic background and proliferation
      characteristics of multiple myeloma (MM). Myeloma cells were isolated from bone
      marrow of 19 MM patients by direct immunomagnetic cell sorting and the DNA
      content and cell cycle analysis were carried out by flow cytometry. The results
      showed that in 4 patients the myeloma cells were found to be hyperdiploid and in
      15 patients those were found to be diploid respectively by DNA content analysis;
      the proportion of plasm cells from normal controls in S + G(2)/M phase was (1.15
      +/- 0.60)%, and that of myeloma cells from MM patients was (10.06 +/- 12.60)%
      which was significantly higher than that in the former (p = 0.001). The incidence
      of hyperdiploid in newly diagnosed patients was 11.76%, and that of treated
      patients was 100.00% which was significantly higher than that in the former (p =
      0.035); the proportion of myeloma cells from newly diagnosed patients in S +
      G(2)/M phase was (7.12 +/- 4.98)%, and that of treated patients was (35.10 +/-
      32.56)% which was also significantly higher than that in the former (p = 0.001).
      It is concluded that the variety of myeloma cells in DNA content and cell cycle
      suggests the complicated genetic background and abnormal proliferation of MM,
      which relate with the course of disease to some extent.

PMID- 18718070
TI  - [Measurement of serum free light chains and its clinical significance in 20 newly
      diagnosed patients of multiple myeloma].
AB  - The objective of this study was to explore the clinical significance of measuring
      serum free light chains (sFLC) and to compare with serum total light chains (free
      and binded) in multiple myeloma (MM). sFLC in 20 newly diagnosed MM patients and
      20 cases of healthy people as control were measured by immuno-nephelometric
      assays; the serum light chains and kappa/lambda ratio were measured in all
      patients, while immunofixation electrophoresis (IFE) tests were carried out at
      the same time in 18 out of 20 patients. The results showed that the abnormality
      of serum free light chains and kappa/lambda ratio were found in all of the 20
      newly diagnosed MM patients (p < 0.01). The measurement of sFLC showed higher
      sensitivity than the total serum chains (p < 0.01). It is concluded that the
      method testing sFLC by immuno-nephelometric assay combined with kappa/lambda
      ratio is valuable for MM diagnosis, and the measurement of sFLC can be used as
      one of indicators for MM diagnosis.

PMID- 18718071
TI  - [Dynamic detection of chimerism and fusion gene in chronic myeloid leukemia
      patients relapsed after allogeneic hematopoietic stem cell transplantation].
AB  - This study was aimed to investigate the chimerism and fusion gene expression in
      patients with CML after allo-HSCT, to analyse engraftment and minimal residual
      disease by using STR-PCR combined with RT-PCR qualitative and quantitative
      assays, and to evaluate their clinical value for predicting disease relapse. 4
      relapsed patients with CML after allo-HSCT were dynamically investigated.
      Qualitative analysis of donor chimerism was performed by multiplex PCR
      amplification of STR markers and capillary electrophoresis with fluorescence
      detection, qualitative detection of bcr/abl transcripts was performed by RT-PCR.
      The results showed that the 100% donor chimerism appeared in 4 patients on day 28
      after transplantation and bcr/abl expression was negative, but the 4 patients
      were in status of unstable mixed chimerism (DC: 0% - 80.4%) at the different time
      points during the following up with bcr/abl gene positive. 2 patients of them
      were continuously mixed chimerism after relapse of CML, the other 2 changed from
      MC to CC by intervention of clinical treatment. Decreasing values of donor
      chimerism were detected prior to the occurrence of graft rejection and CML
      relapse, and bcr/abl gene expression was positive. It is concluded that the
      results of STR-PCR in the range of its sensitivity fully correspond with bcr/abl
      tests in patients. The combination of STR-PCR with RT-PCR will provide a highly
      sensitive and valuable tool for evaluating engraftment, graft rejection, and
      relapse and predicting GVHD. Furthermore, it can provide a basis for early
      intervention of clinical treatment, and can identify these high risk patients
      with molecular or cytogenetic relapse after allo-HSCT.

PMID- 18718072
TI  - [Correlation of chemokine CCL-2/MCP-1 level in the plasma with aGVHD and
      idiophathic pneumonia syndrome after allogeneic hematopoietic stem cell
      transplantation].
AB  - The aim of this study was to investigate the relationship between the plasma
      levels of chemokine CCL-2/MCP-1 and acute graft-versus-host disease (aGVHD)
      and/or idiopathic pneumonia syndrome (IPS) after allogeneic hematopoietic stem
      cell transplantation (allo-HSCT). ELISA assays were used to detect the plasma
      level of CCL-2/MCP-1 of 22 patients who received allo-HSCT, including 14 patients
      without or with grade I, 8 patients with grade II - IV aGVHD, respectively. 8 out
      of 22 patients were also diagnosed with IPS clinically. The dynamic changes of
      the plasma levels of CCL-2/MCP-1 chemokine and its correlation with aGVHD and/or
      IPS were analysized retrospectively. The results showed that the plasma levels of
      CCL-2/MCP-1 in the patients with moderate and serious aGVHD (grade II - IV)
      significantly increased, as compared with that prior to allo-HSCT (p < 0.05). The
      plasma levels of CCL-2/MCP-1 in the patients with aGVHD and/or IPS were higher
      significantly than those without any of these complications (p = 0.001). The
      retrospective analysis indicated that the plasma levels of CCL-2/MCP-1 in the
      patients with IPS significantly increased (p = 0.006). It is concluded that
      plasma level of CCL-2/MCP-1 correlates with aGVHD and/or IPS, and plays a role in
      the pathogenesis of these complications.

PMID- 18718073
TI  - [Analysis of STR loci expression after allogeneic cord blood hematopoietic stem
      cell transplantation].
AB  - The purpose of this study was to analyze the STR loci expression after allergenic
      cord hematopoietic stem cell transplantation in patient with Ducennes muscular
      dystropy (DMD) patient. PCR-SSO was used to identify the HLA antigens and
      alleles, STR-PCR was used to detect the chimera status. Quantity analysis of
      donor chimeras was performed by multiplex PCR amplification of STR marker and
      capillary electrophoresis with fluorescence detection. The results showed that
      patient appear to be HLA identical to the donor cord blood at the tested level.
      Persistent full donor chimerism was found in breast bone marrow. The patient with
      stable MC (DC < 5%) had a probability of long term survival with molecular
      remission MC status appeared in forearm muscle, tongue, liver, spleen, stomach,
      right temporal lobe, diaphragmatic muscle, bronchus, left ventricle and right
      kidney. In conclusion, the donor gene can express in parenchymatoas organs, the
      donor chimerism was detected in breast bone marrow and some other organs.

PMID- 18718074
TI  - [Factors affecting mobilization of peripheral blood stem/progenitor cells and
      apheresis efficiency from healthy donors by rhG-CSF].
AB  - This study was aimed to explore the factors impacting on effect of the
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) in mobilizing
      and collecting peripheral blood stem/progenitor cells (PBSPC) from healthy
      donors, and to determine the optimal time for PBSPC harvest. A mobilization
      course in 431 healthy donors was retrospectively studied and the factors
      influencing the efficacy of mobilization were analyzed. The normal donors
      underwent leukapheresis for PBSPC collection in multicentres after mobilization
      with G-CSF administered. A variety of items analyzed included donor age, sex,
      weight, body mass index (BMI), daily G-CSF dose and schedule of G-CSF
      administration. The results showed that G-CSF was administered subcutaneously at
      median 5.7 microg/kg for mobilization for 3 - 5 days, The median number of
      peripheral blood mononuclear cells (PBMNC) count of per kg recipient weight was
      9.57 x 10(8) and CD34(+) cells per kg recipient weight was 4.91 x 10(6) after a
      median of 1.7 leukapheresis. The side effects were mild and well tolerated. By
      univariate analysis, BMI, daily G-CSF dose and schedule of administration were
      significantly correlated with the yield of PBMNCs, CD34(+) cells. The best
      apheresis yields of PBMNCs and CD34(+) cells were achieved on day 5 after
      treatment with rhG-CSF. Because the narrow range and low dose of rhG-CSF
      administration, there were minor effects of rhG-CSF dose compared with schedule
      of administration. It is concluded that mobilization and leukapheresis are safe
      in healthy donors and that the low dose of rhG-CSF in 5-day administration are
      probably optimal for donor management.

PMID- 18718075
TI  - [Mechanism of ligustrazine promoting hematopoietic reconstitution in syngenic
      bone marrow transplanted mice].
AB  - The objective of this study was to investigate the effect of ligustrazine on the
      expression of stem cell factor mRNA (SCF) in bone marrow tissue and explore the
      mechanism of hematopoietic reconstitution after bone marrow transplantation
      (BMT). The colony forming unit of spleen (CFU-S) were counted, the survival rate
      at days 7, 14 and 21 after BMT were measured, as well as the expression level of
      SCF mRNA was detected by RT-PCR. The results showed that in ligustrazine group
      CFU-S counts on day 10 and survival rate, expression level of SCF mRNA on day 7,
      14 and 21 after BMT were higher than that in the control group (p < 0.01 or p <
      0.05). In conclusion, ligustrazine promotes the recovery of hematopoietic cells
      in bone marrow, enhances the repair of bone marrow microvessels, and then
      improves bone marrow microenvironment and promotes hematopoietic reconstitution.

PMID- 18718076
TI  - [BMP-4 and VEGF promote development of hematopoietic stem cells during the
      embryoid body formation from embryonic stem cells].
AB  - The objective of this study was to explore the effects of BMP-4 and VEGF on the
      development of primary hematopoietic stem cells during the differentiation of
      embryonic stem cells (ESCs) into embryoid body (EB). Murine E14 ESCs were seeded
      into semisolid methylcellulose-based medium for EB formation. According to added
      or not cytokines, experiments were divided into: (1) group of spontaneous
      differentiation without cytokine as control; (2) group of BMP-4 in different
      concentrations (0, 5, 15, 25 and 50 ng/ml); (3) group of BMP-4 combined with
      VEGF; (4) group of VEGF alone. EBs were collected on days 3, 6, 9, 12, 15, and
      the proportion of Flk-1(+) cells were assayed by flow cytometry. The results
      showed that in the different BMP-4 concentration groups, the proportions of Flk
      1(+) cells were significantly different, and it reached the peak values in 25
      ng/ml BMP-4 group as 6.51 +/- 1.02% at day 3 and 7.70 +/- 1.12% at day 6
      respectively, which were statistically higher than those in control group without
      BMP-4 and in 5 ng/ml BMP-4 group (p < 0.05). When BMP-4 was used in combination
      with VEGF, Flk-1(+) cells went to peak proportion value at day 9 as 27.53 +/-
      8.14%, which was statistically higher than that in spontaneous differentiation
      group as 8.77 +/- 2.35% (p < 0.05) and VEGF treatment group as 11.21 +/- 2.23% (p
      < 0.05). It is concluded that BMP-4 in combination with VEGF can promote Flk-1(+)
      cells genesis during EB formation in vitro, which provides experimental evidence
      for researches on directed differentiation of ESCs into hematopoietic stem cells
      simulating the microenvironment in vivo.

PMID- 18718077
TI  - [Effects of different doses of thrombopoietin on proliferation of bone marrow
      mesenchymal stem cells in mice].
AB  - To explore the effect of different doses of thrombopoietin on proliferation of
      bone marrow mesenchymal stem cells (MSCs) in mice, 20 Kunming mice (35 +/- 5 g)
      were divided randomly into 4 groups: low-dose TPO group, moderate-dose TPO group,
      high-dose TPO group and normal control group (n = 5). The experimental groups
      were subjected to intraperitoneal injections of TPO at a dose of 25, 50, 100
      microg/kg, respectively, and normal control group were treated with saline at a
      dose of 0.1 ml/g per day for 5 days. The bone marrow was harvested on 12 hours
      after the final administration. The bone marrow nucleated cells (BMNCs) were
      counted and seeded at a density of 10(6) cells/cm(2). The colony-forming unit
      fibroblast (CFU-F) of MSCs was cultured and evaluated. The CFU-F of MSCs
      underwent osteo-genic induction and adipogenic induction, and cytochemical and
      immunocytochemical staining were performed to verify their multipotential. CFU-F
      and the cell percentage of CD90(+), CD105(+), CD34(+) in BMNCs were analyzed by
      flow cytometry. The results showed that the number of BMNCs and the cell
      percentage of CD90(+), CD105(+), CD34(+) and CFU-F increased obviously in TPO
      groups as compared with the normal control group (p < 0.05). The number of BMNCs
      increased most obviously in the 50 microg/kg TPO group. However, there was no
      significant difference in number of CFU-F between 50 microg/kg and 100 microg/kg
      TPO group (p > 0.05). The CFU-F of MSCs in bone marrow had their osteogenic and
      adipogenic differentiation potentials in vitro. It is concluded that the number
      of BMNCs and the cell percentage of CD90(+), CD105(+) and CFU-F increased after
      administration with TPO. It means that TPO can enhance MSCs to proliferate in
      bone marrow. However, the number of BMNCs and CFU-F can not increase with the
      increase of TPO dose.

PMID- 18718078
TI  - [Effect of bone marrow mesenchymal stem cells on T-cell subgroups].
AB  - The aim of this study was to investigate the effect of human bone marrow
      mesenchymal stem cells on human T-cell proliferation resulted from stimulation
      with PHA and possible immunomodulating mechanism. T cells were positively
      selected by CD3(+) magnetic beads, and were then co-cultured with irradiated MSCs
      overnight before the addition of PHA. T-cell proliferation was measured by BrdU
      assay and the degree of apoptosis was assessed by flow cytometry with Annexin
      V/PI. T cells co-cultured with or without MSCs were treated with PHA for 72
      hours, then harvested. They were labeled with anti-CD4, anti-CD8, anti-CD25
      antibodies and analyzed by flow cytometry. The results showed that MSCs inhibited
      T-cell proliferation, but did not induce T cell apoptosis. There were no
      significant changes in the ratio of CD4(+) and CD8(+) T cells of MSC-treated
      group, as compared with the control group. After stimulation with PHA, there was
      an increase in CD4(+) T cells and decrease of CD4(+)CD25(+) cells in MSC co
      cultured group. It is concluded that the MSCs inhibit T-cell proliferation after
      stimulation with PHA, and show more inhibitive effects on CD8(+) and CD4(+) T
      cells, but CD25(+) regulatory T cells may not be involved in this process.

PMID- 18718079
TI  - [Large scale expansion of hematopoietic progenitor cells from umbilical cord
      blood by magnet stirred culture system].
AB  - The aim of this study was to expand hematopoietic progenitor cells at large scale
      by magnet stirred culture system. Mononuclear cell from umbilical cord blood were
      cultured in serum-free medium with stem cell factor, FIT-3 ligand and
      thrombopoietin. Firstly, the role of magnet on cell growth and colony-forming was
      studied by static culture on 0, 25 and 50 mT. Then the expansion multiple of
      cells, colony-forming and expression of surface markers were studied in magnet
      stirred culture by cell counting, colony-forming assay and flow cytometry. The
      results indicated that there was no difference in multiple of total cell
      expansion and numbers of hematopoietic colonies between 0, 25 and 50 mT groups
      and spinner groups (all p > 0.05). After 7 day cultures, the multiple of total
      cell expansion in magnet stirred culture was higher than that in static culture
      (p < 0.01). The numbers of CFU-GM (colony-forming unit-granulocyte/macrophage)
      and CFU-E (erythroid colony forming unit) in magnet stirred culture were higher
      than those in static culture, (p < 0.05). The primitive cells (CD34(+),
      CD34(+)/CD38(-) or CD133(+)) of the expanded cells in magnet stirred culture were
      less than those in static culture (p < 0.05). However, the CD184(+) or CD62L(+)
      expanded cells were more than that in static culture (p < 0.05). It is concluded
      that magnet stirred culture favors the expansion of hematopoietic progenitor
      cells. The results will be finally confirmed in further in vivo experiments and
      clinical applications.

PMID- 18718080
TI  - [Expression and function of non-muscle myosin-IIA in Fechtner syndrome].
AB  - The study was purposed to investigate the expression and function of non-muscle
      myosin heavy chain-IIA (NMMHC-IIA) in Fechtner syndrome in order to explore the
      pathologic changes of kindy disease and the mechanism of granulocyte inclusion
      body formation. NMMHC-IIA levels in granulocytes were analyzed by Western-blot,
      the expressions of NMMHC-IIA, IIB in HEK-293 cells were detected by RT-PCR and
      were analyzed by co-immunoprecipitation. The results indicated that the IIA/beta
      actin ratio for Fechtner syndrome granulocytes was (0.35 +/- 0.12), and obviously
      decreased as compared with that of normal control (0.87 +/- 0.18) (p < 0.01). The
      IIA and IIB expressed higher in HEK-293 cells. The interaction of IIA and IIB was
      confirmed by co-immunoprecipitation in HEK-293 cells. It is concluded that
      dominant-negative effect of NMMHC-IIA is involved in the formation of inclusion
      bodies. IIA and IIB show obvious interaction, IIB partly compensates the IIA
      defect derived from MYH9 mutations, and may delay or prevent the development of
      clinically relevant abnormalities.

PMID- 18718081
TI  - [Role of CD4(+) CD25(high) T cells in the pathogenesis of idiopathic
      thrombocytopenic purpura].
AB  - This study was aimed to investigate the expression level of CD4(+) CD25(high) T
      cells in peripheral blood of patients with idiopathic thrombocytopenic purpura
      (ITP) before and after treatment and to explore its significance in pathogenesis
      of ITP. The expressions of CD4(+) CD25(high) T cells in peripheral blood of 20
      ITP patients before treatment, 20 ITP patients after treatment and 14 normal
      individuals (control) were detected by immunofluorescence and flow cytometry. The
      result showed that the expression of CD4(+) CD25(high) in ITP group before
      treatment was evidently lower than that in treated ITP group and control (p <
      0.01), but there was no remarkable difference between the treated ITP group and
      the control group p > 0.05). In conclusion, the expression of CD4(+) CD25(high) T
      cells in the ITP group before treatment was evidently lower than that in the
      control group, which becomes higher than before when the patients showed
      effective response to the treatment. Correlation of CD4(+) CD25(high) T cell
      expression rate in peripheral blood with platelet level was positive. Therefore
      the expression level of CD4(+) CD25(high) T cells can be used as an effective
      index to judge the ITP prognosis. Further study of CD4(+) CD25(high) T cells
      regarded as an immune target is needed.

PMID- 18718082
TI  - [Expression of coagulation factor IX gene mediated by human source vector pHrnF9
      in intestinal epithelial sw480 cells].
AB  - The objective of this study was to explore the feasibility of intestinal
      epithelial cell and human source vector used in gene therapy for hemophilia B.
      The intestinal epithelial sw480 cells were transfected with human source vector
      plasmid pHrnF9 which contained human coagulation factor IX gene. Transcription of
      its mRNA were measured by RT-PCR. The transfection efficiency were observed under
      fluorescence microscope. The expression of its protein and coagulant activities
      in the transfected sw480 cells were measured by ELISA and one-stage method. The
      results showed that the expression of hFIX mRNA could be detected after
      transfection. The transfection efficiency reached to the maximum at 48 hour. The
      hFIX protein amount was 11.3 +/- 0.23 ng/(10(6) cells.24 h) at 24 hours after
      transfection and reached to 29.34 +/- 1.00 ng/(10(6) cells.24 h) at 48 hours and
      decreased to 12.45 +/- 0.15 ng/(10(6) cells.24 hr) at 72 hours. Sw480 cells
      transfected with pHrnF9 were capable of producing hFIX with coagulant activity.
      The coagulant activity reached to (6.07 +/- 0.17)%/10(6) cells at 48 hours and
      decreased to 1.81 +/- 0.06%/10(6) cells at 72 hours. It is concluded that the
      sw480 cells transfected with pHrnF9 plasmid can express hFIX with coagulant
      activity, the intestinal epithelial cells may become target cells in the gene
      therapy for hemophilia B.

PMID- 18718083
TI  - [Hemostatic effect of hemocoagulase agkistrodon and its mechanism].
AB  - This study was aimed to investigate the hemostatic effects of hemocoagulase
      agkistrodon (HCA) and its mechanism. The procoagulative and hemostatic effects of
      HCA were evaluated by using rabbit blood coagulatin time and mouse tail bleeding
      time; the mechanisms of HCA hemostatic effect were analyzed by using rabbit blood
      clot lysis and fibrinogen lysis. The results showed that HCA shortened the rabbit
      blood coagulation time and the mouse tail bleeding time significantly. The
      effects are nearly similar to that of positive control (reptilase). HCA also
      induced rabbit blood clot lysis and directly hydrolysed the alpha-chain of
      fibrinogen. It is concluded that HCA exert its hemostatic effects by hydrolysing
      the alpha-chain of fibrinogen, but it is not able to induce production of XIII
      factor.

PMID- 18718084
TI  - Immunoregulatory effect of evodiamine in mice of various germlines.
AB  - The aim of this study was to investigate the effect of evodiamine on the
      proliferation and the immune function of thymocytes and splenocyte of mice from
      three germlines, which were 8 weeks old masculinity BALB/c, C57BL/6 and F1
      hybridization mice. Cells of thymus and spleen were harvested and prepared as
      unicellular suspension. Cell proliferation was detected by MTT method, while the
      concentration of IL-2 was detected by ELISA, mRNA levels of bcl-2 and cdk2 in
      cells treated with evodiamine were detected by RT-PCR, the apoptosis rate and
      intracellular reactive oxygen species (ROS) concentration were analyzed by FCM,
      and the protein levels of BCL-2, CDK2 and BAX were determined by fluorescence
      microscope. The results indicated that at 0.5, 0.75 and 1 micromol/L, evodiamine
      inhibited the proliferation and externalization of thymocytes and splenocytes
      stimulated with ConA (p < 0.05). At 0.75 micromol/L, evodiamine inhibited the
      secretion of IL-2, decreased the mRNA level of bcl-2 and cdk2, and induced
      apoptosis of thymocytes and splenocytes (p < 0.05). Intracellular ROS
      concentration increased significantly after treatment with evodiamine for 12
      hours (p < 0.05). The death rate increased at a prolong period of time. After
      treatment with evodiamine for 24 and 48 hours, the cells were divided into two
      groups, one of which was negatively stained by 2 7-dichlorofluorescein (DCF),
      which indicated that ROS level decreased significantly in the dying cells. It is
      concluded that evodiamine inhibits proliferation and induces apoptosis of
      thymocytes and splenocytes from different germline mice, and at the same time
      decreases secretion of IL-2 through down-regulating bcl-2 and cdk2 levels.

PMID- 18718085
TI  - [Anti-leukemia activity of T cells impacted by dendritic cells added with sodium
      selenite].
AB  - The study was purposed to explore the quantity, morphology and immunophenotype of
      dendritic cells (DC) acquired by co-cultivated system with 3 types of cytokines
      and sodium selenite (Se) from peripheral blood mononuclear cells (PBMNCs), and to
      investigate the effects of Se on inducing the cytotoxic T lymphocyte (CTL) to get
      specific anti-leukemic activity in vitro by DC pulsed with K562 cell frozen
      thawed antigen (antigen cell loading). PBMNCs isolated from healthy donors were
      cultured in RPMI 1640 medium contained 10% FBS supplied with 3 cytokines (rhGM
      CSF, rhIL-4, TNF-alpha) for 4 days, DCs harvested were divided into 4 groups,
      DCI: DC alone; DCII: DC + Se (adding 0.5 micromol/L of Se); DCIII: DC + K562
      (pulsed with lysed K562 cells); DCIV: DC + Se + K562. Morphology of DCs was
      observed under microscope at day 7. The CD1a, CD40, CD83, and CD86 were detected
      by FCM. Cytotoxicity of T cells induced by DC were measured with LDH release test
      at day 12. The level of IL-12 in supernatant of cultured DCs were determined with
      ELISA. The results indicated that at 7th day DC in 4 groups showed characteristic
      morphology, the colony numbers of 4 groups were all higher than those before
      cultivation. There were no obvious differences of morphology and colony counts
      between DCI group and DCII group. The colony numbers of DCIII group and DCIV
      group increased, as well as the ratio of suspended cells enhanced. The
      expressions of CD1a, CD40, CD83 and CD86 in 4 groups of DC were significantly
      higher than those in PBMNC group (p < 0.01), the expressions of CD1a and CD40 in
      4 groups of DC did not display significant difference (p > 0.05), the expressions
      of CD83 and CD86 in both DCIII group and DCIV group were all higher than those in
      DCI group and DCII group (p < 0.01), but their expressions of CD83 and CD86 in
      DCI and DCII were not significantly different (p > 0.05), as well as those in
      DCIII group and DCIV group. With the ratio of 25:1 between E:T, killing rate of
      CTL on K562 cells in 4 DC groups were 15.3 +/- 2.3%, 26.3 +/- 3.7%, 28.2 +/- 4.5%
      and 36.2 +/- 3.7% respectively, all obviously higher than those of T cell group
      without being sensitized by DCs (5.9 +/- 2.4%) (p < 0.01), The CTL effect in DCIV
      group was the highest, which was higher than those in other 3 DC groups (p <
      0.01); the effects in both DCII and DCIII group were also higher than that in DCI
      group (p < 0.01), but their difference between DCII and DCIII groups did not show
      significance (p > 0.05). The levels of IL-12 in supernatant of DCI, DCII, DCIII
      and DCIV groups were 257.0 +/- 64.2, 328.1 +/- 43.9, 323.0 +/- 53.5 and 353.9 +/-
      46.2 pg/ml respectively, all significantly higher than that in supernatant of T
      cell alone group without being sensitized by DCs (35.27 +/- 27.1 pg/ml) (p <
      0.01), The levels in DCII, DCIII and DCIV groups were all higher than that in DCI
      group (p < 0.01), but their levels between DCII, DCIII and DCIV groups were not
      of significant difference (p > 0.05). It is concluded that matured DCs can be
      successfully obtained from PBMNCs by a culture system contained rhGM-CSF, rhIL-4
      and TNF-alpha with or without low-dose of Se (0.5 micromol/L) in vitro. Using
      K562 cell frozen-thawed antigen, DC express more adhesive molecules and co
      stimulating molecules (CD83, CD86), and increase the secretion of IL-12, as well
      as the killing effects of CTL on special target cells. Low dose of Se did not
      showed effects on quantity and morphology of matured DC harvested, as well as
      their expression of mature phenotypes, it raised levels of IL-12 secreted by DCs,
      reaching the same level as using K562 cell frozen-thawed antigen, and it showed
      synergistic effect on induction of CTL with K562 cell frozen-thawed antigen.

PMID- 18718086
TI  - [Effect of dendritic cells on expansion and function of autologous natural killer
      cells in vitro].
AB  - The objective of this study was to investigate the effect of dendritic cells
      (DCs) on expansion and function of autologous natural killer (NK) cells and its
      mechanism in vitro. NK cells were expanded from peripheral blood mononuclear
      cells (PBMNCs) of healthy volunteers in stem cell growth medium (SCGM)
      supplemented with rhIL-2 (control group) in 24-well culture plates at 37 degrees
      C in a humidified CO(2)-containing atmosphere. NK cells were cultured with
      autologous DCs in the ratio of 5 to 1 (group 5:1) or 1 to 1 (group 1:1) from day
      10 after expansion. Total cells of every group were counted and the expression of
      CD3, CD16/56 on the surface of NK cells was assayed by flow cytometry on days 7,
      14 and 21 to calculate the expansion of NK cells. Cytotoxicity of expanded NK
      cells against K562 cells was assayed by MTT method. TNF-alpha and IL-12p70 were
      detected in culture supernatants by sandwich ELISA. The results indicated that
      the expansion and cytotoxicity of NK cells were improved after mixed with
      autologous DCs. Furthermore, when DCs were mixed with NK cells, the ratio of DCs
      to NK cells was higher, the expansion and cytotoxicity NK cells were higher. On
      day 14, the expansion multiple in control, group 5:1 and group 1:1 were 16.26 +/-
      1.58, 29.25 +/- 4.01 and 21.23 +/- 2.91 respectively. The expansion multiple of
      group 5:1 was much higher than that of the other two groups (p < 0.05). The
      expressions of CD3(-), CD56/16(+) on surface of NK cells in control, group 5:1,
      group 1:1 were (34.8 +/- 5.1)%, (64.6 +/- 7.8)% and (50.6 +/- 8.7)% respectively
      and that of group 5:1 was the highest (p < 0.05). The cytotoxicities against K562
      cells in control, group 5:1 and group 1:1 were (63.7 +/- 3.8)%, (87.4 +/- 6.8)%
      and (75.4 +/- 6.3)% respectively. The cytotoxicity of group 5:1 was higher than
      that in the other two groups also (p < 0.05). TNF-alpha and IL-12p70 levels in
      culture supernatants when DCs and NK cells were mixed in the ratio of 5 to 1 were
      much higher than those in culture supernatants of DCs and NK cells alone or in
      culture supernatants when DCs and NK cells were mixed in the ratio of 1 to 1 (p <
      0.05). It is concluded that the expansion and cytotoxicity of NK cells can be
      improved by DCs and it depended on the mixed ratio of DCs to NK cells. The
      elevated expansion of NK cells by DCs bears relation to IL-12 produced by DCs.
      The enhanced cytotoxicity of NK cells is associated with TNF-alpha secreted by NK
      cells.

PMID- 18718087
TI  - [Preparation of rhIL-11 from fusion protein by using enterokinase].
AB  - The study was aimed to investigate the technological parameters of rhIL-11
      preparation from fusion protein by using enterokinase. Fusion expression vector
      pET32a/IL-11 was transferred into E.coli BL21 (DE3) pLysS and its expression was
      induced by IPTG, the lysis supernatant of the engineering strain was purified by
      Ni-NTA resin and then the target rhIL-11 was digested by auto-cleavaged DsbA-EKL
      (His)(8). The results showed that after affinity chromatography, Trx-IL-11 was
      obtained with the yield of 11.25mg/g, the purity of 89.2% and the recovery of
      91.8%. Finally the target rhIL-11 was digested and purified to over 95%. In
      conclusion, the preparation method of rhIL-11 from fusion protein by using
      enterokinase is simple and feasible with good separation, which can meet
      industrial requirements.

PMID- 18718088
TI  - [Construction and expression of a fusion protein containing extracellular domain
      of human Jagged1 and Fc fragment of human IgG1 in Pichia Pastoris].
AB  - In order to construct a pichia pastoris expression vector containing the
      extracellular domain of human Jagged1 and the Fc fragment of human IgG1 fusion
      gene, or containing only the Fc fragment of human IgG1 and to express them in
      pichia pastoris. The extracellular domain of human Jagged1 gene was cloned from
      normal human bone marrow cells. After DNA sequencing, the extracellular domain of
      Jagged1 gene was inserted into pIC-Fc vector constructed previously, which is
      Pichia pastoris expression vector containing only the Fc fragment of human IgG1.
      The constructed plasmid was transformed into yeast GS115 by means of
      electroporation. The recombinant transformants with a high copy number of the
      plasmid were selected on MD plate with G418. The expression of protein was
      induced by addition of methanol. Then, protein expression was analyzed by SDS
      PAGE. The results indicated that the extracellular domain of human Jagged1 gene
      was effectively amplified. The DNA sequencing result showed that the constructed
      plasmid containing hJagged1(ext)-Fc fusion gene was the same as designed. The
      fusion protein was successfully expressed in Pichia pastoris. It is concluded
      that the hJagged1(ext) gene has been successfully cloned and expressed, which
      provides a new fusion protein for further experiments, the hJagged1(ext)-Fc
      fusion protein can be used as a new stimulator for proliferation of hematopoietic
      stem/progenitor cells in vitro.

PMID- 18718089
TI  - [Expression and analysis of HLA-A, B and DRB1 genes in patients with chronic
      myelogenous leukemia in Guangdong area].
AB  - To study the gene polymorphism of HLA-A, B, DRB1 alleles in patients with chronic
      myelogenous leukemia and to explore the correlation of HLA with chronic
      myelogenous leukemia, the polymerase chain reaction-reverse sequence specific
      oligonucleotide (PCR-RSSO) was used to analyze the polymorphism of HLA-A, B, DRB1
      alleles of 293 CML Patients and 406 randomized and synchronous blood donors
      (healthy and unrelated with patients) from Guangdong Han population. The results
      indicate that the gene frequency of HLA-A*24 in CML group was 15.53% lower than
      that of control group (22.09%, RR = 0.63, p = 0.005); the gene frequency of HLA
      B*13 in CML group was 10.41% higher than that of control group (6.74%, RR = 1.68,
      p = 0.016). The gene frequency of HLA- DRB1*14 in CML group was 7.51% lower than
      that of control group (11.89%, RR = 0.58, p = 0.008). The differences were all
      statistically significant. It is concluded that the gene frequency of HLA-A*24,
      HLA- DRB1*14 in CML patients is significantly lower than normal people in
      Guangdong. The gene frequency of HLA-B*13 in CML patients is significantly higher
      than normal people in Guangdong. Further study is needed to make sure whether HLA
      A*24 and HLA- DRB1*14 are protective gene markers for CML acquisition on
      Guangdong Chinese Han population and whether HLA-B*13 is a gene marker for CML
      susceptibility on this population.

PMID- 18718090
TI  - [Frequency of ABO type IgM antibody in 276 infants younger than six months].
AB  - The aim of study was to explore the frequency of ABO type IgM antibody in infants
      younger than six months. 309 hospitalized infants younger than six months were
      selected at first and their EDTA K(3) anticoagulant blood samples were taken. All
      the infants were divided into five groups: neonates within 1 week as group I;
      neonates aged 8 to 14 days as group II; neonates aged 15 days to 1 month as group
      III; infants aged two to 3 months as group IV and infants aged 4 to 6 months as
      group V. The monocolonal anti-A, anti-B serums, A cells, B cells and O cells were
      utilized to carried out the blood typing with tube test. The results indicated
      that from 309 samples tested 33 AB type sample were excluded. Out of the remains
      of 276 samples, 29 of 46 samples in group I were positive and with the ABO type
      consistent rate 63% (29/46); 41 of 64 samples in group II were positive and with
      the ABO type consistent rate 64% (41/64); 47 of 74 samples in group III were
      positive and with the ABO type consistent rate 63% (47/74); 28 of 45 samples in
      group IV were positive and with the ABO type consistent rate 62% (28/45); 40 of
      47 samples in group V were positive and with the ABO type consistent rate 85%. It
      is concluded that the ABO type IgM antibody appear in most infants younger than
      six months and these IgM antibodies may be regarded as the important evidence for
      ABO typing in infants.

PMID- 18718091
TI  - [Effect of highway transportation on the quality of red blood cells].
AB  - This study was purposed to investigate the effect of highway transportation on
      the quality of blood components so as to provide experimental basis to meet the
      needs of military operations. The transport condition was simulated by random
      vibration test. The red blood cells, leukocyte-reduced red blood cells, washed
      red blood cells were randomly vibrated (C Road) for 4 hours. Then, these blood
      components were stored in refrigerator for 15 days (4 degrees C). Six milliliters
      of blood were collected before vibration, after vibration, and at day 15 days of
      storage after vibration, respectively. The suspension was isolated. The free
      hemoglobin (FHb), routine hematological parameters, and biochemical indexes were
      determined. The results showed that FHb, lactate dehydrogenase (LDH), K(+) of red
      blood cells and leukocyte-reduced red blood cells did not significantly change
      after vibration and storage. However, FHb, LDH and K(+) of washed red blood cells
      increased significantly after simulated transportation (p < 0.05). The levels of
      these parameters at day 15 of storage after vibration were also significantly
      higher than those after vibration (p < 0.01). The changes of other hematological
      parameters were not significant in three blood components after vibration (C
      Road) and storage for 15 day. In conclusion, red blood cells and leukocyte
      reduced red blood cells were qualified for clinic transfusion even after
      transportation within 4 hours for 15 day storage later, if they were kept in
      proper blood container and protected from damping. However, the washed red blood
      cells could not be used for clinic after similar transport in the military
      operations.

PMID- 18718092
TI  - [Application of thrombelastography in evaluation of platelet function during
      storage].
AB  - This study was aimed to explore changes of platelet function in vitro during
      storage by thrombelastography (TEG). 12 units plateletpheresis were randomly
      selected and stored at 20 to 24 degrees C with agitation. Thrombelastography
      variable parameters R, K values and maximal amplitude (MA) were measured on 1, 2,
      3, 4, 5 days of platelet storage. Platelet concentration, mean platelet volume
      (MPV), hypotonic shock response (HSR), CD62p expression and CD62p reexpression on
      platelet surface were detected at the same time. Changes of platelet function in
      virto were systematically evaluated by above-mentioned indexes. The results
      showed that MPV augmented slightly with prolongation of preserved time (p >
      0.05), and CD62p expression on platelet surface increased remarkably (p < 0.01),
      while CD62p reexpression decreased gradually (p < 0.01). There were no
      significant differences in HSR level of platelets during storage (p > 0.05). R
      value increased with prolongation of preserved time (p < 0.01). There were no
      obvious changes on K value and alpha Angle during storage (p > 0.05). There were
      no obvious changes in MA from 1 to 4 days, and MA decreased slightly on day 5 (p
      < 0.05). It is concluded that there was no significant change in MA and HSR which
      reflects comprehensive coagulation of platelets during storage. Platelets on the
      end of storage have excellent function of hemostasis; Thrombelastography
      parameter MA value can be used as a valuable indicator for evaluation of platelet
      function in vitro during storage.

PMID- 18718093
TI  - [Cryopreservation strengthens procoagulative activities of platelets].
AB  - The aim of this study was to explore the potential relationship between the
      enhancement of instant hemostatic function in vivo of cryopreserved platelets and
      its procoagulative related molecule activities. The ability of platelet binding
      factor V density of GPIb-IX-V (CD42a) at platelet member surface were detected by
      flow cytometry, the clotting time induced by activated platelets were evaluated
      by coagulometer and platelet count, MPV and PDW were measured by hemocytometer
      before and after fresh platelets were cryopreserved. The results showed that the
      clotting time induced by activated cryopreserved platelets decreased by 43.9%,
      even quicker than that induced by fresh platelets; the fluorescence intensity of
      cryopreserved platelet binding factor V increased by 117%, more than that of
      fresh platelets binding factor V; the GPIb-IX-V (CD42a) density at cryopreserved
      platelet membrane surface increased by 32%, higher than that at fresh platelet
      surface. It is concluded that the enhancement of instant hemostatic function in
      vivo of cryopreserved platelet may be related to higher expression of
      procoagulative molecules or to their enhanced activity and rapid hemostatic
      effect.

PMID- 18718094
TI  - [Comparison between efficacy and safety of rituximab plus CHOP regimen and CHOP
      regimen for treatment of newly diagnosed patients with diffuse large B-cell
      lymphoma].
AB  - The aim of this study was to compare the efficacy of rituximab plus CHOP regimen
      and CHOP regimen on newly diagnosed patients with diffuse large B-cell lymphoma
      (DLBCL), and analyze their toxicities. A total of 69 patients were enrolled from
      July 2003 to Dec 2006. The patients were non-randomly were divided into 2 groups:
      36 received CHOP alone (CHOP group) and 33 received rituximab plus CHOP (R-CHOP
      group). The complete response (CR) rates, overall survival (OS) and side events
      of the 2 groups were compared. The results showed that the CR rate in R-CHOP
      group was higher than that in CHOP group (69.7% vs 47.2%, p = 0.049); especially
      in patients of male, Ann Arbor III - IV and IPI 3 - 5 (p = 0.017, p = 0.005 and p
      = 0.000). The estimated mean OS in R-CHOP group was longer than that in CHOP
      group (45.7 months vs 35.2 months, p = 0.145), and also in the estimated mean
      progression free survival (PFS) (38.5 months vs. 24.6 months, p = 0.017). The
      major adverse events in combination group were infusion-related responses which
      could be well tolerated in patients, and hematological toxicities which were
      similar to those in CHOP group. In conclusions, Rituximab increases the
      therapeutic efficacy of CHOP regimen on newly diagnosed patients with DLBCL,
      without a clinically significant increase in toxicity.

PMID- 18718095
TI  - [Treatment of chronic lymphocytic leukemia with regimen of fludarabine,
      cyclophosphamide and rituximab].
AB  - In order to evaluate the efficiency of rituximab combined with fludarabine,
      cyclophosphamide and rituximab (FCR) regimen for chronic lymphocytic leukemia
      (CLL). Five patients with CLL were treated with FCR regimen for 2 - 6 courses.
      FCR regimen included fludarabine 25 mg/m(2) via intravenous drip at day 2 - 4,
      cyclophosphamide 250 mg/m(2) via intravenous drip at day 2 - 4 and rituximab 375
      mg/m(2) via intravenous drip at day 1. Courses were repeated every 4 weeks.
      Minimal residual disease (MRD) was determined by multiparametic flow cytometry.
      The results showed that three patients achieved complete remission, 2 patients
      achieved partial remission. MRD was negative in two patients. In conclusion, FCR
      is an effective therapeutic regimen for treating CLL patients and is worth to be
      used in clinic.

PMID- 18718096
TI  - [Clinical study of bortezomib in combination with dexamethasone for the treatment
      of multiple myeloma].
AB  - The objective of study was to evaluate the efficiency and safety of bortezomib
      for the treatment of multiple myeloma. Bortezomib in combination with
      dexamethasone was administered as first-line treatment in all 7 newly diagnosed
      patients with multiple myeloma. The patients with refractory myeloma were treated
      with bortezomib in combination with dexamethasone or with other traditional
      agents such as mitoxantrone and thalidomide. The results showed that according to
      the EMBT criteria, out of 7 patients one achieved complete response (CR), five
      achived partial response (PR) and one achived minor response (MR). The 3 patients
      with refractory/relapsed myeloma achieved PR (2/3) and MR (1/3). The overall
      response rate (CR + PR) was 80%. The most frequent adverse events observed were
      thrombocytopenia in three patients, diarrhea and peripheral neuropathy in one
      respectively. In conclusion, bortezomib demonstrates efficiency in the treatment
      of new-diagnosed and refractory/relapsed multiple myeloma, and the side effects
      from treatment are acceptable and manageable.

PMID- 18718097
TI  - [Application of fibrotic bronchoscopy in the diagnosis of pulmonary diffuse
      infiltration following bone marrow transplantation].
AB  - In order to evaluate the diagnostic value of fibrotic bronchoscopy (FB) in the
      pulmonary infiltration following bone marrow transplantation (BMT), 18 patients
      with pulmonary complications after BMT from November 2003 to March 2006 were
      performed with FB. Bronchoalveolar lavage (BAL) and brushing were performed in
      patients who had received short-term empirical therapy without good response, and
      transbronchial lung biopsy (TBLB) was carried out in 3 cases. The results showed
      that 9 out of 10 cases with pulmonary infection, including bacterial pneumonia (n
      = 3), aspergillosis (n = 2), pneumocystis carinii pneumonia (n = 3) and viral
      infection (n = 1) were diagnosed by using FB. One case was diagnosed as
      tuberculosis after open lung biopsy following negative results from twice BAL. 2
      out of 8 cases were diagnosed by TBLB as noninfectious pulmonary complications.
      In conclusion, FB, especially with BAL, is a safe and useful procedure for the
      evaluation of pulmonary complications, which is particularly suitable for
      diagnosis of pulmonary infection after BMT. Furthermore, TBLB should be
      recommended in order to avoid open lung biopsy, if the patients tolerate the
      operation.

PMID- 18718098
TI  - [Recent advances of CD4(+)CD25(+) regulatory T cells in pathogenesis of
      idiopathic thrombocytopenic purpura - review].
AB  - CD4(+)CD25(+) regulatory T cells are thought to be a subgroup of cells which have
      the function of immune suppression. 5 to 10 percentage of peripheral CD4(+) T
      cells and 1% - 2% of peripheral mononuclear cells are CD4(+)CD25(+) regulatory T
      cells in mouse or healthy human. They can suppress immune response through many
      pathways and sustain the stabilization of internal environment. Idiopathic
      thrombocytopenic purpura is a kind of autoimmunity disease which mainly has a
      manifestation of hemorrhage in some locations such as skin, mucosa or viscera.
      Recent findings support that CD4(+)CD25(+) regulatory T cells are relevant to the
      morbidity of idiopathic thrombocytopenic purpura. In this review, the recent
      advance on characteristics and function of CD4(+)CD25(+) regulatory T cells,
      pathogenesis of idiopathic thromocytopenic purpura and role CD4(+)CD25(+)
      regulatory T cells in pathogenesis of idiopathic thrombocytopenic purpura were
      summarized.

PMID- 18718099
TI  - [Role of NF-kappaB in hematopoietic malignancies - review].
AB  - NF-kappaB is a kind of important nuclear factors which are relative to lots of
      cellular activities such as activation of immunocyte, development of T and B
      lymphocyte, stress reaction, cell apoptosis and so on. NF-kappaB exists in almost
      all types of cytoplasm in the unreactive form of heterodimer or homodimer. Recent
      studies have shown that there is close relationship between NF-kappaB and
      pathogenesis of hematopoietic malignancies such as leukemia, lymphoma and
      multiple myeloma. In this review, the advances of studies on the role of NF
      kappaB in hematopoietic malignancies were summarized, including subunits of NF
      kappaB and its activity, activity of NF-kappaB and its effect on apoptosis,
      activity of NF-kappaB in AML cells and its mechanism, activity of NF-kappaB in
      ATL cells and its mechanism, activity of NF-kappaB in lymphoma and its mechanism,
      activity of NF-kappaB in multiple myeloma cells and its mechanism, application of
      NF-kappaB suppression in hematopoietic malignancies and so on.

PMID- 18718100
TI  - [Mechanisms underlying the expression regulation of HOXB4 transcription in
      hematopoietic stem cells - review].
AB  - As a member of the hox gene family, hoxB4 gene encodes a class of DNA-dependent
      homeobox domain nucleoprotein, which is a specific transcription factor, playing
      an important role in regulating the balance between self-renewal and
      differentiation of hematopoietic stem cells (HSCs). Therefore, it is important to
      understand the mechanisms involved in regulating expression of hoxB4 in the HSC.
      Previous studies have suggested that some hoxB4 upstream regulatory factors, such
      as USF-1 (upstream activating factor -1), USF-2 (upstream activating factor -2)
      and NF-Y complex, as well as hematopoietic cytokines, such as platelet growth
      factor (TPO) and Wnt3a protein, play important regulatory roles in the expression
      of hoxB4 in hematopoietic stem cells. In this review the structure and biological
      characteristics of hoxB4, mechanisms involved in regulating expression of hoxB4
      in the HSC are summarized.

PMID- 18718101
TI  - [Application of NOD/SCID mice in research of experimental hematology - review].
AB  - NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice are immune
      deficient mice which are made by backcross of severe combined immunodeficient
      mice with non-obese diabetic mice strains. NOD/SCID mice are both innate immune
      deficiencies and lack of T and B lymphocytes. Various tumor cells can be
      implanted in this kind of mice, the rejection and graft-versus-host disease
      (GVHD) occur fewer. Therefore, NOD/SCID mice gradually become a useful tool for
      the study on Experimental Hematology. This paper comprehensively reviews the
      biological characteristics of NOD/SCID mice, the establishment of human leukemia
      model, stem cell transplantation, drug research, deficiency and improvement of
      NOD/SCID mice in application for study.

PMID- 18718102
TI  - [Progress of research on allogeneic hematopoietic stem cell transplantation with
      reduced-intensity conditioning regimen for treatment of myelodysplastic syndrome 
      review].
AB  - Allogeneic haematopoietic stem cell transplantation (allo-HCT) is the most
      effective curative therapy in myelodysplastic syndromes (MDS). Incidence of MDS
      increases with age, peaking in the seventh decade of last century. Despite
      improved consolidation chemotherapy regimens, the prognosis of MDS in patients
      beyond 60 years of age is dismal. The introduction of peripheral blood-derived
      stem cell grafts into allogeneic HSCT and the known anti-tumor effect of donor
      lymphocyte infusions paved the way for reduced-intensity conditioning (RIC)
      allogeneic hematopoietic stem-cell transplantation, which makes transplant
      possible in advanced age, significantly alleviates transplant-related organ
      toxicity and decreases non-relapse mortality. This article reviews the advanced
      development of reduced-intensity conditioning regimens in allogeneic
      hematopoietic stem cell transplantation for myelodysplastic syndromes and the
      future of reduced intensity conditioning hematopoietic stem cell transplants
      including feasibility of RIC allo-HSCT in treating patients with MDS, selection
      of MDS cases for RIC allo-HSCT, opportunity of RIC allo-HSCT, source of stem
      cells for RIC allo-HSCT, RIC regimen for allo-HSCT, evaluation of curative
      efficacy and prognosis, GVHD and graft versus MDS, and so on.

PMID- 18718103
TI  - [Relationship between lysophosphatide acid acyltransferase beta and tumor -
      review].
AB  - Phosphatide acid (PA) is a kind of multifunctional bioactive phospholipid. It has
      been proved that PA produced by lysophosphatide acid acyltransferase (LPAATbeta)
      was involved in several signalling pathways in tumor cells, leading to the
      proliferation, apoptosis, migration, invasion, respiratory burst, expression and
      release of cytokine form tumor cells. The fact that expression of LPAATbeta was
      higher in tumor tissues than in their homologous normal tissues, and that
      antitumor effect of inhibitng LPAATbeta on solid tumor and hematological
      malignancy suggested that the targeting LPAATbeta would be a promising method of
      antitumor treatment. In this paper, the relevant basic and preclinical researches
      of LPAATbeta on antitumor treatment were summarized.

PMID- 18718104
TI  - [Research Progress of microRNAs and human hematological diseases - review].
AB  - The microRNAs (miRNAs) are an evolutionarily conserved class of 22 nucleotide (19
      - 25 nt) non-coding RNAs. The miRNAs are partially complementary to 3'
      untranslated region of target mRNA, resulting in the repression of gene
      expression at post-transcriptional level. The miRNAs have been associated with
      diverse biological processes. This review summarizes recent progress of research
      on the characteristics and function of miRNAs, and the role of miRNAs in
      hematological malignancy development.

PMID- 18718105
TI  - [American Society of Blood and Marrow Transplantation (ASBMT) Committee Report:
      collection and preservation of cord blood for personal use].

PMID- 18718106
TI  - Are autistic traits autistic?
AB  - According to the extreme male brain theory of autism (Baron-Cohen, 2002),
      autistic traits would be extreme manifestations of typical male behaviours. The
      Auyeung et al. (2009) paper establishes a link between autistic traits and higher
      fetal testosterone (fT) levels in typically developing children. We argue that
      the construct behind this relationship needs further investigation. First, the
      link between fT levels and sexually dimorphic traits, that are for example,
      associated with empathizing and systemizing, is controversial. Likewise,
      describing autistic behaviours as being extreme male-like is debatable. The
      cerebral hemisphere laterality pattern of individuals with autism also seems to
      differ from the pattern typically observed in males. Moreover, the parallel that
      should exist, according to the fT theory, between individuals with autism and
      individuals with congenital adrenal hyperplasia (CAH), because of their high fT
      levels, is unclear. The theory implying fT levels in autism fails to account for
      a big part of autism, and the link between fT and normal 'autistic traits' hardly
      demonstrates the causal link between fT and autism.

PMID- 18718107
TI  - Work-life balance and subjective well-being: the mediating role of need
      fulfilment.
AB  - The relationship between work-life balance (WLB) (i.e. the perceived sufficiency
      of the time available for work and social life) and well-being is well
      documented. However, previous research failed to sufficiently explain why this
      relationship exists. In this research, the hypothesis was tested that a
      sufficient amount of the time available increases well-being because it
      facilitates satisfaction of personal needs. Using two separate samples (students
      and employees), the mediating role of need fulfilment in the relationship between
      WLB and well-being was supported. The results suggest that perceived sufficiency
      of the time available for work and social life predicts the level of well-being
      only if the individual's needs are fulfilled within that time.

PMID- 18718108
TI  - Decision-making about pregnancy for women with cystic fibrosis.
AB  - OBJECTIVES: This study aims to generate experiential data about the decision
      making process encountered by 12 women with cystic fibrosis (CF) considering
      pregnancy. DESIGN: This study uses a qualitative grounded theory methodology to
      analyse the data and develop a conceptual hierarchical model of salient issues.
      METHODS: Twelve women completed a semi-structured interview accompanied by
      quantitative self-report measures of quality of life and psychological well
      being, and indicators of health and treatment status were used. RESULTS:
      Descriptive data demonstrated that the sample did not differ significantly from
      other published samples. Four core categories emerged: (1) impact of the
      decision; (2) preparation for making and living with the decision; (3) owning the
      decision; and (4) personal dilemmas. Each comprised a number of overlapping
      conceptual and subcategories. Influencing factors included the impact of
      pregnancy on participants' health, and upon their ability to care for the child,
      the pregnancy experiences of other women with CF, the moral implications of
      having a child and the support and beliefs of family members. DISCUSSION: The
      findings extend the current knowledge in this area. We recommend development of
      guidelines for supporting and advising chronically ill young women about the
      psychosocial and emotional issues.

PMID- 18718109
TI  - Post-traumatic growth and life threatening physical illness: a systematic review
      of the qualitative literature.
AB  - Post-traumatic growth (PTG) is the phenomenon of positive change through the
      experience of trauma and adversity (O'Leary & Ickovics, 1995). Research suggests
      that the type of trauma sustained could have differing processes and outcomes
      from each other (Demark-wahnefried et al., 2000; Sabiston, McDonough, and
      Crocker, 2007). The aim of this study was to synthesize qualitative data on PTG
      and illness related trauma. Fifty-seven published journal articles dating from
      before November 1st, 2007 in PsychINFO, MEDLINE, EMBASE, Web of Knowledge and
      from the authors own knowledge of the area were reviewed. Key words included PTG;
      benefit finding; thriving and positive changes. Key themes included: 'reappraisal
      of life and priorities'; 'trauma equals development of self'; 'existential re
      evaluation'; and 'a new awareness of the body'. Findings suggest that there are
      unique elements to illness related PTG and a need for additional research into
      the processes and outcomes of physical illness related trauma.

PMID- 18718110
TI  - Multidisciplinary allocation of chronic pain treatment: effects and cognitive
      behavioural predictors of outcome.
AB  - OBJECTIVES: Multidisciplinary treatment approaches have been found to be
      effective for chronic pain patients although there are large individual
      differences in outcomes. To increase overall treatment effects, tools are needed
      to identify patients most likely to benefit from tailored, comprehensive modular
      treatment schemes. DESIGN: The present study evaluates the effects of a
      multidisciplinary pain treatment allocation protocol in chronic pain patients and
      seeks to identify cognitive-behavioural predictors of outcome. Pain intensity,
      functional disability, depression, and use of medication in an intervention group
      of 110 chronic pain patients were compared to the outcomes of a 110 strong
      control group. RESULTS: Paired pre- and post-treatment t tests showed that all
      primary outcomes had significantly decreased in the intervention group with
      ANCOVAs revealing a main group effect for post-treatment pain intensity levels
      and functional disability. Paired t tests demonstrated both variables to have
      significantly reduced after treatment relative to the levels reported by the
      control group. Predictor analyses further showed higher levels of acceptance to
      significantly predict larger reductions in pain intensity in the intervention but
      not in the control group. CONCLUSION: The tested multidisciplinary allocation
      scheme for out-patient treatment of chronic pain complaints was effective in
      reducing pain intensity and functional disability. Findings also showed that
      especially those patients that are able to accept their condition are likely to
      profit most from the treatment in terms of pain reduction.

PMID- 18718111
TI  - Finding a pathway: information and uncertainty along the prostate cancer patient
      journey.
AB  - OBJECTIVES: To investigate the role of information in mediating the potential
      negative effects of uncertainty in prostate cancer in relation to the individual
      patient journey, conceptualized as the individual's response to his disease over
      time. DESIGN: A qualitative methodology was adopted to investigate men's
      constructions of their experience of information and its changing role in the
      management of uncertainty along the pathway of care. A cross-sectional design
      allowed comparison of the responses of men at similar stages and along different
      time points in the cancer pathway. Data collection was undertaken via focus group
      discussions and individual interviews. METHOD: Men from 4 weeks post-diagnosis to
      palliative care were recruited from hospital out-patient clinic registers and a
      local support group. Seven focus groups and 22 semi-structured interviews were
      held involving a total of 22 participants. Transcripts were analysed through a
      process of theme comparison. RESULTS: Findings suggest that uncertainty is both
      multifaceted and changing. Its impact is affected by a range of personal, disease
      related, and social factors. For some men it may bring about positive
      readjustment rather than a negative response. Effective communication of
      information by health professionals provides reassurance, knowledge, and
      understanding the balance of which varies over time and between individuals.
      CONCLUSION: Health professionals may contribute to the reduction of the negative
      effects of uncertainty through communication of information regarding process of
      care as well as medical issues. Strategies tailored to individual differences in
      information requirements and to changing needs may facilitate positive
      adjustment.

PMID- 18718112
TI  - NICE guidance and mental health: supporting change.
AB  - PURPOSE: The purpose of this article is to give those in the psychology and
      psychotherapy fields an overview of the work the National Institute for Health
      and Clinical Excellence (NICE) is doing to encourage change in response to its
      guidance. METHODS: A summary is provided of the work NICE undertakes to motivate
      others to use guidance and the practical support that is made available. Findings
      of selected studies are highlighted that demonstrate some of the successes and
      challenges relating to the uptake of NICE guidance. RESULTS: Key aspects of NICE
      work include liaison with partners at a national level to ensure work programmes
      are aligned and provision of practical support, such as the commissioning guide
      on cognitive behavioural therapy (CBT). A range of studies show that there have
      been successes in increasing the provision of psychological therapies but there
      are still variations which present challenges. CONCLUSIONS: NICE provides a
      substantial programme of support for the implementation of guidance which impacts
      on psychologists and psychotherapists. Successes in the uptake of guidance can be
      demonstrated but it is acknowledged that this is challenging area. NICE is keen
      to provide the most effective support possible for implementation so continually
      evaluates and seeks feedback on its implementation programme.

PMID- 18718113
TI  - Potential prospects of chitosan derivative trimethyl chitosan chloride (TMC) as a
      polymeric absorption enhancer: synthesis, characterization and applications.
AB  - In recent years, researchers have been working extensively on various novel
      properties of polymers to develop increased efficiency of drug delivery and
      improve bioavailability of various drug molecules, especially macromolecules.
      Chitosan, a naturally occurring polysaccharide, because of its
      protonated/polymeric nature, provides effective and safe absorption of peptide
      and protein drugs. Its transmucosal absorption is, however, limited to acidic
      media because of its strong intermolecular hydrogen bonds. A new partially
      quaternized chitosan derivative, N-trimethyl chitosan chloride (TMC), has been
      synthesized with improved solubility, safety and effectiveness as an absorption
      enhancer at neutral pH and in aqueous environment. It enhances the absorption,
      especially of peptide drugs, by reversible opening of tight junctions in between
      epithelial cells, thereby facilitating the paracellular diffusion of peptide
      drugs. This derivative thus opens new perspectives as a biomaterial for various
      pharmaceutical applications/drug delivery systems. This review deals with the
      potential use of the quaternized chitosan derivative as a permeation enhancer for
      the mucosal delivery of macromolecular drugs along with its other biomedical
      applications.

PMID- 18718114
TI  - Enhanced solubility and dissolution rate of lamotrigine by inclusion complexation
      and solid dispersion technique.
AB  - The solid-state properties and dissolution behaviour of lamotrigine in its
      inclusion complex with beta-cyclodextrin (betaCD) and solid dispersions with
      polyvinylpyrrolidone K30 (PVP K30) and polyethyleneglycol 6000 were investigated.
      The phase solubility profile of lamotrigine with betaCD was classified as AL
      type, indicating formation of a 1:1 stoichiometry inclusion complex, with a
      stability constant of 369.96+/-2.26 M(-1). Solvent evaporation and kneading
      methods were used to prepare solid dispersions and inclusion complexes,
      respectively. The interaction of lamotrigine with these hydrophilic carriers was
      evaluated by powder X-ray diffractometry, Fourier transform infrared spectroscopy
      and differential scanning calorimetry. These studies revealed that the drug was
      no longer present in crystalline state but was converted to an amorphous form.
      Among the binary systems tested, PVP K30 (1:5) showed greatest enhancement of the
      solubility and dissolution of lamotrigine.

PMID- 18718115
TI  - Compatibility of chewing gum excipients with the amino acid L-cysteine and
      stability of the active substance in directly compressed chewing gum formulation.
AB  - Using L-cysteine chewing gum to eliminate carcinogenic acetaldehyde in the mouth
      during smoking has recently been introduced. Besides its efficacy, optimal
      properties of the gum include stability of the formulation. However, only a
      limited number of studies exist on the compatibility of chewing gum excipients
      and stability of gum formulations. In this study we used the solid-state
      stability method, Fourier transform infrared spectroscopy and isothermal
      microcalorimetry to investigate the interactions between L-cysteine (as a free
      base or as a salt) and excipients commonly used in gum. These excipients include
      xylitol, sorbitol, magnesium stearate, Pharmagum S, Every T Toco and Smily 2
      Toco. The influence of temperature and relative humidity during a three-month
      storage period on gum formulation was also studied. Cysteine alone was stable at
      25 degrees C/60% RH and 45 degrees C/75% RH whether stored in open or closed
      glass ambers. As a component of binary mixtures, cysteine base remained stable at
      lower temperature and humidity but the salt form was incompatible with all the
      studied excipients. The results obtained with the different methods corresponded
      with each other. At high temperature and humidity, excipient incompatibility with
      both forms of cysteine was obvious. Such sensitivity to heat and humidity during
      storage was also seen in studies on gum formulations. It was also found that
      cysteine is sensitive to high pressure and increase in temperature induced by
      compression. The results suggest that the final product should be well protected
      from temperature and humidity and, for example, cooling process before
      compression should be considered.

PMID- 18718116
TI  - An investigation into solvent-membrane interactions when assessing drug release
      from organic vehicles using regenerated cellulose membranes.
AB  - The influence of organic solvents on artificial membranes when assessing drug
      release from topical formulations is, generally, poorly characterised yet current
      guidelines require no characterisation of the membrane before, during or after an
      experiment. Therefore, the aim of this study was to determine the effect of
      solvent-membrane interactions when using in-vitro Franz cell methods for the
      assessment of corticosteroid release and to assess compliance or otherwise with
      Higuchi's equation. The rate of beclometasone dipropionate monohydrate (BDP) and
      betamethasone 17-valerate (BMV) release across a regenerated cellulose membrane
      (RCM), from both saturated solutions and commercial formulations, was determined.
      Increasing the ratio of organic solvent, compared with aqueous phase, in the
      donor fluid (DF) resulted in up to a 416-fold increase in steady-state flux.
      Further, alterations in the receiver fluid (RF) composition caused, in some
      cases, 337-fold increases in flux. Analysis indicated that the RCM remained
      chemically unchanged, that its pore size remained constant and that no drug
      partitioned into the membrane, regardless of the DF or RF employed. However, it
      was observed that the organic solvents had a thinning effect on the RCM,
      resulting in enhanced flux, which was potentially due to the variation in the
      diffusional path length. Such findings raise issues of the veracity of data
      produced from any membrane release study involving a comparison of formulations
      with differing solvent content.

PMID- 18718117
TI  - Pharmacokinetics of tramadol in rat plasma and cerebrospinal fluid after
      intranasal administration.
AB  - We have evaluated the potential of intranasal administration of tramadol. The
      pharmacokinetic behaviour of tramadol in rat plasma and cerebrospinal fluid (CSF)
      after intranasal administration was determined and compared with those after
      intravenous and oral administration. Serial plasma and CSF samples were collected
      for 6 h, and the drug concentrations were assayed by an HPLC-fluorescence method.
      The plasma absolute bioavailability values of tramadol after intranasal and oral
      administration were 73.8% and 32.4%, respectively, in conscious rats. The Cmax
      (maximum concentration) value after the intranasal dose was lower (P<0.05), and
      the MRT (mean retention time) was longer (P<0.05) than the values obtained after
      intravenous administration. A pharmacokinetic study of tramadol in plasma and CSF
      was undertaken in anaesthetized rats. The absolute bioavailability values in
      plasma and CSF after intranasal administration were 66.7% and 87.3%,
      respectively. The Cmax values in plasma and CSF after a nasal dose were lower
      (P<0.05) than after the intravenous dose. The values of Cmax and AUC0-->6 h in
      plasma and CSF after intranasal administration were higher than after the oral
      dose. The mean drug-targeting efficiency after intranasal administration was
      significantly greater than after the oral dose. In conclusion, intranasal
      administration of tramadol appeared to be a promising alternative to the
      traditional administration modes for this drug.

PMID- 18718118
TI  - Distribution of an intravenous injectable nimodipine nanosuspension in mice.
AB  - The distribution of an intravenous injectable nimodipine nanosuspension with mean
      particle size of both 300 and 650 nm in mice was systemically investigated
      compared with that of a nimodipine ethanol formulation (Nimotop) and a
      nanosuspension coated with Tween-80. The results showed that the 650-nm
      nanoparticles provided significantly higher drug concentrations in the liver,
      spleen and lungs because of their capture by Kupffer cells in the mononuclear
      phagocyte system, but lower drug concentrations in the brain compared with
      Nimotop and smaller nanoparticles. These nanoparticles failed to give increased
      brain concentrations even when coated with Tween-80. The 300-nm nanoparticles
      could effectively increase drug concentrations in the brain and remarkably reduce
      drug concentrations in the liver, spleen and lungs, indicating that the
      nimodipine nanosuspension may be a promising formulation with no ethanol, but the
      particle size must be small.

PMID- 18718119
TI  - Protective effect of caffeine on streptozotocin-induced beta-cell damage in rats.
AB  - Many epidemiological studies have shown that coffee consumption reduces the risk
      of type 2 diabetes mellitus (T2D), although the reasons as to why remain unclear.
      In this study we investigated the effect of caffeine on pancreatic beta-cell
      damage in rats using the diabetogenic agent, streptozotocin (STZ). Wistar rats
      were given intraperitoneal injections of saline or caffeine (10, 50 or 100 mg kg(
      1)). After 15 min, the rats were injected with a citrate buffer or 65 mg kg(-1)
      STZ. Three days after injection, an oral glucose tolerance test (OGTT) was
      performed on the rats. Furthermore, three days after the OGTT, the pancreas was
      isolated and homogenized, followed by determination of insulin content. STZ
      treatment significantly increased the plasma glucose level compared with the
      control at all times during the OGTT, which was significantly diminished by
      caffeine pretreatment at all doses. STZ treatment significantly decreased the
      plasma insulin level, however, which was not recovered by caffeine pretreatment.
      Pancreatic insulin content was significantly reduced by STZ treatment compared
      with the control, which was significantly recovered by caffeine pretreatment at a
      dose of 100 mg kg(-1) (P<0.01). We showed that caffeine protects pancreatic beta
      cells against STZ toxicity. Further investigation will be required to understand
      the protective effect of caffeine against beta-cell destruction in T2D.

PMID- 18718120
TI  - Metabolic effects of various antidiabetic and hypolipidaemic agents on a high-fat
      diet and multiple low-dose streptozocin (MLDS) mouse model of diabetes.
AB  - Insulin resistance and subsequent insulin secretory defect are two main features
      of type 2 diabetes and associated metabolic disorders. The animal models of type
      2 diabetes are very complex and are as heterogeneous as the disease. We have
      evaluated the effect of various antidiabetic and lipid lowering agents
      (fenofibrate, rosiglitazone, glimepiride, metformin and simvastatin) on the
      metabolic abnormalities induced by combining a high-fat diet and multiple low
      dose streptozocin (MLDS) in mice. Male Swiss albino mice were orally treated with
      the above agents and fed with a diet containing high fat for 28 days. On day 15
      the animals were injected intraperitoneally with low-dose streptozocin (40 mg kg(
      1)), which was administered for five consecutive days. At the end of the 28-day
      treatment plasma metabolic parameters (glucose, triglyceride and immunoreactive
      insulin) were estimated. The antidiabetic and hypolipidaemic agents exhibited
      differential effects on these metabolic parameters. With the exception of
      fenofibrate all these agents reduced the plasma glucose levels, and the effects
      of metformin and rosiglitazone on glucose were found to be statistically
      significant. Although the effect of the test drugs on cholesterol was modest, a
      significant decrease in triglyceride levels was observed with sub-chronic
      treatment with these agents. Interestingly, glimepiride mildly elevated the
      insulin levels while the other antidiabetics and hypolipidaemics reduced the
      insulin levels, with metformin and rosiglitazone exhibiting statistically
      significant effects on insulin. To our knowledge this is the first report on the
      effect of various peroxisome proliferator-activated receptor modulators and newer
      antidiabetics on the metabolic effects induced by the combined high-fat diet and
      MLDS model of type 2 diabetes in Swiss albino mice. The results suggested the
      complexity of the hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia
      induced by the high-fat diet and MLDS mouse model, and their correction by
      various antidiabetics and antihyperlipidaemics may have involved diverse
      mechanisms.

PMID- 18718121
TI  - Effect of the beta-glucuronidase inhibitor saccharolactone on glucuronidation by
      human tissue microsomes and recombinant UDP-glucuronosyltransferases.
AB  - Glucuronidation studies using microsomes and recombinant uridine
      diphosphoglucuronosyltransferases (UGTs) can be complicated by the presence of
      endogenous beta-glucuronidases, leading to underestimation of glucuronide
      formation rates. Saccharolactone is the most frequently used beta-glucuronidase
      inhibitor, although it is not clear whether this reagent should be added
      routinely to glucuronidation incubations. Here we have determined the effect of
      saccharolactone on eight different UGT probe activities using pooled human liver
      microsomes (pHLMs) and recombinant UGTs (rUGTs). Despite the use of buffered
      incubation solutions, it was necessary to adjust the pH of saccharolactone
      solutions to avoid effects (enhancement or inhibition) of lowered pH on UGT
      activity. Saccharolactone at concentrations ranging from 1 to 20 mM did not
      enhance any of the glucuronidation activities evaluated that could be considered
      consistent with inhibition of beta-glucuronidase. However, for most activities,
      higher saccharolactone concentrations resulted in a modest degree of inhibition.
      The greatest inhibitory effect was observed for glucuronidation of 5
      hydroxytryptamine and estradiol by pHLMs, with a 35% decrease at 20 mM
      saccharolactone concentration. Endogenous beta-glucuronidase activities were also
      measured using various human tissue microsomes and rUGTs with estradiol-3
      glucuronide and estradiol-17-glucuronide as substrates. Glucuronide hydrolysis
      was observed for pHLMs, lung microsomes and insect-cell expressed rUGTs, but not
      for kidney, intestinal or human embryonic kidney HEK293 microsomes. However, the
      extent of hydrolysis was relatively small, representing only 9-19% of the
      glucuronide formation rate measured in the same preparations. Consequently, these
      data do not support the routine inclusion of saccharolactone in glucuronidation
      incubations. If saccharolactone is used, concentrations should be titrated to
      achieve activity enhancement without inhibition.

PMID- 18718122
TI  - Involvement of kappa opioid receptors in the inhibition of receptor
      desensitization and PKC activation induced by repeated morphine treatment.
AB  - Analgesic tolerance to morphine can develop from long-term use of this drug for
      the treatment of pain. Many reports have shown that stimulation of the kappa
      opioid receptor (KOR) suppresses development of analgesic tolerance to morphine.
      Here, we studied the KOR-mediated inhibition of morphine tolerance during
      repeated morphine treatment, with a focus on desensitization of the receptor. The
      development of analgesic tolerance to morphine during repeated morphine
      administration (10 mg kg(-1) s.c.) was completely suppressed by U-50488H (2 mg
      kg(-1) i.p.), a KOR agonist. The decrease in [35S] GTPgammaS binding activity
      stimulated by the mu opioid receptor (MOR) agonist [D-Ala2, N-Me-Phe4, Gly5-ol]
      enkephalin (DAMGO) was also significantly inhibited by U-50488H. These results
      indicate that stimulation of KOR caused by repeated morphine treatment either
      inhibits MOR desensitization or accelerates recycling of MOR on the cell surface,
      thereby suppressing morphine tolerance. Furthermore, we found that activity of
      protein kinase C (PKC) was significantly decreased in mice treated with both U
      50488H and morphine. These results suggest that the mechanisms underlying KOR
      mediated inhibition of analgesic tolerance to morphine may be partly due to
      suppression of PKC activation and prevention of receptor desensitization.

PMID- 18718123
TI  - Presence or absence of a gallate moiety on catechins affects their cellular
      transport.
AB  - The accumulation of (-)-epicatechin (EC), a non-gallate catechin, was
      significantly lower than that of (-)-epicatechin gallate (ECG), a gallate
      catechin, in Caco-2 cells. Using Caco-2 cell monolayers cultured in transwells,
      the transport of catechins in the basolateral-to-apical direction was much higher
      than that in the apical-to-basolateral direction, suggesting the involvement of
      an efflux transporter. Moreover, the results suggest that involvement of a
      transporter in EC efflux is greater than that for ECG. Treatment with transporter
      inhibitors MK571, quinidine or mitoxantrone, which inhibit MRP2, P-glycoprotein
      (P-gp) and BCRP, respectively, led to an increase in the accumulation of EC into
      Caco-2 cells and a decrease in the Papp ratio (Papp B-->A/Papp A-->B) for EC.
      These transporters seemed to be involved in EC efflux. BCRP was not an efflux
      transporter for ECG, and the influences of MRP2 and P-gp on ECG efflux were lower
      than for EC. Thus, efflux transporters appear to be responsible for the
      difference in cellular accumulation of EC versus ECG, suggesting that the
      presence or absence of a gallate moiety in the catechin structure influences the
      transporters.

PMID- 18718124
TI  - Penehyclidine prevents nuclear factor-kappaB activation in acute lung injury
      induced by lipopolysaccharide.
AB  - Penehyclidine (PHCD) has been proposed to reduce lung and lethal toxicity. The
      present study was undertaken to investigate the mechanisms responsible for the
      protective effect of PHCD against acute lung injury (ALI) in rats. Tail-vein
      injection of lipopolysaccharide (LPS; 5 mg kg(-1)) was used to induce ALI in
      rats. Secondary increases in total protein, lactate dehydrogenase activity in
      bronchoalveolar lavage fluid and myeloperoxidase in lung tissue were used to
      evaluate the effects of PHCD on ALI in rats. Activated DNA binding activity and
      expression of nuclear factor kappaB (NF-kappaB) in lung tissue were measured
      using electrophoretic mobility shift assays assay and immunohistological
      staining. Levels and mRNA expression of tumour necrosis factor alpha (TNF-alpha)
      and interleukin 1beta (IL-1beta) were measured by enzyme-linked immunosorbent
      assay and reverse transcriptase-polymerase chain reaction. Pretreatment with PHCD
      (0.03 mg kg(-1), 0.1 mg kg(-1) and 0.3 mg kg(-1) i.p.) significantly attenuated
      the LPS-induced changes in lung injury parameters and inhibited the activation
      and expression of NF-kappaB in lung tissue. Furthermore, PHCD also substantially
      reduced the LPS-induced TNF-alpha and IL-1beta mRNA expression and production in
      lung tissue and suppressed neutrophil recruitment. The results suggest that PHCD
      attenuates LPS-induced acute lung responses through inhibition of NF-kappaB
      activation and LPS-induced TNF-alpha and IL-1beta production and resulting
      neutrophil recruitment associated with acute lung inflammation and injury. PHCD
      may be a useful adjuvant to treatment strategies targeting clinical situations of
      acute inflammation.

PMID- 18718125
TI  - Hypolipidaemic mechanisms of action of CM108 (a flavone derivative) in
      hyperlipidaemic rats.
AB  - In the present study, the molecular mechanisms by which CM108, a flavone
      derivative, improves lipid profiles were investigated further. Hyperlipidaemia
      was induced by oral administration of high cholesterol and fat. After 4 weeks of
      treatment, the lipid levels in the serum, liver and faeces were measured and the
      liver genes involved in lipid metabolism were analysed to explore the molecular
      mechanisms of lowering lipids. CM108 modulated lipid profiles, including
      elevating the level of high-density lipoprotein cholesterol (HDL-C; 40%) and
      reducing serum levels of triglyceride (10%), total cholesterol (10%) and low
      density lipoprotein cholesterol (26%). Levels of triglyceride and total
      cholesterol in the liver were reduced by 18% and 24%, respectively. Increased HDL
      C level was attributed to the synergic effects of CM108 in increasing levels of
      ATP-binding cassette transporter (ABC)A1, apolipoprotein AI and apolipoprotein
      AII in the liver. Intriguingly, CM108 induced genes, including fatty acid
      transport protein, acyl-CoA synthetase and lipoprotein lipase that are important
      for more efficient fatty acid beta-oxidation, thereby reducing serum and liver
      triglyceride levels. In addition, induction of ABCG5, ABCG8 and cholesterol
      7alpha-hydroxylase contributed to cholesterol metabolism, leading to decreases in
      serum and liver cholesterol levels. Thus, the genes involved in lipid metabolism
      were systemically modulated by CM108, which contributed to the improvement of
      lipid profiles in hyperlipidaemic rats.

PMID- 18718126
TI  - Beta-escin, a natural triterpenoid saponin from Chinese horse chestnut seeds,
      depresses HL-60 human leukaemia cell proliferation and induces apoptosis.
AB  - Beta-escin, a natural triterpenoid saponin isolated from the seed of the horse
      chestnut, is known to generate a wide variety of biochemical and pharmacological
      effects. The purpose of the present study was to examine the apoptotic and
      antiproliferative activity of beta-escin in HL-60 human acute myeloid leukaemia
      cells. Antiproliferative activity was examined by soft agar colony assay and the
      trypan blue exclusion method. Apoptotic activity was evaluated by morphological
      analysis, annexin V analysis, DNA fragmentation analysis and flow cytometry cell
      cycle analysis. The results showed that beta-escin caused a significant
      inhibition of HL-60 cell proliferation in a dose- and time-dependent manner.
      Morphological evidence of apoptosis, including vacuolization, apoptotic nuclei
      fragmentation and apoptotic body formation, was observed in cells treated with 30
      microg mL(-1) of beta-escin for 24, 48 and 72 h. A significant increase in the
      population of annexin V+ and PI- cells (early apoptotic) among the total cells
      was observed in cells treated with beta-escin (30-50 microg mL(-1)) for 24 h
      (P<0.001). Typical DNA ladders, DNA with a unit length of about 180 bp, were
      detected in cells treated with beta-escin (30-50 microg mL(-1)) for 48 h by
      agarose gel electrophoresis. Flow cytometry cell cycle analysis revealed that
      beta-escin (30-50 microg mL(-1)) induced G1-S arrest and led to a significant
      accumulation of the sub-G1 population in HL-60 cells (P<0.05). Taken together,
      the results demonstrate that beta-escin is a potent natural inhibitor of cell
      proliferation and inducer of apoptosis in HL-60 acute myeloid leukaemia cells.
      The results indicate that beta-escin may be a useful candidate agent for
      exploring potential antileukaemic drugs.

PMID- 18718127
TI  - Anti-inflammatory action of Cudrania tricuspidata on spleen cell and T lymphocyte
      proliferation.
AB  - This study examined whether an extract of Cudrania tricuspidata shows anti
      proliferative effects in anti-CD3/CD28-mediated spleen and CD4+CD25- T cells and
      decreases the production of the proinflammatory cytokines interleukin-2 (IL-2)
      and interferon-gamma (IFN-gamma) in anti-CD3/CD28-mediated CD4+CD25- T cells. The
      proliferation of anti-CD3/CD28-mediated spleen cells and CD4+CD25- T cells was
      effectively suppressed by C. tricuspidata. This extract, however, did not show
      cytotoxicity in spleen cells under conditions where the antigen was not
      stimulated using CCK-8 analysis. C. tricuspidata also decreased the production of
      the pro-inflammatory cytokines IL-2 and IFN-gamma by selective inhibition of this
      extract on proliferating cells in anti-CD3/CD28-mediated CD4+CD25- T cells. These
      results suggest that C. tricuspidata may be useful in the treatment of autoimmune
      diseases and organ transplantation through the inhibitory action of T cells in
      inflammation.

PMID- 18718128
TI  - Inhibitory activities of prenylated flavonoids from Sophora flavescens against
      aldose reductase and generation of advanced glycation endproducts.
AB  - Important targets for the prevention and treatment of diabetic complications
      include aldose reductase (AR) inhibitors (ARIs) and inhibitors of advanced
      glycation endproduct (AGE) formation. Here we evaluate the inhibitory activities
      of prenylated flavonoids isolated from Sophora flavescens, a traditional herbal
      medicine, on rat lens AR (RLAR), human recombinant AR (HRAR) and AGE formation.
      Among the tested compounds, two prenylated chalcones--desmethylanhydroicaritin
      (1) and 8-lavandulylkaempferol (2)--along with five prenylated flavanones-
      kurarinol (8), kurarinone (9), (2S)-2'-methoxykurarinone (10), (2S)-3beta,7,4'
      trihydroxy-5-methoxy-8-(gamma,gamma-dimethylally)-flavanone (11), and kushenol E
      (13) were potent inhibitors of RLAR, with IC50 values of 0.95, 3.80, 2.13, 2.99,
      3.77, 3.63 and 7.74 microM, respectively, compared with quercetin (IC50 7.73
      microM). In the HRAR assay, most of the prenylated flavonoids tested showed
      marked inhibitory activity compared with quercetin (IC50 2.54 microM). In
      particular, all tested prenylated flavonols, such as desmethylanhydroicaritin (1,
      IC50 0.45 microM), 8-lavandulylkaempferol (2, IC50 0.79 microM) and kushenol C
      (3, IC50 0.85 microM), as well as a prenylated chalcone, kuraridin (5, IC50 0.27
      microM), and a prenylated flavanone, (2S)-7,4'-dihydroxy-5-methoxy-8-(gamma,gamma
      dimethylally)-flavanone (12, IC50 0.37 microM), showed significant inhibitory
      activities compared with the potent AR inhibitor epalrestat (IC50 0.28 microM).
      Interestingly, prenylated flavonoids 1 (IC50 104.3 microg mL(-1)), 2 (IC50 132.1
      microg mL(-1)), 3 (IC50 84.6 microg mL(-1)) and 11 (IC50 261.0 microg mL(-1)),
      which harbour a 3-hydroxyl group, also possessed good inhibitory activity toward
      AGE formation compared with the positive control aminoguanidine (IC50 115.7
      microg mL(-1)). Thus, S. flavescens and its prenylated flavonoids inhibit the
      processes that underlie diabetic complications and related diseases and may
      therefore have therapeutic benefit.

PMID- 18718129
TI  - Frequent inadequate supply of micronutrients in fast food induces oxidative
      stress and inflammation in testicular tissues of weanling rats.
AB  - Fast food is high in energy density and low in essential micronutrient density,
      especially zinc (Zn), of which antioxidant processes are dependent. We have
      tested the hypothesis that frequent fast food consumption could induce oxidative
      damage associated with inflammation in weanling male rats in relevance to Zn
      deprivation, which could adversely affect testis function. Zn and iron (in plasma
      and testicular tissue), plasma antioxidant vitamins (A, E, and C), as well as
      testicular superoxide dismutase (SOD) and reduced glutathione (GSH), lipid
      peroxidation indexes (thiobarbituric acid reactive substances (TBARS) and
      lipoprotein oxidation susceptibility (LOS)), and inflammatory markers (plasma C
      reactive protein (CRP) and testicular tumour necrosis factor-alpha (TNF-alpha))
      were determined. Serum testosterone and histological examination of the testis
      were performed also. We found a severe decrease in antioxidant vitamins and Zn,
      with concomitant iron accumulation. Zinc deficiency correlated positively with
      SOD, GSH, antioxidant vitamins and testosterone, and negatively with TBARS, LOS,
      CRP and TNF-alpha, demonstrating a state of oxidative stress and inflammation. We
      concluded that micronutrient deficiency, especially Zn, enhanced oxidative stress
      and inflammation in testicular tissue leading to underdevelopment of testis and
      decreased testosterone levels.

PMID- 18718131
TI  - Solid-phase microextraction in combination with GC-FID for quantification of the
      volatile free fatty acids in wastewater from constructed wetlands.
AB  - A headspace solid-phase microextraction (HS-SPME) followed by gas chromatography
      coupled to flame ionization detector (GC-FID) is developed for the direct
      determination of volatile fatty acids (VFAs) in wastewater from constructed
      wetlands. Through the investigation on extraction behavior of different coatings
      for VFAs and the chromatographic behavior of VFAs in a Stabilwax-DA capillary
      column (30 mx0.32 mm i.d., 0.25 microm film thickness) using nitrogen as carrier
      gas, the polyacrylate fiber is selected as the satisfactory coating for VFAs
      analysis, and optimum chromatographic conditions are obtained. The oven
      temperature is programmed at 70 degrees C for 2 min, then a 4 degrees C/min rate
      until 180 degrees C, holding 2 min, and then a 20 degrees C/min rate until 200
      degrees C, holding the final temperature for 3 min. The various parameters
      including extraction time, extraction temperature, pH value, ion strength, sample
      volume, and desorption conditions are investigated for the optimization of HS
      SPME performance for VFAs in the wastewater. The experimental results show that
      the linear dynamic ranges are 10-45000 microg/L, and over two to four orders of
      magnitude depending on different acids. The detection limit (3sigma) for VFAs are
      low to microg/L levels and the relative standard deviations are less than 10%,
      and the recoveries are between 85% and 117%. By using 2-ethylbutyric acid as
      internal standard, the proposed method is successfully applied to the
      determination of VFAs in wastewater from the constructed wetlands.

PMID- 18718132
TI  - Pesticide levels in ground and surface waters of Primavera do Leste Region, Mato
      Grosso, Brazil.
AB  - Residues of the herbicides simazine, metribuzin, metolachlor, trifluralin,
      atrazine, and two metabolites of atrazine, deisopropylatrazine (DIA) and
      deethylatrazine (DEA), are surveyed in the surface and groundwater of the
      Primavera do Leste region, Mato Grosso, Brazil during September and December 1998
      and April 1999. Different water source sampling stations of groundwater
      (irrigation water well, drinking water well, and water hole) and surface water
      (dam and river) are set up based on agricultural land use. A solid-phase
      extraction procedure followed by gas chromatography-nitrogen-phosphorus detection
      is used for the determination of these compounds. All compounds are detected at
      least once in water samples. A temporal trend of pesticide contamination is
      observed, with the highest contamination frequency occurring in December during
      the main application season. Metribuzin shows the highest individual detection
      frequencies throughout the monitoring period, followed by metolachlor, simazine,
      and DEA. The maximum mean concentrations of pesticides in this study are in the
      range from 0.14 to 1.7 microg/L. We deduct that the contamination of water
      resources is predominantly caused by non-point pollution of pesticides used in
      intensive cash-crop cultures of the Cerrado area. Therefore, a continuous
      monitoring of pesticide concentrations in water resources of this tropical region
      is necessary to detect the longer term contamination trends and developing health
      risks.

PMID- 18718133
TI  - Development of a size exclusion chromatography-electrochemical detection method
      for the analysis of total organic and inorganic chloramines.
AB  - A size exclusion chromatography (SEC) followed by post-column reaction with
      iodide and electrochemical detection method is developed for analysis of total
      organic and inorganic chloramines. Ammonium chloride and a group of test
      compounds (Glycine, Tyrosine, DL-Alanyl-DL-Alanine, Arg-Gly-Asp-Ser, Bradykinin,
      Aprotinin, and alpha-Lactalbumin) are selected and chlorinated to represent
      inorganic chloramines and different sizes of organic N-chloramines. An analytical
      SEC column with pore size of 60A is used and chromatographic conditions including
      the working electrode potential and flow rate are optimized to gain optimum
      resolution and sensitivity. The detection limits are estimated to be 0.12 mg/L
      and 0.05 mg/L, respectively, for tested inorganic and organic chloramines.

PMID- 18718134
TI  - A chemometric strategy for optimization of solid-phase microextraction:
      determination of bisphenol A and 4-nonylphenol with HPLC.
AB  - A sensitive method for the analysis of bisphenol A and 4-nonylphenol is developed
      by means of the optimization of solid-phase microextraction using Uniform
      Experimental Design methodology followed by high-performance liquid
      chromatographic analysis with fluorescence detection. The optimal extraction
      conditions are determined based on the relationship between parameters and the
      peak area. The curve calibration plots are linear (r2>or=0.9980) over the
      concentration range of 1.25-125 ng/mL for bisphenol A and 2.59-202.96 ng/mL for 4
      nonylphenol, respectively. The detection limits, based on a signal-to-noise ratio
      of 3, are 0.097 ng/mL for bisphenol A and 0.27 ng/mL for 4-nonylphenol,
      respectively. The validity of the proposed method is demonstrated by the analysis
      of the investigated analytes in real water samples and sensitivity of the
      optimized method is verified by comparing results with those obtained by previous
      methods using the same commercial solid-phase microextraction fiber.

PMID- 18718136
TI  - Enhanced extraction of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) and
      hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in the presence of sodium dodecyl
      sulphate and its application to environmental samples.
AB  - A method for enhanced extraction of octahydro-1,3,5,7-tetranitro-1,3,5,7
      tetrazocine (HMX) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) from
      environmental samples is developed with the assistance of sodium dodecyl sulphate
      (SDS) surfactant. In this study, the concentration of SDS surfactant and other
      analytical parameters are optimized on a high-performance liquid chromatography
      UV system. An isocratic flow of 1.0 mL/min with mobile phase acetonitrile-water;
      70:30 (v/v) at 230 nm wavelength on a reverse-phase amide column is used for
      baseline separation of explosives and making calibration curves. The amount of
      recovered explosives from spiked soil and water samples are calculated. The
      limits of detection obtained for HMX and RDX standards are 1.5 and 3.8 ppb
      (S/N=3), respectively, which are much better than obtained by the Environmental
      Protection Agency method 8330. The recoveries are found to be enhanced by 1.7 and
      1.6-fold with SDS solution as compared to water for HMX and RDX, respectively,
      from soil samples.

PMID- 18718135
TI  - Studies of human and veterinary drugs' fate in environmental solid samples-
      analytical problems.
AB  - The improvement of medical care worldwide is one of the reasons for the
      increasing production of pharmaceutical products. Human medicines are affordable
      to a greater proportion of the world's population. But a significant amount of
      used pharmaceuticals can create problems--accessibility to high volume production
      pharmaceuticals contributes to an increased contamination in the environment and
      the possibility of adverse effects on humans and animals. Many of these
      substances and their metabolites end up in the soil, sediments, and sludge.
      Knowledge regarding the environmental occurrence of pharmaceutical products is
      increasing, but information in the peer-reviewed literature regarding the fate
      and effects of most pharmaceuticals is limited. One of the reasons for this lack
      of data is that, until now, there have been few analytical methods capable of
      detecting these compounds at the low levels, which might be expected in the
      environment. This review article covers recent developments in the analysis of
      pharmaceuticals in environmental solid matrices (including soil, sediments, and
      sludge). We will report applications of different solid sample extraction
      methods, and current advances in liquid chromatography coupled with mass
      spectrometry for detection and identification of selected drugs in sludge, soils,
      manure, and sediments.

PMID- 18718137
TI  - Analysis of phenoxyl-type N-methylcarbamate pesticide residues in vegetables by
      capillary zone electrophoresis with pre-column hydrolysis and amperometric
      detection.
AB  - With systematic studies of pre-column thermalhydrolysis, a method is described
      for the determination of fivephenoxyl-type N-methylcarbamates (NMCs) (viz.,
      propoxur, carbofuran, 3-hydroxy-carbofuran, carbaryl, and bendiocarb) in
      vegetables by capillary zone electrophoresis with amperometric detection. Effects
      of hydrolysis parameters such as alkali medium, temperature, and hydrolysis time,
      as well as separation conditions, are investigated. Under the optimum conditions,
      baseline separation of five hydrolysates is achieved within 16 min. Good
      calibration curves of propoxur, carbofuran, 3-hydroxy-carbofuran, carbaryl, and
      bendiocarb are obtained from 1.20x10(-7) to 5.00x10(-5) mol/L, and their
      detection limits (S/N=3) are 1.80x10(-8), 1.50x10(-8), 1.80x10(-8), 2.50x10(-8),
      and 1.80x10(-8) mol/L, respectively, which is approximately 20 approximately 50
      fold more sensitive than those previously reported with a UV method. In the
      application of vegetable samples, the five NMCs are well determined. Average
      recoveries of 75 approximately 89% and 86 approximately 100% at fortified levels
      of 0.05 and 0.80 mg/kg are achieved with relative standard deviations of 2
      approximately 6%, respectively. The method is sensitive, reproducible, and
      provides an alternative means for the analysis of phenoxyl-type NMC pesticide
      residues.

PMID- 18718138
TI  - Determination of pyrethroid pesticide residues in vegetables by solvent sublation
      followed by high-performance liquid chromatography.
AB  - A novel method is developed for separating and enriching pyrethroid pesticides
      from vegetables by solvent sublation, and determination of the pyrethroids is
      performed by high-performance liquid chromatography (HPLC). The effects of
      organic solvent, pH of the solution, nitrogen flow rate, and sublation time on
      the sublation efficiency of pyrethroids are investigated in detail, and the
      optimal conditions of the solvent sublation are selected. The floated product of
      vegetables in the optimal conditions is determined by HPLC. The limit of
      detection values range from 1.4 microg/kg (for bifenthrin) to 4.2 microg/kg (for
      fenpropathin). The recoveries of spiked vegetable samples are from 85.7% to
      110.4%, and relative standard deviation values are from 1.70% to 6.19%. The
      results are satisfactory.

PMID- 18718139
TI  - Validation and application of an HPLC method for determination of di (2
      ethylhexyl) phthalate and mono (2-ethylhexyl) phthalate in liver samples.
AB  - A reversed-phase gradient elution, UV detection method is developed for the
      simultaneous determination of mono (2-ethylhexyl) phthalate [MEHP] and di (2
      ethylhexyl) phthalate [DEHP] in tissue samples. The method is validated with
      respect to extraction recovery, inter and intra-day precision, linearity of
      response, detect ability, and specificity. The validated method has been
      successfully applied to the study of DEHP and MEHP in liver, kidney, testis,
      brain, and plasma samples from rat.

PMID- 18718140
TI  - A method for the low-level (ng/g) determination of perfluorooctanoate in carpet
      by LC-MS-MS using matrix extracted standards.
AB  - Fluorotelomer-based acrylic polymers are applied to the surface of carpet to
      impart oil, stain, and water repellence properties. Concerns that fluorotelomer
      based polymers are a possible source of "low level" exposure to humans, coupled
      with their widespread use have prompted the need to develop a method to detect
      and measure perfluorooctanoate (PFO) in carpet. A liquid chromatography tandem
      mass spectrometry method for the determination of PFO in carpet using a dual
      labeled 13C-perfluoroctanoic acid (13C-PFOA) internal standard is successfully
      developed and validated. Levels of PFO are determined using a gradient, reversed
      phase high-performance liquid chromatography (HPLC) method with acetic acid
      acidified water-methanol, separated on a 50 mm Phenomenex Synergi Polar RP
      column. Ions monitored are 413 (parent) and 369 (daughter) for PFO and 415
      (parent) and 370 (daughter) for dual labeled 13C-PFOA internal standard. Accuracy
      and precision over three days for 5 to 900 ng/g PFO in carpet ranged from 2.4% to
      7.6% and 3.7% to 14.1%, respectively. Overall extraction efficiency for samples
      (n=30) fortified with 13C-PFOA at 20 ng/g and perfluorooctanoic acid (PFOA) at 5,
      50, and 500 ng/g is 98.9%+/-8.1%. Specificity of the method was evaluated with
      two different carpet samples.

PMID- 18718141
TI  - Determination of residual isobutylene oxide--a genotoxic starting material in a
      drug substance by static headspace gas chromatography.
AB  - A sensitive static headspace gas chromatography (sHS-GC) method is developed and
      validated for the determination of residual isobutylene oxide (IBO)-a genotoxic
      starting material in a drug substance for Phase I clinical trial studies. The
      experimental parameters, such as headspace vial pressure, headspace oven
      temperature, vial equilibration time, column flow rate, and GC oven temperature
      programs are optimized. Under the optimal conditions, the recovery is between
      89.3% and 102.4% for spiked samples at three levels of IBO concentration in
      triplicates in sample preparations. Limits of quantitation (LOQ) and detection
      (LOD) of the standard solutions are 0.048 and 0.018 microg/mL, respectively.
      Linear range from 0.018 to 6 microg/mL is obtained with a correlation coefficient
      of 0.9999. The method is applied to determine residual IBO in drug substance
      samples from different batches.

PMID- 18718142
TI  - Development and validation of a liquid chromatography-mass spectrometry method
      for the determination of 4,5-diazafluoren-9-one.
AB  - A new liquid chromatography-mass spectrometry (LC-MS) method is developed and
      validated for the identification and determination of novel 4,5-diazafluoren-9
      one compound. The method employs a Waters XTerra RP-18 column (150 mmx4.6 mm,
      i.d. 5 microm) with a mobile phase comprised of a (50:50, v/v) mixture of
      deionized water containing 0.2% acetic acid (solvent A) and methanol (solvent B)
      at a flow rate of 1 mL/min, at 35 degrees C. The detection is performed with
      photodiode-array (PDA) set at 210-400 nm and single quadropole mass spectrometer
      with electrospray ionization (ESI) positive ion mode. The chromatographic
      separation is achieved in less than 3 min. The linearity is established over the
      concentration range of 0.1-0.5 mg/mL (r2=1.000). The mean RSD values for intra-
      and inter-day precision studies are <2%. The recovery of 4,5-diazafluoren-9-one
      ranged between 99.84 and 99.97%. The limits of detection and quantitation are
      determined to be 0.58 and 0.1 mg/mL, respectively.

PMID- 18718143
TI  - Simultaneous determination of aceclofenac, paracetamol, and chlorzoxazone by RP
      HPLC in pharmaceutical dosage form.
AB  - A simple, rapid, and precise reversed-phase liquid chromatographic method is
      developed for simultaneous determination of paracetamol, aceclofenac, and
      chlorzoxazone in their ternary mixtures of commercial pharmaceutical preparation.
      This method uses a Zorbax SB C18, 250 x 4.6 mm, 5 microm analytical column.
      Mobile phase is acetonitrile and buffer (40:60, v/v), buffer containing 50 mM
      orthophosporic acid; pH of the buffer is adjusted to 6 with 10% w/v sodium
      hydroxide solution. The instrumental settings are at a flow rate of 1 mL/min; the
      column temperature is 25 degrees C, and detector wavelength is 270 nm. The sample
      concentrations are measured on weight basis to avoid the internal standard. The
      method is validated and shown to be linear. The correlation coefficients for
      paracetamol, aceclofenac, and chlorzoxazone are 0.9981, 0.9990, and 0.9986,
      respectively. The recovery values for paracetamol, aceclofenac, and chlorzoxazone
      ranged from 100.7-101.4%, 100.4-101.0%, and 100.5-101.3%, respectively. The
      relative standard deviation for six replicates is always less than 2%. This HPLC
      method is successfully applied to the simultaneous quantitative analysis of the
      title drugs in tablets and can be applied for assay and dissolution test of
      tablets for the estimation of paracetamol, aceclofenac, and chlorozoxazone in
      their commercial samples.

PMID- 18718144
TI  - Studies on neurosteroids XX. Liquid chromatography-tandem mass spectrometric
      method for simultaneous determination of testosterone and 5alpha
      dihydrotestosterone in rat brain and serum.
AB  - Testosterone (T) and 5alpha-dihydrotestosterone (DHT) are now referred to not
      only as androgenic steroid hormones, but also as neuroactive steroids, because
      they elicit anesthetic and anxiolytic effects. Methods using liquid
      chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS)
      coupled with derivatization are developed and validated to examine rat brain and
      serum levels of T and DHT and their stress-induced changes. The steroids are
      extracted with methanol-acetic acid from the brain tissue or serum, purified
      using solid-phase extraction cartridges, derivatized with a permanently charged
      reagent, 2-hydrazino-1-methylpyridine, and subjected to LC-MS-MS. [19,19,19
      (2)H3]-T is used as the internal standard. The intra- and inter-assay
      coefficients of variation are below 10.0%, and the analytical recoveries are 98.1
      103.0%. The developed methods are applied to the animal study and it was found
      that a fair amount of DHT is continuously and locally synthesized in the brain,
      and its level is not changed by the immobilization stress and depends on the
      brain T level.

PMID- 18718145
TI  - Gas chromatographic-mass spectrometric analysis of acrylamide and acetamide in
      cigarette mainstream smoke after on-column injection.
AB  - A method is described for the simultaneous determination of two short-chained
      amides, acrylamide and acetamide (classified by the International Agency for
      Research on Cancer as probable and possible human carcinogens, respectively), in
      total particulate matter using gas chromatography-on-column injection and mass
      spectrometric detection. Sample preparation is kept to a minimum, and the
      proposed analytical procedure proves to be fast, sensitive, and precise.
      Validation studies show good linearity with a regression coefficient of r2=.000
      for both compounds. Quantitation limits are 32 ng/mL for acrylamide and 70 ng/mL
      for acetamide. In the particulate phase of mainstream smoke from the University
      of Kentucky Reference Cigarette 2R4F, 2.3 microg/cig acrylamide and 4.7
      microg/cig acetamide are found; no acetamide and only .0074 microg/cig acrylamide
      is found in the gas phase. Possible mechanisms of formation in cigarette smoke
      are discussed.

PMID- 18718146
TI  - Vision 2020 - the right to sight.
AB  - The unprecedented partnership for onchocerciasis control that followed Merck's
      decision to donate Mectizan has inspired the formation of a global initiative for
      the elimination of all avoidable blindness by the year 2020. 'Vision 2020, the
      Right to Sight', jointly co-ordinated by the World Health Organization's
      Programme for the Prevention of Blindness and Deafness and the International
      Agency for the Prevention of Blindness, was launched in 1999. This initiative's
      three pillars are disease control, human resource development, and infrastructure
      development. Vision 2020's achievements to date include the growth of the
      partnership, to include more than 60 member organizations, the revitalization of
      prevention activities, the completion of Vision-2020 plans in 40% of all
      countries and a reduction not only of blindness caused by onchocerciasis but also
      of blindness caused by trachoma. Cataract remains the leading cause of avoidable
      blindness.

PMID- 18718147
TI  - The Mectizan Donation Program: 20 years of successful collaboration - a
      retrospective.
AB  - Merck is a global research-driven pharmaceutical company that, throughout its
      history, has devoted considerable effort to bringing its medicines, vaccines,
      expertise and experience to people in need around the world. Its primary
      responsibilities are: to discover, develop and deliver innovative medicines and
      vaccines that address major burdens of illness globally and/or address specific
      poor or vulnerable groups; to develop long-term business models that help its
      products reach as many people as possible; and to promote and participate in
      partnerships with governments, multilateral and non-governmental organizations,
      other private-sector organizations and communities, to build healthcare capacity
      and to address specific health and development challenges around the world. Merck
      believes that responding to global health challenges is a strategic and
      humanitarian necessity and that, through public-private partnerships, significant
      progress can be achieved. Twenty years ago, in October 1987, before collaboration
      between public and private sectors was common, Merck launched the Mectizan
      Donation Program (MDP) - a unique, multisectoral coalition involving Merck, the
      Mectizan Expert Committee (MEC), the Task Force for Child Survival and
      Development, the World Health Organization (WHO), the World Bank, the United
      Nations Children's Fund, national ministries of health, more than 35 non
      governmental development organizations, and thousands of local community
      healthworkers - to treat a debilitating, disfiguring and often blinding disease
      called onchocerciasis (river blindness). Through this programme, Merck made the
      commitment to donate Mectizan (ivermectin) for as long as needed and wherever
      needed, to combat this disease. Since the MDP's inception in 1987, Merck has
      donated >1800 million tablets of Mectizan, with >530 million treatments for
      onchocerciasis administered since 1987. The programme currently reaches >68
      million people in Africa, Latin American and Yemen annually, via community-based
      treatment programmes in 125,000 communities in 33 endemic countries. This 20-year
      old effort has achieved a number of notable results, including positive health
      impacts, economic benefits, strengthened health systems, and the empowerment of
      communities where the delivery and administration of Mectizan are managed. The
      MDP serves as a model for similar health programmes in the developing world and
      has also laid the foundation for the current integration efforts around
      'neglected' tropical diseases. It has also taught the world many valuable lessons
      - about how to mobilize resources to address significant health challenges - and
      has demonstrated that it is possible, through public-private partnerships, to
      deliver healthcare to long-neglected populations, despite seemingly
      insurmountable obstacles including inadequate financial and human resources, lack
      of social, economic and health infrastructures, civil unrest and political
      strife, and competing, high-priority health issues.

PMID- 18718148
TI  - The Onchocerciasis Control Programme in West Africa (OCP).
AB  - The Onchocerciasis Control Programme in West Africa (OCP) started operations in
      1975. Its main objectives were to eliminate human onchocerciasis, as a disease of
      public-health importance and an obstacle to socio-economic development, from the
      Programme area. By the end of 2002, the OCP covered 11 West African countries,
      and had introduced large-scale Mectizan (ivermectin) distribution to about 10
      million people, through the communitydirected treatment approach, with treatment
      coverages ranging from 51%-81%. Research on large-scale Mectizan use illustrated
      the importance of evidence-based results, the power of multicountry studies, the
      need for social science in community-driven endeavours and operations research,
      and the value of empowering communities as allies in disease control. The
      generous donation of Mectizan by Merck & Co., Inc., has increased general
      interest in health-related public-private partnerships and generated the momentum
      for other donations to tackle other diseases. The vector control on which the OCP
      was initially based successfully interrupted the transmission of the parasite
      causing human onchocerciasis, Onchocerca volvulus, in many areas. The
      introduction of Mectizan led to the decline in anterior-segment lesions in the
      eye and the arrest of posterior-segment lesions. The drug continues to be highly
      effective in morbidity control, although recently there have been reports of sub
      optimal responses in some adult O. volvulus, albeit in a few, very small and
      isolated foci.

PMID- 18718149
TI  - The African Programme for Onchocerciasis Control (APOC).
AB  - The African Programme for Onchocerciasis Control (APOC) was launched in 1995,
      ultimately to eliminate human onchocerciasis from the African countries in which
      the disease was endemic. This goal is being achieved, via a public-private
      partnership, using a strategy, of community-directed treatment (CDT) with
      ivermectin, that is based on the empowerment of each target community. It is
      estimated that the Programme saved 3 million disability-adjusted life-years
      between 1996 and 2005, and, with a free supply of ivermectin, this gives an
      estimated 17% economic rate of return on the cost of treatment delivery. In
      addition to the substantial direct benefits from the control of onchocerciasis,
      there are several indirect benefits, including the de-worming of children who
      receive ivermectin, increased school attendance, general improvements in
      community and individual health, and increased food production. A key component
      of the Programme is the co-implementation of onchocerciasis control with other
      health interventions that can be delivered at the community level. This approach
      has proved highly effective, leading to higher levels of therapeutic coverage for
      onchocerciasis control as well as improved delivery of other services, especially
      vaccination programmes. In the accompanying article, the outcome and challenges
      of the APOC in 2006, in 105,866 participating communities spread across 15
      countries, are described.

PMID- 18718150
TI  - Special intervention zones.
AB  - The Special Intervention Zones (SIZ) of the former Onchocerciasis Control
      Programme (OCP) were launched in December 2002, following the closure of the OCP,
      to sustain the momentum that had been gained for onchocerciasis control through
      Mectizan distribution and vector control. The donation of Mectizan in 1987 was
      fortuitous for the OCP, as vector control had become costly and ineffective in
      certain areas. Mectizan distribution benefitted the populations affected by
      onchocerciasis, who saw improvements to their health. When the SIZ were launched,
      Mectizan distribution became the primary strategy for onchocerciasis control.
      Good coverages with Mectizan mass treatments have been achieved and maintained in
      most of the SIZ, leading to dramatic reductions in both the prevalences and
      intensities of onchocercal infection. The control efforts in the SIZ in Sierra
      Leone and some areas of Ghana and Togo, however, need to be strengthened.
      Although the SIZ closed at the end of 2007, the Mectizan distributions will
      continue until 2012.

PMID- 18718151
TI  - The Onchocerciasis Elimination Program for the Americas (OEPA).
AB  - Human onchocerciasis (river blindness) occurs in 13 foci distributed among six
      countries in Latin America (Brazil, Colombia, Ecuador, Guatemala, Mexico and
      Venezuela), where about 500,000 people are considered at risk. An effort to
      eliminate the disease from the region was launched in response to a specific
      resolution adopted by the PanAmerican Health Organization (PAHO) in 1991: to
      eliminate onchocerciasis from the region, as a public-health problem, by 2007.
      The effort took advantage of the donation of the drug Mectizan (ivermectin) by
      Merck & Co., Inc. In 1992, the Onchocerciasis Elimination Program for the
      Americas (OEPA) was launched, with its headquarters in Guatemala, to act as a
      technical and co-ordinating body of a multinational, multi-agency coalition that
      includes the endemic countries, PAHO, The Carter Center, Lions Clubs, the United
      States Centers for Disease Control and Prevention, The Bill and Melinda Gates
      Foundation, Merck & Co., Inc., and other partners. This public-private
      partnership facilitated the establishment of programmes for the semi-annual mass
      administration of Mectizan in the six countries with onchocerciasis. The aims
      were to (1) provide sustained treatments, with coverage reaching at least 85% of
      those eligible to receive the drug (in the 1845 endemic communities that are
      distributed within the 13 regional foci); (2) eliminate new morbidity caused by
      Onchocerca volvulus infection by 2007; and (3) eliminate transmission of the
      parasite wherever feasible. Significant progress has already been made in all six
      countries, each of which has active programmes with treatment coverages exceeding
      the target of 85%. The progress is being documented in accordance with
      certification guidelines for onchocerciasis elimination established by the World
      Health Organization. No new cases of onchocercal blindness are being reported in
      the region, and ocular disease attributable to O. volvulus has been eliminated
      from nine of the 13 foci. Treatment is no longer needed in Santa Rosa, Guatemala,
      where transmission has been eliminated, and will be halted in at least three
      other foci in 2008, as they confirm the interruption of transmission. Treatment
      efforts should now be concentrated on the five foci where significant
      transmission remains: Central (Guatemala), Amazonas/Roraima (Brazil), North
      central (Venezuela), North-east (Venezuela) and South (Venezuela). Based upon the
      experience gained, the well-established operations and the success achieved so
      far, it seems reasonable to estimate that onchocerciasis could be eliminated from
      most of the remaining foci in the Americas by 2012. The protocol, criteria and
      deadline for stopping all onchocerciasis treatment in the region should soon be
      addressed by OEPA's Program Co-ordinating Committee (PCC), in co-ordination with
      the PAHO.

PMID- 18718152
TI  - The World Bank.
AB  - The control of human onchocerciasis (river blindness) is one of the most
      successful global partnerships ever supported by the World Bank. Mectizan mass
      treatments have greatly contributed to this success and have shaped the
      strategies of the programmes in which the World Bank has been involved - the
      Onchocerciasis Control Programme (OCP), which covered onchocerciasis control in
      West Africa until 2002, and the African Programme for Onchocerciasis Control
      (APOC), which is currently working in 30 countries, to protect millions of people
      from onchocerciasis. Through the strategy of community-directed treatment with
      ivermectin (CDTI), onchocerciasis control in Africa was transformed from a
      technologically-driven and vertical health initiative to a community-directed
      process of treatment and empowerment. Together, CDTI and the donation of Mectizan
      also reduced costs, producing one of the most effective and affordable disease
      control schemes ever seen, and the CDTI strategy is now being applied to other
      disease-control initiatives. The onchocerciasis programmes have also been
      exemplary in shaping partnerships with communities, countries, the World Health
      Organization, governments, non-governmental development organizations, and the
      private sector. The Bank's involvement in onchocerciasis control has helped
      mobilize funds, giving confidence to other donors. More than U. S.$800 million
      was raised for both the OCP and APOC (excluding the initial costs of Mectizan).
      With these funds and the commitment of the partners involved, high coverages have
      been achieved in the Mectizan distributions. The Bank is confident that, during
      the years to come, the partners will continue their success, and that the APOC
      will achieve its goals by the target date for its closure, in 2015.

PMID- 18718153
TI  - The NGDO Co-ordination Group for Onchocerciasis Control.
AB  - Since the beginning of the donation of Mectizan by Merck & Co., Inc., non
      governmental development organizations (NGDO) have been actively involved in the
      mass distribution of this drug to control onchocerciasis. In 2006, the network of
      NGDO involved in onchocerciasis control assisted in the treatment of over 62
      million people. The current strategy that is used for distribution in Africa,
      community-directed treatment with ivermectin (CDTI), is very well suited for
      integration with other health activities. NGDO have been the pioneers in
      integrating comprehensive eye care, insecticide-treated nets for malaria, the
      control of multiple 'neglected' tropical diseases, and vitamin-A supplementation.
      These expanded activities bring with them new challenges, which need to be
      addressed by all partners and where the NGDO will play an active role.

PMID- 18718154
TI  - The Mectizan Donation Program (MDP).
AB  - The launch of the Mectizan Donation Program (MDP) in 1987, by Merck & Co., Inc.,
      created a number of new opportunities for onchocerciasis control. The
      microfilaricide Mectizan was rapidly put to ?use by the Onchocerciasis Control
      Programme in West Africa (OCP), for mass treatment by field teams in selected
      areas. Other milestones in Mectizan treatment included the establishment, in
      1992, of the Onchocerciasis Elimination Program for the Americas, and the
      creation of the African Programme for Onchocerciasis Control (APOC) in 1995, the
      latter programme covering all African countries in need outside of the OCP area.
      In 1998, the donation of Mectizan was expanded to include the treatment of
      lymphatic filariasis in those African countries where that disease is co-endemic
      with onchocerciasis. In the past, the development of a broad partnership around
      the MDP played a very important role, including non-governmental development
      organizations collaborating with the ministries of health in endemic countries. A
      new community-directed treatment strategy, which made it easier to reach out to
      all those in need, including those in remote areas, was developed by the APOC in
      collaboration with the World Health Organization's Special Programme for Research
      and Training in Tropical Diseases (TDR). Several drug-management issues,
      including dosing, shelf-life, safety, and the reporting of severe adverse
      experiences, were addressed by the MDP, through its Mectizan Expert Committee,
      and by Merck & Co., Inc. A major research effort for the safe treatment of
      onchocerciasis in loiasis-endemic areas has also been supported by the MDP.
      Presently there are national programmes for Mectizan mass treatment in all 33
      endemic countries in need of such treatment; >69 million Mectizan treatments for
      onchocerciasis were provided during 2006, and this number is expected to grow to
      at least 100 million treatments/year by 2010. This achievement has resulted in
      great public-health and socio-economic benefits for the populations concerned.
      Future challenges will include additional support to 'fragile states' resulting
      from conflicts or natural disasters, and the need for a strengthened primary
      healthcare (PHC) infrastructure. The community-directed-treatment approach has
      been a great success but there is still a need to link the treatments to PHC, for
      the long-term sustainability of the treatments. The presence of loiasis in vast
      areas of Central Africa imposes a need for the mapping of that disease, and the
      application of safety precautions when distributing Mectizan in those areas. The
      recent decision to extend the APOC up to 2015 should facilitate the building of
      sustainable Mectizan treatment programmes that are integrated with the control of
      other neglected tropical diseases, such as lymphatic filariasis, intestinal
      helminths and trachoma. It will be important to define the safe end-point for
      Mectizan treatment in various settings, and an ongoing study by TDR will address
      this issue. There is also a need to consider the application of more frequent
      Mectizan treatments, possibly with adjunct measures, such as ground-based vector
      control in selected areas, or new chemotherapeutic approaches (as and when they
      become available).

PMID- 18718155
TI  - Regulating primary care: regulation as the guardian of quality.

PMID- 18718156
TI  - Professional regulation in primary care: the long road to quality improvement.

PMID- 18718157
TI  - Joining up the dots of patient safety.

PMID- 18718158
TI  - The practice and regulation of non-medical healthcare professionals in community
      based and primary care: maintaining old landscapes or encouraging creativity?

PMID- 18718159
TI  - Professional regulation in primary care: improving quality and safety ... we
      hope.

PMID- 18718160
TI  - Understanding risk and safety in home health care: the limits of generic
      frameworks.
AB  - BACKGROUND: Patient safety and adverse events in primary care are receiving
      increasing attention from policy makers, professional bodies and researchers.
      Various taxonomic models have been developed to specify the factors that
      predispose to adverse events in hospital settings. These are assumed to have
      general applicability across different healthcare settings. However, they have
      never been applied to home health care. AIMS: This study helps define the value
      of one such model in a domiciliary setting. The principal purpose of the study
      was to understand the circumstances in which the involvement of local authority
      funded home carers as well as NHS-funded district nurses in medication-related
      activities for older people living at home in the UK might jeopardise patient
      safety. METHOD: The study was undertaken in two contrasting sites. One was in
      London and the other in the Midlands. District nurses and home carers were
      purposively selected to take part in semi-structured interviews. The data were
      used to construct a taxonomic model that specified the factors that predispose
      older people to adverse events when medication-related responsibilities are
      transferred from district nursing to home care services. RESULTS: The new
      taxonomy was compared to the taxonomic model under investigation. Dissonance
      existed within a number of categories. CONCLUSIONS: The model under investigation
      was found to be too narrow for application in domiciliary settings. The
      challenges that exist in home health care are often very different from those
      that exist in hospital settings, from which the model under investigation was
      derived. The root causes of accidents are most likely to be identified by models
      empirically derived from, and tailored to fit, the particular circumstances in
      which they are to be applied.

PMID- 18718161
TI  - Networks of primary and secondary care services: how to organise services so as
      to promote efficiency and quality in access while reducing costs.
AB  - Governments in countries with national health systems have been concerned with
      how to organise services so as to achieve improvements in efficiency and quality
      in healthcare delivery, as well as to control costs. In this study, a stochastic
      discrete event simulation model to study the organisation of primary and
      secondary care services is proposed. The model was built with reference to the
      context of the Portuguese NHS, was implemented in the Simul8 software program and
      was applied to the Portuguese Setubal healthcare subregion (SHCR). For its
      application, a database with 2005 production, resource and cost indicators was
      built to calibrate and validate the applied model. After validation, three
      different policy scenarios were tested: the first one concerning a 10% increase
      in demand for primary care services; the second considering a shift between
      specialists and generalist physicians; and a third regarding restructuring of
      primary care services. Results show that although the current system is not
      prepared to cope with a rise in demand, the other scenarios indicate that there
      is room for primary care reforms to increase the system's efficiency and
      accessibility, while lowering total costs.

PMID- 18718162
TI  - The future shape of healthcare regulation and the role of lay members.
AB  - Moi Ali looks at soon-to-be-implemented legislative changes that will alter the
      way members of healthcare regulators are selected, and offers a personal view on
      the benefits these changes will bring.

PMID- 18718163
TI  - Is there a need for professional regulation for primary care mental health
      workers?
AB  - Primary care mental health (PCMH) workers need not have a professional
      qualification. The development of the role of these workers highlights the
      influence of a number of factors that provide a framework that offers assurance
      of the protection of the public and the promotion of quality of care. Factors
      such as legislation, codes of practice, stringent recruitment procedures,
      clinical supervision, employing evidence-based practice, and training all play an
      equal part in determining safe and good practice. Together, these factors
      formulate standards of practice which limit the need for professional regulation.
      The training of PCMH workers is guided by a national curriculum and other
      requirements. Practice of these workers is governed by various legislative
      frameworks and guidance. The requirement for clinical supervision for PCMH
      workers is a crucial element in promoting safe and effective care. In addition,
      stringent recruitment procedures ensure unsuitable candidates are not selected
      for the positions. This paper argues that professional regulation is not needed
      as there are other systems with similar significance that promote quality of care
      and can offer protection to the public.

PMID- 18718164
TI  - The health of a nation: perspectives from Cuba's national health system.
AB  - This paper focuses on the current healthcare system in Cuba and provides a
      description of an alternative healthcare provision. The information is based on a
      visit to the country in 2007 as a member of a health study tour. The purpose of
      the visit was to explore the functioning of a population-based health service and
      to interview key people. The data are compared with the literature on Cuba. The
      effects of the economic crisis, the US embargo and the absence of international
      debate about Cuba's health achievements are discussed.

PMID- 18718165
TI  - Management of chronic kidney disease in primary health care: position paper of
      the European Forum for Primary Care.

PMID- 18718166
TI  - Web alert: resources to support the development of a knowledge management
      strategy.

PMID- 18718167
TI  - Valproic acid-mediated transcriptional regulation of human GM3 synthase (hST3Gal
      V) in SK-N-BE(2)-C human neuroblastoma cells.
AB  - AIM: To investigate whether valproic acid (VPA) modulates human GM3 synthase
      (hST3Gal V) mRNA expression, as a part of ganglioside GM3 biosynthesis, in human
      neuroblastoma cells. METHODS: Using RT-PCR and immunofluorescent confocal
      microscopy, we examined hST3Gal V mRNA and GM3 levels during VPA-induced
      differentiation of human neuroblastoma SK-N-BE(2)-C cells. We characterized the
      VPA-inducible promoter region within the hST3- Gal V gene using luciferase
      constructs carrying 5'-deletions of the hST3Gal V promoter. RESULTS: RT-PCR
      indicated that VPA-mediated hST3Gal V induction is transcriptionally regulated.
      Functional analysis of the 5'-flanking region of the hST3Gal V gene demonstrated
      that the -177 to -83 region, which contains a cAMP-responsive element (CRE) at 
      143, functions as the VPA-inducible promoter by actively binding CRE binding
      protein (CREB). In addition, sitedirected mutagenesis and electrophoretic
      mobility shift assay indicated that the CRE at -143 is crucial for the VPA
      induced expression of hST3Gal V in SK-NBE( 2)-C cells. CONCLUSION: Our results
      isolated the core promoter region in the hST3Gal V promoter, a CRE at -143, and
      demonstrated that it is essential for transcriptional activation of hST3Gal V in
      VPA-induced SK-N-BE(2)-C cells. Subsequent CREB binding to this CRE mediates VPA
      dependent upregulation of hST3Gal V gene expression.

PMID- 18718168
TI  - Wuweizisu C from Schisandra chinensis decreases membrane potential in C6 glioma
      cells.
AB  - AIM: To study the effects of dibenzocyclooctadiene lignans isolated from
      Schisandra chinensis, such as wuweizisu C, gomisin N, gomisin A, and schisandrin,
      on the membrane potential in C6 glioma cells. METHODS: The membrane potential was
      estimated by measuring the fluorescence change in DiBAC-loaded glioma cells.
      RESULTS: Wuweizisu C decreased the membrane potential in a concentration
      dependent manner. Gomisin N and gomisin A, however, showed differential
      modulation and no change was induced by schisandrin or dimethyl- 4,4'-dimethoxy
      5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate, a synthetic drug derived
      from dibenzocyclooctadiene lignans. We found no involvement of G(i/o ) proteins,
      phospholipase C, and extracellular Na(+) on the wuweizisu C-induced decrease of
      the membrane potential. Wuweizisu C by itself did not change the intracellular
      Ca(2+)[Ca(2+)](i) concentration, but decreased the ATP-induced Ca(2+) increase in
      C6 glioma cells. The 4 lignans at all concentrations used in this study did not
      induce any effect on cell viability. Furthermore, we found a similar decrease of
      the membrane potential by wuweizisu C in PC12 neuronal cells. CONCLUSION: Our
      results suggest that the decrease in the membrane potential and the modulation of
      [Ca(2+)](i) concentration by wuweizisu C could be important action mechanisms of
      wuweizisu C.

PMID- 18718169
TI  - Osteogenic-related gene expression profiles of human dental follicle cells
      induced by dexamethasone.
AB  - AIM: Human dental follicle cells (hDFC) have the ability to differentiate into
      mineralized tissue-forming cells during root and periodontal development or
      osteogenic induction in vitro. The present study aimed to validate the osteogenic
      induction of hDFC by dexamethasone (DEX) and to explore the changes of related
      genes responsible for the osteogenic differentiation process. METHODS: Passage
      cultured hDFC were induced by DEX and analyzed for mineralization activity by
      morphological observation, alkaline phosphatase (ALP) activity, and alizarin red
      S staining. GEArray Q series human osteogenesis gene array was used to describe
      large-scale gene expression in treated hDFC compared to the control group.
      Quantitative real-time RT-PCR was performed to confirm the microarray data by
      analyzing the expression of 7 critical transcripts. RESULTS: Osteogenic
      differentiation of hDFC was confirmed by morphological change, elevated ALP
      activity and calcified nodules. In 96 genes investigated through the microarray
      analysis, 20 genes were upregulated and 8 genes were downregulated more than 2
      fold. The results of the real-time RT-PCR correlated with the microarray
      analysis. The expression of the transforming growth factor-beta superfamily
      showed varying degrees of increase, and fibroblast growth factors exhibited a
      differential changing trend of expression. The expression of most types of
      collagen genes representative of extracellular matrixes increased under DEX
      treatment while small mothers against decapentaplegic 6 and 7 expressions
      significantly decreased. CONCLUSION: Our results demonstrated that hDFC displayed
      osteoblastic features in both phenotypic and genotypic traits induced by DEX in
      vitro.

PMID- 18718170
TI  - Subconjunctival sustained release 5-fluorouracil for glaucoma filtration surgery.
AB  - AIM: To determine the release characteristics of a 5-fluorouracil-loaded poly
      (lactic acid) disc (5-FU-PLA-DS) and the effect of sustained drug delivery on the
      success of glaucoma filtration surgery in rabbit eyes. METHODS: A method of
      microspheres accumulated by excessive carriers was used in the preparation of the
      5-FU-PLA-DS. The disc was characterized for drug loading, entrapment efficiency,
      in vitro release, and external morphology. It was then implanted
      subconjunctivally into rabbit eyes with trabeculectomy. Intraocular pressure,
      ocular inflammatory reaction, filtration bleb appearance, and persistence were
      evaluated up to postoperative d 90. A quantitative analysis of 5-fluorouracil (5
      FU) was performed in the aqueous humor. Ultrasound biomicroscopy was used to
      assess the appearance of the filtering fistula. RESULTS: The 5-FU-PLA-DS was
      produced with the drug-loading of 3.07+/-0.08 mg (mean+/-SD). 5-FU was released
      for 91 d with suppressive concentrations. The decrease in intraocular pressure
      from baseline was significantly more marked in the 5-FU-PLA-DSimplanted eyes
      during postoperative d 3-90, and the persistence of bleb and filtration fistula
      was longer than the control eyes (P<0.05). Corneal toxicity and hyperemia
      triggered by 5-FU was lower in the 5-FU-PLA-DS-implanted eyes than those exposed
      to 5-FU intraoperatively. The 5-FU concentration in the aqueous humor was
      insufficient for corneal endothelial damage. No evidence of toxic reaction was
      found in the conjunctival biopsy. CONCLUSION: 5-FU-PLADS displaying sustained
      intraocular release of 5-FU, reduced intraocular pressure, and prolonged bleb
      persistence, while significantly reducing 5-FU toxicity.

PMID- 18718171
TI  - Differentiations of transplanted mouse spermatogonial stem cells in the adult
      mouse renal parenchyma in vivo.
AB  - AIM: Spermatogonial stem cells can initiate the process of cellular
      differentiation to generate mature spermatozoa, but whether it possess the
      characteristic of pluripotency and plasticity, similar to embryonic stem cells,
      has not been elucidated. This study was designed to evaluate the differentiation
      potential of spermatogonial stem cells into renal cells in vivo. METHODS:
      Neonatal mouse spermatogonial stem cells were transplanted into mature male mice
      lacking endogenous spermatogenesis. The restoration of fertility in recipient
      males was observed. Spermatogonial stem cells were then injected into renal
      parenchyma of mature female mice to make a new extracellular environment for
      differentiation. Fluorescence in situ hybridization technology (FISH) was used to
      detect the expression of chromosome Y in recipient renal tissues. To determine
      the type of cells differentiated from spermatogonial stem cells, the expression
      of ricinus communis agglutinin, vimentin, CD45, and F(4/80) proteins were
      examined in the renal tissues by immunohistochemistry. RESULTS: The proliferation
      of seminiferous epithelial cells was distinctly observed in seminiferous tubules
      of transplanted testes, whereas no regeneration of spermatogenesis was observed
      in non-transplanted control testes. In transplanted female renal tissues, FISH
      showed a much stronger immuno-fluorescence signal of chromosome Y in the
      nucleolus of epithelial cells of the renal tubule and podocytes of the
      glomerulus. CONCLUSION: The spermatogonial stem cells were successfully purified
      from mouse testicles. This finding demonstrated that spermatogonial stem cells
      could not only restore damaged spermatogenesis, but were also capable of
      differentiating into mature renal parenchyma cells in vivo.

PMID- 18718172
TI  - All-trans retinoic acid inhibits the increases in fibronectin and PAI-1 induced
      by TGF-beta1 and Ang II in rat mesangial cells.
AB  - AIM: To investigate the effect of all-trans RA (atRA) on the increases in
      plasminogen activator inhibitor-1 (PAI-1) and fibronectin that are induced by
      transforming growth factor-beta1 (TGF-beta1) and angiotensin II (Ang II) in
      cultured rat glomerular mesangial cells. METHODS: Subconfluent glomerular
      mesangial cells were serum-starved for 48 h and pretreated with atRA with
      subsequent stimulation of TGF-beta1 and Ang II. Protein expressions of cell
      associated fibronectin and PAI-1 in glomerular mesangial cells were evaluated by
      Western blot analysis. mRNA expression of RA receptors in glomerular mesangial
      cells was examined by RT-PCR. RESULTS: Retinoic acid receptor-alpha, -gamma (RAR
      alpha, -gamma) and retinoid X receptor-alpha, -beta, -gamma (RXR-alpha, -beta, 
      gamma) mRNA were expressed in rat glomerular mesangial cells. atRA pretreatment
      effectively reduced fibronectin expression in glomerular mesangial cells
      stimulated with TGF-beta 1 or Ang II for 48 h. TGF-beta 1 stimulated PAI-1
      expression reached a maximum at 5 h. atRA didn't affect the early (5 h) PAI-1
      induction by TGF-beta 1, but markedly attenuated the sustained (48 h) PAI-1
      induction. atRA also decreased the prolonged effect of Ang II on PAI-1
      expression. CONCLUSION: These results indicate that atRA inhibits the increases
      in fibronectin that are induced by TGF-beta1 and Ang II in cultured glomerular
      mesangial cells. The data also suggest that this effect of atRA is associated
      with a change in PAI-1 levels.

PMID- 18718173
TI  - Ginkgo biloba extract prevents against apoptosis induced by high glucose in human
      lens epithelial cells.
AB  - AIM: To investigate the protective effects of Ginkgo biloba extract (GBE) on high
      glucose-induced apoptosis of human lens epithelial cells (HLEC) and the possible
      molecular mechanisms. METHODS: The cultured HLEC were allotted into 6 groups:
      normal group, high glucose group, low-, moderate-, and high-dose GBE group, and
      the bendazac lysine group. Cell viability, cell apoptosis, the activities of cell
      antioxidases, aldose reductase, caspase-3, the levels of cell antioxidants, and
      the expressions of Bcl-2 and Bax were assessed by different methods. RESULTS:
      After being incubated with high glucose for 24 h, HLEC underwent apoptosis and
      exhibited significant oxidative stress. In the presence of GBE at different
      doses, the rate of HLEC apoptosis was lower and the oxidative stress state was
      significantly ameliorated. The increased ratio of Bax to Bcl-2 was significantly
      reduced and the activation of caspase-3 was suppressed by GBE in a dose-dependent
      manner. CONCLUSION: GBE prevents HLEC from high glucose-induced apoptosis through
      inhibiting oxidative stress, reducing the ratio of Bax to Bcl-2, and decreasing
      the activity of caspase-3. Therefore, GBE has a potential protective effect
      against diabetic cataract formation.

PMID- 18718174
TI  - Felodipine attenuates vascular inflammation in a fructose-induced rat model of
      metabolic syndrome via the inhibition of NF-kappaB activation.
AB  - AIM: Metabolic syndrome is associated with an increased incidence of
      atherosclerosis. Clinical studies have shown that calcium channel blockers (CCB)
      inhibit the progression of atherosclerosis. However, the underlying mechanism is
      unclear. We investigated the inhibitory effect of felodipine on adhesion
      molecular expression and macrophage infiltration in the aorta of high fructose
      fed rats (FFR). METHODS: Male Wistar rats were given 10% fructose in drinking
      water. After 32 weeks of high fructose feeding, they were treated with felodipine
      (5 mg x kg(-1) x d(-1)) for 6 weeks. The control rats were given a normal diet
      and water. The aortic expression of intercellular adhesion molecule-1 (ICAM-1)
      and vascular cell adhesion molecule-1 (VCAM-1) and the infiltration of
      macrophages were measured by real-time RT-PCR and/or immunohistochemistry. NF
      kappaB activity was measured by electrophoretic mobility shift assay (EMSA).
      RESULTS: After 32 weeks of high fructose feeding, FFR displayed increased body
      weight, systolic blood pressure (SBP), serum insulin, and triglycerides when
      compared with the control rats. The aortic expressions of ICAM-1 and VCAM-1 were
      significantly increased in FFR than in the control rats and accompanied by the
      increased activity of NF-kappaB. FFR also showed significantly increased CD68-
      positive macrophages in the aortic wall. After treatment with felodipine, SBP,
      serum insulin, and the homeostasis model assessment decreased significantly. In
      addition to reducing ICAM-1 and VCAM-1, felodipine decreased macrophages in the
      aortic wall. EMSA revealed that felodipine inhibited NF-kappaB activation in FFR.
      CONCLUSION: Felodipine inhibited vessel wall inflammation. The inhibition of NF
      kappaB may be involved in the modulation of vascular inflammatory response by CCB
      in metabolic syndrome.

PMID- 18718175
TI  - A novel anti-cancer effect of genistein: reversal of epithelial mesenchymal
      transition in prostate cancer cells.
AB  - AIM: The aim of the present study was to investigate whether low dose genistein
      affects the invasion and epithelial mesenchymal transition (EMT) of prostate
      cancer (PCa) cells. METHODS: Human PCa cell lines, IA8-ARCaP and LNCaP/ HIF-1a,
      were used in this study. The cell lines were found to process EMT in our previous
      study. The PCa cells were treated with increasing concentrations, from 0.1 to 75
      micromol/L. Proliferation was assessed with 3-(4,5-dimethylthiazol- 2-yl)-2,5
      diphenyltetrazolium bromide assay. EMT was proven by cell morphological
      transition and the expression changes of EMT-related markers, which were
      confirmed by RT-PCR, Western blotting, and indirect immunofluorescence labeling.
      Transwell invasion assay was used to analyze the invasive potency. RESULTS: The
      addition of genistein to the medium reduced the IA8-ARCaP and LNCaP/HIF-1a viable
      cell number in a dose-dependent manner (with increasing concentrations from 15 to
      75 micromol/L). Less than 15 micromol/L genistein was selected as the low dose
      concentration, which did not affect cell proliferation. The treatment of cells
      with low-dose genistein induced the reversal of EMT, which was confirmed by cell
      morphological transition and the expression changes of EMT-related markers. The
      reversal of EMT in the PCa cells by low-dose genistein was in a dose-dependent
      manner. Moreover, low-dose genistein effectively inhibited invasion of the PCa
      cells in vitro. CONCLUSION: These results showed that treatment with low-dose
      genistein may be a potential strategy for the suppression of invasive growth
      through the reversal of EMT in cancer cells, which justifies the potential use of
      soybean foods as a practical chemopreventive approach for patients with PCa.

PMID- 18718176
TI  - Protein tyrosine kinase, JNK, and ERK involvement in pseudolaric acid B-induced
      apoptosis of human breast cancer MCF-7 cells.
AB  - AIM: To investigate the apoptotic mechanism of pseudolaric acid B (PAB) in human
      breast cancer MCF-7 cells. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide analysis and morphological changes were applied to
      detect apoptosis. The percentage of apoptotic and necrotic cells were calculated
      by the lactate dehydrogenase activity-based cytotoxicity assay, and the protein
      expression was examined by Western blot analysis. RESULTS: PAB and/or the mitogen
      activated protein kinases, including p38, c-Jun-N-terminal kinase (JNK) and
      extracellular signal-regulated kinase (ERK), did not participate in necrosis. P38
      had no obvious function on apoptosis after 4 micromol/L PAB treatment for 36 h,
      but PAB induced JNK phosphorylation and inhibited ERK phosphorylation in the
      apoptotic process. In this study the inhibitor of protein tyrosine kinase (PTK)
      genistein inverted the inhibitory effect of PAB, instead promoting the survival
      of MCF-7 cells. Like genistein, another PTK inhibitor AG1024 had a similar effect
      on PAB-treated MCF-7 cells, indicating that PAB activated PTK to induce
      apoptosis. Together with PAB, genistein increased the expression of p-ERK, and
      decreased the expressions of JNK and p-JNK in PAB-treated MCF-7 cells at 36 h.
      And it is considered that the p-ERK and p-JNK were active patterns of ERK and
      JNK, respectively. CONCLUSION: PTK were upstream of ERK and JNK, and PTK induced
      apoptosis through activating JNK and inactivating ERK in PAB-treated MCF-7 cells.

PMID- 18718177
TI  - Pharmacokinetic and pharmacodynamic study of LFA3Ig fusion protein in healthy
      volunteers and patients with psoriasis.
AB  - AIM: To evaluate the pharmacokinetics (PK) and pharmacodynamics of the LFA3Ig
      fusion protein (LFA3IgFP) in healthy volunteers and patients with chronic plaque
      psoriasis. METHODS: The clinical trials included 2 phase I open studies. Study 1
      was an open-label dose escalation study in 24 healthy volunteers, and study 2 was
      a single-group, open-label study in 12 patients with chronic plaque psoriasis.
      The serum drug concentrations were measured, and the concentration-time data were
      analyzed by compartmental analysis using the Practical Pharmacokinetic Program.
      RESULTS: In study 1, after intramuscular (im) administration at a dosage of 5,
      15, and 25 mg, the concentration-time curves of LFA3IgFP fitted well to a 1
      compartment open model. Areas under the concentration-time curves increased
      linearly with dose. Clearance rates (Cls/ F) and elimination half-lives (T1/2ke)
      had no significant difference between different dose groups. A transient, slight
      decline of CD(4+) and CD(8+) T-cell subsets was observed after administration. In
      study 2, after im administration at a dosage of 15 mg weekly for 8 weeks, the
      concentration-time curve was best fitted to a 1 compartment open model, with a
      T(1/2ke ) of 307.9+/-32.7 h. The steady state was attained after the fifth
      administration. CONCLUSION: The PK behaviors of LFA3IgFP in healthy volunteers
      and patients with chronic plaque psoriasis complied with linear kinetics within
      the examined dose range. A significant accumulation was observed after repeated
      administration at a dose of 15 mg weekly for 8 weeks.

PMID- 18718178
TI  - Development and evaluation of lipid nanoparticles for camptothecin delivery: a
      comparison of solid lipid nanoparticles, nanostructured lipid carriers, and lipid
      emulsion.
AB  - AIM: Camptothecin is an anticancer drug that acts against a broad spectrum of
      tumors. The clinical application of camptothecin is limited by its insolubility,
      instability, and toxicity problems. The aim of this study was to develop and
      characterize lipid nanoparticles with different lipid cores which can circumvent
      these problems. METHODS: Lipid nanoparticles made of Precirol (solid lipid
      nanoparticles; SLN-P), Compritol (SLN-C), Precirol+squalene (nanostructured lipid
      carriers; NLC), and squalene (a lipid emulsion; LE) as the lipid core material
      were prepared. These systems were assessed and compared by evaluating the mean
      diameter, surface charge, molecular environment, camptothecin release, and cell
      viability against a melanoma. The safety and storage stability of these systems
      were also preliminarily examined. RESULTS: The particle size ranged from 190 to
      310 nm, with the NLC and LE showing the smallest and largest sizes, respectively.
      The in vitro drug release occurred in a sustained manner in decreasing order as
      follows: LE> NLC> SLN-P> SLN-C. It was found that varying the type of inner phase
      had profound effects on cell viability. The SLN-P generally showed higher
      cytotoxicity than the free control. The treatment of melanomas with the
      camptothecin-loaded SLN-C and NLC yielded cytotoxicity comparable to that of the
      free form. The percentage of erythrocyte hemolysis by all nanoparticles was < or
      =5%, suggesting a good tolerance to lipid nanoparticles. CONCLUSION: The results
      collectively suggest that the SLN-P may have the potential to serve as a delivery
      system for parenteral camptothecin administration because of the sustained drug
      release, strong cytotoxicity, limited hemolysis, and good storage stability.

PMID- 18718179
TI  - Comparison of the pharmacological effects of Panax ginseng and Panax
      quinquefolium.
AB  - Medical application of Panax ginseng was first found in "Shen-Nong Herbal
      Classic"around 200 AD Panax quinquefolium was first introduced in "Essential of
      Materia Medica" in 1694 in China. The most important bioactive components
      contained in P ginseng and P quinquefolium are ginseng saponins (GS). The
      contents of ginsenoside Rb1, Re, and Rd in P quinquefolium are higher than they
      are in P ginseng. In P ginseng, the contents of Rg1,Rb2, and Rc are higher than
      they are in P quinquefolium. P ginseng had a higher ratio of Rg1: Rb1, and which
      was lower in P quinquefolium. After steaming for several hours, the total GS will
      decrease. However, some ginsenosides (Rg2, 20R-Rg2, Rg3, Rh1 and Rh2) increase,
      while others (Rb1, Rb2, Rb3, Rc, Rd, Re, and Rg1) decrease. However, variation,
      especially in P quinquefolium, is high. P ginseng and P quinquefolium are general
      tonics and adaptogens. Rg1 and Rb1 enhance central nervous system (CNS)
      activities, but the effect of the latter is weaker. Thus, for the higher contents
      of Rg1, P ginseng is a stimulant, whereas the Rb1 contents of P quinquefolium are
      mainly calming to the CNS. Re, Rg1, panaxan A and B from P ginseng are good for
      diabetes. Re and Rg1 enhance angiogenesis, whereas Rb1, Rg3 and Rh2 inhibit it.
      Rh2, an antitumor agent, can be obtained from Rb1 by steaming. The content of Re
      in P quinquefolium are higher than in P ginseng by 3-4 times. The vasorelax,
      antioxidant, antihyperlipidemic, and angiogenic effects of Re are reported. Thus,
      for the CNS "hot," wound healing and hypoglycemic effects, P ginseng is better
      than P quinquefolium. For anticancer effects, P quinquefolium is better.

PMID- 18718180
TI  - Botanical characteristics, pharmacological effects and medicinal components of
      Korean Panax ginseng C A Meyer.
AB  - Korean Panax ginseng C A Meyer is mainly used to maintain the homeostasis of the
      body, and the pharmacological efficacy of Korean ginseng identified by modern
      science includes improved brain function, pain-relieving effects, preventive
      effects against tumors as well as anti-tumor activity, enhanced immune system
      function, anti-diabetic effects, enhanced liver function, adjusted blood
      pressure, anti-fatigue and anti-stress effects, improved climacteric disorder and
      sexual functions, as well as anti-oxidative and anti-aging effects. Further
      clinical studies of these pharmacological efficacies will continue to be carried
      out. Korean ginseng is found to have such main properties as ginsenoside,
      ployacetylene, acid polysaccharide, anti-oxidative aromatic compound, and insulin
      like acid peptides. The number of ginsenoside types contained in Korean ginseng
      (38 ginsenosides) is substantially more than that of ginsenoside types contained
      in American ginseng (19 ginsenosides). Furthermore, Korean ginseng has been
      identified to contain more main non-saponin compounds, phenol compounds, acid
      polysaccharides and polyethylene compounds than American ginseng and Sanchi
      ginseng.

PMID- 18718182
TI  - Panax ginseng natural populations: their past, current state and perspectives.
AB  - AIM: The mating system of Panax ginseng, genetics and ontogenetic structure of
      its natural populations of Primorye (Russia) were investigated. METHODS: Genetic
      diversity was assessed using allozyme and the fluorescently based automated
      amplified fragment length polymorphism (AFLP) and simple sequence repeats (SSR)
      markers. RESULTS: Total genetic diversity at species level is low with allozyme
      assay (0.023), and high with AFLP (0.255) and SSR (0.259) methods. It is observed
      within populations according to allozyme (> 99%), AFLP (> 85%), and SSR (> 73%)
      assays. The indices of genetic variability distribution point out the re
      colonization of the Sikhote-Alin by ginseng plants from southern refuges during
      the warming period in the early Holocene. The capability of ginseng plants to
      cross- and self-pollinate was shown and the assumption that Panax ginseng is a
      facultative apomictic plant was confirmed. The reproductive system of ginseng
      possesses high plasticity and stability of the fertilization process that help
      the species to survive in stress conditions. Disturbances caused by external or
      internal factors can be reduced due to the morphogenetic potential of ginseng
      ovule or apomictic embryo development. Analysis of life stages structure of
      ginseng populations demonstrates that all of them are not full-constituents
      because some life stages are absent or occur rarely. CONCLUSION: In all 3
      populations, virgin and young generative individuals are predominant. This means
      that populations studied are viable and the reintroduction of natural ginseng
      population is possible yet.

PMID- 18718181
TI  - Ginsenoside Rg1 activated CaMKIIalpha mediated extracellular signal-regulated
      kinase/mitogen activated protein kinase signaling pathway.
AB  - AIM: We carried out this study to investigate the effect of ginsenoside Rg1 on
      the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/
      MAPK) pathway for understanding its effect on synaptic platicity. METHODS:
      Western blotting and immunostaining were used to examine the phosphorylation of
      ERK1/2, CaMKIIalpha and cAMP response element binding protein (CREB) in PC12
      cells and synaptosomes. The confocal microscopy and fluorescent indicator Fluo-3
      was applied to observe the intracellular calcium ion flux. RESULTS: The
      phosphorylation of ERK1/2 in PC12 cells and synaptosomes incubated with Rg1 was
      increased and reached maximum at 4 min. Rg1 also promoted the transient
      enhancement of upstream calcium ion and activated CaMKIIalpha, which reached
      maximum at 2 min. CREB, the downstream protein, was phosphorylated within 8 min
      in PC12 cells after being incubated with Rg1. Moreover, KN93 partially inhibited
      the activation of ERK1/2, and PD98059 also partially blocked the phosphorylation
      of CREB. CONCLUSIONS: Rg1 activated ERK/MAPK pathway by CaMKIIalpha, and the
      activation of CREB was not only dependent on ERK induced by Rg1, which may
      provide an explanation for the effect of Rg1 on long-term potentiation.

PMID- 18718183
TI  - Biodiversity in cultivated Panax notoginseng populations.
AB  - AIM: Panax notoginseng is a cultivated ginseng species highly valued for its
      various pharmacological activities mostly associated with triterpenoid saponin
      glycosides. It would be of great interest to understand biodiversity in this
      ginseng species after its long history of domestication. METHODS: We collected 92
      random sampled 3-year-old P notoginseng plants from 4 counties of Wenshan
      prefecture in Yunnan province, China and documented their morphological features
      of plant height, stem color, number of leaves/leaflets and dry weight of tap
      root. Their genetic diversity was evaluated by fluorescent amplified fragment
      length polymorphism (fAFLP) analysis. RESULTS: Among the samples collected,
      variable morphological features were observed. For these 4 populations (Zhulijie,
      Shangliuhe, Bazai and Jinbuhuan) analyzed by fAFLP, percentage of polymorphic
      bands among the total number of 582 discrete bands were 74.05%, 45.36%, 38.83%
      and 51.89% respectively. Mean genetic heterozygosity were 0.166, 0.093, 0.094 and
      0.125. On the other hand, Nei genetic distances among populations were all <0.03.
      Further analysis of molecular variance (AMOVA) attributed most (93.5%) genetic
      diversity to within population variation. Principal coordinates analysis (PCA)
      did not group any population distinctively. CONCLUSION: This domesticated ginseng
      species still maintains a fair level of biodiversity and this conclusion is
      consistent with the local practice of non-selective collection of seeds for next
      season planting. There was no genetic drift in populations. Biodiversity of P
      notoginseng can be exploited to improve this important herb through breeding. Two
      possible strategies include inbreeding for pure lines and hybrid breeding with
      genetic divergent parents for hybrid vigor.

PMID- 18718184
TI  - Transport and metabolism of flavonoids from Chinese herbal remedy Xiaochaihu-
      tang across human intestinal Caco-2 cell monolayers.
AB  - AIM: To investigate the limiting factors for oral bioavailability of flavonoids
      derived from the Chinese herbal remedy Xiaochaihu-tang. The investigational
      flavonoids included baicalin, wogonoside, oroxylin-A 7-O-beta
      Dglucopyranosiduronide, liquiritin, liquiritin apioside, isoliquiritin, and
      isoliquiritin apioside, as well as their aglycones baicalein, wogonin, oroxylin
      A, liquiritigenin, and isoliquiritigenin. METHODS: Caco-2 cell monolayers were
      used and the apparent permeability both in apical to basolateral and basolateral
      to apical directions was measured for each investigational compound. Meanwhile,
      chemoinformatics was carried out to provide insight into the mechanism governing
      the permeability. In addition, carrier-mediated transport with or without
      inhibitors, as well as the metabolism by conjugation, was also examined with Caco
      2 cell monolayers for the flavonoids. RESULTS: The investigational flavonoid
      aglycones exhibited favorable membrane permeability, but efficient
      glucuronidation and/or sulfation by the enterocytes may limit their
      bioavailability. For the flavonoid glycosides, their poor membrane permeability
      was found to be caused by high hydrogen-bonding potential. Among the glycosides,
      oroxylin-A 7-O-beta- D-glucopyranosiduronide, isoliquiritin, and isoliquiritin
      apioside were transported under the mediation of the efflux transporters
      multidrug resistance-associated protein and/or P-glycoprotein. CONCLUSION: The
      limiting factors of oral bioavailability for the flavonoids derived from
      Xiaochaihu-tang appeared to include poor membrane permeability, significant
      efflux, and efficient intestinal metabolism by conjugation.

PMID- 18718185
TI  - Efficacy of topical permethrin as repellent against Aedes aegypti's bites.
AB  - Mosquitoes are the most important vectors of infectious diseases and their bites
      are related to several adverse skin reactions. Permethrin impregnated clothes are
      an efficient strategy against arthropods' bites; however, its topical efficacy as
      a repellent has not been well established. We studied the response to permethrin
      lotion 5 percent and N,N-Diethyl-meta-toluamide (DEET) spray 50 percent applied
      to the unprotected forearms of 10 volunteers. Each arm was exposed to 20 female
      mosquitoes of Aedes aegypti. We performed 71 bilateral comparative measurements
      evaluating the timing for the first bites. The average times for the arm without
      the product, with permethrin 5 percent, and with DEET 50 percent were: 7.9
      seconds, 336.2 seconds and 7512.1 seconds. The results showed a significant
      difference between repellency times between either product and unprotected
      controls. In addition, there was a significant difference in time to first bite
      between permethrin and DEET treated arms (p<0.01). Permethrin affords some
      repellent activity against Aedes aegypti bites in this experimental setting.
      However, permethrin's profile of repellency was significantly inferior to that of
      DEET.

PMID- 18718186
TI  - Another threat to the availability of isotretinoin: ocular side effects have
      aviation authorities considering restricting use from (even potential) pilots.
AB  - Current concerns about persistent visual abnormalities after the use of
      isotretinoin may lead the Federal Aviation Administration to further restrict its
      use in pilots or future pilots.

PMID- 18718187
TI  - A quick and simple serum test to differentiate bullous pemphigoid, epidermolysis
      bullosa acquisita, and anti-epiligrin cicatricial pemphigoid.

PMID- 18718188
TI  - Cat-transmitted cutaneous lymphatic sporothricosis.
AB  - Sporotrichosis is the most common of the deep mycoses. In most cases the
      transmission occurs secondary to recent penetrating trauma with plant thorns,
      wood splinters or contaminated organic material. We report a case of a 68-year
      old Brazilian female with a small ulcer on her right forefinger and palpable
      erythematous nodules on her right forearm. These occurred after the bite of a
      domestic cat that had a lesion on its hind-foot. Since the 1980s, the role of
      felines in the transmission of this mycosis to humans has gained attention among
      animal owners, veterinarians, and caretakers. Humans can be contaminated by a cat
      scratch or bite and even by contact with contaminated solutions.

PMID- 18718189
TI  - Neutrophilic dermatosis of the dorsal hands associated with hypopharyngeal
      carcinoma.
AB  - Neutrophilic dermatosis of the dorsal hands (NDDH) is a rare and recently
      described disorder regarded as a subset of neutrophilic dermatosis, similar to
      superficial pyoderma gangrenosum and pustular vasculitis. Many currently consider
      it to be a localized variant of Sweet Syndrome. We describe the case of a 63-year
      old male patient with NDDH associated with hypopharyngeal carcinoma. A biopsy
      demonstrated changes consistent with those seen in Sweet Syndrome, with
      leukocytoclasia but no signs of true vasculitis. Treatment with oral prednisolone
      resulted in complete resolution of the lesions in 1 month, with no recurrences.
      The clinical presentation, the histological features, and the excellent response
      to oral corticosteroid therapy allowed us to classify this case as NDDH. We
      emphasize the rare association of this entity with a solid tumor.

PMID- 18718190
TI  - Merkel cell carcinoma: an unusual indication for isolated limb perfusion.
AB  - Isolated limb perfusion (ILP) is a surgical technique that enables the
      administration of high-dose chemotherapy while minimizing serious systemic side
      effects. The clinical value and indications are well established for skin and
      soft tissue tumors on limbs. For skin tumors, this technique is mainly indicated
      for melanoma with in-transit metastasis. For soft tissue tumors--sarcoma and
      osteosarcoma--it is useful as a palliative technique to reduce the tumoral mass.
      Limb perfusion can also be an option in other tumors, such as advanced stage
      squamous cell carcinoma or Merkel cell carcinoma. We present a case report of a
      68-year-old man with Merkel cell carcinoma on the right tibiotarsical region,
      with in-transit metastasis throughout the whole lower limb. Regional chemotherapy
      involving ILP with melphalan and tumor necrosis factor-alpha (TNFalpha) was
      performed in order to avoid amputation; the primary tumor was not excised. A
      steady regression of the disease was observed, with complete resolution of all
      visible in-transit metastases at the 45th day post-perfusion. However, systemic
      metastasis leading to fatal outcome occurred 4 months later. Although there was
      no change in the patient's prognosis, ILP was able to avoid limb amputation as it
      controlled local-regional disease and produced complete regional remission. The
      addition of TNFalpha to melphalan in ILP appears to produce greater efficacy in
      the treatment of patients with bulky tumors or a large number of in-transit
      metastases.

PMID- 18718191
TI  - Persistent cutaneous hyperpigmentation after tyrosine kinase inhibition with
      imatinib for GIST.
AB  - Imatinib mesylate, a tyrosine kinase inhibitor targeting the Bcr-Abl protein, c
      kit (KIT) and the platelet-derived growth factor receptors (PDGFR), is an
      important part of the therapeutic armamentarium used in chronic myelogenous
      leukemia and gastrointestinal stromal tumors. A multitude of dermatological
      toxicities occur with the clinical use of this drug, ranging from various acute
      rashes to Steven-Johnson syndrome. Hyperpigmentation of the skin is a less
      frequent side effect. This phenomenon may be linked to alterations in the c-kit
      signaling pathway, which plays an important role in melanogenesis. A similar
      cutaneous phenotypic expression is manifested in families carrying congenital
      tyrosine II domain mutations of c-kit. We present a unique case of long-term
      persistent hyperpigmentation that occurred after the treatment with imatinib and
      describe the possible pathogenetic mechanisms involved. Elucidation of the
      mechanisms of action of imatinib in the skin may open future directions for the
      treatment of pigmentary disorders.

PMID- 18718192
TI  - Brooke-Spiegler syndrome: report of a case of multiple cylindromas and
      trichoepitheliomas.
AB  - We report a case of Brooke-Spiegler syndrome, a rare autosomal dominant disorder
      caused by mutations of the cylindromatosis gene (CYLD) tumor suppressor gene
      resulting in multiple cylindromas and trichoepitheliomas. Treatment of these
      patients can involve surgical excision, laser therapy, or topical applications of
      aspirin derivatives.

PMID- 18718194
TI  - A case of perforating necrobiosis lipoidica in an African American female.
AB  - An African American female with type II diabetes of 4 years duration presents
      with a 3-year history of smooth firm, dark brown plaques focally studded with
      comedone-like papules. Clinically and histologically her lesions were consistent
      with the rare entity perforating necrobiosis lipoidica.

PMID- 18718193
TI  - Cutaneous cryptococcosis of the penis.
AB  - Disseminated cryptococcosis is a well-known opportunistic infection in AIDS
      patients. We report an unusual patient who demonstrated an isolated plaque of
      cryptococcosis on the penis. Resolution of this plaque was obtained after
      treatment with fluconazole, but subsequent cutaneous dissemination occurred that
      was responsive to amphotericin B.

PMID- 18718195
TI  - Perforating necrobiosis lipoidica in a girl with type 1 diabetes mellitus: a new
      case reported.
AB  - Necrobiosis lipoidica is an idiopathic dermatological condition that is strongly
      associated with diabetes mellitus. It is more commonly seen in women than men.
      The average age of onset is 30-40 years. Necrobiosis Lipoidica diabeticorum is an
      extremely rare finding in childhood diabetes. We describe the case of a 13-year
      old girl who has had type 1 diabetes mellitus since she was 8 years old. The
      patient presented with 2 well-defined, persistent plaques with a depressed
      central area and elevated purple peripheral ring, one on the right thigh and the
      other over the lateral left leg. Histopathologic evaluation of the patient's
      biopsy confirmed the diagnosis of necrobiosis lipoidica with transfollicular
      elimination. Our patient is the second pediatric case described with perforating
      necrobiosis lipoidica. We review the literature and discuss clinical features,
      several complications, and the most recent treatment options for necrobiosis
      lipoidica in diabetic children.

PMID- 18718196
TI  - Palisaded encapsulated neuroma (PEN): an often misdiagnosed neural tumor.
AB  - We describe a unique case of a young man with concomitant Fragile X syndrome who
      presented with a dome-shaped pearly papule under the nose that had enlarged over
      9 months. Histology demonstrated a smoothly contoured spindle cell neoplasm of
      the dermis with neuroid structures and foci of palisaded growth, consistent with
      a diagnosis of palisaded encapsulated neuroma (PEN). Palisaded encapsulated
      neuroma is a benign neural neoplasm of the skin or mucosa that displays
      histologic features of both a neurofibroma and a schwannoma. However, unlike
      these tumors, PEN lacks the implications for underlying systemic disease or
      malignancy. Palisaded encapsulated neuroma is a commonly underdiagnosed and
      misdiagnosed tumor that, once identified clinically and histologically, can be
      easily excised without recurrence.

PMID- 18718198
TI  - Acute generalized exanthematous pustulosis due to clindamycin.
AB  - Acute generalized exanthematous pustulosis (AGEP) is a rare skin eruption most
      commonly caused by medications. It is characterized by fever and the acute
      eruption of non-follicular pustules overlying erythrodermic skin. Histopathology
      shows subcorneal pustules with a background of dermal edema and spongiosis,
      leukocytoclastic vasculitis, perivascular eosinophils, and focal necrosis of
      keratinocytes. Three cases of clindamycin induced AGEP have been reported in the
      literature. A case of AGEP due to clindamycin is reported in a patient with
      numerous other drug allergies and without history of psoriasis. Presentation and
      treatment of AGEP are reviewed.

PMID- 18718199
TI  - Localized abdominal idiopathic lipodystrophy.
AB  - Localized loss of subcutaneous tissue can occur after panniculitis, injections of
      corticosteroids and other drugs, or associated with infectious, autoimmune or
      neurologic diseases. The "idiopathic lipoatrophies" are a group of poorly
      characterized diseases, with focal disappearance of subcutaneous fat, and usually
      the thighs, abdomen or the ankles are affected. Three subtypes have been
      described based on clinical presentation: lipoatrophia semicircularis, annular
      lipoatrophy of the ankles and centrifugal lipodystrophy. We describe a 52-year
      old female patient who developed a localized atrophy of the abdominal areas over
      a period of 3 months without any inflammatory signs over the evolution of the
      disease. The patient denied any previous local trauma or medication of any type.
      The atrophy stabilized, showing no progression over the last 6 years. The
      histopathological examination was normal except for the absence of subcutaneous
      fat, although the biopsy was taken down to the fascia. There was no clinical or
      serologic evidence of autoimmune diseases and laboratory testing for Borrelia
      burgdorferi infection was negative. Other causes of localized lipoatrophies were
      excluded and the final diagnosis was localized idiopathic lipodystrophy. Our
      patient is the second report on an abdominal lipodystrophy, with no previous
      inflammatory signs, absence of subcutaneous fat and no associated pathogenic
      factor. There is no established treatment for idiopathic lipodystrophy, and the
      lesions do not tend to resolve spontaneously.

PMID- 18718197
TI  - Milker's callus.
AB  - Calluses are a diffuse area of hyperkeratosis occurring as a normal physiological
      response to chronic, excessive pressure or friction on the skin. They can be
      distinctive occupational stigmata when they occur on the hands. Herein we report
      the occurrence of calluses of the thumb in professional milkers as an
      occupational dermatosis.

PMID- 18718200
TI  - Vesiculobullous lesions in lipoid proteinosis: a case report.
AB  - Vesiculobullous disorders in a child can be a diagnostic challenge. Common causes
      of blisters in early childhood include genodermatoses like epidermolysis bullosa
      and infections like herpes simplex. Lipoid proteinosis may rarely present with
      vesiculobullous lesions in childhood. We report a child, who presented in early
      childhood with blistering dermatosis. On long term follow-up, typical features of
      lipoid proteinosis developed. A high index of suspicion is required when one
      deals with blistering dermatosis in a child.

PMID- 18718201
TI  - Cutaneous lesions as the first manifestation of systemic follicular lymphoma in
      an HIV patient.
AB  - Human immunodeficiency virus (HIV) patients have an increased incidence of
      lymphomas, particularly when there is a significant immunosuppression. Most
      commonly, they are non-Hodgkin B cell type with a high or intermediate grade and
      have an extranodal presentation. We report the case of a 38-year-old man with HIV
      infection who presented with a 1-year history of a painless tumor on the back and
      lymphadenopathies. The diagnosis of B cell lymphoma follicle center cell type was
      established by skin biopsy. Staging included a bone marrow biopsy revealing
      infiltration by the lymphoma and a whole-body computed tomographic scan showing
      multiple cervical and axillary lymphadenopathies with necrotic center. Biopsy of
      an axillary lymph node revealed caseating epithelioid granulomas and Ziehl
      Neelson staining was positive for acid-fast bacilli. The patient started therapy
      for tuberculosis and polychemotherapy for lymphoma with complete response. This
      report illustrates a case of simultaneous occurrence of tuberculosis and systemic
      follicular lymphoma presenting in skin in an HIV patient.

PMID- 18718202
TI  - Moses's Bronze Serpent.

PMID- 18718203
TI  - Radiation-induced temporary alopecia after embolization of cerebral aneurysms.
AB  - A 29-year-old woman underwent 2 endovascular procedures for treatment of
      bilateral carotid-ophthalmic artery aneurysms. After each treatment, transient
      alopecia occurred over the occipital area and is presumed to be radiation
      induced.

PMID- 18718204
TI  - Foreign body granuloma formation secondary to silicone injection.
AB  - Injectable silicone has been used extensively over the last 40 years for soft
      tissue augmentation. Although considered biologically inert, this material has
      been implicated in a variety of adverse reactions including granulomas,
      disfiguring nodules, and lymphedema, sometimes with latent periods of decades.
      Often these complications are a result of the use of industrial grade products
      injected by unlicensed or unskilled practitioners. Here we report a case of
      foreign body granuloma in the thigh secondary to silicone injection in the
      buttocks. Initially the patient did not disclose a cosmetic contouring procedure
      administered by a nonprofessional nine months earlier, making diagnosis
      difficult. We remind clinicians to include foreign body granulomas in the
      differential diagnosis of apparent cellulitis and to question patients about the
      use of injectable fillers.

PMID- 18718205
TI  - Bacterial colonization and antibiotic resistance in children with atopic
      dermatitis.

PMID- 18718207
TI  - A simple aid for objective diagnosis of malignant melanoma.

PMID- 18718206
TI  - Multiple pilomatricomas: cutaneous marker for myotonic dystrophy.
AB  - We report an interesting case of multiple pilomatricomas (MPs) in a patient with
      myotonic dystrophy. Pilomatricoma (calcifying epithelioma of Malherbe) is a
      benign tumor of hair matrix derivation. It usually occurs as a solitary, firm,
      asymptomatic nodule on the face, neck, or proximal upper extremity. Most
      pilomatricomas have activating mutations in the ss-catenin gene (encoded by
      CTNNB1), leading to involvement of the WNT signaling pathway. The resulting gene
      product activates transcription leading to tumorigenesis [1]. Since the onset of
      MPs may precede the signs of myotonic dystrophy, they can serve as potential
      early cutaneous markers for this systemic disease.

PMID- 18718208
TI  - [Treating a psychotic syndrome in 2007].
AB  - It is well established that we have to consider 3 patterns of psychotic symptoms:
      positive (hallucinations, delusion...), negative (affective flatness, autism...)
      symptoms and disorganization (ambivalence, incoherence...). In the past, ECT
      (electroconvulsivotherapy) was the first effective treatment in psychiatry.
      Conventionnal neuroleptics have been determinant in the significant evolution of
      care to psychotic patients. ECT use is now better defined in terms of practise
      and indications. Assessment of new antipsychotic medications is mainly focused on
      efficacy on positive symptoms. Atypical antipsychotics brought improvement in
      treating psychotic syndromes: they are better tolerated and more effective on the
      whole spectrum of psychotic syndromes including emotional symptoms than
      conventional neuroleptics. Atypical antipsychotics have raised questions about
      metabolic and cardiac risks. Compliance remains a cause of failure of many
      antipsychotic treatments. Treating a psychotic syndrome requires complementary
      strategies to medications: conditions of assistance and rehabilitation, choice of
      psychotherapy. Research program are currently orientated towards: -
      identification of prepsychotic symptoms and endophenotypes which can be treatment
      targets; - assessment of putative therapeutical means such a brain stimulation.

PMID- 18718209
TI  - [Involvement of central neurotransmission systems in schizophrenia].
AB  - Psychiatric disorders have a high prevalence in all countries and cultures and
      have a high cost in socio-economic terms. The participation of dopaminergic
      neurotransmission in the pathophysiology of schizophrenia is well known. However,
      until recently, the nature of dopaminergic dysfunctions had not been elucidated.
      Several recent lines of evidence show that (i) the phasic dopaminerginergic
      neurotransmission (as opposed to the tonic) is altered in schizophrenia and (ii)
      such dysfunction does not participate in the aetiology of the disease, but is
      rather the consequence of other dysfunctions. Although the role of serotonergic
      neurotransmission in mood disorders is well known, its involvement in
      schizophrenia is not well documented and is supported only by indirect evidence.
      Finally, the role of glutamatergic neurotransmission in the pathophysiology of
      schizophrenia, previously hindered by the lack of selective tools, has been
      supported by recent studies, but needs to be confirmed by further works before
      definite conclusions can be reached.

PMID- 18718210
TI  - Cognitive impairment in schizophrenia: a review of developmental and genetic
      models, and pro-cognitive profile of the optimised D(3) > D(2) antagonist,
      S33138.
AB  - In vivo animal models are indispensable both for clarifying the pathological
      bases of schizophrenia, and for evaluating the potential benefits and
      disadvantages of novel therapy. Procedures that model mnemonic impairment are of
      particular interest since currently-available drugs do little to improve
      cognitive symptoms: this is hardly surprising, in fact, since most of them
      potently antagonise histamine H(1), muscarinic, and/or alpha(1)-adrenergic
      receptors. Further, their blockade of D(2) receptors likewise compromises
      cognitive performance. By contrast, D(3) receptor antagonism improves certain
      cognitive domains, suggesting that preferential antagonism of D(3) vs. D(2)
      receptors may permit enhanced effectiveness against cognitive dysfunction. The
      novel agent, S33138, possesses such an "optimised" profile and shows a unique and
      broad-based pattern of pro-cognitive properties in rodents and primates, in the
      absence of extrapyramidal and metabolic side-effects. The present article surveys
      the preclinical pharmacology of S33138. It also reviews developmental and genetic
      risk factors for schizophrenia and their experimental modeling in rodents, with a
      particular emphasis on sensorimotor gating and cognitive deficits.

PMID- 18718211
TI  - [Who is Called "Schizophrenic"?].
AB  - Someone is called "schizophrenic" when suffering from a disorder described in
      1911, for the first time by a Swiss psychiatrist Eugen Bleuler in a book entitled
      "Dementia Praecox oder Gruppe der Schizophrenien". In this book, Bleuler proposes
      a two-faced approach: one centered on the disease, the other on the person.
      Bleuler's main contribution was to show the importance of the latter in the
      determinism of clinical pictures and illness course, thus opening the way to more
      anthropological approaches to the schizophrenic self. Taking these approaches
      into account, at a time when naturalistic models of the illness are prevailing,
      is far from being of no consequence, as far as the effectiveness of our
      therapeutic actions is at issue.

PMID- 18718212
TI  - Markers of D(2) and D(3) receptor activity in vivo: PET scan and prolactin.
AB  - Positrons Emission Tomography (PET) allows to evaluate the dopaminergic activity
      of antipsychotic, by measuring post synaptic D(2) dopaminergic receptors
      occupancy. A good correlation was brought forward between a rate of occupancy of
      80% of striatal D(2) receptors and the occurrence of extrapyramidal effects.
      These PET studies have also established that at least 60% D(2) receptors
      occupancy was predictive of clinical antipsychotic response. The PET studies in
      healthy volunteers can then be used to help choose doses to be tested during the
      clinical trials of new antipsychotic drugs. The increase in prolactin level is
      one other of the markers of the antagonist dopaminergic activity which concerns
      D(2) receptors of the pituitary gland. The example of S 33138, a potential
      antipsychotic, preferential D(3) versus D(2) receptor antagonist will be given to
      illustrate these data. The results of two PET studies as well as the effects on
      prolactin and extrapyramidal signs will be presented.

PMID- 18718213
TI  - [Pharmacogenetics of antipsychotics in schizophrenia].
AB  - There are no objective criterion of choice between the various antipsychotic
      treatments available in schizophrenia today. The final aim of the pharmacogenetic
      study of the efficacy and the tolerance of these treatments is the individual
      optimization of the drug treatments. Research in progress did not make it
      possible yet to highlight criteria usable in daily clinical practice. The
      assessment of larger cohorts, genetically homogeneous and prospectively evaluated
      should in the future make it possible to better predict the response to the
      treatment in particular in term of tolerance, to highlight new therapeutic
      targets and to better understand the mechanism of action of the current
      treatments.

PMID- 18718214
TI  - [The issue of mortality in schizophrenia].
AB  - First and second generation antipsychotic drugs have led to major therapeutic
      advances in the field of schizophrenia. Since the 50ties, they have enable
      schizophrenic patients to be treated as out-patients, contributing to the birth
      of a modern psychiatry. However, several therapeutic targets have not yet been
      reached. This paper will focus on mortality of schizophrenic patients, mortality
      due to suicide or mortality due to somatic conditions. In the future, therapeutic
      research in the field of psychotropic drugs should focus not only on improving
      efficacy on psychic targets and a better profile of tolerance, but also on
      improvement of mortality of schizophrenic patients treated with antipsychotics,
      which should decrease.

PMID- 18718215
TI  - [Prevention in schizophrenia].
AB  - Functional consequences of schizophrenia are important. According to this,
      prevention has been developed using various approaches. The strategy based on the
      neuro-developmental hypothesis of the illness is not useful at the time.
      Identification of ultra high risk groups is an interesting way to develop
      possibilities of intervention which goal is to reduce the possibility of
      transition to psychosis in those samples. But the lack of specificity of the
      definition of those groups, make this strategy difficult to use in general
      population. Increasing the permeability of the different filters along the
      pathway to mental health care can be more promising in general population. By
      now, prevention strategies have to be improved in the filed of schizophrenia, and
      make the proof of ther interest beyond the research perspectives.

PMID- 18718216
TI  - [Development of antipsychotic drug: new directions].
AB  - The treatment of psychotic disorders has been dramatically changed by the
      discovery, in 1952, of antipsychotic activity of chlorpromazine and the
      definition of criteria for a new therapeutic class. Since then, although major
      improvements were done in terms of neurological tolerance and easiness to handle,
      today's antipsychotics are highly similar to former ones. Those treatments do not
      answer to all expectations of patients or practitioners, in particular regarding
      their metabolic or cardiologic side effects and potency to reduce cognitive
      deficit. Moreover, despite increasing understanding of the pathophysiology of
      schizophrenic disorders, this new knowledge is not or very little used in the
      field of therapeutics, justifying to resume research efforts to improve
      therapeutics in psychotic disorders. The development of a new medication follows
      several steps, based on precise strategies and regulations. The main streams of
      research concern compounds that act on dopaminergic, serotoninergic or
      peptidergic systems.

PMID- 18718217
TI  - Presidential address: International medical graduates in the surgical workforce
      and the Veterans Affairs hospitals: where are we coming from? Where are we going?
AB  - The demand for physicians has fluctuated from shortages to oversupply, with
      reliance on international medical graduates (IMGs) during periods of shortages.
      Twenty-four percent of the total physician workforce and 20% of general surgeons
      are IMGs. To address an estimated shortage of 200,000 physicians by 2020 to 2025,
      a constant and stable supply of IMG physicians, in addition to greater numbers of
      graduating medical students is needed. General surgery, especially in underserved
      areas, will be severely affected, and little has been done so far to address this
      shortage. Over the years, Veteran Affairs hospitals have addressed physician
      shortages in their facilities by relying on IMGs despite mounting difficulties
      with visa sponsorship. A sensible solution is presented to address general
      surgery shortages in the United States while preventing global brain drain.

PMID- 18718218
TI  - Commentary on Itani's presidential address.

PMID- 18718219
TI  - Aggressive hepatic resection for patients with pyogenic liver abscess and APACHE
      II score > or =15.
AB  - BACKGROUND: Most liver abscesses resolve after antimicrobial therapy or
      percutaneous tube drainage (PD). The aim of this study was to evaluate the
      results of hepatic resection (HR) for patients with pyogenic liver abscesses and
      an Acute Physiology and Chronic Health Evaluation II (APACHE II) score > or =15.
      METHODS: We compared the clinical outcomes of 81 patients with APACHE II scores >
      or =15 undergoing PD and/or HR. RESULTS: The failure rate (3 of 65) and double
      treatment rate (32 of 65) in the PD group were significantly higher than in the
      HR group (3 of 35 vs 0 of 35; P = .0002). The mortality rate in the PD group was
      significantly higher than the other 2 groups (14 of 46 vs 2 of 19 and 1 of 16; P
      = .038). The length of hospital stay was significantly shorter and antibiotic use
      less in the HR group than in the PD group (P < .05). CONCLUSIONS: Aggressive HR
      for patients with liver abscesses and APACHE II scores > or =15 produced better
      clinical outcomes.

PMID- 18718220
TI  - Host matters most.

PMID- 18718221
TI  - Outcomes of laparoscopic and open colectomy at academic centers.
AB  - BACKGROUND: Laparoscopic techniques have emerged as a suitable approach for colon
      resection. This study determined and compared the outcomes of patients undergoing
      laparoscopic or open colectomy at United States academic centers. METHODS: Using
      ICD-9-CM codes, we obtained data from the University HealthSystem Consortium
      database for 50,443 patients who underwent open (n = 47,090; 94%) or laparoscopic
      (n = 3,353; 6%) colectomy during a 5-year period (2002 to 2006). Outcomes studied
      included length of stay (LOS), costs, in-hospital morbidity and risk-adjusted
      mortality rates. RESULTS: Mean LOS (open = 11 days and laparoscopic = 7 days) was
      significantly shorter and mean costs (open = $23,000 and laparoscopic = $17,000)
      significantly fewer with the laparoscopic approach. The overall in-hospital
      morbidity rate was significantly lower with laparoscopic colectomy (open = 33%
      and laparoscopic = 24%). The risk-adjusted mortality ratio was comparable between
      groups (open = .9 and laparoscopic = .7). COMMENTS: Despite the major biases
      inherent in this retrospective review of the University Health System Consortium,
      which favors the use of laparoscopic colectomy by United States academic
      surgeons, laparoscopic colectomy offers the potential of significantly shorter
      LOS, fewer costs, lower in-hospital morbidity rates, and comparable risk-adjusted
      mortality rates compared with open colectomy. Laparoscopic colectomy is as safe
      as the open approach.

PMID- 18718223
TI  - A historic perspective on the contributions of surgeons to the understanding of
      acute pancreatitis.
AB  - BACKGROUND: Acute pancreatitis is a disease with a broad spectrum of
      presentation, severity, and treatment. Current management involves a
      multidisplinary team of surgeons, gastroenterologists, and interventional
      radiologists whose varied clinical skills contribute to the evolving diagnostic
      and therapeutic strategies for this disease. However, critical aspects of therapy
      have remained the responsibility of the general surgeon. The purpose of this
      review is to examine the many contributions of surgeons in acute pancreatitis.
      DATA SOURCES: A review of the literature taken from PubMed on seminal articles
      published by surgeons on the subject of acute pancreatitis. CONCLUSIONS: Surgeons
      have made significant contributions to the understanding of the pathophysiology
      and evolution of therapy of acute pancreatitis. The specialty should continue to
      take a leadership role to improve outcomes.

PMID- 18718222
TI  - Molecular targeted therapies for pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer cells express different mutations that increase the
      aggressiveness and confer resistance to conventional chemotherapy and
      radiotherapy. Molecules that selectively bind and inhibit these mutations are
      effective in other solid tumors and are now emerging as a complementary therapy
      in pancreatic cancer. The objective of this review is to describe the effect of
      drugs that inhibit specific mutations present in pancreatic cancer with special
      emphasis on clinical trials. DATA SOURCES: We reviewed the English-language
      literature (MedLine) addressing the role of drugs that target mutations present
      in pancreatic cancer. Both preclinical and clinical studies were included.
      CONCLUSIONS: Preclinical evidence supports the combination of conventional
      approved therapies plus drugs that block epidermal growth factor receptor and
      vascular growth endothelial factor or induce apoptosis. However, most of the
      current clinical evidence is limited to small phase I trials evaluating the
      toxicity and safety of these regimens. The results of additional randomized
      trials that are still undergoing will clarify the role of these drugs in
      pancreatic cancer.

PMID- 18718224
TI  - The open mesh repair of Spigelian hernia.

PMID- 18718225
TI  - The role of radiology in the management of systemic sclerosis.
AB  - Systemic sclerosis is a multisystem connective tissue disorder. Radiology plays
      an integral part in its management, guiding the clinician concerning the onset
      and severity of visceral involvement. After skin involvement, the
      gastrointestinal tract is the most commonly affected system; contrast radiography
      and magnetic resonance imaging (MRI) play a role in diagnosis. Non-specific
      interstitial pneumonia is the most frequent respiratory disease and high
      resolution computed tomography (CT) is the cornerstone of management. In common
      with other rheumatic disorders, the role of cardiac MRI is expanding. Radiography
      remains the main technique in the investigation of skeletal involvement, although
      MRI is useful as a problem-solving tool. Neurological involvement is increasingly
      recognized and the major role of radiology is the exclusion of coexistent
      pathology. We present a thorough review of the role of radiology in the
      management of systemic sclerosis.

PMID- 18718226
TI  - Grey-scale and colour Doppler sonography in the evaluation of children with
      suspected bowel inflammation: correlation with colonoscopy and histological
      findings.
AB  - AIM: To evaluate the correlation of grey-scale and colour Doppler sonography with
      colonoscopy and histology to detect bowel inflammation in children. MATERIAL AND
      METHODS: The records of 72 patients with suspected bowel inflammation were
      reviewed retrospectively. Patients were included in the study if sonography had
      been performed up to 30 days before colonoscopy. Grey-scale and colour Doppler
      sonography were used to evaluate bowel wall thickness and vascularity for the
      detection of distal bowel inflammation. Findings were correlated with colonoscopy
      and histological findings. The sensitivity and specificity of sonographic wall
      thickness to detect inflammation was determined. Spearman's coefficient (rs) was
      used to determine the correlation of Doppler findings with colonoscopy/histology.
      RESULTS: Sonograms of 372 bowel segments were evaluated and results were
      correlated with colonoscopy and histological findings of 352 segments. The
      sensitivity and specificity of sonographic bowel thickness to detect inflammation
      in the terminal ileum and the right colon were high; in the other segments,
      specificity was high but sensitivity was low. The correlation of Doppler
      sonography with colonoscopy and histology to detect inflammation in the terminal
      ileum was strong (rs: 0.84; p<0.001) and in the other segments, weak to moderate;
      when the interval between examinations was shorter than 10 days, the correlation
      was stronger in all segments. Of nine patients with abnormal small bowel
      sonograms but normal colonoscopies, three had Crohn's disease. CONCLUSION:
      Sensitivity and specificity of grey-scale sonography to detect inflammation in
      the terminal ileum and the right colon were high, and the correlation of Doppler
      with colonoscopy and histology was very strong in the same segments.

PMID- 18718227
TI  - Effect of visualization display colour on polyp conspicuity at virtual
      colonoscopy.
AB  - AIM: To investigate the effect of different colour three-dimensional (3D)
      displays on polyp detection at virtual colonoscopy (VC). METHODS: Five VC trained
      observers were shown "brief flashes" (lasting 0.2s) of 125 3D endoluminal image
      snap-shots, repeated for each of six display colours (750 images total). One
      hundred images contained a single polyp (diameter range 5-42 mm) and 25 contained
      no polyp ("normal"). Images were reviewed in random order over five reading
      sessions, readers recording either normality or presence and location of a polyp.
      Multilevel logistic regression was used to examine any influence of colour on
      polyp detection stratified according to polyp size (medium 5-9 mm/large
      >or=10mm). The kappa statistic was used to assess effect of colour on observer
      agreement. RESULTS: Individual reader polyp detection rates ranged between 75
      94%. Compared to the default pink "soft tissue" display, the odds of polyp
      detection were 0.65 (CI 0.41,1.01) for green, 0.82 (0.53,1.30) for blue, 1
      (0.63,1.59) for red, 1.12 (0.7,1.79) for monochrome, and 1.15 for yellow
      (0.72,1.84). Overall, there was no significant difference between the displays
      (p=0.11). Including normal cases, there was no overall difference in correct case
      classification between the six colours (p=0.44). The odds of detecting large
      versus medium polyps was significantly greater for 3/5 observers; odds ratio (OR)
      2.84-10.1, although unaffected by display colour (p=0.3). CONCLUSION: The
      background colour display generally has a minimal effect on polyp detection at
      VC, although green should be avoided.

PMID- 18718228
TI  - CT-guided percutaneous core biopsy of deep face and skull-base lesions.
AB  - AIM: To evaluate the diagnostic accuracy of deep face and skull-base computed
      tomography (CT)-guided core biopsy. MATERIALS AND METHODS: Seventeen patients
      underwent CT-guided percutaneous core biopsies of deep face and skull-base
      lesions. One biopsy was repeated due to a non-diagnostic sample so 18 biopsy
      procedures were evaluated. The 17 lesions were centred within the central skull
      base (n=2), parapharyngeal (n=3), retropharyngeal spaces (n=4), masticator (n=3),
      pterygopalatine fossa (n=1), and deep lobe of parotid (n=4). Subzygomatic (n=7),
      retromaxillary (n=9), suprazygomatic (n=1), and transparotid (n=1) needle
      approaches were used. The diagnostic accuracy was either assessed by a positive
      histological result from the operative specimen or based on treatment response
      and clinical follow-up. RESULTS: No immediate or delayed procedural complications
      were encountered. A histological diagnosis was obtained in 16 of the 18 biopsies
      (89% diagnostic yield). The pathological diagnosis was confirmed by surgical
      excision (5/18 biopsies) and by predicted treatment response or clinical follow
      up (10/18 biopsies). Diagnosis could not be confirmed for three of the 18
      biopsies. The diagnostic accuracy of core biopsy was 13 of 15 (87%) for all
      samples. CONCLUSION: CT-guided percutaneous deep face core biopsy is a safe
      technique with good diagnostic accuracy, allowing diagnosis of benign disease and
      classification of malignant disease.

PMID- 18718230
TI  - Solid pseudopapillary carcinoma of the pancreas: differentiation from benign
      solid pseudopapillary tumour using CT and MRI.
AB  - AIM: To describe the computed tomography (CT) and magnetic resonance imaging
      (MRI) findings that differentiate solid pseudopapillary carcinomas (SPC) from
      benign solid pseudopapillary tumours (SPT) of the pancreas. MATERIALS AND
      METHODS: Preoperative CT or MRI images for 26 patients (eight patients with SPC
      and 18 patients with SPT) were retrospectively reviewed. In addition to the
      general morphological features, the presence of pancreatic duct dilation,
      vascular invasion, and extrapancreatic metastases were comparatively assessed.
      RESULTS: There were no significant differences between pancreatic SPC and benign
      SPT with respect to tumour size, location, capsule thickness, internal
      composition, and pattern of calcification, nor was there any correlation with the
      age and gender of the patients. Pancreatic duct dilation was present in four of
      the eight (50%) SPC patients, and was absent in all benign SPT patients
      (p=0.005). Vascular encasement by the tumour (n=2) and hepatic metastases (n=2)
      were also exclusively demonstrated in SPC patients. Multivariate logistic
      regression analysis showed that pancreatic duct dilation (p=0.001), vessel
      encasement (p=0.027), and metastasis (p=0.027) were the variables that can be
      used to differentiate SPC from benign SPT. CONCLUSION: SPC of the pancreas may
      help to differentiate from benign SPT using the imaging features of aggressive
      behaviour of pancreatic duct dilation and vessel encasement with or without
      extrapancreatic metastases.

PMID- 18718229
TI  - CT and histopathological correlation of congenital cystic pulmonary lesions: a
      common pathogenesis?
AB  - AIM: To determine whether similarities exist in both the imaging and
      histopathological features of congenital cystic lung lesions and whether a more
      appropriate classification would be to adopt the theory of "malinosculation".
      MATERIAL AND METHODS: From the histopathology and computed tomography (CT)
      database, 24 patients (16 male, median age 3 years) with congenital cystic lung
      lesions were identified. CT studies were reviewed for site and characteristics of
      the lesions, parenchymal features, bronchial anatomy, and the presence of a
      feeding systemic vessel. Individual histopathological parameters were also
      correlated with CT data. RESULTS: There were five type 1 congenital cystic
      adenomatoid malformations (CCAMs), six type 2 CCAMs, one type 4 CCAM, one
      bronchial atresia, four pleuropulmonary blastomas (PPBs), and seven
      sequestrations. CCAMs (types 1, 2 and 4), sequestrations and PPBs appeared as
      cystic lesions, with cyst size less than 2 cm in type 2 CCAMs. Sequestrations
      were distinguished radiologically from CCAMs by systemic vessels. Reduced
      pulmonary attenuation was seen in bronchial atresia, type 2 CCAMs and in
      sequestrations. Histopathology showed an overlap in entities with sequestrations
      demonstrating CCAM type 2 histology and segmental atresia noted in both type 2
      CCAMs and sequestrations. PPBs showed histological and imaging overlap with type
      4 CCAMs and were distinguished on histology by the presence of blastematous
      proliferation. CONCLUSIONS: This study demonstrates overlap in the CT appearances
      of congenital cystic lesions. The similarity in CT and histopathology findings
      across the spectrum of developmental lesions supports the hypothesis of a common
      aetiology.

PMID- 18718231
TI  - Sex-related differences in the anteroposterior diameter of the foetal cisterna
      magna.
AB  - AIM: To measure the anteroposterior diameter of the foetal cisterna magna and
      observe whether there are differences according to sex. MATERIALS AND METHODS:
      Three hundred and thirty-seven Chinese women with low-risk pregnancies and a
      singleton foetus between 22 and 38 weeks' gestational age were included in this
      retrospective study. Informed consent of the volunteer subjects and hospital
      authority approval were first obtained. Double-blinded for gender, the
      anteroposterior diameter of the cisterna magna of the foetuses was measured by
      transabdominal sonography. Magnetic resonance imaging (MRI) was used for those
      foetuses with mega cisterna magna. All of the foetuses were healthy by prenatal
      and postnatal examination, including physical and imaging examination. RESULTS:
      The mean anteroposterior diameter of the cisterna magna of all foetuses was
      8.01+/-1.79 mm. The anteroposterior diameter of the cisterna magna had no obvious
      correlation with the gestational age. The mean anteroposterior diameter of the
      cisterna magna of 179 male foetuses was 8.63+/-2.16 mm, and the mean
      anteroposterior diameter of the cisterna magna of 158 female foetuses was 7.87+/
      1.74 mm. The size difference was statistically significant (p<0.001). In the 33
      foetuses with mega cisterna magna, the number of male foetuses was greater than
      female foetuses, and the proportion of the foetuses with mega cisterna magna in
      the male group was significantly higher than the foetuses in the female group
      (p<0.05). CONCLUSION: Male foetuses had slightly larger anteroposterior diameters
      of the cisterna magna than female foetuses. The study would be useful for
      creating normal range values for the cisterna magna of male and female foetuses.

PMID- 18718232
TI  - Comparison of fluoroscopy and radiography in the assessment of colonic transit
      time using radio-opaque markers.

PMID- 18718233
TI  - Evaluation of the upper urinary tract using transureteric ultrasound--a review of
      the technique and typical imaging appearances.
AB  - Ureteric strictures and pelviureteric junction obstruction often present a
      diagnostic conundrum to radiologists, particularly after the first-line
      investigations have failed to provide a definitive answer. Transureteric
      ultrasonography (TUU) is a relatively novel technique performed by the
      radiologist, which uses a miniature endoluminal ultrasound probe to interrogate
      the ureteric anatomy and peri-ureteric soft tissues. In this review, we discuss
      how TUU is performed, and the normal imaging appearances of the ureter and
      surrounding anatomical structures. We also focus on the various pathological
      processes that can be accurately evaluated or diagnosed using TUU including
      lymphadenopathy, calculi, ureteric neoplasms, ureteritis, crossing vessels and
      aneurysms. As TUU is not well established in UK practice as yet, we suggest
      possible indications for its use in the diagnostic work-up of urological patients
      and future applications.

PMID- 18718234
TI  - Upright positional MRI of the lumbar spine.
AB  - Supine magnetic resonance imaging (MRI) is routinely used in the assessment of
      low back pain and radiculopathy. However, imaging findings often correlate poorly
      with clinical findings. This is partly related to the positional dependence of
      spinal stenosis, which reflects dynamic changes in soft-tissue structures
      (ligaments, disc, dural sac, epidural fat, and nerve roots). Upright MRI in the
      flexed, extended, rotated, standing, and bending positions, allows patients to
      reproduce the positions that bring about their symptoms and may uncover MRI
      findings that were not visible with routine supine imaging. Assessment of the
      degree of spinal stability in the degenerate and postoperative lumbar spine is
      also possible. The aim of this review was to present the current literature
      concerning both the normal and symptomatic spine as imaged using upright MRI and
      to illustrate the above findings using clinical examples.

PMID- 18718235
TI  - Upright positional MRI of the lumbar spine.

PMID- 18718236
TI  - Three-dimensional perfused blood volume in hyperacute stroke using 64-section
      MSCT.

PMID- 18718237
TI  - Imaging in renal lymphangiectasia: report of two cases and review of literature.

PMID- 18718238
TI  - Overdosage of intrathecal gadolinium and neurological response.

PMID- 18718239
TI  - Thickening of the peribronchovascular interstitium secondary to acute thoracic
      aortic dissection--ECG-gated imaging should be considered.

PMID- 18718240
TI  - Ultrasound diagnosis of fibroadenoma--is biopsy always necessary?

PMID- 18718253
TI  - Health insurance for all children and youth in the United States: a position
      statement of the Federation of pediatric organizations.

PMID- 18718254
TI  - Autoimmunity and minocycline.

PMID- 18718255
TI  - Families of children with chronic conditions: opportunities to widen the scope of
      pediatric practice.

PMID- 18718256
TI  - Blame vaccine interference, not neonatal immunization, for suboptimal responses
      after neonatal diphtheria, tetanus, and acellular pertussis immunization.

PMID- 18718262
TI  - Recurrence of cardiorespiratory events following repeat DTaP-based combined
      immunization in very low birth weight premature infants.
AB  - We evaluated the tolerance to immunization of 64 very low birth weight preterm
      infants. Thirty-three of the infants experienced a cardiorespiratory event after
      the first vaccination, and 6 of these 33 (18%) had a recurrence after the second
      vaccination, including 2 infants previously discharged to home. A
      cardiorespiratory event associated with the first vaccination was the sole risk
      factor for recurrence identified.

PMID- 18718257
TI  - Newborn screening for cystic fibrosis: a lesson in public health disparities.

PMID- 18718263
TI  - Treatment of Takayasu's arteritis with tumor necrosis factor antagonists.
AB  - Four children with Takayasu's arteritis were treated with tumor necrosis factor
      antagonists because of disease relapse during conventional therapy or as a first
      line agent. Two patients went into remission; in the other 2, the response was
      partial. Anti-tumor necrosis factor agents can have a role in the treatment of
      Takayasu's arteritis; further controlled studies are required.

PMID- 18718264
TI  - The clinical course and genetic defect in the PCFT gene in a 27-year-old woman
      with hereditary folate malabsorption.
AB  - We report 2 sequential homozygous mutations in the recently cloned proton-coupled
      folate transporter (PCFT) gene, resulting in the absence of this protein, in a 27
      year-old woman with hereditary folate malabsorption, normal in all respects
      having completed higher education, who has been treated with parenteral 5
      formyltetrahydrofolate since infancy.

PMID- 18718265
TI  - Neonatal respiratory distress due to bilateral dacrocystoceles.

PMID- 18718266
TI  - Longer treatment with intravenous antibiotics does not decrease rate of renal
      scarring in children with pyelonephritis.

PMID- 18718267
TI  - Delayed introduction of solids does not decrease the incidence of asthma or
      allergic rhinitis.

PMID- 18718268
TI  - Non-pharmacologic therapy may be effective for infants with gastroesophageal
      reflux.

PMID- 18718269
TI  - Antioxidants do not improve early childhood development in children with Down's
      syndrome.

PMID- 18718270
TI  - Poor glycemic control predicts occurrence and progression of microalbuminuria in
      children with type I diabetes.

PMID- 18718271
TI  - 0.9% saline solution for the prevention of hospital-acquired hyponatremia: why is
      there still doubt?

PMID- 18718275
TI  - Mapping the oculomotor system.
AB  - Over the last three decades and together with Bernard Cohen, Volker Henn, Ulrich
      Buttner, and Anja Horn, it has been possible to morphologically identify several
      functional cell groups in the oculomotor system: the medium-sized horizontal
      excitatory and inhibitory burst neurons (EBNs, IBNs) in the paramedian pontine
      reticular formation (PPRF), the more sparsely scattered vertical EBNs in the
      rostral interstitial nucleus of the MLF (RIMLF), and the typically elongated
      omnipause neurons (OPNs) in nucleus raphe interpositus--all essential for the
      generation of saccades. In contrast, the role of the central mesencephalic
      reticular formation (cMRF) in saccades is more complex, as is the morphological
      outlining of its borders. A detailed study of the extraocular motoneurons showed
      that they can be divided into two separate types: those for singly innervated
      (twitch) muscle fibres (SIFs) and those for multiply innervated (non-twitch)
      muscle fibres (MIFs). The two motoneuron types receive different premotor
      afferents, proving that MIF and SIF motoneurons have different functions. The
      cell groups were outlined by different tract tracing methods including rabies
      virus. The localization and histochemical characterization of all these
      functional cell groups in monkey formed the basis for the identification of the
      homologous groups in the human brainstem. Taken together these studies provide a
      neuroanatomical background for understanding clinical eye movement disorders.

PMID- 18718276
TI  - Neuronal signalling expression profiles of motoneurons supplying multiply or
      singly innervated extraocular muscle fibres in monkey.
AB  - Motoneurons of the oculomotor nucleus subserving multiply innervated muscle
      fibres (MIF) receive different afferent inputs from the motoneurons subserving
      singly innervated muscle fibres (SIF). We asked whether MIF and SIF motoneurons
      have different neurotransmitter signalling expression profiles. Adult rhesus
      monkey extraocular muscles were injected with the retrograde tracer cholera
      toxin. Sections were then stained for various neurotransmitter-signalling
      markers. MIF motoneurons showed less glutamate receptor 4 (GluR4) and N-methyl-D
      aspartate receptor 1 (NMDAR1) immunoreactivity, but showed similar amounts of
      glutamic acid decarboxylase (GAD) immunoreactive afferent terminals, compared to
      SIF motoneurons. This difference in excitatory neurotransmitter receptor
      expression may explain selective oculomotor deficits and allow development of
      selective pharmacotherapy in the future.

PMID- 18718277
TI  - Histochemical characterisation of trigeminal neurons that innervate monkey
      extraocular muscles.
AB  - Sensory trigeminal innervation is a consistent feature of extraocular muscles
      across species, in spite of a variable occurrence of muscle spindles. We studied
      the histochemical properties of trigeminal ganglion (TG) cells projecting to the
      extraocular eye muscles to obtain more information about their function. In
      monkey TG neurons were retrogradely filled by tracer injections (cholera toxin
      subunit B; wheat-germ agglutinin) into the belly or myotendinous junction of eye
      muscles; one conjunctival injection served as a control. Retrogradely labelled TG
      neurons were processed for the presence of parvalbumin (PV), substance P (SP), or
      nitric oxide synthase (NOS) by double-immunofluorescence. The results indicate
      that approximately 10% of trigeminal afferents to all parts of the eye muscle are
      PV-positive, whereas around 20% are SP-positive. Twice as many SP-positive TG
      projection neurons were counted after a conjunctival tracer injection, presumably
      relaying nociceptive signals. A surprisingly large population of NOS-positive TG
      cells (30%) was found only after distal tracer injections. Up to now none of
      these TG cell groups could be related to the palisade endings located at the
      myotendinous junction.

PMID- 18718279
TI  - Induced extraocular muscle afferent signals: from pigeons to people.
AB  - While the muscles that move the eyes, the extraocular muscles (EOM), are well
      endowed with proprioceptors, afferent signals from these receptors are usually
      assumed to play little or no role in the control of eye movement. In a series of
      experiments, a suction contact lens was used to impose movements on one eye, thus
      inducing afferent signals. Single unit activity was recorded centrally (to
      examine the interactions between EOM afferent signals and visual or vestibular
      signals), or the movements of the other eye were measured (to investigate their
      effects on the output of the oculomotor system). In a model preparation, the
      decerebrate pigeon, EOM afferent signals modified single unit activity in the
      medial vestibular nucleus, and the third and sixth motor nuclei, during
      sinusoidal vestibular stimulation. When one eye was moved to mimic the vestibulo
      ocular reflex (VOR), movement faster than required for compensation for a given
      head velocity reduced the gain of single unit vestibular responses. In awake,
      alert pigeons the overall output of the VOR, as evidenced by movements of the
      other eye, was modified. In humans, when one eye was impeded, the saccades and
      smooth pursuit executed by the other eye were altered. Taken together, these
      results suggest that EOM afferent signals play a functional role in the shaping
      of eye movement.

PMID- 18718278
TI  - Functional anatomy of the extraocular muscles during vergence.
AB  - Magnetic resonance imaging (MRI) now enables precise visualisation of the
      mechanical state of the living human orbit, enabling inferences about the effects
      of mechanical factors on ocular kinematics. We used 3-dimensional (3D) magnetic
      search coil recordings and MRI to investigate the mechanical state of the orbit
      during vergence in humans. Horizontal convergence of 23 degrees from a remote to
      a near target aligned on one eye was geometrically ideal, and was associated with
      lens thickening and extorsion of the rectus pulley array of the aligned eye with
      superior oblique muscle relaxation and inferior oblique muscle contraction. There
      was no rectus muscle co-contraction. Subjective fusion through a 1 degree
      vertical prism caused a clockwise (CW) torsion in both eyes, as well as variable
      vertical and horizontal vergences that seldom corresponded to prism amount or
      direction. MRI under these conditions did not show consistent torsion of the
      rectus pulley array, but a complex pattern of changes in rectus extraocular
      muscle (EOM) crossections, consistent with co-contraction. Binocular fusion
      during vergence is accomplished by complex, 3D eye rotations seldom achieving
      binocular retinal correspondence. Vergence eye movements are sometimes associated
      with changes in rectus EOM pulling directions, and may sometimes be associated
      with co-contraction. Thus, extraretinal information about eye position would
      appear necessary to interpret binocular correspondence, and to avoid diplopia.

PMID- 18718280
TI  - Monkey primary somatosensory cortex has a proprioceptive representation of eye
      position.
AB  - The visual system is tied to the retina. Because the eyes move in the orbit, and
      the head moves on the body, accurate location of an object in extrapersonal space
      cannot simply result from a visual signal. Instead, the retinal signal must be
      combined with an estimate of where the eyes are in the orbit, and where the head
      is in space, to calculate where that object is relative to the observer. There is
      abundant evidence for eye position signals in various areas of the visual cortex.
      However, the source of that eye position signal is unknown. Estimates of eye
      position can arise from two different sources. One is outflow, an 'efference
      copy' or 'corollary discharge' which might arise from some eye position signal
      used to specify eye position for the eye muscles. The second source is inflow, a
      direct proprioceptive signal from the muscles themselves. Nevertheless, neither a
      proprioceptive representation of eye position nor corollary discharge of a motor
      command for eye position has ever been demonstrated unambiguously in the cerebral
      cortex. We recently discovered the neuronal representation of proprioceptive eye
      position signal in monkey primary somatosensory cortex.

PMID- 18718282
TI  - Dynamic aspects of trochlear nerve palsy.
AB  - Trochlear nerve palsy leads to kinematic aberrations of both the paretic and the
      unaffected eye. During dynamic head roll, the rotation axis of the covered
      paretic or unaffected eye deviates inward, while the rotation axis of the viewing
      paretic or unaffected eye aligns with the line of sight; this convergence of
      rotation axes increases with gaze moving in the direction of the unaffected eye.
      During downward saccades, the trajectories of both eyes curve towards the
      unaffected side; these curvatures increase when the head is rolled to the
      affected side and gaze directed to the unaffected side. Hence, during both
      vestibular evoked and saccadic ocular movements, the unaffected eye shows similar
      kinematic aberrations as the paretic eye. While aberrations of the paretic eye
      can be explained by decreased force of the superior oblique (SO) muscle,
      aberrations of the unaffected eye may be due to increased force parallel to the
      paretic SO in the unaffected eye in accordance with Hering's law. This law, which
      forms the basis of conjugate eye movements, also seems to govern eye
      displacements in unilateral eye muscle palsy.

PMID- 18718281
TI  - Acute superior oblique palsy in the monkey: effects of viewing conditions on
      ocular alignment and modelling of the ocular motor plant.
AB  - We investigated the immediate and long-term changes in static eye alignment with
      acute superior oblique palsy (SOP) in the monkey. When the paretic eye was
      patched immediately after the lesion for 6-9 days, vertical alignment slowly
      improved. When the patch was removed and binocular viewing was allowed, alignment
      slowly worsened. In contrast when a monkey was not patched immediately after the
      lesion vertical alignment did not improve. We also show that a model of the eye
      plant can reproduce the observed acute deficit induced by SOP, but only by
      abandoning Robinson's symmetric simplification of the reciprocal innervation
      relationship within pairs of agonist-antagonist muscles. The model also
      demonstrated that physiologic variability in orbital geometry can have a large
      impact on SOP deficits.

PMID- 18718283
TI  - Ocular motor nerve palsies: implications for diagnosis and mechanisms of repair.
AB  - Measurements of the dynamics of the eyes in ocular motor nerve palsies may aid
      diagnosis, characterize peripheral and central palsies, and reveal adaptive
      properties of the brain. Saccadic and vestibulo-ocular reflex (VOR) functions of
      patients with peripheral and central sixth, and peripheral third and fourth nerve
      palsies were studied by three dimensional magnetic field search coil oculography.
      Combined third and fourth cranial nerve microvascular ischaemic palsy in diabetes
      mellitus produced low ratios of intorsion to adduction amplitudes. Presumed
      isolated third nerve palsy caused higher ratios of adduction to intorsion and
      violations of Listing's law. The VOR in third, fourth, and sixth nerve palsies
      reveals adaptive equilibration of the action of paretic agonist and their non
      paretic antagonist muscles in violation of Hering's law during head motion.
      Saccadic speeds in the field of paretic agonists are repaired in chronic
      peripheral palsies despite limited ductions, but remain reduced in central
      palsies. Limited intorsion with third nerve palsy is attributed to concurrent
      fourth nerve ischaemia in the distribution of the inferolateral trunk of the
      intracavernous carotid artery. Adaptive repair of the VOR after ocular motor
      nerve palsies reduces asymmetric retinal image slip and binocular disparity, and
      repair of saccadic velocity drives both eyes rapidly and simultaneously into the
      paretic field of motion.

PMID- 18718285
TI  - Neural circuits for triggering saccades in the brainstem.
AB  - Here we review the functional anatomy of brainstem circuits important for
      triggering saccades. Whereas the rostral part of the superior colliculus (SC) is
      considered to be involved in visual fixation, the caudal part of the SC plays an
      important role in generation of saccades. We determined the neural connections
      from the rostral and caudal parts of the SC to inhibitory burst neurons (IBNs)
      and omnipause neurons (OPNs) in the nucleus raphe interpositus. To reveal the
      neural mechanisms of triggering saccadic eye movements, we analysed the effects
      of stimulation of the SC on intracellular potentials recorded from IBNs and OPNs
      in anaesthetized cats. Our studies show that IBNs receive monosynaptic excitation
      from the contralateral caudal SC, and disynaptic inhibition from the ipsilateral
      caudal SC, via contralateral IBNs. Further, IBNs receive disynaptic inhibition
      from the rostral part of the SC, on either side, via OPNs. Intracellular
      recording revealed that OPNs receive excitation from the rostral parts of the
      bilateral SCs, and disynaptic inhibition from the caudal SC mainly via IBNs. The
      neural connections determined in this study are consistent with the notion that
      the "fixation zone" is localized in the rostral SC, and suggest that IBNs, which
      receive monosynaptic excitation from the caudal "saccade zone," may inhibit tonic
      activity of OPNs and thereby trigger saccades.

PMID- 18718284
TI  - Extraocular proprioception and new treatments for infantile nystagmus syndrome.
AB  - Our goal is to develop the proprioceptive hypothesis for nystagmus damping; and
      present the resulting therapies for the treatment of infantile nystagmus syndrome
      (INS) and acquired nystagmus. Contact lenses, cutaneous stimulation, and neck
      muscle vibration damped INS. Four-muscle tenotomy and reattachment was
      hypothesized as a treatment for INS in 1979 and successfully demonstrated to
      improve foveation in a canine model of INS and seesaw nystagmus in 1998 and in
      humans with INS (masked-data, NEI Clinical Trial) in 2003. Subsequently, tenotomy
      successfully damped acquired pendular nystagmus and oscillopsia in two MS
      patients and downbeat nystagmus in another. Tenotomy, used in isolation or
      combination with existing nystagmus and strabismus surgeries, damps different
      types of nystagmus in their plane of action. Recent neuroanatomical and
      neurophysiological discoveries support the hypothesis that proprioception is the
      mechanism for INS damping and allow more realistic models of peripheral ocular
      motor pathways.

PMID- 18718286
TI  - Brainstem circuits controlling lid-eye coordination in monkey.
AB  - In primate, the M-group is a cell cluster in the rostral mesencephalon which
      contains premotor neurons for the levator palpebrae (LP) and upward-pulling eye
      muscles. It is therefore thought to play a role in lid-eye coupling during
      vertical saccades. To further elucidate its role, the afferents to the M-group
      and LP motoneurons were studied in monkeys. Anterograde tracer injections were
      placed in one of the three eye-movement-related areas: 1. superior colliculus
      (SC), 2. interstitial nucleus of Cajal (INC), and 3. the omnipause neuron (OPN)
      region. Injections into the medial SC subtending upward saccades led to afferent
      labelling of the ipsilateral M-group and the adjacent rostral interstitial
      nucleus of the medial longitudinal fascicle (RIMLF), whereas only RIMLF was
      labelled after an injection into the lateral SC subtending downward saccades.
      Both RIMLF and M-group received bilateral projections from INC, but only RIMLF
      received glycineric inputs from the OPN region. This connectivity pattern
      supports the hypothesis that the M-group mediates lid-eye coupling during
      vertical upgaze, but is indirectly driven by collaterals of saccadic burst
      neurons in the RIMLF during lid saccades. A selective projection from the OPN
      area to the LP motoneurons, but not to other oculomotor neurons is reported here
      for the first time. The result is supported by the presence of glycinergic
      terminals only over LP motoneurons, and implies that a subset of OPNs may
      directly trigger saccade-related blinks.

PMID- 18718287
TI  - Defining the pupillary component of the perioculomotor preganglionic population
      within a unitary primate Edinger-Westphal nucleus.
AB  - The primate Edinger-Westphal nucleus (EW) contains perioculomotor preganglionic
      (pIII(PG)) motoneurons that control the lens and pupil. Separate subdivisions
      have been described in EW and termed visceral columns, with the lateral visceral
      column (lvc) reportedly receiving pretectal inputs for the pupillary light
      reflex. However, choline acetyl transferase staining reveals a single paired
      column of cells dorsal to the oculomotor nucleus, suggesting the EW is not
      subdivided. We investigated this issue by transneuronal retrograde labelling of
      pIII(PG) neurons in three monkey species. In all three, pIII(PG) neurons were
      contained in a single column. We have also examined which part of the macaque
      pIII(PG) population receives pretectal input. Injections of biocytin into the
      pretectum anterogradely labelled terminals that lay in close association with
      pIII(PG) motoneurons retrogradely labelled by ciliary ganglion injections of WGA
      HRP. These close associations were concentrated in the ventromedial portion of
      the middle third of EW, suggesting this pIII(PG) region mediates pupillary
      control. In other cases, pretectal WGA-HRP injections, in addition to labelling
      terminals in the EW, produced a circular field of labelled neurons, and terminals
      in the periaqueductal grey, dorsolateral to EW. This region may represent the
      previously designated lvc, but it does not contain pIII(PG) motoneurons.

PMID- 18718288
TI  - Frontal eye field signals that may trigger the brainstem saccade generator.
AB  - Saccades are rapid shifts of gaze that normally place the line of sight on a
      desired target with a single smooth movement. A number of disease states have
      been shown to result in saccadic movements that are fragmented, but still end
      near target position after a multi-step sequence of saccades. Among these
      disorders are Parkinson's disease and late-onset Tay-Sachs disease (LOTS). We
      have recently shown that normal human subjects and monkeys also make some two
      step saccadic responses in cognitively difficult, choice response tasks. In
      monkeys we have been able to record neuronal responses as the animals performed a
      visually guided, choice saccade task. We compared the activity of neurons in the
      superior colliculus (SC) and the cortical frontal eye field (FEF) during the
      majority of trials that were accomplished with single-step saccades with those
      completed with two-step saccades. Several differences in discharge pattern
      aligned on the first saccade were uncovered. Neurons in the rostral and caudal SC
      were not modulated at the time of the first saccade, but a class of FEF neurons
      showed a burst of activity before the first saccade. If these neurons are among
      those known to project to the saccade generator in the brainstem, they could
      trigger the onset of a saccade before the remaining machinery in the saccade
      generator had sufficient activity to sustain the saccade. Overall the results
      suggest that a delicate balance of triggering and sustaining inputs are required
      to produce normal single-step saccades. These neural results may also help to
      clarify the pathology present when fragmented saccades occur in various disease
      states.

PMID- 18718289
TI  - The role of omnipause neurons: why glycine?
AB  - The anatomy and neurophysiology of the saccadic eye movement system have been
      well studied, but the roles of certain key neurons in this system are not fully
      appreciated. Important clues about the functional interactions in the saccadic
      system can be gleaned from the histochemistry of different saccadic neurons. The
      most prominent inhibitory neurons in the circuit are the omnidirectional pause
      neurons (OPN), which inhibit the premotor burst neurons that drive the eye. Most
      inhibitory neurons in the brain transmit gamma-aminobutyric acid (GABA), but OPN
      transmit glycine (Gly). It is interesting to ask whether the saccadic system
      would work any differently if OPN were GABA-ergic. Gly and GABA receptors both
      provide a channel for a hyperpolarizing Cl(-) current that inhibits its target
      neuron. Depolarizing currents that excite the neurons come through several
      channels, including the NMDA receptor (NMDAR). The NMDAR is unique among
      receptors in that it has active sites for two different neurotransmitters,
      glutamate (Glu) and Gly. Gly is a co-agonist that acts to amplify the current
      produced by Glu. We have proposed a model of the saccadic brain stem circuitry
      that exploits this dual role of Gly to produce both inhibition of the saccadic
      circuit during fixation, and to increase its responsiveness, or gain, during
      movements. This suggests that OPNs act more as a regulator of the saccadic
      circuit's gain, rather than as a gate for allowing saccades. We propose a new
      hypothesis: the OPNs play a general role as a modulator of arousal in orienting
      subsystems, such as saccades, pursuit, head movements, etc.

PMID- 18718290
TI  - Applying saccade models to account for oscillations.
AB  - Saccadic oscillations are unwanted back-to-back saccades occurring one upon the
      other that produce a high-frequency oscillation of the eyes (usually 15-30 Hz).
      These may occur transiently in normal subjects, for example, around the
      orthogonal axis of a purely horizontal or vertical saccade, during combined
      saccade-vergence gaze shifts or during blinks. Some subjects may produce saccadic
      oscillations at will, usually with convergence. Pathological, involuntary
      saccadic oscillations such as flutter and opsoclonus are prominent in certain
      diseases. Our recent mathematical model of the premotor circuit for generating
      saccades includes brainstem burst neurons in the paramedian pontine reticular
      formation (PPRF), which show the physiological phenomenon of post-inhibitory
      rebound (PIR). This model makes saccadic oscillations because of the positive
      feedback among excitatory and inhibitory burst neurons. Here we review our recent
      findings and hypotheses and show how they may be reproduced using our lumped
      model of the saccadic premotor circuitry by reducing the inhibitory efficacy of
      omnipause neurons.

PMID- 18718291
TI  - Dynamics of saccadic oscillations.
AB  - The brainstem circuitry underlying saccades is symmetrical with respect to the
      midline. The oculomotor behaviour generated by the circuitry depends on a
      combination of signals passed along fibre tracts and less easily identifiable
      connections, such as those across the midline. The midline crossing connections
      are often affected by developmental disorders which give rise to unstable eye
      movements (see J. Jen, this volume). The connections at the levels of the
      colliculus, pause cells, and neural integrator generate different dynamical
      mechanisms for the development of instabilities, which can be identified in eye
      movement recordings using phase space analysis techniques.

PMID- 18718292
TI  - Effects of failure of development of crossing brainstem pathways on ocular motor
      control.
AB  - Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, inherited
      disorder characterized by a congenital absence of conjugate horizontal eye
      movement with progressive scoliosis developing in childhood in patients who are
      otherwise neurologically intact. Detailed structural neuroimaging studies
      demonstrated abducens nerves and the absence of fibrosis in the extraocular
      muscles, and a remarkably dysmorphic hindbrain, with hypoplasia and flattened,
      butterfly-like medulla with deep midline cleft. Diffusion tensor imaging further
      demonstrated a widespread lack of crossing fibres in the brainstem, supported by
      evoked potential studies showing uncrossed descending motor and ascending sensory
      pathways in HGPPS patients. In these patients, we identified homozygous or
      compound heterozygous mutations in a gene we named ROBO3, which shares homology
      with evolutionarily conserved roundabout genes that are important in neural and
      vascular wiring. Removal of Robo3 in mice led to the absence of commissural
      crossing throughout the spinal cord and hindbrain (and death soon after birth).
      Therefore, ROBO3 is required for hindbrain axon midline crossing and
      morphogenesis in both human and mouse. We continue to investigate how ROBO3
      mutations lead to massive miswiring in the hindbrain and disruption of conjugate
      horizontal gaze. Elucidation of the full extent of the anatomical abnormalities
      in HGPPS awaits improved neuroimaging techniques and detailed pathological
      studies.

PMID- 18718293
TI  - Neuronal evidence for individual eye control in the primate cMRF.
AB  - Previous single unit recordings and electrical stimulation have suggested that
      separate regions of the MRF participate in the control of vergence and conjugate
      eye movements. Neurons in the supraoculomotor area (SOA) have been found to
      encode symmetric vergence [Zhang, Y. et al. (1992). J. Neurophysiol., 67: 944
      960] while neurons in the central MRF, the cMRF, located ventral to the SOA and
      lateral to the oculomotor nucleus are associated with conjugate eye movements
      [Waitzman, D.M. et al. (1996). J. Neurophysiol., 75(4): 1546-1572]. However, it
      remains unknown if cMRF neurons are strictly associated with conjugate movements
      since eye movements were recorded with a single eye coil in monkeys viewing
      visual stimuli at a distance of at least 50 cm. In the current study we addressed
      whether neurons in the cMRF might also encode vergence-related information.
      Interestingly, electrical stimulation elicited disconjugate saccades
      (contralateral eye moved more than the ipsilateral eye) from locations previously
      thought to elicit only conjugate saccades. Single unit recordings in this same
      area made in two rhesus monkeys trained to follow visual stimuli moved rapidly in
      depth along the axis of sight of an individual eye demonstrate that cMRF neurons
      do not simply encode conjugate information during disconjugate saccades; in fact
      our findings provide evidence that cMRF neurons are most closely associated with
      the movement of an individual eye. These results support the hypothesis that the
      midbrain shapes the activity of the pre-motor saccadic neurons by encoding
      integrated conjugate and vergence commands.

PMID- 18718294
TI  - Complex spike activity signals the direction and size of dysmetric saccade
      errors.
AB  - The cerebellar oculomotor vermis (OMV) receives inputs from both the superior
      colliculus (SC) via the nucleus reticularis tegmenti pontis as mossy fibres and
      the inferior olive as climbing fibres. Lesion studies show that the OMV is
      necessary for the saccade amplitude adaptation that corrects persistent motor
      errors. In this study, we examined whether the complex spike (CS) activity due to
      climbing fibre inputs could serve as an error signal to drive saccade adaptation.
      When there was an error during behaviourally induced saccade dysmetrias, the
      probability of CS occurrence depended on the direction and size of the error. If
      this CS activity actually drives saccade adaptation, we speculate that adaptation
      should be equally efficient in all directions and that the course of adaptation
      could have two operating modes.

PMID- 18718295
TI  - Role of the MST-DLPN pathway in smooth pursuit adaptation.
AB  - The smooth pursuit system is able to adapt to challenges associated with
      development or injury to maintain pursuit accuracy. The medial superior temporal
      (MST) cortex and dorsolateral pontine nucleus (DLPN) are major components of the
      cortico-ponto-cerebellar pathway that carries signals including eye and visual
      motion that could play a role in smooth pursuit adaptation. To test this
      possibility, we first studied the effects of unilateral DLPN inactivation on
      pursuit adaptation in two juvenile rhesus monkeys. In a second series of
      experiments, we examined the activity of the MSTd neurons during smooth pursuit
      adaptation. Our results indicate that smooth pursuit adaptation could depend, in
      part, on eye/visual motion information provided by the MST-DLPN pathway to
      cerebellum.

PMID- 18718296
TI  - Lesions of the cerebellar nodulus and uvula in monkeys: effect on otolith-ocular
      reflexes.
AB  - We studied two rhesus monkeys before and after surgical ablation of the nodulus
      and uvula (Nod/Uv) of the cerebellum. Three-axis eye movements were recorded with
      the magnetic-field scleral search coil system during a variety of vestibular and
      ocular motor tasks. Here we describe the effects of the Nod/Uv lesions on dynamic
      (head translation) and static (head tilt) otolith-mediated vestibulo-ocular
      reflexes. The main findings were: 1. eye velocity during sinusoidal vertical
      translation (1.5 Hz) was reduced by 59% in the dark and 36% in the light; 2. eye
      velocity during steps of horizontal translation was reduced, but only in the dark
      and more so during the sustained (constant velocity) than the initial
      (acceleration) part of the response, and 3. there was a torsional nystagmus that
      depended on the position of roll head tilt, but static ocular counterroll was
      unchanged. These results suggest new roles for the Nod/Uv in the processing of
      otolith signals. This is likely important not only for facilitating gaze during
      linear head motion, but also for maintaining postural stability and one's
      orientation relative to gravity. The lesions appeared to have a greater effect on
      responses to vertical motion, particularly in the light (in contrast, responses
      to interaural translation in the light were nearly normal), suggesting a
      particular importance of the Nod/Uv in processing signals arising from the
      sacculi.

PMID- 18718297
TI  - Vergence eye movement signals in the cerebellar dorsal vermis.
AB  - We examined simple-spike activity of Purkinje cells (P-cells) that responded
      during a search task which required both vergence- and frontal-pursuit. Of a
      total of 100 responding P-cells, 16% discharged only for frontal-pursuit, 43%
      only for vergence-pursuit, and 41% for both. Thus, the majority of vermal pursuit
      P-cells modulated their activity during vergence-pursuit. These P-cells also
      discharged for vergence eye movements induced by step target-motion in-depth. The
      majority of vergence related P-cells carried convergence signals with both eye
      velocity and position sensitivities, and they discharged before the onset of
      convergence eye movements. Muscimol infusion into the sites where convergence P
      cells were recorded resulted in a reduction of peak convergence eye velocity, of
      initial convergence eye acceleration, and of frontal-pursuit eye velocity. These
      results suggest specific involvement of the dorsal vermis in vergence eye
      movements.

PMID- 18718298
TI  - Oculomotor anatomy and the motor-error problem: the role of the paramedian tract
      nuclei.
AB  - Anatomical evidence indicates that copies of premotor commands to ocular
      motoneurons are sent to the cell groups of the paramedian tract, whose
      projections constitute a major mossy-fibre input to the floccular region of the
      cerebellum. Damage to this relay impairs gaze-holding, so producing retinal slip
      signals that are also relayed to the flocculus, in this case as climbing-fibre
      input. These observations suggest that the relation between efference copy and
      sensory error is important, and might be used by the cerebellum to learn accurate
      movements. By modelling the flocculus as an adaptive filter using a covariance
      learning rule, we show that in simulation the cerebellar cortex can in fact learn
      to decorrelate efference copy from motor command, and thereby compensate for
      changes to the oculomotor plant. This mechanism appears to be very robust with
      respect to plant characteristics and noise, and can cope with error-signal delay
      provided there is a brainstem site of plasticity. Its general significance is
      that it removes the need for motor-error signals, which are typically unavailable
      and in any case not conveyed by climbing fibres. This appears to be an example
      where anatomical findings have helped address a long-standing problem in adaptive
      control.

PMID- 18718299
TI  - Impulsive testing of semicircular canal function.
AB  - After acute vestibular loss in humans or animals, eye-movement responses to rapid
      horizontal ipsilesional head rotations ("head impulses") show that there is
      severe, permanent impairment of the angular vestibulo-ocular reflex. The basis
      for this appears to be an inhibitory saturation of ipsilesional vestibular nerve,
      and perhaps vestibular nucleus afferents, in response to high-acceleration, off
      direction stimulation of the sole functioning member of any pair of semicircular
      canals. For the clinician, impulsive testing is an easy and reliable way to
      identify severe unilateral as well as bilateral impairment of semicircular canal
      function.

PMID- 18718300
TI  - Inter-ocular differences of the horizontal vestibulo-ocular reflex during
      impulsive testing.
AB  - Impulsive testing, which accurately measures the gain of the vestibulo-ocular
      reflex (VOR) is mostly recorded from only one eye. We measured the horizontal VOR
      of both eyes in response to graded velocity head impulses in 14 normal subjects.
      VOR acceleration gains were similar for each eye in both directions at low
      accelerations, but as head acceleration increased, gains of the adducting eye
      exceeded gains of the abducting eye. These inter-ocular VOR gain differences were
      due to longer latencies but higher accelerations of the adducting eye compared to
      the abducting eye. Consequently, directional VOR gain asymmetry occurred at high
      accelerations if the same eye was always analysed--with an average inter-ocular
      difference of 15.3%. If only the abducting eye was analysed, VOR gains were
      symmetrical in both directions. For accurate measurements of the VOR at high
      accelerations, the inter-ocular VOR gain differences require binocular recording.

PMID- 18718301
TI  - Control of ocular torsion in the rotational vestibulo-ocular reflexes.
AB  - Visual stabilization of the retina during rotational head movements requires that
      in far vision the eyes rotate about the same axis as the head but in opposite
      direction with a gain close to unity (optimal strategy). To achieve this goal the
      vestibulo-oculomotor system must be able to independently control all three
      rotational degrees of freedom of the eye. Studies of the human rotational
      vestibulo-ocular reflexes (VOR) have shown that its spatial characteristics are
      best explained by a strategy that lies halfway between the optimal image
      stabilization and perfect compliance with Listing's law. Here we argue that these
      spatial characteristics are fully compatible with an optimal strategy under the
      condition of a restrained gain of the torsional velocity-to-position integration.
      One implication of this finding is that the rotational VORs must override the
      default operation mode of the ocular plant that, according to recent findings,
      mechanically favours movements obeying Listing's law.

PMID- 18718302
TI  - Do humans show velocity-storage in the vertical rVOR?
AB  - To investigate the contribution of the vestibular velocity-storage mechanism
      (VSM) to the vertical rotational vestibulo-ocular reflex (rVOR) we recorded eye
      movements evoked by off-vertical axis rotation (OVAR) using whole-body constant
      velocity pitch rotations about an earth-horizontal, interaural axis in four
      healthy human subjects. Subjects were tumbled forward, and backward, at 60 deg/s
      for over 1 min using a 3D turntable. Slow-phase velocity (SPV) responses were
      similar to the horizontal responses elicited by OVAR along the body longitudinal
      axis, ('barbecue' rotation), with exponentially decaying amplitudes and a
      residual, otolith-driven sinusoidal response with a bias. The time constants of
      the vertical SPV ranged from 6 to 9 s. These values are closer to those that
      reflect the dynamic properties of vestibular afferents than the typical 20 s
      produced by the VSM in the horizontal plane, confirming the relatively smaller
      contribution of the VSM to these vertical responses. Our preliminary results also
      agree with the idea that the VSM velocity response aligns with the direction of
      gravity. The horizontal and torsional eye velocity traces were also sinusoidally
      modulated by the change in gravity, but showed no exponential decay.

PMID- 18718303
TI  - Preserved otolith function in patients with cerebellar atrophy and bilateral
      vestibulopathy.
AB  - Cerebellar degeneration affects vestibular function. For instance, with lesions
      of the cerebellar flocculus, the ability to adaptively modify the VOR gain is
      markedly reduced, and cerebellar patients may even demonstrate severe vestibular
      deficits. We report five patients (m=3, f=2) with cerebellar disease, in whom
      search-coil head impulse testing revealed reduced gains of the angular VOR, while
      sacculus-mediated myogenic potentials were normal. Preserved static ocular
      counterroll in roll-tilt positions and prominent gravity-dependent modulation of
      downbeat nystagmus (DBN) along the pitch plane demonstrated the integrity of
      otolith (OL) function in these patients as well. Probably, at least in some
      cerebellar patients with marked floccular atrophy, the dissociation between
      impaired semicircular canal (SCC) function and preserved OL function may be
      explained by a predilection of the atrophic process for the flocculus and
      brainstem neurons involved in angular VOR gain control, while structures
      mediating OL function remain widely spared by the cerebellar degeneration. The
      exact pathomechanism leading to the vestibular impairment remains unclear: both a
      primary multi-system-type atrophy involving cerebellar and brainstem vestibular
      structures as well as a mechanism of secondary retrograde degeneration of
      floccular brainstem target neurons mediating SCC function seem plausible.

PMID- 18718304
TI  - Three-dimensional kinematics of saccadic eye movements in humans with cerebellar
      degeneration.
AB  - During saccades, the orientation of the eye velocity axis varies depending on the
      instantaneous eye position. The means by which this eye velocity axis tilting
      arises remains contentious. Some have argued that muscle pulleys in the orbit
      implement the tilts, since they cause the pulling directions of the extraocular
      muscles to change in a manner that depends on instantaneous eye position. Others
      have suggested that the tilting is centrally programmed. In the current study,
      three-dimensional eye and head rotation data were acquired, using the magnetic
      search coil technique, to confirm the presence of eye position-dependent eye
      velocity axis tilting during saccades. We studied normal humans and humans with
      inherited or sporadic cerebellar degeneration. While the humans with cerebellar
      degeneration were noted to have abnormalities in the two-dimensional metrics and
      consistency of their saccades, the eye velocity axis tilts were similar to those
      observed in the normal subjects. Our findings suggest that the cerebellum does
      not encode eye velocity axis tilting during saccades, further supporting the
      notion that these phenomena arise due to the effects of muscle pulleys.

PMID- 18718305
TI  - Inferior olive hypertrophy and cerebellar learning are both needed to explain
      ocular oscillations in oculopalatal tremor.
AB  - A new model of cerebellar learning explains how the cerebellum can generate
      arbitrary output waveforms to adjust output timing in the classical delay
      conditioning. This model can also reproduce the low frequency ocular oscillations
      seen in oculopalatal tremor (OPT). A novel circuit in the cerebellum uses both
      interneurons (INs) and Purkinje cells (PC) to control timing. Brain lesions that
      cause OPT give rise to hypertrophy of the inferior olive (IO) and an increase in
      conductance through gap junctions among IO neurons. When our model is changed in
      this way, the heavily coupled IO becomes an oscillator and generates synchronous
      spike trains at 1-2 Hz. These synchronized spikes do not produce the large
      amplitude, aperiodic waveforms of OPT. However, the synchronized IO signal goes
      to the cerebellar cortex (flocculus) directly, on climbing fibres, and
      indirectly, on mossy fibres from the vestibular nuclei. This creates a
      pathological association between the IO pulse trains on mossy and climbing fibres
      in PC. Variable pendular ocular oscillations emerged from the cerebellum model
      after learning this association. Since electrotonic coupling of IO cells depends
      on connexin proteins, drugs that block gap junctions, such as anti-malarial
      agents, might provide a novel therapy for OPT.

PMID- 18718306
TI  - Impulsive head rotation resets oculopalatal tremor: examination of a model.
AB  - We have described a neuromimetic model of the interaction between the inferior
      olive (IO) and the cerebellum that accounts for symptomatic oculopalatal tremor
      (OPT), a disorder characterized by oscillations of the eyes (nystagmus), palate
      and other branchial muscles. OPT develops months after some brainstem strokes, in
      association with hypertrophic degeneration of the inferior olivary nucleus (IO).
      We hypothesized that OPT requires both (1) a pulsatile oscillator created by
      tighter electrotonic coupling between cells in the IO, and (2) a learned response
      from the cerebellar cortex that combines with the IO pulses to generate the quasi
      pendular oscillations. Since the vestibular nuclei project to both IO and
      vestibulocerebellum, one prediction of the model is that rapid head rotations
      could interrupt the oscillator, effectively resetting the timing of the ocular
      nystagmus. The ocular oscillations in OPT vary in amplitude and phase, making it
      difficult to determine by Fourier analysis whether head perturbations phase-shift
      the nystagmus. We applied complex wavelet analysis to data from four patients
      with OPT and checked whether vestibular stimuli induced a change in phase of the
      nystagmus. First we calculated a threshold for the spontaneous rate of change of
      phase of OPT by comparing many segments of nystagmus waveform with their time
      shifted versions, bootstrapping these arrays, and computing 95% prediction
      intervals for each patient. Then we compared the rate of change of phase due to
      each head perturbation with the threshold for that patient. To minimize the
      effects of the head perturbation itself on the wavelet analysis, we measured
      effects in a plane orthogonal to the head rotation, e.g., effects of horizontal
      head rotations on the torsional component of OPT. In all four patients, the rate
      of change of phase shift increased sharply at the time of the head perturbation,
      and in three the change was judged to be statistically significant. Thus, the
      experimental tests supported the prediction of our model for OPT.

PMID- 18718307
TI  - Human ocular following: evidence that responses to large-field stimuli are
      limited by local and global inhibitory influences.
AB  - Large-field visual motion elicits tracking eye movements at ultra-short latency,
      often termed ocular following responses (OFRs). We recorded the initial OFRs of
      three human subjects when vertical sine-wave gratings were subject to horizontal
      motion in the form of successive 1/4-wavelength steps. The gratings could occupy
      the full screen (45 degrees wide, 30 degrees high) or a number of horizontal
      strips, each 1 degrees high and extending the full width of the display. These
      strips were always equally spaced vertically. In a first experiment, the gratings
      always had a contrast of 32%. Increasing the number of strips could reduce the
      response latency by up to 20 ms, so the magnitude of the initial OFRs was
      estimated from the change in eye position over the initial open-loop period
      measured with respect to response onset. A single (centred) strip (covering 3.3%
      of the screen) always elicited robust OFRs, and three strips (10% coverage) were
      sufficient to elicit the maximum OFR. Increasing the number of strips to 15 (50%
      coverage) had little impact, i.e., responses had asymptoted, and further
      increasing the coverage to 100% (full screen image) actually decreased the OFR so
      that it was now less than that elicited with only one strip. In a second
      experiment, the contrast of the gratings could be fixed at one of the four levels
      ranging from 8% to 64%, and the OFR showed essentially the same pattern of
      dependence on screen coverage except that the lower the contrast, the lower the
      level at which the response asymptoted. This indicated that the asymptote was not
      due simply to some upper limit on the magnitude of the eye movement or the
      underlying motion signals. We postulate that this asymptote is the result of
      normalization due to global divisive inhibition, which has often been described
      in visual-motion-selective neurons in the cortex. We further suggest that the
      decrease in the OFR when the image filled the screen was due to the increased
      continuity of the gratings which we postulate would favour the local inhibitory
      surround mechanisms over the central excitatory ones. This study indicates that
      robust OFRs can be elicited by much smaller motion stimuli than is commonly
      supposed and that introducing spatial discontinuities can increase the efficacy
      of the motion stimuli even while decreasing the area stimulated.

PMID- 18718308
TI  - Short-latency disparity vergence eye movements: dependence on the preexisting
      vergence angle.
AB  - We recorded the vergence eye movements that are elicited at ultra-short latencies
      when binocular disparities are applied to large-field patterns (Busettini, C.,
      Miles, F.A. and Krauzlis, R.J. (1996). J. Neurophysiol., 75: 1392-1410) and
      determined their dependence on the preexisting vergence angle (PVA). The search
      coil technique was used to record the movements of both eyes in four healthy
      subjects (two with presbyopia). Using dichoptic viewing, the two eyes saw
      identical images each consisting of a fixation cross at the centre of a random
      dot pattern in a circular aperture. The subject fixated the crosses and then the
      images (crosses, random dots, windows) moved horizontally (1.5 degrees/s) in
      opposite directions so as to bring the eyes to the desired horizontal vergence
      position without changing the accommodation demand. After a further 800-1200 ms
      to permit fusion at this new vergence angle (now, the PVA), a disparity step was
      applied and, 200 ms later, the screen changed to uniform grey, marking the end of
      the trial. The disparity steps could have one of six magnitudes and four
      directions (crossed, uncrossed, right-hyper, left-hyper) while the PVA was varied
      systematically. The horizontal and vertical disparity vergence responses (DVRs)
      of one of the presbyopes consistently showed robust linear dependence on the PVA
      (r(2)>0.96). The horizontal DVRs of the other three subjects showed no
      sensitivity to the PVA and their vertical DVRs showed only very weak dependence.
      The experiment was repeated on one of the non-presbyopes after cycloplegia, but
      the outcome was the same, indicating that the negative findings were not due to
      the influence of the vergence-accommodation response. Our data indicate that the
      DVRs can be scaled by the PVA, but most subjects do not show this effect, perhaps
      because they relied on other distance cues that are uninformative in our
      experimental situation.

PMID- 18718309
TI  - MSTd neurons during ocular following and smooth pursuit perturbation.
AB  - MSTd neurons in the behaving monkey were investigated during step-ramp smooth
      pursuit eye movements (SPEM), short perturbations of the small visual target
      during ongoing pursuit, and large-field visual stimulation inducing ocular
      following responses (OFR). Neurons responded with short latencies to visual
      motion during OFR. In contrast the non-retinal responses during SPEM and
      perturbations followed the eye movements by 100-150 ms and were in the opposite
      direction to the OFR response. Often neurons were not modulated by the
      perturbation. Although, both the OFR and the perturbation response are
      involuntary eye movements due to visual motion, it seems very unlikely that these
      MSTd neurons with non-retinal responses are involved in their direct control.
      Based on these responses, we suggest that our MSTd neurons may code for gaze
      direction in space based on visual estimates of self-motion and extraretinal
      estimates of eye-in-head motion.

PMID- 18718310
TI  - Neural activity in cortical areas MST and FEF in relation to smooth pursuit gain
      control.
AB  - Two cortical areas that crucially contribute to the generation and maintenance of
      smooth pursuit eye movements (SPEM) are the medial superior temporal area (MST)
      and the pursuit area of the frontal eye fields (FEF). They both project to the
      brainstem premotor structures via different parallel pathways. A special property
      of the pursuit system is the increased sensitivity to retinal image motion for
      increasing pursuit velocities (dynamic gain control), which might be attributed
      to the FEF. On the other hand, MST is regarded as the main site for estimating
      the target velocity in space and therefore for maintaining an ongoing SPEM.
      However, neural activities in these areas during visually driven SPEM have not
      been fully understood. We present a simple model of smooth pursuit gain control
      that comprises population activities, as well as single unit sensitivities with
      respect to eye and retinal image motion in MST and FEF. We show that the
      nonlinear computation necessary for dynamic gain control may be accomplished by
      units that exhibit a curvilinear sensitivity to retinal image motion and eye
      velocity.

PMID- 18718311
TI  - Eye position and cross-sensory learning both contribute to prism adaptation of
      auditory space.
AB  - Optical prisms shift visual space, and through adaptation over time, generate a
      compensatory realignment of sensory-motor reference frames. In humans, prism
      induced lateral shifts of visual space produce a corresponding shift in sound
      localization. We recently reported that sound localization shifts towards
      eccentric eye position, approaching approximately 40% of gaze over several
      minutes. Given that eye position affects sound localization directly, prism
      adaptation may well reflect contributions of both eye position and sensory
      adaptation; while the visual world is shifted by the prisms, the eyes must also
      shift simply to gaze ahead. To test this new concept of prism adaptation, 10
      young (18-27 year) adults localized sound targets before and after 4 h of
      adaptation to base-right or base-left prisms that induced an 11.4 degrees shift
      left or right, respectively. In separate sessions subjects were exposed to: (1)
      natural binaural hearing; (2) diotically presented inputs devoid of meaningful
      spatial cues; or (3) attenuated hearing to simulate hearing loss. These
      preliminary results suggest that the prism adaptation of auditory space is
      dependent on two independent influences: (1) the effect of displaced mean eye
      position induced by the prisms, which occurs without cross-sensory experience;
      and (2) true cross-sensory learning in response to an imposed offset between
      auditory and visual space.

PMID- 18718312
TI  - Hysteresis effects of the subjective visual vertical during continuous quasi
      static whole-body roll rotation.
AB  - Healthy human subjects, when roll tilted in darkness, make systematic errors in
      estimating subjective visual vertical (SVV). Typically, roll tilt underestimation
      occurs at angles beyond 60 degrees (A-effect). At smaller tilt angles,
      overestimation may occur (E-effect). At approximately 135 degrees whole-body roll
      tilt, Kaptein and Van Gisbergen (2004, 2005) found an abrupt A/E transition, the
      exact location of which depended on the preceding rotation direction indicating
      hysteresis. Since this was observed using relatively fast roll velocity, it
      remains unclear whether the described hysteresis is dynamic or static. To clarify
      this uncertainty, we continuously rotated nine healthy subjects about the earth
      horizontal naso-occipital axis, while they performed SVV adjustments every 2 s.
      Starting from the upright position, three full quasi-static constant velocity
      rotations (2 degrees/s) were completed in both directions (CW: clockwise; CCW:
      counterclockwise). SVV deviation from earth-verticality was plotted as a function
      of whole-body roll position. A bimodal Gaussian distribution function was fitted
      to SVV differences between CW and CCW rotations. A-effects (peaks at 88 degrees
      and 257 degrees chair position) at identical whole-body positions were larger
      after rotations from upside-down than after rotations from upright (average peak
      difference: 26 degrees). These results demonstrate static hysteresis for SVV
      estimation.

PMID- 18718313
TI  - Perception of self motion during and after passive rotation of the body around an
      earth-vertical axis.
AB  - We investigated the perception of self-rotation using constant-velocity chair
      rotations. Subjects signalled self motion during three independent tasks (1) by
      pushing a button when rotation was first sensed, when velocity reached a peak,
      when velocity began to decrease, and when velocity reached zero, (2) by rotating
      a disc to match the perceived motion of the body, or (3) by changing the static
      position of the dial such that a bigger change in its position correlated with a
      larger perceived velocity. All three tasks gave a consistent quantitative measure
      of perceived angular velocity. We found a delay in the time at which peak
      velocity of self-rotation was perceived (2-5 s) relative to the beginning or to
      the end of chair rotation. In addition the decay of the perception of self
      rotation was preceded by a sensed constant-velocity interval or plateau (9-14 s).
      This delay in the rise of self-motion perception, and the plateau for the maximum
      perceived velocity, contrasts with the rapid rise and the immediate decay of the
      angular vestibuloocular reflex (aVOR). This difference suggests that the sensory
      signal from the semicircular canals undergoes additional neural processing,
      beyond the contribution of the velocity-storage mechanism of the aVOR, to compute
      the percept of self-motion.

PMID- 18718314
TI  - The freezing rotation illusion.
AB  - The "freezing rotation illusion" refers to decrease in perceived speed of a
      continuously rotating central region when a swaying surround co-rotates. We
      observed the following effects for rotations: First, when the centre and its
      surround are turning in the same direction, and their velocities are
      distinguishable, the perceived speed of the centre is lower than its physical
      speed. Second, when the surround and the centre are counter-rotating, the
      perceived speed of the centre is enhanced. Third, even when the surface size of
      the centre matches the surface size of the surround, swaying of the centre is
      unable to induce significant changes in the perceived speed of the surround,
      whereas swaying of the surround still induces changes in the perceived speed of
      the centre.

PMID- 18718316
TI  - Listing's plane and the otolith-mediated gravity vector.
AB  - The orientation of Listing's plane (LP) was examined under one-g and zero-g
      conditions during parabolic flight and during prolonged spaceflight. Ten healthy
      subjects participated in the parabolic flight study. In zero-g, the orientation
      of LP was consistently altered. LP elevation was tilted backwards by
      approximately 10 degrees (p=0.003). The azimuth angles of the left and right eyes
      also diverged in zero-g, with a statistically significant change (p=0.04) in the
      vergence angle between 6.1 degrees and 11.8 degrees. A discernible dissociation
      in torsional eye position was also observed, which proved to be statistically
      significant (p=0.03). The thickness of LP was found to be of the order of 1
      degree, and was not significantly altered by the transitions between one-g and
      zero-g. The results of the spaceflight measurements demonstrate that this LP re
      orientation persists over 6-month periods in microgravity, and that re-adaptation
      after returning to one-g earthbound conditions proceeds over several days to
      weeks. The findings demonstrate that in contrast to repositioning of the head in
      one-g, the elimination of gravity represents a qualitative change for the
      vestibular and oculomotor systems. It appears that given the lack of voluntary
      control of ocular torsion, the tonic otolith inputs are instrumental in the
      stabilization of torsional eye position and consequently of LP. The observed
      torsional divergence also provides support for the so-called otolith asymmetry
      hypothesis.

PMID- 18718315
TI  - Geometrical considerations on canal-otolith interactions during OVAR and Bayesian
      modelling.
AB  - During constant-velocity rotation about a tilted axis (OVAR), the VOR and the
      rotation perception last indefinitely, but show a striking dependency on tilt
      angle. We show that, during OVAR, a variety of motions can account for the head
      motion relative to gravity. Some of these are in conflict with canal signals, but
      correspond to a lower angular velocity; we suggest that the brain performs a
      trade-off in order to select the best motion. We show that this theory explains
      the effect of tilt angle on velocity estimation during OVAR.

PMID- 18718317
TI  - A reinterpretation of the purpose of the translational vestibulo-ocular reflex in
      human subjects.
AB  - In a prior study we reported that the human translational vestibulo-ocular reflex
      (tVOR) in response to vertical (bob) 2 Hz oscillations generated eye rotations of
      only 60% of those required to keep the eyes pointed at a stationary visual
      target, whether located at near (approximately 17 cm) or far (2 m). Best
      responses occurred in ambient illumination and we concluded that relative image
      motion between the target and background was an important determinant of tVOR
      behaviour. To investigate further how visual conditions influenced tVOR, we
      measured responses as subjects binocularly viewed the bridge of their own nose in
      a mirror at approximately 8.5 cm, a visual condition that required similar
      convergence to viewing the near target, but cancellation of tVOR. Median tVOR
      cancellation gain [(near-viewing response-mirror viewing response)/near-viewing
      response] was 0.81 (range 0.55-0.97), which was substantially greater than the
      gain of smooth visual tracking of a large visual display moving at 2 Hz (median
      gain 0.27, range 0.09-0.42). Thus, visual inputs other than smooth tracking must
      contribute to tVOR cancellation. We then compared tVOR response to 2 Hz bob as
      subjects fixed upon a visual target at 17 cm and viewed a large textured
      background at 1.5 m that was either stationary or moving at 2.1 Hz. Vertical eye
      rotations waxed and waned as a function of the difference between platform and
      background oscillations. These findings support our hypothesis that tVOR evolved
      not to stabilize the image of the target on the fovea, but rather to minimize
      retinal image motion between objects lying in different planes, in order to
      optimize motion parallax information. A geometrically based optimization function
      is proposed to account for tVOR responses at different target distances.

PMID- 18718319
TI  - Differential coding of head rotation by lateral-vertical canal convergent central
      vestibular neurons.
AB  - Convergent inputs from the lateral and vertical semicircular canals (LC and VC)
      to 31 central vestibular-only (VO) and vestibular-plus-saccade (VPS) neurons were
      determined by oscillating monkeys about a spatial vertical axis while the head
      was tilted forward and backward up to 90 degrees. Activity of each neuron varied
      as a function of head tilt. Seven neurons had maximal activation when the head
      was tilted approximately 30 degrees forward (spatial phase), indicating
      convergent inputs from the LC, while peak activation of 10 units occurred with
      the head tilted back approximately 50 degrees, indicating VC input. Fourteen
      neurons had spatial phases that deviated more that 15 degrees from the LC and VC
      planes, indicating convergent inputs from LC and VC. Seven of these neurons had a
      spatial phase less than 15 degrees forward and 35 degrees back, indicating canal
      inputs from both sides. Seven other neurons had spatial phases more that 45
      degrees forward and 65 degrees back, indicating inputs from canals located on the
      same side. Thus, there are two groups of central vestibular neurons: one group
      responds maximally when the head is rotated about a spatial vertical axis in an
      upright position, declining as the head is tilted away from this position.
      Another group responds minimally to rotation in an upright head orientation,
      increasing as the head is tilted away from the upright. A majority of the cells
      also had convergent otolith input. The otolith and canal inputs superposed when
      the animals were rotated about roll and pitch axes from an upright position. This
      insured that these neurons would respond over a broad frequency range from very
      low to high frequencies.

PMID- 18718318
TI  - Dynamics of binocular fixation of targets during fore-aft motion.
AB  - When subjects move in the fore-aft direction, version and vergence are generated
      through the linear vestibulo-ocular reflex (lVOR) and pursuit systems to maintain
      binocular fixation. While the dynamics of pursuit and the lVOR have been studied
      for monocular gaze, the frequencies over which these systems operate to maintain
      binocular fixation are not known. The frequency characteristics of pursuit and
      the lVOR and their interaction were determined in two monkeys that were trained
      to fixate targets at vertical, lateral, and oblique positions on a computer
      screen. Animals were oscillated at 0.05 Hz to 4 Hz along their naso-occipital
      axes while fixating the targets (lVOR+pursuit). Animals were also stationary and
      fixated targets on the screen moving horizontally, vertically, or obliquely over
      approximately 3 degrees at various frequencies up to 1 Hz (pursuit). Eye
      movements were recorded with dual scleral search coils, and Fick angles were
      computed for each eye and compared to target positions. When animals pursued
      targets moving on the screen at low frequencies (0.05 Hz-0.5 Hz), the gains were
      close to unity, and the eyes were in-phase with the target. Pursuit gains
      decreased to approximately 0.5 and phases lagged by approximately 35 degrees as
      the frequencies of target oscillation increased above approximately 0.5 Hz. When
      fixating the targets during fore-aft oscillation (lVOR+pursuit), the gain was
      close to 1.0, and phases were within 10 degrees-15 degrees for frequencies up to
      3 Hz. Thus, although pursuit alone does not contribute to visual following at
      higher frequencies, the interaction of binocular pursuit and the lVOR supported
      accurate binocular fixation for frequencies up to 3 Hz.

PMID- 18718320
TI  - Cyclovergence evoked by up-down acceleration along longitudinal axis in humans.
AB  - We present results of a study of torsional eye movements evoked by earth-vertical
      accelerations along the subject's longitudinal axis. The earth-vertical stimulus
      leads to a gravito-inertial acceleration vector that changes magnitude but not
      direction. It can therefore be viewed as a dynamic change of the gravity level.
      Up-down oscillations induced relatively symmetric cyclovergence (0.6-2.2 degrees
      peak-to-peak). Eyes intorted/extorted for higher/lower effective gravity. The
      phase of this modulation was small relative to chair acceleration. We contrast
      this behaviour to the dynamics of cycloversion in response to interaural
      acceleration, which shows a considerably larger phase lag. This strikingly
      different dynamics suggest a different processing of otolith signals during
      interaural and longitudinal stimulation.

PMID- 18718321
TI  - Oblique gaze shifts: head movements reveal new aspects of component coupling.
AB  - When the head is prevented from moving, it has been clearly demonstrated that the
      horizontal and vertical components of oblique saccades are not independently
      produced. The duration of the smaller of the two components is stretched in time
      to match the duration of the larger component. Several hypotheses have been
      proposed and each can account for the observed interaction between horizontal and
      vertical saccade components. When the head is free to move, gaze shifts can be
      accomplished by combining eye and head movements. During repeated gaze shifts of
      the same amplitude, as head contribution increases, saccade amplitude declines
      but saccade duration increases. Thus, the expected relationship between duration
      and amplitude of saccadic eye movements can be reversed. We have used this
      altered relationship to determine whether the duration of the vertical saccade
      component is affected by the amplitude or the duration of the horizontal
      component. We find that the relative amplitudes of horizontal and vertical
      saccades cannot account for the observed temporal stretching: vertical component
      duration increases despite a decrease in the amplitude of the horizontal
      component. These results are likely inconsistent with models that rely on
      calculating the vector or relative component amplitudes to account for component
      stretching.

PMID- 18718322
TI  - Head movement control during head-free gaze shifts.
AB  - Humans mostly use combined eye-head movements to shift gaze to a new target.
      Here, we discuss head motor control during human gaze shifts. We demonstrate that
      vestibular feedback monitors and guides the head movement on-line. Our results
      further suggest that cerebellar signals play a role in this on-line control,
      possibly by contributing to detect vestibular input indicating deviations from
      the intended movement trajectory.

PMID- 18718323
TI  - Postural changes during eye-head movements.
AB  - We investigated postural sway in young subjects during eye-head movements.
      Subjects stood on the force plate wearing a helmet on which a laser spot was
      attached. Visual targets were presented stepwise at 60 degrees to right and left
      or 50 degrees to upward and downward of the straight-ahead position. Subjects
      were asked to look at the targets quickly by directing the laser spot to the
      target. The anterior-posterior component of centre of pressures (COPs) exhibited
      the largest changes and shortest latencies during downward movements. Most of the
      subjects showed COP changes preceding the onset of downward head movements, and
      these changes were associated with EMG activity of biceps femoris and
      gastrocnemius. When subjects were asked to look at the target only by eyes, no
      consistent change was detected in ground reaction forces. These results indicate
      that the eye-head movements elicited the COP changes that preceded the onset of
      head movements.

PMID- 18718324
TI  - Cortical processing in vestibular navigation.
AB  - Visual and vestibular perceptual processes are intimately related. Previous data
      suggest a reciprocal visual-vestibular inhibition with regard to head motion
      (velocity) perception with each sensory modality mediated by distinct cerebral
      cortical loci. The relationship between visual and vestibular perceptual
      processes with regard to displacement perception is unknown. In a path-reversal
      vestibular navigation task, we investigated the effects of early visual
      deprivation on vestibular perception by comparing performance and strategies
      employed (i.e., displacement vs. velocity matching) by a group of congenitally
      blind subjects to that of a sighted control group. In a second experiment in a
      sighted group, we attempted to disrupt firstly displacement encoding and then
      velocity encoding, during a path-reversal vestibular navigation task, by applying
      repetitive transcranial magnetic stimulation (rTMS) to the right posterior
      parietal cortex (PPC), vs. a left motor cortex control. Our data show that for a
      path-reversal vestibular navigation task, when given free choice, sighted and
      blind subjects can utilize both displacement- and velocity-matching strategies,
      and overall, both groups display equivalent performance in performing the path
      reversal task. In sighted subjects, when rTMS was applied during encoding in the
      path-reversal task, displacement but not velocity encoding was disrupted for
      leftward rotations. In summary, our data suggest that early visual deprivation
      does not degrade the perception of vestibular signals of head velocity or of
      derived percepts of angular displacement. The rTMS results in the sighted group
      show that leftward vestibular-derived displacement perception is encoded in the
      right PPC, an area prominent in visuo-spatial perception. Thus, in contrast to
      current theories of vestibular head velocity perception which involve reciprocal
      inhibition between separate and competing visual and vestibular cortical areas,
      we suggest that at least for displacement perception, visual and vestibular
      derived signals are encoded in a common cortical locus.

PMID- 18718325
TI  - Foot rotation contribution to trunk and gaze stability during whole-body mediated
      gaze shifts: a principal component analysis study.
AB  - Large gaze displacements are mediated by combined motion of the eye, head, trunk,
      and foot. We applied principal component analysis (PCA) to examine the degree of
      variability and linearity in the angular velocity pattern of the various segments
      involved that participate in this task. Ten normal subjects stood up and had to
      visually fixate and realign their bodies with LED targets separated 45 degrees
      apart, ranging from +/-45 to 360 degrees. The outbound movement in this paradigm
      is unpredictable whereas the return (inbound) movement occurs under spatially
      predictable conditions. Under such predictable conditions, subjects generate in
      approximately 15% of the trials gaze shifts, with periods of fairly constant high
      gaze velocity (single-step gaze shifts). PCA showed that gaze velocity
      variability did not change if the feet were rotating or not. Foot velocity was
      variable and showed additional PCs suggestive of non-linear motion components.
      Trunk and head-in-space velocity showed intermediate levels of variability but
      its variability decreased during the foot stepping movements. The results suggest
      that the feet, trunk, and head are less tightly controlled by the central nervous
      system than gaze velocity. Movements of the feet seem to aid trunk stability and
      motion rather than gaze control.

PMID- 18718326
TI  - Supraspinal locomotor control in quadrupeds and humans.
AB  - Locomotion in humans and other vertebrates is based on spinal pattern generators,
      which are regulated by supraspinal control. Most of our knowledge about the
      hierarchical network of supraspinal locomotion centres derives from animal
      experiments, mainly in the cat. Here we summarize evidence that the supraspinal
      network of quadrupeds is conserved in humans despite their transition to
      bipedalism. By use of mental imagery of locomotion in fMRI we found (1),
      locomotion modulates sensory systems and is itself modulated by sensory signals.
      During automated locomotion in healthy subjects cortical sensory inhibition
      occurs in vestibular and somatosensory areas; this inhibition is cancelled in the
      congenitally blind; (2), we delineated separate and distinct areas in the
      brainstem and cerebellum which are remarkably similar to the feline locomotor
      network. The activations found here include homologues to the pacemakers for gait
      initiation and speed regulation in the interfastigial cerebellum and bilateral
      midbrain tegmentum (cerebellar and mesencephalic locomotor regions), their
      descending target regions in the pontine reticular formation, and the rhythm
      generators in the cerebellar vermis and paravermal cerebellar cortex. This
      conservation of the basic organization of supraspinal locomotor control during
      vertebrate phylogeny opens new perspectives for both, the diagnosis and treatment
      of common gait disorders. It is conceivable that electrical stimulation of
      locomotor brain stem centres may initiate and improve gait in selected patients
      suffering from Parkinson's disease or progressive supranuclear palsy.

PMID- 18718327
TI  - Private lines of cortical visual information to the nucleus of the optic tract
      and dorsolateral pontine nucleus.
AB  - The subcortical nucleus of the optic tract and dorsal terminal nucleus of the
      accessory optic system (NOT-DTN), along with the dorsolateral pontine nucleus
      (DLPN), has been shown to play a pivotal role in controlling slow eye movements.
      Both nuclei are known to receive cortical input from striate and extrastriate
      cortex. To determine to what degree this cortical input arises from the same
      areas, and potentially from the same individual neurons, in one set of
      experiments we placed different retrograde tracers into the NOT-DTN and the DLPN.
      In the ipsilateral cortical hemisphere the two projections mainly overlapped in
      the middle temporal (MT) area, the middle superior temporal (MST) area, and the
      visual area in the fundus of the STS (FST) and the surrounding cortex. In these
      areas, neurons projecting to the NOT-DTN or the DLPN were closely intermingled.
      Nevertheless, only 3-11% of the labelled neurons in MT and MST were double
      labelled in our various cases. In a second set of experiments, we identified
      neurons in areas MT and MST projecting to the DLPN and/or to the NOT-DTN by
      antidromic electrical stimulation. Again, neurons projecting to either target
      were located in close proximity to each other and in all subregions of MT and MST
      sampled. Only a small percentage of the antidromically identified projection
      neurons (4.4%) sent branches to both the NOT-DTN and the DLPN. On the population
      level, only neurons activated from the NOT-DTN had a clear preference for
      ipsiversive stimulus movement whereas the neurons activated from the DLPN, and
      neurons not antidromically activated from either target, had no common
      directional preference. These results indicate that the cortical input to the NOT
      DTN and DLPN arises from largely separate neuronal subpopulations in the motion
      sensitive areas in the posterior STS. Only a small percentage of the projection
      neurons bifurcate to supply both targets. These findings are discussed in
      relation to the effects of cortical lesions on the optokinetic and smooth pursuit
      system.

PMID- 18718328
TI  - Gravity perception in cerebellar patients.
AB  - Patients with midline cerebellar atrophy typically suffer from impaired postural
      balance. We asked whether this deficit is, in part, caused by a deficient
      perception of body position relative to gravity, and therefore measured the
      subjective visual vertical (SVV) in patients with degeneration predominantly of
      the midline cerebellar structures (n=11) and age-matched healthy human subjects
      (n=9). On a motorized turntable, subjects were placed in different roll positions
      [0, 75 degrees right ear down (RED), 75 degrees left ear down (LED)] and had to
      align a luminous arrow with the perceived earth-vertical. Both SVV deviations and
      intra-individual SD of SVV adjustments were not significantly different between
      patients and age-matched controls. Our findings suggest that the perception of
      verticality in patients with cerebellar ataxia may only deteriorate in a more
      advanced stage of the disease. To which degree the deterioration of perceived
      vertical is caused by a collateral vestibular impairment, awaits further
      clarification.

PMID- 18718329
TI  - Brain mechanisms for switching from automatic to controlled eye movements.
AB  - Human behaviour is mostly composed of habitual actions that require little
      conscious control. Such actions may become invalid if the environment changes, at
      which point we need to switch behaviour by overcoming habitual actions that are
      otherwise triggered automatically. It is unclear how the brain controls this type
      of behavioural switching. Here we show that the presupplementary motor area (pre
      SMA) in the medial frontal cortex has a function in switching from automatic to
      volitionally controlled action. This was demonstrated using colour-matching
      saccade tasks performed by rhesus monkeys. We found that a group of pre-SMA
      neurons was selectively activated when subjects successfully switched from a
      habitual saccade to a controlled alternative saccade. Electrical stimulation in
      the pre-SMA replaced automatic incorrect saccades with slower correct saccades. A
      further test suggested that the pre-SMA enabled switching by first suppressing an
      automatic unwanted saccade and then boosting a controlled desired saccade. Our
      data suggest that the pre-SMA resolves response conflict so that the desired
      action can be selected. Possible neuronal circuits through which the pre-SMA
      might exert its switching functions will be discussed.

PMID- 18718330
TI  - The frontal eye field as a prediction map.
AB  - Predictive processes are widespread in the motor and sensory areas of the primate
      brain. They enable rapid computations despite processing delays and assist in
      resolving noisy, ambiguous input. Here we propose that the frontal eye field, a
      cortical area devoted to sensorimotor aspects of eye movement control, implements
      a prediction map of the postsaccadic visual scene for the purpose of constructing
      a stable percept despite saccadic eye movements.

PMID- 18718331
TI  - Volition and eye movements.
AB  - Although the conceptual distinction between voluntary and automatic acts seems
      intuitively obvious, its neural basis remains opaque. Assigning volition--or some
      paraphrase such as action selection--to discrete parts of the brain arguably
      tells us nothing about what volition actually is in neural terms. Equally,
      exploring the relative sensitivity of discrete brain areas to manipulations of
      action choice, including its asymptote--free choice--would only be informative if
      voluntary processes could thereby be reliably isolated. Unfortunately, such
      manipulations are subject to ineliminable confounds, such as the complexity of
      the underlying condition-action associations. Here we propose an adaptation of a
      classic oculomotor task--saccadic choice with asynchronous targets--where the
      processes engaged in free choice manifest as interference in the performance of
      an automatic task, thereby circumventing the difficulties in parameterising
      volition. We suggest that this task may be useful in probing deficits in
      voluntary action in pathological states.

PMID- 18718332
TI  - Negative motivational control of saccadic eye movement by the lateral habenula.
AB  - Reward is crucial for survival of animals and influences animal behaviours. For
      example, an approaching behaviour to reward is more frequently and quickly
      elicited when a big reward is expected than when a small reward is expected.
      Midbrain dopamine neurons are thought to be crucial for such reward-based control
      of motor behaviour. Indeed, dopamine neurons are excited by cues predicting
      reward and inhibited by cues predicting no-reward. These excitatory and
      inhibitory signals would then be used for enhancing and depressing sensorimotor
      processing, respectively, in the brain areas targeted by dopamine neurons (e.g.,
      striatum). However, it was unknown which parts of the brain provide dopamine
      neurons with reward-related signals necessary for their responses. We recently
      showed evidence that the lateral habenula transmits reward-related signals to
      dopamine neurons, especially to inhibit dopamine neurons. This recent study
      suggested that the lateral habenula suppresses less rewarding saccadic eye
      movements by inhibiting dopamine neurons. In the present review, we first
      summarize anatomical and functional aspects of the lateral habenula. We will then
      describe our own study. Finally, we will discuss how the lateral habenula, as
      well as dopamine neurons, contributes to the reward-based control of saccadic eye
      movements.

PMID- 18718333
TI  - Eye movements as a probe of attention.
AB  - Most studies of visual attention have used indirect manual reaction time measures
      to make inferences about where processing priority is allocated in the scene. Eye
      tracking offers an important opportunity to probe more directly where attention
      is deployed, in both health and disease. Here we provide a selective overview of
      oculomotor investigations which have demonstrated how attention can be captured
      "bottom-up" by conspicuous elements in the scene as well as how it can be
      allocated "top-down" on the basis of task goals and reward outcomes. We consider
      the concept of salience maps within the brain that might be responsible for
      computing attentional priorities and saccade targets in the visual scene,
      discussing the evidence for their existence. Finally, we consider how one
      supposedly crucial role of attention--that of binding features which belong to an
      object--might operate so that object representations are veridically maintained
      and remapped across eye movements.

PMID- 18718334
TI  - Using transcranial magnetic stimulation to probe decision-making and memory.
AB  - Decision-making and memory are fundamental processes for successful human
      behaviour. For eye movements, the frontal eye fields (FEF), the supplementary eye
      fields (SEF), the dorsolateral prefrontal cortex (DLPFC), the ventrolateral
      frontal cortex and the anterior cingulum are important for these cognitive
      processes. The online approach of transcranial magnetic stimulation (TMS), i.e.,
      the application of magnetic pulses during planning and performance of saccades,
      allows interfering specifically with information processing of the stimulated
      region at a very specific time interval (chronometry of cortical processing). The
      paper presents studies, which showed the different roles of the FEF and DLPFC in
      antisaccade control. The critical time interval of DLPFC control seems to be
      before target onset since TMS significantly increased the percentage of
      antisaccade errors at that time interval. The FEF seems to be important for the
      triggering of correct antisaccades. Bilateral stimulation of the DLPFC could
      demonstrate parallel information-processing transfer in spatial working memory
      during memory-guided saccades.

PMID- 18718335
TI  - Supplementary eye field contributions to the execution of saccades to remembered
      target locations.
AB  - Multiple lines of evidence indicate that an anatomically discrete region within
      the dorsal medial frontal cortex--the supplementary eye field (SEF)--is involved
      in oculomotor control. To delineate this role further, repetitive transcranial
      magnetic stimulation (rTMS; 10 Hz, 500 ms) was administered either immediately
      after the presentation of three-step saccade sequences, or, immediately before
      response execution of memory-guided saccades. In addition, the effects of changes
      to visuospatial and temporal order demands were examined by contrasting
      performance in the presence and the absence of target location information.
      Results revealed that the SEF supports the processing of spatial information
      relevant to saccade amplitude. Independently of the time of stimulation, saccade
      gain was reduced by rTMS applied over the SEF, though only when response
      execution was performed in the absence of target location information. These
      results provide evidence of a causal role for the SEF in oculomotor control in
      the absence of visual feedback.

PMID- 18718336
TI  - Multiple memory-guided saccades: movement memory improves the accuracy of memory
      guided saccades.
AB  - Memory-guided saccades (MGSs) with 3 s memorization delay were recorded in
      healthy subjects using four different paradigms: two "regular" MGS paradigms with
      the peripheral target lit for 0.2 s (MGS2) and for 1.8 s (MGS18); a multiple
      memory-guided saccade (MMGS) paradigm with the target lit for 1.8 s and the
      instruction to perform a visually guided saccade (VGS) towards it before the MGS;
      a trained memory-guided saccades (TMGSs) paradigm where the same target was
      presented so that the subjects should made 10 VGSs before the MGS. The longer
      target presentation interval (MGS18 paradigm) did not improve the accuracy of
      MGS. The execution of the VGSs improved the accuracy of the corrective saccades
      made after the first MGS to drive the eyes closer to the target, and this
      improvement was independent from the number of the VGSs (there was no difference
      between the MMGS and the TMGS paradigms). The VGSs provide a template that
      improves the capability of the corrective saccades to compensate for the residual
      position error at the end of the first saccade.

PMID- 18718337
TI  - Visual vector inversion during memory antisaccades--a TMS study.
AB  - In the memory antisaccade task, subjects are instructed to look at an imaginary
      point precisely at the opposite side of a peripheral visual stimulus presented
      short time previously. To perform this task accurately, the visual vector, i.e.,
      the distance between a central fixation point and the peripheral stimulus, must
      be inverted from one visual hemifield to the other. Recent data in humans and
      monkeys suggest that the posterior parietal cortex (PPC) might be critically
      involved in the process of visual vector inversion. In the present study, we
      investigated the temporal dynamics of visual vector inversion in the human PPC by
      using transcranial magnetic stimulation (TMS). In six healthy subjects, single
      pulse TMS was applied over the right PPC during a memory antisaccade task at four
      different time intervals: 100 ms, 217 ms, 333 ms, or 450 ms after target onset.
      The results indicate that for rightward antisaccades, i.e., when the visual
      target was presented in the left screen-half, TMS had a significant effect on
      saccade gain when applied 100 ms after target onset, but not later. For leftward
      antisaccades, i.e., when the visual target was presented in the right screen
      half, a significant TMS effect on gain was found for the 333 ms and 450 ms
      conditions, but not for the earlier ones. This double dissociation of saccade
      gain suggests that the initial process of vector inversion can be disrupted 100
      ms after onset of the visual stimulus and that TMS interfered with motor saccade
      planning based on an inversed vector signal at 333 ms and 450 ms after stimulus
      onset.

PMID- 18718338
TI  - Predictive signals in the pursuit area of the monkey frontal eye fields.
AB  - In order to pursue a moving target with our eyes, visual motion-signals are
      converted into eye movement commands. Because of delays in processing visual
      information, prediction is necessary to compensate for those response-delays and
      maintain target images on the foveae. Previous studies showed that the majority
      of FEF pursuit neurons receive visual signals related to actual and predicted
      target motion. However, in those studies, discharge related to the memory of
      visual motion could not be separated from that related to prediction. To
      distinguish the two, while fixating a stationary spot, monkeys were required to
      memorize the direction of random dot motion (cue-1). After a delay (delay-1), a
      second cue (cue-2) instructed the monkeys to prepare either pursuit in the
      memorized direction or to maintain fixation. After a second delay (delay-2), the
      monkeys selected the correct response. In virtually all tested neurons that
      showed a visual motion-response to cue-1, the response was not maintained during
      the delay-1. The majority of responsive neurons were modulated during cue-2 and
      delay-2. Changing the delay-2 duration also changed the duration of discharge
      modulation, suggesting that delay-2 modulation was predictive. These results
      suggest that activity related to visual motion-memory was not conveyed by the
      discharge of caudal FEF pursuit neurons.

PMID- 18718339
TI  - Internally generated smooth eye movement: its dynamic characteristics and role in
      randomised and predictable pursuit.
AB  - Although originally examined in the context of prediction, it is now apparent
      that smooth eye movements generated by internal (extra-retinal) mechanisms play a
      role in both predictable and randomised pursuit responses. Internally generated
      responses are characterised by trajectories that begin with an increasing
      acceleration that develops much more slowly than responses generated through
      retinal feedback, but which can, nevertheless, reach high velocities. They can be
      evoked by regularly repeated motion stimuli or by cues that occur at a regular
      time before target motion onset. Although frequently observed as anticipatory
      movements, we now provide evidence that such movements also form the basis of the
      extra-retinal component of a randomised step-ramp response. In such circumstances
      they also build up slowly in the first second or so of the initial response. They
      are normally masked in the presence of visual feedback, but can be revealed by
      prolonged target extinction immediately after response initiation. The key to
      release internally generated responses in both random and predictable conditions
      is expectation of future target motion. The key to their functionality is rapid
      acquisition and storage of velocity and timing information.

PMID- 18718340
TI  - Predictive disjunctive pursuit of virtual images perceived to move in depth.
AB  - Human and nonhuman primates predictively use smooth pursuit and saccades to track
      visual targets that move in a fronto-parallel plane. This behaviour is believed
      to be facilitated by short-term memory of the target motion and/or an efference
      copy of the subject's motor effort. Subjects in our experiments tracked
      dichoptically viewed targets that appeared to move vertically, right or left and
      towards the subject. The virtual image of the target was tracked using
      disjunctive smooth pursuit and saccades. To reveal predictive tracking, targets
      were blanked 100 ms after the onset of motion for intervals of 800 ms. During the
      blanked interval, subjects initiated pursuit and predictively tracked the unseen
      virtual image using memory guided eye movements. Our data are consistent with
      recent electrophysiological studies that describe cells that encode target or eye
      movements in depth when a target is briefly blanked but pursuit is maintained.
      However, predictive pursuit of a virtual target with disjunctive eye movements
      poses a challenge for understanding how a short-term memory store might encode
      the desired eye movement, its coordinate frame, and how it is transformed into
      motor commands.

PMID- 18718341
TI  - Tracking in 3-D space under natural viewing condition.
AB  - To track a small visual target in 3-D space, the two eyes have to move in
      different directions and/or at different velocities. This tracking might be
      accomplished by a disjunctive pursuit system, which uses separate motion
      processing of each individual eye but no disparity signal (hypothesis 1), or by
      the conjugate pursuit and the vergence system (hypothesis 2). To test the
      validity of the two hypotheses we recorded eye movements in five healthy human
      subjects with the scleral search-coil method. A small dim laser stimulus was
      presented on an earth horizontal platform. A position-ramp stimulus was presented
      in eight different directions: rightward or leftward, convergence or divergence,
      or a combination of them. We compared a fusible with an un-fused and a monocular
      viewing condition to assess whether a disparity signal is needed for 3-D
      tracking. Fusion was prevented by a vertical prism. We compared the monocular
      with the prism viewing condition to examine the effect of retinal motion signals
      of either one or both eyes on the tracking performance in the absence of
      disparity signals. Results revealed severe impairment of tracking in depth, while
      tracking in pure horizontal directions remained unaffected during the prism and
      monocular as compared to the binocular viewing condition. These data support
      hypothesis 2.

PMID- 18718342
TI  - Exploring the pulvinar path to visual cortex.
AB  - The primary pathway for visual signals from the retina to cerebral cortex is
      through the lateral geniculate nucleus of the thalamus to primary visual cortex.
      A second visual pathway has been postulated to pass through the thalamic pulvinar
      nucleus and to project to multiple regions of visual cortex. We have explored
      this second visual pathway using a method that allows us to identify the inputs
      and outputs of pulvinar neurons. Specifically, we applied microstimulation in the
      superficial layers of superior colliculus (SC) to test for orthodromic activation
      of pulvinar neurons receiving input from SC. We also microstimulated the cortical
      motion area MT and tested for antidromic activation of pulvinar to identify
      neurons projecting to MT (and to determine the presence of orthodromic input back
      to pulvinar). In this initial report, we concentrate on two observations. First,
      we find that there are clusters of neurons in the pulvinar that receive input
      from SC along with neurons that project to MT or receive input from MT. Second,
      we find that neurons with input from SC have characteristics of the SC
      superficial layers: they respond to visual stimuli but do not discharge before
      saccadic eye movements. Neurons projecting to MT respond similarly to these SC
      input neurons, while those receiving input from MT more frequently show
      directional selectivity as does MT. These findings indicate the visual nature of
      the signals conveyed in this pathway and shed light on the functional role of the
      thalamus in a possible second visual pathway.

PMID- 18718343
TI  - The role of the human pulvinar in visual attention and action: evidence from
      temporal-order judgment, saccade decision, and antisaccade tasks.
AB  - The pulvinar nucleus of the thalamus has been considered as a key structure for
      visual attention functions (Grieve, K.L. et al. (2000). Trends Neurosci., 23: 35
      39; Shipp, S. (2003). Philos. Trans. R. Soc. Lond. B Biol. Sci., 358(1438): 1605
      1624). During the past several years, we have studied the role of the human
      pulvinar in visual attention and oculomotor behaviour by testing a small group of
      patients with unilateral pulvinar lesions. Here we summarize some of these
      findings, and present new evidence for the role of this structure in both eye
      movements and visual attention through two versions of a temporal-order judgment
      task and an antisaccade task. Pulvinar damage induces an ipsilesional bias in
      perceptual temporal-order judgments and in saccadic decision, and also increases
      the latency of antisaccades away from contralesional targets. The demonstration
      that pulvinar damage affects both attention and oculomotor behaviour highlights
      the role of this structure in the integration of visual and oculomotor signals
      and, more generally, its role in flexibly linking visual stimuli with context
      specific motor responses.

PMID- 18718344
TI  - How disturbed visual processing early in life leads to disorders of gaze-holding
      and smooth pursuit.
AB  - When synergistic interactions between visual and oculomotor systems are impaired
      early in life, strabismus, gaze instability, smooth pursuit asymmetry, and loss
      of visual function are likely to occur. These disorders are relatively common,
      permanent, and difficult to treat. We have developed effective animal models for
      infantile strabismus by raising infant monkeys (Macaca mulatta) with restricted
      binocular visual experience. We have found that the specific oculomotor disorders
      that occur with early onset strabismus depend on the type of early visual
      experience. Our approach allows us to examine the neural substrate associated
      with different components of infantile strabismus including latent nystagmus (LN)
      and smooth pursuit asymmetry. For example, we have found LN is most associated
      with loss of binocular visual sensitivity normally present in neurons of
      pretectal nucleus of the optic tract (NOT). In contrast, nasalward bias in smooth
      pursuit of strabismic monkeys could be associated with loss of binocular visual
      and eye movement sensitivity of neurons in medial superior temporal (MST) area.

PMID- 18718345
TI  - Manifest latent nystagmus: a case of sensori-motor switching.
AB  - Latent nystagmus (LN) and manifest latent nystagmus (MLN) are closely associated
      with early visual deprivation and strabismus. In both cases, the eyes oscillate
      horizontally in an involuntary manner and the fast phases always beat towards the
      attending or fixing eye. By simultaneously recording eye movements during the
      dichoptic viewing of dissimilar visual stimuli we present evidence that MLN
      offers a unique opportunity to examine the nature of sensori-motor switching. In
      particular, we show how the nystagmus beat direction is strongly influenced by
      endogenous and exogenous attention. A model describing the possible mechanisms
      underpinning the sensori-motor switching is proposed.

PMID- 18718346
TI  - Eye hyperdeviation in mouse cerebellar mutants is comparable to the gravity
      dependent component of human downbeat nystagmus.
AB  - Humans with cerebellar degeneration commonly exhibit downbeat nystagmus (DBN).
      DBN has gravity-independent and -dependent components, and the latter has been
      proposed to reflect hyperactive tilt maculo-ocular reflexes (tilt-MOR). Mice with
      genetically determined cerebellar ataxia do not exhibit DBN, but they do exhibit
      tonic hyperdeviation of the eyes, which we have proposed to be the DBN
      equivalent. As such, the tilt-MOR might be predicted to be hyperactive in these
      mutant mice. We measured the tilt-MOR in 10 normal C57BL/6 mice and in 6
      tottering, a mutant exhibiting ataxia and ocular motor abnormalities due to
      mutation of the P/Q calcium channel. Awake mice were placed in body orientations
      spanning 360 degrees about the pitch axis. The absolute, equilibrium vertical
      angular deviations of one eye were measured using infrared videooculography. In
      both strains, eye elevation varied quasi-sinusoidally with tilt angle in the
      range of 90 degrees nose-up to 90 degrees nose-down. Beyond this range the eye
      returned to a neutral position. Deviation over +/-30 degrees of tilt was an
      approximately linear function of the projection of the gravity vector into the
      animal's horizontal plane, and can thus be summarized by its slope (sensitivity).
      Sensitivity measured 14.9 degrees/g for C57BL/6 and 20.3 degrees/g for tottering,
      a statistically significant difference. Thus the pitch otolithic reflex of the
      ataxic mutants is hyperactive relative to controls and could explain tonic
      hyperdeviation of the eyes, consistent with the idea that the tonic
      hyperdeviation is analogous to DBN.

PMID- 18718347
TI  - New insights into the upward vestibulo-oculomotor pathways in the human
      brainstem.
AB  - The brainstem vestibulo-oculomotor pathways are not yet fully known. Three
      different excitatory tracts could be involved in the transmission of upward
      vestibular eye movement (VEM) signals and upward eye position (EP) signals to the
      oculomotor nucleus (III): the medial longitudinal fasciculus (MLF), the brachium
      conjunctivum (BC), and the crossing ventral tegmental tract (CVTT). The
      involvement of the MLF pathway originating in the medial vestibular nucleus (MVN)
      in this transmission is experimentally and clinically well established whereas a
      role of the BC appears to be questionable. Furthermore, there is now accumulating
      evidence that the CVTT pathway emerging from the superior vestibular nucleus
      (SVN) also plays an important role in the mediation of excitatory upward EP and
      VEM signals to the III. This duplication of pathways (MVN-MLF and SVN-CVTT) could
      be explained by a supplementary and relatively specific function performed by the
      SVN-CVTT pathway to counteract the gravity pull in the upward eye movement
      system. Various arguments in support of this hypothesis are reviewed.

PMID- 18718348
TI  - Mechanisms of vestibulo-ocular reflex (VOR) cancellation in spinocerebellar
      ataxia type 3 (SCA-3) and episodic ataxia type 2 (EA-2).
AB  - The vestibulo-ocular reflex (VOR) mechanism triggers eye movements as a result of
      head motion in order to keep gaze stationary relative to the world. However, in
      order to shift the direction of the gaze along with head motion, the VOR
      mechanism must be overridden ("cancelled"). Two mechanisms have been proposed to
      explain this cancellation: a reduction of the VOR gain or activation of smooth
      pursuit (SP) eye movements in the opposite direction. We studied VOR cancellation
      using the magnetic search coil in six spinocerebellar ataxia type 3 (SCA-3) and
      four episodic ataxia type 2 (EA-2) patients, conditions that are known to have
      degraded SP but different degrees of VOR impairment. Abnormal VOR was found in
      two of the four EA-2 patients and all of the SCA-3 patients. All subjects
      possessed residual VOR, although when tested using head thrusts it was almost
      negligible in the SCA-3 patients. The EA-2 patients showed essentially no SP and
      the SCA-3 patients had poor SP. However, for all patients, the gain during VOR
      cancellation was comparable to normals. These results provide additional evidence
      that SP cancellation of the VOR cannot be the sole mechanism utilized in
      overriding the VOR in these patients.

PMID- 18718349
TI  - Modelling drug modulation of nystagmus.
AB  - A better understanding of the neural and functional mechanisms underlying drug
      induced changes in pathological nystagmus is likely to improve medical treatment.
      A treatment option for downbeat nystagmus (DBN), a common form of acquired
      fixation nystagmus that often occurs with cerebellar degeneration, is low doses
      of the potassium channel blocker 4-aminopyridine (4-AP). The upward ocular drift
      in DBN has a spontaneous and a vertical gaze-evoked component. Detailed analysis
      of the effect of 4-AP in patients showed that the drug consistently improved the
      gaze-evoked component, but had less effect in reducing the spontaneous drift. We
      show by a combination of computational modelling at the systems level and at the
      neuronal level how this differential effect can be investigated. We have
      previously postulated that DBN is caused by damage to the floccular lobe (FL). 4
      AP, which has been shown to increase the excitability of Purkinje cells (PCs) in
      slice experiments, may thus suppress DBN by partly restoring floccular function.
      We simulated the effect of low concentrations of 4-AP on the cellular level using
      a multicompartment model of a PC, in which we changed ion channel properties to
      simulate damage. The transition from the cellular level to the systems level was
      achieved by constructing a population response. Systems level modelling predicted
      that the effect of 4-AP on the PCs should reduce DBN, but the predicted effect on
      the gaze-dependent component was less than is observed in patients. Our results
      suggest that the beneficial effect of 4-AP on DBN cannot be solely explained by
      its effect at the neuronal level of PCs, and suggests added effects at the level
      of the population of neurons.

PMID- 18718350
TI  - Aminopyridines for the treatment of cerebellar and ocular motor disorders.
AB  - Downbeat nystagmus (DBN) is the most frequent form of acquired persisting
      fixation nystagmus. It is hypothesized to occur when physiological inhibitory
      cerebellar input, namely of the flocculus, to the vestibular nuclei is inhibited.
      The second most frequent form of acquired nystagmus is upbeat nystagmus (UBN).
      UBN is probably caused by an imbalance of vertical vestibulo-ocular reflex tone.
      GABA-ergic substances like baclofen have been used to treat DBN and UBN, but they
      have had only moderate success. Animal experiments have shown that aminopyridines
      [3,4-diaminopyridine (3,4-DAP) and 4-aminopyridine (4-AP)], nonselective blockers
      of the Kv family of voltage-gated potassium channels, increase Purkinje-cell (PC)
      excitability. It was assumed that such enhancement of PC activity could restore
      to normal levels the inhibitory influence of the cerebellar cortex on vertical
      eye movements. On the basis of these assumptions, we evaluated the efficacy and
      underlying mechanisms of aminopyridines in DBN and UBN as well as in another
      cerebellar disorder with an impaired PC function: episodic ataxia type 2 (EA2),
      which is caused by mutations of the PQ-calcium channel. In a placebo-controlled
      trial on 17 patients we demonstrated that 3,4-DAP significantly reduces the
      intensity of DBN. This was confirmed in a recent study with 4-AP, which also
      showed that 4-AP restores gaze-holding ability independently of fixation in DBN.
      The efficacy of 4-AP in UBN was demonstrated in single patients. Finally, in an
      open trial on three patients with EA2 we showed that 4-AP prevents attacks of
      ataxia. This was also found in an animal model (the tottering mouse) of EA2. The
      clinical efficacy of 4-AP in EA2 is being further evaluated in an ongoing
      randomized controlled crossover trial. In conclusion, the use of aminopyridines
      in DBN, UBN, and EA2 is a new treatment principle for vestibular, cerebellar, and
      ocular motor disorders.

PMID- 18718351
TI  - Baclofen, motion sickness susceptibility and the neural basis for velocity
      storage.
AB  - Reduction of the dominant time constant (T(VOR)) of the angular vestibulo-ocular
      reflex (aVOR) by habituation is associated with a decrease in motion sickness
      susceptibility. Baclofen, a GABA(b) agonist, reduces the time constant of the
      velocity storage integrator in the aVOR in a dose-dependent manner. The high
      frequency aVOR gain is unaltered by baclofen. Here we demonstrate that the
      reduction in T(VOR) produced by oral administration of 20 mg of baclofen causes a
      significant reduction in motion sickness susceptibility, tested with roll while
      rotating (RWR). These data show that motion sickness susceptibility can be
      pharmacologically manipulated with a GABA(b) agonist and support our conclusion
      that motion sickness is generated through velocity storage. We also show how
      baclofen acts on velocity storage at the neural level. A vestibular-plus-saccade
      (VPS) neuron was recorded in the rostral medial vestibular nucleus (rMVN) of a
      cynomolgus monkey, an area where we postulate that velocity storage is generated.
      The cell had a time constant during steps of velocity that was close to that of
      the T(VOR). After parenteral administration of baclofen, there was a similar
      decrease in the time constants of the VPS neuron and the T(VOR). This is the
      first demonstration of the concurrence of unit and aVOR time constants before and
      after baclofen. The data support the hypothesis that the velocity storage
      integrator is generated through activity of vestibular-only (VO) and VPS neurons
      in rMVN and suggest that GABA(b) synapses on VO and VPS neurons are likely to be
      involved in the baclofen-induced reduction in motion sickness susceptibility.

PMID- 18718352
TI  - Oculomotor deficits indicate the progression of Huntington's disease.
AB  - The oculomotor deficits associated with Huntington's Disease (HD) are one of the
      earliest signs of disease onset. They include a marked delay in executing
      voluntary saccades and a difficulty inhibiting saccades to task-irrelevant
      stimuli. In addition, HD patients develop a deficit in task-switching, which can
      be demonstrated by the continued adherence to a rule after it has been recently
      changed. These deficits are likely to be the result of a progressive neural
      degeneration of the fronto-striatal system, which is a distinguishing feature of
      HD neuropathology. It is predicted that as the disease progresses the magnitude
      of these specific deficits should increase. We tested a cohort of early HD
      patients and presymptomatic HD gene carriers on a series of oculomotor tasks
      designed to measure saccade initiation, inhibition and rule switch cost. Saccadic
      latencies and error rates in early HD patients were found to be systematically
      higher than controls. Presymptomatic HD subjects showed small increases in
      saccadic latencies and error rates that were in proportion to the predicted age
      of disease onset. These results suggest that saccadometry and a cognitively
      demanding oculomotor task may be useful as an indicator of function in HD.

PMID- 18718353
TI  - Eye movements in visual search indicate impaired saliency processing in
      Parkinson's disease.
AB  - Previous studies have produced contradictory evidence on the nature of the visual
      search impairment in patients with Parkinson's disease (PD). Eye movements were
      measured during multi-target search in nine individuals with mild-to-moderate PD.
      Subjects were asked to click on a response button whenever they judged they were
      fixating a target for the first time. Compared to age-matched healthy volunteers,
      PD patients were impaired at efficient search (detecting "+"s amongst "L"s) but
      not inefficient search ("T"s amongst "L"s). However, these patients had normal
      memory for locations as indexed by their rate of re-clicking on previously
      inspected locations. We suggest that the pattern of gaze for efficient search may
      reflect impaired saliency processing in PD.

PMID- 18718354
TI  - Ocular motor anatomy in a case of interrupted saccades.
AB  - Saccades normally place the eye on target with one smooth movement. In late-onset
      Tay-Sachs (LOTS), intrasaccadic transient decelerations occur that may result
      from (1) premature omnipause neuron (OPN) re-activation due to malfunction of the
      latch circuit that inhibits OPNs for the duration of the saccade or (2) premature
      inhibitory burst neuron (IBN) activation due to fastigial nucleus (FN)
      dysregulation by the dorsal cerebellar vermis. Neuroanatomic analysis of a LOTS
      brain was performed. Purkinje cells were absent and gliosis of the granular cell
      layer was present in the dorsal cerebellar vermis. Deep cerebellar nuclei
      contained large inclusions. IBNs were present with small inclusions. The sample
      did not contain the complete OPN region; however, neurons in the OPN region
      contained massive inclusions. Pathologic findings suggest that premature OPN re
      activation and/or inappropriate firing of IBNs may be responsible for interrupted
      saccades in LOTS. Cerebellar clinical dysfunction, lack of saccadic slowing, and
      significant loss of cerebellar cells suggest that the second cause is more
      likely.

PMID- 18718355
TI  - Mechanism of interrupted saccades in patients with late-onset Tay-Sachs disease.
AB  - In late-onset Tay-Sachs disease (LOTS), saccades are interrupted by one or more
      transient decelerations. Some saccades reaccelerate and continue on before eye
      velocity reaches zero, even in darkness. Intervals between successive
      decelerations are not regularly spaced. Peak decelerations of horizontal and
      vertical components of oblique saccades in LOTS is more synchronous than those in
      control subjects. We hypothesize that these decelerations are caused by
      dysregulation of the fastigial nuclei (FN) of the cerebellum, which fire brain
      stem inhibitory burst neurons (IBNs).

PMID- 18718356
TI  - Conjugacy of horizontal saccades: application of binocular phase planes.
AB  - The goal of this study was to evaluate the ability of binocular phase planes to
      detect disconjugacy of horizontal saccades. We recorded horizontal saccades in 22
      patients with disease affecting the brainstem reticular formation, medial
      longitudinal fasciculus (INO), abducens nerve, neuromuscular junction and
      extraocular muscles, and in 10 age-matched controls. We found that patients with
      disorders of the brainstem, including INO, or the cranial nerves, showed
      significant velocity disconjugacy in the first 10% of the displacement. Patients
      with myasthenia gravis did not show early disconjugacy, but might do so later in
      the course of the saccade. We conclude that binocular phase planes supplement
      conventional measures of saccades, such as peak velocity, and are useful to
      differentiate INO and cranial nerve palsies from myasthenia.

PMID- 18718357
TI  - The neuroanatomical basis of slow saccades in spinocerebellar ataxia type 2
      (Wadia-subtype).
AB  - In a case of spinocerebellar ataxia type 2, Wadia-subtype (SCA2), with slow
      horizontal saccades, we used parvalbumin immunohistochemistry to identify the
      omnipause (OPNs) excitatory (EBNs), and inhibitory burst neurons (IBNs) of the
      saccade generator. Nissl sections was used to measure neuronal diameters, and
      synaptophysin staining to estimate of synaptic density on the cell somata.
      Morphometric and synaptic density measurements of the abducens motoneurons were
      identical in SCA2 and the control. A significant cell loss and reduced synaptic
      density on somata was found only in the EBN area. We conclude that degeneration
      of the EBNs is the most likely cause for the slowing of horizontal saccades.

PMID- 18718358
TI  - Selective, circuit-wide sparing of floccular connections in hereditary
      olivopontine cerebellar atrophy with slow saccades.
AB  - We present a systems-oriented histopathologic analysis of the ocular motor
      control circuits in the cerebellum and brainstem from a patient with a hereditary
      form of olivopontine cerebellar atrophy of the Wadia type, which has a
      characteristic ocular motor presentation of slow saccades but relative
      preservation of smooth pursuit and gaze-holding. This differential pattern of
      clinical involvement is associated with a lobule-specific pattern of cerebellar
      degeneration. We asked whether these patterns of sparing and degeneration were
      consistent throughout the associated deep cerebellar and brainstem structures.
      Specimens were fixed in formalin, embedded in paraffin, and stained for various
      markers. We found that elements of the floccular and nodular pathways,
      controlling smooth pursuit and vestibular reflexes, were relatively spared,
      particularly those structures that are interconnected with the medial regions.
      Conversely, the elements of the dorsal vermis pathway controlling saccade
      adaptation were relatively involved. This subregional specificity of degeneration
      further defines possible areas of investigation for elucidating pathophysiology,
      testing biomarkers of disease, and developing areas for therapeutic intervention.

PMID- 18718359
TI  - A quick look at slow saccades after cardiac surgery: where is the lesion?
AB  - Saccadic palsy is a reported complication of cardiac surgery. One case that came
      to autopsy showed midline pontine gliosis; however, in most cases, no lesions are
      evident on neuroimaging. Since the saccadic palsy may range from single large
      slow saccades to a "staircase" of very small saccades that are normal in speed,
      it seems plausible that more than one mechanism is possible. Here we postulate
      that, in those patients who make a staircase of small saccades, loss of
      cerebellar Purkinje cells could cause fastigial nucleus neurons to fire
      prematurely, thereby decelerating saccades via inhibitory burst neurons.

PMID- 18718360
TI  - Eye and head torsion is affected in patients with midbrain lesions.
AB  - The midbrain has been shown to contain crucial nuclei for the control of vertical
      and torsional eye movements. Recent studies in monkeys demonstrated that midbrain
      lesions also affect head movements during gaze saccades, but so far clinical
      reports on the matter have been missing. We measured 3D eye and head movements in
      two patients with oculomotor deficits due to unilateral midbrain lesions and in
      healthy control subjects. Subjects had (1) to perform head-free target directed
      gaze saccades (head-free task), and (2) to point to the target with a head-laser
      (head-only task). The patients had vertical eye movement deficits, which were not
      compensated by the head. Three-dimensional analysis revealed torsional deviations
      from the normal range of movements for both, the eye and the head movements.

PMID- 18718361
TI  - Horizontal saccadic palsy associated with gliosis of the brainstem midline.
AB  - We studied premotor cell groups involved in the generation of saccades in a
      patient with a disturbance of voluntary horizontal gaze. The only neurological
      symptom found was a slowing of horizontal saccades, reported since birth and
      unaltered over his lifetime. We attribute this disorder, for the first time, to a
      fibrous gliosis of the brainstem midline, which may disrupt neuronal elements of
      the horizontal saccade generator crossing the brainstem midline, but it caused no
      obvious loss of omnipause-, excitatory burst-, and inhibitory burst neurons. No
      neuronal loss or demyelination, was apparent elsewhere in the brainstem; but
      there was evidence of an ependymal infection throughout the entire ventricular
      system. A diagnosis of Gaucher disease was made from the bone marrow of this
      patient shortly before his death, but for several reasons we considered this
      complication unlikely to be the cause of the saccadic disorder.

PMID- 18718362
TI  - Single versus multiple visits for endodontic treatment of permanent teeth: a
      Cochrane systematic review.
AB  - The Cochrane Collaboration promotes evidence-based healthcare decision making
      globally through systematic reviews of the effects of healthcare intervention.
      The purpose of this systematic review was to investigate whether the
      effectiveness and frequency of short-term and long-term complications are
      different when endodontic procedure is completed in one or multiple visits.
      Randomized and quasi-randomized controlled trials enrolling patients undergoing
      endodontic treatment were identified by searching biomedical databases and hand
      searching relevant journals. The following outcomes were considered: tooth
      extraction as a result of endodontic problems and radiologic failure after 1
      year, postoperative discomfort, swelling, analgesic use, or sinus track. Twelve
      studies were included in the review. No detectable difference was found in the
      effectiveness of root canal treatment in terms of radiologic success between
      single and multiple visits. Neither single-visit root canal treatment nor
      multiple-visit root canal treatment can prevent 100% of short-term and long-term
      complications. Patients undergoing a single visit might experience a slightly
      higher frequency of swelling and refer significantly more analgesic use.

PMID- 18718363
TI  - Terminal restriction fragment length polymorphism analysis of the microflora in
      necrotic teeth of patients irradiated in the head and neck region.
AB  - This study evaluated the microflora in root canals of necrotic teeth after
      radiotherapy of the head and neck region. The microbial composition of samples
      taken from necrotic root canals in patients treated with irradiation of the head
      and neck (group A, n = 13) and in healthy controls (group B, n = 11) was analyzed
      by terminal restriction fragment-length polymorphism (T-RFLP) analysis. A total
      of 50 different terminal restriction fragment lengths (T-RFs) (each representing
      one or more bacterial species) were detected in the T-RFLP profiles, 44 in group
      A and 28 in group B. A mean of 13.2 T-RFs per sample were detected in group A and
      6.6 T-RFs were present per sample for group B (p < 0.05). Twenty-two different T
      RFs (mainly subspecies of Lactobacillus spp., Capnocytophaga spp., and
      Actinomyces spp.) found in group A were not found in group B. In conclusion, the
      diversity of root canal microflora increases significantly after head-neck
      radiotherapy.

PMID- 18718364
TI  - Radiographic investigation of location and angulation of curvatures in human
      maxillary incisors.
AB  - The aim of this radiographic study was to evaluate the degree and location of
      root canal curvatures of human maxillary incisors. A total of 286 extracted human
      maxillary incisors (145 central and 141 lateral incisors) were included in this
      investigation. Exclusion criteria were teeth with extensive carious lesions,
      restorations, and root canal treatment. For this in vitro study, the teeth were
      fixed in a special device and digitally x-rayed with the parallel technique. The
      distances from the cementoenamel junction (CEJ) to the first curvature and the
      according angle were recorded. The results were analyzed descriptively, and p
      values were calculated with the Wilcoxon Mann-Whitney test. The mean distance
      between the CEJ and the first curvature of the central maxillary incisors was
      10.4 mm (standard deviation [SD] +/- 2.8) and that of the lateral incisors was
      11.1 mm (SD +/- 3.0). Most of the central incisors (right: 94.2%, left: 98.7%)
      and all of the lateral incisors exhibited curvatures. Statistically significant
      differences between central and lateral maxillary incisors could be observed
      regarding the canal curvature locations (p = 0.016) and the angle values (p <
      0.001), but there was no statistical difference between the right and the left
      side. The results showed the high percentage of root canal curvatures in
      maxillary incisors with a mean curvature located 10.7 mm apical from the CEJ.
      These findings are important to minimize failures during post insertion.

PMID- 18718365
TI  - The effect of mineral trioxide aggregate on the mineralization ability of rat
      dental pulp cells: an in vitro study.
AB  - The aim of this study was to investigate the effect of mineral trioxide aggregate
      (MTA) on cell viability and mineralization ability of rat dental pulp cells. The
      pulp capping materials, such as MTA, Dycal (Dentsply Caulk, Milford, DE), and
      Superbond C&B (SB; Sun Medical, Shiga, Japan) were placed on transwell inserts
      and cultured with rat dental pulp cells. MTA and SB exhibited no cytotoxicity,
      whereas almost all cells had died after 72 hours of culture with Dycal. MTA
      significantly stimulated mineralization by 60% compared with the control. MTA and
      Dycal significantly upregulated by two-fold the level of bone morphogenetic
      protein (BMP)-2 messenger RNA expression compared with the control. Furthermore,
      MTA increased BMP-2 protein production by about 40%, whereas Dycal significantly
      reduced it. Although MTA and Dycal increased the concentration of extracellular
      calcium by about 0.4 mmol/L, SB had no effect. These results suggest that BMP-2
      may play an important role in mineralization stimulated by MTA.

PMID- 18718366
TI  - Nicotine inhibits mineralization of human dental pulp cells.
AB  - Nicotine is a major component of tobacco smoke, and signals via nicotinic
      acetylcholine receptors (nAChR). However, little is known about the effects of
      nicotine on human dental pulp cells (HDPCs). In this study, we assessed the
      effects of nicotine on mineralization in HDPCs. We confirmed messenger RNA
      expression of nAChR subunits and examined the effects of nicotine on expression
      of extracellular matrices (ECMs), alkaline phosphatase (ALP) activity, and
      mineralized nodule formation by HDPCs. Gene expression of nAChR subunits alpha1,
      alpha2, alpha 4, alpha 5, alpha 6, alpha 7, beta1, beta2, and beta 4 was detected
      in HDPCs. Interestingly, the messenger RNA expression of dentin matrix acidic
      phosphoprotein-1, bone sialoprotein, and ALP activity were significantly reduced
      in nicotine-treated HDPC. In addition, mineralized nodule formation, which was
      examined by alizarin red staining, was also inhibited in HDPCs by the same
      treatment. These results indicate that nicotine suppresses the
      cytodifferentiation and mineralization of HDPCs, possibly via nAChR.

PMID- 18718368
TI  - The expression of macrophage and neutrophil elastases in rat periradicular
      lesions.
AB  - Macrophage elastase and neutrophil elastase are involved in tissue destruction in
      periradicular lesions. The purpose of this study was to examine these elastases
      immunohistochemically during development of periradicular lesions induced in rat
      mandibular first molar by pulpal exposure for 7, 14, 21, 28, and 42 days.
      Histologically, periapical inflammation developed from 7 to 21 days and then
      subsided after 28 days. The area of these lesions gradually increased from 7 to
      28 days and subsequently decreased at 42 days. Macrophage elastase was first
      detected at 7 days and predominantly shown from 14 to 28 days, whereas neutrophil
      elastase gradually increased from 14 to 28 days. Macrophage elastase was
      significantly greater than neutrophil elastase from 7 to 21 days. These results
      suggest that macrophage elastase was enhanced from an early stage during the
      development of these lesions and that neutrophil elastase was related to the
      expansion of periapical tissue destruction including bone resorption.

PMID- 18718367
TI  - The influence of mineral trioxide aggregate on adaptive immune responses to
      endodontic pathogens in mice.
AB  - This study assessed the influence of mineral trioxide aggregate (MTA) on adaptive
      immune responses. BALB/c mice were immunized with heat-killed Fusobacterium
      nucleatum (Fn) in MTA or other control adjuvants, and serum IgG responses to Fn
      were measured. Either Fn- or Peptostreptococcus anaerobius (Pa)-reactive memory T
      cells (Tm) were preincubated in vitro with/without MTA and restimulated with Fn
      or Pa. Tm proliferation and cytokine production were assessed. Compared with
      control groups, immunoglobulin G-antibody responses were upregulated in mice
      immunized with Fn in MTA in a similar manner to animals immunized with Fn in
      Freund's adjuvant or aluminum hydroxide adjuvant. Although MTA did not affect the
      upregulated expression of interleukin 10, tumor necrosis factor alpha, or RANKL
      by Tm, it suppressed the proliferation of Pa- or Fn-Tm and inhibited their
      production of Th1- or Th2-signature cytokines. MTA upregulated the adaptive
      humoral immune responses but had little or no effect on pro- or anti-inflammatory
      cytokine production by Tm.

PMID- 18718369
TI  - Differentially expressed protein profile of human dental pulp cells in the early
      process of odontoblast-like differentiation in vitro.
AB  - Dental pulp cells (DPCs) are capable of differentiating into odontoblasts that
      secrete reparative dentin after pulp injury. The molecular mechanisms governing
      reparative dentinogenesis are yet to be fully understood. Here we investigated
      the differential protein profile of human DPCs undergoing odontogenic induction
      for 7 days. Using two-dimensional differential gel electrophoresis coupled with
      matrix-assisted laser adsorption ionization time of flight mass spectrometry, 23
      protein spots related to the early odontogenic differentiation were identified.
      These proteins included cytoskeleton proteins, nuclear proteins, cell membrane
      bound molecules, proteins involved in matrix synthesis, and metabolic enzymes.
      The expression of four identified proteins, which were heteronuclear ribonuclear
      proteins C, annexin VI, collagen type VI, and matrilin-2, was confirmed by
      Western blot and real-time real-time polymerase chain reaction analyses. This
      study generated a proteome reference map during odontoblast-like differentiation
      of human DPCs, which will be valuable to better understand the underlying
      molecular mechanisms in odontoblast-like differentiation.

PMID- 18718370
TI  - In vitro cytotoxicity evaluation of a self-adhesive, methacrylate resin-based
      root canal sealer.
AB  - This study compared the cytotoxicity of MetaSEAL (Parkell Inc, Farmington, NY), a
      methacrylate resin-based sealer with an epoxy resin-based (AH Plus Jet; Dentsply
      Caulk, Milford, DE) and a zinc oxide-eugenol-based sealer (Pulp Canal Sealer;
      SybronEndo, Orange, CA). Five-millimeter diameter disks prepared from the
      respective sealer and disks prepared from Teflon (negative control) and
      polymethyl methacrylate (positive control) were placed in direct contact with a
      rat osteosarcoma (ROS) 17/2.8 rat osteoblast-like cell line at six intervals
      after setting completely at 72 hours and for 5 succeeding weeks after the disks
      were immersed in simulated body fluid. Succinate dehydrogenase activity was
      evaluated by using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide
      assay. All sealers exhibited severe toxicity at 72 hours, after which toxicity
      decreased gradually over the experimental period except for Pulp Canal Sealer,
      which remained severely toxic. MetaSEAL was more toxic than AH Plus Jet during
      the first week. Both were similar to the toxicity profile of the positive control
      after the first week, which was probably diffusion controlled.

PMID- 18718371
TI  - Factors affecting temperature rise on the external root surface during ultrasonic
      retrieval of intracanal separated files.
AB  - Temperature rise (TR) on the external root surface during ultrasonic removal of
      separated files (SFs) from 50 lower incisors roots of 10-mm length was
      investigated. CPR ultrasonic tips (Obtura-Spartan, Fenton, MO) were used dry to
      retrieve F2 ProTaper (Dentsply, Surrey, UK) segments fractured 2.5 mm from the
      coronal access in five groups: CPR2, CPR5, and CPR6 at power setting 1 and CPR5
      at power settings 2.5 and 5. Temperature changes were inspected at 30-second
      intervals up to 120 seconds at three different sites: two at mesiodistal and
      buccolingual surfaces adjacent to the most coronal aspect of the SF and the third
      adjacent to the most apical aspect. Overall, the highest mean TR was at the
      buccolingual root surface followed by that at the mesiodistal and the more apical
      site surfaces. At power setting 1, CPR6 produced a significantly lower TR than
      CPR5, and both can be used for 120 and 60 seconds, respectively. Power setting 5
      is not recommended for the removal of SF because this induces a hazardous TR.

PMID- 18718372
TI  - Dye extraction results on bacterial leakproof root fillings.
AB  - This study was designed to assess and compare the sensitivity and sealability
      results between bacterial leakage and dye extraction. Eighty mandibular incisors
      were prepared, and their roots were filled as follows (n = 20): G1, lateral
      condensation; G2, System B; and G3, Thermafil system. All teeth were mounted in a
      2-chamber apparatus, and the coronal access was exposed to human saliva for 100
      days. The remaining bacterial leakproof specimens were randomly assigned to
      create 3 new and equal groups (n = 10). These bacterial leakproof specimens were
      submitted to a dye extraction setup. Each specimen was placed into a plastic vial
      with 5 mL of 2% methylene blue for 48 hours. After storage, the specimens were
      rinsed with tap water and dissolved in nitric acid. A sample of 100 microL of the
      supernatant from each specimen was analyzed in a UV-Visible spectrophotometer to
      determine the amount of methylene blue leakage. The log-rank test showed no
      significant difference in the bacterial leakage pattern among the groups (P >
      .05). In the dye extraction analysis, Kruskal-Wallis H test was unable to detect
      significant differences among all experimental groups (P > .05). The 3 filling
      techniques displayed similar leakage for both leakage models. Moreover, the
      present study demonstrated that all bacterial leakproof specimens leaked when
      submitted to the blue methylene extraction model.

PMID- 18718373
TI  - The development of carbonate-containing apatite/collagen composite for
      osteoconductive apical barrier material.
AB  - The current report describes the properties of a new apical barrier material
      formulated from carbonate-containing apatite (CAp) and collagen. CAp particles of
      around 50 nm were deposited on reconstituted collagen fibers. CAp/col with about
      60 wt % CAp (corresponding to apatite content of bone) was obtained after 1 day
      of calcification. CAp content increased up to about 80 wt % in a 15-day
      calcification reaction. CAp/col was composed of fine calcified collagen fibers.
      The crystallinity and Ca/PO(4) ratio of CAp were comparable to those of bone
      apatite. The mixture of CAp/col and saline reached a pH of about 9. The optimum
      powder-to-liquid ratio (P/L) to set into a root canal was determined to be 1.2.
      Furthermore, the mixture (P/L = 1.2) condensed in a root canal was liquid
      permeable. Thus, the CAp/col was expected as an apical barrier material with
      osteoconductivity.

PMID- 18718374
TI  - Differences in aluminum equivalent values of endodontic sealers: conventional
      versus digital radiography.
AB  - The aims of this study were to compare film and digital radiography in assessing
      the radiopacities of root canal sealers and to establish the relation in aluminum
      equivalent values of different methods. Standard disks of 5 different sealers
      were exposed together with an aluminum step wedge by using occlusal films and
      storage phosphor plates. Optical density of the sealers was evaluated by
      transmission densitometry, and mean gray values were determined by digital
      analysis. The data were analyzed by using two-way analysis of variance (P = .05).
      Pairwise comparisons were made by using Tukey post hoc and paired t tests (P =
      .05). The order from the most radiopaque to the most radiolucent sealer was the
      same for both methods; however, aluminum equivalent values determined by
      transmission densitometry were significantly higher (P < .01). Aluminum
      equivalent values of the 2 radiographic methods were 7%-20% different. The
      International Standards Organization standard for the radiopacity of dental root
      canal sealing materials needs modifications for digital systems.

PMID- 18718375
TI  - An ex vivo evaluation of a gutta-percha filling technique when used with two
      endodontic sealers: analysis of the filling of main and lateral canals.
AB  - The aim of this study was to evaluate both the precision of filling and the
      extension of voids in main root canals as well as filling of lateral canals after
      using a two-phase filling technique with two sealers. Twenty-four maxillary and
      26 mandibular molars were selected and randomly assigned to two groups. Root
      canals were instrumented and then filled using the vertical compaction with the
      apical backfilling technique, with Pulp Canal Sealer (EWT) in group "A" and AH
      Plus in group "B." After clearing, voids within the filled main canals were
      measured by using a stereomicroscope. In addition, visible lateral canals were
      counted, each unfilled space was measured, and five ratings (0-4) were fixed. In
      both groups, in the most apical 4 mm of main canals, where gutta-percha was cold
      compacted, lesser voids (p <or= 0.05) were found than in the middle-coronal
      thirds backfilled with thermomechanical compaction. In group "B," more precision
      (p <or= 0.05) and lesser voids (p <or= 0.05) were found than in group "A."
      Regarding lateral canals, better filling scores (p <or= 0.05) were found in group
      "B" than in group "A." In both groups, better filling scores (p <or= 0.05) were
      found at the coronal levels than at the middle ones and at the middle levels than
      at the apical ones.

PMID- 18718376
TI  - A comparison of five radiographic systems to D-speed film in the detection of
      artificial bone lesions.
AB  - The purpose of this study was to compare three direct digital sensors (Kodak 6100
      [Rochester, NY], Schick CDR [Long Island City, NY], and Dexis PerfectSize
      [Alpharetta, GA]), a phosphor plate system (OpTime; Milwaukee, WI), and F-speed
      film to standard D-speed film in the detection of artificial bone lesions
      prepared in mandible bone sections. Artificial bone lesions were prepared at
      varying depths in the cortical bone. Radiographs were randomly presented to nine
      different observers. Logistic regression analysis indicated significant
      differences in lesion detection among the radiographic systems at the mean
      percentage of cortical bone remaining. The Kodak filtered, Schick filtered,
      OpTime unfiltered, Schick unfiltered, and Dexis filtered images were
      significantly better at lesion detection compared with D-speed film.

PMID- 18718377
TI  - Kinetics of conversion of two dual-cured adhesive systems.
AB  - The aim of this study was to evaluate the kinetics of conversion of Scotchbond
      Multi-purpose Plus (3M ESPE, St Paul, MN) and Prime&Bond NT (Dentsply De Trey,
      Konstanz, Germany) used in light-cured, self-cured, or dual-cured versions. The
      adhesive systems were used in the light-cured version (without the use of
      chemical initiator) or mixed with its respective chemical initiator either with
      light activation (dual-cured) or not (self-cured). The degree of conversion (DC)
      was monitored as a function of time during 5 minutes with a Fourier transform
      infrared spectrometer equipped with an attenuated total reflectance device. Light
      cured and dual-cured modes of Scotchbond Multi-purpose Plus presented the highest
      DC at 5 minutes. The addition of the self-cure activator (dual-cured mode) to
      Prime&Bond NT reduced the DC. For the self-cured versions, only the Scotchbond
      Multi-purpose Plus presented any polymerization reaction at 5 minutes. For the
      two bonding systems tested, it appears that light curing of the adhesive is
      important in order to reach a high DC in the first moments after the bonding
      procedure.

PMID- 18718378
TI  - Augmenting the antibiofilm efficacy of advanced noninvasive light activated
      disinfection with emulsified oxidizer and oxygen carrier.
AB  - In this study, we tested the hypothesis that the inclusion of an oxidizer and
      oxygen carrier in the photosensitization formulation would facilitate
      comprehensive disinfection of matured endodontic biofilm by light-activated
      disinfection (LAD). Photosensitizing formulations containing methylene blue (MB)
      and an oxygen carrier alone (perfluorodecahydronaphthalene) (PF1) or in
      combination with oxidizer (H(2)O(2)) (PF2) or their emulsions formed with triton
      X100 (Bio-Rad Laboratories, Hercules, CA) in different proportions (PF3 and PF4)
      were tested for photochemical properties and damage to the biofilm structure
      using confocal laser scanning microscopy. Conventional chemomechanical
      preparation, LAD using MB in water, and LAD using MB in emulsion (PF4) were also
      conducted on 10-week-old Enterococcus faecalis biofilm within root canals. MB in
      emulsion (PF4) was overall the most effective photosensitizer formulation for
      photooxidation, generation of singlet oxygen (p = 0.001), and in disinfecting
      biofilm bacteria. Advanced noninvasive LAD using a photosensitizer formulation
      containing oxidizer and oxygen carrier disrupted the biofilm matrix and
      facilitated comprehensive inactivation of biofilm bacteria. This modified
      photosensitizer formulation will have potential advantages in endodontic
      disinfection.

PMID- 18718379
TI  - Apical actinomycosis as a continuum of intraradicular and extraradicular
      infection: case report and critical review on its involvement with treatment
      failure.
AB  - This article reports a case of extraradicular actinomycosis that clearly formed a
      continuum with the intraradicular infection. Histobacteriologic and
      histopathologic analyses of the root tip and attached apical periodontitis lesion
      obtained by surgery from a tooth with persistent disease were performed to look
      for the possible reasons for persistent disease. Although no stainable bacteria
      were observed in the apparently well-treated main canal, apical ramifications
      were clogged with dense bacterial biofilms that were contiguous to extraradicular
      actinomycotic aggregates. A critical review of the literature revealed that there
      is no clear evidence that apical actinomycosis is indeed an independent entity
      leading to persistent apical periodontitis lesions.

PMID- 18718380
TI  - Mineral trioxide aggregate as repair material for furcal perforation: case
      series.
AB  - The purpose of treating furcal perforation is to seal the artificial
      communication between the endodontic space and the periradicular tissue to
      prevent alveolar bone resorption and damage to the periodontal ligament. These
      complications are not infrequent in cases of furcal and/or old perforations,
      which show a worse prognosis than fresh, small, coronal, and apical perforations.
      Mineral trioxide aggregate (MTA) is widely used to seal perforations because of
      its biocompatibility and sealability. Ten cases of furcal perforation were
      selected at the department of Endodontics, University of Florence. All the
      perforations were cleaned with NaOCl, EDTA, and ultrasonic tips and sealed with
      MTA without internal matrix. Finally, the teeth were endodontically treated and
      coronally restored. Clinical and radiographic follow-ups were done at 6 months, 1
      year, 2 years, and 5 years. After 5 years, the absence of periradicular
      radiolucent lesions, pain. and swelling along with functional tooth stability
      indicated a successful outcome of sealing perforations in 9 out of 10 teeth. One
      patient dropped out of the study after the 1-year follow-up and could not be
      contacted for further recalls. The results confirm that MTA without matrix
      provides an effective seal of root perforations and clinical healing of the
      surrounding periodontal tissue.

PMID- 18718381
TI  - Comprehensive treatment of the infected maxillary lateral incisor with an
      accessory root.
AB  - Rare anatomic anomalies may occur in the dentition and can affect treatment
      decisions and prognosis. Accurate diagnosis and therapy performed at the highest
      level can result in predictable success in these cases. This case report shows
      the clinical and radiographic findings and successful treatment (nonsurgical and
      surgical) of a combined apical and marginal periodontal inflammatory lesion of a
      maxillary lateral incisor with an accessory root.

PMID- 18718382
TI  - Management of dens invaginatus diagnosed by spiral computed tomography: a case
      report.
AB  - A thorough knowledge of the normal anatomy of the root canal system as well as
      the possible aberrancies is imperative for success of endodontic therapy. The
      challenge lies in diagnosing these conditions properly, complete debridement of
      the root canal system, and 3-dimensional sealing of the same. Conventional
      diagnostic aids like radiographs play an important role in assessment of complex
      root canal morphologies. These modalities, however, do not provide detailed
      information of the complexity as a result of their inherent limitations. This
      calls for use of more advanced imaging modalities such as spiral computed
      tomography, which can help the clinician in making a more accurate diagnosis.
      This report discusses the usefulness of spiral computed tomography in accurate
      diagnosis of a case of dens invaginatus and its successful management.

PMID- 18718383
TI  - Einstein on the train: lessons in creativity for surgeons.

PMID- 18718384
TI  - Surgically assisted palatal expansion with a bone-borne self-retaining palatal
      expander.
AB  - PURPOSE: To evaluate the use of a bone-borne self-retaining palatal expander to
      treat transverse maxillary hypoplasia in place of conventional tooth-borne
      expanders in conjunction with surgically assisted palatal expansion. PATIENTS AND
      METHODS: Ten patients with transverse maxillary hypoplasia underwent surgically
      assisted palatal expansion with insertion of a bone-borne self-retaining palatal
      expander from May 2005 to December 2006. RESULTS: All 10 patients had adequate
      transverse expansion. Nine of 10 patients had symmetric expansion. Twelve months
      postexpansion, none of the patients had transverse relapse. CONCLUSION:
      Surgically assisted palatal expansion with a bone-borne self-retaining palatal
      expander is a viable alternative to more conventional palatal expanders.

PMID- 18718385
TI  - Outcomes of total alloplastic replacement with periarticular autogenous fat
      grafting for management of reankylosis of the temporomandibular joint.
AB  - PURPOSE: The purpose of this investigation was to review the subjective,
      objective, and quality of life outcomes in a group of temporomandibular joint
      (TMJ) reankylosis patients managed by total alloplastic replacement surgery with
      a patient fitted system augmented with periarticular autogenous fat grafts to
      prevent the reformation of heterotopic bone. A review of the literature regarding
      the use of autogenous fat as evidence for its efficacy in such cases is also
      presented. PATIENTS AND METHODS: All 20 TMJ reankylosis patients (4 males, 16
      females) who had undergone total TMJ replacement with the TMJ Concepts (Ventura,
      CA) Patient-Fitted Total TMJ Prosthesis System were studied. Thirteen patients
      had bilateral, 7 unilateral for a total of 33 joint replacements. All patients
      had autogenous fat harvested from the abdomen and grafted around the articulating
      portion of the prostheses at implantation. The patients' subjective variable
      outcomes of TMJ pain, mandibular function, diet consistency, quality of life
      since the reconstruction, and objective variable of maximal interincisal opening
      were obtained in a detailed questionnaire and follow-up phone calls. RESULTS:
      Analysis of the subjective outcomes data showed improvement in reported pain,
      increased jaw function, and diet consistency. Further, a significant number of
      these patients reported improvement in their quality of life after surgery.
      Analysis of the objective outcomes data showed a significant increase in the
      maximum interincisal opening postreplacement that was maintained. CONCLUSIONS: In
      the patients followed over the course of this study, total alloplastic
      replacement with a patient-fitted prosthesis seemed to provide a safe and
      effective management for reankylosis of the TMJ. Autogenous fat transplantation
      seems to be a useful adjunct as its use seems to minimize the recurrence of joint
      heterotopic calcification, consequently providing improved and consistent range
      of mandibular motion.

PMID- 18718386
TI  - Targeted assessment of the temporomandibular joint in patients with rheumatoid
      arthritis.
AB  - PURPOSE: This observational study was done to identify the signs and symptoms of
      temporomandibular joint (TMJ) involvement in patients with rheumatoid arthritis
      (RA) and to assess the association between these and quantitative measurements
      for the evaluation of rheumatologic disease. PATIENTS AND METHODS: The sample
      comprised 61 patients suffering from RA whose signs and symptoms of TMJ were
      recorded by means of a questionnaire (scale of limited mandibular function) and
      clinical measurements (pain during jaw movement, limitation of maximal mouth
      opening, joint sounds, tenderness on TMJ palpation, tenderness on masticatory
      muscle palpation). These findings were correlated with the quantitative
      measurements for evaluating RA: duration of the disease, positivity for
      rheumatoid factor, Health Assessment Questionnaire (HAQ) score, number of
      edematous and painful joints, and overall assessment of functional status.
      RESULTS: In terms of overall figures, 70.5% of the patients presented with at
      least 1 sign or symptom, 49.2% had at least 1 symptom, and 54.1% had at least 1
      sign. The variable pain on movement was associated with the number of painful
      joints and the overall assessment findings (P < .05). Sound on movement was
      positively associated with the number of edematous joints (P = .0291). The scale
      of limited mandibular function was statistically significantly correlated with 4
      quantitative measurements (P = .0283 to .0448). The variable pain on palpation of
      the masticatory muscles was associated with the number of painful joints (P =
      .0023). Pain on palpation of the TMJ was statistically significantly associated
      with the HAQ score (P = .0344) and with the number of painful joints (P = .0006).
      CONCLUSION: A significant percentage of the patients with RA have signs and
      symptoms of TMJ involvement, and the scale of limited mandibular function proved
      to be an important measurement tool.

PMID- 18718387
TI  - Long-term stability after craniofacial distraction osteogenesis.
AB  - PURPOSE: This study was conducted to systematically review long-term skeletal
      stability after craniofacial distraction osteogenesis. MATERIALS AND METHODS:
      Several electronic databases (Old Medline, Medline, Medline In-Process and Other
      Non-Indexed Citations, Pubmed, Embase, Web of Science, and all EBM reviews
      [Cochrane Database of Systematic Reviews, ACP Journal Club, DARE, and CCTR]) were
      searched. Key words used in the search were "distraction," "osteogenesis,"
      "craniofacial," "maxillofacial," "stability," "relapse," and "recurrence." MeSH
      terms and truncations of these terms were selected with the help of a health
      science librarian. Abstracts that appeared to contain at least 3 years of
      postsurgical data were selected. The original articles were then retrieved and
      evaluated to ensure that they actually had 3 years of data after craniofacial
      distraction osteogenesis. The references were also hand-searched for possible
      missing articles that were not indexed in the searched databases. RESULTS: A
      total of 118 abstracts were found in the electronic searches. After the first set
      of selection criteria was applied on these abstracts, 22 articles were retrieved.
      After the final selection criteria were applied on these 22 articles, only 6
      articles were finally selected. These 6 articles reported long-term stability
      after craniofacial distraction osteogenesis. Sample sizes were small, and the
      methodological quality of the studies was poor. CONCLUSIONS: Although, based on
      the selected studies, craniofacial bone distraction osteogenesis appeared to show
      long-term stability; limitations of the studies merit caution in interpreting
      these findings. Some early relapse occurred in the first 3 years postdistraction,
      but stability was maintained thereafter. Some methodologically sounder studies
      are needed to confirm the present findings.

PMID- 18718388
TI  - Changes in partial pressure of arterial carbon dioxide induces redistribution of
      oral tissue blood flow in the rabbit.
AB  - PURPOSE: The purpose of this study was to investigate the effect of changes in
      partial pressure of arterial CO(2) (PaCO(2)) on oral tissue blood flow. MATERIALS
      AND METHODS: Twenty male tracheotomized Japan white rabbits were anesthetized
      with isoflurane (ISO) or propofol (PROP) under mechanical ventilation. Observed
      variables included heart rate, blood pressure, common carotid artery blood flow
      (CBF), and tissue blood flow of the mandibular bone marrow (BBF), the masseter
      muscle (MBF), and the mandibular periosteum (PBF). After completion of
      experimental preparation, CO(2) was added to inspired gas to change the inspired
      CO(2) tension. Measurements were performed with end-tidal CO(2) tension (ETCO(2))
      maintained at 30, 40, 50, and 60 mmHg. RESULTS: Heart rate in both groups
      gradually decreased with increasing ETCO(2). In contrast, both systolic and
      diastolic arterial pressures gradually increased with increasing ETCO(2). Both
      CBF and BBF increased and MBF decreased with increasing ETCO(2). PBF showed no
      change throughout the experiment. A positive relationship was observed between
      CBF and BBF; in contrast, a negative relationship was observed between CBF and
      MBF. CONCLUSION: Changes in PaCO(2) may induce a redistribution of oral tissue
      blood flow during both ISO and PROP anesthesia.

PMID- 18718389
TI  - Full-thickness lower eyelid reconstruction with a conchal chondro-perichondral
      graft and local coverage with Mio-cutaneous flaps--our divisional experience.
AB  - BACKGROUND: Eyelid reconstruction represents a challenge because of the
      complexity of this structure. Full-thickness eyelid defects demand the
      reconstruction of 2 fundamental elements: anterior and posterior lamellae. The
      available reconstructive techniques are all associated with the attention to
      restore the support and responsibility of eyelid stability, represented
      physiologically by the tarsus. In 1987, Matsuo proposed a reconstructive
      technique that involved the use of a chondro-perichondral graft harvested from
      the auricular concha to reconstruct the posterior lamella, and an adjacent skin
      flap to restore the anterior lamella. MATERIALS AND METHODS: We report our
      divisional experience of a series of 28 patients operated on from 2000 to 2004,
      whose eyelid restoration was achieved with the use of Matsuo's technique modified
      with the purpose to avoid complications such as ectropion or lagophtalmus.
      RESULTS: All the grafts survived, and no major complication such as ectropion or
      lagophthalmos has been detected. Our specialistic judgment has ranged from good
      to excellent regarding symmetry, eyelid closure, and donor site morbidity.
      Patients were entirely satisfied with the functional result obtained, and
      generally with the esthetic outcome also, judged as ranging from good to
      extremely satisfactory. CONCLUSIONS: The success of eyelid reconstruction using
      modified Matsuo's technique depends, in our minds, on an adequate knowledge of
      traditional eyelid reconstruction methods, and on a few technical fine points
      that help to reduce postoperative complications and to optimize the quality of
      the end result; hence, this technique has become the gold standard in lower
      eyelid reconstruction in our division.

PMID- 18718390
TI  - Long-term skeletal stability after maxillary advancement with distraction
      osteogenesis in nongrowing patients.
AB  - PURPOSE: We assessed the long-term skeletal stability of the repositioned
      maxilla, midface in patients who underwent maxillary advancement using
      distraction osteogenesis (DO). PATIENTS AND METHODS: The study included 19
      nongrowing patients with maxillary hypoplasia with a Class III relationship, a
      normally developed mandible, and follow-up after DO exceeding 2 years. Eleven men
      and 8 women participated, with a mean age at treatment of 20.7 years (range 15.4
      33.4 years). Twelve patients had midfacial hypoplasia associated with a cleft lip
      and palate (CLP), and 7 patients had developed noncleft-related hypoplasia. The
      surgical treatment included our modified Le Fort I osteotomy in combination with
      intraoral (5 cases) or extraoral (14 cases) distraction devices. Distraction was
      started after a latency period of 5 to 7 days and continued until the proper
      convexity was obtained. After active distraction, a 3- to 4-week period of
      retention was allowed, followed by rigid internal fixation (IF) with or without
      distractor removal. Lateral cephalometric films before midfacial distraction
      (T0), after IF with or without distractor removal (T1), 6 months after T1 (T2),
      and 2 or more years (mean 2.8 years) after T1 (T3) were analyzed. The maxillary A
      point in the Frankfort horizontal reference plane was used to assess the skeletal
      changes in the maxillary position (x, y) at each time point (T1-T3). In addition,
      we analyzed the differences in the devices and techniques. RESULTS: Midfacial DO
      was successful in all cases, resulting in a mean change obtained at point A of
      10.3 mm (8.4 mm horizontally, 4.7 mm inferiorly). Point A underwent a moderate
      amount of skeletal relapse at T2 [0.4 mm (5%) horizontally and 0.6 mm (13%)
      superiorly], with a mean of 8% (0.6 mm) horizontally and 19% (1.0 mm) superiorly
      over the mean 2.8-year (2.0-4.8 years) follow-up. After long-term follow-up, the
      maxillary advancement with DO was stable in both CLP and non-CLP patients with
      maxillary hypoplasia. In addition, our original technique using a rigid external
      device provided the most reliable results in terms of skeletal stability.
      CONCLUSION: This retrospective study showed that DO of the maxilla gives a very
      stable midface, offering a promising treatment alternative for patients with
      maxillary hypoplasia.

PMID- 18718391
TI  - Surgical management of advanced osteoarthritis of the temporomandibular joint
      with metal fossa-eminence hemijoint replacement: 10-year retrospective study.
AB  - PURPOSE: To evaluate the surgical outcomes and clinical experience of the
      treatment of degenerative osteoarthritis of the temporomandibular joint with
      metal fossa-eminence hemijoint replacement. MATERIALS AND METHODS: A
      retrospective chart review showed 99 patients (94 females and 5 males) who
      underwent treatment of degenerative joint disease with hemijoint replacement
      surgery, including data on 141 operated joints (57 unilateral, and 42 bilateral).
      A visual analog scale (VAS) patient-response questionnaire with directives was
      mailed to the 99 patients. The questionnaire investigated the patient's
      experience before and after the treatment procedure in 5 areas: 1) pain
      intensity, 2) pain experience, 3) chewing ability, 4) mouth opening, and 5) joint
      noise. In addition, patients were requested to score on a VAS of 1 to 10 their
      overall satisfaction with the treatment outcome. Treatment outcomes were also
      compared between patients who received an autogenous abdominal fat graft
      placement before wound closure, and those who did not receive this adjunctive
      treatment. RESULTS: Forty-two of 99 patients responded to the questionnaires,
      with an average follow-up time of 5.1 years. In these 42 patients, pain
      experience was reduced by 68.6% (4.5 +/- 1.3 [mean +/- SD], presurgery, vs 1.4 +/
      1.7, current, on a 6-point scale). In addition, pain intensity was reduced by
      58.7% (7.5 +/- 2.2, presurgery, vs 3.1 +/- 3.0, current, on a 10-point scale).
      Thirty-three of 42 patients (78.6%) stated in the questionnaire that they were
      highly satisfied with the results of surgical treatment (average, 9.0 +/- 1.2 on
      a 0-to-10-point VAS scale). Fifty-one patients (71 joints) did not receive an
      adjunctive abdominal fat graft, whereas 48 patients (70 joints) received this
      adjunctive treatment. In the nonfat group, 17 (21.5%) joints required revision
      surgery, and in the fat group, 4 joints (6.5%) required revision surgery.
      CONCLUSIONS: Temporomandibular hemiarthroplasty with metal fossa-eminence
      prosthesis provides predictable and satisfactory results in patients operated
      upon for advanced osteoarthritis. The incidence of revision surgery was found to
      be reduced with the application of fat graft adjunctive treatment.

PMID- 18718392
TI  - Quality of life evaluation for patients receiving vascularized versus
      nonvascularized bone graft reconstruction of segmental mandibular defects.
AB  - PURPOSE: Head and neck neoplasms requiring surgical resection of the mandible can
      have negative consequences on patient quality of life. For patients with
      segmental resections, the vascularized fibular free flap and nonvascularized
      iliac crest are frequently used. The fibula has surpassed the iliac crest in
      popularity due to the success associated with a vascularized graft; however,
      there still remain significant advantages with the nonvascularized graft. There
      has not been a study comparing the quality of life associated with these two
      methods of mandibular reconstruction. We carried out the following study to
      compare quality of life of both grafts in an attempt to help guide therapeutic
      decisions. PATIENTS AND METHODS: Twenty-nine patients at the University of
      California, San Francisco undergoing mandibular resection with subsequent
      reconstruction with either a vascularized fibular free flap or nonvascularized
      iliac crest bone graft were identified. Patient quality of life was assessed with
      a modified version of the University of Washington Quality of Life Questionnaire,
      version 4. RESULTS: Eighteen patients responded (10 reconstructed previously with
      a fibula, 8 with iliac crest reconstructions). Patients with an iliac crest bone
      graft had significantly better chewing and swallowing scores (P = .04, P = .049
      respectively). There was also a trend for better taste (P = .067). When patients
      with a history of radiation therapy were excluded, differences in chewing and
      swallowing were not significant (P = .26 and P = .31 respectively), whereas taste
      was (P = .038). CONCLUSIONS: These findings suggest that reconstruction with the
      iliac crest had benefits in improved function (chewing, swallowing, and taste)
      rather than esthetics, donor site morbidity, or psychologic discomfort as was
      anticipated. However, prior radiation, a relatively frequent therapy in this
      patient population, presents an important confounding factor. Radiation therapy
      is difficult to control for without limiting an already scarce patient pool, and
      bears with it significant morbidity that likely influenced these findings.
      Further study is warranted to confirm the results and further distinguish the 2
      groups.

PMID- 18718393
TI  - Retained third molars with orthodontics and orthognathic surgery.
AB  - PURPOSE: The aim of this study was to document the prevalence of retained third
      molars after orthodontics and orthognathic surgery. PATIENTS AND METHODS:
      Inclusion criteria for these retrospective analyses included all subjects in a
      longitudinal trial at least 18 years old at enrollment with Class II skeletal
      problems, treated presurgery with orthodontics followed by orthognathic surgery.
      Panoramic or lateral cephalometric radiographs were analyzed to assess the
      presence and relationship to the occlusal plane of third molars and the presence
      or absence of premolars, recorded at enrollment, presurgery, and postsurgery for
      each subject. The primary outcome measure was the presence of third molars
      postsurgery. Explanatory variables included third molar position at the occlusal
      plane and missing premolars. Because of the few retained third molars
      postsurgery, analyses are limited to descriptive statistics only. RESULTS: The
      majority of the 372 subjects were female (80%) and Caucasian (91%). Median age at
      enrollment was 32.3 years (interquartile range, 27.0-39.6). At entry 145 subjects
      had at least 1 third molar; 57% of third molars present were at the occlusal
      plane, and 27% of quadrants in the 145 subjects had at least 1 missing premolar.
      Sixty subjects had at least 1 third molar postsurgery, 84% of third molars
      present were at the occlusal plane, and 44% of quadrants had at least 1 missing
      premolar. CONCLUSIONS: Third molars retained after treatment for dentofacial
      deformity with orthodontics and orthognathic surgery were more likely to be at
      the occlusal plane and tended to be in quadrants with missing premolars.

PMID- 18718394
TI  - Quantitative analysis of the orbital floor defect after zygoma fracture repair.
AB  - PURPOSE: Moderate-energy zygoma fractures result frequently in a posteromedially
      displaced bone fragment. Closed reduction using a force vector directed in an
      anterolateral direction frequently produces stable repair of these injuries.
      Exploration of the orbital floor (OF) is not routinely undertaken. However, as
      the zygoma forms a significant portion of the OF, realignment may create an
      unrecognized OF defect. Routine OF exploration may be unnecessary and carries the
      risks of eyelid malposition, scarring, and extraocular muscle injury. Our goal
      was to quantitatively describe the effect of zygoma reduction on OF defect size
      and identify predictors for floor exploration. PATIENTS AND METHODS:
      Retrospectively, patients with moderate energy zygoma fractures were identified.
      Fractures inadequately reduced on the postoperative computed tomography (CT) scan
      or those which underwent OF exploration were excluded. The sizes of preoperative
      and postoperative floor defects from CT scans were measured. Globe projection was
      measured. Statistical analysis was carried out using Student's t test. RESULTS:
      Of 102 identified patients, 15 satisfied the inclusion criteria. The average pre-
      and postoperative OF defects measured 0.3 and 0.6 cm(2), respectively. This
      difference approached statistical significance, but was clinically insignificant
      except in 1 patient. Similarly, globe projection was clinically similar between
      the repaired and unaffected sides, except in the same patient. CONCLUSION: In
      majority, repair of moderate energy zygoma fractures does not clinically
      significantly increase OF defect or produce enophthalmos. In patients with
      significant displacement of the zygoma at the level of OF with comminution of
      floor fragments, the reduction maneuver may create a critical size defect and we
      believe should be followed by floor exploration.

PMID- 18718395
TI  - Prevalence and significance of human papillomavirus in oral tongue cancer: the
      Mayo Clinic experience.
AB  - PURPOSE: Cigarette smoking and alcohol use have markedly decreased in the past 40
      years. However, there has been an increasing trend in the incidence of tongue
      cancer, particularly in young patients without traditional risk factors. This
      study sought to examine the prevalence and significance of human papillomavirus
      (HPV) infection and its clinical significance in patients with oral tongue
      cancer. PATIENTS AND METHODS: Fresh-frozen tissues from 51 patients with oral
      tongue cancer, treated with primary surgery from January 2004 to December 2006,
      were included in the study. The presence of HPV infection in tumor specimens was
      analyzed by polymerase chain reaction with HPV L1 consensus primers (GP 5+/GP 6+)
      and HPV-16-specific E6 primer pairs. Demographic and clinical data were collected
      to analyze patient outcomes. RESULTS: The overall frequency of HPV in oral tongue
      cancer in our study was 1.96% (1/51). Young patients below the age of 45 years
      accounted for 15.7% (8/51) of the total number of patients. Eighty-seven percent
      of the younger age group, including a single patient with an HPV-16-positive
      tumor, were alive and free from disease during the follow-up period. The overall
      survival of the study group was 81.4%. CONCLUSIONS: Our data suggest that the
      incidence of HPV in oral tongue cancer is low and is unlikely to play a
      significant role in the etiology, pathogenesis, and clinical outcomes of oral
      tongue cancer. In addition, HPV is unlikely to constitute a significant factor in
      the rising trend of oral tongue cancer in the young population.

PMID- 18718396
TI  - Corticosteroids reduce postoperative morbidity after third molar surgery: a
      systematic review and meta-analysis.
AB  - PURPOSE: The purpose of this study was to apply meta-analytical methods to
      measure the effect of corticosteroids (CS) on edema, trismus, and pain at early
      and late postoperative periods after third molar (M3) removal. MATERIALS AND
      METHODS: A systematic search of the literature was carried out to identify
      eligible articles. The primary predictor variable was perioperative CS exposure
      (yes or no). The 3 outcome variables were edema, trismus, and pain assessed
      during the early (1-3 days) and late (>3 days) postoperative time periods.
      Standardized mean differences (SMD) for edema and weighted mean differences (WMD)
      for trismus and pain were pooled across studies. Differences between the 2
      treatment groups were assessed using random effects models and metaregressions
      for both early and late postoperative assessments. RESULTS: Twelve trials met the
      inclusion criteria. Subjects receiving CS had significantly less edema during
      both early (SMD, 1.4; 95% confidence interval [CI], 0.6, 2.2; P < .001) and late
      (SMD, 1.1; 95% CI, 0.1, 2.0; P = .03) time periods after surgery and less trismus
      than controls during the early and late postoperative periods (early WMD, 4.1 mm;
      95% CI, 2.8 mm, 5.5 mm; P < .001; late WMD, 2.7 mm; 95% CI, 0.8 mm, 4.6 mm; P =
      .005). Average pain levels were not significantly different between the 2 groups
      (early WMD, 0.4 visual analog scale [VAS]; 95% CI, -0.04 VAS, 0.9 VAS; P = .07;
      late WMD, 0.5 VAS; 95% CI, -0.6 VAS, 1.5 VAS; P = .4). CONCLUSIONS: The findings
      of this study suggest that perioperative administration of corticosteroids
      produces a mild to moderate reduction in edema and improvement in range of motion
      after M3 removal.

PMID- 18718397
TI  - Closer look at the stability of surgically assisted rapid palatal expansion.
AB  - PURPOSE: To assess the amount of dental and skeletal expansion and stability
      after surgically assisted rapid maxillary expansion (SARPE). PATIENTS AND
      METHODS: Data from 20 patients enrolled in this prospective study were collected
      before treatment, at maximum expansion, at the removal of the expander 6 months
      later, before any second surgical phase, and at the end of orthodontic treatment,
      using posteroanterior cephalograms and dental casts. RESULTS: With SARPE, the
      mean maximum expansion at the first molar was 7.48 +/- 1.39 mm, and the mean
      relapse during postsurgical orthodontics was 2.22 +/- 1.39 mm (30%). At maximum,
      a 3.49 +/- 1.37 mm skeletal expansion was obtained, and this expansion was
      stable, such that the average net expansion was 67% skeletal. CONCLUSION:
      Clinicians should anticipate a loss of about one third of the transverse dental
      expansion obtained with SARPE, although the skeletal expansion is quite stable.
      The amount of postsurgical relapse with SARPE appears quite similar to the
      changes in dental-arch dimensions after nonsurgical rapid palatal expansion, and
      also quite similar to dental-arch changes after segmental maxillary osteotomy for
      expansion.

PMID- 18718398
TI  - Policy of routine titanium miniplate removal after maxillofacial trauma.
AB  - PURPOSE: The literature shows that hardware removal rates after the fixation of
      maxillofacial fractures with miniplates are not insignificant. The aim of the
      present survey was to clarify the policies of Finnish oral and maxillofacial
      consultants for the removal of titanium miniplates after the treatment of facial
      fractures in adults. Additional aims were to clarify the factors influencing
      plate removal policy in general, and the reasons for routine plate removal in
      particular. MATERIALS AND METHODS: Twenty-six consultant oral and maxillofacial
      surgeons responded to a questionnaire about miniplate removal policy after
      treating 5 types of simple, noncomminuted fractures. RESULTS: Overall, routine
      plate removal was uncommon. However, 12 consultants (46.2%) routinely removed the
      plate after treating mandibular angle fractures, and simultaneously extracted the
      third molar because of an increased risk of infection. Most respondents (88.5%)
      stated that clinical experience guided their plate-removal policy. A policy of
      routine plate removal was most infrequent among the consultants who had the most
      experience. CONCLUSIONS: The literature provides no definitive answer to the
      question of whether routine removal of miniplates could or should be indicated,
      and in what situations. Considering the fairly significant frequency of plate
      related complications in general and infection-related complications in
      particular, long-term follow-up after treatment is indicated.

PMID- 18718399
TI  - Identification of Aspergillus species in oral tissue samples of patients with
      hematologic malignancies by in situ hybridization: a preliminary report.
AB  - PURPOSE: A definitive diagnosis of invasive oral aspergillosis can be difficult
      because the culturing of tissue samples frequently fails to isolate Aspergillus
      species. In addition, the mycelial elements of Aspergillus species seen in tissue
      sections are histopathologically indistinguishable from those of non-Aspergillus
      species. We analyzed the usefulness of a DNA probe directed against the alkaline
      proteinase (ALP) gene of Aspergillus fumigatus for the identification of
      Aspergillus species by the in situ hybridization (ISH) technique in patients with
      oral mycosis. PATIENTS AND METHODS: The ALP probe was tested on tissue specimens
      from 16 patients with hematologic malignancies who had invasive, orofacial fungal
      infections and a positive culture for one of the following organisms: Aspergillus
      species in 13 patients (A. flavus in 10, A. terreus in 2, and A. fumigatus in 1),
      and Exophiala dermatitis, Trichoderma longibrachiatum, and Candida albicans in 1
      patient each. In situ hybridization with the ALP probe was performed using
      formalin-fixed, paraffin-embedded tissue samples. RESULTS: The ALP probe showed a
      strong reaction with specimens from all 13 patients who had culture-proven
      aspergillosis specimens attributable to A. flavus, A. terreus, and A. fumigatus.
      On the other hand, the ALP probe showed no cross-reactivity with other fungi
      (Exophiala dermatitis, Trichoderma longibrachiatum, and Candida albicans).
      CONCLUSION: These findings indicate that ISH using an ALP probe may increase the
      accuracy of diagnosing invasive oral aspergillosis in immunocompromised patients,
      and facilitate the provision of adequate antifungal treatment.

PMID- 18718400
TI  - Acute proptosis in trauma: retrobulbar hemorrhage or orbital compartment syndrome
      -does it really matter?
AB  - PURPOSE: To review the nature and outcomes of acute severe proptosis in patients
      after craniofacial trauma, over a 6-year period. PATIENTS AND METHODS: These were
      identified prospectively. The mechanism of injury, nature of the proptosis, and
      visual outcomes in each case were reviewed. Review of the literature was
      undertaken. RESULTS: In all cases proptosis, was secondary to retrobulbar edema
      and not hemorrhage. CONCLUSIONS: Many cases of "retrobulbar hemorrhage" may, in
      fact, be secondary to edema. This has significant implications when managing the
      proptosed eye on an emergent basis. Possible reasons for poor outcomes are
      discussed. A number of unanswered questions arise from this review.

PMID- 18718401
TI  - Internal nasal valve: significance in nasal air flow.

PMID- 18718402
TI  - Management of transcranial orbital penetrating shrapnel/bullet war injuries.

PMID- 18718403
TI  - Treatment of human immunodeficiency virus-associated facial lipodystrophy
      syndrome with dermafat graft transfer to the nasolabial fold areas: a case report
      and review of the literature.

PMID- 18718404
TI  - Sensorineural hearing loss after dental extraction under general anesthesia:
      report of a case.

PMID- 18718405
TI  - Metastatic neuroblastoma in the mandibular condyle: report of a case.

PMID- 18718406
TI  - Persistent melanoma in situ: case report and review.

PMID- 18718407
TI  - Serotonin syndrome in the oral and maxillofacial surgery office: a review of the
      literature and report of a case.

PMID- 18718408
TI  - Oral manifestations of oxalosis: a case report and review of the literature.

PMID- 18718409
TI  - Postoperative alopecia following orthognathic surgery.

PMID- 18718411
TI  - Differentiating acute suppurative parotitis from acute exacerbation of a chronic
      parotitis: case reports.

PMID- 18718410
TI  - Myositis ossificans circumscripta of the buccinator muscle: first report of a
      rare complication of mandibular third molar extraction.

PMID- 18718412
TI  - Use of a palatal flap for torus reduction.

PMID- 18718413
TI  - Modified genioplasty and bimaxillary advancement for treating obstructive sleep
      apnea syndrome.

PMID- 18718414
TI  - A simple method for improving facial profile photographs.

PMID- 18718415
TI  - A cell stress signaling model of fetal hemoglobin induction: what doesn't kill
      red blood cells may make them stronger.
AB  - A major goal of hemoglobinopathy research is to develop treatments that correct
      the underlying molecular defects responsible for sickle cell disease and beta
      thalassemia. One approach to achieving this goal is the pharmacologic induction
      of fetal hemoglobin (HbF). This strategy is capable of inhibiting the
      polymerization of sickle hemoglobin and correcting the globin chain imbalance of
      beta-thalassemia. Despite this promise, none of the currently available HbF
      inducing agents exhibit the combination of efficacy, safety, and convenience of
      use that would make them applicable to most patients. The recent success of
      targeted drug therapies for malignant diseases suggests that this approach could
      be effective for developing optimal HbF-inducing agents. A first step in applying
      this approach is the identification of specific molecular targets. However, while
      >70 HbF-inducing agents have been described, neither molecular mechanisms nor
      target molecules have been definitively verified for any of these compounds. To
      help focus investigation in this area, we have reviewed known HbF-inducing agents
      and their proposed mechanisms of action. We find that in many cases, current
      models inadequately explain key experimental results. By integrating features of
      the erythropoietic stress model of HbF induction with data from recent
      intracellular signaling experiments, we have developed a new model that has the
      potential to explain several findings that are inconsistent with previous models
      and to unify most HbF-inducing agents under a common mechanism: cell stress
      signaling. If correct, this or related models could lead to new opportunities for
      development of targeted therapies for the beta-hemoglobinopathies.

PMID- 18718416
TI  - Bone marrow sinusoidal endothelial cells undergo nonapoptotic cell death and are
      replaced by proliferating sinusoidal cells in situ to maintain the vascular niche
      following lethal irradiation.
AB  - OBJECTIVE: Bone marrow sinusoids remain predominantly host-derived following bone
      marrow transplantation. Systematic analysis was conducted at the cellular level
      to investigate how the host sinusoidal structures survived after lethal
      irradiation. MATERIALS AND METHODS: Apoptosis and cell proliferation assays were
      performed on bone marrow sections at various time points during the first 2 weeks
      postirradiation to study the extent of damage to sinusoidal endothelial cells
      from lethal irradiation and to determine whether cell proliferation contributes
      to the recovery of the sinusoidal system. RESULTS: Phosphorylated H2AX was
      present in both hematopoietic and sinusoidal endothelial cells 3 hours after
      irradiation demonstrating DNA damage. Three days after irradiation, some
      sinusoidal endothelial cells became terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling -positive, but were caspase-3 and in situ oligo
      ligation -negative, suggesting nonapoptotic DNA fragmentation. Clusters of
      sinusoidal endothelial cells that expressed Ki67 appeared 3 days after
      irradiation, and increased through day 7. These Ki67-positive endothelial cells
      were host-derived. Bromodeoxyuridine-positive endothelial cells were present in
      the Ki67-positive areas confirming endothelial cell replication. Twenty percent
      of the sinusoidal endothelial cells were lost by day 3 after irradiation. The
      total number of endothelial cells remained relatively unchanged between day 3 and
      day 14. These results demonstrate that lethal irradiation resulted in limited,
      nonapoptotic sinusoidal endothelial cell loss, followed by proliferation of
      preexisting host-derived mature sinusoidal endothelial cells. Our data suggest
      that DNA repair mechanisms and proliferation of host endothelial cells within the
      sinusoids are involved in maintenance of the structural integrity of the bone
      marrow vascular niche following lethal irradiation.

PMID- 18718417
TI  - Preface to the special issue on redox control of cell function.

PMID- 18718418
TI  - Air pollution and cardiovascular injury epidemiology, toxicology, and mechanisms.
AB  - Recent epidemiologic studies show that increased levels of air pollutants are
      positively associated with cardiovascular morbidity and mortality. Inhalation of
      air pollutants affects heart rate, heart rate variability, blood pressure,
      vascular tone, blood coagulability, and the progression of atherosclerosis.
      Several categories within the general population (i.e., people with pre-existing
      cardiovascular disease and diabetic and elderly individuals) are considered to be
      more susceptible to air pollution-mediated cardiovascular effects. Major
      mechanisms of inhalation-mediated cardiovascular toxicity include activation of
      pro-inflammatory pathways and generation of reactive oxygen species. Although
      most studies focus on the influence of systemic effects, recent studies indicate
      that ultrafine particles may be translocated into the circulation and directly
      transported to the vasculature and heart where they can induce cardiac
      arrhythmias and decrease cardiac contractility and coronary flow.

PMID- 18718419
TI  - A randomized comparison of sirolimus- versus Paclitaxel-eluting stent
      implantation in patients with diabetes mellitus.
AB  - OBJECTIVES: The aim of this study was to compare the effectiveness of sirolimus
      eluting stents (SES) and paclitaxel-eluting stents (PES) in patients with
      diabetes mellitus (DM). BACKGROUND: Drug-eluting stent implantation significantly
      improved the angiographic and clinical outcomes compared with bare-metal stent
      implantation in diabetic patients. However, comparison of SES with PES in
      diabetic patients has not been sufficiently evaluated. METHODS: This prospective,
      multicenter, randomized study compared SES (n = 200) and PES implantation (n =
      200) for diabetic patients (n = 400). The primary end point was in-segment
      restenosis at 6 months according to intention-to-treat principle. RESULTS: The 2
      groups had similar baseline clinical and angiographic characteristics. Six-month
      in-stent (3.4% vs. 18.2%, p < 0.001) and in-segment restenosis (4.0% vs. 20.8%, p
      < 0.001) and 9-month target lesion revascularization (2.0% vs. 7.5%, p = 0.017)
      were significantly lower in the SES versus the PES group. The incidence of death
      (0% in SES vs. 0.5% in PES, p = 0.999) or myocardial infarction (0.5% in SES vs.
      0.5% in PES, p = 0.999) at 9-month follow-up was not statistically different
      between the 2 groups. Major adverse cardiac events including death, myocardial
      infarction, and target lesion revascularization at 9 months (2.0% vs. 8.0%, p =
      0.010) were lower in the SES versus the PES group. CONCLUSIONS: Sirolimus-eluting
      stent implantation is superior in reducing angiographic restenosis and improving
      9-month clinical outcomes in patients with DM and coronary artery disease
      compared with PES implantation.

PMID- 18718420
TI  - Incidence and clinical impact of dual nonresponsiveness to aspirin and
      clopidogrel in patients with drug-eluting stents.
AB  - OBJECTIVES: This study sought to determine the incidence of aspirin
      nonresponsiveness in addition to clopidogrel nonresponsiveness and whether this
      association identifies patients at an increased risk of drug-eluting stent (DES)
      thrombosis. BACKGROUND: Nonresponsiveness to clopidogrel is a predictor of DES
      thrombosis. No prospective data exist about the possible association of dual
      nonresponsiveness to clopidogrel and aspirin with DES thrombosis. METHODS:
      Platelet function was assessed after a loading dose of 600 mg clopidogrel in 746
      patients who had successful DES implantation followed by 6-month dual
      antiplatelet therapy. Platelet reactivity was assessed by light transmittance
      aggregometry using adenosine 5'-diphosphate, arachidonic acid, and collagen. The
      primary end point was definite/probable DES thrombosis at 6 months. The secondary
      end point was the composite of cardiac mortality and DES thrombosis. RESULTS: The
      incidence of dual nonresponsiveness to aspirin and clopidogrel was 6%.
      Definite/probable DES thrombosis was significantly higher in dual aspirin and
      clopidogrel nonresponders (11.1%) than in clopidogrel and aspirin responders
      (2.1%, p < 0.001), isolated clopidogrel nonresponders (2.2%, p < 0.05), or
      aspirin nonresponders (2.3%, p < 0.05). The incidence of the secondary end point
      was 4.4% in isolated clopidogrel nonresponders, 2.3% in isolated aspirin
      nonresponders, and 13.3% in dual aspirin and clopidogrel nonresponders. Dual
      clopidogrel and aspirin nonresponsiveness was an independent predictor of DES
      thrombosis (hazard ratio: 3.18, 95% confidence interval: 1.14 to 8.83, p = 0.027)
      and the composite of cardiac mortality and DES thrombosis (hazard ratio: 2.94,
      95% confidence interval: 1.16 to 7.41, p = 0.022). CONCLUSIONS: Dual
      nonresponsiveness to aspirin and clopidogrel is a relatively infrequent condition
      that identifies patients at a very high risk of DES thrombosis or death.

PMID- 18718421
TI  - Aspirin resistance an underestimated risk in patients with drug-eluting stents?

PMID- 18718422
TI  - Role of reticulated platelets and platelet size heterogeneity on platelet
      activity after dual antiplatelet therapy with aspirin and clopidogrel in patients
      with stable coronary artery disease.
AB  - OBJECTIVES: The aim of this study was to evaluate the relationship between
      reticulated platelets (RPs), platelet size, and platelet function in patients
      with stable coronary artery disease (CAD) taking aspirin and clopidogrel.
      BACKGROUND: Reticulated platelets are young platelets that are larger and
      possibly more active than non-RPs. METHODS: Flow cytometry was used to measure
      RPs after staining with thiazole orange and to define the upper 20% and lower 20%
      of platelets by size. Platelet aggregation was measured with light transmission
      aggregometry (LTA); platelet activation was assessed by measuring activated
      platelet surface expression of P-selectin and glycoprotein (GP) IIb/IIIa.
      RESULTS: Ninety patients were recruited and stratified into tertiles of %RPs.
      Patients in the upper tertile displayed greater platelet aggregation to 5-mumol/l
      adenosine diphosphate (ADP) (50.7 +/- 16.4% vs. 34.2 +/- 17.3%, p < 0.001), 1.5
      mmol/l arachidonic acid (AA) (27.3 +/- 16.9% vs. 11.7 +/- 9.3%, p < 0.001), and 1
      mug/ml collagen (18 +/- 11.6% vs. 12.1 +/- 8.7%, p < 0.05) and greater expression
      of GP IIb/IIIa (4.7 +/- 1.8% vs. 3.1 +/- 2.2%, p < 0.001). Frequency of low
      response to aspirin (AA LTA >20%) was higher in the upper tertile (53% vs. 17%, p
      < 0.001) compared with the lower tertile; low response to clopidogrel (ADP LTA
      >50%) was also elevated in the upper tertile (50% vs. 13%, p = 0.003). The larger
      platelet gate had a higher % of RPs compared with the smaller gate (15.4 +/-
      16.7% vs. 1.7 +/- 2.3%, p < 0.001) and greater GP IIb/IIIa (5.7 +/- 3.1 vs. 2.1
      +/- 1.2, p < 0.001) and P-selectin expression (7.8 +/- 4.9 vs. 4.6 +/- 2.7, p <
      0.001). CONCLUSIONS: The proportion of circulating RPs strongly correlates with
      response to antiplatelet therapy in patients with stable CAD. Large platelets
      exhibit increased reactivity despite dual antiplatelet therapy, compared with
      smaller platelets.

PMID- 18718423
TI  - Detection of soluble angiotensin-converting enzyme 2 in heart failure: insights
      into the endogenous counter-regulatory pathway of the renin-angiotensin
      aldosterone system.
AB  - OBJECTIVES: We sought to determine whether circulating soluble angiotensin
      converting enzyme 2 (sACE2) is increased in the plasma of patients with heart
      failure (HF). BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is an integral
      membrane protein that antagonizes the actions of angiotensin II and prevents the
      development of HF in animal models. However, because of the need for invasive
      cardiac tissue sampling, little is known about whether ACE2 is involved in the
      pathophysiology of HF in humans. METHODS: We developed a sensitive and specific
      assay to measure sACE2 activity in human plasma and screened a heterogeneous
      group of patients suspected of having clinical HF. RESULTS: Increasing sACE2
      plasma activity strongly correlated with a clinical diagnosis of HF (p = 0.0002),
      worsening left ventricular ejection fraction (p < 0.0001), and increasing B-type
      natriuretic peptide levels (p < 0.0001). Similar to B-type natriuretic peptide,
      sACE2 activity reflected the severity of HF, with increasing levels associated
      with worsening New York Heart Association functional class (p < 0.0001). These
      associations were independent of other disease states and medication use. We
      found that sACE2 activity was increased in patients with both ischemic and
      nonischemic cardiomyopathies and also in patients with clinical HF but a
      preserved left ventricular ejection fraction. CONCLUSIONS: Soluble ACE2 activity
      is increased in patients with HF and correlates with disease severity, suggesting
      that a cardioprotective arm of the renin-angiotensin-aldosterone system is active
      in HF.

PMID- 18718424
TI  - An ACE in the hole alternative pathways of the renin angiotensin system and their
      potential role in cardiac remodeling.

PMID- 18718426
TI  - Aortic stenosis: it is a hot topic the link to coronary artery disease.

PMID- 18718425
TI  - In vivo aortic valve thermal heterogeneity in patients with nonrheumatic aortic
      valve stenosis the: first in vivo experience in humans.
AB  - OBJECTIVES: We investigated in vivo in aortic valve stenosis (AVS) whether there
      is: 1) thermal heterogeneity within the valve leaflets; 2) temperature difference
      between the leaflets and the ascending aortic wall; and 3) a possible correlation
      between heat production, inflammation, and neoangiogenesis. BACKGROUND:
      Histological studies have demonstrated a potential role of inflammation and
      neoangiogenesis in AVS. METHODS: We examined 96 leaflets scheduled for aortic
      valve replacement. Twenty-five patients had AVS, and 7 had aortic valve
      insufficiency (AVI). Temperature measurements were performed right before
      hypothermic cardioplegia. Temperature difference (DeltaT) was assigned as the
      mean temperature of each leaflet minus the temperature of the aortic wall.
      Histological, immunohistological analysis, and vascular endothelial growth factor
      (VEGF) immunoreactivity was performed. RESULTS: Significant thermal heterogeneity
      was recorded within the leaflets of AVS, compared with AVI (1.52 +/- 1.35 degrees
      C vs. 0.13 +/- 0.11 degrees C, p < 0.01). In AVS DeltaT was greater in all
      leaflets compared with the AVI group (p < 0.01). Leaflets of AVS had increased
      inflammatory cell infiltration, calcium deposit, and anti-VEGF expression
      compared with AVI (p < 0.01). CONCLUSIONS: Thermal heterogeneity is increased in
      AVS and correlates with inflammatory mononuclear cell infiltration, expression of
      pro-inflammatory cytokines and neoangiogenic factors.

PMID- 18718427
TI  - Effect of dynamic flow rate and orifice area on mitral regurgitant stroke volume
      quantification using the proximal isovelocity surface area method.
AB  - OBJECTIVES: This study sought to determine the effect of dynamic variations of
      mitral regurgitant flow rate (MRFR) and effective regurgitant orifice area (EROA)
      on mitral regurgitant stroke volume (MRSV) quantification using 4 different
      single-point and time-integral proximal isovelocity surface area (PISA) methods
      using magnetic resonance imaging (MRI) for reference. BACKGROUND: Using PISA
      provides measures of MRFR, but calculating MRSV is challenging because of dynamic
      variations in the flow profile dependent on the underlying mechanism of mitral
      regurgitation (MR). Although various single-point and time-integral approaches
      have been described to overcome this limitation, uncertainty exists about the
      accuracy and feasibility of these methods in routine clinical practice. METHODS:
      In 73 patients with MR of different etiologies, MRSV was calculated from an
      apical 4-chamber view using the following 4 hemispheric PISA methods: 1) PISA
      velocity-time integral (VTI) = midsystolic MRFR by PISA x regurgitant flow
      VTI/peak velocity; 2) simplified PISA = midsystolic MRFR/3.25; 3) serial PISA =
      sum of instantaneous MRFRs over serial 2-dimensional frames; and 4) M-mode PISA =
      time-integral of MRFRs from color M-mode. The MRSV by MRI was calculated from
      mitral inflow minus aortic outflow. RESULTS: Single-point PISA methods yielded
      greater underestimation of MRSV (mean error: -13.3 +/- 10.2 ml [PISA-VTI]; -13.5
      +/- 10.3 ml [simplified PISA]), particularly in functional MR, compared with time
      integral PISA methods accounting for variations of MRFR and EROA over time (mean
      error: -8.0 +/- 6.4 ml [M-mode PISA]; -8.7 +/- 7.4 ml [serial PISA]).
      CONCLUSIONS: Depending on the underlying mechanism of MR, dynamic variations of
      MRFR and EROA revealed important limitations of MRSV calculation using single
      point and time-integral PISA methods.

PMID- 18718429
TI  - Frequency and predictor of coronary thin-cap fibroatheroma in patients with acute
      myocardial infarction and stable angina pectoris a 3-vessel optical coherence
      tomography study.

PMID- 18718428
TI  - Reduction in hemoglobin-oxygen affinity results in the improvement of exercise
      capacity in mice with chronic heart failure.
AB  - OBJECTIVES: This study examined whether a reduction in hemoglobin-oxygen affinity
      improves exercise capacity in mice with heart failure. BACKGROUND: Exercise
      intolerance is a major determinant of quality of life in patients with chronic
      heart failure. One of the major goals of the treatment for chronic heart failure
      is to improve quality of life. METHODS: Four weeks after left coronary ligation,
      we transplanted bone marrow cells isolated from the transgenic mice expressing a
      hemoglobin variant with low oxygen affinity, Presbyterian, into the lethally
      irradiated mice with heart failure or administered a synthetic allosteric
      modifier of hemoglobin. The mice were then exercised on a treadmill. RESULTS:
      Four weeks after the left coronary artery ligation, mice showed cardiac
      dysfunction and chamber dilation, which were characteristics of heart failure.
      The transplantation led to a reduction in hemoglobin-oxygen affinity and an
      increase in oxygen supply for skeletal muscle without changes in muscle
      properties. The transplanted mice showed improved running performance on a
      treadmill despite impaired cardiac contractility. Furthermore, administration of
      the synthetic allosteric modifier of hemoglobin showed a similar effect.
      CONCLUSIONS: Allosteric modification of hemoglobin represents a therapeutic
      option for improving exercise capacity in patients with chronic heart failure.
      One mechanism of improvement in exercise capacity is enhanced oxygen delivery in
      the skeletal muscle.

PMID- 18718430
TI  - Angioscopic comparison of neointimal coverage between zotarolimus- and sirolimus
      eluting stents.

PMID- 18718431
TI  - Adjusting clopidogrel loading doses according to vasodilator-stimulated
      phosphoprotein index: on time, too early, or too late?

PMID- 18718434
TI  - Pulmonary artery hypertension: the link between prostanoids and bloodstream
      infections.

PMID- 18718435
TI  - Strengthening infectious disease surveillance in Europe.

PMID- 18718436
TI  - Harm reduction drug policy.

PMID- 18718438
TI  - Crusaders' dysentery.

PMID- 18718439
TI  - Roel Coutinho--director of the Centre for Infectious Disease Control Netherlands.
      Interview by Marc Vandenbruaene.
AB  - In 2005, Roel Coutinho became the first director of the Netherlands' new national
      coordination centre for infectious diseases. After graduating in medicine in 1972
      from Amsterdam University, and a sojourn as a physician in tropical medicine in
      Senegal and Guinea-Bissau, Coutinho returned to the Netherlands to specialise as
      a medical microbiologist. Coutinho joined the Municipal Health Service of
      Amsterdam in 1977 as the head of the Public Health Department, where in 1984 he
      completed a PhD on sexually transmitted diseases among men who have sex with men.
      He was one of the founders of the Amsterdam cohort studies. In 1989, Coutinho was
      appointed Professor in the Epidemiology and Prevention of Infectious Diseases at
      the Academic Medical Center, University of Amsterdam. In 2000 he became General
      Director of the Municipal Health Service of Amsterdam, a post he occupied until
      joining the RIVM (National Institute for Public Health and the Environment) in
      2005. Roel Coutinho has contributed to more than 450 international publications.
      Since 2000 he has been a coeditor of the international scientific journal AIDS.
      He has two children and two grandchildren

PMID- 18718440
TI  - Comparison of antibiotics with placebo for treatment of acute sinusitis: a meta
      analysis of randomised controlled trials.
AB  - We did a meta-analysis of randomised controlled trials (RCTs) to assess the
      therapeutic role of antibiotics for acute sinusitis compared with placebo.
      Eligible studies were retrieved from PubMed and Scopus. 17 double-blind RCTs were
      included (three involving children). Acute sinusitis was diagnosed with clinical
      criteria in nine RCTs, imaging studies in six RCTs, and microbiological or
      laboratory methods in two RCTs. Amoxicillin was used in ten of 23 antibiotic
      treatment groups. To account for potential statistical heterogeneity between
      studies, a random-effects model was used for all analyses. Compared with placebo,
      antibiotics were associated with a higher rate of cure or improvement (2648
      patients, odds ratio [OR] 1.64 [95% CI 1.35-2.00], data from 16 RCTs), or cure
      alone (1813 patients, OR 1.82 [1.34-2.46], 12 RCTs), but also with more adverse
      events (1963 patients, OR 1.87 [1.21-2.90], 12 RCTs). The rate of symptom
      resolution was faster with antibiotics in most RCTs. Disease complications,
      disease recurrence, and study withdrawals because of adverse events did not
      differ between compared treatments. In conclusion, use of antibiotics for acute
      sinusitis confers a small therapeutic benefit over placebo with a corresponding
      rise in the risk for adverse events. We suggest that antibiotics should be
      reserved for carefully selected patients with a higher probability for bacterial
      disease.

PMID- 18718441
TI  - Is there any evidence that syphilis epidemics cycle?
AB  - We re-examine the evidence behind the controversial hypothesis that syphilis
      epidemics cycle. We used the same methods (spectral analysis) used by the
      proponents of this hypothesis to reanalyse a longitudinal dataset provided by the
      US Centers for Disease Control and Prevention (CDC). We also analysed a
      longitudinal CDC mortality dataset. To investigate the theoretical results
      generated by the transmission model that was used to support the hypothesis, we
      simulated the model and predicted the expected dynamics of syphilis epidemics. By
      contrast with previous findings, we found that neither of the CDC's datasets
      provides compelling evidence that syphilis epidemics cycle, and the transmission
      model (if more reasonable parameter values are used) does not predict cycling
      behaviour. We explain the possible reasons for the previous proposal that
      syphilis epidemics cycle. Our findings imply that it is quite possible that the
      CDC could be successful in eliminating syphilis within the next few decades.

PMID- 18718442
TI  - Severe atherosclerotic aortoiliac occlusive disease in a young HIV-infected
      patient.

PMID- 18718444
TI  - The cardiac ryanodine receptor: looking for anomalies in permeation properties.
AB  - Anomalies in the permeation properties of the cardiac RyR channel reconstituted
      into bilayer lipid membranes were investigated systematically. We tested the
      presence of the anomalous mole fraction effect (AMFE) for the ion conductance and
      the reversal potential with varying mole fractions of two permeant ions, while
      the total ion concentration was lower, as in previous studies, to avoid the
      masking effect of the channel pore saturation with ions. Mixtures of Ba(2+) with
      other divalents (Ca(2+), Sr(2+)), of Ca(2+) with monovalents (Li(+), Cs(+)), and
      of Na(+) with other monovalents (Cs(+), Li(+)) were used. We revealed a clear
      anomaly only for the ion conductance measured in the Na(+)-Cs(+) and Ca(2+)-Li(+)
      mixtures as computed by a Poisson-Nernst-Planck/density functional theory
      (PNP/DFT) model. Furthermore, we found a significant minimum in the concentration
      dependence of the reversal potential determined under Li(+)/Ca(2+) bi-ionic
      conditions. Our study led to new observations that may have important
      implications for understanding the mechanisms involved in ion handling in the RyR
      channel pore; furthermore our results could be useful for further validation of
      ion permeation models developed for the RyR channel.

PMID- 18718443
TI  - Oxidants and Ca+2 induce PGC-1alpha degradation through calpain.
AB  - Peroxisome proliferator activator receptor gamma coactivator 1alpha (PGC-1alpha)
      is a transcriptional coactivator known to mediate mitochondrial biogenesis.
      Whereas PGC-1alpha transcription is regulated by a variety of signaling cascades,
      the mechanisms of PGC-1alpha degradation have received less investigation. Thus,
      we investigated the mechanisms responsible for PGC-1alpha degradation in renal
      proximal tubular cells (RPTC). Amino acid sequence analysis of the PGC-1alpha
      protein revealed three PEST sequence-rich regions, predictive of proteolysis by
      calpains and/or the proteasome. Under basal conditions, treatment with the
      protein synthesis inhibitor cycloheximide resulted in rapid degradation of PGC
      1alpha (t(1/2)=38 min), which was blocked by the proteasome inhibitor epoxomicin,
      but not the calpain inhibitor calpeptin. Oxidant exposure resulted in the
      degradation of both endogenous and adenovirally over-expressed PGC-1alpha, which
      was inhibited by calpeptin but not epoxomicin. Thapsigargin-induced release of ER
      Ca(2+) also stimulated calpain-dependent, epoxomicin-independent degradation of
      PGC-1alpha. Finally, Ca(2+) addition to lysates of RPTC over-expressing PGC
      1alpha resulted in calpeptin-sensitive, epoxomicin-insensitive degradation of PGC
      1alpha. In summary, we suggest two distinct mechanisms regulate PGC-1alpha: basal
      PGC-1alpha turnover by proteasome degradation and oxidant- and Ca(2+)-mediated
      PGC-1alpha degradation through calpain.

PMID- 18718445
TI  - Comparative models of P2X2 receptor support inter-subunit ATP-binding sites.
AB  - ATP-gated P2X receptors (P2XRs) are ligand-gated ion channels (LGICs) presumably
      trimeric. To date, no experimental high-resolution structures are available.
      Recent X-ray structure of the acid-sensing ion channel 1 (ASIC1) revealed an
      unexpected trimeric ion channel. Beside their quaternary structure, P2XR and
      ASIC1 share common membrane topologies, but no significant sequence similarity.
      In order to overcome this low sequence resemblance, we have developed comparative
      models of P2X(2)R based on secondary structure predictions using the crystal
      structure of ASIC1 as template. These models were constrained to be consistent
      with known arrangement of disulfide bridges. They agreed with cross-linking
      experiments and supported inter-subunit ATP-binding sites. One of our models
      reconciled most existing data and provides new structural insights for a
      plausible mechanism of gating, thus encouraging new experiments.

PMID- 18718446
TI  - Retinoic acid inhibits osteogenic differentiation of rat bone marrow stromal
      cells.
AB  - It has been well established that all-trans-retinoic acid (ATRA) influences bone
      metabolism when given in the treatment or prevention of cancer. However, the
      molecular mechanisms underlying this are unknown. In the present study, we
      investigated the effect of ATRA on differentiation of rat bone marrow stromal
      cells (BMSCs). BMSCs were harvested from rats and induced to differentiate in the
      presence or absence of ATRA in either osteogenic (OM) or control medium (CM).
      BMSCs underwent osteogenic differentiation, showed alkaline phosphatase (ALP)
      activity, a high level of matrix mineralization, and expressed osteonectin when
      cultured in OM. Although ATRA induced ALP activity, it failed to induce matrix
      mineralization and osteonectin, decrease mineralization in OM, and induce lipid
      accumulation in BMSCs. Moreover, while ATRA induced the expression of BMP-RIA,
      both BMP-RII and Smad5 mRNA were induced by OM and ATRA. Thus, ATRA inhibited
      osteogenesis and promoted adipogenesis of BMSCs. BMP signaling cooperated with
      ATRA in the differentiation of BMSCs.

PMID- 18718447
TI  - Piezoelectric printing and probing of Lectin NanoProbeArrays for glycosylation
      analysis.
AB  - Glycans have great potential as disease biomarkers and therapeutic targets.
      However, the major challenge for glycan biomarker identification from clinical
      samples is the low abundance of key glycosylated proteins. To demonstrate the
      potential for glycan analysis with nanoliter amounts of glycoprotein, we have
      developed a new technology (Lectin NanoProbeArray) based on piezoelectric liquid
      dispensing for non-contact printing and probing of a lectin array. Instead of
      flooding the glycoprotein probe on the lectin array surface, as in conventional
      microarray screening, a piezoelectric printer is used to dispense nanoliters of
      fluorescently labeled glycoprotein probe over the lectin spots on the array. As a
      proof-of-concept, the ability of Lectin NanoProbeArrays to precisely identify and
      reliably distinguish between the closely related glycoforms of fetuin is
      illustrated here. Sensitivity levels comparable to lectin arrays that use
      evanescent-field scanners was achieved along with several orders of magnitude
      reduction in the amount of probe required for glycosylation analysis.

PMID- 18718448
TI  - Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination.
AB  - The hematopoietic-specific transcription factor p45/NF-E2 is an important
      transcriptional activator in the erythroid and megakaryocytic lineages. We
      describe the first in vivo evidence for the interaction between p45/NF-E2 and the
      E3 ubiquitin ligase Itch, and the subsequent ubiquitination of p45/NF-E2 by Itch.
      Interestingly, Itch suppressed the transactivation activity of p45/NF-E2 by
      adding a Lys63-linked polyubiquitin chain. Confocal microscopy revealed that
      ubiquitinated p45/NF-E2 became localized in the cytoplasm when Itch was over
      expressed. Thus, Itch-mediated ubiquitination of p45/NF-E2 does not target the
      protein for proteasomal degradation, but instead retains p45/NF-E2 in the
      cytoplasm, where it cannot function as a transactivator. Finally, we suggest that
      this Itch-dependent p45/NF-E2 ubiquitination mechanism may regulate NF-E2
      function during the development of hematopoietic cell lineages.

PMID- 18718449
TI  - Itch self-polyubiquitylation occurs through lysine-63 linkages.
AB  - Itch, an E3 protein ubiquitin ligase (E3), which belongs to the homologous to E6
      AP carboxy terminus (HECT)-type subfamily, catalyzes its own ubiquitylation. The
      precise nature of Itch-mediated self-modification and its biological outcome are
      not completely understood. Here, we show that Itch auto-ubiquitylation is an
      intermolecular reaction generating Lys63-linkages, rather than the Lys48-linked
      polyubiquitin chains that target proteins for proteasomal degradation. As a
      result, Itch is a relatively high stable protein, whose levels are not
      significantly affected by treatment by either proteasome or lysosome inhibitors.
      Furthermore, we demonstrate that the decay rate of a catalytic inactive Itch
      mutant, which is devoided of self-ubiquitylating activity, is barely
      indistinguishable from the one of the wild-type protein. These data definitely
      establish a nondegradative role for Lys63-linked Itch self-ubiquitylation.

PMID- 18718450
TI  - Characterization of IRA/IRB hybrid insulin receptors using bioluminescence
      resonance energy transfer.
AB  - The insulin receptor (IR) is composed of two alpha-chains that bind ligands and
      two beta-chains that possess an intracellular tyrosine kinase activity. The IR is
      expressed in cells as two isoforms containing or not exon 11 (IRB and IRA,
      respectively). Several mRNA studies have demonstrated that the two isoforms are
      co-expressed in different tissues and in several cancer cells. IRA/IRB hybrid
      receptors, constituting of an alphabeta-chain from IRA and an alphabeta-chain
      from IRB, are likely to occur in cells co-expressing both isoforms, but their
      study has been hampered by the lack of specific tools. In previous work, we used
      BRET to study IR and IGF1R homodimers and heterodimers. Here, we have used BRET
      to characterize IRA/IRB hybrids. BRET saturation experiments showed that IRA/IRB
      hybrids are randomly formed in cells. Moreover, by co-transfecting HEK-293 cells
      with a luciferase-tagged kinase-dead version of one isoform and a wild-type
      untagged version of the other isoform, we showed that IRA/IRB hybrids can
      recruit, upon ligand stimulation, a YFP-tagged intracellular partner. Finally,
      using BRET, we have studied ligand-induced conformational changes within IRA/IRB
      hybrids. Dose-response experiments showed that hybrid receptors bind IGF-2 with
      the same affinity than IRA homodimers, whereas they bind IGF-1 with a lower
      affinity. Altogether, our data indicate that IRA/IRB hybrid receptors can form in
      cells co-expressing both IR isoforms, that they are capable of recruiting
      intracellular partners upon ligand stimulation, and that they have
      pharmacological properties more similar to those of IRA than those of IRB
      homodimers with regards to IGF-2.

PMID- 18718451
TI  - Long-term depression in the superior cervical ganglion of the rat.
AB  - Long-term depression (LTD) is a use-dependent decrease in synaptic efficacy
      widely recognized as a form of synaptic plasticity related to cognitive function
      in the central nervous system. Such response has previously not been demonstrated
      in autonomic ganglia. In the isolated superior cervical ganglion (SCG) of the rat
      (superfused with Locke solution containing 100 microM choline), low-frequency
      stimulation (LFS, 3-5 Hz/15 min) of the preganglionic nerve produced a long
      lasting (up to 3 h ), significant (20-40%) decrease in the amplitude of the
      extracellularly recorded postganglionic compound action potential. Pretreatment
      of ganglia with the 5-HT(3) receptor antagonist tropisetron (0.5 microM)
      completely prevented the induction of ganglionic LTD (gLTD). Treatment of ganglia
      with the 5-HT(3) receptor antagonist MDL 72222 (0.5 microM) during the
      maintenance phase of established gLTD (1 h after LFS) antagonized the LFS-induced
      depression. Inhibition of nitric oxide (NO) synthase with l-NOARG (20-50 microM),
      applied before or after LFS, failed to affect the expression of gLTD.
      Additionally, pretreatment with the protein synthesis inhibitor emetine (1
      microM) totally prevented the expression of gLTD. However, inhibition of protein
      phosphatase with cantharidin (30 microM) did not interfere with the expression of
      gLTD. These results indicate the presence of LTD in the rat SCG and suggest that
      expression of gLTD involves activation of 5-HT(3) receptor.

PMID- 18718452
TI  - Maternal para-chlorophenylalanine exposure modifies central monoamines and
      behaviors in the adult offspring.
AB  - We reported a perspective animal model of neurodevelopmental disorders using rats
      prenatally exposed to an inhibitor of serotonin (5HT) synthesis, para
      chlorophenylalanine (PCPA). Earlier, we demonstrated that prenatal exposure to
      PCPA caused fetal 5HT depletion and changes both in open field activity and in
      depression-related behavior, as well as impairments in spatial learning in the
      adult offspring (Vataeva et al., 2007). The present study revealed that prenatal
      PCPA treatment resulted in the offspring's significantly reduced anxiety-related
      behavior in the elevated plus-maze and reduced neophobia to intake fluids in a
      novel environment. These effects are accompanied by hedonic changes in the form
      of an appropriate increase in saccharin preference. We confirmed our earlier
      finding that prenatal PCPA exposure affected the open field locomotor activity.
      In the present study we have shown that the selective 5HT reuptake inhibitor
      (SSRI) paroxetine decreases locomotor activity in the prenatally PCPA-treated
      offspring. It was also found that in the PCPA-treated fetal brain, 5HT depletion
      was associated with a significant decrease in the level of dopamine (DA)
      metabolite dihydroxyphenylacetic acid (DOPAC) and with a reduction of DOPAC/DA
      and homovanillic acid (HVA)/DA ratios. An assay of adult offspring brain revealed
      that the prenatal PCPA produced different effects on monoamines in the studied
      brain structures. The relationships between behavioral abnormalities and
      alterations in brain monoamine levels consequent on the prenatal PCPA treatment
      are discussed.

PMID- 18718453
TI  - Event-related theta and alpha oscillations mediate empathy for pain.
AB  - Our recent event-related potential (ERP) studies showed that phase-locked
      electrophysiological activities mediate both early emotional sharing and late
      cognitive evaluation during empathy for pain. However, whether non-phase-locked
      neural oscillations are involved in empathic responses remains unknown. To
      investigate the functional role of non-phase-locked theta (3-8 Hz) and alpha (9
      14 Hz) oscillations in empathy for pain, we recorded electroencephalogram (EEG)
      from healthy adults who performed pain judgment of pictures of hands in painful
      or neutral situations. Wavelet analysis was used to calculate EEG spectral power
      with high time-frequency (TF) resolution. We found that, relative to neutral
      stimuli, painful stimuli induced increased theta event-related synchronization
      (ERS) at 200-500 ms but decreased alpha event-related desynchronization (ERD) at
      200-400 ms, providing evidence for the engagement of theta and alpha activity in
      empathy for pain. In addition, subjective ratings of perceived pain and self
      unpleasantness positively correlated with theta band ERS but negatively
      correlated with alpha band ERD related to painful stimuli, suggesting that theta
      and alpha oscillations are respectively involved in emotional sharing and
      regulation during empathy for pain. Finally, the long-latency upper theta (6-8
      Hz) and alpha band TF power significantly decreased by repeated exposure to
      painful stimuli, indicating short-term adaptive changes of empathy-related neural
      activity.

PMID- 18718454
TI  - Prefrontal cortex and striatal activation by feedback in Parkinson's disease.
AB  - Positive feedbacks reinforce goal-directed behavior and evoke pleasure. In
      Parkinson's disease (PD) the striatal dysfunction impairs motor performance, but
      also may lead to decreased positive feedback (reward) processing. This study
      investigates two types of positive feedback processing (monetary feedback and
      positive informative feedback), both compared to meaningless feedback, in PD
      patients and elderly healthy controls, using fMRI. In addition, positive
      informative feedback will be compared to monetary feedback to determine whether
      positive informative feedback is just as salient as monetary feedback. Healthy
      controls showed increased activation in the left putamen during the monetary
      feedback condition compared to both the positive informative and meaningless
      feedback condition, without an effect in the medial Prefrontal Cortex (mPFC). In
      contrast, PD patients showed increased activation in the left putamen during the
      meaningless feedback condition compared to both positive feedback conditions. In
      addition, PD patients showed increased activation of the mPFC during both
      positive feedback conditions. This suggests that when confronted with positive
      feedback, the mPFC compensates for the striatal deficit. In conclusion, striatal
      activation was seen in healthy controls specifically during the monetary feedback
      condition. PD patients did not differentiate between both types of positive
      feedback. If PD patients are provided with positive feedback, the mPFC
      compensates for the striatal dysfunction. If however, PD patients are provided
      with meaningless feedback, the mPFC is less stimulated and the striatum becomes
      prominent. This study thus demonstrates striatal involvement in positive feedback
      processing and altered positive feedback processing in PD.

PMID- 18718455
TI  - Immortalized cortical neurons expressing caspase-cleaved tau are sensitized to
      endoplasmic reticulum stress induced cell death.
AB  - It has been previously reported that an Asp421 cleaved form of tau is toxic when
      expressed in cells. The purpose of this study was to understand if, and in what
      manner, the presence of Asp421 cleaved tau in neurons, which is generated by
      caspase cleavage, might facilitate neuronal death in Alzheimer's disease (AD).
      For these studies we used immortalized cortical neurons that inducibly express
      either a full-length tau isoform (T4) or an isoform that has been pseudo
      truncated at Asp421 (T4C3), to mimic caspase-3 cleavage. Neurons expressing
      either T4 or T4C3 were treated with thapsigargin, a drug, which has been shown to
      induce endoplasmic reticulum (ER) stress. Following long-term treatment with
      thapsigargin, cells expressing T4C3 presented with a marked increase in cell
      toxicity, underscored by differential activation of caspase-3 in comparison with
      cells expressing T4. Furthermore, we found that an inhibitor of the ERK1/2
      signaling pathway, which is upregulated to different extents in each cell type,
      significantly reduced toxicity in both T4 and T4C3 cells. Our results suggest
      that the presence of Asp421 cleaved tau may sensitize neurons to ER stressors and
      possibly potentiate cell death processes during AD progression.

PMID- 18718456
TI  - Dysfunction of the attentional brain network in children with Developmental
      Coordination Disorder: a fMRI study.
AB  - Children with Developmental Coordination Disorder (DCD) present impaired motor
      skills, frequently associated with impaired attentional and executive functions.
      The objective of this study was to assess the impact of DCD on effective
      connectivity applied to a putative model of inhibition. fMRI was performed in 9
      children with DCD and 10 control children (8-13 years old) performing a go-nogo
      task. As previously reported, children with DCD obtained a similar score for
      correct inhibitions as controls, but responses were slower and more variable than
      in controls. Compared to controls, Structural Equation Modeling indicated that:
      (1) path coefficients from both middle frontal cortex (MFC) and anterior
      cingulate cortex (ACC) to inferior parietal cortex (IPC) increased in children
      with DCD particularly in the left hemisphere; (2) path coefficients between
      striatum and parietal cortex decreased in children with DCD in the right
      hemisphere. Results suggest that DCD could be characterized by abnormal brain
      hemispheric specialization during development. Furthermore, connectivity in the
      MFC-ACC-IPC network could indicate that children with DCD are less able than
      healthy children to easily and/or promptly switch between go and nogo motor
      responses. However, children with DCD seem to compensate for this poor efficiency
      by more actively engaging the ACC to prevent commissions allowing maintenance of
      a good level of inhibition.

PMID- 18718457
TI  - The anti-fatty liver effects of garlic oil on acute ethanol-exposed mice.
AB  - The protective effects of single dose of garlic oil (GO) on acute ethanol-induced
      fatty liver were investigated. Mice were treated with ethanol (4.8 g/kg bw) to
      induce acute fatty liver. The liver index, the serum and hepatic triglyceride
      (TG) levels and the histological changes were examined to evaluate the protective
      effects. Hepatic malondialdehyde (MDA), glutathione (GSH) levels and superoxide
      dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GSH-Px),
      glutathione-S-transferase (GST) activities were determined for the antioxidant
      capacity assay. Acute ethanol exposure resulted in the enlargement of the liver
      index and the increase of the serum and hepatic TG levels (P<0.01), which were
      dramatically attenuated by GO pretreatment in a dose-dependent manner (P<0.01).
      GO treatment (simultaneously with ethanol exposure) exhibited similar effects to
      those of pretreatment, while no obviously protective effects were displayed when
      it was used at 2h after ethanol intake. Histological changes were paralleled to
      these indices. Beside this, GO dramatically prolonged the drunken time and
      shortened the waking time, and these effects were superior to those of silymarin
      and tea polyphenol. In addition, GO dose-dependently suppressed the elevation of
      MDA levels, restored the GSH levels and enhanced the SOD, GR and GST activities.
      Compared with the ethanol group, the MDA levels decreased by 14.2% (P<0.05),
      29.9% and 32.8% (P<0.01) in GO groups 50, 100 and 200 mg/kg, respectively. The
      GST activity increased by 9.97%, 19.94% (P<0.05) and 42.12% (P<0.01) of the
      ethanol group in GO groups 50, 100 and 200 mg/kg, respectively, while the GR
      activity increased by 28.57% (P<0.05), 37.97% (P<0.01), 50.45% (P<0.01) of the
      ethanol group in GO groups 50, 100 and 200 mg/kg, respectively. These data
      indicated that single dose of GO possessed ability to prevent acute ethanol
      induced fatty liver, but may lose its capacity when used after ethanol exposure.
      The protective effects should be associated with its antioxidative activities.

PMID- 18718458
TI  - Polyion-induced aggregation of oppositely charged liposomes and charged colloidal
      particles: the many facets of complex formation in low-density colloidal systems.
AB  - This review focusses on recent developments in the experimental study of polyion
      induced charged colloidal particle aggregation, with particular emphasis on the
      formation of cationic liposome clusters induced by the addition of anionic
      adsorbing polyions. These structures can be considered, under certain points of
      view, a new class of colloidal systems, with intriguing properties that opens
      interesting and promising new opportunities in various biotechnological
      applications. Lipidic structures of different morphologies and different
      structural complexities interacting with oppositely charged polyions give rise to
      a rich variety of self-assembled structures that present various orders of
      hierarchy in the sense that, starting from a basic level, for example a lipid
      bilayer, they arrange themselves into superstructures as, for example,
      multilamellar stacks or liquid-crystalline structures. These structures can be
      roughly divided into two classes according to the fact that the elementary
      structure, involved in building a more complex one, keeps or does not keeps its
      basic arrangement. To the first one, belong those aggregates composed by single
      structures that maintain their integrity, for example, lipidic vesicles assembled
      together by an appropriate external agent. The second one encompasses structures
      that do not resemble the ones of the original objects which form them, but,
      conversely, derive from a deep restructuring and rearrangement process, where the
      original morphology of the initial constitutive elements is completely lost. In
      this review, I will only briefly touch on higher level hierarchy structures and I
      will focus on the assembling processes involving preformed lipid bilayer vesicles
      that organize themselves into clusters, the process being induced by the
      adsorption of oppositely charged polyions. The scientific interest in polyion
      induced liposome aggregates is two-fold. On the one hand, in soft-matter physics,
      they represent an interesting colloidal system, governed by a balance between
      long-range electrostatic repulsion and short-range attraction, resulting in
      relatively large, equilibrium clusters, whose size and overall charge can be
      continuously tunable by simple environmental parameters. These structures present
      a variety of behaviors with a not yet completely understood phenomenology. On the
      other hand, the resulting structures possess some peculiar properties that
      justify their employment as drug delivery systems. Bio-compatibility, stability
      and ability to deliver various bio-active molecules and, moreover, their
      environmental responsiveness make liposome-based clusters a versatile carrier,
      with possibility of efficient targeting to different organs and tissues. Among
      the different structures made possible by the aggregating mechanism (cationic
      particles stuck together by anionic polyions or conversely anionic particles
      stuck together by cationic polyions), I will review the main experimental
      evidences for the existence of cationic liposome clusters. Especial attention is
      paid to our own work, mainly aimed at the characterization of these novel
      structures from a physical point of view.

PMID- 18718459
TI  - Recombinant IgY for improvement of immunoglobulin-based analytical applications.
AB  - OBJECTIVES: In order to provide superior tools for diagnostic approaches and to
      prevent assay interference and background binding, the objective of this study
      was the establishment and evaluation of monoclonal IgY which are phylogenetically
      distant from mammalian immunoglobulins but have been unavailable so far. DESIGN
      AND METHODS: Human, murine and avian monoclonal model antibodies were established
      and produced in mammalian cells. Their interaction with human serum components
      and Fc gamma receptors was compared by ELISA and fluorescence activated cell
      sorting (FACS). RESULTS: The use of monoclonal IgY in contrast to mammalian
      antibodies prevented interference phenomena in absorbance measurements generated
      by human sera containing rheumatoid factor (RF) or heterophilic antibodies.
      Additionally, monoclonal IgY exhibited no interaction with the human and murine
      high-affinity receptor FCGR1 (CD64) and human low affinity receptor FCGR3a
      (CD16A). CONCLUSIONS: The data obtained demonstrate the advantageous behaviour of
      monoclonal IgY as detection or capture antibodies compared to conventional
      mammalian immunoglobulins and provide a strategy for improvement of assay
      performance and accuracy.

PMID- 18718460
TI  - SKR-1, a homolog of Skp1 and a member of the SCF(SEL-10) complex, regulates sex
      determination and LIN-12/Notch signaling in C. elegans.
AB  - Sex-determination in Caenorhabditis elegans requires regulation of gene
      transcription and protein activity and stability. sel-10 encodes a WD40-repeat
      containing F-box protein that likely mediates the ubiquitin-mediated degradation
      of important sex-determination factors. Loss of sel-10 results in a mild
      masculinization of hermaphrodites, whereas dominant alleles of sel-10, such as
      sel-10(n1074), cause a more severe masculinization, including a reversal of the
      life versus death decision in sex-specific neurons. To investigate about how sel
      10 regulates sex-determination, we conducted a sel-10(n1074) suppressor screen
      and isolated a weak loss-of-function allele of skr-1, one of 21 Skp1-related
      genes in C. elegans. Skp1, Cullin, and F-box proteins, such as SEL-10, are
      components of the SCF E3 ubiquitin-ligase complex. We present genetic evidence
      that the sel-10(n1074) masculinization phenotype is dependent upon skr-1 and cul
      1 activity. Furthermore, we show that the SKR-1(M140I) weak loss-of-function
      mutation interferes with SKR-1/SEL-10 binding. Unexpectedly, we found that the
      G567E substitution in SEL-10 caused by the n1074 allele impairs the binding of
      SEL-10 to SKR-1 and the dimerization of SEL-10, which may be important for SEL-10
      function. Our results suggest that SKR-1, CUL-1 and SEL-10 constitute an SCF E3
      ligase complex that plays an important role in modulating sex-determination and
      LIN-12/Notch signaling in C. elegans.

PMID- 18718461
TI  - Signaling via the Tgf-beta type I receptor Alk5 in heart development.
AB  - Trophic factors secreted both from the endocardium and epicardium regulate
      appropriate growth of the myocardium during cardiac development. Epicardially
      derived cells play also a key role in development of the coronary vasculature.
      This process involves transformation of epithelial (epicardial) cells to
      mesenchymal cells (EMT). Similarly, a subset of endocardial cells undergoes EMT
      to form the mesenchyme of endocardial cushions, which function as primordia for
      developing valves and septa. While it has been suggested that transforming growth
      factor-betas (Tgf-beta) play an important role in induction of EMT in the avian
      epi- and endocardium, the function of Tgf-betas in corresponding mammalian
      tissues is still poorly understood. In this study, we have ablated the Tgf-beta
      type I receptor Alk5 in endo-, myo- and epicardial lineages using the Tie2-Cre,
      Nkx2.5-Cre, and Gata5-Cre driver lines, respectively. We show that while Alk5
      mediated signaling does not play a major role in the myocardium during mouse
      cardiac development, it is critically important in the endocardium for induction
      of EMT both in vitro and in vivo. Moreover, loss of epicardial Alk5-mediated
      signaling leads to disruption of cell-cell interactions between the epicardium
      and myocardium resulting in a thinned myocardium. Furthermore, epicardial cells
      lacking Alk5 fail to undergo Tgf-beta-induced EMT in vitro. Late term mutant
      embryos lacking epicardial Alk5 display defective formation of a smooth muscle
      cell layer around coronary arteries, and aberrant formation of capillary vessels
      in the myocardium suggesting that Alk5 is controlling vascular homeostasis during
      cardiogenesis. To conclude, Tgf-beta signaling via Alk5 is not required in
      myocardial cells during mammalian cardiac development, but plays an irreplaceable
      cell-autonomous role regulating cellular communication, differentiation and
      proliferation in endocardial and epicardial cells.

PMID- 18718463
TI  - The surprising complexity of the transcriptional regulation of the spdri gene
      reveals the existence of new linkages inside sea urchin's PMC and Oral Ectoderm
      Gene Regulatory Networks.
AB  - During sea urchin embryogenesis the spdri gene participates in two separate Gene
      Regulatory Networks (GRNs): the Primary Mesenchyme Cells' (PMCs) and the Oral
      Ectoderm's one. In both cases, activation of the gene follows initial
      specification events [Amore, G., Yavrouian, R., Peterson, K., Ransick, A.,
      McClay, D., Davidson, E., 2003. Spdeadringer, a sea urchin embryo gene required
      separately in skeletogenic and oral ectoderm gene regulatory networks. Dev. Biol.
      261, 55-81.]. We identified a portion of genomic DNA ("4.7IL" -3456;+389) which
      is sufficient to replicate sdpri's expression pattern in experiments of
      transgenesis, using a GFP reporter. In our experiments, the activation kinetic of
      4.7IL-GFP was similar to that of the endogenous gene and the reporter responded
      to known spdri's transcriptional regulators (Ets1, Alx1, Gsc and Dri). Here we
      present a dissection of this regulatory region and a description of the modules
      involved in spdri's transcriptional regulation. Both in the PMCs' and Oral
      Ectoderm's expression phases, activation of spdri is obtained through the
      integration of three kinds of inputs: positive and globally distributed ones;
      negative ones (that prevent ectopic expression); positive and tissue-specific
      ones. Our results allow to expand the map of the regulatory connections at the
      spdri node, both in the PMCs and in the Oral Ectoderm Gene Regulatory Networks
      (GRNs).

PMID- 18718462
TI  - Nkx genes regulate heart tube extension and exert differential effects on
      ventricular and atrial cell number.
AB  - Heart formation is a complex morphogenetic process, and perturbations in cardiac
      morphogenesis lead to congenital heart disease. NKX2-5 is a key causative gene
      associated with cardiac birth defects, presumably because of its essential roles
      during the early steps of cardiogenesis. Previous studies in model organisms
      implicate NKX2-5 homologs in numerous processes, including cardiac progenitor
      specification, progenitor proliferation, and chamber morphogenesis. By inhibiting
      function of the zebrafish NKX2-5 homologs, nkx2.5 and nkx2.7, we show that nkx
      genes are essential to establish the original dimensions of the linear heart
      tube. The nkx-deficient heart tube fails to elongate normally: its ventricular
      portion is atypically short and wide, and its atrial portion is disorganized and
      sprawling. This atrial phenotype is associated with a surplus of atrial
      cardiomyocytes, whereas ventricular cell number is normal at this stage. However,
      ventricular cell number is decreased in nkx-deficient embryos later in
      development, when cardiac chambers are emerging. Thus, we conclude that nkx genes
      regulate heart tube extension and exert differential effects on ventricular and
      atrial cell number. Our data suggest that morphogenetic errors could originate
      during early stages of heart tube assembly in patients with NKX2-5 mutations.

PMID- 18718464
TI  - Physiological levels of glutamine prevent morphine-induced preconditioning in the
      isolated rat heart.
AB  - Morphine induces cardioprotection against ischaemia-reperfusion injury. While
      aiming to investigate the underlying signal transduction cascade of morphine
      preconditioning in isolated Langendorff-perfused rat hearts, the expected
      cardioprotection was not detectable. Thus, we investigated the influence of
      different preconditioning protocols and substrate conditions on cardioprotection
      in this experimental model. Isolated rat hearts underwent 35 min global ischaemia
      followed by 60 min reperfusion. Morphine PC was initiated by 3 cycles of 5 min 1
      muM morphine with either 5 min washout [3PC5 (5)] or 15 min washout [3PC5 (15)]
      before ischaemia; by 15 min morphine with 15 min washout before ischaemia [PC15
      (15)]; or by 15 min 10 muM morphine with 15 min washout [PC15 (15)-10 microM].
      Ischaemic preconditioning was initiated by 3 cycles of 3 min ischaemia; in
      another group, hearts received 1 muM morphine continuously for 10 min before
      ischaemia until the end of reperfusion [continued morphine]. To investigate the
      effects of glutamine, two groups received a glutamine-free perfusate: a control
      group, and a morphine preconditioning group [3PC5 (15)]. Ischaemic
      preconditioning reduced infarct size by 75%, and continued morphine by 46%
      compared to control group. With the glutamine containing perfusate, none of the
      morphine PC pretreatments had an effect on infarct size. In glutamine-free
      perfusate, 3 cycles of 5 min 1 microM morphine with 15 min washout reduced
      infarct size from 45%+/-8% (control) to 20%+/-5% (3PC5 (15). Cardioprotection by
      morphine-induced preconditioning is model dependent: in the isolated rat heart,
      morphine preconditioning is prevented by a glutamine containing perfusate.

PMID- 18718465
TI  - Heterotypic contact reveals a COX-2-mediated suppression of osteoblast
      differentiation by endothelial cells: A negative modulatory role for prostanoids
      in VEGF-mediated cell: cell communication?
AB  - In bone, angiogenesis must be initiated appropriately, but limited once
      remodelling or repair is complete. Our recent findings have supported a role for
      prostaglandins (PG), known modulators of osteoblast (OB) and endothelial cell
      (EC) behaviour, in facilitating VEGF-mediated paracrine communication from OBs to
      'remotely located' ECs, but the mechanism(s) regulating OB:EC crosstalk when
      these cells are closely opposed are undefined. In this study we have examined:
      (i) the effects of exogenous PGE(2) on VEGF-driven events in ECs, and (ii) the
      role of endogenous COX-2-derived prostanoids in mediating communication between
      intimately opposed OBs and ECs in direct contact. Exposure of ECs to PGE(2)
      increased ERK1/2 phosphorylation, COX-2 induction, 6-keto-PGF(1alpha) release and
      EC proliferation. In contrast, PGE(2) attenuated VEGF(165)-induced VEGFR2/Flk1
      phosphorylation, ERK1/2 activation and proliferation of ECs, suggesting that
      exogenous PGE(2) restricts the actions of VEGF. However, the COX-2-selective
      inhibitor, NS398, also attenuated VEGF-induced proliferation, implying a distinct
      role for endogenous COX-2 activity in regulating EC behaviour. To examine the
      effect of OB:EC proximity and the role of COX-2 products further, we used a
      confrontational co-culture model. These studies showed that COX-2 blockade with
      NS398 enhanced EC-dependent increases in OB differentiation, that this effect was
      reversed by exogenous PGH(2) (immediate COX-2 product), and that exogenous VEGF
      did not influence EC-dependent OB differentiation under these conditions. Our
      findings indicate that locally produced prostanoids may serve distinct roles
      depending on OB:EC proximity and negatively modulate VEGF-mediated changes in EC
      behaviour when these cells are closely opposed to control angiogenesis during
      bone (re)modelling.

PMID- 18718466
TI  - YIPF5 and YIF1A recycle between the ER and the Golgi apparatus and are involved
      in the maintenance of the Golgi structure.
AB  - Yip1p/Yif1p family proteins are five-span transmembrane proteins localized in the
      Golgi apparatus and the ER. There are nine family members in humans, and YIPF5
      and YIF1A are the human orthologs of budding yeast Yip1p and Yif1p, respectively.
      We raised antisera against YIPF5 and YIF1A and examined the localization of
      endogenous proteins in HeLa cells. Immunofluorescence, immunoelectron microscopy
      and subcellular fractionation analysis suggested that YIPF5 and YIF1A are not
      restricted to ER exit sites but also localized in the ER-Golgi intermediate
      compartment (ERGIC) and some in the cis-Golgi at steady state. Along with
      ERGIC53, YIPF5 and YIF1A remained in the cytoplasmic punctate structures after
      brefeldin A treatment, accumulated in the ERGIC and the cis-Golgi after treatment
      with AlF4- and accumulated in the ER when ER to Golgi transport was inhibited by
      Sar1(H79G). These results supported the localization of YIPF5 and YIF1A in the
      ERGIC and the cis-Golgi, and strongly suggested that they are recycling between
      the ER and the Golgi apparatus. Analysis by blue native PAGE and co
      immunoprecipitation showed that YIPF5 and YIF1A form stable complexes of three
      different sizes. Interestingly, the knockdown of YIPF5 or YIF1A caused partial
      disassembly of the Golgi apparatus suggesting that YIPF5 and YIF1A are involved
      in the maintenance of the Golgi structure.

PMID- 18718468
TI  - Treatment with edaravone, initiated at symptom onset, slows motor decline and
      decreases SOD1 deposition in ALS mice.
AB  - Edaravone is a free-radical scavenger, an agent being widely used for cerebral
      ischemia in Japan. To evaluate its efficacy for possible treatment of amyotrophic
      lateral sclerosis (ALS), we performed a randomized blind trial in ALS model mice.
      After identification of the clinical onset in each female G93A mutant SOD1
      transgenic mouse, we intraperitoneally administered multiple doses of edaravone
      to the mice and observed their motor symptoms. We also counted the number of
      lumbar motoneurons, determined the 3-nitrotyrosine/tyrosine ratio, and evaluated
      the abnormal SOD1 aggregation in the spinal cord at the 10th day after the
      edaravone injection. Edaravone significantly slowed the motor decline of the
      transgenic mice. The remaining motoneurons were significantly preserved in the
      higher-dose edaravone-administered group, and the 3-nitrotyrosine/tyrosine ratios
      were reduced dose-dependently. Intriguingly, the area of abnormal SOD1 deposition
      in the spinal cord was significantly decreased in the higher-dose edaravone
      administered group. Our results indicate that edaravone was effective to slow
      symptom progression and motor neuron degeneration in the ALS model mice. These
      favorable actions might be attributable to the yet unidentified mechanism
      responsible for reducing the deposition of mutant SOD1.

PMID- 18718467
TI  - Characterization of Muller glia and neuronal progenitors during adult zebrafish
      retinal regeneration.
AB  - The adult zebrafish retina exhibits a robust regenerative response following
      light-induced photoreceptor cell death. This response is initiated by the Muller
      glia proliferating in the inner nuclear layer (INL), which gives rise to neuronal
      progenitor cells that continue to divide and migrate to the outer nuclear layer
      (ONL), where they differentiate into rod and cone photoreceptors. We previously
      conducted a microarray analysis of retinal gene expression at 16, 31, 51, 68, and
      96 h of constant intense-light treatment to identify genes and their
      corresponding proteins that may be involved in the generation and proliferation
      of the neuronal progenitor cells. We examined the expression of two candidate
      transcription factors, Pax6 and Ngn1, and one candidate transgene, olig2:EGFP, in
      the regenerating light-damaged retina. We compared the temporal and spatial
      expression patterns of these markers relative to PCNA (proliferating cell nuclear
      antigen), an established marker for proliferating cells in the zebrafish retina,
      and the Tg(gfap:EGFP) nt11 transgenic line that specifically labels Muller glial
      cells. We found that Muller glial cells dedifferentiate during regeneration,
      based on the loss of cell-specific markers such as GFAP (glial fibrillary acidic
      protein) and glutamine synthetase following their reentry into the cell cycle to
      produce neuronal progenitors. Pax6 expression was first detected in the
      proliferating neuronal progenitors by 51 h of constant light treatment, which is
      significantly after the Muller glia first reenter the cell cycle after 31h of
      light. This suggests that Pax6 expression increases in neuronal progenitors,
      rather than in the proliferating Muller glia. EGFP expression from the olig2
      promoter was first detected by 68 h of constant light treatment in the
      dedifferentiated Muller glia, with Pax6 expressed in the closely associated
      proliferating neuronal progenitors migrating to the ONL. Both Pax6 and olig2
      expression persisted until 3 days post-light treatment, when the neuronal
      progenitors begin differentiating into new rod and cone photoreceptors. Ngn1
      protein expression was initially detected in proliferating neuronal progenitors
      at 68 h of light treatment. However, Ngn1 expression persisted in a subset of the
      INL nuclei until 17 days post-light treatment. Using the Tg(gfap:EGFP) nt11
      transgenic line, Ngn1 was localized to the Muller glial nuclei that were
      reestablished following the regenerative response. These markers, therefore, can
      be used to identify different cell types at particular stages of retinal
      regeneration: neuronal progenitor formation, proliferation, and the
      reestablishment of the Muller glia cells. These markers will be important to
      further characterize the regeneration response in other retinal damage models and
      to elucidate the defects associated with mutants and morphants that disrupt the
      regeneration response.

PMID- 18718469
TI  - Are two leads always better than one: an emerging case for unilateral subthalamic
      deep brain stimulation in Parkinson's disease.
AB  - Bilateral subthalamic (STN) deep brain stimulation (DBS) provides significant
      symptom relief for the majority of well-screened patients suffering with
      Parkinson's disease (PD). Implantation of stimulating electrodes bilaterally in a
      single session has become standard in most operating theaters worldwide. There
      is, however, limited evidence-based support for this approach. Although bilateral
      surgical procedures have been shown, using standardized clinical ratings, to
      provide greater motor benefits compared to unilateral procedures, bilateral
      procedures are more likely to be associated with increased acute and long-term
      complications including post-operative confusion, speech difficulties and
      cognitive dysfunction. Unilateral stimulation has been shown to provide
      significant benefits for appendicular and axial symptoms. The relative benefit of
      implanting one versus two sides and whether the degree of benefit associated with
      the second side is worth the potential risk of doing so have not been examined
      systematically. The relative magnitude of benefit associated with unilateral
      versus bilateral procedures is likely to vary from patient to patient,
      particularly in those patients with asymmetric symptomatology. As such, there are
      likely subsets of patients who do not require and therefore should not be exposed
      to the potential complications associated with bilateral simultaneous
      implantation. This review and commentary will outline our current understanding
      of the benefits associated with unilateral and bilateral STN DBS and discuss the
      role of unilateral or staged unilateral procedures as an alternative surgical
      approach for patients with advanced PD.

PMID- 18718470
TI  - Dopamine acting through D2 receptors modulates the expression of PSA-NCAM, a
      molecule related to neuronal structural plasticity, in the medial prefrontal
      cortex of adult rats.
AB  - A "neuroplastic" hypothesis proposes that changes in neuronal structural
      plasticity may underlie the aetiology of depression and the action of
      antidepressants. The medial prefrontal cortex (mPFC) is affected by this disorder
      and shows an intense expression of the polysialylated form of the neural cell
      adhesion molecule (PSA-NCAM), a plasticity-associated molecule, which is
      expressed mainly in interneurons. The monoamines serotonin, dopamine and
      noradrenaline are the principal targets of antidepressant action. Pharmacological
      manipulation of serotonin levels regulates synaptophysin and PSA-NCAM expression
      in the adult mPFC. However, the involvement of structural plasticity on the
      antidepressant effects of dopamine has not been well explored yet. Using
      immunohistochemistry, we have studied the relationship between dopaminergic
      fibers and PSA-NCAM expressing neurons in the mPFC and the expression of D2
      receptors. In order to evaluate the effects of dopamine in neuronal structural
      plasticity and on inhibitory neurotransmission, we have analyzed the expression
      of synaptophysin, PSA-NCAM and GAD67 in the mPFC after cortical dopamine
      depletion with 6-OHDA and after chronic treatments with the D2 receptor
      antagonist haloperidol or the D2 receptor agonist PPHT. Many dopaminergic fibers
      were observed in close apposition to PSA-NCAM expressing neurons and 76% of these
      cells co-expressed D2 receptor. Both haloperidol treatment and 6-OHDA injection
      reduced significantly PSA-NCAM, synaptophysin and GAD67 expression in the mPFC.
      Conversely, PPHT treatment increased the expression of these molecules. Our
      results give support to the "neuroplastic" hypothesis of depression, suggesting
      that dopamine acting on D2 receptors may modulate neuronal structural plasticity
      and inhibitory neurotransmission through changes in PSA-NCAM expression.

PMID- 18718471
TI  - Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with
      nonalcoholic steatohepatitis.
AB  - BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is a leading cause of
      chronic liver disease for which there is limited therapy available. Insulin
      sensitizing, anti-inflammatory, and antifibrotic properties of thiazolidinediones
      support their use in treating NASH. We have evaluated pioglitazone in the
      treatment of nondiabetic patients with NASH. METHODS: We randomized 74
      nondiabetic patients (45 men; median age, 54 y) with histologically proven NASH
      to 12 months of standard diet, exercise, and either placebo or pioglitazone (30
      mg/day). Sixty-one patients (30 placebo, 31 pioglitazone) had liver biopsies both
      at the beginning and the end of the study. RESULTS: Compared with placebo,
      pioglitazone therapy was associated with an increase in weight (mean change, 
      0.55 vs +2.77 kg; P = .04) and a reduction in glucose (+0.4 vs -0.1 mmol/L; P =
      .02), HbA1c (+0.16% vs -0.18%; P = .006), insulin C peptide level (+42 vs -78
      pmol/L; P = .02), alanine aminotransferase level (-10.9 vs -36.2 u/L; P = .009),
      gamma-glutamyltransferase level (-9.4 vs -41.2 u/L; P = .002), and ferritin (
      11.3 vs -90.5 microg/L; P = .01). Histologic features including hepatocellular
      injury (P = .005), Mallory-Denk bodies (P = .004), and fibrosis (P = .05) were
      reduced in patients treated with pioglitazone compared with those in the placebo
      group. CONCLUSIONS: Pioglitazone therapy over a 12-month period in nondiabetic
      subjects with NASH resulted in improvements in metabolic and histologic
      parameters, most notably liver injury and fibrosis. Larger extended trials are
      justified to assess the long-term efficacy of pioglitazone in this patient group.

PMID- 18718472
TI  - Sex-associated differences in the leptin and ghrelin systems related with the
      induction of hyperphagia under high-fat diet exposure in rats.
AB  - Leptin and ghrelin are known to be main hormones involved in the control of food
      intake, with opposing effects. Here we have explored whether changes in the
      leptin and ghrelin system are involved in the long-term effects of high-fat (HF)
      diet feeding in rats and whether sex-associated differences exist. Male and
      female Wistar rats were fed until the age of 6 months with a normal-fat (NF) or
      an HF-diet. Food intake and body weight were followed. Gastric and serum levels
      of leptin and ghrelin, and mRNA levels of leptin (in stomach and adipose tissue),
      ghrelin (in stomach), and NPY, POMC, and leptin and ghrelin receptors (OB-Rb and
      GHS-R) (in the hypothalamus) were measured. In both males and females, total
      caloric intake and body weight were greater under the HF-diet feeding. In
      females, circulating ghrelin levels and leptin mRNA expression in the stomach
      were higher under HF-diet. HF-diet feeding also resulted in higher hypothalamic
      NPY/POMC mRNA levels, more marked in females, and in lower OB-Rb mRNA levels,
      more marked in males. In addition, in females, serum ghrelin levels correlated
      positively with hypothalamic NPY mRNA levels, and these with caloric intake. In
      males, hypothalamic OB-Rb mRNA levels correlated positively with POMC mRNA levels
      and these correlated negatively with caloric intake and with body weight. These
      data reflect differences between sexes in the effects of HF-diet feeding on food
      intake control systems, suggesting an impairment of the anorexigenic leptin-POMC
      system in males and an over-stimulation of the orexigenic ghrelin-NPY system in
      females.

PMID- 18718473
TI  - Stable transfection of Eimeria tenella: constitutive expression of the YFP-YFP
      molecule throughout the life cycle.
AB  - The obligate intracellular apicomplexan parasite Eimeria tenella, one of seven
      species of Eimeria that infect chickens, elicits protective cell-mediated
      immunity against challenge infection. For this reason, recombinant E. tenella
      parasites could be utilised as an effective vaccine vehicle for expressing
      foreign antigens and inducing immunity against heterologous intracellular
      microbes. A stable line of E. tenella expressing foreign genes is a prerequisite,
      and in this work an in vivo stable transfection system has been developed for
      this parasite using restriction enzyme-mediated integration (REMI). Two
      transgenic populations of E. tenella have been obtained that express YFP-YFP
      constitutively throughout the parasite life cycle. Southern blotting and plasmid
      rescue analyses show that the introduced exogenous DNA was integrated at random
      into the parasite genome. Although the life cycle of the transgenic populations
      was delayed by at least 12h and the output of oocysts was reduced 4-fold relative
      to the parental BJ strain of E. tenella, the transgenic parasites were
      sufficiently immunogenic to protect chickens against challenge with either
      transgenic or parental parasites. These results are encouraging for the
      development of transgenic E. tenella as a vaccine vector and for more detailed
      investigation of the biology of the genus Eimeria.

PMID- 18718474
TI  - Legumains from the hard tick Haemaphysalis longicornis play modulatory roles in
      blood feeding and gut cellular remodelling and impact on embryogenesis.
AB  - The biology and vectorial capacity of haematophagous ticks are directly related
      to effective blood feeding and digestion. The midgut-associated proteases in
      ticks are involved in the blood (Hb) digestion cascade, the molecular mechanisms
      of which are yet poorly understood. Our previous studies indicated that
      Haemaphysalis longicornis midgut-specific asparaginyl endopeptidases/legumains,
      HlLgm and HlLgm2, act in the Hb digestion cascade. Here, we investigated the
      potential of these enzymes in blood feeding and digestion, midgut remodelling and
      reproduction of ticks by employing RNA interference (RNAi) techniques. Injection
      of HlLgm- and HlLgm2 gene-specific double-stranded RNAs into unfed adult female
      H. longicornis caused gene-specific transcriptional and translational
      disruptions. RNAi impacted on tick blood feeding leading to death of the feeding
      ticks, failure of ticks to reach repletion and significant reductions in engorged
      tick body weight. Histological examination revealed that deletion of legumains
      resulted in damage to the midgut tissues and disruption of normal cellular
      remodelling during feeding. Gene knock-down also caused significantly delayed
      onset of oviposition, reduced number of eggs and, most strikingly, structurally
      deformed eggs that failed to hatch suggesting imperfect embryogenesis.
      Synergistic impacts of RNAi were reflected on all parameters evaluated when HlLgm
      and HlLgm2 were silenced together. These findings suggest that legumains may play
      modulatory roles in blood feeding and digestion, midgut cellular remodelling and
      embryogenesis in H. longicornis. Deletion of legumains in H. longicornis would
      help in controlling the tick population and thereby transmission of diseases to
      their hosts.

PMID- 18718475
TI  - The rat heart contains a neural stem cell population; role in sympathetic
      sprouting and angiogenesis.
AB  - Nestin-expressing cells were identified in the normal rat heart characterized by
      a small cell body and numerous processes and following an ischemic insult
      migrated to the infarct region. The present study was undertaken to identify the
      phenotype, origin and biological role of nestin-expressing cells during
      reparative fibrosis. A neural stem cell phenotype was identified based on musashi
      1 expression, growth as a neurosphere, and differentiation to a neuronal cell.
      Using the Wnt1-cre; Z/EG transgenic mouse model, which expresses EGFP in
      embryologically-derived neural crest cells, the reporter signal was detected in
      nestin-expressing cells residing in the heart. In infarcted human hearts, nestin
      expressing cells were detected in the viable myocardium and the scar and
      morphologically analogous to the population identified in the rat heart.
      Following either an ischemic insult or the acute administration of 6
      hydroxydopamine, sympathetic sprouting was dependent on the physical association
      of neurofilament-M immunoreactive fibres with nestin-positive processes emanating
      from neural stem cells. To specifically study the biological role of the
      subpopulation in the infarct region, neural stem cells were isolated from the
      scar, fluorescently labelled and transplanted in the heart of 3-day post-MI rats.
      Injected scar-derived neural stem cells migrated to the infarct region and were
      used as a substrate for de novo blood vessel formation. These data have
      demonstrated that the heart contains a resident population of neural stem cells
      derived from the neural crest and participate in reparative fibrosis. Their
      manipulation could provide an alternative approach to ameliorate the healing
      process following ischemic injury.

PMID- 18718476
TI  - Cyclin towards infarction!

PMID- 18718477
TI  - Elucidating the protein cold-adaptation: Investigation of the parameters
      enhancing protein psychrophilicity.
AB  - To investigate the role of the critical parameters in adaptation of proteins to
      low temperatures, a comparative systematic analysis was performed. Several
      parameters were proposed to have contribution to cold adaptation of proteins.
      Among proposed parameters, total values of residual structure states, secondary
      structure states and oligomeric states were alike in both psychrophilic and
      mesophilic proteins. In addition, our results provided new quantitative
      information about the trends in the substitution preference of Ile, Phe, Tyr,
      Lys, Arg, His, Glu and Leu with most of amino acids and substitution avoidance of
      Gly, Thr and Ala with most of amino acids. These findings would help future
      efforts propose a strategy for designing psychrophilic proteins.

PMID- 18718478
TI  - Ozagrel reverses streptozotocin-induced constriction of arterioles in rat retina.
AB  - Retinal blood flow decreases early in the progression of diabetic retinopathy;
      however, the mediators and mechanisms responsible for this decrease have yet to
      be determined. In this study, diabetes was induced by streptozotocin in rats, and
      retinal blood flow was measured via intravital microscopy 1 or 3 weeks following
      the induction of hyperglycemia. Additionally, retinal arteriolar diameters and
      flow were measured prior to and following acute administration of the thromboxane
      synthase inhibitor ozagrel to investigate the potential role of thromboxane in
      the observed constriction. Minimal changes in the retinal diameters and flow were
      observed at 1 week of diabetes; however, at 3 weeks of diabetes, arteriolar
      constriction and decreases in blood flow were significant. Notably, the
      constriction occurred only in the arterioles that were in closer proximity to the
      venules draining the retina. Acute administration of ozagrel reversed the
      constriction of the closely venule-paired arterioles. In summary, the results
      suggest that thromboxane mediates localized, venule-dependent arteriolar
      constriction induced by streptozotocin-induced diabetes in rats.

PMID- 18718479
TI  - A critical role of Rho-kinase ROCK2 in the regulation of spine and synaptic
      function.
AB  - The actin cytoskeleton is critically involved in the regulation of the dendritic
      spine and synaptic properties, but the molecular mechanisms underlying actin
      dynamics in neurons are poorly defined. We took genetic approaches to create and
      analyze knockout mice specifically lacking ROCK2, a protein kinase that directly
      interacts with and is activated by the Rho GTPases, the central mediator of actin
      reorganization. We demonstrated that while these knockout mice were normal in
      gross brain anatomy, they were impaired in both basal synaptic transmission and
      hippocampal long-term potentiation (LTP). Consistent with the
      electrophysiological deficits, the ROCK2 knockout neurons showed deficits in
      spine properties, synapse density, the actin cytoskeleton, and the actin-binding
      protein cofilin. These results indicate that ROCK2/cofilin signaling is critical
      in the regulation of neuronal actin, spine morphology and synaptic function.

PMID- 18718480
TI  - Opioid receptors: from binding sites to visible molecules in vivo.
AB  - Opioid drugs such as heroin interact directly with opioid receptors whilst other
      addictive drugs, including marijuana, alcohol and nicotine indirectly activate
      endogenous opioid systems to contribute to their rewarding properties. The opioid
      system therefore plays a key role in addiction neurobiology and continues to be a
      primary focus for NIDA-supported research. Opioid receptors and their peptide
      ligands, the endorphins and enkephalins, form an extensive heterogeneous network
      throughout the central and peripheral nervous system. In addition to reward,
      opioid drugs regulate many functions such that opioid receptors are targets of
      choice in several physiological, neurological and psychiatric disorders. Because
      of the multiplicity and diversity of ligands and receptors, opioid receptors have
      served as an optimal model for G protein coupled receptor (GPCR) research. The
      isolation of opioid receptor genes opened the way to molecular manipulations of
      the receptors, both in artificial systems and in vivo, contributing to our
      current understanding of the diversity of opioid receptor biology at the
      behavioral, cellular and molecular levels. This review will briefly summarize
      some aspects of current knowledge that has accumulated since the very early
      characterization of opioid receptor genes. Importantly, we will identify a number
      of research directions that are likely to develop during the next decade.

PMID- 18718481
TI  - Isolation and characterization of ellagic acid derivatives isolated from Casearia
      sylvestris SW aqueous extract with anti-PLA(2) activity.
AB  - The Casearia sylvestris SW (Flacourtiaceae) is utilized in folk medicine (Brazil
      and all Latin American) to treat several pathologic processes as inflammation,
      cancer, microbial infection and snake bites. Studies showed that C. sylvestris
      aqueous extract can inhibit many toxic effects caused by snake venoms (or caused
      by phospholipase A(2) isolated) from different species, mainly of Bothrops genus.
      Inhibition of enzymatic and myotoxic activities, decrease of edema formation and
      increase of the survival rate of rats injected with lethal doses of bothropic
      venoms are some toxic effects inhibited by C. sylvestris. In this study, four
      ellagic acid derivatives from aqueous extracts of C. sylvestris were isolated,
      characterized, and tested against effects from both total venom and PLA(2) (Asp
      49 BthTX-II) from the venom of Bothrops jararacussu. The isolated compounds were
      as follows: ellagic acid (A), 3'-O-methyl ellagic acid (B), 3,3'-di-O-methyl
      ellagic acid (C), 3-O-methyl-3',4'-methylenedioxy ellagic acid (D). The
      inhibition constant values (Ki) for enzymatic activity, as well the IC(50) values
      found in the edematogenic and myotoxic activities, indicate that the ellagic acid
      is the best inhibitor of these activities, while compounds C and D are the
      substances with lowest capacity on inhibiting these same effects. Our results
      show that the presence of hydroxyls at position 3 or 3' (compounds A and B)
      increases the capacity of these derivatives on inhibiting these toxic effects.
      However, the presence of methoxyl groups at position 3 or 3' reduced, but did not
      completely inhibit the capacity of compounds C and D on inhibiting all the toxic
      effects studied.

PMID- 18718482
TI  - Evidence for dopamine involvement in ambulation promoted by menthone in mice.
AB  - The present study examines the mechanism that underlies the ability of menthone
      (MTN), a constituent of peppermint oil, to promote mouse ambulation. Since
      bupropion (BUP), a dopamine (DA) uptake inhibitor, promotes mouse ambulation, the
      effect of MTN combined with BUP on ambulation was investigated. The results
      showed that BUP with MTN produced an additive interaction on mouse ambulation.
      The effects of DA antagonists chlorpromazine, fluphenazine, haloperidol, SCH12679
      and spiperone on the ability of MTN to promote ambulation were then examined. All
      of these antagonists attenuated the effects of MTN. Prior exposure to the
      tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine, which inhibits
      catecholamines synthesis, decreased subsequent sensitivity to the effect of MTN.
      These results suggest that DA is involved in the ability of MTN to promote
      ambulation in mice.

PMID- 18718483
TI  - Pharmacological properties and discriminative stimulus effects of a novel and
      selective 5-HT2 receptor agonist AL-38022A [(S)-2-(8,9-dihydro-7H-pyrano[2,3
      g]indazol-1-yl)-1-methylethylamine].
AB  - AL-38022A is a novel synthetic serotonergic (5-HT) ligand that exhibited high
      affinity for each of the 5-HT2 receptor subtypes (Ki<or=2.2 nM), but a
      significantly lower (>100-fold less) affinity for other 5-HT receptors. In
      addition, AL-38022A displayed a very low affinity for a broad array of other
      receptors, neurotransmitter transport sites, ion channels, and second messenger
      elements, making it a relatively selective agent. AL-38022A potently stimulated
      functional responses via native and cloned rat (EC50 range: 1.9-22.5 nM) and
      human (EC50 range: 0.5-2.2 nM) 5-HT2 receptor subtypes including [Ca2+]i
      mobilization and tissue contractions with apparently similar potencies and
      intrinsic activities and was a full agonist at all 5-HT2 receptor subtypes. The
      CNS activity of AL-38022A was assessed by evaluating its discriminative stimulus
      effects in both a rat and a monkey drug discrimination paradigm using DOM as the
      training drug. AL-38022A fully generalized to the DOM stimulus in each of these
      studies; in monkeys MDL 100907 antagonized both DOM and AL-38022A. The
      pharmacological profile of AL-38022A suggests that it could be a useful tool in
      defining 5-HT2 receptor signaling and receptor characterization where 5-HT may
      function as a neurotransmitter.

PMID- 18718484
TI  - Who exceeds ATP-III risk thresholds? Systematic examination of the effect of
      varying age and risk factor levels in the ATP-III risk assessment tool.
AB  - OBJECTIVE: We sought to determine the levels of risk factors required to exceed
      threshold values of intermediate (> or = 10%) or high (> 20%) predicted 10-year
      risk for coronary heart disease using the Adult Treatment Panel III (ATP-III)
      Risk Assessment Tool. METHODS: Continuous risk factor values were entered into
      the risk assessment tool to examine levels of predicted 10-year risk. Both
      individual risk factors and the joint effects of varying multiple risk factors
      were systematically examined. RESULTS: Women only exceed 10% risk at ages > or =
      70 with single risk factors of HDL-cholesterol levels < 30 mg/dL or systolic
      blood pressure > 170 mm Hg. Women < or = 65 only exceed 10% risk if they are
      smokers with low HDL-cholesterol levels. In contrast, single risk factors can
      cause men over 45 to exceed 10% or 20% predicted 10-year risk. Combinations of
      only modestly elevated risk factors cause many men to exceed 10% risk at ages >
      or = 45, and to exceed 20% risk at ages > or = 55. CONCLUSIONS: Because such high
      risk factor levels are required for men < 45 years and women < 65 years to exceed
      ATP-III risk thresholds, additional means for risk communication may be needed
      for individuals with elevated risk factors in these age ranges.

PMID- 18718485
TI  - pH induced structural alterations in an aspartic protease from Vigna radiata
      indicating an alkali induced molten globule state.
AB  - pH-dependent transitions in secondary and tertiary structure are described for a
      plant aspartic protease from Vigna radiata. The enzyme was pH stable with pH
      optima of 3.0. The Lineweaver Burk analysis at various pH yielded pKa values of
      3.3 and 4.29 indicating acidic amino acids at the active site of the enzyme. The
      structural changes exemplified compact secondary structure collapsed tertiary
      structure and exposure of hydrophobic patches at pH 10. The changes at pH 10 are
      typical of a molten globule state. This alkali induced molten globule is novel
      since acid induced molten globule state is more reported.

PMID- 18718486
TI  - The sensory-discriminative and affective-motivational aspects of pain.
AB  - What is the difference between pain and standard exteroceptive perceptual
      processes, such as vision or audition? According to the most common view, pain
      constitutes the internal perception of bodily damage. Following on from this
      definition, pain is just like exteroceptive perception, with the only difference
      being that it is not oriented toward publicly available objects, but rather
      toward events that are taking place in/to one's own body. Many theorists,
      however, have stressed that pain should not be seen as a kind of perception, but
      rather that it should be seen as a kind of affection or motivation to act
      instead. Though pain undeniably has a discriminatory aspect, what makes it
      special is its affective-motivational quality of hurting. In this article, we
      discuss the relation between pain and perception, at both the conceptual and
      empirical levels. We first review the ways in which the perception of internal
      damage differs from the perception of external objects. We then turn to the
      question of how the affective-motivational dimension of pain is different from
      the affective-motivational aspects that are present for other perceptual
      processes. We discuss how these differences between pain and exteroceptive
      perception can account for the fact that the experience of pain is more
      subjective than other perceptual experiences.

PMID- 18718487
TI  - Serum amyloid A induces CCL20 secretion in mononuclear cells through MAPK (p38
      and ERK1/2) signaling pathways.
AB  - Although the serum levels of SAA had been reported to be upregulated during
      inflammatory/infectious process, the role of this acute-phase protein has not
      been completely elucidated. In previous studies, we demonstrated that SAA
      stimulated the production of TNF-alpha, IL-1beta, IL-8, NO, and ROS by
      neutrophils and/or mononuclear cells. Herein we demonstrate that SAA induces the
      expression and release of CCL20 from cultured human blood mononuclear cells. We
      also focus on the signaling pathways triggered by SAA. In THP-1 cells SAA
      promotes phosphorylation of p38 and ERK1/2. Furthermore, the addition of SB203580
      (p38 inhibitor) and PD98059 (ERK 1/2 inhibitor) inhibits the expression and
      release of CCL20 in mononuclear cells treated with SAA. Our results point to SAA
      as an important link of innate to adaptive immunity, once it might act on the
      recruitment of mononuclear cells.

PMID- 18718488
TI  - Antigen-independent generation of a unique CD4 T cell-subset with aging and its
      persistent unresponsiveness.
AB  - Aging leads to a decline in the reactivity of CD4 T cells, in humans and mice.
      However, we have reported that not all CD4 T cells in aged mice were
      hyporesponsive, that is, a particular subset maintained the ability to mount a
      normal response. In this study, we examined the possibility of recalling
      reactivity in the hyporesponsive CD4 T cell-subset in aged mice. In vivo
      experiments revealed the changes in CD4 T cell-subsets in aged mice to be antigen
      independent and aging-dependent. Once the CD4 T cells became hyporesponsive, they
      persistently exhibited a weak response. Furthermore, immunization with a co
      stimulatory antibody had no effect on T cell-responses in aged mice, although it
      had a significant effect in young mice. As this hyporesponsive subset accounts
      for the majority of CD4 T cells in aged mice, it is important to elucidate the
      cause of the hyporesponsiveness.

PMID- 18718489
TI  - Rapid molecular detection of the H275Y oseltamivir resistance gene mutation in
      circulating influenza A (H1N1) viruses.
AB  - In early 2008, drug susceptibility surveillance of influenza viruses in Europe
      revealed that some influenza A viruses (subtype H1N1) circulating during the
      winter season of 2007 and 2008 were resistant to the neuraminidase inhibitor,
      oseltamivir. This resistance arises due to a histidine to tyrosine substitution
      in the neuraminidase active site (H275Y in N1 nomenclature). Current methods to
      detect this mutation involve an end-point reverse transcription polymerase chain
      reaction followed by nucleotide sequencing. While accurate, this approach has the
      limitation of being time-consuming, labour-intensive and expensive. Herein we
      describe a one-step allelic discrimination assay which rapidly (2h) detects this
      resistance mutation. The sensitivity of the assay was as low as 10 copies per
      reaction and is capable of detecting the antiviral resistance mutation in a
      mixture of wild type H275 and mutant H275Y targets.

PMID- 18718490
TI  - Antinociception induced by epidural motor cortex stimulation in naive conscious
      rats is mediated by the opioid system.
AB  - Epidural motor cortex stimulation (MCS) has been used for treating patients with
      neuropathic pain resistant to other therapeutic approaches. Experimental evidence
      suggests that the motor cortex is also involved in the modulation of normal
      nociceptive response, but the underlying mechanisms of pain control have not been
      clarified yet. The aim of this study was to investigate the effects of epidural
      electrical MCS on the nociceptive threshold of naive rats. Electrodes were placed
      on epidural motor cortex, over the hind paw area, according to the functional
      mapping accomplished in this study. Nociceptive threshold and general activity
      were evaluated under 15-min electrical stimulating sessions. When rats were
      evaluated by the paw pressure test, MCS induced selective antinociception in the
      paw contralateral to the stimulated cortex, but no changes were noticed in the
      ipsilateral paw. When the nociceptive test was repeated 15 min after cessation of
      electrical stimulation, the nociceptive threshold returned to basal levels. On
      the other hand, no changes in the nociceptive threshold were observed in rats
      evaluated by the tail-flick test. Additionally, no behavioral or motor impairment
      were noticed in the course of stimulation session at the open-field test.
      Stimulation of posterior parietal or somatosensory cortices did not elicit any
      changes in the general activity or nociceptive response. Opioid receptors
      blockade by naloxone abolished the increase in nociceptive threshold induced by
      MCS. Data shown herein demonstrate that epidural electrical MCS elicits a
      substantial and selective antinociceptive effect, which is mediated by opioids.

PMID- 18718492
TI  - Functional architecture of the cell nucleus: towards comprehensive toponome
      reference maps of apoptosis.
AB  - We have recently described the MELC/TIS fluorescence robot technology that is
      capable of colocalizing at least a hundred different molecular cell components in
      one cell. The technology reveals new hierarchical properties of protein network
      organisation, referred to as the toponome, in which topologically confined
      protein clusters are interlocked within the structural framework of the cell. In
      this study we have applied MELC/TIS to construct a three-dimensional toponome map
      of the cell nucleus of a single human hepatocyte undergoing apoptosis. The map
      reveals six different spatially separated toponome domains in the nuclear
      interior of one apoptotic cell. In the drive to decipher the apoptosis-specific
      molecular network on the single cell level, the present toponome map is a first
      milestone towards the construction of much larger maps addressing hundreds of
      molecular cell components across the stages of apoptosis.

PMID- 18718491
TI  - Conditioned lick behavior and evoked responses using whisker twitches in head
      restrained rats.
AB  - To examine whisker barrel evoked response potentials in chronically implanted
      rats during behavioral learning with very fast response times, rats must be calm
      while immobilized with their head restrained. We quantified their behaviors
      during training with an ethogram and measured each individual animals' progress
      over the training period. Once calm under restraint, rats were conditioned to
      differentiate between a reward and control whisker twitch, then provide a lick
      response when presented with the correct stimulus, rewarded by a drop of water.
      Rats produced the correct licking response (after reward whisker twitch), and
      learned not to lick after a control whisker was twitched. By implementing a high
      density 64-channel electrocorticogram (ECoG) electrode array, we mapped the
      barrel field of the somatosensory cortex with high spatial and temporal
      resolution during conditioned lick behaviors. In agreement with previous reports,
      we observe a larger evoked response after training, probably related to
      mechanisms of cortical plasticity.

PMID- 18718493
TI  - Nuclear architecture and gene regulation.
AB  - The spatial organization of eukaryotic genomes in the cell nucleus is linked to
      their transcriptional regulation. In mammals, on which this review will focus,
      transcription-related chromatin positioning is regulated at the level of
      chromosomal sub-domains and individual genes. Most of the chromatin remains
      stably positioned during interphase. However, some loci display dynamic
      relocalizations upon transcriptional activation, which are dependent on nuclear
      actin and myosin. Transcription factors in association with chromatin modifying
      complexes seem to play a central role in regulating chromatin dynamics and
      positioning. Recent results obtained in this regard also give insight into the
      question how the different levels of transcriptional regulation are integrated
      and coordinated with other processes involved in gene expression. Corresponding
      findings will be discussed.

PMID- 18718494
TI  - Development of a microplate-based fluorescence immunoassay using quantum dot
      streptavidin conjugates for enumeration of putative marine bacteria, Alteromonas
      sp., associated with a benthic harpacticoid copepod.
AB  - Attached bacteria inhabit the surfaces of many marine animals--a process that may
      play important roles in the survival and transport through aquatic systems.
      However, efficient detection of these bacteria has been problematic, especially
      small aquatic animals such as benthic harpacticoid copepod. Quantum dots (QD)
      have recently emerged as a significant tool in immunofluorescence detection
      because of their unique properties compared to other fluorescent probes. In the
      present study, a polyclonal antibody was raised against the Gram-negative marine
      bacterium, Alteromonas sp. A microplate-based immunofluorescence bioassay using
      QD strepavidin conjugates was developed for quantifying putative Alteromonas sp.
      cells located on the surfaces of a marine harpacticoid copepod, Microarthridion
      littorale. The number of attached Alteromonas sp. was estimated to be 10(2)+/-8
      CFU using this method. The QD approach, coupled to a microplate assay can
      potentially provide an efficient and accurate method for rapidly detecting
      multiple bacteria species attached to small invertebrate animals because of their
      unique excitation and emission characteristics.

PMID- 18718495
TI  - Late steps of parvoviral infection induce changes in cell morphology.
AB  - Previously, virus-induced non-filopodial extensions have not been encountered in
      connection with viral infections. Here, we report emergence of long extensions
      protruding from Norden laboratory feline kidney (NLFK) and A72 (canine fibroma)
      cells infected with canine parvovirus for 72 h. These extensions significantly
      differ in length and number from those appearing in control cells. The most
      striking feature in the extensions is the length, reaching up to 130 microm,
      almost twice the average length of a healthy NLFK cell. In A72 cells, the
      extensions were even longer, up to 200 microm. The results presented here also
      suggest that the events leading to the growth of these extensions start earlier
      in infection and abnormal extension growth is detectable already at 24-h post
      infection (p.i.). These extensions may have a vital role in the cell-to-cell
      transmission of the virus.

PMID- 18718496
TI  - Enzymatic degradation of endomorphins.
AB  - Centrally acting plant opiates, such as morphine, are the most frequently used
      analgesics for the relief of severe pain, even though their undesired side
      effects are serious limitation to their usefulness. The search for new
      therapeutics that could replace morphine has been mainly focused on the
      development of peptide analogs or peptidomimetics with high selectivity for one
      receptor type and high bioavailability, that is good blood-brain barrier
      permeability and enzymatic stability. Drugs, in order to be effective, must be
      able to reach the target tissue and to remain metabolically stable to produce the
      desired effects. The study of naturally occurring peptides provides a rational
      and powerful approach in the design of peptide therapeutics. Endogenous opioid
      peptides, endomorphin-1 and endomorphin-2, are two potent and highly selective mu
      opioid receptor agonists, discovered only a decade ago, which display potent
      analgesic activity. However, extensive studies on the possible use of
      endomorphins as analgesics instead of morphine met with failure due to their
      instability. This review deals with the recent investigations that allowed
      determine degradation pathways of endomorphins in vitro and in vivo and propose
      modifications that will lead to more stable analogs.

PMID- 18718497
TI  - Cytomegalovirus vaccines fail to induce epithelial entry neutralizing antibodies
      comparable to natural infection.
AB  - Antibodies that neutralize cytomegalovirus (CMV) entry into fibroblasts are
      predominantly directed against epitopes within virion glycoproteins that are
      required for attachment and entry. However, the mechanism of CMV entry into
      epithelial and endothelial cells differs from fibroblast entry. Using assays that
      simultaneously measured neutralizing activities against CMV entry into
      fibroblasts and epithelial cells, we found that human immune sera and CMV
      hyperimmuneglobulins have on on average 48-fold higher neutralizing activities
      against epithelial cell entry compared to fibroblast entry, suggesting that
      natural CMV infections elicit neutralizing antibodies that are epithelial entry
      specific. This activity could not be adsorbed with recombinant gB. The Towne
      vaccine and the gB/MF59 subunit vaccine induced epithelial entry-specific
      neutralizing activities that were on on average 28-fold (Towne) or 15-fold
      (gB/MF59) lower than those observed following natural infection. These results
      suggest that CMV vaccine efficacy may be enhanced by the induction of epithelial
      entry-specific neutralizing antibodies.

PMID- 18718498
TI  - Memory impairment correlates with increased S100B serum concentrations in
      patients with chronic schizophrenia.
AB  - Astrocyte activation indicated by increased S100B is considered a potential
      pathogenic factor for schizophrenia. To investigate the relationship between
      astrocyte activation and cognitive performance, S100B serum concentration, memory
      performance, and psychopathology were assessed in 40 first-episode and 35 chronic
      schizophrenia patients upon admission and after four weeks of treatment. Chronic
      schizophrenia patients with high S100B were impaired concerning verbal memory
      performance (AVLT, Auditory Verbal Learning Test) compared to chronic and first
      episode patients with low S100B levels. The findings support the hypothesis that
      astrocyte activation might contribute to the development of cognitive dysfunction
      in schizophrenia.

PMID- 18718499
TI  - Role of lactoferrin in the tear film.
AB  - The surface of the eye provides an inert barrier against infection. Through its
      unique combination of antimicrobial action and anti-inflammatory activities
      lactoferrin (Lf) in the tear film plays an important role in the maintenance of
      ocular health. In order to maintain clarity the eye must provide immunological
      defense without immunopathology. Along with physical barriers, soluble plasma
      factors and other proteins such as lysozyme, Lf produced by the acinar cells of
      the lacrimal gland serves a number of roles in defense for this purpose. Lf in
      tears provides antimicrobial efficacy by binding free iron thus reducing the
      availability of iron necessary for microbial growth and survival as well as
      pathogenesis. Lf has been shown to inhibit biofilm formation and thus may play a
      role in protecting contact lens surfaces from colonization. Virus particles'
      entry into epithelial cells is inhibited by Lf while an excess of Lf in tear film
      is thought to limit the opportunistic Lf-mediated bridging of adenovirus and host
      cell that occurs in other tissues. Lf dampens the classical complement activation
      pathway by binding to markers of inflammation and immune activation while
      pathogen-associated molecular patterns such as lipopolysaccharide (LPS) are
      targeted by Lf for removal through tears and hydrodynamic flushing. This review
      focuses on the role of Lf in human tear film and its contribution to ocular
      health during contact lens wear.

PMID- 18718500
TI  - Topology and thermodynamics of gaseous ligands diffusion paths in human
      neuroglobin.
AB  - The physiological role of recently discovered human neuroglobin (Ngb) is still
      unknown. Sound hypothesis says that it protects brain during hypoxia. In this
      paper the advanced potential of mean force by implicit ligand sampling (PMF/ILS)
      method is used to study the free energy landscape of Ngb for O(2), NO and CO
      ligands. The multiple diffusion paths are discovered and four ligand binding
      cavities are determined. The data show that certain regions are easily accessible
      by O(2) and NO but are protected from CO. Free energy landscapes provide
      realistic data for stochastic models of ligand diffusion in proteins.

PMID- 18718501
TI  - Observation of optimal gecko's adhesion on nanorough surfaces.
AB  - In this letter we report experimental observations on the times of adhesion of
      living Tokay geckos (Gekko geckos) on polymethylmethacrylate (PMMA) inverted
      surfaces. Two different geckos (male and female) and three surfaces with
      different root mean square (RMS) roughness (RMS=42, 618 and 931 nm) have been
      considered, for a total of 72 observations. The measured data are proved to be
      statistically significant, following the Weibull Statistics with coefficients of
      correlation between 0.781 and 0.955. The unexpected result is the observation of
      a maximal gecko adhesion on the surface with intermediate roughness of RMS=618
      nm, that we note has waviness comparable to the seta size.

PMID- 18718502
TI  - The comparison of biophysical properties of DB-67 and its ester DB-67-4ABTFA
      determined by fluorescence spectroscopy methods.
AB  - Fluorescence spectroscopy methods are applied to the study of camptothecin
      analogue DB-67 and its ester DB-67-4ABTFA (trifluoroacetic acid salt of 20(S)
      aminobutyrate substituted DB-67). Camptothecin and many of its analogues exhibit
      anticancer properties. They are fluorescent compounds, so using the method of
      fluorescence anisotropy measurements and fluorescence spectra recording many
      biophysical properties can be determined including affinity to proteins and
      membranes. One can also observe the process of conversion of the ester into DB
      67. Active lactone form of camptothecin in fluids at pH 7.4 hydrolyses and
      converts into inactive carboxylate. Process of camptothecin deactivation is
      accelerated in plasma and after about 2h the total conversion to carboxylate form
      occurs. It is caused by fast and irreversible binding of carboxylate form to the
      human serum albumin (HSA). Camptothecin carboxylate bound to HSA does not
      lactonise. On the other hand, camptothecin lactone binding to membranes is
      reversible, but as long as lactone form bound to membranes does not hydrolyse.
      Knowledge of binding properties to proteins and membranes permits to select among
      many camptothecin analogues the ones exhibiting desirable behavior in
      physiological conditions: high affinity of lactone form to membranes and low
      affinity of carboxylate form to albumin. The studied DB-67 and DB-67-4ABTFA
      fulfill these requirements.

PMID- 18718503
TI  - On the spherical prototype of a complex dissipative late-stage formation seen in
      terms of least action Vojta-Natanson principle.
AB  - The spherical prototype of a crystalline and/or disorderly formation may help in
      understanding the final stages of many complex biomolecular arrangements. These
      stages are important for both naturally organized simple biosystems, such as
      protein (or, other amphiphilic) aggregates in vivo, as well as certain their
      artificial counterparts, mimicking either in vitro or in silico their structure
      property principal relationship. For our particular one-seed based realization of
      a protein crystal/aggregate late-stage nucleus grown from nearby fluctuating
      environment, it turns out that the (osmotic-type) pressure could be, due to local
      inhomogeneities, and their dynamics shown up in the double layer tightly
      surrounding the growing object, still an appreciably detectable quantity. This is
      due to the fact that a special-type generalized thermodynamic (Vojta-Natanson)
      momentum, subjected to the nucleus' surface, is manifested interchangeably,
      whereas the total energy of the solution in the double layer could not be such
      within the stationary regime explored. It is plausible since the double layer
      width, related to the object's surface, contributes ultimately, while based on
      the so-defined momentum's changes, to the pressure within this narrow flickering
      zone, while leaving the total energy fairly unchanged. From the hydrodynamic
      point of view, the system behaves quite trivially, since the circumventing flow
      should rather be of laminar, thus not-with-matter supplying, character.

PMID- 18718504
TI  - Neuronal RA175/SynCAM1 isoforms are processed by tumor necrosis factor-alpha
      converting enzyme (TACE)/ADAM17-like proteases.
AB  - RA175/SynCAM1, a member of immunoglobulin superfamily 4 (Igsf4; recently named
      Cadm1), is a cell adhesion molecule involved in the formation of a functional
      synapse. Little is known about the modulation of RA175/SynCAM1-mediated synaptic
      formation and plasticity. Neurons express two major isoforms containing exons 7
      8a-8b-9 and exons 7-8b-9. We found that these isoforms were processed within an
      11-amino acid sequence, encoded by exon 8b, near the transmembrane domain. TNF
      alpha protease inhibitor-1 (TAPI-1) blocked the processing of RA175/SynCAM1
      (exons 7-8a-8b-9). Furthermore, TAPI-1 increased the number of synaptophysin and
      RA175/SynCAM1 colocalization on the dendrites of neurons. Non-cleaved
      RA175/SynCAM1 was located at the synapse and membrane-bound, cleaved fragments
      were detected at the non-synaptic region of dendrites. These results suggest that
      tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM17-like proteases play a
      role in synaptic formation to generate specific neuronal connections by
      processing the excess amount of RA175/SynCAM1 located in the non-synaptic region.

PMID- 18718505
TI  - Blood brain barrier (BBB) dysfunction associated with increased expression of
      tissue and urokinase plasminogen activators following peripheral thermal injury.
AB  - Emerging data suggests the serine proteases, tissue plasminogen activator (tPA),
      and urokinase plasminogen activator (uPA), may play a detrimental role in
      traumatic states leading to compromise of the blood brain barrier (BBB). The
      purpose of our study was to define the role of endogenous tPA and uPA on the BBB
      following peripheral burn injuries. Adult male Sprague-Dawley rats (n=46) were
      studied in control and thermal injury groups. Rats were anesthetized and
      submerged in 100 degrees C water for 6s producing a third degree burn affecting
      60-70% of the total body surface area. BBB dysfunction was then evaluated by
      measuring the amount of Evans blue and by calculating the water content in the
      brain. Levels of tPA and uPA mRNA in the brain were determined with real-time
      polymerase chain reaction (PCR) at 3 and 7h post-injury. Results showed an
      increase in the brain water content and the presence of Evans blue in the brain
      tissue of thermally injured rats, temporally associated with an increased
      expression of endogenous tPA and uPA. Our study demonstrates that peripheral
      thermal injury does induce an increase in the permeability of the BBB. A possible
      mechanism may be an increased expression of tPA and uPA.

PMID- 18718506
TI  - Brain-derived neurotrophic factor does not improve recovery after cardiac arrest
      in rats.
AB  - Increased brain-derived neurotrophic factor (BDNF) levels and extracellular
      signal regulated kinase (ERK) signaling are associated with reduced brain injury
      after cerebral ischemia. In particular, mild hypothermia after cardiac arrest
      increases BDNF and ERK signaling. This study tested whether
      intracerebroventricular infusions (0.025 microg/h x 3 days) of BDNF also improved
      recovery of rats resuscitated from cardiac arrest and maintained at 37 degrees C.
      BDNF infusions initiated at the time of cardiac arrest did not alter survival,
      neurological recovery, or histological injury. Separate experiments confirmed
      that BDNF infusions increased tissue levels of BDNF. However, these infusions did
      not increase ERK activation in hippocampus. These data suggest that increased
      BDNF levels are not sufficient to explain the beneficial effects of mild
      hypothermia after cardiac arrest, and that exogenous BDNF administration does not
      increase extracellular ERK signaling.

PMID- 18718507
TI  - Effects of ocular dominance on the vertical vergence induced by a 2-diopter
      vertical prism during standing.
AB  - This study examined the eye movement responses to vertical disparity induced by a
      2-diopter vertical prism base down while in standing position. Vertical vergence
      movements are known to be small requiring accurate measurement with the head
      stabilized, and was done with the EyeLink 2. The 2-diopter vertical prism, base
      down, was inserted in front of either the non-dominant eye (NDE) or dominant eye
      (DE) at 40 and 200 cm. The results showed that vertical vergence was stronger and
      excessive relative to the required value (i.e. 1.14 degrees ) when the prism was
      on the NDE for both distances, but more appropriate when the prism was on the DE.
      The results suggest that sensory disparity process and vertical vergence
      responses are modulated by eye dominance.

PMID- 18718508
TI  - Effect of angiotensin-related antihypertensives on brain neurotransmitter levels
      in rats.
AB  - The extensive clinical experience of angiotensin converting enzyme inhibitors and
      angiotensin AT(1) receptor antagonists as antihypertensive agents provide
      numerous examples of anecdotal evidence of improvements in cognition and mood.
      This study aimed to determine the effect of chronic treatment with the
      angiotensin converting enzyme inhibitor, perindopril, and the angiotensin AT(1)
      receptor antagonist, candesartan, on central neurotransmitter levels in the rat.
      Perindopril (1.0mg/kg/day) or candesartan (10mg/kg/day) was administered via the
      drinking water at for 1 week, while controls received water alone. At the end of
      treatment rats were sacrificed, brains removed and discrete regions dissected and
      analysed for noradrenaline, dopamine and its major metabolites, and serotonin
      content. As shown previously we found an increase in striatal dopamine levels
      after perindopril treatment, though this did not extend to the mesolimbic system
      with neurotransmitter levels unchanged in the hippocampus, nucleus accumbens and
      frontal cortex. Conversely, candesartan administration produced no change in
      dopamine, but significant decreases in both DOPAC and HVA in the striatum. In
      addition chronic candesartan infusion produced a significant increase in the
      levels of hippocampal noradrenaline and serotonin; and frontal cortex serotonin
      content. These results demonstrate that while angiotensin converting enzyme
      inhibitors and angiotensin AT(1) receptor antagonists act as antihypertensives by
      affecting the renin-angiotensin system, they have divergent actions on brain
      neurochemistry.

PMID- 18718509
TI  - Chromosomal translocations in cancer.
AB  - Genetic alterations in DNA can lead to cancer when it is present in proto
      oncogenes, tumor suppressor genes, DNA repair genes etc. Examples of such
      alterations include deletions, inversions and chromosomal translocations. Among
      these rearrangements chromosomal translocations are considered as the primary
      cause for many cancers including lymphoma, leukemia and some solid tumors.
      Chromosomal translocations in certain cases can result either in the fusion of
      genes or in bringing genes close to enhancer or promoter elements, hence leading
      to their altered expression. Moreover, chromosomal translocations are used as
      diagnostic markers for cancer and its therapeutics. In the first part of this
      review, we summarize the well-studied chromosomal translocations in cancer.
      Although the mechanism of formation of most of these translocations is still
      unclear, in the second part we discuss the recent advances in this area of
      research.

PMID- 18718510
TI  - Expression and traffic of cellular prolyl oligopeptidase are regulated during
      cerebellar granule cell differentiation, maturation, and aging.
AB  - Prolyl oligopeptidase (POP) is an endopeptidase which cleaves short proline
      containing neuropeptides, and it is involved in memory and learning. POP also has
      an intercellular function mediated through the inositol pathway, and has been
      involved in cell death. POP has been early considered as a housekeeping enzyme,
      but the recent research indicates that POP expression is regulated across tissues
      and intracellularly. In the brain, POP is exclusively expressed in neurons and
      most abundantly in pyramidal neurons of cerebral cortex, in the CA1 field neurons
      of hippocampus and in cerebellar Purkinje's cells. Intracellularly, POP is mainly
      present in the cytoplasm and some in intracellular membranes, like rough
      endoplasmic reticulum and Golgi apparatus. In this paper, we systematically
      studied the levels of expression of POP along the life of cerebellar granule
      cells (CGC) in culture and the distribution of POP within different intracellular
      compartments. We used the tight-binding inhibitor JTP-4819 covalently coupled
      with fluorescein (FJTP) as a tool to study the changes on expression and
      localization of POP protein. Our results indicate that POP activity levels are
      regulated during the life of the neurons. POP was found mainly in cytoplasm and
      neuronal projections, but at an early developmental phase significant amounts
      were found also in nuclei. Along the life of the neurons, POP activity fluctuated
      in 7-day cycles. In young neurons, the cytosolic POP activity was low but
      increased by maturation so that the activity peak coincided with full
      differentiation. Over aging, cytoplasmic POP was concentrated around nucleus, but
      the activity decreased with time. POP was also present in vesicles across the
      neuron. No major changes were seen in the nuclear or membrane bound POP over
      aging until activity disappeared upon neuronal death. This is the first time when
      POP was found in the nuclei of human neuronal cells.

PMID- 18718512
TI  - Maxicircle (mitochondrial) genome sequence (partial) of Leishmania major: gene
      content, arrangement and composition compared with Leishmania tarentolae.
AB  - We report 8420 bp of DNA sequence data from the maxicircle (mitochondrial) genome
      of Leishmania major (MHOM/SU/73/5ASKH), a much larger portion of this genome than
      has been reported previously from any Leishmania species infecting humans. This
      region contains 10 partial and complete genes: 5 protein-encoding genes (COII,
      COIII, ND1, ND7 and Cyt b); two ribosomal RNA subunits (12S and 9S) and three
      unidentified open reading frames (MURF1, MURF4 (ATPase6) and MURF5), as in the
      lizard-infecting species L. tarentolae. The genes from L. major exhibit 85-87%
      identity with those of L. tarentolae at the nucleotide level and 71-94% identity
      at the amino acid level. Most differences between sequences from the two species
      are transversions. The gene order and arrangement within the maxicircle of L.
      major are similar to those in L. tarentolae, but base composition and codon usage
      differ between the species. Codons assigned for initiation for protein-coding
      genes available for comparison are similar in five genes in the two species. Pre
      editing was identified in some of the protein-coding genes. Short intergenic non
      coding regions are also present in L. major as they are in L. tarentolae.
      Intergenic regions between 9S rRNA and MURF5, MURF1 and ND1 genes are G+C rich
      and considered to be extensive RNA editing regions. The RNA editing process is
      likely to be conserved in similar pattern in L. major as in L. tarentolae.

PMID- 18718511
TI  - Glial reactions and degeneration of myelinated processes in spinal cord gray
      matter in chronic experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) result in
      inflammatory white matter lesions in the CNS. However, information is sparse with
      regard to the effects of autoimmune demyelinating disease on gray matter regions.
      Therefore, we studied the late effects of chronic EAE in C57BL/6 mice on the
      spinal cord gray matter using immunohistochemistry. Here, EAE induced marked
      astrocytic, microglial, and macrophage activation in the ventral horn gray
      matter, without any motoneuron loss. Activated caspase-3 was also increased in
      the ventral horn gray matter. Furthermore, activated poly (ADP-ribose) polymerase
      (PARP), another apoptotic marker, co-localized with myelin basic protein (MBP) of
      oligodendrocyte processes, but not with the oligodendroglial cell body marker,
      adenomatous polyposis coli gene clone CC1 (APC-CC1), or with neurofilament marker
      (RT-97) or synaptophysin of axonal arbors. However, there was no associated
      increase in the number of terminal deoxynucleotidyl transferase (TdT) mediated
      dUTP nick end labeling positive nuclei in the spinal cord gray matter of EAE
      mice. In addition, co-localization of MBP and the low-affinity neurotrophin
      receptor, p75, was demonstrated, further supporting the notion of apoptotic
      oligodendrocyte process degeneration in the gray matter of EAE mice.

PMID- 18718513
TI  - Nanoemulsions of an anti-oxidant synergy formulation containing gamma tocopherol
      have enhanced bioavailability and anti-inflammatory properties.
AB  - The present study investigated whether MicroFluidizer Processor-based
      nanoemulsions of an antioxidant synergy formulation (ASF), containing delta,
      alpha and gamma tocopherol influenced inflammation and bioavailability in CD-1
      mice. Croton oil was applied to all animals' right ear lobe to induce
      inflammation. Auricular thickness was measured after 2 and 6h after the various
      treatments. The animal plasma and ear lobes were collected and frozen for
      bioavailability and cytokine analyses. The ASF nanoemulsions of alpha, delta, or
      gamma tocopherol significantly reduced auricular thickness compared to control
      (57, -57, and -71%, respectively) and blank nanoemulsion (-50, -50, -67%,
      respectively). Relative to the suspensions of ASF, only the nanoemulsion of ASF
      containing gamma tocopherol significantly reduced auricular thickness (-60%),
      whereas the 40% reduction with nanoemulsions of delta tocopherol compared to
      suspension was not statistically significant. Auricular concentrations of
      cytokines TNF-alpha and IL-1 alpha were significantly reduced in mice treated
      only with ASF nanoemulsions of gamma tocopherol compared to control (-53, -46%,
      respectively) and blank nanoemulsion (-52, -46%, respectively). Auricular
      thickness was significantly associated with tissue TNF-alpha (r=0.539, p<0.001)
      and IL-1 alpha concentrations (r=0.404, p=0.01). Bioavailability for gamma and
      delta was dramatically enhanced (2.2- and 2.4-folds) with the nanoemulsion
      compared to suspensions. Only the plasma gamma tocopherol concentration was
      significantly associated with auricular thickness (r=-0.643, P=0.001). In
      conclusion, nanoemulsions of ASF containing gamma, alpha, and delta tocopherol,
      have enhanced anti-inflammatory properties and increased bioavailability, with
      gamma tocopherol, in particular compared to their suspensions.

PMID- 18718514
TI  - Evaluation of generations 2, 3 and 4 arginine modified PAMAM dendrimers for gene
      delivery.
AB  - It is a matter of concern to develop and design synthetic non-viral gene carriers
      with high transfection efficiency and low cytotoxicity in gene therapy. Recently,
      various arginine conjugated dendrimers showed better performance in transfection
      and greater viability than polyethyleneimine (PEI). In this study, we synthesized
      and investigated e-PAM-R G2, 3 and 4 which are biodegradable polyamidoamine
      (PAMAM) dendrimers modified with arginine and compared that with PAMAM-R series
      containing amide bonds for gene carriers. For plasmid DNA delivery, the
      transfection efficiency of e-PAM-R G4 was higher than G3 and G2 and similar to
      PAMAM-R G4 with favorable cell viability. Moreover, they indicated significantly
      higher suppression of TEL/AML1 protein, maybe due to rapid olidonucleotide (ODNs)
      release through biodegradability of e-PAM-R. These results suggest that
      biodegradable and non-toxic e-PAM-R may be useful carriers for the gene including
      plasmid DNA, antisense ODNs and si-RNA.

PMID- 18718515
TI  - Effect of resveratrol incorporated in liposomes on proliferation and UV-B
      protection of cells.
AB  - The possibility of improving the efficacy of resveratrol, a polyphenol with
      strong antioxidant and free-radical scavenging properties, on cell proliferation
      and photoprotection by liposomal incorporation was investigated. Oligolamellar
      vesicles of different lipid compositions, loaded with resveratrol, were prepared
      and characterized by evaluating size, zeta potential, incorporation efficiency,
      electron microscopy and stability over 60 days. The effect of free and liposomal
      resveratrol on the viability of HEK 293 cells and their photoprotection after UV
      B irradiation was assessed by the MTS method. Resveratrol decreased the cell
      viability at 100microM concentration, while at 10microM increased cell
      proliferation and also achieved the most effective photoprotection.
      Photomicrographs of the treated cells from inverted light and fluorescence
      microscopy demonstrated resveratrol effectiveness at 10microM, as well as its
      toxicity at higher concentrations, based on changes in cell shape, detachment and
      apoptotic features. Interestingly, liposomes prevented the cytotoxicity of
      resveratrol at high concentrations, even at 100microM, avoiding its immediate and
      massive intracellular distribution, and increased the ability of resveratrol to
      stimulate the proliferation of the cells and their ability to survive under
      stress conditions caused by UV-B light.

PMID- 18718516
TI  - Ontogeny of serotonin and serotonin2A receptors in rat auditory cortex.
AB  - Maturation of the mammalian cerebral cortex is, in part, dependent upon multiple
      coordinated afferent neurotransmitter systems and receptor-mediated cellular
      linkages during early postnatal development. Given that serotonin (5-HT) is one
      such system, the present study was designed to specifically evaluate 5-HT tissue
      content as well as 5-HT(2A) receptor protein levels within the developing
      auditory cortex (AC). Using high performance liquid chromatography (HPLC), 5-HT
      and the metabolite, 5-hydroxyindoleacetic acid (5-HIAA), was measured in isolated
      AC, which demonstrated a developmental dynamic, reaching young adult levels early
      during the second week of postnatal development. Radioligand binding of 5-HT(2A)
      receptors with the 5-HT(2A/2C) receptor agonist, (125)I-DOI ((+/-)-1-(2,5
      dimethoxy-4-iodophenyl)-2-aminopropane HCl; in the presence of SB206553, a
      selective 5-HT(2C) receptor antagonist, also demonstrated a developmental trend,
      whereby receptor protein levels reached young adult levels at the end of the
      first postnatal week (P8), significantly increased at P10 and at P17, and
      decreased back to levels not significantly different from P8 thereafter.
      Immunocytochemical labeling of 5-HT(2A) receptors and confocal microscopy
      revealed that 5-HT(2A) receptors are largely localized on layer II/III pyramidal
      cell bodies and apical dendrites within AC. When considered together, the results
      of the present study suggest that 5-HT, likely through 5-HT(2A) receptors, may
      play an important role in early postnatal AC development.

PMID- 18718517
TI  - Study of the anti-proliferative effects and synergy of phthalides from Angelica
      sinensis on colon cancer cells.
AB  - Angelica sinensis is a Chinese medicinal herb for treating gynecological and
      gastrointestinal disorders, and also in conjunction with cancer chemotherapy. AIM
      OF THE STUDY: In the present study, the cytotoxic and anti-proliferative effects
      of three main Angelica sinensis phthalides, namely n-butylidenephthalide (BLP),
      senkyunolide A (SKA) and z-ligustilide (LGT), and their synergy on colon cancer
      HT-29 cells were investigated. Moreover, the results obtained in both human colon
      cancer HT-29 and normal colon CCD-18Co cells were compared for the investigation
      of selectivity. MATERIALS AND METHODS: MTT and [3H] thymidine incorporation
      assays were used for the evaluation of cytotoxic and anti-proliferative effects,
      respectively. Interactions among phthalides were determined by median-effect
      analysis. RESULTS: All three phthalides dose-dependently decreased cell viability
      more potently in HT-29 than in CCD-18Co cells. The IC50 values for inhibition of
      cell proliferation for SKA, LGT and BLP were 54.17+/-5.10, 60.63+/-6.79 and
      236.90+/-18.22microM, respectively, in HT-29 cells. Angelica sinensis extract
      demonstrated significant synergy in inhibiting cell proliferation. CONCLUSIONS:
      The three phthalides might have anti-cancer potential, yet the phthalides, in
      combination with other ingredients in Angelica sinensis extract, display
      significant synergy leading to a stronger anti-tumor effect.

PMID- 18718518
TI  - Antimicrobial activity of the crude extracts and compounds from Ficus
      chlamydocarpa and Ficus cordata (Moraceae).
AB  - The aim of this study was to evaluate the antimicrobial activity of the methanol
      extracts from Ficus chlamydocarpa (FCR), Ficus cordata (FCB), mixture of the two
      plants (FCM), as well as that of the isolated flavonoids Alpinumisoflavone (2),
      Genistein (3), Laburnetin (4), Luteolin (5) (isolated from FCR), Catechin (7) and
      Epiafzelechin (8) (isolated from FCB). Mycobacteria, fungi, Gram-positive and
      Gram-negative bacterial species were tested for their susceptibility to the above
      samples. The microplate dilution and radiometric respiratory methods were used to
      determine the susceptibility testing of the samples against Mycobacterium
      smegmatis and Mycobacterium tuberculosis, respectively. The disc diffusion assay
      was used to determine the sensitivity of the samples, whilst the micro-dilution
      method was used for the determination of the minimal inhibition concentration
      (MIC) and the minimal microbicidal concentration (MMC) against fungi, Gram
      positive and Gram-negative bacterial species. All the samples except compound 7
      were found to be active to Mycobacterium smegmatis and the MIC ranged from 0.61
      to 312.50microg/ml. Compound 4 showed the best activity against Mycobacterium
      tuberculosis exhibiting an MIC of 4.88microg/ml. The results of the diffusion
      test indicated that the crude extract from FCB, FCM as well as compounds 5 and 8
      were able to prevent the growth of all tested (fungi, Gram-positive and Gram
      negative bacteria) organisms. The inhibition effect of the crude extract from
      Ficus chlamydocarpa was observed on 10 (62.5%) of the 16 tested microorganisms
      (excluding mycobacteria) whereas that of compounds 4, 2 and 3 was respectively
      noted on 14 (87.5%), 8 (50.0%) and 7 (39.9%) of the tested microbial species. FCB
      was found to be more active than FCR on most of the tested organisms. The results
      provided evidence that the studied plants extract, as well as some of the
      isolated compounds might be potential sources of new antimicrobial drug.

PMID- 18718519
TI  - Inhibition of astrocytes promotes long-distance growing nerve fibers in ventral
      mesencephalic cultures.
AB  - Tyrosine hydroxylase-positive nerve fiber formation occurs in two diverse
      morphological patterns in rat fetal ventral mesencephalic slice cultures; one is
      non-glial-associated and the other is glial-associated. The aim of this study was
      to characterize the non-glial-associated nerve fibers and its relation to
      migration of astrocytes. Organotypic slice cultures were prepared from embryonic
      days 12, 14, and 18 rat fetuses and maintained for 5, 7 or 14 days in vitro.
      Inhibition of cell proliferation using cytosine beta-D-arabinofuranoside was
      conducted in embryonic day 14 ventral mesencephalic cultures. The treatment
      impaired astrocytic migration at 7 and 14 days in vitro. The reduced migration of
      astrocytes exerted a negative effect on the glial-associated tyrosine hydroxylase
      positive nerve fibers, reducing the outgrowth from the tissue slice. The non
      glial-associated outgrowth was, however, positively affected by reduced
      astrocytic migration, reaching distances around 3mm in 2 weeks, and remained for
      longer time in culture. Co-cultures of fetal ventral mesencephalon and frontal
      cortex revealed the cortex as a target for the non-glial-associated tyrosine
      hydroxylase-positive outgrowth. The age of the fetal tissue at plating affected
      the astrocytes such that older tissue increased the length of astrocyte
      migration. Younger tissue at plating promoted the presence of non-glial
      associated outgrowth and long radial-glia-like processes, while older tissue
      promoted migration of neurons instead of formation of nerve fiber network. In
      conclusion, inhibition of astrocytic proliferation promotes the persistence of
      long-distance growing tyrosine hydroxylase-positive nerve fibers in ventral
      mesencephalic slices cultures. Furthermore, the long-distance growing nerve
      fibers target the frontal cortex and are absent in cultures derived from older
      tissue.

PMID- 18718520
TI  - Genetic subspecies diversity of the chimpanzee CD4 virus-receptor gene.
AB  - Chimpanzees are naturally and asymptomatically infected by simian
      immunodeficiency virus (SIV). Pathogenic properties of SIV/HIV vary and
      differences in susceptibility and pathogenicity of SIV/HIV depend in part on host
      specific factors such as virus-receptor/co-receptor interactions. Since CD4 plays
      a primary role in virus binding and since SIVcpz have been found only in two
      African chimpanzee subspecies, we characterized the genetic diversity of CD4
      receptors in all four recognized subspecies of chimpanzees. We found noticeable
      variation in the first variable region V1 of CD4 and in intron six among the
      subspecies of chimpanzees. We found the CD4 receptor to be conserved in
      individuals belonging to the P. t. verus subspecies and divergent from the other
      three subspecies, which harbored highly variable CD4 receptors. The CD4 receptor
      of chimpanzees differed from that of humans. We question whether the observed
      diversity can explain the species-specific differences in susceptibility to and
      pathogenicity of SIV/HIV.

PMID- 18718521
TI  - Screening reveals conserved and nonconserved transcriptional regulatory elements
      including an E3/E4 allele-dependent APOE coding region enhancer.
AB  - We performed an unbiased experimental search for enhancers and silencers in a 153
      kb region containing the human apolipoprotein (APO) E/C1/C4/C2 gene cluster using
      shotgun cloning into a luciferase vector. A continuum of transcriptional effect
      sizes was observed, possibly explaining the limited success of bioinformatics in
      identifying regulatory regions. We identified nine statistically significant
      enhancers and five silencers functional in either liver or astrocyte cells,
      including two previously known enhancers. Only two of the fourteen elements
      contained conserved noncoding sequences. Within the coding sequence of the APOE
      gene we identified an enhancer for the E4 allele associated with Alzheimer's
      disease, but not E3. The single nucleotide polymorphism (SNP) causing the E4/E3
      amino acid substitution was responsible for these variations, potentially
      explaining the higher expression levels of E4. Our results suggest a wider
      variety of mammalian transcriptional regulatory sequences than is currently
      recognized and that these may include coding region SNPs.

PMID- 18718522
TI  - Evolution of genes on the Salmonella Virulence plasmid phylogeny revealed from
      sequencing of the virulence plasmids of S. enterica serotype Dublin and
      comparative analysis.
AB  - Salmonella enterica serotype Dublin harbors an approximately 80-kb virulence
      plasmid (pSDV), which mediates systemic infection in cattle. There are two types
      of pSDV: one is pSDVu (pOU1113) in strain OU7025 and the other pSDVr (pOU1115) in
      OU7409 (SD Lane) and many clinical isolates. Sequence analysis showed that pSDVr
      was a recombinant plasmid (co-integrate) of pSDVu and a plasmid similar to a 35
      kb indigenous plasmid (pOU1114) of S. Dublin. Most of the F-transfer region in
      pSDVu was replaced by a DNA segment from the pOU1114-like plasmid containing an
      extra replicon and a pilX operon encoding for a type IV secretion system to form
      pSDVr. We reconstructed the particular evolutionary history of the seven
      virulence plasmids of Salmonella by comparative sequence analysis. The whole
      evolutionary process might begin with two different F-like plasmids (IncFI and
      IncFII), which then incorporated the spv operon and fimbriae operon from the
      chromosome to form the primitive virulence plasmids. Subsequently, these plasmids
      descended by deletion from a relatively large plasmid to smaller ones, with some
      recombination events occurring over time. Our results suggest that the phylogeny
      of virulence plasmids as a result of frequent recombination provides the
      opportunity for rapid evolution of Salmonella in response to the environmental
      cues.

PMID- 18718524
TI  - Oxidative stress in diseases of the human cornea.
AB  - Intense exposure to light, robust metabolic activity, and high oxygen tension
      render the human eye particularly vulnerable to oxidative damage and the list of
      ophthalmological disorders implicating reactive oxygen and nitrogen species is
      rapidly expanding. Here, we review the roles of oxidative stress in the
      etiopathogeneses and pathophysiology of diseases of the human cornea including
      pterygium, keratoconus, trauma and chemical injury, and a host of inflammatory,
      metabolic, degenerative, and iatrogenic conditions. Data from animal and tissue
      culture experimentation germane to these conditions are also adduced.

PMID- 18718523
TI  - Decreasing peroxiredoxin II expression decreases glutathione, alters cell cycle
      distribution, and sensitizes glioma cells to ionizing radiation and H(2)O(2).
AB  - Glioblastomas are notorious for their resistance to ionizing radiation and
      chemotherapy. We hypothesize that this resistance to ionizing radiation is due,
      in part, to alterations in antioxidant enzymes. Here, we show that rat and human
      glioma cells overexpress the antioxidant enzyme peroxiredoxin II (Prx II). Glioma
      cells in which Prx II is decreased using shRNA exhibit increased hyperoxidation
      of the remaining cellular Prxs, suggesting that the redox environment is more
      oxidizing. Of interest, decreasing Prx II does not alter other antioxidant
      enzymes (i.e., catalase, GPx, Prx I, Prx III, CuZnSOD, and MnSOD). Analysis of
      the redox environment revealed that decreasing Prx II increased intracellular
      reactive oxygen species in 36B10 cells; extracellular levels of H(2)O(2) were
      also increased in both C6 and 36B10 cells. Treatment with H(2)O(2) led to a
      further elevation in intracellular reactive oxygen species in cells where Prx II
      was decreased. Decreasing Prx II expression in glioma cells also reduced
      clonogenic cell survival following exposure to ionizing radiation and H(2)O(2).
      Furthermore, lowering Prx II expression decreased intracellular glutathione and
      resulted in a significant decline in glutathione reductase activity, suggesting a
      possible mechanism for the observed increased sensitivity to oxidative insults.
      Additionally, decreasing Prx II expression increased cell cycle doubling times,
      with fewer cells distributed to S phase in C6 glioma cells and more cells
      redistributed to the most radiosensitive phase of the cell cycle, G2/M, in 36B10
      glioma cells. These findings support the hypothesis that inhibiting Prx II
      sensitizes glioma cells to oxidative stress, presenting Prxs as potential
      therapeutic targets.

PMID- 18718525
TI  - Telomerase deficiency promotes oxidative stress by reducing catalase activity.
AB  - Telomere shortening and redox imbalance have been related to the aging process.
      We used cultured mouse embryonic fibroblasts (MEF) isolated from mice lacking
      telomerase activity (Terc(-/-)) to analyze the redox balance and the functional
      consequences promoted by telomerase deficiency. Comparison with wild-type (WT)
      MEF showed that Terc(-/-) MEF had greater oxidant damage, showing higher
      superoxide anion and hydrogen peroxide production and lower catalase activity.
      Restoration of telomerase activity in Terc(-/-) MEF increased catalase expression
      and activity. TGF-beta1 and collagen type IV levels were higher in Terc(-/-) than
      in WT MEF. TGF-beta1 promoter activity decreased when Terc(-/-) MEF were
      incubated with exogenous catalase, suggesting that catalase deficiency is the
      cause of the TGF-beta1 increase. Similar results were obtained in vivo.
      Homogenized renal cortex from 6-month-old Terc(-/-) showed higher oxidant
      capacity, lower catalase activity, greater oxidative damage, and higher TGF-beta1
      and fibronectin levels than that from WT mice. In summary, telomerase deficiency
      reduces catalase activity, determining a redox imbalance that promotes
      overexpression of TGF-beta1 and extracellular matrix proteins.

PMID- 18718526
TI  - Commonalities of genetic resistance to spontaneous autoimmune and free radical-
      mediated diabetes.
AB  - ALR/Lt, a NOD-related mouse strain, was selected for resistance to alloxan free
      radical-mediated diabetes (ALD). Despite extensive genomic identity with NOD
      (>70%), ALR mice display strong resistance to autoimmune type 1 diabetes (T1D)
      due to both an unusual elevation in systemic antioxidant defenses and a reduction
      in cellular ROS production that extends to the beta cell level. Reciprocal
      backcross to NOD previously linked the ALR-derived T1D resistance to Chr. 3, 8,
      and 17 as well as to the ALR mt-Nd2(a) allele encoded by the mitochondrial genome
      (mtDNA). To determine whether any of the ALR-derived loci protecting against T1D
      also protected against ALD, 296 six-week-old F2 mice from reciprocal outcrosses
      were alloxan-treated and assessed for diabetes onset, and a genome-wide scan
      (GWS) was conducted. GWS linked mt-Nd2 as well as three nuclear loci with alloxan
      induced diabetes. A dominant ALR-derived ALD resistance locus on Chr. 8
      colocalized with the ALR-derived T1D resistance locus identified in the previous
      backcross analysis. In contrast, whereas ALR contributed a novel T1D resistance
      locus on Chr. 3 marked by Susp, a more proximal ALR-derived region marked by Il-2
      contributed ALD susceptibility, not resistance. In addition, a locus was mapped
      on Chr. 2, where heterozygosity provided heightened susceptibility. Tests for
      alloxan sensitivity in ALR conplastic mice encoding the NOD mt-Nd2(c) allele and
      NOD mice congenic for the protective Chr. 8 locus supported our mapping results.
      Alloxan sensitivity was increased in ALR.mt(NOD) mice, whereas it was decreased
      by congenic introduction of ALR genome on Chr. 8 into NOD. These data demonstrate
      both similarities and differences in the genetic control of T1D versus ROS
      induced diabetes.

PMID- 18718527
TI  - Bz-423 superoxide signals apoptosis via selective activation of JNK, Bak, and
      Bax.
AB  - Bz-423 is a proapoptotic 1,4-benzodiazepine with potent therapeutic properties in
      murine models of lupus and psoriasis. Bz-423 modulates the F(1)F(0)-ATPase,
      inducing the formation of superoxide within the mitochondrial respiratory chain,
      which then functions as a second messenger initiating apoptosis. Herein, we
      report the signaling pathway activated by Bz-423 in mouse embryonic fibroblasts
      containing knockouts of key apoptotic proteins. Bz-423-induced superoxide
      activates cytosolic ASK1 and its release from thioredoxin. A mitogen-activated
      protein kinase cascade follows, leading to the specific phosphorylation of JNK.
      JNK signals activation of Bax and Bak which then induces mitochondrial outer
      membrane permeabilization to cause the release of cytochrome c and a commitment
      to apoptosis. The response of these cells to Bz-423 is critically dependent on
      both superoxide and JNK activation as antioxidants and the JNK inhibitor SP600125
      prevents Bax translocation, cytochrome c release, and cell death. These results
      demonstrate that superoxide generated from the mitochondrial respiratory chain as
      a consequence of a respiratory transition can signal a sequential and specific
      apoptotic response. Collectively, these data suggest that the selectivity of Bz
      423 observed in vivo results from cell-type specific differences in redox balance
      and signaling by ASK1 and Bcl-2 proteins.

PMID- 18718528
TI  - Serine 396 of PDK1 is required for maximal PKB activation.
AB  - Protein kinase B (PKB; also known as Akt) is important for mediating survival and
      proliferation signals. Following activation, PKB shuttles to various compartments
      of the cell, including the nucleus, where it phosphorylates an array of targets.
      PKB is phosphorylated at T308 by its activator PDK1. PDK1 is normally excluded
      from the nucleus via a nuclear exclusion sequence (NES), and our previous work
      suggested that nuclear exclusion can be attenuated by IGF-1-induced
      phosphorylation of S396 proximal to the NES. No studies have been done to test
      the significance of S396 phosphorylation or the impact of nuclear accumulation of
      PDK1 on PKB activation. To address these questions, we created isogenic embryonic
      stem cell (ESC) lines expressing various alleles of PDK1 within a PDK1-/-
      background. Disruption of the NES domain of PDK1 correlated with elevated PKB
      phosphorylation at both T308 and S473. In contrast, mutation of S396 to alanine
      reduced PDK1 nuclear localization and reduced PKB phosphorylation and activation.
      The loss of phosphorylation of PKB by S396A mutation was rescued by forcing
      nuclear PDK1 or by conversion of S396 to an aspartic acid. The phosphorylation of
      the PKB substrate FOXO3alpha was reduced in S396A PDK1 ESC. Other known and
      suspected PKB substrates, including GSK3 and Raf1, were unaffected. This study
      therefore reveals that S396 plays a role in the activation of PKB leading to the
      regulated phosphorylation of some PKB substrates including FOXO3alpha.

PMID- 18718530
TI  - A critical evaluation of current staging of alpha-synuclein pathology in Lewy
      body disorders.
AB  - The two most frequent synucleinopathies, Parkinson disease (PD) or brainstem
      predominant type of Lewy body disease, and dementia with Lewy bodies (DLB), are
      neurodegenerative multisystem disorders with widespread occurrence of alpha
      synuclein containing deposits in the central, peripheral, and autonomic systems.
      For both Lewy body-related disorders staging/classification systems based on
      semiquantitative assessment of the distribution and progression pattern of alpha
      synuclein pathology are used that are considered to be linked to clinical
      dysfunctions. In PD a six-stage system is suggested to indicate a predictable
      sequence of lesions with ascending progression from medullary and olfactory
      nuclei to the cortex, the first two presymptomatic stages related to incidental
      Lewy body disease, stages 3 and 4 presenting with motor symptoms and the last two
      (cortical) stages frequently associated with cognitive impairment. DLB, according
      to consensus pathologic guidelines, by semiquantitative scoring of alpha
      synuclein pathology (Lewy body density and distribution) in specific brain
      regions, is distinguished into three phenotypes (brainstem, transitory/limbic and
      diffuse cortical), also considering concomitant Alzheimer-related pathology.
      Recent retrospective clinico-pathologic studies, although largely confirming the
      staging system, particularly for younger onset PD with long duration, have shown
      that between 6.3 and 43% of cases did not follow the proposed caudo-rostral
      progression pattern of alpha-synuclein pathology. In 7 to 8.3% of clinically
      manifested PD cases with synuclein inclusions in midbrain and cortex
      corresponding to LB stages 4-5 the medullary nuclei were spared, whereas mild
      parkinsonian symptoms were already observed in stages 2 and 3. There is
      considerable clinical and pathologic overlap between PD (with or without
      dementia) and DLB, corresponding to Braak LB stages 5 and 6, both frequently
      associated with variable Alzheimer-type pathology. Dementia often does not
      correlate with progressed stages of Lewy body pathology, but is related to
      concomitant Alzheimer lesions or mixed pathologies. There is no relationship
      between Braak LB stages and clinical severity of PD. Therefore, the predictive
      validity of this concept is doubtful, since in large unselected autopsy series 30
      to 55% of elderly subjects with widespread alpha-synuclein pathology (Braak
      stages 5-6) revealed no definite neuropsychiatric symptoms or were not
      classifiable, indicating compensatory mechanisms of the brain. The causes and
      molecular basis of rather frequent deviations from the proposed caudo-rostral
      progression of alpha-synuclein pathology in PD, its relation to the onset of
      classical parkinsonian symptoms, the causes for the lack of definite clinical
      symptoms despite widespread alpha-synuclein pathology in the nervous system,
      their relations to Alzheimer-type lesions, and the pathophysiologic impact of
      both pathologies remain to be further elucidated.

PMID- 18718531
TI  - c-Jun NH(2)-terminal kinase mediates leptin-stimulated androgen-independent
      prostate cancer cell proliferation via signal transducer and activator of
      transcription 3 and Akt.
AB  - Obesity is associated with advanced prostate cancer. Here we demonstrate that in
      mouse prostate cancer TRAMP-C1 cells epididymal fat extracts from high-fat diet
      fed obese mice stimulate androgen-independent cell growth more significantly than
      those from low-fat diet-fed lean mice or genetically obese leptin-deficient ob/ob
      mice in correlation with leptin concentrations. This result suggests that obesity
      promotes androgen-independent prostate cancer cell growth via adipose leptin. We
      have reported that added leptin stimulates androgen-independent prostate cancer
      cell proliferation through c-Jun NH(2)-terminal kinase (JNK). As with JNK, signal
      transducer and activator of transcription 3 (STAT3) and Akt are implicated in
      androgen-independent prostate cancer. In this study, we identify novel
      interaction of these three molecules in leptin-stimulated androgen-independent
      cell proliferation. Leptin activates JNK, STAT3 and Akt in a biphasic manner with
      a similar time-course. Pharmacological JNK inhibition suppresses leptin
      stimulated DNA binding activity, as well as Ser-727 phosphorylation, of STAT3.
      Since JNK upregulates STAT3 activity via Ser-727 phosphorylation, JNK mediates
      leptin-stimulated STAT3 activation through Ser-727 phosphorylation. Moreover, JNK
      inhibition impairs leptin-stimulated Ser-473 phosphorylation of Akt that is
      required for its activation. Thus, JNK is involved in leptin-stimulated Akt
      activation. These findings together indicate that JNK mediates leptin-stimulated
      androgen-independent prostate cancer cell proliferation via STAT3 and Akt.

PMID- 18718529
TI  - Catabolite repression control of flagellum production by Serratia marcescens.
AB  - Serratia marcescens is an emerging opportunistic pathogen with a remarkably broad
      host range. The cAMP-regulated catabolite repression system of S. marcescens has
      recently been identified and demonstrated to regulate biofilm formation through
      the production of surface adhesions. Here we report that mutations in components
      of the catabolite repression system (cyaA and crp) eliminate flagellum production
      and swimming motility. Exogenous cAMP was able to restore flagellum production to
      adenylate cyclase mutants, as determined by transmission electron microscopy and
      PAGE analysis. A transposon-generated suppressor mutation of the crp motility
      defect mapped to upstream of the flhDC operon. This suppressor mutation resulted
      in an upregulation of flhD expression and flagellum production, indicating that
      flhDC expression is sufficient to restore flagellum production to crp mutants.
      Lastly, and contrary to a previous report, we found that flhD expression is
      controlled by the catabolite repression system using quantitative RT-PCR.
      Together, these data indicate that flagellum production is regulated by the cAMP
      dependent catabolite repression system. Given the role of flagella in bacterial
      pathogenicity, the regulatory pathway described here may assist us in better
      understanding the putative role of motility in dissemination and virulence of
      this opportunistic pathogen.

PMID- 18718532
TI  - A role for the chaperone Hsp70 in the regulation of border cell migration in the
      Drosophila ovary.
AB  - Unravelling the molecular mechanisms that govern cell migration is of great
      importance towards understanding both normal embryogenesis and physiological and
      pathological processes occurring in the adult. Migration of border cells (BCs)
      during Drosophila oogenesis provides a simple and attractive model in which to
      address this problem. Here, we show that the molecular chaperone Hsp70 is
      required for BC migration. Thus, BCs lacking all Hsp70 genes present in the fly
      genome fail to reorganize their actin cytoskeleton, resulting in migration
      defects. Similar defects are found when the Hsp70 co-chaperone DnaJ-1, the
      Drosophila homolog of the human Hsp40, is overexpressed specifically in BCs. In
      addition, we provide biochemical and genetic evidence for an interaction between
      DnaJ-1 and PDGF/VEGF receptor (PVR), which is also required for actin-mediated BC
      migration. Furthermore, our results showing that PVR also interacts genetically
      with Hsp70 suggest that a mechanism by which the DnaJ-1/Hsp70 chaperone complex
      regulates BC migration is by modulating PVR function.

PMID- 18718534
TI  - Metabolic engineering in the 21st century: meeting global challenges of
      sustainability and health.

PMID- 18718535
TI  - Chitin synthases are required for survival, fecundity and egg hatch in the red
      flour beetle, Tribolium castaneum.
AB  - The synthesis of chitin, the beta-1,4-linked polymer of N-acetylglucosamine, is
      catalyzed by chitin synthase (CHS). Chitin is essential for the structural
      integrity of the exoskeletal cuticle and midgut peritrophic membrane (PM) of
      insects. To study the functions of the two chitin synthase genes, TcCHS-A and
      TcCHS-B, during embryonic and adult development in the red flour beetle,
      Tribolium castaneum, RNA interference (RNAi) experiments were carried out. When
      dsRNA for TcCHS-A was injected into male or female pharate adults, all insects
      died 5-7 d after the adult molt, and the females failed to oviposit prior to
      death. When dsTcCHS-A was injected into young adults 1-2 d post-eclosion, a
      similar lethal phenotype was obtained after 5 d and no oviposition occurred. When
      dsTcCHS-A injections were delayed until after adult maturation (7-10 d post
      eclosion), the treated females did oviposit and the resulting embryos appeared to
      develop normally. However, the chitin content of the eggs was dramatically
      reduced, the embryos became twisted and enlarged, and the eggs did not hatch.
      Adults treated with dsRNA for TcCHS-B exhibited little or no chitin in their PM
      and died about 2 wk after injection. None of the TcCHS-B-treated females
      oviposited, which was probably a secondary effect caused by starvation. These
      results extend our previous findings that CHS genes are required for all types of
      molt. The present study also demonstrates that these genes have additional roles
      in embryonic and adult development.

PMID- 18718536
TI  - Identification and characterization of the catalytic subunit of
      phosphatidylinositol 3-kinase in the yellow fever mosquito Aedes aegypti.
AB  - We characterized the catalytic subunit of phosphatidylinositol 3-kinase in Aedes
      aegypti (Aaegp110). Aaegp110 is an essential component of the insulin/ insulin
      growth factor I signaling (IIS) cascade, which regulates aging, reproduction, and
      other physiological processes in diverse organisms. The Aaegp110 gene encodes
      five putative domains (adapter binding, ras binding, C2, helical, and PI3-kinase)
      identified by sequence homology with other p110 proteins. Aaegp110 transcript was
      expressed during all A. aegypti life stages except late pupae, with particularly
      high levels in embryos. In female tissues, Aaegp110 transcript and protein were
      strongly expressed in ovaries, and moderately expressed in midguts, fat bodies
      and heads. The importance of IIS in mosquito reproduction led us to examine
      Aaegp110 ovarian expression during reproduction. Aaegp110 was expressed in
      ovaries prior to and during the first 24h post-bloodmeal, but undetectable 36-48
      h post-bloodmeal. Following oviposition Aaegp110 protein levels returned to pre
      bloodmeal levels. In reproductively arrested ovaries, Aaegp110 was present
      predominantly in the cytoplasm of follicle cells surrounding the oocyte. In vitro
      stimulation of the ovaries with 17 microM bovine insulin resulted in
      translocation of Aaegp110 from the cytoplasm to cell membrane in 15s. Lower
      concentrations (0.17 microM) also recruited Aaegp110 to the cell membrane.

PMID- 18718533
TI  - Chicken protocadherin-1 functions to localize neural crest cells to the dorsal
      root ganglia during PNS formation.
AB  - In vertebrate embryos, neural crest cells emerge from the dorsal neural tube and
      migrate along well defined pathways to form a wide diversity of tissues,
      including the majority of the peripheral nervous system (PNS). Members of the
      cadherin family of cell adhesion molecules play key roles during the initiation
      of migration, mediating the delamination of cells from the neural tube. However,
      a role for cadherins in the sorting and re-aggregation of the neural crest to
      form the PNS has not been established. We report the requirement for a
      protocadherin, chicken protocadherin-1 (Pcdh1), in neural crest cell sorting
      during the formation of the dorsal root ganglia (DRG). In embryos, cPcdh1 is
      highly expressed in the developing DRG, where it co-localizes with the
      undifferentiated and mitotically active cells along the perimeter. Pcdh1 can
      promote cell adhesion in vivo and disrupting Pcdh1 function in embryos results in
      fewer neural crest cells localizing to the DRG, with a concomitant increase in
      cells that migrate to the sympathetic ganglia. Furthermore, those cells that
      still localize to the DRG, when Pcdh1 is inhibited, are no longer found at the
      perimeter, but are instead dispersed throughout the DRG and are now more likely
      to differentiate along the sensory neuron pathway. These results demonstrate that
      Pcdh1-mediated cell adhesion plays an important role as neural crest cells
      coalesce to form the DRG, where it serves to sort cells to the mitotically active
      perimeter.

PMID- 18718537
TI  - Memory, mood, dopamine, and serotonin in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-lesioned mouse model of basal ganglia injury.
AB  - The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse serves as
      a model of basal ganglia injury and Parkinson's disease. The present study
      investigated the effects of MPTP-induced lesioning on associative memory,
      conditioned fear, and affective behavior. Male C57BL/6 mice were administered
      saline or MPTP and separate groups were evaluated at either 7 or 30 days post
      lesioning. In the social transmission of food preference test, mice showed a
      significant decrease in preference for familiar food 30 days post-MPTP compared
      to controls. Mice at both 7 and 30 days post-MPTP lesioning had increased fear
      extinction compared to controls. High Performance Liquid Chromatography analysis
      of tissues homogenates showed dopamine and serotonin were depleted in the
      striatum, frontal cortex, and amygdala. No changes in anxiety or depression were
      detected by the tail suspension, sucrose preference, light-dark preference, or
      hole-board tests. In conclusion, acute MPTP lesioning regimen in mice causes
      impairments in associative memory and conditioned fear, no mood changes, and
      depletion of dopamine and serotonin throughout the brain.

PMID- 18718538
TI  - Myocyte enhancer factor 2 mediates acetylcholine-induced expression of
      acetylcholinesterase-associated collagen ColQ in cultured myotubes.
AB  - The collagenous protein (ColQ) characterizes the collagen-tailed forms of
      acetylcholinesterase (AChE) in vertebrate muscles. Two ColQ transcripts, ColQ-1
      and ColQ-1a, driven by two distinct promoters are expressed differentially in
      mammalian slow- and fast-twitch muscles, respectively. Such expression patterns
      are determined by the contractile activity in different muscle fiber types. To
      reveal the regulatory role of muscular activity on ColQ expression, acetylcholine
      and nicotine were applied onto C2C12 muscle cells: the challenge increased the
      expression of ColQ-1/ColQ-1a mRNAs. The agonist challenge induced the
      phosphorylation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). In
      parallel, over expression of an active mutant of CaMKII enhanced both ColQ-1/ColQ
      1a mRNA levels in cultured C2C12 myotubes. Moreover, the over expression of
      myocyte enhancer factor 2 (MEF2), a downstream mediator of CaMKII, in the
      myotubes potentiated the CaMKII-induced ColQ expression. The current results
      reveal a signaling cascade that drives the expression profiles of ColQ in
      responding to activity challenge in cultured myotubes.

PMID- 18718539
TI  - High-yield expression in E. coli and refolding of the bZIP domain of activating
      transcription factor 5.
AB  - Activating transcription factor 5 (ATF5) recently has been demonstrated to play a
      critical role in promoting the survival of human glioblastoma cells. Interference
      with the function of ATF5 in an in vivo rat model caused glioma cell death in
      primary tumors but did not affect the status of normal cells surrounding the
      tumor, suggesting ATF5 may prove an ideal target for anti-cancer therapy. In
      order to examine ATF5 as a pharmaceutical target, the protein must be produced
      and purified to sufficient quantity to begin analyses. Here, a procedure for
      expressing and refolding the bZIP domain of ATF5 in sufficient yield and final
      concentration to permit assay development and structural characterization of this
      target using solution NMR is reported. Two-dimensional NMR and circular dichroism
      analyses indicate the protein exists in the partially alpha-helical, monomeric x
      form conformation with only a small fraction of ATF5 participating in formation
      of higher-order structure, presumably coiled-coil homodimerization. Despite the
      persistence of monomers in solution even at high concentration, an
      electrophoretic mobility shift assay showed that ATF5 is able to bind to the cAMP
      response element (CRE) DNA motif. Polyacrylamide gel electrophoresis and mass
      spectrometry were used to confirm that ATF5 can participate in homodimer
      formation and that this dimerization is mediated by disulfide bond formation.

PMID- 18718540
TI  - Quantifying development: Investigating highly myelinated voxels in preadolescent
      corpus callosum.
AB  - Multi-echo T(2) relaxation decay data was acquired for 5 preadolescent males (age
      range 9-12 years). A signal to noise filter appropriate for multi-exponential
      T(2) analysis was then applied to remove voxels which did not accurately fit the
      modelled curve. The remaining voxels were designated "highly myelinated" if their
      myelin water fraction (MWF) was greater than a critical value. We investigated a
      range of signal to noise filter cut-off values and highly myelinated critical
      values and demonstrated a significant correlation (r=0.990, p<0.001) between
      verbal intelligence quotient scores on the Wechsler Intelligence Scale for
      Children - Revised and myelination of the corpus callosum in children. This
      relationship is supported by a growing number of studies showing a correlation
      between white matter development and cognitive ability.

PMID- 18718541
TI  - Artefactual subcortical hyperperfusion in PET studies normalized to global mean:
      lessons from Parkinson's disease.
AB  - AIM: Recent studies of Parkinson's disease (PD) report subcortical increases of
      cerebral blood flow (CBF) or cerebral metabolic rate of glucose (CMRglc), after
      conventional normalization to the global mean. However, if the global mean CBF or
      CMRglc is decreased in the PD group, this normalization necessarily generates
      artificial relative increases in regions unaffected by the disease. This
      potential bias may explain the reported subcortical increases in PD. To test this
      hypothesis, we performed simulations with manipulation and subsequently analysis
      of sets of quantitative CBF maps by voxel-based statistics. MATERIALS AND
      METHODS: CBF images from 49 healthy volunteers were randomly assigned to four
      sets of two groups of 20 subjects. For each set, CBF images in one group were
      manipulated, while the other group served as controls. In the first simulation,
      an isolated cortical decrease was simulated. In the second simulation, focal
      increases in the globus pallidus and thalamus motor nuclei were simulated in
      addition to cortical decreases, thus emulating the putative metabolic pattern in
      PD. The data were analyzed with both the SSM method and a univariate statistical
      approach with normalization to either the global mean or to the white matter
      mean. RESULTS: In Simulation I, global normalization robustly created artefactual
      subcortical increases, irrespective of analysis methodology. Simulation II
      demonstrated that an increased signal from the small subcortical structures
      involved in PD can probably not be detected with present instrumentation and
      typically-used sample sizes. CONCLUSION: Imposing focal decreases on cortical CBF
      in conjunction with global mean normalization gives rise to spurious relative CBF
      increases in all of the regions reported to be hyperactive in PD. Since no PET
      study has reported absolute increases of CBF or CMRglc in any subcortical region
      in PD, we conclude that the relative increases reported in some studies most
      likely arise from biased normalization to the global mean.

PMID- 18718542
TI  - Role of the prefrontal cortex in human balance control.
AB  - Although recent studies have demonstrated cortical involvement in human balance
      control, there is insufficient information regarding the regions of the cerebral
      cortex that contribute to human balance control and their mechanism of action.
      Using a functional near-infrared spectroscopic system, we investigated
      perturbation-related cortical activation. External perturbations were provided
      with and without the preceding auditory warning signals 2 s before the
      perturbation. Statistical analysis by applying the general linear model showed
      significant activation in the prefrontal cortex, including the dorsolateral
      prefrontal cortex and frontal eye field after external perturbation, regardless
      of the preceding auditory warning signals. A time-line analysis revealed similar
      temporal profiles for prefrontal activation in 2 different conditions. Based on
      the contrast between the 2 conditions, we detected enhanced activation in the
      right posterior parietal cortex and supplementary motor area in the condition
      where the auditory warning signals were provided. We presumed that prefrontal
      involvement may be relevant to adequate allocation of visuospatial attention. Our
      results may facilitate the understanding of cortical mechanisms for balance
      control in humans and the underlying pathophysiology of falls.

PMID- 18718543
TI  - Crinkling and crumpling: an auditory fMRI study of material properties.
AB  - Knowledge of an object's material composition (i.e., what it is made of) alters
      how we interact with that object. Seeing the bright glint or hearing the metallic
      crinkle of a foil plate for example, confers information about that object before
      we have even touched it. Recent research indicates that the medial aspect of the
      ventral visual pathway is sensitive to the surface properties of objects. In the
      present functional magnetic resonance imaging (fMRI) study, we investigated
      whether the ventral pathway is also sensitive to material properties derived from
      sound alone. Relative to scrambled material sounds and non-verbal human
      vocalizations, audio recordings of materials being manipulated (i.e., crumpled)
      in someone's hands elicited greater BOLD activity in the right parahippocampal
      cortex of neurologically intact listeners, as well as a cortically blind
      participant. Additional left inferior parietal lobe activity was also observed in
      the neurologically intact group. Taken together, these results support a ventro
      medial pathway that is specialized for processing the material properties of
      objects, and suggest that there are sub-regions within this pathway that subserve
      the processing of acoustically-derived information about material composition.

PMID- 18718544
TI  - Real-time detection of event-related brain activity.
AB  - The complexity and inter-individual variation of brain signals impedes real-time
      detection of events in raw signals. To convert these complex signals into results
      that can be readily understood, current approaches usually apply statistical
      methods to data from known conditions after all data have been collected. The
      capability to provide meaningful visualization of complex brain signals without
      the requirement to initially collect data from all conditions would provide a new
      tool, essentially a new imaging technique, that would open up new avenues for the
      study of brain function. Here we show that a new analysis approach, called
      SIGFRIED, can overcome this serious limitation of current methods. SIGFRIED can
      visualize brain signal changes without requiring prior data collection from all
      conditions. This capacity is particularly well suited to applications in which
      comprehensive prior data collection is impossible or impractical, such as
      intraoperative localization of cortical function or detection of epileptic
      seizures.

PMID- 18718545
TI  - Genomic imprinting: a balance between antagonistic roles of parental chromosomes.
AB  - Maternally and paternally derived chromosomes might be expected to contribute
      equally to the various cellular and developmental processes in placental mammals
      and flowering plants. However, this is not true even in the case of the self
      pollinated plant, Arabidopsis, which has identical DNA sequences in both parental
      genomes. The reason for this is that some genes, called "imprinted genes", are
      expressed exclusively from paternally or maternally inherited chromosomes. As a
      result, parental chromosomes express a distinct set of genes and play different
      roles in biological processes. Here, we review and compare roles of genomic
      imprinting in flowering plants and placental mammals.

PMID- 18718546
TI  - Bone remodeling: Multiple cellular interactions required for coupling of bone
      formation and resorption.
AB  - The dynamic nature of the skeleton is achieved by a process called "remodeling"
      which involves the co-ordinated actions of osteoclasts, osteoblasts, osteocytes
      within the bone matrix and osteoblast-derived lining cells that cover the surface
      of bone. Remodeling commences with signals that initiate osteoclast formation
      followed by osteoclast-mediated bone resorption, a reversal period, and then a
      long period of bone matrix formation mediated by osteoblasts, followed by
      mineralisation of the matrix. This review will discuss each of these steps with
      particular emphasis on the communication pathways between each cell type involved
      and the roles of ephrins, sclerostin, RANKL and PTHrP.

PMID- 18718547
TI  - Keeping plants in shape: polycomb-group genes and histone methylation.
AB  - The Polycomb-group proteins (Pc-G) are transcriptional repressors that control
      many key developmental transitions in plants. Recent whole genome profiling of
      the histone methylation marks that are characteristic of the Pc-G have suggested
      many novel targets of Pc-G regulation. However, the number and nature of targets
      also suggests that Pc-G regulation may be much more dynamic than hitherto
      assumed. We discuss the role of histone methylation in gene regulation, the
      complexes involved in setting and reading the mark and how activity states may be
      reset during development.

PMID- 18718548
TI  - Model reduction and a priori kinetic parameter identifiability analysis using
      metabolome time series for metabolic reaction networks with linlog kinetics.
AB  - In this work, we present a time-scale analysis based model reduction and
      parameter identifiability analysis method for metabolic reaction networks. The
      method uses the information obtained from short term chemostat perturbation
      experiments. We approximate the time constant of each metabolite pool by their
      turn-over time and classify the pools accordingly into two groups: fast and slow
      pools. We performed a priori model reduction, neglecting the dynamic term of the
      fast pools. By making use of the linlog approximative kinetics, we obtained a
      general explicit solution for the fast pools in terms of the slow pools by
      elaborating the degenerate algebraic system resulting from model reduction. The
      obtained relations yielded also analytical relations between a subset of kinetic
      parameters. These relations also allow to realize an analytical model reduction
      using lumped reaction kinetics. After solving these theoretical identifiability
      problems and performing model reduction, we carried out a Monte Carlo approach to
      study the practical identifiability problems. We illustrated the methodology on
      model reduction and theoretical/practical identifiability analysis on an example
      system representing the glycolysis in Saccharomyces cerevisiae cells.

PMID- 18718549
TI  - Systematic genome-wide scanning for genes involved in ATP generation in
      Escherichia coli.
AB  - Adenosine 5'-triphosphate (ATP) generation is an essential biological reaction
      for all living cells. Recently, we developed a Permeable Cell Assay for high
      throughput measurement of cellular ATP synthetic activity, mainly resulting from
      glycolysis [Hara, K.Y., Mori, H., 2006. An efficient method for quantitative
      determination of cellular ATP synthetic activity. J. Biomol. Screen. 11, 310
      317]. By using this method, we determined the cellular ATP synthetic activity in
      the stationary phase of a complete set of single-gene deletion strains of
      Escherichia coli. Their activities ranged from a minimum of 2% to a maximum of
      445%, relative to parental strains. Deletions of metabolism-related genes
      frequently caused an increase in the rate of ATP synthetic activity, while
      activity was reduced by deletions of a variety of functional genes, including
      many poorly characterized genes. We also demonstrated that the deletion of the
      ptsG gene doubled ATP-driven glutathione synthesis and increased cellular ATP
      synthetic activity. Our study also indicated that it should be easy to obtain
      active strains for ATP synthesis from deletion strains. Overall, the data set of
      this study may be useful to improve E. coli strains for ATP-dependent industrial
      processes and, therefore, may be important for the design of so-called cell
      factories.

PMID- 18718550
TI  - Serum platelet-activating factor acetylhydrolase activity: a novel potential
      inflammatory marker in type 1 diabetes.
AB  - Plasma activity of the platelet-activating factor acetylhydrolase (PAF-AH) plays
      an important role in inflammation and atherosclerotic process in chronic
      diseases. We aimed to evaluate the levels of PAF-AH activity and their
      association with the metabolic profile and chronic complications in patients with
      type 1 diabetes. The study included 118 outpatients (54 males) aged 27.1+/-11.3
      years with disease duration of 12.3+/-8.5 years with (n=38) or without (n=80)
      diabetes complications and 96 control subjects (48 males) matched for age,
      gender, body mass index and smoking habits. The serum levels of PAF-AH activity
      were higher in patients either with or without chronic complications (16+/-5.3
      and 14+/-5.4 nmol/(min mL), respectively) than in controls (13+/-5.1 nmol/(min
      mL), P=0.02). In the total population, PAF-AH activity was correlated with age,
      HDL-cholesterol, total cholesterol and LDL-cholesterol. In patients, PAF-AH
      activity was correlated with age, HbA1c, uric acid, HDL-cholesterol, cholesterol,
      LDL-cholesterol, cholesterol/HDL-cholesterol ratio and the LDL-cholesterol/HDL
      cholesterol ratio. It is concluded that PAF-AH plasma activity could be a novel
      candidate for low-grade inflammatory marker in patients with type 1 diabetes.

PMID- 18718551
TI  - Selenocystine induces caspase-independent apoptosis in MCF-7 human breast
      carcinoma cells with involvement of p53 phosphorylation and reactive oxygen
      species generation.
AB  - The role of selenium as potential cancer chemopreventive and chemotherapeutic
      agents has been supported by epidemiological, preclinical and clinical studies.
      Although cell apoptosis has been evidenced as a critical mechanism mediating the
      anticancer activity of selenium, the underlying molecular mechanisms remain
      elusive. In the present study, we showed that selenocystine (SeC), a naturally
      occurring selenoamino acid, induced caspase-independent apoptosis in MCF-7 breast
      carcinoma cells, which was accompanied by poly(ADP-ribose) polymerase (PARP)
      cleavage, caspase activation, DNA fragmentation, phosphatidylserine exposure and
      nuclear condensation. Moreover, SeC induced the loss of mitochondrial membrane
      potential (DeltaPsi(m)) by regulating the expression and phosphorylation of Bcl-2
      family members. Loss of DeltaPsi(m) led to the mitochondrial release of
      cytochrome c and apoptosis-inducing factor (AIF) which subsequently translocated
      into the nucleus and induced chromatin condensation and DNA fragmentation. MCF-7
      cells exposed to SeC shown increase in total p53 and phosphorylated p53 on serine
      residues of Ser15, Ser20, and Ser392 prior to mitochondrial dysfunction.
      Silencing and attenuating of p53 activation with RNA interference and pifithrin
      alpha treatment, respectively, partially suppressed SeC-induced cell apoptosis.
      Furthermore, generation of reactive oxygen species and subsequent induction of
      DNA strand breaks were found to be upstream cellular events induced by SeC. The
      thiol-reducing antioxidants, N-acetylcysteine and glutathione, completely blocked
      the occurrence of cell apoptosis. Taken together, these results suggest that SeC,
      as a promising anticancer selenocompound, induces MCF-7 cell apoptosis by
      activating ROS-mediated mitochondrial pathway and p53 phosphorylation.

PMID- 18718553
TI  - Formation of micronucleated erythrocytes in mouse bone-marrow under conditions of
      hypothermia is not associated with stimulation of erythropoiesis.
AB  - Conditions of marked and long-lasting hypothermia have been shown to increase the
      formation of micronucleated polychromatic erythrocyte (MNPCE) in mouse bone
      marrow. Stimulation of erythropoiesis as a consequence of anoxic conditions
      associated with decreased body temperature has been suggested as a possible
      mechanism for hypothermia-induced micronucleus formation. We examined whether
      chemically induced hypothermic conditions that produced increased MNPCE formation
      were associated with stimulation of erythropoiesis by measuring erythropoietin
      (EPO) concentrations in blood. Marked and long-lasting hypothermia was induced in
      male mice by oral administration of the antipsychotic compounds E-5842 (200
      mg/kg) or chlorpromazine (100 mg/kg). Maximum decreases from the basal
      temperature, achieved 8 h after treatment, were 14.8 and 12.8 degrees C,
      respectively. A statistically significant increase in bone-marrow MNPCE frequency
      was observed 48 h after administration of E-5842 (p<0.01) or chlorpromazine
      (p<0.05). Mice made anaemic by retro-orbital bleeding (0.5 ml), which acted as
      positive control for stimulation of erythropoiesis, showed no relevant variation
      in mean rectal temperature and a slight non-statistically significant increase in
      MNPCE frequency after 48 h. Blood samples for determination of EPO levels were
      obtained 4 (bleed-control animals only), 8, 16 and 24 h after treatment. In spite
      of the induced hypothermia, no significant variation in EPO blood levels was
      observed after administration of E-5842 or chlorpromazine. Bleed-induced anaemic
      mice showed a clear increase in EPO blood levels at all sampled time points,
      differences from baseline values being statistically significant (p<0.001) at the
      8-h samplings and beyond. These results indicate that induction of MNPCE
      secondary to chemically induced hypothermia is not mediated by stimulation of
      erythropoiesis.

PMID- 18718552
TI  - Mass spectrometry for proteomics.
AB  - Mass spectrometry has been widely used to analyze biological samples and has
      evolved into an indispensable tool for proteomics research. Our desire to
      understand the proteome has led to new technologies that push the boundary of
      mass spectrometry capabilities, which in return has allowed mass spectrometry to
      address an ever-increasing array of biological questions. The recent development
      of a novel mass spectrometer (Orbitrap) and new dissociation methods such as
      electron-transfer dissociation has made possible the exciting new areas of
      proteomic application. Although bottom-up proteomics (analysis of proteolytic
      peptide mixtures) remains the workhorse for proteomic analysis, middle-down and
      top-down strategies (analysis of longer peptides and intact proteins,
      respectively) should allow more complete characterization of protein isoforms and
      post-translational modifications. Finally, stable isotope labeling strategies
      have transformed mass spectrometry from merely descriptive to a tool for
      measuring dynamic changes in protein expression, interaction, and modification.

PMID- 18718554
TI  - Flow-cytometric analysis of in vitro micronucleus formation: comparative studies
      with WIL2-NS human lymphoblastoid and L5178Y mouse lymphoma cell lines.
AB  - The development of a flow cytometry-based micronucleus (FCMMN) assay for
      measuring the micronucleus (MN) frequency in cells following exposure to test
      chemicals has potential for improving reproducibility and reducing turn-around
      time when compared with the traditional microscopy-based micronucleus method. A
      major drawback of the FCMMN assay is that a false-positive interpretation could
      result from the presence of large numbers of apoptotic or necrotic bodies in the
      measured sample. Although several studies have reported ways in which the FCMMN
      assay could be improved using different staining techniques or electronic gating
      strategies, to date none of these protocols are suitable for use as a screening
      assay. To reduce the interference from apoptosis, performing the FCMMN assay with
      an apoptosis-resistant cell line may be an alternative approach. This study
      reports the use of p53-mutated cell lines to minimise the interference found in
      the FCMMN assay. Two commonly used cell lines (WIL2-NS and L5178Y) were
      investigated by comparison of (1) cytotoxicity and micronucleus induction in the
      FCMMN assay following treatment with model genotoxicants and (2) apoptotic
      responses after exposure to inducers of apoptosis. Both cell lines were
      responsive to all genotoxicants, producing concentration-dependent results with
      respect to genotoxicity. WIL2-NS cells were found to be more tolerant to
      apoptosis induction than L5178Y cells. This characteristic could be beneficial to
      minimise the interference from apoptotic nuclei in the FCMMN genotoxicity
      screening assay.

PMID- 18718555
TI  - Why is recruitment to trials difficult? An investigation into recruitment
      difficulties in an RCT of supported employment in patients with severe mental
      illness.
AB  - BACKGROUND: Under-recruitment to randomised controlled trials (RCTs) is often
      problematic and there may be particular difficulties in recruiting patients with
      severe mental illness. AIM: To evaluate reasons for under-recruitment in an RCT
      of patients with severe mental illness METHODS: Qualitative study during the
      recruitment phase of an RCT of supported employment. Trial staff and recruiting
      clinicians were interviewed. Data were analyzed thematically using constant
      comparative techniques. RESULTS: Recruitment rates were low. Five main reasons
      for recruitment difficulties were found. These included: (i) misconceptions about
      trials, (ii) lack of equipoise, (iii) misunderstanding of the trial arms, (iv)
      variable interpretations of eligibility criteria, (v) paternalism. CONCLUSION:
      Reasons for recruitment difficulties in trials involving patients with severe
      mental illness include issues that occur in trials in general, but others are
      more specific to these patients. Clinician and patient involvement in the study
      design may improve recruitment in future similar trials.

PMID- 18718556
TI  - Identifying subpopulations for subgroup analysis in a longitudinal clinical
      trial.
AB  - BACKGROUND: In a typical clinical trial treatment effects will not be expected to
      be the same on all of the study participants. As a result, investigators are
      often tempted to look at the effects of a given treatment in subgroups of
      patients in order to determine who will benefit the most or the least, especially
      when the treatment effect in the total sample is insignificant or borderline.
      This paper aims at demonstrating the application of random effect models as one
      approach to identify subpopulations suitable for subgroup analysis in a
      longitudinal study. METHODS: Data collected from a double-blind randomized
      controlled trial were used to demonstrate how multilevel modeling using random
      effects can be used to identify subgroups of postmenopausal women who benefit the
      most from nonhormonal treatment (gabapentin) of their hot flashes. RESULTS: We
      estimated subject-specific treatment effects and correlated these effects with
      patient characteristics at baseline. We found that women with a higher severity
      of hot flashes score at baseline were more likely to have the greatest reduction
      in hot flashes score from the treatment. Also, women who had a serum creatinine
      level higher than the median level at baseline demonstrated a greater response to
      gabapentin compared to the placebo group. CONCLUSION: Our proposed method can
      help researchers identify patient factors that are associated with differential
      effect. Those factors are potential areas for further clinical investigation or
      for constructing subgroups for sub-analysis.

PMID- 18718557
TI  - The evolution of Staphylococcus aureus.
AB  - A broad variety of infections, ranging from minor infections of the skin to post
      operative wound infections can be caused by Staphylococcus aureus. The adaptive
      power of S. aureus to antibiotics leaded, in the early 1960s, to the emergence of
      methicillin-resistant S. aureus (MRSA). The cause of resistance to methicillin
      and all other beta-lactam antibiotics is the mecA gene, which is situated on a
      mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec).
      Seven major variants of SCCmec, type I to VII, are distinguished. The most
      important techniques used to investigate the molecular epidemiology of S. aureus
      are pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST),
      S. aureus protein A (spa) typing and SCCmec typing (only for MRSA). These
      techniques have been used to study the evolution of the MRSA clones that have
      emerged since the early 1960s, and to study their subsequent worldwide
      dissemination. The early MRSA clones were hospital-associated (HA-MRSA). However,
      from the late 1990s, community-associated MRSA (CA-MRSA) clones emerged
      worldwide. CA-MRSA harbors SCCmec type IV, V or VII, the majority belong to other
      S. aureus lineages compared to HA-MRSA, and CA-MRSA is often associated with the
      presence of the toxin Panton-Valentine leukocidin (PVL). However, during recent
      years, the distinction between HA-MRSA and CA-MRSA has started to disappear, and
      CA-MRSA is now endemic in many US hospitals. MRSA probably originated trough the
      transfer of SCCmec into a limited number of methicillin-sensitive S. aureus
      (MSSA) lineages. This review describes the latest observations about the
      structure of SCCmec, the techniques used to study the molecular epidemiology and
      evolution of S. aureus as well as some challenges that researchers face in the
      future.

PMID- 18718558
TI  - Human dispersal of Trichinella spiralis in domesticated pigs.
AB  - To investigate the human impact on the evolutionary ecology of animal pathogens,
      we compared genetic diversity of severe foodborne parasites contracted by eating
      infected pork or wild game. In particular, we characterized Trichinella spp. from
      twenty-eight countries and four continents by genotyping nine microsatellite loci
      and sequencing one-fifth of the mitochondrial genome. All specimens of
      Trichinella spiralis, a swine parasite that can infect many species of wildlife,
      were remarkably uniform across Europe, North Africa, and the Americas. Far
      greater diversity characterized a comparable sample of Trichinella britovi, which
      parasitizes various sylvatic mammals endemic to Eurasia and North-Western Africa.
      A limited sample of T. spiralis in Asia, where swine were first domesticated,
      encompassed greater genetic variability than those in the West, as did small
      samples of Trichinella nativa and Trichinella murrelli, which parasitize wildlife
      hosts. We conclude that European lineages of T. spiralis originated several
      thousand years ago, approximately when pigs were first domesticated there. These
      data also imply that Europeans inadvertently introduced T. spiralis to the
      Americas via infected pigs and/or rats. Despite evidence that early hominid
      hunters ingested foodborne parasites by hunting wild game millions of years
      earlier, swine husbandry has governed the subsequent transmission, dissemination,
      and evolutionary diversification of T. spiralis. Where viable parasites have been
      eliminated from their diet, the residual risk posed to swine by exposure to
      wildlife or rats should be more precisely defined because breaking the cycle of
      transmission would confer enduring economic and health benefits.

PMID- 18718559
TI  - The evolution of foot-and-mouth disease virus: impacts of recombination and
      selection.
AB  - Foot-and-mouth disease virus is an economically important animal virus that
      exhibits extensive genetic and antigenic heterogeneity. To examine the
      evolutionary forces that have influenced the population dynamics of foot-and
      mouth disease virus, individual genes and the coding genomes for the Eurasian
      (Asia1, A, C, and O) serotypes were examined for phylogenetic relationships,
      recombination, genetic diversity and selection. Our analyses demonstrate that
      paraphyletic relationships among serotypes are not as prevalent as previously
      proposed and suggest that convergent evolution might be obscuring phylogenetic
      relationships. We provide evidence that identification of recombinant sequences
      and recombination breakpoint patterns among and within serotypes are heavily
      dependent on the level of genetic diversity and convergent characters present in
      a particular data set as well as the methods used to detect recombination. Here,
      we also investigate the impact of adaptive positive selection on the capsid
      proteins and the non-structural genes 2B, 2C, 3A, and 3Cpro to identify genome
      regions involved in genetic diversity and antigenic variation. Two different
      categories of positive selection at the amino acid level were examined;
      conservative (stabilizing) selection that maintains particular phenotypic
      properties of an amino acid residue and radical (destabilizing), and selection
      that dramatically alters the phenotype and potentially the functional and/or
      structural features of the protein. Approximately, 29% of residues in the capsid
      proteins were under positive selection. Of those, 64% were under the influence of
      destabilizing selection, 80% were under the influence of stabilizing selection,
      and 44% had phenotypic properties influenced by both selection types. The
      majority of residues under selection (74%) were located outside of known
      antigenic sites; suggestive of additional uncharacterized epitopes and genomic
      regions involved in antigenic drift.

PMID- 18718560
TI  - Clinical and genetic aspects of Blau syndrome: a 25-year follow-up of one family
      and a literature review.
AB  - Blau syndrome (BS) is a rare familial disease transmitted as an autosomal
      dominant trait, characterized by arthritis, uveitis, skin rash and granulomatous
      inflammation. Until now BS has been observed in 136 persons belonging to 28
      families as well as in 4 sporadic cases. The gene responsible for BS has recently
      been identified in the nucleotide-binding domain (NBD) of caspase recruitment
      domain (CARD15/NOD2), also involved in the pathogenesis of Crohn's disease. In
      addition to three missense mutations (R334Q, R334W and L469F) previously
      identified, a new CARD 15 mutation (E383K) has recently been described in a
      family followed by us for the past 25 years. The characteristics of this family
      which, to our knowledge, is the only one affected with BS in Italy, are the
      object of this manuscript. Both the proband and her daughter were originally
      affected with a papulonodular skin eruption and then with mild arthritis of the
      hands and feet. The proband, but not the daughter, complained of severe chronic
      bilateral uveitis, followed by glaucoma and, a few years later, by cataracts.
      Histological examination of skin biopsies from both subjects and a joint biopsy
      (daughter only), showed non-caseating granulomas with multinucleated giant cells
      which, at electron microscopy, revealed "comma-shaped bodies" in epithelioid
      cells, thought to be a marker for BS. The disease is presently well controlled
      with low doses of prednisone for the mother and non-steroidal anti-inflammatory
      drugs (NSAIDs) plus low doses of prednisone, when necessary, for the daughter. As
      in Crohn's disease, CARD15/NOD2 mutation is believed to be responsible for the
      granulomatous autoinflammatory reactions probably triggered by microorganisms in
      BS.

PMID- 18718561
TI  - Interleukin (IL)-1 regulates ozone-enhanced tracheal smooth muscle responsiveness
      by increasing substance P (SP) production in intrinsic airway neurons of ferret.
AB  - Exposure to ozone induces airway hyperresponsiveness (AHR) mediated partly by
      substance P (SP) released from nerve terminals of intrinsic airway neurons. Our
      recent studies showed that interleukin (IL)-1, an important multifunctional
      proinflammatory cytokine, increases synthesis and release of SP from intrinsic
      airway neurons. The purpose of this study is to investigate the possible
      involvement of endogenous IL-1 in modulating neural responses associated with
      ozone-enhanced airway responsiveness. Ferrets were exposed to 2ppm ozone or
      filtered air for 3h. IL-1 in the bronchoalveolar lavage (BAL) fluid was
      significantly increased in ozone-exposed animals and responses of tracheal smooth
      muscle to methacholine (MCh) and electrical field stimulation (EFS) were elevated
      significantly. Both the SP nerve fiber density in tracheal smooth muscle and the
      number of SP-containing neurons in airway ganglia were significantly increased
      following ozone exposure. Pretreatment with IL-1 receptor antagonist (IL-1 Ra)
      significantly diminished ozone-enhanced airway responses to EFS as well as ozone
      increased SP in the airway. To selectively investigate intrinsic airway neurons,
      segments of ferret trachea were maintained in culture conditions for 24h to
      eliminate extrinsic contributions from sensory nerves. The segments were then
      exposed to 2ppm ozone in vitro for 3h. The changes of ozone-induced airway
      responses to MCh and EFS, and the SP levels in airway neurons paralleled those
      observed with in vivo ozone exposure. The ozone-enhanced airway responses and
      neuronal SP levels were inhibited by pretreatment with IL-1 Ra. These findings
      show that IL-1 is released during ozone exposure enhances airway responsiveness
      by modulating SP expression in airway neurons.

PMID- 18718563
TI  - Structure of mistletoe lectin I from Viscum album in complex with the
      phytohormone zeatin.
AB  - The crystal structure of mistletoe lectin I (ML-I) isolated from the European
      mistletoe Viscum album in complex with the most active phytohormone zeatin has
      been analyzed and refined to 2.54 A resolution. X-ray suitable crystals of ML-I
      were obtained by the counter-diffusion method using the Gel-Tube R
      crystallization kit (GT-R) onboard the Russian Service Module on the
      international space station ISS. High quality hexagonal bipyramidal crystals were
      grown during 3 months under microgravity conditions. Selected crystals were
      soaked in a saturated solution of zeatin and subsequently diffraction data were
      collected applying synchrotron radiation. A distinct F(o)-F(c) electron density
      has been found inside a binding pocket located in subunit B of ML-I and has been
      interpreted as a single zeatin molecule. The structure was refined to investigate
      the zeatin-ML-I interactions in detail. The results demonstrate the ability of
      mistletoe to protect itself from the host transpiration regulation by absorbing
      the most active host plant hormones as part of a defense mechanism.

PMID- 18718564
TI  - Proteomics applied on plant abiotic stresses: role of heat shock proteins (HSP).
AB  - The most crucial function of plant cell is to respond against stress induced for
      self-defence. This defence is brought about by alteration in the pattern of gene
      expression: qualitative and quantitative changes in proteins are the result,
      leading to modulation of certain metabolic and defensive pathways. Abiotic
      stresses usually cause protein dysfunction. They have an ability to alter the
      levels of a number of proteins which may be soluble or structural in nature.
      Nowadays, in higher plants high-throughput protein identification has been made
      possible along with improved protein extraction, purification protocols and the
      development of genomic sequence databases for peptide mass matches. Thus, recent
      proteome analysis performed in the vegetal Kingdom has provided new dimensions to
      assess the changes in protein types and their expression levels under abiotic
      stress. As reported in this review, specific and novel proteins, protein-protein
      interactions and post-translational modifications have been identified, which
      play a role in signal transduction, anti-oxidative defence, anti-freezing, heat
      shock, metal binding etc. However, beside specific proteins production, plants
      respond to various stresses in a similar manner by producing heat shock proteins
      (HSPs), indicating a similarity in the plant's adaptive mechanisms; in plants,
      more than in animals, HSPs protect cells against many stresses. A relationship
      between ROS and HSP also seems to exist, corroborating the hypothesis that during
      the course of evolution, plants were able to achieve a high degree of control
      over ROS toxicity and are now using ROS as signalling molecules to induce HSPs.

PMID- 18718562
TI  - Partitioned exhaled nitric oxide to non-invasively assess asthma.
AB  - Asthma is a chronic inflammatory disease of the lungs, characterized by airway
      hyperresponsiveness. Chronic repetitive bouts of acute inflammation lead to
      airway wall remodeling and possibly the sequelae of fixed airflow obstruction.
      Nitric oxide (NO) is a reactive molecule synthesized by NO synthases (NOS). NOS
      are expressed by cells within the airway wall and functionally, two NOS isoforms
      exist: constitutive and inducible. In asthma, the inducible isoform is over
      expressed, leading to increased production of NO, which diffuses into the airway
      lumen, where it can be detected in the exhaled breath. The exhaled NO signal can
      be partitioned into airway and alveolar components by measuring exhaled NO at
      multiple flows and applying mathematical models of pulmonary NO dynamics. The
      airway NO flux and alveolar NO concentration can be elevated in adults and
      children with asthma and have been correlated with markers of airway inflammation
      and airflow obstruction in cross-sectional studies. Longitudinal studies which
      specifically address the clinical potential of partitioning exhaled NO for
      diagnosis, managing therapy, and predicting exacerbation are needed.

PMID- 18718565
TI  - Minodronic acid (ONO-5920/YM529) prevents decrease in bone mineral density and
      bone strength, and improves bone microarchitecture in ovariectomized cynomolgus
      monkeys.
AB  - This study examined the effect of the highly potent nitrogen-containing
      bisphosphonate, minodronic acid (ONO-5920/YM529), on bone mineral density (BMD),
      bone turnover, bone microarchitecture and bone strength in ovariectomized (OVX)
      cynomolgus monkeys. Skeletally mature female cynomolgus monkeys, aged 9-17 years,
      were ovariectomized or sham-operated. Minodronic acid was administered orally
      once a day in doses of 0, 0.015, and 0.15 mg/kg from the day after surgery for 17
      months. Bone resorption markers (urinary N-terminal cross-linking telopeptide of
      type I collagen and deoxypyridinoline), bone formation markers (serum osteocalcin
      and bone alkaline phosphatase) and lumbar vertebral BMD were measured at baseline
      and at 4, 8, 12 and 16 months after surgery. Treatment with minodronic acid dose
      dependently inhibited OVX-induced increase in bone turnover markers and decrease
      in lumbar vertebral BMD, and minodronic acid at 0.15 mg/kg completely prevented
      these changes. At 17 months after surgery, minodronic acid also suppressed bone
      resorption (Oc.S/BS and N.Oc/BS) and bone formation (OS/BS, MS/BS, MAR, BFR/BS,
      and BFR/BV) in the lumbar vertebral bodies and tibia. In the mechanical tests,
      ultimate load on lumbar vertebral bodies and femoral neck of the OVX-control
      animals were significantly reduced compared to the sham animals. Minodronic acid
      prevented these reductions in bone strength at 0.15 mg/kg. There was significant
      correlation between BMD and bone strength, suggesting that the increase in bone
      strength was associated with the increase in BMD produced by minodronic acid. In
      micro-CT analysis of the lumbar vertebral bodies, minodronic acid improved
      trabecular architecture, converting rod structures into plate structures, and
      preventing the increase in trabecular disconnectivity at 0.15 mg/kg. In
      conclusion, similar to patients with postmenopausal osteoporosis, reduction in
      bone strength of lumbar vertebral bodies and femoral neck was clearly
      demonstrated in OVX cynomolgus monkeys. Minodronic acid prevented these
      reductions at a once-daily oral administration. Also, minodronic acid prevented
      OVX-induced changes in bone turnover, bone mass and bone microarchitecture. Long
      term minodronic acid treatment was well tolerated and no adverse effects could be
      detected. These results suggest that minodronic acid may be a clinically useful
      drug for osteoporosis.

PMID- 18718566
TI  - IGF-I secreted by osteoblasts acts as a potent chemotactic factor for
      osteoblasts.
AB  - Osteoblast recruitment to the site of future bone formation is essential for
      skeletal development, bone remodeling and fracture healing. A number of factors
      associated with bone tissue have been reported to induce directional migration of
      osteoblasts but the mechanism remains to be clarified. In this study, to explore
      a major chemotactic factor(s) for osteoblasts, we examined the serum-free medium
      conditioned by MC3T3-E1 osteoblast-like cells for its ability to induce
      osteoblast migration. Employing sequential chromatography and tandem mass
      spectrometry analysis, we purified and identified IGF-I as a potent chemotactic
      factor from the conditioned medium. IGF-I induced cell migration of both MC3T3-E1
      cells and primary mouse osteoblasts, and checkerboard analysis revealed that IGF
      I markedly induced directional migration (chemotaxis) of osteoblasts.
      Neutralization of mouse IGF-I with monoclonal antibodies resulted in delayed
      osteoblast monolayer wound healing and cellular polarization but addition of
      human IGF-I reversed these effects. IGF-I also promoted cell spreading on
      fibronectin in an integrin beta1-dependent manner. IGF-I induced Akt and Rac
      activation and localized accumulation of phosphatidylinositol 3,4,5-triphosphate
      (PtdIns (3,4,5)P3) at the membrane in osteoblasts. The phosphatidyl inositol 3
      kinase (PI3K) inhibitor LY294002 inhibited IGF-I-induced cell migration and wound
      healing. Together, the results suggest that IGF-I secreted from osteoblasts in
      the bone tissue is a potent chemotactic factor that may play a major role in
      recruitment of osteoblasts during bone formation.

PMID- 18718567
TI  - Reoperation rate following prolapse surgery.

PMID- 18718568
TI  - The 24-hour urine collection: gold standard or historical practice?
AB  - OBJECTIVE: The objective of the study was to determine completeness of 24-hour
      urine collection in pregnancy. STUDY DESIGN: This was a retrospective
      laboratory/chart review of 24-hour urine collections at British Columbia Women's
      Hospital. Completeness was assessed by 24-hour urinary creatinine excretion
      (UcreatV): expected according to maternal weight for single collections and
      between-measurement difference for serial collections. RESULTS: For 198 randomly
      selected pregnant women with a hypertensive disorder (63% preeclampsia), 24-hour
      urine collections were frequently inaccurate (13-54%) on the basis of UcreatV of
      97-220 micromol/kg per day (11.0-25.0 mg/kg per day) or 133-177 micromol/kg per
      day (15.1-20.1 mg/kg per day) of prepregnancy weight (respectively). Lean body
      weight resulted in more inaccurate collections (24-68%). The current weight was
      frequently unavailable (28%) and thus not used. For 161 women (81% proteinuric)
      with serial 24-hour urine levels, a median [interquartile range] of 11 [5-31]
      days apart, between-measurement difference in UcreatV was 14.4% [6.0-24.9]; 40
      women (24.8%) had values 25% or greater, exceeding analytic and biologic
      variation. CONCLUSION: Twenty-four hour urine collection is frequently inaccurate
      and not a precise measure of proteinuria or creatinine clearance.

PMID- 18718569
TI  - QuantiFERON TB-Gold--a new test strengthening long-suspected tuberculous
      involvement in serpiginous-like choroiditis.
AB  - PURPOSE: To obtain a diagnosis of tuberculosis in patients with a specific subset
      of uveitis, serpiginous-like choroiditis. This subset has been suspicious for
      tuberculous etiology in single case reports and old textbooks. DESIGN:
      Retrospective evaluation of a diagnostic test in a specific uveitis cohort.
      METHODS: QuantiFERON is an approved, antigen-specific test that utilizes
      synthetic peptides representing Mycobacterium tuberculosis proteins. After
      incubation, interferon gamma secreted by T lymphocytes in response to these
      antigens is measured. We used the test in 21 of 26 patients identified from our
      database with serpiginous-like choroiditis. Rates of QuantiFERON positivity were
      compared to a group of healthy hospital employees (n = 208), another group of
      healthy hospital workers after tuberculosis contact (n = 117), and a group of
      randomly tested patients with other uveitis forms (n = 45). RESULTS: Eleven of 21
      serpiginous-like choroiditis patients (52%) were tested positive. The rate of
      QuantiFERON positivity in the healthy control groups was 8.7% and 0.9%, and 13%
      in the other uveitis subsets. Four of the QuantiFERON-positive serpiginous-like
      choroiditis patients were treated with standard anti-tuberculostatic therapy;
      three finished the course and improved. Seven patients are either stable without
      therapy (n = 4) or on low-dose prednisone (n = 3). CONCLUSIONS: QuantiFERON
      testing revealed a high number of positive patients, which indicates a
      tuberculous etiology in this uveitis subset. Whether bacterial activity or
      secondary immunologic processes are causative remains a matter of speculation.

PMID- 18718570
TI  - Intravenous thrombolysis with low-dose recombinant tissue plasminogen activator
      in central retinal artery occlusion.
AB  - PURPOSE: To evaluate the beneficial effect of intravenous thrombolysis aiming at
      rapid restoration of blood flow during the early hours of a central retinal
      artery occlusion (CRAO). DESIGN: Interventional case series. METHODS: In the
      present study, we prospectively evaluated the visual outcome after thrombolytic
      treatment with low-dose (50 mg) rt-PA (recombinant tissue plasminogen activator)
      and concomitant intravenous heparinization in patients with acute CRAO, best
      corrected visual acuity (BCVA) < or = 20/100, and onset of symptoms within 12
      hours prior to treatment. RESULTS: Twenty-eight patients (28 eyes) were included
      in this study. Final visual acuity was improved three or more lines in nine eyes
      (32%), stable in 18 (64%), and worse in one eye. Time to treatment < or = 6.5
      hours was associated with a better gain of lines of vision (P = .004). Seven of
      17 eyes (41%) that received thrombolytic treatment within the first 6.5 hours
      achieved a final BCVA > or = 20/50, compared to none in the subgroup of patients
      with onset to treatment >6.5 hours (P = .023). We observed no serious adverse
      events. CONCLUSIONS: Our findings indicate that thrombolytic treatment with
      intravenous low-dose rt-PA is of value for an improved visual recovery in
      patients with acute CRAO, if administered within the first 6.5 hours after the
      onset of symptoms.

PMID- 18718571
TI  - Severely depressed young patients have over five times increased risk for stroke:
      a 5-year follow-up study.
AB  - BACKGROUND: This study aims to estimate the risk of developing stroke within 5
      years of discharge among young patients ages 18 to approximately 44 who were
      hospitalized for depressive disorders. METHODS: Our study design features a study
      cohort and a comparison cohort. The study cohort included patients ages 18 to
      approximately 44 who were hospitalized with a principal diagnosis of depressive
      disorder (n = 827), whereas the comparison cohort consisted of 4,135 patients
      selected randomly (five for every depressed patient) and matched with the study
      group in terms of gender, age, and date of discharge. Each patient was tracked
      for 5 years after their discharge in 1998. Cox proportional hazard regressions
      were performed to compute the 5-year stroke-free survival rates after adjusting
      for possible confounding factors. RESULTS: During the 5-year follow-up period, 50
      depressed patients (6.05% of the study cohort) and 48 non-depressed subjects
      (1.16% of the comparison cohort) developed strokes. The adjusted hazard of stroke
      was 5.43 (95% confidence interval = 3.47-8.51, p < .001) times greater for
      depressed patients than for non-depressed subjects. CONCLUSIONS: Our findings
      show young patients ages 18 to approximately 44 who were hospitalized for
      depressive disorders were at over five times greater risk of developing stroke
      within 5 years of discharge compared with non-depressed age- and gender-matched
      subjects.

PMID- 18718572
TI  - Optimizing the design and analysis of clinical functional magnetic resonance
      imaging research studies.
AB  - With the widespread availability of functional magnetic resonance imaging (fMRI),
      there has been rapid progress in identifying neural correlates of cognition and
      emotion in the human brain. In conjunction with basic research studies, fMRI has
      been increasingly applied in clinical disorders, making it a central research
      tool in human psychopathology, psychopharmacology, and genetics. In the present
      article, we discuss a number of conceptual and methodological challenges that
      confront the implementation of fMRI in clinical and translational research, and
      we offer a set of recommendations intended to enhance the interpretability and
      reproducibility of results in clinical fMRI.

PMID- 18718573
TI  - Neural hyporesponsiveness and hyperresponsiveness during immediate and delayed
      reward processing in adult attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Dysfunctional reward processing, accompanied by a limited ability to
      tolerate reward delays, has been proposed as an important feature in attention
      deficit/hyperactivity disorder (ADHD). METHODS: Using functional magnetic
      resonance imaging (fMRI), brain activation in adult patients with ADHD (n=14) and
      healthy control subjects (n=12) was examined during a series of choices between
      two monetary reward options that varied by delay to delivery. RESULTS: Compared
      with healthy control subjects, hyporesponsiveness of the ventral-striatal reward
      system was replicated in patients with ADHD and was evident for both immediate
      and delayed rewards. In contrast, delayed rewards evoked hyperactivation in
      dorsal caudate nucleus and amygdala of ADHD patients. In both structures, neural
      activity toward delayed rewards was significantly correlated with self-rated ADHD
      symptom severity. CONCLUSIONS: The finding of ventral-striatal hyporesponsiveness
      during immediate and delayed reward processing in patients with ADHD further
      strengthens the concept of a diminished neural processing of rewards in ADHD.
      Hyperactivation during delayed reward processing, gradually increasing along the
      ventral-to-dorsal extension of the caudate nucleus, and especially the
      concomitant hyperactivation of the amygdala are in accordance with predictions of
      the delay aversion hypothesis.

PMID- 18718574
TI  - Regarding "N-acetyl cysteine as a glutathione precursor for schizophrenia--a
      double-blind, randomized, placebo-controlled trial".

PMID- 18718575
TI  - Meta-analysis of brain volume changes in obsessive-compulsive disorder.
AB  - BACKGROUND: Many neuroimaging studies exploring the volumes of brain structures
      in obsessive-compulsive disorder (OCD) have been published in the past 2 decades.
      In this study, we attempted to provide a complete overview of structural
      alterations in OCD by meta-analyzing magnetic resonance imaging (MRI) data.
      METHODS: We conducted a systematic search of MRI studies that reported volumetric
      measurements in both OCD patients and healthy subjects. Data were entered into
      the meta-analysis through calculation of the standardized mean differences (SMDs)
      between the volumes of cerebral regions in OCD patients and the corresponding
      volumes in control subjects. We then performed a meta-regression to explore the
      influence of clinical covariates on effect sizes. RESULTS: Although no volumetric
      differences were found for the whole brain, intracranial region, gray matter, or
      prefrontal cortex, OCD patients did show a reduced volume of the left anterior
      cingulate cortex (ACC) and the left and right orbitofrontal cortex (OFC). No
      significant volumetric differences within the basal ganglia were observed,
      although the left and right thalamic volumes were significantly increased in OCD
      patients. The severity of obsessive or compulsive symptoms correlated
      significantly with the effect sizes for the left and right thalamus. CONCLUSIONS:
      Our findings indicate volumetric differences between OCD patients and control
      subjects in the cortical and thalamic regions, suggesting that structural
      alteration of the thalamocortical pathways may contribute to the functional
      disruptions of frontosubcortical circuits observed in OCD.

PMID- 18718576
TI  - Regioselective ring opening of benzylidene acetal protecting group(s) of
      hexopyranoside derivatives by DIBAL-H.
AB  - The reductive ring-opening reaction of benzylidene-protected glucosides and
      mannosides such as methyl 2,3-di-O-benzyl-4,6-O-benzylidene-alpha-d-glucoside (1)
      and methyl 2,3-di-O-benzyl-4,6-O-benzylidene-alpha-d-mannoside (4) by using a
      toluene stock solution of DIBAL-H and a dichloromethane stock solution of DIBAL-H
      gives mainly or selectively the corresponding 2,3,4-tri-O-benzyl derivatives (2,
      5) and 2,3,6-tri-O-benzyl derivatives (3, 6), respectively, although that of
      methyl 2,3-di-O-benzyl-4,6-O-benzylidene-alpha-d-galactoside (7) gives methyl
      2,3,6-tri-O-benzyl-alpha-d-galactoside (9) selectively irrespective of the
      solvent of the stock solution of DIBAL-H. Similarly, the reaction of the exo
      isomer of methyl 2,3:4,6-di-O-benzylidene-alpha-d-mannopyranosides (exo-10) with
      a toluene stock solution and dichloromethane stock solutions of DIBAL-H
      selectively gives methyl 3-O-benzyl-4,6-O-benzylidene-alpha-d-mannoside (12) and
      methyl 2-O-benzyl-4,6-O-benzylidene-alpha-d-mannoside (11), respectively,
      although that of endo-10 selectively affords 11, irrespective of the solvent of
      the stock solution of DIBAL-H.

PMID- 18718577
TI  - First isolation and structural determination of cyclic beta-(1-->2)-glucans from
      an alga, Chlorella pyrenoidosa.
AB  - The aqueous extract of the edible green microalgae Chlorella pyrenoidosa is of
      interest because of its immunostimulatory activity. Some components in the
      extract have been identified previously, namely a unique type of arabinogalactan
      and a galactofuran. Further fractionation of this extract was accomplished by
      treating the aqueous solution of the fraction precipitated by addition of 1.5vol
      of 95% ethanol with cetyltrimethylammonium bromide. The residue obtained by
      concentration of the supernatant was fractionated further by anion-exchange
      chromatography and size-exclusion chromatography on Sephadex G-100. Two fractions
      from the latter column were retained, of which one was a starch-like alpha-(1-
      >4)-linked d-glucan with some alpha-(1-->6) branches, and the other contained a
      starch plus a mixture of beta-(1-->2)-d-glucans. ESI mass spectrometry was used
      to show that the mixture contained both cyclic and linear beta-(1-->2)-d-glucans
      in a cyclic:linear ratio of 64:36, based on intensities of mass spectral peaks.
      For the cyclic beta-(1-->2)-d-glucans, ring sizes ranged from 18 to 35
      monosaccharides with the ring containing 21 glucose units (54% of the cyclic
      glucans) being greater than three times more abundant than the next most abundant
      component, the ring containing 22 glucose units (15%). No rings containing 20
      glucose units were present. This is the first observation of cyclic beta-(1-->2)
      d-glucans in algae, as far as we are aware. For the linear beta-(1-->2)-d
      glucans, the component containing 20 glucoses was most abundant (35% of the
      linear glucans), while the component containing 21 glucose units was the next
      most abundant (17%). These relatively low-molecular-weight glucans had low
      immunostimulatory activity.

PMID- 18718579
TI  - Coordination of gaze and hand movements for tracking and tracing in 3D.
AB  - In this study we have investigated movements in three-dimensional space. Since
      most studies have investigated planar movements (like ellipses, cloverleaf shapes
      and "figure eights") we have compared two generalizations of the two-thirds power
      law to three dimensions. In particular we have tested whether the two-thirds
      power law could be best described by tangential velocity and curvature in a plane
      (compatible with the idea of planar segmentation) or whether tangential velocity
      and curvature should be calculated in three dimensions. We defined total
      curvature in three dimensions as the square root of the sum of curvature squared
      and torsion squared. The results demonstrate that most of the variance is
      explained by tangential velocity and total curvature. This indicates that all
      three orthogonal components of movements in 3D are equally important and that
      movements are truly 3D and do not reflect a concatenation of 2D planar movement
      segments. In addition, we have studied the coordination of eye and hand movements
      in 3D by measuring binocular eye movements while subjects move the finger along a
      curved path. The results show that the directional component and finger position
      almost superimpose when subjects track a target moving in 3D. However, the
      vergence component of gaze leads finger position by about 250msec. For drawing
      (tracing) the path of a visible 3D shape, the directional component of gaze leads
      finger position by about 225msec, and the vergence component leads finger
      position by about 400msec. These results are compatible with the idea that gaze
      leads hand position during drawing movement to assist prediction and planning of
      hand position in 3D space.

PMID- 18718578
TI  - The persistence of spatial interference after extended training in a bimanual
      drawing task.
AB  - Many studies of bimanual coordination have focused on the pervasive interference
      observed when people plan and produce non-symmetric movements. We investigated
      how the interference observed in one challenging bimanual task, simultaneously
      drawing non-symmetric three-sided squares (e.g., U and C), is modulated by
      practice. We assessed whether the benefits of practice were limited to the
      trained patterns or reflected the development of a more general ability for
      independently controlling movements of the two hands. We combined four
      orientations of a three-sided square, with one orientation assigned to each hand,
      to generate a set of 16 patterns. Participants were trained for six days with
      eight of the patterns. In the last two sessions, all 16 patterns were tested. The
      untrained patterns involved a shape that had not been practiced by one hand or a
      novel configuration of two practiced components. While a substantial reduction in
      inter-manual interference was observed over the extensive training period,
      participants remained much slower to plan incongruent shapes compared to
      congruent shapes. Incomplete generalization was observed when the new patterns
      were introduced. Planning time was shorter and accuracy higher for the trained
      patterns, but this effect was only observed in the first generalization session.
      There was little difference in performance between new patterns that involved an
      unpracticed shape or an unpracticed configuration. These results indicate that
      spatial interference was not eliminated with extensive practice. This persistent
      interference effect stands in contrast to the minimal interference observed when
      the gestures are conceptualized as a single action or do not involve the
      transformation of abstract spatial codes. The results suggest that a primary
      difficulty in bimanual drawing results from limitations in translating abstract
      goals into actions, a fundamental prerequisite for praxis.

PMID- 18718580
TI  - Representational neglect in "invisible" drawing from memory.
AB  - We describe the case of a patient with right hemisphere damage and left
      unilateral neglect. The patient was asked to draw from memory common objects,
      either with or without visual feedback. In the conditions without visual feedback
      the patient was either blindfolded or he made "invisible" drawings using a pen
      with the cap on, the drawings being recorded with carbon paper underneath.
      Results showed more neglect without than with visual feedback, contrary to
      previously published cases. This patient's pattern of performance may result from
      the contribution of a deficit of spatial working memory. Alternatively or in
      addition, the patient, who was undergoing cognitive rehabilitation for neglect,
      may have found easier to compensate for his neglect with visual feedback, which
      allowed him to visually explore the left part of his drawings.

PMID- 18718581
TI  - Clinical use of colony-stimulating factor-1 in ovulation induction for poor
      responders.
AB  - OBJECTIVE: To evaluate the benefit of colony-stimulating factor-1 (CSF-1)
      adjuvant therapy to poor responders during a controlled ovarian hyperstimulation
      (COH) cycle. DESIGN: Prospective clinical study. SETTING: University hospital,
      general hospital, and private IVF clinic in Japan. PATIENT(S): Thirty
      normogonadotropic patients who did not respond to conventional COH protocols.
      INTERVENTION(S): Eight million units of recombinant human CSF-1 were administered
      IV every other day during ovarian stimulation using FSH or hMG to 30
      normogonadotropic poor responders. Serum CSF-1 concentrations were assayed on day
      3. Additional studies were performed in a private IVF clinic on 27 poor
      responders with low serum CSF-1 levels. MAIN OUTCOME MEASURE(S): Pregnancy rates
      (PR). In addition, number of mature follicles, cycle cancellations, amount of
      required gonadotropins were documented. RESULT(S): Significantly more mature
      follicles, fewer cycle cancellations, and lower amounts of required gonadotropins
      were seen in the group treated with CSF-1. Five (16.7%) pregnancies were
      achieved. The CSF-1-effective patients displayed significantly lower serum CSF-1
      concentrations. In a private IVF clinic, CSF-1 treatment increased the number of
      mature oocytes, fertilized eggs, and transferred embryos. Cycle cancellations
      decreased from 18.5%-3.7%; 11 pregnancies (40.7%) resulted from treatment.
      CONCLUSION(S): Concomitant administration of CSF-1 and hMG improved follicle
      developments, especially in patients with low serum CSF-1 levels in the early
      follicular phase.

PMID- 18718582
TI  - Impact of blastocyst transfer on offspring sex ratio and the monozygotic twinning
      rate: a systematic review and meta-analysis.
AB  - OBJECTIVE: To determine the sex ratio and risk of monozygotic twinning (MZT)
      after blastocyst transfer compared with cleavage-stage embryo transfer (ET) in
      fresh IVF cycles. DESIGN: Systematic review and meta-analysis. SETTING:
      University hospital center for reproductive medicine and IVF. PATIENT(S): Results
      of all reports from January 1995 to November 2007 with women undergoing nondonor
      fresh IVF. The sex ratio of 2,587 offspring and MZT rate in 40,917 cycles were
      included. INTERVENTION(S): Cleavage or blastocyst stage for embryo transfer. MAIN
      OUTCOME MEASURE(S): Sex ratio and rate of MZT. RESULT(S): A meta-analysis was
      performed using four studies for sex ratio and nine studies for MZT. The results
      of the meta-analysis using a fixed effect model demonstrated a higher male-female
      ratio after blastocyst transfer compared with cleavage-stage ET (odds ratio [OR]
      1.29, 95% confidence interval [CI] 1.10-1.51), and this difference was
      statistically significant. The risk of MZT after blastocyst transfer was
      significantly higher compared with cleavage-stage ET (OR 3.04, 95% CI 1.54-6.01).
      CONCLUSION(S): The combined data presented in this meta-analysis suggest that
      blastocyst transfer appears to be associated with a sex ratio skewed in favor of
      males and an increased risk of MZT. The clinicians should provide this
      information to their infertility patients awaiting blastocyst transfer.

PMID- 18718583
TI  - Intravenous proton pump inhibition utilization and prescribing patterns
      escalation: a comparison between early and current trends in use.
AB  - BACKGROUND: Approved indications of intravenous (i.v.) proton pump inhibition
      (PPI) are limited to treatment of reflux esophagitis in patients unable to
      tolerate oral medications and for patients with pathologic hypersecretory states.
      OBJECTIVES: i.v. PPIs are commonly used after endoscopic evaluation of patients
      with high-risk endoscopic stigmata (HRES) of nonvariceal upper GI bleeding
      (NVUGIB). There appears to have been an expansion of indications of this drug at
      many centers. DESIGN: All consecutive patients receiving i.v. PPI (pantoprazole)
      between 2 study periods, (1) when pantoprazole was restricted to the
      gastroenterology service and (2) when it was unrestricted, were reviewed.
      SETTING: Tertiary care university hospital. PATIENTS: All receiving i.v. PPI.
      INTERVENTIONS: i.v. PPI utilization. MAIN OUTCOME MEASUREMENTS: Percentage of
      patients receiving i.v. PPI for indications other than bleeding during 2 time
      periods. RESULTS: In the early period, 217 patients (67.30% male) received i.v.
      PPI on 218 occasions compared with 516 patients (65.31% male, P= .61) in the
      later period on 613 occasions. In the early group, 93.12% of 217 patients
      received i.v. PPI for NVUGIB compared with 56.12% of 516 patients (P< .0001) with
      18% of patients receiving i.v. PPI for nothing by mouth status and 13% for
      abdominal pain in the later group. A total of 153 (70.18%) patients in the early
      group underwent upper endoscopy compared with only 275 (44.86%) patients in the
      later group; 84 of these 153 patients (54.90%) were already on i.v. PPI at the
      time of endoscopy in the early group compared with 253 (92.00%, P< .0001).
      CONCLUSIONS: i.v. PPI use has escalated at our hospital and is being prescribed
      in patients before endoscopy with fewer patients noted to have HRES on endoscopy.

PMID- 18718584
TI  - Quantitative analysis of the color change after iodine staining for diagnosing
      esophageal high-grade intraepithelial neoplasia and invasive cancer.
AB  - BACKGROUND: Despite its high sensitivity for detecting esophageal cancer,
      chromoendoscopy with iodine staining has low specificity and requires many biopsy
      specimens, which is undesirable. Dramatic color change after iodine staining
      (initially whitish yellow and then pink 2 to 3 minutes later) has come to be
      recognized as the pink-color sign in cancerous lesions. OBJECTIVE: The aim of the
      present study was to verify the accuracy of the pink-color sign for diagnosing
      esophageal squamous neoplasms by a quantitative analysis. DESIGN: A quantitative
      analysis of endoscopic images was performed by using prospectively pooled data.
      SETTING: A cancer referral center. PATIENTS: From December 2003 to September
      2005, consecutive patients who underwent a procedure by an experienced
      endoscopist and had iodine-unstained lesions measuring 5 to 20 mm in diameter
      without obvious protrusions or ulcers were prospectively enrolled. MAIN OUTCOME
      MEASUREMENTS: The diagnostic ability of the quantitative assessment of the color
      change at 2 minutes after iodine staining (late phase) was investigated by using
      a receiver operating characteristic analysis. RESULTS: A total of 45 iodine
      unstained lesions in 32 patients were included in the study. Among these, 22 of
      23 pink-color-positive lesions were diagnosed as high-grade intraepithelial
      neoplasias or invasive cancers, whereas 19 of 22 pink-color-negative lesions were
      diagnosed as nonneoplastic lesions or low-grade intraepithelial neoplasias. The
      area under the receiver operating characteristic curve was 0.94, indicating
      excellent validity of the test. A sensitivity of 88% and specificity of 95% were
      obtained. LIMITATIONS: Single-center retrospective analysis. CONCLUSIONS: We
      verified the accuracy of the pink-color sign for diagnosing esophageal squamous
      neoplasms by a quantitative analysis.

PMID- 18718585
TI  - Feasibility of gastric electrical stimulation by percutaneous endoscopic
      transgastric electrodes.
AB  - BACKGROUND: Gastric electrical stimulation has been used for the treatment of
      drug refractory GI motility disorders and for the treatment of obesity. Both
      these indications have involved surgical placement of gastric electrodes, which
      adds to the complexity and cost of the procedure. Endoscopic placement is
      therefore an attractive alternative approach for this therapy. OBJECTIVE: Our
      purpose was to investigate the feasibility, safety, and efficacy of percutaneous
      endoscopic electrodes for gastric electrical stimulation. DESIGN AND SETTING:
      Experimental animal study in hound dogs. INTERVENTIONS: Percutaneous endoscopic
      transgastric electrode (PETE) placement was carried out by using a pair of
      gastric pacing wires attached to a percutaneous endoscopic gastrostomy tube. In
      addition, 4 pairs of gastric serosal electrodes were implanted surgically for
      comparison. The efficacy of the percutaneous endoscopic electrodes was defined by
      their ability to entrain gastric slow waves and the induction of dysrhythmia.
      RESULTS: (1) The PETE recorded gastric slow waves comparable to the serosal
      electrodes. (2) Gastric electrical stimulation with long pulses delivered by the
      PETE, at a frequency of 10% higher than the intrinsic gastric slow wave
      frequency, entrained gastric slow waves. (3) Gastric electrical stimulation
      delivered by the PETE, at a tachygastric frequency, induced gastric dysrhythmia.
      LIMITATIONS: This was an animal study; however, its results are expected to be
      reproducible in humans, with PETE kept in place for even a longer duration than 6
      to 8 weeks. CONCLUSION: PETE placement is both feasible and safe. PETEs are
      effective, having a potential for use in treatment of both gastroparesis and
      obesity.

PMID- 18718586
TI  - Prospective assessment of EUS criteria for lymphadenopathy associated with rectal
      cancer.
AB  - BACKGROUND: There are few data that assess the accuracy of echo characteristics
      for predicting lymph-node (LN) metastases in patients with rectal cancer.
      OBJECTIVE: To identify nodal echo characteristics and size predictive of
      malignant infiltration and to determine if any combination of standard nodal
      criteria has sufficient predictive value to preclude FNA. DESIGN: Prospective
      uncontrolled study. SETTING: Tertiary-referral hospital. PATIENTS: Seventy-six
      patients (68% men) with untreated rectal cancer; 52 had visualized LNs.
      INTERVENTION: EUS-guided FNA. MAIN OUTCOME MEASUREMENTS: Evaluation of perirectal
      nodal morphology accuracy that corresponds to malignant cytology and
      identification of echo criteria, including LN size, to have sufficient predictive
      value to predict malignancy. RESULTS: Forty-three of 52 patients (83%) underwent
      FNA of a visualized LN. Nodal hypoechogenicity and short-axis length >or=5 mm
      were factors independently predictive of malignancy. The number of malignant
      nodal echo features per node did not distinguish benign from malignant pathology,
      except when all 4 features were present. Only 68% of malignant LN had >or=3 echo
      characteristics. An optimum LN short-axis or long-axis length cutoff value of 6
      mm or 9 mm were 90% and 95% specific, respectively, for the presence of
      malignancy by receiver operating characteristic analysis. LIMITATIONS: FNA was
      performed in a subset of identified LNs. CONCLUSIONS: Nodal echo features alone
      are often inadequate to establish the presence of locoregional metastatic disease
      by EUS. These data support the value of FNA to confirm the presence of malignancy
      in place of relying on imaging criteria.

PMID- 18718587
TI  - Effect of cervical mucus aspiration before intrauterine insemination.
AB  - OBJECTIVE: To determine whether cervical mucus aspiration before intrauterine
      insemination (IUI) has any effect on clinical pregnancy rates. METHOD: The
      outcomes of 186 IUI cycles in 95 consecutive patients in whom mucus was aspired
      prior to IUI were compared retrospectively with those of 1057 IUI cycles in 505
      women. RESULTS: The pregnancy rate was 15.1% (28 pregnancies for 186 cycles) in
      the cervical mucus aspiration group and 9.9% (105 pregnancies for 1057 cycles) in
      the control group (P=0.05). Mucus aspiration led to significantly increased
      pregnancy rates for women with unexplained infertility (24% in the aspiration
      group vs 9.5% in the control group; P=0.04). CONCLUSION: Cervical mucus
      aspiration before IUI might improve clinical pregnancy rates by yet-to-be-defined
      mechanisms.

PMID- 18718588
TI  - Postpartum carotid artery dissection.

PMID- 18718589
TI  - Pattern recognition using transabdominal ultrasound to diagnose ovarian mature
      cystic teratoma.
AB  - OBJECTIVE: To determine the validity of sonographic pattern recognition in the
      diagnosis of mature cystic teratoma. METHODS: Consecutive patients scheduled for
      elective surgery for adnexal masses were included in the study. All patients
      underwent transabdominal ultrasound with color extended-flow mapping within 24
      hours prior to surgery. Examinations were performed by the same sonographer to
      identify benign cystic teratoma. The final diagnoses were based on
      histopathologic findings. RESULTS: A total of 329 consecutive patients were
      recruited; 23 were excluded because the masses were not adnexal masses. Of the
      remaining 306 patients, 36 masses were found to be mature cystic teratomas and
      270 were nonteratomas. Sonographic pattern recognition showed a sensitivity of
      94.4% and a specificity of 98.2%. CONCLUSION: Sonographic pattern recognition
      using transabdominal ultrasound with color extended-flow mapping can accurately
      diagnose mature cystic teratoma.

PMID- 18718590
TI  - Episiotomy: what's the angle?

PMID- 18718591
TI  - Women's opinions and experiences with induction of labor and cesarean delivery on
      request in south eastern Nigeria.
AB  - OBJECTIVE: To assess the opinions and experiences of women regarding induction of
      labor and cesarean delivery on request in south eastern Nigeria. METHOD: Women
      were interviewed using questionnaires on their awareness of their right to
      request labor induction and/or a cesarean delivery, and of their experience and
      opinion of the procedures. RESULTS: Of the 15.1% of the respondents who knew they
      could request a cesarean delivery, 2.4% had requested one; and of the 56.3% who
      knew they could request labor induction, 6.9% had requested one. Only 5.3% and
      11.3% of the respondents who would chose the former or the latter procedure,
      respectively, said that they would insist on receiving it. Fear of their
      physicians' negative attitude regarding the procedures, and/or abandonment of
      care, ranked highest among their reasons for not insisting. CONCLUSION: In south
      eastern Nigeria few women are aware of their right to a cesarean delivery on
      request and the rate of refusal to perform such deliveries is high among
      physicians; more women are aware of their right to receive induction of labor on
      request and the acceptance rate is higher among physicians; and most women are
      unwilling to insist that their physician respect their choice.

PMID- 18718592
TI  - Manometric evaluation of anal sphincter function after vaginal and cesarean
      delivery.
AB  - OBJECTIVE: To compare anal sphincter function following spontaneous vaginal
      delivery and cesarean delivery, and assess the association of perineal length and
      sphincter injury with each delivery mode. METHOD: Perineal length was measured
      and anal manometric measurements were performed in 120 primigravidas before and
      after delivery. RESULTS: Mean values for maximum anal resting and squeeze
      pressures were significantly lower after delivery irrespective of the mode of
      delivery, but there was a positive correlation between postpartum maximum anal
      resting pressure and perineal length (r=0.24, P<0.01). CONCLUSION: Anal sphincter
      function was disturbed after both vaginal and cesarean delivery, a finding
      weakened by the fact that almost half of the cesareans were performed for
      cephalopelvic disproportion identified during labor.

PMID- 18718593
TI  - Update of Japanese common LDLR gene mutations and their phenotypes: Mild type
      mutation L547V might predominate in the Japanese population.
AB  - We investigated the LDLR gene mutations in 205 unrelated Japanese FH (familial
      hypercholesterolemia) heterozygotes to see if there is a prevalence of common
      mutations in the Japanese population. A total of 53 different small mutations
      (<25bp) and 10 kinds of large deletions (>25bp) were identified. Among them there
      were eight relatively frequent mutations: C317S, c.1845+2T>C, K790X, L547V,
      P664L, D412H, c.2312-3C>A and V776M. The patients with these mutations comprised
      32% of the total FH heterozygotes investigated. Comparison of clinical phenotypes
      of the eight frequent mutations disclosed that a missense mutation, L547V,
      manifested a milder phenotype than the other mutations. The mild clinical
      phenotype was shown to be based on the high level of receptor activity remaining
      on the patient's cell surfaces. When we examined the presence of common mutations
      in a general population, the L547V mutation was detected with unexpectedly higher
      frequency than the other mutations, suggesting an underestimation of the
      frequency of this mutation in FH heterozygote patients. In conclusion, although
      there is a broad spectrum of LDLR gene mutations in the Japanese population,
      eight common mutations were observed. Among them, a mild phenotype mutation,
      L547V, might predominate in the Japanese population.

PMID- 18718594
TI  - Using reverse engineering and computational fluid dynamics to investigate a lower
      arm amputee swimmer's performance.
AB  - In front crawl swimming, the hand and the corresponding forearm generate major
      propulsive forces. Such forces have been studied largely through experimental
      tests and more recently through the use of steady computational fluid dynamics
      (CFD). However, the effect of the upper arm on the propulsive forces has
      generally not been taken into consideration. An understanding of such forces is
      fundamental for the performance of swimmers who have an arm amputation at the
      level of the elbow. This study introduces the great potential offered by the
      multidisciplinary approach combining reverse engineering and unsteady CFD in a
      novel dynamic and interactive way. A complex CFD mesh model, representing the
      swimmer body and its upper arm, is produced. The model, including the arm
      rotation and a body roll movement, interacts dynamically with the fluid flow.
      Forces generated by the upper arm can then be investigated in great detail. In
      this particular study, it is found that the upper arm effectively contributes to
      the propulsion of the body. The propulsive force was numerically computed
      throughout the pull and reaches maxima of 8 N. Results obtained in this study
      could be extended in a similar way to any other limb movement within a fluid
      flow.

PMID- 18718595
TI  - Modeling balance control during sustained waking allows posturographic sleepiness
      testing.
AB  - We develop a method to quantify sleepiness. Sleepiness is a major risk factor in
      traffic and occupational accidents, but lack of convenient tests precludes
      monitoring impending sleepiness. Posturographic balance testing could address
      this need because sleepiness increases postural sway. It is, however, unclear how
      sleepiness influences balance control. Our results, for 12 subjects, show that
      balance control is more susceptible to increasing time awake (TA) compared to
      neuromuscular processes. This conclusion is reached since during sustained waking
      the control process slows down by 3.4% per hour of increased TA. This slowdown
      accounts for 65% of the variance in diurnal balance. We quantified balance
      control by modeling the body as an inverted pendulum and by expressing the
      control as the critical time interval for open-loop control (Deltat(c)) of the
      center-of-mass movements of this pendulum. To estimate the subjects' TA, we
      regressed the Deltat(c) scores recorded during sustained waking against
      increasing TA, and equated separate Deltat(c) test scores with the diurnal
      Deltat(c) scores. We estimated TA with 68% positive predictive value. The results
      encourage implementing balance modeling into a device that performs clinical or
      industrial balance testing because the model-based Deltat(c) score responded to
      increasing TA.

PMID- 18718596
TI  - Trunk muscle onset and cessation in golfers with and without low back pain.
AB  - The knowledge of the onset and cessation timing of the paraspinal muscles that
      surround the lumbar spine is an important area of research for the understanding
      of low back pain. This study examined the timing of the erector spinae and
      external oblique muscle activity in a group of golfers with and without low back
      pain. The study compared the results of surface electromyography measurements for
      two groups of golfers. Twelve male golfers who had reported a mild or greater
      level of pain in the lower back that was experienced while playing golf were
      examined. A further fifteen male golfers who had reported no history of lower
      back pain in the previous 12 months were recruited as controls. The results
      showed that the low-back-pain golfers switched on their erector spinae muscle
      significantly in advance of the start of the backswing. This finding was not
      evident in the group who did not have low back pain symptoms. Low-back-pain
      golfers, therefore, may use the erector spinae muscle as a primary spinal
      stabiliser instead of the stronger deeper muscles such as transversus abdominis
      and multifidus. These results may have important implications for conditioning
      programmes for golfers with low back pain.

PMID- 18718597
TI  - Effects of trochanteric soft tissue thickness and hip impact velocity on hip
      fracture in sideways fall through 3D finite element simulations.
AB  - A major worldwide health problem is hip fracture due to sideways fall among the
      elderly population. The effects of sideways fall on the hip are required to be
      investigated thoroughly. The objectives of this study are to evaluate the
      responses to trochanteric soft tissue thickness (T) variations and hip impact
      velocity (V) variations during sideways fall based on a previously developed CT
      scan derived 3D non-linear and non-homogeneous finite element model of pelvis
      femur-soft tissue complex with simplified biomechanical representation of the
      whole body. This study is also aimed at quantifying the effects [peak impact
      force (F(max)), time to F(max), acceleration and peak principal compressive
      strain (epsilon(max))] of these variations (T,V) on hip fracture. It was found
      that under constant impact energy, for 81% decrease in T (26-5mm), F(max) and
      epsilon(max) increased by 38% and 97%, respectively. Hence, decrease in T (as in
      slimmer persons) strongly correlated to risk for hip fracture (phi) and strain
      ratio (SR) by 0.972 and 0.988, respectively. Also under same T and body weight,
      for 75% decrease in V (4.79-1.2m/s), F(max) and epsilon(max) decreased by 70% and
      86%, respectively. Hence, increase in V (as in taller persons) strongly
      correlated to phi and SR by 0.995 and 0.984, respectively. For both variations in
      T and V, inter-trochanteric fracture situations were well demonstrated by phi as
      well as by SR and strain contours, similar to clinically observed fractures.
      These quantifications would be helpful for effective design of person-specific
      hip protective devices.

PMID- 18718598
TI  - Microcalorimetric study of adsorption of human monoclonal antibodies on cation
      exchange chromatographic materials.
AB  - Adsorption of two human monoclonal antibodies on two different strong cation
      exchange resins is studied by isothermal titration microcalorimetry and
      independent adsorption isotherm measurements. The pH value is varied between 4.5
      and 7.0, using different buffer systems, the temperature is always 25 degrees C.
      The adsorption isotherm data is fitted using two different Langmuir type models.
      Combining the calorimetric and the adsorption data, the specific enthalpy of
      adsorption of the protein Deltah(p)(ads) is determined. At pH values near 7.0,
      where the antibodies are only weakly charged, the adsorption is exothermal. At
      small loadings the absolute number of Deltah(p)(ads) is then large and almost
      constant but it significantly decreases at higher loadings. This shows that the
      arrangement of antibody molecules on the absorber material depends on the loading
      and is less favourable at higher loadings. Despite the high positive charge of
      the antibody at pH values of about 5 the value of Deltah(p)(ads) is almost zero
      along the entire isotherm. Furthermore, at pH 4.5 even endothermal effects are
      observed, although high binding capacities are found. At these conditions the
      adsorption process seems to be strongly influenced by the ions bound to the
      antibody. Their release upon absorption explains the endothermal caloric effect.
      The adsorption equilibrium constant K(eq) is calculated from the isotherms. From
      Deltag(p)(ads) and the calorimetric results for Deltah(p)(ads), Deltas(p)(ads),
      the entropy change upon adsorption of the protein is found for the different
      studied conditions.

PMID- 18718599
TI  - Hydrophobic interaction chromatography of proteins III. Transport and kinetic
      parameters in isocratic elution.
AB  - The effective pore diffusivities, D(e), of five model proteins (ribonuclease A,
      lysozyme, alpha-lactalbumin, ovalbumin, and BSA) in eight commercial phenyl
      hydrophobic interaction chromatography (HIC) media were determined by analyzing
      the plate height data from isocratic elution using the first two moments of the
      general linear rate model. The adsorbents represent a diverse set of HIC media
      that are widely used for protein purification. The estimated pore diffusivities
      were used to calculate the elution profiles of proteins in these adsorbents and
      were compared with the elution profiles obtained experimentally. High protein
      loading and sample protein concentration led to the underestimation of the pore
      diffusivity by the linear rate model. Comparisons between the calculated and the
      experimental profiles suggest that the pore diffusivities obtained from the
      linear rate model are generally accurate for proteins with low structural
      flexibility but not for more flexible ones, presumably because conformational
      change effects contribute significantly to the overall HETP. The general linear
      rate model was modified to account for the protein folding/unfolding kinetics,
      and parameter values could be estimated by fitting the experimental elution
      profiles to the modified model. In addition to conformational change, adsorbent
      type also had a significant effect on the accuracies of the pore diffusivities
      estimated by the linear rate model. The results also show that pore diffusion was
      the rate-limiting step in all absorbents for rigid proteins such as ribonuclease
      A and lysozyme. For structurally flexible proteins, conformational change
      contributed significantly to the overall reduced plate heights of the isocratic
      elution peaks. The physical properties of adsorbents, such as protein accessible
      porosity, pore size distribution, pore radius and pore connectivity, play
      important roles in determining the effective protein pore diffusivities.

PMID- 18718600
TI  - Solvent-resistant sol-gel polydimethyldiphenylsiloxane coating for on-line
      hyphenation of capillary microextraction with high-performance liquid
      chromatography.
AB  - A sol-gel polydimethyldiphenylsiloxane (PDMDPS) coating was developed for
      capillary microextraction on-line hyphenated with high-performance liquid
      chromatography (HPLC). This coating was created using methyltrimethoxysilane
      (MTMS) as the sol-gel precursor and di-hydroxy-terminated PDMDPS as the sol-gel
      active polymer. The methyl and phenyl groups on the sol-gel active polymer and
      the methyl groups on the sol-gel precursor ultimately turned into pendant groups
      providing the ability to extract non-polar analytes. A 40-cm segment of 0.25 mm
      I.D. fused silica capillary containing the sol-gel PDMDPS coating was installed
      as an external sampling loop in an HPLC injection port. Aqueous samples
      containing polycyclic aromatic hydrocarbons (PAHs), aromatic compounds, ketones,
      and aldehydes were passed through this capillary wherein the analytes were
      extracted by the sol-gel coating. The extracted analytes were then transferred to
      the HPLC column using isocratic or gradient elution with an acetonitrile/water
      mobile phase. This capillary demonstrated excellent extraction capability for non
      polar (e.g., polycyclic aromatic hydrocarbons and aromatic compounds) as well as
      moderately polar compounds, such as aromatic amines, ketones, and aldehydes. The
      test results indicate that PDMDPS can be successfully immobilized into a sol-gel
      network and that the resulting solvent-resistant sol-gel organic-inorganic hybrid
      coating can be effectively used for on-line hyphenation of capillary
      microextraction with high-performance liquid chromatography. The test results
      also indicate that the sol-gel PDMDPS coated capillary is resistant to high
      temperature solvents, making it suitable for applications in high-temperature
      HPLC. To the best of our knowledge, this is the first report on the creation of a
      silica-based sol-gel PDMDPS coating used in capillary microextraction on-line
      hyphenated to HPLC.

PMID- 18718601
TI  - Determination of nanoparticle diffusion coefficients by Taylor dispersion
      analysis using a capillary electrophoresis instrument.
AB  - The collective diffusion coefficient D(C) of diluted suspensions of positively
      charged iron oxide maghemite particles was experimentally investigated using a
      capillary electrophoresis instrument on the grounds of Taylor dispersion theory.
      Conditions for this approach to be applicable to nanoparticles of mean solid
      diameter below 10nm were set in this work, enabling precisions on D(C)
      determination of less than 2% relative standard deviation (RSD). Significantly
      different D(C) values were thus measured for particle populations differing in
      solid number mean diameter by only 2 nm. The obtained values were compared to the
      z-average diffusion coefficient derived from dynamic light scattering (DLS)
      experiments and used for the calculation of the Stokes radius. The measured
      diffusion coefficients appeared to be dependent on particle volume fraction and
      electrolyte ionic strength. These observations were eventually discussed in terms
      of particle interactions.

PMID- 18718602
TI  - A flow-cytometric method to investigate glutamate-receptor-sensitivity in whole
      blood platelets - results from healthy controls and patients with schizophrenia.
AB  - Hypofunction of glutamate receptors may contribute to the symptoms of
      schizophrenia. Human platelets express glutamate receptors and can serve as
      peripheral surrogate model for neuronal cells. Aim of this study was to establish
      a fast and sensitive flow-cytometric method to determine the glutamate-dependent
      kinetics of intracellular calcium ([Ca++]i) mobilization in platelets of
      schizophrenic patients. Glutamate stimulated [Ca++]i response was measured with a
      flow-cytometer in anti-CD-41a-labelled whole blood platelets of treated
      schizophrenic patients (n=18) and controls (n=18). In two control experiments the
      NMDA-receptor antagonist MK-801 and the dopamine antagonist amisulpride,
      respectively, were added to probes from healthy subjects. Stimulation with
      glutamate led dose-dependently to a mobilization of [Ca++]i in both healthy
      controls and patients. This effect was significantly reduced in patients. In
      vitro NMDA-antagonism inhibited the glutamate response, whereas dopamine
      antagonism had no effect. Our flow-cytometric method allows to measure glutamate
      receptor mediated [Ca++]i response in whole blood platelets, without requiring
      platelet rich preparations. The reduced glutamate-response in the patients was
      not explained by a direct inhibitory treatment effect. However, further studies
      with drug naive patients will be necessary to find out whether or not the
      observed hypoglutamergic function of platelets is endogenous to the disorder.

PMID- 18718603
TI  - Angiotensin-converting enzyme (ACE, I/D) gene polymorphism and susceptibility to
      abdominal aortic aneurysm or aortoiliac occlusive disease.
AB  - BACKGROUND: The purpose of this study was to examine the role of polymorphism in
      angiotensin converting enzyme gene (ACE, I/D) in the development of abdominal
      aortic aneurysm (AAA) or aortoiliac occlusive disease (AIOD). MATERIALS AND
      METHODS: We investigated 829 individuals in 4 groups: AAA (n = 133), AIOD (n =
      152), control (n = 152), and a random Polish population group (n = 392). ACE I/D
      gene polymorphism analysis was performed by polymerase chain reaction and gel
      electrophoresis. The genotype distribution was in Hardy-Weinberg equilibrium.
      RESULTS: The genotype distribution and allele frequency of ACE I/D were not
      significantly different between patients with AAA or AIOD and the control or the
      population group. Significant differences were found between the following
      groups: 1) hypertensive patients with AAA and normotensive patients with AAA (OR
      = 3.08 95% CI 1.22-7.79, P = 0.0147); 2) hypertensive patients with AAA and the
      population group (OR = 2.56; 95% CI 1.27-5.16, P = 0.0066). Since the majority of
      subjects were male, these associations were also true when only male hypertensive
      subjects with AAA were compared with male normotensive patients with AAA or to
      male population group. No relation of the ACE gene polymorphism to hypertension
      in the AIOD group was found. CONCLUSIONS: ACE I/D gene polymorphism is not a
      susceptibility factor to aortoiliac occlusive disease; however it may be an
      important factor in the development of AAA when coexisting with hypertension.

PMID- 18718604
TI  - The effects of riluzole on neurological, brain biochemical, and histological
      changes in early and late term of sepsis in rats.
AB  - OBJECTIVE: One of the underlying mechanisms of sepsis is thought to be the
      oxidative damage due to the generation of free radicals. Glutamate, the major
      excitatory amino acid in the brain, is known to play an important role in blood
      brain barrier (BBB) permeability, brain edema, and oxidative damage in
      pathological conditions. Riluzole, a glutamate release inhibitor, has been shown
      to have neuroprotective effects in several animal models. The aim of our study
      was to investigate the putative protective effect of riluzole against sepsis
      induced brain injury. METHODS: Sepsis was induced by cecal ligation and puncture
      in Wistar albino rats. Sham operated (control) and sepsis groups received either
      saline or riluzole (6 mg/kg, s.c.) 30 min after the surgical procedure, and every
      12 h as continuing treatment. The effect of riluzole on the survival rate, weight
      loss, fever, leukocyte count, brain edema, BBB permeability, oxidative damage,
      and histological observations were evaluated for early (6 h) and late (48 h)
      phase of sepsis. RESULTS: Riluzole, when administered 6 mg/kg s.c., diminishes
      the sepsis-induced augmentation in weight loss, body temperature, brain edema,
      increase in BBB permeability, oxidative damage, and brain injury that is observed
      histologically. Besides increasing the survival rate in sepsis, it has also
      improved neurological examination scores and the prognosis of the disease.
      CONCLUSION: According to the results of this study, riluzole appears to have a
      protective effect for sepsis-induced encephalopathy.

PMID- 18718605
TI  - Effects of admission glucose level on mortality after subarachnoid hemorrhage: a
      comparison between short-term and long-term mortality.
AB  - BACKGROUND: Admission hyperglycemia is associated with poor functional outcomes
      and risk of death in nondiabetic patients with acute ischemic stroke. However,
      there is still some debate about the effects of hyperglycemia in subarachnoid
      hemorrhage (SAH) patients. The purpose of this study was to assess whether the
      admission glucose level in patients with SAH is associated with short- and/or
      long-term mortality. METHODS: A consecutive data set of SAH patients without
      diabetes was obtained from a prospective multicenter cohort of hemorrhagic stroke
      patients. The effects of glucose level were examined in relation to short- (30
      days) or long-term mortality using Cox regression analysis. To eliminate the
      short-term effects of glucose level, the long-term effects were analyzed in the
      patients who survived for more than 30 days. RESULTS: A total of 803 SAH patients
      were followed up in this study. The 30-day and final mortalities were 7.6% and
      12.0%, respectively. Throughout the entire follow-up period, glucose level was
      found to be significantly associated with final mortality after adjusting for
      potential confounders (adjusted HR, 1.10; 95% CI, 1.01 to 1.19). Moreover,
      glucose level was found to be associated with short-term mortality (adjusted HR,
      1.15; 95% CI, 1.05 to 1.27), but not with long-term mortality (adjusted HR, 0.97;
      95% CI, 0.82 to 1.14). CONCLUSIONS: We demonstrated that admission hyperglycemia
      has a harmful effect on short-term mortality, but not with long-term mortality in
      SAH patients without diabetes. Our results may be used as further evidence to
      support a hypothesis of harmful effects of hyperglycemia in SAH patients.

PMID- 18718606
TI  - The two articles published in the Journal of Neurological Sciences by Dr. Oka.

PMID- 18718608
TI  - Re: Radical nephrectomy for pT1a renal masses may be associated with decreased
      overall survival compared with partial nephrectomy R. H. Thompson, S. A.
      Boorjian, C. M. Lohse, B. C. Leibovich, E. D. Kwon, J. C. Cheville and M. L.
      Blute J Urol 2008; 179: 468-473.

PMID- 18718609
TI  - WITHDRAWN

PMID- 18718610
TI  - Re: The incidence of fluoroquinolone resistant infections after prostate biopsy-
      are fluoroquinolones still effective prophylaxis? J. Feliciano, E. Teper, M.
      Ferrandino, R. J. Macchia, W. Blank, I. Grunberger and I. Colon J Urol 2008; 179:
      952-955.

PMID- 18718611
TI  - Re: How does the pre-massage and post-massage 2-glass test compare to the meares
      stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome?
      J. C. Nickel, D. Shoskes, Y. Wang, R. B. Alexander, J. E. Fowler, jr., S.
      Zeitlin, M. P. O'Leary,M. A. Pontari, A. J. Schaeffer, J. R. Landis, L. Nyberg,
      j. W. Kusek and K. J. Propert J Urol 2006; 176: 119-124.

PMID- 18718613
TI  - Re: Robotic simple prostatectomy R. Sotelo, R. Clavijo, O. Carmona, A. Garcia, E.
      Banda, M. Miranda and R. Fagin J Urol 2008; 179: 513-515.

PMID- 18718614
TI  - WITHDRAWN

PMID- 18718616
TI  - Re: Ureteral stenting and urinary stone management: a systematic review G.
      Haleblian, K. Kijvikai, J. de la Rosette and G. Preminger J Urol 2008; 179: 424
      430.

PMID- 18718617
TI  - Correlation of prenatal and postnatal ultrasound findings with the incidence of
      vesicoureteral reflux in children with fetal renal pelvic dilatation.
AB  - PURPOSE: Up to 1% of prenatal ultrasounds detect renal pelvic dilatation. This
      dilatation is associated with vesicoureteral reflux but its clinical significance
      and the necessity for vesicoureteral reflux detection have been questioned. We
      report an evaluation of fetal renal pelvic dilatation and postnatal sonographic
      features with the incidence of vesicoureteral reflux. MATERIALS AND METHODS:
      Maximum fetal renal pelvic dilatation was prospectively measured at a single
      center between 1990 and 2003. Dilatation 4 mm or greater at less than 33 weeks of
      gestation, or 7 mm or greater at more than 33 weeks was the threshold for
      inclusion in the study. Postnatal evaluation included ultrasound and voiding
      cystourethrogram. Postnatal data included vesicoureteral reflux incidence and
      grade, and caliceal and ureteral dilatation on ultrasound. RESULTS: Of 215
      neonates 46 (21%) had vesicoureteral reflux. Mean renal pelvic dilatation was
      14.4 mm in those with reflux, which was not statistically different than the mean
      of 11.8 mm in 169 with a normal voiding cystourethrogram. ROC analysis revealed
      that fetal renal pelvic dilatation was a poor discriminator of reflux. Reflux was
      identified in a significantly greater number of neonates with vs without
      postnatal calicectasis (20% vs 9%, p <0.05). When fetal renal pelvic dilatation
      was combined with postnatal calicectasis, only 5% of infants with dilatation less
      than 10 mm and isolated renal pelvic dilatation had reflux, whereas reflux was
      identified in 25% with fetal renal pelvic dilatation 10 mm or greater and
      calicectasis (p <0.02). CONCLUSIONS: The magnitude of fetal renal pelvic
      dilatation is not reliably predictive of reflux and this measure alone cannot be
      used to direct postnatal cystography. However, postnatal calicectasis appears to
      be an important predictor of vesicoureteral reflux in children with fetal renal
      pelvic dilatation. Expectant management can be considered in the subset of
      newborns with minimal dilatation (less than 10 mm) and absent calicectasis.

PMID- 18718618
TI  - Parent perspectives of health related quality of life in adolescents with chronic
      kidney disease due to underlying urological disorders: an assessment using the
      Child Health Questionnaire-Parent Form 50.
AB  - PURPOSE: Little is known about health related quality of life in adolescents with
      chronic kidney disease due to urological anomalies. We assessed generic health
      related quality of life in this population using a validated parent proxy
      instrument. MATERIALS AND METHODS: In this multicenter prospective cohort study
      the Child Health Questionnaire-Parent Form 50, a generic health related quality
      of life parent proxy instrument, was administered to 92 parents of adolescents 10
      to 18 years old with chronic kidney disease. Mean summary measure and scale
      scores in adolescents with urological anomalies were compared to scores in those
      with other causes of kidney disease and in a representative American population
      sample. RESULTS: The cohort included 35 adolescents with an underlying diagnosis
      of congenital urological anomaly and 57 with another cause of kidney disease.
      There were no significant differences in mean scale or summary measure scores
      between the 2 diagnostic groups. When compared to a representative population
      sample, adolescents with congenital urological anomalies scored significantly
      worse on the questionnaire physical summary measure (44.5, 95% CI 39.9-49.1 vs
      52.0, 95% CI 51.1-52.9, p = 0.002), and on the Child Health Questionnaire scales
      physical functioning, role physical, general health perceptions, family
      activities and parental emotional impact. CONCLUSIONS: As assessed by Child
      Health Questionnaire-Parent Form 50, parents reported that adolescents with
      chronic kidney disease due to urological disorders scored lower on the physical
      summary measure than a population based reference sample and they reported a
      negative effect on family activities and parental emotional well-being. These
      findings suggest that the Child Health Questionnaire-Parent Form 50 could provide
      a family based assessment of generic health related quality of life in
      adolescents with urological disorders.

PMID- 18718619
TI  - Antibacterial activity of halogenated sesquiterpenes from Malaysian Laurencia
      spp.
AB  - During our studies on Malaysian Laurencia species, brominated metabolites,
      tiomanene, acetylmajapolene B, and acetylmajapolene A were isolated from an
      unrecorded species collected at Pulau Tioman, Pahang along with known majapolene
      B and majapolene A. Acetylmajapolene A was a mixture of diastereomers as in the
      case of majapolene A. Tiomanene may be a plausible precursor for
      acetylmajapolenes B and A. In addition, three known halogenated sesquiterpenes
      and two known halogenated C(15) acetogenins were found from other two unrecorded
      species collected at Pulau Karah, Terengganu and Pulau Nyireh, Terengganu,
      respectively. Some of these halogenated metabolites showed moderate antibacterial
      activity against some marine bacteria.

PMID- 18718620
TI  - Burn injury: economic and social impact on a family.
AB  - OBJECTIVE: To assess the burden of burn injury in primary and secondary hospitals
      in Bangladesh, and how these costs are reflected as social and economic burdens
      in the community. STUDY DESIGN: Cross-sectional study. METHODS: A direct method
      was adopted to estimate the cost of burn injury, which involved interviewing
      patients or their attendants. Patient discharge records from 16 district
      hospitals and 45 Upazila (lower political units) health complexes were used as
      the main data sources in this study. Discharge records for December 2000 were
      reviewed for all types (injury and non-injury) of hospital admissions, and
      discharge records for January to December 2000 were reviewed for injury
      admissions. Hospital emergency departments' records for December 2000 were
      reviewed to study emergency injury cases. Patient interviews were conducted
      between February and March 2001 in selected primary and secondary hospitals in
      Bangladesh. RESULTS: Seven hundred and ninety-one burn patients were admitted in
      2000, which constituted 2% of total injury admissions. Hospital records of all
      types of admission in December 2000 revealed that burn patients represented 1% of
      the total admissions. The duration of hospital stay was significantly longer for
      patients with burn injury compared with patients with other injuries or
      illnesses. The longest hospital stay due to burn injury was 17.34 days, found for
      children aged 1-4 years. The average patient cost for burn injury was higher than
      that for other injuries and illnesses. CONCLUSION: Burn injuries were associated
      with a longer hospital stay compared with other injuries and illnesses. The
      management costs of burn injury, even using very incomplete data, were found to
      be very high in Bangladesh. To reduce this economic burden on families, an
      effective burn prevention programme should be developed.

PMID- 18718621
TI  - Predictors of antimalarial treatment failure in an area of unstable malaria
      transmission in eastern Sudan.
AB  - The factors that identify patients at risk of malaria treatment failure were
      evaluated in an area of unstable malaria transmission in eastern Sudan. We
      analyzed data from 471 patients who had been enrolled in six previous clinical
      antimalarial trials for uncomplicated Plasmodium falciparum malaria. Thirty-four
      (7.3%) had treatment failure (crude). In logistic regression models, an age of <
      or =5 years (odds ratio [OR]=3.7; 95% CI 1.5-8.6; P=0.002) and parasitaemia that
      took 3 days to clear (OR=2.4; 95% CI 1.0-5.9; P=0.04) were found to be predictors
      for treatment failure. Presenting temperature (OR=1.4; 95% CI 0.9-2.2; P=0.1),
      level of parasitaemia (OR=1.0; 95% CI 1.0-1.0; P=0.8) and presence of gametocytes
      (OR=0.3; 95% CI 0.9-1.2; P=0.1) were not associated with treatment failure. Thus,
      these factors might be used to identify those in whom treatment might fail in the
      future.

PMID- 18718622
TI  - Transcriptional control region rearrangements associated with the evolution of JC
      polyomavirus.
AB  - JC polyomavirus (JCV) isolates worldwide are classified into three super-lineages
      (A, B and C), with A and B further split into several lineages and sub-lineages.
      The transcriptional control region (TCR) of the JCV genome generally has the
      archetypal configuration, but rearranged TCRs have occasionally been detected in
      isolates from immunocompetent individuals. To investigate the phylogenetic
      significance of these rearrangements, we analyzed 298 TCR sequences all derived
      from complete JCV genomes directly cloned from the urine of non-immunocompromised
      individuals. While sporadic rearrangements were found in many lineages and sub
      lineages, common rearrangements were identified in all, or essentially all,
      isolates belonging to particular lineages or sub-lineages. Interestingly, several
      common rearrangements were also detected as sporadic rearrangements in other
      lineages or sub-lineages. This observation suggests that during the course of JCV
      evolution, JCV strains with sporadic rearrangements became predominant over
      archetypal TCRs in some JCV lineages or sub-lineages.

PMID- 18718624
TI  - Hydrogen production using single-chamber membrane-free microbial electrolysis
      cells.
AB  - Microbial electrohydrogenesis provides a new approach for hydrogen generation
      from renewable biomass. Membranes were used in all the reported microbial
      electrolysis cells (MECs) to separate the anode and cathode chambers. To reduce
      the potential losses associated with membrane and increase the energy recovery of
      this process, single-chamber membrane-free MECs were designed and used to
      investigate hydrogen production by one mixed culture and one pure culture:
      Shewanella oneidensis MR-1. At an applied voltage of 0.6 V, this system with a
      mixed culture achieved a hydrogen production rate of 0.53 m(3)/day/m(3) (0.11
      m(3)/day/m(2)) with a current density of 9.3A/m(2) at pH 7 and 0.69 m(3)/day/m(3)
      (0.15m(3)/day/m(2)) with a current density of 14 A/m(2) at pH 5.8. Stable
      hydrogen production from lactic acid by S. oneidensis was also observed. Methane
      was detected during the hydrogen production process with the mixed culture and
      negatively affected hydrogen production rate. However, by employing suitable
      approaches, such as exposure of cathodes to air, the hydrogenotrophic methanogens
      can be suppressed. The current density and volumetric hydrogen production rate of
      this system have potential to increase significantly by further reducing the
      electrode spacing and increasing the ratio of electrode surface area/cell volume.

PMID- 18718623
TI  - Direct association of the HPV16 E7 oncoprotein with cyclin A/CDK2 and cyclin
      E/CDK2 complexes.
AB  - The human papillomavirus (HPV) E7 oncoprotein has been shown to associate with
      cyclin/CDK2 complexes. Here we present evidence that HPV E7 proteins can
      associate with cyclin A/CDK2 and cyclin E/CDK2 complexes in cells that lack
      retinoblastoma tumor suppressor family members through sequences outside of the
      core retinoblastoma tumor suppressor binding site. Moreover, we show that HPV16
      E7 can directly associate with cyclin A/CDK2 and cyclin E/CDK2 complexes. These
      results suggest that cyclin/CDK2 complexes may be components of HPV E7-associated
      cellular complexes that do not contain retinoblastoma tumor suppressor family
      members.

PMID- 18718625
TI  - Inactivation of bacteria and viruses in human urine depending on temperature and
      dilution rate.
AB  - Source separation and reuse of human urine can decrease the environmental
      pollution of recipient waters and reduce the need for artificial mineral
      fertilisers. However, the reuse of urine introduces another pathogen transmission
      route that needs to be managed. The inactivation of enteric pathogens and model
      organisms (Salmonella enterica subspecies 1 serovar Typhimurium (S. typhimurium),
      Enterococcus faecalis, bacteriophages S. typhimurium 28B, MS2 and Phi x 174) by
      urine storage was studied at dilutions (urine:water) 1:0, 1:1 and 1:3 at
      temperatures 4, 14, 24 and 34 degrees C. A threshold concentration of ammonia was
      found at approximately 40 mM NH(3) (e.g. 2.1 g NH(3)-NL(-1) and pH 8.9 at 24
      degrees C), below which all studied organisms, except Salmonella, persisted
      considerably longer irrespective of treatment temperature, showing that urine
      dilution rate is of great importance for pathogen inactivation. For Salmonella
      spp. no threshold level was found in these studies (15 mM NH(3) lowest
      concentration studied). At temperatures below 20 degrees C, bacteriophage
      reduction was very slow. Therefore, urine stored at temperatures below 20 degrees
      C carries a high risk of containing viable viruses. The study indicated that the
      current recommended storage time for urine of 6 months at 20 degrees C or higher
      is safe for unrestricted use and could probably be shortened, especially for
      undiluted urine.

PMID- 18718626
TI  - Degradation of DBPs' precursors in river water before and after slow sand
      filtration by photo-Fenton process at pH 5 in a solar CPC reactor.
AB  - The generation of disinfection by-products during water treatment can be
      controlled by reducing the levels of precursor species prior to the chlorination
      step. The Natural Organic Matter (NOM) is the principal organic precursor and
      conventional removal of pollutants such as coagulation, flocculation and
      filtration do not guarantee the total NOM removal. In this study the degradation
      of NOM model compounds (dihydroxy-benzene) as well as the removal of NOM from
      river water via photo-Fenton process in a CPC solar photo-reactor is presented.
      The effect of solar activated photo-Fenton reagent at pH 5.0 before and after a
      slow sand filtration (SSF) in waters containing natural iron species is
      investigated and the details reported. The results showed that the total
      transformation of dihydroxy-benzene compounds along a mineralization higher than
      80% was obtained. The mineralization of the organic compounds dissolved in
      natural water was higher than in Milli-Q water, suggesting that the aqueous
      organic and inorganic components (metals, humic acids and photoactive species)
      positively affect the photocatalytic process. When 1.0mg/L of Fe(3+) is added to
      the system, the photo-Fenton degradation was improved. Therefore the photo-Fenton
      reagent could be an interesting complement to other processes for NOM removal.
      Comparing the response of two rivers as media for the organic compounds
      degradation it was observed that the NOM photo-degradation rate depends of the
      water composition.

PMID- 18718627
TI  - Potential for activated persulfate degradation of BTEX contamination.
AB  - The present study focused on evaluation of activated persulfate (PS) anion
      (S(2)O(8)(2-)) oxidative degradation of benzene, toluene, ethylbenzene, and
      xylene (constituents of gasoline and known collectively as BTEX) contamination.
      The results indicated that BTEX were effectively oxidized by PS in aqueous and
      soil slurry systems at 20 degrees C. PS can be activated thermally, or chemically
      activated with Fe(2+) to form the sulfate radical (SO(4)(-)) with a redox
      potential of 2.4V. The degradation rate constants of BTEX were found to increase
      with increased persulfate concentrations. For two PS/BTEX molar ratios of 20/1
      and 100/1 experiments, the observed aqueous phase BTEX degradation half-lives
      ranged from 3.0 to 23.1 days and 1.5 to 20.3 days in aqueous and soil slurry
      systems, respectively. In the interest of accelerating contaminant degradation,
      Fe(2+) and chelated Fe(2+) activated persulfate oxidations were investigated. For
      all iron activation experiments, BTEX and persulfate degradations appear to occur
      almost instantaneously and result in partial BTEX removals. It is speculated that
      the incomplete degradation reaction may be due to the cannibalization of SO(4)(-)
      in the presence of excess Fe(2+). Furthermore, the effects of various chelating
      agents including, hydroxylpropyl-beta-cyclodextrin (HPCD),
      ethylenediaminetetraacetic acid (EDTA), and citric acid (CA) on maintaining
      available Fe(2+) and activating PS for the degradation of benzene were studied.
      The results indicated that HPCD and EDTA may be less susceptible to chelated
      Fe(2+). In contrast, CA is a more suitable chelating agent in the iron activated
      persulfate system and with a PS/CA/Fe(2+)/B molar ratio of 20/5/5/1 benzene can
      be completely degraded within a 70-min period.

PMID- 18718628
TI  - Evaluation of chlorite and chlorate genotoxicity using plant bioassays and in
      vitro DNA damage tests.
AB  - In the last few years chlorine dioxide has been increasingly used for
      disinfecting drinking water in many countries. Although it does not react with
      humic substances, chlorine dioxide added to water is reduced primarily to
      chlorite and chlorate ions, compounds that are under investigation for their
      potential adverse effects on human health. The aim of this research was to study
      the genotoxicity of chlorite and chlorate and their mixtures. The end-points
      included two plant tests (chromosomal aberration test in Allium cepa and
      micronucleus assay in Tradescantia, carried out at different times of exposure)
      and two genotoxicity tests in human HepG2 cells (comet assay and cytokinesis
      blocked micronucleus test). Preliminary toxicity tests were carried out for both
      plant and HepG2 assays. The results showed that chlorite and chlorate are able to
      induce chromosomal damage to plant systems, particularly chromosomal aberrations
      in A. cepa root tip cells, even at concentrations lower than the limit
      established by Italian normative law and WHO guidelines. In HepG2 cells increased
      DNA damage was only observed for chlorate at the lowest concentration. No
      increase in micronuclei frequency was detected in any of the samples tested in
      human HepG2 cells.

PMID- 18718629
TI  - Sulfide-induced nitrate reduction in the sludge of an anaerobic digester of a
      zero-discharge recirculating mariculture system.
AB  - The anaerobic digester is a vital component in a zero-discharge mariculture
      system as therein most of the organic matter is mineralized and nitrogen
      containing compounds are converted to gaseous N(2). Although denitrification is a
      major respiratory process in this nitrate-rich treatment stage, also sulfate
      respiration takes place and may cause undesirable high sulfide concentrations in
      the effluent water. To examine the effect of sulfide on nitrate reduction, in
      situ depth profiles of inorganic nitrogen and sulfur compounds were determined.
      Additionally, nitrate reduction was examined as a function of ambient sulfide
      concentrations in sludge collected from different locations in the anaerobic
      reactor. Depth profiles showed high concentrations of nitrate and low
      concentrations of sulfide and ammonia in the aqueous layer of the reactor. A
      sharp decrease of nitrate and an increase in sulfide and ammonia concentrations
      was measured at the water-sludge interface. Nitrate reduction was highest in this
      interface zone with rates of up to 8.05+/-0.57 micromol NO(3)(-)h(-1)g((sludge))(
      1). Addition of sulfide increased the nitrate reduction rate at all sludge
      depths, pointing to the important role of autotrophic denitrification in the
      anaerobic reactor. Dissimilatory nitrate reduction to ammonia (DNRA) was found to
      be low in all sludge layers but was enhanced when sludge was incubated at high
      sulfide concentrations. Although nitrate reduction rates increased as a result of
      sulfide addition to sludge samples, no differences in nitrate reduction rates
      were observed between the samples incubated with different initial sulfide
      concentrations. This as opposed to sulfide oxidation rates, which followed
      Michaelis-Menten enzymatic kinetics. Partial oxidation of sulfide to elemental
      sulfur instead of a complete oxidation to sulfate, could explain the observed
      patterns of nitrate reduction and sulfide oxidation in sludge incubated with
      different initial sulfide concentrations.

PMID- 18718630
TI  - Fluidized bed reactor for the biological treatment of ion-exchange brine
      containing perchlorate and nitrate.
AB  - The removal of perchlorate and nitrate from contaminated drinking water using
      regenerable ion-exchange processes produces a high salt brine (3-10% NaCl) laden
      with high concentrations of perchlorate and nitrate. This bench-scale research
      describes the operation of acetate-fed granular activated carbon (GAC) based
      fluidized bed reactors (FBR) for perchlorate-only, and combined nitrate and
      perchlorate removal from synthetic brine (6% NaCl). The GAC was inoculated with a
      salt-tolerant culture developed by the authors and used previously in batch
      systems. An FBR was an effective design for perchlorate reduction and exhibited
      first-order degradation kinetics with respect to perchlorate concentrations.
      Nitrate was also removed by the organisms in the column and had no negative
      effects on the removal of perchlorate using the FBR design. However, at higher
      concentrations of nitrate the FBR was more difficult to operate due to loss of
      carbon and biomass from the formation of nitrogen bubbles and the high recycle
      flow rates needed.

PMID- 18718631
TI  - Congener-specific analysis of non-dioxin-like polychlorinated biphenyls in blood
      collected from 195 pregnant women in Sapporo City, Japan.
AB  - We conducted a congener-specific analysis of non-dioxin-like polychlorinated
      biphenyls (non-dioxin-like PCBs) in blood collected between July 2002 and July
      2004 from 195 pregnant women living in Sapporo City of Hokkaido Prefecture,
      Japan. The present study is one of the few studies in which full congener
      concentrations of non-dioxin-like PCBs have been measured in the blood of
      pregnant women. Of the 195 pregnant women, 101 were primipara (mean: 28.8 years,
      median: 28.0 years) and 94 were multipara (mean: 32.3 years, median: 33.0 years).
      Among the 197 non-dioxin-like PCB congeners, 58 congeners were identified in the
      blood of pregnant women. The arithmetic mean total concentrations of 58 non
      dioxin-like PCB congeners in the blood of primiparous and multiparous mothers in
      Sapporo City were 42.2-329.3 (mean: 114.5, median: 98.6) and 31.5-258.0 (mean:
      100.3, median: 91.4)ngg(-1)lipid, respectively. The results show that the
      contamination of non-dioxin-like PCBs in the blood of women has decreased
      compared to past levels in other domestic areas, in which the subject age was
      similar to that in this study. The results of the present study indicate that
      current levels of non-dioxin-like PCBs in the blood of Japanese women and can be
      used as baseline data for future temporal trends. The sums of the ratios of the
      concentrations of hexaCBs and heptaCBs to the total concentrations of 58 non
      dioxin-like PCB congeners in the blood of primiparous and multiparous mothers
      were 78.5% and 77.7%, respectively. The hexaCBs ratios in the blood of
      primiparous and multiparous mothers were 45.4% and 44.7%, respectively. HexaCB
      153 among hexaCBs congeners, the most abundant congener in the blood of
      primiparous and multiparous mothers, contributed approximately 22.0% and 21.8% to
      the total concentrations of 58 non-dioxin-like PCBs congeners that were measured
      in the blood, respectively. Among the non-dioxin-like PCB congeners measured in
      the present study, hexaCB-138, heptaCB-170, heptaCB-180, and heptaCB-182/heptaCB
      187 also showed high ratios to total concentrations of 58 non-dioxin-like PCB
      congeners detected in the blood of primiparous and multiparous mothers. With
      regard to the relationship between the total concentrations of 58 non-dioxin-like
      PCB congeners in maternal blood and the number of deliveries or the age of
      primiparous and multifarious mothers, the total levels of these PCB congeners
      tended to decreases with increases in the number of deliveries and significantly
      increased with increasing maternal age in both groups. Furthermore, significant
      correlations were observed between the total concentrations of these PCB
      congeners in blood and the age of primiparae and multiparae. The concentrations
      of hexaCB-153 in the blood of primiparous and multiparous mothers showed a close
      correlation to the total concentrations of these PCBs, suggesting that hexaCB-153
      could be an indicator of total concentrations of non-dioxin-like PCB congeners in
      the blood of pregnant women.

PMID- 18718632
TI  - Fourth WHO-coordinated survey of human milk for persistent organic pollutants
      (POPs): Belgian results.
AB  - Persistent organic pollutants (POPs) are chemicals that accumulate in the food
      chain and are toxic to humans and wildlife. The fourth World Health Organization
      (WHO) survey on POP levels in human milk (2006-2009) aims to provide baseline and
      trend information on human exposure to POPs. So far Belgium participated in all
      three previous rounds (1988, 1992, 2001). Whereas the first three rounds focused
      on determination of dioxins and PCBs in pooled (mixed) samples, the fourth survey
      comprised the analyses of individual milk samples for nine "basic POPs"
      (chlorinated pesticides and indicator PCBs) and of pooled milk samples for "basic
      POPs", "advanced POPs" (dioxins and dioxin-like PCBs) and "optional POPs"
      (polybrominated diphenylethers [PBDEs], polybrominated dioxins and dibenzofurans
      [PBrDD/F], mixed halogenated dioxins and dibenzofurans [PXDD/F] and
      hexabromocyclododecane [HBCD]). For the Belgian participation human milk samples
      were collected during the summer of 2006 from 197 women between 18 and 30 years
      old distributed over all Belgian provinces. The individual samples were analyzed
      in a Belgian Laboratory for "basic" POPs. A pooled sample was made from 178
      individual samples and analyzed by the WHO Reference Laboratory for the "basic,
      advanced and optional" POPs. The results indicate that most organochlorinated
      pesticides banned 25-30 years ago were below or around detection limits in
      Belgian human milk samples although DDE was still found at low levels in all
      samples. Over the last five years the levels of marker PCBs and PCDD/Fs in
      Belgian human milk decreased, respectively, by 58% and 39%. For some of the other
      emerging or older compounds recent international data are needed to allow
      comparison. This shows the importance of international studies as run by WHO.

PMID- 18718633
TI  - A comparison of sediment quality guidelines for toxicity assessment in the
      Sunderban wetlands (Bay of Bengal, India).
AB  - The aim of this paper was to obtain the first screening ecotoxicological risk
      evaluation in the Sunderban wetlands, the largest prograding delta in the
      estuarine phase of the River Ganges. The characterization of exposure was
      conducted by means of an extensive survey of several persistent organic
      pollutants (PAHs, PCBs, DDTs, PBDEs, HCHs, HCB) measured in seven core sediments
      from the Sunderban wetlands, obtaining a dataset with more than 2200 analyses.
      The pollutant effects were assessed by the use of three different sediment
      quality guidelines (SQGs) previously developed in the literature to evaluate
      toxicity induced in sediment-dwelling organisms. The three different approaches
      chosen for risk assessment of the Sunderban were the consensus SQGs obtained by
      TEC (threshold effect concentration), PEC (probable effect concentration) and EEC
      (extreme effect concentration), the threshold/probable effect level (TEL/PEL)
      approach and, finally, the ERL-ERM guidelines, including the m-ERM-Q (mean ERM
      quotient). The evaluation of the toxicity induced by a mixture of the target
      pollutants indicated the importance of gamma-HCH contamination in the Sunderban
      sediments despite the very low concentrations measured in core sediments. A
      different sensitivity for toxicity assessment due to quality guidelines was
      obtained, as the consensus SQGs based on TEC were less conservative and
      protective than the TEL and ERL approaches, while the use of m-ERM-Q seems to be
      the most powerful tool to predict the toxicity related to a contaminant mixture.

PMID- 18718634
TI  - Photo-electrochemical degradation of some chlorinated organic compounds on n-TiO2
      electrode.
AB  - The electrolysis of some chlorinated organic compounds such as chloroacetic
      acids, chloromethanes and chloroethenes were carried out on a photo-irradiated n
      TiO(2) electrode applied a constant potential, 1.0 V vs. Ag/AgCl, and the
      alternated pulse potentials of +1.0 V and various negative potentials, -1.0, -1.2
      and -1.4V vs. Ag/AgCl in 0.1 mol dm(-3) Na(2)SO(4) solutions saturated with
      oxygen or with nitrogen. These compounds were degraded on the n-TiO(2) electrode
      by the photo-electrolysis and mineralized to carbon dioxide, carbon monoxide and
      chloride ion. When the alternated pulse potentials were applied, the
      mineralization yields were increased for these compounds, especially for
      trichloroacetic acid and carbon tetrachloride, both of which were comparatively
      stable to the degradation in the constant potential electrolysis. The presence of
      oxygen in the solution was effective for the mineralization of these compounds,
      while little effective for that of trichloroacetic acid and of carbon
      tetrachloride.

PMID- 18718635
TI  - Monitoring of the total content of polycyclic aromatic hydrocarbons (PAHs) in
      arable soils in Poland.
AB  - The paper provides comprehensive information on the level of contamination of
      arable soils in Poland with polycyclic aromatic hydrocarbons (PAHs). Extensive
      monitoring studies were carried out to determine the content of the 16 priority
      PAHs in 216 soil samples collected in 2005 throughout arable lands (0-20 cm
      layer) in Poland. Locations of sampling points reflected the differences in
      regional industrialisation and urbanisation as well as in the characteristics of
      soils. The content of Sigma16PAHs ranged from 80 to 7264 microg kg(-1) with a
      median of 395 microg kg(-1) and with a dominance of 4-6 rings hydrocarbons (74%
      of total PAHs). Soil properties affected the PAHs content to a limited extend.
      The organic matter content was the only parameter correlated significantly
      (although weakly) with the concentrations of Sigma16PAHs; the strength of this
      relationship was more pronounced in soils with elevated OM content. The various
      molecular markers pointed to a prevailing pyrogenic origin of the PAHs in Polish
      arable soils, with minor contribution from liquid fuels combustion and traffic
      emissions. Two different Polish systems for classification of agricultural soils
      (providing for the content of Sigma9PAHs and Sigma13PAHs) indicate that the
      percentage of contaminated arable soils in Poland does not exceed 10%.
      Multivariate methods enabled an evaluation of spatial trends in Sigma16PAHs
      concentrations, an identification of regions with very low PAHs content (East
      part of the country), and a recognition of small industrial/urbanised areas of
      higher risk.

PMID- 18718636
TI  - Adsorption and transport of arsenate in carbonate-rich soils: coupled effects of
      nonlinear and rate-limited sorption.
AB  - The transport and fate of arsenate in carbonate-rich soil under alkaline
      conditions was investigated with multiple approaches combining batch, sequential
      extraction and column experiments as well as transport modeling studies. Batch
      experiments indicated that sorption isotherm was nonlinear over a wide range of
      concentration (0.1-200 mg L(-1)) examined. As(V) adsorption to the calcareous
      soil was initially fast but then continued at a slower rate, indicating the
      potential effect of rate-limited sorption on transport. Column experiments
      illustrated that transport of As(V) was significantly retarded compared to a non
      reactive tracer. The degree of retardation decreased with increasing As(V)
      concentration. As(V) breakthrough curves exhibited nonideal transport behavior
      due to the coupled effects of nonlinear and rate-limited sorption on arsenate
      transport, which is consistent with the results of modeling studies. The
      contribution of nonlinear sorption to the arsenate retardation was negligible at
      low concentration but increased with increasing As(V) concentration. Sequential
      extraction results showed that nonspecifically sorbed (easily exchangeable, outer
      sphere complexes) fraction of arsenate is dominant with respect to the inner
      sphere surface bound complexes of arsenate in the carbonate soil fraction,
      indicating high bioavailability and transport for arsenate in the carbonate-rich
      soils of which Fe and Al oxyhydroxide fractions are limited.

PMID- 18718637
TI  - Electrogenerative gold recovery from cyanide solutions using a flow-through cell
      with activated reticulated vitreous carbon.
AB  - An electrogenerative flow-through reactor with an activated reticulated vitreous
      carbon cathode was developed. The influence of palladium-tin activation of the
      cathode towards gold deposition was studied by cyclic voltammetry. The reactor
      proved to be efficient in recovering more than 99% of gold within 4 h of
      operation. The performance of the reactor was evaluated with initial gold
      concentrations of 10, 100 and 500 mg L-1 and various electrolyte flow rates. Gold
      recovery was found to be strongly dependent on electrolyte flow rate and initial
      gold concentration in the cyanide solution under the experimental conditions
      used.

PMID- 18718638
TI  - Stable lead isotopes in environmental health with emphasis on human
      investigations.
AB  - There has been widespread use of stable lead isotopes in the earth sciences for
      more than 40 years focussed on the origin and age of rocks and minerals with
      lesser application in environmental investigations where the emphasis has been
      directed typically to the source of lead in environmental media such as air,
      water and soils. In contrast, the number of environmental health investigations
      focussed on humans (and primates) is limited in spite of the demonstrated utility
      of the approach in pioneering studies in the early 1970's. This paper reviews the
      status of lead isotopes in human investigations especially over the past 2
      decades, the period over which most activity has taken place. Following a brief
      introduction to the method, examples are provided illustrating the use of lead
      isotopes in a wide spectrum of activities including sources and pathways of lead
      in diverse environments from urban to mining communities, various applications
      associated with pregnancy, the contribution of bone lead to blood lead including
      in the elderly, the half-life of lead in blood, and lead in bones and other
      media. A brief outline of critical research on non-human primates is also given.
      The lead isotope method is a powerful technique for tracing lead and could be
      employed more widely in human investigations.

PMID- 18718639
TI  - Structure and activity of plasmin and other direct thrombolytic agents.
AB  - The physiological or pharmacological dissolution of thrombi is ultimately
      accomplished by the serine protease plasmin. Plasmin is derived from its
      precursor plasminogen in a reaction catalyzed by plasminogen activators (PAs)
      such as tissue-type plasminogen activator (tPA). In the middle of the last
      century, plasmin was investigated as a potential thrombolytic agent. However,
      technical obstacles led to the abandonment of this agent, and by the 1970s PAs
      had become the standard of care for pharmacological management of various
      thrombotic conditions. Talecris Biotherapeutics has developed a methodology to
      prepare the plasmin product (Human) TAL-05-00018 that is rendered inactive by low
      pH (pH 3.0-4.0) until it is delivered directly to the neutral environment of a
      thrombus by catheter-assisted administration. TAL-05-00018 undergoes a rigorous
      manufacturing process to ensure a final product free from unactivated
      plasminogen, streptokinase, enveloped and non-enveloped viruses and prion
      proteins; generating an extremely high-purity product with a shelf life of three
      years at ambient temperature. TAL-05-00018 has shown promise in in vitro and pre
      clinical studies, and in early clinical trials, demonstrating a dose-dependant
      reduction in clot weight that compares favorably to that seen with tPA. Several
      other direct thrombolytics have also been developed, including the recombinant,
      modified deletion mutant of plasmin TAL6003 (Talecris Biotherapeutics), which
      retains all the major functional attributes of full-length plasmin.

PMID- 18718640
TI  - Is there a role for magnetic resonance imaging in diagnosing colovesical
      fistulas?
AB  - OBJECTIVES: Colovesical fistula is a devastating complication, usually secondary
      to diverticulitis or colon cancer. Imaging plays a crucial role in delineating
      the underlying anatomy and identifying an etiologic factor. Barium enema,
      computed tomography, and cystoscopy have been the mainstays of investigation, but
      they have less than ideal sensitivity and specificity. This study assessed the
      role of magnetic resonance imaging (MRI) in the investigation of patients with
      probable colovesical fistulas. METHODS: A total of 22 patients with presentations
      suspicious for enterovesical fistulas who underwent evaluation with axial T(1)
      weighted and axial, coronal, and sagittal T(2)-weighted 1.5T MRI (body-phased
      array) were identified. Of the 22 patients, 19 underwent laparotomy and repair.
      RESULTS: MRI correctly identified the presence of a fistula and defined the
      underlying etiology in 18 of 19 patients. Colovesical fistula was correctly
      excluded in 1 of 19 patients. The remaining 3 patients were either unfit for
      surgery or refused. CONCLUSIONS: The results of our study have shown that MRI is
      an accurate method of evaluating patients with suspicion of colovesical fistulas,
      identifying the anatomy of the tract, as well as the etiology. This is not only
      useful for diagnosis, but also for surgical planning.

PMID- 18718641
TI  - Effect of dutasteride on intraprostatic androgen levels in men with benign
      prostatic hyperplasia or prostate cancer.
AB  - OBJECTIVES: Dutasteride exerts its beneficial effects on the prostate through
      suppression of intraprostatic dihydrotestosterone (DHT). The aim of this analysis
      was to assess the effects of the approved dose of dutasteride (0.5 mg/d), given
      for 2 weeks to 4 months, on the serum and intraprostatic DHT and testosterone
      levels in 3 randomized studies. METHODS: Intraprostatic androgen levels were
      measured in benign prostatic tissue collected during transurethral resection of
      the prostate (benign prostatic hyperplasia studies, n = 256) or radical
      prostatectomy (prostate cancer study, n = 51), performed after 2 weeks, or 1, 3,
      or 4 months of treatment with dutasteride or with placebo or surgery alone. The
      serum androgen levels were assessed at the same points during treatment. Data
      from the control groups were pooled to provide 1 comparison group. RESULTS:
      Dutasteride reduced the intraprostatic DHT levels by 83%, 90%, 92%, and 93% after
      2 weeks and 1, 3, and 4 months of treatment, respectively, compared with
      placebo/surgery alone. Dutasteride reduced the serum DHT levels from baseline by
      84% at 2 weeks and by approximately 90% at 1, 2, 3, and 4 months compared with a
      5.2% increase in the control group. The decrease in DHT levels with dutasteride
      was accompanied by a reciprocal increase in the serum and intraprostatic
      testosterone levels. However, the intraprostatic testosterone levels in the
      dutasteride groups generally remained lower than the intraprostatic DHT levels in
      the control group. CONCLUSIONS: The results of our study have shown that
      dutasteride provides near-maximal suppression of both serum and intraprostatic
      DHT levels in men with benign prostatic hyperplasia or prostate cancer at all
      points assessed.

PMID- 18718642
TI  - Kidney cancer in American Indian and native Alaskan men and women-time to notice,
      time to care.

PMID- 18718643
TI  - TURP in patients with biopsy-proven prostate cancer: sensitivity for cancer
      detection.
AB  - OBJECTIVES: Recent laser techniques for the treatment of benign prostatic
      obstruction result in a significant amount of vaporization. Therefore, less
      tissue is retrieved for histologic evaluation. This might be an argument in favor
      of monopolar transurethral resection of the prostate (TURP). The aim of this
      retrospective study was to determine the ability to detect prostate cancer (PCa)
      in the TURP specimen of patients with biopsy-proven PCa and to gain information
      about the value of the TURP specimen during benign prostatic obstruction
      treatment. METHODS: The charts of 154 patients with biopsy-proven PCa who had
      undergone standard TURP before high-intensity focused ultrasound therapy were
      retrospectively reviewed. The pre- and postoperative characteristics and
      histologic features were analyzed to identify the sensitivity of TURP in terms of
      PCa detection. Patients with incidentally detected PCa or a history of
      radiotherapy or chemotherapy were excluded. All patients underwent TURP by an
      experienced surgeon (>1000 procedures). The histologic features were evaluated
      and the chips completely analyzed for PCa detection. The Mann-Whitney U test and
      chi(2) test were used for statistical analysis. RESULTS: Of the 154 patients, 84
      fulfilled the inclusion criteria. The mean patient age was 69.8 years (range 59
      82). The mean prostate-specific antigen level was 9.8 ng/dL, the mean prostate
      volume was 31.7 cm(3), and the average amount of resected tissue was 17.9 g. PCa
      was detected in 45 of 84 patients (54%). No significant differences between the
      group with histologic findings positive for PCa and the group with negative
      findings could be found in any of the recorded parameters. CONCLUSIONS: Only 54%
      of the PCa cases were detected by TURP. Therefore, the worth of the obtained
      tissue sample during TURP seems questionable.

PMID- 18718644
TI  - Calcifying nanoparticles (nanobacteria): an additional potential factor for
      urolithiasis in space flight crews.
AB  - Spaceflight-induced microgravity appears to be a risk factor for the development
      of urinary calculi, resulting in urolithiasis during and after spaceflight.
      Calcifying nanoparticles, or nanobacteria, multiply more rapidly in simulated
      microgravity and create external shells of calcium phosphate. The question arises
      whether calcifying nanoparticles are nidi for calculi and contribute to the
      development of clinically significant urolithiasis in those who are predisposed
      to the development of urinary calculi because of intrinsic or extrinsic factors.
      This case report describes a calculus recovered after flight from an astronaut
      that, on morphologic and immunochemical analysis (including specific monoclonal
      antibody staining), demonstrated characteristics of calcifying nanoparticles.

PMID- 18718645
TI  - Impact of body mass index on cost and clinical outcomes after percutaneous
      nephrostolithotomy.
AB  - OBJECTIVES: To evaluate the impact of body mass index (BMI) on clinical outcomes
      and costs associated with percutaneous nephrostolithotomy (PCNL). METHODS: We
      reviewed charts of 200 consecutive patients who underwent PCNL between September
      2005 and May 2007. We recorded patient and stone characteristics and
      perioperative outcomes. BMI was available for 150 patients (75%), who comprised
      our study group. We obtained direct and subcomponent costs (room and board,
      laboratory, pharmacy, radiology, operating room, surgical supplies, anesthesia,
      and recovery room). We divided patients into four BMI categories: normal weight
      (BMI < 25), overweight (25 <or= BMI < 30), obese (30 <or= BMI < 40), and morbidly
      obese (BMI >or= 40). We compared groups with regard to baseline characteristics,
      intraoperative parameters, stone-free and complication rates, and hospital length
      of stay. RESULTS: Mean stone size and proportion of patients with staghorn,
      multiple, and bilateral calculi were similar among groups. The normal weight
      cohort had proportionately fewer recurrent stone formers and patients with a
      history of stone surgery, compared with the other groups (P = .005 and P = .03,
      respectively). We found no significant differences among groups with regard to
      stone-free and complication rates, operative time, length of stay, or need for
      multiple accesses. Median direct cost was marginally, but not significantly,
      higher in normal weight ($8124) compared with overweight ($6746), obese ($6740),
      and morbidly obese ($6719) patients (P = .75). CONCLUSIONS: Body mass index had
      no impact on efficacy or complication rates of PCNL. Despite greater perceived
      difficulty in performing these procedures in overweight and obese patients, it
      was not more costly.

PMID- 18718646
TI  - Two girls with urethral duplication.
AB  - We present 2 cases of urethral duplication in girls, which has rarely been
      reported. Neither patient had any associated abnormalities. After a review of
      their clinical treatment and the current data on female urethral duplication, we
      recommend excision of the duplicated urethra and encourage diligent investigation
      in girls with complete incontinence, perineal discharge, or perineal or
      suprapubic sinuses, because urethral duplication might be underdiagnosed. A
      thorough examination is required, because most cases of duplication can be
      identified with careful inspection.

PMID- 18718647
TI  - Paraneoplastic leukemoid reaction as marker for transitional cell carcinoma
      recurrence.
AB  - A case of a 78-year-old man with transitional cell carcinoma and a paraneoplastic
      leukemoid reaction. The leukocytosis was present at the diagnosis of carcinoma.
      It dissipated with complete tumor resection, was absent when a surveillance
      computed tomography scan showed no evidence of recurrence at 6 months, and had
      returned with tumor recurrence at 8 months. This case demonstrates that a
      paraneoplastic leukemoid reaction can be used as a tumor marker in cases of
      transitional cell carcinoma when a leukemoid reaction is found at presentation.

PMID- 18718648
TI  - Risk factors for a serous cancer precursor ("p53 signature") in women with
      inherited BRCA mutations.
AB  - OBJECTIVES: Pelvic (ovarian) serous carcinomas frequently contain p53 mutations.
      Recently, a candidate serous cancer precursor (the p53 signature) with p53
      mutations and other features in common with serous cancer has been discovered in
      distal fallopian tube mucosa. This study examined the relationship of putative
      ovarian cancer risk factors with the presence of p53 signatures in women with
      BRCA mutations (BRCA+). METHODS: Fallopian tubes from 75 BRCA+ women were
      immunostained for p53 signatures and correlated with age at first childbirth,
      parity, oral contraceptive use, body mass index (BMI), and BRCA subtype (1 or 2).
      Statistical analysis was performed with the T-test or Chi-square analysis and
      logistic regression adjusting for age and parity. RESULTS: Thirty-eight percent
      of the tubes contained p53 signatures, which were significantly associated with
      older age at first childbirth (mean 30.8 vs. 28.4 years; p=0.04) and lower parity
      (mean 1.4 vs. 2.2; p=0.01) in univariate analyses. The unadjusted odds ratios
      were 3.8 (p-trend=0.04) for first childbirth>/=30 years versus <30 and 0.2 (p
      trend=0.01) for parity >/= 3 versus nulliparous women. After adjusting for age
      and parity, the trend for age at first childbirth became non-significant
      (adjusted odds ratio 3.5; p-trend=0.15), while that for parity remained
      significant (adjusted odds ratio 0.2; p-trend 0.02). CONCLUSIONS: The p53
      signature is significantly associated with lower parity and possibly higher age
      at first childbirth, further linking this entity to serous cancer via risk
      factors associated with ovulation. The p53 signature merits consideration as a
      surrogate marker for serous cancer risk.

PMID- 18718649
TI  - Prognostic role of the recepteur d'origine nantais (RON) expression in ovarian
      cancer patients.
AB  - OBJECTIVE: The aim of the study was to investigate the potential clinical
      relevance of immunohistochemically assessed RON expression in a large, single
      institution series of primary untreated advanced ovarian cancer patients.
      METHODS: Immunohistochemical analysis was performed by using the polyclonal
      rabbit anti-RON-beta antibody (C-20, clone sc-322, Santa Cruz, California).
      Results were expressed as the total proportion of immunostained tumor cells (RON
      positivity), or the percentage of cells showing strong staining of RON expression
      (H-RON positivity). RESULTS: In the overall series RON positive immunoreaction
      was observed in 103/141 cases, while H-Ron positivity was detected in 577141
      (40.4%) cases. No association between RON and H-RON expression with response to
      first-line treatment was documented. During the follow up period, progression and
      death of disease were observed in 111 (78.7%) and 76 (53.9%) cases, respectively.
      Cases with strong H-RON expression has a shorter overall survival (median=35
      months) than cases with low RON levels (median=59 months) (X(2)=-2.1, p
      value=0.032). In multivariate analysis, only platinum resistance, and extent of
      residual tumor retained an independent negative prognostic role for OS, with the
      percentages of H-RON positively immunostained cells showing a borderline
      statistical significance (p value=0.0643). The unfavourable role of elevated
      percentages of H-RON expression was maintained only in the subgroup of platinum
      resistant recurrent ovarian cancer patients (X(2)=3.89, p value=0.048) compared
      to the platinum sensitive ones (X(2)=1.98, p value=0.16). CONCLUSIONS: The
      assessment of RON expression deserves further attention as a parameter helpful to
      identify poor prognosis ovarian cancer patients potentially candidates to
      investigational agents.

PMID- 18718650
TI  - Simultaneous presentation of 2 rare hereditary immunodeficiencies: IL-12 receptor
      beta1 deficiency and ataxia-telangiectasia.

PMID- 18718651
TI  - Cord blood allergen-specific IgE is associated with reduced IFN-gamma production
      by cord blood cells: the Protection against Allergy-Study in Rural Environments
      (PASTURE) Study.
AB  - BACKGROUND: It is currently discussed whether allergic sensitization may start in
      utero under the influence of the maternal immune system and environmental
      determinants. OBJECTIVE: To investigate the relationship between allergen
      specific cord blood (CB) IgE levels, parental sensitization, CB cytokine
      production, and environmental influences. METHODS: As part of an ongoing
      multicenter birth cohort study, allergen-specific IgE antibodies against 20
      common seasonal, perennial, and food allergens were measured in blood samples
      from 922 neonates, 922 mothers, and 835 fathers. Supernatants from stimulated CB
      cells were assessed for the production of IL-5, IFN-gamma, IL-10, and TNF-alpha.
      RESULTS: Allergen-specific IgE antibodies were detectable in 23.9% of newborns.
      Contamination with maternal serum was excluded by several means of analyses,
      including the absence of IgA antibodies. Clear correlation between maternal and
      fetal IgE was found only for hen's egg, cow's milk, and soybean allergen. Fetal
      IgE correlated negatively with the level of IFN-gamma production, but not with IL
      5 and IL-10. CONCLUSION: Allergen-specific IgE antibodies most probably of fetal
      origin are detectable in CB and correlate with a lowered CB IFN-gamma production.

PMID- 18718652
TI  - Correlation between polymerization shrinkage and marginal fit of temporary
      crowns.
AB  - OBJECTIVES: During polymerization, temporary c&b materials (t-c&b) undergo
      shrinkage which may lead to marginal inaccuracies of the temporary restoration.
      The degree of correlation between these two factors is still unknown. Hence, the
      objective of this study was to determine the polymerization shrinkage of t-c&bs
      and to evaluate, to which degree the shrinkage is correlated to the width of the
      marginal gap. METHODS: Six different t-c&bs (2 monomethacrylates and 4
      dimethacrylates) were used to fabricate temporary crowns (n = 12) on two prepared
      teeth (stainless steel) of different diameters (5 and 7 mm). The crown diameters
      and marginal discrepancy were measured at various storage times after mixing (10,
      30, 60 min) using a travelling microscope. In addition, the shrinkage (bonded
      disk method) and content of inorganic filler (ashing method) were recorded. The
      statistical analysis was carried out using parametric tests, the F-test and
      Pearson's correlation (p = 0.05). RESULTS: The marginal discrepancies increased
      as a function of increasing storage time (10 min: 0.162-0.218 mm; 60 min: 0.271
      0.521 mm). Lower values were recorded for monomethacrylates than for the
      dimethacrylates (greatest changes recorded during the first 30 min). The
      shrinkage values recorded 10 min after mixing varied between 3.25 and 4.10%.
      There was no significant relationship between the width of the marginal gap and
      shrinkage (p > 0.05). SIGNIFICANCE: Shrinkage values are not suitable to predict
      the marginal accuracy of a temporary restoration. At least 30 min should elapse
      between fabricating and trimming temporary crowns to avoid further inaccuracies.

PMID- 18718653
TI  - The effect of a ceramic coating on the cpTi-porcelain bond strength.
AB  - OBJECTIVES: To investigate the bond strength between cpTi and low fusing
      porcelains after different treatments. METHODS: 72 patterns were covered with a
      ceramic coating and invested with phosphate-bonded material (group A), another 72
      were invested with magnesia material (group B) and all cast with cpTi. 31 solid
      castings were selected from each group. The castings of group B were ground and
      sandblasted, while the castings of group A were only sandblasted. Aluminum
      content of the metal surface was determined by EDS and castings were submitted to
      a 3-point bending test to determine the modulus of elasticity (E). The porcelains
      Duceratin Plus, Noritake Ti22 and Triceram were applied respectively and
      specimens were submitted to a 3-point bending test. The fracture mode and the
      remaining porcelain were determined by optical microscopy and SEM/EDS. Bond
      strength and fracture mode were calculated by two-way ANOVA. RESULTS: The E of
      groups A and B was 98.3 GPa and 98.6 GPa respectively. The bond strength was 26+/
      3 MPa (Duceratin Plus), 28+/-3 MPa (Noritake Ti22), 27+/-2 MPa (Triceram) for
      group A and 24+/-1 MPa, 29+/-2 MPa, 27+/-1 MPa for group B respectively. No
      significant differences were found for the same porcelain between the two groups
      (p<0.05). A significant difference was found between Duceratin Plus and Noritake
      Ti22, for group B (p<0.05). The mode of failure was mainly adhesive for all
      specimens. A significant reduction in aluminum was recorded in all subgroups.
      SIGNIFICANCE: The special coating of patterns makes the Ti casting procedure
      inexpensive, without reducing the metal-ceramic bond strength.

PMID- 18718654
TI  - Evaluation of interface characterization and adhesion of glass ceramics to
      commercially pure titanium and gold alloy after thermal- and mechanical-loading.
AB  - OBJECTIVES: This study evaluated the effect of thermal- and mechanical-cycling on
      the shear bond strength of three low-fusing glassy matrix dental ceramics to
      commercial pure titanium (cpTi) when compared to conventional feldspathic ceramic
      fused to gold alloy. METHODS: Metallic frameworks (diameter: 5 mm, thickness: 4
      mm) (N=96, n=12 per group) were cast in cpTi and gold alloy, airborne particle
      abraded with 150 microm aluminum oxide. Low-fusing glassy matrix ceramics and a
      conventional feldspathic ceramic were fired onto the alloys (thickness: 4 mm).
      Four experimental groups were formed; Gr1 (control group): Vita Omega 900-Au-Pd
      alloy; Gr2: Triceram-cpTi; Gr3: Super Porcelain Ti-22-cpTi and G4: Vita
      Titankeramik-cpTi. While half of the specimens from each ceramic-metal
      combination were randomly tested without aging (water storage at 37 degrees C for
      24 h only), the other half were first thermocycled (6000 cycles, between 5 and 55
      degrees C, dwell time: 13 s) and then mechanically loaded (20,000 cycles under 50
      N load, immersion in distilled water at 37 degrees C). The ceramic-alloy
      interfaces were loaded under shear in a universal test machine (crosshead speed:
      0.5 mm/min) until failure occurred. Failure types were noted and the interfaces
      of the representative fractured specimens from each group were examined with
      stereomicroscope and scanning electron microscope (SEM). In an additional study
      (N=16, n=2 per group), energy dispersive X-ray spectroscopy (EDS) analysis was
      performed from ceramic-alloy interfaces. Data were analyzed using ANOVA and
      Tukey's test. RESULTS: Both ceramic-metal combinations (p<0.001) and aging
      conditions (p<0.001) significantly affected the mean bond strength values.
      Thermal- and mechanical-cycling decreased the bond strength (MPa) results
      significantly for Gr3 (33.4+/-4.2) and Gr4 (32.1+/-4.8) when compared to the non
      aged groups (42.9+/-8.9, 42.4+/-5.2, respectively). Gr1 was not affected
      significantly from aging conditions (61.3+/-8.4 for control, 60.7+/-13.7 after
      aging) (p>0.05). Stereomicroscope images showed exclusively adhesive failure
      types at the opaque ceramic-cpTi interfacial zone with no presence of ceramic on
      the substrate surface but with a visible dark titanium oxide layer in Groups 2-4
      except Gr1 where remnants of bonder ceramic was visible. EDS analysis from the
      interfacial zone for cpTi-ceramic groups showed predominantly 34.5-85.1% O(2)
      followed by 1.1-36.7% Al and 0-36.3% Si except for Super Porcelain Ti-22 where a
      small quantity of Ba (1.4-8.3%), S (0.7%) and Sn (35.3%) was found. In the Au-Pd
      alloy-ceramic interface, 56.4-69.9% O(2) followed by 15.6-26.2% Si, 3.9-10.9% K,
      2.8-6% Na, 4.4-9.6% Al and 0-0.04% Mg was observed. SIGNIFICANCE: After thermal
      cycling for 6000 times and mechanical-cycling for 20,000 times, Triceram-cpTi
      combination presented the least decrease among other ceramic-alloy combinations
      when compared to the mean bond strength results with Au-Pd alloy-Vita Omega 900
      combination.

PMID- 18718655
TI  - The effect of devitalized trabecular bone on the formation of osteochondral
      tissue-engineered constructs.
AB  - In the current study, evidence is presented demonstrating that devitalized
      trabecular bone has an inhibitory effect on in vitro chondral tissue development
      when used as a base material for the tissue-engineering of osteochondral
      constructs for cartilage repair. Chondrocyte-seeded agarose hydrogel constructs
      were cultured alone or attached to an underlying bony base in a chemically
      defined medium formulation that has been shown to yield engineered cartilaginous
      tissue with native Young's modulus (E(Y)) and glycosaminoglycan (GAG) content. By
      day 42 in culture the incorporation of a bony base significantly reduced these
      properties (E(Y)=87+/-12 kPa, GAG=1.9+/-0.8%ww) compared to the gel-alone group
      (E(Y)=642+/-97 kPa, GAG=4.6+/-1.4%ww). Similarly, the mechanical and biochemical
      properties of chondrocyte-seeded agarose constructs were inhibited when co
      cultured adjacent to bone (unattached), suggesting that soluble factors rather
      than direct cell-bone interactions mediate the chondro-inhibitory bone effects.
      Altering the method of bone preparation, including demineralization, or the
      timing of bone introduction in co-culture did not ameliorate the effects. In
      contrast, osteochondral constructs with native cartilage properties (E(Y)=730+/
      65 kPa, GAG=5.2+/-0.9%ww) were achieved when a porous tantalum metal base
      material was adopted instead of bone. This work suggests that devitalized bone
      may not be a suitable substrate for long-term cultivation of osteochondral
      grafts.

PMID- 18718656
TI  - The influence of RGD addition on the gene transfer characteristics of disulfide
      containing polyethyleneimine/DNA complexes.
AB  - Arginine-glycine-aspartic acid (RGD) ligand is often chemically attached to
      polycation vector to improve the transfection efficiency. However, the chemical
      reaction may reduce or even inactivate the biological activities of peptides. In
      order to retain the targeting ability and biological activities, the RGD peptide
      was noncovalently introduced into polycations as gene delivery systems. In this
      paper, the tripeptide sequence RGD was added to disulfide-containing
      polyethyleneimine (SS-PEI)/DNA binary complexes to evaluate the influence of RGD
      addition for the particle size, zeta potential, morphology, and transfection
      efficiency. GelRed was used as a molecular probe to show the effect of RGD
      addition on the cellular uptake of complexes. In vitro transfection experiments
      showed that SS-PEI exhibited comparable transfection efficiency, but lower
      cytotoxicity in comparison with 25kDa PEI. The transfection efficiency of
      complexes with RGD in HeLa cells was reduced statistically significantly with the
      increasing content of RGD peptide, but that in 293T cells was not altered
      significantly with the increasing content of RGD peptide. The reduced
      transfection efficiency of SS-PEI/DNA complexes with RGD in HeLa cells was
      attributed to the targeted binding interactions between the surplus RGD and the
      alpha(nu)beta(3) and alpha(nu)beta(5) integrins in HeLa cells, which would
      prevent the binding between RGD in complexes and integrin receptor on the surface
      of cells as well as nonspecific endocytosis of SS-PEI/DNA complexes mediated by
      proteoglycan in HeLa cells.

PMID- 18718657
TI  - Placental system A amino acid transport is reduced in pregnancies with small for
      gestational age (SGA) infants but not in preeclampsia with SGA infants.
AB  - Preeclampsia and intrauterine growth restriction (IUGR) are both associated with
      abnormal remodeling of maternal spiral arteries perfusing the placental site.
      This would be expected to be associated with reduced fetal growth, yet only one
      third of infants of mothers with preeclampsia are growth restricted. Infants with
      IUGR have decreased concentrations of amino acids in their blood and system A
      amino acid transporter activity is reduced in their placentas. Since infants of
      preeclamptic pregnancies have increased circulating amino acids, we tested system
      A amino acid transport activity of placental villous fragments from pregnancies
      with small for gestational age (SGA) infants with and without maternal
      preeclampsia and from uncomplicated and preeclamptic pregnancies with normal
      sized infants. We confirm the reduced uptake of amino acids in SGA pregnancies
      without preeclampsia but report that placental amino acid uptake of SGA infants
      with maternal preeclampsia is not reduced and is identical to uptake by normal
      and preeclamptic pregnancies with normal weight infants.

PMID- 18718658
TI  - Aggressive characteristics of myeloblasts expressing CD7 in myelodysplastic
      syndromes.
AB  - Clinical data suggest that CD7+ myeloblasts are linked with poor prognosis in
      myeloid malignancies including myelodysplastic syndromes (MDS). To explore the
      biology behind this, we compared cell characteristics between CD34+CD7+ and
      CD34+CD7- myeloblasts from an MDS cell line and fresh samples from MDS patients.
      Compared with CD34+CD7- myeloblasts, CD34+CD7+ myeloblasts showed greater
      proliferative capacity, more active cell cycling, and less apoptosis. In analyses
      of a cell line, CD34+CD7+ myeloblasts produced CD34+CD7- myeloblasts and showed
      lower expressions of interleukin-8 and chemokine (C-C motif) ligand 2 genes,
      suggesting immaturity of these cells. These findings might underlie the clinical
      aggressiveness in CD7+ MDS.

PMID- 18718659
TI  - Differential in vitro cytotoxicity does not explain increased host toxicities
      from chemotherapy in Down syndrome acute lymphoblastic leukemia.
AB  - Treatment-related toxicities such as mucositis and infections are both more
      frequent and more severe in children with Down syndrome (DS) and acute
      lymphoblastic leukemia (ALL) compared to non-DS ALL. Altered methotrexate
      pharmacodynamics play a role, but severe toxicities also occur in treatment
      courses that lack methotrexate. We hypothesized that this might be attributable
      to heightened cytotoxic effects of other ALL chemotherapeutic agents on DS versus
      non-DS host tissues. Panels of DS and non-DS lymphoblastoid cell lines (LCLs) and
      primary fibroblast cell lines were treated with asparaginase, dexamethasone,
      doxorubicin, mafosfamide and vincristine. LCL survival was assessed using the MTT
      assay, and fibroblast proliferation using the clonogenic survival assay. No
      significant differences were observed between DS and non-DS cell lines using
      either assay. Both DS and non-DS cell lines were resistant to dexamethasone at
      the maximal concentrations tested, and did not differ significantly in
      sensitivity to the other drugs studied. Thus, heightened in vitro cytotoxicity
      does not appear to account for the increased treatment-related toxicities
      observed in patients with DS ALL.

PMID- 18718660
TI  - Activation of c-Jun N-terminal kinase is essential for oxidative stress-induced
      Jurkat cell apoptosis by monochloramine.
AB  - Leukemic cell apoptosis may be enhanced by appropriate oxidative stress. We
      report here the mechanism of Jurkat cell apoptosis by monochloramine (NH(2)Cl), a
      neutrophil-derived oxidant. NH(2)Cl induced caspase-dependent apoptosis, which
      was preceded by cytochrome c and Smac/Diablo release from mitochondria. Within
      10min of NH(2)Cl treatment, c-Jun N-terminal kinase (JNK) activation and
      elevation of cytosolic Ca(2+) were observed. JNK inhibitors (SP600125 or JNK
      inhibitor VIII) significantly suppressed the apoptosis as well as caspase
      cleavage and cytochrome c release. In contrast, Ca(2+) chelation by
      EGTA+acetoxymethyl-EGTA had no effects on apoptosis. Our results indicated that
      JNK activation contributed most importantly to the NH(2)Cl-induced apoptosis.

PMID- 18718661
TI  - Ecological effects of the herbicide linuron in tropical freshwater microcosms.
AB  - Effects of a single application of the photosynthesis-inhibiting herbicide
      linuron (0, 15, 50, 150, and 500 microg/L) on the ecology of outdoor plankton
      dominated microcosms were studied in Thailand. As a result of the decreased
      photosynthesis, DO and pH decreased while EC, alkalinity and nutrient
      concentrations increased. Chlorophytes belonging to the genera Scenedesmus,
      Coelastrum and Pediastrum were the most sensitive taxa, whereas several other
      chlorophytes, diatoms, and cryptophytes increased in abundance. Tolerant taxa
      appeared to be less digestable for several zooplankton taxa, which subsequently
      decreased in abundances. Chamaesiphon sp. (Cyanobacteria) was the most
      susceptible periphyton species. As a consequence of functional redundancy,
      effects of the herbicide on the chlorophyll-a content of periphyton and
      especially phytoplankton did not always reflect the effects noted on community
      level.

PMID- 18718662
TI  - Cloning, nucleotide sequence and phylogenetic analyses, and tissue-specific
      expression of the transferrin gene in Cirrhinus mrigala infected with Aeromonas
      hydrophila.
AB  - Transferrin partial complementary DNAs were cloned from the livers of five
      species in four genera of Indian carps (Indian major carp species: Labeo rohita,
      Catla catla and Cirrhinus mrigala; medium carp: Puntius sarana; minor carp: Labeo
      bata) subsequent to polymerase chain reaction amplification with published
      heterologous primers or self-designed primers derived from conserved regions of
      transferrin cDNA sequences. The partial transferrin cDNAs of the five species of
      carps had sizes from 624 to 633bp (487bp for L. rohita) and encoded an open
      reading frame consisting of 206-211 (162 for L. rohita) amino acids. The
      alignments of carp cDNA sequences showed 85-97% homology and 71-93% homology in
      deduced amino acid sequences. A phylogenetic tree of amino acid sequences of
      transferrin cDNAs from carps showed that the relationship among the four genera
      of Indian carps is well correlated with that derived from classic morphologic
      analyses. The hypothesized cleavage site and interdomain bridge of transferrin
      molecule were predicted for the above carp species and interestingly the cleavage
      site amino acid sequence was found to be conserved among all the carps. To study
      the tissue-specific expression of the transferrin gene, various tissues (liver,
      kidney, spleen, brain, muscle, testis, heart, intestine, gill and fin) from
      apparently healthy (control), moribund and survived C. mrigala experimentally
      infected with Aeromonas hydrophila infection were analyzed. Transferrin mRNA was
      detected only in liver RNA and to lesser extent in brain tissue out of the 10
      tissues analyzed irrespective of bacterial infection.

PMID- 18718663
TI  - A preliminary survey of household and personal carbon dioxide emissions in
      Ireland.
AB  - A model specifically designed for Ireland was used to measure CO(2)e emissions
      (CO(2), CH(4) and N(2)O) from Irish households for the first time. A total of 103
      Irish households with occupancy rates varying between 1 and 6 (mean 2.9) were
      surveyed. The average annual household emission was found to be 16.55 t CO(2)e y(
      1), which is equivalent to an average personal emission of 5.70 t CO(2)e Ca(-1)
      y(-1) comprising 42.2% related to home energy use, 35.1% to transport, 20.6% to
      air travel and other fuel intensive leisure activities, and just 2.1% associated
      with household waste disposal. Air travel accounts for an average personal
      emission of 1.152 t CO(2)e Ca(-1) y(-1), although this is highest in single and
      two person households at 1.693 and 2.227 t CO(2)e Ca(-1) y(-1) respectively.
      Household energy consumption becomes more efficient when occupancy rate
      increases. The most energy efficient homes in the survey were terraced with a
      natural gas heating systems. The least efficient were detached house with oil
      fuelled heating system.

PMID- 18718664
TI  - Organochlorine pesticide and polychlorinated biphenyl residues in feathers of
      birds from different trophic levels of South-West Iran.
AB  - Persistent organochlorine pesticides (OCPs), such as
      dichlorodiphenyltrichloroethane (DDT) and its metabolites, hexachlorobenzene
      (HCB), alpha, beta and gamma-hexachlorocyclohexane (HCH) isomers, together with
      polychlorinated biphenyl (PCB) congeners (IUPAC Nos. 28, 52, 101, 138, 153 and
      180), were determined in tail feathers from 37 birds belonging to 18 species, all
      originating from the South-West of Iran (Khuzestan, coast of the Persian Gulf).
      This is the first report on organochlorine contaminants in feathers from museum
      collections and it is an indication of the concentrations of OCPs and PCBs in the
      past (1991-1996). Median concentrations of HCHs, DDTs, PCBs and HCB were 22, 14,
      11 and 10 ng/g feather, respectively. Significant correlations (p<0.05) were
      calculated between OCPs (except HCB) and PCBs in the bird feathers. p,p'-DDE and
      gamma-HCH were the most abundant OCPs, while CB 180, CB 138 and CB 101 were the
      predominant PCB congeners in almost all species. Significant differences (p<0.05)
      in the mean concentrations of DDTs and PCBs were detected among species grouped
      according to their feeding habits. Levels of DDTs and PCBs were highest in the
      carnivorous species and lowest in the herbivorous species. Levels of OCPs and
      PCBs in feathers of bids in the 1990s were generally below the thresholds
      reported to affect reproduction.

PMID- 18718665
TI  - Ongoing somatic hypermutation of the rearranged VH but not of the V-lambda gene
      in EBV-transformed rheumatoid factor-producing lymphoblastoid cell line.
AB  - Epstein-Barr virus (EBV) transforms human peripheral B cells into lymphoblastoid
      cell lines (LCLs) that secrete specific antibodies. In contrast to peripheral
      blood B cells, LCLs express the activation-induced cytidine deaminase (AID) gene,
      a key enzyme in the generation of somatic hypermutation (SHM) in immunoglobulin
      variable genes. We have previously studied an LCL that secretes a rheumatoid
      factor (RF: an IgM(lambda) anti-IgG antibody) and identified the accumulation of
      SHM at a frequency of 1.5 x 10(-3)mut/bp in the rearranged variable region heavy
      chain gene (VH) of its RF sub-culture (i.e., RF-2004). The aim of the present
      work was to find out whether SHM was initiated as an early event following EBV
      transformation. Our results show that already the earliest RF-culture (RF-1983)
      mutates its VH at a somewhat higher frequency of 1.9 x 10(-3). Overall, we
      detected 17 point mutations in the RF-2004 culture and in 26 cellular clones
      derived from the RF-1983 and RF-2004 cultures. Most of the mutations were due to
      C to T or G to A transitions, with preferential targeting to WRCH/DGYW hotspot
      motifs, indicating that they were due to the initial phase of AID-directed
      mutations. A genealogical tree demonstrates that mutations were accumulated in a
      stepwise manner with 1-2 mutations per cell division. However, no mutations were
      found in the rearranged V-lambda (Vlambda) gene in the same RF-cultures and their
      subclones (i.e., <1.2 x 10(-4)mut/bp). To our knowledge this is the first
      reported clonal cell line that generates SHM in the VH, but not in the Vlambda.
      It may be due to abrogation of a cis-regulatory element(s) in the Vlambda or to a
      lack of a specific trans-acting factor which differentially direct the SHM
      machinery to this gene. Out of the 17 point mutations detected in both cell lines
      there were, 1 stop codon, 3 mutations which obliterated the binding of the RF
      antibody to its IgG antigen and 1 or 2 mutations which enhanced antigen-binding
      affinity. These results show that the evolutionary developed germline encoded
      antibody combining site is highly sensitive to amino acid replacements. Our
      combined findings that the RF cells accumulate in a stepwise manner up to 1-2
      point mutations/sequence per cell division and the generation of high percentage
      of functionally deleterious mutations, are in accord with the 'multiphase
      recycling model' of SHM, which states that B cells in the germinal center are
      subjected to multiple rounds of somatic mutations interchanged with periods of
      antigenic selection.

PMID- 18718666
TI  - Role of soluble vascular endothelial growth factor receptor-1 in the vitreous in
      proliferative diabetic retinopathy.
AB  - PURPOSE: To determine the vitreous level of soluble vascular endothelial growth
      factor receptor-1 (sVEGFR-1) in patients with proliferative diabetic retinopathy
      (PDR) or idiopathic macular hole (MH). Furthermore, to investigate the
      relationships among sVEGFR-1, vascular endothelial growth factor (VEGF), and
      pigment epithelium-derived factor (PEDF). DESIGN: Retrospective case-control
      study. PARTICIPANTS: Thirty-eight patients who underwent vitrectomy (PDR [27 eyes
      in 26 patients] or MH [12 eyes in 12 patients]). METHODS: In vitreous fluid
      samples obtained during vitreoretinal surgery, sVEGFR-1, VEGF, and PEDF levels
      were measured by enzyme-linked immunosorbent assay. Effects of sVEGFR-1 on VEGF-A
      induced tube formation were investigated using human umbilical vein endothelial
      cells co-cultured with fibroblasts. MAIN OUTCOME MEASURES: Levels of sVEGFR-1 and
      the relationships among sVEGFR-1, VEGF, and PEDF in vitreous fluids from patients
      with PDR or MH. RESULTS: In PDR (vs MH), there were significantly higher vitreous
      concentrations of both sVEGFR-1 (3949.4+/-608.9 pg/mL [mean +/- standard error, n
      = 27] vs 1568.8+/-595.0 pg/mL [n = 12, P = 0.009]) and VEGF (1316.2+/-404.6 pg/mL
      [n = 27] vs 11.7+/-8.1 pg/mL [n = 12, P = 0.003]), whereas the vitreous
      concentration of PEDF was significantly lower (2.1+/-1.1 ng/mL [n = 27] vs 41.6+/
      17.0 ng/mL [n = 12, P = 0.041]). In PDR, there was a significant positive
      correlation between the sVEGFR-1 and VEGF vitreous concentrations (r = 0.414, P =
      0.032), but not between PEDF and VEGF (r = 0.196, P = 0.328) or between sVEGFR-1
      and PEDF (r = 0.167, P = 0.406). In vitro, sVEGFR-1 (0.1-1000 ng/mL)
      concentration-dependently inhibited VEGF-A-induced tube formation, its effect
      being significant at 100 to 1000 ng/mL on the tube area, length, and path.
      CONCLUSIONS: In the vitreous fluids of patients with PDR, the sVEGFR-1 level was
      increased (vs that in patients with MH), and sVEGFR-1 correlated significantly
      with VEGF. In vitro, sVEGFR-1 reduced VEGF-induced angiogenesis. Thus, sVEGFR-1
      may play a pivotal antiangiogenic role in PDR.

PMID- 18718668
TI  - Changes in the internal structure of the human crystalline lens with diabetes
      mellitus type 1 and type 2.
AB  - PURPOSE: To investigate the effect of diabetes mellitus (DM) type 1 and type 2 on
      the internal structure of the lens. DESIGN: Observational cross-sectional study.
      PARTICIPANTS AND CONTROLS: One hundred seven patients with DM type 1, 106
      patients with DM type 2, and 75 healthy control subjects. METHODS: Scheimpflug
      photography was used to image the lens of the right eye of 213 patients with DM
      and 75 healthy control subjects. The densitogram of the Scheimpflug image was
      used to indicate the nucleus and the different layers of the cortex of the lens.
      Lenses with cataract were excluded. MAIN OUTCOME MEASURES: The size of the
      nucleus and the different layers of the cortex of the lens. RESULTS: The nucleus
      and the different cortical layers of the DM type 1 lenses were significantly
      thicker compared with those of the control group (P<0.001). A significant
      association was found between the duration of DM type 1 and both the anterior and
      posterior cortex, its different layers, and the nucleus (P<0.001). The increase
      in the anterior and posterior cortex with the duration of DM was comparable with
      that of the nucleus. No important differences in the internal structure of the
      lens were found between the patients with DM type 2 and the control group.
      CONCLUSIONS: Diabetes mellitus type 1 has a significant effect on the internal
      structure of the lens. The difference in effect of DM type 1 and type 2 on
      internal lens structure suggests an essential difference in pathogenesis.
      Furthermore, the results of the present study may indicate that the increase in
      the size of the lens with DM type 1 is the result of a generalized swelling of
      the lens, affecting all its different parts.

PMID- 18718669
TI  - Synthesis, structure and antitumor activity of [RhCl3(N-N)(DMSO)] polypyridyl
      complexes.
AB  - The [RhCl(3)(N-N)(DMSO)] complexes, the N-N being 2,2'-bipyridine (1), 1,10
      phenanthroline (2), 4,7-diphenyl-1,10-phenanthroline (3), 4,4'-dimethyl-2,2'
      bipyridine (4) and 1,10-phenanthroline-5,6-dione (5), have been synthesized and
      characterized with spectroscopic methods. The compounds 2-5 adopt mer- and
      complex 1 fac-structure. The molecular and electronic structure studies of mer-
      and fac-complexes with bpy and phen ligands at the DFT B3LYP level with 3-21G( *
      *) basis set showed that mer-isomers are more stable. The cytostatic activity of
      the [RhCl(3)(N-N)(DMSO)] complexes against Caco-2 and A549 tumor cells have been
      studied. Their antibacterial activity have also been investigated. It has been
      found that the very promising biological activity show complexes 2, 3 and 4.

PMID- 18718667
TI  - The HtrA1 promoter polymorphism, smoking, and age-related macular degeneration in
      multiple case-control samples.
AB  - OBJECTIVE: To assess the association and combined effect on the risk of age
      related macular degeneration (AMD) by the HtrA1 and complement factor H (CFH)
      polymorphisms, smoking, and serum cholesterol. DESIGN: Clinic-based and
      population-based case control study. PARTICIPANTS: A total of 805 AMD cases and
      921 controls from The Eye Clinic of National Eye Institute, Age-Related Eye
      Diseases Study, Blue Mountain Eye Study Cohort, and Minnesota Lions Eye Bank.
      METHODS: DNA samples were genotyped for polymorphisms of rs11200638 in HtrA1
      promoter and rs380390 in CFH. HtrA1 protein in ocular tissue was measured.
      Interactions of the HtrA1 risk allele with the CFH risk variant, smoking status,
      and cholesterol were assessed. MAIN OUTCOME MEASURES: AMD was evaluated by
      retinal specialists, and AMD subtypes (geographic atrophy and neovascularization)
      were determined. RESULTS: Strong associations of the HtrA1 risk allele (A) with
      AMD were present in all sample sets. A similar magnitude of association was
      observed for central geographic atrophy and neovascular AMD. The combination of
      the HtrA1 and CFH risk alleles increased AMD susceptibility, as did the
      combination of the HtrA1 risk allele with smoking. No combined effect of HtrA1
      risk allele and cholesterol level was found. Enhanced expression of HtrA1 protein
      was detected in retina with AMD. CONCLUSIONS: Findings from multiple samples
      support an AMD genetic variant harbored within HtrA1. The risk of advanced AMD
      increased when the presence of risk alleles from HtrA1 was combined with either
      CFH risk alleles or history of smoking.

PMID- 18718670
TI  - Alexithymia in healthy women: a brain morphology study.
AB  - BACKGROUND: Alexithymia relates to difficulty recognizing and describing own
      feelings. Recent literature shows that specific structures process emotions. Aim
      of this study was to investigate whether alexithymia is associated with a
      specific cerebral morphology of candidate structures in healthy adults. METHODS:
      Fifty-four female volunteers were enrolled in the study and the 20-item Toronto
      Alexithymia Scale (TAS-20) was self-administered. Gray matter (GM) volume was
      assessed with an optimized voxel-based morphometry (VBM) protocol on high
      resolution 3D magnetic resonance images. The following three experiments were
      carried out: 1) contrast between the 14 volunteers with TAS-20 scores > or = 61
      (alexithymic) and the 30 with scores < 51 (non-alexithymic), 2) correlation of
      TAS-20 scores on the whole sample and 3) contrast between the 14 alexithymic and
      14 non-alexithymic matched by age. The significant threshold for VBM comparisons
      and correlation was set at p<0.005 uncorrected. RESULTS: The alexithymic group
      showed smaller GM volume in the anterior cingulate cortex (cluster size: 735
      voxel no.; z=3.26; stereotaxic coordinates: -12, 22, 30) and middle temporal
      gyrus (256; 3.21; -60, 2, -20). Of specific biological relevance, smaller
      clusters were located in the anterior insula, orbitofrontal cortex and superior
      temporal sulcus. The opposite comparison was negative. The correlation analysis
      confirmed the pattern of results mainly in the left hemisphere. CONCLUSIONS: Our
      findings suggest that the ability to process emotional aspects of the self
      correlates with morphology of a specific set of cerebral structures known to be
      involved in decision making and self awareness and rich in neurons subserving
      social competence.

PMID- 18718671
TI  - Assessing reliability and validity of the Arabic language version of the Post
      traumatic Diagnostic Scale (PDS) symptom items.
AB  - Arab immigrant women are vulnerable to post-traumatic stress disorder (PTSD)
      because of gender, higher probability of being exposed to war-related violence,
      traditional cultural values, and immigration stressors. A valid and reliable
      screen is needed to assess PTSD incidence in this population. This study
      evaluated the reliability and validity of an Arabic language version of the
      symptom items in Foa et al.'s [Foa, E.B., Cashman, L., Jaycox, L., and Perry, K.
      1997. The validation of a self report measure of posttraumatic stress disorder:
      the Posttraumatic Diagnostic Scale. Psychological Assessment 9(4), 445-451]. Post
      traumatic Diagnostic Scale (PDS) in a sample of Arab immigrant women (n=453).
      Reliability was supported by Cronbach's alpha values for the Arabic language
      version (0.93) and its subscales (0.77-0.91). Results of group comparisons
      supported validity: Women who had lived in a refugee camp or emigrated from Iraq 
      a country where exposure to war and torture is common - were exhibiting
      depressive symptoms (Center for Epidemiological Studies-Depression Scale (CES-D)
      score above 18), or reported moderately to severely impaired functioning had
      significantly higher mean PDS total and symptom subscale scores than women who
      had not had these experiences or were not exhibiting depressive symptoms. Scores
      on the PDS and its subscales were also positively correlated with the Profile of
      Mood States (POMS) depression and anxiety subscales and negatively correlated
      with the POMS vigor subscale (r=-.29 to-.39).

PMID- 18718672
TI  - Is low IQ related to risk of death by homicide? Testing a hypothesis using data
      from the Vietnam Experience Study.
AB  - Lower IQ test scores are related to an increased risk of violent assault. We
      tested the relation between IQ and death by homicide. In a prospective cohort
      study of 14,537 men (21 homicides), the association between lower IQ and an
      increased risk of homicide was lost after multiple adjustment.

PMID- 18718673
TI  - Comparison of data analysis strategies for intent-to-treat analysis in pre-test
      post-test designs with substantial dropout rates.
AB  - The pre-test-post-test design (PPD) is predominant in trials of psychotherapeutic
      treatments. Missing data due to withdrawals present an even bigger challenge in
      assessing treatment effectiveness under the PPD than under designs with more
      observations since dropout implies an absence of information about response to
      treatment. When confronted with missing data, often it is reasonable to assume
      that the mechanism underlying missingness is related to observed but not to
      unobserved outcomes (missing at random, MAR). Previous simulation and theoretical
      studies have shown that, under MAR, modern techniques such as maximum-likelihood
      (ML) based methods and multiple imputation (MI) can be used to produce unbiased
      estimates of treatment effects. In practice, however, ad hoc methods such as last
      observation carried forward (LOCF) imputation and complete-case (CC) analysis
      continue to be used. In order to better understand the behaviour of these methods
      in the PPD, we compare the performance of traditional approaches (LOCF, CC) and
      theoretically sound techniques (MI, ML), under various MAR mechanisms. We show
      that the LOCF method is seriously biased and conclude that its use should be
      abandoned. Complete-case analysis produces unbiased estimates only when the
      dropout mechanism does not depend on pre-test values even when dropout is related
      to fixed covariates including treatment group (covariate-dependent: CD). However,
      CC analysis is generally biased under MAR. The magnitude of the bias is largest
      when the correlation of post- and pre-test is relatively low.

PMID- 18718674
TI  - Temporal sequence of clinical manifestation in schizophrenia with co-morbid OCD:
      review and meta-analysis.
AB  - Obsessive-compulsive disorder (OCD) is often a comorbidity in schizophrenia
      (SCZ), but little is known about whether OCD emerges before or after a diagnosis
      of SCZ in the absence of atypical antipsychotic medications. The authors analyzed
      data from clinical studies reporting the temporal sequence of OCD and SCZ in
      comorbid patients to determine if there was a significant statistical difference
      between the mean ages of onset in both disorders and the percentage of patients
      diagnosed with OCD before SCZ. A MEDLINE search was conducted using the keywords
      "OCD" and "Schizophrenia." Studies were assessed for the presence of data
      regarding the ages of onset of patients comorbid with both disorders as well as
      the number of patients in each study diagnosed with OCD first, SCZ first, or both
      disorders concurrently. A meta-analysis was performed to test the a priori
      hypothesis that OCD is diagnosed before SCZ in patients who are comorbid with
      both disorders. There was no statistically significant difference in the
      unstandardized difference in the mean age of onset of OCD and SCZ. A strong trend
      in the data exists suggesting that the onset of OCD precedes SCZ. Future
      prospective studies with larger sample sizes are warranted.

PMID- 18718675
TI  - The relation between anger management style, mood and somatic symptoms in anxiety
      disorders and somatoform disorders.
AB  - The objective of this study was to examine the relationship between anger
      management style, depression, anxiety and somatic symptoms in anxiety disorder
      and somatoform disorder patients. The subjects comprised 71 patients with anxiety
      disorders and 47 with somatoform disorders. The level of anger expression or
      anger suppression was assessed by the Anger Expression Scale, the severity of
      anxiety and depression by the Symptom Checklist-90-Revised (SCL-90-R) anxiety and
      depression subscales, and the severity of somatic symptoms by the Somatization
      Rating Scale and the SCL-90-R somatization subscale. The results of path analyses
      showed that anger suppression had only an indirect effect on somatic symptoms
      through depression and anxiety in each of the disorders. In addition, only
      anxiety had a direct effect on somatic symptoms in anxiety disorder patients,
      whereas both anxiety and depression had direct effects on somatic symptoms in
      somatoform disorder patients. However, the anxiety disorder group showed a
      significant negative correlation between anger expression and anger suppression
      in the path from anger-out to anger-in to depression to anxiety to somatic
      symptoms, unlike the somatoform disorder group. The results suggest that anger
      suppression, but not anger expression, is associated with mood, i.e. depression
      and anxiety, and somatic symptoms characterize anxiety disorder and somatoform
      disorder patients. Anxiety is likely to be an important source of somatic
      symptoms in anxiety disorders, whereas both anxiety and depression are likely to
      be important sources of somatic symptoms in somatoform disorders. In addition,
      anger suppression preceded by inhibited anger expression is associated with
      anxiety and somatic symptoms in anxiety disorders.

PMID- 18718676
TI  - The influence of 5-HT(2C) and MDR1 genetic polymorphisms on antipsychotic-induced
      weight gain in female schizophrenic patients.
AB  - We investigated the relationships between functional genetic variants of the 5
      HT(2C) receptor and multidrug-resistant protein (MDR1), coding for P
      glycoprotein, and second generation antipsychotic (SDA)-induced weight gain among
      108 female schizophrenic patients treated with olanzapine or risperidone for up
      to 4 months. No significant differences in -759C/T allelic and genotype variants
      of 5-HT(2C) were found between patients who gained more than 7% of their initial
      weight compared with those who gained less. Haplotype-based analysis of two MDR1
      loci, exon 21 G2677T and exon 26 C3435T, revealed a slightly lower representation
      of the G2677/C3435 haplotype in the >or=7% group. In the subgroup of patients
      treated with risperidone, we found borderline overrepresentation of 2677T,
      significant overrepresentation of 3435T variant and borderline overrepresentation
      of 2677T/3435T haplotype the >or=7% group, whereas G2677/C3435 haplotype was
      found to be less represented in the >or=7% group. Our data indicate a
      nonsignificant role of 759C/T 5-HT(2C) in SDA-induced weight gain, and a stronger
      influence of the MDR1 G2677T and C3435T polymorphisms on risperidone-induced
      weight gain in female schizophrenic patients. 3435T and 2677T MDR1 variants, both
      associated with lower P-gp function, might predispose to higher risperidone
      accessibility to the brain that would lead to stronger effects, including weight
      gain.

PMID- 18718677
TI  - Abnormal orientation of Amplatzer PDA device on a chest radiogram masking foreign
      body aspiration.
AB  - Foreign body aspiration and consequent atelectasis of the lower lobe of the left
      lung with rotation of the heart resulted in an unusual radiographic appearance in
      a young girl who had recently undergone transcatheter closure of a patent
      arterial duct and coil embolization of an aortopulmonary collateral. The
      patient's chest radiography, who was originally admitted at a center with no
      echocardiography availability, was interpreted as showing embolization of one or
      both devices. Only clinical evaluation and echocardiography confirmed appropriate
      device position. Subsequently, foreign body aspiration was suspected and
      confirmed at bronchoscopy, and successfully treated. Atelectasis resolved within
      few days.

PMID- 18718679
TI  - Esophageal mucoceles causing airway obstruction as a complication of esophageal
      diversion: two rare pediatric cases and a review of the literature.
AB  - An esophageal mucocele causing airway obstruction is an exceptionally rare
      complication of esophageal diversion in children. In this instance, they are
      fluid-filled dilatations of the esophageal remnant following bipolar exclusion of
      the thoracic esophagus. Only six pediatric cases have been reported previously in
      the literature. We present two consecutive cases of esophageal mucoceles causing
      respiratory distress in children following surgical exclusion of the esophagus.
      Bronchoscopy followed by imaging (computerized tomography or magnetic resonance
      imaging) was used to reach the diagnosis. Complete resection of the thoracic
      esophagus was required in both patients. Esophageal mucoceles can occur many
      years after esophageal exclusion, and the clinical features are often non
      specific. Furthermore, complex co-morbidities may mask the underlying etiology of
      the respiratory distress, thus the diagnosis may be difficult to delineate. A
      high degree of suspicion, clinical awareness, and the use of the proper
      diagnostic tools, are essential for a diagnosis of mucoceles in children with a
      past history of esophageal exclusion.

PMID- 18718678
TI  - Parental perceptions and morbidity: tracheostomy and Pierre Robin sequence.
AB  - OBJECTIVE: Evaluate parental perceptions associated with tracheostomy morbidity
      and quality of life in the management of Pierre Robin Sequence (PRS). STUDY
      DESIGN: Retrospective review/survey. METHODS: 42 Pierre Robin patients were
      identified, records were reviewed and airway assessments evaluated relative to
      airway compromise. Twenty patients had undergone tracheostomy. Perceptions of
      quality of life/morbidity related to tracheostomy were assessed using parental
      surveys. RESULTS: 31/41 (76%) patients participated in the survey. 15/31 (48%) of
      survey participants required tracheostomy and were decannulated after a mean of
      28 months. Of the patients who had undergone tracheostomy, 10/15 (67%) had
      isolated Pierre Robin (iPRS) and the remaining 5/15 (33%) had syndromes
      associated with Pierre-Robin (sPRS). 9/10 (90%) iPRS and 4/5 (80%) sPRS families'
      expectations were met regarding expected duration of tracheostomy although 3/5
      (60%) sPRS, and 8/10 (80%) iPRS described the overall experience as difficult. Of
      the 2/15 patient's families who were dissatisfied 1 patient had iPRS and the
      other sPRS. 9/15 (60%) required multiple > or = 3) hospitalizations. 3/13 (23%)
      reported airway problems after decannulation and 2/15 (13%) remained tracheostomy
      dependent at the time of survey. Prolonged tracheostomy duration represented a
      significant parental concern. CONCLUSIONS: A subset of patients required extended
      duration of tracheostomy; some continued to have airway problems after
      decannulation and/or distraction. Although some patients benefit from early
      mandibular distraction other Pierre Robin patients have multi-level obstruction
      requiring additional therapies and often tracheostomy. Parental concerns and
      perceptions relative to tracheostomy have not been adequately studied for Pierre
      Robin airway obstruction. Of those responding to this survey, the majority of
      parents' expectations were met regarding tracheostomy. Of those whose
      expectations were not met, it seems that better pre-intervention counseling
      regarding length of tracheostomy tube dependence, as well as a discussion about
      potential complications and hospitalizations frequently associated with prolonged
      tracheostomy, may lead to improved parental expectations.

PMID- 18718680
TI  - Toxic effects of amoxicillin on the photosystem II of Synechocystis sp.
      characterized by a variety of in vivo chlorophyll fluorescence tests.
AB  - Amoxicillin is one of the widely used antibiotics of environmental concern. This
      study shows that amoxicillin has toxic effects on the photosynthesis of
      Synechocystis sp. Its inhibitory effects on photosystem II (PSII) of
      Synechocystis sp. were investigated by using a variety of in vivo chlorophyll
      fluorescence tests. The inhibitory effects of amoxicillin on PSII activity of
      Synechocystis sp. are concentration-dependent. Amoxicillin exposure leads to
      slowing down of electron transport on both donor side and acceptor side and
      causes accumulation of P680(+). Q(A)(-) reoxidation test revealed that
      amoxicillin hinders electron transfer from Q(A)(-) to Q(B)/Q(B)(-) and more Q(A)(
      ) is oxidized through S(2)(Q(A)Q(B))(-) charge recombination. Analysis of PSII
      heterogeneity demonstrated that an exposure to amoxicillin increases the
      proportion of inactive PSII (PSII(X)) centers and the proportion of PSII centers
      with small antenna (PSIIbeta). These changes finally result in deterioration of
      full photosynthesis performance.

PMID- 18718681
TI  - Cardiac computed tomographic angiography for risk stratification and prediction
      of late cardiovascular outcome events in patients with a chest pain syndrome.
AB  - BACKGROUND: Contrast-enhanced multidetector cardiac computed tomographic
      angiography (CCTA) has high sensitivity and specificity for diagnosing anatomic
      coronary stenoses, but its role in predicting late clinical outcome events has
      not been well studied. METHODS: We examined predictive value of CCTA for late
      major adverse cardiovascular (CV) outcome events (MACE)(CV death, myocardial
      infarction, myocardial revascularization) (follow-up 18.2+/-6.3, range 9-30
      months) in 545 consecutive symptomatic patients (368 (68%) men, 177 (32%) women)
      with clinical suspicion, but without previously diagnosed, coronary artery
      disease (CAD) who underwent 40- or 64-channel CCTA. RESULTS: MACE occurred in
      53/545 (9.7%) patients (early 30 day CCTA-driven events excluded): CV
      death/myocardial infarction in 3/327 (0.9%) patients with no coronary luminal
      narrowing >25% (group 1), in 3/127 (2.4%) with >or=1 luminal narrowing(s) of 26
      69% (group 2) and in 9/91 (9.9%) with >or=1 coronary luminal narrowing(s) of
      >or=70% (group 3) (p<0.0001). CV death/myocardial infarction/revascularization
      occurred in 5/327 (1.5%) group 1 patients, 19/127 (14.9%) group 2 and 29/91
      (31.9%) group 3 (p<0.0001). Multivariate analysis (adjusting for age, gender,
      coronary risk factors and coronary calcium score) identified CCTA stenosis (>25%)
      as a powerful independent predictor of MACE (HR 10.9, 95%CI 4.1-29.0, p<0.0001).
      CONCLUSIONS: CCTA was useful to predict late clinical outcome events in patients
      undergoing evaluation of a chest pain syndrome.

PMID- 18718682
TI  - Cardiac Papillary Fibroelastoma: case report and review of the literature.
AB  - Primary cardiac tumors are very rare. Cardiac Papillary Fibroelastoma (CPF) is
      the third most common primary tumor of the heart and most commonly affects
      cardiac valves. Those tumors appear like a "sea anemone" with multiple papillary
      fronds attached to the endocardium by a short stalk. It generally occurs as a
      single structure and is typically found on the atrial aspect of atrioventricular
      valves or either side of the semilunar valves. We report a case of aortic valve
      papillary fibroelastoma which was found on autopsy in a patient with normal
      coronary artery with evidence of myocardial and cerebral ischemic damage and
      sudden death.

PMID- 18718683
TI  - Percutaneous revascularization strategies in a patient with previous coronary
      artery bypass surgery: technical and patho-physiological insights.
AB  - Occasionally, in post-coronary artery bypass patients multiple percutaneous
      revascularization choices (treatment of the native artery versus treatment of the
      bypass graft) are available in order to obtain adequate blood supply of the
      ischemic myocardial region and relief of the anginal symptoms. Once a strategy
      has been chosen, the possibility to switch to the alternative plan should be
      considered in case unpredictable complications occur during the first treatment
      choice. A step-by-step assessment and prediction of the possible acute and long
      term outcomes and complications should always be performed in order to optimize
      the results.

PMID- 18718684
TI  - Thromboembolism in Takotsubo cardiomyopathy.
AB  - BACKGROUND: Most patients with Takotsubo cardiomyopathy show a favorable outcome.
      Although several complications have been reported, the frequency of
      thromboembolism has not been clarified. METHODS: Clinical characteristics and
      complications of 21 consecutive patients (18 female, aged 72 years) with
      Takotsubo cardiomyopathy during the past 9 years were investigated. RESULTS: The
      most major complication was heart failure (52%). Thromboembolism was found in 3
      patients (14%) and this was the second most frequent cardiovascular complication.
      One of the 3 patients showed left ventricular thrombus and the other 2
      experienced cardioembolic stroke. All 3 patients visited the emergency department
      more than 48 h after initial chest pain occurred. CONCLUSIONS: This study
      indicates that thromboembolism is a common complication in the acute phase of
      Takotsubo cardiomyopathy, and anticoagulation therapy should be performed in all
      patients until wall motion abnormalities improve. Takotsubo cardiomyopathy should
      be considered one of the important causes of cardioembolic stroke.

PMID- 18718686
TI  - Chill therapy in the patients with resuscitated cardiac arrest: a new weapon in
      the battle against anoxic brain injury.
AB  - Improved cooling technologies (such as newer intravascular cooling devices) may
      result in earlier attainment of target temperature and even more robust clinical
      benefits in the management of the survivors of cardiac arrest. Earlier cooling
      may also be facilitated by the introduction of cooled saline infusions in the
      emergency room setting, prior to induction of cooling in the intensive care unit.
      However, there is a need for studies of adjunctive therapies to minimize the risk
      of medical complications associated with hypothermia, the most serious of which
      is infection. We strongly believe that larger confirmatory studies might
      encourage more widespread adoption of therapeutic hypothermia for survivors of
      cardiac arrest and further studies are also needed to evaluate the utility of
      this procedure for more expanded indications, including asystole, pulseless
      electrical activity, and in-hospital arrest in patients without significant
      comorbidity.

PMID- 18718687
TI  - Coronary artery aneurysm and thrombosis following chronic ephedra use.
AB  - Ephedra, also known as Ma Huang, was commonly used to enhance athletic
      performance, "fat burning", and weight loss before its removal from the United
      States in April 2004 due to acute adverse health reactions including lethal
      arrhythmias, stroke, vasoconstriction, and myocardial infarction. We report the
      case of a 29-year-old patient with acute myocardial infarction, secondary to
      coronary artery aneurysms and thrombosis who reported use of Ma Huang,
      Xenadrine(r)RFA, and Hydroxycut at recommended dosages for a combined total of
      approximately 2 years. Other causes of coronary artery aneurysm and
      hypercoagulability were ruled out. Our case exemplifies the long-term (as opposed
      to acute) danger of ephedrine products and the first case of coronary artery
      aneurysm associated with its use.

PMID- 18718688
TI  - A study of presbycardia, with gender differences favoring ageing women.
AB  - BACKGROUND: The impact of ageing on the human cardiovascular system has been the
      subject of several studies in recent years, but with insufficient emphasis on
      defining sex-specific differences. To rectify this, gender-specific differences
      in structure and function in the human cardiovascular system were studied in a
      European population during natural ageing. METHODS: Cardiac power output (CPO)
      was measured and integrated with changes in left ventricular (LV) mass,
      diastolic, systolic and limb blood flow, blood pressure and exercise capacity in
      93 health-screened men and 122 women, aged 20 to 75 years. RESULTS: Correlating
      with a 21% loss of LV mass, maximum cardiac pumping (i.e. CPOmax=QmaxxMAPmax) and
      reserve (CR=CPOmax-CPOrest) capacities decreased 20-25% with age in male hearts.
      In contrast, CPOmax, CR and LV mass were all preserved in ageing women. Maximum
      cardiac output (Qmax; 26-32%), peak forearm blood flow (FBFpeak; 61%) and
      exercise capacity (40-50%) all decreased, but more so in men than women. In
      contrast, systemic vascular resistance (68-75%) and mean arterial pressure
      (MAPmax; 14-26%) increased in both sexes. CPOrest decreased 27% in men, but was
      unchanged in women, despite lower early:late diastolic filling (48-51%), Qrest
      (19-23%) and FBFrest (56%) in both sexes. CONCLUSIONS: Understanding sex-specific
      differences in cardiovascular ageing is important for public health and
      biomedical research, given increasingly larger older populations and the need to
      prevent and treat cardiovascular disease.

PMID- 18718689
TI  - A cDNA-AFLP approach to study ochratoxin A production in Aspergillus carbonarius.
AB  - Aspergillus carbonarius is responsible for the majority of mycotoxin
      contaminations in grapes and its derivatives. Most of A. carbonarius strains are
      ochratoxin A (OTA) producers, even though at very different levels. This broad
      variability was used to identify genes whose expression is linked with the
      ability of producing OTA. A cDNA-AFLP differential display screening was
      performed in two strains of A. carbonarius, antagonists for the ability of
      producing OTA, allowing the identification of 119 differentially expressed
      sequences putatively involved in the regulation of OTA biosynthesis. A likely
      connection was pointed out between the biosynthesis of the toxin, vegetative
      growth and sexual/asexual developmental progression, along with common signalling
      pathways involving G protein and Ca2+/calmodulin dependent phosphorylation and
      dephoshorylation cascades.

PMID- 18718690
TI  - Choosing the best endpoint.
AB  - Design and endpoints of clinical trials in hepatocellular carcinoma. Llovet JM,
      Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M,
      Lotze M, Talwalkar J, Gores GJ; for the Panel of Experts in HCC-Design Clinical
      Trials. The design of clinical trials in hepatocellular carcinoma (HCC) is
      complex because many patients have concurrent liver disease, which can confound
      the assessment of clinical benefit. There is an urgent need for high-quality
      trials in this disease. An expert panel was convened by the American Association
      for the Study of Liver Diseases to develop guidelines that provide a common
      framework for designing trials to facilitate comparability of results. According
      to these guidelines, randomized phase 2 trials with a time-to-event primary
      endpoint, such as time to progression, are pivotal in clinical research on HCC.
      Survival remains the main endpoint to measure effectiveness in phase 3 studies,
      whereas time to recurrence is proposed as an appropriate endpoint in the adjuvant
      setting. Because progression-free survival and disease-free survival are
      composite endpoints, they are more vulnerable than others in HCC clinical studies
      and may not be able to capture clinical benefits. Selection of the target
      population should be based on the Barcelona Clinic Liver Cancer staging system.
      New drugs should be tested in patients with well-preserved liver function (Child
      Pugh A class). Patients assigned to the control arm should receive standard-of
      care therapy, that is, chemoembolization for patients with intermediate-stage
      disease and sorafenib for patients with advanced-stage disease. Further research
      is needed to incorporate biomarkers and molecular imaging into clinical research
      in HCC. These surrogate markers may help to enrich study populations and maximize
      the cost-benefit ratio of trial execution. Design and conduct of phase 3 trials
      should be coordinated by centers with appropriate expertise in HCC. [Abstract
      reproduced by permission of J Natl Cancer Inst 2008;100:698-711.] Link to free
      abstract at: (http://jnci.oxfordjournals.org/cgi/content/abstract/100/10/698).

PMID- 18718691
TI  - Computerized screening of children congenital heart diseases.
AB  - In this paper, we propose a method for automated screening of congenital heart
      diseases in children through heart sound analysis techniques. Our method relies
      on categorizing the pathological murmurs based on the heart sections initiating
      them. We show that these pathelogical murmur categories can be identified by
      examining the heart sound energy over specific frequency bands, which we call,
      Arash-Bands. To specify the Arash-Band for a category, we evaluate the energy of
      the heart sound over all possible frequency bands. The Arash-Band is the
      frequency band that provides the lowest error in clustering the instances of that
      category against the normal ones. The energy content of the Arash-Bands for
      different categories constitue a feature vector that is suitable for
      classification using a neural network. In order to train, and to evaluate the
      performance of the proposed method, we use a training data-bank, as well as a
      test data-bank, collectively consisting of ninety samples (normal and abnormal).
      Our results show that in more than 94% of cases, our method correctly identifies
      children with congenital heart diseases. This percentage improves to 100%, when
      we use the Jack-Knife validation method over all the 90 samples.

PMID- 18718694
TI  - Synthesis and in vitro antimicrobial activity of some novel substituted
      benzimidazole derivatives having potent activity against MRSA.
AB  - The novel benzimidazole derivatives (3, 5, 8, 9, 12-14, 18-41) were prepared in
      this paper and the antimicrobial activities of these compounds against
      Staphylococcus aureus, methicillin-resistant S. aureus (MRSA, standard and
      clinical isolates), Bacillus subtilis, Escherichia coli and Candida albicans were
      evaluated. Compounds 24-26 which have no substitution of N-1 position displayed
      better antibacterial activities than those of standards (ciprofloxacin,
      ampicillin and sultamicillin) against both the drug-resistant bacteria (MRSA,
      standard and clinical isolates). These derivatives (24-26), 2,5,6
      trihalogenobenzimidazole analogues (8, 12), 5,6-dichloro-2-amino derivative (13),
      and 5-chloro-2-(4-benzyloxyphenyl)benzimidazole (35) exhibited the most potent
      antibacterial activity with MIC 3.12 microg/ml against S. aureus.

PMID- 18718693
TI  - Leukocyte telomere length is associated with cognitive performance in healthy
      women.
AB  - BACKGROUND: Age-related cognitive decline begins in mid-life and continues with
      advancing age. Leukocyte telomere length (LTL) shortens with age, and
      inflammation and oxidative stress enhance this process. Shorter LTL is associated
      with dementia. METHODS: The relationship between cognitive function and LTL was
      investigated in a cross-sectional study of 382 women (mean age 50.6 years, range
      19-78), not diagnosed with any form of dementia or cognitive impairment, from the
      TwinsUK cohort using six tests from the Cambridge neuropsychological test
      automated battery (CANTAB). RESULTS: After adjusting for age and estimated prior
      intellectual ability, we observed significant correlations of LTL with episodic
      memory and associated learning (PAL, p=0.032), recognition memory for non-verbal
      patterns (DMS, p=0.007), and working memory capacity (SSP, p=0.003). In pairs of
      twins discordant for LTL the twin with longer telomeres also had significantly
      better DMS (p<0.05) and SSP (p<0.013) scores than their co-twin with shorter
      telomeres. The correlations between these two scores and LTL was significant both
      in women over the median mean age and in those below the median age, and remained
      significant after statistical adjustment for potential confounders. CONCLUSIONS:
      Leukocyte telomere length correlates with a subset of measures of cognitive
      performance, suggesting that it might be a biomarker of cognitive aging in women
      before the onset of dementia.

PMID- 18718692
TI  - A gene signature of nonhealing venous ulcers: potential diagnostic markers.
AB  - BACKGROUND: Venous leg ulcers are responsible for more than half of all lower
      extremity ulcerations. Significant interest has been focused on understanding the
      physiologic basis on which patients fail to heal with standard therapy.
      OBJECTIVE: This study uses complementary DNA microarray analysis of tissue
      samples from healing and nonhealing venous leg ulcers to identify the genetic
      expression profiles from these dichotomous populations. METHODS: Ulcer size and
      chronicity, factors that have been identified as prognostic indicators for
      healing, were used to distribute venous leg ulcers as healing versus nonhealing.
      Punch biopsy samples were obtained from the wound edge and wound bed of all
      venous leg ulcers. The top 15 genes with differential expression greater than 2
      fold between the two populations of wounds (P < .05) were reported. RESULTS:
      Significant differences were demonstrated in the expression of a diverse
      collection of genes, with particular differences demonstrated by genes coding for
      structural epidermal proteins, genes associated with hyperproliferation and
      tissue injury, and transcription factors. LIMITATIONS: Small sample size may
      mitigate potential clinical implications of findings. CONCLUSIONS: The genetic
      expression profiles displayed here may have implications for the development of
      novel therapies for chronic venous leg ulcers, and may also serve as prognostic
      indicators for wound healing.

PMID- 18718695
TI  - Microwave-induced synthesis and anti-microbial activities of 7,10,11,12
      tetrahydrobenzo[c]acridin-8(9H)-one derivatives.
AB  - Some new substituted tetrahydroacridin-8-ones and diverse derivatives were
      synthesized by uncatalysed multi-component reaction of dimedone or cyclohexan-1,3
      dione, alpha-naphthylamine and various (o,p,m)-substituted benzaldehydes. The in
      vitro anti-microbial activities of the prepared compounds were evaluated against
      some bacteria and fungi strains. The results suggested that, the products 2a-g
      and 4a-g exhibited good inhibitory effect against most of the tested organisms.
      Especially, 2f, 2g, 4f and 4g were shown to be most effective against Rhodotorula
      rubra and Aspergillus parasiticus and compounds 2a, 2c, 2g, 4f and 4g proved to
      be effective with MIC values in the range of 3.9-7.8 microg/ml.

PMID- 18718696
TI  - Cachexia: a new definition.
AB  - On December 13th and 14th a group of scientists and clinicians met in Washington,
      DC, for the cachexia consensus conference. At the present time, there is no
      widely agreed upon operational definition of cachexia. The lack of a definition
      accepted by clinician and researchers has limited identification and treatment of
      cachectic patient as well as the development and approval of potential
      therapeutic agents. The definition that emerged is: "cachexia, is a complex
      metabolic syndrome associated with underlying illness and characterized by loss
      of muscle with or without loss of fat mass. The prominent clinical feature of
      cachexia is weight loss in adults (corrected for fluid retention) or growth
      failure in children (excluding endocrine disorders). Anorexia, inflammation,
      insulin resistance and increased muscle protein breakdown are frequently
      associated with cachexia. Cachexia is distinct from starvation, age-related loss
      of muscle mass, primary depression, malabsorption and hyperthyroidism and is
      associated with increased morbidity. While this definition has not been tested in
      epidemiological or intervention studies, a consensus operational definition
      provides an opportunity for increased research.

PMID- 18718697
TI  - Organization of polyene antibiotic amphotericin B at the argon-water interface.
AB  - Amphotericin B (AmB) is a life-saving antibiotic, used to treat deep-seated
      mycotic infections. Both the therapeutic and toxic side effects of AmB are
      directly dependent on its molecular organization. Organization of AmB was studied
      in monocomponent monomolecular layers formed at the argon-water interface, by
      means of polarized and non-polarized electronic absorption spectroscopy and
      analyzed in terms of the exciton splitting theory. The results provide direct
      indication that AmB forms spontaneously dimers that can be assembled into
      molecular structures characterized by homogeneous orientational distribution in
      the monolayer, interpreted as cylindrical pores. The structures are not stable at
      surface pressures higher than 20 mN/m and therefore dimers are concluded as
      abundant molecular organization forms of AmB in biomembranes. Possibility of
      stabilization of the cylindrical structures, at higher surface pressures, by
      other molecules, e.g. sterols, is also discussed.

PMID- 18718698
TI  - Safety and efficacy of transcatheter closure of atrial septal defects guided by
      transthoracic echocardiography: a prospective study from two Chinese Medical
      Centers.
AB  - The purpose of this study was to evaluate the safety and efficacy of
      transcatheter atrial septal defect (ASD) closure guided by transthoracic
      echocardiography (TTE). A total of 191 patients with ASD were recruited from two
      Chinese medical centers and TTE was carefully performed in multiple views to
      observe ASD number, position, diameter and relation with adjacent cardiac
      structures. All patients were divided into three groups based on their largest
      ASD diameters: 66 subjects with ASD diameter 5-14 mm (group A); 60 subjects with
      ASD diameter 15-20 mm (group B); and 65 subjects with ASD diameter 21-38 mm
      (group C). Atrial septal occluders (ASOs) were successfully deployed in 188
      patients (98.4%) and ASD was successfully closed at 6-mo follow-up in 185
      patients (96.9%). The difference between diameters of ASO and ASD (ASO-ASD) in
      groups A, B and C were 3.9 +/- 2.4 (0-7) mm, 5.0 +/- 2.6 (3-8) mm and 6.2 +/- 3.8
      (5-11) mm, respectively. In group A, no complications occurred. In group B, only
      four patients had mild complications such as sinus bradycardia, transient
      hematuria and migraine, all of which disappeared after treatment. In group C, one
      patient developed ASO migration into the right atrium and two patients had their
      ASO migrated into the right ventricular outflow tract. Immediately after the
      closure, 60 (90.9%), 53 (88.3%) and 53 (82.8%) patients had complete ASD closure;
      2, 4 and 6 patients had trivial residual shunts; 4, 3 and 2 patients had small
      residual shunts; and 0, 0 and 2 patients had moderate residual shunts in groups
      A, B and C, respectively. Most of the residual shunts were persistent at 6-mo
      follow-up. No embolism or death at procedure and 6-mo follow-up occurred. In
      conclusion, TTE is a reliable technique for measurement of ASD diameter, guidance
      of transcatheter ASD closure and evaluation of residual shunts. Transcatheter ASD
      closure guided by TTE is safe and effective, especially in patients with ASD
      <or=20 mm.

PMID- 18718699
TI  - Prevalence of a tertiary Gleason grade and its impact on adverse histopathologic
      parameters in a contemporary radical prostatectomy series.
AB  - BACKGROUND: The presence of a tertiary Gleason grade (TGG) pattern in radical
      prostatectomy (RP) specimens has been described as associated with adverse
      pathology and a higher biochemical recurrence (BCR) rate after RP. OBJECTIVE: To
      assess the prevalence of a TGG in a contemporary, consecutive, single-centre RP
      series and its association with adverse pathology. DESIGN, SETTING, AND
      PARTICIPANTS: From January to August 2007, 800 eligible patients (no prior
      neoadjuvant hormonal therapy) underwent RP for clinically localised prostate
      cancer (pCA) in our institution. The presence of the third most prevalent Gleason
      pattern was documented, regardless of whether it was better or worse than the two
      predominant Gleason grades. MEASUREMENTS: The overall prevalence of a TGG was
      described. Uni- and multivariate logistic regression analyses tested the
      association between the presence of a TGG <5% versus >or=5% of the whole tumour
      volume and extracapsular extension (ECE), seminal vesicle invasion (SVI),
      positive surgical margins (PSM), and lymph node invasion (LNI). Subanalyses were
      performed to assess the impact of different TGGs at various Gleason scores.
      RESULTS AND LIMITATIONS: A TGG was reported in 180 RP specimens (22.5%). In
      univariate analysis, the presence of a TGG >/=5% was significantly associated
      with ECE, SVI, PSM, and LNI (p<0.001). In multivariate analysis, a TGG >or=5%
      showed an independent association with ECE and PSM (p<0.05). Accordingly, in
      subanalyses, a significant association with adverse pathology was only documented
      if the amount of a TGG was at least 5% of the tumour volume. Our study is limited
      by the relatively low overall frequency of a TGG, thereby reducing the
      statistical expressiveness, especially for subanalyses. CONCLUSIONS: Our findings
      confirm the association of the presence of a TGG with adverse pathologic
      features. Further follow-up is needed to assess the prognostic impact of a TGG on
      the risk of BCR and overall survival following RP.

PMID- 18718700
TI  - Editorial comment on: Prevalence of a tertiary Gleason grade and its impact on
      adverse histopathologic parameters in a contemporary radical prostatectomy
      series.

PMID- 18718701
TI  - Re: Claus G. Roehrborn, Steven A. Kaplan, J. Stephen Jones, Joseph T. Wang,
      Tamara Bavendam, Zhonghong Guan. Tolterodine extended release with or without
      tamsulosin in men with lower urinary tract symptoms including overactive bladder
      symptoms: effects of prostate size. Eur Urol 2009;55:472-81.

PMID- 18718702
TI  - Expression and localisation of aquaporin water channels in human urothelium in
      situ and in vitro.
AB  - BACKGROUND: Urothelium is generally considered to be impermeable to water and
      constituents of urine. The possibility that human urothelium expresses aquaporin
      (AQP) water channels as the basis for water and solute transport has not
      previously been investigated. OBJECTIVE: To investigate the expression of AQP
      water channels by human urothelium in situ, in proliferating urothelial cell
      cultures and in differentiated tissue constructs. DESIGN, SETTING, AND
      PARTICIPANTS: AQP expression by human urothelium in situ and cultured urothelial
      cells was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR)
      and immunolabelling. Expression screening was carried out on samples of freshly
      isolated urothelia from multiple surgical (bladder and ureteric) specimens and on
      proliferating and differentiated normal human urothelial (NHU) cells in culture.
      Urothelial tissue constructs were established and investigated for expression of
      urothelial differentiation markers and AQPs. MEASUREMENTS: Qualitative study.
      RESULTS AND LIMITATIONS: Transcripts for AQP3, AQP4, AQP7, AQP9, and AQP11 were
      expressed consistently by freshly isolated urothelia as well as by cultured NHU
      cells. AQP0, AQP1, AQP2, AQP5, AQP6, AQP8, AQP10, and AQP12 were not expressed.
      Immunochemistry confirmed expression of AQP3, AQP4, AQP7, and AQP9 at the protein
      level. AQP3 was shown to be intensely expressed at cell borders in the basal and
      intermediate layers in both urothelium in situ and differentiated tissue
      constructs in vitro. CONCLUSIONS: This is the first study to demonstrate that
      AQPs are expressed by human urothelium, suggesting a potential role in
      transurothelial water and solute transport. Our findings challenge the
      traditional concept of the urinary tract as an impermeable transit and storage
      unit and provide a versatile platform for further investigations into the
      biological and clinical relevance of AQPs in human urothelium.

PMID- 18718703
TI  - Editorial comment on: Prevalence of a tertiary Gleason grade and its impact on
      adverse histopathologic parameters in a contemporary radical prostatectomy
      series.

PMID- 18718704
TI  - Editorial comment on: Prevalence of a tertiary Gleason grade and its impact on
      adverse histopathologic parameters in a contemporary radical prostatectomy
      series.

PMID- 18718705
TI  - Re: Christian Walter, Bilal Al-Nawas, Knut A. Grotz, et al. Prevalence and risk
      factors of bisphosphonate-associated osteonecrosis of the jaw in prostate cancer
      patients with advanced disease treated with zoledronate. Eur Urol 2008;54:1066
      72.

PMID- 18718706
TI  - Editorial comment on: Expression and localization of aquaporin water channels in
      human urothelium in situ and in vitro.

PMID- 18718707
TI  - Current concepts in the diagnosis of transverse myelopathies.
AB  - The clinical symptoms and MRI characteristics of transverse myelopathy (TM) due
      to non-compressive causes are reviewed, with special emphasis on the differential
      diagnosis between inflammatory demyelinating lesions, and metabolic and vascular
      myelopathies. Inflammatory transverse myelopathies are the commonest and most
      difficult ones to identify. The differentiation between clinically isolated
      syndromes, multiple sclerosis, neuromyelitis optica, acute disseminated
      encephalomyelitis and metabolic causes is based on both clinical symptoms and
      paraclinical signs including magnetic resonance imaging, cerebrospinal fluid
      analysis, and immunological and biochemical parameters. The most intriguing form
      of TM is that where there is clinical evidence of complete spinal cord
      transection, with normal findings in magnetic resonance imaging in the acute
      phase, but subsequent cord atrophy.

PMID- 18718708
TI  - Histone deacetylase inhibitors sensitize tumour cells for cytotoxic effects of
      natural killer cells.
AB  - Histone deacetylase inhibitors (HDIs) are emerging as potent anti-tumour agents
      which induce cell cycle arrest, differentiation and/or apoptosis in many tumour
      cells. Furthermore, they render tumour cells more sensitive to other therapeutic
      regimens like ionizing radiation, chemotherapy and recombinant tumour necrosis
      factor-related apoptosis-inducing ligand (TRAIL). Here, we show that the HDIs
      suberoylanilide hydroxamic acid (SAHA; vorinostat), sodium butyrate (NaB) and MS
      275 sensitized DAOY and PC3 tumour cells for the cytotoxic effects of IL-2
      activated PBMCs. In (51)Cr-release assays, blockade of the activating NK
      receptors DNAM-1, NKG2D and the NCRs completely abrogated tumour cell lysis,
      revealing that NK cells were the main effector cells involved. HDIs increased the
      tumour surface expression of ligands for the activating NK receptors NKG2D and
      DNAM-1 thereby facilitating tumour cell recognition by NK cells. These results
      suggest that the combination of HDIs and immunotherapy may be an effective
      strategy for anti-cancer therapy.

PMID- 18718709
TI  - A novel biosorbent for dye removal: extracellular polymeric substance (EPS) of
      Proteus mirabilis TJ-1.
AB  - This paper deals with the extracellular polymeric substance (EPS) of Proteus
      mirabilis TJ-1 used as a novel biosorbent to remove dye from aqueous solution in
      batch systems. As a widely used and hazardous dye, basic blue 54 (BB54) was
      chosen as the model dye to examine the adsorption performance of the EPS. The
      effects of pH, initial dye concentration, contact time and temperature on the
      sorption of BB54 to the EPS were examined. At various initial dye concentrations
      (50-400 mg/L), the batch sorption equilibrium can be obtained in only 5 min.
      Kinetic studies suggested that the sorption followed the internal transport
      mechanism. According to the Langmuir model, the maximum BB54 uptake of 2.005 g/g
      was obtained. Chemical analysis of the EPS indicated the presence of protein
      (30.9%, w/w) and acid polysaccharide (63.1%, w/w). Scanning electron microscopy
      (SEM) images showed that the EPS with a crystal-linear structure was whole
      enwrapped by adsorbed dye molecules. FTIR spectrum result revealed the presence
      of adsorbing groups such as carboxyl, hydroxyl and amino groups in the EPS. High
      molecular weight of the EPS with more binding-sites and stronger van der Waals
      forces together with its specific construct leads to the excellent performance of
      dye adsorption. The EPS shows potential board application as a biosorbent for
      both environmental protection and dye recovery.

PMID- 18718710
TI  - Physio-chemical reactions in recycle aggregate concrete.
AB  - Concrete waste constitutes the major proportion of construction waste at about
      50% of the total waste generated. An effective way to reduce concrete waste is to
      reuse it as recycled aggregate (RA) for the production of recycled aggregate
      concrete (RAC). This paper studies the physio-chemical reactions of cement paste
      around aggregate for normal aggregate concrete (NAC) and RAC mixed with normal
      mixing approach (NMA) and two-stage mixing approach (TSMA) by differential
      scanning calorimetry (DSC) and scanning electron microscopy (SEM). Four kinds of
      physio-chemical reactions have been recorded from the concrete samples, including
      the dehydration of C(3)S(2)H(3), iron-substituted ettringite, dehydroxylation of
      CH and development of C(6)S(3)H at about 90 degrees C, 135 degrees C, 441 degrees
      C and 570 degrees C, respectively. From the DSC results, it is confirmed that the
      concrete samples with RA substitution have generated less amount of strength
      enhancement chemical products when compared to those without RA substitution.
      However, the results from the TSMA are found improving the RAC quality. The pre
      mix procedure of the TSMA can effectively develop some strength enhancing
      chemical products including, C(3)S(2)H(3), ettringite, CH and C(6)S(3)H, which
      shows that RAC made from the TSMA can improve the hydration processes.

PMID- 18718711
TI  - Role of oxygen active species in the photocatalytic degradation of phenol using
      polymer sensitized TiO2 under visible light irradiation.
AB  - The role of dissolved oxygen, and of active species generated by photo-induced
      reactions with oxygen, in the photocatalytic degradation of phenol was
      investigated using polymer [poly-(fluorene-co-thiophene) with thiophene content
      of 30%, so-called PFT30] sensitized TiO2 (PFT30/TiO2) under visible light
      irradiation. The photoluminescent (PL) quantum yield of PFT30/TiO2 was about 30%
      of that of PFT30/Al(2)O(3), proving that electron transfer took place between the
      polymer and TiO2. The result that photocatalytic degradation of phenol was almost
      stopped when the solution was saturated with N(2) proved the importance of O(2).
      Addition of NaN(3), an effective quencher of singlet oxygen ((1)O(2)), caused
      about a 40% decrease in the phenol degradation ratio. Addition of alcohols caused
      about a 60% decrease in the phenol photodegradation ratio, indicating that the
      hydroxyl radicals (OH), whose presence was confirmed by electron spin resonance
      (ESR) spectroscopy, was the predominant active species in aqueous solution. In
      anhydrous solution, singlet oxygen ((1)O(2)) was the predominant species. These
      results indicate that oxygen plays a very important role in the photocatalytic
      degradation of phenol.

PMID- 18718712
TI  - Application of biosurfactants and non-ionic surfactants for removal of organic
      matter from metallurgical lead-bearing slime.
AB  - The paper presents evaluation of different extracting solutions used for removal
      of organic matter, especially polycyclic aromatic hydrocarbons (PAHs), from slime
      produced in copper smelting. A series of extraction experiments was conducted
      using biosurfactants and non-ionic surfactant solutions of various
      concentrations. The results showed that the efficiencies of organic matter
      removal by biosurfactants were at the level of 20-30% and depended on the type of
      the used biosurfactant. Biolen Biogrease L, and mixture of alkylobenzenesulfonic
      acid and oxyethylene fatty alcohol were effective for removal of polycyclic
      aromatic hydrocarbons (above 50%), whereas Zymbiose-enz. was ineffective. Non
      ionic surfactants were found to be more effective in removing organic matter than
      biosurfactants. In the case of non-ionic surfactants the removal efficiencies
      depended on the concentration. Increase of Tween 80 concentration caused decrease
      in the efficiency of organic matter removal. The similar results were obtained
      for Nonoxynol 14. By contrast, the increase of Nonoxynol 10 concentration
      resulted in increase of organic matter removal efficiency.

PMID- 18718713
TI  - Ecofriendly biodegradation and detoxification of Reactive Red 2 textile dye by
      newly isolated Pseudomonas sp. SUK1.
AB  - The aim of this work is to evaluate textile dyes degradation by novel bacterial
      strain isolated from the waste disposal sites of local textile industries.
      Detailed taxonomic studies identified the organisms as Pseudomonas species and
      designated as strain Pseudomonas sp. SUK1. The isolate was able to decolorize
      sulfonated azo dye (Reactive Red 2) in a wide range (up to 5 g l(-1)), at
      temperature 30 degrees C, and pH range 6.2-7.5 in static condition. This isolate
      also showed decolorization of the media containing a mixture of dyes.
      Measurements of COD were done at regular intervals to have an idea of
      mineralization, showing 52% reduction in the COD within 24h. Induction in the
      activity of lignin peroxidase and azoreductase was observed during decolorization
      of Reactive Red 2 in the batch culture, which represented their role in
      degradation. The biodegradation was monitored by UV-vis, IR spectroscopy, HPLC.
      The final product, 2-naphthol was characterized by GC-mass spectroscopy. The
      phytotoxicity study revealed the degradation of Reactive Red 2 into non-toxic
      product by Pseudomonas sp. SUK1.

PMID- 18718714
TI  - Biodegradation of p-nitrophenol by Rhodococcus sp. CN6 with high cell surface
      hydrophobicity.
AB  - Rhodococcus sp. CN6, isolated from a pesticide industry's effluent-sediment, was
      able to completely degrade and utilize 100mg/L p-nitrophenol (PNP) as the sole
      carbon, nitrogen and energy sources for growth in the minimal salt media (MSM)
      within 12h. To study the applicability of the strain for bioremediation of PNP,
      its degradation potential was examined in the presence of different supplemented
      carbon and nitrogen sources in MSM with 100mg/L PNP. Dextrin was experienced as
      the best supplemented carbon source used by the strain CN6 during degrading PNP.
      Addition of ammonium nitrate could also increase the PNP degradation rate.
      Preliminary studies on the surface characters of Rhodococcus sp. CN6 were
      undertaken for the sake of exploring its high efficiency on the degradation of
      PNP. Microbial adherence to hydrocarbons (MATH) assays illuminated that the
      strain CN6 was of higher hydrophobicity while grown on higher concentration of
      PNP. The results suggested that the strain CN6 could be used as a potential and
      efficient PNP degrader for the bioremediation of contaminated sites.

PMID- 18718715
TI  - Comparison of synthesis of chelating resin silica-gel-supported
      diethylenetriamine and its removal properties for transition metal ions.
AB  - Four kinds of silica-gel (SG)-supported diethylenetriamine (DETA) chelating
      resins SG-DETA-1, SG-DETA-2, SG-DETA-3, and SG-DETA-4 were prepared by
      functionalization of silica-gel via so-called "heterogeneous-direct-amination"
      (hetero-DA), "homogeneous-direct-amination" (homo-DA), "heterogeneous end-group
      protection" (hetero-EGP), and "homogeneous end-group protection" (homo-EGP)
      routes, respectively. These functionalized reactions on silica-gel were confirmed
      through elemental analysis, infrared spectroscopy, X-ray diffractometry, porous
      analysis, and thermogravimetry. Element analysis revealed that the direct
      amination routes and homogeneous condition were more beneficial than the
      corresponding end-group protection routes and heterogeneous condition to the
      syntheses of chelating resins with high N content. Several metal ions, such as
      Ag(+), Cu(2+), Ni(2+), Hg(2+), Zn(2+) and Pb(2+), were chosen as representatives
      to investigate the relationship between adsorption capacities and N content of
      ligands onto the surface of silica-gel. The experiments results showed that all
      resins, SG-DETA-1, SG-DETA-2, SG-DETA-3 and SG-DETA-4, had a better adsorption
      for Hg(2+) and Cu(2+) than others. One conclusion should be drawn from the above
      compared experiments, that is, higher N content of silica-gel resins does not
      ensure a higher utilization ratio of N.

PMID- 18718716
TI  - Patterns and trends in injuries due to chemicals based on OSHA occupational
      injury and illness statistics.
AB  - The Occupational Safety and Health Administration (OSHA) and the Bureau of Labor
      Statistics (BLS) provide the Survey of Occupational Illness and Injury (SOII)
      statistics from 1992 to 2006, which is often used to measure the rate of injuries
      and illness in industry. The present system of gathering and classifying this
      data was implemented in 1992 with minor changes in 2002. It is hoped that using
      these statistics to measure safety progress and determine patterns of injury will
      guide further improvements in chemical safety. Recognizing such factors as what
      chemicals most frequently cause injury can help to focus safety efforts regarding
      that chemical. Factors such as what part of the body is most commonly affected by
      particular chemicals can lead to improved personnel protection practices. This
      paper provides a detailed analysis of injuries due to chemicals using OSHA's SOII
      data, which offers valuable insight into measures that should be taken to reduce
      injuries due to chemicals.

PMID- 18718717
TI  - Emissions of polychlorinated dibenzo-p-dioxins and dibenzofurans from a heavy oil
      fueled power plant in northern Taiwan.
AB  - We measured the concentrations of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) from the flue gas and the ambient atmosphere of a power
      plant fueled by heavy oil in northern Taiwan. The mean emission concentration and
      I-TEQ concentration of total PCDD/Fs were 0.292 ng/Nm(3) and 0.016 ng I
      TEQ/Nm(3), respectively. All PCDD/F emission concentrations in the flue gas were
      supposed to meet the Environmental Protection Administration Executive Yuan,
      R.O.C. standard (1.0 ng I-TEQ/Nm(3) from 2008). Furthermore, the mean I-TEQ
      concentration in the ambient atmosphere was 0.011 pg I-TEQ/Nm(3), which was much
      lower than the environmental quality standards for dioxins in Japan (0.6 pg
      TEQ/Nm(3)). Also, the PCDD/F emission factor was 0.188 ng I-TEQ/L fuel, which was
      comparable to the data issued in US EPA [EPA, Locating and estimating air
      emissions from sources of dioxins and furans, Office of Air Quality Planning and
      Standards, Research Triangle Park, NC, DCN No. 95-298130-54-01, 1997] (0.2 ng I
      TEQ/L of fuel). Also, the result of the correlations of PCDD/Fs and operational
      parameters illustrated that the positively significant correlation (r=0.502,
      p=0.048) was found only between PCDD/Fs (I-TEQ) and the flue gas emission
      temperature (125-157 degrees C). However, PCDD-TEQ/PCDF-TEQ ratios were
      statistically significantly associated with the decreased flue gas flow (r=
      0.659, p=0.006), moisture (r=-0.612, p=0.012) and flue gas temperature (r=-0.503,
      p=0.047). For proper environmental management of dioxins, it is necessary to
      establish a complete emission inventory of PCDD/Fs, and, in particular, the
      government should pay more attention to power plants to address the information
      shortage.

PMID- 18718719
TI  - Ultrasonic irradiation-induced degradation of low-concentration bisphenol A in
      aqueous solution.
AB  - The treatment of bisphenol A (BPA)-contaminated water has attracted great
      interest recently. In this contribution, ultrasound (US) was applied to remove
      low-concentration BPA in aqueous solution at the frequency of 20 kHz, and the
      effects of ultrasonic intensity and ozone on BPA removal were evaluated for the
      first time. Considering the coexistence of halomethanes and BPA in chlorinated
      drinking water, BPA was degraded under US in the presence of CCl(4). In addition,
      the main intermediates resulting from BPA ultrasonic degradation were identified
      by gas chromatography-mass spectrometry. On the basis of these studies, OH
      radical induced oxidation was identified as the major destruction pathway during
      BPA sonolysis.

PMID- 18718718
TI  - Synthesis and characterization of CuO/Ce 1-x Ti x O2 catalysts used for low
      temperature CO oxidation.
AB  - A series of CuO/Ce(1-x)Ti(x)O(2) catalysts used for low-temperature CO oxidation
      were prepared by impregnation with the support derived from surfactant-assisted
      co-precipitation. The techniques of N(2) adsorption/desorption, X-ray diffraction
      (XRD), X-ray photoelectron spectroscopy (XPS) and temperature-programmed
      reduction by H(2) (H(2)-TPR) were employed for catalyst characterization. It is
      found that the support CeO(2) prepared by the surfactant-assisted method
      possesses much larger specific surface area than the one obtained from
      conventional precipitation. Doping Ti in the support with Ti/Ce atomic ratio of
      1:9 or 3:7 can further increase the surface area of CeO(2) and decrease its
      crystallite size. As a result, the active Cu species possess higher dispersion on
      the support Ce(1-x)Ti(x)O(2) than on pure CeO(2). The strong interaction between
      the dispersed Cu species and the support Ce(1-x)Ti(x)O(2) makes the catalysts
      possess much higher oxidation activity and thermal stability. However, when the
      ratio of Ti/Ce reaches 5:5, opposite effect is found, due to the highest surface
      concentration of Ti and the lack of surface highly dispersed copper species.

PMID- 18718720
TI  - Babesia microti-like rodent parasites isolated from Ixodes persulcatus (Acari:
      Ixodidae) in Heilongjiang Province, China.
AB  - A Babesia microti-like rodent parasite was isolated from the tick, Ixodes
      persulcatus, collected from the northern forest area of Heilongjiang province,
      China. The collected I. persulcatus were allowed to feed on specific pathogen
      free SCID mice and red blood cells from the mice were used to isolate Babesia
      spp. with the microareophilous stationary-phase culture technique. Paired and
      tetrad forms of merozoites were observed by light microscope in red blood cells
      of SCID mice. In vitro growth of the parasites was also achieved in mice
      erythrocytes, which indicated the presence of Babesia spp. in I. persulactus. To
      further identify the Babesia species, polymerase chain reaction screening and
      subsequent sequencing of nuclear small subunit ribosomal RNA (nss-rRNA) was
      employed. The results indicate that the observed parasites might be an isolate
      strain responsible for human babesiosis -B. microti - which has 99.3% identity
      with that of B. microti isolate RcM5201 (AB112050) from Mishan in Heilongjiang
      and Kobe isolates from Japan. In addition, the infection rate of B. microti in I.
      persulcatus ticks in the region was 3.6-4.0% in adult females and no infection in
      males. Though the infection rate is low, the high attack frequency of tick
      species on local residents indicates the risk of human babesiosis in the region
      and the necessity of precautionary measures.

PMID- 18718721
TI  - The postmortem examination of President Kennedy is invalid: the evidence.
AB  - This paper proves that President Kennedy's postmortem examination is a sham. The
      sham nature of the presidential autopsy is based upon several findings
      incompatible with human anatomy, practice of medicine and Newton's second law "an
      object acted upon by a constant force will move with constant acceleration in the
      direction of the force". We review the autopsy report and other assassination
      evidence and demonstrate that the postmortem examination is invalid.

PMID- 18718722
TI  - Acetaminophen: the case for a link to neurodegenerative diseases.

PMID- 18718723
TI  - Hemostatic containment - an evolutionary hypothesis of injury by innate immune
      cells.
AB  - Tissue damage mediated by innate immune cells in reperfusion injury may have a
      survival benefit in infections, preventing sepsis. Tissue damage by leukocytes -
      plugging of small vessels, endothelial cell damage, tissue edema around vessels,
      and stimulation of platelet aggregation - occurs in both reperfusion injury and
      infection-prone wounds. These events create a physical barrier that may sequester
      bacteria, preventing bacterial invasion of the blood. This antisepsis effect,
      termed "hemostatic containment," is triggered by signals that convey
      susceptibility to infection, such as poor blood flow and oxygenation. In active
      and incipient infections, the host accepts some sacrifice of body tissues while
      preventing pathogens from gaining access into sterile sites. This tradeoff
      prevents bacteremia and promotes survival in diseases such as abscesses. Other
      diseases mimic infection-prone states and elicit costly host injury that exceeds
      antibacterial benefits. Mimic diseases include cocaine-induced heart attacks and
      decompression illness. Mimics produce signals that active innate immune cells
      despite the absence of pathogens. Atherosclerotic cardiovascular diseases
      comprise an intermediate, or pseudo-mimic, state characterized by indolent
      pathogens that rarely cause sepsis. Treatment of innate immune cell injury is
      likely to be more effective for mimic and pseudo-mimic states than for infectious
      diseases. Interventions against reperfusion injury might be most effective when
      they improve host immune defenses while eliminating signals of infection risk.

PMID- 18718724
TI  - Impact of glucocorticoids and chronic stress on progression of Parkinson's
      disease.
AB  - Parkinson's disease, a chronic progressive neurodegenerative disorder, has a
      mainly unknown multifactorial etiology. It is characterized by progressive
      degeneration of dopaminergic neurons. Chronic stress, a condition mediated by
      elevated concentrations of glucocorticoids over an extended period of time, has
      been shown to be unfavourable for neurons and to cause damage and neuronal loss
      in certain brain areas. Glucocorticoids are most probably not toxic in a direct
      manner, but can make neuronal damage through several potential indirect
      mechanisms in combination with other destructive factors. We postulate that
      chronic stress will have a harmful effect on patients with Parkinson's disease,
      facilitating neuronal degeneration and accelerating progression of clinical
      manifestations. The damaging impact on neurons will not be because of direct
      cytotoxicity, but by putting them into an energetically unfavourable condition,
      in which they will be more sensitive to destructive factors caused by the primary
      process. Possible mechanisms include elevation of excitatory amino acid
      concentration, which are excitotoxic, disruption of calcium homeostasis,
      metabolic disturbance or impairment of neurogenesis. This could have significant
      implications for patients with Parkinson's disease and chronic stress, or
      patients with glucocorticoid treatment for various immunopathological diseases,
      as well as patients with abnormal secretion of glucocorticoids such as in
      Cushing's syndrome. If confirmed, this hypothesis would represent a valuable
      advancement in care of patients with Parkinson's disease.

PMID- 18718725
TI  - Role of intensity-modulated radiotherapy in reducing toxicity in dose escalation
      for localized prostate cancer.
AB  - PURPOSE: To compare the acute and late gastrointestinal (GI) and genitourinary
      (GU) toxicity in prostate cancer patients treated to a total dose of 78 Gy with
      either a three-conformal radiotherapy technique with a sequential boost (SEQ) or
      a simultaneous integrated boost using intensity-modulated radiotherapy (SIB
      IMRT). PATIENTS AND METHODS: A total of 78 prostate cancer patients participating
      in the randomized Dutch trial comparing 68 Gy and 78 Gy were the subject of this
      analysis. They were all treated at the same institution to a total dose of 78 Gy.
      The median follow-up was 76 and 56 months for the SEQ and SIB-IMRT groups,
      respectively. The primary endpoints were acute and late GI and GU toxicity.
      RESULTS: A significantly lower incidence of acute Grade 2 or greater GI toxicity
      occurred in patients treated with SIB-IMRT compared with SEQ (20% vs. 61%, p =
      0.001). For acute GU toxicity and late GI and GU toxicity, the incidence was
      lower after SIB-IMRT, but these differences were not statistically significant.
      No statistically significant difference were found in the 5-year freedom from
      biochemical failure rate (Phoenix definition) between the two groups (70% for the
      SIB-IMRT group vs. 61% for the SEQ group, p = 0.3). The same was true for the 5
      year freedom from clinical failure rate (90% vs. 72%, p = 0.07). CONCLUSION: The
      results of our study have shown that SIB-IMRT reduced the toxicity without
      compromising the outcome in patients with localized prostate cancer treated to 78
      Gy radiation.

PMID- 18718726
TI  - Study to determine adequate margins in radiotherapy planning for esophageal
      carcinoma by detailing patterns of recurrence after definitive chemoradiotherapy.
AB  - PURPOSE: To ascertain the adequacy of radiotherapy (RT) margins by studying the
      relapse patterns after definitive chemoradiotherapy for carcinoma of the
      esophagus. METHODS AND MATERIALS: We performed a retrospective study assessing
      the first site of disease relapse after definitive chemoradiotherapy that
      included four 3-weekly cycles of cisplatin and continuous infusion 5
      fluorouracil, with conformal RT (50 Gy in 25 fractions) concurrent with Cycles 3
      and 4. The RT planning target volume was the endoscopic ultrasonography/computed
      tomography-defined gross tumor volume with 1.5-cm lateral and 3-cm superoinferior
      margins. RESULTS: A total of 145 patients were included. Their average age was
      65.4 years, 45% had adenocarcinoma, 61% had lower third esophageal tumors, and
      75% had Stage III-IVA disease. After RT, of 142 patients, 85 (60%) had evidence
      of relapse at a median follow-up of 18 months. The relapse was local (within the
      RT field) in 55; distant (metastatic) in 13, and a combination of local and
      distant in 14. The local relapse rates were not influenced by tumor stage, lymph
      node status, or disease length. Three patients developed a relapse in regions
      adjacent to the RT fields; however, it is unlikely that larger field margins
      would have been clinically acceptable or effective in these cases. The median
      overall survival was 15 months. CONCLUSION: The gross tumor volume-planning
      target volume margins in this study appeared adequate. Future efforts to improve
      outcomes using definitive chemoradiotherapy should be directed toward reducing
      the high rates of in-field and distant relapses.

PMID- 18718727
TI  - Validation of the Spanish Addiction Severity Index Multimedia Version (S-ASI-MV).
AB  - This study aimed to develop and test the reliability and validity of a Spanish
      adaptation of the ASI-MV, a computer administered version of the Addiction
      Severity Index, called the S-ASI-MV. Participants were 185 native Spanish
      speaking adult clients from substance abuse treatment facilities serving Spanish
      speaking clients in Florida, New Mexico, California, and Puerto Rico.
      Participants were administered the S-ASI-MV as well as Spanish versions of the
      general health subscale of the SF-36, the work and family unit subscales of the
      Social Adjustment Scale Self-Report, the Michigan Alcohol Screening Test, the
      alcohol and drug subscales of the Personality Assessment Inventory, and the
      Hopkins Symptom Checklist-90. Three-to-five-day test-retest reliability was
      examined along with criterion validity, convergent/discriminant validity, and
      factorial validity. Measurement invariance between the English and Spanish
      versions of the ASI-MV was also examined. The S-ASI-MV demonstrated good test
      retest reliability (ICCs for composite scores between .59 and .93), criterion
      validity (rs for composite scores between .66 and .87), and
      convergent/discriminant validity. Factorial validity and measurement invariance
      were demonstrated. These results compared favorably with those reported for the
      original interviewer version of the ASI and the English version of the ASI-MV.

PMID- 18718728
TI  - Craniometric analysis of the modern Cretan population.
AB  - Despite the fact that sex assessment using craniofacial characteristics is
      commonly made worldwide, a lack of such investigation is noted in the Balkan area
      and in Greece in particular. The aim of this study is to develop a sex
      determination technique using osteometric data from skeletal remains of a
      contemporary Cretan cemetery population. A total of 90 males and 88 females are
      measured according to standard osteometric techniques. Age differences are not
      significant (mean age for men=68.94+/-13.41, N=66; for women=73.21+/-16.77,
      N=66). A total of 16 dimensions taken from the craniofacial skeleton are used and
      data are analyzed using SPSS subroutines. A comparison is made with other
      contemporary populations, including Americans (Terry collection) and South
      Africans (Dart and Pretoria collections), as well as an archaeological sample
      (Middle and Late Helladic) from Crete. Results indicate that males are
      statistically significantly greater than females in all dimensions. Bizygomatic
      breadth is the most discriminatory single dimension and can provide an accuracy
      rate of 82% on average. Using a stepwise method involving five dimensions
      (bizygomatic breadth, cranial length, nasion-prosthion and mastoid height and
      nasal breadth), accuracy is raised to 88.2%. Interestingly, cranial length is
      selected as the first discriminating variable by the stepwise analysis when only
      the neurocranium is available for measurement.

PMID- 18718729
TI  - [Treatment of osteoarticular infections with clindamycin in adults].
AB  - The main characteristics of clindamycin are adequate for treatment of
      osteoarticular infections (OAI): good bone diffusion, broad spectrum of
      antibacterial activity and oral use. METHOD: A number of 61 patients was included
      in an observational retrospective study of efficacy and tolerance. RESULTS:
      Prosthetic infections accounted for 50.8% of the cases and chronic osteitis for
      36.1%. The causative micro-organisms were Staphylococci (72.2%) and Streptococci
      (15.3%); 86.5% of these strains were susceptible to erythromycin, 9.6% were
      erythromycin resistant and susceptible to lincomycin. Clindamycin was associated
      with either ofloxacine, rifampicin, or teicoplanin in 88.5% and the average
      course duration was 101 days. A surgical procedure was performed in 84% of cases.
      Complete cure was obtained in 91.1% at 18 months of follow up. Only one cutaneous
      rash and one Clostridium difficile-associated diarrhea occurred. The other
      adverse effects were gastrointestinal in 36%, cutaneous in 6.6%, and
      hematological in 1.6%, but did not lead to discontinuation of therapy.
      CONCLUSION: Clindamycin can be used in OAI in association with or as an
      alternative to rifampicin, fluoroquinolones, or glycopeptides according to
      microbiological data.

PMID- 18718730
TI  - Molecular and phenotypic characterization of Vibrio aestuarianus subsp.
      francensis subsp. nov., a pathogen of the oyster Crassostrea gigas.
AB  - Eleven Vibrio isolates invading the hemolymph of live and moribund oysters
      (Crassostrea gigas) collected in the field and from a hatchery in France, were
      characterized by a polyphasic approach. Phylogenetic analysis of 16S rRNA, gyrB
      and toxR genes indicated high homogeneity between these strains and the Vibrio
      aestuarianus type strain (ATCC35048(T)), and confirmed previous 16S rRNA
      analysis. In contrast, DNA:DNA hybridization was from 61% to 100%, while
      phenotypic characters and virulence tests showed a large diversity between the
      strains. Nevertheless, several common characters allowed the isolates to be
      distinguished from the reference strain. On the basis of several distinct
      phenotypic characteristics, it is proposed to establish two subspecies within the
      V. aestuarianus spp. group, V. aestuarianus subsp. aestuarianus [D. Tison, R.
      Seidler, Vibrio aestuarianus: a new species from estuarine waters and shellfish,
      Int. J. Syst. Bacteriol. (1983) 699-702] and V. aestuarianus subsp. francensis
      for these French isolates. The characters that differentiate the new strains from
      V. aestuarianus subsp. aestuarianus(T) are virulence (positive for 63% of the
      isolates) and 12:0 fatty acid content. The colonies were smaller and uncoloured,
      whereas no growth occurred at 35 degrees C or on TCBS, and the strains did not
      utilize several substrates, including L-serine, alpha-cyclodextrin, D-mannitol,
      alpha-glycyl-L-aspartic acid, L-threonine and glucose-1-phosphate.

PMID- 18718731
TI  - A rapid method for chemical fingerprint analysis of Hoodia species, related
      genera, and dietary supplements using UPLC-UV-MS.
AB  - Recently, ultra-performance liquid chromatography (UPLC) has proven to be one of
      the most promising developments in the area of high-speed chromatographic
      separations with increased sensitivity and resolution. In this work, a reverse
      phase chromatographic method was developed using UPLC for the chemical
      fingerprint analysis of 12 hoodigosides, related genera and dietary supplements.
      The method is also used for the quantification of P57 in Hoodia species and
      dietary supplements that claim to contain Hoodia. The analysis was performed on a
      Waters Acquity UPLC system with an Acquity UPLC BEH C18 column (100 mm x 2.1mm
      I.D., 1.7 microm) and a gradient elution of water and acetonitrile, both
      containing 0.05% formic acid with a run time of 15 min. The calibration curve of
      P57 showed good linearity (r(2)>0.999) within the established range (1-100
      microg/mL). The limit of detection (LOD) and limit of quantification (LOQ) were
      found to be 0.3 and 0.9 microg/mL, respectively. The RSD for intra- and inter-day
      were less than 3.0%, and the recovery efficiency as 97-103%. LC-mass spectrometry
      coupled with electrospray ionization (ESI) interface method is described for the
      identification of P57. The developed method was successfully applied to the
      identification of 12 oxypregnane glycosides in four different species of Hoodia,
      23 related genera and 35 dietary supplements that claim to contain H. gordonii.
      The UPLC profiles of various plant samples were compared for the presence of
      oxypregnane glycosides. Different sample matrices were successfully analyzed,
      providing the wide range of applicability of this method, including gels,
      capsules, tablets, sprays, tea bags, snack bars, powders and juices.

PMID- 18718732
TI  - Translating research into practice: a German sickness fund supporting patient
      participation.
AB  - OBJECTIVE: To demonstrate how a German sickness fund like the Techniker
      Krankenkasse (TK) tries to translate evidence from research in the field of
      shared decision-making (SDM) into practice. METHODS: This article outlines three
      different initiatives of the TK, supporting patient participation in every day
      life: information tools, continuous interactive case management, and web-based
      interactive patient dialogue. These three activities are supposed to show a
      stepwise development- and introduction-process which is designed to include
      patient feedback at all stages of progress. Wherever available, empirical data is
      added to the description of the initiatives. This data contains information about
      how many people use a special service offered and how useful or satisfying the
      service is in the users' eyes. RESULTS: The examples given show that a single
      sickness fund is able to support patient participation with different kinds of
      initiatives. CONCLUSION: Implementation of SDM will be beneficial for the
      statutory health insurance and will have a positive influence on political and
      professional decision processes. PRACTICE IMPLICATIONS: The TK will continue and
      intensify its engagement for SDM in the future.

PMID- 18718733
TI  - Perceptions of risk in adults with a low or high risk profile of developing type
      2 diabetes; a cross-sectional population-based study.
AB  - OBJECTIVE: To compare the perceived seriousness and risk of type 2 diabetes among
      low risk with high risk profile non-diabetic subjects and examine the
      relationship of perceived risk with multiple self-reported risk indicators.
      METHODS: A cross-sectional population-based study among 4435 low risk profile and
      2607 high risk profile non-diabetic residents of the Hoorn region, participating
      in a stepwise type 2 diabetes screening study. Main outcome measures were
      perceived seriousness and risk of diabetes in subjects categorized (low vs. high
      risk profile) using the Symptom Risk Questionnaire. RESULTS: 85.0% of the low
      risk and 81.2% of the high risk profile subjects perceived diabetes as a moderate
      to very serious disease. About half (43.0%) of all 7042 subjects reported that
      they do not know their risk of having diabetes. The mean perceived risk of having
      diabetes was slightly lower for the low risk compared with the high risk profile
      subjects (difference = 2.8%; 95% confidence interval [CI] = 1.8% to 3.8%; P <
      0.001). This difference was mostly explained by having a parent or sibling with
      diabetes, frequent thirst and claudication (difference = 0.6%; 95% CI = -0.7% to
      1.9%). Interestingly, perceived risk decreased with increasing age within both
      groups (P for trend < 0.001). CONCLUSIONS: Both low risk and high risk profile
      subjects perceive diabetes as a serious disease. Even among those at high risk
      profile for type 2 diabetes, almost half appeared not to know their risk.
      Perceived risk of having diabetes was slightly lower for the low risk compared
      with the high risk profile subjects. Furthermore, perceived risk decreases with
      increasing age. PRACTICE IMPLICATIONS: This study points to a greater need to
      effectively address people's (mis)perceptions, and how to raise the awareness and
      understanding of type 2 diabetes and its risk factors in the general population
      in order to influence early detection and healthy lifestyle changes.

PMID- 18718734
TI  - Developing instruments to measure the quality of decisions: early results for a
      set of symptom-driven decisions.
AB  - OBJECTIVE: To identify a set of critical facts and key goals and concerns for
      five common medical conditions, benign prostate disease, hip and knee
      osteoarthritis, herniated disc and spinal stenosis and examine the validity of
      the method for identifying these items. METHODS: Investigators identified facts
      and goals through literature reviews and qualitative work with patients and
      providers. A cross-sectional survey of patients and providers was conducted to
      examine the accuracy, importance and completeness of the identified items.
      RESULTS: 42 facts (6-16 per condition) and 31 goals and concerns (4-13 per
      condition) were identified. 182 responses were obtained from patients (76.5%
      response rate) and 113 responses from providers (78% response rate). Overall, the
      facts were accurate, important and complete across all conditions. For one
      condition (hip osteoarthritis), the goals did not meet the criteria for
      completeness. There was more disagreement between patients and providers around
      the ranking of goals than of facts. CONCLUSIONS: Overall, respondents found the
      identified facts and goals accurate, important and complete. Significant
      differences between patients' and providers' rankings highlight the importance of
      including both perspectives. PRACTICE IMPLICATIONS: Instruments to measure
      whether or not patients are informed and the extent to which treatments reflect
      patients' goals must balance patients' and providers' perspectives when selecting
      items to include.

PMID- 18718736
TI  - Computational and biological inspired neural networks. Preface.

PMID- 18718735
TI  - Treatment-related symptom clusters in breast cancer: a secondary analysis.
AB  - This study investigated treatment-related symptom clusters and the influence of
      selected demographic/clinical variables on symptom clustering in breast cancer
      patients across a treatment trajectory. A secondary analysis of 282 breast cancer
      patients receiving chemotherapy or radiotherapy was done to determine the
      clustering of oncologic treatment-related symptoms at selected time points of
      treatment. Two distinct clusters were identified: a psychoneurological cluster
      and an upper gastrointestinal cluster. The clustering of symptoms was generally
      stable across the treatment trajectory. The clustering, however, was weaker when
      the time lapse after the completion of treatment became longer. Demographic and
      clinical variables did not significantly influence symptom clustering.
      Psychoneurological symptoms had a tendency to occur together across the treatment
      trajectory, as did upper gastrointestinal symptoms. Effective symptom
      assessment/management strategies need to take into account this co-occurrence of
      symptoms. The findings from this study underscore the need for further
      investigation of the common biological basis of symptoms to attain more effective
      management of multiple symptoms.

PMID- 18718737
TI  - Effect of two carbohydrate-modified tube-feeding formulas on metabolic responses
      in patients with type 2 diabetes.
AB  - OBJECTIVES: This study evaluated the glycemic, insulinemic, and glucagon-like
      peptide-1 (GLP-1) responses of subjects with type 2 diabetes mellitus to
      consumption of two diabetes-specific tube-feeding formulas (slowly digested
      carbohydrate formula [SDC] and diabetes-specific formula [DSF]) and one formula
      intended for individuals without diabetes (standard formula [STND]). METHODS:
      Forty-eight subjects controlled with diet and/or oral antihyperglycemic
      medications received the SDC, DSF, and STND. Postprandial glucose, insulin, and
      GLP-1 were measured on three occasions after an overnight fast in a double
      blinded, randomized, three-treatment, crossover design. RESULTS: The positive
      area under the curve for glucose and insulin with the STND was higher (P < 0.001)
      compared with the SDC and DSF. The adjusted GLP-1 concentration at 60 min was
      higher for the SDC compared with the DSF and STND (P < 0.05). CONCLUSION: Both
      lower-carbohydrate diabetes-specific formulas resulted in a lower postprandial
      blood glucose response compared with the STND. The formula also rich in slowly
      digested carbohydrate and monounsaturated and omega-3 fatty acids (SDC) produced
      significantly lower blood glucose and insulin responses and higher levels of GLP
      1 in the presence of significantly lower insulin concentrations. These results
      support the view that the quantity and quality of carbohydrate and fat may play
      important roles in the management of patients with type 2 diabetes mellitus and
      could result in improved beta-cell function over the long term.

PMID- 18718738
TI  - Microscope versus endoscope in root-end management: a randomized controlled
      study.
AB  - The purpose of this prospective, randomized, clinical study was to monitor the
      outcome of periradicular surgery, in which either a surgical microscope or an
      endoscope was used as a magnification device. A total of 113 teeth in 70 patients
      were included in the study, according to specific selection criteria. The choice
      of endoscope or surgical microscope was made using a randomized table. One
      hundred cases were followed for at least 2 years. Of these, 59 root-end
      management procedures were performed using a microscope and 41 using an
      endoscope. At the 2-year follow-up they were classified into three groups
      (success, uncertain healing and failure) according to radiographic and clinical
      criteria. After a 2-year follow-up, 91 teeth (91%) healed successfully. In the
      group using an endoscope 90% of successful healing was achieved, while 92% of
      success was recorded for the group using a microscope. No statistically
      significant difference was found in the treatment results relating to the type of
      magnification device. The type of magnification device used did not seem to
      affect the outcome of endodontic surgery.

PMID- 18718739
TI  - Temperament and character as schizophrenia-related endophenotypes in non
      psychotic siblings.
AB  - BACKGROUND: Quantitative endophenotypes are needed to better understand the
      pathogenesis of schizophrenia. The psychobiological model of temperament and
      character suggests that personality traits are heritable and regulated by brain
      systems influencing schizophrenia susceptibility. Thus, measures of temperament
      and character may serve as schizophrenia-related endophenotypes in individuals
      with schizophrenia and their non-psychotic siblings. METHODS: Individuals with
      schizophrenia (n=35), their non-psychotic siblings (n=34), controls (n=63), and
      their siblings (n=56) participated in a study of the clinical, neurocognitive and
      neuromorphological characteristics of schizophrenia. A mixed-model approach
      assessed group differences on the Temperament and Character Inventory (TCI).
      Neurocognitive deficits and psychopathology were correlated with the TCI.
      Configurations of TCI domains were examined using a generalized linear model.
      RESULTS: Individuals with schizophrenia and their non-psychotic siblings had
      higher harm avoidance than controls and their siblings. Individuals with
      schizophrenia had lower self-directedness and cooperativeness, and higher self
      transcendence than their non-psychotic siblings, controls, and the siblings of
      controls. Neurocognition was not related to temperament and character in
      individuals with schizophrenia or either control group. In non-psychotic
      siblings, self-directedness and cooperativeness were correlated with working
      memory and crystallized IQ. CONCLUSION: Evidence supports harm avoidance as a
      schizophrenia-related endophenotype. An increased risk of schizophrenia may be
      associated with asociality (configured as high harm avoidance and low reward
      dependence), schizotypy (configured as low self-directedness, low
      cooperativeness, and high self-transcendence), and neurocognitive deficits (poor
      executive functioning, working/episodic memory, attention, and low IQ). The non
      psychotic siblings demonstrated features of a mature character profile including
      strong crystallized IQ, which may confer protection against psychopathology.

PMID- 18718741
TI  - Fluorescence in situ hybridisation (FISH) accelerates identification of Gram
      positive cocci in positive blood cultures.
AB  - Sepsis is a life-threatening disease with a high mortality rate. Rapid
      identification of blood culture isolates plays a crucial role in adequate
      antimicrobial therapy in sepsis patients. To accelerate microbiological
      diagnosis, a comprehensive panel of oligonucleotide probes for fluorescence in
      situ hybridisation (FISH) targeting Gram-positive cocci was compiled and
      evaluated on 428 positive blood culture specimens. By combining genus-specific
      and species-specific probes, the assay allowed discrimination of staphylococci,
      streptococci and enterococci as well as differentiation of therapy-relevant
      pathogens such as Staphylococcus aureus and Enterococcus faecium/durans.
      Furthermore, the newly designed FISH probes STREP2, ENCO and GRANU targeted
      Streptococcus pneumoniae/mitis, Enterococcus spp. (except E. faecalis) and
      Granulicatella adiacens group, respectively. The FISH assay achieved an overall
      sensitivity of 98.65% and a specificity of 99.0% and therefore allowed rapid and
      reliable molecular identification of Gram-positive cocci in blood culture
      specimens.

PMID- 18718740
TI  - Do people with schizophrenia who have objective cognitive impairment identify
      cognitive deficits on a self report measure?
AB  - Individuals diagnosed with schizophrenia spectrum disorders have significant
      neuropsychological deficits that have been linked to poor functional outcome. As
      more treatments are developed and implemented for cognitive impairments, it will
      be important to consider whether people with schizophrenia have insight into the
      neuropsychological symptoms of their illness. Just as insight into psychotic
      symptoms plays a significant role in treatment compliance, it is likely that
      insight into neuro-cognitive dysfunction will be associated with compliance with
      cognitive remediation or cognitive enhancing medications. The objective of this
      study was to evaluate self reported awareness of cognitive deficit in
      schizophrenia using the MIC-SR, a new scale, and to compare self report of
      cognitive deficit with actual neuropsychological performance, and with the MIC-SR
      performance of Healthy Controls. Patients with schizophrenia reported
      significantly more cognitive problems as occurring "Almost Daily" than did
      Healthy Controls. However, Patients were most likely to respond that a cognitive
      problem "Never" occurred, whereas Healthy Controls most often responded "Once a
      Week or Less". The Total Score on the MIC-SR did not prove useful in
      differentiating Healthy Controls from Patients. About one quarter of the
      cognitively impaired patients with schizophrenia showed no awareness of cognitive
      deficit on the MIC-SR. This suggests that clinicians must use self report
      judiciously as an indicator of actual cognitive impairment. The MIC-SR captures a
      range of awareness of cognitive difficulty. The data indicates that there are
      many patients who would benefit from psycho-education about the impact of
      schizophrenia on neuro-cognition.

PMID- 18718742
TI  - Recommendations to achieve rapid therapeutic teicoplanin plasma concentrations in
      adult hospitalised patients treated for sepsis.
AB  - The optimum teicoplanin loading dose and duration of therapy required for rapid
      attainment of a therapeutic trough plasma concentration (C(min)) (> or = 10mg/L
      for serious Gram-positive infections and > or = 20mg/L for deep-seated
      infections) are not known. In this open-label, multicentre, observational study,
      teicoplanin levels were determined following administration of loading doses of 6
      mg/kg every 12h on Day 1 followed by 6 mg/kg once or twice daily to hospitalised
      patients with suspected or diagnosed Gram-positive infections. C(min) levels for
      the first 4 days of treatment were collected 15min prior to drug administration.
      Levels were determined with an Abbott TDx/FLx Analyzer and Seradyn Teicoplanin
      Innofluor Assay Kit. The two target trough values (> or = 10mg/L and > or =
      20mg/L) were only achieved by Day 4 in the once-daily group (n=34; mean 9.55
      mg/L, 95% confidence interval (CI) 8.17-10.94 mg/L) and in the twice-daily group
      (n=40; mean 21.8 mg/L, 95% CI 17.21-26.39 mg/L), respectively. However, the mean
      C(min) in the twice-daily group was > or = 10mg/L (11.03 mg/L) by Day 2. To
      achieve rapid therapeutic C(min) concentrations targeted for the majority of
      serious Gram-positive infections, we recommend teicoplanin loading doses of 6
      mg/kg every 12h for 48h followed by once-daily for infections other than
      infective endocarditis, septic arthritis and osteomyelitis. Regarding the latter
      infections, higher loading doses might be warranted to reach rapid steady-state
      concentrations.

PMID- 18718743
TI  - A potential plasmid-curing agent, 8-epidiosbulbin E acetate, from Dioscorea
      bulbifera L. against multidrug-resistant bacteria.
AB  - Bioassay-guided fractionation of an aqueous methanolic extract of Dioscorea
      bulbifera L. bulbs was performed using organic solvents. A novel plasmid-curing
      compound was identified as 8-epidiosbulbin E acetate (EEA) (norditerpene) on the
      basis of modern spectroscopic analysis and X-ray crystallography. EEA exhibited
      broad-spectrum plasmid-curing activity against multidrug-resistant (MDR)
      bacteria, including vancomycin-resistant enterococci. EEA cured antibiotic
      resistance plasmids (R-plasmids) from clinical isolates of Enterococcus faecalis,
      Escherichia coli, Shigella sonnei and Pseudomonas aeruginosa with 12-48% curing
      efficiency. The reference plasmids of Bacillus subtilis (pUB110), E. coli (RP4),
      P. aeruginosa (RIP64) and Salmonella typhi (R136) were cured with efficiency
      ranging from 16% to 64%. EEA-mediated R-plasmid curing decreased the minimal
      inhibitory concentration of antibiotics against MDR bacteria, thus making
      antibiotic treatment more effective. The antibiotic resistance pattern revealed
      that the compound was effective in the reversal of bacterial resistance to
      various antibiotics. In addition, the compound did not show any cytotoxicity
      against a broad range of human cancer cell lines, namely MCF-7 (breast cancer),
      SiHa (cervical cancer) and A431 (epidermal carcinoma), and hence has the
      potential to be used as a lead compound for drug discovery programmes.

PMID- 18718744
TI  - Epicardial adipose tissue thickness by echocardiography is a marker for the
      presence and severity of coronary artery disease.
AB  - BACKGROUND AND AIM: Epicardial adipose tissue (EAT), which is thought to be a
      component of visceral adiposity, is associated with the metabolic syndrome. We
      aimed to test the hypothesis that echocardiographic EAT thickness can be a marker
      for the presence and severity of coronary artery disease (CAD). METHOD AND
      RESULTS: In all, 150 patients (100 patients with CAD and 50 patients with normal
      coronary arteries by diagnostic coronary angiography; 65 women, 85 men; mean age
      55.7+/-7.4 years) were enrolled. EAT thickness was measured using 2-D
      echocardiographic parasternal long- and short-axis views. EAT thickness
      measurements were compared with angiographic findings. EAT thickness was
      significantly higher in patients with CAD in comparison to those with normal
      coronary arteries (6.9+/-1.5 mm vs. 4.4+/-0.8 mm; P<0.001). Furthermore, EAT
      thickness increased with the severity of CAD (multivessel disease 7.4+/-1.2 mm
      vs. single vessel disease 5.7+/-1.7 mm; P<0.001). Gensini's score significantly
      correlated with EAT thickness (r=0.600, P<0.001). EAT thickness of > or = 5.2 mm
      had 85% sensitivity and 81% specificity (ROC area 0.914, P<0.001, 95% CI [0.86
      0.96]) for predicting CAD. CONCLUSION: EAT thickness, which is easily and non
      invasively evaluated by transthoracic echocardiography, can be an adjunctive
      marker to classical risk factors for the prediction of CAD.

PMID- 18718745
TI  - Serum lipoproteins and cancer.
AB  - BACKGROUND AND AIMS: In haematological and solid tumours the blood lipoprotein
      profile has been reported to be altered; while decreased levels of total
      cholesterol and increased values of triglycerides have been observed. The
      mechanism and meaning of these changes are, however, not fully understood. The
      aim of the present study was to determine relationships between cancer
      progression and serum lipoproteins. METHODS AND RESULTS: We performed a case
      control study. We included cancer patients admitted to the 1st Division of
      Medical Oncology, Businco Hospital of Cagliari, Italy, between 1984 and 1998; 519
      patients with any type of solid tumours and 928 healthy controls. We considered
      total cholesterol (C), high-density lipoprotein (HDL)-C, low-density lipoprotein
      (LDL)-C, triglycerides and apolipoprotein A-1; other parameters examined were
      glycaemia, insulinaemia, body mass index (BMI), homeostasis model assessment
      estimated insulin resistance (HOMA-IR), C reactive protein (CRP) and tumour
      necrosis factor-alpha (TNF-alpha). In the cancer group HDL-C and apolipoprotein A
      1 were lower (p<0.05) and triglycerides were higher (p<0.05) than in controls;
      HDL-C (mg/dl) females: 48 vs. 64; males, 40 vs. 52; Apo-A-1 (mg/dl) females: 125
      vs. 173; males, 120 vs. 152; triglycerides (mg/dl) females: 133 vs. 96; males,
      152 vs. 117. Glucose (mg/dl) was lower in the cancer group (p<0.05); females,
      72.3 vs. 80.0; males, 75.7 vs. 78.4. CONCLUSION: Using multivariate analysis we
      were able to rule out cardiovascular and inflammatory diseases as causes of low
      HDL-C, and also demonstrate that these alterations can be shown as a specific
      consequence of the presence of a malignant tumour with a diagnostic and
      prognostic significance.

PMID- 18718746
TI  - Effect of weight loss through laparoscopic gastric banding on blood pressure,
      plasma renin activity and aldosterone levels in morbid obesity.
AB  - BACKGROUND AND AIMS: Several mechanisms are probably involved in obesity-related
      hypertension. This study was aimed to investigate the effect of significant
      weight loss on blood pressure and plasma renin activity (PRA) and aldosterone
      levels, other then on metabolic profile, in normotensive and hypertensive obese
      subjects. METHODS AND RESULTS: Forty hypertensive and 55 normotensive obese
      subjects were studied under basal conditions and again 1 year after significant
      weight loss obtained through laparoscopic adjustable gastric banding (LAGB).
      Weight, waist circumference, blood glucose, insulin, electrolytes (Na and K),
      lipids and supine and upright PRA and aldosterone were evaluated. All parameters
      evaluated improved, except for total cholesterol, and electrolytes that did not
      change. Blood pressure decreased in hypertensive subjects, with a concordant
      decrease in PRA and supine aldosterone levels, not observed in normotensive
      patients. CONCLUSION: Weight loss is associated with reduction of blood pressure
      and of PRA and aldosterone levels in obese hypertensive subjects.

PMID- 18718747
TI  - An antibody panel for immunohistochemical analysis of the retina in Davidson's
      fixed, paraffin-embedded eyes of rats.
AB  - Unlike most other tissues, the optimal fixative for preserving eye morphology is
      considered to be Davidson's fixative or modified Davidson's rather than formalin.
      However, the methodology for antibodies to be used in tissues fixed this way is
      not normally outlined in current antibody datasheets. Additionally, where eyes
      have been stored in Davidson's fixative, the efficacy of retrospective analysis
      of eye morphology by immunohistochemistry is largely unknown. The aim of this
      study was to compare a panel of six antibodies in both Davidson's-fixed and
      formalin-fixed pigmented and non-pigmented rat eyes, in order to provide optimal
      methods for future retinal immunohistochemical evaluation with image analysis.
      The antibodies evaluated were raised against rhodopsin, synaptophysin, glutamine
      synthetase, glial fibrillary acidic protein (GFAP), cleaved caspase-3 and phospho
      histone H3 (PH3). Overall, the staining quality of these antibodies was found to
      be optimal in Davidson's compared to formalin-fixed tissues after a time period
      of up to 4 days in fixative. The methods outlined thus provide a platform for
      future detailed analysis of retinal pathology in Davidson's-fixed eyes.

PMID- 18718748
TI  - Rapid quantification of periodontitis-related bacteria using a novel modification
      of Invader PLUS technologies.
AB  - The Invader PLUS technology is a sensitive, rapid method for the detection and
      quantification of nucleic acid. While the original technology is based on the
      amplification by polymerase chain reaction (PCR) of the target sequence followed
      by its detection using the Invader technology, the current modification allows
      simultaneous PCR amplification and Invader reaction. The PCR primers and the
      Invader probes are designed to operate at the same temperature. This allows
      simpler design and faster results. This technology has been applied for the
      quantification of six periodontitis-related bacteria (Actinobacillus
      actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia,
      Toreponema denticola, Tannerella forsythensis and Fusobacterium nucleatum).
      Direct comparison of this modified Invader PLUS with real-time PCR demonstrated
      similar linear range. Furthermore, testing of 64 volunteers showed a good
      correlation between both technologies with correlation factors r2 spanning
      between 0.827 and 0.987. We demonstrated here that the proposed improvement of
      the Invader PLUS allows the detection and quantification of DNA sequences using a
      simple design and protocol that can be implemented in clinical testing.

PMID- 18718749
TI  - Influences of chemical activators on incinerator bottom ash.
AB  - This research has applied different chemical activators to mechanically and
      thermally treated fine fraction (<14 mm) of incinerator bottom ash (IBA), in
      order to investigate the influences of chemical activators on this new pozzolanic
      material. IBA has been milled and thermally treated at 800 degrees C (TIBA). The
      TIBA produced was blended with Ca(OH)(2) and evaluated for setting time,
      reactivity and compressive strength after the addition of 0.0565 mole of
      Na(2)SO(4), K(2)SO(4), Na(2)CO(3), K(2)CO(3), NaOH, KOH and CaCl(2) into 100g of
      binder (TIBA+Ca(OH)(2)). The microstructures of activated IBA and hydrated
      samples have been characterized by X-ray diffraction (XRD) and thermogravimetry
      (TG) analysis. Thermal treatment is found to produce gehlenite
      (Ca(2)Al(2)SiO(7)), wollastonite (CaSiO(3)) and mayenite (Ca(12)Al(14)O(33))
      phases. The thermally treated IBA samples are significantly more reactive than
      the milled IBA. The addition of Na(2)CO(3) can increase the compressive strength
      and calcium hydroxide consumption at 28-day curing ages. However, the addition of
      Na(2)SO(4), K(2)SO(4), K(2)CO(3), NaOH and KOH reduces the strength and hydration
      reaction. Moreover, these chemicals produce more porous samples due to increased
      generation of hydrogen gas. The addition of CaCl(2) has a negative effect on the
      hydration of TIBA samples. Calcium aluminium oxide carbonate sulphide hydrate
      (Ca(4)Al(2)O(6)(CO(3))(0.67)(SO(3))(0.33)(H(2)O)(11)) is the main hydration
      product in the samples with activated IBA, except for the sample containing
      CaCl(2).

PMID- 18718750
TI  - What do C&D waste and end-of-life refrigerators have in common?

PMID- 18718751
TI  - One-step co-electropolymerized conducting polymer-protein composite film for
      direct electrochemistry-based biosensors.
AB  - A novel meliorative conducting polymer-redox protein composite film was
      fabricated via one-step co-electropolymerization approach. With electrostatic
      interactions between the conducting polymer and the protein, the composite film
      possesses attractive features, especially in studies of direct electron transfer
      of redox proteins as well as the development of unique protein based biosensors.
      Electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM),
      reflectance absorption infrared spectroscopy (RAIR) and ultraviolet visible
      spectroscopy (UV-vis) were performed to characterize the unique film. The direct
      electron transfer of the redox protein in the composite film were explored, and
      its bioactivity was also investigated by catalyzing the reductions of H(2)O(2)
      and NO(2)(-), demonstrating its great potential applications in direct
      electrochemistry-based high performance biosensors.

PMID- 18718752
TI  - Synergie between molecular imprinted polymer based on solid-phase extraction and
      quartz crystal microbalance technique for 8-OHdG sensing.
AB  - Recently, the 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been used as a marker to
      determine the oxidative stress. There is no any cheap and easy determination
      method based on chips and sensor systems for the determination of 8-OHdG. In this
      study, we have proposed imprinting methods for 8-OHdG recognition and
      determination using methacryloylamidohistidine-platinum(II) [MAH-Pt(II)] as a new
      metal-chelating monomer. The study includes the solid-phase extraction (SPE) of
      blood sample by a new 8-OHdG imprinted sorbent and the measurement of binding
      interaction of 8-OHdG imprinted quartz crystal microbalance (QCM) sensor via
      ligand interaction. 8-OHdG imprinted sorbent has prepared by bulk polymerization
      of MAH-Pt(II) and N-N'-methylenebisacrylamide. 8-OHdG imprinted sensor has
      prepared on a QCM chip coating the thiol pretreated Au electrode. At the end of
      these steps, a thin molecular imprinted polymer (MIP) film for the detection of 8
      OHdG has developed and analytical performance of QCM sensor which has prepared
      using MIP was investigated. The affinity constant (K(a)) for 8-OHdG using MAH-Pt
      based thin film has determined by using the Scatchard method. The average
      percentage recovery of 8-OHdG from plasma samples was found as 80% by using of 8
      OHdG imprinted SPE material. At the last step, 8-OHdG level in several blood
      plasma has been determined by this improved QCM sensor. The obtained results
      confirmed that the 8-OHdG level in cancer patient's blood was significantly
      higher than in general subjects.

PMID- 18718753
TI  - Detection of cadmium by a fiber-optic biosensor based on localized surface
      plasmon resonance.
AB  - A novel transmission-based localized surface plasmon resonance (LSPR) fiber-optic
      probe has been developed to determine the heavy metal cadmium ion (Cd(II))
      concentration. The LSPR sensor was constructed by immobilizing phytochelatins
      (PCs), (gammaGlc-Cys)(8)-Gly, onto gold nanoparticle-modified optical fiber
      (NM(Au)OF). The optimal immobilizing conditions of PCs on to the NM(Au)OF are
      71.6mug/ml PCs in pH 7.4 PBS for 2h. The absorbability (change of light
      absorption) of the PC-functionalized NM(Au)OF sensor increases to 9% upon
      changing the Cd(II) level from 1 to 8ppb with a sensitivity of 1.24ppb(-1) and a
      detection limit of 0.16ppb. The sensor retained 85% of its original activity
      after nine cycles of deactivation and reactivations. In addition, the sensor
      retains its activity and gives reproducible results after storage in 5% d-(+)
      trehalose dehydrate solution at 4 degrees C for 35 days. The dissociation
      constant (K(d)) of the immobilized PCs with Cd(II) was about 6.77x10(-8)M. In
      conclusion, the PCs-functionalized NM(Au)OF sensor can be used to determine the
      concentration of Cd(II) with high sensitivity.

PMID- 18718754
TI  - A comparative evaluation of molecular recognition by monolayers composed of
      synthetic receptors or oriented antibodies.
AB  - Recombinant anti-morphine Fab' fragments have been immobilised on gold by
      covalent attachment through the free thiol groups of the fragment. The antibody
      fragments were intercalated with a non-ionic hydrophilic polymer in order to
      suppress non-specific binding of interfering substances. The antibodies are
      oriented on the surface due to the thiol groups of the antibody and the layer
      shows a high response to antigen. Non-specific binding of bovine serum albumin is
      moreover very low because of the repellent polymer. Synthetic receptors composed
      of an imprinted self-assembled monolayer made from lipoates and the template,
      morphine, exhibit the same binding response to the antigen, morphine as the site
      specific oriented antibody monolayer. A similar binding curve could be obtained
      as that for binding of morphine to an antibody Fab' fragment/polymer layer -
      indicating that synthetic receptors produced are comparable to those of antibody
      layers. Concentrations down to 0.1ng/ml have been measured with surface plasmon
      resonance.

PMID- 18718755
TI  - Role of the tumour necrosis family ligand APRIL in solid tumour development:
      Retrospective studies in bladder, ovarian and head and neck carcinomas.
AB  - A proliferation inducing ligand (APRIL) from the tumour necrosis family (TNF)
      promotes the natural development of solid tumours in pre-clinical models. Here,
      we studied the role of APRIL in patients with urothelial bladder, epithelial
      surface ovarian, and head and neck squamous carcinomas. By using
      immunohistochemistry, we revealed an upregulation of APRIL expression in lesions
      from a significant subset of patients compared to corresponding healthy tissues.
      APRIL upregulation was not due to autocrine production by tumour cells, but
      rather originated from infiltration of APRIL-producing neutrophils. Heparan
      sulphate proteoglycan (HSPG) efficiently concentrated secreted APRIL in lesions.
      Despite this retention, in situ APRIL upregulation did not significantly alter
      disease-free and overall survivals of carcinoma patients in retrospective
      studies. This indicates that APRIL is not potent enough to promote the
      development of solid tumour cells under the pressure of chemotherapy.

PMID- 18718756
TI  - 7-[1H-Indol-2-yl]-2,3-dihydro-isoindol-1-ones as dual Aurora-A/VEGF-R2 kinase
      inhibitors: design, synthesis, and biological activity.
AB  - A novel series of 7-[1H-indol-2-yl]-2,3-dihydro-isoindol-1-ones designed to be
      inhibitors of VEGF-R2 kinase was synthesized and found to potently inhibit VEGF
      R2 and Aurora-A kinases. The structure-based design, synthesis, and initial SAR
      of the series are discussed.

PMID- 18718757
TI  - The C. elegans zonula occludens ortholog cooperates with the cadherin complex to
      recruit actin during morphogenesis.
AB  - The dramatic cell-shape changes necessary to form a multicellular organism
      require cell-cell junctions to be both pliable and strong. The zonula occludens
      (ZO) subfamily of membrane-associated guanylate kinases (MAGUKs) are scaffolding
      molecules thought to regulate cell-cell adhesion [1-3], but there is little known
      about their roles in vivo. To elucidate the functional role of ZO proteins in a
      living embryo, we have characterized the sole C. elegans ZO family member, ZOO-1.
      ZOO-1 localizes with the cadherin-catenin complex during development, and its
      junctional recruitment requires the transmembrane proteins HMR-1/E-cadherin and
      VAB-9/claudin, but surprisingly, not HMP-1/alpha-catenin or HMP-2/beta-catenin.
      zoo-1 knockdown results in lethality during elongation, resulting in the rupture
      of epidermal cell-cell junctions under stress and failure of epidermal sheet
      sealing at the ventral midline. Consistent with a role in recruiting actin to the
      junction in parallel to the cadherin-catenin complex, zoo-1 loss of function
      reduces the dynamic recruitment of actin to junctions and enhances the severity
      of actin filament defects in hypomorphic alleles of hmp-1 and hmp-2. These
      results show that ZOO-1 cooperates with the cadherin-catenin complex to
      dynamically regulate strong junctional anchorage to the actin cytoskeleton during
      morphogenesis.

PMID- 18718758
TI  - The balance between CONSTANS and TEMPRANILLO activities determines FT expression
      to trigger flowering.
AB  - Seasonal changes in day length influence flowering time in many plant species. In
      Arabidopsis, flowering is accelerated by exposure to long day (LD). Those
      inductive photoperiods are perceived in leaves [1] and initiate a long-distance
      signaling mediated by CO and FT. CO is expressed in the phloem according to a
      circadian rhythm [2-4]. Only under LD does CO induce FT expression as high levels
      of CO in the evening coincide with the external light that stabilizes CO protein
      [4, 5]. Subsequently, FT protein travels through the phloem to the shoot apex
      where, together with FD, it initiates flowering [6-12]. Despite the photoperiodic
      induction, a mechanism of floral repression is needed to avoid precocious
      flowering. We show that TEMPRANILLO genes (TEM1 and TEM2) act as novel direct FT
      repressors. Molecular and genetic analyses suggest that a quantitative balance
      between the activator CO and the repressor TEM determines FT levels. Moreover,
      developmental TEM downregulation marks the timing of flowering, as it shifts the
      CO/TEM balance in favor of CO activity, allowing FT transcript to reach the
      threshold level required to trigger flowering. We envision that this might be a
      general mechanism between long-day plants to ensure a tight regulation of
      flowering time.

PMID- 18718760
TI  - Direction of visual apparent motion driven solely by timing of a static sound.
AB  - In temporal ventriloquism, auditory events can illusorily attract perceived
      timing of a visual onset [1-3]. We investigated whether timing of a static sound
      can also influence spatio-temporal processing of visual apparent motion, induced
      here by visual bars alternating between opposite hemifields. Perceived direction
      typically depends on the relative interval in timing between visual left-right
      and right-left flashes (e.g., rightwards motion dominating when left-to-right
      interflash intervals are shortest [4]). In our new multisensory condition,
      interflash intervals were equal, but auditory beeps could slightly lag the right
      flash, yet slightly lead the left flash, or vice versa. This auditory timing
      strongly influenced perceived visual motion direction, despite providing no
      spatial auditory motion signal whatsoever. Moreover, prolonged adaptation to such
      auditorily driven apparent motion produced a robust visual motion aftereffect in
      the opposite direction, when measured in subsequent silence. Control experiments
      argued against accounts in terms of possible auditory grouping, or possible
      attention capture. We suggest that the motion arises because the sounds change
      perceived visual timing, as we separately confirmed. Our results provide a new
      demonstration of multisensory influences on sensory-specific perception [5], with
      timing of a static sound influencing spatio-temporal processing of visual motion
      direction.

PMID- 18718759
TI  - Extracellular matrix rigidity promotes invadopodia activity.
AB  - Invadopodia are actin-rich subcellular protrusions with associated proteases used
      by cancer cells to degrade extracellular matrix (ECM) [1]. Molecular components
      of invadopodia include branched actin-assembly proteins, membrane trafficking
      proteins, signaling proteins, and transmembrane proteinases [1]. Similar
      structures exist in nontransformed cells, such as osteoclasts and dendritic
      cells, but are generally called podosomes and are thought to be more involved in
      cell-matrix adhesion than invadopodia [2-4]. Despite intimate contact with their
      ECM substrates, it is unknown whether physical or chemical ECM signals regulate
      invadopodia function. Here, we report that ECM rigidity directly increases both
      the number and activity of invadopodia. Transduction of ECM-rigidity signals
      depends on the cellular contractile apparatus [5-7], given that inhibition of
      nonmuscle myosin II, myosin light chain kinase, and Rho kinase all abrogate
      invadopodia-associated ECM degradation. Whereas myosin IIA, IIB, and
      phosphorylated myosin light chain do not localize to invadopodia puncta, active
      phosphorylated forms of the mechanosensing proteins p130Cas (Cas) and focal
      adhesion kinase (FAK) are present in actively degrading invadopodia, and the
      levels of phospho-Cas and phospho-FAK in invadopodia are sensitive to myosin
      inhibitors. Overexpression of Cas or FAK further enhances invadopodia activity in
      cells plated on rigid polyacrylamide substrates. Thus, in invasive cells, ECM
      rigidity signals lead to increased matrix-degrading activity at invadopodia, via
      a myosin II-FAK/Cas pathway. These data suggest a potential mechanism, via
      invadopodia, for the reported correlation of tissue density with cancer
      aggressiveness.

PMID- 18718761
TI  - Evidence for an upper limit to mitotic spindle length.
AB  - Size specification of macromolecular assemblies in the cytoplasm is poorly
      understood [1]. In principle, assemblies could scale with cell size or use
      intrinsic mechanisms. For the mitotic spindle, scaling with cell size is
      expected, because the function of this assembly is to physically move sister
      chromatids into the center of nascent daughter cells. Eggs of Xenopus laevis are
      among the largest cells known that cleave completely during cell division. Cell
      length in this organism changes by two orders of magnitude ( approximately 1200
      microm to approximately 12 microm) while it develops from a fertilized egg into a
      tadpole [2]. We wondered whether, and how, mitotic spindle length and morphology
      adapt to function at these different length scales. Here, we show that spindle
      length increases with cell length in small cells, but in very large cells spindle
      length approaches an upper limit of approximately 60 microm. Further evidence for
      an upper limit to spindle length comes from an embryonic extract system that
      recapitulates mitotic spindle assembly in a test tube. We conclude that early
      mitotic spindle length in Xenopus laevis is uncoupled from cell length, reaching
      an upper bound determined by mechanisms that are intrinsic to the spindle.

PMID- 18718762
TI  - Fli1 acts at the top of the transcriptional network driving blood and endothelial
      development.
AB  - Blood and endothelium arise in close association during development, possibly
      from a common precursor, the hemangioblast [1-4]. Genes essential for blood and
      endothelial development contain functional ETS binding sites, and binding and
      expression data implicate the transcription factor, friend leukaemia integration
      1 (Fli1) [5-10]. However, loss-of-function phenotypes in mice, although suffering
      both blood and endothelial defects, have thus far precluded the conclusion that
      Fli1 is essential for these two lineages [11, 12]. By using Xenopus and zebrafish
      embryos, we show that loss of Fli1 function results in a substantial reduction or
      absence of hemangioblasts, revealing an absolute requirement. TUNEL assays show
      that the cells are eventually lost by apoptosis, but only after the regulatory
      circuit has been disrupted by loss of Fli1. In addition, a constitutively active
      form of Fli1 is sufficient to induce expression of key hemangioblast genes, such
      as Scl/Tal1, Lmo2, Gata2, Etsrp, and Flk1. Epistasis assays show that Fli1
      expression is induced by Bmp signaling or Cloche, depending on the hemangioblast
      population, and in both cases Fli1 acts upstream of Gata2, Scl, Lmo2, and Etsrp.
      Taken together, these results place Fli1 at the top of the transcriptional
      regulatory hierarchy for hemangioblast specification in vertebrate embryos.

PMID- 18718763
TI  - Synthesis of new sulfonyl pyrrolidine derivatives as matrix metalloproteinase
      inhibitors.
AB  - A series of new sulfonyl pyrrolidine derivatives was designed, synthesized, and
      assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and
      aminopeptidase N (AP-N). The results showed that these pyrrolidine derivatives
      exhibited highly selective inhibition against MMP-2 as compared with AP-N. The
      compounds 4c, 4j, 5a, and 5b were equally or more potent MMP-2 inhibitors than
      the positive control LY52. The FlexX docking was done to explain the reason for
      the different potency between MMP-2 and AP-N. Structure-activity relationships
      were also briefly discussed.

PMID- 18718764
TI  - The gated electrostatic mass spectrometer (GEMS): definition and preliminary
      results.
AB  - GEMS is a new type of time-of-flight mass spectrometer based on an electrostatic
      energy analyzer. Mass resolution equals the energy analyzer kinetic energy
      resolution, which is set by its slit size. In GEMS, monochromatic ions enter the
      entrance slit at random times, and the gated ion deflection produced by the
      electrostatic field in the analyzer rejects ions that are inside the analyzer at
      gate onset, detecting those entering the analyzer after gate onset. This provides
      mass separation while overcoming the temporal and spatial spread problems typical
      of TOF applications. Paradoxically, GEMS works because all ion masses follow
      identical trajectories. GEMS is easily multiplied into two-dimensional arrays to
      increase sensitivity in space applications, requires relatively low voltages, and
      uses only a few electrical connections. Thus, it is easy to package GEMS as a
      small, low-power instrument for applications in harsh environments. A
      disadvantage of GEMS is that its output is the integral of the TOF spectrum and
      the derivative of the raw data must be taken, a procedure that is likely to add
      noise. A version of GEMS detecting un-deflected ions (u-GEMS) has been tested to
      demonstrate the time-integrated feature of the raw data but without the benefit
      of energy analysis. This paper describes GEMS implemented with the small
      deflection energy analyzer (SDEA), a compact version of the parallel plate energy
      analyzer. SDEA is described both analytically and with ion trajectory simulations
      using the ion trajectory simulation software SIMION; the results are then used to
      describe GEMS and compute its performance.

PMID- 18718765
TI  - The role of anterior deltoid reeducation in patients with massive irreparable
      degenerative rotator cuff tears.
AB  - The management of massive rotator cuff tears in medically unfit, elderly patients
      is difficult. We prospectively assessed 17 patients with radiologically
      confirmed, nontraumatic, massive rotator cuff tears who were treated with an
      anterior deltoid rehabilitation program. All patients were medically unfit, with
      an average age of 80 years (range, 70-96 years). Patients were given standard
      detailed instruction and an illustrated guide. A video recording of shoulder
      motion was made before and after treatment. The Constant score increased from a
      mean of 26 (range, 8-41) before treatment to a mean of 60 (range, 43-77) at a
      minimum of 9 months after treatment. Range of motion in forward elevation
      improved from a mean of 40 degrees (range, 30 degrees -60 degrees ) at
      presentation to a mean of 160 degrees (range 150 degrees -180 degrees ) after the
      deltoid rehabilitation course. We recommend that a structured deltoid
      rehabilitation program is suitable for elderly patients with massive rotator cuff
      tears.

PMID- 18718766
TI  - Repair integrity and clinical outcome after arthroscopic rotator cuff repair
      using single-row anchor fixation: a prospective study of single-tendon and two
      tendon tears.
AB  - This prospective study determined whether single-row anchor fixation would
      reliably improve clinical outcome and maintain structural integrity after
      arthroscopic repair of single-tendon and 2-tendon rotator cuff tears. In 39
      patients, 21 shoulders had single-tendon tears and 18 had 2-tendon tears. Mean
      follow-up was 38 months (minimum, 24 months). A standardized assessment was done
      preoperatively and postoperatively at yearly intervals. Postoperative magnetic
      resonance imaging (MRI) was performed at a minimum 1-year follow-up. Mean forward
      elevation, pain, satisfaction, and American Shoulder and Elbow Surgeons scores
      significantly improved for both groups (P < .01). Postoperative MRI examinations
      showed 19 cuffs (90%) were intact for single-tendon tears and 15 (83%) were
      intact for 2-tendon tears. A recurrent tear on postoperative MRI was
      significantly correlated with the intraoperative finding of asymmetric
      retraction. Arthroscopic rotator cuff repair using single-row anchor fixation
      resulted in significant improvements in clinical outcome and reliable repair
      integrity for both single-tendon and 2-tendon tears.

PMID- 18718767
TI  - The responsiveness of three-dimensional knee accelerations used as an estimation
      of knee instability and loading transmission during gait in osteoarthritis
      patient's follow-up.
AB  - OBJECTIVE: Knee instability and joint loading transmission are two important
      biomechanical factors in subjects with knee osteoarthritis (OA). However, the
      relationship between these factors in a rehabilitation treatment remains unclear.
      The purpose of this study is to determine the responsiveness of a new three
      dimensional (3D) acceleration method used as an estimation of knee instability
      and joint loading transmission during gait in OA subjects after a rehabilitation
      treatment. METHOD: Twenty-four subjects with medial knee OA were included in this
      study. They had clinical and gait evaluations before and after 12 weeks of
      treatment. 3D linear knee accelerations, quadriceps and hamstring isometric
      strength and Western Ontario McMaster Universities Osteoarthritis Index (WOMAC)
      pain were quantified, and compared between both evaluations. Nine asymptomatic
      subjects participated in this study for gait comparison. RESULTS: A significant
      reduction of the anterior posterior (AP) knee acceleration peak (P=0.02) had been
      detected after the treatment. No difference for both distal and lateral knee
      accelerations peak was found. A significant increase in quadriceps (P<0.001) and
      hamstring (P=0.006) strength was seen after treatment. The WOMAC of pain had
      shown significant reduction after the treatment (P<0.001). CONCLUSION: The
      present study demonstrates that the estimation of knee acceleration parameters is
      sensitive to changes in knee OA gait after a rehabilitation treatment. This study
      also indicates that a treatment of 3 months which combines therapeutic and
      exercises program could have benefits on knee OA by increasing AP knee stability
      and stabilize joint loading transmission during gait.

PMID- 18718769
TI  - Reverse foam sclerotherapy of the great saphenous vein with sapheno-femoral
      ligation compared to standard and invagination stripping: a prospective clinical
      series.
AB  - OBJECTIVES: Comparison of Reverse Foam Sclerotherapy of the great saphenous vein
      (GSV) combed with sapheno-femoral junction (SFJ) ligation to standard (Babcock)
      stripping and invagination (Pin) stripping in a prospective clinical series.
      DESIGN: Prospective clinical series. MATERIALS AND METHODS: 90 consecutive limbs
      of 82 patients with incompetence of the GSV resulting in varicose veins were
      prospectively randomised into 3 groups of 30, treated by SFJ ligation and either
      reverse foam sclerotherapy, standard stripping or invagination stripping of the
      GSV. Outcomes were assessed post-operatively and at 2-weeks follow-up. Peri
      operative blood loss (24 hrs), analgesic requirement, bruising and residual
      varicosities were assessed. Bruising was assessed by both patients and
      independent assessors using questionnaires. RESULTS: SFJ ligation plus reverse
      foam sclerotherapy of the GSV was associated with significantly less blood loss,
      bruising and post-op discomfort than either of the stripping techniques.
      (p<0.001, Mann-Whitney) CONCLUSION: Standard stripping of the GSV and
      invagination stripping are not associated with major discomfort and problems in
      the early post-operative period. SFJ ligation and GSV reverse foam sclerotherapy
      yielded greater patient satisfaction with less post-op bruising and discomfort
      and reduced analgesic requirements.

PMID- 18718770
TI  - Traditional versus endoscopic saphenous vein stripping: a prospective randomized
      pilot trial.
AB  - INTRODUCTION: The aim of this pilot study was to compare two methods of removing
      the great saphenous vein (GSV) from the groin to the limit of distal venous
      incompetence. Our aim was to compare endoscopically assisted GSV stripping to
      conventional stripping. DESIGN: Randomised pilot study. PATIENTS AND METHODS: 60
      patients presenting with primary GSV incompetence and symptomatic varicose veins
      were randomly assigned to sapheno-ligation and either conventional GSV stripping
      or endoscopically assisted GSV stripping. The primary endpoint was the number of
      adverse events including haematoma in the thigh, ecchymosis, seroma, wound
      healing complications and wound infections. The SF-36 health survey was completed
      before treatment and one and four weeks postoperatively. The study was approved
      by the local ethics committee (EK 07-041-VK). RESULTS: 60 patients were enrolled
      in the study and randomized to endoscopic (n=30) and to traditional (n=30)
      stripping. The patients age ranged from 30 to 75 years (mean 53 years), 18
      patients were male, 42 female. The combined rate of postoperative morbidity at
      week 1 was 32 events (53%), 13 (42%) events in the endoscopic and 19 (63%) in the
      conventional group (not significant). The SF-36 assessment one week
      postoperatively showed that patients in the endoscopic group reported
      significantly less pain (P=0.03, Mann-Whitney). At four weeks, patients in the
      endoscopic group had significantly less pain (P<0.005) and better physical
      function (P<0.005) and physical role (P=0.01). For all other parameters no
      significant difference noted. CONCLUSION: The results of this study suggest that
      endoscopic GSV excision showed no difference in adverse events between
      treatments, although our pilot study may have been under-powered to demonstrate
      this. The SF-36 assessment suggests more rapid return to normal activities post
      operatively in the endoscopic group.

PMID- 18718768
TI  - Dynamics of neutrophil migration in lymph nodes during infection.
AB  - Although the signals that control neutrophil migration from the blood to sites of
      infection have been well characterized, little is known about their migration
      patterns within lymph nodes or the strategies that neutrophils use to find their
      local sites of action. To address these questions, we used two-photon scanning
      laser microscopy to examine neutrophil migration in intact lymph nodes during
      infection with an intracellular parasite, Toxoplasma gondii. We found that
      neutrophils formed both small, transient and large, persistent swarms via a
      coordinated migration pattern. We provided evidence that cooperative action of
      neutrophils and parasite egress from host cells could trigger swarm formation.
      Neutrophil swarm formation coincided in space and time with the removal of
      macrophages that line the subcapsular sinus of the lymph node. Our data provide
      insights into the cellular mechanisms underlying neutrophil swarming and suggest
      new roles for neutrophils in shaping immune responses.

PMID- 18718771
TI  - Randomised trial of flush saphenofemoral ligation for primary great saphenous
      varicose veins.
AB  - OBJECTIVES: The aim of this study was to assess different techniques of
      saphenofemoral ligation in the treatment of primary varicose veins. METHODS: One
      hundred and eighty-two patients (210 legs) with primary saphenofemoral junction
      incompetence were randomised to standard saphenofemoral ligation (transfixion
      with an absorbable suture) (SSL) or flush saphenofemoral ligation (oversewing
      with 4/0 polypropylene) (FSL). All legs underwent additional great saphenous vein
      stripping and multiple phlebectomies. Patients underwent assessment
      preoperatively, and at 6 weeks, 1 year and 2 years postoperatively with clinical
      examination, duplex imaging and completion of the Aberdeen Varicose Vein Symptom
      Severity Score (AVVSSS). RESULTS: A total of 148 patients (172 legs) attended
      follow-up at 2 years postoperatively. Recurrent varicose veins were visible in 30
      legs (33 per cent) in the SSL group and 26 legs (32 per cent) in the FSL group
      (P=0.90). Neovascularisation was present in 20 groins (22 per cent) in the SSL
      group and 15 groins (19 per cent) in the FSL group (P=0.57). Nine cases of
      neovascularisation in the SSL group and five in the FSL group directly resulted
      in clinical recurrence (P=0.37). CONCLUSIONS: Flush ligation of the
      saphenofemoral junction confers no advantage over standard ligation with respect
      to clinical recurrence and neovascularisation. REGISTRATION NUMBER:
      ISRCTN20235689 (http://www.controlled-trials.com).

PMID- 18718772
TI  - Factors affecting the risk of deep venous occlusion after ultrasound-guided
      sclerotherapy for varicose veins.
AB  - OBJECTIVE: To determine which covariates predisposed to deep venous occlusion
      (DVO) after ultrasound-guided sclerotherapy (UGS) for varicose veins. DESIGN:
      Ultrasound scans before and at 3 to 7 days after UGS to detect post-procedure
      deep venous occlusion. MATERIALS: A consecutive series of 1931 treatment sessions
      in 852 patients treated by a technique for UGS. METHODS: Ultrasound examination
      of the full length of axial deep veins above and below knee before and soon after
      every procedure. Crude chi(2) analysis of all covariates allowed selection of
      those that showed apparent significant influence. Logistic regression analysis of
      these then determined which independently predisposed to post-procedure deep
      venous occlusion. RESULTS: Deep venous occlusion was only observed after UGS
      using foamed sclerosant and occurred following 28 treatment sessions. No
      significant difference for risk of deep venous occlusion was observed for patient
      characteristics or which veins were treated. Logistic regression analysis showed
      significant independent increased risk in a limb from using highly diluted or
      undiluted sclerosant (OR 0.55; 95% CI 0.19 to 1.59 for 0.6-1.0% solution, OR
      10.45; 95% CI 3.12 to 34.99 for 2-2.3% and OR 0.36; 95% CI 0.07 to 1.74 for 3%
      solution), treating veins >or=5mm diameter (OR 3.70; 95% CI 1.23 to 11.13) and
      injecting >or=10 ml of foamed sclerosant for a limb (OR 3.64; 95% CI 1.21 to
      10.90). CONCLUSIONS: The risk of deep venous occlusion after UGS in this series
      was lower when using highly diluted or undiluted sclerosant, when treating veins
      less than 5mm in diameter and when restricting the volume of foam injected to
      less than 10 ml.

PMID- 18718773
TI  - Abdominal aortic aneurysm development in men following a "normal" aortic
      ultrasound scan.
AB  - OBJECTIVES: To determine predictors related to abdominal aortic aneurysm (AAA)
      development following a "normal" aortic ultrasound scan. DESIGN, MATERIALS &
      METHODS: Over a 23-year period, 22 961 men participated in an AAA screening
      programme. Maximum aortic diameter of less than 30 mm was deemed "normal". 4308
      of these "normal" individuals were later re-scanned at intervals for research
      purposes. RESULTS: AAA prevalence was 4.4% at initial scanning. In those with a
      normal scan, 46 patients subsequently presented with AAAs incidentally detected
      and 120 (2.8%) had AAAs identified as part of the ongoing surveillance. The
      median initial aortic size of these 166 men was 25 mm (range 15-29 mm). Over the
      follow-up period, there have been 24 (14%) AAA-related deaths, 24 patients
      underwent successful AAA surgery and 36 died of unrelated causes. In those with
      an initial aortic diameter of <25 mm who later developed an AAA, the odds ratio
      for AAA-related mortality was 2 (95% CI 1-4.1, p=0.03, x(2)). CONCLUSION: AAAs
      can develop following an initial "normal" scan and men with an aortic diameters
      of 25-29 mm appear to be at greater risk. Surveillance for this sub-group may
      further reduce the incidence of undiagnosed AAA and AAA-related mortality.

PMID- 18718774
TI  - MR venography in the detection of pelvic venous congestion.
AB  - PURPOSE: To investigate the feasibility of using magnetic resonance venography
      (MRV) to detect pelvic venous congestion (PVC). METHODS: A prospective study of
      23 female patients with signs and symptoms of PVC, who underwent duplex
      sonography, MRV and phlebography (P). Examinations were interpreted in a blinded
      fashion. Visualization of venous anatomy, presence of venous incompetence and
      congestion grade were evaluated. Sensitivity and specificity of MRV using P as
      reference were calculated. RESULTS: MRV agreed with P in 96% (Cohen-K-value
      0.646) and in 70% (K 0.555) of the cases respectively in the venous anatomy and
      congestion grade. Sensitivity and specificity of MRV were 88% and 67% for ovarian
      veins, 100% and 38% for hypogastric veins and 91% and 42% for the pelvic plexus.
      CONCLUSIONS: In this prospective study MRV showed high sensitivity in the
      evaluation of patients with suspected PVC. Routine use of this diagnostic method
      requires further studies in larger patient cohorts.

PMID- 18718775
TI  - Fracture resistance of endodontically treated teeth with different heights of
      crown ferrule restored with prefabricated carbon fiber post and composite resin
      core by intermittent loading.
AB  - This study evaluated the fracture resistance of endodontically treated teeth
      restored with prefabricated carbon fiber posts and varying quantities of coronal
      dentin. Sixty freshly extracted upper canines were randomly divided into groups
      of 10 teeth each. The specimens were exposed to 250,000 cycles in a controlled
      chewing simulator. All intact specimens were subjected to a static load (N) in a
      universal testing machine at 45 degrees to the long axis. Data were analyzed by 1
      way analysis of variance and Tukey test (alpha = .05). Significant differences (P
      < .001) were found among the mean fracture forces of the test groups (positive
      control, 0 mm,1 mm, 2 mm, 3 mm, and negative control groups: 1022.82 N, 1008.22
      N, 1292.52 N, 1289.19 N, 1255.38 N, and 1582.11, respectively). These results
      suggested that the amount of coronal dentin did not significantly increase the
      fracture resistance of endodontically treated teeth restored with prefabricated
      carbon fiber post and composite resin core.

PMID- 18718776
TI  - Five-year follow-up of a root canal filling material in the maxillary sinus: a
      case report.
AB  - This report describes the 5-year clinical and radiographic follow-up of an
      accidental extrusion of a root canal filling material into the maxillary sinus
      and emphasizes the importance of monitoring of similar cases. The most favorable
      prognosis is achieved by surgically removing the extruded material from the
      sinus. Excess zinc oxide-eugenol-based materials in the sinus might cause
      aspergillosis sinusitis, and this entity often needs many years to develop. In
      this case, endomethasone was the filling material; however, the patient refused
      to undergo any surgical intervention. After a follow-up period of 5 years, the
      patient had no symptoms and radiographic examination disclosed no pathologic
      changes in the antrum.

PMID- 18718777
TI  - Comparison of stability of titanium and absorbable plate and screw fixation for
      mandibular angle fractures.
AB  - OBJECTIVE: The purpose of this experimental study was to compare the stability of
      titanium and absorbable plate and screw fixation systems for mandibular angle
      fractures. STUDY DESIGN: Twenty-one sheep hemimandibles were used to evaluate 3
      different plating techniques. The groups were fixated with a single titanium
      plate, a single absorbable plate and double absorbable plates. A cantilever
      bending biomechanical test model was used for the samples. Each group was tested
      with vertical forces by a servohydraulic testing unit. The displacement values in
      each group at each 10 N stage up to 100 N were compared using the 2-way analysis
      of variance test. RESULTS: The displacement values for the 3 groups differed
      significantly (P < .05). The variance analyses showed that titanium plate
      placement had more favorable biomechanical behavior than others. In addition, the
      2 absorbable plates group had more favorable biomechanical behavior than a single
      absorbable plate group but it was not significantly different at 10 to 40 N.
      CONCLUSION: The study demonstrated that titanium plate and screw fixation system
      had greater resistance to occlusal loads than absorbable plate and screw systems.
      In addition, a second absorbable plate orientation provides a more favorable
      biomechanical behavior than a single absorbable plate placement.

PMID- 18718778
TI  - Is endodontic treatment passe?

PMID- 18718779
TI  - Limitations of the glucose leakage model due to reactivity of glucose with MTA.

PMID- 18718780
TI  - Pilot study: digital subtraction radiography as a tool to assess alveolar bone
      changes in periodontitis patients under treatment with subantimicrobial doses of
      doxycycline.
AB  - BACKGROUND: Subtle changes in marginal alveolar bone level can be demonstrated
      using digital subtraction of sequential radiographs. OBJECTIVE: We aimed to
      evaluate the practical application of geometrically corrected digital subtraction
      in a clinical study of alveolar bone response to a drug previously shown to
      inhibit alveolar bone loss. STUDY DESIGN: Selected periapical radiographs were
      acquired with projective standardization of patients with clinical marginal
      alveolar bone loss. Subsequently, patients received a 6-month regimen of
      subantimicrobial doxycycline or placebo. Standardized radiographs of the same
      alveolar regions were acquired after 3 and 6 months, and baseline radiographs
      were subtracted from these images. RESULTS: Blinded digital subtraction analysis
      indicated various levels of marginal bone gain in 3 of the 6 patients in the
      experimental group, whereas in 3 of the 5 placebo patients the method showed bone
      loss. CONCLUSION: These results suggest that geometrically corrected digital
      subtraction possibly agrees with clinical predictors of bone loss severity.

PMID- 18718781
TI  - Influence of different volumes of EDTA for final rinse on smear layer removal.
AB  - OBJECTIVE: The aim of this study was to analyze the influence of different
      volumes of 17% EDTA for final rinse on smear layer removal on the different areas
      of the root canal. STUDY DESIGN: Forty single-rooted teeth were instrumented
      using rotary instruments. The teeth were divided into 3 test groups according to
      the EDTA volume for final rinse (5 mL, 10 mL, 15 mL) and 1 control group (10 mL
      of 1% sodium hypochlorite). The roots were axially split into halves, and the
      smear layer removal from the canals was determined under scanning electron
      microscope. The data were analyzed using Kruskal Wallis and Dunn tests. RESULTS:
      The 3 experimental groups showed no statistical difference (P > .05); however,
      when the test groups were compared to the control group statistically significant
      differences were found (P < .01). The root canal wall surfaces of teeth in the
      control group showed the presence of heavy smear layer through the entire length
      of the root canals. The other groups showed mainly smear layer-free surfaces or a
      small amount of debris. When coronal, middle and apical thirds were compared,
      there was no statistically significant difference (P > .05). CONCLUSIONS: Based
      on the results, it appears that a final rinse with 5 mL of EDTA per canal
      provides good smear layer removal, with root canal walls free of debris and
      mostly open dentinal tubules in all areas.

PMID- 18718782
TI  - Analysis of factors related to extraction of endodontically treated teeth.
AB  - BACKGROUND: Endodontic therapy is a predictable treatment, resulting in up to 97%
      retention rate for the treated teeth. However, about 3% of endodontically treated
      teeth require further treatment, including extraction of the tooth. STUDY DESIGN:
      This retrospective study analyzed all endodontically treated permanent teeth that
      were extracted in a multidisciplinary clinic in 2006-2007 (n = 547). Associations
      among the extractions' indications and the patients' gender, education, and
      smoking status, as well as tooth type and coronal restoration, were investigated.
      RESULTS: Of the 547 endodontically treated teeth that were subjected to
      extraction, mandibular (44.6%) and maxillary (20.5%) first molars were the most
      common. Fifteen percent of the extracted teeth were restored with a crown,
      whereas 57.4% of the extracted teeth did not have a permanent coronal
      restoration. The reasons for extraction were nonrestorable caries (61.4%),
      endodontic failure (12.1%), vertical root fracture (8.8%), iatrogenic perforation
      (8.8%), periodontal disease (4.6%), unrestorable cusp fracture (2.4%),
      orthodontic (1.3%), and prosthetic (0.2%) considerations and dental trauma
      (0.5%). Periodontitis was more prevalent among current smokers than among
      nonsmokers (P < .05). Gender and education had no influence on the extraction of
      the tooth. Vertical root fracture was more prevalent in mandibular than in
      maxillary first molars (P < .05). Caries was more prevalent in unrestored teeth
      than coronally restored or crowned teeth (P = .001). Endodontic failure and VRF
      were more prevalent in restored than in unrestored teeth (P < .05). CONCLUSIONS:
      The most common extracted tooth profile was the mandibular first molar without
      permanent coronal restoration, which was lost due to caries destruction.
      Endodontically treated teeth were prone to extraction mainly due to nonrestorable
      carious destruction and to a lesser extent to endodontic-related reasons such as
      endodontic failure, VRF, or iatrogenic perforation.

PMID- 18718783
TI  - A comparative study of histologic response to different pulp capping materials
      and a novel endodontic cement.
AB  - OBJECTIVE: The aim of this study was to compare dogs' pulp response to capping
      with calcium hydroxide cement (Dycal), mineral trioxide aggregate (MTA), and a
      novel endodontic cement (NEC). STUDY DESIGN: Twenty-four canine teeth in 6 beagle
      dogs were buccocervically exposed and capped with MTA, Dycal, or NEC. Eight weeks
      later, retrieved samples were observed by optical microscope to grade
      inflammation, formation of dentinal bridge, calcification, necrosis, and presence
      of odontoblast cells. RESULTS: No inflammation was observed in MTA and NEC
      groups, and in 75% of each, dentinal bridge was completely formed. In the Dycal
      group, inflammation and incomplete dentinal bridge were detected in all cases.
      Although MTA and NEC groups had no significant difference between them in each
      measure, the difference between all 3 groups was significant (P < .001).
      CONCLUSION: MTA and NEC showed similar favorable biologic response in pulp cap
      treatment, better than Dycal, especially in inducing the formation of dentinal
      bridge.

PMID- 18718784
TI  - Autotransplantation of a supernumerary incisor as a replacement for fused tooth:
      24-month follow-up.
AB  - This case report describes the technique and 24-month follow-up of
      autotransplantation of a well-shaped, healthy supernumerary maxillary central
      incisor as a replacement for a fused maxillary incisor. Because the alignment of
      the teeth neighboring the fused incisor was not suitable as an abutment for post
      transplantation splinting, a custom palatal splint that took anchorage from
      permanent first molars was fabricated. Following extraction of both teeth, the
      supernumerary incisor was immediately autotransplanted into the extraction site
      of the fused incisor. The autotransplanted tooth was secured to the custom splint
      with acid-etch composite, and the splint was removed 2 weeks later. Closure of
      the apex was observed at 18 months. Both the esthetics and function were restored
      to an ideal level in the absence of postoperative complications, as evidenced by
      24-month clinical and radiographic findings.

PMID- 18718785
TI  - An artificial multilayer perceptron neural network for diagnosis of proximal
      dental caries.
AB  - OBJECTIVE: To evaluate if the application of an artificial intelligence model, a
      multilayer perceptron neural network, improves the radiographic diagnosis of
      proximal caries. STUDY DESIGN: One hundred sixty radiographic images of proximal
      surfaces of extracted human teeth were assessed regarding the presence of caries
      by 25 examiners. Examination of the radiographs was used to feed the neural
      network, and the corresponding teeth were sectioned and assessed under optical
      microscope (gold standard). This gold standard served to teach the neural network
      to diagnose caries on the basis of the radiographic exams. To gauge the network's
      capacity for generalization, i.e., its performance with new cases, data were
      divided into 3 subgroups for training, test, and cross-validation. The area under
      the receiver operating characteristic (ROC) curve allowed comparison of efficacy
      between network and examiner diagnosis. RESULTS: For the best of the 25
      examiners, the ROC curve area was 0.717, whereas network diagnosis achieved an
      ROC curve area of 0.884, indicating a sizeable improvement in proximal caries
      diagnosis. CONCLUSION: Considering all examiners, the diagnostic improvement
      using the neural network was 39.4%.

PMID- 18718786
TI  - Clinical outcome of the endodontic treatment of teeth with apical periodontitis
      using an antimicrobial protocol.
AB  - OBJECTIVE: This study investigated the long-term (1-4 years) outcome of the
      endodontic treatment of teeth with apical periodontitis lesions performed by
      undergraduate students using a defined antimicrobial protocol. STUDY DESIGN:
      Treatment protocol included a crown-down instrumentation technique, apical
      enlargement to predetermined sizes and apical level, irrigation with 2.5% sodium
      hypochlorite, and intracanal medication with calcium hydroxide/camphorated
      paramonochlorophenol (CPMC) paste. The first 100 teeth from patients who returned
      for follow-up were examined. The outcome was assessed based on radiographic and
      clinical criteria as healed (success), healing (uncertain), or not healed
      (failure). RESULTS: Overall results showed that 76% of the teeth healed, 19% were
      healing, and 5% had not healed. Most healed cases (75%) or failed cases (80%)
      were already evident at 2 years. Seven cases took 4 years to heal completely.
      CONCLUSIONS: The low failure rate observed in this study reinforces the
      importance of using an evidence-based antimicrobial strategy during endodontic
      treatment of teeth with apical periodontitis.

PMID- 18718787
TI  - Central mucoepidermoid carcinoma with an atypical radiographic appearance.
AB  - Central mucoepidermoid carcinoma (CMC) is a rare osseous neoplasm occurring most
      often in the fourth to seventh decades of life. Its usual presentation is one of
      a locally destructive radiolucent lesion found primarily in the mandible, in the
      premolar region. No reported case to date has shown a mixed radiolucent
      radiopaque expression of this tumor. The objective of this article is to report
      such a case: a CMC that presented an atypical radiographic appearance of a mixed
      lesion.

PMID- 18718788
TI  - Histopathologic features of oral submucous fibrosis: a study of 35 biopsy
      specimens.
AB  - OBJECTIVES: This study was carried out principally to confirm the diagnosis of
      Oral Submucous Fibrosis, to provide a more detailed description of the
      Histopathological changes occurring in OSMF and to look for and record any new
      finding which might be detected. For this reason only previously untreated cases
      were selected for biopsy. SETTING: Patients reporting at Liaquat University
      Hospital, Dental Out Patient Department, Hyderabad, Sindh, Pakistan. SUBJECTS: 35
      biopsy specimens were obtained from patients presenting with Oral Submucous
      Fibrosis reporting prior to receiving any instructions or management and still
      using areca nut preparations in some form. Patients with overt malignancy were
      not included in this study. MAIN OUTCOME MEASURES: Histopathological analysis was
      carried out to confirm the disease and to evaluate the microscopic features of
      Oral Submucous Fibrosis (OSMF). RESULTS: Diffuse nonspecific chronic inflammation
      with fibrosis was present in all specimens (100%). Classical picture of OSMF was
      found in 20 (57.4%) of specimens while 16 (45.7%) showed Lichenoid reaction as
      well. OSMF with ulceration was present in 14 (40%) specimens.
      Pseudoepitheliomatous hyperplasia was recorded in 9 (25.7%). Dysplastic changes
      were seen in 3 (8.6%) specimens. CONCLUSION: This study gives a detailed account
      of the histological changes along with the frequency of their occurrence and
      describes a new finding of Lichenoid reaction occurring in OSMF.

PMID- 18718790
TI  - The effects of high frequency, low intensity ultrasound therapy on parotid flow
      rates.
AB  - OBJECTIVES: Saliva plays a critical role in maintaining oral health and comfort.
      Development of a single device capable of simulating salivary flow with no taste
      or adverse side effects is desirable. STUDY DESIGN: This clinical investigation
      on 23 healthy volunteers with no dry mouth complaints evaluated the effectiveness
      of ultrasonic therapy in mechanical stimulation of the parotid gland to increase
      saliva flow. Stimulated and unstimulated parotid saliva was collected.
      Differences in mean salivary flow rates and affects of age and ethnicity were
      measured. RESULTS: The mean difference between stimulated and unstimulated saliva
      flow rates was 0.009 mL/min +/- SD = 0.042, t (df = 22) = 1.27 with P = .31.
      There were no significant differences of age (P = .26), gender (P = .38), or
      race/ethnicity (P = .58) for the difference of stimulated and unstimulated
      conditions. CONCLUSIONS: Results indicate that high-frequency low-intensity
      ultrasound therapy is not effective in stimulating salivary flow rates.

PMID- 18718791
TI  - Cell-cycle deregulation induced by three different root canal sealers in vitro.
AB  - The aim of this study was to investigate the effects of 3 root canal sealers on
      the cell cycle of mouse fibroblasts (3T3 cell line). Freshly mixed root canal
      sealers (AH Plus, Endofill, and Sealer 26) were eluted for 24 h using cell
      culture medium. Antiproliferation activity of different eluate dilutions was
      determined by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay.
      Cell cycle was subsequently evaluated by flow cytometry. Differences were tested
      by analysis of variance with Tukey test (P < .05). Results showed that the root
      canal sealers inhibited cell growth in a dose-dependent manner. Antiproliferation
      activity of the root canal sealers was associated with cell-cycle deregulation.
      This event involved cell-cycle arrest in the S/G2/M phases and an increase of the
      sub-G1 population, which are consistent with both cytostatic and cytotoxic
      effects. This information may contribute to a better understanding of the
      toxicity mechanism displayed by root canal sealers currently used in clinical
      practice.

PMID- 18718792
TI  - Rare peripheral odontogenic tumors: report of 5 cases and comprehensive review of
      the literature.
AB  - Peripheral odontogenic tumor (POT) is a rarely encountered lesion. We report 5
      cases of POT including adenomatoid odontogenic tumor (AOT), keratocystic
      odontogenic tumor (KCOT), ameloblastic fibroma (AF), developing odontoma (DO),
      and calcifying cystic odontogenic tumor (CCOT), and also provide a review of
      relevant literature to define the tumor profile. Except for PCCOT with enough
      frequency (>100 cases), PAOT (n = 14), PKCOT (n = 15), PAF (n = 5), and PDO (n =
      7) were scarce in the literature. As to the age distribution, PAOT, PAF, and PDO
      fell within the first 2 decades, whereas PKCOT arose in middle-aged adults. A
      marked female predominance was apparent in PAOT, PKCOT, and PAF. Approximately
      90% of PAOT occurred in the maxilla. PAOT and PDO arose primarily in the incisor
      area, and PKCOT and PAF were typically located in permanent canine/premolar and
      deciduous molar regions, respectively. Although most PAOT and all PKCOT affected
      the buccal gingiva, PDO showed a strong predilection for the lingual aspect. With
      the exception of PKCOT, there was no propensity for recurrence in the above POT.
      At this time, it remains to be determined whether the biologic behavior of PKCOT
      is the same as for KCOT. In view of the reported cases, a true extraosseous
      origin of PAOT and PAF, for the most part, is challenging.

PMID- 18718793
TI  - Effect of a calcium hydroxide-based paste associated to chlorhexidine on RAW
      264.7 macrophage cell line culture.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of a calcium
      hydroxide Ca(OH)(2)-based paste (Calen) associated or not to 0.4% chlorhexidine
      digluconate (CHX) on RAW 264.7 macrophage cell line culture. STUDY DESIGN: The
      cell viability (MTT assay), immunostimulating properties (NO dosage), and anti
      inflammatory properties (NO, TNF-alpha, and IL-1alpha dosage) were evaluated
      after cell exposure to the materials. Data were analyzed statistically by Kruskal
      Wallis test at 5% significance level. RESULTS: There was low immunostimulating
      activity of the Calen paste associated or not to 0.4% CHX in the different
      materials' concentrations evaluated (P > .05). Anti-inflammatory activity with
      inhibition of NO and cytokine (TNF-alpha and IL1-alpha) release was observed only
      with Ca(OH)(2) + CHX at the highest concentration (25 microg/mL). CONCLUSION: As
      the Calen paste associated to 0.4% CHX did not alter cell viability or the
      immunostimulating and anti-inflammatory properties, the addition of CHX brought
      no benefits to the Ca(OH)(2)-based paste with regard to the tested parameters.

PMID- 18718794
TI  - Intraoral superficial angiomyxoma.
AB  - Superficial angiomyxoma is an unusual benign myxoid tumor of the trunk, head and
      neck, extremities, and genitalia. We report the third case of intraoral
      superficial angiomyxoma, which occurred within the buccal mucosa of a 37-year-old
      woman. The symptomless slow-growing mass was present for 2 years. The lobulated,
      paucicellular myxoid tumor showed prominent vascularity, stromal inflammation,
      including neutrophils, and immunopositivity for CD34, vimentin, and muscle
      specific actin. Cure is effected by localized excision, with follow-up, owing to
      the high recurrence rate of the cutaneous tumors, which has not been
      substantiated for the few reported intraoral cases. Superficial angiomyxoma does
      indeed occur intraorally and should be included in the differential diagnosis of
      myxoid intraoral soft tissue neoplasms.

PMID- 18718795
TI  - Condition-specific quality of life in Jordanian patients with dentofacial
      deformities: a comparison of generic and disease-specific measures.
AB  - OBJECTIVES: To determine the impact of dentofacial deformities and related
      treatment on quality of life (QOL) of Jordanian patients, and to make a
      comparison between the generic and specific measures used. STUDY DESIGN: A case
      control study was performed involving 143 subjects: 36 before surgery, 35 after
      orthognathic treatment, 35 who declined surgery (Dec-surg), and 37 control
      subjects. Their QOL was assessed using the 36-item Short-Form Health Survey (SF
      36) and Orthognathic Quality of Life Questionnaire (OQLQ). RESULTS: There were
      significant differences in OQLQ scores among the 4 groups (P < .001). When
      comparing the presurgery group to other groups: significant differences were
      found with postsurgery, Dec-surg, and control subjects (P < .001). The Dec-surg
      group showed no significant differences with postsurgery and control groups.
      CONCLUSIONS: Orthognathic surgery has a positive impact on patients' QOL. The
      condition-specific OQLQ showed better discriminator ability than the generic SF
      36, although both measures provide an effective combination to evaluate QOL in
      patients with dentofacial deformities. More emphasis is required to understand
      emotional and psychosocial status of patients in addition to their esthetic and
      functional needs.

PMID- 18718796
TI  - Observer reliability of three-dimensional cephalometric landmark identification
      on cone-beam computerized tomography.
AB  - OBJECTIVE: To evaluate reliability in 3-dimensional (3D) landmark identification
      using cone-beam computerized tomography (CBCT). STUDY DESIGN: Twelve presurgery
      CBCTs were randomly selected from 159 orthognathic surgery patients. Three
      observers independently repeated 3 times the identification of 30 landmarks in
      the sagittal, coronal, and axial slices. A mixed-effects analysis of variance
      model estimated the intraclass correlations (ICC) and assessed systematic bias.
      RESULTS: The ICC was >0.9 for 86% of intraobserver assessments and 66% of
      interobserver assessments. Only 1% of intraobserver and 3% of interobserver
      coefficients were <0.45. The systematic difference among observers was greater in
      X and Z than in Y dimensions, but the maximum mean difference was quite small.
      CONCLUSION: Overall, the intra- and interobserver reliability was excellent.
      Three-dimensional landmark identification using CBCT can offer consistent and
      reproducible data if a protocol for operator training and calibration is
      followed. This is particularly important for landmarks not easily specified in
      all 3 planes of space.

PMID- 18718797
TI  - Evaluation of the ability of laser Doppler flowmetry for the assessment of pulp
      vitality in general dental practice.
AB  - OBJECTIVES: In this study we investigated pulpal blood flow (PBF) values and
      moving blood cell velocity (MBCV) curves recorded by laser Doppler flowmetry
      (LDF) for pulpal vitality diagnosis in general dental practice and to compare
      MBCV curves to standard diagnostic tests in traumatology. STUDY DESIGN: LDF tests
      performed with the PeriFlux System 5000 were applied to vital and nonvital
      (endodontic treatment) teeth of healthy students (n = 52) and on 24 luxated teeth
      of patients. RESULTS: The PBF values were not reproducible and no statistically
      significant differences were observed between vital and nonvital teeth. MBCV
      curves in contrast could distinguish between the 2 tooth types. Tests on luxated
      teeth showed that while 62.5% of MBCV curves correlated with conventional
      vitality tests, only 12.5% of MBCV curves could help in vital diagnosis.
      CONCLUSION: When applied to luxated teeth, the MBCV curve appeared to be accurate
      when the standard vitality tests indicated a nonvital diagnosis.

PMID- 18718798
TI  - Radiographic endodontic working length estimation: comparison of three digital
      image receptors.
AB  - OBJECTIVE: This in vitro study was conducted to evaluate the accuracy of the
      Schick wireless image receptor compared with 2 other types of digital image
      receptors for measuring the radiographic landmarks pertinent to endodontic
      treatment. STUDY DESIGN: Fourteen human cadaver mandibles with retained molars
      were selected. A fine endodontic file (#10) was introduced into the canal at
      random distances from the apex and at the apex of the tooth; images were made
      with 3 different #2-size image receptors: DenOptix storage phosphor plates,
      Gendex CCD sensor (wired), and Schick CDR sensor (wireless). Six raters viewed
      the images for identification of the radiographic apex of the tooth and the tip
      of a fine (#10) endodontic file. Inter-rater reliability was also assessed.
      RESULTS: Repeated-measures analysis of variance revealed a significant main
      effect for the type of image receptor. Raters' error in identifying structures of
      interest was significantly higher for Denoptix storage phosphor plates, whereas
      the least error was noted with the Schick CDR sensor. A significant interaction
      effect was observed for rater and type of image receptor used, but this effect
      contributed only 6% (P < .01; eta(2) = 0.06) toward the outcome of the results.
      CONCLUSIONS: Schick CDR wireless sensor may be preferable to other solid-state
      sensors, because there is no cable connecting the sensor to the computer. Further
      testing of this sensor for other diagnostic tasks is recommended, as well as
      evaluation of patient acceptance.

PMID- 18718799
TI  - Compound heterozygosity for the Cretan type of non-deletional hereditary
      persistence of fetal hemoglobin and beta-thalassemia or Hb Sabine confirms the
      functional role of the Agamma -158 C>T mutation in gamma-globin gene
      transcription.

PMID- 18718800
TI  - Emerging viral zoonoses: frameworks for spatial and spatiotemporal risk
      assessment and resource planning.
AB  - Spatial epidemiological tools are increasingly being applied to emerging viral
      zoonoses (EVZ), partly because of improving analytical methods and technologies
      for data capture and management, and partly because the demand is growing for
      more objective ways of allocating limited resources in the face of the emerging
      threat posed by these diseases. This review documents applications of
      geographical information systems (GIS), remote sensing (RS) and spatially
      explicit statistical and mathematical models to epidemiological studies of EVZ.
      Landscape epidemiology uses statistical associations between environmental
      variables and diseases to study and predict their spatial distributions.
      Phylogeography augments epidemiological knowledge by studying the evolution of
      viral genetics through space and time. Cluster detection and early warning
      systems assist surveillance and can permit timely interventions. Advanced
      statistical models can accommodate spatial dependence present in epidemiological
      datasets and can permit assessment of uncertainties in disease data and
      predictions. Mathematical models are particularly useful for testing and
      comparing alternative control strategies, whereas spatial decision-support
      systems integrate a variety of spatial epidemiological tools to facilitate
      widespread dissemination and interpretation of disease data. Improved spatial
      data collection systems and greater practical application of spatial
      epidemiological tools should be applied in real-world scenarios.

PMID- 18718801
TI  - Prevalence and predictors of HIV infection among female sex workers in Kaiyuan
      City, Yunnan Province, China.
AB  - BACKGROUND: Sexual transmission is the fastest growing route of HIV transmission
      in China. We undertook this study to describe the risk factors for HIV infection
      in female sex workers (FSWs), and to determine the commercial sex venues where
      FSWs are most at risk of being infected with or infecting others with HIV.
      METHODS: This was a cross-sectional study of 737 FSWs in Kaiyuan City, Yunnan
      Province in southern China, which took place from March to May 2006. RESULTS: The
      overall HIV prevalence was 10.3%, but prevalence varied with sex venue with 25.8%
      of FSWs working on the streets being HIV-positive and none of the FSWs working in
      nightclubs. Adjusted odds ratios (OR) of HIV infection were 9.1 (95% confidence
      interval (CI) 4.67-17.55) for injection drug use, 3.3 (95% CI 1.46-7.37) for non
      injection illegal drug use, 2.7 (95% CI 1.25-5.93) for duration of sex work > or
      = 5 years, 2.2 (95% CI 1.05-4.70) for infection with herpes simplex virus type 2,
      and 2.0 (95% CI 1.12-3.47) for working at a higher risk entertainment venue.
      Although condom use was not a significant risk factor in the overall model, FSWs
      in lower risk venues who reported consistent use with clients had a 70% reduction
      in HIV infections (OR 0.30, 95% CI 0.12-0.90). CONCLUSIONS: Illegal drug use,
      particularly with injection drugs, is the single greatest risk factor for HIV
      infection among FSWs in Kaiyuan City, China. FSWs working on the street or in
      temporary sub-lets, beauty salons, or saunas are at particularly high risk for
      transmitting and being infected with HIV. HIV prevention efforts among FSWs
      should target illegal drug users and these other subgroups.

PMID- 18718802
TI  - [Merkel cell carcinoma, role of radiotherapy and literature review].
AB  - Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin with
      features of epithelial differentiation. It occurs in older patients, appears on
      sun exposed areas and its incidence is increasing. The surgical excision with
      negative margins is the first treatment and adjuvant local irradiation now is
      well established but regional adjuvant (lymph nodes dissection or radiation
      therapy) remains discussed. MCC is chemosensitive but rarely chemocurable in
      patients with metastasis or locally advanced tumors. The most used therapy is
      platinum-based polychemotherapy.

PMID- 18718803
TI  - [Development and regulations of testicular functions in the human foetus].
AB  - Two major functions are assumed by the testis: the production of male gametes
      (that is, spermatozoa) and the production of steroid hormones. Both two functions
      are established during fetal life and are essential to the adult fertility and
      the masculinization of the internal tract and genitalia. For many years, our
      laboratory has been interested in the ontogeny of those two functions in rodents
      and, since 2003, in collaboration with gynecology and obstetrics service of
      professor R. Frydman in Antoine-Beclere hospital, we have studied them in human.
      The first aim of this work was to improve the global knowledge of the human fetal
      testis development by using both our experimental data and the literature. Then,
      we focused on the different defects that can occur during the fetal testis
      development. Indeed, male reproductive abnormalities have been steadily
      increasing since the last decades and are thought to be related to the
      concomitant increase of the concentration of contaminants and particularly of
      endocrine disruptors in the environment. Thus, we decided to study the effect of
      endocrine disruptors on human fetal testis and, more particularly, the effect of
      phthalates, by using an organ culture system developed for human. In contrast to
      the data obtained in rat, mono (ethylhexyl)-phthalate (MEHP), an active
      metabolite of the most widespread phthalate in the environment, does not disturb
      the steroidogenic function. On the other hand, it has a negative effect on the
      male germ cells number. This study is the first experimental demonstration of a
      negative effect of phthalates directly on human fetal testis.

PMID- 18718804
TI  - Evaluation of SCN8A as a candidate gene for autosomal dominant essential tremor.
AB  - OBJECTIVES: Essential tremor (ET) is a common inherited movement disorder whose
      causes remain unknown. The presence of spontaneous tremor in murine mutants may
      provide clues into the pathogenesis of ET. SCN8A encodes the neuronal voltage
      gated sodium channel Na(v)1.6 that is widely expressed in the central nervous
      system. Several mutations of Scn8a in the mouse result in congenital postural
      tremor of the extremities and head. METHODS: We screened SCN8A as a candidate
      gene in a cohort of 95 Caucasian patients with ET and a positive family history,
      including 48 patients with early onset in the first two decades of life. Early
      and adult onset ET subgroups did not differ in disease severity, but early onset
      patients had longer disease duration. Observed sequence variants were also
      screened in an ethnically matched control group. RESULTS: We did not detect SCN8A
      mutations affecting amino acid sequence or splice sites in our cohort of ET
      patients. CONCLUSIONS: Although mutations of Scn8a cause congenital tremor in
      mice, mutations in the sequence of the exons and splice sites of human SCN8A do
      not appear to be a common cause of autosomal dominant essential tremor in
      Caucasian patients.

PMID- 18718805
TI  - A clinical, neuropsychological and olfactory evaluation of a large family with
      LRRK2 mutations.
AB  - We evaluated the neurological and neuropsychological profiles and olfaction as
      presymptomatic markers in a large family with Parkinson disease (PD) caused by
      the G2019S mutation in the LRRK2 gene. Five affected family members, 14
      asymptomatic mutation carriers and 15 non-carriers were compared. Patients had
      typical dopa-responsive PD, frequently associated with cognitive impairment.
      Asymptomatic carriers and non-carriers could not be distinguished because of
      their neuropsychological status, the presence of depression or olfactory
      impairment. We were therefore unable to identify a presymptomatic marker of LRRK2
      related PD.

PMID- 18718806
TI  - Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal
      transitions in epithelial cancers.
AB  - The mechanisms involved in the epithelial to mesenchymal transition (EMT) are
      integrated in concert with master developmental and oncogenic pathways regulating
      in tumor growth, angiogenesis, metastasis, as well as the reprogrammation of
      specific gene repertoires ascribed to both epithelial and mesenchymal cells.
      Consequently, it is not unexpected that EMT has profound impacts on the
      neoplastic progression, patient survival, as well as the resistance of cancers to
      therapeutics (taxol, vincristine, oxaliplatin, EGF-R targeted therapy and
      radiotherapy), independent of the "classical" resistance mechanisms linked to
      genotoxic drugs. New therapeutic combinations using genotoxic agents and/or EMT
      signaling inhibitors are therefore expected to circumvent the chemotherapeutic
      resistance of cancers characterized by transient or sustained EMT signatures.
      Thus, targeting critical orchestrators at the convergence of several EMT
      pathways, such as the transcription pathways NF-kappaB, AKT/mTOR axis, MAPK, beta
      catenin, PKC and the AP-1/SMAD factors provide a realistic strategy to control
      EMT and the progression of human epithelial cancers. Several inhibitors targeting
      these signaling platforms are already tested in preclinical and clinical
      oncology. In addition, upstream EMT signaling pathways induced by receptor and
      nonreceptor tyrosine kinases (e.g. EGF-R, IGF-R, VEGF-R, integrins/FAK, Src) and
      G-protein-coupled receptors (GPCR) constitute practical options under preclinical
      research, clinical trials or are currently used in the clinic for cancer
      treatment: e.g. small molecule inhibitors (Iressa: targeting selectively the EGF
      R; CP-751,871, AMG479, NVP-AEW541, BMS-536924, PQIP, AG1024: IGF-R; AZD2171,
      ZD6474: VEGF-R; AZD0530, BMS-354825, SKI606: Src; BIM-46174: GPCR; rapamycin, CCI
      779, RAD-001: mTOR) and humanized function blocking antibodies (Herceptin: ErbB2;
      Avastin: VEGF-A; Erbitux: EGF-R; Abegrin: alphavbeta3 integrins). We can assume
      that silencing RNA and adenovirus-based gene transfer of therapeutic miR and
      dominant interferring expression vectors targeting EMT pathways and signaling
      elements will bring additional ways for the treatment of epithelial cancers.
      Identification of the factors that initiate, modulate and effectuate EMT
      signatures and their underlying upstream oncogenic pathways should provide the
      basis of more efficient strategies to fight cancer progression as well as genetic
      and epigenetic forms of drug resistance. This goal can be accomplished using
      global screening of human clinical tumors by EMT-associated cDNA, proteome,
      miRome, and tissue arrays.

PMID- 18718807
TI  - A C3-symmetric colorimetric anion sensor bearing hydrazone groups as binding
      sites.
AB  - Tris-hydrazone (1) functioned as a colorimetric chemosensor for a variety of
      anions such as F(-), AcO(-) and H(2)PO(4)(-). The anion binding could be easily
      detected by naked-eye according to color changes. The high binding ability of the
      receptor 1 to anions was further investigated by UV-vis absorption spectroscopy
      in DMSO. The results of job plot of the receptor 1 with different anions
      demonstrated that the stoichiometry of the complex between 1 and F(-) was 1:1
      (1:anion) and the stoichiometry of the other complexes studied was 1:3 (1:anion).

PMID- 18718808
TI  - Details of thermal behavior of spin-coated film of biodegradable poly(3
      hydroxybutyrate-co-3-hydroxyhexanoate) copolymer studied by principal component
      analysis-based two-dimensional (PCA2D) correlation spectroscopy.
AB  - Principal component analysis-based two-dimensional (PCA2D) correlation
      spectroscopy was applied to the temperature-dependent infrared-reflection
      absorption (IRRAS) spectra of a spin-coated film of poly(3-hydroxybutyrate-co-3
      hydroxyhexanoate) (P(HB-co-HHx)) (HHx=7.2 mol%) copolymer. In asynchronous PCA2D
      correlation spectra, we clearly captured the existence of two components in the
      crystalline band of the CO stretching mode, well-ordered primary crystals
      observed at lower wavenumber and less ordered secondary crystals observed at
      higher wavenumber, which is not readily detectable in the original 1D spectra.
      Furthermore, the intensity changes of bands at 1298 and 1280 cm(-1) are
      significantly different in the temperature ranges below and above the transition
      temperature around 140 degrees C identified by the 2D first derivatives plot. The
      result further confirms that the sequence of intensity changes with increasing
      temperature is such that bands for less ordered crystalline components of P(HB-co
      HHx) (HHx=7.2 mol%) are changing first at an earlier (i.e., lower temperature)
      stage.

PMID- 18718809
TI  - Infrared and Raman study of some isonicotinic acid metal(II) halide and
      tetracyanonickelate complexes.
AB  - In this study the M(IN)(2)Ni(CN)(4) [where M: Co, Ni, and Cd, and IN:
      isonicotinic acid, abbreviated to M-Ni-IN] tetracyanonickelate and some metal
      halide complexes with the following stoichiometries: M(IN)(6)X(2) (M: Co; X: Cl
      and Br, and M: Ni; X: Cl, Br and I) and Hg(IN)X(2) (X: Cl, Br, and I) were
      synthesized for the first time. Certain chemical formulas were determined using
      elemental analysis results. The FT-IR and Raman spectra of the metal halide
      complexes were reported in the 4000-0 cm(-1) region. The FT-IR spectra of
      tetracyanonickelate complexes were also reported in the 4000-400 cm(-1) region.
      Vibrational assignments were given for all the observed bands. For a given series
      of isomorphous complexes, the sum of the difference between the values of the
      vibrational modes of the free isonicotinic acid and coordinated ligand was found
      to increase in the order of the second ionization potentials of metals. The
      frequency shifts were also found to be depending on the halogen. The proposed
      structure of tetracyanonickelate complexes consists of polymeric layers of /M
      Ni(CN)(4)/(infinity) with the isonicotinic acid molecules bound directly to the
      metal atom.

PMID- 18718810
TI  - Inter-comparison of 2 microm Heterodyne Differential Absorption Lidar, Laser
      Diode Spectrometer, LICOR NDIR analyzer and flasks measurements of near-ground
      atmospheric CO2 mixing ratio.
AB  - Remote sensing and in situ instruments are presented and compared in the same
      location for accurate CO(2) mixing ratio measurements in the atmosphere: (1) a
      2.064 microm Heterodyne DIfferential Absorption Lidar (HDIAL), (2) a field
      deployable infrared Laser Diode Spectrometer (LDS) using new commercial diode
      laser technology at 2.68 microm, (3) LICOR NDIR analyzer and (4) flasks. LDS,
      LICOR and flasks measurements were made in the same location, LICOR and flasks
      being taken as reference. Horizontal HDIAL measurements of CO(2) absorption using
      aerosol backscatter signal are reported. Using new spectroscopic data in the 2
      microm band and meteorological sensor measurements, a mean CO(2) mixing ratio is
      inferred by the HDIAL in a 1 km long path above the 15m height location of the
      CO(2) in situ sensors. We compare HDIAL and LDS measurements with the LICOR data
      for 30 min of time averaging. The mean standard deviation of the HDIAL and the
      LDS CO(2) mixing ratio results are 3.3 ppm and 0.89 ppm, respectively. The bias
      of the HDIAL and the LDS measurements are -0.54 ppm and -0.99 ppm, respectively.

PMID- 18718811
TI  - Human papillomavirus infection in Barrett's oesophagus in the UK: an infrequent
      event.
AB  - BACKGROUND: Human papillomavirus (HPV) infection has been reported in squamous
      cell carcinomas of the oesophagus and has been recently described in Barrett's
      oesophagus, a premalignant condition which may give rise to oesophageal
      adenocarcinoma. OBJECTIVES: To investigate HPV infection in Barrett's oesophagus
      in a UK population. STUDY DESIGN: DNA was extracted from 73 Barrett's oesophagus
      biopsies and examined for the presence of DNA for 14 high risk (HR) and 6 low
      risk (LR) HPV types. RESULTS: HPV DNA was present in only 1 of 73 samples;
      genotyping indicated this was a high risk type 51 infection. CONCLUSIONS: HPV
      infection appears unlikely to be a significant factor in the aetiology of
      Barrett's oesophagus in the UK.

PMID- 18718812
TI  - A common gene pool for the Neisseria FetA antigen.
AB  - Meningococcal FetA is an iron-regulated, immunogenic outer membrane protein and
      vaccine component. The most diverse region of this protein is a previously
      defined variable region (VR) that has been shown to be immunodominant. In this
      analysis, a total of 275 Neisseria lactamica isolates, collected during studies
      of nasopharyngeal bacterial carriage in infants, were examined for the presence
      of a fetA gene. The fetA VR nucleotide sequence was determined for 217 of these
      isolates, with fetA apparently absent from 58 isolates, the majority of which
      belonged to the ST-624 clonal complex. The VR in N. lactamica was compared to the
      same region in N. meningitidis, N. gonorrhoeae, and a number of other commensal
      Neisseria. Identical fetA variable region sequences were identified among
      commensal and pathogenic Neisseria, suggesting a common gene pool, differing from
      other antigens in this respect. Carriage of commensal Neisseria species, such as
      N. lactamica, that express FetA may be involved in the development of natural
      immunity to meningococcal disease.

PMID- 18718813
TI  - Eosinophilia and coronary artery vasospasm.
AB  - OBJECTIVE: To describe the clinical features, natural history and response to
      treatment of coronary vasospasm associated with eosinophilia. METHODS: Two
      patients with eosinophilia who had recurrent acute coronary events due to multi
      vessel coronary artery spasm are described. The clinical presentation and
      outcomes of these 2 patients and 17 additional cases of eosinophilia and coronary
      artery vasospasm identified on a systematic literature review are presented.
      RESULTS: Patients were usually admitted because of repeated episodes of angina at
      rest and raised plasma markers of myocyte necrosis. Dynamic ST elevation was
      observed in 15 (83%) patients. Coronary angiography was performed in all
      patients. Spontaneous (n=7) or provoked (n=8) coronary artery spasm, which was
      usually multi-focal, was observed in 15 (83%) patients. Symptoms often continued
      despite high dose vasodilators but responded well to prednisone. Recurrent
      coronary events were frequent, and included sudden death (n=4), resuscitated
      cardiac arrest (n=2), myocardial infarction (n=10) and unstable angina (n=11).
      Recurrent events were more frequent when not taking compared to when taking
      prednisone (4.2 versus 0.4 events/year, p=0.002, hazard ratio 11, 95% confidence
      interval 2.4-50). CONCLUSION: Published case reports suggest that coronary
      vasospasm associated with eosinophilia responds poorly to conventional
      vasodilator treatment and the risk of recurrent coronary events is high. Most
      patients respond to treatment which suppresses the eosinophilia.

PMID- 18718814
TI  - Modified blalock-taussig shunt in neonates.

PMID- 18718816
TI  - Patients' experience of home and hospital based cardiac rehabilitation: a focus
      group study.
AB  - BACKGROUND: New cardiac rehabilitation (CR) programmes, such as home programmes
      using the Heart Manual, are being introduced but little is known about patients'
      experiences of these. AIMS: To compare the views of patients who had completed a
      home or hospital-based CR programme and explore the benefits and problems of each
      programme. METHODS: 16 patients from 4 hospital programmes attended one of 3
      focus groups; 10 home programme patients attended one of 2 focus groups. RESULTS:
      Some themes were common to all focus groups: loss of confidence; continuing to
      exercise and lifestyle changes; understanding of heart disease. Hospital
      programme patients particularly enjoyed exercising in a group and mixing with
      other people, and gained motivation and support from others. Home programme
      patients spoke very highly of the Heart Manual and valued the one-to-one support
      of the nurse facilitators. They described the home programme as a lifestyle
      change compared to the hospital programme which they suggested was more like a
      treatment. CONCLUSIONS: Patients in the hospital programme enjoyed the
      camaraderie of group exercise and patients in the home programme valued the
      wealth of information and advice in the Heart Manual and this gave them a feeling
      of being in control of their health.

PMID- 18718818
TI  - Immobilization of glucose oxidase on carbon paper electrodes modified with
      conducting polymer and its application to a glucose fuel cell.
AB  - A carbon paper electrode was modified with the conducting copolymer of 3
      methylthiopene and thiophene-3-acetic acid prepared electrochemically on the
      electrode, and an enzyme electrode was fabricated by covalent immobilization of
      glucose oxidase on the modified electrode. The modification with the conducting
      copolymer increased the surface area of the electrode and the amount of the
      immobilized enzyme. As a result, the enzyme electrode showed a high catalytic
      activity. Moreover, it was found that the increased surface area led to a high
      rate of electron transfer reaction between the electrode and p-benzoquinone
      employed as an electron mediator. The enzyme electrode fabricated with the
      modified carbon paper gave a larger glucose oxidation current than that
      fabricated with the bare one. In addition, the glucose oxidation current was
      found to increase with increasing content of the conducting copolymer in the
      modified carbon paper. Corresponding to the large glucose oxidation current, high
      performance was confirmed for the glucose fuel cell constructed with the enzyme
      electrode based on the modified carbon paper.

PMID- 18718820
TI  - The immediate effect of musculoskeletal physiotherapy techniques and massage on
      pain and ease of breathing in adults with cystic fibrosis.
AB  - The optimal treatment approach to musculoskeletal pain in cystic fibrosis remains
      unclear. This study aimed to examine the effect of a combination of
      musculoskeletal physiotherapy techniques and massage therapy on musculoskeletal
      pain and ease of breathing. A single treatment session was associated with
      reduction in pain and improvement in ease of breathing in adults with cystic
      fibrosis.

PMID- 18718815
TI  - Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early
      stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density
      substudy.
AB  - BACKGROUND: The Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG
      12) bone substudy assesses zoledronic acid for preventing bone loss associated
      with adjuvant endocrine therapy and reports on long-term findings of bone-mineral
      density (BMD) during 3 years of treatment and 2 years after completing adjuvant
      treatment with or without zoledronic acid. The aim of this substudy is to gain
      insight into bone health in this setting. METHODS: ABCSG-12 is a randomised, open
      label, phase III, 4-arm trial comparing tamoxifen (20 mg/day orally) and
      goserelin (3.6 mg subcutaneously every 28 days) versus anastrozole (1 mg/day
      orally) and goserelin (3.6 mg subcutaneously every 28 days), both with or without
      zoledronic acid (4 mg intravenously every 6 months) for 3 years in premenopausal
      women with endocrine-responsive breast cancer. This prospective bone subprotocol
      measured BMD at 0, 6, 12, 36, and 60 months. The primary endpoint of the bone
      substudy (secondary endpoint in the main trial) was change in BMD at 12 months,
      assessed by dual-energy X-ray absorptiometry in assessable patients. Analyses
      were intention to treat. Statistical significance was assessed by t tests. The
      ABCSG-12 trial is registered on the ClinicalTrials.gov website, number
      NCT00295646. FINDINGS: 404 patients were prospectively included in the bone
      substudy and randomly assigned to endocrine therapy alone (goserelin and
      anastrozole or goserelin and tamoxifen; n=199) or endocrine therapy concurrent
      with zoledronic acid (goserelin, anastrozole, and zoledronic acid or goserelin,
      tamoxifen, and zoledronic acid; n=205). After 3 years of treatment, endocrine
      therapy alone caused significant loss of BMD at the lumbar spine (-11.3%, mean
      difference -0.119 g/cm(2) [95% CI -0.146 to -0.091], p<0.0001) and trochanter (
      7.3%, mean difference -0.053 g/cm(2) [-0.076 to -0.030], p<0.0001). In patients
      who did not receive zoledronic acid, anastrozole caused greater BMD loss than
      tamoxifen at 36 months at the lumbar spine (-13.6%, mean difference -0.141
      g/cm(2) [-0.179 to -0.102] vs -9.0%, mean difference -0.095 g/cm(2) [-0.134 to 
      0.057], p<0.0001 for both). 2 years after the completion of treatment (median
      follow-up 60 months [range 15.5-96.6]), patients not receiving zoledronic acid
      still had decreased BMD at both sites compared with baseline (lumbar spine -6.3%,
      mean difference -0.067 g/cm(2) [-0.106 to -0.027], p=0.001; trochanter -4.1%,
      mean difference -0.03 g/cm(2) [-0.062 to 0.001], p=0.058). Patients who received
      zoledronic acid had stable BMD at 36 months (lumbar spine +0.4%, mean difference
      0.004 g/cm(2) [-0.024 to 0.032]; trochanter +0.8%, mean difference 0.006 g/cm(2)
      [-0.018 to 0.028]) and increased BMD at 60 months at both sites (lumbar spine
      +4.0%, mean difference 0.039 g/cm(2) [0.005-0.075], p=0.02; trochanter +3.9%,
      mean difference 0.028 g/cm(2) [0.003-0.058], p=0.07) compared with baseline.
      INTERPRETATION: Goserelin plus tamoxifen or anastrozole for 3 years without
      concomitant zoledronic acid caused significant bone loss. Although there was
      partial recovery 2 years after completing treatment, patients receiving endocrine
      therapy alone did not recover their baseline BMD levels. Concomitant zoledronic
      acid prevented bone loss during therapy and improved BMD at 5 years.

PMID- 18718819
TI  - Pancreatic enzyme replacement therapy for young cystic fibrosis patients.
AB  - Maldigestion in cystic fibrosis (CF) affects approximately 90% of patients. As
      soon as pancreatic insufficiency is identified, enzyme supplementation is
      prescribed even with breast fed infants. A pancreatic enzyme preparation
      developed particularly for infants, Creon for children (CfC), contains smaller
      granules to be administered with a dosing spoon (5000 lipase units per scoop).
      PATIENTS AND METHODS: In a prospective, randomised, multi-centre study, 40
      infants and toddlers received both CfC and Creon 10000 (C10) for two weeks each
      in a cross-over design. Dosing of pancreatic enzymes was continued as applied
      before the study. The primary endpoint was the parents' treatment preference.
      Secondary endpoints included coefficient of fat absorption (CFA), clinical
      symptoms and safety parameters. RESULTS: 20 parents (51%) from the N=39 intent to
      treat sample preferred CfC, 9 (23%) preferred C10, and 10 (26%) had no preference
      The applied doses led to a mean CFA with similar results for both treatments
      (77.8% vs. 78.7%). Gastrointestinal symptoms were reported on a number of study
      days, and some children had abnormal results for laboratory parameters of
      malabsorption. Safety and tolerability of the preparations were good and all
      these parameters were comparable for both treatments. CONCLUSION: Those parents
      who had a preference favoured CfC over C10. Both enzyme preparations improved
      malabsorption to a similar degree, although the applied dosages could have been
      too low in some children reflected in a suboptimal CFA. These data support the
      use of CfC for young patients with cystic fibrosis improving the daily care of
      this cohort detected mainly now through neonatal screening programmes.

PMID- 18718821
TI  - Time course and recovery of arterial blood gases during exacerbations in adults
      with Cystic Fibrosis.
AB  - INTRODUCTION: Hypoxia and hypercapnia are closely linked to morbidity and
      mortality in patients with Cystic Fibrosis (CF). The aims of this study were to
      describe the changes in blood gases during and following an acute pulmonary
      exacerbation in adults with CF. METHODS: We performed a prospective observational
      study of patients with CF admitted for management of an acute exacerbation. Blood
      gas and spirometric analysis was performed on admission, throughout the treatment
      period, and 31 days after discharge (day 45). RESULTS: At presentation, eight of
      nineteen patients had evidence of either hypoxia (PaO(2)<8 kPa) and/or
      hypercapnia (PaCO(2)>6.6 kPa). Blood gas parameters stabilized following two
      weeks of intravenous antibiotic therapy, with little difference evident in
      between treatment completion and subsequent review following discharge.
      Hypercapnia reversed in three patients, with persistent hypercapnia evident in
      two patients. CONCLUSION: In our study group, hypoxemia and hypercapnia were
      frequently observed at presentation of the acute exacerbation. Blood gases
      stabilized following two weeks of intravenous antibiotic therapy, with arterial
      PCO(2) one month following hospital discharge generally similar to that at time
      of discharge.

PMID- 18718822
TI  - Development and validation of a liquid chromatography-tandem mass spectrometry
      method for the determination of xanthinol in human plasma and its application in
      a bioequivalence study of xanthinol nicotinate tablets.
AB  - A sensitive, rapid liquid chromatographic-electrospray ionization mass
      spectrometric method for the determination of xanthinol in human plasma was
      developed and validated. Xanthinol nicotinate in plasma (0.5 mL) was pretreated
      with 20% trichloroacetic acid for protein precipitation. The samples were
      separated using a Lichrospher silica (5 microm, 250 mm x 4.6 mm i.d.). A mobile
      phase of methanol-water containing 0.1% formic acid (50: 50, v/v) was used
      isocratically eluting at a flow rate of 1 mL/min. Xanthinol and its internal
      standard (IS), acyclovir, were measured by electrospray ion source in positive
      selected reaction monitoring mode. The method demonstrated that good linearity
      ranged from 10.27 to 1642.8 ng/mL with r=0.9956. The limit of quantification for
      xanthinol in plasma was 10.27 ng/mL with good accuracy and precision. The mean
      plasma extraction recovery of xanthinol was in the range of 90.9-100.2%. The
      intra- and inter-batch variability values were less than 4.8% and 7.9% (relative
      standard deviation, R.S.D.), respectively. The established method has been
      successfully applied to a bioequivalence study of two xanthinol nicotinate
      tablets for 20 healthy volunteers.

PMID- 18718823
TI  - LC-MS determination and pharmacokinetic study of six phenolic components in rat
      plasma after taking traditional Chinese medicinal-preparation: Guanxinning
      lyophilized powder for injection.
AB  - A traditional Chinese medicinal preparation (TCMP) named Guanxinning lyophilized
      powder for injection composed of Salvia miltiorrhiza Bge. (SMB) and Ligusticum
      chuanxiong Hort. (LCH) was studied. In order to learn the kinetic behaviors of
      the lyophilized powder and provide proofs for rational administration, we have
      developed a sensitive and reproducible method for determination and
      pharmacokinetic study of six main phenolic components {danshensu (DSS),
      protocatechuic acid (PAC), protocatechuic aldehyde (PAL), chlorogenic acid (CHA),
      caffeic acid (CAA) and salvianolic acid B (SAB)} of Guanxinning in rat plasma
      using liquid chromatography-mass spectrometric (LC-MS) method. Sample
      preparations were carried out by protein precipitation with the addition of
      methanol followed by liquid-liquid extraction with ethyl acetate-ethyl ether
      (3:1, v/v) after internal standard (IS, galic acid) spiked. After evaporation to
      dryness, the resultant residue was reconstituted in methanol and injected onto a
      Kromasil C(18) column (150 mm x 4.6 mm i.d. with 5 microm particle size). The
      analytes were analyzed by using negative electrospray ionization (ESI) mass
      spectrometry in selected ion monitoring (SIM) mode. The method was with good
      linearity in the range 0.342-85.0 microgmL(-1) for DSS, 0.0647-12.9 microgmL(-1)
      for PAC, 0.0933-18.7 microgmL(-1) for PAL, 0.0085-3.40 microgmL(-1) for CHA,
      0.0138-2.75 microgmL(-1) for CAA and 0.0272-810 microgmL(-1) for SAB (r>0.99).
      The average extract recoveries of the six analytes from rat plasma were all no
      less than 75%, the precision and accuracy determined were all within the required
      limits. This LC-MS method was successfully applied to pharmacokinetic study of
      the six phenolic components of Guanxinning lyophilized powder for injection in
      rats.

PMID- 18718824
TI  - Chromatographic resolution, characterisation and quantification of VX enantiomers
      in hemolysed swine blood samples.
AB  - The present study was initiated to develop a sensitive and highly selective
      method for the analysis of the enantiomers of the nerve agent VX (O-ethyl S
      [2(diisopropylamino)ethyl] methylphosphonothioate) in blood samples for
      toxicokinetic and therapeutic research. To achieve this goal, analytical and semi
      preparative enantioseparation of VX were carried out with gas and liquid
      chromatography. The GC chiral stationary phase was HYDRODEX-beta-TBDAc (beta
      cyclodextrin), on which VX was baseline-resolved. On the chiral HPLC phase
      CHIRALCEL OD-H the enantiomers of VX were isolated with enantiomeric excess
      >99.99%. They were characterised by specific optical rotation (+/-25.8 deg ml dm(
      1)g(-1) at 20 degrees C and 589 nm) and by determination of cholinesterase
      inhibition rate constants. For the quantitative chiral detection of VX the
      enantioresolution was realized on the HPLC chiral phase CHIRAL AGP. A specific
      procedure was developed to isolate VX from swine blood samples thereby
      stabilising its enantiomers. The limit of detection was 200 fg per enantiomer on
      column. The absolute recovery of the overall sample preparation procedure was
      75%. After an intravenous and percutaneous administration of a supralethal dose
      of VX in anesthetised swine (+)-VX and (-)-VX could be quantified up to 720 min.

PMID- 18718825
TI  - Structure and thermomechanical behavior of NiTiPt shape memory alloy wires.
AB  - The objective of this work is to understand the structure-property relationships
      in polycrystalline NiTiPt (Ti 42.7 at.% Ni 7.5 at %Pt) with a composition showing
      pseudoelasticity at ambient temperatures. Structural characterization of the
      alloy includes grain size determination and texture analysis while the
      thermomechanical properties are explored using tensile testing. Variation in heat
      treatment is used as a vehicle to modify microstructure. The results are compared
      to experiments on Ni-rich NiTi alloy wires (Ti-51.0 at.% Ni), which are in
      commercial use in various biomedical applications. With regards to
      microstructure, both alloys exhibit a <111> fiber texture along the wire drawing
      axis; however, the NiTiPt alloy grain size is smaller than that of the Ni-rich
      NiTi wires, while the latter materials contain second-phase precipitates. Given
      the nanometer-scale grain size in NiTiPt and the dispersed, nanometer-scale
      precipitate size in NiTi, the overall strength and ductility of the alloys are
      essentially identical when given appropriate heat treatments. Property
      differences include a much smaller stress hysteresis and smaller temperature
      dependence of the transformation stress for NiTiPt alloys compared to NiTi
      alloys. Potential benefits and implications for use in vascular stent
      applications are discussed.

PMID- 18718826
TI  - Reconstruction of a huge oral maxillofacial defect caused by necrotic fasciitis
      secondary to leukaemia.
AB  - SUMMARY: An 8-year-old boy who was diagnosed with 'acute non-lymphoblastic
      leukaemia (M2)', contracted secondary oral maxillofacial necrotic fasciitis. The
      wound was cleaned with 3% hypertonic saline, and then covered with iodoform gauze
      every day for about 3 weeks before and after necrotic tissue debridement. The
      local infection was controlled, and plenty of new healthy granular tissue had
      grown. The patient was left with a huge defect including the mouth floor,
      submental area, submandibular area and right cheek when the necrotic tissue was
      removed. Reconstruction of the defect was very difficult because of the patient's
      pre-existing leukaemia condition and severe inflammatory local condition. We
      successfully reconstructed the defect by using the new healthy granular tissue
      and a trapezius myocutaneous flap. During 9 years of follow up, in order to
      improve quality of life, the patient underwent scar modification surgery and
      orthodontic treatment, and facial appearance and oral functions were deemed
      satisfactory.

PMID- 18718827
TI  - Psychological considerations in patient selection for pinnaplasty.

PMID- 18718828
TI  - Use of the slit arteriotomy for end-to-side arterial anastomosis in free-tissue
      transfers to the extremities.
AB  - INTRODUCTION: The purpose of this study was to demonstrate the reliability and
      advantages of the slit arteriotomy for end-to-side arterial anastomosis.
      MATERIALS AND METHODS: Sixty free flaps for reconstruction of the upper and lower
      extremities were re-vascularised using this technique. Flaps used were: gracilis
      (20), latissimus dorsi (18), rectus abdominis (6), lateral arm (6), fibula (3),
      radial forearm (4), scapular (1) and anterolateral thigh (2). TECHNIQUE: A double
      microclamp is applied. Using a 30 degrees microknife, a longitudinal slit is made
      on the recipient vessel. The clamps are then approximated slightly. This slackens
      the segment bearing the slit and opens up the slit to facilitate placement of
      sutures. Beginning at the heel, interrupted sutures are placed in such a way as
      to feed the redundancy of the donor artery wall towards the toe of the
      anastomosis. A slightly oversized slit is used to stretch the donor vessel, which
      due to its inherent elastic recoil keeps the anastomosis patent. Once the
      tourniquet is released, blood flow resumes and the slit forms an elliptical
      opening. A video is available for viewing at our website: www.microflap.com.
      RESULTS: The arterial patency rate was 98%. The mechanical advantage of the slit
      arteriotomy construct was demonstrated through computer simulation on a finite
      element analysis model. CONCLUSION: The slit arteriotomy is simple, reliable, and
      can be consistently used in the transfer of free flaps to the extremities. As no
      portion of the recipient vessel wall is excised, the anastomotic diameter is
      increased. This promotes blood flow through the anastomosis.

PMID- 18718829
TI  - Evaluation of porcine dermal collagen (Permacol) used in abdominal wall
      reconstruction.
AB  - Various methods have been employed to reconstruct complex abdominal wall defects.
      Structural prosthetic materials such as polypropylene mesh and ePTFE (expanded
      polytetrafluoroethylene) have been widely used to close these large fascial
      defects, however, complications with infection and adhesions have led to the
      recent use of more biocompatible implants. Permacol (acellular porcine dermis) is
      used as a dermal scaffold, which eventually becomes vascularised and remodelled
      to reconstruct the abdominal wall in these complex patients. A retrospective
      review was performed of all patients who underwent consecutive abdominal wall
      reconstruction with Permacol at our institution in the year 2006. Twenty-eight
      patients were identified and included in our study. Factors evaluated were: body
      mass index, relevant co-morbidities, aetiology of hernia, hernia defect size
      based on CT scan and intraoperative measurement, size of Permacol implant, length
      of hospital stay, and postoperative complications. Surgical technique was
      standardised among six surgeons and involved a single layer of acellular porcine
      dermis as a subfascial 'underlay' graft under moderate tension upon maximal
      hernia reduction. Tissue expanders were not required for skin closure. Out of 28
      patients, 12 were male and 16 were female. Mean intraoperative hernia size was
      150 cm(2) (range of 10 cm(2) to 600 cm(2)). Mean age was 55 years with an average
      body mass index (BMI) of 34 (largest BMI of 61.4). Defects were attributed to
      either a previous laparotomy incision or open abdomen. Mean hospital stay was
      9.67 days. At a mean follow-up of sixteen months, there were three recurrent
      hernias (10.7%) based on physical examination and postoperative CT scan
      evaluation. One patient developed a superficial wound dehiscence which was
      successfully treated with local wound care and one patient developed a cellulitis
      which was successfully treated with antibiotic therapy. Four patients (14.3%)
      developed a chronic, non-infected fluid collection lasting >one month all of
      which resolved. No patient required removal of the implant due to infection.
      Permacol can be successfully used in the reconstruction of both small and large
      ventral hernias. This biodegradable matrix serves as a safe and useful
      alternative to both synthetic mesh and AlloDerm.

PMID- 18718830
TI  - A case of cortical reorganisation demonstrated by means of functional MRI in a
      patient with a severe form of a complex regional pain syndrome.

PMID- 18718831
TI  - The use of test skin grafting in pemphigus vegetans.

PMID- 18718832
TI  - A prospective randomized control trial comparing one monofilament absorbable
      suture to a braided absorbable suture in children.

PMID- 18718833
TI  - A simple technique to make breast implant capsulectomy easier.

PMID- 18718834
TI  - Simultaneous surgical treatment of ulcer terebrans with intracranial propagation
      and acoustic neurinoma on the same side: a case report.
AB  - This article presents a successful surgical treatment of the patient with
      aggressive basal cell carcinoma with intracranial propagation (ulcer terebrans)
      and simultaneous acoustic neurinoma on the same side.

PMID- 18718835
TI  - A useful and simple tool for the design of abdominoplasty operations: a bendable
      wire.

PMID- 18718836
TI  - Use of composite anterolateral thigh flap as double-vascularised layers for
      reconstruction of complex hand dorsum defect.

PMID- 18718837
TI  - Treatment of large ischial ulcers communicating with the hip joint with proximal
      femoral resection and reconstruction with a combined vastus lateralis, vastus
      intermedius and rectus femoris musculocutaneous flap.
AB  - Pressure ulcers which communicate with the hip joint are very difficult to treat.
      Often, the hip joint is infected with osteomyelitis of the proximal femur
      resulting in bouts of sepsis and flap failure. These patients require proximal
      femoral resection and wide debridement in order to eradicate the infection, which
      in turn results in large and deep cavities. Reconstruction requires either a
      muscle flap or even a total thigh flap if the defect is very large and the pelvis
      is involved. In a series of six ischial or ischio-trochanteric pressure sores
      communicating with the hip joint, following multiple serial debridements, the
      vastus lateralis, vastus intermedius and rectus femoris muscles were raised as a
      single musculocutaneous flap ('three muscle flap'), based on the descending
      branch of the lateral femoral circumflex artery, and transposed into the defect.
      All patients were paraplegics and had signs of sepsis during admission. Two
      patients had prior failed reconstructions within 3 months of admission and the
      others had not been operated on before. The external skin defect of the ulcers
      ranged from 7 x 5 cm to 30 x 12 cm. After 12 months follow up there was no
      recurrence of pressure sores or sepsis. The 'three muscle flap' offers the
      advantage of providing large bulk to fill deep cavities, while preserving the
      rest of the thigh. The flap elevation is fast and safe and the vascular pedicle
      is reliable. This technique is not for simple pressure sores, but should be
      reserved for large pressure sores complicated with large cavities created after
      resection of the proximal femur.

PMID- 18718838
TI  - Neutralizing host responses in hepatitis C virus infection target viral entry at
      postbinding steps and membrane fusion.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) is a leading cause of chronic
      hepatitis worldwide. Viral attachment and entry, representing the first steps of
      virus-host cell interactions, are major targets of adaptive host cell defenses.
      The mechanisms of antibody-mediated neutralization by host neutralizing responses
      in HCV infection are only poorly understood. Retroviral HCV pseudotypes (HCVpp)
      and recombinant cell culture-derived HCV (HCVcc) have been successfully used to
      study viral entry and antibody-mediated neutralization. METHODS: In this study,
      we used these model systems to investigate the mechanism of antibody-mediated
      neutralization by monoclonal antienvelope antibodies and polyclonal anti-HCV
      immunoglobulins purified from HCV-infected patients. RESULTS: Using a panel of
      monoclonal antienvelope antibodies, we identified an epitope within the E1
      glycoprotein targeted by human neutralizing antibodies during postbinding events.
      Interestingly, we observed that host neutralizing responses in the majority of
      HCV-infected individuals include antibodies targeting HCV entry after binding of
      the virus to the target cell membrane. Using a kinetic assay based on HCVpp and
      HCVcc entry, we demonstrate that purified antiviral immunoglobulins derived from
      individual HCV-infected patients appear to inhibit HCV infection at an entry step
      closely linked to CD81 and scavenger receptor BI (SR-BI). CONCLUSIONS: Our
      results indicate that host neutralizing responses in HCV-infected patients target
      viral entry after HCV binding most likely related to HCV-CD81, and HCV-SR-BI
      interactions, as well as membrane fusion. These findings have implications not
      only for the understanding of the pathogenesis of HCV infection but also for the
      design of novel immunotherapeutic and preventive strategies.

PMID- 18718839
TI  - Two populations of ovine bone marrow-derived dendritic cells can be generated
      with recombinant GM-CSF and separated on CD11b expression.
AB  - Whereas studies on dendritic cells in rodents rely largely on bone marrow-derived
      dendritic cells (BM-DCs), no data are available about BM-DCs in sheep, a species
      that is largely used for immunology and transplantation studies. We have
      developed a culture protocol to produce ovine BM-DCs, using 6x(His)-tagged
      recombinant GM-CSF which was purified from baculovirus-infected insect cells.
      When ovine bone marrow progenitors were cultured in the presence of recombinant
      GM-CSF, large numbers of CD11c-positive cells were generated after 6-7 days. The
      phenotypic appearance of BM-DCs was assessed by flow cytometry and electron
      microscopy. Two DC subsets were identified that expressed different levels of MHC
      class II molecules, differed in receptor-mediated endocytosis, and could be
      separated on CD11b expression. When separated cells were incubated with microbial
      products, they react differently to those that are considered the TLR2 and TLR4
      agonists in other species. Indeed, although CD11b(int/hi) cells were partially
      resistant to maturation induced by lipoteichoic acid or lipopolysaccharide, MHC
      class II upregulation was observed on CD11b(dull) cells. Moreover, these cells
      had strong stimulatory capacity for CD4 T cells when assayed in allogeneic
      reactions. This protocol will help analyzing ovine DC interactions with
      pathogens, and enables future studies on the development of vaccines.

PMID- 18718840
TI  - Improved methods for immunohistochemical detection of BrdU in hard tissue.
AB  - Bromodeoxyuridine (BrdU) is used to label synthesizing DNA and to chase label
      retaining cell (LRC). As stem cells divide slowly in adult tissues, they can be
      visualized as LRCs. In order to identify LRCs in hard tissue, we examined optimal
      conditions of fixation, demineralization, and DNA denaturation/antigen retrieval
      for immunohistochemistry of BrdU in hard tissues including bone, tooth, and
      periodontal ligament. Mice were subcutaneously injected with BrdU (50 microg/g
      body weight) twice a day from the postnatal day 11 to day 15 and sacrificed at 2
      h after the last injection. Dissected maxillae were fixed (Bouin's solution or 4%
      paraformaldehyde), demineralized (Morse's solution or EDTA), and embedded in
      paraffin. Antigen retrieval procedures were performed before incubation with
      primary antibody. When sections were treated with HCl for DNA denaturation, the
      staining intensity of BrdU positive cells was not affected by difference of
      fixatives. Higher sensitivity was obtained by demineralization with Morse than
      with EDTA. Although heat-induced antigen retrieval techniques in citrate buffer
      (pH 6.0) showed as well or better sensitivity than acid pretreatment, heating
      caused tissue damage specifically to tooth dentine and the surrounding tissue.
      When the LRCs at four weeks after the last injection of BrdU were compared, much
      more LRCs were observed in specimen demineralized with Morse than with 10% EDTA.
      Our data suggest that demineralization with Morse with Bouin fixative plus HCl
      pretreatment gives rise to the optimal results for BrdU immunodetection in hard
      tissue.

PMID- 18718841
TI  - Heat shock protein 90 regulates development in Dictyostelium discoideum.
AB  - Cytosolic heat shock protein 90 (Hsp90) has been implicated in diverse biological
      processes such as protein folding, cell cycle control, signal transduction,
      development, and morphological evolution. Model systems available for studying
      Hsp90 function either allow ease of manipulation for biochemical studies or
      facilitate a phenomenological study of its role in influencing phenotype. In this
      work, we have explored the use of the cellular slime mold Dictyostelium
      discoideum to examine cellular functions of Hsp90 in relation to its
      multicellular development. In addition to cloning, purification, biochemical
      characterization, and examination of its crystal structure, our studies, using a
      pharmacological inhibitor of Hsp90, demonstrate a role for the cytoplasmic
      isoform (HspD) in D. discoideum development. Inhibition of HspD function using
      geldanamycin (GA) resulted in delayed aggregation and arrest of D. discoideum
      development at the 'mound' stage. Crystal structure of the amino-terminal domain
      of HspD showed a binding pocket similar to that described for yeast Hsp90.
      Fluorescence spectroscopy, as well as GA-coupled beads affinity pulldown,
      confirmed a specific interaction between HspD and GA. The results presented here
      provide an important insight into the function of HspD in D. discoideum
      development and emphasize the potential of the cellular slime mold to serve as an
      effective model for studying the many roles of Hsp90 at cellular and organismal
      levels.

PMID- 18718842
TI  - Specific interdomain synergy in the UapA transporter determines its unique
      specificity for uric acid among NAT carriers.
AB  - UapA, a uric acid-xanthine permease of Aspergillus nidulans, has been used as a
      prototype to study structure-function relationships in the ubiquitous nucleobase
      ascorbate transporter (NAT) family. Using novel genetic screens, rational
      mutational design, chimeric NAT molecules, and extensive transport kinetic
      analyses, we show that dynamic synergy between three distinct domains,
      transmembrane segment (TMS)1, the TMS8-9 loop, and TMS12, defines the function
      and specificity of UapA. The TMS8-9 loop includes four residues absolutely
      essential for substrate binding and transport (Glu356, Asp388, Gln408, and
      Asn409), whereas TMS1 and TMS12 seem to control, through steric hindrance or
      electrostatic repulsion, the differential access of purines to the TMS8-9 domain.
      Thus, UapA specificity is determined directly by the specific interactions of a
      given substrate with the TMS8-9 loop and indirectly by interactions of this loop
      with TMS1 and TMS12. We finally show that intramolecular synergy among UapA
      domains is highly specific and propose that it forms the basis for the evolution
      of the unique specificity of UapA for uric acid, a property not present in other
      NAT members.

PMID- 18718843
TI  - DMNQ-S17 inhibits constitutive NF-kappaB activation leading to induction of
      apoptosis through the activation of caspase-3 in human myeloid leukemia U937
      cells.
AB  - Through cytotoxicity screening with naphthoquinone derivatives, a novel compound
      6-(1-oxoallkyl)-5,8-dimethoxy-1,4-naphthoquinone-S17 (DMNQ-S17) showed its
      potency against human myeloid leukemia U937 cells. Thus, to elucidate the
      apoptotic mechanism of DMNQ-S17, this study was performed in myeloid leukemia
      U937 cells by 2,3-bis [2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5
      carboxanilide (XTT) assay, eletrophoretic mobility shift assay (EMSA), terminal
      deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay, 4',6
      diamidino-2-phenylindole (DAPI) staining, and Western blotting. In the present
      study, DMNQ-S17 inhibited constitutive NF kappaB activation and its
      transcriptional activity in U937 cells. In addition, DMNQ-S17 induced apoptotic
      features such as apoptotic bodies, cell shrinkage and chromatin condensation in
      U937 cells. Consistently, flow cytometric analysis showed that DMNQ-S17 increased
      sub-G1 portion and TUNEL positive cells in a concentration-dependent manner.
      Furthermore, DMNQ-S17 effectively attenuated mitochondrial membrane potential,
      released cytochrome C, activated caspase-3 expression, and cleaved poly (ADP
      ribose) polymerase (PARP). Reversely, caspase-3 and -9 inhibitors also blocked
      the DMNQ-S17 induced caspase-3 activation and PARP cleavage in U937 cells. Taken
      together, these findings suggest that DMNQ-S17 can be a potent anticancer
      candidate for myeloid leukemias by the suppression of NF-kappaB activation
      leading to the activation of caspase-3 in human myeloid leukemia U937 cells.

PMID- 18718844
TI  - Sucrose-induced obesity impairs novel object recognition learning in young rats.
AB  - In addition to its metabolic consequences, obesity may lead to impairments in
      learning and memory. To test this possibility, male Long-Evans rats were fed
      ground chow, or chow and either a 32% sucrose solution or hydrogenated vegetable
      fat (Crisco) for eight weeks. Cognitive behavior was then assessed using a novel
      object recognition task. To determine if there was a relationship between
      cognitive behavior and glucose metabolism, performance on the novel object
      recognition task was correlated with fasting blood glucose levels and responses
      on an oral glucose tolerance test. Rats fed sucrose or fat consumed more
      calories, gained more weight, and had larger epididymal fat pads than rats fed
      only chow. Additionally, fasting blood glucose levels, and the area under the
      glucose curve following an oral glucose tolerance test were greater in rats
      consuming a supplemental source of fat or sucrose than in those eating only chow.
      During training when rats were presented with two identical objects in an open
      field, time spent exploring the objects did not differ as a function of dietary
      conditions. However, when rats were tested 1 h later with one familiar and one
      novel object, rats given sucrose spent significantly less time exploring the
      novel object than rats eating only chow. The percent of time spent exploring the
      novel object was negatively correlated with fasting blood glucose levels, final
      body weights, and epididymal fat pad weights. It is hypothesized that the
      impairment in object recognition in rats eating sucrose is due, at least in part,
      to diet-induced alterations in glucose metabolism.

PMID- 18718845
TI  - Tityus serrulatus venom peptidomics: assessing venom peptide diversity.
AB  - MALDI-TOF-TOF and de novo sequencing were employed to assess the Tityus
      serrulatus venom peptide diversity. Previous works has shown the cornucopia of
      molecular masses, ranging from 800 to 3000Da, present in the venom from this and
      other scorpions species. This work reports the identification/sequencing of
      several of these peptides. The majority of the peptides found were fragments of
      larger venom toxins. For instance, 28 peptides could be identified as fragments
      from Pape proteins, 10 peptides corresponded to N-terminal fragments of the TsK
      beta (scorpine-like) toxin and fragments of potassium channel toxins (other than
      the k-beta) were sequenced as well. N-terminal fragments from the T. serrulatus
      hypotensins-I and II and a novel hypotensin-like peptide could also be found.
      This work also reports the sequencing of novel peptides without sequence
      similarities to other known molecules.

PMID- 18718846
TI  - Food, fun, and fitness internet program for girls: pilot evaluation of an e
      Health youth obesity prevention program examining predictors of obesity.
AB  - OBJECTIVE: This pilot study tested whether an Internet-based intervention could
      achieve change in fruit, juice, and vegetable consumption, physical activity, and
      self-efficacy in youth at-risk of obesity. METHOD: Participants were 80 8-to-10
      year-old African American girls at-risk of obesity, with a home computer,
      Internet access, and an e-mail address. A two-group design was followed. Groups
      differed only on incentive schedule (immediate, delayed). The 8-week home-based
      program, conducted entirely over the Internet, promoted fruit, juice, vegetables,
      and water intake and physical activity. Pre-post measures were collected through
      self-report via the program website. The study was conducted in the greater
      Houston, TX, area September through November, 2004. RESULTS: Statistically
      significant pre-to-post differences were observed in fruit, juice, and vegetable
      consumption (p=.002), physical activity--yesterday (p<.001), physical activity-
      usually (p=.001), and fruit, juice, and vegetable self-efficacy (p=.003).
      CONCLUSION: Internet-based obesity prevention programs may be an effective
      channel for promoting healthy diet and physical activity behaviors to youth at
      risk of obesity. Additional research is needed to more fully examine their
      effectiveness at promoting and maintaining diet and physical activity change.

PMID- 18718847
TI  - Features of public open spaces and physical activity among children: findings
      from the CLAN study.
AB  - OBJECTIVE: To examine associations between features of public open spaces, and
      children's physical activity. PARTICIPANTS: 163 children aged 8-9 years and 334
      adolescents aged 13-15 years from Melbourne, Australia participated in 2004.
      METHODS: A Geographic Information System was used to identify all public open
      spaces (POS) within 800 m of participants' homes and their closest POS. The
      features of all POS identified were audited in 2004/5. Accelerometers measured
      moderate-to-vigorous physical activity (MVPA) after school and on weekends.
      Linear regression analyses examined associations between features of the closest
      POS and participants' MVPA. RESULTS: Most participants had a POS within 800 m of
      their home. The presence of playgrounds was positively associated with younger
      boys' weekend MVPA (B=24.9 min/day; p< or =0.05), and lighting along paths was
      inversely associated with weekend MVPA (B=-54.9 min/day; p< or =0.05). The number
      of recreational facilities was inversely associated with younger girls' MVPA
      after school (B=-2.6 min/day; p< or =0.05) and on the weekend (B=-8.7 min/day; p<
      or =0.05). The presence of trees providing shade (5.8 min/day, p< or =0.01) and
      signage regarding dogs (B=6.8 min/day, p< or =0.05) were positively associated
      with adolescent girls' MVPA after school. CONCLUSION: Certain features of POS
      were associated with participants' MVPA, although mixed associations were
      evident. Further research is required to clarify these complex relationships.

PMID- 18718848
TI  - Therapeutics for neonatal brain injury.
AB  - Neonatal brain injury is an important cause of death and neurodevelopmental
      delay. Multiple pathways of oxidant stress, inflammation, and excitotoxicity lead
      to both early and late phases of cell damage and death. Therapies targeting these
      different pathways have shown potential in protecting the brain from ongoing
      injury. More recent therapies, such as growth factors, have demonstrated an
      ability to increase cell proliferation and repair over longer periods of time.
      Even though hypothermia, which decreases cerebral metabolism and possibly affects
      other mechanisms, may show some benefit in particular cases, no widely effective
      therapeutic interventions for human neonates exist. In this review, we summarize
      recent findings in neuroprotection and neurogenesis for the immature brain,
      including combination therapy to optimize repair.

PMID- 18718849
TI  - A latex agglutination assay for specific detection of Panton-Valentine
      leukocidin.
AB  - Panton-Valentine leukocidin (PVL) is produced by some isolates of Staphylococcus
      aureus, and has been associated with the high pathogenic potential of these
      strains. To rapidly detect the toxin producer strains, we developed a reverse
      passive latex agglutination (RPLA) reaction assay specific for PVL. By testing 64
      S. aureus strains, the assay could detect the 35 pvl-gene-positive strains with
      100% specificity and sensitivity. Furthermore, the assay revealed an extensive
      variation in the amount of PVL produced by the pvl-positive strains.

PMID- 18718850
TI  - Analysis of major band of Enterobacter sakazakii by ERIC-PCR and development of a
      species-specific PCR for detection of Ent. sakazakii in dry food samples.
AB  - ERIC (Enterobacterial Repetitive Intergenic Consensus)-PCR was employed to
      generate stable and reproductive ERIC-PCR fingerprints of Ent. sakazakii
      ATCC51329. Moreover, this study also cloned and sequenced a major band of Ent.
      sakazakii (ATCC51329) ERIC-PCR fingerprints. The major band was amplified with
      primer ERIC2 and sequences extending primer ERIC 2 showed poor similarity with
      ERIC elements. A comparison of the nucleotide acid with other sequences available
      in the GenBank revealed 90% of identity with Ent. sakazakii ATCC BAA-894, and 73%
      74% of identity with oligopeptiase gene or protease gene of some species from the
      Enterobacteriaceae family. Two primers were synthesized to develop and optimize
      an Enterobacter sakazakii-specific PCR based on regions of major band unique to
      Ent. sakazakii. The expected fragment was amplified from all of Ent. sakazkaii
      but not from the negative controls. As few as 10(2) CFU/ml of Ent. sakazakii of
      PCR were directly detected in the infant formulas. This was the case even in the
      presence of other bacteria. A comparison of traditional methods and new developed
      PCR in commercial foods suggested that without using API20-E test, the DFI
      chromogenic medium and FDA method showed 46.15% and 50% false positive
      respectively. Moreover, one false negative was observed with FDA method. In
      contrast, PCR was highly sensitive and specific to Ent. sakazakii. A high
      heterogeneity between Ent. sakazakii and the other microorganisms was found on
      expected fragment sequence. In addition, Ent. sakazakii ATCC51329 formed a
      separate branch with >5% divergence from the type strain ATCC BAA-894 and major
      strains.

PMID- 18718851
TI  - Construction of a non toxic chimeric protein (L1-L2-B) of Haemolysin BL from
      Bacillus cereus and its application in HBL toxin detection.
AB  - Among the many potential virulence factors of B. cereus, Haemolysin BL is a
      unique and potent three component pore forming toxin composed of a binding
      component, B, and two lytic components, L(1) and L(2). Heterogeneity in nucleic
      acid and protein sequences of HBL components and problems during expression of
      L(1) and L(2) proteins in recombinant host due to their toxicity causes problems
      for development of specific detection systems based on PCR and Immunoassay,
      respectively. Commercially available kit (BCET RPLA, Oxoid) is useful for
      detection of L(2) component of HBL, but detection of only one component is
      insufficient to give comprehensive view on HBL toxin producing strains as some
      strains produced only one or two of the three HBL components. To address above
      mentioned problems, in this study, we cloned conserved domains of B, L(1) and
      L(2) components together as single fusion gene and expressed as recombinant
      multidomain chimeric protein in E. coli. The resultant protein having L(1), B and
      L(2) components in the form of single protein had no toxicity towards E. coli as
      we followed truncated protein approach. The hyperimmune antisera raised in mice
      against r-chimeric protein reacted with all the three components of HBL toxin of
      B. cereus (ATCC 14579) and provided three reaction bands at ~40 kDa to ~50 kDa
      regions during Western blot analysis. The hyperimmune sera of r-chimeric protein
      also notably neutralized the hemolytic activity of native HBL toxin. These
      results demonstrated that the obtained chimeric protein is correct and retained
      the antigenicity of native HBL toxin components. Therefore, it has better
      application in the development of a comprehensive HBL detection immunoassay and
      may also be a potential candidate molecule for vaccine studies.

PMID- 18718852
TI  - A standardized pre-treatment method of biofilm flocs for fluorescence microscopic
      characterization.
AB  - The availability of epifluorescence microscopy opens the door for the
      visualization of biofilm flocs via the fluorescence staining technique. However,
      one of the main problems in the application of the method is a missing
      standardized protocol for sample preparation. In this study, different pre
      treatment methods for the simultaneous staining of different sludge flocs
      components e.g. extracellular polymeric substances (EPS) and microorganisms (MO)
      were compared. A method was chosen, which remains the shape of sludge flocs from
      a municipal wastewater treatment plant and allows to stain major parts of the
      flocs thoroughly: For this the surrounding wastewater was removed by
      centrifugation. Then the flocs were resuspended in sterile tap water, immobilized
      by drying on a diagnostic slide and fixated with formaldehyde. The staining of
      the different compounds was performed with tetramethylrhodamine isothiocyanate
      labeled lectin Concanavalin A (TRITC-Con A; glycoconjugates),
      fluoresceinisothiocyanate isomer I (FITC; amino groups) and 4,6-diamidino-2
      phenylindoldihydrochloride (DAPI; nucleic acids). This staining method was
      successfully applied for protein- and carbohydrate-quantification using gelatin
      mixtures of dextran and bovine serum albumin (BSA). The pre-treatment and
      staining methods were appropriate to compare the composition of different biofilm
      flocs such as nitrifying activated sludge from a municipal wastewater treatment
      plant and a pure culture of the bacterial strain Pseudomonas putida (ATCC 17514)
      as revealed by the results of conventional analytical methods.

PMID- 18718853
TI  - Developmental changes in startle reactivity in school-age children at risk for
      and with actual anxiety disorder.
AB  - The present study examined the development of elevated startle reactivity in
      anticipation of mild anxiogenic procedures in school-age children with current
      anxiety disorders and in those at-risk for their development due to parental
      anxiety. Startle blink reflexes and skin conductance responses were assessed in 7
      to 12 year old anxious children (N=21), non-anxious children at-risk for anxiety
      by virtue of parental anxiety disorder status (N=16) and non-anxious control
      children of non-anxious parents (N=13). Responses were elicited by 28 auditory
      startle stimuli presented prior to undertaking mild anxiogenic laboratory
      procedures. Results showed that group differences in startle reactivity differed
      as a function of children's age. Relative to control children for whom age had no
      effect, startle reflex magnitude in anticipation of anxiogenic procedures
      increased across the 7 to 12 years age range in children at-risk for anxiety
      disorders, whereas elevations in startle reactivity were already manifest from a
      younger age in children with anxiety disorders. These findings may suggest an
      underlying vulnerability that becomes manifest with development in offspring of
      anxious parents as the risk for anxiety disorders increases.

PMID- 18718854
TI  - Dynamic microPET imaging of ultrasound contrast agents and lipid delivery.
AB  - Interest in ultrasound contrast agents (lipid-shelled microbubbles) as delivery
      vehicles is increasing; however, the biodistribution of these agents remains
      uncharacterized, both with and without ultrasound. In this study, an (18)F
      labeled lipid ([(18)F]fluorodipalmitin), incorporated in microbubble shells, was
      used as a dynamic microPET probe for quantitative 90-minute biodistribution
      measurements in male Fischer 344 rats (n=2). The spleen retained the highest
      concentration of radioactive lipid at approximately 2.6%-injected dose per cubic
      centimeter (% ID/cc) and the liver demonstrated the largest total accumulation
      (approximately 17% ID). The microbubble pharmacokinetic profile differed from
      free lipid, which is rapidly cleared from blood, and liposomes, which remain in
      circulation. Additionally, region of interest (ROI) analysis over 60 minutes
      (post-ultrasound treatment) quantified the delivery of lipid by therapeutic
      ultrasound from microbubbles to kidney tissue (n=8). The ultrasound sequence
      consisted of a 200 kPa, 5.3 MHz radiation force pulse followed by a 1.6 MPa, 1.4
      MHz fragmentation pulse and was applied to one kidney, while the contralateral
      kidney served as a control. ROI-estimated activity in treated kidneys was
      slightly but significantly greater at 0 and 60 min than in untreated kidneys
      (p=0.0012 and 0.0035, respectively). This effect increased with the number of
      microbubbles injected (p=0.006). In summary, [(18)F]fluorodipalmitin was used to
      characterize the biodistribution of contrast microbubble shells and the
      deposition of lipid was shown to be locally increased after insonation.

PMID- 18718855
TI  - Rapid induction of OX40 ligand on primary T cells activated under DNA-damaging
      conditions.
AB  - We have previously demonstrated that normal human T cells either long-term
      repeatedly stimulated or freshly activated in vitro in the presence of TGF-beta
      express the cell surface T-cell costimulating molecule OX40 ligand (OX40L). To
      further elucidate the kinetics of OX40L expression by human T cells, we have
      examined whether cell proliferation was required for the expression of OX40L.
      Thus, normal fresh peripheral blood mononuclear cells were stimulated with
      immobilized anti-CD3 antibody in the presence of the DNA synthesis-blocking
      agents such as mitomycin C, 5-fluorouracil, or X-ray irradiation. Flow cytometric
      analyses demonstrated that a significant frequency of these DNA-damaged activated
      primary CD4+ and CD8+ T cells became OX40L+ as early as 1 hour after treatment.
      The OX40L induction on the DNA-damaged activated T cells was inhibited by
      treatment with either RNA or protein synthesis inhibitors, actinomycin D, or
      cycloheximide, respectively. Induced OX40L on T cells was functional because it
      bound recombinant OX40. These data indicate that human primary T cells are
      programmed to rapidly express functional OX40L molecules after stimulation under
      DNA-damaging conditions, demonstrating that the induction of OX40L by T cells is
      independent of cell proliferation. The clinical implications of these new
      findings are discussed.

PMID- 18718856
TI  - Allelic diversity of MICA gene and MICA/HLA-B haplotypic variation in a
      population of the Murcia region in southeastern Spain.
AB  - Major histocompatibility complex class I-related chain A (MICA) is located at 46
      kb centromeric of HLA-B. It is highly polymorphic and interacts with NKG2D, its
      receptor on the surface of NK, Tgammadelta and T CD8 lymphocytes. Data on MICA
      polymorphism in different populations are still limited. Our aim was to establish
      allelic diversity of MICA gene and linkage disequilibrium with HLA-B in our
      population. DNA was obtained from 154 unrelated healthy individuals from the
      Murcia region in southeastern Spain. HLA-B genotyping was performed using
      polymerase chain reaction (PCR)-sequence-specific oligonucleotide probes and
      allele-specific PCR-sequence-specific primers, and MICA genotyping by using PCR
      sequence-specific oligonucleotide probes. A total of 19 MICA alleles were
      detected on this study. MICA*008 was the most frequent allele (25.3%), followed
      by MICA*002 (16.1%), MICA*004 (14.9%), MICA*001 (7.8%), MICA*009 and MICA*016
      (7.1%), and MICA*010 (4.6%). Eleven alleles had frequencies of <1%. In the
      haplotype analysis, MICA*008-B*0702 was found to be the most common, followed by
      MICA*004-B*4403 and MICA*001-B*1801, MICA*002-B*3501, MICA*008-B*4402, MICA*004
      B*4901, MICA*008-B*0801, and MICA*002-B*3801. The frequency of MICA*010-B*1501,
      MICA*008-B*1302, MICA*015-B*4501, and MICA*008-B*4001 was remarkable inasmuch as
      these two last haplotypes have not been reported in Spanish population. Indeed,
      MICA*016 linked to B*1402 has also not been reported in the literature. In
      conclusion, the allelic diversity in our population is similar to other Caucasian
      populations; however we found a series of less frequent alleles, in addition to
      as-yet-undescribed haplotypic associations in other populations of Caucasian
      origin.

PMID- 18718857
TI  - Endothelial nitric oxide synthase gene polymorphism is associated with Behcet's
      disease in Tunisian population.
AB  - Nitric oxide (NO) is a molecule that plays a key role in many physiologic and
      pathologic processes. It is produced in vivo from the aminoacid l-arginine by a
      family of nitric oxide synthases (NOS). Endothelial NOS (eNOS) is a
      constitutively expressed isoform of NOS. The eNOS gene entails several
      polymorphisms, of which certain were investigated in Behcet's disease (BD). We
      sought to establish the association of eNOS gene Glu298Asp polymorphism in exon 7
      with susceptibility to BD. In this study, 135 Tunisian patients with BD and 157
      healthy blood donor controls from the same geographic area were genotyped by
      polymerase chain reaction technique for eNOS polymorphism in exon 7. Our results
      showed that the distribution of the Glu298Asp genotype differed between BD
      patients and controls but did not reach statistical significance (p = 0.06).
      Allele Asp298 was significantly more frequent in healthy controls than in BD
      patients (p = 0.037, chi(2) = 4.33, OR = 1.01, 95% CI = 1.41-1.99). A significant
      difference was found (p = 0.004, OR = 1.26, 95% CI = 2.13-3.62) between BD
      patients with skin lesions and patients without this manifestation. Our findings
      suggest that Glu298Asp polymorphism of eNOS gene is associated with BD
      susceptibility as well as skin lesions.

PMID- 18718858
TI  - Cold-adapted tubulins in the glacier ice worm, Mesenchytraeus solifugus.
AB  - Glacier ice worms, Mesenchytraeus solifugus and related species, are the only
      known annelids that survive obligately in glacier ice and snow. One fundamental
      component of cold temperature adaptation is the ability to polymerize tubulin,
      which typically depolymerizes at low physiological temperatures (e.g., <10
      degrees C) in most temperate species. In this study, we isolated two alpha
      tubulin (Msalpha1, Msalpha2) and two beta-tubulin (Msbeta1, Msbeta2) subunits
      from an ice worm cDNA library, and compared their predicted amino acid sequences
      with homologues from other cold-adapted organisms (e.g., Antarctic fish, ciliate)
      in an effort to identify species-specific amino acid substitutions that
      contribute to cold temperature-dependent tubulin polymerization. Our comparisons
      and predicted protein structures suggest that ice worm-specific amino acid
      substitutions stabilize lateral contact associations, particularly between beta
      tubulin protofilaments, but these substitutions occur at different positions in
      comparison with other cold-adapted tubulins. The ice worm tubulin gene family
      appears relatively small, comprising one primary alpha- and one primary beta
      tubulin monomers, though minor isoforms and pseudogenes were identified. Our
      analyses suggest that variation occurs in the strategies (i.e., species-specific
      amino acid substitutions, gene number) by which cold-adapted taxa have evolved
      the ability to polymerize tubulin at low physiological temperatures.

PMID- 18718860
TI  - Differential expression of specific FGF ligands and receptor isoforms during
      osteogenic differentiation of mouse Adipose-derived Stem Cells (mASCs)
      recapitulates the in vivo osteogenic pattern.
AB  - The ability of Adipose-derived Stem Cells (ASCs) to differentiate into various
      tissues in vitro and in vivo, a function known as "stem cell plasticity", makes
      them an appealing cell source for tissue engineering. Our laboratory is
      particularly focused on the potential role of adipose tissue as a readily
      available postnatal source of osteoprogenitor. Fibroblast growth factors (FGF)
      and their receptors (FGFR) are important regulators of osteogenesis. The goal of
      this study was to elucidate how changes in temporal expression patterns of
      individual components of the fibroblast growth factor (FGF) signaling axis
      correlate with osteogenic differentiation of mASCs. Our results indicate that FGF
      ligand genes, such as Fgf-2, -4, -8, and -18, displayed a differential and
      dynamic profile during mouse ASC (mASC) osteogenesis. Fgf-2 transcript was down
      regulated, while Fgf-18 transcript level was strongly up-regulated.
      Interestingly, a drift in the ratio of different FGF-2 protein forms, with
      translation favoring the HMWFGF-2 forms, occurred during osteogenic
      differentiation, whereas, the expression of LMWFGF-2 form was down-regulated.
      This finding shares similarity with a previous study suggesting that preferential
      expression of the HMWFGF-2 forms is associated with a more osteogenic
      differentiated state of calvarial osteoblast. Moreover, a differential expression
      of Fgf Receptor 1 and 2 resembling that previously found in in vivo osteogenic
      study was observed. Thus, mASCs undergoing osteogenesis recapitulate the in vivo
      osteogenic differentiation expression pattern of FGF ligands and receptors of
      calvarial mesenchymal cells during their own osteogenic differentiation. Indeed,
      this observation further validates ASCs as a suitable resource for skeletal
      tissue engineering.

PMID- 18718859
TI  - Alternative splicing in the NF-kappaB signaling pathway.
AB  - Activation of transcription factor NF-kappaB can affect the expression of several
      hundred genes, many of which are involved in inflammation and immunity. The
      proper NF-kappaB transcriptional response is primarily regulated by post
      translational modification of NF-kappaB signaling constituents. Herein, we review
      the accumulating evidence suggesting that alternative splicing of NF-kappaB
      signaling components is another means of controlling NF-kappaB signaling. Several
      alternative splicing events in both the tumor necrosis factor and
      Toll/interleukin-1 NF-kappaB signaling pathways can inhibit the NF-kappaB
      response, whereas others enhance NF-kappaB signaling. Alternative splicing of
      mRNAs encoding some NF-kappaB signaling components can be induced by prolonged
      exposure to an NF-kappaB-activating signal, such as lipopolysaccharide,
      suggesting a mechanism for negative feedback to dampen excessive NF-kappaB
      signaling. Moreover, some NF-kappaB alternative splicing events appear to be
      specific for certain diseases, and could serve as therapeutic targets or
      biomarkers.

PMID- 18718861
TI  - Molecular and phylogenetic characterization of cytochromes c from Haemonchus
      contortus and Trichostrongylus vitrinus (Nematoda: Trichostrongylida).
AB  - Although cytochrome c genes (cyt c) and proteins (CYT C) have been relatively
      well studied in mammals, very little is known about them in parasitic helminths.
      In the present study, we investigated this group of molecules in Haemonchus
      contortus (barber's pole worm) and Trichostrongylus vitrinus (black scour worm),
      two parasitic nematodes of small ruminants. The cyt c gene (512 bp) of H.
      contortus had one intron and encoded a transcript of 345 nucleotides, whilst that
      of T. vitrinus (792 bp) had two introns and encoded a transcript of 360
      nucleotides. The transcription of cyt c in T. vitrinus was substantially greater
      in adult males compared with females, although no such gender-enrichment was
      evident in adults of H. contortus. These findings were supported at the protein
      level by immunoblot analyses. The inferred proteins (designated Hc-CYT C and Tv
      CYT C, respectively) shared nucleotide and amino acid identities of 78% and 85%,
      respectively. The alignment of these and other CYT C sequences from nematodes,
      flatworms, insects and mammals identified conserved motifs associated with CYT C
      oxidase- and reductase- as well as haem-binding. One residue (histidine-26) was
      conserved for mammals, whereas this residue was absent from all nematodes; the
      functional significance of this difference is not yet known. Both phylogenetic
      analysis and protein modelling revealed that CYT C proteins of nematodes are
      structurally distinct from those of mammals and other organisms, suggesting their
      potential as targets for parasite intervention.

PMID- 18718862
TI  - Acute behavioural and neurotoxic effects of MDMA plus cocaine in adolescent mice.
AB  - The poly-drug pattern is the most common among those observed in MDMA users, with
      cocaine being a frequently associated drug. This study evaluates the acute
      effects of MDMA (5, 10 and 20 mg/kg), alone or in combination with cocaine (25
      mg/kg), on motor activity, anxiety (elevated plus maze and social interaction
      test), memory and brain monoamines in adolescent mice. Both drugs, administered
      alone or concurrently, produced hyperactivity and a decrease in social contacts.
      However, an anxiolytic effect, studied by means of the elevated plus maze and
      expressed as an increase in the time spent on the open arms, was observed only in
      those animals treated with cocaine and MDMA. The passive avoidance task was
      affected only with the highest MDMA dose (20 mg/kg). Mice treated with MDMA did
      not present significant changes in brain monoamines, while those receiving MDMA
      and cocaine showed a decrease in DA in the striatum, which was accompanied by an
      increase in the serotonin concentration in the striatum and cortex 30 min after
      acute administration. In conclusion, the combined use of MDMA and cocaine
      produces a predominance of serotonin over DA, which is associated with an
      anxiolytic profile, defensive behaviours and fewer social contacts.

PMID- 18718863
TI  - CREB-dependent gene regulation by prion protein: impact on MMP-9 and beta
      dystroglycan.
AB  - Corruption of the normal function of the cellular prion protein (PrP(C)) by the
      scrapie isoform (PrP(Sc)) emerges as a critical causal event in Transmissible
      Spongiform Encaphalopathies (TSE) pathogenesis. However, PrP(C) physiological
      role remains unclear. By exploiting the properties of the 1C11 neuroectodermal
      cell line, able to convert into 1C11(5-HT) serotonergic or 1C11(NE) noradrenergic
      neuronal cells, we assigned a signaling function to PrP(C). Here, we establish
      that antibody-mediated PrP(C) ligation promotes the recruitment of the cAMP
      responsive element binding protein (CREB) transcription factor downstream from
      the MAPK ERK1/2, in 1C11 precursor cells and their 1C11(5-HT) and 1C11(NE)
      neuronal progenies. Whatever the differentiation state of 1C11 cells, the PrP(C)
      dependent CREB activation triggers Egr-1 and c-fos transcription, two immediate
      early genes that relay CREB's role in cell survival and proliferation as well as
      in neuronal plasticity. Furthermore, in 1C11-derived neuronal cells, we draw a
      link between the PrP(C)-CREB coupling and a transcriptional regulation of the
      metalloproteinase MMP-9 and its inhibitor TIMP-1, which play pivotal roles in
      neuronal pathophysiology. Finally, the PrP(C)-dependent control on MMP-9 impacts
      on the processing of the transmembrane protein, beta-dystroglycan. Taken
      together, our data define molecular mechanisms that likely mirror PrP(C)
      ubiquitous contribution to cytoprotection and its involvement in neuronal
      plasticity.

PMID- 18718864
TI  - The invertebrate B(0) system transporter, D. melanogaster NAT1, has unique d
      amino acid affinity and mediates gut and brain functions.
AB  - The CG3252 gene product, DmNAT1, represents the first Nutrient Amino acid
      Transporter cloned from Drosophila. It absorbs a broader set of neutral amino
      acids versus earlier characterized insect NATs and mammalian NATs-B(0) system
      transporters from the Sodium Neurotransmitter symporter Family (SNF, a.k.a.
      solute carrier family 6, SLC6). In addition to B(0)-specific l-substrates, DmNAT1
      equally or more effectively transports d-amino acids with sub-millimolar
      affinities and 1:1 sodium:amino acid transport stoichiometry. DmNAT1 is strongly
      transcribed in the absorptive and secretory regions of the larval alimentary
      canal and larval brain, revealing its roles in the primary absorption and
      redistribution of large neutral l-amino acids as well as corresponding d-isomers.
      The absorption of d-amino acids via DmNAT1 may benefit the acquisition of
      fermented and symbiotic products, and may support the unique capacity of fruit
      fly larvae to utilize a diet with substitution of essential amino acids by d
      isomers. It also suggests a remarkable adaptive plasticity of NAT-SLC6 mechanisms
      via alterations of a few identifiable sites in the substrate-binding pocket. The
      strong transcription in the brain suggests roles for DmNAT1 in neuronal nutrition
      and clearance of l-neutral amino acids from the fly brain. In addition, neuronal
      DmNAT1 may absorb synaptic d-serine and modulate NMDA receptor-coupled signal
      transduction. The characterization of the first invertebrate B(0)-like
      transporter extends the biological roles of the SLC6 family, revealing
      adaptations for the absorption of d-isomers of the essential amino acids. These
      findings suggest that some members of the NAT-SLC6 subfamily are evolving
      specific properties which contribute to nutrient symbiotic relationships and
      neuronal functions.

PMID- 18718865
TI  - Porcine CFSE mixed lymphocyte reaction and PKH-26 cell-mediated lympholysis
      assays.
AB  - Mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) are widely
      used to assess T cell responses. A major limitation of the traditional MLR and
      CML assays is that they require radioisotope labeling with (3)H for MLR and
      (51)Cr for CML, thereby limiting their use to laboratories with the capabilities
      to deal safely with these materials. Recently, flow cytometry with CFSE labeling
      has been used to detect cell division in rodent and human assays, and flow
      cytometry with PKH-26 labeling has been used to study cytotoxicity in murine
      models. Partially inbred miniature swine provide a unique large animal
      preclinical model for experimental transplantation, helping to bridge the gap
      between rodent and clinical studies. In this study, we modified the reported CFSE
      and PKH-26 labeling procedures for use with porcine cells, and established that
      these radioactive-free MLR and CML assays are comparable to traditional
      radioactive CML and MLR assays for assessing immunologic responses in miniature
      swine. To our knowledge, this is the first report that has directly compared the
      traditional CML/MLR with radiation-free CML/MLR in MHC-defined swine models.
      OBJECTIVE: The aim of this study is to establish non-radiolabeled CSFE and PKH-26
      labeling procedures for flow cytometry based CML/MLR assays that are comparable
      to radioactive CML/MLR assays in preclinical large animals.

PMID- 18718866
TI  - MANF is widely expressed in mammalian tissues and differently regulated after
      ischemic and epileptic insults in rodent brain.
AB  - The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been described
      as a survival factor for dopaminergic neurons in vitro, but its expression in
      mammalian tissues is poorly known. MANF and a homologous protein, the conserved
      dopamine neurotrophic factor (CDNF), form a novel evolutionary conserved family
      of neurotrophic factors. Here we used in situ hybridization and
      immunohistochemistry to characterize MANF expression in developing and adult
      mouse. MANF expression was widespread in the nervous system and non-neuronal
      tissues. In the brain, relatively high MANF levels were detected in the cerebral
      cortex, hippocampus and cerebellar Purkinje cells. After status epilepticus, Manf
      mRNA expression was transiently increased in the dentate granule cell layer of
      hippocampus, thalamic reticular nucleus and in several cortical areas. In
      contrast, following global forebrain ischemia changes in Manf expression were
      widespread in the hippocampal formation and more restricted in cerebral cortex.
      The widespread expression of MANF together with its evolutionary conserved nature
      and regulation by brain insults suggest that it has important functions both
      under normal and pathological conditions in many tissue types.

PMID- 18718867
TI  - Depletion of central BDNF in mice impedes terminal differentiation of new granule
      neurons in the adult hippocampus.
AB  - Granule neurons generated in the adult mammalian hippocampus synaptically
      integrate to facilitate cognitive function and antidepressant efficacy. Here, we
      investigated the role of BDNF in facilitating their maturation in vivo. We found
      that depletion of central BDNF in mice elicited an increase in hippocampal cell
      proliferation without affecting cell survival or fate specification. However, new
      mutant neurons failed to fully mature as indicated by their lack of calbindin,
      reduced dendritic differentiation and an accumulation of calretinin(+) immature
      neurons in the BDNF mutant dentate gyrus. Furthermore, the facilitating effects
      of GABA(A) receptor stimulation on neurogenesis were absent in the mutants,
      suggesting that defects might be due to alterations in GABA signaling.
      Transcriptional analysis of the mutant hippocampal neurogenic region revealed
      increases in markers for immature neurons and decreases in neuronal
      differentiation facilitators. These findings demonstrate that BDNF is required
      for the terminal differentiation of new neurons in the adult hippocampus.

PMID- 18718868
TI  - Progenitors from the postnatal forebrain subventricular zone differentiate into
      cerebellar-like interneurons and cerebellar-specific astrocytes upon
      transplantation.
AB  - Forebrain subventricular zone (SVZ) progenitor cells give rise to glia and
      olfactory bulb interneurons during early postnatal life in rats. We investigated
      the potential of SVZ cells to alter their fate by transplanting them into a
      heterotypic neurogenic and gliogenic environment-the cerebellum. Transplanted
      cells were examined 1 to 7 weeks and 6 months post transplantation. Forebrain
      progenitors populated the cerebellum and differentiated into oligodendrocytes,
      cerebellar-specific Bergmann glia and velate astrocytes, and neurons. The
      transplanted cells that differentiated into neurons maintained an interneuronal
      fate: they were GABA-positive, expressed interneuronal markers, such as
      calretinin, and exhibited membrane properties that are characteristic of
      interneurons. However, the transplanted interneurons lost the expression of the
      olfactory bulb transcription factors Tbr2 and Dlx1, and acquired a cerebellar
      like morphology. Forebrain SVZ progenitors thus have the potential to adapt to a
      new environment and integrate into diverse regions, and may be a useful tool in
      transplantation strategies.

PMID- 18718869
TI  - Effects of rutin from Toona sinensis on the immune and physiological responses of
      white shrimp (Litopenaeus vannamei) under Vibrio alginolyticus challenge.
AB  - Rutin is a bioflavonoid with strong antioxidant activity. To investigate the
      regulatory roles of rutin in various functions in crustaceans, we examined
      physiological (haemolymph glucose, lactate, and lipid) and innate non-specific
      immune responses (total haemocyte count (THC), phenoloxidase activity (PO),
      respiratory bursts (release of superoxide anion, O(2)(-)) and superoxide
      dismutase (SOD) activity) to the pathogen Vibrio alginolyticus in white shrimp
      (Litopenaeus vannamei) that were individually injected with rutin extracted from
      Toona sinensis at 10, 20, or 50 microg g(-1). Results showed that PO activity and
      respiratory burst of L. vannamei increased obviously (P<0.05) when injected with
      rutin at a dose of 20 and 50 microg g(-1) after 12 and 24 h, respectively. Both
      the THC and SOD activities of experimental and control groups revealed no
      significant difference at all doses. L. vannamei injected with rutin at either
      dose maintained lower glucose, lactate, and lipid levels in response to V.
      alginolyticus challenge after 12-36, 24-48, and 24-60 h, respectively. The
      survival rate of L. vannamei that received rutin at either dose was significantly
      higher than that received saline after 48-72 h. It was, therefore, concluded that
      the immune ability and resistance against V. alginolyticus infection of L.
      vannamei receiving rutin at > or = 10 microg g(-1) increased.

PMID- 18718870
TI  - Dynamical causal modelling for M/EEG: spatial and temporal symmetry constraints.
AB  - We describe the use of spatial and temporal constraints in dynamic causal
      modelling (DCM) of magneto- and electroencephalography (M/EEG) data. DCM for
      M/EEG is based on a spatiotemporal, generative model of electromagnetic brain
      activity. The temporal dynamics are described by neural-mass models of equivalent
      current dipole (ECD) sources and their spatial expression is modelled by
      parameterized lead-field functions. Often, in classical ECD models, symmetry
      constraints are used to model homologous pairs of dipoles in both hemispheres.
      These constraints are motivated by assumptions about symmetric activation of
      bilateral sensory sources. In classical approaches, these constraints are 'hard';
      i.e. the parameters of homologous dipoles are shared. Here, in the context of
      DCM, we illustrate the use of informed Bayesian priors to implement 'soft'
      symmetry constraints that are expressed in the posterior estimates only when
      supported by the data. Critically, with DCM one can deploy symmetry constraints
      in either the temporal or spatial components of the model. This enables one to
      test for symmetry in temporal (neural-mass) parameters in the presence of non
      symmetric spatial expressions of homologous sources (and vice versa).
      Furthermore, we demonstrate that Bayesian model comparison can be used to
      identify the best models among a range of symmetric and non-symmetric variants.
      Our main finding is that the use of 'soft' symmetry priors is recommended for
      evoked responses to bilateral sensory input. We illustrate the use of symmetry
      constraints in DCM on synthetic and real EEG data.

PMID- 18718871
TI  - Serotonin transporter genotype and depressive phenotype determination by
      discriminant analysis of glucose metabolism under acute tryptophan depletion.
AB  - Acute tryptophan depletion (ATD) putatively results in a transient reduction in
      central serotonin transmission, and induces depressed mood in some un-medicated
      subjects with remitted major depressive disorder (MDD). The 5-HT transporter
      promoter region length polymorphism (5-HTTLPR) has been shown to influence
      behavioral and metabolic responses to ATD, as well as the risk for developing MDD
      within the context of stress. The current study investigates the relationships
      between 5-HTTLPR genotype, neurophysiologic response to ATD, and diagnostic
      phenotype (healthy control subjects versus MDD subjects differentiated by their
      depressive response to ATD) using (18)FDG-PET. Un-medicated subjects with
      remitted MDD and healthy controls were genotyped for the long (l) and short (s)
      alleles of the 5-HTTLPR polymorphism and categorized into one of three genotypes.
      On two separate occasions, subjects received either a placebo or an amino acid
      mixture designed to deplete plasma tryptophan, followed by (18)FDG-PET scanning.
      Depressive symptoms were rated to determine the diagnostic phenotype. Descriptive
      and predictive discriminant analyses were performed using brain regional
      metabolic data to classify according to phenotype and genotype. Overall, 79% of
      the cases were classified correctly by genotype, and 85% were classified
      correctly by phenotype. In a leave-one-out cross-validation, 72% of the subjects
      were classified correctly as carrying an s-allele, and 79% of the subjects were
      classified correctly by primary diagnosis. The robust nature of the
      classification results indicates that much of the variance in metabolic response
      to ATD is accounted for by genotypic and phenotypic category.

PMID- 18718873
TI  - Mechanism of modulation of the plasma membrane Ca(2+)-ATPase by arachidonic acid.
AB  - The intracellular level of long chain fatty acids controls the Ca(2+)
      concentration in the cytoplasm. The molecular mechanisms underlying this Ca(2+)
      mobilization are not fully understood. We show here that the addition of low
      micromolar concentrations of fatty acids directly to the purified plasma membrane
      Ca(2+)-ATPase enhance ATP hydrolysis, while higher concentration decrease
      activity, exerting a dual effect on the enzyme. The effect of arachidonic acid is
      similar in the presence or absence of calmodulin, acidic phospholipids or ATP at
      the regulatory site, thereby precluding these sites as probable acid binding
      sites. At low arachidonic acid concentrations, neither the affinity for calcium
      nor the phosphoenzyme levels are significantly modified, while at higher
      concentrations both are decreased. The action of arachidonic acid is isoenzyme
      specific. The increase on ATP hydrolysis, however, is uncoupled from calcium
      transport, because arachidonic acid increases the permeability of erythrocyte
      membranes to calcium. Oleic acid has no effect on membrane permeability while
      linoleic acid shows an effect similar to that of arachidonic acid. Such effects
      might contribute to the entry of extracellular Ca(2+) following to fatty acid
      release.

PMID- 18718874
TI  - New findings on sperm ultrastructure in thrips (Thysanoptera, Insecta).
AB  - Sperm ultrastructure of several species in each of the two suborders of
      Thysanoptera Tubulifera and Terebrantia shows a distinctive and unusual
      architecture. Members of the whole order share a bizarre axoneme consisting of 27
      microtubular elements derived from the amalgamation of 3 (9+0) axonemes present
      in each spermatid at the beginning of spermiogenesis. The reciprocal shifting of
      these axonemes along the length of the sperm, together with their possible
      shortening and overlapping for short distances, could explain why in some species
      it is never possible to observe the complete set of 27 microtubular elements in
      any one cross section. Tubuliferan sperm have a small elliptical (in cross
      section) acrosome extending the length of the sperm. In Bolothrips insularis and
      Compsothrips albosignatus this structure is larger and is associated with an
      external, flattened vesicle throughout its length. Terebrantian sperm lack an
      acrosome, but display for half their length a dense body running parallel to the
      nucleus. The sperm, in members of this suborder, are also characterized by
      possession of a small mitochondrion and by the unusual bilobed outline of cross
      sections through the anterior sperm region, with the nucleus located in one of
      the two lobes. Structures serving to anchor sperm to the inner surface of the
      cyst cell have been observed at their anterior tips in the testes of
      tubuliferans. In B. insularis, an anterior appendage is formed in immature sperm
      and is maintained in the mature spermatozoon parallel to its long axis in the
      most anterior region. Such an anchoring structure has not been observed in sperm
      of the terebrantian species examined, probably because the testis of
      terebrantians contains only a single cyst of developing gametes.

PMID- 18718872
TI  - Network activation during bimanual movements in humans.
AB  - The coordination of movement between the upper limbs is a function highly
      distributed across the animal kingdom. How the central nervous system generates
      such bilateral, synchronous movements, and how this differs from the generation
      of unilateral movements, remain uncertain. Electrophysiologic and functional
      imaging studies support that the activity of many brain regions during bimanual
      and unimanual movement is quite similar. Thus, the same brain regions (and indeed
      the same neurons) respond similarly during unimanual and bimanual movements as
      measured by electrophysiological responses. How then are different motor
      behaviors generated? To address this question, we studied unimanual and bimanual
      movements using fMRI and constructed networks of activation using Structural
      Equation Modeling (SEM). Our results suggest that (1) the dominant hemisphere
      appears to initiate activity responsible for bimanual movement; (2) activation
      during bimanual movement does not reflect the sum of right and left unimanual
      activation; (3) production of unimanual movement involves a network that is
      distinct from, and not a mirror of, the network for contralateral unimanual
      movement; and (4) using SEM, it is possible to obtain robust group networks
      representative of a population and to identify individual networks which can be
      used to detect subtle differences both between subjects as well as within a
      single subject over time. In summary, these results highlight a differential role
      for the dominant and non-dominant hemispheres during bimanual movements, further
      elaborating the concept of handedness and dominance. This knowledge increases our
      understanding of cortical motor physiology in health and after neurological
      damage.

PMID- 18718875
TI  - Effect of beta-escin sodium on endothelial cells proliferation, migration and
      apoptosis.
AB  - beta-Escin, the major active compound in extracts of the horse chestnut Aesculus
      hippocastanum seed, has shown clinically significant activity in chronic venous
      insufficiency (CVI). Our previous studies had shown that beta-escin sodium
      inhibited angiogenesis in chick chorioallantoic membrane (CAM) and in aortic disk
      assay. In this study, we explored the direct effect of beta-escin sodium on
      proliferation, migration and apoptosis in human umbilical vein endothelial cells
      (HUVECs) and ECV304 cells. Sulforhodamine B (SRB) assay showed that beta-escin
      sodium (10, 20, 40 microg/ml) inhibited endothelial cells (ECs) proliferation
      dose-dependently. beta-escin sodium also induced ECs apoptosis at 40 microg/ml.
      Cell migration was evaluated by an improved wound assay: barren spot assay. And
      the direct effect on cell motility excluding influence of cell proliferation was
      examined by High Content Screening (HCS, Cellomics) assay. The data indicated
      that beta-escin sodium suppressed ECs migration and cell motility. Western blot
      results suggested that beta-escin sodium acts on ECs possibly by increasing
      expression of thrombospondin-1 (TSP-1), and decreasing expression of PKC-alpha
      and activation of p44/42 mitogen-activated protein kinase (ERK) and p38 mitogen
      activated protein kinase (p38 MAPK). Our findings give the evidence that beta
      escin sodium might have potential anti-angiogenic activity via its direct effects
      on ECs.

PMID- 18718876
TI  - Performance of the BioPlex 2200 Autoimmune Vasculitis kit.
AB  - The BioRad BioPlex 2200 Vasculitis kit demonstrates excellent relative
      sensitivity and relative specificity for the semi-quantitative detection of IgG
      autoantibodies to MPO, PR3 and GBM. The fully-automated platform simultaneously
      measures three analytes in a single tube, offering superior advantage in speed
      and ease of use over current assays. The availability of a fully-automated
      platform with 24-hour availability for these three antibodies may be of
      considerable value in the differential diagnosis of patients with rapidly
      progressive glomerulonephritis.

PMID- 18718877
TI  - Co-stimulatory modulation in rheumatoid arthritis: the role of (CTLA4-Ig)
      abatacept.
AB  - Associations between rheumatoid arthritis (RA) susceptibility and polymorphism in
      multiple immunoregulatory genes suggest a role of altered T cell function in the
      disease. The growing relevance of the oxidative stress in RA synovitis, which
      results in a number of T cell signalling abnormalities, is reinforced by the
      demonstration of a direct NO inducing activity through the shared epitope of the
      HLA class II molecules HLA-DRbeta1, with secondary lymphocytes oxidative damage.
      Direct T cell/macrophage contact-dependent activation, one of the driving
      mechanisms of synovitis, is mediated by co-stimulatory molecules as well as cell
      membrane cytokines and may also result in an impaired suppressive function of T
      regulatory cells (Treg) in RA joints. The fusion of CTLA4 extracellular binding
      domain to the Fcgamma1 allows to obtain a soluble CTLA4 receptor, the dimeric
      recombinant human fusion protein abatacept (CTLA4-Ig). The improved knowledge of
      the CTLA4-B7 co-stimulation regulatory mechanisms by signals delivered into DCs
      and Tregs provides multiple potential targets for the abatacept treatment. CTLA4
      Ig shows the capacity, either ex vivo or in vivo, to interrupt at multiple steps
      the ongoing inflammatory and destructive process, and to concur in restoring the
      immunoregulatory balance in RA.

PMID- 18718878
TI  - Recent advances in diagnostic technologies for autoimmune diseases.
AB  - The investigation of autoimmunity provides an interest challenge in "omics"
      research and, particularly, proteome research, as autoimmune diseases are common
      disorders of unsolved etiology that occur in a wide range of manifestations, in
      all of which tissues and organs are attacked by the body's own immune system.
      Autoantibodies are a hallmark of many autoimmune diseases and the presence of
      autoantibodies is a distinctive and key characteristic of autoimmune diseases.
      Conventionally, the study of autoimmune response has always been conducted by
      analysing the presence and/or concentration of individual antibodies in
      biological fluids. New proteomic techniques allow the simultaneous
      identification/measurement of different autoantibodies in sera of patients
      suffering from autoimmune diseases. The possibility of simultaneously measuring a
      number of correlated analytes appears to be very interesting for analytical
      reasons (reduced volumes of biological samples, reagents and low costs),
      logistical/managerial reasons, and pathophysiological reasons (combination of
      markers in disease-oriented or organ-oriented profiling). In particular, we
      describe data collected by using high-throughput techniques such as antigen
      microarrays and mass spectrometry for antibody profiling. While recently
      collected data demonstrate satisfactory analytical sensitivity and
      reproducibility, some issues such as standardization and data interpretation have
      to be solved before the introduction of these new and promising techniques into
      clinical practice.

PMID- 18718880
TI  - Sexual relationship power as a mediator between dating violence and sexually
      transmitted infections among college women.
AB  - This study examined relationship power as a possible mediator of the relationship
      between dating violence and sexually transmitted infections (STIs). The proposed
      mediation model was based on the theory of gender and power as well as previous
      research on intimate partner violence and STI risk. Survey results from a sample
      of 290 single, undergraduate women indicated that 85% experienced at least one
      form of dating violence victimization in the past year, 5.9% tested positive for
      an STI, and 5.2% received treatment for an STI. Results revealed that women with
      lower levels of sexual relationship power had higher rates of dating violence
      victimization and STIs; also, sexual relationship power partially mediated the
      relationship between dating violence victimization and STIs. Future dating
      violence and STI-prevention interventions targeting young women may want to use
      an empowerment approach to decrease their likelihood of dating violence
      victimization and STI risk.

PMID- 18718881
TI  - Attitudes toward wife beating: a cross-country study in Asia.
AB  - Using demographic and health surveys conducted between 1998 and 2001 from seven
      countries (Armenia, Bangladesh, Cambodia, India, Kazakhstan, Nepal, and Turkey),
      the study found that acceptance of wife beating ranged from 29% in Nepal, to 57%
      in India (women only), and from 26% in Kazakhstan, to 56% in Turkey (men only).
      Increasing wealth predicted less acceptance of wife beating, except in Cambodia
      and Nepal. Higher education level was negatively associated with acceptance in
      Turkey and Bangladesh. Younger respondents justified wife beating more often,
      with some exceptions, showing persistent intergenerational transmission of gender
      norms. Working women were equally or more likely to justify wife beating compared
      to nonworking women. Men were significantly more likely to justify wife beating
      in Armenia, Nepal, and Turkey. Targeted proactive efforts are needed to change
      these norms, such as improving female literacy rates and other enabling factors.

PMID- 18718879
TI  - Protein modifications in transcription elongation.
AB  - Posttranslational modifications (PTMs) of proteins play essential roles in
      regulating signaling, protein-protein modifications and subcellular localization.
      In this review, we focus on posttranslational modification of histones and RNA
      polymerase II (RNAPII) and their roles in gene transcription. A survey of the
      basic features of PTMs is provided followed by a more detailed account of how
      PTMs on histones and RNAPII regulate transcription in the model organism
      Saccharomyces cerevisiae. We emphasize the interconnections between histone and
      RNAPII PTMs and speculate upon the larger role PTMs have in regulating protein
      function in the cell.

PMID- 18718882
TI  - Mental health correlates of intimate partner violence in marital relationships in
      a nationally representative sample of males and females.
AB  - It is important to understand the epidemiology of intimate partner violence (IPV)
      experienced by both males and females. Data were drawn from the U.S. National
      Comorbidity Survey Replication. The relationships between physical IPV and child
      abuse, mental disorders, and suicidal ideation and attempts among males and
      females were examined. The results indicate that child sexual abuse was
      associated with IPV among males, whereas child physical and sexual abuse was
      associated with IPV among females. IPV was associated with poor mental health
      outcomes for males and females, although sex differences are noted. The sex
      differences indicate that females experience a wider range of poor mental health
      outcomes compared to males. Knowledge about correlates of IPV can be useful in
      identifying individuals exposed to violence. Further research is required to
      identify effective methods to reduce exposure to IPV and to adequately address
      the specific needs of male and female victims of IPV.

PMID- 18718883
TI  - Does adherence to medications for type 2 diabetes differ between individuals with
      vs without schizophrenia?
AB  - Individuals with schizophrenia are at increased risk for poor health outcomes and
      mortality. This may be due to inadequate self-management of co-occurring
      conditions, such as type 2 diabetes. We compared adherence to oral hypoglycemic
      medications for diabetes patients with vs without comorbid schizophrenia. Using
      Veterans Affairs (VA) health system administrative data, we identified all
      patients with both schizophrenia and type 2 diabetes and with at least one oral
      hypoglycemic prescription fill in fiscal year 2002 (N = 11 454) and a comparison
      group of patients with diabetes who were not diagnosed with schizophrenia (N = 10
      560). Nonadherence was operationalized as having a medication possession ratio
      indicating receipt of less than 80% of needed hypoglycemic medications. Poor
      adherence was less prevalent among diabetes patients with (43%) than without
      schizophrenia (52%, P < .001). In multivariable analyses, having schizophrenia
      was associated with a 25% lower likelihood of poor adherence compared with not
      having schizophrenia (adjusted odds ratio: 0.75, 95% confidence interval: 0.70
      0.80). Poorer adherence was associated with black race, homelessness, depression,
      substance use disorder, and medical comorbidity. Having more outpatient visits, a
      higher proportion of prescriptions delivered by mail, lower prescription
      copayments, and more complex medication regimens were each associated with
      increased adherence. Among veterans with diabetes receiving ongoing VA care,
      overall hypoglycemic medication adherence was low, but individuals with comorbid
      schizophrenia were more likely to be adherent to these medications. Future
      studies should investigate whether factors such as comanagement of a chronic
      psychiatric illness or regular contact with mental health providers bestow
      benefits for diabetes self-management in persons with schizophrenia.

PMID- 18718884
TI  - A randomized controlled trial of cognitive remediation in schizophrenia.
AB  - Individuals with schizophrenia have consistently been found to exhibit cognitive
      deficits, which have been identified as critical mediators of psychosocial
      functional outcomes. Recent reviews of cognitive remediation (CRT) have concluded
      that these deficits respond to training. This multi-site community study examined
      40 individuals with schizophrenia who underwent cognitive remediation using the
      Neuropsychological Educational Approach to Remediation(1) (NEAR). Assessments
      using the same neuropsychological tests and measures of psychosocial outcome were
      made at four time points: baseline, before start of active intervention, end of
      active intervention and 4 months after end of active intervention. Dose of
      antipsychotic medication remained constant throughout the study period. After
      participating in NEAR, individuals showed significant improvements in verbal and
      visual memory, sustained attention and executive functioning. This effect
      persisted 4 months after the treatment ceased. The average effect size was mild
      to moderate. Social and occupational outcomes also improved from baseline to post
      treatment, which persisted 4 months later. Our findings replicate those of
      previous studies that suggest that NEAR is effective in improving cognition in
      individuals with schizophrenia in a naturalistic and ecologically valid setting.
      Further it extends such findings to show a generalisation of effects to
      social/occupational outcomes and persistence of effects in the short term.

PMID- 18718886
TI  - Implementation of locally adapted guidelines on type 2 diabetes.
AB  - OBJECTIVE: To assess the effects of a facilitator enhanced multifaceted
      intervention to implement a locally adapted guideline on the shared care for
      people with type 2 diabetes. METHODS: During 1 year a cluster-randomized trial
      was performed in 30 general practices. In the intervention group, nurse
      facilitators enhanced guideline implementation by analysing barriers to change,
      introducing structured care, training practice staff and giving performance
      feedback. Targets for HbA1c%, systolic blood pressure as well as indications for
      angiotensin converting enzyme/angiotensin receptor blocking agent prescription
      differed from the national guidelines. In the control group, GPs were asked to
      continue the care for people with diabetes as usually. Generalized estimating
      equations were used to control for the clustered design of the study. RESULTS: In
      the intervention group, more people were seen on a 3-monthly basis (88% versus
      69%, P < 0.001) and more blood pressure and bodyweight measurements were
      performed every 3 months (blood pressure 83% versus 66%, P < 0.001 and bodyweight
      78.9% versus 48.5%, P < 0.001). Apart from a marginal difference in mean
      cholesterol, differences in HbA1c%, blood pressure, body mass index and treatment
      satisfaction were not significant. CONCLUSION: Multifaceted implementation of
      locally adapted shared care guidelines did improve the process of diabetes care
      but hardly changed intermediate outcomes. In the short term, local adaptation of
      shared care guidelines does not improve the cardiovascular risks of people with
      type 2 diabetes.

PMID- 18718887
TI  - Heartlift patients? An interview-based study of GP trainers and the impact of
      'patients they like'.
AB  - BACKGROUND: The concept of the 'heartsink patient' is well known and much used
      when talking about general practice. The opposite of this type of patient,
      however, has been little explored. OBJECTIVE: To identify patient characteristics
      valued by GPs. METHODS: Structured interview to collect narratives from GPs of
      individual patients, analysed qualitatively through thematic analysis and word
      frequency. SETTING: Primary Care in Ireland. PARTICIPANTS: GP trainers. MAIN
      OUTCOME MEASURES: Emergent themes from four lead questions: Tell me about a
      patient you like, Tell me about the patient's personality, What have you learned
      about yourself as a GP?, What is different about being a GP as opposed to any
      other kind of doctor? In addition, a corpus linguistic analysis of word
      frequencies disclosed further themes, not identifiable on the surface of
      discourse. RESULTS: Ten themes were identified: GPs valued patients who were
      likeable, a challenge, involved them in negotiation of the doctor-patient
      relationship, were interesting or virtuous and had a positive effect. GPs valued
      their profession in that they were facilitators, gave and elicited loyalty,
      formed personal attachments and had a different perspective. CONCLUSIONS:
      'Heartlift patients' may be a robust concept, to counterbalance heartsink
      patients. Data collected are suitable for training, and could help GPs enhance a
      sense of vocation.

PMID- 18718885
TI  - Psychosocial stress and psychosis. A review of the neurobiological mechanisms and
      the evidence for gene-stress interaction.
AB  - This article presents evidence suggesting that psychosocial stress may increase
      risk for psychosis, especially in the case of cumulative exposure. A
      heuristically useful framework to study the underlying mechanisms is the concept
      of "behavioral sensitization" that stipulates that exposure to psychosocial
      stress--such as life events, childhood trauma, or discriminatory experiences--may
      progressively increase the behavioral and biological response to subsequent
      exposures. The neurobiological substrate of sensitization may involve
      dysregulation of the hypothalamus-pituitary-adrenal axis, contributing to a
      hypothesized final common pathway of dopamine sensitization in mesolimbic areas
      and increased stress-induced striatal dopamine release. It is argued that, in
      order to reconcile genetic and environmental influences on the development of
      psychosis, gene-environment interactions may be an important mechanism in
      explaining between-subject differences in risk following (cumulative) exposure to
      psychosocial stress. To date, most studies suggestive of gene-stress interaction
      have used proxy measures for genetic vulnerability such as a family history of
      psychosis; studies investigating interactions between molecular genetic measures
      and psychosocial stressors are still relatively scarce. Preliminary evidence
      suggests that polymorphisms within the catechol-O-methyltransferase and brain
      derived neurotrophic factor genes may interact with psychosocial stress in the
      development of psychosis; however, extensive further investigations are required
      to confirm this.

PMID- 18718888
TI  - Bone marrow histology in marginal zone B-cell lymphomas: correlation with
      clinical parameters and flow cytometry in 120 patients.
AB  - BACKGROUND: Among marginal zone lymphomas (MZLs), bone marrow (BM) involvement
      features are well established in the splenic marginal zone lymphoma (SMZL); few
      data are available for extranodal marginal zone lymphoma (EMZL) and nodal
      marginal zone lymphoma (NMZL). PATIENTS AND METHODS: Incidence and patterns of
      histologic BM involvement are studied in 120 MZL patients (48 SMZL, 59 EMZL, 13
      NMZL) at onset and during follow-up; relationships between clinical features, BM
      histology and flow cytometry (FC) are analyzed. RESULTS: At diagnosis, BM
      involvement occurs in 90% SMZL, 22% EMZL and 54% NMZL (P<0.0001); at
      reevaluation, incidence raises to 96% in SMZL and 34% in EMZL. Concordance
      between histology and FC is found in 87% of cases; most discordant cases have
      positive histology but negative FC. SMZL and EMZL show a nodular BM infiltration;
      the interstitial pattern is frequent in NMZL (P<0.0001); sinusoidal localization
      is typical of SMZL, frequent in NMZL and occasional in EMZL (P=0.0001). Stage,
      leukemic disease, B symptoms, more than one extranodal involved site,
      splenomegaly, elevated beta2-microglobulin, serum monoclonal component,
      International Prognostic Index (IPI) and age-adjusted IPI are directly related to
      BM infiltration. CONCLUSIONS: The different prevalence of BM involvement in MZL
      subtypes reflects their heterogeneous dissemination modalities; histology seems
      more sensible than FC to detect BM infiltration; development of BM involvement
      during follow-up is typical of EMZL.

PMID- 18718889
TI  - Development and daily use of an electronic oncological patient record for the
      total management of cancer patients: 7 years' experience.
AB  - BACKGROUND: We describe our experience with an electronic oncological patient
      record (EOPR) for the total management of cancer patients. METHODS: The web-based
      EOPR was developed on the basis of a user-centred design including user education
      and training, followed by continuous assistance; user acceptance was monitored by
      means of three questionnaires administered after 2 weeks, 6 months and 6 years.
      RESULTS: The EOPR has been used daily for all in-ward, day hospital and
      ambulatory clinical activities since July 2000. The most widely appreciated
      functions are its rapid multipoint access, the self-updated summary of the
      patients' clinical course, the management of the entire therapeutic programme
      synchronised with working agendas and oncological teleconsultation. Security and
      privacy are assured by means of the separate storage of clinical and demographic
      data, with access protected by login and a password. The questionnaires
      highlighted appreciation of rapid data retrieval and exchange and the perception
      of improved quality of care, but also revealed a sense of additional work and a
      negative impact on doctor-patient relationships. CONCLUSIONS: Our EOPR has proved
      to be effective in the total management of cancer patients. Its user-centred
      design and flexible web technology have been key factors in its successful
      implementation and daily use.

PMID- 18718890
TI  - Childhood cancer in Japan: focusing on trend in mortality from 1970 to 2006.
AB  - OBJECTIVE: This paper describes the mortality rates and trends from childhood
      cancer at the population level over a 37-year period in Japan and other developed
      countries. MATERIALS AND METHODS: Age-standardized mortality rates were
      calculated by the direct method using age-specific mortality rates at 5-year age
      intervals and weights based on the age distribution of the standard world
      population. The joinpoint regression model was used to describe changes in
      trends. RESULTS: For all cancers combined, the mortality rate during 2000-2006
      was 2.20 per 100,000 population for boys and 1.89 for girls. Mortality for all
      cancers combined decreased since 1970s in Japan. A stable trend was observed in
      recent 5 years for girls. For leukemia, a declining trend was observed in the
      whole period for girls and in 1976-2006 for boys. Mortality rates for childhood
      central nervous system tumors have remained stable at a low level during 1980
      2006. CONCLUSIONS: The present study provides updated figures and trends in
      childhood cancer mortality in Japan and other developed countries. This will help
      to estimate care needs and to plan intervention and the quantity of appropriate
      childhood cancer treatment.

PMID- 18718891
TI  - Eligibility for concurrent chemotherapy and radiotherapy of locally advanced lung
      cancer patients: a prospective, population-based study.
AB  - BACKGROUND: Patients with stage III non-small-cell lung cancer (NSCLC) and
      limited disease small-cell lung cancer are excluded from concurrent
      chemoradiation mostly on the basis of comorbidity and age. The purpose of this
      prospective study was to get insight in what proportion of patients with locally
      advanced lung cancer would be suitable for concurrent chemoradiation. PATIENTS
      AND METHODS: From 2002 to 2005, all patients with a pathological diagnosis of
      lung cancer and with locally advanced disease in the Maastricht Cancer Registry,
      the Netherlands, comorbidity were prospectively assessed. Patients were regarded
      as noneligible for concurrent chemoradiation if they had one or more important
      comorbidity or were 75 years or older. RESULTS: In all, 711 patients were
      included, 577 with NSCLC and 134 with SCLC. Overall, 166 patients (23.3%) were 75
      years or older. Of the 526 patients <75 years, comorbidities were as follows: 278
      (52.9%) 0, 188 (35.7%) 1, and 56 (11.4%) 2 or more. In all, 408/686 (59%) of the
      whole patient group were considered as ineligible for concurrent chemoradiation.
      CONCLUSIONS: More than half of patients with stage III lung cancer were
      theoretically not eligible for concurrent chemoradiation. Less toxic alternatives
      are needed for these patients.

PMID- 18718892
TI  - Randomized study of weekly irinotecan plus high-dose 5-fluorouracil (FUIRI)
      versus biweekly irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI) as first-line
      chemotherapy for patients with metastatic colorectal cancer: a Spanish
      Cooperative Group for the Treatment of Digestive Tumors Study.
AB  - BACKGROUND: Irinotecan plus infusional 5-fluorouracil/leucovorin (FOLFIRI) is
      accepted as a reference treatment for the first-line treatment of patients with
      metastatic colorectal cancer (MCRC). The aim of this study was to demonstrate
      that a regimen without leucovorin (LV) (FUIRI) is not inferior to the standard
      FOLFIRI (response rate). PATIENTS AND METHODS: Chemotherapy-naive patients with
      MCRC were randomized to receive either irinotecan (180 mg/m(2) on day 1) + 5
      fluorouracil (5-FU) (400 mg/m(2) bolus and 600 mg/m(2) 22-h infusion) + LV (200
      mg/m(2) on days 1-2) (FOLFIRI) every 2 weeks or irinotecan (80 mg/m(2)) + 5-FU
      (2.250 mg/m(2) 48-h infusion) (FUIRI) weekly. RESULTS: In all, 346 patients were
      included, 173 in each arm. In the intention-to-treat analysis, the response rates
      for FOLFIRI and FUIRI were 57% [95% confidence interval (CI) 49% to 64%] and 51%
      (95% CI 43% to 59%), respectively (P = 0.2809). No statistically significant
      differences were observed between FOLFIRI and FUIRI regarding median progression
      free survival (8.3 versus 8.4 months; P = 0.4339) nor median overall survival
      (21.6 versus 19.2 months; log-rank test P = 0.2941). Grade 3/4 neutropenia was
      significantly more frequent on FOLFIRI arm (27% versus 9%), while the proportion
      of diarrhea was higher on FUIRI arm (21% versus 42%). CONCLUSION: FUIRI
      represents a valid alternative without LV to the FOLFIRI regimen as MCRC first
      line treatment.

PMID- 18718895
TI  - Determination of lifetime injury mortality risk in Canada in 2002 by drinking
      amount per occasion and number of occasions.
AB  - Injury is the leading cause of alcohol-attributable mortality in Canada. Risk is
      determined by amount consumed per occasion and accumulates across drinking
      episodes. The authors estimated alcohol-attributable injury mortality in Canada
      for 2002 by combining the absolute risk of injury unrelated to alcohol with
      relative risks that were specific to gender and consumption per occasion, while
      taking into account lifetime number of drinking occasions. The absolute risk
      increased as number of drinking occasions and number of drinks per occasion
      increased. The absolute risk remained relatively low at fewer than 2 drinking
      occasions per month, regardless of number of drinks. Absolute risk levels reached
      1 in 1,000 at 5 or more drinks once per month for men and at 5-7 drinks once per
      month for women. The probability of mortality was 1 in 100 for all levels of
      consumption above 3 drinks 3 times per week for men and above 5 drinks 3 times
      per week for women. No safe level of consumption is recommended based on these
      results, although risk is much lower for consuming 3 standard drinks or less
      fewer than 3 times per week. Absolute risk reflects long-term effects of drinking
      patterns and is important for risk-communication and alcohol-control policy.

PMID- 18718894
TI  - Changes in alcohol-related mortality and its socioeconomic differences after a
      large reduction in alcohol prices: a natural experiment based on register data.
AB  - The authors examined the effect of a large reduction in the price of alcohol in
      Finland in 2004 on alcohol-related mortality by age and socioeconomic group. For
      this register-based study of Finns aged >or=15 years, data on independent
      variables were extracted from the employment statistics of Statistics Finland.
      Mortality follow-up was carried out for 2001-2003 (before the price reduction)
      and 2004-2005 (after). Alcohol-related causes were defined using both underlying
      and contributory causes of death. Alcohol-related mortality increased by 16%
      among men and by 31% among women; 82% of the increase was due to chronic causes,
      particularly liver diseases. The increase in absolute terms was largest among men
      aged 55-59 years and women aged 50-54 years. Among persons aged 30-59 years, it
      was biggest among the unemployed or early-age pensioners and those with low
      education, social class, or income. The relative differences in change between
      the education and social class subgroups were small. The employed and persons
      aged <35 years did not suffer from increased alcohol-related mortality during the
      2 years after the change. These results imply that a large reduction in the price
      of alcohol led to substantial increases in alcohol-related mortality,
      particularly among the less privileged, and in chronic diseases associated with
      heavy drinking.

PMID- 18718897
TI  - Linking exposure to polychlorinated biphenyls with fatty fish consumption and
      reduced fetal growth among Danish pregnant women: a cause for concern?
AB  - In a selected group of women from the Danish National Birth Cohort, the authors
      investigated the association between intake of fatty fish and plasma
      concentrations of polychlorinated biphenyls (PCBs) on the one hand and the
      association between maternal PCB concentrations and fetal growth on the other. Of
      70,183 women who filled in a food frequency questionnaire during 1996-2002, 100
      nulliparous women aged 25-35 years with normal prepregnancy body mass index were
      selected according to their intake of fatty fish (low (0 meals/month, n = 34),
      medium (1-3 meals/month, n = 33), or high (> or = meals/month, n = 33)). Women
      with a high intake of fatty fish had 50% (95% confidence interval (CI): 31, 72)
      higher plasma PCB concentrations than women with low intake. Maternal plasma PCB
      concentrations were inversely associated with birth weight and placental weight.
      The adjusted mean difference between the 75th and 25th PCB percentiles was -155 g
      (95% CI: -291, -19) for birth weight and -81 g (95% CI: -135, -26) for placental
      weight. These results support previous findings from this cohort, where fatty
      fish intake was inversely associated with fetal growth. Dietary recommendations
      often encourage weekly consumption of fatty fish. These results suggest that
      potential exposure to PCBs should be carefully considered before recommending
      such intakes among women of childbearing age.

PMID- 18718898
TI  - Expression of stathmin, a microtubule regulatory protein, is associated with the
      migration and differentiation of cultured early trophoblasts.
AB  - BACKGROUND: The microtubule-destabilizing protein stathmin is expressed by the
      villous cytotrophoblasts and invasive extravillous trophoblasts (EVTs) in the
      first-trimester human placenta. Here, we evaluated the significance of stathmin
      expression in terms of the functions of trophoblasts. METHODS: We employed two
      choriocarcinoma cell lines (BeWo and JEG-3), an EVT cell line (HTR-8/SVneo) and
      isolated first-trimester trophoblast cells. The effects of small-interfering (si)
      RNA-mediated stathmin knockdown on trophoblast proliferation and migration were
      measured by WST-1 and Transwell assays, respectively. Trophoblast differentiation
      was induced by dibutyryl (db)-cAMP treatment and evaluated by measuring human
      chorionic gonadotrophin beta (hCGbeta) and syncytin expression and cell fusion.
      We examined the effect of knockdown and induced stathmin expression on db-cAMP
      induced differentiation. RESULTS: siRNA-induced silencing of stathmin expression
      had a marked inhibitory effect on BeWo, JEG-3 and HTR-8/SVneo cell migration and
      also suppressed their proliferation, albeit to a lesser extent. db-cAMP-enhanced
      hCGbeta and syncytin expression and cell fusion in BeWo cells was inhibited by
      stathmin knockdown. However, induced expression of stathmin reversed the hCGbeta
      and syncytin expression and cell fusion in the Tet-On BeWo cells. Suppression of
      stathmin expression also inhibited the migration of and hCGbeta production by
      first-trimester trophoblasts. CONCLUSIONS: Stathmin expression may be closely
      associated with early trophoblast migration and differentiation into
      syncytiotrophoblasts during placentation.

PMID- 18718899
TI  - Impact of compensation on work outcome of carpal tunnel syndrome.
AB  - BACKGROUND: Work-related carpal tunnel syndrome (CTS) is a complex and costly
      condition. There is some evidence that the employment outcome may be worse in
      cases of CTS where the condition is being considered for compensation. AIM: To
      examine whether workers' compensation status is an important determinant of
      outcome of CTS. METHODS: Cases, with a Workers' Compensation Board (WCB) claim,
      and referents, in work but without a WCB claim, were identified from the practice
      of a single specialist physician. Data on history prior to and at the time of
      diagnosis, and events since diagnosis, were collected from clinical records and
      by a telephone-administered questionnaire. Prior events, severity, treatment and
      outcome associated with a WCB claim were assessed by logistic regression.
      RESULTS: Interviews were successfully completed for 46 cases and 50 referents. In
      the model adjusted only for age and gender, claimants had a worse outcome in
      terms of changing job or stopping work with time loss from work due to CTS [odds
      ratio (OR) 5.1, 95% confidence interval (CI) 1.9-13.3]. The OR was much
      influenced by the inclusion of treatment in the model (OR = 9.6, 95% CI 1.6-58.6)
      with WCB cases more likely to have surgical and physiotherapy treatments. Cases
      with a WCB claim cost more to treat and reported greater loss in income than
      those not seeking compensation. CONCLUSIONS: Although these data are limited, the
      results are suggestive of poorer outcome among WCB claimants despite greater use
      of treatment and comparable severity of disease.

PMID- 18718900
TI  - Audit of pre-placement assessments undertaken in an NHS Trust.
AB  - INTRODUCTION: A high percentage of potential employees are passed fit for work
      despite undergoing pre-placement health assessments. Few studies have evaluated
      the cost effectiveness of such assessments. The aim of this study was to audit
      the outcome of National Health Service (NHS) pre-placement health assessments and
      estimate the manpower costs of undertaking them at an NHS Trust. METHODS: An
      audit of the outcome of NHS pre-placement assessments at an NHS Trust between 1
      April 2005 and 31 March 2006 was undertaken using an electronic database. The
      cost of undertaking the assessments was also calculated based on manpower hours
      spent per year. RESULTS: A total of 2973 pre-placement assessments were
      undertaken during the 12-month period. Of the employees, 98.5% were passed fit
      without comment, 1.5% were passed 'fit with comments' on the fit slip and no
      potential employee was found unfit for NHS work. Ten diagnostic categories
      contributed to a fit with comments result. The manpower cost to this trust per
      year to process the 2973 NHS assessments was estimated to be approximately pounds
      13,502. CONCLUSION: Given the annual financial costs incurred and the high
      percentage of employees passed fit for work, alternative pre-placement health
      assessment methods could be considered. The method should ensure, however, that
      the ability to detect a wide range of medical conditions at the pre-placement
      stage still exists.

PMID- 18718901
TI  - Do occupational health assessments match guidelines for low back pain?
AB  - BACKGROUND: Audit is an important facet of clinical governance and good
      occupational health practice. There are well-established clinical guidelines for
      the management of low back pain. Occupational Health Guidelines for the
      Management of Low Back Pain at Work were launched by the Faculty of Occupational
      Medicine in March 2000, based on an extensive, systematic review of the
      scientific literature predominantly from occupational settings or concerning
      occupational outcomes. AIM: To determine whether documented National Health
      Service occupational health assessment of low back pain in the North West region
      of England conforms to the published guidelines. METHODS: A retrospective audit
      of case notes was conducted. Six performance indicators were derived from the
      Occupational Health Guidelines for the Management of Low Back Pain at Work in
      order to evaluate the performance by occupational physicians. Two hundred and
      seventy-seven case notes were identified from eight different occupational health
      departments. RESULTS: Low rates of compliance with national standards were
      observed for recording of some performance indicators, notably for the assessment
      and documentation of 'red' and 'yellow flags'. Our findings suggest that the
      quality of documentation of key information in the notes leaves significant room
      for improvement. CONCLUSIONS: For future audits, we recommend having two external
      auditors and seek to demonstrate a high degree of agreement between observers by
      conducting a reproducibility exercise. Future Faculty guidelines should emphasize
      documentation of the assessment and perhaps consider assessment tools to improve
      documentation.

PMID- 18718902
TI  - Visual function and fitness to drive.
AB  - INTRODUCTION: Driving is recognized to be a visually intensive task and
      accordingly there is a legal minimum standard of vision required for all
      motorists. The purpose of this paper is to review the current United Kingdom (UK)
      visual requirements for driving and discuss the evidence base behind these legal
      rules. The role of newer, alternative tests of visual function that may be better
      indicators of driving safety will also be considered. Finally, the implications
      of ageing on driving ability are discussed. SOURCES OF DATA: A search of Medline
      and PubMed databases was performed using the following keywords: driving, vision,
      visual function, fitness to drive and ageing. In addition, papers from the
      Department of Transport website and UK Royal College of Ophthalmologists
      guidelines were studied. AREAS OF AGREEMENT, AREAS OF CONTROVERSY, GROWING
      POINTS, AREAS TIMELY FOR DEVELOPING RESEARCH: Current UK visual standards for
      driving are based upon historical concepts, but recent advances in technology
      have brought about more sophisticated methods for assessing the status of the
      binocular visual field and examining visual attention. These tests appear to be
      better predictors of driving performance. Further work is required to establish
      whether these newer tests should be incorporated in the current UK visual
      standards when examining an individual's fitness to drive.

PMID- 18718904
TI  - Acyl-CoA:lysophospholipid acyltransferases.
AB  - Cell membranes contain several classes of glycerophospholipids, which have
      numerous structural and functional roles in the cells. Polyunsaturated fatty
      acids, including arachidonic acid and eicosapentaenoic acid, are located at the
      sn-2 (but not sn-1)-position of glycerophospholipids in an asymmetrical manner.
      Using acyl-CoAs as donors, glycerophospholipids are formed by a de novo pathway
      (Kennedy pathway) and modified by a remodeling pathway (Lands' cycle) to generate
      membrane asymmetry and diversity. Both pathways were reported in the 1950s.
      Whereas enzymes involved in the Kennedy pathway have been well characterized,
      including enzymes in the 1-acylglycerol-3-phosphate O-acyltransferase family,
      little is known about enzymes involved in the Lands' cycle. Recently, several
      laboratories, including ours, isolated enzymes working in the remodeling pathway.
      These enzymes were discovered not only in the 1-acylglycerol-3-phosphate O
      acyltransferase family but also in the membrane-bound O-acyltransferase family.
      In this review, we summarize recent studies on cloning and characterization of
      lysophospholipid acyltransferases that contribute to membrane asymmetry and
      diversity.

PMID- 18718903
TI  - Follistatin-like 1, a secreted muscle protein, promotes endothelial cell function
      and revascularization in ischemic tissue through a nitric-oxide synthase
      dependent mechanism.
AB  - Myogenic Akt signaling coordinates blood vessel recruitment with normal tissue
      growth. Here, we investigated the role of Follistatin-like 1 (Fstl1) in the
      regulation of endothelial cell function and blood vessel growth in muscle.
      Transgenic Akt1 overexpression in skeletal muscle led to myofiber growth that was
      coupled to an increase in muscle capillary density. Myogenic Akt signaling or
      ischemic hind limb surgery led to the induction of Fstl1 in muscle and increased
      circulating levels of Fstl1. Intramuscular administration of an adenoviral vector
      expressing Fstl1 (Ad-Fstl1) accelerated flow recovery and increased capillary
      density in the ischemic hind limbs of wild-type mice, and this was associated
      with an increase in endothelial nitric oxide synthase (eNOS) phosphorylation at
      residue Ser-1179. In cultured endothelial cells, Ad-Fstl1 stimulated migration
      and differentiation into network structures and inhibited apoptosis under
      conditions of serum deprivation. These cell responses were associated with the
      activating phosphorylation of Akt and eNOS. Conversely, transduction with
      dominant-negative Akt or LY294002 blocked Fstl1-stimulated eNOS phosphorylation
      and inhibited Fstl1-stimulated cellular responses. Treatment with the eNOS
      inhibitor N(G)-nitro-L-arginine methyl ester also reduced endothelial cell
      migration and differentiation induced by Ad-Fstl1. The stimulatory effect of Ad
      Fstl1 on ischemic limb reperfusion was abolished in mice lacking eNOS. These data
      indicate that Fstl1 is a secreted muscle protein or myokine that can function to
      promote endothelial cell function and stimulates revascularization in response to
      ischemic insult through its ability to activate Akt-eNOS signaling.

PMID- 18718905
TI  - Leptin stimulates both JAK2-dependent and JAK2-independent signaling pathways.
AB  - Leptin controls body weight by activating the long form of the leptin receptor
      (LEPRb). Janus kinase 2 (JAK2) is associated with LEPRb and autophosphorylates in
      response to leptin. JAK2 also phosphorylates LEPRb, STAT3, and multiple other
      downstream molecules. Surprisingly, here we show that JAK2 is not required for
      leptin stimulation of STAT3 phosphorylation. Leptin time- and dose-dependently
      stimulated tyrosine phosphorylation of STAT3 in both human and mouse JAK2-null
      cells. Leptin also increased the viability of JAK2-null cells. Overexpression of
      c-Src or Fyn, two Src family members, promoted STAT3 phosphorylation, whereas
      inhibition of the endogenous Src family members by either pharmacological
      inhibitors or dominant negative Src(K298M) decreased the ability of leptin to
      stimulate the phosphorylation of STAT3 and ERK1/2. Leptin also stimulated
      tyrosine phosphorylation of kinase-inactive JAK2(K882E) in JAK2-null cells.
      Overexpression of JAK2(K882E) enhanced the ability of leptin to stimulate STAT3
      phosphorylation in JAK2-null cells. Tyr1138 in LEPRb was required for leptin
      stimulated phosphorylation of STAT3 but not JAK2(K882E). These data suggest that
      leptin stimulates non-JAK2 tyrosine kinase(s), including the Src family members,
      which phosphorylate JAK2, STAT3, and other molecules downstream of LEPRb. JAK2
      mediates leptin signaling by both phosphorylating its substrates and forming a
      signaling complex as a scaffolding/adaptor protein. The non-JAK2 kinase(s) and
      JAK2 may act coordinately and synergistically to mediate leptin response.

PMID- 18718906
TI  - Targeted induction of lung endothelial cell apoptosis causes emphysema-like
      changes in the mouse.
AB  - Pulmonary gas exchange relies on a rich capillary network, which, together with
      alveolar epithelial type I and II cells, form alveolar septa, the functional
      units in the lung. Alveolar capillary endothelial cells are critical in
      maintaining alveolar structure, because disruption of endothelial cell integrity
      underlies several lung diseases. Here we show that targeted ablation of lung
      capillary endothelial cells recapitulates the cellular events involved in
      cigarette smoke-induced emphysema, one of the most prevalent nonneoplastic lung
      diseases. Based on phage library screening on an immortalized lung endothelial
      cell line, we identified a lung endothelial cell-binding peptide, which
      preferentially homes to lung blood vessels. This peptide fused to a proapoptotic
      motif specifically induced programmed cell death of lung endothelial cells in
      vitro as well as targeted apoptosis of the lung microcirculation in vivo. As
      early as 4 days following peptide administration, mice developed air space
      enlargement associated with enhanced oxidative stress, influx of macrophages, and
      up-regulation of ceramide. Given that these are all critical elements of the
      corresponding human emphysema caused by cigarette smoke, these data provide
      evidence for a central role for the alveolar endothelial cells in the maintenance
      of lung structure and of endothelial cell apoptosis in the pathogenesis of
      emphysema-like changes. Thus, our data enable the generation of a convenient
      mouse model of human emphysema. Finally, combinatorial screenings on immortalized
      cells followed by in vivo targeting establishes an experimental framework for
      discovery and validation of additional ligand-directed pharmacodelivery systems.

PMID- 18718907
TI  - Structural, functional, and mutational analysis of the NblA protein provides
      insight into possible modes of interaction with the phycobilisome.
AB  - The enormous macromolecular phycobilisome antenna complex (>4 MDa) in
      cyanobacteria and red algae undergoes controlled degradation during certain forms
      of nutrient starvation. The NblA protein (approximately 6 kDa) has been
      identified as an essential component in this process. We have used structural,
      biochemical, and genetic methods to obtain molecular details on the mode of
      action of the NblA protein. We have determined the three-dimensional structure of
      the NblA protein from both the thermophilic cyanobacterium Thermosynechococcus
      vulcanus and the mesophilic cyanobacterium Synechococcus elongatus sp. PCC 7942.
      The NblA monomer has a helix-loop-helix motif which dimerizes into an open, four
      helical bundle, identical to the previously determined NblA structure from
      Anabaena. Previous studies indicated that mutations to NblA residues near the C
      terminus impaired its binding to phycobilisome proteins in vitro, whereas the
      only mutation known to affect NblA function in vivo is located near the protein N
      terminus. We performed random mutagenesis of the S. elongatus nblA gene which
      enabled the identification of four additional amino acids crucial for NblA
      function in vivo. This data shows that essential amino acids are not confined to
      the protein termini. We also show that expression of the Anabaena nblA gene
      complements phycobilisome degradation in an S. elongatus NblA-null mutant despite
      the low homology between NblAs of these cyanobacteria. We propose that the NblA
      interacts with the phycobilisome via "structural mimicry" due to similarity in
      structural motifs found in all phycobiliproteins. This suggestion leads to a new
      model for the mode of NblA action which involves the entire NblA protein.

PMID- 18718908
TI  - Leishmania donovani peroxin 14 undergoes a marked conformational change following
      association with peroxin 5.
AB  - The import of PTS1 proteins into the glycosome or peroxisome requires binding of
      a PTS1-laden PEX5 receptor to the membrane-associated protein PEX14 to facilitate
      translocation of PTS1 proteins into the lumen of these organelles. Quaternary
      structure analysis of protozoan parasite Leishmania donovani PEX14 (LdPEX14)
      revealed that this protein forms a homomeric complex with a size > 670 kDa.
      Moreover, deletion mapping indicated that disruption of LdPEX14 oligomerization
      correlated with the elimination of the hydrophobic region and coiled-coil motif
      present in LdPEX14. Analysis of the LdPEX5-LdPEX14 interaction by isothermal
      titration calorimetry revealed a molar binding stoichiometry of 1:4 (LdPEX5:
      LdPEX14) and an in-solution dissociation constant (K(d)) of approximately 74 nm.
      Calorimetry, circular dichroism, intrinsic fluorescence, and analytical
      ultracentrifugation experiments showed that binding of LdPEX5 resulted in a
      dramatic conformational change in the LdPEX14 oligomeric complex that involved
      the reorganization of the hydrophobic segment in LdPEX14. Finally, limited
      tryptic proteolysis assays established that in the presence of LdPEX5, LdPEX14
      became more susceptible to proteolytic degradation consistent with this protein
      interaction triggering a significant conformational change in the recombinant and
      native LdPEX14 structures. These structural changes provide essential clues to
      how LdPEX14 functions in the translocation of folded proteins across the
      glycosomal membrane.

PMID- 18718909
TI  - Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1
      promotes metabolic switch and drug resistance.
AB  - The switch of cellular metabolism from mitochondrial respiration to glycolysis is
      the hallmark of cancer cells and associated with tumor malignancy. However, the
      mechanism of this metabolic switch remains largely unknown. Herein, we reported
      that hypoxia-inducible factor-1 (HIF-1) induced pyruvate dehydrogenase kinase-3
      (PDK3) expression leading to inhibition of mitochondrial respiration. Promoter
      activity assay, small interference RNA knockdown assay, and chromatin
      immunoprecipitation assay demonstrated that hypoxia-induced PDK3 gene activity
      was regulated by HIF-1 at the transcriptional level. Forced expression of PDK3 in
      cancer cells resulted in increased lactic acid accumulation and drugs resistance,
      whereas knocking down PDK3 inhibited hypoxia-induced cytoplasmic glycolysis and
      cell survival. These data demonstrated that increased PDK3 expression due to
      elevated HIF-1alpha in cancer cells may play critical roles in metabolic switch
      during cancer progression and chemoresistance in cancer therapy.

PMID- 18718910
TI  - Dehydroepiandrosterone stimulates phosphorylation of FoxO1 in vascular
      endothelial cells via phosphatidylinositol 3-kinase- and protein kinase A
      dependent signaling pathways to regulate ET-1 synthesis and secretion.
AB  - Dehydroepiandrosterone (DHEA) is an endogenous adrenal steroid hormone with
      controversial actions in humans. We previously reported that DHEA has opposing
      actions in endothelial cells to stimulate phosphatidylinositol (PI) 3
      kinase/Akt/endothelial nitric-oxide synthase leading to increased production of
      nitric oxide while simultaneously stimulating MAPK-dependent secretion of the
      vasoconstrictor ET-1. In the present study we hypothesized that DHEA may
      stimulate PI 3-kinase-dependent phosphorylation of FoxO1 in endothelial cells to
      help regulate endothelial function. In bovine or human aortic endothelial cells
      (BAEC and HAEC), treatment with DHEA (100 nM) acutely enhanced phosphorylation of
      FoxO1. DHEA-stimulated phosphorylation of FoxO1 was inhibited by pretreatment of
      cells with wortmannin (PI 3-kinase inhibitor) or H89 (protein kinase A (PKA)
      inhibitor) but not ICI182780 (estrogen receptor blocker), or PD98059 (MEK
      (MAPK/extracellular signal-regulated kinase kinase) inhibitor). Small interfering
      RNA knockdown of PKA inhibited DHEA-stimulated phosphorylation of FoxO1. DHEA
      promoted nuclear exclusion of FoxO1 that was blocked by pretreatment of cells
      with wortmannin, H89, or by small interfering RNA knockdown of PKA. DHEA
      treatment of endothelial cells increased PKA activity and intracellular cAMP
      concentrations. Transfection of BAEC with a constitutively nuclear FoxO1 mutant
      transactivated a co-transfected ET-1 promoter luciferase reporter. Treatment of
      BAEC with DHEA inhibited transactivation of the ET-1 promoter reporter in cells
      overexpressing FoxO1. ET-1 promoter activity and secretion in response to DHEA
      treatment was augmented by PI 3-kinase blockade and inhibited by MAPK blockade.
      We conclude that DHEA stimulates phosphorylation of FoxO1 via PI 3-kinase- and
      PKA-dependent pathways in endothelial cells that negatively regulates ET-1
      promoter activity and secretion. Balance between PI 3-kinase-dependent inhibition
      and MAPK-dependent stimulation of ET-1 secretion in response to DHEA may
      determine whether DHEA supplementation improves or worsens cardiovascular and
      metabolic function.

PMID- 18718911
TI  - Epigenetic regulation of HYAL-1 hyaluronidase expression. identification of HYAL
      1 promoter.
AB  - HYAL-1 (hyaluronoglucosaminidase-1) belongs to the hyaluronidase family of
      enzymes that degrade hyaluronic acid. HYAL-1 is a marker for cancer diagnosis and
      a molecular determinant of tumor growth, invasion, and angiogenesis. The
      regulation of HYAL-1 expression is unknown. Real time reverse transcription-PCR
      using 11 bladder and prostate cancer cells and 69 bladder tissues showed that
      HYAL-1 mRNA levels are elevated 10-30-fold in cells/tissues that express high
      hyaluronidase activity. Although multiple transcription start sites (TSS) for
      HYAL-1 mRNA were detected in various tissues, the major TSS in many tissues,
      including bladder and prostate, was at nucleotide 27274 in the cosmid clone
      LUCA13 (AC002455). By analyzing the 1532 base sequence 5' to this TSS, using
      cloning and luciferase reporter assays, we identified a TACAAA sequence at
      position -31 and the minimal promoter region between nucleotides -93 and -38.
      Mutational analysis identified that nucleotides -73 to -50 (which include
      overlapping binding consensus sites for SP1, Egr-1, and AP-2), bases C(-71) and
      C(-59), and an NFkappaB-binding site (at position -15) are necessary for promoter
      activity. The chromatin immunoprecipitation assay identified that Egr-1, AP-2,
      and NFkappaB bind to the promoter in HYAL-1-expressing cells, whereas SP1 binds
      to the promoter in non-HYAL-1-expressing cells. 5-Aza-2'-deoxycytidine treatment,
      bisulfite DNA sequencing, and methylation-specific PCR revealed that HYAL-1
      expression is regulated by methylation at C(-71) and C(-59); both Cs are part of
      the SP1/Egr-1-binding sites. Thus, HYAL-1 expression is epigenetically regulated
      by the binding of different transcription factors to the methylated and
      unmethylated HYAL-1 promoter.

PMID- 18718912
TI  - Flavonoids redirect PIN-mediated polar auxin fluxes during root gravitropic
      responses.
AB  - The rate, polarity, and symmetry of the flow of the plant hormone auxin are
      determined by the polar cellular localization of PIN-FORMED (PIN) auxin efflux
      carriers. Flavonoids, a class of secondary plant metabolites, have been suspected
      to modulate auxin transport and tropic responses. Nevertheless, the identity of
      specific flavonoid compounds involved and their molecular function and targets in
      vivo are essentially unknown. Here we show that the root elongation zone of
      agravitropic pin2/eir1/wav6/agr1 has an altered pattern and amount of flavonol
      glycosides. Application of nanomolar concentrations of flavonols to pin2 roots is
      sufficient to partially restore root gravitropism. By employing a quantitative
      cell biological approach, we demonstrate that flavonoids partially restore the
      formation of lateral auxin gradients in the absence of PIN2. Chemical
      complementation by flavonoids correlates with an asymmetric distribution of the
      PIN1 protein. pin2 complementation probably does not result from inhibition of
      auxin efflux, as supply of the auxin transport inhibitor N-1-naphthylphthalamic
      acid failed to restore pin2 gravitropism. We propose that flavonoids promote
      asymmetric PIN shifts during gravity stimulation, thus redirecting basipetal
      auxin streams necessary for root bending.

PMID- 18718913
TI  - Sequence differences in the IQ motifs of CaV1.1 and CaV1.2 strongly impact
      calmodulin binding and calcium-dependent inactivation.
AB  - The proximal C terminus of the cardiac L-type calcium channel (Ca(V)1.2) contains
      structural elements important for the binding of calmodulin (CaM) and calcium
      dependent inactivation, and exhibits extensive sequence conservation with the
      corresponding region of the skeletal L-type channel (Ca(V)1.1). However, there
      are several Ca(V)1.1 residues that are both identical in six species and are non
      conservatively changed from the corresponding Ca(V)1.2 residues, including three
      of the "IQ motif." To investigate the functional significance of these residue
      differences, we used native gel electrophoresis and expression in intact myotubes
      to compare the binding of CaM to extended regions (up to 300 residues) of the C
      termini of Ca(V)1.1 and Ca(V)1.2. We found that in the presence of Ca(2+) (either
      millimolar or that in resting myotubes), CaM bound strongly to C termini of
      Ca(V)1.2 but not of Ca(V)1.1. Furthermore, replacement of two residues (Tyr(1657)
      and Lys(1662)) within the IQ motif of a C-terminal Ca(V)1.2 construct with the
      divergent residues of Ca(V)1.1 (His(1532) and Met(1537)) led to a weakening of
      CaM binding (native gels), whereas the reciprocal substitution in Ca(V)1.1 caused
      a gain of CaM binding. In full-length Ca(V)1.2, substitution of these same two
      divergent residues with those of Ca(V)1.1 (Y1657H, K1662M) eliminated calcium
      dependent inactivation of the heterologously expressed channel. Thus, our results
      reveal that a conserved difference between the IQ motifs of Ca(V)1.2 and Ca(V)1.1
      has a profound effect on both CaM binding and calcium-dependent inactivation.

PMID- 18718914
TI  - 15-deoxy-Delta(12,14)-prostaglandin J2 induces vascular endothelial cell
      apoptosis through the sequential activation of MAPKS and p53.
AB  - 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a potent anti-angiogenic
      factor and induces endothelial cell apoptosis, although the mechanism remains
      unclear. In this study, 15d-PGJ(2) was found to increase p53 levels of the human
      umbilical vein endothelial cells by stabilizing p53. Both 15d-PGJ(2)-induced
      apoptosis and the induction of p21(Waf1) and Bax can be abolished by p53 small
      interfering RNA but not by peroxisome proliferator-activated receptor gamma
      inhibitors. Moreover, 15d-PGJ(2) activated JNK and p38 MAPK while inducing p53
      phosphorylation at sites responsible for p53 activity. JNK inhibitor (SP600125)
      or p38 MAPK inhibitor (SB203580) pretreatment attenuated 15d-PGJ(2)-mediated
      apoptosis and suppressed the p21(Waf1) and Bax expressions without affecting p53
      protein accumulation. Pretreatment with SP600125 partially prevented the
      phosphorylation of p53 at serines 33 and 392 induced by 15d-PGJ(2). 15d-PGJ(2)
      was also found to induce reactive oxygen species generation and partially blocked
      nuclear factor-kappaB activity. Pretreatment with antioxidant N-acetylcysteine
      prevented the p53 accumulation, the phosphorylations of JNK and p38 MAPK, the
      inhibition of NF-kappaB activity, as well as the apoptosis induced by 15d-PGJ(2).
      Using a mouse model of corneal neovascularization, it was demonstrated in vivo
      that 15d-PGJ(2) induced reactive oxygen species generation, activated JNK and p38
      MAPK, induced p53 accumulation/phosphorylation, and induced vascular endothelial
      cell apoptosis, which could be abolished by N-acetylcysteine, SP600125, SB203580,
      or a virus-derived amphipathic peptides-based p53 small interfering RNA. This is
      the first study that 15d-PGJ(2) induces vascular endothelial cell apoptosis
      through the signaling of JNK and p38 MAPK-mediated p53 activation both in vitro
      and in vivo, further establishing the potential of 15d-PGJ(2) as an anti
      angiogenesis agent.

PMID- 18718915
TI  - Microcephalin/MCPH1 associates with the Condensin II complex to function in
      homologous recombination repair.
AB  - Microcephalin/MCPH1 is one of the causative genes responsible for the autosomal
      recessive disorder primary microcephaly. Patients with this disease present with
      mental retardation and dramatic reduction in head size, and cells derived from
      these patients contain abnormally condensed chromosomes. MCPH1 contains an N
      terminal BRCT and tandem C-terminal BRCT domains. More recently, MCPH1 has been
      implicated in the cellular response to DNA damage; however, the exact mechanism
      remains unclear. Here, we report the identification Condensin II as a major MCPH1
      interacting protein. MCPH1 and Condensin II interact in vivo, mediated by the
      CAPG2 subunit of Condensin II binding to a middle domain (residues 376-485) of
      MCPH1. Interestingly, while Condensin II is not required for the IR-induced G2/M
      checkpoint, Condensin II-depleted cells have a defect in HR repair, which is also
      present in MCPH1(-/-)MEFs. Moreover, the Condensin II binding region of MCPH1 is
      also required for HR function. Collectively, we have identified a novel function
      of MCPH1 to modulate HR repair through Condensin II, and thereby maintain genome
      integrity.

PMID- 18718916
TI  - In vivo and in vitro studies of a functional peroxisome proliferator-activated
      receptor gamma response element in the mouse pdx-1 promoter.
AB  - We reported that peroxisome proliferator-activated receptor gamma (PPARgamma)
      transcriptionally regulates the beta-cell differentiation factor pancreatic
      duodenal homeobox (PDX)-1 based on in vitro RNA interference studies. We have now
      studied mice depleted of PPARgamma within the pancreas (PANC PPARgamma(-/-))
      created by a Cre/loxP recombinase system, with Cre driven by the pdx-1 promoter.
      Male PANC PPARgamma(-/-) mice were hyperglycemic at 8 weeks of age (8.1+/-0.2 mM
      versus 6.4+/-0.3 mM, p=0.009) with islet cytoarchitecture and pancreatic mass of
      islet beta-cells that were indistinguishable from the controls. Islet PDX-1 mRNA
      (p=0.001) and protein levels (p=0.003) were lowered 60 and 40%, respectively, in
      tandem with impaired glucose-induced insulin secretion and loss of
      thiazolidinedione-induced increase in PDX-1 expression. We next identified a
      putative PPAR-response element (PPRE) in the mouse pdx-1 promoter with
      substantial homology to the corresponding region of the human PDX-1 promoter.
      Electrophoretic mobility supershift assays with nuclear extracts from beta-cell
      lines and mouse islets, also in vitro translated PPARgamma and retinoid X
      receptor, and chromatin immunoprecipitation analysis demonstrated specific
      binding of PPARgamma and retinoid X receptor to the human and mouse pdx-1 x
      PPREs. Transient transfection assays of beta-cells with reporter constructs of
      mutated PPREs showed dramatically reduced pdx-1 promoter activity. In summary, we
      have presented in vivo and in vitro evidence showing PPARgamma regulation of pdx
      1 transcription in beta-cells, plus our results support an important regulatory
      role for PPARgamma in beta-cell physiology and thiazolidinedione pharmacology of
      type 2 diabetes.

PMID- 18718917
TI  - Adaptive evolution in rodent seminal vesicle secretion proteins.
AB  - Proteins involved in reproductive fitness have evolved unusually rapidly across
      diverse groups of organisms. These reproductive proteins show unusually high
      rates of amino acid substitutions, suggesting that the proteins have been subject
      to positive selection. We sought to identify seminal fluid proteins experiencing
      adaptive evolution because such proteins are often involved in sperm competition,
      host immunity to pathogens, and manipulation of female reproductive physiology
      and behavior. We performed an evolutionary screen of the mouse prostate
      transcriptome for genes with elevated evolutionary rates between mouse and rat.
      We observed that secreted rodent prostate proteins evolve approximately twice as
      fast as nonsecreted proteins, remarkably similar to findings in the primate
      prostate and in the Drosophila male accessory gland. Our screen led us to
      identify and characterize a group of seminal vesicle secretion (Svs) proteins and
      to show that the gene Svs7 is evolving very rapidly, with many amino acid sites
      under positive selection. Another gene in this group, Svs5, showed evidence of
      branch-specific selection in the rat. We also found that Svs7 is under selection
      in primates and, by using three-dimensional models, demonstrated that the same
      regions have been under selection in both groups. Svs7 has been identified as
      mouse caltrin, a protein involved in sperm capacitation, the process responsible
      for the timing of changes in sperm activity and behavior, following ejaculation.
      We propose that the most likely explanation of the adaptive evolution of Svs7
      that we have observed in rodents and primates stems from an important function in
      sperm competition.

PMID- 18718918
TI  - Alternative splicing and the steady-state ratios of mRNA isoforms generated by it
      are under strong stabilizing selection in Caenorhabditis elegans.
AB  - Evolutionary studies indicate that a high proportion of alternative splicing (AS)
      events are species-specific; just 28% of minor-form alternatively spliced exons
      are conserved between mice and humans. We employed a splicing-sensitive
      microarray to study the evolution of allele-specific AS in nematodes. We compared
      splicing levels among five distinct Caenorhabditis elegans lines. Our results
      indicate that AS is less variable between natural isolates (NIs) from England,
      Hawaii, and Australia than when compared with mutation accumulation lines (6% vs.
      21%, respectively, vary compared with N2). This suggests that strong stabilizing
      selection shapes the evolution of the ratios of isoforms generated by AS in C.
      elegans. When we analyzed some of the splicing changes between the NIs, we found
      examples of changes in both cis and trans that lead to alterations in gene
      specific AS. This indicates that both these mechanisms for changing AS are
      employed along the path toward speciation in nematodes.

PMID- 18718919
TI  - Positive selection in ASPM is correlated with cerebral cortex evolution across
      primates but not with whole-brain size.
AB  - The rapid increase of brain size is a key event in human evolution. Abnormal
      spindle-like microcephaly associated (ASPM) is discussed as a major candidate
      gene for explaining the exceptionally large brain in humans but ASPM's role
      remains controversial. Here we use codon-specific models and a comparative
      approach to test this candidate gene that was initially identified in Homo-chimp
      comparisons. We demonstrate that accelerated evolution of ASPM (omega = 4.7) at
      16 amino acid sites occurred in 9 primate lineages with major changes in relative
      cerebral cortex size. However, ASPM's evolution is not correlated with major
      changes in relative whole-brain or cerebellum sizes. Our results suggest that a
      single candidate gene such as ASPM can influence a specific component of the
      brain across large clades through changes in a few amino acid sites. We
      furthermore illustrate the power of using continuous phenotypic variability
      across primates to rigorously test candidate genes that have been implicated in
      the evolution of key human traits.

PMID- 18718920
TI  - Gene duplications and losses within the cyclooxygenase family of teleosts and
      other chordates.
AB  - Cyclooxygenase (COX) produces prostaglandins in animals via the oxidation and
      reduction of arachidonic acid. Different types and numbers of COX genes have been
      found in corals, sea squirts, fishes, and tetrapods, but no study has used a
      comparative phylogenetic approach to investigate the evolutionary history of this
      complex gene family. Therefore, to examine COX evolution in the teleosts and
      chordates, 9 novel COX sequences (possessing residues and domains critical to COX
      function) were acquired from the euryhaline killifish, longhorn sculpin, sea
      lamprey, Atlantic hagfish, and amphioxus using standard polymerase chain reaction
      (PCR) and cloning methods. Phylogenetic analyses of these and other COX sequences
      show a complicated history of COX duplications and losses. There are three main
      lineages of COX in the chordates corresponding to the three subphyla in the
      phylum Chordata, with each lineage representing an independent COX duplication.
      Hagfish and lamprey most likely have traditional COX-1/2 genes, suggesting that
      these genes originated with the first round of genome duplication in the
      vertebrates according to the 2R hypothesis and are not exclusively present in the
      gnathostomes. All teleosts examined have three COX genes due to a teleost
      specific genome duplication followed by variable loss of a COX-1 (in the
      zebrafish and rainbow trout) or COX-2 gene (in the derived teleosts). Future
      studies should examine the functional ramifications of these differential gene
      losses.

PMID- 18718921
TI  - Lipid-soluble smoke particles upregulate vascular smooth muscle ETB receptors via
      activation of mitogen-activating protein kinases and NF-kappaB pathways.
AB  - Cigarette smoke is a strong risk factor for cardiovascular disease. However, the
      underlying molecular mechanisms that lead to cigarette smoke-associated
      cardiovascular disease remain elusive. With functional and molecular methods, we
      demonstrate for the first time that lipid-soluble cigarette smoke particles
      (dimethylsulfoxide-soluble cigarette smoke particles; DSP) increased the
      expression of endothelin type B (ET(B)) receptors in arterial smooth muscle
      cells. The increased ET(B) receptors in arterial smooth muscle cells was
      documented as enhanced contractility (sensitive myograph technique), elevated
      levels of ET(B) receptor mRNA (quantitative real-time PCR), and protein
      expressions (immunohistochemistry and Western blotting). Intracellular signaling
      was studied with Western blotting and phosphoELISA; this revealed that DSP
      induced extracellular-regulated protein kinases 1 and 2 (ERK1/2), p38, and
      nuclear factor-kappaB (NF-kappaB) phosphorylation within 3 h. Blocking ERK1/2,
      p38, or NF-kappaB activation by their specific inhibitors significantly
      attenuated the DSP-induced upregulation of ET(B) receptor-mediated contraction
      and both ET(B) receptor mRNA and protein expression. In addition, dexamethasone
      abolished the DSP-induced upregulation of ET(B) receptor-mediated contraction. In
      conclusion, upregulation of ET(B) receptors by DSP in arterial smooth muscle
      cells involves activation of mitogen-activating protein kinases (ERK1/2 and p38)
      and the downstream transcriptional factor NF-kappaB pathways.

PMID- 18718923
TI  - Re: Insights into latent class analysis of diagnostic test performance.

PMID- 18718924
TI  - Optimising recruitment into a study of physical activity in older people: a
      randomised controlled trial of different approaches.
AB  - BACKGROUND: physical activity studies in older people often have poor
      recruitment. Including a questionnaire with the invitation would provide
      information about non-participants and selection bias, but could reduce
      recruitment. Telephone contact might encourage participation. OBJECTIVE: to test
      the effects of different strategies for recruitment into a study of physical
      activity in older people. DESIGN: factorial randomised controlled trial.
      Randomisation by household into four groups: telephone contact plus
      questionnaire, telephone contact only, questionnaire only, neither. SETTING:
      primary care, Oxfordshire, United Kingdom. PARTICIPANTS: 560 patients > or = 65
      years randomly selected after exclusions. INTERVENTIONS: questionnaire to assess
      health, functional ability and physical activity. Telephone contact by the
      research nurse a week after sending study information. MAIN OUTCOME MEASURE:
      recruitment into physical activity study. RESULTS: telephone contact increased
      recruitment: contact 47.9% (134/280), no contact 37.9% (106/280), difference
      (adjusted for the clustering effect of household) 10.0% (95% CI 0.2-19.8).
      Questionnaire inclusion did not significantly reduce recruitment: no
      questionnaire 44.3% (124/280) questionnaire 41.4% (116/280) difference -2.9% (95%
      CI -12.7-7.0). CONCLUSIONS: telephone contact significantly increased recruitment
      and should be considered in studies where recruitment may be low. While inclusion
      of a questionnaire provided valuable information on non-participants and did not
      significantly reduce recruitment, an adverse recruitment effect could not be
      excluded.

PMID- 18718925
TI  - Cell type differences in activity of the Streptomyces bacteriophage phiC31
      integrase.
AB  - Genomic integration by the Streptomyces bacteriophage C31 integrase is a
      promising tool for non-viral gene therapy of various genetic disorders. We
      investigated the C31 integrase recombination activity in T cell derived cell
      lines, primary T lymphocytes and CD34(+) haematopoietic stem cells in comparison
      to mesenchymal stem cells and cell lines derived from lung-, liver- and cervix
      tissue. In T cell lines, enhanced long-term expression above control was observed
      only with high amounts of integrase mRNA. Transfections of C31 integrase plasmids
      were not capable of mediating enhanced long-term transgene expression in T cell
      lines. In contrast, moderate to high efficiency could be detected in human
      mesenchymal stem cells, human lung, liver and cervix carcinoma cell lines. Up to
      100-fold higher levels of recombination product was found in C31 integrase
      transfected A549 lung than Jurkat T cells. When the C31 integrase activity was
      normalized to the intracellular integrase mRNA levels, a 16-fold difference was
      found. As one possible inhibitor of the C31 integrase, we found 3- to 5-fold
      higher DAXX levels in Jurkat than in A549 cells, which could in addition to other
      yet unknown factors explain the observed discrepancy of C31 integrase activity.

PMID- 18718926
TI  - Core flexibility of a truncated metazoan mitochondrial tRNA.
AB  - Secondary and tertiary structures of tRNAs are remarkably preserved from bacteria
      to humans, the notable exception being the mitochondrial (m) tRNAs of metazoans,
      which often deviate substantially from the canonical cloverleaf (secondary) or
      'L'-shaped (tertiary) structure. Many metazoan mtRNAs lack either the TpsiC (T)
      or dihydrouridine (D) loops of the canonical cloverleaf, which are known to
      confer structural rigidity to the folded structure. Thus, the absence of
      canonical TpsiC-D interactions likely results in greater dispersion of anticodon
      acceptor interstem angle than for canonical tRNAs. To test this hypothesis, we
      have assessed the dispersion of the anticodon-acceptor angle for bovine
      mtRNA(Ser)(AGY), which lacks the canonical D arm and is thus incapable of forming
      stabilizing interarm interactions. Using the method of transient electric
      birefringence (TEB), and by changing the helical torsion angle between a core
      mtRNA bend and a second bend of known angle/rigidity, we have demonstrated that
      the core of mtRNA(Ser)(AGY) has substantially greater flexibility than its well
      characterized canonical counterpart, yeast cytoplasmic tRNA(Phe). These results
      suggest that increased flexibility, in addition to a more open interstem angle,
      would allow both noncanonical and canonical mtRNAs to utilize the same protein
      synthetic apparatus.

PMID- 18718928
TI  - DNA methylation determination by liquid chromatography-tandem mass spectrometry
      using novel biosynthetic [U-15N]deoxycytidine and [U-15N]methyldeoxycytidine
      internal standards.
AB  - Methylation of the promoter CpG regions regulates gene transcription by
      inhibiting transcription factor binding. Deoxycytidine methylation may regulate
      cell differentiation, while aberrations in the process may be involved in cancer
      etiology and the development of birth defects (e.g. neural tube defects).
      Similarly, nutritional deficiency and certain nutragenomic interactions are
      associated with DNA hypomethylation. While LC-MS has been used previously to
      measure percentage genomic deoxycytidine methylation, a lack of a secure source
      of internal standards and the need for laborious and time-consuming DNA digestion
      protocols constitute distinct limitations. Here we report a simple and
      inexpensive protocol for the biosynthesis of internal standards from readily
      available precursors. Using these biosynthetic stable-isotopic [U-(15)N]-labeled
      internal standards, coupled with an improved DNA digestion protocol developed in
      our lab, we have developed a low-cost, high-throughput (>500 samples in 4 days)
      assay for measuring deoxycytidine methylation in genomic DNA. Inter- and
      intraassay variation for the assay (%RSD, n = 6) was <2.5%.

PMID- 18718927
TI  - Viral AlkB proteins repair RNA damage by oxidative demethylation.
AB  - Bacterial and mammalian AlkB proteins are iron(II)- and 2-oxoglutarate-dependent
      dioxygenases that reverse methylation damage, such as 1-methyladenine and 3
      methylcytosine, in RNA and DNA. An AlkB-domain is encoded by the genome of
      numerous single-stranded, plant-infecting RNA viruses, the majority of which
      belong to the Flexiviridae family. Our phylogenetic analysis of AlkB sequences
      suggests that a single plant virus might have acquired AlkB relatively recently,
      followed by horizontal dissemination among other viruses via recombination. Here,
      we describe the first functional characterization of AlkB proteins from three
      plant viruses. The viral AlkB proteins efficiently reactivated methylated
      bacteriophage genomes when expressed in Escherichia coli, and also displayed
      robust, iron(II)- and 2-oxoglutarate-dependent demethylase activity in vitro.
      Viral AlkB proteins preferred RNA over DNA substrates, and thus represent the
      first AlkBs with such substrate specificity. Our results suggest a role for viral
      AlkBs in maintaining the integrity of the viral RNA genome through repair of
      deleterious methylation damage, and support the notion that AlkB-mediated RNA
      repair is biologically relevant.

PMID- 18718922
TI  - HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical
      isolates to the integrase inhibitors raltegravir and elvitegravir in vitro.
AB  - OBJECTIVES: We investigated the in vitro phenotypic susceptibility of HIV-2
      isolates from integrase inhibitor (INI)-naive patients to INIs and its relation
      to HIV-2 integrase gene polymorphism. METHODS: We determined the phenotypic
      susceptibility to raltegravir and elvitegravir of co-cultured isolates obtained
      from the HIV-2 ROD reference strain and from 14 clinical isolates. IC(50) values
      were compared with those for HIV-1 reference strains. HIV-2 integrase gene
      polymorphism was assessed in isolates from 52 INI-naive patients enrolled in the
      French HIV-2 cohort. RESULTS: Median raltegravir and elvitegravir IC(50) values
      for the 14 clinical HIV-2 isolates were 2.4 and 0.7 nM, respectively, and were
      similar to those observed for HIV-2 ROD and HIV-1 reference strains. Overall, 38%
      of HIV-2 integrase amino acids were polymorphic. The catalytic triad DDE and the
      HHCC and RKK motifs were fully conserved, at the same genomic positions as
      described in HIV-1. In subtype B isolates, the total length of the integrase gene
      varied, owing to the presence of stop codons at positions 288, 294, 297 and 302.
      Fourteen of the positions associated with substitutions conferring INI resistance
      in HIV-1 were polymorphic in HIV-2. CONCLUSIONS: Despite 40% heterogeneity
      between the HIV-1 and HIV-2 integrase genes, the phenotypic susceptibility of
      clinical HIV-2 isolates to INIs was similar to that of HIV-1. This new class of
      antiretroviral drugs thus represents a novel therapeutic possibility for HIV-2
      infected patients who otherwise have few treatment options.

PMID- 18718929
TI  - DNA base flipping by both members of the PspGI restriction-modification system.
AB  - The PspGI restriction-modification system recognizes the sequence CCWGG. R.PspGI
      cuts DNA before the first C in the cognate sequence and M.PspGI is thought to
      methylate N4 of one of the cytosines in the sequence. M.PspGI enhances
      fluorescence of 2-aminopurine in DNA if it replaces the second C in the sequence,
      while R.PspGI enhances fluorescence when the fluorophore replaces adenine in the
      central base pair. This strongly suggests that the methyltransferase flips the
      second C in the recognition sequence, while the endonuclease flips both bases in
      the central base pair out of the duplex. M.PspGI is the first N4-cytosine MTase
      for which biochemical evidence for base flipping has been presented. It is also
      the first type IIP methyltransferase whose catalytic activity is strongly
      stimulated by divalent metal ions. However, divalent metal ions are not required
      for its base-flipping activity. In contrast, these ions are required for both
      base flipping and catalysis by the endonuclease. The two enzymes have similar
      temperature profiles for base flipping and optimal flipping occurs at
      temperatures substantially below the growth temperature of the source organism
      for PspGI and for the catalytic activity of endonuclease. We discuss the
      implications of these results for DNA binding by these enzymes and their
      evolutionary origin.

PMID- 18718930
TI  - Biochemical analysis of the N-terminal domain of human RAD54B.
AB  - The human RAD54B protein is a paralog of the RAD54 protein, which plays important
      roles in homologous recombination. RAD54B contains an N-terminal region outside
      the SWI2/SNF2 domain that shares less conservation with the corresponding region
      in RAD54. The biochemical roles of this region of RAD54B are not known, although
      the corresponding region in RAD54 is known to physically interact with RAD51. In
      the present study, we have biochemically characterized an N-terminal fragment of
      RAD54B, consisting of amino acid residues 26-225 (RAD54B(26-225)). This fragment
      formed a stable dimer in solution and bound to branched DNA structures. RAD54B(26
      225) also interacted with DMC1 in both the presence and absence of DNA. Ten DMC1
      segments spanning the entire region of the DMC1 sequence were prepared, and two
      segments, containing amino acid residues 153-214 and 296-340, were found to
      directly bind to the N-terminal domain of RAD54B. A structural alignment of DMC1
      with the Methanococcus voltae RadA protein, a homolog of DMC1 in the helical
      filament form, indicated that these RAD54B-binding sites are located near the ATP
      binding site at the monomer-monomer interface in the DMC1 helical filament. Thus,
      RAD54B binding may affect the quaternary structure of DMC1. These observations
      suggest that the N-terminal domain of RAD54B plays multiple roles of in
      homologous recombination.

PMID- 18718933
TI  - Rice peptide deformylase PDF1B is crucial for development of chloroplasts.
AB  - Because protein synthesis begins with N-formylmethionine in plant endosymbiotic
      organelles, removal of the formyl group by peptide deformylase (PDF) is essential
      to allowing the excision of the first methionine. Rice contains three copies
      (OsPDF1A, OsPDF1B and OsPDF1B2) of the PDF genes. Unlike OsPDF1A and OsPDF1B,
      OsPDF1B2 is apparently non-functional, with several deleterious substitutions and
      deletions. OsPDF1A is more strongly expressed in the roots, while OsPDF1B is
      expressed at higher levels in mature leaves. Transient expression of PDF-green
      fluorescent protein (GFP) fusion proteins in the protoplasts demonstrates that,
      unlike OsPDF1A, OsPDF1B is localized in both the chloroplasts and the
      mitochondria. We used T-DNA insertional alleles to elucidate functional roles
      associated with OsPDF1B. Homozygous plants of pdf1b/pdf1b exhibited the
      phenotypes of chlorina and growth retardation. Histochemical analysis showed that
      the length of their mesophyll cells was increased 4- to 5-fold, resulting in a
      reduction in the total number of cells. Transmission electron microscopy analyses
      revealed that chloroplasts were severely damaged and mitochondria appeared to be
      mildly altered in the pdf1b mutants. Expression of genes encoded in the
      chloroplasts and mitochondria was altered in the mutants. Based on these results,
      we conclude that OsPDF1B is essential for the development of chloroplast and
      perhaps mitochondria.

PMID- 18718934
TI  - The glycerophosphoryl diester phosphodiesterase-like proteins SHV3 and its
      homologs play important roles in cell wall organization.
AB  - Despite the importance of extracellular events in cell wall organization and
      biogenesis, the mechanisms and related factors are largely unknown. We isolated
      an allele of the shaven3 (shv3) mutant of Arabidopsis thaliana, which exhibits
      ruptured root hair cells during tip growth. SHV3 encodes a novel protein with two
      tandemly repeated glycerophosphoryl diester phosphodiesterase-like domains and a
      glycosylphosphatidylinositol anchor, and several of its paralogs are found in
      Arabidopsis. Here, we report the detailed characterization of mutants of SHV3 and
      one of its paralogs, SVL1. The shv3 and svl1 double mutant exhibited additional
      defects, including swollen guard cells, aberrant expansion of the hypocotyl
      epidermis and ectopic lignin deposits, suggesting decreased rigidity of the cell
      wall. Fourier-transform infrared spectroscopy and measurement of the cell wall
      components indicated an altered cellulose content and pectin modification with
      cross-linking in the double mutant. Furthermore, we found that the ruptured root
      hair phenotype of shv3 was suppressed by increasing the amount of borate, which
      is supposed to be involved in pectic polysaccharide cross-linking, in the medium.
      These findings indicate that SHV3 and its paralogs are novel important factors
      involved in primary cell wall organization.

PMID- 18718935
TI  - Arabidopsis thaliana has a set of J proteins in the endoplasmic reticulum that
      are conserved from yeast to animals and plants.
AB  - J domain-containing proteins (J proteins) are functional partners for heat shock
      protein 70 (Hsp70) molecular chaperones and mediate various cellular processes by
      regulating activities of Hsp70. Budding yeast has three J proteins in the
      endoplasmic reticulum (ER): Scj1p and Jem1p functioning in protein folding and
      quality control in the ER, and Sec63p functioning in protein translocation across
      the ER membrane as partners for BiP, an Hsp70 in the ER. Here we report that
      Arabidopsis thaliana has orthologs of these yeast ER J proteins, which we
      designated as AtERdj3A, AtERdj3B, AtP58(IPK), AtERdj2A and AtERdj2B. Tunicamycin
      treatment of Arabidopsis cells, which causes ER stress, led to up-regulation of
      AtERdj3A, AtERdj3B, AtP58(IPK) and AtERdj2B. Subcellular fractionation analyses
      showed their ER localization, indicating that the identified J proteins indeed
      function as partners for BiP in Arabidopsis cells. Since expression of AtERdj3A,
      AtERdj3B and AtP58(IPK) partially suppressed the growth defects of the yeast
      jem1Deltascj1Delta mutant, they have functions similar to those of Scj1p and
      Jem1p. T-DNA insertions of the AtERDJ2A gene resulted in pollen germination
      defects, probably reflecting its essential function in protein translocation.
      These results suggest that A. thaliana has a set of ER J proteins structurally
      and functionally conserved from yeast to plants.

PMID- 18718932
TI  - Comprehensive transcriptome analysis of phytohormone biosynthesis and signaling
      genes in microspore/pollen and tapetum of rice.
AB  - To investigate the involvement of phytohormones during rice microspore/pollen
      (MS/POL) development, endogenous levels of IAA, gibberellins (GAs), cytokinins
      (CKs) and abscisic acid (ABA) in the mature anther were analyzed. We also
      analyzed the global expression profiles of genes related to seven phytohormones,
      namely auxin, GAs, CKs, brassinosteroids, ethylene, ABA and jasmonic acids, in
      MS/POL and tapetum (TAP) using a 44K microarray combined with a laser
      microdissection technique (LM-array analysis). IAA and GA(4) accumulated in a
      much higher amount in the mature anther compared with the other tissues, while
      CKs and ABA did not. LM-array analysis revealed that sets of genes required for
      IAA and GA synthesis were coordinately expressed during the later stages of
      MS/POL development, suggesting that these genes are responsible for the massive
      accumulation of IAA and GA(4) in the mature anther. In contrast, genes for GA
      signaling were preferentially expressed during the early developmental stages of
      MS/POL and throughout TAP development, while their expression was down-regulated
      at the later stages of MS/POL development. In the case of auxin signaling genes,
      such mirror-imaged expression observed in GA synthesis and signaling genes was
      not observed. IAA receptor genes were mostly expressed during the late stages of
      MS/POL development, and various sets of AUX/IAA and ARF genes were expressed
      during the different stages of MS/POL or TAP development. Such cell type-specific
      expression profiles of phytohormone biosynthesis and signaling genes demonstrate
      the validity and importance of analyzing the expression of phytohormone-related
      genes in individual cell types independently of other cells/tissues.

PMID- 18718931
TI  - Stability and kinetics of G-quadruplex structures.
AB  - In this review, we give an overview of recent literature on the structure and
      stability of unimolecular G-rich quadruplex structures that are relevant to drug
      design and for in vivo function. The unifying theme in this review is energetics.
      The thermodynamic stability of quadruplexes has not been studied in the same
      detail as DNA and RNA duplexes, and there are important differences in the
      balance of forces between these classes of folded oligonucleotides. We provide an
      overview of the principles of stability and where available the experimental data
      that report on these principles. Significant gaps in the literature have been
      identified, that should be filled by a systematic study of well-defined
      quadruplexes not only to provide the basic understanding of stability both for
      design purposes, but also as it relates to in vivo occurrence of quadruplexes.
      Techniques that are commonly applied to the determination of the structure,
      stability and folding are discussed in terms of information content and
      limitations. Quadruplex structures fold and unfold comparatively slowly, and DNA
      unwinding events associated with transcription and replication may be operating
      far from equilibrium. The kinetics of formation and resolution of quadruplexes,
      and methodologies are discussed in the context of stability and their possible
      biological occurrence.

PMID- 18718936
TI  - A mouse model for congenital myasthenic syndrome due to MuSK mutations reveals
      defects in structure and function of neuromuscular junctions.
AB  - In the muscle-specific tyrosine kinase receptor gene MUSK, a heteroallelic
      missense and a null mutation were identified in a patient suffering from a
      congenital myasthenic syndrome (CMS). We generated one mouse line carrying the
      homozygous missense mutation V789M in musk (musk(V789M/V789M) mice) and a second
      hemizygous line, resembling the patient genotype, with the V789M mutation on one
      allele and an allele lacking the kinase domain (musk(V789M/-) mice). We report
      here that musk(V789M/V789M) mice present no obvious abnormal phenotype regarding
      weight, muscle function and viability. In contrast, adult musk(V789M/-) mice
      suffer from severe muscle weakness, exhibit shrinkage of pelvic and scapular
      regions and hunchback. Musk(V789M/-) diaphragm develops less force upon direct or
      nerve-induced stimulation. A profound tetanic fade is observed following nerve
      evoked muscle contraction, and fatigue resistance is severely impaired upon a
      train of tetanic nerve stimulations. Electrophysiological measurements indicate
      that fatigable muscle weakness is due to impaired neurotransmission as observed
      in a patient suffering from a CMS. The diaphragm of adult musk(V789M/-) mice
      exhibits pronounced changes in endplate architecture, distribution and
      innervation pattern. Thus, the missense mutation V789M in MuSK acts as a
      hypomorphic mutation and leads to insufficiency in MuSK function in musk(V789M/-)
      mutants. These mutant mice represent valuable models for elucidating the roles of
      MuSK for synapse formation, maturation and maintenance as well as for studying
      the pathophysiology of a CMS due to MuSK mutations.

PMID- 18718937
TI  - Protective role of Engrailed in a Drosophila model of Huntington's disease.
AB  - Huntington's disease (HD) is caused by the expansion of the polyglutamine (polyQ)
      tract in the human Huntingtin (hHtt) protein (polyQ-hHtt). Although this mutation
      behaves dominantly, htt loss of function may also contribute to HD pathogenesis.
      Using a Drosophila model of HD, we found that Engrailed (EN), a transcriptional
      activator of endogenous Drosophila htt (dhtt), is able to prevent aggregation of
      polyQ-hHtt. To interpret these findings, we tested and identified a protective
      role of N-terminal fragments of both Drosophila and Human wild-type Htt onto
      polyQ-hHtt-induced cellular defects. In addition, N-terminal parts of normal hHtt
      were also able to rescue eye degeneration due to the loss of Drosophila
      endogenous dhtt function. Thus, our data indicate that Drosophila and Human Htt
      share biological properties, and confirm a model whereby EN activates endogenous
      dhtt, which in turn prevents polyQ-hHtt-induced phenotypes. The protective role
      of wild-type hHtt N-terminal parts, specifically onto polyQ-hHtt-induced cellular
      toxicity suggests that the HD may be considered as a dominant negative disease
      rather than solely dominant.

PMID- 18718939
TI  - Analyzing gene perturbation screens with nested effects models in R and
      bioconductor.
AB  - Nested effects models (NEMs) are a class of probabilistic models introduced to
      analyze the effects of gene perturbation screens visible in high-dimensional
      phenotypes like microarrays or cell morphology. NEMs reverse engineer
      upstream/downstream relations of cellular signaling cascades. NEMs take as input
      a set of candidate pathway genes and phenotypic profiles of perturbing these
      genes. NEMs return a pathway structure explaining the observed perturbation
      effects. Here, we describe the package nem, an open-source software to
      efficiently infer NEMs from data. Our software implements several search
      algorithms for model fitting and is applicable to a wide range of different data
      types and representations. The methods we present summarize the current state-of
      the-art in NEMs. AVAILABILITY: Our software is written in the R language and
      freely avail-able via the Bioconductor project at http://www.bioconductor.org.

PMID- 18718938
TI  - Epileptic and developmental disorders of the speech cortex: ligand/receptor
      interaction of wild-type and mutant SRPX2 with the plasminogen activator receptor
      uPAR.
AB  - Mutations in SRPX2 (Sushi-Repeat Protein, X-linked 2) cause rolandic epilepsy
      with speech impairment (RESDX syndrome) or with altered development of the speech
      cortex (bilateral perisylvian polymicrogyria). The physiological roles of SRPX2
      remain unknown to date. One way to infer the function of SRPX2 relies on the
      identification of the as yet unknown SRPX2 protein partners. Using a combination
      of interactome approaches including yeast two-hybrid screening, co
      immunoprecipitation experiments, cell surface binding and surface plasmon
      resonance (SPR), we show that SRPX2 is a ligand for uPAR, the urokinase-type
      plasminogen activator (uPA) receptor. Previous studies have shown that uPAR(-/-)
      knock-out mice exhibited enhanced susceptibility to epileptic seizures and had
      brain cortical anomalies consistent with altered neuronal migration and
      maturation, all features that are reminiscent to the phenotypes caused by SRPX2
      mutations. SPR analysis indicated that the p.Y72S mutation associated with
      rolandic epilepsy and perisylvian polymicrogyria, led to a 5.8-fold gain-of
      affinity of SRPX2 with uPAR. uPAR is a crucial component of the extracellular
      plasminogen proteolysis system; two more SRPX2 partners identified here, the
      cysteine protease cathepsin B (CTSB) and the metalloproteinase ADAMTS4, are also
      components of the extracellular proteolysis machinery and CTSB is a well-known
      activator of uPA. The identification of functionally related SRPX2 partners
      provides the first and exciting insights into the possible role of SRPX2 in the
      brain, and suggests that a network of SRPX2-interacting proteins classically
      involved in the proteolytic remodeling of the extracellular matrix and including
      uPAR participates in the functioning, in the development and in disorders of the
      speech cortex.

PMID- 18718941
TI  - Empirical profile mixture models for phylogenetic reconstruction.
AB  - MOTIVATION: Previous studies have shown that accounting for site-specific amino
      acid replacement patterns using mixtures of stationary probability profiles
      offers a promising approach for improving the robustness of phylogenetic
      reconstructions in the presence of saturation. However, such profile mixture
      models were introduced only in a Bayesian context, and are not yet available in a
      maximum likelihood (ML) framework. In addition, these mixture models only perform
      well on large alignments, from which they can reliably learn the shapes of
      profiles, and their associated weights. RESULTS: In this work, we introduce an
      expectation-maximization algorithm for estimating amino acid profile mixtures
      from alignment databases. We apply it, learning on the HSSP database, and observe
      that a set of 20 profiles is enough to provide a better statistical fit than
      currently available empirical matrices (WAG, JTT), in particular on saturated
      data.

PMID- 18718940
TI  - Novel pathway compendium analysis elucidates mechanism of pro-angiogenic
      synthetic small molecule.
AB  - MOTIVATION: Computational techniques have been applied to experimental datasets
      to identify drug mode-of-action. A shortcoming of existing approaches is the
      requirement of large reference databases of compound expression profiles. Here,
      we developed a new pathway-based compendium analysis that couples multi
      timepoint, controlled microarray data for a single compound with systems-based
      network analysis to elucidate drug mechanism more efficiently. RESULTS: We
      applied this approach to a transcriptional regulatory footprint of phthalimide
      neovascular factor 1 (PNF1)-a novel synthetic small molecule that exhibits
      significant in vitro endothelial potency-spanning 1-48 h post-supplementation in
      human micro-vascular endothelial cells (HMVEC) to comprehensively interrogate
      PNF1 effects. We concluded that PNF1 first induces tumor necrosis factor-alpha
      (TNF-alpha) signaling pathway function which in turn affects transforming growth
      factor-beta (TGF-beta) signaling. These results are consistent with our previous
      observations of PNF1-directed TGF-beta signaling at 24 h, including differential
      regulation of TGF-beta-induced matrix metalloproteinase 14 (MMP14/MT1-MMP) which
      is implicated in angiogenesis. Ultimately, we illustrate how our pathway-based
      compendium analysis more efficiently generates hypotheses for compound mechanism
      than existing techniques.

PMID- 18718942
TI  - Seeder: discriminative seeding DNA motif discovery.
AB  - MOTIVATION: The computational identification of transcription factor binding
      sites is a major challenge in bioinformatics and an important complement to
      experimental approaches. RESULTS: We describe a novel, exact discriminative
      seeding DNA motif discovery algorithm designed for fast and reliable prediction
      of cis-regulatory elements in eukaryotic promoters. The algorithm is tested on
      biological benchmark data and shown to perform equally or better than other motif
      discovery tools. The algorithm is applied to the analysis of plant tissue
      specific promoter sequences and successfully identifies key regulatory elements.

PMID- 18718943
TI  - cneViewer: a database of conserved non-coding elements for studies of tissue
      specific gene regulation.
AB  - There are thousands of strongly conserved non-coding elements (CNEs) in
      vertebrate genomes, and their functions remain largely unknown. However, without
      biologically relevant criteria for prioritizing them, selecting a particular CNE
      sequences to study can be haphazard. To address this problem, we present
      cneViewer-a database and webtool that systematizes information on conserved non
      coding DNA elements in zebrafish. A key feature here is the ability to search for
      CNEs that may be relevant to tissue-specific gene regulation, based on known
      developmental expression patterns of nearby genes. cneViewer provides this and
      other organizing features that significantly facilitate experimental design and
      CNE analysis.

PMID- 18718944
TI  - siDRM: an effective and generally applicable online siRNA design tool.
AB  - Small interfering RNAs (siRNAs) have become an indispensable tool for the
      investigation of gene functions. Most existing siRNA design tools were trained on
      datasets assembled from confined origins, incompatible with the diverse siRNA
      laboratory practice to which these tools will ultimately be applied. We have
      performed an updated analysis using the disjunctive rule merging (DRM) approach
      on a large and diverse dataset compiled from siRecords, and implemented the
      resulting rule sets in siDRM, a new online siRNA design tool. siDRM also
      implements a few high-sensitivity rule sets and fast rule sets, links to
      siRecords, and uses several filters to check unwanted detrimental effects,
      including innate immune responses, cell toxic effects and off-target activities
      in selecting siRNAs. A performance comparison using an independent dataset
      indicated that siDRM outperforms 19 existing siRNA design tools in identifying
      effective siRNAs.

PMID- 18718945
TI  - Local coherence in genetic interaction patterns reveals prevalent functional
      versatility.
AB  - MOTIVATION: Epistatic or genetic interactions, representing the effects of
      mutating one gene on the phenotypes caused by mutations in one or more distinct
      genes, can be very helpful for uncovering functional relationships between genes.
      Recently, the epistatic miniarray profiles (E-MAP) method has emerged as a
      powerful approach for identifying such interactions systematically. For E-MAP
      data analysis, hierarchical clustering is used to partition genes into groups on
      the basis of the similarity between their global interaction profiles, and the
      resulting descriptions assign each gene to only one group, thereby ignoring the
      multifunctional roles played by most genes. RESULTS: Here, we present the
      original local coherence detection (LCD) algorithm for identifying groups of
      functionally related genes from E-MAP data in a manner that allows individual
      genes to be assigned to more than one functional group. This enables
      investigation of the pleiotropic nature of gene function. The performance of our
      algorithm is illustrated by applying it to two E-MAP datasets and an E-MAP-like
      in silico dataset for the yeast Saccharomyces cerevisiae. In addition to
      recapitulating the majority of the functional modules and many protein complexes
      reported previously, our algorithm uncovers many recently documented and novel
      multifunctional relationships between genes and gene groups. Our algorithm hence
      represents a valuable tool for uncovering new roles for genes with annotated
      functions and for mapping groups of genes and proteins into pathways.

PMID- 18718946
TI  - Eigen-R2 for dissecting variation in high-dimensional studies.
AB  - We provide a new statistical algorithm and software package called 'eigen-R(2)'
      for dissecting the variation of a high-dimensional biological dataset with
      respect to other measured variables of interest. We apply eigen-R(2) to two real
      life examples and compare it with simply averaging R(2) over many features.
      AVAILABILITY: An R-package eigenR2 is available at
      http://www.genomine.org/eigenr2/ and will be made publicly available via
      Bioconductor.

PMID- 18718947
TI  - Rtreemix: an R package for estimating evolutionary pathways and genetic
      progression scores.
AB  - In genetics, many evolutionary pathways can be modeled by the ordered
      accumulation of permanent changes. Mixture models of mutagenetic trees have been
      used to describe disease progression in cancer and in HIV. In cancer, progression
      is modeled by the accumulation of chromosomal gains and losses in tumor cells; in
      HIV, the accumulation of drug resistance-associated mutations in the viral genome
      is known to be associated with disease progression. From such evolutionary
      models, genetic progression scores can be derived that assign measures for the
      disease state to single patients. Rtreemix is an R package for estimating mixture
      models of evolutionary pathways from observed cross-sectional data and for
      estimating associated genetic progression scores. The package also provides
      extended functionality for estimating confidence intervals for estimated model
      parameters and for evaluating the stability of the estimated evolutionary mixture
      models.

PMID- 18718948
TI  - Multi-dimensional classification of biomedical text: toward automated, practical
      provision of high-utility text to diverse users.
AB  - MOTIVATION: Much current research in biomedical text mining is concerned with
      serving biologists by extracting certain information from scientific text. We
      note that there is no 'average biologist' client; different users have distinct
      needs. For instance, as noted in past evaluation efforts (BioCreative, TREC, KDD)
      database curators are often interested in sentences showing experimental evidence
      and methods. Conversely, lab scientists searching for known information about a
      protein may seek facts, typically stated with high confidence. Text-mining
      systems can target specific end-users and become more effective, if the system
      can first identify text regions rich in the type of scientific content that is of
      interest to the user, retrieve documents that have many such regions, and focus
      on fact extraction from these regions. Here, we study the ability to characterize
      and classify such text automatically. We have recently introduced a multi
      dimensional categorization and annotation scheme, developed to be applicable to a
      wide variety of biomedical documents and scientific statements, while intended to
      support specific biomedical retrieval and extraction tasks. RESULTS: The
      annotation scheme was applied to a large corpus in a controlled effort by eight
      independent annotators, where three individual annotators independently tagged
      each sentence. We then trained and tested machine learning classifiers to
      automatically categorize sentence fragments based on the annotation. We discuss
      here the issues involved in this task, and present an overview of the results.
      The latter strongly suggest that automatic annotation along most of the
      dimensions is highly feasible, and that this new framework for scientific
      sentence categorization is applicable in practice.

PMID- 18718949
TI  - An unsupervised conditional random fields approach for clustering gene expression
      time series.
AB  - MOTIVATION: There is a growing interest in extracting statistical patterns from
      gene expression time-series data, in which a key challenge is the development of
      stable and accurate probabilistic models. Currently popular models, however,
      would be computationally prohibitive unless some independence assumptions are
      made to describe large-scale data. We propose an unsupervised conditional random
      fields (CRF) model to overcome this problem by progressively infusing information
      into the labelling process through a small variable voting pool. RESULTS: An
      unsupervised CRF model is proposed for efficient analysis of gene expression time
      series and is successfully applied to gene class discovery and class prediction.
      The proposed model treats each time series as a random field and assigns an
      optimal cluster label to each time series, so as to partition the time series
      into clusters without a priori knowledge about the number of clusters and the
      initial centroids. Another advantage of the proposed method is the relaxation of
      independence assumptions.

PMID- 18718950
TI  - Left ventricular pseudoaneurysm with infective pericarditis: a rare cause of
      intractable hemoptysis.
AB  - A 52-year-old man with diabetes presented with recurrent, massive hemoptysis
      following pericardiectomy for pyopericardium secondary to Streptococcus viridans
      infection. Chest radiograph and bronchoscopic examinations revealed no bronchial
      cause. Computed tomography of the chest and echocardiography showed a
      pseudoaneurysm of the left ventricle. Surgical exploration confirmed that the
      pseudoaneurysm communicated with the left lung parenchyma and was the cause of
      recurrent intractable hemoptysis.

PMID- 18718952
TI  - The Council of Europe recommendation Rec(2006)7 on management of patient safety
      and prevention of adverse events in health care.

PMID- 18718953
TI  - Bicarbonate buffered ultrafiltration leads to a physiologic priming solution in
      pediatric cardiac surgery.
AB  - Pediatric cardiopulmonary bypass (CPB) involves a high ratio of priming blood
      volume to patient blood volume. The composition of packed red blood cells (RBCs)
      is very unphysiological in terms of acid-base, electrolyte and metabolite values.
      Therefore, we tested the hypothesis whether ultrafiltration of the prime and
      replacement with bicarbonate buffered hemofiltration solution (BB-HS) is
      sufficient for reducing the metabolic load and reaching a physiologic state. For
      planned surgery of congenital heart defects with cardiopulmonary bypass, 20 CPB
      circuits were primed with BB-HS, gelatin and 1 unit of RBCs. The fluid was
      hemofiltrated using an ultrahemofilter at 300 ml/min until approximately 1000 ml
      of ultrafiltrate was restored with BB-HS. Blood gas analyses were obtained from
      the priming blood, once before and once after bicarbonate buffered
      ultrafiltration (BBUF). The measured substrates decreased significantly (P<0.001)
      after BBUF (glucose from 13.0+/-2.6 to 6.3+/-1.0 and lactate from 3.8+/-1.5 to
      2.3+/-1.0 mmol/l). Acid-base parameters increased (P<0.001) to normal or high
      normal values (pH from 7.01+/-0.09 to 7.68+/-0.12; HCO(3) from 12.1+/-2.4 to
      25.4+/-3.6 mmol/l and BE from -15.4+/-3.6 to -0.8+/-3.7 mmol/l). Even the
      electrolytes sodium, potassium and calcium changed significantly (P<0.001) toward
      the physiologic range. BBUF is an efficient method of reducing the metabolic load
      of priming. After BBUF, even the electrolyte and acid-base balance reached a
      physiologic state, which is important for minimizing electrolyte and acid-base
      disturbances after initiation of CPB.

PMID- 18718954
TI  - Vena cava as autologous tissue for pulmonary valve substitute.
AB  - In this study, we report on our first experience with the construction of a valve
      using autologous vena cava tissue for right ventricular outflow tract
      reconstruction. Simulating the clinical situation valves were built from tubular
      pieces of porcine inferior vena cava placed in a PTFE tube and investigated in a
      pulsatile flow simulator. Based on the given vena cava dimensions, conduits were
      constructed with diameters of 19 mm in bicuspid or tricuspid and 22 mm and 24 mm
      in bicuspid configuration. The lowest pressure gradients were observed in the 22
      mm vena cava valves in bicuspid configuration (8.6+/-0.5 mmHg) compared to 24 mm
      valves (10.6+/-0.9 mmHg, P=0.0004) and 19 mm valves (13.4+/-1.5 mmHg, P=0.005).
      No differences could be found between 19 mm bicuspid and tricuspid valves.
      Concerning valve opening movements, a complete opening in the 19 mm and a nearly
      unhindered opening in 22 mm valves were registered. In 24 mm valves opening was
      incomplete. Leakage was increased in 19 mm bicuspid valves due to leaflet
      prolapse. In conclusion, construction of a valve mechanism from vena cava tissue
      is feasible. The in-vitro hemodynamic results are encouraging, animal experiments
      are ongoing to investigate the midterm function of these valves.

PMID- 18718955
TI  - Consequences of incomplete repair of acute type A aortic dissection.
AB  - During emergency repair of acute Stanford type A aortic dissections, surgical
      compromises in the form of incomplete arch replacement are made due to the
      unstable condition of the patient and safety issues of the performing team. We
      report a case of delayed reoperation after previous incomplete surgery for acute
      type A aortic dissection in a young patient with Marfan's syndrome. He presented
      again with repetitive chest pain five years after initial surgical treatment.
      Extensive aneurysmal dilatation of the aorta and remaining dissection led to the
      decision to replace the ascending aorta and the aortic arch. After a good
      progress during the first days after surgery, the patient died due to a ruptured
      thoraco-abdominal aneurysm on the fifth postoperative day. Extensive surgical
      reconstruction including aortic arch replacement should be considered in patients
      with Marfan's syndrome who present with aortic dissections type A to avoid
      unnecessary reoperations and their complications.

PMID- 18718956
TI  - Survey on chest drainage systems adopted in Europe.
AB  - The aim of this survey, promoted by the European Society of Thoracic Surgeons,
      was to acquire information and advice from 'the field' in order to promote
      development of technology for thoracic surgery and to provide information for
      future guidelines on chest drainage. Society members were offered a questionnaire
      on the European Society of Thoracic Surgeons website (November 2006) composed of
      seven sections comprehending 21 detailed items. The questionnaire was completed
      by 120 centres, 100% performed lung surgery, 91.6% mediastinal surgery, 54.1%
      oesophageal surgery, 10% cardiothoracic surgery. The PVC straight drain (mean
      55.9%) and silicon drain (mean 38.4%), water-valve/water suction disposable chest
      drainage collection system (mean 43.4%), one bottle (mean 24.8%), and two bottles
      with suction control (mean 18.2%), were the most frequently used. After
      pneumonectomy 51.2% used a balanced drainage system, 9% periodical
      thoracocentesis, 39.8% others. In 57.5-92% drainage suction was stopped <or=4
      postoperative days and in 8-42.5% >4 postoperative days. In 17.6-60.7% drains
      were removed <or=4 postoperative days and in 39.3-82.4% >4 postoperative days.
      The survey demonstrates a trend toward the use of updated technical devices, high
      consideration of the costs, and clinical practice based on personal preferences.

PMID- 18718958
TI  - De-fragmenting standards.

PMID- 18718957
TI  - Mobility one year after unilateral lower limb amputation: a modern, UK
      institutional report.
AB  - The aim of this current retrospective study was to assess postoperative mobility
      one year after above knee (AKA) or below knee amputation (BKA) in a district
      general hospital. Data on patient demographics, diabetic status, risks for
      peripheral vascular disease, mortality and mobility at one year were recorded
      from the vascular database. Seventy-five patients underwent lower limb amputation
      over a 70-month period (AKA n=31, BKA n=44). Operative mortality was 10% and
      mortality at one year 13.7%. Fourteen out of the 31 patients (45.1%) who
      underwent AKA were mobile independently or with a walking stick compared to 54.5%
      (24/44) in the BKA group (P=0.44). Fifteen patients (48.3%) were diabetic in the
      AKA group compared to 26 patients (59.1%) in the BKA group (P=0.49). In the under
      60 years group and over 60 years group there was no significant difference in
      type of amputation (P=0.64) or mobility (P=0.69). In this current series, there
      was no significant rehabilitation benefits in patients undergoing BKA compared to
      AKA. With an ageing population who inherently have increasing significant medical
      problems, the perceived benefit in preserving the knee joint may not be as
      significant as previously reported.

PMID- 18718959
TI  - Beta radiation exposure of staff during and after therapies with 90Y-labelled
      substances.
AB  - Radioimmunotherapies (RITs) and peptide receptor radiotherapies (PRRTs) with
      (90)Y-labelled compounds offer promising prospects for tumor treatment in nuclear
      medicine. However, when preparing and performing these therapies, which require
      manipulations of high activities of (90)Y (>1 GBq), technicians and physicians
      may receive high exposures, mainly to the skin of the hands. Even non
      occupationally exposed persons, such as caregivers and family members, receive
      external exposures in the initial period after therapy, arising from the (90)Y in
      the patient. The local skin doses of the individual staff members, measured
      during RITs and PRRTs with thermoluminescence detectors fixed with tapes to the
      fingers, vary considerably. The exposure of staff can exceed the annual
      permissible dose limit of 500 mSv if radiation protection standards are low.
      Thus, adequate safety measures are needed. Measurements of the dose rate around
      patients, made using survey meters with sufficient response to beta particles,
      indicate that the exposure of caregivers and family members is considerably
      higher than previously assumed, and was dominated by primary beta radiation
      instead of bremsstrahlung. Nevertheless, under normal circumstances, the annual
      dose limits for the public (effective dose: 1 mSv, skin dose: 50 mSv) will be
      complied with.

PMID- 18718960
TI  - Further progress in the characterisation of complex radiation fields.
AB  - One of the topics which forms part of CONRAD project addresses the problems
      related to the dosimetry of complex-mixed radiation fields at workplaces. This
      topic was included in work package (WP) 6. WP 6 was established to co-ordinate
      research activities in two areas:the development of new techniques and the
      improvement of current techniques for characterisation of complex workplace
      fields (including high-energy fields and pulsed fields): measurement and
      calculation of particle energy and direction distributions (Subgroup A); and
      model improvements for dose assessment of solar particle events (Subgroup B). In
      both cases in order to aid the research, WP 6 increases the efficiency of
      resource utilisation, and facilitates the technology transfer to practical
      application and for the development of standards. This contribution presents a
      general overview of activities of SG A; specific results related to the benchmark
      experiment at GSI Darmstadt are presented separately, and will be published in
      other way. As far as the results acquired in the frame of the SG B activities,
      these are presented in the meeting held as part of EURADOS AM 2008.

PMID- 18718961
TI  - Internal dose assessments: uncertainty studies and update of ideas guidelines and
      databases within CONRAD project.
AB  - The work of Task Group 5.1 (uncertainty studies and revision of IDEAS guidelines)
      and Task Group 5.5 (update of IDEAS databases) of the CONRAD project is
      described. Scattering factor (SF) values (i.e. measurement uncertainties) have
      been calculated for different radionuclides and types of monitoring data using
      real data contained in the IDEAS Internal Contamination Database. Based upon this
      work and other published values, default SF values are suggested. Uncertainty
      studies have been carried out using both a Bayesian approach as well as a
      frequentist (classical) approach. The IDEAS guidelines have been revised in areas
      relating to the evaluation of an effective AMAD, guidance is given on evaluating
      wound cases with the NCRP wound model and suggestions made on the number and type
      of measurements required for dose assessment.

PMID- 18718962
TI  - Analysis of a computational problem involving complex voxel geometries.
AB  - This communication briefly summarises the results obtained from the
      'International comparison on MC modeling for in vivo measurement of Americium in
      a knee phantom' organised within the EU Coordination Action CONRAD (Coordinated
      Network for Radiation Dosimetry) as a joint initiative of EURADOS working groups
      6 (computational dosimetry) and 7 (internal dosimetry). Monte Carlo simulations
      using the knee voxel phantom proved to be a viable approach to provide the
      calibration factor needed for in vivo measurements.

PMID- 18718963
TI  - A method for the determination of thoron and thoron progeny concentration at
      workplaces and thoron concentration in calibration chambers.
AB  - A new method to determine the air concentration of (220)Rn, commonly referred to
      as thoron, has been developed. The method is insensitive to the presence of any
      concentration of (222)Rn. Air turbulence, humidity and temperature do not
      influence the measurement. This method was primarily developed for field
      measurement of (220)Rn and (212)Pb concentrations at workplaces in underground
      environments with high ((222)Rn) concentration, but has the potential to be used
      for reference measurement of (220)Rn concentration in a calibration facility. The
      sampling and measurement devices are traceable to international standards. The
      proposed measuring technique has the potential to contribute to easy and accurate
      measurements of (220)Rn. This paper describes the method and an example of its
      use in underground workplaces.

PMID- 18718965
TI  - Intracellular phospholipase A(2) group IVA and group VIA play important roles in
      Wallerian degeneration and axon regeneration after peripheral nerve injury.
AB  - We provide evidence that two members of the intracellular phospholipase A(2)
      family, namely calcium-dependent group IVA (cPLA(2) GIVA) and calcium-independent
      group VIA (iPLA(2) GVIA) may play important roles in Wallerian degeneration in
      the mouse sciatic nerve. We assessed the roles of these PLA(2)s in cPLA(2) GIVA(
      /-) mice, and mice treated with a selective inhibitor of iPLA(2) GVIA (FKGK11).
      Additionally, the effects of both these PLA(2)s were assessed by treating cPLA(2)
      GIVA(-/-) mice with the iPLA(2) inhibitor. Our data suggest that iPLA(2) GVIA may
      play more of a role in the early stages of myelin breakdown, while cPLA(2) GIVA
      may play a greater role in myelin clearance by macrophages. Our results also show
      that the delayed myelin clearance and Wallerian degeneration after sciatic nerve
      crush injury in mice lacking cPLA(2) and iPLA(2) activities is accompanied by a
      delay in axon regeneration, target re-innervation and functional recovery. These
      results indicate that the intracellular PLA(2)s (cPLA(2) GIVA and iPLA(2) GVIA)
      contribute significantly to various aspects of Wallerian degeneration in injured
      peripheral nerves, which is then essential for successful axon regeneration. This
      work has implications for injury responses and recovery after peripheral nerve
      injuries in humans, as well as for understanding the slow clearance of myelin
      after CNS injury and its potential consequences for axon regeneration.

PMID- 18718966
TI  - Olfactory dysfunction in patients with narcolepsy with cataplexy is restored by
      intranasal Orexin A (Hypocretin-1).
AB  - Until recently, olfactory dysfunction was an unknown feature of narcolepsy.
      Orexin A, also called hypocretin-1, is abnormally decreased or undetectable in
      the cerebrospinal fluid of narcoleptic patients with cataplexies. As hypothalamic
      orexin-containing neurons project throughout the entire olfactory pathway, from
      the olfactory mucosa to the olfactory cortex, disturbed orexinergic transmission
      may crucially be involved in impaired olfactory performance of narcolepsy
      patients. In our study we analysed the olfactory performance (threshold,
      discrimination, identification and sum score of these measurements, the TDI
      score) of narcoleptic patients with cataplexies (n = 10) and of age-, gender-,
      BMI- and smoker/non-smoker-matched healthy controls (n = 10). We then in a double
      blind, randomized, placebo-controlled cross-over design applied orexin A
      intranasally to seven of the patients and measured 2-phenyl-ethyl alcohol (PEA)
      single-staircase odour detection thresholds. Compared to the controls, patients
      showed significantly lower scores for olfactory threshold (patients: median 8.0,
      range 4.0-10.5; controls: median 9.4, range 7.5-13.3; P < 0.05), discrimination
      (patients: median 12.5, range 10-15; controls: median 15.0, range 12-16; P <
      0.005), identification (patients: median 13.0, range 10-16; controls: median
      14.0, range 13-16; P < 0.05) and TDI score (patients: median 33.4, range 30-36;
      controls: median 38.4, range 35-43; P < 0.0001). In all patients, the PEA
      olfactory threshold score increased after administration of orexin A (median
      11.5, range 6.5-13.25) compared to placebo (median 7.75, range 6.25-11.25; P <
      0.05). Our results support the hypothesis that mild olfactory dysfunction is an
      intrinsic symptom of narcolepsy with cataplexies. The observation that intranasal
      orexin A restores olfactory function is in favour of this hypothesis.
      Furthermore, our data support that the pathophysiological mechanism underlying
      olfactory dysfunction in narcolepsy is the lack of CNS orexin.

PMID- 18718967
TI  - Benign childhood focal epilepsies: assessment of established and newly recognized
      syndromes.
AB  - A big advance in epileptology has been the recognition of syndromes with distinct
      aetiology, clinical and EEG features, treatment and prognosis. A prime and common
      example of this is rolandic epilepsy that is well known by the general
      paediatricians for over 50 years, thus allowing a precise diagnosis that predicts
      an excellent prognosis. However, rolandic is not the only benign childhood
      epileptic syndrome. Converging evidence from multiple and independent clinical,
      EEG and magnetoencephalographic studies has documented Panayiotopoulos syndrome
      (PS) as a model of childhood autonomic epilepsy, which is also common and benign.
      Despite high prevalence, lengthy and dramatic features, PS as well as autonomic
      status epilepticus had eluded recognition because emetic and other ictal
      autonomic manifestations were dismissed as non-epileptic events of other
      diseases. Furthermore, PS because of frequent EEG occipital spikes has been
      erroneously considered as occipital epilepsy and thus confused with the
      idiopathic childhood occipital epilepsy of Gastaut (ICOE-G), which is another age
      related but rarer and of unpredictable prognosis syndrome. Encephalitis is a
      common misdiagnosis for PS and migraine with visual aura for ICOE-G.
      Pathophysiologically, the symptomatogenic zone appears to correspond to the
      epileptogenic zone in rolandic epilepsy (sensory-motor symptomatology of the
      rolandic cortex) and the ICOE-G (occipital lobe symptomatology), while the
      autonomic clinical manifestations of PS are likely to be generated by variable
      and widely spread epileptogenic foci acting upon a temporarily hyperexcitable
      central autonomic network. Rolandic epilepsy, PS, ICOE-G and other possible
      clinical phenotypes of benign childhood focal seizures are likely to be linked
      together by a genetically determined, functional derangement of the systemic
      brain maturation that is age related (benign childhood seizure susceptibility
      syndrome). This is usually mild but exceptionally it may diverge to serious
      epileptic disorders such as epileptic encephalopathy with continuous spike and
      wave during sleep. Links with other benign and age-related seizures in early life
      such as febrile seizures, benign focal neonatal and infantile seizures is
      possible. Overlap with idiopathic generalized epilepsies is limited and of
      uncertain genetic significance. Taking all these into account, benign childhood
      focal seizures and related epileptic syndromes would need proper multi
      disciplinary re-assessment in an evidence-based manner.

PMID- 18718968
TI  - Exhaustion of caregivers of patients on maintenance haemodialysis.

PMID- 18718969
TI  - Survival with retinoblastoma in the USA: 1975-2004.
AB  - BACKGROUND: The purpose of this study was to determine the survival of
      retinoblastoma in the USA over a 30-year period from 1975 to 2004 using a
      systematic review of existing databases. METHODS: Nine hundred and ninety-two
      cases of retinoblastoma (International Classification of Oncology (ICDO-3) codes
      C69.2 (retina) and C69.9 (eye, NOS)) were derived from the Surveillance,
      Epidemiology and End Results (SEER) program database in the USA from 1975 to
      2004. All 17 current SEER registries were utilised to allow for optimal patient
      volume for statistical analysis. Survival rates were calculated by the Kaplan
      Meier method and differences evaluated with logrank and Wilcoxon tests. Cause of
      death was obtained and reviewed for all deceased patients. All retinoblastoma
      patient records were reviewed for treatments given and occurrence of second
      malignant neoplasms. RESULTS: There were a total of 990 distinct patients with
      retinoblastoma. Almost all cases (99.1%) were reported by the hospitals, and
      histopathological confirmation was available in 87.7% of cases. Over the period
      of 30 years (1975-2004), the 5-year observed actuarial survival rate increased
      from 92.3% (1975-84) to 93.9% (1985-94) to 96.5% (1995-2004). The difference in
      rates was statistically significant (Wilcoxon = 6.2393, p = 0.0442). The
      proportion of cases treated with radiotherapy first increased from 20.5% in 1975
      9 to 34.6% in 1985-9 and then sharply decreased to 6.5% in 2000-4. CONCLUSIONS:
      Over the last 30 years, there has been a gradual improvement in 5-year survival
      of children with retinoblastoma in the USA.

PMID- 18718970
TI  - Rings around cones.

PMID- 18718971
TI  - Experimental muscle pain during a forward lunge--the effects on knee joint
      dynamics and electromyographic activity.
AB  - OBJECTIVE: The purpose of this study was to investigate whether the knee joint
      dynamics during a forward lunge could be modulated by experimentally induced
      vastus medialis pain in healthy subjects. DESIGN: Randomised cross-over study.
      SETTING: Biomechanical movement laboratory. PARTICIPANTS: 20 healthy subjects
      were included. One subject was excluded during data collection. INTERVENTION: The
      subjects performed forward lunges before, during and 20 minutes after induction
      of experimental quadriceps muscle pain. Muscle pain was induced using hypertonic
      saline (5.8%) injected intramuscularly. Isotonic saline (0.9%) was used as
      control. MAIN OUTCOME MEASUREMENTS: Three-dimensional movement analyses were
      performed and inverse dynamics were used to calculate joint kinematics and
      kinetics for ankle, knee and hip joints. Electromyographic (EMG) signals of the
      hamstrings and quadriceps muscles were recorded. RESULTS: During and after pain,
      significant decreases in knee joint dynamics and EMG recordings were observed.
      CONCLUSION: The study shows that local pain in the quadriceps is capable of
      modulating movements with high knee joint dynamics. The results may have
      implications in the management of muscle pain and prevention of injuries during
      activities involving the knee joint.

PMID- 18718972
TI  - Antibiotic treatment in patients with low-back pain associated with Modic changes
      Type 1 (bone oedema): a pilot study.
AB  - OBJECTIVE: The aim of this study was to assess the clinical effect of antibiotic
      treatment in a cohort of patients with low-back pain (LBP) and Modic changes Type
      1 (bone oedema) following a lumbar herniated disc. DESIGN: This was a prospective
      uncontrolled trial of 32 LBP patients who had Modic changes and were treated with
      Amoxicillin-clavulanate (500 mg/125 mg) 3 x day for 90 days. All patients had
      previously participated in a randomised controlled trial (RCT) that investigated
      active conservative treatment for a lumbar herniated disc (n = 166). All patients
      in that RCT who had Modic changes and LBP at 14 months follow-up (n = 37) were
      invited to participate in this subsequent antibiotic trial but five did not meet
      the inclusion criteria. RESULTS: 29 patients completed the treatment, as three
      patients dropped out due to severe diarrhoea. At the end of treatment and at long
      term follow-up (mean 10.8 months) there was both clinically important and
      statistically significant (p<or=0.001) improvement in all outcome measures: LBP
      intensity, number of days with pain, disease-specific and patient-specific
      function, and global perceived effect. CONCLUSIONS: In this uncontrolled trial,
      the clinical effect of antibiotic treatment was large in a group of patients with
      Modic changes suffering from persistent LBP following a disc herniation. These
      results provide tentative support for a hypothesis that bacterial infection may
      play a role in LBP with Modic changes and indicate the need for randomised
      controlled trials to test this hypothesis.

PMID- 18718973
TI  - Is the measurement of maximal oxygen intake passe?

PMID- 18718974
TI  - Sudden cardiac arrest in children and young athletes: the importance of a
      detailed personal and family history in the pre-participation evaluation.
AB  - Healthcare providers have become more aware of and concerned about paediatric
      sudden cardiac arrest. The diseases predisposing a patient to sudden cardiac
      arrest are all infrequently encountered. However, a detailed and comprehensive
      patient and family history may reveal warning signs and symptoms that identify a
      patient at higher risk for sudden cardiac arrest. Since many of these diseases
      are genetic, extensive family evaluation may uncover a previously undetected
      cardiac disease process and as well direct the development of a complete family
      evaluation and treatment plan. Published data document that in many cases
      preceding warning symptoms and signs are present, but may be misinterpreted or
      disregarded by medical staff. Attention to the details of patient history, family
      history and physical exam is critical to the success of any detection strategy,
      which can and should be widely applied.

PMID- 18718975
TI  - Extracorporeal shockwave therapy for patellar tendinopathy: a review of the
      literature.
AB  - BACKGROUND AND PURPOSE: Extracorporeal shockwave therapy (EWST) has become a
      popular treatment for patellar tendinopathy. The purpose of this review was to
      study the effectiveness of ESWT treatment for patellar tendinopathy; to draft
      guidelines for an effective treatment protocol of ESWT treatment; and to identify
      topics for further research. METHODS: A computerised search of the Medline and
      Embase databases was conducted on 1 August 2007, to identify studies dealing with
      the effectiveness of ESWT for patellar tendinopathy. RESULTS: Seven articles
      describing the effectiveness of ESWT on patellar tendinopathy, all published
      after 2000, were included. These studies included a total of 283 patients (298
      tendons), 204 of whom (215 tendons) were assigned to ESWT treatment. The
      treatment results were positive but most studies had methodological deficiencies,
      small numbers and/or short follow-up periods. Method of application and shockwave
      generation, energy level, number and frequency of treatments, use of (local)
      anaesthesia and method of localisation were variable. CONCLUSION: ESWT seems to
      be a safe and promising treatment for patellar tendinopathy with a positive
      effect on pain and function. Based on current knowledge it is impossible to
      recommend a specific treatment protocol. Further basic and clinical research into
      the working mechanism and effectiveness of ESWT for patellar tendinopathy are
      necessary.

PMID- 18718976
TI  - The ACTN3 R577X polymorphism in Russian endurance athletes.
AB  - OBJECTIVE: The functional 577R allele of the alpha-actinin-3 (ACTN3) gene has
      been reported to be associated with elite power athlete status, while the
      nonfunctional 577XX genotype (predicts an alpha-actinin-3 deficient phenotype)
      has been hypothesised as providing some sort of advantage for endurance athletes.
      In the present study, the distribution of ACTN3 genotypes and alleles in Russian
      endurance-oriented athletes were examined and association between ACTN3 genotypes
      and the competition results of rowers were sought. METHODS: 456 Russian endurance
      oriented athletes of regional or national competitive standard were involved in
      the study. ACTN3 genotype and allele frequencies were compared with 1211
      controls. The data from the Russian Cup Rowing Tournament were used to search for
      possible association between the ACTN3 genotype and the long-distance
      (approximately 6 km) rowing results of 54 athletes. DNA was extracted from
      mouthwash samples. Genotyping for the R577X variant was performed by PCR and
      restriction enzyme digestion. RESULTS: The frequencies of the ACTN3 577XX
      genotype (5.7% vs 14.5%; p<0.0001) and 577X allele (33.2% vs 39.0%; p = 0.0025)
      were significantly lower in endurance-oriented athletes compared with the
      controls, and none of the highly elite athletes had the 577XX genotype.
      Furthermore, male rowers with ACTN3 577RR genotype showed better results (1339
      (11) s) in long-distance rowing than carriers of 577RX (1386 (12) s) or 577XX
      (1402 (10) s) genotypes (p = 0.016). CONCLUSION: Our data show that the ACTN3
      577X allele is under-represented in Russian endurance athletes and is associated
      with the rowers' competition results.

PMID- 18718977
TI  - How do I measure physical activity in my patients? Questionnaires and objective
      methods.
AB  - How do healthcare providers know if their patients are getting enough physical
      activity to promote good health and to reduce their risks of chronic diseases and
      injury? The first step is to identify the patient's current level of physical
      activity using questionnaires and/or motion sensors. Questionnaires assess
      activity levels by having patients answer a set of questions about the types and
      amounts of activity performed at some time in the past. Motion sensors assess
      physical activity by patients wearing a small monitoring device that records
      their body movement as it occurs. If a provider is interested in determining a
      patient's caloric energy expenditure, he/she can apply statistical regression
      models to the questionnaire and motion sensor data to estimate kilocalories. If
      more precise measures of energy expenditure are desired, a provider can use the
      isotopic doubly labelled water method to estimate kilocalories; however, this
      method is costly and is impractical in non-research clinical settings.

PMID- 18718978
TI  - A 12-month prospective cohort study of injury in international rowers.
AB  - OBJECTIVE: In this study, the injury incidence and association with type and
      volume of training in international rowers were described. DESIGN: A prospective
      cohort design was used over a 12-month period. PATIENTS: 20 international rowers
      who were competing as part of the Irish Amateur Rowing Union squad system.
      METHODS: The rowers were interviewed monthly, and data were collected regarding
      their training and competition exposure as well as their injury experience.
      RESULTS: A mean injury rate of 3.67 per 1000 exposure hours was reported with a
      total of 44 injuries reported in a 12-month period. The mean number of injuries
      sustained per athlete was 2.2 (1.24) over the 12-month period. The area where the
      greatest number of injuries were reported was the lumbar spine (31.82% of total
      injuries, 95% CI 20 to 50) (fig 2) followed by the knee (15.91% of total
      injuries, 95% CI 10 to 30) and the cervical spine (11.36% of total injuries, 95%
      CI 5 to 24). Half of the injuries (22 injuries, 50% of total reported injuries)
      were to the spine (chi(2) = 30.8, df = 9, p = 0.0003). Ergometer training load
      was the most significantly associated with injury risk (r = 0.68, p = 0.01).
      CONCLUSION: International rowers are at higher risk of injury than most non
      contact sports and some contact sports. The high risk of lumbar spine injury and
      the significant association of high volume of ergometer training merit further
      research to reduce time and competition lost to injury.

PMID- 18718979
TI  - Paths to literacy and numeracy problems: evidence from two British birth cohorts.
AB  - BACKGROUND: To test a life course model linking circumstances of origin to self
      reported literacy and numeracy problems in midlife, and to investigate the
      effects in this model of changing social circumstances in two post-war cohorts.
      METHODS: Based on data from men and women in the British 1946 and 1958 birth
      cohorts, we used the relative index of inequality and logistical regression to
      test associations between father's occupation, childhood cognition, educational
      attainment, own occupation in the third decade, and a binary variable
      representing self-reported literacy and numeracy problems in the fourth decade.
      RESULTS: There was a lower frequency of literacy and numeracy problems in the
      1958 cohort than in the 1946 cohort. In both cohorts there were associations
      between father's occupation and childhood cognition, educational attainment and
      own occupation, a pattern that was mirrored by the associations between childhood
      cognition, educational attainment and own occupation to adult literacy and
      numeracy problems. Positive associations between childhood cognition and
      educational attainment, and between educational attainment and own occupation,
      were stronger in the 1946 cohort than in the 1958 cohort. However, inverse
      associations between educational attainment and literacy and numeracy problems
      were stronger in the 1958 cohort, possibly reflecting the expansion of secondary
      education in the intervening years. CONCLUSIONS: Literacy and numeracy problems
      have a robust structure of life course associations, although the changing
      pattern of these associations may reflect important social structural changes
      from the early post-war years to the early 1960s in the UK.

PMID- 18718980
TI  - Maternal glucose tolerance status influences the risk of macrosomia in male but
      not in female fetuses.
AB  - OBJECTIVE: To elucidate whether the risk of macrosomia, large for gestational age
      (LGA) and small for gestational age (SGA) is influenced by maternal body mass
      index and glucose tolerance differently in male and female fetuses. METHODS: A
      population study was conducted in 16 general hospitals from the Spanish National
      Health Service that included 9270 consecutive women with singleton pregnancies
      and without a former diagnosis of diabetes mellitus who delivered 4793 male and
      4477 female newborns. Logistic regression analyses were performed to predict the
      effect of body mass index (BMI) category and glucose tolerance on macrosomia,
      large for gestational age newborns (LGA) and small for gestational age newborns
      (SGA) Separate analyses according to foetal sex were carried out for each
      outcome. The results were adjusted for maternal age, gestational age and
      pregnancy-induced hypertension. RESULTS: There were significant differences
      between males and females in the percentage of infants who had macrosomia, LGA or
      SGA. Maternal BMI category was positively associated with the risk of macrosomia
      and LGA in both male and female newborns. In addition, there was a negative
      association between maternal BMI and SGA that only reached significance in males.
      In contrast, gestational diabetes was only a predictor of macrosomia exclusively
      in male fetuses (OR 1.67, 95% CI 1.12 to 2.49) CONCLUSIONS: There is sexual
      dimorphism in the risk of abnormal birth weight attributed to maternal glucose
      tolerance status. A closer surveillance of foetal growth might be warranted in
      pregnant women with abnormal glucose tolerance carrying a male fetus.

PMID- 18718981
TI  - Reviewing evidence on complex social interventions: appraising implementation in
      systematic reviews of the health effects of organisational-level workplace
      interventions.
AB  - BACKGROUND: The reporting of intervention implementation in studies included in
      systematic reviews of organisational-level workplace interventions was appraised.
      Implementation is taken to include such factors as intervention setting,
      resources, planning, collaborations, delivery and macro-level socioeconomic
      contexts. Understanding how implementation affects intervention outcomes may help
      prevent erroneous conclusions and misleading assumptions about generalisability,
      but implementation must be adequately reported if it is to be taken into account.
      METHODS: Data on implementation were obtained from four systematic reviews of
      complex interventions in workplace settings. Implementation was appraised using a
      specially developed checklist and by means of an unstructured reading of the
      text. RESULTS: 103 studies were identified and appraised, evaluating four types
      of organisational-level workplace intervention (employee participation, changing
      job tasks, shift changes and compressed working weeks). Many studies referred to
      implementation, but reporting was generally poor and anecdotal in form. This poor
      quality of reporting did not vary greatly by type or date of publication. A
      minority of studies described how implementation may have influenced outcomes.
      These descriptions were more usefully explored through an unstructured reading of
      the text, rather than by means of the checklist. CONCLUSIONS: Evaluations of
      complex interventions should include more detailed reporting of implementation
      and consider how to measure quality of implementation. The checklist helped us
      explore the poor reporting of implementation in a more systematic fashion. In
      terms of interpreting study findings and their transferability, however, the more
      qualitative appraisals appeared to offer greater potential for exploring how
      implementation may influence the findings of specific evaluations. Implementation
      appraisal techniques for systematic reviews of complex interventions require
      further development and testing.

PMID- 18718982
TI  - Association of haplotypes spanning PDZ-GEF2, LOC728637 and ACSL6 with
      schizophrenia in Han Chinese.
AB  - BACKGROUND: Schizophrenia is a complex genetic disorder caused by multiple
      genetic and environmental factors. Several lines of linkage and association
      studies have repeatedly suggested that the chromosome 5q22-33 region is
      implicated in the aetiology of schizophrenia. However, most of the previous
      studies on the linkage of 5q22-33 with schizophrenia were from European
      populations, and it was not well characterised in other populations. METHODS: We
      analysed eight single nucleotide polymorphisms (SNPs) located in the 5q23.3
      region in a cohort of 506 schizophrenia patients and 672 control subjects from
      south western China. Single marker association, haplotypic association, sex
      specific association and molecular evolutionary analysis were performed. RESULTS:
      Single marker analysis indicated that SNP5 (rs1355095) in LOC728637 is associated
      with schizophrenia. When males and females were analysed separately, SNP4
      (rs31251) in PDZ-GEF2 is associated with schizophrenia in females. Further
      analysis using haplotypes demonstrated that a haplotype block spanning PDZ-GEF2,
      LOC728637 and ACSL6 is highly associated with schizophrenia and several
      haplotypes in this haploblock have about twofold to 10-fold increase in the
      affected subjects. In addition, molecular evolutionary analysis suggests that PDZ
      GEF2 has undergone adaptive evolution due to Darwinian positive selection in the
      human lineage. CONCLUSION: Our data provide evidence of the association of 5q22
      33 with schizophrenia in Han Chinese. This chromosomal region is likely
      responsible for genetic susceptibility to schizophrenia, supporting previous data
      from European patients. In addition, our evolutionary analysis is consistent with
      the hypothesis that genes contributing to schizophrenia are likely under positive
      selection during human evolution.

PMID- 18718983
TI  - Mobility of NMDA autoreceptors but not postsynaptic receptors at glutamate
      synapses in the rat entorhinal cortex.
AB  - NMDA receptors (NMDAr) are known to undergo recycling and lateral diffusion in
      postsynaptic spines and dendrites. However, NMDAr are also present as
      autoreceptors on glutamate terminals, where they act to facilitate glutamate
      release, but it is not known whether these receptors are also mobile. We have
      used functional pharmacological approaches to examine whether NMDA receptors at
      excitatory synapses in the rat entorhinal cortex are mobile at either
      postsynaptic sites or in presynaptic terminals. When NMDAr-mediated evoked EPSCs
      (eEPSCs) were blocked by MK-801, they showed no evidence of recovery when the
      irreversible blocker was removed, suggesting that postsynaptic NMDAr were
      relatively stably anchored at these synapses. However, using frequency-dependent
      facilitation of AMPA receptor (AMPAr)-mediated eEPSCs as a reporter of
      presynaptic NMDAr activity, we found that when facilitation was blocked with MK
      801 there was a rapid (approximately 30-40 min) anomalous recovery upon removal
      of the antagonist. This was not observed when global NMDAr blockade was induced
      by combined perfusion with MK-801 and NMDA. Anomalous recovery was accompanied by
      an increase in frequency of spontaneous EPSCs, and a variable increase in
      frequency-facilitation. Following recovery from blockade of presynaptic NMDAr
      with a competitive antagonist, frequency-dependent facilitation of AMPAr-mediated
      eEPSCs was also transiently enhanced. Finally, an increase in frequency of
      miniature EPSCs induced by NMDA was succeeded by a persistent decrease. Our data
      provide the first evidence for mobility of NMDAr in the presynaptic terminals,
      and may point to a role of this process in activity-dependent control of
      glutamate release.

PMID- 18718984
TI  - Maternal dietary supplementation with saturated, but not monounsaturated or
      polyunsaturated fatty acids, leads to tissue-specific inhibition of offspring
      Na+,K+-ATPase.
AB  - In rats, a maternal diet rich in lard is associated with reduced Na(+),K(+)
      ATPase activity in adult offspring kidney. We have addressed the role of
      different fatty acids by evaluating Na(+),K(+)-ATPase activity in offspring of
      dams fed diets rich in saturated (SFA), monounsaturated (MUFA) or polyunsaturated
      (PUFA) fatty acids. Female Sprague-Dawley rats were fed, during pregnancy and
      suckling, a control diet (4% w/w corn oil) or a fatty acid supplemented diet (24%
      w/w). Offspring were reared on chow (4% PUFA) and studied at 6 months. mRNA
      expression (real-time PCR) of Na(+),K(+)-ATPase alpha subunit and protein
      expression of Na(+),K(+)-ATPase subunits (Western blot) were assessed in kidney
      and brain. Na(+),K(+)-ATPase activity was reduced in kidney (P < 0.05 versus all
      groups) and brain (P < 0.05 versus control and MUFA offspring) of the SFA group.
      Neither Na(+),K(+)-ATPase alpha1 subunit mRNA expression, nor protein expression
      of total alpha, alpha1, alpha2, alpha3 or beta1 subunits were significantly
      altered in kidney in any dietary group. In brains of SFA offspring alpha1 mRNA
      expression (P < 0.05) was reduced compared with MUFA and PUFA offspring, but not
      controls. Also in brain, SFA offspring demonstrated reduced (P < 0.05) alpha1
      subunit protein and increased phosphorylation (P < 0.05) of the Na(+),K(+)-ATPase
      modulating protein phospholemman at serine residue 63 (S63 PLM). Na(+),K(+)
      ATPase activity was similar to controls in heart and liver. In utero and neonatal
      exposure to a maternal diet rich in saturated fatty acids is associated with
      altered activity and expression of Na(+),K(+)-ATPase in adulthood, but mechanisms
      appear tissue specific.

PMID- 18718985
TI  - ERG voltage-gated K+ channels regulate excitability and discharge dynamics of the
      medial vestibular nucleus neurones.
AB  - The discharge properties of the medial vestibular nucleus neurones (MVNn)
      critically depend on the activity of several ion channel types. In this study we
      show, immunohistochemically, that the voltage-gated K(+) channels ERG1A, ERG1B,
      ERG2 and ERG3 are highly expressed within the vestibular nuclei of P10 and P60
      mice. The role played by these channels in the spike-generating mechanisms of the
      MVNn and in temporal information processing was investigated
      electrophysiologically from mouse brain slices, in vitro, by analysing the
      spontaneous discharge and the response to square-, ramp- and sinusoid-like
      intracellular DC current injections in extracellular and whole-cell patch-clamp
      studies. We show that more than half of the recorded MVNn were responsive to ERG
      channel block (WAY-123,398, E4031), displaying an increase in spontaneous
      activity and discharge irregularity. The response to step and ramp current
      injection was also modified by ERG block showing a reduction of first spike
      latency, enhancement of discharge rate and reduction of the slow spike-frequency
      adaptation process. ERG channels influence the interspike slope without affecting
      the spike shape. Moreover, in response to sinusoid-like current, ERG channel
      block caused frequency-dependent gain enhancement and phase-lead shift. Taken
      together, the data demonstrate that ERG channels control the excitability of
      MVNn, their discharge regularity and probably their resonance properties.

PMID- 18718987
TI  - Does low-field dedicated extremity MRI (E-MRI) reliably detect bone erosions in
      rheumatoid arthritis? A comparison of two different E-MRI units and conventional
      radiography with high-resolution CT scanning.
AB  - OBJECTIVES: To compare the ability of two different E-MRI units and conventional
      radiography (CR) to identify bone erosions in rheumatoid arthritis (RA)
      metacarpophalangeal (MCP) and wrist joints with CT scanning as the standard
      reference method. METHODS: 20 patients with RA and 5 controls underwent CR, CT
      and two E-MRI examinations (Esaote Biomedica Artoscan and MagneVu MV1000) of one
      hand during a 2-week period. In all modalities, each bone of the wrist and MCP
      joints was blindly evaluated for erosions. MagneVu images were also assessed for
      the proportion of each bone being visualised. RESULTS: 550 bones were examined.
      CT, Artoscan, MagneVu and CR detected 188, 116, 55 and 45 bones with erosions,
      respectively. The majority were located in the carpal bones. The sensitivity of
      the Artoscan for detecting erosions was higher than that of the MagneVu and CR
      (MCP joints: 0.68, 0.54 and 0.57, respectively; wrists: 0.50, 0.23 and 0.29).
      Corresponding specificities for detecting erosions were 0.94, 0.93 and 0.99,
      respectively, in the MCP joints and 0.92, 0.98 and 0.98 in the wrist. The MagneVu
      allowed visualisation of 1.5 cm of the ventral-dorsal diameter of the bone. In
      the wrist, 31.6% of bones were visualised entirely and 37.9% of bones were 67-99%
      visualised. In MCP joints, 84.2% of bones were visualised entirely and 15.8% of
      bones were 67-99% visualised. CONCLUSION: With CT as the reference method for
      detecting erosions in RA hands, the Artoscan showed higher sensitivity than the
      MagneVu and CR. All imaging modalities had high specificities. The better
      performance of the Artoscan should be considered when selecting an imaging method
      in RA.

PMID- 18718986
TI  - Inhibition of radiographic progression with combination etanercept and
      methotrexate in patients with moderately active rheumatoid arthritis previously
      treated with monotherapy.
AB  - OBJECTIVE: To determine the effect of changing from etanercept or methotrexate
      monotherapy to etanercept plus methotrexate combination therapy on radiographic
      progression in rheumatoid arthritis (RA) patients. METHODS: Patients enrolled in
      this 1-year open-label study previously completed a 3-year blinded study in which
      they received methotrexate or etanercept monotherapy or the combination of both.
      All patients received the combination of etanercept 25 mg subcutaneously twice
      weekly plus oral methotrexate up to 20 mg/week. The primary radiographic endpoint
      was a change in modified total Sharp score (TSS), as assessed by blinded readers.
      RESULTS: At baseline, patients previously receiving methotrexate monotherapy
      (etanercept-added, n = 52) or etanercept monotherapy (methotrexate-added, n = 68)
      had moderate disease activity levels (mean disease activity score (DAS) of 2.6
      and 2.5, respectively), whereas patients previously receiving combination therapy
      (n = 90) had a low disease activity level (mean DAS of 2.0). The addition of
      etanercept to methotrexate monotherapy resulted in a significant reduction in
      radiographic progression (p<0.05). Mean TSS changes in the previous year versus
      the current year were +1.79 versus +0.25 for the etanercept-added group (p<0.05);
      +0.51 versus -0.18 for the methotrexate-added group (NS) and +0.42 versus +0.24
      for the combination group (NS). CONCLUSION: In these RA patients with on average
      moderate disease activity despite previous methotrexate monotherapy, combination
      treatment with etanercept and methotrexate inhibited radiographic progression and
      improved radiographic outcomes. These data, in conjunction with the previously
      published clinical data, support the use of combination therapy in RA patients
      with moderate disease activity.

PMID- 18718988
TI  - Prevalence of radiographic lumbar spondylosis and its association with low back
      pain in elderly subjects of population-based cohorts: the ROAD study.
AB  - OBJECTIVES: Although lumbar spondylosis is a major cause of low back pain and
      disability in elderly people, few epidemiological studies have been performed.
      The prevalence of radiographic lumbar spondylosis was investigated in a large
      scale population study and the association with low back pain was examined.
      METHODS: From a nationwide cohort study (Research on Osteoarthritis Against
      Disability; ROAD), 2288 participants aged > or =60 years (818 men and 1470 women)
      living in urban, mountainous and coastal communities were analysed. The
      radiographic severity at lumbar intervertebral levels from L1/2 to L5/S was
      determined by Kellgren/Lawrence (KL) grading. RESULTS: In the overall population
      the prevalence of radiographic spondylosis with KL> or =2 and > or =3 at the
      severest intervertebral level was 75.8% and 50.4%, respectively, and that of low
      back pain was 28.8%. Although KL> or =2 spondylosis was more prevalent in men,
      KL> or =3 spondylosis and low back pain were more prevalent in women. Age and
      body mass index were risk factors for both KL > or =2 and KL> or =3 spondylosis.
      Although KL = 2 spondylosis was not significantly associated with low back pain
      compared with KL = 0 or 1, KL> or =3 spondylosis was related to the pain only in
      women. CONCLUSIONS: This cross-sectional study in a large population revealed a
      high prevalence of radiographic lumbar spondylosis in elderly subjects. Gender
      seems to be distinctly associated with KL> or =2 and KL> or =3 lumbar
      spondylosis, and disc space narrowing with or without osteophytosis in women may
      be a risk factor for low back pain.

PMID- 18718989
TI  - Are laboratory tests useful for monitoring the activity of lupus nephritis? A 6
      year prospective study in a cohort of 228 patients with lupus nephritis.
AB  - OBJECTIVES: To evaluate the role of immunological tests for monitoring lupus
      nephritis (LN) activity. METHODS: C3, C4, anti-dsDNA and anti-C1q antibodies were
      prospectively performed over 6 years in 228 patients with LN. RESULTS: In
      membranous LN only anti-C1q antibodies differentiated proteinuric flares from
      quiescent disease (p = 0.02). However, in this group 46% of flares occurred with
      a normal value of anti-C1q antibodies versus 20% in proliferative LN (p = 0.02).
      In patients with antiphospholipid antibodies (APL), 33% of flares occurred with
      normal levels of anti-C1q antibodies versus 14.5% in patients that were APL
      negative (p = 0.02). In proliferative LN, anti-C1q antibodies showed a slightly
      better sensitivity and specificity (80.5 and 71% respectively) than other tests
      for the diagnosis of renal flares. All four tests had good negative predictive
      value (NPV). At univariate analysis anti-C1q was the best renal flare predictor
      (p<0.0005). At multivariate analysis, the association of anti-C1q with C3 and C4
      provided the best performance (p<0.0005, p<0.005, p<0.005 respectively).
      CONCLUSIONS: Anti-C1q is slightly better than the other tests to confirm the
      clinical activity of LN, particularly in patients with proliferative LN and in
      the absence of APL. All four "specific" tests had a good NPV, suggesting that, in
      the presence of normal values of each, active LN is unlikely.

PMID- 18718991
TI  - A report on location of death in paediatric palliative care between home, hospice
      and hospital.
AB  - This retrospective study analysed data for 703 children who died from 2000 to
      2006 to examine where children with a broad range of progressive, life-limiting
      illnesses actually die when families are able to access hospital, paediatric
      hospice facility and care at home. There was an overall even distribution for
      location of death in which 35.1% of children died at home, 32.1% died in a
      paediatric hospice facility, 31.9% in hospital and 0.9% at another location.
      Previous research suggests a preference for home as the location of death, but
      these studies have primarily focused on adults, children with cancer or settings
      without paediatric hospice facilities available as an option. Our results suggest
      that the choice of families for end-of-life care is equally divided amongst all
      three options. Given the increasing numbers of children's hospices worldwide,
      these findings are important for clinicians, care managers and researchers who
      plan, provide and evaluate the care of children with life-limiting illness.

PMID- 18718990
TI  - The misuse/abuse of antihistamine antiemetic medication (cyclizine) by cancer
      patients.
AB  - Cyclizine is an antihistamine, which is frequently used to manage nausea and
      vomiting in cancer patients. Antihistamines can be drugs of misuse/abuse, and the
      article describes four cancer patients who developed such problems after
      receiving parenteral cyclizine within the inpatient unit of a cancer centre. The
      article also briefly reviews the literature on the misuse/abuse of cyclizine and
      other antihistamines.

PMID- 18718992
TI  - Letter to editor: an observational study of red cell transfusion in specialist
      palliative care.

PMID- 18718993
TI  - Role of advance directives in palliative care units: a prospective study.
AB  - Advance directives (ADs) might be useful in achieving improved communication and
      satisfaction with decision making at the end-of-life. Our aims were to better
      characterise patients with advanced oncological disease who decided to complete
      ADs and to measure the effect of ADs completion on the satisfaction level with
      end-of-life care from both patients and their relatives. A prospective study was
      conducted in three palliative care units. Patients with advanced cancer were
      included if they met the following criteria: an estimated life expectancy of <6
      months, fluency in French, Mini Mental State Examination >20 and not yet
      completed ADs. All the patients received information about ADs and decided
      whether to complete ADs or not. The level of satisfaction with involvement in the
      decision process concerning end-of-life care was assessed by means of a written
      questionnaire. In all, 53 of 228 patients were included, and 12 decided to
      complete ADs. Patients who completed ADs had statistically less depression one
      week after inclusion (P = 0.030), had a lower anxiety score on the second week
      and had a lower depression score on the third week. There was a trend towards a
      higher satisfaction level with the involvement of the patients in end-of-life
      care for those completing ADs (P = 0.878). In conclusion, each patient with an
      advanced progressive disease should be informed about ADs and be encouraged to
      complete the ADs with the aim to ease many fears as well as to improve
      communication.

PMID- 18718995
TI  - CMA adopts new governance structure.

PMID- 18718996
TI  - Lipopolysaccharide activates NF-kappaB by TLR4-Bcl10-dependent and independent
      pathways in colonic epithelial cells.
AB  - In colonic epithelium, one of the pathways of lipopolysaccharide (LPS) activation
      of NF-kappaB and IL-8 is via Toll-like receptor (TLR)4, MyD88, IRAK1/4, and B
      cell CLL/lymphoma 10 (Bcl10). However, this innate immune pathway accounts for
      only approximately 50% of the NF-kappaB activation, so additional mechanisms to
      explain the LPS-induced effects are required. In this report, we identify a
      second pathway of LPS-induced stimulation, mediated by reactive oxygen species
      (ROS), in human colonic epithelial tissue cells in tissue culture and in ex vivo
      mouse colonic tissue. Measurements of IL-8, KC, Bcl10, phospho-IkappaBalpha,
      nuclear NF-kappaB, and phosphorylated Hsp27 were performed by ELISA. The TLR4
      Bcl10 pathway was inhibited by Bcl10 siRNA and in studies with colonic tissue
      from the TLR4-deficient mouse. The ROS pathway was inhibited by Tempol, a free
      radical scavenger, or by okadaic acid, an inhibitor of Hsp27 dephosphorylation by
      protein phosphatase 2A (PP2A). The ROS pathway was unaffected in the TLR4
      deficient tissue or by silencing of Bcl10. The combination of exposure to the
      free radical scavenger Tempol and of TLR4 or Bcl10 suppression was required to
      completely inhibit the LPS-induced activation. The ROS pathway was associated
      with dephosphorylation of Hsp27. LPS appears to activate both the regulatory
      component of the IkappaBalpha-kinase (IKK) signalosome through Bcl10 interaction
      with Nemo (IKKgamma) and the catalytic component through Hsp27 interaction with
      IKKbeta. Since LPS exposure is associated with septic shock and the systemic
      inflammatory response syndrome, distinguishing between these two pathways of LPS
      activation may facilitate new approaches to prevention and treatment.

PMID- 18718997
TI  - Inhibiting intestinal NPC1L1 activity prevents diet-induced increase in biliary
      cholesterol in Golden Syrian hamsters.
AB  - Niemann-Pick C1-like 1 (NPC1L1) facilitates the uptake of sterols into the
      enterocyte and is the target of the novel cholesterol absorption inhibitor,
      ezetimibe. These studies used the Golden Syrian hamster as a model to delineate
      the changes in the relative mRNA expression of NPC1L1 and other proteins that
      regulate sterol homeostasis in the enterocyte during and following cessation of
      ezetimibe treatment and also to address the clinically important question of
      whether the marked inhibition of cholesterol absorption alters biliary lipid
      composition. In hamsters fed a low-cholesterol, low-fat basal diet, the abundance
      of mRNA for NPC1L1 in the small intestine far exceeded that in other regions of
      the gastrointestinal tract, liver, and gallbladder. In the first study, female
      hamsters were fed the basal diet containing ezetimibe at doses up to 2.0 mg.day(
      1).kg body wt(-1). At this dose, cholesterol absorption fell by 82%, fecal
      neutral sterol excretion increased by 5.3-fold, and hepatic and intestinal
      cholesterol synthesis increased more than twofold, but there were no significant
      changes in either fecal bile acid excretion or biliary lipid composition. The
      ezetimibe-induced changes in intestinal cholesterol handling were reversed when
      treatment was withdrawn. In a second study, male hamsters were given a diet
      enriched in cholesterol and safflower oil without or with ezetimibe. The lipid
      rich diet raised the absolute and relative cholesterol levels in bile more than
      fourfold. This increase was largely prevented by ezetimibe. These data are
      consistent with the recent finding that ezetimibe treatment significantly reduced
      biliary cholesterol saturation in patients with gallstones.

PMID- 18718998
TI  - Liquid in the gastroesophageal segment promotes reflux, but compliance does not:
      a mathematical modeling study.
AB  - The mechanical force relationships that distinguish normal from chronic reflux at
      sphincter opening are poorly understood and difficult to measure in vivo. Our aim
      was to apply physics-based computer simulations to determine mechanical
      pathogenesis of gastroesophageal reflux. A mathematical model of the
      gastroesophageal segment (GES) was developed, incorporating the primary
      anatomical and physiomechanical elements that drive GES opening and reflux. In
      vivo data were used to quantify muscle stiffness, sphincter tone, and gastric
      pressure. The liquid lining the mucosa was modeled as an "effective liquid film"
      between the mucosa and a manometric catheter. Newton's second law was solved
      mathematically, and the space-time details of opening and reflux were predicted
      for systematic variations in gastric pressure increase, film thickness, muscle
      stiffness, and tone. "Reflux" was defined as "2 ml of refluxate entering the
      esophagus within 1 s." GES opening and reflux were different events. Both were
      sensitive to changes in gastric pressure and sphincter tone. Reflux initiation
      was extremely sensitive to the liquid film thickness; the protective function of
      the sphincter was destroyed with only 0.4 mm of liquid in the GES. Compliance had
      no effect on reflux initiation, but affected reflux volume. The presence of
      abnormal levels of liquid within the collapsed GES can greatly increase the
      probability for reflux, suggesting a mechanical mechanism that may differentiate
      normal reflux from gastroesophageal reflux disease. Compliance does not affect
      the probability for reflux, but affects reflux volume once it occurs. Opening
      without reflux suggests the existence of "gastroesophageal pooling" in the distal
      esophagus, with clinical implications.

PMID- 18718999
TI  - Reduced absorption of saturated fatty acids and resistance to diet-induced
      obesity and diabetes by ezetimibe-treated and Npc1l1-/- mice.
AB  - The impact of NPC1L1 and ezetimibe on cholesterol absorption are well documented.
      However, their potential consequences relative to absorption and metabolism of
      other nutrients have been only minimally investigated. Thus studies were
      undertaken to investigate the possible effects of this protein and drug on fat
      absorption, weight gain, and glucose metabolism by using Npc1l1(-/-) and
      ezetimibe-treated mice fed control and high-fat, high-sucrose diets. Results show
      that lack of NPC1L1 or treatment with ezetimibe reduces weight gain when animals
      are fed a diabetogenic diet. This resistance to diet-induced obesity results, at
      least in part, from significantly reduced absorption of dietary saturated fatty
      acids, particularly stearate and palmitate, since food intake did not differ
      between groups. Expression analysis showed less fatty acid transport protein 4
      (FATP4) in intestinal scrapings of Npc1l1(-/-) and ezetimibe-treated mice,
      suggesting an important role for FATP4 in intestinal absorption of long-chain
      fatty acids. Concomitant with resistance to weight gain, lack of NPC1L1 or
      treatment with ezetimibe also conferred protection against diet-induced
      hyperglycemia and insulin resistance. These unexpected beneficial results may be
      clinically important, given the focus on NPC1L1 as a target for the treatment of
      hypercholesterolemia.

PMID- 18719000
TI  - The gastric mucus layers: constituents and regulation of accumulation.
AB  - The mucus layer continuously covering the gastric mucosa consists of a loosely
      adherent layer that can be easily removed by suction, leaving a firmly adherent
      mucus layer attached to the epithelium. These two layers exhibit different
      gastroprotective roles; therefore, individual regulation of thickness and mucin
      composition were studied. Mucus thickness was measured in vivo with micropipettes
      in anesthetized mice [isoflurane; C57BL/6, Muc1-/-, inducible nitric oxide
      synthase (iNOS)-/-, and neuronal NOS (nNOS)-/-] and rats (inactin) after surgical
      exposure of the gastric mucosa. The two mucus layers covering the gastric mucosa
      were differently regulated. Luminal administration of PGE(2) increased the
      thickness of both layers, whereas luminal NO stimulated only firmly adherent
      mucus accumulation. A new gastroprotective role for iNOS was indicated since iNOS
      deficient mice had thinner firmly adherent mucus layers and a lower mucus
      accumulation rate, whereas nNOS did not appear to be involved in mucus secretion.
      Downregulation of gastric mucus accumulation was observed in Muc1-/- mice. Both
      the firmly and loosely adherent mucus layers consisted of Muc5ac mucins. In
      conclusion, this study showed that, even though both the two mucus layers
      covering the gastric mucosa consist of Muc5ac, they are differently regulated by
      luminal PGE(2) and NO. A new gastroprotective role for iNOS was indicated since
      iNOS-/- mice had a thinner firmly adherent mucus layer. In addition, a regulatory
      role of Muc1 was demonstrated since downregulation of gastric mucus accumulation
      was observed in Muc1-/- mice.

PMID- 18719001
TI  - Mice lacking the Na+/H+ exchanger 2 have impaired recovery of intestinal barrier
      function.
AB  - Ischemic injury induces breakdown of the intestinal barrier. Recent studies in
      porcine postischemic tissues indicate that inhibition of NHE2 results in enhanced
      recovery of barrier function in vitro via a process involving interepithelial
      tight junctions. To further study this process, recovery of barrier function was
      assessed in wild-type (NHE2(+/+)) and NHE2(-/-) mice in vivo and wild-type mice
      in vitro. Mice were subjected to complete mesenteric ischemia in vivo, after
      which barrier function was measured by blood-to-lumen mannitol clearance over a 3
      h recovery period or measurement of transepithelial electrical resistance (TER)
      in Ussing chambers immediately following ischemia. Tissues were assessed for
      expression of select junctional proteins. Compared with NHE2(+/+) mice, NHE2(-/-)
      mice had greater intestinal permeability during the postischemic recovery
      process. In contrast to prior porcine studies, pharmacological inhibition of NHE2
      in postischemic tissues from wild-type mice also resulted in significant
      reductions in TER. Mucosa from NHE2(-/-) mice displayed a shift of occludin and
      claudin-1 expression to the Triton-X-soluble membrane fractions and showed
      disruption of occludin and claudin-1 localization patterns following injury. This
      was qualitatively and quantitatively recovered in NHE2(+/+) mice compared with
      NHE2(-/-) mice by the end of the 3-h recovery period. Serine phosphorylation of
      occludin and claudin-1 was downregulated in NHE2(-/-) postischemia compared with
      wild-type mice. These data indicate an important role for NHE2 in recovery of
      barrier function in mice via a mechanism involving tight junctions.

PMID- 18719002
TI  - Gastrin increases mcl-1 expression in type I gastric carcinoid tumors and a
      gastric epithelial cell line that expresses the CCK-2 receptor.
AB  - Elevated serum concentrations of the hormone gastrin are associated with the
      development of gastric carcinoid tumors, but the mechanisms of tumor development
      are not fully understood. We hypothesized that the antiapoptotic effects of
      gastrin may be implicated and have therefore investigated the role of
      antiapoptotic members of the bcl-2 family of proteins. AGS-G(R) human gastric
      carcinoma cells stably transfected with the CCK-2 receptor were used to assess
      changes in the expression of bcl-2 family members following gastrin treatment and
      the function of mcl-1 during apoptosis was investigated by use of small
      interfering RNA (siRNA). Treatment of AGS-G(R) cells with 10 nM gastrin for 6 h
      caused maximally increased mcl-1 protein abundance. Gastrin-induced mcl-1
      expression was inhibited by the transcription inhibitor actinomycin D and by the
      protein synthesis inhibitor cycloheximide. Downstream signaling of mcl-1
      expression occurred via the CCK-2 receptor, protein kinase C, and MAP kinase
      pathways, but not via PI 3-kinase. Transfection with mcl-1 siRNA significantly
      suppressed mcl-1 protein expression and abolished the antiapoptotic effects of
      gastrin on serum starvation-induced apoptosis. Mcl-1 protein expression was also
      specifically increased in the type I enterochromaffin-like cell carcinoid tumors
      of 10 patients with autoimmune atrophic gastritis and hypergastrinemia. Gastrin
      therefore signals via the CCK-2 receptor, protein kinase C, and MAP kinase to
      induce expression of antiapoptotic mcl-1 in AGS-G(R) cells, and mcl-1 expression
      is also increased in human hypergastrinemia-associated type I gastric carcinoid
      tumors. Gastrin-induced mcl-1 expression may therefore be an important mechanism
      contributing toward type I gastric carcinoid development.

PMID- 18719003
TI  - In vitro optimization of dexamethasone phosphate delivery by iontophoresis.
AB  - BACKGROUND AND PURPOSE: This study was designed to evaluate the effects of
      competing ions and electroosmosis on the transdermal iontophoresis of
      dexamethasone phosphate (Dex-Phos) and to identify the optimal conditions for its
      delivery. METHODS: The experiments were performed using pig skin, in side-by-side
      diffusion cells (0.78 cm(2)), passing a constant current of 0.3 mA via Ag-AgCl
      electrodes. Dex-Phos transport was quantified for donor solutions (anodal and
      cathodal) containing different drug concentrations, with and without background
      electrolyte. Electrotransport of co-ion, citrate, and counterions Na(+) and K(+)
      also was quantified. The contribution of electroosmosis was evaluated by
      measuring the transport of the neutral marker (mannitol). RESULTS:
      Electromigration was the dominant mechanism of drug iontophoresis, and reduction
      in electroosmotic flow directed against the cathodic delivery of Dex-Phos did not
      improve drug delivery. The Dex-Phos flux from the cathode was found to be optimal
      (transport number of approximately 0.012) when background electrolyte was
      excluded from the formulation. In this case, transport of the drug is limited
      principally by the competition with counterions (mainly Na(+) with a transport
      number of approximately 0.8) and the mobility of the drug in the membrane.
      DISCUSSION AND CONCLUSION: Dex-Phos must be delivered from the cathode and
      formulated rationally, excluding mobile co-anions, to achieve optimal
      iontophoretic delivery.

PMID- 18719004
TI  - Meaning of caring to 7 novice physical therapists during their first year of
      clinical practice.
AB  - BACKGROUND AND PURPOSE: Caring has been identified as a rules-based approach to
      good patient care, as a core value in physical therapist professional behavior,
      as a part of experienced and expert practice, as a virtue, and as a moral
      orientation. Previous research showed that experienced and expert female physical
      therapists value compassion and caring in clinical practice. However, little is
      known about how novice physical therapists care for their patients. The purpose
      of this study was to explore the meaning of caring from the perspectives of
      novice physical therapists. SUBJECTS: Seven novice physical therapists (with less
      than 1 year of clinical experience) working in either an outpatient or an
      inpatient facility were recruited. METHODS: A qualitative method (phenomenology)
      was used, with data being obtained from retrospective interviews of the novice
      physical therapists regarding their experiences in the clinic. RESULTS: Three
      common themes relating to the nature of caring emerged: learning to care (with
      the following subthemes: barriers to caring, the "difficult" patient, finding a
      balance, and time constraints), patients as subjects, and the culture of the
      clinic. DISCUSSION AND CONCLUSION: The novice physical therapists in this study
      expressed difficulty in dealing with difficult patients, with time management,
      and with balancing their professional and personal lives. However, despite the
      barriers to caring, many of these participants viewed caring not just as a rules
      based approach but as a core value and, in some cases, a moral orientation that
      guided their first year of clinical practice. The findings suggest that caring
      requires certain skills and attitudes that accrue over time and that physical
      therapist education programs should integrate learning experiences (including
      clinical experiences) throughout the curriculum that foster caring behaviors in
      order to prepare students for the first-year transition in the clinic. In
      addition, experienced clinicians should appreciate how their clinic's culture and
      their behaviors can help model caring attitudes in novice physical therapists.

PMID- 18719005
TI  - Gait variability in older adults: observational rating validated by comparison
      with a computerized walkway gold standard.
AB  - BACKGROUND AND PURPOSE: Gait variability has been measured with computerized
      technology-intensive techniques, which are not practical in clinical settings.
      The purpose of this study was to validate an observational rating of gait
      variability for routine clinical practice. SUBJECTS: Community-dwelling older
      adults aged 65 years and older (n=46; mean age=81.2 years, SD=6.8 years, range=66
      91 years) participated in this study. METHODS: The standard deviation of stance
      time (stance time variability) derived from gait characteristics recorded by use
      of a computerized walkway was used as the gold standard for gait variability. The
      validity of the diagnostic test evaluated in this study (an observational rating
      of gait variability) was determined by comparison with the quantitative measure
      of stance time variability. RESULTS: Six validity indexes were defined for the
      observational rating of gait variability: sensitivity=81%; specificity=53%;
      positive predictive value=65%; negative predictive value=71%; positive likelihood
      ratio=1.72; and negative likelihood ratio=0.36. DISCUSSION AND CONCLUSION: An
      observational rating of gait variability was validated by comparison with stance
      time variability derived from a computerized walkway. The concurrent validity of
      the 2 methods of determining gait variability provides support for the use of the
      observational rating as an alternative measure of gait variability for the
      purpose of identifying older adults at risk for mobility disability in clinical
      settings.

PMID- 18719006
TI  - Will European agricultural policy for school fruit and vegetables improve public
      health? A review of school fruit and vegetable programmes.
AB  - BACKGROUND: For the first time, public health, particularly obesity, is being
      seen as a driver of EU agricultural policy. In 2007, European Ministers of
      Agriculture were asked to back new proposals for school fruit and vegetable
      programmes as part of agricultural reforms. In 2008, the European Commission
      conducted an impact assessment to assess the potential impact of this new
      proposal on health, agricultural markets, social equality and regional cohesion.
      METHODS: A systematic review of the effectiveness of interventions to promote
      fruit and/or vegetable consumption in children in schools, to inform the EC
      policy development process. RESULTS: School schemes are effective at increasing
      both intake and knowledge. Of the 30 studies included, 70% increased fruits and
      vegetables (FV) intake, with none decreasing intake. Twenty-three studies had
      follow-up periods >1 year and provide some evidence that FV schemes can have long
      term impacts on consumption. Only one study led to both increased fruit and
      vegetable intake and reduction in weight. One study showed that school fruit and
      vegetable schemes can also help to reduce inequalities in diet. Effective school
      programmes have used a range of approaches and been organized in ways which vary
      nationally depending on differences in food supply chain and education systems.
      CONCLUSIONS: EU agriculture policy for school fruits and vegetables schemes
      should be an effective approach with both public health and agricultural
      benefits. Aiming to increase FV intake amongst a new generation of consumers, it
      will support a range of EU policies including obesity and health inequalities.

PMID- 18719007
TI  - Collection of data on ethnic origin in England.

PMID- 18719008
TI  - Truly independent research?

PMID- 18719009
TI  - Obesity in children.

PMID- 18719010
TI  - Should we prescribe diuretics for patients with prediabetes and hypertension?

PMID- 18719011
TI  - Do overweight children necessarily make overweight adults? Repeated cross
      sectional annual nationwide survey of Japanese girls and women over nearly six
      decades.
AB  - OBJECTIVE: To compare growth curves of body mass index from children to
      adolescents, and then to young adults, in Japanese girls and women in birth
      cohorts born from 1930 to 1999. DESIGN: Retrospective repeated cross sectional
      annual nationwide surveys (national nutrition survey, Japan) carried out from
      1948 to 2005. SETTING: Japan. PARTICIPANTS: 76,635 females from 1 to 25 years of
      age. MAIN OUTCOME MEASURE: Body mass index. RESULTS: Generally, body mass index
      decreased in preschool children (2-5 years), increased in children (6-12 years)
      and adolescents (13-18 years), and slightly decreased in young adults (19-25
      years) in these Japanese females. However, the curves differed among birth
      cohorts. More recent cohorts were more overweight as children but thinner as
      young women. The increments in body mass index in early childhood were larger in
      more recent cohorts than in older cohorts. However, the increments in body mass
      index in adolescents were smaller and the decrease in body mass index in young
      adults started earlier, with lower peak values in more recent cohorts than in
      older cohorts. The decrements in body mass index in young adults were similar in
      all birth cohorts. CONCLUSIONS: An overweight birth cohort in childhood does not
      necessarily continue to be overweight in young adulthood. Not only secular trends
      in body mass index at fixed ages but also growth curves for wide age ranges by
      birth cohorts should be considered to study obesity and thinness. Growth curves
      by birth cohorts were produced by a repeated cross sectional annual survey over
      nearly six decades.

PMID- 18719012
TI  - Hypercholesterolaemia and its management.

PMID- 18719015
TI  - Australia to try US-style physician assistants.

PMID- 18719013
TI  - Health related quality of life after combined hormone replacement therapy:
      randomised controlled trial.
AB  - OBJECTIVE: To assess the effect of combined hormone replacement therapy (HRT) on
      health related quality of life. DESIGN: Randomised placebo controlled double
      blind trial. SETTING: General practices in United Kingdom (384), Australia (94),
      and New Zealand (24). PARTICIPANTS: Postmenopausal women aged 50-69 at
      randomisation; 3721 women with a uterus were randomised to combined oestrogen and
      progestogen (n=1862) or placebo (n=1859). Data on health related quality of life
      at one year were available from 1043 and 1087 women, respectively. INTERVENTIONS:
      Conjugated equine oestrogen 0.625 mg plus medroxyprogesterone acetate 2.5/5.0 mg
      or matched placebo orally daily for one year. MAIN OUTCOME MEASURES: Health
      related quality of life and psychological wellbeing as measured by the women's
      health questionnaire. Changes in emotional and physical menopausal symptoms as
      measured by a symptoms questionnaire and depression by the Centre for
      Epidemiological Studies depression scale (CES-D). Overall health related quality
      of life and overall quality of life as measured by the European quality of life
      instrument (EuroQol) and visual analogue scale, respectively. RESULTS: After one
      year small but significant improvements were observed in three of nine components
      of the women's health questionnaire for those taking combined HRT compared with
      those taking placebo: vasomotor symptoms (P<0.001), sexual functioning (P<0.001),
      and sleep problems (P<0.001). Significantly fewer women in the combined HRT group
      reported hot flushes (P<0.001), night sweats (P<0.001), aching joints and muscles
      (P=0.001), insomnia (P<0.001), and vaginal dryness (P<0.001) than in the placebo
      group, but greater proportions reported breast tenderness (P<0.001) or vaginal
      discharge (P<0.001). Hot flushes were experienced in the combined HRT and placebo
      groups by 30% and 29% at trial entry and 9% and 25% at one year, respectively. No
      significant differences in other menopausal symptoms, depression, or overall
      quality of life were observed at one year. CONCLUSIONS: Combined HRT started many
      years after the menopause can improve health related quality of life. TRIAL
      REGISTRATION: ISRCTN 63718836.

PMID- 18719016
TI  - Dynamics of lung macrophage activation in response to helminth infection.
AB  - Most of our understanding of the development and phenotype of alternatively
      activated macrophages (AAMs) has been obtained from studies investigating the
      response of bone marrow- and peritoneal-derived cells to IL-4 or IL-13
      stimulation. Comparatively little is known about the development of AAMs in the
      lungs, and how the complex signals associated with pulmonary inflammation
      influence the AAM phenotype. Here, we use Nippostrongylus brasiliensis to
      initiate AAM development and define the dynamics of surface molecules, gene
      expression, and cell function of macrophages isolated from lung tissue at
      different times postinfection (PI). Initially, lung macrophages take on a foamy
      phenotype, up-regulate MHC and costimulatory molecules, express reduced levels of
      TNF and IL-12, and undergo proliferation. Cells isolated between days 8 and 15 PI
      adopt a dense, granular phenotype and exhibit reduced levels of costimulatory
      molecules and elevated levels of programmed death ligand-1 (PDL-1) and PDL-2 and
      an increase in IL-10 expression. Functionally, AAMs isolated on days 13-15 PI
      demonstrate an enhanced capacity to take up and sequester antigen. However, these
      same cells did not mediate antigen-specific T cell proliferation and dampened the
      proliferation of CD3/CD28-activated CD4+ T cells. These data indicate that the
      alternative activation of macrophages in the lungs, although initiated by IL-4/IL
      13, is a dynamic process that is likely to be influenced by other immune and
      nonimmune factors in the pulmonary environment.

PMID- 18719017
TI  - A novel subset of NK cells expressing high levels of inhibitory FcgammaRIIB
      modulating antibody-dependent function.
AB  - NK cells can kill antibody-coated target cells following engagement of
      FcgammaRIIIA, the major activating FcgammaR expressed by these cells. The
      presence of FcgammaRIIC (CD32C) has also been reported, but its contribution to
      the FcgammaR-dependent effector functions of NK cells remains debated. We
      demonstrate here that inhibitory FcgammaRIIB is also expressed by a small subset
      of CD56+/NKp46+ NK cells and can efficiently down-modulate their FcgammaR
      dependent effector function. Immunofluorescence analyses of NK cells from 52
      healthy donors showed the presence of CD56bright/FcgammaRII(-) (5.2%+/-3.4),
      CD56dim/FcgammaRII(lo/-) (94.1%+/-3.4), and CD56dim/FcgammaRIIbright (0.64%+/
      0.72) cells. QRT-PCR and protein analyses performed on isolated FcgammaRIIbright
      NK cells indicated that FcgammaRIIB is strongly expressed by these cells but not
      by FcgammaRII(lo/-) cells. In addition, FcgammaRIIbright cells showed a weaker
      antibody-dependent degranulation when incubated with IgG-coated target cells
      compared with FcgammaRII(lo/-) NK cells, although a strong FcgammaRIIIA
      expression was detected in both cells. Furthermore, the addition of anti
      FcgammaRII Fab paralleled a higher degranulation of FcgammaRIIbright NK cells,
      indicating a direct role for FcgammaRIIB in this down-modulating effect. Thus, it
      is proposed that FcgammaRIIBbright NK cells represent a new NK cell compartment
      able to down-modulate NK cell functions triggered by the engagement of activating
      FcgammaR.

PMID- 18719019
TI  - Suppression of basal spontaneous gonadotropin-releasing hormone neuronal activity
      during lactation: role of inhibitory effects of neuropeptide Y.
AB  - Increased neuropeptide Y (NPY) activity drives the chronic hyperphagia of
      lactation and may contribute to the suppression of GnRH activity. The majority of
      GnRH neurons are contacted by NPY fibers, and GnRH cells express NPY Y5 receptor
      (Y5R). Therefore, NPY provides a neurocircuitry for information about food
      intake/energy balance to be directly transmitted to GnRH neurons. To investigate
      the effects of lactation on GnRH neuronal activity, hypothalamic slices were
      prepared from green fluorescent protein-GnRH transgenic rats. Extracellular loose
      patch recordings determined basal GnRH neuronal activity from slices of
      ovariectomized control and lactating rats. Compared with controls, hypothalamic
      slices from lactating rats had double the number of quiescent GnRH neurons (14.51
      +/- 2.86 vs. 7.04 +/- 2.84%) and significantly lower firing rates of active GnRH
      neurons (0.25 +/- 0.02 vs. 0.37 +/- 0.03 Hz). To study the NPY-postsynaptic Y5R
      system, whole-cell current-clamp recordings were performed in hypothalamic slices
      from control rats to examine NPY/Y5R antagonist effects on GnRH neuronal resting
      membrane potential. Under tetrodotoxin treatment, NPY hyperpolarized GnRH neurons
      from -56.7 +/- 1.94 to -62.1 +/- 1.83 mV; NPY's effects were blocked by Y5R
      antagonist. To determine whether increased endogenous NPY tone contributes to
      GnRH neuronal suppression during lactation, hypothalamic slices were treated with
      Y5R antagonist. A significantly greater percentage of GnRH cells were activated
      in slices from lactating rats (52%) compared with controls (28%). These results
      suggest that: 1) basal GnRH neuronal activity is suppressed during lactation; 2)
      NPY can hyperpolarize GnRH neurons via postsynaptic Y5R; and 3) increased
      inhibitory NPY tone during lactation is a component of the mechanisms responsible
      for suppression of GnRH neuronal activity.

PMID- 18719020
TI  - Characterization of thyrotropin receptor antibody-induced signaling cascades.
AB  - The TSH receptor (TSHR) is constitutively active and is further enhanced by TSH
      ligand binding or by stimulating TSHR antibodies (TSHR-Abs) as seen in Graves'
      disease. TSH is known to activate the thyroid epithelial cell via both Galphas
      cAMP/protein kinase A/ERK and Galphaq-Akt/protein kinase C coupled signaling
      networks. The recent development of monoclonal antibodies to the TSHR has enabled
      us to investigate the hypothesis that different TSHR-Abs may have unique
      signaling imprints that differ from TSH ligand itself. We have, therefore,
      performed sequential studies, using rat thyrocytes (FRTL-5, passages 5-20) as
      targets, to examine the signaling pathways activated by a series of monoclonal
      TSHR-Abs in comparison with TSH itself. Activation of key signaling molecules was
      estimated by specific immunoblots and/or enzyme immunoassays. Continuing
      constitutive TSHR activity in thyroid cells, deprived of TSH and serum for 48 h,
      was demonstrated by pathway-specific chemical inhibition. Under our experimental
      conditions, TSH ligand and TSHR-stimulating antibodies activated both Galphas and
      Galphaq effectors. Importantly, some TSHR-blocking and TSHR-neutral antibodies
      were also able to generate signals, influencing primarily the Galphaq effectors
      and induced cell proliferation. Most strikingly, antibodies that used the Galphaq
      cascades used c-Raf-ERK-p90RSK as a unique signaling cascade not activated by
      TSH. Our study demonstrated that individual TSHR-Abs had unique molecular
      signatures which resulted in sequential preferences. Because downstream thyroid
      cell signaling by the TSHR is both ligand dependent and independent, this may
      explain why TSHR-Abs are able to have variable influences on thyroid cell
      biology.

PMID- 18719021
TI  - Pharmacological demarcation of the growth hormone, gut motility and feeding
      effects of ghrelin using a novel ghrelin receptor agonist.
AB  - The peptide hormone ghrelin exerts a wide spectrum of activities including the
      stimulation of GH release, feeding, and gastrointestinal motility, purportedly
      via the activation of a common receptor, GH secretagogue receptor (since renamed
      the GRLN-R) The aim of the present study was to determine whether these effects
      can be separated pharmacologically. Tranzyme Pharma (TZP)-101 is a small-molecule
      agonist with potent binding affinity (inhibitory constant = 16 nm) and full
      agonist activity (EC50 = 29 nm, maximum response = 111%) at the human recombinant
      GRLN-R. Pharmacokinetic profiling of TZP-101 in rat determined a plasma
      elimination half-life of 99 min and low blood-brain barrier permeability (0.09%).
      The pharmacological response to TZP-101, administered centrally
      [intracerebroventricular (icv)] or peripherally (iv), was evaluated in comparison
      with that of acylated ghrelin. Thus, TZP-101 (iv) accelerated gastric emptying of
      a liquid meal (2% methylcellulose) similarly to ghrelin (iv). IAlso, TZP-101
      (icv) stimulated spontaneous, cumulative food intake in a similar manner to
      ghrelin (icv). However, unlike ghrelin, TZP-101 did not elicit significant GH
      release on either central or peripheral administration. Moreover, TZP-101 did not
      alter ghrelin-induced GH release. n total, these data demonstrate that the GH
      response can be pharmacologically demarcated from the orexigenic and
      gastrointestinal responses to ghrelin in rats. The observation that the centrally
      mediated orexigenic response and the peripherally mediated gastric motility
      response are pharmacologically associated is consistent with the classification
      of ghrelin as a brain-gut peptide, whereas the additional action of ghrelin to
      stimulate GH release (possibly via a distinct signaling pathway) may be
      considered a complementary mechanism to harmonize somatic growth and body
      composition with the regulation of energy homeostasis.

PMID- 18719018
TI  - Insulin-like growth factors in the peripheral nervous system.
AB  - IGF-I and -II are potent neuronal mitogens and survival factors. The actions of
      IGF-I and -II are mediated via the type I IGF receptor (IGF-IR) and IGF binding
      proteins regulate the bioavailability of the IGFs. Cell viability correlates with
      IGF-IR expression and intact IGF-I/IGF-IR signaling pathways, including
      activation of MAPK/phosphatidylinositol-3 kinase. The expression of IGF-I and 
      II, IGF-IR, and IGF binding proteins are developmentally regulated in the central
      and peripheral nervous system. IGF-I therapy demonstrates mixed therapeutic
      results in the treatment of peripheral nerve injury, neuropathy, and motor neuron
      diseases such as amyotrophic lateral sclerosis. In this review we discuss the
      role of IGFs during peripheral nervous system development and the IGF signaling
      system as the potential therapeutic target for the treatment of nerve injury and
      motor neuron diseases.

PMID- 18719022
TI  - Mice lacking the thyroid hormone receptor-alpha gene spend more energy in
      thermogenesis, burn more fat, and are less sensitive to high-fat diet-induced
      obesity.
AB  - Unable to activate brown adipose tissue (BAT) thermogenesis, alphaT3-receptor
      deficient mice (Thra-0/0) are cold intolerant. Our objective was to investigate
      the impact on energy economy and mechanisms of the alternate facultative
      thermogenesis developed. Energy expenditure (oxygen and food consumption) is
      elevated in Thra-0/0 mice reared at room temperature. Such difference disappears
      at thermoneutrality (30 C) and expands as ambient temperature becomes colder (P <
      0.001). Despite eating more, Thra-0/0 are leaner than wild-type (WT) mice (P <
      0.01), whereas these, whether on chow or high-fat diet, gained more weight (g/d:
      0.12 +/- 0.002 vs. 0.08 +/- 0.002 and 0.25 +/- 0.005 vs. 0.17 +/- 0.005,
      respectively) and adiposity than Thra-0/0 mice (P < 0.001). The respiratory
      quotient was lower in Thra-0/0 than WT mice (P < 0.001), after feeding or fasted,
      on chow or high-fat diet, indicating a preference for fat as fuel, which was
      associated with increased lipoprotein lipase (LPL) expression in skeletal muscle
      of Thra-0/0 mice but with no differences in gene expression in white adipose
      tissue. Type-2 deiodinase (D2) was increased in BAT and aerobic muscle of Thra
      0/0 mice. This and liver D1 were increased by a high-fat diet in both genotypes,
      as also were serum T3 and T3/T4 ratio, but more in Thra-0/0 than WT mice (P <
      0.001). Remarkably, when studied at thermoneutrality, genotype differences in
      weight and adiposity gain, respiratory quotient, D2, and LPL disappeared. Thus,
      disruption of BAT thermogenesis in Thra-0/0 mice activates an alternate
      facultative thermogenesis that is more energy demanding and associated with
      reduced fuel efficiency, leanness, increased capacity to oxidize fat, and
      relative resistance to diet-induced obesity, in all of which muscle LPL and
      deiodinases play a key role.

PMID- 18719023
TI  - EGCG stabilizes p27kip1 in E2-stimulated MCF-7 cells through down-regulation of
      the Skp2 protein.
AB  - Loss of p27Kip1 is associated with a poor prognosis in breast cancer. According
      to previous findings, a decrease in p27Kip1 levels is mainly the result of
      enhanced proteasome-dependent degradation mediated by its specific ubiquitin
      ligase subunit S-phase kinase protein 2 (Skp2). Epigallocatechin-3-gallate
      (EGCG), the main constituent of green tea, was found to stabilize p27Kip1 levels
      in breast cancer, but whether this effect is mediated through changes in Skp2
      expression remains unclear. Here we investigated the mechanisms involved in
      EGCG's growth inhibition of estrogen-responsive human breast cancer MCF-7 cells.
      In our results, EGCG increased p27Kip1 and decreased Skp2 in a time- and dose
      dependent manner, suggesting that p27Kip1 and Skp2 may be involved in the growth
      inhibition by EGCG in estrogen-stimulated MCF-7 cells. Interestingly, mRNA levels
      of p27Kip1 and Skp2 did not significantly change in estrogen-stimulated MCF-7
      cells after EGCG treatments. Moreover, overexpression of Skp2 in MCF-7 cells
      prevented accumulation of p27Kip1 and promoted resistance to the
      antiproliferative effects of EGCG. This suggests that the down-regulation of the
      F-box protein Skp2 is the mechanism underlying p27Kip1 accumulation. Furthermore,
      both tamoxifen and paclitaxel significantly and synergistically enhanced the
      growth inhibition of MCF-7 cells by EGCG through the down-regulation of Skp2
      protein. However, the down-regulation of Skp2 was not always correlate with the
      up-regulation of p27, suggesting that EGCG-dependent Skp2 down-regulation can
      influence cell growth in several ways. The therapeutic strategies designed to
      reduce Skp2 may therefore play an important clinical role in treatment of breast
      cancer cells.

PMID- 18719024
TI  - Expression of the transcriptional repressor ATF3 in gonadotrophs is regulated by
      Egr-1, CREB, and ATF2 after gonadotropin-releasing hormone receptor stimulation.
AB  - Stimulation of GnRH receptors enhances expression of activating transcription
      factor (ATF) 3 in a pituitary gonadotroph cell line. The signaling pathway
      requires elevated cytosolic Ca2+ levels and activation of ERK and c-Jun N
      terminal protein kinase. The signaling cascade was blocked by overexpression of
      either MAPK phosphatase (MKP)-1 or MAPK phosphatase-5 that dephosphorylate
      nuclear ERK and c-Jun N-terminal protein kinase. In addition, ATF3 biosynthesis
      was impaired after lentiviral-mediated expression of a constitutively active
      mutant of calcineurin A. Thus, MKP-1, MKP-5, and calcineurin may function as shut
      off devices for GnRH receptor signaling. Expression of dominant-negative mutants
      of early growth response protein (Egr)-1, cAMP response element binding protein
      (CREB), and ATF2 blocked the biosynthesis of ATF3, indicating that these
      transcription factors connect the intracellular signaling cascade elicited by
      activation of GnRH receptors with transcription of the ATF3 gene. This view was
      corroborated by chromatin immunoprecipitation experiments revealing that Egr-1
      and the phosphorylated forms of CREB and ATF2 bound to the 5'-upstream region of
      the ATF3 gene in buserelin-stimulated gonadotrophs. Together the data indicate
      that the ATF3 gene is a bona fide target gene of Egr-1, CREB, and ATF2 in
      gonadotrophs. Moreover, we show that in gonadotrophs ATF3 bound to its own
      promoter under physiological conditions. The analysis of a lentiviral-transmitted
      ATF3 promoter/luciferase reporter gene, embedded into the chromatin of the cells,
      revealed that ATF3 blocked the activity of its own promoter. We additionally
      identified the chromogranin B gene as bona fide target gene of ATF3 in
      gonadotrophs.

PMID- 18719025
TI  - Estrogen actions in the male reproductive system involve estrogen response
      element-independent pathways.
AB  - The estrogen receptor-alpha (ERalpha) acts through multiple pathways, including
      estrogen response element (ERE)-dependent (classical) and ERE-independent
      (nonclassical) mechanisms. We previously created a mouse model harboring a two
      amino-acid mutation of the DNA-binding domain (E207A, G208A) that precludes
      direct binding of ERalpha to an ERE. After crossing heterozygous mutant mice with
      an ERalpha knockout (ERKO) line, it was possible to assess the degree of
      physiological rescue by the isolated ERalpha nonclassical allele (-/AA; AA) when
      compared with ERKO mice (-/-) and to wild type (+/+; WT). In male ERKO mice up to
      8 months of age, testosterone levels were high, although LH levels were similar
      to WT. Testosterone was normal in the AA mice, indicating that the AA allele
      rescues the enhanced testosterone biosynthesis in ERKO mice. Male ERKO mice
      exhibited distention of the seminiferous tubules as early as 2-3 months of age as
      a consequence of decreased water resorption in the efferent ducts. By 3-4 months
      of age, ERKO mice had impaired spermatogenesis in approximately 40% of their
      tubules, and sperm counts and motility declined in association with the
      histological changes. In the AA mice, histological defects were greatly reduced
      or absent, and sperm counts and motility were rescued. Levels of aquaporins 1 and
      9, which contribute to water uptake in the efferent ducts, were reduced in ERKO
      mice and partially or fully rescued in AA mice, whereas another water
      transporter, sodium-hydrogen exchanger-3, was decreased in both ERKO and AA mice.
      We conclude that non-ERE-dependent estrogen pathways are sufficient to rescue the
      defective spermatogenesis observed in ERKO mice and play a prominent role in
      ERalpha action in the testis, including pathways that regulate water resorption
      and androgen biosynthesis.

PMID- 18719026
TI  - Nuclear factor-kappaB mediates the inhibitory effects of tumor necrosis factor
      alpha on growth hormone-inducible gene expression in liver.
AB  - TNF inhibits serine protease inhibitor 2.1 (Spi 2.1) and IGF-I gene expression by
      GH in CWSV-1 hepatocytes. The current study describes construction of a GH
      inducible IGF-I promoter construct and investigates mechanisms by which TNF and
      nuclear factor-kappaB (NFkappaB) inhibit GH-inducible gene expression. CWSV-1
      cells were transfected with GH-inducible Spi 2.1 or IGF-I promoter luciferase
      constructs, incubated with TNF signaling inhibitors (fumonisin B1 for
      sphingomyelinase and SP600125 for c-Jun N-terminal kinase), treated with or
      without TNF, and then stimulated with recombinant human GH. The 5- to 6-fold
      induction of Spi 2.1 and IGF-I promoter activity by GH was inhibited by TNF.
      Neither fumonisin B1 nor SP600125 prevented the inhibitory effects of TNF on GH
      inducible promoter activity. Dominant-negative inhibitor-kappaBalpha
      (IkappaBalpha) expression vectors (IkappaBalphaS/A or IkappaBalphaTrunc), p65 and
      p50 expression vectors, and p65 deletion constructs were used to investigate the
      NFkappaB pathway. IkappaBalphaS/A and IkappaBalphaTrunc ameliorated the
      inhibitory effects of TNF on GH-inducible Spi 2.1 and IGF-I promoter activity.
      Cotransfection of CWSV-1 cells with expression vectors for p65 alone or p50 and
      p65 together inhibited GH-inducible Spi 2.1 and IGF-I promoter activity.
      Cotransfection with a C-terminal p65 deletion (1-450) enhanced GH-inducible
      promoter activity, whereas the N-terminal deletion (31-551) was inhibitory for
      IGF-I but not Spi 2.1. Cycloheximide did not antagonize the inhibitory effects of
      TNF on GH-inducible IGF-I expression. We conclude the inhibitory effects of TNF
      on GH-inducible promoter activity are mediated by NFkappaB, especially p65, by a
      mechanism that does not require protein synthesis.

PMID- 18719027
TI  - Urocortin 1 inhibits rat leydig cell function.
AB  - Corticotropin-releasing factor (CRF) has previously been reported in rat testes
      in which it inhibits Leydig cells activity. However, recent studies in our
      laboratory have suggested that some of the effects originally attributed to CRF
      were instead due to the related peptide Urocortin 1 (Ucn 1) and that this latter
      hormone, not CRF, was detectable in Leydig cells. We show here that Ucn 1 [a
      mixed CRF receptor (CRFR) type 1 and CRFR2 agonist] and the CRFR1-selective
      peptide Stressin 1, but not Ucn 2 or Ucn 3 (both considered selective CRFR2
      ligands), significantly blunt the testosterone response to human chorionic
      gonadotropin. The effect of Ucn 1 is observed regardless of whether this peptide
      is injected iv or directly into the testes, and it is reversed by the mixed
      CRFR1/R2 antagonist Astressin B. Blockade of GnRH receptors with the antagonist
      Azalin B does not interfere with the influence of Ucn 1, thereby demonstrating
      that pituitary luteinizing hormone does not appear to be involved in this model.
      Collectively these results suggest that Ucn 1, not CRF, is present in the rat
      testes and interferes with Leydig cell activity. However, whereas we previously
      reported that alcohol up-regulated gonadal Ucn 1 gene expression, CRF receptor
      antagonists were unable to reverse the inhibitory effect exerted by alcohol on
      human chorionic gonadotropin-induced testosterone release. The functional role
      played by testicular Ucn 1 in stress models characterized by blunted androgen
      levels therefore needs to be further investigated.

PMID- 18719028
TI  - Beta-adrenergic receptor mediated protection against doxorubicin-induced
      apoptosis in cardiomyocytes: the impact of high ambient glucose.
AB  - Recent studies have demonstrated that the beta2-adrenergic receptor (beta2AR)
      Galphai signaling pathway exerts a cardiac antiapoptotic effect. The goals of
      this study were to determine the intracellular signaling factors involved in
      beta2AR-mediated protection against doxorubicin-induced apoptosis in H9c2
      cardiomyocyte and explore the impact of high ambient glucose on the antiapoptotic
      effect. Under physiological glucose environment (100 mg/dl), beta2AR stimulation
      prevented doxorubicin-induced apoptosis, which was attenuated by cotreatment with
      wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, or transfection of a
      dominant-negative Akt. Inhibition of Src kinase with 4-amino-5-(4-chlorophenyl)-7
      (t-butyl)pyrazolo[3,4-d] pyrimidine or cSrc small interfering RNA 32 also
      attenuated the antiapoptotic effect. Inhibition of platelet-derived growth factor
      receptor (PDGFR) with AG1296 reversed the beta2AR-induced antiapoptotic effect.
      Transfection of an active Src cDNA (Y529F) alone was sufficient to render the
      cells resistant to apoptosis, and the resistance was blocked by wortmannin.
      Transfection of an active PI3K minigene (iSH2-p110) alone also induced resistance
      to apoptosis, and the resistance was reversed by an Akt-inhibitor but not by
      AG1296. High ambient glucose (450 mg/dl) caused two major effects: 1) it
      significantly reduced betaAR-induced PDGFR phosphorylation, Src kinase activity,
      and activation of PI3K signaling pathway; and 2) it partially attenuated beta2AR
      induced antiapoptotic effect. These data provide in vitro evidence supporting a
      signaling cascade by which beta2AR exerts a protective effect against doxorubicin
      induced apoptosis via sequential involvement of Galphai, Gbetagamma, Src, PDGFR,
      PI3K, and Akt. High ambient glucose significantly attenuates beta2AR-mediated
      cardioprotection by suppressing factors involved in this cascade including PDGFR,
      Src, and PI3K/Akt.

PMID- 18719029
TI  - Diffusion tensor MR imaging in chronic spinal cord injury.
AB  - BACKGROUND AND PURPOSE: Diffusion tensor MR imaging is emerging as an important
      tool for displaying anatomic changes in the brain after injury or disease but has
      been less widely applied to disorders of the spinal cord. The aim of this study
      was to characterize the diffusion properties of the entire human spinal cord in
      vivo during the chronic stages of spinal cord injury (SCI). These data provide
      insight into the structural changes that occur as a result of long-term recovery
      from spinal trauma. MATERIALS AND METHODS: Thirteen neurologically intact
      subjects and 10 subjects with chronic SCI (>4 years postinjury) were enrolled in
      this study. A single-shot twice-refocused spin-echo diffusion-weighted echo
      planar imaging pulse sequence was used to obtain axial images throughout the
      entire spinal cord (C1-L1) in <60 minutes. RESULTS: Despite heterogeneity in SCI
      lesion severity and location, diffusion characteristics of the chronic lesion
      were significantly elevated compared with those of uninjured controls. Fractional
      anisotropy was significantly lower at the chronic lesion and appeared dependent
      on the completeness of the injury. Conversely, mean diffusivity measurements in
      the upper cervical spinal cord in subjects with SCI were significantly lower than
      those in controls. These trends suggest that the entire neuraxis may be affected
      by long-term recovery from spinal trauma. CONCLUSION: These results suggest that
      diffusion tensor imaging may be useful in the assessment of SCI recovery.

PMID- 18719030
TI  - Frequency and outcome of pulmonary polymethylmethacrylate embolism during
      percutaneous vertebroplasty.
AB  - BACKGROUND AND PURPOSE: During percutaneous polymethylmethacrylate (PMMA)
      vertebroplasty (PV), PMMA cement may migrate into the venous system and
      subsequently be transported to the pulmonary arteries. Frequency, outcome, and
      imaging findings of PMMA pulmonary embolism are poorly understood. We
      retrospectively assessed the frequency and outcome of PMMA embolism during PV in
      a large patient cohort and evaluated the relationship of the volume of injected
      PMMA to the occurrence of pulmonary PMMA embolism. MATERIALS AND METHODS: Between
      2001 and 2007, 532 osteoporotic compression fractures in 299 consecutive patients
      were treated with PV. PMMA embolism was defined as venous PMMA migration toward
      the lungs visible on biplane fluoroscopy during PV. CT was performed immediately
      and 1 year after PMMA migration. RESULTS: Venous PMMA migration occurred during
      11 PVs in 11 patients (2.1%, 95% confidence interval, 1.1-3.7%). CT in 8 patients
      demonstrated small peripheral pulmonary PMMA emboli. All 11 patients remained
      asymptomatic during 1-year follow-up. Repeat CT scanning after 1 year in 6
      patients demonstrated unchanged pulmonary PMMA deposits without late reactive
      changes. Mean injected cement volume in patients with and without PMMA embolism
      was not different (3.6 +/- 1.06 mL versus 3.3 +/- 1.16 mL, P = .43). Similar
      comparison for thoracic and thoracolumbar vertebrae yielded P values of .07 and
      .9. CONCLUSION: Pulmonary PMMA embolism during PV is an infrequent complication
      without permanent clinical sequelae. After 1 year, no pulmonary reaction was seen
      on CT. No definite relationship of PMMA emboli with injected cement volume could
      be established.

PMID- 18719031
TI  - Stent management of coil herniation in embolization of internal carotid
      aneurysms.
AB  - BACKGROUND AND PURPOSE: Coil herniation into the parent artery after detachment
      is an uncommon complication of embolization of the intracranial aneurysm. We
      report our experience with stent reconstruction of the lumen and flow of the
      internal carotid artery (ICA) after coil herniation during embolization for
      intracranial ICA aneurysms and the possible mechanisms of coil herniation.
      MATERIALS AND METHODS: A series of 216 consecutive patients was treated by
      endovascular coil embolizations for intracranial aneurysms. Of these patients,
      there were 9 (4 men, 5 women; 32-68 years of age) complicating with coil
      herniation into the ICA and undergoing stent deployment to reconstruct the ICA
      lumen (n = 8) or both lumen and flow (n = 1). Wide-neck aneurysms were found in 8
      and narrow-neck, in 1. Aneurysms were in the posterior communicating artery (n =
      5) and the paraophthalmic (n = 3) and cavernous portions (n = 1) of the ICA. Self
      expandable stents were deployed in the ICA in 6; balloon-mounted stents were
      selected in 3. RESULTS: The causes of coil herniation appeared to be coil
      instability after detachment (n = 6), excessive embolization (n = 1),
      microcatheter-related problems (n = 1), or being pushed by subsequent coil
      embolization (n = 1). Endovascular stent placement to reconstruct the lumen
      and/or flow of the ICA was technically successful in all 9 patients; 1 needed a
      second stent due to further coil migration. No significant procedure-related
      complications were found. Clinical follow-up was 8-35 months. CONCLUSION: Coil
      herniation occasionally occurs during endovascular embolization of ICA aneurysms
      because of coil instability after detachment, excessive embolization,
      microcatheter-related problems, or pushing by subsequent coil embolization. In
      this small series, stent placement was safe and effective in the reconstruction
      of the arterial lumen and/or restoration of flow past a herniated coil mass.

PMID- 18719032
TI  - Endovascular treatment of large and giant aneurysms.
AB  - Very large and giant (> or =15 mm) cerebral aneurysms have a poor natural
      history, with high risk of subarachnoid hemorrhage or progressive symptoms of
      mass effect. Several endovascular techniques may be applied for treatment,
      depending on location, size, anatomy and presence of collateral circulation. The
      authors reviewed their clinical experience in endovascular treatment of 232 very
      large and giant aneurysms and present their perspective on the present state of
      the art in endovascular therapy for these aneurysms.

PMID- 18719033
TI  - Diffusion-weighted MR imaging of ameloblastomas and keratocystic odontogenic
      tumors: differentiation by apparent diffusion coefficients of cystic lesions.
AB  - BACKGROUND AND PURPOSE: Ameloblastomas and keratocystic odontogenic tumors are
      major aggressive odontogenic tumors in the maxillomandibular regions, but the
      differentiation between these 2 tumors is frequently ineffective based on only
      conventional CT and MR imaging findings. Here, we evaluated diffusion-weighted MR
      imaging for the differentiation of these 2 odontogenic tumors. MATERIALS AND
      METHODS: We prospectively studied 9 patients with ameloblastoma and 7 patients
      with keratocystic odontogenic tumor using diffusion-weighted MR imaging. Apparent
      diffusion coefficients (ADCs) of the nonenhancing and solid lesions in these
      tumors were determined with use of 2 b factors (500 and 1000). RESULTS: Two types
      of nonenhancing lesions were identified; one with high signal intensity on fat
      suppressed T2-weighted images (type A) and the other with low or intermediate
      intensity (type B). The type A nonenhancing lesions were observed in all the
      ameloblastomas, but they were evident in only 2 keratocystic odontogenic tumors.
      It is interesting to note that the ADCs of the nonenhancing lesions in the
      ameloblastomas were significantly higher than those of the nonenhancing lesions
      in the keratocystic odontogenic tumors (2.48 +/- 0.20 x 10(-3) mm(2)/s vs 1.13 +/
      0.56 x 10(-3) mm(2)/s; P < .001). The ADCs of the solid lesions in the
      ameloblastomas (1.39 +/- 0.15 x 10(-3) mm(2)/s) were significantly lower than
      those of the nonenhancing lesions in the ameloblastomas and were similar to those
      of the nonenhancing lesions in the keratocystic odontogenic tumors. CONCLUSION:
      ADC determination may be used as an adjunct tool for differentiation between
      ameloblastomas and keratocystic odontogenic tumors.

PMID- 18719034
TI  - Predictors and timing of hypotension and bradycardia after carotid artery
      stenting.
AB  - BACKGROUND AND PURPOSE: Hypotension and bradycardia are common in carotid artery
      stenting (CAS) and are particularly worrisome in the high risk patient who is
      typically referred for CAS. The purpose of this work was to assess the incidence
      and predictors of hypotension and bradycardia and the risk of their delayed
      occurrence after CAS. MATERIALS AND METHODS: A total of 53 men and 40 women
      (median age, 71 years) with symptomatic (57%) or asymptomatic (42%) carotid
      artery stenosis had CAS performed in our institution between December 2002 and
      January 2007. Patient vital sign records for the 12 hours post-CAS were analyzed.
      The relative decrease of blood pressure and pulse rate were used as primary end
      points, and the requirement of pressor or anticholinergic drugs was used as a
      surrogate end point. Significant predictors of hypotension and bradycardia were
      analyzed with a logistic regression model. Cumulative freedom from hypotension
      and bradycardia was calculated by using the Kaplan-Meier method. Negative
      predictive value (NPV) of screening for early hypotension and bradycardia was
      determined. RESULTS: The incidence of hypotension, bradycardia, and both was 14%,
      23%, and 15%, respectively. Drug intervention was required in 45 patients (48%).
      Asymptomatic stenosis was an independent predictor of hypotension and
      bradycardia. Stenosis proximity to the bifurcation and dilation percentage were
      independent predictors of the drug intervention requirement. Seven patients (8%)
      had new onset of hypotension or bradycardia later than 6 hours post-CAS. The NPV
      of early hypotension and bradycardia was 97% and 93%, respectively. CONCLUSION:
      In this retrospective study, the risk of hypotension or bradycardia after CAS is
      significantly influenced by the degree of dilation performed, and the risk of
      their delayed occurrence may justify a minimum of 12 hours postprocedural vital
      sign monitoring.

PMID- 18719035
TI  - Renal safety of CT angiography and perfusion imaging in the emergency evaluation
      of acute stroke.
AB  - BACKGROUND AND PURPOSE: Multimodal CT imaging with contrast-enhanced CT
      angiography (CTA) and CT perfusion (CTP) is increasingly being used to guide
      emergency management of acute stroke. However, little has been reported about the
      safety of intravenous contrast administration associated with these studies in
      the acute stroke population, including cases in which baseline creatinine values
      are unknown. We investigated the incidence of contrast-induced nephropathy (CIN),
      defined as a 25% or more increase in baseline creatinine levels within 72 hours
      of contrast administration and chronic kidney disease in patients receiving CTA+/
      CTP at our regional stroke center. MATERIALS AND METHODS: We analyzed 198
      patients who underwent contrast CT studies for evaluation of acute ischemic or
      hemorrhagic stroke at our center (2003-2007). Through retrospective chart
      abstraction, we analyzed serial creatinine levels (baseline to day 3) and later
      values (>/=day 4) where available. The incidences of CIN and/or chronic kidney
      disease were documented. After power analysis, CIN and non-CIN groups were
      compared by using the unpaired t test, Wilcoxon rank sum test, or Fisher exact
      test. RESULTS: None of the 198 patients developed chronic kidney disease or
      required dialysis. Of 175 patients with serial creatinine measurements between
      baseline and day 3, 5 (2.9%) developed CIN. The incidence of CIN was 2% in
      patients who were scanned before a baseline creatinine level was available.
      CONCLUSION: The incidence of renal sequelae is relatively low in acute stroke
      patients undergoing emergent multimodal CT scanning. Prompt CTA/CTP imaging of
      acute stroke, if indicated, need not be delayed in those with no history of renal
      impairment.

PMID- 18719036
TI  - Preoperative grading of presumptive low-grade astrocytomas on MR imaging:
      diagnostic value of minimum apparent diffusion coefficient.
AB  - BACKGROUND AND PURPOSE: Histopathologic grade of glial tumors is inversely
      correlated with the minimum apparent diffusion coefficient (ADC). We assessed the
      diagnostic values of minimum ADC for preoperative grading of supratentorial
      astrocytomas that were diagnosed as low-grade astrocytomas on conventional MR
      imaging. MATERIALS AND METHODS: Among 118 patients with astrocytomas (WHO grades
      II-IV), 16 who showed typical MR imaging findings of low-grade supratentorial
      astrocytomas on conventional MR imaging were included. All 16 patients underwent
      preoperative MR imaging and diffusion-weighted imaging. The minimum ADC value of
      each tumor was determined from several regions of interest in the tumor on ADC
      maps. To assess the relationship between the minimum ADC and tumor grade, we
      performed the Mann-Whitney U test. A receiver operating characteristic (ROC)
      analysis was used to determine the cutoff value of the minimum ADC that had the
      best combination of sensitivity and specificity for distinguishing low- and high
      grade astrocytomas. RESULTS: Eight of the 16 patients (50%) were confirmed as
      having high-grade astrocytomas (WHO grades III and IV), and the other 8 patients
      were confirmed as having low-grade astrocytomas (WHO grade II). The median
      minimum ADC of the high-grade astrocytoma (1.035 x 10(-3) mm(2) . sec(-1)) group
      was significantly lower than that of the low-grade astrocytoma group (1.19 x 10(
      3) mm(2) . sec(-1)) (P = .021). According to the ROC analysis, the cutoff value
      of 1.055 x 10(-3) mm(2) . sec(-1) for the minimum ADC generated the best
      combination of sensitivity (87.5%) and specificity (79%) (P = .021). CONCLUSION:
      Measuring minimum ADC can provide valuable diagnostic information for the
      preoperative grading of presumptive low-grade supratentorial astrocytomas.

PMID- 18719037
TI  - Dose measurement on both patients and operators during neurointerventional
      procedures using photoluminescence glass dosimeters.
AB  - BACKGROUND AND PURPOSE: Although radiation skin injuries associated with
      interventional radiology have been known as a critical issue, there are few
      reports mentioning direct measurement of the entrance skin dose (ESD). Thus, the
      purpose of this study was to clarify the regional distributions of ESDs in
      neurointervention. MATERIALS AND METHODS: Using photoluminescence glass
      dosimeters (PLDs), we measured the ESDs in 32 patients with a median age of 61.5
      years. Angiographic parameters, including exposure time, dose-area product (DAP),
      and the number of digital subtraction angiography (DSA) studies and frames, were
      recorded. The ESDs of operators were analyzed by the same method. RESULTS: The
      maximum ESD of 28 therapeutic procedures was 1.8 +/- 1.3 Gy. Although the
      averaged ESD on the right temporo-occipital region was higher than that in other
      regions, disease-specific patterns were not observed. Statistically positive
      correlations were found between the maximum ESD and exposure time (r = 0.5283, P
      = .005), DAP (r = 0.7917, P < .001), the number of DSA studies (r = 0.5636, P =
      .002), and the number of DSA frames (r = 0.8583, P < .001). As for operators,
      ESDs to the left upper extremity were significantly higher than those to other
      regions. However, most of the ESDs were <0.2 mGy. Lead protective garments
      reduced the exposure doses to approximately one half to one tenth. CONCLUSION: It
      was shown that the regional ESD could be measured by applying the PLD. This
      method should contribute to reducing the dose accumulation in patients as well as
      in operators.

PMID- 18719038
TI  - Delayed migration of a self-expanding intracranial microstent.
AB  - A 43-year-old patient with a basilar apex aneurysm had a 4.5-mm x 14-mm
      Enterprise stent placed from the midbasilar artery to the left P1 segment of the
      posterior cerebral artery. The patient experienced vertigo 4 months after stent
      placement and 1 week after stopping clopidogrel. At 5 months postembolization,
      angiography showed stent migration into the proximal basilar artery. This is the
      first described case of the spontaneous delayed migration of a self-expanding
      intracranial microstent.

PMID- 18719039
TI  - Safety and efficacy of adjunctive balloon remodeling during endovascular
      treatment of intracranial aneurysms: a literature review.
AB  - BACKGROUND AND PURPOSE: Concurrent temporary inflation of a nondetachable balloon
      in the parent artery has been reported to be useful during endovascular coiling
      of complex, wide-neck aneurysms, facilitating truer coil reconstruction of the
      native vessel. Nevertheless, there exists concern that adjunctive use of balloon
      assistance may lead to increased adverse events during aneurysm coiling.
      MATERIALS AND METHODS: A literature search of all of the unassisted and balloon
      remodeling studies published between 1997 and 2006 was conducted with application
      of strict selection criteria based on the reporting of complication incidence and
      outcome. The final cohort was analyzed to determine rates and clinical outcomes
      of iatrogenic aneurysm rupture and thromboembolism. Additional data were
      collected on the degree of initial and follow-up aneurysm occlusion rates.
      RESULTS: A total of 83 potential studies (4973 patients) were identified, from
      which 23 articles reporting results for 867 traditional-unassisted and 273
      balloon-assisted coiled aneurysms met inclusion criteria for the analysis of
      thromboembolic complications, and 21 articles with 993 routinely coiled and 170
      balloon-remodeled aneurysms were eligible for iatrogenic perforation analysis. No
      statistically significant difference was found in the rates of thromboembolism.
      Iatrogenic perforation rates were also comparable, though the overall numbers
      were too few for meaningful statistical analysis. Both initial and follow-up
      aneurysm occlusion rates were higher in balloon-assisted cases. CONCLUSION: This
      largest-to-date literature review and meta-analysis did not demonstrate a higher
      incidence of thromboembolic events or iatrogenic rupture with the use of
      adjunctive balloon remodeling compared with unassisted coiling. Balloon
      remodeling appears to result in higher initial and follow-up aneurysm occlusion
      rates.

PMID- 18719041
TI  - Patient factors associated with receipt of combination antipsychotic drug therapy
      in the treatment of schizophrenia.
AB  - Although discouraged in available treatment guidelines, combination antipsychotic
      prescribing (CAP) is a common practice in the treatment of schizophrenia. Patient
      characteristics may be associated with this type of treatment. A dataset (N =
      363) derived from parallel randomised controlled trials was interrogated to
      identify factors associated with the receipt of CAP, and a logistic regression
      analysis was used to predict the occurrence of CAP. Significant predictors of CAP
      were longer illness, low global functioning score and high treatment adherence
      rating. Co-prescribed patients received a higher combined dose.

PMID- 18719042
TI  - Retracted. The biphasic changes of insulin secretion in schizophrenic patients
      treated with olanzapine.

PMID- 18719043
TI  - Lamotrigine-induced obsessional symptoms in a patient with bipolar II disorder: a
      case report.
AB  - Lamotrigine is an anticonvulsant that appears to have a mainly antidepressant
      effect and is indicated for the maintenance treatment of bipolar depression.
      Literature associated with obsessional symptoms related to lamotrigine treatment
      is limited. We report the emergence of obsessive symptoms during treatment with
      lamotrigine in a patient who subsequently experienced significant improvement
      after dose reduction and stopping of this medication. The obsessive symptoms
      associated with lamotrigine treatment were observed after the lamotrigine dose
      was increased to 100 mg/day. The possible mechanisms, including inhibition on the
      presynaptic release of glutamate and alteration of striatal dopamine uptake, are
      discussed. It is unclear why lamotrigine induces obsessions in some patients.
      Controlled studies are necessary to identify the population at risk for
      obsessionality in bipolar illness following treatment with lamotrigine and to
      investigate a possible dose-response relationship between obsessive symptoms and
      lamotrigine.

PMID- 18719044
TI  - Electrophysiological effects of the co-administration of escitalopram and
      bupropion on rat serotonin and norepinephrine neurons.
AB  - Clinical studies indicate that addition of bupropion to selective serotonin (5
      HT) reuptake inhibitors (SSRIs) provides incremental benefit over SSRI
      monotherapy in depression. This study was designed to investigate the effects of
      co-administration of bupropion with escitalopram on the firing rate of 5-HT and
      norepinephrine (NE) neurons in anesthetized rats. Escitalopram (10 mg/kg/day x 2
      days), given via subcutaneously (s.c.) implanted minipumps, decreased the firing
      of 5-HT and NE neurons by 70% and 55%, respectively. The firing of 5-HT neurons,
      unlike that of NE neurons, recovered after the 14-day escitalopram regimen.
      Bupropion, injected once daily (30 mg/kg/day, s.c. x 2 days), did not increase 5
      HT firing but decreased that of NE by 55%. After 14 days of repeated bupropion
      administration, 5-HT firing was increased by 50%, and NE firing was back to
      baseline. Co-administration of escitalopram and bupropion doubled 5-HT firing
      after 2 and 14 days, whereas NE neurons were inhibited by 60% after 2 days, but
      partially recovered after 14 days. The responsiveness of 5-HT(1A) autoreceptors
      was significantly attenuated in the combination-treated rats after 2 days,
      indicating an early desensitization. These results provide support for
      contributions from 5-HT and NE mechanisms for enhanced effectiveness of
      combination of SSRI and bupropion treatment.

PMID- 18719045
TI  - Neurocognitive performance during acute THC intoxication in heavy and occasional
      cannabis users.
AB  - Performance impairment during Delta(9)-tetrahydrocannabinol (THC) intoxication
      has been well described in occasional cannabis users. It is less clear whether
      tolerance develops to the impairing effects of THC in heavy users of cannabis.
      The aim of the present study was to assess neurocognitive performance during
      acute THC intoxication in occasional and heavy users. Twenty-four subjects (12
      occasional cannabis users and 12 heavy cannabis users) participated in a double
      blind, placebo-controlled, two-way mixed model design. Both groups received
      single doses of THC placebo and 500 microg/kg THC by smoking. Performance tests
      were conducted at regular intervals between 0 and 8 h after smoking, and included
      measures of perceptual motor control (critical tracking task), dual task
      processing (divided attention task), motor inhibition (stop signal task) and
      cognition (Tower of London). THC significantly impaired performance of occasional
      cannabis users on critical tracking, divided attention and the stop signal task.
      THC did not affect the performance of heavy cannabis users except in the stop
      signal task, i.e. stop reaction time increased, particularly at high THC
      concentrations. Group comparisons of overall performance in occasional and heavy
      users did not reveal any persistent performance differences due to residual THC
      in heavy users. These data indicate that cannabis use history strongly determines
      the behavioural response to single doses of THC.

PMID- 18719046
TI  - 'Let's not give in to Descartes: we need pharmacology and psychotherapy'.

PMID- 18719047
TI  - Efficacy and tolerability of duloxetine in the treatment of patients with
      borderline personality disorder: a pilot study.
AB  - Guidelines of the American Psychiatric Association for borderline personality
      disorder (BPD) indicate selective serotonin reuptake inhibitors and the serotonin
      and noradrenaline reuptake inhibitor (SNRI) venlafaxine for treating affective
      dysregulation and impulsive behavioural dyscontrol symptoms. The SNRI duloxetine
      has been studied in patients with major depression, generalized anxiety disorder
      and fibromyalgia, showing particular efficacy on somatic complaints. This study
      investigates duloxetine in the treatment of patients with BPD. Eighteen
      outpatients with a DSM-IV-TR diagnosis of BPD were treated with open-label
      duloxetine, 60 mg/day, for 12 weeks. Patients were assessed at baseline, week 4
      and 12 with the CGI Severity item, the BPRS, the HAM-D, the HAM-A, the SOFAS, the
      BPD Severity Index (BPDSI) and the HSCL-90-Somatization Subscale (HSCL-90 SOM).
      Adverse effects were evaluated using the Dosage Record Treatment Emergent Symptom
      Scale. Statistics were performed with the analysis of variance. Significant P
      values were <or=0.05. Fourteen patients completed the study. Four patients
      (22.2%) discontinued treatment in the first 4 weeks because of non-compliance. A
      significant change was found for: BPRS, HAM-D, SOFAS, BPDSI total score and items
      'impulsivity', 'outbursts of anger' and 'affective instability' and HSCL-90 SOM.
      Adverse effects were mild headache and nausea. Initial results suggest that
      duloxetine is an effective and well-tolerated treatment for BPD, with positive
      effects on somatic symptoms.

PMID- 18719048
TI  - Enhanced tolerability of the 5-hydroxytryptophane challenge test combined with
      granisetron.
AB  - A recently developed oral serotonergic challenge test consisting of 5
      Hydroxytryptophane (5-HTP, 200 mg) combined with carbidopa (CBD, 100 mg + 50 mg)
      exhibited dose-related neuroendocrine responsiveness and predictable
      pharmacokinetics. However, its applicability is limited by nausea and vomiting. A
      randomized, double-blind, placebo-controlled, four-way crossover trial was
      performed in 12 healthy male volunteers. The 5-HTP/CBD-challenge was combined
      with two oral anti-emetics (granisetron, 2 mg or domperidone, 10 mg) to
      investigate its reliability when side-effects are suppressed. The neuroendocrine
      response (serum cortisol and prolactin), the side-effect profile [Visual Analogue
      Scale Nausea (VAS)] and vomiting subjects per treatment were the main outcome
      measures. Compared to 5-HTP/CBD/placebo, 5-HTP/CBD/ granisetron had no impact on
      cortisol [% change with 95% confidence interval: -7.1% (18.9; 6.5)] or prolactin
      levels [-9.6% (-25.1; 9.1)]; 5-HTP/CBD/domperidone increased cortisol [+13.0% (
      4.2; 33.4)], and increased prolactin extensively [+336.8% (245.7; 451.9)].
      Compared to placebo, VAS Nausea increased non-significantly with granisetron
      [+7.6 mm (-1.3; 16.5)], as opposed to domperidone [+16.2 mm (7.2; 25.2)] and 5
      HTP/CBD/placebo [+14.7 mm (5.5; 23.8)]. No subjects vomited with granisetron,
      compared to two subjects treated with 5-HTP/CBD/placebo and five subjects with
      domperidone. Compared with 5-HTP/CBD/placebo, granisetron addition decreased
      C(max) of 5-HTP statistically significantly different (from 1483 to 1272 ng/ml)
      without influencing AUC(0- infinity). Addition of granisetron to the combined 5
      HTP/CBD challenge suppresses nausea and vomiting without influencing the
      neuroendocrine response or pharmacokinetics, enhancing its clinical applicability
      in future psychiatric research and drug development.

PMID- 18719049
TI  - Asenapine induces differential regional effects on serotonin receptor subtypes.
AB  - Asenapine, a novel psychopharmacologic agent being developed for the treatment of
      schizophrenia and bipolar disorder, has high affinity for a wide range of
      receptors, including the serotonergic receptors 5-HT(1A), 5-HT(1B), 5-HT(2A), 5
      HT( 2B), 5-HT(2C), 5-HT(5A), 5-HT(6) and 5-HT( 7). We examined the long-term
      effects in rat brain of multiple doses of asenapine on representative serotonin
      receptor subtypes: 5-HT(1A), 5-HT(2A) and 5-HT(2C). Rats were given asenapine
      (0.03, 0.1 or 0.3 mg/kg) subcutaneously twice daily or vehicle for 4 weeks. Brain
      sections were collected from the medial prefrontal cortex (mPFC), dorsolateral
      frontal cortex (DFC), caudate putamen, nucleus accumbens, hippocampal CA( 1) and
      CA(3) regions, and entorhinal cortex and processed for in-vitro receptor
      autoradiography. Asenapine 0.1 and 0.3 mg/kg significantly increased 5-HT(1A)
      binding in mPFC (by 24% and 33%, respectively), DFC (27%, 31%) and hippocampal
      CA(1) region (23%, 25%) (all P < 0.05). All three asenapine doses (0.03, 0.1 and
      0.3 mg/kg) significantly decreased 5-HT(2A) binding by a similar degree in mPFC
      (40%, 44%, 47%, respectively) and DFC (45%, 51%, 52%) (all P < 0.05), but did not
      alter 5-HT(2A) binding in the other brain regions studied. In contrast to the
      effects on 5-HT(1A) and 5-HT(2A) receptors, asenapine did not alter 5-HT(2C)
      binding in any brain region examined at the doses tested. Our results indicate
      that repeated administration of asenapine produces regional-specific effects on 5
      HT(1A) and 5-HT(2A) receptors in rat forebrain regions, which may contribute to
      the distinctive psychopharmacologic profile of asenapine.

PMID- 18719050
TI  - Estrogen treatment up-regulates female genes but does not suppress all early
      testicular markers during rainbow trout male-to-female gonadal
      transdifferentiation.
AB  - In non-mammalian vertebrates, estrogens are key players in ovarian
      differentiation, but the mechanisms by which they act remain poorly understood.
      The present study on rainbow trout was designed to investigate whether estrogens
      trigger the female pathway by activating a group of early female genes (i.e.
      cyp19a1, foxl2a, foxl2b, fst, bmp4, and fshb) and by repressing early testicular
      markers (i.e. dmrt1, nr0b1, sox9a1 and sox9a2). Feminization was induced in
      genetically all-male populations using 17alpha-ethynylestradiol (EE2, 20 mg/kg of
      food during 2 months). The expression profiles of 100 candidate genes were
      obtained by real-time RT-PCR and 45 expression profiles displayed a significant
      differential expression between control populations (males and females) and EE2
      treated populations. These expression profiles were grouped in five temporally
      correlated expression clusters. The estrogen treatment induced most of the early
      ovarian differentiation genes (foxl2a, foxl2b, fst, bmp4, and fshb) and in
      particular foxl2a, which was strongly and quickly up-regulated. Simultaneously,
      Leydig cell genes, involved in androgen synthesis, as well as some Sertoli cell
      markers (amh, sox9a2) were strongly repressed. However, in contrast to our
      initial hypothesis, some genes considered as essential for mammalian and fish
      testis differentiation were not suppressed during the early process of estrogen
      induced feminization (dmrt1, nr0b1, sox9a1 and pax2a) and some were even strongly
      up-regulated (nr0b1, sox9a1and pax2a). In conclusion, estrogens trigger male-to
      female transdifferentiation by up-regulating most ovarian specific genes and this
      up-regulation appears to be crucial for an effective feminization, but estrogens
      do not concomitantly down-regulate all the testicular differentiation markers.

PMID- 18719051
TI  - A comparison of the reproducibility of manual tracing and on-screen digitization
      for cephalometric profile variables.
AB  - The aim of this investigation was to analyse and compare the reproducibility of
      manual cephalometric tracings with on-screen digitization using a soft tissue
      analysis. A random sample of 20 lateral cephalometric radiographs, in the natural
      head posture, was selected. On-screen digitization using Viewbox 3.1.1.9
      cephalometric software and manual tracing on a 1:1 printout of the image was
      carried out twice in different sessions 1 week apart. Differences were analysed
      using a repeated measurement analysis of variance with method, session, and
      method-session interaction as explaining variables. The differences were
      expressed as an absolute percentage of the overall mean. The findings of the
      present study indicate that the two measurement methods differ significantly for
      11 variables (P = 0.001 to P = 0.042). The area around stomion was the least
      reproducible. Except for s-n(s)-unt, nasal protrusion, with the manual technique,
      all mean differences between sessions and between methods were less than 1 degree
      or 1 mm and were, on-screen, smaller for 13 variables compared with those traced
      manually. Absolute percentage differences of the overall mean were smaller for
      seven variables with the digital technique and three variables in the manual
      technique, while four manual variables and one on-screen variable exceeded 2 per
      cent of the overall mean. Although small significant differences were found, the
      clinical relevance remains questionable.

PMID- 18719052
TI  - Sleep and the epidemic of obesity in children and adults.
AB  - Sleep is an important modulator of neuroendocrine function and glucose metabolism
      in children as well as in adults. In recent years, sleep curtailment has become a
      hallmark of modern society with both children and adults having shorter bedtimes
      than a few decades ago. This trend for shorter sleep duration has developed over
      the same time period as the dramatic increase in the prevalence of obesity. There
      is rapidly accumulating evidence from both laboratory and epidemiological studies
      to indicate that chronic partial sleep loss may increase the risk of obesity and
      weight gain. The present article reviews laboratory evidence indicating that
      sleep curtailment in young adults results in a constellation of metabolic and
      endocrine alterations, including decreased glucose tolerance, decreased insulin
      sensitivity, elevated sympathovagal balance, increased evening concentrations of
      cortisol, increased levels of ghrelin, decreased levels of leptin, and increased
      hunger and appetite. We also review cross-sectional epidemiological studies
      associating short sleep with increased body mass index and prospective
      epidemiological studies that have shown an increased risk of weight gain and
      obesity in children and young adults who are short sleepers. Altogether, the
      evidence points to a possible role of decreased sleep duration in the current
      epidemic of obesity.

PMID- 18719053
TI  - Elevated free IGF2 levels in localized, early-stage breast cancer in women.
AB  - OBJECTIVE: Epidemiological studies imply an association between circulating IGF1
      and breast cancer, whereas the role of IGF2, which also acts on the IGF1
      receptor, is less settled. This study investigates the association between IGF2
      and breast cancer in patients with localized disease. DESIGN: The participants
      were women with well-characterized, early stage, localized breast cancer (n=43)
      and matched healthy women (n=38), from whom fasting serum levels of IGF-related
      peptides were measured. RESULTS: In patients, mean free IGF2 was increased (+57%,
      P<0.001), in spite of reduced total IGF2 levels (-12%, P=0.003) when compared
      with controls. Similar changes were seen in free IGF1 (+28%, P=0.004) and total
      IGF1 (-16% P=NS). Pro-IGF2 and IGF-binding protein 1 (IGFBP1) were unchanged.
      IGFBP2 was reduced by 22% in the patients (P=0.004). The patients showed reduced
      IGFBP3 protease activity and accordingly increased levels of intact IGFBP3,
      whereas total IGFBP3 was unchanged. CONCLUSION: Women with localized, early-stage
      breast cancer show elevated circulating free IGF1 and IGF2, reduced total IGF2
      and alterations in IGFBPs. The changes observed despite minimal cancer disease
      suggest a role for the circulating IGF system in the progression of breast cancer
      in women.

PMID- 18719054
TI  - Occupational history quality in patients with newly documented, clinician
      diagnosed chronic bronchitis.
AB  - BACKGROUND: Approximately 15% of cases of COPD, including chronic bronchitis, is
      attributable to occupational exposures. An occupational history is essential to
      identify exposures responsible for work-related chronic bronchitis. METHODS: We
      conducted a structured retrospective analysis of the medical records of veterans,
      18 to 70 years of age, newly diagnosed with chronic bronchitis in order to
      achieve the following: (1) to assess the quality of documented occupational
      histories; and (2) to characterize the management of patients with a history of
      exposure to a potentially hazardous respiratory substance. We also analyzed
      occupational exposure data reported by patients on a structured questionnaire.
      RESULTS: Sixty patients were included in the final analysis. A total of 6,150
      notes were reviewed. Occupational status was documented in the records of 54
      patients (90%). A description of occupational duties was recorded in 32 records
      (53%), and work exposure data in 26 records (43%). Clinicians concluded that
      occupational exposures potentially contributed to chronic bronchitis in three
      patients (5%). A recommendation for exposure avoidance was documented for six
      patients (10%). On the questionnaire, most patients reported a history of
      occupational exposure to respirable substances and symptoms of cough and/or
      shortness of breath. CONCLUSIONS: Details about job duties and occupational
      respiratory exposures were documented in the records of approximately half of
      patients with newly diagnosed chronic bronchitis. Patient self-reports of
      occupational exposures and respiratory symptoms were common. A determination that
      occupational exposures contributed to chronic bronchitis was rare. Few patients
      were counseled to take measures to avoid occupational exposures. Work-related
      chronic bronchitis may be incompletely assessed and undermanaged by clinicians.

PMID- 18719055
TI  - The asthma/mental health nexus in a population-based sample of the United States.
AB  - BACKGROUND: Asthma is one of the most prevalent chronic medical conditions in the
      United States. The relationship of asthma with psychological factors has been
      known for centuries, and recently there has been a resurgence of interest in this
      topic. This study investigates the relationship between current asthma and poor
      mental health in a nationally representative sample of the US population.
      METHODS: This study utilizes data from the 2006 Behavioral Risk Factor
      Surveillance System survey (n = 355,710). A multinomial logistic regression model
      was constructed to assess the relationship between current asthma and poor mental
      health. The relationship between formerly having asthma and poor mental health
      was also investigated. RESULTS: Persons reporting poor mental health have
      increased risk of currently having asthma compared to persons reporting good
      mental health. Additionally, this asthma/mental health relationship has a "dose
      response" relationship. For every incremental increase in days of poor mental
      health, there is a corresponding increase in risk of currently having asthma.
      Previously reported risk factors for asthma (ie, age, gender, race, marital,
      smoking, overall health, exercise, obesity, and socioeconomic status) were all
      found to be important covariates of asthma. The relationship between former
      asthma and poor mental health is less clear. CONCLUSIONS: This large, nationally
      representative sample confirms the relationship between asthma and mental health
      symptoms. Any degree of poor mental health appears to increase one's risk for
      asthma. Future research is needed to determine the causal and/or physiologic
      relationship between asthma and mental health symptoms.

PMID- 18719056
TI  - Hemodynamics and epoprostenol use are associated with thrombocytopenia in
      pulmonary arterial hypertension.
AB  - BACKGROUND: Thrombocytopenia develops in some patients with advanced pulmonary
      arterial hypertension (PAH) while receiving IV epoprostenol therapy. In this
      study, we evaluate whether epoprostenol use, other PAH medication use,
      hemodynamics, or PAH etiology are associated with thrombocytopenia in PAH.
      METHODS: Platelet counts were evaluated in 47 PAH patients receiving IV
      epoprostenol, and in 44 patients with an inadequate response to initial therapy
      with oral agents in a cross-sectional study. Associations between
      thrombocytopenia (platelet count < 150,000/mL) and epoprostenol use,
      hemodynamics, PAH etiology, and use of other PAH medications were evaluated in
      univariable and multivariable analyses. RESULTS: PAH subtypes included idiopathic
      (69%), fenfluramine (18%), connective tissue disease (10%), and congenital heart
      disease (2%)-associated PAH. Thrombocytopenia was observed in 34% of patients
      treated with epoprostenol, compared with 15% of patients receiving oral therapy
      (odds ratio [OR], 2.9; p < 0.05), and the association between epoprostenol and
      thrombocytopenia remained significant after adjustment for differences in
      hemodynamics (OR, 5.0; p < 0.05). Right atrial pressure (OR, 1.12 per mm Hg; p <
      0.05) and mixed venous oxygen saturation (Svo(2)) [OR, 0.92 per percentage; p <
      0.05] were also associated with thrombocytopenia in univariable analyses; after
      logistic regression analysis, both the use of epoprostenol and Svo(2) were
      independently associated with thrombocytopenia. In a separate analysis including
      only patients with current or prior epoprostenol use, epoprostenol dose and right
      atrial pressure were inversely associated with platelet count. CONCLUSION:
      Epoprostenol use and severity of hemodynamic abnormalities are associated with
      thrombocytopenia in PAH, and these effects appear to be independent and additive.

PMID- 18719057
TI  - Pulmonary pressure and cardiac function in chronic mountain sickness patients.
AB  - BACKGROUND: Chronic mountain sickness (CMS) is characterized by a loss of
      adaptation to hypoxia in high-altitude (HA) dwellers. Chronic hypoxemia,
      excessive erythrocytosis and frequently pulmonary hypertension (PH), which may
      lead to cardiac failure, develop in patients. We sought to assess the
      determinants of cardiac function in CMS patients with hypoxia-induced PH.
      METHODS: Fifteen healthy men living at sea level (SL) were compared to 15 healthy
      men living at HA and 55 patients with CMS from Cerro de Pasco, Peru (altitude,
      4,300 m). Pulmonary pressures and cardiac function were estimated by
      echocardiography. RESULTS: None of the subjects had overt cardiac failure
      symptoms. CMS patients exhibited elevated mean pulmonary pressures as assessed by
      high-tricuspid pressure gradients (CMS patients, 34 +/- 10 mm Hg; HA subjects, 25
      +/- 4 mm Hg [p = 0.002]; and SL subjects, 19 +/- 3 mm Hg [p < 0.001]). They also
      showed right ventricular (RV) dilation (mean end-diastolic RV area: CMS patients,
      17 +/- 2 cm(2); HA subjects, 13 +/- 2 cm(2); SL subjects, 12 +/- 2 cm(2); p <
      0.001) but did not display impaired systolic ventricular function. However, the
      RV Tei index was increased in CMS and HA subjects (CMS patients, 0.56 +/- 0.15;
      HA subjects, 0.52 +/- 0.12; SL subjects, 0.21 +/- 0.12; p < 0.001). CONCLUSION:
      Despite obvious pulmonary arterial hypertension and right heart dilation, CMS
      patients did not show any symptom or echocardiographic parameter of heart
      failure. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT00424970.

PMID- 18719058
TI  - Survival for patients With HIV admitted to the ICU continues to improve in the
      current era of combination antiretroviral therapy.
AB  - BACKGROUND: The combination antiretroviral therapy (ART) era (1996 to the
      present) has been associated with improved survival among HIV-infected
      outpatients, but ICU data from 2000 to the present are limited. METHODS: We
      conducted a retrospective study of HIV-infected adults who had been admitted to
      the ICU at San Francisco General Hospital (from 2000 to 2004). The primary
      outcome was survival to hospital discharge. RESULTS: During the 5-year study
      period, there were 311 ICU admissions for 281 patients. Respiratory failure
      remained the most common indication for ICU admission (42% overall), but the
      proportion of patients with respiratory failure decreased each year from 52 to
      34% (p = 0.02). Hospital survival ratios significantly increased during the 5
      year period (p = 0.001). ART use at ICU admission was not associated with
      survival, but it was associated with higher CD4 cell counts, lower plasma HIV RNA
      levels, higher serum albumin levels, and lower proportions with AIDS-associated
      ICU admission diagnoses and with Pneumocystis pneumonia. In a multivariate
      analysis, a higher serum albumin level (adjusted odds ratio [AOR], 2.08; 95%
      confidence interval [CI], 1.41 to 3.06; p = 0.002) and the absence of mechanical
      ventilation (AOR, 6.11; 95% CI, 2.73 to 13.72; p < 0.001) were associated with
      survival. CONCLUSIONS: In this sixth in a series of consecutive studies started
      in 1981, we found that the epidemiology of ICU admission diagnoses continues to
      change. Our study also found that survival for critically ill HIV-infected
      patients continues to improve in the current era of ART. Although ART use was not
      associated with survival, it was associated with predictors that were associated
      with survival in a multivariate analysis.

PMID- 18719059
TI  - Effects of aminoguanidine, an inhibitor of inducible nitric oxide synthase, on
      nitric oxide production and its metabolites in healthy control subjects, healthy
      smokers, and COPD patients.
AB  - BACKGROUND: Nitric oxide (NO) is produced by resident and inflammatory cells in
      the respiratory tract by the enzyme NO synthase (NOS), which exists in three
      isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS. NO
      production is increased in patients with COPD, and the production of NO under
      oxidative stress conditions generates reactive nitrogen species that may amplify
      the inflammatory response in COPD. METHODS: To examine the role of increased NO
      in COPD, we administered a relatively selective iNOS inhibitor, aminoguanidine,
      by nebulization in a double-blind, placebo-controlled study in COPD patients,
      healthy smokers, and healthy nonsmoking subjects. We investigated whether
      aminoguanidine had any effect on exhaled NO produced in the central lung (flux of
      NO from the airways [Jno] and peripheral lungs (concentration of NO in peripheral
      lung [Calv], on NO metabolites (nitrite [NO(2)(-)]/nitrate [NO(3)(-)],
      peroxinitrite [ONOO(-)], nitrotyrosine), and on a marker of oxidative stress (8
      isoprostane) in exhaled breath condensate (EBC) and in sputum. RESULTS:
      Aminoguanidine administration resulted in a significant reduction in Jno compared
      with administration of the saline solution control in healthy subjects, smokers,
      and COPD patients. Calv in smokers and in COPD patients was not completely
      inhibited 1 h after aminoguanidine inhalation, in marked contrast to previous
      results in asthma. Moreover, ONOO(-) and NO(2)(-)/NO(3)(-) levels were also
      increased in EBC and in sputum of smokers and COPD and were not completely
      inhibited following aminoguanidine inhalation. 8-Isoprostane levels were also
      increased in smokers and in COPD patients but were not reduced after
      aminoguanidine inhalation. CONCLUSIONS: These results suggest that the
      constitutive NOS isoform as well as iNOS might be involved in NO release and
      contribute to the high Calv and ONOO(-) production in patients with COPD. TRIAL
      REGISTRATION: Clinicaltrials.gov Identifier: NCT00180635.

PMID- 18719060
TI  - Cost-benefit analysis of a simulated institution-based preoperative smoking
      cessation intervention in patients undergoing total hip and knee arthroplasties
      in France.
AB  - BACKGROUND: The literature on preoperative smoking cessation indicates that
      smoking patients are more likely to have postoperative complications. However,
      the economic implications of such complications are unclear. In particular, the
      balance between the cost of a preoperative intervention for smoking cessation
      (PISC) and the benefit resulting from the potential decrease in hospitalization
      costs is not known. METHODS: Only one previous study, a randomized trial
      involving smokers scheduled for hip or knee replacement surgery, provides
      sufficient data to simulate the hospital course of patients subjected or not
      subjected to a PISC. We used a multistate Markov-type model and official French
      hospital costs for 2008 to simulate this situation. The cost-benefit analysis
      adopted the payer's perspective. RESULTS: The mean benefit, corresponding to the
      decrease in the cost of the hospital stay for a reference case patient having
      followed a PISC, was estimated at 313 euros, with a corresponding mean cost of
      the PISC estimated at 196 euros. Therefore, the PISC was associated with a cost
      saving of 117 euros per patient. The results were most sensitive to the cost of
      ICU care as a proxy for cost of smoking-related complications, and to the
      relative risk of complication between patients with and without a PISC.
      CONCLUSION: Under the conditions simulated by this cost-benefit model, potential
      modest cost savings may accrue with implementation of an institution-based
      smoking cessation program through reduced total hospitalization costs that exceed
      the cost of the intervention.

PMID- 18719061
TI  - Functional tricuspid regurgitation in patients with pulmonary hypertension: is
      pulmonary artery pressure the only determinant of regurgitation severity?
AB  - BACKGROUND: Pulmonary hypertension is a common cause of functional tricuspid
      regurgitation (TR), but other factors play a role in determining TR severity. The
      objectives of our study were to determine the distribution of TR severity in
      relation to pulmonary artery systolic pressure (PASP) and to define the
      determinants of TR severity. METHODS: The echocardiographic reports and selected
      echocardiographic studies of patients with echocardiographic estimation of PASP
      were reviewed. Patients with organic tricuspid valve (TV) disease were excluded
      from the analysis. RESULTS: Among 2,139 patients, the frequency of moderate or
      severe TR was progressively greater in patients with higher PASP. Nevertheless,
      TR was only mild in a substantial proportion of patients with high PASP (mild TR
      in 65.4% of patients with PASP 50-69 mm Hg and in 45.6% of patients with PASP
      >or= 70 mm Hg). By multivariate analysis, age, female gender, PASP (odds ratio,
      2.26 per 10-mm Hg increase; 95% confidence interval, 1.95 to 2.61), pacemaker
      lead, right atrial (RA) and right ventricular enlargement, left atrial
      enlargement, and organic mitral valve disease were independently associated with
      greater degrees of TR. In patients with PASP >or= 70 mm Hg, RA size, tricuspid
      annular diameter, and TV tethering area were greater in patients with greater
      degrees of TR. CONCLUSIONS: PASP is a strong determinant of TR severity, but many
      patients with pulmonary hypertension do not exhibit significant TR. In addition
      to PASP, demographic characteristics, mechanical factors, remodeling of the right
      heart cavities, and other factors (possibly reflecting the presence of atrial
      fibrillation or occult organic TV disease) are predictive of TR severity.

PMID- 18719062
TI  - Urban residence is associated with bronchial hyperresponsiveness in Italian
      general population samples.
AB  - BACKGROUND: The role of different risk factors for bronchial hyperresponsiveness
      (BHR), such as gender, atopy, IgE, and environmental factors (smoking,
      occupational exposure, infections), has been described. Indoor and outdoor
      pollution play an important role too, but few studies have analyzed the
      association with BHR. The aim of this study was to assess the effect of urban
      residence on BHR. METHODS: We studied two general population samples enrolled in
      two cross-sectional epidemiological studies performed in Northern Italy (Po
      Delta, rural area) and Central Italy (Pisa, urban area). We analyzed 2,760
      subjects (age range, 8 to 74 years). We performed analysis of variance and
      logistic regression analysis using ln slope of the dose-response curve of the
      methacholine challenge test as dependent variable, and sex, age, smoking habits,
      respiratory symptoms, skin-prick test results, IgE value, residence, and airway
      caliber as independent variables. RESULTS: The mean value of ln slope of the dose
      response curve adjusted for initial airways caliber (by baseline FEV(1)
      percentage of predicted value) was significantly higher in female subjects, in
      smokers, in subjects with respiratory symptoms, in younger and older ages, in
      subjects with high values of IgE, and in subjects with positive skin-prick test
      results. After controlling for the independent effects of all these variables,
      living in urban area was an independent risk factor for having BHR (odds ratio,
      1.41; 95% confidence interval, 1.13 to 1.76). CONCLUSION: Living in urban area is
      a risk factor for increased bronchial responsiveness.

PMID- 18719063
TI  - Obesity and pulmonary complications in critically injured adults.
AB  - BACKGROUND: Pulmonary complications following injury significantly contribute to
      subsequent mortality. Obese patients have preexisting risk factors for pulmonary
      complications, and are at risk for these complications following elective
      surgery. Whether or not obesity contributes to pulmonary complications after
      critical injury is poorly understood. METHODS: A secondary analysis of a
      prospective cohort study of critically injured adults requiring at least 48 h of
      intensive care was performed. Patients were classified into the following body
      mass index groups: < or = 18.5 kg/m2 (underweight); 18.5 to 24.9 kg/m2 (normal);
      25 to 29.9 kg/m2 (overweight); 30.0 to 39.9 kg/m2 (obese); and > or = 40.0 kg/m2
      (severely obese). Outcomes included the rates of ARDS and pneumonia, the
      placement of a tracheostomy tube, and in-hospital mortality rate. RESULTS: A
      total of 1,291 patients were available for analysis, and 30% of these patients
      were classified as either obese or severely obese. The age-, gender-, and
      severity-adjusted rate of ARDS was lower in severely obese patients (odds ratio,
      0.36; 95% confidence interval [CI], 0.13 to 0.99) compared to normal weight
      patients. The rates of pneumonia (37%), tracheostomy (10%), and in-hospital
      mortality (11%) did not differ among the groups. Despite no difference in
      pulmonary complications, the severely obese group had an ICU length of stay that
      was 4.8 days (95% CI, 1.8 to 7.7 days) longer than the normal weight group.
      CONCLUSION: Obesity does not appear to be an independent risk factor for
      increased pulmonary complications after critical injury, but severely obese
      patients are likely to require longer ICU stays.

PMID- 18719064
TI  - Early microbiological response to linezolid vs vancomycin in ventilator
      associated pneumonia due to methicillin-resistant Staphylococcus aureus.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause
      of ventilator-associated pneumonia (VAP). This prospective, open-label,
      multicenter clinical trial compared the early microbiological efficacy of
      linezolid (LZD) therapy with that of vancomycin (VAN) therapy in patients with
      MRSA VAP. METHODS: A total of 149 patients with suspected MRSA VAP were
      randomized to receive either LZD, 600 mg, or VAN, 1 g every 12 h. Patients with
      baseline bronchoscopic BAL (BBAL) fluid quantitative culture findings that were
      positive for MRSA (>or= 10(4) cfu/mL) comprised the study population. The primary
      outcome was microbiological response (<or= 10(2) cfu/mL) in a second BBAL
      performed 72 to 96 h following the start of treatment. RESULTS: Thirty LZD
      treated patients and 20 VAN-treated patients had microbiologically confirmed MRSA
      at baseline; 23 and 19 patients, respectively, underwent repeat BBAL. While a
      greater number of LZD-treated patients than VAN-treated patients achieved a
      microbiological cure (56.5% vs 47.4%, respectively; p = 0.757; 95% confidence
      interval, -21.1 to 39.4), this difference was not statistically significant.
      Nonstatistically significant differences were also seen for LZD-treated patients
      vs VAN-treated patients in terms of clinical cure (66.7% vs 52.9%, respectively),
      survival rate (86.7% vs 70.0%, respectively), and the mean duration of
      ventilation (10.4 vs 14.3 d, respectively), hospitalization (18.8 vs 20.1 d,
      respectively), ICU stay (12.2 vs 16.2 d, respectively), and time spent alive and
      not receiving mechanical ventilation (15.5 vs 11.1 d, respectively). Three
      patients who had been extubated prior to undergoing repeat BBAL had been
      randomized to receive LZD therapy. CONCLUSION: Early microbiological cure rates
      were not statistically significantly higher with LZD therapy than with VAN
      therapy despite trends in all secondary clinical outcomes favoring LZD therapy.
      These results suggest that any beneficial effect of LZD therapy may be due to
      factors other than increased bacterial clearance. TRIAL REGISTRATION:
      Clinicaltrials.gov Identifier: NCT00572559.

PMID- 18719065
TI  - The possible role of hematopoietic cell kinase in the pathophysiology of COPD.
AB  - BACKGROUND: Hematopoietic cell kinase (Hck) is a myeloid cell-specific tyrosine
      kinase, which is known to induce neutrophil infiltration to the lungs. Although
      the overexpression of Hck causes emphysema-like histologic changes in mice, its
      expression and activity in patients with COPD are unclear. METHOD: The aim of
      this study was to clarify the expression and activity of Hck in neutrophils from
      COPD patients, and to investigate the association between the degree of Hck
      expression and the lung function parameters in COPD patients. Peripheral blood
      neutrophils were isolated from 22 patients with COPD and 9 healthy subjects
      (HSs). The protein levels of Hck and phosphorylated Hck were assessed, and the
      correlation with various background characteristics was evaluated. RESULTS: The
      Hck protein level was significantly higher in neutrophils from COPD patients
      compared with HSs (COPD patients, 1.094; HSs, 0.801; p < 0.05). A significant
      positive correlation was observed between the protein level of Hck and the
      surface expression of the integrin molecule CD-11b (r = 0.540; p < 0.01) or CXC
      chemokine receptor-1 (r = 0.432; p < 0.05). In contrast, there was no difference
      in the phosphorylation of the Hck protein between COPD patients and HSs.
      CONCLUSION: The Hck protein level in peripheral blood neutrophils was increased
      in COPD patients, suggesting that Hck might have an important role in the
      neutrophil function and play a key role in the pathophysiology of COPD.

PMID- 18719066
TI  - Permselectivity of blood follicle barriers in mouse ovaries of the mifepristone
      induced polycystic ovary model revealed by in vivo cryotechnique.
AB  - Despite the potential association of polycystic ovary (PCO) syndrome with
      hemodynamic changes, follicular microenvironment and the involvement of blood
      follicle barriers (BFB), a histopathological examination has been hampered by
      artifacts caused by conventional preparation methods. In this study, mouse
      ovaries of a mifepristone-induced PCO model were morphologically and
      immunohistochemically examined by in vivo cryotechnique (IVCT), which prevents
      those technical artifacts. Ovarian specimens of PCO model mice were prepared by
      IVCT or the conventional perfusion fixation after s.c. injection of mifepristone.
      Their histology and immunolocalization of plasma proteins, including albumin
      (molecular mass, 69 kDa), immunoglobulin G (IgG, 150 kDa), inter-alpha-trypsin
      inhibitor (ITI, 220 kDa), fibrinogen (340 kDa), and IgM (900 kDa), were examined.
      In the PCO model, enlarged blood vessels with abundant blood flow were observed
      in addition to cystic follicles with degenerative membrana granulosa. The
      immunolocalization of albumin and IgM in the PCO model were similar to those in
      normal mice. Albumin immunolocalized in the blood vessels, interstitium or
      follicles, and IgM was mostly restricted within the blood vessels. In contrast,
      immunolocalization of IgG, ITI, and fibrinogen changed in the PCO model. Both IgG
      and ITI were clearly blocked by follicular basement membranes, and hardly
      observed in the membrana granulosa, though fibrinogen was mostly observed within
      blood vessels. These findings suggest that increased blood flow and enhanced
      selectivity of molecular permeation through the BFB are prominent features in the
      PCO ovaries, and changes in hemodynamic conditions and permselectivity of BFB are
      involved in the pathogenesis and pathophysiology of PCO syndrome.

PMID- 18719067
TI  - Use of prescription and nonprescription medications and supplements by cancer
      patients during chemotherapy: questionnaire validation.
AB  - BACKGROUND: Cancer patients take medications for coexisting disease and self
      medicate with over-the-counter drugs (OTCs). A complete analysis of the use of
      prescription drugs, OTCs, and supplements during cancer treatment has never been
      done. METHODS: The study developed and validated a self-administered
      questionnaire on the use of concomitant medications by patients undergoing
      treatment with chemotherapy. The questionnaire listed 510 prescription
      medications, OTCs, and supplements (including vitamins, minerals, and herbs).
      Fifty-two subjects completed the questionnaire while visiting the infusion clinic
      to receive chemotherapy. On a subsequent visit the subjects brought their
      medications to the clinic and a pharmacist reviewed their completed
      questionnaire. RESULTS: Ninety-six percent of the subjects reported taking
      prescription medications within 3 days prior to chemotherapy, 71% reported taking
      OTCs and 69% reported use of supplements. The subjects took an average of 5.5
      (range 0-13) prescription drugs, 2.2 (0-20) OTCs, and 1.9 (0-11) supplements.
      Twenty-one drugs were each taken by at least 10% of the subjects. Acetaminophen
      was taken by 59.6% of the subjects. One subject reported taking five
      acetaminophen-containing drugs. The questionnaire's sensitivity was 92.0%,
      specificity 99.9%. CONCLUSION: Within 3 days prior to chemotherapy, subjects took
      an average of 9.6 concomitant medications, many of which alter drug metabolism
      and or disposition. In clinical trials, multivariate analysis of all concomitant
      medications could add to clinically relevant data to identify drug interactions
      that negate or potentiate the efficacy of cancer treatment regimens. In some
      instances, apparent resistance of tumors to chemotherapy may be the result of
      drug interactions.

PMID- 18719068
TI  - Screening and management of osteoporosis in breast cancer patients on aromatase
      inhibitors.
AB  - OBJECTIVE: Breast cancer patients are at an increased risk of osteoporosis due to
      age, cancer, chemotherapy, and aromatase inhibitor therapy. This retrospective
      review determined if patients treated with aromatase inhibitors received
      appropriate screening and management for osteoporosis. DESIGN: University of
      Colorado Cancer Center breast cancer patients treated with aromatase inhibitor
      therapy during July 2005 through July 2006 were studied. Data was collected for
      each patient from the time of breast cancer diagnosis up to April 2007. The study
      endpoints included (1) appropriate screening for osteoporosis, (2) incidence of
      osteoporosis diagnosis, and (3) initiation of appropriate drug therapy for bone
      loss. Appropriate management was defined as adherence to the 2003 American
      Society of Clinical Oncology guidelines for bone health issues in women with
      breast cancer. RESULTS: Of the 54 patients included in this study, 12 (22.2%) had
      no DEXA scans documented, 22 (40.7%) patients received a baseline DEXA scan and 8
      (14.8%) patients received baseline and yearly DEXA scans. During the study
      timeline, 26 (48%) patients were diagnosed with osteopenia and 4 (7%) patients
      were diagnosed with osteoporosis. Forty-one (75.9%) patients received calcium and
      vitamin D therapy. Bisphosphonate therapy was received by less than one-third of
      the osteopenic patients and three-fourths of the osteoporotic patients.
      CONCLUSIONS: The majority of patients were not adequately screened which may have
      falsely lowered the diagnosis of osteoporosis resulting in omission of drug
      therapy. All high-risk patients should receive calcium and vitamin D therapy and
      be evaluated for bisphosphonate therapy. Screening and medical management for
      osteoporosis in breast cancer patients on aromatase inhibitors is an important
      area for clinical intervention.

PMID- 18719069
TI  - Pharmaceutical care in an inpatient pediatric hematopoietic stem cell transplant
      service.
AB  - INTRODUCTION: Hematopoietic stem cell transplant patients represent a population
      at high risk for drug-related problems. Our objective is to describe pharmacist
      interventions in a hematopoietic stem cell transplant pediatric unit. METHODS AND
      PATIENTS. The Hematopoietic Stem Cell Transplant Unit of the Centre Hospitalier
      Universitaire Sainte-Justine performs around 50 hematopoietic stem cell
      transplants per year. During a pharmaceutical care specialized residency program,
      a French pharmacist participated in certain clinical activities. Drug-related
      problems and clinical interventions were compiled over 31 nonconsecutive days
      using a tool developed by the Societe Francaise de Pharmacie Clinique. Data
      concerning patients, drugs, intervention, documentation, approval (if needed),
      and estimated impact were compiled. RESULTS: During the 31-day period, 525
      interventions were collected (16.9 +/- 3.7 per day), targeting 29 patients. The
      main drug-related problems were adverse drug reactions (N = 125, 23.8%),
      untreated indication (N = 92, 17.5%) and failure to receive drug (N = 89, 17.0%).
      The pharmacist's interventions concerned mainly dose adjustment (N = 174, 33.1%)
      and drug monitoring (N = 132, 25.1%). Among the 324 (61.7%) interventions
      requiring a physician's approval, 302 (93.2%) were accepted without any change.
      CONCLUSION: A pharmacist is able to perform clinically relevant interventions in
      a hematopoietic stem cell transplant unit, given the complexity of the
      pharmacotherapy. Our description of drug-related problems and interventions may
      help other pharmacists already working or developing pharmaceutical care in a
      hematopoietic stem cell transplant unit to compare their practice and it is one
      of the few reported in the literature.

PMID- 18719070
TI  - Managing reduced methotrexate clearance in a patient with a heterozygous
      methylenetetrahydrofolate reductase gene polymorphism.
AB  - High dose methotrexate has become one of the treatments of choice for patients
      with primary CNS lymphomas due to its ability to penetrate the blood-brain
      barrier. A potentially serious complication of this therapy is methotrexate
      related nephrotoxicity. We report the case of a patient with a common genetic
      polymorphism that may have predisposed this patient experience clinically
      significant toxicity from systemic folate depletion. After the first cycle of
      chemotherapy that included high dose methotrexate, the patient's serum creatinine
      rose and the patient's methotrexate level remained above the toxic range for six
      days. On cycle two, the patient was treated with a 25% dose reduction in
      methotrexate and more aggressive hydration and alkalization. With this alteration
      in the regimen, the patient was able to receive six more cycles and had a
      complete radiographic tumor response in the brain and a disappearance of tumor
      cells in the CSF without any further renal complications. This case report
      illustrates the feasibility of administering high dose methotrexate with
      modifications as a treatment of choice in individuals with
      methylenetetrahydrofolate reductase gene mutations.

PMID- 18719071
TI  - Characterization of the occurrence of ifosfamide-induced neurotoxicity with
      concomitant aprepitant.
AB  - PURPOSE: Ifosfamide is metabolized by the cytochrome P450 system to its active
      form, ifosforamide mustard. A potential side effect is neurotoxicity, often
      manifesting as confusion, hallucination, or seizure. Aprepitant, a neurokinin-1
      inhibitor, is recommended for highly and moderately emetogenic chemotherapy
      regimens and may interfere with the metabolism of ifosfamide as it inhibits
      CYP3A4. The objective of the study is to identify if an increase in the incidence
      of neurotoxicity may be associated with the use of aprepitant with concomitant
      ifosfamide. METHODS: A retrospective study of inpatients with sarcoma who
      received a two or four-day regimen of MAI (mesna, doxorubicin, and ifosfamide)
      between January 1, 2004 and December 31, 2006 was conducted. Data collection
      focused on characterizing neurotoxicity of patients receiving ifosfamide with or
      without aprepitant. Correlation between serum creatinine, albumin, liver function
      tests, age, gender, and total doses of ifosfamide was examined. RESULTS: A total
      of 45 patients received ifosfamide of which 23 (51%) were male and 24 (53%)
      received aprepitant. All baseline characteristics were similar for those who
      received aprepitant versus those who did not. No significant differences were
      noted between patients with or without neurotoxicity for age, gender, or liver
      enzymes. Eight patients (18%) of 45 developed neurotoxicity of which six (75%) of
      those patients also received aprepitant. A trend of increased occurrence of
      neurotoxicity was noted with aprepitant administration (6 vs. 2 patients
      respectively, p = 0.176), although a statistical difference was not observed. A
      relative risk of 2.6 (95% CI, 0.47-26.6) was associated with the addition of
      aprepitant. CONCLUSIONS: An increased risk was identified for ifosfamide-induced
      neurotoxicity associated with aprepitant use; however, the observed difference
      was not statistically significant. The necessity of aprepitant given in
      association with ifosfamide may need to be reconsidered due to this risk.

PMID- 18719072
TI  - Identification of the invariant chain (CD74) as an angiotensin AGTR1-interacting
      protein.
AB  - Little is known about the protein-protein interactions that regulate the
      trafficking of the angiotensin II type I receptor (AGTR1) through the
      biosynthetic pathway. The membrane-proximal region of the cytoplasmic tail of the
      AGTR1 has been identified by site-directed mutagenesis studies as an essential
      site for normal AGTR1 folding and surface expression. Based on yeast two-hybrid
      screening of a human kidney cDNA library with the AGTR1 carboxyl-terminal tail as
      a bait, we identified the invariant chain (CD74) as a novel interacting protein.
      This association was confirmed by co-immunoprecipitation and co-localization
      studies. The binding site for CD74 on the AGTR1 carboxyl-terminal tail was
      localized to a site previously identified as important for the exit of the AGTR1
      from the endoplasmic reticulum (ER), and conserved in many G protein-coupled
      receptors. Transient co-expression of CD74 with the AGTR1 in CHO-K1 cells
      consistently reduced the AGTR1 density at the cell surface. Furthermore, the
      interaction of CD74 with the carboxyl-terminal tail of the AGTR1 caused its
      retention in the ER and promoted its proteasomal degradation. These observations
      indicate that CD74 and the AGTR1 become associated in the early biosynthetic
      pathway, and that CD74 is a negative regulator of AGTR1 expression.

PMID- 18719073
TI  - Long-term moderate ethanol consumption restores insulin sensitivity in high-fat
      fed rats by increasing SLC2A4 (GLUT4) in the adipose tissue by AMP-activated
      protein kinase activation.
AB  - The sole effect of either saturated fatty acid or moderate ethanol consumption on
      SLC2A4 (GLUT4) expression is widely reported but the combined effects of them
      remain obscure. Here, we observed their combined effects on SLC2A4 expression,
      explored the underlying mechanism mediated by AMP-activated protein kinase alpha
      (PRKAA2) and myocyte enhancer factor 2 (MEF2) both in vivo and in vitro. In the
      in vivo experiments, 36 male Wistar rats, divided into three groups, were fed
      with normal diet, high-fat (HF) diet, or HF diet plus ethanol for 22 weeks. We
      measured the expressions of total-PRKAA2 (T-PRKAA2), phosphorylated-PRKAA2
      (pPRKAA2, activated form of PRKAA2), MEF2, and SLC2A4 in epididymal adipose
      tissues. In the in vitro experiments, primary adipocytes, isolated from normal
      Wistar rats, were incubated in the presence or absence of palmitate, ethanol, and
      compound C (an PRKAA2 inhibitor) for 1 h. Thereafter, T-PRKAA2, pPRKAA2, MEF2,
      and SLC2A4 expressions were measured. We found that both HF diet and in vitro
      exposition to palmitate impaired SLC2A4 expression in rat adipocytes with a
      parallel reduction in PRKAA2 activation and MEF2 expression. This impairment was
      reversed by ethanol administration. We further demonstrated that ethanol-mediated
      PRKAA2 activation stimulates MEF2 and SLC2A4 expressions in adipocytes, as
      evidenced by compound C blockade of these effects. In summary, long-term moderate
      ethanol consumption reversed the adverse effect of saturated fatty acid on SLC2A4
      expression in adipocytes, which was likely to be a result of PRKAA2 activation
      and subsequent up-regulation of MEF2 and SLC2A4 expressions.

PMID- 18719074
TI  - Inhibition of ADP-ribosyl cyclase attenuates angiotensin II-induced cardiac
      hypertrophy.
AB  - AIMS: Here, we report the discovery of a small molecule inhibitor, 2,2'
      dihydroxyazobenzene (DAB), of ADP ribosyl cyclase (ADPR-cyclase) and showed that
      this inhibitor attenuated angiotensin (Ang) II-induced hypertrophic responses.
      METHODS: and results The intracellular concentration of free Ca(2+) [Ca(2+)](i)
      in adult rat cardiomyocytes was measured by using a confocal microscope. Cardiac
      hypertrophy was induced by the two-kidney one-clip (2K1C) method. Hypertrophy was
      determined by de novo protein synthesis, cell volume, echocardiography, nuclear
      translocation of nuclear factor of activated T-cells, and transforming growth
      factor-beta1 protein expression. Treatment of cardiomyocytes with Ang II
      generated a biphasic [Ca(2+)](i) increase that included an initial Ca(2+)peak and
      sustained Ca(2+) rise via inositol trisphosphate and cyclic ADP-ribose (cADPR)
      formation, respectively. A cADPR antagonistic analogue, 8-Br-cADPR, and an ADPR
      cyclase inhibitor, DAB, blocked the sustained Ca(2+) signal, but not the initial
      Ca(2+) rise. Furthermore, DAB significantly inhibited Ang II-mediated cADPR
      formation and hypertrophic responses in vitro. Echocardiography and histological
      examination revealed significant cardiac hypertrophy in 2K1C rats that was
      potently inhibited by treatment with DAB. In addition, the hypertrophic responses
      induced by Ang II in vitro were significantly increased by 2K1C, and DAB
      treatment reversed these hypertrophic responses to the levels of sham Control.
      CONCLUSION: ADPR-cyclase is an important mediator of cardiac hypertrophy, and
      inhibition of ADPR-cyclase by DAB may provide a new therapeutic strategy for
      cardiac diseases.

PMID- 18719075
TI  - Cost-effectiveness of the Australian National Tobacco Campaign.
AB  - BACKGROUND: The Australian National Tobacco Campaign (NTC) was an intensive mass
      media anti-smoking campaign, the first phase of which commenced in 1997, cost
      around $A9 million, and reduced smoking prevalence by 1.4%. OBJECTIVE: To assess
      the cost-effectiveness of phase one of the NTC, which ran from June to November
      1997. DESIGN AND STUDY POPULATION: The quit benefits model (QBM), a Markov-cycle
      simulation model was used to predict the benefits of smoking cessation for the
      estimated 190 000 quitters from the time of quitting until death, censored at age
      85 years. Measures of effectiveness were cases of lung cancer, acute myocardial
      infarction (AMI), stroke and chronic obstructive pulmonary disease (COPD)
      avoided; deaths prevented, and life-years and quality-adjusted life-years (QALYs)
      gained. The savings in healthcare costs through prevention of the four specified
      smoking-associated diseases were estimated. Future costs, life-years and QALYS
      were discounted at 3% per year. RESULTS: The QBM predicted that the NTC avoided
      over 32 000 cases of COPD, 11 000 cases of AMI, 10 000 cases of lung cancer, and
      2500 cases of stroke. Prevention of around 55 000 deaths, gains of 323 000 life
      years and 407 000 QALYs, and healthcare cost savings of $A740.6 million were
      predicted. The NTC was therefore both cost saving and effective. CONCLUSIONS: As
      well as reducing smoking prevalence, the NTC was unequivocally cost-effective.

PMID- 18719076
TI  - Evidence of retinal vascular narrowing in glaucomatous eyes in an Asian
      population.
AB  - PURPOSE: To examine the relationship between retinal vascular caliber and
      glaucoma in an Asian population. METHODS: A population-based, cross-sectional
      study of 3019 persons of Asian Malay ethnicity aged 40 to 80 years residing in
      Singapore. All participants had dilated digital retinal photographs taken of both
      eyes. From these, retinal vascular caliber was measured with a computer-based
      technique according to a standardized protocol. Glaucoma was diagnosed based on
      the International Society of Geographic and Epidemiologic Ophthalmology
      classification and included people with glaucomatous optic neuropathy and
      compatible visual field loss. RESULTS: There were 127 (4.2%) participants with
      glaucoma. Mean retinal arteriolar and venular calibers were significantly
      narrower in persons with than in those without glaucoma (136.4 microm vs. 139.7
      microm, P = 0.02 and 209.2 microm vs. 219.7 microm, P < 0.001, respectively).
      After adjusting for age, sex, smoking, IOP, and other vascular risk factors,
      persons with narrower retinal arteriolar and venular caliber were more likely to
      have glaucoma (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.07-1.56 and
      OR, 1.49; 95% CI, 1.24-1.79, for each SD reduction in arteriolar and venular
      caliber, respectively) and a vertical cup-to-disc ratio >or= 0.7 (OR, 1.35; 95%
      CI, 1.12-1.63 and OR, 1.65; 95% CI, 1.38-1.98, respectively). Retinal vascular
      caliber was not associated with intraocular pressure. CONCLUSIONS: These findings
      support an association of narrower retinal arteriolar and venular caliber changes
      with glaucomatous optic neuropathy, independent of intraocular pressure.

PMID- 18719077
TI  - Multifocal ERG responses in infants.
AB  - PURPOSE: To assess function of the central retina in 10-week-old infants,
      multifocal electroretinograms (mfERGs) were recorded. mfERG responses represent
      postreceptor retinal activity. METHODS: In infants (n = 23) and adults (n = 10),
      mfERG responses to both unscaled and scaled 61 hexagon arrays were recorded.
      Amplitude and implicit time of negative (N(1), N(2)) and positive (P(1)) peaks of
      the first-order kernel were examined. The response from the entire area
      stimulated and responses to concentric rings were analyzed separately. The
      overall averaged response of the first slice of the second-order kernel was also
      evaluated. Results from infants and adults were compared. RESULTS: Amplitudes of
      the infants' responses (N(1), P(1), N(2)) were significantly smaller and implicit
      times were significantly longer than those of adults. In infants, amplitude and
      implicit time varied little with eccentricity. In adults, amplitude decreased
      with eccentricity, whereas implicit time varied little. In infants, the second
      order kernel was relatively more attenuated than the first-order kernel.
      CONCLUSIONS: The infants' mfERG responses indicated immaturities of processing in
      the central retina. Infant-adult differences in the distribution of cones and
      bipolar cells may account for the results.

PMID- 18719078
TI  - Oncogenic mutations in GNAQ occur early in uveal melanoma.
AB  - PURPOSE: Early/initiating oncogenic mutations have been identified for many
      cancers, but such mutations remain unidentified in uveal melanoma (UM). An
      extensive search for such mutations was undertaken, focusing on the RAF/MEK/ERK
      pathway, which is often the target of initiating mutations in other types of
      cancer. METHODS: DNA samples from primary UMs were analyzed for mutations in 24
      potential oncogenes that affect the RAF/MEK/ERK pathway. For GNAQ, a stimulatory
      alpha(q) G-protein subunit which was recently found to be mutated in UMs,
      resequencing was expanded to include 67 primary UMs and 22 peripheral blood
      samples. GNAQ status was analyzed for association with clinical, pathologic,
      chromosomal, immunohistochemical, and transcriptional features. RESULTS:
      Activating mutations at codon 209 were identified in GNAQ in 33 (49%) of 67
      primary UMs, including 2 (22%) of 9 iris melanomas and 31 (54%) of 58 posterior
      UMs. No mutations were found in the other 23 potential oncogenes. GNAQ mutations
      were not found in normal blood DNA samples. Consistent with GNAQ mutation being
      an early or initiating event, this mutation was not associated with any clinical,
      pathologic, or molecular features associated with late tumor progression.
      CONCLUSIONS: GNAQ mutations occur in about half of UMs, representing the most
      common known oncogenic mutation in this cancer. The presence of this mutation in
      tumors at all stages of malignant progression suggests that it is an early event
      in UM. Mutations in this G-protein-coupled receptor provide new insights into UM
      pathogenesis and could lead to new therapeutic possibilities.

PMID- 18719080
TI  - Targeted knockout of the mouse betaB2-crystallin gene (Crybb2) induces age
      related cataract.
AB  - PURPOSE: The betaB2-crystallin gene (Crybb2) is expressed at an increasing level
      in the postnatal lens cortex. It has been assumed that the gene functions as
      structural protein, although this has not been directly tested. Here the in vivo
      functions of betaB2-crystallin are examined via the generation of mice with a
      targeted disruption of Crybb2. METHODS: Gene targeting in embryonic stem cells
      was used to generate mouse lines in which Crybb2 was deleted. Gene structure and
      protein expression were analyzed by PCR, immunoblot, and two-dimensional gel
      electrophoresis. Knockout mice were screened for cataract with slit lamp
      biomicroscopy. Microstructure of lens was analyzed by scanning and transmission
      electron microscopy. The resistance of crystallins in knockout mice to heat
      induced denaturation and oxidative stress was examined. RESULTS: The lens
      appeared to develop normally in the first months of life. In older animals, the
      weight and axial diameter of the lenses of knockout mice were significantly
      smaller than in wild-type mice. Cataracts were formed in the posterior and
      anterior cortex several months after birth and cataract severity increased with
      age. The thermal stability of the supernatant of a lens homogenate was mildly
      compromised. The knockout lenses also showed decreased resistance to oxidative
      stress. CONCLUSIONS: BetaB2-crystallin is not essential for the normal
      development of a transparent lens in the mouse. It plays an increasingly
      important role in maintaining the transparency of the lens after birth, possibly
      by interacting with other crystallins to increase their resistance to thermal
      denaturation and oxidative stress.

PMID- 18719079
TI  - In vivo human choroidal thickness measurements: evidence for diurnal
      fluctuations.
AB  - PURPOSE: The authors applied partial coherence interferometry (PCI) to estimate
      the thickness of the human choroid in vivo and to learn whether it fluctuates
      during the day. METHODS: By applying signal processing techniques to existing PCI
      tracings of human ocular axial length measurements, a signal modeling algorithm
      was developed and validated to determine the position and variability of a
      postretinal peak that, by analogy to animal studies, likely corresponds to the
      choroidal/scleral interface. The algorithm then was applied to diurnal axial eye
      length datasets. RESULTS: The postretinal peak was identified in 28% of subjects
      in the development and validation datasets, with mean subfoveal choroidal
      thicknesses of 307 and 293 microm, respectively. Twenty-eight of 40 diurnal PCI
      datasets had at least two time points with identifiable postretinal peaks,
      yielding a mean choroidal thickness of 426 microm and a mean high-low difference
      in choroidal thickness of 59.5 +/- 24.2 microm (range, 25.9-103 microm). The
      diurnal choroidal thickness fluctuation was larger than twice the SE of
      measurement (24.5 microm) in 16 of these 28 datasets. Axial length and choroidal
      thickness tended to fluctuate in antiphase. CONCLUSIONS: Signal processing
      techniques provide choroidal thickness estimates in many, but not all, PCI
      datasets of axial eye measurements. Based on eyes with identifiable postretinal
      peaks at more than one time in a day, choroidal thickness varied over the day.
      Because of the established role of the choroid in retinal function and its
      possible role in regulating eye growth, further development and refinement of
      clinical methods to measure its thickness are warranted.

PMID- 18719081
TI  - Effect of dual endothelin receptor blockade on ocular blood flow in patients with
      glaucoma and healthy subjects.
AB  - PURPOSE: Several lines of evidence indicate that altered blood flow regulation
      may contribute to the pathogenesis of glaucomatous optic neuropathy. Recent data
      support the hypothesis that the endothelin system is involved in the processes
      that lead to vascular dysregulation in glaucoma. This study was conducted to test
      the hypothesis that bosentan, a dual endothelin receptor antagonist, increases
      ocular blood flow in patients with glaucoma. METHODS: Fourteen patients with
      primary open-angle glaucoma and 14 sex- and age-matched healthy volunteers were
      included. Both groups received bosentan 500 mg daily for 8 days. Ocular
      hemodynamics were assessed at baseline and on the last study day. Retinal vessel
      diameters and retinal red blood cell velocity were recorded with a retinal vessel
      analyser and laser Doppler velocimetry, respectively. Choroidal and optic nerve
      head blood flow were measured with laser Doppler flowmetry. RESULTS: Retinal
      arteries and veins showed a significant dilatation after administration of
      bosentan in both groups (+5%-8%). Retinal blood velocity and retinal blood flow
      increased up to +45% after administration of bosentan in both patients and
      healthy subjects. Administration of bosentan increased choroidal (+12%-17%) and
      optic nerve head blood flow (+11%-24%) in both groups. The effect of bosentan on
      ocular blood flow parameters was comparable between the two groups. CONCLUSIONS:
      The data from the present study indicate that dual inhibition of endothelin
      receptors increases ocular blood flow in patients with glaucoma and healthy
      subjects. Further studies are needed to study the dose-response relationship of
      this effect and to characterize the role of endothelin receptor subtypes.

PMID- 18719082
TI  - Inhibitory effects of glucosamine on endotoxin-induced uveitis in Lewis rats.
AB  - PURPOSE: Glucosamine sulfate (GS) is a naturally occurring sugar that exerts
      immunosuppressive effects in vitro and in vivo. The authors investigated whether
      GS modulates the inflammatory reaction in endotoxin-induced uveitis (EIU) of rats
      and the mechanisms by which it exerts its effects. METHODS: Two-hundred
      micrograms of lipopolysaccharide (LPS) was injected subcutaneously into Lewis
      rats to induce EIU. Doses of GS (10, 100, or 1000 mg/kg) were divided into three
      aliquots and administered intraperitoneally 30 minutes before LPS injection,
      concurrently with LPS injection, and 30 minutes after LPS injection. Twenty-four
      hours after LPS injection, aqueous humor was collected for cell counting and
      measurement of protein concentration. Immunohistochemical staining of the iris
      ciliary body was performed to evaluate the effects of GS on intercellular
      adhesion molecule (ICAM)-1 and nuclear factor (NF)-kappaB activation and to
      demonstrate macrophage infiltration. The effects of various doses of GS
      pretreatment were also examined using a mouse macrophage cell line (RAW264.7
      cells) and LPS stimulation. Levels of prostaglandin (PG)-E2 and nitric oxide (NO)
      were determined. Expression of inducible NO synthase (iNOS) and cyclooxygenase
      (COX)-2 were measured using Western blot analysis. The effect of GS on LPS
      induced NF-kappaB activation in RAW cells was also examined. RESULTS: Cell
      counting and analysis of protein concentration in aqueous humor revealed that GS
      suppressed EIU in rats treated with a high dose of GS (1000 mg/kg).
      Immunohistochemistry showed that treatment with GS reduced ICAM-1 expression and
      suppressed activation of NF-kappaB in the iris-ciliary body. The main
      inflammatory cells in the iris-ciliary body during EIU were macrophages. In LPS
      stimulated macrophage RAW cell culture, GS inhibited the production of NO and PG
      E2, the expression of iNOS and COX-2, and the activation of NF-kappaB.
      CONCLUSIONS: GS suppresses EIU in rats by blockading the NF-kappaB-dependent
      signaling pathway and the subsequent production of ICAM-1 and proinflammatory
      mediators. This study has extended the authors' previous observation that GS is a
      potentially important compound for reducing ICAM-1-mediated inflammatory effects
      in the eye.

PMID- 18719083
TI  - Correlation of different circulating endothelial progenitor cells to stages of
      diabetic retinopathy: first in vivo data.
AB  - PURPOSE: To investigate vasculogenic circulating progenitor cells (CPCs),
      endothelial progenitor cells (EPCs), and mature EPCs in patients with type 1
      diabetes mellitus (T1DM) with or without diabetic retinopathy (DR). METHODS: A
      case-control study comparing 90 patients with T1DM with and without DR was
      performed. Patients were studied and staged for retinopathy according to the
      Early Treatment of Diabetic Retinopathy Study (ETDRS) classification. Ninety
      patients were included: 30 without DR (control [CO]), 30 with mild
      nonproliferative DR (mNPDR), 10 with moderate-severe NPDR (msNPDR), 10 with mild
      moderate proliferative diabetic retinopathy (mmPDR), and 10 with high-risk PDR
      (hrPDR). CPCs (CD34/CD133), EPCs (CD34/CD133/CD309), and mature EPCs
      (CD34/CD133/CD309/CD31) were enumerated by flow cytometry. RESULTS: EPCs were
      reduced in mNPDR (114 +/- 66; P < 0.001) and msNPDR (77 +/- 40; P = 0.042)
      compared with CO (244 +/- 115). In contrast, EPCs were unchanged in mmPDR (248 +/
      155) compared with CO. Strikingly, EPCs were augmented in hrPDR (389 +/- 124)
      compared with all other stages. Numbers of undifferentiated progenitor cells
      (CPCs) did not differ among CO, mmPDR, and hrPDR. Augmentation (3x) of mature
      EPCs in hrPDR (325 +/- 118; P < 0.001) compared with CO (100 +/- 49) but against
      all other stages of DR was observed. The percentage of mature EPCs/EPCs was
      augmented in an ETDRS classification-dependent manner. CONCLUSIONS: In patients
      with T1DM with DR, EPCs undergo stage-related regulation. In nonproliferative
      retinopathy, a reduction of EPCs was observed, and in proliferative retinopathy,
      a dramatic increase of mature EPCs was observed.

PMID- 18719084
TI  - Sox2 plays a role in the induction of amacrine and Muller glial cells in mouse
      retinal progenitor cells.
AB  - PURPOSE: The transcription factor Sox2 plays important roles in both human and
      mouse retinal development. Although loss-of-function mutations in Sox2 have been
      studied in mice, gain-of-function experiments in the neural retina have been
      lacking. METHODS: The detailed expression pattern of Sox2 in the developing mouse
      retina was examined by immunohistochemistry. Then, Sox2 was expressed in a
      retinal explant culture prepared from E17 mouse embryos by retrovirus-mediated
      gene transfer to examine its role in retinal development. In addition, shRNA was
      used to suppress Sox2 in a retinal explant using a retrovirus-mediated system.
      RESULTS: Sox2 was expressed throughout the neuroblastic layer in the embryonic
      retina, but only in the inner nuclear layer in the mature retina. Double
      immunostaining revealed that Sox2 was expressed in Muller glial cells and in a
      subset of amacrine cells. Forced expression of Sox2 in a mouse retinal explant
      culture resulted in the dramatic accumulation of amacrine cells in the inner
      nuclear layer; in addition, cells expressing amacrine cell markers were also
      found on the innermost side of the outer nuclear layer. The expression of Pax6,
      which plays an important role in amacrine cell differentiation, was observed in
      the Sox2-expressing cells, and Sox2 activated the Pax6 promoter to drive
      luciferase expression in Y79 cells. A decrease in retinal progenitor cell
      proliferation accompanied these effects. The suppression of Sox2 expression by
      shRNA resulted in a decreased number of cells in the inner nuclear layer.
      CONCLUSIONS: Therefore, ectopic Sox2 expression can induce amacrine cells in the
      mouse retina from stage E17 onward, possibly by facilitating cell cycle exit.

PMID- 18719085
TI  - Emmetropization and eye growth in young aphakic chickens.
AB  - PURPOSE: To establish a chick model to investigate the trends of eye growth and
      emmetropization after early lensectomy for congenital cataract. METHODS: Four
      monocular treatments were applied: lens extraction (LX); sham surgery/-30 D lens;
      LX/+20 D lens; and LX/+30-D lens (nine per group). Lens powers were selected to
      slightly undercorrect or overcorrect the induced hyperopia in LX eyes and to
      induce comparable hyperopia in sham-surgery eyes. Refractive errors and axial
      ocular dimensions were measured over a 28-day period. External ocular dimensions
      were obtained when the eyes were enucleated on the last day. RESULTS: The growth
      patterns of experimental (Exp) eyes varied with the type of manipulation. All
      eyes experiencing hyperopia initially grew more than their fellow eyes and
      exhibited myopic shifts in refraction. The sham/-30 D lens group showed the
      greatest increase in optical axial length, followed by the LX group, and then the
      LX/+20 D lens group. The Exp eyes of the LX/+30 D lens group, which were
      initially slightly myopic, grew least, and showed a small hyperopic shift.
      Lensectomized eyes enlarged more equatorially than axially (i.e., oblate),
      irrespective of the optical treatment applied. CONCLUSIONS: The refractive
      changes observed in young, aphakic eyes are consistent with compensation for the
      defocus experienced, and thus emmetropization. However, differences in the
      effects of lensectomy compared to those of sham surgery raise the possibility
      that the lens is a source of essential growth factors. Alterative optical and
      mechanical explanations are offered for the oblate shapes of aphakic eyes.

PMID- 18719086
TI  - Intracranial pressure in primary open angle glaucoma, normal tension glaucoma,
      and ocular hypertension: a case-control study.
AB  - PURPOSE: To compare intracranial pressure (ICP) in subjects with primary open
      angle glaucoma (POAG), normal-tension glaucoma (NTG; subset of POAG), and ocular
      hypertension (OHT) with that in subjects with no glaucoma. METHODS: The study was
      a retrospective review of medical records of 62,468 subjects who had lumbar
      puncture between 1985 and 2007 at the Mayo Clinic. Of these, 57 POAG subjects, 11
      NTG subjects (subset of POAG), 27 OHT subjects, and 105 control subjects met the
      criteria and were analyzed. A masked comparison of the relationship between ICP
      and other ocular and nonocular variables was performed by using univariate and
      multivariate analyses. RESULTS: ICP was significantly lower in POAG compared with
      age-matched control subjects with no glaucoma (9.1 +/- 0.77 mm Hg vs. 11.8 +/-
      0.71 mm Hg; P < 0.0001). Subjects with NTG also had reduced ICP compared with the
      control subjects (8.7 +/- 1.16 mm Hg vs. 11.8 +/- 0.71 mm Hg; P < 0.01). ICP was
      higher in OHT than in age-matched control subjects (12.6 +/- 0.85 mm Hg vs. 10.6
      +/- 0.81 mm Hg; P < 0.05). CONCLUSIONS: ICP is lower in POAG and NTG and elevated
      in OHT. ICP may play an important role in the development of POAG and NTG and in
      preventing the progression of OHT to POAG. Further prospective and experimental
      studies are warranted to determine whether ICP has a fundamental role in the
      pathogenesis of glaucoma.

PMID- 18719087
TI  - Motion-detection threshold and measures of balance in older adults: the SEE
      Project.
AB  - PURPOSE: The aim of this study was to identify the visual factors associated with
      various levels of balance ability in a population-based study of older adults.
      METHODS: Data for this analysis came from the third round of the Salisbury Eye
      Evaluation population-based cohort study (1505 individuals). Measures of visual
      function including acuity, contrast sensitivity, visual fields, and motion
      detection were obtained. Balance was assessed by determining if participants
      could complete a series of timed stands designed to increase in difficulty. The
      outcome was an unsuccessful stand. Analyses were performed using logistic
      regression with generalized estimating equations with stand type as an indicator
      variable. RESULTS: In a model containing all vision variables, those with worse
      motion-detection threshold were more likely to have an unsuccessful tandem stand
      (odds ratio [OR] = 1.56, 95% CI: 1.13-2.15) and soleo stand (on one foot of
      choice with eyes open and arms out; OR = 3.08, 95% CI: 1.57-6.06) while those
      with worse visual field were more likely to have an unsuccessful tandem stand (OR
      = 1.22, 95% CI: 1.08-1.38) after adjustment. Furthermore, the relationship
      between motion-detection threshold and an unsuccessful stand was stronger for the
      most difficult stand on one foot (the soleo stand) (P = 0.02). CONCLUSIONS:
      Problems with balance in older adults may be due, in part, to decreased ability
      to detect small movements and/or visual field reduction.

PMID- 18719089
TI  - The promise and challenges of population strategies of prevention.

PMID- 18719088
TI  - Visual and cognitive deficits predict stopping or restricting driving: the
      Salisbury Eye Evaluation Driving Study (SEEDS).
AB  - PURPOSE: To determine the visual and other factors that predict stopping or
      restricting driving in older drivers. METHODS: A group of 1425 licensed drivers
      aged 67 to 87 years, who were residents of greater Salisbury, participated. At 1
      year after enrollment, this group was categorized into those who had stopped
      driving, drove only within their neighborhood, or continued to drive beyond their
      neighborhood. At baseline, a battery of structured questionnaires, vision, and
      cognitive tests were administered. Multivariate analysis determined the factors
      predictive of stopping or restricting driving 12 months later. RESULTS: Of the
      1425 enrolled, 1237 (87%) were followed up at 1 year. Excluding those who were
      already limiting their driving at baseline (n = 35), 1.5% (18/1202) had stopped
      and 3.4% (41/1202) had restricted their driving. The women (odds ratio [OR],
      4.01; 95% confidence interval [CI], 2.05-8.20) and those who prefer to be driven
      (OR, 3.91; 95% CI, 1.91-8.00) were more likely to stop or restrict driving.
      Depressive symptoms increased likelihood of restricting or stopping driving (OR,
      1.08; 95% CI, 1.009-1.16 per point Geriatric Depression Scale). Slow visual
      scanning and psychomotor speed (Trail Making Test, Part A: OR, 1.02; 95% CI, 1.01
      1.03), poor visuoconstructional skills (Beery-Buktenica Test of Visual Motor
      Integration: OR, 1.14; 95% CI, 1.05-1.25), and reduced contrast sensitivity (OR,
      1.15; 95% CI, 1.03-1.28) predicted stopping or reducing driving. Visual field
      loss and visual attention were not associated. The effect of vision on changing
      driving behavior was partially mediated by cognition, depression, and baseline
      driving preferences. CONCLUSIONS: In this cohort, contrast sensitivity and
      cognitive function were independently associated with incident cessation or
      restriction of driving space. These data suggest drivers with functional deficits
      make difficult decisions to restrict or stop driving.

PMID- 18719090
TI  - Cohort profile: the Copenhagen School Health Records Register.

PMID- 18719091
TI  - Increased density of tumor-associated macrophages is associated with decreased
      survival in advanced thyroid cancer.
AB  - Thyroid cancers are infiltrated with tumor-associated macrophages (TAMs), yet
      their role in cancer progression is not known. The objectives of this study were
      to characterize the density of TAMs in well-differentiated (WDTC), poorly
      differentiated (PDTC), and anaplastic thyroid cancers (ATC) and to correlate TAM
      density with clinicopathologic parameters. Immunohistochemistry was performed on
      tissue microarray sections from WDTC (n=33), PDTC (n=37), and ATC (n=20) using
      macrophage-specific markers. Electronic medical records were used to gather
      clinical and pathologic data. Follow-up information of PDTC patients was
      available for 0-12 years. In total, 9 out of 33 WDTC (27%), 20 out of 37 PDTC
      (54%), and 19 out of 20 ATC (95%) had an increased density of CD68(+) TAMs (> or
      = 10 per 0.28 mm(2); WDTC versus PDTC, P=0.03; WDTC versus ATC, P<0.0001; PDTC
      versus ATC, P<0.002). Increased TAMs in PDTC was associated with capsular
      invasion (P=0.034), extrathyroidal extension (P=0.009), and decreased cancer
      related survival (P=0.009) compared with PDTC with a low density of TAMs. In
      conclusion, the density of TAMs is increased in advanced thyroid cancers. The
      presence of a high density of TAMs in PDTC correlates with invasion and decreased
      cancer-related survival. These results suggest that TAMs may facilitate tumor
      progression. As novel therapies directed against thyroid tumor cell-specific
      targets are being tested, the potential role of TAMs as potential modulators of
      the thyroid cancer behavior will need to be considered.

PMID- 18719092
TI  - Vitamin D receptor polymorphisms (FokI, BsmI) and breast cancer risk: association
      replication in two case-control studies within French Canadian population.
AB  - Vitamin D has been associated with reduced breast cancer risk. We studied the
      association of two vitamin D receptor (VDR) gene single nucleotide polymorphisms
      restriction enzyme detecting SNP of VDR (FokI and BsmI) with breast cancer risk
      in two independent case-control studies carried out in the same population. The
      modifying effect of family history of breast cancer on this relationship was also
      evaluated. The first and second studies included respectively 718 (255 cases/463
      controls) and 1596 (622 cases/974 controls) women recruited in Quebec City,
      Canada. FokI and BsmI genotypes were assessed. Relative risks of breast cancer
      were estimated by multivariate logistic regression. Compared with homozygotes for
      the common F allele (FF genotype), FokI ff homozygotes had a higher breast cancer
      risk (study 1: odds ratio (OR)=1.22, 95% confidence interval (CI)=0.76-1.95;
      study 2: OR=1.44, 95% CI=1.05-1.99; and combined studies: OR=1.33, 95% CI=1.03
      1.73). Significant interactions were observed between FokI and family history of
      breast cancer in the two studies as well as in the combined analysis (P
      interaction=0.031, 0.050 and 0.0059 respectively). Among women without family
      history, odds ratios were 1.00, 1.27 (95% CI=1.02-1.58) and 1.57 (95% CI=1.18
      2.10) respectively for FF, Ff and ff carriers (P(trend)=0.0013). BsmI Bb+bb
      genotypes were associated with a weak non-significant increased risk in the two
      studies (combined OR=1.22, 95% CI=0.95-1.57) without interaction with family
      history. Results support the idea that vitamin D, through its signalling pathway,
      can affect breast cancer risk. They also suggest that variability in observed
      associations between VDR FokI and breast cancer from different studies may partly
      be explained by the proportion of study subjects with a family history of breast
      cancer.

PMID- 18719093
TI  - Pathogen corruption and site-directed recombination at a plant disease resistance
      gene cluster.
AB  - The Pc locus of sorghum (Sorghum bicolor) determines dominant sensitivity to a
      host-selective toxin produced by the fungal pathogen Periconia circinata. The Pc
      region was cloned by a map-based approach and found to contain three tandemly
      repeated genes with the structures of nucleotide binding site-leucine-rich repeat
      (NBS-LRR) disease resistance genes. Thirteen independent Pc-to-pc mutations were
      analyzed, and each was found to remove all or part of the central gene of the
      threesome. Hence, this central gene is Pc. Most Pc-to-pc mutations were
      associated with unequal recombination. Eight recombination events were localized
      to different sites in a 560-bp region within the approximately 3.7-kb NBS-LRR
      genes. Because any unequal recombination located within the flanking NBS-LRR
      genes would have removed Pc, the clustering of cross-over events within a 560-bp
      segment indicates that a site-directed recombination process exists that
      specifically targets unequal events to generate LRR diversity in NBS-LRR loci.

PMID- 18719094
TI  - TRPV4 channel participates in receptor-operated calcium entry and ciliary beat
      frequency regulation in mouse airway epithelial cells.
AB  - The rate of mucociliary clearance in the airways is a function of ciliary beat
      frequency (CBF), and this, in turn, is increased by increases in intracellular
      calcium. The TRPV4 cation channel mediates Ca(2+) influx in response to
      mechanical and osmotic stimuli in ciliated epithelia. With the use of a TRPV4
      deficient mouse, we now show that TRPV4 is involved in the airways' response to
      physiologically relevant physical and chemical stimuli. Ciliary TRPV4 expression
      in tracheal epithelial cells was confirmed with immunofluorescence in TRPV4(+/+)
      mice. Ciliated tracheal cells from TRPV4(-/-) mice showed no increases in
      intracellular Ca(2+) and CBF in response to the synthetic activator 4alpha
      phorbol 12,13-didecanoate (4alphaPDD) and reduced responses to mild temperature,
      another TRPV4-activating stimulus. Autoregulation of CBF in response to high
      viscosity solutions is preserved in TRPV4(-/-) despite a reduced Ca(2+) signal.
      More interestingly, TRPV4 contributed to an ATP-induced increase in CBF,
      providing a pathway for receptor-operated Ca(2+) entry but not store-operated
      Ca(2+) entry as the former mechanism is lost in TRPV4(-/-) cells. Collectively,
      these results suggest that TRPV4 is predominantly located in the cilia of
      tracheal epithelial cells and plays a key role in the transduction of physical
      and chemical stimuli into a Ca(2+) signal that regulates CBF and mucociliary
      transport. Moreover, these studies implicate the participation of TRPV4 in
      receptor-operated Ca(2+) entry.

PMID- 18719095
TI  - An engineered selenocysteine defines a unique class of antibody derivatives.
AB  - Selenocysteine is cotranslationally inserted into proteins by recoding the stop
      codon UGA from termination to selenocysteine insertion. The nucleophilic selenol
      group of selenocysteine endows this rare amino acid with unique chemical
      reactivity that allows regiospecific covalent conjugation in the presence of the
      other natural amino acids. Using a mammalian expression system, we generated an
      IgG1-derived Fc fragment with a C-terminal selenocysteine in yields comparable to
      conventional monoclonal antibodies and conjugated it to an electrophilic
      derivative of a peptidomimetic that binds with high affinity and specificity to
      integrin alpha(4)beta(1). Through this conjugation, both the biological and
      chemical components are endowed with pharmacological advantages. We demonstrate
      that whereas the Fc protein increases the circulatory half-life from minutes to
      days and mediates transcytosis through binding to the neonatal Fc receptor, the
      peptidomimetic introduces cross-species binding to cell surface integrin
      alpha(4)beta(1) and blocks its interaction with vascular cell adhesion molecule
      1. Compared with conventional monoclonal antibodies, our technology benefits
      economically from combining a generic biological component with a variable
      chemical component.

PMID- 18719096
TI  - Brk is coamplified with ErbB2 to promote proliferation in breast cancer.
AB  - Amplification of the receptor tyrosine kinase ErbB2 is frequently observed in
      breast cancer. Amplification of erbB2 is also associated with multiple genomic
      gains and losses; however, the importance of these associated changes is largely
      unknown. We demonstrate that Brk, a cytoplasmic tyrosine kinase, is coamplified
      and coexpressed with ErbB2 in human breast cancers. ErbB2 interacts with Brk and
      increases its intrinsic kinase activity. Expression of Brk enhances the ErbB2
      induced activation of Ras/MAPK signaling and cyclin E/cdk2 activity to induce
      cell proliferation of mammary 3-dimensional acini in culture. In a murine model
      of breast cancer, expression of Brk was found to shorten the latency of ErbB2
      induced tumors by promoting cell proliferation, with no effect on protection from
      apoptosis. Furthermore, overexpression of Brk conferred resistance to the ability
      of Lapatinib, an ErbB2 kinase inhibitor, to inhibit ErbB2-induced proliferation.
      Thus, we identified Brk as a drug target for ErbB2-positive cancers.

PMID- 18719097
TI  - Resolving voltage-dependent structural changes of a membrane photoreceptor by
      surface-enhanced IR difference spectroscopy.
AB  - Membrane proteins are molecular machines that transport ions, solutes, or
      information across the cell membrane. Electrophysiological techniques have
      unraveled many functional aspects of ion channels but suffer from the lack of
      structural sensitivity. Here, we present spectroelectrochemical data on
      vibrational changes of membrane proteins derived from a single monolayer. For the
      seven-helical transmembrane protein sensory rhodopsin II, structural changes of
      the protein backbone and the retinal cofactor as well as single ion transfer
      events are resolved by surface-enhanced IR difference absorption spectroscopy
      (SEIDAS). Angular changes of bonds versus the membrane normal have been
      determined because SEIDAS monitors only those vibrations whose dipole moment are
      oriented perpendicular to the solid surface. The application of negative membrane
      potentials (DeltaV = -0.3 V) leads to the selective halt of the light-induced
      proton transfer at the stage of D75, the counter ion of the retinal Schiff base.
      It is inferred that the voltage raises the energy barrier of this particular
      proton-transfer reaction, rendering the energy deposited in the retinal by light
      excitation insufficient for charge transfer to occur. The other structural
      rearrangements that accompany light-induced activity of the membrane protein, are
      essentially unaffected by the transmembrane electric field. Our results
      demonstrate that SEIDAS is a generic approach to study processes that depend on
      the membrane potential, like those in voltage-gated ion channels and
      transporters, to elucidate the mechanism of ion transfer with unprecedented
      spatial sensitivity and temporal resolution.

PMID- 18719098
TI  - The Kv channel blocker 4-aminopyridine enhances Ag+ uptake: a scanning
      electrochemical microscopy study of single living cells.
AB  - We report that silver ion (Ag(+)) uptake is enhanced by 4-aminopyridine (4-AP), a
      well known voltage-sensitive potassium ion channel (K(v)) blocker. Both bacterial
      (Escherichia coli) and mammalian (3T3 fibroblast) cells were used as model
      systems. Ag(+) uptake was monitored with a scanning electrochemical microscope
      with an amperometric Ag(+) ion-selective electrode (Ag(+)-ISE) and the
      respiration rates of E. coli cells were measured by oxygen reduction at an
      ultramicroelectrode. The results showed that not only the amount but also the
      rate of silver uptake by the cells increased significantly when 4-AP was added to
      the solution. For fibroblasts, the Ag(+) uptake rate was 4.8 x 10(7) ions per
      cell per sec without 4-AP compared with 1.0 x 10(8) ions per cell per sec with
      0.2 mM 4-AP. For E. coli cells, the uptake rate was 1.5 x 10(4) ions per cell per
      sec without 4-AP vs. 3.5 x 10(4) ions per cell per sec with 0.5 mM 4-AP and 5.9 x
      10(4) ions per cell per sec with 1 mM 4-AP. Thus, 4-AP might be useful where
      silver is used as antimicrobial agent to speed its uptake.

PMID- 18719099
TI  - Object continuity enhances selective auditory attention.
AB  - In complex scenes, the identity of an auditory object can build up across
      seconds. Given that attention operates on perceptual objects, this perceptual
      buildup may alter the efficacy of selective auditory attention over time. Here,
      we measured identification of a sequence of spoken target digits presented with
      distracter digits from other directions to investigate the dynamics of selective
      attention. Performance was better when the target location was fixed rather than
      changing between digits, even when listeners were cued as much as 1 s in advance
      about the position of each subsequent digit. Spatial continuity not only avoided
      well known costs associated with switching the focus of spatial attention, but
      also produced refinements in the spatial selectivity of attention across time.
      Continuity of target voice further enhanced this buildup of selective attention.
      Results suggest that when attention is sustained on one auditory object within a
      complex scene, attentional selectivity improves over time. Similar effects may
      come into play when attention is sustained on an object in a complex visual
      scene, especially in cases where visual object formation requires sustained
      attention.

PMID- 18719100
TI  - Transcriptional profiling of endogenous germ layer precursor cells identifies
      dusp4 as an essential gene in zebrafish endoderm specification.
AB  - A major goal for developmental biologists is to define the behaviors and
      molecular contents of differentiating cells. We have devised a strategy for
      isolating cells from diverse embryonic regions and stages in the zebrafish, using
      computer-guided laser photoconversion of injected Kaede protein and flow
      cytometry. This strategy enabled us to perform a genome-wide transcriptome
      comparison of germ layer precursor cells. Mesendoderm and ectoderm precursors
      cells isolated by this method differentiated appropriately in transplantation
      assays. Microarray analysis of these cells reidentified known genes at least as
      efficiently as previously reported strategies that relied on artificial
      mesendoderm activation or inhibition. We also identified a large set of
      uncharacterized mesendoderm-enriched genes as well as ectoderm-enriched genes.
      Loss-of-function studies revealed that one of these genes, the MAP kinase
      inhibitor dusp4, is essential for early development. Embryos injected with
      antisense morpholino oligonucleotides that targeted Dusp4 displayed necrosis of
      head tissues. Marker analysis during late gastrulation revealed a specific loss
      of sox17, but not of other endoderm markers, and analysis at later stages
      revealed a loss of foregut and pancreatic endoderm. This specific loss of sox17
      establishes a new class of endoderm specification defect.

PMID- 18719101
TI  - Highly efficient differentiation of hESCs to functional hepatic endoderm requires
      ActivinA and Wnt3a signaling.
AB  - Human embryonic stem cells (hESCs) are a valuable source of pluripotential
      primary cells. To date, however, their homogeneous cellular differentiation to
      specific cell types in vitro has proven difficult. Wnt signaling has been shown
      to play important roles in coordinating development, and we demonstrate that
      Wnt3a is differentially expressed at critical stages of human liver development
      in vivo. The essential role of Wnt3a in hepatocyte differentiation from hESCs is
      paralleled by our in vitro model, demonstrating the importance of a physiologic
      approach to cellular differentiation. Our studies provide compelling evidence
      that Wnt3a signaling is important for coordinated hepatocellular function in
      vitro and in vivo. In addition, we demonstrate that Wnt3a facilitates clonal
      plating of hESCs exhibiting functional hepatic differentiation. These studies
      represent an important step toward the use of hESC-derived hepatocytes in high
      throughput metabolic analysis of human liver function.

PMID- 18719102
TI  - Netrin-4 inhibits angiogenesis via binding to neogenin and recruitment of Unc5B.
AB  - Netrins are secreted molecules with roles in axon guidance and angiogenesis. We
      identified Netrin-4 as a gene specifically overexpressed in VEGF-stimulated
      endothelial cells (EC) in vitro as well as in vivo. Knockdown of Netrin-4
      expression in EC increased their ability to form tubular structures on Matrigel.
      To identify which receptor is involved, we showed by quantitative RT-PCR that EC
      express three of the six Netrin-1 cognate receptors: neogenin, Unc5B, and Unc5C.
      In contrast to Netrin-1, Netrin-4 bound only to neogenin but not to Unc5B or
      Unc5C receptors. Neutralization of Netrin-4 binding to neogenin by blocking
      antibodies abolished the chemotactic effect of Netrin-4. Furthermore, the
      silencing of either neogenin or Unc5B abolished Netrin-4 inhibitory effect on EC
      migration, suggesting that both receptors are essential for its function in
      vitro. Coimmunoprecipitation experiments demonstrated that Netrin-4 increased the
      association between Unc5B and neogenin on VEGF- or FGF-2-stimulated EC. Finally,
      we showed that Netrin-4 significantly reduced pathological angiogenesis in
      Matrigel and laser-induced choroidal neovascularization models. Interestingly,
      Netrin-4, neogenin, and Unc5B receptor expression was up-regulated in choroidal
      neovessel EC after laser injury. Moreover, Netrin-4 overexpression delayed tumor
      angiogenesis in a model of s.c. xenograft. We propose that Netrin-4 acts as an
      antiangiogenic factor through binding to neogenin and recruitment of Unc5B.

PMID- 18719103
TI  - Late-surviving megafauna in Tasmania, Australia, implicate human involvement in
      their extinction.
AB  - Establishing the cause of past extinctions is critical if we are to understand
      better what might trigger future occurrences and how to prevent them. The
      mechanisms of continental late Pleistocene megafaunal extinction, however, are
      still fiercely contested. Potential factors contributing to their demise include
      climatic change, human impact, or some combination. On the Australian mainland,
      90% of the megafauna became extinct by approximately 46 thousand years (ka) ago,
      soon after the first archaeological evidence for human colonization of the
      continent. Yet, on the neighboring island of Tasmania (which was connected to the
      mainland when sea levels were lower), megafaunal extinction appears to have taken
      place before the initial human arrival between 43 and 40 ka, which would seem to
      exonerate people as a contributing factor in the extirpation of the island
      megafauna. Age estimates for the last megafauna, however, are poorly constrained.
      Here, we show, by direct dating of fossil remains and their associated sediments,
      that some Tasmanian megafauna survived until at least 41 ka (i.e., after their
      extinction on the Australian mainland) and thus overlapped with humans.
      Furthermore, a vegetation record for Tasmania spanning the last 130 ka shows that
      no significant regional climatic or environmental change occurred between 43 and
      37 ka, when a land bridge existed between Tasmania and the mainland. Our results
      are consistent with a model of human-induced extinction for the Tasmanian
      megafauna, most probably driven by hunting, and they reaffirm the value of
      islands adjacent to continental landmasses as tests of competing hypotheses for
      late Quaternary megafaunal extinctions.

PMID- 18719104
TI  - Molecular basis for the autoregulation of the protein acetyl transferase Rtt109.
AB  - Rtt109 is a protein acetyltransferase (PAT) that is responsible for the
      acetylation of lysine-56 of histone 3 (H3K56) in yeast. H3K56 acetylation has
      been implicated in the weakening of the interaction between the histone core and
      the surrounding DNA in the nucleosomal particle. Rtt109, in cooperation with
      various histone chaperones, promotes genomic stability and is required for
      resistance to DNA damaging agents. Here, we present the crystal structure of
      Rtt109 in complex with acetyl-CoA at a 2.0-A resolution. Rtt109 consists of a
      core PAT domain, which binds the acetyl-CoA cofactor. A second domain, the
      activation domain, is tightly associated with the PAT domain. Autoacetylation of
      lysine-290 within the activation domain is required for stabilizing the
      interaction between the two domains and is essential for catalysis. Biochemical
      analysis demonstrates the requirement of a loop within the PAT domain for the
      binding of the histone chaperone Vps75, and mutational analysis identifies key
      residues for catalysis. We propose a model in which the autoacetylation of Rtt109
      is crucial for the regulation of its catalytic activity.

PMID- 18719105
TI  - Erythromycin derivatives inhibit HIV-1 replication in macrophages through
      modulation of MAPK activity to induce small isoforms of C/EBPbeta.
AB  - Macrophages (MPhis) are a major source of HIV-1 especially in patients with
      tuberculosis. There are MPhis that are permissive and those that restrict HIV-1.
      Regulation of hematopoietic cell kinase (Hck) activity and selective expression
      of CCAAT enhancer binding protein beta (C/EBPbeta) isoforms greatly contribute to
      determine distinct susceptibility of MPhis to HIV-1. Resistance is attributable
      to reduced expression of Hck and augmented expression of an inhibitory small
      isoform of C/EBPbeta. Derivatives of erythromycin A (EMA) EM201 and EM703 inhibit
      the replication of HIV-1 in tissue MPhis, at posttranscriptional and
      translational levels. We demonstrate that EM201 and EM703 convert tissue MPhis
      from HIV-1 susceptible to HIV-1 resistant through down-regulation of Hck and
      induction of small isoforms of C/EBPbeta. These drugs inhibit p38MAPK activation
      which is expressed only in susceptible tissue MPhis. Activated CD4(+)T cells
      stimulate the viral replication in HIV-1 resistant MPhis through down-regulation
      of small isoforms of C/EBPbeta via activation of ERK1/2. EM201 and EM703 can
      inhibit the MAPK activation and inhibit the burst of viral replication produced
      when CD4(+)T cells and MPhis interact. These EM derivatives may be highly
      beneficial for repression of residual HIV-1 in the lymphoreticular system of HIV
      1-infected patients and offer great promise for the creation of new anti-HIV
      drugs for the future treatment of AIDS patients.

PMID- 18719106
TI  - Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH
      prevents genomic instability from stalled replication forks.
AB  - Chronic stalling of DNA replication forks caused by DNA damage can lead to
      genomic instability. Cells have evolved lesion bypass pathways such as
      postreplication repair (PRR) to resolve these arrested forks. In yeast, one
      branch of PRR involves proliferating cell nuclear antigen (PCNA)
      polyubiquitination mediated by the Rad5-Ubc13-Mms2 complex that allows bypass of
      DNA lesion by a template-switching mechanism. Previously, we identified human
      SHPRH as a functional homologue of yeast Rad5 and revealed the existence of RAD5
      like pathway in human cells. Here we report the identification of HLTF as a
      second RAD5 homologue in human cells. HLTF, like SHPRH, shares a unique domain
      architecture with Rad5 and promotes lysine 63-linked polyubiquitination of PCNA.
      Similar to yeast Rad5, HLTF is able to interact with UBC13 and PCNA, as well as
      SHPRH; and the reduction of either SHPRH or HLTF expression enhances spontaneous
      mutagenesis. Moreover, Hltf-deficient mouse embryonic fibroblasts show elevated
      chromosome breaks and fusions after methyl methane sulfonate treatment. Our
      results suggest that HLTF and SHPRH are functional homologues of yeast Rad5 that
      cooperatively mediate PCNA polyubiquitination and maintain genomic stability.

PMID- 18719107
TI  - Molecular identification of a major quantitative trait locus, qLTG3-1,
      controlling low-temperature germinability in rice.
AB  - Tolerance to abiotic stress is an important agronomic trait in crops and is
      controlled by many genes, which are called quantitative trait loci (QTLs).
      Identification of these QTLs will contribute not only to the understanding of
      plant biology but also for plant breeding, to achieve stable crop production
      around the world. Previously, we mapped three QTLs controlling low-temperature
      tolerance at the germination stage (called low-temperature germinability). To
      understand the molecular basis of one of these QTLs, qLTG3-1 (quantitative trait
      locus for low-temperature germinability on chromosome 3), map-based cloning was
      performed, and this QTL was shown to be encoded by a protein of unknown function.
      The QTL qLTG3-1 is strongly expressed in the embryo during seed germination.
      Before and during seed germination, specific localization of beta-glucuronidase
      staining in the tissues covering the embryo, which involved the epiblast covering
      the coleoptile and the aleurone layer of the seed coat, was observed. Expression
      of qLTG3-1 was tightly associated with vacuolation of the tissues covering the
      embryo. This may cause tissue weakening, resulting in reduction of the mechanical
      resistance to the growth potential of the coleoptile. These phenomena are quite
      similar to the model system of seed germination presented by dicot plants,
      suggesting that this model may be conserved in both dicot and monocot plants.

PMID- 18719108
TI  - Molecular basis of the interaction between the antiapoptotic Bcl-2 family
      proteins and the proapoptotic protein ASPP2.
AB  - We have characterized the molecular basis of the interaction between ASPP2 and
      Bcl-2, which are key proteins in the apoptotic pathway. The C-terminal ankyrin
      repeats and SH3 domain of ASPP2 (ASPP2(Ank-SH3)) mediate its interactions with
      the antiapoptotic protein Bcl-2. We used biophysical and computational methods to
      identify the interaction sites of Bcl-2 and its homologues with ASPP2. Using
      peptide array screening, we found that ASPP2(Ank-SH3) binds two homologous sites
      in all three Bcl proteins tested: (i) the conserved BH4 motif, and (ii) a binding
      site for proapoptotic regulators. Quantitative binding studies revealed that
      binding of ASPP2(Ank-SH3) to the Bcl-2 family members is selective at two levels:
      (i) interaction with Bcl-2-derived peptides is the tightest compared to peptides
      from the other family members, and (ii) within Bcl-2, binding of ASPP2(Ank-SH3)
      to the BH4 domain is tightest. Sequence alignment of the ASPP2-binding peptides
      combined with binding studies of mutated peptides revealed that two nonconserved
      positions where only Bcl-2 contains positively charged residues account for its
      tighter binding. The experimental binding results served as a basis for docking
      analysis, by which we modeled the complexes of ASPP2(Ank-SH3) with the full
      length Bcl proteins. Using peptide arrays and quantitative binding studies, we
      found that Bcl-2 binds three loops in ASPP2(Ank-SH3) with similar affinity, in
      agreement with our predicted model. Based on our results, we propose a mechanism
      in which ASPP2 induces apoptosis by inhibiting functional sites of the
      antiapoptotic Bcl-2 proteins.

PMID- 18719109
TI  - Methionine oxidation impairs reverse cholesterol transport by apolipoprotein A-I.
AB  - HDL protects against vascular disease by accepting free cholesterol from
      macrophage foam cells in the artery wall. This pathway is critically dependent on
      lecithin:cholesterol acyltransferase (LCAT), which rapidly converts cholesterol
      to cholesteryl ester. The physiological activator of LCAT is apolipoprotein A-I
      (apoA-I), the major HDL protein. However, cholesterol removal is compromised if
      apoA-I is exposed to reactive intermediates. In humans with established
      cardiovascular disease, myeloperoxidase (MPO) oxidizes HDL, and oxidation by MPO
      impairs apoA-I's ability to activate LCAT in vitro. Because a single methionine
      residue in apoA-I, Met-148, resides near the center of the protein's LCAT
      activation domain, we determined whether its oxidation by MPO could account for
      the loss of LCAT activity. Mass spectrometric analysis demonstrated that
      oxidation of Met-148 to methionine sulfoxide associated quantitatively with loss
      of LCAT activity in both discoidal HDL and HDL(3), the enzyme's physiological
      substrates. Reversing oxidation with methionine sulfoxide reductase restored
      HDL's ability to activate LCAT. Discoidal HDL prepared with apoA-I containing a
      Met-148-->Leu mutation was significantly resistant to inactivation by MPO. Based
      on structural data in the literature, we propose that oxidation of Met-148
      disrupts apoA-I's central loop, which overlaps the LCAT activation domain. These
      observations implicate oxidation of a single Met in apoA-I in impaired LCAT
      activation, a critical early step in reverse cholesterol transport.

PMID- 18719110
TI  - In vivo studies fail to reveal a role for IL-4 or STAT6 signaling in Th2
      lymphocyte differentiation.
AB  - The expression of interleukin-4 (IL-4) is viewed as the hallmark of a Th2
      lymphocyte, whereas the subsequent action of IL-4 and IL-13, mediated through the
      STAT6 signaling pathway, is seen as a prerequisite for the full development of
      Th2 immune responses to parasites and allergens. G4 mice, whose IL-4 gene locus
      contains the fluorescent reporter eGFP, were used to quantify the number of Th2
      cells that develop during Nippostrongylus brasiliensis- or allergen-induced
      immune responses under conditions where IL-4 or STAT6 was absent. Here, we show
      that deletion of IL-4 or STAT6 had little impact on the number or timing of
      appearance of IL-4-producing Th2 cells. These data indicate that in vivo
      differentiation of naive CD4 T cells to Th2 status often occurs independently of
      IL-4 and STAT6 and that recently described pathways of Th2 cell differentiation
      may explain how allergens and parasites selectively induce Th2-mediated immunity.

PMID- 18719111
TI  - Potential landscape and flux framework of nonequilibrium networks: robustness,
      dissipation, and coherence of biochemical oscillations.
AB  - We established a theoretical framework for studying nonequilibrium networks with
      two distinct natures essential for characterizing the global probabilistic
      dynamics: the underlying potential landscape and the corresponding curl flux. We
      applied the idea to a biochemical oscillation network and found that the
      underlying potential landscape for the oscillation limit cycle has a distinct
      closed ring valley (Mexican hat-like) shape when the fluctuations are small. This
      global landscape structure leads to attractions of the system to the ring valley.
      On the ring, we found that the nonequilibrium flux is the driving force for
      oscillations. Therefore, both structured landscape and flux are needed to
      guarantee a robust oscillating network. The barrier height separating the
      oscillation ring and other areas derived from the landscape topography is shown
      to be correlated with the escaping time from the limit cycle attractor and
      provides a quantitative measure of the robustness for the network. The landscape
      becomes shallower and the closed ring valley shape structure becomes weaker
      (lower barrier height) with larger fluctuations. We observe that the period and
      the amplitude of the oscillations are more dispersed and oscillations become less
      coherent when the fluctuations increase. We also found that the entropy
      production of the whole network, characterizing the dissipation costs from the
      combined effects of both landscapes and fluxes, decreases when the fluctuations
      decrease. Therefore, less dissipation leads to more robust networks. Our approach
      is quite general and applicable to other networks, dynamical systems, and
      biological evolution. It can help in designing robust networks.

PMID- 18719112
TI  - Information flow and optimization in transcriptional regulation.
AB  - In the simplest view of transcriptional regulation, the expression of a gene is
      turned on or off by changes in the concentration of a transcription factor (TF).
      We use recent data on noise levels in gene expression to show that it should be
      possible to transmit much more than just one regulatory bit. Realizing this
      optimal information capacity would require that the dynamic range of TF
      concentrations used by the cell, the input/output relation of the regulatory
      module, and the noise in gene expression satisfy certain matching relations,
      which we derive. These results provide parameter-free, quantitative predictions
      connecting independently measurable quantities. Although we have considered only
      the simplified problem of a single gene responding to a single TF, we find that
      these predictions are in surprisingly good agreement with recent experiments on
      the Bicoid/Hunchback system in the early Drosophila embryo and that this system
      achieves approximately 90% of its theoretical maximum information transmission.

PMID- 18719113
TI  - Alfalfa benefits from Medicago truncatula: the RCT1 gene from M. truncatula
      confers broad-spectrum resistance to anthracnose in alfalfa.
AB  - Alfalfa is economically the most important forage legume worldwide. A recurrent
      challenge to alfalfa production is the significant yield loss caused by disease.
      Although knowledge of molecular mechanisms underlying host resistance should
      facilitate the genetic improvement of alfalfa, the acquisition of such knowledge
      is hampered by alfalfa's tetrasomic inheritance and outcrossing nature. However,
      alfalfa is congeneric with the reference legume Medicago truncatula, providing an
      opportunity to use M. truncatula as a surrogate to clone the counterparts of many
      agronomically important genes in alfalfa. In particular, the high degree of
      sequence identity and remarkably conserved genome structure and function between
      the two species enables M. truncatula genes to be used directly in alfalfa
      improvement. Here we report the map-based cloning of RCT1, a host resistance (R)
      gene in M. truncatula that confers resistance to multiple races of Colletotrichum
      trifolii, a hemibiotrophic fungal pathogen that causes anthracnose disease of
      alfalfa. RCT1 is a member of the Toll-interleukin-1 receptor/nucleotide-binding
      site/leucine-rich repeat (TIR-NBS-LRR) class of plant R genes and confers broad
      spectrum anthracnose resistance when transferred into susceptible alfalfa plants.
      Thus, RCT1 provides a novel resource to develop anthracnose-resistant alfalfa
      cultivars and contributes to our understanding of host resistance against the
      fungal genus Colletotrichum. This work demonstrates the potential of using M.
      truncatula genes for genetic improvement of alfalfa.

PMID- 18719114
TI  - Nucleus accumbens AGS3 expression drives ethanol seeking through G betagamma.
AB  - Approximately 90% of alcoholics relapse within 4 years, in part because of an
      enhanced motivation to seek alcohol (EtOH). A novel G protein modulator
      (Gpsm1/AGS3) was up-regulated in the rat nucleus accumbens core (NAcore) but not
      in other limbic nuclei during abstinence from operant EtOH self-administration.
      Furthermore, NAcore AGS3 knockdown reduced EtOH seeking to pre-abstinence levels
      in a novel rat model of compulsive, human EtOH seeking. AGS3 can both inhibit G
      protein G i alpha-mediated signaling and stimulate G betagamma-mediated
      signaling. Accordingly, sequestration of G betagamma, but not G i alpha
      knockdown, significantly reduced EtOH seeking to pre-abstinence levels. Thus,
      AGS3 and G betagamma are hypothesized to gate the uncontrolled motivation to seek
      EtOH during abstinence. AGS3 up-regulation during abstinence may be a key
      determinant of the transition from social consumption to compulsion-like seeking
      during relapse.

PMID- 18719115
TI  - The H19 locus acts in vivo as a tumor suppressor.
AB  - The H19 locus belongs to a cluster of imprinted genes that is linked to the human
      Beckwith-Wiedemann syndrome. The expression of H19 and its closely associated
      IGF2 gene is frequently deregulated in some human tumors, such as Wilms' tumors.
      In these cases, biallelic IGF2 expression and lack of expression of H19 are
      associated with hypermethylation of the imprinting center of this locus. These
      observations and others have suggested a potential tumor suppressor effect of the
      H19 locus. Some studies have also suggested that H19 is an oncogene, based on
      tissue culture systems. We show, using in vivo murine models of tumorigenesis,
      that the H19 locus controls the size of experimental teratocarcinomas, the number
      of polyps in the Apc murine model of colorectal cancer and the timing of
      appearance of SV40-induced hepatocarcinomas. The H19 locus thus clearly displays
      a tumor suppressor effect in mice.

PMID- 18719116
TI  - Opposing plant community responses to warming with and without herbivores.
AB  - If controls over primary productivity and plant community composition are mainly
      environmental, as opposed to biological, then global change may result in large
      scale alterations in ecosystem structure and function. This view appears to be
      favored among investigations of plant biomass and community responses to
      experimental and observed warming. In far northern and arctic ecosystems, such
      studies predict increasing dominance of woody shrubs with future warming and
      emphasize the carbon (C)-sequestration potential and consequent atmospheric
      feedback potential of such responses. In contrast to previous studies, we
      incorporated natural herbivory by muskoxen and caribou into a 5-year experimental
      investigation of arctic plant community response to warming. In accordance with
      other studies, warming increased total community biomass by promoting growth of
      deciduous shrubs (dwarf birch and gray willow). However, muskoxen and caribou
      reduced total community biomass response, and responses of birch and willow, to
      warming by 19%, 46%, and 11%, respectively. Furthermore, under warming alone, the
      plant community shifted after 5 years away from graminoid-dominated toward dwarf
      birch-dominated. In contrast, where herbivores grazed, plant community
      composition on warmed plots did not differ from that on ambient plots after 5
      years. These results highlight the potentially important and overlooked
      influences of vertebrate herbivores on plant community response to warming and
      emphasize that conservation and management of large herbivores may be an
      important component of mitigating ecosystem response to climate change.

PMID- 18719117
TI  - Interaction between connexin35 and zonula occludens-1 and its potential role in
      the regulation of electrical synapses.
AB  - Although regulation of chemical transmission is known to involve the interaction
      of receptors with scaffold proteins, little is known about the existence of
      protein-protein interactions in regulating gap junction-mediated electrical
      synapses. The scaffold protein zonula-occludens-1 (ZO-1), a member of the MAGUK
      family of proteins, was reported to interact with several connexins (Cxs). We
      show here that ZO-1 extensively colocalizes with Cx35 at identifiable "mixed"
      (electrical and chemical) contacts on goldfish Mauthner cells, a model synapse
      for the study of vertebrate electrical transmission where it is possible to
      correlate physiological properties with molecular composition. Further, our
      analysis indicates that these proteins directly interact at goldfish electrical
      synapses. In contrast to Cx43, which interacts with ZO-1 via the PDZ2 domain,
      Cx35 interacts with ZO-1 via the PDZ1 domain, and this association is of lower
      affinity. The properties of the ZO-1/Cx35 association suggest the existence of a
      more dynamic relation between these two proteins, possibly including a role of ZO
      1 in regulating gap junctional conductance at these highly modifiable electrical
      synapses. The interaction of ZO-1 with conserved regions of the C termini of
      Cx35/Cx36 orthologs may have a common function at electrical synapses of mammals
      and other vertebrates.

PMID- 18719118
TI  - Mutant dynein (Loa) triggers proprioceptive axon loss that extends survival only
      in the SOD1 ALS model with highest motor neuron death.
AB  - Dominant mutations in cytoplasmic dynein (Loa or Cra) have been reported to
      provoke selective, age-dependent killing of motor neurons, while paradoxically
      slowing degeneration and death of motor neurons in one mouse model of an
      inherited form of ALS. Examination of Loa animals reveals no degeneration of
      large caliber alpha-motor neurons beyond an age-dependent loss (initiating only
      after 18 months) that was comparable in Loa and wild-type littermates. Absence of
      Loa-mediated alpha-motor neuron loss contrasted with dramatic, sustained, mutant
      dynein-mediated postnatal loss of lumbar proprioceptive sensory axons,
      accompanied by decreased excitatory glutamatergic inputs to motor neurons. In
      mouse models of inherited ALS caused by mutations in superoxide dismutase (SOD1),
      mutant dynein modestly prolonged survival in the one mouse model with the most
      extensive motor neuron loss (SOD(G93A)) while showing marginal (SOD(G85R)) or no
      (SOD(G37R)) benefit in models with higher numbers of surviving motor neurons at
      end stage. These findings support a noncell autonomous, excitotoxic contribution
      from proprioceptive sensory neurons that modestly accelerates disease onset in
      inherited ALS.

PMID- 18719119
TI  - Transmembrane domain length of viral K+ channels is a signal for mitochondria
      targeting.
AB  - K(+) channels operate in the plasma membrane and in membranes of organelles
      including mitochondria. The mechanisms and topogenic information for their
      differential synthesis and targeting is unknown. This article describes 2 similar
      viral K(+) channels that are differentially sorted; one protein (Kesv) is
      imported by the Tom complex into the mitochondria, the other (Kcv) to the plasma
      membrane. By creating chimeras we discovered that mitochondrial sorting of Kesv
      depends on a hierarchical combination of N- and C-terminal signals. Crucial is
      the length of the second transmembrane domain; extending its C terminus by > or =
      2 hydrophobic amino acids redirects Kesv from the mitochondrial to the plasma
      membrane. Activity of Kesv in the plasma membrane is detected electrically or by
      yeast rescue assays only after this shift in sorting. Hence only minor structural
      alterations in a transmembrane domain are sufficient to switch sorting of a K(+)
      channel between the plasma membrane and mitochondria.

PMID- 18719121
TI  - Beyond tumor necrosis factor receptor: TRADD signaling in toll-like receptors.
AB  - Tumor necrosis factor receptor 1-associated death domain protein (TRADD) is the
      core adaptor recruited to TNF receptor 1 (TNFR1) upon TNFalpha stimulation. In
      cells from TRADD-deficient mice, TNFalpha-mediated apoptosis and TNFalpha
      stimulated NF-kappaB, JNK, and ERK activation are defective. TRADD is also
      important for germinal center formation, DR3-mediated costimulation of T cells,
      and TNFalpha-mediated inflammatory responses in vivo. TRADD deficiency does not
      enhance IFNgamma-induced signaling. Importantly, TRADD has a novel role in TLR3
      and TLR4 signaling. TRADD participates in the TLR4 complex formed upon LPS
      stimulation, and TRADD-deficient macrophages show impaired cytokine production in
      response to TLR ligands in vitro. Thus, TRADD is a multifunctional protein
      crucial both for TNFR1 signaling and other signaling pathways relevant to immune
      responses.

PMID- 18719120
TI  - Engineering graded tissue interfaces.
AB  - Interfacial zones between tissues provide specialized, transitional junctions
      central to normal tissue function. Regenerative medicine strategies focused on
      multiple cell types and/or bi/tri-layered scaffolds do not provide continuously
      graded interfaces, severely limiting the integration and biological performance
      of engineered tissue substitutes. Inspired by the bone-soft tissue interface, we
      describe a biomaterial-mediated gene transfer strategy for spatially regulated
      genetic modification and differentiation of primary dermal fibroblasts within
      tissue-engineered constructs. We demonstrate that zonal organization of
      osteoblastic and fibroblastic cellular phenotypes can be engineered by a simple,
      one-step seeding of fibroblasts onto scaffolds containing a spatial distribution
      of retrovirus encoding the osteogenic transcription factor Runx2/Cbfa1. Gradients
      of immobilized retrovirus, achieved via deposition of controlled poly(L-lysine)
      densities, resulted in spatial patterns of transcription factor expression,
      osteoblastic differentiation, and mineralized matrix deposition. Notably, this
      graded distribution of mineral deposition and mechanical properties was
      maintained when implanted in vivo in an ectopic site. Development of this facile
      and robust strategy is significant toward the regeneration of continuous
      interfacial zones that mimic the cellular and microstructural characteristics of
      native tissue.

PMID- 18719122
TI  - Mass spectrometry-based discovery of circadian peptides.
AB  - A significant challenge to understanding dynamic and heterogeneous brain systems
      lies in the chemical complexity of secreted intercellular messengers that change
      rapidly with space and time. Two solid-phase extraction collection strategies are
      presented that relate time and location of peptide release with mass
      spectrometric characterization. Here, complex suites of peptide-based cell-to
      cell signaling molecules are characterized from the mammalian suprachiasmatic
      nucleus (SCN), site of the master circadian clock. Observed SCN releasates are
      peptide rich and demonstrate the co-release of established circadian
      neuropeptides and peptides with unknown roles in circadian rhythms. Additionally,
      the content of SCN releasate is stimulation specific. Stimulation paradigms
      reported to alter clock timing, including electrical stimulation of the
      retinohypothalamic tract, produce releasate mass spectra that are notably
      different from the spectra of compounds secreted endogenously over the course of
      the 24-h cycle. In addition to established SCN peptides, we report the presence
      of proSAAS peptides in releasates. One of these peptides, little SAAS, exhibits
      robust retinohypothalamic tract-stimulated release from the SCN, and exogenous
      application of little SAAS induces a phase delay consistent with light-mediated
      cues regulating circadian timing. These mass spectrometry-based analyses provide
      a new perspective on peptidergic signaling within the SCN and demonstrate that
      the integration of secreted compounds with information relating time and location
      of release generates new insights into intercellular signaling in the brain.

PMID- 18719123
TI  - Localizing organomercury uptake and accumulation in zebrafish larvae at the
      tissue and cellular level.
AB  - Using synchrotron x-ray fluorescence mapping, we have examined the uptake and
      localization of organic mercury in zebrafish larvae. Strikingly, the greatest
      accumulation of methyl and ethyl mercury compounds was highly localized in the
      rapidly dividing lens epithelium, with lower levels going to brain, optic nerve,
      and various other organs. The data suggest that the reported impairment of visual
      processes by mercury may arise not only from previously reported neurological
      effects, but also from direct effects on the ocular tissue. This novel approach
      is a powerful tool for directly investigating the molecular toxicology of heavy
      metals, and should be equally applicable to the study of a wide range of elements
      in developing embryos.

PMID- 18719124
TI  - Stress resistance and signal fidelity independent of nuclear MAPK function.
AB  - Elevated external solute stimulates a conserved MAPK cascade that elicits
      responses that maintain osmotic balance. The yeast high-osmolarity glycerol (HOG)
      pathway activates Hog1 MAPK (mammalian ortholog p38alpha/SAPKalpha), which enters
      the nucleus and induces expression of >50 genes, implying that transcriptional up
      regulation is necessary to cope with hyperosmotic stress. Contrary to this
      expectation, we show here that cells lacking the karyopherin required for Hog1
      nuclear import or in which Hog1 is anchored at the plasma membrane (or both) can
      withstand long-term hyperosmotic challenge by ionic and nonionic solutes without
      exhibiting the normal change in transcriptional program (comparable with
      hog1Delta cells), as judged by mRNA hybridization and microarray analysis. For
      such cells to survive hyperosmotic stress, systematic genetic analysis ruled out
      the need for any Hog1-dependent transcription factor, the Hog1-activated MAPKAP
      kinases, or ion, glycerol, and water channels. By contrast, enzymes needed for
      glycerol production were essential for viability. Thus, control of intracellular
      glycerol formation by Hog1 is critical for maintenance of osmotic balance but not
      transcriptional induction of any gene.

PMID- 18719125
TI  - Endogenous oxidative stress produces diversity and adaptability in biofilm
      communities.
AB  - Many bacterial species are capable of biofilm growth, in which cells live and
      replicate within multicellular community groups. Recent work shows that biofilm
      growth by a wide variety of bacterial species can generate genetic diversity in
      microbial populations. This finding is significant because the presence of
      diverse subpopulations can extend the range of conditions in which communities
      can thrive. Here, we used biofilms formed by the pathogen Pseudomonas aeruginosa
      to investigate how this population diversity is produced. We found that some
      cells within biofilms incur double-stranded DNA breaks caused by endogenous
      oxidative stress. Genetic variants then result when breaks are repaired by a
      mutagenic mechanism involving recombinatorial DNA repair genes. We hypothesized
      that the mutations produced could promote the adaptation of biofilm communities
      to changing conditions in addition to generating diversity. To test this idea, we
      exposed biofilms to an antibiotic and found that the oxidative stress-break
      repair mechanism increased the emergence of antibiotic-resistant bacteria. The
      diversity and adaptability produced by this mechanism could help biofilm
      communities survive in harsh environments.

PMID- 18719126
TI  - Dissecting the roles of MuB in Mu transposition: ATP regulation of DNA binding is
      not essential for target delivery.
AB  - Collaboration between MuA transposase and its activator protein, MuB, is
      essential for properly regulated transposition. MuB activates MuA catalytic
      activity, selects target DNA, and stimulates transposition into the selected
      target site. Selection of appropriate target DNA requires ATP hydrolysis by the
      MuB ATPase. By fusing MuB to a site-specific DNA-binding protein, the Arc
      repressor, we generated a MuB variant that could select target DNA independently
      of ATP. This Arc-MuB fusion protein allowed us to test whether ATP binding and
      hydrolysis by MuB are necessary for stimulation of transposition into selected
      DNA, a process termed target delivery. We find that with the fusion proteins, MuB
      dependent target delivery occurs efficiently under conditions where ATP
      hydrolysis is prevented by mutation or use of ADP. In contrast, no delivery was
      detected in the absence of nucleotide. These data indicate that the ATP- and MuA
      regulated DNA-binding activity of MuB is not essential for target delivery but
      that activation of MuA by MuB strictly requires nucleotide-bound MuB.
      Furthermore, we find that the fusion protein directs transposition to regions of
      the DNA within 40-750 bp of its own binding site. Taken together, these results
      suggest that target delivery by MuB occurs as a consequence of the ability of MuB
      to stimulate MuA while simultaneously tethering MuA to a selected target DNA.
      This tethered-activator model provides an attractive explanation for other
      examples of protein-stimulated control of target site selection.

PMID- 18719128
TI  - Structure of apolipoprotein A-I in spherical high density lipoproteins of
      different sizes.
AB  - Spherical high density lipoproteins (HDL) predominate in human plasma. However,
      little information exists on the structure of the most common HDL protein,
      apolipoprotein (apo) A-I, in spheres vs. better studied discoidal forms. We
      produced spherical HDL by incubating reconstituted discoidal HDL with
      physiological plasma-remodeling enzymes and compared apoA-I structure in discs
      and spheres of comparable diameter (79-80 and 93-96 A). Using cross-linking
      chemistry and mass spectrometry, we determined that the general structural
      organization of apoA-I was overall similar between discs and spheres, regardless
      of diameter. This was the case despite the fact that the 93 A spheres contained
      three molecules of apoA-I per particle compared with only two in the discs. Thus,
      apoA-I adopts a consistent general structural framework in HDL particles
      irrespective of shape, size and the number of apoA-Is present. Furthermore, a
      similar cross-linking pattern was demonstrated in HDL particles isolated from
      human serum. We propose the first experiment-based molecular model of apoA-I in
      spherical HDL particles. This model provides a new foundation for understanding
      how apoA-I structure modulates HDL function and metabolism.

PMID- 18719127
TI  - Interleukin-6 regulates pancreatic alpha-cell mass expansion.
AB  - Interleukin-6 (IL-6) is systemically elevated in obesity and is a predictive
      factor to develop type 2 diabetes. Pancreatic islet pathology in type 2 diabetes
      is characterized by reduced beta-cell function and mass, an increased proportion
      of alpha-cells relative to beta-cells, and alpha-cell dysfunction. Here we show
      that the alpha cell is a primary target of IL-6 actions. Beginning with
      investigating the tissue-specific expression pattern of the IL-6 receptor (IL-6R)
      in both mice and rats, we find the highest expression of the IL-6R in the
      endocrine pancreas, with highest expression on the alpha-cell. The islet IL-6R is
      functional, and IL-6 acutely regulates both pro-glucagon mRNA and glucagon
      secretion in mouse and human islets, with no acute effect on insulin secretion.
      Furthermore, IL-6 stimulates alpha-cell proliferation, prevents apoptosis due to
      metabolic stress, and regulates alpha-cell mass in vivo. Using IL-6 KO mice fed a
      high-fat diet, we find that IL-6 is necessary for high-fat diet-induced increased
      alpha-cell mass, an effect that occurs early in response to diet change. Further,
      after high-fat diet feeding, IL-6 KO mice without expansion of alpha-cell mass
      display decreased fasting glucagon levels. However, despite these alpha-cell
      effects, high-fat feeding of IL-6 KO mice results in increased fed glycemia due
      to impaired insulin secretion, with unchanged insulin sensitivity and similar
      body weights. Thus, we conclude that IL-6 is necessary for the expansion of
      pancreatic alpha-cell mass in response to high-fat diet feeding, and we suggest
      that this expansion may be needed for functional beta-cell compensation to
      increased metabolic demand.

PMID- 18719129
TI  - Neutralization of HIV-1 by redirection of natural antibodies.
AB  - The great variability and high glycosylation of gp120 poses a great challenge for
      the design of a functional immune therapy. The binding region of the CD4 receptor
      to gp120, however, is well conserved and may constitute a target to limit viral
      entry and infectivity. Our strategy consists in using a preexisting pool of
      natural antibodies directed toward the gal(alpha1,3)gal disaccharide and to
      redirect it to HIV. We here show that using CD4-derived, gp120-binding, synthetic
      peptides chemically linked to gal(alpha1,3)gal can redirect these natural
      antibodies and improve the HIV-1 neutralizing activity of the CD4-derived
      peptides in vitro. Importantly, the binding of the CD4-gal(alpha1,3)gal peptides
      to HIV-1-infected cells conferred antibody-dependent cellular cytotoxicity after
      the addition of human sera. Thus, the temporary redirection of naturally
      occurring antibodies and their biological activities to a new antigen represents
      a completely new way of targeting a human disease.

PMID- 18719130
TI  - An abnormal rectal flat lesion.

PMID- 18719131
TI  - Purinergic receptors as future targets for treatment of functional GI disorders.

PMID- 18719132
TI  - Surveillance programmes for colorectal cancer in inflammatory bowel disease: have
      we got it right?

PMID- 18719133
TI  - Simple measures to prevent post-ERCP pancreatitis?

PMID- 18719134
TI  - Role of hedgehog signalling in bile ductular cells.

PMID- 18719135
TI  - Ulcers and the colon: keep an open mind.

PMID- 18719136
TI  - Epigastric discomfort after outpatient endoscopy.

PMID- 18719137
TI  - A puzzling presentation of pancreatitis.

PMID- 18719138
TI  - Abdominal pain and shock in a 73-year-old patient.

PMID- 18719139
TI  - Use of sirolimus (rapamycin) to treat refractory Crohn's disease.
AB  - We present the case of a 37-year-old woman with severe refractory colonic and
      perianal Crohn's disease who had lost response to second-line, steroid-sparing
      treatments azathioprine, methotrexate and infliximab. For many such patients
      extensive surgery has often been considered the only option. New insights
      provided by the results of genome-wide association scanning in Crohn's disease
      highlight autophagy, a cellular process implicated in the clearance of
      intracellular bacteria, as a key process in Crohn's disease pathogeneses.
      Sirolimus (rapamycin) is a drug used to upregulate autophagy in cell culture in
      the laboratory, and in clinical practice to prevent rejection following organ
      transplantation due to independent immunosuppressive action. Our patient was
      treated with sirolimus for 6 months at a dose that maintained serum trough levels
      of 5 ng/ml. There was marked and sustained improvement in Crohn's disease
      symptoms with the Harvey-Bradshaw index falling from 13 to 3, in serum markers of
      inflammation (C-reactive protein fell from 79 to 2) and endoscopic appearance.
      This is the first reported case of the use of sirolimus to treat Crohn's disease.

PMID- 18719140
TI  - Metachronous multi-organ lesions in a jaundiced patient.

PMID- 18719141
TI  - Iron deficiency anaemia guidelines: time for an update?

PMID- 18719142
TI  - Crohn's-like enterocolitis associated with mycophenolic acid treatment.

PMID- 18719143
TI  - In vivo diagnosis of intestinal spirochaetosis by confocal endomicroscopy.

PMID- 18719144
TI  - Narrow-band imaging and detection of colorectal adenoma.

PMID- 18719146
TI  - The effects of population-based faecal occult blood test screening upon emergency
      colorectal cancer admissions in Coventry and north Warwickshire.

PMID- 18719147
TI  - The prevalence of small intestinal bacterial overgrowth in irritable bowel
      syndrome: IBS vs healthy controls (not historical definitions).

PMID- 18719148
TI  - More polyp detection: narrow-band imaging or a transparent hood?

PMID- 18719149
TI  - Genetic variants in the autophagy pathway contribute to paediatric Crohn's
      disease.

PMID- 18719150
TI  - Early management of severe acute biliary pancreatitis: wind of change.

PMID- 18719151
TI  - Somatostatin analogues reduce liver volume in polycystic liver disease.

PMID- 18719155
TI  - Fetal alcohol spectrum disorder: counting the invisible - mission impossible?

PMID- 18719156
TI  - Obesity and consequent health risks: is prevention realistic and achievable?

PMID- 18719157
TI  - A 15-year-old boy with digital enlargement.

PMID- 18719158
TI  - Recurrent papular urticaria in a 6-year-old girl.

PMID- 18719161
TI  - Developing and introducing evidence based clinical practice guidelines for
      serious illness in Kenya.

PMID- 18719162
TI  - Plagiocephaly, brachycephaly and cranial orthotic devices: misshapen heads and
      helmets.

PMID- 18719164
TI  - What is the role of helmet therapy in positional plagiocephaly?

PMID- 18719165
TI  - Head moulding for plagiocephaly.

PMID- 18719166
TI  - Is targeted hepatitis B vaccination working?

PMID- 18719168
TI  - Paediatric A&E attendances; findings and consequences.

PMID- 18719167
TI  - Reducing the incidence of neonatal hypernatraemic dehydration.

PMID- 18719169
TI  - Varicella vaccination for HIV-infected children.

PMID- 18719172
TI  - Acanthamoeba and the blood-brain barrier: the breakthrough.
AB  - Acanthamoeba granulomatous encephalitis is a rare disease that almost always
      proves fatal. Death occurs mainly due to neurological complications; however, the
      pathogenesis and pathophysiology associated with this disease remain incompletely
      understood. Haematogenous spread is a key step in the development of Acanthamoeba
      encephalitis, but it is not clear how circulating amoebae breakthrough the blood
      brain barrier to gain entry into the central nervous system to produce the
      disease. This review of the literature describes the parasite factors and immune
      mediated mechanisms involved in the blood-brain barrier dysfunction leading to
      neuropathogenesis.

PMID- 18719173
TI  - Differential glycosaminoglycan binding of Chlamydia trachomatis OmcB protein from
      serovars E and LGV.
AB  - We recently showed that OmcB protein from Chlamydia trachomatis serovar LGV1
      functions as an adhesin. In this study, we produced Escherichia coli expressing
      OmcB from serovar E and compared this OmcB to OmcB from serovar LGV1. Infectivity
      inhibition assays carried out with serovars LGV1 and E of C. trachomatis in the
      presence of recombinant OmcB showed considerable (approximately 60%) inhibition
      of infectivity. In the presence of heparan sulphate, there was significant
      inhibition (68%) of adherence of E. coli expressing OmcB from serovar LGV1 only.
      In a further experiment, recombinant OmcB from serovar LGV1 showed minimal
      binding to glycosaminoglycan (GAG)-deficient cells, whilst to the same cells,
      recombinant OmcB from serovar E showed binding equal to that to the wild-type
      cells. Our experiments strongly suggest that OmcB from serovar E, in contrast to
      that from serovar LGV1, is not binding to host cells through a GAG-dependent
      mechanism.

PMID- 18719174
TI  - Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns
      between western and East Asian strains, and influences on interleukin-8
      secretion.
AB  - Helicobacter pylori strains from East Asia have an 'East Asian' type of CagA that
      is more active and predominantly comprises a single type. Strains from other
      countries have a 'western' type of CagA, which is less active and comprises many
      different types generated by intragenomic recombination. Co-culture of AGS
      gastric epithelial cells with isolates of western strains that displayed
      microevolution in CagA showed that isolates with additional copies of the C motif
      induced significantly more interleukin (IL)-8 secretion. Co-culture of AGS cells
      with western and East Asian strains, each expressing CagA with a single copy of
      the C or D motif, showed that East Asian strains induced significantly more IL-8
      secretion. Analysis of the different CagA types from data deposited in GenBank
      and from the literature showed that western CagA is significantly more likely to
      undergo duplication of tyrosine phosphorylation motif C than East Asian CagA is
      of the corresponding D motif. Taken together, the data suggest that the already
      highly active East Asian CagA with one D motif has no requirement to increase its
      virulence, whereas the less active western CagA displays flexibility in its
      capacity to increase its number of tyrosine phosphorylation motifs to become more
      virulent.

PMID- 18719175
TI  - Identification of virulence determinants in uropathogenic Proteus mirabilis using
      signature-tagged mutagenesis.
AB  - The Gram-negative bacterium Proteus mirabilis causes urinary tract infections
      (UTIs) in individuals with long-term indwelling catheters or those with
      functional or structural abnormalities of the urinary tract. Known virulence
      factors include urease, haemolysin, fimbriae, flagella, DsbA, a phosphate
      transporter and genes involved in cell-wall synthesis and metabolism, many of
      which have been identified using the technique of signature-tagged mutagenesis
      (STM). To identify additional virulence determinants and to increase the
      theoretical coverage of the genome, this study generated and assessed 1880 P.
      mirabilis strain HI4320 mutants using this method. Mutants with disruptions in
      genes vital for colonization of the CBA mouse model of ascending UTI were
      identified after performing primary and secondary in vivo screens in
      approximately 315 CBA mice, primary and secondary in vitro screens in both Luria
      broth and minimal A medium to eliminate mutants with minor growth deficiencies,
      and co-challenge competition experiments in approximately 500 CBA mice. After
      completion of in vivo screening, a total of 217 transposon mutants were
      attenuated in the CBA mouse model of ascending UTI. Following in vitro screening,
      this number was reduced to 196 transposon mutants with a probable role in
      virulence. Co-challenge competition experiments confirmed significant attenuation
      for 37 of the 93 transposon mutants tested, being outcompeted by wild-type
      HI4320. Following sequence analysis of the 37 mutants, transposon insertions were
      identified in genes including the peptidyl-prolyl isomerases surA and ppiA,
      glycosyltransferase cpsF, biopolymer transport protein exbD, transcriptional
      regulator nhaR, one putative fimbrial protein, flagellar M-ring protein fliF and
      hook protein flgE, and multiple metabolic genes.

PMID- 18719176
TI  - Characterization of T-cell immunogenicity of two PE/PPE proteins of Mycobacterium
      tuberculosis.
AB  - The PE and PPE proteins of Mycobacterium tuberculosis form a source of antigenic
      variation among different strains of this bacterium. Two of the PE_PGRS protein
      encoding genes, rv3812 and rv3018c, are expressed in pathogenic mycobacteria and
      are implicated, respectively, in the persistence of the organism in macrophages
      and in virulence. Peptides derived from these proteins have been predicted to
      bind major histocompatibility complex (MHC) class I with high affinity on the
      basis of immunoinformatics analysis, suggesting a possible role for these
      proteins in antimycobacterial immunity. In the present work, using DNA constructs
      containing the rv3812 and rv3018c genes of M. tuberculosis, the immunogenicity of
      these proteins was demonstrated in BALB/c mice. Immunization with either DNA
      construct induced a significant number of CD8+-type T cells and a strong Th1-type
      response, with high gamma interferon (IFN-gamma) and low interleukin-4 responses.
      Three nonameric peptides of Rv3812 and two of Rv3018c elicited a strong T-cell
      response in an MHC-restricted manner. An epitope-specific response was
      demonstrated by the lysis of peptide-pulsed antigen-presenting cells, release of
      perforin and IFN-gamma production. Experimentally, these peptides bound with high
      affinity to MHC H-2Kd and showed low dissociation rates of peptide-MHC complexes.
      This study suggests that the identified T-cell epitopes may contribute to
      immunity against tuberculosis if included in a vaccine.

PMID- 18719178
TI  - Novel hypertonic saline-sodium hydroxide (HS-SH) method for decontamination and
      concentration of sputum samples for Mycobacterium tuberculosis microscopy and
      culture.
AB  - This study evaluated a new decontamination and concentration (DC) method for
      sputum microscopy and culture. Sputum samples from patients with suspected
      pulmonary tuberculosis (TB) (n=106) were tested using the proposed hypertonic
      saline-sodium hydroxide (HS-SH) DC method, the recommended N-acetyl-L-cysteine
      sodium citrate-sodium hydroxide (NALC-NaOH) DC method and unconcentrated direct
      smear (Ziehl-Neelsen) techniques for the presence of mycobacteria using
      Lowenstein-Jensen culture and light microscopy. Of 94 valid specimens, 21 (22.3%)
      were positive in culture and were further characterized as Mycobacterium
      tuberculosis. The sensitivity for acid-fast bacilli (AFB) smears was increased
      from 28.6% using the direct method to 71.4% (HS-SH) and 66.7% (NALC-NaOH) using
      DC methods. Both concentration techniques were highly comparable for culture
      (kappa=0.794) and smear (kappa=0.631) for AFB. Thus the proposed HS-SH DC method
      improved the sensitivity of AFB microscopy compared with a routine unconcentrated
      direct smear; its performance was comparable to that of the NALC-NaOH DC method
      for AFB smears and culture, but it was methodologically simpler and less
      expensive, making it a promising candidate for evaluation by national TB control
      programmes in developing countries.

PMID- 18719179
TI  - Detection and differentiation of Cryptosporidium hominis and Cryptosporidium
      parvum by dual TaqMan assays.
AB  - Rapid identification of the two major species of Cryptosporidium associated with
      human infections, Cryptosporidium hominis and Cryptosporidium parvum, is
      important for investigating outbreaks of cryptosporidiosis. This study reports
      the development and validation of a real-time PCR TaqMan procedure for detection
      of Cryptosporidium species and identification of C. hominis and C. parvum in
      stool specimens. This procedure comprised a generic TaqMan assay targeting the
      18S rRNA for sensitive detection of Cryptosporidium species, as well as two other
      TaqMan assays for identification of C. hominis and C. parvum. The generic
      Cryptosporidium species assay can be duplexed with the C. parvum-specific assay.
      The generic Cryptosporidium species assay was able to detect ten Cryptosporidium
      species and did not cross-react with a panel of ten other protozoan parasites.
      The generic Cryptosporidium species assay could detect 1-10 oocysts in a 300
      microl stool specimen, whilst each of the species-specific TaqMan assays had
      detection sensitivities that were approximately tenfold higher. The 18S rRNA
      assay was found to detect Cryptosporidium species in 49/55 DNA extracts from
      stool specimens containing either C. hominis or C. parvum. The C. hominis TaqMan
      assay correctly identified C. hominis in 24/31 validation panel specimens
      containing this species. The C. parvum-specific assay correctly identified C.
      parvum in 21/24 validation panel specimens containing this species. This real
      time PCR procedure was used to detect and identify C. hominis and C. parvum in
      stool specimens from outbreak investigations in the USA and Botswana, resulting
      in identification of C. hominis and/or C. parvum in 66/67 stool specimens shown
      to be positive for these species using other techniques. From the outbreak
      specimens tested, the TaqMan procedure was found to have a specificity of 94%.
      This TaqMan PCR procedure should be a valuable tool for the laboratory diagnosis
      of cryptosporidiosis caused by C. hominis and C. parvum during outbreak
      investigations.

PMID- 18719180
TI  - Comparative prevalence of superantigenic toxin genes in meticillin-resistant and
      meticillin-susceptible Staphylococcus aureus isolates.
AB  - A total of 118 meticillin-resistant Staphylococcus aureus (MRSA) and 140
      meticillin-susceptible S. aureus (MSSA) isolates from different patients in the
      same time period were comprehensively searched using a multiplex PCR for the
      classical and recently described superantigenic toxin gene family comprising the
      staphylococcal enterotoxin genes sea to ser and the toxic shock syndrome toxin 1
      gene, tst-1. Both MRSA and MSSA isolates carried a number of superantigenic toxin
      genes, but the MRSA isolates harboured more superantigenic toxin genes than the
      MSSA isolates. The most frequent genotype of the MRSA isolates was sec, sell and
      tst-1 together with the gene combination seg, sei, selm, seln and selo, which was
      found strictly in combination in 69.5% of the isolates tested. In contrast,
      possession of the sec, sell and tst-1 genes in MSSA isolates was significantly
      less than in MRSA (2.1 vs 77.1%, respectively), although they also often
      contained the combination genes (25.0%). This notable higher prevalence in MRSA
      isolates indicated that possession of the sec, sell and tst-1 genes in particular
      appeared to be a habitual feature of MRSA. Moreover, these were mainly due to the
      fixed combinations of the mobile genetic elements type I nuSa4 encoding sec, sell
      and tst-1, and type I nuSabeta encoding seg, sei, selm, seln and selo. Analysis
      of the relationship between toxin genotypes and the toxin gene-encoding profiles
      of mobile genetic elements has a possible role in determining superantigenic
      toxin genotypes in S. aureus.

PMID- 18719177
TI  - Serum antibodies to West Nile virus in naturally exposed and vaccinated horses.
AB  - A polyvalent ELISA and plaque reduction neutralization tests (PRNTs) were used to
      measure serum antibodies to West Nile virus (WNV) in horses naturally exposed to
      or vaccinated against this flavivirus in Connecticut and New York State, USA.
      Relying on a PRNT as a 'gold standard', the main objective was to validate a
      modified ELISA containing a recombinant WNV envelope protein antigen. It was also
      important to assess specificity by testing sera from horses that had other,
      undiagnosed illnesses. Sera for the latter study were obtained from 43 privately
      owned horses during 1995-1996. Analyses by an ELISA and a PRNT confirmed the
      presence of WNV antibodies in 21 (91%) of 23 sera from naturally exposed horses
      and in 85% of the 20 vaccinated subjects; overall results for both study groups
      were highly concordant (91% agreement). Humoral responses of naturally exposed
      and immunized horses were similar. Both serological tests were useful in
      confirming past infections with WNV, but there was no evidence that horses with
      undiagnosed illnesses were exposed to WNV prior to a 1999 outbreak in
      Connecticut, USA.

PMID- 18719181
TI  - Human recombinant lactoferrin acts synergistically with antimicrobials commonly
      used in neonatal practice against coagulase-negative staphylococci and Candida
      albicans causing neonatal sepsis.
AB  - Neonatal sepsis causes significant mortality and morbidity. Coagulase-negative
      staphylococci (CoNS) and Candida frequently cause neonatal sepsis at >72 h of
      age. Lactoferrin, which is present in human milk, is a component of innate
      immunity and has broad-spectrum antimicrobial activity. The synergistic effects
      of lactoferrin with antibiotics against neonatal isolates have not been
      systematically evaluated. Here, eight clinical strains (seven neonatal) of CoNS
      and three strains (two neonatal) of Candida albicans were studied. MIC50 and
      MIC90 values of human recombinant lactoferrin (talactoferrin; TLF), vancomycin
      (VAN) and nafcillin (NAF) against CoNS, and of TLF, amphotericin B (AMB) and
      fluconazole (FLC) against C. albicans, were evaluated according to established
      guidelines. Antimicrobial combinations of TLF with NAF or VAN against CoNS, and
      TLF with AMB or FLC against C. albicans, were evaluated by a checkerboard method
      with serial twofold dilutions. Synergy was evaluated by the median effects
      principle, and combination indices and dose reduction indices were reported at
      50, 75 and 90% inhibitory effect at several drug-dose ratios. It was found that
      TLF acted synergistically with NAF and VAN against CoNS, and with AMB and FLC
      against C. albicans, at multiple dose effects and drug-dose ratios with few
      exceptions. In synergistic combinations, drug reduction indices indicated a
      significant reduction in doses of antibiotics, which may be clinically relevant.
      Thus TLF acts synergistically with anti-staphylococcal and anti-Candida agents
      commonly used in neonatal practice and is a promising agent that needs to be
      evaluated in clinical studies.

PMID- 18719182
TI  - Penicillin resistance in the intestinal spirochaete Brachyspira pilosicoli
      associated with OXA-136 and OXA-137, two new variants of the class D beta
      lactamase OXA-63.
AB  - Penicillin resistance mediated by beta-lactamase activity has been reported
      previously in the anaerobic intestinal spirochaete Brachyspira pilosicoli, and a
      novel class D beta-lactamase (OXA-63) hydrolysing oxacillin was described
      recently in a resistant human strain from France. In the current study, 18 B.
      pilosicoli strains from Australia and Papua New Guinea were tested for ampicillin
      and oxacillin susceptibility, and investigated for the presence of the class D
      beta-lactamase gene blaOXA-63 using PCR. PCR products were amplified from seven
      human and four porcine strains that were penicillin resistant, but not from seven
      penicillin-sensitive strains. Sequence analysis of the whole gene amplified from
      seven of the resistant strains from humans and pigs revealed only minor
      nucleotide differences among them, but there were significant differences
      compared with blaOXA-63. The predicted amino acid sequence of the enzyme from all
      seven strains had the same key structural motifs as the previously reported OXA
      63, but two variants with 94-95% identity with OXA-63 were identified. OXA-136
      had an additional amino acid and 12 other consistent amino acid substitutions
      compared with OXA-63. OXA-137 had the same differences compared with OXA-63 as
      OXA-136, but had an additional amino acid substitution at position 16. No
      structures consistent with integrons or transposons were found in the nucleotide
      sequences in the vicinity of blaOXA-136 in partially sequenced B. pilosicoli
      strain 95/1000, and the GC content (25.2 mol%) of the gene was similar to that of
      the whole genome. The gene encoding OXA-136 from B. pilosicoli strain Cof-10
      conferred penicillin resistance on Escherichia coli. This study shows that
      penicillin resistance in human and porcine B. pilosicoli strains from Australia
      is associated with the production of two variants of OXA-63, and that susceptible
      strains lack the genes encoding OXA-63 or the variants.

PMID- 18719183
TI  - Enhancement of the antituberculosis activity of weak acids by inhibitors of
      energy metabolism but not by anaerobiosis suggests that weak acids act
      differently from the front-line tuberculosis drug pyrazinamide.
AB  - Mycobacterium tuberculosis is uniquely susceptible to weak acids compared with
      other mycobacteria or bacteria. The antituberculosis activity of the front-line
      drug pyrazinamide (PZA), a weak acid (pyrazinoic acid) precursor, can be enhanced
      by inhibitors of energy metabolism and anaerobiosis. Here, we investigated the
      effect of inhibitors of energy metabolism and anaerobiosis on weak acid activity
      against M. tuberculosis in general. The susceptibility of M. tuberculosis to
      benzoic acid (BA) esters and amides was determined alone and in the presence of
      inhibitors of energy metabolism such as N,N'-dicyclohexylcarbodiimide (DCCD) and
      azide and also under anaerobic conditions in the form of MIC and drug exposure
      followed by colony count. Some BA esters such as propyl hydroxybenzoic acid and 4
      dodecyloxylbenzoic acid had significant activity whereas amides of BA had no
      activity. As for PZA, inhibitors of energy metabolism DCCD and azide enhanced the
      antituberculosis activity of weak acids under normal atmospheric oxygen tension.
      However, unlike PZA, weak acids did not show antituberculosis activity and the
      inhibitors of energy metabolism did not enhance the weak acid activity under
      anaerobic conditions. The enhancement of weak acid activity by inhibitors of
      energy metabolism for M. tuberculosis was not seen in other bacterial species
      such as Helicobacter pylori. These results suggest that while the
      antituberculosis activity of weak acids can be enhanced by inhibitors of energy
      metabolism as for PZA, weak acids act differently from PZA in that they were
      inactive against M. tuberculosis under anaerobic conditions. The significance of
      these findings is discussed in the context of the unique physiology of M.
      tuberculosis and the development of new tuberculosis drugs.

PMID- 18719184
TI  - Effect of triclosan on the formation of crystalline biofilms by mixed communities
      of urinary tract pathogens on urinary catheters.
AB  - The crystalline bacterial biofilms that encrust Foley catheters compromise the
      care of many elderly and disabled patients. The aim of this study was to examine
      whether the biocide triclosan can prevent encrustation by the mixed flora of
      uropathogens that commonly infect patients undergoing long-term catheterization.
      Models of the catheterized bladder were inoculated with communities of organisms
      isolated from patients who were experiencing catheter blockage. The catheter
      retention balloons were inflated with water or triclosan (3 g triclosan l(-1) in
      0.1 M sodium carbonate) and urine was supplied to the models for up to 7 days.
      The effect of triclosan was recorded on the viable cell populations, the pH of
      the residual urine and the times that catheters took to block. The extent of
      encrustation of the catheters was visualized by scanning electron microscopy. In
      models inoculated with communities containing Proteus mirabilis, triclosan
      prevented the rise in urinary pH that drives crystalline biofilm formation and
      catheter blockage. The biocide had no effect on populations of Enterococcus
      faecalis and Pseudomonas aeruginosa, but Proteus mirabilis, Escherichia coli and
      Klebsiella pneumoniae were eliminated from the residual urine and the catheters
      drained freely for the 7-day experimental period. In models inoculated with a
      mixed community containing Providencia rettgeri, catheters inflated with
      triclosan continued to block rapidly. Although K. pneumoniae and Proteus vulgaris
      were eliminated from the residual urine, there was no effect on the viability of
      Providencia rettgeri. The results indicate that the triclosan strategy should be
      limited to the treatment of patients who are infected with Proteus mirabilis.

PMID- 18719185
TI  - Enteroaggregative Escherichia coli associated with a foodborne outbreak of
      gastroenteritis.
AB  - This study investigated two foodborne outbreaks of gastroenteritis that occurred
      10 days apart among individuals who had meals at the restaurant of a farm holiday
      resort. Mild gastrointestinal symptoms were reported and none of the patients
      needed hospitalization. Mean incubation times were 45 and 33 h, and the overall
      attack rates were 43.5 and 58.3%, respectively. Stool sample examination was
      negative for common enteric pathogens in both outbreaks. Specimens from 13 people
      involved in the second outbreak and 3 restaurant staff were examined for
      diarrhoeagenic Escherichia coli. An enteroaggregative E. coli (EAEC) strain of
      serotype O92:H33 was isolated from six participants and one member of staff. In
      particular, the EAEC strain was isolated from five of the six cases of diarrhoea
      examined. The strain showed an aggregative pattern of adherence to HEp-2 cells,
      did not produce a biofilm and possessed the virulence-related genes aat, aggR,
      aap and set1A, but not the astA gene. A retrospective cohort study indicated a
      pecorino cheese made with unpasteurized sheep milk as the possible source
      (P<0.001). Samples of the cheese had E. coli counts higher than 10(6) c.f.u. g(
      1), but the outbreak EAEC strain was not isolated. This report confirms that EAEC
      infections are probably underdiagnosed because of the limited availability of
      laboratories capable of identifying this group of pathogenic E. coli.

PMID- 18719186
TI  - Influence of automated screening and confirmation of extended-spectrum beta
      lactamase-producing members of the Enterobacteriaceae on prescribing of
      antibiotics.
AB  - This study investigated the clinician response to the extended-spectrum beta
      lactamase (ESBL) confirmation report generated by an automated detection system,
      MicroScan Walkaway. The study compared two cohorts (pre- and post-automated
      detection) of patients with an ESBL-producing Escherichia coli or Klebsiella
      species non-urinary infection over the period October 2001-December 2006.
      Acceptance of the report, as defined by the initiation of carbapenem therapy, was
      observed in 69.2% of the post-automated detection cohort (n=78) versus 20% in the
      pre-automated detection period (n=15) (P<or=0.001). The utilization of a
      carbapenem increased progressively over the course of the study. Moreover, the
      time to initiation of carbapenem therapy was reduced from 15.7+/-4.9 to 0.1+/-2.0
      days (P<or=0.001) after implementation of this automated detection system.
      Overall, clinicians responded positively to the ESBL automated detection report,
      as gauged by the increased utilization of a carbapenem and the earlier initiation
      of appropriate therapy; however, reductions in length of stay and mortality were
      not observed in this infected population.

PMID- 18719187
TI  - Secreted subtilisins of Microsporum canis are involved in adherence of
      arthroconidia to feline corneocytes.
AB  - Microsporum canis is a pathogenic fungus that causes a superficial cutaneous
      infection called dermatophytosis, mainly in cats and humans. The mechanisms
      involved in adherence of M. canis to epidermis have never been investigated.
      Here, a model was developed to study the adherence of M. canis to feline
      corneocytes through the use of a reconstructed interfollicular feline epidermis
      (RFE). In this model, adherence of arthroconidia to RFE was found to be time
      dependent, starting at 2 h post-inoculation and still increasing at 6 h.
      Chymostatin, a serine protease inhibitor, inhibited M. canis adherence to RFE by
      53%. Moreover, two mAbs against the keratinolytic protease subtilisin 3 (Sub3)
      inhibited M. canis adherence to RFE by 23%, suggesting that subtilisins, and Sub3
      in particular, are involved in the adherence process.

PMID- 18719188
TI  - Spondylodiscitis and paraspinal abscess caused by beta-haemolytic group G
      streptococci spreading from infected leg ulcers.
AB  - We report a case of spondylodiscitis due to Streptococcus dysgalactiae subsp.
      equisimilis spreading from infected leg ulcers. The route of infection could be
      unequivocally demonstrated by culturing identical isolates from leg wounds, blood
      culture and intra-surgery specimens from the spine. The present case illustrates
      the pathogenic potential of group G streptococci also for non-diabetic adults.

PMID- 18719189
TI  - Brucellosis complicating chronic non-infectious disorders: diagnostic and
      therapeutic dilemmas.
AB  - There is little information in the literature on the clinical progress of
      brucellosis in patients affected by other non-infectious diseases; however, the
      infection can often trigger an exacerbation of existing underlying conditions in
      certain target organs. In this report we present four cases of brucellosis
      complicating previous diseases, and the difficulties in relation to their
      diagnosis and treatment. The study involved four patients with the following
      disorders: polycythaemia vera, pulmonary fibrosis, cirrhosis of the liver and
      arthritis of the knee. Brucellosis was diagnosed by classical serological and
      bacteriological methods. The strains involved could be isolated only in three of
      the four patients: two strains were Brucella abortus biovar 1 and one was
      Brucella suis biovar 1. Two patients relapsed 10 and 7 months after admission,
      another presented chronic brucellosis and received various therapy schemes, and
      one died. Since the best selection of antibiotics and the optimal duration of
      therapy remain unknown for patients having brucellosis complicated by previous
      pathologies, these remain at the discretion of the attending physician.
      Management of our patients was controversial in terms of the selection of
      antibiotics, duration of treatment and decision regarding surgery.

PMID- 18719190
TI  - Graft versus host disease-related Hafnia alvei colonization and probable
      infection.
AB  - We describe the case of a graft versus host disease (GvHD) patient, in whom
      Hafnia alvei was cultured as a single organism, and at high bacterial counts from
      stool samples, from the onset of the disease until its resolution. This case is a
      further example of the contentious role of this species in causing human
      intestinal disease. Furthermore, it focuses on enteric damage by GvHD as a risk
      factor for acquiring H. alvei colonization, and probably infection.

PMID- 18719191
TI  - First case of post-endoscopic retrograde cholangiopancreatography bacteraemia
      caused by Acinetobacter ursingii in a patient with choledocholithiasis and
      cholangitis.
AB  - We describe what we believe to be the first case of biliary sepsis caused by
      Acinetobacter ursingii. The patient was a healthy woman with no comorbidities who
      presented with choledocholithiasis and cholangitis. The performance of an
      endoscopic cholangiopancreatography was the trigger for A. ursingii bacteraemia.
      This report highlights the inadequacies of conventional phenotypic tests usually
      available in clinical microbiology laboratories for the identification of
      Acinetobacter species.

PMID- 18719192
TI  - Activation of p38 mitogen-activated protein kinase module facilitates in vitro
      host cell invasion by Rickettsia rickettsii.

PMID- 18719193
TI  - vir types of Streptococcus pyogenes in Chennai, South India.

PMID- 18719194
TI  - Three cases of community-associated meticillin-resistant Staphylococcus aureus
      infection in China.

PMID- 18719195
TI  - First community-acquired meticillin-resistant Staphylococcus aureus in Malaysia.

PMID- 18719196
TI  - Analysis of microRNAs in pancreatic fine-needle aspirates can classify benign and
      malignant tissues.
AB  - BACKGROUND: MicroRNAs (miRNAs) are RNA molecules that are involved in the
      regulation of many cellular processes, including those related to human cancers.
      The aim of this study was to determine, as a proof of principle, whether specific
      candidate miRNAs could be detected in fine-needle aspirate (FNA) biopsies of
      pancreatic ductal adenocarcinoma (PDAC) and could accurately differentiate
      malignant from benign pancreatic tissues. METHODS: We used TaqMan(R) assays to
      quantify miRNA levels in FNA samples collected in RNARetain (n = 16) and compared
      the results with a training set consisting of frozen macrodissected pancreatic
      samples (n = 20). RESULTS: Quantitative reverse-transcription PCR analysis
      confirmed that miRNA levels are affected in PDAC FNAs and correlate well with the
      changes observed in the training set of frozen pancreatic samples. Analysis of
      the amounts produced for a few specific miRNAs enabled identification of PDAC
      samples. The combination of miR-196a and miR-217 biomarkers further improved the
      ability to distinguish between healthy tissue, PDAC, and chronic pancreatitis in
      the training set (P = 8.2 x 10(-10)), as well as segregate PDAC FNA samples from
      other FNA samples (P = 1.1 x 10(-5)). Furthermore, we showed that miR-196a
      production is likely specific to PDAC cells and that its incidence paralleled the
      progression of PDAC. CONCLUSIONS: To the best of our knowledge, this study is the
      first to evaluate the diagnostic potential of miRNAs in a clinical setting and
      has shown that miRNA analysis of pancreatic FNA biopsy samples can aid in the
      pathologic evaluation of suspicious cases and may provide a new strategy for
      improving the diagnosis of pancreatic diseases.

PMID- 18719197
TI  - Intraplatform reproducibility and technical precision of gene expression
      profiling in 4 laboratories investigating 160 leukemia samples: the DACH study.
AB  - BACKGROUND: Gene expression profiling has the potential to offer consistent,
      objective diagnostic test results once a standardized protocol has been
      established. We investigated the robustness, precision, and reproducibility of
      microarray technology. METHODS: One hundred sixty individual patient samples
      representing 11 subtypes of acute and chronic leukemias, myelodysplastic
      syndromes, and nonleukemia as a control group were centrally collected and
      diagnosed as part of the daily routine in the Munich Leukemia Laboratory. The
      custom AmpliChip Leukemia research microarray was used for technical analyses of
      quadruplicate mononuclear cell lysates in 4 different laboratories in Germany
      (D), Austria (A), and Switzerland (CH) (the DACH study). RESULTS: Total-RNA
      preparations were successfully performed in 637 (99.5%) of 640 cases. Mean
      differences between pairs of laboratories in the total-RNA yield from the same
      sample ranged from 0.02 mug to 1.03 mug. Further processing produced 622
      successful in vitro transcription reactions (97.6%); the mean differences between
      laboratories in the cRNA yield from the same sample ranged from 0.40 mug to 6.18
      mug. After hybridization to microarrays, a mean of 47.6%, 46.5%, 46.2%, and 46.4%
      of probe sets were detected as present for the 4 laboratories, with mean signal
      intensity scaling factors of 3.1, 3.7, 4.0, and 4.2, respectively. In
      unsupervised hierarchical cluster and principal component analyses, replicates
      from the same patient always clustered closely together, with no indications of
      any association between gene expression profiles due to different operators or
      laboratories. CONCLUSIONS: Microarray analysis can be performed with high
      interlaboratory reproducibility and with comparable quality and high technical
      precision across laboratories.

PMID- 18719198
TI  - Quality specifications for the determination of copper, zinc, and selenium in
      human serum or plasma: evaluation of an approach based on biological and
      analytical variation.
AB  - BACKGROUND: Trace element external quality assessment schemes monitor laboratory
      performance and provide a stimulus for improvement in accuracy. However,
      monitoring of participant performance varies according to the scheme and can lead
      to conflicting conclusions. METHODS: Quality specifications based on biological
      intra- and interindividual variability were calculated and compared to those
      currently used by various trace element external quality assessment schemes for
      plasma or serum copper, zinc, and selenium concentrations. For this purpose, we
      evaluated results reported by participating laboratories in different schemes, at
      key concentrations, using z scores. RESULTS: Minimal quality specifications
      developed from the biological intra- and interindividual variability were, for
      Cu, +/-0.84 micromol/L or 12% of the assigned target concentration, whichever is
      greater; for Zn, +/-1.20 micromol/L or 15% of the assigned target concentration,
      whichever is greater; and for Se, +/-0.072 micromol/L or 12% of the assigned
      target concentration, whichever is greater. Reported performance of the
      participating laboratories depended on analyte, concentration, and the selected
      quality specification. In addition, the most commonly used methods for the
      determination of Cu, Zn, and Se may give different results. CONCLUSIONS: The
      proposed minimal quality specifications based on biological variation are
      generally slightly less stringent than those currently in use, although they do
      not drastically change the performance evaluation in the different schemes. These
      specifications are a first step in the harmonization of practices among the
      schemes and remain to be evaluated.

PMID- 18719199
TI  - Serum total prolactin and monomeric prolactin reference intervals determined by
      precipitation with polyethylene glycol: evaluation and validation on common
      immunoassay platforms.
AB  - BACKGROUND: Macroprolactin is an important source of immunoassay interference
      that commonly leads to misdiagnosis and mismanagement of hyperprolactinemic
      patients. We used the predominant immunoassay platforms for prolactin to assay
      serum samples treated with polyethylene glycol (PEG) and establish and validate
      reference intervals for total and monomeric prolactin. METHODS: We used the
      Architect (Abbott), ADVIA Centaur and Immulite (Siemens Diagnostics), Access
      (Beckman Coulter), Elecsys (Roche Diagnostics), and AIA (Tosoh) analyzers with
      samples from healthy males (n = 53) and females (n = 93) to derive parametric
      reference intervals for total and post-PEG monomeric prolactin. Concentrations of
      immunoreactive prolactin isoforms in serum samples from healthy individuals were
      established by gel filtration chromatography (GFC). We then used samples from 22
      individuals whose hyperprolactinemia was entirely attributable to macroprolactin
      and 32 patients with true hyperprolactinemia to compare patient classifications
      and prolactin concentrations measured by GFC with the newly derived post-PEG
      reference intervals. RESULTS: Parametric reference intervals for post-PEG
      prolactin in male and female serum samples, respectively, were (in mIU/L): 61
      196, 66-278 (Centaur); 63-245, 75-381 (Elecsys); 70-301, 92-469 (Access); 72-229,
      79-347 (Architect); 73-247, 83-383 (AIA); and 78-263, 85-394 (Immulite).
      Concordance between GFC and immunoassay-specific post-PEG reference intervals was
      observed in 311 of 324 cases and for 31 of 32 patients with true
      hyperprolactinemia and 17 of 22 patients with macroprolactinemia. Results leading
      to misclassification occurred in a few analyzers for 5 macroprolactinemia patient
      samples with relatively minor increases in post-PEG prolactin (mean 61 mIU/L).
      CONCLUSIONS: Our validated normative reference data for sera pretreated with PEG
      and analyzed on the most commonly used immunoassay platforms should facilitate
      the more widespread introduction of macroprolactin screening by clinical
      laboratories.

PMID- 18719200
TI  - Multiplex enzyme assay screening of dried blood spots for lysosomal storage
      disorders by using tandem mass spectrometry.
AB  - BACKGROUND: Reports of the use of multiplex enzyme assay screening for Pompe
      disease, Fabry disease, Gaucher disease, Niemann-Pick disease types A and B, and
      Krabbe disease have engendered interest in the use of this assay in newborn
      screening. We modified the assay for high-throughput use in screening
      laboratories. METHODS: We optimized enzyme reaction conditions and procedures for
      the assay, including the concentrations of substrate (S) and internal standard
      (IS), assay cocktail compositions, sample clean-up procedures, and mass
      spectrometer operation. The S and IS for each enzyme were premixed and bottled at
      an optimized molar ratio to simplify assay cocktail preparation. Using the new
      S:IS ratio, we validated the modified assay according to CLSI guidelines.
      Stability of the S, IS, and assay cocktails were investigated. Dried blood spots
      from 149 healthy adults, 100 newborns, and 60 patients with a lysosomal storage
      disorder (LSD) were tested using the modified assay. RESULTS: In our study, the
      median enzyme activity measured in adults was generally increased 2-3-fold
      compared to the original method, results indicating higher precision. In the
      multiplex format, each of the 5 modified enzyme assays enabled unambiguous
      differentiation between samples from healthy individuals (adults and newborns)
      and the corresponding disease-specific samples. CONCLUSIONS: The modified
      multiplex enzyme assay with premixed S and IS is appropriate for use in high
      throughput screening laboratories.

PMID- 18719201
TI  - Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non
      small cell lung cancer by quantitative real-time RT-PCR.
AB  - BACKGROUND: microRNA (miRNA) expression profiles are being intensively
      investigated for their involvement in carcinogenesis. We evaluated the prognostic
      value of mature microRNA-21 (miR-21) and mature microRNA-205 (miR-205)
      overexpression in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We
      studied 48 pairs of NSCLC fresh frozen tissue specimens collected at time of
      surgery and before chemotherapy. Highly specific amplification and quantification
      of mature miR-21 and mature miR-205 was achieved using looped real time RT-PCR.
      RESULTS: miRNA expression, determined by real time RT-PCR, was defined by
      DeltaDeltaCt measurements. We detected overexpression of mature miR-21 in 25
      (52.0%) of the 48 NSCLC paired specimens and overexpression of miR-205 in 31
      (64.6%). Overexpression was assessed after comparison of miRNA expression in
      NSCLC tissues and in their corresponding noncancerous tissues with respect to U6
      expression. During the follow-up period, 29 of 48 (60.4%) patients relapsed, and
      23 of 48 died (47.9%). Mature miR-21 was upregulated in 16 of 29 (55.2%) patients
      who relapsed and 15 of 23 (65.2%) patients who died. Mature miR-205 was
      overexpressed in 19 of 29 patients who relapsed (65.5%) and 15 of 23 patients who
      died (65.2%). Mature miR-21 overexpression correlated with overall survival (OS)
      of the patients (P = 0.027), whereas overexpression of mature miR-205 did not.
      CONCLUSIONS: Our results suggest that overexpression of mature miR-21 is an
      independent negative prognostic factor for OS in NSCLC patients.

PMID- 18719203
TI  - Controlled clinical trials and practice-based research in dentistry.

PMID- 18719204
TI  - Biological detoxification and mercury dental amalgam.

PMID- 18719205
TI  - Variation in the human dentition: some past advances and future opportunities.

PMID- 18719206
TI  - Tail regeneration in Xenopus laevis as a model for understanding tissue repair.
AB  - Augmentation of regenerative ability is a powerful strategy being pursued for the
      biomedical management of traumatic injury, cancer, and degeneration. While
      considerable attention has been focused on embryonic stem cells, it is clear that
      much remains to be learned about how somatic cells may be controlled in the adult
      organism. The tadpole of the frog Xenopus laevis is a powerful model system
      within which fundamental mechanisms of regeneration are being addressed. The
      tadpole tail contains spinal cord, muscle, vasculature, and other terminally
      differentiated cell types and can fully regenerate itself through tissue renewal-
      a process that is most relevant to mammalian healing. Recent insight into this
      process has uncovered fascinating molecular details of how a complex appendage
      senses injury and rapidly repairs the necessary morphology. Here, we review what
      is known about the chemical and bioelectric signals underlying this process and
      draw analogies to evolutionarily conserved pathways in other patterning systems.
      The understanding of this process is not only of fundamental interest for the
      evolutionary and cell biology of morphogenesis, but will also generate
      information that is crucial to the development of regenerative therapies for
      human tissues and organs.

PMID- 18719208
TI  - In vitro performance of nano-heterogeneous dentin adhesive.
AB  - Water is ubiquitous in the mouths of healthy individuals and routinely interferes
      with efforts to bond restorations to dental tissues. Our previous studies using
      tapping-mode atomic force microscopy (TMAFM) have shown that nanophase separation
      is a general feature of cross-linked polymethacrylates photocured in the presence
      of water. To explore the relationship between nanophase separation in dentin
      adhesives and their long-term mechanical properties, we evaluated model adhesives
      after 3 months of aqueous storage. The degree of contrast in the TMAFM phase
      image depended on the formulations used, ranging from 'not observable' to 'very
      strong'. Correspondingly, the mechanical properties of these model adhesives
      varied from 'minimal change' to 'significant depreciation'. The results support
      the hypothesis that a high degree of heterogeneity at the nano-scale is
      associated with poor mechanical durability in these model adhesives.

PMID- 18719210
TI  - Matrix Gla protein inhibition of tooth mineralization.
AB  - Extracellular matrix (ECM) mineralization is regulated by mineral ion
      availability, proteins, and other molecular determinants. To investigate protein
      regulation of mineralization in tooth dentin and cementum, and in alveolar bone,
      we expressed matrix Gla protein (MGP) ectopically in bones and teeth in mice,
      using an osteoblast/odontoblast-specific 2.3-kb Col1a1 promoter. Mandibles were
      analyzed by radiography, micro-computed tomography, light microscopy,
      histomorphometry, and transmission electron microscopy. While bone and tooth ECMs
      were established in the Col1a1-Mgp mice, extensive hypomineralization was
      observed, with values of unmineralized ECM from four- to eight-fold higher in
      dentin and alveolar bone when compared with that in wild-type tissues.
      Mineralization was virtually absent in tooth root dentin and cellular cementum,
      while crown dentin showed "breakthrough" areas of mineralization. Acellular
      cementum was lacking in Col1a1-Mgp teeth, and unmineralized osteodentin formed
      within the pulp. These results strengthen the view that bone and tooth
      mineralization is critically regulated by mineralization inhibitors.

PMID- 18719209
TI  - Mechanotransducers in rat pulpal afferents.
AB  - The hydrodynamic theory suggests that pain associated with stimulation of a
      sensitive tooth ultimately involves mechanotransduction as a consequence of fluid
      movement within exposed dentinal tubules. To determine whether putative
      mechanotransducers could underlie mechanotransduction in pulpal afferents, we
      used a single-cell PCR approach to screen retrogradely labeled pulpal afferents.
      The presence of mRNA encoding BNC-1, ASIC3, TRPV4, TRPA1, the alpha, beta, and
      gamma subunits of ENaC, and the two pore K+ channels (TREK1, TREK2) and TRAAK
      were screened in pulpal neurons from rats with and without pulpal inflammation.
      ASIC3, TRPA1, TREK1, and TREK2 were present in approximately 67%, 64%, 14%, and
      10% of pulpal neurons, respectively. There was no detectable influence of
      inflammation on the proportion of neurons expressing these mechanotransducers.
      Given that the majority of pulpal afferents express ASIC3 and TRPA1, our results
      raise the possibility that these channels may be novel targets for the treatment
      of dentin sensitivity.

PMID- 18719207
TI  - A new inflammatory cytokine on the block: re-thinking periodontal disease and the
      Th1/Th2 paradigm in the context of Th17 cells and IL-17.
AB  - For almost two decades, the Th1/Th2 paradigm has offered a productive conceptual
      framework for investigating the pathogenesis of periodontitis. However, as with
      many other inflammatory diseases, the observed role of T-cell-mediated immunity
      in periodontitis did not readily fit this model. A new subset of CD4+ T-cells was
      recently discovered that explains many of the discrepancies in the classic
      Th1/Th2 model, and has been termed "Th17" based on its secretion of the novel pro
      inflammatory cytokine IL-17. The identification of Th17 cells as a novel effector
      T-cell population compels re-examination of periodontitis in the context of the
      new subset and its signature cytokines. This review aims to offer a clarifying
      insight into periodontal pathogenesis under the extended Th1/Th2/Th17 paradigm,
      and is predicated on the principle that periodontal disease activity is
      determined by a complex interplay between the immune system and periodontal
      pathogens. The re-examination of existing periodontal literature and further
      studies in the light of these new discoveries may help explain how the
      inflammatory response results in damage to the periodontium while generally
      failing to control the pathogens. This knowledge is essential for the development
      of immunomodulatory intervention strategies for fine-tuning the host response to
      maximize the protective and minimize the destructive aspects of the periodontal
      host response. Moreover, with the advent of anti-cytokine biologic drugs that
      target the Th1 and Th17 pathways in autoimmunity, the potential consequences to
      periodontal disease susceptibility in humans need to be understood.

PMID- 18719211
TI  - Combinatorial gene therapy with BMP2/7 enhances cranial bone regeneration.
AB  - BMP2/7 heterodimer expression by adenovirus can stimulate bone formation at
      subcutaneous sites. In the present study, we evaluate whether this approach will
      also promote healing of cranial defects. Adenovirus expressing BMP2 or BMP7
      (AdBMP2, AdBMP7) was titrated to yield equivalent BMP protein levels after
      transduction into murine BLK cells. Analysis of conditioned medium showed that
      BMP2/7 heterodimers have enhanced ability to stimulate alkaline phosphatase and
      Smad 1,5,8 phosphorylation relative to equivalent amounts of BMP2 or BMP7
      homodimers. To measure bone regeneration, we implanted virally transduced BLK
      cells into critical-sized calvarial defects generated in C57BL6 mice. AdBMP2/7
      transduced cells were more effective in healing cranial defects than were cells
      individually transduced with AdBMP2 or BMP7. Dramatic increases in bone volume
      fraction, as measured by microCT, as well as fusion of regenerated bone with the
      defect margins were noted. Thus, the use of gene therapy to express heterodimeric
      BMPs is a promising potential therapy for healing craniofacial bones.

PMID- 18719212
TI  - EGFR in Enamel Matrix Derivative-induced gingival fibroblast mitogenesis.
AB  - We previously reported that EMD (Enamel Matrix Derivative) induces proliferation
      of human gingival fibroblasts via activation of Extracellular Regulated Kinase
      (ERK), and this study assessed the possible mediatory role of EGFR (Epidermal
      Growth Factor Receptor) in this effect. Treatment of gingival fibroblasts with
      EMD resulted in tyrosine phosphorylation of the EGFR, as assessed by
      immunoblotting and ELISA, while EMD-induced ERK activation and thymidine
      incorporation were markedly inhibited (approximately 40-50%) by a specific EGFR
      tyrosine kinase inhibitor. Using appropriate inhibitors, we established that EMD
      induced EGFR activation is largely due to shedding of HB-EGF (Heparin-binding
      EGF) from the cell membrane via a metalloproteinase-mediated process. Finally,
      the addition of PP1, a Src family inhibitor, abrogated both EGFR phosphorylation
      and ERK activation. Taken together, these results indicate that, at least in
      human gingival fibroblasts, EMD-induced ERK activation and proliferation are
      partially due to a Src-dependent, metalloproteinase-mediated transactivation of
      EGFR.

PMID- 18719213
TI  - Induced premaxillary suture fusion: class III malocclusion model.
AB  - The etiology of class III malocclusion remains unknown. The present study
      investigates the relationship between craniofacial morphology and premaxillary
      suture fusion to test the hypothesis that class III malocclusion may be related
      to premaxillary suture fusion. Cyanoacrylate was applied to immobilize the left
      premaxillary suture in the experimental group. Sham surgeries in rats were used
      for controls. Dental impressions and radiographs were taken before and after
      surgery for comparison of craniofacial differences between groups. Overall
      cranial base lengths, craniofacial widths, and craniofacial angulations related
      to the anterior base showed significant differences between groups. At the end of
      the experiment, the growth of the snout in the experimental group was inhibited
      and deviated to the treated side, while no obvious change was seen in the control
      group. The results show that induced premaxillary suture fusion can affect
      craniofacial morphology and indicate that premature premaxillary suture fusion
      may result in class III malocclusion.

PMID- 18719214
TI  - Corticotomy-/osteotomy-assisted tooth movement microCTs differ.
AB  - Corticotomy-assisted and osteotomy-assisted tooth movement involves surgical
      incisions through the alveolar bone. To ascertain whether teeth move by
      distraction osteogenesis or by regional accelerated phenomenon (RAP), we randomly
      assigned 30 Sprague-Dawley rats to one of 5 experimental groups: corticotomy
      alone, corticotomy-assisted tooth movement, osteotomy alone, osteotomy-assisted
      tooth movement, or tooth movement alone. Each animal was imaged by
      microtomography immediately after surgery, after 21 days, and after 2 months.
      After 21 days, regional accelerated phenomenon was observed in the alveolar bone
      of the corticotomy-treated animals and distraction osteogenesis in the osteotomy
      assisted tooth movement animals. Pixel count data were analyzed by nested ANOVA
      for 5 experimental groups, split-mouth controls, 3 levels along the root, and 5
      sites per level. The most demineralized sites after 21 days differed for each of
      the experimental groups. Our study indicates that osteotomies and corticotomies
      induce different alveolar bone reactions, which can be exploited for tooth
      movement.

PMID- 18719215
TI  - Trabecular bone structures in the edentulous diastema of osteoporotic sheep.
AB  - The edentulous ovine diastema represents a suitable region for implantological
      research. Due to distinctive embryonic origin and mechanical loading, the
      edentulous diastema may respond differently to osteoporosis than tooth-bearing
      areas. To test this assumption, we subjected geriatric sheep to ovariectomy,
      calcium-/vitamin-D-restricted diet, and methylprednisolone administration. Adult
      control sheep remained untreated. Structural parameters and bone mineral density
      were determined by microcomputed tomography and conventional computed tomography,
      respectively. We report that the trabecular microstructure in the diastema was
      preserved from catabolic changes. In contrast, the premolar maxillary region of
      osteoporotic sheep had diminished trabecular bone mineral density, with the
      corresponding structural deteriorations. These results suggest that maxillary
      trabecular bone of the edentulous diastema does not respond to catabolic changes
      which occur in the tooth-bearing area in osteoporosis. Our findings imply that
      regional anatomic domains must be considered in the planning of pre-clinical
      studies, taking osteoporotic changes into account.

PMID- 18719216
TI  - Systemic antibiotics and tooth loss in periodontal disease.
AB  - Systemic antibiotics have been recommended for the treatment of destructive
      periodontal disease. Our goal was to relate antibiotic use for medical or dental
      reasons to subsequent tooth loss in a cohort of 12,631 persons with destructive
      periodontal disease. After adjustment for age, smoking, and other confounders,
      the dispensing of antibiotics for 1-13 days, 14-20 days, or 21 or more days was
      not associated with reduced tooth loss [Adjusted rate ratio (RR) = 1.0; 95%
      Confidence Interval (CI) = 0.8-1.1; RR = 1.2; 95% CI = 0.9-1.4, and RR =1.2, 95%
      CI =1.0-1.3, respectively]. Numerous subgroup analyses were consistent with these
      overall null findings, with two exceptions: Longer courses of tetracyclines were
      associated with reduced tooth loss among persons receiving periodontal care, and
      penicillin was associated with reduced tooth loss among persons with more severe
      disease. Long-term, larger randomized trials are needed to provide evidence that
      antibiotics reduce tooth loss when used in the management of destructive
      periodontal disease.

PMID- 18719217
TI  - Stereometric assessment of TMJ space variation by occlusal splints.
AB  - Occlusal splints are used for the management of temporomandibular disorders,
      although their mechanism of action remains controversial. This study investigated
      whether insertion of an occlusal splint leads to condyle-fossa distance changes,
      and to mandibular rotation and/or translation. By combining magnetic resonance
      images with jaw tracking (dynamic stereometry), we analyzed the intra-articular
      distances of 20 human temporomandibular joints (TMJs) before and after insertion
      of occlusal splints of 3 mm thickness in the first molar region. For habitual
      closure, protrusion, and laterotrusion in the contralateral joint, occlusal
      splints led to minor--yet statistically significant--increases of global TMJ
      space and to larger increases at defined condylar areas. Condylar end rotation
      and translation in habitual closure were reduced. Hence, the insertion of a 3-mm
      thick occlusal splint led to a change in the topographical condyle-fossa
      relationship, and therefore to a new distribution of contact areas between joint
      surfaces.

PMID- 18719218
TI  - Obstructive sleep apnea therapy.
AB  - In clinical practice, oral appliances are used primarily for obstructive sleep
      apnea patients who do not respond to continuous positive airway pressure (CPAP)
      therapy. We hypothesized that an oral appliance is not inferior to CPAP in
      treating obstructive sleep apnea effectively. We randomly assigned 103
      individuals to oral-appliance or CPAP therapy. Polysomnography after 8-12 weeks
      indicated that treatment was effective for 39 of 51 persons using the oral
      appliance (76.5%) and for 43 of 52 persons using CPAP (82.7%). For the difference
      in effectiveness, a 95% two-sided confidence interval was calculated. Non
      inferiority of oral-appliance therapy was considered to be established when the
      lower boundary of this interval exceeded -25%. The lower boundary of the
      confidence interval was -21.7%, indicating that oral-appliance therapy was not
      inferior to CPAP for effective treatment of obstructive sleep apnea. However,
      subgroup analysis revealed that oral-appliance therapy was less effective in
      individuals with severe disease (apnea-hypopnea index > 30). Since these people
      could be at particular cardiovascular risk, primary oral-appliance therapy
      appears to be supported only for those with non-severe apnea.

PMID- 18719219
TI  - Changes in women's choice of dress across the ovulatory cycle: naturalistic and
      laboratory task-based evidence.
AB  - The authors tested the prediction that women prefer clothing that is more
      revealing and sexy when fertility is highest within the ovulatory cycle. Eighty
      eight women reported to the lab twice: once on a low-fertility day of the cycle
      and once on a high-fertility day (confirmed using hormone tests). In each
      session, participants posed for full-body photographs in the clothing they wore
      to the lab, and they drew illustrations to indicate an outfit they would wear to
      a social event that evening. Although each data source supported the prediction,
      the authors found the most dramatic changes in clothing choice in the
      illustrations. Ovulatory shifts in clothing choice were moderated by
      sociosexuality, attractiveness, relationship status, and relationship
      satisfaction. Sexually unrestricted women, for example, showed greater shifts in
      preference for revealing clothing worn to the laboratory near ovulation. The
      authors suggest that clothing preference shifts could reflect an increase in
      female-female competition near ovulation.

PMID- 18719220
TI  - The drugs-violence nexus among rural felony probationers.
AB  - Little research has focused on the drugs-violence nexus in rural areas. As such,
      the purpose of this study is to use Goldstein's tripartite conceptual framework
      to examine the relationship between drugs and violence among felony probationers
      in rural Appalachian Kentucky (n = 799). Data on demographics, substance use
      criminal history, and violence were collected between 2001 and 2004 using an
      interviewer-administered questionnaire. Rural probationers are partitioned into
      four groups based on lifetime violent victimization/perpetration experiences: (a)
      neither a perpetrator nor a victim, (b) perpetrator only, (c) victim only, and
      (d) both a perpetrator and a victim. Chi-square analyses indicate substance use,
      and criminal history varies across the four groups. Binary logistic regression
      analyses are used to explore the significant correlates of both perpetration and
      victimization. Multivariate analyses support both the psychopharmacological model
      and the economic compulsive models of perpetration and victimization. Further
      implications of these findings are discussed.

PMID- 18719221
TI  - Examining the relationship between a childhood history of sexual abuse and later
      dissociation, breast-feeding practices, and parenting anxiety.
AB  - The purpose of this study is to compare Mexican American adolescent mothers with
      and without childhood sexual abuse (CSA) histories to examine the influence of
      CSA on dissociation, selection of infant feeding method, and intimate parenting
      anxiety. Participants are 78 English-speaking adolescents between 15 and 19 years
      of age and recruited from the southwestern United States. Nearly one third of the
      sample ( n = 24, 30.77%) reports CSA histories. There is no correlation between
      CSA history and intimate parenting anxiety, no difference between breast-feeding
      and formula-feeding mothers in CSA severity, and intimate parenting anxiety does
      not predict dissociation. These findings are inconsistent with previous research.
      Supportive resources may explain the inconsistency and play a role in adolescent
      mothers' responses to CSA. Further research is necessary to explore these
      possibilities.

PMID- 18719222
TI  - Endogenous regeneration in Parkinson's disease: do we need orthotopic
      dopaminergic neurogenesis?

PMID- 18719223
TI  - Improved granulocyte colony-stimulating factor mobilization of hemopoietic
      progenitors using cytokine combinations in primates.
AB  - Peripheral blood stem cells (PBSCs), usually mobilized with granulocyte colony
      stimulating factor (G-CSF) alone or in combination with chemotherapy, are the
      preferred source of cells for hemopoietic stem cell transplantation. Up to 25% of
      otherwise eligible transplant recipients fail to harvest adequate PBSCs.
      Therefore it is important to investigate existing and novel reagents to improve
      PBSC mobilization. Because of marked interindividual variation in humans, we
      developed a robust nonhuman primate model that allows the direct comparison of
      the efficacy of two PBSC mobilization regimens within the same animal. Using this
      model, we compared pegylated G-CSF (pegG-CSF) with standard G-CSF and compared
      the combination of G-CSF and pegylated megakaryocyte growth and development
      factor (pegMGDF) with G-CSF plus stem cell factor (SCF) by measuring the levels
      of CD34(+) cells, colony-forming cells (CFCs), and SCID repopulating cells (SRCs)
      before and after cytokine administration. Mobilization of CD34(+) cells, CFCs and
      SRCs using pegG-CSF achieved similar levels to those resulting from 5 days of
      standard G-CSF. The combination of G-CSF+pegMGDF mobilized progenitors to levels
      similar to G-CSF+SCF but greater than standard G-CSF for CD34(+) cells and CFC.
      This first direct comparison of PBSC mobilization in individual primates
      demonstrates that peg-G-CSF is equivalent to daily G-CSF and that the addition of
      pegMGDF to G-CSF improves mobilization. In light of the development of new
      thrombopoietin agonists, these data offer the potential for improved stem cell
      mobilization strategies. Disclosure of potential conflicts of interest is found
      at the end of this article.

PMID- 18719224
TI  - Spermatogonial stem cell self-renewal requires OCT4, a factor downregulated
      during retinoic acid-induced differentiation.
AB  - The long-term production of billions of spermatozoa relies on the regulated
      proliferation and differentiation of spermatogonial stem cells (SSCs). To date
      only a few factors are known to function in SSCs to provide this regulation.
      Octamer-4 (OCT4) plays a critical role in pluripotency and cell survival of
      embryonic stem cells and primordial germ cells; however, it is not known whether
      it plays a similar function in SSCs. Here, we show that OCT4 is required for SSC
      maintenance in culture and for colonization activity following cell
      transplantation, using lentiviral-mediated short hairpin RNA expression to knock
      down OCT4 in an in vitro model for SSCs ("germline stem" [GS] cells). Expression
      of promyelocytic leukemia zinc-finger (PLZF), a factor known to be required for
      SSC self-renewal, was not affected by OCT4 knockdown, suggesting that OCT4 does
      not function upstream of PLZF. In addition to developing a method to test
      specific gene function in GS cells, we demonstrate that retinoic acid (RA)
      triggers GS cells to shift to a differentiated, premeiotic state lacking OCT4 and
      PLZF expression and colonization activity. Our data support a model in which OCT4
      and PLZF maintain SSCs in an undifferentiated state and RA triggers
      spermatogonial differentiation through the direct or indirect downregulation of
      OCT4 and PLZF. The current study has important implications for the future use of
      GS cells as an in vitro model for spermatogonial stem cell biology or as a source
      of embryonic stem-like cells. Disclosure of potential conflicts of interest is
      found at the end of this article.

PMID- 18719225
TI  - Enrichment and differentiation of human germ-like cells mediated by feeder cells
      and basic fibroblast growth factor signaling.
AB  - Human embryonic stem cells (hESCs) have recently demonstrated the potential for
      differentiation into germ-like cells in vitro. This provides a novel model for
      understanding human germ cell development and human infertility. Mouse embryonic
      fibroblast (MEF) feeders and basic fibroblast growth factor (bFGF) are two
      sources of signaling that are essential for primary culture of germ cells, yet
      their role has not been examined in the derivation of germ-like cells from hESCs.
      Here protein and gene expression demonstrated that both MEF feeders and bFGF can
      significantly enrich germ cell differentiation from hESCs. Under enriched
      differentiation conditions, flow cytometry analysis proved 69% of cells to be
      positive for DDX4 and POU5F1 protein expression, consistent with the germ cell
      lineage. Importantly, removal of bFGF from feeder-free cultures resulted in a 50%
      decrease in POU5F1- and DDX4-positive cells. Quantitative reverse transcription
      polymerase chain reaction analysis established that bFGF signaling resulted in an
      upregulation of genes involved in germ cell differentiation with or without
      feeders; however, feeder conditions caused significant upregulation of
      premigratory/migratory (Ifitm3, DAZL, NANOG, and POU5F1) and postmigratory
      (PIWIL2, PUM2) genes, along with the meiotic markers SYCP3 and MLH1. After
      further differentiation, >90% of cells expressed the meiotic proteins SYCP3 and
      MLH1. This is the first demonstration that signaling from MEF feeders and bFGF
      can induce a highly enriched population of germ-like cells derived from hESCs,
      thus providing a critically needed model for further investigation of human germ
      cell development and signaling. Disclosure of potential conflicts of interest is
      found at the end of this article.

PMID- 18719226
TI  - Human amniotic fluid stem cells can integrate and differentiate into epithelial
      lung lineages.
AB  - A new source of stem cells has recently been isolated from amniotic fluid; these
      amniotic fluid stem cells have significant potential for regenerative medicine.
      These cells are multipotent, showing the ability to differentiate into cell types
      from each embryonic germ layer. We investigated the ability of human amniotic
      fluid stem cells (hAFSC) to integrate into murine lung and to differentiate into
      pulmonary lineages after injury. Using microinjection into cultured mouse
      embryonic lungs, hAFSC can integrate into the epithelium and express the early
      human differentiation marker thyroid transcription factor 1 (TTF1). In adult nude
      mice, following hyperoxia injury, tail vein-injected hAFSC localized in the
      distal lung and expressed both TTF1 and the type II pneumocyte marker surfactant
      protein C. Specific damage of Clara cells through naphthalene injury produced
      integration and differentiation of hAFSC at the bronchioalveolar and bronchial
      positions with expression of the specific Clara cell 10-kDa protein. These
      results illustrate the plasticity of hAFSC to respond in different ways to
      different types of lung damage by expressing specific alveolar versus bronchiolar
      epithelial cell lineage markers, depending on the type of injury to recipient
      lung. Disclosure of potential conflicts of interest is found at the end of this
      article.

PMID- 18719228
TI  - Point:counterpoint: respiratory sinus arrhythmia is due to a central mechanism
      vs. respiratory sinus arrhythmia is due to the baroreflex mechanism.

PMID- 18719227
TI  - Modulation of inflammatory responses after global ischemia by transplanted
      umbilical cord matrix stem cells.
AB  - Rat umbilical cord matrix (RUCM) cells are stem-cell-like cells and have been
      shown to reduce neuronal loss in the selectively vulnerable brain regions after
      cardiac arrest (CA). Here, we investigate whether this protection is mediated by
      the RUCM cells' modulation of the postischemia inflammation responses, which have
      long been implicated as a secondary mechanism of injury following ischemia. Brain
      sections were examined immunohistochemically for glial fibrillary acidic protein
      (GFAP), vimentin, and nestin as markers for astroglia and reactive astrogliosis,
      Ricinus Communis Agglutinin-1 (RCA-1) as a marker for microglia, and Ki67 as a
      marker for cell proliferation. Rats were randomly assigned to six experimental
      groups: (1) 8-minute CA without treatment, (2) 8-minute CA pre-treated with
      culture medium injection, (3) 8-minute CA pre-treated with RUCM cells, (4) sham
      operated CA, (5) medium injection without CA, and (6) RUCM cell transplantation
      without CA. Groups 1-3 have significantly higher Ki67(+) cell counts and higher
      GFAP(+) immunoreactivity in the hippocampal Cornu Ammonis layer 1 (CA1) region
      compared to groups 4-6, irrespective of treatment. Groups 1 and 2 have highly
      elevated GFAP(+), vimentin(+), and nestin(+) immunoreactivity, indicating
      reactive astrogliosis. Strikingly, RUCM cell treatment nearly completely
      inhibited the appearance of vimentin(+) and greatly reduced nestin(+) reactive
      astrocytes. RUCM cell treatment also greatly reduced RCA-1 staining, which is
      found to strongly correlate with the neuronal loss in the CA1 region. Our study
      indicates that treatment with stem-cell-like RUCM cells modulates the
      inflammatory response to global ischemia and renders neuronal protection by
      preventing permanent damage to the selectively vulnerable astrocytes in the CA1
      region. Disclosure of potential conflicts of interest is found at the end of this
      article.

PMID- 18719229
TI  - How do we solve the puzzle of unintended consequences of inflammation?
      Systematically.

PMID- 18719230
TI  - Use of mean airspace chord length to assess emphysema.

PMID- 18719231
TI  - Changes in vascular and cardiac function after prolonged strenuous exercise in
      humans.
AB  - Prolonged exercise has been shown to result in an acute depression in cardiac
      function. However, little is known about the effect of this type of exercise on
      vascular function. Therefore, the purpose of the present study was to investigate
      the impact of an acute bout of prolonged strenuous exercise on vascular and
      cardiac function and the appearance of biomarkers of cardiomyocyte damage in 15
      male (32 +/- 10 yr) nonelite runners. The subjects were tested on two occasions,
      the day before and within an hour of finishing the London marathon (229 +/- 38
      min). Function of the brachial and femoral arteries was determined using flow
      mediated dilatation (FMD). Echocardiographic assessment of cardiac strain, strain
      rate, tissue velocities, and flow velocities during diastole and systole were
      also obtained. Venous blood samples were taken for later assessment of cardiac
      troponin I (cTnI), a biomarker of cardiomyocyte damage. Completion of the
      marathon resulted in a depression in femoral (P = 0.04), but not brachial (P =
      0.96), artery FMD. There was no change, pre- vs. postmarathon, in vascular shear,
      indicating that the impaired femoral artery function was not related to
      hemodynamic changes. The ratio of peak early to atrial radial strain rate, a
      measure of left ventricular diastolic function, was reduced postmarathon (P =
      0.006). Postrace cTnI was elevated in 12 of 13 runners, with levels above the
      recognized clinical threshold for damage in 7 of these. In conclusion, when taken
      together, these data suggest a transient depression in cardiac and leg vascular
      function following prolonged intensive exercise.

PMID- 18719232
TI  - Respiratory-related evoked potential measures of respiratory sensory gating.
AB  - The purpose of this study was to demonstrate a neural respiratory gating system
      using a paired stimuli paradigm. The N1 peak of the respiratory-related evoked
      potential (RREP) represents early perceptual processing of respiratory sensory
      information. This is similar to the N100 peak shown with tactile sensation, where
      the second peak amplitude (S2) of the N100 peak from the somatosensory evoked
      potential (SEP) was smaller than the first peak amplitude (S1) when the stimuli
      were presented 500 ms apart. We hypothesized that paired inspiratory occlusions
      would result in a reduced amplitude of the S2 N1 RREP peak amplitude, indicating
      respiratory central neural gating. Twenty healthy subjects (10 men and 10 women;
      25.8 +/- 6.5 yr old) completed the paired inspiratory occlusion (RREP) trial.
      Thirteen of the subjects also completed the paired mouth air puffs [mouth-evoked
      potential (MEP) trial], and the paired hand air puffs (SEP) trial. All paired
      presentations were separated by 500 ms. The N1 peak amplitudes of the RREP trial
      and the N100 peak amplitudes of the MEP and SEP trials for S1 and S2 and the
      S2/S1 ratios were determined. The S1 RREP N1 peak amplitude was significantly
      greater than S2, and the S2/S1 ratio was 0.43. The S1 MEP and SEP N100 peak
      amplitudes were significantly greater than S2, and the N100 ratio was 0.49 and
      0.49, respectively. These results are consistent with central neural gating of
      respiratory afferent input. The RREP gating response is similar to somatosensory
      mechanoreceptor gating.

PMID- 18719234
TI  - Aging affects vascular structure and function in a limb-specific manner.
AB  - The limb-specific effects of aging upon vessel structure and function are not
      well understood. Consequently, in 12 young (26 +/- 2 yr) and 12 old (72 +/- 1 yr)
      healthy subjects, we utilized ultrasound Doppler to evaluate intima-media
      thickness (IMT), ischemic reperfusion, and flow-mediated dilation (FMD) following
      (5 min) suprasystolic cuff occlusion in both the arm [brachial artery (BA)] and
      the leg [popliteal artery (PA)]. Structural measurements, whether normalized for
      vessel size or not, revealed a greater IMT in both the BA and PA with age (young:
      BA 0.028 +/- 0.001 and PA 0.046 +/- 0.003 cm, old: BA 0.039 +/- 0.002 and PA
      0.073 +/- 0.005 cm; P < 0.05). Ischemic reperfusion revealed a similar pattern as
      IMT in terms of limb and age-related differences. There was an age-related
      attenuation in both BA FMD (old: 38% smaller BA FMD compared with young) and PA
      FMD (old: 71% smaller PA FMD compared with young). However, when this percent
      change was normalized for shear rate, only the PA FMD of the old group was still
      significantly attenuated (old: 41% smaller PA FMD/shear rate compared with
      young). Together, the finding of differential structural and functional
      parameters in the arms and legs of healthy young people, and the somewhat
      negative findings that are specific to the legs of otherwise healthy older people
      (greater IMT and attenuated FMD), support and may help to better understand the
      increased propensity to develop a vascular pathology in the legs with age.

PMID- 18719233
TI  - Arginase and vascular aging.
AB  - Vascular and associated ventricular stiffness is one of the hallmarks of the
      aging cardiovascular system. Both an increase in reactive oxygen species
      production and a decrease in nitric oxide (NO) bioavailability contribute to the
      endothelial dysfunction that underlies this vascular stiffness, independent of
      other age-related vascular pathologies such as atherosclerosis. The
      activation/upregulation of arginase appears to be an important contributor to age
      related endothelial dysfunction by a mechanism that involves substrate (L
      arginine) limitation for NO synthase (NOS) 3 and therefore NO synthesis. Not only
      does this lead to impaired NO production but also it contributes to the enhanced
      production of reactive oxygen species by NOS. Although arginase abundance is
      increased in vascular aging models, it appears that posttranslational
      modification by S-nitrosylation of the enzyme enhances its activity as well. The
      S-nitrosylation is mediated by the induction of NOS2 in the endothelium.
      Furthermore, arginase activation contributes to aging-related vascular changes by
      mechanisms that are not directly related to changes in NO signaling, including
      polyamine-dependent vascular smooth muscle proliferation and collagen synthesis.
      Taken together, arginase may represent an as yet elusive target for the
      modification of age-related vascular and ventricular stiffness contributing to
      cardiovascular morbidity and mortality.

PMID- 18719235
TI  - Hemodynamic impact of mitral prosthesis-patient mismatch on pulmonary
      hypertension: an in silico study.
AB  - Recent clinical studies reported that prosthesis-patient mismatch (PPM) becomes
      clinically relevant when the effective orifice area (EOA) indexed by the body
      surface area (iEOA) is <1.2-1.25 cm(2)/m(2). To examine the effect of PPM on
      transmitral pressure gradient and left atrial (LA) and pulmonary arterial (PA)
      pressures and to validate the PPM cutoff values, we used a lumped model to
      compute instantaneous pressures, volumes, and flows into the left-sided heart and
      the pulmonary and systemic circulations. We simulated hemodynamic conditions at
      low cardiac output, at rest, and at three levels of exercise. The iEOA was varied
      from 0.44 to 1.67 cm(2)/m(2). We normalized the mean pressure gradient by the
      square of mean mitral flow indexed by the body surface area to determine at which
      cutoff values of iEOA the impact of PPM becomes hemodynamically significant. In
      vivo data were used to validate the numerical study, which shows that small
      values of iEOA (severe PPM) induce high PA pressure (residual PA hypertension)
      and contribute to its nonnormalization following a valve replacement, providing a
      justification for implementation of operative strategies to prevent PPM.
      Furthermore, we emphasize the major impact of pulmonary resistance and compliance
      on PA pressure. The model suggests also that the cutoff iEOA that should be used
      to define PPM at rest in the mitral position is approximately 1.16 cm(2)/m(2). At
      higher levels of exercise, the threshold for iEOA is rather close to 1.5
      cm(2)/m(2). Severe PPM should be considered when iEOA is <0.94 cm(2)/m(2) at
      rest.

PMID- 18719236
TI  - Humans adjust control to initial squat depth in vertical squat jumping.
AB  - The purpose of this study was to gain insight into the control strategy that
      humans use in jumping. Eight male gymnasts performed vertical squat jumps from
      five initial postures that differed in squat depth (P1-P5) while kinematic data,
      ground reaction forces, and electromyograms (EMGs) of leg muscles were collected;
      the latter were rectified and smoothed to obtain SREMGs. P3 was the preferred
      initial posture; in P1, P2, P4, and P5 height of the mass center was +13, +7, -7
      and -14 cm, respectively, relative to that in P3. Furthermore, maximum-height
      jumps from the initial postures observed in the subjects were simulated with a
      model comprising four body segments and six Hill-type muscles. The only input was
      the onset of stimulation of each of the muscles (Stim). The subjects were able to
      perform well-coordinated squat jumps from all postures. Peak SREMG levels did not
      vary among P1-P5, but SREMG onset of plantarflexors occurred before that of
      gluteus maximus in P1 and > 90 ms after that in P5 (P < 0.05). In the simulation
      study, similar systematic shifts occurred in Stim onsets across the optimal
      control solutions for jumps from P1-P5. Because the adjustments in SREMG onsets
      to initial posture observed in the subjects were very similar to the adjustments
      in optimal Stim onsets of the model, it was concluded that the SREMG adjustments
      were functional, in the sense that they contributed to achieving the greatest
      jump height possible from each initial posture. For the model, we were able to
      develop a mapping from initial posture to Stim onsets that generated successful
      jumps from P1-P5. It appears that to explain how subjects adjust their control to
      initial posture there is no need to assume that the brain contains an internal
      dynamics model of the musculoskeletal system.

PMID- 18719237
TI  - 3D 3He diffusion MRI as a local in vivo morphometric tool to evaluate
      emphysematous rat lungs.
AB  - In this work, we investigate (3)He magnetic resonance imaging as a noninvasive
      morphometric tool to assess emphysematous disease state on a local level.
      Emphysema was induced intratracheally in rats with 25 U/100 g body wt of porcine
      pancreatic elastase dissolved in 200 microl saline. Rats were then paired with
      saline-dosed controls. Nine three-dimensional (3D) (3)He diffusion-weighted
      images were acquired at 1, 2, or 3 wk postdose, after which the lungs were
      harvested and prepared for histological analysis. Recently introduced indexes
      sensitive to the heterogeneity of the air space size distribution were
      calculated. These indexes, D(1) and D(2), were derived from the moments of the
      mean equivalent airway diameters. Averaged over the entire lung, it is shown that
      the average (3)He diffusivity (D(ave)) correlates well with histology (R = 0.85,
      P < 0.0001). By matching small (0.046 cm(2)) regions in (3)He images with
      corresponding regions in histological slices, D(ave) correlates significantly
      with both D(1) and D(2) (R = 0.88 and R = 0.90, respectively, with P < 0.0001).
      It is concluded that (3)He MRI is a viable noninvasive morphometric tool for
      localized in vivo emphysema assessment.

PMID- 18719238
TI  - Predicting diffusive alveolar oxygen transfer from carbon monoxide-diffusing
      capacity in exercising foxhounds.
AB  - Although lung diffusing capacity for carbon monoxide (DL(CO)) is a widely used
      test of diffusive O2 transfer, few studies have directly related DL(CO) to O2
      diffusing capacity (DL(O2)); none has used the components of Dl(CO), i.e.,
      conductance of alveolar membrane and capillary blood, to predict DL(O2) from rest
      to exercise. To understand the relationship between DL(CO) and DL(O2) at matched
      levels of cardiac output, we analyzed cumulative data from rest to heavy exercise
      in 43 adult dogs, with normal lungs or reduced lung capacity following lung
      resection, that were studied by two techniques. 1) A rebreathing (RB) technique
      was used to measure Dl(CO) and pulmonary blood flow at two O2 tensions,
      independent of O2 exchange. DL(CO) was partitioned into CO-diffusing capacity of
      alveolar membrane and pulmonary capillary blood volume using the Roughton-Forster
      equation and converted into an equivalent DL(O2), [DL(O2)(RB)]. 2) A multiple
      inert-gas elimination technique (MIGET) was used to measure ventilation-perfusion
      distributions, O2 and CO2 exchange under hypoxia, to derive DL(O2)
      [DL(O2)(MIGET)] by the Lilienthal-Riley technique and Bohr integration. For
      direct comparisons, DL(O2)(RB) was interpolated to the cardiac output measured by
      the Fick principle corresponding to DL(O2)(MIGET). The DL(O2)-to-DL(CO) ratio
      averaged 1.61. Correlation between DL(O2)(RB) and DL(O2)(MIGET) was similar in
      normal and post-resection groups. Overall, DL(O2)(MIGET) = 0.975 DL(O2)(RB); mean
      difference between the two techniques was under 5% for both animal groups. We
      conclude that, despite various uncertainties inherent in these two disparate
      methods, the Roughton-Forster equation adequately predicts diffusive O2 transfer
      from rest to heavy exercise in canines with normal, as well as reduced, lung
      capacities.

PMID- 18719239
TI  - Effects of L-lactate and D-mannitol on gamma-hydroxybutyrate toxicokinetics and
      toxicodynamics in rats.
AB  - Overdoses of gamma-hydroxybutyrate (GHB), a drug of abuse, result in coma,
      respiratory arrest, and death. The objective of this study was to evaluate a
      potential GHB detoxification strategy by inhibiting the monocarboxylate
      transporter (MCT)-mediated renal reabsorption of GHB in rats, using the MCT
      substrate L-lactate. The use of the osmotic diuretic D-mannitol alone or combined
      with L-lactate was also explored. GHB (208 mg/h/kg) was infused i.v. for 3 h in
      the absence or presence of L-lactate (60.5, 121, and 302.5 mg h(-1) kg(-1)), D
      mannitol (0.5 g/kg), or L-lactate (60.5 mg h(-1) kg(-1)) combined with D-mannitol
      (0.5 g/kg). GHB in plasma and urine samples was determined along with blood pH,
      electrolytes, glucose, and L-lactate. Administration of L-lactate, or the
      combination of L-lactate and D-mannitol, but not D-mannitol alone, significantly
      increased the renal and total clearances of GHB in rats. Blood pH and electrolyte
      concentrations exhibited small changes with GHB, GHB/lactate, and GHB/mannitol
      treatments, although most values remained within their normal range. The
      concomitant administration of lactated Ringer's solution (28 mM L-lactate) at 300
      mul/min with mannitol (0.5 g/kg) resulted in a significant increase in GHB
      clearance and a decrease in sleep time after an i.v. dose of 1 g/kg. Overall, our
      results indicated the following: 1) the use of the MCT inhibitor L-lactate can
      increase the renal and total clearances of GHB, and 2) the combination of
      lactated Ringer's solution and D-mannitol significantly alters GHB toxicokinetics
      and toxicodynamics and represents a potential clinical detoxification strategy
      for the treatment of GHB overdoses.

PMID- 18719240
TI  - The configuration of the 17-hydroxy group variably influences the glucuronidation
      of beta-estradiol and epiestradiol by human UDP-glucuronosyltransferases.
AB  - The glucuronidation of 17beta-estradiol (beta-estradiol) and 17alpha-estradiol
      (epiestradiol) was studied to elucidate how the orientation of the 17-OH group
      affects conjugation at the 3-OH or the 17-OH of either diastereomer. Recombinant
      human UDP-glucuronosyltransferases (UGTs) UGT1A1, UGT1A3, UGT1A7, UGT1A8, and
      UGT1A10 conjugated one or both diastereomers, mainly at the 3-OH. The activity of
      UGT1A4 was low and unique because it was directed merely toward the 17-OH of both
      aglycones. UGT1A10 exhibited particularly high estradiol glucuronidation
      activity, the rate and affinity of which were significantly higher in the case of
      beta-estradiol than with epiestradiol. UGT1A9 did not catalyze estradiol
      glucuronidation, but UGT1A9-catalyzed scopoletin glucuronidation was
      competitively inhibited by beta-estradiol. UGT2B4, UGT2B7, and UGT2B17
      exclusively conjugated the estradiols at the 17-OH position in a highly
      stereoselective fashion. UGT2B4 was specific for epiestradiol; UGT2B7
      glucuronidated both diastereomers, with high affinity for epiestradiol, whereas
      UGT2B17 only glucuronidated beta-estradiol. UGT2B15 glucuronidated both
      estradiols at the 3-OH, with a strong preference for epiestradiol. Human UGT2A1
      and UGT2A2 glucuronidated both diastereoisomers at both hydroxyl groups.
      Microsomal studies revealed that human liver mainly yielded epiestradiol 17-O
      glucuronide, and human intestine primarily yielded beta-estradiol 3-O
      glucuronide, whereas rat liver preferentially formed beta-estradiol 17-O
      glucuronide. Of the three recombinant rat UGTs that were examined in this study,
      rUGT2B1 was specific for the 17-OH of beta-estradiol, rUGT2B2 did not catalyze
      estradiol glucuronidation, whereas rUGT2B3 exhibited high activity toward the 17
      OH in both diastereoisomers. The results show that although many UGTs can
      catalyze estradiol glucuronidation, there are marked differences in their
      kinetics, regioselectivity, and stereoselectivity.

PMID- 18719241
TI  - Apparent differences in mechanisms of harmol sulfate biliary excretion in mice
      and rats.
AB  - Previous experiments demonstrated that the biliary excretion of harmol sulfate
      (HS) was mediated by breast cancer resistance protein (Bcrp) and not by multidrug
      resistance-associated protein (Mrp)2 or P-glycoprotein in mice. However, recent
      reports suggested that species differences in hepatic canalicular transport
      mechanisms for a given substrate exist between mice and rats. In the present
      study, biliary excretion of HS was examined in perfused livers from mice and rats
      in the absence or presence of the P-glycoprotein and Bcrp inhibitor N-(4-[2
      (1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5
      methoxy-9-oxo-4-acridine carboxamide (GF120918). As expected, in mouse liver
      perfusions, the biliary excretion of HS was decreased approximately 3.5-fold by
      GF120918, consistent with previous reports of Bcrp-mediated HS biliary excretion.
      However, despite sufficient hepatic unbound concentrations of GF120918 to achieve
      extensive inhibition of Bcrp, the biliary excretion of HS was not decreased
      significantly in wild-type (50 +/- 12 versus 41 +/- 6%) or TR(-) (18 +/- 2 versus
      16 +/- 3%) Wistar rats. In summary, biliary excretion of HS was mediated by a
      GF120918-sensitive mechanism in mice, previously elucidated as Bcrp. In contrast,
      the pathway responsible for HS biliary excretion in rats was not impaired by
      GF120918. Thus, transport mechanism(s) responsible for harmol sulfate biliary
      excretion appear to differ between mice and rats.

PMID- 18719242
TI  - Identification of specific let-7 microRNA binding complexes in Caenorhabditis
      elegans.
AB  - Little is known about the protein complexes required for microRNA formation and
      function. Here we used native gel electrophoresis to identify miRNA
      ribonucleoprotein complexes (miRNPs) in Caenorhabditis elegans. Our data reveal
      multiple distinct miRNPs that assemble on the let-7 miRNA in vitro. The formation
      of these complexes is affected but not abolished by alg-1 or alg-2 null
      mutations. The largest complex (M*) with an estimated molecular mass of >669 kDa
      cofractionates with the known RISC factors ALG-1, VIG-1, and TSN-1. The M*
      complex and two complexes, M3 and M4, with similar molecular weights of
      approximately 500 kDa, also assemble on all other miRNAs used in our experiments.
      Two smaller complexes, M1 (approximately 160 kDa) and M2 (approximately 250 kDa),
      assemble on the members of the let-7 miRNAs family but not lin-4 or mir-234, and
      their formation is highly dependent on specific sequences in the 5' seed region
      of let-7. Moreover, an unidentified protein, p40, which only appears in the M1
      and M2 complexes, was detected by UV triggered cross-linking to let-7 but not to
      lin-4. The cross-linking of p40 to let-7 is also dependent on the let-7 sequence.
      Another unidentified protein, p13, is detected in all let-7 binding complexes and
      lin-4 cross-linked products. Our data suggest that besides being present in
      certain large miRNPs with sizes similar to reported RISC, the let-7 miRNA also
      assembles with specific binding proteins and forms distinct small complexes.

PMID- 18719243
TI  - tRNA cleavage is a conserved response to oxidative stress in eukaryotes.
AB  - Recent results have identified a diversity of small RNAs in a wide range of
      organisms. In this work, we demonstrate that Saccharomyces cerevisiae contains a
      small RNA population consisting primarily of tRNA halves and rRNA fragments. Both
      5' and 3' fragments of tRNAs are detectable by Northern blot analysis, suggesting
      a process of endonucleolytic cleavage. tRNA and rRNA fragment production in yeast
      is most pronounced during oxidative stress conditions, especially during entry
      into stationary phase. Similar tRNA fragments are also observed in human cell
      lines and in plants during oxidative stress. These results demonstrate that tRNA
      cleavage is a conserved aspect of the response to oxidative stress.

PMID- 18719244
TI  - A cell-based screen for splicing regulators identifies hnRNP LL as a distinct
      signal-induced repressor of CD45 variable exon 4.
AB  - The human CD45 gene encodes a protein-tyrosine phosphatase that exhibits
      differential isoform expression in resting and activated T cells due to
      alternative splicing of three variable exons. Previously, we have used
      biochemical methods to identify two regulatory proteins, hnRNP L and PSF, which
      contribute to the activation-induced skipping of CD45 via the ESS1 regulatory
      element in variable exon 4. Here we report the identification of a third CD45
      regulatory factor, hnRNP L-like (hnRNP LL), via a cell-based screen for clonal
      variants that exhibit an activation-like phenotype of CD45 splicing even under
      resting conditions. Microarray analysis of two splicing-altered clones revealed
      increased expression of hnRNP LL relative to wild-type cells. We further
      demonstrate that both the expression of hnRNP LL protein and its binding to ESS1
      are up-regulated in wild-type cells upon activation. Forced overexpression of
      hnRNP LL in wild-type cells results in an increase in exon repression, while
      knock-down of hnRNP LL eliminates activation-induced exon skipping.
      Interestingly, analysis of the binding of hnRNP L and hnRNP LL to mutants of ESS1
      reveals that these proteins have overlapping, but distinct binding requirements.
      Together, these data establish that hnRNP LL plays a critical and unique role in
      the signal-induced regulation of CD45 and demonstrate the utility of cell-based
      screens for the identification of novel splicing regulatory factors.

PMID- 18719245
TI  - C. elegans and H. sapiens mRNAs with edited 3' UTRs are present on polysomes.
AB  - Adenosine deaminases that act on RNA (ADARs) are editing enzymes that convert
      adenosine to inosine in double-stranded RNA (dsRNA). ADARs sometimes target
      codons so that a single mRNA yields multiple protein isoforms. However, ADARs
      most often target noncoding regions of mRNAs, such as untranslated regions
      (UTRs). To understand the function of extensive double-stranded 3' UTR
      structures, and the inosines within them, we monitored the fate of reporter and
      endogenous mRNAs that include structured 3' UTRs in wild-type Caenorhabditis
      elegans and in strains with mutations in the ADAR genes. In general, we saw
      little effect of editing on stability or translatability of mRNA, although in one
      case an ADR-1 dependent effect was observed. Importantly, whereas previous
      studies indicate that inosine-containing RNAs are retained in the nucleus, we
      show that both C. elegans and Homo sapiens mRNAs with edited, structured 3' UTRs
      are present on translating ribosomes.

PMID- 18719246
TI  - Site-specific crosslinking of human microRNPs to RNA targets.
AB  - MicroRNAs (miRNAs) regulate the expression of numerous genes and are implicated
      in the pathogenesis of many human diseases. miRNAs act as specificity
      determinants to guide deposition of microRNPs (miRNPs) onto miRNA recognition
      elements (MREs) that are found in mRNA targets. We have adapted a site-specific
      crosslinking approach, previously used in the analysis of splicing, to
      interrogate protein factors that physically associate with MREs in human cells.
      We find that Ago proteins are the only proteins that bind to the MRE in a miRNA
      dependent manner. Our method may be used in various experimental systems to
      analyze protein factors that influence MRE accessibility by miRNAs and the
      composition of MRE-bound miRNPs.

PMID- 18719249
TI  - Quantum communication with zero-capacity channels.
AB  - Communication over a noisy quantum channel introduces errors in the transmission
      that must be corrected. A fundamental bound on quantum error correction is the
      quantum capacity, which quantifies the amount of quantum data that can be
      protected. We show theoretically that two quantum channels, each with a
      transmission capacity of zero, can have a nonzero capacity when used together.
      This unveils a rich structure in the theory of quantum communications, implying
      that the quantum capacity does not completely specify a channel's ability to
      transmit quantum information.

PMID- 18719247
TI  - lsm1 mutations impairing the ability of the Lsm1p-7p-Pat1p complex to
      preferentially bind to oligoadenylated RNA affect mRNA decay in vivo.
AB  - The poly(A) tail is a crucial determinant in the control of both mRNA translation
      and decay. Poly(A) tail length dictates the triggering of the degradation of the
      message body in the major 5' to 3' and 3' to 5' mRNA decay pathways of
      eukaryotes. In the 5' to 3' pathway oligoadenylated but not polyadenylated mRNAs
      are selectively decapped in vivo, allowing their subsequent degradation by 5' to
      3' exonucleolysis. The conserved Lsm1p-7p-Pat1p complex is required for normal
      rates of decapping in vivo, and the purified complex exhibits strong binding
      preference for oligoadenylated RNAs over polyadenylated or unadenylated RNAs in
      vitro. In the present study, we show that two lsm1 mutants produce mutant
      complexes that fail to exhibit such higher affinity for oligoadenylated RNA in
      vitro. Interestingly, these mutant complexes are normal with regard to their
      integrity and retain the characteristic RNA binding properties of the wild-type
      complex, namely, binding near the 3'-end of the RNA, having higher affinity for
      unadenylated RNAs that carry U-tracts near the 3'-end over those that do not and
      exhibiting similar affinities for unadenylated and polyadenylated RNAs. Yet,
      these lsm1 mutants exhibit a strong mRNA decay defect in vivo. These results
      underscore the importance of Lsm1p-7p-Pat1p complex-mRNA interaction for mRNA
      decay in vivo and imply that the oligo(A) tail mediated enhancement of such
      interaction is crucial in that process.

PMID- 18719250
TI  - Coupled superconducting and magnetic order in CeCoIn5.
AB  - Strong magnetic fluctuations can provide a coupling mechanism for electrons that
      leads to unconventional superconductivity. Magnetic order and superconductivity
      have been found to coexist in a number of magnetically mediated superconductors,
      but these order parameters generally compete. We report that close to the upper
      critical field, CeCoIn5 adopts a multicomponent ground state that simultaneously
      carries cooperating magnetic and superconducting orders. Suppressing
      superconductivity in a first-order transition at the upper critical field leads
      to the simultaneous collapse of the magnetic order, showing that
      superconductivity is necessary for the magnetic order. A symmetry analysis of the
      coupling between the magnetic order and the superconducting gap function suggests
      a form of superconductivity that is associated with a nonvanishing momentum.

PMID- 18719248
TI  - Interactions between eIF4AI and its accessory factors eIF4B and eIF4H.
AB  - Ribonucleoprotein complexes (RNP) remodeling by DEAD-box proteins is required at
      all stages of cellular RNA metabolism. These proteins are composed of a core
      helicase domain lacking sequence specificity; flanking protein sequences or
      accessory proteins target and affect the core's activity. Here we examined the
      interaction of eukaryotic initiation factor 4AI (eIF4AI), the founding member of
      the DEAD-box family, with two accessory factors, eIF4B and eIF4H. We find that
      eIF4AI forms a stable complex with RNA in the presence of AMPPNP and that eIF4B
      or eIF4H can add to this complex, also dependent on AMPPNP. For both accessory
      factors, the minimal stable complex with eIF4AI appears to have 1:1 protein
      stoichiometry. However, because eIF4B and eIF4H share a common binding site on
      eIF4AI, their interactions are mutually exclusive. The eIF4AI:eIF4B and
      eIF4AI:eIF4H complexes have the same RNase resistant footprint as does eIF4AI
      alone (9-10 nucleotides [nt]). In contrast, in a selective RNA binding
      experiment, eIF4AI in complex with either eIF4B or eIF4H preferentially bound
      RNAs much longer than those bound by eIF4AI alone (30-33 versus 17 nt,
      respectively). The differences between the RNase resistant footprints and the
      preferred RNA binding site sizes are discussed, and a model is proposed in which
      eIF4B and eIF4H contribute to RNA affinity of the complex through weak
      interactions not detectable in structural assays. Our findings mirror and expand
      on recent biochemical and structural data regarding the interaction of eIF4AI's
      close relative eIF4AIII with its accessory protein MLN51.

PMID- 18719253
TI  - Science and security, again.

PMID- 18719251
TI  - Chemokine signaling controls endodermal migration during zebrafish gastrulation.
AB  - Directed cell movements during gastrulation establish the germ layers of the
      vertebrate embryo and coordinate their contributions to different tissues and
      organs. Anterior migration of the mesoderm and endoderm has largely been
      interpreted to result from epiboly and convergent-extension movements that drive
      body elongation. We show that the chemokine Cxcl12b and its receptor Cxcr4a
      restrict anterior migration of the endoderm during zebrafish gastrulation,
      thereby coordinating its movements with those of the mesoderm. Depletion of
      either gene product causes disruption of integrin-dependent cell adhesion,
      resulting in separation of the endoderm from the mesoderm; the endoderm then
      migrates farther anteriorly than it normally would, resulting in bilateral
      duplication of endodermal organs. This process may have relevance to human
      gastrointestinal bifurcations and other organ defects.

PMID- 18719254
TI  - Anthrax investigation. FBI discusses microbial forensics--but key questions
      remain unanswered.

PMID- 18719255
TI  - Anthrax investigation. Six anthrax science questions the FBI has yet to answer.

PMID- 18719256
TI  - Tectonics. Pumping up the Tibetan Plateau from the far Pacific Ocean.

PMID- 18719252
TI  - High-quality binary protein interaction map of the yeast interactome network.
AB  - Current yeast interactome network maps contain several hundred molecular
      complexes with limited and somewhat controversial representation of direct binary
      interactions. We carried out a comparative quality assessment of current yeast
      interactome data sets, demonstrating that high-throughput yeast two-hybrid (Y2H)
      screening provides high-quality binary interaction information. Because a large
      fraction of the yeast binary interactome remains to be mapped, we developed an
      empirically controlled mapping framework to produce a "second-generation" high
      quality, high-throughput Y2H data set covering approximately 20% of all yeast
      binary interactions. Both Y2H and affinity purification followed by mass
      spectrometry (AP/MS) data are of equally high quality but of a fundamentally
      different and complementary nature, resulting in networks with different
      topological and biological properties. Compared to co-complex interactome models,
      this binary map is enriched for transient signaling interactions and intercomplex
      connections with a highly significant clustering between essential proteins.
      Rather than correlating with essentiality, protein connectivity correlates with
      genetic pleiotropy.

PMID- 18719257
TI  - Genomics. 'Simple' animal's genome proves unexpectedly complex.

PMID- 18719258
TI  - Endangered species. New regulation would lessen influence of fish and wildlife
      experts.

PMID- 18719259
TI  - U.S. higher education. Departments scramble to find math education faculty.

PMID- 18719260
TI  - Climate science. Turbulent times for climate model.

PMID- 18719261
TI  - Cultural heritage. Shielding a Buddhist shrine from the howling desert sands.

PMID- 18719263
TI  - An editor's checklist.

PMID- 18719262
TI  - Nanotechnology. Can high-speed tests sort out which nanomaterials are safe?

PMID- 18719264
TI  - High-profile journals not worth the trouble.

PMID- 18719265
TI  - Taking responsibility for scientific discourse.

PMID- 18719266
TI  - Comment on "Protein sequences from mastodon and Tyrannosaurus rex revealed by
      mass spectrometry".
AB  - Asara et al. (Reports, 13 April 2007, p. 280) reported sequencing of
      Tyrannosaurus rex proteins and used them to establish the evolutionary
      relationships between birds and dinosaurs. We argue that the reported T. rex
      peptides may represent statistical artifacts and call for complete data release
      to enable experimental and computational verification of their findings.

PMID- 18719267
TI  - The carrageenan diet: not recommended.

PMID- 18719268
TI  - Ecology. Toward a global biodiversity observing system.

PMID- 18719269
TI  - Psychology. The unseen mind.

PMID- 18719270
TI  - Astronomy. Stars in the making.

PMID- 18719271
TI  - Developmental biology. How now, brown fat?

PMID- 18719272
TI  - Chemistry. Soluble allotropes of main-group elements.

PMID- 18719273
TI  - Ecology. A matter of timing.

PMID- 18719274
TI  - Plant science. Using tobacco to treat cancer.

PMID- 18719275
TI  - The geological evolution of the Tibetan Plateau.
AB  - The geological evolution of the Tibetan plateau is best viewed in a context
      broader than the India-Eurasia collision zone. After collision about 50 million
      years ago, crust was shortened in western and central Tibet, while large
      fragments of lithosphere moved from the collision zone toward areas of trench
      rollback in the western Pacific and Indonesia. Cessation of rapid Pacific trench
      migration ( approximately 15 to 20 million years ago) coincided with a slowing of
      fragment extrusion beyond the plateau and probably contributed to the onset of
      rapid surface uplift and crustal thickening in eastern Tibet. The latter appear
      to result from rapid eastward flow of the deep crust, probably within crustal
      channels imaged seismically beneath eastern Tibet. These events mark a transition
      to the modern structural system that currently accommodates deformation within
      Tibet.

PMID- 18719276
TI  - Star formation around supermassive black holes.
AB  - The presence of young massive stars orbiting on eccentric rings within a few
      tenths of a parsec of the supermassive black hole in the galactic center is
      challenging for theories of star formation. The high tidal shear from the black
      hole should tear apart the molecular clouds that form stars elsewhere in the
      Galaxy, and transport of stars to the galactic center also appears unlikely
      during their lifetimes. We conducted numerical simulations of the infall of a
      giant molecular cloud that interacts with the black hole. The transfer of energy
      during closest approach allows part of the cloud to become bound to the black
      hole, forming an eccentric disk that quickly fragments to form stars.
      Compressional heating due to the black hole raises the temperature of the gas up
      to several hundred to several thousand kelvin, ensuring that the fragmentation
      produces relatively high stellar masses. These stars retain the eccentricity of
      the disk and, for a sufficiently massive initial cloud, produce an extremely top
      heavy distribution of stellar masses. This potentially repetitive process may
      explain the presence of multiple eccentric rings of young stars in the presence
      of a supermassive black hole.

PMID- 18719277
TI  - Quantum gas of deeply bound ground state molecules.
AB  - Molecular cooling techniques face the hurdle of dissipating translational as well
      as internal energy in the presence of a rich electronic, vibrational, and
      rotational energy spectrum. In our experiment, we create a translationally
      ultracold, dense quantum gas of molecules bound by more than 1000 wave numbers in
      the electronic ground state. Specifically, we stimulate with 80% efficiency, a
      two-photon transfer of molecules associated on a Feshbach resonance from a Bose
      Einstein condensate of cesium atoms. In the process, the initial loose, long
      range electrostatic bond of the Feshbach molecule is coherently transformed into
      a tight chemical bond. We demonstrate coherence of the transfer in a Ramsey-type
      experiment and show that the molecular sample is not heated during the transfer.
      Our results show that the preparation of a quantum gas of molecules in specific
      rovibrational states is possible and that the creation of a Bose-Einstein
      condensate of molecules in their rovibronic ground state is within reach.

PMID- 18719278
TI  - Observation of atomic diffusion at twin-modified grain boundaries in copper.
AB  - Grain boundaries affect the migration of atoms and electrons in polycrystalline
      solids, thus influencing many of the mechanical and electrical properties. By
      introducing nanometer-scale twin defects into copper grains, we show that we can
      change the grain-boundary structure and atomic-diffusion behavior along the
      boundary. Using in situ ultrahigh-vacuum and high-resolution transmission
      electron microscopy, we observed electromigration-induced atomic diffusion in the
      twin-modified grain boundaries. The triple point where a twin boundary meets a
      grain boundary was found to slow down grain-boundary and surface electromigration
      by one order of magnitude. We propose that this occurs because of the incubation
      time of nucleation of a new step at the triple points. The long incubation time
      slows down the overall rate of atomic transport.

PMID- 18719279
TI  - A stable silicon(0) compound with a Si=Si double bond.
AB  - Dative, or nonoxidative, ligand coordination is common in transition metal
      complexes; however, this bonding motif is rare in compounds of main group
      elements in the formal oxidation state of zero. Here, we report that the
      potassium graphite reduction of the neutral hypervalent silicon-carbene complex
      L:SiCl4 {where L: is:C[N(2,6-Pri2-C6H3)CH]2 and Pri is isopropyl} produces
      L:(Cl)Si-Si(Cl):L, a carbene-stabilized bis-silylene, and L:Si=Si:L, a carbene
      stabilized diatomic silicon molecule with the Si atoms in the formal oxidation
      state of zero. The Si-Si bond distance of 2.2294 +/- 0.0011 (standard deviation)
      angstroms in L:Si=Si:L is consistent with a Si=Si double bond. Complementary
      computational studies confirm the nature of the bonding in L:(Cl)Si-Si(Cl):L and
      L:Si=Si:L.

PMID- 18719280
TI  - The global atmospheric circulation on moist isentropes.
AB  - The global atmospheric circulation transports energy from the equatorial regions
      to higher latitudes through a poleward flow of high-energy and -entropy parcels
      and an equatorward flow of air with lower energy and entropy content. Because of
      its turbulent nature, this circulation can only be described in some averaged
      sense. Here, we show that the total mass transport by the circulation is twice as
      large when averaged on moist isentropes than when averaged on dry isentropes. The
      additional mass transport on moist isentropes corresponds to a poleward flow of
      warm moist air near Earth's surface that rises into the upper troposphere within
      mid-latitudes and accounts for up to half of the air in the upper troposphere in
      polar regions.

PMID- 18719281
TI  - Targeting QseC signaling and virulence for antibiotic development.
AB  - Many bacterial pathogens rely on a conserved membrane histidine sensor kinase,
      QseC, to respond to host adrenergic signaling molecules and bacterial signals in
      order to promote the expression of virulence factors. Using a high-throughput
      screen, we identified a small molecule, LED209, that inhibits the binding of
      signals to QseC, preventing its autophosphorylation and consequently inhibiting
      QseC-mediated activation of virulence gene expression. LED209 is not toxic and
      does not inhibit pathogen growth; however, this compound markedly inhibits the
      virulence of several pathogens in vitro and in vivo in animals. Inhibition of
      signaling offers a strategy for the development of broad-spectrum antimicrobial
      drugs.

PMID- 18719282
TI  - Variability and robustness in T cell activation from regulated heterogeneity in
      protein levels.
AB  - In T cells, the stochasticity of protein expression could contribute to the
      useful diversification of biological functions within a clonal population or
      interfere with accurate antigen discrimination. Combining computer modeling and
      single-cell measurements, we examined how endogenous variation in the expression
      levels of signaling proteins might affect antigen responsiveness during T cell
      activation. We found that the CD8 co-receptor fine-tunes activation thresholds,
      whereas the soluble hematopoietic phosphatase 1 (SHP-1) digitally regulates cell
      responsiveness. Stochastic variation in the expression of these proteins
      generates substantial diversity of activation within a clonal population of T
      cells, but co-regulation of CD8 and SHP-1 levels ultimately limits this very
      diversity. These findings reveal how eukaryotic cells can draw on regulated
      variation in gene expression to achieve phenotypic variability in a controlled
      manner.

PMID- 18719283
TI  - Adenovirus small e1a alters global patterns of histone modification.
AB  - Adenovirus small early region 1a (e1a) protein drives cells into S phase by
      binding RB family proteins and the closely related histone acetyl transferases
      p300 and CBP. The interaction with RB proteins displaces them from DNA-bound E2F
      transcription factors, reversing their repression of cell cycle genes. However,
      it has been unclear how the e1a interaction with p300 and CBP promotes passage
      through the cell cycle. We show that this interaction causes a threefold
      reduction in total cellular histone H3 lysine 18 acetylation (H3K18ac). CBP and
      p300 are required for acetylation at this site because their knockdown causes
      specific hypoacetylation at H3K18. SV40 T antigen also induces H3K18
      hypoacetylation. Because global hypoacetylation at this site is observed in
      prostate carcinomas with poor prognosis, this suggests that processes resulting
      in global H3K18 hypoacetylation may be linked to oncogenic transformation.

PMID- 18719284
TI  - Epigenetic reprogramming by adenovirus e1a.
AB  - Adenovirus e1a induces quiescent human cells to replicate. We found that e1a
      causes global relocalization of the RB (retinoblastoma) proteins (RB, p130, and
      p107) and p300/CBP histone acetyltransferases on promoters, the effect of which
      is to restrict the acetylation of histone 3 lysine-18 (H3K18ac) to a limited set
      of genes, thereby stimulating cell cycling and inhibiting antiviral responses and
      cellular differentiation. Soon after expression, e1a binds transiently to
      promoters of cell cycle and growth genes, causing enrichment of p300/CBP, PCAF
      (p300/CBP-associated factor), and H3K18ac; depletion of RB proteins; and
      transcriptional activation. e1a also associates transiently with promoters of
      antiviral genes, causing enrichment for RB, p130, and H4K16ac; increased
      nucleosome density; and transcriptional repression. At later times, e1a and p107
      bind mainly to promoters of development and differentiation genes, repressing
      transcription. The temporal order of e1a binding requires its interactions with
      p300/CBP and RB proteins. Our data uncover a defined epigenetic reprogramming
      leading to cellular transformation.

PMID- 18719285
TI  - Heterochromatin integrity affects chromosome reorganization after centromere
      dysfunction.
AB  - The centromere is essential for the inheritance of genetic information on
      eukaryotic chromosomes. Epigenetic regulation of centromere identity has been
      implicated in genome stability, karyotype evolution, and speciation. However,
      little is known regarding the manner in which centromere dysfunction affects the
      chromosomal architectures. Here we show that in the fission yeast
      Schizosaccharomyces pombe, the conditional deletion of the centromere produces
      survivors that carry either a neocentromere-acquired chromosome at the
      subtelomeric region or an acentric chromosome rescued by intertelomere fusion
      with either of the remaining chromosomes. The ratio of neocentromere formation to
      telomere fusion is considerably decreased by the inactivation of genes involved
      in RNA interference-dependent heterochromatin formation. By affecting the modes
      of chromosomal reorganization, the genomic distribution of heterochromatin may
      influence the fate of karyotype evolution.

PMID- 18719286
TI  - Grueneberg ganglion cells mediate alarm pheromone detection in mice.
AB  - Alarm pheromones (APs) are widely used throughout the plant and animal kingdoms.
      Species such as fish, insects, and mammals signal danger to conspecifics by
      releasing volatile alarm molecules. Thus far, neither the chemicals, their bodily
      source, nor the sensory system involved in their detection have been isolated or
      identified in mammals. We found that APs are recognized by the Grueneberg
      ganglion (GG), a recently discovered olfactory subsystem. We showed with electron
      microscopy that GG neurons bear primary cilia, with cell bodies ensheathed by
      glial cells. APs evoked calcium responses in GG neurons in vitro and induced
      freezing behavior in vivo, which completely disappeared when the GG degenerated
      after axotomy. We conclude that mice detect APs through the activation of
      olfactory GG neurons.

PMID- 18719287
TI  - Control of the reversibility of cellular quiescence by the transcriptional
      repressor HES1.
AB  - The mechanisms by which quiescent cells, including adult stem cells, preserve
      their ability to resume proliferation after weeks or even years of cell cycle
      arrest are not known. We report that reversibility is not a passive property of
      nondividing cells, because enforced cell cycle arrest for a period as brief as 4
      days initiates spontaneous, premature, and irreversible senescence. Increased
      expression of the gene encoding the basic helix-loop-helix protein HES1 was
      required for quiescence to be reversible, because HES1 prevented both premature
      senescence and inappropriate differentiation in quiescent fibroblasts. In some
      human tumors, the HES1 pathway was activated, which allowed these cells to evade
      differentiation and irreversible cell cycle arrest. We conclude that HES1
      safeguards against irreversible cell cycle exit both during normal cellular
      quiescence and pathologically in the setting of tumorigenesis.

PMID- 18719288
TI  - Automatic mental associations predict future choices of undecided decision
      makers.
AB  - Common wisdom holds that choice decisions are based on conscious deliberations of
      the available information about choice options. On the basis of recent insights
      about unconscious influences on information processing, we tested whether
      automatic mental associations of undecided individuals bias future choices in a
      manner such that these choices reflect the evaluations implied by earlier
      automatic associations. With the use of a computer-based, speeded categorization
      task to assess automatic mental associations (i.e., associations that are
      activated unintentionally, difficult to control, and not necessarily endorsed at
      a conscious level) and self-report measures to assess consciously endorsed
      beliefs and choice preferences, automatic associations of undecided participants
      predicted changes in consciously reported beliefs and future choices over a
      period of 1 week. Conversely, for decided participants, consciously reported
      beliefs predicted changes in automatic associations and future choices over the
      same period. These results indicate that decision-makers sometimes have already
      made up their mind at an unconscious level, even when they consciously indicate
      that they are still undecided.

PMID- 18719290
TI  - Involvement of the neurokinin-2 receptor in airway smooth muscle stretch
      activated contractions assessed in perfused intact bovine bronchial segments.
AB  - The airway response to deep inspirations (DIs) in asthmatics has been shown to be
      ineffective in producing bronchodilation and can even cause bronchoconstriction.
      However, the manner by which a DI is able to cause bronchoconstriction remains
      ambiguous. We sought to investigate the pathway involved in this stretch
      activated contraction and whether this contraction is intrinsic to airway smooth
      muscle (ASM). In brief, intact bovine bronchial segments were dissected, and side
      branches were ligated and then mounted horizontally in an organ bath.
      Intraluminal pressure was measured under isovolumic conditions. Instantaneously
      opening and then closing the tap on a column of fluid 5 to 30 cm high evoked a
      sudden increase in intraluminal pressure (equivalent to the height of the column
      of fluid) followed by a stress relaxation response of the ASM. When tissues were
      stimulated with carbachol (10(-8) M) or serotonin (10(-7) M) for 10 min, and the
      consequent agonist-evoked pressure response was dissipated manually, the response
      to the same transmural stretch was accompanied by a slowly developing and
      prolonged increase in intraluminal pressure. This stretch-activated response was
      significantly diminished by the stretch-activated cation channel blocker
      gadolinium (10(-3) M), the L-type Ca2+ channel blockers nifedipine (2 x 10(-6)
      M), diltiazem (10(-5) M), and verapamil (10(-5) M), the sensory neurotoxin
      capsaicin (10(-5) M), and the neurokinin (NK)(2) receptor antagonists MEN 10376
      ([Tyr(I),d-Trp(6,8,9),Lys(10)]-NKA(4-10)) (10(-5) M) and SR48968 (N-[(2S)-4-(4
      acetamido-4-phenylpiperidin-1-yl)-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide)
      (3 x 10(-6) M). These results show the ability of isolated airways to exhibit
      stretch-activated contractions and suggest a role for stretch-activated cation
      channels, sensory afferent neurons, the neurotransmitter NKA, and L-type Ca(2+)
      channels in these isolated airway responses.

PMID- 18719291
TI  - Increasing systemic exposure of methotrexate by active efflux mediated by
      multidrug resistance-associated protein 3 (mrp3/abcc3).
AB  - The aim of this study was to investigate the functional importance of multidrug
      resistance-associated protein (Mrp)3/Abcc3 and Mrp4/Abcc4 in the pharmacokinetics
      of methotrexate. Compared with the corresponding wild-type mice, the plasma
      concentrations of methotrexate given orally were similar in Abcc4(-/-) mice and
      were significantly lower in Abcc3(-/-) mice. Pharmacokinetic parameters related
      to hepatobiliary transport were determined under steady-state conditions in wild
      type and Abcc3(-/-) mice that were given a constant intravenous infusion of
      methotrexate. The biliary clearance, based on the plasma concentration, was 1.6
      fold greater in Abcc3(-/-) mice than in wild-type mice (23 and 15 ml/min/kg,
      respectively, P < 0.05). Because the basolateral uptake and canalicular efflux
      clearances of methotrexate were similar in wild-type and Abcc3(-/-) mice, this
      result suggests that the basolateral efflux clearance of methotrexate is
      decreased in the liver of Abcc3(-/-) mice. Furthermore, a lower fraction of
      absorption of methotrexate (F(a) F(g)) was suggested in Abcc3(-/-) mice (0.49 and
      0.29 in wild-type and Abcc3(-/-) mice, respectively). The mucosal-to-serosal
      transport rate of methotrexate, determined in vitro using everted sacs, was
      highest in the duodenum and was significantly decreased in Abcc3(-/-) mice
      compared with wild-type mice. This is ascribed to the reduced intrinsic efflux
      clearance of methotrexate across the serosal membrane (22 and 5.3 mul/min/sac in
      wild-type and Abcc3(-/-) mice, respectively, P < 0.05). These results suggest
      that Mrp3 mediates basolateral efflux of methotrexate in the liver and duodenum,
      thereby serving to increase systemic exposure, whereas Mrp4 is likely to play
      only a limited role in the systemic methotrexate exposure.

PMID- 18719292
TI  - Perinatal exposure to brominated flame retardants and polychlorinated biphenyls
      in Japan.
AB  - Brominated flame retardants (BFRs) are used to prevent combustion in consumer
      products. Examples of BFRs are polybrominated diphenyl ethers (PBDEs),
      tetrabromobisphenol A (TBBPA), and tribromophenol (TBP). These compounds are
      reported to have adverse effects on human health and endocrine disrupting
      effects. The purpose of this study was to identify the Japanese perinatal
      exposure to PBDEs, hydroxylated PBDE metabolites (OH-PBDEs), TBBPA, and TBP
      compared with polychlorinated biphenyls (PCBs) and hydroxylated PCB metabolites
      (OH-PCBs). We investigated the concentrations of these compounds in maternal
      blood, maternal milk, cord blood, and umbilical cords from 16 Japanese mother
      infant pairs by HRGC/HRMS. PBDEs were detected in all samples of maternal blood
      (mean+/-SD; median=25+/-23 pg/g; 18 pg/g wet weight), maternal milk (140+/-220
      pg/g; 59 pg/g wet weight), cord blood (4.8+/-6.5 pg/g; 1.6 pg/g wet weight), and
      umbilical cords (3.1+/-3.1 pg/g; 2.1 pg/g wet weight). The mothers were divided
      into two groups, a high-concentration group and a low-concentration group. The
      percentage of BDE-47 showed the greatest difference between the two groups. 6-OH
      BDE-47, TBBPA, and TBP were detected in all umbilical cord samples (mean+/-SD;
      median=8.4+/-8.1 pg/g; 8.0 pg/g, 16+/-5.5 pg/g; 15 pg/g, and 33+/-8.2 pg/g; 32
      pg/g wet weight respectively), but not in all maternal blood or cord blood
      samples. These results indicate that OH-PBDEs, TBBPA, and TBP, in addition to
      PBDEs, PCBs, and OH-PCBs, pass through the blood-placenta barrier and are
      retained in the umbilical cord.

PMID- 18719293
TI  - Endocrinological analysis of 122 Japanese childhood cancer survivors in a single
      hospital.
AB  - With recent improvements in the diagnosis and treatment of cancer, the number of
      childhood cancer survivors (CCSs) has been increasing in Japan. The importance of
      quality of life during the lifetime of CCSs has now been recognized, and the late
      effects of cancer treatments are essential and important issues. In this study we
      analyzed the endocrinological abnormalities of CCSs by retrospectively evaluating
      122 outpatients (62 males and 60 females) who had been referred from pediatric
      oncologists to our follow-up clinic among 151 CCSs attending our hospital more
      than two years after their cancer treatment. Follow-up duration varied from 2 to
      30 (median 8.0) years. Their average age was 17.3 (range 4-36, median 17.0)
      years, and 38 patients (31.1%) reached adulthood. Endocrinological abnormalities
      were found in 82 (67%) of 122 survivors. Gonadal dysfunction was observed in 60
      patients (49%). Thirty-nine patients (32%) were short or grew at a slower rate.
      Twenty-six patients (21%) showed thyroid dysfunction. Other abnormalities were as
      follows: obesity in 20 patients (16%), leanness in 10 (8%), central diabetes
      insipidus in 11 (9%) and adrenocortical dysfunction in 9 (7%). Low bone mineral
      density was observed in 41 (42%) of 98 patients evaluated. These endocrinological
      abnormalities were caused by the combined effects of cancer itself and various
      treatments (chemotherapy, radiation therapy, surgery, and hematopoietic stem cell
      transplantation). Lifetime medical surveillance and continuous follow-up are
      necessary for CCSs, because treatment-related complications may occur during
      childhood and many years after the therapy as well. Endocrinologists should
      participate in long-term follow-up of these survivors in collaboration with
      pediatric oncologists.

PMID- 18719294
TI  - Hypospadias in a male patient with 21-hydroxylase deficiency.
AB  - A 17-day-old Japanese boy was transferred to the hospital because of vomiting and
      impaired consciousness. His external genitalia was pigmented associated with
      small penis and penoscrotal hypospadias. He was diagnosed as suffering from
      adrenal deficiency according to severe electrolyte abnormality, moderate
      hypoglycemia, metabolic acidosis and extremely elevated 17-OHP and testosterone
      levels. He turned out to be a compound heterozygote of CYP21A2 mutations by
      genetic analysis. Through endocrinological evaluation, he seemed to have normal
      hypophyseal function, intact testosterone production and appropriate 5-alpha
      reductase-2 activity. Partial androgen insensitivity could not be ruled out by
      slight decrease of SHBG in hCG loading test, although mutation was not detected
      on androgen receptor gene. This is a rare case of a male patient with 21
      hydroxylase deficiency accompanied by hypospadias. As the cause of hypospadias in
      this case has yet to be elucidated, further investigation and careful follow-up
      are required.

PMID- 18719295
TI  - [Pilot study of domain-specific terminology adaptation for morphological
      analysis: research on unknown terms in national examination documents of
      radiological technologists].
AB  - Although large medical texts are stored in electronic format, they are seldom
      reused because of the difficulty of processing narrative texts by computer.
      Morphological analysis is a key technology for extracting medical terms correctly
      and automatically. This process parses a sentence into its smallest unit, the
      morpheme. Phrases consisting of two or more technical terms, however, cause
      morphological analysis software to fail in parsing the sentence and output
      unprocessed terms as "unknown words." The purpose of this study was to reduce the
      number of unknown words in medical narrative text processing. The results of
      parsing the text with additional dictionaries were compared with the analysis of
      the number of unknown words in the national examination for radiologists. The
      ratio of unknown words was reduced 1.0% to 0.36% by adding terminologies of
      radiological technology, MeSH, and ICD-10 labels. The terminology of radiological
      technology was the most effective resource, being reduced by 0.62%. This result
      clearly showed the necessity of additional dictionary selection and trends in
      unknown words. The potential for this investigation is to make available a large
      body of clinical information that would otherwise be inaccessible for
      applications other than manual health care review by personnel.

PMID- 18719296
TI  - [Verification of irradiation conditions of X-rays that influence implantable
      cardiac pacemakers].
AB  - Originally, it was thought that X-rays did not influence implantable cardiac
      pacemakers. In general, radiological technologists did not take proper care of
      these devises at the time of X-Ray examinations. However, 11 cases in which
      pacemakers malfunctioned (for example partial electrical reset) during CT
      examinations have been reported in recent years. At the time, we tended to
      attribute such problems to the peculiarities of multi-detector CT (MDCT).
      However, on logical grounds this explanation seemed weak. To better explain the
      problem, we attempted various tests in which pacemakers were exposed to CT and X
      ray photography equipment. We analyzed some ECG results to clarify the matter and
      took measurements to examine these problems.

PMID- 18719297
TI  - [Effect of diagnostic X-rays on implantable cardiac pacemakers and implantable
      cardioverter defibrillators, and its management].
AB  - The effects of diagnostic X-rays on implantable cardiac pacemakers and
      implantable cardioverter defibrillators (ICDs) were investigated. A total of 33
      pacemakers from six manufacturers and nine ICDs from four manufacturers were
      irradiated using several X-ray units (plain X-ray diagnostic unit, under-table
      system fluoroscopy unit, over-table system fluoroscopy unit, biplane cardiac
      digital angiography unit, DSA unit and cone-beam CT unit). No systematic reset
      phenomena were observed in any pacemakers and ICDs under the X-ray irradiation.
      Nevertheless, over-sensing associated with the lack of a few pulses was observed
      in three of 33 pacemakers under radiation exposure. It has been proven that
      diagnostic X-rays might affect pacemaker function. Since the duration of the over
      sensing under the radiation was very short and included transient episodes, this
      sensing failure, therefore, induced by radiation exposure would not affect the
      health of pacemaker recipients. ICDs were not affected by radiation exposure at a
      clinical dose. It is recommended that caution be exercised in direct irradiation
      to the pacemaker. Using a copper sheet of 2.0 mm thickness or more prevented over
      sensing of pacemakers in the present study, especially when serial X-ray
      exposures were used with an over-table fluoroscopy system or cone-beam CT unit.

PMID- 18719298
TI  - [Quantitative assessment of wall motion in gated SPECT using the centerline
      method].
AB  - Evaluation of myocardial wall motion is an important assessment of heart
      function. Specific analysis programs in nuclear medicine, such as QGS
      (quantitative gated SPECT) analysis and p-FAST (perfusion-function assessment for
      myocardial SPECT), have been used to assess wall motion, but they have not
      evaluated it through a comparison of normal data. The centerline method, using
      left ventriculograms (LVG), evaluates regional wall motion quantitatively through
      a comparison of normal data and patient data, and abnormality of wall motion is
      expressed in units of standard deviation (SD) s from the mean motion in a
      reference population. However, angiography is an invasive inspection, wall motion
      analysis is usually in one direction, and the conventional centerline method is
      not a three-dimensional analysis. The purpose of this study was to apply the
      centerline method to nuclear medicine and examine the wall motion of subjects
      through a comparison of normal wall motion non-invasively and in a three
      dimensional way. We arranged the analysis program using C language and inspected
      it using a dynamic cardiac phantom and computed tomography (CT) scanner. We made
      a polar map that indicated the mean and SD of normal wall motion. Our proposed
      method was able to assess the wall motion of subjects quantitatively through a
      comparison of normal wall motion in nuclear medicine.

PMID- 18719299
TI  - [Evaluation of the OS-EM parameter with automatic quantitative analysis for
      cerebral blood flow of the ECD tool].
AB  - The parameters of reconstruction iteration and subset of the ordered subset
      expectation maximization (OS-EM) method have a great impact on image quality. In
      a cerebral blood flow (CBF) examination, it is critical to produce consistent
      results when analyzing clinical data. We evaluated the number of iterations and
      subset of the OS-EM method to stabilize image quality using a normal case and an
      infarction case. In the maximum likelihood expectation maximization (ML-EM)
      method, it was confirmed that the convergence of an infarction case was somewhat
      delayed compared with a normal case. With the OS-EM method, we have obtained the
      same results. Based on the rCBF values, we postulate that the iteration value is
      more than 8 and the subset value is less than 10. Furthermore, multiplying the
      iteration by a subset value ranging from 50 to 60 helps in stabilizing the
      quality of CBF imaging.

PMID- 18719300
TI  - [Radiographic examinations for oral and maxillofacial lesions-interpretation of
      panoramic radiography & plain radiography].

PMID- 18719301
TI  - [Nuclear medicine in endocrinology and respiratory diseases].

PMID- 18719302
TI  - [Fundamental technology for computer-aided diagnosis. 3. Image processing in
      spatial frequency domain].

PMID- 18719303
TI  - [Useful tips of diffusion-weighted imaging-optimization of scan parameters].

PMID- 18719304
TI  - [Subtraction image for dynamic liver MRI using free breath-hold at functional
      residual capacity: a clinical trial].
AB  - PURPOSE: Dynamic liver MRI images have been obtained under expiration breath
      holding (BH). However, problems with obtaining reproducible liver positions often
      observed. This study investigated ways to improve the reproducibility of liver
      position on dynamic liver MRI. MATERIALS AND METHODS: After giving informed
      consent, 60 patients (32 males and 28 females, ages 33-85, median age 69) were
      examined by liver dynamic MRI under two types of BH. The BH phases were voluntary
      expiration (VE) phase without any explanations and functional residual capacity
      (FRC) phase after careful explanation was provided. Plain images, arterial phase
      images, portal phase images and parenchymal phase images were obtained. For
      statistical evaluation of reproducibility, the area of the 2nd or 3rd images from
      top of the liver was measured in each phase using a threshold value of half
      maximum. Misregistration areas were calculated by finding the remainder of the
      liver area in the plain-arterial (Pl-A) phase, arterial-portal (A-Po) phase,
      plain-parenchymal (Pl-Pa) phase. Contingency table analysis was done due to the
      misregistration was occurred or not. RESULTS: Misregistration of liver image on
      the VE and the FRC of three phase types were statistical significant on the Pl-A
      (p < 0.01), on the A-Po (p < 0.01) and on the Pl-Pa (p < 0.05), respectively.
      CONCLUSION: The FRC phase following careful explanation of the BH provided
      significantly improved reproducibility of liver position on dynamic liver MRI.
      Therefore, precise subtraction images could be obtained for routine clinical
      examinations without slice matching.

PMID- 18719305
TI  - [The utility of coronary magnetic resonance angiography in children under six
      years of age with Kawasaki disease].
AB  - BACKGROUND: To follow up coronary arterial lesions due to Kawasaki disease (KD)
      using noninvasive magnetic resonance coronary angiography (MRCA), we studied a
      method to improve the quality of images in young children. METHOD: Non-contrast
      enhanced, free-breathing MRCA with the vector ECG gating real-time navigator-echo
      3D steady-state free precession (SSFP) technique was performed using a 1.5-T
      whole-body MR imaging system (Philips) in 68 children with KD aged 4 months to
      less than 6 years. A flex medium coil was used. Data were acquired with a 180 to
      200 mm field of view (FOV) and were reconstructed with a 512 x 360 matrix.
      Patients were sedated during the examination. Many parameters were optimized for
      each patient; i.e., FOV, acquisition delay, turbo-field echo-factor, navigator
      window and resolution, which resulted in the acquisition of high-resolution and
      high-signal images of the coronary arteries. RESULTS: These conditions remarkably
      improved not only the quality of the images, but also the detection rate of
      coronary arterial segments (American Heart Association) in the children. The
      rates were as follows; Segments 1 (97%), 2 (97%), 3 (87%), 4 (66%), 5 (97%), 6
      (96%), 7 (83%), 8 (56%), 9 (53%), 10 (21%), 11 (96%), 12 (29%), 13 (93%), 14
      (54%), and 15 (65%). CONCLUSION: MRCA is a useful method for evaluation coronary
      aneurysms from the early stages of KD, even in infants and small children.

PMID- 18719306
TI  - [Investigation of the accurate measurement of the basic imaging properties for
      the digital radiographic system based on flat panel detector].
AB  - PURPOSE/AIM OF THE EXHIBIT: The purpose of this exhibit is: 1. To explain
      "resampling", an image data processing, performed by the digital radiographic
      system based on flat panel detector (FPD). 2. To show the influence of
      "resampling" on the basic imaging properties. 3. To present accurate measurement
      methods of the basic imaging properties of the FPD system. CONTENT ORGANIZATION:
      1. The relationship between the matrix sizes of the output image and the image
      data acquired on FPD that automatically changes depending on a selected image
      size (FOV). 2. The explanation of the image data processing of "resampling". 3.
      The evaluation results of the basic imaging properties of the FPD system using
      two types of DICOM image to which "resampling" was performed: characteristic
      curves, presampled MTFs, noise power spectra, detective quantum efficiencies.
      CONCLUSION/SUMMARY: The major points of the exhibit are as follows: 1. The
      influence of "resampling" should not be disregarded in the evaluation of the
      basic imaging properties of the flat panel detector system. 2. It is necessary
      for the basic imaging properties to be measured by using DICOM image to which no
      "resampling" is performed.

PMID- 18719307
TI  - [False-negative cases of axillary ultrasonography: how much size?].
AB  - PURPOSE/AIM: 1. To review the sonographic criteria of axillary lymph node status
      in breast cancer patients. 2. To understand imaging pathologic correlations that
      the false-negative cases of axillary ultrasonography. CONTENT ORGANIZATION: The
      sonographic criteria, the accuracy of sonographic axillary ultrasonography,
      imaging pathologic correlations in false-negative cases, measurement of largest
      malignant focus size in lymph node, classification of ratio of malignant focus
      size, ratio of micro metastasis. SUMMARY: 1. Recently, lymph node evaluation that
      using serial section and immunohistochemical stains makes it difficult to detect
      imaging modalities. 2. Ultrasonography is limited how to detect the example of
      sentinel lymph node biopsy non-indications.

PMID- 18719308
TI  - [Improvement of detection of early CT signs in hyperacute stroke using a novel
      noise reduction filter].
AB  - PURPOSE: In the diagnosis of hyperacute stroke, an early CT sign such as the loss
      of gray-white matter interface may be difficult to detect within the first hours
      of the onset of symptoms because of the presence of quantum noise on CT images.
      We present a method for improving the detection of early CT sign, and to evaluate
      whether our method can help radiologists detect the early CT signs at emergency
      CT scan. METHODS AND MATERIALS: Our method provides an adaptive partial median
      filter (APMF), which can reduce local noise without blurring of anatomical
      structure using variable filter shape and size according to the pixel value
      distribution of object around a center pixel. The APMF can enhance the loss of
      gray-white matter interface due to hyperacute stroke. Twenty-six patients with
      early CT signs at the lentiform nucleus and/or the cortical ribbon and 49 control
      subjects were included in an observer study. The CT images of 26 patients with
      acute (<5 hours) middle cerebral artery territory infarction were proved with
      follow-up CT. The APMF was applied to all the CT images. Four radiologists,
      without and with applying the APMF, indicated their confidence level regarding
      the presence (or absence) of the early CT signs on each CT images. Receiver
      operating characteristic (ROC) curves were calculated to evaluate the observers'
      performance. RESULTS: A 78% noise reduction with the APMF was obtained from
      simulation. The average area under the ROC curve (Az) was improved from 0.868 to
      0.924 for all radiologists by applying the APMF to the original images. The
      difference in Az values with and without the APMF was statistically significant
      with a P value of .002 for all radiologists. CONCLUSION: Our proposed APMF can
      improve the visibility of gray-white matter interface. As a result, the APMF can
      help radiologists detect the early CT signs at emergency CT scan.

PMID- 18719309
TI  - [Investigation of the local heating caused by a closed conducting loop at
      clinical MR imaging: Phantom study].
AB  - PURPOSE: Several reports have suggested that unusual thermal injuries in magnetic
      resonance (MR) imaging have occurred due to a closed conducting loop formed
      accidentally in a part of the patient's body. In this study, we investigated the
      relationship between the increases in temperature and several parameter settings
      for MR imaging by use of a human body-equivalent phantom. METHOD AND MATERIALS: A
      standard clinical 1.5T MR system (SIGNA HORIZON; GE) and a pelvic phased-array
      coil were used. The human body-equivalent phantom (agar, 0.9% saline, antiseptic)
      simulated a part of the pelvis and both femurs in a patient. A closed conducting
      loop could be reproduced when two ends of femurs contacted each other at a point,
      so that we could measure the temperature changes without and with a closed
      conducting loop. The temperature of the phantom was measured at the contact point
      of a closed conducting loop and the center of phantom by use of an optical fiber
      thermometer which was immune to the influences of radiofrequency (RF) and
      magnetic and electronic fields. We tested two imaging sequences of spin echo (SE)
      and fast spin echo (FSE) with 60 minutes of scanning time. In addition to the
      standard imaging sequences we measured temperature changes without the RF
      irradiation or gradient magnetic fields. The average temperature changes were
      recorded from five measurements which were repeated at intervals of more than one
      day. RESULTS: When the closed conducting loop was reproduced, the temperatures at
      the contact point significantly increased (p<0.001) compared with the
      temperatures at the center of phantom. The temperature changes at 60 minutes of
      scanning time were 7.0 and 8.1 degrees C by use of the SE and FSE, respectively.
      There were no significant temperature changes when the imaging was performed
      without the RF irradiation. CONCLUSION: Our result obtained by use of a human
      body-equivalent phantom demonstrated that local heating, which can lead to
      thermal injuries accidentally, could occur when a closed conducting loop was
      formed in part of the patient body. CLINICAL RELEVANCE/APPLICATION: Radiologists
      should be more careful about local heating which can occur in patients during
      clinical MR imaging by a closed conducting loop.

PMID- 18719310
TI  - [The more we spend on discussions, the more research can be improved].

PMID- 18719311
TI  - [Particular requirements for the safety of mammographic X-ray equipment and
      mammographic stereotactic devices JIS Z 4751-2-45: 2006(IEC60601-2-45: 2001)].

PMID- 18719312
TI  - [Investigation into the actual conditions about electromagnetic compatibility of
      medical electrical equipment and information technology equipment in hospital].

PMID- 18719313
TI  - [ISO/TC215 WG4 Brisbane Meeting Report].

PMID- 18719314
TI  - Immunosuppression induced by a conditioned stimulus associated with cocaine self
      administration.
AB  - Cocaine addiction is known to impair immune system function, but the effects of
      repeated treatment with cocaine in a self-administration model, its withdrawal as
      well as reinstatement of cocaine-seeking behavior on cell-mediated immunity are
      not well known. Cocaine self-administered for 18 days induced a significant
      increase in spleen weight, plasma corticosterone levels, interleukin (IL)-10, and
      tumor necrosis factor-alpha production, while concanavalin A-stimulated
      proliferation responses of peripheral blood T-lymphocytes and interferon-gamma
      production by splenic lymphocytes were not altered. After 10 days withdrawal from
      cocaine, reinstatement of cocaine seeking behavior induced either by a priming
      dose of the drug (unconditioned stimulus), by cue previously associated with
      cocaine self-administration (conditioned stimuli), or by both these stimuli
      evoked similar changes in several immunological parameters, for example, a
      decrease in relative spleen weight, proliferative activity of splenocytes, and
      their ability to produce IL-10. The results showed that the cue previously
      associated with cocaine suppressed some parameters of cell-mediated immunity to
      the same degree as re-exposure to cocaine. The present study provides the first
      evidence that alterations of immune status can be conditioned by environmental
      stimuli paired with cocaine administration.

PMID- 18719315
TI  - Reactive oxygen species mediate oridonin-induced HepG2 apoptosis through p53,
      MAPK, and mitochondrial signaling pathways.
AB  - Oridonin, a diterpenoid isolated from Rabdosia rubescences, could induce
      apoptosis through the generation of reactive oxygen species (ROS) in human
      hepatoma HepG2 cells. p53, a specific inhibitor of pifithrin alpha (PFT alpha),
      markedly inhibited ROS generation and apoptosis, showing that p53 was responsible
      for the cytotoxity of oridonin through mediation by ROS. Moreover, the ROS
      activated the p38 kinase, which in turn promoted the activation of p53, as
      verified by evidence showing that the ROS scavenger N-acetyl-cysteine (NAC) not
      only blocked the phosphorylation of p38 but also partially inhibited the
      activation of p53, and the p38 inhibitor SB203580 reduced the activation of p53
      as well. Mitochondria were either the sources or the targets of ROS. This study
      showed that oridonin stimulated mitochondrial transmembrane permeabilization in a
      ROS-dependent manner because NAC almost thoroughly reversed the drop of
      mitochondrial transmembrane potential (Deltapsim) and the release of cytochrome c
      from the mitochondrial inter-membrane space into cytosol. Furthermore, as a
      result of mitochondrial permeability transition, procaspases-9 and -3 were
      cleaved into 37- and 17-kDa proteolytic products, respectively, which acted as
      executors of oridonin-induced apoptosis.

PMID- 18719316
TI  - The seed extract of Cassia obtusifolia offers neuroprotection to mouse
      hippocampal cultures.
AB  - The precise causative factors in neurodegenerative diseases such as Alzheimer's
      (AD) and Parkinson's disease remain elusive, but mechanisms implicated comprise
      excitotoxicity, mitochondrial dysfunction, and in the case of AD, the amyloid
      beta peptide (Abeta). Current therapeutic strategies for such disorders are very
      limited; thus, traditional herbal medicines currently receive increased
      attention. The seeds of Cassia obtisufolia have long been used in traditional
      eastern medicine and more recently the ethanolic fraction of the seeds (COE) has
      been shown to attenuate memory impairments in mice. In this study, we set out to
      determine the effect of COE (range: 0.1 - 10 microg/ml) on calcium dysregulation
      and cell death models in mouse primary hippocampal cultures implicated in general
      neurodegenerative processes and in the pathogenesis of AD: excitotoxicity,
      mitochondrial dysfunction, and Abeta toxicity. It was found that treatment with
      COE attenuated secondary Ca2+ dysregulation induced by NMDA (700 microM), while a
      pre-application of COE also reduced NMDA-induced cell death. Furthermore, COE was
      neuroprotective against the mitochondrial toxin 3-NP (1 mM), while having no
      significant effect on cell death induced by incubation with naturally-secreted
      oligomers of Abeta (8.2 pg/ml). Collectively, these results are important for the
      therapeutic use of COE in the treatment of neurodegenerative disorders.

PMID- 18719318
TI  - Thienopyridine resistance among patients undergoing intracoronary stent
      implantation and treated with dual antiplatelet therapy: assessment of some
      modifying factors.
AB  - In this open, prospective study we assessed the prevalence of antiplatelet
      resistance among patients subjected to intracoronary stent implantation. In
      patients treated with aspirin + thienopyridine (N = 32), platelet reactivity
      index (PRI) significantly decreased after 2 and 7 days of dual antiplatelet
      treatment in comparison with the same patients on aspirin monotherapy (P<0.001,
      both). After 7 days of aspirin + thienopyridine treatment, insufficient
      antiplatelet response was observed in 28% (9/32) of the patients. High
      interindividual variability in response to aspirin + thienopyridine treatment
      emphasizes the significance of thienopyridine resistance, while the influence of
      statins on such a treatment should be reassessed.

PMID- 18719317
TI  - Diazepam protects against the enhanced toxicity of cocaine adulterated with
      atropine.
AB  - We examined the toxicity of cocatropine (cocaine/atropine mixture) and the
      therapeutic potential of diazepam on some behavioral and physiological parameters
      in rats. Atropine (20 and 60 mg/kg) or cocaine (40 mg/kg) alone did not induce
      any seizure or death, but the combination significantly increased both, after
      both acute and binge treatment. There was a significant increase of EEG mean
      total spectral power in cocatropine- in comparison with cocaine-treated animals.
      Hyperlocomotion was observed in non-seizuring rats treated with cocaine or
      cocatropine. Cocaine, atropine 60, and cocatropine (40 + 20 and 40 + 60) all
      induced hyperthermic effects in non-seizuring rats, while cocatropine (40 + 60)
      seizuring animals had hypothermia. An initial hypertensive and tachycardiac
      effect within 15 min was followed by a secondary fall in the cocatropine (40 +
      60) group. Cocatropine toxicity was partially or fully reversed by diazepam (5
      mg/kg), given intraperitoneally after the first seizure. The present findings
      provide, for the first time, details of a synergistic toxic effect of the
      cocaine/atropine mixture and of the potential of diazepam for treating
      cocatropine-related hospital emergencies.

PMID- 18719319
TI  - Acute protective effects of simvastatin in the rat model of renal ischemia
      reperfusion injury: it is never too late for the pretreatment.
AB  - Acute pretreatment with a single i.v. bolus injection of simvastatin (1 mg/kg)
      significantly protects rat kidney injured by ischemia-reperfusion (I/R) (45 min +
      6 h). We aimed to determine the optimal timing of such a pretreatment. The
      effects of both injections of simvastatin before ischemia and reperfusion were
      similar regarding total histological score. However, simvastatin injected 30 min
      before ischemia was 30% - 75% more effective in reduction of serum creatinine
      levels and interstitial edema score, while its injections 5 and 30 min before
      reperfusion were 25% - 60% more effective in reduction of tubular necrosis score
      and fractional excretion of Na+. However, the observed differences do not seem to
      offer significant advantage in clinical settings.

PMID- 18719320
TI  - Changes of HCO3-/Cl- exchanger activity during meiotic maturation in Balb/c
      strain mouse oocytes and zygotes.
AB  - Intracellular pH-regulatory mechanisms are acquired by growing mouse oocytes with
      meiotic competence, and these mechanisms become fully active when the oocytes
      develop to the germinal vesicle (GV) stage as shown in CF1 and Balb/c strains
      mice. On the other hand, there is some evidence showing that intracellular pH
      regulatory mechanisms are inhibited at the stages of Metaphase I (MI) and II
      (MII) oocytes in the CF1 strain mouse and hamster. Since it has been shown that
      the intracellular pH regulatory mechanism can be functionally different among
      mouse strains (e.g., CF1, Balb/c), the aim of this study was to investigate the
      activity of HCO3-/Cl- exchanger (anion exchanger, AE), which protects cells
      against alkalosis during the meiotic maturation process, in the GV oocyte up to
      the pronuclear (PN) zygote derived from the Balb/c strain mouse. Intracellular pH
      (pHi) was recorded using a microspectrofluorometric technique during meiotic
      maturation stages. KSOM-based solutions were used as culture and recording
      solutions. AE activity was determined using a Cl- removal assay and was reported
      as the change in pHi per minute. AE activity was high in GV stage oocytes but was
      significantly inhibited at the MI and MII stages. AE activity was higher in the
      PN zygote stage. This activity was significantly inhibited in all oocyte and
      zygote stages by 4,4'-Diisocyanatostilbene-2,2'-disulfonic acid disodium salt.
      After alkalosis induction, the pHi of MI and MII stage oocytes did not completely
      recover; however, almost complete recovery occurred in the GV stage oocytes and
      PN zygotes. These results suggest that AE is inhibited during the meiotic
      maturation process in the Balb/c strain mouse.

PMID- 18719321
TI  - Diffusion-perfusion mismatch in symptomatic vasospasm after subarachnoid
      hemorrhage.
AB  - Diffusion-weighted and perfusion-weighted magnetic resonance (MR) imaging were
      investigated as a method to detect diffusion-perfusion mismatch in the early
      stages of vasospasm in 17 patients with acute subarachnoid hemorrhage after
      aneurysm clipping. Single photon emission computed tomography (SPECT) with N
      isopropyl-p-[(123)I]iodoamphetamine was also performed. Diffusion-perfusion
      mismatch was clearly identified in the 3 patients who manifested clinical
      deterioration. Perfusion-weighted imaging showed increased mean transit time,
      normal cerebral blood flow, and increased or normal cerebral blood volume. SPECT
      revealed no earlier signs of vasospasm. Diffusion-perfusion mismatch was clearly
      demonstrated in the early stages of vasospasm, so may be useful for early
      identification of ischemia in vasospasm and initiating appropriate treatment.

PMID- 18719322
TI  - Repair and regeneration of vertebral body after antero-lateral partial
      vertebrectomy using beta-tricalcium phosphate.
AB  - Antero-lateral partial vertebrectomy (ALPV) was used for decompression in 91
      patients with multilevel cervical disorders. The high-speed drill was used to
      excise about 1/3 of the vertebral body for relief of anterior compression of the
      cord and nerve roots under the operating microscope. The key point was opening of
      the medial wall of the foramen of transverse process at the beginning of the
      ALPV, allowing the determination of the lateral borders of the ALPVs. To repair
      and regenerate the vertebral body, a beta-tricalcium phosphate (beta-TCP) block
      was trimmed into a cuneiform shape and implanted into the sites of the ALPV
      excluding the upper and lowermost vertebral bodies. Postoperative computed
      tomography confirmed that beta-TCP was gradually replaced by newly formed bone
      from the surface towards the center of the block, and that the affected vertebral
      body was remodeled by 6 to 12 months after the implantation of beta-TCP. The
      cortical bone borders on the bone marrow at the site of the regeneration. The
      pedicles on the side of the ALPVs were rebuilt during regeneration of the
      affected vertebrae. Thus, the vertebral foramen of the cervical spine was widened
      in the anterior direction at the levels of the ALPVs, resulting in restoration of
      the physiological size of the cervical cord. The cervical curvature remained
      unchanged and a certain degree of cervical mobility (mean 86%) was preserved in
      this series.

PMID- 18719323
TI  - Pontine infarction induced by injury of the perforating branch of the basilar
      artery after blunt head impact: case report.
AB  - A 77-year-old male pedestrian was hit by a car. On admission, he had disturbance
      of consciousness and left hemiplegia. Computed tomography (CT) indicated only
      left frontal subcutaneous hematoma and minor hemorrhage in the left frontal lobe,
      suggesting axonal injury. CT on hospital day 2 revealed a low density area in the
      right paramedian pons, but CT angiography showed no dissection or occlusion of
      the vertebrobasilar artery. The diagnosis was pontine infarction resulting from
      shearing force injury to the paramedian branch of the basilar artery. He was
      transferred to another hospital for rehabilitation without improvement of
      symptoms on hospital day 51. Paramedian pontine infarction tends to occur in
      patients with risk factors for arteriosclerosis, including hypertension, diabetes
      mellitus, hyperlipidemia, or smoking. The present elderly patient had
      hypertension and hyperlipidemia, so arteriosclerosis in the paramedian branch may
      have contributed to his susceptibility to such injury.

PMID- 18719324
TI  - Traumatic retroclival epidural hematoma in a child: case report.
AB  - An 11-year-old girl presented with a very rare traumatic retroclival epidural
      hematoma manifesting as bilateral abducens nerve palsy, deviation of the uvula to
      the left, and weakened movement of tongue, which developed after a motor vehicle
      accident. The patient was treated conservatively and showed good outcome.
      Retroclival hematoma is a mainly pediatric entity usually associated with
      ligamentous injury at the craniocervical junction, and can be treated
      conservatively with good outcome.

PMID- 18719325
TI  - Central pontine and extrapontine myelinolysis in an infant associated with the
      treatment of craniopharyngioma: case report.
AB  - A 3-year-old girl presented with osmotic demyelination syndrome after undergoing
      uneventful neuroendoscopic cystostomy for a growing cystic suprasellar
      craniopharyngioma following microscopic subtotal resection 1 year previously.
      Endocrinopathy had well been controlled by hormone replacement therapy and
      administration of 1-amino-8-d-arginine-vasopressin with serum sodium
      concentration within the normal range. She presented generalized seizure and
      fever on postoperative day 7, with hyponatremia beginning on postoperative day 4
      and deteriorating despite frequent correction. The serum sodium concentration
      began to fluctuate on the same day, in the range 111-164 mEq/l, which lasted for
      2 weeks, refractory for intense management. Her body temperature also fluctuated
      between hypo- and hyperthermia not correlated with serum inflammatory markers.
      Her conscious disturbance progressively deteriorated with spastic paraparesis.
      T(2)-weighted magnetic resonance (MR) imaging taken on postoperative day 19
      revealed hyperintense areas in the pons, external capsule, bilateral thalami, and
      basal nuclei, which had not been recognized before, suggesting osmotic
      demyelination syndrome causing central pontine and extrapontine myelinolysis. MR
      imaging taken on postoperative days 230 and 360 showed some diminished lesions
      but others persisted and resulted in a cavity. The patient's depressed conscious
      level did not improve. Suprasellar craniopharyngioma with long-standing
      hypothalamic dysfunction may be associated with severe osmotic demyelination
      syndrome even after less invasive surgery, so serum sodium derangement after
      surgery should be promptly corrected even if only subtle signs are present.

PMID- 18719326
TI  - Acute basilar artery occlusion in a patient with left subclavian artery occlusion
      due to first rib anomaly: case report.
AB  - A previously healthy 22-year-old man presented with thoracic outlet syndrome
      manifesting as Raynaud's phenomenon in the left hand and embolic occlusion of the
      basilar artery. Three-dimensional computed tomography angiography showed that the
      left subclavian artery was occluded as it passed over the abnormal first rib.
      Retrograde propagation of the thrombus from the site of arterial occlusion and/or
      reflux of embolic material was suspected. Medical therapy was started. The
      patient underwent resection of the anomalous rib. Postoperative angiography
      demonstrated that the subclavian artery was recanalized with almost normal distal
      flow. The basilar artery was also recanalized. Thoracic outlet syndrome due to a
      first rib anomaly may cause stroke.

PMID- 18719327
TI  - Orbital dermoid cyst with intratumoral inflammatory hemorrhage: case report.
AB  - An 85-year-old female presented with a 3-month history of worsening
      hyperlacrimation and blurred vision following blunt head injury. Her past medical
      history was unremarkable. Her blood examination identified no abnormal findings.
      Neuroophthalmological inspection revealed extraocular movement disorder and mild
      exophthalmos on the affected side. Her visual acuity was not disturbed.
      Neuroimaging showed a cystic mass located extraconally in the superolateral
      compartment of the anterior orbit, without enhancement by contrast medium.
      Surgical exploration resulted in escape of chocolate-colored, liquefied hematoma
      during dissection. No vascular lesion was found. A grayish-white cyst wall was
      found adhering strongly to the lateral and superior rectus muscles. The lacrimal
      gland was not identified. The mass was totally resected. Histological examination
      indicated dermoid cyst with inflammatory interstitial hemorrhage. No component of
      vascular malformation or atypia was found. Hyperlacrimation and extraocular
      movement improved postoperatively. We thought that the previous blunt head injury
      might have induced intratumoral hemorrhage in the preexisting dermoid cyst and
      that the escaped contents caused inflammatory irritation, resulting in the
      hyperlacrimation. Dermoid cyst may show atypical presentation with intratumoral
      hemorrhage and should always be included in the differential diagnosis of orbital
      tumor.

PMID- 18719328
TI  - Osteolytic lumbar discal cyst: case report.
AB  - A 25-year-old man presented with left lumboischialgia refractory to medical
      treatment. Neurological examination revealed L5 and S1 radiculopathy which
      rapidly worsened over a short period. Magnetic resonance imaging demonstrated
      disk bulging with a discal cyst at the L4-5 intervertebral space and disk
      herniation at the L5-S1 intervertebral space. Computed tomography showed
      osteolytic change of the L5 vertebral body adjacent to the cyst. Resection of the
      cyst and removal of the herniated disk were performed following fenestration of
      the L4-5 and L5-S1 interlaminar spaces. Bloody serous fluid followed by clear
      serous fluid was recognized during the aspiration and partial resection of the
      cyst at the L4-5 level. Histological examination demonstrated a cyst wall
      consisting of fibrous connective tissue without a single-layer lining of cells,
      and fibrin deposits. The patient's symptoms disappeared immediately after the
      operation. This osteolytic lumbar discal cyst possibly occurred subsequent to
      hemorrhage from the epidural venous plexus following intervertebral disk injury,
      hematoma encapsulation by connective fibrous tissue, and cyst wall formation in
      reaction to the disk injury and hemorrhage. The cyst may have enlarged due to the
      inflow of the serous fluid from the water-containing degenerated disk.

PMID- 18719329
TI  - Radiculopathy caused by lumbar epidural venous varix: case report.
AB  - A 33-year-old man presented with a rare case of lumbar epidural venous varix
      causing radiculopathy manifesting as sciatica exacerbated during bowel movements.
      The left straight-leg raising test was positive and patellar tendon reflex was
      lost. Lumbar magnetic resonance imaging showed a mass lesion in the epidural
      space at the L4 level just anterior to the dural sac on the left, appearing as
      hypointense on T(1)- and hyperintense on T(2)-weighted images, with ring-like
      enhancement with gadopentetate dimeglumine. He underwent surgery under a
      preoperative diagnosis of cystic nerve sheath tumor. After left hemilaminectomy,
      intraoperative ultrasonography showed a low echoic mass lesion ventral to the L4
      nerve root. The mass was dark blue with a smooth wall. Tearing of the wall
      resulted in continuous bleeding. After removal of the lesion, we confirmed that
      the dura of the nerve root was intact. Histological examination of the surgical
      specimen confirmed venous tissue. The postoperative course was excellent. Lumbar
      epidural varix is difficult to diagnose preoperatively. Lumbar epidural varix
      should be considered if the lesion is smaller on preoperative than intraoperative
      imaging, or disappears with bleeding cessation, as this may avoid unnecessary
      widening of the operative field. The correct preoperative diagnosis remains
      difficult, so we recommend surgical removal and histological confirmation.

PMID- 18719330
TI  - Technique to detect coil migration using mask images of rotational angiography
      during stent-assisted coil embolization for ultra-wide necked aneurysms:
      technical note.
AB  - A novel technique was developed to detect coil migration to the stent interior
      using mask images of rotational angiography. Stent-assisted coil embolization
      under x-ray fluoroscopy control was simulated with a hand-made vessel model. The
      stent interior was observed with a rigid endoscope during coil embolization.
      After insertion of the coil, mask images using rotational angiography were
      acquired and multi-planar reformation (MPR) images were reconstructed on a
      workstation. The stent interior could be observed during coil embolization.
      Longitudinal MPR images showed the positional relationships between the stent,
      coil, and tip of the microcatheter. This technique was successfully employed in a
      patient to detect displacement of the tip of the microcatheter inside the stent.
      This technique is useful for monitoring stent-assisted coil embolization of an
      ultra-wide necked aneurysm, but requires extra time and increased radiation
      exposure, so we recommend use only if coil migration is strongly suspected.

PMID- 18719331
TI  - [Asbestos clinics and asbestos health examinations--findings from a questionnaire
      survey of implementing organizations].
AB  - In June 2005 the press reported that many former employees of a company which
      used asbestos, and individuals who lived near the company's factory, had been
      diagnosed with mesothelioma. This finding triggered concern and alarm in Japan.
      In response, many "asbestos clinics" were formed, and recognized medical
      institutions began to implement asbestos-related health examinations. We
      conducted a nationwide questionnaire survey to evaluate the activities in, and
      the challenges for, these medical institutions. We received 137 valid responses,
      more than half of which were from clinics and hospital-based "asbestos clinics"
      instigated after the "Kubota shock." Among the asbestos exposure history
      interviewing practices, job histories of the interviewee were prioritized, over
      place of residence, and possible exposure of family members. Standard
      questionnaires were utilized by over 70% of respondents. The practitioners
      reported problems with lack of manpower and evaluation of asbestos exposure.
      Examinees consulted attending physicians on a wide range of matters including
      asbestos-related diseases, asbestos exposure, and financial compensation. It is
      predicted that asbestos-related diseases in general, and mesothelioma in
      particular, will increase in the future. Accordingly, early detection and
      treatment should be accorded high priority. The organizations we surveyed have
      important roles to play. Although resources are limited, effective diagnosis and
      treatment are essential, and a system assisting organizations to make accurate
      and efficient identification of asbestos exposure hazards is imperative.

PMID- 18719332
TI  - Delusions and visual hallucinations in dementia patients: focus on personal
      history of the patients.
AB  - Psychotic features are frequently seen in dementia patients, which indeed cast a
      huge psychological and physical burden onto their care givers. This is especially
      true for delusions and hallucinations. If inquired into in greater detail, some
      of the delusions and even hallucinations can be found to arise from plausible
      origins. In this article, the author reports two dementia patients, with an
      attempt to link the unique psychotic features to the personal history of the
      individual patient. In addition to biological predisposition, the background and
      the personal history of each patient may play a role in the development of such
      psychotic features. To emphasize the background of the patients and to treat him
      or her as a person is also the core spirit of medical humanity, which is an issue
      important for dementia care. The author also discusses the two topics: visual
      hallucination in patients with dementia with Lewy bodies and the genetic
      polymorphism of dopamine D2 receptor gene in dementia patients with delusions. If
      clinicians spend more time to understanding the history of their patients, at
      least some of the need to use medical treatment can be reduced.

PMID- 18719333
TI  - Calcium-sensing receptor stimulates luminal K+-dependent H+ excretion in
      medullary thick ascending limbs of Henle's loop of mouse kidney.
AB  - The calcium-sensing receptor (CaSR) is known well as a sensor of extracellular
      calcium for regulating parathyroid hormone secretion. CaSR is located along all
      nephron segments in the kidney. While hypercalcemia strongly enhances urinary
      acidification, the relationship between CaSR and acid-base metabolism in the
      kidney is still uncertain. In the present study, we examined whether CaSR
      activation caused acid secretion in the medullary thick ascending limb (mTAL),
      which is one of the major nephron segments involved in both mineral and acid-base
      regulation. The effects of a potent calcimimetic neomycin (Neo) on intracellular
      pH (pHi) were analyzed in the in vitro miroperfused mouse mTALs. The mTALs were
      incubated with 2,7-bis-(2-carboxyethyl)-5(6)-carboxyfluoresceine
      acetoxymethylester (BCECF-AM) for microfluorescent pHi measurements. In HCO(3)(
      )/CO(2)-buffered solution, the steady-state pHi was 7.17 +/- 0.01 (n = 19).
      Basolateral Neo at 0.4 mM in basolateral side significantly alkalinized the mTAL
      cells to 7.28 +/- 0.02 (n = 19), while Neo in the lumen had no effect on pHi. Neo
      in the basolateral side alkalinized the mTALs in the absence of ambient Na(+) and
      the presence of H(+)-ATPase inhibitor bafilomycin in the lumen, indicating that
      the effect of Neo is unrelated to Na(+)-dependent acid-base transporters such as
      Na(+)-H(+) exchangers and Na(+)-HCO(3)(-) cotransporter, or to luminal H(+)
      ATPase. In contrast, the effect of Neo on pHi was inhibited by K(+) removal or
      treatment with specific H(+)-K(+)-ATPase (HKa) inhibitors, ouabain and Sch-28080,
      in the lumen. Our results suggest that hypercalcemia induces urinary
      acidification partly by stimulating luminal K(+)-dependent H(+)-excretion via
      CaSR in mouse mTALs.

PMID- 18719334
TI  - Elasticity of the supraspinatus tendon-muscle unit is preserved after acute
      tendon tearing in the rabbit.
AB  - Supraspinatus tendon tearing is one of the most common causes of the shoulder
      pain and dysfunction, which often requires a surgical repair. In this situation,
      proximal tendon stump is usually retracted medially from its original insertion.
      For successful reduction of the retracted tendon stump to its original insertion,
      the elasticity of the tendon-muscle unit should be preserved by the time of
      surgery. The purpose of the present study was to clarify the chronological
      changes in the elasticity of the supraspinatus tendon-muscle unit after acute
      tendon tearing to determine the optimal timing for the surgery. Right
      supraspinatus tendon was detached (detached side) in 40 male Japanese white
      rabbits, with left shoulders served as controls (control side). Eight animals
      were euthanized at 3 days and 1, 2, 4, or 8 weeks after surgery. Tissue sound
      speed that closely correlates to its elasticity was measured with a scanning
      acoustic microscope. In the supraspinatus tendon, tissue sound speed at 3 days
      after surgery was 1691.1 m/s, compared to 1714.3 m/s at the control side, but the
      difference was not statistically significant at any postoperative time period up
      to 8 weeks. In the supraspinatus muscle, tissue sound speed was not affected at
      all by the detachment of the tendon. The present study indicated that the
      elasticity of the supraspinatus tendon-muscle unit was well preserved for 8 weeks
      after the detachment. In the clinical practice, the retracted supraspinatus
      tendon stump could be repaired without excessive tension by 8 weeks from the
      acute tendon tearing.

PMID- 18719335
TI  - Ras-mediated up-regulation of survivin expression in cytokine-dependent murine
      pro-B lymphocytic cells.
AB  - Survivin, a member of the inhibitor of apoptosis protein (IAP) family, has been
      widely studied because of its aberrant expression in human cancer. Survivin has
      multiple functions, including cell-cycle regulation at mitosis, inhibition of
      apoptosis and caspase-independent cytoprotection. Clinical studies have shown
      that survivin is associated with resistance to treatment and its expression is
      linked to poor prognosis. Recent studies indicated that Ras pathways up-regulate
      survivin expression in hematopoietic cells. Here we analyzed downstream pathways
      of Ras in interleukin-3 (IL-3)-dependent Baf-3 murine-derived pro-B lymphocytic
      cells that express constitutively active Ras mutants, using signaling pathway
      specific inhibitors. Both mitogen-activated protein kinase (MAPK) and
      phosphatidylinositol-3 kinase (PI3-K) pathways are involved in the induction of
      survivin. Downstream of PI3-K, the signaling pathway is composed of two kinases,
      Akt and mammalian target of rapamycin (mTOR) pathways. In the downstream targets
      of PI3-K, mTOR but not Akt is responsible for survivin expression. Using a
      counterflow centrifugal elutriator, we observed G2/M phase-dominant survivin
      expression in Baf-3 cells. Interestingly, constitutively active Ras mutants also
      induced survivin in a cell cycle-dependent manner. Reporter assays of the
      survivin gene promoter revealed a transcriptional regulatory cis-acting region
      that is responsible for Ras signaling, indicating that Ras increases the
      transcription of the survivin gene through specific enhancer elements. These data
      illustrate the pathways regulating survivin expression by Ras. Ras activates the
      MAPK, PI3-K and mTOR pathways, and these signals enhance survivin transcription.
      Our data will provide the new information about mechanisms of survivin expression
      by Ras-signalling pathways.

PMID- 18719336
TI  - Growth inhibitory effect of Kruppel-like factor 6 on human prostatic carcinoma
      and renal carcinoma cell lines.
AB  - Kidney and prostate cancers are leading causes of death in the world, and
      accumulating evidence suggests that tumor suppressor gene, Kruppel-like factor 6
      (KLF6), plays an important role in both the development and the progression of
      cancer. However, the effect of wild type KLF6 (wtKLF6) on the growth potential of
      renal carcinoma cells has not been examined. In the present study, we therefore
      introduced wtKLF6 gene into a prostatic carcinoma derived cell line, DU145, and a
      renal carcinoma derived cell line, OS-RC-2, and have established DU145-KLF6 and
      OS-RC-2-KLF6 cell lines, both of which stably over-express KLF6. Compared with
      vector-transfected cell lines (control cells), the wtKLF6-transfected cell lines
      showed the lower proliferation capacity (p < 0.01) and higher percentages of
      cells with apoptotic signals (p < 0.01). Moreover, the KLF6-overexpressed cell
      lines showed significant increases in the cell population at G0/G1 phase and
      significant decreases in the cell population at S and G2/M phases. There was no
      significant difference in the results of the cell cycle analysis between the two
      KLF6-overexpressed cell lines, DU145-KLF6 and OS-RC-2-KLF6. The cyclin-dependent
      kinase inhibitor p21 as a transcriptional target of the KLF6 gene was also
      studied. The expression levels of p21 mRNA and protein were up-regulated in both
      KLF6-overexpressed cell lines. These results indicate that the wtKLF6 gene
      effectively inhibited the growth of the prostatic carcinoma DU145 and renal
      carcinoma OS-RC-2 cell lines, probably through up-regulation of p21. Thus, KLF6
      may represent a novel therapeutic target for inhibiting prostate and renal
      cancer.

PMID- 18719337
TI  - Early diagnosis of cancer by detecting the chemiluminescence of hematoporphyrins
      in peripheral blood lymphocytes.
AB  - Early detection and optimal treatment are the most effective means to improve
      cancer mortality. Mass screening for cancer has yielded a marked reduction of
      cancer mortality in the United States. Simple and effective methods are expected
      for screening of malignancy. Hematoporphyrin derivatives (HPDs) are known to
      accumulate in cancer cells; thus, HPD has been used for local diagnosis and
      photodynamic therapy of cancer. The lymphocytes of cancer patients also
      demonstrate the active uptake of HPD and this phenomenon has been applied for the
      diagnosis of cancer. In the present study, we have developed a novel method for
      measurement of the chemiluminescence of HPD in peripheral blood lymphocytes. HPD
      is composed of hematoporphyrin and its oligomers. Seven cancer patients and seven
      controls were recruited for this study. The primary cancers included two prostate
      cancers (one without metastasis and the other with lung metastasis), a renal
      cancer, a lung adenocarcinoma with systemic metastasis, two gallbladder cancers
      with lung metastasis, and a colon cancer with liver metastasis. HPD in
      lymphocytes was measured using a highly sensitive chemiluminescence analyzer with
      laser light irradiation to detect photoemission by (1)O(2) from HPD. The
      intensity of chemiluminescence exhibited a linear correlation with the
      concentrations of HPD. In addition, the level of HPD in lymphocytes was
      significantly higher in cancer patients than that in healthy volunteers (p <
      0.05). These results suggest that detection of the chemiluminescence of HPD in
      lymphocytes could be a sensitive and simple method for cancer diagnosis and
      screening.

PMID- 18719338
TI  - The non-steroidal anti-inflammatory drugs protect mouse cochlea against acoustic
      injury.
AB  - Acoustic injury is a common cause of hearing loss for people in industrial
      societies. Cyclooxygenase (COX) and lipoxygenase (LOX) are two important enzymes
      involved in arachidonic acid metabolism. Two COX isozymes are characterized, COX
      1 and COX-2, that differ in terms of regulatory mechanisms of expression.
      Although COX-1, COX-2, and LOX are expressed in cochlea, their roles played in
      cochlear acoustic injury have not fully been evaluated. Non-steroidal anti
      inflammatory drugs (NSAIDs) inhibit either COX or LOX, or both. This study
      evaluated the effects of NSAIDs on the functional recovery of the cochlea after
      acoustic injury. Mice were exposed to a 4-kHz pure tone of 128 dB SPL (sound
      pressure level) for 4 hours and received one of the following drugs for two weeks
      after acoustic overexposure: indomethacin (COX-1 inhibitor), meloxicam, SC58125,
      and CAY10404 (COX-2 inhibitors), and nordihydroguaiaretic acid (LOX inhibitor).
      The hearing ability was evaluated using an auditory brainstem response (ABR)
      before and after overexposure. The ABR threshold shifts, defined as subtraction
      between ABR thresholds before and after overexposure, were compared among the
      control and the medication groups at one and two weeks after acoustic
      overexposure. Treatment of mice with either indomethacin or nordihydroguaiaretic
      acid decreased the ABR threshold shifts after overexposure, indicating that COX-1
      and LOX inhibitors exhibited protective effects against acoustic injury. In
      contrast, COX-2 inhibitors, meloxicam, SC58125, and CAY10404, showed no
      noticeable effects on the ABR threshold shifts. These findings suggest that COX-1
      and LOX are involved in the pathogenesis of acoustic injury in cochlea.

PMID- 18719339
TI  - Sepsis is characterized by the increases in percentages of circulating CD4+CD25+
      regulatory T cells and plasma levels of soluble CD25.
AB  - The function of immune system is to protect hosts from invading microorganisms by
      destroying infected cells while minimizing damage to tissues. Among immune cells,
      CD4(+)CD25(+) regulatory T cells (Treg cells) control immune responses by
      limiting infectious processes. However, it remains unclear whether Treg cells are
      induced in systemic inflammatory response syndrome (SIRS) or infectious SIRS
      (i.e. sepsis). SIRS and sepsis are associated with stressful inflammatory
      conditions. We therefore measured CD25(+) T cells and circulating CD4(+) T cells,
      along with plasma levels of CD25, interleukin (IL)-6, and IL-10, in 20 septic
      patients (64 +/- 11 years), 16 SIRS patients (59 +/- 16 years), and control
      subjects: 13 elderly (60 +/- 16 years) and 14 young volunteers (28 +/- 3 years).
      Septic patients (23.3 +/- 11.8%, p < 0.01) showed significantly higher
      percentages of CD25(+) cells among CD4(+) T cells (i.e. Treg cells) than did
      either young (10.6 +/- 3.7%) or elderly volunteers (11.1 +/- 3.8%). The
      percentages of Treg cells in septic patients were higher than those in SIRS
      patients (12.4 +/- 6.9%, p < 0.01). Moreover, plasma levels of soluble CD25 were
      significantly higher in septic patients, compared to the levels in SIRS patients
      or volunteers (p < 0.01). No significant difference in plasma levels of IL-6 or
      IL-10 was found between septic patients and SIRS patients. Thus, sepsis is
      associated with the increased percentages of Treg cells and elevated plasma level
      of soluble CD25. The elevation of these parameters might be a useful marker of
      infections in SIRS.

PMID- 18719340
TI  - Low prevalence of metabolic syndrome and its components in rural Japan.
AB  - Tsunan, Niigata is a non-westernized rural Japanese town, known for heavy
      snowfalls and as a rice-producing area, whose inhabitants have a long life
      expectancy. We investigated the prevalence of obesity, metabolic syndrome (MetS)
      and its components in Tsunan. A total of 1,155 men and women, 40-69 years of age
      were recruited from participants in the 2005 public-health program in Tsunan.
      Obesity was defined as body-mass index (BMI) >or= 25 kg/m(2). MetS was defined as
      BMI >or= 25 kg/m(2) as well as at least two of the following three items: (1)
      high glycosylated hemoglobin (HbA1c >or= 5.5%); (2) high blood pressure (HBP:
      systolic blood pressure >or= 130 mmHg or diastolic blood pressure >or= 85 mmHg),
      and (3) low high-density lipoprotein cholesterol (HDL-C < 40 mg/dL). If an
      individual was diagnosed with diabetes, hypertension, or dyslipidemia, each item
      was recorded as a positive finding. The prevalence of MetS and its components
      among Tsunan inhabitants were compared to the results of the 2005 Japanese
      nationwide survey. The prevalence of MetS was 4.6% in males and 4.2% in females.
      The prevalence of obesity, high HbA1c, HBP, and low HDL-C were 22.1/22.2%,
      13.4/16.4%, 46.6/40.0%, and 9.2/3.9% in males/females, respectively. All values
      were significantly lower than the national results, except for the rate of female
      obesity. The lower prevalence of MetS and its components in Tsunan may be due to
      the consumption of traditional Japanese food, which is still commonly eaten
      there, and the higher levels of regular physical activity of farmers.

PMID- 18719341
TI  - Lung fibrosis 10 years after cessation of bleomycin therapy.
AB  - Bleomycin (BLM) is a chemotherapeutic agent used for the treatment of several
      types of malignancy, including germ cell tumors, lymphoma, and certain types of
      squamous-cell carcinoma. The common adverse effect of BLM is interstitial
      pneumonitis, followed by pulmonary fibrosis. BLM-induced pneumonitis occurs in up
      to 46% of patients treated with BLM-containing chemotherapy and lung toxicity
      usually appears during treatment. Here we describe a patient with lung fibrosis,
      who presented with slow progressive breathlessness and pneumothorax more than 10
      years after cessation of BLM therapy. A 15 year-old girl presented with abnormal
      shadows on chest X-ray. The patient had a yolk sac carcinoma in the sacral region
      at 1 year of age and obtained complete remission after being treated with tumor
      resection, radiation, and several anti-cancer drugs including BLM. There were no
      abnormal findings in chest X-ray until she reached 3 years of age, when she had
      developed respiratory distress that worsened with age. The patient had
      experienced an episode of pneumothorax at 13 years of age. Chest CT at the time
      revealed interstitial reticular opacities. Radiological findings and pathological
      examination of the lung tissue obtained during bullectomy with video-assisted
      thoracic surgery were compatible with BLM-induced pneumonitis. The present study
      suggests that lung fibrosis may surface more than 10 years after cessation of BLM
      therapy at the age of 1 year, with no chest radiographic findings 1 year after
      completion of chemotherapy. The use of BLM in infants requires strict supervision
      and observation and careful long-term follow up.

PMID- 18719342
TI  - A novel needle-type sampling device for flexible ultrathin bronchoscopy.
AB  - Diagnosis of suspected cancer in the periphery of the lung is difficult. A
      flexible ultrathin bronchoscope has been developed for the diagnosis of
      peripherally located pulmonary lesions that cannot be reached with the sampling
      devices for standard flexible bronchoscopes. The diagnostic yield with forceps
      and a brush for ultrathin bronchoscopes, however, is not adequate, especially
      when a lesion is not exposed to the bronchial lumen. We have thus developed a
      novel needle-type sampling device and tested its yield in transbronchial
      cytology. The device consists of an elongated dental H-file (0.4 mm in diameter
      and 110 cm in length), a housing sheath (1.0 mm in outer diameter), and a novel
      handle, which enables rapid out-and-in motion of the needle. Ten consecutive
      patients with a peripheral pulmonary lesion who had an indication for diagnostic
      procedure with a flexible ultrathin bronchoscope were enrolled. The optimal
      bronchial route to the lesion was analyzed with virtual bronchoscopy in a data
      set obtained with high-resolution computed tomography, and a novel bronchial
      route labeling system (prior-ridge-based relative orientation nomenclature) was
      employed to guide insertion of the bronchoscope. Sampling with the novel needle
      was performed prior to use of the forceps and brush under conventional
      fluoroscopy. In all the cases, sampling with the needle was successful and the
      amount of the specimen was sufficient for cytology. Our novel sampling system
      with flexible ultrathin bronchoscopes may contribute to accurate and minimally
      invasive diagnosis of peripheral pulmonary lesions.

PMID- 18719343
TI  - The prevalence of probable delayed-sleep-phase syndrome in students from junior
      high school to university in Tottori, Japan.
AB  - Delayed sleep phase syndrome (DSPS) is a circadian rhythm sleep disorder with a
      typical onset in the second decade of life. DSPS is characterized by the sleep
      onset insomnia and the difficulty in waking at the desired time in the morning.
      Although DSPS is associated with inability to attend school, the prevalence has
      been controversial. To elucidate a change in the prevalence of DSPS among young
      population, epidemiological survey was conducted on Japanese students. A total of
      4,971 students of junior high school, senior high school, and university were
      enrolled in this cross sectional study in Tottori Prefecture. They answered
      anonymous screening questionnaire regarding school schedule, sleep hygiene and
      symptomatic items of sleep disorders. The prevalence of probable DSPS was
      estimated at 0.48% among the total subject students without gender difference. In
      university, the prevalence of the last year students showed the highest value
      (1.66%), while that of the first year students showed the lowest value (0.09%)
      among all school years from junior high school to university. The prevalence
      increased with advancing university school years. Thus, a considerable number of
      Japanese students are affected with DSPS. Senior students of university are more
      vulnerable to the disorder than younger students. Appropriate school schedule may
      decrease the mismatch between the individual's sleep-wake cycle and the school
      schedule. Promotion of a regular sleep habit is necessary to prevent DSPS among
      this population.

PMID- 18719344
TI  - Thirteen-month registration of patients with gastroenteropancreatic endocrine
      tumours in France.
AB  - The prevalence, clinical profiles and management of gastroenteropancreatic
      endocrine tumours (GEP) in France are not known. From August 1, 2001 to September
      1, 2002, standardized records on patients with GEP were prospectively completed
      in 87 participating centres. The total group amounted to 668 patients (median
      age: 56 years, range: 12-89). WHO performance status was 0/1 for 80.2% of
      patients. The primary sites were the small bowel and colon (288), pancreas (211),
      unknown (77), stomach (33), non-digestive primary sites (24), appendix (20),
      rectum-anus (12), and oesophagus or cardia (3). GEP were functional in 260
      patients (39%). Most pancreatic tumours were non-functional (72%). Metastatic
      disease was observed in 73.4% of cases. Most tumours (85.8%) were well or
      moderately differentiated. Somatostatin receptor scintigraphy was performed in
      only 55% of patients. The following treatment modalities were employed: resection
      of primary tumour: 66%; systemic chemotherapy: 41%; somatostatin analogues: 44
      and 26% for GEP of small intestine and pancreas, respectively; interferon: 12%,
      and intra-arterial hepatic (chemo)embolization in 23 and 15% of GEP arising from
      the midgut and pancreas, respectively. Despite their low prevalence, well
      differentiated GEP represent a significant and heterogeneous clinical group,
      which warrants improved medical education, referral to expert centres at an early
      stage, and the design of prospective therapeutic trials.

PMID- 18719345
TI  - Therapeutic aspects of hepatitis C in hemodialysis patients.
AB  - BACKGROUND: Since hemodialysis (HD) patients usually suffer from multiple
      clinical problems and drug side effects, the treatment of hepatitis C in these
      patients still remains a challenging problem. METHODS: We identified eligible
      studies using a wide-spectrum search up to May 2007 in MEDLINE (since 1966) and
      EMBASE (since 1980). Two researchers (S.M.H.M. and M.R.) independently reviewed
      the manuscripts identified by the search strategy. To determine the most current
      information, only studies that had been published after 1995 were included.
      RESULTS: Interferon (IFN)-alpha has long been used for this purpose; however,
      more recently the advent of pegylated (PEG) IFN has proven to be more beneficial
      in these patients. Even though the usage of ribavirin is promising in the case of
      hepatitis C in otherwise healthy subjects, the utilization of this drug in
      patients with renal failure may be accompanied by catastrophic complications.
      CONCLUSION: Although both conventional IFN and PEG-IFN seem to be favorable
      options for the management of hepatitis C in HD patients, further studies on new
      therapeutic agents are required.

PMID- 18719346
TI  - Elevated cardiac troponin T predicts cardiovascular events in asymptomatic
      continuous ambulatory peritoneal dialysis patients without a history of
      cardiovascular disease.
AB  - BACKGROUND: Recent studies revealed that elevated cardiac troponin T (cTnT) could
      predict all-cause mortality and cardiovascular diseases in end-stage renal
      disease patients. This study aimed to evaluate cTnT as a prognostic value in
      asymptomatic continuous ambulatory peritoneal dialysis patients. METHODS: This is
      a prospective observational study with 107 prevalent peritoneal dialysis
      patients. cTnT, high-sensitive C-reactive protein (hsCRP) and IL-6 were measured
      at baseline. Based on cTnT level, patients were classified as higher cTnT group
      (HT, n = 21, cTnT > or =0.1 ng/ml) and lower cTnT group (LT, n = 86, cTnT <0.1
      ng/ml), and were followed for 3 years. Primary endpoint was cardiovascular
      events. RESULTS: The HT group had a significantly higher level of log hsCRP and
      log IL-6 than the LT group (p < 0.05). Kaplan-Meier survival demonstrated worse
      cardiovascular event-free survival for the HT group. Multivariate analysis
      adjusted for age, cTnT, IL-6 and hsCRP level revealed that age (per 1-year
      increase, HR 1.07, p < 0.05), elevated cTnT (vs. <0.1 ng/ml, HR 5.89, p < 0.05)
      and hsCRP (vs. <3.0 mg/l, HR 4.15, p < 0.05) were identified as significant
      determinants of cardiovascular events. CONCLUSION: This study suggests that cTnT
      may be an aid in risk stratification of continuous ambulatory peritoneal dialysis
      patients.

PMID- 18719347
TI  - Long-term assessment of electrocardiographic and echocardiographic findings in
      Norwegian elite endurance athletes.
AB  - OBJECTIVES: The long-term outcome and clinical significance of athlete's heart
      has been debated and more longitudinal data are needed. We present a prospective
      15 years' follow-up study of ECG and echo findings in elite endurance athletes
      following the end of their competitive career. METHODS: Clinical evaluation, ECG,
      ambulatory Holter recording and echocardiography were performed in 30 top-level
      endurance athletes with a mean age of 24 years with follow-up 15 years later. All
      had then ended their competitive career, but still performed recreational sports
      activities. RESULTS: No clinical events were reported. Average resting heart rate
      was unchanged (53.5 +/- 10 at baseline and 55.4 +/- 11 at follow-up, p = n.s.),
      complex ventricular arrhythmias did not occur and the number of ventricular
      premature beats (VPBs) were 0.4 +/- 0.8/h at baseline and 3.8 +/- 10/h at follow
      up (p = n.s.). In a subgroup of 4 subjects with >100 VPBs per hour at follow-up
      left ventricular mass was increased compared to the others (p < 0.03).
      Furthermore, regression of sino-atrial (SA) and atrioventricular (AV) blocks was
      shown. There were no cases of atrial flutter or fibrillation. There was a slight
      reduction in mean left ventricular wall thickness (9.9 +/- 1.2 vs. 9.5 +/- 1.4
      mm, p < 0.05) and a highly significant reduction of relative wall thickness (0.38
      vs. 0.35, p < 0.001). Left ventricular end-diastolic volume (68 +/- 6 vs. 70 +/-
      7 ml ml/m(2), p = n.s.) and left ventricular mass (109 +/- 19 vs. 107 +/- 19
      g/m(2), p = n.s.) were unchanged when corrected for body surface area and
      ejection fraction (EF) increased (60 +/- 7 vs. 67 +/- 6%, p < 0.01). Parameters
      of left ventricular diastolic function were normal both at baseline and follow
      up. CONCLUSIONS: There was no evidence of deleterious cardiac effects of previous
      top-level endurance athletic activity at 15 years' follow-up.

PMID- 18719348
TI  - A multicenter, phase I dose-escalating study of docetaxel, cisplatin and S-1 for
      advanced gastric cancer (KDOG0601).
AB  - OBJECTIVE: This dose-escalation study of a combination of docetaxel, cisplatin
      and S-1 investigated the dose-limiting toxicity (DLT), maximum-tolerated dose
      (MTD), recommended dose (RD) and antitumor activity in advanced gastric cancer.
      PATIENTS AND METHODS: Patients received docetaxel (40 mg/m(2)), cisplatin (DIV on
      day 1) and S-1 (40 mg/m(2) p.o., twice daily, on days 1-14 every 28 days). The
      starting dose of cisplatin was 60 mg/m(2) (level 1); the dose was escalated to 70
      (level 2) and 80 mg/m(2) (level 3) in a stepwise fashion. RESULTS: Fourteen
      patients were enrolled. The MTD of cisplatin was 80 mg/m(2) (level 3). DLT was
      grade 3 diarrhea, febrile neutropenia and delayed resumption of treatment. The RD
      of cisplatin was considered to be 70 mg/m(2) (level 2). DLT was liver
      dysfunction, occurring in only 1 patient at level 2. The response rate was 69.2%
      (9/13). CONCLUSIONS: For combined treatment with docetaxel, cisplatin and S-1 in
      patients with advanced gastric cancer, RD were docetaxel 40 mg/m(2), cisplatin 70
      mg/m(2) and S-1 80 mg/m(2)/day. This regimen yields a high rate of tumor response
      and can be administered safely. Phase II studies of this regimen are under way.

PMID- 18719349
TI  - Combination therapy of oral fluoropyrimidine anticancer drug S-1 and interferon
      alpha for HCC patients with extrahepatic metastases.
AB  - PURPOSE: There is no standard treatment for hepatocellular carcinoma (HCC)
      patients with extrahepatic metastases. We assessed the efficiency and safety of
      the oral fluoropyrimidine anticancer drug S-1 combined with interferon alpha (IFN
      alpha) for HCC patients with extrahepatic metastases. METHODS: Twenty-nine HCC
      patients with extrahepatic metastases received S-1/IFN. One cycle of combination
      therapy represented 2 weeks followed by 2-4 weeks of rest. In each cycle, S-1 was
      administrated orally at 80-120 mg (depending on body surface area) every day and
      IFN-alpha intramuscularly at 5 million units thrice weekly. RESULTS: The overall
      response of 29 patients was complete response (CR) in 4 (14%), partial response
      (PR) in 1, stable disease in 4, progressive disease in 12, and dropout in 8
      patients. Objective response (CR + PR) was 17%. The time to progression and
      survival rate were significantly higher in patients with lung metastases (n = 19)
      than in those with painful bone metastases (n = 7; p = 0.0058 and 0.0015). With
      regard to NCI-CTC grade 3 adverse reactions, 3 (10%), 3 (10%) and 2 (7%) patients
      developed anorexia, leukopenia, and neutropenia, respectively. No grade 4 adverse
      reaction or toxicity-related death occurred. CONCLUSION: S-1/IFN is a potentially
      safe and suitable combination therapy for HCC patients with extrahepatic
      metastases, especially those with lung metastases.

PMID- 18719350
TI  - Overexpression of tyrosine kinase B protein as a predictor for distant metastases
      and prognosis in gastric carcinoma.
AB  - OBJECTIVE: Tyrosine kinase B (TrkB) is associated with aggressive behavior and
      poor prognosis in various cancers. Here we examined the association between TrkB
      expression and distant metastases/prognosis in gastric carcinoma (GC). PATIENTS
      AND METHODS: We analyzed TrkB expression in 161 GC patients by
      immunohistochemistry and Western blot analysis. The correlation of TrkB mRNA and
      protein expression levels was examined in 10 patients by RT-PCR assay. RESULTS:
      TrkB expression was of level 1 in 97 (60.2%) and level 2 in 64 (39.8%) patients.
      Patients with level 2 expression had a significantly higher incidence of distant
      metastases (p < 0.0001), well-differentiated tumors (p < 0.005), deeper depth of
      invasion (p < 0.005) and poorer disease-free and overall survival (p < 0.0001
      each) compared to patients with level 1. Multivariate analysis identified the
      level of TrkB expression as an independent prognostic factor for both disease
      free and overall survival (p < 0.01 and p < 0.0001, respectively). Both lymph
      node metastasis (odds ratio = 10.7) and TrkB expression (odds ratio = 9.3) were
      independent predictors of distant metastases. CONCLUSION: A high level of TrkB
      expression was observed in well-differentiated GC subtypes and is a predictor for
      distant metastases and prognosis in GC.

PMID- 18719351
TI  - Stimulation of proliferation of U138-MG glioblastoma cells by gastrin-releasing
      peptide in combination with agents that enhance cAMP signaling.
AB  - Increasing evidence indicates that gastrin-releasing peptide (GRP) acts as an
      autocrine growth factor for brain tumors. However, it remains unclear whether the
      cAMP/protein kinase A (PKA) signaling pathway plays a role in mediating the
      mitogenic effects of GRP. We show here that GRP combined with agents that
      stimulate the cAMP/PKA pathway promotes proliferation of human gliobastoma cells.
      Treatment with GRP combined with the adenylyl cyclase activator forskolin, the
      cAMP analog 8-Br-cAMP or the phosphodiesterase type IV inhibitor rolipram
      increased proliferation of U138-MG cells in vitro measured by MTT assay. None of
      the compounds had an effect when given alone. GRP receptor (GRPR) mRNA and
      protein expression in U138-MG cells was detected by reverse transcriptase
      polymerase chain reaction (RT-PCR) and immunohistochemistry. The results suggest
      that GRP and the GRPR interact with the cAMP/PKA signaling pathway in stimulating
      cancer cell proliferation.

PMID- 18719352
TI  - Curcumin inhibits osteoclastogenesis by decreasing receptor activator of nuclear
      factor-kappaB ligand (RANKL) in bone marrow stromal cells.
AB  - Curcumin (diferuloylmethane), a pigment derived from turmeric, has anti-oxidant
      and anti-inflammatory activities. Accumulating evidence points to a biochemical
      link between increased oxidative stress and reduced bone density. Osteoclast
      formation was evaluated in co-cultures of bone marrow stromal cells (BMSC) and
      whole bone marrow cells (BMC). Expression of receptor activator of nuclear factor
      kappaB ligand (RANKL) was analyzed at the mRNA and protein levels. Exposure to
      curcumin led to dose-dependent suppression of osteoclastogenesis in the coculture
      system, and to reduced expression of RANKL in IL-1alpha-stimulated BMSCs.
      Addition of RANKL abolished the inhibition of osteoclastogenesis by curcumin,
      whereas the addition of prostaglandin E2(PGE2) did not. The decreased
      osteoclastogenesis induced by curcumin may reduce bone loss and be of potential
      benefit in preventing and/or attenuating osteoporosis.

PMID- 18719353
TI  - Induction of the nuclear proto-oncogene c-fos by the phorbol ester TPA and v-H
      Ras.
AB  - TPA is known to cooperate with an activated Ras oncogene in the transformation of
      rodent fibroblasts, but the biochemical mechanisms responsible for this effect
      have not been established. In the present study we used c-fos promoter-luciferase
      constructs as reporters, in transient transfection assays, in NIH3T3 cells to
      assess the mechanism of this cooperation. We found a marked synergistic
      interaction between TPA and a transfected v-Ha-ras oncogene in the activation of
      c-fos promoter and SRE. SRE has binding sites for TCF and SRF. A dominant
      negative Ras (ras-N17) inhibited the TPA-Ras synergy by blocking the PKC-MAPK-TCF
      pathway. Dominant-negative RhoA and Rac1 (but not Cdc42Hs) inhibited the TPA-Ras
      synergy by blocking the Ras-Rho-SRF signaling pathway. Constitutively active
      PKCalpha and PKCepsilon showed synergy with v-Ras. These results suggest that the
      activation of two distinct pathways such as Ras-Raf-ERK-TCF pathway and Rho-SRF
      pathway are responsible for the induction of c-fos by TPA and Ras in mitogenic
      signaling pathways.

PMID- 18719354
TI  - Estrogen receptor-alpha mediates the effects of estradiol on telomerase activity
      in human mesenchymal stem cells.
AB  - Sex steroid hormone receptors play a central role in modulating telomerase
      activity, especially in cancer cells. However, information on the regulation of
      steroid hormone receptors and their distinct functions on telomerase activity
      within the mesenchymal stem cell are largely unavailable due to low telomerase
      activity in the cell. In this study, the effects of estrogen (E2) treatment and
      function of estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta)
      on telomerase activity were investigated in human mesenchymal stem cells (hMSCs).
      Telomerase activity and mRNA expression of the catalytic subunit of telomerase
      (hTERT) were upregulated by treatment of the cells with E2. The protein
      concentration of ERalpha was also increased by E2 treatment, and enhancement of
      ERalpha accumulation in the nucleus was clearly detected with
      immunocytochemistry. When ERalpha expression was reduced by siRNA transfection
      into hMSCs, the effect of E2 on the induction of hTERT expression and telomerase
      activity was diminished. In contrast, the transient overexpression of ERalpha
      increased the effect of E2 on the expression of hTERT mRNA. These findings
      indicate that the activation of hTERT expression and telomerase activity by E2 in
      hMSCs depends on ERalpha, but not on ERbeta.

PMID- 18719355
TI  - A novel human BTB-kelch protein KLHL31, strongly expressed in muscle and heart,
      inhibits transcriptional activities of TRE and SRE.
AB  - The Bric-a-brac, Tramtrack, Broad-complex (BTB) domain is a protein-protein
      interaction domain that is found in many zinc finger transcription factors. BTB
      containing proteins play important roles in a variety of cellular functions
      including regulation of transcription, regulation of the cytoskeleton, protein
      ubiquitination, angiogenesis, and apoptosis. Here, we report the cloning and
      characterization of a novel human gene, KLHL31, from a human embryonic heart cDNA
      library. The cDNA of KLHL31 is 5743 bp long, encoding a protein product of 634
      amino acids containing a BTB domain. The protein is highly conserved across
      different species. Western blot analysis indicates that the KLHL31 protein is
      abundantly expressed in both embryonic skeletal and heart tissue. In COS-7 cells,
      KLHL31 proteins are localized to both the nucleus and the cytoplasm. In primary
      cultures of nascent mouse cardiomyocytes, the majority of endogenous KLHL31
      proteins are localized to the cytoplasm. KLHL31 acts as a transcription repressor
      when fused to GAL4 DNA-binding domain and deletion analysis indicates that the
      BTB domain is the main region responsible for this repression. Overexpression of
      KLHL31 in COS-7 cells inhibits the transcriptional activities of both the TPA
      response element (TRE) and serum response element (SRE). KLHL31 also
      significantly reduces JNK activation leading to decreased phosphorylation and
      protein levels of the JNK target c-Jun in both COS-7 and Hela cells. These
      results suggest that KLHL31 protein may act as a new transcriptional repressor in
      MAPK/JNK signaling pathway to regulate cellular functions.

PMID- 18719357
TI  - Nucleolar p19ARF, unlike mitochondrial smARF, is incapable of inducing p53
      independent autophagy.
AB  - ARF mRNA encodes two distinct proteins, the nucleolar p19(ARF), and a shorter
      mitochondrial isoform, named smARF. Inappropriate proliferative signals generated
      by proto-oncogenes, such as c-Myc and E2F1, can elevate both p19(ARF) and smARF
      proteins. The two ARF isoforms differ not only in their localization but also in
      their functions. Nucleolar p19(ARF) inhibits cell growth mainly by activating p53
      or by inhibiting ribosomal biogenesis. In contrast, mitochondrial smARF can
      induce dissipation of the mitochondrial membrane potential and autophagy in a p53
      independent manner. Recently, it was proposed by Abida et al., that similar to
      smARF, the nucleolar p19(ARF) can also induce p53 independent autophagy, but in
      contrast to smARF it does so from within the nucleolus. Our current work shown
      here indicates, however, that if the ectopic expression of p19(ARF) is restricted
      to the nucleolus it cannot induce autophagic vesicle formation. Only upon extreme
      overexpression, when p19(ARF) is localized to extra nuclear compartments, can it
      trigger p53-independent autophagic vesicle formation. Thus, our experiments
      indicate that the nucleolar p19(ARF) is incapable of inducing autophagy from
      within the nucleolus.

PMID- 18719356
TI  - Regulation of autophagy by ceramide-CD95-PERK signaling.
AB  - The manuscripts by Park et al. and Zhang et al. were initially planned as studies
      to understand the regulation of cell survival in transformed cells treated with
      sorafenib and vorinostat, and in primary hepatocytes treated with a bile
      acid+MEK1/2 inhibitor. In both cell systems we discovered that the toxicity of
      sorafenib and vorinostat or bile acid+MEK1/2 inhibitor exposure depended on the
      generation of ceramide and the ligand-independent activation of the CD95 death
      receptor, with subsequent activation of pro-caspase 8. We noted, however, in
      these systems that, in parallel with death receptor-induced activation of the
      extrinsic pathway, CD95 signaling also promoted increased phosphorylation of PKR
      like endoplasmic reticulum kinase (PERK) and eIF2alpha, increased expression of
      ATG5, and increased processing of LC3 and vesicularization of a GFP-LC3
      construct. The knockdown of ATG5 expression blocked GFP-LC3 vesicularization and
      enhanced cell killing. Thus ceramide-CD95 signaling promoted cell death via
      activation of pro-caspase 8 and cell survival via autophagy. PERK was shown to
      signal in a switch-hitting fashion; PERK promoted CD95-DISC formation and an
      eIF2alpha-dependent reduction in c-FLIP-s levels that were essential for cell
      killing to proceed, but in parallel it also promoted autophagy that was
      protective. The death receptor-induced apoptosis and autophagy occur proximal to
      the receptor rather than the mitochondrion, and the relative flow of death
      receptor signaling into either pathway may determine cell fate. Finally, death
      receptor induced apoptosis and autophagy could be potential targets for
      therapeutic intervention.

PMID- 18719358
TI  - Dissecting autophagosome formation: the missing pieces.
AB  - The formation of autophagosomes is the central part of the macroautophagy
      pathway. Little is known, however, about how the participants in this process
      affect the membrane dynamics at the phagophore assembly site (PAS). Recently, we
      demonstrated that Atg8, a lipid-conjugated ubiquitin-like protein, controls the
      expansion of the phagophore. In addition, we showed that the autophagosome
      formation process can be traced and dissected by time-lapse fluorescence
      microscopy observation of GFP-Atg8. These findings constitute one step further in
      our understanding of autophagosome formation. Key questions remain open, however,
      on how the actions of other proteins at the PAS are coordinated with that of Atg8
      and on the precise role of Atg8.

PMID- 18719359
TI  - In vino, curationis?

PMID- 18719360
TI  - Temporal-mediated FGFR1 independence: implications for targeting candidate
      molecules in prostate cancer.

PMID- 18719361
TI  - FLIP-ping out: death receptor signaling in the prostate.
AB  - Prostate cancer is a leading cause of cancer related death. The growth of normal
      prostate epithelial cells is under the tight control of various growth factors,
      most notably androgens, such that castration leads to apoptosis of this cell
      population. Androgen-depletion has a similar effect on prostate cancers; however,
      following initial regression tumors often return in an androgen-depletion
      independent form that is frequently lethal. Thus, castration induced prostate
      regression in rodents has been a valuable model for identifying cell signaling
      pathways that control the proliferation and apoptosis of both normal and
      neoplastic prostate epithelial cells. For example, studies of normal prostate
      regression demonstrated the critical role of paracrine (stromally produced)
      transforming growth factor-beta. This review examines the role of the TNF-family
      death receptors and caspases-8 and -10 in prostate epithelial cell death. There
      is significant evidence that expression of the caspase-8 inhibitor FLIP (FLICE
      like inhibitory protein) is androgen regulated and that this protein is one of
      the key regulators of androgen withdrawal induced cell death. However, it is not
      yet known which of the death receptor pathways is required for prostate apoptosis
      in vivo, and this remains an active topic of research.

PMID- 18719362
TI  - Mitochondrial control of epigenetics.

PMID- 18719363
TI  - The metastasis-associated gene MTA1 is upregulated in advanced ovarian cancer,
      represses ERbeta, and enhances expression of oncogenic cytokine GRO.
AB  - The metastasis-associated genes MTA1 and MTA3 are transcriptional repressors with
      potential effects on cancer. We analyzed the expression of MTA1, MTA3, ERalpha,
      ERbeta and E-cadherin in a total of 115 paraffin-embedded ovarian cancer tissues
      with respect to cancer staging and FIGO grading. Expression of MTA1, but not that
      of MTA3, was found to be significantly enhanced in ovarian cancer tissues with
      advanced cancer stages and higher FIGO grading, indicating an important role of
      MTA1 in the progression of ovarian cancer. To get further insights into the
      function of MTA1 in ovarian cancer, MTA1-overexpressing cancer cell clones were
      generated. In vitro, overexpression of exogenous MTA1 in OVCAR-3 cells had no
      effect on cell proliferation but enhanced the ability of anchorage-independent
      growth in soft agar colony formation assays. MTA1 overexpression resulted in
      downregulation of E-cadherin and MTA3 expression and enhanced expression of the
      transcriptional repressors SNAIL and SLUG. MTA1 further reduced ERbeta expression
      in vitro and inversely correlated with ERbeta expression in vivo. Screening for
      the expression of angiogenic cytokines expressed by ovarian cancer cells revealed
      MTA1-mediated upregulation of the oncogenic and angiogenic cytokine GRO (growth
      regulated oncogene, CXCL1). Thus, in ovarian cancer, MTA1 expression directly and
      indirectly regulates the expression of several cancer-promoting as well as
      metastasis-facilitating factors, indicating an important role for MTA1 expression
      during ovarian cancer progression.

PMID- 18719364
TI  - Gene delivery by embryonic stem cells for malignant glioma therapy: hype or hope?
AB  - Patients with glioblastomas have a poor prognosis and new treatments paradigms
      are needed. The futility of current treatments lies in part on the difficulty of
      delivering therapeutic agents to the tumor. In this article, we review and
      discuss current knowledge of adjuvant treatment for glioblastomas including gene
      therapy and viral vectors. Additionally, this review provides an update on recent
      progress, which has focused on improving delivery methods including the
      development of new approaches such as stem cells. Particular emphasis is given to
      laboratory data showing the use of embryonic stem cells used as vectors to
      deliver pro-apoptotic genes to glioblastoma cells.

PMID- 18719365
TI  - Platinums sensitize human epithelial tumor cells to lymphotoxin alpha by
      inhibiting NFkappaB-dependent transcription.
AB  - Lymphotoxin alpha (LTalpha) was first identified as a direct anti-tumor factor,
      whereas increasing evidence has recently shown that in most cases the growth
      inhibition mediated by LTalpha requires the synergistic action of other factors,
      such as RNA transcription or protein synthesis inhibitor. In this study, we
      evaluated the combined effects of LTalpha and ten chemotherapeutic drugs on cell
      growth in a panel of human epithelial tumor cells, and explored the molecular
      mechanism of their mutual action. The results showed that platinums (cisplatin,
      carboplatin, oxaliplatin) are more universally effective than other
      chemotherapeutic drugs (doxorubicin, epi-doxorubicin, 5-flourouracil, mitomycin,
      cyclophosphamide, vincristine and vinorelbine) to enhance the response of six
      human epithelial tumor cell lines (A375, Bcap37, NCI-H157, SW480, BGC-823 and
      HeLa) to LTalpha. A systemic treatment with a combination of LTalpha and
      cisplatin in a human Bcap37 breast cancer xenograft nude mice model dramatically
      improved the therapeutic efficacy of LTalpha. Further analysis revealed that the
      sensitization of platinums was associated with platinums-induced suppression of
      nuclear factor-kappaB (NFkappaB) and subsequent downregulation of X-linked
      inhibitor of apoptosis protein (XIAP), which rescued caspase-3 from inhibition.
      Our results suggested that a proper combination of bio-agents such as LTalpha and
      conventional chemotherapeutic drugs such as platinums may be an efficient
      treatment strategy for human epithelial cancers.

PMID- 18719366
TI  - Androgen responsive and refractory prostate cancer cells exhibit distinct
      curcumin regulated transcriptome.
AB  - Curcumin (diferuloylmethane) is the major active component of turmeric and is
      being actively investigated for its anti-cancer properties. To better understand
      the biological mechanisms of the chemopreventive potential of curcumin in
      prostate cancer, we have evaluated curcumin regulated transcriptome in prostate
      cancer cells. Hierarchical clustering methods and functional classification of
      the Curcumin-Gene Expression Response (Cu-GER) showed temporal co-regulation of
      genes involved in oxidative stress response and growth signaling pathways.
      Interestingly, C4-2B, androgen independent metastatic prostate cancer cells
      exhibited attenuated Cu-GER response in comparison to parental androgen dependent
      and less aggressive LNCaP cells. Androgen Receptor (AR) regulated genes which
      play critical roles in normal growth and differentiation of the prostate gland,
      as well as in prostate cancer, were also a part of the Cu-GER. Of note, curcumin
      downregulated transcript encoded by the potentially causal TMPRSS2-ERG gene
      fusion, a common oncogenic alteration noted in 50-70% of prostate cancer
      patients. Further more, expression of EGFR and ERBB2 receptor were found to be
      downregulated in curcumin treated LNCaP and C4-2B cells. This report for the
      first time establishes novel features of Cu-GER in prostate cancer cells of
      varying tumorigenic phenotypes and provides potentially novel read-outs for
      assessing effectiveness of curcumin in prostate cancer and likely in other
      cancers. Importantly, new gene-networks identified here further delineate
      molecular mechanism(s) of action of curcumin in prostate cancer cells.

PMID- 18719367
TI  - Downregulation of KSR1 in pancreatic cancer xenografts by antisense
      oligonucleotide correlates with tumor drug uptake.
AB  - While antisense oligonucleotide (AS-ODN) technology holds promise for the
      treatment of cancer, to date there have been no clinical successes.
      Unfortunately, current assays are not sufficiently sensitive to measure tissue
      ODN levels. Hence it has not been possible to ascertain whether treatment
      failures result from failure of drug delivery. To investigate the relationship
      between drug uptake and therapeutic effect, we developed an ultrasensitive
      noncompetitive hybridization-ligation enzyme-linked immunosorbent assay (NCHL
      ELISA) to quantify Kinase Suppressor of Ras1 (KSR1) AS-ODN drug uptake in plasma
      and tumor tissues. In mice harboring PANC-1 pancreatic cancer xenografts and
      continuously infused with AS-ODN, our ELISA detects plasma and tumor KSR1 AS-ODN
      levels over an extended range, from 0.05 nM to 20 nM. Using this sensitive assay,
      we demonstrate that KSR1 repression in pancreatic cancer xenografts correlates
      highly with AS-ODN uptake into tumor tissues. In contrast, plasma drug levels do
      not correlate with tumor drug content or target downregulation. These studies
      indicate the efficacy of our ELISA, and suggest that tumor biopsy material will
      need to be procured to estimate the potential of this antisense technology.

PMID- 18719368
TI  - Hearts lacking caveolin-1 develop hypertrophy with normal cardiac substrate
      metabolism.
AB  - Long-chain fatty acids (FA) are the primary energy source utilized by the adult
      heart. However, during pathological cardiac hypertrophy the fetal gene program is
      reactivated and glucose becomes the major fuel source metabolized by the heart.
      Herein we describe the metabolic phenotype associated with caveolin-1(Cav1) gene
      ablation (Cav1ko) in cardiac fibroblasts. Cav1, the primary protein component of
      caveolae in non-muscle cells co-localizes with a number of proteins involved in
      substrate metabolism, including, FA translocase (CD36) and the insulin receptor.
      We demonstrate that Cav1ko hearts develop cardiac hypertrophy and contractile
      dysfunction at 5-6mos of age. Surprisingly, we observed an increase in the uptake
      of Intralipid triglyceride and albumin bound FA by 25% and 47%, respectively, in
      Cav1ko hearts. Isolated perfused heart studies revealed no significant difference
      in glucose oxidation and glycolysis, however, we observed a trend toward
      increased FA oxidation in Cav1ko hearts. Real-time PCR analysis revealed no
      significant changes in the expression of genes involved in FA and glucose
      metabolism. We also report myocardial triglyceride, fatty acid and cholesterol
      levels are significantly reduced in Cav1ko hearts. Microarray gene expression
      analysis revealed changes in genes that regulate calcium ion and lipid transport
      as well as a number of genes not previously linked to cardiac hypertrophy. We
      observed a 4-fold increase in tetraspanin-2 gene expression, a transmembrane
      protein implicated in regulating intracellular trafficking. Oxysterol binding
      protein related protein-3, which has been implicated in intracellular lipid
      synthesis and transport, was increased 3.6-fold. In addition, sarcoplasmic
      reticulum Ca(2+)-ATPase 3, and calcyclin gene transcripts were significantly
      increased in Cav1ko hearts. In summary, targeted loss of Cav1 produces a unique
      model of cardiac hypertrophy with normal substrate utilization and expression of
      genes involved in energy metabolism.

PMID- 18719369
TI  - An SNP-guided microRNA map of fifteen common human disorders identifies a
      consensus disease phenocode aiming at principal components of the nuclear import
      pathway.
AB  - Recent large-scale genome-wide association (GWA) studies of SNP variations
      captured many thousands individual genetic profiles of H. sapiens and facilitated
      identification of significant genetic traits which are highly likely to influence
      the pathogenesis of several major human diseases. Here we apply the integrative
      genomics principles to interrogate relationships between structural features and
      gene expression patterns of disease-linked SNPs, microRNAs and mRNAs of protein
      coding genes in association to phenotypes of 15 major human disorders, namely
      bipolar disease (BD); rheumatoid arthritis (RA); coronary artery disease (CAD);
      Crohn's disease (CD); type 1 diabetes (T1D); type 2 diabetes (T2D); hypertension
      (HT); ankylosing spondylitis (AS); Graves' disease (autoimmune thyroid disease;
      AITD); multiple sclerosis (MS); breast cancer (BC); prostate cancer (PC);
      systemic lupus erythematosus (SLE); vitiligo-associated multiple autoimmune
      disease (VIT); and ulcerative colitis (UC). We selected for sequence homology
      profiling a set of approximately 250 SNPs which were unequivocally associated
      with common human disorders based on multiple independent studies of 220,124
      individual samples comprising 85,077 disease cases and 129,506 controls. Our
      analysis reveals a systematic primary sequence homology/complementarity-driven
      pattern of associations between disease-linked SNPs, microRNAs and protein-coding
      mRNAs defined here as a human disease phenocode. We utilize this approach to draw
      SNP-guided microRNA maps of major human diseases and define a consensus disease
      phenocode for fifteen major human disorders. A consensus disease phenocode
      comprises 72 SNPs and 18 microRNAs with an apparent propensity to target mRNA
      sequences derived from a single protein-coding gene, KPNA1. Each of microRNAs in
      this elite set appears linked to at least three common human diseases and has
      potential protein-coding mRNA targets among the principal components of the
      nuclear import pathway. We confirmed the validity of our findings by analyzing
      independent sets of most significant disease-linked SNPs and demonstrating
      statistically significant KPNA1-gene expression phenotypes associated with human
      genotypes of CD, BD, T2D and RA populations. Our analysis supports the idea that
      variations in DNA sequences associated with multiple human diseases may affect
      phenotypes in trans via non-protein-coding RNA intermediaries interfering with
      functions of microRNAs and defines the nuclear import pathway as a potential
      major target in 15 common human disorders.

PMID- 18719370
TI  - A role for Drosophila Polo protein in chromosome resolution and segregation
      during mitosis.
AB  - Correct chromosome structure is essential to ensure faithful segregation during
      mitosis. Chromosome condensation occurs at the same time as cohesion is released
      from the arms of the sister chromatids. It is not until metaphase-anaphase
      transition that chromosomes lose cohesion completely, by proteolysis of the
      component of the cohesin complex Scc1 (Sister chromatid cohesion 1). It has been
      shown in vertebrates that the Polo-like kinase, Plk1, is important for this
      process by inducing the destabilization of Scc1 from the chromosome arms. It is
      still unclear if this process is conserved in other high eukaryotes, namely in
      Drosophila. Here we analysed the consequences over chromosome resolution of the
      downregulation of Drosophila Polo, both by mutant analysis and by RNAi-depletion
      in S2 cells. We show that the depletion of Polo results in a strong
      prometa/metaphase arrest with the spindle checkpoint activated in response to
      lack of tension. In addition, the checkpoint protein ROD fails to stream over the
      kinetochore microtubules in the lack of Polo activity. We also show that loss of
      Polo causes strong defects in chromosome resolution, a phenotype we partially
      rescued by depleting Scc1. Importantly, we show Scc1 fails to accumulate on the
      kinetochores during mitosis and remains on the chromosome arms in the absence of
      Polo. We therefore propose an alternative role for Drosophila Polo in Scc1
      redistribution during mitosis.

PMID- 18719371
TI  - p53-Ubl fusions as models of ubiquitination, sumoylation and neddylation of p53.
AB  - The tumour suppressor p53 has been shown to be modified at its C-terminus with
      ubiquitin and the ubiquitin-like proteins SUMO and NEDD8. Whereas
      monoubiquitination of p53 is strongly associated with nuclear export, the effects
      of sumoylation and neddylation remain unclear. In this study we have generated
      p53-Ub, p53-SUMO-1 and p53-NEDD8 fusion proteins as models for the effect of
      these modifications on the localization and function of p53. As shown before, the
      ubiquitin fusion clearly drives nuclear export of p53 and we now find that this
      is also partially the case for a SUMO-1 fusion, which does not localise to PML
      bodies. In contrast a NEDD8 fusion has little effect on nuclear export, and
      mutating NEDD8 to more closely resemble ubiquitin did not restore nuclear export.
      Despite their differing subcellular localization, we find that both p53-ubiquitin
      and p53-NEDD8 retain similar transcriptional activity and both induce apoptosis
      at a similar level to unfused p53. The p53-ubiquitin fusion protein is
      potentially a good model for studying the role of p53 outside the nucleus.
      However, in our experiments we find that the export of p53 from the nucleus is
      not sufficient to activate its cytoplasmic apoptotic function which may depend on
      the ability to deubiquitinate cytoplasmic p53.

PMID- 18719372
TI  - Mechanistic principles of chromatin remodeling guided by siRNAs and miRNAs.
AB  - Small RNAs can guide chromatin remodeling in mammalian cells, but the mechanisms
      involved are poorly understood. Previous reports have shown a requirement for
      overlapping transcription and the involvement of Argonaute (Ago) proteins. Here,
      we use the Regulatory Domain (RD) of the INK4/ARF locus as an experimental
      platform susceptible to siRNA-guided chromatin remodeling to interrogate about
      the mechanisms involved. We show that siRNA-guided chromatin remodeling of RD
      requires overlapping transcription, and targets the transcribed strand, but not
      the template strand, supporting an RNA:RNA recognition mechanism between the
      small RNA and the nascent RNA transcript. We found that heterochromatin formation
      can be triggered both by perfectly-matched double-stranded RNA precursors, as
      well as, by imperfectly-matched double-stranded RNA precursors. These
      observations, together with the fact that promoters are often subjected to
      overlapping transcription, open the possibility that miRNAs could also be able to
      guide heterochromatin formation at promoters. We demonstrate this possibility
      showing that miRNAs miR17-5p and miR20a from the oncomiR cluster miR-17-92 can
      induce heterochromatic features in promoters that undergo overlapping
      transcription and possess sequence complementarity to the miRNA seed region.
      These results unveil a new level of gene regulation by miRNAs.

PMID- 18719373
TI  - Autocrine regulation of glioblastoma cell cycle progression, viability and
      radioresistance through the VEGF-VEGFR2 (KDR) interplay.
AB  - Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis
      and progression of malignant brain tumors. Given the significance of tumor
      microenvironment in general, and the established role of paracrine VEGF signaling
      in glioblastoma (GBM) biology in particular, we explored the potential autocrine
      control of human astrocytoma behavior by VEGF. Using a range of cell and
      molecular biology approaches to study a panel of astrocytoma (grade III and
      IV/GBM)-derived cell lines and a series of clinical specimens from low- and high
      grade astrocytomas, we show that co-expression of VEGF and VEGF receptors
      (VEGFRs) occurs commonly in astrocytoma cells. We found VEGF secretion and VEGF
      induced biological effects (modulation of cell cycle progression and enhanced
      viability of glioblastoma cells) to function in an autocrine manner. Morevover,
      we demonstrated that the autocrine VEGF signaling is mediated via VEGFR2 (KDR),
      and involves co-activation of the c-Raf/MAPK, PI3K/Akt and PLC/PKC pathways.
      Blockade of VEGFR2 by the selective inhibitor (SU1498) abrogated the VEGF
      mediated enhancement of astrocytoma cell growth and viability under unperturbed
      culture conditions. In addition, such interference with VEGF-VEGFR2 signaling
      potentiated the ionizing radiation-induced tumor cell death. In clinical
      specimens, both VEGFRs and VEGF were co-expressed in astroglial tumor cells, and
      higher VEGF expression correlated with tumor progression, thereby supporting the
      relevance of functional VEGF-VEGFR signaling in vivo. Overall, our results are
      consistent with a potential autocrine role of the VEGF-VEGFR2 (KDR) interplay as
      a factor contributing to malignant astrocytoma growth and radioresistance,
      thereby supporting the candidacy of this signaling cascade as a therapeutic
      target, possibly in combination with radiotherapy.

PMID- 18719374
TI  - GFP reporter mice for the retinoblastoma-related cell cycle regulator p107.
AB  - The RB tumor suppressor gene is mutated in a broad range of human cancers,
      including pediatric retinoblastoma. Strikingly, however, Rb mutant mice develop
      tumors of the pituitary and thyroid glands, but not retinoblastoma. Mouse
      genetics experiments have demonstrated that p107, a protein related to pRB, is
      capable of preventing retinoblastoma, but not pituitary tumors, in Rb-deficient
      mice. Evidence suggests that the basis for this compensatory function of p107 is
      increased transcription of the p107 gene in response to Rb inactivation. To begin
      to address the context-dependency of this compensatory role of p107 and to follow
      p107 expression in vivo, we have generated transgenic mice carrying an enhanced
      GFP (eGFP) reporter inserted into a bacterial artificial chromosome (BAC)
      containing the mouse p107 gene. Expression of the eGFP transgene parallels that
      of p107 in these transgenic mice and identifies cells with a broad range of
      expression level for p107, even within particular organs or tissues. We also show
      that loss of Rb results in the upregulation of p107 transcription in specific
      cell populations in vivo, including subpopulations of hematopoietic cells. Thus,
      p107 BAC-eGFP transgenic mice serve as a useful tool to identify distinct cell
      types in which p107 is expressed and may have key functions in vivo, and to
      characterize changes in cellular networks accompanying Rb deficiency.

PMID- 18719375
TI  - Cell death specification in C. elegans.
AB  - Years of research have identified a highly conserved mechanism required for
      apoptotic cell killing. How certain cells are specified to die is not well
      understood. With a rich history in programmed cell death research, the nematode
      C. elegans offers an excellent animal model with which to study cell death
      specification events. Developing hermaphrodites have 131 invariant cell death
      events that can be studied with single cell resolution. Recent genetic studies
      have begun to identify diverse sets of factors required for the proper
      specification of individual cell death events. The limited findings thus far
      suggest that cell death specification is controlled through transcriptional
      regulation of at least two members of the core cell death pathway, egl-1 and ced
      3. However, it remains unclear if additional modes of cell death specification
      exist. Here we briefly summarize current findings in the field of C. elegans cell
      death specification and consider those questions that remain to be answered.

PMID- 18719376
TI  - p53 Binding to the p21 promoter is dependent on the nature of DNA damage.
AB  - p53 Is a tumor suppressor that integrates signals from different stress induced
      signalling pathways, regulates cell cycle arrest, senescence, apoptosis and DNA
      repair. How p53 dictates cell fate is unclear. As a major transcriptional target
      of p53 in response to cellular stress, p21 is a key component in cell cycle
      control and apoptosis, directing an anti-apoptotic response following DNA damage.
      It is therefore likely that p53-dependent regulation of p21 contributes, at least
      in part, how p53 influences cellular outcome upon DNA damage. Here we compare the
      p53-dependent transcriptional regulation of p21 in response to DNA damage by
      ultraviolet (UV) radiation and ionizing radiation (IR). We demonstrate that
      despite comparable levels of p53 accumulation by both types of DNA damage, IR
      causes significant, early accumulation of p21 not seen in UV-damaged cells, with
      a substantially different cell cycle profile. Whereas UV and IR both target p21
      protein for degradation immediately after DNA damage, differential post-damage
      p21 transcription is accountable for the disparity in p21 protein levels.
      Chromatin immunoprecipitation studies reveal that p53 displays a clear bias
      against the p21 promoter in UV-damaged cells compared to IR-damaged cells. We
      note differential post-translational modifications of nuclear p53 between UV and
      IR treatment. Furthermore we demonstrate that this disparity correlated with
      reduced histone acetylation on the TATA box within the p21 promoter following UV
      treatment. This suggests that the nature of DNA damage enables p53 to selectively
      discriminate between promoters in the induction of target genes, thereby
      regulating their expression and subsequent cellular outcome.

PMID- 18719377
TI  - Targeting the eIF4F translation initiation complex for cancer therapy.
AB  - In multiple human cancers, the function of the eukaryotic translation initiation
      factor 4E (eIF4E) is elevated and directly related to disease progression.
      Overexpression or hyperactivation of eIF4E in experimental models can drive
      cellular transformation and malignant progression. Elevated eIF4E function
      triggers enhanced assembly of the eIF4F translation initiation complex and
      thereby drives cap-dependent translation. Though all capped mRNAs require eIF4F
      for translation, a pool of mRNAs are exceptionally dependent on elevated eIF4F
      activity for translation and are thereby selectively and disproportionately
      affected by altered eIF4F activity. These mRNAs encode proteins that play
      significant roles in all aspects of malignancy including angiogenesis factors
      (VEGF, FGF-2), onco-proteins (c-myc, cyclin D1, ODC), pro-survival proteins
      (survivin, BCL-2) and proteins involved in tumor invasion and metastasis (MMP-9,
      heparanase). Recent advances in targeting the eIF4F complex have highlighted the
      role for this complex in tumor cell survival and angiogenesis and have
      illuminated the enhanced susceptibility of the tumor cells to inhibition of the
      eIF4F complex. These studies have demonstrated the attractiveness and
      plausibility of targeting eIF4E and the eIF4F translation initiation complex for
      cancer therapy and have prompted the advance of the first eIF4E-specific therapy
      to the clinic.

PMID- 18719378
TI  - Functional integration of microRNAs into oncogenic and tumor suppressor pathways.
AB  - A large body of evidence has documented abnormal microRNA (miRNA) expression
      patterns in diverse human malignancies. Given that miRNA expression is tightly
      regulated during development and cellular differentiation, aberrant miRNA
      expression in cancer cells is likely to be in part a consequence of the loss of
      normal cellular identity that accompanies malignant transformation. Nevertheless,
      it is now clear that miRNAs function as critical effectors of several canonical
      oncogenic and tumor suppressor pathways, including those controlled by Myc and
      p53. Gain- and loss-of-function of these factors in cancer cells contributes to
      miRNA dysregulation, directly influencing neoplastic phenotypes including
      cellular proliferation and apoptosis.

PMID- 18719379
TI  - Mechanotransduction and anoikis: death and the homeless cell.
AB  - Developed organs display strict spatial organization of differentiated cells
      which is required for proper organ function. One important device that prevents
      tissue disorganization is the death of cells that lose anchorage to their native
      matrix, a signal that indicates potential loss of proper tissue context. Termed
      anoikis (Greek for Homelessness), this form of cell death is a specialized form
      of apoptosis. Interestingly, at certain stages of development and tissue repair,
      cells are required to migrate in an unanchored state, suggesting that anoikis
      must be strictly regulated at some level. Likewise, cellular transformation is
      often accompanied by an inappropriate loss of anoikis and subsequent acquisition
      of a metastatic phenotype. Despite its importance, the molecular pathways
      involved in the regulation of anoikis and the proximal signals reporting loss of
      anchorage are poorly understood. Recent studies suggest that attachment may be
      reported by a mechanosensory testing of the cell's physical environment.

PMID- 18719380
TI  - microRNAs and cancer: an overview.
AB  - MicroRNAs (miRNAs) are a recently discovered class of small RNA molecules that
      negatively regulate gene expression at the post-transcriptional level. MiRNAs
      play key roles in development and establishment of cell identity and aberrant
      metabolism/expression of miRNAs has been linked to human diseases including
      cancer. Components of the miRNA machinery and miRNAs themselves are involved in
      many cellular processes that are altered in cancer, such as differentiation,
      proliferation and apoptosis. Some miRNAs exhibit differential expression levels
      in cancer and have demonstrated capability to affect cellular transformation,
      carcinogenesis and metastasis acting either as oncogenes or tumour suppressors.
      We are only beginning to comprehend the functional repercussions of the gain or
      loss of particular microRNAs on cancer. Nonetheless, although microRNAs have been
      discovered in humans a mere eight years ago, a host of promising potential
      applications in the diagnosis, prognoses and therapy of cancer are emerging at a
      rapid pace.

PMID- 18719381
TI  - Remarkable features of tiny RNA molecules: highlights of revolutionary
      discoveries on the path from the bench to bedside.

PMID- 18719382
TI  - Modulation of the "blood-tumor" barrier improves immunotherapy.
AB  - Blood vessels inside tumors are crucial for cancer survival and progression but
      equally contribute to the tumor's intrinsic resistance to therapy. Abnormal blood
      flow in the local tumor environment acts as a physiological barrier to the
      delivery of chemotherapeutic agents. Furthermore, tumor vasculature can also act
      as a barrier for immune cell migration into the tumor parenchyma. Much has been
      made of anti-angiogenic therapies that specifically inhibit vessel growth.
      However, recent findings demonstrate that the chaotic architecture of tumor blood
      vessels can be reversed which in turn normalizes blood flow and physical
      parameters in the tumor environment. Importantly, vessel normalization also
      improves lymphocyte migration into tumor tissue and immune destruction.
      Identification of regulator of G protein signaling 5 (RGS5) as a key modulator of
      the vascular barrier in tumor progression and regression has brought new insights
      into the molecular basis of vessel normalization and opens new therapeutic
      opportunities.

PMID- 18719383
TI  - Mitochondrially targeted wild-type p53 induces apoptosis in a solid human tumor
      xenograft model.
AB  - Classic but also novel roles of p53 are becoming increasingly well characterized.
      We previously showed that ex vivo retroviral transfer of mitochondrially targeted
      wild type p53 (mitop53) in the Emu-myc mouse lymphoma model efficiently induces
      tumor cell killing in vivo. In an effort to further explore the therapeutic
      potential of mitop53 for its pro-apoptotic effect in solid tumors, we generated
      replication-deficient recombinant human Adenovirus type 5 vectors. We show here
      that adenoviral delivery of mitop53 by intratumoral injection into HCT116 human
      colon carcinoma xenograft tumors in nude mice is surprisingly effective,
      resulting in tumor cell death of comparable potency to conventional p53. These
      apoptotic effects in vivo were confirmed by Ad5-mitop53 mediated cell death of
      HCT116 cells in culture. Together, these data provide encouragement to further
      explore the potential for novel mitop53 proteins in cancer therapy to execute the
      shortest known circuitry of p53 death signaling.

PMID- 18719384
TI  - Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer.
AB  - Recently, we and others identified the microRNA miR-34a as a target of the tumor
      suppressor gene product p53. Ectopic miR-34a induces a G(1) cell cycle arrest,
      senescence and apoptosis. Here we report that miR-34a expression is silenced in
      several types of cancer due to aberrant CpG methylation of its promoter. 19 out
      of 24 (79.1%) primary prostate carcinomas displayed CpG methylation of the miR
      34a promoter and concomitant loss of miR-34a expression. CpG methylation of the
      miR-34a promoter was also detected in breast (6/24; 25%), lung (7/24; 29.1%),
      colon (3/23; 13%), kidney (3/14; 21.4%), bladder (2/6; 33.3%) and pancreatic
      (3/19; 15.7%) carcinoma cell lines, as well as in melanoma cell lines (19/44;
      43.2%) and primary melanoma (20/32 samples; 62.5%). Silencing of miR-34a was
      dominant over its transactivation by p53 after DNA damage. Re-expression of miR
      34a in prostate and pancreas carcinoma cell lines induced senescence and cell
      cycle arrest at least in part by targeting CDK6. These results show that miR-34a
      represents a tumor suppressor gene which is inactivated by CpG methylation and
      subsequent transcriptional silencing in a broad range of tumors.

PMID- 18719386
TI  - microRNA(interference) networks are embedded in the gene regulatory networks.
AB  - microRNAs (miRNAs) are a class of endogenous 22-25 nt single-stranded RNA
      molecules that regulate gene expression post-transcriptionally. They are highly
      conserved among species with distinct temporal and spatial patterns of
      expression, each of them potentially interacting with hundreds of messenger RNAs.
      Since miRNAs, like transcription factors (TFs), are trans-acting factors that
      interact with cis-regulatory elements, they potentially generate a complex
      combinatorial code. Moreover, as TFs and genes containing binding sites for TFs
      have a high probability of being targeted by miRNAs, the basic interplay miRNA/TF
      renders miRNAs key components of gene regulatory networks. Several biological
      processes, including diseases such as cancer, have been causatively associated to
      disturbances of miRNAs/TF interplay both in vitro and in vivo. These aspects,
      cumulatively, indicate that miRNAs and transcription factors have a crucial role
      in determining cellular behaviour, highlighting the role of small RNA molecules
      in regulatory mechanisms and indicating other routes in the evolutionary path of
      gene expression.

PMID- 18719385
TI  - Insights into RNA/DNA hybrid recognition and processing by RNase H from the
      crystal structure of a non-specific enzyme-dsDNA complex.
AB  - Ribonuclease HI (RNase H) is a member of the nucleotidyl-transferase superfamily
      and endo-nucleolytically cleaves the RNA portion in RNA/DNA hybrids and removes
      RNA primers from Okazaki fragments. The enzyme also binds RNA and DNA duplexes
      but is unable to cleave either. Three-dimensional structures of bacterial and
      human RNase H catalytic domains bound to RNA/DNA hybrids have revealed the basis
      for substrate recognition and the mechanism of cleavage. In order to visualize
      the enzyme's interactions with duplex DNA and to establish the structural
      differences that afford tighter binding to RNA/DNA hybrids relative to dsDNA, we
      have determined the crystal structure of Bacillus halodurans RNase H in complex
      with the B-form DNA duplex [d(CGCGAATTCGCG)](2). The structure demonstrates that
      the inability of the enzyme to cleave DNA is due to the deviating curvature of
      the DNA strand relative to the substrate RNA strand and the absence of Mg(2+) at
      the active site. A subset of amino acids engaged in contacts to RNA 2'-hydroxyl
      groups in the substrate complex instead bind to bridging or non-bridging
      phosphodiester oxygens in the complex with dsDNA. Qualitative comparison of the
      enzyme's interactions with the substrate and inhibitor duplexes is consistent
      with the reduced binding affinity for the latter and sheds light on determinants
      of RNase H binding and cleavage specificity.

PMID- 18719387
TI  - RecQ family helicases in genome stability: lessons from gene disruption studies
      in DT40 cells.
AB  - Cells of all living organisms have evolved complex mechanisms to maintain genome
      stability. There is increasing evidence that spontaneous genomic instability
      occurs primarily during DNA replication. RecQ DNA helicases function during DNA
      replication and are essential for the maintenance of genome stability. In human
      cells, there exist five RecQ DNA helicases, and mutations of three of these
      helicases, encoded by the BLM, WRN and RECQL4 genes, give rise to the cancer
      predisposition disorders, Bloom syndrome (BS), Werner syndrome (WS) and Rothmund
      Thomson syndrome (RTS), respectively. Individuals suffering from WS and RTS also
      show premature aging phenotypes. Although the two remaining helicases, RECQL1 and
      RECQL5, have not yet been associated with heritable human diseases, a single
      nucleotide polymorphism of RECQL1 is associated with reduced survival of
      pancreatic cancer, and RecQl5 knockout mice show a predisposition to cancer.
      Here, we review the functions of eukaryotic RecQ helicases, focusing primarily on
      BLM in the maintenance of genome stability through various pathways of nucleic
      acid metabolism and with special reference to DNA replication.

PMID- 18719388
TI  - Lessons from microRNA mutants in worms, flies and mice.
AB  - It is apparent that microRNAs (miRNAs) are important components in the regulation
      of genetic networks in many biological contexts. Based on computational analysis,
      typical miRNAs are inferred to have tens to hundreds of conserved targets. Many
      miRNA-target interactions have been validated by various means, including
      heterologous tests in cultured cells and gain-of-function approaches that can
      yield striking phenotypes in whole animals. However, these strategies do not
      report on the endogenous importance of such miRNA activities. Likewise, studies
      of miRNA pathway mutants can suggest an endogenous role for miRNAs in a given
      setting, but do not identify roles for specific miRNAs. Therefore, these
      approaches must be complemented with the analysis of miRNA mutant alleles. In
      this review, we describe some of the lessons learned from studying miRNA gene
      deletions in worms, flies and mice, and discuss their implications for the
      control of endogenous regulatory networks.

PMID- 18719389
TI  - Strap: a versatile transcription co-factor.
AB  - The Stress-responsive activator of p300 (Strap) is a transcription co-factor that
      has an important role in the control of DNA damage response through its ability
      to regulate p53 activity. Recent studies have however suggested that Strap takes
      on a wider role in regulating the cellular response to stress. Thus, Strap is now
      known to be inducible by heat shock and stimulate the transcription of heat-shock
      genes. A chromatin-associated complex involving heat-shock factor 1 (HSF1), Strap
      and the p300 co-activator assembles on the HSP70 gene promoter, and Strap
      augments HSF1 binding and chromatin acetylation in HSP genes, most probably
      through recruiting p300 acetyltransferase. Cells depleted of Strap do not survive
      under heat-shock conditions. It appears therefore that Strap is an essential co
      factor that acts at the level of chromatin control to regulate heat-shock
      responsive transcription. These recent studies underscore the central role taken
      on by transcription co-factors in integrating and co-ordinating different
      cellular stress response pathways.

PMID- 18719390
TI  - Cancer and aging: more puzzles, more promises?
AB  - In this issue of Cell Cycle, a new paper shows that metformin, an oral
      antidiabetic drug that activates AMP-activated protein kinase, prolongs both mean
      and maximal life span and prevents reproductive aging of female mice.
      Unexpectedly, metformin did not decrease the incidence of cancer in this mice
      strain. Here, we discuss the relationship between aging and cancer, the mechanism
      of metformin action, and the prospects of using this compound for life span
      extension in humans.

PMID- 18719391
TI  - Mechanisms of microRNA deregulation in human cancer.
AB  - microRNAs (miRNAs) are an abundant class of small non-coding RNAs that function
      as gene regulators. Although deregulation of miRNA expression is involved in the
      initiation and progression of tumorigenesis, the underlying mechanisms of miRNA
      deregulation in human cancer are still largely unknown. Increasing evidence
      indicates that transcriptional deregulations, epigenetic alterations, mutations,
      DNA copy number abnormalities and defects in the miRNA biogenesis machinery might
      contribute to miRNA deregulation in human cancer. A clearer understanding of the
      mechanisms involved in miRNA deregulation in human cancer will contribute greatly
      to the development of new miRNA-based strategies in cancer diagnosis and
      treatment.

PMID- 18719392
TI  - Involvement of the p53 and p73 transcription factors in neuroAIDS.
AB  - HIV-associated dementia (HAD) is the most common AIDS-associated neurological
      disorder and is characterized by the development of synaptodendritic injury to
      neurons. To advance HAD therapy, it is crucial to identify the mechanisms and
      factors involved. The viral protein HIV-1 Tat is among those factors and is
      released by HIV-1-infected cells and can be taken up by adjacent neuronal cells
      leading to neurotoxic effects. Multiple cellular host proteins have been
      identified as Tat cofactors in causing neuronal injury. Interestingly, most of
      these factors function through activation of the p53 pathway. We have now
      examined the ability of Tat to activate the p53 pathway leading to the induction
      of endogenous p53 and p73 in neuronal cells. We found that Tat induced p53 and
      p73 levels in SH-SY5Y cells and that this induction caused retraction of
      neurites. In the absence of either p53 or p73, Tat failed to induce dendritic
      retraction or to activate the proapoptotic proteins, such as Bax. Further, we
      found that p53-accumulation in Tat-treated cells depends on the presence of p73.
      Therefore, we conclude that Tat contributes to neuronal degeneration through
      activation of a pathway involving p53 and p73. This information will be valuable
      for the development of therapeutic agents that affect these pathways to protect
      CNS neurons and prevent HAD.

PMID- 18719394
TI  - D2 dopamine receptors interact directly with N-type calcium channels and regulate
      channel surface expression levels.
AB  - N-type channels are located on dendrites and at pre-synaptic nerve terminals
      where they play a fundamental role in neurotransmitter release. They are potently
      regulated by the activation of a number of different types of pertussis toxin
      (PTX)-sensitive G alpha(i/o) coupled receptors, which results in voltage
      dependent inhibition of channel activity via G betagamma subunits. Using
      heterologous expression in HEK 293T cells, we show via whole cell patch clamp
      recordings that D2 receptors mediate both G betagamma (i.e., voltage-dependent)
      and voltage-independent inhibition of channel activity. Furthermore, using co
      immunoprecipitation and pull down assays involving the intracellular regions of
      each protein, we show that D2 receptors and N-type channels form physical
      signaling complexes. Finally, we use confocal microscopy to demonstrate that D2
      receptors regulate N-type channel trafficking to affect the number of calcium
      channels available at the plasma membrane. Taken together, these data provide
      evidence for multiple voltage-dependent and voltage-independent mechanisms by
      which D2 receptor subtypes influence N-type channel activity.

PMID- 18719395
TI  - Molecular determinants of sensitivity and conductivity of human TRPM7 to Mg2+ and
      Ca2+.
AB  - It is known that extracellular Mg(2+) and Ca(2+) can permeate TRPM7 and at the
      same time block the permeation by monovalent cations. In the present study, we
      examined the molecular basis for the conductivity and sensitivity of human TRPM7
      to these divalent cations. Extracellular acidification to pH 4.0 markedly reduced
      the blocking effects of Mg(2+) and Ca(2+) on the Cs(+) currents, decreasing their
      binding affinities: their IC(50) values increased 510- and 447-fold,
      respectively. We examined the effects of neutralizing each of four negatively
      charged amino acid residues, Glu-1047, Glu-1052, Asp-1054 and Asp-1059, within
      the putative pore-forming region of human TRPM7. Mutating Glu-1047 to alanine
      (E1047A) resulted in non-functional channels, whereas mutating any of the other
      residues resulted in functionally expressed channels. Cs(+) currents through
      D1054A and E1052A were less sensitive to block by divalent cations; the IC(50)
      values were increased 5.5- and 3.9-fold, respectively, for Mg(2+) and 10.5- and
      6.7-fold, respectively, for Ca(2+). D1059A also had a significant reduction,
      though less marked compared to the reductions seen for D1054A and E1052A, in
      sensitivity to Mg(2+) (1.7-fold) and Ca(2+) (3.9-fold). The D1054A mutation
      largely abolished inward currents conveyed by Mg(2+) and Ca(2+). In the E1052A
      and D1059A mutants, inward Mg(2+) and Ca(2+) currents were sizable but
      significantly diminished. Thus, it is concluded that in human TRPM7, (1) both Asp
      1054 and Glu-1052, which are located near the narrowest portion in the pore's
      selectivity filter, may provide the binding sites for Mg(2+) and Ca(2+), (2) Asp
      1054 is an essential determinant of Mg(2+)and Ca(2+) conductivity, and (3) Glu
      1052 and Asp-1059 facilitate the conduction of divalent cations.

PMID- 18719393
TI  - Musashi1: a stem cell marker no longer in search of a function.
AB  - One of the earliest genes identified with stem and early progenitor cells is the
      RNA-binding protein, Musashi1 (Msi1). Through gene profiling of mammary
      epithelial cells transduced with Msi1, a unique autocrine signaling pathway was
      identified that activates both the Wnt and Notch pathways. This process was
      associated with increased secretion of the growth factor, PLF1 and inhibition of
      the secreted Wnt pathway inhibitor, DKK3. Identification of PLF1 as an effector
      of these pathways in the absence of the DKK3 tumor suppressor provides a new
      avenue for investigating differences between normal and malignant tissues, and
      potentially targeting tumor stem cells.

PMID- 18719396
TI  - A mutually exclusive alternative exon of slo1 codes for a neuronal BK channel
      with altered function.
AB  - Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels are comprised
      of four pore-forming -subunits (Slo1), whose mRNA is alternatively spliced in a
      cell-specific manner. Here we report the first case of a correctly spliced
      mutually exclusive exon in a mammalian (human and mouse) BK channel; an exon
      coding for the region from S6 to the RCK1 domain is exchanged for an alternative
      exon of the same length. The slo1 transcript with this novel exon is present in
      native brain tissues and inclusion of the alternative exon profoundly alters the
      channel's gating characteristics: faster activation at low Ca(2+) concentrations
      and greater open probability at resting membrane potential at high Ca(2+)
      concentrations. The novel gating features conferred by the alternative exon are
      dominant over those of the commonly described Slo1 variant when coexpressed. The
      evolutionarily preserved splicing of the Slo1 S6-RCK1 linker segment possess
      great potential to fine-tune neuronal excitability.

PMID- 18719397
TI  - Exploring the function and pharmacotherapeutic potential of voltage-gated Ca2+
      channels with gene knockout models.

PMID- 18719399
TI  - The elusive Dnmt1 and its role during early development.

PMID- 18719398
TI  - Maize lines expressing RNAi to chromatin remodeling factors are similarly
      hypersensitive to UV-B radiation but exhibit distinct transcriptome responses.
AB  - RNAi knockdown lines targeting two putative chromatin factors (a methyl-CpG
      binding domain protein MBD101 and a chromatin remodeling complex protein CHC101)
      exhibit identical phenotypic consequences after UV-B exposure including necrosis
      in adult leaves and seedling death. Here we report that these RNAi lines exhibit
      substantially different transcriptome changes assessed on a 44 K Agilent
      oligonucleotide array platform compared to each other and to UV-B tolerant non
      transgenic siblings both before and after 8 h of UV-B exposure. Adult maize
      leaves express approximately 26,000 transcript types under greenhouse growth
      conditions; after 8 h of UV-B exposure 267 transcripts exhibit an expression
      change in the B73 control line. Most of these transcript abundance changes in B73
      after UV-B treatment are not found in the two RNAi knockdown lines: 119
      upregulated transcript types and 128 downregulated types are uniquely modulated
      in B73. The mbd101 RNAi line shows many more line-specific transcript changes
      (897 up, 68 down) than either B73 or the chc101 line (72 up, 103 down). By
      functional analysis, the largest category of genes with predicted functions
      affected by UV-B is the DNA/chromatin binding group. Differential activation of
      suites of transcription factors in the control and transgenic lines are the
      likely explanation for the divergent transcriptome profiles.

PMID- 18719400
TI  - Will the transcription control elements in chromatin please stand up?

PMID- 18719401
TI  - Epigenetic integration of environmental and genomic signals in honey bees: the
      critical interplay of nutritional, brain and reproductive networks.
AB  - The discovery of a family of highly conserved DNA cytosine methylases in honey
      bees and other insects suggests that, like mammals, invertebrates possess a
      mechanism for storing epigenetic information that controls heritable states of
      gene expression. Recent data also show that silencing DNA methylation in young
      larvae mimics the effects of nutrition on early developmental processes that
      determine the reproductive fate of honey bee females. We evaluate the impact of
      these findings on future studies of environmentally-driven phenotypic plasticity
      in social insects, and discuss how they may help in understanding the nutritional
      basis of epigenetic reprogramming in humans.

PMID- 18719402
TI  - Conference report for the 2nd MC-GARD series on "Interplay among genetics,
      epigenetics and non-coding RNAs".
AB  - During May 2008, the 2nd Marie-Curie Genome Architecture in Relation to Disease
      Conference (MC-GARD.eu) on "Interplay among genetics, epigenetics and non-coding
      RNAs" took place in Madrid, Spain. The organizers brought together approximately
      120 participants from all over the world to discuss epigenetic mechanisms in
      relation to normal and disease states, with emphasis on diagnosis, prognosis and
      therapeutic interventions.

PMID- 18719404
TI  - Cloning of the neurodegeneration gene drop-dead and characterization of
      additional phenotypes of its mutation.
AB  - Mutations in the Drosophila gene drop-dead (drd) result in early adult lethality
      and neurodegeneration, but the molecular identity of the drd gene and its
      mechanism of action are not known. This paper describes the characterization of a
      new X-linked recessive adult-lethal mutation, originally called lot's wife
      (lwf(1)) but subsequently identified as an allele of drd (drd(lwf)); drd(lwf)
      mutants die within two weeks of eclosion. Through mapping and complementation,
      the drd gene has been identified as CG33968, which encodes a putative integral
      membrane protein of unknown function. The drd(lwf) allele is associated with a
      nonsense mutation that eliminates nearly 80% of the CG33968 gene product;
      mutations in the same gene were also found in two previously described drd
      alleles. Characterization of drd (lwf) flies revealed additional phenotypes of
      drd, most notably, defects in food processing by the digestive system and in
      oogenesis. Mutant flies store significantly more food in their crops and defecate
      less than wild-type flies, suggesting that normal transfer of ingested food from
      the crop into the midgut is dependent upon the DRD gene product. The defect in
      oogenesis results in the sterility of homozygous mutant females and is associated
      with a reduction in the number of vitellogenic egg chambers. The disruption in
      vitellogenesis is far more severe than that seen in starved flies and so is
      unlikely to be a secondary consequence of the digestive phenotype. This study
      demonstrates that mutation of the drd gene CG33968 results in a complex phenotype
      affecting multiple physiological systems within the fly.

PMID- 18719403
TI  - The Drosophila protein palmitoylome: characterizing palmitoyl-thioesterases and
      DHHC palmitoyl-transferases.
AB  - Palmitoylation is the post-translational addition of a palmitate moiety to a
      cysteine residue through a covalent thioester bond. The addition and removal of
      this modification is controlled by both palmitoyl acyl-transferases and
      thioesterases. Using bioinformatic analysis, we identified 22 DHHC family
      palmitoyl acyl-transferase homologs in the Drosophila genome. We used in situ
      hybridization,RT-PCR, and published FlyAtlas microarray data to characterize the
      expression patterns of all 22 fly homologs. Our results indicate that all are
      expressed genes, but several, including CG1407, CG4676, CG5620, CG6017/dHIP14,
      CG6618, CG6627 and CG17257 appear to be enriched in neural tissues suggesting
      that they are important for neural function. Furthermore, we have found that
      several may be expressed in a sex-specific manner with adult male specific
      expression of CG4483 and CG17195. Using tagged versions of the DHHC genes, we
      demonstrate that fly DHHC proteins are primarily located in either the Golgi
      Apparatus or Endoplasmic Reticulum in S2 cells, except for CG1407, which was
      found on the plasma membrane. We also characterized the subcellular localization
      and expression of the three known thioesterases: Palmitoyl-protein Thioesterase 1
      (Ppt1), Palmitoyl-protein Thioesterase 2 (Ppt2)and Acyl-protein Thioesterase 1
      (APT1). Our results indicate that Ppt1 and Ppt2 are the major lysosomal
      thioesterases while APT1 is the likely cytoplasmic thioesterase. Finally, in vivo
      rescue experiments show that Ppt2 expression cannot rescue the neural inclusion
      phenotypes associated with loss of Ppt1, further supporting distinct functions
      and substrates for these two thioesterases. These results will serve as the basis
      for a more complete understanding of the protein palmitoylome's normal cellular
      functions in the fly and will lead to further insights into the molecular
      etiology of diseases associated with the mis-regulation of palmitoylation.

PMID- 18719405
TI  - Tandem affinity purification in Drosophila: the advantages of the GS-TAP system.
AB  - Tandem affinity purification (TAP) has been widely used for the analysis of
      protein complexes. We investigated the parameters of the recently developed TAP
      method (GS-TAP) and its application in Drosophila. This new tag combination
      includes two Protein G modules and a streptavidin binding peptide (SBP),
      separated by one or two TEV protease cleavage sites. We made pMK33-based GS-TAP
      vectors to allow for generation of stable cell lines using hygromycin selection
      and inducible expression from a metallothionein promoter, as well as pUAST-based
      vectors that can be used for inducible expression in flies. Rescue experiments in
      flies demonstrated that the GS-TAP tag preserves the function of the tagged
      protein. We have done parallel purifications of proteins tagged with the new GS
      TAP tag or with the conventional TAP tag (containing the Protein A and calmodulin
      binding peptide domains) at the amino terminus, using both cultured cells and
      embryos. A major difference between the two tags was in the levels of
      contaminating proteins, which were significantly lower in the GS-TAP
      purifications. The GS-TAP procedure also resulted in higher yield of the bait
      protein. Overall, GS-TAP is an improved method of protein complex purification
      because it provides a superior signal-to-noise ratio of the bait protein relative
      to contaminants in purified material.

PMID- 18719406
TI  - Changes in cuticular lipids, water loss and desiccation resistance in a tropical
      drosophilid: analysis of variation between and within populations.
AB  - We investigated within as well as between population variability in desiccation
      resistance, cuticular lipid mass per fly and cuticular water loss in nine
      geographical populations of a tropical drosophilid, Zaprionus indianus.
      Interestingly, the amount of cuticular lipids and desiccation resistance in this
      non-melanic species are significantly higher as compared with melanic Drosophila
      melanogaster. On the basis of isofemale line analysis, within population trait
      variability in cuticular lipid mass per fly is positively correlated with
      desiccation resistance and negatively correlated with cuticular water loss but
      show lack of correlation with body size. We observed geographical variation in
      the amount of cuticular lipid mass per fly in Zaprionus indianus but no such
      divergence was found in D.melanogaster. In both the species, geographical
      variations in desiccation resistance are negatively correlated with cuticular
      water loss but the underlying mechanisms for changes in cuticular permeability
      are quite different. Thus, we may suggest that body melanisation and cuticular
      lipids may represent alternative strategies for coping with dehydration stress in
      melanic versus non-melanic drosophilids. For both the species, desiccation
      resistance and cuticular water loss are correlated with regular increase in
      aridity in the northern subtropical localities as compared with southern
      peninsular humid tropical localities. The role of climatic selection is evident
      from multiple regression analysis with seasonal changes in temperature and
      humidity (Tcv and RHcv) of the sites of origin of populations of Zaprionus
      indianus along latitude.

PMID- 18719407
TI  - Distinct heparan sulfate compositions in wild-type and pipe-mutant eggshell
      matrix.
AB  - Spatial information embedded in the extracellular matrix establishes the
      dorsoventral polarity of the Drosophila embryo through the ventral activity of a
      serine protease cascade. Pipe is a Golgi-localized protein responsible for
      generating this spatial information during oogenesis through sulfation of unknown
      glycans. Although Pipe has sequence homology to glycosaminoglycan 2-O
      sulfotransferases, its activity and authentic substrates have not been
      demonstrated and genetic evidence has argued against a role for
      glycosaminoglycans in dorsoventral polarity establishment. Here, direct
      examination of matrix glycosaminoglycans demonstrates that pipe-mutant matrix
      shows decreased tri-sulfated heparan sulfate compared to wild-type matrix, with
      correspondingly increased 2-O-sulfated heparan sulfate. Chondroitin sulfate was
      not detected in this matrix. These results suggest that Pipe promotes 6-O- and/or
      N-sulfation of heparan sulfate but is not required for heparan sulfate 2-O
      sulfation. We discuss the possible significance of these unexpected findings and
      how they might be reconciled with the genetic data.

PMID- 18719433
TI  - Diabetes mellitus and subclinical neuropathy: a call for new paths in peripheral
      nerve block research.

PMID- 18719434
TI  - Undetected residual neuromuscular block has consequences.

PMID- 18719435
TI  - We care, therefore we are: anesthesia-related morbidity and mortality: the 46th
      Rovenstine Lecture.

PMID- 18719436
TI  - Intraoperative acceleromyographic monitoring reduces the risk of residual
      neuromuscular blockade and adverse respiratory events in the postanesthesia care
      unit.
AB  - BACKGROUND: Incomplete recovery from neuromuscular blockade in the postanesthesia
      care unit (PACU) may contribute to adverse postoperative respiratory events. This
      study determined the incidence and degree of residual neuromuscular blockade in
      patients randomized to conventional qualitative train-of-four (TOF) monitoring or
      quantitative acceleromyographic monitoring. The incidence of adverse respiratory
      events in the PACU was also evaluated. METHODS: One hundred eighty-five patients
      were randomized to intraoperative acceleromyographic monitoring
      (acceleromyography group) or qualitative TOF monitoring (TOF group). Anesthetic
      management was standardized. TOF patients were extubated when standard criteria
      were met and no fade was observed during TOF stimulation. Acceleromyography
      patients had a TOF ratio of greater than 0.80 as an additional extubation
      criterion. Upon arrival in the PACU, TOF ratios of both groups were measured with
      acceleromyography. Adverse respiratory events during transport to the PACU and
      during the first 30 min of PACU admission were also recorded. RESULTS: A lower
      frequency of residual neuromuscular blockade in the PACU (TOF ratio < or = 0.9)
      was observed in the acceleromyography group (4.5%) compared with the conventional
      TOF group (30.0%; P < 0.0001). During transport to the PACU, fewer
      acceleromyography patients developed arterial oxygen saturation values, measured
      by pulse oximetry, of less than 90% (0%) or airway obstruction (0%) compared with
      TOF patients (21.1% and 11.1%, respectively; P < 0.002). The incidence, severity,
      and duration of hypoxemic events during the first 30 min of PACU admission were
      less in the acceleromyography group (all P < 0.0001). CONCLUSIONS: Incomplete
      neuromuscular recovery can be minimized with acceleromyographic monitoring. The
      risk of adverse respiratory events during early recovery from anesthesia can be
      reduced by intraoperative acceleromyography use.

PMID- 18719437
TI  - Transmission of pathogenic bacterial organisms in the anesthesia work area.
AB  - BACKGROUND: The current prevalence of hospital-acquired infections and evolving
      amplification of bacterial resistance are major public health concerns. A
      heightened awareness of intraoperative transmission of potentially pathogenic
      bacterial organisms may lead to implementation of effective preventative
      measures. METHODS: Sixty-one operative suites were randomly selected for
      analysis. Sterile intravenous stopcock sets and two sites on the anesthesia
      machine were decontaminated and cultured aseptically at baseline and at case
      completion. The primary outcome was the presence of a positive culture on the
      previously sterile patient stopcock set. Secondary outcomes were the number of
      colonies per surface area sampled on the anesthesia machine, species
      identification, and antibiotic susceptibility of isolated organisms. RESULTS:
      Bacterial contamination of the anesthesia work area increased significantly at
      the case conclusion, with a mean difference of 115 colonies per surface area
      sampled (95% confidence interval [CI], 62-169; P < 0.001). Transmission of
      bacterial organisms, including vancomycin-resistant enterococcus, to intravenous
      stopcock sets occurred in 32% (95% CI, 20.6-44.9%) of cases. Highly contaminated
      work areas increased the odds of stopcock contamination by 4.7 (95% CI, 1.42
      15.42; P = 0.011). Contaminated intravenous tubing was associated with a trend
      toward increased nosocomial infection rates (odds ratio, 3.08; 95% CI, 0.56-17.5;
      P = 0.11) and with an increase in mortality (95% CI odds ratio, 1.11-infinity; P
      = 0.0395). CONCLUSION: Potentially pathogenic, multidrug-resistant bacterial
      organisms are transmitted during the practice of general anesthesia to both the
      anesthesia work area and intravenous stopcock sets. Implementation of infection
      control measures in this area may help to reduce both the evolving problem of
      increasing bacterial resistance and the development of life-threatening
      infectious complications.

PMID- 18719438
TI  - Observations on surgical demand time series: detection and resolution of holiday
      variance.
AB  - BACKGROUND: Surgical scheduling is complicated by both naturally occurring and
      human-induced variability in the demand for surgical services. Surgical demand
      time series are decomposed into periodic, lagged, and linear trends with frequent
      occurrences of nonconstant variations in mean and variance. The authors used time
      series methods to model surgical demand time series in order to improve the
      scheduling of scarce surgical resources. METHODS: With institutional approval,
      the authors studied 47,752 surgeries undertaken at a large academic medical
      center. They initially extracted periodic information from the time series using
      two frequency domain techniques: the harmonic F test and the multitaper test.
      They subsequently extracted lagged (correlated) behavior using a seasonal
      autoregressive integrated moving average model. Finally, they used moving
      variance filters on the residuals to identify variance in the time series that
      coincided with major US holidays. RESULTS: Linear terms such as periodic cycles,
      trends, and daily and weekly lags explained 80% of the variance in the raw time
      series. In the residuals, the authors used moving variance filters to detect
      nonlinear variance artifacts that correlated with surgical activities on specific
      US holidays. CONCLUSIONS: After extracting linear terms, the remaining variance
      was attributable to a combination of nonlinear and unexplained random events. The
      authors used the term holiday variance to describe a specific nonlinear
      disturbance in surgical demand attributable to statutory US holidays. Resolving
      these holiday variances may assist in management and scheduling of scarce
      surgical personnel and resources.

PMID- 18719439
TI  - Motor and somatosensory evoked potentials are well maintained in patients given
      dexmedetomidine during spine surgery.
AB  - BACKGROUND: Many commonly used anesthetic agents produce a dose-dependent
      amplitude reduction and latency prolongation of evoked responses, which may
      impair diagnosis of intraoperative spinal cord injury. Dexmedetomidine is
      increasingly used as an adjunct for general anesthesia. Therefore, the authors
      tested the hypothesis that dexmedetomidine does not have a clinically important
      effect on somatosensory and transcranial motor evoked responses. METHODS: Thirty
      seven patients were enrolled and underwent spinal surgery with instrumentation
      during desflurane and remifentanil anesthesia with dexmedetomidine as an
      anesthetic adjunct. Upper- and lower-extremity transcranial motor evoked
      potentials and somatosensory evoked potentials were recorded during four defined
      periods: baseline without dexmedetomidine; two periods with dexmedetomidine (0.3
      and 0.6 ng/ml), in a randomly determined order; and a final period 1 h after drug
      discontinuation. The primary outcomes were amplitude and latency of P37/N20, and
      amplitude, area under the curve, and voltage threshold for transcranial motor
      evoked potential stimulation. RESULTS: Of the total, data from 30 patients were
      evaluated. Use of dexmedetomidine, as an anesthetic adjunct, did not have an
      effect on the latency or amplitude of sensory evoked potentials greater than was
      prespecified as clinically relevant, and though the authors were unable to claim
      equivalence on the amplitude of transcranial motor evoked responses due to
      variability, recordings were made throughout the study in all patients.
      CONCLUSION: Use of dexmedetomidine as an anesthetic adjunct at target plasma
      concentrations up to 0.6 ng/ml does not change somatosensory or motor evoked
      potential responses during complex spine surgery by any clinically significant
      amount.

PMID- 18719440
TI  - Direct assessments of the antioxidant effects of propofol medium chain
      triglyceride/long chain triglyceride on the brain of stroke-prone spontaneously
      hypertensive rats using electron spin resonance spectroscopy.
AB  - BACKGROUND: Antioxidant anesthetics such as propofol (2,6-diisopropylphenol)
      directly inhibit lipid peroxidation via the generation of reactive oxygen
      species. Currently, there are no other studies regarding the direct effects of
      propofol medium chain triglyceride/long chain triglyceride (MCT/LCT) on reactive
      oxygen species generation or in experimental models of reactive oxygen species
      induced oxidative stress in the brain. METHODS: The authors investigated the
      effects of propofol MCT/LCT on reactive oxygen species (hydroxyl radical or
      superoxide) by electron spin resonance spin trapping with 5,5-dimethyl-1
      pyrroline-N-oxide. The effects of propofol MCT/LCT on oxidative stress in the
      brain of Wistar-Kyoto rats or stroke-prone spontaneously hypertensive rats were
      investigated by using an in vivo L-band electron spin resonance system to monitor
      the decay rate of 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl as a
      nitroxyl spin probe. RESULTS: These studies provided direct evidence that
      propofol MCT/LCT inhibited hydroxyl radical generation, but not superoxide
      generation. Regarding the hydroxyl radical from the Fenton system, it is likely
      to be due to the scavenging effects of vehicle. Anesthesia with propofol MCT/LCT
      reduced the degree of the high oxidative stress in the brain of stroke-prone
      spontaneously hypertensive rats. CONCLUSION: The current data show that propofol,
      mixed with clinical reagents (propofol MCT/LCT), resulted in the down-regulation
      of high oxidative stress due to scavenging hydroxyl radical, as demonstrated by
      in vitro or in vivo electron spin resonance analysis. These results led to
      reduced levels of hydroxyl radical, formed by brain injury such as stroke, and
      may therefore provide advantages for neuroprotection during anesthesia for
      craniotomy, e.g., in cases of brain disease.

PMID- 18719442
TI  - Using permutation entropy to measure the electroencephalographic effects of
      sevoflurane.
AB  - BACKGROUND: Approximate entropy (AE) has been proposed as a measure of anesthetic
      drug effect in electroencephalographic data. Recently, a new method called
      permutation entropy (PE) based on symbolic dynamics was also proposed to measure
      the complexity in an electroencephalographic series. In this study, the AE and PE
      were applied to electroencephalographic recordings for revealing the effect of
      sevoflurane on brain activity. The dose-response relation of PE during
      sevoflurane anesthesia was compared with that of AE. METHODS: Nineteen patients'
      electroencephalographic data were collected during the induction of general
      anesthesia with sevoflurane. PE and AE were applied to the
      electroencephalographic recordings, and the performance of both measures was
      assessed by pharmacokinetic-pharmacodynamic modeling and prediction probability.
      To ensure an accurate complexity measure of electroencephalographic recordings, a
      wavelet-based preprocessor was built in advance. RESULTS: Both PE and AE could
      distinguish between the awake and anesthetized states and were highly correlated
      to each other (r = 0.8, P = 0.004). The pharmacokinetic-pharmacodynamic model
      adequately described the dose-response relation between PE and AE and sevoflurane
      effect site concentration. The coefficient R between PE and effect site
      concentration was 0.89 +/- 0.07 for all patients, compared with 0.60 +/- 0.14 for
      AE. Prediction probabilities of 0.86 +/- 0.04 and 0.79 +/- 0.09 for PE and AE
      showed that PE has a stronger ability to differentiate between the awake and
      anesthetic states. CONCLUSION: The results show that PE can estimate the
      sevoflurane drug effect more effectively than AE. This method could be applied to
      design a new electroencephalographic monitoring system to estimate sevoflurane
      anesthetic drug effect.

PMID- 18719441
TI  - Physicochemical properties, pharmacokinetics, and pharmacodynamics of a
      reformulated microemulsion propofol in rats.
AB  - BACKGROUND: A newly developed microemulsion propofol consisted of 10% purified
      poloxamer 188 and 0.7% polyethylene glycol 660 hydroxystearate. The authors
      studied the physicochemical properties, aqueous free propofol concentration, and
      plasma bradykinin generation. Pharmacokinetics and pharmacodynamics were also
      evaluated in rats. METHODS: The pH, particle size, and osmolarity of
      microemulsion propofol were measured using a pH meter, particle size analyzer,
      and cryoscopic osmometer, respectively. The aqueous free propofol and plasma
      bradykinin were measured by a dialysis method and radioimmunoassay, respectively.
      Microemulsion propofol was administered by zero-order infusion of 0.5, 1.0, and
      1.5 mg . kg . min for 20 min in 30 rats. The electroencephalographic approximate
      entropy was used as a surrogate measure of propofol effect. RESULTS: The pH,
      osmolarity, and particle size of microemulsion propofol are 7.5, 280 mOsm/l, and
      67.0 +/- 28.5 nm, respectively. The aqueous free propofol concentration in
      microemulsion propofol was 63.3 +/- 1.2 mug/ml. When mixed with human blood,
      microemulsion propofol did not generate bradykinin in plasma. Although
      microemulsion propofol had nonlinear pharmacokinetics, a two-compartment model
      with linear pharmacokinetics best described the time course of the propofol
      concentration as follows: V1 = 0.143 l/kg, k10 = 0.175 min, k12 = 0.126 min, k21
      = 0.043 min. The pharmacodynamic parameters in a sigmoid Emax model were as
      follows: E0 = 1.18, Emax = 0.636, Ce50 = 1.87 mug/ml, gamma = 1.28, ke0 = 1.02
      min. CONCLUSIONS: Microemulsion propofol produced a high concentration of free
      propofol in the aqueous phase. For the applied dose range, microemulsion propofol
      showed nonlinear pharmacokinetics.

PMID- 18719443
TI  - Novel ryanodine receptor mutation that may cause malignant hyperthermia.
AB  - BACKGROUND: Malignant hyperthermia (MH) is a hypermetabolic condition caused by a
      genetic disposition leading to increased Ca release from the sarcoplasmic
      reticulum after exposure to triggering agents. In the authors' ongoing evaluation
      of patients undergoing MH testing in Austria, they detected a family with a new
      variant of the ryanodine receptor 1. Guidelines suggest that genetic tests are
      possible only for individuals from families in which the mutations are known. The
      aim of this study was to provide functional data that establish a potential link
      between this new variant and susceptibility to MH, and thus enable application in
      genetic tests. METHODS: Messenger RNA was isolated from skeletal muscle cells
      grown in culture and used for synthesis of complementary DNA, which served as a
      template for 23 polymerase chain reactions. The sequences of all reaction
      products were analyzed. Functional studies in differentiated muscle cells
      included the Ca releasing activity of caffeine and 4-chloro-m-cresol. The authors
      measured the intracellular Ca concentration and, in combined patch clamp-Ca
      detection experiments, the voltage dependence of the Ca release. RESULTS: In a
      single family, the authors found a transition from a highly conserved thymine to
      cysteine at position 11953, leading to the exchange of tryptophan to arginine at
      position 3985. This variant was absent in 100 MH-nonsusceptible individuals.
      Functionally, cells carrying this variant were more sensitive to caffeine and 4
      chloro-m-cresol than wild-type cells and showed a shift in the voltage-dependent
      Ca release to more negative potentials. CONCLUSION: These data document a role of
      the new W3985R variant in MH susceptibility.

PMID- 18719444
TI  - Low-tidal-volume mechanical ventilation induces a toll-like receptor 4-dependent
      inflammatory response in healthy mice.
AB  - BACKGROUND: Mechanical ventilation (MV) can induce ventilator-induced lung
      injury. A role for proinflammatory pathways has been proposed. The current
      studies analyzed the roles of Toll-like receptor (TLR) 4 and TLR2 involvement in
      the inflammatory response after MV in the healthy lung. METHODS: Wild-type (WT)
      C57BL6, TLR4 knockout (KO), and TLR2 KO mice were mechanically ventilated for 4
      h. Bronchoalveolar lavage fluid was analyzed for presence of endogenous ligands.
      Lung homogenates were used to investigate changes in TLR4 and TLR2 expression.
      Cytokines were measured in lung homogenate and plasma, and leukocytes were
      counted in lung tissue. RESULTS: MV significantly increased endogenous ligands
      for TLR4 in bronchoalveolar lavage fluid and relative messenger RNA expression of
      TLR4 and TLR2 in lung tissue. In lung homogenates, MV in WT mice increased levels
      of keratinocyte-derived chemokine, interleukin (IL)-1alpha, and IL-1beta. In TLR4
      KO mice, MV increased IL-1alpha but not IL-1beta, and the increase in
      keratinocyte-derived chemokine was less pronounced. In plasma, MV in WT mice
      increased levels of IL-6, keratinocyte-derived chemokine, and tumor necrosis
      factor alpha. In TLR4 KO mice, MV did not increase levels of IL-6 or tumor
      necrosis factor alpha, and the response of keratinocyte-derived chemokine was
      less pronounced. MV in TLR2 KO mice did not result in different cytokine levels
      compared with WT mice. In WT and TLR2 KO mice, but not in TLR4 KO mice, MV
      increased the number of pulmonary leukocytes. CONCLUSIONS: The current study
      supports a role for TLR4 in the inflammatory reaction after short-term MV in
      healthy lungs. Increasing the understanding of the innate immune response to MV
      may lead to future treatment advances in ventilator-induced lung injury, in which
      TLR4 may serve as a therapeutic target.

PMID- 18719445
TI  - Guidance of block needle insertion by electrical nerve stimulation: a pilot study
      of the resulting distribution of injected solution in dogs.
AB  - BACKGROUND: Little is known regarding the final needle tip location when various
      intensities of nerve stimulation are used to guide block needle insertion.
      Therefore, in control and hyperglycemic dogs, the authors examined whether lower
      intensity stimulation results in injection closer to the sciatic nerve than
      higher-threshold stimulation. METHODS: During anesthesia, the sciatic nerve was
      approached with an insulated nerve block needle emitting either 1 mA (high
      current group, n = 9) or 0.5 mA (low-current group, n = 9 in control dogs and n =
      6 in hyperglycemic dogs). After positioning to obtain a distal motor response,
      the lowest current producing a response was identified, and ink (0.5 ml) was
      injected. Frozen sections of the tissue revealed whether the ink was in contact
      with the epineurium of the nerve, distant to it, or within it. RESULTS: In
      control dogs, the patterns of distribution using high-threshold (final current
      0.99 +/- 0.03 mA, mean +/- SD) and low-threshold (final current 0.33 +/- 0.08 mA)
      stimulation equally showed ink that was in contact with the epineurium or distant
      to it. One needle placement in the high-threshold group resulted in intraneural
      injection. In hyperglycemic dogs, all needle insertions used a low-threshold
      technique (n = 6, final threshold 0.35 +/- 0.08 mA), and all resulted in
      intraneural injections. CONCLUSIONS: In normal dogs, current stimulation levels
      in the range of 0.33-1.0 mA result in needle placement comparably close to the
      sciatic nerve but do not correlate with distance from the target nerve. In this
      experimental design, low-threshold electrical stimulation does not offer
      satisfactory protection against intraneural injection in the presence of
      hyperglycemia.

PMID- 18719446
TI  - Electrical impedance to distinguish intraneural from extraneural needle placement
      in porcine nerves during direct exposure and ultrasound guidance.
AB  - BACKGROUND: Intraneural injection during peripheral nerve blockade can cause
      neurologic injury. Current approaches to prevent or detect intraneural injection
      lack reliability and consistency, or only signal intraneural injection upon the
      event. A change in electrical impedance (EI) could be indicative of intraneural
      needle placement before injection. METHODS: After animal care committee approval,
      eight pigs were anesthetized and kept spontaneously breathing. In four pigs (part
      1), the sciatic nerves were exposed bilaterally for direct needle placement; in a
      further four pigs (part 2), the tissue was kept intact for ultrasound-guided
      needle placement. An insulated needle (Sprotte 24 gauge; Pajunk GmbH
      Medizintechnologie, Geisingen, Germany), attached to a nerve stimulator
      displaying EI (Braun Stimuplex HNS 12; B. Braun Medical, Bethlehem, PA), was
      placed extraneurally and then advanced to puncture the nerve sheath. Five
      punctures within approximately a 1-cm length of each nerve were performed. For
      each Part, overall EI at each compartment and EI after individual punctures were
      compared using a general linear model, with post hoc analysis using the Duncan
      multiple range test. RESULTS: The EI was lower extraneurally compared with
      intraneurally during open dissection (12.1 +/- 1.8 vs. 23.2 +/- 4.4 kOmega; P <
      0.0001; n = 8) and when using ultrasound guidance (10.8 +/- 2.9 vs. 18.2 +/- 6.1
      kOmega; P < 0.0001; n = 7 nerves were visualized adequately). The EI difference
      was maintained despite performing five sequential punctures. CONCLUSIONS: With
      further study, EI could prove to be a quantifiable warning signal to alert
      clinicians to intraneural needle placement, preventing local anesthetic injection
      and subsequent nerve injury.

PMID- 18719447
TI  - Antiinflammatory effect of peripheral nerve blocks after knee surgery: clinical
      and biologic evaluation.
AB  - BACKGROUND: Nerve blocks provide analgesia after surgery. The authors tested
      whether nerve blocks have antiinflammatory effects. METHODS: Patients had
      combined sciatic (single-shot) and continuous femoral block (48 h) (block group)
      or morphine patient-controlled analgesia after total knee arthroplasty. Pain at
      rest and upon movement was monitored at 1 (D1), 4 (D4), and 7 days (D7) and 1
      (M1) and 3 months (M3) after surgery. Knee inflammation was evaluated (skin
      temperature, knee circumference) before surgery and at D1, D4, D7, M1, and M3.
      Plasma cytokine concentrations (interleukin [IL]-6, IL-1beta, tumor necrosis
      factor [TNF], IL-10, soluble receptor 1 of TNF [sTNF-R1]) were measured before
      surgery and at 4 h, D1, D4, and D7 after surgery. Capsule and synovial membrane
      cytokines were measured (IL-6, TNF, IL-1, IL-10). Knee flexion was evaluated
      before surgery and at D1, D4, D7, M1, and M3. Morphine use and recovery time to
      autonomy were monitored. RESULTS: Pain at rest and upon movement was lower in the
      block group than in patient-controlled analgesia patients between D1 and D7
      (analysis of variance, P < 0.005). Knee flexion was improved in the block group
      for D1 to M1 (analysis of variance, P < 0.0001). Block group patients recovered
      nonassisted mobilization (t test, P = 0.04) and toilet use (t test, P = 0.03)
      more rapidly. Knee circumference and skin temperature were lower in the block
      group between D1 and D7 (analysis of variance, P < 0.05). Synovial membrane IL-1
      (P < 0.05) and IL-10 (P < 0.01) increased, and plasma IL-6 and sTNF-R1 peaked at
      24 h, with no difference between groups. CONCLUSION: Nerve blocks inhibited
      clinical inflammation after total knee arthroplasty, with no change in tissue and
      plasma cytokine concentrations.

PMID- 18719448
TI  - Ambulatory continuous posterior lumbar plexus nerve blocks after hip
      arthroplasty: a dual-center, randomized, triple-masked, placebo-controlled trial.
AB  - BACKGROUND: The authors tested the hypotheses that after hip arthroplasty,
      ambulation distance is increased and the time required to reach three specific
      readiness-for-discharge criteria is shorter with a 4-day ambulatory continuous
      lumbar plexus block (cLPB) than with an overnight cLPB. METHODS: A cLPB
      consisting of 0.2% ropivacaine was provided from surgery until the following
      morning. Patients were then randomly assigned either to continue ropivacaine or
      to be switched to normal saline. Primary endpoints included (1) time to attain
      three discharge criteria (adequate analgesia, independence from intravenous
      analgesics, and ambulation > or = 30 m) and (2) ambulatory distance in 6 min the
      afternoon after surgery. Patients were discharged with their cLPB and a portable
      infusion pump, and catheters were removed on the fourth postoperative day.
      RESULTS: Patients given 4 days of perineural ropivacaine (n = 24) attained all
      three discharge criteria in a median (25th-75th percentiles) of 29 (24-45) h,
      compared with 51 (42-73) h for those of the control group (n = 23; estimated
      ratio = 0.62; 95% confidence interval, 0.45-0.92; P = 0.011). Patients assigned
      to receive ropivacaine ambulated a median of 34 (9-55) m the afternoon after
      surgery, compared with 20 (6-46) m for those receiving normal saline (estimated
      ratio = 1.3; 95% confidence interval, 0.6-3.0; P = 0.42). Three falls occurred in
      subjects receiving ropivacaine (13%), versus none in subjects receiving normal
      saline. CONCLUSIONS: Compared with an overnight cLPB, a 4-day ambulatory cLPB
      decreases the time to reach three predefined discharge criteria by an estimated
      38% after hip arthroplasty. However, the extended infusion did not increase
      ambulation distance to a statistically significant degree.

PMID- 18719449
TI  - Perineural administration of dexmedetomidine in combination with bupivacaine
      enhances sensory and motor blockade in sciatic nerve block without inducing
      neurotoxicity in rat.
AB  - BACKGROUND: The current study was designed to test the hypothesis that high-dose
      dexmedetomidine added to local anesthetic would increase the duration of sensory
      and motor blockade in a rat model of sciatic nerve blockade without causing nerve
      damage. METHODS: Thirty-one adult Sprague-Dawley rats received bilateral sciatic
      nerve blocks with either 0.2 ml bupivacaine, 0.5%, and 0.5% bupivacaine plus
      0.005% dexmedetomidine in the contralateral extremity, or 0.2 ml dexmedetomidine,
      0.005%, and normal saline in the contralateral extremity. Sensory and motor
      function were assessed by a blinded investigator every 30 min until the return of
      normal sensory and motor function. Sciatic nerves were harvested at either 24 h
      or 14 days after injection and analyzed for perineural inflammation and nerve
      damage. RESULTS: High-dose dexmedetomidine added to bupivacaine significantly
      enhanced the duration of sensory and motor blockade. Dexmedetomidine alone did
      not cause significant motor or sensory block. All of the nerves analyzed had
      normal axons and myelin at 24 h and 14 days. Bupivacaine plus dexmedetomidine
      showed less perineural inflammation at 24 h than the bupivacaine group when
      compared with the saline control. CONCLUSION: The finding that high-dose
      dexmedetomidine can safely improve the duration of bupivacaine-induced
      antinociception after sciatic nerve blockade in rats is an essential first step
      encouraging future studies in humans. The dose of dexmedetomidine used in this
      study may exceed the sedative safety threshold in humans and could cause
      prolonged motor blockade; therefore, future work with clinically relevant doses
      is necessary.

PMID- 18719450
TI  - Analgesic effects of Sazetidine-A, a new nicotinic cholinergic drug.
AB  - BACKGROUND: The use of nicotinic agonists for analgesia is limited by their
      unacceptable side effects. Sazetidine-A is a new partial agonist nicotinic ligand
      that has very high selectivity for beta2-containing nicotinic acetylcholine
      receptors. It potently and selectively desensitizes alpha4beta2 nicotinic
      acetylcholine receptors without measurable effects on alpha3beta4 receptors. The
      authors investigated the analgesic effects of Sazetidine-A using the formalin
      model of chronic inflammatory pain. METHODS: The formalin test was conducted
      after rats received intraperitoneal saline, Sazetidine-A (0.125, 0.25, 0.5, 1, 2
      mg/kg), or subcutaneous epibatidine (2.5-5-10 mug/kg). In other experiments,
      Sazetidine-A was preceded by naloxone (0.5 mg/kg) or mecamylamine (10 mg).
      Effects of Sazetidine-A and epibatidine on locomotor were tested in an open
      field, and seizure activity was measured using the Racine scale. Locus coeruleus
      neuron extracellular single-unit spontaneous discharge was recorded in
      anesthetized animals after Sazetidine-A and epibatidine. RESULTS: Higher doses of
      Sazetidine-A (0.5, 1, or 2 mg/kg) induced analgesia, with pain scores
      significantly lower than those seen after saline, lower doses of Sazetidine-A,
      and epibatidine (P < 0.001). Naloxone did not antagonize the effects of
      Sazetidine-A, and mecamylamine had partial, dose-dependent antagonistic effects.
      Epibatidine excited locus coeruleus neurons, whereas Sazetidine-A had no effect
      on these neurons. Epibatidine and Sazetidine-A affected animals' locomotor
      activity for the initial 20 min. While analgesic doses of epibatidine caused
      seizures, no seizure activity or other neurologic complications were seen in
      animals that received as much as four times the minimum analgesic dose of
      Sazetidine-A. CONCLUSIONS: Sazetidine-A seems to be a potent analgesic without
      causing neurologic side effects.

PMID- 18719451
TI  - A118G single nucleotide polymorphism of human mu-opioid receptor gene influences
      pain perception and patient-controlled intravenous morphine consumption after
      intrathecal morphine for postcesarean analgesia.
AB  - BACKGROUND: Previous studies have shown that genetic variability at position 118
      of the human mu-opioid receptor gene altered patients' response to intravenous
      morphine. The purpose of this study was to investigate whether this polymorphism
      contributes to the variability in response to morphine for postcesarean
      analgesia. METHODS: After investigators obtained informed consent, 588 healthy
      women received 0.1 mg intrathecal morphine for postcesarean analgesia. Their
      blood samples were genotyped for the A118G polymorphism-A118 homozygous (AA),
      heterozygous (AG), or homozygous for the G allele (GG). Pain scores, the severity
      of nausea and vomiting, the incidence of pruritus, and the total self
      administered intravenous morphine were recorded for the first 24 postoperative
      hours. RESULTS: Two hundred seventy women (46%) were AA, 234 (40%) were AG, and
      82 (14%) were GG. The 24-h self-administered intravenous morphine consumption was
      lowest in the AA group (P = 0.001; mean, 5.9; 95% confidence interval, 5.1-6.8)
      versus the AG (8.0; 6.9-9.1) and GG groups (9.4; 7.3-11.5). Pain scores were
      lowest in the AA group and highest in the GG group, with a statistically
      significant difference detected between AA, AG, and GG (P = 0.049). Total
      morphine consumption was also influenced by patients' age and paying status. AA
      group was associated with the highest incidence of nausea (26 of 272 [9.6%]; P =
      0.02) versus the other two groups (13 of 234 [5.6%] and 1 of 82 [1.2%] for AG and
      GG, respectively). CONCLUSION: Genetic variation at position 118 of the mu-opioid
      receptor is associated with interindividual differences in pain scores, self
      administered intravenous morphine, and the incidence of nausea postoperatively.

PMID- 18719452
TI  - Radiofrequency applications to dorsal root ganglia: a literature review.
AB  - Application of radiofrequency currents to the dorsal root ganglia, in the
      treatment of various pain syndromes, has been clinically practiced for more than
      30 yr. The clinical efficacy and the safety of this technique, however, remain
      poorly understood. The authors reviewed the literature on this modality of pain
      relief to determine its clinical efficacy, safety, and mechanisms of action. The
      two modalities in common clinical use were pulsed and continuous mode
      radiofrequency. These techniques were generally found to be safe, and the
      majority of the observational studies reported their clinical efficacy. Five
      randomized controlled trials evaluated their clinical use; these trials were
      relatively short-termed and small in size, and their results were variable. The
      mechanism of action of these techniques was unclear. Larger controlled clinical
      trials evaluating the long-term effects of these techniques and basic science
      research to determine their precise mode of action are needed.

PMID- 18719454
TI  - Application of a newly designed right-sided, double-lumen endobronchial tube in
      patients with a very short right mainstem bronchus.

PMID- 18719455
TI  - Abnormal bleeding after an oral surgical procedure leading to airway compromise
      in a patient taking a selective serotonin reuptake inhibitor and a nonsteroidal
      antiinflammatory drug.

PMID- 18719456
TI  - Acetaminophen-induced, not desflurane-induced, hepatotoxicity.

PMID- 18719457
TI  - Two cases with past and family history of febrile convulsion developed seizure
      like movements during sevoflurane anesthesia.

PMID- 18719460
TI  - Hyperthermia warning.

PMID- 18719453
TI  - Intracarotid delivery of drugs: the potential and the pitfalls.
AB  - The major efforts to selectively deliver drugs to the brain in the past decade
      have relied on smart molecular techniques to penetrate the blood-brain barrier,
      whereas intraarterial drug delivery has drawn relatively little attention.
      Meanwhile, rapid progress has been made in the field of endovascular surgery.
      Modern endovascular procedures can permit highly targeted drug delivery by the
      intracarotid route. Intracarotid drug delivery can be the primary route of drug
      delivery or it could be used to facilitate the delivery of smart
      neuropharmaceuticals. There have been few attempts to systematically understand
      the kinetics of intracarotid drugs. Anecdotal data suggest that intracarotid drug
      delivery is effective in the treatment of cerebral vasospasm, thromboembolic
      strokes, and neoplasms. Neuroanesthesiologists are frequently involved in the
      care of such high-risk patients. Therefore, it is necessary to understand the
      applications of intracarotid drug delivery and the unusual kinetics of
      intracarotid drugs.

PMID- 18719476
TI  - Take baby steps to reach breastfeeding goals.

PMID- 18719488
TI  - Acute abdomen: what a pain!
AB  - So many things-some life-threatening-can cause abdominal pain. Here's how to
      capture the clues quickly and accurately.

PMID- 18719487
TI  - Targeted cancer. These "smart weapons" hit cancer in novel ways.
AB  - Be prepared to recognize and manage a new collection of adverse reactions that
      may arise from these innovative approaches to cancer therapy.

PMID- 18719490
TI  - Monitoring your adult patient with bedside pulse oximetry.

PMID- 18719491
TI  - Patient education series. Kidney dialysis.

PMID- 18719492
TI  - Drawing support from a writing group.
AB  - Make sure you're all on the same page by following these guidelines.

PMID- 18719493
TI  - Double trouble: when delirium complicates dementia.
AB  - Learn to protect a patient with dementia from the disabling effects of delirium.

PMID- 18719498
TI  - Managing cellulitis and impetigo.

PMID- 18719499
TI  - Pediatric nurse fliers to the rescue.

PMID- 18719500
TI  - Closing in on Chlamydia.

PMID- 18719501
TI  - Fish story.
AB  - We've all heard the expression "laughter is the best medicine." Over the years,
      scientific evidence has corroborated the therapeutic value of laughter, which has
      been shown to lower BP and heart rate, improve lung capacity, improve memory and
      alertness, reduce pain, aid digestion, and lower levels of stress hormones.But
      during a hectic workday, as we witness the worries and sufferings of others, we
      often forget to laugh. Indeed, we wonder if it's even appropriate. How could we
      laugh in such troubled times? This true story from Chicken Soup for the Nurse's
      Soul, Second Dose, reminds us that laughter is good for the patient's soul too.

PMID- 18719502
TI  - Creating a professional portfolio.

PMID- 18719504
TI  - Bee sting reaction.

PMID- 18719505
TI  - Determinants of quality of life in irritable bowel syndrome.
AB  - OBJECTIVES: Health-related quality of life (HRQOL) is a main outcome in irritable
      bowel syndrome (IBS), but most studies have been conducted on moderate-severe
      patients. We sought to ascertain the relative contribution of severity, anxiety,
      and personality to impairment of HRQOL in a sample representative of the entire
      IBS spectrum. MATERIALS AND METHODS: IBS consulters, IBS nonconsulters, and
      controls were invited to complete questionnaires designed to measure severity of
      IBS (Functional Bowel Disease Severity Index), anxiety (State-trait Anxiety
      Inventory), personality (Minnesota Multiphasic Personality Inventory-2), and
      HRQOL [Short Form 36 (SF-36)]. The SF-36 scores of the study groups were
      compared, and a multiple regression model was constructed. RESULTS: Sixty-six IBS
      consulters, 70 nonconsulters, and 117 controls were studied. All 3 groups
      differed in terms of SF-36 physical (46.5+/-9.4 vs. 50.5+/-8.0 vs. 54.5+/-6.0)
      and mental composite scores (38.2+/-12.5 vs. 43.2+/-12.0 vs. 46.7+/-10.6).
      Although physical scores were linked to hypochondriasis (beta=-0.39; P<0.001),
      severity of pain (beta=-0.28; P<0.001), and age, mental scores were associated
      with state anxiety (beta=-0.36; P<0.001) and trait anxiety (beta=-0.40; P<0.001).
      CONCLUSIONS: HRQOL is impaired in all subgroups of IBS sufferers, with the degree
      of impairment depending mostly on symptom severity and psychologic factors
      (hypochondriasis and anxiety).

PMID- 18719506
TI  - Frequency, behavior, and prognostic implications of antimitochondrial antibodies
      in type 1 autoimmune hepatitis.
AB  - BACKGROUND: Antimitochondrial antibodies (AMA) can occur in autoimmune hepatitis,
      but their durability and prognostic significance are uncertain. OBJECTIVES:
      Determine the frequency, behavior, and prognostic implications of AMA in type 1
      autoimmune hepatitis. METHODS: One hundred thirty patients were tested for AMA by
      the same enzyme-linked immunosorbent assay at accession and during 123+/-9 months
      of observation (mean, 6+/-0.2 determinations/patient). Findings were correlated
      with clinical and histologic features and treatment outcomes. RESULTS: Twenty
      four patients (18%) had AMA, including 17 who had the antibodies at accession
      (71%) and 7 who developed them during follow-up (29%). AMA persisted in 13
      patients (54%) who were tested on 5+/-1 occasions during 141+/-33 months.
      Cholestatic histologic features occurred as commonly in patients with and without
      AMA at presentation (18% vs. 10%, P=0.4). AMA disappeared in 4 patients, and they
      developed in 7 patients after 34+/-7 months. Late expression of antibodies was
      not associated with a higher frequency of cholestatic histologic changes than
      continued seronegativity (14% vs. 9%, P=0.5). Remission (83% vs. 76%, P=0.4) and
      treatment failure (8% vs. 11%, P>0.9) occurred as commonly in both groups.
      CONCLUSIONS: AMA can appear and disappear. They do not identify a subgroup that
      requires different treatment or that evolves quickly into a cholestatic syndrome.

PMID- 18719507
TI  - Plastic versus self-expanding metallic stents for malignant hilar biliary
      obstruction: a prospective multicenter observational cohort study.
AB  - BACKGROUND: There are few comparative data as to whether plastic or self
      expanding metallic stents are preferable for palliating malignant hilar biliary
      obstruction. METHODS: Thirty-day outcomes of consecutive endoscopic retrograde
      cholangiopancreatographies performed for malignant hilar obstruction at 6 private
      and 5 university centers were assessed prospectively. RESULTS: Patients receiving
      plastic (N=28) and metallic stents (N=34) were similar except that metallic stent
      recipients more often had: Bismuth III or IV tumors (16/34 vs. 5/28 P=0.043),
      higher Charlson comorbidity scores (P=0.003), metastatic disease (P=0.006), and
      management at academic centers (P=0.018). The groups had similar rates of
      bilateral stent placement (4/28 vs. 5/34), and similar frequency of opacified but
      undrained segmental ducts (7/28 vs. 5/34). Adverse outcomes including
      cholangitis, stent occlusion, migration, perforation, and/or the need for
      unplanned endoscopic retrograde cholangiopancreatography or percutaneous
      transhepatic cholangiography occurred in 11/28 (39.3%) patients with plastic
      versus 4/34 (11.8%) with metal stents (P=0.017). By logistic regression, factors
      associated with adverse outcomes included plastic stent placement (odds ratio
      6.32; 95% confidence interval 1.23, 32.56) and serum bilirubin (1.11/mg/dL above
      normal: 1.01, 1.22) but not center type or Bismuth class. CONCLUSIONS: Metallic
      stent performance was superior to plastic for hilar tumor palliation with respect
      to short-term outcomes, independent of disease severity, Bismuth class, or
      drainage quality.

PMID- 18719508
TI  - Esophageal acid exposure on proton pump inhibitors in unselected asymptomatic
      gastroesophageal reflux disease patients.
AB  - BACKGROUND AND AIM: Efficacy of proton pump inhibitors (PPIs) on symptoms of
      gastroesophageal reflux (GER) is supposed to result from normalization of
      esophageal acid exposure; however, recent data in selected severe patients have
      challenged this concept. The aim of the study was to investigate 24-hour
      esophagogastric pH in unselected patients with GER disease in symptomatic
      remission during PPIs. METHODS: Thirty of the 31 consecutive patients with
      heartburn enrolled achieved adequate symptom control (<or=1 heartburn episode/wk)
      on PPIs o.d. (n=22) or b.d. (n=8); 3 refused pH monitoring, thus 27 tracings were
      analyzed. RESULTS: Medians (Interquartile Range); Intragastric tracings showed a
      wide range of inhibition of acid secretion, 61.2% (49.7% to 80.2%) time at pH>4,
      nocturnal acid breakthrough being shorter (P=0.03) on PPIs b.d. compared with
      PPIs o.d., 125 minutes (90 to 247) versus 253 minutes (210 to 340). Esophageal
      acid exposure was 3.3% (1.4% to 7.9%) time at pH<4, 9 patients having increased
      exposure (ie, >5.5%), 7 of whom on PPIs o.d. Patients with increased acid GER on
      PPIs had a higher prevalence of esophagitis (67% vs. 22%, P<0.05) and hiatus
      hernia (78% vs. 39%, P<0.1) at endoscopy off PPIs. CONCLUSIONS: One third of
      unselected patients with GER disease asymptomatic on PPIs have an increased
      esophageal acid exposure, especially if their PPI is administered o.d.

PMID- 18719509
TI  - Identification of patients at increased risk for colorectal cancer in an open
      access endoscopy center.
AB  - GOALS: To determine whether patients referred for open access endoscopy (OAE) are
      being appropriately identified as "increased risk" or "average risk" for
      colorectal cancer (CRC) by referring physicians. BACKGROUND: OAE allows
      nongastroenterologists to schedule elective endoscopies without prior
      consultation with a gastroenterologist. It is unknown how accurately referring
      physicians identify CRC risk of such patients. METHODS: We retrospectively
      reviewed the records of outpatients referred to a single OAE center for screening
      or surveillance colonoscopy from July 1, 2001 to November 8, 2002. Before
      colonoscopy, a 3-question tool was used to stratify each patient as average risk
      or increased risk for CRC. CRC risk assessment was compared with the referring
      physician's indication for colonoscopy. Chi-square testing was used to compare
      the incidence of neoplastic polyps between average risk and increased risk
      patients. RESULTS: Two hundred eighty-eight patients met inclusion criteria.
      Referring physicians accurately identified 61% of 126 increased risk patients,
      including 13 of 19 patients (68%) with a personal history of CRC, 29 of 61
      patients (48%) with a family history of CRC, 47 of 61 patients (77%) with a
      personal history of colonic polyps, and 0 of 8 patients (0%) who met clinical
      criteria for hereditary nonpolyposis colorectal cancer. Adenomatous polyps were
      found in 24% of average risk patients compared with 41% of increased risk
      patients (P<0.01). CONCLUSIONS: In an OAE system, referring physicians often fail
      to correctly identify patients at increased risk for CRC. Our 3-question tool for
      risk assessment helps to better identify patients at increased risk of CRC and
      can be used by gastroenterologists to stratify patients referred for OAE.

PMID- 18719510
TI  - Primary gastrointestinal follicular lymphoma: a clinicopathologic study of 13
      cases from Taiwan.
AB  - GOALS: Follicular lymphoma (FL) is a common nodal lymphoma. Primary
      gastrointestinal follicular lymphoma (GIFL) is rare and most commonly occurs in
      the elder women with indolent clinical course, mainly in the duodenum and
      terminal ileum. We conducted this study to characterize GIFL in Taiwan. STUDY: A
      total of 13 cases were retrospectively collected in 4 hospitals in southern and
      eastern Taiwan up to 2006. Pathology review and immunohistochemistry were
      performed and the clinical data were obtained from chart review. RESULTS: There
      were 5 men and 8 women with a median age of 58 years (range, 31 to 74; mean, 55).
      The most frequent site was ileum (7/13, 54%) with 4 tumors in the terminal ileum
      and the most common symptom was abdominal pain (8/13, 62%). Multiple lymphomatous
      polyposis was present in 6 patients (46%). Five (45%) of 11 tumors with surgical
      resection showed transmural involvement. Most of the cases revealed a
      predominantly follicular pattern (7/13, 54%) and low-grade disease (grades 1 and
      2; 10/13, 77%). The tumors expressed CD10 (62%), Bcl-2 (77%), Bcl-6 (77%), and
      MUM1 (38%). Five patients (38%) were at stage IE and 8 (62%) at stage IIE.
      Treatment included surgery with or without chemotherapy. All patients achieved
      complete remission and relapse occurred in 3 patients. At a median follow-up time
      of 51 months (range, 3 to 180; mean, 63), 11 patients (85%) were disease free and
      no patient died of lymphoma. CONCLUSIONS: We characterized the clinicopathologic
      features of the first series of GIFL in Taiwan. These tumors frequently involved
      ileum with a favorable prognosis.

PMID- 18719511
TI  - Self-expandable metallic stents for palliative treatment of digestive cancer.
AB  - BACKGROUND/GOAL: Self-expandable metallic stents can be used to reestablish
      luminal continuity in patients with malignancy of the esophagus, gastric outlet,
      or colon who are at high risk for surgical intervention. Data regarding their
      complication profiles remain incomplete. Our aim was to evaluate the feasibility
      and complications of endoscopic stenting in esophageal, gastroduodenal, and
      colonic malignancies. STUDY: Between January 2003 and December 2005, 153 patients
      underwent 182 endoscopic procedures for insertion of 199 metallic stents in a
      single referral center. Complications were assessed retrospectively. RESULTS: The
      mean follow-up was 170 days. The mortality was 73.9% (113 patients), 105 cases
      between 1 and 60 weeks after the procedure (median survival, 17 wk), but none
      directly related to the stent placement. One single stent was required in 115
      (75%) patients, and 37 (24.2%) cases required an overlapping stent. The procedure
      was unsuccessful in only 1 case of colonic obstruction. Thirty-eight (26.6%)
      patients developed 52 complications, of which 16 (9.4%) procedure-related
      complications (perforation, 5; migration, 5; obstruction, 3; misplacement, 2; and
      hemorrhage, 1) and 36 (21.3%) late complications (obstruction, 20; migration, 9;
      fistula, 6; and perforation, 1). Eight (5.6%) patients experienced more than 1
      complication. Five (3.5%) cases required surgery (colon: 2 perforations, 1
      fistula, and 1 obstruction; esophagus: 1 perforation). No significant difference
      on the complication rates was found for any site in which a metallic stent was
      inserted. CONCLUSIONS: Endoscopic stenting for palliation of digestive cancer,
      despite a reasonable complication rate, is feasible in most patients. Most
      dysfunctions are not life-threatening and can be managed endoscopically.

PMID- 18719512
TI  - Rhythmic and spatial abnormalities of gastric slow waves in patients with
      functional dyspepsia.
AB  - OBJECTIVE: The objectives of this study were to assess differences in gastric
      slow waves measured by a newly approved multichannel electrogastrogram (EGG)
      device between patients with functional dyspepsia (FD) and healthy controls.
      MATERIALS AND METHODS: Gastric myoelectrical activity was measured by
      multichannel EGG for 1 hour preprandially and for 2 hours postprandially in 72 FD
      patients and 16 healthy volunteers. Computerized spectral analysis methods were
      used to compute various EGG parameters. RESULTS: (1) Multichannel EGG was
      abnormal in 83.3% of patients. (2) The regularity of the gastric slow wave was
      significantly lower in the FD patients in both fasting and fed states; the lowest
      regularity was seen in channel 3. (3) There was a significantly higher incidence
      of arrhythmia and tachygastria in FD patients. The highest percentage of
      arrhythmia and tachygastria were both seen in channel 3. (4) The FD patients
      showed a significantly lower percentage of slow wave coupling among the 4-channel
      EGGs in the fed state. (5) The postprandial-preprandial power ratio was
      significantly less in FD patients. (6) These patients had high symptom scores
      particularly to nausea, upper abdominal pain, and bloating. However, no
      significant correlation was noted between the EGG parameters and the symptoms.
      CONCLUSIONS: Gastric myoelectrical activity is impaired in most patients with FD.
      The impairment is reflected as a decreased percentage of normal slow waves and an
      excessive amount of arrhythmia as well as an abnormal spatial distribution of EGG
      parameters among the 4 channels, suggesting an impaired coordination of gastric
      slow waves.

PMID- 18719513
TI  - Functional dyspepsia: not all roads seem to lead to rome.
AB  - BACKGROUND: The Rome criteria have been introduced to create order in the
      heterogeneity of functional dyspepsia. The applicability of these symptom-based
      classification systems remains controversial. GOAL: To evaluate the successive
      Rome criteria for functional dyspepsia in a large pool of patients with
      endoscopically verified functional dyspepsia. STUDY: Patients referred to a
      secondary care district hospital were asked to fill out a questionnaire on
      gastrointestinal symptoms 2 weeks before upper gastrointestinal endoscopy.
      Patients were classified according to the Rome I, II, and III criteria for
      functional dyspepsia. RESULTS: Nine hundred and twelve (70%) patients had no
      organic disorder explaining their symptoms. According to the Rome I, II, and III
      criteria, 371 (41%), 735 (81%), and 551 (60%) of these patients had functional
      dyspepsia, respectively. Twenty-five percent of patients had functional dyspepsia
      according to all 3 Rome criteria, whereas 15% was not classifiable at all. Forty
      four percent and 42% of the patients, respectively, had epigastric pain syndrome
      and postprandial distress syndrome according to the Rome III criteria; however,
      26% of all patients met both criteria and 40% was not classified at all.
      CONCLUSIONS: The symptom-based Rome classification of functional dyspepsia does
      not lead to an easily applicable and consistent system that is useful in clinical
      practice or scientific research.

PMID- 18719514
TI  - Prevalence of small intestine bacterial overgrowth diagnosed by quantitative
      culture of intestinal aspirate in celiac disease.
AB  - BACKGROUND AND AIM: A recent study using lactulose hydrogen-breath testing
      suggests that small intestine bacterial overgrowth (SIBO) is a common cause of
      nonresponsive celiac disease (CD). The prevalence of SIBO in CD diagnosed by
      quantitative culture of intestinal aspirate is unknown. The aim of this study is
      to evaluate the prevalence and significance of SIBO in CD based on the results of
      quantitative culture of intestinal aspirate. METHODS: We studied patients with CD
      in whom culture of intestinal aspirate was evaluated for the presence of
      anaerobes and aerobes. Bacterial overgrowth was diagnosed if culture demonstrated
      >10 colony forming units/mL. The causes of nonresponsive CD were investigated.
      RESULTS: We included 149 biopsy-confirmed CD patients. The intestinal aspirate
      was collected in 79 (53%) patients with nonresponsive CD, 47 (32%) as initial
      work-up for malabsorption, and in 23 (15%) asymptomatic treated CD. SIBO was
      diagnosed in 14 (9.3%). Nine (11%) with nonresponsive CD, 5 (11%) at initial work
      up for malabsorption, and 0 in asymptomatic treated CD. Patients with a positive
      culture had evidence of worse malabsorption. A coexistent disorder was found in
      67% of patients with both nonresponsive CD and bacterial overgrowth. CONCLUSIONS:
      The prevalence of SIBO diagnosed by quantitative culture of intestinal aspirate
      was 9.3% in patients with CD. Patients with symptomatic treated or untreated CD
      were affected. SIBO may coexist with other disorders associated with
      nonresponsive CD.

PMID- 18719515
TI  - Mastoid and epitympanic bony obliteration in pediatric cholesteatoma.
AB  - OBJECTIVE: The primary goal of cholesteatoma surgery is complete eradication of
      the disease. To lower the recurrence rate in the pediatric population in canal
      wall up techniques and to avoid the disadvantages of canal wall down techniques,
      the bony obliteration technique with epitympanic and mastoid obliteration has
      been developed. The objective of this study was to evaluate the long-term
      surgical outcome and recurrence rate of this technique in children. STUDY DESIGN:
      Retrospective case review. SETTING: : Tertiary referral center. PATIENTS: Fifty
      two children (<16 yr) were operated on in 90.4% (n = 47) for a primary or
      recurrent cholesteatoma and in 9.6% (n = 5) for an unstable cavity. INTERVENTION:
      In all cases, we closed the tympanoattical barrier and the posterior tympanotomy
      with sculpted cortical bone and then completed obliteration of the epitympanum
      and mastoid with bone pate. A reconstruction of the middle ear was performed by
      means of an allograft tympanic membrane including the malleus handle and a
      sculpted allograft malleus or incus for columellar reconstruction. MAIN OUTCOME
      MEASURES: Recurrent rate; residual rate; functional outcome; hygienic status of
      the ear; long-term safety issues. RESULTS: The mean follow-up time was 49.5
      months (range, 12-101.3 mo). Recurrent cholesteatoma occurred in 1.9% (n = 1).
      Residual cholesteatoma was detected in 15.4% (n = 8) of the cases. Postoperative
      hearing results revealed a median gain on pure-tone averages of 14.3 dB and a
      median postoperative air-bone gap of 25.6 dB. CONCLUSION: The mastoid and
      epitympanic BOT is an effective technique to lower the recurrence rate of
      cholesteatoma in the pediatric population. Follow-up by magnetic resonance
      imaging provides a safe, noninvasive method for postoperative detection of
      residual cholesteatoma.

PMID- 18719516
TI  - Enhanced absorption and growth inhibition with amino acid monoester prodrugs of
      floxuridine by targeting hPEPT1 transporters.
AB  - A series of amino acid monoester prodrugs of floxuridine was synthesized and
      evaluated for the improvement of oral bioavailability and the feasibility of
      target drug delivery via oligopeptide transporters. All floxuridine 5'-amino acid
      monoester prodrugs exhibited PEPT1 affinity, with inhibition coefficients of Gly
      Sar uptake (IC50) ranging from 0.7 - 2.3 mM in Caco-2 and 2.0 - 4.8 mM in AsPC-1
      cells, while that of floxuridine was 7.3 mM and 6.3 mM, respectively. Caco-2
      membrane permeabilities of floxuridine prodrugs (1.01 - 5.31 x 10(-6 )cm/sec) and
      floxuridine (0.48 x 10(-6 )cm/sec) were much higher than that of 5-FU (0.038 x
      10(-6) cm/sec). MDCK cells stably transfected with the human oligopeptide
      transporter PEPT1 (MDCK/hPEPT1) exhibited enhanced cell growth inhibition in the
      presence of the prodrugs. This prodrug strategy offers great potential, not only
      for increased drug absorption but also for improved tumor selectivity and drug
      efficacy.

PMID- 18719517
TI  - Phenolic compounds in field horsetail (Equisetum arvense L.) as natural
      antioxidants.
AB  - In this paper, the study of antioxidant activity and phenolic composition of
      three different extracts (EtOAc, n-BuOH and H(2)O) of field horsetail (Equisetum
      arvense L.) is presented. The antioxidant activity has been evaluated measuring
      the total reducing power (expressed by Ascorbate Equivalent Antioxidant Capacity 
      AEAC), inhibition of lipid peroxidation, and free radical scavenging capacity
      (RSC) towards 2,2-diphenyl-1-picrylhydrazyl (DPPH radical) and nitric oxide (NO),
      respectively. In addition, the total flavonoid content (TFC) and phenolic
      constituents of each extract have been determined. The results obtained show that
      the highest RSC regarding both DPPH and NO radicals is expressed by EtOAc extract
      (EC(50)=2.37 microg/mL and EC(50)=90.07 microg/mL, respectively), and the lowest
      by H(2)O extract (EC(50)=37.2 microg/mL and EC(50)>333.33 microg/mL,
      respectively). n-BuOH extract showed the highest total reducing power (AEAC=13.40
      microg/mL). Differences in the phenolic composition of examined extracts are
      found comparing the HPLC chemical profiles. Although, isoquercitrin is the main
      flavonoid in both EtOAc and n-BuOH extracts, a considerable amount of di-E
      caffeoyl-meso-tartaric acid was presented in the n-BuOH extract. In H(2)O extract
      high content of phenolic acids and low percentage of flavonoids were detected.

PMID- 18719518
TI  - Simplexidine, a 4-alkylpyridinium alkaloid from the Caribbean sponge Plakortis
      simplex.
AB  - Chemical analysis of the secondary metabolites of the Caribbean sponge Plakortis
      simplex, a source of many bioactive compounds, showed the presence of the new
      metabolite simplexidine (4), belonging to the extremely rare class of 4-alkyl
      pyridinium alkaloids. The structural characterization of this molecule, based on
      spectroscopic methods, is reported.

PMID- 18719519
TI  - Facile synthesis of oleanolic acid monoglycosides and diglycosides.
AB  - Oleanolic acid and its glycosides are important natural products, possessing
      various attractive biological activities such as antitumor, antivirus and anti
      inflammatory properties. In the present work, fifteen oleanolic acid saponins
      bearing various saccharide moieties, including 3-monoglycoside, 28-monoglycoside
      and 3,28-diglycoside, were easily synthesized in high yields. Benzyl was chosen
      as the protective group for the COOH(28) group, instead of commonly used methyl
      and allyl, to avoid difficulties in the final deprotection. Alkali-promoted
      condensation of the carboxylic acid with bromo-glycosides was found to be more
      efficient in the synthesis of 28-glycosides. Two approaches were investigated and
      proved practicable in the preparation of 3,28- diglycosides. This method is
      suitable for preparing oleanolic acid glycosides with structural diversity for
      extensive biological evaluation and structure-activity relationship study, and it
      also apply new idea for the corresponding synthetic methods to the glycoside
      derivatives of other triterpenoid.

PMID- 18719520
TI  - Synthesis and antiproliferative activities of 5-azacytidine analogues in human
      leukemia cells.
AB  - Twenty-six 5-azacytidine analogues have been synthesized, including 4-amino- 6
      alkyl-1-pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 1a-j, 6-amino-4
      alkyl/aryl-1- pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 2a-f and 4-amino-6
      alkyl-1,3,5-triazin-2- yl-1-thio-pyranosides/ribofuranosides 3a-j. The
      antiproliferative activities of these synthetic analogues were investigated in
      human leukemia HL-60 cells. Ribofuranosyl S-nucleoside 3a, a bioisostere of 5
      azacytidine, had a similar antiproliferative ability as that of the latter.
      Introduction of a methyl at the 6 position of 5-azacytidine and/or replacement of
      the ribofuranosyl moiety with pyranosyl sugars or disaccharides significantly
      decreased the antiproliferative activities of the 5-azacytidine derivatives.
      Several compounds with the replacement of pyranosyl sugars enhanced all-trans
      retinoic acid-induced differentiation ability in human leukemia HL-60 cells.

PMID- 18719521
TI  - Synthesis and antimicrobial activity of some new pyrazole, fused pyrazolo[3,4-d]
      pyrimidine and pyrazolo[4,3-e][1,2,4]-triazolo[1,5-c]pyrimidine derivatives.
AB  - Hydrazonyl bromides 2a,b reacted with active methylene compounds
      (dibenzoylmethane, acetylacetone, ethyl acetoacetate, phenacyl cyanide,
      acetoacetanilide, ethyl cyanoacetate, cyanoacetamide and malononitrile) to afford
      the corresponding 1,3,4,5- tetrasubstituted pyrazole derivatives 5-12a,b.
      Reaction of 12a,b with formamide, formic acid and triethyl orthoformate give the
      pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4- d]pyrimidin-4(3H)one and 5
      ethoxymethylene-aminopyrazole-4-carbo-nitrile derivatives 13-15a,b, respectively.
      Compounds 15 a,b reacted with benzhydrazide and hydrazine hydrate to afford
      pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine and [4-iminopyrazolo- [3,4
      d]pyrimidin-5-yl]amine derivatives 16 a,b and 17 a,b. Reactions of compounds 17
      a,b with triethyl orthoformate and carbon disulfide give the corresponding
      pyrazolo[4,3-e]- [1,2,4]triazolo[1,5-c]pyrimidine derivatives 18a,b and 19 a,b,
      respectively.

PMID- 18719522
TI  - HPLC-ESI-MS/MS of imidazole alkaloids in Pilocarpus microphyllus.
AB  - Pilocarpine, an important imidazole alkaloid, is extracted from the leaves of
      Pilocarpus microphyllus (Rutaceae), known in Brazil as jaborandi and used mainly
      for the treatment of glaucoma. Jaborandi leaves also contain other imidazole
      alkaloids, whose pharmacological and physiological properties are unknown, and
      whose biosynthetic pathways are under investigation. In the present study, a HPLC
      method coupled with ESI-MS(n) was developed for their qualitative and
      quantitative analysis. This method permits the chromatographic separation of the
      imidazole alkaloids found in extracts of jaborandi, as well as the MS/MS analysis
      of the individual compounds. Thus two samples: leaves of P. microphyllus and a
      paste that is left over after the industrial extraction of pilocarpine; were
      compared. The paste was found to contain significant amounts of pilocarpine and
      other imidazole alkaloids, but had a slightly different alkaloid profile than the
      leaf extract. The method is suitable for the routine analysis of samples
      containing these alkaloids, as well as for the separation and identification of
      known and novel alkaloids from this family, and may be applied to further studies
      of the biosynthetic pathway of pilocarpine in P. microphyllus.

PMID- 18719523
TI  - Aliskiren/hydrochlorothiazide (Tekturna HCT) for hypertension.

PMID- 18719524
TI  - A new rotavirus vaccine.

PMID- 18719525
TI  - Ezetimibe revisited.

PMID- 18719526
TI  - Drugs for tobacco dependence.

PMID- 18719527
TI  - Abstracts of the 2nd International Symposium on Pheochromocytoma, 17-20 September
      2008, Queens' College Cambridge, United Kingdom.

PMID- 18719530
TI  - Magnetic cells for cancer therapy: adopting magnets for cell-based cancer
      therapies.

PMID- 18719536
TI  - Scandalous behaviour.

PMID- 18719538
TI  - A case for nurture.

PMID- 18719537
TI  - Case not closed.

PMID- 18719548
TI  - A biophysicist marvels at the idea of grabbing microscopic particles with light
      by tweaking its phase.

PMID- 18719551
TI  - Whatever floats your boat.

PMID- 18719550
TI  - Unproven stem-cell therapy ban.

PMID- 18719552
TI  - Bell Labs bottoms out.

PMID- 18719560
TI  - Volcanology: Fire and life.

PMID- 18719561
TI  - Neuroscience: The great squid hunt.

PMID- 18719562
TI  - IVF: stars may have to consider the risk of stolen parenthood.

PMID- 18719563
TI  - IVF: tight regulation may not be suitable for all cultures.

PMID- 18719564
TI  - A possible way out of the impact-factor game.

PMID- 18719566
TI  - Micromanaging ideas risks impeding flow of potential benefits.

PMID- 18719565
TI  - Open debate could slow flu vaccine production.

PMID- 18719568
TI  - Innovation policy: not just a jumbo shrimp.

PMID- 18719573
TI  - Developmental biology: Neither fat nor flesh.

PMID- 18719574
TI  - Chemistry: Precious little catalyst.

PMID- 18719575
TI  - Physiology: Mutant flies lack magnetic sense.

PMID- 18719577
TI  - Materials science: A metal left spinning.

PMID- 18719578
TI  - Biogeochemistry: Who lives in the sea floor?

PMID- 18719579
TI  - Archaeology: An oasis in time.

PMID- 18719580
TI  - Obituary: Yoji Totsuka (1942-2008).

PMID- 18719581
TI  - The Trichoplax genome and the nature of placozoans.
AB  - As arguably the simplest free-living animals, placozoans may represent a
      primitive metazoan form, yet their biology is poorly understood. Here we report
      the sequencing and analysis of the approximately 98 million base pair nuclear
      genome of the placozoan Trichoplax adhaerens. Whole-genome phylogenetic analysis
      suggests that placozoans belong to a 'eumetazoan' clade that includes cnidarians
      and bilaterians, with sponges as the earliest diverging animals. The compact
      genome shows conserved gene content, gene structure and synteny in relation to
      the human and other complex eumetazoan genomes. Despite the apparent cellular and
      organismal simplicity of Trichoplax, its genome encodes a rich array of
      transcription factor and signalling pathway genes that are typically associated
      with diverse cell types and developmental processes in eumetazoans, motivating
      further searches for cryptic cellular complexity and/or as yet unobserved life
      history stages.

PMID- 18719582
TI  - PRDM16 controls a brown fat/skeletal muscle switch.
AB  - Brown fat can increase energy expenditure and protect against obesity through a
      specialized program of uncoupled respiration. Here we show by in vivo fate
      mapping that brown, but not white, fat cells arise from precursors that express
      Myf5, a gene previously thought to be expressed only in the myogenic lineage. We
      also demonstrate that the transcriptional regulator PRDM16 (PRD1-BF1-RIZ1
      homologous domain containing 16) controls a bidirectional cell fate switch
      between skeletal myoblasts and brown fat cells. Loss of PRDM16 from brown fat
      precursors causes a loss of brown fat characteristics and promotes muscle
      differentiation. Conversely, ectopic expression of PRDM16 in myoblasts induces
      their differentiation into brown fat cells. PRDM16 stimulates brown adipogenesis
      by binding to PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) and
      activating its transcriptional function. Finally, Prdm16-deficient brown fat
      displays an abnormal morphology, reduced thermogenic gene expression and elevated
      expression of muscle-specific genes. Taken together, these data indicate that
      PRDM16 specifies the brown fat lineage from a progenitor that expresses myoblast
      markers and is not involved in white adipogenesis.

PMID- 18719583
TI  - Magnetic support of the optical emission line filaments in NGC 1275.
AB  - The giant elliptical galaxy NGC 1275, at the centre of the Perseus cluster, is
      surrounded by a well-known giant nebulosity of emission-line filaments, which are
      plausibly in excess of 10(8) years old. The filaments are dragged out from the
      centre of the galaxy by radio-emitting 'bubbles' rising buoyantly in the hot
      intracluster gas, before later falling back. They act as markers of the feedback
      process by which energy is transferred from the central massive black hole to the
      surrounding gas. The mechanism by which the filaments are stabilized against
      tidal shear and dissipation into the surrounding extremely hot (4 x 10(7) K) gas
      has been unclear. Here we report observations that resolve thread-like structures
      in the filaments. Some threads extend over 6 kpc, yet are only 70 pc wide. We
      conclude that magnetic fields in the threads, in pressure balance with the
      surrounding gas, stabilize the filaments, so allowing a large mass of cold gas to
      accumulate and delay star formation.

PMID- 18719584
TI  - Heterogeneous chemistry in the atmosphere of Mars.
AB  - Hydrogen radicals are produced in the martian atmosphere by the photolysis of
      water vapour and subsequently initiate catalytic cycles that recycle carbon
      dioxide from its photolysis product carbon monoxide. These processes provide a
      qualitative explanation for the stability of the atmosphere of Mars, which
      contains 95 per cent carbon dioxide. Balancing carbon dioxide production and loss
      based on our current understanding of the gas-phase chemistry in the martian
      atmosphere has, however, proven to be difficult. Interactions between gaseous
      chemical species and ice cloud particles have been shown to be key factors in the
      loss of polar ozone observed in the Earth's stratosphere, and may significantly
      perturb the chemistry of the Earth's upper troposphere. Water-ice clouds are also
      commonly observed in the atmosphere of Mars and it has been suggested previously
      that heterogeneous chemistry could have an important impact on the composition of
      the martian atmosphere. Here we use a state-of-the-art general circulation model
      together with new observations of the martian ozone layer to show that model
      simulations that include chemical reactions occurring on ice clouds lead to much
      improved quantitative agreement with observed martian ozone levels in comparison
      with model simulations based on gas-phase chemistry alone. Ozone is readily
      destroyed by hydrogen radicals and is therefore a sensitive tracer of the
      chemistry that regulates the atmosphere of Mars. Our results suggest that
      heterogeneous chemistry on ice clouds plays an important role in controlling the
      stability and composition of the martian atmosphere.

PMID- 18719585
TI  - Doping a semiconductor to create an unconventional metal.
AB  - Landau-Fermi liquid theory, with its pivotal assertion that electrons in metals
      can be simply understood as independent particles with effective masses replacing
      the free electron mass, has been astonishingly successful. This is true despite
      the Coulomb interactions an electron experiences from the host crystal lattice,
      lattice defects and the other approximately 10(22) cm(-3) electrons. An important
      extension to the theory accounts for the behaviour of doped semiconductors.
      Because little in the vast literature on materials contradicts Fermi liquid
      theory and its extensions, exceptions have attracted great attention, and they
      include the high-temperature superconductors, silicon-based field-effect
      transistors that host two-dimensional metals, and certain rare-earth compounds at
      the threshold of magnetism. The origin of the non-Fermi liquid behaviour in all
      of these systems remains controversial. Here we report that an entirely different
      and exceedingly simple class of materials-doped small-bandgap semiconductors near
      a metal-insulator transition-can also display a non-Fermi liquid state.
      Remarkably, a modest magnetic field functions as a switch which restores the
      ordinary disordered Fermi liquid. Our data suggest that we have found a physical
      realization of the only mathematically rigorous route to a non-Fermi liquid,
      namely the 'undercompensated Kondo effect', where there are too few mobile
      electrons to compensate for the spins of unpaired electrons localized on impurity
      atoms.

PMID- 18719586
TI  - Selective oxidation with dioxygen by gold nanoparticle catalysts derived from 55
      atom clusters.
AB  - Supported gold nanoparticles have excited much interest owing to their unusual
      and somewhat unexpected catalytic properties, but the origin of the catalytic
      activity is still not fully understood. Experimental work on gold particles
      supported on a titanium dioxide (110) single-crystal surface has established a
      striking size threshold effect associated with a metal-to-insulator transition,
      with gold particles catalytically active only if their diameters fall below
      approximately 3.5 nm. However, the remarkable catalytic behaviour might also in
      part arise from strong electronic interaction between the gold and the titanium
      dioxide support. In the case of industrially important selective oxidation
      reactions, explanation of the effectiveness of gold nanoparticle catalysts is
      complicated by the need for additives to drive the reaction, and/or the presence
      of strong support interactions and incomplete understanding of their possible
      catalytic role. Here we show that very small gold entities ( approximately 1.4
      nm) derived from 55-atom gold clusters and supported on inert materials are
      efficient and robust catalysts for the selective oxidation of styrene by
      dioxygen. We find a sharp size threshold in catalytic activity, in that particles
      with diameters of approximately 2 nm and above are completely inactive. Our
      observations suggest that catalytic activity arises from the altered electronic
      structure intrinsic to small gold nanoparticles, and that the use of 55-atom gold
      clusters may prove a viable route to the synthesis of robust gold catalysts
      suited to practical application.

PMID- 18719587
TI  - Effect of phase transitions on compressional-wave velocities in the Earth's
      mantle.
AB  - The velocities of seismic waves in the Earth are governed by the response of the
      constituent mineral assemblage to perturbations in pressure and stress. The
      effective bulk modulus is significantly lowered if the pressure of the seismic
      wave drives a volume-reducing phase transformation. A comparison between the
      amount of time required by phase transitions to reach equilibrium and the
      sampling period thus becomes crucial in defining the softening and attenuation of
      compressional waves within such a two-phase zone. These phenomena are difficult
      to assess experimentally, however, because data at conditions appropriate to the
      Earth's deep interior are required. Here we present synchrotron-based
      experimental data that demonstrate softening of the bulk modulus within the two
      phase loop of olivine-ringwoodite on a timescale of 100 s. If the amplitude of
      the pressure perturbation and the grain size are scaled to those expected in the
      Earth, the compressional-wave velocities within the discontinuities at 410, 520
      and, possibly, 660 km are likely to be significantly lower than otherwise
      expected. The generalization of these observations to aluminium-controlled phase
      transitions raises the possibility of large velocity perturbations throughout the
      upper 1,000 km of the mantle.

PMID- 18719588
TI  - Self-destructive cooperation mediated by phenotypic noise.
AB  - In many biological examples of cooperation, individuals that cooperate cannot
      benefit from the resulting public good. This is especially clear in cases of self
      destructive cooperation, where individuals die when helping others. If self
      destructive cooperation is genetically encoded, these genes can only be
      maintained if they are expressed by just a fraction of their carriers, whereas
      the other fraction benefits from the public good. One mechanism that can mediate
      this differentiation into two phenotypically different sub-populations is
      phenotypic noise. Here we show that noisy expression of self-destructive
      cooperation can evolve if individuals that have a higher probability for self
      destruction have, on average, access to larger public goods. This situation,
      which we refer to as assortment, can arise if the environment is spatially
      structured. These results provide a new perspective on the significance of
      phenotypic noise in bacterial pathogenesis: it might promote the formation of
      cooperative sub-populations that die while preparing the ground for a successful
      infection. We show experimentally that this model captures essential features of
      Salmonella typhimurium pathogenesis. We conclude that noisily expressed self
      destructive cooperative actions can evolve under conditions of assortment, that
      self-destructive cooperation is a plausible biological function of phenotypic
      noise, and that self-destructive cooperation mediated by phenotypic noise could
      be important in bacterial pathogenesis.

PMID- 18719591
TI  - AMP-activated protein kinase in obesity: metabolic node and beyond--introduction.

PMID- 18719592
TI  - Role of 5'AMP-activated protein kinase in skeletal muscle.
AB  - 5'AMP-activated protein kinase (AMPK) is recognized as an important intracellular
      energy sensor, shutting down energy-consuming processes and turning on energy
      generating processes. Discovery of target proteins of AMPK has dramatically
      increased in the past 10 years. Historically, AMPK was first shown to regulate
      fatty acid and cholesterol synthesis, but is now hypothesized to take part in the
      regulation of energy/fuel balance not only at the cellular level but also at the
      level of the whole organism. In this brief review we will discuss some of the
      roles of AMPK in skeletal muscle.

PMID- 18719589
TI  - New role of bone morphogenetic protein 7 in brown adipogenesis and energy
      expenditure.
AB  - Adipose tissue is central to the regulation of energy balance. Two functionally
      different types of fat are present in mammals: white adipose tissue, the primary
      site of triglyceride storage, and brown adipose tissue, which is specialized in
      energy expenditure and can counteract obesity. Factors that specify the
      developmental fate and function of white and brown adipose tissue remain poorly
      understood. Here we demonstrate that whereas some members of the family of bone
      morphogenetic proteins (BMPs) support white adipocyte differentiation, BMP7
      singularly promotes differentiation of brown preadipocytes even in the absence of
      the normally required hormonal induction cocktail. BMP7 activates a full program
      of brown adipogenesis including induction of early regulators of brown fat fate
      PRDM16 (PR-domain-containing 16; ref. 4) and PGC-1alpha (peroxisome proliferator
      activated receptor-gamma (PPARgamma) coactivator-1alpha; ref. 5), increased
      expression of the brown-fat-defining marker uncoupling protein 1 (UCP1) and
      adipogenic transcription factors PPARgamma and CCAAT/enhancer-binding proteins
      (C/EBPs), and induction of mitochondrial biogenesis via p38 mitogen-activated
      protein (MAP) kinase-(also known as Mapk14) and PGC-1-dependent pathways.
      Moreover, BMP7 triggers commitment of mesenchymal progenitor cells to a brown
      adipocyte lineage, and implantation of these cells into nude mice results in
      development of adipose tissue containing mostly brown adipocytes. Bmp7 knockout
      embryos show a marked paucity of brown fat and an almost complete absence of
      UCP1. Adenoviral-mediated expression of BMP7 in mice results in a significant
      increase in brown, but not white, fat mass and leads to an increase in energy
      expenditure and a reduction in weight gain. These data reveal an important role
      of BMP7 in promoting brown adipocyte differentiation and thermogenesis in vivo
      and in vitro, and provide a potential new therapeutic approach for the treatment
      of obesity.

PMID- 18719593
TI  - Exercise-induced phospho-proteins in skeletal muscle.
AB  - Efforts to identify exercise-induced signaling events in skeletal muscle have
      been influenced by ground-breaking discoveries in the insulin action field.
      Initial discoveries demonstrating that exercise enhances insulin sensitivity
      raised the possibility that contraction directly modulates insulin receptor
      signaling events. Although the acute effects of exercise on glucose metabolism
      are clearly insulin-independent, the canonical insulin signaling cascade has been
      used as a framework by investigators in an attempt to resolve the mechanisms by
      which muscle contraction governs glucose metabolism. This review focuses on
      recent advances in our understanding of exercise-induced signaling pathways
      governing glucose metabolism in skeletal muscle. Particular emphasis will be
      placed on the characterization of AS160, a novel Akt substrate that plays a role
      in the regulation of glucose transport.

PMID- 18719594
TI  - AMP kinase: heart, cancer and the CNS--view from the chair.

PMID- 18719595
TI  - AMP-activated protein kinase control of energy metabolism in the ischemic heart.
AB  - Myocardial ischemia produces an energy-deficient state in heart muscle, which if
      not corrected can lead to cardiomyocyte death. AMP-activated protein kinase
      (AMPK) is a key kinase that can increase energy production in the ischemic heart.
      During ischemia a rapid activation of AMPK occurs, resulting in an activation of
      both myocardial glucose uptake and glycolysis, as well as an increase in fatty
      acid oxidation. This activation of AMPK has the potential to increase energy
      production, thereby protecting the heart during ischemic stress. However, at
      clinically relevant high levels of fatty acids, ischemia-induced activation of
      AMPK also stimulates fatty acid oxidation during and following ischemia. This can
      contribute to ischemic injury secondary to an inhibition of glucose oxidation,
      which results in a decrease in cardiac efficiency. As a result, AMPK activation
      has the potential to be either beneficial or harmful in the ischemic heart.

PMID- 18719596
TI  - The AMPK signaling cascade in metabolic regulation: view from the chair.

PMID- 18719597
TI  - AMP-activated protein kinase and human cancer: cancer metabolism revisited.
AB  - AMP-activated protein kinase (AMPK) and its upstream kinase, LKB1, act to both
      monitor and restore cellular energy in response to energy depletion. Studied
      extensively in liver and skeletal muscle, AMPK is phosphorylated and activated by
      LKB1 in response to increasing AMP/ATP ratios, which occur in a variety of
      settings including hypoxia, nutrient starvation and redox imbalance. Interest in
      the roles of both AMPK and LKB1 in cancer has grown substantially, following the
      identification of LKB1 as the tumor suppressor gene mutated in the Peutz-Jegher
      familial cancer syndrome. Patients with the Peutz-Jegher syndrome harbor a single
      inactive LKB1 gene, and acquisition of a second inactivating lesion (loss of
      heterozygosity) leads to the development of the cancer in a variety of organs.
      Thus, the loss of AMPK activation is hypothesized to promote the development of
      malignancy. Conversely, pharmacological AMPK activation has recently been shown
      to be cytotoxic to many established human cancer cell lines in vitro and in human
      cancer xenograft and mouse cancer allografts. Previously, changes in cell
      metabolism that accompanied the malignant phenotype have largely been considered
      a consequence of cellular transformation. Now, AMPK and energy metabolism are
      linked to the development and maintenance of the malignant phenotype. These
      findings have led to renewed interest in AMPK and cancer cell metabolism in
      general as potential targets for cancer therapy.

PMID- 18719598
TI  - AMP-activated protein kinase in the brain.
AB  - Since its discovery as an important regulator of fuel utilization in the
      periphery, AMP-activated protein kinase (AMPK) has become a contender for many
      important cell-intrinsic and organismal roles regarding energy balance in the
      central nervous system. The challenge will be to delineate the mechanisms by
      which neuronal AMPK can respond to cellular energy requirements as well as whole
      body energy demands. Thus, under physiological conditions in the brain,
      hypothalamic AMPK responds to changes in energy balance/food intake, whereas
      under pathological conditions, AMPK responds globally in the brain to energy
      challenge. Modulation of fatty acid metabolism affects energy balance in a
      context-specific manner and may provide an insight into other mechanisms for
      selective activation or inhibition of AMPK activity for therapeutic applications.

PMID- 18719599
TI  - Regulation of food intake and energy expenditure by hypothalamic malonyl-CoA.
AB  - Energy balance is monitored by the hypothalamus. Malonyl-CoA, an intermediate in
      fatty acid synthesis, serves as an indicator of energy status in the hypothalamic
      neurons. The cellular malonyl-CoA level is determined by its rate of synthesis,
      catalyzed by acetyl-CoA carboxylase (ACC), and rate of removal, by fatty acid
      synthase (FAS). Malonyl-CoA functions in the hypothalamic neurons that express
      orexigenic and anorexigenic neuropeptides. Inhibitors of FAS, administered
      systemically or intracerebroventricularly to mice, increase hypothalamic malony
      CoA and suppress food intake. Recent evidence suggests that the changes of
      hypothalamic malonyl-CoA during feeding and fasting cycles are caused by changes
      in the phosphorylation state and activity of ACC mediated via 5'-AMP-activated
      protein kinase (AMPK). Stereotactic delivery of a viral malonyl-CoA decarboxylase
      (MCD) vector into the ventral hypothalamus lowers malonyl-CoA and increases food
      intake. Fasting decreases hypothalamic malonyl-CoA and refeeding increases
      hypothalamic malonyl-CoA, to alter feeding behavior in the predicted manner.
      Malonyl-CoA level is under the control of AMP kinase which
      phosphorylates/inactivates ACC. Malonyl-CoA is an inhibitor of carnitine
      palmitoyl-CoA transferase-1 (CPT1), an outer mitochondrial membrane enzyme that
      regulates entry into, and oxidation of fatty acids, by mitochondria. CPT1c, a
      recently discovered, brain-specific enzyme expressed in the hypothalamus, has
      high sequence similarity to liver/muscle CPT1a/b and binds malonyl-CoA, but does
      not catalyze the prototypical reaction. This suggests that CPT1c has a unique
      function or activation mechanism. CPT1c knockout (KO) mice have lower food
      intake, weigh less and have less body fat, consistent with the role as an energy
      sensing malonyl-CoA target. Paradoxically, CPT1c protects against the effects of
      a high-fat diet. CPT1cKO mice exhibit decreased rates of fatty acid oxidation,
      consistent with their increased susceptibility to diet-induced obesity. We
      suggest that CPT1c may be a downstream target of malonyl-CoA that regulates
      energy homeostasis.

PMID- 18719600
TI  - The regulation of AMP-activated protein kinase by upstream kinases.
AB  - AMP-activated protein kinase (AMPK) is the downstream component of a protein
      kinase cascade that plays a major role in maintaining energy homoeostasis. Within
      individual cells, AMPK is activated by a rise in the AMP/ATP ratio that occurs
      following a fall in ATP levels. AMPK is also regulated by the adipokines,
      adiponectin and leptin, hormones that are secreted from adipocytes. AMPK
      regulates a wide range of metabolic pathways, including fatty acid oxidation,
      fatty acid synthesis, glycolysis and gluconeogenesis. In peripheral tissues,
      activation of AMPK leads to responses that are beneficial in counteracting the
      deleterious effects that arise in the metabolic syndrome. Recent studies have
      demonstrated that modulation of AMPK activity in the hypothalamus plays a role in
      feeding. A decrease in hypothalamic AMPK activity is associated with decreased
      feeding, whereas activation of AMPK leads to increased food intake. Furthermore,
      signalling pathways occurring in the hypothalamus lead to changes in AMPK
      activity in peripheral tissues, such as skeletal muscle, via the sympathetic
      nervous system. AMPK, therefore, provides a mechanism for monitoring changes in
      energy metabolism within individual cells and at the level of the whole body.
      Activation of AMPK requires phosphorylation of threonine 172 (Thr-172) within the
      catalytic subunit. Recent studies have shown that both LKB1 and Ca(2+)/calmodulin
      dependent protein kinase kinase-beta (CaMKKbeta) play important roles in
      phosphorylating and activating AMPK. In addition, there is evidence that AMPK can
      be activated by other upstream kinases, although the physiological significance
      of this is not clear at present. This review focuses on the role of LKB1 and
      CaMKKbeta in the regulation of AMPK.

PMID- 18719601
TI  - AMPK: a key regulator of energy balance in the single cell and the whole
      organism.
AB  - The AMP-activated protein kinase (AMPK) system is a key player in regulating
      energy balance at both the cellular and whole-body levels, placing it at centre
      stage in studies of obesity, diabetes and the metabolic syndrome. It is switched
      on in response to metabolic stresses such as muscle contraction or hypoxia, and
      modulated by hormones and cytokines affecting whole-body energy balance such as
      leptin, adiponectin, resistin, ghrelin and cannabinoids. Once activated, it
      switches on catabolic pathways that generate adenosine triphosphate (ATP), while
      switching off ATP-consuming anabolic processes. AMPK exists as heterotrimeric
      complexes comprising a catalytic alpha-subunit and regulatory beta- and gamma
      subunits. Binding of AMP to the gamma-subunit, which is antagonized by high ATP,
      causes activation of the kinase by promoting phosphorylation at threonine (Thr
      172) on the alpha-subunit by the upstream kinase LKB1, allowing the system to act
      as a sensor of cellular energy status. In certain cells, AMPK is activated in
      response to elevation of cytosolic Ca2+ via phosphorylation of Thr-172 by
      calmodulin-dependent kinase kinase-beta (CaMKKbeta). Activation of AMPK, either
      in response to exercise or to pharmacological agents, has considerable potential
      to reverse the metabolic abnormalities associated with type 2 diabetes and the
      metabolic syndrome. Two existing classes of antidiabetic drugs, that is,
      biguanides (for example, metformin) and the thiazolidinediones (for example,
      rosiglitazone), both act (at least in part) by activation of AMPK. Novel drugs
      activating AMPK may also have potential for the treatment of obesity.

PMID- 18719602
TI  - Initial description of the human NLRP3 promoter.
AB  - Mutations in NLRP3 (CIAS1) are identified in a continuum of related inflammatory
      disorders, known as cryopyrinopathies since NLRP3 codes for the protein
      cryopyrin. Approximately 40% of patients with classic presentation lack mutations
      in the coding region of NLRP3 suggesting heterogeneity or epigenetic factors.
      Cryopyrin is a key regulator of proinflammatory cytokine release. Therefore,
      variations in the NLRP3 promoter sequence may have effects on disease state in
      patients with cryopyrinopathies and other inflammatory diseases. In this report,
      we confirmed three 5'-untranslated region splice forms with two separate
      transcriptional start sites, and identified potential promoter regions and six
      new DNA promoter variants. One variant is unique to a mutation negative
      cryopyrinopathy patient and increases in vitro gene expression. Additional
      studies can now be performed to further characterize the NLRP3 promoter and
      sequence variants, which will lead to better understanding of the regulation of
      NLRP3 expression and its role in disease.

PMID- 18719603
TI  - A T-cell-specific CD154 transcriptional enhancer located just upstream of the
      promoter.
AB  - CD154 (CD40-ligand) is a critical immune regulator. CD154 expression is tightly
      regulated and largely restricted to activated CD4 T cells. Using DNase I
      hypersensitivity site (HSS) mapping, we identified two novel HSS mapping to the
      human CD154 promoter element and just upstream. Both HSS were activation
      independent and CD4 T-cell specific. Approximately 350 bp of DNA sequence
      flanking the upstream HSS site was highly conserved between mouse and man, and
      was rich in binding sites for GATA and NFAT proteins. Gel shift and chromatin
      immunoprecipitation assays demonstrated both NFAT1 and the Th2 factor, GATA-3,
      bound this enhancer element in vitro and in vivo, respectively. A PstI/XbaI 345
      bp fragment of this region acted as a transcriptional enhancer of the CD154
      promoter in primary human CD4 T cells. Overexpression of repressor of GATA and a
      dominant negative GATA-3 protein independently inhibited transcription, whereas
      overexpression of wild-type GATA-3 enhanced transcriptional activity, by this
      element in primary CD4 T cells. Moreover, more interleukin-4-producing CD4 T
      cells expressed CD154 following activation than interferon-gamma-producing CD4 T
      cells. Thus, we identified a novel T-cell-specific, GATA-3 responsive, CD154
      transcriptional enhancer, which may contribute to increased propensity of Th2
      cells to express CD154.

PMID- 18719604
TI  - Evolving concepts of pathogenesis in atopic dermatitis and other eczemas.
AB  - The eczemas represent a common and diverse group of inflammatory skin diseases
      whose definitions and pathogenic mechanisms have often been confused and
      controversial. Since the millennium, fresh approaches are providing better
      insight. Research has focused much more upon the epidermis and the very relevant
      signaling pathways that contribute to spongiosis, proliferation, generation of
      proinflammatory factors, and differentiation to form an effective stratum corneum
      barrier. A major step in understanding has come from the solidly confirmed
      association between filaggrin null mutations of ichthyosis vulgaris and atopic
      dermatitis. Similar associations relating to protease and lipid defects have
      highlighted the role of barrier disruption that allows greater access of
      environmental toxins, microbes, and allergens. Animal models are beginning to
      predict mechanisms in which such direct perturbation of keratinocytes may
      initiate inflammation and condition immune responses in irritant contact
      dermatitis and atopic dermatitis. These conceptual shifts are nurturing more
      balanced approaches to understanding eczema and hold the hope for better
      prevention efforts and more specific molecular targeting for therapy.

PMID- 18719605
TI  - An epinephrine-dependent mechanism for the control of UV-induced pigmentation.

PMID- 18719606
TI  - Transglutaminase-3 enzyme: a putative actor in human hair shaft scaffolding?
AB  - The family of transglutaminases (TGase) is known to be involved in terminal
      differentiation processes in the epidermis. These enzymes contribute also to the
      physical resistance and the preservation of the hair follicle structure. Our
      particular interest in hair fiber keratinization led us to focus on the TGase 3,
      exclusively expressed in the hair shaft. To date its function is still to be
      elucidated, thus we have developed a multidisciplinary approach in order to
      define the localization, activity, and substrates of TGase 3. The hair fiber is
      characterized by the expression of specific proteins essentially consisting of
      keratin intermediate filaments and keratin-associated proteins (KAPs), which are
      essential for the formation of a rigid hair shaft through their extensive
      disulfide cross-links. Gel electrophoresis combined with mass spectrometry
      experiments revealed an unexpected protein migration pattern, suggesting the
      existence of covalent interactions other than disulfide bonds. Western blot and
      amino-acid analysis revealed the presence of gamma-glutamyl-epsilon-lysine
      isopeptide linkages that could constitute this second covalent network. Our
      hypothesis is that TGase 3-driven specific isopeptide bonds between intermediate
      filaments and KAPs participate to the progressive scaffolding of the hair shaft.

PMID- 18719607
TI  - Functional analysis of FLT4 mutations associated with Nonne-Milroy lymphedema.

PMID- 18719608
TI  - Chemokines in the pathogenesis of lichenoid tissue reactions.
AB  - Clinical manifestations of lichenoid tissue reactions are heterogenous and
      include the cutaneous lupus erythematosus and lichen planus. Lichenoid tissue
      reactions are characterized by epidermal basal-cell damage and a variable
      subepithelial inflammatory infiltrate including cytotoxic T(H)1 cells and
      plasmacytoid dendritic cells. Here, we summarize the current knowledge of the
      role of chemokines in the pathophysiology of lichenoid tissue reactions and
      propose mechanisms by which recruitment and local activation of cytotoxic T(H)1
      cells and plasmacytoid dendritic cells may result in initiation and amplification
      of lichen planus and cutaneous lupus erythematosus.

PMID- 18719609
TI  - Markers to evaluate the quality and self-renewing potential of engineered human
      skin substitutes in vitro and after transplantation.
AB  - We screened a series of antibodies for their exclusive binding to the human hair
      follicle bulge. In a second step these antibodies were to be used to identify
      basal keratinocytes and potential epithelial stem cells in the human epidermis
      and in engineered skin substitutes. Of all the antibodies screened, we identified
      only one, designated C8/144B, that exclusively recognized the hair follicle
      bulge. However, C8/144B-binding cells were never detected in the human epidermal
      stratum basale. In the bulge C8/144B-binding cells gave rise to cytokeratin 19
      positive cells, which were also tracked in the outer root sheath between bulge
      and the hair follicle matrix. Remarkably, cytokeratin 19-expressing cells were
      never detected in the hair follicle infundibulum. Yet, cytokeratin 19-expressing
      keratinocytes were found in the epidermal stratum basale of normal skin as a
      subpopulation of cytokeratin 15-positive (not C8/144B-positive) basal
      keratinocytes. Cytokeratin 19/cytokeratin 15-positive keratinocytes decreased
      significantly with age. We suggest that cytokeratin 19-expressing cells represent
      a subpopulation of basal keratinocytes in neonates and young children (up to 1.5
      years) that is particularly adapted to the lateral expansion of growing skin. Our
      data show that cytokeratin 19 in combination with cytokeratin 15 is an important
      marker to routinely monitor epidermal homeostasis and (at least indirectly) the
      self-renewing potential of engineered skin.

PMID- 18719610
TI  - Myeloid differentiation factor 88 regulates basal and UV-induced expressions of
      IL-6 and MMP-1 in human epidermal keratinocytes.
AB  - Myeloid differentiation factor 88 (MyD88) is known as an adaptor protein for the
      Toll-like receptor (TLR) family and participates in signal transduction by
      binding to the cytoplasmic Toll/IL-1 receptor (TIR) domains of activated TLR. In
      this study, we demonstrated that expression of MyD88 is increased in photoaged
      skin compared with intrinsic aged human skin of the same elderly individuals, and
      that acute UV irradiation increases MyD88 expression in human skin in vivo. To
      investigate the effects of these high levels of MyD88 in photoaged skin and
      acutely UV-irradiated skin, human epidermal keratinocytes were infected with
      adenovirus expressing wild-type (MyD88wt), dominant-positive (MyD88DeltaC), and
      dominant-negative (MyD88DeltaN) MyD88 forms. Overexpression of MyD88wt and
      MyD88DeltaC, but not of MyD88DeltaN, increased the basal expressions of IL-6 and
      matrix metalloproteinase-1 (MMP-1) in human epidermal keratinocytes. Moreover,
      overexpression of MyD88DeltaN prevented UV-induced expressions of IL-6 and MMP-1
      by inhibiting UV-induced activation of NF-kappaB and activating protein-1. These
      results suggest that MyD88 is important in IL-6 and MMP-1 expressions in both
      acutely UV-irradiated skin and in chronically sun-exposed human skin.

PMID- 18719611
TI  - Candidate housekeeping genes require evaluation before their selection for
      studies of human epidermal keratinocytes.

PMID- 18719612
TI  - Characterization of coordinated immediate responses by p16INK4A and p53 pathways
      in UVB-irradiated human skin cells.
AB  - While the precise mechanisms of melanoma development are unknown, recent in vivo
      studies have revealed that the p16(Ink4a)/Rb pathway is disrupted in
      melanomagenesis. Here, we characterize the role of p16/Rb in coordinating the
      early events in UVB-irradiated skin. Foreskins and melanoma cell cultures were
      irradiated with low and high acute UVB doses and examined for cell-cycle- and
      apoptosis-associated genes. In melanoma cells, low UVB dose upregulated p16, p53,
      and p21 expression levels in Malme-3M, and high UVB dose accentuated the
      expression of p53 and p21(Cip1/Waf1), in particular; however, in SkMel-28 cells
      only p16 expression was upregulated in response to UV irradiation. In HaCaT
      cells, high UVB dose caused dramatic increase in p53 expression followed by
      upregulation of p21(Cip1/Waf1) and Bax, and downregulation of Bcl-2 leading to
      apoptosis. In HaCaT cells, reinstatement of p16 pathway restored cell-cycle
      arrest in response to low dose. Foreskin organ culture experiments confirmed our
      in vitro cell results. These data indicate that the p53 and p16 pathways respond
      independently to UVB insult. The p16 pathway is favored at low doses and results
      in cell-cycle arrest; the p53 pathway is more responsive to higher doses and
      induces apoptosis depending on p53 mutation status.

PMID- 18719615
TI  - Serum uric acid level in primary hypertension among Chinese
      nonagenarians/centenarians.
AB  - Epidemiologic studies suggest an independent positive association of elevated
      serum uric acid with essential hypertension. However, to date, limited
      information is available in the old population. In the present study, we included
      832 unrelated Chinese nonagenarians/centenarians (269 men and 563 women; ranged
      in age from 90 to 108 years (mean, 94.6+/-4.0)). The mean serum uric acid level
      was 320 micromol l(-1) (standard deviation 87 micromol l(-1)). After adjustment
      for age, body mass index, waist-to-hip ratio, smoking habits, tea habits, alcohol
      consumption, fasting plasma glucose, plasma lipids and serum creatinine, the odds
      ratio comparing the highest with lowest quartile of serum uric acid were 0.67
      (95% confidence interval (CI), 0.33-1.21) and 1.36 (95% CI, 0.88-2.22) in men and
      women, respectively. When compared with normotensive subjects, we did not observe
      statistical higher serum uric acid levels in subjects with hypertension. In
      summary, we found that serum uric acid level is not directly correlated with
      hypertension among Chinese nonagenarians/centenarians.

PMID- 18719616
TI  - Etiology of common childhood acute lymphoblastic leukemia: the adrenal
      hypothesis.
AB  - The pattern of infections in the first years of life modulates our immune system,
      and a low incidence of infections has been linked to an increased risk of common
      childhood acute lymphoblastic leukemia (ALL). We here present a new
      interpretation of these observations--the adrenal hypothesis--that proposes that
      the risk of childhood ALL is reduced when early childhood infections induce
      qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis
      that increase plasma cortisol levels. This may directly eliminate leukemic cells
      as well as preleukemic cells for the ALL subsets that dominate in the first 5-7
      years of life and may furthermore suppress the Th1-dominated proinflammatory
      response to infections, and thus lower the proliferative stress on pre-existing
      preleukemic cells.

PMID- 18719614
TI  - Lysogenic virus-host interactions predominate at deep-sea diffuse-flow
      hydrothermal vents.
AB  - The consequences of viral infection within microbial communities are dependent on
      the nature of the viral life cycle. Among the possible outcomes is the
      substantial influence of temperate viruses on the phenotypes of lysogenic
      prokaryotes through various forms of genetic exchange. To date, no marine
      microbial ecosystem has consistently shown a predisposition for containing
      significant numbers of inducible temperate viruses. Here, we show that deep-sea
      diffuse-flow hydrothermal vent waters display a consistently high incidence of
      lysogenic hosts and harbor substantial populations of temperate viruses. Genetic
      fingerprinting and initial metagenomic analyses indicate that temperate viruses
      in vent waters appear to be a less diverse subset of the larger virioplankton
      community and that these viral populations contain an extraordinarily high
      frequency of novel genes. Thus, it appears likely that temperate viruses are key
      players in the ecology of prokaryotes within the extreme geothermal ecosystems of
      the deep sea.

PMID- 18719617
TI  - Molecular detection of AML1-MTG8-positive cells in peripheral blood from a
      patient with isolated extramedullary relapse of t(8;21) acute myeloid leukemia.

PMID- 18719618
TI  - Secretion of angiogenic proteins by human multipotent mesenchymal stromal cells
      and their clinical potential in the treatment of avascular osteonecrosis.
AB  - Osteonecrosis is a frequent complication after treatment for childhood leukemia
      and other steroid-based therapies. The success rate of core decompression surgery
      is limited. Therefore, we evaluated relevant biological characteristics of human
      multipotent mesenchymal stromal cells (MSCs) in vitro. MSCs cultured under low
      oxygen tensions showed decreased proliferation and differentiation into bone.
      However, these MSCs secreted significant amounts of vascular endothelial-derived
      factor in the presence of interferon-gamma. These in vitro results with potential
      effects on neovascularization and bone regeneration as well as findings in animal
      models prompted us to treat five patients with steroid-induced osteonecrosis of
      the femur by core decompression surgery and instillation of expanded autologous
      MSCs. Within 3 weeks of culture, sufficient numbers of MSCs were generated using
      animal protein-free culture conditions. No chromosomal aberrations were detected
      by matrix-based comparative genomic hybridization. Application of MSCs during
      core decompression was feasible and safe. Median follow-up is 16 months and the
      patients in this pilot study reported clinical improvement. Formation of
      mineralized bone in the osteonecrotic cavity was proven by computed tomography.
      Taken together, MSCs display biological properties that may add to the efficiency
      of surgical treatment in osteonecrosis and should be evaluated in larger patient
      cohorts.

PMID- 18719619
TI  - Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine
      during breastfeeding: a case-control study.
AB  - A large number of women receive codeine for obstetric pain while breastfeeding.
      Following a case of fatal opioid poisoning in a breastfed neonate whose codeine
      prescribed mother was a CYP2D6 ultrarapid metabolizer (UM), we examined
      characteristics of mothers and infants with or without signs of central nervous
      system (CNS) depression following codeine exposure while breastfeeding in a case
      control study. Mothers of symptomatic infants (n = 17) consumed a mean 59% higher
      codeine dose than mothers of asymptomatic infants (n = 55) (1.62 (0.79) mg/kg/day
      vs. 1.02 (0.54) mg/kg/day; P = 0.004). There was 71% concordance between maternal
      and neonatal CNS depression. Two mothers whose infants exhibited severe neonatal
      toxicity were CYP2D6 UMs and of the UGT2B7*2/*2 genotype. There may be a dose
      response relationship between maternal codeine use and neonatal toxicity, and
      strong concordance between maternal-infant CNS depressive symptoms. Breastfed
      infants of mothers who are CYP2D6 UMs combined with the UGT2B7*2/*2 are at
      increased risk of potentially life-threatening CNS depression.

PMID- 18719620
TI  - A data mining approach to in vivo classification of psychopharmacological drugs.
AB  - Data mining is a powerful bioinformatics strategy that has been successfully
      applied in vitro to screen for gene-expression profiles predicting toxicological
      or carcinogenic response ('class predictors'). In this report we used a data
      mining algorithm named Pattern Array (PA) in vivo to analyze mouse open-field
      behavior and characterize the psychopharmacological effects of three drug classes
      -psychomotor stimulant, opioid, and psychotomimetic. PA represents rodent
      movement with approximately 100,000 complex patterns, defined as multiple
      combinations of several ethologically relevant variables, and mines them for
      those that maximize any effect of interest, such as the difference between drug
      classes. We show that PA can discover behavioral predictors of all three drug
      classes, thus developing a reliable drug-classification scheme in small group
      sizes. The discovered predictors showed orderly dose dependency despite being
      explicitly mined only for class differences, with the high doses scoring 4-10
      standard deviations from the vehicle group. Furthermore, these predictors
      correctly classified in a dose-dependent manner four 'unknown' drugs (ie that
      were not used in the training process), and scored a mixture of a psychomotor
      stimulant and an opioid as being intermediate between these two classes. The
      isolated behaviors were highly heritable (h(2)>50%) and replicable as determined
      in 10 inbred strains across three laboratories. PA can in principle be applied
      for mining behaviors predicting additional properties, such as within-class
      differences between drugs and within-drug dose-response, all of which can be
      measured automatically in a single session per animal in an open-field arena,
      suggesting a high potential as a tool in psychotherapeutic drug discovery.

PMID- 18719622
TI  - Pulse wave analysis is a reproducible technique for measuring central blood
      pressure during hemodynamic perturbations induced by exercise.
AB  - BACKGROUND: Central blood pressure (BP) and markers of wave reflection
      (augmentation index; AIx) measured by radial tonometry have prognostic value
      independent from brachial BP. The measurement of the central waveform is
      increasingly used during altered hemodynamics, including exercise, but
      reliability of the test has not been reported under changed loading conditions.
      This study aimed to test the technique's reproducibility during major hemodynamic
      perturbations induced by exercise. METHODS: Radial waveforms were recorded
      (SphygmoCor) in 28 healthy subjects (aged 53 +/- 11 years) at rest, during
      submaximal exercise (cycling at 50, 60, and 70% of maximal age-predicted heart
      rate (HR)) and immediately after maximal treadmill exercise on two occasions
      separated by 9 +/- 5 days. Data were compared between testing days. Waveforms
      were calibrated with brachial BP measured using a mercury sphygmomanometer. Pulse
      pressure amplification (PPAmp) was defined as the ratio of brachial to central
      pulse pressure. RESULTS: There was very good reproducibility between visits at
      all exercise intensities for all waveform measures, including AIx, central pulse
      pressure, and PPAmp (intraclass correlations at 50% exercise were 0.93, 0.89, and
      0.89, respectively; P < 0.001). The mean difference between tests at this
      intensity was 0 +/- 4% for AIx, 4 +/- 6 mm Hg for central pulse pressure, and 
      0.02 +/- 0.09 for PPAmp. There were no significant differences between visits for
      HR, PPAmp, or AIx at rest or with exercise (P > 0.05 for all). CONCLUSIONS:
      Radial tonometry is a reproducible technique for measurement of central waveform
      indices during perturbations induced by exercise. It should, therefore, be
      suitable for use in intervention studies in which hemodynamics are altered.

PMID- 18719621
TI  - A history of corticosterone exposure regulates fear extinction and cortical NR2B,
      GluR2/3, and BDNF.
AB  - A history of exposure to stressors may be a predisposing factor for developing
      posttraumatic stress disorder (PTSD) after trauma. Extinction of conditioned fear
      appears to be impaired in PTSD, but the consequences of prior stress or excess
      glucocorticoid exposure for extinction learning are not known. We report that
      prior chronic exposure to the stress hormone, corticosterone (CORT), decreases
      endogenous CORT secretion upon context reexposure and impairs extinction after
      contextual fear conditioning in rats, while leaving fear memory acquisition and
      expression intact. Posttraining administration of the glucocorticoid receptor
      (GR) antagonist, RU38486, partially mimicked prior CORT exposure effects on
      freezing during fear extinction training. Extinction of conditioned fear is an
      active learning process thought to involve glutamatergic targets--including
      specific NMDA and AMPA receptor subunits--in the ventromedial prefrontal cortex
      (vmPFC), which includes the prelimbic, infralimbic, and medial orbitofrontal
      cortices. After CORT exposure, decreases in the NMDA receptor NR2B subunit and
      AMPA receptor subunits, GluR2/3, as well as brain-derived neurotrophic factor,
      were detected in cortical regions, but not dorsal hippocampus (CA1). Receptor
      subunit expression levels in the vmPFC correlated with freezing during training.
      In addition, prior CORT selectively decreased sucrose preference, consistent with
      established models of anhedonia and with blunted affect in PTSD. Together, these
      data suggest a cellular mechanism by which chronically elevated glucocorticoid
      exposure--as may be experienced during repeated exposure to stressors--interferes
      with the neural systems that modulate behavioral flexibility and may thereby
      contribute to psychopathological fear states.

PMID- 18719629
TI  - Psychiatric and cardiovascular comorbidities in patients with diabetes mellitus
      starting antiobesity drugs.
AB  - The aim of the study was to assess whether the baseline risk of psychiatric and
      cardiovascular disease in patients with diabetes mellitus differs between those
      starting to use antiobesity drugs and those not starting to use these drugs. A
      retrospective nested case-control study within the General Practice Research
      Database (1987-2002) was done. The cohort included all patients with diabetes
      mellitus (n = 141,164). Information on patient characteristics (general,
      cardiovascular, and psychiatric characteristics) was extracted from the medical
      records. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated. A total of 511 patients starting to use antiobesity drugs (cases) and
      3,065 controls were included in the study cohort. Starters were younger and more
      frequently female. Of the starters, 91.8% did not receive any dietary advice
      before starting treatment. Depression (in the year before index date) was
      associated with the use of antiobesity drugs (OR 2.2; 95% CI 1.7-2.8), as was
      anxiety (OR 1.6; 95% CI 1.1-2.4). Of the cases, 25.2% had multiple cardiovascular
      risk factors (>4) compared to 19.0% of the controls. The baseline risk for
      psychiatric disorders and cardiovascular disease was found to be higher in
      patients with diabetes mellitus starting to use antiobesity drugs compared to
      patients with diabetes mellitus not starting such treatment.

PMID- 18719630
TI  - The interaction of childhood height and childhood BMI in the prediction of young
      adult BMI.
AB  - The purpose of this study was to examine the interaction of childhood height and
      childhood BMI in the prediction of young adult BMI. The 2,802 subjects in this
      study were from the Child and Adolescent Trial for Cardiovascular Health (CATCH).
      The subjects' heights and weights were measured in 3rd grade (mean age 8.7 years)
      and again in 12th grade (mean age 18.3 years). The associations and interactions
      between height (cm) and BMI (kg/m(2)) were assessed using mixed linear regression
      models with adult BMI as the dependent variable. We found a significant
      interaction between childhood height and childhood BMI in the prediction of adult
      BMI (P < 0.0001). Stratification by Centers for Disease Control and Prevention
      (CDC) reference quintiles revealed that a positive association between childhood
      height and adult BMI existed only for those subjects in the top quintile of
      childhood BMI, within whom predicted adult BMI ranged from 27.5 (95% confidence
      interval = 26.4-28.6) for those in the shortest height quintile to 30.2 (95%
      confidence interval = 29.7-30.6) for those in the highest height quintile. Among
      children with high BMI levels, those who were taller, as compared to those who
      were shorter, had significantly higher young adult BMI levels. This pattern seems
      primarily due to the positive association of childhood height and childhood BMI.
      Clinicians should recognize the risk of excess body weight in young adulthood for
      all children who have a high BMI, and pay special attention to those who are
      tall, because their childhood height will not protect them from subsequent weight
      gain and elevated BMI.

PMID- 18719631
TI  - Variation in the bitter-taste receptor gene TAS2R38, and adiposity in a
      genetically isolated population in Southern Italy.
AB  - OBJECTIVE: Variation in the bitter-taste receptor gene, TAS2R38 confers the
      ability to taste 6-n-propylthiouracil (PROP). The objective of this study was to
      relate TAS2R38 haplotypes and PROP-tasting phenotypes to adiposity in a
      genetically isolated population. We hypothesized that the nontaster phenotype
      would be associated with higher BMI and waist circumference (WC) in females, and
      that dietary restraint would mediate this relationship. METHODS AND PROCEDURES:
      Participants were 540 healthy inhabitants of the genetically isolated village of
      Carlantino in southern Italy who were 15-89 years of age at the time of the
      study. Haplotype analyses were performed and PROP tasting was assessed using a
      filter paper method. Height, weight, and WC were measured and restrained eating
      was assessed using a brief questionnaire. RESULTS: Nontaster females had higher
      BMI and WC than females who were phenotypic tasters, and this relationship was
      specific to females with low dietary restraint. Regression analysis showed that
      BMI declined by 1.7 units across taster groups in females when the model included
      the PROP by restraint interaction. PROP phenotype was not significantly
      associated with WC in the regression models. Polymorphisms in TAS2R38 were not
      associated with BMI or WC in females. Neither TAS2R38 haplotype nor PROP
      phenotype was strongly related to BMI or WC in males. DISCUSSION: These data
      support previous findings of a relation between the nontaster phenotype and
      higher BMI in females that is modified by dietary restraint. Assessment of PROP
      phenotypes might provide unique information about adiposity that is not captured
      by haplotype analysis alone.

PMID- 18719632
TI  - Effect of a cellulose-containing weight-loss supplement on gastric emptying and
      sensory functions.
AB  - CM3, a highly cross-linked cellulose in capsule form, expands in the stomach to a
      size several fold of its original volume. It is purported to induce a prolonged
      feeling of satiation and a delay in gastric emptying, thus promoting weight loss.
      We examined whether CM3 delays gastric emptying (using the stable isotope (13)C
      octanoic breath test) and whether it influences subjective feelings of appetite
      sensations (using visual analog scales, VASs). We performed a double-blind
      randomized placebo-controlled crossover trial in 19 moderately obese but
      otherwise healthy subjects (mean age 55 +/- 9 years, BMI 31.1 +/- 4.6 kg/m(2)).
      The subjects were treated with six capsules of CM3 or matching placebo 30 min
      before a standardized solid meal. Breath collection and VASs were performed over
      4 h every 15 min and 30 min, respectively. Half-excretion time of (13)CO(2) in
      breath, indicating gastric emptying half time, was the primary outcome parameter.
      The study was powered to detect a change in gastric emptying of 20-30 min. Mean
      (13)CO(2) half-excretion time changed from 2.3 +/- 0.4 to 2.4 +/- 0.33 h (mean
      difference +6 min, 95% confidence interval (CI) -3 to +15 min; P = 0.17).
      Appetite sensations (hunger, satiation, fullness, prospective food consumption,
      desire to eat something sweet, salty, savory, or fatty) changed over time during
      the course of the postprandial phase but were not influenced by CM3 (repeated
      measures ANOVA). In obese subjects, acute administration of the weight-loss
      supplement CM3 does not delay gastric emptying and does not influence subjective
      appetite sensations.

PMID- 18719633
TI  - High-fat meal-induced changes in the duodenum mucosa transcriptome.
AB  - In order to identify the potential peripheral signals of appetite and satiety
      from duodenum, we have performed a transcriptomic study in the mucosa after high
      fat (HF) and low-fat (LF) meal ingestion. After fasting, one group of mice was
      killed and the others were fed ad libitum with HF or LF diet, and killed 30 min,
      1 h, and 3 h after the beginning of the meal. The duodenum mucosa was sampled,
      and the serial analysis of gene expression (SAGE) method was performed. The mRNA
      regulations were confirmed by real-time PCR. Energy, protein, and fat intakes
      were higher in the HF than in the LF group. Gene expression profile revealed 118
      characterized or partially characterized differentially expressed transcripts.
      The HF meal delayed the expressions of peptidases compared to the LF groups. Most
      of mRNAs related to fat absorption, including apolipoprotein A-IV (Apoa4), were
      decreased in HF1h group, whereas plasma triglyceride (TG) levels were comparable
      between HF and LF groups. Noteworthy, these downregulations were concomitant to a
      break in fat intake 1 h after HF meal. At the same time, the HF meal induced
      transcripts related to cell growth and organization, whereas transcripts involved
      in cell defense were repressed. Moreover, we have identified fat-responsive
      transcripts. This study has characterized the molecular responses of duodenum
      mucosa after HF or LF meal ingestion. Characterization of novel fat-specific
      candidates whose relations with feeding behavior have never been reported may
      contribute to the development of new therapeutic targets for appetite and satiety
      controls.

PMID- 18719634
TI  - Will all Americans become overweight or obese? estimating the progression and
      cost of the US obesity epidemic.
AB  - We projected future prevalence and BMI distribution based on national survey data
      (National Health and Nutrition Examination Study) collected between 1970s and
      2004. Future obesity-related health-care costs for adults were estimated using
      projected prevalence, Census population projections, and published national
      estimates of per capita excess health-care costs of obesity/overweight. The
      objective was to illustrate potential burden of obesity prevalence and health
      care costs of obesity and overweight in the United States that would occur if
      current trends continue. Overweight and obesity prevalence have increased
      steadily among all US population groups, but with notable differences between
      groups in annual increase rates. The increase (percentage points) in obesity and
      overweight in adults was faster than in children (0.77 vs. 0.46-0.49), and in
      women than in men (0.91 vs. 0.65). If these trends continue, by 2030, 86.3%
      adults will be overweight or obese; and 51.1%, obese. Black women (96.9%) and
      Mexican-American men (91.1%) would be the most affected. By 2048, all American
      adults would become overweight or obese, while black women will reach that state
      by 2034. In children, the prevalence of overweight (BMI >/= 95th percentile, 30%)
      will nearly double by 2030. Total health-care costs attributable to
      obesity/overweight would double every decade to 860.7-956.9 billion US dollars by
      2030, accounting for 16-18% of total US health-care costs. We continue to move
      away from the Healthy People 2010 objectives. Timely, dramatic, and effective
      development and implementation of corrective programs/policies are needed to
      avoid the otherwise inevitable health and societal consequences implied by our
      projections .

PMID- 18719640
TI  - Efficiency of intermittent exercise on adiposity and fatty liver in rats fed with
      high-fat diet.
AB  - OBJECTIVE: This study aimed to examine and compare the effects of continuous or
      intermittent exercises on adiposity and fatty liver in rats fed with high-fat
      diet. METHODS AND PROCEDURES: Wistar rats were divided according to diet
      composition-chow diet (C) or high-fat diet (H)-and kinds of exercise-sedentary
      (S), continuous (CE), or intermittent (IE) exercises. The CE group swam 90
      min/day, and the IE group swam 3 x 30 min/day (at 4-h intervals between
      sessions); both groups exercised 5 days/week during 8 weeks. Body weight and food
      intake were recorded daily. Lipogenesis rate in vivo was determined by the
      incorporation of (3)H(2)O into saponified lipids in retroperitoneal (RET),
      epididymal (EPI), and visceral (VIS) white adipose tissues, brown adipose tissue
      (BAT), liver (L), and gastrocnemius muscle (GAST) using the gravimetric method.
      Total cholesterol, high-density lipoprotein (HDL)-cholesterol, and
      triacylglycerol (TG) were analyzed. RESULTS: The major finding of this study is
      that IE was more efficient than CE in reducing the adverse effects of high-fat
      diet and sedentarism. There was an improvement in the lipid profile and a
      reduction in food intake, body weight gain, visceral and central adiposity, and
      fatty liver, contributing to the control of obesity and other comorbidities,
      including nonalcoholic fat liver diseases. DISCUSSION: Earlier studies have
      discussed the effects of diet consumption on adiposity and their relation to
      chronic diseases and obesity. This study discusses the effects of high-fat diet
      consumption and the different kinds of exercise on weight gain, adiposity, fatty
      liver, and lipid profile in rats. The results may depend on the exercise, time of
      each session, age, gender, and experimental period.

PMID- 18719641
TI  - Conjugated linoleic acid-induced fat loss dependence on Delta6-desaturase or
      cyclooxygenase.
AB  - OBJECTIVE: To determine whether conjugated linoleic acid (CLA)-induced body fat
      loss is dependent upon metabolism of CLA by Delta6-desaturase, cyclooxygenase, or
      lipoxygenase. METHODS AND PROCEDURES: Mice were fed diets with or without CLA and
      inhibitors to either Delta6-desaturase (SC-26196), cyclooxygenase (aspirin), or
      lipoxygenase (nordihydroguaiaretic acid (NDGA)) for 2 weeks. Body fat percent,
      lean mass, fat pad weights, liver weight, and fatty acid concentrations were
      determined. A Delta6-desaturase index was calculated, and adipose tissue
      prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) concentrations were
      determined to confirm enzyme inhibition. RESULTS: Inhibition of Delta6-desaturase
      and cyclooxygenase were confirmed. CLA caused a loss of body fat (P < 0.001). The
      body fat loss was blocked (P = 0.08) by the Delta6-desaturase inhibitor at a dose
      that decreased (P < 0.05) the calculated index. Aspirin and NDGA had no effect on
      body fat and did not interact with CLA. DISCUSSION: Inhibition of Delta6
      desaturase prevented CLA from being able to cause a body fat loss. Therefore, a
      desaturated metabolite of CLA appears to be involved in the CLA antiobesity
      effect. This effect of CLA does not seem dependent upon cyclooxygenase. Because
      lipoxygenase activity was not blocked by NDGA, we cannot draw conclusions about
      its importance in mediating the antiobesity effect of CLA.

PMID- 18719642
TI  - Myocardial ischemic-reperfusion injury in a rat model of metabolic syndrome.
AB  - Hearts of NaCl-induced hypertensive-glucose intolerant (HGI) rats develop reduced
      infarcts after ischemia-reperfusion injury (IRI) than their hypertensive (H)
      counterparts. Because high intake of saturated fat is a major risk factor for
      ischemic heart disease, we tested the hypothesis that chronic (18 weeks)
      consumption of a high saturated fat diet increases susceptibility to IRI, an
      effect more marked in the HGI rats than in the H rats. The fat-fed H (HFAT) rat
      displayed significantly higher body weight and plasma leptin content compared to
      the H, HGI, or fat-fed HGI (HGIFAT) rats which all showed similar values. In
      contrast, plasma triglyceride concentration was significantly higher in the
      HGIFAT rat than in the other three groups. Plasma insulin concentration was
      similar in the two H groups but higher than that of the two HGI groups. Compared
      to the H rat, the HGI rat was markedly glucose intolerant, with fat feeding
      causing comparable worsening of glucose intolerance in each group. The HGIFAT
      rats displayed a reduction in baseline myocardial contractility and relaxation
      and a higher end-diastolic pressure compared to the other three groups. Infarct
      size was significantly lower in the HGI rats than in the H rats. Although fat
      feeding did not affect infarct size of the H rat, it worsened that of the HGIFAT
      rat thereby abrogating the differential that existed between the H and HGI rats.
      In conclusion, excess fat feeding impairs myocardial function of HGI rats and
      increases their susceptibility to IRI. These findings are of relevance to the
      metabolic syndrome that manifests as a cluster of insulin resistance,
      dyslipidemia, and systemic hypertension.

PMID- 18719643
TI  - Ordered stratification to reduce heterogeneity in linkage to diabetes-related
      quantitative traits.
AB  - Phenotypic heterogeneity complicates detection of genomic loci predisposing to
      type 2 diabetes, potentially obscuring or unmasking specific loci. We conducted
      ordered-subsets linkage analyses (OSAs) for diabetes-related quantitative traits
      (fasting insulin and glucose, hemoglobin A1c (HbA1c), and 28-year-time-averaged
      fasting plasma glucose (FPG)) from 330 families of the Framingham Offspring
      Study. We calculated mean BMI, waist circumference (WC), and a diabetes "age-of
      onset score" for each family. We constructed subsets by adding one family at a
      time in increasing (lean family to obese) or decreasing (obese to lean) adiposity
      order, or increasing or decreasing propensity to develop diabetes at a younger
      age, with the OSA LOD reported as the maximum LOD observed in any subset.
      Permutation P values tested the hypothesis that phenotypic ordering showed
      stronger linkage than random ordering. On chromosome 1, ordering by increasing
      family mean WC increased linkage to time-averaged FPG at 256 cM from LOD = 2.4 to
      3.5 (permuted P = 0.02) and to HbA1c at 180 cM from LOD = 2.0 to 3.3 (P = 0.01).
      On chromosome 19, ordering by decreasing WC increased linkage to fasting insulin
      at 68 cM from LOD = 2.7 to 4.6 (P = 0.002), and ordering by decreasing propensity
      to develop diabetes at a young age increased linkage to fasting insulin at 73 cM
      from LOD = 2.7 to 4.0 (P = 0.046). We conclude that chromosomes 1 and 19 could
      harbor adiposity-interacting diabetes susceptibility genes. Such interactions
      might also influence trait-locus associations and may be useful to consider in
      diabetes genome-wide association studies.

PMID- 18719644
TI  - Is obesity associated with anemia of chronic disease? A population-based study.
AB  - Obesity is characterized by chronic, low-grade, systemic inflammation, which, in
      turn, has been associated with anemia of chronic disease. We hypothesized that
      obesity may be associated with the features of anemia of chronic disease,
      including low hemoglobin concentration, low serum iron and transferrin saturation
      (TS), and elevated serum ferritin. We compared normal-weight to overweight and
      obese adult participants of the third National Health and Nutrition Examination
      Survey with respect to hemoglobin concentration and levels of serum iron, TS, and
      ferritin. Measured BMI was used to categorize participants into normal weight
      (BMI < 25 kg/m(2), n = 6,059), overweight (BMI 25 to <30 kg/m(2), n = 5,108),
      mildly obese (BMI 30 to <35 kg/m(2), n = 2,366), moderately obese (BMI 35 to <40
      kg/m(2), n = 850), and severely obese (BMI > or = 40 kg/m(2), n = 465). After
      adjustment for age, gender, menstruation, race/ethnicity, education, alcohol
      consumption, smoking, blood donation, and dietary iron intake, serum ferritin was
      progressively higher with increasing BMI category, whereas serum iron and TS were
      progressively lower. However, compared to normal-weight persons, those in all
      other higher BMI categories did not have a significant change in hemoglobin
      concentration after adjustment for the above-mentioned confounders. Overweight
      and obesity were associated with changes in serum iron, TS, and ferritin that
      would be expected to occur in the setting of chronic, systemic inflammation.
      However, overweight and obese persons were not more likely to be anemic compared
      with normal-weight persons.

PMID- 18719646
TI  - Postpubertal development of total and abdominal percentage body fat: an 8-year
      longitudinal study.
AB  - The aim of the present study was to describe postpubertal changes in total and
      abdominal adiposity in young men and the relation to changes in physical activity
      (PA). The study included 107 white men with a mean age of 17.1 +/- 1.7 years at
      baseline. Total percentage body fat (%BF) and abdominal percentage body fat
      (abd%BF) were measured at baseline and after a mean time of 28, 68, and 92 months
      using dual-energy X-ray absorptiometry (DXA). PA (h/week) was assessed at each
      visit by questionnaire. Over the study period, significant increases of 7.8 +/-
      5.5%BF and 9.0 +/- 5.6 abd%BF were observed. Subjects who were active athletes
      throughout the study (n = 24), or nonathletes not changing their level of PA
      during follow-up (n = 27) increased 5.7 +/- 3.2 and 8.1 +/- 6.7%BF, respectively.
      Athletes who quit organized training during follow-up period (n = 56) increased
      by 8.7 +/- 4.9%BF. In the total cohort, the average annual gains in BMI, %BF, and
      abd%BF were 0.4 kg/m(2), 0.9%BF, and 1.1abd%BF (all P < 0.0001), respectively.
      Adjustment for changes in PA altered the coefficient magnitudes only marginally.
      Changes in PA were, however, significantly and inversely associated with changes
      in %BF and abd%BF (P = 0.005 and P = 0.02, respectively), but were not
      significantly associated with BMI development (P = 0.15). In summary, our results
      indicate that the natural course of adiposity development in postpubertal men is
      characterized by adiposity gains. The influence of PA on especially abd%BF may
      influence the future risk of cardiovascular disease.

PMID- 18719645
TI  - Effects of ritonavir on adipocyte gene expression: evidence for a stress-related
      response.
AB  - To understand the molecular mechanisms underlying the development of dyslipidemia
      and lipodystrophy that occurs after administration of aspartic acid protease
      inhibitors, we examined transcriptional profiles using cDNA microarrays in 3T3-L1
      adipocytes exposed to 10 micromol/l ritonavir for 2-21 days. The expression
      levels of approximately 12,000 transcripts were assessed using the MgU74Av2 mouse
      microarray chip. Ritonavir altered gene expression of inflammatory cytokines,
      stress response genes localized to endoplasmic reticulum, oxidative stress genes,
      apoptosis-related genes, and expression of genes involved in cell adhesion and
      extracellular matrix remodeling. Microarray analysis also identified a novel gene
      downregulated by ritonavir, Cidea, whose expression levels may affect free-fatty
      acid metabolism. These changes suggest a unique, stress-related pattern in
      adipocytes induced by chronic exposure to the protease inhibitor, ritonavir.

PMID- 18719647
TI  - Child obesity can be reduced with vigorous activity rather than restriction of
      energy intake.

PMID- 18719648
TI  - In vivo and in vitro glucocorticoid sensitivity in obese people with cushingoid
      appearance.
AB  - Clinical similarities between Cushing's syndrome and obesity/metabolic syndrome
      have led to speculation of a role for glucocorticoids (GCs) in the
      etiopathogenesis of obesity. People with idiopathic obesity have normal
      circulating cortisol concentrations. However, there may be considerable
      interindividual variation in GC sensitivity. The objective of this study was to
      determine whether enhanced GC sensitivity in the absence of GC excess was a
      characteristic of obese people with cushingoid features. We studied 12 obese
      subjects with cushingoid features in the absence of Cushing's syndrome and six
      slim control participants. Data recorded included BMI, waist-to-hip ratio, blood
      pressure, glucose and insulin response to 75 g oral glucose challenge, and low
      dose (0.25 mg) overnight dexamethasone (DEX) suppression test (ODST-0.25 mg). To
      study GC-sensitivity in vitro, we performed dose-response studies of DEX-induced
      suppression of interleukin-6 (IL-6) secretion in skin fibroblast cultures. Seven
      obese subjects were normosensitive and five subjects hypersensitive to GCs in
      vitro. ODST-0.25 mg resulted in a median suppression of cortisol from baseline of
      32% in normosensitive and 60% in hypersensitive obese subjects (P < 0.004). No
      other clinical or biochemical measures were discriminatory between these two
      groups. These data from two independent measures of GC sensitivity suggest that
      enhanced GC sensitivity may characterize a substantial proportion of obese people
      with cushingoid appearance.

PMID- 18719649
TI  - Association of ADIPOR2 with liver function tests in type 2 diabetic subjects.
AB  - OBJECTIVE: Adiponectin protects against liver dysfunction in insulin-resistant
      states such as obesity and type 2 diabetes (T2DM), but the role of adiponectin
      receptors in this disorder is largely unknown. We studied whether common single
      nucleotide polymorphisms (SNPs) in ADIPOR1 and ADIPOR2 are associated with liver
      function tests (LFTs) in human subjects with various degrees of insulin
      resistance. METHODS AND PROCEDURES: Serum alanine (ALT) and aspartate (AST)
      aminotransferases, homeostasis model assessment of insulin resistance (HOMA-IR), 
      8503 G/A (rs6666089) and +5843 C/T (rs1342387) SNPs in ADIPOR1, -64,241 T/G
      (rs1029629) and +33447 C/T (rs1044471) SNPs in ADIPOR2 were assessed in 700 white
      subjects from a population-based study. RESULTS: In nondiabetic subjects, the at
      risk alleles for the common -64,241 T/G and +33447 C/T SNPs in ADIPOR2 were
      associated with increased circulating adiponectin (P < 0.05 to P < 0.005), but
      not with LFT. Conversely, in T2DM subjects (who are at risk for liver
      dysfunction), the same alleles were associated with increased serum ALT and AST
      (P < 0.05 to P < 0.0001), but not with circulating adiponectin. No significant
      associations with these parameters were evident for the common -8503 G/A and
      +5843 C/T SNPs in ADIPOR1. In a replication study, the -64,241 T/G and +33447 C/T
      SNPs in ADIPOR2 were associated with ALT and AST (P < 0.05 to P < 0.0001) in
      pooled obese and T2DM subjects. DISCUSSION: Common SNPs in ADIPOR2 are associated
      with LFT in T2DM subjects, which suggests a possible role of this receptor in
      liver dysfunction associated with insulin resistance.

PMID- 18719650
TI  - Low resting energy expenditure in Asians can be attributed to body composition.
AB  - OBJECTIVE: To compare resting energy expenditure (REE) between Asians and whites
      after adjusting for fat-free mass measured with a two- or more-compartment model.
      METHODS AND PROCEDURES: Participants were 10 white men (28 +/- 3 years), 10 Asian
      men (30 +/- 4 years), 10 white women (22 +/- 4 years), and 11 Asian women (31 +/-
      7 years). REE was measured with a ventilated hood system under strictly
      controlled conditions. Body composition was measured with a two-compartment model
      based on body mass (BM) and body volume (hydrodensitometry), a three-compartment
      model adding total body water (TBW) (deuterium dilution), and a four-compartment
      model incorporating bone mass (dual-energy X-ray absorptiometry (DXA)) as well.
      Lean BM in the trunk and in the extremities was assessed with DXA. All
      measurements were performed at Maastricht University. Measurements on Asian
      subjects were performed within 3 months after their arrival in the Netherlands.
      RESULTS: Absolute REE was lower in Asians (5.87 +/- 0.91 MJ/day) than in whites
      (7.00 +/- 1.11 MJ/day). There was no significant difference in REE between the
      two races after adjustment for fat-free mass. DISCUSSION: There were no
      significant differences in REE between Asians and whites after adjustment for
      differences in body composition based on a two- or more-compartment model.

PMID- 18719651
TI  - Age- and gender-specific BMI in terms of the lowest mortality in Japanese general
      population.
AB  - OBJECTIVE: The primary purposes of our study were to establish age- and gender
      specific BMIs in terms of lowest mortality (risk nadir BMIs) for the Japanese
      population, and to then compare those to (i) BMIs for whites as determined by
      similar studies and to (ii) the official BMI guidelines. METHODS AND PROCEDURES:
      A total of 32,060 men and 61,916 women aged 40-79 years underwent health check
      ups in Ibaraki prefecture, Japan, in 1993 and were followed through 2003. To
      determine the age- and gender-specific risk nadir BMIs, coefficients and the
      lowest point from a quadratic model with transformed BMI were calculated by a Cox
      proportional hazard model. This included the quadratic term of 1/BMI and adjusted
      values (age, alcohol intake, and smoking status). RESULTS: For both age and both
      gender categories, the relationship between all-cause mortality risk and BMI
      categories are illustrated as U-shaped curves. The risk nadir BMIs for men in the
      age groups of 40-59 and 60-79 years were 23.4 and 25.3 kg/m(2), respectively.
      Similarly, in women, the risk nadir BMIs were 21.6 and 23.4 kg/m(2),
      respectively. DISCUSSION: Among the general Japanese population, the risk nadir
      BMI for the age group of 60-79 years was higher compared to the age group of 40
      59 years, which was similar to the study for whites, and the age-dependent risk
      nadir BMI differed from the official guidelines criteria. Our findings underscore
      the importance of weight control following appropriate indicators of body weight
      according to age.

PMID- 18719652
TI  - Maternal treatment with oleoyl-estrone induces resistance to lipid accrual in
      their descendants.
AB  - OBJECTIVE: To determine whether treatment of rat dams with oleoyl-estrone (OE)
      has an effect on the offspring's long-term response to diet restriction during
      lactation. METHODS AND PROCEDURES: Control, OE-treated, and diet-restricted dams
      were treated up to day 15 of lactation. Changes in food intake and body weight
      were recorded for dams and their pups. After weaning, pups received a 4-week
      standard diet followed by a 4-week period of high-fat diet. Lipid, protein, and
      energy content of pups plus energy intake and efficiency. Serum metabolites
      (glucose, urea, and cholesterol) and serum hormones (adiponectin, leptin,
      insulin, and sexual hormones). RESULTS: Neither pups from dams in the OE-treated
      nor in the diet-restricted group showed significant changes in weight, though
      these two groups ingested 79% of food ingested by controls. At weaning, the pups
      from OE-treated rats were smaller than those of the control or diet-restricted
      groups. These pups maintained the differences in size and lipid content during
      the 4-week standard-diet period, whereas pups from diet-restricted dams showed a
      sharp decrease in their lipid content. During the 4 weeks of high-fat diet, the
      male offspring from OE-treated dams increased the difference in lipid content in
      relation to the pups from control dams whereas in females the differences
      decreased. Female offspring from diet-restricted dams showed the most marked
      changes in metabolite and hormone levels in relation to controls. DISCUSSION:
      Treatment of lactating dams with OE programs the metabolic response of their
      offspring to resist the challenge of a high-fat diet that would lead to obesity
      in adulthood.

PMID- 18719654
TI  - Weight regain and health-related quality of life in postmenopausal women.
AB  - Weight loss improves health-related quality of life (HRQoL). However, regain
      after loss is common; little is known about the impact of weight regain on HRQoL
      in postmenopausal women. Woman on the Move through Activity and Nutrition (WOMAN)
      is a randomized lifestyle intervention trial of diet, physical activity, and
      weight loss in 508 postmenopausal women aged 52-62 years. This analysis focused
      on the women who lost > or =5 lb during the initial phase of the study, baseline
      to 6 months (n = 248). This cohort was divided into three groups based on
      subsequent weight change between 6 and 18 months: weight loss (WL; > or =5 lb
      loss), weight stable (WS; <+/-5 lb change), and weight regain (WR; > or =5 lb
      gain). HRQoL was measured at baseline, 6, and 18 months using the Short Form-36.
      Of the 248 women studied, 51 (21%) continued to lose weight after initial weight
      loss, while 127 (51%) maintained a stable weight, and 70 (28%) regained weight.
      Between baseline and 6 months, women in WR group had decreased mental health and
      social-functioning scores, while the WL and WS groups improved in these
      subscales. Between baseline and 18 months, energy improved most significantly in
      those with continued weight loss (P = 0.0003). Weight loss was correlated with a
      small to moderate improvement in perceived general health and energy, which was
      reversed by weight gain. Further study is needed to investigate the impact of a
      decline in mental health and social functioning on future weight regain.

PMID- 18719653
TI  - Weight-specific health-related quality of life in adolescents with extreme
      obesity.
AB  - The objectives of this multisite study were to: (i) examine differences by gender
      and race on generic and weight- specific health-related quality of life (HRQOL)
      in adolescents with extreme obesity (BMI > or = 40 kg/m(2)) and (ii) explore
      HRQOL differences based on treatment pursued (behavioral vs. bariatric surgery).
      Study participants included 145 obese adolescents (mean age = 15.3 years; 68%
      female; 46% black; mean BMI = 50.6) referred to pediatric weight management
      programs. Participants completed generic (PedsQL) and weight-specific (Impact of
      Weight on Quality of Life-Kids (IWQOL-Kids)) HRQOL measures. Generic and weight
      specific measures indicated global (e.g., all domains) HRQOL impairment and
      significant differences by race. Physical, emotional, and social scores of the
      PedsQL (Ps < 0.01) and the physical comfort and body esteem scores of the IWQOL
      Kids (Ps < 0.001) were significantly higher for black compared to white
      adolescents with extreme obesity. Extremely obese adolescents pursuing bariatric
      surgery reported similar HRQOL to adolescents pursuing behavioral treatment (n =
      30 matched pairs). HRQOL did not differ for extremely obese adolescents based on
      type of treatment sought, but race/ethnicity should be considered when
      characterizing these youth. Although racial differences in adolescent body
      image/esteem have been reported, it is unknown why black adolescents with extreme
      obesity would report less impact of weight on their physical functioning.
      Overall, these data suggest that HRQOL is not homogenous in adolescents with
      extreme obesity.

PMID- 18719658
TI  - Gender differences in the relationship of ENPP1/PC-1 variants to obesity in a
      Turkish population.
AB  - The ectoenzyme ENPP1 (also termed membrane glycoprotein PC-1 or ENPP1/PC-1) is an
      inhibitor of insulin-induced activation of the insulin receptor. There is
      evidence from previous studies that coding variants of ENPP1/PC-1 (K121Q) are
      associated with type 2 diabetes (T2D) and obesity. Studies in the general Turkish
      population have demonstrated: unique plasma lipid characteristics, a high
      prevalence of cardiovascular risk factors, and an increased prevalence of obesity
      and T2D. We investigated, therefore, the association of ENPP1/PC-1 variants with
      obesity and T2D in Turkish individuals. The TaqMan allelic discrimination assay
      was used for genotyping the relationship of ENPP1/PC-1 variants to obesity and
      T2D in a genetic association study of 1,553 genotyped, randomly selected subjects
      from the Turkish Heart Study. The K121Q (rs1044498) variant and other previously
      reported variants (rs997509, rs1799774, rs1044548, rs11964389, rs7754561) were
      analyzed. In this cohort, the minor allele frequency (MAF) of the K121Q variant
      was associated with obesity in male, but not in female subjects (male, odds ratio
      1.64, 95% confidence interval 1.004-2.698, P = 0.048; female, odds ratio 1.003,
      95% confidence interval 0.684-1.471, P = ns). In addition, the previously
      reported ENPP1/PC-1 "risk haplotype" (Q (rs1044498), delT (rs1799774), and G
      (rs7754561) alleles) was found to be associated with obesity in male, but not in
      female, subjects (P = 0.035). In contrast, there was no association of either the
      K121Q variant or the ENPP1/PC-1 haplotype with T2D. We find evidence that
      variants of ENPP1/PC-1 are associated with obesity in the male Turkish
      population; thus, these variants may contribute to the development of the obesity
      in these individuals.

PMID- 18719659
TI  - Adiposity measures and oxidative stress among police officers.
AB  - Our objective was to investigate associations between adiposity measures (BMI,
      waist circumference, waist-to-hip ratio, waist-to-height ratio, and abdominal
      height) and biomarkers of oxidative stress (glutathione (GSH), GSH peroxidase
      (GSH-Px), vitamin C, thiobarbituric acid reactive substances (TBARS), and trolox
      equivalent antioxidant capacity (TEAC)) among police officers. This cross
      sectional study included randomly selected police officers (43 policewomen; 67
      policemen) from Buffalo, New York. Adiposity measures were performed using
      standardized methods. Biomarkers were measured on fasting blood specimens. An
      oxidative stress score (OSS) was created as a composite of the biomarkers. ANOVAs
      were used to compare mean levels of biomarkers across tertiles of the adiposity
      measures. Officers were 26- to 61-years old. GSH was inversely associated with
      waist circumference (trend P = 0.030) and waist-to-hip ratio (trend P = 0.026).
      GSH-Px was inversely associated with BMI (trend P = 0.004) and with waist-to
      height ratio (trend P = 0.017). No associations were observed for TEAC, TBARS, or
      OSS with any adiposity measure. Significant interactions were observed by
      physical activity status for GSH with waist circumference and waist-to-hip ratio
      and for vitamin C with waist circumference, waist-to-hip and waist-to-height
      ratios. The above associations were inversely related only among officers who
      reported engaging in physical activity. Inverse associations were observed for
      BMI and waist circumference with GSH, but only among women; the interaction with
      gender was significant. Larger indices of adiposity were associated with
      increased levels of oxidative stress and decreased levels of antioxidant defense.

PMID- 18719660
TI  - Role of estrogen receptor-alpha and -beta in regulating leptin expression in 3T3
      L1 adipocytes.
AB  - We investigated the effects of the estrogen receptor-alpha (ERalpha) and -beta
      (ERbeta) in the regulation of leptin, resistin, and adiponectin expression in 3T3
      L1 adipocytes. Mature adipocytes were exposed to estradiol (E2), ERalpha agonist
      (PPT (4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol)), ERbeta agonist
      (DPN (2,3-bis(4-Hydroxyphenyl)-propionitrile)), E2 with ERalpha antagonist (MPP
      (1,3-Bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole
      dihydrochloride)), and E2 with ERbeta antagonist (R,R-THC ((R,R)-5,11-diethyl
      5,6,11,12-tetrahydro-2,8-chrysenediol)) at different concentrations. To clarify
      the expression and regulation of adipokines by ER subtypes, total RNA was
      extracted from cells and measured using quantitative PCR. Western blot analysis
      was performed to evaluate the protein expression of adipokines, ERalpha, and
      ERbeta. The leptin expression was significantly increased in the cells treated
      with high concentrations (10(-5) and 10(-6) mol/l) of the PPT (P < 0.01, P <
      0.05). By contrast, the leptin expression decreased in a dose-dependent manner in
      the MPP-treated groups (P < 0.05). High concentrations (10(-5) mol/l) of R,R-THC
      with E2 (10(-7) mol/l) caused a significant increase of the leptin expression (P
      < 0.01). The leptin mRNA levels were positively correlated with the ERalpha mRNA
      levels (r = 0.584, P < 0.01) and negatively correlated with the ERbeta mRNA
      levels (r = -0.236, P = 0.03) in the adipocytes. The ratio of the ERalpha to
      ERbeta mRNA levels in the adipocytes was significantly associated with leptin
      mRNA levels (r = 0.454, P < 0.01). ERalpha induced leptin expression and ERbeta
      inhibited its expression in 3T3-L1 adipocytes. The ratio of the ERalpha-to-ERbeta
      expression in 3T3-L1 adipocytes may be an important potential regulatory factor
      in leptin expression.

PMID- 18719661
TI  - Glucose-dependent insulinotropic polypeptide (GIP) stimulates transepithelial
      glucose transport.
AB  - The purpose of this study was to characterize the effects of glucose-dependent
      insulinotropic peptide (GIP) on small intestinal glucose transport in vitro.
      Stripped proximal jejunum from fasted mice was mounted in Ussing chambers. The
      serosal side was bathed in Regular Ringer solution containing 5 mmol/l glucose,
      and the mucosal side, with solution containing 10 mmol/l 3-O-methyl glucose
      (3OMG). Intercellular cyclic adenosine monophosphate (cAMP), mucosa-to-serosa
      fluxes of 3OMG (J(ms)(3OMG)), and short-circuit current (I(SC)) were measured in
      the presence and absence of GIP. GIP increased cAMP by 2.5-fold in isolated
      enterocytes, consistent with a direct effect of GIP on these epithelial cells.
      GIP also increased I(SC) and J(ms)(3OMG) by 68 and 53%, respectively, indicating
      that the increase in J(ms)(3OMG) was primarily electrogenic, with a small
      electroneutral component. The stimulatory effect of GIP on J(ms)(3OMG) was
      concentration dependent. In addition, 1,000 nmol/l and 10 nmol/l GIP increased
      J(ms)(3OMG) by 70 and 30% over control, respectively, consistent with receptor
      activation. Phlorizin (20 mumol/l), an inhibitor of Na(+)-glucose cotransporter
      (SGLT-1), abolished the increase in I(SC) and decreased J(ms)(3OMG) by
      approximately 65%. These results indicate that stimulation of SGLT-1 activity by
      GIP partially accounts for the increase in J(ms)(30MG). These studies are the
      first to demonstrate direct stimulation of intestinal glucose transport by GIP
      independent of its insulinotropic properties. GIP stimulates cellular
      accumulation of cAMP and thereby upregulates glucose transport. The GIP-induced
      increase in glucose transport appears to be mediated, at least in part, by SGLT
      1.

PMID- 18719662
TI  - Weight loss maintenance in a population-based sample of German adults.
AB  - The objective of this study was to investigate the prevalence of weight loss
      maintenance in a population-based sample of the German adult population. German
      adults were recruited based on the random digital-dialing methodology. Using
      computer-assisted telephone interviewing, weight loss maintenance was assessed,
      defined as having intentionally lost at least 10% from maximum weight and having
      maintained it for at least 1 year at the time of the survey. A total of 2,095
      noninstitutionalized adults were randomly selected from all parts of Germany and
      the data of 957 respondents were included into the analysis. Of those who were at
      least overweight (BMI >or= 25 kg/m(2)) at their maximum weight, 17.7% reported
      having maintained a current weight loss of >or=10% of their maximum weight for at
      least 1 year. Among participants who reported a maximum weight in the obese range
      (BMI >or= 30 kg/m(2)), 29.7% reported successful 1-year weight loss maintenance.
      Among at least overweight participants, being younger and female, and having a
      higher maximum BMI were significant predictors of successful 1-year weight loss
      maintenance. The results suggest that successful weight loss maintenance is not
      uncommon in the general population, particularly in formerly obese participants.
      More should be learned about the strategies that successful weight maintainers
      use to avoid regaining weight.

PMID- 18719664
TI  - The FTO gene is associated with adulthood obesity in the Mexican population.
AB  - Common polymorphisms in the fat mass and obesity-associated gene (FTO) have shown
      strong association with obesity in several populations. In the present study, we
      explored the association of FTO gene polymorphisms with obesity and other
      biochemical parameters in the Mexican population. We also assessed FTO gene
      expression levels in adipose tissue of obese and nonobese individuals. The study
      comprised 788 unrelated Mexican-Mestizo individuals and 31 subcutaneous fat
      tissue biopsies from lean and obese women. FTO single-nucleotide polymorphisms
      (SNPs) rs9939609, rs1421085, and rs17817449 were associated with obesity,
      particularly with class III obesity, under both additive and dominant models (P =
      0.0000004 and 0.000008, respectively). These associations remained significant
      after adjusting for admixture (P = 0.000003 and 0.00009, respectively). Moreover,
      risk alleles showed a nominal association with lower insulin levels and
      homeostasis model assessment of B-cell function (HOMA-B), and with higher
      homeostasis model assessment of insulin sensitivity (HOMA-S) only in nonobese
      individuals (P (dom) = 0.031, 0.023, and 0.049, respectively). FTO mRNA levels
      were significantly higher in subcutaneous fat tissue of class III obese
      individuals than in lean individuals (P = 0.043). Risk alleles were significantly
      associated with higher FTO expression in the class III obesity group (P = 0.047).
      In conclusion, FTO is a major risk factor for obesity (particularly class III) in
      the Mexican-Mestizo population, and is upregulated in subcutaneous fat tissue of
      obese individuals.

PMID- 18719665
TI  - Emerging adulthood and college-aged youth: an overlooked age for weight-related
      behavior change.

PMID- 18719666
TI  - High-throughput screening of mouse knockout lines identifies true lean and obese
      phenotypes.
AB  - We developed a high-throughput approach to knockout (KO) and phenotype mouse
      orthologs of the 5,000 potential drug targets in the human genome. As part of the
      phenotypic screen, dual-energy X-ray absorptiometry (DXA) technology estimates
      body-fat stores in eight KO and four wild-type (WT) littermate chow-fed mice from
      each line. Normalized % body fat (nBF) (mean KO % body fat/mean WT littermate %
      body fat) values from the first 2322 lines with viable KO mice at 14 weeks of age
      showed a normal distribution. We chose to determine how well this screen
      identifies body-fat phenotypes by selecting 13 of these 2322 KO lines to serve as
      benchmarks based on their published lean or obese phenotype on a chow diet. The
      nBF values for the eight benchmark KO lines with a lean phenotype were > or =1
      s.d. below the mean for seven (perilipin, SCD1, CB1, MCH1R, PTP1B, GPAT1,
      PIP5K2B) but close to the mean for NPY Y4R. The nBF values for the five benchmark
      KO lines with an obese phenotype were >2 s.d. above the mean for four (MC4R,
      MC3R, BRS3, translin) but close to the mean for 5HT2cR. This screen also
      identifies novel body-fat phenotypes as exemplified by the obese kinase
      suppressor of ras 2 (KSR2) KO mice. These body-fat phenotypes were confirmed upon
      studying additional cohorts of mice for KSR2 and all 13 benchmark KO lines. This
      simple and cost-effective screen appears capable of identifying genes with a role
      in regulating mammalian body fat.

PMID- 18719667
TI  - Influence of age and position on the CT number of adipose tissues in pigs.
AB  - The location of adipose tissue depots is important in determining their
      significance. Research into the physical and chemical differences between these
      depots is therefore of interest. Using image analysis, this paper examines the
      influence of location on the linear attenuation coefficient of adipose tissue for
      X-rays, in computed tomography (as indicated by CT number) at three time points.
      Nine pigs were CT scanned on three separate occasions approximately 1 month
      apart. The mean CT number was -78, -100, and -104 for visceral adipose tissue
      (VAT) from the first to the final scan, respectively. The corresponding CT
      numbers for subcutaneous adipose tissue (SAT) were -80, -101, and -106. There was
      a significant difference between the CT numbers at each location at each scan (P
      values from 0.025 to <0.001) and between the CT numbers for each location at
      different times (P < 0.05). In a separate analysis of the final scan session, the
      mean CT number of adipose tissue at increasing distances from a mathematically
      defined center of the animal was determined. Regression analysis showed that the
      CT number of adipose tissue decreases with increasing distance from the animal's
      center (y = -102.7 - 0.04 x, P < 0.001, where y is the predicted CT number for
      adipose tissue, from the animal center (x = 0) to the skin (x = 100)). It can
      thus be expected that the overall mean CT number for adipose tissue can be used
      as an indicator of the relative quantities of adipose tissue at each location if
      the mean for each is known.

PMID- 18719668
TI  - Overexpression of CART in the PVN increases food intake and weight gain in rats.
AB  - OBJECTIVE: Cocaine- and amphetamine-regulated transcript (CART) codes for a
      hypothalamic neuropeptide, CART (55-102), which inhibits food intake.
      Intracerebroventricular injection of CART (55-102) reduces appetite, but also
      results in motor abnormalities. More recently, studies have demonstrated that
      administration of CART directly into the paraventricular nucleus (PVN) increases
      food intake. To investigate the role of CART in the regulation of energy balance
      in the PVN, we used recombinant adeno-associated virus (rAAV) to overexpress CART
      in the PVN. METHODS AND PROCEDURES: Male Wistar rats were injected with either
      rAAV-encoding CART (rAAV-CART) or rAAV-encoding enhanced green fluorescent
      protein (rAAV-EGFP) as a control. Food intake and body weight were measured
      regularly. Animals were fed on normal-chow diet for the first 93 days of the
      study. After this point, they were fed on high-fat diet. Animals were killed 138
      days postinjection and blood and tissues were collected for analysis. RESULTS:
      Overexpression of CART in the PVN resulted in increased cumulative food intake
      and body weight gain compared with rAAV-EGFP controls when fed normal chow. These
      changes became significant at day 65 and 79, respectively and were accentuated on
      a high-fat diet. A 4% increase in food intake was observed in rAAV-CART animals
      on a normal-chow diet and a 6% increase when fed a high-fat diet. At the end of
      the study, rAAV-CART-treated animals had higher circulating leptin concentrations
      in accord with their higher body weight. DISCUSSION: These data provide further
      evidence that hypothalamic CART plays an orexigenic role.

PMID- 18719669
TI  - Effect of endurance exercise on hepatic lipid content, enzymes, and adiposity in
      men and women.
AB  - Obesity and physical inactivity are independent risk factors for the development
      of nonalcoholic fatty liver disease (NAFLD). We determined the effect of
      endurance exercise training on hepatic lipid content and hepatic enzyme
      concentration in men and women. Waist circumference (WC), percent body fat (BF),
      computed tomography (CT) scans for liver attenuation (inverse relationship with
      hepatic lipid), bilirubin, alanine aminotransferase (ALT), and gamma
      glutamyltransferase (GGT) plasma concentrations were measured before and after 12
      weeks of endurance training in 41 lean and obese men and women. Exercise training
      did not change liver attenuation, body weight, percent BF, bilirubin, or ALT
      concentration, but did lower WC (P < 0.0001), and decreased GGT in men only (P =
      0.01). Obese subjects had a lower liver attenuation than lean subjects (P =
      0.04). Obese women had lower ALT than obese men (P = 0.03). GGT was lower in
      women before and after training. WC was positively correlated with GGT (r = 0.32,
      P = 0.003) and ALT (r = 0.320, P = 0.004) and negatively correlated with liver
      attenuation (r = -0.340, P = 0.03). Percent BF was negatively correlated with
      bilirubin (r = -0.374, P = 0.005). Liver attenuation was negatively correlated
      with ALT (r = -0.405, P = 0.003). Short-term endurance training without weight
      loss does not alter hepatic lipid content. There was a strong relationship
      between GGT/ALT and body composition (percent BF) as well as between ALT and
      hepatic lipid content.

PMID- 18719670
TI  - Retinol-binding protein 4, visceral fat, and the metabolic syndrome: effects of
      weight loss.
AB  - Retinol-binding protein 4 (RBP-4) has been reported to be associated with
      visceral-fat accumulation and parameters of the metabolic syndrome (MetS). In
      this study, we investigated the relationship between RBP-4, visceral fat, and the
      MetS during pronounced weight loss after bariatric surgery. Thirty-six subjects
      were examined before and 2 years after surgery. Abdominal-fat distribution was
      determined by ultrasound, metabolic parameters, and serum RBP-4 levels by
      standard methods. After surgery BMI decreased by 9.07 kg/m(2), visceral-fat
      diameter (VFD) decreased by 60.6%, and RBP-4 serum levels by 16.6%. Change of RBP
      4 levels was associated with reductions of waist (r = 0.364, P = 0.037), waist-to
      hip ratio (WHR) (r = 0.415, P = 0.016), and VFD (r = 0.425, P = 0.010). MetS, as
      defined by International Diabetes Federation (IDF), was present in 19 patients at
      baseline and in nine patients at follow-up. Change in RBP-4 levels was the best
      predictor for the diagnosis of MetS at follow-up. In the subgroup without MetS at
      baseline, the decrease in RBP-4 levels (-28.1% vs. -6.3%, P = 0.020) and
      reduction in VFD (-66.9% vs. -55.0%, P = 0.038) were significantly greater
      compared to the subgroup with MetS. We demonstrate a marked decrease of RBP-4
      levels after bariatric surgery, which correlates with reduction in visceral-fat
      mass. Furthermore, the extent of changes in RBP-4 levels differs according to the
      severity of the MetS.

PMID- 18719671
TI  - Effects on food intake and blood lipids of cannabinoid receptor 1 antagonist
      treatment in lean rats.
AB  - Endocannabinoids act through the cannabinoid receptor 1 (CB1) and has both
      orexigenic and peripheral metabolic effects. It is not yet fully understood
      whether all the beneficial effects on the metabolic profile by CB1 antagonism are
      induced by the weight loss or also by direct peripheral effects. The present
      study was intended to further elucidate this question and to investigate whether
      tolerance development to the hypophagic effect could be attenuated by cyclic
      treatment. We performed an intervention study in 40 lean rats over 4 weeks. The
      rats were divided in four groups: a control group, two groups treated with the
      CB1 antagonist Rimonabant either continuously or cyclically, and one group pair
      fed with the continuous Rimonabant group to obtain the same body weight. During
      the first 6 days, food intake was less in the continuous Rimonabant group
      compared to the control group (P < 0.01). Throughout the study period, the cyclic
      Rimonabant group had a smaller food intake than the continuous Rimonabant group
      (P < 0.05). After 4 weeks, the cyclic Rimonabant group had a reduced weight gain
      compared to the control group (P < 0.05). Serum levels of glycerol and free fatty
      acids (nonesterified fatty acid, NEFA) were significantly reduced in both treated
      groups compared to the untreated groups, and levels of triglycerides showed the
      same tendency. Cyclic treatment with Rimonabant is able to inhibit tolerance
      development on food intake, which resulted in reduction in body weight.
      Rimonabant treatment is associated with reduced serum levels of glycerol, NEFA,
      and triglyceride which seem independent of body weight changes.

PMID- 18719672
TI  - Calcium supplementation does not alter lipid oxidation or lipolysis in
      overweight/obese women.
AB  - Based on cell culture and studies in mice, increased dietary calcium appears to
      stimulate lipolysis and could possibly reduce body adiposity through hormonal
      influences on adipocyte calcium uptake. In this study, we investigated the
      effects of 1,500 mg supplemental calcium daily for 3 months on hormones
      regulating calcium and energy metabolism and rates of lipid oxidation and
      lipolysis in overweight women. Fifteen overweight (BMI > 25 kg/m(2))
      premenopausal women were supplemented with 1,500 mg of calcium, as CaCO(3), per
      day for 3 months while maintaining their usual diets and activity levels.
      Baseline and endpoint measurements were obtained after the subjects consumed a
      standardized 25% fat diet for 4 days. Lipid oxidation was measured by indirect
      calorimetry, lipolysis by infusion of deuterated glycerol, and body fat by dual
      energy X-ray absorptiometry. Urinary calcium, circulating levels of hormones
      involved in energy and lipid metabolism (insulin, leptin, and adiponectin) or
      calcium metabolism (25(OH)D, 1,25(OH)(2)D), and parathyroid hormone (PTH)) were
      also measured. Urinary levels of calcium (P = 0.005) increased and 1,25(OH)(2)D
      declined (P = 0.03). However other parameters, including body weight, body fat,
      PTH, insulin, leptin, adiponectin, 25(OH)D, as well as rates of lipid oxidation
      and lipolysis were not altered by calcium supplementation. Calcium
      supplementation for 3 months increased urinary calcium excretion, decreased
      circulating levels of 1,25(OH)(2)-D, but had no effect on rates of lipid
      oxidation or lipolysis, in these overweight women.

PMID- 18719673
TI  - Independent influence of insulin, catecholamines, and thyroid hormones on
      metabolic syndrome.
AB  - The objective of this study was to examine whether metabolic syndrome, defined
      according to adult treatment panel III criteria, is associated with insulin,
      catecholamines, and thyroid hormones, independently of age and gender. A cohort
      of 651 euthyroid overweight and obese patients, 440 women and 211 men, aged 18-68
      years, were examined. Central fat accumulation (indirectly measured by waist
      circumference), fasting thyroid-stimulating hormone (TSH), FT(3), FT(4), insulin,
      glucose, and lipid (cholesterol, HDL-cholesterol, and triglyceride) serum
      concentrations, 24-h urinary catecholamines, and the level of insulin resistance
      (estimated by homeostasis model assessment for insulin resistance (HOMA(IR)))
      were measured. Patients with metabolic syndrome showed higher insulin (P < 0.001)
      and FT(3) (P < 0.001) serum levels and higher 24-h urinary noradrenaline (P <
      0.001) than subjects without this syndrome. The number of metabolic syndrome
      parameters was directly associated with insulin (P < 0.001) and FT(3) (P < 0.05)
      serum levels, and with 24-h urinary noradrenaline (P < 0.001) in the whole
      population. When a multiple regression analysis was performed with the metabolic
      syndrome as the dependent variable, and age, gender, and insulin, and TSH, FT(3),
      FT(4) serum levels, and 24-h urinary noradrenaline and adrenaline as independent
      variables, the metabolic syndrome maintained an independent positive association
      with age (P < 0.001), male sex (P < 0.001), insulin (P < 0.001), and 24-h urinary
      noradrenaline (P < 0.001). In conclusion, this study suggests that insulin and
      noradrenaline cooperate independently to the development of the metabolic
      syndrome.

PMID- 18719674
TI  - Family meal frequency and weight status among adolescents: cross-sectional and 5
      year longitudinal associations.
AB  - This study examined cross-sectional and 5-year longitudinal associations between
      the frequency of family meals and overweight status (>85th percentile for age and
      gender) in a large, diverse population of adolescents (n = 2,516). The population
      included two cohorts (midadolescence to young adulthood, n = 1,710, and early
      adolescence to midadolescence, n = 806). Logistic regression models tested cross
      sectional and longitudinal (1999-2004) associations between family meal frequency
      and overweight status. Two sets of models are presented: (i) models adjusted only
      for baseline demographic characteristics and (ii) models also adjusted for
      physical activity, sedentary behaviors, and energy intake. Longitudinal models
      adjusted for baseline overweight status. Although significant inverse
      associations between family meal frequency and overweight status were observed
      for early adolescent females in all cross-sectional models (P < 0.001),
      longitudinal associations were not significant. Neither cross-sectional nor
      longitudinal associations were significant for males of either cohort and older
      females in any models. Young adolescent females who do not eat meals with their
      families may be at risk for overweight; however, the increased risk may not
      persist over a 5-year period. Eating family meals during high school may not
      protect against overweight during young adulthood. Although previous longitudinal
      research has suggested significant dietary and psychosocial benefits related to
      family meal frequency, the weight-related benefits of family meals may be more
      complex and deserving of further study, including an examination of the quality
      and quantity of food consumed at family meals.

PMID- 18719675
TI  - Epicardial adipose tissue extent: relationship with age, body fat distribution,
      and coronaropathy.
AB  - Epicardial fat is a relatively neglected component of the heart and could be an
      important risk factor of cardiac disease. The objective of our study was to
      assess the relationship between epicardial adipose tissue (EAT) extent, fat
      distribution, and coronaropathy in a group of adult victims of accidental or
      suspicious sudden death. In 56 cadavers, we performed 34 measurements of EAT from
      five computerized photographs of the heart (anterior and posterior faces, and
      three ventricle transversal slices) and analyzed their relationship with
      anthropometric markers of adiposity (BMI, waist and leg circumference, thickness
      of abdominal and thigh subcutaneous adipose tissue (SAT)), with the presence and
      staging of coronary artery disease (CAD), and with markers of myocardial
      hypertrophy. Simple linear regressions showed that EAT measurements are highly
      intercorrelated (r from 0.4 to 0.6, P < 0.001), and correlate with age, waist
      circumference, and heart weight, and to a lesser extent, with BMI, abdominal SAT
      thickness, and leg SAT thickness. Multiple regression showed that age, waist
      circumference, and heart weight significantly and independently correlate with
      EAT (P < 0.0001). No other anthropometric measurement was found independently
      correlated with EAT. The EAT/myocardium ratios correlated positively with age and
      waist circumference. Anterior and posterior areas of EAT were found significantly
      increased in patients with CAD and correlated positively with CAD staging (P =
      0.0034, r = 0.38). Anterior EAT surface was found positively associated with CAD
      (P = 0.01), independently of age and other adiposity measurements. Prospective
      studies are needed to assess the risk of occurrence/progression of CAD that
      relate to EAT excess.

PMID- 18719676
TI  - Weight loss expectations and goals in a population sample of overweight and obese
      US adults.
AB  - The purpose of this study was to investigate weight loss expectations and goals
      in a population sample of US adults who planned to make a weight loss attempt,
      and to examine predictors of those expectations and goals. Participants were 658
      overweight and obese adults (55% women, mean age = 47.9 years, BMI = 31.8
      kg/m(2)) who responded to a telephone survey about weight loss. Respondents
      reported weight loss expectations (i.e., reductions they realistically expected)
      and goals (i.e., reductions they ideally desired) for an upcoming "serious and
      deliberate" weight loss attempt. They also reported the expectations they had,
      and the reductions they actually achieved, in a previous attempt. Respondents'
      weight loss expectations for their upcoming attempt (8.0% reduction in initial
      weight) were significantly more modest than their goals for that attempt (16.8%),
      and smaller than the losses that they expected (12.0%), and achieved (8.9%) in
      their most recent past attempt (Ps <or= 0.003). Women and participants with
      higher BMIs had greater weight loss expectations and goals. After controlling for
      BMI, age, and gender, previous weight loss was unrelated to expectations (but was
      inversely related to goals) for the upcoming weight loss attempt. Results suggest
      that overweight and obese individuals can select realistic weight loss
      expectations that are more modest than their ideal goals. BMI and gender appear
      to be more important than previous weight loss experiences in determining
      expectations among persons planning a weight loss attempt.

PMID- 18719677
TI  - Obesity and the likelihood of sexual behavioral risk factors for HPV and cervical
      cancer.
AB  - Obesity is associated with higher cervical cancer mortality, but its relationship
      with sexual behavioral risk factors that predispose women to human papilloma
      virus (HPV) and cervical cancer is unclear. We used data from 3,329 women
      participants, aged 20-59 years, of the 1999-2004 National Health and Nutrition
      Examination Survey, to analyze the relationship between BMI and age at first
      intercourse, number of sexual partners, condom use during sexual activity,
      history of sexually transmitted disease (STD), herpes simplex virus 2 (HSV-2)
      seropositivity, and HPV prevalence. BMI was not associated with the prevalence of
      HPV. Mildly obese women (BMI 30.0-34.9 kg/m(2)) were least likely to report a STD
      history (9% vs. 13% in normal weight) and >or=2 sexual partners in the previous
      year (8% vs. 13%) while overweight women (BMI 25.0-29.9 kg/m(2)) were least
      likely to report >or=10 lifetime partners; among those with multiple partners,
      BMI was not associated with sexual activity without condoms in the past month.
      After adjustment for age, race/ethnicity, and education, women with higher BMI
      were less likely to report sexual behavioral risk factors than normal-weight
      women; however, odds ratios were only significant for mildly obese women for
      reporting a STD history (0.74, 95% confidence interval 0.55-0.99) and having
      >or=2 sexual partners in the last year (0.57, 0.39-0.85). Higher BMI was not
      associated with HSV-2 seropositivity after adjustment. HPV and sexual behavioral
      risk factors for HPV and cervical cancer are not more prevalent in obese than
      normal-weight women and unlikely to account for higher-observed cervical cancer
      mortality in obese women.

PMID- 18719678
TI  - High-fat diet-induced obesity leads to resistance to leptin-induced cardiomyocyte
      contractile response.
AB  - Levels of the obese gene product leptin are often elevated in obesity and may
      contribute to obesity-induced cardiovascular complications. However, the role of
      leptin in obesity-associated cardiac abnormalities has not been clearly defined.
      This study was designed to determine the influence of high-fat diet-induced
      obesity on cardiac contractile response of leptin. Mechanical and intracellular
      Ca(2+) properties were evaluated using an IonOptix system in cardiomyocytes from
      adult rats fed low- and high-fat diets for 12 weeks. Cardiomyocyte contractile
      and intracellular Ca(2+) properties were examined including peak shortening,
      duration and maximal velocity of shortening/relengthening (TPS/TR(90), +/-dl/dt),
      Fura-2-fluorescence intensity change (DeltaFFI), and intracellular Ca(2+) decay
      rate (tau). Expression of the leptin receptor (Ob-R) was evaluated by western
      blot analysis. High-fat diet increased systolic blood pressure and plasma leptin
      levels. PS and +/-dl/dt were depressed whereas TPS and TR(90) were prolonged
      after high-fat diet feeding. Leptin elicited a concentration-dependent (0-1,000
      nmol/l) inhibition of PS, +/-dl/dt, and DeltaFFI in low-fat but not high-fat diet
      fed rat cardiomyocytes without affecting TPS and TR(90). The Janus kinase 2
      (JAK2) inhibitor AG490, the mitogen-activated protein kinase (MAPK) inhibitor
      SB203580, and the nitric oxide synthase (NOS) inhibitor L-NAME abrogated leptin
      induced cardiomyocyte contractile response in low-fat diet group without
      affecting the high-fat diet group. High-fat diet significantly downregulated
      cardiac expression of Ob-R. Elevation of extracellular Ca(2+) concentration
      nullified obesity-induced cardiomyocyte mechanical dysfunction and leptin-induced
      depression in PS. These data indicate presence of cardiac leptin resistance in
      diet-induced obesity possibly associated with impaired leptin receptor signaling.

PMID- 18719682
TI  - New UV switch makes worms move.

PMID- 18719679
TI  - Gender related differences in paraoxonase 1 response to high-fat diet-induced
      oxidative stress.
AB  - OBJECTIVE: To evaluate the influence of the pro-oxidant and proinflammatory state
      related to dietary obesity on serum paraoxonase 1 (PON1) activity in male and
      female rats. METHODS AND PROCEDURES: Adult Wistar rats of both genders were fed
      on a high-fat diet to induce weight gain or standard diet for 14 weeks. Body
      weight was assessed weekly and food intake fortnightly throughout the dietary
      treatment. Biometrical parameters and serum lipid profile, glucose, insulin, and
      adipokine levels were measured. To assess the effect of dietary obesity on
      oxidative stress, levels of liver and serum thiobarbituric acid reactive
      substances, liver protein carbonyl groups, liver antioxidant enzymes activities,
      and serum PON1 activities were measured. RESULTS: High-fat diet feeding induced a
      significant body weight gain in both male and female rats, as well as a reduction
      of liver antioxidant protection. High-fat diet increased serum lipid peroxides in
      male rats and reduced serum PON1 activities and serum apolipoprotein A-I (apoA-I)
      levels in females, although did not alter serum PON1 or apolipoprotein J (apoJ)
      levels. DISCUSSION: Our results reveal a gender dimorphism in the high-fat diet
      induced reduction of serum PON1 activity, which is likely to be related to the
      greater obese and proinflammatory state achieved in female rats. We suggest that
      the enhanced oxidative stress caused by dietary increased body weight, on leading
      to high-density lipoprotein (HDL), apoA-I or PON1 oxidation could entail the
      destabilization of the PON1 association to HDL or a direct inactivation of PON1
      enzymatic activity, thus accounting for the decreased serum PON1 activities
      observed in female rats.

PMID- 18719680
TI  - Successful weight-loss maintenance in relation to method of weight loss.
AB  - This study examined the relation between method of weight loss and long-term
      maintenance among successful weight losers enrolled in a weight-loss maintenance
      trial. Participants were 186 adults (mean age = 51.6 +/- 10.7 years, mean BMI =
      28.6 +/- 4.7 kg/m(2)) enrolled in the STOP Regain trial who had lost at least 10%
      of their body weight in the past 2 years using a very low-calorie diet (VLCD; n =
      24), commercial program (n = 95), or self-guided approach (n = 67). Participants
      were randomized to a weight-maintenance intervention delivered face to face or
      over the internet or to a newsletter control condition, and followed for 18
      months. At study entry, individuals who had used a VLCD had achieved a weight
      loss of 24% of their maximum weight within the past 2 years compared to 17%
      achieved by those who had used a commercial program or self-guided approach (P <
      0.001). However, individuals who had used a VLCD regained significantly more
      weight than the other two groups and by 6 months, there were no significant
      differences in overall percent weight loss (i.e., initial weight loss and
      maintenance) between VLCD, commercial, and self-guided methods. In contrast,
      individuals who had used a self-guided approach maintained their weight losses
      from baseline through 18 months. The large initial weight losses achieved by
      individuals who had used a VLCD were not maintained over time, whereas
      individuals who had used a self-guided approach maintained their initial weight
      losses with the greatest success. The generalizability of these findings is
      limited by the sizeable weight losses achieved by study participants.

PMID- 18719683
TI  - Making songs stick in sparrows' heads.

PMID- 18719686
TI  - Drug menus in protocol applications. Allow flexibility, with limits.

PMID- 18719687
TI  - Drug menus in protocol applications.

PMID- 18719688
TI  - Drug menus in protocol applications. A la carte is OK.

PMID- 18719689
TI  - Drug menus in protocol applications. Formalize SOPs.

PMID- 18719690
TI  - Brain lesion in a Wistar rat. Encephalitozoonosis.

PMID- 18719692
TI  - Intraoral examination in rabbits.
AB  - Dental examination should be included in all physical examinations of rabbits
      because they have continuously growing teeth and are predisposed to dental
      disease. This column describes the procedure and equipment used for oral
      examination in rabbits.

PMID- 18719693
TI  - The foraging ball as a quick and easy enrichment device for pigs (Sus scrofa).
AB  - Providing research pigs with enrichment objects can encourage species-typical
      behavior such as rooting and foraging. The authors gave pigs hard plastic
      'foraging balls' that resembled enrichment devices commonly used for nonhuman
      primates. Holes were custom-drilled into the balls, and animal caretakers filled
      them with palatable food items such as jellybeans, unsalted peanuts, cereal,
      Beggin' Strips, primate biscuits and dog biscuits. Staff members suspended the
      balls from chains in pigs' enclosures, ensuring that toys did not touch the
      floor. All pigs manipulated the balls and were able to obtain treats that were
      supplemental to their standard diet. The simple and effective enrichment device
      was easily incorporated into the daily routines of research facilities, with
      little disruption to schedules.

PMID- 18719694
TI  - Disposable plastic rodent feeders for use in an automated filling system.
AB  - Rodent feeder devices are often made of reusable, sanitizable materials such as
      glass and stainless steel. As part of an initiative at the authors' facility to
      automate the feeder filling process, disposable plastic feeding cups were
      proposed as a preferable alternative to standard feeders for use in a filling
      machine. The authors tested and validated designs for rodent meal-type feeder
      assemblies that incorporated plastic cups. Assemblies included stainless steel
      shields that prevented rats and mice from chewing on the plastic cups while
      allowing them full access to food. The use of disposable feeder cups that are
      filled and sealed automatically reduces labor associated with sanitation, enables
      staff to prepare feeders for several weeks in advance and limits personnel
      contact with feed that may contain harmful chemicals.

PMID- 18719695
TI  - Effects of housing density on Long Evans and Fischer 344 rats.
AB  - At many breeding facilities, rats are housed at relatively high densities until
      they are 5 weeks old, at which point they are either shipped for research or
      rehoused at standard cage densities according to weight. The authors carried out
      a pilot study in Long Evans and in Fischer 344 rats to investigate whether
      continuing to house rats at high densities (24 in(2) floor space per rat) past
      the age of 5 weeks, through puberty and into adulthood would alter behavioral or
      physiological parameters compared with raising rats at standard densities (about
      72 in(2) floor space per rat). After rats reached puberty, the authors rehoused
      them with unfamiliar cagemates. The researchers evaluated clinical and behavioral
      signs of stress, weight, blood glucose concentration, white blood cell count and
      serum corticosterone concentration. Overall, cage density had little effect on
      the parameters measured, though gender seemed to affect stress in Long Evans
      rats. The results suggest that rats of these strains can be raised at the higher
      densities tested until any age and regrouped with unfamiliar cagemates without
      compromising rats' welfare or subsequent experimental data.

PMID- 18719696
TI  - 'Nuclear' is not the question.

PMID- 18719697
TI  - Nuclear energy for the future.

PMID- 18719698
TI  - Greater tolerance for nuclear materials.

PMID- 18719699
TI  - Nuclear energy--safe and secure? Interview by Joerg Heber.

PMID- 18719701
TI  - Magnetic molecules: Chirality and magnetism shake hands.

PMID- 18719702
TI  - Biological materials: Fishing for compliance.

PMID- 18719704
TI  - Material witness: Old gold.

PMID- 18719703
TI  - Condensed-matter physics: Complex oxides on fire.

PMID- 18719705
TI  - Classical and quantum routes to linear magnetoresistance.
AB  - The hallmark of materials science is the ability to tailor the microstructure of
      a given material to provide a desired response. Carbon mixed with iron provides
      the steel of buildings and bridges; impurities sprinkled in silicon single
      crystals form the raw materials of the electronics revolution; pinning centres in
      superconductors let them become powerful magnets. Here, we show that either
      adding a few parts per million of the proper chemical impurities to indium
      antimonide, a well-known semiconductor, or redesigning the material's structure
      on the micrometre scale, can transform its response to an applied magnetic field.
      The former approach is purely quantum mechanical; the latter a classical
      outgrowth of disorder, turned to advantage. In both cases, the magnetoresistive
      response--at the heart of magnetic sensor technology--can be converted to a
      simple, large and linear function of field that does not saturate. Harnessing the
      effects of disorder has the further advantage of extending the useful
      applications range of such a magnetic sensor to very high temperatures by
      circumventing the usual limitations imposed by phonon scattering.

PMID- 18719706
TI  - Vertically oriented hexagonal mesoporous films formed through nanometre-scale
      epitaxy.
AB  - Polymer- and surfactant-templated mesoporous inorganic materials offer a unique
      combination of controllable nanoscale architecture, materials variation and low
      cost solution processing. Inorganic materials can be produced with a range of
      periodic pore structures, with feature size ranging from 2 to 30 nm, and from a
      diverse set of materials. Unfortunately in thin-film form, the pores of the
      ubiquitous hexagonal honeycomb phase tend to lie in the plane of the substrate
      making these materials unsuitable for applications where diffusion into the pores
      is required. Here, we show that nanometre-scale epitaxy on a patterned substrate
      can be used to form vertically oriented pores in honeycomb-structured films. We
      use the surface of cubic mesoporous films to form the pattern; as such, our
      method does not sacrifice the simple processing advantages of a self-assembled
      system. A precise lattice match between the hexagonal and cubic films is needed
      for vertical orientation, a condition that can be achieved using mixed templates
      or selective pore swelling. Pore orientation is characterized by a combination of
      microscopy and diffraction. Here, we present alignment data on oriented nanopores
      in the 10-15 nm range, but the method should be applicable across the 2-30 nm
      pore size range of these self-organized materials.

PMID- 18719707
TI  - Endogenous small interfering RNAs in animals.
AB  - Until recently, only nematodes among animals had a well-defined endogenous small
      interfering RNA (endo-siRNA) pathway. This has changed dramatically with the
      recent discovery of diverse intramolecular and intermolecular substrates that
      generate endo-siRNAs in Drosophila melanogaster and mice. These findings suggest
      broad and possibly conserved roles for endogenous RNA interference in regulating
      host-gene expression and transposable element transcripts. They also raise many
      questions regarding the biogenesis and function of small regulatory RNAs in
      animals.

PMID- 18719708
TI  - Mammalian Rho GTPases: new insights into their functions from in vivo studies.
AB  - Rho GTPases are key regulators of cytoskeletal dynamics and affect many cellular
      processes, including cell polarity, migration, vesicle trafficking and
      cytokinesis. These proteins are conserved from plants and yeast to mammals, and
      function by interacting with and stimulating various downstream targets,
      including actin nucleators, protein kinases and phospholipases. The roles of Rho
      GTPases have been extensively studied in different mammalian cell types using
      mainly dominant negative and constitutively active mutants. The recent
      availability of knockout mice for several members of the Rho family reveals new
      information about their roles in signalling to the cytoskeleton and in
      development.

PMID- 18719709
TI  - A complex barcode underlies the heterogeneous response of p53 to stress.
AB  - The tumour suppressor p53 is activated following stress and initiates a
      heterogeneous response in a cell-, tissue- and stress-dependent manner. This
      heterogeneity is reflected in the different physiological outcomes that follow
      p53 activation. One mechanism that may contribute to this variability is the
      promoter selectivity of p53 target genes. p53 is at the hub of numerous
      signalling pathways that are triggered in response to particular stresses, all of
      which can leave their mark on p53 by way of post-translational modifications and
      interactions with cofactors. The precise combination of these marks, much like
      the bars in a barcode, dictates the behaviour of p53 in any given situation.

PMID- 18719710
TI  - Conserved functions of the pRB and E2F families.
AB  - Proteins that are related to the retinoblastoma tumour suppressor pRB and the E2F
      transcription factor are conserved in many species of plants and animals. The
      mammalian orthologues of pRB and E2F are best known for their roles in cell
      proliferation, but it has become clear that they affect many biological
      processes. Here we describe the functions of pRB-related proteins and E2F
      proteins that have emerged from genetic and biochemical experiments in
      Caenorhabditis elegans and Drosophila melanogaster. The similarities that have
      been observed between worms, flies and mammals provide insight into the core
      activities of pRB and E2F proteins and show how a common regulatory module can
      control various biological functions in different organisms.

PMID- 18719711
TI  - Cardiologists and the management of blood sugar: a Chinese perspective.

PMID- 18719712
TI  - Chronic pain assessment: a seven-factor model.
AB  - BACKGROUND: There are many measures assessing related dimensions of the chronic
      pain experience (eg, pain severity, pain coping, depression, activity level), but
      the relationships among them have not been systematically established. OBJECTIVE:
      The present study set out to determine the core dimensions requiring assessment
      in individuals with chronic pain. METHODS: Individuals with chronic pain (n=126)
      completed the Beck Anxiety Inventory, Beck Depression Inventory, Beck
      Hopelessness Scale, Chronic Pain Coping Index, Multidimensional Pain Inventory,
      Pain Catastrophizing Scale, McGill Pain Questionnaire--Short Form, Pain
      Disability Index and the Tampa Scale of Kinesiophobia. RESULTS: Before an
      exploratory factor analysis (EFA) of the nine chronic pain measures, EFAs were
      conducted on each of the individual measures, and the derived factors (subscales)
      from each measure were submitted together for a single EFA. A seven-factor model
      best fit the data, representing the core factors of pain and disability, pain
      description, affective distress, support, positive coping strategies, negative
      coping strategies and activity. CONCLUSIONS: Seven meaningful dimensions of the
      pain experience were reliably and systematically extracted. Implications and
      future directions for this work are discussed.

PMID- 18719713
TI  - Use of pain threshold reports to satisfy social needs.
AB  - OBJECTIVE: To examine the hypothesis that experimental threats to social
      belongingness, interacting with individual differences in attachment security,
      cause modification of pain threshold reports by individuals who report high pain
      thresholds at baseline. METHODS: In each of three studies, baseline pain
      threshold and tolerance were assessed in response to a pain task (cold pressor
      pain in Studies 1 and 2, finger pressure pain in Study 3). Participants then
      completed a measure of attachment security and were randomly assigned to a social
      exclusion or control condition (exclusion from a computer game in Study 1,
      recalling past rejection experiences in Studies 2 and 3). The pain task was
      administered again to examine the effects on pain threshold and tolerance.
      RESULTS: Those with high anxious attachment and high baseline pain thresholds
      reported higher postmanipulation pain thresholds in the exclusion conditions than
      in the control conditions. Those with low anxious attachment and high baseline
      pain thresholds reported lower postmanipulation pain thresholds in the exclusion
      conditions than in the control conditions. No differences were found for pain
      tolerance. CONCLUSIONS: Across studies, results suggested that postmanipulation
      pain threshold reports of individuals with high baseline pain thresholds were
      particularly responsive to social exclusion. The form of the response was
      dependent on the level of anxious attachment. The present studies provide
      evidence that variance in pain threshold reports not accounted for by pain
      intensity may reflect the use of pain reports to satisfy social needs. This work
      also suggests that baseline measures of pain thresholds may, in interaction with
      psychological variables, have predictive power beyond serving as a control
      variable.

PMID- 18719714
TI  - Achieving organizational change in pediatric pain management.
AB  - BACKGROUND: Pain in hospitalized children is often undertreated. Little
      information exists to guide the process of organizational change with a view to
      improving pain management practices. OBJECTIVES: To describe the process and
      results of a hospital-wide review of pain management practices designed to
      identify deficiencies in service provision and recommend directions for change in
      a pediatric hospital. DESIGN: Prospective consultation of the clinical staff of a
      specialist pediatric hospital, using qualitative research methodology involving
      semistructured individual and group interviews. Recommendations based on the
      interview findings were made by a hospital-appointed working party. RESULTS: A
      total of 454 staff (27% of all clinical staff) from a variety of professional
      backgrounds, representing almost every hospital unit or department, were
      interviewed. Procedural and persistent (chronic) pain was identified as the area
      needing the most improvement. Barriers to improving pain management included
      variability in practice, outmoded beliefs and inadequate knowledge, factors which
      were seen to contribute to a culture of slow or no change. Recommendations of the
      working party and changes achieved after the review are described. CONCLUSION:
      The review process identified deficiencies in the management of pain in children,
      and barriers to its effective management. With institutional support, the present
      review has guided improvement.

PMID- 18719715
TI  - Validation of a French-Canadian version of the Pain Disability Index.
AB  - OBJECTIVE: To examine the psychometric properties of the Index de l'incapacite
      reliee a la douleur, a French-Canadian version of the Pain Disability Index
      (PDI). METHODS: A total of 176 chronic pain patients (94 women, 82 men) completed
      the French-Canadian version of the PDI (PDI-CF), as well as other pain-related
      measures. A subset of 52 patients (27 women, 25 men) also completed a lifting
      task designed to assess physical tolerance and pain behaviour. RESULTS:
      Confirmatory factor analysis of the PDI-CF supported the two-factor structure of
      the original PDI. Reliability analyses revealed that the PDI-CF total score had a
      high degree of internal consistency, comparable with the original PDI. The PDI-CF
      total score was significantly correlated with self-reported pain, pain
      catastrophizing, depressive symptoms, fear of movement or (re)injury, lift
      duration and pain behaviours. CONCLUSIONS: The results suggest that the PDI-CF is
      a reliable and valid measure of self-reported disability that is psychometrically
      similar to the original scale.

PMID- 18719716
TI  - Prospective relation between catastrophizing and residual pain following knee
      arthroplasty: two-year follow-up.
AB  - BACKGROUND: Pain is the primary indication for both primary and revision total
      knee arthroplasty (TKA); however, most arthroplasty outcome measures do not take
      pain into account. OBJECTIVE: To document the prospective pain experience
      following TKA, with subjective pain-specific questionnaires to determine if
      comorbidities, preoperative pain or preoperative pain catastrophizing scores are
      predictive of long-term pain outcomes. METHODS: Fifty-five patients with a
      primary diagnosis of osteoarthritis of the knee, who were scheduled to undergo
      TKA, were asked to fill out the McGill Pain Questionnaire (MPQ) and the Pain
      Catastrophizing Scale (PCS) preoperatively and at three, 12 and 24 months follow
      up. Comorbidities were extracted from the Queen Elizabeth II Health Sciences
      Centre health information system. RESULTS: The overall response rate (return of
      completed questionnaires) was 84%. There was a significant decrease in the MPQ
      scores (P<0.05) postoperatively. PCS scores did not change over time. Receiver
      operating characteristic curves revealed the number of comorbidities per patient
      predicted the presence of pain postoperatively, as documented by the numerical
      rating subscale of the MPQ at 24 months (P<0.05). Receiver operating
      characteristic curves for preoperative PCS and rumination subscale scores
      predicted the presence of pain, as measured by the Pain Rating Index subscale of
      the MPQ at 24 months (P<0.05). Preoperative PCS scores and comorbidities were
      significantly higher in the persistent pain group (P<0.05). CONCLUSIONS: The
      number of comorbidities predicted the presence of pain at 24 months follow-up
      and, for the first time, preoperative PCS scores were shown to predict chronic
      postoperative pain. This may enable the identification of knee arthroplasty
      patients at risk for persistent postoperative pain, thus allowing for efficient
      administration of preoperative interventions to improve arthroplasty outcomes.

PMID- 18719717
TI  - [The Public Health National plan: thesis, antithesis, synthesis].

PMID- 18719718
TI  - [Prevalence of epithelial squamous cell abnormalities and associated factors in
      women of a rural town of Colombia].
AB  - INTRODUCTION: In spite of implementation of cytology-based cervical cancer
      screening in Colombia, mortality rates remain stable. The description of factors
      associated to cervical pre-neoplasic lesions is needed to establish strategies
      for mortality prevention. OBJECTIVE: The prevalence of epithelial squamous cell
      abnormalities was determined to explore the association of cytology abnormalities
      with described risk factors. MATERIALS AND METHODS: This population-based, cross
      sectional study included 739 women randomly selected by age. A validated face-to
      face questionnaire and conventional cervical cytology were used to collect the
      information. To establish the association between cervical abnormalities and some
      qualitative variables, the independent chi squared test was used. We also
      calculated prevalence ratio with their 95% confidence intervals. A logistic
      regression model was used to explore variables that potentially explain cytology
      abnormalities. RESULTS: The prevalence of squamous cell abnormality was 15.8%.
      Among women with abnormal cytology, 10% presented atypical squamous cells of
      undetermined significance, 3.9% low grade squamous intra-epithelial lesion and
      1.9% high grade squamous intra-epithelial lesion. The adjusted logistical
      regression analysis showed that history of sexual transmitted disease, two or
      more sexual partners during entire life and previous abnormal cytology were
      associated with cytology abnormalities. CONCLUSION: The relation of epithelial
      squamous cell abnormalities with sexual behavior history reflexes the link
      between human papiloma virus infection and cervical cancer pre-neoplasic lesions.
      The frequency of use and knowledge about the purpose of cytology were factors
      that suggested other diagnostic limitations such as quality of cervical cytology
      or barriers to access health care. These latter factors may be the underlying
      basis for the high cervical cancer mortality rates.

PMID- 18719719
TI  - [Make your own diagnosis: first part].

PMID- 18719720
TI  - [Biopercular syndrome: report of two cases and literature review].
AB  - The anterior opercular or biopercular syndrome is a cortical pseudobulbar palsy
      due to bilateral lesions of the anterior brain operculum. It is characterized by
      preservation of reflex function and automatic activity, without mental
      impairment. Two cases are reported herein and the relevant literature reviewed.
      The first case was a 73-year-old female with a history of a stroke occurring
      seven years previously, without sequelae in the interim. She presented with
      sudden loss of consciousness. The neurological examination showed a right facial
      central palsy and anarthria, with reflex acts such as smiling, blinking and
      yawning, not elicited by commands; she also had a right hemiparesis and walking
      impairment. A brain CT scan showed an old ischemic infarction in the region of
      the right medial cerebral artery. Because the right motor involvement did not
      correlate with the findings of the initial CT scan, another CT scan two days
      later showed an acute brain infarction in the vicinity of the left medial
      cerebral artery. The second case was an 8-year-old girl with mental retardation
      and impairment of verbal development, caused by of biopercular pachygyria. Facio
      pharyngo-glosso-masticatory diplegia and volitional selective palsy of the oro
      facial muscles was seen in both patients. The neuropsychological assessment
      showed cognitive, emotional and social interaction impairment in both cases -as
      part of the frontal convexity syndrome in the first case and of mental
      retardation in the second. The two patients had difficulty in mastication and
      swallowing. The prognosis for recovery of verbal capacity is poor, although
      generally most patients recover the ability to swallow.

PMID- 18719721
TI  - [Right to die with dignity?].
AB  - The right to die with dignity is an ill-defined concept, with multiple, often
      inappropriate, interpretations. The current proposition is that the physician
      take full responsibility for protecting the patients rights, for ensuring a
      rational use of resources and for overseeing the decision-making process such
      that the information is adequate and the steps proportioned. This responsibility
      extends not only to the health status of the patient situation, to the patients
      prognosis, and to his/her expectations and wishes, but also to the benefits
      foreseen and to the cost-benefit ratio. Emphasis is placed on two aspects of this
      relationship. First, dignity can be interpreted in many ways and sometimes, in
      the name of dignity, the patient is exposed (or exposes him/herself) to
      suffering, pain and complications that can be avoided. Second, when no reasonable
      probability of survival is present and a better quality of life is impossible,
      efforts are better redirected to offering a better quality of death.

PMID- 18719722
TI  - [Gametocytemia in falciparum malaria treated with amodiaquine or artesunate].
AB  - INTRODUCTION: Antimalarial treatment effects on Plasmodium falciparum
      gametocytemia has been the focus of few studies in the Americas. OBJECTIVE:
      Relationships are described that occur between falciparum gametocytemia and the
      treatment with amodiaquine-sulfadoxine-pyrimethamine, artesunate-sulfadoxine
      pyrimethamine or amodiaquine-artesunate. MATERIALS AND METHODS: The experimental
      design consisted of a randomized selection of patients not balanced or blinded. A
      total of 241 patients were evaluated, residents of Turbo, El Bagre and Zaragoza
      (Antioquia, Colombia). The follow up occurred 21-28 days after antimalarial
      treatment. The World Health Organization (1998) protocol was used. RESULTS: The
      therapeutic efficacy of amodiaquine-sulfadoxine-pyrimethamine, artesunate
      sulfadoxine-pyrimethamine and amodiaquine-artesunate were equal at day 21 of the
      follow up. Four cases (1.7%) were therapeutic failures. Amodiaquine-sulfadoxine
      pyrimethamine was less effective than the artesunate treatments in reducing the
      gametocyte load. On day 7, none of the three treatments had eliminated completely
      the gametocytes. Most patients (56.0%) were observed not to have circulating
      gametocytes pre-treatment and did not develop them later. CONCLUSION: The three
      treatment schemes were similar in their therapeutic efficacy and in their
      incapacity to eliminate gametocytes at day seven.

PMID- 18719723
TI  - [In vitro susceptibility of Colombian Plasmodium falciparum isolates to different
      antimalarial drugs].
AB  - INTRODUCTION: The in vitro assays for susceptibility of Plasmodium falciparum to
      antimalarial drugs are important tools for monitoring drug resistance, however
      few such studies have been undertaken in Colombia. OBJECTIVE: P. falciparum
      isolates were obtained from several municipalities in western Colombia (Uraba,
      Bajo Cauca, Pacific Coast) and characterized for their in vivo susceptibility to
      chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), quinine (QN) and artesunate
      (AS). MATERIAL AND METHODS: Patients with only P. falciparum infection
      (parasitemia=1,000 rings/microl) were included. Each antimalaria drug was tested
      with 7 dilutions, two-fold doses, with 2 replications and its effect evaluated
      using the histidine-rich protein (HRP-2) antigen detection method. Controls
      included FCB2 (chloroquine-resistant) and NF54 (chloroquine-sensitive) strains.
      IC50>100, 80, 64, 500 and 10.5 nM were used as the threshold criteria of
      resistance to CQ, AQ, MQ, QN and AS, respectively. Results. Twenty-five isolates
      were evaluated from Uraba (18), Bajo Cauca (2) and the Pacific Coast (5). The
      mean IC50 obtained with CQ, AQ, MQ, QN and AS were 422.9; 131.4; 56.3; 269.7 and
      1.9 nM, respectively, and the number of resistant isolates for these drugs was 19
      (76%), 4 (16%), 8 (32%), 6 (24%) and 1 (4%), respectively. CONCLUSIONS: The low
      sensitivity to CQ found here agrees with both in vitro and in vivo studies in
      Colombia. Ninety-six percent of the isolates were sensitive to AS. However, this
      study and previous reports have found isolates with low sensitivity to
      artemisinines (IC50>10.5 nM). This suggests that the indiscriminate use of these
      drugs put their efficacy at risk and eventually leave no options for falciparum
      malaria treatment.

PMID- 18719724
TI  - [Evaluation of the triflumuron and the mixture of Bacillus thuringiensis plus
      Bacillus sphaericus for control of the immature stages of Aedes aegypti and Culex
      quinquefasciatus (Diptera: Culicidae) in catch basins].
AB  - INTRODUCTION: In Cali, Colombia, catch basins (streetside storm drains) are one
      of the main larval habitats of Aedes aegypti and Culex quinquefasciatus. Since
      1999, these mosquitoes have been controlled by the Secretaria de Salud Municipal
      (Secretary of Municipal Public Health) using the larvicide triflumuron. Because
      of high densities of these mosquitoes that remain in the city, treatment failure
      was suspected -possibly insecticide resistance of the target species. OBJECTIVES:
      The efficacy of triflumuron and VectoMax (biorational mixture of Bacillus
      thuringiensis var. israelensis plus Bacillus sphaericus) were evaluated in the
      control of A. aegypti and C. quinquefasciatus in catch basins. The residual
      effect of a single application of the biorational formulation was determined in
      catch basins during periods of high and low rainfall. MATERIALS AND METHODS: The
      efficacy of the products was measured in 60 catch basins located in a residential
      neighborhood of Cali for a period of 90 days. The mean number of immature instars
      (A. aegypti and C. quinquefasciatus larvae and pupae of both species) was
      determined biweekly from 40 catch basins with insecticide intervention (20
      treated with triflumuron, 20 with VectoMax) and 20 untreated (control group). The
      residual effect of the biorational larvicide was evaluated biweekly in 10 catch
      basins during each of the 2 climatic periods. Results. The catch basins treated
      with VectoMax presented a significantly lower mean number of immature instars of
      both species compared with the control ( p<0.01). In contrast, the triflumuron
      treatment significantly reduced only immature instars of A. aegypti compared with
      the control ( p<0.001). The residual effect of VectoMax was higher during low
      rainfall compared to the control ( p<0.001). Conclusion. The biorational
      formulation was the more effective treatment for the control of both species
      during the period of evaluation (15 days).

PMID- 18719725
TI  - [Mosquitos (Diptera: Culicidae) in the small village where a human case of
      Venezuelan equine encephalitis was recorded].
AB  - INTRODUCTION: The enzootic focus of subtype ID of Venezuelan equine encephalitis
      (VEE) virus in the Central Magdalena region (central Colombia) occasionally
      produces human cases. The report of a VEE infection in a three-year-old girl in
      the small Chingale, municipalitype of Puerto Wilches, Santander, motivated this
      study. OBJECTIVE: The village of Chingale was evaluated as the probable site of
      infection. MATERIALS AND METHODS: In June 2005, mosquitoes were collected with
      CDC light traps in and outside of dwellings in the village. Trinidad traps were
      placed in nearby vegetation, and hamsters were used as sentinel animals near
      homes. RESULTS: One hundred and seven samples, consisting of 14,423 mosquitoes of
      35 species were collected. The relative abundance of incriminated vectors of
      subtype ID of VEE, Culex (Melanoconion) pedroi and Cx. (Mel.) ocossa, was
      generally low (<4%), but both species were more frequent outside of dwellings
      than indoors. Cx. (Mel.) ocossa was collected in CDC traps and was more frequent
      indoors,whereas Cx. (Mel.) pedroi was found in the Trinidad traps. In addition,
      Psorophora confinnis was present, recognized as a potential vector of the
      epidemo/epizootic subtype. Mansonia indubitans, another recognized vector, was
      present at high frequency within dwellings. The exposed hamsters did not become
      infected. CONCLUSION: The child may have been infected in or near her home,
      although the epidemiologic cycle of the virus was not demonstrated within the
      village of Chingale. Possibly, infected Culex mosquitoes of the subgenus
      Melanoconion carried the virus into the village from a neighboring habitat.

PMID- 18719726
TI  - [Resistance profiles to fluoroquinolones in clinical isolates of Gram positive
      cocci].
AB  - INTRODUCTION: Fluoroquinolones are broad spectrum antibiotics commonly used in
      the treatment of infections. OBJECTIVE: Resistance profiles of coccus bacteria to
      fluoroquinolones were evaluated in isolates of Streptococcus pneumoniae,
      Staphylococcus aureus, coagulase negative staphylococci and Enterococcus spp. The
      samples were recovered from Colombian hospitals between 1994 and 2004. MATERIALS
      AND METHODS: The minimal inhibitory concentration of ciprofloxacin, moxifloxacin
      and gatifloxacin was determined in 270 clinical isolates of S. pneumoniae, 348 of
      S. aureus, 176 of coagulase negative staphylococci and 123 of coagulase-negative
      enterococci. The minimal inhibitory concentration of levofloxacin was also
      determined in all isolates of methicillin-resistant S. aureus. An agar diffusion
      susceptibility test with disks of levofloxacin and ofloxacin was also applied to
      all isolates of S. pneumoniae. RESULTS: A total of 269 (99.6%) isolates of S.
      pneumoniae were susceptible to moxifloxacin and gatifloxacin. For levofloxacin
      and ofloxacin, resistance in S. pneumoniae was found in 1.5% and 8.9% of
      isolates, respectively. The ciprofloxacin minimal inhibitory concentration was >4
      microg/ml in 15.9% of pneumococcal isolates. The rates of resistance to
      ciprofloxacin, gatifloxacin and moxifloxacin in the 348 S. aureus isolates were
      55.4%, 54.9% and 52.6%, respectively; increasing to 92.3%, 91.3% and 87.5%,
      respectively in methicillin resistant isolates. Resistance to levofloxacin was
      found in 91.8% of MRSA isolates. The rates of resistance to ciprofloxacin,
      gatifloxacin and moxifloxacin in coagulase negative staphylococci and vancomycin
      susceptible enterococci were between 25.6% and 31.8%. All vancomycin-resistant
      enterococci were resistant to all fluroquinolones tested. CONCLUSION: The newer
      fluoroquinolones have maintained effective activity against clinical isolates of
      S. pneumoniae. The rates of fluoroquinolone resistance in S. aureus were very
      high, particularly in methicillin resistant isolates (approaching 100%).

PMID- 18719727
TI  - [Pediculosis prevalence and associated risk factors in a nursery school, Bogota,
      Colombia].
AB  - INTRODUCTION: Pediculosis is one of the most important chronic infestations in
      schoolchildren worldwide. Infestations show a high prevalence among the poorest
      children in developing countries, and it is associated with substandard hygienic
      practices. OBJECTIVE: The prevalence was estimated and seasonality described of a
      Pediculus infestation of seven months duration in a nursery school. Associations
      were explored among the standards of hygienic practices and hair characteristics.
      MATERIALS AND METHODS: One hundred and seventy-eight nursery school children
      between the ages of 3 months to 5 years, from the nursery school located at
      National University of Colombia, Bogota, were participants in the study. The
      children were examined for presence of Pediculus humanus infestation each month
      for seven months. The lengths and thicknesses of hair were measured at the first
      examination. A survey requesting information on socioeconomic and hygienic
      practices was provided to the caretakers of the children. Prevalence rates with
      95% confidence intervals were estimated for each explored association, and also
      to describe the differences of prevalences between age groups in each period.
      RESULTS: The highest prevalence was found in the children between the ages of 4
      and 5 years, at the beginning of the school year. A positive association was
      indicated between Pediculus infestation and hair longer than 11.5 cm [prevalence
      rate (PR)=2.0; 95% confidence interval (CI): 0.82-4.8], washing the hair less
      than three times a week (PR=1.58; 95%CI: 0.58-4.7), as well as sharing cleaning
      implements (PR=1.31; 95%CI: 38-4.46) and living with more than five people at
      home (PR=2.04; 95%CI: 0.8-5.06). Due to the limited size of the sample, none of
      the associations found were statistically significant. CONCLUSION: Pediculus
      infestation has a high prevalence in children of the nursery school studied. This
      infestation is associated with substandard hygienic practices, living with more
      than five people at home and the length of hair.

PMID- 18719728
TI  - [Concordance between thick blood smear, immunochromatography and polymerase chain
      reaction for malaria diagnosis].
AB  - INTRODUCTION: The rapid and effective diagnosis of malaria is the determining
      condition for an appropriate treatment and control of the disease. OBJECTIVE: The
      sensitivity, specificity and the positive and negative predictive values were
      evaluated in cases of suspected malaria in Colombia in a comparison of a rapid
      diagnostic test. the PCR test and the thick blood smear-the traditional gold
      standard. MATERIALS AND METHODS: A group of 100 patients with symptoms compatible
      with malaria, were included in the study. They were selected from the following
      Colombian regions: Uraba, Cordoba, lower Cauca, and relatively fewer from other
      malaria endemic areas of Colombia including the provinces of Valle, Choco in the
      central west of Colombia and Vichada to the east. To each patient the following
      three tests were performed: the rapid OptiMAL test, the PCR identification and
      the thick blood smear. The PCR amplified specific DNA sequences with primers
      designed to identify the genus Plasmodium, and the two species present in
      Colombia, P. falciparum and P. vivax. RESULTS: The sensitivity of the rapid test
      versus the thick smear, for the diagnosis of both species of Plasmodium was 93.9%
      (95% CI: 87-100%) and the specificity was 94.3% (95% CI:.253 85-100%). The PCR
      compared with the thick smear showed a sensitivity of 100% (95% CI: 99-100%) and
      a specificity of 97.1% (95% CI: 90-100%). CONCLUSIONS: The sensitivity and
      specificity of the three tests did not present statistically significant
      differences. However, the thick blood smear was recommended as the standard test,
      mainly due to its low cost.

PMID- 18719730
TI  - [Make your own diagnosis, second part].

PMID- 18719729
TI  - [Characterizing the CD3 epsilon chain from the New World primate Aotus
      nancymaae].
AB  - INTRODUCTION: The T-cell receptor (TCR)-associated complex, CD3 (d, g, e) and z
      chains are essential transmembrane proteins for signal transduction during T cell
      activation and immune response, as well as during thymocyte development.
      OBJECTIVE: This work established the CD3epsilon-chain primary structure for the
      New World owl monkey Aotus nancymaae. MATERIALS AND METHODS: Total RNA was
      isolated from peripheral blood mononuclear cells; CD3epsilon molecule was
      amplified, cloned and sequenced. RESULTS: The CD3epsilon amino acid sequence was
      deduced for the owl monkey Aotus nancymaae.> It has an identity for nucleotide
      and amino acid sequences with the human counterpart of 84% and 76%, respectively.
      As described in other species, the Aotus CD3-e molecule is very variable in the
      extracellular region and greatly conserved in the intracellular domain. Even
      though high variability occurs in the CD3epsilon-extracellular domain, the
      subregions involved in ectodomain folding are conserved. CONCLUSIONS: The primary
      structure suggested that the Aotus protein has a functional role similar to that
      of humans, and that the initial T-cell activation steps are also similar.
      However, the great variation observed in CD3epsilon-extracellular region in
      humans in contrast to the Aotus (especially in areas that are surface-exposed)
      indicated that some monoclonal antibodies against the human CD3 complex will not
      recognize these Aotus determinants.

PMID- 18719731
TI  - [In vitro effect of caffeine on internal mammary artery rings used in cardiac
      revascularization surgery].
AB  - INTRODUCTION: The vasodilator effect of caffeine in animal models arteries has
      been demonstrated previously. However, studies with the same methodology using
      human arteries in vitro have not been performed. OBJECTIVES: The in vitro
      vasoactive effects of caffeine was evaluated on human internal mammary arteries.
      MATERIALS AND METHODS: Internal mammary artery rings were used (n = 20).
      Endothelial function was evaluated with acetylcholine at a concentration of 3.16
      x 10 -6 M, nitroglycerine at cumulative concentrations of 10 -11 M to 10 -4 M and
      caffeine with cumulative concentrations of 10 -8 M to 10 -4 M. RESULTS:
      Nitroglycerin produced a maximum relaxation percentage of 87.4 +/- 12.3%,
      caffeine a percentage of 86.9 +/- 21.0% in arteries with functional endothelium,
      and of 71.6 +/- 28.6% in arteries with endothelial dysfunction. No differences
      were detected among the three groups ( p=0.289). Similarly, no differences were
      found between EC 50 in arteries with functional endothelium (1.66 x 10 -5 +/-1.57
      x 10 -5 M) and dysfunctional arteries (7.8 x 10 -5 +/-14.6 x 10 -5 M).
      Nitroglycerine proved more potent than caffeine (EC 50 = 4.3 x 10 -9 +/-4.4 x 10 
      9 M) ( p=0.013). CONCLUSIONS: Although nitroglycerin was a more potent
      vasodilator, caffeine had a strong arterial vasodilator effect regardless of
      endothelial function in human arteries.

PMID- 18719732
TI  - [Preliminary evaluation of maggot (Diptera: Calliphoridae) therapy as a potential
      treatment for leishmaniasis ulcers].
AB  - INTRODUCTION: Maggot debridement therapy has been widely used for treating a
      variety of scarred-over soft-tissue wounds. Published accounts record several
      illnesses in which treatment with larval therapy has promoted injury healing in
      conjunction with infection by bacterial pathogens resistant to conventional
      antibiotics. OBJECTIVE: An initial test of the maggot therapy was developed for
      cutaneous injuries produced by Leishmania amazonensis. MATERIALS AND METHODS: An
      experimental design based on an animal model with three replicates in
      Mesocricetus aureatus (Rodentia: Muridae) was used to evaluate size variation
      lesion before and after after larval therapy with Lucilia sericata maggots . The
      criteria used for therapy evaluation were lesion size, maggot application time,
      and presence or absence of edema and secretions. RESULTS: Effective scarring and
      wound healing was observed after therapy with L. sericata larvae, i.e. 80% to
      100% lesion area reduction after 12 hours. CONCLUSION: The preliminary results
      suggest that fly maggots of L. sericata have a potential use as natural medical
      and veterinary alternative therapy for the cutaneous leishmaniasis.

PMID- 18719733
TI  - Psychoactive drug advertising: content analysis.
AB  - The goal of this study was to describe the human figures portrayed in
      psychoactive drug advertising in terms of gender, age, ethnic group, and social
      context. Content analysis for 86 new pieces of printed advertisements released in
      2005 was carried out. Fisher exact test was used to analyze the association
      between categories. There was a preponderance of women (62.8%) who were four
      times more present in advertisements for antidepressants and anxyolitics than
      men. Most of the people shown were Caucasian (98.8%) young adults (72%). These
      people were pictured in leisure activities (46.5%), at home (29%), or in contact
      with nature (16.2%). The message conveyed was that the drugs treat routinely felt
      subjective symptoms of discomfort, inducing in an irrational appeal that may
      affect drug prescription.

PMID- 18719734
TI  - Utilization of the Family Health Program in metropolitan regions: a
      methodological approach.
AB  - OBJECTIVE: To present the methodological approach used to define the profile of
      health services utilization by the population enrolled in the Family Health
      Program. METHODS: Three patterns of services utilization accessed by the
      population were considered: residual, partial and full. These patterns were
      identified based on the range of actions of the Family Health Program that are
      accessed by the population. An enquiry was conducted in 2006 with two-stage
      sampling in an area characterized by high levels of social exclusion in the city
      of Sao Paulo, Brazil. In the first stage, 960 people participating in family
      health teams were drawn and classified by the community-based health agents as
      "full use" or not of the health services. In the second stage, 173 drawn subjects
      were then classified according to the patterns of services utilization. RESULTS:
      Subjects were classified as full users (16%), partial users (57%) and residual
      users (26%), and had different social and demographic characteristics. There was
      a selective and focused utilization of the services offered by the Family Health
      Program. Being male, having a level of schooling above the fifth grade of
      elementary school, having a paid job and accessing medical care systems implied
      lower adhesion to the services, even though the study focused on regions with few
      options of healthcare services. Even in areas of high social exclusion and low
      offer of health services, 25% of the enrolled population did not use the services
      offered at the Family Health Units, receiving only home visits. CONCLUSIONS:
      Methodologies that are capable of capturing distinct patterns of health services
      utilization by the population may contribute to improve services evaluation.

PMID- 18719735
TI  - Side effects of oxysterols: cytotoxicity, oxidation, inflammation, and
      phospholipidosis.
AB  - Oxysterols are 27-carbon atom molecules resulting from autoxidation or enzymatic
      oxidation of cholesterol. They are present in numerous foodstuffs and have been
      demonstrated to be present at increased levels in the plasma of patients with
      cardiovascular diseases and in atherosclerotic lesions. Thus, their role in lipid
      disorders is widely suspected, and they might also be involved in important
      degenerative diseases such as Alzheimer's disease, osteoporosis, and age-related
      macular degeneration. Since atherosclerosis is associated with the presence of
      apoptotic cells and with oxidative and inflammatory processes, the ability of
      some oxysterols, especially 7-ketocholesterol and 7beta-hydroxycholesterol, to
      trigger cell death, activate inflammation, and modulate lipid homeostasis is
      being extensively studied, especially in vitro. Thus, since there are a number of
      essential considerations regarding the physiological/pathophysiological functions
      and activities of the different oxysterols, it is important to determine their
      biological activities and identify their signaling pathways, when they are used
      either alone or as mixtures. Oxysterols may have cytotoxic, oxidative, and/or
      inflammatory effects, or none whatsoever. Moreover, a substantial accumulation of
      polar lipids in cytoplasmic multilamellar structures has been observed with
      cytotoxic oxysterols, suggesting that cytotoxic oxysterols are potent inducers of
      phospholipidosis. This basic knowledge about oxysterols contributes to a better
      understanding of the associated pathologies and may lead to new treatments and
      new drugs. Since oxysterols have a number of biological activities, and as
      oxysterol-induced cell death is assumed to take part in degenerative pathologies,
      the present review will focus on the cytotoxic activities of these compounds, the
      corresponding cell death signaling pathways, and associated events (oxidation,
      inflammation, and phospholipidosis).

PMID- 18719736
TI  - Role of the caudal pressor area in the regulation of sympathetic vasomotor tone.
AB  - It is well known that the ventrolateral medulla contains neurons involved in the
      tonic and reflex control of the cardiovascular system. Two regions within the
      ventrolateral medulla were initially identified: the rostral ventrolateral
      medulla (RVLM) and the caudal ventrolateral medulla (CVLM). Activation of the
      RVLM raises arterial blood pressure and sympathetic nerve activity, and
      activation of the CVLM causes opposite effects. The RVLM premotor neurons project
      directly to sympathetic preganglionic neurons and are involved in the maintenance
      of resting sympathetic vasomotor tone. A significant proportion of tonic activity
      in the RVLM sympathetic premotor neurons is driven by neurons located in a third
      region of the ventrolateral medulla denominated caudal pressor area (CPA). The
      CPA is a pressor region located at the extreme caudal part of the ventrolateral
      medulla that appears to have an important role controlling the activity of RVLM
      neurons. In this brief review, we will address the importance of the
      ventrolateral medulla neurons for the generation of resting sympathetic tone
      related to arterial blood pressure control focusing on two regions, the RVLM and
      the CPA.

PMID- 18719737
TI  - 13CO2 recovery fraction in expired air of septic patients under mechanical
      ventilation.
AB  - The continuous intravenous administration of isotopic bicarbonate (NaH13CO2) has
      been used for the determination of the retention of the 13CO2 fraction or the
      13CO2 recovered in expired air. This determination is important for the
      calculation of substrate oxidation. The aim of the present study was to evaluate,
      in critically ill patients with sepsis under mechanical ventilation, the 13CO2
      recovery fraction in expired air after continuous intravenous infusion of
      NaH13CO2 (3.8 micromol/kg diluted in 0.9% saline in ddH2O). A prospective study
      was conducted on 10 patients with septic shock between the second and fifth day
      of sepsis evolution (APACHE II, 25.9 +/- 7.4). Initially, baseline CO2 was
      collected and indirect calorimetry was also performed. A primer of 5 mL NaH13CO2
      was administered followed by continuous infusion of 5 mL/h for 6 h. Six CO2
      production (VCO2) measurements (30 min each) were made with a portable metabolic
      cart connected to a respirator and hourly samples of expired air were obtained
      using a 750-mL gas collecting bag attached to the outlet of the respirator. 13CO2
      enrichment in expired air was determined with a mass spectrometer. The patients
      presented a mean value of VCO2 of 182 +/- 52 mL/min during the steady-state
      phase. The mean recovery fraction was 0.68 +/- 0.06%, which is less than that
      reported in the literature (0.82 +/- 0.03%). This suggests that the 13CO2
      recovery fraction in septic patients following enteral feeding is incomplete,
      indicating retention of 13CO2 in the organism. The severity of septic shock in
      terms of the prognostic index APACHE II and the sepsis score was not associated
      with the 13CO2 recovery fraction in expired air.

PMID- 18719738
TI  - Low expression of APAF-1XL in acute myeloid leukemia may be associated with the
      failure of remission induction therapy.
AB  - Apoptotic protease activating factor 1 (APAF-1) has a critical role in the
      regulation of apoptosis. In the present study, the mRNA expression analysis of
      different APAF-1 transcripts (APAF-1S, APAF-1LC, APAF-1LN, and APAF-1XL) was
      analyzed in bone marrow samples from 37 patients with acute myeloid leukemia
      (newly diagnosed, with no previous treatment). APAF-1XL and APAF-1LN transcripts
      (with and without an extra WD-40 repeat region, respectively) were detected in
      all samples, although the major form expressed was APAF-1XL in 65% of the samples
      (group 1), while 35% of the samples expressed primarily APAF-1LN (group 2). Only
      46% of the patients presented complete remission in response to remission
      induction therapy (represented by less than 5% marrow blasts and hematological
      recovery), all but 2 cases being from group 1, 21.6% did not attain complete
      remission (only 1 case from group 1), and 32.4% of the patients died early. Lower
      expression of APAF-1XL (APAF-1XL/APAF-1LN ratio <1.2) was associated with a poor
      response to therapy (P = 0.0005, Fisher exact test). Both groups showed similar
      characteristics regarding white blood cell counts, cytogenetic data or presence
      of gene rearrangements associated with good prognosis as AML1-ETO, CBFB-MYH11 and
      PML/RARA. Since it has been shown that only the isoforms with the extra WD-40
      repeat region activate procaspase-9, we suggest that low procaspase-9 activation
      may also be involved in the deregulation of apoptosis and chemotherapy resistance
      in acute myeloid leukemia.

PMID- 18719739
TI  - p16INK4 expression in precursor lesions of squamous cell cervical cancer related
      to the presence of HPV-DNA.
AB  - The purpose of the present study was to identify the expression of p16INK4 in
      cervical cancer precursor lesions by immunohistochemistry and to correlate it
      with lesion grade and presence of human papillomavirus (HPV) infection. Cervical
      specimens from 144 women seen consecutively at the gynecology outpatient clinic
      of our institution from December 2003 to May 2005 were analyzed by cytopathology,
      histopathology, polymerase chain reaction for HPV-DNA, and p16INK4
      immunostaining. Histologically normal biopsies, HPV-DNA negative by polymerase
      chain reaction, were used as control. HPV-DNA prevalence, including the control
      group, was 68.1% and the prevalence of p16INK4 expression was 55.0%. The
      percentage of cells stained by p16INK4 ranged from 10 to 100%, both in the group
      consisting of cervical intraepithelial neoplasia (CIN)1/HPV specimens and in the
      group of CIN2/CIN3 specimens with P value of 0.0001. p16INK4 expression was 48.3%
      in the CIN1/HPV group, as opposed to 94.3% in the CIN2/CIN3 group (P = 0.001),
      showing a statistically significant difference between the two groups. The
      quantitative method used here is simple and less subjective than the different
      semiquantitative methods described in the literature. In view of the different
      definitions of a p16INK4-positive case, it is almost impossible to compare the
      findings reported by different investigators. This study confirms the association
      between p16INK4 and CIN2 and CIN3 lesions. Moreover, it shows that some low grade
      lesions expressed high levels of this protein. This may indicate that such low
      grade lesions may be predisposed to progress to high grade lesions. This means
      that p16INK4 may be a strong marker for "neoplastic lesions" induced by HPV and
      not just an infection marker.

PMID- 18719740
TI  - Spectroscopic studies on the interaction of efonidipine with bovine serum
      albumin.
AB  - Efonidipine hydrochloride is an antihypertensive and antianginal agent with fewer
      side effects and is better tolerated in the treatment of hypertension with renal
      impairment. Its interaction with bovine serum albumin (BSA) is of great use for
      the understanding of the pharmacokinetic and pharmacodynamic mechanisms of the
      drug. The binding of efonidipine to BSA was investigated by fluorescence
      spectroscopy and circular dichroism. BSA fluorescence was quenched by
      efonidipine, due to the fact that efonidipine quenched the fluorescence of
      tryptophan residues mainly by the collision mode. The thermodynamic parameters
      DeltaH0 and DeltaS0 were 68.04 kJ/mol and 319.42 J x mol-1 x K-1, respectively,
      indicating that the hydrophobic interactions played a major role. The results of
      circular dichroism and synchronous fluorescence measurements showed that the
      binding of efonidipine to BSA led to a conformational change of BSA. The fraction
      of occupied sites (theta) for the 8-anilino-1-naphthalein-sulfonic acid (ANS)-BSA
      system is 85%, whereas for the NZ-105-BSA system, it is 53%, which suggests that
      the interaction of ANS with BSA is stronger than that of NZ-105 with BSA. Binding
      studies in the presence of ANS indicated that efonidipine competed with ANS for
      hydrophobic sites of BSA. The effects of metal ions on the binding constant of
      the efonidipine-BSA complex were also investigated. The presence of metal ions
      Zn2+, Mg2+, Al3+, K+, and Ca2+ increased the binding constant of efonidipine-BSA
      complex, which may prolong the storage period of NZ-105 in blood plasma and
      enhance its maximum effects.

PMID- 18719741
TI  - Expression of a hantavirus N protein and its efficacy as antigen in immune
      assays.
AB  - Hantavirus cardiopulmonary syndrome (HCPS) has been recognized as an important
      public heath problem. Five hantaviruses associated with HCPS are currently known
      in Brazil: Juquitiba, Araraquara, Laguna Negra-like, Castelo dos Sonhos, and
      Anajatuba viruses. The laboratory diagnosis of HCPS is routinely carried out by
      the detection of anti-hantavirus IgM and/or IgG antibodies. The present study
      describes the expression of the N protein of a hantavirus detected in the blood
      sample of an HCPS patient. The entire S segment of the virus was amplified and
      found to be 1858 nucleotides long, with an open reading frame of 1287 nucleotides
      that encodes a protein of 429 amino acids. The nucleotide sequence described here
      showed a high identity with the N protein gene of Araraquara virus. The entire N
      protein was expressed using the vector pET200D and the Escherichia coli BL21
      strain. The expression of the recombinant protein was confirmed by the detection
      of a 52-kDa protein by Western blot using a pool of human sera obtained from HCPS
      patients, and by specific IgG detection in five serum samples of HCPS patients
      tested by ELISA. These results suggest that the recombinant N protein could be
      used as an antigen for the serological screening of hantavirus infection.

PMID- 18719742
TI  - Characterization of rat heart alkaline phosphatase isoenzymes and modulation of
      activity.
AB  - Alkaline phosphatase (ALP) is important in calcification and its expression seems
      to be associated with the inflammatory process. We investigated the in vitro
      acute effects of compounds used for the prevention or treatment of cardiovascular
      diseases on total ALP activity from male Wistar rat heart homogenate. ALP
      activity was determined by quantifying, at 410 nm, the p-nitrophenol released
      from p-nitrophenylphosphate (substrate in Tris buffer, pH 10.4). Using specific
      inhibitors of ALP activity and the reverse transcription-polymerase chain
      reaction, we showed that the rat heart had high ALP activity (31.73 +/- 3.43 nmol
      p-nitrophenol.mg protein-1.min-1): mainly tissue-nonspecific ALP but also tissue
      specific intestinal ALP type II. Both ALP isoenzymes presented myocardial
      localization (striated pattern) by immunofluorescence. ALP was inhibited a)
      strongly by 0.5 mM levamisole, 2 mM theophylline and 2 mM aspirin (91, 77 and
      84%, respectively) and b) less strongly by 2 mM L-phenylalanine, 100 mL
      polyphenol-rich beverages and 0.5 mM progesterone (24, 21 to 29 and 11%,
      respectively). beta-estradiol and caffeine (0.5 and 2 mM) had no effect; 0.5 mM
      simvastatin and 2 mM atenolol activated ALP (32 and 36%, respectively).
      Propranolol (2 mM) tended to activate ALP activity and corticosterone activated
      (18%) and inhibited (13%) (0.5 and 2 mM, respectively). We report, for the first
      time, that the rat heart expresses intestinal ALP type II and has high total ALP
      activity. ALP activity was inhibited by compounds used in the prevention of
      cardiovascular pathology. ALP manipulation in vivo may constitute an additional
      target for intervention in cardiovascular diseases.

PMID- 18719743
TI  - Association of loss of heterozygosity with cytogenetic abnormalities in acute
      myeloid leukemia and myelodysplastic syndrome.
AB  - Deletions on chromosomes 5 and 7 are frequently seen in myelodysplastic syndrome
      (MDS) and acute myeloid leukemia (AML). It is assumed that these deletions
      indicate loss of tumor suppressor genes on these chromosomes and until these
      tumor suppressor genes are identified, the functional consequences of these
      deletions and the molecular basis of these myeloid disorders cannot be completely
      understood. We evaluated loss of heterozygosity (LOH) in 44 patients (18 MDS and
      26 AML, diagnosed according to WHO classification criteria) at diagnosis, using a
      four-microsatellite marker panel: an intragenic marker on the 7th intron of gene
      IRF-1 of the 5q31.1 region and three markers located inside the 7q31.1 region and
      correlated the LOH with karyotype abnormalities. The microsatellites chosen
      corresponded to chromosome regions frequently deleted in MDS/AML. The samples
      with Q (peak area) less than or equal to 0.50 were indicative of LOH. The percent
      of informative samples (i.e., heterozygous) for the intragenic microsatellite in
      gene IRF-1 and in loci D7S486, D7S515 and D7S522 were 66.6, 73.7, 75.5, and
      48.8%, respectively. Cytogenetic abnormalities by G-banding were found in 36%
      (16/44) of the patients (2 of 18 MDS and 14 of 26 AML patients). We found a
      significantly positive association of the occurrence of LOH with abnormal
      karyotype (P < 0.05; chi-square test) and there were cases with LOH but the
      karyotype was normal (by G-banding). These data indicate that LOH in different
      microsatellite markers is possibly an event previous to chromosomal abnormalities
      in these myeloid neoplasias.

PMID- 18719744
TI  - Obesity induces upregulation of genes involved in myocardial Ca2+ handling.
AB  - Obesity is a complex multifactorial disorder that is often associated with
      cardiovascular diseases. Research on experimental models has suggested that
      cardiac dysfunction in obesity might be related to alterations in myocardial
      intracellular calcium (Ca2+) handling. However, information about the expression
      of Ca2+-related genes that lead to this abnormality is scarce. We evaluated the
      effects of obesity induced by a high-fat diet in the expression of Ca2+-related
      genes, focusing the L-type Ca2+ channel (Cacna1c), sarcolemmal Na+/Ca2+ exchanger
      (NCX), sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ryanodine receptor (RyR2),
      and phospholamban (PLB) mRNA in rat myocardium. Male 30-day-old Wistar rats were
      fed a standard (control) or high-fat diet (obese) for 15 weeks. Obesity was
      defined as increased percent of body fat in carcass. The mRNA expression of Ca2+
      related genes in the left ventricle was measured by RT-PCR. Compared with control
      rats, the obese rats had increased percent of body fat, area under the curve for
      glucose, and leptin and insulin plasma concentrations. Obesity also caused an
      increase in the levels of SERCA2a, RyR2 and PLB mRNA (P < 0.05) but did not
      modify the mRNA levels of Cacna1c and NCX. These findings show that obesity
      induced by high-fat diet causes cardiac upregulation of Ca2+ transport_related
      genes in the sarcoplasmic reticulum.

PMID- 18719745
TI  - Moderate-term reproducibility of heart rate variability during rest and light to
      moderate exercise in children.
AB  - Previous studies have demonstrated the high reproducibility of heart rate
      variability (HRV) measures in adults while little information exists concerning
      HRV reproducibility in children. Subsequently, the aim of the current study was
      to examine the moderate-term reproducibility of heart rate and frequency domain
      measures of HRV during rest and light to moderate exercise in children. Ten
      healthy children (6 males, 4 females) aged between 7 and 12 years of age
      volunteered for this study with HRV recordings obtained during supine rest and
      three treadmill walking exercise work rates (< or =60% maximum heart rate),
      initially and then 8 weeks later. Differences (P < 0.05) between variables were
      examined using paired t-tests or Wilcoxon signed rank tests while reliability and
      reproducibility were examined by intraclass correlation coefficients (ICC),
      coefficients of variation (CV), and mean bias ratio and ratio limits of agreement
      (LOA). Heart rate and all measures of HRV at rest and exercise were unchanged
      after 8 weeks. Significant ICC were documented primarily during rest (0.72-0.85)
      while weaker relationships (-0.02-0.87) were evident during exercise. A large
      range of CV was identified during rest (6-33%) and exercise (3-128%) while the
      ratio LOA were variable and substantial (1.04-2.73). Despite similar HRV over an
      8-week period, variable ICC and sizable CV and ratio LOA indicate moderate to
      poor reproducibility of HRV in children, particularly during light to moderate
      exercise. Studies examining HRV in children should include age- or maturation
      stage-matched control participants to address the age-related change in HRV and
      inadequate HRV reliability.

PMID- 18719746
TI  - Comparison of the effects of lactated Ringer solution with and without
      hydroxyethyl starch fluid resuscitation on gut edema during severe splanchnic
      ischemia.
AB  - The type of fluid used during resuscitation may have an important impact on
      tissue edema. We evaluated the impact of two different regimens of fluid
      resuscitation on hemodynamics and on lung and intestinal edema during splanchnic
      hypoperfusion in rabbits. The study included 16 female New Zealand rabbits (2.9
      to 3.3 kg body weight, aged 8 to 12 months) with splanchnic ischemia induced by
      ligation of the superior mesenteric artery. The animals were randomized into two
      experimental groups: group I (N = 9) received 12 mL x kg-1 x h-1 lactated Ringer
      solution and 20 mL/kg 6% hydroxyethyl starch solution; group II (N = 7) received
      36 mL x kg-1 x h-1 lactated Ringer solution and 20 mL/kg 0.9% saline. A segment
      from the ileum was isolated to be perfused. A tonometric catheter was placed in a
      second gut segment. Superior mesenteric artery (Q SMA) and aortic (Qaorta) flows
      were measured using ultrasonic flow probes. After 4 h of fluid resuscitation,
      tissue specimens were immediately removed for estimations of gut and lung edema.
      There were no differences in global and regional perfusion variables, lung wet-to
      dry weight ratios and oxygenation indices between groups. Gut wet-to-dry weight
      ratio was significantly lower in the crystalloid/colloid-treated group (4.9 +/-
      1.5) than in the crystalloid-treated group (7.3 +/- 2.4) (P < 0.05). In this
      model of intestinal ischemia, fluid resuscitation with crystalloids caused more
      gut edema than a combination of crystalloids and colloids.

PMID- 18719749
TI  - Efficacy and safety of trabeculectomy with mitomycin C for childhood glaucoma: a
      study of results with long-term follow-up.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of trabeculectomy with
      mitomycin C in the management of childhood glaucoma. INTRODUCTION: The use of
      antifibrotic agents enhances the success of trabeculectomy performed in both
      adults and children. METHODS: A retrospective chart review (1991-2001) of 114
      patients (114 eyes) from 0-14 years of age with congenital or developmental
      glaucoma. These patients underwent trabeculectomy with mitomycin but had not been
      previously treated with any antifibrotic agent. RESULTS: The mean patient age was
      57.36+/-51.14 months (range: 0.5-168 months). Treatment was considered successful
      in 63 eyes (55.26%), with a mean intraocular pressure of 12.11+/-3.98 mmHg. For
      patients categorized as successfully treated, the mean follow-up time was 61.16+/
      26.13 months (range 12-113 months). A post-surgical intraocular pressure of <16
      was observed in 47 eyes. The life-table success rates for intraocular pressure
      control at 24, 36, 48, and 60 months were 90.2%, 78.7%, 60.7% and 50.8%,
      respectively. The cumulative probability of failure was 40.8% at 12 months.
      Following surgery, endophthalmitis appeared in eight eyes (4.88%) after an
      average 36.96 months (range: 1.7-106 months). Other complications included
      expulsive hemorrhage, flat anterior chamber and bleb leak. DISCUSSION: It has
      been reported in pediatric patients that trabeculectomy without adjunctive
      antimetabolites achieves a successful outcome in 30% to 50% of cases. In our
      study, treatment was considered successful in 63 eyes (55.26%) within 61.16+/
      26.13 months of follow-up. CONCLUSIONS: Trabeculectomy with mitomycin is safe and
      effective for short-term or long-term treatment of congenital or developmental
      glaucoma. The frequency of bleb-related endophthalmitis was no higher in these
      patients than that described in adults.

PMID- 18719750
TI  - High ratio of triglycerides to HDL-cholesterol predicts extensive coronary
      disease.
AB  - An abnormal ratio of triglycerides to HDL-cholesterol (TG/HDL-c) indicates an
      atherogenic lipid profile and a risk for the development of coronary disease.
      OBJECTIVE: To investigate the association between lipid levels, specifically
      TG/HDL-c, and the extent of coronary disease. METHODS: High-risk patients (n=374)
      submitted for coronary angiography had their lipid variables measured and
      coronary disease extent scored by the Friesinger index. RESULTS: The subjects
      consisted of 220 males and 154 females, age 57.2+/-11.1 years, with total
      cholesterol of 210+/-50.3 mg/dL, triglycerides of 173.8+/-169.8 mg/dL, HDL
      cholesterol (HDL-c) of 40.1+/-12.8 mg/dL, LDL-cholesterol (LDL-c) of 137.3+/-46.2
      mg/dL, TG/HDL-c of 5.1+/-5.3, and a Friesinger index of 6.6+/-4.7. The
      relationship between the extent of coronary disease (dichotomized by a Friesenger
      index of 5 and lipid levels (normal vs. abnormal) was statistically significant
      for the following: triglycerides, odds ratio of 2.02 (1.31-3.1; p=0.0018); HDL-c,
      odds ratio of 2.21 (1.42-3.43; p=0.0005); and TG/HDL-c, odds ratio of 2.01(1.30
      3.09; p=0.0018). However, the relationship was not significant between extent of
      coronary disease and total cholesterol [1.25 (0.82-1.91; p=0.33)] or LDL-c [1.47
      (0.96-2.25; p=0.0842)]. The chi-square for linear trends for Friesinger >4 and
      lipid quartiles was statistically significant for triglycerides (p=0.0017), HDL-c
      (p=0.0001), and TG/HDL-c (p=0.0018), but not for total cholesterol (p=0.393) or
      LDL-c (p=0.0568). The multivariate analysis by logistic regression OR gave 1.3+/
      0.79 (p= .0001) for TG/HDL-c, 0.779+/-0.074 (p= .0001) for HDL-c, and 1.234+/
      0.097 (p=0.03) for LDL. Analysis of receiver operating characteristic curves
      showed that only TG/HDL-c and HDL-c were useful for detecting extensive coronary
      disease, with the former more strongly associated with disease. CONCLUSIONS:
      Although some lipid variables were associated with the extent of coronary
      disease, the ratio of triglycerides to HDL-cholesterol showed the strongest
      association with extent.

PMID- 18719751
TI  - Correlation between the water drinking test and modified diurnal tension curve in
      untreated glaucomatous eyes.
AB  - OBJECTIVES: To investigate the correlation and agreement between the intraocular
      pressure peaks detected during the water drinking test and the modified diurnal
      tension curve in untreated glaucomatous eyes. INTRODUCTION: It has been suggested
      that the intraocular pressure peaks detected during the water drinking test
      predict the peaks observed during a 24-hour diurnal tension curve. A more
      feasible and practical test for assessing intraocular pressure peaks in
      glaucomatous eyes during office hours would be of great clinical utility.
      METHODS: This was a prospective study involving open angle glaucoma patients
      without anti-glaucoma medication submitted to the modified diurnal tension curve
      and water drinking test on the same day. The intraocular pressure peaks during
      the water drinking test and the modified diurnal tension curve were reported and
      compared. Statistical analysis was performed to assess the correlation and
      agreement between intraocular pressure peak measurements. RESULTS: The
      correlation between intraocular pressure peaks during the water drinking test and
      modified diurnal tension curve was significant and strong (Pearson's Correlation
      Coefficient r=0.780, p<0.0001). Limited agreement was observed between these
      measurements. Eighty-two percent of intraocular pressure peaks were higher during
      the water drinking test than the modified diurnal tension curve. DISCUSSION:
      These findings suggest that the water drinking test may be used as tool to assess
      risk factors for glaucomatous patients. CONCLUSION: Intraocular pressure peaks
      detected during the water drinking test could be used in clinical practice to
      both estimate the peaks observed during the modified diurnal tension curve and
      assess the status of the eye's outflow facility.

PMID- 18719752
TI  - Physical exercise improves the functional capacity and quality of life in
      patients with heart failure.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of physical
      exercise on the functional capacity and quality of life in heart failure
      patients. METHODS: Forty-two patients of both sexes with heart failure of NYHA
      class II and III with different etiologies were randomly divided into untrained
      or trained groups. The six-month exercise program consisted of aerobic training,
      muscle strength training, agility and joint flexibility activities. Physical
      fitness was evaluated by testing the performance on these trained components.
      Quality of life was evaluated by scored answers to a standardized questionnaire
      involving multiple domains. RESULTS: Baseline values did not differ between
      groups. Improvement in the trained group was identified in all components of
      functional capacity when compared to the untrained group (p<0.001). Quality of
      life improved in the trained patients concerning physical, psychological, social
      and environmental domains (p<0.001), whereas no significant change was found in
      the untrained patients. CONCLUSIONS: Guided and monitored physical exercise is
      safe and has the potential to improve functional capacity and quality of life in
      heart failure patients with multiple etiologies.

PMID- 18719753
TI  - Knee joint dysfunctions that influence gait in cerebrovascular injury.
AB  - INTRODUCTION: There is still no consensus among different specialists on the
      subject of kinematic variation during the hemiparetic gait, including the main
      changes that take place during the gait cycle and whether the gait velocity
      changes the patterns of joint mobility. One of the most frequently discussed
      joints is the knee. OBJECTIVES: This study aims to evaluate the variables found
      in the angular kinematics of knee joint, and to describe the alterations found in
      the hemiparetic gait resulting from cerebrovascular injury. METHODS: This study
      included 66 adult patients of both genders with a diagnosis of either right or
      left hemiparesis resulting from ischemic cerebrovascular injury. All the
      participants underwent three-dimensional gait evaluation, an the angular
      kinematics of the joint knee were selected for analysis. RESULTS: The results
      were distributed into four groups formed based on the median of the gait speed
      and the side of hemiparesis. CONCLUSIONS: The relevant clinical characteristics
      included the important mechanisms of loading response in the stance, knee
      hyperextension in single stance, and reduction of the peak flexion and movement
      amplitude of the knee in the swing phase. These mechanisms should be taken into
      account when choosing the best treatment. We believe that the findings presented
      here may aid in preventing the occurrence of the problems found, and also in
      identifying the origin of these problems.

PMID- 18719754
TI  - DNA sequencing confirms the involvement of Leishmania (L.) amazonensis in
      American tegumentary leishmaniasis in the state of Sao Paulo, Brazil.
AB  - INTRODUCTION: American tegumentary leishmaniasis (ATL) represents one of the most
      important public health issues in the world. An increased number of autochthonous
      cases of ATL in the Northeastern region of Sao Paulo State has been documented in
      the last few years, leading to a desire to determine the Leishmania species
      implicated. METHODS: PCR followed by DNA sequencing was carried out to identify a
      120bp fragment from the universal kDNA minicircle of the genus Leishmania in 61
      skin or mucosal biopsies from patients with ATL. RESULTS: DNA sequencing
      permitted the identification of a particular 15bp fragment (5' GTC TTT GGG GCA
      AGT... 3') in all samples. Analysis by the neighbor-joining method showed the
      occurrence of two distinct groups related to the genus Viannia (V) and Leishmania
      (L), each with two subgroups. Autochthonous cases with identity to a special
      Leishmania sequence not referenced in Genbank predominated in subgroup V.1,
      suggesting the possible existence of a subtype or mutation of Leishmania Viannia
      in this region. In the subgroup L.2, which showed identity with a known sequence
      of L. (L.) amazonensis, there was a balanced distribution of autochthonous and
      non-autochthonous cases, including the mucosal and mucocutaneous forms in four
      patients. The last observation may direct us to new concepts, since the mucosal
      compromising has commonly been attributed to L. (V.) braziliensis, even though L.
      (L.) amazonensis is more frequent in the Amazonian region. CONCLUSIONS: These
      results confirm the pattern of distribution and possible mutations of these
      species, as well as the change in the clinical form presentation of ATL in the
      Sao Paulo State.

PMID- 18719755
TI  - Epidemiology of severe sepsis in the emergency department and difficulties in the
      initial assistance.
AB  - BACKGROUND: The aim of this study was to determine the occurrence rate,
      demographics, clinical characteristics, and outcomes of patients with severe
      sepsis admitted to the emergency department. METHODS: A prospective study
      evaluating all patients admitted to the emergency department unit in a public
      hospital of tertiary complexity in a six-month period was conducted. During this
      period, the emergency team was trained to diagnose sepsis. Patients who met the
      diagnostic criteria for severe sepsis were followed until their discharge from
      the hospital. RESULTS: A total of 5,332 patients were admitted to the emergency
      department, and 342 met the criteria for severe sepsis/septic shock. The median
      (interquartile range) age of patients was 74 (65-84) years, and 52.1% were male.
      The median APACHE II and SOFA scores at diagnosis were 19 (15-25) and 5 (3-7),
      respectively. The median number of dysfunctional organ systems per patient was 2
      (1-3). The median hospital length of stay was 10 (4.7-17) days, and the hospital
      mortality rate was 64%. Only 31% of the patients were diagnosed by the emergency
      department team as septic. About 33.5% of the 342 severe sepsis patients admitted
      to the emergency department were referred to an ICU, with a median time delay of
      24 (12-48) hours. Training improved diagnosis and decreased the time delay for
      septic patients in arriving at the ICU. CONCLUSIONS: The occurrence rate of
      severe sepsis in the emergency department was 6.4%, and the rate of sepsis
      diagnosed by the emergency department team as well as the number of patients
      transferred to the ICU was very low. Educational campaigns are important to
      improve diagnosis and, hence, treatment of severe sepsis.

PMID- 18719756
TI  - Single-blind, randomized, controlled trial of pelvic floor muscle training,
      electrical stimulation, vaginal cones, and no active treatment in the management
      of stress urinary incontinence.
AB  - PURPOSE: To compare the effectiveness of pelvic floor exercises, electrical
      stimulation, vaginal cones, and no active treatment in women with urodynamic
      stress urinary incontinence. PATIENTS AND METHODS: One hundred eighteen subjects
      were randomly selected to receive pelvic floor exercises (n=31), ES (n=30),
      vaginal cones (n=27), or no treatment (untreated control) (n=30). Women were
      evaluated before and after completion of six months of treatment by the pad test,
      quality of life questionnaire (I-QOL), urodynamic test, voiding diary, and
      subjective response. RESULTS: In the objective evaluation, we observed a
      statistically significant reduction in the pad test (p=0.003), in the number of
      stress urinary episodes (p<0.001), and a significant improvement in the quality
      of life (p<0.001) in subjects who used pelvic floor exercises, electrical
      stimulation, and vaginal cones compared to the control group. No significant
      difference was found between groups in the urodynamic parameters. In the
      subjective evaluation, 58%, 55%, and 54% of women who had used pelvic floor
      exercises, electrical stimulation, and vaginal cones, respectively, reported
      being satisfied after treatment. In the control group, only 21% patients were
      satisfied with the treatment. CONCLUSION: Based on this study, pelvic floor
      exercises, electrical stimulation, and vaginal cones are equally effective
      treatments and are far superior to no treatment in women with urodynamic stress
      urinary incontinence.

PMID- 18719757
TI  - Evaluation of physical activity habits in patients with posttraumatic stress
      disorder.
AB  - OBJECTIVE: In this study, we present data from a survey that aimed to assess the
      physical activity habits of adult Brazilian patients with Posttraumatic Stress
      Disorder. METHOD: Fifty male and female patients with Posttraumatic Stress
      Disorder participated in this study. The mean age at onset was 37+/-12 years, and
      the mean time between diagnosis and follow-up was 3.6+/-4.2 years. RESULTS:
      Substantial changes in physical activity habits were observed following the onset
      of PTSD. While more than half of the patients participated in physical activities
      prior to Posttraumatic Stress Disorder onset, there was a significant reduction
      in their participation afterwards. The justifications for stopping physical
      activities or sport participation were lack of time and lack of motivation.
      DISCUSSION: Several studies have shown that physical exercise decreases reverts
      symptoms of psychiatric disorders such as depression, anxiety and social
      isolation. We could therefore hypothesize that patients with Posttraumatic Stress
      Disorder who exercise should experience the same benefits. CONCLUSION: Our
      findings demonstrated that patients with Posttraumatic Stress Disorder have low
      levels of participation in sports or physical activities.

PMID- 18719758
TI  - Heart rate dynamics during a treadmill cardiopulmonary exercise test in optimized
      beta-blocked heart failure patients.
AB  - BACKGROUND: Calculating the maximum heart rate for age is one method to
      characterize the maximum effort of an individual. Although this method is
      commonly used, little is known about heart rate dynamics in optimized beta
      blocked heart failure patients. AIM: The aim of this study was to evaluate heart
      rate dynamics (basal, peak and % heart rate increase) in optimized beta-blocked
      heart failure patients compared to sedentary, normal individuals (controls)
      during a treadmill cardiopulmonary exercise test. METHODS: Twenty-five heart
      failure patients (49+/-11 years, 76% male), with an average LVEF of 30+/-7%, and
      fourteen controls were included in the study. Patients with atrial fibrillation,
      a pacemaker or noncardiovascular functional limitations or whose drug therapy was
      not optimized were excluded. Optimization was considered to be 50 mg/day or more
      of carvedilol, with a basal heart rate between 50 to 60 bpm that was maintained
      for 3 months. RESULTS: Basal heart rate was lower in heart failure patients (57+/
      3 bpm) compared to controls (89+/-14 bpm; p<0.0001). Similarly, the peak heart
      rate (% maximum predicted for age) was lower in HF patients (65.4+/-11.1%)
      compared to controls (98.6+/-2.2; p<0.0001). Maximum respiratory exchange ratio
      did not differ between the groups (1.2+/-0.5 for controls and 1.15+/-1 for heart
      failure patients; p=0.42). All controls reached the maximum heart rate for their
      age, while no patients in the heart failure group reached the maximum. Moreover,
      the % increase of heart rate from rest to peak exercise between heart failure
      (48+/-9%) and control (53+/-8%) was not different (p=0.157). CONCLUSION: No
      patient in the heart failure group reached the maximum heart rate for their age
      during a treadmill cardiopulmonary exercise test, despite the fact that the
      percentage increase of heart rate was similar to sedentary normal subjects. A
      heart rate increase in optimized beta-blocked heart failure patients during
      cardiopulmonary exercise test over 65% of the maximum age-adjusted value should
      be considered an effort near the maximum. This information may be useful in
      rehabilitation programs and ischemic tests, although further studies are
      required.

PMID- 18719759
TI  - The impact of duration of organ dysfunction on the outcome of patients with
      severe sepsis and septic shock.
AB  - OBJECTIVES: This study aimed to assess the impact of the duration of organ
      dysfunction on the outcome of patients with severe sepsis or septic shock.
      METHODS: Clinical data were collected from hospital charts of patients with
      severe sepsis and septic shock admitted to a mixed intensive care unit from
      November 2003 to February 2004. The duration of organ dysfunction prior to
      diagnosis was correlated with mortality. Results were considered significant if
      p<0.05. RESULTS: Fifty-six patients were enrolled. Mean age was 55.6+/-20.7
      years, mean APACHE II score was 20.6+/-6.9, and mean SOFA score was 7.9+/-3.7.
      Thirty-six patients (64.3%) had septic shock. The mean duration of organ
      dysfunction was 1.9+/-1.9 days. Within the univariate analysis, the variables
      correlated with hospital mortality were: age (p=0.015), APACHE II (p=0.008),
      onset outside the intensive care unit (p=0.05), blood glucose control (p=0.05)
      and duration of organ dysfunction (p=0.0004). In the multivariate analysis, only
      a duration of organ dysfunction persisting longer than 48 hours correlated with
      mortality (p=0.004, OR: 8.73 (2.37-32.14)), whereas the APACHE II score remained
      only a slightly significant factor (p=0.049, OR: 1.11 (1.00-1.23)). Patients who
      received therapeutic interventions within the first 48 hours after the onset of
      organ dysfunction exhibited lower mortality (32.1% vs. 82.1%, p=0.0001).
      CONCLUSIONS: These findings suggest that the diagnosis of organ dysfunction is
      not being made in a timely manner. The time elapsed between the onset of organ
      dysfunction and initiation of therapeutic intervention can be quite long, and
      this represents an important determinant of survival in cases of severe sepsis
      and septic shock.

PMID- 18719760
TI  - Transdisciplinary approach to the follow-up of patients after myocardial
      infarction.
AB  - OBJECTIVES: To compare conventional and transdisciplinary care in a tertiary
      outpatient clinic for patients after their first acute myocardial infarction.
      METHODS: One hundred fifty-three patients with acute myocardial infarction were
      randomized at hospital discharge and followed-up to compare conventional (n=75)
      and transdisciplinary care (n=78). They were submitted to a clinical evaluation,
      received a dietary plan, and were re-evaluated twice in 60-180 days by a nurse,
      dietitian and physician, when new clinical and laboratory data were collected.
      The primary outcome was clinical improvement, as evaluated by an index including
      reduction of body weight, lowering of blood pressure, smoking cessation, increase
      in physical activity and compliance with medication. RESULTS: The groups were
      similar at baseline: 63.4% were men, 89.9% had an acute myocardial infarction
      with ST-segment-elevation, 32.7% were diabetic, and 72.2% were hypertensive. The
      clinical improvement index was similar between the studied groups: in 33.3 %
      (transdisciplinary care) vs. 30.4 % (conventional care) of patients, the
      improvement was very good (P=1.000). Rates of re-hospitalization and death
      (p=0.127) were similar between transdisciplinary and conventional care.
      Compliance with diet was higher for transdisciplinary care (50.0%) vs.
      conventional care (26.1%) (p=0.007), as was compliance with visits (73.3 vs.
      40.3%, respectively, p<0.001). CONCLUSIONS: Compliance with diet and visits was
      higher for transdisciplinary care vs. conventional care; however, the
      transdisciplinary approach did not provide more clinical benefits than the
      conventional approach after patients' first acute myocardial infarction in this
      setting.

PMID- 18719761
TI  - Post-mortem histological pulmonary analysis in patients with HIV/AIDS.
AB  - OBJECTIVES: Certain aspects of pulmonary pathology observed in autopsies of
      HIV/AIDS patients are still unknown. This study considers 250 autopsies of
      HIV/AIDS patients who died of acute respiratory failure and describes the
      demographic data, etiology, and histological pulmonary findings of the various
      pathologies. METHODS: The following data were obtained: age, sex, and major
      associated diseases (found at the autopsy). Pulmonary histopathology was
      categorized as: diffuse alveolar damage; pulmonary edema; alveolar hemorrhage;
      and acute interstitial pneumonia. Odds ratio of the HIV/AIDS-associated diseases
      developing a specific histopathological pattern was determined by logistic
      regression. RESULTS: A total of 197 men and 53 women were studied. The mean age
      was 36 years. Bacterial bronchopneumonia was present in 36% (91 cases) and
      Pneumocystis jiroveci pneumonia in 27% (68) of patients. Pulmonary histopathology
      showed acute interstitial pneumonia in 40% (99), diffuse alveolar damage in 36%
      (89), pulmonary edema in 13% (33), and alveolar hemorrhage in 12% (29) of
      patients. Multivariate analysis showed a significant and positive association
      between Pneumocystis jiroveci pneumonia and acute interstitial pneumonia (Odds
      ratio, 4.51; 95% CI, 2.46-8.24; p<0.001), severe sepsis and/or septic shock and
      diffuse alveolar damage (Odds ratio, 3.60; 95% CI, 1.78-7.27; p<0.001), and
      cytomegalovirus and acute interstitial pneumonia (Odds ratio, 2.22; 95% CI, 1.01
      4.93; p=0.05). CONCLUSIONS: This report is the first autopsy study to include
      demographic data, etiologic diagnosis, and respective histopathological findings
      in patients with HIV/AIDS and acute respiratory failure. Further studies are
      necessary to elucidate the complete pulmonary physiopathological mechanism
      involved with each HIV/AIDS-associated disease.

PMID- 18719762
TI  - Correlation between lumbar lordosis angle and degree of gynoid lipodystrophy
      (cellulite) in asymptomatic women.
AB  - INTRODUCTION: Gynoid lipodystrophy (cellulite) has been cited as a common
      dermatological alteration. It occurs mainly in adult women and tends to gather
      around the thighs and buttocks. Its presence and severity have been related to
      many factors, including biotype, age, sex, circulatory changes, and, as some
      authors have suggested, mechanical alterations such as lumbar hyperlordosis.
      OBJECTIVE: To correlate the degree of cellulite with the angle of lumbar lordosis
      in asymptomatic women. METHODS: Fifty volunteers were evaluated by digital
      photos, palpation, and thermograph. The degree of cellulite was classified on a
      scale of 1-4. Analyses were performed on the superior, inferior, right and left
      buttocks (SRB, IRB, SLB, ILB), and the superior right and left thighs (SRT, SLT).
      The volunteers underwent a lateral-view X-ray, and the angle of lumbar lordosis
      was measured using Cobb's method (inferior endplate of T12 and the superior
      endplate of S). The data were statistically analyzed using ANOVA and Spearman's
      correlation. A significance level of 5% was adopted. RESULTS: Volunteers had a
      mean age of 26.1+/-4.4 years and a mean body mass index of 20.7+/-1.9 kg/m(2).
      There was no significant difference in lumbar lordosis angle between those with
      cellulite classes 2 and 3 (p>or=0.297). There was also no correlation between
      lumbar lordosis angle and the degree of cellulite (p>or=0.085 and r>or=0.246).
      CONCLUSIONS: The analysis suggests that there is no correlation between the
      degree of cellulite and the angle of lumbar lordosis as measured using Cobb's
      method.

PMID- 18719763
TI  - Acetabular reconstruction with human and bovine freeze-dried bone grafts and a
      reinforcement device.
AB  - BACKGROUND: This is a cohort trial (1997-2005) of 49 patients submitted to an
      acetabular component revision of a total hip arthroplasty, using impacted human
      and bovine freeze-dried cancellous bone grafts (H&FDBG) and a reinforcement
      device. OBJECTIVE: To compare clinical/radiographic graft incorporation
      capability between cancellous bone grafts. PATIENTS/METHODS: There were two
      groups: I (n=26) receiving human grafts and II (n=25) receiving bovine grafts.
      The average follow-up times were 55 and 49 months, respectively. Clinical
      analysis was based on the Merle d'Aubigne and Postel score, and the radiographic
      analysis involved an established score based on Conn's et al. criteria for
      radiographic bone incorporation. RESULTS: No clinical/radiographic differences
      were found between the groups and both showed an overall rate of 88.5% and 76% of
      graft incorporation (p=0.424). CONCLUSION: The results presented here are
      comparable to those in the literature with the use of deep-FG. Therefore,
      cancellous bone grafts can be safely and adequately used in acetabular component
      revision in total hip arthroplasty.

PMID- 18719764
TI  - A practical protocol to measure common carotid artery intima-media thickness.
AB  - OBJECTIVE: To describe and test a practical protocol to measure common carotid
      intima-media thickness that uses the combined values of two longitudinal
      examination angles to increase sensitivity. METHOD: Between February and
      September 2005, 206 patients underwent duplex scan examination of carotid
      vessels, and the intima-media thickness of 407 common carotids were measured in
      three angles: transversal, longitudinal posterolateral, and anterolateral, with
      three intima-media thickness measurements for each near and far wall. In addition
      to numbers obtained from the three angles of measurement, a fourth visual
      perspective was obtained by combining the intima-media thickness results of
      posterolateral and anterolateral longitudinal views and considering the thickest
      wall measurement. RESULTS: Two hundred seventy (66.3%) carotid arteries had an
      intima-media thickness thicker than 1mm. The mean intima-media thickness values
      achieved by the different incidences were 1.26+/-0.6 mm (transversal), 1.17+/
      0.54 mm (longitudinal anterolateral), and 1.18+/-0.58 mm (longitudinal
      posterolateral). A significant difference in intima-media thickness measurement
      values was observed when the three angles of examination plus the combined
      positive results of both longitudinal angles were compared by ANOVA (P=0.005).
      The LSD Post-Hoc test determined that the combined longitudinal view results were
      similar to the transversal views (P=0.28) and had greater intima-media thickness
      means than isolated anterolateral or posterolateral longitudinal views (P=0.02
      and 0.05, respectively). CONCLUSIONS: The protocol presented is a practical
      method for obtaining common carotid artery intima-media thickness measurements.
      The combined longitudinal posterolateral and anterolateral longitudinal views
      provide a more sensitive evaluation of the inner layers of the carotid walls than
      isolated longitudinal views.

PMID- 18719765
TI  - A study of anatomical variability of the omohyoid muscle and its clinical
      relevance.
AB  - OBJECTIVE: The omohyoid muscle is a long, thin muscle consisting of superior and
      inferior bellies and an intermediate tendon, which runs obliquely in the lateral
      cervical region. The omohyoid is important in neck dissections because it is the
      surgical landmark for level III and IV lymph node metastases. METHODS: In the
      present study, the anterior and posterior triangle of the neck was dissected in
      35 male cadavers and observed for variations in the omohyoid bilaterally.
      Observations were focused on variations in number, attachments, and position of
      omohyoid. RESULTS: Among the 35 cadavers studied, double omohyoid was present in
      one cadaver, inferior belly originated from the clavicle in three cadavers,
      superior belly merged with the sternohyoid in two cadavers, and the omohyoid
      received additional slips from the sternum in one cadaver. Standard attachment
      and position of the omohyoid was observed in the remaining cadavers. CONCLUSION:
      Variations of this muscle are important because of its close relation to the
      large vessels and brachial plexus. Because of the direct adhesion of the
      intermediate tendon to the anterior wall of the internal jugular vein and its
      connection with it through a thin lamina of the pretracheal layer of the cervical
      fascia, the contraction of the omohyoid muscle has a direct effect on the lumen
      of this vessel.

PMID- 18719766
TI  - Does gestrinone antagonize the effects of estrogen on endometrial implants upon
      the peritoneum of rats?
AB  - OBJECTIVE: To evaluate the effects of estrogen treatment in combination with
      gestrinone on an experimental rat model of endometriosis. METHODS: Uterine
      transplants were attached to the peritoneum of female Wistar rats via a surgical
      autotransplantation technique. The implanted area was measured during the
      proestrus phase and after hormonal treatment. We performed morphometric analysis
      and examined the macroscopic and morphometric alterations of endometrial implants
      after hormonal treatment in ovariectomized rats. RESULTS: The high dose of
      estrogen caused macroscopic increases in the endometrial implant group compared
      with other groups, which were similar to increases in the proestrus phase. The
      low dose showed morphometric development of implants, such as an increase in
      number of endometrial glands, leukocyte infiltration and mitosis. Gestrinone
      antagonized both doses of estrogen. CONCLUSION: Our findings suggest that
      gestrinone antagonizes estrogen's effects on rat peritoneal endometrial implants.

PMID- 18719768
TI  - Metric measurements and attachment levels of the medial patellofemoral ligament:
      an anatomical study in cadavers.
AB  - OBJECTIVE: To determine the metric measurements and to verify the attachment
      levels of the medial patellofemoral ligament in human cadavers. METHODS:
      Seventeen knees (eight right and nine left knees) from 10 cadavers (nine male and
      one female) were dissected and stored in a 10% formaldehyde solution. All of the
      knees were whole and did not show any macroscopic signs of injuries. RESULTS: The
      medial patellofemoral ligament was present in 88% of the knees studied, localized
      transversally between the medial femoral epicondyle and the medial margin of the
      patella. Its dimensions were quite variable, even between the knees of the same
      individual. The width of the patellar insertion ranged from 16 to 38.8 mm, with a
      mean of 27.90 mm, and its mean length was 55.67 mm. The margins of the ligament
      were concave or rectilinear. At the upper margin, the concave form predominated
      and was better characterized, while at the lower margin, the rectilinear form
      predominated. CONCLUSIONS: The medial patellofemoral ligament is a very distinct
      structure with variable anatomical aspects and is always located in a plane
      inferior to the vastus medialis obliquus muscle.

PMID- 18719769
TI  - A study of the antioxidant effect of alpha lipoic acids on sperm quality.
AB  - OBJECTIVE: Assisted reproductive techniques are useful in helping infertile
      couples achieve successful conception. Initial studies have shown that sperm
      cryopreservation, one step in assisted reproduction, causes a dramatic reduction
      in sperm quality. This has been attributed to, among other things, free radical
      activities. The aim of the present study was to minimize this oxidative attack by
      adding an antioxidant into the sperm microenvironment. Alpha lipoic acids were
      selected for this purpose for their efficient free radical scavenging properties
      and solubility in lipid and aqueous phases. METHODS: For this investigation,
      semen from six Boer bucks was pooled. Seminal analysis of the baseline prior to
      incubation of samples with different concentrations of Alpha lipoic acids
      (0.00625, 0.0125, 0.025, 0.05, 0.1 mmol/ml) was performed, and post-seminal
      analysis was conducted after a one-hour incubation. The comet assay was used to
      observe the effect of Alpha lipoic acids on sperm DNA integrity. Statistical
      analysis using an unpaired t-test with a significance level of p<0.05 was then
      performed. RESULTS: Our results indicate that the sperm motility rate was
      improved after incubation with Alpha lipoic acids at a concentration of 0.02
      mmol/ml. This concentration was also capable of reducing DNA damage. CONCLUSION:
      In conclusion, Alpha lipoic acids renders cryoprotection to sperm, thereby
      improving sperm quality.

PMID- 18719767
TI  - Oxidized low-density-lipoprotein accumulation is associated with liver fibrosis
      in experimental cholestasis.
AB  - OBJECTIVE: The aim of the present study was to examine the probable relationship
      between the accumulation of oxLDL and hepatic fibrogenesis in cholestatic rats.
      INTRODUCTION: There is growing evidence to support the current theories on how
      oxidative stress that results in lipid peroxidation is involved in the
      pathogenesis of cholestatic liver injury and fibrogenesis. One of the major and
      early lipid peroxidation products, OxLDL, is thought to play complex roles in
      various immuno-inflammatory mechanisms. METHODS: A prolonged (21-day)
      experimental bile duct ligation was performed on Wistar-albino rats. Biochemical
      analysis of blood, histopathologic evaluation of liver, measurement of the
      concentration of malondialdehyde (MDA) and superoxide-dismutase (SOD) in liver
      tissue homogenates, and immunofluorescent staining for oxLDL in liver tissue was
      conducted in bile-duct ligated (n=8) and sham-operated rats (n=8). RESULTS:
      Significantly higher levels of MDA and lower concentrations of SOD were detected
      in jaundiced rats than in the sham-operated rats. Positive oxLDL staining was
      also observed in liver tissue sections of jaundiced rats. Histopathological
      examination demonstrated that neither fibrosis nor other indications of
      hepatocellular injury were found in the sham-operated group, while features of
      severe hepatocellular injury, particularly fibrosis, were found in jaundiced
      rats. CONCLUSION: Our results support the finding that either oxLDLs are produced
      as an intermediate agent during exacerbated oxidative stress or they otherwise
      contribute to the various pathomechanisms underlying the process of liver
      fibrosis. Whatever the mechanism, it is clear that an association exists between
      elevated oxLDL levels and hepatocellular injury, particularly with fibrosis.
      Further studies are needed to evaluate the potential effects of oxLDLs on the
      progression of secondary biliary cirrhosis.

PMID- 18719770
TI  - Variations in the extensor muscles of the hand and their clinical implications.

PMID- 18719771
TI  - Furazolidone and serotonin syndrome: is there any association?

PMID- 18719772
TI  - Intravenous cyclophosphamide therapy in adults with Henoch-Schonlein purpura.

PMID- 18719773
TI  - A case of pseudo-hypertrophic cardiomyopathy: a congenital heart disease.

PMID- 18719774
TI  - Missed gallstones in the bile duct and abdominal cavity: a case report.

PMID- 18719775
TI  - Delayed-onset hepatic encephalopathy induced by zolpidem: a case report.

PMID- 18719776
TI  - Isolated noncompacted myocardium in an elderly patient.

PMID- 18719777
TI  - [Life as a common good].

PMID- 18719778
TI  - [Safety of magnetic resonance imaging after coronary angioplasty with stent].

PMID- 18719779
TI  - [Cholecystectomy in a patient with gallstone pancreatitis: immediate surgery or
      late?].

PMID- 18719780
TI  - [What is the best sample size to conduct a clinical trial?].

PMID- 18719781
TI  - [Bladder cancer - treatment of invasive and metastatic carcinoma].

PMID- 18719782
TI  - [Overweight, a new reality on the nutritional status of preschool children in
      Natal (RN): epidemic or moral panic?].

PMID- 18719783
TI  - Beta-Blockers for non-cardiac surgery: a different approach after the poise data
      or await more information?

PMID- 18719785
TI  - [Craniopagus twins vascular dependence].

PMID- 18719786
TI  - [The opinion of women on menopause and treatment of its symptoms].
AB  - OBJECTIVE: To evaluate the perception of a group of women from Belo Horizonte,
      Minas Gerais, Brasil, with respect to menopause and its treatment. METHODS: A
      secondary analysis was performed on data from a population-based, cross sectional
      study carried out with 378 Brazilian born women between 40 and 65 years of age,
      with 11 years or more of formal education. Some women added spontaneous comments
      to the end of the questionnaire on sexuality handed out by research assistants
      and self-responded anonymously. There were those who provided comments at the end
      of the questionnaire and those who did not. The groups were compared with respect
      to sociodemographic and reproductive characteristics using Pearson's chi-square
      test. Comments were transcribed in their entirety to a computerized file for
      thematic content analysis, and units of meaning were identified and classified.
      RESULTS: Approximately one-third of the women (114/378) provided comments.
      Significantly more women with lower income levels provided comments as compared
      to those with higher income levels. The principal identified categories of
      analysis were: a) uncertainty and/or confusion, mainly with regard to anguish,
      stress and doubts about menopause; b) symptoms that lead to negative feelings,
      such as hot flushes, vaginal dryness and mood changes; and c) hormone replacement
      therapy, fears and perception of a lack of conviction in the physicians who
      prescribe it. CONCLUSION: The comments indicate that more attention must be given
      to the problems perceived in climacteric women with a special emphasis on those
      of the lower incomes levels.

PMID- 18719787
TI  - Neuroendocrine tumors: a registry of 1,000 patients.
AB  - Neuroendocrine tumors (NET) can originate diffusely in most organs, with varying
      clinical presentations. The relative rarity of these tumors, previously referred
      to as carcinoids, encouraged several centers worldwide to study NET. Since 2003,
      a similar group was established in , the GETNE - Grupo de Estudo de Tumores
      Neuroendocrinos (Neuroendocrine Tumors Study Group) that included 32 centers,
      from all regions of Brasil. A patient database was initiated, collecting
      information about NET, regardless of the site of origin. OBJECTIVES: The present
      study shows initial results of 1000 patients included. METHODS: Descriptive
      statistical analyses, as well as overall survival rates for different groups of
      NET patients registered by GETNE. RESULTS: Most patients presented with thoracic
      NET (71.6%), while 20.2% had gastro-entero-pancreatic tumors. Median follow-up of
      all patients included was 33.7 months (range 1-141 months). At the time of the
      analysis, 29.3% of the patients were still alive (of these, 45.7% were alive with
      no evidence of disease). CONCLUSION: This is the largest database of NET in, and
      further accrual of new patients, as well as individual study results are expected
      in the near future.

PMID- 18719788
TI  - Dexmedetomidine in anesthesia of children submitted to videolaparoscopic
      appendectomy: a double-blind, randomized and placebo-controlled study.
AB  - OBJECTIVES: To evaluate the hemodynamic responses to nociceptive stimuli in
      children submitted to videolaparoscopic appendectomy under balanced anesthesia
      with isoflurane and dexmedetomidine. METHODS: Randomized, double-blind and
      placebo-controlled study involving 26 children submitted to videolaparoscopic
      appendectomy carried out at Hospital Sao Lucas (PUCRS) between May 2004 and
      February 2005. Patients were assigned to two groups: (a) Dexmedetomidine group
      (n=13): infusion of 1 microg/kg over 10 minutes and maintenance dose of 0.5
      microg/kg/h) as an adjuvant to inhaled isoflurane anesthesia; (b) Control group
      (n=13): normal saline infusion at a similar rate and volume of the
      dexmedetomidine infusion. During the different surgical and anesthetic periods,
      groups were compared regarding heart rate, systolic and diastolic arterial blood
      pressures as well as need of supplemental fentanyl infusion. Student's t test,
      ANOVA, and Finner's procedure were used for statistical analysis. RESULTS: During
      the strongest nociceptive stimuli (airway access and abdominal catheter
      placement), the heart rate and systolic blood pressure increased significantly
      (p<0.001) in the control group compared to the dexmedetomidine group. Compared to
      baseline levels, the hemodynamic responses to nociceptive stimuli were more
      stable when dexmedetomidine was used in combination with inhaled isoflurane
      anesthesia. The need for supplemental doses of fentanyl and the hemodynamic
      parameters were similar for both groups. CONCLUSION: Dexmedetomidine combined
      with inhaled isoflurane for anesthesia of children submitted to videolaparoscopic
      appendectomy, efficiently blocks the hemodynamic responses to nociceptive
      stimuli. When compared to placebo, the use of dexmedetomidine did not change the
      need for supplemental doses of fentanyl for maintenance of hemodynamic parameters
      during the intraoperative period.

PMID- 18719789
TI  - [Factors associated to glycaemic control in patients with type 2 diabetes].
AB  - OBJECTIVE: Evaluate the factors influencing blood glucose control of type 2
      diabetic patients attended at a tertiary health care center. METHODS: A
      retrospective study by review of medical records of patients who attended the
      Diabetes Clinic at the University of Caxias do Sul was carried out. Patients were
      evaluated for glycaemic and metabolic control and divided according to glycated
      hemoglobin at the beginning and end of the period in question, in compensated and
      not compensated. The factors associated with glycaemic control were analyzed.
      RESULTS: Seventy three patients were included in the analysis. On the average,
      improvement of parameters related to glycaemic, pressure and lipid control during
      the average of 20 months of treatment was observed. In the beginning of the
      follow-up period, 25% of patients had glycated hemoglobin < 7%, 22.7% had LDL
      cholesterol < 100mg/dL, 8.7% had systolic blood pressure < 130 mmHg and diastolic
      < 80 mmHg and no patients had all parameters meeting the recommended goals. At
      the last visit the percentages were, 42.3%, 37.5%, 30.2% and 9.6% respectively.
      In the multivariate analysis, younger age, higher levels of LDL cholesterol and
      insulin use were associated with poor blood glucose control. CONCLUSION: A small
      part of the sample simultaneously achieved the goals for blood glucose, lipids
      and blood pressure control. Some factors, such as age and gender can be
      determinants to achieve control of diabetes. Greater efforts are still needed to
      achieve the goals for treatment in type 2 diabetic patients.

PMID- 18719790
TI  - [Nutritional evaluation and cardiovascular risk in executives submitted to a
      check-up].
AB  - OBJECTIVE: To evaluate the nutritional status and cardiovascular risk among
      executives. METHODS: In a cross-sectional study. 329 executives of both genders,
      aged 31 to 70 years, were evaluated during a health check-up in a private
      hospital in the city of Sao Paulo. The variables related to weight, height and
      waist circumference were measured and Body Mass Index - BMI (kg/m(2)) was
      determined. Blood pressure and serum levels of total cholesterol and fractions,
      triacylglycerol, glucose and uric acid were analyzed. Physical activity was
      evaluated by the International Physical Activity Questionnaire (IPAQ) and
      cardiovascular risk was estimated by the Framingham Scoring. The variance
      analysis and the Bonferroni methods were used for statistical treatment. RESULTS:
      The mean age was 44.6 (SD=6.8), with the male gender predominating (89.7%). As
      for lifestyle, 17% were tobacco smokers and 7.3% sedentary. The mean values found
      in the clinical and biochemical exams were the following: blood pressure of 117 x
      78.6 mmHg (SD=12 x 8.3), total cholesterol of 200.5 mg/dL (SD=35.9), LDL-c of
      121.8 mg/dL (SD=29.9), HDL-c of 52.2 mg/dL (SD= 10.9), triacylglycerol of 133.7
      mg/dL (SD=76.8), glucose of 96.3 mg/dL (SD=20.5) and uric acid 4.2 and 6.0 mg/dL
      (SD=1.0 and 0.9) for men and women respectively. The BMI mean for all executives
      was classified as overweight (26.1 kg/m(2); SD=6.8). Waist circumference was
      normal in women (79.6 cm; SD=7.3) and indicated a high risk level of chronic
      disease for the men (96.1cm; SD=8.9). The average Framingham Risk was 5.7%.
      CONCLUSION: The executives were overweight and presented low cardiovascular risk,
      according to the Framingham Scoring.

PMID- 18719791
TI  - [The influence of programmed physical activity on blood pressure of hypertensive
      elderly patients on non-pharmacological treatment].
AB  - OBJECTIVE: Assess the influence of physical activity on the blood pressure of
      hypertensive elderly patients on non-pharmacological treatment (NPT). METHODS:
      The authors studied men and women, over 60 years, with stage I hypertension who
      were not using antihypertensive medication. These patients had been randomly
      allocated to one of two groups: Control Group (CG) - oriented to NPT; and Study
      Group (SG) - NPT and a program that included supervised physical activity
      consisting of 1-hour sessions, 3 times a week. Duration of the study was 6
      months. Screening and follow-up tests every 3 months, at Visits 1, 2 and 3
      included a clinical evaluation, ECG, a treadmill stress test, Ambulatory Blood
      Pressure Measurement (ABPM) and an Echocardiogram. The authors used the Friedman
      test for the evolutionary analysis of the intra-groups means and Student's t test
      to compare independent data between groups. RESULTS: Twenty-four patients were
      randomized in the SG (5 men) and 21 in the CG (4 men). The 6-month follow-up
      period was completed by 22 patients in the SG and 13 in the CG. Blood pressures
      found by the ABPM in V1, V2 and V3 were 134.2 +/-14.5, 136.1 +/-9 and 143.7+/
      13.9 mmHg for Systolic Blood Pressure in the CG; and 135.6 +/-11.4, 138.7 +/-12.2
      and 133.9 +/-8.5 mmHg in the SG. For Diastolic Blood Pressure, values in the CG
      were 78.7+/-5.8, 82.3+/-6.2 and 83.3 +/-9.2 mmHg; and in the SG, 80.1 +/-6.8,
      81+/-6.6 and 80.8 +/-7.3 mmHg. CONCLUSION: Programmed and supervised physical
      activity was more efficient for maintaining adequate blood pressure control in
      these elderly with stage I hypertension in the study group, when compared to the
      control group.

PMID- 18719792
TI  - [Risk of overweight in adolescents from different socioeconomic levels].
AB  - BACKGROUND: To analyze the association between risk factors and presence of
      overweight in adolescents from different socioeconomic levels. METHODS: A cross
      section analysis with 888 youths recruited from both genders with ages ranging
      from 11 to 17 years was carried out. The body mass index was calculated through
      body mass and height values, and was used as the overweight indicator. Physical
      activity, food intake, and socioeconomic levels (high and low) were obtained by
      questionnaires. Data were analyzed by chi-square test and binary logistic
      regression. RESULTS: For adolescents in the lower socioeconomic level, both
      inadequate food intake (Odds Ratio [OR]= 4.59) and parent overweight (OR= 5.33)
      were associated to overweight. Among adolescents in the higher socioeconomic
      level, maternal education (OR= 0.57), study in private school (OR= 3.04), and
      parent overweight (OR= 3.47) were associated to development of overweight.
      CONCLUSION: In both socioeconomic levels, parent overweight was an important risk
      factor associated with overweight. The other risk factors were different among
      the socioeconomic levels.

PMID- 18719793
TI  - [Non-metastatic breast cancer specific-survival of patients after treatment with
      adjuvant chemotherapy].
AB  - OBJECTIVE: Analyze the 5-year breast cancer specific-survival rate of women
      diagnosed with invasive non-metastatic disease, who as part of their primary
      treatment underwent surgery followed by adjuvant chemotherapy. METHODS: Four
      hundred twenty eight patients diagnosed between 1998 and 2000 were recruited from
      all oncology services of the municipality of Juiz de Fora, MG, Brasil. Survival
      time was counted from the date of the histopathological diagnosis and the date of
      death due to breast cancer was considered the adverse event. Women alive until
      December 2005, the final date of the follow-up, were censored. For those who
      interrupt treatment, censor date was the last follow-up in the medical records.
      Kaplan-Meier survival curves were estimated, with the differences assessed by the
      log-rank test. RESULTS: Mean age was 51.2 years, and most (72.6%) were Caucasian.
      Clinical Stages II (47.4%) and III (38.6%) predominated. Breast cancer specific
      five-year survival rate was 82.0%. A worst survival was observed among women with
      disease diagnostic before menopause (p=0.02), with tumor size greater than 2.0 cm
      (p=0.05), with lymph node involvement (p=0,000), in a more advanced disease stage
      (p=0.000), on a full adjuvant chemotherapy regimen (p=0.03), and who used hormone
      therapy (p=0.05). CONCLUSION: This research allowed identification of the profile
      and disease survival of breast cancer patients who used adjuvant chemotherapy.
      These results stimulated the adoption of intensive strategies by the local health
      authorities for disease control and prevention in this population, emphasizing
      the increasing need of breast cancer screening, mainly for women considered as of
      high risk and the availability of timely treatment for all cases diagnosed.

PMID- 18719794
TI  - [Functional limitation and survival of community dwelling elderly].
AB  - OBJECTIVE: The present study aims to analyze the functional limitation as risk
      factor of death of elderly dwelling in a community and its relationship with
      socio-demographic, physical health and neuropsychiatric related factors. METHODS:
      A prospective study was carried out in the city of Santa Cruz, Rio Grande do
      Norte, Brasil. A total of 310 randomly selected elderly formed the baseline
      (63.5% women, 73.7+/-9.03 years). The Katz Index was used to evaluate the
      functional capacity for basic activities of daily living. The follow-up period
      was of 53 months. The statistical methods used were bivariate analysis (Pearson's
      chi-square), survival analysis by the Kaplan-Meyer method, followed by Cox
      regression in multivariate analysis, with the respective hazards ratios (HR).
      RESULTS: A total of 60 elderly (20.5%) died during the study follow-up; the main
      cause of death was cardiovascular disease. The mean survival time was of about
      24.8 months, and the main risk factors identified at Cox regression were
      cognitive deficit (HR= 4.30) and stroke (HR= 3.49) besides the dependence for the
      basic activities of daily living (HR = 3.17). CONCLUSION: The functional
      limitation was an independent risk factor for death.

PMID- 18719795
TI  - [Beer-Fick criteria and generic drugs in Brazil].
AB  - BACKGROUND: Determine, according to the Beer-Fick criteria, the prevalence of
      drugs potentially inappropriate for the elderly available as generic medication
      in Brazil. METHODS: Analysis of the list of generic medications issued by "
      Diario Oficial da Uniao" on July/12/2004 and of the page of the National Agency
      for Sanitary Surveillance (ANVISA) - www.anvisa.gov.br, using the Beers-Fick
      criteria. RESULTS: From the list of 299 products 20 (6.7% of the total) included
      in the Beers-Fick criteria were analyzed, mainly in the categories of
      anxiolytics, platelet antiaggregants, antiallergics, anti-angina and
      vasodilators, antiarrythmics, antidepressants, antispasmodics, anti
      hypertensive's, non steroid antinflammatories, antiulceratives and cardiac
      glycosides. These criteria do not include drugs such as cough suppressants,
      cinnarizine, diltiazem, piracetam, quinolones, xanthines, creams, ointments and
      ophthalmic solutions which are also present in the list of generic medication.
      CONCLUSION: The Beers-Fick criteria may prevent use of drugs potentially
      inappropriate for the elderly, however, it should be stressed that these criteria
      are not complete for Brazilian generic medications.

PMID- 18719796
TI  - [Adverse effects of hypolipemic drugs: how to treat in clinical practice].
AB  - Hypolipemic drugs improve coronary morbidity and mortality and appear to be safe;
      nevertheless appropriate monitoring is recommended. Adverse effects are reported
      that are frequently transitory. Severe adverse effects are infrequent, but
      clinicians must correctly screen them; symptoms and laboratory changes must be
      carefully interpreted. Often they call for special treatment and replacement of
      the hypolipemic drugs in use. This article emphasizes how to treat dyslipidemia
      if skeletal muscle and liver involvement are present. Briefly other adverse
      effects are also reported.

PMID- 18719797
TI  - [About correlation between bioethics and medical psychology].
AB  - The authors make a study about the correlation between bioethics and medical
      psychology. They divide the study in two parts. The first part they discuss the
      philosophical concepts about the distinction between morals and ethics, they deal
      with ethics applied to medicine and they are trying to define what is meant by
      subject and describe its three basic principles: autonomy, beneficence, non
      maleficence and justice. Consequently in this part they trace route that started
      from ethics in its philosophical origins and moved on to ethics in its
      application to medicine. The second part is dedicated to the definition of the
      field of study of medical psychology, they study some aspects of the emotional
      relation of the patient with his illness, the relation of the doctors of his
      medicine and the relationship between doctor and his patient. They discussed some
      clinical issues where they observe this correlation. At last, they try to draw
      some conclusions.

PMID- 18719798
TI  - [Raising HDL cholesterol: which is the best strategy?].
AB  - After having reached the objective for the LDL cholesterol levels, it becomes
      imperative to reach the objective for HDL cholesterol, known for its anti
      atherogenic properties, generally confirmed in many epidemiological studies. This
      review deals, in a clear and concise manner, with the different alternatives
      available in daily clinical practice to raise the HDL cholesterol levels of
      patients, to achieve better outcomes in terms of morbidity and mortality in
      cardiovascular disease.

PMID- 18719799
TI  - Epidemiological and molecular characteristics of HIV-1 infection among female
      commercial sex workers, men who have sex with men and people living with AIDS in
      Paraguay.
AB  - An HIV seroprevalence and molecular study was conducted among 935 subjects: 723
      female commercial sex workers, 92 men who have sex with men and 120 HIV-positive
      volunteers. The reported injection drug use rates were 0.7% in female commercial
      sex workers and 3% in men who have sex with men. Sexually transmitted infections
      were reported in 265 (37%) of the female commercial sex workers and 38 (41%) of
      the men who have sex with men. A total of 20 (2.8%) female commercial sex workers
      and 12 (13%) men who have sex with men became HIV infected during the study
      period. A history of sexually transmitted infection increased the risk of
      subsequent HIV infection twofold (adjusted odds ratio of 2.5) among the female
      commercial sex workers, while cocaine use had an adjusted odds ratios of 6.61
      among men who have sex with men. From 130 samples, and based on heteroduplex
      mobility assaying for the env gene, with sequencing of part of pol and/or full
      genomes, subtype B was the predominant subtype identified (66%); followed by
      subtype F (22%) and subtype C (4%). Recombinant CRF12-BF strains were identified
      in 6% and CRF17_BF was identified in 2%.

PMID- 18719800
TI  - Malaria outbreaks in a non-endemic area of Brazil, 2005.
AB  - In March 2005, a resident of the municipality of Monte Alegre de Minas, State of
      Minas Gerais, without any history of traveling to endemic areas for malaria, was
      diagnosed with Plasmodium vivax infection and local mosquito-borne transmission
      was suspected. The epidemiological investigation identified another 10 cases with
      local transmission and all of them were related to the imported malaria case that
      was detected in this region. The potential exposure site was the banks of the
      river Tejuco, an area frequented by mineral prospectors. Some of these
      prospectors were known to have come from states with malaria transmission. In the
      autochthonous cases, Plasmodium vivax and Plasmodium falciparum were diagnosed.
      Entomological investigation identified Anopheles (Nyssorhynchus) darlingi,
      Anopheles (Nyssorhynchus) albitarsis, Anopheles (Nyssorhynchus) triannulatus and
      Anopheles (Nyssorhynchus) parvus. After the first outbreak, another three
      autochthonous cases were notified in municipality of Monte Alegre de Minas, in
      the same year. The occurrence of these outbreaks highlights the importance of
      surveillance systems in areas that are nonendemic for malaria.

PMID- 18719801
TI  - [High prevalence of genotype 1 in individuals with hepatitis C in Belo Horizonte,
      MG].
AB  - The hepatitis C virus is characterized by significant genetic heterogeneity. It
      is currently classified into six main genotypes and several subtypes. Determining
      the genotype of the virus is important in clinical practice for guiding the
      treatment for individuals with chronic hepatitis C. The prevalence of different
      genotypes and subtypes of the hepatitis C virus has not been fully studied in
      some regions of Brazil. In this study, 788 samples from patients with chronic
      hepatitis C who were attended at the Viral Hepatitis Reference Centers in Belo
      Horizonte were analyzed between 2002 and 2006. The genotyping of the virus was
      performed by direct sequencing of the 5 UTR region. Additionally, phylogenetic
      analysis was performed, including all of the genotypic variants obtained. High
      prevalence of genotype 1 (78.4%; 1b [40.4%], 1a [37.5%] and 1a/b [0.5%]) was
      observed, followed by genotypes 3a (17.9%) and 2b (3.1%). Three samples were
      identified as genotype 2a/c (0.4%) and two as genotype 4 (0.2%). The phylogenetic
      analysis showed the expected segregation of the sequences obtained, with regard
      to the reference sequences for genotypes 1, 2, 3 and 4, except for two samples of
      genotype 1a. The high prevalence of genotype 1 (78.4%) found in this population
      from Belo Horizonte was similar to previous reports from other cities such as Rio
      de Janeiro, but it was higher than what has been described in Sao Paulo and in
      the south of the country. The presence of rare atypical sequences from the 5 UTR
      region suggests that variants in the hepatitis C virus exist in this population.

PMID- 18719802
TI  - [Incidence of tuberculosis among indigenous people in the municipality of Sao
      Gabriel Cachoeira, AM].
AB  - Starting in 1999, the Ministry of Health implemented its Tuberculosis Control
      Program in the municipality of Sao Gabriel da Cachoeira, State of Amazonas. With
      the aim of investigating whether this strategy had promoted changes in
      tuberculosis incidence among indigenous people in that area, the medical records
      of 768 patients were studied retrospectively, divided in two groups. Group I
      consisted of cases treated between 1994 and 1998 and Group II consisted of cases
      treated between 1999 and 2003. The mean annual incidence rates were,
      respectively, 239 and 284 cases of all tuberculosis forms per 100,000
      inhabitants. The pulmonary form predominated, accounting for 88.2% and 85.9% of
      the cases, and the cure rate was high (97.2% and 91.5%), respectively in Groups I
      and II. There was no impact with regard to reducing the incidence rate of this
      disease, thus showing that a high risk of contracting tuberculosis persists among
      indigenous people in that area.

PMID- 18719803
TI  - [Causes of death among patients with acquired immunodeficiency syndrome autopsied
      at the Tropical Medicine Foundation of Amazonas].
AB  - The aim of this study was to investigate the causes of death among 129 AIDS
      patients that were autopsied at the Tropical Medicine Foundation of Amazonas
      between 1996 and 2003. The degree of concordance between the autopsy diagnoses
      and the clinical diagnoses was observed. The disease that most frequently caused
      death was tuberculosis (28%), followed by bacterial pneumonia (17%),
      histoplasmosis (13%), toxoplasmosis (10%), pneumocystosis (8%), cryptococcosis
      (5%), bacterial sepsis (4%) and other causes (15%). The concordance between the
      clinical diagnosis before death and the autopsy was 51.9%. The main organ
      involved was the lungs (82.2%). The length of survival from the time of the
      laboratory diagnosis to death ranged from one month to 120 months. The mean
      length of survival was 15 days and 56% died less than one month after the
      diagnosis, while 15 patients died on the same day that they were diagnosed. These
      results show the importance of autopsies in elucidating the causes of death among
      AIDS patients.

PMID- 18719804
TI  - [Temporary and permanent breeding sites for Biomphalaria in Jaboatao dos
      Guararapes, PE].
AB  - A malacological survey of permanent and temporary breeding sites was conducted in
      the Piedade neighborhood of Jaboatao dos Guararapes, Pernambuco, between November
      2006 and November 2007, with the aim of determining the malacological fauna at
      this locality, along with the potential for Schistosomiasis mansoni transmission.
      In addition to Biomphalaria glabrata (Say, 1818), the molluscs Drepanotrema cimex
      (Moricand, 1837), Pomacea sp and Melanoides tuberculatus (Muller, 1774) were
      collected. Among the specimens of Biomphalaria glabrata that were collected,
      1,490 were found alive, and 74 (5%) were positive for Schistosoma mansoni. The
      largest numbers of molluscs collected, and all of the specimens that were
      positive for Schistosoma mansoni, were collected during the annual rainy season.
      The presence of larvae of other trematodes infecting the Biomphalaria glabrata
      molluscs was also observed. These trematodes were from the families Strigeidae
      and Diplostomatidae and, at first sight, they presented morphology that could
      lead to confusion with Schistosoma mansoni cercariae. Thus, knowledge of these
      trematodes becomes essential for the differential diagnosis of the etiological
      agent for schistosomiasis.

PMID- 18719805
TI  - [Prevalence of triatomines (Hemiptera: Reduviidae: Triatominae) infected by
      Trypanosoma cruzi: seasonality and distribution in the Cienega region of the
      State of Jalisco, Mexico].
AB  - The physical and geographical characteristics of the Cienega region, Jalisco,
      Mexico make it suitable for transmission of Trypanosoma cruzi, the causative
      agent for Chagas disease. This study characterizes the prevalence of triatomines
      infected by this parasite, their seasonality and their distribution in this
      region. A total of 328 triatomines were evaluated between January 2005 and June
      2007, from 13 municipalities in the region. April, May and June were the months
      with the highest capture levels. Among the triatomines examined, 57.3% were
      positive for Trypanosoma cruzi, corresponding to 15.4% in urban areas and 84.6%
      in rural areas. The species with greatest prevalence was Triatoma longipennis and
      the species with the highest parasitism rate was Triatoma barberi, with an
      infection rate of 83.3%, whereas the rate for Triatoma longipennis was 67.5%
      (p<0.05). This natural infection in the captured vectors may indicate that
      individuals in this region have high exposure to Trypanosoma cruzi. The recent
      findings of positive Triatoma dimidiata in this region suggest that new species
      are becoming adapted to the ecological conditions of these populations.

PMID- 18719806
TI  - [Evolution of the prevalence of intestinal parasitosis among schoolchildren in
      Caxias do Sul, RS].
AB  - Reports on the prevalence of intestinal parasitosis in Brazil have been local in
      nature, with descriptions of different populations, which makes comprehensive
      diagnosis difficult. With the aim of studying the variation in the prevalence of
      intestinal parasitosis among schoolchildren in Caxias do Sul, Rio Grande do Sul,
      over a 35-year period, 9,787 parasitological stool tests that had been performed
      using centrifugal sedimentation were evaluated. There were positive results from
      5,655 samples (58%), and the most prevalent infestations were of Ascaris
      lumbricoides (47%), Trichuris trichiura (36%), Enterobius vermicularis (8%) and
      the protozoa Giardia lamblia (24%) and Entamoeba coli (20%). The overall
      prevalence diminished from 89% to 37%, indicating an average decrease of 1.4% per
      year. Reductions in prevalence were observed for Ascaris lumbricoides (61 to 26%)
      and Trichuris trichiura (38 to 18%). No significant change was observed for
      Giardia lamblia. The prevalence of Entamoeba coli increased from 29 to 46%. The
      decreases in helminth prevalence were probably due to infrastructure improvements
      and educational actions undertaken in schools.

PMID- 18719807
TI  - [Evaluation of sandfly control measures].
AB  - Collections of sandflies were made between May 2005 and April 2006. The results
      were compared with those from collections undertaken between April 2001 and
      September 2002, in order to evaluate the measures used to decrease the density of
      these insects in Recanto Marista, municipality of Doutor Camargo, State of
      Parana. The collections were carried out by Falcao traps inside domiciles and hen
      sheds, from 10 p.m. to 2 a.m. once a week, four times a month. In 2005 and 2006,
      213,195 sandflies were collected (average of 1,113.8 per hour), compared with
      199,821 (average of 1,653.5 per hour) in 2001 and 2002. Nyssomyia neivai
      predominated (75.4%) in all the ecotopes. Nyssomyia neivai, Nyssomyia whitmani,
      Migonemyia migonei and Pintomyia fischeri accounted for 99.7% of all the
      sandflies collected. The ecotope of hencoops accounted for 88.7% of the sandflies
      collected. It was observed that the sandfly density had decreased between the
      2001-2002 and 2005-2006 collections, especially in homes.

PMID- 18719808
TI  - [Antimicrobial resistance of uropathogens among outpatients, 2000-2004].
AB  - A retrospective study based on the electronic database of a university hospital
      was carried out to investigate the prevalence of etiological agents and their
      susceptibilities to antibiotics, among adult outpatients (> 18 years old) with
      urinary tract infections. Nine hundred and fifty-seven positive urine cultures
      were identified between January 2000 and December 2004. Escherichia coli, Proteus
      mirabilis and Klebsiella sp were the three principal bacterial etiological
      agents. Trimethoprim-sulfamethoxazole presented the highest prevalence of
      bacterial resistance (46.9%), followed by cefalotin (46.7%), nalidixic acid
      (27.6%) and nitrofurantoin (22.3%). Over the study period, nalidixic acid
      presented annual increases of 5.9% in the rate of bacterial resistance (p =
      0.02). Ciprofloxacin also showed an increasing trend, of 3.3% per year (p =
      0.07). This study demonstrated that the antibiotics that are widely recommended
      for empirical treatment of urinary tract infection in adults presented high rates
      of bacterial resistance among the population studied.

PMID- 18719809
TI  - [Hematological, hemostatic and biochemical alterations induced by clofazimine and
      clarithromycin, in single and multiple doses, in rats].
AB  - Clarithromycin and clofazimine have been used to treat leprosy, tuberculosis and
      infections caused by the Mycobacterium avium complex. Since there is a scarcity
      of data on the toxicity of therapeutic regimens that include these drugs, this
      study had the aim of determining the adverse effects of these therapies, through
      evaluation of hematological, hemostatic and biochemical parameters. The drugs
      were administered to male Wistar rats, as monotherapy, in regimens of single and
      multiple doses. Clarithromycin caused increases in the numbers of mononuclear and
      polymorphonuclear leukocytes. Both of the drugs inverted the proportions between
      mononuclear and polymorphonuclear cells and increased the numbers of
      polymorphonuclear cells and degenerating cells. Clofazimine and clarithromycin
      prolonged the prothrombin time and clarithromycin also prolonged the activated
      partial thromboplastin time. Clarithromycin caused increases in total and direct
      bilirubin. Both of the drugs increased the plasma levels of gamma
      glutamyltransferase. Therefore, clofazimine and clarithromycin induce
      hematological, hemostatic and hepatic changes.

PMID- 18719810
TI  - Adult T-cell leukemia/lymphoma: report of two cases.
AB  - Adult T-cell leukemia/lymphoma is a lymphoproliferative disorder of mature T
      lymphocytes associated with infection with human T-cell lymphotrophic virus type
      I (HTLV-I). Adult T-cell leukemia/lymphoma is characterized by clinical and
      laboratory polymorphism that allows it to be classified into four distinct
      subgroups: smoldering, chronic, acute and lymphomatous types. We present here two
      cases of adult T-cell leukemia/lymphoma, respectively in the acute and
      lymphomatous forms of the disease. Case 1 was a 35-year-old woman who presented
      abdominal distension accompanied by hepatosplenomegaly, adenomegaly, skin
      lesions, positivity for anti-HTLV-I antibodies and leukocytosis with the presence
      of flower cells. Case 2 was a 38-year-old man who was admitted with generalized
      lymphadenomegaly, positivity for anti-HTLV-I antibodies, hypercalcemia and
      osteolytic lesions. In this paper, we correlate the clinical-laboratory findings
      of these two cases with data in the literature.

PMID- 18719811
TI  - Acquired non-Chagas megacolon associated with the use of psychiatric medication:
      case report and differential diagnosis with Chagas megacolon.
AB  - A case of acquired megacolon in a 62-year-old man with acute abdomen due to
      sigmoid volvulus is reported. The case was associated with the use of psychiatric
      medications. The aim in this report was to emphasize the differential diagnosis
      with Chagas megacolon. Anatomopathological examination did not show any evidence
      of denervation, ganglionitis and/or myositis, and the serological test for Chagas
      disease was negative.

PMID- 18719812
TI  - Acute Chagas disease outbreak associated with oral transmission.
AB  - Seven individuals living in a town in the Southwest of Bahia developed sudden
      signs of cardiac and systemic impairment, with lethality of 28.6%. Serological
      tests were positive at least in one test in the five patients examined. Forty
      percent of the Triatoma sordida mynphs found inside or around Trypanosoma cruzi
      were found by blood culturig in there out five cases the homes of these cases
      were positive for Trypanosoma cruzi. Transmission probably occurred through
      consumption of water contaminated with triatomine feces. These findings emphasize
      the necessity to evaluation the importance of vectors like Triatoma sordida in
      maintaining the endemicity of this disease.

PMID- 18719813
TI  - Diphyllobothrium latum infection in a non-endemic country: case report.
AB  - Diphyllobothriasis, which is rarely described in Brazil, was reported initially
      as a travelers disease and as an accidental infection in individuals who ate raw
      freshwater fish. This report aims to present the case of a 20-year-old patient
      with confirmed Diphyllobothrium latum infection.

PMID- 18719814
TI  - [First finding of Lutzomyia longipalpis (Lutz & Neiva, 1912) in the urban area of
      Uberlandia, MG, concomitant with the first reported autochthonous case of human
      visceral leishmaniasis].
AB  - The first occurrence of the vector for visceral leishmaniasis, Lutzomyia
      longipalpis, in the urban area of Uberlandia, State of Minas Gerais, and the
      first autochthonous case of human visceral leishmaniasis recorded in the same
      locality are reported. These were notified to the Zoonosis Control Center,
      through the Epidemiological Surveillance sector of the Municipal Health
      Department. The importance of these findings regarding transmission of the
      disease in this area is discussed.

PMID- 18719815
TI  - [Occurrence of multiresistant strains of Pseudomonas aeruginosa producing metallo
      beta-lactamase blaSPM-1 in clinical samples].
AB  - This study analyzed the occurrence of metallo-beta-lactamase genes in clinical
      samples of Pseudomonas aeruginosa from the Hospital Sao Vicente de Paulo, RS. The
      genes were analysed by PCR and the susceptibility profiles were studied by
      diffusion-disk. Forty six strains were analyzed and five strains were positive
      for blaSPM-1 gene.

PMID- 18719816
TI  - [Population dynamics of Aedes aegypti (L) in an urban area with high incidence of
      dengue].
AB  - Aspects of the population dynamics of Aedes aegypti were investigated from
      collections over a two-year period in the urban area of Uberlandia, State of
      Minas Gerais. The population dynamics of this mosquito were influenced by
      physical factors such as temperature and rainfall. High larval densities also had
      an influence on mosquito development.

PMID- 18719817
TI  - [Anopheles (Nyssorhynchus) argyritarsis larvae found in artificial breeding sites
      in the State of Mato Grosso].
AB  - The finding of immature forms of culicid mosquitoes in water tanks at ground
      level is reported. Anopheles argyritarsis and Aedes albopictus were found in the
      municipality of Varzea Grande (MT). It is considered that these artificial
      containers may constitute additional locations that anophelines can use as
      breeding sites.

PMID- 18719818
TI  - International meeting: new diagnostic tests are urgently needed to treat patients
      with Chagas disease.
AB  - Trypanosoma cruzi infection is often not detected early on or actively diagnosed,
      partly because most infected individuals are either asymptomatic or
      oligosymptomatic. Moreover, in most places, neither blood banks nor healthcare
      units offer diagnostic confirmation or treatment access. By the time patients
      present clinical manifestations of advanced chronic Chagas disease, specific
      treatment with current drugs usually has limited effectiveness. Better-quality
      serological assays are urgently needed, especially rapid diagnostic tests for
      diagnosis patients in both acute and chronic phases, as well as for confirming
      that a parasitological cure has been achieved. Some new antigen combinations look
      promising and it is important to assess which ones are potentially the best,
      together with their requirements in terms of investigation and development. In
      August 2007, a group of specialized researchers and healthcare professionals met
      to discuss the state of Chagas infection diagnosis and to build a consensus for a
      plan of action to develop efficient, affordable, accessible and easy-to-use
      diagnostic tests for Chagas disease. This technical report presents the
      conclusions from that meeting.

PMID- 18719819
TI  - Gamna-Gandy bodies in hepatosplenic schistosomiasis mansoni.

PMID- 18719821
TI  - [Histomorphometric differences between the left and right internal thoracic
      arteries in humans].
AB  - OBJECTIVE: The use of the left internal thoracic artery in coronary artery bypass
      surgery is currently recognized as the best option, providing lesser incidence of
      cardiovascular events and superior long-term survival. As a result, great
      expansion of bilateral internal thoracic artery (ITAs) grafts has been observed,
      with additional demonstration of improved long-term survival. Therefore the aim
      of this study was to examine and compare the histomorphometric structure among
      different segments of the left and right ITA. METHOD: Specimens of ITAs harvested
      from 18 cadavers were divided in nine proportional segments. Cuts of each segment
      had been stained with hematoxylin-eosin and Verhoeff-Van Gieson technique. The
      following parameters had been analyzed: perimeter of the arterial lumen,
      thickness of the intima, thickness of the media layer and amount of elastic fiber
      in the media layer. RESULTS: The perimeter of both ATIs decreases downstream its
      course, the proximal segments of the right ITA exhibit perimeter significantly
      greater than left ITA The analysis of the intima thickness revealed no
      significant difference between left and right ITA, except in the segment 9. The
      thickness of media layer showed no statistical difference between them, except in
      the segment 1. The number of elastic layers in the distal left ITA segments is
      significantly higher than right ITA. CONCLUSION: Data analyses from this study
      suggest structural differences between the left and right internal thoracic
      arteries.

PMID- 18719822
TI  - [Cardiac transplantation with bicaval anastomosis and prophylactic graft
      tricuspid annuloplasty].
AB  - OBJECTIVE: This study aims to evaluate the effects of prophylactic heart donor
      tricuspid annuloplasty in patients after heart transplantation with bicaval
      anastomosis. METHODS: From 2002 to 2005, 20 patients undergoing heart
      transplantation with bicaval anastomosis and with a survival rate over 6 months
      were deliberately selected. Patients were divided into two groups: Group I - 10
      patients who underwent prophylactic heart donor tricuspid annuloplasty by the De
      Vega technique; and Group II - 10 patients did not undergo annuloplasty. In both
      groups, presurgical clinical characteristics were the same. The tricuspid
      regurgitation degree was evaluated by transthoracic Doppler echocardiography and
      it was qualified from 0 to 3 (0=absent, 1=mild, 2=moderated, 3=severe).
      Myocardial performance was evaluated by ventricular ejection fraction and
      invasive hemodynamic study performed during routine endomyocardial biopsies.
      RESULTS: Mean clinical follow-up was 14.6+/-4.3 (6 and 16) months. There was only
      one death in group II. It was not related to annuloplasty. Mean degree of
      tricuspid regurgitation in Group I was 0.4+/-0.6 and in Group II was 1.6+/-0.8 (p
      < 0.05). There was a statistically significant difference between both groups in
      right atrium pressure, which was higher in Group II. CONCLUSIONS: In view of the
      limitations of the study, the prophylactic tricuspid annuloplasty in heart donor
      reduced the degree of valvar regurgitation in the medium term after heart
      transplantation with bicaval anastomosis, in spite of not interfering with the
      allograft hemodynamic performance in the period under consideration.

PMID- 18719823
TI  - [Development of isolated swine "working heart model" with parabiotic
      circulation].
AB  - OBJECTIVE: To develop an isolated working heart model with parabiotic circulation
      in swine and verify its stability and possibility to allow effective measurements
      of hemodynamic and metabolic data. METHODS: This model was developed during study
      of association of agents to cardiology. There were performed 18 experiments, each
      with a support animal and a donor animal. Donor animal heart was perfused as
      isolated working heart with parabiotic circulation from support animal. Isolated
      heart underwent regional ischemia by interventricular artery clamping, followed
      by global ischemia. During reperfusion in working heart state mode at 30, 60 and
      90 minutes, contractility indices such as elastance, preload recruitable stroke
      work index and metabolic data were acquired. RESULTS: Support animals were kept
      stable throughout the procedures without use of blood transfusions or vasoactive
      drugs. pH, oxygen partial pressure and hematocrit were kept stable and within
      physiologic ranges. Isolated heart was perfused adequately throughout the
      experiment. All hemodynamic and metabolic data proposed were adequately measured
      in working heart state mode. CONCLUSION: This swine isolated "working heart"
      model was kept stable throughout the experiments with no administration of
      vasoactive drugs and it allowed adequate measurements of metabolic and
      hemodynamic data.

PMID- 18719824
TI  - Early outcome after off-pump coronary artery bypass grafting: effect on mortality
      and stroke.
AB  - OBJECTIVE: One of the major and devastating complications of the coronary artery
      bypass grafting (CABG) is the stroke. Avoiding cardiopulmonary bypass (CPB) may
      reduce this neurological complication. In the past years there was an increased
      interest in the off-pump coronary artery grafting (OPCAB). The benefit of this
      method of revascularization in term of stroke and mortality is controversially
      discussed. METHODS: A retrospective analysis of collected data from 252 patients
      were operated without cardiopulmonary bypass out of 1516 CABG procedures from
      January 2004 through May 2006. The mean age of the patient population was 70+/-11
      years, within a range of 27-88 years. Forty-eight (19%) patients were older than
      80 years and there were 172 (69%) males. Mean graft per patient was 1.78+/-0.79.
      The internal mammary artery (IMA) graft was used in 95% of the patients. For
      eight (3.17%) patients this was the second procedure. RESULTS: Hospital mortality
      was 3.17%; Mean EuroSCORE in these patients was 10.36+/-6.67. No neurological
      complications occurred, six (2.38%) patients had temporary psycho syndrome.
      Postoperative myocardial infarction occurred in three (1.19%) patients. Two
      patients required rethoracotomy as a result of bleeding. Thirty-eight (15%)
      patients needed postoperative therapy for atrial fibrillation. CONCLUSION: CABG
      with OPCAB technique has the benefit of low mortality and morbidity in terms of
      stroke. The advantages of this technique depends on the patient's general
      condition at the time of the operation, the sufficiency of pump function and
      coronary morphology, as well as on the surgeon's experience.

PMID- 18719825
TI  - [Blood mesenchymal stem cell culture from the umbilical cord with and without
      Ficoll-Paque density gradient method].
AB  - OBJECTIVES: Implantation of cell separation and mesenchymal stem cell culture
      techniques from human umbilical cord blood with and without using the Ficoll
      Paque gradient density method (d=1.077 g/ml). METHODS: Ten samples of the
      umbilical cord blood obtained from full-term deliveries were submitted to two
      different procedures of mesenchymal stem cell culture: a) Method without the
      Ficoll-Paque density gradient, which concentrates all nucleated cells; b) Method
      with the Ficoll-Paque density gradient, which selects only low-density
      mononuclear cells. Cells were initially plated into 25 cm(2) cultures flasks at a
      density of 1 x 10(7) nucleated cells/cm(2) and 1 x 10(6) mononuclear cells/cm(2).
      RESULTS: It was obtained 2-13 x 10(7) (median = 2.35 x 10(7)) nucleated
      cells/cm(2) by the method without the Ficoll-Paque gradient density, and 3.7-15.7
      x 10(6) (median = 7.2 x 10(6)) mononuclear cells/cm(2) by the method with the
      Ficoll-Paque gradient density. In all cultures adherent cells were observed 24
      hours after being cultured. Cells presented fibroblastoid and epithelioid
      morphology. In most of the cultures, cell proliferation occurred in the first
      week, but after the second week only some cultures - derived from the method
      without the Ficoll-Paque gradient density-maintained the growth rate reaching
      confluence. Those cultures were submitted to trypsinization with 0.25%
      trypsin/EDTA solution and cultured for two to three months. CONCLUSION: In the
      samples analyzed, cell separation and mesenchymal stem cell culture techniques
      from human umbilical cord blood by the method without the Ficoll-Paque density
      gradient was more efficient than the method with the Ficoll-Paque density
      gradient.

PMID- 18719826
TI  - [The use of the vancomycin paste for sternal hemostasis and mediastinitis
      prophylaxis].
AB  - INTRODUCTION: Mediastinitis is one of the most feared complications for thoracic
      surgeons, being a significant factor in morbidity and mortality in thoracic
      surgery. OBJECTIVE: To find a new alternative in order to prevent mediastinitis,
      reducing the morbidity and mortality. METHODS: A retrospective study including
      1020 patients operated between February 2002 and October 2005. Patients underwent
      bypass surgery and vancomycin paste was used rather than bone wax in all cases.
      RESULTS: Patients were followed-up for 45 months; there were only five (0.49%)
      cases of mediastinitis; no deaths were observed. CONCLUSION: The use of
      Vancomycin paste to replace bone wax proved to be a great allied to prevent
      mediastinitis after thoracic surgery.

PMID- 18719827
TI  - [Off-pump myocardial revascularization in the elderly: analysis of morbidity and
      mortality].
AB  - OBJECTIVE: To analyze the in-hospital outcome of elderly patients aged 70 years
      and older who underwent off-pump coronary artery bypass graft surgery with an
      intraluminal shunt in urgent, emergent, and elective coronary revascularizations.
      METHODS: From July 1989 to July 2005, we analyzed 87 patients ranging in age from
      70 to 92 years. Of the 87 patients enrolled, 50 (57.5%) patients had unstable
      angina, with three (3.4%) acute myocardial infarction; thirty-one (35.6%)
      patients underwent urgent and emergent surgery; thirteen (14.9%) patients had
      myocardial infarction in less than 30 days, and 34 (39.1%) in more than 30 days.
      RESULTS: The main postoperative complications were: atrial fibrillation (32.2%),
      heart failure (12.6%), pneumonia (10.3%), septicemia (3.4%), acute myocardial
      infarction (2.3%), mediastinitis (1.1%) transient ischemic attack (1.1%), and
      pneumothorax (1.1%). The mean extubation time was 18.50+/-19.09 hours, the length
      of stay in the intensive care unit was 2.92+/-2.03 days, and hospital length of
      stay was 10.55+/-7.16 days. Packed red cells were given to nine (10.34%) patients
      and none of them was operated due to bleeding. The in-hospital mortality was
      4.6%. CONCLUSIONS: In patients over 70 years-old, elective and non-elective off
      pump coronary artery bypass grafting with intracoronary shunt showed to be safe
      and effective, associated with low rates of postoperative complications and
      mortality in relation to the studied population.

PMID- 18719828
TI  - [Cell therapy plus transmyocardial laser revascularization: a proposed
      alternative procedure for refractory angina].
AB  - OBJECTIVE: We tested the hypothesis that TMLR combined with intramyocardial
      injection of BMC is safe, and may help increase the functional capacity of
      patient with refractory angina. METHODS: Nine patients (eight men), 65+/-5 years
      old, with refractory angina for multivessel disease and previous myocardial
      revascularization procedures (CABG/PCI), not candidates for another procedure due
      to the extension of the disease were enrolled. TMLR (11+/-3 laser drills) was
      performed via a limited thoracotomy using a CO2 Heart Laser System. BMC were
      obtained immediately prior to surgery, and the lymphomonocytic fraction separated
      by density gradient centrifugation. During surgery, 5 mL containing approximately
      1.9+/-0.3 x 10(8) BMC were delivered by multiple injections in the ischemic
      myocardium. Before (B) and 6 months (6M) after the procedure, patient underwent
      clinical evaluation and myocardial perfusion assessment by cardiac magnetic
      resonance imaging (MRI) during pharmacological stress with dypiridamole. RESULTS:
      No major complications or deaths occurred during the procedure. One patient died
      after 2 years (non cardiac cause). There was a reduction in the ischemic score as
      assessed by MRI from 1.64+/-0.10 (B) to 0.88+/-0.09 (6M) (P=0.01). Clinically,
      there was a reduction in functional class of angina from 3.7+/-0.2 (B) to 1.3+/
      0.2 (6M) (P<0.0001). CONCLUSIONS: In this initial experience, the combined
      strategy of TMLR plus cell therapy appeared to be safe, and may have
      synergistically acted to reduce myocardial ischemia, with clinically relevant
      improvement in functional capacity. Provided these data are confirmed in a
      larger, randomized, controlled trial with longer follow-up, this strategy could
      be used as a novel therapeutic option for treating pt with refractory angina.

PMID- 18719829
TI  - [Strategies to reduce the use of blood components in cardiovascular surgery].
AB  - OBJECTIVE: The aim of this study is to evaluate the strategies adopted by our
      team to reduce the use of bloods components in patients undergoing cardiovascular
      surgical procedures. METHODS: Between October 2005 and January 2007, 101 patients
      were operated. Fifty-one (50.5%) were male and 50 (49.5%) female. Patients' age
      ranged from 13 to 80 years (mean of 50.76 years). The strategy consisted in using
      antifibrinolytics and normovolemic hemodilution, and reinfusion of all the blood
      remaining in the CPB circuit. RESULTS: Mean use of blood components was 1.45 UI,
      red blood cells; 0.75 UI, fresh frozen plasma; 0.89 UI, cryoprecipitate, and 1.43
      UI, platelet. Fifty-nine patients (58.4%) had not used blood components and 12
      (11.9%) patients used more than 4 UI of red blood cells. In 27 patients (26.7%)
      whose CPB time was higher than 120 minutes, 17 (63%) needed hemotransfusion.
      However, 3 (2.97%) developed coagulopathy and 2 (1.98%) needed reoperation due to
      bleeding. Of the three patients who developed coagulopathy, two were in the
      elderly subgroup. CONCLUSION: In the presented series, the measures adopted
      succeeded in reducing the need of hemotransfusion in the postoperative period of
      thoracic surgery. Patients with CPB time higher than 120 minutes tended to need
      hemotransfusion. The association of surgery in elderly patients and CPB time over
      120 minutes resulted in significantly greater use of blood components
      postoperatively.

PMID- 18719830
TI  - [IV Pulmonary trunk reversible banding: analysis of right ventricle acute
      hypertrophy in an intermittent loading experimental model].
AB  - OBJECTIVES: Adjustable pulmonary trunk (PT) banding device may induce a more
      physiologic ventricle retraining for the two-stage Jatene operation. This
      experimental study evaluates the acute hypertrophy (96 hours) of the right
      ventricle (RV) submitted to an intermittent pressure overload. METHODS: Five
      groups of seven young goats were distributed according to RV intermittent
      systolic overload duration (0, 24, 48, 72 and 96 hours). The zero-hour group
      served as a control group. Echocardiographic and hemodynamic evaluations were
      performed daily. After completing the training program for each group, the
      animals were sacrificed for water content and cardiac masses evaluation. RESULTS:
      There was a significant increase in RV free wall thickness starting with the 48
      hour group (p<0.05). However, a decreased RV ejection fraction, associated with
      an important RV dilation and a significant increase in the RV volume to mass
      ratio was observed at 24-hour training period, when compared to 96-hour period
      (p=0.003), with subsequent recovery throughout the protocol. A 104.7% increase in
      RV mass was observed in the 96-hour group, as compared to the control group, with
      no differences in water content between these two groups. The daily mean increase
      in RV mass during the study period was 21.6% +/- 26.8%. The rate of RV mass
      acquisition for the overall study period of intermittent systolic overload was
      0.084 g/h +/- 0.035 g/h. CONCLUSION: Intermittent PT banding has allowed a
      significant RV mass acquisition in the 96-hour trained group. No myocardial water
      content changes were observed in this group, suggesting an increased myocardial
      protein synthesis.

PMID- 18719831
TI  - [Aortic arch surgery with bilateral cerebral perfusion by isolation of
      brachiocephalic trunk and left carotid artery].
AB  - OBJECTIVE: To evaluate the results of a technique described by Carreira et al.
      using bilateral antegrade selective cerebral perfusion by isolating the
      brachiocephalic trunk and the left carotid artery. METHODS: Fifteen patients were
      operated between June 2005 and September 2007. Data analysis were performed using
      Epi Info and statistical significance was set at p<0.05. RESULTS: Of the 15
      patients, 53.3% were male; mean age was 59.86+/-15.4 years; 60% presented with
      type A acute aortic dissection; 6.7% type B; and 33.3% aneurysm of aorta and
      arch. Mean CPB and aortic clamping time was 177.6+/-39.4 and 135.9+/-34.0
      minutes, respectively. In this group, 86.7% were not submitted to total
      circulatory arrest, with mean unilateral and bilateral selective cerebral
      perfusion time of 10.9+/-2.0 and 57.2+/-21.2 minutes, respectively. Mean
      hypothermic temperature was 23.0+/-2.9 masculineC. Two had left subclavian artery
      ligature, 60% used separated aortic grafts, and four used aortic endoprosthesis.
      Three (20%) patients died, all of them in the acute aortic dissection group.
      There were no neurological complications. The mean follow up time was 11.7+/-9.6
      months. Regarding mortality, none of the parameters were statistically
      significant (p>0.05). CONCLUSION: The technique of bilateral selective cerebral
      perfusion described by Carreira et al. can be performed by others and presents
      similar results to the international literature. The excellent neurological
      outcome and easy bleeding control on surgical sutures lines are the major
      advantages of this new procedure.

PMID- 18719832
TI  - [Adult cardiopulmonary bypass in the twentieth century: science, art or
      empiricism?].
AB  - The aim of the present review is to highlight some less discussed aspects of the
      cardiopulmonary bypass (CPB), taking into consideration the physiology,
      physiopathology, and some new technologies of perfusion. Thus, some points, to a
      certain extent philosophical, have motivated this revision: a) To preserve and
      update the surgeon knowledge regarding CPB, even to keep his/her pedagogical
      leadership on his/her surgical team; b) To question if elderly and diabetic
      patients, as a result of their individual characteristics deserve more
      appropriate protocols similar to those adopted for children; c) One third aspect
      would be the questioning of the systemic inflammatory reaction caused by the
      blood exposure to CPB non-endothelized circuit surface, in face of the increasing
      importance of blood contact with the surgical wound; d) In relation to the
      treatment of the vasoplegic syndrome, methylene blue continues being the best
      therapeutical option, even so, many times are not efficient on account of a
      highly probable existence of a "therapeutical window" based on the guanylate
      cyclase dynamics of action (saturation and synthesis "de novo") and; finally, e)
      The reason of the title, highlighting that based on its current patterns, would
      the CPB be an outcome of empiricism, art, or science? The bottom line of this
      article carries the certainty of that as much as the empiricism, art, and science
      are highly related to CPB.

PMID- 18719833
TI  - [Percutaneous aortic aortic valve replacement: myth or reality?].
AB  - Aortic valve replacement with mechanical or biological prosthesis with
      extracorporeal circulation is the gold-standard for the treatment of calcific
      aortic stenosis. Although the results are excellent with the conventional
      approach some elderly patients, with multiple high-risk comorbid conditions,
      reoperations and severe left ventricular dysfunction have high surgical risk.
      During the last years percutaneous techniques have been developed. The present
      study aim to analyse the literature, since the experimental development until
      clinical application of this novel treatment in patients with high surgical risk
      aortic stenosis. Percutaneous implantation of aortic valve prosthesis is being
      done in some centers and the cardiovascular surgeon that treats valve disease
      should be involved in this development.

PMID- 18719834
TI  - [Myocardial protection to the hypertrophied heart: the eternal challenge].
AB  - The myocardial protection allowed great advance in cardiac surgery, decreasing
      the mortality and making more feasible complex surgeries. Lately, the patient
      population elected for cardiac procedures has been changing towards elderly
      patients with ventricular function depressed and myocardial hypertrophy. The
      myocardial hypertrophy condition represents a great challenge since the beginning
      of the cardiac surgery. Several techniques have been described to protect the
      myocardial hypertrophy, however with no satisfactory results. In this manuscript
      we present the state of the art technique of myocardial protection.

PMID- 18719835
TI  - [Redering of accounts].

PMID- 18719836
TI  - [Project of international cooperation in pediatric heart surgery: actors:
      National Institute of Cardiology (INC) and Republic Islamic Algerian].

PMID- 18719837
TI  - [Radial artery harvesting technique without hemostatic clips and clinical
      experience].
AB  - OBJECTIVE: The various techniques of radial artery (RA) harvesting produce
      similar results. These techniques use electrocautery, ultrasonic scalpel, or
      sharp scissors in different combinations, but usually associated with the use of
      hemostatic clips. We describe a RA harvesting technique with the combination of
      sharp scissors and electrocautery without the use of hemostatic clips. METHODS:
      We describe a retrospective study of 107 patients ranging from 28 and 78 years of
      age (mean +/- SD; 53.3 +/- 8 yrs). Bleeding, re-operation, infarct, and death
      were analyzed. RESULTS: No bleeding was imputable to the RA and no re-operations
      were required. There were three (2.8%) infarcts possibly related to the RA
      anastomosis territory. Mortality was 0.9%, but unrelated to cardiac
      complications. CONCLUSION: RA electrocautery harvesting without hemostatic clips
      presented no bleeding and was an inexpensive procedure, requiring no investments
      in additional equipment.

PMID- 18719838
TI  - [Surgical ablation of atrial fibrillation using radiofrequency].
AB  - OBJECTIVE: To evaluate the effectiveness of intraoperative atrial fibrillation
      ablation using radiofrequency during mitral valve procedure. This report
      describes the early and midterms results. METHODS: Between September 2003 and
      September 2005, 15 patients with mitral disease were operated. All patients were
      in chronic atrial fibrillation and with congestive symptoms despite full
      medication. The patients were analysed according to clinical criteria, electrical
      and echocardiographic findings. RESULTS: There were no hospital mortality or
      complications related to radiofrequency ablation. The mean follow-up period was
      12.16 +/- 10.29 months. All patients left operating room in sinus rhythm,
      however, before hospital discharge, only nine (60%) were in regular cardiac
      rhythm. During follow-up, two patients presented atrial fibrillation recurrence
      and currently seven (46.7%) keep sinus rhythm. CONCLUSION: Despite low
      morbimortality related to the procedure, initial results in this report showed a
      less effectiveness of this technique when compared with other papers.

PMID- 18719839
TI  - [Intrapericardic surgical treatment of teratoma in an infant].
AB  - The intrapericardic cardiac tumors are infrequent; however, the clinical
      manifestations can be serious, even with symptoms of low cardiac output or
      cardiogenic shock, depending on the localization of the tumor. We report the case
      of a 3-month-old infant who progressed to cardiogenic shock due to an
      intrapericardic tumor compressing the right atrium and the vena cava superior.
      Emergent surgery for resection of the tumor mass was recommended. The patient had
      a 6-month uneventful postoperative course.

PMID- 18719840
TI  - [Coronary aneurysm after drug-eluting stent implantation].
AB  - The use of drug-eluting stents aiming at by-pass the disadvantage of stainless
      steel stents have been associated to late thrombosis after withdrawal of anti
      platelet agents. We report a case with another complication, the development of a
      coronary aneurysm in the stent area more than three years after index procedure.
      Late chronic local inflammatory responses may be responsible for the weakening,
      erosion and aneusrysm formation.

PMID- 18719841
TI  - [Bilateral ostial coronary lesion in cardiovascular syphilis: case report].
AB  - Syphilis is an infectious disease occurring through a series of frequently
      overlapping stages. It can impair the cardiovascular and neurological system. In
      30% of the non treated patients, syphilis develops its tertiary form. We report a
      case of a 46-year-old male patient admitted due to edema pulmonary and acute
      coronary syndrome with left bundle branch block, submitted to fibrinolytic
      therapy successfully. Coronary angiography showed a 90% ostial lesion of left
      main coronary artery and occlusion of the right coronary artery ostium. VDRL was
      titrated to 1/128. The patient was undergone to CABG and was discharged after
      treatment with crystalline penicillin.

PMID- 18719842
TI  - [Right atrium myxoid chondrosarcoma].
AB  - We report a case of a 46 years-old woman, Caucasian, with hypertension and a
      primary diagnosis of infectious endocarditis. A transthoracic echocardiogram was
      performed suggesting right atrium myxoma. The patient was submitted to surgery,
      which found a tumor mass with a jelly-like exterior. The mass was sent to anatomo
      pathological analysis which diagnosed a myxoid chondrosarcoma tumor. After
      surgical resection, the patient achieved complete recovery with no signs of
      recidivation after 14 months.

PMID- 18719843
TI  - [Agenesis of the right superior vena cava associated with total heart block].
AB  - The superior left vena cava with the absent superior vena cava is a rare
      abnormality, especially when associated with total heart block. We report a case
      of a patient in which the presence of superior left vena cava and the absence of
      the superior vena cava was detected during the implantation of a pacemaker for
      the correction of a total heart block, which led us to use a different technique
      for the fixation of the ventricular electrode. To confirm the supposed absence,
      several image exams were made showing the difficulty on the diagnosis of the
      described syndrome.

PMID- 18719844
TI  - [Solitary fibrous tumor in a child's heart].

PMID- 18719845
TI  - [Right ventricle and tricuspid valve myxoma].

PMID- 18719846
TI  - [Cardiopulmonary and heart transplantation: 100 years of history and 40 years of
      existence].

PMID- 18719847
TI  - [Ethic corporativism].

PMID- 18719849
TI  - Beliefs about mental health problems and help-seeking behavior in Dutch young
      adults.
AB  - BACKGROUND: Mental health problems in young adults are frequent and impairing,
      but are often left untreated. This study among young adults with self-perceived
      mental health problems examines beliefs about mental health problems (i.e. their
      cause, consequences, timeline, and controllability) and help-seeking behaviour.
      METHOD: A cross-sectional population survey (n = 2,258) in the south-west
      Netherlands. Participants were included who reported having mental health
      problems during the past year (n = 830). Beliefs about cause, consequences,
      timeline, and controllability of self-perceived mental health problems were
      assessed with the Illness Perception Questionnaire. Internalizing and
      externalizing psychopathology was assessed with the Adult Self-Report. RESULTS: A
      multivariate logistic regression analysis indicates that independent of sex, age,
      and severity of psychopathology, higher levels on the intra-psychic causes scale
      (OR = 1.95, 95%CI = 1.48-2.58), the consequences scale (OR = 1.81, 95%CI = 1.40
      2.33), and the treatment control scale (OR = 1.97, 95%CI = 1.60-2.41) are
      associated with an increased likelihood of mental health service use, while
      higher levels of personal control (OR = 0.76, 95%CI = 0.62-0.93) are associated
      with a decreased likelihood. CONCLUSIONS: Beliefs that may encourage young adults
      with mental health problems to seek professional help include the beliefs that
      mental health problems have adverse consequences and that treatment can help.
      Since these beliefs are related to young adults' knowledge of mental health
      problems, help-seeking behavior may be encouraged by educating young adults about
      mental health problems and the effective mental health treatments which are
      available.

PMID- 18719851
TI  - CIRSE 2008. Abstracts of the annual meeting of the Cardiovascular and
      Interventional Radiological Society of Europe. September 13-17, 2008. Copenhagen,
      Denmark.

PMID- 18719852
TI  - A complexity-based method for predicting protein subcellular location.
AB  - A complexity-based approach is proposed to predict subcellular location of
      proteins. Instead of extracting features from protein sequences as done
      previously, our approach is based on a complexity decomposition of symbol
      sequences. In the first step, distance between each pair of protein sequences is
      evaluated by the conditional complexity of one sequence given the other.
      Subcellular location of a protein is then determined using the k-nearest neighbor
      algorithm. Using three widely used data sets created by Reinhardt and Hubbard,
      Park and Kanehisa, and Gardy et al., our approach shows an improvement in
      prediction accuracy over those based on the amino acid composition and Markov
      model of protein sequences.

PMID- 18719853
TI  - Archaeal chromatin proteins histone HMtB and Alba have lost DNA-binding ability
      in laboratory strains of Methanothermobacter thermautotrophicus.
AB  - Alignments of the sequences of the all members of the archaeal histone and Alba1
      families of chromatin proteins identified isoleucine residues, I19 in HMtB and
      I39 in MtAlba, in Methanothermobacter thermautotrophicus, at locations predicted
      to be directly involved in DNA binding. In all other HMfB family members, residue
      19 is an arginine (R19), and either arginine or lysine is present in almost all
      other Alba1 family members at the structural site equivalent to I39 in MtAlba.
      Electrophoretic mobility shift assays revealed that recombinant HMtB and MtAlba
      do not bind DNA, but variants constructed with R19 and R39, respectively, bound
      DNA; and whereas MtAlba(I19) did not bind RNA, MtAlba(R19) bound both single
      stranded RNA and tRNA. Amplification and sequencing of MT0254 (encodes HMtB) and
      MT1483 (encodes MtAlba) from several Methanothermobacter thermautotrophicus
      lineages has revealed that HMtB and MtAlba had arginine residues at positions 19
      and 39, respectively, in the original isolate and that spontaneous mutations must
      have occurred, and been fixed, in some laboratory lineages that now have
      HMtB(I19) and MtAlba(I39). The retention of these variants suggests some
      continuing functions and fusion of the HMtB(I19) sequence to HMtA2 resulted in a
      protein that folds to form a histone fold heterodimer that binds and compacts
      DNA. The loss of DNA binding by HMtB(I19) does not therefore prevent HMtB from
      participating in DNA interactions as one partner of an archaeal histone
      heterodimer.

PMID- 18719854
TI  - Sulfobacillus benefaciens sp. nov., an acidophilic facultative anaerobic
      Firmicute isolated from mineral bioleaching operations.
AB  - Gram-positive bacteria found as the sole Firmicutes present in two mineral
      bioleaching stirred tanks, and a third bacterium isolated from a heap leaching
      operation, were shown to be closely related to each other but distinct from
      characterized acidophilic iron- and sulfur-oxidizing bacteria of the genus
      Sulfobacillus, to which they were affiliated. One of the isolates (BRGM2) was
      shown to be a thermo-tolerant (temperature optimum 38.5 degrees C, and maximum 47
      degrees C) obligate acidophile (pH optimum 1.5, and minimum 0.8), and also noted
      to be a facultative anaerobe, growing via ferric iron respiration in the absence
      of oxygen. Although isolates BRGM2 and TVK8 were able to metabolize many
      monomeric organic substrates, their propensity for autotrophic growth was found
      to be greater than that of Sulfobacillus thermosulfidooxidans and the related
      acidophile, Sb. acidophilus. Faster growth rates of the novel isolates in the
      absence of organic carbon was considered to be a major reason why they, rather
      than Sb. thermosulfidooxidans (which shared many physiological characteristics)
      more successfully exploited conditions in the stirred tanks. Based on their
      phylogenetic and phenotypic characteristics, the isolates are designated strains
      of the proposed novel species, Sulfobacillus benefaciens, with isolate BRGM2
      nominated as the type strain.

PMID- 18719855
TI  - Nimbolide a limonoid from Azadirachta indica inhibits proliferation and induces
      apoptosis of human choriocarcinoma (BeWo) cells.
AB  - We investigated the cytotoxic effects of nimbolide, a limonoid present in leaves
      and flowers of the neem tree (Azadirachta indica) on human choriocarcinoma (BeWo)
      cells. Treatment with nimbolide resulted in dose- and time-dependent inhibition
      of growth of BeWo cells with IC(50) values of 2.01 and 1.19 microM for 7 and 24 h
      respectively, accompanied by downregulation of proliferating cell nuclear
      antigen. Examination of nuclear morphology revealed fragmentation and
      condensation indicating apoptosis. Increase in the generation of reactive oxygen
      species (ROS) that was reversed by addition of reduced glutathione suggested ROS
      involvement in the cytotoxicity of nimbolide. A decrease in Bcl-2/Bax ratio with
      increased expression of Apaf-1 and caspase-3, and cleavage of poly(ADP-ribose)
      polymerase provide compelling evidence that nimbolide-induced apoptosis is
      mediated by the mitochondrial pathway. The results of the present study suggest
      that nimbolide has immense potential in cancer prevention and therapy based on
      its antiproliferative and apoptosis inducing effects.

PMID- 18719856
TI  - Surgical resection and permanent iodine-125 brachytherapy for brain metastases.
AB  - PURPOSE: To evaluate the efficacy and toxicity of surgical resection and
      permanent iodine-125 brachytherapy without adjuvant whole brain radiation therapy
      (WBRT) for brain metastases. METHODS AND MATERIALS: Forty patients were treated
      with permanent iodine-125 brachytherapy at the time of resection of brain
      metastases from 1997 to 2003. Actuarial freedom from progression (FFP) and
      survival were measured from the date of surgery and estimated using the Kaplan
      Meier method, with censoring at last imaging for FFP endpoints. RESULTS: The
      median survival was 11.3 months overall, 12.0 months in 19 patients with newly
      diagnosed brain metastases and 7.3 months in 21 patients with recurrent brain
      metastases. Twenty-two patients (55%) remained free of progression of brain
      metastases, three failed at the resection cavity (including one with
      leptomeningeal dissemination), two failed with leptomeningeal spread only, and 13
      failed elsewhere in the brain including two who also had leptomeningeal disease.
      The 1-year resection cavity FFP probabilities were 92%, 86% and 88%; and brain
      FFP probabilities were 29%, 43% and 37% for the newly diagnosed, recurrent and
      all patients, respectively. Symptomatic necrosis developed 7.4-40.0 months
      (median, 19.5 months) after brachytherapy in 9 patients (23%), confirmed by
      resection in 6 patients. CONCLUSIONS: Excellent local control was achieved using
      permanent iodine-125 brachytherapy for brain metastasis resection cavities,
      although there is a high risk of radiation necrosis over time. These data support
      consideration of permanent brachytherapy without adjuvant WBRT as a treatment
      option in patients with symptomatic or large newly diagnosed or recurrent brain
      metastases.

PMID- 18719857
TI  - Zhangfei induces the expression of the nerve growth factor receptor, trkA, in
      medulloblastoma cells and causes their differentiation or apoptosis.
AB  - Interactions between nerve growth factor (NGF) and its receptor-the tropomyosin
      related kinase A (trkA)-regulate many neuronal functions including the correct
      development of sensory neurons during embryogenesis, the survival of sensory
      neurons and the differentiation and apoptosis of neuronal tumours. Zhangfei is a
      transcriptional factor that is expressed in differentiated neurons. Since we
      could detect Zhangfei in mature neurons but not in neuronal tumour cells, we
      hypothesised that ectopic expression of the protein in medulloblastoma cells may
      induce the differentiation of these cells. We show that in ONS-76 medulloblastoma
      cells, resveratrol, an inducer of apoptosis and differentiation, increased the
      expression of Zhangfei, trkA and Early Growth Response Gene 1 (Egr1), a gene
      normally activated by NGF-trkA signalling. ONS-76 cells stopped growing soon
      after treatment with resveratrol. While the induction of Zhangfei in resveratrol
      treated cells was modest albeit consistent, the infection of actively growing
      medulloblastoma cells with an adenovirus vector expressing Zhangfei mimicked some
      of the effects of resveratrol. Ectopically expressed Zhangfei in ONS-76 cells led
      to the increased expression of trkA and Egr1, phosphorylation of extracellular
      signal-regulated kinase (Erk1), and caused ONS-76 cells to display markers of
      apoptosis. UW228, another medulloblastoma cell-line, was also susceptible to the
      suppressive effects of resveratrol and Zhangfei. In contrast, while resveratrol
      suppressed the growth of human diploid fibroblasts (MRC5), Zhangfei had
      relatively little effect on these cells.

PMID- 18719858
TI  - Embryonic and postnatal development in experimental tryptophan deprived rats. A
      preliminary study.
AB  - An ontogenetic and endocrinological study has been designed on developing rats in
      uterus of mothers tryptophan deprived at day 1 (exp. 1) and day 14.5 (exp. 2) of
      conception to verify the supposed determining role of the serotoninergic system
      (SS) in sexual differentiation in mammals. Tryptophan-free feeding has been
      pursued uninterruptedly in the litter after birth, during lactation and postnatal
      development. Tryptophan-free pregnant rats were obtained by exclusion of
      tryptophan sources from chow. In both exp. 1 and exp. 2 the litter showed at
      birth a significant physical under evolution, that worsened, during post-natal
      development, to a much more marked dwarfism in exp. 1 pups. At 30 days postnatal
      age, whereas the female exp. 1 rats showed a right-timed onset of puberty,
      neither descensus of the testes nor spermatogenesis could be observed in the male
      rats of the same experiment. Endocrinologically the males showed a significant
      reduction of plasma FSH levels, but also a slight increase of those of LH.
      Moreover, a marked hypoandrogenism and a severe hypoprolactinemia characterized
      the males of this group. Hypoprolactinemia was the major endocrinological finding
      also in the female litter, which, however, at 30 days p.n. age showed the typical
      histological patterns of a cycling ovary, i.e. growing secondary follicles with
      scattered antral spaces, and thus a right-timed pubertal maturation, in spite of
      the significant lower plasma levels of pituitary gonadotropins and sex steroids.
      When mothers were tryptophan deprived at 14.5 of pregnancy (exp. 2), the litters
      showed a less marked dwarfism, persistent, severe hypoprolactinemia as in exp. 1
      rats, but a normal right-timed onset of puberty in both male and female rats.
      Taken together these findings confirm on the one hand the close relationship
      between SS and PRL. On the other hand, they suggest a major, crucial role of PRL
      played in the male rat before day 14.5 of intrauterine development, presumably
      intervening in the synthesis of LH receptors sites by the maturing Leydig cells
      in the male gonads. Growth hormone concentrations in both sexes dwarf rats were
      lower than in control rats.

PMID- 18719859
TI  - A combination of zinc and pyridoxine supplementation to the diet of laying hens
      improves performance and egg quality.
AB  - The objective of this study was to investigate whether zinc, along with
      pyridoxine, is effective in improving performance and egg quality of laying hens.
      One hundred and twenty, 28-week-old Hy-Line laying hens were assigned to four
      treatment groups, 30 hens each. The birds were fed a basal diet or the basal diet
      supplemented with either 30 mg of zinc/kg of diet, 8 mg of pyridoxine/kg of diet,
      or 30 mg of zinc plus 8 mg of pyridoxine/kg of diet. Feed conversion (P < 0.01)
      and egg production (P < 0.01) improved most when both zinc and pyridoxine were
      supplemented to the diet. Eggshell weights were also greatest (P < 0.01) when the
      diet was supplemented with both pyridoxine and zinc. Egg-shape index was,
      however, greatest with zinc-supplemented diet (P < 0.004). Haugh unit was
      greatest in eggs of hens fed a diet supplemented with both zinc and pyridoxine (P
      < 0.01). Dietary zinc and pyridoxine supplementations together increased plasma
      calcium and phosphorous concentrations (P < 0.002). The results of the present
      study suggested that zinc (30 ppm) and pyridoxine (8 ppm) supplements, when used
      together, are recommended in terms of a better performance and egg quality in
      laying hens.

PMID- 18719860
TI  - Evaluation of allicin for the treatment of experimentally induced subacute lead
      poisoning in sheep.
AB  - Garlic (Allium sativum) is known to reduce lead toxicity in some species of
      animals. The objective of this study was to evaluate the efficacy of allicin, one
      of the most active components of garlic, in the treatment of subacute lead
      intoxication in sheep. Nine female sheep weighing 25-29 kg orally received a
      daily dose of 80 mg/kg body weight of lead acetate for 5 days. The animals were
      then assigned into two groups. Group 1 did not receive any further treatment and
      was used as the control group and group 2 was treated orally by 2.7 mg/kg body
      weight of allicin twice daily for 7 days. Within one day following allicin
      treatment, group 2 blood lead levels were significantly lower than that in group
      1 (mean of 616.9 microg/l and 290.02 microg/l, respectively; P < 0.05). Also,
      allicin treatment significantly reduced kidney lead content and considerably
      reduced bone and ovary lead contents. These results suggest that allicin might
      have some therapeutic effects on lead poisoning.

PMID- 18719861
TI  - Clinically relevant concentration determination of inhaled anesthetics
      (halothane, isoflurane, sevoflurane, and desflurane) by 19F NMR.
AB  - Biophysical studies of protein-anesthetic interactions using nuclear magnetic
      resonance (NMR) spectroscopy are often conducted by the addition of micro amounts
      of neat inhaled anesthetic which yields much higher than clinically relevant (0.2
      0.5 mM) anesthetic concentrations. We report a 19F NMR technique to measure
      clinically relevant inhaled anesthetic concentrations from saturated aqueous
      solutions of these anesthetics (halothane, isoflurane, sevoflurane, and
      desflurane). We use a setup with a 3-mm NMR tube (containing trifluoroacetic acid
      as standard), coaxially inserted in a 5-mm NMR tube containing anesthetic
      solution under investigation. All experiments are conducted in a 5-mm NMR probe.
      We also have provided standard curves for four inhaled anesthetics using NMR
      technique. The standard curve for each of these anesthetics is helpful in
      determining the prerequisite amount of aqueous anesthetic solution required to
      prepare clinically relevant concentrations for protein-anesthetic interaction
      studies.

PMID- 18719862
TI  - [Surgical therapy options in peritonitis: experiences with staged lavage].

PMID- 18719863
TI  - [Common bile duct stones. Diagnostic and therapeutic management].
AB  - The best predictors for the presence of common bile duct stones (CBDS) are
      cholangitis, jaundice, and direct visualization of stones with ultrasound. In the
      setting of high suspicion of choledocholithiasis, endoscopic retrograde
      cholangiography (ERC) is indicated because when CBDS are identified, it allows
      immediate therapy in the same sitting. If there is a moderate probability of
      choledocholithiasis, endosonography or magnetic resonance
      cholangiopancreatography are the first-line options. In patients with gallbladder
      stones and CBDS, preoperative ERC with or without endoscopic sphincterotomy (ES)
      is widely recommended as a standard approach. The interval between that and
      laparoscopic cholecystectomy (LC) should be at least 24 h (<6 weeks) to exclude
      possible complications due to the ERC/ES. In the setting of open cholecystectomy,
      open bile duct surgery is significantly superior to ERC with sphincterotomy in
      achieving common bile duct clearance and is the method of choice. Only in centres
      with advanced laparoscopic expertise is the laparoscopic removal of CBDS an
      equivalent treatment option.

PMID- 18719864
TI  - [Traumatology of the spine].
AB  - Spinal trauma poses considerable threats to survival and quality of life.
      Especially cervical spine injuries are often associated with neurologic deficits.
      A thorough diagnostic pathway, often including computed tomography with sagittal
      reconstruction, is mandatory to evaluate the extent and consequences of spinal
      trauma. Every treatment must aim to restore stability and prevent secondary
      neurologic deterioration. Compression fractures usually can be treated
      successfully with conservative treatment, while burst fractures usually, and
      flexion/distraction injuries, and fracture-dislocation generally require internal
      stabilization. Injuries of the upper cervical spine can be treated conservatively
      or operatively, depending on the degree of instability. In the lower cervical
      spine, most injuries require internal fixation.

PMID- 18719865
TI  - [Spontaneous retropharyngeal hematoma: a rare differential diagnosis of acute
      dysphagia].
AB  - Spontaneous retropharyngeal hematoma is a rare but potentially fatal disease. It
      occurs with no underlying medical condition such as trauma, hemorrhagic
      diathesis, or medically induced anticoagulation.We report a case of a 48-year-old
      man who presented with progressive dysphagia, signs of inflammation, and a
      reduced general health status. There was distinct hemorrhagic swelling of the
      posterior and lateral walls of the nasopharynx, oropharynx, and hypopharynx, as
      well as red discoloration of the neck. No underlying medical conditions,
      medications, or trauma were reported.In light of the current case and the
      available literature, we present the necessary diagnostic procedures and
      treatment options. Because the course of this disease might be fatal due to rapid
      airway obstruction and progressive internal blood loss, it is of utmost
      importance to keep this diagnosis in mind for differential diagnostic
      considerations.

PMID- 18719866
TI  - [Structured residency training program for otolaryngology: a trendsetting
      principle].
AB  - A concept for an ORL residency training program is necessary because of personnel
      bottlenecks, quality assurance and benchmarkings. We have created a 2.5 years'
      program, which is based on 6 pillars: 1. Acquisition of the necessary specialist
      knowledge by the resident in self-study. 2. Weekly attendance of training
      lectures according to a study timetable, a monthly specialist seminar to discuss
      case examples. 3. Weekly presentation by the resident on an article from the
      current literature, alternating with a presentation on cases and a morbidity and
      mortality conference. 4. Annual 60 min learning target test. 5. Definition of a
      surgical training calendar oriented to the new national ORL training regulations.
      6. Internal operation course with preparative exercises in anatomy and visit to
      an operations course at a renowned otolaryngology clinic each year. After 2.5
      years of the training time a revision course is introduced. In this way a basic
      training will be guaranteed for all residents, which can be assessed by the
      annual test. Finally, the construction of a further training curriculum should
      lead to an improved transparent training, a higher standard of quality and
      improved staff satisfaction.

PMID- 18719867
TI  - [Local botulinum toxin A for treating chronic sialorrhea].
AB  - BACKGROUND: Sialorrhea and drooling interfere with oral communication and
      nutrition, posing problems for hygiene, nursing, and social interactions.
      Therapeutic efforts such as swallowing therapy, systemic medications, operations,
      and irradiation are often insufficient or accompanied by side effects. MATERIALS
      AND METHODS: Ten patients with therapy-resistant sialorrhea of various etiologies
      were treated between 2002 and 2007 with sonography-guided botulinum toxin A (BTA)
      injections into the parotid and submandibular glands bilaterally. Therapeutic
      success was evaluated using established symptom scores, and the glandular tissue
      size was sonographically measured before and 3 months after injections. RESULTS:
      All 10 patients benefited from the BTA therapy, as shown by significant reduction
      of the troublesome sialorrhea. The effect lasted 6-28 weeks. On one occasion,
      transient xerostomia occurred. Sonographic measurements revealed no morphologic
      changes. CONCLUSION: BTA is an effective and safe treatment for chronic
      sialorrhea. The effect is reversible. It causes no sonographically detectable
      changes.

PMID- 18719868
TI  - [Application of skin adhesives in head and neck surgery: analysis of cosmetic
      results, applicability and cost-effectiveness of cyanoacrylate-based adhesives].
AB  - BACKGROUND: In this work cyanoacrylate-based skin adhesives used in Germany for
      skin closure in head and neck surgery are compared with respect to ease of
      application, cost-effectiveness and cosmetic results. PATIENTS AND MATERIALS: We
      compared 25 wounds sealed with a skin adhesive with 25 suture-sealed wounds.
      RESULTS: Bonding of surgical wounds with glue had a high level of acceptance in
      all patients. The tedious, time-consuming and sometimes painful postoperative
      removal of many sutures in patients is omitted. Patients can shower soon
      afterwards without additional protection as the adhesive provides a waterproof
      barrier. Problems of wound healing can immediately be detected through the
      transparent skin adhesive. Cosmetic long-term results of skin closure by
      adhesives are comparable to suture-sealed wounds. CONCLUSIONS: The adhesives
      available on the market differ mainly in the form of the applicator, the
      viscosity on application, as well as the strength after hardening. The
      application is easy to implement and significantly faster than conventional
      suturing. Apart from the cost savings of materials compared to the use of skin
      sutures and investment of Steri-Strips, expensive anesthesia and surgical time
      can also be saved.

PMID- 18719869
TI  - [Fibrinogen/LDL apheresis for treatment of sudden hearing loss: an observational
      study on 152 patients].
AB  - Disturbances of cochlear microcirculation are among the most discussed causes of
      sudden sensorineural hearing loss. Increased levels of cholesterol and fibrinogen
      seem to act as risk factors for inner ear disorders. Fibrinogen/LDL apheresis
      greatly reduces the concentration of plasma fibrinogen thus leading to improved
      cochlear blood flow. In a retrospective case series remission rates of 152
      patients suffering from sudden sensorineural hearing loss and resistant to former
      treatment were investigated after treatment with a single apheresis. Complete
      remission was reported in 11% of patients, partial remission in 43%. 37% had no
      change of hearing threshold and 2% reported a decrease in hearing. Rates of
      complete remissions decreased from 22% within the first 2 weeks after onset of
      hearing loss to 14% after 6 weeks. In the same period of time rates of partial
      remissions decreased from 33% to 13%. The present study shows that apheresis
      achieved complete or partial remission in 54% of patients even after unsuccessful
      treatment with another therapy and the therapeutic window lies by approximately 6
      weeks.

PMID- 18719870
TI  - [The problem of hearing threshold assessment in objective audiometry].

PMID- 18719871
TI  - [Cervicoproprioceptive provocation of horizontal and vertical nystagmus in test
      subjects].
AB  - BACKGROUND: The cervico-ocular reflex (COR) has been confirmed in numerous animal
      experiments. On the other hand, its clinical assessment is disputed. Anteflexion
      and retroflexion of the head are among the main movements of the atlanto
      occipital joint. We investigated whether these head movements produce neck
      proprioceptive stimulation in the vestibular system. SUBJECTS AND METHOD: We
      investigated 50 students under the experimental conditions of strictly cervical
      provocation. The trunk was rotated, anteflexed, and retroflexed into its end
      positions for 60 s under video-oculographic control without changing the head
      space relationship. During the cervical provocation, horizontal, vertical, or
      rotational nystagmus within a time window of 5-30 s after the start of the
      provocation was detected as a target parameter. RESULTS: The results showed that,
      compared to the baseline, there was a significant increase in vertical and
      horizontal nystagmus after the cervical provocation. The horizontal nystagmus
      reaction, rather than the vertical, was increased significantly by the maximum
      trunk rotation. In addition, we found a significant amount of vertical rather
      than horizontal nystagmus under trunk flexion provocation. CONCLUSION: Under
      cervical provocation of test subjects, we were able to elicit horizontal and
      vertical nystagmus (upbeat nystagmus) via cervico-ocular roots. Due to a neck
      proprioceptive activation of the vestibular system we interpret our result as a
      "cervico-tonic provocation nystagmus".

PMID- 18719872
TI  - [A 49-year-old woman with deep vein thrombosis, pulmonary embolism, and left
      sided paralysis].
AB  - We report the case of a 49-year-old female patient who was admitted stationary
      because of a left-sided paralysis which had appeared some hours before. An
      embolic occlusion of the right A. cerebri media turned out to be the cause. A
      paradoxical embolism could be assumed because of an existing deep vein thrombosis
      and an increased right-ventricular pressure within a hemodynamically relevant
      fulminant pulmonary embolism as well as the additional existence of a patent
      foramen ovale (PFO). Systemic lysis as treatment of the pulmonary embolism was
      contraindicated because slight bleeding had occurred in the area of the right
      basal ganglia after treatment of the embolic occlusion of the right A. cerebri
      media by a local lysis. Subsequently and in the acuteness, a catheter
      interventional PFO-closure via a double-umbrella device was placed and the
      pulmonary embolism was effectively treated by a local lysis through the insertion
      of a pigtail-catheter into the right pulmonary artery.

PMID- 18719873
TI  - [Gastrointestinal diseases and osteomalacia].
AB  - Osteomalacia is a metabolic bone disease associated with impaired mineralization
      of the bone due to Vitamin D and Calcium deficiency that can develop in
      gastrointestinal disorders. Gastrointestinal malabsorption after surgery, in
      disorders of the small bowl, in diseases of the hepatobiliary tree and in
      pancreatic insufficiency can lead to decreased enteral resorption of the fat
      soluble Vitamin D and/or depletion of endogenous Vitamin D stores due to abnormal
      enterohepatic circulation. As a consequence of the Vitamin D deficiency in
      combination with the underlying condition patients develop an impaired calcium
      absorption resulting in hypocalcaemia, which leads to defective bone
      mineralization. Additionally chronic gastrointestinal inflammation and
      corticosteroid therapy - which is often needed in these patients - have a
      negative effect on bone metabolism as well. The therapy consists of oral
      substitution of Vitamin D and Calcium as well as sufficient sun light exposure or
      in severe cases the use of artificial UVB-radiation.

PMID- 18719874
TI  - [Indications and results of kypho- and vertebroplasty].
AB  - The best currently available evidence based treatment reduces vertebral fracture
      risk but does not totally prevent osteoporotic and malignant follow-up fractures.
      Kyphoplasty and vertebroplasty are options of a causal treatment to reduce pain
      by internal stabilization of fractured vertebrae. The indication for these
      minimal invasive procedures requires an interdisciplinary discussion of the
      individual case to guarantee technical feasibility, to increase the likelihood
      that these procedures will indeed reduce pain and to embed these procedures into
      the long term therapeutic concept of every single patient. In addition to
      internal stabilization of a painfully fractured vertebra kyphoplasty also seeks
      to restore lost vertebral height which appears promising in acute vertebral
      fractures. Due to the procedure there are more cement leakages after
      vertebroplasty. Available controlled prospective studies demonstrate only for
      kyphoplasty a long-term benefit for the patient in terms of pain reduction,
      increased mobility and improved quality of life.

PMID- 18719875
TI  - Middle-Eocene artiodactyls from Shanghuang (Jiangsu Province, Coastal China) and
      the diversity of basal dichobunoids in Asia.
AB  - A new assemblage of basal dichobunoid artiodactyls from the middle-Eocene
      Shanghuang fissure fillings includes the diacodexeid Jiangsudon shanghuangensis
      gen. and sp. nov., a new species of the lantianine dichobunoid Elaschitotherium,
      Elaschitotherium crepaturus sp. nov., and an indeterminate suoid which is
      presently the earliest record of this clade. Diacodexeids are also represented by
      two forms provisionally referred to cf. Diacodexis sp. and to an indeterminate
      Diacodexeidae, respectively. The occurrence of diacodexeids in Shanghuang
      contrasts with the early and earliest middle-Eocene chronological range of the
      family in Europe and North America and suggests that the stratigraphic range of
      the family in Asia extends up to the middle Eocene. This may reflect particular
      habitats in coastal China that may have been relatively stable during the early
      and middle Eocene, thus preserving forest-dwelling artiodactyls that became
      extinct in the other Holarctic regions. Compared to other supposedly coeval North
      American, European, and Asian faunas, the Shanghuang mammalian assemblage is most
      similar to early Uintan faunas of North America but is also remarkable in
      recording forms close to taxa that are characteristic of the Wasatchian and
      Bridgerian North American Land Mammal Ages. The Irdinmanhan age of the Shanghuang
      fauna is supported by the mammalian assemblage recovered from the fissure D, but
      an Arshantan age cannot be completely ruled out at this point. Although the
      Shanghuang assemblage is biased towards preservation of small components of the
      mammalian fauna, the Shanghuang fauna provide an important and unique window into
      the Eocene diversity and early evolution of cetartiodactyls in eastern Asia.

PMID- 18719876
TI  - [Automated procedure for volumetric measurement of metastases: estimation of
      tumor burden].
AB  - Cancer is a common and increasing disease worldwide. Therapy monitoring in
      oncologic patient care requires accurate and reliable measurement methods for
      evaluation of the tumor burden. RECIST (response evaluation criteria in solid
      tumors) and WHO criteria are still the current standards for therapy response
      evaluation with inherent disadvantages due to considerable interobserver
      variation of the manual diameter estimations. Volumetric analysis of e.g. lung,
      liver and lymph node metastases, promises to be a more accurate, precise and
      objective method for tumor burden estimation.

PMID- 18719877
TI  - Alterations in cytosine methylation and species-specific transcription induced by
      interspecific hybridization between Oryza sativa and O. officinalis.
AB  - Interspecific hybridization and polyploidization may involve programmed genetic
      and epigenetic changes. In this study, we used the methylation-sensitive
      amplified polymorphism (MSAP) method to survey cytosine methylation alterations
      that occurred in F(1) hybrid and BC(1) progeny following interspecific
      hybridization between Oryza sativa and O. officinalis. Across all 316 parental
      methylated sites, 25 (7.9%) cytosine methylation alterations were detected in the
      F(1) and/or BC(1) progeny. Thirty additional cytosine methylation alterations
      were detected at parental non-methylated or novel sites. In total, 55 cytosine
      methylation alterations (90.9% of all alterations) were detected in the F(1)
      hybrid, which were maintained in the BC(1) progeny. The alterations in cytosine
      methylation were biased toward the O. officinalis parent and were in some cases
      repeatable in independent hybridizations between O. sativa and O. officinalis.
      Twelve fragments showing cytosine methylation alterations were isolated,
      sequenced and subsequently validated by methylation-sensitive Southern blot
      analysis. Where possible, we designed species-specific primers to amplify the
      polymorphic transcripts from either the O. sativa or the O. officinalis parent
      using reverse transcription (RT)-PCR in combination with single-strand
      conformation polymorphism (SSCP) analysis. In four of five cases, modified gene
      expression could be correlated with the altered cytosine methylation pattern. Our
      results demonstrated cytosine methylation alterations induced by interspecific
      hybridization between a rice cultivar and its wild relative, and indicated a
      direct relationship between cytosine methylation alteration and gene expression
      variation.

PMID- 18719878
TI  - Genetic control of yield related stalk traits in sugarcane.
AB  - A major focus of sugarcane variety improvement programs is to increase sugar
      yield, which can be accomplished by either increasing the sugar content of the
      cane or by increasing cane yield, as the correlation between these traits is low.
      We used a cross between an Australian sugarcane variety Q165, and a Saccharum
      officinarum accession, IJ76-514, to dissect the inheritance of yield-related
      traits in the complex polyploid sugarcane. A population of 227 individuals was
      grown in a replicated field trial and evaluated over 3 years for stalk weight,
      stalk diameter, stalk number, stalk length and total biomass. Over 1,000 AFLP and
      SSR markers were scored across the population and used to identify quantitative
      trait loci (QTL). In total, 27 regions were found that were significant at the 5%
      threshold using permutation tests with at least one trait; individually, they
      explained from 4 to 10% of the phenotypic variation and up to 46% were consistent
      across years. With the inclusion of digeneic interactions, from 28 to 60% of the
      variation was explained for these traits. The 27 genomic regions were located on
      22 linkage groups (LGs) in six of the eight homology groups (HGs) indicating that
      a number of alleles or quantitative trait alleles (QTA) at each QTL contribute to
      the trait; from one to three alleles had an effect on the traits for each QTL
      identified. Alleles of a candidate gene, TEOSINTE BRANCHED 1 (TB1), the major
      gene controlling branching in maize, were mapped in this population using either
      an SSR or SNP markers. Two alleles showed some association with stalk number, but
      unlike maize, TB1 is not a major gene controlling branching in sugarcane but only
      has a minor and variable effect.

PMID- 18719879
TI  - Association mapping in multiple segregating populations of sugar beet (Beta
      vulgaris L.).
AB  - Association mapping in multiple segregating populations (AMMSP) combines high
      power to detect QTL in genome-wide approaches of linkage mapping with high
      mapping resolution of association mapping. The main objectives of this study were
      to (1) examine the applicability of AMMSP in a plant breeding context based on
      segregating populations of various size of sugar beet (Beta vulgaris L.), (2)
      compare different biometric approaches for AMMSP, and (3) detect markers with
      significant main effect across locations for nine traits in sugar beet. We used
      768 F(n) (n = 2, 3, 4) sugar beet genotypes which were randomly derived from 19
      crosses among diploid elite sugar beet clones. For all nine traits, the genotypic
      and genotype x location interaction variances were highly significant (P < 0.01).
      Using a one-step AMMSP approach, the total number of significant (P < 0.05)
      marker-phenotype associations was 44. The identification of genome regions
      associated with the traits under consideration indicated that not only
      segregating populations derived from crosses of parental genotypes in a
      systematic manner could be used for AMMSP but also populations routinely derived
      in plant breeding programs from multiple, related crosses. Furthermore, our
      results suggest that data sets, whose size does not permit analysis by the one
      step AMMSP approach, might be analyzed using the two-step approach based on
      adjusted entry means for each location without losing too much power for
      detection of marker-phenotype associations.

PMID- 18719880
TI  - Outcomes of surgical treatment of diabetic foot osteomyelitis: a series of 185
      patients with histopathological confirmation of bone involvement.
AB  - AIMS/HYPOTHESIS: We analysed the factors that determine the outcomes of surgical
      treatment of osteomyelitis of the foot in diabetic patients given early surgical
      treatment within 12 h of admission and treated with prioritisation of foot
      sparing surgery and avoidance of amputation. METHODS: A consecutive series of 185
      diabetic patients with foot osteomyelitis and histopathological confirmation of
      bone involvement were followed until healing, amputation or death. RESULTS:
      Probing to bone was positive in 175 cases (94.5%) and radiological signs of
      osteomyelitis were found in 157 cases (84.8%). Staphylococcus aureus was the
      organism isolated in the majority of cultures (51.3%), and in 35 cases (36.8%) it
      proved to be methicillin-resistant. The surgical treatment performed included 91
      conservative surgical procedures, which were defined as those where no amputation
      of any part of the foot was undertaken (49.1%). A total of 94 patients received
      some degree of amputation, consisting of 79 foot-level (minor) amputations
      (42.4%) and 15 major amputations (8%). Five patients died during the
      perioperative period (2.7%). Histopathological analysis revealed 94 cases (50.8%)
      of acute osteomyelitis, 43 cases (23.2%) of chronic osteomyelitis, 45 cases
      (24.3%) of acute exacerbation of chronic osteomyelitis and three remaining cases
      (1.6%) designated as 'other'. The risks of failure in the case of conservative
      surgery were exposed bone, the presence of ischaemia and necrotising soft tissue
      infection. CONCLUSIONS/INTERPRETATION: Conservative surgery without local or high
      level amputation is successful in almost half of the cases of diabetic foot
      osteomyelitis. Prospective trials should be undertaken to determine the relative
      roles of conservative surgery versus other approaches.

PMID- 18719881
TI  - Beta cell glucose sensitivity is decreased by 39% in non-diabetic individuals
      carrying multiple diabetes-risk alleles compared with those with no risk alleles.
AB  - AIMS/HYPOTHESIS: Novel type 2 diabetes-susceptibility loci have been identified
      with evidence that individually they mediate the increased diabetes risk through
      altered pancreatic beta cell function. The aim of this study was to test the
      cumulative effects of diabetes-risk alleles on measures of beta cell function in
      non-diabetic individuals. METHODS: A total of 1,211 non-diabetic individuals
      underwent metabolic assessment including an OGTT, from which measures of beta
      cell function were derived. Individuals were genotyped at each of the risk loci
      and then classified according to the total number of risk alleles that they
      carried. Initial analysis focused on CDKAL1, HHEX/IDE and TCF7L2 loci, which were
      individually associated with a decrease in beta cell function in our cohort. Risk
      alleles for CDKN2A/B, SLC30A8, IGF2BP2 and KCNJ11 loci were subsequently included
      into the analysis. RESULTS: The diabetes-risk alleles for CDKAL1, HHEX/IDE and
      TCF7L2 showed an additive model of association with measures of beta cell
      function. Beta cell glucose sensitivity was decreased by 39% in those individuals
      with five or more risk alleles compared with those individuals with no risk
      alleles (geometric mean [SEM]: 84 [1.07] vs 137 [1.11] pmol min(-1) m(-2)
      (mmol/l)(-1), p = 1.51 x 10(-6)). The same was seen for the 30 min insulin
      response (p = 4.17 x 10(-7)). The relationship remained after adding in the other
      four susceptibility loci (30 min insulin response and beta cell glucose
      sensitivity, p < 0.001 and p = 0.003, respectively). CONCLUSIONS/INTERPRETATION:
      This study shows how individual type 2 diabetes-risk alleles combine in an
      additive manner to impact upon pancreatic beta cell function in non-diabetic
      individuals.

PMID- 18719882
TI  - Plasma osteoprotegerin levels predict cardiovascular and all-cause mortality and
      deterioration of kidney function in type 1 diabetic patients with nephropathy.
AB  - AIMS/HYPOTHESIS: The bone-related peptide osteoprotegerin is produced by vascular
      cells and is involved in the process of vascular calcification. The aim of this
      study was to investigate the predictive value of plasma levels of osteoprotegerin
      in relation to mortality, cardiovascular events and deterioration in kidney
      function in patients with type 1 diabetes. METHODS: This prospective
      observational follow-up study included 397 type 1 diabetic patients with overt
      diabetic nephropathy (243 men; age [mean+/-SD] 42.1 +/- 10.6 years, duration of
      diabetes 28.3 +/- 9.9 years, GFR 67 +/- 28 ml min(-1) 1.73 m(2)) and a group of
      176 patients with longstanding type 1 diabetes and persistent normoalbuminuria
      (105 men; age 42.6 +/- 9.7 years, duration of diabetes 27.6 +/- 8.3 years).
      RESULTS: The median (range) follow-up period was 11.3 (0.0-12.9) years. Among
      patients with diabetic nephropathy, individuals with high osteoprotegerin levels
      (fourth quartile) had significantly higher all-cause mortality than patients with
      low levels (first quartile) (covariate-adjusted hazard ratio [HR] 3.00 [1.24
      7.27]). High osteoprotegerin levels also predicted cardiovascular mortality
      (covariate-adjusted HR 4.88 [1.57-15.14]). Furthermore, patients with high
      osteoprotegerin levels had significantly higher risk of progression to end-stage
      renal disease than patients with low levels (covariate-adjusted HR 4.32 [1.45
      12.87]). In addition, patients with high levels of plasma osteoprotegerin had an
      elevated rate of decline in GFR. CONCLUSIONS/INTERPRETATION: High levels of
      osteoprotegerin predict all-cause and cardiovascular mortality in patients with
      diabetic nephropathy. Furthermore, high levels of osteoprotegerin predict
      deterioration of kidney function towards end-stage renal disease.

PMID- 18719883
TI  - Transcriptional profiling of myotubes from patients with type 2 diabetes: no
      evidence for a primary defect in oxidative phosphorylation genes.
AB  - AIMS/HYPOTHESIS: Microarray-based studies of skeletal muscle from patients with
      type 2 diabetes and high-risk individuals have demonstrated that insulin
      resistance and reduced mitochondrial biogenesis co-exist early in the
      pathogenesis of type 2 diabetes independently of hyperglycaemia and obesity. It
      is unknown whether reduced mitochondrial biogenesis or other transcriptional
      alterations co-exist with impaired insulin responsiveness in primary human muscle
      cells from patients with type 2 diabetes. METHODS: Using cDNA microarray
      technology and global pathway analysis with the Gene Map Annotator and Pathway
      Profiler (GenMapp 2.1) and Gene Set Enrichment Analysis (GSEA 2.0.1), we examined
      transcript levels in myotubes established from obese patients with type 2
      diabetes and matched obese healthy participants, who had been extensively
      metabolically characterised both in vivo and in vitro. We have previously
      reported reduced basal lipid oxidation and impaired insulin-stimulated glycogen
      synthesis and glucose oxidation in these diabetic myotubes. RESULTS: No single
      gene was differently expressed after correction for multiple testing, and no
      biological pathway was differently expressed using either method of global
      pathway analysis. In particular, we found no evidence for differential expression
      of genes involved in mitochondrial oxidative metabolism. Consistently, there was
      no difference in mRNA levels of genes known to mediate the transcriptional
      control of mitochondrial biogenesis (PPARGC1A and NRF1) or in mitochondrial mass
      between diabetic and control myotubes. CONCLUSIONS/INTERPRETATION: These results
      support the hypothesis that impaired mitochondrial biogenesis is not a primary
      defect in the sequence of events leading to insulin resistance and type 2
      diabetes.

PMID- 18719884
TI  - [Value of adjuvant physiotherapy in postoperative pain management].
AB  - In times of limited financial and human resources the application of adjuvant
      physiotherapy postoperatively in orthopaedic patients requires reevaluation. In
      the early postoperative course physiotherapy improves the patients' mobility.
      However, it is not able to reduce the need for pain medication. It is intended to
      minimize complications and to mobilize and motivate the patients early. In
      contrast, massages are of minor importance in the immediate postoperative course
      and are applied only in a few selected cases. Cryotherapy plays a major role
      especially after shoulder and knee surgery. On the other hand, transcutaneous
      electrical nerve stimulation (TENS) and acupuncture are applied only in selected
      patients after orthopaedic surgery, e.g., after limb amputation.

PMID- 18719885
TI  - [On the biomechanics of the hip: relevance of femoral anteversion for hip contact
      force and loading using a short-stemmed prostheses].
AB  - Short-stemmed hip implants were established in total hip arthroplasty in the last
      years. Also patients with secondary osteoarthritis of the hip with pathological
      anteversion of the femoral neck are treated increasingly using this method.
      Therefore an investigation was performed to analyze the resulting hip contact
      force and femoral loading in the proximal femur at the solid model of the
      "standardized femur". Two different situations of femoral component anteversion
      were simulated. Increased hip contact forces and an increase of medial and
      lateral cortex loads result in the anteverted model. With present level of
      knowledge about the influence of the hip contact force the use of short-stemmed
      implants is not uncritically in patients with degenerative osteoarthritis of the
      hip combined with rotational disorders of the proximal femur. The selection of
      the tribological pairing is to be considered more strongly regarding the wear
      behavior.

PMID- 18719887
TI  - [Lateral retinacular release].
AB  - This overview of numerous studies discusses, based on short-term and long-term
      results, which diagnoses are indications for lateral retinacular release. No
      significant differences in outcome between arthroscopic and open lateral release
      could be documented. Isolated lateral release offers a good success rate for
      treating a stable patella with excessive lateral pressure. In patellar
      instability, the results are less favorable in long-term follow-up evaluation.
      Hyperlaxity with hypermobility of the patella is an absolute contraindication.
      Lateral release provides only temporary benefit for patellofemoral
      osteoarthritis. Proximal and/or distal realignment of the extensor mechanism
      gives better results than isolated lateral release.

PMID- 18719886
TI  - [Clinical examination for patellofemoral problems].
AB  - Patellofemoral pain and instability account for 25% of all sports-related knee
      problems. However, definitive analysis seems to be difficult. Descriptive
      findings like "anterior knee pain", "patellofemoral pain syndrome", or
      "chondromalacia" are used instead of diagnosis. One reason may be the complex
      pathomechanics of the patellofemoral joint which is suspended between the pelvis,
      the femur, and the tibia and subsequently is influenced by the whole lower
      extremity from the hip down to the foot. On the other hand, different signs and
      functional tests are in use with at times lack of quantification and ambiguous
      interpretation. The current manuscript reviews the commonly used signs and
      functional tests, analyzes them based on the current literature, and arranges
      them in a practical manner for physical examination. A MEDLINE literature search
      and special textbooks regarding patellofemoral disorders were used; 43 signs and
      tests were found. The examiner can quantify 18 of these findings on a nominal and
      15 on an ordinal scale. Thus, this manuscript provides a standardized algorithm
      for physical examination with a collection of quantifiable findings, which are of
      growing importance to justify adequate diagnostics and treatment.

PMID- 18719888
TI  - [Isolated arthrosis of the patellofemoral joint in younger patients (<50 years)].
AB  - In the majority of cases, arthrosis of the patellofemoral joint (PFJ) is combined
      with arthrosis of the femorotibial compartment and thus assumes a somewhat
      secondary role. Nevertheless, it can occur as an isolated entity. Several
      radiological studies evidenced isolated degenerative alterations in the PFJ in
      the age group >55 years (13.6-24.0% in women and 11.0-15.4% in men). In younger
      patients the incidence is lower and is mainly associated with patellar
      instability or post-traumatic arthrosis. Just the same, the choice of appropriate
      treatment for these patients is challenging. Total replacement can be recommended
      for older and less active patients. In contrast, for younger and more active
      patients, various conservative treatment options and more demanding operative
      techniques are available to the surgeon to avoid arthroplasty. This article
      describes the different therapeutic possibilities for managing arthrosis of the
      PFJ in patients aged <50 years.

PMID- 18719889
TI  - [Current treatment for cartilage damage in the patellofemoral joint].
AB  - Joint cartilage damage in adults has practically no tendency to self healing.
      Symptomatic grade III/IV damage requires surgical treatment. There are special
      challenges involved in cartilage damage in the patellofemoral joint as the
      complicated biomechanics of the joint is often combined with dysplasia. All
      tissue regeneration measures are based on the recruitment of cells. The synovial
      cells available in the joint can be differentiated to fibrous cartilage under
      certain mechanical conditions; however, they cannot sufficiently fill in defects.
      Also the use of bone marrow cells for cartilage reconstruction only creates
      mechanically inferior fibrous cartilage (Pridie drillings, microfracture, AMIC).
      Presently only cultivated, autologous chondrocytes from the lab are available for
      a biomechanically high-quality reconstruction of the cartilage layer.The
      application of mesenchymal stem cells is a subject of extensive international
      research. However, the first experimental studies, after initial formation of
      cartilage, disappointingly show significant ossification. Essential conditions
      for a successful treatment of patellofemoral cartilage damage are the diagnosis
      of accompanying pathological conditions, selection of the right cartilage
      regenerating procedure, sufficient removal of the basic pathological defect, and
      implementation of standardized rehabilitation.

PMID- 18719890
TI  - An in vitro analysis of the mechanical properties of 16 arthroscopic knots.
AB  - The purpose of this study was to determine the biomechanical characteristics of
      16 arthroscopic knots and to determine if locking knots have superior loop
      security compared to non-locking knots. Sixteen knot types were tied in
      arthroscopic fashion and tested on a materials testing system. Knots were
      cyclically loaded to 30 Newtons (N) for 20 cycles and then loaded to failure at
      1.25 mm/s. Ten samples of each knot were tied using both #2 Ethibond and #1 PDS
      II. Load to ultimate failure, load to clinical failure, post-cyclic stiffness,
      cyclical elongation, ultimate displacement, loop security, and mode of failure
      were determined for each knot. Nicky's Knot and the French Knot were most
      consistently ranked within the top five knot types for each of the biomechanical
      parameters. Locking knots did not improve loop security over non-locking knots.

PMID- 18719891
TI  - Mutation in the cobO gene generates auxotrophy for cobalamin and methionine and
      impairs the symbiotic properties of Sinorhizobium fredii HH103 with soybean and
      other legumes.
AB  - We report here the isolation of a methionine and cobalamin mutant strain (SVQ336)
      of Sinorhizobium fredii HH103 obtained by Tn5-lacZ mutagenesis. Sequence analysis
      showed that the transposon was inserted into a gene homologous to cobO. This gene
      codes for a cobalamin adenosyltransferase which is involved in the biosynthesis
      of vitamin B12. Another HH103 cobO mutant (strain SVQ524), was constructed by the
      insertion of Omega interposon. Both cobO mutants required the addition of
      methionine because cobalamin acts as a cofactor of the enzyme MetH, which
      catalyses the last step of the methionine biosynthesis. Mutant SVQ524 failed to
      nodulate on Vigna radiate but was able to nodulate on Glycine max cvs. Williams
      and Peking and Cajanus cajan, although the total number of nodules formed was
      highly reduced in comparison with that of plants inoculated with the wild-type
      strain HH103. The roots of these plants did not seem to secrete enough cobalamin
      and/or methionine to support growth of cobalamin/methionine auxotrophs in the
      rhizosphere. In all cases, the phenotype of SVQ524 was nearly overcome by the
      addition of methionine or cobalamin to the plant growth media or by the presence
      of a copy of the cobO gene in cosmid pMUS756.

PMID- 18719892
TI  - Unusual production of glutathione in Actinobacteria.
AB  - Most Actinobacteria produce mycothiol as the major thiol. In addition to
      mycothiol Rhodococcus AD45 generates a substantial level of glutathione possibly
      using genes acquired in a lateral transfer. Instead of mycothiol, Rubrobacter
      radiotolerans and Rubrobacter xylanophilus produce glutathione, whose synthesis
      appears to involve enzymes substantially different from those in other organisms.

PMID- 18719893
TI  - Lower serum cytokine levels in smokers than nonsmokers with chronic schizophrenia
      on long-term treatment with antipsychotics.
AB  - OBJECTIVE: Schizophrenia is associated with various abnormalities in the immune
      system. Suppression of inflammatory cytokines by cigarette smoke is well
      established. The purpose of this study was to determine any differences in
      cytokine profiles in smokers and nonsmokers with schizophrenia and whether there
      were any relationships among altered cytokine profiles and psychopathological
      symptoms. MATERIALS AND METHODS: Serum interleukin (IL)-2, IL-6, IL-8, and tumor
      necrosis factor (TNF)-alpha levels were measured in 96 male inpatients with DSM
      IV schizophrenia: 66 smokers and 30 nonsmokers. Symptoms were assessed with the
      Positive and Negative Syndrome Scale (PANSS). RESULTS: The positive PANSS
      symptoms were lower in smokers than nonsmokers, while the negative symptoms were
      lower in those who smoked more cigarettes. Cytokine levels were positively
      correlated: IL-2 level with IL-6 and IL-6 with both IL-8 and TNF-alpha. Both IL-2
      and IL-6, but not IL-8 or TNF-alpha, were significantly lower in smokers than
      nonsmokers (p < 0.002; p < 0.01). Lower IL-2 levels correlated with fewer
      negative symptoms and with smoking more cigarettes. CONCLUSIONS: The fewer
      positive symptoms in smokers and fewer negative symptoms in those who smoked more
      cigarettes may be associated with nicotine-induced suppression of some
      inflammatory cytokines.

PMID- 18719895
TI  - Detailed structural elucidation of polyesters and acrylates using Fourier
      transform mass spectrometry.
AB  - The detailed structural characterization of complex polymer architectures, like
      copolymers and polymer mixtures, by mass spectrometry presents a challenge. Even
      though soft ionization analyses revolutionized the characterization of large
      molecules and provided a means for determining the polymer's molecular weight
      distribution, polydispersity, and end groups, full microstructure elucidation and
      monomer sequencing by soft ionization alone is not possible. The combination of
      high-resolution Fourier transform mass spectrometry (FTMS) and tandem mass
      spectrometry (MS(n)) provides a powerful analytical tool for addressing these
      challenges. This tool was used in our work to separate and identify the products
      of polymerization between 12-hydroxystearic acid (HSA) and stearic acid (SA), to
      provide precise information about the exact location of caprolactones on the
      Tris(2-hydroxyethyl)isocyanurate (THEIC) molecule, and to sequence a glycidyl
      methacrylate/methyl methacrylate (GMA/MMA) copolymer. The results highlight the
      value of ultrahigh resolution and tandem mass spectrometry for fine structural
      characterization and sequencing of polymers.

PMID- 18719896
TI  - Optimal coherent control of sensitivity and selectivity in spectrochemical
      analysis.
AB  - The number and breadth of coherently controlled chemical processes are escalating
      exponentially since the recent convergence of stable broadband ultrafast laser
      sources, robust pulse shaping devices, and closed-loop optimization routines. We
      show here how these methods can also be applied to spectrochemical analysis. We
      discuss the basics of optimal coherent control and describe their use, both
      present and future, to enhance the sensitivity and/or selectivity of several
      different spectroscopic analytical methods.

PMID- 18719894
TI  - Ameliorating prefrontal cortical dysfunction in mental illness: inhibition of
      phosphotidyl inositol-protein kinase C signaling.
AB  - BACKGROUND: Bipolar disorder and schizophrenia are associated with profound
      dysfunction of the prefrontal cortex (PFC), with bipolar disorder most associated
      with changes in ventromedial PFC and schizophrenia more associated with changes
      in dorsolateral PFC. DISCUSSION: Recent genetic and biochemical studies have also
      linked these illnesses to disinhibition of phosphotidyl inositol-protein kinase C
      signaling. For example, DAG kinase eta, an enzyme that metabolizes DAG and thus
      reduces protein kinase C activity, is the gene most altered in bipolar disorder.
      Similarly, regulator of G protein signaling 4 is the molecule most altered in the
      PFC of patients with schizophrenia, and this molecule normally serves to inhibit
      Gq signaling. Animal studies have shown that high levels of phosphotidyl inositol
      protein kinase C signaling in the PFC markedly impair PFC function at the
      behavioral and cellular levels. Most importantly, many effective medications for
      bipolar disorder and schizophrenia inhibit phosphotidyl inositol-protein kinase C
      signaling, either through intracellular actions (lithium, valproate) or through
      extracellular blockade of receptors coupled to this pathway (5HT2 receptors and
      alpha-1 adrenoceptors). Recent data suggest that lithium and valproate can
      protect gray matter in patients with bipolar disorder. These findings encourage
      the development of protein kinase C inhibitors for the treatment of mental
      illness.

PMID- 18719897
TI  - Transition from monocular motion perception to dichoptic motion perception as a
      function of the stimulus duration.
AB  - We have recently developed a new motion display in which the monocular and
      dichoptic motion components move in opposite directions (Hayashi et al. 2007). In
      the present paper, we estimated the difference between the integration times
      required to detect the dichoptic motion and monocular motion by changing the
      duration of the stimulus. The results showed that monocular motion perception
      becomes more dominant as the stimulus duration becomes shorter, indicating that
      the detection of dichoptic motion is relatively slow process that requires a
      longer integration time compared with the process used to detect monocular
      motion.

PMID- 18719898
TI  - Asymmetric adaptation with functional advantage in human sensorimotor control.
AB  - Human movement control is inherently stochastic, requiring continuous estimation
      of self-motion based upon noisy sensory inputs. The nervous system must determine
      which sensory signals are relevant on a time scale that enables successful
      behavior. In human stance control, failure to effectively adapt to changing
      sensory contexts could lead to injurious falls. Nonlinear changes in postural
      sway amplitude in response to changes in sensory environmental motion have
      indicated a dynamic changing of the weighting of the nervous system's multiple
      sensory inputs so that estimates are based upon the most relevant and accurate
      information available. However, the time scale of these changes is virtually
      unknown. Results here show systematic changes in postural gain when visual scene
      motion amplitude is increased or decreased abruptly, consistent with sensory re
      weighting. However, this re-weighting displayed a temporal asymmetry. When visual
      motion increased, gain decreased within 5 s to a value near its asymptotic value.
      In contrast, when visual motion decreased, it took an additional 5 s for gain to
      increase by a similar absolute amount. Suddenly increasing visual motion
      amplitude threatens balance if gain remains high, and rapid down-weighting of the
      sensory signal is required to avoid falling. By contrast, slow up-weighting
      suggests a conservative CNS strategy. It may not be functional to rapidly up
      weight with transient changes in the sensory environment. Only sustained changes
      necessitate the slower up-weighting process. Such results add to our
      understanding of adaptive processing, identifying a temporal asymmetry in sensory
      re-weighting dynamics that could be a general property of adaptive estimation in
      the nervous system.

PMID- 18719899
TI  - A biomarker for the identification of four Phaeoacremonium species using the beta
      tubulin gene as the target sequence.
AB  - A real-time polymerase chain reaction (PCR) was developed for the rapid detection
      and identification of Phaeoacremonium species, the fungi associated with severe
      diseases in grapevines. A degenerate primer pair (F2bt-R1bt) with homology to the
      beta-tubulin gene was designed to be used in the amplification of 11 species of
      Phaeoacremonium. Four species-specific probes labelled with three different
      fluorescent dyes were designed to be used with the degenerate primers in a real
      time PCR for the identification of Phaeoacremonium aleophilum, P. parasiticum, P.
      viticola and P. mortoniae. Combinations of two probes in a duplex real-time PCR
      allowed to detect and identify a mixture of Phaeoacremonium species and cross
      amplifications were not detected. This method was applied to detect
      Phaeoacremonium species in eight wood fragments from grapevine plants naturally
      infected, and results were compared with those obtained with nested PCR and
      culturing on growth media. Real-time PCR detected Phaeoacremonium in 100% of the
      analysed fragments, whereas nested PCR did only in the 62% of them and requiring
      subsequent restriction fragment-length polymorphism analysis to identify the
      species. This method is a sensitive tool to detect and identify Phaeoacremonium
      species in infected grapevine wood. Real-time PCR assay defined here can be used
      in a plant nursery program to identify pathogen-free plants in order to manage
      Petri disease of grapevines.

PMID- 18719900
TI  - Directed evolution of a Baeyer-Villiger monooxygenase to enhance
      enantioselectivity.
AB  - The Baeyer-Villiger monooxygenase (BVMO) BmoF1 from Pseudomonas fluorescens DSM
      50106 was shown before to enantioselectively oxidize different 4-hydroxy-2
      ketones to the corresponding hydroxyalkyl acetates, being the first example of a
      BVMO-catalyzed kinetic resolution of aliphatic acyclic ketones. However, the wild
      type enzyme exhibited only moderate E values (E approximately 55). Thus, the
      enantioselectivity was enhanced by means of directed evolution and optimization
      of reaction conditions since it was found that higher E values (E approximately
      70 for wild-type BmoF1) could already be obtained when performing
      biotransformations in shake flasks rather than small tubes. In a first step,
      random mutations were introduced by error-prone polymerase chain reaction, and
      BmoF1 mutants (>3,500 clones) were screened for improved activity and
      enantioselectivity using a microtiter-plate-based screening method. Mutations
      S136L and L252Q were found to increase conversion compared to wild type, while
      several mutations (H51L, F225Y, S305C, and E308V) were identified enhancing the
      enantioselectivity to a varying extent (E approximately 75-90). In a second step,
      beneficial mutations were recombined by consecutive cycles of QuikChange site
      directed mutagenesis resulting in a double mutant (H51L/S136L) showing both
      improved conversion and enantioselectivity (E approximately 86).

PMID- 18719901
TI  - Microencapsulated bile salt hydrolase producing Lactobacillus reuteri for oral
      targeted delivery in the gastrointestinal tract.
AB  - This is the first study of its kind to screen probiotic lactic acid bacteria for
      the purpose of microencapsulating a highly bile salt hydrolase (BSH)-active
      strain. A Lactobacillus reuteri strain and a Bifidobacterium longum strain were
      isolated as the highest BSH producers among the candidates. Microcapsules were
      prepared with a diameter of 619 +/- 31 mum and a cell load of 5 x 10(9) cfu/ml.
      Post de Man, Rogosa, and Sharpe broth-acid challenge, L. reuteri microcapsules
      metabolized glyco- and tauro-conjugated bile salts at rates of 10.16 +/- 0.46 and
      1.85 +/- 0.33 micromol/g microcapsule per hour, respectively, over the first 2 h.
      Microencapsulated B. longum had minimal BSH activity and were significantly (P <
      0.05) more susceptible to acid challenge. Further testing of L. reuteri
      microcapsules in a simulated human gastrointestinal (GI) model showed an improved
      rate, with 49.4 +/- 6.21% of glyco-conjugates depleted after 60 min and complete
      deconjugation after 4 h. Microcapsules protected the encased cells in the
      simulated stomach maintaining L. reuteri viability above 10(9), 10(8), and 10(6)
      cfu/ml after 2 h at pH 3.0, 2.5, and 2.0, respectively. Results show excellent
      potential for this highly BSH-active microencapsulation system in vitro,
      highlighted by improved viability and substrate utilization in simulated GI
      transit.

PMID- 18719902
TI  - The GC and window-averaged DNA curvature profile of secondary metabolite gene
      cluster in Aspergillus fumigatus genome.
AB  - An immense variety of complex secondary metabolites is produced by filamentous
      fungi including Aspergillus fumigatus, a main inducer of invasive aspergillosis.
      The identification of fungal secondary metabolite gene cluster is essential for
      the characterization of fungal secondary metabolism in terms of genetics and
      biochemistry through recombinant technologies such as gene disruption and
      cloning. Most of the prediction methods for secondary metabolite gene cluster
      severely depend on homology searches. However, homology-based approach has
      intrinsic limitation to unknown or novel gene cluster. We analyzed the GC and
      window-averaged DNA curvature profile of 26 secondary metabolite gene clusters in
      the A. fumigatus genome to find out potential conserved features of secondary
      metabolite gene cluster. Fifteen secondary metabolite gene clusters showed a
      conserved pattern in window-averaged DNA curvature profile, that is, the DNA
      regions including secondary metabolic signature genes such as polyketide
      synthase, nonribosomal peptide synthase, and/or dimethylallyl tryptophan synthase
      consisted of window-averaged DNA curvature values lower than 0.18 and these DNA
      regions were at least 20 kb. Forty percent of secondary metabolite gene clusters
      with this conserved pattern were related to severe regulation by a transcription
      factor, LaeA. Our result could be used for identification of other fungal
      secondary metabolite gene clusters, especially for secondary metabolite gene
      cluster that is severely regulated by LaeA or other proteins with similar
      function to LaeA.

PMID- 18719903
TI  - Cloning and enzymatic characterization of a xylanase gene from a soil-derived
      metagenomic library with an efficient approach.
AB  - Screening interesting biocatalysts directly from soil samples is a more
      convenient and applicable approach than conventional cultivation-dependent ones.
      In our present work, a soil-derived metagenomic library containing 24,000
      transformants was constructed with an efficient strategy for cloning xylanase
      genes. A gene encoding the enzyme (XynH) able to hydrolyze xylan was obtained.
      Similarity analysis revealed that this enzyme is a new member in the family 10 of
      xylanases. The molecular mass of XynH purified from Escherichia coli was
      estimated to be 39 kDa by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis analysis. It was found to display the maximal activity at lower
      temperature, under weakly alkaline conditions, different from most of xylanases.
      The K(m) and V(max) values of XynH with birchwood xylan as substrate are 7.5
      mg/ml and 190 micromol min(-1 )mg(-1), respectively. It is greatly interesting to
      note that the activity of XynH was not reduced significantly by Mn(2+), Zn(2+),
      Co(2+), Ag(+), and Cu(2+), even at the concentration of 5 mM, which strongly
      inhibits most of the other xylanases studied previously.

PMID- 18719904
TI  - Involvement of PEG-carboxylate dehydrogenase and glutathione S-transferase in PEG
      metabolism by Sphingopyxis macrogoltabida strain 103.
AB  - Sphingopyxis terrae and the Sphingopyxis macrogoltabida strains 103 and 203 are
      able to degrade polyethylene glycol (PEG). They possess the peg operon, which is
      responsible for the conversion of PEG to PEG-carboxylate-coenzyme A (CoA). The
      upstream (3.0 kb) and downstream (6.5 kb) regions of the operon in strain 103
      were cloned and sequenced. The structure was well conserved between S.
      macrogoltabida strain 203 and S. terrae, except that two sets of transposases are
      absent in strain 203. The downstream region contains the genes for PEG
      carboxylate dehydrogenase (PCDH), glutathione S-transferase (GST), tautomerase,
      and a hypothetical protein. The genes for pcdh and gst were transcribed
      constitutively and monocistronically, indicating that their transcription is
      independent of the operon regulation. PCDH and GST were expressed in Escherichia
      coli and characterized biochemically. PCDH is a homotetramer of 64-kDa subunits
      and contains one molecule of flavin adenine dinucleotide per subunit. The enzyme
      dehydrogenates PEG-carboxylate to yield glyoxylate, suggesting that the enzyme is
      the third enzyme involved in PEG degradation. GST is a homodimer of 28-kDa
      subunits. GST activity was noncompetitively inhibited by acyl-CoA and PEG
      carboxylate-CoA, suggesting the interaction of GST with them. The proposed role
      for GST is to buffer the toxicity of PEG-carboxylate-CoA.

PMID- 18719905
TI  - Thermotoga maritima TM0298 is a highly thermostable mannitol dehydrogenase.
AB  - Thermotoga maritima TM0298 is annotated as an alcohol dehydrogenase, yet it shows
      high identity and similarity to mesophilic mannitol dehydrogenases. To
      investigate this enzyme further, its gene was cloned and expressed in Escherichia
      coli. The purified recombinant enzyme was most active on fructose and mannitol,
      making it the first known hyperthermophilic mannitol dehydrogenase. T. maritima
      mannitol dehydrogenase (TmMtDH) is optimally active between 90 and 100 degrees C
      and retains 63% of its activity at 120 degrees C but shows no detectable activity
      at room temperature. Its kinetic inactivation follows a first-order mechanism,
      with half-lives of 57 min at 80 degrees C and 6 min at 95 degrees C. Although
      TmMtDH has a higher V (max) with NADPH than with NADH, its catalytic efficiency
      is 2.2 times higher with NADH than with NADPH and 33 times higher with NAD(+)
      than with NADP(+). This cofactor specificity can be explained by the high density
      of negatively charged residues (Glu193, Asp195, and Glu196) downstream of the
      NAD(P) interaction site, the glycine motif. We demonstrate that TmMtDH contains a
      single catalytic zinc per subunit. Finally, we provide the first proof of concept
      that mannitol can be produced directly from glucose in a two-step enzymatic
      process, using a Thermotoga neapolitana xylose isomerase mutant and TmMtDH at 60
      degrees C.

PMID- 18719906
TI  - Reduced striatal D2 receptor binding in myoclonus-dystonia.
AB  - PURPOSE: To study striatal dopamine D(2) receptor availability in DYT11 mutation
      carriers of the autosomal dominantly inherited disorder myoclonus-dystonia (M-D).
      METHODS: Fifteen DYT11 mutation carriers (11 clinically affected) and 15 age- and
      sex-matched controls were studied using (123)I-IBZM SPECT. Specific striatal
      binding ratios were calculated using standard templates for striatum and
      occipital areas. RESULTS: Multivariate analysis with corrections for ageing and
      smoking showed significantly lower specific striatal to occipital IBZM uptake
      ratios (SORs) both in the left and right striatum in clinically affected patients
      and also in all DYT11 mutation carriers compared to control subjects.
      CONCLUSIONS: Our findings are consistent with the theory of reduced dopamine D(2)
      receptor (D2R) availability in dystonia, although the possibility of increased
      endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled
      out.

PMID- 18719907
TI  - Recombinant carcinoembryonic antigen as a reporter gene for molecular imaging.
AB  - PURPOSE: Reporter genes can provide a way of noninvasively assessing gene
      activity in vivo. However, current reporter gene strategies may be limited by the
      immunogenicity of foreign reporter proteins, endogenous expression, or unwanted
      biological activity. We have developed a reporter gene based on carcinoembryonic
      antigen (CEA), a human protein with limited normal tissue expression. METHODS: To
      construct a CEA reporter gene for PET, a CEA minigene (N-A3) was fused to the
      extracellular and transmembrane domains of the human Fc gamma RIIb receptor. The
      NA3-Fc gamma RIIb recombinant gene, driven by a CMV promoter, was transfected in
      Jurkat (human T cell leukemia) cells. Expression was analyzed by flow cytometry,
      immunohistochemistry (IHC), and microPET imaging. RESULTS: Flow cytometry
      identified Jurkat clones stably expressing NA3-Fc gamma RIIb at low, medium, and
      high levels. High and medium NA3-Fc gamma RIIb expression could also be detected
      by Western blot. Reporter gene positive and negative Jurkat cells were used to
      establish xenografts in athymic mice. IHC showed staining of the tumor with high
      reporter gene expression; medium and low N-A3 expression was not detected.
      MicroPET imaging, using an anti-CEA (124)I-labeled single-chain Fv-Fc antibody
      fragment, demonstrated that only high N-A3 expression could be detected. Specific
      accumulation of activity was visualized at the N-A3 positive tumor as early as 4
      h. MicroPET image quantitation showed tumor activity of 1.8 +/- 0.2, 15.2 +/-
      1.3, and 4.6 +/- 1.2 percent injected dose per gram (%ID/g) at 4, 20, and 48 h,
      respectively. Biodistribution at 48 h demonstrated tumor uptake of 4.8 +/-
      0.8%ID/g. CONCLUSION: The CEA N-A3 minigene has the potential to be used as a
      reporter gene for imaging cells in vivo.

PMID- 18719908
TI  - Infarct size in primary angioplasty without on-site cardiac surgical backup
      versus transferal to a tertiary center: a single photon emission computed
      tomography study.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PCI) performed in large
      community hospitals without cardiac surgery back-up facilities (off-site) reduces
      door-to-balloon time compared with emergency transferal to tertiary
      interventional centers (on-site). The present study was performed to explore
      whether off-site PCI for acute myocardial infarction results in reduced infarct
      size. METHODS AND RESULTS: One hundred twenty-eight patients with acute ST
      segment elevation myocardial infarction were randomly assigned to undergo primary
      PCI at the off-site center (n = 68) or to transferal to an on-site center (n =
      60). Three days after PCI, (99m)Tc-sestamibi SPECT was performed to estimate
      infarct size. Off-site PCI significantly reduced door-to-balloon time compared
      with on-site PCI (94 +/- 54 versus 125 +/- 59 min, respectively, p < 0.01),
      although symptoms-to-treatment time was only insignificantly reduced (257 +/- 211
      versus 286 +/- 146 min, respectively, p = 0.39). Infarct size was comparable
      between treatment centers (16 +/- 15 versus 14 +/- 12%, respectively p = 0.35).
      Multivariate analysis revealed that TIMI 0/1 flow grade at initial coronary
      angiography (OR 3.125, 95% CI 1.17-8.33, p = 0.023), anterior wall localization
      of the myocardial infarction (OR 3.44, 95% CI 1.38-8.55, p < 0.01), and
      development of pathological Q-waves (OR 5.07, 95% CI 2.10-12.25, p < 0.01) were
      independent predictors of an infarct size > 12%. CONCLUSIONS: Off-site PCI
      reduces door-to-balloon time compared with transferal to a remote on-site
      interventional center but does not reduce infarct size. Instead, pre-PCI TIMI 0/1
      flow, anterior wall infarct localization, and development of Q-waves are more
      important predictors of infarct size.

PMID- 18719911
TI  - Abstracts of the Annual Congress of the European Association of Nuclear Medicine
      (EANM). October 12-15, 2008. Munich, Germany.

PMID- 18719909
TI  - Diagnostic value of PET/CT for the staging and restaging of pediatric tumors.
AB  - OBJECTIVE: The objective of this retrospective study was to compare the
      diagnostic value of 2-[(18)F]fluoro-2-deoxy-D: -glucose positron emission
      tomography ((18)F-FDG PET)/CT versus (18)F-FDG PET and CT alone for staging and
      restaging of pediatric solid tumors. METHODS: Forty-three children and
      adolescents (19 females and 24 males; mean age, 15.2 years; age range, 6-20
      years) with osteosarcoma (n = 1), squamous cell carcinoma (n = 1), synovial
      sarcoma (n = 2), germ cell tumor (n = 2), neuroblastoma (n = 2), desmoid tumor (n
      = 2), melanoma (n = 3), rhabdomyosarcoma (n = 5), Hodgkin's lymphoma (n = 7), non
      Hodgkin-lymphoma (n = 9), and Ewing's sarcoma (n = 9) who had undergone (18)F-FDG
      PET/CT imaging for primary staging or follow-up of metastases were included in
      this study. The presence, location, and size of primary tumors was determined
      separately for PET/CT, PET, and CT by two experienced reviewers. The diagnosis of
      the primary tumor was confirmed by histopathology. The presence or absence of
      metastases was confirmed by histopathology (n = 62) or clinical and imaging
      follow-up (n = 238). RESULTS: The sensitivities for the detection of solid
      primary tumors using integrated (18)F-FDG PET/CT (95%), (18)F-FDG PET alone
      (73%), and CT alone (93%) were not significantly different (p > 0.05). Seventeen
      patients showed a total of 153 distant metastases. Integrated PET/CT had a
      significantly higher sensitivity for the detection of these metastases (91%) than
      PET alone (37%; p < 0.05), but not CT alone (83%; p > 0.05). When lesions with a
      diameter of less than 0.5 cm were excluded, PET/CT (89%) showed a significantly
      higher specificity compared to PET (45%; p < 0.05) and CT (55%; p < 0.05). In a
      sub-analysis of pulmonary metastases, the values for sensitivity and specificity
      were 90%, 14%, 82% and 63%, 78%, 65%, respectively, for integrated PET/CT, stand
      alone PET, and stand-alone CT. For the detection of regional lymph node
      metastases, (18)F-FDG PET/CT, (18)F-FDG PET alone, and CT alone were
      diagnostically correct in 83%, 61%, and 42%. A sub-analysis focusing on the
      ability of PET/CT, PET, and CT to detect osseous metastases showed no
      statistically significant difference between the three imaging modalities (p >
      0.05). CONCLUSION: Our study showed a significantly increased sensitivity of
      PET/CT over that of PET for the detection of distant metastases but not over that
      of CT alone. However, the specificity of PET/CT for the characterization of
      pulmonary metastases with a diameter > 0.5 cm and lymph node metastases with a
      diameter of <1 cm was significantly increased over that of CT alone.

PMID- 18719912
TI  - The new EANM paediatric dosage card.

PMID- 18719913
TI  - Immune stimulatory antigen loaded particles combined with depletion of regulatory
      T-cells induce potent tumor specific immunity in a mouse model of melanoma.
AB  - Anti-tumor vaccines capable of activating both CD4 and CD8 T cells are preferred
      for long lasting T cell responses. Induction of a tumor-specific T-cell response
      can be induced by tumor vaccines that target innate immunity. The ensuing T-cell
      response depends on efficient antigen presentation from phagocytosed cargo in the
      antigen presenting cell and is augmented by the presence of Toll-like receptor
      (TLR) ligands within the cargo. Biodegradable polymers are useful for vaccine
      delivery in that they are phagocytosed by antigen presenting cells (APCs) and
      could potentially be loaded with both the antigen and immune stimulatory TLR
      agents. This study was undertaken to evaluate the effect of poly lactic-co
      glycolic acid (PLGA) polymer particles loaded with antigenic tumor lysate and
      immune stimulatory CpG oligonucleotides on induction of tumor specific immunity
      in a mouse model of melanoma. We found that after delivery, these immune
      stimulatory antigen loaded particles (ISAPs) efficiently activated APCs and were
      incorporated into lysosomal compartments of macrophages and dendritic cells. ISAP
      vaccination resulted in remarkable T cell proliferation, but only modestly
      suppressed tumor growth of established melanoma. Due to this discordant effect on
      tumor immunity we evaluated the role of regulatory T cells (Treg) and found that
      ISAP vaccination or tumor growth alone induced prolific expansion of tumor
      specific Treg. When the Treg compartment was suppressed with anti-CD25 antibody,
      ISAP vaccination induced complete antigen-specific immunity in a prophylactic
      model. ISAP vaccination is a novel tumor vaccine strategy that is designed to co
      load the antigen with a TLR agonist enabling efficient Ag presentation. Targeting
      of T-reg expansion during vaccination may be necessary for inducing effective
      tumor-specific immunity.

PMID- 18719914
TI  - Aberrant expression of the hematopoietic-restricted minor histocompatibility
      antigen LRH-1 on solid tumors results in efficient cytotoxic T cell-mediated
      lysis.
AB  - CD8(+) T cells recognizing minor histocompatibility antigens (MiHA) on solid
      tumor cells may mediate effective graft-versus-tumor (GVT) reactivity after
      allogeneic stem cell transplantation (SCT). Previously, we identified LRH-1 as a
      hematopoietic-restricted MiHA encoded by the P2X5 gene. Here, we report that LRH
      1 is aberrantly expressed on solid tumor cells. P2X5 mRNA expression is
      demonstrated in a significant portion of solid tumor cell lines, including renal
      cell carcinoma (RCC), melanoma, colorectal carcinoma, brain cancer and breast
      cancer. Importantly, P2X5 gene expression was also detected in a subset of
      primary solid tumor specimens derived from RCC, brain cancer and breast cancer
      patients. Furthermore, P2X5 expressing solid tumor cells can be effectively
      targeted by LRH-1-specific cytotoxic T lymphocytes under inflammatory conditions.
      The expression of HLA-B7 and CD54 on tumor cells increases upon cytokine
      stimulation resulting in improved T cell activation as observed by higher levels
      of degranulation and enhanced tumor cell lysis. Overall, hematopoietic-restricted
      MiHA LRH-1 is aberrantly expressed on solid tumor cells and may be used as target
      in GVT-specific immunotherapy after SCT.

PMID- 18719915
TI  - Review of clinical studies on dendritic cell-based vaccination of patients with
      malignant melanoma: assessment of correlation between clinical response and
      vaccine parameters.
AB  - During the past years numerous clinical trials have been carried out to assess
      the ability of dendritic cell (DC) based immunotherapy to induce clinically
      relevant immune responses in patients with malignant diseases. A broad range of
      cancer types have been targeted including malignant melanoma which in the
      disseminated stage have a very poor prognosis and only limited treatment options
      with moderate effectiveness. Herein we describe the results of a focused search
      of recently published clinical studies on dendritic cell vaccination in melanoma
      and review different vaccine parameters which are frequently claimed to have a
      possible influence on clinical response. These parameters include performance
      status, type of antigen, DC maturation status, route of vaccine administration,
      use of adjuvant, and vaccine induced immune response. In total, 38 articles found
      through Medline search, have been included for analysis covering a total of 626
      patients with malignant melanoma treated with DC based therapy. Clinical response
      (CR, PR and SD) were found to be significantly correlated with the use of peptide
      antigens (p = 0.03), the use of any helper antigen/adjuvant (p = 0.002), and
      induction of antigen specific T cells (p = 0.0004). No significant correlations
      between objective response (CR and PR) and the tested parameters were found.
      However, a few non-significant trends were demonstrated; these included an
      association between objective response and use of immature DCs (p = 0.08), use of
      adjuvant (p = 0.09), and use of autologous antigen preparation (p = 0.12). The
      categorisation of SD in the response group is debatable. Nevertheless, when the
      SD group were analysed separately we found that SD was significantly associated
      with use of peptide antigens (p = 0.0004), use of adjuvant (p = 0.01), and
      induction of antigen specific T cells (p = 0.0003). No specific route of vaccine
      administration showed superiority. Important lessons can be learned from previous
      studies, interpretation of these findings should, however, be done with
      reservation for the many minor deviations in the different treatment schedules
      among the published studies, which were not considered in order to be able to
      process and group the data.

PMID- 18719916
TI  - Factors predicting the failure of Bernese periacetabular osteotomy: a meta
      regression analysis.
AB  - There is no clear evidence regarding the outcome of Bernese periacetabular
      osteotomy (PAO) in different patient populations. We performed systematic meta
      regression analysis of 23 eligible studies. There were 1,113 patients of which 61
      patients had total hip arthroplasty (THA) (endpoint) as a result of failed
      Bernese PAO. Univariate analysis revealed significant correlation between THA and
      presence of grade 2/grade 3 arthritis, Merle de'Aubigne score (MDS), Harris hip
      score and Tonnis angle, change in lateral centre edge (LCE) angle, late proximal
      femoral osteotomies, and heterotrophic ossification (HO) resection. Multivariate
      analysis showed that the odds of having THA increases with grade 2/grade 3
      osteoarthritis (3.36 times), joint penetration (3.12 times), low preoperative MDS
      (1.59 times), late PFO (1.59 times), presence of preoperative subluxation (1.22
      times), previous hip operations (1.14 times), and concomitant PFO (1.09 times).
      In the absence of randomised controlled studies, the findings of this analysis
      can help the surgeon to make treatment decisions.

PMID- 18719917
TI  - Tri-lineage disease involving sideroblastic anaemia, multiple myeloma and B-cell
      non-Hodgkin's lymphoma in the same patient.

PMID- 18719918
TI  - Hyperhomocysteinemia in ankylosing spondylitis: prevalence and association with
      clinical variables.
AB  - We evaluated the prevalence and characteristics associated with
      hyperhomocysteinemia in ankylosing spondylitis (AS). Ninety-seven patients with
      AS were compared with 97 controls. The assessment included clinical
      characteristics, disease activity (BASDAI), functioning (BASFI), history of
      drugs, and erythrocyte sedimentation rate (ESR). Total serum homocysteine (tHcy)
      was determined by fluorescence polarization immunoassay. A higher frequency of
      hyperhomocysteinemia (>15 micromol/L) was observed in AS (12 vs. 1%, P = 0.002).
      In the multivariate analysis the risk for hyperhomocysteinemia was increased in
      patients with higher score of HAQ-S (OR = 5.27, 95% CI: 1.29-21.44) and higher
      ESR (OR = 1.09, 95% CI: 1.02-1.18). No statistical associations was observed
      between hyperhomocysteinemia with other variables including methotrexate or
      sulfasalazine utilization. In conclusion, this study found a significant
      prevalence of hyperhomocysteinemia in Mexican patients with AS mainly associated
      to a worst functional impairment. Further follow-up studies are required to
      evaluate the risk of cardiovascular disease in these patients.

PMID- 18719919
TI  - A case of limited systemic sclerosis with p-ANCA, complicated by multiple
      cerebral hemorrhages.
AB  - ANCA associated vasculitides are a group of disorders characterized by the
      presence of necrotizing inflammation of blood vessels that involve venules,
      capillaries, arterioles, arteries, and veins. They are characterized by the
      presence of antineutrophil cytoplasmic antibodies (ANCA). ANCA associated
      vasculitis commonly affects the kidney producing proteinuria, hematuria and
      variable degrees of renal failure. Other organs involved include the lung, skin
      and peripheral nervous system. We present a patient with limited systemic
      sclerosis, who later developed pauci-immune glomerulonephritis with p-ANCA
      (antimyeloperoxidase) specificity and, whose disease was later complicated by
      cerebral vasculitis with multiple intracerebral hemorrhages.

PMID- 18719920
TI  - Higher LPS-stimulated TNF-alpha mRNA levels in peripheral blood mononuclear cells
      from Chinese ankylosing spondylitis patients with -308G/A polymorphism in
      promoter region of tumor necrosis factor: association with distinct A33/B58/Cw10
      haplotypes.
AB  - To investigate the effects of TNF-alpha -308, -238 promoter polymorphisms on TNF
      alpha transcription in B27 positive Chinese patients with ankylosing spondylitis
      (AS). The possible relationship between polymorphisms, MHC antigens, and
      quantitative TNF-alpha mRNA expression were evaluated. Single nucleotide
      polymorphisms (SNPS) of TNF-alpha -308 and -238 were performed by PCR
      amplification refractory mutation system method (PCR-ARMS) in sixty-seven B27
      positive AS patients and 60 HLA-B27 positive healthy controls in Chinese.
      Quantitative measurement of TNF-alpha mRNA in peripheral blood mononuclear cells
      was performed with real time RT-PCR. The polymorphisms were correlated to
      quantitative TNF-alpha mRNA, and MHC antigens (determined by SSP method) in AS
      patients. The prevalence rate of both -308G/A and -238G/A TNF-alpha promoter
      polymorphisms in patients were not significantly different from those in normal
      subjects. However, a significant high LPS-stimulated TNF-alpha mRNA expression
      was found in peripheral blood mononuclear cells from patients with promoter 
      308G/A polymorphism (TNF2) as compared to those in -308G/G genotype (TNF1).
      Furthermore, -308G/A polymorphism in patients was found to be tightly associated
      with distinct haplotypes of A33/B58/Cw10 [12 out of 14 -308G/A patients (85.7%)
      versus none in 53 -308G/G patients], independent of B27 antigen. HLA-A33-B58-Cw10
      haplotypes associated TNF-alpha promoter -308G/A polymorphism might play an
      important role in disease pathogenesis of AS in Chinese population, partially
      related to a driving force of a higher TNF-alpha production. It confirms once
      again the importance and complexity of MHC related molecules in disease
      pathogenesis of AS.

PMID- 18719921
TI  - [Strabismus correction as an alternative treatment to evisceration and
      enucleation for artificial eye prosthesis intolerance in atrophic eyes].
AB  - We report on two patients, each with an atrophic blind eye who underwent
      strabismus correction as an alternative treatment of artificial eye prosthesis
      intolerance. Both patients had acquired intolerance of their prostheses, which
      could not be adjusted by the ocularist. The intolerance was assumed to result
      from focal corneal pressure by the prosthesis, related to progressive exotropia
      and hypertropia. This led to irritation and pain in both patients, and to focal
      corneal staining in one. Both patients underwent retropositioning of the external
      and superior rectus muscles of the left eye. At 4 weeks and 13 months
      postoperatively, they were free of symptoms while wearing the original artificial
      eye prosthesis.

PMID- 18719922
TI  - Characteristic differences in modulation of stomatogastric musculature by a
      neuropeptide in three species of Cancer crabs.
AB  - Stomatogastric musculature from crabs in the genus Cancer provides a system in
      which modulatory roles of peptides from the FLRFamide family can be compared. The
      anterior cardiac plexus (ACP) is a neuroendocrine release site within the Cancer
      stomatogastric nervous system that is structurally identical in C. borealis, C.
      productus, and C. magister but that appears to contain FLRFamide-like peptide(s)
      only in C. productus. We measured the effect of TNRNFLRFamide on nerve-evoked
      contractions of muscles that were nearby, an intermediate distance, or far from
      the ACP. We found the spatial pattern of FLRFamidergic modulation of muscles in
      C. productus to be qualitatively different than in C. borealis or C. magister. In
      C. productus, muscles proximal to the ACP were more responsive than distal
      muscles. In C. borealis, FLRFamidergic response was less dependent on muscle
      location. These results suggest that functionally different roles of FLRFamides
      in modulating stomatogastric muscle movements may have evolved in different
      Cancer species.

PMID- 18719925
TI  - Cushing's syndrome due to unilateral multiple adrenal adenomas as an
      extraintestinal manifestation of familial adenomatous polyposis.

PMID- 18719924
TI  - Comparative study between biofeedback retraining and botulinum neurotoxin in the
      treatment of anismus patients.
AB  - PURPOSE: Anismus is a significant cause of chronic constipation. This study came
      to revive the results of BFB training and BTX-A injection in the treatment of
      anismus patients. MATERIALS AND METHODS: Forty-eight patients with anismus (33
      women; mean age 39.6 +/- 15.9) were included in this study. All patients
      fulfilled Rome II criteria for functional constipation. All patients underwent
      anorectal manometry, balloon expulsion test, defecography, and electromyography
      (EMG) activity of the EAS. All patients had non-relaxing puborectalis muscle. The
      patients were randomized into two groups. Group I patients received biofeedback
      therapy, two times per week for about 1 month. Group II patients were injected
      with BTX-A. Follow-up was conducted weekly in the first month then monthly for
      about 1 year. RESULTS: In the BFB training group, three patients quit before the
      end of sessions with no improvement; initial improvement was recorded in 12
      patients (50%) while long-term success was recorded in six patients (25%). In the
      BTX-A group, clinical improvement was recorded in 17 patients (70.83%), but the
      improvement persisted only in eight patients (33.3%). There is a significant
      difference between BTX-A group and BFB group regarding the initial success, but
      this significant difference disappeared at the end of follow-up. Manometric
      relaxation was achieved significantly post-BFB and post-BTX-A injection with no
      significant difference between the two groups. CONCLUSIONS: Biofeedback training
      has a limited therapeutic effect on patients suffering from anismus. BTX-A
      injection seems to be successful for temporary treatment of anismus.

PMID- 18719926
TI  - [Recommedations for the use of abatacept in patients with rheumatoid arthritis].

PMID- 18719927
TI  - Redislocation after treatment of traumatic dislocation of hip in children: a
      report of two cases and literature review.
AB  - From August 1998 to June 2005, we treated five children (age range 2-9 years)
      with traumatic dislocation of hip. The mean follow-up period was 4.1 years (range
      1-8 years). There was acceptable reduction in all cases by single attempt at
      closed reduction. Two patients aged 2 and 3 years, respectively, had
      redislocation. Other complications like nerve injuries, avascular necrosis,
      growth disturbance, ectopic ossification and post-traumatic arthritis were not
      seen till the last follow-up (mean 4.1; range 1-8 years). Closed reduction is an
      effective treatment method for traumatic dislocation of hip in children, but
      adequate immobilization and protection from weight bearing is needed in children
      aged less than 10 years to prevent redislocation.

PMID- 18719928
TI  - Outcome of stemmed shoulder hemi-arthroplasty revision.
AB  - INTRODUCTION: We report our experience of revision of failed stemmed shoulder
      hemi-arthroplasty for causes other than infection. MATERIAL/METHOD: Seventeen
      revisions were followed for a minimum of 2 years. Fifteen cases were revised for
      symptomatic glenoid erosion. Sixteen were revised to a total shoulder
      arthroplasty and one to a cuff tear arthropathy head. RESULT: The mean visual
      analogue pain score following revision surgery was reduced from 6.7 to 3.2 (P =
      0.008). However the Constant-Murley and the Association of Shoulder and Elbow
      Surgeons scores failed to improve significantly. CONCLUSION: We conclude that
      revision surgery for failed stemmed shoulder hemi-arthroplasty improves pain but
      not function.

PMID- 18719929
TI  - An unusual case of gonococcal arthritis of the finger.
AB  - Gonococcal arthritis is the most common acute septic arthritis in sexually active
      young adults. It is caused by the gram-negative diplococcus Neisseria
      gonorrhoeae. In 0.5-3% an untreated mucosal infection disseminates throughout the
      system and affects mostly big joints like the knee, elbows, and ankles. N.
      gonorrhoeae is a fragile microorganism which is difficult to culture. Penicillin
      resistance has developed worldwide in recent years, therefore, patients should be
      treated by a third generation Cephalosporin. In this article, we describe the
      unexpected finding of septic arthritis in the proximal interphalangeal joint of a
      50-year-old patient. The septic arthritis was caused by N. gonorrhoeae.

PMID- 18719930
TI  - Sublaminar wiring stabilization to prevent adjacent segment degeneration after
      lumbar spinal fusion.
AB  - INTRODUCTION: Adjacent segment degeneration (ASD) is a complication of lumbar
      spinal fusion. There are some reports on the cause of this degeneration but none
      concerning its prevention. We performed sublaminar wiring stabilization to
      prevent ASD after posterolateral lumbar spinal fusion with instrumentation. The
      purpose of this study was to prospectively evaluate the efficacy of this
      procedure. PATIENTS AND METHODS: Between 2003 and 2004, 54 consecutive patients
      with lumbar spinal canal stenosis and multilevel instability of the lumbar spine
      underwent posterior decompression and posterolateral fusion with instrumentation.
      The mean age at the time of surgery was 66.7 +/- 1.3 years, and the mean follow
      up period was 40.0 +/- 1.1 months, with a minimum of 29 months. Twenty-seven of
      the patients underwent conventional sublaminar wiring stabilization at the
      cephalad segment adjacent to the site of fusion to prevent ASD (group A), and the
      other 27 patients did not (group B). Some items were assessed, including clinical
      outcome using Japanese Orthopaedic Association (JOA) score, sagittal global
      lumbar alignment, and segmental motion in flexion-extension radiographs of the
      cephalad vertebral body adjacent to the site of fusion. RESULTS: There were no
      significant differences in JOA scores between two groups, but 2 patients in group
      B underwent subsequent surgery due to ASD. Sagittal lumbar alignment did not
      change in group A but was significantly decreased in group B. With respect to
      segmental motion in flexion-extension radiographs, group A showed a significant
      decrease from 6.9 degrees before surgery to 3.4 degrees after surgery, on the
      other hand group B showed a significant increase from 5.6 degrees before surgery
      to 8.4 degrees after surgery. CONCLUSIONS: In this study, it was suggested that
      sublaminar wiring stabilization significantly reduces the range of motion of the
      adjacent segment and preserves sagittal lumbar alignment, which lead to
      prevention of ASD. The clinical outcome of the subsequent surgeries is relatively
      poor, so it is important to prevent ASD by any prevention such as sublaminar
      wiring stabilization.

PMID- 18719931
TI  - Quantification of acromioclavicular reduction parameters after the Weaver-Dunn
      procedure.
AB  - BACKGROUND: The combination of the reconstruction of the coracoclavicular
      ligaments with the resection arthroplasty of the distal end of the clavicle is a
      commonly used technique in acromioclavicular separations. HYPOTHESIS: The purpose
      of the current study was to quantify the reduction parameters using 3-D CT and to
      analyze their effects on clinical outcomes. STUDY DESIGN: Case series. METHODS:
      The patients with chronic symptoms after acromioclavicular dislocation (type III)
      were treated with reconstruction of the coracoclavicular ligaments. The average
      follow-up was 69.5 months. The patient group consisted of 21 men and 8 women. The
      initial treatment at the time of injury was nonoperative in 26 of 29 patients. CT
      was used to document anteroposterior (APD), craniocaudal (CCD) and mediolateral
      (MLD) acromioclavicular reduction parameters. Constant Shoulder scoring system
      was used. RESULTS: The mean preoperative Constant score was 56.62 +/- 18.63
      points while the postoperative score was 89.93 +/- 10.79 points. The mean APD was
      9.2 mm, the mean CCD was 1.1 mm and the mean MLD was 8.4 mm. There was no
      correlation between the APD, MLD and the Constant Scores. However, an inverse
      correlation between the CCD and the postoperative Constant Scores was found.
      CONCLUSIONS: CCD plays an important role on the postoperative function. If the
      CCD is larger, the Constant score is lower. CLINICAL RELEVANCE: The reduction
      loss is a distinctive parameter of the functional outcome, even when the
      reconstructed coracoclavicular ligament is intact. Secure fixation may be
      achieved with techniques preserving CCD.

PMID- 18719932
TI  - Is there a role for mast cells in psoriasis?
AB  - Mast cells have traditionally been considered as effector cells in allergy but
      during the last decade it has been realized that mast cells are essentially
      involved in the mechanisms of innate and acquired immunity. Upon activation by
      anaphylactic, piecemeal degranulation or degranulation-independent mechanisms
      mast cells can secrete rapidly or slowly a number of soluble mediators, such as
      serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and
      growth factors. Mast cells can express cell surface co-stimulatory receptors and
      ligands, and they can express MHC class II molecules and thereby present
      antigens. These soluble factors and cell surface molecules can interact with
      other cells, such as endothelial cells, keratinocytes, sensory nerves,
      neutrophils, T cell subsets and antigen presenting cells which are essential
      effectors in the development of skin inflammation. Besides promoting
      inflammation, mast cells may attempt in some circumstances to suppress the
      inflammation and epidermal growth but the regulation between suppressive and
      proinflammatory mechanisms is unclear. Psoriasis is characterized by epidermal
      hyperplasia and chronic inflammation where tryptase- and chymase-positive MC(TC)
      mast cells are activated early in the developing lesion and later the cells
      increase in number in the upper dermis with concomitant expression of cytokines
      and TNF superfamily ligands as well as increased contacts with neuropeptide
      containing sensory nerves. Due to the intimate involvement of mast cells in
      immunity and chronic inflammation the role of mast cells in psoriasis is
      discussed in this review.

PMID- 18719934
TI  - High-resolution imaging using a novel atomic force microscope and confocal laser
      scanning microscope hybrid instrument: essential sample preparation aspects.
AB  - The recent data explosion in global gene expression profiling and proteomics has
      resulted in a need to determine the mechanistic role of biomarker signatures in
      pathogenicity. Consequently, elaborate technologies are required to assess
      increasingly smaller sub-cellular compartments and constituents. We describe the
      development, evaluation and application of an efficient sample preparation
      methodology to facilitate coupled atomic force microscopy and confocal laser
      scanning microscopy (AFM-CLSM), providing a novel means of concurrent high
      resolution structural and fluorescence imaging. Due to their fragile nature and
      nanoscale dimensions, filopodia were selected as a model to develop the procedure
      that maximised fluorescence response, while maintaining epithelial cell ultra
      structure. Fixation with ultra-pure methanol-free formaldehyde coupled to quantum
      dot nanocrystal labelling proved to be vital in achieving high quality AFM-CLSM
      images. We demonstrated for the first time that filopodia have a "quilted"
      surface structure. Additionally, high ultra-structural ridges on the apical cell
      surface resolved by AFM corresponded to punctate moesin clusters, representing
      direct visualisation of moesin linkages between transmembrane proteins and the
      cytoskeleton. The capacity of this novel multi-modal imaging technique to probe
      topography, molecular composition and biophysical properties of ultra-structural
      features therefore provides unique information that will significantly contribute
      to our understanding of cellular structure-function relationships.

PMID- 18719933
TI  - Molecular architecture of glycinergic synapses.
AB  - Synapses can be considered chemical machines, which are optimized for fast and
      repeated exocytosis of neurotransmitters from presynaptic nerve terminals and the
      reliable electrical or chemical transduction of neurotransmitter binding to the
      appropriate receptors in the postsynaptic membrane. Therefore, synapses share a
      common repertoire of proteins like, e.g., the release machinery and certain cell
      adhesion molecules. This basic repertoire must be extended in order to generate
      specificity of neurotransmission and allow plastic changes, which are considered
      the basis of developmental and/or learning processes. Here, we focus on these
      complementary molecules located in the presynaptic terminal and postsynaptic
      membrane specializations of glycinergic synapses. Moreover, as specificity of
      neurotransmission in this system is established by the specific binding of the
      neurotransmitter to its receptor, we review the molecular properties of glycine
      receptor subunits and their assembly into functional glycine receptors with
      different functional characteristics. The past years have revealed that the
      molecular machinery underlying inhibitory and especially glycinergic postsynaptic
      membrane specializations is more complex and dynamic than previously anticipated
      from morphological studies. The emerging features include structural components
      as well as signaling modules, which could confer the plasticity required for the
      proper function of distinct motor and sensory functions.

PMID- 18719935
TI  - Arseniasis prevalence and mortality in a multiethnic, endemic township in
      Guizhou, China.
AB  - OBJECTIVE: Farmers in Southwest Guizhou Autonomous Prefecture, China, represent a
      unique case of arseniasis, which is related to indoor combustion of high arsenic
      containing coal instead of to arsenic-contaminated drinking water. A significant
      difference in the prevalence of arseniasis was observed in two neighboring ethnic
      clans in one village. The question arose whether the ethnicity-dependent
      difference observed in this village was more widely spread throughout the whole
      township. An epidemiologic investigation was designed to explore arseniasis
      distribution and mortality among all four ethnic groups in a multiethnic
      township. METHODS: The cohort of arseniasis patients, diagnosed and registered in
      the overall field survey of 1991 as well as all the asymptomatic residents of the
      township, were enrolled in the present investigation. Indirect standardization
      was used for calculating the age-adjusted standardized incidence ratio (SIR) of
      arseniasis, the standardized mortality ratio (SMR) of various death causes
      (including some cancers), and their corresponding intervals of 95% confidence in
      both genders and in each local ethnic group. RESULTS: The descending rank of
      arseniasis SIRs among local ethnic groups was found as: Hui>Han>Bouyei>Hmong. The
      descending rank of SMRs of malignancies was displayed as: Han>Hui>Bouyei>Hmong in
      males and both genders together as well. Concerning deaths of non-malignant
      causes the rank was observed as: Hui>Han>Bouyei>Hmong in males. The arseniasis
      SIR for ethnic Hmong residents (both genders combined) was found to be
      significantly less profound than the overall level in the township. No death
      cases in diagnosed ethnic Hmong patients and no cases of death from malignant
      causes in asymptomatic Hmong residents were recorded. The significant increase of
      arseniasis prevalence was observed in all males, compared with the overall
      prevalence of all residents. However, a significantly lower prevalence was seen
      in all females. CONCLUSION: Significant ethnicity-dependent difference in
      arseniasis prevalence and mortality from all causes was found in a multiethnic
      rural township where farmers have been exposed to the indoor combustion of high
      arsenic coal for decades. The ethnic Hmong residents seemed to be the least
      susceptible to arseniasis among the four local ethnic groups.

PMID- 18719936
TI  - The effect of bed rest and an exercise countermeasure on leg venous function.
AB  - This study was performed to assess the effect of resistive vibration exercise
      during bed rest deconditioning on venous vascular dimension and function, as
      measured with ultrasound in the popliteal vein. Sixteen men were assigned to bed
      rest (BR-Ctrl) or bed rest with resistive vibration exercise (BR-RVE). Before and
      at 25 and 52 days of bed rest, popliteal vein diameter was measured at increasing
      cuff pressures. Venous capacitance and compliance were calculated from the
      pressure-volume curve. After 52 days of bed rest, BR-Ctrl showed no change in
      baseline popliteal vein diameter or compliance, while venous capacitance
      decreased. Resistive vibration exercise had no effect on the response in venous
      diameter, capacitance or compliance to 52 days of bed rest. The decline in venous
      capacitance due to long-term bed rest is not effectively counteracted by
      resistive vibration exercise, indicating that an alternative factor during bed
      rest deconditioning is responsible for venous changes.

PMID- 18719937
TI  - Loss of neuromuscular control related to motion in the acutely ACL-injured knee:
      an experimental study.
AB  - Ligamentomuscular and muscular stretch reflexes are known to contribute to knee
      joint stability. After anterior cruciate ligament (ACL) injury, a more intense
      and adjusted muscular response is required to maintain joint stability, but this
      neuromuscular control of the knee has not been clearly proved. The aim of the
      study is to record electromyography (EMG) signal and muscular fibre length
      variations in quadriceps and hamstrings of the knee with and without ACL, and to
      analyze and integrate the ligament strain and the muscular reaction to forced
      anterior tibial translation (ATT). In 17 knees from 12 cats, EMG electrodes and
      ultrasonomicrometry crystals were inserted into four main periarticular muscles,
      with strain gauges on periarticular ligament insertions. Their output signal was
      compared before and after ACL surgical section in series of ATT (at 90 degrees
      and 30 degrees knee flexion), and also during knee flexion and extension. Linear
      regression analysis was performed between the EMG signal and muscular fibre
      length variations, and between the EMG signal and the strain on ligament
      insertions, in the search of this reflex neuromuscular response. In the ACL
      deficient knees, the studied muscles showed a poor adjustment to motion of EMG
      firing, inversely to controls. The muscle stretch reflexes showed poorer
      correlation with post-peak EMG activity than the ligaments. ATT control depended
      mainly on hamstrings activity in control knees, whereas in unstable knees,
      quadriceps activity was associated with more tibial translation. Acute ACL
      deficient knees showed poor neuromuscular control with weak ligamentomuscular
      reflexes and no muscular stretch reflexes, suggesting the ineffectiveness of
      acute muscular reaction to provide early mechanical knee stabilization after
      injury.

PMID- 18719938
TI  - Predicting the activity phase of a follower neuron with A-current in an
      inhibitory network.
AB  - The transient potassium A-current is present in most neurons and plays an
      important role in determining the timing of action potentials. We examine the
      role of the A-current in the activity phase of a follower neuron in a rhythmic
      feed-forward inhibitory network with a reduced three-variable model and conduct
      experiments to verify the usefulness of our model. Using geometric analysis of
      dynamical systems, we explore the factors that determine the onset of activity in
      a follower neuron following release from inhibition. We first analyze the
      behavior of the follower neuron in a single cycle and find that the phase plane
      structure of the model can be used to predict the potential behaviors of the
      follower neuron following release from inhibition. We show that, depending on the
      relative scales of the inactivation time constant of the A-current and the time
      constant of the recovery variable, the follower neuron may or may not reach its
      active state following inhibition. Our simple model is used to derive a recursive
      set of equations to predict the contribution of the A-current parameters in
      determining the activity phase of a follower neuron as a function of the duration
      and frequency of the inhibitory input it receives. These equations can be used to
      demonstrate the dependence of activity phase on the period and duty cycle of the
      periodic inhibition, as seen by comparing the predictions of the model with the
      activity of the pyloric constrictor (PY) neurons in the crustacean pyloric
      network.

PMID- 18719939
TI  - Neck lesions mimicking thyroid pathology.
AB  - INTRODUCTION: Nodular lesions within the neck may origin from several structures.
      A misdiagnosed origin may expose the surgeon to inappropriate procedures. These
      lesions are paradoxically frequent in high specialised centre for endocrine
      surgery. PATIENTS AND METHODS: In the year 2006, three patients were first
      admitted to our department with a diagnosis of thyroid nodule (1) or lymphatic
      metastases of thyroid carcinoma (2). The first patient had ultrasound (US) and Tc
      99-m scan orienting for thyroid nodule. The two other patients, presented with
      lateral neck lesion in ipsilateral sincronous and previous diagnosis of papillary
      thyroid carcinoma, respectively, with US and computed tomography scan confirmed
      lesion but with a FNA cytology negative for tumoural cells. RESULTS: All three
      patients underwent surgical exploration. In the first two cases, a whitish tender
      nodule (4 and 4.5cm), cleavable from surrounding structures, was removed with
      final histology of Schwannoma and Paraganglioma, respectively. Both patients
      experienced Bernard Horner Syndrome. In the last patients, a firm grey nodule of
      5cm strictly adherent to muscular planes was removed with diagnosis of
      Castleman's Disease. CONCLUSIONS: Nodular neck lesions mimicking a thyroid
      pathology (thyroid nodules or metastatic lymph nodes) are rare but can represent
      a tough challenge for surgeons who might fall into incorrect surgical approaches,
      resulting in high morbidity. Pre-operative work-up would help the surgeon to
      obtain the correct diagnosis, thus, to follow the better surgical approach.
      Nevertheless, a careful approach would be used for that neurogenic tumour
      amenable of resection without jeopardising nervous structures.

PMID- 18719940
TI  - Transcriptomic changes in wind-exposed poplar leaves are dependent on
      developmental stage.
AB  - Responses of plant tissue to environmental challenges can vary among different
      plant parts and among plants of different ages. Investment into defense has been
      proposed to be influenced by fitness value and/or allocation of available
      resources. Here we show at first time at transcriptome level that plant defense
      is non-linear. On very young, expanding, adult and old leaves of Populus nigra
      plants exposed to air perturbation, we studied the ontogenic trajectory of gene
      expression changes to such a low-dose factor similar to wind. Although plant
      responses to mechanical sensation (wind, touch) are described and summarized as
      thigmomorphogenesis, the knowledge on the molecular background of plant responses
      to wind is largely incomplete. Our data describe which genes are activated during
      a ubiquitous and continuous environmental factor such as wind, and based on
      existing knowledge complement the picture on ongoing processes.

PMID- 18719942
TI  - Bendamustine, but not fludarabine, exhibits a low stem cell toxicity in vitro.
AB  - PURPOSE: We investigated the in vitro toxicity of bendamustine and fludarabine to
      hematopoietic progenitors and stem cells from healthy donors. METHODS: Clonogenic
      agar colony assays, non-clonogenic long-term liquid cultures (LTC) and apoptosis
      assays were used to assess the cytotoxicity of both the agents. RESULTS: Total
      colony-forming units (CFU) were more sensitive to fludarabine than to
      bendamustine in agar colony assays (IC(50) 0.7 microM/L and 8.5 microM/L,
      respectively). Using the Bliss independence model and combining the two agents
      yielded additive inhibition of progenitors. Non-clonogenic assays, including LTC
      and an apoptosis assay detecting activated caspases showed that stem cells are
      characterized by low sensitivity to bendamustine. In contrast, fludarabine
      strongly inhibited the viability and growth of stem cells in LTC. CONCLUSIONS:
      Our data show that bendamustine is characterized by lower in vitro toxicity to
      hematopoietic progenitors and stem cells than fludarabine and might thus be
      preferable in regimens prior to stem cells apheresis.

PMID- 18719941
TI  - Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus
      oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal
      cancer patients: results of the Southern Italy Cooperative Oncology study 0401.
AB  - PURPOSE: Oxaliplatin combined with either fluorouracil/leucovorin (OXAFAFU) or
      capecitabine (OXXEL) has a demonstrated activity in metastatic colorectal cancer
      patients. We aimed at comparing these two regimens in terms of response rate
      (RR), safety, progression-free survival (PFS), and quality of life (QoL) of
      patients. METHODS: A total of 322 patients with metastatic colorectal cancer were
      randomized to receive biweekly: oxaliplatin 100 mg/m(2) i.v. on day 1,
      capecitabine 1,000 mg/m(2) orally twice daily from day 1 to day 11 (OXXEL); or
      oxaliplatin 85 mg/m(2) i.v. on day 1; 6S-leucovorin 250 mg/m(2) i.v. and
      fluorouracil 850 mg/m(2) i.v. on day 2 (OXAFAFU). RESULTS: Eleven complete and 42
      partial responses were registered with OXXEL (RR = 34%); six complete and 48
      partial responses were obtained with OXAFAFU (RR = 33%) (P = 0.999). Severe
      adverse events were less frequent (32 vs. 43%) with OXXEL, which also reduced the
      occurrence of severe neutropenia (10 vs. 27%) and febrile neutropenia (6 vs.
      13%), but produced more gastric side effects (8 vs. 3%) and diarrhea (13 vs. 8%).
      QoL did not differ across the two arms. Median PFS was 6.6 months in the OXXEL,
      and 6.5 months in the OXAFAFU arm (HR = 1.12, P = 0.354). Median overall survival
      was 16.0 and 17.1 months (HR = 1.01, P = 0.883). CONCLUSIONS: OXXEL and OXAFAFU
      regimens were equally active in metastatic colorectal cancer. The choice should
      be based on patient preference and on pharmacoeconomic evaluations.

PMID- 18719943
TI  - Identification of estuarine fish Dormitator latifrons as an intermediate host and
      Eleotris picta as a paratenic host for Gnathostoma binucleatum in Sinaloa,
      Mexico.
AB  - Gnathostomosis is a typical fish-borne zoonotic parasitosis and is currently a
      serious public health issue in Mexico. Among several Gnathostoma species present
      in wild animals in Mexico, Gnathostoma binucleatum is the only proven species
      responsible for human diseases, and the advanced third stage larvae (AL3) of G.
      binucleatum have been found in over 20 species of fish in this country. In
      Sinaloa State, two fish species, Dormitator latifrons and Eleotris picta, were
      heavily contaminated with G. binucleatum AL3. When we analyzed the relationship
      between the size of the fish and the density of infection with G. binucleatum
      AL3, the distribution patterns of AL3 were markedly different between these two
      fish species. Apparent size-dependent accumulation was observed in E. picta but
      not in D. latifrons, suggesting that E. picta is a paratenic host whereas D.
      latifrons is a second intermediate host.

PMID- 18719944
TI  - Network-based model weighting to detect multiple loci influencing complex
      diseases.
AB  - For genome-wide association studies, it has been increasingly recognized that the
      popular locus-by-locus search for DNA variants associated with disease
      susceptibility may not be effective, especially when there are interactions
      between or among multiple loci, for which a multi-loci search strategy may be
      more productive. However, even if computationally feasible, a genome-wide search
      over all possible multiple loci requires exploring a huge model space and making
      costly adjustment for multiple testing, leading to reduced statistical power. On
      the other hand, there are accumulating data suggesting that protein products of
      many disease-causing genes tend to interact with each other, or cluster in the
      same biological pathway. To incorporate this prior knowledge and existing data on
      gene networks, we propose a gene network-based method to improve statistical
      power over that of the exhaustive search by giving higher weights to models
      involving genes nearby in a network. We use simulated data under realistic
      scenarios, including a large-scale human protein-protein interaction network and
      23 known ataxia-causing genes, to demonstrate potential gain by our proposed
      method when disease-genes are clustered in a network.

PMID- 18719945
TI  - Gene structure and mutant alleles of PCDH15: nonsyndromic deafness DFNB23 and
      type 1 Usher syndrome.
AB  - Mutations of PCDH15, encoding protocadherin 15, can cause either combined hearing
      and vision impairment (type 1 Usher syndrome; USH1F) or nonsyndromic deafness
      (DFNB23). Human PCDH15 is reported to be composed of 35 exons and encodes a
      variety of isoforms with 3-11 ectodomains (ECs), a transmembrane domain and a
      carboxy-terminal cytoplasmic domain (CD). Building on these observations, we
      describe an updated gene structure that has four additional exons of PCDH15 and
      isoforms that can be subdivided into four classes. Human PCDH15 encodes three
      alternative, evolutionarily conserved unique cytoplasmic domains (CD1, CD2 or
      CD3). Families ascertained on the basis of prelingual hearing loss were screened
      for linkage of this phenotype to markers for PCDH15 on chromosome 10q21.1. In
      seven of twelve families segregating USH1, we identified homozygous mutant
      alleles (one missense, one splice site, three nonsense and two deletion
      mutations) of which six are novel. One family was segregating nonsyndromic
      deafness DFNB23 due to a homozygous missense mutation. To date, in our cohort of
      557 Pakistani families, we have found 11 different PCDH15 mutations that account
      for deafness in 13 families. Molecular modeling provided mechanistic insight into
      the phenotypic variation in severity of the PCDH15 missense mutations. We did not
      find pathogenic mutations in five of the twelve USH1 families linked to markers
      for USH1F, which suggest either the presence of mutations of yet additional
      undiscovered exons of PCDH15, mutations in the introns or regulatory elements of
      PCDH15, or an additional locus for type I USH at chromosome 10q21.1.

PMID- 18719946
TI  - Leaf size and leaf display of thirty-eight tropical tree species.
AB  - Trees forage for light through optimal leaf display. Effective leaf display is
      determined by metamer traits (i.e., the internode, petiole, and corresponding
      leaf), and thus these traits strongly co-determine carbon gain and as a result
      competitive advantage in a light-limited environment. We examined 11 metamer
      traits of sun and shade trees of 38 coexisting moist forest tree species and
      determined the relative strengths of intra- and interspecific variation. Species
      specific metamer traits were related to two variables that represent important
      life history variation; the regeneration light requirements and average leaf size
      of the species. Metamer traits varied strongly across species and, in contrast to
      our expectation, showed only modest changes in response to light. Intra- and
      interspecific responses to light were only congruent for a third of the traits
      evaluated. Four traits, amongst which leaf size, specific leaf area (SLA), and
      leaf area ratio at the metamer level (LAR) showed even opposite intra- and
      interspecific responses to light. Strikingly, these are classic traits that are
      thought to be of paramount importance for plant performance but that have
      completely different consequences within and across species. Sun trees of a given
      species had small leaves to reduce the heat load, but light-demanding species had
      large leaves compared to shade-tolerants, probably to outcompete their neighbors.
      Shade trees of a given species had a high SLA and LAR to capture more light in a
      light-limited environment, whereas shade-tolerant species have well-protected
      leaves with a low SLA compared to light-demanding species, probably to deter
      herbivores and enhance leaf lifespan. There was a leaf-size-mediated trade-off
      between biomechanical and hydraulic safety, and the efficiency with which species
      can space their leaves and forage for light. Unexpectedly, metamer traits were
      more closely linked to leaf size than to regeneration light requirements,
      probably because leaf-size-related biomechanical and vascular constraints limit
      the trait combinations that are physically possible. This suggests that the leaf
      size spectrum overrules more subtle variation caused by the leaf economics
      spectrum, and that leaf size represents a more important strategy axis than
      previously thought.

PMID- 18719947
TI  - Quality of life of men treated for localized prostate cancer: outcomes at 6 and
      12 months.
AB  - GOALS OF WORK: Treatments for early-stage prostate cancer (PCa) are highly
      effective; therefore, research studies that explore quality of life (QOL) issues
      associated with different treatments are important. The purposes of this study
      were to (a) examine differences among treatment groups of men treated with either
      radiation therapies or radical prostatectomy for PCa and (b) examine quality of
      life outcomes over time. PATIENTS AND METHODS: We report outcomes 6 and 12 months
      after 159 men began treatment for PCa with either one of two types of radiation
      treatment (intensity-modulated radiation therapy plus high dose rate or intensity
      modulated radiation therapy plus seed implantation) or radical prostatectomy.
      MAIN RESULTS: Significant differences among groups are described. Significant
      predictors of QOL at 6 months included urinary, bowel, and sexual symptoms,
      anxiety, depression, problem-focused coping, and physiological self-efficacy.
      Significant predictors of QOL at 12 months were urinary and bowel symptoms,
      stress, depression, problem-focused coping, and physiological self-efficacy.
      Demographic variables, race, and living status were significant predictors of
      quality of life at 12 months. CONCLUSIONS: Physiological symptoms and
      psychological symptoms were both significant predictors of QOL. The psychological
      factors that predicted quality of life in this study have potential for
      intervention and point to the next stage of the research.

PMID- 18719948
TI  - Use of oxygen and opioids in the palliation of dyspnoea in hypoxic and non
      hypoxic palliative care patients: a prospective study.
AB  - BACKGROUND: Dyspnoea is a complex experience of the body and the mind. Whereas
      the effects of opioids on dyspnoea in advanced disease have been the focus of
      studies for management of dyspnoea in palliative medicine, the role of oxygen is
      still unclear. The effects of symptomatic oxygen and opioid treatment on
      ventilation and palliation of dyspnoea in hypoxic (H) and non-hypoxic (NH)
      palliative care patients were assessed and compared. METHODS: In a prospective,
      non-randomised study, 46 patients with mild to severe dyspnoea were included.
      Transcutaneous measurement (earlobe sensor) of carbon dioxide partial pressure
      (tcpaCO2), pulse oximetry oxygen saturation (SaO2) and pulse frequency (PF) were
      monitored with SenTec digital monitor. Compared was: baseline data of the
      continuously documented respiratory parameters for about 15 min in patients
      breathing room air at admission, 60 min during nasal O2 insufflation, and 30, 90
      and 120 min after the first opioid application and without O2 insufflation.
      RESULTS: Whereas opioid application resulted in a significant decrease in the
      intensity of dyspnoea and respiratory rate, during the nasal O2 insufflation (4
      l/min), there was no significant decrease in the intensity of dyspnoea neither in
      H (P = 0.564) nor in NH (P = 0.096) patients. There was no evidence of a
      significant correlation between the intensity of dyspnoea and oxygen saturation.
      The Spearman rank correlation in NH patients was -0.080 (P = 0.686) and in H
      patients P = 0.296 (P = 0.233). No significant differences between the groups of
      hypoxic and non-hypoxic patients with regard to tcpaCO2 increase (P = 0.075 NH; P
      = 0.346 H) or SaO2 decrease after opioid application (P = 0.077) were found.
      CONCLUSIONS: In this study, opioids worked significantly better than oxygen in
      reducing the intensity of dyspnoea even in hypoxic patients. There was no
      correlation between intensity of dyspnoea and oxygen saturation in H and NH
      patients. Oxygen should be seen as a pharmacological agent and not be given based
      on intuitive assumption of benefit.

PMID- 18719949
TI  - Response of plants to ectomycorrhizae in N-limited conditions: which factors
      determine its variation?
AB  - In the present work, the following hypotheses were tested: (1) the negative
      effects of mycorrhization over host plant productivity in N-limited conditions
      are due to N retention by the fungal partner and not due to excessive C drainage;
      (2) If mycorrhization results in decreased N uptake, the host plant decreases its
      C investment in fungal growth. The effects of mycorrhization over a wide range of
      combinations between N availability, N concentration in plant tissues, and degree
      of mycorrhizal colonization were studied in Pinus pinaster L. mycorrhizal with
      Pisolithus tinctorius. Several plant productivity parameters, the seedlings' N
      status, chl a fluorescence (JIP test), and mycorrhizal colonization were
      measured. N was always limiting. A gradient of mycorrhizal effects over the host
      plant's growth and vitality was successfully obtained. The mycorrhizal effects on
      plant growth and N uptake were very strongly and positively correlated, and no
      evidence was found of a C limitation to growth, confirming hypothesis 1.
      Indications were found that the plants continued to provide C to the fungus
      although the N supplied by it was increasingly lower, denying hypothesis 2. A new
      index, the mycorrhizal N demand-supply balance, was found to efficiently explain,
      and to have a curvilinear relation with, the variation in response to
      mycorrhization. The mycorrhizal effect on host plant growth was not related to a
      negative effect on its photosynthetic performance and, therefore, reflected
      changes in resource allocation between host plant and mycorrhizal fungus, not in
      plant vitality.

PMID- 18719950
TI  - Enzymatic activity mastered by altering metal coordination spheres.
AB  - Metalloenzymes control enzymatic activity by changing the characteristics of the
      metal centers where catalysis takes place. The conversion between inactive and
      active states can be tuned by altering the coordination number of the metal site,
      and in some cases by an associated conformational change. These processes will be
      illustrated using heme proteins (cytochrome c nitrite reductase, cytochrome c
      peroxidase and cytochrome cd1 nitrite reductase), non-heme proteins (superoxide
      reductase and [NiFe]-hydrogenase), and copper proteins (nitrite and nitrous oxide
      reductases) as examples. These examples catalyze electron transfer reactions that
      include atom transfer, abstraction and insertion.

PMID- 18719951
TI  - Determining Rieske cluster reduction potentials.
AB  - The Rieske iron-sulfur proteins have reduction potentials ranging from -150 to
      +400 mV. This enormous range of potentials was first proposed to be due to
      differing solvent exposure or even protein structure. However, the increasing
      number of available crystal structures for Rieske iron-sulfur proteins has shown
      this not to be the case. Colbert and colleagues proposed in 2000 that differences
      in the electrostatic environment, and not structural differences, of a Rieske
      proteins are responsible for the wide range of reduction potentials observed.
      Using computational simulation methods and the newly determined structure of
      Pseudomonas sp. NCIB 9816-4 naphthalene dioxygenase Rieske ferredoxin (NDO-F9816
      4), we have developed a model to predict the reduction potential of Rieske
      proteins given only their crystal structure. The reduction potential of NDO-F9816
      4, determined using a highly oriented pyrolytic graphite electrode, was -150+/-2
      mV versus the standard hydrogen electrode. The predicted reduction potentials
      correlate well with experimentally determined potentials. Given this model, the
      effect of protein mutations can be evaluated. Our results suggest that the
      reduction potential of new proteins can be estimated with good confidence from 3D
      structures of proteins. The structure of NDO-F9816-4 is the most basic Rieske
      ferredoxin structure determined to date. Thus, the contributions of additional
      structural motifs and their effects on reduction potential can be compared with
      respect to this base structure.

PMID- 18719952
TI  - The impact of cement mixing and storage errors on the risk of failure of glass
      ceramic crowns.
AB  - This study evaluated the impact of different mixing ratios and wrongly stored
      blends of dual-curing composite cements on Empress2 glass-ceramic crowns by means
      of a flexural strength test and a fracture resistance test. Thermally damaged
      blends and fresh blends were mixed using different mixing ratios of dual-curing
      Panavia F and Variolink II composite cement (2:1; 1:1; 1:1.5; 1:1.75;
      base/catalyst). Sixteen groups of rectangular beams of both cements (two blends,
      four ratios, chemical-curing, light-curing) were constructed. Their flexural
      strength was determined in a three-point bending test. Furthermore, 64 Empress2
      all-ceramic crowns were luted onto human molars, again using fresh and thermally
      damaged blends as well as different mixing ratios of the luting agents. After
      aging, fracture resistance was investigated. The flexural strength of dual-curing
      composite cements was influenced to a statistically significant extent by mixing
      ratios and storage conditions. In particular, the chemical curing mode of these
      cements was affected by the thermal damage of the blends. However, this study
      could not demonstrate a significant impact on the fracture resistance of Empress2
      glass-ceramic crowns when different mixing ratios or wrongly stored cements were
      used. Dual-curing composite luting agents seem to tolerate a wide range of mixing
      errors, but their chemical curing mode may be affected by storage errors.

PMID- 18719953
TI  - Gambling for Gatorade: risk-sensitive decision making for fluid rewards in
      humans.
AB  - Determining how both humans and animals make decisions in risky situations is a
      central problem in economics, experimental psychology, behavioral economics, and
      neurobiology. Typically, humans are risk seeking for gains and risk averse for
      losses, while animals may display a variety of preferences under risk depending
      on, amongst other factors, internal state. Such differences in behavior may
      reflect major cognitive and cultural differences or they may reflect differences
      in the way risk sensitivity is probed in humans and animals. Notably, in most
      studies humans make one or a few choices amongst hypothetical or real monetary
      options, while animals make dozens of repeated choices amongst options offering
      primary rewards like food or drink. To address this issue, we probed risk
      sensitive decision making in human participants using a paradigm modeled on
      animal studies, in which rewards were either small squirts of Gatorade or small
      amounts of real money. Possible outcomes and their probabilities were not made
      explicit in either case. We found that individual patterns of decision making
      were strikingly similar for both juice and for money, both in overall risk
      preferences and in trial-to-trial effects of reward outcome on choice. Comparison
      with decisions made by monkeys for juice in a similar task revealed highly
      similar gambling styles. These results unite known patterns of risk-sensitive
      decision making in human and nonhuman primates and suggest that factors such as
      the way a decision is framed or internal state may underlie observed variation in
      risk preferences between and within species.

PMID- 18719954
TI  - Visually guided capture of a moving stimulus by the pigeon (Columba livia).
AB  - Although the pigeon is a popular model for studying visual perception, relatively
      little is known about its perception of motion. Three experiments examined the
      pigeons' ability to capture a moving stimulus. In Experiment 1, the effect of
      manipulating stimulus speed and the length of the stimulus was examined using a
      simple rightward linear motion. This revealed a clear effect of length on capture
      and speed on errors. Errors were mostly anticipatory and there appeared to be two
      processes contributing to response locations: anticipatory peck bias and lag
      time. Using the same birds as Experiment 1, Experiment 2 assessed transfer of
      tracking and capture to novel linear motions. The birds were able to capture
      other motion directions, but they displayed a strong rightward peck bias,
      indicating that they had learned to peck to the right of the stimulus in
      Experiment 1. Experiment 3 used the same task as Experiment 2 but with naive
      birds. These birds did not show the rightward bias in pecking and instead pecked
      more evenly around the stimulus. The combined results indicate that the pigeon
      can engage in anticipatory tracking and capture of a moving stimulus, and that
      motion properties and training experience influence capture.

PMID- 18719955
TI  - Rapid detection of bla(KPC)-positive Klebsiella pneumoniae in a clinical setting.

PMID- 18719956
TI  - Prospective evaluation of pyrosequencing for the rapid detection of isoniazid and
      rifampin resistance in clinical Mycobacterium tuberculosis isolates.
AB  - A pyrosequencing-based method for the rapid detection of isoniazid (INH) and
      rifampin (RIF) resistance in Mycobacterium tuberculosis was evaluated in clinical
      practice. The method can detect the INH resistance-causing katG315 mutation, and
      all mutations in the RIF resistance-determining rpoB core region, in less than 6
      h from cultured isolates. The method was first validated with 42 isolates, and
      was subsequently prospectively evaluated with 91 isolates, including clinical
      isolates and external quality control assessment strains, over a period of 2.5
      years. The pyrosequencing results of clinical isolates were available, on
      average, 19 days earlier (median 19 days; range 3-43 days) than conventional
      susceptibility testing results. The composite data showed that the sensitivity of
      pyrosequencing for detecting resistance correctly was 66.7% for INH and 97.4% for
      RIF. The specificity of pyrosequencing was 100% for both drugs. Acceptable
      sensitivity for detecting resistance and the rapidness of pyrosequencing make it
      a valuable tool in the clinical setting.

PMID- 18719957
TI  - Probing the influence of myelin and glia on the tensile properties of the spinal
      cord.
AB  - Although glia have been historically classified as the structurally supporting
      cells of the central nervous system, their role in tissue mechanics is still
      largely unstudied. The influence of myelin and glia on the mechanical properties
      of spinal cord tissue was examined by testing embryonic day 18 chick embryo
      spinal cords in uniaxial tension following disruption of the glial matrix using
      either ethidium bromide (EB) or an antibody against galactocerebroside
      (alphaGalC) in the presence of complement. Demyelination was confirmed by myelin
      basic protein immunoreactivity and quantified using osmium tetroxide staining. A
      substantial loss of astrocytes and oligodendrocytes concurrent with demyelination
      was observed following EB injection but not alphaGalC injection. No morphological
      changes were observed following injection of saline or IgG with complement as
      controls for EB and alphaGalC. Demyelinated spinal cords demonstrated
      significantly lower stiffness and ultimate tensile stress than myelinated spinal
      cords. No significant differences were observed in the tensile response between
      the two demyelinating protocols. The results demonstrate that the glial matrix
      provides significant mechanical support to the spinal cord, and suggests that
      myelin and cellular coupling of axons via the glial matrix in large part dictates
      the tensile response of the tissue.

PMID- 18719958
TI  - A chip for catching, separating, and transporting bio-particles with
      dielectrophoresis.
AB  - This study aims at developing a 3D device for catching, separating, and
      transporting bio-particles based on dielectrophoresis (DEP). Target particles can
      be simultaneously caught and transported using the negative DEP method. In non
      uniform electric fields, the levitation height or complex permittivity of certain
      particle may be different from that of another and this property can facilitate
      separation of particles. We have designed and constructed a 3D device consisting
      of two layers of electrodes separated by a channel formed by 50 microm thick
      photoresist. The electrodes can operate effectively with 10-15 V and 5-7 MHz to
      catch all particles in the channel, and can move particles after switching the
      electric field to 5-15 V and 500-1,000 KHz. Hence, particles experienced coupling
      force of two different directional twDEP forces, and tallied with our estimation
      to move along the coupling direction.

PMID- 18719960
TI  - The 20th anniversary of the Montreal Protocol and the unexplainable 60% of ozone
      loss.

PMID- 18719959
TI  - Cobalt toxicity in anaerobic granular sludge: influence of chemical speciation.
AB  - The influence of cobalt speciation on the toxicity of cobalt to methylotrophic
      methanogenesis in anaerobic granular sludge was investigated. The cobalt
      speciation was studied with three different media that contained varying
      concentrations of complexing ligands [carbonates, phosphates and
      ethylenediaminetetraacetic acid (EDTA)]. Three fractions (nominal added,
      dissolved and free) of cobalt were determined in the liquid media and were
      correlated with data from batch toxicity experiments. The average concentration
      of cobalt that was required for 50% inhibition of methanogenic activity (IC50)
      for free Co2+ in the three sets of measurements was 13 micromol/L with a standard
      deviation of 22% and a similarity of 72% between the data obtained in the three
      different media for the range of cobalt concentrations investigated. The standard
      deviation of the IC50 for the other two fractions was much higher, i.e. 85 and
      144% for the added cobalt and dissolved cobalt, respectively, and the similarity
      was almost 0% for both fractions. Complexation (and precipitation) with EDTA,
      phosphates and carbonates was shown to decrease the toxicity of cobalt on
      methylotrophic methanogenesis. The free cobalt concentration is proposed to be
      the key parameter to correlate with cobalt toxicity. Thus, the toxicity of cobalt
      to granular sludge can be estimated based on the equilibrium-free cobalt
      concentration.

PMID- 18719961
TI  - Differences in uptake and translocation of selenate and selenite by the weeping
      willow and hybrid willow.
AB  - BACKGROUND, AIM, AND SCOPE: Due to its essentiality, deficiency, and toxicity to
      living organisms and the extensive use in industrial activities, selenium (Se)
      has become an element of global environmental and health concern. Se removal from
      contaminated sites using physical, chemical, and engineering techniques is quite
      complicated and expensive. The goal of this study was to investigate uptake and
      translocation of Se in willows and to provide quantitative information for field
      application whether Se phytoremediation is feasible and ecologically safe.
      MATERIALS AND METHODS: Intact pre-rooted plants of hybrid willows (Salix
      matsudana Koidz x alba L.) and weeping willows (Salix babylonica L.) were grown
      hydroponically and treated with selenite or selenate at 24.0 +/- 1 degrees C for
      144 h. Removal of leaves was also performed as a treatment to quantify the effect
      of transpiration on translocation and volatilization of Se. At the end of the
      study, total Se in the hydroponic solution and in different parts of plant
      tissues was analyzed quantitatively by hydride generation-atomic fluorescence
      spectrometry. The capacity of willows to assimilate both chemical forms of Se was
      also evaluated using detached leaves and roots in sealed glass vessels in vivo.
      Translocation efficiency of Se in both plants was estimated. RESULTS: Significant
      amounts of the applied selenite and selenate were eliminated from plant growth
      media by willows during the period of incubation. Both willows showed a
      significantly higher removal rate for selenate than for selenite (p < 0.05).
      Substantial differences existed in the distribution of both chemical forms of Se
      in plant materials: lower stems and roots were the major sites for accumulation
      of selenite and selenate, respectively. Translocation efficiency for selenite was
      significantly higher than that for selenate in both willow species (p < 0.01).
      Compared to the intact trees, remarkable decrease in the removal rate of both
      chemical forms of Se was found for willows without any leaves (p < 0.01).
      Volatilization of Se by plant leaves was estimated to be approximately 10% of the
      total applied selenite or selenate. Significant reduction (>20%) of selenate was
      observed in the sealed vessel with excised roots of willows, whereas trace
      amounts of selenite were eliminated from the hydroponic solution in the presence
      of roots. Detached leaves from neither of them reduced the concentration of
      selenite or selenate in the solution. DISCUSSION: Due to the significant
      difference in the removal rate and the distribution of the two chemical forms of
      Se in plant materials, the conversion of selenate to selenite in hydroponic
      solution prior to uptake and within plant tissues is unlikely. An independent
      uptake and translocation mechanisms are likely to exist for each Se chemical
      species. Uptake of selenate is mediated possibly through an active transport
      mechanism, whereas that of selenite may possibly depend on plant transpiration.
      Uptake velocities of selenite are linear (zero-order kinetics), while selenate
      removal processes obey first-order kinetics. In experiments with detached leaves
      in closed bottles, the cuticle of leaves was the major obstacle to extract both
      chemical forms of Se from the hydroponic solution. Phytovolatilization is a
      biological process playing an important role in Se removal. CONCLUSIONS: Although
      faster removal rates of selenate than selenite from plant growth media were
      observed by both willow species, selenite in plant materials was more mobile than
      selenate. Significant decrease in removal rates of both chemical forms of Se was
      detected for willows without any leaves. Significant differences in extraction,
      assimilation and transport pathways for selenite and selenate exist in willow
      trees. RECOMMENDATIONS AND PERSPECTIVES: Phytoremediation of Se is an attractive
      approach of cleaning up Se contaminated environmental sites. More detailed
      investigation on the assimilation of Se in plant roots and transport in tissues
      will provide further biochemical evidence to explain the differences in uptake
      and translocation mechanisms between selenite and selenate in willows. A relevant
      phytoremediation scheme can then be designed to clean up Se contaminated sites.
      Willows show a great potential for uptake, assimilation and translocation of both
      selenite and selenate. Phytotreatment of Se is potentially an efficient and
      practical technology for cleaning up contaminated environmental sites.

PMID- 18719963
TI  - Antifeedants and feeding stimulants in bark extracts of ten woody non-host
      species of the pine weevil, Hylobius abietis.
AB  - Bark of ten woody species, known to be rejected as a food source by the pine
      weevil, Hylobius abietis, were sequentially extracted by a Soxhlet apparatus with
      pentane followed by methanol. Species were alder (Alnus glutinosa), aspen
      (Populus tremula), beech (Fagus sylvatica), guelder rose (Viburnum opulus), holly
      (Ilex aquifolium), horse chestnut (Aesculus hippocastanum), lilac (Syringa
      vulgaris), spindle tree (Evonymus europaeus), walnut (Juglans regia), and yew
      (Taxus baccata). Bark of each species was collected in southern Scandinavia
      during the summer. Resulting extracts were tested for antifeedant activity
      against the pine weevil by a micro-feeding choice assay. At a dose corresponding
      to that in the bark, methanol extracts from Aesculus, Taxus, Ilex, and Populus
      were antifeedant active, while pentane extracts of Aesculus, Fagus, Syringa, and
      Viburnum were stimulatory. Four known antifeedants against H. abietis, the
      straight-chained carboxylic acids, hexanoic and nonanoic acid (C6 and C9),
      carvone, and carvacrol were identified by gas chromatography (GC)-mass
      spectrometry (MS) in several extracts. The major constituents were identified and
      tested for feeding deterrence. The aromatic compounds benzyl alcohol and 2
      phenylethanol are new non-host plant-derived feeding deterrents for the pine
      weevil. Additionally, two feeding stimulants, beta-sitosterol and 5
      (hydroxymethyl)-2-furaldehyde, were identified. One active methanol extract of
      Aesculus bark was sequentially fractionated by liquid chromatography, and major
      compounds were tentatively identified as branched alcohols and esters of hexanoic
      acid. Five commercially available hexanoate esters and two commercially available
      branched alcohols were identified as new active antifeedants. Both stimulatory
      and inhibiting compounds were found in the same extracts and co-eluted in the
      same or adjacent fractions. The mix of semiochemicals of opposite activity in
      each extract or fraction could explain the stimulatory-, inhibitory-, or
      sometimes neutral activity. Generally, such co-occurrence confounds the isolation
      of antifeedants.

PMID- 18719962
TI  - The realistic yield of lower leg SNAP amplitudes and SRAR in the routine
      evaluation of chronic axonal polyneuropathies.
AB  - OBJECTIVE: To assess the realistic yield of lower leg sensory nerve action
      potential amplitudes (SNAP) and the sural/radial nerve amplitude ratio (SRAR) in
      the routine evaluation of suspected distal axonal polyneuropathy. METHODS:
      Investigated were 721 people. In 393 referents without and 328 patients with
      chronic distal symmetrical polyneuropathy the SRAR, sural, superficial peroneal
      and dorsal sural SNAP were determined. RESULTS: The dorsal sural SNAP could not
      be elicited in 26 % of referents. Axonal polyneuropathy was confirmed by an
      abnormally low value of the sural or superficial peroneal SNAP or SRAR in 70 % of
      patients, and most often (68 %) by an absent sural or superficial peroneal SNAP.
      In 9 % of patients there was a normal sural but abnormal superficial peroneal
      SNAP, and 11 % had an abnormal sural but normal superficial peroneal SNAP. ROC
      curve analysis demonstrated equal accuracy of the sural and superficial peroneal
      SNAP. CONCLUSIONS: To confirm distal axonal polyneuropathy in routine clinical
      practice the sural and superficial peroneal SNAP had equal and complementary
      yield, whereas the SRAR and dorsal sural SNAP had limited additional yield.

PMID- 18719964
TI  - A prospective trial on initiation factor 4E (eIF4E) overexpression and cancer
      recurrence in node-negative breast cancer.
AB  - BACKGROUND: Eukaryotic Initiation Factor 4E (eIF4E) plays a crucial role in
      translation control. High eIF4E increase in tumor specimens independently
      predicted recurrence by multivariate analysis. This prospective trial of node
      negative only breast cancer patients was initiated to test the hypothesis that
      high eIF4E increase predicts cancer recurrence and death, independent of nodal
      status. METHODS: The trial was powered to detect a 2.4-fold increase in relative
      risk for cancer recurrence in 240 node-negative patients on the basis of high
      versus low eIF4E increase in tumor specimens (type I error = .05, statistical
      power = .08). eIF4E level was quantified by using Western blot test. Treatment
      and surveillance regimens were standardized. Primary endpoints were cancer
      recurrence and cancer-related death. RESULTS: Of the 242 patients accrued, 112
      were in the low eIF4E group (<7.5-fold), 82 were in the intermediate eIF4E group
      (7.5- to 15-fold), and 48 were in the high eIF4E group (>15-fold). Patients in
      the high eIF4E group had a statistically significant higher rate of cancer
      recurrence and cancer-related death (P = .0001 and P < or = .0001, log rank
      test). The relative risk for cancer recurrence was 2.2-fold higher in the high
      eIF4E group (P = .001, Cox model), and 3.7-fold higher for cancer-related death
      (P = .0009). CONCLUSIONS: In node-negative breast cancer, high eIF4E increase
      predicted a higher rate of cancer recurrence and death. High eIF4E patients had a
      >2-fold increase in relative risk for cancer recurrence and nearly a 4-fold
      increase in relative risk for death. This supports our hypothesis that high eIF4E
      is an independent predictor for breast cancer outcome independent of nodal
      status.

PMID- 18719965
TI  - Oncological outcome after local excision of rectal carcinomas.
AB  - BACKGROUND: Local excision (LE) of T1 rectal cancer yields low recurrence rates.
      However, more frequent recurrences with unknown states of high-risk T1/T2 tumors
      are risk factors. The purpose of this study was to evaluate if, after LE,
      immediate reoperation is required, or awaiting salvage surgery is sufficient.
      METHODS: 150 T1 and 42 T2 tumors were treated by LE. Immediate reoperation was
      attempted for unfavorable pT1 (G3-4/L1/V1/R1/Rx/R < or =1 mm) and all pT2 tumors.
      Three groups were formed. Group A included low-risk pT1 tumors after complete
      (R0) LE; unfavorable pT1 and all T2 tumors were divided in groups B (immediate
      reoperation) and C (salvage surgery). RESULTS: Groups A (n = 93) and B (n = 39)
      showed high tumor-free (TFS) and tumor-related survival (TRS) rates: group A 92%
      and 98%; group B 86% and 89%. In group C (n = 43), the TFS und TRS were
      significantly lower with 54% and 72%. Group A showed low recurrence rates and a
      wide range of International Union Against Cancer (UICC) stages. In group B,
      similarly low recurrence rates were found, but, in contrast, all recurrences were
      UICC IV. Group C had significantly higher recurrences rates and, in addition, two
      thirds of these patients showed advanced UICC stages (III-IV). CONCLUSIONS: LE of
      low-risk T1 tumors represents an adequate therapy. Immediate reoperation after LE
      of pT1 tumors with unfavorable histological finding or pT2 tumors can avoid local
      recurrences. Thereafter, high TFS rates can be expected in these patients, but
      metastases cannot be prevented and adjuvant measures are necessary. Awaiting
      recurrences as in group C leads to bad oncological outcomes with high recurrences
      and low survival rates.

PMID- 18719967
TI  - Lethal intestinal perforation after foreign body ingestion in a superobese
      patient.
AB  - Accidental ingestion of foreign bodies is common in the general population. Most
      foreign bodies pass through the entire digestive tract without incidents.
      However, in some cases, the ingested foreign body can cause complications such as
      acute abdomen due to intestinal perforation and even death. Bowel perforation may
      not be more common in the massively obese than in the normal-weight population
      but may be more problematic. We describe a super-obese female (body mass index,
      52.3 kg/m2) who underwent emergency surgery for small-bowel perforation caused by
      an ingested foreign body (fish bone); the patient died despite segmental
      intestinal resection and intensive care.

PMID- 18719968
TI  - Gastric bypass and cardiac autonomic activity: influence of gender and age.
AB  - BACKGROUND: Obesity is associated with increased sympathetic activity and higher
      mortality. Treatment of this condition is often frustrating. Roux-en-Y gastric
      bypass is the most effective technique nowadays for treatment of obesity. The aim
      of the present study is to assess the effects of this surgery on the cardiac
      autonomic activity, including the influence of gender and age, through heart rate
      variability (HRV) analysis. METHODS: The study group consisted of 71 obese
      patients undergoing gastric bypass. Time domain measures of HRV, obtained from 24
      h Holter recordings, were evaluated before and 6 months after surgery, and the
      results were compared. Percentage of interval differences of successive normal
      sinus beats greater than 50 ms (pNN50) and square root of the mean squared
      differences of successive normal sinus beat intervals (rMSSD) was used to
      estimate the short-term components of HRV, related to the parasympathetic
      activity. Standard deviation of intervals between all normal sinus beats (SDNN)
      was related to overall HRV. RESULTS: SDNN, pNN50, and rMSSD showed significant
      increase 6 months after surgery (p<0.001, p=0.001 and p=0.002, respectively). Men
      presented a greater increase of SDNN than women (p=0.006) during the follow-up.
      There was a difference in rMSSD evolution for age groups (p=0.002). Only younger
      patients presented significant increase of rMSSD. CONCLUSION: Overall HRV
      increased 6 months after surgery; this increase was more evident in men. Cardiac
      parasympathetic activity increased also, but in younger patients only.

PMID- 18719969
TI  - Glucose tolerance in the proximal versus the distal small bowel in Wistar rats.
AB  - BACKGROUND: Type 2 diabetes is an epidemic and insulin resistance is the central
      etiology of this disease. Obesity increases insulin resistance and glucose
      intolerance and also exacerbates metabolic abnormalities present in type 2
      diabetes. Bariatric surgery is the most effective treatment for severe obesity.
      Most reported series show that return to euglycemia and normal insulin levels
      occur days after gastric bypass and biliopancreatic diversion, long before major
      weight loss has taken place. The mechanisms underlying this dramatic reversal of
      type 2 diabetes following these bariatric procedures are not well understood.
      METHODS: Twelve Wistar rats were fed with a palatable hyperlipidic diet for 12
      weeks. Body weight, glucose, and intraperitoneal glucose tolerance test were
      measured regularly. On day 91, they were randomized in two groups (hindgut and
      controls) and operated. Twenty-one days later, the tests were done again and the
      hindgut group re-operated. A duodenal exclusion was done. The results of an
      intraperitoneal glucose tolerance test were compared after the procedures.
      RESULTS: Body weight increased regularly in all the rats. Some rats developed
      hyperglycemia 28 days after beginning hyperlipidic diet, but these levels
      returned to baseline on days 56 and 84. The glucose tolerance test showed an
      improvement in glycemic levels in the hindgut group 21 days after the first
      operation (151 +/- 21mg/dl). After the second operation, despite weight loss, the
      glucose tolerance test of the foregut group worsened again (267 +/- 53 mg/dl) (p
      < 0.01). CONCLUSION: Comparing the "hindgut hypothesis" and the "foregut
      hypothesis", our data show an improvement in the 30 min glucose tolerance test in
      the hindgut group.

PMID- 18719970
TI  - Fractures of the distal tibia treated with polyaxial locking plating.
AB  - We evaluated the healing rate, complications, and functional outcomes in 32 adult
      patients with very short metaphyseal fragments in fractures of the distal tibia
      treated with a polyaxial locking system. The average distance from the distal
      extent of the fracture to the tibial plafond was 11 mm. All fractures healed and
      the average time to union was 14 weeks. Six patients (19%) reported occasional
      local disturbance over the medial malleolus. There were two cases of
      postoperative superficial infections and evidence of delayed wound healing. Using
      the American Orthopaedic Foot and Ankle Society ankle score, the average
      functional score was 87.3 points (of 100 total possible points). Our results show
      the polyaxial locking plates, which offer more fixation versatility, may be a
      reasonable treatment option for distal tibia fractures with very short
      metaphyseal segments.

PMID- 18719971
TI  - Outcome of hip resurfacing arthroplasty in patients with developmental hip
      dysplasia.
AB  - Patients with osteoarthritis secondary to developmental dysplasia of the hip
      (DDH) typically are young and active, which might affect functional ratings or
      failure rates after resurfacing arthroplasty. We therefore evaluated 24 patients
      (32 hips; mean age, 44.2 years) after hip resurfacing performed for
      osteoarthritis secondary to DDH. We used the Harris hip score (HHS), the
      University of California, Los Angeles (UCLA) activity scale, and a sports and
      activity questionnaire. A radiographic analysis also was performed. We followed
      patients a minimum of 28 months (mean, 43 months; range 28-60 months). The HHS
      improved from a mean of 54.7 to 97.3 and UCLA activity levels increased from a
      mean of 5.3 to 8.6. All patients returned to sports activity at a mean of 11
      weeks after surface replacement. There were no major differences in preoperative
      and postoperative participation in the most common sports and activities. Two of
      the 32 replacements (6%) failed. We detected femoral radiolucencies in 10 of the
      remaining 30 hips. Despite satisfactory outcomes in clinical scores, return to
      sports, and hip biomechanics, the failure rate of 6% was disappointing.
      Additional followup is important to assess if failure rates increase in these
      young, active patients. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 18719972
TI  - Restoration of femoral anatomy in TKA with unisex and gender-specific components.
AB  - Recent modifications in total knee prosthesis design theoretically better
      accommodate the anatomy of the female femur and thereby have the theoretical
      potential to improve clinical results in TKA by more accurately restoring femoral
      posterior condylar offset, reducing femoral notching, reducing femoral component
      flexion, and reducing component overhang. First, we radiographically evaluated
      whether a contemporary unisex prosthesis would accommodate female anatomy equally
      as well as male anatomy. Next, we radiographically evaluated female knees in
      which a gender-specific prosthesis was used. Pre- and postoperative radiographs
      of 122 knees (42 female unisex, 41 male unisex, 39 female gender-specific) were
      reviewed. In the unisex groups, there were no differences in femoral notching or
      femoral component flexion. Posterior femoral offset increased in both groups.
      However, femoral component overhang was worse in female knees (17%) than in male
      knees (0%). In the gender-specific female group, the incidence of component
      overhang was similar to that in the unisex female group. Unisex femoral
      components of this specific design do not equally match the native anatomy male
      and female knees. In some women, a compromise was required in sizing.

PMID- 18719975
TI  - Anthropomorphic differences between the distal femora of men and women.
AB  - There is debate about whether distinct designs of femoral components for men and
      women are needed based on morphologic and size differences between genders. We
      asked whether anthropomorphic differences exist between the distal femoral
      dimensions in women and men. We measured the distal femora of 100 women and 100
      men intraoperatively after preparation for prosthetic implantation. The measured
      dimensions included the anteroposterior height from the posterior edge of the
      medial femoral condyle to the flush anterior cut, the mediolateral width at the
      transepicondylar axis, the anterior and posterior edges of the anterior chamfer,
      and the medial and lateral trochlear flanges. These measurements were compared
      between genders using independent-samples t test. The aspect ratio (a measure of
      the shape of the distal femur), the ratio between the anteroposterior and
      mediolateral dimensions, was calculated for men and women to determine whether
      there is a shape difference between genders. The mean aspect ratio was larger for
      women than for men (0.84 [range, 0.57-1.03] versus 0.81 [range, 0.066-1.34],
      respectively). The standard deviation and range of each measurement of size and
      morphology suggest variability not only between genders but also within genders.
      Whether the aspect ratios and variations will reflect clinically important
      differences in outcomes after TKA with available prostheses will require
      additional study.

PMID- 18719973
TI  - Fractures of the middle third of the tibia treated with a functional brace.
AB  - It generally is accepted that fractures of the tibia located in the proximal and
      distal thirds tend to angulate more than midshaft fractures when treated with
      intramedullary nails. We therefore compared the angular deformities and final
      shortening of 434 closed fractures located in the middle third of the tibia
      treated with a functional brace with those in fractures in the proximal and
      distal thirds treated in the same manner. Ninety-seven percent in the middle
      third healed with 8 degrees or less angulation in the mediolateral plane, which
      was a higher percentage than we had experienced in distal and proximal third
      fractures treated with this method. Nonunions occurred in four (0.9%) fractures.
      We found correlations between initial shortening, final shortening, initial
      displacement, final displacement, and time to brace with initial angulation and
      final angulation in the mediolateral and anteroposterior planes. The overall mean
      final shortening of the fractures located in the middle third was 4.3 mm. These
      experiences suggest satisfactory results can be obtained in most instances using
      a functional brace for management of closed fractures of the middle third of the
      tibia. LEVEL OF EVIDENCE: Level II, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 18719976
TI  - Does the relationship between physical activity and quality of life differ based
      on generic versus disease-targeted instruments?
AB  - BACKGROUND: There has been an increased interest in the study of physical
      activity and its relationship with quality of life (QOL) and health-related
      quality of life (HRQL) in chronic disease conditions. The investigations have
      used either generic or disease-targeted instruments for measuring QOL and HRQL,
      but have not examined differences in the associations as a function of the types
      of instruments. PURPOSE: The present study examined the associations among
      physical activity, QOL, and HRQL using generic and disease-targeted instruments
      in persons with multiple sclerosis (MS). METHODS: Participants were 292
      individuals with MS who wore an accelerometer for 7 days and then completed the
      Godin Leisure-Time Exercise Questionnaire (GLTEQ), Multiple Sclerosis Impact
      Scale-29 (MSIS-29), Leeds Multiple Sclerosis Quality of Life Scale (LMSQOL),
      Short Form-12 Health Survey (SF-12), and Satisfaction With Life Scale (SWLS).
      RESULTS: Accelerometer counts and GLTEQ scores had similarly sized correlations
      with scores from generic (SF-12) and the disease-specific (MSIS-29) measures of
      HRQL and generic (SWLS) and the disease-specific (LMSQOL) measures of QOL. Path
      analysis indicated a similar pattern of directional relationships between
      accelerometer counts and GLTEQ scores with physical and mental HRQL and, in turn,
      physical and mental HRQL with QOL using generic and disease-targeted instruments.
      CONCLUSIONS: Our results suggest that in cross-sectional analysis, physical
      activity is similarly related with QOL and HRQL using generic and disease
      targeted instruments in persons with MS.

PMID- 18719977
TI  - Prevalence of and associations with waterpipe tobacco smoking among U.S.
      university students.
AB  - BACKGROUND: Although waterpipe tobacco smoking seems to be increasing on U.S.
      university campuses, these data have come from convenience samples. PURPOSE: We
      aimed to determine the prevalence of and associations with waterpipe tobacco
      smoking among a random sample of students. METHODS: We surveyed a random sample
      of graduate and undergraduate students at a large, urban university. We used
      multivariate modeling to determine independent associations between belief
      related predictors and waterpipe tobacco smoking. RESULTS: Of the 647
      respondents, waterpipe smoking was reported in 40.5%, over the past year in
      30.6%, and over the past 30 days in 9.5%. Over half of the sample (52.1%)
      perceived that tobacco smoking from a waterpipe was less addictive than cigarette
      smoking. In fully adjusted multivariate models, 1-year waterpipe smoking was
      associated with low perceived harm (OR = 2.54, 95% CI = 1.68, 3.83), low
      perceived addictiveness (OR = 4.64, 95% CI = 3.03, 7.10), perception of high
      social acceptability (OR = 20.00, 95% CI = 6.03, 66.30), and high perception of
      popularity (OR = 4.72, 95% CI = 2.85, 7.82). CONCLUSIONS: In this sample,
      lifetime waterpipe use was as common as lifetime cigarette use. Perception of
      harm, perception of addictiveness, social acceptability, and popularity were all
      strongly related to waterpipe smoking.

PMID- 18719978
TI  - Differential regulation of human ALAS1 mRNA and protein levels by heme and cobalt
      protoporphyrin.
AB  - 5-Aminolevulinic acid synthase 1 (ALAS1) is the first and rate-controlling enzyme
      of heme biosynthesis. This study was to determine the effects of heme and
      selected nonheme metalloporphyrins on human ALAS1 gene expression in hepatocytes.
      We found that, upon heme and cobalt protoporphyrin (CoPP) treatments, ALAS1 mRNA
      levels were down-regulated significantly by ca. 50% or more. Measurement of mRNA
      in the presence of actinomycin D showed that these down-regulations were due to
      the decreases in mRNA half-lives. Furthermore, the levels of mitochondrial mature
      ALAS1 protein were down-regulated by 60-70%, but those of the cytosolic precursor
      protein were up-regulated by 2-5-fold. Measurement of protein in the presence of
      cycloheximide (CHX) suggests that elevation of the precursor form is due to the
      increase in protein half-lives. These results provide novel insights into the
      mechanisms of heme repressional effects on ALAS1 and provide a rationale for
      further investigation of CoPP as a therapeutic agent for acute porphyric
      syndromes.

PMID- 18719979
TI  - Prolonged local anesthetic action through slow release from poly (lactic acid co
      castor oil).
AB  - PURPOSE: To evaluate a new formulation of bupivacaine loaded in an injectable
      fatty acid based biodegradable polymer poly(lactic acid co castor oil) in
      prolonging motor and sensory block when injected locally. MATERIALS AND METHODS:
      The polyesters were synthesized from DL: -lactic acid and castor oil with feed
      ratio of 4:6 and 3:7 w/w. Bupivacaine was dispersed in poly(fatty ester) liquid
      and tested for drug release in vitro. The polymer p(DLLA:CO) 3:7 loaded with 10%
      bupivacaine was injected through a 22G needle close to the sciatic nerve of ICR
      mice and the duration of sensory and motor nerve blockade was measured. RESULTS:
      The DL: -lactic acid co castor oil p(DLLA:CO) 3:7 released 65% of the
      incorporated bupivacaine during 1 week in vitro. Single injection of 10%
      bupivacaine loaded into this polymer caused motor block that lasted 24 h and
      sensory block that lasted 48 h. CONCLUSION: Previously we developed a ricinoleic
      acid based polymer with incorporated bupivacaine which prolonged anesthesia to 30
      h. The new polymer poly(lactic acid co castor oil) 3:7 provides slow release of
      effective doses of the incorporated local anesthetic agent and prolongs
      anesthesia to 48 h.

PMID- 18719980
TI  - Effect of the intravenous lipid emulsions on the availability of calcium when
      using organic phosphate in TPN admixtures.
AB  - PURPOSE: The addition of high amounts of calcium remains a pharmaceutical concern
      due to its precipitation with phosphate in total parenteral nutrient (TPN)
      admixtures, compromising also the stability of the lipid emulsion. MATERIALS AND
      METHODS: Calcium-phosphate solubility was compared when using binary PN solutions
      versus all-in-one TPN (admixtures with lipid emulsions) in three formulas using
      organic calcium gluconate and glucose-1-phosphate. RESULTS: It was found that
      variation of Ca-P solubility exists between formulation with or without lipid
      emulsions. Concentrations of Ca decreased after filtrations of all admixtures
      (from 5% to 30%) and it was more significant in binary solutions. Precipitation
      has been observed by microscopy at high concentrations of both organic Ca-P after
      critical conditions of storage (24 h at 37 degrees C plus one day at ambient
      temperature) for admixtures containing 1% amino acids and 8% glucose with or
      without lipids compared to admixtures containing 2% or 3.5% amino acids and 14%
      glucose. CONCLUSIONS: These data demonstrated that availability of Ca using
      organic glucose-1-phosphate increased when lipids were present in TPN admixtures,
      without alteration of the lipid emulsion. Thus, high amounts of Ca (up to 30
      mmol/l) and phosphates (up to 40 mmol/l) might be provided safely in parenteral
      nutrition admixtures.

PMID- 18719982
TI  - Living with long QT syndrome: a qualitative study of coping with increased risk
      of sudden cardiac death.
AB  - Long QT syndrome (LQTS) is a congenital disorder associated with increased risk
      of sudden cardiac death; LQTS patients and their families are offered diagnostic
      or predictive genetic testing. The purpose of this qualitative study was to
      investigate the psychosocial aspects of living with LQTS, to identify LQTS
      patients' daily life challenges and coping strategies, and to describe their
      experiences with healthcare services. In-depth interviews were conducted with
      seven individuals who had been tested for long QT genetic mutation. Four of these
      participants had an implantable cardiac defibrillator (ICD). The participants
      reported that early and gradually acquired knowledge of the syndrome was an
      advantage. They also reported experiencing worries and limitations in daily life,
      but their main concern was for their children or grandchildren. Healthcare
      providers' minimal knowledge of LQTS resulted in uncertainty, misinformation, and
      even wrong advice regarding treatment. The results suggest that regional centers,
      with the appropriate expertise, should investigate and counsel LQTS patients and
      their families.

PMID- 18719981
TI  - A review of assessment tools of illness representations: are these adapted for a
      work disability prevention context?
AB  - INTRODUCTION: Musculoskeletal disorders are among the main causes of short- and
      long-term disability. AIM: Identify the methods for assessing multidimensional
      components of illness representations. METHODS: An electronic literature search
      (French, English) from 1980 to the present was conducted in medical, paramedical
      and social science databases using predetermined key words. After screening
      titles and abstracts based on a specific set of criteria, sixty-four articles
      were reviewed. RESULTS: Qualitative approaches for assessing illness
      representation were found mainly in the fields of anthropology and sociology and
      were based on the explanatory models of illness. The interviews reviewed were:
      the Short Explanatory Model Interview, the Explanatory Model of Illness Catalogue
      and the McGill Illness Narrative Interview. Quantitative approaches were found in
      the health psychology field and used the following self-administered
      questionnaires: the Survey of Pain Attitudes, the Pain Beliefs and Perceptions
      Inventory, the Pain Beliefs Questionnaire, the Fear-Avoidance Beliefs
      Questionnaire, the Implicit Model of Illness Questionnaire, the Illness
      Perception Questionnaire, including its derivatives, and the Illness Cognition
      Questionnaire. CONCLUSION: This review shows the actual use and existence of
      multiple interviews and questionnaires in assessing multidimensional illness
      representations. All have been used and/or tested in a medical context but none
      have been tested in a work disability context. Further research will be needed to
      determine their suitability for use in a work disability context.

PMID- 18719983
TI  - Eyewitness memory of a supermarket robbery: a case study of accuracy and
      confidence after 3 months.
AB  - In this case study, 14 witnesses of an armed robbery were interviewed after 3
      months. Security camera recordings were used to assess memory accuracy. Of all
      information that could be remembered about 84% was correct. Although accurately
      recalled information had a higher confidence level on average than inaccurately
      recalled information, the mean accuracy-confidence correlation was rather modest
      (0.38). These findings indicate that confidence is not a reliable predictor of
      accuracy. A higher level of self-reported, post-event thinking about the incident
      was associated with higher confidence levels, while a higher level of self
      reported emotional impact was associated with greater accuracy. A potential
      source of (mis)information, a reconstruction of the robbery broadcasted on TV,
      did not alter the original memories of the witnesses.

PMID- 18719984
TI  - The impact of pregnancy on physical activity level.
AB  - OBJECTIVE: The purpose of this study was to compare women's levels of physical
      activity during early pregnancy and during the year before pregnancy, and to
      identify characteristics associated with discontinuing sports and exercise among
      women previously active during the year before pregnancy. METHODS: Data collected
      from 1,737 women enrolled in a prospective cohort study and who had no
      contraindications for exercise were included in this analysis. Measures of
      physical activity (including household and care-giving activities, active living
      and sports and exercise activities) during early pregnancy were compared to the
      year before pregnancy. Log binomial regression was used to identify factors
      associated with discontinuing sports and exercise during pregnancy. RESULTS:
      There was a statistically significant decrease in all summary measures of
      physical activity during early pregnancy. The largest decreases were observed in
      sports and exercise activity. Among women active before pregnancy, age <35 years,
      multiparity, less than university education, pre-pregnancy body mass index (BMI)
      > or = 30 kg/m(2) and lower levels of pre-pregnancy exercise were associated with
      discontinuing sports and exercise activities during pregnancy. CONCLUSION: Most
      women reduced their physical activity level during the first 20 weeks of
      pregnancy compared with their level of activity during the year prior to
      pregnancy, particularly for sports and exercise, although a small proportion of
      women in this study actually increased their activity in this area during early
      pregnancy. Participation in sports and exercise activity during pregnancy is
      potentially modifiable and could favorably impact perinatal health and maternal
      post-partum weight. The results of this study suggests that pregnancy is an event
      that leads to a decrease in physical activity.

PMID- 18719985
TI  - Progress towards narrowing health disparities: first steps in sorting out infant
      mortality trend improvements among American Indians and Alaska Natives (AI/ANs)
      in the Pacific Northwest, 1984-1997.
AB  - BACKGROUND: Most AI/AN infant mortality rates (IMRs) remain higher than white
      rates. The Northwest Portland Area Indian Health Board (NPAIHB), serving 43
      tribes, CDC and the Washington, Oregon, and Idaho health departments investigated
      AI/AN infant survival. METHODS: NPAIHB completed linking computerized birth
      certificate and birth-death files. We used death and birth cohorts, StatXact and
      SAS to compare 3-state resident, single and multi-year IMRs, basing infant race
      on mother's race, regardless of Hispanic origin. We used CDC's National Infant
      Mortality Surveillance ICD-9 categories for cause-specific rates. RESULTS: From
      1984 to 1997, about 2100-2800 AI/AN births occurred annually. From 1984 to 1990,
      AI/AN IMRs were 1.8-2.4 fold higher than white rates. Then aggregate-year IMRs
      significantly declined from 16.3 in 1984-1987 to 6.7 in 1994-1997 (P < 0.0001),
      approaching the 5.6 1994-1997 white rate. In 1998 the AI/AN IMR rate increased to
      10.3. AI/AN SIDS and respiratory distress syndrome rates decreased significantly,
      respectively, from 8.1 in between 1984-1987 to 2.3 in 1994-1996 and from 1.8 in
      1984-1987 to 0.3 in 1991-1993, then leveled off. Significant rate declines
      occurred among most demographic, risk behavior, birthweight, gestational-age,
      reproductive risk, birth spacing, and labor/delivery sub-groups. Among others,
      AI/AN residents in Idaho as well as those who received no prenatal care and who
      had 0-5 month birth spacing experienced no improvements. CONCLUSIONS: These
      uncommon rate declines imply multi-factorial improvements among Northwest AI/ANs.
      Community-level surveillance and interventions before conception through post
      partum may further improve health. Collaborative efforts need to be maintained to
      continue to monitor changes in AI/AN infant health and maternal characteristics.

PMID- 18719986
TI  - The child play behavior and activity questionnaire: a parent-report measure of
      childhood gender-related behavior in China.
AB  - Boys and girls establish relatively stable gender stereotyped behavior patterns
      by middle childhood. Parent-report questionnaires measuring children's gender
      related behavior enable researchers to conduct large-scale screenings of
      community samples of children. For school-aged children, two parent-report
      instruments, the Child Game Participation Questionnaire (CGPQ) and the Child
      Behavior and Attitude Questionnaire (CBAQ), have long been used for measuring
      children's sex-dimorphic behaviors in Western societies, but few studies have
      been conducted using these measures for Chinese populations. The current study
      aimed to empirically examine and modify the two instruments for their
      applications to Chinese society. Parents of 486 Chinese boys and 417 Chinese
      girls (6-12 years old) completed a questionnaire comprising items from the CGPQ
      and CBAQ, and an additional 14 items specifically related to Chinese gender
      specific games. Items revealing gender differences in a Chinese sample were
      identified and used to construct a Child Play Behavior and Activity Questionnaire
      (CPBAQ). Four new scales were generated through factor analysis: a Gender Scale,
      a Girl Typicality Scale, a Boy Typicality Scale, and a Cross-Gender Scale (CGS).
      These scales had satisfactory internal reliabilities and large effect sizes for
      gender. The CPBAQ is believed to be a promising instrument for measuring
      children's gender-related behavior in China.

PMID- 18719987
TI  - Sex-specific content preferences for visual sexual stimuli.
AB  - Although experimental studies support that men generally respond more to visual
      sexual stimuli than do women, there is substantial variability in this effect.
      One potential source of variability is the type of stimuli used that may not be
      of equal interest to both men and women whose preferences may be dependent upon
      the activities and situations depicted. The current study investigated whether
      men and women had preferences for certain types of stimuli. We measured the
      subjective evaluations and viewing times of 15 men and 30 women (15 using
      hormonal contraception) to sexually explicit photos. Heterosexual participants
      viewed 216 pictures that were controlled for the sexual activity depicted, gaze
      of the female actor, and the proportion of the image that the genital region
      occupied. Men and women did not differ in their overall interest in the stimuli,
      indicated by equal subjective ratings and viewing times, although there were
      preferences for specific types of pictures. Pictures of the opposite sex
      receiving oral sex were rated as least sexually attractive by all participants
      and they looked longer at pictures showing the female actor's body. Women rated
      pictures in which the female actor was looking indirectly at the camera as more
      attractive, while men did not discriminate by female gaze. Participants did not
      look as long at close-ups of genitals, and men and women on oral contraceptives
      rated genital images as less sexually attractive. Together, these data
      demonstrate sex-specific preferences for specific types of stimuli even when,
      across stimuli, overall interest was comparable.

PMID- 18719989
TI  - Physical development and sexual orientation in men and women: an analysis of
      NATSAL-2000.
AB  - In the present study, three physical development characteristics-weight, height,
      and age of menarche-were examined for their relation to sexual orientation.
      Participants were men and women comprising the National Survey of Sexual
      Attitudes and Lifestyles-2000 (N > 11,000). Participants completed self-report
      measures of sexual orientation, height, weight, and, for women, age of menarche.
      Results indicated that gay/bisexual men were significantly shorter and lighter
      than heterosexual men. There were no significant differences between lesbians and
      heterosexual women in height, weight, and age of puberty. The results add to
      literature suggesting that, relative to heterosexual men, gay/bisexual men may
      have different patterns of growth and development because of early biological
      influences (e.g., exposure to atypical levels of androgens prenatally). However,
      the present results do not support a number of studies suggesting that
      lesbian/bisexual women are taller and heavier than heterosexual women.

PMID- 18719988
TI  - Moderators of sexual behavior in gay men.
AB  - We investigated factors that might moderate the association between sexual
      behavior desires and sexual behavior enactments in gay men. Condom eschewal,
      number of STIs, HIV serostatus, age, and relationship status were each
      hypothesized to moderate this association. An Internet survey collected data from
      219 self-identifying gay men. Results indicated that sexual behavior desires and
      enactments were highly correlated, and of the five moderators tested, four varied
      this association. Condom eschewers had a stronger association between desires and
      enactments than condom users. Gay men with fewer STIs/STDs (excluding HIV) also
      had a stronger association between the two variables. HIV serostatus did not
      exclusively moderate the association. Rather, a three-way interaction was
      produced such that HIV-positive men with STIs had a stronger association between
      sexual behavior desires and enactments than HIV-negative men with STIs. Finally,
      gay men in monogamous relationships were least likely to have their desires
      associated with enactments. Age was not found to be a significant moderator.
      Overall, we concluded the moderators representing sexual health and sexual health
      behaviors were most influential over the enactment of sexual behavior desires.

PMID- 18719990
TI  - Depression predicts failure to complete phase-II cardiac rehabilitation.
AB  - Reduced adherence to medical treatment regimens may help to explain the higher
      risk of mortality among depressed cardiac patients. Participation in cardiac
      rehabilitation is a highly recommended part of the medical treatment regimen for
      cardiac patients. This study examined if elevated depressive symptomology, as
      measured by the Beck Depression Inventory (BDI), predicted failure to complete a
      12-week phase II cardiac rehabilitation program for 600 patients. Logistic
      regression analysis showed that patients with elevated levels of depressive
      symptomology (BDI scores > or = 10) were 2.2 times less likely to complete
      cardiac rehabilitation compared to patients without depression (BDI < 10), after
      controlling for age, gender, body mass index, and employment. Somatic symptoms
      predicted non-completion due to medical reasons, whereas younger age predicted
      failure to complete cardiac rehabilitation due to non-medical reasons. Given the
      difficulty of reducing mortality by treating depression directly, interventions
      targeting behavior change to improve medical treatment adherence might be an
      effective complementary strategy.

PMID- 18719991
TI  - Maternal and genetic effects on the acoustic startle reflex and its sensitization
      in C3H/HeN, DBA/2JHd and NMRI mice following blastocyst transfer.
AB  - In the present study, reciprocal embryo transfers were conducted to examine
      genetic and maternal effects on the baseline and fear-sensitized acoustic startle
      response (ASR) in the two inbred strains C3H/HeN and DBA/2JHd and the outbred
      strain NMRI. The largest differences in the ASR were found in untreated strains
      (effect size 0.6). The transfer procedure per se had a significant effect on the
      behavior of NMRI mice resulting in a reduction in the baseline, and an increase
      in the fear-sensitized ASR. In contrast, there were no significant effects of the
      transfer procedure in the two inbred strains. Autosomal genetic effects had a
      stronger impact on the amplitude of the ASR (effect sizes 0.5) than sex (effect
      sizes 0.06) as revealed by reciprocal embryo transfer. Nevertheless, the genetic
      effects on the fear-sensitized ASR were somewhat more variable and strain
      dependent (effect sizes 0.1-0.2). Global maternal effects were detected after
      embryo transfer into NMRI mothers resulting in a larger reduction of the ASR in
      the offspring of DBA and NMRI donors than C3H donors (effect sizes 0.1-0.2). An
      additional fostering procedure was introduced to dissect uterine and postnatal
      maternal effects in NMRI offspring. Uterine factors changed the baseline ASR of
      the offspring in direction of the recipient mother strain. Surprisingly,
      postnatal maternal effects on the ASR were contrary to the behavior of the
      rearing mother. In conclusion, both genetic and prenatal/postnatal maternal
      factors persistently influenced the ASR of the offspring, whereas the fear
      sensitized ASR was mainly influenced by genetic factors. Our study shows that
      uterine and postnatal maternal influences deserve more attention when determining
      the phenotype of genetically engineered mice at least in the first generation
      following embryo transfer.

PMID- 18719992
TI  - Oligometastatic breast cancer treated with curative-intent stereotactic body
      radiation therapy.
AB  - PURPOSE: Prospective pilot study to assess patient outcome after stereotactic
      body radiation therapy (SBRT) for limited metastases from breast cancer. METHODS:
      Forty patients with < or =5 metastatic lesions received curative-intent SBRT,
      while 11 patients with >5 lesions, undergoing SBRT to < or =5 metastatic lesions,
      were treated with palliative-intent. RESULTS: Among those treated with curative
      intent, 4-year actuarial outcomes were: overall survival of 59%, progression-free
      survival of 38% and lesion local control of 89%. On univariate analyses, 1
      metastatic lesion (versus 2-5), smaller tumor volume, bone-only disease, and
      stable or regressing lesions prior to SBRT were associated with more favorable
      outcome. Patients treated with palliative-intent SBRT were spared morbidity and
      mortality from progression of treated lesions, though all developed further
      metastatic progression shortly (median 4 months) after enrollment. CONCLUSIONS:
      SBRT may yield prolonged survival and perhaps cure in select patients with
      limited metastases. Palliative-intent SBRT may be warranted for symptomatic or
      potentially symptomatic metastases.

PMID- 18719993
TI  - Acute and chronic cadmium toxicity to a saltwater cladoceran Moina monogolica
      Daday and its relative importance.
AB  - Acute and chronic toxicity tests of a saltwater cladoceran Moina monogolica Daday
      exposed to cadmium were conducted according to the American Society for Testing
      and Materials (ASTM) guidelines. The 24- and 48-h LC50s and their 95% confidence
      intervals (CIs) were calculated as 9.59 (8.91-10.26) and 1.87 (1.46-2.32) mg
      Cd/l, respectively, based on measured cadmium concentrations. When compared with
      different phyla or classes of saltwater animals, M. monogolica had moderate
      sensitivity and was suitable to be used as an indicator organism. Eight end
      points used to evaluate chronic effects were affected at chronic cadmium
      concentrations. Test organisms ceased to reproduce when exposed to equal to or
      greater than 308.10 microg Cd/l. Comparisons of chronic effects showed that
      mechanisms of metal accumulation patterns M. monogolica exposed to cadmium are
      different from those of dissolved copper exposure. The point estimates using
      linear regression equations of net reproductive rate generated the maximum
      acceptable-toxicant concentration of 1.78 microg Cd/l, the lowest-observed-effect
      concentration of 3.01 microg Cd/l and the no-observed-effect concentration of
      1.11 microg Cd/l. Comparisons among thresholds, cadmium concentrations in natural
      aquatic systems and water quality criteria showed that aquatic organisms were
      possibly negatively affected at some sites of higher cadmium concentrations.
      Further research is needed to focus on risk assessment of cadmium on saltwater
      aquatic organisms and water quality criteria development of China.

PMID- 18719994
TI  - Nestin in the temporal neocortex of the intractable epilepsy patients.
AB  - Nestin is one kind of intermediate filament protein, which is considered as a
      typical marker of neural precursor cells. Considerable evidence supports nestin
      may have actively functions in neurogenesis and gliosis. Our aim was to
      investigate nestin expression in the temporal neocortex of patients with
      intractable epilepsy (IE), and then to discuss the possible role of nestin in IE.
      Tissue samples from the temporal neocortex of 32 patients who had surgery for IE
      were used to detect nestin expression by immunohistochemistry,
      immunofluorescence. We compared these tissues with 12 histologically normal
      temporal neocortex from intracranial hypertension patients who had decompression
      procedures. In this study, we found some nestin positive cells in the normal
      temporal neocortex, but in the intractable epilepsy, they were upregulated,
      increasing with length of course and seizure frequency. Optical density (OD)
      value in epileptic tissue was determined 0.246 +/- 0.030, and 0.134 +/- 0.040 in
      the control (P < 0.05). Double lables of immunofluorescence showed some nestin
      positive cells coexpression with glial fibrillary acidic protein (GFAP), while
      some coexpression with microtubule-associated protein-2 (MAP(2)). These findings
      provided some evidence for increased neurogenesis and gliosis in epilepsy, which
      could be associated with intractable epilepsy.

PMID- 18719995
TI  - Electroacupuncture in the treatment of obesity.
AB  - Obesity is becoming one of the most common health problems in the world. Many
      other disorders, such as hypertension and diabetes are considered as the
      consequences of obesity. Since effective remedies are rare (only two drugs,
      Orlistat and Sibutramine, were officially approved by the US Food and Drug
      Administration for long-term obesity treatment so far), researchers are trying to
      discover new therapies for obesity, and acupuncture is among the most popular
      alternative approaches. To facilitate weight reduction, one can use manual
      acupuncture, electroacupuncture (EA) or transcutaneous electrical acupoint
      stimulation (TEAS). As the parameters of the EA or TEAS can be precisely
      characterized and the results are more or less reproducible, this review will
      focus on EA as a treatment modality for obesity. Results obtained in this
      laboratory in recent five years will be summarized in some detail.

PMID- 18719996
TI  - Chronic administration of mood stabilizers upregulates BDNF and bcl-2 expression
      levels in rat frontal cortex.
AB  - Brain-derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2) proteins
      are neuroprotective factors involved in neuronal signaling, survival and
      plasticity. Both can be regulated by cyclic AMP response element binding (CREB)
      protein. Decreased levels of BDNF and Bcl-2 are implicated in the pathogenesis of
      bipolar disorder. The present study investigated whether chronically administered
      mood stabilizers would increase BDNF and/or Bcl-2 levels in rat brain. Real time
      RT-PCR, sandwich ELISA and Western blotting were used to measure BDNF and Bcl-2
      mRNA and protein levels in the frontal cortex of rats chronically administered
      carbamazepine (CBZ) or lamotrigine (LTG) to produce plasma concentrations
      therapeutically relevant to bipolar disorder. Chronic CBZ and LTG significantly
      increased BDNF and Bcl-2 mRNA and protein levels in the frontal cortex. A common
      mechanism of action of mood stabilizers in the treatment of bipolar disorder may
      involve neuroprotection mediated by upregulation of brain BDNF and Bcl-2
      expression.

PMID- 18719997
TI  - Lysosulfatide regulates the motility of a neural precursor cell line via calcium
      mediated process collapse.
AB  - Lysosulfatide is a derivative of the glycosphingolipid sulfatide. It is a major
      component of high density lipoproteins and was detected in the human brain. Here,
      we show that lysosulfatide acts as an extracellular signal regulating the
      migration of a neural precursor cell line (B35 neuroblastoma cells) by rapidly
      promoting process retraction and cell rounding. These cells express the
      lysosulfatide receptor S1P3 according to RT-PCR, western blotting and
      immunocytochemistry, but S1P3 does not mediate the effect since preincubation
      with three different compounds known to inhibit S1P3 did not block lysosulfatide
      induced cell rounding. The signal transduction after stimulation with 3 microM
      lysosulfatide involves a rapid increase of [Ca2+]i which causes process
      retraction. This mechanism may be relevant under conditions where neural cells
      encounter elevated lysosulfatide levels as for example under pathological
      conditions after breakdown of the blood brain barrier or possibly in the
      lysosomal sulfatide storage disorder metachromatic leukodystrophy.

PMID- 18719998
TI  - Relation of matrix metalloproteinase-9 to different stages of tumors in the serum
      of gastric cancer.
AB  - The sera of 40 patients with gastric cancer and 11 patients as the control group
      were studied for the detection of matrix metalloproteinases. The malignant
      behavior of tumor cells mainly depends on the capability of invasion and the
      metastasis of cancer cells. After the components of the extracellular matrix
      (ECM) are degraded, tumor cells invade the surrounding tissue and the vascular or
      lymphatic vessels to form metastasis colonies at distant sites. Extracellular
      proteolytic enzymes implicate the invasion and metastasis of cancer. Proteolytic
      enzymes from tumors lead to the breakdown of basement membranes and the ECM,
      thereby, facilitating cancer cell invasion into the surrounding normal tissue.
      Proteinase activity is overexpressed in the serum of stage 3 and 4 tumors
      compared to stage 1 and 2 tumors. ProMMP-9 was detected in the serum of patients
      of gastric cancer by SDS polyacrylamide gel electrophoresis (SDS-PAGE) and SDS
      PAGE zymography, with its molecular mass of 92 kDa. MMP-9 in serum plays an
      important role in the progression of gastric cancer.

PMID- 18719999
TI  - Abdominal surgery affects small bowel transit time and completeness of capsule
      endoscopy.
AB  - The aim of the study was to evaluate bowel dysmotility in patients with a history
      of abdominal surgery by measuring both gastric transit time and small bowel
      transit time during capsule endoscopy and assessing the completeness of the
      examination. The study included 26 patients who had undergone abdominal surgery
      (postoperative group) and 52 patients who had not (control group). The capsule
      reached the cecum in 50.0% of the postoperative group and 80.8% of the control
      group (P=0.005). While there was no significant difference in gastric transit
      time between the two groups (P=0.882), small bowel transit time was significantly
      longer in the postoperative group (338.3+/-119.2 min) than in the control group
      (266.4+/-110.8 min, P=0.010). This is the first study to report that the small
      bowel transit time during capsule endoscopy is prolonged in patients who had a
      history of abdominal surgery, resulting in a lower frequency of complete
      examination.

PMID- 18720000
TI  - The simultaneous expression of peroxisome proliferator-activated receptor delta
      and cyclooxygenase-2 may enhance angiogenesis and tumor venous invasion in
      tissues of colorectal cancers.
AB  - We conducted this study to evaluate the impact of the expression of peroxisome
      proliferator-activated receptor delta on angiogenesis in tissue samples of
      colorectal cancer. We examined 52 samples of primary human colorectal carcinomas
      and matched normal adjacent tissues to evaluate the expression of peroxisome
      proliferator-activated receptor delta, cyclooxygenase-2, vascular endothelial
      growth factor-A, and CD34 through immunohistochemical analysis. Peroxisome
      proliferator-activated receptor delta was expressed in 25 (48.1%), and
      cyclooxygenase-2 was expressed in 26 (50.0%) of total colorectal cancer tissues.
      Tissue samples were divided into four groups, according to the expression of
      peroxisome proliferator-activated receptor delta and cyclooxygenase-2. The
      positive rate of vascular endothelial growth factor-A, the levels of
      microvascular density, and the incidence of venous vessel invasion in peroxisome
      proliferator-activated receptor delta (+)/cyclooxygenase-2 (+) samples exceeded
      significantly those in the other three groups of tissue samples (P<0.05). The
      results suggest that the axis of the cyclooxygenase-2/peroxisome proliferator
      activated receptor delta signal pathway might play a crucial role in the
      development of colorectal cancers by enhancing angiogenesis.

PMID- 18720001
TI  - The effects of melatonin on colonic transit time in normal controls and IBS
      patients.
AB  - OBJECTIVES: The role of melatonin in regulating gut motility in human subjects is
      not clear. The aim of this study was to investigate the effects of exogenous
      melatonin on colonic transit time (CTT) in healthy subjects and in patients with
      irritable bowel syndrome (IBS). METHODS: Colonic transit time was measured in 17
      healthy controls using the radio-opaque, blue dye, and Bristol stool form score
      method before and after 30 days of melatonin treatment 3 mg daily. A double blind
      cross-over study aimed at measuring CTT was also performed in 17 matched IBS
      patients using the blue dye and Bristol stool form score methods. The patients
      were randomized and received either melatonin 3 mg or placebo daily for 8 weeks,
      followed by a 4-week washout, and then placebo or melatonin in the reverse order
      for a second 8-week period. RESULTS: The melatonin treatment of the control
      subjects caused an increase in CTT (mean+/-SD) from 27.4+/-10.5 to 37.4+/-23.8 h
      (P=0.04). Compared with the CTT of the controls (25.2+/-7.7), that of the
      constipation-predominant IBS patients appeared prolonged-65.2+/-33.3 h (P<0.01).
      The CTT did not change significantly in IBS patients after melatonin treatment.
      CONCLUSION: Melatonin may be a promising candidate for the future research of
      agents that can modulate bowel motility.

PMID- 18720002
TI  - Irritable bowel syndrome and gastroesophageal reflux disease in primary care: is
      there a link?
AB  - Population-based studies have shown that gastroesophageal reflux disease (GERD)
      and irritable bowel syndrome (IBS) coexist more commonly than expected by chance.
      We aimed to investigate the relationship between GERD and IBS in primary care.
      The General Practice Research Database was used to identify patients with a first
      diagnosis of GERD (n=6,421) or IBS (n=2,932). Patients were followed up for 12
      months after diagnosis to investigate the incidence of IBS among GERD patients
      and GERD among IBS patients. The relative risk (RR) of developing IBS was 3.5
      (95% CI: 2.3-5.4) in the GERD cohort compared with the comparison cohort. The RR
      of developing GERD was 2.8 (95% CI: 1.7-4.9) in the IBS cohort compared with the
      comparison cohort. A first diagnosis of either IBS or GERD significantly
      increases the risk of a subsequent diagnosis of the other condition.

PMID- 18720003
TI  - Conjugated linoleic acid-induced toxic hepatitis: first case report.
AB  - A 46-year-old female patient was referred to our department with presenting
      symptoms of asthenia, jaundice, and pruritus. There was no medical history or
      clinical evidence of viral hepatitis, autoimmune hepatitis, hemochromatosis, or
      Wilson's disease. The patient revealed that 14 days prior to admission she had
      begun self-medicating with conjugated linoleic acid (CLA) to reduce body fat,
      leading to the suspicion of CLA hepatotoxicity, which was subsequently confirmed
      by a liver biopsy. After the patient ceased to ingest CLA, liver enzymes levels
      normalized. To the best of our knowledge, this is the first report of
      hepatotoxicity due to CLA ingestion.

PMID- 18720004
TI  - Mutational analysis of WTX gene in Wnt/ beta-catenin pathway in gastric,
      colorectal, and hepatocellular carcinomas.
AB  - A recent study of Wilms' tumors discovered a new X chromosome gene, Wilms' tumor
      gene on the X chromosome (WTX), which was found to harbor small deletions and
      point mutations. WTX protein negatively regulates Wnt/ beta-catenin signaling,
      and is considered a tumor-suppressor gene. One of the questions about the WTX
      gene is whether the genetic alterations of the WTX gene are specific to only
      Wilms' tumors. To see whether somatic point mutations of WTX occur in other
      malignancies, we analyzed the WTX gene for the detection of mutations in 141
      cancer tissues by a single-strand conformation polymorphism assay. The cancer
      tissues consisted of 47 gastric adenocarcinomas, 47 colorectal adenocarcinomas,
      and 47 hepatocellular carcinomas. Overall, we detected one WTX mutation in the
      colorectal carcinomas (1/47; 2.1%), but there was no WTX mutation in other
      cancers analyzed. The detected mutation was a missense mutation (c. 1117G > A
      (p.Ala373Thr)). Although the WTX mutation is common in Wilms' tumors, our data
      indicate that it is rare in colorectal, gastric, and hepatocellular carcinomas.
      The data also suggest that deregulation of Wnt/ beta-catenin signaling by WTX
      gene mutation may be a rare event in the pathogenesis of colorectal, gastric, and
      hepatocellular carcinomas.

PMID- 18720005
TI  - Severe cholestasis and renal failure associated with the use of the designer
      steroid Superdrol (methasteron): a case report and literature review.

PMID- 18720006
TI  - Decreased total antioxidant capacity in plasma, but not tissue, in experimental
      colitis.
AB  - The aim of the present work was to compare colonic mucosa and plasmatic oxidative
      stress measured concomitantly and with different degrees of injury in rats with
      colitis induced by trinitrobenzene sulfonic acid. Three groups were studied:
      control group, colitis group, and colitis exacerbated by diclofenac. Enzymatic
      markers of colon injury showed enhanced activity in both groups with colitis. The
      colitis group treated with diclofenac presented higher colonic damage score than
      the other groups. In both groups with colitis, higher values of tert butyl
      hydroperoxide-initiated-chemiluminescence and thiobarbituric acid-reactive
      substances in tissue and decreased total radical-trapping antioxidant potential
      (TRAP) levels in plasma were found. In conclusion, independently of the degree of
      colonic mucosa injury and inflammation, oxidative stress in tissue occurs as a
      consequence of pro-oxidants increase, and is not explained by a reduction of
      antioxidant defenses. In both conditions, TRAP determination decreases in plasma,
      but not in tissue.

PMID- 18720008
TI  - Detection of one-lung intubation incidents.
AB  - Lung sounds are very common source for monitoring and diagnosis of pulmonary
      function. This approach can be used for detecting one lung intubation (OLI)
      during anesthesia or intensive care. In this paper, an algorithm for detecting
      OLI from lung sounds is presented. The algorithm assumes a multiple-input
      multiple-output system, in which a multi-dimensional auto-regressive model
      relates the input (lungs) and the output (recorded sounds). An OLI detector is
      developed based on the generalized likelihood ratio test (GLRT), assuming
      coherent distributed sources for each lung. This method exhibited reliable
      results also when the lungs were modeled by incoherent distributed sources, which
      is a more accurate model for lung sources. The algorithm was tested using real
      breathing sounds recorded in an operating room, and it achieved an OLI detection
      rate of more than 95%, for each breathing cycle.

PMID- 18720007
TI  - A microstructurally motivated model of the mechanical behavior of tissue
      engineered blood vessels.
AB  - Mechanical models have potential to guide the development and use of engineered
      blood vessels as well as other engineered tissues. This paper presents a
      microstructurally motivated, pseudoelastic, mechanical model of the biaxial
      mechanics of engineered vessels in the physiologic pressure range. The model
      incorporates experimentally measured densities and alignments of engineered
      collagen. Specifically, these microstructural and associated mechanical inputs
      were measured directly from engineered blood vessels that were cultured over
      periods of 5-7.5 weeks. To the best of our knowledge, this is the first
      successful application of either a phenomenological or a microstructurally
      motivated mechanical model to engineered vascular tissues. Model development
      revealed the need to use novel theoretical configurations to describe the strain
      history of engineered vessels. The constitutive equations developed herein
      suggested that collagen remodeled between 5 and 7.5 weeks during a 7.5-week
      culture period. This remodeling led to strain energies for collagen that differed
      with alignment, which likely resulted from undulations that varied with
      alignment. Finally, biaxial data emphasized that axial extensions increase
      stresses in engineered vessels in the physiologic pressure range, thereby
      providing a guideline for surgical use: engineered vessels should be implanted at
      appropriate axial extension to minimize adverse stress responses.

PMID- 18720009
TI  - Non-traditional metabolic pathways of adrenal steroids.
AB  - Metabolic pathways are reconstructed from biochemical evidence to conceptualize
      the predominant route to important biomolecules. Pathways have heuristic value in
      their capacity to explain the metabolic derangements in genetic diseases of
      enzyme deficiencies and during pharmacologic inhibition of these enzymes.
      Implicit in the description of these pathways is the potential existence of
      alternate routes, variable order of reactions, and the inevitable by-products
      generated by incomplete efficiencies and competing enzymes. This chapter will
      consider alternate fates encountered by steroid hormone precursors in the adrenal
      gland, the variables influencing flux through these secondary pathways, and the
      significance of these diversions in health and disease.

PMID- 18720010
TI  - Neuron and gliocyte death induced by photodynamic treatment: signal processes and
      neuron-glial interactions.
AB  - The mechanisms of photodynamic (PD) damage to neurons and gliocytes are
      discussed. The spike reactions of neurons are described, with stimulation at high
      concentrations of photosensitizer and inhibition at low concentrations,
      accompanying necrosis. Glial cells developed both necrosis and apoptosis. Local
      laser inactivation of neurons increased light-induced apoptosis of gliocytes,
      i.e., neurons maintained gliocyte survival. Inter-and intracellular signaling
      plays an important role in the photolesioning of these cells. Studies using
      inhibitors and activators of signal proteins demonstrated the involvement of the
      Ca(2+)-dependent, adenylate cyclase, and tyrosine kinase pathways in the
      responses of neurons and gliocytes to PD treatment. Pharmacological modulation
      may alter the selectivity of PD neuron and gliocyte damage and the efficacy of PD
      treatment.

PMID- 18720011
TI  - Individual variability in the cytoarchitectonics of anterior limbic field 24 in
      the human brain.
AB  - The aim of the present work was to identify the main cytoarchitectonic
      characteristics of individual variability in anterior limbic field 24 in the left
      and right hemispheres of the human brain using state-of-the-art morphometric
      analysis methods. Computerized morphometric analysis was used to measure neuron
      profile areas in layers III and V of subfield 24c of the anterior limbic area of
      the cortex of the human brain, with assessment of the percentage composition of
      neurons in terms of this parameter, along with the total neuron fraction
      (proportion of microscope field occupied by neurons). These studies demonstrated
      significant individual variability in these characteristics, with asymmetry in
      the left and right hemispheres. Values for these parameters were large and had
      the greatest level of variability in associative layer III of the right
      hemisphere.

PMID- 18720012
TI  - The role of cutaneous afferents in controlling locomotion evoked by epidural
      stimulation of the spinal cord in decerebrate cats.
AB  - The effects of the cutaneous input on the formation of the locomotor pattern in
      conditions of epidural stimulation of the spinal cord in decerebrate cats were
      studied. Locomotor activity was induced by rhythmic stimulation of the dorsal
      surface of spinal cord segments L4-L5 at a frequency of 3-5 Hz. Electromyograms
      (EMG) recorded from the antagonist muscles quadriceps, semitendinosus, tibialis
      anterior, and gastrocnemius lateralis were recorded, along with the kinematics of
      stepping movements during locomotion on a moving treadmill and reflex responses
      to single stimuli. Changes in the pattern of reactions observed before and after
      exclusion of cutaneous receptors (infiltration of lidocaine solution at the base
      of the paw or irrigation of the paw pads with chlorothane solution) were
      assessed. This treatment led to impairment of the locomotor cycle: the paw was
      placed with the rear surface downward and was dragged along in the swing phase,
      and the duration of the stance phase decreased. Exclusion of cutaneous afferents
      suppressed the polysynaptic activity of the extensor muscles and the distal
      flexor muscle of the ipsilateral hindlimb during locomotion evoked by epidural
      stimulation of the spinal cord. The effects of exclusion of cutaneous afferents
      on the monosynaptic component of the EMG response were insignificant.

PMID- 18720013
TI  - Localization of human cortical areas activated on perception of ordered and
      chaotic images.
AB  - The aims of this study were to identify the locations of areas in the human
      cortex responsible for describing fragmented test images of different degrees of
      ordering and to identify the areas taking decisions regarding stimuli of this
      type. The locations of higher visual functions were determined by functional
      magnetic resonance imaging (fMRI) using a scanner fitted with a superconducting
      magnet and a field strength of 1.5 T. The blood oxygen level-dependent (BOLD)
      method was based on measurements of the level of hemoglobin oxygenation in the
      blood supplied to the brain. This level was taken to be proportional to the
      extent of neuron activation in the corresponding part of the gray matter. Stimuli
      were matrixes consisting of Gabor elements of different orientations. The measure
      of matrix ordering was the ratio of the number of Gabor elements with identical
      orientations to the total number of elements in the image. Brain neurons were
      activated by simultaneous changes in the orientations of all the elements,
      leading to substitution of one matrix by another. Substitution of the orientation
      was perceived by observers as rotation of the elements in the matrix. Stimulation
      by matrixes with a high level of ordering was found to activate the occipital
      areas of the cortex, V1 and V2 (BA17-BA18), while presentation of matrixes with
      random element orientations also activated the parietal-temporal cortex, V3, V4,
      V5 (BA19), and the parietal area (BA7). Brain zones responsible for taking
      decisions regarding the level of order or chaos in the organization of the
      stimuli are located in different but close areas of the prefrontal and frontal
      cortex of the brain, including BA6, BA9, and BA10. The results are assessed in
      terms of concepts of the roles and interactions of different areas of the human
      brain during recognition of fragmented images of different degrees of complexity.

PMID- 18720014
TI  - In memory of Billy R. Martin (1943-2008).

PMID- 18720015
TI  - Importance of small pores in microcrystalline cellulose for controlling water
      distribution during extrusion-spheronization.
AB  - The purpose of this research was to investigate the effects of particle size on
      the wet massing behavior of microcrystalline cellulose (MCC). In this study, a
      series of six fractionated MCC grades were customized and specially classified to
      yield different particle size varieties of the standard grade, Comprecel M101.
      All seven MCC grades were extensively characterized for the physical properties
      and wet massing behavior using mixer torque rheometry. Effects of MCC physical
      properties on the maximum torque (Torque(max)) were determined using partial
      least squares (PLS) analysis. Most physical properties varied systematically with
      particle size and morphological changes. Marked differences were observed in the
      small pore volumes (V (highP)) and BET surface areas of the MCC grades. Variables
      that exerted dominant influences on Torque(max) were identified. In particular,
      the significance of V (highP) in governing wet mass consistency was established.
      The role of V (highP) has not been reported in any study because this small but
      significant variation is likely to be obliterated or compensated by variation in
      other physical properties from MCC grades from different suppliers. The findings
      demonstrated the role of small pores in governing the wet mass consistency of MCC
      and provide a better understanding of MCC's superior performance as a
      spheronization aid by the ability to fulfill the function as a molecular sponge
      to facilitate pellet formation during wet granulation processes.

PMID- 18720016
TI  - Development and evaluation of lorazepam microemulsions for parenteral delivery.
AB  - The objective of this investigation was to develop lorazepam (LZM) microemulsions
      as an alternative to the conventional cosolvent based formulation. Solubility of
      LZM in various oils and Tween 80 was determined. The ternary diagram was plotted
      to identify area of microemulsion existence and a suitable composition was
      identified to achieve desired LZM concentration. The LZM microemulsions were
      evaluated for compatibility with parenteral fluids, globule size, in vitro
      hemolysis and stability of LZM. Capmul MCM demonstrated highest solubilizing
      potential for LZM and was used as an oily phase. LZM microemulsions were
      compatible with parenteral dilution fluids and exhibited mean globule size less
      than 200 nm. The in vitro hemolysis studies indicated that microemulsions were
      well tolerated by erythrocytes. The LZM microemulsions containing amino acids
      exhibited good physical and chemical stability when subjected to refrigeration
      for 6 months.

PMID- 18720018
TI  - Design of a watercourse and riparian strip monitoring system for environmental
      management.
AB  - Watercourses are complex ecosystems where numerous economic, ecological and
      heritage issues converge. To ensure their efficient management it is essential to
      have a full description of these multifunctional ecosystems and to know their
      evolution over time. This paper describes a method for monitoring watercourses
      and their riparian strips developed in Wallonia (southern Belgium). It is based
      on an inventory constructed by stratified random sampling comprising 1,071
      sampling plots distributed over a total length of 24,600 km of watercourses
      covered from their source. Each sampling plot is surveyed and measurements and
      fine observations are made on watercourse segments 50 m long. The method
      developed, which was applied on a regional scale, could easily be transposed to
      other entities, from large river basins, to an entire country. Examples of
      results obtained from a first inventory phase demonstrate the utility of this
      tool designed to supply qualitative and quantitative information to assist
      watercourse management.

PMID- 18720017
TI  - Assessment of biological and biochemical indicators in soil under transgenic Bt
      and non-Bt cotton crop in a sub-tropical environment.
AB  - There is concern that transgenic Bt-crops carry genes that could have undesirable
      effects on natural and agro-ecosystem functions. We investigated the effect of Bt
      cotton (expressing the Cry 1Ac protein) on several microbial and biochemical
      indicators in a sandy loam soil. Bt-cotton (MRC-6301Bt) and its non-transgenic
      near-isoline (MRC-6301) were grown in a net-house on a sandy clay loam soil. Soil
      and root samples were collected 60, 90, and 120 days after sowing. Soil from a
      control (no-crop) treatment was also included. Samples were analysed for
      microbial biomass C, N and P (MBC, MBN, MBP), total organic carbon (TOC), and
      several soil enzyme activities. The microbial quotient (MQ) was calculated as the
      ratio of MBC-to-TOC. The average of the three sampling events revealed a
      significant increase in MBC, MBN, MBP and MQ in the soil under Bt-cotton over the
      non-Bt isoline. The TOC was similar in Bt and non-Bt systems. Potential N
      mineralization, nitrification, nitrate reductase, and acid and alkaline
      phosphatase activities were all higher in the soil under Bt-cotton. Root dry
      weights were not different (P > 0.05), but root volume of Bt-cotton was higher on
      90 and 120 days than that of non-Bt cotton. The time of sampling strongly
      affected the above parameters, with most being highest on 90 days after sowing.
      We concluded from the data that there were some positive or no negative effects
      of Bt-cotton on the studied indicators, and therefore cultivation of Bt-cotton
      appears to be no risk to soil ecosystem functions.

PMID- 18720019
TI  - National assessment of sea level rise using topographic and census data for
      Turkish coastal zone.
AB  - Turkish coastal zone elevation to sea level rise was illustrated by using digital
      elevation model and Geographical information systems methods. It was intended to
      determine several parameters such as population, settlements, land use, wetlands,
      contribution to national agricultural production and taxes at risk by using high
      resolution SRTM topographic, orthorectified Landsat Thematic Mapper Mosaics and
      census data with GIS methods within 0-10 m elevation of national level. All
      parameters were examined for coastal cities, coastal districts, settlements and
      villages' status. As a result of the analysis of data set, it was found that
      approximately 7,319 km(2) of land area lies below 10 m contour line in Turkey,
      and is hence highly vulnerable to sea-level rise. 28 coastal cities, 191
      districts and 181 villages or towns are located below 10 m contour line in study
      area. In the short term, for the struggle of negative impact of sea level rise,
      the findings suggest that the Ministry of Environment should declare new areas as
      protection areas and develop special environmental programs for national level.

PMID- 18720020
TI  - Recent developments of certified reference materials for road transportation.
AB  - Chemical measurements often constitute the basis for informed decision-making at
      different levels in society; sound decision-making is possible only if the
      quality of the data used is uncompromised. To guarantee the reliability and
      comparability of analytical data an intricate system of quality-assurance
      measures has to be put into effect in a laboratory. Reference materials and, in
      particular, certified reference materials (CRMs) are essential for achieving
      traceability and comparability of measurement results between laboratories and
      over time. As in any other domain of analytical chemistry, techniques used to
      monitor the levels and fate of contaminants in the environment must be calibrated
      using appropriate calibration materials, and the methods must be properly
      validated using fit-for purpose matrix-matched CRMs, to ensure confidence in the
      data produced. A sufficiently large number of matrix CRMs are available for
      analysis of most elements, and the group of chemicals known as persistent organic
      pollutants, in environmental compartments and biota. The wide variety of
      analyte/level/matrix/matrix property combinations available from several
      suppliers enables analysts to select CRMs which sufficiently match the properties
      of the samples they analyse routinely. Certified reference materials are playing
      an increasing role in the monitoring of environmental pollution. This paper is an
      attempt for describing the recent development of certified reference materials
      for road transportation, which mainly covers the combustion of fossil fuel, road
      side dust etc.

PMID- 18720021
TI  - Comparative analysis of regional water quality in Canada using the Water Quality
      Index.
AB  - The Canadian Council of Ministers for the Environment (CCME) has developed a
      Water Quality Index (WQI) to simplify the reporting of complex water quality
      data. This science-based communication tool tests multi-variable water data
      against numeric water quality guidelines and/or objectives to produce a single
      unit-less number that represents overall water quality. The CCME WQI has been
      used to rate overall water quality in spatial and temporal comparisons of
      site(s). However, it has not been used in a comparative-analysis of exposure
      sites to reference sites downstream of point source discharges. This study
      evaluated the ability of the CCME WQI to differentiate water quality from metal
      mines across Canada at exposure sites from reference sites using two different
      types of numeric water quality objectives: (1) the water quality guidelines (WQG)
      for the protection of freshwater aquatic life and (2) water quality objectives
      determined using regional reference data termed Region-Specific Objectives (RSO).
      The application of WQG to the CCME WQI was found to be a good tool to assess
      absolute water quality as it relates to national water quality guidelines for the
      protection of aquatic life, but had more limited use when evaluating spatial
      changes in water quality downstream of point source discharges. The application
      of the RSO to the CCME WQI resulted in assessment of spatial changes in water
      quality downstream of point source discharges relative to upstream reference
      conditions.

PMID- 18720022
TI  - Expression of Sambucus nigra agglutinin (SNA-I') from elderberry bark in
      transgenic tobacco plants results in enhanced resistance to different insect
      species.
AB  - Tobacco plants (Nicotiana tabacum cv Samsun NN) have been transformed with the
      gene encoding the type-2 ribosome-inactivating protein (RIP) SNA-I' from
      elderberry (Sambucus nigra) under the control of the Cauliflower Mosaic Virus 35S
      promoter. Previous research confirmed that these plants synthesize, correctly
      process and assemble a fully active RIP. Variability in protein expression was
      observed within the transgenic lines. The effects of the type-2 RIP SNA-I'
      delivered through a leaf feeding assay were evaluated in the laboratory on two
      economically important pest insects belonging to the orders of Hemiptera, the
      tobacco aphid (Myzus nicotianae) and Lepidoptera, the beet armyworm (Spodoptera
      exigua). In the experiment with aphids, significant effects were observed on the
      life parameters, such as survival, intrinsic rate of increase, net reproductive
      rate, mean generation time and mean daily offspring, whereas with caterpillars
      significant reduction in fresh weight as well as retardation in development were
      observed. In addition, significant increases in mortality were noted for insects
      fed on the transgenic lines as compared to wild type plants. This information
      provides further support for RIPs having a role in plant resistance to insect
      pest species.

PMID- 18720023
TI  - Altered renal morphology in transgenic mice with cholecystokinin overexpression.
AB  - Although cholecystokinin is a regulatory peptide with a predominant role in the
      brain and the gastrointestinal tract, there is an increasing evidence for its
      role in the kidney. The aim of this study was to reveal morphological changes in
      the structure of kidney of mice with cholecystokinin overexpression by means of
      light, transmission and scanning electron microscope, and atomic force
      microscopy. Using immunohistochemistry the expression of important basement
      membrane proteins collagen IV, laminin and fibronectin, as well the distribution
      of cholecystokinin-8 in the renal structures was evaluated. The altered
      morphology of kidneys of mice with cholecystokinin overexpression was seen by all
      microscopic techniques used. The renal corpuscles were relatively small with
      narrow capsular lumen. The basement membranes of renal tubules were thickened and
      the epithelial cells were damaged, which was more pronounced for distal tubules.
      Characteristic feature was the increased number of vesicles seen throughout the
      epithelial cells of proximal and especially in distal tubules reflecting to the
      enhanced cellular degeneration. The relative expression of laminin but not
      collagen IV in the glomerular basement membrane was higher than in the tubular
      basement membranes. The content of fibronectin, in opposite, was higher in
      tubular membranes. Cholecystokinin-8 was clearly expressed in the glomeruli, in
      Bowman's capsule, in proximal and distal tubules, and in collecting ducts.
      Ultrastructural studies showed irregularly thickened glomerular basement
      membranes to which elongated cytopodia of differently shaped podocytes were
      attached. As foot processes were often fused the number of filtration pores was
      decreased. In conclusion, cholecystokinin plays important role in renal
      structural formation and in functioning as different aspects of urine production
      in mice with cholecystokinin overexpression are affected-the uneven glomerular
      basement membrane thickening, structural changes in podocytes and in filtration
      slits affect glomerular filtration, while damaged tubular epithelial cells and
      changed composition of thickened tubular basement membranes affect reabsorption.

PMID- 18720024
TI  - Natural selection and immortality.
AB  - Genomes replicate while the host cells reproduce. I explore the
      reproduction/replication dialogue, based on a deep analysis of bacterial genomes,
      in relation to ageing. Making young structures from aged ones implies creating
      information. I revisit Information Theory, showing that the laws of physics
      permit de novo creation of information, provided an energy-dependent process
      preserving functional entities makes room for entities accumulating information.
      I identify explicit functions involved in the process and characterise some of
      their genes. I suggest that the energy source necessary to establish reproduction
      while replication is temporarily stopped could be the ubiquitous polyphosphates.
      Finally, I show that rather than maintain and repair the original individual,
      organisms tend to metamorphose into young ones, sometimes totally, sometimes
      progressively. This permits living systems to accumulate information over
      generations, but has the drawback, in multicellular organisms, to open the door
      for immortalisation, leading to cancer.

PMID- 18720025
TI  - Transesterification activity of a novel lipase from Acinetobacter venetianus RAG
      1.
AB  - Transesterification activity and the industrial potential of a novel lipase
      prepared from Acinetobacter ventiatus RAG-1 were evaluated. Purified lipase
      samples were dialyzed against pH 9.0 buffer in a single optimization step prior
      to lyophilization. The enzyme and organic phase were pre-equilibrated
      (separately) to the same thermodynamic water activities (a (w)) ranging from a
      (w) 0.33 to 0.97. Production of 1-octyl butyrate by lipase-catalyzed
      transesterification of vinyl butyrate with 1-octanol in hexane was monitored by
      gas chromatography. Production of 1-octyl butyrate and initial rate of reaction
      depended on water activity. Product synthesis and rate of transesterification
      increased sharply with increase from a (w) 0.33 to 0.55. Highest product
      concentration (218 mM) and rate of reaction (18.7 micromol h(-1) . 10 microg
      protein) were measured at a (w) 0.86. Transesterification activity in hexane
      represented 32% of comparable hydrolytic activity in aqueous buffer.

PMID- 18720027
TI  - E/E': a prime number?

PMID- 18720028
TI  - Inflammation, heat shock proteins, and type 2 diabetes.
AB  - We propose that type 2 diabetes results from a vicious cycle of metabolically
      induced inflammation, impaired insulin responsiveness, and subsequent loss of
      homeostatic signaling. A crucial and previously under-recognized event
      contributing to this loss of homeostasis is a reduction in heat shock proteins
      (HSPs, or stress proteins). The central causal pathways of this cycle are the
      following: (a) obesity-driven inflammation promotes insulin resistance; (b)
      impaired insulin signaling in turn reduces the expression of HSPs, leaving
      tissues vulnerable to damage and allowing the accumulation of harmful proteins
      aggregates; and (c) resulting damage to the pancreatic beta-cell leads to further
      losses in insulin signaling, while a decline in anti-inflammatory HSPs allows
      inflammation to expand unhindered. Obesity and sedentary lifestyle perpetuate
      this cycle, while dieting and exercise forestall it by raising HSPs, reducing
      inflammation, and improving insulin signaling. Because HSP expression carries
      substantial metabolic costs, it is likely that an evolutionary history of high
      activity levels and resource scarcity selected for more conservative HSP
      expression than is appropriate for our current environment of caloric abundance.

PMID- 18720026
TI  - Protective dissipation of excess absorbed energy by photosynthetic apparatus of
      cyanobacteria: role of antenna terminal emitters.
AB  - Two mechanisms of photoprotective dissipation of the excessively absorbed energy
      by photosynthetic apparatus of cyanobacteria are described that divert energy
      from reaction centers. Energy dissipation, monitored as nonphotochemical
      fluorescence quenching, occurs at different steps of energy transfer within the
      phycobilisomes or core antenna of photosystem I. Although these mechanisms differ
      significantly, in both cases, energy dissipates mainly from terminal emitters:
      allophycocyanin B or core membrane linker protein (L(CM)) in phycobilisomes, or
      the longest-wavelength chlorophylls in photosystem I antenna. It is supposed that
      carotenoid-induced energy dissipation in phycobilisomes is triggered by light
      induced transformation of the nonquenched state of antenna into quenched state
      due to conformation changes caused by orange carotinoid-binding protein (OCP)
      phycobilisome interaction. Fluorescence of the longest-wavelength chlorophylls of
      photosystem I antenna is strongly quenched by P700 cation radical or by P700
      triplet state, dependent on redox state of the acceptor side cofactors of
      photosystem I.

PMID- 18720029
TI  - Characteristic imprint of single nucleotide polymorphisms in multiple sclerosis.
AB  - Although the main pathomechanism of multiple sclerosis (MS) is not known, an
      autoimmune response against the myelin basic proteins (MBPs) is presumed to be
      involved in its evolution and propagation. In this study, we examined whether the
      nucleotide sequences of the 3' untranslated regions (UTRs) of the DNAs encoding
      the MBP are characteristic of MS. These genetic regions are presumed to be
      responsible for the transport and localization of the mRNAs encoding the MBP in
      the glia cells, thereby influencing the building up of the myelin sheaths of the
      glia cells. The DNA region involving nucleotides 710-1540 of the UTRs of the MBPs
      was sequenced and analyzed in 52 relapsing-remitting MS patients, in 52
      neuroimaging alteration-free controls, and in 45 healthy volunteers. Although the
      examined UTRs exhibited a wide range of sequence variations in both the MS and
      the control subjects, we found a typical distribution of single nucleotide
      polymorphisms (SNPs) along the examined DNA sequence in the MS patients, which
      was different from that in the controls. We could distinguish two genetic
      regions: region A--nucleotide positions 851-896 and B--nucleotide positions 897
      1540, in the UTRs. Subjects with SNPs in region A but without SNPs in region B
      occurred significantly more frequently in the MS group than in the control group
      (30.8% versus 3.85%, p < 0.0002848, OR 11.11, 95% CI--2.4-51.4, p < 0.0004). The
      distribution pattern of the SNPs in the UTRs seems to be highly characteristic of
      relapsing-remitting MS. These findings call attention to the possible roles of
      the UTRs of the MBPs in the development of MS.

PMID- 18720030
TI  - Does single embryo transfer improve the obstetric and neonatal outcome of
      singleton pregnancy?
AB  - Singleton pregnancies following in vitro fertilization (IVF) and intracytoplasmic
      sperm injection (ICSI) are associated with increased risks of abnormal
      placentation, pre-eclampsia and preterm birth. These risks might partly be a
      consequence of the number of transferred embryos. In this commentary we summarize
      the results of three observational studies and one randomized study with 1052
      pregnancies following single embryo transfer (SET). An increased age- and parity
      adjusted risk of gestational hypertension and placenta previa in the SET
      pregnancies as compared to the spontaneously conceiving controls was reported in
      one of the studies. Preterm births occurred in 6-12% of SET pregnancies and 4-6%
      of the newborns were of low birth weight (LBW). The frequency of preterm birth
      and LBW after SET were considered either lower than or similar to those after
      double embryo transfer (DET) but higher than after spontaneous conception.
      Comparison of SET and DET pregnancies thus shows heterogeneous results. Still, it
      seems that not even a transfer of one good-quality embryo at a time diminishes
      all the previously identified increased risks of certain obstetric complications
      and preterm births in singleton pregnancies following IVF or ICSI.

PMID- 18720031
TI  - Vulvodynia. Definition, diagnosis and treatment.
AB  - Vulvodynia is a chronic painful disorder with an estimated prevalence of 9-12%. A
      rising incidence of the condition constitutes a growing problem. This has lead to
      an increased focus on etiology and treatment, while the definition also requires
      attention. Previous assumptions stating that the problem is solely a
      psychological disorder have been abandoned, because inflammatory mechanisms and
      genetic factors have been found to be involved in the pathogenesis as well as
      psychosexual contributors. This article describes the terminology and definition
      of the condition, theories on patho-physiological mechanisms underlying the
      disorder, methods of diagnosis and evidence and recommendations on clinical
      management. A critical examination of the literature regarding vulvodynia reveals
      numerous strategies and recommendations for treatment, many of which are not
      evidence-based, and a lack of effective treatment for all patients. Research is
      being undertaken internationally to find more specific and unequivocal causes of
      the disorder, as well as to develop evidence-based methods of treatment.

PMID- 18720032
TI  - Glassy cell carcinoma arising in the vagina.
AB  - Glassy cell carcinoma is a rare neoplasm that occurs most frequently in the
      uterine cervix. We describe the first reported case of glassy cell carcinoma
      arising in the vagina. A 77-year-old Japanese woman was admitted to our hospital
      for atypical genital bleeding. Gynecological examination revealed a macroscopic
      vaginal cancer of 1.5 cm in diameter located in the upper 1/3 of the vagina. The
      pathological diagnosis of the biopsied specimen was glassy cell carcinoma. She
      was successfully treated by conventional radiation therapy and chemotherapy under
      the diagnosis of stage I vaginal cancer (International Federation of
      Gynecologists and Obstetricians classification, 1986). The patient is alive,
      without evidence of recurrence, 21 months following the radiation therapy. Glassy
      cell carcinoma is classified as the most poorly differentiated form of
      adenosquamous carcinoma. The present case illustrates the potential for glassy
      cell carcinoma to arise in the Mullerian epithelium throughout the female genital
      tract.

PMID- 18720033
TI  - Association between lactate concentration in amniotic fluid and dysfunctional
      labor.
AB  - OBJECTIVES: To assess whether there is an association between high lactate
      concentration in amniotic fluid (AF) and labor dystocia. DESIGN: Prospective
      observational study. SETTING: Labor ward at General South Hospital, Stockholm,
      Sweden. POPULATION AND METHODS: Women in active labor attending labor ward,
      having at least two consecutive measurements of lactate concentration in AF,
      measured 60 minutes apart. MAIN OUTCOME MEASURE: Dysfunctional labor, defined as
      instrumental or operative delivery due to dystocia. RESULTS: Among women with
      spontaneous vaginal deliveries (n=23) the mean lactate concentration in AF during
      labor was 8.9 mmol/l (range 6.6-10.8), and among women with operative delivery
      due to labor dystocia (n=31) the corresponding value was 10.9 mmol/l (range 8.0
      16.1) (p<0.001). Of 29 women with a high lactate concentration (> or =10.1
      mmol/l) in at least two consecutive measures collected at least 60 minutes apart,
      25 (86%) were delivered instrumentally/operatively due to dystocia. Using this
      definition of a positive test, the diagnostic accuracy to predict operative
      delivery due to dystocia was: sensitivity 81% (25/31), specificity 83% (19/23),
      positive predictive value 86% (25/29), and negative predictive value 76% (19/25).
      The likelihood ratio was 5.0 for a positive test and 0.2 for a negative test.
      CONCLUSIONS: High lactate concentration (> or =10.1mmol/l) in at least two
      consecutive samples of AF collected during labor 60 minutes apart is strongly
      associated with dystocia. This method might be useful in clinical management to
      identify labor dystocia at an early stage of labor.

PMID- 18720034
TI  - Maternal fatalities, fetal and neonatal deaths related to motor vehicle crashes
      during pregnancy: a national population-based study.
AB  - OBJECTIVES: Firstly, determine the mortality rate for: pregnant women; fetuses
      and neonates, due to motor vehicle crashes (MVCs) during pregnancy; and secondly,
      the rate of major injuries among pregnant women and the rate of involvement of
      pregnant women in crashes. DESIGN: A national population-based, retrospective
      descriptive study. SETTING: Sweden, 1991-2001. Population. All pregnant and non
      pregnant women age 15-44. METHODS: Linkage of national traffic, medical and
      autopsy registers. MAIN OUTCOME MEASURES: Maternal death or injury and
      corresponding fetal death. Results. MVCs during pregnancy caused 1.4 maternal
      fatalities per 100,000 pregnancies and a fetus/neonate mortality rate of least
      3.7 per 100,000 pregnancies. The incidence of maternal major injury was
      23/100,000 pregnancies and crash involvement was 207/100,000 pregnancies.
      CONCLUSIONS: MVCs during pregnancy were a significant cause of maternal
      fatalities, fetal and neonatal deaths, responsible for almost 1/3 of all maternal
      deaths and fatalities, and caused nearly three times more fetal plus neonatal
      deaths than maternal fatalities.

PMID- 18720035
TI  - Factors associated with symptoms of pelvic floor dysfunction six years after
      primary operation of genital prolapse.
AB  - OBJECTIVE: To determine prevalence of pelvic floor dysfunction (PFD) symptoms in
      women six years after primary pelvic organ prolapse (POP) surgery and analyze
      predictive factors for these symptoms. DESIGN: Cross-sectional observational
      study. SETTING: Three Swedish hospitals. SAMPLE: Women who underwent primary POP
      surgery in 1993 and had no subsequent POP surgery during the following six years.
      METHODS: Clinical data from patient records and a postal questionnaire concerning
      symptoms of PFD completed in 1999. MAIN OUTCOME MEASURES: Prevalence of PFD
      symptoms, predictive factors. RESULTS: Urinary incontinence episodes > or =weekly
      were reported by 41%, feeling of vaginal bulging by 18% and solid stool
      incontinence by 15%. Thirty nine percent were sexually active; 15% refrained
      completely from sexual activity because of own discomfort or pain and 46% had no
      sexual activity due to lack of or sick partner. Discomfort or pain during sexual
      activity was experienced by 42%. Previous incontinence surgery and urinary
      incontinence prior to POP surgery were predictive factors for urinary
      incontinence. Anterior repair was protective for the postoperative symptoms of
      incomplete bladder and bowel emptying and vaginal bulging. Posterior repair was a
      risk factor for incomplete bowel emptying and solid stool incontinence. The
      association between posterior repair and discomfort or pain during sexual
      activity was not significant. CONCLUSION: The prevalence of PFD symptoms six
      years after primary POP surgery seemed high. The extent of POP surgery was
      predictive for postoperative symptoms of urinary and bowel dysfunction but not
      for discomfort or pain during sexual activity.

PMID- 18720036
TI  - Diagnosis and prediction of parental origin of triploidies by fetal nuchal
      translucency and maternal serum free beta-hCG and PAPP-A at 11-14 weeks of
      gestation.
AB  - The study objective was to determine the parental origin of triploidy in relation
      to findings from early risk assessment in a combined screening program between
      2004 and the end of 2006. Triploidy was diagnosed in six chorion villus samples
      and two samples from missed abortions. After informed consent, quantitative
      fluorescence polymerase chain reaction analysis was performed on the five cases
      where we received blood from both parents and tissue from fetuses. In four cases
      the origin of the triploidy was paternal and in one maternal, in accordance with
      previous findings in type I and type II triploidies. Finding triploidy is
      possible by risk assessment (ultrasound and double test), and thereby women may
      have the opportunity for early termination of pregnancy.

PMID- 18720037
TI  - IVF pregnancies: neonatal outcomes after the new Italian law on assisted
      reproduction technology (law 40/2004).
AB  - OBJECTIVE: To compare maternal and neonatal outcome of pregnancies achieved by
      assisted reproduction technique (ART) according to the guidelines of the newly
      established Italian ART law 40/2004, with that of naturally conceived. DESIGN:
      Three hundred and sixty-four ART pregnancies and 304 naturally conceived
      pregnancies were analyzed in terms of the incidence of obstetric complications
      and perinatal outcome. Control group was enrolled prospectively after being
      matched for an extensive number of maternal characteristics. RESULTS: Among
      singletons, ART pregnancies when compared to naturally conceived pregnancies
      showed a higher incidence of pregnancy loss (23.4% versus 10.5%) and a lower mean
      birth weight. A higher but not significant incidence of small for gestational age
      fetuses was observed in ART pregnancies, compared to those from normally
      conceived pregnancies (7.2% versus 2.7%). Moreover, the ART pregnancies showed a
      slightly, but nonetheless significantly shorter mean gestational age (38.6 versus
      39.3 weeks) and more frequent preterm deliveries (11%) than the control group
      (2.7%). No difference was found in terms of other obstetric complications such as
      pregnancy-induced hypertension, gestational diabetes and placental abruption.
      Neonatal outcome was similar in both groups. CONCLUSION: Although the obstetric
      outcome among singleton ART pregnancies was good, these patients should be
      considered obstetric risk cases. The different frequency of complications is not
      related to maternal age or parity and could be the consequence of infertility or
      the procedures by which these women conceived. The reasons are, however, unclear
      and further studies are necessary.

PMID- 18720038
TI  - Prepregnancy weight status and the risk of adverse pregnancy outcome.
AB  - OBJECTIVE: To examine the association between maternal pre-pregnancy weight
      status and the risk of stillbirth, pre-eclampsia and preterm delivery. DESIGN:
      Hospital-based cohort study using prospectively recorded data. SETTING: Ten
      public hospitals in Buenos Aires, Argentina. POPULATION: 46,964 pregnant women
      who had a delivery during 2003-2006. METHODS: Prepregnancy body mass index (BMI)
      was used to categorize women in four weight categories from underweight to obese.
      The reference group were women with BMI between 18.5 and 24.9. Crude and adjusted
      odds ratios were calculated using multiple logistic regression analysis. MAIN
      OUTCOME: Preterm birth, pre-eclampsia and stillbirth. RESULTS: The risk of
      preterm delivery decreased with increasing BMI, with the highest risk among
      underweight women (OR: 1.45; 95% CI: 1.26-1.67), and the lowest risk among the
      overweight. The risk of pre-eclampsia was highest among overweight (OR: 1.55;
      95%CI: 1.30-1.86) and obese women (OR: 3.10; 95%CI: 2.54-3.78). Obese or
      overweight women did not have an increased risk of stillbirth in this study.
      CONCLUSIONS: Overweight and obese women have an increased risk for pre-eclampsia,
      while underweight women have an increased risk for preterm delivery. There is a
      high prevalence of overweight women in the obstetric population in Buenos Aires.

PMID- 18720039
TI  - Rapid prenatal diagnosis of spinal muscular atrophy by denaturing high
      performance liquid chromatography system.
AB  - OBJECTIVE: Use of Denaturing High-Performance Liquid Chromatography (DHPLC) in
      prenatal diagnosis of spinal muscular atrophy (SMA). METHODS: Thirty-three
      members of 7 families participated in carrier test and disease detection of SMA.
      Prenatal genetic diagnosis was performed if both parents were carriers or any
      family members had SMA. DNA extracted from blood, chorionic villi and amniotic
      fluid was amplified and used for DHPLC. RESULTS: Twenty SMA carriers, seven SMA
      affected cases, and six normal individuals were identified. SMA status was
      demonstrated by genotyping and total copy number determinations of SMN1 and SMN2.
      Families 1-3 were classified as group one (SMA affecting previously born child).
      Group two, comprising families 4 and 5, had lost a child due to an unknown
      muscular disease. Group three (SMA-affected parent) comprised families 6 and 7;
      carrier testing was done. DHPLC prenatal genetic diagnosis was made in seven
      pregnancies, one in each family (affected, n=2; carrier, n=3; normal, n=2).
      Pregnancy was terminated for the two affected fetuses. The others were delivered
      uneventfully and SMA free. CONCLUSION: DHPLC prenatal diagnosis of SMA and
      determination of SMA status in adults is possible, and SMN1 and SMN2 copy numbers
      can be determined.

PMID- 18720040
TI  - Complications and patient satisfaction after transobturator anterior and/or
      posterior tension-free vaginal polypropylene mesh for pelvic organ prolapse.
AB  - Complications and satisfaction with anterior and/or posterior prolapse repair
      using a transobturator polypropylene mesh (Prolift) in a single center
      prospective cohort was assessed. Among 30 women six mesh erosions were noted,
      five (17%) after anterior and one (3%) with combined anterior and posterior
      procedures. The patients' impression after six months was 'better' to 'much
      better' in 25 (84%), no change in four (13%) and one was worse (3%). At six
      months one patient had suffered re-appearance of an anterior prolapse and one had
      relapse of both an anterior and posterior prolapse. Concomitant procedures were
      not significantly related to risk of erosion, but the erosion group was younger
      (mean age 58 vs. 67 years, p<0.0001). After polypropylene transobturator mesh for
      pelvic organ prolapse relapses do occur. Safety may be hampered by a high rate of
      mesh erosions.

PMID- 18720041
TI  - Improved accuracy of postpartum blood loss estimation as assessed by simulation.
AB  - OBJECTIVE: Caregivers underestimate the amount of blood loss, but this almost
      five decades-old assumption has not been validated. We aimed at assessing the
      accuracy of estimated blood loss by obstetrical teams during a simulated
      Postpartum hemorrhage (PPH) scenario. STUDY DESIGN: a prospective study conducted
      as part of the simulation-based training course, using sophisticated mannequin
      simulators adapted for obstetrical training by specially designed devices.
      SETTING: Part of the simulation-based training course. POPULATION: Obstetrical
      teams consisted of physicians and obstetrical nurses. METHODS: Each of the
      participating obstetrical teams assessed blood loss during PPH scenarios. Their
      estimates were compared to the actual predefined 3.5-liter blood loss. An
      intervention group underwent a similar course in which they recorded their
      estimations after 1, 2 and 3.5 liters were lost. OUTCOME MEASURES: Blood loss
      estimates after completion of the scenario in both groups. RESULTS: Fifty
      obstetrical teams took part in the study. Eight comprised the interventional
      group. The average estimated blood loss was 1,780 ml (49% underestimation) for
      non-interventional teams. The interventional groups estimated blood loss to be
      2,400 ml (32% underestimation). The main method of estimating blood loss was 'gut
      feeling', followed by verbalized guesses of team members and assessments of the
      'patient's' hemodynamic status. CONCLUSIONS: Accuracy of blood loss estimations
      by a simulation-based PPH scenario was 50-60%. Measurements at predetermined
      intervals significantly improved accuracy of these estimations. Our study
      suggests that implementation of periodic estimations of blood loss in the
      management of PPH might improve clinical judgment.

PMID- 18720042
TI  - Regulation of ovarian UT-OC-2 carcinoma cells by cytokines: effects on cell
      proliferation, activation of transcription factors and apoptosis.
AB  - BACKGROUND: It is known that immunologic factors are involved in the regulation
      of the growth of ovarian carcinoma and that granulocytes are often found on the
      site of ovarian cancer. Therefore, we chose to investigate the effects of
      cytokines on UT-OC-2 ovarian endometrioid adenocarcinoma cells in vitro. In order
      to investigate the molecular mechanisms involved, the activation of two key DNA
      binding proteins, AP-1 and transcription factor NF-kappaB (NF-kappaB), was
      studied. Since DNA extracted from the UT-OC-2 cells showed fragmentation typical
      of apoptosis, we also studied the effects of cytokines on this event. METHODS:
      The effects of the studied cytokines on the proliferation of UT-OC-2 cells were
      investigated by (125)I-deoxyuridine incorporation. The activation of DNA-binding
      proteins was studied by electrophoretic mobility shift assay. Statistical
      analyses were performed by Student's t-test. RESULTS: Interferon alpha (IFN
      alpha), transforming growth factor beta(1) (TGF-beta(1)), tumor necrosis factor
      alpha (TNF-alpha) and interferon gamma (IFN-gamma) all had a significant
      inhibitory effect on cell proliferation. Granulocyte colony stimulating factor
      (GM-CSF) did not alter cell proliferation significantly. Transcription factors AP
      1 and NF-kappaB were both found to be constitutively active in UT-OC-2 ovarian
      carcinoma cells. We were able to show that IFN-gamma, TGF-beta(1) and TNF-alpha
      all increased the binding activity of transcription factor AP-1 (AP-1). The
      binding activity of transcription factor NF-kappaB was not altered by any of the
      cytokines studied, with the exception of IFN-gamma. IFN-gamma had also a clear
      inhibitory effect on the apparent magnitude of apoptosis, whereas TNF-alpha and
      TGF-beta(1) showed no effect. CONCLUSION: The results of this study show that TNF
      alpha, TGF-beta(1), and IFN-gamma are able to inhibit the proliferation of UT-OC
      2 ovarian carcinoma cells. Activation of AP-1 seems to be involved in the growth
      regulating processes induced by IFN-gamma, TGF-beta(1) and TNF-alpha; IFN-gamma
      is also able to increase the binding activity of NF-kappaB and inhibited
      apoptosis in ovarian cancer cells.

PMID- 18720043
TI  - Clinicopathological significance of circadian rhythm-related gene expression
      levels in patients with epithelial ovarian cancer.
AB  - OBJECTIVE: Recent studies implicate circadian genes in the regulation of cell
      cycle, apoptosis, and cell proliferation at a molecular level. These genesey
      affect cancer incidence, prognosis, and chemosensitivity. In this study, we
      measured the expression levels of clock genes and correlated their expression
      levels with clinicopathological parameters in epithelial ovarian cancer. METHODS:
      The expression levels of core clock genes, per1, per2, per3, cry1, cry2, Bmal1,
      clock, and CKIepsilon were quantified by real-time quantitative Reverse
      transcription-polymerase chain reaction in 83 ovarian cancer tissues and 11
      normal ovarian tissues. RESULTS: The expression levels of per1, per2, cry2,
      clock, CKIepsilon in ovarian cancers were significantly lower than those in
      normal ovaries. In contrast, cry1 expression was highest among the eight examined
      clock genes, followed by per3 and Bmal1. Cry1 expression was much higher in
      cancer than that in normal ovaries. Localized circadian gene expression was
      determined in cancer cells by in situ hybridization analysis. Cry1 expression was
      significantly reduced in mucinous and grade 3 tumors. Bmal1 expression was also
      significantly reduced in mucinous adenocarcinomas as compared to other
      histologies. In a multivariate analysis, the combination of low cry1 expression
      and low Bmal1 expression was an independent prognostic factor, as well as stage
      and histological subtype. CONCLUSIONS: The antiphase expression of cry1 and Bmal1
      may be preserved in ovarian cancers. The combination of cry1 and Bmal1 expression
      might become a possible prognostic marker in epithelial ovarian cancer.

PMID- 18720044
TI  - A 12-week randomised study comparing intravenous iron sucrose versus oral ferrous
      sulphate for treatment of postpartum anemia.
AB  - OBJECTIVE: To analyze the effect of intravenous ferrous sucrose compared with
      oral ferrous sulphate on hematological parameters and quality of life in women
      with postpartum anemia. DESIGN: Open randomised controlled trial. SETTING:
      Multicentre study comprising five obstetrical departments in Norway. POPULATION:
      Hundred and twenty-eight postpartum women with hemorrhagic anemia (Hb between 6.5
      g/100 ml and 8.5 g/100 ml). The intervention group (59 women) received 600 mg
      iron sucrose intravenously followed by 200 mg iron sulphate daily from week 5.
      The control group (70 women) were given 200 mg iron sulphate daily. METHODS:
      Randomisation and start of treatment occurred within 48 hours of the delivery.
      Participants were followed up at 4, 8 and 12 weeks. MAIN OUTCOME MEASURES:
      Hemoglobin, ferritin and quality of life assessed with the Medical Outcomes Study
      Short Form 36 (SF-36) and the Fatigue Scale. RESULTS: After 4 weeks the mean
      hemoglobin values in both groups were similar (11.9 g/100ml vs. 12.3g/100ml,
      p=0.89). The mean serum ferritin value after 4 weeks was significantly higher in
      the intervention group with 13.7 microg/L vs. 4.2 microg/L in the control group
      (p<0.001). At 8 and 12 weeks the hematological parameters were similar. The total
      fatigue score was significantly improved in the intervention group at week 4, 8
      and 12, whereas SF-36 scores did not differ. CONCLUSION: Women who received 600
      mg intravenous iron sucrose followed by standard oral iron after four weeks,
      replenished their iron stores more rapidly and had a more favorable development
      of the fatigue score indicating improved quality of life.

PMID- 18720045
TI  - Adhesion molecules (VCAM-1 and ICAM-1) and C-reactive protein in women with
      history of preeclampsia.
AB  - Several studies suggest that women with previous preeclampsia (PE) are at
      increased risk of cardiovascular disease (CVD). We examined circulating
      concentrations of adhesion molecules and C-reactive protein (CRP), markers for
      endothelial and inflammatory reactions, in addition to blood pressure and
      anthropometric measurements in 58 women with a history of PE and 49 control women
      with no pathology associated to pregnancy. Soluble adhesion molecules were
      measured by standard commercial ELISA methods and plasma CRP levels by automated
      enzymatic assays. Systolic and diastolic blood pressures and waist-to-hip ratios
      were significantly higher in women with history of PE than in control group.
      There were no significant differences in circulating levels of sICAM-1, sVCAM-1
      and CRP in the study population. Women with a history of PE do not have a
      persistent inflammatory state that could induce overexpression of these
      molecules, which was supported by normal levels of CRP. The study supports the
      existence of common risk factors for PE and CVD, namely obesity and hypertension.

PMID- 18720046
TI  - Maternal eating disorders influence sex ratio at birth.
AB  - We explored sex ratio at birth, defined as the proportion of male live births, in
      women with anorexia nervosa, bulimia nervosa, binge eating disorder, and eating
      disorders not otherwise specified-purging type (EDNOS-P) relative to a referent
      group in a large population-based sample of 38,340 pregnant women in Norway.
      Poisson regressions were adjusted for mother's age, pre-pregnancy BMI, lifetime
      smoking status, maternal education, income, marital status, gestational age, and
      parity. Lower proportions of male live births were observed in the anorexia and
      bulimia groups, while binge eating disorder and EDNOS-P were associated with a
      higher proportion of male births. These data suggest that maternal eating
      disorders may influence offspring sex and that the direction of effect may vary
      by eating disorder subtype. If confirmed, this finding could provide evidence in
      formulating hypotheses regarding the consequences of eating disorders and
      determinants of sex ratio at birth.

PMID- 18720047
TI  - Postpartum oral health parameters in women with preterm birth.
AB  - OBJECTIVE: It has been suggested that poor oral health and periodontal disease,
      in particular, associate with adverse birth outcomes. However, previous reports
      on the topic are conflicting. The objective of the present cross-sectional study
      was therefore to compare the oral health parameters of a racially and socio
      economically homogeneous group of women who gave birth before 259 gestational
      days (37 weeks) with those of women who went full-term. MATERIAL AND METHODS: We
      studied various dental parameters, including prevalence of dental caries,
      gingival bleeding on probing, the probing periodontal pocket depths, and the
      carriage of periodontal pathogens in 328 all-Caucasian women with singleton
      births. Seventy-seven of the women had preterm births, while 251 had full-term.
      Dental data were recorded within 2 days postpartum and analyzed with data from
      medical history, prenatal care, and delivery records. RESULTS: Preterm mothers
      had more dental caries (93.5%) than full-term mothers (85.3%) when assessed as
      carious teeth in the mouth (p=0.06). In clinical and microbiological periodontal
      health parameters, however, no differences could be seen between the preterm and
      full-term mothers. Primiparity, low weight-gain, and antimicrobial drug use
      during pregnancy were the significant predictors for preterm birth. CONCLUSIONS:
      Although we cannot make any causal linkage, the oral health parameters were no
      different in women who experienced preterm births compared with those who had
      full-term births in this cohort. Only established systemic risk factors explained
      the preterm birth.

PMID- 18720048
TI  - Developmental stages of permanent canines, premolars, and 2nd molars in 244
      Danish children.
AB  - OBJECTIVE: The purpose of this study was to establish reference values for
      maturity of permanent canines, premolars, and permanent 2nd molars in Danish
      children, and to focus on differences between the right and left sides, males and
      females, and the maxilla and mandible. MATERIAL AND METHODS: Panoramic
      radiographs from 106 males (8-14 years) and 137 females (7 years 2 months to 13
      years 8 months) were analyzed, along with the maturity of the canines, premolars,
      and 2nd molars in each radiograph. Each tooth was categorized according to
      Haavikko's crown and root morphology. Inter-observer reliability was performed.
      For statistical analysis, Bowker's test was used for symmetry evaluation and
      comparison of maturity in the maxilla and mandible. The association between stage
      and age was presented by cumulative distributions. The Wilcoxon rank sum test was
      used for evaluating differences between genders. RESULTS: Differences in maturity
      between the left and right sides were non-significant. A significant difference
      in dental maturity was observed between males and females, except for the
      maxillary 2nd premolar. Females matured earlier than males. The mandibular
      canines matured significantly earlier than the maxillary canines in females. No
      significant differences between the jaws were observed in the maturation of the
      premolars and 2nd molars. CONCLUSION: These reference values for dental maturity
      can be useful in orthodontic treatment planning and as a reference for
      odontological forensic age determination.

PMID- 18720049
TI  - Cost-analysis of school-based fluoride varnish and fluoride rinsing programs.
AB  - OBJECTIVE: From a dental care perspective, we analyze whether the prevention of
      approximal caries by fluoride varnish treatment (FVT) or by fluoride mouth
      rinsing (FMR) could contain costs in an extended period of follow-up after the
      end of school-based prevention programs. MATERIAL AND METHODS: It is assumed in a
      model that, after 3 years of prevention with either FVT or FMR according to
      published studies, the "natural course" of approximal caries progression would
      follow for 5 consecutive years, as described in a Swedish longitudinal study. The
      outcome and costs of FVT, FMR and controls were modelled from years 4 to 8.
      RESULTS: The FVT program had a better outcome in reducing approximal caries than
      FMR, and costs were lower. The FVT was expected to result in cost containment
      compared to controls 3 years after the end of the preventive FVT program. The
      ratio benefits to costs were 1.8: 1 for FVT and 0.9: 1 for FMR. CONCLUSIONS:
      Prevention of approximal caries by FVT may result in cost containment, at a
      benefit cost ratio of 1.8: 1, given that the program can be administered at
      school.

PMID- 18720050
TI  - Utilization of toothpaste and fluoride content in toothpaste manufactured in
      Tanzania.
AB  - OBJECTIVE: To determine the use of toothpaste, the reasons behind its irregular
      use, the cost perceptions, and the fluoride concentrations in locally
      manufactured toothpaste. MATERIAL AND METHODS: A total of 978 dental patients
      attending 13 dental clinics for 2 weeks in June 2007 completed a pre-tested
      questionnaire on toothpaste use. Toothpaste was collected from shops in Dar es
      Salaam and analyzed at the laboratory of the Dental School in Amsterdam. Logistic
      regression was applied to determine the relative importance of independent
      variables on usage and perceptions about the cost of toothpaste. RESULTS: Eighty
      six percent of respondents used toothpaste daily. Of the 130 who used toothpaste
      less than once a day, 57.7% gave financial reasons for their irregular use.
      Toothpaste was perceived as expensive by 34.8% of respondents. Urban residents
      were five times more likely than rural residents to use toothpaste. Younger
      respondents were more likely than older respondents: to perceive toothpaste as
      important, to brush their teeth, to use toothpaste, and to brush their teeth
      regularly. All toothpaste manufactured in Tanzania had free fluoride
      concentrations below 400 ppm. CONCLUSIONS: Most respondents used toothpaste
      regularly and one-third regarded it as expensive. Toothpaste manufactured in
      Tanzania had free fluoride concentrations below the optimum levels for dental
      caries prevention. For a well-functioning Basic Package of Oral Care, the
      authority responsible for oral health has to take measures aimed at lowering the
      price of toothpaste, and toothpaste manufacturers have to ensure that their
      products have the optimal fluoride concentration for dental caries prevention.

PMID- 18720051
TI  - Osteoclast differentiation during experimental tooth movement by a short-term
      force application: an immunohistochemical study in rats.
AB  - OBJECTIVE: The origin of osteoclasts responsible for bone resorption during
      orthodontic tooth movement is not yet clear. Their precursors may reside within
      the periodontal ligament (PDL) or could be recruited from the circulation or the
      bone marrow. The aim of this study was to investigate the spatial and sequential
      distribution of osteoclast precursors during experimental tooth movement by using
      three differentiation markers: receptor for macrophage colony stimulating factor
      (c-Fms), receptor activator of nuclear factor-kappaB (RANK), and calcitonin
      receptor (CTR). MATERIAL AND METHODS: Six-week-old Wistar rats were used. Elastic
      bands were inserted between the upper 1st and 2nd molars for 1, 2, 3, and 6 days.
      Immunohistochemical staining for c-Fms, RANK, or CTR was performed on
      parasagittal sections and positive cells were counted. RESULTS: Before force
      application, many c-Fms+ and a few RANK+ precursors were present in the bone
      marrow. No c-Fms+ osteoclast precursors were observed in the PDL. After force
      application, the number of RANK+ but not c-Fms+ precursors increased rapidly in
      the PDL. In bone marrow, the number of c-Fms+ and RANK+ precursors also increased
      rapidly, as did multinuclear c-Fms+, RANK+, and CTR+ cells. Subsequently, the
      number of c-Fms+, RANK+, and CTR+ multinuclear cells in the PDL increased. After
      6 days, the expression profiles tended to return to baseline levels. CONCLUSION:
      Osteoclast precursors differentiate within the bone marrow and then migrate into
      the PDL during early tooth movement.

PMID- 18720052
TI  - Dental status and oral function in an adult group of subjects with thalidomide
      embryopathy - a clinical and questionnaire study.
AB  - OBJECTIVE: The purpose of the study was to present the results of an oral
      examination of individuals with thalidomide embryopathy in relation to dental
      conditions and functional aspects of the masticatory system, with a special focus
      on tooth wear. MATERIAL AND METHODS: All 108 subjects with thalidomide
      embryopathy living in Sweden were invited to participate in a comprehensive
      investigation, and approximately one-third, 31 subjects (13 F and 18 M, aged 45
      49 years), took part. The methods included a questionnaire and clinical and
      radiographic examinations. RESULTS: Most of the subjects had regular dental care,
      which they in general considered sufficient. All except one always brushed their
      teeth themselves. One subject had limited mouth opening (25 mm). There were no
      great deviations from normal anatomy and function of the masticatory system.
      Caries and periodontal conditions were also normal. Regurgitation was reported by
      42% of the subjects. Tooth wear was more extensive than in comparable age groups.
      About a third of the subjects had Class III or edge-to-edge occlusion.
      CONCLUSIONS: In general, subjects with thalidomide embryopathy had no great
      deviations in dental conditions from people of the same age in the general
      population except for an increased rate of tooth wear and a higher prevalence of
      prenormal jaw relations. Tooth wear was related less to use of the teeth as tools
      and more to dental erosion associated, among other things, with a high rate of
      regurgitation.

PMID- 18720053
TI  - Substantivity of amine fluoride/stannous fluoride following different modes of
      application: a randomized, investigator-blind, placebo-controlled trial.
AB  - OBJECTIVE: Amine fluoride/stannous fluoride (ASF) is proven to be effective
      against plaque and gingivitis. The purpose of this clinical controlled study was
      to investigate the influence of different application modes on the substantivity
      of this formulation. MATERIAL AND METHODS: Seventeen healthy volunteers received
      a professional dental prophylaxis. Undisturbed plaque growth was permitted for
      the next 48 h. In a crossover design, participants received ASF as a single
      mouthrinse, toothpaste, slurries with high (HA) or low (LA) air content, or a
      placebo. Vitality of plaque bacteria was investigated before and at 1, 2, 3, 4,
      6, and 8h after application of ASF. ANOVA was applied on a 0.05 significance
      level. RESULTS: Highest reduction of plaque vitality resulted after toothpaste
      application, followed by mouthrinse, LA, and HA slurry. No changes occurred in
      the placebo group. Compared to baseline and placebo, statistically significant
      changes were detected up to 4h in all ASF groups. Toothpaste exerted
      antibacterial efficacy up to 8h. Vitality reduction was higher in the LA group
      than in the HA group. CONCLUSIONS: The concentration of ASF in formulations
      influences the time course of the antibacterial effect. Contact of ASF
      formulations with air might reduce their efficacy.

PMID- 18720054
TI  - Age-specific associations between dental fear and dental condition among adults
      in Finland.
AB  - OBJECTIVE: Our objective was to study whether dental condition, measured by
      numbers of sound, decayed, missing, and restored teeth, was associated with
      dental fear, and whether age, dental attendance, and/or gender modified this
      association. MATERIAL AND METHODS: The sample (n=8,028) comprised Finnish adults
      aged 30 years and older and the study included people (n=6,335) who participated
      in a home interview and a clinical dental examination. Dental fear was measured
      by the question: "How afraid are you of visiting a dentist?" Multiple logistic
      regression analysis was used to determine the association between dental fear and
      dental condition variables, i.e. numbers of decayed, missing, sound, and restored
      teeth considering the effects of age, attendance, and gender. RESULTS: With the
      exception of number of restored teeth, all dental condition variables were
      associated with dental fear. The association between dental fear and number of
      decayed teeth was positive and was independent of age, gender, and attendance.
      Age modified the association between dental fear and number of missing and sound
      teeth. Among the oldest age group, the numbers of missing and sound teeth were
      positively associated with dental fear while being negatively associated among
      the youngest age group. CONCLUSIONS: People with high dental fear have poorer
      dental condition than those with lower fear. Neither gender nor dental attendance
      affects the association between dental fear and dental condition. The
      associations between dental fear and numbers of missing and sound teeth vary
      according to year of birth.

PMID- 18720055
TI  - DICOM Metadata repository for technical information in digital medical images.
AB  - The diagnostic medical image contains, apart from the pixel data, a detailed
      description of how the image was produced. The information reveals details on
      image geometry, radiation data as well as more complex quality index in a varying
      degree, mostly dependent on the age of the equipment. There is no simple way to
      retrieve, process and display this data in a general image workstation. MATERIAL
      AND METHODS: Since November 2004 a DICOM metadata repository has been used to
      record image header parameters. The automated data extraction, storage and
      display are based on simple standard programming and have performed without
      malfunction since the start, today containing metadata from 18 million images.
      RESULTS: The data in the metadata repository has been used in dose optimization
      for a Computed Radiography image plate system, analyzing the exposure index and
      making use of the possibilities to organize the data in examinations, projections
      as well as examination rooms. Analysis of exposure index in the context of these
      parameters shows promising qualities as it makes detection of dosimetric problems
      as well as follow-up of dose adjustments simpler. Current work is aimed at
      creating a vendor independent platform and to further develop methods to support
      dose optimization for flat panel direct digital detectors and computed tomography
      (CT) systems. The possibilities to detect equipment malfunction will be further
      investigated.

PMID- 18720056
TI  - DMLC motion tracking of moving targets for intensity modulated arc therapy
      treatment: a feasibility study.
AB  - PURPOSE: Intensity modulated arc therapy offers great advantages with the
      capability of delivering a fast and highly conformal treatment. However, moving
      targets represent a major challenge. By monitoring a moving target it is possible
      to make the beam follow the motion, shaped by a Dynamic MLC (DMLC). The aim of
      this work was to evaluate the dose delivered to moving targets using the RapidArc
      (Varian Medical Systems, Inc.) technology with and without a DMLC tracking
      algorithm. MATERIAL AND METHODS: A Varian Clinac iX was equipped with a
      preclinical RapidArc and a 3D DMLC tracking application. A motion platform was
      placed on the couch, with the detectors on top: a PTW seven29 and a Scandidos
      Delta4. One lung plan and one prostate plan were delivered. Motion was monitored
      using a Real-time Position Management (RPM) system. Reference measurements were
      performed for both plans with both detectors at state (0) "static, no tracking".
      Comparing measurements were made at state (1) "motion, no tracking" and state (2)
      "motion, tracking". RESULTS: Gamma analysis showed a significant improvement from
      measurements of state (1) to measurements of state (2) compared to the state (0)
      measurements: Lung plan; from 87 to 97% pass. Prostate plan; from 81 to 88% pass.
      Sub-beam information gave a much reduced pattern of periodically spatial
      deviating dose points for state (2) than for state (1). Iso-dose curve
      comparisons showed a slightly better agreement between state (0) and state (2)
      than between state (0) and state (1). CONCLUSIONS: DMLC tracking together with
      RapidArc make a feasible combination and is capable of improving the dose
      distribution delivered to a moving target. It seems to be of importance to
      minimize noise influencing the tracking, to gain the full benefit from the
      application.

PMID- 18720058
TI  - Imaging analysis in cases with inflammation-induced sensorineural hearing loss.
AB  - CONCLUSION: 3D-FLAIR imaging is sensitive to inflammatory inner ear disturbances
      and may be a useful method in investigating the severity of inner ear disturbance
      in cases of inflammation-induced SNHL. OBJECTIVE: To evaluate the usefulness of
      the three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic
      resonance imaging (MRI) sequence in investigating different etiology of inner ear
      disturbances in cases with inflammation-induced acute sensorineural hearing loss
      (SNHL). PATIENTS AND METHODS: Five cases with inflammation-induced acute SNHL by
      different conditions are included in this study: acute meningitis, acute otitis
      media, and Wegener granulomatosis. Imaging analysis was performed using a three
      dimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance
      imaging (MRI) sequence, and correlation between clinical symptoms and FLAIR
      abnormalities was evaluated. RESULTS: In the affected ears in all cases, 3D-FLAIR
      revealed high pre-contrast signal and increased signal in the cochlea after the
      administration of gadolinium. Enhancement was still observed in the inner ear
      after several months with continuing nystagmus in those cases induced by
      meningitis and severe otitis media. In a case with Wegener granulomatosis,
      increased signal in the post-contrast images was stronger on the side of the
      cochlea with the worse hearing level.

PMID- 18720057
TI  - Identifying stable reference genes for evaluation of antioxidative enzyme gene
      expression in auditory cortex and cochlea of young and old Fischer 344 rats.
AB  - CONCLUSION: This study suggests that the validation of reference genes is
      important for the accurate evaluation of differential gene expression in age
      related hearing loss (AHL). OBJECTIVES: To identify the most stable reference
      gene in the auditory cortex and cochlea of young and old rats. Materials and
      methods. mRNA levels of some common reference genes such as beta-actin,
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ubiquitin C, hypoxanthine
      phosphoribosyl-transferase and eukaryotic translation elongation factor (EF) were
      quantified in the auditory cortex and cochlea of young and old rats by
      quantitative RT-PCR, and then their stability was evaluated using GeNorm and
      Normfinder software. RESULTS: There were some variations in the expression of
      reference genes found in the auditory cortex and cochlea of rats, wherein EF and
      GAPDH were identified as the most stable reference genes in auditory cortex and
      cochlea, respectively. mRNA levels of Cu/Zn-superoxide dismutase (SOD), Mn-SOD,
      catalase and glutathione peroxidase in the auditory cortex and cochlea do not
      vary significantly in young and old rats, when they are normalized with EF or
      GAPDH, the valid reference genes, respectively. However, Cu/Zn-SOD and catalase
      levels differ significantly in the auditory cortex when they are normalized with
      beta-actin, an invalid reference gene, resulting in the misinterpretation of the
      target gene expression levels.

PMID- 18720059
TI  - Up-regulation of neutrophil gelatinase-associated lipocalin in cholesteatoma.
AB  - CONCLUSION: Neutrophil gelatinase-associated lipocalin (NGAL) and Ki-67
      expression were up-regulated in cholesteatoma and the expression pattern of NGAL
      in the epithelial layer was inversely related to the expression of Ki-67.
      Therefore, NGAL may be related to dysregulated differentiation in the
      keratinocytes during the development of a cholesteatoma. OBJECTIVES: We
      investigated the differential expression and localization of NGAL in middle ear
      cholesteatoma and compared the results to normal external auditory canal (EAC)
      skin. We also compared the expression and localization of NGAL with the
      expression and localization of Ki-67 in middle ear cholesteatoma. SUBJECTS AND
      METHODS: Tissue samples from middle ear cholesteatomas and normal EAC skin were
      obtained from 20 patients undergoing middle ear surgery. NGAL mRNA expression was
      determined by the reverse transcriptase-polymerase chain reaction (RT-PCR). The
      expression of NGAL protein was analyzed by Western blot. NGAL and Ki-67 were
      localized by immunohistochemical staining. RESULTS: A significantly greater
      expression of the NGAL mRNA was observed in cholesteatoma epithelium than in
      normal EAC skin (p < 0.05). NGAL was detected in the granular layer of
      cholesteatoma. However, NGAL was scarcely expressed in normal EAC skin. Ki-67 was
      detected predominantly in the basal and parabasal layers of cholesteatoma
      epithelium.

PMID- 18720060
TI  - Epstein-Barr virus infection and plasma transforming growth factor-beta1 levels
      in head and neck cancers.
AB  - CONCLUSIONS: In addition to the correlation of transforming growth factor (TGF)
      beta1 levels to the radiation toxicity, both Epstein-Barr virus (EBV) infection
      and postoperative status play roles in the change in plasma TGF-beta1 levels in
      patients with head and neck cancers. OBJECTIVES: To assess the parameters
      involved in the change in plasma TGF-beta1 level during concurrent
      chemoradiotherapy (CCRT). PATIENTS AND METHODS: Blood samples (n=307) before,
      during, and after treatment were obtained from 39 patients with head and neck
      cancers treated with definitive or adjuvant CCRT. In situ hybridization (ISH) was
      used to identify EBV-encoded RNA (EBER) in tissues from the primary tumor or
      metastatic lymph nodes. Plasma TGF-beta1 level, white blood cell (WBC), and
      platelet count were assayed immediately before the first fraction of radiotherapy
      (RT), once a week during RT, and at the end of the RT course. The grades of
      mucositis and dermatitis were recorded weekly during CCRT. RESULTS: Pretreatment
      TGF-beta1 level and radiation toxicity were found to be significantly correlated
      with the increase of the plasma TGF-beta1 level during CCRT (p<0.05), but
      correlation of platelet count was only found in patients whose tumors were EBV
      positive (p=0.0042), and WBC count in those treated with postoperative adjuvant
      CCRT (p=0.004).

PMID- 18720061
TI  - The large Chinese family with Y-linked hearing loss revisited: clinical
      investigation.
AB  - CONCLUSION: The DFNY1 phenotypes shared many characteristics with some autosomal
      dominant hearing loss, in the aspects of age of onset, severity and audiometric
      configuration. However, the typical, outstanding feature of this trait was its
      remarkable pattern of inheritance. Similar traits, if ever encountered, can be
      most easily identified by discerning this exceptional and rare pattern of
      inheritance. OBJECTIVES: To analyze the audiological features in Chinese Y-linked
      non-syndromic hearing impairment, the extended DFNY1 family. SUBJECTS AND
      METHODS: A nine-generation Chinese family (DFNY1) was ascertained and expanded
      from the year of 2000 to 2006. The audiometric evaluations included pure-tone
      audiometry, tympanometry, and auditory brainstem responses. Some subjects
      received computerized tomography scan of the temporal bone. RESULTS: 52 out of
      276 members in this family received clinical examinations. 24 live subjects had
      hearing impairment consisting of 23 patrilineal males and one female. In the
      affected lineage, 92% patrilineal males were well characterized as having hearing
      loss and 2 children remained to be diagnosed. Based on the audiological
      examinations on the male members, the degree of hearing loss was from mild (3
      patients), moderate (7 patients) to severe (11 patients). The audiometry
      displayed 48% subjects with sloping in high frequencies, 38% flat in all
      frequencies, and the rest (14%) the U-shape. The age of onset ranged from 5-27
      years with the average of 11.5 years.

PMID- 18720062
TI  - Alcohol affects otolith-induced ocular counterrolling: dosage effects.
AB  - CONCLUSION: Otolith function is significantly affected by alcohol ingestion and
      the higher the dosage, the greater the effect. OBJECTIVE: To determine how the
      effect of a 5 oz (150 ml) dose of alcohol differs from an earlier study examining
      the effect of 3 oz (90 ml) on ocular counterrolling (OCR). SUBJECTS AND METHODS:
      Twenty subjects underwent OCR testing before and after drinking 5 oz of 80 proof
      vodka. RESULTS: Blood alcohol levels (BAL) of the subjects ranged from 0.09 to
      0.18%. Three measures of OCR were considered. Amplitude was significantly reduced
      post-alcohol; disconjugacy was significantly increased post-alcohol; smoothness
      was not significantly different pre- and post-alcohol. In contrast, the lower 3
      oz study produced BAL of 0.04-0.09% and resulted in significantly reduced OCR
      amplitude, no significant change in disconjugacy, but a significant improvement
      in smoothness. The increase in BAL produced further impairment of amplitude and
      conjugacy but eliminated the benefit of smoothness.

PMID- 18720063
TI  - Infrared video patch-clamp technique for spiral ganglion neurons in rat cochlear
      slices.
AB  - CONCLUSION: Cochlear slice and infrared video patch-clamp techniques can be used
      in real-time observation. They provide a good method and platform for further
      study of the electrophysiological properties and auditory transduction mechanism
      of spiral ganglion neuron (SGN). OBJECTIVE: To establish the isolated rat
      cochlear slice technique combined with the infrared video patch-clamp technique
      to explore the electrophysiological properties of the SGN. MATERIALS AND METHODS:
      SD rats were divided into three groups according to postnatal days (0-2 days, 3-6
      days and 7-14 days). After quickly making SD rat cochlear slices, the
      electrophysiological properties of the SGN were observed using the infrared
      differential interference contrast technique and patch-clamp recording, and the
      factors that affect the cochlear slice quality and patch-clamp recording were
      analysed. RESULTS: The successful slice rate was highest in 3-6-day-old SD rats
      and two to four slices could be prepared using each cochlea. It is crucial to
      maintain the connection of partial skull with the cochlea and the volute
      integrity when producing slices. The position of the cochlear axis and blade, and
      the slice preparation time were also important factors affecting slice quality
      and cell activity. SGN cells in good condition could easily be found using the
      infrared video patch-clamp technique to help the assessment of the seal test
      process. SGN resting membrane potential of whole-cell recording was -45.6+/-5.3
      mV (n=52) and the currents of Na+ and K+ could be recorded.

PMID- 18720064
TI  - Retinoic acid applied after noise exposure can recover the noise-induced hearing
      loss in mice.
AB  - CONCLUSION: The early post-exposure treatment with All-trans retinoic acid (ATRA)
      can reduce hair cell loss and hearing deterioration in mice in which permanent
      threshold shift has been induced. OBJECTIVE: One of the mechanism by which
      intense noise induces apoptosis of cochlea hair cells is the C-Jun NH(2)-terminal
      kinase (JNK) pathway. ATRA is a potent inhibitor of activator protein 1, a
      transcription factor of the JNK pathway. In this study we evaluated that the
      effect of post-exposure treatment of ATRA on noise-induced hearing loss and aimed
      to determine a time window for effective post-exposure treatment of ATRA.
      METHODS: All mice were exposed to white noise for 3 h per day for three
      consecutive days and induced permanent threshold shift. The treatment groups fed
      with ATRA from 1 h, one day, two days, and three days after noise exposure for
      five days were compared with mice fed with same dosage of sesame oil. We measured
      the threshold shifts of hearing and survival rates of hair cells on the
      cytocochleogram. RESULTS: Mice fed with ATRA beginning within two days after
      noise had less threshold shifts and more hair cell survivals than mice fed with
      sesame oil.

PMID- 18720065
TI  - The limits of stability in patients with Meniere's disease.
AB  - OBJECTIVE: To determine the ability of patients with unilateral Meniere's disease
      (MD) to reach the corresponding limits of stability and to define the existence
      of directional constraints. PATIENTS: 112 patients with unilateral MD and 30
      normal age-matched subjects with no history of equilibrium problems. METHODS: A
      computerized dynamic posturography system was used to test the ability of
      subjects to displace their centre of pressure (COP) to the corresponding limits
      of stability. The eight targets used were separated by 45 degrees to form a
      circle around the subject who had to displace their COP to the target. Reaction
      time, velocity, accuracy and an overall evaluation of the intended movement
      towards and away from the target were analysed. Other characteristics of the
      patients were also assessed. RESULTS: A small but significant correlation was
      found between auditory and vestibular deficit and the different variables studied
      in the limits of stability test. Three factors were derived from variables
      obtained with short displacements, and the results are significantly different
      between patients and controls and are correlated with the period since the last
      vertigo spell, the level of disability, hearing loss and vestibular deficit.
      CONCLUSIONS: Dynamic balance is moderately impaired in patients with Meniere's
      disease.

PMID- 18720066
TI  - Three-dimensional images of the reuniting duct using cone beam CT.
AB  - CONCLUSION: There is a bony groove under the course of the reuniting duct of the
      inner ear. Cone beam CT could show three-dimensional (3D) reconstruction images
      of this groove in a cadaver and living human subjects. OBJECTIVE: To obtain
      simple and universal images of the reuniting duct in humans for clinical use.
      MATERIALS AND METHODS: We investigated the reuniting duct macroscopically by
      observing the temporal bone in cadavers and living human subjects using cone beam
      CT. 3D reconstruction images of the duct were analyzed by the rendering software
      IVIEW. RESULTS: The reuniting duct showed a bony groove between the saccule and
      cecum of the hook portion of the cochlea that could be three-dimensionally
      visualized by cone beam CT. A bony groove image in a living human subject could
      also be visualized by cone beam CT.

PMID- 18720067
TI  - A randomized prospective study comparing medical and medical-surgical treatment
      of nasal polyposis by CT.
AB  - CONCLUSIONS: CT of the sinuses showed long-lasting improvement in the total and
      CT scores of the osteomeatal complex (OMC) after combined surgical and
      corticosteroid treatment as compared with medical treatment alone. However, the
      correlations between the improved CT scores and the patients' symptoms, olfactory
      thresholds or polyp scores were generally not significant. OBJECTIVE: To evaluate
      CT scans as a method for comparing the effect of medical treatment versus
      combined surgical and medical treatment of nasal polyposis. PATIENTS AND METHODS:
      Thirty-two patients with nasal polyposis were randomized to unilateral endoscopic
      sinus surgery after pretreatment with oral prednisolone for 10 days and nasal
      budesonide bilaterally for 1 month. Postoperatively, they were given nasal
      steroids (budesonide) bilaterally for 1 year. They were assessed with nasal
      endoscopy, symptom scores, and olfactory thresholds and followed for 12 months.
      CT of the sinuses was performed before and 1 year after operation. The CT scans
      were evaluated using the Lund staging system. RESULTS: From before surgery to 1
      year after surgery, we found a significant improvement on the operated side in
      the CT total scores, and scores of the OMC and the maxillary sinus, but no
      significant differences on the unoperated side. Significant correlations were
      also noted between the differences in olfactory thresholds between the operated
      and unoperated sides.

PMID- 18720068
TI  - Tracheal resection with end-to-end anastomosis preserving paries membranaceus
      trachea for patients with papillary thyroid carcinoma.
AB  - CONCLUSION: Sleeve resection of the trachea while preserving the paries
      membranaceus trachea appears useful for patients in whom papillary thyroid
      carcinoma has invaded as far as the tracheal mucosa. OBJECTIVES: While tracheal
      sleeve resection with end-to-end anastomosis is advantageous, risks of suture
      failure or other serious complications exist. Since feeding arteries enter the
      trachea from the posterior and lateral walls, we conduct tracheal anastomosis
      preserving the paries membranaceus trachea. PATIENTS AND METHODS: This study
      retrospectively examined therapeutic outcomes and postoperative complications for
      sleeve resection followed by end-to-end anastomosis in 12 patients between 1994
      and 2005. RESULTS: Tracheal suture failure occurred in one patient and sutures
      were redone. One patient developed esophageal fistula, but recovered with
      conservative treatment. One patient required re-intubation. In three patients,
      recurrent laryngeal nerves were paralyzed bilaterally. No patients displayed
      recurrence in the tracheal resection margin or preserved paries membranaceus
      trachea. The 10-year survival rate was 72.9%.

PMID- 18720069
TI  - The costs and quality of operative training for residents in tympanoplasty type
      I.
AB  - CONCLUSION: A teaching hospital would incur more operation room costs on training
      surgical residents. OBJECTIVE: To evaluate the increased operation time and the
      increased operation room costs of operations performed by surgical residents. As
      a model we used a very common surgical otology procedure -- tympanoplasty type I.
      SUBJECTS AND METHODS: From January 1, 2004 to December 31, 2004, we included in
      this study 100 patients who received tympanoplasty type I in Taipei Veterans
      General Hospital. Fifty-six procedures were performed by a single board-certified
      surgeon and 44 procedures were performed by residents. We analyzed the operation
      time and surgical outcomes in these two groups of patients. The operation room
      cost per minute was obtained by dividing the total operation room expenses by
      total operation time in the year 2004. RESULTS: The average operation time of
      residents was 116.47 min, which was significantly longer (p<0.0001) than that of
      the board-certified surgeon (average 81.07 min). It cost USD $40.36 more for each
      operation performed by residents in terms of operation room costs. The surgical
      success rate of residents was 81.82%, which was significantly lower (p=0.016)
      than that of the board-certified surgeon (96.43%).

PMID- 18720070
TI  - How we do it: a combined method of traditional curette and power-assisted
      endoscopic adenoidectomy.
AB  - CONCLUSION: After conventional curette adenoidectomy, a significant mass of
      residual adenoid tissue is observed in about 50% of the cases. The combined
      approach of conventional curette and endoscopic adenoidectomy with microdebrider
      assures a complete and accurate removal of the mass. It is an effective and safe
      method without significantly prolonging the operative time. OBJECTIVES: To
      describe the surgical technique of conventional curette adenoidectomy completed
      with the microdebrider under endoscopic vision in case of residual adenoid
      tissue. PATIENTS AND METHODS: This was a retrospective review of 143 consecutive
      patients (age range 2-16 years, mean 6.2) who underwent endoscopic adenoidectomy
      for adenoid hypertrophy at an academic hospital-based institution. A classic
      transoral curette adenoidectomy was performed initially. Then a rigid fibre-optic
      endoscope was used transnasally to assess the completeness of surgery. Residual
      adenoid tissue was removed using a microdebrider under endoscopic vision.
      RESULTS: After conventional curette adenoidectomy 70 children (48.9%) underwent
      residual adenoid tissue transnasal removal. Mean curette adenoidectomy time with
      endoscopic visualization of the nasopharynx was 9.1 min and, in the case of
      completion with the microdebrider, 14.6 min. No significant intraoperative
      bleeding, postoperative haemorrhage or other complications have occurred. After a
      mean follow-up of 24.4 months, no patients have been readmitted for symptoms of
      adenoid regrowth.

PMID- 18720071
TI  - The intravestibular source of the vestibular aqueduct: Its structure and
      pathology in Meniere's disease.
AB  - CONCLUSION: We describe a thin, highly vascular layer of mineralized cartilage,
      which surrounds most of the endolymphatic duct. In the normal ear this may act in
      helping to control the chemical composition of endolymph. In Meniere's disease
      (MD) there is a marked apoptotic change among the mineralized cartilage cells of
      this layer, which seems to be associated also with the deposition of a
      pathological substance in the walls of many blood vessels. This may lead to
      serious chemical change in the nearby endolymph and so provoke the symptoms of
      MD. OBJECTIVES: Endolymphatic hydrops is found in all cases of MD, but is not
      specific for that condition. We sought a cellular change in the vicinity of the
      saccule that might be more specific than the lesion of endolymphatic hydrops and
      thus lead to a more successful management of the disease. MATERIALS AND METHODS:
      We examined stained step sections of 33 autopsy temporal bones from 20 cases of
      MD, particularly in the region of the vestibule, and compared the changes with
      those found in a similar region of 65 temporal bones taken from randomly selected
      cases of non-Meniere conditions. RESULTS: In all temporal bones there was a well
      demarcated region of the posterior vestibule, which formed a skeletal arch around
      the opening of the tunnel of the vestibular aqueduct into which the endolymphatic
      duct entered from the vestibule. This 'vestibular arch' was composed mainly of
      blood vessels and mineralized chondrocytes. The inner skeletal layer surrounding
      the course of most of the endolymphatic duct in the tunnel of the vestibular
      aqueduct was composed of the same tissue and was in fact continuous with the
      vestibular arch. In the non-Meniere temporal bones the mineralized chondrocytes
      were congregated around normal thin-walled blood vessels and small numbers of
      them seemed to be undergoing apoptosis in this vicinity. In all of the MD
      temporal bones, except five in which the vestibular arch was either absent or
      atrophic, we found pronounced changes of apoptosis among the mineralized
      cartilage cells and these were associated with proliferative changes in blood
      vessels in which a bluish-staining translucent deposit, possibly mineralization
      of the vascular wall, was prominent.

PMID- 18720072
TI  - Effects of Piezosurgery on the cochlear outer hair cells.
AB  - CONCLUSIONS: The absence of audiologic side effects highlights the reduced trauma
      of the piezoelectric cut, demonstrates the superiority of the Piezosurgery device
      in terms of safety and protection of anatomical structures and confirms its
      applicability in all the otologic techniques tested. OBJECTIVES: The aim of the
      present study was to estimate the effect of Piezosurgery on the cochlea and in
      particular on the cochlear outer hair cells. PATIENTS AND METHODS: We selected 60
      patients with a history of otologic surgery with Piezosurgery. Before and 6
      months after surgery, all the patients underwent the following instrumental
      examinations: pure-tone audiometry, tympanometry, transient evoked otoacoustic
      emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs) and
      auditory brainstem response (ABR). RESULTS: Piezosurgery showed its safety on the
      inner ear and in particular on the cochlear outer hair cells: for each
      instrumental examination (pure-tone audiometry, tympanometry, TEOAE, DPOAEs and
      ABR), no patients presented postoperative worsening.

PMID- 18720073
TI  - Histomorphologic study of nasal turbinates after surgical treatment: a comparison
      of laser surgery and radiofrequency-induced thermotherapy effects in animals.
AB  - CONCLUSIONS: From the clinical point of view, the healing process following
      radiofrequency-induced thermotherapy (RFITT) is faster and less painful for the
      patient. This corresponds with the histopathological findings, as in a case of
      diode laser treatment, the damage to the tissue was greater, and the regenerative
      and reparative processes were less prominent. OBJECTIVE: Comparison of
      histopathologic changes and the healing process in the turbinate tissue regarding
      the kind of treatment and intensity of energy used for surgery. MATERIALS AND
      METHODS: Pigs were chosen as laboratory animals for this study. The animals were
      divided into two groups. Two different techniques were used: treatment with diode
      laser fiber applied submucosally in contact mode and RFITT. The first tissue
      samples were taken on the third postoperative day; further sampling was done on
      the eight postoperative day. RESULTS: Histological features of the specimens
      taken from turbinates 8 days after the surgery included necrosis and ulceration,
      fibrin deposition in the mucosa, necrotizing sialometaplasia, as well as
      proliferation of the granulation tissue. Generally, the changes found in the
      turbinates treated by diode laser were more severe, with more intensive tissue
      damage and less prominent regenerative and reparative changes.

PMID- 18720074
TI  - Facial nerve stimulation after cochlear implantation according to types of
      Nucleus 24-channel electrode arrays.
AB  - CONCLUSION: In this study, we concluded that electrode design and location did
      not have a high level of influence on the prevalence of facial nerve stimulation
      (FNS) in normal cochleae. OBJECTIVE: To analysis the prevalence of FNS after
      cochlear implantation with Nucleus 24-channel devices according to types of
      electrodes arrays. PATIENTS AND METHODS: We retrospectively analyzed medical and
      mapping records of 394 patients who received cochlear implants (CIs) manufactured
      by Cochlear Corporation from April 1999 to March 2007. RESULTS: In all, 23 of 394
      (5.8%) patients had FNS (CI24M 4 of 39 [10.3%], CI24RCS 9 of 192 [4.7%], CI24RST
      9 of 21 [42.9%], and CI24RECA 1 of 87 [1.1%]). In addition, 4 of 324 (1.2%)
      patients with normal cochleae complained of FNS (CI24M 1 of 33 [3.0%], CI24RCS 2
      of 173 [1.2%], and CI24RECA 1 of 71 [1.4%]). There was no difference between
      straight and perimodiolar electrode arrays in patients with normal cochleae. In
      addition, when comparing two types of Contour electrodes, Contour Advance (soft
      tip) electrodes offered significantly lower incidence of FNS than Contour
      electrode arrays. We could manage these patients with methods such as decrease of
      C-level, selective channel turning off, and changes of mapping strategies.

PMID- 18720075
TI  - Overexpression of thymic stromal lymphopoietin in allergic rhinitis.
AB  - CONCLUSION: Thymic stromal lymphopoietin (TSLP) played an important role in the
      pathogenesis of allergic rhinitis (AR) and can be regarded a potential
      therapeutic target for the management of AR. OBJECTIVE: To evaluate the possible
      role of TSLP in the pathogenesis of AR. PATIENTS AND METHODS: We enrolled 16
      patients of AR to investigate the expression of TSLP in nasal mucosa and evaluate
      the link of TSLP and interleukin-4 (IL-4). Expression of TSLP was detected by
      immunohistochemical analysis and quantitative reverse transcriptase-polymerase
      chain reaction (RT-PCR), and concentrations of TSLP and IL-4 were measured by
      enzyme-linked immunosorbent assay (ELISA). RESULTS: TSLP was detected in all
      samples and the mRNA and protein expression of TSLP is increased significantly in
      AR nasal mucosa compared with normal control (P<0.05). TSLP production is tightly
      correlated with IL-4 and severity of AR (P<0.05).

PMID- 18720076
TI  - Malformation of the external ear and facial paralysis caused by megatemperature
      hydro-aluminum.
AB  - We present a case of right lateral auricle contracture malformation, auricular
      canal atresia, and complete facial paralysis (House-Brackmann grade VI) caused by
      a megatemperature hydro-aluminum injury at work. The diastrophic auricle and
      auricular canal atresia were reshaped. The complete facial paralysis was
      reanimated to House-Brackmann grade III after surgical hypoglossal-facial end-to
      end anastomosis. These outcomes indicate that hypoglossal-facial end-to-end
      anastomosis is an effective surgical option for successful reanimation of
      complete facial paralysis.

PMID- 18720077
TI  - Neuroprotective effects of vitamin E on adult rat motor neurones following facial
      nerve avulsion.
AB  - CONCLUSION: The present study demonstrates the neuroprotective effect of vitamin
      E after peripheral facial nerve injury. Antioxidants may have therapeutic
      potential in traumatic facial nerve dysfunction resulting from traumatic temporal
      bone injury and ear surgery. OBJECTIVE: We investigated the possible
      neuroprotective effect of vitamin E on the facial motor nucleus (FMN) motor
      neurones after peripheral nerve avulsion. METHODS: In 36 adult rats, the right
      facial nerve was avulsed from the stylomastoid foramen. Following nerve avulsion,
      immunohistochemistry was used to investigate the effects of vitamin E on 4
      hydroxynonenal (HNE) activity. FMN motor neurones and glial cells were counted
      bilaterally in sections stained with cresyl violet. RESULTS: Rats administered
      vitamin E exhibited clear suppression of injury-induced neuronal HNE expression
      in the ipsilateral FMN as compared to non-treated controls. Following nerve
      avulsion, the number of surviving motor neurones in the ipsilateral FMN was
      significantly greater among vitamin E-treated rats than non-treated controls.

PMID- 18720078
TI  - Radical ablative surgery and radial forearm free flap (RFFF) reconstruction for
      patients with oral or oropharyngeal cancer: postoperative outcomes and oncologic
      and functional results.
AB  - CONCLUSIONS: Radical ablative surgery and radial forearm free flap (RFFF)
      reconstruction provide promising oncologic and functional results in patients
      with oral or oropharyngeal cancer. OBJECTIVES: To assess the postoperative
      outcomes and the oncologic and functional results, with their main predictive
      factors, after radical ablative surgery and RFFF reconstruction for patients with
      oral or oropharyngeal cancer. PATIENTS AND METHODS: Between 2000 and 2006, we
      prospectively analyzed the postoperative, oncologic and functional outcomes of
      all previously untreated patients who underwent this type of surgery. RESULTS: A
      total of 132 patients were enrolled in this study. There were three RFFF
      failures. The rate of surgical complications was 20%. The 5-year locoregional
      control and overall survival rates were 68% and 52%, respectively. Advanced age,
      high comorbidity index, elevated overall stage and tumoral involvement of the
      inner part of the cheek were correlated with a lower overall survival rate. A
      good functional result was obtained for oral diet, speech, mouth opening and
      aesthetic outcome in 87%, 80%, 86% and 88% of the patients, respectively. High
      comorbidity index, large flap surface, radiotherapy and tumoral involvement of
      the mobile tongue were significant predictors of poorer functional or aesthetic
      outcomes.

PMID- 18720079
TI  - Expression profiling of supraglottic carcinoma: PTEN and thrombospondin 2 are
      associated with inhibition of lymphatic metastasis.
AB  - CONCLUSION: Down-regulation of metastasis inhibitor genes PTEN and thrombospondin
      2 may play a role in the lymphatic metastasis of supraglottic carcinoma.
      OBJECTIVES: To investigate differentially expressed genes in supraglottic
      squamous cell carcinoma with and without lymphatic metastasis using cDNA
      microarray. MATERIALS AND METHODS: cDNA microarray was used to detect the
      expression profiles of supraglottic carcinoma and the results were validated with
      real-time PCR. RESULTS: Compared with normal laryngeal tissues, the expression of
      15.6% (15/96) genes including cathepsin B, cathepsin D, cathepsin L, Ets1, c
      Ets2, and PEA3 were up-regulated in both cases of supraglottic carcinoma.
      Compared with the supraglottic carcinoma with no lymph node metastasis, the
      expression of metastasis inhibitor genes PTEN and thrombospondin 2 was down
      regulated in the supraglottic carcinoma tissue with lymph node metastasis.

PMID- 18720080
TI  - Enhanced FDG uptake in brown tumors mimics multiple skeletal metastases in a
      patient with primary hyperparathyroidism.

PMID- 18720081
TI  - A piglet model for detection of hypoxic-ischemic brain injury with magnetic
      resonance imaging.
AB  - BACKGROUND: Early detection of hypoxic-ischemic (HI) injury in the asphyxic
      newborn is important because present prognostic factors are inadequate.
      Furthermore, therapeutic interventions may have additional benefit if initiated
      in time. PURPOSE: To assess whether the use of a combined protocol including
      conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI),
      diffusion tensor imaging (DTI), and proton MR spectroscopy (MRS) could detect
      pathological findings in a piglet model 7 hours after HI. MATERIAL AND METHODS:
      Ten piglets were submitted to HI for 30 min followed by reoxygenation with 21% O2
      for 7 hours. MRI at 1.5T was done prior to and 7 hours after the HI. Single-voxel
      proton MRS was performed, and apparent diffusion coefficient (ADC) and fractional
      anisotropy (FA) were measured in the basal ganglia. MRS identified N
      acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac). Histology
      and microtubule-associated protein 2 (MAP-2) staining was performed in the basal
      ganglia at the end of the experiment. RESULTS: Compared to baseline, ADC,
      NAA/Cho, and NAA/Cr were significantly reduced after 7 hours (P<0.001, P=0.01,
      and P=0.05, respectively) and FA values were increased (P<0.025). The ratios of
      Lac/Cho and Lac/NAA were significantly higher after 7 hours compared to baseline
      (P<0.001). Presence of necrosis correlated well with reduced ADC (R(S)=0.91) and
      presence of Lac (R(S)=0.80). Histology and MAP-2 staining showed more than 90%
      necrosis in eight piglets, 60% in one piglet, and no necrosis in one piglet.
      CONCLUSION: Diffusion MRI and proton MRS can detect HI injury in the piglet brain
      7 hours after hypoxia. DWI and MRS can be used to give useful prognostic
      information. This piglet model may potentially be used to mimic clinical
      situations and is suitable for further research investigating HI injury.

PMID- 18720082
TI  - Recurrence after percutaneous ethanol ablation of simple hepatic, renal, and
      splenic cysts: is it true recurrence requiring an additional treatment?
AB  - BACKGROUND: Recurrence after percutaneous ethanol ablation (PEA) of benign
      hepatic and renal cysts has been common, resulting in re-treatment or additional
      surgery. However, in recent years, a few cases of spontaneous regression of
      recurrent cysts following PEA have been experienced, which led to the design of
      this study to evaluate cyst recurrence after PEA and the necessity of additional
      treatment. PURPOSE: To evaluate whether the initial recurrence after PEA of
      benign hepatic, renal, and splenic cysts is true recurrence, and to decide
      whether additional treatment is needed. MATERIAL AND METHODS: Thirty-nine benign
      cysts (21 hepatic, 17 renal, and one splenic) were treated with PEA. PEA was
      performed with injection of 13-900 ml (40-50% of the volume of aspirated fluid)
      of absolute ethanol into the cysts. For cysts larger than 100 ml, two or more
      PEAs were given in one session. Ultrasonography was then performed during a
      period of 12 months with 1-2-month intervals. RESULTS: Two months after PEA,
      eight cysts (20.5%) regressed completely; another 31 cysts recurred with
      decreased size. After 6 months, 10 of the recurrent cysts had regressed
      spontaneously. Another four recurrent cysts regressed after 8 months, and three
      regressed after 12 months. Hence, 25 out of 39 (64.1%) cysts regressed within 12
      months after PEA. The mean regression time of the 25 recurrent cysts was 6.3
      months. All recurrent cysts, including the 14 that were lost to complete follow
      up, showed gradual decrease overtime. There were no major complications
      associated with PEA. CONCLUSION: Initial relapse of a cyst following PEA does not
      signify true recurrence, but transient, reactive, or inflammatory fluid
      collections which eventually disappear within several months, and thus does not
      necessitate additional treatment.

PMID- 18720083
TI  - Phantom-calibrated versus automatic coronary artery mass quantification with
      multidetector-row computed tomography: in vitro and in vivo study.
AB  - BACKGROUND: Coronary artery calcium scoring is used as a method for
      cardiovascular risk stratification and monitoring of coronary heart disease.
      Automatic software-based calcium mass calculation has been proposed to improve
      the performance of the procedure. PURPOSE: To compare two algorithms of calcium
      mass measurement, automatic and phantom calibrated, with respect to correlation,
      measurement error, and accuracy in vitro and in vivo. MATERIAL AND METHODS: A
      cardiac phantom with calcium cylinder inserts was scanned with sequential non
      overlapping collimation 4 x 2.5 mm, at 120 kV and 165 mAs. Fifty adults (37 men;
      mean age 46.2 years) were examined with the same settings using prospective
      electrocardiographic triggering to detect and quantify coronary artery
      calcifications. Calculations were performed with two methods: software-based
      automatic calcium mass measurement (ACM) and phantom-calibrated calcium mass
      measurement (CCM). RESULTS: The total phantom calcium masses measured with ACM
      and CCM were 175.0+/-13.8 mg and 163.0+/-4.4 mg, respectively (P<0.0001), and ACM
      produced a higher mean error (4.5 vs. 3.2; P<0.05). Results of ACM and CCM were
      strongly correlated to each other (R=0.73-0.96; P<0.0001). Mean image noise in
      the patient study was 8.72+/-1.68 HU. Results of patient calcium scoring with ACM
      and CCM were significantly different (median 70.3 mg and 59.7 mg, respectively;
      P<0.0001), with a mean systematic error of 17.5% (limit of agreement between
      14.6% and 20.4%). The use of ACM resulted in an altered quartile classification
      for 14% of patients, as compared to CCM; all of these patients were classified
      into a higher category. CONCLUSION: Our data indicate that multidetector-row
      computed tomography coronary calcium mass determination based on dedicated
      phantom calibration shows lower measurement error than an automatic software
      based calculation method. The tested automatic software does not yet seem to be a
      reliable option for calcium mass measurement.

PMID- 18720084
TI  - Longitudinal evaluation of the occurrence of MRI-detectable bone marrow edema in
      osteoarthritis of the knee.
AB  - BACKGROUND: Bone marrow edema (BME) is a condition detectable with magnetic
      resonance imaging (MRI) and is present in different stages of osteoarthritis
      (OA). Its pathogenesis is still not completely known. PURPOSE: To evaluate the
      longitudinal occurrence and persistence of BME in early OA of the knee. MATERIAL
      AND METHODS: Twenty-three patients (eight females, 15 males; mean age 55.5+/-10.3
      years) were scanned with a 1.5T MR imaging unit (sagittal fat-suppressed
      intermediate-weighted fast spin echo; 4-mm section thickness, 1-mm intersection
      gap, 256 x 192 matrix, 120-mm field of view). Images were obtained in all 23
      patients at two time points (TPs) and in 12 patients at three TPs. Images were
      evaluated by two readers independently; discrepancies in image grading were
      reviewed and evaluated in consensus. A four-point image-grading scale was used
      (absence of BME to severe BME). Four main anatomical regions were evaluated
      (medial femur, lateral femur, medial tibia, lateral tibia), which were
      subcategorized into anterior, central, and posterior regions. RESULTS: One
      hundred five areas of BME in the 23 patients were found at all three TPs. In 16
      areas, the BME was consistent at the same location over time, in seven locations
      the BME became larger, in six areas the BME became smaller, and in 16 locations
      it could not be detected in follow-up MRIs. In one case, the BME was smaller at
      TP2 but increased at TP3. In eight cases, only at the last time point could a BME
      be detected. CONCLUSION: BME is not a static phenomenon but changes over time.
      Correlation to physical activity and local inflammatory reaction should be
      evaluated.

PMID- 18720085
TI  - Emergent treatment of variceal bleeding in two infants.
AB  - Two infants with portal hypertension were treated on an emergency basis for life
      threatening uncontrollable variceal bleeding. One 9-month-old girl had portal
      vein thrombosis, and the other 28-months-old girl had liver cirrhosis secondary
      to biliary atresia. Following percutaneous transhepatic embolization of the
      varices, successful bleeding control was achieved in both patients.

PMID- 18720086
TI  - Treatment of intracardiac thrombi with argatroban.
AB  - Intracardiac thrombi are well known complications associated with diverse cardiac
      diseases and venous thromboembolism. Therapeutic recommendations like
      thrombolysis, surgical thrombectomy, or treatment with low molecular heparin and
      intravenous unfractionated heparin based on small numbers of patients or
      retrospective case series have failed to reach a consensus. We report on the use
      of argatroban, a new direct thrombin inhibitor in 4 patients with intracardiac
      thrombi. Therapy was effective in all patients with complete resolution of
      thrombi. Treatment was complicated by recurrent strokes with complete
      neurological recovery in one patient. Therapy of intracardiac thrombi by
      argatroban is safe and effective. The drug requires no dosage adjustments for
      age, sex, or renal impairment, including in dialysis-dependent patients.
      Argatroban has been found to increase predictably activated partial
      thromboplastin time (aPTT) and activated clotting time (ACT) in a dose-dependent
      manner.

PMID- 18720087
TI  - The use of more than one inotrope in acute heart failure is associated with
      increased mortality: a multi-centre observational study.
AB  - BACKGROUND: Although weakly supported by scientific evidence, according to
      guidelines the use of inotropes in acute heart failure is indicated in the
      presence of hypoperfusion refractory to fluid resuscitation. AIMS: We examined
      the characteristics of the inotrope-treated patients, as well as, their in
      hospital mortality. The frequency and dosing of inotropic infusions in patients
      admitted with acute heart failure was assessed in detail. METHODS: We included
      620 consecutive patients with acute heart failure who were admitted to hospital
      during three months during spring 2004 in an observational multi-centre study.
      RESULTS: Of the patients 84 (14%) were treated with inotropes. Dopamine was used
      in 46 (7%), dobutamine 22 (4%), epinephrine 5 (1%), norepinephrine in 33 (5%),
      and levosimendan in 44 (7%) cases. The in-hospital mortality was 21% in the
      inotrope-treated group, and 5% in the control group. The mortality was 7% if only
      one inotrope was used. The mortality increased in proportion to the number of
      inotropes used. Lower blood pressure at admission, low ejection fraction,
      elevated C-reactive protein and cardiac markers correlated with the inotrope
      administration. CONCLUSION: Inotrope administration is a marker of increased
      mortality in patients with acute heart failure. Still, the use of a single
      inotrope during hospital stay seems rather safe.

PMID- 18720088
TI  - Screening for depressive symptoms in an online sample of men who have sex with
      men.
AB  - Depression is a debilitating disorder and relatively high rates have been
      reported in studies of men who have sex with men (MSM). This study was undertaken
      to assess the utility of screening for, and characteristics associated with,
      depressive symptoms in an online survey of MSM. In 2003-2004, an online cross
      sectional study was conducted among 2,964 MSM from the US and Canada. Using the
      two-item Patient Health Questionnaire (PHQ-2), 18% of the study participants
      screened positive for depressive symptoms within the past three months.
      Characteristics associated with a positive PHQ-2 screen for depressive symptoms
      in multivariate analysis included: having less than a high school or college
      degree; being single (not having a primary male partner) or being married to a
      woman; being HIV-positive; and not having recent sex. Additionally, among men who
      screened positive on the PHQ-2, predictors of not having treatment from a mental
      health provider in the past year were: low education; being black/African
      American/Canadian or Hispanic; and having no primary care provider. The Internet
      is a viable medium to reach and screen men at-risk for depression. Future work is
      needed for online outreach and connection to offline assessment as well as
      intervention.

PMID- 18720089
TI  - Phase angle is a prognostic factor for survival in amyotrophic lateral sclerosis.
AB  - Malnutrition is a well-known independent survival factor in ALS patients. Total
      body impedance analysis (BIA) has been validated for the measurement of fat-free
      mass. Another physical value obtained by BIA is phase angle (PA) that has been
      proposed to be an index of malnutrition or a survival prognostic factor in
      several diseases. We measured PA in a sample of 168 ALS patients and analysed the
      relationships between PA and neurological, respiratory and nutritional status,
      and determined whether PA is an independent prognostic factor for survival in
      ALS. BIA was performed using an Analycor3 instrument with surface electrodes at
      50 kHz and 800 microA. PA was obtained using the formula: PA =arctan (Xc/R) (in
      degrees) where Xc is the body reactance and R the bioelectric resistance.
      Relationships between quantitative variables were assessed by linear correlation
      coefficients and through univariate and multivariate linear regression analyses.
      To assess the prognostic role of PA on survival of patients, we performed
      survival analyses based on the Kaplan-Meier method using the log rank test, and
      on univariate and multivariate Cox proportional hazard model. Baseline time was
      time from multidisciplinary visit (T1) to death or censoring time. PA was always
      significantly lower in ALS patients than in healthy control subjects published in
      the literature. PA was lower in our ALS malnourished patients than in non
      malnourished patients (3.3+/-1.1 degrees versus 2.5+/-0.6 degrees , p =0.003). In
      multivariate linear regression analysis, manual muscle testing (p<0.0001), vital
      capacity (p<0.001), fat-free mass (p<0.0001), time between initial signs and T1
      (p<0.002) and age (p<0.001) were independently significantly linked with PA and
      explained 48% of PA variation. The survival of ALS patients from T1 was
      significantly linked with PA after adjustment on BMI, CV and time between initial
      signs and multidisciplinary visit, clinical form, age and sex. Patients with a PA
      <2.5 degrees had a significantly poorer survival rate than patients with a PA
      >2.5 degrees . We concluded that in ALS patients, PA is greatly decreased. It is
      related to the nutritional status of patients, and is also an independent
      prognostic factor of survival.

PMID- 18720090
TI  - Do women with polycystic ovary syndrome (PCOS) report differences in sex-typed
      behavior as children and adolescents?: Results of a pilot study.
AB  - BACKGROUND: The etiology of polycystic ovary syndrome (PCOS) is poorly
      understood, as is the impact of female hyperandrogenism on psychosocial and
      psychosexual behavior. AIM: The present study sought to test whether women with
      PCOS self-report more masculine sex-typed behavior in childhood, at adolescence,
      and as adults. SUBJECTS AND METHODS: Sixty-one women (34 women self-reporting a
      clinical diagnosis of PCOS and 27 control women not reporting a PCOS diagnosis)
      completed a questionnaire containing items on childhood sex-typed behavior,
      adolescent behavior, and present masculinity, femininity and mood. RESULTS:
      Results revealed significant differences (p<0.05) in retrospective self-reports
      of childhood sex-typed behavior and gender conformity according to PCOS status,
      with women in the PCOS group reporting less feminine childhood behavior, and less
      gender-typical behavior. A composite of sex-typed behaviors did not differ
      according to PCOS status at adolescence, although several individual items did.
      As adults, we found no differences between the groups in masculinity and
      femininity, although PCOS women reported lower happiness than controls (p<0.05),
      and trends toward a bisexual orientation and having changed sex orientation more
      often than controls (p<0.10). CONCLUSION: Results of this pilot study provide
      evidence of PCOS women self-reporting discrete psychosocial developmental
      patterns compared to non-PCOS women. These differences in retrospective self
      reported accounts may be factual or biased by current psychosocial differences,
      such as depression.

PMID- 18720091
TI  - Comparison of risk profiles between survivors and victims of sudden cardiac death
      from an acute coronary event.
AB  - AIM: This study was designed to compare the risk profiles of sudden cardiac death
      (SCD) victims and survivors of an acute coronary event. METHOD: A case-control
      study included consecutive victims of SCD (n=425) verified to be due to an acute
      coronary event at medicolegal autopsy and consecutive patients surviving an acute
      myocardial infarction (AMI) (n=644). RESULTS: Family history of SCD (odds ratio
      (OR) 1.5, 95% confidence interval (CI) 1.0-2.2, P=0.03), male gender (OR 1.8, 95%
      CI 1.3-2.4, P<0.001), current smoking (OR 2.0, 95% CI 1.5-2.6, P<0.001), cardiac
      hypertrophy (OR 3.0, 95% CI 2.3-3.9, P<0.001) and three-vessel coronary artery
      disease (CAD) (OR 5.4, 95% CI 3.6-8.2, P<0.001) were more common among the
      victims of SCD as compared to survivors of AMI. There was a cumulative increase
      of risk of being a SCD victim versus AMI survivor when more than one risk factor
      was present, with the OR rising to 44.3 (95% CI 8.0-246.7) in a current male
      smoker with a family history of SCD and cardiac hypertrophy. CONCLUSIONS: There
      are specific features that differentiate the victims of SCD from survivors of an
      acute coronary event. Clustering of several variables, such as family history of
      SCD, smoking, cardiac hypertrophy and three-vessel CAD are alarm signals of a
      very high risk of SCD.

PMID- 18720092
TI  - The power plant of the cell is also a smithy: the emerging role of mitochondria
      in cellular iron homeostasis.
AB  - Iron is required for a barrage of essential biochemical functions in virtually
      every species of life. Perturbation of the availability or utilization of iron in
      these functions or disruption of other components along iron-requiring pathways
      can not only lead to cellular/organismal insufficiency of respective biochemical
      end-products but also result in a broad derangement of iron homeostasis. This is
      largely because of the elaborate regulatory mechanisms that connect cellular iron
      utilization with uptake and distribution. Such mechanisms are necessitated by the
      'double-edged' nature of the metal, whose very property as a useful biological
      catalyst also makes it able to generate highly toxic compounds. Since the
      majority of iron is dispatched onto a functional course by mitochondria-localized
      pathways, these organelles are in an ideal position within the cellular iron
      anabolic pathways to be a central site for regulation of iron homeostasis. The
      goal of this article is to provide an overview of how mitochondria acquire and
      use iron and examine the ramifications of disturbances in these processes on
      overall cellular iron homeostasis.

PMID- 18720093
TI  - Foreign body infections due to Staphylococcus epidermidis.
AB  - Staphylococcal infections are one of the main causes of complications in patients
      with implanted foreign prosthetic material. Implants are associated with a
      significant reduction of the threshold at which contaminating Gram-positive
      bacteria, particularly Staphylococcus epidermidis, become infectious and develop
      a biofilm with phenotypic resistance to almost all antibiotics. A 1000-fold
      increase in minimal bactericidal levels against most antibiotics except rifampin
      has been repeatedly observed. Since only removal of the foreign material reverses
      these phenomena, the clinical challenge consists in finding approaches to cure
      the infection without removal of the implanted device. Rifampin combinations with
      other antibiotics, administration of exceedingly high antibiotic concentrations
      in situ, and early therapy before biofilm development are efficacious. Although
      these strategies have dramatically improved the outcome of foreign body
      infections, an improved understanding of biofilm-grown S. epidermidis is
      necessary to develop new antibacterial agents. Here, we review the pathogenesis,
      prevention, and treatment of implant infections due to S. epidermidis and
      highlight some new compounds with already promising in vitro results.

PMID- 18720094
TI  - Peters'-plus syndrome is a congenital disorder of glycosylation caused by a
      defect in the beta1,3-glucosyltransferase that modifies thrombospondin type 1
      repeats.
AB  - Genetic defects in glycosyltransferases are responsible for a number of
      developmental defects and diseases known as congenital disorders of glycosylation
      (CDGs). Peters'-plus syndrome, a rare autosomal recessive disorder, is now known
      to be a CDG. This syndrome is characterized by a specific malformation of the eye
      that includes corneal opaqueness and iridocorneal adhesions (Peters' anomaly).
      Affected individuals are short in stature and have short limbs, and may have
      cleft lip/palate, defects in the central nervous system, heart, and various other
      organs. The phenotype varies in severity, ranging from death in early childhood
      to a general delay in growth and development, and is often associated with mental
      retardation. The mutations responsible for Peters'-plus syndrome inactivate a
      beta1,3-glucosyltransferase whose function is to add a glucose moiety to O-linked
      fucose, forming a rare glucose-beta1,3-fucose disaccharide. This disaccharide
      modification is specific to thrombospondin type 1 repeats (TSRs), domains found
      in extracellular proteins that function in cell-cell and cell-matrix interactions
      and signalling. Some ninety human proteins contain TSRs, but thus far the
      disaccharide has been demonstrated on only thrombospondin 1, properdin, F
      spondin, ADAMTS-13, and ADAMTSL-1. These proteins perform essential functions in
      embryonic development, tissue remodelling, angiogenesis, neurogenesis, and
      complement activation. Identification of the beta1,3-glucosyltransferase and its
      substrate proteins is a key step towards understanding their roles in human
      development, and to uncovering the molecular and cellular mechanisms underlying
      the clinical manifestations of Peters'-plus syndrome.

PMID- 18720095
TI  - Cardiovascular health of Finnish war evacuees 60 years later.
AB  - BACKGROUND: Early life experiences might have long-term effects on health. AIM:
      To assess prevalence of cardiovascular disease and diabetes in later life among
      individuals exposed to traumatic separation in early childhood due to World War
      II. METHODS: Of the participants of the Helsinki Birth Cohort 1934-44 Study
      (n=2003), 320 had been evacuated abroad to temporary foster care in childhood.
      The remaining participants served as controls. The mean age at evacuation was 4.8
      (SD=2.4) years and the mean duration of the evacuation was 1.7 (SD=1.0) years.
      RESULTS: Cardiovascular morbidity was higher among the former war evacuees (14.7%
      versus 7.9%; odds ratio (OR)=2.0, 95% confidence interval (95% CI) 1.4-2.9;
      P<0.001). A similar difference in prevalence of type 2 diabetes was observed
      (19.7% versus 14.8%; OR=1.4, 95% CI 1.1-1.9, P=0.025). The former war evacuees
      were also more likely to be hypertensive (P<0.05). The effects on morbidity were
      not explained by age at testing or socio-economic circumstances in childhood or
      adulthood. CONCLUSION: Early life traumatic events may extend lifelong effects on
      health. This study is among the first to show that early life trauma predicts
      higher prevalence of cardiovascular disease and type 2 diabetes in late
      adulthood, in a longitudinal clinical study setting.

PMID- 18720096
TI  - Prevention of calcific aortic valve stenosis-fact or fiction?
AB  - Valve replacement is the only long-term effective treatment for calcific aortic
      valve stenosis. However, this treatment is aimed only at patients with advanced
      leaflet disease and symptoms of left ventricular obstruction. Over the past 15
      years, our understanding of the pathogenesis of calcific aortic stenosis has
      changed significantly: away from a passive degenerative disease to an active
      process involving endothelial dysfunction, lipid accumulation, an inflammatory
      infiltrate, and a regulated process of calcification. Since many of the same
      processes are characteristic of atherosclerosis, trials have been undertaken to
      test whether medical therapy (statins, renin-angiotensin inhibition) can prevent
      or alter the disease course. Although retrospective and non-randomized studies
      suggested a positive effect with statins, benefit has not been seen in
      perspective randomized controlled trials, although two major studies are still in
      progress. Inhibition of renin-angiotensin has shown discordant results in
      retrospective studies with no randomized controlled data published. In the
      future, we need to consider other medical therapies that might target different
      pathways in this disease process. In addition, we need to define the optimal
      timing and duration of therapy for this chronic slowly progressive disease;
      treatments aimed at the early disease process may be ineffective with end-stage
      tissue changes.

PMID- 18720097
TI  - Forensic mental health orders: orders without borders.
AB  - OBJECTIVE: Persons subject to forensic mental health orders imposed by the courts
      form a small but politically salient group. Their management provides a number of
      challenges for mental health services and for governments throughout Australia.
      Although their overall management has been enhanced by recent developments in
      forensic services, there is a lack of consistent cross-border agreements between
      states and territories. This paper will discuss how this situation is not
      conducive to effective risk management and is a denial of patients' legitimate
      demands for freedom of movement. A proposal for the adoption of appropriate
      principles to improve the current state of affairs is outlined. CONCLUSION:
      Legislative reform is required to ensure the safe and ethical management of
      mentally disordered offenders subject to forensic mental health orders in
      Australia.

PMID- 18720098
TI  - Detection of protein biomarkers using high-throughput immunoblotting following
      focal ischemic or penetrating ballistic-like brain injuries in rats.
AB  - PRIMARY OBJECTIVE: Recent efforts have been aimed at developing a panel of
      protein biomarkers for the diagnosis/prognosis of the neurological damage
      associated with acute brain injury. METHODS AND PROCEDURES: This study utilized
      high-throughput immunoblotting (HTPI) technology to compare changes between two
      animal models of acute brain injury: penetrating ballistic-like brain injury
      (PBBI) which mimics the injury created by a gunshot wound and transient middle
      cerebral artery occlusion (MCAo) which is a model of stroke. Brain and blood were
      collected at 24-hours post-injury. MAIN OUTCOMES AND RESULTS: This study
      identified the changes in 18 proteins following PBBI and 17 proteins following
      MCAo out of a total of 998 screened proteins. Distinct differences were observed
      between the two models: five proteins were up- or down-regulated in both models,
      23 proteins changed in only one model and one protein was differentially
      expressed. Western blots were used to verify HTPI results for selected proteins
      with measurable changes observed in both blood and brain for the proteins STAT3,
      Tau, PKA RII beta, 14-3-3 epsilon and p43/EMAPII. CONCLUSIONS: These results
      suggest distinct post-injury protein profiles between brain injury types
      (traumatic vs. ischemic) that will facilitate strategies aimed at the
      differential diagnosis and prognosis of acute brain injury.

PMID- 18720099
TI  - Medical complications, physical function and communication skills in patients
      with traumatic brain injury: a single centre 5-year experience.
AB  - OBJECTIVE: The aim of this retrospective study was to review the medical
      complications of patients with traumatic brain injury (TBI) who were followed in
      2000-2006. METHODS AND PROCEDURES: The demographic data, functional and cognitive
      status of 116 persons with TBI were noted. The presence of communication
      problems, swallowing disturbances, urinary and faecal incontinence, pressure
      ulcer, deep venous thrombosis (DVT), post-traumatic seizure (PTS) and heterotopic
      ossification (HO) were recorded at first admission and follow-up. MAIN OUTCOME
      AND RESULTS: This study detected aphasia in 19.0%, dysarthria in 30.2%, dysphagia
      in 17.2%, pressure ulcers in 6.9% and DVT in 2.6% the our patients with TBI.
      Urinary and faecal incontinence on admission were 32.7% and 26.7%, respectively.
      Patients with incontinence had poorer cognitive function than those with normal
      continence. HO rate was 18.1% and the ambulation levels of patients with HO were
      worse than those without HO. PTS was seen in 13.8% of the patients on admission
      and this ratio increased to 21.6% during the follow-up. In these patients, the
      aetiological risk factors for PTS were gunshot and fall injuries. CONCLUSIONS:
      Considering the wide spectrum of complications, this study advocates that these
      persons with TBI should be followed promptly by a multidisciplinary team.

PMID- 18720100
TI  - Individuals with autism can categorize facial expressions.
AB  - The ability of high-functioning individuals with autism to perceive facial
      expressions categorically was studied using eight facial expression continua
      created via morphing software. Participants completed a delayed matching task and
      an identification task. Like undergraduate male participants (N = 12),
      performance on the identification task for participants with autism (N = 15) was
      predicted by performance on the delayed matching task for the angry-afraid, happy
      sad, and happy-surprised continua. This result indicates a clear category
      boundary and suggests that individuals with autism do perceive at least some
      facial expressions categorically. As this result is inconsistent with findings
      from other studies of categorical perception in individuals with autism, possible
      explanations for these findings are discussed.

PMID- 18720101
TI  - Developmental and sex-related differences in preschoolers' affective decision
      making.
AB  - This study investigated developmental and sex-related differences in affective
      decision making, using a two-deck version of Children's Gambling Task
      administered to 3- and 4-year-old children. The main findings were that 4-year
      old children displayed better decision-making performance than 3-year-olds. This
      effect was independent of developmental changes in inductive reasoning, language,
      and working memory. There were also sex differences in decision-making
      performance, which were apparent only in 3-year-old children and favored girls.
      Moreover, age predicted awareness of task and the correlation between the latter
      and decision-making performance was significant, but only in 4-year-old children.
      This study thus indicates that there is a remarkable developmental leap in
      affective decision making, whose effects are apparent around the age of 4, which
      according to our results, also marks the age when the correlation of declarative
      knowledge and decision-making performance becomes significant.

PMID- 18720102
TI  - Training of familiar face recognition and visual scan paths for faces in a child
      with congenital prosopagnosia.
AB  - In the current report we describe a successful training study aimed at improving
      recognition of a set of familiar face photographs in K., a 4-year-old girl with
      congenital prosopagnosia (CP). A detailed assessment of K.'s face-processing
      skills showed a deficit in structural encoding, most pronounced in the processing
      of facial features within the face. In addition, eye movement recordings revealed
      that K.'s scan paths for faces were characterized by a large percentage of
      fixations directed to areas outside the internal core features (i.e., eyes, nose,
      and mouth), in particular by poor attendance to the eye region. Following
      multiple baseline assessments, training focused on teaching K. to reliably
      recognize a set of familiar face photographs by directing visual attention to
      specific characteristics of the internal features of each face. The training
      significantly improved K.'s ability to recognize the target faces, with her
      performance being flawless immediately after training as well as at a follow-up
      assessment 1 month later. In addition, eye movement recordings following training
      showed a significant change in K.'s scan paths, with a significant increase in
      the percentage of fixations directed to the internal features, particularly the
      eye region. Encouragingly, not only was the change in scan paths observed for the
      set of familiar trained faces, but it generalized to a set of faces that was not
      presented during training. In addition to documenting significant training
      effects, our study raises the intriguing question of whether abnormal scan paths
      for faces may be a common factor underlying face recognition impairments in
      childhood CP, an issue that has not been explored so far.

PMID- 18720103
TI  - "Fragment errors" in deep dysgraphia: further support for a lexical hypothesis.
AB  - In addition to various lexical errors, the writing of patients with deep
      dysgraphia may include a large number of segmental spelling errors, which
      increase towards the end of the word. Frequently, these errors involve deletion
      of two or more letters resulting in so-called "fragment errors". Different
      positions have been brought forward regarding their origin, including rapid decay
      of activation in the graphemic buffer and an impairment of more central (i.e.,
      lexical or semantic) processing. We present data from a patient (M.D.) with deep
      dysgraphia who showed an increase of segmental spelling errors towards the end of
      the word. Several tasks were carried out to explore M.D.'s underlying functional
      impairment. Errors affected word-final positions in tasks like backward spelling
      and fragment completion. In a delayed copying task, length of the delay had no
      influence. In addition, when asked to recall three serially presented letters, a
      task which had not been carried out before, M.D. exhibited a preference for the
      first and the third letter and poor performance for the second letter. M.D.'s
      performance on these tasks contradicts the rapid decay account and instead
      supports a lexical-semantic account of segmental errors in deep dysgraphia. In
      addition, the results fit well with an implemented computational model of deep
      dysgraphia and segmental spelling errors.

PMID- 18720104
TI  - Carbon monoxide poisoning in Jerusalem: epidemiology and risk factors.
AB  - OBJECTIVES: To describe the epidemiology of carbon monoxide (CO) poisoning in
      Jerusalem and identify risk factors for such poisoning. DESIGN: A retrospective
      descriptive analysis of patients with CO poisoning who presented to the Hadassah
      hospitals in Jerusalem from 1994 to 2006. PATIENTS: All patients with suspected
      CO poisoning were examined and those with confirmed cases [carboxyhemoglobin
      (COHb) level >5%] were included. Sources of exposure, seasonal variation, and
      demographic characteristics were analyzed. RESULTS: There were 292 patients (49%
      males) with 40 family clusters that accounted for 149 patients (51%); 230
      patients (79%) presented during the winter months. All but one had unintentional
      CO intoxication. The main sources of exposure were faulty gas heaters (n = 135),
      fire (n = 102), and other residential heating systems (n = 40). The estimated
      annual incidence of CO poisoning decreased from 6.45 per 100,000 in 1994-2000 to
      3.53 per 100,000 in 2001-2006. High-risk intoxication (COHb level >25%) occurred
      in 84 patients (29%). Factors associated with severe intoxication were male
      gender, individual patients (compared with those in clusters), and faulty gas
      heaters (compared with other sources). CONCLUSIONS: Males exposed to CO may have
      a more severe intoxication. The lower risk in patients presenting in clusters
      could be explained by the assumption that severe presentation in one patient
      alerts the others who are less severely affected. The implementation of safer
      standards for residential heating systems and CO detectors together with the
      public education may explain the decline in the incidence of CO poisoning.

PMID- 18720105
TI  - A systematic comparison of the actual, potential, and theoretical health effects
      of cobalt and chromium exposures from industry and surgical implants.
AB  - Humans are exposed to cobalt (Co) and chromium (Cr) from industry and surgical
      devices, most notably orthopedic joint replacements. This review compares the
      potential health effects of exposure to Co and Cr contaminants from these two
      different sources, both in the locally exposed tissues and at sites distant to
      the primary exposure. Surgical implantation results largely in exposures to ions,
      corrosion products, and particles of Co and Cr. Industrial exposures are
      predominantly to metal compounds and particles. Although there are large
      literatures on industrial and surgical exposures to these metals, there has yet
      to be a systematic comparison of the two to test whether more general lessons
      might be learned about the human toxicology of Co and Cr. Both industrial and
      surgical exposures cause inflammatory and other immune reactions in the directly
      exposed tissues. In the lung there is a well-established risk of cancer following
      long-term exposures to hexavalent Cr; however, the development of sarcoma in the
      connective tissues adjacent to implants in response to metal particles is rare.
      Both types of exposure are associated with changes in the peripheral blood,
      including evidence of oxidative stress, and altered numbers of circulating immune
      cells. There is dissemination of Co and Cr to sites distant to the orthopedic
      implant, but less is known about systemic dissemination of these metals away from
      the lung. The effects of industrial exposures in the reproductive, renal, and
      cardiac systems have been investigated, but this has yet to be explored after
      surgical exposures. The form of the metal (and associated elements) in both
      instances is key to the toxicological effects arising in the body and further
      characterization of debris released from devices is certainly recommended, as is
      the impact of nanotoxicology on the health and safety of workers and patients.
      Biomonitoring schemes currently used in industry could be translated, if
      required, into suitable programs for orthopedic out-patients. Cross-communication
      between experts in industrial and occupational medicine and regulatory agencies
      may be useful.

PMID- 18720106
TI  - Outcome of treatment of the mismanaged pediatric elbow trauma: a series of 73
      cases.
AB  - PURPOSE: To analyze the outcome of the management of pediatric elbow trauma
      referred to our hospital after initial intervention by traditional bone setters.
      METHOD: Retrospective study of 73 patients, presenting to the hospital with a
      complication attributable to the initial mismanagement of their injuries.
      RESULTS: The mode of presentation was directly related to the type of initial
      intervention on the basis of which we were able to quantify bone setters into two
      groups. The first group using a rather rough method of trauma treatment involving
      the application of tight local bandages, massage and manipulation and a second
      group having a relatively less rough approach, applying splints to the injured
      extremity without tight bandages and manipulation. The result of treatment of
      these injuries was determined by the delay in presentation and the type of
      injury. CONCLUSION: This study highlights the importance of dealing with the
      unchecked and unsupervised practice of bone setting in the developing world. We
      believe that training these people on the pattern of traditional birth attendants
      can at the very least lower the occurrence, if not entirely eliminate the problem
      of mismanaged trauma in this part of the world.

PMID- 18720107
TI  - Risk assessment and management for providers of community-based rehabilitation to
      people with acquired brain injury: health professionals' perspectives.
AB  - PURPOSE: This study aimed to explore health professionals' perspectives regarding
      the presence, assessment and management of risks when providing community-based
      rehabilitation (CBR) to clients with acquired brain injury (ABI). METHOD: A
      qualitative approach using semi-structured interviews of health professionals
      working in CBR. RESULTS: The main themes were: (1) risk assessment in CBR
      settings is an informal, unstructured, complex, multi-phase and cyclical process
      extending over a period of time; (2) structured and standardised risk assessments
      were not considered ideal for use in CBR services catering for people with ABI;
      (3) CBR services face numerous challenges in providing effective risk assessment
      and management; (4) the risks encountered by health professionals in CBR settings
      are not always predictable or preventable; and (5) CBR risk management focuses on
      implementing a range of practical strategies. CONCLUSIONS: A flexible risk
      assessment process supported by a range of practical risk management strategies
      to minimise and manage potential risks is advocated by health professionals
      working in CBR services for people with ABI. There is a need for more research
      into the effectiveness of current risk assessment and management strategies for
      CBR services.

PMID- 18720108
TI  - 'We need to be the centrepiece': adults with cerebral palsy and complex
      communication needs discuss the roles and needs of family carers in hospital.
AB  - PURPOSE: The aim of this study was to explore the perceptions of adults with
      cerebral palsy and complex communication needs (CCN) on the roles and needs of
      their family carers in hospital. METHOD: As part of a larger study we conducted
      one focus group with six adults with cerebral palsy and CCN who participated in
      the group using a variety of augmentative and alternative communication methods.
      RESULTS: Participants explored why and how family carers become involved in care
      in hospital, what this care involves, and how this impacts upon themselves as
      patients and on their family carers. Reasons underlying their dependence upon
      family carers during a hospital stay were outlined, particularly the carer's role
      in communication, information exchange and access to essential daily care.
      Strategies to improve the experience for family carers in hospital were
      discussed. CONCLUSION: Involvement of family carers of people with cerebral palsy
      and CCN during an inpatient hospital stay is complex. Although they depend upon
      others for communication support, these individuals with CCN wish to be treated
      as adults in hospital and included in decisions about their healthcare. They want
      to be involved in the education of hospital staff, and to communicate directly
      with hospital staff.

PMID- 18720109
TI  - Cross-cultural adaptation of the Brazilian-Portuguese version of the Cumberland
      Ankle Instability Tool (CAIT).
AB  - PURPOSE: To develop and psychometrically test a Brazilian-Portuguese version of
      the Cumberland Ankle Instability Tool (CAIT), the only questionnaire that
      provides a numeric measure for functional ankle instability. METHODS: The CAIT
      was translated and adapted into Brazilian-Portuguese according to the Guidelines
      for the process of cross-cultural adaptation of self report measures. The
      Brazilian-Portuguese version of the CAIT was tested for internal consistency,
      test-retest reliability, ceiling and floor effects and responsiveness in 131
      participants. Participants were recruited from the general community in Brazil (N
      = 101, community group) and from those seeking treatment for an ankle sprain from
      2 clinics in Brazil (N = 30, treatment group). RESULTS: The Brazilian-Portuguese
      version of the CAIT had high internal consistency (Cronbach alpha = 0.86 for
      right ankles and 0.88 for left ankles), reliability (ICC = 0.95, 95% CI 0.93
      0.97); and good responsiveness (ES = 0.75, 95% CI 0.49-1.00). No ceiling or floor
      effects were observed. CONCLUSIONS: The Brazilian-Portuguese version of the CAIT
      is as reliable as the English version of the questionnaire, has high internal
      consistency and good responsiveness. It thus provides the first tool that can be
      used to assess functional ankle instability by clinicians and researchers working
      among Brazilian-Portuguese speakers.

PMID- 18720110
TI  - Time out based discipline strategy for children's non-compliance with cystic
      fibrosis treatment.
AB  - PURPOSE: To evaluate a time out based discipline strategy designed to decrease
      treatment avoidance in children with cystic fibrosis (CF) who displayed non
      compliant behaviour to their parents' treatment requests. METHOD: A single
      subject reversal design was used to compare baseline compliance when a time out
      based discipline strategy was in effect. Outcome measures included observational
      assessments of compliance, parent ratings of child treatment-related behaviour
      problems and parent reported preference for the time out strategy. RESULTS:
      Greater compliance was demonstrated when the time out strategy was in place.
      Parents reported fewer treatment-related behaviour problems and desired less
      professional help for these problems upon completion of the study and reported
      preferring the time out discipline strategy to their typical child management
      strategy. CONCLUSIONS: This discipline strategy represents a practical and
      appealing brief intervention that is shown to help parents maximise their
      children's participation in life-extending treatments. This intervention
      minimises the need for parent-therapist interaction, which may be of particular
      importance to families of patients with CF who already devote significant time to
      medical appointments and interventions. The preliminary nature of this data and
      lack of reversal for one of the participants emphasise the need for additional
      research to replicate the findings.

PMID- 18720111
TI  - Pre prosthetic mobility: the amputees' perspectives.
AB  - PURPOSE: It is considered good practice that amputees remain in a wheelchair
      until fitted with a prosthesis. However, this practice is not evidence based. In
      the first of a series of studies in pre prosthetic mobility, this study will
      explore the individual amputees' perspective. METHOD: A total of 25 participants
      from a regional disablement service centre were interviewed focusing on their
      experiences of getting around the home post discharge. The transcripts were coded
      for types of mobility methods used and the content analysed. RESULTS: Whilst the
      wheelchair was the predominant method of mobilizing, this was not viewed
      positively by amputees. Crutches were frequently used, even if crutches were not
      provided by therapists. Participants cited space and choice as reasons behind
      this, in particular the psychological impact of being 'stuck' in a wheelchair.
      Other methods cited included crawling and bottom shuffling. CONCLUSION: Amputees
      do not always comply with therapists' advice and frequently use other methods of
      mobilizing as a matter of choice as well as necessity. The risk factors
      associated with these methods is a priority for future research.

PMID- 18720112
TI  - Testing a home-telehealth programme for US veterans recovering from stroke and
      their family caregivers.
AB  - PURPOSE: The study purpose was to implement a stroke-specific, care coordination
      home telehealth (CCHT) programme for US veterans with stroke and their family
      caregivers. METHODS: In a non-randomized open trial using a mixed methods design,
      we tested the utility of a stroke-specific, home telehealth programme with 18
      veterans and 14 caregivers for 14 days. Programme questions assessed physical
      impairment, depressive symptoms, and fall prevalence among veterans, and burden
      level among family caregivers. Nine veterans and six caregivers completed post
      programme interviews exploring their experiences with telehealth. RESULTS: During
      the 14-day trial, 55% of the veterans screened positive for depression at least
      once, 36% of the caregivers had clinically significant burden, half of the
      veterans and caregivers reported post-stroke concerns, and 90% believed post
      stroke contact from a care coordinator would have been helpful. In the
      interviews, seven veterans indicated they had fallen or almost fallen post
      stroke. Themes centred on tailoring CCHT to individual needs, coordinating with
      support services, identifying safety issues, and providing information about
      stroke prevention. CONCLUSIONS: Home telehealth offers innovative ways to target
      post-stroke rehabilitation programmes to the needs and concerns of patients and
      their caregivers, and should include regular real-time contact between stroke
      patients and their healthcare providers.

PMID- 18720113
TI  - Post-stroke recovery of high-level cognitive function.
AB  - This research explored the post-stroke cognitive ability of a 52-year male, KM,
      who suffered a left middle cerebral artery stroke. KM received no rehabilitation
      post-stroke, as clinic assessments suggested that mental functioning had returned
      to an acceptable level. However, KM believed that his cognitive ability had not
      returned to pre-stroke levels. Comparisons with pre-stroke data from an unrelated
      study and additional testing using sensitive cognitive measures supported his
      observations. This research concludes that patient observations and more
      sensitive testing of post-stroke cognitive functioning may reveal additional high
      level cognitive deficits.

PMID- 18720114
TI  - Functional characteristics of children diagnosed with Childhood Apraxia of
      Speech.
AB  - PURPOSE: The purpose of this study was to describe the complex array of
      functional problems in children diagnosed by their treating speech/language
      pathologist with Childhood Apraxia of Speech (CAS), a poorly understood, severe
      speech sound disorder. METHOD: We asked parents (n = 201) attending the first
      national parent conference on CAS to voluntarily complete a survey, which
      evaluated 43 functional domains from the International Classification of
      Functioning, Disability, and Health-Children and Youth version (ICF-CY). The
      survey also included questions about co-existing medical, developmental, and
      mental health conditions and about service utilization. Data were analyzed using
      descriptive statistics and exploratory factor analysis. RESULTS: The most
      prevalent functional problems in addition to communication were attention
      (focus), vestibular function, temperament, fine hand use, maintaining attention,
      and learning to write. Four orthogonal factors accounted for 23% of the variance
      in functional problems: Cognitive and Learning Problems, Social Communication
      Difficulties, Behavioral Dysregulation, and Other Oral Motor Problems. Over half
      the sample had health, mental health, and developmental conditions. Almost all of
      the children used early intervention and speech/language therapy services.
      CONCLUSIONS: The ICF-CY provided a systematic approach for describing and
      categorizing functional problems in children with CAS. The identified factors
      should guide the multidisciplinary team in conducting comprehensive evaluations,
      rehabilitation, and long-term follow-up of children with CAS.

PMID- 18720115
TI  - Interactive drama in complex neurological disability management.
AB  - PURPOSE: To establish whether interactive drama has any effect on the responses
      of people with complex neurological disabilities resident in a long term care
      facility. METHOD: This was a service evaluation using interviews with a group of
      31 independently consenting long term care residents, and 27 staff, and
      observations of engagement of 74 residents involved in an Interactive Drama
      Project (92.4% of those who had the opportunity to participate). RESULTS: Twenty
      five (81%) of the 31 residents interviewed reported a new atmosphere of community
      spirit, 29 (93%) enjoyed the rehearsals, 28 (90.5%) reported a state of 'flow'
      and 17 (54.6%) a perception of achievement. Fifteen (55.7%) of the 27 staff who
      completed questionnaires felt that the project had had a positive effect on staff
      resident relationship. Twenty (64.4%) residents and 14 (51.7%) staff reported
      learning something new about others. CONCLUSIONS: The majority of participants
      with complex neurological disabilities were able to engage with interactive drama
      for some of the time. Therefore interactive drama offered residents opportunities
      for enjoyment, achievement, challenge and experiencing meaningful occupations.

PMID- 18720116
TI  - VISA-P score for patellar tendinopathy in males: adaptation to Italian.
AB  - PURPOSE: To translate and adapt the English VISA-P questionnaire to Italian and
      to perform reliability and validity evaluations of the Italian VISA-P version in
      patients with patellar tendinopathy. METHODS: The VISA-P English version was
      translated into Italian by a bilingual orthopaedic surgeon. The back translation
      of the Italian version into English was performed by another bilingual
      orthopaedic surgeon. The original version was compared with the back translation.
      The VISA-P-I questionnaire was then administered to 25 male athletes (average age
      27.9, range 18-32 years) with a diagnosis of patellar tendinopathy. For test
      retest evaluation, the 25 patients were asked to complete the questionnaire at
      first examination, and 30 minutes following the end of this examination. RESULTS:
      The kappa statistics for 25 patients was 0.78. There were no significant
      differences between the scores immediately after the consultation and 30 minutes
      later. CONCLUSIONS: Italian and the English versions of the VISA-P questionnaire
      evaluate the same aspects of clinical severity in patients with patellar
      tendinopathy.

PMID- 18720117
TI  - Using community/researcher partnerships to develop a culturally relevant
      intervention for children with communication disabilities in Kenya.
AB  - PURPOSE: The objective of this study is to develop a culturally relevant
      community-based intervention for children with communication disabilities in
      Kenya through a community/researcher partnership. The resulting intervention is
      for use in a randomized control trial which will be reported at a later stage.
      METHOD: Using a qualitative approach, initial data was collected through focus
      group discussions with women, disabled people and traditional dancers. The groups
      examined the needs, problems and challenges faced by disabled children and their
      families. This generated the content and structure for a series of participatory
      workshops with a further two women's groups. These workshops strove to generate a
      culturally relevant community-based intervention programme for children with
      communication disabilities and their families. The content and balance of the
      resulting intervention was observed to be different from existing programmes
      described in the literature. Notably it included many culturally appropriate
      strategies for increasing social integration and raising community awareness.
      RESULTS: The process of generating a locally relevant community-based
      rehabilitation intervention is potentially transferable and has particular
      relevance to the estimated 80% of the world where there are no formal
      rehabilitation services for children with disabilities and where women's groups
      are a strong element of local culture. CONCLUSION: (i) Community/researcher
      partnerships can be used to develop interventions; (ii) such interventions are
      different from those imported from other cultures; and (iii) this process is
      transferable and can be part of the preparations for a Randomized Control Trial.

PMID- 18720118
TI  - A systematic review of clinical outcomes, clinical process, healthcare
      utilization and costs associated with telerehabilitation.
AB  - PURPOSE: To identify clinical outcomes, clinical process, healthcare utilization
      and costs associated with telerehabilitation for individuals with physical
      disabilities. METHOD: Relevant databases were searched for articles on
      telerehabilitation published until February 2007. Reference lists were examined
      and key journals were hand searched. Studies that included telerehabilitation for
      individuals with physical impairments and used experimental or observational
      study designs were included in the analysis, regardless of the specific clientele
      or location of services. Data was extracted using a form to record methodological
      aspects and results relating to clinical, process, healthcare utilization and
      cost outcomes. Study quality of randomized clinical trials was assessed using the
      PEDro rating scale. RESULTS: Some 28 articles were analysed. These dealt with
      rehabilitation of individuals in the community, neurological rehabilitation,
      cardiac rehabilitation, follow-up of individuals with spinal cord injuries,
      rehabilitation for speech-language impairments, and rehabilitation for varied
      clienteles. Clinical outcomes were generally improved following a
      telerehabilitation intervention and were at least similar to or better than an
      alternative intervention. Clinical process outcomes, such as attendance and
      compliance, were high with telerehabilitation although few comparisons are made
      to alternative interventions. Consultation time tended to be longer with
      telerehabilitation. Satisfaction with telerehabilitation was consistently high,
      although it was higher for patients than therapists. Few studies examined
      healthcare utilization measures and those that did reported mixed findings with
      respect to adverse events, use of emergency rooms and doctor visits. Only five of
      the studies examined costs. There is some preliminary evidence of potential cost
      savings for the healthcare facility. CONCLUSION: While evidence is mounting
      concerning the efficacy and effectiveness of telerehabilitation, high-quality
      evidence regarding impact on resource allocation and costs is still needed to
      support clinical and policy decision-making.

PMID- 18720119
TI  - Development of a questionnaire assessing work-related stress in women -
      identifying individuals who risk being put on sick leave.
AB  - PURPOSE: To develop a self-administered questionnaire assessing work-related
      stress in women, aiming to identify individuals that risk long-term sick leave,
      and to evaluate the reliability of the questionnaire. METHOD: The study was
      carried out in two phases. The initial phase was to construct the questionnaire
      and to confirm its face validity. The second phase was to test the reliability of
      the questionnaire. RESULTS: The questionnaire was constructed from an empirical
      standpoint and based on a qualitative study. Two main themes were identified: One
      was related to factors at work and the other to the persons themselves. Eight
      categories were recognized from these themes and questions were constructed. A
      pilot group confirmed the validity of the questions. A first version of the
      questionnaire was subjected to test-retest analysis and all unstable items were
      improved. The reliability of the revised version was satisfactory. CONCLUSIONS: A
      simple questionnaire, containing 20 questions assessing work-related stress in
      women, with the purpose of identifying individuals that risk long-term sick leave
      was developed. The questionnaire was found to have good face validity and high
      reliability. Since there is a need for preventive methods in identifying
      individuals that risk being put on sick leave, this questionnaire can be a useful
      tool for health professionals.

PMID- 18720120
TI  - Biomechanics of the Achilles tendon.
AB  - PURPOSE: Tendons behave viscoelastically and exhibit adaptive responses to
      conditions of increased loading and disuse. Strain patterns in tendons may not be
      uniform, as tendons show stress-shielded areas and areas subjected to compressive
      loading at the enthesis. These areas correspond to the sites where tendinopathic
      characteristics are typically seen. METHOD: We review the biomechanic literature
      on Achilles tendon, trying to interpret it on the basis that classic inflammatory
      changes are not frequently seen in chronic athletic tendon conditions. RESULTS:
      Biomechanical studies show that the strains within the tendons near their
      insertion site are not uniform. If the material properties are similar throughout
      the tendon, forces transferred through the insertion site preferentially load the
      side of the tendon that is usually not affected initially in tendinopathy. In
      that case, the side affected by tendinopathy is generally 'stress shielded'.
      CONCLUSION: The presence of differential strains opens the possibility of
      alternative biomechanical explanations for the pathology found in these regions
      of the tendon. The traditional concept of tensile failure may not be the
      essential feature of the pathomechanics of insertional tendinopathy. Additional
      work is needed ascertain whether such principles should be incorporated in
      current rehabilitation.

PMID- 18720122
TI  - Community ambulation: environmental impacts and assessment inadequacies.
AB  - BACKGROUND: Community ambulation is an important goal for both clients and health
      professionals yet it is an outcome only variously achieved by clients discharged
      from rehabilitation settings back into their community. OBJECTIVE: To review the
      available literature about the assessment tools that are currently used to
      determine community ambulation status and to determine from an evaluation of
      these tools the effectiveness of the evaluation when compared to known
      environmental dimensions that impact on ambulation in the community. METHOD: A
      review of published papers from English language literature using CINAHL,
      ProQuest, Medline and other databases was conducted. RESULTS: Only eight papers
      were found in the literature to inform health professionals about the impact of
      the environment on community ambulation. No current mobility assessment tools
      were identified that assess all the environmental demands that can impact on the
      activity of community ambulation. From the tools reviewed the most frequently
      evaluated environmental mobility dimensions were walking distance and time
      constraints. CONCLUSIONS: Health professionals need assessment tools that
      evaluate the impact of the environment on an individual's mobility in order to
      determine community ambulation status. The literature to date provides little
      guidance about the impact of the environment and current evaluation tools are
      limited in clinical usefulness with respect to the depth and breadth of
      information gained.

PMID- 18720121
TI  - Eccentric exercises for the management of tendinopathy of the main body of the
      Achilles tendon with or without the AirHeel Brace. A randomized controlled trial.
      A: effects on pain and microcirculation.
AB  - PURPOSE: To compare eccentric training and the combination of eccentric training
      with the AirHeel Brace for the management of tendinopathy of the main body of the
      Achilles tendon. METHODS: We recruited 116 subjects with unilateral tendinopathy
      of the main body of the Achilles tendon, who were randomized in two groups. Group
      A performed a regimen of daily eccentric training associated with the AirHeel
      Brace (Donjoy Orthopedics, Vista, CA, USA). Group B performed the same eccentric
      training without the AirHeel Brace. Tendon microcirculatory mapping was performed
      using combined Laser-Doppler and spectrophotometry. Pre- and post-operative FAOS
      score and VAS score were used to evaluate the patients. RESULTS: The FAOS score
      and the VAS score showed significant improvements from pre-operative to post
      operative values in both groups (A 5.1 +/- 2 vs. 2.9 +/- 2.4, 43% reduction and
      B: 5.4 +/- 2.1 vs. 3.6 +/- 2.4, 33% reduction, both p = 0.0001). There were no
      statistically significant differences in FAOS score and VAS score when comparing
      the two groups after the end of the intervention. In Group A, tendon oxygen
      saturation in the main body of the Achilles tendon showed significant increase
      from pre- to post-management values (68 +/- 12 vs.74 +/- 8%, p = 0.003). Post
      capillary venous filling pressures showed significant reduction from pre- to post
      intervention values. CONCLUSION: Eccentric training, associated or not with the
      AirHeel Brace, produces the same effect in patients with tendinopathy of the main
      body of the Achilles tendon. The combination of eccentric training with the
      AirHeel Brace can optimize tendon microcirculation, but these micro-circulator
      advantages do not translate into superior clinical performance when compared with
      eccentric training alone.

PMID- 18720123
TI  - Tendon repair through stem cell intervention: cellular and molecular approaches.
AB  - Tendon injuries are common in either the workplace or sport activities, with some
      3 to 5 million tendon and ligament injuries occurring annually worldwide.
      Management of tendon injury currently follows two routes: Conservative
      (rehabilitation and pain relief), or surgical. Irrespective of which of these
      primary treatment routes are followed, even if healing does occur, it may not
      result in a full gain of function. The inability of the tendon to self-repair and
      the relative inefficiency of current treatment regimens suggest that identifying
      alternative strategies is a priority. One such alternative is the use of stem
      cells to repair damage, either through direct application or in conjunction with
      scaffolding. We describe the current state of the art in terms of: (i) Molecular
      markers of tendon development, (ii) stem cell applicability to human tendon
      repair, (iii) scaffolding for in vitro tendon generation, and (iv)
      chemical/molecular approaches to both induce stem cell differentiation into
      tenocytes and maintain their proliferation in vitro.

PMID- 18720124
TI  - Connecting with clinicians: opportunities to strengthen rehabilitation research.
AB  - PURPOSE: This article examines the distinctive opportunities and challenges
      involved in connecting with clinicians to strengthen rehabilitation research.
      METHOD: The relevant literature on various factors that link researchers and
      clinicians is summarized and discussed. RESULTS: Links between researchers and
      clinicians are demonstrated by evidence-based practice, common conceptual
      background and the development of research capacity. Sustainable partnerships can
      evolve throughout the research process by using various enduring strategies such
      as experts' committee as well as novel approaches like communities of practice.
      CONCLUSION: This paper reflects the conviction that reducing the gap between
      research and clinical practice will be facilitated by implementing partnerships
      originating from both researchers and clinicians.

PMID- 18720125
TI  - Is there a scientific basis for pet therapy?
AB  - PURPOSE: Pet therapy is a non-pharmacological intervention, but its scientific
      value is still undefined. METHODS: The first step to identify the papers of
      interest was the access to the MEDLINE library from 1960 until June 2007 and the
      Cochrane controlled trials registry. RESULTS: At present there is consistent
      evidence of the protective effect against cardiovascular risk, mainly through the
      moderate exercise prompted by walking a dog. Indeed, walking a dog may contribute
      to a physically active lifestyle. Moreover, patients suffering from chronic
      illness are likely to benefit from pet companionship. CONCLUSIONS: There is a
      contrast between physical effects (for which the evidence is fairly clear) and
      the psychological benefits (for which the evidence is controversial). Further
      randomised researches are necessary to convey scientific dignity to the human -
      animal relationship.

PMID- 18720126
TI  - Achilles tendon ossification: pathology, imaging and aetiology.
AB  - BACKGROUND: We report a patient with ossification of the Achilles tendon,
      presenting plain radiographs, ultrasound, power doppler, computed tomography and
      magnetic resonance findings. The majority of the tendon was ossified, and there
      was adjacent soft tissue oedema. The appearance of peritendinous oedema
      associated with ossification has not, to our knowledge, been reported in the
      literature, and could account for hindfoot pain in cases of tendon ossification.
      METHOD: A review of 44 articles on aetiology, histology and imaging was
      performed. RESULTS: Trauma, either accidental or from surgery, rather than
      tendinopathy is the likely aetiological factor. CONCLUSION: The Achilles tendon
      usually responds to an insult with the development of mature bone, not dystrophic
      calcification, with no evidence of inflammatory or degenerative changes.

PMID- 18720127
TI  - Comparing the self concept of children with cerebral palsy to the perceptions of
      their parents.
AB  - PURPOSE: Understanding self concept is important for therapists treating children
      with cerebral palsy because knowing what children and parents think about
      perceived competencies and adequacies can be taken into account in determining
      treatment goals. This study investigated: (i) If differences existed between the
      self concept ratings of children with cerebral palsy compared to their parent's
      perception of their child's abilities and attributes, and (ii) the strength of
      association between the child and parent ratings. METHOD: Thirty children (14
      females, 16 males; mean age 11 years 5 months, SD 2 years 6 months, range 8-16
      years) with spastic hemiplegia or diplegia and gross motor skills classified as
      level I or II on the Gross Motor Function Classification System rated their self
      concept using the Self-Perception Profile for Children questionnaire. Their
      parents completed the accompanying Parent Rating Scale. RESULTS: Group
      differences between the parents and children were found for the domains of
      Athletic Competence and Physical Appearance. There was either no relationship or
      a low level of association between the child and parent ratings in all five
      domains of self concept assessed. CONCLUSION: Parents were unable to evaluate
      their child's self concept accurately suggesting health professionals should
      gather such information from the child themselves.

PMID- 18720128
TI  - Understanding how to determine the intensity of physical activity--an interview
      study among individuals with rheumatoid arthritis.
AB  - PURPOSE: The study sought to describe variation in understandings of how to
      determine the intensity of physical activity among individuals with rheumatoid
      arthritis (RA). METHOD: Nineteen individuals aged 21-82 years with RA
      participated in semi-structured interviews, which were recorded, transcribed
      verbatim and analysed using a phenomenographic approach. RESULTS: Four
      qualitatively different ways of understanding how to determine the intensity of
      physical activity were identified: a) focus on alterations of bodily features; b)
      focus on will-power and awareness; c) focus on type and performance of activity;
      and d) focus on consequences of the disease. CONCLUSIONS: The results suggest
      that there might be a discrepancy between health professionals and patients with
      RA regarding the understanding of physical activity intensity. This highlights
      the importance for health professionals to recognise what individuals focus most
      attention on when communicating 'intensity'. If necessary, health professionals
      should endeavour to reach a common understanding of evidence-based ways of
      determining physical activity intensity with each patient in order to prescribe
      accurately, and assess, physical activity.

PMID- 18720129
TI  - What is Bobath? A survey of UK stroke physiotherapists' perceptions of the
      content of the Bobath concept to treat postural control and mobility problems
      after stroke.
AB  - OBJECTIVE: The aim of this study was to identify which interventions used to
      treat postural control and mobility are considered part of the Bobath concept
      (BC). DESIGN. Hospital-based UK stroke physiotherapists identified interventions
      which they perceived to be part of the BC from a pre-published list of
      interventions used to treat postural control and mobility problems. Interventions
      that > 75% of participants felt were part of the BC were classified as
      'definitely Bobath'. Interventions that < 25% felt were part of the BC were
      classified as 'definitely not Bobath'. Other interventions were classified as
      'unsure'; those indentified by 50-74% of participants as part of the BC were
      classified as 'probably Bobath' and those indentified 26-49% were classified as
      'probably not Bobath'. RESULTS: Seventy-four physiotherapists from 33 hospitals
      participated. Facilitation, mobilizations and practicing components of activities
      were most strongly associated with the BC. Exercise and the use of equipment were
      identified as 'not' or 'probably not Bobath'. There was uncertainty about
      practicing activities, teaching patients and carers and arranging independent
      practice. CONCLUSIONS: UK stroke physiotherapists perceive that the BC involves
      interventions that focus on facilitating movement, mobilization, practicing
      components of activities and some whole activities. Their views about what is not
      part of the BC and the areas where they are uncertain contrast with British and
      international teachers of the BC. Consequently, it was not possible to define a
      'typical package' of treatment for postural control and mobility that represents
      the BC. Future research into the BC should focus on the effectiveness of
      specific, well-defined interventions.

PMID- 18720130
TI  - Eccentric exercises for the management of tendinopathy of the main body of the
      Achilles tendon with or without an AirHeel Brace. A randomized controlled trial.
      B: Effects of compliance.
AB  - PURPOSE: To evaluate microcirculatory variables in and around the Achilles tendon
      (AT) in patients undergoing a programme of daily eccentric training for the
      management of tendinopathy of the main body of the AT in non-compliant in
      contrast to compliant patients. METHODS: A total of 116 patients with
      tendinopathy of the AT were enrolled for prospective eccentric training. Non
      compliant patients were defined following drop-out due to less than 80%
      participation in the daily eccentric training regimen. RESULTS: Overall 12-week
      compliance was 79% (92/116). The reasons for non-compliance were moving out of
      town (21%, 5/24), overwhelming pain (25%, 6/24), limited discipline (29%, 7/24),
      and surgery (17%, 4/24). Capillary blood flow, tendon and paratendon oxygen
      saturation as well as postcapillary venous filling pressures were not
      significantly different between compliant and non-compliant patients. Gender,
      age, BMI, non steroidal anti inflammatory drugs, corticosteroid medication and
      smoking habits were not significantly different. Only the use of oral
      contraceptives (non- vs. compliant: 54% vs. 10%, p = 0.0001) and walking/swimming
      (46% vs. 70%, p = 0.041) were significantly different. Pain level was reduced
      (5.6 +/- 1.9 to 2.9 +/- 1.2, p < 0.05) following eccentric training. CONCLUSIONS:
      In patients undergoing eccentric training for tendinopathy of the main body of
      the AT, there is no difference in microcirculatory variables regardless of
      compliance with the eccentric exercises programme. With the exception of the more
      frequent use of oral contraceptive medication and less often walking/swimming, no
      predictive factors could be identified in non-compliant patients.

PMID- 18720131
TI  - Postoperative rehabilitation after percutaneous Achilles tendon repair: early
      functional therapy versus cast immobilization.
AB  - PURPOSE: To report a comparative study on postoperative management following
      percutaneous repair of acute Achilles tendon ruptures. METHODS: One hundred and
      three patients with percutaneous repair after acute Achilles tendon rupture were
      prospectively entered in our departmental database. Before July 1999, 15 patients
      were treated postoperatively with below-knee cast immobilization; after July
      1999, patients underwent early functional therapy using a special shoe. Patients
      were seen at 6 weeks, 12 weeks, and 12 months after surgery. Matched pairs were
      selected based upon gender, age, weight, height, body mass index, and the side
      involved. The total number of patients consisted of 14 matched pairs. Compared
      outcomes included clinical evaluation, time away from work, and time before
      return to sports. RESULTS: Fifteen patients had an objective force reduction
      compared to the nonoperated side (9 cast group; 6 shoe group). The mean Achilles
      tendon score was 81 points in the cast group and 88 points in the shoe group.
      Patients in the cast group had a significantly (p = 0.042) longer time before
      return to work (67 days) compared to those in the shoe group (37 days).
      CONCLUSION: Early mobilization in a special shoe is preferable to postoperative
      immobilization after percutaneous Achilles tendon repair. It provides a good
      clinical outcome and shortens the time for return to work and sports.

PMID- 18720132
TI  - Enhancement of gene expression efficiency using cationic liposomes on ovarian
      cancer cells.
AB  - We performed transfection using cationic liposome. According to the gene
      expression level, lined cells were divided into two groups, high and low.
      Introduced gene was monitored with a confocal laser-scanning microscope. The
      percentages of the cells introduced gene reached more than 90% in all line. Then,
      introduced gene was stable in high group, while in low group, it significantly
      decreased. With lysosomotrophic agents, gene expression efficiency was
      significantly reduced.With colchicine, gene expression efficiency did not change
      in high group, but was significantly elevated in low group. A method of liposomal
      transfection could be effective, particularly in low group.

PMID- 18720133
TI  - Polymeric nanoparticles for enhancing antiretroviral drug therapy.
AB  - There is a surge of interest internationally in the study of nanoparticles for
      enhancing antiretroviral (ARV) drug therapy. This paper presents a comprehensive
      review on polymeric nanoparticles for ARV drug therapy. Their main applications
      for targeting to macrophages and the brain, as well as other studies on
      modifications to enhance drug loading, decrease toxicity, and also to increase
      drug absorption are reviewed. The physicochemical characterization properties and
      their in vitro/in vivo performances are summarized. Further studies that need to
      be undertaken for formulation optimization are also identified. This review
      highlights the significant potential that nanoparticles have for the future
      effective treatment of HIV/AIDS patients on ARV drug therapy.

PMID- 18720134
TI  - Transport of surface engineered polyamidoamine (PAMAM) dendrimers across IPEC-J2
      cell monolayers.
AB  - The aim of our study was to prepare arginine-and ornithine-conjugated
      Polyamidoamine (PAMAM) dendrimers and study their permeability across IPEC-J2
      cell monolayers, a new intestinal cell line model for drug absorption studies.
      Arginine and ornithine were conjugated to the amine terminals of the PAMAM(G4)
      dendrimers by Fmoc synthesis. The apical-to-basolateral (AB) and basolateral-to
      apical (BA) apparent permeability coefficients (P(app)) for the PAMAM dendrimers
      increased by conjugating the dendrimers with both of these polyamines. The
      enhancement in permeability was dependent on the dendrimer concentration and
      duration of incubation. Correlation between monolayer permeability and the
      decrease in transepithelial electrical resistance (TEER) with the PAMAM
      dendrimers and the polyamine-conjugated dendrimers suggests that paracellular
      transport is one of the mechanisms of transport across the epithelial cells.
      Cytotoxicity of these surface-modified dendrimers was evaluated in IPEC-J2 cells
      by MTT (methylthiazoletetrazolium) assay. Arginine-conjugated dendrimers were
      insignificantly more toxic than PAMAM dendrimer as well as ornithine-conjugated
      dendrimers. Though investigations on the possible involvement of other transport
      mechanisms are in progress, results of the present study suggest the potential of
      dendrimer-polyamine conjugates as the carriers for antigen/drug delivery through
      the oral mucosa.

PMID- 18720135
TI  - Self-emulsifying drug delivery systems for improving oral absorption of ginkgo
      biloba extracts.
AB  - Self-emulsifying drug delivery systems (SEDDS) are mixtures of oils, surfactants,
      and cosurfactants, which are emulsified in aqueous media under conditions of
      gentle stirring and digestive motility that would be encountered in the
      gastrointestinal tract. We found that SEDDS could efficiently improve oral
      absorption of the sparingly soluble drugs by rapid self-emulsification and
      subsequently dispersion in the absorption sites. Ginkgo biloba extract (GBE) has
      become a widely used herbal remedy for increasing cognitive function in elderly
      people. The main purpose of our work is to prepare SEDDS for improving oral
      absorption of GBE. Pseudoternary phase diagrams were constructed to identify the
      efficient self-emulsification region, and particle size distributions of
      resultant emulsions were determined. The optimized formulation for
      bioavailability assessment consisted of 45% Tween 80-Cremophor EL35 (1:1, w/w),
      10% 1, 2-propanediol, and 45% ethyl oleate. The mean droplet size distribution of
      the optimized SEDDS was approximately 100 nm when diluted with 500-fold volume of
      the distilled water. The in vitro dissolution rates of the active components of
      GBE SEDDS form were significantly faster than those of the GBE tablets. After
      single oral administration of 800 mg GBE as SEDDS or tablets to fasted dogs, the
      relative bioavailability of SEDDS for bilabolide and ginkgolide A and B was
      162.1, 154.6, and 155.8% compared with the reference tablets, respectively. Our
      results suggested the potential and promising use of SEDDS for the efficient
      delivery of the sparingly soluble drugs or traditional Chinese medicines, such as
      GBE by oral administration.

PMID- 18720137
TI  - Preparation and characterization of a submicron lipid emulsion of docetaxel:
      submicron lipid emulsion of docetaxel.
AB  - Docetaxel, a widely used anticancer agent, has sparingly low aqueous solubility,
      thus Tween 80 and ethanol need to be added into its formulation, probably
      resulting in the toxic effects. In this study, we aimed to utilize submicron
      lipid emulsions as a carrier of docetaxel to avoid these potential toxic
      vehicles. Preformulation study was performed for rational emulsions formulation
      design, including drug solubility, distribution between oil and water, and
      degradation kinetics. Supersaturated submicron lipid emulsion of docetaxel was
      prepared by temperature elevation method. Soya oil and Miglyol 812 can
      incorporate docetaxel up to 1.0% (drug to lipid ratio) and were used as the oil
      phase of emulsions. The optimal formulation of docetaxel is composed of 10% oil
      phase, 1.2% soybean lecithin, 0.3% Pluoronic F68, and 0.4 or 0.8 mg/mL docetaxel,
      with particle size in the nanometer range, entrapment efficiency more than 90%,
      and is physicochemically stable at 4 and 25 degrees C for 6 months. Animal
      studies showed that docetaxel emulsion has significantly higher area under the
      curve (AUC) and C(max) in rats compared to its micellar solution. The results
      suggested that the submicron lipid emulsion is a promising intravenous carrier
      for docetaxel in place of its present commercially available docetaxel micellar
      solution with potential toxic effects.

PMID- 18720138
TI  - Strategies to overcome pH-dependent solubility of weakly basic drugs by using
      different types of alginates.
AB  - Weakly basic drugs demonstrate higher solubility at lower pH, thus often leading
      to faster drug release at lower pH. The objective of this study was to achieve pH
      independent release of weakly basic drugs from extended release formulations
      based on the naturally occurring polymer sodium alginate. Three approaches to
      overcome the pH-dependent solubility of the weakly basic model drug verapamil
      hydrochloride were investigated. First, matrix tablets were prepared by direct
      compression of drug substance with different types of sodium alginate only.
      Second, pH-modifiers were added to the drug/alginate matrix systems. Third, press
      coated tablets consisting of an inner pH-modifier tablet core and an outer
      drug/sodium alginate coat were prepared. pH-Independent drug release was achieved
      from matrix tablets consisting of selected alginates and drug substance only.
      Alginates are better soluble at higher pH. Therefore, they are able to compensate
      the poor solubility of weakly basic drugs at higher pH as the matrix of the
      tablets dissolves faster. This approach was successful when using alginates that
      demonstrated fast hydration and erosion at higher pH. The approach failed for
      alginates with less-pronounced erosion at higher pH. The addition of fumaric acid
      to drug/alginate-based matrix systems decreased the microenvironmental pH within
      the tablets thus increasing the solubility of the weakly basic drug at higher pH.
      Therefore, pH-independent drug release was achieved irrespective of the type of
      alginate used. Drug release from press-coated tablets did not provide any further
      advantages as compound release remained pH-dependent.

PMID- 18720139
TI  - Polymers for mucoadhesive drug delivery system: a current status.
AB  - To overcome the relatively short gastrointestinal (GI) time and improve
      localization for oral controlled or sustained release drug delivery systems,
      bioadhesive polymers that adhere to the mucin/epithelial surface are effective
      and lead to significant improvement in oral drug delivery. Improvements are also
      expected for other mucus-covered sites of drug administration. Bioadhesive
      polymers find application in the eye, nose, and vaginal cavity as well as in the
      GI tract, including the buccal cavity and rectum. This article lays emphasis
      mainly on mucoadhesive polymers, their properties, and their applications in
      buccal, ocular, nasal, and vaginal drug delivery systems with its evaluation
      methods.

PMID- 18720140
TI  - CNS disorders--current treatment options and the prospects for advanced
      therapies.
AB  - The development of new pharmaceutical products has successfully addressed a
      multitude of disease states; however, new product development for treating
      disorders of the central nervous system (CNS) has lagged behind other therapeutic
      areas. This is due to several factors including the complexity of the diseases
      and the lack of technologies for delivery through the blood-brain barrier (BBB).
      This article examines the current state of six major CNS disease states:
      depression, epilepsy, multiple sclerosis (MS), neurodegenerative diseases
      (specifically Alzheimer's disease [AD]), neuropathic pain, and schizophrenia.
      Discussion topics include analysis of the biological mechanisms underlying each
      disease, currently approved products, and available animal models for development
      of new therapeutic agents. Analysis of currently approved therapies shows that
      all products depend on the molecular properties of the drug or prodrug to
      penetrate the BBB. Novel technologies, capable of enhancing BBB permeation, are
      also discussed relative to improving CNS therapies for these disease states.

PMID- 18720141
TI  - Clonazepam oral droplets for the treatment of acute epileptic seizures.
AB  - Oral droplet formulations of clonazepam (CZ) were developed to examine their
      potentials as an alternative to i.v. administration for the treatment of acute
      epileptic seizures. Propylene glycol containing 2.5% (wt/wt) CZ with or without
      5.0% (wt/wt) oleic acid (OA) was prepared as a solution by heating at 90 degrees
      C and subsequently lowering the temperature to 30 degrees C. The droplet (20
      microL) was administered to the oral cavity between the lower gum and bottom lip
      before CZ precipitation started. With a droplet of propylene glycol loaded with
      2.5% (wt/wt) CZ and 5.0% (wt/wt) OA, the plasma concentration reached 20 ng/mL
      (minimal effective concentration) within 10 min and was maintained between 20 and
      60 ng/mL, less than a toxic level, for a period of 60 min. For a droplet of
      propylene glycol loaded only with CZ at 2.5% (wt/wt), it took more than 15 min
      for the plasma concentration to reach 20 ng/mL. It is suggested that a droplet of
      CZ/OA/propylene glycol (2.5:5.0:92.5, wt/wt) might be useful as an alternative to
      i.v. injection of CZ for the treatment of acute epileptic seizures.

PMID- 18720142
TI  - Evaluation and optimization of preparative variables for controlled-release
      floatable microspheres prepared by poor solvent addition method.
AB  - The aim of this study was to evaluate and optimize preparative parameters for
      floatable theophylline microspheres prepared by the emulsion-solvent evaporation
      method. A three-factor three-level Box-Behnken design was employed using amount
      of poor solvent, temperature-increase rate and drug loading as independent
      factors, and percentage floating at 3 h and time required for 50% drug release as
      dependent variables. Simultaneous optimization of the parameters for maximum
      buoyancy and desirable drug release was conducted using a partitioned artificial
      neural network. A microsphere using 27.6% of drug loading, 0.29 degrees C/min of
      temperature-increase rate, and 1.7 mL of poor solvent was identified for
      maximizing buoyancy and sustaining drug release.

PMID- 18720143
TI  - Differential scanning calorimetry with curve-fitting program used to
      quantitatively analyze the polymorphic transformation of famotidine in the
      compressed compact.
AB  - Differential scanning calorimetry (DSC) combined with a curve-fitting program was
      utilized to quantitatively determine the polymorphic composition of famotidine in
      the compacts prepared by different compression treatments. Two types of
      famotidine compacts (compact I or II) were prepared by compressing a conical
      shape or a flattened shape of powder bed of famotidine form B. The compact I was
      constructed by a transparent region in the center with an opaque region
      surrounded outside, but the compact II was formed by a whole opaque region only.
      A drilled disc sample was prepared and then directly determined by DSC analysis.
      The Raman spectral results clearly indicate that all the compacts whether in any
      region before DSC determination were only of famotidine form B and independent of
      compression pressure applied. Under DSC determination, however, the curve-fitted
      relative compositions of form B in the drilled disc I sample were gradually
      reduced to 23-24% with the increase of compression pressure, whereas the curve
      fitted relative composition of form A was slowly increased up to 76-77%. A
      transitional phase of famotidine form B (form B*) in the transparent region of
      the compact I after applying >150 kg/cm(2) of compression pressure was easily
      detected, and then transformed to famotidine form A under DSC heating process.
      But this transitional phase and polymorphic transformation of famotidine could
      not be detected by other spectroscopic methods. This suggests that the DSC
      heating system was a preferred method not only to quantitatively analyze the
      polymorphic transformation of famotidine but also to find a newly transitional
      phase of famotidine in the compressed compact.

PMID- 18720144
TI  - Formulation and in vivo evaluation of self-nanoemulsifying granules for oral
      delivery of a combination of ezetimibe and simvastatin.
AB  - Self-nanoemulsifying granules were formulated with the objective of improving the
      bioavailability of the ezetimibe and simvastatin when administered together.
      Composition of self-nanoemulsifying system (SNS) was optimized using various
      modified oils, surfactant, and cosurfactant mixtures. SNSs were mixed with water
      and resultant emulsions were characterized for mean globule size and stability.
      SNSs were adsorbed on hydrophilic colloidal silicon dioxide to give free-flowing
      self-nanoemulsifying granules. Self-nanoemulsifying granules were characterized
      by X-ray diffraction pattern, scanning electron microscopy, dissolution profile,
      and for in vivo performance in hypercholesterolemic rats. X-ray diffraction
      studies and scanning electron microscopy indicated loss of crystallinity and/or
      solubilization of both drugs in the self-nanoemulsifying granules. Self
      nanoemulsifying granules effected substantial increase in dissolution of the
      drugs as compared with pure powder of drugs. In vivo evaluation in rats showed
      significant decrease in the total cholesterol levels and triglyceride levels in
      rats as compared with positive control confirming potential of self
      nanoemulsifying granules as a drug delivery system for the poorly water-soluble
      drugs.

PMID- 18720145
TI  - Acido-basic properties of proton pump inhibitors in aqueous solutions.
AB  - The pharmacological characteristics of proton pump inhibitors are related to
      their protolytic behavior estimated by their pK(a) values. Lansoprazole is a
      potent anti-acid drug from this group. Because of its poor stability a rapid
      spectrophotometric method was developed for the determination of its pK(a)
      values. Three pK(a) values were obtained: an acidic pK(a1) = 8.84 and two basic,
      pK(a2) = 4.15 and pK(a3) = 1.33. These pK(a) values were discussed from the point
      of lansoprazole structure and instability with the aim of locating basic and
      acidic moieties in the molecule of proton pump inhibitors. They were also
      compared with experimentally determined pK(a) values from the literature and with
      some pK(a) values calculated by different programs.

PMID- 18720146
TI  - Ethical observations on the choice of parenteral solvents. Choice of parenteral
      solvent....
AB  - The parenteral administration of insoluble drugs leads to the use of biologically
      active solvents inducing effects associated with ethical cause of concern
      including pain and pharmacological interactions. Selected vehicles currently used
      were ethically and scientifically reviewed. Our investigations allowed
      reinforcing the formulation decision tree with an ethical point of view. The last
      generation of cyclodextrin appears to be the safest solvent. Second choice could
      be lipidic emulsions, third choice being co-solvents, and finally non-ionic
      surfactants because of their hypersensitivity reactions. Screening tests
      including pH, osmolality measurements, cytotoxicity, and hemotoxicity, should
      allow to check the formulation tolerance before the animals' administration.

PMID- 18720147
TI  - Production and in vitro characterization of solid dosage form incorporating drug
      nanoparticles.
AB  - The objective of this study was to develop a tablet formulation of ketoconazole
      incorporating drug nanoparticles to enhance saturation solubility and dissolution
      velocity for enhancing bioavailability and reducing variability in systemic
      exposure. The bioavailability of ketoconazole is dissolution limited following
      oral administration. To enhance bioavailability and overcome variability in
      systemic exposure, a nanoparticle formulation of ketoconazole was developed.
      Ketoconazole nanoparticles were prepared using a media-milling technique. The
      nanosuspension was layered onto water-soluble carriers using a fluid bed
      processor. The nanosuspensions were characterized for particle size before and
      after layering onto water-soluble carriers. The saturation solubility and
      dissolution characteristics were investigated and compared with commercial
      ketoconazole formulation to ascertain the impact of particle size on drug
      dissolution. The drug nanoparticles were evaluated for solid-state transitions
      before and after milling using differential scanning calorimetry (DSC) and powder
      X-ray diffraction (PXRD). This study demonstrated that tablet formulation
      incorporating ketoconazole nanoparticles showed significantly faster rate of drug
      dissolution in a discriminating dissolution medium as compared with commercially
      available tablet formulation. There was no affect on solid-state properties of
      ketoconazole following milling. The manufacturing process used is relatively
      simple and scalable indicating general applicability to enhance dissolution and
      bioavailability of many sparingly soluble compounds.

PMID- 18720148
TI  - Polyelectrolyte-drug complexes of lambda carrageenan and basic drugs: relevance
      of particle size and moisture content on compaction and drug release behavior.
AB  - The interaction between polyelectrolytes (PE) and oppositely charged drugs (D)
      results in complexes (PE-D) that can be exploited in controlled release drug
      delivery systems. The aim of this work is to better understand the relevance of
      some preparative parameters such as moisture content and particle size on the
      performance of two PE-D complexes to be used in oral controlled release tablets.
      PE-D complexes containing diltiazem HCL (DTZ) or metoprolol tartrate (MTP) and
      lambda carrageenan were obtained at two particle size levels (<45 microm and 75
      105 microm), maintained at different values of relative humidity (RH) (11, 52,
      75, and 93%), and compressed. The tablets were characterized for porosity,
      hardness, moisture content, and contact angle. Drug release profiles were fitted
      to the Weibull equation, and a factorial design was used to understand the
      relevance of particle size and RH% on release rate as a function of medium pH.
      The results indicated that the hydrophobic character of the complex between PE
      and D depended on the drug and in the present case was more pronounced for DTZ
      than for MTP. This in turn affected the possible release mechanism and therefore
      the importance of particle size and RH%.

PMID- 18720149
TI  - Dry coating of soft gelatin capsules with HPMCAS.
AB  - Dry coating is an innovative powder-layering technique that enables the formation
      of coatings on solid dosage forms with no need for using water or organic
      solvents. This technique envisages the distribution of polymer powder blends onto
      substrate cores and the concurrent or alternate nebulization of liquid
      plasticizers. In this work, a dry coating process based on hydroxypropyl
      methylcellulose acetate succinate (HPMCAS) was set up in a rotary fluid bed
      equipment to prepare enteric-coated soft gelatin capsules. Promising results were
      obtained in terms of process feasibility and product characteristics, thus
      suggesting the possibility of advantageous applications for the investigated
      technique when dealing with gelatin capsule substrates.

PMID- 18720150
TI  - Carboxymethyl mungbean starch as a new pharmaceutical gelling agent for topical
      preparation.
AB  - An application of carboxymethyl mungbean starch (CMMS) as a gelling agent in the
      topical pharmaceutical preparation was investigated. CMMS was prepared using
      specific conditions that yielded a high-viscosity product. Polymer gels and gel
      bases were prepared at 1-10% (wt/wt), and physicochemical studies were carried
      out in comparison with four standard gelling agents: carbopol 940 (CP),
      hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC), and sodium
      carboxymethyl cellulose (SCMC). Piroxicam was used as a model drug to study the
      drug release profile of the gel formulations. The tackless, greaseless, and
      transparent CMMS gels exhibited pseudoplastic behavior with thixotropy at
      concentrations less than 5% (wt/wt). At a concentration of 5% (wt/wt) and higher,
      the semisolid gels showed plastic flow characteristics. Viscosity and X-ray
      diffraction results indicated a good compatibility between CMMS and the acidic
      piroxicam. No precipitation of piroxicam or phase separation was observed during
      a stability test. The release rate of piroxicam from 3% (wt/wt) CMMS gel was
      1,003.79 +/- 105.08 microg/cm(2), which was comparable with 947.66 +/- 133.70
      microg/cm(2) obtained from a 0.5% (wt/wt) carbopol formulation. The release
      profiles of both formulations were consistent and remained unchanged after 2
      months' storage. Viscosity played an important role in controlling the release
      rate of low concentration CMMS formulations by regulating the drug diffusion. At
      a concentration of 5% (wt/wt) CMMS and higher, the release rates of piroxicam
      were not significantly different. A plausible explanation based on the nature of
      the gelling agent was proposed. Stability and drug release profiles of CMMS and
      commercial gelling agents were compared. The results supported the potential use
      of CMMS as a new, effective gelling agent for topical gel preparation.

PMID- 18720151
TI  - Experiences of whanau/families when injured children are admitted to hospital: a
      multi-ethnic qualitative study from Aotearoa/New Zealand.
AB  - OBJECTIVES: Several quantitative studies in the international literature have
      described disparities in the provision of and access to health services for a
      variety of health conditions among 'minority' populations. This New Zealand
      qualitative study aimed to explore and describe the experiences of indigenous
      Maori and Pacific families (both minority populations) and Pakeha (New Zealand
      European) families when their children were admitted to hospital for an
      unintended injury. DESIGN: Twenty-three children (eight Maori, eight Pacific and
      seven Pakeha) who were admitted to hospital following an injury were selected
      using maximum variation sampling from a trauma database and snowball sampling. In
      depth individual and group interviews undertaken with the child's whanau/family
      explored the issues they encountered in the hospital setting. The data were
      analysed by key ideas and coded into main themes. Each strand was analysed
      separately by lead researchers of the same ethnic group prior to a comparative
      synthesis of the overall findings. RESULTS: While many families praised the
      dedication of the staff, the interviews revealed important concerns regarding
      their encounters with hospitals and related health and support services. These
      could be broadly characterised as (a) inadequate communication and information;
      (b) difficulties negotiating an environment perceived as foreign; (c) the stress
      of conflicting demands placed on families; and (d) issues relating to ethnicity
      and cultural miscommunication. Of note, many Maori and Pacific whanau/families
      felt particularly alienated within the hospital setting and did not appear to see
      themselves as being entitled to high-quality information or services. CONCLUSION:
      The findings have important implications for the structure, professional and
      institutional practices in the delivery of health services. The research also
      indicates the need for wider societal policies that increase Maori and Pacific
      whanau/families' sense of entitlement to the full range of available support
      services, and reduce alienation within public institutions such as hospitals.

PMID- 18720162
TI  - Bone morphogenetic protein-2 stimulates chondrogenic expression in human nasal
      chondrocytes expanded in vitro.
AB  - Articular cartilage contains an extracellular matrix with characteristic
      macromolecules such as type II collagen. Because this tissue is avascular and
      mature chondrocytes do not proliferate, cartilage lesions have a limited capacity
      for healing after trauma. Autologous chondrocyte implantation (ACI) is widely
      used for the treatment of patients with focal damage to articular cartilage.
      However, this method faces a major issue: dedifferentiation of chondrocytes
      occurs during the long-term culture necessary for mass cell production. The aim
      of this study was to determine if the step of cell amplification required for ACI
      could benefit from the use of bone morphogenetic protein (BMP)-2, a potent
      regulator of chondrogenic expression. Chondrocytes were isolated from human nasal
      cartilage, a hyaline cartilage like articular cartilage and were serially
      cultured in monolayers. After one, two or three passages, BMP-2 was used to
      evaluate the chondrogenic potential of the dedifferentiated chondrocytes, at the
      gene and protein level. We found that BMP-2 can reactivate the program of
      chondrogenic expression in dedifferentiated chondrocytes. To gain insight into
      the molecular mechanisms involved in the responsiveness of chondrocytes to BMP-2,
      we examined the phosphorylation of Smad proteins and the interaction of the Sry
      type high-mobility-group box (Sox) transcription factors with the cartilage
      specific enhancer of the type II procollagen gene. Our results show that BMP-2
      acts by stimulating Smad phosphorylation and by enhancing DNA-binding of the Sox
      transcription factors to the specific enhancer of the type II procollagen gene.
      Thus, this study reveals the potential use of BMP-2 as a stimulatory agent in
      conventional ACI strategies.

PMID- 18720163
TI  - Evaluation of serum biomarkers in nutritional disorders: glycated apolipoprotein
      B, fasting serum glucose, fructosamine, stable and labile glycated hemoglobin in
      diabetic and non-diabetic subjects.
AB  - Glycated apolipoprotein B (ApoB-G), a non enzymatically glycated protein, has
      recently been associated with myocardial infarction. Our aim is to evaluate, in
      diabetic and non diabetic subjects, the relationship of ApoB-G with serum fasting
      glucose, fructosamine, stable and labile fractions of glycated hemoglobin
      ((S)HbA(1c), (L)HbA(1c), respectively) and insulin. The subjects were recruited
      from a previous study on ApoB-G and myocardial infarction: 141 of them were
      studied, 43 with and 98 without diabetes. ApoB-G was measured using a monoclonal
      antibody, and linear regression and correlation were used for statistical
      analysis of the data. ApoB-G was higher in diabetic than in non diabetic
      subjects. There was a statistically significant correlation of ApoB-G with
      triglycerides (r = 0.38, p = 0.01) in diabetic subjects, and with total proteins
      (r = 0.37, p = 0.0002), triglycerides (r = 0.34, p = 0.0007), and cholesterol (r
      = 0.23, p = 0.02) in non diabetic subjects. In the most parsimonious multiple
      linear regression model of ApoB-G on all the other serum variables, there was a
      statistically significant association of ApoB-G with triglycerides, in both
      diabetic and non diabetic subjects. The main results of this study suggest that
      serum ApoB-G is associated with serum triglycerides in both diabetic and non
      diabetic subjects.

PMID- 18720164
TI  - Serum 90K/Mac-2 binding protein (Mac-2BP) as a response predictor to
      peginterferon and ribavirin combined treatment in HCV chronic patients.
AB  - 90K/Mac-2BP glycoprotein is involved in the immune defense against a variety of
      neoplasms and viral infections, modulating the activity of several effectors such
      as natural killer cells. Quite interestingly, 90K/Mac-2BP is associated to a poor
      response to interferon (IFN) alpha in hepatitis C virus (HCV) infected patients.
      Here, in 70 consecutive HCV chronic patients, we have evaluated 90K basal levels
      as a response predictor to combined therapy with Peginterferon and Ribavirin. We
      have found higher 90K levels in genotype 1/4 than in genotype 2/3 (p = 0.006) and
      in 62.5% of non-responders than in 20% of responders (p < 0.001). Genotype 1/4,
      higher 90K and gamma glutamyl transferase (gammaGT) levels resulted independently
      associated to a status of refractoriness to therapy. Consequently, evaluation of
      90K serum levels seems to be a promising useful marker of response to combined
      therapy in HCV disease.

PMID- 18720165
TI  - f-Met-Leu-Phe stimulates nitric oxide production in chick embryo neurons: the
      role of NF-kB.
AB  - N-formyl-methionyl-leucyl-phenylalanine (fMLP) is a major chemotactic factor
      produced by Escherichia coli and other Gram-negative bacteria. In avian models
      the fMLP effects and the possible expression of FPRs have been poorly
      investigated. This report demonstrates that fMLP stimulation in vitro is able to
      elicit significant cellular responses from 10-day chick embryo nerve cells. Cell
      treatment with 10(-7) M fMLP at 37 degrees C induces a dramatic increase of
      nitric oxide (NO) production, after 24, 48, and 72 h, respectively. After 72 h of
      treatment with 10(-7) M fMLP the maximum nuclear translocation of the NF-kB
      complex protein p65 is visible, corresponding to the greatest NO production. In
      this context, 72 h of fMLP stimulation lead to a marked expression of the
      antiapoptotic protein Bcl-2, involved in cell survival. This suggests that
      activation of the NF-kB complex plays a protective role in chick neuronal cells
      treated with fMLP, confirmed by the significant neuronal cells degeneration
      observed after NF-kB inhibition with the specific inhibitor, TPCK. Overall, these
      data suggest a possible protective mechanism displayed by neurons against toxic
      molecules, like NO, released after cell exposure to bacterial products.

PMID- 18720166
TI  - Suppressive effects of the flavonoids quercetin and luteolin on the accumulation
      of lipid rafts after signal transduction via receptors.
AB  - Quercetin (QUER) and luteolin (LUTE) are dietary flavonoids capable of regulating
      the production of cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and
      interleukin-6 (IL-6). However, their mechanisms of action are not fully
      understood. In lipopolysaccharide-triggered (LPS)-triggered signaling via Toll
      like receptor 4 (TLR4), QUER and LUTE suppresses not only the degradation of the
      inhibitor of kappaB (IkappaB), with resultant activation of nuclear factor-kappaB
      (NF-kappaB), but also the phosphorylation of p38 and Akt in bone marrow-derived
      macrophages that have been stimulated with LPS. We report here that, in TNF-alpha
      induced signaling, QUER and LUTE significantly suppressed the production of IL-6
      and activation of NF-kappaB. Accumulation of lipid rafts, the initial step in the
      signaling pathway, was significantly inhibited when macrophages were treated with
      QUER or with LUTE prior to exposure to LPS. Similarly, the accumulation of lipid
      rafts was inhibited by the flavonoids when B cells were activated via the
      membrane IgM and when T cells were activated via CD3. In contrast, QUER and LUTE
      did not inhibit the activation of phorbol myristate acetate-induced NF-kappaB in
      macrophages. Our observations suggest that QUER and LUTE interact with receptors
      on the cell surface and suppress the accumulation of lipid rafts that occurs
      downstream of the activation of the receptors.

PMID- 18720167
TI  - Amelioration of skewed Th1/Th2 balance in tumor-bearing and asthma-induced mice
      by oral administration of Agaricus blazei extracts.
AB  - We showed in a previous study that hot-water extracts of Agaricus blazei
      (Agaricus extracts) had anti-tumor activity to Meth A fibrosarcoma, but it
      remains unclear whether the Agaricus extracts ameliorate the skewed balance of
      type-1 T helper (Th1) and type-2 T helper (Th2) cells. We examined whether
      Agaricus extracts effect the skewed Th1/Th2 balance in tumor-bearing and asthma
      induced mice. When Meth A-bearing mice were given orally either Agaricus extracts
      or water once a day starting 5 days after tumor implantation, spleen T cells,
      prepared from tumor-bearing mice treated with Agaricus extracts, in response to
      anti-CD3 monoclonal antibody produced significantly higher levels of interferon
      gamma (IFN-gamma) than that of controls. The mRNA expression of IFN-gamma
      inducing protein 10 and the frequency of CD69(+) or CD49d(+) cells, among
      activated T cells infiltrated into tumors, significantly increased in Agaricus
      treated mice, compared with those of tumor-controls. In asthma-induced mice,
      treatment with the Agaricus extracts caused significant downregulation of OVA
      specific antibody responses of IgG1 and IgE but not of IgG2a, and significantly
      decreased total cell numbers, levels of interleukin 5, and eosinophil numbers in
      bronchial alveolar lavage fluids. IFN-gamma production by anti-CD3-stimulated
      spleen cells, obtained from Agaricus-treated mice, significantly increased. Our
      results strongly suggest that oral administration of Agaricus extracts
      ameliorates the Th1/Th2 balance from the Th2-skewed conditions.

PMID- 18720168
TI  - Effect of restraint stress duration on humoral immune response in albino rats:
      modulation by chlordiazepoxide.
AB  - We evaluated the effect of restraint stress (1 hr/day) for 6, 10, 14 and 21 days
      on antibody response against sheep RBC (SRBC) and modulation by chlordiazepoxide
      (CDP) pretreatment (10 mg/kg/day) in albino rats. Anti-SRBC titer was
      significantly decreased with increase in number of days of restraint stress
      exposure. CDP pretreatment significantly reversed the effects of 6, 10 and 14
      (but not of 21) days of restraint stress. CDP treatment for 21 days per se
      suppressed immune response, but no additive effect was observed. CDP was not
      effective in chronic stress (i.e., 21 days of stress). Hence, the rationale
      behind benzodiazepines therapy in chronic stress needs to be evaluated.

PMID- 18720169
TI  - Assessment of intra-urban variability in outdoor air quality and its health
      risks.
AB  - Ambient air quality along with micrometeorological data was measured in a
      suburban area of India, from March 2006 to February 2007 in order to assess the
      intra-urban variability of air pollutants in different parts of the city. The
      prevalences of asthma and respiratory disorders were determined using a
      questionnaire survey of 750 adults. The association between intra-urban
      variability of air pollution and respiratory diseases were evaluated with
      logistic regression analyses. Compared with subjects staying 5.0 km away from a
      main road to those subjects living within 0.5 km and 1.0 km had odds ratios of
      1.00 (95% CI, 0.85 to 1.50), 3.57 (95% CI, 3.00 to 3.95), and 3.00 (95% CI, 2.85
      to 3.50), respectively for doctor-diagnosed asthma. A reduction of measured
      pollutant concentration with increase in distance from the main road was
      observed. The study demonstrated that residential exposure to highly trafficked
      roads is associated with respiratory diseases. Considering the continuing rise in
      motorized vehicle use and the paramount role of inhalation toxicology, these
      findings have high public health relevance and should be corroborated in
      prospective studies.

PMID- 18720170
TI  - Lung deposition of droplet aerosols in monkeys.
AB  - Nonhuman primates are often the animal models of choice to study the infectivity
      and therapy of inhaled infectious agents. Most animal models for inhaled
      infectious diseases use aerosol/droplets generated by an atomization technique
      such as a Collison nebulizer that produces particles in the size range of 1 to 3
      microm in diameter. There are few data in the literature on deposition patterns
      in monkeys. Our study was designed to measure the deposition pattern in monkeys
      using droplets having diameters of 2 and 5 microm using an exposure system
      designed to expose monkeys to aerosols of infectious agents. Six cynomolgus
      monkeys were exposed to droplets. The aerosol solution was generated from a Vero
      cell supernate containing DMEM + 10% fetal bovine serum tagged with Tc-99m
      radiolabel. Collison and Retec nebulizers were used to generate small and large
      droplets, respectively. The particle size (as determined from a cascade impactor)
      showed an activity median aerodynamic diameter (AMAD) of 2.3 and 5.1 microm for
      the Collison and Retec nebulizer, respectively. The animals were anesthetized,
      placed in a plethysmography box, and exposed to the aerosol. The deposition
      pattern was determined using a gamma camera. Deposition in the head airways was
      39% and 58% for 2.3- and 5.1-microm particle aerosols, respectively, whereas the
      deposition in the deep lung was 12% and 8%, respectively. This information will
      be useful in developing animal models for inhaled infectious agents.

PMID- 18720171
TI  - Antioxidant potential of commercially available cumin (Cuminum cyminuml inn) in
      Pakistan.
AB  - Owing to increased safety concerns about synthetic antioxidants, exploitation of
      safer antioxidants based on natural origin is the focus of research nowadays.
      Cumin is a common spice and is used as a routine supportive cooking agent.
      Extracts of cumin were prepared in methanol, ethanol, dichloromethane and hexane
      by employing Soxhlet extraction apparatus. Determination of the total phenolic
      content, chelating activity, reducing power and free radical scavenging activity
      were taken as parameters for the assessment of antioxidant properties. The
      findings of this study suggest cumin to be a potent source of antioxidants.
      Results from the different parameters were in agreement with one another.

PMID- 18720172
TI  - Psychological disorder, symptom severity and weight loss in inpatient adolescent
      obesity treatment.
AB  - OBJECTIVE: This study aimed to investigate whether psychological disorders and
      symptom severity hamper weight loss in obese adolescents and explored the effect
      of evidence-based adolescent obesity treatment on psychological disorders and
      symptom severity. METHOD: Participants were 66 adolescents admitted for a 10
      month obesity treatment programme. At the start of treatment both clinical
      interviews and self-report questionnaires were administered. Weight loss was
      registered at several time points. Half of the sample was invited to complete
      questionnaires and be interviewed once again at the end of the programme.
      RESULTS: Baseline degree of overweight was the strongest predictor of weight
      loss. The presence of at least one psychological disorder appeared a negative
      predictor of weight loss after four months. At post-test, a decrease in eating,
      shape and weight concern and binge eating episodes was demonstrated. A similar
      trend was found for internalizing symptoms. All eating disorders resolved, but a
      substantial number of adolescents still suffered from psychological disorders at
      the end of treatment. CONCLUSION: During inpatient obesity treatment, youngsters
      who are more severely obese lose most weight. In girls and in adolescents
      suffering from psychological disorders, long-term care should be the aim to
      prevent an experience of failure. From a psychological health perspective, the
      inclusion of psychotherapy during inpatient obesity treatment for adolescents
      suffering from psychiatric disorders is worth considering. All together, the
      findings of this study demonstrate the importance of adopting both a medical and
      a psychological perspective on obesity (treatment) in youth.

PMID- 18720173
TI  - A comparison of indirect versus direct measures for assessing physical activity
      in the pediatric population: a systematic review.
AB  - BACKGROUND: Accurate assessment of physical activity (PA) in children and
      adolescents is required to establish PA levels, monitor changes and inform public
      healthy policy. This study systematically reviews the literature to determine the
      extent of agreement between indirect (e.g., questionnaire) and direct (e.g.,
      accelerometry) assessments of PA in pediatric populations (<or=19 years).
      METHODS: Literature was identified through searching electronic databases (e.g.,
      MEDLINE, EMBASE), websites of relevant organizations and conference abstracts
      until April 2007. Studies were included if they collected indirect and direct
      measures of PA in pediatric populations and were reported in English. Quality of
      included studies was appraised using a modified Downs and Black tool. RESULTS: A
      total of 83 studies were included; 24 describing comparable data and 59 including
      a correlation analysis. The majority of correlations reported between indirect
      and direct measures were low-to-moderate (range: -0.56 to 0.89). Overall, 72% of
      the indirect measures overestimated the directly measured values. Combined
      gender, as well as male- and female-only data comparing indirect measures to
      accelerometery, heart rate monitoring or direct observation, all reported an
      overestimation by indirect method. A similar trend was observed in combined
      gender data comparing indirect measures with doubly labelled water; however, the
      opposite trend was observed in the male- and female-only data with a slight
      underestimation by indirect measure. CONCLUSIONS: Substantial discrepancies and
      moderate correlations between indirect methods and direct measures of assessing
      PA in pediatric populations are of concern, especially when trying to establish
      relationships with health outcomes.

PMID- 18720174
TI  - The feasibility of ambulatory screen time in children.
AB  - PURPOSE: A walking media station was developed, which enables normally seated
      screen activities to be conducted whilst walking. This study tests feasibility of
      the walking media station and provides preliminary evidence of the acceptability
      of the device in the home environment. METHODS: Twenty-nine healthy children
      (mean age 9.6 years) participated in the testing of the newly developed walking
      media station in the laboratory and in the home environment. RESULTS: Steady gait
      walking at 1 km.hr(-1) was achieved by all the children in less than 1 minute.
      There was no significant difference between computer game score during seated and
      walking play modes and no increase in energy cost when computer game play was
      added to walking (p>0.05). When given the choice in the home, all chose to use
      the walking media station rather than play seated. When asked: "If this unit were
      yours to keep forever, would you play video games on it?" all responded
      affirmatively. CONCLUSION: These data demonstrate that when given a walking media
      station, children can and will use it. Re-engineering regular walking into
      otherwise seated gaming minimizes disruption to normal routines and provides an
      innovative and creative opportunity for further investigation into the
      sustainability and clinical outcomes of reducing sitting time and increasing
      physical activity.

PMID- 18720175
TI  - Evaluation of a 6-month multi-disciplinary healthy weight management program
      targeting urban, overweight adolescents: effects on physical fitness, physical
      activity, and blood lipid profiles.
AB  - This study evaluated preliminary physical fitness, physical activity, and blood
      lipid profile data obtained from overweight adolescents upon enrolling in a
      healthy weight management program and following 6 months of program
      participation. One hundred and sixty-eight participants (13.4+/-1.8 years, 37.9+/
      8.3 kg/m(2), 59.5% female and 76.2% African-American) enrolled in the program.
      The intervention addressed factors related to nutrition, physical activity, and
      other behaviors related to weight management. Sixty-four participants (38.1%)
      completed 6 months of program participation. While there was no significant
      reduction in body mass or body mass index (BMI), BMI z-score was reduced by 1.2%
      (p < 0.05), cardiorespiratory fitness was increased by 10.8% (p = 0.001), body
      fat percentage was reduced by 2.6% (p = 0.001), total cholesterol was reduced by
      7.2% (p < 0.001), and low density lipoprotein (LDL-C) was reduced by 8.4% (p <
      0.001) at 6 months. Continued development and evaluation of programs designed to
      prevent and treat child and adolescent overweight is warranted to address this
      major public health issue.

PMID- 18720176
TI  - A cross-language study of verbal and visuospatial working memory span.
AB  - This cross-language study of working memory compared 30 English speakers and 30
      Mandarin Chinese speakers on backward and forward digit and spatial span.
      Mandarin speakers had greater spans on forward digit and spatial span than did
      English speakers. Effects were most significant for digit span where the mean
      score of the English speakers was equivalent to the lowest individual score from
      Mandarin speakers. Shorter articulation time for digits in spoken Mandarin may
      account for higher digit spans than those observed in English. The current study
      indicates that clinical applications of working memory tests should consider
      cross-language effects, particularly in the evaluation of verbal working memory
      deficits.

PMID- 18720177
TI  - Explicit identification and implicit recognition of facial emotions: I. Age
      effects in males and females across 10 decades.
AB  - A number of psychiatric and neurological disorders are characterized by
      impairments in facial emotion recognition. Recognition of individual emotions has
      implicated limbic, basal ganglionic, and frontal brain regions. Since these
      regions are also implicated in age-related decline and sex differences in emotion
      processing, an understanding of normative variation is important for assessing
      deficits in clinical groups. An internet-based test ("WebNeuro") was administered
      to 1,000 healthy participants (6 to 91 years, 53% female) to assess explicit
      identification of basic expressions of emotion (happiness, sadness, fear, anger,
      disgust, neutral). A subsequent implicit recognition condition was based on a
      priming protocol, in which explicit identification provided the "study" phase.
      Responses were most accurate for happiness and slowest for fear in the explicit
      condition, but least accurate for happiness and fastest for fear in the implicit
      condition. The effects of age, by contrast, showed a similar pattern for both
      explicit and implicit conditions, following a nonlinear distribution in which
      performance improved from childhood through adolescence and early adulthood and
      declined in later adulthood. Females were better than males at explicit
      identification of fear in particular. These findings are consistent with the
      priority of threat-related signals, but indicate opposing biases depending on
      whether emotion processing is conscious or nonconscious. The lifespan trends in
      emotion processing over 10 decades point to an interaction of brain-based
      (maturation, stability, and then atrophy of cortical and subcortical systems) and
      experiential contributing factors. These findings provide a robust normative
      platform for assessing clinical groups.

PMID- 18720179
TI  - Neuropsychological impairment and psychosis in mania.
AB  - Deficits involving executive function, working memory, speed of information
      processing, and new learning occur in many people with mania. Factors that
      predict impairment remain poorly understood, but there are indications that
      psychotic features may correspond with increased risk of neurocognitive
      dysfunction during manic episodes. The current study examined neuropsychological
      function in 40 inpatients with bipolar I mania, 24 of whom presented with
      psychotic features. Compared to a control group, the inpatients showed worse
      executive function, speed of information processing, new learning, and dexterity.
      Nonetheless, presence of psychotic features failed to distinguish the inpatients
      with mania. Thus, psychotic features do not appear to increase neurobehavioral
      morbidity in people with mania, but presence of mania clearly corresponded with
      neurobehavioral dysfunction. Implications of these data for clinical practice and
      our understanding of bipolar disorder are discussed.

PMID- 18720178
TI  - Explicit identification and implicit recognition of facial emotions: II. Core
      domains and relationships with general cognition.
AB  - Both general and social cognition are important in providing endophenotypic
      markers and predicting real-world functional outcomes of clinical psychiatric
      disorders. However, to date, focus has been on general cognition, rather than on
      core domains of social/emotional cognition. This study sought to determine core
      domains of emotion processing for both explicit identification and implicit
      recognition and their relationships with core domains of general cognition. Age
      effects and sex differences were also investigated. A sample of 1,000 healthy
      individuals (6 to 91 years, 53.5% female) undertook the WebNeuro tests of emotion
      identification and recognition and tests of general cognitive function. Factor
      analysis revealed seven core domains of emotion processing: speed of explicit
      emotion identification, speed of implicit emotion recognition, implicit emotion
      recognition accuracy, "threat" processing, sadness-disgust identification,
      "positive emotion" processing, and general "face perception." Seven corresponding
      core domains of general cognition were identified: information-processing speed,
      executive function, sustained attention/vigilance, verbal memory, working-memory
      capacity, inhibition/impulsivity, and sensorimotor function. Factors of emotion
      processing generally showed positive associations with those of general cognitive
      function, suggesting commonality in processing speed in particular. Moreover, age
      had a consistent nonlinear impact on both emotion processing and general
      cognitive factors, while sex differences were more specific. These findings
      contribute to a normative and standardized structure for assessment of emotional
      and general cognition in clinical groups.

PMID- 18720180
TI  - An examination of decision making in bulimia nervosa.
AB  - BACKGROUND: Patients with eating disorders favor immediate gratification and
      ignore long-term negative consequences. This study investigated decision making
      in bulimia nervosa using the Iowa Gambling Task (IGT) and skin conductance
      responses (SCR). METHOD: A total of 26 bulimia nervosa patients and 51 healthy
      controls took part in this study; 29 patients with anorexia nervosa were included
      for comparison. RESULTS: Bulimia nervosa patients performed poorly in the IGT,
      but showed no decrease in anticipatory SCR, whereas a markedly diminished
      anticipatory SCR was seen in the anorexia nervosa group. CONCLUSIONS: This
      finding does not support the somatic marker hypothesis. Impaired decision making
      was associated with obsessive-compulsive traits.

PMID- 18720181
TI  - Neurocognitive performances in participants of at-risk mental state for
      schizophrenia and in first-episode patients.
AB  - As suggested by the neurodevelopmental model, neurocognitive disturbances are
      core features of schizophrenia spectrum disorders. The aim of the present study
      was to explore the neurocognitive performance of symptomatically defined high
      risk participants as well as first-episode patients on tests of verbal memory,
      executive functioning, working memory, and attention. The sample consisted of 54
      participants at risk for schizophrenia and 37 patients with a first episode of
      psychosis. The high-risk group exhibited a similar cognitive performance profile
      to that of the first-episode participants when compared with normative data. The
      neurocognitive functioning of both patient groups were within standard average
      range at most of the cognitive domains. Moreover the intellectual functioning of
      both groups was within higher average level, while decreased "hit rates" could be
      observed within both subtests "Figures" and "Symbols" of the Continuous
      Performance Test-Identical Pairs Version (CPT-IP) in the group of first-episode
      patients. Direct comparison between the clinical groups did show increasing
      impairments of these parameters in first-episode patients compared to high-risk
      participants. Results suggest that high-risk participants do perform at average
      neurocognitive performance levels at all tested domains compared with normative
      data. Compared to norm values first-episode patients showed decreased attention
      abilities.

PMID- 18720183
TI  - Intraindividual variability across cognitive domains: investigation of dispersion
      levels and performance profiles in older adults.
AB  - A growing body of research suggests that substantial variability exists among
      cognitive abilities within individuals. This within-person variability across
      cognitive domains is termed dispersion. The present study investigated the
      relationship between aging and dispersion of cognitive functions both
      quantitatively (overall levels of dispersion) and qualitatively (patterns of
      dispersion) in a sample of 304 nondemented, older adults aged 64 to 92 years (M =
      74.02). Quantitatively, higher levels of dispersion were observed in the old-old
      adults (aged 75-92 years) and those identified as having experienced cognitive
      decline, suggesting that dispersion level may serve as a marker of cognitive
      integrity. Qualitatively, three distinct dispersion profiles were identified
      through clustering methods, and these were found to be related to demographic,
      health, and performance characteristics of the individuals, suggesting that
      patterns of dispersion may be meaningful indicators of individual differences.

PMID- 18720182
TI  - Abbreviated neuropsychological assessment in schizophrenia: prediction of
      different aspects of outcome.
AB  - The aim of this study was to identify the best subset of neuropsychological tests
      for prediction of several different aspects of functioning in a large (n = 236)
      sample of older people with schizophrenia. While the validity of abbreviated
      assessment methods has been examined before, there has never been a comparative
      study of the prediction of different elements of cognitive impairment, real-world
      outcomes, and performance-based measures of functional capacity. Scores on 10
      different tests from a neuropsychological assessment battery were used to predict
      global neuropsychological (NP) performance (indexed with averaged scores or
      calculated general deficit scores), performance-based indices of everyday-living
      skills and social competence, and case-manager ratings of real-world functioning.
      Forward entry stepwise regression analyses were used to identify the best
      predictors for each of the outcomes measures. Then, the analyses were adjusted
      for estimated premorbid IQ, which reduced the magnitude, but not the structure,
      of the correlations. Substantial amounts (over 70%) of the variance in overall NP
      performance were accounted for by a limited number of NP tests. Considerable
      variance in measures of functional capacity was also accounted for by a limited
      number of tests. Different tests constituted the best predictor set for each
      outcome measure. A substantial proportion of the variance in several different NP
      and functional outcomes can be accounted for by a small number of NP tests that
      can be completed in a few minutes, although there is considerable unexplained
      variance. However, the abbreviated assessments that best predict different
      outcomes vary across outcomes. Future studies should determine whether responses
      to pharmacological and remediation treatments can be captured with brief
      assessments as well.

PMID- 18720184
TI  - A functional application of the spacing effect to improve learning and memory in
      persons with multiple sclerosis.
AB  - The present study examined the utility of using spaced learning trials (when
      trials are distributed over time) versus massed learning trials (consecutive
      learning trials) in the acquisition of everyday functional tasks. In a within
      subjects design, 20 participants with multiple sclerosis (MS) and 18 healthy
      controls (HC) completed two route learning tasks and two paragraph reading tasks.
      One task in each area was presented in the "spaced" condition, in which the task
      was presented to the participants three times with 5-minutes break between each
      trial, and the second task in each area was presented in the "massed" condition,
      in which the task was presented three consecutive times to the participants. The
      dependent variables consisted of recall and recognition of the paragraphs and
      routes both immediately and 30 minutes following initial learning. Results showed
      that for paragraph learning, the spaced condition significantly enhanced memory
      performance for this task relative to the massed condition. However, this effect
      was not demonstrated in the route learning task. Thus, the spacing effect can be
      beneficial to enhance recall and performance of activities of daily living for
      individuals with MS; however, this effect was significant for verbal tasks
      stimuli, but not for visual tasks stimuli. It will be important during future
      investigations to better characterize the factors that maximize the spacing
      effect.

PMID- 18720185
TI  - Topical antioxidant application enhances the effects of facial microdermabrasion.
AB  - BACKGROUND: Microdermabrasion has been accepted as a reliable, non-invasive
      method for facial rejuvenation. Recently, there has been interest in combining
      this technique with other modalities to increase its efficacy. The purpose of
      this study was to determine whether the addition of an antioxidant-based serum
      enhanced the dermatologic changes seen following microdermabrasion. METHODS: Ten
      female volunteers, aged 38-52 years, underwent a series of six diamond tip
      crystal-free microdermabrasion facial treatments spaced 7-10 days apart. An
      antioxidant serum rich in polyphenols was pneumatically applied to half the face
      immediately after each microdermabrasion treatment. Skin biopsies and skin
      polyphenolic antioxidant levels, determined by Raman spectroscopy, were obtained
      prior to and after the study period. Investigator ratings for efficacy were
      analyzed after the study period and compared to baseline. RESULTS: Compared with
      the skin treated with microdermabrasion only, the skin treated with
      microdermabrasion plus antioxidant demonstrated significantly increased epidermal
      and papillary dermal thickness, and increased fibroblast density (p < 0.01).
      There was increased hyalinization of the papillary dermis with newly deposited
      collagen fibers. Skin polyphenolic antioxidant levels increased 32% in the skin
      treated with the polyphenolic antioxidant serum after microdermabrasion (p <
      0.01). Clinical efficacy variables were significantly more improved in the
      antioxidant group when compared to baseline (p < 0.01). These changes were
      supported clinically via digital photography. CONCLUSION: The addition of a
      polyphenolic antioxidant serum to a facial microdermabrasion regimen enhanced the
      clinical and histological changes seen following microdermabrasion alone. This
      combination should strengthen the use of microdermabrasion as a non-invasive
      facial rejuvenation tool and support the role of topical antioxidants as anti
      aging factors.

PMID- 18720186
TI  - Validation of a melasma quality of life questionnaire for the Turkish language:
      the MelasQoL-TR study.
AB  - OBJECTIVES: In this study, the objective was to evaluate the validity and
      reliability of the Turkish version of the melasma quality of life questionnaire
      (MelasQoL-Tr) for melasma patients. METHODS: The study included 114 melasma
      patients. The melasma area and severity index (MASI), MelasQoL-Tr and the Turkish
      short version of the QoL assessment instrument from the World Health Organization
      (WHOQOL-BREF) were used to assess melasma severity and QoL at baseline. The
      reliability and validity of MelasQoL-Tr were computed. RESULTS: The mean age of
      the patients in the study was 31.8 +/- 7.3 years. The internal consistency of the
      scale (Cronbach's alpha coefficient) was 0.88. The MelasQoL-Tr score was 29.9 +/-
      14.6 (range 10-66). The total WHOQOL-BREF score was 54.8 +/- 9.8. The comparison
      of MelasQoL-Tr and WHOQOL-BREF questionnaires showed an inverse significant
      correlation on total scores, which indicated a sufficient convergent validity.
      According to the subscale of WHOQOL-BREF, the inverse correlation was most
      significant between the MelasQoL-Tr score and psychological domain and less
      significant between the MelasQoL-Tr score and environmental domain. The MelasQoL
      Tr score and MASI were significantly correlated. CONCLUSION: The Turkish version
      of the MelasQoL was valid and reliable for evaluating the quality of life of
      Turkish melasma patients.

PMID- 18720187
TI  - A case of non-Hodgkin's lymphoma-associated pemphigus foliaceus and use of
      rituximab for treatment.
AB  - BACKGROUND: Pemphigus foliaceus (PF), an autoimmune skin disorder resulting in
      the formation of superficial blisters, is a rarely reported skin manifestation of
      non-Hodgkin's lymphoma (NHL). Typical therapies for PF in non-malignant cases
      include immunosuppressants such as corticosteroids. We report the case of a
      patient undergoing therapy for NHL who subsequently developed PF which resolved
      following treatment with rituximab, an anti-CD20 monoclonal antibody. CASE
      REPORT: A 73-year-old Caucasian male who received a course of rituximab for NHL 3
      years prior, presented with atypical urticarial lesions that developed into
      blisters. Pathological determination identified the lesions as PF. Traditional
      corticosteroid therapy failed to resolve the PF lesions. However, in this
      clinical situation, the patient responded to a repeat rituximab administration
      with complete resolution of the PF lesions. DISCUSSION: Paraneoplastic pemphigus,
      the most serious form of pemphigus, is more commonly associated with
      malignancies, such as NHL, whereas PF is seen in non-malignant cases. Although
      our patient was undergoing therapy for a malignancy, the less severe pemphigus
      emerged and responded to a non-traditional therapy. As such, we recommend that
      consideration is given to alternative therapies, including monoclonal antibodies,
      in cases of PF with atypical presentations and pathology associated with
      malignancy.

PMID- 18720188
TI  - A potential role of alkaloid extracts from Salsola species (Chenopodiaceae) in
      the treatment of Alzheimer's disease.
AB  - From the aerial parts of Salsola oppositofolia, S. soda and S. tragus an alkaloid
      extract was obtained and tested to evaluate antioxidant and anti-cholinesterase
      activities. The in vitro study of the antioxidant activity by the DPPH method
      revealed a significant activity of Salsola alkaloid extracts with IC(50) values
      ranging from 16.30 microg/mL for S. oppositifolia to 26.17 microg/mL for S.
      tragus. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory
      activities were evaluated. S. tragus alkaloid extract exerted the highest
      inhibitory activity against AChE (IC(50) of 30.2 microg/mL) and BChE (IC(50) of
      26.5 microg/mL). Interestingly, S. soda and S. oppositifolia exhibited a
      selective inhibitory activity against BChE with IC(50) values of 34.3 microg/mL
      and 32.7 microg/mL, respectively. Tetrahydroisoquinoline alkaloids were
      identified and quantified by GC/MS analysis.

PMID- 18720189
TI  - In vitro anti-leishmanial activities of germatranyl and Silicon incorporated
      diorganotin derivatives: synthesis and spectroscopic properties.
AB  - A series of germanium and silicon incorporated diorganotin derivatives of general
      formula [N(OCH2CH2)3GeCH(R(1)CH2CO2]2 SnR2(2) where R1 = H3C, C6H5, p-CH3C6H4, p
      FC6H4; R2 = H2CSi(CH3)2C6H5, H2CC6H5, p-CH3C7H7 were synthesized by the reaction
      of appropriate diorganotin dichlorides and germatranyl (substituted) propionic
      acid in 1:2 mole ratio, respectively. The evidence regarding their structure is
      mainly based on spectroscopic data obtained by multinuclear (1H, 13C, 29Si,
      119Sn) NMR and 119mSn Mossbauer, IR and mass spectral studies in combination with
      melting points and elemental analyses. The compounds have been screened for in
      vitro anti-leishmanial activity against promastigotes of Leishmania major and the
      results offer potent activities which are better than the standard drug,
      pentamidine, for one compound.

PMID- 18720190
TI  - Synthesis of functionalized amino acid derivatives as new pharmacophores for
      designing anticancer agents.
AB  - A new series of functionalized amino acid derivatives N-substituted 1-N-(tert
      butoxycarbonyl)-2,2-dimethyl-4-phenyl-5-oxazolidine carboxamide (1-17) and 1-N
      substituted-3-amino-2-hydroxy-3-phenylpropane-1-carboxamide (18-34) were
      synthesized and evaluated for their in vitro cytotoxicity against human cancer
      cell lines. Compound 6 has shown interesting cytotoxicity (IC(50) = 5.67 microm)
      in ovarian cancer, while compound 10 exhibited promising cytotoxicity in ovarian
      (IC(50) = 6.1 microm) and oral (IC(50) = 4.17 microm) cancers. These compounds
      could be of use in designing new anti-cancer agents.

PMID- 18720191
TI  - Anti-oxidant, in vitro, in vivo anti-inflammatory activity and antiproliferative
      activity of mefenamic acid and its metal complexes with manganese(II),
      cobalt(II), nickel(II), copper(II) and zinc(II).
AB  - Some new complexes of mefenamic acid with potentially interesting biological
      activity are described. The complexes of mefenamic acid [Mn(mef)(2)(H(2)O)(2)],
      1, [Co(mef)(2)(H(2)O)(2)], 2, [Ni(mef)(2)(H(2)O)(2)], 3, [Cu(mef)(2)(H(2)O)](2),
      4 and [Zn(mef)(2)], 5, were prepared by the reaction of mefenamic acid, a potent
      anti-inflammatory drug with metal salts. Optical and infrared spectral data of
      these new complexes are reported. Monomeric six-coordinated species were isolated
      in the solid state for Mn(II), Ni(II) and Co(II), dimeric five-coordinated for
      Cu(II) and monomeric four-coordinated for Zn(II). In DMF or CHCl(3) solution the
      coordination number is retained and the coordinated molecules of water are
      replaced by solvent molecules. The anti-oxidant properties of the complexes were
      evaluated using the 1,1-diphenyl-2-picrylhydrazyl, DPPH, free radical scavenging
      assay. The scavenging activities of the complexes were measured and compared with
      those of the free drug and vitamin C. We have explored their ability to inhibit
      soybean lipoxygenase, beta-glucuronidase and trypsin- induced proteolysis. The
      complex [Mn(mef)(2)(H(2)O)(2)] exhibits the highest antioxidant activity and the
      highest inhibitory effect against the soybean lipogygenase (LOX), properties that
      are not demonstrated by mefenamic acid. Their inhibitory effects on rat paw edema
      induced by Carrageenan was studied and compared with those of mefenamic acid. The
      complex [Zn(mef)(2)] exhibited a strong inhibitory effect at 0.1 mmol/Kg B.W.
      (81.5 +/- 1.3% inhibition), superior to the inhibition induced by mefenamic acid
      at the same dose (61.5 +/- 2.3% inhibition). Mefenamic acid and its metal
      complexes have been evaluated for antiproliferative activity in vitro against the
      cells of three human cancer cell lines: MCF-7 (human breast cancer cell line),
      T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse
      fibroblast L-929 cell line. The copper(II) complex displays against T24, MCF-7
      and L-929 cancer cell lines, IC(50) values in a microM range similar to that of
      the antitumor drug cis-platin and they are considered for further stages of
      screening in vitro and/or in vivo as agents with potential antitumor activity.

PMID- 18720192
TI  - Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated
      molecular docking and subsequent in vitro/in vivo evaluation.
AB  - Curcumin was investigated as an inhibitor of glycogen synthase kinase-3beta (GSK
      3beta) in an attempt to explain some of its interesting multiple pharmacological
      effects, such as its anti-diabetic, anti-inflammatory, anti-cancer, anti-malarial
      and anti-alzheimer's properties. The investigation included simulated docking
      experiments to fit curcumin within the binding pocket of GSK-3beta followed by
      experimental in vitro and in vivo validations. Curcumin was found to optimally
      fit within the binding pocket of GSK-3beta via several attractive interactions
      with key amino acids. Experimentally, curcumin was found to potently inhibit GSK
      3beta (IC50 = 66.3 nM). Furthermore, our in vivo experiments illustrated that
      curcumin significantly increases liver glycogen in fasting Balb/c mice. Our
      findings strongly suggest that the diverse pharmacological activities of curcumin
      are at least partially mediated by inhibition of GSK-3beta.

PMID- 18720193
TI  - Quantitative structure-activity relationship (QSAR) studies on a series of 1,3,4
      thiadiazole-2-thione derivatives as tumor-associated carbonic anhydrase IX
      inhibitors.
AB  - A linear quantitative structure-activity relationship (QSAR) study that encodes
      various aspects of physicochemical, topological and electronic descriptors has
      been developed for a series of 1,3,4-thiadiazole-2-thione derivatives (1a-r and
      2a-c). The carbonic anhydrase IX inhibitory activity of the candidates under
      study (1a-r and 2a-c) were correlated to the selected parameters using stepwise
      linear regression analyses to achieve the best QSAR model. Promising results were
      obtained with the employed tetra-parametric model indicating that the information
      approach used in the present investigation is quite useful for modeling carbonic
      anhydrase IX inhibitors.

PMID- 18720195
TI  - Liposome-mediated triggering of complement cascade.
AB  - The complement system is one of the most ancient defense strategies, which serves
      as an important effector arm of both innate and acquired immunity. Three
      consequences ensue when liposomes trigger the complement system in the blood.
      These are priming of the vesicular surface by opsonic complement fragments for
      recognition and clearance by phagocytic cells, generation of anaphylatoxins, and
      chemoattractants, which may subsequently initiate pseudoallergy-related
      anaphylaxis in sensitive individuals, and insertion of the lytic complex C5b-9
      into the liposomal bilayer, which may result in substantial leakage of vesicular
      encapsulated aqueous cargo. Here, we briefly review and discuss the molecular
      basis of complement activation by phospholipid vesicles and reflect on sensitive
      and rapid Enzyme-Linked Immunosorbent Assays (ELISA) for assessing and monitoring
      liposome-mediated triggering of a complement cascade in human serum.

PMID- 18720194
TI  - Synthesis, acoustic stability, and pharmacologic activities of papaverine-loaded
      echogenic liposomes for ultrasound controlled drug delivery.
AB  - BACKGROUND: development of encapsulated therapeutics that could be released upon
      ultrasound exposure has strong implications for enhancing drug effects at the
      target site. We have developed echogenic liposomes (ELIP) suitable for ultrasound
      imaging of blood flow and ultrasound-mediated intravascular drug release.
      Papaverine was chosen as the test drug because its clinical application requires
      high concentration in the target vascular bed but low concentration in the
      systemic circulation. METHODS: the procedure for preparation of standard ELIP was
      modified by including Papaverine hydrochloride in the lipid hydration solution,
      followed by three freeze-thaw cycles to increase encapsulation of the drug.
      Sizing and encapsulation pharmacokinetics were performed using a Coulter counter
      and a phosphodiesterase activity assay. Stability of Papaverine-loaded ELIP
      (PELIP) was monitored with a clinical diagnostic ultrasound scanner equipped with
      a linear array transducer at a center frequency of 4.5 MHz by assessing the mean
      digital intensity within a region of interest over time. The stability of PELIP
      was compared to those of standard ELIP and Optison. RESULTS: relative to standard
      ELIP, PELIP were larger (median diameter = 1.88 +/- 0.10 microm for PELIP vs 1.08
      +/- 0.15 microm for ELIP) and had lower Mean Gray Scale Values (MGSV) (92 +/-
      24.8 for PELIP compared to 142.3 +/- 10.7 for ELIP at lipid concentrations of 50
      microg/ml). The maximum loading efficiency and mean encapsulated concentration
      were 24% +/- 7% and 2.1 +/- 0.7 mg/ml, respectively. Papaverine retained its
      phosphodiesterase inhibitory activity when associated with PELIP. Furthermore, a
      fraction of this activity remained latent until released by dissolution of
      liposomal membranes with detergent. The stability of both PELIP and standard ELIP
      were similar, but both are greater than that of Optison. CONCLUSIONS: our results
      suggest that PELIP have desirable physical, biochemical, biological, and acoustic
      characteristics for potential in vivo administration and ultrasound-controlled
      drug delivery.

PMID- 18720196
TI  - Formulation and characterization of the microencapsulated entomopathogenic fungus
      Metarhizium anisopliae MA126.
AB  - Bioinsecticides are expected to be used for controlling major species of aphids.
      The present study explored a liquid phase coating technique for the formulation
      of microencapsulated conidia of the entomopathogenic fungus Metarhizium
      anisopliae MA126. Various parameters for microencapsulation were investigated.
      The biopolymers sodium alginate, hydroxypropyl methyl cellulose (HPMC) and
      chitosan were tested as coating materials. Calcium chloride was used as the cross
      linking agent for converting soluble sodium alginate into an insoluble form. To
      improve the efficiency of microencapsulation, the additives of HPMC, dextrin,
      chitosan or HPMC/chitosan in various ratios (1 : 1, 1 : 3 and 3 : 1) were used as
      the coating materials. The particle size of a bare microcapsule was less than 30
      microm. Larger size microcapsules were produced using vortex method by comparison
      with that using homogenization method. The latter method, however, was easy to
      scale up. The effect of coating materials on the morphology and encapsulation
      efficiency of the microcapsules was also studied. The best encapsulation
      efficiency (78%) was using HPMC as the additive of the coating material. The next
      was dextrin (70%). By measuring the germination rate, the results showed that the
      activity was approximately 80% of the initial after 6 months of storage at 4
      degrees C, while that of the bare conidia was less than 50% stored in identical
      conditions.

PMID- 18720197
TI  - Evaluation of proniosomes as an alternative strategy to optimize piroxicam
      transdermal delivery.
AB  - The current investigation aims to evaluate the transdermal potential of niosomes
      bearing a potent non-steroidal anti-inflammatory, piroxicam. Piroxicam-loaded
      niosomes were prepared and characterized for surface morphology, entrapment
      efficiency and in vitro permeation across excised rat skin from various
      proniosome gel formulations using Franz diffusion cells. Various non-ionic
      surfactants were used to achieve optimum encapsulation efficiency. The prepared
      proniosomes significantly improved drug permeation and reduced the lag time (p <
      0.05). Proniosomes prepared with Span 60 provided a higher piroxicam flux across
      the skin than did those prepared with Tween 80. Niosomes prepared using Span 60
      showed a higher release rate than those prepared using non-ionic surfactants,
      Span 20 and Span 80, while those prepared from Tween showed higher release rate
      than formula prepared with Span. This indicates that lipophilicity and
      hydrophilicity of surfactant has a main role in release rates of piroxicam.
      Particle size of piroxicam niosomal vesicles formed by proniosome was determined
      by scanning electron microscopy. The encapsulation efficiency was evaluated by a
      specific high performance liquid chromatography method. Niosomes formed from
      using Spans and Tweens exhibited very high encapsulation efficiency. The results
      are very encouraging and suggest that niosomes can act as promising carriers
      offering an alternative approach for transdermal delivery of piroxicam.

PMID- 18720198
TI  - Influence of morphology and drug distribution on the release process of FITC
      dextran-loaded microspheres prepared with different types of PLGA.
AB  - The aim of the present work was to understand the collaborative roles and the
      comprehensive effects of polymer nature, morphology, drug distribution and
      release behaviour for PLGA microspheres prepared by the double emulsion method.
      The morphology and drug distribution of the FITC-dextran-loaded microspheres were
      investigated by scanning electron microscopy (SEM) and confocal laser scanning
      microscopy (CLSM), respectively. The results show that the morphology and release
      profiles depend on the polymer nature. For the capped PLGA RG502, the porosity,
      pore size and drug distribution had no pronounced influence on the release
      profile beyond the initial release. No significant changes in size and morphology
      were found and there was negligible water uptake during the release process. PEG
      addition as a pore maker indicated a possible way to modify the release rate at
      the second release stage. However, in the case of the uncapped PLGA RG503H,
      release profiles were dependent upon changes in porosity, pore size and drug
      loading. Increases in porosity, internal pore size and loading resulted in a
      continuous release profile. Previous studies have shown the importance of
      different process parameters on morphology and drug release, but in this work it
      is clear that polymer nature is a determining factor.

PMID- 18720199
TI  - Formulation and evaluation of stomach-specific amoxicillin-loaded carbopol-934P
      mucoadhesive microspheres for anti-Helicobacter pylori therapy.
AB  - The purpose of this research was to formulate and systemically evaluate in vitro
      and in vivo performances of mucoadhesive amoxicillin microspheres for the
      potential use in the treatment of gastric and duodenal ulcers, which were
      associated with Helicobacter pylori. Amoxicillin mucoadhesive microspheres
      containing carbopol-934P as mucoadhesive polymer and ethyl cellulose as carrier
      polymer were prepared by an emulsion-solvent evaporation technique. Results of
      preliminary trials indicate that quantity of emulsifying agent, time for
      stirring, drug-to-polymers ratio and speed of rotation affected the
      characteristics of microspheres. Microspheres were discrete, spherical, free
      flowing and showed a good percentage of drug entrapment efficiency. An in vitro
      mucoadhesive test showed that amoxicillin mucoadhesive microspheres adhered more
      strongly to the gastric mucous layer and could retain in the gastrointestinal
      tract for an extended period of time. A 3(2) full factorial design was employed
      to study the effect of independent variables, drug-to-polymer-to-polymer ratio
      (amoxicillin-ethyl cellulose-carbopol-934P) (X(1)) and stirring speed (X(2)) on
      dependent variables, i.e. percentage mucoadhesion, drug entrapment efficiency,
      particle size and t(80). The best batch exhibited a high drug entrapment
      efficiency of 56%; mucoadhesion percentage after 1 h was 80% and the particle
      size was 109 um. A sustained drug release was obtained for more than 12 h. The
      drug-to-polymer-to-polymer ratio had a more significant effect on the dependent
      variables. The morphological characteristics of the mucoadhesive microspheres
      were studied under a scanning electron microscope. In vitro release test showed
      that amoxicillin released slightly faster in pH 1.2 hydrochloric acid than in pH
      7.8 phosphate buffer. In vivo H. pylori clearance tests were also carried out by
      administering amoxicillin powder and mucoadhesive microspheres to H. pylori
      infectious Wistar rats under fed conditions at single dose or multiple dose(s) in
      oral administration. The results showed that amoxicillin mucoadhesive
      microspheres had a better clearance effect than amoxicillin powder. In
      conclusion, the prolonged gastrointestinal residence time and enhanced
      amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin
      might make a contribution to H. pylori complete eradication.

PMID- 18720200
TI  - Lacidipine encapsulated gastroretentive microspheres prepared by chemical
      denaturation for pylorospasm.
AB  - The purpose of this research work was to formulate and systematically evaluate in
      vitro performance of mucoadhesive microspheres of lacidipine for treatment of
      pylorospasm. Lacidipine microspheres containing chitosan were prepared by
      chemical denaturation using glutaraldehyde as a cross-linking agent. The
      microspheres were evaluated for physical characteristics such as particle size,
      particle shape and surface morphology by scanning electron microscopy, drug
      entrapment efficiency and in vitro mucoadhesion. Results of preliminary trials
      indicated that the polymer concentration, cross-linking agent and stirring speed
      had a noticeable effect on size and surface morphology. A central composite
      design was employed to study the effect of independent variables, polymer
      concentration (X(1)), volume of glutaraldehyde (X(2)), stirring speed (X(3)) and
      cross-linking time (X(4)) on dependent variables, drug entrapment efficiency and
      percentage mucoadhesion. The entrapment efficiency varied from 14-40.82%
      depending upon the polymer concentration, volume of cross-linker and stirring
      speed. All batches of microspheres exhibited good mucoadhesive property (73-83%)
      in the in vitro wash-off test. It was observed that polymer concentration and
      glutaraldehyde volume had a more significant effect on the dependent variables.
      Maximum entrapment (36.53%) and mucoadhesion (81.33%) was predicted at 3.5%
      chitosan, 3 ml glutaraldehyde, 3000 rpm stirring speed and 75 min cross-linking
      time under optimized process condition. The selected formulation showed
      controlled release for more than 6 h. The release followed Higuchi kinetics via a
      Fickian diffusion.

PMID- 18720201
TI  - Biomechanical comparison of the double-push technique and the conventional skate
      skiing technique in cross-country sprint skiing.
AB  - The aims of the study were to: (1) adapt the "double-push" technique from inline
      skating to cross-country skiing; (2) compare this new skiing technique with the
      conventional skate skiing cross-country technique; and (3) test the hypothesis
      that the double-push technique improves skiing speed in a short sprint. 13 elite
      skiers performed maximum-speed sprints over 100 m using the double-push skate
      skiing technique and using the conventional "V2" skate skiing technique. Pole and
      plantar forces, knee angle, cycle characteristics, and electromyography of nine
      lower body muscles were analysed. We found that the double-push technique could
      be successfully transferred to cross-country skiing, and that this new technique
      is faster than the conventional skate skiing technique. The double-push technique
      was 2.9 +/- 2.2% faster (P < 0.001), which corresponds to a time advantage of
      0.41 +/- 0.31 s over 100 m. The double-push technique had a longer cycle length
      and a lower cycle rate, and it was characterized by higher muscle activity,
      higher knee extension amplitudes and velocities, and higher peak foot forces,
      especially in the first phase of the push-off. Also, the foot was more loaded
      laterally in the double-push technique than in the conventional skate skiing
      technique.

PMID- 18720202
TI  - Effects of 72-h of exercise abstinence on affect and body dissatisfaction in
      healthy female regular exercisers.
AB  - In this study, we compared the effects of a 72-h exercise abstinence period and
      normal exercise on the affect and body dissatisfaction of 58 healthy women (mean
      age 26.1 years, s = 8.2) who exercised at least four times per week, and explored
      the relationship between the changes in affect and body dissatisfaction.
      Participants completed the UWIST-MACL and Body Dissatisfaction Scale to assess
      affect and body image, and were randomized to an abstinence or control group.
      Affect and body image for both groups were re-assessed following the 72-h
      abstinence period. Compared with the control group, the abstinence group had a
      significant decrease in hedonic tone and energetic arousal, and a significant
      increase in tense arousal and body dissatisfaction from pre-intervention to post
      intervention. There were no significant relationships between the changes in body
      dissatisfaction and the components of affect. A 72-h exercise abstinence period
      resulted in increased affect disturbance and body dissatisfaction in regularly
      active women.

PMID- 18720203
TI  - Sport and exercise science: just how new is new?

PMID- 18720204
TI  - Physiological responses to 1000-m ergometer time-trial performance in outrigger
      canoeing.
AB  - Graded exercise tests are commonly used to assess peak physiological capacities
      of athletes. However, unlike time trials, these tests do not provide performance
      information. The aim of this study was to examine the peak physiological
      responses of female outrigger canoeists to a 1000-m ergometer time trial and
      compare the time-trial performance to two graded exercise tests performed at
      increments of 7.5 W each minute and 15 W each two minutes respectively. 17
      trained female outrigger canoeists completed the time trial on an outrigger canoe
      ergometer with heart rate (HR), stroke rate, power output, and oxygen consumption
      (VO2) determined every 15 s. The mean (+/- s) time-trial time was 359 +/- 33 s,
      with a mean power output of 65 +/- 16 W and mean stroke rate of 56 +/- 4 strokes
      min(-1). Mean values for peak VO2, peak heart rate, and mean heart rate were 3.17
      +/- 0.67 litres min(-1), 177 +/- 11 beats min(-1), and 164 +/- 12 beats min(-1)
      respectively. Compared with the graded exercise tests, the time-trial elicited
      similar values for peak heart rate, peak power output, peak blood lactate
      concentration, and peak VO2. As a time trial is sport-specific and can
      simultaneously quantify sprint performance and peak physiological responses in
      outrigger canoeing, it is suggested that a time trial be used by coaches for crew
      selection as it doubles as a reliable performance measure and a protocol for
      monitoring peak aerobic capacity of female outrigger canoeists.

PMID- 18720205
TI  - The performance environment of the England youth soccer teams: a quantitative
      investigation.
AB  - We examined the performance environment of the England youth soccer teams. Using
      a conceptually grounded questionnaire developed from the themes identified by
      Pain and Harwood (2007), 82 players and 23 national coaches and support staff
      were surveyed directly following international tournaments regarding the factors
      that positively and negatively influenced performance. The survey enabled data to
      be captured regarding both the extent and magnitude of the impact of the factors
      comprising the performance environment. Overall, team and social factors were
      generally perceived to have the greatest positive impact, with players and staff
      showing high levels of consensus in their evaluations. Team leadership and strong
      team cohesion were identified by both groups as having the greatest positive
      impact. Overall, far fewer variables were perceived to have a negative impact on
      performance, especially for players. The main negatives common to both groups
      were players losing composure during games, player boredom, and a lack of
      available activities in the hotel. The major findings support those of Pain and
      Harwood (2007) and in using a larger sample helped to corroborate and strengthen
      the generalizability of the findings.

PMID- 18720208
TI  - Schizotypy and handedness in Japanese participants, revisited.
AB  - Although previous studies have suggested a relationship between mixed-handedness
      and schizotypic symptoms, possibly indicating a predisposition to schizophrenia,
      the participants involved were exclusively from Western cultures. Only two
      reports have examined the relationship between handedness and schizotypy in Asian
      cultures, and both of these studies failed to show a significant association
      between mixed-handedness and schizotypy, possibly due to cultural pressures
      against left-handedness. In the present study we examined the relationship
      between handedness and schizotypy among Japanese participants (N=231, study 1;
      N=274, study 2). In order to avoid cultural biases, we used a modified handedness
      scale in addition to the traditional scale developed in Western cultures. As a
      result, we show for the first time that mixed-handed Japanese participants have
      the strongest schizotypal traits, particularly positive schizotypic traits
      (p<.05). These results suggest that positive schizotypal traits may be
      universally associated with mixed-handedness or atypical cerebral lateralisation,
      even in non-Western cultures.

PMID- 18720207
TI  - Hand preference and skilled hand performance among individuals with successful
      rightward conversions of the writing hand.
AB  - Searleman and Porac (2001) studied lateral preference patterns among successfully
      switched left-hand writers, left-hand writers with no switch pressure history,
      and left-hand writers who did not switch when pressured. They concluded that left
      handers who successfully shift to right-hand writing are following an inherent
      right-sided lateralisation pattern that they already possess. Searleman and Porac
      suggested that the neural mechanisms that control lateralisation in the
      successfully switched individuals are systematically different from those of
      other groups of left-handers. I examined patterns of skilled and less-skilled
      hand preference and skilled hand performance in a sample of 394 adults (ages 18
      94 years). The sample contained successfully switched left-hand writers, left
      handers pressured to shift who remained left-hand writers, left-handers who did
      not experience shift pressures, and right-handers. Both skilled hand preference
      and skilled hand performance were shifted towards the right side in successfully
      switched left-hand writers. This group also displayed mixed patterns of hand
      preference and skilled hand performance in that they were not as right-sided as
      "natural" right-handers nor were they as left-sided as the two left-hand writing
      groups, which did not differ from each other. The experience of being pressured
      to switch to right-hand writing was not sufficient to shift lateralisation
      patterns; the pressures must be experienced in the context of an underlying
      neural control mechanism that is amenable to change as a result of these external
      influences.

PMID- 18720209
TI  - The influence of classical dance training on preferred supporting leg and whole
      body turning bias.
AB  - A rightward turning bias has been more frequently noted during adult classical
      dance practice than during spontaneous rotations. Training could play a role in
      inducing a preferred direction. We observed the preferred direction for executing
      four spontaneous whole-body full turns (pirouettes), with eyes open or closed, in
      pre-pubertal untrained girls and classical dance students. Of untrained girls,
      58% showed a leftward turning bias (LTB) and 42% a rightward turning bias (RTB),
      independently of vision, lateral preferences, and supporting leg. Only one dancer
      showed a consistent LTB while the majority showed a RTB, with a tendency to use
      the left leg to turn towards the right. These results suggest that the role of
      the vestibular and visual systems is minimal for untrained girls, and suggest a
      training influence for dancers. The dance students' choice of a supporting leg
      for turning may exploit some biomechanical properties facilitating the pirouette.

PMID- 18720210
TI  - Plasmablastic lymphoma with small lymphocytic lymphoma: clinico-pathologic
      features, and review of the literature.

PMID- 18720211
TI  - Paraneoplastic lumbosacral axonal polyradiculopathy preceding the diagnosis of
      nodular lymphocyte predominant Hodgkin lymphoma: a case report.

PMID- 18720212
TI  - The incidence of JAK2 V617F mutation in bcr/abl-negative chronic
      myeloproliferative disorders: assessment by two different detection methods.
AB  - A recurrent specific JAK2 V617F mutation has been reported in bcr/abl-negative
      chronic myeloproliferative diseases (cMPD), including polycythemia vera (PV),
      essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). The mutation
      is detectable in a variable proportion of neoplastic clones, depending on the
      molecular methods employed. In this study, we attempted to establish the JAK2
      V617F mutation frequency in two partially overlapping cMPD patient series by two
      different PCR-based techniques. Using an allele-specific polymerase chain
      reaction assay (AS-PCR), the JAK2 V617F mutation was detected in 124/158 (78.5%)
      cMPD patients; in particular, 90.2, 72.1, 63.2 and 50% of PV, ET, IMF and
      unclassified (U)-MPD cases, respectively, showed the mutation. Employing a
      semiquantitative 5' fluorogenic TaqMan assay, the JAK2 V617F mutation was
      identified in a much larger percentage of cMPDs patients (118/127: 92.9%). Rates
      of mutation in PV, ET, IMF and U-MPD cases were 95.9, 85.7, 91.7 and 92.9%,
      respectively. Furthermore, a statistically higher percentage of JAK2 mutated
      alleles was detected by TaqMan assay in PV (68+/-3.5, mean value+/-SEM) and IMF
      (64+/-9.3) cases as compared with ET (35+/-5.4). Finally, a significant
      correlation between JAK2 V617F mutational status and hematocrit (Ht), white blood
      cell and platelet counts in PV patients, and Ht values in ET cases, was observed
      by AS-PCR. Overall, these data indicate that TaqMan technology significantly
      improved sensitivity in detecting the JAK2 mutation in cMPD patients and may be
      worth of further evaluations as a clinically useful tool for detection of small
      amounts of mutated clones.

PMID- 18720213
TI  - Bortezomib, doxorubicin and dexamethasone association is an effective option for
      plasma cell leukemia induction therapy.

PMID- 18720214
TI  - Not just sound: supplementing the voice range profile with the singer's own
      perceptions of vocal challenges.
AB  - A commercial phonetograph was complemented with a response button, such that
      presses resulted in marked regions in the voice range profile (VRP). This study
      reports the VRP data of 16 healthy female professionally trained singers (7 mezzo
      sopranos and 9 sopranos). Subjects pressed the button to indicate sensations of
      vocal instability or reduced control during phonation. Each press thereby marked
      potential areas of difficulty. A method is presented to quantify the consistency
      of button use for repeated tasks. The pattern of button presses was significantly
      consistent within subjects. As expected, the singers pressed at the extremes of
      VRP contours as well as at register transitions. These results and the potential
      of the method for the assessment of vocal problems of singers are discussed.

PMID- 18720215
TI  - Clinical aspergillosis for basic scientists.
AB  - Aspergilli are ubiquitous, and can cause a variety of allergic disorders and
      invasive infections. These various manifestations of the diseases, diagnosis and
      treatment are organized for basic scientists, so that they may better understand
      the dimensions and nature of the clinical challenges.

PMID- 18720216
TI  - Role of (1-->3)-beta-D-glucan in the diagnosis of invasive aspergillosis.
AB  - Measurement of serum (1-->3)-beta-D-Glucan (BG) is an aid in the diagnosis of
      fungemia and deep-seated mycoses, including invasive aspergillosis (IA). BG is
      present in the cell wall of most pathogenic fungi (including Pneumocystis
      jiroveci) in significant amounts with some notable exceptions such as
      Cryptococcus neoformans and Zygomycetes. Commercially available assays can detect
      serum BG concentrations as low as 1 pg/mL. Published validation studies have
      included patients with IA and other invasive fungal diseases (IFD). BG detection
      appears to be more sensitive than galactomannan detection in patients with IA,
      but BG's intrinsic lack of mycological specificity requires the integration of
      clinical, radiological, and microbiological data for proper interpretation. BG
      assay test characteristics can be used, for example, to exclude IA in some
      clinical scenarios, to increase the certainty of IA in the presence of an
      isolated positive galactomannan result or when testing follows initiation of
      antifungal treatment. BG may be falsely elevated in the serum in the absence of
      IFD in patients undergoing hemodialysis with cellulose membranes, in patients
      treated with immunoglobulin, albumin, or other blood products filtered through
      cellulose filters containing BG, and in patients with serosal exposure to glucan
      containing gauze or to certain intravenous antimicrobials. These potential
      sources of false positivity should be considered when interpreting BG results. BG
      may be useful as a sensitive screening tool for surveillance of IA and other IFD
      in populations at risk. Stratified IFD screening and diagnostic strategies using
      both galactomannan and BG should be explored. Factors affecting the production
      and clearance of BG during IA and other IFD need additional study to further
      refine its diagnostic utility.

PMID- 18720217
TI  - In vitro synergy of caspofungin with licensed and novel antifungal drugs against
      clinical isolates of Fusarium spp.
AB  - Combinations of caspofungin (CAS) with amphotericin-B (AMB), voriconazole (VRC),
      terbinafine (TRB) and tacrolimus (FK-506) were tested in vitro with 10 Fusarium
      isolates. MIC and minimal effective concentrations (MEC) were investigated in
      accord with the CLSI methodology. Drug interactions were assessed by the
      fractional inhibitory concentration index (FICI). Synergy occurred in 10/10,
      9/10, 7/10 and 4/10 isolates with CAS/FK-506, CAS/TRB, CAS/AMB and CAS/VRC,
      respectively. Caspofungin MECs reached clinically attainable concentrations with
      FK-506 and TRB. Hyphal length and DiBAC staining demonstrated enhanced inhibition
      and killing with CAS/FK-506 and CAS/TRB. The combination of CAS/TRB and CAS/FK
      506 is strongly synergistic in vitro against Fusarium spp. Our finding should be
      further studied in animal models of invasive infections caused by this fungus.

PMID- 18720218
TI  - Cladophialophora saturnica sp. nov., a new opportunistic species of
      Chaetothyriales revealed using molecular data.
AB  - While many members of the black yeasts genus Cladophialophora have been reported
      to cause diseases in humans, understanding of their natural niche is frequently
      lacking. Some species can be recovered from the natural environment by means of
      selective isolation techniques. The present study focuses on a Cladophialophora
      strain that caused an interdigital tinea nigra-like lesion in a HIV-positive
      Brazilian child. The fungal infection was successfully treated with oxiconazole.
      Similar strains had been recovered from the environment in Brazil, Uruguay and
      the Netherlands. The strains were characterized by sequencing the Internal
      Transcribed Spacer (ITS) regions and the small subunit (SSU) of the nuclear
      ribosomal RNA gene, as well as the elongation factor 1-alpha (EF1alpha) gene.
      Since no match with any known species was found, it is described as the new
      species, Cladophialophora saturnica.

PMID- 18720219
TI  - Pictorial encoding effects and memory confusions in the Deese-Roediger-McDermott
      paradigm: evidence for the activation of spontaneous imagery.
AB  - The purpose of the experiments reported in this paper was to examine the possible
      role of spontaneous imagery and list-specific cues on pictorial encoding effects
      induced by the Deese-Roediger-McDermott (DRM) task. After viewing pictures and
      words referring to thematically related materials, by way of a picture/word
      source-judgement task, participants were asked to remember the way in which these
      materials were presented. Participants reported "seeing" pictures of items that
      were presented as words, an effect predicted by the imaginal activation
      hypothesis in its suggestion that incidental images experienced during encoding
      will later be mistaken as memories for pictures. Whether participants made the
      same picture misattributions on related lures (or non-presented related items)
      depended on the way in which the lures' respective thematic lists were
      experienced during encoding (Experiments 1 and 2), pointing to the effects of
      list-specific cues in picture/word judgements. These findings have intriguing
      implications for interpretations of picture-encoding effects induced by the DRM
      task. The findings also speak to the use of DRM false-memory rates when
      marshalling evidence against the use of imagery in applied settings.

PMID- 18720220
TI  - Differentiated forgetting rates of spatial knowledge in humans in the absence of
      repeated testing.
AB  - Spatial knowledge, necessary for efficient navigation, comprises route knowledge
      (memory of the landmarks along a route) and survey knowledge (map-like).
      Available data on the retention in humans of spatial knowledge show that this
      does not decline systematically over months or years. Here, two groups of
      participants elaborated route and survey knowledge during navigation in a complex
      virtual environment before performing route and survey tasks. Both groups were
      tested 5 minutes after learning and 3 months later, while one group was also
      tested 1 week and 1 month later (repeated testing). Performance was similar in
      both groups on the first testing session, remained stable in the repeated tested
      group, but decreased in the non-repeated tested group, especially on route tasks.
      These results are the first to reveal a substantial and selective decline of
      spatial knowledge, occurring only if there is no possibility of reactivating
      knowledge along repeated testing.

PMID- 18720221
TI  - When we feel good and bad about ourselves: self-esteem memories across cultures.
AB  - Young adults in the United States, Croatia, and China described personal episodes
      of times when they felt especially good or bad about themselves. These self
      esteem memories were either recent (episodes that occurred during the previous 4
      weeks) or remote (episodes that occurred between the ages of 10 and 15).
      Systematic content differences between memories of positive and negative self
      worth were apparent primarily for remote rather than for recent memories. Across
      cultures, long-lasting positive memories frequently represented achievement
      themes, whereas negative memories frequently represented social themes. Links
      between achievement success and positive self-regard, and between social distress
      and negative self-regard, are explained using theories of self-esteem and
      autobiographical memory.

PMID- 18720222
TI  - Dissociating word stem completion and cued recall as a function of divided
      attention at retrieval.
AB  - The aim of this study was to investigate the widely held, but largely untested,
      view that implicit memory (repetition priming) reflects an automatic form of
      retrieval. Specifically, in Experiment 1 we explored whether a secondary task
      (syllable monitoring), performed during retrieval, would disrupt performance on
      explicit (cued recall) and implicit (stem completion) memory tasks equally.
      Surprisingly, despite substantial memory and secondary costs to cued recall when
      performed with a syllable-monitoring task, the same manipulation had no effect on
      stem completion priming or on secondary task performance. In Experiment 2 we
      demonstrated that even when using a particularly demanding version of the stem
      completion task that incurred secondary task costs, the corresponding disruption
      to implicit memory performance was minimal. Collectively, the results are
      consistent with the view that implicit memory retrieval requires little or no
      processing capacity and is not seemingly susceptible to the effects of dividing
      attention at retrieval.

PMID- 18720223
TI  - Manipulating recall vantage perspective of intrusive memories in dysphoria.
AB  - The current study attempted to experimentally manipulate mode of recall (field,
      observer perspective) in a sample of mildly dysphoric participants (N=134) who
      reported a distressing intrusive memory of negative autobiographical event.
      Specifically, the current study sought to ascertain whether shifting participants
      into a converse perspective would have differential effects on the reported
      experience of their memory. Results indicated that shifting participants from a
      field to an observer perspective resulted in decreased experiential ratings:
      specifically, reduced distress and vividness. Also, as anticipated, the converse
      shift in perspective (from observer to field) did not lead to a corresponding
      increase in experiential ratings, but did result in reduced ratings of
      observation and a trend was observed for decreased levels of detachment. The
      findings support the notion that recall perspective has a functional role in the
      regulation of intrusion-related distress and represents a cognitive avoidance
      mechanism.

PMID- 18720224
TI  - "Hotspots" in trauma memories in the treatment of post-traumatic stress disorder:
      a replication.
AB  - "Hotspots" refer to memories of detailed moments of peak emotional distress
      during a traumatic event. This study investigates hotspot frequency, and the
      emotions and cognitions contained in hotspots of memory for trauma, to replicate
      a previous study in this area (Holmes, Grey, & Young, 2005). Participants were
      patients receiving treatment for post-traumatic stress disorder (PTSD) at a
      specialist outpatient clinic after experiencing a range of traumatic events. The
      main finding was that, after fear, the most common emotions reported were anger
      and sadness. Cognitions related to psychological threat to the self were more
      common than those related to physical threat.

PMID- 18720225
TI  - Sickle red cell-endothelium interactions.
AB  - Periodic recurrence of painful vaso-occlusive crisis is the defining feature of
      sickle cell disease. Among multiple pathologies associated with this disease,
      sickle red cell-endothelium interaction has been implicated as a potential
      initiating mechanism in vaso-occlusive events. This review focuses on various
      interrelated mechanisms involved in human sickle red cell adhesion. We discuss in
      vitro and microcirculatory findings on sickle red cell adhesion, its potential
      role in vaso-occlusion, and the current understanding of receptor-ligand
      interactions involved in this pathological phenomenon. In addition, we discuss
      the contribution of other cellular interactions (leukocytes recruitment and
      leukocyte-red cell interaction) to vaso-occlusion, as observed in transgenic
      sickle mouse models. Emphasis is given to recently discovered adhesion molecules
      that play a predominant role in mediating human sickle red cell adhesion.
      Finally, we analyze various therapeutic approaches for inhibiting sickle red cell
      adhesion by targeting adhesion molecules and also consider therapeutic strategies
      that target stimuli involved in endothelial activation and initiation of
      adhesion.

PMID- 18720227
TI  - Theoretical modeling in hemodynamics of microcirculation.
AB  - Over the past decades, theoretical modeling has become an indispensable component
      of research into the hemodynamics of microcirculation. Numerous studies rely on
      modeling to provide quantitative insights into the interacting biophysical
      mechanisms that govern microcirculatory flow. The mechanical deformation of
      hematocytes has been addressed by continuum and molecular-informed computational
      models based on a growing body of experimental information. Theoretical analyses
      of single-vessel flow and blood rheology have led to a range of modeling
      approaches. Until recently, computational constraints limited direct simulations
      of multi-particle flows involving deformation and/or aggregation, but recent
      studies have begun to address this challenge. Network-level analyses have
      provided insights into the biophysical principles underlying the design of the
      microcirculation. This approach has been used to complement available
      experimental data and to derive empirical models of microvascular blood rheology.
      Continued increases in computational performance applied to current modeling
      techniques will enable larger scale simulations. In order to exploit this
      opportunity, integration of diverse theoretical approaches within a multi-scale
      framework is needed.

PMID- 18720226
TI  - Neutrophil recruitment under shear flow: it's all about endothelial cell rings
      and gaps.
AB  - Leukocyte recruitment to tissues and organs is an essential component of host
      defense. The molecular mechanisms controlling this process are complex and remain
      under active investigation. The combination of biochemical techniques and live
      cell imaging using in vivo and in vitro flow-model approaches have shed light on
      several aspects of neutrophil transmigration through the vascular endothelial
      lining of blood vessels. Here, we focus on the role of adhesion molecule
      signaling in endothelial cells and their downstream targets during the process of
      transendothelial migration at cell-cell borders (paracellular transmigration). An
      emerging model involves the leukocyte beta2 integrin engagement of endothelial
      cell ICAM-1, which triggers integrin-ICAM-1 clustering (rings) and stabilizes
      leukocyte adhesion at cell-cell junctions. This step recruits nonreceptor
      tyrosine kinases that phosphorylate key tyrosine residues in the cytoplasmic tail
      of VE-cadherin, which destabilizes its linkage to catenins and the actin
      cytoskeleton, triggering the transient opening of VE-cadherin homodimers to form
      a gap in the cell junction, through which the neutrophil transmigrates.
      Interestingly, the signaling events that lead to neutrophil transmigration occur
      independently of shear flow in vitro.

PMID- 18720228
TI  - Computational and mathematical modeling of angiogenesis.
AB  - Over the past two decades, a number of mathematical and computational models have
      been developed to study different aspects of angiogenesis that span the spatial
      and temporal scales encompassed by this complex process. For example, models have
      been built to investigate how growth factors and receptors signal endothelial
      cell proliferation, how groups of endothelial cells assemble into individual
      vessels, and how tumors recruit the ingrowth of whole microvascular networks. A
      prudent question to pose is: "what have we learned from these models?" This
      review aims to answer this question as it pertains to angiogenesis in the context
      of normal physiological growth, tumorigenesis, wound healing, tissue engineering,
      and the design of therapeutic strategies. We also provide a framework for parsing
      angiogenesis models into categories, according to the type of modeling approach
      used, the spatial and temporal scales simulated, and the overarching question
      being posed to the model. Finally, this review introduces some of the
      simplification strategies and assumptions used in model building, discusses model
      validation, and makes recommendations for application of modeling approaches to
      unresolved questions in the field.

PMID- 18720230
TI  - RBC adhesion to vascular endothelial cells: more potent than RBC aggregation in
      inducing circulatory disorders.
AB  - Growing evidence has suggested that the adhesion of red blood cells (RBCs) to
      blood vessel wall endothelial cells (ECs) is a potent catalyst of
      microcirculatory disorders, but direct in vivo documentation has been lacking. In
      a recent study we have demonstrated the elevation of vascular resistance by RBCs
      with increased adhesion to ECs and normal deformability in the absence of
      aggregation. Unlike the previous chapter (i.e., the "point"), the findings and
      considerations discussed in this chapter (the "counterpoint) imply that RBC/EC
      adhesion is a more potent determinant of circulatory disorders than RBC
      aggregation.

PMID- 18720231
TI  - The factorial validity and internal consistency of the Instrumental Activities of
      Daily Living Profile in individuals with a traumatic brain injury.
AB  - The objective of the study was to investigate the factorial validity and internal
      consistency of the Instrumental Activities of Daily Living (IADL) Profile. A
      group of 96 patients aged 16 to 65 years, with moderate to severe traumatic brain
      injuries, was recruited from 12 rehabilitation hospitals in Quebec. The IADL
      Profile was administered by an occupational therapist in each subject's home and
      community environment. Principal axis factoring and confirmatory factor analysis
      provide preliminary support for six correlated factors (F): (F1) going to grocery
      store/shopping for groceries, (F2) having a meal with guests/cleaning up, (F3)
      putting on outdoor clothing, (F4) obtaining information, (F5) making a budget,
      (F6) preparing a hot meal for guests. Total explained variance was 73.6%.
      Cronbach's alpha analysis revealed high to very high internal consistency for all
      scales ranging from .81 to .98; internal consistency of the total scale was very
      high (0.95). The findings suggest that the IADL Profile is a promising means of
      documenting both IADL independence and the repercussions of executive function
      deficits on everyday tasks in real-world environments.

PMID- 18720229
TI  - Increased arachidonic acid-induced thromboxane generation impairs skeletal muscle
      arteriolar dilation with genetic dyslipidemia.
AB  - OBJECTIVE: The aim of this study was to determine if arachidonic acid (AA)
      induced skeletal muscle arteriolar dilation is altered with hypercholesterolemia
      in ApoE and low-density lipoprotein receptor (LDLR) gene deletion mice fed a
      normal diet. This study also determined contributors to altered AA-induced
      dilation between dyslipidemic mice and controls, C57/Bl/6J (C57). METHODS:
      Gracilis muscle arterioles were isolated, with mechanical responses assessed
      following a challenge with AA under control conditions and after elements of AA
      metabolism pathways were inhibited. Conduit arteries from each strain were used
      to assess AA-induced production of PGI(2) and TxA(2). RESULTS: Arterioles from
      ApoE and LDLR exhibited a blunted dilation to AA versus C57. While responses were
      cyclo-oxygenase-dependent in all strains, inhibition of thromboxane synthase or
      blockade of PGH(2)/TxA(2) receptors improved dilation in ApoE and LDLR only. AA
      induced generation of PGI(2) was comparable across strains, although TxA(2)
      generation was increased in ApoE and LDLR. Arteriolar reactivity to PGI(2) and
      TxA(2) was comparable across strains. Treatment with TEMPOL improved dilation and
      reduced TxA(2) production with AA in ApoE and LDLR. CONCLUSIONS: These results
      suggest that AA-induced arteriolar dilation is constrained in ApoE and LDLR via
      an increased production of TxA(2). While partially due to elevated oxidant
      stress, additional mechanisms contribute that are independent of acute
      alterations in oxidant tone.

PMID- 18720232
TI  - Evidence of gender bias in legal insanity evaluations: a case vignette study of
      clinicians, judges and students.
AB  - Forensic psychiatric decision-making plays a key role in the legal process of
      homicide cases. Research show that women defendants have a higher likelihood of
      being declared legally insane and being diverted to hospital. This study
      attempted to explore if this gender difference is explained by biases in the
      forensic psychiatric assessments. Participants were 45 practicing forensic
      psychiatric clinicians, 46 chief judges and 80 psychology students. Participants
      received a written vignette describing a homicide case, with either a female or a
      male perpetrator. The results suggested strong gender effects on legal insanity
      judgements. Forensic psychiatric clinicians and psychology students assessed the
      case information as more indicative of legal insanity if the perpetrator was a
      woman than a man. Judges assessed offenders of their own gender, as they were
      more likely to be declared legally insane than a perpetrator of the opposite
      gender. Implications of and possible ways to minimize such gender biases in
      forensic psychiatric evaluations need to be thoroughly considered by the legal
      system.

PMID- 18720233
TI  - Comparative rates of freeze-drying for lactose and sucrose solutions as measured
      by photographic recording, product temperature, and heat flux transducer.
AB  - Sublimation from lactose and sucrose solutions has been monitored by temperature
      measurement, visual observation, heat flux sensing and manometric measurements.
      Estimates of energy transfer rates to the subliming mass made from visual
      observations and heat flux measurements are in broad agreement, demonstrating for
      the first time that heat flux sensors can be used to monitor the progress of
      lyophilization in individual vials with low sample volumes. Furthermore, it is
      shown that under identical lyophilization conditions the initial rate of drying
      for lactose solutions is low with little water sublimation for up to 150 minutes,
      which contrasts markedly with the much faster initial rate of drying for sucrose
      solutions. Measurement of the initial heat flux between shelf and vial indicated
      a lower flux to a 10% lactose solution than to a 10% sucrose solution.

PMID- 18720234
TI  - Preparation and characterization of salt forms of enalapril.
AB  - Selection of an optimal salt form of a drug candidate is a vital component of
      preformulation stage of drug development. In this study, six salts of enalapril-
      citrate, mesylate, tartrate, malate, besylate and tosylate--were prepared and
      characterized by Mass Spectroscopy, Differential Scanning Calorimetry,
      Thermogravimetric Analysis, Microscopy, Powder X-ray Diffraction, Karl Fischer
      Titration, High Performance Liquid Chromatography, Fourier-Transform Infra-red
      Spectroscopy and Head Space Gas Chromatography. All the six salts were subjected
      to a tiered screening involving five stages in the following order:
      crystallinity, hygroscopicity, solubility, stability and flow/compactability.
      Enalapril malate showed encouraging profile because of its lower hygroscopicity,
      higher solubility, good solid state stability, and better flow and
      compactability, in comparison to the marketed maleate salt.

PMID- 18720235
TI  - Formulations for intermittent release of parathyroid hormone (1-34) and local
      enhancement of osteoblast activities.
AB  - The objective of these studies was to develop simple, implantable devices that
      intermittently release PTH(1-34) and thus could be used for locally stimulating
      bone formation. The formulations were based on the association polymer system of
      cellulose acetate phthalate and Pluronic F-127. Release profiles for intermittent
      devices showed five discrete peaks, whereas sustained devices exhibited zero
      order kinetics. Osteoblastic activity was greater for cells intermittently
      treated with PTH(1-34) compared to sustained exposure. These controlled release
      devices delivering PTH(1-34) in an intermittent manner may be useful for
      affecting osteoblast activities in a localized area.

PMID- 18720236
TI  - Characterization and physical stability of spray dried solid dispersions of
      probucol and PVP-K30.
AB  - The main purpose of this study was to obtain stable, well-characterized solid
      dispersions (SDs) of amorphous probucol and polyvinylpyrrolidone K-30 (PVP-K30)
      with improved dissolution rates. A secondary aim was to investigate the flow
      through dissolution method for in-vitro dissolution measurements of small-sized
      amorphous powders dispersed in a hydrophilic polymer. SDs were prepared by spray
      drying solutions of probucol and different amounts of PVP-K30. The obtained SDs
      were characterized by dissolution rate measurements in a flow-through apparatus,
      X-ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC),
      Scanning Electron Microscopy (SEM), particle sizing (laser diffraction) and
      Brunauer-Emmett-Teller Method (BET) and results were compared with starting
      material and a physical mixture. The physical stability was monitored after
      storage at 25 degrees C and 60% RH for up to 12 weeks. The flow-through method
      was found suitable as dissolution method. All SDs showed improved in-vitro
      dissolution rates when compared to starting material and physical mixtures. The
      greatest improvement in the in-vitro dissolution rate was observed for the
      highest polymer to drug ratio. By means of the results from XRPD and DSC, it was
      argued that the presence of amorphous probucol improved the dissolution rate, but
      the amorphous state could not fully account for the difference in dissolution
      profiles between the SDs. It was suggested that the increase in surface area due
      to the reduction in particle size contributed to an increased dissolution rate as
      well as the presence of PVP-K30 by preventing aggregation and drug re
      crystallization and by improving wettability during dissolution. The stabilizing
      effect of the polymer was verified in the solid state, as all the SDs retained
      probucol in the amorphous state throughout the entire length of the stability
      study.

PMID- 18720237
TI  - Identification and control of a degradation product in Avapro film-coated tablet:
      low dose formulation.
AB  - A degradation product was formed during the long-term stability studies (LTSS) of
      the low dose formulation of Avapro film-coated tablet. The degradant was
      identified as the hydroxymethyl derivative (formaldehyde adduct) of the drug
      substance, irbesartan, based upon analysis with LC/MS, LC/MS/MS, and
      chromatographic comparison to the synthetic hydroxymethyl degradation product.
      Laboratory studies demonstrated that the interaction of individual excipients
      with the drug substance at elevated temperature and polyethylene glycol (PEG)
      used in the coating material, Opadry II White, leads to the generation of this
      formaldehyde adduct. Spiking of formaldehyde to the solution of drug substance
      gradually produced this impurity and the kinetics studies demonstrated that the
      reaction between formaldehyde and irbesartan is a second order reaction with a
      rate constant of 2.6 x 10(-4) M(-1)min(-1) at 25 degrees C in an aqueous media.
      The redevelopment of the formulation by eliminating PEG from the Opadry II White
      dry-blend system was enabled by understanding the formaldehyde adduct formation.

PMID- 18720238
TI  - Optimization of regression equation for prediction of viscosity of aqueous
      solutions of the cellulose derivatives.
AB  - Commercially, cellulose products are designated with viscosity grade measured at
      2% w/v concentration in water at 20 degrees C using an Ubbelohde viscometer. To
      represent viscosity/concentration curves, linear function of the eighth root of
      dynamic viscosity and the concentration is generally used. In this work, the
      influence on viscosity of aqueous solutions of methylcellulose 400 and
      hypromellose 4000 by temperature and polymer concentration was modelled using an
      empirically proposed multiple linear regression in which the transformation of
      viscosity by logarithm, the reciprocal value of the absolute temperature, and the
      concentration by square root was recommended. Due to this, the viscosity of both
      cellulose derivatives investigated could be predicted simultaneously with the
      mean difference between the observed data and the ones estimated equal to 16.2%.
      Expanding the linear regression with the linear interaction between logarithm of
      the polymer viscosity grade and square root of the polymer concentration, the
      precision of the viscosity prediction increased to the acceptable level of 4.1%.
      Other interactions between the studied variables did not provide significantly
      better results. The optimized regression equation enabled the prediction of
      kinematic, dynamic, relative, and specific viscosity of the aqueous solutions of
      cellulose derivatives. The dimensionless relative viscosity could be recommended
      because it takes into account the water viscosity at the same experimental
      temperature. Selecting viscosity grade of the cellulose derivative and
      temperature of measurement, the partial regression equations were obtained from
      which the relative viscosity could be determined as the function of the polymer
      concentration with the precision in range of 1.3-4.7%.

PMID- 18720239
TI  - Comparative evaluation of the binding properties of two species of Khaya gum
      polymer in a paracetamol tablet formulation.
AB  - A study was made of the comparative effects of polymers obtained from two species
      of khaya tree - Khaya senegalensis and Khaya grandifoliola - as binding agents in
      a paracetamol tablet formulation. The mechanical properties of the tablets were
      assessed using the tensile strength (T), brittle fracture index (BFI) and
      friability (F) of the tablets while the drug release properties of the tablets
      were assessed using disintegration and dissolution times. The tensile strength,
      disintegration and the dissolution times of tablets increased with the increase
      in binder concentration while F and BFI decreased. K. senegalensis gum produced
      tablets with stronger mechanical properties with less tendency to laminate, and
      longer disintegration and dissolution times than K. grandifoliola gum. The
      results suggest that the polymer gum from K. senegalensis will be more
      appropriate as a binding agent than the gum from K. grandifoliola when higher
      mechanical strength and slower release profiles of tablets are desired.

PMID- 18720240
TI  - Mechanoradical-induced degradation in a pharmaceutical blend during high-shear
      processing.
AB  - Mechanically generated radicals were shown to affect short-term stability of a
      model pharmaceutical formulation during high-shear processing. A formulation
      containing an oxidatively sensitive drug, either amorphous or crystalline, and a
      polymeric excipient was high-shear mixed and the resulting short-term degradation
      was determined with HPLC. High-shear mixing of the excipients was also carried
      out before drug addition to isolate effects on excipients versus those directly
      on the drug. Short-term drug stability was found to be strongly dependent on the
      amount of shear added to excipients prior to drug addition, regardless of
      morphology. A mechanism for the observed degradation based on mechanically
      generated radicals from microcrystalline cellulose is proposed. These results
      indicate that excipient high-shear exposure needs to be considered in regards to
      drug stability.

PMID- 18720241
TI  - A study on microwave-induced melt granulation in a single pot high shear
      processor.
AB  - Microwave-induced high shear melt granulation was compared with conventional melt
      granulation performed in the same processor. Admixtures of lactose 200M and
      anhydrous dicalcium phosphate were granulated with polyethylene glycol 3350.
      Different heating mechanisms in the two processes necessitated the use of
      different parameters for process monitoring and control. Mixer power consumption
      was suitable for monitoring agglomerate growth under microwave-induced heating.
      Product temperature was a better indicator of agglomeration propensity in
      conventional melt granulation. These were attributed to the disparities in heat
      acquisition rates and heating uniformities of the powders as well as variation in
      baseline mixer power consumption between the two processes.

PMID- 18720242
TI  - Mechanism of in vitro percutaneous absorption enhancement of carvedilol by
      penetration enhancers.
AB  - The effect of penetration enhancers like tulsi (basil) oil, eucalyptus oil, clove
      oil, black cumin oil, oleic acid and Tween 80 on the percutaneous absorption of
      model lipophilic drug-carvedilol was investigated using excised rat abdominal
      skin. Transdermal flux, permeability coefficient and enhancement factor were
      calculated for each penetration enhancer. Black cumin oil (5% v/v) was selected
      on the basis of its highest enhancement in permeation and was evaluated further
      for its mode of action using DSC, FTIR and histological studies. The results
      indicated that the oil shows its action by extraction of lipids from stratum
      corneum as well as by loosening the hydrogen bonds between ceramides subsequently
      leading to fluidization of the lipid bilayer.

PMID- 18720243
TI  - Preparation of polymeric and ceramic porous capsules by a novel
      electrohydrodynamic process.
AB  - The preparation of capsules for medical and industrial use can be achieved via
      several conventional routes, yielding either hard or soft receptacles, depending
      on the type and the content of the material to be encapsulated. Together with
      tablets, capsules are amongst the most commonly used means of administering
      medication and this makes progress in capsule preparation technology a key area
      of drug delivery research. Here we uncover new technology for the preparation of
      capsules with porous chambers. The novelty is signified in the use of an
      electrohydrodynamic process engineering route and its potential is elucidated
      using a polymeric material; polymethylsilsesquioxane, which can be converted into
      an identical ceramic form by means of simple pyrolysis. Thus, both polymeric and
      ceramic capsules have been prepared. The effects of process control parameters
      such as the applied voltage and flow rate, on the characteristics of the capsules
      prepared are discussed.

PMID- 18720244
TI  - Chitosan ascorbate: a chitosan salt with improved penetration enhancement
      properties.
AB  - The aim of the present work was to investigate if chitosan salification with
      ascorbic acid could produce an increase in chitosan penetration enhancement
      properties towards buccal mucosa and intestinal Caco-2 cell monolayer. Three
      different chitosan grades were considered. Chitosan hydrochloride and lactate
      were used as references. Fluorescein isothiocyanate-dextran (FD4), a hydrophilic
      high MW molecule, was employed as model penetrant. Chitosan ascorbate showed
      better penetration enhancement properties towards both buccal porcine mucosa and
      Caco-2 cell monolayer with respect to hydrochloride and lactate salts.
      Cytotoxicity of chitosan ascorbate assessed on Caco-2 cells was comparable with
      those of chitosan hydrochloride and lactate.

PMID- 18720245
TI  - A comparative histological study of alginate beads as a promising controlled
      release delivery for mefenamic acid.
AB  - The new mefenamic acid-alginate bead formulation prepared by ionotropic gelation
      method using 3 x 2(2) factorial design has shown adequate controlled release
      properties in vitro. In the present study, the irritation effects of mefenamic
      acid (MA), a prominent non-steroidal anti-inflammatory (NSAI) drug, were
      evaluated on rat gastric and duodenal mucosa when suspended in 0.5% (w/v)
      sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads.
      Wistar albino rats weighing 200 +/- 50 g were used during in vivo animal studies.
      In this work, biodegradable controlled release MA beads and free MA were
      evaluated according to the degree of gastric or duodenal damage following oral
      administration in rats. The gastric and duodenal mucosa was examined for any
      haemorrhagic changes. Formulation code A10 showing both Case II transport and
      zero order drug release and t(50) % value of 5.22 h was chosen for in vivo animal
      studies. For in vivo trials, free MA (100 mgkg(-1)), blank and MA (100 mgkg(-1))
      loaded alginate beads (formulation code A10) were suspended in 0.5% (w/v) NaCMC
      solution and each group was given to six rats orally by gavage. NaCMC solution
      was used as a control in experimental studies. In vivo data showed that the
      administration of MA in alginate beads prevented the gastric lesions.

PMID- 18720246
TI  - Preparation and evaluation of piroxicam-HPMCAS solid dispersions for ocular use.
AB  - The aim of the study was in vitro evaluation of piroxicam solid dispersions
      containing hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF, -HF) as a
      carrier. Binary (piroxicam-HPMCAS) and ternary (piroxicam-HPMCAS-Carbopol 940)
      solid dispersions were prepared by spray-drying method. The morphological
      characteristics were investigated by scanning electron microscopy. X-ray
      diffraction and differential scanning calorimetry were employed to study physical
      and chemical properties. In vitro release was studied using a flow-through cell
      technique. Studies of dissolution rate of piroxicam from solid dispersions were
      carried out in comparison with corresponding physical mixtures and drug alone.
      The dissolution profiles depend on the presence of Carbopol 940 in solid
      dispersions.

PMID- 18720247
TI  - Moisturizing effect of oleogel/hydrogel mixtures.
AB  - The aim of this study was to obtain new vehicles for topical formulations based
      on the mixture of hydrogels (aqueous systems) with oleogels (lipophilic systems).
      Several formulations were prepared using different oleogels mixed with
      polyacrylic acid hydrogel without addition of other ingredients. The moisturizing
      effect of the bigels was assessed along with the hydrogel and oleogels used in
      their preparation by carrying out an in vivo study with 14 healthy volunteers.
      Corneometer measurements were taken each hour during a five-hour period after
      product's application. Stability tests (storage at 20 and 40 degrees C for six
      months) and mechanical characterization were also carried out. Stability tests
      showed no modifications of the textural properties and appearance over a six
      month period at 20 degrees C. At accelerated conditions, modifications of colour
      and textural properties were detected after six months' storage. While retaining
      the mechanical and sensory properties of the hydrogel, the bigels showed
      simultaneously an enhanced moisturizing effect, making them promising candidates
      for topical formulations.

PMID- 18720248
TI  - Controlled release solid dosage forms using combinations of (meth)acrylate
      copolymers.
AB  - Controlled release solid oral dosage forms have been widely used for decades,
      enabling drugs to be administered more comfortably while at the same time
      providing a sustained and reproducible method of release. (Meth)acrylate
      copolymers are one of the options available when considering a sustained release
      solid form. Due to their different functionalities it is possible to achieve
      various different release profiles. The electrical character of these copolymers
      and their pH-dependent solubility can result in new and modified patterns when
      these polymers are combined. This review sheds light on various studies involving
      combinations of (meth)acrylate copolymers for use in multi-unit systems and
      matrix tablets, and also on several analytical methods that help to identify
      possible interactions between these polymers.

PMID- 18720249
TI  - Spherical crystallization of mebendazole to improve processability.
AB  - Spherical crystallization technique combines crystallization and agglomeration
      directly to generate spherical crystals with improved micromeretic properties,
      thus obviating need for further processing by granulation and agglomeration. The
      present study was focused on spherical crystallization of an antihelmentic drug -
      Mebendazole (MBZ) - using spherical agglomeration technique. Apart from being
      poorly water-soluble, MBZ exhibits poor flow and compressibility owing to its
      needle shaped crystal habit and electrostatic charge. Spherical agglomeration was
      carried out in the presence of different bridging liquids (hexane, octanol,
      toluene, dichloromethane) and polymers (polyethylene glycol, cross-povidone,
      starch, cross carmellose sodium, hydroxyl propyl methyl cellulose (HPMC),
      hydroxyl propyl cellulose (HPC), ethyl cellulose (EC), Eudragit S100, Eudragit
      RLPO, Eudragit RD100, Eudragit E), by employing different crystallization
      conditions such as variation of polymer type, polymer concentration, and rate of
      stirring. The final parameters were optimized to obtain crystals with an aspect
      ratio in the range of 1-2 compared to a value of 12 for untreated MBZ. These
      agglomerates retained form C of MBZ, and exhibited good flow properties, high
      bulk density and improved compressibility. Lower elastic:plastic energy (EE/PE)
      ratio for spherical crystals generated in the presence of Eudragit-S100 and
      Hydroxypropylcellulose (HPC) indicated better compressibilty of spherical
      crystals.

PMID- 18720250
TI  - Controlled release of DSBP from genipin-crosslinked gelatin thin films.
AB  - Controlled release of a marker drug, 4,4'-bis(2-sulfostyryl) biphenyl (DSBP) from
      genipin crosslinked gelatin thin films, with application to drug delivery by
      transdermal patches is studied in this paper. A simple method for fabrication of
      nano-thin films, using basic lab equipment is introduced. This method consists of
      two steps: dipping of the substrate in a deposition solution, followed by
      centrifugation of the substrate. Also, swelling and drug release from thin films
      is modeled, using the Fick's second law of diffusion. The effect of genipin
      concentration on release of DSBP molecules from thin films is investigated,
      experimentally and numerically. The results show that controlled release of DSBP
      from the genipin-crosslinked gelatin thin films is achieved, using various
      concentrations of genipin in gelatin.

PMID- 18720251
TI  - In vitro evaluation of theophylline matrices using xyloglucan.
AB  - Xyloglucan is a water soluble polysaccharide extracted from the beans of
      Tamarindus Indica. Very few publications are found related to its use for
      preparing oral sustained release swellable matrix. The purpose of this
      investigation was to prepare sustained release matrices using Xyloglucan and
      investigate the effects of polymer level, diluents type, pH and ionic strength of
      the dissolution medium, basket rotational speed, and swelling isotherms on drug
      release. Tablet formulations containing 50% theophylline as a drug model,
      Xyloglucan cold water soluble (20%, 30 and 40%) and different diluents (Avicel PH
      101, lactose and dibasic calcium phosphate) were prepared. The formulation
      containing 30% Xyloglucan water soluble and Avicel was selected as best
      formulation because it gives controlled release profile and tested for swelling
      isotherms, drug release in different dissolution media, and different basket
      rotational speed. Percent drug release from formulations containing 50%
      theophylline, 30% Xyloglucan water soluble, and Avicel PH-101 was 34.2% at 6
      hours, 35.6% with lactose, and 30.9% with Emcompress. ANOVA two-way analysis
      showed a change in drug release rate when polymer percent was increased at the 5%
      significance level. Different diluents, different dissolution media, and
      different basket rotational speeds did not significantly change the drug release.
      The mechanism of drug release appears to follow anomalous relaxation for
      swellable matrix.

PMID- 18720252
TI  - The challenges of upgrading from ISPO Category II level to Bachelor Degree level
      by distance education.
AB  - The Cambodian School of Prosthetics and Orthotics (CSPO) in collaboration with La
      Trobe University, Australia, has established an upgrade programme from ISPO
      Category II level to a Bachelor Degree in Prosthetics and Orthotics. One group of
      students have completed the course and following a review process, a second group
      are now enrolled. The upgrade curriculum focuses on clinical reasoning and
      development of learning skills. A survey aimed to investigate the challenges of
      the programme using long distance education was prepared and data was gathered by
      questionnaires delivered to the organizer, host, coordinators, lecturers and
      students of the programme. Eleven subjects from various backgrounds participated
      in the questionnaire. The questionnaire showed the programme improves the
      capacity of the clinicians and future educators in Cambodia and the region. The
      distance education course delivery method was found to be beneficial for the
      students and allows them to remain in their home country. In addition, there is a
      cost reduction compared to full-time study in Australia.

PMID- 18720253
TI  - Delayed diagnosis of atypical mycobacterial skin and soft tissue infections in
      non-immunocompromized hosts.
AB  - Relapsing or persisting skin and soft tissue infections after injury with
      biological materials should prompt consideration of atypical mycobacteria, even
      in non-immunocompromized hosts. We report 3 cases where diagnosis was delayed for
      3-10 months. Insidiously, Mycobacterium marinum infection can occur without any
      contact to fish tank or swimming pool.

PMID- 18720254
TI  - Neuroborreliosis recurrence: reinfection or relapse?
AB  - We report the case of a 47-y-old female with documented neuroborreliosis, who had
      a complete recovery after 10 d of intravenous high-dose penicillin followed after
      9 months by a new episode of documented neuroborreliosis. The case probably
      represents a rare case of true reinfection rather than relapse.

PMID- 18720255
TI  - Actinobacillus (Aggregatibacter) actinomycetemcomitans (HACEK) identified by
      PCR/16S rRNA sequence analysis from the heart valve in a patient with blood
      culture negative endocarditis.
AB  - We report a case of infective endocarditis caused by Actinobacillus
      actinomycetemcomitans (Aggregatibacter actinomycetemcomitans) from the HACEK
      group diagnosed by PCR/16S from the heart valve. Multiple blood cultures and
      cultures from heart valve were negative and cardiac surgery was performed due to
      therapeutic and cardiac failures. Molecular biological methods are useful in such
      a patient, to choose an optimal antibiotic treatment post-surgery.

PMID- 18720256
TI  - Surveillance of bacterial meningitis in children under 2 y of age in Denmark,
      1997-2006.
AB  - Worldwide the 3 most common pathogens for bacterial meningitis among infants and
      young children are Haemophilus influenzae, Streptococcus pneumoniae and Neisseria
      meningitidis. Denmark included in the National Childhood Vaccination Programme
      vaccination against H. influenzae type B (Hib) in 1993 and invasive pneumococcal
      disease as of October 2007. Introduction of the conjugated heptavalent
      pneumococcal vaccine is, as in the post-Hib vaccination era, expected to change
      the epidemiology of bacterial meningitis in infants and young children. In 1980
      it became mandatory to report suspected cases of bacterial meningitis and the
      surveillance system was further enhanced for laboratory diagnosed cases of N.
      meningitis in 1992 and S. pneumoniae in 1996 when a reminder procedure to the
      physician was issued. In this article we review the epidemiology of 418 notified
      cases of bacterial meningitis in children <2 y of age in Denmark in the pre
      pneumococcal vaccination era 1997-2006 and discuss points of awareness for the
      future surveillance system.

PMID- 18720258
TI  - Antimicrobial therapy and shedding time of Shiga toxin-producing Escherichia
      coli.

PMID- 18720259
TI  - Epidemiological investigation of a varicella outbreak in an Italian prison.
AB  - Five cases of varicella occurred in a women's prison in Rome. A serosurvey
      conducted in the prison found that 14.5% of the inmates were susceptible. The
      sensitivity and positive predictive value of a history of varicella were high,
      whereas specificity was rather low. The attack rate among susceptible inmates was
      approximately 22%. Preventive measures probably contributed to reduce infection
      spread.

PMID- 18720260
TI  - Congenital CMV infection: prevalence in newborns and the impact on hearing
      deficit.
AB  - Congenital cytomegalovirus (CMV) infection is asymptomatic in 90% of infected
      newborns but approximately 10-20% of these infants are at risk of developing
      sequelae later, mostly hearing deficit. The aims of the study were to investigate
      the prevalence of congenital CMV infection in a Swedish population of newborns
      and investigate the relative risk of hearing deficit in newborns with congenital
      CMV infection. The dried blood spot (DBS) samples of 6060 newborns in southern
      Stockholm during 12 months (October 2003-June 2004; August 2004-October 2004)
      were analysed for CMV DNA by TaqMan based real-time PCR. Hearing deficit was
      assessed by otoacoustic emission (OAE) within a newborn screening programme. 12
      infants out of 6060 or 0.2% (95% CI 0.1-0.3%) had congenital CMV infection. One
      boy among the 12 infected infants had unilateral hearing loss, indicating that
      the risk of hearing loss is greatly increased (about 20 times) in CMV infected
      infants. No child developed ocular complications such as chorioretinopathy during
      3 y of follow-up. Congenital CMV has an impact on child health but can easily be
      overlooked due to lack of signs in the neonatal period. Surveillance for
      congenital CMV is important in addition to programmes for prevention and
      treatment.

PMID- 18720261
TI  - Swedish guidelines for diagnosis and treatment of infective endocarditis
      recommend overuse of transoesophageal echocardiography.
AB  - Echocardiography has a vital role for diagnosing and monitoring infectious
      endocarditis. The recently published Swedish guidelines for diagnosis and
      treatment of infectious endocarditis recommend overuse of transoesophageal
      echocardiography, which is not supported by the literature. The European Society
      of Cardiology presents a considerably more appropriate opinion.

PMID- 18720262
TI  - High mobility group box 1 (HMGB1) and macrophage migration inhibitory factor
      (MIF) in Kawasaki disease.
AB  - OBJECTIVE: To investigate whether two proinflammatory cytokines, high mobility
      group box 1 (HMGB1) and macrophage migration inhibitory factor (MIF) are involved
      in the development of Kawasaki disease (KD). METHODS: Twenty-seven patients with
      KD were included in this study. Eleven patients with sepsis and 28 healthy
      children served as controls. Serum levels of HMGB1 and MIF were measured by
      corresponding enzyme-linked immunosorbent assay (ELISA) kits, respectively. Real
      time polymerase chain reaction (PCR) was used to quantify the expression levels
      of genes encoding receptor for advanced glycation end-products (RAGE), an HMGB1
      receptor, and CD74, an MIF receptor in peripheral blood mononuclear cells
      (PBMCs). RESULTS: Serum levels of HMGB1 and MIF in KD patients were the highest
      in the early acute phase and gradually decreased after defervescence. Serum HMGB1
      and MIF levels in KD patients were significantly higher than those in controls
      (HMGB1, p<0.001; MIF, p<0.01). The expression levels of the RAGE gene and CD74
      gene in KD patients were significantly higher than those in controls (RAGE,
      p<0.001; CD74, p<0.01). CONCLUSION: These data suggest that HMGB1 and MIF play an
      important role in immune responses in KD patients.

PMID- 18720263
TI  - Upregulation of 78-kDa glucose-regulated protein in macrophages in peripheral
      joints of active ankylosing spondylitis.
AB  - OBJECTIVES: To investigate the expression of the 78-kDa glucose-regulated protein
      (GRP78), a marker of activation of the unfolded protein response (UPR), in
      macrophages of ankylosing spondylitis (AS) synovium and synovial fluid and to
      explore the relationship between the expression of GRP78 and synovial fluid
      levels of the proinflammatory cytokines, as well as the inflammatory activity of
      AS. METHODS: Immunohistochemical staining and Western blotting were performed to
      detect the expression of GRP78 in macrophages in the involved peripheral joints
      of 16 patients with active AS, and in 15 patients with osteoarthritis (OA) as
      controls. Synovial fluid levels of tumour necrosis factor-alpha (TNFalpha) and
      interleukin-6 (IL-6) of AS peripheral joints were measured using an enzyme-linked
      immunosorbent assay (ELISA). The inflammatory activity of AS was measured by the
      sera levels of IL-6 and the Bath Ankylosing Spondylitis Disease Activity Index
      (BASDAI). RESULTS: Expression of GRP78 in macrophages was increased significantly
      in the affected peripheral joints of AS compared with OA patients. Positive
      correlations were found between the expression of GRP78 in macrophages in AS
      affected peripheral joints and the synovial fluid levels of TNFalpha and IL-6, as
      well as the sera levels of IL-6 and the BASDAI. CONCLUSIONS: Activation of the
      UPR occurs in macrophages in both the synovium and synovial fluids of AS-involved
      peripheral joints, and there may be a link between activation of the UPR of
      macrophages and local production of the proinflammatory cytokines, as well as the
      inflammatory activity of AS.

PMID- 18720264
TI  - Multiple sclerosis following etanercept treatment for ankylosing spondylitis.

PMID- 18720265
TI  - A patient with periodic fever syndrome: a 20-year delay in diagnosis.

PMID- 18720266
TI  - Project Towards No Drug Abuse (TND): needs assessment of a social service
      referral telephone program for high risk youth.
AB  - The purpose of this study was to conduct a needs assessment of a potential social
      service resource telephone program component among high risk youth who received
      the Project Towards No Drug Abuse (TND) classroom-based program (approximately 1
      year earlier). Results supported youths' overwhelming receptiveness of a social
      service referral program. The vast majority of respondents indicated a strong
      desire for resource and referral information on vocational, educational,
      recreational, transportation, and mental health and drug counseling. Further
      research is needed to investigate the effectiveness of the provision of social
      service resource information on drug use among emerging adults.

PMID- 18720267
TI  - Neuropsychological functioning of opiate-dependent patients: a nonrandomized
      comparison of patients preferring either buprenorphine or methadone maintenance
      treatment.
AB  - OBJECTIVES: In the present study, we investigated whether buprenorphine as a
      partial mu-opioid receptor agonist is associated with less cognitive impairment
      than methadone. METHODS: Neuropsychological functioning of opioid-dependent
      patients, previously assigned to methadone (MMP, n = 30) or buprenorphine (BMP, n
      = 26) maintenance treatment according to their own preference, was compared and
      dose effects were investigated. RESULTS: MMP and BMP performed equally well on
      all measures of neuropsychological functioning including the trail making test,
      the continuous performance test, and a vigilance task. However, patients
      receiving a higher dose of methadone were impaired in a vigilance task.
      CONCLUSIONS: In a free-choice administration of methadone or buprenorphine, there
      seems to be no difference in cognitive functioning. Possible explanations are
      discussed.

PMID- 18720268
TI  - Disrupted white matter integrity in heroin dependence: a controlled study
      utilizing diffusion tensor imaging.
AB  - OBJECTIVES: Fractional anisotropy (FA) via diffusion tensor imaging (DTI) can
      quantify the white matter integrity. Exposure to addictive drugs, such as
      alcohol, cocaine, methamphetamine, marijuana, and nicotine has been shown to
      alter FA. White matter abnormalities have been shown, but it remains unclear
      whether the white matter FA is altered in heroin dependence. METHODS: Utilizing
      DTI, we investigated the FA difference between heroin-dependent and control
      subjects by a voxel-based strategy. The FA values of the identified regions were
      calculated from the FA image of each subject and were correlated with clinical
      features including months of heroin use, age, education, and dose of methadone.
      RESULTS: Reduced FA among 16 heroin dependent subjects was located in the
      bilateral frontal sub-gyral regions, right precentral and left cingulate gyrus.
      FA in the right frontal sub-gyral was negatively correlated with duration of
      heroin use. CONCLUSION: The disrupted white matter integrity in right frontal
      white matter may occur in continuous heroin abuse.

PMID- 18720269
TI  - Insight into alcohol-related problems and its associations with severity of
      alcohol consumption, mental health status, race, and level of acculturation in
      southern Taiwanese indigenous people with alcoholism.
AB  - OBJECTIVE: While not well known in the West, Taiwan has a substantial indigenous
      population, and this population has rapidly developed alcohol problems. This
      study examined the level of insight into alcohol-related problems and its
      associations with the severity of alcohol consumption, mental health status,
      race, and the level of acculturation among indigenous populations with alcohol
      problems in southern Taiwan. METHODS: A total of 332 indigenes, whose total
      Alcohol Use Disorders Identification Test (AUDIT) score was equal to 8 or higher,
      were interviewed. The associations between the level of insight into alcohol
      related problems and the severity of alcohol drinking on the AUDIT, mental health
      status on the Chinese Health Questionnaire-12 (>or= 4 vs. < 4), race (Bunun vs.
      non-Bunun), and the level of acculturation on the Taiwan Aboriginal Acculturation
      Scale were examined using logistic regression models. RESULTS: The results of
      this study found that 72.6% of the participants had poor insight into alcohol
      related problems and no participant had good insight. Participants who had more
      severe alcohol drinking or poor mental health were more likely to have a higher
      level of insight into alcohol-related problems. Participants who were non-Bunun
      were also more likely to have a higher level of insight into alcohol-related
      problems, but the level of acculturation was not associated with the level of
      insight into alcohol-related problems. CONCLUSIONS: These findings suggest that
      most alcoholic indigenes in southern Taiwan have poor insight into their own
      alcohol-related problems. Cultural specific interventions targeting and improving
      the indigenes' insight into alcohol-related problems are needed.

PMID- 18720270
TI  - Trends in alcohol- and drug-related ED and primary care visits: data from three
      US National Surveys (1995-2005).
AB  - OBJECTIVE: To evaluate trends in alcohol- and drug-related emergency department
      (ED) and primary care visits over the previous decade. METHOD: A trend analysis
      was conducted on substance-related health services visit data, based on self
      reported drinking or drug use within six hours prior to an injury or illness
      event, from the 1995, 2000, and 2005 National Alcohol Surveys. RESULTS: Although
      an upward trend was observed in alcohol-related ED visits from 1995 to 2005, this
      increase was not significant. A significant trend was found for drug-related ED
      visits from .6% in 1995 to 3.7% in 2005 (p < .01). In multiple logistic
      regression, year of survey (2000 vs. 1995) was positively predictive of drug
      related ED visits, controlling for gender, age, ethnicity, and health insurance
      coverage; however, year of survey (2005 vs. 2000) was not significant.
      CONCLUSION: These data suggest that drug-related ED visits are continuing to
      increase, although the increase has not been as substantial between 2000 and 2005
      as that which was observed between 1995 and 2000 and highlight the opportunity
      provided by the ED and primary care settings for screening and brief intervention
      for substance-related problems. These findings also suggest that Healthy People
      2010 objectives calling for a reduction in substance-related visits may not be
      reached.

PMID- 18720271
TI  - Predictors of life satisfaction among caregivers of individuals with multiple
      sclerosis.
AB  - Research on life satisfaction among caregivers of persons with multiple sclerosis
      (MS) is sparse. This study examined the extent to which MS-specific disease and
      psychosocial characteristics predict caregiver life satisfaction. Participants
      were 64 caregivers of patients with MS and the patients for whom they care.
      Multiple regression analysis indicated that caregiver perception of illness
      uncertainty and patients' unawareness of deficits have unique value in predicting
      caregiver life satisfaction, even after accounting for general financial status.
      Gender and level of social support were also important contributing factors to
      caregiver life satisfaction. The findings suggest that duration and severity of
      the patients' illness take a greater toll on life satisfaction of caregivers with
      low versus high social support, particularly among women caregivers.

PMID- 18720272
TI  - The prediction of change: normative neuropsychological trajectories.
AB  - While the application of normative standards is vital to the practice of clinical
      neuropsychology, data regarding normative change remains scarce despite the
      frequency of serial assessments. Based on 285 normal individuals, we provide co
      normed baseline data with demographic adjustments and test-retest standardized
      regression based (SRB) models for three time points for several measures. These
      models delineate normal, expected change across time, and yield standardized z
      scores that are comparable across tests. Using a new approach, performance on any
      previous trial was accounted for in the subsequent models of change, yielding
      serial normative formulas that model change trajectories rather than simple
      change from point to point. These equations provide indices of deviation from
      expected baseline and change for use in clinical or research settings.

PMID- 18720273
TI  - The accuracy of general practitioners' clinical assessment of chest pain
      patients.
AB  - OBJECTIVE: To study general practitioners' (GP) assessment of the probability of
      ischaemic heart disease (IHD) and GP action in daily practice regarding chest
      pain patients. METHODS: All chest pain patients aged 20-79 years, attending three
      primary health-care centres in south-east Sweden and assessed by the GP to have
      high, low or very low probability of IHD, were included consecutively over a two
      year period. The "GP action in daily practice" was classed as "active decisions"
      (investigation or treatment) or "wait and see". "IHD" or "not IHD" was settled
      according to the results of acute hospital investigation or exercise
      testing/myocardial perfusion scintigraphy. RESULTS: 516 patients were included,
      93 high, 145 low and 278 very low probability cases. The outcome was "IHD" in
      47%, 9% and 1% respectively. The sensitivity and specificity of the "GP
      assessment of the probability of IHD" were 72% and 89%. The sensitivity and
      specificity of the "GP action in daily practice" were 88% and 72%, respectively.
      The negative predictive value was 98%. CONCLUSION: GP assessment, after clinical
      evaluation, that the probability of IHD was low did not safely rule out IHD. GP
      action in daily practice however, indicates that general practice is an
      appropriate level of care for chest pain patients.

PMID- 18720274
TI  - Coronary heart disease and cardiovascular risk factors among people aged 25-65
      years, as seen in Romanian primary healthcare.
AB  - BACKGROUND: In Romania data on cardiovascular risk factors are sparse. OBJECTIVE:
      To describe the prevalence and distribution of cardiovascular risk factors in a
      primary care setting in Romania. METHODS: In a cross-sectional study, patients
      aged 25-65 years on the lists of four general practitioners in Iasi (Romania),
      selected by 1/5 systematic sampling, were invited for a cardiovascular risk
      evaluation (interview, physical examination, blood tests for cholesterol and
      glucose). Prevalence rates for coronary heart disease (CHD), diabetes (DM) and
      other risk factors were estimated, SCORE risk was determined, and treatment
      targets were evaluated. RESULTS: The response rate was 79% (325 men, 476 women).
      Prevalence rates were: CHD 7.4%, DM 3.2%, hypercholesterolemia (>190 mg%) 47.2%,
      hypertension 23.7%, obesity 21.2%, and smoking 33.8%. In women, obesity and lack
      of physical exercise were more prevalent, whereas in men, higher rates were found
      for smoking and an unhealthy diet. The proportion of patients considered to be at
      high risk (CHD, DM or SCORE >or= 5%) was 39.2%. Female patients failed to meet
      targets for systolic blood pressure, total cholesterol and glucose, whereas
      smoking cessation will be the greatest challenge for men. CONCLUSION: There were
      relevant gender differences in modifiable cardiovascular risk factors. Many
      patients failed to meet treatment targets.

PMID- 18720275
TI  - Superior discrimination between similar stimuli after simultaneous exposure.
AB  - Human participants received unsupervised exposure to difficult-to-discriminate
      chequerboard stimuli (e.g., AX and BX), before learning a discrimination between
      them. Experiment 1 demonstrated that prior exposure enhanced later discrimination
      and that intermixed exposure (AX, BX, AX, BX ...) resulted in better subsequent
      discrimination than did blocked exposure (CY, CY ... DY, DY ...). Experiment 2
      showed that simultaneous exposure to two similar stimuli (AX-BX, BX-AX ...)
      facilitated the later acquisition of a successive discrimination, more than
      successive exposure (AX-AX, BX-BX ...). These results parallel those observed by
      Mundy, Honey, and Dwyer (2007) who used pictures of human faces as stimuli and
      establish the generality of the fact that simultaneous exposure produces a
      particularly marked perceptual learning effect.

PMID- 18720276
TI  - Colour versus quantity as cues in reverse-reward-competent squirrel monkeys
      (Saimiri sciureus).
AB  - To assess the relative salience of colour and quantity cues, squirrel monkeys
      previously trained to reach for the smaller of two quantities of food in a
      reverse-reward contingency task received colour discrimination training. After
      initial failure to discriminate between two colours of dots under a differential
      reinforcement regime, they learned the task when the S- colour was associated
      with zero reward. The monkeys then showed good retention on the original reverse
      reward task of 1 versus 4 with pairs of dots presented in S+ or S- colours.
      However, on "mismatch" trials of 1S- versus 4S+ , only 2 of 4 monkeys tested
      showed a preference--1 monkey chose based on quantity, the other based on colour.
      Individual differences and the possible roles of overshadowing and blocking are
      discussed.

PMID- 18720277
TI  - Processing ambiguous Spanish se in a minimal chain.
AB  - The recovery of pieces of information that are not linguistically expressed is a
      constant feature of the process of language comprehension. In the processing
      literature, such missing information is generally referred to as "gaps". Usually,
      one resolves gaps by finding "fillers" in either the sentence or the context. For
      instance, in Peter seemed to be upset, Peter is really the subject of being upset
      but appears as surface subject of seems. Sometimes constituents move, leaving
      gaps behind. Various Romance languages such as Spanish or Italian have a
      grammatical particle se/si, which, as it is extremely ambiguous, licenses
      different sorts of gaps. In Spanish, se can encode at least reflexive,
      impersonal, and passive meanings. In an eye-tracking experiment we contrast
      reflexive structures containing postverbal subjects with impersonal structures
      with no subjects (GAP se vendo apresuradamente el corredor/"the runner bandaged
      himself hurriedly" vs. GAP se vendo apresuradamente al corridor/"(someone)
      bandaged the runner hurriedly"). In a second manipulation we contrast the
      presence of an extra argument with se-passives (GAP se vendo el tobillo el
      corredor/"the runner bandaged his ankle" vs. GAP se vendo el tobillo al
      corridor/"the runner's ankle was bandaged"). Our comparisons involve contrasting
      standard transitive structures with nonstandard word order (postverbal subject
      and a preverbal subject gap) against inherently complex and less habitual
      structures such as impersonals (with no subject) or se-passives (with subjects in
      canonical object position). We evaluate the minimal chain principle (de Vincenzi,
      1991), according to which displacement is costly because it entails complex
      (derivational) "chains" that must be undone before phrasal packaging can
      commence. We show the minimal chain principle to be essentially correct when
      contrasting more complex but more frequent structures with less complex but less
      frequent structures. A noteworthy feature of this research is that the gaps
      appear before the fillers in the structures that we analyse.

PMID- 18720278
TI  - Recognition accuracy for original and altered verbal memory reports in older
      adults.
AB  - The current study examined four factors that were expected to influence
      recognition accuracy of previously retrieved events: remoteness of the event,
      rated emotionality of the event, the type of changes that were made to the
      original memory report, and the plausibility of these changes. This was done in a
      study with 33 participants who were tested for recognition accuracy of original
      and altered reports a year after they had initially reported these
      autobiographical memories. Participants evaluated original and altered reports as
      being authentic or not. High recognition accuracy occurred for report evaluations
      of events that were recent, that contained central changes, and that had higher
      emotional intensity ratings. Recognition errors were more likely to occur when
      the original events were remote and when altered reports contained peripheral and
      plausible changes. These findings demonstrate the vulnerability of recognition
      accuracy in older adults under difficult retrieval conditions.

PMID- 18720279
TI  - Assessing the automaticity of moral processing: efficient coding of moral
      information during narrative comprehension.
AB  - A long-standing theoretical debate concerns the involvement of principled
      reasoning versus relatively automatic intuitive-emotional processing in moral
      cognition. To address this, we investigated whether the mental models formed
      during story comprehension contain a moral dimension and whether this process is
      affected by cognitive load. A total of 72 participants read stories about
      fictional characters in a range of moral situations, such as a husband being
      tempted to commit adultery. Each story concluded with a "moral" or "immoral"
      target sentence. Consistent with a framework of efficient extraction of moral
      information, participants took significantly longer to read immoral than moral
      target sentences. Moreover, the magnitude of this effect was not compromised by
      cognitive load. Our findings provide evidence of efficient coding of moral
      dimensions during narrative comprehension and demonstrate that this process does
      not require cognitively intense forms of principled reasoning.

PMID- 18720280
TI  - Self-construal priming modulates the scope of visual attention.
AB  - Although it is well documented that cultures influence basic cognitive processes
      such as attention, the underlying mechanisms remain unclear. We tested the
      hypothesis that self-concepts that characterize people from different cultures
      mediate the variation of visual attention. After being primed with self
      construals that emphasize the Eastern interdependent self or the Western
      independent self, Chinese participants were asked to discriminate a central
      target letter flanked by compatible or incompatible stimuli (Experiment 1) or
      global/local letters in a compound stimulus (Experiment 2). Experiment 1 showed
      that, while responses were slower to the incompatible than to the compatible
      stimuli, this flanker compatibility effect was increased by the interdependent
      relative to the independent self-construal priming. Experiment 2 showed that the
      interdependent-self priming resulted in faster responses to the global than to
      the local targets in compound letters whereas a reverse pattern was observed in
      the independent-self priming condition. The results provide evidence for dynamics
      of the scope of visual attention as a function of self-construal priming that
      switches self-concept toward the interdependent or independent styles in Chinese.

PMID- 18720281
TI  - Why do we slow down after an error? Mechanisms underlying the effects of
      posterror slowing.
AB  - People often become slower in their performance after committing an error, which
      is usually explained by strategic control adjustments towards a more conservative
      response threshold. The present study tested an alternative hypothesis for
      explaining posterror slowing in terms of behavioural interferences resulting from
      error monitoring by manipulating stimulus contrast and categorization difficulty
      in a choice reaction time task. The response-stimulus interval (RSI) was either
      short or long, using a between-subject (Experiment 1) and a within-subject design
      (Experiment 2). Posterror slowing was larger and posterror accuracy lower in
      short than in long RSI situations. Effects of stimulus contrast disappeared in
      posterror trials when RSI was short. At long RSIs, stimulus contrast was additive
      with posterror slowing. The results support the idea that at least two mechanisms
      contribute to posterror slowing: a capacity-limited error-monitoring process with
      the strongest influence at short RSIs and a criterion adjustment mechanism at
      longer RSIs.

PMID- 18720282
TI  - Strategies to prevent N-acetyltransferase-mediated metabolism in a series of
      piperazine-containing pyrazalopyrimidine compounds.
AB  - 1. (1-Methyl-5-piperazine-1-yl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-(5
      methyl-pyridin-2-yl)-amine (UK-469,413) was identified as a lead compound in a
      new medicinal chemistry programme. UK-469,413 had good physicochemical properties
      and was slowly metabolized by cytochromes P450 in rat and human liver microsomes.
      2. In the rat in vivo the compound was rapidly cleared. Subsequent studies showed
      that UK-469,413 was rapidly acetylated in rat liver cytosol to an N
      acetylpiperazine metabolite that was the major circulating metabolite in rat
      plasma in vivo. 3. Analogues of UK-469,413 containing the unsubstituted
      piperazine moiety were rapidly acetylated in rat liver cytosol and had high
      plasma clearance in the rat in vivo. These compounds were also acetylated in
      human liver cytosol and the N-acetyl metabolite was a major metabolite formed in
      incubations with cryopreserved human hepatocytes. 4. Using specific inhibitors,
      correlation analysis and expressed human N-acetyltransferase (NAT) enzymes the
      compounds were shown to be substrates of the polymorphically expressed NAT-2
      isozyme. 5. Further experiments showed that it was possible to make small
      structural changes to the piperazine group that retained potency but prevented
      metabolism by NAT.

PMID- 18720283
TI  - Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin.
AB  - Atorvastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
      inhibitor that is mainly metabolized by cytochrome P450 (CYP) 3A4. A recent study
      showed that the lipid-lowering effect of statins is affected by the CYP3A5
      polymorphism. Therefore, it was investigated whether CYP3A5 contributes to the
      metabolism of atorvastatin. Two metabolites of atorvastatin, para- and ortho
      hydroxyatorvastatin, were produced by human liver microsomes and human
      recombinant CYP3A enzymes, and the enzyme kinetic pattern exhibited substrate
      inhibition. The intrinsic clearance (CL(int)) rates of para- and ortho
      hydroxyatorvastatin by CYP3A4 were 2.4- and 5.0-fold of the respective CL(int)
      rates of CYP3A5, indicating that CYP3A4 is the major P450 isoform responsible for
      atorvastatin metabolism. These results suggest that atorvastatin is
      preferentially metabolized by CYP3A4 rather than by CYP3A5, and thus the genetic
      CYP3A5 polymorphism might not be an important factor in the inter-individual
      variation of atorvastatin disposition and pharmacodynamics in human.

PMID- 18720284
TI  - Pseudocolor transformation for visualization of ossicles in CT images.
AB  - CONCLUSION: Pseudocolor transformation demonstrated partial efficiency for
      increasing the visibility of the stapes and the incudostapedial (IS) joint in CT
      images. Variable color transformation could be examined in the future for
      increasing detection of otologic lesions. OBJECTIVES: Pseudocolor transformation
      is a technique for artificially assigning colors to a gray scale. This study was
      undertaken to evaluate the efficiency of the pseudocolor transformation technique
      for the visualization of ossicles in temporal bone CT images. SUBJECTS AND
      METHODS: Twenty CT studies of healthy ears were reviewed. CT images were
      transformed to pseudocolor (rainbow scale) with Image-Pro Plus 4.0. software and
      compared with plain images using the following rating scale. For each image one
      of five scores concerning the visibility of the stapes and IS joint was given: 1,
      not seen; 2, probably not seen; 3, not sure; 4, probably seen; 5, definitely
      seen. Visualization sensitivity was determined through statistical analysis using
      a paired t test. RESULTS: The stapes and IS joint were more easily identifiable
      in pseudocolor-transformed images compared with plain images (p<0.05). The oval
      window and footplate were both more easily distinguishable in pseudocolor
      transformed images compared with plain images (p<0.05).

PMID- 18720285
TI  - Response to sang-ho jo.

PMID- 18720287
TI  - Serum concentration of chromogranin A at admission: an early  biomarker of
      severity in critically ill patients.
AB  - BACKGROUND: Chromogranin A (CGA), a stress marker released with catecholamines by
      the adrenal medulla, has never been associated with acute inflammation in
      critically ill patients. AIM: To determine evidence for a link between serum
      concentration of CGA, biomarkers of inflammation, and outcome inpatients admitted
      with or without the systemic inflammatory response syndrome (SIRS). METHODS: At
      admission, we measured in 53 patients and 14 healthy controls the serum
      concentrations of CGA,procalcitonin, and C-reactive protein. We also assessed the
      Simplified Acute Physiological Score (SAPS) in the patients. RESULTS: Serum CGA
      concentrations were significantly increased in SIRS patients with a median value
      of 115 microg/L (68.0-202.8), when compared to healthy controls (PB0.001). In
      cases where infection was associated with SIRS, patients had the highest increase
      in CGA with a median value of 138.5 microg/L (65-222.3) (PB0.001). CGA
      concentrations positively correlated with inflammation markers (procalcitonin, C
      reactive protein), but also with SAPS. Receiver operating characteristic (ROC)
      analysis showed that CGA is equivalent to SAPS as an indicator for 28-day
      mortality (area under curve (AUC) for both: 0.810). CONCLUSIONS: Patients with
      CGA concentration superior to 71 microg/L have a significantly shorter survival.
      A Cox model confirmed that CGA and SAPS were independent predictors of outcome.

PMID- 18720288
TI  - Diacetyl exposures in the flavor manufacturing industry.
AB  - Recently, worker exposures to diacetyl, a chemical used in the production of
      butter popcorn, has been linked to bronchiolitis obliterans, a severe lung
      disease. This chemical is also used in the flavor industry to confer a buttery
      flavor to many food products, with more than 228,000 pounds used in 2005.
      Diacetyl exposures were monitored at 16 small-to medium-sized flavor facilities
      to determine potential diacetyl exposures. A total of 181 diacetyl samples (both
      personal and area samples) were obtained, and a number of real-time samples were
      collected using an IR spectrometer. Samples were obtained during liquid and
      powder compounding operations at the facilities as well as during laboratory and
      QC operations. The personal and area samples ranged from non-detectable (<0.02
      ppm) to as high as 60 ppm. Ninety-two (51%) of the samples were below the limit
      of detection, and the mean diacetyl concentration for all processes was 1.80 ppm.
      Mean diacetyl levels during powder operations were generally higher (4.24 ppm)
      than mean diacetyl levels during liquid operations (2.02 ppm). Maximum real-time
      diacetyl exposures during powder operations could reach as high as 525 ppm. These
      results are similar to exposures measured by NIOSH in popcorn facilities where
      lung disease was found; however, the duration of use and frequency of use may be
      significantly lower.

PMID- 18720289
TI  - Chamber evaluation of a personal, bioaerosol cyclone sampler.
AB  - A personal cyclone sampler (cyclone) was operated in a 0.9-m3 chamber, side by
      side with a 25-mm filter sampler (filter) and either a slit impactor (Air-O-Cell)
      or a single-stage, multiple-hole, agar impactor (N6). Aerosols of two fungal
      spores were collected for 5 min to 5 hr-Aspergillus versicolor: 10, 20, 40, 80,
      160, and 320 min; concentration: 10(2)-10(5) spore m(-3); Scopulariopsis
      brevicaulis: 5, 10, 15, 20, 25, and 30-min; concentration: 10(3)-10(5) spore m(
      3) (six replicates for each sampling time). For each fungus, air concentrations
      were determined by a 15-channel optical particle counter (particle m(-3); N =
      36), microscopy (spore m(-3); cyclone and filter, N = 36; Air-O-Cell, N = 18),
      culture (colony forming unit m(-3); cyclone and filter, N = 36; N6, N = 18), and
      polymerase chain reaction (cell equivalent m(-3); cyclone and filter, N = 36).
      Samplers were significantly correlated with each other as were the three analyses
      (correlation coefficients = 0.79-1.00 and 0.87-0.98, respectively). Ratios were
      calculated for simultaneous measurements with the cyclone and comparison samplers
      and for paired colony:spore, colony:cell equivalent, and cell equivalent:spore
      measurements for the cyclone and filter samples. The cyclone equaled or
      underestimated the other samplers for both fungi and all analyses (mean ratio:
      0.75-1.04). A. versicolor colony and cell equivalent measurements exceeded spore
      measurements although microscopy should detect all spores not just culturable
      ones, perhaps due to difficulty observing the smaller spores or detection of DNA
      in cell fragments in addition to intact spores. Plots of the ratios of paired
      measurements against their averages identified biases between samplers and
      analyses. For example, ratios were correlated with spore concentration, and there
      was greater uncertainty at lower concentrations. These chamber tests have shown
      that the cyclone is suitable for collection of airborne fungal spores over a wide
      concentration range and time period and for analysis by microscopy, culture, and
      polymerase chain reaction.

PMID- 18720290
TI  - Superior discrimination of speech pitch and its relationship to verbal ability in
      autism spectrum disorders.
AB  - Whilst hypersensitivity to pitch information appears to be characteristic of many
      individuals with autism spectrum disorders little is known about the implications
      of such a tendency for language acquisition and development. Discrimination of
      systematically varied pitch differences between pairs of words, nonwords, and
      nonspeech pitch contour analogues was assessed in children with autism spectrum
      disorders (ASD) and matched controls. The findings revealed superior performance
      in ASD, although, like controls, discrimination of pitch in speech stimuli was
      poorer in this group than for nonspeech stimuli. Whilst it was hypothesized that
      enhanced processing of speech pitch would correlate negatively with receptive
      language skills in ASD, the findings did not fully support this, and enhanced
      discrimination skills were observed in individuals without significant language
      impairment. The implications of these findings for understanding heterogeneity of
      language ability in ASD are discussed.

PMID- 18720293
TI  - Surface but not volumetric part structure mediates three-dimensional shape
      representation: evidence from part-whole priming.
AB  - The decomposition of three-dimensional (3-D) objects into shape primitives
      consisting of geometric volumes is a key proposal of some theories of object
      recognition. It implicitly assumes that recognition involves volumetric
      completion--the derivation of a three-dimensional structure that comprises
      inferred shape properties, such as surfaces, that are not directly visible due to
      self-occlusion. The goal of this study was to test this claim. In Experiment 1
      participants memorized novel objects and then discriminated these from previously
      unseen objects. Targets were preceded by primes containing a subset of object
      surfaces that either matched those visible in the whole objects or that could
      only be inferred through volumetric completion. The results showed performance
      benefits through priming from visible surfaces but not from inferred surfaces. In
      Experiment 2, we found equivalent priming for part-primes containing two visible
      surfaces from the same volumetric part and for primes containing one surface from
      each of two volumes. These results challenge the view that 3-D object recognition
      is mediated by shape primitives comprising geometric volumes. Instead, the
      results support an alternative model that proposes that 3-D shapes are
      represented as a non-volumetric surface-based structural description.

PMID- 18720294
TI  - The role of attention during retrieval in working-memory span: a dual-task study.
AB  - We tested the hypothesis that retrieving target words in operation span (OSpan)
      involves attention-demanding processes. Participants completed the standard OSpan
      task and a modified version in which all equations preceded all target words.
      Recall took place under either full attention or easy versus hard divided
      attention conditions. Recall suffered under divided attention with the recall
      decrement being greater for the hard secondary task. Moreover, secondary-task
      performance was disrupted more by the standard OSpan task than by the modified
      version with the hard secondary task showing the larger decrement. Finally, the
      time taken to start recalling the first word was considerably longer for the
      standard version than for the modified version. These results are consistent with
      the proposal that successful OSpan task performance in part involves the
      attention-demanding retrieval of targets from long-term memory.

PMID- 18720299
TI  - Dedication: Professor Ronald A. Asherson, M.D. (Hon), F.R.C.P., M.D., F.A.C.P.,
      F.C.P., F.A.C.R., Dip. O&G (Hon) [1934-2008].

PMID- 18720300
TI  - Antiphospholipid antibodies and the antiphospholipid syndrome. I: pathogenesis,
      clinical features, diagnosis, and management. Preface.

PMID- 18720301
TI  - Primary, secondary, and catastrophic antiphospholipid syndrome: what's in a name?
AB  - The association of the lupus anticoagulant with thrombosis and recurrent
      pregnancy loss was first recognized over a 20-year period between the early 1960s
      and early 1980s. The introduction of the anticardiolipin test in 1983 and the
      recognition of its association with clinical features similar to the lupus
      anticoagulant led to an exponential growth of interest in this disorder. The
      belief that anticardiolipin antibodies and lupus anticoagulant belonged to the
      family of antiphospholipid antibodies led to the disorder being named the
      antiphospholipid syndrome (APS). Efforts by individual investigators to introduce
      criteria for classification of APS and to standardize anticardiolipin antibody
      and lupus anticoagulant tests were started in the mid-1980s to ensure more
      reliable recognition and treatment of affected patients. Another layer of
      complexity was introduced with recognition that many anticardiolipin antibody
      positive sera also bound the antigen beta (2) glycoprotein I. With increasingly
      sophisticated epidemiologic and prospective studies in the 1990s, more structured
      and better-documented criteria for APS were introduced in 1999 and modified in
      2006. These criteria have been widely adopted. Whereas data supporting
      subclassification of APS into primary and secondary subgroups remain tenuous, a
      small percentage of patients do appear subject to clinical features termed the
      catastrophic antiphospholipid syndrome. Introduction of classification criteria
      for APS has enabled more reliable prospective studies, the promise of better
      management, and more valid tests for recognition of the disorder.

PMID- 18720302
TI  - The primary, secondary, catastrophic, and seronegative variants of the
      antiphospholipid syndrome: a personal history long in the making.
AB  - Although many of the clinical features accompanying lupus anticoagulant
      positivity were documented in the early 1960s and many "non-lupus patients" were
      also published, it was not until the discovery of antibodies to cardiolipin in
      the 1980s that the existence and true ramifications of a distinct
      antiphospholipid syndrome was defined. A primary syndrome was in fact recognized
      in 1985 by the author while at the Hammersmith Hospital and comprised 25 patients
      who conformed to this new subset of disease, which has now overtaken lupus
      associated (secondary) antiphospholipid syndromes in frequency. However,
      publication of this important milestone was in fact prevented, because of the
      purveying dogma at that time that "these patients were all suffering from
      'lupus,'" which history has since proved to be incorrect. The syndrome was
      therefore only clearly defined AND published in 1988. Subsequently, in the
      following year, a new and more comprehensive multicenter series comprising 70
      patients was documented (including the original 25 patients from 1985) as well as
      two smaller series by other units. The catastrophic variant of the syndrome with
      distinct triggering factors, clinical features, and a generally poor prognosis
      was then defined in 1992, with more than 300 patients with this devastating
      condition now summarized on the University of Barcelona online registry. The
      existence of a seronegative syndrome has also been suggested, but whether this is
      related to the presence of undetectable antiphospholipid antibodies or perhaps
      represents a similar type of vasculopathy or endotheliopathy is unclear at the
      present time. This article documents a personal account of the events that took
      place in relation to the description of these syndromes.

PMID- 18720303
TI  - Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic
      mechanisms.
AB  - Antiphospholipid antibodies (Abs) are associated with thrombosis and are a risk
      factor for recurrent pregnancy loss and obstetric complications in patients with
      the antiphospholipid syndrome. It is generally accepted that the major
      autoantigen for aPL Abs is beta (2) glycoprotein I, which mediates the binding of
      aPL Abs to target cells (i.e., endothelial cells, monocytes, platelets,
      trophoblasts, etc.) leading to thrombosis and fetal loss. This article addresses
      molecular events triggered by aPL Abs on endothelial cells, platelets, and
      monocytes and complement activation, as well as a review of the current knowledge
      with regard to the putative receptor(s) recognized by aPL Abs on target cells as
      well as novel mechanisms that involve fibrinolytic processes. A section is
      devoted to the description of thrombotic and inflammatory processes that lead to
      obstetric complications mediated by aPL Abs. Based on experimental evidence using
      in vitro and in vivo models, new targeted therapies for treatment and/or
      prevention of thrombosis and pregnancy loss in antiphospholipid syndrome are
      proposed.

PMID- 18720304
TI  - Novel considerations in the pathogenesis of the antiphospholipid syndrome:
      involvement of the tissue factor pathway of blood coagulation.
AB  - The antiphospholipid syndrome (APS) is characterized by clinical manifestations
      such as venous and arterial thrombosis, thrombocytopenia and/or recurrent
      pregnancy loss, as well as the persistent presence of laboratory markers of
      antiphospholipid (aPL) antibodies detected in laboratory assays. Though it is
      generally accepted that aPL antibodies, such as anticardiolipin (aCL), anti-beta2
      glycoprotein I (anti-beta2GPI), and lupus anticoagulants (LA) contribute to the
      pathogenesis of APS, precise mechanism(s) are yet to be fully described. It is
      probable that aPL antibodies bind to a range of cellular targets (e.g.,
      platelets, endothelial cells, and monocytes), leading to thrombosis and obstetric
      complications. There is now increasing evidence that alterations to the tissue
      factor (TF) pathway of blood coagulation contribute toward hypercoagulability in
      patients with aPL antibodies. This article reviews current evidence that suggests
      changes and/or interference to the major pathway of blood coagulation may
      represent a novel mechanism that contributes to the development of APS.

PMID- 18720305
TI  - Antiphospholipid antibodies and the antiphospholipid syndrome: clinical
      significance and treatment.
AB  - This article provides a review of the various types of antiphospholipid (aPL)
      antibodies and antiphospholipid syndromes, their prevalence, presumed origin,
      relationship to autoimmunity in general, and their role in the body's defenses
      and apoptosis. New hypotheses such as the role of antibodies to beta2
      glycoprotein I (beta2GPI) and the signaling of toll-like receptors are also
      discussed, as is the spectrum of clinical manifestations associated with the
      demonstration of these antibodies, now assumed to be "pathogenic." A distinction
      is made between antibodies present in sera of patients with a variety of
      microangiopathic syndromes (MAPS; e.g., HELLP syndrome, thrombotic
      thrombocytopenic purpura, and thrombotic microangiopathic syndromes). In these
      conditions, the antibodies might not be "pathogenic" but, alternatively,
      generated by small vessel endothelial damage. These conditions are differentially
      referred to as microangiopathic antiphospholipid-associated syndromes, and they
      should be differentiated from the microvascular occlusions that are seen in the
      antiphospholipid syndrome. Current treatments of the antiphospholipid syndrome
      are briefly reviewed.

PMID- 18720307
TI  - Pediatric antiphospholipid antibodies and antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) can occur in children, like adults, with the same
      diverse spectrum of thrombotic sites but predominately with deep vein thrombosis
      and stroke. In contrast with adults, however, transient nonthrombogenic
      antiphospholipid (aPL) antibodies are seen more commonly, usually after childhood
      infections. In those with "true" aPL antibodies, recurrent thrombotic events seem
      less frequent than in adults, perhaps reflecting the less prothrombotic
      hemostatic state of childhood. Children with thrombotic events in APS present
      difficult management problems, as there is little evidence-based medicine. The
      duration and intensity of anticoagulation are unresolved management issues, but a
      target international normalized ratio of 2 to 3 is used by most. Multicenter
      randomized controlled trials would provide answers to some of these issues but
      are difficult to organize due to ethical issues and the rarity of the condition.
      A pediatric APS registry such as the Ped-APS Register is more easy to organize
      and can yield informative data.

PMID- 18720306
TI  - Lupus and the antiphospholipid syndrome in pregnancy and obstetrics: clinical
      characteristics, diagnosis, pathogenesis, and treatment.
AB  - The antiphospholipid syndrome (APS) in pregnancy is associated with repeated
      miscarriages and fetal loss. Other complications of pregnancy such as
      preeclampsia and placental insufficiency are also frequently reported during
      pregnancy in APS. The pathogenesis of pregnancy failures in APS is related to
      both the thrombophilic effect of antiphospholipid antibodies and also to
      different mechanisms including a direct effect of antibodies on trophoblast
      differentiation and invasion. Although optimal pharmacologic treatment is
      essential to achieve a successful outcome in APS pregnancy, the standard APS
      pharmacologic treatment alone may not be sufficient. A good obstetric outcome is
      the result of careful obstetric monitoring, proper delivery timing, and skillful
      neonatal care. A multidisciplinary team (obstetricians, rheumatologists, and
      neonatologists) and the progress in neonatal intensive care are as important as
      drugs in achieving a good obstetric outcome and to reduce the possible
      consequences of premature delivery.

PMID- 18720308
TI  - Antiphospholipid antibodies and antiphospholipid syndrome in patients with
      malignancies: features, incidence, identification, and treatment.
AB  - Thrombotic events associated with antiphospholipid (aPL) antibodies can be the
      first manifestation of malignancy. The pathologic significance of aPL antibodies
      in patients with malignancies, however, is still unclear. It remains an
      unresolved issue as to whether the presence of aPL antibodies may be considered
      as an "epiphenomenon" of the malignancy itself or whether it contributes directly
      to the development of thrombosis in these patients. In particular, solid tumors
      may be associated with the development of aPL antibodies, enhancing the
      thrombophilic risk in these patients. In general, routine anticoagulant
      prophylaxis with low-molecular-weight heparin in cancer patients with positive
      aPL antibodies is strongly indicated.

PMID- 18720309
TI  - Neurologic symptoms as a feature of the antiphospholipid syndrome.
AB  - Antiphospholipid antibodies may cause various neurologic diseases by vascular and
      immune mechanisms. Ischemic stroke and transient ischemic attacks are the most
      common neurologic complications in patients with antiphospholipid antibodies but
      migraine, epilepsy, chorea, or multiple sclerosis also may occur. Although the
      neurologic presentation of patients with the antiphospholipid syndrome may vary,
      many patients have striking similarities, such as initial memory loss, aphasia,
      cognitive dysfunction with progressive cerebral deterioration, and even dementia.
      In conclusion, antiphospholipid syndrome may constitute a treatable cause of
      neurologic diseases, and the measurement of antiphospholipid antibodies should be
      routinely performed in patients with neurologic disorders.

PMID- 18720310
TI  - Morbidity and mortality in the catastrophic antiphospholipid syndrome:
      pathophysiology, causes of death, and prognostic factors.
AB  - The catastrophic variant of the antiphospholipid syndrome (APS) is a condition
      characterized by multiple vascular occlusive events, usually affecting small
      vessels and evolving over a short period of time, together with laboratory
      confirmation of the presence of antiphospholipid antibodies. The pathogenesis of
      catastrophic APS is not completely understood. The mortality rate was ~50% in the
      earliest published series, but recently it has clearly fallen by some 20% due to
      the use, as first-line therapies, of full anticoagulation, corticosteroids,
      plasma exchanges, and intravenous immunoglobulins. Cerebral involvement has been
      identified as the main cause of death, being present in one third of patients,
      and consisting mainly of stroke, cerebral hemorrhage and encephalopathy, followed
      by cardiac involvement and infection. The only identified prognostic factor for a
      higher mortality rate is the presence of systemic lupus erythematosus.

PMID- 18720311
TI  - Clinical features, diagnosis, and management of the antiphospholipid syndrome.
AB  - Almost 30 years after it was first described as a discrete clinical entity, the
      antiphospholipid syndrome (APS) remains a challenge for clinicians in a wide
      range of specialities. There remain ongoing issues regarding nomenclature, the
      expanding range of clinical manifestations, and management of certain APS patient
      subgroups. In addition to the presence of appropriate clinical features, the
      diagnosis of APS also fundamentally requires the finding of positive
      antiphospholipid antibody test result(s), and unfortunately much still has to be
      done to improve the robustness, reproducibility, and standardization of these
      assays. This article discusses ongoing dilemmas and issues related to clinical
      aspects of APS including (i) the derivation of the current nomenclature and the
      implications of recent proposals for its revision; (ii) the problems that the
      protean clinical manifestations pose for many clinicians, in particular those not
      intimately familiar with APS; (iii) the potential pitfalls of applying the APS
      classification criteria as diagnostic criteria (although no doubt tempting for
      nonspecialist clinicians); (iv) the concept of seronegative APS and the effect
      that recent proposed changes in antiphospholipid antibody testing strategies may
      have on this diagnosis; and finally (v) an overview of key developments in the
      clinical management of APS patients over the past 30 years.

PMID- 18720314
TI  - Dynamic interactions of language with other cognitive processes.

PMID- 18720315
TI  - Models of attention and dual-task performance as explanatory constructs in
      aphasia.
AB  - Aphasia has traditionally been viewed as a loss or impairment of language.
      However, evidence is presented suggesting that language mechanisms are
      fundamentally preserved and that aphasic language behaviors are instead due to
      impairments of cognitive processes supporting their construction. These processes
      may be understood as a linguistically specialized attentional system that is
      vulnerable to competition from other processing domains. We present two models of
      attention that focus on competition for central processing and discuss findings
      from dual-task studies of normal and aphasic performance. First, competing
      language and nonlanguage tasks appear to share limited-capacity, parallel
      processing resources. Second, aphasic individuals demonstrate slowed central
      processing that could be due to a reduction in processing capacity or ability to
      allocate that capacity. Third, the attention models discussed bear a coherent
      relationship to current models of language processing. Clinical implications of a
      cognitive processing account of aphasia are also considered.

PMID- 18720316
TI  - An intention manipulation to change lateralization of word production in
      nonfluent aphasia: current status.
AB  - A review of recent aphasia literature indicates that both the left and right
      hemispheres participate, under various circumstances, in recovery of language and
      in treatment response. In chronic aphasias with large lesions and poor recovery
      of function, the right hemisphere is more likely to demonstrate prominent
      activity than in cases with small lesions and good recoveries. Extraneous
      activity during language tasks for aphasia patients may occur in both the left
      and right hemispheres. Right hemisphere activity during language in aphasia
      patients is likely to occur in structures homologous to damaged left hemisphere
      structures. When the left hemisphere is so damaged as to preclude a good
      recovery, recruitment of right-hemisphere mechanisms in the service of
      rehabilitation may be desirable. Hence a treatment with an intention manipulation
      (complex left-hand movement) was developed for nonfluent aphasia to assist in
      relateralization of language production. A review of existing evidence indicates
      that the intention manipulation adds value to naming treatments and helps shift
      lateralization of language production to right frontal structures. However,
      wholesale transfer of language function to the right hemisphere does not occur,
      and residual language knowledge in the left hemisphere also seems vital for
      relearning of word production. Further research is needed to understand fully the
      contribution of the intention manipulation to treatment response.

PMID- 18720318
TI  - The role of computational models in investigating typical and pathological
      behaviors.
AB  - The use of computational models to simulate unimpaired human psychological
      behavior is now fairly common, and use of such models to simulate impaired
      behavior has also increased. In this article I discuss the relation of
      computational models to behavioral investigation and to theory, with a view to
      clarifying what a computational model is, and what its value may be in
      investigating unimpaired and pathological human psychological behavior.

PMID- 18720317
TI  - A disorder of executive function and its role in language processing.
AB  - R. Martin and colleagues have proposed separate stores for the maintenance of
      phonological and semantic information in short-term memory. Evidence from
      patients with aphasia has shown that damage to these separable buffers has
      specific consequences for language comprehension and production, suggesting an
      interdependence between language and memory systems. This article discusses
      recent research on aphasic patients with limited-capacity short-term memories
      (STMs) and reviews evidence suggesting that deficits in retaining semantic
      information in STM may be caused by a disorder in the executive control process
      of inhibition, specific to verbal representations. In contrast, a phonological
      STM deficit may be due to overly rapid decay. In semantic STM deficits, it is
      hypothesized that the inhibitory deficit produces difficulty inhibiting
      irrelevant verbal representations, which may lead to excessive interference. In
      turn, the excessive interference associated with semantic STM deficits has
      implications for single-word and sentence processing, and it may be the source of
      the reduced STM capacity shown by these patients.

PMID- 18720319
TI  - The neural organization of spatial thought and language.
AB  - The cognitive neuroscience of semantics has focused largely on object knowledge.
      By contrast, spatial semantics, especially as related to language, has received
      little attention. Spatial thought and language gives our semantic system a rich
      texture by introducing relational thinking and greater levels of abstraction than
      is evoked by object semantics. This article describes the neural instantiation of
      spatial thought and language based on imaging and lesion studies. We underscore
      two functional-anatomical organizational principles. First, perceptual and
      conceptual representations have a parallel organizational structure within the
      nervous system. Lateral temporal cortices are important for manners of motion,
      action representations, and action verbs. More dorsal regions are important for
      paths of motion, locative representations, and prepositions. Second, posterior
      perceptual representations serve as points of entry for more anterior and
      centripetally located peri-Sylvian conceptual and linguistic representations.

PMID- 18720320
TI  - Speech perceived through a damaged temporal window: lessons from word deafness
      and aphasia.
AB  - Word deafness is an intriguing neurological syndrome characterized by severe
      difficulties in the ability to understand or reproduce spoken language with
      otherwise intact speech production and nonauditory language comprehension. The
      disorder is of significant theoretical importance because it putatively supports
      the modularity of speech recognition from more central language computational
      networks. However, the specificity and functional locus of the processing
      disturbances resulting in word deafness remains unclear. This article discusses
      the nature and potential treatment of word deafness, with particular reference to
      a detailed case study (neuropsychological, neuroimaging, and event-related
      potential) of an adult case of Landau-Kleffner syndrome. The findings in this
      case suggested temporal lobe pathophysiology involving cortical mechanisms
      concerned with temporal processing of rapid frequency changes in sound. We
      propose that these deficits may impede the analysis of linguistically important
      transitional frequency cues in speech and account for the profound difficulties
      in understanding and producing speech. The implications of these findings for
      approaches to the treatment of word deafness are discussed.

PMID- 18720321
TI  - Pregnancy in women with renal disease. Part II: specific underlying renal
      conditions.
AB  - The obstetric outcome in women with kidney disease has improved in recent years
      due to continuous progress in obstetrics and neonatology, as well as better
      medical management of hypertension and renal disease. However, every pregnancy in
      these women remains a high-risk pregnancy. When considering the interaction
      between renal disease and pregnancy, maternal outcomes are related to the initial
      level of renal dysfunction more than to the specific underlying disease. With
      regards to fetal outcomes, though, a distinction may exist between renal
      dysfunction resulting from primary renal disease and that in which renal
      involvement is part of a systemic disease. In part II of this review, some
      specific causes of renal failure affecting pregnancy are considered.

PMID- 18720322
TI  - Dissociation between the effects of oxygen and pressure on matrix
      metalloproteinase-2, -7, and -9 expression in human airway epithelial cells.
AB  - We tested the hypothesis that hyperoxia or pressure exposure differentially
      activates expression of cytokines and/or matrix modeling proteins in human airway
      epithelial cells. Calu-3 epithelial cell monolayers were cultured on transwell
      plates with the apical surface exposed to gas. Following establishment of
      baseline, plates were placed in a chamber and exposed to: control (21% O (2);
      atm), hyperoxia (60% O (2); atm), pressure (21% O (2); 40 cm H (2)O), and
      combination (60% O (2); 40 cm H (2)O). At 72 hour of exposure, monolayers were
      assessed for integrity, viability, and expression of interleukin (IL)-6, IL-8 and
      matrix metalloproteinases (MMPs) -2, -7, and -9. Compared with controls,
      hyperoxia had lower transepithelial resistance ( P < 0.001) and greater IL-6
      secretion ( P < 0.01), and pressure had lower cell viability ( P < 0.001) and
      greater IL-8 secretion ( P < 0.001). Hyperoxia resulted in more latent MMP-2 ( P
      < 0.05) and MMP-7 ( P < 0.001). Pressure was associated with a rise in MMPs
      independent of oxygen exposure ( P < 0.05). Hyperoxia and pressure differentially
      affected MMP activities in Calu-3 cells and may lead to the different functional
      and structural abnormalities observed in these in vitro studies.

PMID- 18720323
TI  - Effects of hypoxic-ischemic encephalopathy and whole-body hypothermia on neonatal
      auditory function: a pilot study.
AB  - We assessed the effects of hypoxic-ischemic encephalopathy (HIE) and whole-body
      hypothermia therapy on auditory brain stem evoked responses (ABRs) and distortion
      product otoacoustic emissions (DPOAEs). We performed serial assessments of ABRs
      and DPOAEs in newborns with moderate or severe HIE, randomized to hypothermia ( N
      = 4) or usual care ( N = 5). Participants were five boys and four girls with mean
      gestational age (standard deviation) of 38.9 (1.8) weeks. During the first week
      of life, peripheral auditory function, as measured by the DPOAEs, was disrupted
      in all nine subjects. ABRs were delayed but central transmission was intact,
      suggesting a peripheral rather than a central neural insult. By 3 weeks of age,
      peripheral auditory function normalized. Hypothermia temporarily prolonged the
      ABR, more so for waves generated higher in the brain stem but the effects
      reversed quickly on rewarming. Neonatal audiometric testing is feasible,
      noninvasive, and capable of enhancing our understanding of the effects of HIE and
      hypothermia on auditory function.

PMID- 18720324
TI  - Diagnosis and management of unilateral third-trimester hydrocephalus: a
      multidisciplinary approach.
AB  - Hydrocephalus is a pathological increase in cerebrospinal fluid. This condition
      may occur when production exceeds absorption. Prior reports describe prenatally
      diagnosed unilateral hydrocephalus with varying outcomes depending on underlying
      brain abnormalities, karyotypic abnormalities, and infection. Prenatal ultrasound
      is a valuable diagnostic tool in the identification of hydrocephalus. Obstacles
      such as near-field artifact, additional intracranial abnormalities, fetal
      positioning, and maternal habitus often make the diagnosis difficult. Antenatal
      diagnosis is important for emotional preparation and for transfer to a tertiary
      center where appropriate facilities and subspecialists are available. We present
      a case of right-sided hydrocephalus and mild left-sided ventriculomegaly
      diagnosed in the third trimester. Fetal brain magnetic resonance imaging
      confirmed the sonographic diagnosis, which allowed the multidisciplinary fetal
      team to meet with the patient and formulate a management plan prior to delivery.

PMID- 18720325
TI  - Diagnosis and prognosis in double-outlet right ventricle.
AB  - The aim of this study was to examine prenatal diagnosis of double-outlet right
      ventricle (DORV)-associated anomalies and prognosis of each case. Medical records
      were reviewed of fetuses with DORV who had fetal echocardiography at our
      institution from 2002 to 2006. Pre- and postnatal diagnosis and outcome were
      compared and evaluated. Twenty-one fetuses were diagnosed with DORV. The
      pregnancy was terminated in seven cases. Three cases had chromosomal
      abnormalities; three cases, hypoplastic left ventricle; and one case,
      encephalocele. Accurate prenatal diagnosis of the ventricular septal defect,
      outflow obstruction, and great artery relationship was achieved in 14 of 16 cases
      (87.5%). Only 2 of 13 live-born cases survived beyond 6 months. The overall
      prognosis for fetuses with DORV is poor. DORV is found in fetuses with a huge
      spectrum of associated cardiac and extracardiac anomalies. Careful assessment by
      fetal echocardiography can determine important anatomic details with adequate
      correctness for precise counseling.

PMID- 18720326
TI  - First case report of a fetal synovial sarcoma confirmed by molecular detection of
      SYT-SSX fusion gene transcripts.
AB  - Synovial sarcomas are aggressive malignant soft tissue tumors typically observed
      in adolescents and young adults. They are often characterized by the chromosomal
      translocation t(X;18)(p11.2;q11.2), which results in the expression of SYT-SSX
      fusion transcripts. We describe the first case of synovial sarcoma observed in a
      human fetus. The tumor occurred in the left upper arm and led to intrauterine
      fetal demise during gestational week 31. Grossly, the tumor measured 10 x 8 x 8
      cm, appeared pinkish in color, and developed in the soft tissues of the left arm
      surrounding the humerus. Histologically, this large tumor showed a dense
      proliferation of homogeneous spindle cells with some necrotic areas. The positive
      detection of the SYT-SSX1 fusion transcripts with reverse-transcription
      polymerase chain reaction in formalin-fixed and paraffin-embedded tissue
      confirmed the synovial sarcoma diagnosis.

PMID- 18720327
TI  - Hemolytic disease of the fetus and newborn due to anti-Ge3: combined antibody
      dependent hemolysis and erythroid precursor cell growth inhibition.
AB  - The Gerbich (Ge) antigens are a collection of high-incidence antigens carried on
      the red blood cell membrane glycoproteins, glycophorins C and D. Antibodies
      against these antigens are uncommon, and there have been only rare case reports
      of hemolytic disease of the fetus and newborn due to anti-Ge. In this case
      report, we present a neonate with severe anemia and hyperbilirubinemia due to
      anti-Ge3. Routine and special laboratory studies undertaken in this case
      suggested two mechanisms for the patient's hemolysis and persistent anemia.
      Antibody-dependent hemolysis was associated with early-onset hyperbilirubinemia,
      anemia, and a mild reticulocytosis, and inhibition of erythroid progenitor cell
      growth was associated with late anemia and normal bilirubin and reticulocyte
      values. Though rare, anti-Ge3 can be a dangerous antibody in pregnancy. Affected
      neonates may require intensive initial therapy and close follow-up for at least
      several weeks after delivery.

PMID- 18720328
TI  - [Picrotoxin in the treatment of Meniere's disease].
AB  - OBJECTIVE: In medical long-term treatment of Meniere's disease picrotoxin
      suppositories are an uncommon method of prophylaxis. In spite of its empirical
      benefit in clinical use and its lack of side effects, there are few clinical
      studies about the therapeutical effect of picrotoxin. In this study we evaluate
      the effectiveness of picrotoxin compared to the therapy with betahistine in
      Meniere's disease. MATERIAL AND METHODS: In a prospective clinical trial we
      examined 41 patients, 18 of them were treated with betahistine 3x12 mg, 23 had a
      therapy with picrotoxin-suppositories at 0.001 g three times a week. Frequency
      and intensity of the vertigo attacks were evaluated before and under treatment.
      Mean follow up time was 12 months. RESULTS: In both groups a reduction of the
      attacks' frequency and intensity could be noticed, which was statistically
      significant for all the two groups. Thus, in the course of the treatment we
      observed a significant stronger effectiveness of picrotoxin, regarding the
      frequency and intensity of vertigo attacks. Discussing our own results we review
      the state of the art in medical long-term treatment in Meniere's disease.
      CONCLUSION: Because of its clinical benefit and the lack of side effects
      Picrotoxin is a reasonable alternative in medical long- term treatment of
      Meniere's disease, which should have an important role in the treatment cascade.

PMID- 18720333
TI  - Cobalt-catalyzed [2+2] cycloaddition.

PMID- 18720329
TI  - [Quality of life and sense of coherence in former German child soldiers of World
      War II].
AB  - OBJECTIVE: The aim of the study was to determine the quality of life and the
      sense of coherence in a sample of former German child soldiers of World War II.
      METHODS: 103 participants were recruited by the press, then administered a Short
      Form-Health-Survey (SF-12), a sense-of-coherence scale (SOC) and 2 qualitative
      questions on possible resources in the combat situation. RESULTS: The quality of
      life was not lowered compared to a comparison group of the same age. The sense of
      coherence was significantly higher than that of the comparison group.
      CONCLUSIONS: The participants belonged to a comparably unobtrusive group of
      veterans. A possible protective variable might be the high sense of coherence.

PMID- 18720334
TI  - Copper-catalyzed enantioselective conjugate addition of dialkylzinc reagents to
      alpha'-oxy enones.

PMID- 18720335
TI  - Controllable synthesis of zinc-substituted alpha- and beta-nickel hydroxide
      nanostructures and their collective intrinsic properties.
AB  - A new controllable homogeneous precipitation approach has been developed to
      synthesize zinc-substituted nickel hydroxide nanostructures with different Zn
      contents from a zinc nanostructured reactant. As typical layered double
      hydroxides (LDHs), zinc-substituted nickel hydroxide nanostructures can be
      formulated as NiZnx(Cl)y(OH)2(1+x)-y.z H2O (x=0.34-0.89, y=0-0.24, z=0-1.36). The
      structure and morphology of zinc-substituted nickel hydroxide nanostructures can
      be systematically controlled by adjustment of the zinc content. The effects of
      temperature and the amounts of ammonia and zinc nanostructured precursor on the
      reaction were systematically investigated. In our new method, although zinc
      substituted alpha-and beta-nickel hydroxides have the typical 3D flowerlike
      architecture and stacks-of-pancakes nanostructures, respectively, their growth
      processes are different from those previously reported. A coordinative
      homogeneous precipitation mechanism is proposed to explain the formation process
      of zinc-substituted nickel hydroxide nanostructures. The zinc-substituted nickel
      hydroxide nanostructures exhibit some interesting intrinsic properties, and
      changing the zinc content can effectively tune their optical, magnetic, and
      electrical properties.

PMID- 18720336
TI  - Conformational choice and selectivity in singly and multiply hydrated
      monosaccharides in the gas phase.
AB  - Factors governing hydration, regioselectivity and conformational choice in
      hydrated carbohydrates have been examined by determining and reviewing the
      structures of a systematically varied set of singly and multiply hydrated
      monosaccharide complexes in the gas phase. This has been achieved through a
      combination of experiments, including infrared ion-depletion spectroscopy
      conducted in a supersonic jet expansion, and computation through molecular
      mechanics, density functional theory (DFT) and ab initio calculations. New
      spectroscopic and/or computational results obtained for the singly hydrated
      complexes of phenyl beta-D-mannopyranoside (beta-D-PhMan), methyl alpha-D-gluco-
      and alpha-D-galactopyranoside (alpha-D-MeGlc and alpha-D-MeGal), when coupled
      with those reported earlier for the singly hydrated complexes of alpha-D-PhMan,
      beta-D-PhGlc and beta-D-PhGal, have created a comprehensive data set, which
      reveals a systematic pattern of conformational preference and binding site
      selectivity, driven by the provision of optimal, co-operative hydrogen-bonded
      networks in the hydrated sugars. Their control of conformational choice and
      structure has been further revealed through spectroscopic and/or computational
      investigations of a series of multiply hydrated complexes; they include beta-D
      PhMan.(H2O)2,3, which has an exocyclic hydroxymethyl group, and the doubly
      hydrated complex of phenyl alpha-L-fucopyranoside, alpha-L-PhFuc.(H2O)2, which
      does not. Despite the very large number of potential structures and binding
      sites, the choice is highly selective with binding invariably "focussed" around
      the hydroxymethyl group (when present). In beta-D-PhMan.(H2O)2,3, the bound water
      molecules are located exclusively on its polar face and their orientation is
      dictated by the (perturbed) conformation of the carbohydrate to which they are
      attached. The possible operation of similar rules governing the structures of
      hydrogen-bonded protein-carbohydrate complexes is proposed.

PMID- 18720337
TI  - New 2-amino-thiazole-4-acetamides with antiplatelet activity.
AB  - In the Born test, 23 title compounds were synthesized and investigated for their
      antiplatelet activities against collagen, ADP, adrenaline, and platelet
      activating factor (PAF) as inducers of the aggregation. Using collagen, three
      compounds with IC(50) values below 10 microM were found (3a, 3b, 3c) and 15
      compounds with IC(50) values between 10 and 100 microM were determined. In
      general, a cyclohexylamino rest on an 4-carboxamide moiety is a pre-requisite for
      this pharmacological activity. A clear dependence from the substituent R(1) in
      the structural element Y is observed. The same is true for the spacer n in the 4
      carboxamide substituent. Compound 3e showed strong ADP-antagonistic effects
      (IC(50) = 2.2 nM); 3c antagonized adrenaline (IC(50) = 2.8 nM), while 3n was
      highly effective against platelet-activating factor (IC(50) = 0.2 microM).

PMID- 18720338
TI  - Novel nitrofurazone derivatives endowed with antimicrobial activity.
AB  - The N-alkylated derivatives from nitrofurazone were synthesised and evaluated in
      vitro for their efficacy as antimicrobial agents against representative strains,
      including methicillin-resistant Staphylococcus aureus (MRSA). The derivative 2a
      demonstrated greater activity than the prototype and was comparable to currently
      used antimicrobial drugs.

PMID- 18720339
TI  - CYP17 inhibitors. Annulations of additional rings in methylene imidazole
      substituted biphenyls: synthesis, biological evaluation and molecular modelling.
AB  - Twenty-one novel compounds originating from two classes of annulated biphenyls
      were synthesized as mimetics of the steroidal A- and C-rings and examined for
      their potency as inhibitors of human CYP17. Selected compounds were tested for
      inhibition of the hepatic CYP enzyme 3A4. Potent CYP17 inhibitors were found for
      each class, compound 9 (17 and 71% at 0.2 and 2 microM, respectively) and 21 (591
      nM). Compound 21 showed only weak inhibition of CYP3A4 (32 and 64% at 2 and 10
      microM, respectively). Both compounds, however, exhibited moderate to strong
      inhibition of the glucocorticoid-forming enzyme CYP11B1. The most interesting
      compounds were docked into our protein model. They bound into one of the modes
      which we have previously published. New interaction regions were identified.

PMID- 18720340
TI  - Synthesis, antibacterial and antifungal activity of some novel 3,5-disubstituted
      1H-1,2,4-triazoles.
AB  - A rapid and efficient one-pot condensation reaction of long-chain alkyl and
      alkenyl acid hydrazides and nitriles was carried out to afford 3,5-disubstituted
      1H-1,2,4-triazoles. The compounds 5a-o were screened for in-vitro antibacterial
      activity against the representative panel of two Gram-positive and two Gram
      negative bacteria. All the synthesized compounds were also tested for their
      inhibitory action against five strains of fungi. The various compounds show
      potent inhibitory action against test organisms. The compounds 5a-o were
      characterized on the basis of elemental analysis and spectral data.

PMID- 18720341
TI  - Synthesis and antiprotozoal evaluation of new N4-(benzyl)spermidyl-linked
      bis(1,3,5-thiadiazinane-2-thiones).
AB  - The synthesis and in-vitro antiprotozoal evaluation of novel N(4)
      (benzyl)spermidyl-linked bis(1,3,5-thiadiazinane-2-thione) (bis-THTT) derivatives
      from N(4)-(benzyl)spermidine is disclosed. Several of the new bis-THTT have in
      vitro activities against L. donovani and T. cruzi that are comparable or superior
      to those of currently employed protozoocidal agents.

PMID- 18720342
TI  - Synthesis of 2,3-disubstituted 1,4-naphthoquinones as antiplatelet agents.
AB  - In continuing search for novel antiplatelet agents, the highly potent agent 2
      chloro-3-methoxycarbonylethylcarboxamido-1,4-naphthoquinone 2 was selected as
      lead compound. Structure-activity relationships in this series were examined.
      Some of these compounds showed significant antiplatelet activities. Further
      studies on the action mechanism showed that 2-acetamido-3-chloro-1,4
      naphthoquinone 4 has a direct inhibitory action on cytosolic phospholipase A(2)
      (cPLA(2)) activity in platelets.

PMID- 18720343
TI  - Synthesis and antituberculosis activity of new hydrazide derivatives.
AB  - The increasing clinical importance of drug-resistant mycobacterial pathogens,
      especially Mycobacterium tuberculosis, has lent additional urgency to
      microbiological research and new antimycobacterial compound development. For this
      purpose, new hydrazide derivatives of imidazo[1,2-a]pyridine were synthesized and
      evaluated for antituberculosis activity. The reaction of 2-[(2-carboxyimidazo[1,2
      a]pyridine-3-yl)sulfanyl]acetic acid hydrazide with various benzaldehydes gave N
      (arylidene)-2-[(2-carboxyimidazo[1,2-a]pyridine-3-yl)sulfanyl]acetic acid
      hydrazide derivatives. The chemical structures of the compounds were elucidated
      by IR,(1)H-NMR, FAB-MS spectral data and elemental analysis. Antituberculosis
      activities of the synthesized compounds were determined by broth microdilution
      assay, the Microplate Alamar Blue Assay in BACTEC 12B medium. The results were
      screened in vitro, using the BACTEC 460 Radiometric System against Mycobacterium
      tuberculosis H37Rv (ATCC 27294) at 6.25 microg/mL; the tested compounds showed
      significant inhibition.

PMID- 18720344
TI  - Soybean allergen detection methods--a comparison study.
AB  - Soybean containing products are widely consumed, thus reliable methods for
      detection of soy in foods are needed in order to make appropriate risk assessment
      studies to adequately protect soy allergic patients. Six methods were compared
      using eight food products with a declared content of soy: a direct sandwich ELISA
      based on polyclonal rabbit antibody (ab) to raw soy flakes, a commercial and an
      in-house competitive ELISA both based on ab to denatured, 'renatured' soy
      protein, an enzyme-allergosorbent test (EAST) inhibition based on two sera from
      soy allergic patients, histamine release (HR) using basophils passively
      sensitized with patient serum and a PCR method detecting soy DNA. Eight food
      products were selected as model foods to test the performance of the methods.
      There was an overall good agreement between the methods in terms of ranks of soy
      content but not the quantity. The sandwich ELISA aimed at native soy proteins had
      the lowest detection limit of 0.05 ppm, but only identified soy in 5/8 products,
      and generally in lower amounts compared to other methods. The competitive ELISA
      had a higher detection limit of 21 ppm, but seemed more successful in detecting
      processed soy. Only HR, EAST inhibition and PCR detected soy in all eight
      products. In spite of a general good correlation in terms of ranks of soy
      content, more than a single method may be necessary to confirm the presence of
      soy in foods.

PMID- 18720345
TI  - Antiglycative and anti-VEGF effects of s-ethyl cysteine and s-propyl cysteine in
      kidney of diabetic mice.
AB  - Antiglycative and antivascular endothelial growth factor (VEGF) effects of s
      ethyl cysteine (SEC), and s-propyl cysteine (SPC) in kidney of diabetic mice were
      examined. SEC and SPC at 1 and 2 g/L were added to the drinking water for 12 wk.
      Results showed that diabetic mice with SEC or SPC intake had significantly higher
      final body weight, lower kidney weight, lower levels of plasma glucose, urinary
      albumin (UA), and urinary creatinine (UC) (p < 0.05), in which dose-dependent
      effects were observed in reducing plasma glucose, UA, and UC (p < 0.05). The
      intake of these compounds significantly and dose-dependently decreased the levels
      of plasma glycated hemoglobin (HbA1c), renal carboxymethyllysine and urinary
      glycated albumin (p < 0.05). SEC or SPC intake significantly and dose-dependently
      diminished renal aldose reductase (AR) activity and enhanced glyoxalase I (GLI)
      activity (p < 0.05); also significantly decreased renal sorbitol and fructose
      concentrations (p < 0.05). The intake of SEC or SPC significantly lowered renal
      VEGF level (p < 0.05), and caused dose-dependent downregulation in AR mRNA
      expression, and upregulation in GLI mRNA expression (p < 0.05). Our present study
      suggests the supplement of SEC or SPC might be helpful for the prevention or
      treatment of diabetic kidney diseases via alleviating renal glycative injury.

PMID- 18720346
TI  - Selenoprotein deficiency enhances radiation-induced micronuclei formation.
AB  - The availability of selenium and the levels of specific selenoproteins might
      affect cancer risk by influencing the ability of DNA damaging agents to cause
      genomic instability and mutations. Transgenic mice that express reduced levels of
      selenoproteins and previously shown to be more susceptible to pathology
      associated with cancer development were used to study this possibility. These
      mice were exposed to X-rays and DNA damage assessed in the erythrocytes, where
      micronuclei formation was higher compared to the same cells obtained from
      irradiated wild-type controls. To determine whether the selenoprotein glutathione
      peroxidase-1 (GPx-1) might be involved in this protection, its levels were
      reduced by siRNA targeting in LNCaP human prostate cells. UV-induced micronuclei
      frequency was higher in these cells compared to control-transfected cells. These
      results indicate a role for selenoproteins in protecting DNA from damage and
      support human data implicating GPx-1 as a possible target of the chemoprotective
      effect of selenium.

PMID- 18720347
TI  - Metabolism of curcumin and induction of mitotic catastrophe in human cancer
      cells.
AB  - In cultured cells, curcumin (CUR) causes cell death by interfering with mitosis
      and leading to fragmented nuclei and disrupted microtubules, a process named
      mitotic catastrophe. In order to clarify the role of the known CUR metabolites
      hexahydro-CUR (HHC) and CUR-glucuronide (CUR-gluc) in mitotic catastrophe, the
      effects of CUR were studied in three human cancer cell lines with different
      metabolism of CUR. In Ishikawa and HepG2 cells, CUR was metabolized to HHC and
      small amounts of octahydro-CUR (OHC), whereas the only metabolism in HT29 cells
      was the formation of CUR-gluc. Despite their different metabolism, all three cell
      systems responded to CUR with arrest in G2/M phase and mitotic catastrophe.
      Fractionation of the cells showed that concentrations of CUR were higher in the
      ER and cytosol than in the incubation medium by a factor of up to about 150 and
      8, respectively. In contrast to CUR, the metabolite HHC and the products of
      spontaneous degradation did not elicit any effects in Ishikawa cells. These
      results imply that the causative agent of mitotic catastrophe is the parent CUR
      molecule, whereas reductive metabolism and chemical degradation render CUR
      inactive.

PMID- 18720349
TI  - Enantioselective synthesis of the fully functionalized ABC ring of zoanthenol.
AB  - Zoanthenol, isolated from Zoanthus sp., possesses an extremely complex
      architecture including contiguous quaternary carbons. An enantioselective
      synthesis of the fully functionalized ABC-ring of zoanthenol has been achieved
      and is described herein. The key features of the synthesis are the enzymatic
      kinetic optical resolution and the Mizoroki-Heck/Simmons-Smith reaction strategy
      used to construct the congested asymmetric quaternary carbons.

PMID- 18720348
TI  - Dietary procyanidins lower triglyceride levels signaling through the nuclear
      receptor small heterodimer partner.
AB  - Hypertriglyceridemia is an independent risk factor in the development of
      cardiovascular diseases, and we have previously reported that oral administration
      of a grape seed procyanidin extract (GSPE) drastically decreases plasma levels of
      triglycerides (TG) and apolipoprotein B (ApoB) in normolipidemic rats, with a
      concomitant induction in the hepatic expression of the nuclear receptor small
      heterodimer partner (NR0B2/SHP). Our objective in this study was to elucidate
      whether SHP is the mediator of the reduction of TG-rich ApoB-containing
      lipoproteins triggered by GSPE. We show that GSPE inhibited TG and ApoB secretion
      in human hepatocarcinoma HepG2 cells and had and hypotriglyceridemic effect in
      wild-type mouse. The TG-lowering action of GSPE was abolished in HepG2 cells
      transfected with a SHP-specific siRNA and in a SHP-null mouse. Moreover, in mouse
      liver, GSPE downregulated several lipogenic genes, including steroid response
      element binding protein 1c (SREBP-1c), and upregulated carnitine
      palmitoyltransferase-1A (CPT-1A) and apolipoprotein A5 (ApoA5), in a SHP
      dependent manner. In HepG2 cells GSPE also inhibited ApoB secretion, but in a SHP
      independent manner. In conclusion, SHP is a key mediator of the
      hypotriglyceridemic response triggered by GSPE. This novel signaling pathway of
      procyanidins through SHP may be relevant to explain the health effects ascribed
      to the regular consumption of dietary flavonoids.

PMID- 18720350
TI  - A geometric confidence ellipse approach to the estimation of the ratio of two
      variables.
AB  - One is often interested in the ratio of two variables, for example in genetics,
      assessing drug effectiveness, and in health economics. In this paper, we derive
      an explicit geometric solution to the general problem of identifying the two
      tangents from an arbitrary external point to an ellipse. This solution permits
      numerical integration of a bivariate normal distribution over a wedge-shaped
      region bounded by the tangents, which yields an evaluation of the tangent slopes
      as confidence limits on the ratio of the component variables. After suitable
      adjustment of the confidence coverage of the ellipse, these confidence limits are
      shown to be equivalent to those from Fieller's method. However, the geometric
      approach allows additional interpretation of the data through identification of
      the points of tangency, the ellipse itself, and expressions for the coverage
      probability of the confidence interval. Numerical evaluations using the
      theoretical expressions for the geometric confidence intervals (but ignoring
      sample variation in the underlying parameters) suggested that they perform well
      overall and are slightly conservative. Simulations that do take account of sample
      variation in the underlying parameters again suggested that the intervals perform
      well overall, although here they are slightly anti-conservative. Coverage
      probabilities for the confidence intervals were only weakly dependent on the
      distance and correlation of the ellipse, but there were asymmetries in the
      failure rates of the upper and lower confidence limits in some configurations.
      The probability of no real solution existing was also evaluated. These ideas are
      illustrated by a practical example.

PMID- 18720351
TI  - Score and profile likelihood confidence intervals for contingency table
      parameters.
AB  - A straightforward approach to computing score and profile likelihood confidence
      intervals for contingency table parameters is described. The computational
      approach herein avoids two main limitations of existing methods: (1) Compared
      with existing methods, this paper's approach is applicable to a much broader
      class of parameters. (2) Unlike existing methods, this paper's approach is not
      case-specific and, hence, lends itself to a general, yet very simple,
      computational algorithm. This paper describes the 'sliding quadratic'
      computational algorithm and illustrates its use on examples that have not been
      previously considered in the literature. A small-scale simulation study
      highlights the advantage of using score and profile likelihood intervals rather
      than Wald intervals.

PMID- 18720352
TI  - Mesostructured forms of the transition phases eta- and chi-Al2O3.

PMID- 18720353
TI  - [Sn17{GaCl(ddp)}4]: a high-nuclearity metalloid tin cluster trapped by
      electrophilic gallium ligands.

PMID- 18720354
TI  - Mass spectrometry for structural characterization of therapeutic antibodies.
AB  - Antibodies, also known as immunoglobulins, have emerged as one of the most
      promising classes of therapeutics in the biopharmaceutical industry. The need for
      complete characterization of the quality attributes of these molecules requires
      sophisticated techniques. Mass spectrometry (MS) has become an essential
      analytical tool for the structural characterization of therapeutic antibodies,
      due to its superior resolution over other analytical techniques. It has been
      widely used in virtually all phases of antibody development. Structural features
      determined by MS include amino acid sequence, disulfide linkages, carbohydrate
      structure and profile, and many different post-translational, in-process, and in
      storage modifications. In this review, we will discuss various MS-based
      techniques for the structural characterization of monoclonal antibodies. These
      techniques are categorized as mass determination of intact antibodies, and as
      middle-up, bottom-up, top-down, and middle-down structural characterizations.
      Each of these techniques has its advantages and disadvantages in terms of
      structural resolution, sequence coverage, sample consumption, and effort required
      for analyses. The role of MS in glycan structural characterization and profiling
      will also be discussed.

PMID- 18720355
TI  - Primary-amine-catalyzed enantioselective intramolecular aldolizations.

PMID- 18720356
TI  - Results of the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and
      dexamethasone regimen in elderly patients with acute lymphocytic leukemia.
AB  - BACKGROUND: Understanding the causes of failure in older patients with acute
      lymphocytic leukemia (ALL) may help improve treatment strategies for patients in
      this particular age group. METHODS: The objectives of the current study were to
      define the causes of death in older patients (aged > or = 60 years) with ALL
      during induction and consolidation-maintenance with a dose-intensive regimen of
      alternating 8 courses of hyperfractionated cyclophosphamide, vincristine,
      doxorubicin, and dexamethasone (hyper-CVAD) with high doses of methotrexate and
      cytarabine followed by maintenance with 6-mercaptopurine, vincristine,
      methotrexate, and prednisone and to compare their outcomes with the outcomes of
      older patients who received earlier, less intensive regimens and younger patients
      who received hyper-CVAD. One hundred twenty-two older patients who received hyper
      CVAD were compared with 34 older patients who received less intensive regimens
      and with 409 younger patients who received hyper-CVAD. RESULTS: The complete
      response (CR) rates in older patients receiving hyper-CVAD, older patients
      receiving other regimens, and younger patients receiving hyper-CVAD were 84%,
      59%, and 92%, respectively (P < .001); and the respective induction mortality
      rates were 10%, 12%, and 2% (P not significant in older patients). The incidence
      of disease resistance during induction was 5%, 27%, and 2%, respectively (P <
      .001). The majority of deaths were related to infections. Among patients who
      achieved a CR, death in CR was noted in 34%, 15%, and 7% of older patients
      receiving hyper-CVAD, older patients receiving other regimens, and younger
      patients, respectively (P < .001); and the respective rates of recurrence were
      40%, 80%, and 48% (P = .004). The estimated 5-year survival rates were 20%, 9%,
      and 48%, respectively (P < .001). CONCLUSIONS: The results of the current study
      suggested that intensifying the chemotherapy in older patients with ALL reduced
      the incidence of leukemia resistance but increased the incidence of death in CR
      from myelosuppression-associated infections. The overall benefit:risk ratio was
      favorable. Identifying novel, low-intensity agents/regimens for older patients
      with ALL may improve the results further.

PMID- 18720357
TI  - The design of a LiFePO4/carbon nanocomposite with a core-shell structure and its
      synthesis by an in situ polymerization restriction method.

PMID- 18720358
TI  - Treatment and survival outcomes based on histologic grading in patients with head
      and neck mucoepidermoid carcinoma.
AB  - BACKGROUND: Histopathologic grade of mucoepidermoid carcinoma (MEC) is an
      established predictor of prognosis and affects treatment protocol. Tumor behavior
      is more aggressive in high-grade than in low-grade MEC, leading to a more
      intensive treatment protocol. Outcomes for patients with intermediate-grade MEC
      are less clear; therefore, the optimal treatment protocol for this group is not
      well defined. The treatment protocol and survival outcomes of patients treated
      for MEC of the head and neck was investigated. METHODS: A retrospective clinical
      review and prospective review of histopathologic grading were undertaken using
      the most recently established grading system of 50 patients with MEC of the head
      and neck from 1983 through 2004. RESULTS: As histologic grade increased from low
      to intermediate to high, overall survival (P < .0001) and disease-free survival
      (P < .001) were significantly decreased. Overall and disease-free survival were
      significantly better for patients with intermediate-grade MEC than those with
      high-grade disease. Overall and disease-free survival were similar for patients
      with low-grade and intermediate-grade MEC. There was a low rate of disease
      recurrence in patients with intermediate-grade MEC, but this did not lead to
      death from disease. Although no patients with low-grade or intermediate-grade MEC
      died of disease, 52% of patients with high-grade MEC died of disease.
      Multivariate analysis revealed that histologic grade, age, and surgical margin
      status significantly predicted prognosis. CONCLUSIONS: These findings suggest
      that, under the current histopathologic classification system, the behavior of
      intermediate-grade MEC is comparable to that of low-grade MEC and different from
      high-grade MEC, allowing for the establishment of an evidence-based treatment
      protocol.

PMID- 18720360
TI  - Anticoagulation for the initial treatment of venous thromboembolism in patients
      with cancer: a systematic review.
AB  - BACKGROUND: The authors compared the relative efficacy and safety of low
      molecular-weight heparin (LMWH) and unfractionated heparin (UFH) for the initial
      treatment of venous thromboembolism (VTE) between patients with and without
      cancer. METHODS: By using Cochrane methodology for systematic reviews, separate
      meta-analyses were conducted for subgroups of patients with and without cancer,
      and relative risks (RRs) were compared for statistical significance. The
      methodologic quality for each outcome was assessed by using the Grading of
      Recommendations Assessment, Development, and Evaluation approach. RESULTS: LMWH
      reduced mortality significantly compared with UFH in patients with cancer (RR of
      0.71; 95% confidence interval [95% CI], 0.52-0.98 [moderate-quality evidence])
      but not in patients without cancer (RR of 0.97; 95% CI, 0.65-1.46 [low-quality
      evidence]). However, the difference in the RR for the 2 subgroups did not reach
      statistical significance (P = .113). The difference between LMWH and UFH in the
      effect on recurrent VTE was not statistically significant in the subgroup with
      cancer (RR of 0.78; 95% CI, 0.29-2.08 [low-quality evidence]), in the subgroup
      without cancer (RR of 0.94; 95% CI, 0.60-1.46 [low-quality evidence]), or between
      the 2 subgroups (P = .367). No data were available for bleeding outcomes,
      thrombocytopenia, or postphlebitic syndrome. CONCLUSIONS: The current results
      indicated that LMWH most likely is superior to UFH in reducing mortality in the
      initial treatment of VTE for patients with cancer. There is a need for more and
      better designed trials to confirm these findings.

PMID- 18720359
TI  - Immunohistochemical markers associated with brain metastases in patients with
      nonsmall cell lung carcinoma.
AB  - BACKGROUND: To the authors' knowledge, there are no reliable markers able to
      identify patients with nonsmall cell lung cancer (NSCLC) that will develop
      metastases to the brain. The authors investigated associations between
      immunohistochemical markers and the development of brain metastases in patients
      with NSCLC. METHODS: This was a hospital-based, case-control study of patients
      who were newly diagnosed with NSCLC between 1989 and 2003, developed brain
      metastases, and had pathology material available from both the primary NSCLC and
      the brain metastases. These patients were compared with a control group of
      patients who had NSCLC and no evidence of brain metastases. NSCLC was examined
      for expression levels of Ki-67, caspase-3, vascular endothelial growth factor A
      (VEGF-A), VEGF-C, E-cadherin, and epidermal growth factor receptor (EGFR) in 54
      surgical pathology specimens using immunohistochemistry, and associations were
      evaluated between those markers and the development of brain metastases. RESULTS:
      Brain metastases developed after a median of 12.5 months (range, 1.7-89.4 months)
      after the diagnosis of NSCLC. A significantly increased risk of developing brain
      metastases was associated with patients with NSCLC who had primary tumors with
      high Ki-67 levels (adjusted odds ratio [OR] of 12.2; 95% confidence interval [95%
      CI], 2.4-70.4 [P < .001]), low caspase-3 expression (adjusted OR of 43; 95% CI,
      5.3 to >100 [P < .001]), high VEGF-C expression (adjusted OR of 14.6; 95% CI, 2.0
      to >100 [P < .001]), and low E-cadherin (adjusted OR of 3.6; 95% CI, 0.9-16.4 [P
      = .05]). No significant risk was associated with VEGF-A or EGFR expression. High
      Ki-67 expression also was associated with a shorter overall survival (P = .04).
      CONCLUSIONS: The results of the current study indicated that patients with NSCLC
      who had high Ki-67 expression, low caspase-3 expression, high VEGF-C expression,
      and low E-cadherin expression in their tumors may benefit from close surveillance
      because they may have an increased risk of developing brain metastases.

PMID- 18720361
TI  - Irinotecan and uridine diphosphate glucuronosyltransferase 1A1 pharmacogenetics:
      to test or not to test, that is the question.
AB  - Pharmacogenetic research indicates a relationship between a polymorphism in the
      gene encoding uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and
      irinotecan inactivation, in that degradation of SN-38, the active metabolite of
      irinotecan, correlates inversely with the number of TA repeats in the TATA
      element of the UGT1A1 promoter region. Individuals who are homozygous for the
      UGT1A1*28 allele (7 repeats) may exhibit reduced degradation of SN-38 and
      increased probability of severe toxicities. Clinical study results, as reported
      in the literature, have not been uniform, however, in showing a relation between
      genotype and the development of toxicities. Even when correlations are
      statistically significant, confidence intervals are wide, rendering assessment of
      individual risk difficult at best. Irinotecan labeling recommends testing for the
      UGT1A1*28 allele and reducing irinotecan dosing in patients who are positive to
      reduce the likelihood of dose-limiting neutropenia only, but not diarrhea.
      Importantly, both dose-limiting neutropenia and diarrhea are dependent on
      numerous known and unknown factors, such as the specific regimen used, duration
      of therapy, doses, cycle of treatment, and complexities of irinotecan
      pharmacodynamics and pharmacokinetics, including other key enzymes and drug
      transporters. Guidance on how to modify irinotecan dosing or how to incorporate
      the impact of multiple variables into clinical decision-making does not exist.
      Furthermore, pharmacogenomic test results at this time can only provide an
      estimate of risk for subsets of populations rather than a risk-benefit estimate
      for an individual. Consequently, these test results are supplementary to clinical
      judgment, which requires assessing multiple variables that contribute to
      phenotype to arrive at individual dosing decisions.

PMID- 18720362
TI  - Prognostic nomogram for sunitinib in patients with metastatic renal cell
      carcinoma.
AB  - BACKGROUND: In a randomized, phase 3 trial, sunitinib demonstrated superior
      efficacy over interferon-alfa as first-line therapy in patients with metastatic
      clear-cell renal cell carcinoma (RCC). On the basis of outcome data from that
      trial, the authors developed a nomogram for predicting the probability of 12
      month progression-free survival for patients who received sunitinib therapy.
      METHODS: Three-hundred seventy-five patients who received sunitinib in the phase
      3 trial were the subject of the current analysis. Nomogram pretreatment predictor
      variables included corrected serum calcium levels, the number of metastatic
      sites, hemoglobin levels, prior nephrectomy, the presence of lung and liver
      metastases, thrombocytosis, Eastern Cooperative Oncology Group performance
      status, time from diagnosis to treatment, and serum levels of alkaline
      phosphatase and lactate dehydrogenase. Investigator-assessed progression-free
      survival was the predicted outcome endpoint. Internal validation of the nomogram
      consisted of quantification of the discrimination with the concordance index and
      assessment of calibration. RESULTS: One-hundred seventy-four of 375 patients
      (46%) who received sunitinib achieved an objective response, and the median
      progression-free survival was 10.8 months (95% confidence interval, 10.6-12.6
      months). A nomogram for predicting the probability of 12-month progression-free
      survival for patients who received sunitinib therapy was constructed on the basis
      of a Cox regression model from 11 parameters that were determined before
      treatment. The concordance index was 0.633. CONCLUSIONS: A nomogram was developed
      from pretreatment clinical features to predict the probability of achieving 12
      month progression-free survival with sunitinib therapy for metastatic clear-cell
      RCC. The authors concluded that independent validation of the nomogram and
      additional studies to identify tumor-specific prognostic factors are warranted.

PMID- 18720363
TI  - Liposarcoma: outcome based on the Scandinavian Sarcoma Group register.
AB  - BACKGROUND: The aim was to study the clinicopathological characteristics,
      treatment, and outcome of liposarcoma in an unselected, population-based patient
      sample, and to establish whether treatment was according to the Scandinavian
      Sarcoma Group (SSG) treatment guidelines. METHODS: The SSG Pathology Board
      reviewed 319 liposarcoma cases reported between 1986 and 1998. After the review,
      237 patients without metastasis were analyzed for local recurrence rate in
      relation to surgical margins, radiotherapy, occurrence of metastasis, and
      survival. RESULTS: Seventy-eight percent of the patients were primarily operated
      on at a sarcoma center, 45% with wide margins. All patients operated on outside
      the center had nonwide margins. Low-grade lesions constituted 67% of cases.
      Despite nonwide surgery, only 58% of high-grade lesions were treated with
      postoperative radiotherapy. The risk of local recurrence after nonwide surgery,
      without irradiation, was 47% for high-grade lesions. The estimated 10-year, local
      recurrence-free and metastasis-free survival in the low-grade group was 87% and
      95%, respectively. In the high-grade group, it was 75% and 61%, respectively.
      Independent adverse prognostic factors for local recurrence were surgery outside
      a sarcoma center and histological type dedifferentiated liposarcoma. For
      metastases, they were old age, large tumor size, high grade, and histological
      type myxoid liposarcoma with a round cell component. Radiotherapy showed
      significant effect on local recurrence rate for the same grade and margin.
      CONCLUSIONS: Patients with liposarcoma should be treated at specialized centers.
      Postoperative radiotherapy decreases the local recurrence rate. To maintain
      quality and provide support for further trials, reporting to quality registers is
      crucial.

PMID- 18720364
TI  - Combination of 5-azacytidine and thalidomide for the treatment of myelodysplastic
      syndromes and acute myeloid leukemia.
AB  - BACKGROUND: The treatment of myelodysplastic syndromes (MDS) remains a challenge
      to the clinician despite recent advances. Many patients will either not respond
      or will have only limited and/or brief responses to single-agent therapy.
      Eventually, 30% of patients with MDS will progress and develop acute myeloid
      leukemia (AML). New strategies are needed for these patients. METHODS: 5
      Azacytidine (AZA) and thalidomide were administered to 40 patients with MDS or
      AML. AZA was given at a dose of 75 mg/m2 subcutaneously for 5 of 28 days together
      with thalidomide starting at a dose of 50 mg per day and increasing to 100 mg
      per. Six patients had refractory anemia (RA), 2 patients had RA with ringed
      sideroblasts, 10 patients had RA with excess blasts (RAEB), 1 patient had RAEB in
      transformation, 4 patients had chronic myelomonocytic leukemia, 1 patient had
      chronic idiopathic myelofibrosis, and 16 patients had AML. Thirty-six patients
      were evaluable for outcome. RESULTS: A hematologic improvement (HI) was observed
      in 15 of 36 patients (42%), stable disease was observed in 5 of 36 patients
      (14%), and 10 of 36 patients (28%) had disease progression. Six patients
      experienced complete remission (CR), 2 patients experienced an erythroid HI (HI
      E), 1 patient experience an absolute neutrophil count HI (HI-ANC), 5 patients
      experienced a platelet HI (HI-P), and 7 patients had bilineage HI (HI-P and HI
      ANC or an HI-E and HI-ANC). It was noteworthy that 9 of 14 patients with AML had
      a history of prior MDS, 2 of 9 patients achieved a CR, 4 of 9 patients had HI (HI
      E and bilineage HI), and 1 patient had stable disease and was continuing
      treatment. DNA microarray analysis of 8 responders and 4 nonresponders revealed
      that the genes associated with cellular proliferation had higher expression
      levels in nonresponders. CONCLUSIONS: The current findings indicated that a
      combination of low-dose AZA and thalidomide was well tolerated and was effective
      therapy for the treatment of patients with MDS and AML arising from prior MDS.

PMID- 18720365
TI  - Morning cortisol Levels in preschool-aged foster children: differential effects
      of maltreatment type.
AB  - Maltreated foster children are subjected to a range of early adverse experiences,
      including neglect, abuse, and multiple caregiver disruptions. Research suggests
      that such disturbances alter the development and subsequent functioning of the
      hypothalamic-pituitary-adrenocortical system. The current study was designed to
      investigate morning cortisol levels in 117 foster children and 60 low-income,
      nonmaltreated children. Maltreatment and foster care placement experiences were
      coded from official records. Analyses revealed that the foster children were
      significantly more likely than the nonmaltreated children to have low morning
      cortisol levels. Additionally, specific maltreatment experiences were
      significantly associated with the foster children's morning cortisol levels.
      Foster children with low morning cortisol levels experienced more severe physical
      neglect than the other foster children. In contrast, foster children with high
      morning cortisol levels experienced more severe emotional maltreatment. These
      results suggest that specific early adverse experiences have differential effects
      on the functioning of the hypothalamic-pituitary-adrenocortical system.

PMID- 18720367
TI  - Lymph nodes in gastric cancer.
AB  - Surgery is the only curative therapy for gastric cancer and controversy still
      exist on the extend of surgery. As the lymphatic distribution of stomach is very
      complex, the determination of the actual lymph node involvement is important for
      making the decision in order to avoid complications. Sentinel node navigation
      surgery has recently been introduced in gastrointestinal tract cancer. Present
      article reviews the detection techniques of lymph nodes and significance of
      lymphadenectomies in gastric cancer.

PMID- 18720369
TI  - Introduction to the supplement on cancer in the American Indian and Alaska Native
      populations in the United States.
AB  - The collection of papers in this Supplement combines cancer incidence data from
      the National Program of Cancer Registries and the Surveillance, Epidemiology, and
      End Results program, enhanced by record linkages and geographic factors, to
      provide a comprehensive description of the cancer burden in the American
      Indian/Alaska Native population in the United States. Cancer incidence rates
      among this population varied widely, sometimes more than 5-fold, by geographic
      region.

PMID- 18720370
TI  - Investigations of a simulated geomagnetic field experienced by the International
      Space Station on attentional performance.
AB  - We have previously reported that the exposure to an abnormal magnetic field
      simulating the one encountered by the International Space Station (ISS) orbiting
      around the Earth may enhance autonomic response to emotional stimuli. Here we
      report the results of the second part of that study which tested whether this
      field also affects cognitive functions. Twenty-four volunteers participated in
      the study, 12 exposed to the natural geomagnetic field and 12 to the magnetic
      field encountered by ISS. The test protocol consisted of a set of eight tests
      chosen from a computerized test battery for the assessment of attentional
      performance. The duration of exposure was 90 min. No effect of exposure to ISS
      magnetic field was observed on attentional performance.

PMID- 18720371
TI  - Cancer in American Indian and Alaska Native populations continues to threaten an
      aging population : the need for tribal, state, and federal action.

PMID- 18720372
TI  - Methods for improving cancer surveillance data in American Indian and Alaska
      Native populations.
AB  - BACKGROUND: The misclassification of race decreases the accuracy of cancer
      incidence data for American Indians and Alaska Natives (AI/ANs) in some central
      cancer registries. This article describes the data sources and methods that were
      used to address this misclassification and to produce the cancer statistics used
      by most of the articles in this supplement. METHODS: Records from United States
      cancer registries were linked with Indian Health Service (IHS) records to
      identify AI/AN cases that were misclassified as non-AI/AN. Data were available
      from 47 registries that linked their data with IHS, met quality criteria, and
      agreed to participate. Analyses focused on cases among AI/AN residents in IHS
      Contract Health Service Delivery Area (CHSDA) counties in 33 states. Cancer
      incidence and stage data were compiled for non-Hispanic whites (NHWs) and AI/ANs
      across 6 IHS regions of the United States for 1999 through 2004. RESULTS:
      Misclassification of AI/AN race as nonnative in central cancer registries ranged
      from 85 individuals in Alaska (3.4%) to 5297 individuals in the Southern Plains
      (44.5%). Cancer incidence rates among AI/ANs for all cancers combined were lower
      than for NHWs, but incidence rates varied by geographic region for AI/ANs.
      Restricting the rate calculations to CHSDA counties generally resulted in higher
      rates than those obtained for all counties combined. CONCLUSIONS: The
      classification of race for AI/AN cases in cancer registries can be improved by
      linking records to the IHS and stratifying by CHSDA counties. Cancer in the AI/AN
      population is clarified further by describing incidence rates by geographic
      region. Improved cancer surveillance data for AI/AN communities should aid in the
      planning, implementation, and evaluation of more effective cancer control and
      should reduce health disparities in this population.

PMID- 18720373
TI  - Activation loop phosphorylation of the atypical MAP kinases ERK3 and ERK4 is
      required for binding, activation and cytoplasmic relocalization of MK5.
AB  - Mitogen-activated protein (MAP) kinases are typical examples of protein kinases
      whose enzymatic activity is mainly controlled by activation loop phosphorylation.
      The classical MAP kinases ERK1/ERK2, JNK, p38 and ERK5 all contain the conserved
      Thr-Xxx-Tyr motif in their activation loop that is dually phosphorylated by
      members of the MAP kinase kinases family. Much less is known about the regulation
      of the atypical MAP kinases ERK3 and ERK4. These kinases display structural
      features that distinguish them from other MAP kinases, notably the presence of a
      single phospho-acceptor site (Ser-Glu-Gly) in the activation loop. Here, we show
      that ERK3 and ERK4 are phosphorylated in their activation loop in vivo. This
      phosphorylation is exerted, at least in part, in trans by an upstream cellular
      kinase. Contrary to classical MAP kinases, activation loop phosphorylation of
      ERK3 and ERK4 is detected in resting cells and is not further stimulated by
      strong mitogenic or stress stimuli. However, phosphorylation can be modulated
      indirectly by interaction with the substrate MAP kinase-activated protein kinase
      5 (MK5). Importantly, we found that activation loop phosphorylation of ERK3 and
      ERK4 stimulates their intrinsic catalytic activity and is required for the
      formation of stable active complexes with MK5 and, consequently, for efficient
      cytoplasmic redistribution of ERK3/ERK4-MK5 complexes. Our results demonstrate
      the importance of activation loop phosphorylation in the regulation of ERK3/ERK4
      function and highlight differences in the regulation of atypical MAP kinases as
      compared to classical family members.

PMID- 18720374
TI  - Surveillance for health behaviors of American Indians and Alaska Natives-findings
      from the behavioral risk factor surveillance system, 2000-2006.
AB  - BACKGROUND: The authors compared estimates for cancer risk factors, use of cancer
      screening tests, health status indicators, and access to care for American
      Indians and Alaska Natives (AI/ANs) and non-Hispanic whites (NHWs) in the US and
      for AI/ANs in 6 Indian Health Service regions. METHODS: Behavioral Risk Factor
      Surveillance System data were aggregated from the years 2000 through 2006 and
      were used to calculate weighted prevalence estimates by gender for key variables
      except demographic variables. RESULTS: Compared with NHWs, AI/ANs had lower
      prevalence estimates for income, educational attainment, insurance coverage, and
      access to personal healthcare providers. AI/ANs in Alaska and NHWs had similar
      estimates for diabetes (approximately 6%); however, the prevalence was nearly
      twice as high among AI/ANs in the other regions. The prevalence of obesity was
      higher for AI/ANs (29.6%) than for NHWs (20.9%). The prevalence of binge drinking
      was higher among AI/AN males (24.9%) than among AI/AN females (8.5%). Heavy
      drinking was more prevalent among NHW females (5.3%) than among AI/AN females
      (3.5%). AI/ANs were more likely to be current smokers (31.1%) than NHWs (22.8%).
      The prevalence of AI/ANs who never smoked ranged from 31.5% in Alaska to 56.9% in
      the Southwest. In 5 of the 6 regions, AI/AN females had lower prevalence
      estimates of both Papanicolaou and mammography testing than NHW females. The use
      of colorectal cancer screening tests was more common among NHWs (53.8%) than
      among AI/ANs (44%). CONCLUSIONS: Although cancer health disparities persist among
      AI/ANs, the current analysis indicated that variation in the prevalence of their
      chronic disease risk factors may be obscured when national data are not examined
      by smaller geographic areas such as regions.

PMID- 18720375
TI  - Cancer among American Indians and Alaska Natives in the United States, 1999-2004.
AB  - BACKGROUND: Cancer incidence rates vary among American Indian and Alaska Native
      (AI/AN) populations and often differ from rates among non-Hispanic whites (NHWs).
      However, the misclassification of race for AI/AN cancer cases in central cancer
      registries may have led to underestimates of the AI/AN cancer burden in previous
      reports. METHODS: Cases diagnosed during 1999 through 2004 were identified from
      population-based cancer registries in the United States. Age-adjusted rates were
      calculated for the 25 most common sites for AI/ANs and NHWs. To minimize the
      misclassification of race, cancer registry records were linked with patient
      registration files from the Indian Health Service (IHS). Analyses were restricted
      to Contract Health Service Delivery Area (CHSDA) counties and were stratified by
      IHS region. RESULTS: In CHSDA counties, cancer incidence rates among AI/ANs
      varied widely by region, whereas rates among NHWs did not. For all cancer sites
      combined, AI/AN rates were higher than NHW rates among both males and females in
      the Northern and Southern Plains, and among Alaska Native Females; AI/AN rates
      were lower than NHW rates in the Southwest, the Pacific Coast, and the East. Lung
      cancer and colorectal cancer rates for AI/ANs exceeded rates for NHWs in Alaska
      and the Northern Plains. Rates for stomach, gallbladder, kidney, and liver cancer
      were higher among AI/ANs than among NHWs overall, in Alaska, in the Plains
      regions, and in the Southwest. CONCLUSIONS: Regional differences in cancer
      incidence rates among AI/AN populations were not obvious from nationwide data and
      highlighted opportunities for cancer control and prevention. It is unlikely that
      such differences are explained by race misclassification.

PMID- 18720376
TI  - Prostate cancer incidence among American Indian and Alaska Native men, US, 1999
      2004.
AB  - BACKGROUND: American Indian and Alaska Native (AI/AN) men experience lower
      incidence of prostate cancer than other race/ethnic populations in the US, but
      racial misclassification of AI/AN men threatens the validity of these estimates.
      To the authors' knowledge, little is known concerning prostate-specific antigen
      (PSA) testing in AI/AN men. METHODS: The authors linked cancer registry data with
      Indian Health Service enrollment records to improve race classification. Analyses
      comparing cancer incidence rates and stage at diagnosis for AI/AN and non
      Hispanic white (NHW) men for 6 geographic regions focused on counties known to
      have less race misclassification. The authors also used Behavioral Risk Factors
      Surveillance System data to characterize PSA testing in AI/AN men. RESULTS:
      Prostate cancer incidence rates were generally lower in AI/AN than in NHW men for
      all regions combined (rate ratio of 0.68). However, regional variation was noted
      among AI/AN men, with incidence rates (per 100,000 population) ranging from 65.7
      in the Southwest to 174.5 on the Northern Plains. The rate of distant stage
      disease was somewhat higher among AI/AN (7.8) than NHW (6.2) men. Nationally,
      AI/AN men were less likely than NHW men to have undergone recent PSA testing
      (48.4% vs 58.0%), with prominent regional variation in screening rates noted.
      CONCLUSIONS: Prostate cancer incidence rates and the proportion of men with
      recent PSA testing were lower for AI/AN men than for NHW men. However, incident
      rates and rate of distant stage varied by region more for AI/AN than for NHW.
      Further research is needed among AI/AN men to evaluate strategies for better
      understanding the causes of the regional variation in prostate cancer incidence.

PMID- 18720377
TI  - Cancers of the urinary tract among American Indians and Alaska Natives in the
      United States, 1999-2004.
AB  - BACKGROUND: Assessment of the kidney parenchyma ("kidney") and urinary bladder
      ("bladder") cancer burden among American Indians and Alaska Natives (AI/AN) has
      been limited. Using a database with improved classification for AI/AN, the
      authors described patterns of these 2 cancers among AI/AN and non-Hispanic whites
      (NHW) in the United States. METHODS: Cases diagnosed during 1999 to 2004 were
      identified through National Program of Cancer Registries and the Surveillance,
      Epidemiology and End Results program and linked to the Indian Health Service
      (IHS) registration records. Age-adjusted incidence rates, rate ratios (RR),
      annual percent change, and stage at diagnosis were stratified by IHS Contract
      Health Service Delivery Area (CHSDA) counties to adjust for misclassification.
      RESULTS: Kidney cancer incidence among AI/AN in CHSDA counties exceeded that
      among NHW (RR, 1.51; 95% confidence interval [CI], 1.42-1.61), and was highest
      among AI/AN in the Northern Plains, Southern Plains, Alaska, and Southwest.
      Average annual increases were highest among AI/AN (5.9%) and NHW (5.9%) males
      aged 20 to 49 years, although statistically significant only among NHW.
      Conversely, bladder cancer incidence was significantly lower among AI/AN than NHW
      (RR, 0.40; 95% CI, 0.37-0.44). For both sites, AI/AN were significantly less
      likely to be diagnosed at an earlier stage than NHW. CONCLUSIONS: AI/AN have
      about 50% greater risk of kidney cancer and half the risk of bladder cancer than
      NHW. Although reasons for these enigmatic patterns are not known, sustained
      primary prevention efforts through tobacco cessation and obesity prevention are
      warranted.

PMID- 18720378
TI  - Gastric cancer among American Indians and Alaska Natives in the United States,
      1999-2004.
AB  - BACKGROUND: Gastric cancer incidence rates for American Indians and Alaska
      Natives (AI/ANs) historically have exceeded those for non-Hispanic whites (NHWs).
      Previous reports may have underestimated the true burden of gastric cancer in
      AI/AN populations because of misclassification of AI/AN race in cancer
      registries. METHODS: Population-based cancer registry data from 1999 through 2004
      were used to describe gastric cancer incidence in AI/ANs and NHWs in the US. To
      address misclassification of race, registry data were linked with Indian Health
      Service administrative records, and analyses were restricted to residents of
      Contract Health Service Delivery Areas (CHSDA). Disease patterns were assessed
      for 6 geographic regions and for all regions combined. Rates were expressed per
      100,000 population and were age-adjusted to the 2000 US standard population.
      RESULTS: In CHSDA counties, gastric cancer incidence rates for AI/ANs were higher
      than the rates for NHWs across most regions. For both sexes combined, AI/AN rates
      ranged from 6.1 in the East region to 24.5 in Alaska; there was relatively little
      regional variation in NHW rates. Most patients with gastric cancer were diagnosed
      with late-stage disease, regardless of race, age, or sex. In some regions, cancer
      rates in the central/distal portions of the stomach were higher among AI/ANs than
      among NHWs, whereas rates in the proximal stomach were similar between the 2
      populations. CONCLUSIONS: AI/ANs are generally at greater risk for gastric cancer
      than NHWs. Relatively high rates of cancer in the central/distal portions of the
      stomach among AI/ANs in some geographic regions may indicate a disproportional
      burden of Helicobacter pylori-associated disease.

PMID- 18720379
TI  - Regional differences in cervical cancer incidence among American Indians and
      Alaska Natives, 1999-2004.
AB  - BACKGROUND: Reports from limited geographic regions indicate higher rates of
      cervical cancer incidence in American Indian and Alaska Native (AI/AN) women than
      in women of other races. However, accurate determinations of cervical cancer
      incidence in AI/AN women have been hampered by racial misclassification in
      central cancer registries. METHODS: The authors linked data from cancer
      registries participating in the National Program of Cancer Registries (NPCR) and
      the Surveillance, Epidemiology, and End Results (SEER) Program with Indian Health
      Service (IHS) enrollment records to improve identification of AI/AN race. NPCR
      and SEER data were combined to estimate annualized age-adjusted rates (expressed
      per 100,000 persons) for the diagnosis years 1999 to 2004. Analyses focused on
      counties known to have less racial misclassification, and results were stratified
      by IHS Region. Approximately 56% of AI/ANs in the US reside in these counties.
      The authors examined overall and age-specific incidence rates and stage at
      diagnosis for AI/AN women compared with non-Hispanic white (NHW) women. RESULTS:
      Invasive cervical cancer incidence rates among AI/AN women varied nearly 2-fold
      across IHS regions, with the highest rates reported in the Southern Plains (14.1)
      and Northern Plains (12.5); the lowest rates were in the Eastern region and the
      Pacific Coast. Overall, AI/AN women had higher rates of cervical cancer than NHW
      women and were more likely to be diagnosed with later stage disease. CONCLUSIONS:
      The wide regional variation of invasive cervical cancer incidence indicates an
      important need for health services research regarding cervical cancer screening
      and prevention education as well as policy development regarding human
      papillomavirus vaccine use, particularly in the regions with high incidence
      rates. Cancer 2008;113(5 suppl):1234-43. Published 2008 by the American Cancer
      Society.

PMID- 18720380
TI  - Primary liver cancer incidence among American Indians and Alaska Natives, US,
      1999-2004.
AB  - BACKGROUND: American Indians and Alaska Natives (AI/AN) experience higher
      morbidity and mortality from primary liver cancer than other United States (US)
      populations, but racial misclassification in medical records results in
      underestimates of disease burden. METHODS: To reduce misclassification, National
      Program of Cancer Registries and Surveillance, Epidemiology, and End Results data
      were linked with Indian Health Service (IHS) enrollment records to compare
      primary liver cancer incidence and stage at diagnosis between AI/AN and non
      Hispanic whites (NHW) living within the regionalized IHS Contract Health Service
      Delivery Area counties. Incidence rates are expressed per 100,000 persons and age
      adjusted by 19 age groups to the 2000 US standard population. RESULTS: Overall,
      AI/AN have a higher proportion of hepatocellular carcinoma compared with NHW,
      77.8% versus 66.7%. Liver cancer incidence rates among AI/AN males and females
      were higher than those among NHW males and females for all regions except for the
      East. Among males, rates ranged from 7.3 (95% confidence interval [CI], 3.8-12.6)
      in the East to 17.2 (95% CI, 10.4-26.3) in Alaska. Among females, rates ranged
      from 3.8 (95% CI, 1.4-8.2) in the East to 6.9 (95% CI, 3.6-11.6) in Alaska. The
      AI/AN rates for all regions were consistently higher than the NHW rates at every
      age. An increasing trend among AI/AN was suggested but did not achieve
      statistical significance. CONCLUSIONS: Reducing racial misclassification revealed
      higher disparities in primary liver cancer incidence between NHW and AI/AN
      populations than previously reported. Further description of the reasons for
      regional differences in this disparity is needed, as are programs to reduce risk
      factors and to diagnose primary liver cancer at earlier, more treatable stages.

PMID- 18720381
TI  - Incidence of cancers of the oral cavity and pharynx among American Indians and
      Alaska Natives, 1999-2004.
AB  - BACKGROUND: Previous studies identified disparities in incidence rates of cancers
      of the oral cavity and pharynx between American Indians/Alaska Natives (AI/AN)
      and non-Hispanic whites (NHW) and differences between various AI/AN populations.
      Reporting among AI/AN has been hampered by: 1) heterogeneity among various
      anatomic sites of oral cavity and pharyngeal cancers obscuring unique patterns of
      individual anatomic sites; 2) race misclassification and underreporting of AI/AN;
      and 3) sparseness of data needed to identify regional variations. METHODS: To
      improve race classification of AI/AN, data from US central cancer registries were
      linked with Indian Health Service (IHS) records. AI/AN incidence data from 1999
      to 2004 were stratified by sex, age, stage at diagnosis, and anatomic subsite for
      6 IHS geographic regions and compared with NHW populations. RESULTS: For all oral
      cavity and pharynx cancers combined, among residents of Contract Health Service
      Delivery Area counties, AI/AN overall had significantly lower incidence rates
      than NHW (8.5 vs 11.0). However, AI/AN rates were significantly higher in the
      Northern Plains (13.9 vs 10.5) and Alaska (16.3 vs 10.6), significantly lower in
      the Pacific Coast (7.7 vs 11.6) and Southwest (3.3 vs 10.4), and similar in the
      Southern Plains (11.4). Overall AI/AN males had higher incidence rates than AI/AN
      women. Nasopharyngeal cancer was more frequent (1.1AI/AN vs 0.4 NHW), and tongue
      cancer less frequent (1.6 AI/AN vs 2.9 NHW) in AI/AN than NHW populations;
      however, rates varied by region. Stage distribution was modestly less favorable
      for AI/AN compared with NHW populations. CONCLUSIONS: Variation by region,
      anatomic site, and sex indicates a need for research into etiologic factors and
      attention to regional risk factor profiles when planning cancer control programs.

PMID- 18720382
TI  - Gallbladder cancer incidence among American Indians and Alaska Natives, US, 1999
      2004.
AB  - BACKGROUND: Gallbladder cancer (GBC) is rare; however, it disproportionately
      affects the American Indian and Alaska Natives (AI/AN) population. The purpose of
      the study was to characterize GBC among AI/AN in the US population. METHODS:
      Cases of GBC diagnosed between 1999 and 2004 and collected by state-based cancer
      registries were included. Registry records were linked with Indian Health Service
      (IHS) administration records to decrease race misclassification of AI/AN. GBC
      rates and/or percent distributions for AI/AN and non-Hispanic whites (NHW) were
      calculated by sex, IHS region, age, and stage for all US counties and IHS
      Contract Health Service Delivery Area (CHSDA) counties, in which approximately
      56% of US AI/AN individuals reside. RESULTS: In CHSDA counties, the GBC incidence
      rate among AI/AN was 3.3 per 100,000, which was significantly higher than that
      among NHW (P < .05). Rates varied widely among IHS regions and ranged from 1.5 in
      the East to 5.5 in Alaska. Rates were higher among AI/AN females than males in
      all regions, except the Northern Plains. Higher percentages of GBC were diagnosed
      among AI/AN aged <65 years compared with NHW. GBC was most often diagnosed at the
      regional stage among AI/AN, whereas GBC was most often diagnosed at regional or
      distant stages among NHW. CONCLUSIONS: To the authors' knowledge to date, this is
      the most comprehensive study of GBC incidence among AI/AN in the US. The accurate
      characterization of GBC in this population could help inform the development of
      interventions aimed at reducing morbidity and mortality from this disease.

PMID- 18720383
TI  - Subchronic racemic gamma vinyl-GABA produces weight loss in Sprague Dawley and
      Zucker fatty rats.
AB  - Given the growing obesity epidemic, pressure to develop an effective
      pharmacologic treatment is mounting. Following the completion of a randomized,
      double-blind, placebo controlled trial as well as two small open label trials,
      gamma vinyl-GABA (GVG) has been shown to be safe and effective for treating
      cocaine and/or methamphetamine dependence. In an extension of these findings, the
      present study examined whether GVG could produce weight loss in adolescent as
      well as genetically obese animals. Specifically, adolescent Sprague Dawley and
      adolescent and adult Zucker fatty rats received GVG at various doses (75-300
      mg/kg, i.p., racemic) for treatment periods lasting no longer than 14 consecutive
      days. GVG produced significant weight loss in a dose dependent fashion in all
      groups. These effects were marked, as average decreases of 12-20% of original
      body weight were observed. These findings suggest that GVG may be useful as a
      treatment for obesity. Further, that these results occurred in genetically obese
      animals offers the possibility that GVG may even help manage severe obesity
      resulting from binge-eating, a disorder involving food consumption in a pattern
      similar to the compulsive drug-seeking behavior observed in cocaine and
      methamphetamine dependent subjects.

PMID- 18720384
TI  - Oversulfated chondroitin sulfate-E binds to BMP-4 and enhances osteoblast
      differentiation.
AB  - Small leucine-rich proteoglycans, such as biglycan, and their side chain sulfated
      glycosaminoglycans (GAGs), have been suggested to be involved in bone formation
      and mineralization processes. The present study was designed to investigate
      whether chondroitin sulfate (CS), one of the GAG, and its oversulfated structures
      coupled with bone morphogenetic protein-4 (BMP-4) alter the differentiation and
      subsequent mineralization of MC3T3-E1 osteoblastic cells. CS-E, one of the
      oversulfated CS structure, enhanced cell growth, alkaline phosphatase (ALP)
      activity, collagen deposition, and mineralization whereas heparin enhanced only
      ALP activity and mineralization. As well as CS-E, CS-H, and CPS also enhanced the
      mineralization of the cells. CS-E enhanced the mineralization of the cells by
      interacting with protein in the conditioned medium. CS-E induced mineralization
      was significantly inhibited by an antibody against BMP-4. The addition of
      exogenous BMP-4 further increased the capacity of CS-E to enhance mineralization.
      Fluorescence correlation spectroscopy method using fluoresceinamine-labeled GAG
      revealed that the oversulfated GAGs have a high affinity for BMP-4. The
      disaccharide analysis of the cells indicated that MC3T3-E1 cells are capable of
      producing oversulfated structures of CS by themselves. The lack of CS from the
      cells after chondroitinase treatment resulted in the inhibition of
      mineralization. These results in the present study indicate that oversulfated CS,
      which possesses 4,6-disulfates in N-acetyl-galactosamine, binds to BMP-4 and
      promotes osteoblast differentiation and subsequent mineralization.

PMID- 18720385
TI  - The angiopoietin-2 gene of endothelial cells is up-regulated in hypoxia by a HIF
      binding site located in its first intron and by the central factors GATA-2 and
      Ets-1.
AB  - Angiopoietins are ligands of the endothelial cell tyrosine kinase receptor Tie2.
      Angiopoietin-1 (Ang-1) is widely expressed in human normal adult tissues and
      promotes blood vessel maturation and stabilization by inducing Tie2 receptor
      phosphorylation. In contrast, the antagonistic ligand Angiopoietin-2 (Ang-2) is
      up-regulated by hypoxia, expressed only at sites of vascular remodeling and plays
      a crucial role in destabilizing vessels for normal or pathological angiogenesis.
      Ang-2 expression is tightly regulated at transcriptional and post-transcriptional
      levels. To characterize the regulatory sequences of the human Ang-2 gene we
      cloned a fragment of around 8.5 kb upstream of the Ang-2 coding sequence and
      analyzed the luciferase reporter activity of constructs of various lengths in
      endothelial and non-endothelial cells. We isolated a minimal promoter sequence
      sufficient to promote significant Ang-2 non-cell type specific transcription.
      Moreover, we identified sequences conferring endothelial specificity. Indeed,
      sequence analysis of the fragment revealed the presence of several potential
      binding sites for specific endothelial regulatory factors like GATA or Ets. Using
      GATA-2 and Ets-1 co-transfection and overexpression assay, we showed that these
      two factors are able to induce Ang-2 promoter activation. We also show that
      hypoxic regulation of Ang-2 is HIF-dependent and demonstrate that HIF-1alpha
      binds in human microvascular endothelial cells (HMVEC) to an evolutionary
      conserved Hypoxia-Responsive Element (HRE) located in the first intron of the Ang
      2 gene. In conclusion, our study provides new elements in favor of HIF
      involvement in Ang-2 hypoxic regulation and identifies Ets-1 and particularly
      GATA-2 as central factors in endothelial specific Ang-2 expression.

PMID- 18720386
TI  - Cancer in American Indian and Alaska Native young adults (ages 20-44 years): US,
      1999-2004.
AB  - BACKGROUND: An examination of cancer incidence patterns in American Indians and
      Alaska Native (AI/AN) young adults may provide insight into their present and
      future cancer burden. METHODS: To reduce racial misclassification, incidence data
      were linked with the Indian Health Service (IHS) patient services database. Age
      adjusted cancer incidence rates per 100,000 (AAR) and corresponding rate ratios
      (RR) for young adults (ages 20-44 years) were compared across IHS regions and for
      selected cancers within Contract Health Service Delivery Area counties by race
      (AI/AN vs non-Hispanic whites [NHW]) and sex. RESULTS: The all-sites cancer
      incidence rate was lower for AI/ANs (AAR of 83.8) than for NHWs (AAR of 111.2)
      (RR of 0.75) but varied by IHS regions. Among the leading cancers in AI/AN
      females the risk was elevated for stomach (RR of 3.22), colorectal (RR of 1.30),
      uterine (RR of 1.61), and kidney (RR of 1.39) cancers and was lower for breast
      (RR of 0.70) and thyroid (RR of 0.71) cancers. Among AI/AN young adult males the
      risk was elevated for stomach (RR of 2.62), liver (RR of 1.89), and kidney (RR of
      1.59) cancers and lower for testicular germ cell cancer (RR of 0.64) and lymphoma
      (RR of 0.60). The risk for these and other cancers varied across IHS regions.
      CONCLUSIONS: Many of the cancer patterns that characterize the AI/AN population
      overall are apparent among young adults. Compared with NHW young adults, the
      overall cancer burden among AI/AN young adults was lower but varied for selected
      cancers and across IHS regions. Cancer control and research strategies are needed
      to address the unique genetic, social, cultural, and lifestyle aspects of AI/AN
      young adults.

PMID- 18720387
TI  - Lung cancer incidence among American Indians and Alaska Natives in the United
      States, 1999-2004.
AB  - BACKGROUND: Lung cancer incidence rates among American Indians and Alaska Natives
      (AI/ANs) in the United States have not been described well, primarily because of
      race misclassification and, until the 1990s, incomplete coverage of their
      population by cancer registries. Smoking, the predominant cause of lung cancer,
      is particularly prevalent among this population. METHODS: Data from the National
      Program of Cancer Registries and the Surveillance, Epidemiology, and End Results
      Program were combined to estimate age-adjusted incidence rates of lung cancer
      during 1999 through 2004. Cases were linked to Indian Health Service (IHS)
      registration databases to identify AI/ANs whose race may have been misclassified.
      Age-adjusted rates were calculated for Contract Health Service Delivery Area
      (CHSDA) counties and for all counties by IHS region, and comparisons were made
      between AI/ANs and non-Hispanic whites (NHWs). RESULTS: Among populations living
      in CHSDA counties, NHWs overall had higher rates of lung cancer than AI/ANs.
      However, the rates (per 100,000 population) among AI/ANs varied substantially
      between IHS regions from 14.9 (Southwest) to 87.1 (Southern Plains), 93.2
      (Alaska), and 104.3 (Northern Plains). Approximately 41.6% of AI/AN lung cancer
      cases were diagnosed before age 65 years compared with approximately 29.8% of NHW
      lung cancer cases. The overall percentage stage distribution was not different
      between AI/ANs and NHWs. Squamous cell carcinomas were slightly more common and
      adenocarcinomas were less common among AI/ANs than among NHWs. Lung cancer rates
      were not decreasing for AI/ANs as they were for NHWs. CONCLUSIONS: Data from this
      study clarified the need for culturally appropriate tobacco prevention and
      control policies and resources for AI/ANs in all regions, and especially in the
      Plains and Alaska.

PMID- 18720388
TI  - Regional differences in colorectal cancer incidence, stage, and subsite among
      American Indians and Alaska Natives, 1999-2004.
AB  - BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer morbidity and
      mortality for American Indians and Alaska Natives (AI/ANs), but misclassification
      of race causes underestimates of disease burden. METHODS: The authors compared
      regional differences in CRC incidence, stage at diagnosis, and anatomic
      distribution between AI/ANs and non-Hispanic whites (NHWs). To reduce
      misclassification, data from the National Program of Cancer Registries; the
      Surveillance, Epidemiology, and End Results Program; and the Indian Health
      Service (IHS) were linked. The analysis was limited to the 56% of AI/AN who live
      in IHS Contract Health Service Delivery Areas. RESULTS: From 1999 to 2004, the
      overall incidence rate (per 100,000 persons per year) of CRC was 9% lower in the
      AI/AN population (46.3) than in the NHW population (50.8). However, AI/AN CRC
      incidence rates varied nearly 5-fold regionally, from 21 in the Southwest to
      102.6 in Alaska. Compared with NHW rates, AI/AN rates were significantly higher
      in Alaska (rate ratio [RR], 2.03), the Northern Plains (RR, 1.39), and the
      Southern Plains (RR, 1.16) but were lower in the Pacific Coast (RR, 0.80), the
      East (RR, 0.65), and the Southwest (RR, 0.45). AI/ANs were diagnosed more often
      with advanced CRC than with localized CRC (RR, 1.92) compared with NHWs (RR,
      1.48). Females more often had proximal CRC among both the AI/AN population
      (females, 40.1%; males, 33.5%) and the NHW population (females, 50.1%; males,
      40.3%), although AI/ANs had a higher proportion of distal cancers overall.
      CONCLUSIONS: CRC incidence rates in AI/AN populations varied dramatically between
      regions. Efforts are needed to make CRC screening a priority, overcome barriers
      to endoscopic screening, and to engage AI/AN communities in culturally
      appropriate ways to participate in prevention and early detection programs.

PMID- 18720389
TI  - Breast cancer incidence among American Indian and Alaska Native women: US, 1999
      2004.
AB  - BACKGROUND: Breast cancer is a leading cause of cancer morbidity and mortality
      among American Indian and Alaska Native (AI/AN) women. Although published studies
      have suggested that breast cancer rates among AI/AN women are lower than those
      among other racial and ethnic populations, accurate determinations of the breast
      cancer burden have been hampered by misclassification of AI/AN race. METHODS:
      Cancer incidence data from the National Program of Cancer Registries and the
      Surveillance, Epidemiology, and End Results Program were combined to estimate age
      adjusted rates for the diagnosis years 1999 through 2004. Several steps were
      taken to reduce the misclassification of AI/AN race: linking cases to Indian
      Health Service (IHS) patient services database, restricting analyses to Contract
      Health Service Delivery Area counties, and stratifying results by IHS region.
      RESULTS: Breast cancer incidence rates among AI/AN women varied nearly 3-fold
      across IHS regions. The highest rates were in Alaska (134.8) and the Plains
      (Northern, 115.9; Southern, 115.7), and the lowest rates were in the Southwest
      (50.8). The rate in Alaska was similar to the rate among non-Hispanic white (NHW)
      women in Alaska. Overall, AI/AN women had lower rates of breast cancer than NHW
      women, but AI/AN women were more likely to be diagnosed with late-stage disease.
      CONCLUSIONS: To the authors' knowledge, this report provides the most
      comprehensive breast cancer incidence data for AI/AN women to date. The wide
      regional variation indicates an important need for etiologic and health services
      research, and the large percentage of AI/AN women with late-stage disease demands
      innovative approaches for increasing access to screening.

PMID- 18720390
TI  - Trauma history characteristics and subsequent PTSD symptoms in motor vehicle
      accident victims.
AB  - The present study examined the relationship between trauma history
      characteristics (number and type of traumas, age at first trauma, and subjective
      responses to prior traumas) and the development of posttraumatic stress disorder
      (PTSD) symptoms following a motor vehicle accident (MVA). One hundred eighty
      eight adult MVA victims provided information about prior traumatization and were
      evaluated for PTSD symptoms 6 weeks and one year following the MVA. Results
      indicated that after controlling for demographics and depression, prior trauma
      history characteristics accounted for a small, but significant amount of the
      variance in PTSD symptoms. Distress from prior trauma and number of types of
      prior traumas were the most meaningful trauma history predictors. Results
      encourage further evaluation of trauma history as a multifaceted construct.

PMID- 18720391
TI  - Relationships among PTSD symptoms, social support, and support source in veterans
      with chronic PTSD.
AB  - The present study examined the temporal relationship between posttraumatic stress
      disorder (PTSD) and social support among 128 male veterans treated for chronic
      PTSD. Level of perceived interpersonal support and stressors were assessed at two
      time points (6 months apart) for four different potential sources of support:
      spouse, relatives, nonveteran friends, and veteran peers. Veteran peers provided
      relatively high perceived support and little interpersonal stress. Spouses were
      seen as both interpersonal resources and sources of interpersonal stress. More
      severe PTSD symptoms at Time 1 predicted greater erosion in perceived support
      from nonveteran friends, but not from relatives. Contrary to expectations,
      initial levels of perceived support and stressors did not predict the course of
      chronic PTSD symptoms.

PMID- 18720392
TI  - Nonnightmare distressed awakenings in veterans with posttraumatic stress
      disorder: response to prazosin.
AB  - Twenty-two veterans with posttraumatic stress disorder (PTSD) were assessed for
      trauma-related nightmares and nonnightmare distressed awakenings (NNDA) before
      and after treatment with the alpha-1 adrenoreceptor antagonist prazosin at an
      average bedtime dose of 9.6 mg/day. Ratings combining frequency and intensity
      dimensions of trauma-related nightmares decreased from 3.6 to 2.2, NNDA from 5.2
      to 2.1, and sleep difficulty from 7.2 to 4.1 per week. These results suggest that
      increased brain adrenergic activity may contribute to the pathophysiology of both
      trauma-related nightmares and NNDA in PTSD.

PMID- 18720393
TI  - Association of objective measures of trauma exposure from motor vehicle accidents
      and posttraumatic stress symptoms.
AB  - Associations of objective measures of trauma exposure with psychological sequelae
      following motor vehicle accidents (MVA) were examined in a Japanese population.
      Impact and injury severity of 93 MVA victims was assessed using on-the-scene in
      depth investigations measured by the Injury Severity Score (ISS), barrier
      equivalent speed (BES), and change in velocity during the impact (Delta-v).
      Results showed that ISS, BES, and Delta-v were not related to posttraumatic
      stress symptoms (PTSS) or psychiatric symptoms at 5 and 14 months after the MVA.
      Subjective measures (e.g., perceived life risk, persistent medical problems) were
      significantly related to psychological sequelae. These findings suggest that the
      objective measures of trauma exposure are not associated directly with PTSS or
      psychiatric symptoms after an MVA.

PMID- 18720394
TI  - Spanish and English versions of the PTSD Checklist-Civilian version (PCL-C):
      testing for differential item functioning.
AB  - Interpretation of ethnic differences in PTSD is predicated on demonstration that
      differences are not due to measurement bias. This is difficult when multiple
      languages are used in the assessment. This study used confirmatory factor
      analysis to examine possible differential item functioning (DIF) across English
      and Spanish versions of the PTSD Checklist-Civilian Version (PCL-C). Data were
      derived from two assessments of Hispanics (Ns = 304, 213), who were hospitalized
      with physical injuries. After correction for multiple testing, univariate tests
      revealed no statistically significant DIF effects; multivariate tests revealed
      some indication of DIF at the initial assessment only. This bias was inconsistent
      across waves and unlikely to be substantively consequential, indicating that the
      two versions of the PCL-C were generally equivalent.

PMID- 18720395
TI  - Does prior psychological health influence recall of military experiences? a
      prospective study.
AB  - In a prospective study, we evaluated pre- and postdeployment psychological health
      on recall of risk factors to assess recall bias. Measures of the General Health
      Questionnaire (GHQ), PTSD Checklist (PCL), and symptom clusters from the PCL were
      obtained from 681 UK military personnel along with information on traumatic and
      protective risk factors. Postdeployment psychological health was more important
      in explaining recall of traumatic experiences than predeployment psychological
      health. Predeployment intrusive cluster scores were highly associated with
      traumatic exposures. Postdeployment, but not predeployment GHQ showed small
      effects for most risk factors. With the exception of intrusive thoughts, there is
      insufficient evidence to suggest predeployment psychological status would be
      useful in correcting for recall bias in subsequent cross-sectional studies.

PMID- 18720396
TI  - Tonic immobility mediates the influence of peritraumatic fear and perceived
      inescapability on posttraumatic stress symptom severity among sexual assault
      survivors.
AB  - This study evaluated whether tonic immobility mediates the relations between
      perceived inescapability, peritraumatic fear, and posttraumatic stress disorder
      (PTSD) symptom severity among sexual assault survivors. Female undergraduates (N
      = 176) completed questionnaires assessing assault history, perceived
      inescapability, peritraumatic fear, tonic immobility, and PTSD symptoms. Results
      indicated that tonic immobility fully mediated relations between perceived
      inescapability and overall PTSD symptom severity, as well as reexperiencing and
      avoidance/numbing symptom clusters. Tonic immobility also fully mediated the
      relation between fear and reexperiencing symptoms, and partially mediated
      relations between fear and overall PTSD symptom severity, and avoidance/numbing
      symptoms. Results suggest that tonic immobility could be one path through which
      trauma survivors develop PTSD symptoms. Further study of tonic immobility may
      inform our ability to treat trauma victims.

PMID- 18720397
TI  - A prospective study of trait anger and PTSD symptoms in police.
AB  - It is unknown whether anger is a risk factor for the development of posttraumatic
      stress disorder ( PTSD) symptoms, arises as a consequence of PTSD, or both. Two
      hypotheses were tested in 180 police recruits: Greater trait anger during
      training will predict greater PTSD symptoms at one year; greater PTSD symptoms at
      one year will predict greater state anger at one year. Both hypotheses were
      confirmed, suggesting that trait anger is a risk factor for PTSD symptoms, but
      that PTSD symptoms are also associated with an increase of state anger. Increased
      anger is important not only because of the impact it has on individual distress
      and physical health, but also because of its potential public health impact.

PMID- 18720398
TI  - Corroborating evidence of posttraumatic growth.
AB  - Over the last decade, a healthy shift in the trauma literature has meant that
      published theory and research in the posttraumatic growth (PTG) domain has
      burgeoned, but the validity of the self-report questionnaires used to measure PTG
      has recently been criticized. Corroboration of these subjective reports by an
      observer would provide convergent validity. Therefore, this study's aim was to
      validate the Posttraumatic Growth Inventory (PTGI; Tedeschi & Calhoun, 1996).
      Sixty-one trauma survivors and 61 paired significant others completed the PTGI. A
      significant correlation was reported between the total PTGI scores of the trauma
      survivors and the corroborating significant others, supporting the use of the
      PTGI as an appropriate measure of positive posttrauma changes.

PMID- 18720399
TI  - Financial and social circumstances and the incidence and course of PTSD in
      Mississippi during the first two years after Hurricane Katrina.
AB  - Hurricane Katrina was the most devastating natural disaster to hit the United
      States in the past 75 years. The authors conducted interviews of 810 persons who
      were representative of adult residents living in the 23 southernmost counties of
      Mississippi before Hurricane Katrina. The prevalence of posttraumatic stress
      disorder (PTSD) since Hurricane Katrina was 22.5%. The determinants of PTSD were
      female gender, experience of hurricane-related financial loss, postdisaster
      stressors, low social support, and postdisaster traumatic events. Kaplan-Meier
      survival curves suggest that exposure to both hurricane-related traumatic events
      and to financial and social stressors influenced the duration of PTSD symptoms.
      Postdisaster interventions that aim to improve manipulable stressors after these
      events may influence the onset and course of PTSD.

PMID- 18720400
TI  - Localization of spindle checkpoint proteins in cells undergoing mitosis with
      unreplicated genomes.
AB  - CHO cells can be arrested with hydoxyurea at the beginning of the DNA synthesis
      phase of the cell cycle. Subsequent treatment with the xanthine, caffeine,
      induces cells to bypass the S-phase checkpoint and enter unscheduled mitosis
      [Schlegel and Pardee,1986, Science 232:1264-1266]. These treated cells build a
      normal spindle and distribute kinetochores, unattached to chromosomes, to their
      daughter cells [Brinkley et al.,1988, Nature 336:251-254; Zinkowski et al.,1991,
      J Cell Biol 113:1091-1110; Wise and Brinkley,1997, Cell Motil Cytoskeleton 36:291
      302; Balczon et al.,2003, Chromosoma 112:96-102]. To investigate how these cells
      distribute kinetochores to daughter cells, we analyzed the spindle checkpoint
      components, Mad2, CENP-E, and the 3F3 phosphoepitope, using immunofluorescence
      and digital microscopy. Even though the kinetochores were unpaired and DNA was
      fragmented, the tension, alignment, and motor components of the checkpoint were
      found to be present and localized as predicted in prometaphase and metaphase.
      This unusual mitosis proves that a cell can successfully localize checkpoint
      proteins and divide even when kinetochores are unpaired and fragmented.

PMID- 18720402
TI  - Postfamine stature and socioeconomic status in Ireland.
AB  - Previous research has documented socioeconomic stratification of secular trend in
      height in historical populations. Using data from 4,900 males and 1,430 females
      born between 1840 and 1910 collected as part of the Harvard Anthropological
      Survey of Ireland (1934-1936), this study examined the secular changes in
      postfamine Ireland using several socioeconomic variables, including: occupation,
      migration, education, siblings, birthplace, and occupation of father and mother's
      father. Correlations were also calculated between height and various historical
      economic indices. Significant differences in the height of Irish males were found
      by occupation, education, and socioeconomic status of father and maternal
      grandfather. Males employed in agriculture, or whose fathers or grandfathers were
      so employed, were significantly taller than other males. For the smaller female
      sample, only occupation and grandfather's socioeconomic status had a significant
      impact on height. An inverse correlation was also found between the British Cost
      of Living Index (BCL) and male heights. Our results suggest that availability of
      resources plays an important role in the overall nutritional status reflected in
      terminal adult height.

PMID- 18720401
TI  - Arp2 depletion inhibits sheet-like protrusions but not linear protrusions of
      fibroblasts and lymphocytes.
AB  - The Arp2/3 complex-mediated assembly and protrusion of a branched actin network
      at the leading edge occurs during cell migration, although some studies suggest
      it is not essential. In order to test the role of Arp2/3 complex in leading edge
      protrusion, Swiss 3T3 fibroblasts and Jurkat T cells were depleted of Arp2 and
      evaluated for defects in cell morphology and spreading efficiency. Arp2-depleted
      fibroblasts exhibit severe defects in formation of sheet-like protrusions at
      early time points of cell spreading, with sheet-like protrusions limited to
      regions along the length of linear protrusions. However, Arp2-depleted cells are
      able to spread fully after extended times. Similarly, Arp2-depleted Jurkat T
      lymphocytes exhibit defects in spreading on anti-CD3. Interphase Jurkats in
      suspension are covered with large ruffle structures, whereas mitotic Jurkats are
      covered by finger-like linear protrusions. Arp2-depleted Jurkats exhibit defects
      in ruffle assembly but not in assembly of mitotic linear protrusions. Similarly,
      Arp2-depletion has no effect on the highly dynamic linear protrusion of another
      suspended lymphocyte line. We conclude that Arp2/3 complex plays a significant
      role in assembly of sheet-like protrusions, especially during early stages of
      cell spreading, but is not required for assembly of a variety of linear actin
      based protrusions.

PMID- 18720403
TI  - Lack of association between serum antibodies of Chlamydia pneumoniae infection
      and the risk of lung cancer.

PMID- 18720404
TI  - Glycodelin reduces breast cancer xenograft growth in vivo.
AB  - Malignant growth is characterized by loss of cell differentiation, uncontrolled
      proliferation and resistance to apoptosis. Many tumor suppressor genes that
      protect cells against malignant transformation regulate cell differentiation.
      Here, we show for the first time that glycodelin, a differentiation-related
      protein, reduces breast cancer tumor growth in vivo. We found that glycodelin
      cDNA-transfected MCF-7 breast cancer cells showed a differentiated phenotype and
      produced smaller tumors in mouse mammary fat pads compared with control
      transfected cells. Glycodelin-induced differentiation was associated with reduced
      expression of oncogenes and increased expression of tumor suppressor genes. Our
      results suggest that glycodelin acts as a tumor suppressor in breast cancer. This
      may explain its reported association with a more favorable prognosis in some
      cancers.

PMID- 18720405
TI  - Morphological constancy in spelling: a comparison of children with dyslexia and
      typically developing children.
AB  - The spellings of many English words follow a principle of morphological
      constancy. For example, musician includes the c of music, even though the
      pronunciation of this letter changes. With other words, such as explanation and
      explain, the spellings of morphemes are not retained when affixes are added. We
      asked whether children with dyslexia use root morphemes to aid their spelling of
      morphologically complex words. If so, they should sometimes produce misspellings
      such as 'explaination' for explanation. Our results suggest that children with
      dyslexia adhere to the principle of morphological constancy to the same extent as
      typically developing younger children of the same spelling level. In this and
      other ways, the spellings of older dyslexic children are remarkably similar to
      those of typical younger children.

PMID- 18720407
TI  - Synaptic localization of GLT-1a in the rat somatic sensory cortex.
AB  - GLT-1a, the major glutamate transporter, plays an important role in both
      physiological and pathological conditions. Uncertainty regarding its localization
      in the cerebral cortex prompted us to re-examine its cellular and subcellular
      localization in the rat somatic sensory cortex. GLT-1a detection was sensitive to
      fixation; in optimal conditions approximately 25% of GLT-1a+ profiles were axon
      terminals. GLT-1a/VGLUT1 double-labeling and pre-embedding electron microscopy
      studies showed that approximately 50% of GLT-1a+ profiles were in the vicinity of
      asymmetric synapses. Using pre-embedding electron microscopy, we found that
      approximately 70% of GLT-1a located in the vicinity of asymmetric synapses was
      astrocytic and approximately 30% was neuronal. Post-embedding immunogold studies
      showed that the density of gold particles coding for GLT-1a was much higher in
      astrocytic processes than in axon terminals, and that in the latter they were
      never at the active zone. In both astrocytic processes and axon terminals most
      gold particles were localized in a membrane region extending for about 250 nm
      from active zone margin, with a peak at 140 nm for astrocytic processes and at 80
      for axon terminals. We conclude that, although GLT-1a is expressed by both
      astrocytes and axon terminals, astrocytic GLT-1a predominates at asymmetric
      synapses, and that the perisynaptic localization of GLT-1a in cortex is well
      suited to modulate Glu concentrations at the cleft and also to restrict Glu
      spillover.

PMID- 18720406
TI  - Oxidative DNA damage in osteoarthritic porcine articular cartilage.
AB  - Osteoarthritis (OA) is associated with increased levels of reactive oxygen
      species. This study investigated if increased oxidative DNA damage accumulates in
      OA articular cartilage compared with non-OA articular cartilage from pigs with
      spontaneous OA. Additionally, the ability of nitric oxide (NO) or peroxynitrite
      (ONOO(-)) induced DNA damage in non-OA chondrocytes to undergo endogenous repair
      was investigated. Porcine femoral condyles were graded for the stage of OA,
      macroscopically by the Collins Scale, and histologically by the modified Mankin
      Grade. Levels of DNA damage were determined in non-OA and OA cartilage, using the
      comet assay. For calibration, DNA damage was measured by exposing non-OA
      chondrocytes to 0-12 Gray (Gy) of X-ray irradiation. Non-OA articular
      chondrocytes were treated with 0-500 microM of NO donors (NOC-18 or SIN-1), and
      DNA damage assessed after treatment and 5 days recovery. A significant increase
      (P < 0.01) in oxidative DNA damage occurred in OA chondrocytes in joints with
      Mankin Grades 3 or greater, compared to non-OA chondrocytes. The percentage of
      nuclei containing DNA damage increased significantly (P < 0.001) from early to
      late grades of OA. An increase of approximately 0.65-1.7 breaks/1,000 kb of DNA
      occurred in OA, compared to non-OA nuclei. NOC-18 or SIN-1 caused significant DNA
      damage (P < 0.001) in non-OA chondrocytes that did not undergo full endogenous
      repair after 5 days (P < 0.05). Our data suggest significant levels of oxidative
      DNA damage occur in OA chondrocytes that accumulates with OA progression.
      Additionally, DNA damage induced by NO and ONOO(-) in non-OA chondrocytes does
      not undergo full endogenous repair.

PMID- 18720408
TI  - Combination therapy of lovastatin and rolipram provides neuroprotection and
      promotes neurorepair in inflammatory demyelination model of multiple sclerosis.
AB  - Drug combination therapies for central nervous system (CNS) demyelinating
      diseases including multiple sclerosis (MS) are gaining momentum over monotherapy.
      Over the past decade, both in vitro and in vivo studies established that statins
      (HMG-CoA reductase inhibitors) and rolipram (phosphodiesterase-4 inhibitor;
      blocks the degradation of intracellular cyclic AMP) can prevent the progression
      of MS in affected individuals via different mechanisms of action. In this study,
      we evaluated the effectiveness of lovastatin (LOV) and rolipram (RLP) in
      combination therapy to promote neurorepair in an inflammatory CNS demyelination
      model of MS, experimental autoimmune encephalomyelitis (EAE). Combination
      treatment with suboptimal doses of these drugs in an established case of EAE
      (clinical disease score > or = 2.0) significantly attenuated the infiltration of
      inflammatory cells and protected myelin sheath and axonal integrity in the CNS.
      It was accompanied with elevated level of cyclic AMP and activation of its
      associated protein kinase A. Interestingly, combination treatment with these
      drugs impeded neurodegeneration and promoted neurorepair in established EAE
      animals (clinical disease score > or = 3.5) as verified by quantitative real-time
      polymerase chain reaction, immunohistochemistry and electron microscopic
      analyses. These effects of combination therapy were minimal and/or absent with
      either drug alone in these settings. Together, these data suggest that
      combination therapy with LOV and RLP has the potential to provide neuroprotection
      and promote neurorepair in MS, and may have uses in other related CNS
      demyelinating diseases.

PMID- 18720409
TI  - Real-time passive volume responses of astrocytes to acute osmotic and ischemic
      stress in cortical slices and in vivo revealed by two-photon microscopy.
AB  - The brain swells over the several minutes that follow stroke onset or acute hypo
      osmotic stress because cells take up water. Measuring the volume responses of
      single neurons and glia has necessarily been confined to isolated or cultured
      cells. Two-photon laser scanning microscopy enables real-time visualization of
      cells functioning deep within living neocortex in vivo or in brain slices under
      physiologically relevant osmotic and ischemic stress. Astrocytes and their
      processes expressing green fluorescent protein in murine cortical slices swelled
      in response to 20 min of overhydration (-40 mOsm) and shrank during dehydration
      (+40 or +80 mOsm) at 32-34 degrees C. Minute-by-minute monitoring revealed no
      detectable volume regulation during these osmotic challenges, particularly during
      the first 5 min. Astrocytes also rapidly swelled in response to elevated [K+](o)
      for 3 min or oxygen/glucose deprivation (OGD) for 10 min. Post-OGD, astroglial
      volume recovered quickly when slices were re-supplied with oxygen and glucose,
      while neurons remained swollen with beaded dendrites. In vivo, rapid astroglial
      swelling was confirmed within 6 min following intraperitoneal water injection or
      during the 6-12 min following cardiac arrest. While the astrocytic processes were
      clearly swollen, the extent of the astroglial arbor remained unchanged. Thus, in
      contrast to osmo-resistant pyramidal neurons (Andrew et al., 2007) that lack
      known aquaporins, astrocytes passively respond to acute osmotic stress,
      reflecting functional aquaporins in their plasma membrane. Unlike neurons,
      astrocytes better recover from brief ischemic insult in cortical slices, probably
      because their aquaporins facilitate water efflux.

PMID- 18720410
TI  - BMP-2 increases migration of human chondrosarcoma cells via PI3K/Akt pathway.
AB  - Bone morphogenetic protein-2 (BMP-2), a member of transforming growth factor-beta
      superfamily, plays a crucial role in migration and metastasis of human cancer
      cells. Integrins are the major adhesive molecules in mammalian cells. Here we
      found that BMP-2 directed the migration and increased cell surface and mRNA
      expression of beta1 integrin in human chondrosarcoma cancer cells (JJ012).
      Pretreated of JJ012 cells with phosphatidylinositol 3-kinase inhibitor (PI3K;
      Ly294002) or Akt inhibitor inhibited the BMP-2-mediated migration and integrin
      expression. BMP-2 increased the phosphorylation of p85 subunit of PI3K and serine
      473 of Akt. In addition, NF-kappaB inhibitor (PDTC) or IkappaB protease inhibitor
      (TPCK) also inhibited BMP-2-mediated cells migration and integrin upregulation.
      Stimulation of JJ012 cells with BMP-2 induced IkappaB kinase (IKKalpha/beta)
      phosphorylation, IkappaB phosphorylation, p65 Ser(536) phosphorylation, and
      kappaB-luciferase activity. Furthermore, the BMP-2-mediated increasing of
      IKKalpha/beta phosphorylation, IkappaB phosphorylation, and p65 Ser(536)
      phosphorylation were inhibited by Ly294002 and Akt inhibitor. Co-transfection
      with p85 and Akt mutants also reduced the BMP-2-induced kappaB-luciferase
      activity. Taken together, these results suggest that the BMP-2 acts through
      PI3K/Akt, which in turn activates IKKalpha/beta and NF-kappaB, resulting in the
      activations of beta1 integrin and contributing the migration of human
      chondrosarcoma cells.

PMID- 18720411
TI  - Spatiotemporal dynamics of lipid signaling: protein kinase C as a paradigm.
AB  - The lipid second messenger diacylglycerol (DAG) controls the rate, amplitude,
      duration, and location of protein kinase C (PKC) activity in the cell. There are
      three classes of PKC isozymes and, of these, the conventional and novel isozymes
      are acutely controlled by DAG. The kinetics of DAG production at various
      intracellular membranes, the intrinsic affinity of specific isoforms for DAG
      containing membranes, the coordinated use of additional membrane-binding modules,
      the intramolecular regulation of DAG sensitivity, and the competition from other
      DAG-responsive proteins together result in a unique, context-dependent activation
      signature for each isoform. This review focuses on the spatiotemporal dynamics of
      PKC activation and how it is controlled by lipid second messengers.

PMID- 18720412
TI  - A quantitative study of spinothalamic neurons in laminae I, III, and IV in lumbar
      and cervical segments of the rat spinal cord.
AB  - The major ascending outputs from superficial spinal dorsal horn consist of
      projection neurons in lamina I, together with neurons in laminae III-IV that
      express the neurokinin 1 receptor (NK1r) and have dendrites that enter the
      superficial laminae. Some neurons in each of these populations belong to the
      spinothalamic tract, which conveys nociceptive information via the thalamus to
      cortical areas involved in pain. A projection from the cervical superficial
      dorsal horn to the posterior triangular nucleus (PoT) has recently been
      identified. PoT is at the caudal end of the thalamus and was not included in
      injection sites in many previous retrograde tracing studies. We have injected
      various tracers (cholera toxin B subunit, Fluoro-Gold, and fluorescent latex
      microspheres) into the thalamus to estimate the number of spinothalamic neurons
      in each of these two populations, and to investigate their projection targets.
      Most lamina I and lamina III/IV NK1r-immunoreactive spinothalamic neurons in
      cervical and lumbar segments could be labeled from injections centered on PoT.
      Our results suggest that there are 90 lamina I spinothalamic neurons per side in
      C7 and 15 in L4 and that some of those in C7 only project to PoT. We found that
      85% of the lamina III/IV NK1r-immunoreactive neurons in C6 and 17% of those in L5
      belong to the spinothalamic tract, and these apparently project exclusively to
      the caudal thalamus, including PoT. Because PoT projects to second somatosensory
      and insular cortices, our results suggest that these are major targets for
      information conveyed by both these populations of spinothalamic neurons.

PMID- 18720414
TI  - Special issue dedicated to Professor Domenico Misiti.

PMID- 18720413
TI  - Ultrastructural localization of extranuclear progestin receptors in the rat
      hippocampal formation.
AB  - Progesterone's effects on hippocampus-dependent behavior and synaptic
      connectivity maybe mediated through the progestin receptor (PR). Although
      estrogen induces PR mRNA and cytosolic PR in the hippocampus, nuclear PR
      immunoreactivity is undetectable by light microscopy, suggesting that PR is
      present at extranuclear sites. To determine whether this is the case, we used
      immunoelectron microscopy to examine PR distribution in the hippocampal formation
      of proestrus rats. Ultrastructural analysis revealed that PR labeling is present
      in extranuclear profiles throughout the CA1 and CA3 regions and dentate gyrus,
      and, in contrast to light microscopic findings, in nuclei of a few pyramidal and
      subgranular zone cells. Most neuronal PR labeling is extranuclear and is divided
      between pre- and postsynaptic compartments; approximately 30% of labeled profiles
      were axon terminals and 30% were dendrites and dendritic spines. In most laminae,
      except in CA3 stratum lucidum, about 15% of PR-immunoreactive profiles were
      unmyelinated axons. In stratum lucidum, where the mossy fiber axons course, more
      than 50% of PR-labeled profiles were axonal. The remaining 25% of PR-labeled
      profiles were glia, some resembling astrocytes. PR labeling is strongly dependent
      on estrogen priming, insofar as few PR-labeled profiles were detected in
      ovariectomized, oil-replaced females. Synapses formed by PR-labeled terminals
      were predominantly asymmetric, consistent with a role for progesterone in
      directly regulating excitatory transmission. These findings suggest that some of
      progesterone's actions in the hippocampal formation may be mediated by direct and
      rapid actions on extranuclear PRs and that PRs are well positioned to regulate
      progesterone-induced changes at synapses.

PMID- 18720415
TI  - Augmentation of screw fixation with injectable calcium sulfate bone cement in
      ovariectomized rats.
AB  - The objective of this study was to determine the effect of augmenting screw
      fixation with an injectable calcium sulfate cement (CSC) in the osteoporotic bone
      of ovariectomized rats. The influence of the calcium sulfate (CS) on bone
      remodeling and screw anchorage in osteoporotic cancellous bone was systematically
      investigated using histomorphometric and biomechanical analyses. The femoral
      condyles of 55 Sprague-Dawley ovariectomized rats were implanted with screw
      augmented with CS, while the contralateral limb received a nonaugmented screw. At
      time intervals of 2, 4, 8, 12, and 16 weeks, 11 rats were euthanized. Six pair
      matched samples were used for histological analysis, while five pair-matched
      samples were preserved for biomechanical testing. Histomorphometric data showed
      that CS augmented screws activated cancellous bone formation, evidenced by a
      statistically higher (p < 0.05) percentage of osteoid surface at 2, 4, and 8
      weeks and a higher rate of bone mineral apposition at 12 weeks compared with
      nonaugmented screws. The amount of the bone-screw contact at 2, 8, and 12 weeks
      and of bone ingrowth on the threads at 4 and 8 weeks was greater in the CS group
      than in the nonaugmented group (p < 0.05), although these parameters increased
      concomitantly with time for both groups. The CS was resorbed completely at 8
      weeks without stimulating fibrous encapsulation on the screw surface. Also, the
      cement significantly increased the screw pull-out force and the energy to failure
      at 2, 4, 8, and 12 weeks after implantation, when compared with the control group
      (p < 0.05). These results imply that augmentation of screw fixation with CS may
      have the potential to decrease the risk of implant failure in osteoporotic bone.

PMID- 18720416
TI  - One-step preparation of glycopeptide microspheres based on alpha-amino acid-N
      carboxyanhydride polymerization using interfacial protocols.
AB  - A type of polysaccharide-polypeptide hybrid material, chitin derivative with
      polypeptide side chains was prepared by the graft copolymerization of L-leucine N
      carboxyanhydride triggered by water-soluble chitin (WSC). The studies on surface
      tension and aggregation demonstrated surface activity of WSC. Using this
      extraordinary property, the microspheres were synchronously obtained via
      interfacial polymerization. The method employed here to form the microspheres was
      in direct contrast to previous syntheses that used either templating method or
      oil-in-water emulsion. The study provided a facile approach for synthesizing
      microspheres with a variety of distinct polypeptide and regulated graft length,
      which had mimetic structure of glycoconjugation in extracellular matrix.
      Furthermore, the swelling capability of the microsphere in both acidic aqueous
      and organic solvents would give promising application in drug delivery.

PMID- 18720417
TI  - Poly(methyl methacrylate)-grafted chitosan microspheres for controlled release of
      ampicillin.
AB  - Microspheres of 50-500 microm diameter were prepared from a blend of chitosan and
      chitosan-g-PMMA. Environmental scanning electron microscopic and SEM studies
      revealed that the microspheres are porous and the pores extend toward the inner
      core of the microspheres. The microspheres were also found to be hemocompatible
      and cytocompatible. A model drug ampicillin was used to evaluate the drug loading
      capacity and the controlled release properties of the microspheres. The system
      maintained a sustained release of ampicillin for a period of more than 8 days.
      The drug-loaded chitosan/chitosan-g-PMMA microspheres exhibited higher
      antibacterial activity for both the gram positive (ATCC 25923 S. aureus) and gram
      negative (ATCC 25922 E. coli) bacteria than the drug-loaded virgin chitosan
      microspheres. The percentage release and bioactivity of ampicillin was found to
      be higher for the chitosan/chitosan-g-PMMA microspheres than the virgin chitosan
      microspheres. Potential applications such as oral drug delivery, wound dressings,
      tissue engineering, and so forth, are envisaged from these microspheres.

PMID- 18720418
TI  - Erythrocyte programmed cell death.
AB  - Eryptosis, the suicidal death of erythrocytes, is characterised by cell
      shrinkage, membrane blebbing and cell membrane phospholipid scrambling with
      phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing
      erythrocytes are recognised by macrophages, which engulf and degrade the affected
      cells. Reported triggers of eryptosis include osmotic shock, oxidative stress,
      energy depletion, ceramide, prostaglandin E(2), platelet activating factor,
      hemolysin, listeriolysin, paclitaxel, chlorpromazine, cyclosporine,
      methylglyoxal, amyloid peptides, anandamide, Bay-5884, curcumin, valinomycin,
      aluminium, mercury, lead and copper. Diseases associated with accelerated
      eryptosis include sepsis, malaria, sickle-cell anemia, beta-thalassemia, glucose
      6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron
      deficiency, hemolytic uremic syndrome and Wilsons disease. Eryptosis may be
      inhibited by erythropoietin, adenosine, catecholamines, nitric oxide (NO) and
      activation of G-kinase. Most triggers of eryptosis except oxidative stress are
      effective without activation of caspases. Their signalling involves formation of
      prostaglandin E(2) with subsequent activation of cation channels and Ca2+ entry
      and/or release of platelet activating factor (PAF) with subsequent activation of
      sphingomyelinase and formation of ceramide. Ca2+ and ceramide stimulate
      scrambling of the cell membrane. Ca2+ further activates Ca2+-sensitive K+
      channels leading to cellular KCl loss and cell shrinkage and stimulates the
      protease calpain resulting in degradation of the cytoskeleton. Eryptosis allows
      defective erythrocytes to escape hemolysis. On the other hand, excessive
      eryptosis favours the development of anemia. Thus, a delicate balance between
      proeryptotic and antieryptotic mechanisms is required to maintain an adequate
      number of circulating erythrocytes and yet avoid noneryptotic death of injured
      erythrocytes.

PMID- 18720419
TI  - Elevated synaptophysin I in the prefrontal cortex of human chronic alcoholics.
AB  - Convergent lines of evidence suggest potentiation of glutamatergic synapses after
      chronic ethanol exposure, and indicate that the presynaptic effect hereof is on
      modulators of synaptic strength rather than on executors of glutamate release. To
      address this hypothesis in the context of ethanol dependence in humans, we used
      semiquantitative immunoblotting to compare the immunoreactivities of
      synaptophysin I, syntaxin 1A, synaptosome-associated protein 25, and vesicle
      associated membrane protein in the prefrontal and motor cortices between chronic
      alcoholics and control subjects. We found a region-specific elevation in
      synaptophysin I immunoreactivity in the prefrontal cortex of alcoholics, but
      detected no significant differences between the groups in the immunoreactivities
      of the other three proteins. Our findings are consistent with an effect of
      repeated ethanol exposure on modulators of synaptic strength but not on executors
      of glutamate release, and suggest a role for synaptophysin I in the enduring
      neuroplasticity in the prefrontal cortical glutamate circuitry that is associated
      with ethanol dependence.

PMID- 18720420
TI  - Extracellular dopamine induces the oxidative toxicity of SH-SY5Y cells.
AB  - Dopamine-induced neuronal cytotoxicity has been proposed as a leading
      pathological mechanism underlying many neuronal degenerative disorders including
      Parkinson disease. Various hypotheses have been proposed including oxidative
      stress and dopamine (DA)-induced intracellular signal disorder via DA D1 and D2
      receptors. The exact mechanism involved in this process is far from clear. In
      this study, employing a neuronal blastoma cell line, SH-SY5Y, we tried to
      elucidate the roles of these different suggested mechanisms in this pathological
      process. The results showed that DA induced cell toxicity in a dose- and time
      dependent way. Selective D1 and D2 DA receptor antagonist could not block the
      cytotoxic effects, whereas reductive reagent ascorbic acid but not GSH could
      effectively rescue the cell death, suggesting that DA-induced cell toxicity was
      caused by an extracellular oxidative stress. This was further supported by the
      enhancing effects of DA transporter blocker, GBR, which could increase the cell
      death when pretreated. Finally, ascorbic acid could also protect SY5Y cells from
      DA-induced cellular apoptotic signal changes including PARP and P53. Our studies
      suggested that DA exerted its cytotoxic effects via an extracellular metabolism,
      whereas intracellular transportation could reduce its oxidative stress.
      Cytotoxicity effects induced by extracellular DA could be protected by reductive
      agents as ascorbic acid. These results help to broaden our understanding of the
      mechanisms of DA-induced cell death and may provide potentially therapeutical
      alternative for the neurodegenerative disorders.

PMID- 18720421
TI  - Aripiprazole and its human metabolite OPC14857 reduce, through a presynaptic
      mechanism, glutamate release in rat prefrontal cortex: possible relevance to
      neuroprotective interventions in schizophrenia.
AB  - Aripiprazole is a novel atypical antipsychotic drug with neuroprotective
      properties. As excessive glutamate release is now considered to be part of the
      pathophysiology of schizophrenia, the objective of this study was to use an in
      vitro assay system to investigate the effect of aripiprazole and its human
      metabolite OPC14857 on the release of endogenous glutamate from isolated nerve
      terminals (synaptosomes), freshly prepared from rat prefrontal cortex. Both
      aripiprazole and OPC13857 potently inhibited 4-aminopyridine (4-AP)-evoked
      glutamate release in a concentration-dependent manner. Inhibition of glutamate
      release by aripiprazole and OPC13857 was associated with a reduction of 4AP
      evoked Na+ influx and depolarization, as well as downstream elevation of
      cytoplasmic free calcium concentration mediated via N- and P/Q-type voltage
      dependent Ca2+ channels (VDCCs). Release induced by direct Ca2+ entry with Ca2+
      ionophore (ionomycin) was unaffected by aripiprazole or OPC13857, indicating that
      the inhibitory effect of aripiprazole or OPC13857 is not due to directly
      interfering with the release process at some point subsequent to Ca2+ influx. In
      addition, the dopamine D2 receptor antagonist haloperidol and the 5-HT 1A
      receptor antagonist WAY100635 all effectively blocked the aripiprazole or
      OPC13857-mediated inhibition of 4-AP-evoked glutamate release. Moreover,
      aripiprazole or OPC13857 modulation of 4-AP-evoked glutamate release appears to
      involve a protein kinase A (PKA) signaling cascade, insofar as pretreatment of
      synaptosomes with the PKA inhibitor H89 suppressed the inhibitory effect of
      aripiprazole or OPC13857. Together, these results suggest that aripiprazole and
      its human metabolite OPC14857 inhibit glutamate release from rat
      prefrontocortical nerve terminals, likely by the activation of dopamine D2 and 5
      HT 1A receptors, which subsequently results in the reduction of nerve terminal
      excitability and downstream VDCC activation through a signaling cascade involving
      PKA. These actions of aripiprazole may contribute to its neuroprotective effect
      in excitotoxic injury.

PMID- 18720422
TI  - Phencyclidine and glutamate agonist LY379268 stimulate dopamine D2High receptors:
      D2 basis for schizophrenia.
AB  - It has previously been reported that the glutamate ionotropic antagonist
      phencyclidine directly inhibits the release of prolactin in anterior pituitary
      cells in culture, suggesting that phencyclidine has a dopamine (DA)-like action
      on prolactin-releasing cells. It has also been reported that the glutamate
      metabotropic agonist LY379268 can stimulate the incorporation of [35S]GTP-gamma-S
      into DA D2Long receptors. The present study was done to examine whether such
      glutamatergic drugs had similar actions on the DA D2Short receptor. The present
      results show that phencyclidine, ketamine, and LY379268 also stimulated the
      incorporation of [35S]GTP-gamma-S into D2Short receptors. The proportion of
      D2Long and D2Short receptors existing in the high-affinity state were both
      markedly reduced by NaCl. While phencyclidine and LY379268 each stimulated the
      incorporation of GTP-gamma-S into D2Long and D2Short receptors, this stimulation
      was reduced by NaCl, with D2Short being much more sensitive than D2Long to the
      inhibition by NaCl. The binding of phencyclidine and LY379268 to D2High receptors
      in vivo was directly confirmed by the i.v. injection of phencyclidine and
      LY379268 in which 50% inhibited the binding of [3H]PHNO to the striatum ex vivo
      at 0.25 and 1.5 mg/kg, respectively. The results confirm that glutamate agonists
      and antagonists have a significant affinity for DA D2High receptors. The
      psychotogenic action of phencyclidine may stem from a combination or synergistic
      action of glutamate receptor antagonism and DA D2 agonism. In addition, the
      antipsychotic clinical action of LY379268 congeners such as LY404039 may be
      related to a combined or synergistic action of glutamate receptor stimulation
      together with a partial DA agonist action that reduces endogenous DA
      neurotransmission.

PMID- 18720423
TI  - In vitro sodium nitroprusside-mediated toxicity towards Leishmania amazonensis
      promastigotes and axenic amastigotes.
AB  - Leishmania parasites survive despite exposure to the toxic nitrosative oxidants
      during phagocytosis by the host cell. In this work, the authors investigated
      comparatively the resistance of Leishmania amazonensis promastigotes and axenic
      amastigotes to a relatively strong nitrosating agent that acts as a nitric oxide
      (NO) donor, sodium nitroprusside (SNP). Results demonstrate that SNP is able to
      decrease, in vitro, the number of L. amazonensis promastigotes and axenic
      amastigotes in a dose-dependent maner. Promastigotes, cultured in the presence of
      0.25, 0.5, and 1 mmol L(-1) SNP for 24 h showed about 75% growth inhibition, and
      97-100% when the cultures were treated with >2 mmol L(-1) SNP. In contrast, when
      axenic amastigotes were growing in the presence of 0.25-8 mM SNP added to the
      culture medium, 50% was the maximum of growth inhibition observed. Treated
      promastigotes presented reduced motility and became round in shape further
      confirming the leishmanicidal activity of SNP. On the other hand, axenic
      amastigotes, besides being much more resistant to SNP-mediated cytotoxicity, did
      not show marked morphological alteration when incubated for 24 h, until 8 mM
      concentrations of this nitrosating agent were used. The cytotoxicity toward L.
      amazonensis was attenuated by reduced glutathione (GSH), supporting the view that
      SNP-mediated toxicity triggered multiple oxidative mechanisms, including
      oxidation of thiols groups and metal-independent oxidation of biomolecules to
      free radical intermediates.

PMID- 18720426
TI  - Understanding and analysis of CAOS development in context: the case of China.
AB  - BACKGROUND: Computer-assisted orthopaedic surgery (CAOS) has great advantages in
      precise determination of focus, planning an optimal surgical project and assuring
      the success of operation. In adopting CAOS, China is facing many problems,
      gaining experience and learning lessons. METHODS: A literature review of the
      current development of CAOS in China and case studies, including adopted CAOS
      systems, CAOS clinical applications in the orthopaedic field and emerging CAOS
      research in China was carried out. Experience and lessons gained through adopting
      CAOS in China are also illustrated and analysed. RESULTS AND DISCUSSION: In the
      course of investigating the current development of CAOS in China, existing
      problems were analysed, experience gained and lessons illustrated. CONCLUSIONS:
      By summarizing the Chinese experience and lessons of adopting CAOS, we not only
      deliver an in-depth understanding of present CAOS development and give advice for
      future CAOS development in China; this also has implications for other developing
      countries where CAOS development is burgeoning.

PMID- 18720425
TI  - Re: Jin E and Santo M "Neurite outgrowth of NG08-15 cells induced by heat shock
      protein 90 inhibitors".

PMID- 18720427
TI  - Species identification of Oetzi's clothing with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry based on peptide pattern
      similarities of hair digests.
AB  - Identification of ancient biological samples from the 1991-discovered and more
      than 5300-year-old Tyrolean mummy, also called iceman or Oetzi, is very
      difficult. The species of origins of four animal-hair-bearing samples of the
      accoutrement of the mummy not yet diagnosed were identified by a special
      proteomics method. Ha 43/91/130 and Ha 6/91, two samples from his coat, and Ha
      5/91, a sample from his leggings, were assigned to sheep. The upper leather of
      his moccasins, Ha 2/91, was made from cattle. Despite the enormous age of these
      samples with partial (bio)chemical alterations, reliable identification was
      possible using a recently developed matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometric ((MALDI-TOF MS)-based analytical method. The
      method is exclusively based on the analysis of proteins and uses minute amounts
      of peptides directly derived from tryptic hair digests without any separation or
      enrichment steps. Unknown species are identified by comparison of their peptide
      ion patterns with known spectra stored in existing databases. Hereby, the
      correlation distance, a form of Euclidean distance, and deduced parameters are
      used to measure similarities. If more than one potential hit remains, specific
      diagnostic peptide ions are used to stepwise exclude incorrect matches. These
      ions are specific for orders, families, subfamilies/genera and/or even species.
      Peptide mass fingerprinting data combined with those from collision-induced
      dissociation spectra (combined MS & MS/MS) were used for interpretation with the
      MASCOT search engine and the NCBI database to find the potential parentage of
      hair proteins. For this technique, selected precursor ions were identified as
      specific diagnostic peptide ions.

PMID- 18720428
TI  - Education and drug use in Sweden--a nationwide register-based study.
AB  - PURPOSE: To analyse educational variations in prescriptions dispensed in Sweden.
      A better knowledge of the use of drugs in the population, including socioeconomic
      distribution, is a prerequisite in efforts to estimate whether drugs are being
      prescribed and used according to need. This knowledge may also facilitate the
      identification of selection or confounding factors when analysing outcome or
      adverse side effects of drug treatment. METHODS: All prescriptions dispensed
      during 2006 for 22 different categories of drugs were analysed in the Swedish
      Prescribed Drug Register. Each prescription was linked by a unique personal
      identification number (PIN) to the National Education Register. In total,
      analyses covered 1,557,740 men and 1,568,175 women aged 45-74. RESULTS: Those
      with low education were generally at higher risk of having drugs, odds ratios
      (ORs) varying from 1.2 to 2. Most differences appeared to be of the same
      magnitude as those found in studies of the relation between education and disease
      incidence and prevalence, that is drugs may be prescribed and dispensed according
      to need. However, there are some drugs, such as antibiotics, sildenafil, hormone
      replacement drugs, anti-migraine drugs and angiotensin receptor blockers (ARB),
      where people with higher education have higher consumption than is expected from
      incidence and prevalence data. CONCLUSIONS: There are rather large differences in
      drug utilization between groups of different educational levels. Mostly these
      disparities seem to reflect differences in need, but there are examples of
      inequalities in drug use.

PMID- 18720430
TI  - Lethality in an anti-angiogenic tumor gene therapy model upon constitutive but
      not inducible expression of the soluble vascular endothelial growth factor
      receptor 1.
AB  - BACKGROUND: Neoangiogenesis is essential for tumor growth. The present study
      aimed to test the hypothesis that vector-mediated expression of sflt1 at high
      levels would result in the blockade of vascular endothelial growth factor (VEGF)
      function and therefore the inhibition of tumor growth. METHODS: To sequester
      VEGF, we tested, in a subcutaneous LLC tumor model, 'gutless' high-capacity
      adenovirus vectors expressing the soluble VEGF receptor 1 (sflt1) in a liver
      specific manner, either in a constitutive or in a RU486 induced manner. RESULTS:
      High serum levels of sflt1 were observed upon in vivo injection of both vectors.
      Despite the differences in expression kinetics, both modes of sflt1 expression
      resulted in significant though transient suppression of tumor growth.
      Unexpectedly, constitutive but not intermittent sflt1 expression resulted in
      ascites and death of all animals. Morphological analyses by light and electron
      microscopy indicated that the animals had died from a nephropathy, which
      apparently was due to the blockade of VEGF function. CONCLUSIONS: Although
      confirming earlier results of toxic effects of prolonged VEGF sequestration, the
      present study suggests that therapeutic anti-tumor effects can be achieved
      without side-effects with intermittent VEGF blockade or the use of drugs with
      short half-lives, as shown by the use of an inducible gene expression system.

PMID- 18720429
TI  - Recombinant adeno-associated virus-mediated gene delivery of long chain acyl
      coenzyme A dehydrogenase (LCAD) into LCAD-deficient mice.
AB  - BACKGROUND: Very long chain acyl coenzyme A (CoA) dehydrogenase (VLCAD)
      deficiency is a relatively common mitochondrial beta-oxidation disorder. The most
      severe form of VLCAD deficiency presents with neonatal cardiomyopathy and hepatic
      failure and is generally fatal within the first year of life. Mice deficient for
      long chain acyl CoA dehydrogenase (LCAD) closely resemble the clinical syndrome
      observed in VLCAD-deficient humans. Recombinant adeno-associated viral (rAAV)
      vectors with pseudotype capsids were investigated for their potential towards
      correcting the phenotype observed in mice heterozygous (+/-) for LCAD (i.e. liver
      and muscle steatosis). METHODS: rAAV containing the mouse LCAD cDNA (mLCAD) under
      the transcriptional control of the CMV/chicken beta-actin hybrid promoter were
      injected intramuscularly into the tibialis anterior (TA) muscle of LCAD(+/-) mice
      or injected into the portal vein to transduce hepatocytes. RESULTS: Ten weeks
      post-injection of rAAV1-mLCAD into the TA muscle, significantly increased levels
      of mLCAD within mitochondria were demonstrated by immunostaining of TA sections,
      immunoblotting of mitochondrial isolates and by the electron transfer
      flavoprotein (ETF) fluorescence reduction enzyme activity assay. Magnetic
      resonance spectroscopy of vector-injected TA muscle demonstrated a reduction in
      the lipid content compared to phosphate-buffered saline-injected mice, whereas a
      systemic effect was observed as a reduction in liver macrosteatosis. Eight weeks
      after portal vein injection of rAAV8-mLCAD into LCAD(+/-) mice, increased levels
      of mLCAD within hepatocyte mitochondria were demonstrated by immunostaining and
      also by the ETF assay. Scoring of the hepatosteatosis observed in partially
      deficient LCAD mice indicated a reduction in the lipid content within livers of
      vector-treated mice. CONCLUSIONS: These studies show that rAAV-mediated delivery
      of mLCAD was efficient and led to an amelioration of local and systemic
      pathologies observed in partially deficient LCAD mice.

PMID- 18720432
TI  - Molecules with new topologies derived from hydrogen-bonded dimers of tetraurea
      calix[4]arenes.
AB  - Tetraurea calix[4]arenes 2 have been synthesized in which two adjacent aryl urea
      residues are connected to a loop by an aliphatic chain -O-(CH(2))(n)-O-. The
      remaining urea residues have a bulky 3,5-di-tert-butylphenyl residue and an omega
      alkenyloxyphenyl residue. Since this bulky residue cannot pass through the loop,
      only one homodimer (22) is formed in apolar solvents, for steric reasons, in
      which the two alkenyl residues penetrate the two macrocyclic loops. Covalent
      connection of these alkenyl groups by olefin metathesis followed by hydrogenation
      creates compounds 3, which consist of molecules with hitherto unknown topology.
      Their molecular structure was confirmed by (1)H NMR spectroscopy and ESIMS, and
      for one example by single-crystal X-ray analysis.

PMID- 18720431
TI  - Comparison of elderly suicide rates among migrants in England and Wales with
      their country of origin.
AB  - BACKGROUND: The black and minority ethnic (BME) elderly population size in
      England and Wales has progressively increased over the last three decades. Only
      two studies, both well over a decade old, have compared suicide rates in BME
      groups in England and Wales with those in their country of origin. METHODS: A
      study comparing suicide rates among elderly migrants in England and Wales and in
      their country of origin using the latest available mortality data from the Office
      of National Statistics and the World Health Organization was conducted. RESULTS:
      There were wide variations in standardised mortality ratios for elderly suicides
      among migrants from different countries compared with those born in England and
      Wales and in their country of origin. There was convergence towards elderly
      suicide rates for England and Wales in some migrant groups in males in the age
      bands 65-74 years and 75 + years, and in females in the age-band 75 + years.
      However, males aged 75 + years from most migrant groups had higher rates than
      those born in England and Wales. CONCLUSION: A more detailed analysis of suicide
      of older people from migrant groups is required to determine vulnerability and
      protective influences.

PMID- 18720433
TI  - Complexity emerges from lattice overlapping: implications for nanopatterning.

PMID- 18720434
TI  - Microtubule alignment and manipulation using AC electrokinetics.
AB  - The kinesin-microtubule system plays an important role in intracellular transport
      and is a model system for integrating biomotor-driven transport into
      microengineered devices. AC electrokinetics provides a novel tool for
      manipulating and organizing microtubules in solution, enabling new experimental
      geometries for investigating and controlling the interactions of microtubules and
      microtubule motors in vitro. By fabricating microelectrodes on glass substrates
      and generating AC electric fields across solutions of microtubules in low-ionic
      strength buffers, bundles of microtubules are collected and aligned and the
      electrical properties of microtubules in solution are measured. The AC electric
      fields result in electro-osmotic flow, electrothermal flow, and dielectrophoresis
      of microtubules, which can be controlled by varying the solution conductivity, AC
      frequency, and electrode geometry. By mapping the solution conductivity and AC
      frequency over which positive dielectrophoresis occurs, the apparent conductivity
      of taxol-stabilized bovine-brain microtubules in PIPES buffer is measured to be
      250 mS m(-1). By maximizing dielectrophoretic forces and minimizing electro
      osmotic and electrothermal flow, microtubules are assembled into opposed asters.
      These experiments demonstrate that AC electrokinetics provides a powerful new
      tool for kinesin-driven transport applications and for investigating the role of
      microtubule motors in development and maintenance of the mitotic spindle.

PMID- 18720435
TI  - Photostable second-harmonic generation from a single KTiOPO4 nanocrystal for
      nonlinear microscopy.

PMID- 18720436
TI  - Understanding the kinetics and nanoscale morphology of electron-beam-induced
      deposition via a three-dimensional Monte Carlo simulation: the effects of the
      precursor molecule and the deposited material.
AB  - The electron-beam-induced deposition of silicon oxide from tetraethyorthosilicate
      and tungsten from tungsten hexafluoride is simulated via a Monte Carlo
      simulation. Pseudo one-dimensional nanopillars are grown using comparable
      electron-beam parameters and a comparison of the vertical and lateral growth rate
      and the pillar morphology is correlated to the precursor and deposited material
      parameters. The primary and secondary electrons (type I) are found to dominate
      the vertical growth rate and the lateral growth rate is dominated by forward and
      secondary electrons (type II). The resolution and morphology of the nanopillars
      are affected by the effective electron interaction volume and the resultant
      surface coverage of the precursor species in the effective electron interaction
      region. Finally, the simulated results are compared to previously reported
      experimental results.

PMID- 18720437
TI  - Individual nanometer hole-particle pairs for surface-enhanced Raman scattering.

PMID- 18720438
TI  - Synthesis of polyhedral ZnSnO3 microcrystals with controlled exposed facets and
      their selective gas-sensing properties.

PMID- 18720439
TI  - Chiral recognition of amino acids based on cyclodextrin-capped quantum dots.

PMID- 18720440
TI  - Carbon nanotubes conjugated to tumor lysate protein enhance the efficacy of an
      antitumor immunotherapy.
AB  - The biomedical applications of carbon nanotubes (CNTs) have attracted deep
      interest in recent years. Antitumor immunotherapy has the potential to improve
      the prognosis of cancer treatment but the efficacy of current immunotherapy
      generally needs further improvement. Multi-walled CNTs conjugated to tumor lysate
      protein are investigated as to whether they would enhance the efficacy of an
      immunotherapy employing a tumor-cell vaccine in a mouse model bearing the H22
      liver cancer. The tumor cure rate is found to be markedly improved by CNTs
      conjugated to tumor lysate protein. The cellular antitumor immune reaction is
      also enhanced. Moreover, the observed antitumor immune response is relatively
      specific against the tumor intended for treatment. These findings suggest that
      CNTs may have a prospective role in the development of new antitumor
      immunotherapies.

PMID- 18720441
TI  - High-fidelity formation of a molecular-junction device using a thickness
      controlled bilayer architecture.
AB  - The device yield of molecular junctions has become a major issue for the
      practical application of molecular electronics based on a crossbar system of a
      metal-molecule-metal (MMM) junction. As the thickness of self-assembled
      monolayers (SAMs) is typically 1-2 nm, it is difficult to avoid electrical shorts
      due to the penetration of top metal particles into the SAMs. A simple and
      effective strategy for the creation of a reliable molecular junction using a
      thickness-controlled bilayer with a bifunctional heterostructure is presented. In
      the MMM device, the Au adlayer on the molecular layer is spontaneously formed
      with deposition of the top Au metals and the sandwiched molecular layer maintains
      the quality of the SAMs. This method greatly reduces electrical shorts by
      preventing the diffusion of the top metal electrode and offsetting the surface
      roughness of the bottom metal electrode, resulting in a device yield of more than
      90%.

PMID- 18720442
TI  - Electrostatic self-assembly of charged colloids and macromolecules in a fluidic
      nanoslit.

PMID- 18720443
TI  - Targeted delivery of nanoparticles bearing fibroblast growth factor-2 by
      ultrasonic microbubble destruction for therapeutic arteriogenesis.
AB  - Therapeutic strategies in which recombinant growth factors are injected to
      stimulate arteriogenesis in patients suffering from occlusive vascular disease
      stand to benefit from improved targeting, less invasiveness, better growth-factor
      stability, and more sustained growth-factor release. A microbubble contrast-agent
      based system facilitates nanoparticle deposition in tissues that are targeted by
      1-MHz ultrasound. This system can then be used to deliver poly(D,L-lactic-co
      glycolic acid) nanoparticles containing fibroblast growth factor-2 to mouse
      adductor muscles in a model of hind-limb arterial insufficiency. Two weeks after
      treatment, significant increases in both the caliber and total number of
      collateral arterioles are observed, indicating that the delivery of nanoparticles
      bearing fibroblast growth factor-2 by ultrasonic microbubble destruction may
      represent an effective and minimally invasive strategy for the targeted
      stimulation of therapeutic arteriogenesis.

PMID- 18720444
TI  - Effect of holding time, temperature and different parenteral solutions on
      viability and functionality of adult bone marrow-derived mesenchymal stem cells
      before transplantation.
AB  - Mesenchymal stem cells (MSCs) have the ability to proliferate and differentiate
      into various lineages, given the appropriate microenvironment, thus making MSCs
      promising candidates for cell transplantation. For clinical applications, MSCs
      need to be stored in optimal conditions so that they may be transported and made
      available as an off-the-shelf product for companies to market. Freshly harvested
      and cultured or frozen-thawed bone marrow-derived MSCs were prepared for cell
      transplantation. Both freshly cultured or frozen-thawed MSCs were washed and
      resuspended in parenteral solutions, either 0.9% saline, Dulbecco's phosphate
      buffered saline (DPBS), plasmalyte A or 5%dextrose and held for 2, 4, 6 and 8 h
      at 4 degrees C, 37 degrees C and RT (22 degrees C). The viability of the cells,
      differentiation capability and expression of cell surface markers were analysed.
      MSCs harvested from fresh cultures, resuspended in the parenteral solutions and
      maintained at 4 degrees C for 6 h showed more than 90% viability, and the
      viability was appreciably better when suspended in 5% dextrose at 4 degrees C for
      8 h. In contrast, frozen-thawed cells can be held for a maximum of 2 h after
      thawing before losing their viability significantly below permissible limits for
      transplantation. We are reporting for the first time the effect of various
      parenteral solutions, holding times and temperatures on the viability and
      functionality of bone marrow-derived freshly cultured or frozen-thawed MSCs for
      transplantation. Our results suggested that freshly harvested MSCs can be held
      for 8 h at 4 degrees C in 5% dextrose or for up to 6 h at 4 degrees C in saline,
      DPBS or plasmalyte A. Freeze-thawed MSCs can be held for a maximum of 2 h in
      plasmalyte A before transplantation without affecting their viability and ability
      to differentiate.

PMID- 18720445
TI  - Synergy between myogenic and non-myogenic cells in a 3D tissue-engineered
      craniofacial skeletal muscle construct.
AB  - In vitro skeletal muscle engineering involves the culture of isolated primary
      myogenic cells in an environment conducive to the formation of a three
      dimensional (3D) tissue construct capable of generating force. Isolated human
      myogenic cells have been used to study cell-cell interactions, permitting
      identification of functions intrinsic to skeletal muscle in two dimensions (2D).
      However, the independent contribution of human myogenic and non-myogenic cell
      types that comprise skeletal muscle to myogenic cell differentiation, force
      generation and matrix remodelling has yet to be established in 3D. The objective
      of this study was to use isolated human myogenic and non-myogenic muscle-derived
      cells (MDC) seeded in 3D collagen constructs to engineer a biomimetic
      craniofacial skeletal construct. The aim was to purify the two subpopulations of
      myogenic and non-myogenic cells from human masseter muscle and quantitate
      myogenic cell differentiation, force generation and matrix remodelling of the 3D
      collagen construct. The results showed that both the heterogeneous mixture of
      cells and the purified myogenic cell population expressed myogenin, indicative of
      myogenic cell differentiation. Further, there was a synergistic effect as the
      heterogeneous co-culture of myogenic and non-myogenic cells generated the highest
      peak force and expressed the most MMP-2 mRNA compared to isolated individual cell
      populations.

PMID- 18720446
TI  - Allergenic compounds on the inner and outer surfaces of natural latex gloves:
      MALDI mass spectrometry and imaging of proteinous allergens.
AB  - Natural latex gloves are the cause of a severe health problem to an increasing
      number of healthcare workers or patients due to the presence of protein allergens
      as Hevein or Rubber Elongation Factor (REF). One of the most challenging problems
      is the in situ localization of theses allergens in, e.g. gloves, to estimate the
      allergenic potential of the latex material. A sample preparation protocol
      applying a binary matrix-assisted laser desorption/ionization(MALDI) matrix
      containing alpha-cyano-4-hydroxy cinnamic acid (CHCA) and 2,5-dihydroxy benzoic
      acid (DHB) on trifluoro acetic acid (TFA) etched latex glove surfaces allowed the
      direct determination (exact molecular weight) of Hevein, REF and a truncated form
      of REF (tREF) within nine different brands of natural latex gloves by means of
      MALDI-TOF-MS in the linear mode. MALDI mass spectrometry demonstrated that
      Hevein, tREF and REF were present on the inner surfaces (in direct contact with
      the skin) of many, but not all, investigated gloves without any prior extraction
      procedure. Additionally, different isoforms of the allergen Hevein were detected
      (exhibiting ragged C-termini). tREF and REF could always be detected beside each
      other, but were not observed on every latex glove sample, which contained Hevein.
      It was also demonstrated that there is a significant difference in terms of
      proteins and polymers between inner and outer surfaces of gloves, which helps to
      explain the different allergenic potential of these.MALDI imaging allowed for the
      first time the unambiguous localization of all three allergens in parallel and
      showed that Hevein was present on 36% of the investigated area of a latex glove
      with a certain localization, whereupon, tREF and REF were only found on 25% of
      the investigated material.

PMID- 18720447
TI  - DFT/NMR integrated approach: a valid support to the total synthesis of chiral
      molecules.
AB  - The analysis of the configuration of kedarcidin chromophore and palau'amine
      through quantum chemical calculation of Js and chemical shifts suggests a fast
      and convenient quantum chemical approach that can be applied prior to proceeding
      to the total synthesis of complex natural compounds in order to avoid loss of
      time and resources employed in the total synthesis of wrong diastereoisomers.

PMID- 18720448
TI  - Structure elucidation and NMR spectral assignments of four neolignan glycosides
      with enantiometric aglycones from Osmanthus ilicifolius.
AB  - Four new 8-O-4' type neolignan glycosides with enantiometric aglycones, (7S,8R)
      erythro-guaiacylglycerol-beta-O-4'-sinapyl ether 9-O-beta-D-glucopyranoside (1),
      (7R,8S)-erythro-guaiacylglycerol-beta-O-4'-sinapyl ether 9-O-beta-D
      glucopyranoside (2), (7S,8R)-erythro- syringylglycerol-beta-O-4'-sinapyl ether 9
      O-beta-D-glucopyranoside (3) and (7R,8S)-erythro- syringylglycerol-beta-O-4'
      sinapyl ether 9-O-beta-D-glucopyranoside (4), were isolated from the leaves of
      Osmanthus ilicifolius. Their structures were established on the basis of NMR,
      circular dichroism (CD), MS and chemical data. The NMR assignments for the
      compounds were carried out using (1)H, (13)C, COSY, HMQC, HMBC and NOESY NMR
      experiments.

PMID- 18720449
TI  - Solution structure determination of oligoureas using methylene spin state
      selective NMR at 13C natural abundance.
AB  - Ability of N,N'-linked oligoureas containing proteinogenic side chains to adopt a
      stable helix conformation in solution has been described recently. NMR as well as
      circular dichroism (CD) spectroscopies were employed to gain insight into their
      specific fold. It is herein proposed to extend the structural information
      available on these peptidomimetics by an advantageous use of a methylene spin
      state selective NMR experiment. Homodecoupling provided by the pulse scheme made
      it possible to readily measure conformation-dependent (3)J(HH) constants that are
      difficult if not impossible to obtain with standard NMR experiments. Adding those
      couplings to the NMR restraints improved the quality of the structure
      calculations significantly, as judged by a ca 30% decrease of the root mean
      square deviation (RMSD) obtained over an ensemble of 20 structures. Moreover,
      accurate determination of individual (1)J(CH) couplings within each methylene
      group revealed uniform values throughout the oligourea sequence, with (1)J(CH)
      systematically slightly larger for the pro-S hydrogen than for the pro-R. As
      shown in this study, the methylene spin state selective NMR experiment displays a
      good intrinsic sensitivity and could therefore provide valuable structural
      information at (13)C natural abundance for peptidomimetic molecules and foldamers
      bearing diastereotopic methylene protons.

PMID- 18720450
TI  - Effect of phosphate electrolyte buffer on the dynamics of water in tendon and
      cartilage.
AB  - A number of NMR spectroscopic and microscopic MRI (microMRI) techniques were used
      to study proton dynamics in canine tendon and articular cartilage immersed in
      normal saline solution (NaCl solution) and high-concentration phosphate-buffered
      saline (PBS) solution. In a proton CPMG experiment on tendons, the T(2)
      relaxation of the tissue was found to be anisotropic and had two populations.
      When immersed in saline, the T(2) values were short and their relative
      populations were anisotropic. When immersed in PBS, the T(2) values increased and
      their relative populations became isotropic. These phenomena, also verified by
      proton double-quantum-filtered (DQF) NMR spectroscopy, were interpreted as the
      catalyzing effect of phosphate ions on proton exchange between water molecules.
      In the experiment on articular cartilage, the immersion of cartilage-bone blocks
      in PBS resulted in a significant reduction in the laminar appearance of cartilage
      on MRI (the magic angle effect). The quantitative T(2) anisotropy by microMRI at
      13 microm pixel resolution and DQF NMR spectroscopy confirmed the substantial
      effect of PBS on the water dynamics in cartilage tissue blocks. This preliminary
      study has two important implications. For in vitro cartilage research, this work
      confirms the importance of the salt solution in which the specimen is stored -
      not all salts have the same effect on the measurable quantities in NMR and MRI.
      For in vivo cartilage diagnosis, especially using whole-body MRI scanners, this
      work suggests the possibility of using a suitable electrolyte as a novel contrast
      agent to assess the ultrastructural changes in cartilage due to tissue
      degradation.

PMID- 18720451
TI  - Heteronuclear dipolar decoupling effects on multiple-quantum and satellite
      transition magic-angle spinning NMR spectra.
AB  - We here report on the influence of heteronuclear dipolar decoupling on the (27)Al
      3QMAS, 5QMAS, and the double-quantum filter-satellite-transition magic-angle
      spinning (DQF-STMAS) spectra of a strongly dipolar-coupled system, gibbsite. The
      requirements for heteronuclear dipolar decoupling increase with the order of
      coherence evolving in the indirect dimension of a two-dimensional (2D)
      experiment. The isotropic line width of the high-resolution 2D spectra, in
      samples like gibbsite, is composed of four parts: the distribution of isotropic
      shifts (delta(ISO), delta(QIS)), the homogeneous broadening related to the proton
      proton flip-flop terms, the (27)Al-(27)Al homonulcear dipolar couplings, and the
      (1)H-(27)Al heteronuclear dipolar couplings. It is shown that, even in the case
      of gibbsite, where a strong proton-proton bath exists, the main resolution
      limiting factor in these experiments resides in the (1)H-(27)Al dipolar
      interaction.

PMID- 18720452
TI  - Professional development of statisticians in the pharmaceutical sector: evolution
      over the past decade and into the future.
AB  - The adoption of The International Conference on Harmonization Tripartite
      Guideline: Statistical Principles for Clinical Trials (ICH-E9) has provided a
      foundation for the application of statistical principles in clinical research and
      raised awareness of the value of a statistical contribution to the wider
      pharmaceutical R&D process. In addition, over the past decade globalization of
      the pharmaceutical R&D process and the measures taken to address reduced
      productivity and spiralling costs have impacted on the roles and career
      opportunities for statisticians working in the pharmaceutical sector. This has
      enhanced the need for continuing professional development to equip statisticians
      with the skills to fully contribute to creating innovative solutions. In the
      future, key areas of focus are the establishment of professional standards for
      statistical work and increasing the collaboration between statisticians working
      in industry, regulatory agencies and academia. In addition, the diversity of
      roles and potential career paths for statisticians embarking on a career in the
      pharmaceutical sector emphasizes the importance of mentoring and coaching. For
      the more experienced statisticians, there are unprecedented opportunities to lead
      and innovate.

PMID- 18720453
TI  - Lack of standardization in determining gestational age for prenatal screening.
AB  - OBJECTIVES: To determine whether estimation of gestational age (GA) in the
      context of first-trimester Down syndrome screening is standardized in the
      Netherlands. METHODS: This was a retrospective study, carried out between January
      2005 and December 2006, of women who underwent first-trimester Down syndrome
      screening (n = 40,730) based on GA, maternal serum analysis and nuchal
      translucency (NT) measurement. Date of the last menstrual period (LMP), dating
      scan information including measurement of crown-rump length (CRL), NT thickness
      and name of the sonographer were recorded for all pregnancies. The accuracy of
      estimation of GA was evaluated by comparing the GA based on the LMP with that
      estimated from the CRL, using relevant subsets of the database. A survey of 104
      sonographers was performed to further investigate the findings of the preceding
      analysis. RESULTS: In 44% of all first-trimester combined tests the estimation of
      GA was based on the dating scan; the method of determination of GA was unknown in
      23%. In 15% of all cases a dating scan was recorded but was not used to provide
      the estimation of GA at blood sampling. Detailed analysis showed that a
      consistent methodology for the estimation of GA from CRL was not maintained
      within hospitals and obstetric practices. For a single CRL, the reported GA
      differed by up to 10 days. Finally, it was demonstrated that individual
      sonographers reported different GAs for a given CRL. CONCLUSIONS: Currently,
      estimation of GA in the first trimester in the Netherlands is not standardized.
      To improve the performance of prenatal screening for Down syndrome, estimation of
      GA should be based on ultrasound examination, with one nationally accepted CRL
      curve.

PMID- 18720454
TI  - Prospective study of colonic irrigation for the treatment of defaecation
      disorders.
AB  - BACKGROUND: Retrograde colonic irrigation is a possible treatment for defaecation
      disorders when conservative treatment or surgery has failed. The aim of this
      prospective study was to investigate its effectiveness. METHODS: Patients were
      divided into three groups: those with faecal incontinence (A), constipation (B)
      or both (C). The Biotrol Irrimatic pump or the irrigation bag was used for
      colonic irrigation. Patients completed a questionnaire at baseline and after 3, 6
      and 12 months, as well as a Short Form 36 health survey and an American Society
      of Colon and Rectal Surgery quality of life questionnaire at baseline and after 6
      months. RESULTS: The study included 39 patients (26 women; mean age 58.0 years).
      In group A, 11 of 18 patients were pseudocontinent for faeces at 3 months (P <
      0.001). Parks' incontinence scores decreased for all patients in this group at 3
      months (P < 0.001), 6 months (P = 0.036) and 1 year (P = 0.005). In group B,
      three of ten patients reported a major improvement. The mean score for the
      feeling of incomplete evacuation decreased at 3 months (P = 0.007), 6 months (P =
      0.013) and 1 year (P = 0.036). In group C, six of ten patients became
      pseudocontinent for faeces (P = 0.009) and three reported improvement in
      constipation. The overall quality of life scores improved (P = 0.012).
      CONCLUSION: Retrograde colonic irrigation is an undervalued but effective
      alternative treatment for intractable defaecation disorders.

PMID- 18720455
TI  - Oestrogen receptor gene (ESR1) amplification is frequent in endometrial carcinoma
      and its precursor lesions.
AB  - Oestrogen receptor alpha (ER) plays a critical, diverse and not fully understood
      role in endometrial carcinoma. Most endometrial carcinomas express ER and some of
      these tumours respond favourably to anti-oestrogen therapy. On the other hand,
      tamoxifen therapy constitutes a major risk factor for endometrial carcinoma
      development. Amplification of the ESR1 gene encoding ER was recently shown to
      constitute a mechanism for ER over-expression in breast carcinoma. This study was
      designed to determine the potential role of ESR1 amplifications in endometrial
      carcinoma. Tissue microarrays of 368 endometrial carcinomas and large sections of
      43 cases of endometrial hyperplasia were analysed for ESR1 gene amplification and
      ER protein expression by means of fluorescence in situ hybridization (FISH) and
      immunohistochemistry. FISH revealed ESR1 amplification in 40/176 (23%) cancers,
      6/19 (32%) atypical complex hyperplasias, 3/10 (30%) complex hyperplasias without
      atypia and 2/14 (14%) simple hyperplasias without atypia. Strong ER protein
      expression was significantly linked to ESR1 amplification in endometrial
      carcinoma (p = 0.0036). These data indicate that ESR1 amplification might be one
      mechanism for ER over-expression in endometrial carcinoma, and suggest an early
      role for ESR1 amplification in the development of a significant fraction of
      endometrial carcinoma. Given the predictive role of ESR1 amplification for
      tamoxifen response in breast carcinoma, it will be interesting to investigate the
      response of ESR1-amplified endometrial cancers to anti-oestrogenic drugs.

PMID- 18720456
TI  - Screening and characterization of reactive metabolites using glutathione ethyl
      ester in combination with Q-trap mass spectrometry.
AB  - The present study describes a new analytical approach for the detection and
      characterization of chemically reactive metabolites using glutathione ethyl ester
      (GSH-EE) as the trapping agent in combination with hybrid triple quadrupole
      linear ion trap mass spectrometry. Polarity switching was applied between a
      negative precursor ion (PI) survey scan and the positive enhanced product ion
      (EPI) scan. The negative PI scan step was carried out monitoring the anion at m/z
      300, corresponding to deprotonated gamma-glutamyl-dehydroalanyl-glycine ethyl
      ester originating from the GSH-EE moiety. Samples resulting from incubations in
      the presence of GSH-EE were cleaned and concentrated by solid-phase extraction,
      followed by the PI-EPI analysis. Unambiguous identification of GSH-EE-trapped
      reactive metabolites was greatly facilitated by the unique survey scan of the
      anion at m/z 300, which achieved less background interference, in particular,
      from endogenous glutathione adducts present in human liver microsomes. Further
      structural characterization was achieved by analyzing positive MS(2) spectra that
      featured rich fragments without mass cutoff and were acquired in the same liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The effectiveness
      and reliability of this approach was evaluated using a number of model compounds
      in human liver microsomal incubations, including acetaminophen, amodiaquine,
      carbamazepine, 4-ethylphenol, imipramine and ticlopidine. In addition,
      iminoquinone reactive metabolites of mianserin were trapped and characterized for
      the first time using this method. Compared to neutral loss (NL) scanning assays
      using GSH as the trapping agent, the results have demonstrated superior
      selectivity, sensitivity, and reliability of this current approach.

PMID- 18720457
TI  - Refinement of breast cancer classification by molecular characterization of
      histological special types.
AB  - Most invasive breast cancers are classified as invasive ductal carcinoma not
      otherwise specified (IDC NOS), whereas about 25% are defined as histological
      'special types'. These special-type breast cancers are categorized into at least
      17 discrete pathological entities; however, whether these also constitute
      discrete molecular entities remains to be determined. Current therapy decision
      making is increasingly governed by the molecular classification of breast cancer
      (luminal, basal-like, HER2+). The molecular classification is derived from mainly
      IDC NOS and it is unknown whether this classification applies to all histological
      subtypes. We aimed to refine the breast cancer classification systems by
      analysing a series of 11 histological special types [invasive lobular carcinoma
      (ILC), tubular, mucinous A, mucinous B, neuroendocrine, apocrine, IDC with
      osteoclastic giant cells, micropapillary, adenoid cystic, metaplastic, and
      medullary carcinoma] using immunohistochemistry and genome-wide gene expression
      profiling. Hierarchical clustering analysis confirmed that some histological
      special types constitute discrete entities, such as micropapillary carcinoma, but
      also revealed that others, including tubular and lobular carcinoma, are very
      similar at the transcriptome level. When classified by expression profiling, IDC
      NOS and ILC contain all molecular breast cancer types (ie luminal, basal-like,
      HER2+), whereas histological special-type cancers, apart from apocrine carcinoma,
      are homogeneous and only belong to one molecular subtype. Our analysis also
      revealed that some special types associated with a good prognosis, such as
      medullary and adenoid cystic carcinomas, display a poor prognosis basal-like
      transcriptome, providing strong circumstantial evidence that basal-like cancers
      constitute a heterogeneous group. Taken together, our results imply that the
      correct classification of breast cancers of special histological type will allow
      a more accurate prognostication of breast cancer patients and facilitate the
      identification of optimal therapeutic strategies.

PMID- 18720458
TI  - Mass spectrometry in biodefense.
AB  - Potential agents for biological attacks include both microorganisms and toxins.
      In mass spectrometry (MS), rapid identification of potential bioagents is
      achieved by detecting the masses of unique biomarkers, correlated to each agent.
      Currently, proteins are the most reliable biomarkers for detection and
      characterization of both microorganisms and toxins, and MS-based proteomics is
      particularly well suited for biodefense applications. Confident identification of
      an organism can be achieved by top-down proteomics following identification of
      individual protein biomarkers from their tandem mass spectra. In bottom-up
      proteomics, rapid digestion of intact protein biomarkers is again followed by
      MS/MS to provide unambiguous bioagent identification and characterization.
      Bioinformatics obviates the need for culturing and rigorous control of
      experimental variables to create and use MS fingerprint libraries for various
      classes of bioweapons. For specific applications, MS methods, instruments and
      algorithms have also been developed for identification based on biomarkers other
      than proteins and peptides.

PMID- 18720459
TI  - Gland-preserving surgery for pleomorphic adenoma in the submandibular gland.
AB  - BACKGROUND: Removal of tumours arising in the submandibular gland (SMG) usually
      involves excision of the entire gland. This prospective study evaluated the
      efficacy of gland-preserving surgery in patients with benign SMG tumours.
      METHODS: Twenty consecutive patients with pleomorphic adenomas in the SMG
      underwent local excision of tumours with limited tumour-free margins and
      preservation of the remnant glandular tissues. All patients had salivary
      scintigraphy before and 6 months after surgery, with ultrasonography 2 years
      after operation. Complications, operating time, salivary function and rates of
      tumour recurrence were evaluated. RESULTS: The mean operating time was 28 min,
      and no patient had neurological complications. After surgery, the function of the
      affected gland was equal to that of the unaffected gland. All patients had
      symmetrical facial contours without defects in the operated submandibular
      triangle. None of the patients had evidence of tumour recurrence on
      ultrasonographic examination and regular clinical examination at a median of 36
      months after surgery. CONCLUSION: Gland-preserving surgery in patients with
      benign SMG tumours preserves salivation, and reduces surgical morbidity and
      operating time, with good cosmesis but without compromising local control.

PMID- 18720461
TI  - Epidemiology, risk and prognostic factors in mesenteric venous thrombosis.
AB  - BACKGROUND: Epidemiological reports on risk and prognostic factors in patients
      with mesenteric venous thrombosis (MVT) are scarce. METHODS: Patients with MVT
      were identified through the inpatient and autopsy registry between 2000 and 2006
      at Malmo University Hospital. RESULTS: Fifty-one patients had MVT, diagnosed at
      autopsy in six. The highest incidence (11.3 per 100,000 person-years) was in the
      age category 70-79 years. Activated protein C resistance was present in 13 of 29
      patients tested. D-dimer at admission was raised in all five patients tested.
      Multidetector row computed tomography (CT) in the portal venous phase was
      diagnostic in all 20 patients investigated, of whom 19 were managed
      conservatively. The median length of resected bowel in 12 patients who had
      surgery was 0.6 (range 0.1-2.2) m. The overall 30-day mortality rate was 20
      percent; intestinal infarction (P = 0.046), treatment on a non-surgical ward (P =
      0.001) and CT not done (P = 0.022) were associated with increased mortality.
      Cancer was independently associated with long-term mortality: hazard ratio 4.03,
      95 percent confidence interval 1.03 to 15.85; P = 0.046. CONCLUSION: Portal
      venous phase CT appeared sensitive in diagnosing MVT. As activated protein C
      resistance was a strong risk factor, lifelong anticoagulation should be
      considered.

PMID- 18720460
TI  - Plasminogen activator, but not systemic antibiotic therapy, prevents abscess
      formation in an experimental model of secondary peritonitis.
AB  - BACKGROUND: Intra-abdominal abscesses are sources of recurrent or ongoing
      abdominal sepsis. They are an important target for prevention and treatment
      during or after surgical treatment of peritonitis. Experimental data suggest that
      fibrinolytic therapy may be effective when antibiotics are not. METHODS:
      Peritonitis was induced via intra-abdominal injection of a faeces and bacteria
      mixture in male Wistar rats. Surgical debridement was performed after 1 h. Next
      to untreated controls, animals were treated with antibiotics (ceftriaxone plus
      metronidazole), recombinant tissue plasminogen activator (rtPA) or both.
      Abdominal fluid samples were taken at 24, 72 and 120 h for interleukin 6,
      interleukin 10 and tumour necrosis factor alpha measurements and cell counts.
      After 5 days the abdomen was inspected for the presence of abscesses. RESULTS:
      Antibiotics did not significantly affect abscess formation. However, giving rtPA
      significantly reduced the number of rats with abscesses and the abscess load per
      rat, both in the absence and presence of concomitant antibiotic therapy. No
      adverse side-effects were observed and no meaningful differences in the local
      inflammatory response were found. CONCLUSION: In this rat model, rtPA
      consistently reduced abscess formation after surgical treatment of secondary
      peritonitis. It therefore represents a promising adjuvant to conventional
      therapy.

PMID- 18720462
TI  - Leucocyte and platelet adhesion in different layers of the small bowel during
      experimental total warm ischaemia and reperfusion.
AB  - BACKGROUND: Ischaemia and reperfusion (IR) of the small bowel is involved in many
      clinical conditions. A key component in IR-induced tissue damage is microvascular
      dysfunction. The aim was to investigate the role of leucocytes and platelets in
      capillary flow impediment and tissue damage. METHODS: Anaesthetized rats were
      subjected to 30 min warm ischaemia of the small bowel, followed by 1 h
      reperfusion. To elucidate the influence of leucocytes on platelet adhesion,
      leucocyte-vessel wall interactions induced by IR were prevented by anti-platelet
      activating factor (PAF) or anti-intercellular adhesion molecule (ICAM)-1.
      Intravital videomicroscopy was performed and tissue injury was evaluated
      histologically. RESULTS: In submucosal venules, IR induced an increase in the
      median number of interacting leucocytes from 3 to 10 and 20 leucocytes per 100
      microm venule segment after 10 and 60 min reperfusion respectively. Anti-PAF or
      anti-ICAM-1 completely attenuated this increase, resulting in an eightfold
      improvement in submucosal capillary flow and reduced tissue injury. Shedding of
      villi no longer occurred. Platelet-vessel wall interactions occurred particularly
      in submucosal venules, but were not affected by anti-PAF or anti-ICAM-1.
      CONCLUSION: Small bowel IR initiated an inflammatory and thrombotic response in
      the submucosal layer only. Attenuation of leucocyte adhesion improved submucosal
      capillary perfusion, preventing shedding of mucosal villi.

PMID- 18720463
TI  - Clinical, physiological and radiological assessment of rectovaginal septum
      reinforcement with mesh for complex rectocele.
AB  - BACKGROUND: Rectocele can be part of a more complex rectal prolapse syndrome
      including rectal intussusception and enterocele. This reflects insufficiency at
      different levels of support in the posterior pelvic compartment. A new technique
      involving reinforcement of the rectovaginal septum with mesh by a combined
      laparoscopic and perineal approach was evaluated. METHODS: The study included 18
      patients with a complex rectocele and grade 2-3 rectal intussusception and
      enterocele (eight patients). Patients had clinical, physiological and
      radiological follow-up. RESULTS: There was no major perioperative morbidity and
      mean hospital stay was 4.5 (range 3-7) days. After a mean of 24.2 (range 13-35)
      months there was no clinical recurrence of rectocele. Symptoms of obstructed
      defaecation resolved in 14 of 17 patients. The Patient Assessment of Constipation
      Symptoms score decreased from a mean(s.d.) of 12.6(5.9) to 3.9(4.2), and a
      rectocele symptom score from 14.3(3.3) to 2.3(2.8). No new-onset constipation,
      urge or faecal incontinence nor new-onset dyspareunia was reported. Radiological
      investigation in eight patients revealed a sufficient anatomical repair at the
      different levels of support. A slight decrease in rectal compliance was measured,
      with no significant reduction in rectal capacity. CONCLUSION: Complete
      rectovaginal septum reinforcement with mesh corrected complex rectoceles, with
      good functional outcome.

PMID- 18720464
TI  - 1H-17O nuclear quadrupole double resonance in phenylphosphinic acid and
      phenylphosphonic acid. 17O quadrupole coupling in P = O and P-O-H bonds.
AB  - The (17)O nuclear quadrupole resonance (NQR) frequencies have been measured in
      phenylphosphinic acid and phenylphosphonic acid using nuclear quadrupole double
      resonance. The quadrupole coupling constants have been determined with an
      uncertainty of +/- 10 kHz and the asymmetry parameter eta with an uncertainty of
      +/- 0.01. The results are compared to the published results of the theoretical
      calculation and the high-field solid-state NMR measurements. The position of
      hydrogen in the O-H...O hydrogen bond in phenylphosphinic acid has also been
      determined. On the basis of the present and the previously published data we show
      that the principal values of the electric-field-gradient tensor in P = O and P-O
      H bonds correlate. A correlation between the nuclear quadrupole parameters and
      the length of the P-O bond is also observed.

PMID- 18720468
TI  - Applications of silver nanoparticles capped with different functional groups as
      the matrix and affinity probes in surface-assisted laser desorption/ionization
      time-of-flight and atmospheric pressure matrix-assisted laser
      desorption/ionization ion trap mass spectrometry for rapid analysis of sulfur
      drugs and biothiols in human urine.
AB  - A strategy is presented for the analysis of sulfur drugs and biothiols using
      silver nanoparticles (AgNPs) capped with different functional groups as the
      matrix and affinity probes in surface-assisted laser desorption/ionization time
      of-flight mass spectrometry (SALDI-TOF MS) and atmospheric pressure-matrix
      assisted laser desorption/ionization ion trap mass spectrometry (AP-MALDI-ITMS).
      Biothiols adsorbed on the surface of AgNPs through covalent bonding were
      subjected to ultraviolet (UV) radiation that enabled desorption and ionization
      due to the excellent photochemical property of NPs. The proposed method has been
      successfully applied for the determination of cysteine and homocysteine in human
      urine samples using an internal standard. The limit of detection (LOD) and limit
      of quantification (LOQ) for cysteine and homocysteine in urine sample are 7 and
      22 nM, respectively, with a relative standard deviation (RSD) of <10%. The
      advantages of the present method compared with the methods reported in the
      literature for biothiol analysis are simplicity, rapidity and sensitivity without
      the need for time-consuming separation and tedious preconcentration processes.
      Additionally, we also found that the bare AgNPs can be directly used as the
      matrix in MALDI-TOF MS for the analysis of sulfur drugs without the addition of
      an extra proton source.

PMID- 18720469
TI  - Early results from a randomized clinical trial of colon J pouch versus transverse
      coloplasty pouch after low anterior resection for rectal cancer.
AB  - BACKGROUND: Patients with primary rectal cancer undergoing low anterior resection
      are often reconstructed using a pouch procedure. The aim of this trial was to
      compare colon J pouch (CJP) with transverse coloplasty pouch (TCP) reconstruction
      with regard to functional results, perioperative mortality and morbidity. As
      there is considerable uncertainty over the true anastomotic leak rate in patients
      with a TCP, the study analysed short-term outcome data. METHODS: Elective
      patients suitable for either procedure after sphincter-saving low anterior
      resection were eligible. Randomization took place during surgery. The primary
      endpoint was the rate of late evacuation problems after 2 years; secondary
      endpoints were anastomotic leak rate, perioperative morbidity and mortality.
      RESULTS: Between 21 October 2002 and 5 December 2005, 149 patients were
      randomized. All 76 patients randomized to TCP had the procedure compared with 68
      of the 73 patients (93 percent) randomized to CJP. Both groups were comparable
      with regard to demographic and clinical characteristics. Surgical complications
      (CJP: 19 percent; TCP: 18 percent) and the overall anastomotic leak rate (8
      percent) were equally distributed in both groups. CONCLUSION: This trial
      demonstrated a comparable early outcome for TCP and CJP. This contradicts
      previous reports suggesting a higher leak rate after TCP. REGISTRATION NUMBER:
      ISRCTN78983587 (http://www.controlled-trials.com).

PMID- 18720470
TI  - Gas chromatography/time-of-flight mass spectrometry based metabonomic approach to
      differentiating hypertension- and age-related metabolic variation in
      spontaneously hypertensive rats.
AB  - Metabonomics is a systematic approach to the study of in vivo metabolic profiles
      and therefore allows deep insight into and a better understanding of the
      pathogenesis of disease. To characterize the development of hypertension, a
      hypertensive animal model, the spontaneously hypertensive rat (SHR), and its
      normotensive control, the Wistar Kyoto (WKY) rat, were investigated and their
      blood plasma analyzed using the high-throughput metabolomic tool, gas
      chromatography/time-of-flight mass spectrometry (GC/TOFMS). A total of 187 peaks
      were quantitatively determined after deconvolution, and 78 of them were
      identified. Principal components analysis (PCA) and projection to latent
      structure partial least-squares discriminant analysis (PLS-DA) were used to
      process the GC/TOFMS data. The resulting mathematical models were further
      validated by cross-validation. Plasma compositional differences of many
      identified compounds showed hypertension-related variation between SHR and WKY
      rats, and age-related changes from 10 to 18 weeks for both the SHR and WKY rats.
      These compositional changes involved compounds such as hexadecanoic acid,
      linoleic acid, oleic acid, stearic acid, 3-hydroxybutyric acid, citric acid,
      threonic acid, tyrosine, tryptophan, threonine, phenylalanine, serine, ornithine,
      methionine, 3-hydroxyproline, creatinine, erythrose, myo-inositol, D
      methylglucopyranoside, tocopherol, sitosterol, and nonesterified cholesterol.
      Significantly elevated free fatty acids (FFA) were observed in SHR relative to
      those in WKY rats, and their levels increased as the SHR aged from 10 to 18
      weeks. The close correlation between FFA and hypertension suggests that FFA are
      potential biomarker candidates for hypertension and they may play an important
      role in the development of hypertension in SHR. It is also indicated that
      GC/TOFMS-based metabonomics is a powerful approach to identifying potential
      biomarkers and investigating the pathological processes of hypertension and the
      physiological developments of aging.

PMID- 18720471
TI  - MAGI2 genetic variation and inflammatory bowel disease.
AB  - BACKGROUND: Despite recent advances the majority of inflammatory bowel disease
      (IBD) susceptibility 'genes' remain undiscovered. Recent data suggest that
      autoimmune conditions may 'share' susceptibility loci. Epidemiological evidence
      indicates an association between celiac disease and IBD and both conditions
      demonstrate increased gut permeability. MAGI2, recently implicated in ulcerative
      colitis (UC) and celiac disease, encodes a scaffolding protein involved in
      epithelial integrity. Our aim was to test MAGI2 variants for association with IBD
      and also their role in determining intermediate hereditary phenotypes defined by
      antibody production to microbial antigens. METHODS: We genotyped 113 MAGI2 single
      nucleotide polymorphisms (SNPs) in 681 cases of Crohn's disease (CD), 259 UC
      cases, and 195 controls. RESULTS: The most significant IBD association was in
      intron 6 (rs2160322, P = 0.009) and both UC (P = 0.006) and CD (P = 0.03)
      contributed to this association. The most significant CD association was with an
      intron 2 haplotype (rs7785088/rs323149/rs13246026, P = 0.002). We observed highly
      significant associations with UC in intron 6 (rs7803276/rs7803705, P = 0.002) and
      also significant associations in introns 2, 6, and 20. Significant associations
      were seen with: immunoglobulin G (IgG) anti-Saccharomyces cerevisiae antibodies
      (ASCA)-positive CD in intron 3 (P = 0.003), intron 6 (P = 0.003), and intron 20
      (P = 0.001); anti-CBir1-positive CD in intron 3 (P = 0.0001) and intron 6 (P =
      0.008); and anti-outer membrane porin C (OmpC)-positive CD in intron 3 (P =
      0.0009), and intron 9 (P = 0.007). Quantitative antibody levels were also
      associated with variants in intron 4 (anti-IgA ASCA, P = 0.0003 and anti-IgG
      ASCA, P = 0.0002). CONCLUSIONS: These findings support the significance of the
      epithelial barrier in IBD pathogenesis.

PMID- 18720472
TI  - Birth outcomes in women with eating disorders in the Norwegian Mother and Child
      cohort study (MoBa).
AB  - OBJECTIVE: We explored the impact of eating disorders on birth outcomes in the
      Norwegian Mother and Child Cohort Study. METHOD: Of 35,929 pregnant women, 35
      reported broad anorexia nervosa (AN), 304 bulimia nervosa (BN), 1,812 binge
      eating disorder (BED), and 36 EDNOS-purging type (EDNOS-P) in the six months
      before or during pregnancy. The referent comprised 33,742 women with no eating
      disorder. RESULTS: Pre-pregnancy body mass index (BMI) was lower in AN and higher
      in BED than the referent. AN, BN, and BED mothers reported greater gestational
      weight gain, and smoking was elevated in all eating disorder groups. BED mothers
      had higher birth weight babies, lower risk of small for gestational age, and
      higher risk of large for gestational age and cesarean section than the referent.
      Pre-pregnancy BMI and gestational weight gain attenuated the effects. CONCLUSION:
      BED influences birth outcomes either directly or via higher maternal weight and
      gestational weight gain. The absence of differences in AN and EDNOS-P may reflect
      small numbers and lesser severity in population samples. Adequate gestational
      weight gain in AN may mitigate against adverse birth outcomes. Detecting eating
      disorders in pregnancy could identify modifiable factors (e.g., high gestational
      weight gain, binge eating, and smoking) that influence birth outcomes.

PMID- 18720474
TI  - Are single-parent families different from two-parent families in the treatment of
      adolescent bulimia nervosa using family-based treatment?
AB  - OBJECTIVE: To examine whether family-based treatment (FBT) for adolescent bulimia
      nervosa (BN), which emphasizes family involvement in helping to reduce binge
      eating and purging behaviors, is differentially efficacious in single-parent
      families versus two-parent families. METHOD: Forty-one adolescents (97.6% female;
      16.0 +/- 1.7 years old) with either BN (n = 18) or subthreshold BN (n = 23) were
      randomized to FBT as part of a larger randomized controlled trial studying
      treatments for adolescent BN. RESULTS: Two-parent (n = 27; 65.9%) and single
      parent (n = 14; 34.2%) families were compared on demographic variables, presence
      of comorbid psychiatric illnesses, and symptoms of BN at baseline, post, and 6
      month follow-up. ANOVA and chi-square analyses revealed no statistically
      significant differences between two-parent and single-parent families on any
      variables with the exception of ethnicity, for which a greater proportion of
      Caucasians and Hispanic families had two- parent families compared with African
      American families (chi(2) = 8.68, p = .01). DISCUSSION: These findings suggest
      that FBT may be an appropriate and efficacious treatment for single-parent
      families as well as two-parent families, despite the reliance on parental
      intervention to reduce bulimic symptoms and normalize eating patterns.

PMID- 18720473
TI  - A prospective study of loss of control eating for body weight gain in children at
      high risk for adult obesity.
AB  - OBJECTIVE: Limited data suggest that disordered-eating may predispose children to
      excessive weight gain. We investigated the relationship between baseline
      responses to the Eating Disorder Examination adapted for Children (ChEDE) and
      change in BMI (kg/m(2)) in children at high risk for adult obesity. METHOD:
      Children (6-12 years) were administered the ChEDE to assess loss of control (LOC)
      eating, dietary restraint, and eating, shape, and weight concern. Height and
      weight were measured at baseline and annually. RESULTS: Between July, 1999, and
      August, 2007, 772 measurements were obtained from 143 children over 4.5 +/- 1.9
      years. LOC eating predicted an increased rate of BMI growth over time (p = .02).
      Compared with children without LOC, those reporting LOC gained an additional mean
      2.4 kg of weight per year. CONCLUSION: LOC is a salient predictor of weight gain
      during middle childhood. Interventions that decrease LOC eating should be
      evaluated for their ability to prevent excessive pediatric weight gain.

PMID- 18720475
TI  - Informing family approaches to eating disorder prevention: perspectives of those
      who have been there.
AB  - OBJECTIVE: The study explored how aspects of the family environment may relate to
      the onset of eating disorders. METHOD: Semi-structured interviews were conducted
      with 27 individuals currently receiving treatment for eating disorders. Data were
      analyzed using principles of content analysis. RESULTS: Eight themes emerged
      regarding recommendations for families to prevent the onset of eating disorders:
      (1) Enhance parental support; (2) Decrease weight and body talk; (3) Provide a
      supportive home food environment; (4) Model healthy eating habits and physical
      activity patterns; (5) Help your children build self-esteem beyond looks and
      physical appearance; (6) Encourage appropriate expression of feelings and use of
      coping mechanisms; (7) Increase your understanding of eating disorder signs and
      symptoms; and (8) Gain support in dealing appropriately with your own struggles.
      DISCUSSION: Our results can be utilized to generate new theoretical insights as
      to how parents can raise children with healthy weight-related attitudes and
      behaviors.

PMID- 18720477
TI  - A critique of the false-positive report probability.
AB  - The false positive report probability (FPRP) was proposed as a Bayesian
      prophylactic against false reports of significant associations. Unfortunately,
      the derivation of the FPRP is unsound. A heuristic derivation fails to make its
      point, and a formal derivation reveals a probabilistic misrepresentation of an
      observation. As a result, the FPRP can yield serious inferential errors. In
      particular, the FPRP can use an observation that is many times more likely under
      the null hypothesis than under the alternative to infer that the null hypothesis
      is far less probable than the alternative. Contrary to its intended purpose, the
      FPRP can promote false positive results. It should not be used. A modified FPRP
      is derived, but it appears to have limited application and does not address the
      problem of false reports of significant associations. The conditional error
      probability is a possible replacement for the FPRP.

PMID- 18720476
TI  - A new association test to test multiple-marker association.
AB  - As a result of the availability of a very large numbers of single nucleotide
      polymorphisms, there has been increasing interest in genetic associations
      involving several closely linked loci. Methods for detection of association
      between traits and multiple genetic polymorphisms are being rapidly developed,
      which include the Hotelling's T(2) test and the LD contrast (LDC) tests. The
      Hotelling's T(2) test can be considered as a test to compare the means of the
      genotypic score in cases and controls; while the (LDC) tests can be considered as
      a test to compare the variance-covariance matrices of the genotypic score in
      cases and controls. In this article, we propose a likelihood ratio test which
      simultaneously compares the means and the variance-covariance matrices of the
      genotypic score in cases and controls. We use simulation studies to evaluate the
      type I error rate of the proposed test, and compare the power of the test with
      the Hotelling's T(2) test and the LDC tests. The simulation results show that
      when marginal effects of the disease loci are strong, the proposed test is more
      powerful than the LDC tests and similar with or slightly less powerful than the
      Hotelling's T(2) test. If there are interaction effects and weak or no marginal
      effects, the proposed method is more powerful than the Hotelling's T(2) test and
      slightly more powerful than the LDC tests.

PMID- 18720478
TI  - Neonatal hypoxic/ischemic brain injury induces production of calretinin
      expressing interneurons in the striatum.
AB  - Ischemia-induced striatal neurogenesis from progenitors in the adjacent
      subventricular zone (SVZ) in young and adult rodents has been reported. However,
      it has not been established whether the precursors that reside in the SVZ retain
      the capacity to produce the full range of striatal neurons that has been
      destroyed. By using a neonatal rat model of hypoxic/ischemic brain damage, we
      show here that virtually all of the newly produced striatal neurons are
      calretinin (CR)-immunoreactive (+), but not DARPP-32(+), calbindin-D-28K(+),
      parvalbumin(+), somatostatin(+), or choline acetyltransferase(+). Retroviral fate
      mapping studies confirm that these newly born CR(+) neurons are indeed
      descendants of the SVZ. Our studies indicate that, although the postnatal SVZ has
      the capacity to produce a range of neurons, only a subset of this repertoire is
      manifested in the brain after injury.

PMID- 18720479
TI  - Risk of subsequent endometrial carcinoma associated with endometrial
      intraepithelial neoplasia classification of endometrial biopsies.
AB  - BACKGROUND: Histopathologic diagnosis of endometrial biopsies is used to estimate
      the risk of progression to carcinoma and guide clinical management. Problems with
      the widely used World Health Organization (WHO) system for classifying
      endometrial hyperplasia (EH) have prompted the development of an alternative
      system based on endometrial intraepithelial neoplasia (EIN). The authors
      estimated progression risk associated with EIN among endometrial biopsies in a
      nested case-control study of EH progression. METHODS: Index biopsies with
      original community pathology diagnoses of disordered proliferative endometrium
      (DPEM) or EH that were independently confirmed by a panel of pathologists were
      independently reviewed and assigned EIN classifications (inadequate, benign, EIN,
      or cancer) by a second panel of pathologists. Cases (N = 138) progressed to
      carcinoma at least 1 year (median, 6 years) after their index biopsy. Controls (N
      = 241) also had EH, did not progress to carcinoma, and were individually matched
      to cases based on age at EH, date of EH, and length of follow-up. By using
      conditional logistic regression, the authors estimated relative risks (RRs) with
      95% confidence intervals (95% CIs) for progression to carcinoma for EIN versus
      benign. RESULTS: In the EIN system, 71 (52.6%) cases and 159 (66.8%) controls
      were classified as benign and 42 (31.1%) cases and 65 (27.3%) controls were
      classified as EIN. The RR for EIN versus benign was 7.76 (95% CI, 3.36-17.91). In
      the WHO system, the RR for atypical hyperplasia (AH) versus DPEM, simple
      hyperplasia, or complex hyperplasia was 9.19 (95% CI, 3.87-21.83). CONCLUSIONS:
      Among women observed for at least 1 year after receiving a biopsy-based EH
      diagnosis, EIN and AH were both found to have similarly increased risks of
      progression to carcinoma.

PMID- 18720480
TI  - A phase 2 trial of sequential temozolomide chemotherapy followed by high-dose
      interleukin 2 immunotherapy for metastatic melanoma.
AB  - BACKGROUND: Previous biochemotherapy regimens for metastatic melanoma have
      required attenuated dosages of interleukin 2 (IL-2) that may have compromised
      efficacy. METHODS: In a phase 2 study, the authors tested sequential temozolomide
      (75 mg/m2 per day orally for 3 weeks) followed by high-dose, IL-2 (600,000 U/kg
      per dose intravenously; maximum, 14 doses over 5 days). RESULTS: Thirty-eight
      patients with treatment-naive American Joint Committee on Cancer stage IV
      melanoma (8 patients with M1a disease, 6 patients with M1b disease, and 24
      patients with M1c disease) were enrolled. Ten patients had a history of treated
      brain metastases. Thirty-one patients who received at least 2 cycles of IL-2 were
      evaluable for response. Grade 3 toxicities included hyperbilirubinemia (9
      patients), hematologic toxicities (leukopenia in 5 patients, thrombocytopenia in
      3 patients), diarrhea (2 patients), and oliguria (1 patient). One patient had
      grade 4 nausea. The overall response rate (ORR) was 16% and included 3 complete
      responses that lasted 10.8 months, > or =32 months, and > or =36 months and 2
      partial responses that lasted 13 months and 14 months. Responses were observed in
      patients with M1a disease and in patients with M1c disease. Sixteen patients had
      stable disease (15 patients progressed). The median progression-free survival
      (PFS) was 5.3 months (95% confidence interval [CI], 3.7-7.5 months). The
      probability of PFS at 6 months was 0.52 (95% CI, 0.33-0.67). Among 38 enrolled
      patients, 16 patients remained alive at a median follow-up of 6.7 months (range,
      1.9-36.1 months). The median overall survival (OS) was 12.1 months (95% CI, 9.1
      16.4 months), and the probability of 12-month OS was 0.54 (95% CI, 0.34-0.70
      months). CONCLUSIONS: The current results indicated that it is safe to administer
      HD IL-2 sequentially with temozolomide and that this combination has lower
      toxicity than previously used concurrent biochemotherapy regimens. However, The
      ORR and the durability of responses with this combination did not exceed those of
      single-agent HD IL-2.

PMID- 18720481
TI  - Preliminary evaluation of the toxicity of some synthetic furan derivatives in two
      cell lines and Artemia salina.
AB  - This study describes the preliminary toxicity evaluation of five new furan
      derivatives, 2-[2-acetylamino-2-[(benzothiazolyl-substituted)aminocarbonyl]vinyl]
      5-nitro furane (compounds A, B, D and E) and 2-[2-phenylamino-2
      [benzothiazolylaminocarbonyl]vinyl]furane (compound C). Cytotoxicity was
      determined using the MTT (tetrazolium salt) method over BHK21 (Syrian baby
      hamster kidney) and Hep-2 (human larynx carcinoma) cells, which had previously
      been used to evaluate the cytotoxicity of the 5-nitrofuran derivatives. The
      lethal concentration 50 (LC(50)) was determined using brine shrimp (Artemia
      salina) bioassay. Nitrofurantoin was used as reference compound. The results
      demonstrate that BHK21 cells are more sensitive than Hep-2 cells. This
      structurally related serial of compounds shows a differential toxicity, which is
      an indication that the toxicity naturally arising from the nitro group can be
      modulated by the substituents over the furan ring. Additionally, compound C, the
      only derivative with no nitro group, was least toxic to Hep-2, but exhibits
      toxicity to BHK21 cells and brine shrimp. The LC(50 )brine shrimp test (BST)
      bioassay results were as follows: A, 654.2 microg ml(-1); B, 50.0 microg ml(-1);
      C, 533.4 microg ml(-1); D, 172.1 microg ml(-1); E, 76.4 microg ml(-1), and NF,
      >1000 microg ml(-1).

PMID- 18720482
TI  - Interplay between acetate ions, peripheral groups, and reactivity of the core
      nitrogens in transmetalation of tetrapyrroles.
AB  - The mechanism of acetate-assisted transmetalation of tetrapyrroles was
      investigated in a model system consisting of chlorophyll a and copper(II) acetate
      in organic solvents by using a spectroscopic and kinetic approach. Surprisingly,
      acetate ions bind to the central Mg in chlorophyll much more strongly than do
      acetonitrile, methanol and even pyridine, one of the best ligands in
      chlorophyllic systems. This exceptionally strong non-symmetrical axial ligation
      of the central Mg by acetate causes its out-of-plane displacement and deformation
      of the tetrapyrrole ring, thus facilitating the interaction with an incoming CuII
      complex. This mechanism is controlled by a keto-enol tautomerism of the
      chlorophyll isocyclic ring. Additionally, depending on solvent, acetate activates
      the incoming metal ions. These new insights allow to suggest a mechanism for the
      acetate method of metal exchange in tetrapyrrolic macrocycles, which resembles
      biological insertion of metal ions into porphyrins. It also provides a guideline
      for the design of more efficient methods for the metalation of porphyrins and
      related macrocycles.

PMID- 18720483
TI  - Diphosphinine derivatives of terpyridine: a new class of neutral pi-accepting PNP
      pincer ligands.

PMID- 18720484
TI  - Modular syntheses of diversonol-type tetrahydroxanthone mycotoxins: blennolide C
      (epi-hemirugulotrosin A) and analogues.

PMID- 18720485
TI  - Targeting the open-flap conformation of HIV-1 protease with pyrrolidine-based
      inhibitors.
AB  - HIV protease is a well-established drug target in antiviral chemotherapy. Immense
      research efforts have been made to discover effective inhibitors, thus making the
      enzyme one of the most studied and best characterized proteins. Although the
      protease exhibits high flexibility, all approved drugs target virtually the same
      protein conformation. The development of viral cross-resistance demands the
      generation of inhibitors with novel scaffolds and deviating modes of binding.
      Herein we report the design and the short, high-yielding stereoselective
      synthesis of a series of chiral, symmetric pyrrolidine-based inhibitors targeting
      the open-flap conformation of the protease. The obtained co-crystal structure
      with one derivative provides a valuable starting point for further inhibitor
      design.

PMID- 18720486
TI  - Anti-inflammatory activity of a new class of nitric oxide synthase inhibitors
      that release nitric oxide.
AB  - Nitric oxide (NO) is a gaseous mediator that exerts key regulatory functions in
      mammalian cells. Low levels of NO exert homeostatic functions and counteract
      inflammation, whereas high amounts of NO cause tissue destruction and cellular
      death. Herein we describe a new class of nitric oxide synthase (NOS) inhibitor NO
      donating drugs (NI-NODs). Human endothelial cells and human monocyte-based
      activity screening showed that NI-NODs inhibit IL-1beta production, modulate
      PGE(2) production, and protect against apoptosis. In a rodent model of colitis,
      NI-NOD1 and NI-NOD2 potently decreased inflammation. These data show that NI-NODs
      are effective in both in vitro and in vivo models of inflammation, mimicking the
      positive effects of low levels of NO and suppressing NOS-induced NO production.

PMID- 18720487
TI  - Intervening sequences in 23S rRNA genes and 23S rRNA fragmentation in Taylorella
      asinigenitalis UCD-1(T) strain.
AB  - PCR was performed with Taylorella asinigenitalis UCD-1(T) using two primer pairs
      constructed in silico for the amplification of the intervening sequences (IVSs)
      in the first quarter and central regions of the 23S rRNA gene. Following TA
      cloning and sequencing, the strain was identified to carry heterogeneous and
      multiple IVSs. Two similar tandem repeat units of 25 and 24 base pairs (bp) with
      unknown function(s) were identified within the two IVSs in the central region.
      Secondary structure models of IVSs, containing stem and loop structures, were
      demonstrated. Although 16S rRNA and 4-5S RNA species were identified in the
      purified RNA fraction, no 23S rRNAs were evident, resulting in the occurrence of
      some smaller RNA fragments from approximately 500 to 1,600 bp, in length. Thus,
      the 23S rRNA primary transcripts may be cleaved into some smaller fragments and
      IVSs. No IVS transcript was detected by northern blot hybridization analysis. The
      present and previous results strongly demonstrate the occurrence of heterogeneous
      and multiple IVSs in 23S rRNA gene sequences and 23S rRNA fragmentation, in T.
      asinigenitalis.

PMID- 18720488
TI  - In vitro antifungal activity and mechanism of action of chitinase against four
      plant pathogenic fungi.
AB  - To determine why chitinase has different antifungal activity on different
      pathogenic fungi in vitro, we purified recombinant rice chitinase from Pichia
      pastoris and investigated its antifungal activity against four fungi - Rhizopus
      stolonifer (Ehrenb. et Fr.) Vuill, Botrytis squamosa Walker, Pythium
      aphanidermatum (eds.) Fitzp, and Aspergillus niger van Tiegh. Scanning electron
      microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to
      analyze the surface microstructure and proportion of chitin in the cell wall of
      the four fungi, respectively. The results showed that the chitinase exhibited
      different antifungal activities against the four fungi, which was directly
      correlated to the surface microstructure and the proportion of chitin in the
      fungal cell wall. It will help understanding the antifungal mechanism of the
      recombinant chitinase and further determining its application scope on crop
      protection and post-harvest storage of fruits and vegetables.

PMID- 18720489
TI  - The surface layer protein of Bacillus thuringiensis CTC forms unique
      intracellular parasporal inclusion body.
AB  - Bacillus thuringiensis subsp. finitimus strain CTC forms round parasporal
      inclusion body. The inclusion body protein gene ctc has been cloned and
      characterized. Sequence homology analysis reveals that the amino acid sequence of
      CTC protein shows 87% identity with the surface layer (S-layer) protein Sap
      (GenBank Z36946) in B. anthracis. In this report, transmission electron
      microscope observation showed that CTC formed intracellular parasporal inclusion
      body and sheet structure of S-layer-like protein at the spore phase. Furthermore,
      the ctc gene was transformed into an acrystalliferous B. thuringiensis strain
      BMB171. The resulting transformant could form parasporal body which had the same
      shape and molecular weight of protein with that of B. thuringiensis CTC. These
      results, together with the sequence homology analysis of ctc gene, confirmed that
      the unique intracellular parasporal inclusion body of B. thuringiensis was
      comprised of S-layer protein.

PMID- 18720490
TI  - Detection by PCR of adhesins genes and slime production in clinical
      Staphylococcus aureus.
AB  - The presence of the ica loci and adhesins genes in clinical Staphylococcus aureus
      strains were considered important factors of virulence. In this study, 46 strains
      of Staphylococcus aureus were isolated from auricular infection, and were
      investigated for slime production using Congo Red Agar method (CRA). In order to
      detect the adhesins genes (ica A, ica D, fnb A, cna, Clf A) Polymerase Chain
      Reaction was used. Qualitative biofilm production of S. aureus using CRA plates
      revealed that 56.5% of strains were slime producers. In addition 78.26% of
      strains were ica A and ica D positive. While the fnbA gene was present in 76.1%
      of isolated strains. Furthermore, 56.5% of strains have the cna gene and 30.4%
      were clfA positives. Overall this study confirms the presence of fnb A and ica
      A/ica D genes in the majority of studies S. aureus strains isolated from
      Staphylococcal sepsis.

PMID- 18720491
TI  - Direct detection of Kitasatospora species with a chaperone oligonucleotide
      microarray method lacking PCR amplification.
AB  - Identification of members of the genus Kitasatospora from soil samples has been
      introduced to evaluate occurrence of potential natural compound producers in
      different habitats. The microarray hybridization usually involves PCR
      amplification of the target DNA. Since PCR might lead to biased amplification, a
      diagnostic Kitasatospora microarray technique was improved by a protocol lacking
      PCR amplification prior to hybridization. The described advanced hybridization
      method used chaperone oligonucleotides for direct co-hybridization with genomic
      DNA on an oligonuclotide microarray with optical readout.

PMID- 18720492
TI  - Photocontrolled cell adhesion on a surface functionalized with a caged arginine
      glycine-aspartate peptide.

PMID- 18720494
TI  - Saturation transfer difference (STD) NMR spectroscopy characterization of dual
      binding mode of a mannose disaccharide to DC-SIGN.

PMID- 18720495
TI  - Why do cationic hydridoiridium(III) complexes with beta-aminophosphane ligands
      favour the transfer hydrogenation of ketones over the direct "H2-hydrogenation"?-
      A computational approach.
AB  - Density functional theory and ab initio molecular orbital calculations show that
      the observed inability of cationic hydridoiridium(III) complexes with beta
      aminophosphane ligands to catalyse the direct hydrogenation of carbonyl compounds
      with dihydrogen ("H2-hydrogenation") in contrast to their ruthenium(II)
      equivalents is due to the inability of H2 to displace a coordinated solvent
      molecule from an intermediate hydrido complex.

PMID- 18720493
TI  - S-Adenosyl-L-methionine hydrolase (adenosine-forming), a conserved bacterial and
      archaeal protein related to SAM-dependent halogenases.

PMID- 18720497
TI  - Combination of lacunary polyoxometalates and high-nuclear transition metal
      clusters under hydrothermal conditions: IX. a series of novel polyoxotungstates
      sandwiched by octa-copper clusters.
AB  - The reaction of CuCl(2).2 H2O with trivacant Keggin polyoxoanions K8Na2[A-alpha
      GeW9O34].25 H2O or K10[A-alpha-SiW9O34].25 H2O in the presence of 1,2
      diaminopropane (dap), ethylenediamine (en) or 2,2'-bipyridine (2,2'-bpy) under
      hydrothermal conditions afforded five novel hybrid inorganic-organic octa-Cu
      sandwiched polyoxotungstates (POTs): H4[CuII8(dap)4(H2O)2(B-alpha-GeW9O34)2].13
      H2O (1), (H2en)2[CuII8-(en)4(H2O)2(B-alpha-GeW9O34)2].5 H2O(2),
      (H2en)2[CuII8(en)4(H2O)2(B-alpha-SiW9-O34)2].8 H2O (3), [CuII(H2O)2]H2[CuII8
      (en)4(H2O)2(B-alpha-SiW9O34)2] (4), and [CuII2(H2O)2(2,2'-bpy)2]{[CuII(bdyl)]2
      [CuII8(2,2'-bpy)4(H2O)2(B-alpha-GeW9-O34)2]}.4 H2O (bdyl=2,2'-bipyridinyl)(5).
      Additionally, CuCl(2).2 H2O reacts with the mixture of GeO2, Na2WO(4).2 H2O,
      H2SiW12O(40).2 H2O in the presence of 2,2'-bpy and 4,4'-bpy under hydrothermal
      conditions leading to another novel mixed-valent octa-Cu sandwiched POT hybrid:
      [CuI(2,2'-bpy)(4,4'-bpy)]2[{CuI2(2,2'-bpy)2(4,4'-bpy)]2[CuI2CuII6(2,2'-bpy)2(4,4'
      bpy)2(B-alpha-GeW9O34)2}].2 H2O (6). 1, 2, and 3 are discrete dimers constructed
      from two trivacant Keggin [B-alpha-XW9O34]10- (X=GeIV/SiIV) fragments and an octa
      Cu cluster whereas 4 displays the 3D (3,6)-connected nets with
      (4.6(2))(4(2).6(4).8(7).10(2)) topology, which are built by octa-Cu sandwiched
      polyoxometalate building blocks through copper cation bridges. 5 is a novel 2D
      layer based on octa-Cu sandwiched POT clusters and [CuII2(bdyl)] units.
      Interestingly, the rollover metalation of 2,2'-bpy is firstly observed in the
      system containing the copper complex under hydrothermal conditions. 6 is a
      discrete mixed-valent octa-Cu sandwiched POT supported by two CuI-complexes [CuI2
      (2,2'-bpy)2(4,4'-bpy)]2+ through 4,4'-bpy bridges, which constructs a novel
      dodeca-copper cluster. Notably, the octa-Cu cluster in 6 is mixed-valent and is
      different from those in 1-5. To our knowledge, 1-6 represent a rare family of
      POTs incorporating novel octa-nuclear transition-metal clusters in
      polyoxometalate chemistry. They were structurally characterized by FT-IR spectra,
      elemental analysis, thermogravimetric analysis, and single-crystal X-ray
      diffraction. The magnetic properties of 1, 4, and 5 were quantitatively analyzed
      by the MAGPACK software package.

PMID- 18720496
TI  - Palladium-based telomerization of 1,3-butadiene with glycerol using methoxy
      functionalized triphenylphosphine ligands.
AB  - Glycerol is considered a potential renewable building block for the synthesis of
      existing as well as new chemicals. A promising route is the telomerization of 1,3
      butadiene with glycerol leading to C8 chain ethers of glycerol with applications
      in, for example, surfactant chemistry. Recently, we reported a new set of
      palladium-based homogeneous catalytic systems for the telomerization of 1,3
      butadiene with glycerol and found that palladium complexes bearing methoxy
      functionalized triphenylphosphine ligands are highly active catalysts capable of
      converting crude glycerol without any significant loss of activity. Herein, we
      present a detailed account of these investigations by reporting on the influence
      of the butadiene/glycerol ratio, temperature, and reaction time on product
      selectivity and activity allowing further optimization of catalyst performance.
      Maximum activity and yield were reached for high 1,3-butadiene/glycerol ratios at
      a temperature of 90 degrees C, whereas the selectivity for mono- and diethers of
      glycerol could be optimized by combining high reaction temperatures and short
      reaction times with low butadiene/glycerol ratios. Variation of the PdII metal
      precursors and the metal/ligand ratio showed that palladium precursors with
      halogen ligands gave unsatisfying results, in contrast to precursors with weakly
      coordinated ligands such as [Pd(OAc)2] and [Pd(acac)2]. [Pd(dba)2], the only Pd0
      precursor tested, gave the best results in terms of activity, which illustrates
      the importance of the ability to form a Pd0 species in the catalytic cycle.
      Finally, base addition resulted in a shortening of the reaction time and most
      likely facilitates the formation of a Pd0 species. Based on these results, we
      were able to realize the first attempts towards a rational ligand design aimed at
      a high selectivity for mono- and diether formation.

PMID- 18720498
TI  - Inducible nature of the enzymes involved in catabolism of caffeine and related
      methylxanthines.
AB  - Previously isolated strain of Pseudomonas sp. has the capability of utilizing
      caffeine as the sole source of carbon and nitrogen and degrading caffeine at
      higher concentrations (>10 g l(-1)). In this study, an assay has been developed
      to study the enzymatic conversion of caffeine to subsequent methylxanthines by
      cell free extracts of Pseudomonas sp., the activity of which has been stabilized
      by use of stabilizers in the lysis buffer. Growth of the strain in various
      methylxanthines and later enzyme assay demonstrated that the enzyme(s) involved
      in degradation of caffeine and other methylxanthines were inducible in nature.
      The results also indicated that more than one enzyme are involved in degradation
      of caffeine to xanthine, which constitute the primary steps in bacterial caffeine
      catabolism.

PMID- 18720499
TI  - Identification and in vitro characterisation of Lactobacillus plantarum strains
      from artisanal Bulgarian white brined cheeses.
AB  - Lactobacillus plantarum strains were isolated from fully ripened, white brined
      Bulgarian home-made cheeses. Strains were derived from phenotypically homogenous
      Lactobacillus group and were identified as L. plantarum based on both phenotypic
      and molecular identification (species-specific and multiplex PCR) methods.
      Heterogeneity of L. plantarum isolates was evaluated by Rep-PCR analysis. Further
      antimicrobial activity, antibiotic susceptibility and transit tolerance of the
      strains were evaluated. Most of them showed broad spectrum of activity against
      Gram-negative bacteria (including human pathogens) independent on the presence of
      organic acids or hydrogen peroxide. All strains were sensitive to amoxicillin and
      sulfamethoxazole/trimethoprim, resistant to clinically relevant beta -lactame
      antibiotics (penicillin and ampicillin) and to nalidixic acid, ciprofloxacin,
      streptomycin, and vancomycin. Significant variability in the sensitivity to
      tetracycline was noted. The tolerance to low pH, bile salts, pepsin and
      pancreatin at concentrations similar to those in the gastrointestinal tract was
      strain-dependent. The exposure to bile salts was less destructive than exposure
      to pH 2.0 for all tested strains. Based on their combined responses to the above
      selection criteria, four L. plantarum strains, RL29, RL34, RL36 and RL37, were
      selected as potential probiotics for in vivo studies.

PMID- 18720500
TI  - Efflux genes and active efflux activity detection in Malaysian clinical isolates
      of methicillin-resistant Staphylococcus aureus (MRSA).
AB  - Efflux-mediated resistance has been recognized as an important contributor of
      antibiotic resistance in bacteria, especially in methicillin-resistant
      Staphylococcus aureus (MRSA) isolates. This study was carried out to detect and
      analyze efflux genes (norA and mdeA) and active efflux activity in a collection
      of Malaysian MRSA and methicillin-sensitive S. aureus (MSSA) clinical isolates.
      Nineteen isolates including three ATCC S. aureus reference strains were subjected
      to PCR detection and DNA sequence analysis for norA and mdeA and active efflux
      detection using modified minimum inhibitory concentration (MIC) assay. From the
      19 isolates, 18 isolates harboured the mdeA gene while 16 isolates contained norA
      gene. DNA sequence analysis reveals 98-100% correlation between the PCR product
      and the published DNA sequences in GenBank. In addition, 16 isolates exhibited
      active efflux activity using the ethidium bromide (EtBr)-reserpine combination
      MIC assay. To our knowledge, this is the first report on the detection of efflux
      genes and active efflux activity amongst Malaysian clinical isolates of
      MRSA/MSSA. Detection of active efflux activity may explain the previous report on
      efflux-mediated drug resistance profile amongst the local clinical isolates.

PMID- 18720501
TI  - Metabolic adaptation and oxaloacetate homeostasis in P. fluorescens exposed to
      aluminum toxicity.
AB  - Microbial systems are known to elaborate intricate metabolic strategies in an
      effort to fend the toxic impact of numerous metals. In this study, we show that
      the exposure of Pseudomonas fluorescens to aluminum (Al) resulted in a metabolic
      shift aimed at diverting oxaloacetate towards the biogenesis of an aluminophore.
      This metabolic alteration was characterized by uncoupling of two gluconeogenic
      enzymes, namely pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase
      (PEPCK). While PC displayed a sharp increase in activity and expression, PEPCK
      was severely diminished. Malic enzyme (ME) and NAD kinase (NADK), two enzymes
      involved in maintaining a reductive environment, were markedly increased in the
      Al-stressed cells. Hence, Al-exposed Pseudomonas fluorescens evoked a metabolic
      response aimed at generating oxaloacetate and promoting an intracellular
      reductive environment.

PMID- 18720502
TI  - Influence of signal-peptide truncations on the functional expression of
      Escherichia coli gamma -glutamyltranspeptidase.
AB  - The full-length Escherichia coli gamma -glutamyltranspeptidase (EcGGT) gene and
      five truncations lacking 33, 51, 54, 60, and 78 bp respectively at the 5' end
      were prepared by polymerase chain reaction and cloned into the expression vector
      pQE-30. Isopropyl-beta -D-thiogalactopyranoside induction of E. coli M15 cells
      bearing the recombinant plasmids resulted in the intracellular production of the
      expressed proteins, EcGGT, EcGGT/DeltaN11, EcGGT/DeltaN17, EcGGT/DeltaN18,
      EcGGT/DeltaN20, and EcGGT/DeltaN26. The overexpressed enzymes were purified to
      near homogeneity by Ni(2+)-NTA resin. The specific activity for EcGGT,
      EcGGT/DeltaN11 and EcGGT/DeltaN17 was 5.3, 4.9, and 4.8 U/mg protein
      respectively, whereas the rest three enzymes had shown no GGT activity under the
      enzyme assay conditions. More than 94% of the activity was found in the
      cytoplasmic fraction of E. coli M15 cells harboring pQE-EcGGT, pQE-EcGGT/DeltaN11
      or pQE-EcGGT/DeltaN17. Western blot analysis confirmed that the majority of N
      terminally truncated enzymes were present in the cytoplasm.

PMID- 18720503
TI  - Ecophysiological requirements and survival of a Trichoderma atroviride isolate
      with biocontrol potential.
AB  - Trichoderma atroviride SC1, isolated from decayed hazelnut wood in northern Italy
      in 2000, is a promising fungal agent for biological control of soil-borne plant
      pathogens. The objective of this research was to characterize the biology and
      ecology of this fungus, in order to determine its environmental parameter
      tolerance levels and its behavior in the phylloplane and soil systems. To better
      characterize T. atroviride SC1, the influences of pH, temperature, water activity
      and different nitrogen and carbon sources on its in vitro growth were evaluated.
      T. atroviride SC1 survival was assessed on strawberry leaves under controlled
      conditions in a greenhouse and in sterilized and non-sterilized soil samples kept
      at room temperature. Results showed that isolate SC1 is mesophilic and grows best
      at 25 degrees C. The fungus tolerates a wide range of pH levels, but growth was
      reduced on alkaline media (pH >or= 8). The nitrogen and carbon sources peptone,
      tryptone, nitrate, mannose, galactose and sucrose were associated with the
      highest mycelial biomass production, as compared with other potential sources of
      nitrogen and carbon. The fungus survived on strawberry leaves under greenhouse
      conditions (25 +/- 2 degrees C, RH = 60 +/- 10%) and grew in sterilized soils at
      room temperature (23 +/- 2 degrees C) for 45 d. However, no increase in mycelial
      dry weight was observed in non-sterilized soils. T. atroviride SC1 survived under
      the test conditions, showing a good potential for use in soil and foliar
      biocontrol applications.

PMID- 18720504
TI  - Establishment of an indicator cell line to quantify bovine foamy virus infection.
AB  - A cell line derived from baby hamster kidney (BHK-21) cells was transfected with
      the enhanced green fluorescent protein gene driven by the bovine foamy virus
      (BFV) long terminal repeat (LTR) to establish a BFV indicator cell line (BICL).
      Among 48 clones, one clone was chosen for its little constitutive enhanced green
      fluorescent protein (EGFP) expression and high level of EGFP expression after
      activation by BFV infection. By detecting the EGFP expression of the BFV
      indicator cell line, the titers of BFV were quantified by the end point method.
      As a result, the titer determined by the EGFP based assay 5-6 days post infection
      (d.p.i.) was 100 fold higher than traditional assays measuring cytopathic effects
      8-9 d.p.i.. Moreover, the EGFP based assay was also used to determine the titer
      of those cells infected by BFV without inducing cytopathic effects. Using this
      simple and rapid assay, we examined the in vitro host range of BFV. It was found
      that BFV can productively infect various cell lines derived from bovine, human,
      rat and monkey.

PMID- 18720505
TI  - More evidence for the association between statins and myasthenia gravis.

PMID- 18720506
TI  - Predominant fiber atrophy and fiber type disproportion in early ullrich disease.
AB  - Ullrich disease (congenital muscular dystrophy type Ullrich, UCMD) is a severe
      congenital disorder of muscle caused by recessive and dominant mutations in the
      three genes that encode the alpha-chains of collagen type VI. Little is known
      about the early pathogenesis of this myopathy. The aim of this study was to
      investigate early histological changes in muscle of patients with molecularly
      confirmed UCMD. Muscle biopsies were analyzed from 8 UCMD patients ranging in age
      from 6 to 30 months. Type I fiber atrophy and predominance were seen early,
      together with a widening of the fiber diameter spectrum, whereas no dystrophic
      features were apparent. A subpopulation of more severely atrophic type I fibers
      was apparent subsequently, including one biopsy that fulfilled the formal
      diagnostic criteria of histopathological fiber type disproportion (FTD). Thus,
      early in the disease, UCMD presents as a non-dystrophic myopathy with predominant
      fiber atrophy. Collagen VI mutations also qualify as a cause of fiber type
      disproportion.

PMID- 18720509
TI  - MnSOD deficiency has a differential effect on disease progression in two
      different ALS mutant mouse models.
AB  - Mitochondrial dysfunction and oxidative stress are thought to participate in the
      pathogenesis of amyotrophic lateral sclerosis (ALS). The purpose of this study
      was to determine the effect of reduced mitochondrial antioxidant defense on
      lifespan and disease progression in two mouse models of familial ALS (G93A and
      H46R/H48Q mutant lines) that represent pseudo-wildtype and metal-deficient ALS
      mutants, respectively. The metal-deficient H46R/H48Q mutant differs from the G93A
      mutant in that it cannot bind copper in the active site and thus lacks SOD
      activity. We crossed each of these mutant lines with mice deficient in the
      mitochondrial matrix antioxidant enzyme MnSOD (Sod2+/- mice). In both high
      (G93A1Gur) and low (G93ADL) copy G93A strains, MnSOD deficiency caused a decrease
      in lifespan that was associated with a reduced disease duration rather than
      earlier disease onset. In contrast, MnSOD deficiency had no effect on lifespan or
      disease parameters of H46R/H48Q mutant mice. MnSOD deficiency thus has a
      differential effect on disease progression in different mutant SOD1 ALS mouse
      models, suggesting that different ALS-causing mutations in SOD1 result in disease
      progression by at least proximally different mechanisms/pathways.

PMID- 18720508
TI  - Statins may aggravate myasthenia gravis.
AB  - Statin-induced myopathy is well-known, but the effect of cholesterol-lowering
      agents on myasthenia gravis (MG) has not been studied in detail. We investigated
      statin use and its effects on MG among patients with this disease. Statin
      information was systemically obtained from 170 patients being treated at the
      Neuromuscular Disease Clinic at the University of Alabama at Birmingham. When a
      new myalgic syndrome or worsening of MG developed within 4 months after statin
      treatment, no other likely cause was found, and clinical improvement occurred
      either with or without discontinuation of the statin, we considered these
      symptoms to be statin-induced. Fifty-four patients (31%) were on statins. The
      statin group had proportionally more males, and older patients compared with the
      non-statin group. A myalgic syndrome was noted in 7 (13%) patients, but it
      resolved without any sequelae after withdrawal of the statin. MG worsening
      occurred in 6 (11%) patients without regard to type of MG or brand of statin. MG
      worsening occurred independently of myalgic syndrome and involved predominantly
      oculobulbar symptoms within 1-16 weeks of statin treatment. In 4 patients,
      additional treatment was needed to reverse MG worsening. Statins are safe in the
      majority of MG patients, but their use must be accompanied by close observation
      for possible MG worsening.

PMID- 18720511
TI  - Severe hydroxychloroquine myopathy.
AB  - Hydroxychloroquine causes a vacuolar myopathy that is usually of mild to moderate
      severity. The myopathy may be underrecognized, especially in patients who receive
      multiple other medications for complex illnesses. We report two patients with
      connective tissue diseases and unusually severe, histopathologically proven
      hydroxychloroquine myopathy. Both had ventilatory failure; one also had primary
      pulmonary disease associated with scleroderma, but the other lacked a pulmonary
      etiology. The ventilatory failure and subsequent medical complications led to
      death despite discontinuation of hydroxychloroquine, thereby underscoring the
      potential severity of hydroxychloroquine myopathy and the need for its early
      recognition.

PMID- 18720514
TI  - Glutamate receptor subunits expression in memory-associated brain structures:
      regional variations and effects of aging.
AB  - We investigated regional variations and the effects of aging on the expression of
      the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      (AMPA) receptor subunits in several memory-associated structures using Western
      blotting. In young adult rats, NR1, NR2A, and GluR2 levels varied between the
      hippocampus and parahippocampal region and between the subregions of the
      hippocampus. When a comparison was made between young (4-month-old) and aged (24
      month-old) rats, significant decreases in NR1 expression were found in the aged
      ventral hippocampus and the entorhinal and postrhinal cortices. There were
      significant decreases in NR2A expression in the aged parahippocampal region, but
      not in the hippocampus. The expression of the GluR2 subunit was significantly
      reduced in the ventral hippocampus and the postrhinal cortex. A dramatic decrease
      in NR1 and GluR2 expression was found in the aged CA2/3 and CA1, respectively,
      but there were no significant age-related changes in NR2A expression. All three
      subunits were expressed at a similar level in the two age groups in the
      prefrontal cortex. These results suggest differential expression and effects of
      aging on NMDA and AMPA receptor subunits in memory-associated brain structures.

PMID- 18720513
TI  - HIV entry inhibitors and their potential in HIV therapy.
AB  - This review discusses recent progress in the development of anti-HIV agents
      targeting the viral entry process. The three main classes (attachment inhibitors,
      co-receptor binding inhibitors, and fusion inhibitors) are further broken down by
      specific mechanism of action and structure. Many of these inhibitors are in
      advanced clinical trials, including the HIV maturation inhibitor bevirimat, from
      the authors' laboratories. In addition, the CCR5 inhibitor maraviroc has recently
      been FDA-approved. Possible roles for these agents in anti-HIV therapy, including
      treatment of virus resistant to current drugs, are also discussed.

PMID- 18720516
TI  - Cocaine abuse and sensitization of striatal dopamine transmission: a critical
      review of the preclinical and clinical imaging literature.
AB  - Much effort has been devoted in the preclinical addiction literature to
      understanding the phenomenon of sensitization, an enhanced dopaminergic response
      in the nucleus accumbens that occurs after repeated exposure to psychostimulant
      drugs. Although sensitization has been reported in preclinical studies, studies
      of sensitization in humans measuring behavioral and physiological responses have
      been mixed and inconclusive. However, imaging studies with positron emission
      tomography (PET) and single photon emission computed tomography (SPECT) using a
      stimulant challenge to induce dopamine (DA) release provide a unique opportunity
      to probe DA transmission in cocaine dependent human subjects. In contrast to the
      basic science literature that predicted sensitization, three independent cohorts
      have shown a blunted DA response, or the opposite of sensitization, in human
      cocaine dependent subjects. This article reviews the methodological differences
      between the preclinical and clinical PET studies that have investigated DA
      sensitization in order to address the discrepancy between the human and animal
      literature.

PMID- 18720515
TI  - Altered hippocampal expression of glutamate receptors and transporters in GRM2
      and GRM3 knockout mice.
AB  - Group II metabotropic glutamate receptors (mGluR2 and mGluR3, also called mGlu2
      and mGlu3, encoded by GRM2 and GRM3, respectively) are therapeutic targets for
      several psychiatric disorders. GRM3 may also be a schizophrenia susceptibility
      gene. mGluR2-/- and mGluR3-/- mice provide the only unequivocal means to
      differentiate between these receptors, yet interpretation of in vivo findings may
      be complicated by secondary effects on expression of other genes. To address this
      issue, we examined the expression of NMDA receptor subunits (NR1, NR2A, NR2B) and
      glutamate transporters (EAAT1-3), as well as the remaining group II mGluR, in the
      hippocampus of mGluR2-/- and mGluR3-/- mice, compared with wild-type controls.
      mGluR2 mRNA was increased in mGluR3-/- mice, and vice versa. NR2A mRNA was
      increased in both knockout mice. EAAT1 (GLAST) mRNA and protein, and EAAT2 (GLT
      1) protein, were reduced in mGluR3-/- mice, whereas EAAT3 (EAAC1) mRNA was
      decreased in mGluR2-/- mice. Transcripts for NR1 and NR2B were unchanged. The
      findings show a compensatory upregulation of the remaining group II metabotropic
      glutamate receptor in the knockout mice. Upregulation of NR2A expression suggests
      modified NMDA receptor signaling in mGluR2-/- and mGluR3-/- mice, and
      downregulation of glutamate transporter expression suggests a response to altered
      synaptic glutamate levels. The results show a mutual interplay between mGluR2 and
      mGluR3, and also provide a context in which to interpret behavioral and
      electrophysiological results in these mice.

PMID- 18720517
TI  - Dopamine modulating drugs influence striatal (+)-[11C]DTBZ binding in rats: VMAT2
      binding is sensitive to changes in vesicular dopamine concentration.
AB  - Binding of (+)-[11C]DTBZ (dihydrotetrabenazine) to the striatal vesicular
      monoamine transporter (VMAT2) is widely considered to be a stable marker of
      dopamine neurone integrity. However, we now find that specific binding of a
      tracer dose of (+)-[11C]DTBZ is modestly increased in rat striatum following
      dopamine depletion with alpha-methyl-p-tyrosine (alpha-MPT, +14%) or d
      amphetamine (d-AMPH, 20 mg/kg, +12%) and decreased following dopamine elevation
      with gamma-hydroxybutyrate (GHB, -16%) or levodopa (-20%). We suggest that in
      vivo (+)-[11C]DTBZ binding in imaging studies is subject to competition by
      vesicular dopamine and, in this respect, is not a "stable" dopamine biomarker as
      is generally assumed.

PMID- 18720518
TI  - Nomogram for deciding adjuvant treatment after surgery for oral cavity squamous
      cell carcinoma.
AB  - BACKGROUND: The application of appropriate adjuvant treatment after surgery for
      oral cavity squamous cell carcinoma (OCSCC) is predicated on accurate patient
      risk stratification. METHODS: A nomogram for estimating locoregional recurrence
      free survival (LRFS) after treatment of OCSCC was constructed from a cohort of
      590 patients with OCSCC who were treated at Memorial Sloan-Kettering Cancer
      Center (MSKCC). The nomogram was validated using a series of 417 patients with
      OCSCC who were treated at Hospital do Cancer AC Camargo (HACC) in Sao Paulo,
      Brazil. RESULTS: Despite significant differences between the MSKCC and HACC
      cohorts, the nomogram was able to predict LRFS from OCSCC with a concordance
      index of 0.693. Further statistical analysis showed that the nomogram was well
      calibrated. CONCLUSIONS: This preliminary nomogram is the first prognostic model
      developed and externally validated to predict the likelihood of LRFS after
      treatment for an individual patient with OCSCC and may have practical utility for
      deciding adjuvant treatment.

PMID- 18720519
TI  - Pharyngeal swallowing dysfunction following treatment for oral and pharyngeal
      cancer--association with diminished intraoral sensation and discrimination
      ability.
AB  - BACKGROUND: Swallowing disorders following treatment for oral and pharyngeal
      cancer are mainly considered a surgical sequel. The recent finding that
      radiotherapy-induced decline in intraoral sensory abilities established an
      incentive to elucidate any association between the degree of sensory decline and
      the degree of swallowing dysfunction. METHODS: Oral and pharyngeal swallowing was
      cineradiographically examined in 15 patients with oral or pharyngeal cancer
      before and after treatment. The patients were also tested for intraoral
      sensation, shape recognition, and hole size identification. RESULTS: Swallowing
      function deteriorated in 67% of the patients 6 months posttreatment, with no
      significant improvement after 12 months. The degree of swallowing dysfunction was
      statistically significantly associated with the degree of diminished intraoral
      sensation and shape recognition. CONCLUSION: In the quest for rehabilitation
      after treatment for oral and pharyngeal cancer, the impact of impaired intraoral
      sensation and discrimination ability on swallowing function should be taken into
      consideration.

PMID- 18720520
TI  - Speech outcomes after soft palate reconstruction with the soft palate
      insufficiency repair procedure.
AB  - BACKGROUND: Measurement of functional outcomes related to different methods of
      soft palate reconstruction is necessary to determine efficacy of surgical
      intervention after resection for oropharyngeal cancer. METHODS: Speech data were
      collected across 4 evaluation times for 4 groups of patients (2 groups consisted
      of patients with <or= half the soft palate resected followed by conventional
      reconstruction; 2 groups consisted of patients with half or more of the soft
      palate resected followed by reconstruction with an adhesion or the soft palate
      insufficiency repair (SPIR). RESULTS: Sixty-two patients were included. Speech
      was preserved when conventional reconstructive procedures were used to close
      smaller defects. For larger defects, reconstruction with an adhesion resulted in
      poorer speech outcomes than the SPIR. The SPIR group achieved normal speech
      results at all points of evaluation. CONCLUSIONS: The results demonstrate that
      the SPIR is emerging as an efficacious surgical technique for reconstruction of
      larger soft palate defects.

PMID- 18720521
TI  - Atelectasis after free rectus transfer and abdominal wall reconstruction.
AB  - BACKGROUND: Atelectasis is commonly encountered in patients undergoing rectus
      abdominus tissue transfer. Primary closure of the anterior rectus sheath may
      contribute to this process. Augmentation of the closure with mesh may decrease
      the incidence of Atelectasis. METHODS: In this retrospective review 32 patients
      with preoperative and postoperative augmentation were compared to 23 who had
      primary closure of the anterior rectus sheath. RESULTS: Augmentation consisted of
      acellular dermis (25) or mesh (7). Postoperative atelectasis was radiographically
      detected in: 91% (n=29) of augmented patients versus 83% (n=19) of primary
      closure patients. Major atelectasis in 41% (n=13) of augmented patients versus
      61% (n=14) of primary closure patients p<.05. The incidence of atelectasis was
      independent of skin flap size and operative times. CONCLUSIONS: The use of
      acellular dermis or mesh to augment the abdominal wall appears to reduce the high
      incidence of postoperative atelectasis following rectus-free flap harvest.

PMID- 18720522
TI  - Telomere-mediated genomic instability and the clinico-pathological parameters in
      breast cancer.
AB  - A study was undertaken to correlate telomere dysfunction and genomic instability
      with the histopathological grades and the estrogen and progesterone receptor
      status in breast cancer. Sixty-one archived breast tissues (38 cancer tissues and
      23 paired normal tissues) were used in the study. The breast tumor tissues showed
      significantly shorter telomeres (7.7 kb) compared with the paired adjacent
      tissues (9.0 kb) by Southern blot analysis. Moreover, telomere shortening was
      more significant in Grade III tumors than in the Grade II tumors (P = 0.05).
      Quantitative fluorescence in situ hybridization on paraffin tissue sections
      revealed a similar trend in telomere shortening. Telomere attrition was
      associated with telomere dysfunction as revealed by the presence of significantly
      higher anaphase bridges in tumor cells which was tumor grade dependent.
      Furthermore, estrogen receptive negative tumors displayed higher anaphase and
      internuclear bridges. Selected samples from each grade showed greater genomic
      imbalances in the higher grades than the lower grade tumors as detected by array
      comparative genomic hybridization. Telomerase activity was found to be higher in
      the higher grades (Grade II and III) compared with the lower grade (Grade I). The
      average mRNA expression of TRF1 and POT1 was lower in the tumor tissues than in
      the normal tissues. Tankyrase 1 mRNA expression showed a grade-dependent increase
      in tumor tissues and its expression was also high in estrogen and progesterone
      negative tumors. The data support the notion that telomere dysfunction might be
      of value as a marker of aggressiveness of the tumors in breast cancer patients.

PMID- 18720523
TI  - Prognostic significance of secondary cytogenetic alterations in follicular
      lymphomas.
AB  - Follicular lymphoma (FL) is an indolent lymphoma with a long median survival.
      Transformation to a more aggressive histology (TLy) is a major cause of
      mortality. The critical events leading to TLy are unknown. We assessed the
      prognostic significance of secondary cytogenetic alterations on overall survival
      (OS) and transformation from 210 diagnostic FL biopsies. We analyzed serial and
      transformed karyotypes for recurrent alterations that predict transformation.
      Over 10 years, 31% of cases developed TLy. The only alteration in diagnostic
      karyotypes that correlated with an inferior OS was an additional X chromosome in
      males only (P = 0.005) suggesting that other mechanisms including epigenetic
      factors and over-expression of genes on the X chromosome may play a role in FL
      pathogenesis. In transformed karyotypes, 8q24 (MYC) translocations were common
      (14/37) and resulted in a median survival of 3 months posttransformation (P =
      0.01). In serially obtained biopsies (28 pts), 43% of the later biopsies lacked
      the cytogenetic alterations found in the original FL karyotype, suggesting that
      karyotypic progression of FL is not strictly linear in all cases. Consequently,
      studying clonal evolution in FL using serial biopsies may not represent the full
      complexity of genetic alterations leading to transformation.

PMID- 18720525
TI  - Evaluation of sonographic diagnostic criteria for placenta accreta.
AB  - PURPOSE: To compare the diagnostic value of reported sonographic criteria for
      placenta accreta and to develop a composite score system for antenatal
      evaluation. METHOD: Sixty-six women at risk for placenta accreta were examined
      for 9 cases of placenta accreta that were confirmed at delivery. The performance
      of previously reported gray-scale and Doppler sonographic criteria for the
      diagnosis of placenta accreta was analyzed individually. A composite score system
      was developed by combining selected sensitive or specific sonographic criteria,
      and its performance was evaluated. RESULTS: The criteria of obliteration of
      retroplacental clear space, a myometrial thickness of <1 mm, presence of vessels
      bridging placenta and uterine margin, disruption of the placental-uterine wall
      interface, and vessels crossing the sites of interface disruption showed a
      statistically significant association with placenta accreta. The disruption of
      the placental-uterine wall interface and the presence of vessels crossing these
      sites were the only 2 individual criteria that could distinguish placenta accreta
      from non-accreta, which could also be achieved by our composite score system
      using a cutoff value of 40, with a sensitivity of 89% and specificity of 98%.
      CONCLUSION: The diagnostic performance of the sonographic diagnostic criteria
      used in the diagnosis of placenta accreta varies, and a composite score system
      improves the overall accuracy.

PMID- 18720524
TI  - Differential patterns of allelic loss in estrogen receptor-positive infiltrating
      lobular and ductal breast cancer.
AB  - The two main histological types of infiltrating breast cancer, lobular (ILC) and
      the more common ductal (IDC) carcinoma are morphologically and clinically
      distinct. To assess the molecular alterations associated with these breast cancer
      subtypes, we conducted a whole-genome study of 166 archival estrogen receptor
      (ER)-positive tumors (89 IDC and 77 ILC) using the Affymetrix GeneChip(R) Mapping
      10K Array to identify sites of loss of heterozygosity (LOH) that either
      distinguished, or were shared by, the two phenotypes. We found single nucleotide
      polymorphisms (SNPs) of high-frequency LOH (>50%) common to both ILC and IDC
      tumors predominately in 11q, 16q, and 17p. Overall, IDC had a slightly higher
      frequency of LOH events across the genome than ILC (fractional allelic loss =
      0.186 and 0.156). By comparing the average frequency of LOH by chromosomal arm,
      we found IDC tumors with significantly (P < 0.05) higher frequency of LOH on 3p,
      5q, 8p, 9p, 20p, and 20q than ILC tumors. We identified additional chromosomal
      arms differentiating the subtypes when tumors were stratified by tumor size,
      mitotic rate, or DNA content. Of 5,754 informative SNPs (>25% informativity), we
      identified 78 and 466 individual SNPs with a higher frequency of LOH (P < 0.05)
      in ILC and IDC tumors, respectively. Hierarchical clustering of these 544 SNPs
      grouped tumors into four major groups based on their patterns of LOH and
      retention of heterozygosity. LOH in chromosomal arms 8p and 5q was common in
      higher grade IDC tumors, whereas ILC and low-grade IDC grouped together by virtue
      of LOH in 16q.

PMID- 18720527
TI  - Zoledronic acid and skeletal complications in patients with solid tumors and bone
      metastases: analysis of a national medical claims database.
AB  - BACKGROUND: Bone is among the most common sites of metastasis in patients with
      advanced cancer, and the development of bone metastases places patients at
      increased risk for skeletal complications. METHODS: This retrospective claims
      analysis included only patients with a diagnosis of bone metastasis who had a
      single type of solid tumor of the breast (women), prostate, or lung and
      experienced >or=1 skeletal complication between January 2002 and October 2005.
      RESULTS: The mean follow-up (+/-standard deviation) for zoledronic acid (ZA)
      treated patients versus untreated patients was 12.2 +/- 9.05 months versus 8.7 +/
      9.28 months, respectively (P < .001). The monthly rate of skeletal complications
      in ZA-treated patients versus untreated patients was 0.29 +/- 0.3 per month
      versus 0.43 +/- 0.4 per month, respectively (P < .001). Persistent ZA use was
      associated with longer follow-up duration (P < .05) and a greater probability of
      continuing follow-up. Greater persistency was associated with lower monthly rates
      of skeletal complications (P < .05). The length of follow-up for ZA use according
      to the recommended dosing schedule was 17.11 months compared with 9.93 months for
      nonrecommended schedules and 8.68 months for no treatment (analysis of variance;
      P < .001). The rate of skeletal complications with ZA use on the recommended
      schedule was 0.16 events per month versus 0.31 events per month for
      nonrecommended schedules and 0.43 events per month for no treatment. In the
      subgroup analysis, the mean time to first complication was 185 +/- 210 days in
      the ZA-treated group versus 98 +/- 161 days in the untreated group (P < .0001).
      The mean time from the first complication to the second complication was 111 +/-
      124 days in the ZA-treated group versus 86 +/- 114 days in the untreated group (P
      < .05). CONCLUSIONS: Real-world evidence indicated that ZA reduced the skeletal
      morbidity rate and delayed the time to skeletal complications.

PMID- 18720528
TI  - Selective colorimetric sensing of geometrical isomers of dicarboxylates in water
      by using functionalized gold nanoparticles.
AB  - A colorimetric sensing system based on gold nanoparticles functionalized with a
      water-soluble anion-recognition motif, an o-(carboxamido)trifluoroacetophenone
      analogue, has been developed. The nanoparticle system selectively senses specific
      isomers of dicarboxylates that are geometrically favorable for the binding
      induced aggregation process; thus, it discriminates a trans-dicarboxylate
      fumarate from its cis-isomer maleate, and benzene-1,4-dicarboxylate from its
      isomeric benzene-1,2-and benzene-1,3-dicarboxylates in water, exhibiting a color
      change from red to blue.

PMID- 18720529
TI  - A parylene-based dual channel micro-electrophoresis system for rapid mutation
      detection via heteroduplex analysis.
AB  - A new dual channel micro-electrophoresis system for rapid mutation detection
      based on heteroduplex analysis was designed and implemented. Mutation detection
      was successfully achieved in a total separation length of 250 microm in less than
      3 min for a 590 bp DNA sample harboring a 3 bp mutation causing an amino acid
      change. Parylene-C was used as the structural material for fabricating the micro
      channels as it provides conformal deposition, transparency, biocompatibility, and
      low background fluorescence without any surface treatment. A new dual channel
      architecture was derived from the traditional cross-channel layout by forming two
      identical channels with independent sample loading and waste reservoirs. The
      control of injected sample volume was accomplished by a new u-turn injection
      technique with pull-back method. The use of heteroduplex analysis as a mutation
      detection method on a cross-linked polyacrylamide medium provided accurate
      mutation detection in an extremely short length and time. The presence of two
      channels on the microchip offers the opportunity of comparing the sample to be
      tested with a desired control sample rapidly, which is very critical for the
      accuracy and reliability of the mutation analyses, especially for clinical and
      research purposes.

PMID- 18720530
TI  - Chemokine receptor CXCR4-prognostic factor for gastrointestinal tumors.
AB  - To review the implication of CXCR4 for gastrointestinal cancer, a "Pubmed"
      analysis was performed in order to evaluate the relevance of CXCR4 and its
      ligands for gastrointestinal cancers. Search terms applied were "cancer,
      malignoma, esophageal, gastric, colon, colorectal, hepatic, pancreatic, CXCR4,
      SDF-1alpha, and SDF-1beta". CXCR4 expression correlated with dissemination of
      diverse gastrointestinal malignomas. The CXCR4 ligand SDF-1alpha might act as
      "chemorepellent" while SDF-1beta might act as "chemorepellent" for CTLs, inducing
      tumor rejection. The paracrine expression of SDF-1alpha was furthermore closely
      associated with neoangiogenesis. CXCR4 and its ligands influence the
      dissemination, immune rejection, and neoangiogenesis of human gastrointestinal
      cancers. Inhibition of CXCR4 might be an interesting therapeutic option.

PMID- 18720531
TI  - Hepatitis G virus.
AB  - A number of new hepatitis viruses (G, TT, SEN) were discovered late in the past
      century. We review the data available in the literature and our own findings
      suggesting that the new hepatitis G virus (HGV), disclosed in the late 1990s, has
      been rather well studied. Analysis of many studies dealing with HGV mainly
      suggests the lymphotropicity of this virus. HGV or GBV-C has been ascertained to
      influence course and prognosis in the HIV-infected patient. Until now, the
      frequent presence of GBV-C in coinfections, hematological diseases, and biliary
      pathology gives no grounds to determine it as an "accidental tourist" that is of
      no significance. The similarity in properties of GBV-C and hepatitis C virus
      (HCV) offers the possibility of using HGV, and its induced experimental
      infection, as a model to study hepatitis C and to develop a hepatitis C vaccine.

PMID- 18720532
TI  - Therapy for acute pancreatitis with platelet-activating factor receptor
      antagonists.
AB  - Acute pancreatitis (AP) causes release of platelet-activating factor (PAF), which
      induces systemic effects that contribute to circulatory disturbances and multiple
      organ failure. PAF is a cell surface secretion of bioactive lipid, which could
      produce physiological and pathological effects by binding to its cell surface
      receptor called platelet-activating factor receptor (PAF-R). Studies showed that
      PAF participate in the occurrence and development of AP and administration of
      platelet-activating factor receptor antagonists (PAF-RAs) could significantly
      reduce local and systemic events after AP. PAF has also been implicated as a key
      mediator in the progression of severe AP, which can lead to complications and
      unacceptably high mortality rates. Several classes of compounds show significant
      PAF-RAs, and significant local and systemic effects on reducing inflammatory
      changes. As a preventive treatment, PAF-RA could block a series of PAF-mediated
      inflammatory injury and thus improve the prognosis of AP. This review introduces
      the important role of PAF-RA in the treatment of AP.

PMID- 18720533
TI  - Nuclear factor kappa B: a marker of chemotherapy for human stage IV gastric
      carcinoma.
AB  - AIM: To detect the nuclear factor kappa B (NF-kappaB) condition in human stage IV
      gastric carcinoma patients and to explore the correlation between NF-kappaB
      activation and survival of these patients after chemotherapy. METHODS: Expression
      of NF-kappaB-p65 was determined by immunohistochemical analysis. Activity of NF
      kappaB DNA-binding in carcinoma tissue was detected by electrophoretic mobility
      shift assay. Kaplan-Meier survival analysis was performed to show the relation
      between NF-kappaB and progression-free survival (PFS) or overall survival (OS) of
      the patients. RESULTS: The positive expression rate of NF-kappaB-p65 in 60
      gastric cancer tissue samples was 76.7% (46/60). The expression of NF-kappaB-p65
      was reduced in adjacent carcinoma and normal tissue samples. Electrophoretic
      mobility shift assay (EMSA) analysis showed a strong activation of NF-kappaB in
      cancer tissue samples. A survival difference was found in NF-kappaB-p65 positive
      and negative patients. NF-kappaB-p65 expression was negative in cancer tissue
      samples (n=14). PFS was 191.40+/-59.88 d and 152.93+/-16.99 d, respectively, in
      patients with positive NF-kappaB-p65 expression (n=46) (P=0.4028). The survival
      time of patients with negative and positive NF-kappaB-p65 expression was 425.16+/
      61.61 d and 418.85+/-42.98 d, respectively (P=0.7303). Kaplan-Meier analysis
      showed no significant difference in PFS or OS. The 46 patient tissue which
      positive NF-kappaB-p65 expression was found in the tissue samples from the 46
      patients whose PFS and OS were 564.89+/-75.94 d and s 352.37+/-41.32 d,
      respectively (P=0.0165). CONCLUSION: NF-kappaB is activated in gastric carcinoma
      tissue, which is related to the OS after chemotherapy.

PMID- 18720534
TI  - Revaluation of clinical and histological criteria for diagnosis of dysmetabolic
      iron overload syndrome.
AB  - AIM: To re-evaluate the diagnostic criteria of insulin resistance hepatic iron
      overload based on clinical, biochemical and histopathological findings. METHODS:
      We studied 81 patients with hepatic iron overload not explained by known genetic
      and acquired causes. The metabolic syndrome (MS) was defined according to ATPIII
      criteria. Iron overload was assessed by liver biopsy. Liver histology was
      evaluated by Ishak's score and iron accumulation by Deugnier's score; steatosis
      was diagnosed when present in >or=5% of hepatocytes. RESULTS: According to
      transferrin saturation levels, we observed significant differences in the amount
      of hepatic iron overload and iron distribution, as well as the number of
      metabolic abnormalities. Using Receiving Operating Curve analysis, we found that
      the presence of two components of the MS differentiated two groups with a
      statistically significant different hepatic iron overload (P<0.0001). Patients
      with >or=2 metabolic alterations and steatosis had lower amount of hepatic iron,
      lower transferrin saturation and higher sinusoidal iron than patients with <2 MS
      components and absence of steatosis. CONCLUSION: In our patients, the presence of
      >or2 alterations of the MS and hepatic steatosis was associated with a moderate
      form of iron overload with a prevalent sinusoidal distribution and a normal
      transferrin saturation, suggesting the existence of a peculiar pathogenetic
      mechanism of iron accumulation. These patients may have the typical dysmetabolic
      iron overload syndrome. By contrast, patients with transferrin saturation>or=60%
      had more severe iron overload, few or no metabolic abnormalities and a
      hemochromatosis-like pattern of iron overload.

PMID- 18720535
TI  - Prevention of hepatotoxicity due to anti tuberculosis treatment: a novel
      integrative approach.
AB  - AIM: To evaluate the ability of Curcuma longa (CL) and Tinospora cordifolia (TC)
      formulation to prevent anti-tuberculosis (TB) treatment (ATT) induced
      hepatotoxicity. METHODS: Patients with active TB diagnosis were randomized to a
      drug control group and a trial group on drugs plus an herbal formulation.
      Isoniazid, rifampicin, pyrazinamide and ethambutol for first 2 mo followed by
      continuation phase therapy excluding Pyrazinamide for 4 mo comprised the anti
      tuberculous treatment. Curcumin enriched (25%) CL and a hydro-ethanolic extract
      enriched (50%) TC 1 g each divided in two doses comprised the herbal adjuvant.
      Hemogram, bilirubin and liver enzymes were tested initially and monthly till the
      end of study to evaluate the result. RESULTS: Incidence and severity of
      hepatotoxicity was significantly lower in trial group (incidence: 27/192 vs
      2/316, P<0.0001). Mean aspartate transaminase (AST) (195.93+/-108.74 vs 85+/
      4.24, P<0.0001), alanine transaminase (ALT) (75.74+/-26.54 vs 41+/-1.41,
      P<0.0001) and serum bilirubin (5.4+/-3.38 vs 1.5+/-0.42, P<0.0001). A lesser
      sputum positivity ratio at the end of 4 wk (10/67 vs 4/137, P=0.0068) and
      decreased incidence of poorly resolved parenchymal lesion at the end of the
      treatment (9/152 vs 2/278, P=0.0037) was observed. Improved patient compliance
      was indicated by nil drop-out in trial vs 10/192 in control group (P<0.0001).
      CONCLUSION: The herbal formulation prevented hepatotoxicity significantly and
      improved the disease outcome as well as patient compliance without any toxicity
      or side effects.

PMID- 18720536
TI  - Ultrastructural view of colon anastomosis under propolis effect by transmission
      electron microscopy.
AB  - AIM: To evaluate the effect of propolis administration on the healing of colon
      anastomosis with light and transmission electron microscopes. METHODS: Forty
      eight Wistar-Albino female rats were divided into two groups and had colon
      resection and anastomosis. In group I, rats were fed with standard rat chow pre-
      and postoperatively. The rats in group II were fed with standard rat chow and
      began receiving oral supplementation of propolis 100 mg/kg per day beginning 7 d
      before the operation and continued until they were sacrificed. Rats were
      sacrificed 1, 3, 7 and 14 d after operation, and anastomotic bursting pressures
      measured. After the resection of anastomotic segments, histopathological
      examination was performed with light and transmission electron microscopes by two
      blinded histologists and photographed. RESULTS: The colonic bursting pressures of
      the propolis group were statistically significantly better than the control
      group. Ultrastructural histopathological analysis of the colon anastomosis
      revealed that propolis accelerated the phases of the healing process and
      stimulated mature granulation tissue formation and collagen synthesis of
      fibroblasts. CONCLUSION: Bursting pressure measurements and ultra structural
      histopathological evaluation showed that administration of propolis accelerated
      the healing of colon anastomosis following surgical excision.

PMID- 18720537
TI  - Prevalence of metabolic syndrome, obesity and diabetes type 2 in cryptogenic
      cirrhosis.
AB  - AIM: To evaluate the prevalence of metabolic syndrome (MS), obesity and type 2
      diabetes mellitus (T2DM) in a group of Mexican Mestizo patients with cryptogenic
      cirrhosis (CC) and to compare this group with patients with cirrhosis secondary
      to other causes (disease controls). METHODS: Patients with CC, diagnosed between
      January, 1990 and April, 2005, were included in a retrospective study. Patients
      with cirrhosis caused by chronic hepatitis C, alcohol abuse or autoimmune
      hepatitis (AIH) served as disease controls. RESULTS: A total of 134 patients with
      CC were analyzed. Disease controls consisted of 81 patients with chronic
      hepatitis C, 33 with alcohol abuse and 20 with AIH. The median age of patients
      with CC was 57 years (range, 16-87); 83 (61.9%) patients were female; 53 (39.6%)
      were Child A, 65 (48.5%) Child B, and 16 (11.9%) were Child C cirrhosis. The
      prevalence of MS (29.1% vs 6%; P<0.001), obesity (16.4% vs 8.2%; P=0.04) and T2DM
      (40% vs 22.4%; P=0.013) was higher in CC patients than in disease controls. There
      were no differences in sex, age or liver function tests between the two groups.
      CONCLUSION: The prevalence of MS, obesity and T2DM were higher in patients with
      CC than in patients with cirrhosis secondary to others causes. Our findings
      support the hypothesis that non-alcoholic steatohepatitis (NASH) plays an under
      recognized role in CC.

PMID- 18720538
TI  - Modification of end-loop ileostomy for the treatment of ischemic or radiation
      enteritis.
AB  - AIM: To evaluate a new technique of temporary ileal anastomotic stoma, following
      small bowel resection, in patients where the anastomosis is anticipated to have
      borderline margins with dubious viability. METHODS: Five patients underwent
      enterectomy and partially anastomosed end-loop ileostomy at the University
      Hospital of Larissa between 2000 and 2006. Enterectomy was performed because of
      conditions such as mesenteric vascular occlusive disease, radiation entritis and
      small bowel injury. RESULTS: Postoperatively, none of the patients developed any
      stoma-related or anastomotic complications. There were no major complications.
      All patients were discharged between the 8th and 15th day after the procedure,
      and the stoma was closed 3 wk to 4 wk later. CONCLUSION: We believe that our
      proposed modification of end-loop ileostomy is a simple, quick and safe technique
      with minimal stoma-related morbidity, and with simple and safe reversion. This
      technique can be considered as a useful option in the treatment of ischemic or
      radiation-induced enteritis, and in the management of severe intestinal trauma.

PMID- 18720539
TI  - Thalidomide effect in endothelial cell of acute radiation proctitis.
AB  - AIM: To determine whether thalidomide prevents microvascular injury in acute
      radiation proctitis in white rats. METHODS: Fourteen female Wistar rats were
      used: six in the radiation group, six in the thalidomide group, and two in normal
      controls. The radiation and thalidomide groups were irradiated at the pelvic area
      using a single 30 Gy exposure. The thalidomide (150 mg/kg) was injected into the
      peritoneum for 7 d from the day of irradiation. All animals were sacrificed and
      the rectums were removed on day 8 after irradiation. The microvessels of resected
      specimens were immunohistochemically stained with thrombomodulin (TM), von
      Willebrand Factor (vWF), and vascular endothelial growth factor (VEGF). RESULTS:
      The microscopic scores did not differ significantly between the radiation and
      thalidomide groups, but both were higher than in the control group. Expression of
      TM was significantly lower in the endothelial cells (EC) of the radiation group
      than in the control and thalidomide groups (P<0.001). The number of capillaries
      expressing vWF in the EC was higher in the radiation group (15.3+/-6.8) than in
      the control group (3.7+/-1.7), and the number of capillaries expressing vWF was
      attenuated by thalidomide (10.8+/-3.5, P<0.001). The intensity of VEGF expression
      in capillaries was greater in the radiation group than in the control group and
      was also attenuated by thalidomide (P=0.003). CONCLUSION: The mechanisms of acute
      radiation-induced proctitis in the rats are related to endothelial cell injury of
      microvessel, which may be attenuated with thalidomide.

PMID- 18720540
TI  - Irsogladine maleate suppresses indomethacin-induced elevation of proinflammatory
      cytokines and gastric injury in rats.
AB  - AIM: To investigate the mucosal protective effect and the mechanisms of action of
      the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin
      in rats. METHODS: Gastric mucosal injury was induced in male Hos:Donryu rats by
      oral administration of indomethacin at a dose of 48 mg/kg. One hour before
      indomethacin treatment, animals were orally pretreated with irsogladine maleate
      at doses of 1 mg/kg, 3 mg/kg or 10 mg/kg. Four hours after indomethacin
      administration, the animals were sacrificed and their stomachs were rapidly
      removed and processed for the evaluation of gastric mucosal damage and the
      determination of the concentrations of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), IL-8 and myeloperoxidase (MPO) in mucosal tissues.
      RESULTS: Linear hemorrhagic mucosal lesions were observed primarily in the
      glandular stomach 4 h after oral administration of indomethacin. Pretreatment
      with irsogladine maleate markedly reduced the number and severity of these
      lesions in a dose-dependent manner. The mucosal concentrations of proinflammatory
      cytokines (TNF-alpha, IL-1beta, and IL-8) and MPO, which indicates the degree of
      mucosal infiltration by neutrophils, increased concomitantly with the occurrence
      of gastric injury in the indomethacin-treated rats. Pretreatment with irsogladine
      maleate significantly decreased the levels of these inflammatory factors in
      gastric tissue elicited by indomethacin. CONCLUSION: The mucosal protective
      effects afforded by irsogladine maleate on gastric injury induced by indomethacin
      are mediated by inhibition of mucosal proinflammatory cytokine production and
      neutrophil infiltration, leading to suppression of mucosal inflammation and
      subsequent tissue destruction.

PMID- 18720541
TI  - An anorectal fistula treatment with acellular extracellular matrix: a new
      technique.
AB  - AIM: To investigate a new technique of the anorectal fistula treatment with
      acellular extracellular matrix (AEM). METHODS: Thirty patients with anorectal
      fistula were treated with AEM. All fistula tracts and primary openings were
      identified using conventional fistula probe. All tracts were curetted with curet
      and irrigated with hydrogen peroxide and metronidazole. The AEM was pulled into
      the fistula tract from secondary to primary opening. The material was secured at
      the level of the primary opening. The excess AEM was trimmed at skin level at the
      secondary opening. RESULTS: All of the 30 patients had successful closure of
      their fistula after a 7-14 d follow-up. The healing rate of anal fistula in
      treatment group was 100%. The ache time, healing time and anal deformation of
      treatment group were obviously superior to traditional surgical methods.
      CONCLUSION: Using AEM anal fistula plug in treatment that causes the anorectal
      fistula is safe and successful in 100% of patients. It can reduce pain, shorten
      disease course and protect anal function.

PMID- 18720542
TI  - Prokinetic effects of a ghrelin receptor agonist GHRP-6 in diabetic mice.
AB  - AIM: To investigate the effects of a ghrelin receptor agonist GHRP-6 on delayed
      gastrointestinal transit in alloxan-induced diabetic mice. METHODS: A diabetic
      mouse model was established by intraperitoneal injection with alloxan. Mice were
      randomized into two main groups: normal mice and diabetic mice treated with GHRP
      6 at doses of 0, 20, 50, 100 and 200 microg/kg ip. Gastric emptying (GE),
      intestinal transit (IT), and colonic transit (CT) were studied in mice after they
      had a phenol red meal following injection of GHRP-6. Based on the most effective
      GHRP-6 dosage, atropine was given at 1 mg/kg for 15 min before the GHRP-6
      injection for each measurement. The mice in each group were sacrificed 20 min
      later and the percentages of GE, IT, and CT were calculated. RESULTS: Percentages
      of GE, IT, and CT were significantly decreased in diabetic mice as compared to
      control mice. In the diabetic mice, GHRP-6 improved both GE and IT, but not CT.
      The most effective dose of GHRP-6 was 200 microg/kg and atropine blocked the
      prokinetic effects of GHRP-6 on GE and IT. CONCLUSION: GHRP-6 accelerates delayed
      GE and IT, but has no effect on CT in diabetic mice. GHRP-6 may exert its
      prokinetic effects via the cholinergic pathway in the enteric nervous system, and
      therefore, has therapeutic potential for diabetic patients with delayed upper
      gastrointestinal transit.

PMID- 18720543
TI  - OB glue paste technique for establishing nude mouse human gastric cancer
      orthotopic transplantation models.
AB  - AIM: To establish nude mouse human gastric cancer orthotopic transplantation
      models using OB glue paste technique. METHODS: Using OB glue paste technique,
      orthopic transplantation models were established by implanting SGC-7901 and MKN
      45 human gastric cancer cell strains into the gastric wall of nude mice.
      Biological features, growth of the implanted tumors, the success rate of
      transplantation and the rate of auto-metastasis of the two models were observed.
      RESULTS: The success rates of orthotopic transplantation of the two models were
      94.20% and 96%. The rates of hepatic metastasis, pulmonary metastasis, peritoneal
      metastasis, lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%,
      48.43% and 57.97%, 30.83% and 36.96%, 67.30% and 84.06%, and 59.75% and 10.53%,
      respectively. The occurrence of ascites was 47.80% and 36.96%. CONCLUSION: OB
      glue paste technique is easy to follow. The biological behaviors of the nude
      mouse human gastric cancer orthotopic transplantation models established with
      this technique are similar to the natural processes of growth and metastasis of
      human gastric cancer, and, therefore, can be used as an ideal model for
      experimental research of proliferative metastasis of tumors.

PMID- 18720544
TI  - Risk factors for local recurrence of middle and lower rectal carcinoma after
      curative resection.
AB  - AIM: To explore the risk factors for local recurrence of middle and lower rectal
      carcinoma after curative resection. METHODS: Specimens of middle and lower rectal
      carcinoma from 56 patients who received curative resection at the Department of
      General Surgery of Guangdong Provincial People's Hospital were studied. A large
      slice technique was used to detect mesorectal metastasis and evaluate
      circumferential resection margin status. The relations between clinicopathologic
      characteristics, mesorectal metastasis and circumferential resection margin
      status were identified in patients with local recurrence of middle and lower
      rectal carcinoma. RESULTS: Local recurrence of middle and lower rectal carcinoma
      after curative resection occurred in 7 of the 56 patients (12.5%), and was
      significantly associated with family history (c2=3.929, P=0.047), high CEA level
      (c2=4.964, P=0.026), cancerous perforation (c2=8.503, P=0.004), tumor
      differentiation (c2=9.315, P=0.009) and vessel cancerous emboli (c2=11.879,
      P=0.001). In contrast, no significant correlation was found between local
      recurrence of rectal carcinoma and other variables such as age (c2=0.506,
      P=0.477), gender (c2=0.102, c2=0.749), tumor diameter (c2=0.421, P=0.516), tumor
      infiltration (c2=5.052, P=0.168), depth of tumor invasion (c2=4.588, P=0.101),
      lymph node metastases (c2=3.688, P=0.055) and TNM staging system (c2=3.765,
      P=0.152). The local recurrence rate of middle and lower rectal carcinoma was
      33.3% (4/12) in patients with positive circumferential resection margin and 6.8%
      (3/44) in those with negative circumferential resection margin. There was a
      significant difference between the two groups (c2=6.061, P=0.014). Local
      recurrence of rectal carcinoma occurred in 6 of 36 patients (16.7%) with
      mesorectal metastasis, and in 1 of 20 patients (5.0%) without mesorectal
      metastasis. However, there was no significant difference between the two groups
      (c2=1.600, P=0.206). CONCLUSION: Family history, high CEA level, cancerous
      perforation, tumor differentiation, vessel cancerous emboli and circumferential
      resection margin status are the significant risk factors for local recurrence of
      middle and lower rectal carcinoma after curative resection. Local recurrence may
      be more frequent in patients with mesorectal metastasis than in patients without
      mesorectal metastasis.

PMID- 18720545
TI  - Gastric cancer cell lines induced by trichostatin A.
AB  - AIM: To explore the effect of trichostatin A (TSA) on apoptosis and acetylated
      histone H3 levels in gastric cancer cell lines BGC-823 and SGC-7901. METHODS: The
      effect of TSA on growth inhibition and apoptosis was examined by MTT,
      fluorescence microscopy and PI single-labeled flow cytometry. The acetylated
      histone H3 level was detected by Western blot. RESULTS: TSA induced apoptosis in
      gastric cancer cell lines BGC-823 and SGC-7901 was in a dose and time-dependent
      manner. Apoptotic cells varied significantly between TSA treated groups (37.5
      ng/mL 72 h for BGC-823 cell line and 75 ng/mL 72 h for SGC-7901 cell line) and
      control group (0.85+/-0.14 vs 1.14+/-0.07, P=0.02; 0.94+/-0.07 vs 1.15+/-0.06,
      P=0.02). Morphologic changes of apoptosis, including nuclear chromatin
      condensation and fluorescence strength, were observed under fluorescence
      microscopy. TSA treatment in BGC-823 and SGC-7901 cell lines obviously induced
      cell apoptosis, which was demonstrated by the increased percentage of sub-G1
      phase cells, the reduction of G1-phase cells and the increase of apoptosis rates
      in flow cytometric analysis. The result of Western blot showed that the
      expression of acetylated histone H3 increased in BGC-823 and SGC-7901 TSA
      treatment groups as compared with the control group. CONCLUSION: TSA can induce
      cell apoptosis in BGC-823 and SGC-7901 cell lines. The expression of acetylated
      histone H3 might be correlated with apoptosis.

PMID- 18720547
TI  - Diagnostic and therapeutic role of endoscopic retrograde cholangiopancreatography
      in biliary rhabdomyosarcoma.
AB  - Biliary rhabdomyosarcoma (BRMS) is an uncommon childhood malignancy which has
      been managed surgically. We present a case of a 3-year-old boy with BRMS, in whom
      endoscopic retrograde cholangiopancreatography (ERCP) was successfully used both
      diagnostically and therapeutically, thus obviating the need for surgery and its
      attendant risks of morbidity and mortality. We conclude that ERCP is an effective
      alternative to surgery for BRMS in some patients.

PMID- 18720546
TI  - Diversity of Helicobacter pylori isolates in expression of antigens and induction
      of antibodies.
AB  - AIM: To obtain evidence for selection of antigens used in genetically engineered
      vaccine against Helicobacter pylori (H pylori). METHODS: Enzyme linked
      immunoabsorbent assay (ELISA) was established on the basis of recombinant protein
      antigens rUreB, rHpaA, rVacA, rCagA1, rNapA, rFlaA and rFlaB of H pylori to
      detect expression rates of the antigens in bacterial isolates as well as positive
      rates of the antibodies in sera from H pylori-infected patients. PCR was applied
      to the detection of carrying rates of the genes encoding antigens in the
      isolates. RESULTS: The outputs of rUreB, rHpaA, rVacA, rCagA1, rNapA, rFlaA and
      rFlaB were approximately 35%, 32%, 15%, 23%, 56%, 25% and 20% of the total
      bacterial proteins, respectively. One hundred and fifty-one strains of H pylori
      were isolated from 347 biopsy specimens of chronic gastritis, peptic ulcer or
      gastric adenocarcinoma, with a positive rate of 43.5%. All of the isolates
      expressed UreB, HpaA, FlaA and FlaB while 52.3%, 92.1% and 93.4% of the isolates
      expressed VacA, CagA and NapA, respectively. In the sera of 151 H pylori-infected
      patients, the positive rates of IgG antibodies against UreB, HpaA, VacA, CagA,
      NapA, FlaA and FlaB were 100%, 87.4%, 43%, 71.5%, 89.4%, 84.8% and 79.5%,
      respectively. Furthermore, the expression frequencies of VacA and NapA were found
      to be relative to the severity of gastric diseases (P=0.016 and P<0.0001,
      respectively). CONCLUSION: UreB antigen is the top option of developing
      genetically engineered vaccine against H pylori followed by NapA or HpaA.

PMID- 18720548
TI  - Pancreatic transection from blunt trauma associated with vascular and biliary
      lesions: a case report.
AB  - Major injuries of the pancreas may result in considerable morbidity and mortality
      when associated with vascular and visceral injuries. In such cases, a right
      diagnosis and a prompt surgical intervention are necessary to give a chance to
      the patient. We herein describe a case of blunt abdominal trauma in a 29-year-old
      man whose pancreatic rupture was associated with hepatic artery, splenic vein and
      extrahepatic bile duct damage. Immediate surgery was performed after computer
      tomograghy (CT), the haemorrhagic lesions dictat the emergency transfer to the
      operating room. Spleno-pancreatic resection was done with reconstruction of the
      hepatic artery, ligation of the splenic vein and a Roux-en-Y bilio-jejunal
      diversion. The early post-operative course was complicated by stenosis of the
      arterial reconstruction, which was treated by endovascular angioplasty followed
      by percutaneous drainage of symptomatic pseudocyst, rest and antibiotics.
      Finally, the patient was discharged and was alive without clinical problems at
      the time when we wrote this case report. The present case underlines the clinical
      relevance of vascular and visceral injuries associated with pancreatic trauma and
      the problems arising in the diagnostic evaluation and the surgical strategy of
      complex multiple visceral and vascular lesions in blunt abdominal trauma.

PMID- 18720549
TI  - Unexpected discovery of 2 cases of hepatocyte nuclear factor 1alpha-mutated
      infracentimetic adenomatosis.
AB  - We present 2 cases of hepatocyte nuclear factor 1alpha (HNF1alpha)-mutated
      adenomatosis, discovered for reasons unrelated to this disease, and identified
      using immunohistochemical methods. These new tools may further our understanding
      of the link between adenomas/adenomatosis subtypes and their complications, and
      their association with other abnormalities.

PMID- 18720550
TI  - Cerebral and pulmonary embolisms after transcatheter arterial chemoembolization
      for hepatocellular carcinoma.
AB  - A cerebral lipiodol embolism is an extremely rare complication of transcatheter
      arterial chemoembolization for hepatocellular carcinoma. We present a case of
      cerebral lipiodol embolism that occurred after the third arterial
      chemoembolization, report the clinical and radiological findings, and review the
      medical literature.

PMID- 18720551
TI  - Lobulated inflammatory myoglandular polyp in the ascending colon observed by
      magnifying endoscopy and treated with endoscopic polypectomy.
AB  - The patient was a 33-year-old man with hematochezia. Colonoscopy revealed a
      lobulated peduncular polyp with bleeding, about 40 mm in diameter, in the
      ascending colon. The polyp had both red and white components and a mosaic
      pattern. Magnifying observation revealed a red rugged surface component, and
      smooth white nodules with enlarged round or oval crypt openings. Endoscopic
      polypectomy was performed. Histological examination of the specimen revealed
      inflammatory granulation tissue in the lamina propria, proliferation of smooth
      muscle, and hyperplastic glands with cystic change. This polyp was diagnosed as
      inflammatory myoglandular polyp (IMGP). Lobulated-type IMGP in the ascending
      colon is rare.

PMID- 18720552
TI  - Laparoscopic cystogastrostomy for the treatment of pancreatic pseudocysts: a case
      report.
AB  - Pancreatic pseudocysts (PPs) are collections of pancreatic secretions that are
      lined by fibrous tissues and may contain necrotic debris or blood. The
      interventions including percutaneous, endoscopic or surgical approaches are based
      on the size, location, symptoms and complications of a pseudocyst. With the
      availability of advanced imaging systems and cameras, better hemostatic
      equipments and excellent laparoscopic techniques, most pseudocysts can be found
      and managed by laparoscopy. We describe a case of a 30-year-old male patient with
      a pancreatic pseudocyst amenable to laparoscopic cystogastrostomy. An incision
      was made through the anterior gastric wall to expose the posterior gastric wall
      in close contact with the pseudocyst using an ultrasonically activated scalpel.
      Then, another incision was made for cystogastrostomy to obtain complete and
      unobstructed drainage. The patient recovered well after operation and was symptom
      free during a 6-mo follow-up, suggesting that laparoscopic cystogastrostomy is a
      safe and effective alternative to open cystogastrostomy for minimally invasive
      management of PPs.

PMID- 18720553
TI  - Secondary BRCA1 and BRCA2 alterations and acquired chemoresistance.
AB  - Tumor suppressor BRCA1 and BRCA2 are frequently mutated in familial breast and
      ovarian cancer. More than ten percent of women with breast or ovarian cancer
      carry BRCA1 or BRCA2 (BRCA1/2) mutations. Cancers that arise in mutation carriers
      have often lost the wild-type allele through somatic alterations during tumor
      progression. BRCA1/2 play important roles in homologous recombination repair of
      DNA double-strand breaks. Because of this, BRCA1/2-deficient cancers often have a
      better response to DNA cross-linking agents such as platinum analogues and to
      poly(ADP-ribose) polymerase (PARP) inhibitors. However, over time, the majority
      of these BRCA1/2-deficient cancers become resistant and patients die from
      refractory diseases. Three recent studies demonstrated that acquired resistance
      to platinum analogues or PARP inhibitors in tumors carrying frame-shift BRCA1/2
      mutations came from restored BRCA1/2 expression and HR function due to secondary
      intragenic mutations that corrected the open reading frames of mutated BRCA1/2.

PMID- 18720554
TI  - Morphometric evaluation of the repair of critical-size defects using
      demineralized bovine bone and autogenous bone grafts in rat calvaria.
AB  - OBJECTIVE: To evaluate the repair of critical-size bone defects in rats treated
      with demineralized bovine bone (DBB) compared with autogenous bone (AB). MATERIAL
      AND METHOD: A bone defect of 8 mm in diameter was created in the calvaria of 50
      Rattus norvegicus, treated either with DBB or AB. Sub-groups of five rats of each
      group were killed at 7, 14, 21, 30 and 90 days post-operatively, and the skulls
      were removed and processed histologically. Histological sections were stained
      with hematoxylin and eosin. RESULT: Histological analysis showed complete closure
      of the defects with new bone at 90 days in group AB, and substitution of the
      biomaterial by fibrotic connective tissue in the DBB group at 21 days.
      Morphometric analysis showed that DBB was rapidly absorbed at 14 days, with its
      volume density decreasing from 47%+/-0.8% at 7 days to 1.2%+/-0.41% at 14 days.
      Subsequently, volume densities of the connective tissue and neoformed bone
      increased from 51.1%+/-11.17% to 86.8%+/-7.92% and from 1.9%+/-1.13% to 12%+/
      8.02%, respectively, for the same time interval. The volume density of AB
      particles did not change throughout the experimental periods, but the amount of
      new bone increased markedly between 7 and 90 days, from 4.5%+/-1.57% to 53.5%+/
      6.42% (P<0.05). CONCLUSION: DBB did not provide complete repair of the defects,
      with significantly less new bone formation than in the AB group.

PMID- 18720555
TI  - PARP inhibitor tilts cell death from necrosis to apoptosis in cancer cells.

PMID- 18720556
TI  - Cross-linked and non-cross-linked collagen barrier membranes disintegrate
      following surgical exposure to the oral environment: a histological study in the
      cat.
AB  - BACKGROUND: Early barrier membrane degradation may result in decreased bone
      formation in guided bone regeneration (GBR) procedures. The aim of this study was
      to evaluate the bio-degradation of cross-linked (CLM) and non-cross-linked (NCLM)
      collagen membranes experimentally exposed to the oral environment of study
      animals. METHODS: In eight cats, 48 surgical procedures were performed, three
      along each side of the palate: 24 full-thickness soft tissue perforations were
      made and 24 full-thickness mini-flaps were raised. CLM or NCLM discs were placed
      either under the perforations and peripheral mucosa and left exposed
      (experimental) or covered by the flaps (controls). The four treatment modalities
      were equally distributed among the eight animals. Block sections were retrieved
      at 7 and 28 days post-operatively, providing histological specimens (6 each) at 7
      and 28 days for each treatment modality. RESULTS: Histological observation
      revealed that CLM and NCLM remained intact in the control sites during the 28
      days. At 7 and 28 days, CLM appeared interrupted in three and two experimental
      sites, respectively, and were undetected in the remaining sites. NCLM were
      interrupted in two sites each at 7 and 28 days, and were undetected in the other
      sites. There was no statistical difference between control specimens and between
      CLM and NCLM of the different treatment modalities at 7 or 28 days. CONCLUSIONS:
      Both cross-linked and non-cross-linked membranes were resistant to tissue
      degradation and maintained continuity throughout the study. However, none of the
      membranes was resistant to degradation when exposed to the oral environment

PMID- 18720557
TI  - Evaluation of the marginal precision of one-piece complete arch titanium
      frameworks fabricated using five different methods for implant-supported
      restorations.
AB  - OBJECTIVE: The aim of the present work was to compare the marginal precision of
      titanium frameworks for a complete arch-fixed prosthesis fabricated using five
      different methods. METHODS: A prospective study was designed. Fifteen titanium
      frameworks for totally edentulous upper or lower jaws, each supported by five to
      nine implants, were assigned to five study groups, so as to have three frameworks
      in each group for each technique: (1) lost wax technique frameworks, (2) cast
      titanium sovrastructures laser welded to prefabricated titanium copings, (3)
      Procera Implant Bridge, (4) Cresco Ti System and (5) CAM StructSURE Precision
      Milled Bar. The microgap between the framework and the shoulders of implant
      analogues was measured on the master cast with a stereomicroscope at a
      magnification of 100 x at four different locations, yielding a total of 364 data
      points on 91 implants. Data were analyzed using an ANOVA and a Tukey post hoc
      test (P=<0.05). RESULTS: The mean values for the microgap were 78 microm (SD+/
      48) for lost wax technique frameworks, 33 microm (SD+/-19) for cast titanium
      sovrastructures laser welded to titanium copyings, 21 microm (SD+/-10) for the
      Procera implant bridge, 18 microm (SD+/-8) for the Cresco Ti System and 27 microm
      (SD+/-15) for the CAM StructSURE. The differences among the mean values were
      statistically significant (P<0.01 or P<0.05). The comparisons among groups 3, 4,
      and 5 and between groups 2 and 5 were not significant (P>0.05). CONCLUSION: The
      computer-aided procedures analyzed in the present study were able to produce a
      precision-fitting framework, with no significant differences among them and, at
      the same time, showed a greater precision compared with the traditional casting
      methods or with the use of prefabricated titanium copings. However, it should be
      noted that, even if group 2 frameworks were not as accurate as groups 3 and 4,
      cast titanium sovrastructures laser welded to prefabricated titanium copings
      showed significantly better marginal precision than the frameworks produced with
      the lost wax technique.

PMID- 18720558
TI  - [A 60-year-old man with heart failure, dry cough and elevated INR values].

PMID- 18720559
TI  - [Pharmacogenetics in practice].

PMID- 18720560
TI  - District nurses' involvement in pain care: a theoretical model.
AB  - AIM: To explore district nurses care of chronic pain sufferers and to create a
      theoretical model that can explain the variation in district nurses experiences
      when caring for these patients. BACKGROUND: Many people suffer from chronic pain,
      which greatly affects their wellbeing and causes physical suffering and
      psychosocial limitations. District nurses frequently meet patients who suffer
      from chronic pain and consequent problems. District nurses often feel powerless
      and ill-equipped, and they experience difficulties during interactions with these
      patients. METHOD: This is a qualitative study with a theory-generating approach.
      Data were collected from interviews with 20 district nurses in five focus groups.
      Interviews were taped, transcribed and then analysed as per the grounded theory
      method. RESULTS: The result is a theoretical model of district nurses'
      involvement in pain care. The model: (1) illustrates three main conditions in the
      care situation that influence district nurses' involvement in pain care and (2)
      explains the connection between how district nurses actively or passively detect
      and actively or passively respond to patients with pain problems. CONCLUSIONS:
      The model explains why district nurses sometimes feel powerless or ill-equipped
      in dealing with chronic pain problems. Insufficient conditions make it difficult
      for district nurses to become involved with pain problems and thus result in
      passive detection of and passive response to pain problems. Supporting patients
      to communicate their pain, collaboration with and involvement from other
      professionals regarding pain care, the organisation's guidelines and support for
      pain care and training in pain care are interventions that will contribute to
      district nurses' involvement in pain care. RELEVANCE TO CLINICAL PRACTICE:
      Through the model, chronic pain care can be better explained and understood;
      consequently chronic pain care can be improved. The model can be used in each,
      unique, case-study analysis. Nursing staff and students can also use the model as
      a basis for discussions about chronic pain sufferers.

PMID- 18720562
TI  - [25 millions underinsured Americans].

PMID- 18720561
TI  - The Norwegian version of the American Pain Society Patient Outcome Questionnaire:
      reliability and validity of three subscales.
AB  - AIMS AND OBJECTIVES: To examine some psychometric properties of the Norwegian
      version of the American Pain Society's Patient Outcome Questionnaire(APS-POQ-N).
      BACKGROUND: This study is part of an investigation of Norwegian orthopaedic
      surgical patients, where the overall aim is to evaluate the quality of
      postoperative pain management. Therefore, an adequate questionnaire on the
      quality of postoperative pain management was needed. METHODS: The sample included
      114 orthopaedic postoperative patients. The instrument consists of three main
      subscales, namely the modified Brief Pain Inventory(modified BPI subscale), the
      subscale on satisfaction with pain management(Satisfaction subscale) and the
      subscale on beliefs about pain management (Beliefs subscale), together with six
      single items about pain management. The reliability of these three main subscales
      was estimated using Cronbach's alpha coefficients and the construct validity was
      evaluated using principal-axis factor analysis with oblimin rotation. RESULTS:
      Face and content validity of the APS-POQ-N were satisfactory, while the modified
      BPI and the Beliefs subscales showed acceptable internal consistency but the
      Satisfaction subscale did not. Factor analyses yielded a three-factor solution
      for the modified BPI, a one-factor solution for the Satisfaction subscale and a
      two-factor solution for the Beliefs subscale. CONCLUSIONS: The APS-POQ-N appears,
      in general, to be an acceptable method of evaluating postoperative pain
      management in orthopaedic postoperative patients.However, the alpha value of the
      Satisfaction subscale was low, and thus the subscale is not recommended for this
      purpose.

PMID- 18720563
TI  - The future of orthopaedic research; an orthopaedic clinical research network.

PMID- 18720564
TI  - Proceedings and abstracts of the 1st ESH-EBMT training course on blood and marrow
      transplantation in children, June 6-9, 2007, Genova, Italy.

PMID- 18720565
TI  - Selected articles from the Annual Meeting of the Norwegian Neurological
      Association, 26-30 November 2007, Oslo, Norway.

PMID- 18720566
TI  - Proceedings of the XIIth International IUPAC Symposium on Mycotoxins and
      Phytotoxins, May 2007, Istanbul, Turkey.

PMID- 18720567
TI  - American Academy of Allergy Asthma & Immunology (AAAAI)--for immediate release,
      December 19, 2007.

PMID- 18720568
TI  - Making it stick....

PMID- 18720569
TI  - Making it stick....

PMID- 18720570
TI  - Burned-out, or forced out?

PMID- 18720571
TI  - Ditto to four letter-writers.

PMID- 18720572
TI  - Knowledge and attitudes regarding pain management among  nurses in Hong Kong
      medical units.
AB  - AIMS: To investigate knowledge levels and attitudes regarding pain management
      among nurses working in medical units in Hong Kong and factors that might
      influence their knowledge and attitudes. BACKGROUND: Pain, a common symptom for
      patients in medical units, can be relieved by effective pain management. Nurses
      have a vital role in implementing pain management effectively and must,
      therefore, have a solid foundation of knowledge and a positive attitude towards
      pain management. DESIGN: Cross-sectional study. METHODS: A self-administered
      survey including demographics and the nurses' knowledge and attitudes survey
      regarding pain-Chinese version (NKASRP-C) was completed by 143 nurses working at
      medical units in a public hospital. Descriptive statistics and stepwise
      regression were used in the data analysis. RESULTS: A deficit in knowledge and
      attitudes related to pain management was prominent (percentage of total score =
      47.72, range = 20-76%). Although nurses had developed appropriate attitudes
      towards pain management, discrepancies between practice and attitudes existed.
      Those with a higher percentage of correct scores in NKASRP-C had longer clinical
      working experience and applied knowledge of pain to their daily work.
      CONCLUSIONS: The findings of this study, identifying problems of inadequate
      knowledge and inappropriate attitudes regarding pain management, are of concern.
      A better understanding of the factors that affect such knowledge and attitudes
      and of the discrepancy between attitudes and practice, can provide useful
      information to be included in education programmes for nurses and to inform
      policy on the provision of pain management.

PMID- 18720573
TI  - Pain management: evaluating the effectiveness of an educational  programme for
      surgical nursing staff.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to assess the effectiveness of
      a pain management education programme in improving the nurses' knowledge about,
      attitude towards and application of relaxation therapy. BACKGROUND: Pain of
      surgical patients has long been an existing problem of health care. Nursing staff
      need to be educated continuously to develop the professional ability of pain
      management. METHODS: A quasi-study design with pre- and posttest and post- and
      posttest was used. Subjects were chosen from a medical centre in Taipei by
      convenience sampling. The total sample size of 81 was segregated into a study
      group of 42 and control group of 39 participants. The study group attended a
      seven-session pain management programme totalling 15 hours. The control group
      received no pain management training. Scaled measurements were taken on pain
      management knowledge and attitude and relaxation therapy practice. RESULTS: (1)
      Scores for pain management knowledge differed significantly between the two
      groups (F = 40.636, p = 0.001). (2) Attitudes towards pain management differed
      between the two groups (F = 8.328, p = 0.005) and remained stable over time (F =
      1.603, p = 0.205). (3) Relaxation therapy practice differed significantly between
      the two groups, with the study group better than the control group (F = 4.006, p
      = 0.049). (4) Relaxation therapy was applied to nearly all (97.5%) of the
      patients cared for by study group nurses. All of the instructed patients
      performed this technique one to three times per day postsurgery. CONCLUSIONS:
      Continuing education can improve nurses' knowledge about, attitude towards and
      behaviour of pain management. RELEVANCE TO CLINICAL PRACTICE: Results of this
      study could be used to guide the development and implementation of continuing
      education programmes for nursing staff to enhance patients' care knowledge and
      skills.

PMID- 18720575
TI  - Validation of neonatal tetanus elimination in Bangladesh by lot quality-assurance
      cluster sampling.

PMID- 18720574
TI  - Expression of caveolin-3 immunoreactivities in the developing sciatic nerve of
      the rat.
AB  - Caveolae are formed by the caveolin (CAV) family of proteins, CAV-1, -2, and -3.
      CAV-1 and -2 are co expressed in many cell types, whereas CAV-3 is muscle
      specific and mutation of the CAV-3 gene causes muscular dystrophy. CAV-3 has also
      been detected in brain astroglial cells and in peripheral nerves along with CAV
      1. Therefore, we sought to determine whether CAV-3 protein is expressed in
      developing peripheral nerves by using immunohistochemistry and reverse
      transcription-polymerase chain reaction (RT-PCR). We found that CAV-3
      immunoreactivities (IRs) were Localized in the myelin sheath during peripheral
      nerve development. CAV-3 IRs were intense during the early postnatal stage, but
      decreased as the peripheral nerves matured at postnatal weeks 3-5. CAV-3 mRNA
      expression was also markedly decreased during postnatal development. Because the
      expression pattern of CAV-3 IRs was opposite that of CAV-1 IRs. CAV-1 and -3
      might be involved in different phases of peripheral nerve myelination and play
      complementary roles in myelin maturation and peripheral nerve development.

PMID- 18720576
TI  - African Programme for Onchocerciasis Control--report on task force meeting, July
      2008.

PMID- 18720577
TI  - Bioinformatics. Preface.

PMID- 18720578
TI  - Global Healthgrid: e-science meets biomedical informatics. Foreword.

PMID- 18720579
TI  - Pulmonary hypertension in interstitial lung disease.
AB  - Pulmonary hypertension (PH) may complicate the course of many forms of advanced
      interstitial lung disease (ILD) and has been shown to portend a worse outcome.
      The aetiology of PH is likely multifactorial with variable contribution of
      factors amongst the different diseases. The most common such conditions include
      idiopathic pulmonary fibrosis, sarcoidosis, connective tissue disease-related ILD
      and pulmonary langerhans cell histiocytosis. Whether the course and impact of PH
      in these conditions can be modified by therapy requires further study.

PMID- 18720580
TI  - Special issue. Year in review: Communicable Disease Surveillance, NSW, 2007.

PMID- 18720581
TI  - Bug Breakfast in the Bulletin. Recreational water: surfing the bugs.

PMID- 18720583
TI  - Communicable Diseases Report, NSW, March and April 2008.

PMID- 18720582
TI  - Fact sheet: anthrax.

PMID- 18720584
TI  - Reply to Buckley O, Munk PL, Torreggiani WC. MRI of Marjolin's ulcer. AJR 2007;
      189:W171.

PMID- 18720586
TI  - [Maternal and child health: school health (4)--"dietary problems of children in
      the United States and approaches taken at schools].

PMID- 18720585
TI  - [Basis of clinical economics (12)].

PMID- 18720587
TI  - [Exercise-physical activities and public health (4): "physical activities and
      environmental factors"].

PMID- 18720588
TI  - [Proceedings of the 9th National Diabetology Symposium. Diabetes and the
      urogenital system. Hradec Kralove, 2007].

PMID- 18720589
TI  - [27th Internal Medicine Seminar. Martin, Slovak Republic, 2008. Abstracts].

PMID- 18720590
TI  - [Progress in treatment of malignant lymphoma].

PMID- 18720591
TI  - [Basis of malignant lymphoma. 1. Classification].

PMID- 18720592
TI  - [Basis of malignant lymphoma. 2. Etiological mechanism (gene abnormalities)].

PMID- 18720593
TI  - [Basis of malignant lymphoma. 3. Etiological mechanism (infection)].

PMID- 18720594
TI  - [Malignant lymphoma: diagnostic approach. 1. Pathological diagnosis].

PMID- 18720595
TI  - [Malignant lymphoma. Diagnostic approach. 2. Diagnostic imaging].

PMID- 18720596
TI  - [Malignant lymphoma. Diagnostic approaches. 3. Cell surface markers].

PMID- 18720597
TI  - [Malignant lymphoma. Diagnostic approaches. 4. Chromosome and gene examinations].

PMID- 18720598
TI  - [malignant lymphoma. Physiopathology and treatment. 1. Hodgkin's lymphoma].

PMID- 18720599
TI  - [Malignant lymphoma. Physiopathology and treatment. 2. Lymphoma of low grade
      malignancy].

PMID- 18720600
TI  - [Malignant lymphoma. Physiopathology and therapy. 3. Diffuse large B-cell
      lymphoma].

PMID- 18720601
TI  - [Malignant lymphoma. Physiopathology and treatment: 4. NK/T cell lymphoma].

PMID- 18720602
TI  - [Malignant lymphoma. Physiopathology and therapy. 5. Burkitt lymphoma].

PMID- 18720603
TI  - [Malignant lymphoma. Physiopathology and treatment. 6. Peripheral T cell
      lymphoma].

PMID- 18720604
TI  - [Malignant lymphoma. Current topics. 1. Antibody therapy].

PMID- 18720605
TI  - [Malignant lymphoma. Current topics. 2. Hematopoietic stem cell transplantation
      for malignant lymphoma].

PMID- 18720606
TI  - [Diagnosis and treatment of malignant lymphoma: discussion].

PMID- 18720607
TI  - [Prevention of recurrence of liver cancer].

PMID- 18720608
TI  - [HIV infection and neurological complications].

PMID- 18720609
TI  - [Treatment guideline for aplastic anemia and the actual status of its
      applications].

PMID- 18720610
TI  - [Clinical quiz: a 66-year-old man with hypercalcemia and pleural effusion].

PMID- 18720611
TI  - [The "minimum knowledge" necessary for primary care physician: keypoints in the
      care of dialysis patients].

PMID- 18720612
TI  - [Comprehensive internal medicine specialists desired by patients].

PMID- 18720613
TI  - [Easy-to-understand clinical deduction and methods for its teaching].

PMID- 18720614
TI  - A function of WHO is "to promote and conduct research in the field of health".

PMID- 18720615
TI  - National health research system mapping in 10 Eastern Mediterranean countries.
AB  - Health research systems in the Eastern Mediterranean Region are not well
      developed to generate and use knowledge to improve health, reduce inequity and
      contribute to economic development. This study aimed to provide core data on
      National Health Research Systems (NHRS) in 10 Eastern Mediterranean countries in
      order to inform actions to strengthen health research system governance and
      management. Whilst there were examples of good practice, few countries had a
      formal NHRS and many basic building blocks needed for an effective system had not
      been put in place. Although limited in focus, the study provides useful
      information for countries to initiate action to strengthen their NHRS.

PMID- 18720616
TI  - Risk of Mycobacterium tuberculosis infection in Somalia: national tuberculin
      survey 2006.
AB  - To estimate the annual risk of tuberculosis (TB) infection (ARTI) in Somalia a
      tuberculin survey was conducted in February/March 2006. Stratified cluster
      sampling was carried out within the 18 regions and 101 randomly selected primary
      schools. Tuberculin testing was done in 10 680 grade 1 schoolchildren. Transverse
      tuberculin reaction size was measured 72 hours later. The number of children with
      a satisfactory test read was 10 364. The overall BCG coverage was 54%. Based on
      frequency distribution of tuberculin reaction sizes, the ARTI in Somalia was
      estimated at 2.2% (confidence interval: 1.5%-3.2%). There was an annual decline
      of 2.6% comparing with a previous study in 1956.

PMID- 18720617
TI  - Case-finding tuberculosis patients: diagnostic and treatment delays and their
      determinants.
AB  - This study in the Syrian Arab Republic assessed the frequency and determinants of
      delays in diagnosis and treatment of new smear-positive tuberculosis cases at
      DOTS treatment centres. Among 800 patients, the mean delay due to patient care
      seeking behaviour was 52.7 days (range 15-698) and the health system delay before
      diagnosis was 24.8 days; thus the mean total delay before diagnosis was 77.6
      days. The mean delay from diagnosis to start of treatment was very short at 2.9
      days. Significant risk factors for total delay were: living far from the health
      facility, feeling a high degree of stigma, seeking initial care at a non-health
      care provider and having more than 1 health care encounter before diagnosis.

PMID- 18720618
TI  - Nosocomial pneumonia: risk factors, rates and trends.
AB  - This study aimed to estimate the rate of and risk factors for nosocomial
      pneumonia of patients admitted to hospitals in Taif, Saudi Arabia. A case-control
      study was conducted of 211 discharged patients with confirmed pneumonia and 633
      controls without pneumonia and a review was made of hospital records during 1999
      2003. Multiple logistic regression showed that duration of hospital stay, unit of
      admission, chronic obstructive pulmonary diseases, coma, nasogastric tube,
      endotracheal tube, debilitating diseases and mechanical ventilation were
      independently associated with increased risk of pneumonia. The mean incidence of
      overall nosocomial infection in the period 1999-2003 was 3 per 100 discharged
      patients, while the mean incidence of nosocomial pneumonia was 0.88.

PMID- 18720620
TI  - Increased isolation of Vibrio cholerae O1 serotype Inaba over serotype Ogawa in
      Pakistan.
AB  - Although the predominant Vibrio cholerae serotype in Pakistan is Ogawa and
      serotype Inaba is rare, there has been a significant increase in the isolation of
      Inaba in our referral laboratory in Karachi. This paper reports this observation
      and further analysis of previous cholera data from 1993 to 2005 to assess the
      trend of occurrence and resistance pattern of V. cholerae strains. From January
      to September 2005, 245/3292 (7.4%) specimens yielded growth of V. cholerae. Of
      these, 243 were serotype Inaba, outnumbering serotype Ogawa. This recent Inaba
      strain is 100% resistant to cotrimoxazole, 3% resistant to chloramphenicol and
      not resistant to ampicillin, tetracycline and ofloxacin. This sensitivity pattern
      is almost similar to that of the previous predominant serotype Ogawa.

PMID- 18720619
TI  - Antibacterial susceptibility of uropathogens in 3 hospitals, Sari, Islamic
      Republic of Iran, 2002-2003.
AB  - To determine the frequency and pattern of antibiotic susceptibility of
      uropathogens in urinary tract infection (UTI) from 3 university hospitals we
      carried out a retrospective review of urine culture and antibiotic sensitivity
      testing from symptomatic outpatients and inpatients during 2002-2003. Of 5600
      samples, 703 (12.6%) were culture positive, 38.7% of which were from hospitalized
      patients. Escherichia coli was the leading cause of UTI in both groups of
      patients. The rates and roles of other pathogens, including Pseudomonas spp.
      (5.3%-10.4%), Enterobacter spp. (0%-5.7%), Staphylococcus spp.) 5.4%-26.4%),
      differed in each hospital. Differences in antibacterial susceptibility patterns
      were observed. Ampicillin (82%-100%) and co-trimoxazole (50%-90%) resistance were
      the most frequent. Methicillin resistance in Staphylococcus spp. ranged from 17%
      to 60%.

PMID- 18720621
TI  - Factors associated with acute diarrhoea in children in Dhahira, Oman: a hospital
      based study.
AB  - To elucidate the bacterial etiology of childhood diarrhoea in Dhahira, 856
      children < 12 years admitted for diarrhoea to Ibri Regional Referral Hospital
      from 2000 to 2002 were studied. The mean age was 2.4 (SD 2.3) years; the majority
      (92.9%) were < 5 years. Bacterial etiology was found in 15.2% of cases; 10.6% due
      to Shigella and 2.1% to Salmonella. Sh. sonnei was the commonest Shigella
      serogroup isolated. Salmonella infection was significantly associated with
      cramps, while Shigella infection was associated with fever, bloody stools and
      cramps. Antibiotics were prescribed in 36.2% of cases and the resistance to the
      common antibiotics tested was low.

PMID- 18720622
TI  - Measles epidemiology and its implications for a vaccination programme in Oman.
AB  - To describe the epidemiology of measles in Oman and the implications for a
      vaccination programme, we conducted a retrospective record-based study from 1
      January 2000 to 31 December 2003 using data from the national epidemiological
      surveillance system. All cases notified as suspected measles during the study
      period were included. Of the 185 notified cases, 19.4% were confirmed measles
      positive. Blood samples for measles IgM were collected in 97.3% of cases. The
      mean age of measles cases was 8.0 (SD 10.7) years. The estimated overall
      incidence rate of measles for the study period was 0.53 per 100,000 person-years.
      Regression analysis indicated measles was significantly commoner among non-Omanis
      and children who had not been vaccinated.

PMID- 18720623
TI  - Rubella serology in pregnant women attending health centres of Tehran University
      of Medical Sciences.
AB  - This study was performed in 2003-05 to determine the serological status of a
      sample of pregnant women as a preliminary study for the rubella vaccination
      programme. Out of 965 pregnant women attending health centres affiliated to
      Tehran University of Medical Sciences for prenatal care, the estimated rubella
      immunity rate was 91.1% (95% CI: 89.3%-92.9%) and the nonimmunity rate was 8.9%
      (95% CI: 7.1%-10.7%). The rubella immunity rate differed in different areas of
      Tehran but not significantly so. However, there was a significant difference in
      the level of rubella immunity by the number of persons per household and by age,
      but no significant relationship with economic status, occupation or level of
      education.

PMID- 18720624
TI  - Patterns and determinants of maternity care in Damascus.
AB  - This descriptive study was designed to describe the patterns and determinants of
      maternity care among Syrian women living in Damascus. All 39 birth registers in 2
      large provinces were used to recruit 500 mothers of healthy newborns. Mothers
      were interviewed in their homes using a semistructured questionnaire.
      Multivariate analysis of the determinants of the frequency of use of antenatal
      care showed the following variables were significant: urban residence and visit
      to antenatal care in the 1st trimester. The significant variables for an early
      visit to antenatal care were the woman's level of education; being pregnant with
      the 1st baby; and number of visits to antenatal care. Being young (age < 20
      years) also correlated with early timing of the 1st antenatal visit.

PMID- 18720625
TI  - Assessment of women's satisfaction with reproductive health services in Urmia
      University of Medical Sciences.
AB  - We assessed women's satisfaction with the reproductive health services in the
      population laboratory of Urmia University of Medical Sciences in 2003. A random
      sample of 600 married women aged 15-49 years completed a satisfaction
      questionnaire based on Bruce's criteria. Overall 76.2% of women were satisfied
      and 15.8% were completely satisfied with the total reproductive health service;
      however 34.0% of women were unsatisfied or completely unsatisfied with their
      health care provider. Factors that needed be improved were: providing all modern
      contraception methods in the health centres; using educational materials (e.g.
      pamphlets and brochures) at reproductive health consultations; and improving
      information given to clients to ensure informed choice of family planning method.

PMID- 18720626
TI  - Implementing a quality improvement programme in a family planning centre in
      Monastir, Tunisia.
AB  - We aimed to improve the quality of family planning and reproductive health
      services in a family planning centre though implementation of a quality
      improvement programme. Clients were surveyed to identify quality-related
      problems. Health care teams then analysed the causes of the problems, developed
      solutions for 3 selected ones and established a quality assurance framework. The
      selected issues were: long waiting time at the centre; insufficient integration
      of family planning and reproductive health services; and lack of a holistic
      approach. The final phase was aimed at testing and implementing corrective
      measures.

PMID- 18720627
TI  - Outcome and management of pregnancy in women with thalassaemia in Cyprus.
AB  - We describe the management and clinical outcome of pregnancies among 100 Greek
      Cypriot women with thalassaemia: 88 with thalassaemia major and 12 with
      thalassaemia intermedia. A total of 152 successful pregnancies and 161 deliveries
      were included. All patients had endocrine assessment and frequent ferritin
      measurements. Multiple successful pregnancies included 7 twins and 1 triple
      pregnancy. Pregnant thalassaemics required significantly larger amount of total
      blood transfusion during pregnancy. There was a statistically significant
      increase in the ferritin levels during pregnancy, and levels remained
      significantly higher after pregnancy. Most pregnancies resulted in delivery of
      full-term healthy babies, and obstetric complications were rare, although some
      problems were encountered.

PMID- 18720628
TI  - An audit of diabetes care at 3 centres in Alexandria.
AB  - Selected indicators for structure, process and outcome of care were used to audit
      diabetes care in 3 centres in Alexandria. Structure was poor: main problems
      included absence of appointment and recall system, deficiencies in laboratory
      resources and lack of educational material. Process of care was poor for 69.2% of
      patients: deficiencies included absence of essential information in records and
      missing some essential clinical examinations. Degree of control was poor for
      49.2% of patients and only 30.6% had no complications. Compliance to appointment
      was good for about 80% of patients. Better outcome (fewer complications and
      higher compliance) was significantly associated with poor process of care. This
      cannot, however, be considered a valid predictor of outcome as good care might be
      initiated by the presence of complications.

PMID- 18720629
TI  - Association of diabetes mellitus and dyslipidaemias in the Tehran population.
AB  - The aim of this survey was to evaluate the role of diabetes in the lipid profiles
      of the Tehran population. Measurements were carried out on 10 136 people aged 20
      69 years for blood sugar, triglycerides, total cholesterol, LDL cholesterol, and
      HDL cholesterol and data were collected on medical history, physical activity,
      smoking and obesity. The prevalence of any type of dyslipidaemia in the whole
      group was 68.5% and of diabetes mellitus was 11.0% (10.6% in men and 11.3% in
      women). The prevalence of dyslipidaemia in diabetics was 88.9%. There was strong
      association between diabetes mellitus and dyslipidaemia (P < 0.05). In regression
      analysis, diabetes was the second most important factor after obesity in
      secondary dyslipidaemia.

PMID- 18720630
TI  - Periodontal status of type 2 diabetics compared with nondiabetics in north
      Jordan.
AB  - The periodontal status of 106 type 2 diabetic patients was assessed and compared
      with that of 106 age-matched nondiabetics. Patients older than 20 years with type
      2 diabetes mellitus were recruited from the outpatient internal medicine clinics
      at the 2 main hospitals in Irbid governorate, Jordan. Periodontal disease was
      more severe in type 2 diabetic patients than in nondiabetics, as indicated by
      significantly mean higher gingival index, periodontal pocket depth, clinical
      attachment level and tooth mobility. There was no significant difference in the
      mean plaque index between diabetics and nondiabetics. The severity of periodontal
      disease was significantly higher in patients with diabetes > 5 years than those
      with duration < 5 years.

PMID- 18720631
TI  - [Programme for improving emotional and cognitive changes in patients under renal
      dialysis in Egypt].
AB  - We investigated the effect of chronic renal failure on the emotional status,
      social and psychological adaptation and the cognitive status of patients and the
      effect of a programme to improve the psychosocial state of the patients; 40 renal
      dialysis patients and 40 healthy controls were included. We used the Emotional
      Status Scale, Psychosocial Adaptation Scale, the Primary Mental Abilities Test
      and the Memory Processes Scale for assessment of the participants. The controls
      had better emotional/cognitive status and psychosocial adaptation than the
      dialysis patients, a statistically significant difference. There were also
      statistically significant differences between the patients before and after the
      application of the programme.

PMID- 18720632
TI  - Attitudes of dental students towards using computers in education--a mixed design
      study.
AB  - This mixed design study explored attitudes of dental students towards use of
      computers. It employed quantitative analyses of a questionnaire answered by 979
      students and qualitative analysis of suggestions by a subgroup of 339. Positive
      attitudes towards computers were predicted by "computer use for > 1 year" and
      "year of study". Qualitative analysis of students' suggestions confirmed these
      findings and brought up new issues such as the need for establishing a website
      for the faculty. The results indicate that careful planning is needed to improve
      students' skills and incorporate computer applications in educational curricula.

PMID- 18720633
TI  - [Attitudes of Tunisian medical students to medical practice: gender differences].
AB  - To better understand the impact of gender change in medical practice on health
      care in Tunisia, we conducted a cross-sectional study on the attitudes of 512
      medical students (40% female) to medicine and medical practice in the Faculty of
      Medicine, Sousse. Female students attached more value than males to the intrinsic
      aspects of a physician's job, such as the desire to help others and to work with
      people. Regarding the dimensions of comprehensive care (psychosociological
      aspects of care, health education, patient-centred approach and medical
      prevention), there were wide differences between men and women. At the end of
      their training cycles, both male and female students ascribed less importance to
      these aspects than in the beginning.

PMID- 18720634
TI  - Occupational stress and work-related unintentional injuries among Iranian car
      manufacturing workers.
AB  - This study in 2004 and 2005 aimed to present the pattern of job stress among car
      manufacturing workers in one factory in the Islamic Republic of Iran, and to
      assess its relationship with occupational injuries. Data were collected from 608
      male workers (508 at-risk general workers and 100 with injuries in the last
      year). Job stress was assessed by the Belkic occupational stress index. The
      prevalence of job stress was 21.3%. The main occupational stressors were time
      pressure (78.5%), mode of payment and evaluation (56.4%), and interaction with
      people and machines (41.3%). The risk of injury among those with job stress was
      significantly higher than those without job stress (OR = 2.0; 95% CI: 1.20-3.30).
      Job stress was responsible for 11.9% of all occupational injuries in this group.

PMID- 18720635
TI  - Sport practice among private secondary-school students in Dubai in 2004.
AB  - A study was made of sport practice and of knowledge, attitude and practice
      towards sport among 1475 private secondary-school students in Dubai, United Arab
      Emirates (UAE) in 2004. UAE students practised sport more than non-UAE students
      (33.9% versus 18.7% had good levels of activity) but there was no significant
      difference in positive attitudes towards sport practice (87.1% and 86.2%
      respectively). A good level of sport (vigorous exercise > or = 3 times per week
      for 20 min) was higher among males (26.0%) than females (14.7%). There was a
      significant association between overweight and obesity as well as tobacco smoking
      and low levels of sport practice. Health education intervention is needed to
      improve sport practice among young people.

PMID- 18720636
TI  - Ten-year mortality from Creutzfeldt-Jakob disease in Cyprus.
AB  - We report the mortality from sporadic Creutzfeldt-Jakob disease in Cyprus for a
      10-year surveillance period (1995-2004). In that time, 5 cases were identified
      out of a population of 749,000, giving an incidence of 0.7 cases per million
      population per year. Our sporadic incidence matches that expected according to
      global epidemiological surveillance. No cases of variant Creutzfeldt-Jakob
      disease were found but 1 familial case was diagnosed.

PMID- 18720637
TI  - Maternal mortality in Bahrain 1987-2004: an audit of causes of avoidable death.
AB  - The aim of this report was to establish the national maternal mortality rate in
      Bahrain over the period 1987-2004, to identify preventable factors in maternal
      deaths and to make recommendations for safe motherhood. There were 60 maternal
      deaths out of 243 232 deliveries giving an average maternal mortality rate of
      24.7 per 100 000 total births. The main causes of death were sickle-cell disease
      (25.0%), hypertension (18.3%), embolism (13.3%), haemorrhage (13.3%), heart
      disease (11.7%), infection (8.3%) and other (10.0%). In an audit of care, 17
      (28.3%) out of 60 deaths were judged to be avoidable, nearly half of which were
      due to a shortage of intensive care beds. We recommend that a confidential
      enquiry of maternal deaths be conducted at the national level every 3 to 5 years.

PMID- 18720638
TI  - Introducing the IMCI community component into the curriculum of the Faculty of
      Medicine, University of Gezira.
AB  - In 2001 the Faculty of Medicine of the University of Gezira (FMUG) started to
      introduce the Integrated Management of Childhood Illness (IMCI) strategy into its
      medical curriculum. The emphasis was on pre-service training that addresses
      standard case management and the IMCI community component. This report presents
      the experience of FMUG in integrating such a training package into the medical
      curriculum. It explains the rationale for introducing the IMCI community
      component and the guiding principles for doing so. It describes the community
      based courses into which the community component was integrated, the
      implementation and impact of the programme and the constraints faced.

PMID- 18720639
TI  - Perforated tuberculous appendicitis and peritoneal tuberculosis.

PMID- 18720640
TI  - Alkaptonuria in a 5-year-old boy in Iraq.

PMID- 18720641
TI  - Community health.

PMID- 18720642
TI  - RAC reviews: are you ready?

PMID- 18720643
TI  - Revenue cycle management starts at registration.

PMID- 18720644
TI  - Measuring performance, not activity, key to A/R success.

PMID- 18720645
TI  - [Frequency and manifestations of back pain in the dental profession].
AB  - Dentists, dental hygienists and dental assistants due to the nature of their work
      related physical activity often have to deal with physical stress that will cause
      actual physical damage. The aim of the current survey was to analyse the
      frequency of job-related pain and associated impairment. The questionnaire for
      the cervical and lumbal region of the North American Spine Society was modified
      and used in the present investigation. Out of 6962 subjects, 2025 returned the
      questionnaire (response rate 34.5%). Between 20% and 36% of the participants
      suffered from pain in the cervical and lumbal region and were impaired in their
      daily activities, particularly during the lifting of objects, while standing or
      sleeping. Almost 40% of the dentists and 53% of the dental hygienists/dental
      assistants experienced problems related to perceived pain during or after dental
      treatments. More than half of the participants had already sought out medical
      help and/or physiotherapy due to job-related pain. The present data indicate that
      prophylactic and therapeutically based preventative measures should be encouraged
      in order to prevent cervical and back pain in this affected occupational group.

PMID- 18720646
TI  - [Intraoral placement of a fiberglass-reinforced composite bridge].
AB  - A 16 year-old female patient was introduced to the Department of Restorative
      Dentistry after having completed orthodontic treatment. She suffered from the
      missing of the lateral incisivi. Aim of the treatment was to replace the missing
      teeth of the growing patient with atraumatic and minimal-invasive technique. With
      a pre-impregnated fibreglass ribbon and with the aid of a special matrix
      technique the teeth were replaced as fibreglass ribbon resin-bonded bridges with
      a direct laminating technique using an "Esthetic Composite", including
      opakdentine, dentine and enamel compounds as well as special compounds for
      effects like lustre. An esthetically satisfying result could be achieved with the
      tooth-preserving methods available at the moment.

PMID- 18720647
TI  - [Necrotizing sialometaplasia: diagnosis of a rare entity].
AB  - A differential diagnosis of an ulcer on the hard palate must consider a wide
      variety of diseases and conditions, among them rare entities such as necrotizing
      sialometaplasia. We report the case of a patient who presented with a painful
      ulcer on the hard palate. A biopsy taken at the initial presentation of the
      patient revealed a diagnosis of necrotizing sialometaplasia. Histology showed
      foci of eosinophilic granulocytes with lobular infarction or necrosis, bland
      appearing nuclear morphology of squamous cells, simultaneous metaplasia of ducts
      and mucous acini. The ulcer resolved spontaneously within seven weeks and
      required no specific treatment. The case presented here shows that early
      diagnosis of necrotizing sialometaplasia is important in order to prevent
      unnecessary treatment.

PMID- 18720648
TI  - Uncertainties in the current knowledge of some atmospheric trace gases associated
      with U.S. agriculture: a review.
AB  - Approximately 80 different crop species are grown in the United States in widely
      differing geographic areas, climatic and edaphic conditions, and management
      practices. Although the majority of cultivated acreage in the United States is
      planted with only about 10 primary crops, uncertainties associated with trace gas
      emissions arise from: (1) limited data availability, (2) inaccurate estimates
      because of large temporal and spatial variability in trace gas composition and
      magnitude of trace gas emissions from agricultural activities, (3) differing
      characteristics of pollutant emissions from highly dispersed animal feed-lots,
      and (4) limited understanding of the emissions of semi-volatile organic compounds
      (SVOCs) associated with agriculture. Although emission issues are of concern, so
      also is atmospheric deposition to cropping systems, including wet and dry
      nitrogen, minerals, and organic compounds. These can have feedback effects on
      trace gas emissions. Overall, the many gaps in our understanding of these aspects
      of agricultural systems deserve serious attention.

PMID- 18720649
TI  - Characterization of particulate matter for three sites in Kuwait.
AB  - Many studies have shown strong associations between particulate matter (PM)
      levels and a variety of health outcomes, leading to changes in air quality
      standards in many regions, especially the United States and Europe. Kuwait, a
      desert country located on the Persian Gulf, has a large petroleum industry with
      associated industrial and urban land uses. It was marked by environmental
      destruction from the 1990 Iraqi invasion and subsequent oil fires. A detailed
      particle characterization study was conducted over 12 months in 2004-2005 at
      three sites simultaneously with an additional 6 months at one of the sites. Two
      sites were in urban areas (central and southern) and one in a remote desert
      location (northern). This paper reports the concentrations of particles less than
      10 microm in diameter (PM10) and fine PM (PM2.5), as well as fine particle
      nitrate, sulfate, elemental carbon (EC), organic carbon (OC), and elements
      measured at the three sites. Mean annual concentrations for PM10 ranged from 66
      to 93 microg/m3 across the three sites, exceeding the World Health Organization
      (WHO) air quality guidelines for PM10 of 20 microg/m3. The arithmetic mean PM2.5
      concentrations varied from 38 and 37 microg/m3 at the central and southern sites,
      respectively, to 31 microg/m3 at the northern site. All sites had mean PM2.5
      concentrations more than double the U.S. National Ambient Air Quality Standard
      (NAAQS) for PM2.5. Coarse particles comprised 50-60% of PM10. The high levels of
      PM10 and large fraction of coarse particles comprising PM10 are partially
      explained by the resuspension of dust and soil from the desert crust. However,
      EC, OC, and most of the elements were significantly higher at the urbanized
      sites, compared with the more remote northern site, indicating significant
      pollutant contributions from local mobile and stationary sources. The particulate
      levels in this study are high enough to generate substantial health impacts and
      present opportunities for improving public health by reducing airborne PM.

PMID- 18720650
TI  - Assessing energy, environmental, and economic tradeoffs in intermodal freight
      transportation.
AB  - This paper presents an energy and environmental network analysis model to explore
      tradeoffs associated with freight transport. The geospatial model uses an
      intermodal network built by the authors to connect various modes (rail, road,
      water) via intermodal terminals. Routes along the network are characterized not
      only by temporal and distance attributes, but also by cost, energy, and emissions
      attributes (including emissions of carbon dioxide, particulate matter, sulfur
      oxides, volatile organic compounds, and oxides of nitrogen). Decision-makers can
      use the model to explore tradeoffs among alternative route selection across
      different modal combinations, and to identify optimal routes for objectives that
      feature energy and environmental parameters (e.g., minimize carbon dioxide
      emissions). The model is demonstrated with three case studies of freight
      transport along the U.S. eastern seaboard.

PMID- 18720651
TI  - Metal oxides remove hydrogen sulfide from landfill gas produced from waste mixed
      with plaster board under wet conditions.
AB  - Hydrogen sulfide (H2S) is a major odorant in landfills. We have studied H2S
      production from landfill residual waste with and without sulfur-containing
      plaster board, including the influence of the water content in the waste. The
      laboratory experiments were conducted in 30-L polyethylene containers with a
      controlled water level. We also studied how different materials removed H2S in
      reactive layers on top of the waste. The organic waste produced H2S in
      concentrations of up to 40 parts per million (ppm) over a period of 80 days. When
      plaster board was added, the H2S concentration increased to 800 ppm after a lag
      period of approximately 40 days with a high water level, and to approximately 100
      ppm after 50 days with a low water level. The methane (CH4) concentration in the
      initial experiment was between 5 and 70% after 80 days. The CH4 concentration in
      the second experiment increased to nearly 70% in the container with a high water
      level, slowly declining to approximately 60% between days 20 and 60. The CH4
      concentrations during the experiments resembled normal landfill concentrations.
      Metallic filter materials were very efficient in removing H2S, whereas organic
      filter materials showed poor H2S removal.

PMID- 18720652
TI  - Multimedia emissions inventory of polychlorinated biphenyls for the U.S. Great
      Lakes states.
AB  - Polychlorinated biphenyls (PCBs) were banned in the United States in 1979, and
      since then a significant decline in their release to the environment has been
      observed. This decline has now reached a plateau. Several new regulatory programs
      have been put in place to further reduce PCB emissions/releases. However, our
      ability to measure the effectiveness of these regulatory/voluntary programs and
      to support regional fate/transport and source/receptor modeling efforts depend on
      reliable emission information. In this study, we attempt to improve the emission
      inventory for PCBs by compiling and analyzing the multimedia total PCB
      emission/release data reported for the U.S Great Lakes states for each year from
      1990 to 2000. Although Toxic Release Inventory (TRI), National Emissions
      Inventory (NEI), Great Lakes Regional Air Toxic Emissions Inventory (GLRATEI),
      and Integrated Atmospheric Deposition Network (IADN) data formed the basis of
      estimating air emissions, we used the TRI, National Response Center (NRC), and
      PCB transformer inventory data to estimate PCB releases to land. We used the
      Permit Compliance System and NRC data to obtain estimates of PCB discharges to
      water systems in the Great Lakes states. The Remedial Action Plans for each area
      of concern were the primary source for estimating PCB loads of dredged sediments.
      On the basis of the NEI, IADN, and GLRATEI data, the total air emissions within
      the decade were approximately 126 t. The regionwide discharges to water systems
      and releases to land in the form of landfills and accidental spills in 1990-2000
      were estimated as approximately 170 and 3225 t, respectively. We estimated that
      approximately 1.3 million t of PCB-contaminated sediment were removed or targeted
      for removal in five lakes of the U.S. portion of the Great Lakes basin. We stress
      that these estimates were based on reported amounts and the unreported PCB
      releases/emissions could result in significantly higher estimates.

PMID- 18720653
TI  - Real-world in-use activity, fuel use, and emissions for nonroad construction
      vehicles: a case study for excavators.
AB  - A study design was developed and demonstrated for deployment of a portable
      emission measurement system (PEMS) for excavators. Excavators are among the most
      commonly used vehicles in construction activities. The PEMS measured nitric
      oxide, carbon monoxide, hydrocarbons, carbon dioxide, and opacity-based
      particulate matter. Data collection, screening, processing, and analysis
      protocols were developed to assure data quality and to quantify variability in
      vehicle fuel consumption and emissions rates. The development of data collection
      procedures was based on securing the PEMS while avoiding disruption to normal
      vehicle operations. As a result of quality assurance, approximately 90% of the
      attempted measurements resulted in valid data. On the basis of field data
      collected for three excavators, an average of 50% of the total nitric oxide
      emissions was associated with 29% of the time of operation, during which the
      average engine speed and manifold absolute pressure were significantly higher
      than corresponding averages for all data. Mass per time emission rates during non
      idle modes (i.e., moving and using bucket) were on average 7 times greater than
      for the idle mode. Differences in normalized average rates were influenced more
      by intercycle differences than intervehicle differences. This study demonstrates
      the importance of accounting for intercycle variability in real-world in-use
      emissions to develop more accurate emission inventories. The data collection and
      analysis methodology demonstrated here is recommended for application to more
      vehicles to better characterize real-world vehicle activity, fuel use, and
      emissions for nonroad construction equipment.

PMID- 18720654
TI  - Direct measurement of fugitive emissions of hydrocarbons from a refinery.
AB  - Refineries are a source of emissions of volatile hydrocarbons that contribute to
      the formation of smog and ozone. Fugitive emissions of hydrocarbons are difficult
      to measure and quantify. Currently these emissions are estimated based on
      standard emission factors for the type and use of equipment installed.
      Differential absorption light detection and ranging (DIAL) can remotely measure
      concentration profiles of hydrocarbons in the atmosphere up to several hundred
      meters from the instrument. When combined with wind speed and direction, downwind
      vertical DIAL scans can be used to calculate mass fluxes of the measured gas
      leaving the site. Using a mobile DIAL unit, a survey was completed at a Canadian
      refinery to quantify fugitive emissions of methane, C2+ hydrocarbons, and benzene
      and to apportion the hydrocarbon emissions to the various areas of the refinery.
      Refinery fugitive emissions as measured with DIAL during this demonstration study
      were 1240 kg/hr of C2+ hydrocarbons, 300 kg/hr of methane, and 5 kg/hr of
      benzene. Storage tanks accounted for over 50% of the total emissions of C2+
      hydrocarbons and benzene. The coker area and cooling towers were also significant
      sources. The C2+ hydrocarbons emissions measured during the demonstration
      amounted to 0.17% of the mass of the refinery hydrocarbon throughput for that
      period. If the same loss were repeated throughout the year, the lost product
      would represent a value of US$3.1 million/yr (assuming US$40/bbl). The DIAL
      measured hourly emissions of C2+ hydrocarbons were 15 times higher than the
      emission factor estimates and gave a different perspective on which areas of the
      refinery were the main source of emissions. Methods, such as DIAL, that can
      directly measure fugitive emissions would improve the effectiveness of efforts to
      reduce emissions, quantify the reduction in emissions, and improve the accuracy
      of emissions data that are reported to regulators and the public.

PMID- 18720655
TI  - A modeling study of coarse particulate matter pollution in Beijing: regional
      source contributions and control implications for the 2008 Summer Olympics.
AB  - In the last 10 yr, Beijing has made a great effort to improve its air quality.
      However, it is still suffering from regional coarse particulate matter (PM10)
      pollution that could be a challenge to the promise of clean air during the 2008
      Olympics. To provide scientific guidance on regional air pollution control, the
      Mesoscale Modeling System Generation 5 (MM5) and the Models-3/Community
      Multiscale Air Quality Model (CMAQ) air quality modeling system was used to
      investigate the contributions of emission sources outside the Beijing area to
      pollution levels in Beijing. The contributions to the PM10 concentrations in
      Beijing were assessed for the following sources: power plants, industry, domestic
      sources, transportation, agriculture, and biomass open burning. In January, it is
      estimated that on average 22% of the PM10 concentrations can be attributed to
      outside sources, of which domestic and industrial sources contributed 37 and 31%,
      respectively. In August, as much as 40% of the PM10 concentrations came from
      regional sources, of which approximately 41% came from industry and 31% from
      power plants. However, the synchronous analysis of the hourly concentrations,
      regional contributions, and wind vectors indicates that in the heaviest pollution
      periods the local emission sources play a more important role. The implications
      are that long-term control strategies should be based on regional-scale
      collaborations, and that emission abatement of local sources may be more
      effective in lowering the PM10 concentration levels on the heavy pollution days.
      Better air quality can be attained during the Olympics by placing effective
      emission controls on the local sources in Beijing and by controlling emissions
      from industry and power plants in the surrounding regions.

PMID- 18720656
TI  - Emissions from carpet combustion in a pilot-scale rotary kiln: comparison with
      coal and particle-board combustion.
AB  - The use of post-consumer carpet as a potential fuel substitute in cement kilns
      and other high-temperature processes is being considered to address the problem
      of huge volumes of carpet waste and the opportunity of waste-to-energy recovery.
      Carpet represents a high volume waste stream, provides high energy value, and
      contains other recoverable materials for the production of cement. This research
      studied the emission characteristics of burning 0.46-kg charges of chopped nylon
      carpet squares, pulverized coal, and particle-board pellets in a pilot-scale
      natural gas-fired rotary kiln. Carpet was tested with different amounts of water
      added. Emissions of oxygen, carbon dioxide, nitric oxide (NO), sulfur dioxide
      (SO2), carbon monoxide (CO), and total hydrocarbons and temperatures were
      continuously monitored. It was found that carpet burned faster and more
      completely than coal and particle board, with a rapid volatile release that
      resulted in large and variable transient emission peaks. NO emissions from carpet
      combustion ranged from 0.06 to 0.15 g/MJ and were inversely related to CO
      emissions. Carpet combustion yielded higher NO emissions than coal and particle
      board combustion, consistent with its higher nitrogen content. SO2 emissions were
      highest for coal combustion, consistent with its higher sulfur content than
      carpet or particle board. Adding water to carpet slowed its burn time and reduced
      variability in the emission transients, reducing the CO peak but increasing NO
      emissions. Results of this study indicate that carpet waste can be used as an
      effective alternative fuel, with the caveats that it might be necessary to wet
      carpet or chop it finely to avoid excessive transient puff emissions due to its
      high volatility compared with other solid fuels, and that controlled mixing of
      combustion air might be used to control NO emissions from nylon carpet.

PMID- 18720657
TI  - Effects of driving conditions on diesel exhaust particulates.
AB  - Four driving conditions were examined to characterize how speeds and loads of a
      medium-duty diesel engine affect resultant diesel exhaust particulates (DEPs) in
      terms of number concentrations (< or =400 nm), size distribution, persistent free
      radicals, elemental carbon (EC), and organic carbon (OC). At the medium engine
      load (60%), DEPs surged in number concentrations at around 40-70 nm, whereas DEPs
      from the full engine load (100%) showed a distinctive bimodal distribution with a
      large population of 30-50 nm and 100-400 nm. Under the full engine load, engine
      speeds insignificantly affected resultant DEP number concentrations. When the
      engine load decreased from 100% to the medium level (60%), DEPs of ultrafine size
      and 100-400 nm decreased at least 1.4 times (from 5.6 x 10(8) to 4 x 10(8) #/cm3)
      and more than 3 times (from 2.7 x 10(8) to 0.8 x 10(8) #/cm3), respectively. The
      same reduction in the engine load significantly decreased persistent free
      radicals in DEPs up to approximately 30 times (from 123 x 10(16) to 4 x 10(16)
      #spin/g). Decreasing the engine load from 100 to 60% also concurrently reduced
      both EC and OC in total DEPs around 2 times, from 27.3 to 13.9 mg/m3, and from
      17.6 to 9.2 mg/m3, respectively. For DEPs smaller than 1 microm, under the full
      engine load, EC and OC consistently peaked at 170-330 nm under an engine speed of
      1800 rpm or 94-170 nm under an engine speed of 3000 rpm, reflecting processes of
      nucleation, cluster-cluster agglomeration, and condensation. Decreasing the
      engine load from 100 to 60% reduced EC and OC in DEPs (smaller than 1 microm) at
      least 3 times (0.6 to 0.2 mg/m3) and 2 times (0.4 to 0.2 mg/m3), respectively.
      Taken together, decreasing the full engine load to a medium (60%) level
      effectively reduced the number concentrations (< or =400 nm), persistent free
      radicals, EC, and OC of total DEPs, as well as the concentration of EC and OC in
      ultrafine and accumulation-mode DEPs.

PMID- 18720658
TI  - Rethinking the assessment of photochemical modelin systems in air quality
      planning applications.
AB  - The U.S. Environmental Protection Agency provides guidelines for demonstrating
      that future 8-hr ozone (O3) design values will be at or below the National
      Ambient Air Quality Standards on the basis of the application of photochemical
      modeling systems to simulate the effect of emission reductions. These guidelines
      also require assessment of the model simulation against observations. In this
      study, we examined the link between the simulated relative responses to emission
      reductions and model performance as measured by operational evaluation metrics, a
      part of the model evaluation required by the guidance, which often is the
      cornerstone of model evaluation in many practical applications. To this end,
      summertime O3 concentrations were simulated with two modeling systems for both
      2002 and 2009 emission conditions. One of these two modeling systems was applied
      with two different parameterizations for vertical mixing. Comparison of the
      simulated base-case 8-hr daily maximum O3 concentrations showed marked model-to
      model differences of up to 20 ppb, resulting in significant differences in
      operational model performance measures. In contrast, only relatively minor
      differences were detected in the relative response of O3 concentrations to
      emission reductions, resulting in differences of a few ppb or less in estimated
      future year design values. These findings imply that operational model evaluation
      metrics provide little insight into the reliability of the actual model
      application in the regulatory setting (i.e., the estimation of relative changes).
      In agreement with the guidance, it is argued that more emphasis should be placed
      on the diagnostic evaluation of O3-precursor relationships and on the development
      and application of dynamic and retrospective evaluation approaches in which the
      response of the model to changes in meteorology and emissions is compared with
      observed changes. As an example, simulated relative O3 changes between 1995 and
      2007 are compared against observed changes. It is suggested that such
      retrospective studies can serve as the starting point for targeted diagnostic
      studies in which individual aspects of the modeling system are evaluated and
      refined to improve the characterization of observed changes.

PMID- 18720659
TI  - Theoretical evaluation of a method for locating gaseous emission hot spots.
AB  - This paper describes and theoretically evaluates a recently developed method that
      provides a unique methodology for mapping gaseous emissions from non-point
      pollutant sources. The horizontal radial plume mapping (HRPM) methodology uses an
      open-path, path-integrated optical remote sensing (PI-ORS) system in a horizontal
      plane to directly identify emission hot spots. The radial plume mapping
      methodology has been well developed, evaluated, and demonstrated. In this paper,
      the theoretical basis of the HRPM method is explained in the context of the
      method's reliability and robustness to reconstruct spatially resolved plume maps.
      Calculation of the condition number of the inversion's kernel matrix showed that
      this method has minimal error magnification (EM) when the beam geometry is
      optimized. Minimizing the condition number provides a tool for such optimization
      of the beam geometry because it indicates minimized EM. Using methane
      concentration data collected from a landfill with a tunable diode laser
      absorption spectroscopy (TDLAS) system, it is demonstrated that EM is minimal
      because the averaged plume map of many reconstructed plume maps is very similar
      to a plume map generated by the averaged concentration data. It is also shown in
      the analysis of this dataset that the reconstructions of plume maps are unique
      for the optimized HRPM beam geometry and independent of the actual algorithm
      applied.

PMID- 18720660
TI  - Barriers to formal drug abuse treatment in the rural south: a preliminary
      ethnographic assessment.
AB  - This article describes barriers to obtaining drug abuse treatment in the rural
      South using qualitative interviews conducted with 86 illicit stimulant users
      recruited in rural Arkansas and Kentucky between 2003 and 2005. Fifty-nine
      (69.0%) of the interviewees had never entered drug abuse treatment. Sixteen
      (19.0%) participants reported current perceived need for treatment, while seven
      (8%) were ambivalent about seeking it. Interview data suggest five interrelated
      categories of barriers to accessing drug abuse treatment: (1) geographical, (2)
      organizational, (3) economic, (4) social, and (5) psychological. The study
      findings can inform further examination of rural treatment barriers and have
      important implications for developing strategies to overcome these obstacles.

PMID- 18720661
TI  - Predicting positive and negative treatment responses to stimulants with brain
      SPECT imaging.
AB  - The goal of this study was to test whether clinician-rated regional cerebral
      blood flow (rCBF) as rendered by SPECT imaging is a meaningful predictor of
      patient response to CNS stimulants. Chart reviews were used to identify patients
      who reported prior significant positive and negative responses to CNS stimulants.
      Each patient in the study had received resting and concentration SPECT scans
      using Tc99m exametazime. Differences in cerebral blood flow for frontal regions
      of interest were assessed in three conditions (resting, concentration, and their
      difference, or "delta") using ANCOVAs and age-matched ANOVAs. Prefrontal pole
      deltas were found to be highly sensitive and specific predictors of response to
      CNS stimulants, with pole activation predicting adverse responses and pole
      deactivation predicting good responses. Positive and negative predictive values
      were greater than .75 for both poles. We conclude that SPECT renderings of rCBF,
      particularly in the prefrontal cortex, are a potentially powerful clinical tool
      for anticipating response to stimulant medications, both positive and adverse.

PMID- 18720662
TI  - Preliminary evidence differentiating ADHD using brain SPECT imaging in older
      patients.
AB  - The objective of this study was to differentiate ADHD patients from a healthy
      comparison group using high resolution brain SPECT imaging in older patients.
      Using extensive chart reviews of structured interviews, DSM-IV criteria, and
      psychiatrist-given diagnoses, we identified 27 patients over age 50 with ADHD,
      either combined or inattentive types. Patients were compared to an age-matched
      group of healthy subjects with brain SPECT imaging at rest and during
      concentration using semiquantitative visual readings. Significantly lower
      cortical activity is noted in the ADHD group, particularly in the prefrontal
      poles, orbits, and parietal lobes. Older ADHD patients can be discerned from
      healthy subjects using brain SPECT. The results support the executive dysfunction
      model of ADHD.

PMID- 18720663
TI  - Characteristics of injection drug users who participate in drug dealing:
      implications for drug policy.
AB  - So-called "balanced" drug policy couples enforcement initiatives targeting drug
      dealers with health-focused interventions serving addicted individuals. There are
      few evaluations of this approach, and little is known about how these two
      populations may overlap. We evaluated factors associated with drug dealing among
      injection drug users (IDUs) in Vancouver, Canada, and examined self-reported drug
      dealing roles and reasons for dealing. Among 412 IDUs seen from March through
      December 2005, 68 (17%) had dealt drugs during the previous six months. Variables
      independently associated with drug dealing included: recent incarceration
      (adjusted odds ratio [AOR] = 2.9; 95%CI: 1.4-6.0); frequent heroin injection (AOR
      = 2.5; 95%CI: 1.4-4.6); frequent cocaine injection (AOR = 2.0; 95%CI: 1.1-3.8);
      and recent overdose (AOR = 2.7; 95%CI: 1.0-7.3). The most common drug-dealing
      roles were direct selling (82%), middling (35%), and steering (19%), while the
      most common reasons for dealing included obtaining drugs (49%) and money (36%).
      Drug dealing among IDUs was predicted by several markers of higher intensity
      addiction, and drug-dealing IDUs tended to occupy the most dangerous positions in
      the drug-dealing hierarchy. These findings suggest that elements of "balanced"
      drug policies may undermine each other and indicate the need for alternative
      interventions.

PMID- 18720664
TI  - A clean and sober place to live: philosophy, structure, and purported therapeutic
      factors in sober living houses.
AB  - The call for evidence-based practices (EBPs) in addiction treatment is nearly
      universal. It is a noteworthy movement in the field because treatment innovations
      have not always been implemented in community programs. However, other types of
      community-based services that may be essential to sustained recovery have
      received less attention. This article suggests that sober living houses (SLHs)
      are a good example of services that have been neglected in the addiction
      literature that might help individuals who need an alcohol- and drug-free living
      environment to succeed in their recovery. It begins with an overview of the
      history and philosophy of this modality and then describes our five-year
      longitudinal study titled, "An Analysis of Sober Living Houses." Particular
      attention is paid to the structure and philosophy of SLHs and purported
      therapeutic factors. It ends with the presentation of baseline data describing
      the residents who enter SLHs and six-month outcomes on 130 residents.

PMID- 18720665
TI  - The link between recent sexual abuse and drug use among African American male
      college students: it's not just a female problem in and around campus.
AB  - This study examined the relationship between sexual abuse in or around campus and
      drug use among young African-American males in college. It offers cross-sectional
      analysis of data collected from the Alcohol and Substance Abuse Awareness and Use
      Study (ASAAUS). Data collection took place in October 2004 via a self
      administered survey among 181 African-American male students. Males who reported
      past sexual abuse in or around campus were significantly more likely than
      nonsexually-abused males to have used tobacco (41% v. 19%, p < .05), alcohol (82%
      v. 49%, p < .05), marijuana (59% v. 30%, p < .05), and cocaine (18% v. 2%, p <
      .05) in the 30 day preceding the interview. Logistic regression analyses
      indicated that sexual abuse history in or around campus was significantly
      associated with past year (OR = 9.8, p < or = 0.001) and past 30 day (OR = 5.0, p
      < or = 0.001) drug use.

PMID- 18720666
TI  - Listening to our clients: the prevention of relapse.
AB  - A survey to assess the most common reasons for relapse was developed and
      administered to 335 individuals who were current clients in various levels of
      care in a large substance abuse treatment program in order to better understand
      what factors were most relevant for relapse among these clients. Several reasons
      for relapse were chosen significantly more often than others. Common reasons for
      relapse for both men and women were the following: feeling bored, feeling anxious
      or stressed, wanting to use and get high, believing that use could occur without
      getting readdicted, and relationship problems and break up. In addition, men also
      commonly reported anger, having too much money, and no longer attending meetings
      as significant reasons for relapse. Among female clients, depression, loneliness,
      and the pain of withdrawal were among their top reasons for relapse. As a result
      of this survey, specific groups were developed and implemented in an effort to
      better address the unique reasons for relapse that our clients most commonly
      reported. It is hoped that the addition of these groups will help to improve
      overall treatment outcome of the clients who are served by the agency.

PMID- 18720667
TI  - Enhancing adolescent substance abuse treatment engagement.
AB  - Trends in adolescent drug use are encouraging and suggest the importance of
      preventative programs for youth. Yet, among those who become involved with
      illicit substances and seek treatment, only a fraction report positive outcomes.
      This article describes an approach to enhance adolescent participation in
      substance abuse treatment. Aspects of the transtheoretical model are integrated
      into a treatment program designed to meet the unique developmental needs of
      adolescent alcohol and marijuana abusers. The result is a treatment that better
      engages adolescents in participation, thereby increasing the likelihood for
      treatment success.

PMID- 18720668
TI  - Legally high? Legal considerations of Salvia divinorum.
AB  - The legal status of the hallucinogenic plant Salvia divinorum has been rapidly
      changing. Legal prohibitions on this plant native to Oaxaca, Mexico have emerged
      at the state level, a phenomenon that has not occurred since the passage of the
      Controlled Substances Act (CSA). Included will be a brief description of the
      plant that has only recently crept into the popular American consciousness, and a
      review of the different legal mechanisms through which states have controlled the
      plant and the pending legislation proposing controls. Lastly, the implications of
      various state laws are discussed.

PMID- 18720669
TI  - The "vine of the soul" vs. the Controlled Substances Act: implications of the
      hoasca case.
AB  - In 2006, the Supreme Court paved the way for the sacramental use of a
      hallucinogen, hoasca, to be imported, distributed and ingested by a religious
      group. This case has broad implications for religious freedom for using
      sacramental psychotropics and how such cases might be decided in the future. This
      article outlines the arguments used both by the church and by the government. It
      lists the facts of the cases, explains and analyzes the decision, evaluates the
      likelihood of expansions of religion-based exceptions for entheogen use in light
      of the Supreme Court's decision and offers a profile for those groups most likely
      to receive such an exemption.

PMID- 18720670
TI  - Substance use problems reported by historically Black college students: combined
      marijuana and alcohol use versus alcohol alone.
AB  - Using secondary data analysis,this study compares alcohol and other drug (AOD)
      problems experienced by African-American students attending a historically Black
      university who use alcohol only versus those who use alcohol plus marijuana.
      Results indicate that students who used marijuana plus alcohol experienced more
      AOD problems than their counterparts who used alcohol only. The current findings
      are similar to previous research with a majority White college student
      population.

PMID- 18720671
TI  - Neuropsychological effects of formaldehyde use.
AB  - This study compared five individuals who intentionally ingested formaldehyde
      (possibly laced with PCP) in marijuana cigarettes to a control group on measures
      of cognitive ability. Formaldehyde, a major component in embalming fluid, is
      legal to purchase and possess and has become popular due to its euphoric
      properties. In significant doses, the chemical is a neurotoxin. The effects of
      inadvertent exposure are fairly well known, but the effects of intentional
      ingestion have only recently been investigated. In addition, there has been
      little research on the effects of formaldehyde use specific to intellectual
      ability and cognitive intactness. The results of this study indicate intentional
      ingestion may cause a decline in neuropsychological intactness, as measured by
      performance on the Shipley Institute of Living Scale.

PMID- 18720672
TI  - Chloroquine psychosis masquerading as PCP: a case report.
AB  - Chloroquine and its derivatives have been drugs of choice in the prophylaxis and
      treatment of malaria for over 50 years. These drugs are also frequently used in
      the treatment of various rheumatologic disorders. Because many Americans now
      travel abroad and may require chloroquine prophylaxis, as well as the fact that
      such medications are readily available through Internet-based supply houses,
      clinicians should be aware of the potential toxicity associated with the use of
      these agents. We present the case of an adolescent female who presented with
      acute, chloroquine-induced toxic psychosis resembling that induced by
      phencyclidine (PCP) in clinical presentation and laboratory findings. In the
      acute setting, the differentiation between chloroquine toxic psychosis and PCP
      psychosis may be difficult. Therefore, the syndrome of chloroquine-induced
      psychosis is reviewed and its differentiation from PCP psychosis highlighted as
      it relates to important aspects of this case.

PMID- 18720673
TI  - A case report of propofol dependence in a physician.
AB  - Propofol is a widely used general anaesthetic with multisite mechanisms and
      especially ultrashort activation of certain central GABA-A receptors. Since its
      introduction into the market in the mid 1980s this is the seventh report on
      propofol dependence in the literature. The present case shows for the first time
      that craving for propofol can be quite intense and able to induce addictive
      behaviour.

PMID- 18720674
TI  - Ecstasy analogues found in cacti.
AB  - Human interest in psychoactive phenethylamines is known from the use of mescaline
      containing cacti and designer drugs such as Ecstasy. From the alkaloid
      composition of cacti we hypothesized that substances resembling Ecstasy might
      occur naturally. In this article we show that lophophine, homopiperonylamine and
      lobivine are new minor constituents of two cactus species, Lophophora williamsii
      (peyote) and Trichocereus pachanoi (San Pedro). This is the first report of
      putatively psychoactive phenethylamines besides mescaline in these cacti. A
      search for further biosynthetic analogues may provide new insights into the
      structure-activity relationships of mescaline. An intriguing question is whether
      the new natural compounds can be called "designer drugs."

PMID- 18720675
TI  - Physician practices and information management. HIM professionals offer value in
      changing practices.

PMID- 18720676
TI  - Home sweet medical home. Can a new care model save family medicine?

PMID- 18720677
TI  - Weighing the Stark Law exceptions.

PMID- 18720678
TI  - Certified EHRs. Certification reduces risk and effort in product selection.

PMID- 18720679
TI  - In search of quality quality initiatives. High interest, high obstacles in
      designing quality improvement programs.

PMID- 18720680
TI  - Quality data and documentation for EHRs in physician practice.

PMID- 18720681
TI  - Healthcare manager's work is never done.

PMID- 18720682
TI  - Interview with Mark Howard, FACHE, recipient of the 2008 ACHE Gold Medal Award.
      Interview by Kyle L Grazier.

PMID- 18720683
TI  - Imagining seamless healthcare transactions.

PMID- 18720684
TI  - Managers and the new definition of quality.
AB  - The manager, particularly the mid-level manager, has a vital role in the success
      of any healthcare organization, especially in the realm of patient perception of
      quality. To patients, "quality" means how well a service was delivered, not how
      technically superior the actual service or clinical component turned out. This
      definition of quality can also be referred to as patient satisfaction. Managers,
      with help of an integrative team, can develop quality processes geared toward
      patient expectations by doing a number of things, including the following:
      clearly identify outcomes, and empower employees to achieve those goals; form an
      integrated quality development team to establish quality metrics; build in
      cultural competence into quality processes; and align the organization's mission
      to the overall quality program. With a successful quality program, managers can
      expect a considerable return on investment, satisfied patients and staff, and
      improved clinical outcomes.

PMID- 18720685
TI  - Provider and policy response to reverse the consequences of low health literacy.
AB  - The 2004 Institute of Medicine publication, Health Literacy: A Prescription to
      End Confusion, is the first comprehensive report about low health literacy and
      its consequences. Although affecting more than 50 percent of the adult population
      in the United States, low health literacy is a pervasive issue that has received
      little attention among policymakers and healthcare executives. Yet, strategies to
      increase the health literacy of patient communities are relatively inexpensive
      and easy to implement. Furthermore, such strategies have the potential to
      significantly reduce costs and improve outcomes by arming the population with
      information on self-management and prevention of disease. This article presents
      an overview of the issues surrounding low health literacy, highlights its impact
      on the delivery system, and discusses practical steps that healthcare providers
      and executives can implement to enable health literate communities.

PMID- 18720686
TI  - Advertising expenditures in the nursing home sector: evaluating the need for and
      purpose of advertising.
AB  - Marketing and advertising activities in the nursing home sector have increased in
      recent years, following the example of hospitals and health systems. The reasons
      for this trend may be related to the growth in competition but are not clearly
      identified yet. Theoretically, advertising becomes necessary to gain an advantage
      over the competition. The purpose of this study was to identify the reasons for
      the variation in advertising expenditures among nursing homes in Texas. For this
      study, we merged 2003 data from the Texas Medicaid Nursing Facility Cost Report,
      the Texas Nursing Home Quality Reporting System, and the Area Resource File for
      Texas. Using the Herfindahl-Hirschman Index, we then examined the correlations
      between advertising expenses and the level of market concentration. We evaluated
      the association between advertising expenditures and market competition using two
      logistic and four linear regression models. Total advertising expenses in Texas
      nursing homes ranged from $0 to $165,000 per year. Higher advertising
      expenditures were associated with larger facilities, higher occupancy, and high
      Medicare census. Market competition, however, was not a significant predictor of
      such expenses. Advertising seems to be more resource-driven than market-driven.
      Therefore, some advertising expenditures may be unnecessary, may lack impact, and
      may even be wasteful. Reducing unnecessary advertising costs could free up
      resources, which may be allocated to necessary resident care activities.

PMID- 18720687
TI  - The COA360: a tool for assessing the cultural competency of healthcare
      organizations.
AB  - The U.S. Census Bureau projects that by 2050, non-Hispanic whites will be in the
      numerical minority. This rapid diversification requires healthcare organizations
      to pay closer attention to cross-cultural issues if they are to meet the
      healthcare needs of the nation and continue to maintain a high standard of care.
      Although scorecards and benchmarking are widely used to gauge healthcare
      organizations' performance in various areas, these tools have been underused in
      relation to cultural preparedness or initiatives. The likely reason for this is
      the lack of a validated tool specifically designed to examine cultural
      competency. Existing validated cultural competency instruments evaluate
      individuals, not organizations. In this article, we discuss a study to validate
      the Cultural Competency Organizational Assessment--360 or the COA360, an
      instrument designed to appraise a healthcare organization's cultural competence.
      The Office of Minority Health and the Joint Commission have each developed
      standards for measuring the cultural competency of organizations. The COA360 is
      designed to assess adherence to both of these sets of standards. For this
      validation study, we enlisted a panel of national experts. The panel rated each
      dimension of the COA360, and the combination of items for each of the scale's 14
      dimensions was rated above 4.13 (on 5-point scale). Our conclusion points to the
      validity of the COA360. As such, it is a valuable tool not only for assessing a
      healthcare organization's cultural readiness but also for benchmarking its
      progress in addressing cultural and diversity issues.

PMID- 18720688
TI  - From the emergency department to the general hospital: hospital ownership and
      market factors in the admission of the seriously mentally ill.
AB  - General hospitals are becoming the safety net provider for the seriously mentally
      ill (SMI) in the United States, but these patients are faced with a number of
      potential barriers when accessing these hospitals. Hospital ownership and market
      forces are two potential organizational and healthcare system barriers that may
      affect the SMI patient's access, because the psychiatric and medical services
      they need are unprofitable services. This study examines the relationship among
      hospital ownership, market forces, and admission of the SMI patient from the
      emergency department into the general hospital. This was a cross-sectional study
      of a large sample of SMI patients from the 2002 State Inpatient Datasets for five
      states. Multiple logistic regression was applied in the multivariable analysis.
      After controlling for patient, hospital, and county covariates and when compared
      with not-for-profit hospitals, public hospitals were more likely to admit while
      investor-owned hospitals were less likely to admit SMI patients. Hospitals in
      competitive markets were less likely to admit while hospitals with capitation
      revenues were slightly less likely to admit these patients. Policy options that
      can address this "market failure" include strengthening the public psychiatric
      inpatient care system, making private health insurance coverage of the SMI more
      equitable, revising Medicare prospective payment system to better reimburse the
      treatment of the SMI, and allowing not-for-profit hospitals to count care of the
      SMI as a community benefit. Results of this study will be useful to healthcare
      managers searching for ways to reduce unnecessary administrative costs while
      continuing to maintain the level of administrative activities required for the
      provision of safe, effective, and high-quality care.

PMID- 18720689
TI  - Doxycycline plus levamisole: combination treatment for severe nodulocystic acne.
AB  - BACKGROUND: Levamisole is an agent without much potential use alone, but through
      immunomodulation, may synergistically improve the efficacy of other drugs like
      doxycycline in the treatment of acne vulgaris. OBJECTIVE: The goal of this study
      was to determine the efficacy of levamisole in addition to doxycycline in the
      treatment of patients suffering from severe nodulocystic acne. METHODS: A double
      blind, randomized, placebo-controlled trial was conducted in the dermatology
      clinic of Rasoul-e-Akram Hospital in Tehran, Iran in 2006. Sixty patients were
      randomly assigned to 1 of 2 study groups. The case group was administered oral
      levamisole 2.5 mg/kg/wk (up to 150 mg/wk) plus doxycycline 100 mg daily and the
      control group was given 100 mg of oral doxycycline daily and a placebo. Patients
      were evaluated at baseline, and at 2-month, 4-month, and 6-month checkpoints.
      RESULTS: The responses to treatment were significantly higher in the case group
      according to the reduction in total lesions count, acne severity index; and
      papule/pustule and nodule/cyst count at the 2nd, 3rd, and 4th visits. CONCLUSION:
      Results indicated that adding oral levamisole to doxycycline is an effective
      treatment for severe nonresponsiveness to conventional treatments of acne
      vulgaris. In the patient group, levamisole was well tolerated with an acceptable
      safety profile. At the time of publication, this study is the first clinical
      trial that suggests levamisole as an effective new treatment for severe acne
      vulgaris.

PMID- 18720690
TI  - Long-term safety of mycophenolate mofetil and cyclosporine: a review.
AB  - The prevailing notion in dermatology is that mycophenolate mofetil (MMF) is safer
      than cyclosporine (CsA), but that CsA has greater efficacy. This literature
      review evaluates the available long-term safety data of MMF and CsA. Literature
      in the fields of dermatology, autoimmune disease, and transplantation were
      retrieved from PubMed. Data regarding immunosuppressive and non-immunosuppressive
      side effects of MMF and CsA are presented along with available pregnancy safety
      data. Surprisingly, there is a paucity of data on long-term MMF monotherapy.
      Transplant data is presented separately due to the concomitant use of other
      immunosuppressants along with MMF. Trends that can be identified include a less
      discernable cancer or end-organ damage risk in MMF compared to CsA. However, MMF
      appears to have a greater risk in pregnancy and increased reports of herpes
      simplex and zoster infection compared to CsA.

PMID- 18720691
TI  - Prevalence of community-acquired methicillin-resistant Staphylococcus aureus in a
      private dermatology office.
AB  - BACKGROUND: The prevalence of community-acquired methicillin-resistant
      Staphylococcus aureus (CA-MRSA) skin and soft tissue infection (SSTI) in private
      practice dermatology office is largely unknown and the prescribing of antibiotic
      treatment could be influenced by such data. OBJECTIVE: Investigators sought to
      examine the period prevalence of CA-MRSA infections involving skin and soft
      tissue in a suburban private practice dermatology setting. METHODS: Chart reviews
      of 170 patients who had bacterial cultures taken from January 2007 to November
      2007 were performed, with an analysis of sex, age, immune status, species of
      growth, type of lesion, and culture site. RESULTS: The mean age of the study
      population was 54.0 years (SD 21.8) and 51.1 % were male. Of the 170 cultures
      taken, 135 (79%) grew 1 or more bacteria and MRSA positive cultures were found in
      28 (21%) of 135 cultures. LIMITATIONS: Only 1 geographic location was
      represented. CONCLUSION: The rising rates of CA-MRSA skin and soft tissue
      infections should be evaluated with consideration of the unique populations that
      the majority of reports represent. There is little doubt that the prevalence of
      skin infections caused by CA-MRSA have increased dramatically and will likely
      continue to do so in the future. However, the authors caution the empiric
      prescribing of antibiotics presently known to be effective against CA-MRSA and
      advocate the culturing of all infectious lesions upon presentation and reserve
      these antibiotics (tetracyclines, trimethoprim-sulfamethoxazole [TMP-SMX],
      clindamycin, rifampin) for the treatment of high-risk patients and patients with
      culture proven CA-MRSA infections.

PMID- 18720692
TI  - Evaluating the tolerability and efficacy of etanercept compared to triamcinolone
      acetonide for the intralesional treatment of keloids.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory and
      profibrotic cytokine that inhibits degradation of collagen and
      glycosaminoglycans. Etanercept, a recombinant TNF-alpha receptor fusion protein,
      may decrease excessive fibrous tissue in keloids. OBJECTIVE: To evaluate the
      tolerability and efficacy of etanercept as compared to triamcinolone acetonide
      (TAC) for the treatment of keloids. METHODS: Twenty subjects were randomly
      assigned to receive monthly intralesional injections of either 25 mg of
      etanercept or 20 mg of TAC for 2 months. Keloids were evaluated at baseline, week
      4, and week 8 by subjects and investigators in a blinded fashion using physical,
      clinical, and cosmetic parameters. Photographs were taken and adverse events were
      noted during each evaluation. RESULTS: Etanercept improved 5/12 parameters
      including significant pruritus reduction, while TAC improved 11/12 parameters at
      week 8, although no statistical difference was observed as compared to baseline.
      There was no significant difference between the 2 treatment groups. Both
      treatments were safe and well tolerated. CONCLUSION: Etanercept was safe, well
      tolerated, improved several keloid parameters, and reduced pruritus to a greater
      degree than TAC therapy. However, further studies are required before it can be
      recommended for the treatment of keloids.

PMID- 18720693
TI  - The effectiveness of liquid bandage as an adhesive and antimicrobial agent.

PMID- 18720694
TI  - A case series of 48 patients treated with thalidomide.
AB  - INTRODUCTION: Thalidomide is approved by the Food and Drug Administration (FDA)
      for erythema nodosum leprosum, but has been used in many other dermatological
      conditions that are refractory to standard therapy. METHODS: The medical records
      of 48 patients treated with thalidomide at Baylor College of Medicine (Houston,
      TX) were retrospectively reviewed to determine the conditions treated with
      thalidomide, dosing, efficacy, treatment duration, side effects, adverse events,
      and reason for discontinuing therapy. RESULTS: Forty-eight patients (men = 18,
      women = 30) with a mean age of 49.6 years (range: 20-79) were included in this
      study. Patients were treated for prurigo nodularis, discoid lupus erythematosus,
      tumid lupus erythematosus, subacute cutaneous lupus erythematosus, systemic lupus
      erythematosus, lichen planus, lichen planopilaris, cutaneous sarcoidosis, and
      prurigo nodularis. All conditions were refractory to standard therapy. Patients
      were treated for a mean of 7.5 months (range: 3 days to 70 months). In most of
      the disorders, a majority of patients experienced clinical improvement. The most
      common reason for discontinuation of therapy was side effects, the most frequent
      being peripheral neuropathy. LIMITATIONS: This study was limited by being
      retrospective in nature. CONCLUSION: Thalidomide effectively treats some
      dermatologic conditions that are refractory to standard medications. There are
      inconveniences associated with obtaining the medication and it is expensive.
      Physicians must be vigilant for possible side effects, especially peripheral
      neuropathy.

PMID- 18720695
TI  - Low risk of postinflammatory hyperpigmentation in skin types 4 and 5 after
      treatment with fractional CO2 laser device.
AB  - BACKGROUND/OBJECTIVE: Hyperpigmentation occurs in more than 37% of dark-skinned
      subjects treated with a fully ablative CO2 laser device. This study assessed the
      risk of postinflammatory hyperpigmentation (PIH) in subjects with skin types 4
      and 5 treated once with a specific protocol of treatment using a fractional CO2
      laser. METHODS: Seven subjects with photodamaged skin received a single facial
      treatment using a fractional CO2 laser. Anesthesia was limited to a lidocaine and
      prilocaine cream for 1 hour before the single-pass treatment. Subjects were
      evaluated for improvement and PIH on alternate days for 14 days, and at 1 month,
      3 months, and 6 months posttreatment. RESULTS: All subjects achieved improvement
      in their specific skin conditions and in skin texture. Postinflammatory
      hyperpigmentation was not observed in any subject. Four subjects experienced no
      pain during treatment, while 3 reported mild pain. Recovery was associated with
      minimal pain and itching. CONCLUSION: In dark-skinned subjects, fractional CO2
      laser treatment and topical anesthesia subjectively improves common skin
      conditions without PIH.

PMID- 18720696
TI  - The use of acellular, fetal bovine dermal matrix for acute, full-thickness
      wounds.
AB  - BACKGROUND: Skin substitutes may be used as part of the management of acute
      surgical wounds. The ideal skin substitute should be biocompatible, inexpensive,
      free of potential pathogens, easy to store, prepare, and utilize. OBJECTIVE: To
      discuss the authors' direct clinical experience with an acellular, fetal bovine
      dermal matrix for the treatment of Mohs micrographic surgery (MMS) wound
      management. METHODS: After the cutaneous malignancies were cleared by MMS, a
      sheet of the product was prepared according to the manufacturer's instructions,
      trimmed to fit the defect, and then secured to the wound to enhance contact with
      the wound bed. RESULTS: Between June 2006 and July 2007, the product was used on
      a total of 10 wounds in 7 patients. Comorbidities included organ transplantation,
      Sezary syndrome with hepatitis C, and graft-versus-host disease. Seventy percent
      of the lesions were located on the lower extremities. The average defect area was
      13.4 cm2 (range: 4.0-32.0 cm2). The dermal substitute was fully incorporated in
      80% of defects and those that did not fully incorporate had exposed bone and
      tendon without the periosteum and peritendon, respectively. CONCLUSION: Skin
      substitutes may provide temporary coverage of acute, full-thickness surgical
      wounds allowed to heal by second intent. They may facilitate wound management
      with acceptable aesthetic outcomes. Alternate reconstructive options, however,
      such as cutaneous flaps, should be considered when there is exposed bone and/or
      tendon without their periosteum and/or peritendon.

PMID- 18720697
TI  - Nevus lipomatosus cutaneous superficialis of the groin arising in the fifth
      decade of life.
AB  - Nevus lipomatosus cutaneous superficialis (NLCS) is a rare malformation
      characterized by ectopic adipose tissue in the dermis. The lesion is usually
      present from birth or noticed in the first 2 decades of life. It occurs as
      sessile or pedunculated, domed nodular growths with a smooth, wrinkled, or
      cerebriform surface. Multiple lesions have a marked predilection for the gluteal
      region, lower back, and upper thigh, though solitary lesions may occur at unusual
      sites like the scalp, clitoris, and calf. An unusal case of NLCS is presented
      here where the solitary lesion occurred as a large exophytic growth arising at
      the groin in the fifth decade of life.

PMID- 18720698
TI  - Successful treatment of metastatic Crohn's disease with cyclosporine.
AB  - Metastatic Crohn's disease refers to cutaneous granulomatous lesions that are
      noncontiguous to the gastrointestinal tract. The treatment of cutaneous Crohn's
      disease is challenging. A patient with metastatic Crohn's disease whose lesions
      cleared after a 3-month course of cyclosporine is reported.

PMID- 18720699
TI  - Reticulated phototoxic eruption in a patient on long-term diltiazem therapy.
AB  - Diltiazem hydrochloride is a commonly prescribed medication in the treatment of
      cardiovascular disease. A case of diltiazem-induced hyperpigmentation in a
      patient after significant sun exposure is reported. The morphological appearance
      was reticulated and slate-gray to blue in color. The pathogenesis of the
      hyperpigmentation is discussed and possible treatment options are reviewed.

PMID- 18720700
TI  - Moxifloxacin as the likely cause of drug-induced linear immunoglobulin A bullous
      dermatosis.
AB  - Linear immunoglobulin A bullous dermatosis (LABD) is an immune-mediated
      subepidermal blistering disease that can be triggered by drug exposures, most
      notably, vancomycin. The authors report of a case of a 72-year-old man who
      developed LABD after a course of moxifloxacin. To the authors' knowledge, there
      is no other case of LABD caused by moxifloxacin in the medical literature.

PMID- 18720701
TI  - Development of systemic lupus erythematosus in a patient with rheumatoid
      arthritis following treatment conversion of infliximab to adalimumab.
AB  - Systemic lupus erythematosus (SLE)-like syndromes and the development of lupus
      related autoantibodies are known to occur during treatment with certain
      medications. Here a case of complete SLE conversion in a patient with rheumatoid
      arthritis following sequential treatment with infliximab and adalimumab is
      reported. Potential mechanisms for development of SLE with this treatment regimen
      are discussed, as well as the need for further exploration into autoimmune
      phenomenon with the use of immunobiologic agents.

PMID- 18720703
TI  - [Past, present and future of jaundice syndrome].

PMID- 18720702
TI  - Treatments for genital warts.

PMID- 18720704
TI  - [Gastroesophageal reflux disease: disputable and undecided questions (in memory
      of A. L. Grebnev)].

PMID- 18720706
TI  - [Central arterial pressure and importance of its examinations in pulmonology].
AB  - Arterial pressure (AP) measured on brachial artery now cannot be considered as an
      unique marker of vascular tonus. According to literature data, more informative
      and prognostically valued parameters are central AP (CAP) and indices of arterial
      rigidity, which closer bound with hypertrophy of vascular wall, intensity of
      vascular atherosclerotic lesion and occurrence of cardiovascular complications,
      than peripheral AP and some other classic risk factors. Nevertheless, CAP
      measuring cannot be considered as alternative to classic method of AP measuring
      on brachial artery; it only supplements our view of concrete pathological
      process. Non-invasive CAP measuring at diseases of respiratory organs can be
      usable for more precise assessment of cardiovascular risk at chronic and acute
      forms of diseases of pulmonary organs (DPO). The highest risk of CAP increase and
      cardiovascular complications take place in patients with chronic obstructive
      pulmonary disease (COPD), aggravation of severe bronchial asthma and in
      hypertensive patients with pneumonia or aggravation of chronic DPO. Results of
      CAP measuring can be used as additional diagnostic criteria of stratification of
      DPO and their complications risk. Early diagnostics of CAP disturbances (aortal
      hyper- o hypotension) make possible to correct therapy and prevent unfavorable
      consequences of hemodynamic disturbances. Dynamic control of CAP is reasonable to
      use for correction of therapeutic programs in departments of intensive care.

PMID- 18720705
TI  - [Pseudoinfectious endocarditis].
AB  - Nonbacterial thrombotic (noninfectious, pseudoinfectious--PIE) endocarditis is
      characterized by precipitation of thrombus, not containing bacteria, on the valve
      cusps. Mitral and aortal valves are affected most frequently. Vegetations, as a
      rule, do not exceed 6-7 mm and have a high inclination to embolism.
      Hypercoagulation plays a leading role in PIE pathogenesis. The most frequent
      acquired causes of sterile vegetation forming are malignant tumors and rheumatic
      diseases (especially systemic lupus erythematosus--SLE and antiphospholipid
      syndrome--APS). Valve pathology is most frequent lesion of heart in APS patients.
      It is supposed, that antibodies to phospholipids (aPL) have a special importance
      in valve lesion pathogenesis at APS, besides, changes in valve apparatus at SLE
      are associated exactly with aPL. Main problems of PIE patients are recurrent
      thromboembolism, development of valve dysfunction with clinical signs of heart
      failure (4-6% cases), difficulties in differential diagnostics: PIE is hard to
      diagnose if basic disease is accompanied by fever (diffuse diseases of connective
      tissue etc.). Transesophageal echocardiography is a leading method in PIE
      diagnostics. The main therapeutic option in PIE treatment is anticoagulant
      therapy: nonfractional or subcutaneous heparin in presence of systemic or
      pulmonary embolism, in patients with disseminated malignant tumors--complete
      doses of nonfractional heparin.

PMID- 18720707
TI  - [Pancreatitis in pregnant women].
AB  - Regardless of the fact, that pancreatitis during pregnancy is rare; this disease
      is characterized by high indices of maternal and perinatal mortality. Among
      variety of etiological and pathogenetic aspects of pregnant women's acute
      pancreatitis, leading role in its development belongs to bile-excreting system
      diseases, conditioned by physiological processes in women's organism during
      gestational period. Also there is a genetic theory of acute pancreatitis genesis
      in pregnant women, based on dislipoproteinemia development caused by lipoprotein
      lipase insufficiency, when severity of pancreatitis course is correlated with
      morphotype of this enzyme gene mutation. Chronic pancreatitis is conditioned by
      the same causes and can develop and recur during pregnancy and right after
      parturition. Diagnostics of pregnant women's pancreatitis is complicated because
      of limitation of the use of some methods (radiation and endoscopic). Pancreatitis
      clinical course does not differ from the one in nonpregnant women and is
      manifested by pain abdominal and dyspeptic syndromes, and also by syndromes of
      exocrine and endocrine pancreatic insufficiency. The main clinical feature of
      pregnant women's pancreatitis is high occurrence of painless forms. Approaches to
      treatment include pain relief disintoxication, use of pancreatic secretion
      blockers, multienzyme complexes, glycemia correction.

PMID- 18720708
TI  - [Metabolic syndrome: more questions than answers].
AB  - Metabolic syndrome has a close association with "diseases of civilization" and
      widespread in economically developed countries. By the end of XX century,
      unification in clusters of cardiovascular diseases risk factors showed, that
      simultaneous presence of obesity, type 2 diabetes mellitus, arterial
      hypertension, insulin resistance, hyperinsulinemia and hyperlipidemia contributed
      to significant increase in mortality.

PMID- 18720709
TI  - [Clinical features of chronic obstructive pulmonary disease course in persons who
      underwent radiation impact].
AB  - Experience of 10-years observation of 164 patients who underwent radiation
      impact, 38 (23%) afterwards had chronic obstructive pulmonary disease (COPD), is
      analyzed in the article. It is demonstrated, that timely COPD diagnostics must be
      based on thorough gathering of anamnestic data, analysis of clinical
      manifestations and results of annual examination of pulmonary ventilation
      function. Changes in time of COPD clinical symptoms among COPD patients who
      underwent radiation influence are considered. It was established, that in
      patients who underwent radiation influence, COPD began in younger age, coursed
      more severe, with more frequent aggravations, requiring inpatient treatment.
      Therapy of this category of persons required all drugs used at COPD treatment.

PMID- 18720710
TI  - [Clinicopathogenetic features of coronary heart disease combined with chronic
      obstructive pulmonary diseases and efficiency of therapy with trimetazidin].
AB  - Based on retrospective analysis of 2446 in-patient cards, autopsy protocols,
      outpatient medical documentation, prevalence and features of clinical
      manifestation of cardiorespiratory pathology (CRP): coronary heart disease (CHD)
      combined with chronic obstructive pulmonary disease (COPD)--1 stage of study, and
      also (after randomization and forming of main and control groups), efficiency of
      myocardial cytoprotector trimetazidin (TMZ) at its long-term use (1 year) in
      combined therapy (2 stage of study): 135 CHD patients (stable exertional angina
      functional class II-III: 92 and 43 persons respectively) with COPD of medium
      severe (111 persons) and severe course (24 persons), were studied. It is shown
      that CRP is prevailed in elder age groups (after 45 years) and noticed in 56.7%
      CHD patients. More sevenre course with great risk of myocardial infarction with Q
      wave (twice, p < 0.001), prolongation of painless ischemia (62.4+/-11.5 min/day
      vs. 22.8+/-11.1 min/day), inclination to complicated rhythm disturbances (38 vs.
      21.9, p < 0.05) and earlier clinical manifestations of heart failure (4.3+/-0.6
      years earlier, p < 0.001) is typical for CHD with COPD vs. patients without
      pulmonary pathology. In one year after beginning of treatment with TMZ (35 mg)
      number of weekly pain attacks was decreased in patients of 1st group vs. 2nd
      group (at the average -50.8% -29.3% vs. +12.5% +16.6% respectively); significant
      (p < 0.05) decrease in duration of painless myocardial ischemia was registered.
      Decrease in number of supraventricular and ventricular extrasystoles (42.7+/-1.48
      vs. 20.5+/-1.07 cases in a day, a < 0.0001), significant (p < 0.05) increase in
      ejection fraction and decrease in left ventricle end-diastolic volume (12.2+/
      0.4% E 12.2+/-0.3% respectively), in dimensions of left (10.9+/-0.03%) and right
      (8.8+/-0.9%) atrium, in risk of development of acute coronary syndrome were
      noticed in the patients of main group received TMZ. Thus, long-term (not less
      then 1 year) use of TMZ (35 mg) in combined treatment assists to normalization of
      cardiovascular indices, decreases cardiovascular complication occurrence,
      improves disease prognosis and do not has negative side-effects.

PMID- 18720711
TI  - [Laser Doppler fluometry in assessment of endothelium state in patients with
      coronary heart disease and its correction by intravenous laser irradiation of
      blood].
AB  - Influence of laser therapy on vascular endothelium function in patients with
      stable angina pectoris, detected by the method of laser Doppler fluorimetry, was
      studied. 77patients with stable angina pectoris were divided into 2 groups. In
      control group only medicamentous therapy was used, in main group a course of
      intravenous blood laser irradiation was carried out additionally. The increase of
      initially decreased mean index of microcirculation and index of microcirculation
      after acetylcholine iontophoresis was noticed. Tendency to increase of
      endothelial oscillations and capillary blood flow under influence of intravenous
      blood laser irradiation was noticed too. Laser therapy can be considered an
      effective method of increase of endothelial functional activity in patients with
      stable angina pectoris.

PMID- 18720712
TI  - [Indications and optimal terms of liver transplantation in chronic diffuse
      hepatic disease].
AB  - Patients with chronic diffuse hepatic disease (CDHD) take a great part in
      structure of morbidity of adult population. Problem of treatment of patients with
      hepatic cirrhosis (HC) is still very important. Main contingent of these patients
      who need hepar transplantation consists from HC patients with various ethiology,
      cholestatic diseases, inborn metabolism disturbances and hepatic tumors. At
      present in the world there is a tendency to early performing of operation while
      decompensation of other organs and systems still do not exist. When there is
      diagnosis of inborn metabolism disturbance indication to ortotopic
      transplantation of hepar (OTH) are put at the same time with verification of
      diagnosis. In case of HC urgency of OTH depends on stage of disease (system
      assessment of severity of hepatic insufficiency by 'hild-Pugh, MELD), response of
      patients on therapy and frequency of hospitalizing. Performance of OTH makes
      possible to prolongate of patients' life and significantly improve its quality.

PMID- 18720714
TI  - [Some proteins of acute phase of inflammation in differential diagnostics of
      rheumatoid arthritis].
AB  - Levels of lactoferrin (LF), antithrombin-III (AT-III) and beta2-macroglobulin
      (MG) in blood of patients with rheumatoid arthritis (RA), reactive arthritis
      (ReA) and systemic lupus erythematosus (SLE) were examined for assessment their
      importance in differential diagnostics of the diseases. It was shown that on the
      average, LF and AT-III levels were increased at RA, while MG level was
      practically unchanged. At the same time LF level was stable high regardless of RA
      activity and duration degree, but its concentration was significantly increased
      also in ReA patients (33% patients). AT-III, on the contrary, depended on process
      activity and duration, was more specific to RA, than LF, but its sensitivity at
      RA was not enough high (from 25 to 44% patients with increased levels subject to
      disease duration and activity). Coefficient LFE/AT-III, obtained by
      multiplication of these proteins concentration, had the greatest diagnostic
      value. Its sensitivity at RA is on the average 85%, and specificity at
      differential diagnostics of RA--80% vs. ReA and 92% vs. SLE. We consider that
      coefficient LFbetaAT-III can be used as an additional criterion at differential
      diagnostics at RA early stages, while other specific antibodies cannot be
      detected yet.

PMID- 18720713
TI  - [Influence of antidepressant therapy on psychovegetative disorders in patients
      with chronic calculous cholecystitis in perioperative period].
AB  - The results of prospective study of the stage of vascular endothelium and
      neutrophil phagocytic activity (NPA) in patients with chronic calculous
      cholecystitis (CCC) in perioperative period, who had anxious depressive
      disturbances (ADD), were represented. 61 patients were examined 3 weeks before
      cholecystectomy (CE). Intensity of anxiety and depression, vegetative tonus,
      desquamated endotheliocytes (DE) in blood and phagocytosis degree were assessed.
      The patients were randomized into 2 groups. The patients of 1st group (n = 30)
      received antidepressant coaxil during perioperative period (6 weeks); 2nd group
      (the control) was composed of 31 patients and was treated without coaxil. In 1st
      group significant decrease in AAD and symptoms of vegetative dystonia (VD) in 3
      weeks after CE was detected; number of DE in blood was considerable reduces, and
      NPA was significantly increased vs. control group. Correlation analysis made
      possible to show that the higher AAD and VD intensity, the more frequently
      epithelium desquamation was detected, and percentage of phagocytes was reduced at
      increase in DE in blood. Use of balanced antidepressant coaxil in perioperative
      period in CCC patients makes possible to reduce occurrence and intensity of AAD
      and VD after operation, improve vascular endothelium state, increase NPA and
      adaptive reserves of organism.

PMID- 18720715
TI  - [Optimization of therapy in patients with hepatic cirrhosis and encephalopathy].
AB  - With the aim of optimization of therapy of hepatic cirrhosis with manifestations
      of system encephalopathy 45 patients were examined. The patients were divided
      into 2 groups: control group (20 patients who received traditional therapy) and
      observing group (25 patients who in addition to traditional therapy received
      cryoapheresis). Clinical symptoms, results of neuropsychological and paraclinical
      examination, and indices of dynamic hepatobiliscintigraphy against the background
      of various methods of therapy were studied. It was established that with the use
      of pathogenetic therapy of hepatic encephalopathy--cryoapheresis--processes of
      hepatic encephalopathy progressing significantly decelerated, which made possible
      to approach to the choice of therapy individually, and, thereby, to optimize
      treatment.

PMID- 18720716
TI  - [Enteral nutrition as a method of correction of protein energetic insufficiency
      in patients with perforating gastric and duodenal ulcer].
AB  - The results of examinations and treatment of 338 patients operated by reason of
      perforated gastric and duodenal ulcer (PGDU). It was established, that parenteral
      and oral nutrition in PGDU patients after traditional surgical operation did not
      improve patients' trophic state. Performance of early enteral nutrition with
      Pevzner's diet and nutritive maintenance during all postoperative period in
      patients, operated by low-invasive methods, has favorable influence on patients'
      trophic state.

PMID- 18720717
TI  - [Case of giant cell myocarditis].
AB  - A case of giant cell myocarditis with atrioventricular blockade and progressive
      cardiac insufficiency is reported that required implantation of an artificial
      pacemaker and ended in the death of the patient. The diagnosis was confirmed by a
      histological study following autopsy. The difficulty of diagnosis of this rare
      form of myocarditis with an aggressive clinical course is emphasized. It is
      concluded that life-time endomyocardial biopsy, combined immunosuppressive
      therapy, and frequently heart transplantation taken together may prolong life
      expectancy in such patients.

PMID- 18720718
TI  - [General medical aspects of diagnostics quality].

PMID- 18720719
TI  - [Characteristics of a vasomotor endothelial function of the major and cerebral
      arteries in bronchial asthma].
AB  - We investigated endothelium dependent and independent activity of major and
      cerebral arteries in mice with experimental bronchial asthma. Regional features
      of endothelium dependent reactions of arteries were established. It was found
      that the carotid artery has greater vasomotor activity than the medial cerebral
      artery. Development of experimental bronchial asthma is associated with sharp
      reduction of reserve ability for endothelium independent dilatation against
      intensification of endothelium dependent dilatation; enhancement of constrictor
      effects of vascular endothelium in major and attenuation in cerebral
      compartments.

PMID- 18720720
TI  - [Effects of neuropeptides on interferon production in vitro].
AB  - The study of an interferon-inducing action of neuropeptides (a cerebrolysin
      model) on production of interferons by human blood leukocytes has shown that
      neuropeptides induce gamma-interferon production in the titer 267 IU/ml that
      determines one of the mechanisms of a neuroimmunocorrecting effect of
      cerebrolysin (Ebewe, Austria) in many neurological diseases (acute stroke, brain
      traumas and different neuroinfectious diseases).

PMID- 18720721
TI  - [Pathogenesis of ophthalmoherpes basing on the analysis of enzymes of the eye
      tissue and fluids].
AB  - To specify mechanisms of pathology development, we studied the activity of
      lysosomal glycosides in rabbit ocular tissues in experimental ophthalmoherpes.
      Rabbits with herpetic kepatitis show activation of beta-glucuronidase, beta
      glycosidase, alpha-mannosidase in cornial epithelium and stroma, iris, aqueous
      humor of herpes-infected and contralateral eye. The activity of the above three
      glycosidases in the tears of children with herpetic keratitis was enhanced. If
      their activity does not regress after the treatment, ophthalmoherpes recurrence
      may be expected in the near future. For realization of its genetic program herpes
      simplex virus in infected cells activates synthesis of acid glycosidases this
      leading to degradation of cornial cell membranes, virus spread in the tissues and
      release of lysosomal enzymes into tear fluid.

PMID- 18720722
TI  - [Adaptive mechanisms of circulatory systems in children with pulmonary
      hypertension syndrome in congenital valvular defect].
AB  - To evaluate the condition of the nitrogen oxide system and adaptation reserves in
      children with pulmonary hypertension syndrome and congenital heart disease, we
      examined 64 patients aged 3 to 17 years. The examination included standard
      cardiological tests, measurements of nitrogen oxide metabolites in blood, the
      activity of oxidant and antioxidant systems. Blood pressure in the right
      ventricle and pulmonary artery was controlled by invasive (catheterization of
      heart cavities, monitoring with Swan-Ganz catheter) and noninvasive (ultrasound)
      methods. We came to the conclusion that the level of nitrogen oxide is associated
      with the severity of pulmonary hypertension and characterizes the condition of
      the oxidant and antioxidant systems.

PMID- 18720723
TI  - [Characteristics of the hystiocyte reaction after ceolyte intake with food in
      ontogenesis in overheating and dry food eating].

PMID- 18720724
TI  - [A comparison of a cytokine status in pollenosis patients living in urban and
      rural areas].
AB  - Sixty patients with pollenosis were examined: 36 city inhabitants and 24
      villagers. The blood serum levels of IL-4, IFN-gamma and total IgE, production of
      IL-4, IFN-gamma by immunocompetent blood cells in vitro were determined. The
      correlation analysis detected more intensive involvement of IFN-gamma in allergic
      process in allergic patients living in the city. Estimation of spontaneous and
      induced cytokine production and their correlation (IS) showed that villagers had
      2.5 times higher IS of IFN-gamma cytokine.

PMID- 18720725
TI  - [Long-term results of treatment in patients with oligodendrogliomas and
      oligoastrocytomas of the cerebral hemispheres].
AB  - BACKGROUND: the current approach to treating patients with cerebral
      oligodendrogliomas and oligoastrocytomas involves surgical treatment with the
      maximum tumor resection in reasonable ranges, by taking into account the anatomic
      and physiological availability, followed by chemo- and radiotherapy.
      Nevertheless, it should be recognized that criteria for choosing the optimum
      regiment for the treatment of these tumors have not conclusively established.
      MATERIALS: the long-term results of treatment were analyzed in 80 patients with
      oligoglial tumors (oligodendrogliomas and oligoastrocytomas in 31 and 49
      patients, respectively) treated at the A.L. Polenov Russian Institute of
      Neurosurgery in 1990 to 2004. The patients' mean age was 18.9 years. 38.5% of
      tumors were located in the frontal lobe. In 67 (83.75%) patients, Karnoffsky
      score was 70-90. Radiotherapy was used in the treatment of 71 patients and
      postoperative chemotherapy in 52 (87,5%) patients. RESULTS: After complex
      therapy, the mean survival was 80.6 months in patients with oligodendrogliomas,
      63.3 months in those with anaplastic oligoastrocytomas, and 42 months in those
      with anaplastic oligodendrogliomas.

PMID- 18720726
TI  - [Efficiency of neuroendoscopic operations in achieving shunt independency in
      hydrocephalus with liquor-shunting system dysfunction].
AB  - OBJECTIVE: to evaluate the efficiency of endoscopic treatments in achieving shunt
      independency in patients with hydrocephalus and shunt dysfunction. SUBJECTS AND
      METHODS: endoscopic treatment was performed in 28 patients (15 males and 13
      females) aged 7.0 +/- 1.2 years (0.5-24 years) with hydrocephalus and CSF shunt
      dysfunction. The interval between the first shunt implantation and endoscopic
      surgery (the time of shunt dependency) was 43.4 +/- 7.8 months (5-180 months).
      All operations were made using the universal Gaab neuroendoscopic system (Karl
      Storz GmbH and Co., Germany). The follow-up lasted 49.4 +/- 6.9 months (6-120
      months). RESULTS: All the patients were successfully operated on, without
      intraoperative complications and deaths being observed. Surgical interventions
      were as follows: endoscopic ventriculocisternostomy (n=23), endoscopic
      aqueductoplasty (n=1), and endoscopic cystoventriculocistemrnostomy (n=4). In 24
      of the 28 patients, the symptoms of intracranial hypertension regressed
      completely. CSF shunt reimplantation was required in 3 cases and prolonged
      external drainage in 1 case of existing ventriculitis. It should be noted that 24
      of the 28 patients became shunt-independent; a shunt was removed in 13.

PMID- 18720727
TI  - [Neuromodulation--controlled analgesia. Criteria for long efficiency].
AB  - In the past three decades, there have been cardinal changes in the surgical
      treatment of chronic pain syndromes. The early used destructive methods have been
      mostly substituted for surgical neuromodulation techniques. These include: (1)
      neurostimulation--the electric stimulation (ES) of peripheral nerves, the spinal
      cord, and brain; (2) intrathecal drug delivery by means of programmed pumps.
      Neurostimulation techniques are more frequently used in the treatment of no
      cancer pain syndromes. Neurostimulation techniques are more frequently used in
      the treatment of no-cancer pain syndromes. Detailed analysis of our results
      showed that negative results and all cases with negative changes in follow-up
      were noted chiefly in patients with obvious and serious deafferentation signs.
      Testing ES is a major predictor of effectiveness for MCS. Positive results of
      chronic ES are observed in the vast majority of patients having good results in
      the postoperative testing period. Contrary to the current opinion as to worse
      follow-up results of chronic ES, we have seen positive changes in 5 patients
      followed up for about 3 years. Thus, by taking into account the high efficiency
      and minimal invasiveness of neurostimulation, no serious complications, as well
      as a possibility of improving the effectiveness of ES in a follow-up, this
      technique may be used as one of the first stages of surgical treatment of
      patients with neurogenic pain syndrome.

PMID- 18720728
TI  - [Correlation between the number of neurons and glial cells in neuronal formations
      of the brain in healthy humans].
AB  - The paper shows a relationship between the density of neurons and glia in the
      human gray matter in health and reveals an early unknown regularity in the ratio
      of the number of neurons and the density of glia in the human cerebral neuronal
      formations.

PMID- 18720730
TI  - [Cognitive disorders in patients after surgical treatment of intracranial
      arterial aneurysms].
AB  - In the review of the literature the authors analyze the problem of
      neuropsychological disorders in patients after subarachnoid hemorrhage,
      particularly that caused by arterial aneurysm rupture. Currently available data
      on the epidemiology, clinical characteristics, and risk factors of cognitive
      disorders in patients operated on for intracranial aneurysm rupture are
      presented. Treatment strategies and timing of surgery are analyzed. The basic
      trends in evaluation and treatment of neuropsychological disorders in patients
      with subarachnoid hemorrhage are noted.

PMID- 18720729
TI  - [Microsurgical anterior cervical foraminotomy in spondylogenous cervical
      radiculopathy].
AB  - The authors present the results of microsurgical anterior cervical foraminotomy
      used in unilateral cervical radiculopathy caused by lateral disc herniation or
      foraminal stenosis. In 2000 to 2006, anterior cervical foraminotomy was performed
      at one or two adjacent levels in 44 patients (27 males and 17 females aged 18 to
      64 years (mean age 43 years)) with cervical radiculopathy and myelopathy. All the
      patients underwent pre- and postoperative computed tomography, magnetic resonance
      imaging, and functional X-ray study. The surgical technique permitted anterior
      decompression of the affected nerve root from the site of its formation to the
      vertebral artery, by maintaining the stability and mobility of the involved
      vertebral segments. The immediate postoperative period was marked by excellent
      results with regression of radicular syndrome in 84% of the patients and by good
      results in 16%. A late (6-month-to-6-year) follow-up showed excellent (78%) and
      good (22%) results without additional surgery. The findings indicate that
      anterior cervical foraminotomy is an effective technique of nerve root
      decompression in patients with lateral disc herniation or foraminal stenosis.

PMID- 18720731
TI  - [Brain revascularization: history and state-of-the-art].

PMID- 18720732
TI  - [Effect of bacteriophage on the serum level of iron and copper in pregnant women
      with pyelonephritis].
AB  - Eighty-nine pregnant women, including 62 pregnant females with pyelonephritis,
      were examined. After bacteriophage treatment for pyelonephritis, there was an
      increase in the content of iron, a decrease in the level of soluble transferrin
      receptor without iron therapy, suggesting iron redistribution in pregnant woman.
      The blood levels of copper, ceruloplasmin, and transferrin in pregnant women with
      pyelonephritis point to antioxidative defense activation in both healthy pregnant
      women and pregnant females with pyelonephritis. The serum concentration of
      ceruloplasmin is of importance for prognosis and evaluation of ceruloplasmin in
      pregnant women. The higher content of ceruloplasmin in pregnancy is indicative of
      the involvement of protective mechanisms from autoaggression.

PMID- 18720733
TI  - [Nitric oxide metabolites and their significance in pathogenesis of bronchial
      asthma].
AB  - To study the possible potential of nitric oxide (NO) in the processes of atopic
      inflammation, the authors evaluated the intensity of nitrosyling and oxidative
      stresses in the bronchoalvelar lavage fluid and expired air condensate of
      patients with bronchial asthma (BA). Chronic inflammation was shown to result in
      an increase in the processes of nitration and oxidation in worsening BA and to
      reliably correlate with airway NO-producing functions, by explaining the
      pathological effects of NO due to the formation of 3-nitrotyrosine and malonic
      dialdehyde with the existing imbalance in NO metabolism, by intensifying
      nitrosylating stress. In the authors' opinion, nitrosothiols that are required as
      a NO donor may be rapidly destroyed or virtually do not form so the peroxynitrite
      nitrosothiol ratio may predetermine the final effects of NO.

PMID- 18720734
TI  - [Diagnostic value of the prognostic inflammation index in patients with open long
      bone fractures].

PMID- 18720735
TI  - [Role of immunological factors in the diagnosis and prediction of intrauterine
      fetal infections].
AB  - Comparative analysis of the data of immunological examination of pregnant women
      with markers of genitourinary infections (GUI), by taking into account the
      etiological factor, has established unidirectional changes in the levels
      cytokines and neopterin (NP). At the same time, the level of NP in all the groups
      of examinees with GUI was higher than that of cytokines. The highest content of
      NP in blood and cervical canal mucus (CCM) was noted in pregnant women with GUI
      of viral etiology. The changes in NP levels in infections caused by various
      viruses were similar. The study of the levels of cytokines and NP in the
      peripheral blood and CCM samples yielded information on the functional activity
      of different types of immunocompetent cells, the magnitude of an inflammatory
      process, its transition to the systemic level, and on the prediction of infection
      development.

PMID- 18720736
TI  - [Automatization of microscopic blood smear analyses and quality control using
      reference virtual slides].
AB  - MEKOC microscopy complexes have a group of specialized automatic functions for
      medical analyses of biomaterials integrated with general virtual microscopy
      accessories. Such functions provide a way of making specialized reference virtual
      slides (RVS). The latter contain the results of virtual analysis or expert
      evidence of the automatic analysis results presented in the virtual slide. The
      use of RVS yields an open system with a step-by-step control of the quality of
      automatic operations. RVS as realistic preparation models are also used to train
      staff. The results of step-by-step trials of the MEKOC--2 are presented in the
      paper.

PMID- 18720737
TI  - [Platelet functional status in patients with gastric cancer at combined treatment
      stages].
AB  - Platelets are active cells that excrete various humoral factors that contribute
      to thrombogenesis and inflammation. The investigation was undertaken to study
      induced platelet aggregation in patients with gastric cancer at combined
      treatment stages and to evaluate the impact of intraoperative radiotherapy (IOR).
      The study covered patients with gastric cancer (GC). Group 1 included Stage III
      GC patients who had undergone elective radical surgery; Group 2 comprised Stage
      III GC patients who had radical surgery with a session of IOR; Group 3 consisted
      of Stage IV GC patients who had undergone palliative surgery or explorative
      laparotomy. Induced platelet aggregation were explored from the BIOLA
      aggregometer (Russia) readings before, 30 minutes, 1, 3, 5, 7, and 14 days after
      surgery. Adenosine phosphate, adrenaline, collagen were used as inducers. It is
      concluded that there is a need for postoperative laboratory control and
      correction of platelet activity. In GC patients operated on with IOR, platelet
      activity should be monitored for at least 2 weeks after surgery.

PMID- 18720738
TI  - [Isolation and identification of Actinomyces bovis bacteria in purulent
      infections of mixed etiology].

PMID- 18720739
TI  - [Sudden hearing loss--our experience in treatment with vasoactive therapy].
AB  - INTRODUCTION: A specific title "sudden hearing loss" refers to illness which is
      characterized by a sudden, rapid sensoneural hearing loss mostly in one ear
      without obvious causes, accompanied with dizziness, and without vestibular
      symptomatology. It is defined as a hearing loss for more than 30 dB on 3 or more
      successive frequencies which appear in 72 hours. OBJECTIVE: The main goal of our
      paper was to estimate success of implementation of vasoactive method in patients
      with sudden hearing loss of senso-neural type in different ranges in hospital
      conditions. METHOD: Our research covered 37 patients hospitalized because of a
      sudden hearing loss of sensoneural type in different ranges. Diagnosis, in all
      patients, was established by clinical ORL examination, audiology and vestibular
      examination. R including CT and MR, neurological, internist and laboratory
      examinations were used in order to exclude other aetiology. In monitored
      patients, we started treatment with vasoactive therapy, ampules of xanthinol
      nicotinate (one ampule of 2 ml, 300 mg) or ampules of pentoxiphylline (one ampule
      of 5 ml, 100 mg) in form of infusions with addition of vitamins with an everyday
      gradual increase of dosage up to 12 ampules of xanthinol nicotinate and up to 5
      ampules of pentoxiphylline. Then we started with an everyday decrease of dosage
      down to the first one. RESULTS: After the complete curing protocol, we found out
      that in patients with light and medium senso-neural damages of hearing sense (23
      or 62%), hearing recovery was complete. In patients with heavy damage of hearing
      (9 or 24%), partial success was evidenced. The most difficult cases, with
      complete hearing loss, heavy buzzing and vertiginous problem (5 or 14%) responded
      to therapy, so buzzing and vertiginous problems disappeared but hearing was not
      improved. CONCLUSION: Usage of vasoactive medicaments in hospital conditions in
      treatment of sudden hearing loss gives good results and it is the closest to
      aetiological therapy.

PMID- 18720740
TI  - [Clinical impact of platelet rich plasma in treatment of gingival recessions].
AB  - INTRODUCTION: Root coverage supported with complete regeneration of lost
      periodontal tissues represents the ultimate goal of gingival recession treatment.
      OBJECTIVE: This study was designed to evaluate clinical effectiveness of platelet
      rich plasma gel (PRP) with connective tissue graft (CTG) in the treatment of
      gingival recession. METHOD: 15 gingival recessions Miller class I or II were
      treated with CTG and PRP (group PRP). Connective tissue graft was harvested from
      the premolar region using trap door technique. After elevation of the flap, the
      regional bone and root surface were smeared with activated PRP gel. CTG was also
      irrigated with PRP gel before placement over the exposed root surface and local
      bone. Fixed CTG was covered with a coronally advanced flap. The same number of
      gingival recessions were treated with CTG in combination with the coronally
      advanced flap with no PRP gel (group TVT). Clinical recordings included recession
      depth (RD), probing depth (PD), clinical attachment level (CAL) and keratinized
      tissue width (KT) before and 1 year after mucogingival surgical treatment.
      RESULTS: Mean value of RD was significantly decreased from 4.93 +/- 0.86 mm to
      0.60 +/- 0.37 (p < 0.01) with CTG and PRP and from 4.76 +/- 0.74 mm to 0.63 +/-
      0.29 mm (p < 0.01) in CTG group. This difference was not statistically
      significant. Results of the keratinized tissue width showed significant increase
      from 0.88 +/- 0.30 mm presurgery to 3.78 +/- 0.49 mm (p < 0.01) six months after
      treatment in PRP group and from 0.90 +/- 0.34 mm to 3.15 +/- 0.41 in TVT group (p
      < 0.01). This difference was statistically significant (p > 0.05). No
      statistically significant differences were observed between treatment groups in
      CAL and PD. CONCLUSION: Clinical results validate both procedures as effective
      and highly predictable surgical techniques in solving gingival recession problem.
      Histological evaluation may confirm advantage of PRP use related to regeneration
      of periodontal tissues.

PMID- 18720741
TI  - [Influence of physical treatment on disease activity and health status of
      patients with chronic arthritis].
AB  - INTRODUCTION: This is an open uncontrolled study about effects of physical
      treatment on disease activity parameters of patients with rheumatoid arthritis
      and psoriatic arthritis. OBJECTIVE: The aim of the study was to establish if
      there was any improvement of disease activity parameters after four weeks of
      physical and spa treatment. METHOD: We compared morning stiffness, tender and
      swollen joint count, body pain level and Disease Activity Score 28 (DAS-28) in
      patients with rheumatoid and psoriatic arthritis, and assessed the effect of
      physical and spa treatment on those parameters. The research encompassed 109
      patients: 69 with rheumatoid arthritis (RA group) and 40 with psoriatic arthritis
      (PA group). They were from Norway, staying for four weeks in June-September 2003.
      The groups served as their own controls--"one group pre-test post test" study.
      Disease activity measurement was made twice: at the beginning and at the end of
      treatment. The therapeutic set consisted of mud applications, kinesitherapy,
      mineral water pool and electrotherapy. RESULTS: At the beginning there was no
      significant difference in observed disease activity parameters between patients
      with rheumatoid and psoriatic arthritis (p > 0.05). After four weeks of physical
      and spa treatment disease activity was significantly reduced in all observed
      parameters in both groups: morning stiffness (p < 0.001 RA + PA), tender joint
      count (p < 0.01 RA + PA), swollen joint count (p < 0.01 RA; p < 0.05 PA), body
      pain (p < 0.01 RA + PA) and DAS-28 score (p < 0.01 RA+PA). CONCLUSION: Physical
      and spa treatment, together with climatic factors in Igalo, lead to a significant
      reduction of disease activity parameters of patients suffering from rheumatoid
      arthritis and psoriatic arthritis.

PMID- 18720742
TI  - [Glucoregulation in normal weight schizophrenia patients treated by first
      generation antipsychotics].
AB  - INTRODUCTION: Schizophrenia patients are at greater risk of obesity, diabetes
      mellitus (DM), lipid abnormalities and cardiovascular disorders. The metabolic
      complications in patients are associated with several risk factors: family
      history of DM, lifestyle, smoking, dietary habits, physical inactivity, but also
      with antipsychotic medication. In literature, most publications have been focused
      on the effects of the second generation antipsychotics (SGA) on glucose
      metabolism. However, less attention has been paid to abnormality in
      glucoregulation, patients with schizophrenia treated with the first generation
      antipsychotics (FGA). OBJECTIVE: The present study evaluated glucose metabolism
      in normal weight schizophrenia patients treated with FGA. METHOD: The cross
      sectional study included 18 patients (FGA treated) and 20 healthy controls with
      neither group differences in sex distribution, age, nor in BMI. Inclusion
      criteria were normal BMI (20-25 kg/m2). The glucose levels, insulin levels and
      growth hormone levels during oral glucose tolerance test (OGTT) were measured.
      RESULTS: Fasting glucose and insulin levels did not differ significantly between
      groups. Groups differed in OGTT glucose and insulin peak and area under curve
      (AUC), level of significance p < 0.05 (patients vs. controls: glucose peak 8.3 +/
      0.4 vs. 6.9 +/- 0.5 mmol/l, glucose AUC 758 +/- 28 vs. 640 +/- 36 mU/l/120 min;
      insulin peak in patients 92.7 +/- 15.6 mU/l; insulin AUC 6060 +/- 1016 mU/l/120
      min, insulin peak in controls 47.9 +/- 6.5 mU/l; insulin AUC 2597 +/- 256
      mU/l/120 min). CONCLUSION: Patients with schizophrenia, although with normal body
      mass index, are at high risk of abnormal glucose regulation. Not only SGA
      increase the risk of impaired glucoregulation and metabolic syndrome, but this
      may also be due to FGA or schizophrenia per se.

PMID- 18720743
TI  - [Upper gastrointestinal bleeding--five-year experience from one centre].
AB  - INTRODUCTION: Acute upper gastrointestinal bleeding is the commonest emergency
      managed by gastroenterologists. OBJECTIVE: To assess the frequency of erosive
      gastropathy and duodenal ulcer as a cause of upper gastrointestinal (GI) bleeding
      as well as its relation to age, gender and known risk factors. METHOD: We
      conducted retrospective observational analysis of emergency endoscopy reports
      from the records of the Emergency Department of Clinic for Gastroenterology and
      Hepatology, Clinical Centre of Serbia, during the period from 2000 to 2005. Data
      consisted of patients'demographics, endoscopic findings and potential risk
      factors. RESULTS: During the period 2000-2005, three thousand nine hundred and
      fifty four emergency upper endoscopies were performed for acute bleeding. In one
      quarter of cases, acute gastric erosions were the actual cause of bleeding. One
      half of them were associated with excessive consumption of salicylates and
      NSAIDs. In most of the examined cases, bleeding stopped spontaneously, while 7.6%
      of the cases required endoscopic intervention. Duodenal ulcer was detected as a
      source of bleeding in 1320 (33.4%) patients and was significantly associated with
      a male gender (71.8%) and salicylate or NSAID abuse (59.1%) (chi2-test; p =
      0.007). CONCLUSION: Erosive gastropathy and duodenal ulcer represent a
      significant cause of upper gastrointestinal bleeding accounting for up to 60% of
      all cases that required emergency endoscopy during the 5-year period. Consumption
      of NSAIDs and salicylates was associated more frequently with bleeding from a
      duodenal ulcer than with erosive gastropathy leading to a conclusion that we must
      explore other causes of erosive gastropathy more thoroughly.

PMID- 18720744
TI  - [Elevated body mass index and fatty liver].
AB  - INTRODUCTION: Obesity and overweight, expressed by elevated Body Mass Index
      (BMI), result from excessive consumption of fatty food and carbohydrates above
      the body needs. The fat from the blood, through free fatty acids, is taken
      directly into the liver. OBJECTIVE: The aim of this study was to examine
      correlation among the accepted ultrasonography findings of the fatty liver and
      the normal ultrasonography findings and the elevated average level of BMI and
      those with normal BMI in examinees in one investigation. All was done aimed at
      proving that the BMI is one of the direct factors of the increased occurence of
      fatty liver. METHOD: The method of the investigation consisted of anthropometric
      measuring of height and weight on the basis of which there were established BMI
      values. Consequently, the examinees were divided in two groups: one with normal
      BMI (under 24.9 kg/m2) and the other with increased BMI (over 25 kg/m2). Fatty
      liver was diagnosed when the liver of the examinees was observed by
      ultrasonography. Thus there were given subgroups of the examinees, one with the
      findings of fatty liver and the second with a normal finding, without changes.
      After that, the obtained results were statistically analysed. RESULTS: It was
      found that the average level of BMI in the examinees was by two units higher in
      the subgroup with ultrasonography findings of fatty liver than the average value
      of BMI in the subgroup with the normal ultrasonography findings of the liver. The
      difference was tested by the Student's t-test and a significant difference was
      found. The difference in frequencies of the appearance of the finding of fatty
      liver in the subgroups was tested by chi2-test. A statistically significant
      difference was found in frequencies of the appearance of fatty liver in the
      subgroup with the increased value of BMI. CONCLUSION: The increased BMI, which is
      represented by overweight and obesity, is one of the direct risk factors which
      cause fatty liver, checked by the US findings. Fatty liver can later progress to
      nonalcoholic fatty liver disease (NAFLD).

PMID- 18720745
TI  - [Y chromosome microdeletions in infertile male candidates for
      microfertilization].
AB  - INTRODUCTION: Y chromosome microdeletions are the second most frequent genetic
      cause of male infertility after Klinefelter's syndrome. OBJECTIVE: The aim of the
      study was to determine the frequency ofY chromosome microdeletions in a group of
      infertile men with an idiophatic cause of infertility, candidates for
      microfertilization (Intra-cytoplasmic Sperm Injection--ICSI) in Serbia and to
      correlate genotype-phenotype in patients with Y chromosome microdeletions.
      METHOD: One hundred and sixty patients with low sperm count (less than 5 x 10(6)
      spermatozoa/ml) were enrolled in the study. Forty patients were excluded from the
      study: ten because they were diagnosed with cytogenetic abnormality and thirty
      patients were diagnosed with other known causes of infertility. The control group
      consisted of 150 men who fathered at least one child in the last two years.
      Genomic DNA was extracted from peripheral blood samples and two multiplex
      polymerase chain reactions (PCR) analyses were performed using specific primers
      to confirm the presence or absence of Y chromosome microdeletions. RESULTS:
      Microdeletions were detected in 12 of 120 (10%) cases, while no deletions were
      detected in the control group. Of total number of 12 deletions, nine were
      detected in AZFc region (75%), one in AZFa (8%), and two in AZFbc (17%).
      CONCLUSION: Testing for Y chromosome microdeletions should be considered as an
      important element in diagnosis and genetic counselling of infertile couples in
      Serbia. Decisions regarding the assisted reproduction should be made based on the
      detailed clinical, endocrinological and cytogenetic examinations, spermogram,
      presence or absence and type of AZF microdeletions and CFTR gene mutations.

PMID- 18720746
TI  - [Comparative analysis of gynaecological status of workers from textile and metal
      industry].
AB  - INTRODUCTION: Female workers in textile and metal industry are exposed to various
      physical and chemical hazards that can lead to the occurrence of gynaecological
      diseases. OBJECTIVE: The aim of this study was to estimate the frequency of
      gynaecological diseases among workers of textile and metal industries. METHOD:
      The investigation comprised 197 female workers, 148 from textile and 49 from
      metal industry, aged from 26 to 57 years. All subjects were hospitalized based on
      non-gynaecological diagnoses. Gynaecological diagnoses included: tumours of the
      genital organs and breasts, cervical ectopy and lacerations, inflammatory
      diseases, disturbances of static of genital organs, cysts, and irregularities of
      menstrual cycle. RESULTS: Textile workers were significantly younger than metal
      workers, but the groups were comparable according to total and exposure work
      time, qualifications and diagnosis on hospital admission. Gynaecological diseases
      were diagnosed among all investigated subjects. About 80% were diagnosed with
      tumours and inflammatory diseases. A highly statistically significant difference
      was observed among groups according to the presence of cervical ectopy and
      lacerations, which were more frequent among textile workers. CONCLUSION:
      Comparison of gynaecological status of workers revealed that, among textile
      workers, cervical ectopy and lacerations were more frequent than among workers in
      metal industry.

PMID- 18720747
TI  - [Epidemiological analysis of demographic characteristics and type of injuries in
      patients with multiple trauma with respect to conclusive treatment outcome].
AB  - INTRODUCTION: Multiple trauma is one of the leading causes of mortality and
      morbidity in the population of people under 45 years of age. The consequences of
      multiple trauma have huge epidemiological, social and economic significance.
      OBJECTIVE: The aim of the paper was to analyse the conclusive treatment outcome
      of multiply traumatized patients with respect to their sex, age, injury mechanism
      and type. METHOD: This retrospective study included 100 patients with multiple
      injuries (ISS > 16) treated in the Emergency Room of the Clinical Centre of
      Serbia in the course of 2004. Clinical, X-ray, laboratory and numerical
      presentation methods--scores (ISS and GCS) were used to show the injury severity.
      RESULTS: Most of the injured were males (80%), and the average age was 40 +/- 20
      (5-83). Out of the total number of patients who died, 23 (82%) were males, and 5
      (18%) were females. The average age of the patients with fatal outcomes was 48 +/
      21 (8-86). Traffic accidents were the leading cause of injury (59%). The median
      GCS was 10 +/- 3 (3-15). The average ISS was 30 (20-66) in the surviving
      patients, and 53 (27-77) in those who died. CONCLUSION: With respect to sex, in
      most cases multiple trauma affects males (p < 0.01), with the average age of
      about 40. With respect to injury mechanism, the main cause of the occurrence of
      multiple trauma is traffic accidents (p < 0.01). There is a statistically
      significant difference in the values of GCS and ISS relative to the definitive
      outcome (p < 0.01). Statistical data processing indicated that there was a
      statistically significant correlation between mortality and type of injury in a
      given organic system (p < 0.01), but that there was no statistically significant
      correlation between mortality and age.

PMID- 18720748
TI  - [Frequency of alcohol use among elementary school pupils at Belgrade Territory].
AB  - INTRODUCTION: Alcoholism is one of the most frequent modern diseases. These kinds
      of epidemiological studies have not been carried out in this country at a global
      level. OBJECTIVE: The aim of the study was to establish the spread of alcohol
      abuse among the young regarding the sex, and find the connection between the
      alcohol abuse and the consumption of drugs and cigarettes. METHODS: The study was
      carried out among the elementary school pupils of the seventh and eighth grade in
      the area of Belgrade from October 2003 to January 2004. Total of 457 pupils were
      involved; 229 (50.1%) were boys and 228 (49.9%) girls, aged 12-15 years, the
      average age being 13.4 years. The method used was the modified questionnaire
      European School Survey Project on Alcohol and Other Drugs, which the pupils
      filled in individually, voluntarily and anonymously. Chi2-test, Student's t-test,
      Mann-Whitney Logistic Regression Test were used in statistical processing of the
      data. RESULTS: Almost 70% of the examinees have tried alcohol. Most of the
      examinees had the first contact with alcohol at the age of 11. Half of our
      examinees got drunk at least once in their life and about one fifth more than 20
      times. The binge form of Consumption (five or more drinks in a row) was evident
      in a quarter of our examinees. Our examinees use alcohol together with other
      psychoactive substances, mostly marijuana. It was observed that certain types of
      behaviour, such as frequent going out in the evening, were directly related to
      the abuse of alcohol. CONCLUSION: Two thirds of the examinees have tried alcohol.
      The first contact with alcohol is shifted to an earlier age (11 years). New
      trends of alcohol abuse have been noticed, such as binge form of consumption and
      the connection of use with other psychoactive substances.

PMID- 18720749
TI  - [Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL)--three case reports from Serbia].
AB  - INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is a hereditary microangiopathy leading to
      recurrent strokes and vascular dementia in young and middle-aged patients. The
      diagnosis of CADASIL is based on typical clinical presentation and characteristic
      magnetic resonance imaging (MRI) changes, and has to be confirmed by biopsy of
      the sural nerve, muscle and skin, as well as by genetic analysis. Mutations
      within the Notch3 gene were identified as the underlying genetic defect in
      CADASIL. CASE OUTLINE: The clinical manifestations of the first presented patient
      with migraine from the age of thirteen, stroke without vascular risk factors and
      stepwise progression of vascular dementia comprising the typical clinical picture
      of CADASIL, were confirmed after seven years with pathological verification. The
      second presented case did not satisfy the clinical criteria for CADASIL. His
      stroke was considered to be related with vascular risk factors--diabetes mellitus
      and hypertension. The aetiological diagnosis was established only when his
      brother without vascular risk factors presented with similar clinical
      manifestations. CONCLUSION: Until the development of the new neuroimaging
      techniques like MRI, pathologic and genetic analysis, CADASIL was considered as a
      rare disorder. However, the increasing number of CADASIL families has been
      identified throughout the world showing that this entity is usually
      underdiagnosed. This article presents three patients from two Serbian families
      with clinical suspicion of CADASIL verified by pathologic examination.

PMID- 18720750
TI  - [Osteomyelitis of right frontal sinus anterior wall].
AB  - INTRODUCTION: The paper describes a very rare, isolated exocranial complication
      of the purulent frontal sinus inflammation. Frontal bone osteomyelitis occurs
      either in the course of an acute episode or during the exacerbation of a chronic
      disease. By distribution, it can be diffuse or circumscript. It is more common in
      younger males. CASE OUTLINE: The case described is one of a 43-year-old patient
      with purulent frontal sinusitis developing into osteomyelitis of the anterior
      wall of the right frontal sinus, accompanied by the exteriorisation of the
      process into the frontal region soft tissues. The classical paranasal sinus
      radiography did not find any pathological changes in bony structures.
      Computerised tomography findings pointed to purulent inflammation of the frontal
      and part of the ethmoid sinuses, with a defect of the anterior wall of the right
      frontal sinus. CONCLUSION: Surgical exploration established a defect in the
      anterior wall of the right frontal sinus, with an organised purulent collection,
      1.3 cm in diameter. During surgery, evacuation of the inflamed mucosa and
      obliteration of the right frontal sinus were performed. Having analysed the
      anamnestic data, radiography and laboratory results, and intraoperative findings,
      we were not able to conclude decisively whether it was a complication of acute or
      chronic inflammation.

PMID- 18720751
TI  - [Fibromyxoid sarcoma of the pancreas].
AB  - INTRODUCTION: Fibromyxoid sarcoma is a rare mesenchymal neoplasm, usually
      appearing in the soft tissue of the extremities, less frequently in the groin,
      trunk, neck, and upper extremities. Within the abdomen, the tumour is usually
      localised within the retroperitoneum. CASE OUTLINE: We present a 56-year-old
      woman in whom, during the routinely performed investigation for atacks of choking
      with lots of bronchial secretion, and arterial hypertension, an ultrasonographer
      found a tumour within the head of the pancreas 6 x 6 cm in diameter. At
      operation, a dark pink, lobulated soft tumour, surrounded by a tiny capsule,
      clearly different from the completely normal pancreatic tissue of the posterior
      side of the head of the pancreas, was easily and ideally excised. The
      postoperative recovery was stormy. She developed postoperative pancreatitis,
      temporary biliary and duodenal fistula, which all settled by conservative
      treatment. The histology of the 80 g weighing tumour showed a circumscribed
      fibromyxoid sarcoma of low malignancy. Immunohistochemistry showed diffuse
      vimentin and CD34 strong positivity, as well as focal anti-SMA and anti-EMA
      immunopositivity. Six months after surgery, she died with signs of
      cerebrovascular insult, asthmatic status, and recurrent suppurative abdominal
      fistula, probably related to the previous pancreatitis. Ultrasonography showed a
      possible liver secondary. The exact cause of death was not confirmed as the
      autopsy was refused by the family. CONCLUSION: Primary sarcomas of the pancreas
      are very rare, but should be considered in differential diagnosis of pancreatic
      neoplasms. To the best of our knowledge, there has been no previously described
      fibromyxoid sarcoma of the pancreas.

PMID- 18720753
TI  - [Incidental finding of malignant renal cystic tumour diagnosed sonographically].
AB  - INTRODUCTION: Malignant cystic renal tumour is a rare variant of renal
      malignancy. Cystic neoplasm results from haemorrhage, necrosis and colliquation
      of a solid tumour or tumour occurring within the wall of a cyst. That
      pathoanatomic substratum reflects characteristic sonographic features indicating
      its malignant nature. It is important to distinguish a simple cyst (not requiring
      surgery) from intracystic malignant lesion because it requires surgery. CASE
      OUTLINE: The authors present a 59-year-old woman with a sonographic finding of a
      simple cyst in the upper pole of the right kidney revealed during gynaecological
      ultrasonography. Immediately afterwards, the radiologist performed renal
      sonography and its finding was a cystic lesion suggestive of malignancy. Further
      evaluation by CT scan showed that the lesion was clearly malignant. After
      surgery, the histological finding verified cystic renal cancer. CONCLUSION:
      Ultrasonography may reveal a complex cyst and solid mass but requires an
      experienced sonographer. Contrast CT scan would be performed to examine the
      "suspicious" lesion because it clearly shows if a cystic lesion is benign or
      malignant.

PMID- 18720752
TI  - [Spondylitis of thoracic spine--case report].
AB  - INTRODUCTION: Spondylitis is a rare bone and joint infection. It is a disease
      with long clinical history. Often, it is difficult to recognise symptoms at a
      proper time, and, due to the complex clinical outcome of spondylitis, a clinician
      may think about other problems in the body. CASE OUTLINE: A case report of a 59
      year-old male patient with thoracic spine spondylitis is presented, formerly
      treated as pulmonary thromboembolism with pericarditis. Only after neurological
      disorder such as paraplegia and orthopaedic consultative examination, real
      diagnosis was established. After that, the patient was hospitalized and operated
      on. CONCLUSION: A therapeutic approach to spondylitis is based on surgery,
      antibiotic drugs and symptomatic therapy. Due to the frequent occurrence of
      neurologic disorders, therapy could be prolonged and uncertain.

PMID- 18720754
TI  - [Dementia and diabetes mellitus].
AB  - Dementia and Diabetes mellitus (DM) are major health problems nowadays. DM leads
      to a significant cognitive decline and increases the risk of dementia, mostly
      Alzheimer's Disease (AD) and vascular dementia (VaD) by 50-100% and 100-150%,
      respectively. Amyloid beta (Abeta), the main pathogenic factor in AD development,
      is eliminated by advanced glycation end products (AGEs) and degraded by insulin
      degrading enzyme (IDE) for which it competes with insulin. Insulin stimulates
      secretion of Abeta and promotes brain inflammation. DM I and II cause slowing
      down of mental speed, lowering of mental flexibility and DM II learning and
      memory disturbances. DM acts both directly by hyperglycaemia and
      hyperinsulinaemia and by the blood vessel changes. Hyperglycaemia changes synapse
      plasticity and leads to cognitive decline. AGEs disrupt the neuron function and
      bonding to Abeta increases its aggregability. Glycation of tau protein promotes
      production of neurofibrillary tangles (NFT), the main intracellular pathogenic
      factor in AD. AGE 2 in DM causes pathological angiogenesis and apoptosis of
      neurons. AGE receptor (RAGE) is also the specific Abeta receptor with which it
      produces reactive oxygen species that has, as a result, disruption of
      mitochondrial function and reduction of neuronal energy resources.
      Insulinoresistance is linked with the dysexecutive syndrome, and
      hyperinsulinaemia increases the risk of AD especially by enhancing
      phosphorylation oftau protein and formation of NFT. Application of insulin showed
      improvement of memory, behaviour and affect in AD patients. Good glycoregulation
      emerged as an important factor in dementia prevention, and a better insight in
      relations of DM and brain function will lead to new potential dementia therapies.

PMID- 18720755
TI  - [Aortic stenosis: from diagnosis to optimal treatment].
AB  - Aortic stenosis is the most frequent valvular heart disease. Aortic sclerosis is
      the first characteristic lesion of the cusps, which is considered today as the
      process similar to atherosclerosis. Progression of the disease is an active
      process leading to forming of bone matrix and heavily calcified stiff cusps by
      inflammatory cells and osteopontin. It is a chronic, progressive disease which
      can remain asymptomatic for a long time even in the presence of severe aortic
      stenosis. Proper physical examination remains an essential diagnostic tool in
      aortic stenosis. Recognition of characteristic systolic murmur draws attention
      and guides further diagnosis in the right direction. Doppler echocardiography is
      an ideal tool to confirm diagnosis. It is well known that exercise tests help in
      stratification risk of asymptomatic aortic stenosis. Serial measurements of brain
      natriuretic peptide during a follow-up period may help to identify the optimal
      time for surgery. Heart catheterization is mostly restricted to preoperative
      evaluation of coronary arteries rather than to evaluation of the valve lesion
      itself. Currently, there is no ideal medical treatment for slowing down the
      disease progression. The first results about the effect of ACE inhibitors and
      statins in aortic sclerosis and stenosis are encouraging, but there is still not
      enough evidence. Onset symptoms based on current ACC/AHA/ESC recommendations are
      I class indication for aortic valve replacement. Aortic valve can be replaced
      with a biological or prosthetic valve. There is a possibility of percutaneous
      aortic valve implantation and transapical operation for patients that are
      contraindicated for standard cardiac surgery.

PMID- 18720756
TI  - [Why carotid endarterectomy is method of choice in treatment of carotid
      stenosis].
AB  - Procedures used in treatment of carotid stenosis are endarterectomy, PTA with
      stent implantation, resection with graft interposition and by-pass procedure.
      Segmental lesions are found more often and treated by the first two mentioned
      procedures. In case of longer lesions and extension to the greater part of the
      common carotid artery, the other two procedures are performed. For the past few
      years, the main dilemma has been whether to perform carotid endarterectomy or PTA
      with stent implantation. Both early and long-term results speak in favour of
      carotid endarterectomy, regardless of an increased number of PTA and carotid
      stenting. At the same time, PTA and carotid stenting are more expensive
      procedures. Both methods have their defined and important roles in treatment of
      segmental occlusive carotid lesions. Severe cardiac, pulmonary and renal
      conditions, which increase the risk of general anaesthesia, are not an absolute
      indication for PTA and stenting, since endarterectomy can be done in regional
      anaesthesia. Main indications for PTA with stent implantation are: surgically
      inaccessible lesions (at or above C2; or subclavian); radiation-induced carotid
      stenosis; prior ipsilateral radical neck dissection; prior carotid endarterectomy
      (restenosis).

PMID- 18720757
TI  - Molecular mechanisms involved in chemoresistance in paediatric acute
      lymphoblastic leukaemia.
AB  - Acute lymphoblastic leukaemia (ALL) is the most common paediatric cancer. Despite
      cure rates approaching 80%, resistance to treatment and disease relapse remain a
      significant clinical problem. Identification of the genes and biological pathways
      responsible for chemoresistance is therefore crucial for the design of novel
      therapeutic approaches aiming to improve patient survival. Mutations in the
      membrane transporter P-glycoprotein genes, genetic variations in drug
      metabolising enzymes and defects in apoptotic pathways are mechanisms of
      chemoresistance common to a wide spectrum of cancers and also play a role in
      paediatric ALL. In addition, several recent microarray studies have identified
      transcriptional profiles specifically associated with chemoresistance and pointed
      to a number of potentially novel therapeutic targets. These microarray studies
      have shown that genes discriminating between clinically responsive and resistant
      leukaemias tend to be involved in cellular processes such as regulation of cell
      cycle, proliferation, and DNA repair. Here we review the outcomes of these
      microarray studies and also present our own investigations into apoptotic
      resistance to DNA double strand breaks (DSBs) in paediatric ALL. We present
      stratification of paediatric ALL by the profile of DNA damage response following
      ionising radiation (IR) in vitro. This approach allows classification of ALL
      tumours at presentation into IR-apoptotic sensitive and IR-apoptotic resistant.
      Furthermore, apoptotic resistant leukaemias exhibit abnormal response of NFkB
      pathway following irradiation and inhibition of this pathway can sensitise
      leukaemic cells to IR-induced DSBs.

PMID- 18720758
TI  - [Focused ultrasound for treatment of uterine myoma: from experimental model to
      clinical practice].
AB  - It is well known that focused ultrasound has a biologic effect on tissue. High
      intensity focused ultrasound (HIFU) on a small target area raises the temperature
      of the tissue enough to denaturate proteins and cause irreversible cell damage.
      The tight focus of the ultrasound energy allows delivery of the intended dose to
      a very precise location. The resulting coagulation necrosis is relatively
      painless. The application of this method in the human clinical setting has
      required pilot studies on an animal model. Although the treatment had a high
      success rate, there was a significant percentage of complications, mainly
      attributed to the technical drawbacks of the procedure. Therefore, this method
      has been modified for use in humans, and the HIFU is now guided, monitored and
      controlled by magnetic resonance imaging (MRI). In October 2004, Food and Drug
      Adiministration (FDA) approved MRI guided focused ultrasound treatment of uterine
      fibroids in humans. Since then, successful treatment of uterine myomas by HIFU
      has been performed in thousands of women.

PMID- 18720760
TI  - [Analysis of irregularities in writing English and Serbian professional papers].
AB  - There are many peculiarities and indecisions in the English and Serbian language.
      One of the crucial is doubtless a translation from Serbian into English. On the
      other hand, by analysing professional papers of English native speakers, a
      tendency of greater conciseness is shown. Thus a better knowledge of etymological
      structure and modern formal style in both languages is essential. Accordingly, it
      is of utmost importance to pay a special attention to appropriate collocations,
      text summarizing and various possible mistakes ranging from wrong spelling and
      improper use of some abbreviations of conventional titles to incorrect
      capitalization, hyphenated words, etc. Language is certainly a vivid unique style
      of each personality, even in professional formal writing, but, by using it, we
      naturally enrich the expression and quality of the language as a whole.

PMID- 18720759
TI  - [Buffon (1707-1788)].
AB  - The aim of this paper is to remember the great French naturalist Georges-Louis
      Leclerc, Count Buffon, as well as to point out his overall significance and work
      concerning medicine. Buffon's book The History of Nature, General and Particular,
      comprising 44 volumes, was the first systematized review of the contemporary
      knowledge of the history of nature, geology and anthropology, and the beginning
      of cosmology, palaeontology, ecology and numerous other sciences. The second
      volume is the most important for medicine discussing man. In its first part,
      Buffon presented the general knowledge concerning reproduction, nutrition, growth
      and development, then the formation and development of the foetus, while, in the
      second part, he discussed the nature of man including childhood, puberty,
      maturity (with an account of man), old age and death. Buffon made a valuable
      contribution to natural sciences and mathematics getting eternal glory as a
      naturalist, biologist, cosmologist and writer.

PMID- 18720761
TI  - Artifacts in digital radiography.
AB  - Digital radiography is becoming more prevalent in veterinary medicine, and with
      its increased use has come the recognition of a number of artifacts. Artifacts in
      digital radiography can decrease image quality and mask or mimic pathologic
      changes. They can be categorized according to the step during which they are
      created and include preexposure, exposure, postexposure, reading, and workstation
      artifacts. The recognition and understanding of artifacts in digital radiography
      facilitates their reduction and decreases misinterpretation. The purpose of this
      review is to name, describe the appearance, identify the cause, and provide
      methods of resolution of artifacts in digital radiography.

PMID- 18720762
TI  - Contrast-enhanced fluid-attenuated inversion recovery vs. contrast-enhanced spin
      echo T1-weighted brain imaging.
AB  - In humans, contrast-enhanced fluid-attenuated inversion recovery (FLAIR) imaging
      plays an important role in detecting brain disease. The aim of this study was to
      define the clinical utility of contrast-enhanced FLAIR imaging by comparing the
      results with those with contrast-enhanced spin echo T1-weighted images (SE T1WI)
      in animals with different brain disorders. Forty-one dogs and five cats with a
      clinical suspicion of brain disease and 30 normal animals (25 dogs and five cats)
      were evaluated using a 0.2 T permanent magnet. Before contrast medium injection,
      spin echo T1-weighted, SE T1WI, and FLAIR sequences were acquired in three
      planes. SE T1WI and FLAIR images were also acquired after gadolinium injection.
      Sensitivity in detecting the number, location, margin, and enhancement pattern
      and rate were evaluated. No lesions were found in a normal animal. In affected
      animals, 48 lesions in 34 patients were detected in contrast-enhanced SE T1WI
      whereas 81 lesions in 44 patients were detected in contrast-enhanced FLAIR
      images. There was no difference in the characteristics of the margins or
      enhancement pattern of the detected lesions. The objective enhancement rate, the
      mean value between lesion-to-white matter ratio and lesion-to-gray matter ratio,
      although representing an overlap of T1 and T2 effects and not pure contrast
      medium shortening of T1 relaxation, was better in contrast-enhanced FLAIR images.
      These results suggest a superiority of contrast-enhanced FLAIR images as compared
      with contrast-enhanced SE T1WI in detecting enhancing brain lesions.

PMID- 18720763
TI  - Magnetic resonance imaging features of empty sella in dogs.
AB  - In humans, the empty sella is defined as herniation of the subarachnoidal space
      into the sella turcica with invisible (total empty sella) or reduced (partial
      empty sella) hypophyseal size. An empty sella can be associated with endocrine
      disturbances. The purpose of this study was to determine if the empty sella
      exists in dogs or cats and whether it is associated with endocrinopathy or
      hydrocephalus. Archived magnetic resonance images of the head of 370 dogs and 77
      cats were re-evaluated specifically for the presence or absence of the pituitary
      gland. Hypophyseal tissue filling more than 50% of the sella was considered
      normal, between 30% and 50% was defined as partial empty sella and less than 30%
      was defined as total empty sella. In patients with an empty sella, and in all
      other imaged dogs of the affected breeds, the ventricle to brain ratio was
      measured. In patients with an empty sella, the medical record was searched for
      evidence of endocrinopathy. No cat had an empty sella but 11 dogs (3%) had a
      small or missing hypophysis. Seven of these dogs had a ventricle to brain ratio
      greater than 15%. Only small dogs (mean weight of 6.7kg) were affected. One dog
      with an empty sella had signs of central hyperadrenocorticism while the other 10
      had no sign of endocrinopathy. We conclude that the empty sella exists in dogs
      but is not generally associated with endocrinopathy.

PMID- 18720764
TI  - Magnetic resonance imaging of feline hippocampal necrosis.
AB  - The clinical, neuropathologic, and magnetic resonance (MR) imaging features in
      four cats with necrosis of the hippocampus and piriform lobe are described. All
      cats had acute generalized seizures and behavioral changes including aggression,
      salivation, polyphagia, and disorientation. Routine hematologic, serum chemistry,
      and cerebrospinal fluid analyses were normal. MR imaging abnormalities were
      restricted to the area of the hippocampus and piriform lobe. The lesions were T2
      hyperintense, T1-hypointense, and were characterized by various degrees of
      contrast enhancement. Lesions were consistent with necrotizing encephalitis. Two
      cats were euthanized and underwent postmortem examination within a week after MR
      imaging due to the lack of response to antiepileptic drug therapy and progressive
      encephalopathy [corrected] The remaining two cats lived for about four months and
      were then euthanized because of persistent behavioral and neurologic signs; only
      one of these cats underwent postmortem examination with histopathologic
      examination. Histopathological findings were typical of severe, diffuse,
      bilateral symmetric necrosis, and degeneration of neurons in the hippocampus and
      piriform lobe, but an etiologic agent was not apparent. This apparently unique
      feline syndrome, now reported in Switzerland and Italy, has no known cause at
      this time.

PMID- 18720765
TI  - Characterization of normal feline renal vascular anatomy with dual-phase CT
      angiography.
AB  - Helical computed tomography angiography was used to evaluate the renal vascular
      anatomy of potential feline renal donors. One hundred and fourteen computed
      tomography angiograms were reviewed. The vessels were characterized as single
      without bifurcation, single with bifurcation, double, or triple. Multiplicity was
      most commonly seen for the right renal vein (45/114 vs. 3/114 multiple left renal
      veins, 0/114 multiple right renal arteries, and 8/114 multiple left renal
      arteries). The right kidney was 13.3 times more likely than the left to have
      multiple renal veins. Additional vascular variants included double caudal vena
      cava and an accessory renal artery. For the left kidney, surgery and computed
      tomography angiography findings were in agreement in 92% of 74 cats. For the
      right kidney, surgery and computed tomography angiography findings were in
      agreement in 6/6 cats. Our findings of renal vascular anatomy variations in cats
      were similar to previous reports in humans. Identifying and recognizing the
      pattern of distribution of these vessels is important when performing renal
      transplantation.

PMID- 18720766
TI  - Imaging diagnosis--congenital structural hyoid bone abnormalities in a dog.

PMID- 18720767
TI  - Imaging diagnosis--laryngeal collapse due to cricoid cartilage fracture.

PMID- 18720768
TI  - Imaging diagnosis--trauma-induced tension pneumocephalus.

PMID- 18720769
TI  - Imaging diagnosis--intra-abdominal necrotic lipoma.

PMID- 18720770
TI  - Qualitative and quantitative comparison of renal vs. hepatic ultrasonographic
      intensity in healthy dogs.
AB  - A prospective, cross-sectional study was performed to qualitatively and
      quantitatively compare the echogenicity of the renal cortex relative to the liver
      in healthy dogs. Twenty-five normal adult dogs were examined
      ultrasonographically. Three standard B-mode images (8.0 MHz) and three tissue
      harmonic images of the cranial pole of the right kidney adjacent to the caudate
      lobe of the liver were obtained. Renal and hepatic echogenicities were
      qualitatively compared by two observers. Subsequently, regions of interest (ROIs)
      were drawn in the renal cortex and the adjacent liver parenchyma at equal depths
      on each image, using two different ROI geometries: deep adjacent half-annular
      ROIs centered at the focal zone and small superficial adjacent squares placed in
      the near field. Renal and hepatic mean pixel intensities were quantified and
      averaged for individual subjects. Qualitatively, the right renal cortex was more
      commonly hyperechoic to liver. Quantitatively, the renal cortical mean pixel
      intensity was significantly higher than that of liver using deep half-annular
      ROIs, but not superficial square ROIs, for both standard (P = 0.0007) and
      harmonic (P = 0.0107) tissue imaging. These findings suggest that the renal
      cortex can be slightly hyperechoic to adjacent liver. The framework within which
      the canine renal cortical parenchyma is routinely evaluated in abdominal
      ultrasonography should be reconsidered, and mild hyperechogenicity relative to
      the liver (at 8.0 MHz) interpreted as a normal finding.

PMID- 18720771
TI  - Lung ring-down artifact as a sign of pulmonary alveolar-interstitial disease.
AB  - Three dogs with presumptive cardiogenic pulmonary edema underwent a thoracic
      ultrasonographic examination. Multiple ring-down artifacts involving both sides
      of the thorax emanating from the pleural-lung interface were detected. When
      clinical and radiographic signs of pulmonary edema were resolved, ring-down
      artifacts were not observed. The ring-down artifact may be a useful diagnostic
      sign for screening the lung of animals with acute respiratory distress where
      radiographs are not feasible.

PMID- 18720772
TI  - Ultrasonographic evaluation of normal canine iliopsoas muscle.
AB  - The aim of this study was to describe the normal ultrasonographic appearance of
      the iliopsoas muscle and related landmarks. Hind limbs of five dog cadavers with
      no history of lameness were evaluated. The origin and mid-body of the psoas major
      and the common insertion of the iliacus and psoas major on the lesser trochanter
      of the femur were identified and evaluated. New methylene blue was injected under
      ultrasonographic guidance at the three sites. Dissection was performed to confirm
      placement of the dye. The L3 origin, mid-body, and insertion of the muscle were
      identified in all dogs and were consistent in appearance and compatible with the
      general appearance of muscle and tendons. The L2 origin was consistently
      difficult to image. The same ultrasound technique was subsequently applied to
      four healthy dogs, and consistent images of the iliopsoas muscle and associated
      landmarks were obtained. In this study, the major structures of the iliopsoas
      could be identified and in all dogs had a similar appearance. Ultrasound is an
      important tool for the diagnosis of musculotendinous injury and may be useful for
      identification of ilipsoas injury as a cause of lameness in the dog.

PMID- 18720773
TI  - Evaluation of free radical formation associated with diagnostic ultrasound.
AB  - Our objective was to evaluate kidney antioxidant status in rats subjected to an
      ultrasound examination. Thirty rats were divided into five groups for injection
      of saline (S) or anesthetic (A), and application of ultrasound using different
      modes, B mode, pulsed wave Doppler, and continuous wave Doppler, under
      anesthesia. Ultrasound was performed on days 1, 3, and 5 relative to the
      initiation of the experiment. Rats were then scarified on day 6. The kidney
      tissue thiobarbituric acid reactive substance (TBARS) level and superoxide
      dismutase (SOD) activity were measured. Both TBARS level and SOD activity
      increased, 21% and 38%, respectively, due to anesthesia (P < 0.04 for both). SOD
      activity increased further by a factor of 1.2 in response to ultrasound
      examination (P < 0.05), whereas TBARS level was not affected by Doppler and
      continuous wave Doppler compared to anesthesia. Increases in the level of TBARS
      (P < 0.03) and SOD activity (P < 0.01) were greatest when B-mode ultrasound was
      employed. These substances did not increase further when continuous wave Doppler
      was employed. The peak-negative acoustic pressure (9.16 vs. 9.74 MPa) and
      frequency (3.57 vs. 6.95 MHz) for B mode and pulsed wave Doppler were greater
      than those for continuous wave Doppler (0.22 MPa and 1.96 MHz). The estimated
      mechanical indexes were 4.87, 3.70, and 0.15 for B mode, pulsed wave Doppler, and
      continuous wave Doppler, respectively. In conclusion, anesthesia may cause tissue
      damage as reflected by elevated lipid peroxidation and free radical formation and
      ultrasound examination may amplify tissue damage through mechanical effects
      caused by ultrasound absorption.

PMID- 18720774
TI  - Scintigraphic and radiographic evaluation of appendicular skeletal lesions in
      cold-stunned Kemp's ridley sea turtles.
AB  - Osteolytic appendicular skeletal lesions in eight-stranded, cold-stunned Kemp's
      ridley sea turtles (Lepidochelys kempii) were evaluated using radiography and
      skeletal scintigraphy. Radiographic studies were performed monthly in most
      animals. Follow-up scintigraphy was performed 45-120 days after the initial exams
      in six turtles. Radiographically, lesions slowly progressed from an early
      osteolytic process contained to either the proximal or distal end of long bones,
      to a later stage characterized by thickening of the affected bone, sclerosis, and
      remodeling of the lesion borders. In seven turtles, the initial scintigrams were
      characterized by at least one focus of abnormal radiopharmaceutical uptake that
      correlated with a lytic site noted in radiographs. In five turtles, scintigraphic
      lesions were characterized by asymmetric radiopharmaceutical uptake rather than
      by increased intensity of uptake. Scintigraphic studies obtained more than 4
      months after the appearance of clinical and radiographic signs had minimal, if
      any, abnormal radiopharmaceutical uptake, despite the persistence of abnormal
      radiographic findings. Skeletal scintigraphy is an effective method for more
      precisely determining if and when these animals can be returned to the wild.
      Animals were released if normal radiopharmaceutical uptake was seen during
      initial examination, or if decreased uptake was noted between serial
      examinations. In four of the turtles, resolution of abnormal scintigraphic
      findings permitted an objective decision to discontinue antibiotic and antifungal
      therapy. Seven of the eight turtles were released after correlation of the
      clinical signs with the imaging findings. Radiographs, however, are still needed
      to facilitate the correct identification of lesions with scintigraphy.

PMID- 18720775
TI  - Use of surgical hemoclips in radiation treatment planning.
AB  - The goal of this prospective study was to determine the effect of hemoclip use on
      the size of radiation treatment fields based on a 3-cm margin around a surgical
      incision alone (field setup 1) vs. a 3-cm margin around the surgical incision
      plus hemoclips (field setup 2). Forty-seven dogs that underwent surgical
      resection of a total of 55 soft tissue masses had surgical hemoclips placed at
      the time of surgery and orthogonal radiographs made immediately postoperatively.
      Radiation treatment field simulation was done and field areas measured.
      Additional determinations included number of hemoclips outside of the radiation
      treatment field based on a margin around the incision alone, hemoclip distance
      from the incision, and association between incision length and greatest distance
      of hemoclips from the incision. There was a significant difference in radiation
      treatment field size using information regarding the location of hemoclips in
      conjunction with the surgical scar compared with the surgical scar alone for
      truncal (P = 0.0003) vs. extremity tumors (P = 0.087). In simulating radiation
      treatment fields hemoclips were located outside of field setup 1 for the majority
      of tumors (79%) resected from the trunk but only in a minority of tumors (10.7%)
      resected from extremity sites. The findings from this study suggest that surgical
      hemoclips have potential utility in simulation of radiation treatment fields in
      the postoperative setting.

PMID- 18720776
TI  - Laparoscopically implanted tissue expander radiotherapy in canine transitional
      cell carcinoma.
AB  - Organ motion and injury to adjacent structures limit curative treatment of
      intraabdominal tumors with external beam radiotherapy. We evaluated the use of
      Laparoscopically Implanted Tissue Expander Radiotherapy (LITE-RT) to exclude
      critical structures during irradiation of the urinary bladder in two dogs with
      transitional cell carcinoma (TCC) using helical tomotherapy. Dogs had
      histologically confirmed bladder TCC with no metastasis. A custom-shaped tissue
      expander was placed between the colon and bladder laparoscopically in one dog and
      during laparotomy in the other. The prescribed radiation dose was 45 Gy to 98%
      volume of the bladder in 18 fractions of 2.5 Gy. Tumor response and normal tissue
      effects were monitored with cystoscopy and colonic biopsies before treatment and
      3, 6, and 15 months after treatment. Based on treatment plans from inflated vs.
      deflated tissue expander CT images, there was a mean dose reduction to the colon
      of 53% and 31% for the two dogs. Interfractional target repositioning was
      possible by using volumetric megavoltage computed tomography helical tomotherapy.
      Both dogs had no clinical signs of chronic colitis but did experience mild
      cystitis during treatment. Tissue expanders became detached, requiring an
      additional surgery for reattachment, in both dogs. One dog developed a fibrous
      adhesion resulting in bladder rupture during inflation, which necessitated early
      device removal. One dog was euthanized for tumor-associated ureteral obstruction
      at 8 months while the other is alive at 21 months. We conclude that LITE-RT shows
      promise in treatment of canine bladder TCC due to lack of acute colitis and
      enteritis.

PMID- 18720777
TI  - Statistical briefing: measurement scales.

PMID- 18720779
TI  - [Application of terahertz time domain spectroscopy to explosive and illegal
      drug].
AB  - Terahertz waves (THz, T-ray) lie between far-infrared and microwave in
      electromagnetic spectrum with frequency from 0.1 to 10 THz. Many explosives and
      illicit drugs show characteristic spectral features in the terahertz. Compared
      with conventional methods of detecting a variety of threats, such as weapons,
      explosives and illegal drugs, THz radiation is low frequency and non-ionizing,
      and does not give rise to safety concerns. Moreover, THz can penetrate many
      barrier materials, such as clothing and common packaging materials. THz technique
      has a great potential and advantage in antiterrorism and security inspection of
      explosives and illegal drugs due to the ability of high-sensitivity,
      nondestructive and stand-off inspection of many substances. The present paper
      summarizes the latest progress in the application of terahertz time domain
      spectroscopy (THz-TDS) to explosives and illegal drugs. Studies on RDX are
      discussed in details and many factors affecting experiments are also introduced.

PMID- 18720778
TI  - [THz absorption spectra of several carbohydrate derivatives].
AB  - Intermolecular hydrogen bond vibrations may be observed in the THz range.
      Carbohydrates are important bio-molecules, and are the typical systems for the
      study of hydrogen bonds. Carbohydrate derivatives have critical biological
      functions, and there are extensive hydrogen bond networks in molecular system,
      therefore, they would have various bands in the THz region. The THz absorption
      spectra of several carbohydrate derivatives were measured using a THz apparatus
      at room temperature. The THz bands are as follows: 1.17, 1.35, 1.93 and 2.23 THz
      for isopropyl-beta-D-thioglucopyranoside; 1.93 THz for isopropyl-beta-D-
      thiogalactopyranoside; 1.87 THz for methyl-(tetra-O-acetyl-beta-D
      galactopyranoside); 1.23, 1.70, 1.84 and 2. 23 THz for O-(2, 3, 4, 6-tetra-O
      acetyl-beta-glucopyranosyl)-N-hydroxysuccinimide. The results indicate that
      different samples have various bands that originated from collective modes of the
      whole molecules and especially isomers can be distinguished, showing that THz
      method is sensitive to the molecular structures and spatial configurations and is
      a helpful complement of IR spectroscopy.

PMID- 18720780
TI  - [The spectra properties of 2-(2'-hydroxyphenyl)benzothiazole in different
      solvents].
AB  - 2-(2 -hydroxyphenyl)benzothiazole (HBT) is a typical compound with excited--state
      intramolecular proton transfer (ESIPT) effect. The mechanism of the influence of
      the solvent polarity on the ESIPT effect of HBT was investigated by means of
      absorption and fluorescence spectra in different polar solvents. The absorption
      spectra of HBT molecule in all solvents have the similar configuration and are
      mainly situated in the UV region from 260 to 370 nm. The absorption peaks are
      located at 287 and 335 nm and have the decline trend with the increase in the
      solvent polarity. In addition, there is a very weak absorption band at 400 nm and
      it is attributable to the absorption from the keto form of HBT. Under UV
      excitation at 335 nm, the fluorescence spectra in all the solvents were obtained.
      All the fluorescence spectra exhibit dual fluorescence peaks, which are located
      at 385 and 512 nm respectively. The former is attributed to the emission from the
      HBT enol forms, named the normal fluorescence, and the latter the emission from
      the keto tautomer emission, named ESIPT fluorescence. The fluorescence spectra of
      HBT show that the intensity of the normal fluorescence is obviously increased and
      the intensity of the ESIPT fluorescence is decreased with enhancing the polarity
      of the solvents. This indicates that the strong polar solvents are not favorable
      to the ESIPT of HBT. Because the solvated enols in the polar solvent prevent the
      ESIPT from happening, the ESIPT efficiency of HBT in cyclohexane is the largest
      and that of HBT in ethanol is the smallest. The three fluorescence bands of HBT
      in different polarity solvents were observed with 400 nm excitation. One
      fluorescence band at ca. 510 nm is referred to as the ESIPT fluorescence. This
      confirms that the weak absorption at 400 nm results from the keto tautomer and
      the enol and keto forms can coexist under the normal condition, but the enol form
      is the absolutely predominant. In addition, the other two unknown fluorescent
      emission bands appear at 436 and 456 nm respectively. Their possible origin is
      the emission from the deprotonated anion of HBT keto tautomer.

PMID- 18720781
TI  - [Radiative transport and collisional transfer of excitation energy in Cs(6P)
      atoms mixed with N2].
AB  - Applying the CW laser absorption and fluorescence method, the cross sections for
      the fine structure mixing and quenching of the Cs(6P) state, induced by collision
      with N2 molecules, were measured. Cesium atoms were optically excited to the
      6P3/2 state. The excited atom density and spatial distribution were mapped by
      monitoring the absorption of a counterpropagating single mode laser beam, tuned
      to the 6P1 --> 8S(1/2) transitions, which could be translated parallel to the
      pump beam. The transmission factors, which describe the average probability that
      photons emitted within the fluorescence detection region can pass through the
      optically thick vapor without being absorbed, were calculated for 6P --> 6S(1/2)
      transitions. The N2 caused line broadening and therefore increased the effective
      pumping rate and radiative rates. The effective radiative rates were calculated
      for the 6P(J) --> 6S transitions. The fluorescence intensity I895 of the
      sensitized 6P(1/2) --> 6S(1/2) emission was measured as a function of N2 density
      in the range 2 x 10(16) < N < 1.4 x 10(17) cm(-3) at a constant temperature T =
      337 K, which produced cesium density N0 = 1.25 x 10(12) cm(-3). The transparency
      of the cell was obtained by the absorption of light beam passing the cell. The
      transparency is not a simple function of N2 density. It was found that the
      quantity N/I895 (I895 being corrected for the cell transparency) exhibited a
      parabolic dependence on N, confirming that the quenching of the 6P(J) states is
      due to collision with N2 molecules instead of Cs ground state atoms. The
      coefficients of the second-order polynomial fitted through the measured data
      yielded the cross sections sigma3/2 --> 1/2 = (0.42 +/- 0.17) x 10(-16) cm2 and
      sigmaD = (1.31 +/- 0.52) x 10(-16) cm2 for the 6P(J) fine-structure mixing and
      quenching, respectively, due to collision with N2 molecules. The quenching rate
      coefficient is about 3 times larger than the rate coefficient for the fine
      structure mixing. Our values for these cross sections are in agreement, within
      combined error bars, with the values we have recently obtained under different
      experimental conditions.

PMID- 18720782
TI  - [Study on illuminant spectrum qualifications for collecting tongue condition].
AB  - The traditional light sources in the diagnostic method of tongue collection such
      as daylight or even candles are easily affected by weather and environment. It
      isn't favorable for doctors to obtain the accurate information of the tongue
      condition. The authors' introduce the electric light sources to compensate or
      replace daylight to obtain stable and real tongue image and scientific results.
      Lighted by lamps with different radiation spectrum power distribution property,
      various color rendition and color temperature, the same object will indicate
      different colors. In this study, spectrum analysis is carried out on four
      fluorescent lamps and the research is based on iamge identification techniques of
      tongue color. Applying the methods of spectrum analysis, choose the best one in
      four illuminants with their specific spectrum by testing instruments and
      comparing with the results using several spectrum parameters and chromatic
      coordinates tolerance ellipses. Result showed PHILIPS YPZ220/18-3U. RR. D (with
      the correlative color temperature 6 500 K) lamp which has the most similar
      spectrum property with daylight can be used as standard lamp. The research
      provides the theoretic and experimental basis for choosing electric light sources
      to replace daylight.

PMID- 18720783
TI  - [A method of recognizing biology surface spectrum using cascade-connection
      artificial neural nets].
AB  - A method of recognizing the visible spectrum of micro-areas on the biological
      surface with cascade-connection artificial neural nets is presented in the
      present paper. The visible spectra of spots on apples' pericarp, ranging from 500
      to 730 nm, were obtained with a fiber-probe spectrometer, and a new spectrum
      recognition system consisting of three-level cascade-connection neural nets was
      set up. The experiments show that the spectra of rotten, scar and bumped spot on
      an apple's pericarp can be recognized by the spectrum recognition system, and the
      recognition accuracy is higher than 85% even when noise level is 15%. The new
      recognition system overcomes the disadvantages of poor accuracy and poor anti
      noise with the traditional system based on single cascade neural nets. Finally, a
      new method of expression of recognition results was proved. The method is based
      on the conception of degree of membership in fuzzing mathematics, and through it
      the recognition results can be expressed exactly and objectively.

PMID- 18720784
TI  - [Spectral properties of two-dimensional photonic crystal quantum well
      structures].
AB  - In the present paper, the spectral properties of two-dimensional (2D) photonic
      crystal quantum well structures were studied numerically. The structures consist
      of a 2D photonic crystal (PC) with square lattice of parallel dielectric circular
      columns in air and some middle layers of columns are removed. Similar to the
      electrons in semiconductor quantum wells, the photonic bandgap (PBG) in PC can
      act as a potential barrier to photons, which gives rise to quantized photonic
      states in the PBG region. Photonic band structures were calculated using plane
      wave expansion method and transmission spectra were obtained using transfer
      matrix method. The results show that discrete transmission peaks appear in PBG
      region. More transmission peaks arise with the increase of the well layer and the
      strength decreases with the increase in the potential layer width. The
      relationships between the frequency of transmission peaks and the width of well
      layer were also discussed.

PMID- 18720785
TI  - [Effect of spectra on growth of chlorella and isochrysis].
AB  - Focusing on the speed and efficiency, the effects of different spectra on the
      growth of chlorella vulgaris and isochrysis galbana Parke 8701 were investigated
      by using monochromatic LED (light-emitting diode) and fluorescent lamp as light
      sources. It was concluded that continuous spectra accelerate the top-growth-rate,
      blue light has the best efficiency, and the combination of them can obtain a good
      balance of speed and efficiency. For the purpose of measuring spectra as a
      parameter of irradiation quantitatively, spectra-absorbability-coefficient
      defined as the quanta-absorbability- efficiency of spectra for algae was
      calculated by means of absorption spectra of algae and emission spectra of light
      sources. Compared with the experimental results the coefficients of different
      light sources have a positive correlation to their efficiency for growth, so the
      coefficient can be used to elementarily quantify the relation between the spectra
      and the efficiency for growth.

PMID- 18720786
TI  - [Model building and optimization of ultrathin silver films by spectroscopic
      ellipsometry].
AB  - Ultrathin silver films (4.0, 6.2, 12.5, 26.2, 30.0 and 40.6 nm) were prepared by
      direct current sputtering deposition. The thicknesses and optical constants of
      the films were studied by spectroscopic ellipsometry. The Drude model combined
      with Lorentz Oscillator model was used in the optimization of the ellipsometric
      data. The results show that surface plasma resonance absorption (SPR) peaks
      appear in the spectra of extinction coefficient k for samples 1, 2, 3 and 4. The
      peak shifts to shorter wavelength with the reduction in film thickness. The
      wavelengths of the SPR for different films were calculated by the SPR theory and
      also compared with the experimental data.

PMID- 18720787
TI  - [Spectroscopic properties of Er3+-doped germanium bismuthate glass].
AB  - Er(3+)-Doped Germanium Bismuthate Glass was fabricated and characterized. The
      absorption spectrum and up-conversion spectrum of glass were studied. The Judd
      Oflet intensity parameters omega(t) (t = 2, 4, 6), determined based on Judd-Ofelt
      theory, were found to be omega2 = 3.35 x 10(-20) cm2, omega4 = 1.34 x 10(-20)
      cm2, omega6 = 0.67 x 10(-20) cm2. Frequency up-conversion of Er(3+)-doped
      germanium bismuthate glass has been investigated. The up-conversion mechanisms
      are discussed under 808 nm and 980 nm excitation. Stimulated emission cross
      section of 4I(13/2) --> 4I(15/2) transition was calculated by McCumber theory.
      Compared to other host glasses, the emission property of Er(3+)-doped germanium
      bismuthate glasses has advantage over those of silicate, phosphate and germinate
      glasses. Er(3+)-doped germanium bismuth glasses are promising upconversion
      optical and optic-communication materials.

PMID- 18720788
TI  - [Experimental study on glucose solution by laser-induced breakdown spectroscopy].
AB  - The glucose solution was broken down by focusing the 1.064 microm beam of a Nd :
      YAG laser, and the plasma was produced. The spectral signals were detected by an
      experimental setup including spectrograph and ICCD. The spectral line at 247.86
      nm was identified as the characteristic of glucose by contrasting the spectra of
      glucose solution and pure water. Comparing the spectral intensities of three
      kinds of glucose solution with different concentrations (3%, 6% and 9%), the
      experimental result showed that the bigger the concentration, the stronger the
      spectral intensity,and the characteristic spectral intensities with the three
      concentrations present the trend of logarithm increase. At the same
      concentration, the time evolution curve of the characteristic spectra was
      obtained by changing the delay time of ICCD. It is concluded that the intensity
      of the characteristic spectra first increases and then decreases with the delay
      time. With the glucose solution concentration altering, the decay time of the
      characteristic spectra is nearly fixed, meaning that the decay time is
      independent of the concentration. The decay time of the characteristic spectra is
      about 300 ns. Furthermore, it was found that the characteristic spectral
      intensities of glucose solution with different concentrations reach the maximum
      at the same delay time.

PMID- 18720789
TI  - [Observation and simulation of bi-directional spectral reflectance on different
      type of soils].
AB  - Knowledge of radiative transfer over bare soils is a prerequisite to addressing
      vegetation canopies and predicting soil properties by remote sensing. In the
      present study, the change in the spectral reflectance for three soils (i. e. red
      soil, paddy soil and coastal saline soil) with different view zenith and azimuth
      angles in the visible band (620 nm) and Landsat TM4 near infrared wavebands (760
      900 nm) was measured in laboratory. The results showed that soil reflectance
      increased with increasing off-nadir view angle for all azimuth directions and
      soil bidirectional reflectance was azimuthally symmetric. The reflectance was
      highest in backscattering direction and lowest in forward-scattering direction.
      The bidirectional reflectance was simulated well using the Hapke model derived
      from the radiative transfer theory. The root mean square errors (RMSE) were
      0.003, 0.002 and 0.004 and the correlation coefficients were 0.995, 0.998 and
      0.998 in simulating bidirectional reflectance in visible wavebands for red soil,
      paddy soil and coastal saline soil, respectively; RMSE were 0.004, 0.006 and
      0.005 and the correlation coefficients were 0.997, 0.996 and 0.998 in simulating
      bidirectional reflectance in NIR wavebands for these soils, respectively. It is
      stated clearly that Hapke model could be used to simulate the whole spectra
      curve, then to retrieve the soil surface characteristics.

PMID- 18720790
TI  - [The effect of temperature on the 4f5d emission of Pr3+ in the Pr3+-doped
      SrAl12O19].
AB  - The emission spectra of SrAl12O19 : Pr3+ at temperature from 308 to 483 K were
      investigated under vacuum ultraviolet excitation. Both the dipole-forbidden 4f2 -
      > 4f2 transition and the dipole-allowed 4f5d --> 4f2 transitions were observed.
      The intensity of the 4f5d --> 4f2 emission relative to that of the 4f2 --> 4f2
      emission increased with increasing temperature. A thermal equilibrium model was
      applied to the system consisting of the 1S0 state and the lowest 4f5d states of
      Pr3+, and the temperature dependence of emission spectra of Pr3+ in the Pr(3+)
      doped SrAl12O19 was well explained.

PMID- 18720791
TI  - [The study of ultra-fine diamond powder used in magnetic head polishing slurry].
AB  - In the present paper, atomic absorption spectrometry(AAS), inductively-coupled
      plasma mass spectrometry (ICP-MS), transmission electron microscopy (TEM), X-ray
      diffraction (XRD) and laser Raman spectroscopy (RM) were employed to study the
      commercial ultra-fine diamond powders prepared by the static pressure-catalyst
      method and used in magnetic head polishing slurry. The results of AAS and ICP-MS
      indicated that there were silicon oxide, Fe, Ni, Al and some other metal elements
      in the ultra-fine powders. XRD patterns showed the peaks of SiO2 at 2theta = 35.6
      degrees, 39.4 degrees and 59.7 degrees and diamond sharp peaks in agreement with
      the results above. Diamond sharp peaks implied perfect crystal and high-hardness
      beneficial to high-efficiency in polishing. The broader Raman band of graphite at
      1 592 cm(-1) observed by Raman analysis proved graphite existing in the diamond
      powders. In the TEM images, the size of ultra-fine powders was estimated between
      0.1 and 0.5 microm distributed in a wide scope, however, sharp edges of the
      powder particles was useful to polish. The ultra-fine diamond powders have many
      advantages, for example, high-hardness, well abrasion performance, high-polishing
      efficiency and being useful in magnetic head polishing slurry. But, the
      impurities influence the polishing efficiency, shortening its service life and
      the wide distribution reduces the polishing precision. Consequently, before use
      the powders must be purified and classified. The purity demands is 99.9% and
      trace silicon oxide under 0.01% should be reached. The classification demands
      that the particle distribution should be in a narrower scope, with the mean size
      of 100 nm and the percentage of particles lager than 200 nm not over 2%.

PMID- 18720792
TI  - [The influence of boric acid content on luminescent properties of SrAl2O4].
AB  - Long persistence phosphor powder of E2+, Dy3+ co-doped SrAl2O4 were prepared by
      combustion method. The influence of boric acid with different contents on the
      luminescent properties of Eu2+, Dy3+ co-doped alkaline earth aluminates were
      studied. To analyze the role of B2O3, phase identification was carried out by X
      ray powder diffraction, emission spectra were recorded using a luminescence
      spectrometer, and luminescence photos were taken in a dark room after being
      excited by UV. The results indicated that the lambda(em) of the sample with
      content of 0.8 is 518 nm, which is the typical emission of Eu2+ 4f5d --> 4f and
      is a wide emission spectrum. There are two peaks in the emission spectra of the
      sample with content of 2, one is at 518 nm, and the other is at 487 nm, both of
      which are weak. The whole spectral line is a declining line. With the increase in
      boric acid content, the luminescence property and appearance character of Eu2+,
      Dy3+ co-doped strontium aluminates long persistence phosphor were different. In
      some range, with the increase in boric acid content, luminescence property and
      luminescence intensity were increased, and the sintering temperature was lowd.

PMID- 18720793
TI  - [PEG assisted hydrothermal synthesis of LaPO4 : Eu3+ nanoparticles].
AB  - The present reports a hydrothermal process to synthesize the precursor of Eu(3+)
      doped LaPO4 nanoparticles with PEG2000 used as additive. SEM shows that the
      nanoparticles are similar to spheres. The Eu(3+-)doped LaPO4 phosphor was
      characterized by powder X-ray diffractometer. According to our measurements with
      XRD, the products belong to monoclinic monazite type, and the samples were well
      crystallized after sintering at 700 degrees C for 2 h. The effects of synthesis
      condition, sintering temperature and time on the luminescence of the samples were
      investigated. The luminescence data indicated that the optimum condition for
      synthesizing the precursor was at 180 degrees C for 14 h, and the optimum
      condition for heat-treatment of the precursor was at 850 degrees C for 1 hour.
      The effects of different contents of Eu3+ on the luminescence of LaPO4 : EuO3+
      nanoparticles were also investigated, and the results showed that the
      luminescence intensity was enhanced with the slight increase in the Eu3+ content,
      and the optimum Eu(3+)-doping concentration was 4% (mole fraction).

PMID- 18720794
TI  - [Chemiluminescence determination of 6-mercaptopurine in the luminol-potassium
      ferricyanide system].
AB  - A novel chemiluminescence (CL) method to determine 6-mercaptopurine (6-MP) is
      described, based on the catalytic effect of 6-MP on the CL reaction of luminol
      with K3Fe(C-N)6 in a flow system. Under optimal experimental conditions, the
      calibration graph is linear in the range of 1.02 x 10(-7) to 1.02 x 10(-9) mol x
      L(-1) 6-MP. The linear regression equation was Y = 36.315c + 140.72, where Y is
      the relative emission intensity and c is the concentration of 6-MP expressed in
      10(-8) mol x L(-1) and the correlation coefficient is 0. 998 2 with the detection
      limits of 6. 33 X 10(-10) mol x L(-1) (S/N = 3). CL peak-height precision is
      3.54% of RSD (n = 12) for a level of 2.0 x 10(-9) mol x L(-1). This method
      satisfactorily provides a fast, simple, sensible and favorable technique for the
      determination of 6-MP in synthesized samples in implementation. Moreover, the
      possible mechanism of CL enhancement was briefly discussed. Obviously, the
      reaction was related to the formation of free radicals. Thus, the CL emission
      could preliminarily be attributed to the process of energy transfer due to O2.
      radical and * OH radical resulting from the oxidation product of 6-MP by
      K3Fe(CN)6, which acts as an active intermediate that reacts with luminol, leading
      to the formation of excited luminol molecule, which gives out an emission when it
      returns to its ground state.

PMID- 18720795
TI  - [Synthesis, characterization and antimicrobial activity of konjac glucomannan
      derivative with quaternary ammonium salts].
AB  - Methacryloxylethyl tetradecyl dimethyl ammonium bromide was grafted onto konjac
      glucomannan using ceric ammonium nitrate as an initiator, and the konjac
      glucomannan derivative with quaternary ammonium salts was obtained. The konjac
      glucomannan derivative was investigated by hydrogen nuclear magnetic resonance
      spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FTIR),
      differential scanning calorimeter (DSC), and Zeta sizer nano series. The
      antimicrobial properties of the konjac glucomannan derivative against selected
      microorganisms were tested by the quantitative suspension method. The results
      revealed that (1) methacryloxylethyl tetradecyl dimethyl ammonium bromide can be
      grafted onto the surface of the konjac glucomannan, and the percentage grafting
      increases with increasing the amount of methacryloxylethyl tetradecyl dimethyl
      ammonium bromide. (2) The Zeta potential showed that the isoelectric point of the
      konjac glucomannan and the modified konjac glucomannan is pH 4. 5 and pH 9. 9,
      respectively. The shift of the isoelectric point is due to the quaternary
      ammonium groups. (3) The obtained konjac glucomannan derivative has significant
      inhibition effect on the growth of microorganisms, and the bactericidal rates in
      15 min for E. coil (8099), S. aureus (ATCC 6538) and C. albicans (ATCC10231) were
      99.99%, 99.99% and 98.13%, respectively.

PMID- 18720796
TI  - [Infrared study on adsorption of O3 at SnO2 surface].
AB  - SnO2 was prepared by precipitation method and mental oxides modified SnO2
      catalysts were prepared by coprecipitation method. High concentration molasses
      fermentation wastewater degradation by SnO2 catalyzed ozonation was used as a
      probe reaction and IR spectra were used to study the adsorption of O3 at SnO2 and
      different metal oxides modification SnO2 surface. The results showed, that in the
      infrared absorption spectra of adsorption of O3 prepared by pure O2 at SnO2
      catalyst surface, two obvious bidentate absorption double peaks were found at 1
      027 and 1 055 cm(-1), and 2 099 and 2 122 cm(-1), respectively. However, there
      was competitive adsorption between O3 prepared by air, and CO and CO2. Then the
      O3 adsorption decreased, leading to the decrease in the degradation of molasses
      fermentation wastewater by SnO2 catalytic ozonation, and after 60 min reaction,
      the degradation rate by pure oxygen as oxygen source was 79.2%. It was 33.1% more
      by air as oxygen source. Similar strength adsorption peaks in the infrared
      spectra were found at 2 236, 2213 cm(-1) and 1 628, 1 599 cm (-1) with Fe2O3,
      NiO, CuO, ZnO, MgO, SrO and BaO modified SnO2. But the adsorption of CO2 and CO
      was different on modifier-SnO2, There was a wide absorption peak at 1 580-1 070
      cm(-1) in the infrared spectra of transition metal modified SnO2, and two new
      peaks at 1 298 and 1 274 cm(-1) were found between 1 580 and 1 070 cm(-1) in the
      infrared spectra of alkaline-earth metals modified SnO2 catalysts. These changes
      leaded to a different catalytic ozonation activity of modifier-SnO2, the results
      of molasses fermentation wastewater degradation by ozone combined with alkaline
      earth metal modified SnO2 was obviously better than ozone combined with
      transition metal modified SnO2. And among them, the ozonation catalytic activity
      of BaO-SnO2 was the best.

PMID- 18720797
TI  - [The structure and properties of metal-free 1, 8, 15, 22-tetrakis (3-pentyloxy)
      phthalocyanine complex and study of its IR spectra].
AB  - Density functional theory calculations were carried out to study the molecular
      structure, molecular orbital, atomic charge, and infrared spectra of metal-free
      1, 8, 15, 22-tetrakis(3-pentyloxy) phthalocyanine using B3LYP method with the 6
      31G (d) basis set. The optimized molecular geometry is in good agreement with the
      result from X-ray deterimination, and the differences between the bond lengths
      from calculation and X-ray crystallography structure for the framework of
      phthalocyanine are less than 0.002 nn. It was also found that there is a good
      consistency between the calculated and experimental IR data. The calculated
      structure and IR spectra were fairly compared with the X-ray crystallography
      structure and experimental IR spectra to verify the reliability of employed B3LYP
      method and 6-31G(d) basis set. It is worth noting that the 3-pentyloxy groups at
      the alpha position have significant influence on the structure and properties of
      metal-free pthalocyanine, for example, both the energies of HOMO and LUMO
      increase, however, the gap between HOMO and LUMO decreases, which results in the
      decrease of the 1, 8, 15,22-tetrakis(3- pentyloxy)phthalocyanine stability. The
      important peaks in the IR spectra were also assigned and analyzed in detail
      according to the calculations.

PMID- 18720798
TI  - [Determination of main fiber compositions of alfalfa hay by near infrared
      reflectance spectroscopy].
AB  - Sixty alfalfa samples, with different growth stage, cultivars, and preparing
      method (drying by oven, shade and sun), were selected to study the potential of
      determination of cellulose, hemicellulose and lignin content in the present
      research. The result showed that the correlation coefficient of cross-validation
      (R(cv)), determination coefficient of external validation(r2) and the ratio of
      standard deviation to root mean square error of prediction (RPD) of cellulose and
      lignin were 0.97, 0.97 and 4.44, and 0.94, 0.94 and 4.08, respectively. This
      indicated the feasibility of determining cellulose and lignin content of alfalfa
      using near infrared reflectance spectroscopy. Hemicellulose was not predicted
      accurately by NIRS in this study, due to the lowest accuracy (R(cv) = 0.39, r2 =
      0.29, RPD = 1.09). The exact determination of cellulose and lignin using near
      infrared reflectance spectroscopy will be useful to quality control in alfalfa
      production and quickly analyzing the fiber composition of alfalfa samples
      breeding research.

PMID- 18720799
TI  - [The study of infrared absorption spectrum of diamond during growth by FTIR].
AB  - The diamond thin films were deposited on silicon substrates under invariable
      conditions of process pressure, substrate temperature negative direct-current
      (dc) bias of substrate and microwave power while the rations of methane (CH4) to
      hydrogen (H2) changing from 3% to 5% and 9% using electron-cyclotron-resonance
      microwave plasma-assisted chemical vapor deposition technique (ECRCVD). In situ
      Fourier transform infrared spectroscopy (FTIR) have been used to study the plasma
      species absorbed on the substrate surfaces as well as the species above the
      substrates surfaces both before and during the nucleation and film growth. It is
      demonstrated that these techniques can provide useful information on the early
      stages of diamond growth. When correlated with film properties measured by Raman
      spectroscopy and scanning electron microscopy, the results from FTIR indicate
      that the absorption of the graphitic and diamond phases are related to the ratio
      of CH4 to H2 and can be identified at the early stages of film growth.

PMID- 18720800
TI  - [A method of eliminating the water vapor interference simultaneously in open path
      FTIR measurement by instrumental line shape correction].
AB  - Water vapor absorption, which exists in mid-infrared region, is an interferential
      element for infrared spectra analysis. A new method, which can be used to
      eliminate the water vapor interference in FTIR measurement, is presented. To
      calculate the high resolution absorbance of water vapor, a fast line by line
      method which computed with the HITRAN database (eg. line strength, self
      broadening, air broadening, etc) and meteorological parameters (eg. temperature,
      pressure, and relative humidity) was used. After convolving with Instrumental
      line shape (eg. divergence angle, resolution, etc), the absorbance of water vapor
      was then transferred from high resolution to low resolution, which matched the
      instrumental parameters. After the acquirement of water vapor absorbance
      spectrum, it will be subtracted from the measured spectrum to calculate the
      spectrum with the water vapor was eliminated. In the present work, analysis of
      measured data from open path FTIR is described. Only the absorbing character and
      noise was left in the spectrum after eliminating the water vapor interference.
      Consequently, this method has an ideal effect on water vapor elimination when
      there is no dryer can be used, especially in the case of open path FTIR
      measurement.

PMID- 18720801
TI  - [Applied study on clustering of variables around latent components method in
      wavelength region selection with near-infrared spectroscopy].
AB  - The present paper introduced the principle of clustering of variables around
      latent components method, and used this method in selecting spectrum range of the
      NIR quantitative analysis models. Taking tobacco samples as experiment materials,
      we dealed with 107 sample spectra, divided the spectra into 5 clusters, and
      explained the information reflected by each of these 5 clusters in terms of
      chemistry. On this basis, we chose the corresponding wavelength range to set up
      the quantitative models of the total sugar, reducing sugar and nicotine by PLS
      method. Compared with the model based on the full NIR spectral range, Rtraining
      of the models based on the chosen spectral range rose from 0.977 1, 0.917 2 and
      0.987 4 to 0.995 5, 0.975 1 and 0.994 4; Rtest rose from 0.977 8, 0.941 2 and
      0.993 2 to 0.992 7, 0.967 9 and 0.994 0; RMSECV dropped from 1.09, 1.43, 0.14 to
      1.05, 1.05 and 0.13, RMSEP dropped from 0.92, 1.17 and 0.16 to 0.39, 0.63 and
      0.11 and the D value dropped from 1.274%, 1.972% and 0.829% to 0.711%, 0.843% and
      0.768% for the total sugar, reducing sugar and nicotine, respectively. These data
      indicated that this method can improve the forecasting precision and stability of
      the model, so offers certain guidance on practical application.

PMID- 18720802
TI  - [Application of Vis/NIR diffuse reflectance spectroscopy to the detection and
      identification of transgenic tomato leaf].
AB  - The feasibility of Vis/NIR spectroscopy technique for rapid and non-invasive
      detection of transgenic tomato leaves from conventional ones was investigated by
      means of spectral diffuse reflectance mode. A total of 68 samples (38 transgenic
      ones and 30 non-transgenic ones) were used for classification. The calibration
      and validation results were analyzed via discriminant analysis (DA) and partial
      least squares (PLS) discriminant method using TQ 6.2. 1 quantitative software.
      Models based on the different spectral pre-processing methods (multiplicative
      signal correction (MSC), first and second derivative) were compared. It was found
      that the classification accuracy using DA was higher than that using PLS and the
      best results were gained by using spectra after MSC with InGaAs detector and the
      classification accuracy was 89.7% (accuracy of 86.8% for transgenic samples and
      93.3% for non-transgenic ones). The results show that Vis-NIR diffuse reflectance
      spectroscopy technique is a feasible and fast method for non-invasive detection
      of transgenic and non-transgenic tomato leaves.

PMID- 18720803
TI  - [FTIR spectroscopic characterization of chromium-induced changes in root cell
      wall of plants].
AB  - Due to its wide industrial use, chromium is considered a serious environmental
      pollutant. Contamination of soil and water by chromium (Cr) is of recent concern.
      Chromium mainly accumulates in root in plants, and the change in compounds of the
      root cell wall have a close relation with the Cr accumulation. Compared with the
      other identification methods, the identification of the Chinese traditional and
      herbal drugs using Fourier transform infrared spectrometer with OMNI collector is
      simple and convenient, fast and accurate. In the present paper, the spectra of
      cell wall of Cr-treated root and control of Eichhornia crassipes and
      Alternanthera philoxeroides were determined. Absorption peaks were identified to
      the corresponding functional groups and half-quantitative analysis was also used.
      The results showed that a significant shift of -OH absorption peaks can be seen
      when comparing the FTIR spectra of control and Cr-treated plants, and the
      absorbency of -OH and COO- groups went up in E. crassipes root cell wall while
      droped in A. philoxeroides root cell wall. It is suggested that -OH and COO
      groups were referred in binding Cr6+ in aqueous solutions, and this may be
      included in the mechanism of Cr accumulation in E. crassipes roots. Therefore,
      FTIR spectrometry could be widely used to monitor changes in chemical composition
      of plant parts under stresses and environmental restoration.

PMID- 18720804
TI  - [Application of infrared spectroscopy technique to protein content fast
      measurement in milk powder based on support vector machines].
AB  - In the present study, the JASCO Model FTIR-4 000 fourier transform infrared
      spectrometer (Japan) was used, with a valid range of 7 800-350 cm(-1). Seven
      brands of milk powder were bought in a local supermarket. Milk powder was
      compressed into a uniform tablet with a diameter of 5 mm and a thickness of 2 mm,
      and then scanned by the spectrometer. Each sample was scanned 40 times and the
      data were averaged. About 60 samples were measured for each brand, and data for
      409 samples were obtained. NIRS analysis was based on the range of 4 000 to 6 666
      cm(-1), while MIRS analysis was between 400 and 4 000 cm(-1). The protein content
      was determined by kjeldahl method and the factor 6.38 was used to convert the
      nitrogen values to protein. The protein content value is the weight of protein
      per 100 g of milk powder. The NIR data of the milk powder exhibited slight
      differences. Univariate analysis was not really appropriate for analyzing the
      data sets. From NIRS region, it could be observed that the trend of different
      curves is similar. The one around 4 312 cm(-1) embodies the vibration of protein.
      From MIRS region, it could be determined that there are many differences between
      transmission value curves. Two troughs around 1 545 and 1 656 cm(-1) stand for
      the vibration of amide I and II bands of protein. The smoothing way of Savitzky
      Golay with 3 segments and zero polynomials and multiplicative scatter correction
      (MSC) were applied for denoising. First 8 important principle components (PCs),
      which were obtained from principle component analysis (PCA), were the optimal
      input feature subset. Least-squares support vector machines was applied to build
      the protein prediction model based on infrared spectral transmission value. The
      prediction result was better than that of traditional PLS regression model as the
      determination coefficient for prediction (R(p)2) is 0.951 7 and root mean square
      error for prediction (RMSEP) is 0.520 201. These indicate that LS-SVM is a
      powerful tool for spectral analysis. Moreover, the study compared the prediction
      results based on near infrared spectral data and mid-infrared spectral data. The
      results showed that the performance of the model with mid-infrared spectral data
      was better than the one with near infrared spectra data. It was concluded that
      infrared spectroscopy technique can do the quantification of protein content in
      milk powder fast and non-destructively and the process was simple and easy to
      operate. The results of this study can be used for the design of a simple and non
      destructive spectra sensor for the quantitative of protein content in milk
      powder.

PMID- 18720805
TI  - [Using Fourier transform to analyse differential optical absorption spectrum].
AB  - According to the theory of differential optical absorption spectral technique,
      the differential optical absorption spectral monitoring equipment was designed.
      Aiming at two kinds of main pollutants, SO2 and NO2, in the atmosphere, this
      technique was used to monitor them. The present article puts forward the signal
      analysis method of Fourier transformation to process the above-mentioned two
      kinds of absorption spectra. The two approaches contain the removeal of noise and
      the fitting of the slow variety. On the frequency chart after the spectrum was
      transformed, the low frequency corresponded to the slow variety part and the high
      frequency corresponded to the noise part of the original spectrum, so through
      intercepting a certain frequency segment and using inverse Fourier transformation
      the slow variety part of the low frequency and the noise part of the high
      frequency of the absorption spectrum could be subtracted. After farther
      processing we can get a higher resolution differential absorption spectrum of the
      gas. According to the strength of the spectrum, we can calculate the
      concentration of the gas. After analysis and comparison with the conventional
      method, it is considered a new processing method of differential optical
      absorption spectral technique, and the method can fit the slow variety much
      better.

PMID- 18720806
TI  - [Development of aperture probe near-field Raman spectroscopy and microscopy].
AB  - The appearance of near-field Raman spectroscopy that is based on aperture probe
      scanning near-field optical microscopy makes the resolution of Raman spectroscopy
      beyond the optical diffraction limitation. It provided a powerful tool to probe
      chemical information of sample on subwavelength scale. The present article
      illustrates the influence of probe character on near field Raman spectroscopy.
      Furthermore, the development over ten years in chemical resolution imaging on
      nanoscale, special properties of liquid-liquid interface, exploring SERS
      mechanism and observing hotspots beneath subwavelength scale etc. were introduced
      in detail.

PMID- 18720807
TI  - [Study on Raman linear model of human breast tissue].
AB  - A linear regression model for Raman spectra of human breast tissue was developed
      with 10 basis spectra which were derived from the spectra of fat, cell cytoplasm,
      collagen, beta-carotene, DNA and cholesterol etc. This model was tested
      statistically with more than 2 000 spectra collected from both normal and tumor
      breast tissue samples. The confidence of F-test for the model significance was 1
      to all the spectra and the average of multiple determination coefficients
      measuring the fit goodness was 0.95. The normalized fit coefficients reflected,
      to a certain extent, the relative quantities of the Raman-active components in
      tissue represented by the basis spectra. In comparison with normal breast tissue,
      the coefficients of the cell cytoplasm and DNA basis spectra increased apparently
      for the tumor one, and the coefficient of fat basis spectrum changed reversely,
      which was easily understood with the known pathological changes in the tissue.
      Mapping spectra were also fitted with this model. This work is helpful to
      understanding the biochemical/morphological changes in the breast tumor tissues
      and to developing the Raman diagnostic method for breast tumor.

PMID- 18720808
TI  - [Near infrared Raman spectra analysis of rhizoma dioscoreae].
AB  - A novel and compact near-infrared (NIR) Raman system was developed using 785 nm
      diode laser, volume-phase technology holographic system, and NIR intensified
      charge-coupled device (CCD). The Raman spectra and first derivative spectra of
      rhizoma dioscoreae were obtained. The Raman spectra of rhizoma dioscoreae showed
      three strong characteristic peaks at 477, 863 and 936 cm(-1), respectively. The
      major ingredients are protein, amino acid, starch, polysaccharides and so on,
      matching the known basic biochemical composition of rhizoma dioscoreae. In the
      first derivative spectra of rhizoma dioscoreae, the distinguishing characteristic
      peaks appeared at 467, 484, 870 and 943 cm(-1). Contrasted with rhizoma
      dioscoreae Raman spectra in the ranges of 600 to 800 cm(-1) and 1 000 to 1 400
      cm(-1), the changes in rhizoma dioscoreae Raman first derivative spectra are
      represented more clearly than the rhizoma dioscoreae Raman spectra. So the
      rhizoma dioscoreae Raman first derivative spectra can be an accurate
      supplementary analysis method to the rhizoma dioscoreae Raman spectra.

PMID- 18720809
TI  - [Wavebands selection for rice information extraction based on spectral bands
      inter-correlation].
AB  - The hyperspectral remote sensing data usually involve hundreds or even thousands
      of narrow bands, which may be crucial for providing additional information with
      significant improvements over broad bands in quantifying biophysical and
      biochemical variables of agricultural crop. However, the huge data generated by
      hyperspectral systems, and the problems this presents for storage and analysis,
      have far prevented the routine use of such data. The objective of the present
      research was to identify the spectral bands in the visible and near-infrared
      range that were suitable for the study of rice. The hyperspectral reflectance of
      canopy in different development stages was measured in experimental field using a
      1 nm-wide spectroradiometer but was aggregated to 10 nm-wide bandwidths to match
      the first spaceborne hyperspectral sensor, Hyperion. The correlation
      coefficients(r) between all the combinations of spectral bands were computed, and
      then they were converted to R2 , which constituted R2 matrices. The matrices were
      plotted against wavebands. The criterion of band selection is that the lower the
      R2 value, the less the redundancy between two wavebands while the higher R2
      indicates that there is redundant information between two wavebands. According to
      the criterion, the wavebands corresponding to the first 100 minimum R2 values
      were selected from all canopy spectra collected on different dates. And then
      these bands were analyzed. The results indicate that the visible and infrared
      (NIR and SWIR) themselves contain redundant information. The wavebands containing
      abundant information of rice are located in specific bands in the longer
      wavelength portion of the visible region, with secondary clusters in red edge
      region, in strongly reflective near-infrared region with relatively higher
      reflectance, in one particular section of short wave near-infrared (SWIR) (1 530
      nm) and in the second maximum reflectance region of SWIR (2 215 nm). Compared
      with the selected bands with other vegetation, rice seems to have three spectral
      regions of 400-410 nm, 630-650 nm and 1 520-1 540 nm, which exclusively depict
      the characteristics of rice. Moreover, this research identified 17 spectral bands
      in the visible and near-infrared region, which were 405, 565, 585, 605, 620, 640,
      660, 680, 695, 705, 720, 740, 865, 910, 1 085, 1 530 and 2 215 nm. These bands
      contain the majority of the rice information content. A reduction in band number
      without significant information loss is important because it makes it possible to
      achieve fine spatial resolution without sacrificing the ability to characterize
      rice status.

PMID- 18720810
TI  - [Identification methods of crop and weeds based on Vis/NIR spectroscopy and RBF
      NN model].
AB  - The automated recognition of crop and weed by using Vis/NIR spectral in field is
      one of hottest research branches of agriculture engineering. If the recognition
      is efficient and effective, then the variate operations of herbicide or
      fertilizer spraying in field could be realized. Many researches have pointed out
      that the reflectance rate of green plant leaves could be used to identify the
      varieties. As the colors and surface textures of crop and weed were change in
      different living phases, these changes may exert great influence on the
      reflectance spectral of plant leaves. Vis/NIR spectra of three weeds and one crop
      in two different terms were recorded by spectral meter ASD FieldSpec Pro FR. Its
      wave band is from 325 to 1 075 nm. The scan time was 270 ms. The scanning times
      of per sample was set to 30 times. Firstly, 23 days after the planting of
      soybean, some soybean leaves and weeds leave were picked from the field, and
      brought to lab to record spectral. The lighting condition was controlled by an
      artificial halogen bulb. Secondly, on the 45th day, the same experiment was done.
      The three weeds were goose grass, alligator alternanthera and emarginate
      amaranth. The crop was soybean seedling. Totally 378 samples were drawn for two
      terms. As one original reflectance spectrum contains 651 float numbers, the total
      data volume was huge. Using wavelet transform to compress data volume and extract
      characteristic spectral data was tried. The result was 114 float numbers per
      sample. Among them, 250 samples from two terms were used as input data to build
      artificial neural network model, and those left were used to check the
      validation. Radial basis function neural network model is widely used in pattern
      recognition problems. It is a nonlinear and self adaptive parallel. By assigning
      a 1 by 4 vector to each spectral samples, the source data could be used to build
      an RBF-NN model. All the samples were assigned these standard output data. Then,
      the left 128 samples were used to check the performance of the model. The result
      is that only 3 samples from the second term of goose grass were wrongly
      classified as alligator alternanthera, which showed that RBF neural network have
      strong ability to differentiate spectra of species of plant, and that there was
      no massive difference of NIR spectra of one plant in different life periods. This
      demonstrated that the NIR spectra could be used to identify crop from weed with
      no need to care about the living stages of these plants.

PMID- 18720811
TI  - [Effect of acidity on the interaction of Ofloxacin and bovine serum albumin].
AB  - Bovine serum albumin (BSA) exists as N(pH -7.0), B(pH -9.0), and E (pH < 3.5) =
      isomeric forms in the solution of different pH. Acid effect on the structure of
      bovine serum albumin and the interaction of different structure of BSA with
      Ofloxacin were studied by UV-Vis and fluorescence spectroscopy. Based on the
      fluorescence quenching of bovine serum albumin and Forster energy transfer
      mechanism, the quenching constants, energy transfer efficiencies and the binding
      distances were determined at four different pHs. The results showed that
      Ofloxacin has the ability to quench bovine serum albumin fluorescence with the
      optimal condition of fluorescence quenching constants of 1.928 1 x 10(5) L x mo
      l(-1), binding distance of r = 2.55 nm and quenching efficiency of 8.63 x 10(4) L
      x mo x l(-1) at pH 4.9. Non-radiative energy transfer and static quenching were
      the cause of fluorescence quenching. The influence on the binding of Ofloxacin
      and bovine serum albumin under neutral, subacidity and alkalescent conditions was
      not obviously observed, and the electrostatic interaction was not the main force.
      The effect of Oflx on the conformation of BSA was also investigated using
      synchronous fluorescence spectrometry.

PMID- 18720812
TI  - [Study of inversion and classification of particle size distribution under
      dependent model algorithm].
AB  - For the total light scattering particle sizing technique, an inversion and
      classification method was proposed with the dependent model algorithm. The
      measured particle system was inversed simultaneously by different particle
      distribution functions whose mathematic model was known in advance, and then
      classified according to the inversion errors. The simulation experiments
      illustrated that it is feasible to use the inversion errors to determine the
      particle size distribution. The particle size distribution function was obtained
      accurately at only three wavelengths in the visible light range with the genetic
      algorithm, and the inversion results were steady and reliable, which decreased
      the number of multi wavelengths to the greatest extent and increased the
      selectivity of light source. The single peak distribution inversion error was
      less than 5% and the bimodal distribution inversion error was less than 10% when
      5% stochastic noise was put in the transmission extinction measurement values at
      two wavelengths. The running time of this method was less than 2 s. The method
      has advantages of simplicity, rapidity, and suitability for on-line particle size
      measurement.

PMID- 18720813
TI  - [Spectral changes of C-phycocyanin with different molar ratios of SPDP].
AB  - Pure C-phycocyanin was prepared from Spirulina platensis using one-step anion
      exchange chromatography. The C-PC obtained was with an absorption maximum at 620
      nm and a fluorescence emission maximum at 640 nm when excited by 580 nm. SPDP is
      an excellent heterobifunctional crosslinker for thiolating amines. Different
      molar ratios of SPDP have remarkable influence on the absorption and fluorescence
      spectra of C-phycocyanin. The absorption maximum and fluorescence emission
      maximum both decreased and blue-shifted from 640 nm to 630 nm as the molar ratios
      of SPDP increased. It was found that the molar ratios of SPDP to C-phycocyanin
      was not more than 100 was appropriate to being conjugated with other biomolecules
      from the absorption and fluorescence spectra of C-phycocyanin.

PMID- 18720814
TI  - [Synthesis of a novel calix[4]arene derivative with 2-methylquinoline and study
      of it's spectrum character with Zn(II) and Cu(II)].
AB  - A novel calix[4]arene derivative(25,27-two2-methylquinoline t-butylcalix[4]arene,
      MQBC) with the lower rim modified fluorescence groups was synthesized. IR
      spectra, elemental analysis, HNMR spectra and MS were used to determine its
      structure. Meanwhile, the spectra characters of MQBC and the fluorescent
      behaviors of the complex with zinc(II) and copper (II) were investigated, and the
      results showed that the lower rim oxygen atoms in calix[4]arenes may act as
      electrons donor to metal ions. Calix[4] arene was chosen as a basic skeleton of a
      photoresponsive ion carrier because its quinolin derivatives are known to emit
      fluorescence and absorb UV in the solution, and the information of the complex
      with metal ions will be known by spectra experiment. The UV absorbance became
      weak at the band of 226 nm but was enhanced at the band of 315 nm when it bound
      zinc ions, The complex constant(K) and binding ratio(x) were determined to be 2
      064 L x mol(-1) and 1, respectively, by UV spectra experiment. It is expected
      that MQBC will be applied to the detection of trace zinc ions. The fluorecence
      spectra experiment found that MQBC is has feeble fluorecence attributed to the
      intramolecular photoinduced electron transfer(PET) between oxygen atoms and
      methylquinoline groups. When MQBC was combined with zinc(II) and copper(II), it
      caused the inhibiting photoinduced electron transfer process between oxygen atoms
      and methylquinoline groups leading to the enhancement of fluorescence. In
      addition, the photoinduced electron mechanism was discussed and the influence of
      the concentration of zinc(II) and copper(II) on the fluorescence intensities was
      studied.

PMID- 18720815
TI  - [Preparation of TiO2 pillared montmorillonite photocatalyst and its
      photocatalytic activity to degradation reaction of acidic fuchsine by sunlight].
AB  - TiO2 pillared montmorillonite composite photocatalyst was synthesized by acid
      catalyzed sol method and characterized by IR, UV-Vis, TG/DTA, XRD, SEM etc.
      Spectral analyses have demonstrated that TiO2 pillared montmorillonite(Ti-MMT)
      has wider interlayer distance than Na substituted montmorillonite (Na-MMT) and
      higher optical absorption efficiency than nanoscale anatase TiO2. The
      photocatalytic degradation reaction of acidic fuchsine by sunlight was employed
      to evaluate the catalytic activity of the composite catalyst. It was found that,
      besides easy reclaimation, the photocatalytic activity of the catalyst was much
      higher than that of the pure nanosized anatase TiO2. When the addition amount of
      Ti-MMT is 0.2 g x (100 mL)(-1) and pH of acidic fuchsine solution is 3, the dye
      could be degraded thoroughly in 40 min and the degradation reaction obeys
      Langmuir- Hinshelwood equation.

PMID- 18720816
TI  - [A novel analyzing method for the signal denoising of DNA sequencing].
AB  - Fluorescence signals in DNA sequencing are often contaminated by noise, which has
      negative influence on the accuracy and detection limit of analysis. Wavelet
      analysis has excellent time and frequency domain resolution for signal denoising
      compared to other conventional filtering methods. Before the signal denoising
      process, a key problem is how to choose a suitable wavelet base, decomposition
      level and denoising threshold, which have great influence on the quality of
      signal denoising. In order to construct the same noise model as that in
      experiment and evaluate the denoising algorithm precisely, a novel method is
      presented: the real noise signal acquired from the experimental system was added
      to an ideal signal to simulate a noisy DNA sequencing signal, thus the denoising
      efficiency could be evaluated accurately. The denoising results indicate that
      using sym 7 wavelet base, decomposition level at 5 and using fixed form soft
      threshold can effectively reduce the noise. After being processed, the SNR was
      improved more than 5 times. When the same algorithm was applied to the
      experimental DNA sequencing data, the results were more credible than those
      obtained through other algorithms based on the random noise model.

PMID- 18720817
TI  - [Three dimensional fluorescence excitation-emission matrix spectrum of dissolved
      organic substance in marine microalgaes growth process].
AB  - The three-dimensional fluorescence spectrum was used to detect the changes in
      dissolved organic substances from the cultured Skeletonema costatum , Alexandrium
      tamarense, Alexandrium mimutum, Scrippsiella trochodea, Prorocentrum donghaiense
      and Prorocentrum micans. The result indicates that all of the miroalgaes can
      produce FDOM in the growth courses. Diatom such as Skeletonema costatum can
      produce humic-like FDOM. However dinoflagellate can produce protein-like FDOM at
      exponential growth phase. When the algae grows into decadency phase, the
      intensity of humic-like and protein-like fluorescence augments rapidly, which may
      be due to a mass of FDOM realeased by the old or dead cell fragmentation and the
      degradation of bacteria by using non-FDOM. The fluorescent intensity of
      Alexandrium tamarense, Alexandrium mimutum, Prorocentrum donghaiense and
      Prorocentrum micans can reduce at anaphase of decadency phase because of the
      degradation of bacteria and light. The same genus of algae can produce similar
      FDOM, for example: Alexandrium tamarense, and Alexandrinum mimutum, Prorocentrum
      donghaiense and Prorocentrum micans, but the positions of the fluorescence peaks
      are different.

PMID- 18720818
TI  - [Study on the interaction of luteolin with human serum albumin by fluorescence
      quenching method].
AB  - The interaction between luteolin and human serum albumin (HSA) was studied by
      using fluorescence quenching spectra, synchronous fluorescence spectra and ultra
      violet spectra. The results showed that luteolin had a strong ability to quench
      the fluorescence of HAS The Stern-Volmer curve of the fluorescence quenching of
      HSA by luteolin indicated that the mechanism behind the quenching between
      luteolin and HSA was a static quenching. According to the Forster theory of non
      radiation energy transfer, the binding distances (r) and the binding constants
      (KA) were calculated. The thermodynamic parameters showed that the interaction
      between luteolin and HSA was driven mainly by hydrophobic force. Synchronous
      spectra were used to investigate the conformational changes of HSA.

PMID- 18720819
TI  - [Preparation and structural characterization of mixed LB films of TMB * TCNQ and
      stearic acid].
AB  - Mixed LB films of the CT complex of TMB * TCNQ and stearic acid (SA) were
      prepared. The structures, molecular orientation and morphology of the mixed LB
      films were characterized by IR, UV-Vis-NIR, XRD and AFM. Our results show that
      TMB * TCNQ could be deposited on solid substrates by mixing with SA. The complex
      is mixed-stack, and the degree of charge transfer is 0.35. The chromophore planes
      of both TCNQ and TMB are perpendicular to the substrate surface and the
      hydrocarbon chain of SA is inclined at an angle with respect to the substrate
      surface. There are two kinds of diffraction bands in the XRD spectra, and they
      probably arise from SA and TMB * TCNQ, respectively. The morphology of mono- and
      multilayer mixed LB films with molar ratio 1 : 1 consists of many nanorods and
      particles, and the amount of nanorods and particles increase with increasing the
      number of monolayers.

PMID- 18720820
TI  - [Immunoresonance scattering spectral assay for the determination of antithrombin
      III].
AB  - A new sensitive, selective and simple immune resonance scattering spectral assay
      was proposed for the determination of trace amounts of Antithrombin-III (AT-III).
      It was based on the immune reaction of AT-III with the goat-anti-human AT-III
      antibody and the resonance scattering effect of the immunocomplex particles in pH
      7.2 Tris-HCl buffer solution and in the presence of polyethelene glycol
      (PEG)6000. The results showed that the resonance scattering signal of AT-III and
      goat-anti-human AT-III antibody was very weak. However, AT-III was combined with
      goat-anti-human AT-III antibody specifically, and aggregated to form
      immunocomplex particles, which enhanced the resonance scattering intensity
      greatly and produced three resonance scattering peaks at 368 nm, 491 nm and 536
      nm respectively. The strongest resonance scattering peak was at 491 nm. In the
      present paper, the influences of pH, goat-anti-human AT-III antibody and PEG-6000
      concentration, incubation temperature, reactive time, and foreign substances were
      investigated. The result showed that the resonance scattering intensity at 491 nm
      (I(RS)) is linear to the AT-III concentration in the range of 62.5 to 850 ng x
      mL(-1), under the optimum conditions of 0.30 mL goat-anti-human AT-III antibody,
      30 mg x mL(-1) polyethelene glycol-6000, being incubated at 37 degrees C for 15
      min, the voltage at 400 V, and the excitation and emission slit width both at 5.0
      nm. Its regress equation is deltaI(RS) 0.062 5c + 1.36, and a relative
      coefficient of 0.996, with a detection limit of 29.4 ng x mL(-1). The results of
      co-existing substance tolerance test showed that 1.40 x 10(5) ng x mL(-1)
      glycine, 9.0 x 10(3) ng x mL(-1) L-glutamic acid, 5.0 x 10(5) ng x mL(-1)
      glucose, 5.0 x 10(4) ng x mL(-1) urea, 1.5 x 10(4) ng x mL(-1) IgG, 3.0 x 10(4)
      ng x mL(-1) human serum albumin, and 1.5 x 10(4) ng x mL(-1) bovine serum albumin
      did not interfere with the resonance scattering determination of 2.50 x 10(2) ng
      x mL(-1) AT-III, when the relative error was within +/- 10%. Four polyethelene
      glycols, i. e. polyethelene glycol-4000, polyethelene glycol-6000, polyethelene
      glycol-10000 and polyethelene glycol-20000, on the immune resonance scattering
      spectral system were examined in details. The results show that polyethelene
      glycol-6000 has low blank and high deltaI(RS) value, and was chosen for use. The
      new resonance scattering spectral method features high sensitivity, good
      selectivity, simplicity and rapidity, and was applied to the quantitative
      analysis of AT-III in plasma and serum samples with satisfactory results. Its
      recovery is in the range of 90.2%-108.9%.

PMID- 18720821
TI  - [Study and application of determination of protein with meso-tetra-(3,5-dibromo-4
      hydroxyphenyl) porphyrin fading spectrophotometry].
AB  - In the present paper, the binding characteristics and spectral behavior of
      interaction of meso-tetra-(3, 5-dibromo-4-hydroxyphenyl) porphyrin [T(DBHP)P] as
      a new-style probe with protein were studied by the techniques of
      spectrophotometry. The experiment showed that Tween-80 microemulsion was
      efficiently used to enhance the sensibility and stability of the system at pH 4.
      17(Britton-Robinson buffer solution). Under optimum conditions, the
      characteristics of absorption spectral of meso-tetra-(3,5-dibromo-4
      hydroxyphenyl) porphyrin-protein were investigated, the maximum absorption was
      located at 425 nm, and the reducing value of absorbance A was in proportion to
      the concentration of proteins in the range 0.50-6.00 microg x mL(-1) for bovine
      serum albumin, 0.05-0.60 microg x mL(-1) for ovalbumin, and the limits of
      detection were 0.106 microg x mL(-1) for bovine serum albumin and 0.039 microg x
      mL(-1) for ovalbumin. The experiments indicated that the proposed method featured
      high sensitivity and good selectivity and stability, and was simple and
      relatively free from interference of coexistent substances. It has been applied
      to the determination of protein in milk samples with satisfactory. The recovery
      for the investigated protein from milk was 99.56%-100.2% and the relative
      standard deviations were less than 2.2%. The sensitive method for the
      quantitative determination of proteins was proposed and may be applicable to the
      determination of ultra amounts of protein in food analysis. The effect of ionic
      strength on the system was investigated, and the result indicated that the
      binding force between meso-tetra-(3, 5-dibromo-4-hydroxyphenyl) porphyrin and
      protein was judged as electrostatic force. The influence of protein denaturation
      was also studied, under higher temperature the structure of protein was
      destroyed, and thermodynamic movement of the molecular of protein was intensified
      as the heating time extended.

PMID- 18720822
TI  - [Comparison of 51 element contents in normal human lung tissue over twenty
      years].
AB  - Changes in content and distribution of elements in human tissues may reflect
      changes in environmental backgrounds, and are closely related to human health. To
      investigate the change in element background in normal lung tissue in different
      stage, we used ICP-MS, ICP-AES and GFAAS to determine 51 element contents in
      normal human lung samples of 1982-83 year (n = 7) and compare with those of 2004
      05 year (n = 16). Samples were from healthy male adults who died suddenly, and
      were treated with microwave digestion and wet digestion method. The results show
      that the contents of 23 elements (Na, Mg, P, K, As, Mo, Ag, Ba, Bi, Y, La, Ce,
      Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu) are significantly higher, and 6
      elements (Zn, Ga, Ge, Se, Au and Zr) are significantly lower in the 2004-05
      samples than those in the 1982-83 samples. This difference would be related to
      the changes in environmental backgrounds and people's living habit during twenty
      years. The distinctive decrease in contents of the 2004-05 samples for most
      measured rare earth elements (REEs) may be due to more rational usage of REEs in
      present, while were the soil and corps were largely abused in 1980s in China. The
      significant increase in contents of some useful micro-elements (Zn and Se ) in
      the present samples maybe because of the increased intake of these elements as
      people own more health consciousness. Besides, the increased contents of heavy
      metal Pb, Cd, Cr and Ni in the present samples may be related to the
      deterioration of air quality as industrialization course. More than half of
      measured elements have been significantly changed over twenty years, indicating
      that some normal value ranges of element contents should be adjusted according to
      the difference.

PMID- 18720823
TI  - [Simultaneous determination of trace elements in mistletoe by ICP-AES].
AB  - A method for the simultaneous determination of elements Cu, Mg, Zn, Mn, Ni, Se,
      K, Na, Ca and Fe in mistletoe after HNO3-H2O2 digestion by ICP-AES was studied.
      The recoveries obtained by standard addition method were between 90.8% and
      112.8%, while the RSD (n = 5) was in the range of 0.47%-4.59%. The results showed
      that there were rich K, Ca, Mg and Na in the mistletoe, and offered scientific
      data for the ulterior study on mistletoe.

PMID- 18720824
TI  - [Estimation of soil organic matter and soil total nitrogen based on NIR
      spectroscopy and BP neural network].
AB  - Estimation models of soil organic matter (SOM) and soil total nitrogen (TN) were
      established based on NIR spectroscopy and BP neural network A total of 150 soil
      samples were collected from the tested farm, and the NIR spectra of all soil
      samples were measured. First, data pretreatment was performed for each sample
      with the method of locally weighted scatter plot smooth filtering. Then the box
      plot analysis for the measured SOM data and TN data were conducted separately and
      the information about the shape, location, and distribution of the target data
      was obtained. The variance between the SOM data was very small, and most of them
      were concentrated on the median. This was also observed from TN data. Thus
      clustering analysis was carried out for the target parameters of the soil samples
      so that the original dataset with 150 spectra was clustered to 50 groups. For
      each group, the average of spectral data was calculated at every wavelength to
      obtain a new spectrum. The new spectrum was calculated with natural logarithm and
      normalized, which was taken as a new sample. Principal component analysis (PCA)
      was executed for 50 new samples and the principal components with over 99.98% of
      cumulative proportion of correlation matrix were extracted to establish BP neural
      network. According to the analysis result of SOM content, the calibration
      accuracy of the model was 0.999, and the validation accuracy reached to 0.854.
      According to the analysis result of the soil TN content, the calibration accuracy
      of the model was close to 1, and the validation accuracy reached 0.808. The
      result shows that the smooth filter can weaken the noise in the data, expose the
      data features, provide a reasonable starting approach for parametric fitting; and
      improve the prediction accuracy; It is feasible and practical to estimate soil
      parameters by using BP neural network with the prediction accuracy of 0.854 (SOM)
      and 0.808 (TN); Compared to the other prediction modeling method, the BP neural
      network model has higher robustness and better fault tolerance, and the model
      accuracy would not be affected by the several outline samples when the number of
      samples is large enough.

PMID- 18720825
TI  - [Determination of trace elements in traditional Chinese medicine from Changbai
      Mountain by ICP-MS].
AB  - The effects of different digestives for the fritillaria and atractylodes were
      compared. Many trace elements in the planted and wild fritillaria and
      atractylodes were determined by ICP-MS The results show that the RSD and recovery
      are better if the planted and wild fritillaria and atractylodes were digested
      with HNO3-H2O2. Among the many elements determined from the fritillaria and
      atractylodes, Cu, Zn, Fe, Mg and Mn are the dominant chemicals. The content of Fe
      was higher in the wild fritillaria and atractylodes than that in the planted
      fritillaria and atractylodes, while the contents of heavy metal Pb and Cd were
      lower in the wild fritillaria and atractylodes than those in the planted
      fritillaria and atractylodes. The wild fritillaria and atractylodes contain Co,
      which was not determined in the planted fritillaria and atractylodes. The
      experimental results showed that the detection limits were lower than 0.086 ng x
      g(-1) with low RSD(n = 7, 4.85%) for most metal chemicals determined, and the
      standard recoveries (n = 7) ranged from 96.8 to 103.4%.

PMID- 18720826
TI  - [Determination of mineral elements in different part of Astragalus
      membranaceus(Fisch.) by FAAS].
AB  - Having digested the root and shoot of Astragalus membranaceus (Fisch.) with the
      mixture of nitric acid and perchloride acid (4 : 1) under the condition of the
      bolling point and the normal pressure, the contents of the five mineral elements
      necessary to humanity, potassium, copper, zinc, iron and manganese in root and
      shoot of Astragalus membranaceus (Fisch.) were determined by flame atomic
      absorption spectroscopy (FAAS), and the results were analyzed in statistics. The
      correlative coefficient of the standard curve in this method is 0.997 3-0.999 9,
      the recovery of standard addition was 92.88%-109.25% and the relative standard
      deviation (RSD, n = 5) was 0.393 5%-3.175 2%. The method is simple and the
      results were accurate and reliable. The contents of K, Fe, Zn, Mn, Cu in the root
      and shoot of Astragalus membranaceus (Fisch.) were compared. The results showed
      that the sequence of the content of metal elements is as follows in all samples:
      K > Fe > Zn > Mn > Cu. However, the distribution of elements in shoot and root is
      not uniform, and the content of Fe, Zn and Cu in root is richer than in shoot.
      There are abundant Fe, Zn and Cu in root, for example, the content of Fe in root
      is 1.54 times that in shoot. In addition, there are also abundant mineral
      elements in the shoot, especially in K and Mn, for example, the content of K in
      shoot is 1.63 times that in root. The contents of K, Fe, Zn, Mn and Cu in shoot
      are in agreement with the medical effects of Astragalus membranaceus (Fisch.).
      The results should provide useful data for investigating the distribution of
      mineral element in Astragalus membranaceu body and the correlation between the
      mineral element content and the effect of medicine in Astragalus membranaceus
      (Fisch.).

PMID- 18720827
TI  - [Determination of trace elements of Gentiana macrophlla and Gentiana straminea by
      microwave digestion-FAAS].
AB  - An acid-assisted microwave digestion procedure is optimized for the determination
      of trace elements in traditional Chinese medicine by the use of flame atomic
      absorption spectrometric (FAAS) techniques. Microwave-assisted digestion has the
      advantages of reduced time for sample dissolution, fewer possibilities for
      technical errors caused by spilling of hot digestion solutions, use of less
      chemicals, and lower losses of volatile metals. In addition, modern microwave
      ovens are safer and simpler and provide more controlled and reproducible
      conditions than hot plate or block digesters. Flame atomic absorption
      spectrometry (FAAS) is more commonly applied techniques in the de termination of
      trace elements. The accurate measurement of trace elements concentrations in
      samples of traditional Chinese medicine is an important goal in research for
      medical effects of traditional Chinese medicine. The purpose of this study was to
      determine the contents of the trace elements in Gentiana macrophlla and Gentiana
      straminea. In order to identify the accuracy of the procedure, the operating
      conditions was selected before the determination of trace elements. In order to
      gauge the effectiveness of digestion, the selection of digestion conditions of
      the technique was undertaken. The results showed HNO3-H2O2 (5 : 1) as a microwave
      digestion agent with suitable temperature and time was optimum choice in the
      digestion procedure. Analysis limits were also selected according to the low
      detection limits and the good precision. They were Fe(248.3 nm), Mn (279.5 nm),
      Ni (232.0 nm), Cu(324. 8 nm), Zn (2.139 nm), Ca (422.7 nm), Mg (285.2 nm) and Cr
      (357.9 nm), respectively. The working curves were obtained by using multi
      elemental standard solutions and line relation was good. Under the selected
      conditions, the contents of trace elements Fe, Mn, Ni, Cu, Zn, Ca, Mg and Cr in
      Gentiana macrophlla and Gentiana straminea were directly determined using working
      curve methods. The relative standard deviations (RSD) and recovery of the method
      have been undertaken to obtain reliable results for trace element determinations.
      The recovery rates obtained by standard addition method were between 88.1%
      114.5%, and the relative standard deviations (RSD) were lower than 3.12% after
      optimization of the operating conditions. These figures showed that the method
      gave good recoveries and accuracy. The analytical results indicated that there
      were comparatively rich elements in Gentiana macrophila and Gentiana straminea,
      such as Ca, Mg, Fe, Mn and Zn, especially the concentration of Ca and Mg.
      However, concentrations of Ni and Cr in Gentiana macrophlla and Gentiana
      straminea were very low, especially the concentration of Ni. The worse value
      obtained for Ni was probably due to its inhomogeneous distribution and very low
      concentration in Gentiana macrophlla and Gentiana straminea. In addition, a
      comparison of the contents of trace elements between Gentiana macrophlla and
      Gentiana straminea indicated that Gentiana macrophlla was rich in the trace
      elements such as Fe, Mn, Ni and Mg, and Gentiana straminea was rich in the trace
      elements such as Zn, Cu, Ca and Cr. The result will provide scientific datas for
      discussing the relationship between the contents of these elements in Gentiana
      macrophlla and Gentiana straminea and the medical effects. Furthermore, our study
      provides new scientific foundation for further study and general application of
      Gentiana macrophlla and Gentiana straminea.

PMID- 18720828
TI  - [Recent development of speciation analysis for trace arsenic].
AB  - The present paper summarizes recent development in the measurements of trace
      arsenic element, including six aspects such as spectrophotometry, atomic
      adsorption spectrometry, hydride generation atomic fluorescence spectrometry,
      inductively coupled plasma-atomic emission spectroscopy, X-ray fluorescence
      spectrometry, united detection of chromatography-atomic characteristic and so on.
      The basic characteristics and application fields of each method are introduced.
      The advantages and disadvantages of different methods are discussed. It is
      pointed out that great progress has been made for the measurements of trace
      arsenic element in the past decades, but studies on speciation analysis of trace
      arsenic are still limited. For various speciation of trace arsenic in nature, how
      to find and develop various efficient, selective separation and analysis
      technologies is one of the most important problems to be considered. More
      attention should be paid to the united application of different modern analysis
      technologies for trace arsenic.

PMID- 18720829
TI  - [Study on the cultural relic material site and period by EDXRF].
AB  - With the development of the element analysis technology, the energy-dispersive X
      ray fluorescence (EDXRF) technique is now well established as a powerful tool for
      qualitative and quantitative elements analyses when studying on the cultural
      relic materials. Being characteristic of quick and non-destructive analysis,
      involving high-precision, a wide concentration range, easy sample preparation,
      good reproducibility and synchronously analyzing the elements from Na(Z11) to
      U(Z92), this technique is appropriate for analyzing precious ancient ceramics. In
      the present study, the major, minor and trace elements compositions of 6 samples
      from Guan kiln in the southern song dynasty, 6 samples from Longquan kiln in the
      Southern Song dynasty and 2 modern imitations were analyzed by EDXRF. The results
      prove further that the raw materials in Hangzhou and Longquan are different and
      stable, and show that EDXRF is a successful and feasible method for identifying
      the provenance and dynasty an ancient ceramic originated from.

PMID- 18720830
TI  - [A study on image processing of digital radiography and measure of material micro
      density directly].
AB  - Due to the high influents of the device itself and the surrounding environment,
      the background brightness of the digital radiography image is uniform and the
      image shows big noise. Therefore, in order to identify digital radiography images
      precisely, a further image processing is necessary. In this study, adaptive
      filtering, histogram equalization techniques and difference image methods were
      used for image processing and the results show that these techniques were useful
      to denoise, to intensify brightness and to rectify the background. In order to
      verify the feasibility of these techniques, poplar wood samples of heterogeneous
      material were used as experimental materials and Micro-density was measured
      directly by applying the linear relationship between grey scale of DR image and
      penetrate material density and contrasted with the result of microdensitometer.
      The results show these techniques were feasible and even gave a more precise
      measurement on wood micro-density compared to microdensitometer.

PMID- 18720831
TI  - [Research on the fourth generation of Saposhnikovia divaricata by XRF].
AB  - To cultivate oriented new varieties, Saposhnikovia divaricata seeds were carried
      by Shenzhou "3" satellite and filtered when they were being brought back. In the
      present paper, X-ray fluorescence(XRF) was used to mensurate and analyze the
      contents of elements of the two samples from the ground group and the 4th
      generation of space Saposhnikovia divaricata (space group) that have advantages
      in branches and leaves and yields. The contents of the main mineral elements in
      the two samples are the same basically. But the contents of the elements Zn, Fe,
      Mn and Cu from the outer group are higher than the ground group. Especially the
      contents of Zn, Fe, Mn and Cu concerning the curative effect in the space group
      increase 4.39, 1.23, 0.84 and 0.9 times as compared to the ground group. In the
      space group the contents and proportions of the mineral elements are improved and
      optimized. XRF method can be used for overall element analysis of and research on
      Chinese herbal medicines. Space flight breeding is an effective method for the
      selection of new Saposhnikovia divaricata breed.

PMID- 18720832
TI  - [Mapping metal elements of Shuangbai dinosaur fossil by synchrotron X-ray
      fluorescence microprobe].
AB  - The metal elements mapping of Shuangbai dinosaur fossil, was obtained by
      synchrotron x-ray fluorescence (SXRF). Eight elements, Ca, Mn, Fe, Cu, Zn, As, Y
      and Sr were determined. Elements As and Y were detected for the first time in the
      dinosaur fossil. The data indicated that metal elements are asymmetrical on
      fossil section. This is different from common minerals. Mapping metals showed
      that metal element As is few. The dinosaur most likely belongs to natural death.
      This is different from Zigong dinosaurs which were found dead from poisoning.
      This method has been used to find that metals Fe and Mn are accrete, and the same
      is ture for Sr and Y. This study indicated that colloid granule Fe and Mn, as
      well as Sr and Y had opposite electric charges in lithification process of
      fossils. By this analysis, compound forms can be ascertained. Synchrotron light
      source x-ray fluorescence is a complementary method that shows mapping of metal
      elements at the dinosaur fossil, and is rapid, exact and intuitionist. This study
      shows that dinosaur fossil mineral imaging has a potential in reconstructing the
      paleoenvironment and ancient geology.

PMID- 18720833
TI  - [Phylogenetic analysis of the 16S rRNA and HSP60 gene sequences of the morphology
      based taxa of myxobacteria].
AB  - OBJECTIVE: Using the 16S rRNA or HSP60 gene sequences to identify the
      myxobacteria taxa at the levels of species and genus, which were difficult to be
      classified by their morphological characteristics. METHODS: 15 myxobacterial
      strains were isolated using the traditional isolation methods, and classified
      based on their morphological characteristics. The 16S rRNA and HSP60 gene
      sequences were amplified by PCR methods, and phylogenetically analyzed. RESULTS:
      Eleven strains possessed typical morphological characteristics, while the other
      four strains 0085-4, 0121-3, NM03 and Myx9736 were degenerated of fruiting body
      structures in different extents. The strains were classified into the suborder
      Cystobacterineae, located in three genera of two families based on their
      morphological characteristics. The 16S rRNA gene sequences were 95.4% to 99.5%
      homology, which were in good consistence with the classification of the
      morphology-based genera; while the HSP60 gene sequences were in longer
      phylogenetic distances. CONCLUSION: The present morphology-based classification
      of myxobacteria is highly consistent with the phylogenetic results of 16S rRNA
      gene sequences at the levels of genera or higher taxa; while HSP60 gene sequences
      provides a more efficient method for identification of closely related
      myxobacteria species.

PMID- 18720834
TI  - [A molecular view of microbial diversity in sediment of the Jinshan hot spring,
      Guangdong province].
AB  - OBJECTIVE: The aim of this study is to analyze the microbial diversity in the
      sediment of Jingshan hot spring. METHOD: We extracted environment DNA from the
      sediment and then amplified the 16S rRNA genes of prokarotype and internal
      transcribed spacers (ITS) DNA of eukarotype by PCR with specific conservative
      primers. The PCR products were ligated to the T vectors and transformed into
      Escherichia coli to construct libraries. The libraries were analyzed by amplified
      ribosomal DNA restriction analysis (ARDRA) approach. The clones of dominant ARDRA
      patterns were selected to sequence. The sequence similarities were analyzed by
      using the BLAST programs for searching the GenBank DNA databases. RESULTS: We
      identified 14 dominant operational taxonomic units (OTUs) from prokarotype G.
      group. The Phylogenetic tree shows that 7 of them (JS-GU20, JS-GU1, JS-G37, JS
      G29, JS-GM2, JS-G42, JS-G41) belong to Bdellovibrio. They had the highest
      similarity to Bacteriovorax sp. NE1 (EF092445) and Bdellovibrio sp. JS5
      (AF084859), 96% and 99% respectively. Four major OTUs of prokarotype X group
      belong to Cyanobacterium. One of them, named JS-X2, has a similarity of 95% with
      an uncultured Cyanobacterium (L35331) which was gained from a hot spring of the
      Yellowstone National Park and has a similarity of 89% with Thermosynechococcus
      elongatus BP-1 (47118315). Most OTUs of eukaryotic group have 90% sequences
      similarity to that of Penicillium sp.. CONCLUSION: The results showed that the
      microbial diversity in the sediment of Jinshan hot spring is rich. And the result
      of several clones' similarity to Bacteriovorax sp. showed that there might be a
      new group of thermophilicBacteriovorax sp. in the hot spring sediment.

PMID- 18720835
TI  - [Diversity and phylogeny of rhizobia isolated from root nodules of Sesbania
      cannabina in Jinshajiang arid river valley].
AB  - OBJECTIVE: To study the diversity and phylogeny of Rhizobia strains from Sesbania
      cannabina in Jinshajiang arid river valley in Sichuan province, China. METHODS:
      We used numerical taxonomy, 16S rDNA PCR-Restriction fragment length
      polymorphism(RFLP), sequences analysis of 16S rDNA and Glutamine synthetaseII(GS
      II)genes. RESULTS: Based on the dendrograms generated from numerical taxonomy,
      the strains were clustered into 6 groups at the similarity of 93%. Four groups
      were closely related to type strains of R .tropici, R.etli, S. saheli, A .rubi
      respectively, and two groups were separated with type strains. The results of 16S
      rDNA PCR-RFLP were in good agreement with that of numerical taxonomy, only two
      separated groups showed some differences. SCAU176 and SCAU144 representing the
      strains of two separated groups were selected for sequence analysis .The results
      of 16S rDNA sequence indicated that SCAU176 and SCAU144 were related to type
      strains R. huautlense, and the homology coefficient with R. huautlense was 100%
      and 98.9% respectively. GS II sequence analysis revealed that SCAU176 and SCAU144
      were clustered together, and the homology coefficient with the nearest type
      strains R. tropici was below 90%. CONCLUSION: Rhizobia of Sesbania cannabina in
      Jinshajiang arid river valley are highly diverse, they are closely related to
      Rhizobium, Sinorhizobium and Agrobacterium.

PMID- 18720836
TI  - [Effect of Cry1Ca7 protein modified by site-directed mutagenesis on inhibiting
      Spodoptera exigua Hubner].
AB  - OBJECTIVE: To obtain the mutants with different toxicity from the wild-type
      CrylCa7. METHODS: Insecticidal crystal protein CrylCa7 from Bacillus
      thuringiensis which is highly toxic to Spodoptera exigua, an important
      agricultural pest in China, and we mutated this toxin by over-lapping extensive
      PCR method in different domains to obtain 11 chimeric mutants. RESULTS: The
      results of bioassays against Spodoptera exigua neonates showed that several
      conserved amino acid sites were crucial to insects. The pesticidal activities of
      most of mutated proteins were decreased, including Glycinel38 Serine,
      Threonine221 Aspartic acid, Threonine221 Argine, Asparagine251 Serine,
      439GlycineGlycineThreonine440, Asparagine306 Argine, Tryp-tophan376
      Phenylalanine, Argine522 Glutamic acid and Argine570 Glycine. The activity of
      those mutated proteins in the Domain II was 439GlycineGlycineThreonine440 <
      Asparagine306 Argine < Tryptophan376 Phenylalanine. In the Domain III, the mutant
      Argine522 Glutamic acid < Argine 570 Glycine, their toxicities reduced distinctly
      compared with CrylCa7. The toxicities of the mutant Argine148 Glycine in Domain I
      increased six-fold, nevertheless the activities of the mutants Glycine138 Serine,
      Threonine221 Argine and Asparagine251 Serine mutant reduced totally, even the
      mutant of Threonine221 Aspartic acid was not toxic entirely. CONCLUSION: It is
      relatively easier to obtain mutant with higher toxicity in Domain I of CrylCa7
      protein than these in both DomainII and III. We can use the improved mutant genes
      as the potential resources to construct novel engineering bacteria and transgenic
      plant, meanwhile, to perform the study of interaction mechanism between insects
      and Cry proteins.

PMID- 18720837
TI  - [Isolation, prokaryotic expression and activity analysis of thymidylate kinase
      (tmk) gene from Phytoplasma of wheat blue dwarf].
AB  - OBJECTIVE: Wheat blue dwarf (WBD) is an important disease in winter wheat
      district, which causes serious losses in wheat production. Thymidylate kinase
      (TMK) catalyses the phosphorylation of dTMP to dTDP in the de novo and salvage
      pathways of dTTP synthesis in both prokaryotes and eukaryotes. In order
      effectively control this phytoplasma, we isolated the thymidylate kinase gene of
      WBD phytoplasma, and analyzed the catalytic activity of TMK protein. METHODS: tmk
      gene was amplified from the phytoplasma of WBD, the amplicons were digested with
      EcoR I and Hind III and then inserted into expression vector pET-30a(+). The
      polyHis-tagged TMK was expressed in E. coli BL21 (DE3) and fusion protein was
      obtained and purified by Ni-NTA column. The TMK activities were measured by the
      method of en-zyme-coupled assay involving Mg2+, dTMP and ATP. RESULTS: Two genes,
      tmk-1 and tmk-2 were obtained, with the molecular weight of 630 bp and 624 bp.
      Both of them encoded an amino acid sequence with three conserved functional
      motifs which related with binding NTP/NMP. The fusion protein, TMK-2 had a higher
      catalytic activity (112.41 U/mg) than TMK-1 (16.4 U/mg), and its optimum
      catalytic conditions were 32 degrees C, pH7.3, 1.5 mmol/L Mg2+ and 1 mmol/L ATP.
      CONCLUSION: TMK-1 and TMK-2 had conserved functional motifs in their primary
      sequence, and suggested that they may function as TMK enzymes. But, the TMK-1
      polyHis fusion protein had very low catalytic activity, the possible reason was
      that two highly conserved regions were absent in TMK-1, and it might function as
      another type of kinase in WBD phytoplasma. This experiment lay a foundation for
      further study of the TMK function in infection and reproduction of WBD
      phytoplasma.

PMID- 18720838
TI  - [Virulence changes of H5N1 avian influenza virus after gene reassortment].
AB  - OBJECTIVE: Recently H5N1 subtype avian influenza virus (AIV) is capable of
      mortality to aquatic bird. The molecular basis for the virulence of this virus is
      still poorly understood. METHODS: We characterized two H5N1 subtype viruses,
      A/mallard/Huadong/Y/2003 (Y) is nonpathogenic to mallard whereas
      A/mallard/Huadong/S/2005 (S) is highly pathogenic to mallard. Using reverse
      genetics, we constructed a series of single-gene or multiple-gene reassortants
      from these two viruses. RESULTS: Substitution of single-gene for PB2, PB1, PA
      (3P), HA and of combination for 3P gene resulted in complete attenuation of S
      virus in mallard. However, these corresponding substitutions only slightly
      increased virulence of Y virus in mallard. Other gene segments had little
      contribution to the virulence of both viruses. CONCLUSION: These results indicate
      that the pathogenicity of H5N1 AIV to mallard was regulated by multiple gene
      segments, and these regulations had more sensitive effect on highly pathogenic
      virus backbone than on low pathogenic virus backbone.

PMID- 18720839
TI  - Isolation and identification of an alkaliphilic Bacillus flexus XJU-3 and
      analysis of its alkaline amylase.
AB  - OBJECTIVE: To isolate and identify a new Bacillus strain capable of growing under
      highly alkaline conditions as alkaline amylase producers and to characterize its
      enzymatic properties. METHODS: The isolates were sampled from alkaline sewage in
      Shihezi city, Xinjiang and screened by plating them on the amylase agar medium
      depending on the halo zone diameter. The alkaline amylase producer with best
      enzymatic activity was designated as XJU-3. XJU-3 was identified by its
      physiological and biochemical characteristics, 16S rDNA sequence homology, and
      the content of its major cellular fatty acids. RESULTS: XJU-3 was a Gram
      positive, spore-forming, aerobic, motile rod alkaliphilic bacterium. It can grow
      at a broad range of pH (4.0-12.5) in Luria broth medium and its optimum growth
      was at pH 10 and 37 degrees C. Its NaCl tolerance was up to 15%. Its major
      cellular fatty acids were anteiso-C15:0 and iso-C15:0. Comparative 16S rRNA gene
      sequence analyses showed that XJU-3 was most closely related to Bacillus flexus,
      with 99% similarity. The genomic DNA (G+C) content of our isolate was 39.13 mol
      %. XJU-3 produced extracellular alkaline amylase, and its maximal enzyme activity
      was observed at 40 degrees C and pH 10.0. More than 70% of the enzymatic activity
      was remained at pH 13.0. The enzyme activity was strongly enhanced with the
      presence of Co2+ and Mg2+. CONCLUSION: The strain XJU-3 was confirmed as B.
      flexus. Owing to its excellent pH tolerance, the kinds of major cellular fatty
      acids, and several phenotypic characteristics that were different from the
      description of the reference strain, the strain was further classified as a new
      variant of the species B. flexus. The enzymatic properties of XJU-3 alkaline
      amylase indicated its potential in industrial applications.

PMID- 18720840
TI  - Optimization of kappa-carrageenase production by Pseudoalteromonas sp. AJ5.
AB  - OBJECTIVES: To optimize the culture conditions of Pseudoalteromonas sp. AJ5 for a
      higher production of extracellular kappa-carrageenase. METHODS: A kappa
      carrageenan-degrading bacterium AJ5, capable of utilizing kappa-carrageenan as
      sole source of carbon and energy, was isolated from the intestine of holothurian
      Apostichopus japonicus by enrichment culture technique. The strain was identified
      as the genus Pseudoalteromonas sp. according to its morphological and
      physiological characterization and 16S rRNA gene analysis. Culture conditions for
      the bacterium were standardized for the maximal productivity of the extracellular
      kappa-carrageenase by the single factor and orthogonal tests. RESULTS: According
      to the single factor test, the optimal culture conditions were: 75 mL medium in
      250 mL Erlenmeyer flask, shaking speed of 150 r/min, inoculum's volume 7%, and pH
      8.0. Based on the single factor and orthogonal tests the optimal medium
      components were: kappa-carrageenan (1 g/L), beef extract (2 g/L ), NaCl (20 g/L),
      K2HPO4.3H2O (1 g/L), MgSO4.7H2O (0.5 g/L), MnCl2.4H2O (0.2 g/L), FePO4.4H2O (0.01
      g/L), with the incubation temperature and time of 28 degrees C and 28 h.
      CONCLUSION: Pseudoalteromonas sp. AJ5 secreted an extracellular kappa
      carrageenase. Under the optimal culture conditions, four-fold increase in kappa
      carrageenase activity was achieved as compared to the control.

PMID- 18720841
TI  - [Molecular cloning and heterologous expression of a new xylanase gene from
      Verticillium dahliae].
AB  - OBJECTIVE: Fungus Verticillium dahliae caused greensickness of cotton and
      xylanase is necessary in this pathogenesis. Cloning xylanase gene from V. dahliae
      and heterologous expression might obtain new xylanase. METHODS: By comparing the
      amino acid sequences of over 10 xylanases in 11 families from fungi through
      BLAST, we found 2 highly conserved regions, with a fragment of about 150 amino
      acids coding sequence in between. Degenerate primers complementary to the ends of
      these two conserved regions were designed to amplify the in-between sequence from
      V. dahliae. The whole xylanse gene containing intron was achieved by Genome
      walking PCR method. A 63 bp intron was found through BLAST, the whole cDNA xynG
      was cloned by Dpn I -mediated PCR to delete intron. The cDNA was inserted into
      pHBM905 and expressed in Pichia pastoris GS115, xylanase-secreting transformants
      were selected on plate containing RBB-xylan. The transformant with the largest
      halos was selected for study the character of xylanase. RESULTS: The deduced
      amino acid sequence showed 72% identity with endo-beta-1, 4-xylanase from
      Cochliobolus carbonum and C. sativus in the GenBank, which means xynG is a new
      xylanase gene. The optimal pH of the purified recombinant enzyme was pH6. It
      remains over 50% relative activity at pH5-9. The optimal temperature was 45
      degrees C. The most favorable substrate for the xylanase (XYNG) is Beechwood
      xylan. Mg2+ and Ca2+ improve the enzyme activity by 33.7% and 16.6%,
      respectively. EDTA, beta-Mercaptoethanol and NaN3 don't affect the enzyme
      activity. Tween-80 and DMSO activated enzyme activity by 28.4% and 12.8%. Hg+, in
      concentration of 5 mmol/L, also inhibited the enzyme activity. CONCLUSION: The
      xylanase gene xynG was firstly cloned from the fungi that caused greensickness of
      cotton. The xylanase genes containing one intron can be efficiently cloned from
      plant pathogens and white-rot fungi using strategy in this research. It is
      unnecessary to explore enzyme expression condition and measure enzyme activity of
      the original strain. Enzyme character analysis showed that the XynG have
      potential application in the production of xylo-oligosaccharide and the
      improvement of bread quality.

PMID- 18720842
TI  - [Cultivable microbial diversity at the rhizosphere of Phyllostachys pubescens].
AB  - OBJECTIVE: To obtain the information of the cultivable microbial population
      diversity at the rhizosphere of Phyllostachys pubescens. METHODS: We isolated
      strains from Tianmu Mountain and Jinyun Mountain by diluting plate counting
      method and analyzed the 16S rDNA sequence of the isolates. RESULTS: We obtained
      51 and 31 strains with different morphological character of colonies from Tianmu
      Mountain and Jinyun Mountain separately. The 16S rDNA sequence analysis showed
      that they had similar microbial population diversity. There were 40% and 58%
      firmicutes, 36.7% and 10.52% actinobacteria, 10% and 5.26% alphaproteobacteria,
      10% and 26.32% gammaproteobacteria at the rhizosphere of Phyllostachys pubescens
      from Tianmu Mountain and Jinyun Mountain separately. The dominant bacteria were
      the genera Bacillus in both two areas. CONCLUSION: The result showed that the
      cultivable microbial population diversity was abundant and there were some
      potential novel strains at the rhizosphere of Phyllostachys pubescens. Our
      research made it is possible to further investigate the function of the
      rhizosphere microbes and there interaction with the bamboo plant.

PMID- 18720843
TI  - [Isolation and physiological characteristics of lytic bacteriophages of Vibrio].
AB  - OBJECTIVE: Vibrio is a widely distributed pathogen in aquatic environment. Our
      study aimed at searching for possible biological control of pathogenic vibrio.
      METHODS: We collected natural samples from coast and lakes in spring of 2006 and
      autumn of 2005; and isolated lytic phages by double-layer plate method. We
      identified the hosts with 16S rDNA sequencing and observed their morphology with
      phages under electron microscopy. We also tested the physiological
      characteristics of phages. RESULTS: We isolated 96 bacteria and 2 phages
      (Vibio/XM/P1, Vibio/XM/P2). Their hosts belonged to Vibrio alginolyticus and
      Vibrio anguillarum. Both phages were hexagonal-headed and one with a tail.
      Physiological tests show that their optimum grow condition were pH7, 25 degrees C
      and pH8, 30 degrees C. Both phages were sensitive to high temperature and UV
      light. Vibrio/XM/P2 was sensitive to aether and chloroform whereas Vibrio/XM/P1
      not.

PMID- 18720844
TI  - [Mutagenesis modified of Mx gene from chicken and identification of its antiviral
      specificity].
AB  - OBJECTIVE: To study whether the antiviral specificity of chicken Mx protein is
      determined by an amino acid substitution at position 631. METHODS: We used PCR
      site-directed mutagenesis technique by which a single amino acid was reciprocally
      substituted G with A at position 2032bp of chicken Mx cDNA. Sequence analysis
      confirmed successful mutation from G to A at 2032bp of chicken Mx cDNA. The
      fragments amplified by PCR containing the mutation site were subcloned into a
      enteukaryotic expression vector. Then the recombinant vector was transfected into
      COS-I cell, Mx gene and Mx protein in the transfected COS-I cell were detected by
      RT-PCR and indirect fluorescence assay. RESULTS: The results showed that COS- I
      cell transfected the recombinant plasmid could stably express the Mx protein. The
      antivirus assay showed that Mx protein had characteristics of resistance to
      infection of Newcastle Disease Virus. CONCLUSION: This study may provide a basis
      of the virus-resistant mechanism of Mx protein and production of virus-resistant
      transgenic chicken.

PMID- 18720845
TI  - Prevalence of Shiga toxin- and enterotoxin-producing Escherichia coli in patients
      and animals in Guizhou, China.
AB  - OBJECTIVE: To assess the public health risk, we studied the prevalence of
      enterotoxigenic Escherichia coli (ETEC) and Shiga toxin-producing E. coli (STEC)
      among pig, cattle and human in Guizhou Province. METHODS: E. coli isolates from
      fecal samples were investigated for their virulence markers by polymerase chain
      reaction (PCR) assays. RESULTS: Of 333 E. coli isolates, ETEC was predominant and
      detected in 73 of 112 isolates from patients, 82 of 106 isolates from pigs, and
      18 of 115 isolates from cattle. The distribution of genes st, lt, and st/lt was
      equivalent in ETEC isolates. The detection rate of STEC from pig isolates was
      higher than that from patient and cattle isolates, most of which carried genes
      for st or Lt or both. Furthermore, we analyzed the presence of the fedA gene
      encoding the major subunit of F18 fimbriae in E. coli isolates. Although most
      isolates were negative in the PCR, the presence of F18 fimbriae in the E. coli
      isolates was always associated with enterotoxin genes. In 25 stx-positive STEC
      isolates, however, only 4 STEC from pigs with diarrhea detected fedA.
      CONCLUSIONS: These results indicate that ETEC, coexisting with F18 fimbriae, is
      common in patients, cattle, and pigs, while STEC is dominant in pigs in Guizhou
      Province, China.

PMID- 18720846
TI  - [A flow cytometric assay for the expression of interferon gamma in T lymphocytes
      and its application in the study of EIAV-induced immune response].
AB  - OBJECTIVE: The attenuated vaccine of equine infectious anemia virus (EIAV) is the
      first lentiviral vaccine that provides solid protection against the infection of
      EIAV virulent strains. Study of the immune response induced by EIAV vaccine is an
      important approach to understand the immunity to other lentiviruses. IFN-gamma
      expressed by specifically stimulated lymphocytes is an important indicator for
      the evaluation of T cell-mediated immunity. A flow cytometry based assay was
      established in this study to accurately and effectively detect IFN-gamma
      expression in different subtypes of T lymphocytes in EIAV-infected horses.
      METHODS: Peripheral blood mononuclear cells (PBMC) were prepared from horses
      inoculated with EIAV vaccine stain FDDV (fetal donkey dermal-attenuated virus
      vaccine), virulent strain LV or saline (health control), were stimulated in vitro
      with FDDV or PMA + Inomycin. Brefeldin A was added into the cell culture to block
      protein secretions. Stimulated cells were then labeled with monoclonal antibodies
      specific for equine CD4 and CD8 surface markers, as well as an IFN-gammaspecific
      monoclonal antibody. Flow cytometry was applied to detect CD4+ and CD8+
      lymphocytes expressing IFN-gamma. RESULTS: IFN-gamma positive cell population
      isolated from FDDV-immunized horses was 1.7 +/- 0.9% in CD4+ T cells and 6.1 +/-
      1.2% in CD8+ T cells (n=4). In contrast, only 0.6 +/- 0.1% of IFN-gamma positive
      cells in CD4+ subset and 2.4 +/- 0.9% of IFN-gamma positive cells in CD8+ subset
      of T cells were detected for PBMC isolated from LV-infected horses (n=4).
      CONCLUSION: The multi-fluorescence cell flowmetry detecting both the IFN-gamma
      expressing cells and subsets of T lymphocytes simultaneously, is specific, stable
      and reproducible in evaluating antigen-specific response of IFN-gamma-producing
      lymphocytes. This is an essential approach to study the protective immunity
      induced by EIAV vaccine.

PMID- 18720847
TI  - [Construction of cDNA library of Magnaporthe grisea with magnetic bead].
AB  - OBJECTIVE: We constructed cDNA library of Magnaporthe grisea. The good quality
      cDNA library could facilitate finding proteinaceous elicitors of M. grisea, and
      elucidating the mechanisms of the M. grisea--rice interaction. METHODS: The
      Oligo(dT) combined with the magnetic bead was used to extract mRNA from total RNA
      of Magnaporthe grisea and as primers to synthesize the first-strand cDNA.
      Terminal transferase introduced PolyA into 3'terminal of the first cDNA strand,
      then the PolyA was used for amplifying the second-strand cDNA. Restriction enzyme
      and adapter were avoided in this research, which could solve technical limitation
      of the traditional method. Because all reactions were done in one centrifuge
      tube, this process could reduce the risk of cDNA loss and cross-contamination.
      The primers designed in this research could clone the amplified cDNAs into
      expression vector in a desirable orientation. RESULTS: The cDNA library
      constructed had a high titer of 8.9 x 10(6) cfu/mL, and contained a total clones
      of 8.9 x 10(7) cfu, with an average inserts size of about 1380 bp. CONCLUSION:
      Constructing cDNA library with magnetic bead was a highly efficient method using
      only small amount of experimental materials within a short period.

PMID- 18720848
TI  - [Reconstituting turkey herpesvirus with bacterial artificial chromosome clones].
AB  - Herpesvirus of turkey (HVT) is an alpherpesvirus and widely used as a live
      vaccine against Marek's disease (MD) because of its antigenic relationship with
      Marek's disease virus (MDV). OBJECTIVE: The aim of this study was to construct
      Herpesvirus of turkey Fc126 strain as an infectious bacterial artificial
      chromosome (BAC). METHODS: Using the selection marker Eco-gpt (Xanthine-guanine
      phosphoribosyl transferase)(1.3 kb) and BAC vector pBeloBAC11(7.4 kb), we
      constructed the transfer plasmid pGAB-gpt-BAC11. Then, the transfer plasmid and
      HVT-infected cells' total DNA were cotransfected into primary chicken embryo
      fibroblasts (CEFs). After six rounds of selection in medium containing
      mycophenolic acid, xanthine and hypoxanthine, we obtained purified recombinant
      viruses. Genomic DNA was extracted and electroporated into Escherichia coli DH10B
      competent cells. BAC clones were identified by restriction enzyme digestion and
      PCR analysis, and then tested for infectivity after transfection into CEFs using
      calcium phosphate. RESULTS: We obtained 25 BAC clones, and reconstituted
      recombinant viruses by transfection of HVT-BAC6 DNA, HVT-BAC8 DNA and HVT-BAC10
      DNA into CEFs respectively. CONCLUSION: In this study, we cloned the complete
      genome of HVT Fc126 strain as an infectious bacterial artificial chromosome.

PMID- 18720849
TI  - [Optimization of plantaricin production by Lactobacillus plantarum ZJ316].
AB  - OBJECTIVE: To enhance the production of plantaricin by Lactobacillus plantarum
      ZJ316 isolated from infant feces. METHODS: We analyzed fermentation parameters
      influencing cell growth and plantaricin production with different medium
      composition and under different cultivation conditions. RESULTS: MRS (DE MAN,
      ROGOSA, SHARPE) medium was more suitable for producing bacteriocin than other
      media. The maximum plantaricin production was obtained in modified MRS medium
      containing 10 g/L maltose and 10 g/L glucose, 10 g/L yeast extract, 10 g/L
      tryptone and 2g/L tri-ammonium citrate, 1 mL/L Tween80, 6 g/L K2HPO4.3H2O, 5 g/L
      sodium acetate, 0.2 g/L magnesium sulfate and 0.05 g/L manganese sulfate. The
      optimal initial pH and temperature for plantaricin production were 6.5 and 30
      degrees C for 24 h. CONCLUSION: After optimizing, the production of plantaricin
      was increased 2.3-fold using the optimized medium, compared with in the basic MRS
      medium.

PMID- 18720850
TI  - [Isolation and characterization of a new glyphosate-resistant strain from
      extremely polluted environment].
AB  - OBJECTIVE: To isolate and characterize a glyphosate-resistant strain from
      extremely polluted environment. METHODS: A glyphosate-resistant strain was
      isolated from extremely polluted soil taking glyphosate as the selection
      pressure. Its glyphosate resistance, growth optimal pH and antibiotic sensitivity
      were detected. Its morphology, cultural characteristics, physiological and
      biochemical properties, chemotaxonomy and 16S rDNA sequences were studied. Based
      on these results, the strain was identified according to the ninth edition of
      Bergey's manual of determinative bacteriology. RESULTS: The isolate was named
      SL06500. It could grow in M9 minimal medium containing up to 500 mmol/L
      glyphosate. The cell growth optimal pH of SL06500 was 4.0. It was resistant to
      ampicillin, kanamycin, tetracycline and chloromycetin. The 16S rDNA of SL06500
      was amplified by PCR and sequenced. Compared with the published nucleotide
      sequence of 16S rDNA in NCBI (National Center for Biotechnology Information),
      SL06500 showed high identity with Achromobacter and Alcaligenes. Based on
      morphological, physiological and biochemical characteristics, the strain was
      identified as Alcaligenes xylosoxidans subsp.xylosoxidans SL06500 according to
      the ninth edition of Bergey's manual of determinative bacteriology. CONCLUSION:
      Strain SL06500 is worthy to be studied because of its high glyphosate resistance.

PMID- 18720851
TI  - [Green fluorescent protein labeling of ylyA gene in Bacillus subtilis].
AB  - OBJECTIVE: In this study we labeled the ylyA gene of Bacillus subtilis with green
      fluorescent protein (GFP) to investigate the subcellular localization of YlyA
      protein. METHODS: Chromosomal DNA was prepared from different strains of Bacillus
      subtilis, ylyA amplified by PCR and the products sequenced. Full-length ylyA was
      then amplified and inserted into the GFP plasmid vector pSG1729, to give pNG426
      containing a gfpmut1-ylyA fusion. Finally, Bacillus subtilis 168 was transformed
      with pNG426, resulting in insertion of the gfpmut1-ylyA fusion into the
      chromosome at the amyE locus. Double crossover integrants (subsequently named
      BS363) were identified by their inability to hydrolyse starch and verified by
      colony-PCR. Following induction of gfpmut1-ylyA expression with 0.5% xylose,
      localization of the fusion protein was determined by epifluorescence microscopy.
      RESULTS: The correct sequence and translation start site of ylyA was identified
      from sequence analysis of the several amplified PCR products permitting
      construction of a gfpmut1-ylyA fusion. Microscopic observation of strain BS363
      showed that the GFP labeled YlyA was distributed around the cell periphery,
      closely juxtaposed with the cytoplasmic membrane. CONCLUSION: GFP labeled YlyA
      produced by BS363 cultured on the nutrient agar solid medium distributed around
      the cell periphery.This suggests it may play a role in membrane biology.

PMID- 18720852
TI  - [Morphological comparison of rabies viral particles before and after rejuvenation
      in suckling mice and morphogenesis of the rejuvenated virus in cells].
AB  - OBJECTIVE: To observe the morphological recovery of rabies virus strain SRV 9
      after rejuvenation in suckling mice and to study its morphogenesis in BHK-21
      cells. METHODS: The long freeze-preserved rabies virus strain SRV 9 was
      rejuvenated through intracerebral inoculation of sucking mice twice, followed by
      propagation in BHK-21 cells. After cell culture the virus was purified through
      sucrose gradient density ultracentrifugation. RESULTS: Electromicroscopy of the
      purified virus showed that effective recovery of viral shape was obtained after
      the rejuvenation with majority of viral particles having a typical bullet-like
      shape and intact spikes on viral membrane. The proportion of DI particles (with
      short triangle and irregular shapes) in rejuvenatd virus supernatant was
      significantly decreased compared to un-rejuvenated virus. Viral morphogenesis in
      cells showed that typical virus particles could form in intracytoplasm 24 hours
      p.i. and the number of matured viral particles in cytoplasm increased
      significantly as culture was prolonged from 24 hours to 96 hours p.i..
      Furthermore, the rejuvenated virus was observed budding from vacuole membrane in
      different patterns. CONCLUSION: (1) The proportion of DI particles can be
      significantly decreased by rejuvenated through intracerebral inoculation of
      sucking mice.(2) The optimal harvest opportunity of SRV9 is after being 1-2
      undiluted passaged. (3) This research provided more information about
      morphogenesis of rabies virus.

PMID- 18720853
TI  - [The regulation of sigmaB activity and its role in some gram-positive food-borne
      pathogens--a review].
AB  - The alternative sigma factor sigmaB modulates the stress response of several Gram
      positive bacteria. Not only does sigmaB play a prominent role in sporulation in
      the Gram-positive model organism Bacillus subtilis, but it also contributes both
      directly and indirectly to bacterial virulence in the food-borne human pathogens
      Bacillus cereus, Listeria monocytogenes and Staphylococcus aureus. As sigmaB has
      been shown to regulate expression of both virulence and virulence-associated
      genes, it indicates that sigmaB is a key player in pathogen ecophysiology.

PMID- 18720854
TI  - [Structure and function of lipopolysaccharide lipid A in bacteria--a review].
AB  - Lipid A, the hydrophobic group of lipopolysaccharide, covers the surface of most
      Gram-negative bacteria. Lipopolysaccharide, known as endotoxin, can cause fatal
      disease like sepsis syndrome. Recent studies have shown that it is only the lipid
      A part of lipopolysaccharide that has the function of endotoxin. After entering
      the human body, lipid A on the surface of bacteria can stimulate the Toll-like
      receptor 4 on the surface of host cells, cause a series of reaction, and produce
      different cytokines. Here we have discussed the structure, biosynthesis and
      pathogenesis of lipid A. The application of lipid A in vaccine development was
      proposed.

PMID- 18720855
TI  - [Authentication of Pinellia pedatisecta and their adulterants by AS-PCR].
AB  - OBJECTIVE: To establish a molecular method for the authentication of Pinellia
      pedatisecta and its adulterants. METHOD: DNA sequences of some species from P.
      tenore, Typhonium and Arisaema were downloaded from GenBank, the sequences were
      aligned using DNAMAN. Allele-specific primers for P. pedatisecta and P. tenore
      were designed according to their SNPs in rpl 20 sequence. The designed primers
      were used to amplify 10 samples of P. pedatisecta, P. ternata and T.
      flagelliforme. RESULT: A 351 bp band was amplified from P. pedatisecta but not
      form P. ternata and T. flagelliforme by primer Pprpl149F and Pprpl484R. A 630 bp
      band was amplified from P. ternate and P. pedatisecta but not from T.
      flagelliforme by primer Ptrpl94F and Ptrpl699R. CONCLUSION: AS-PCR has the
      advantages of highly specific and good reproducibility, by which P. pedatisecta
      can be identified from part of its adulterants quickly. It is a potential method
      to be used in the molecular identification of other materia medica.

PMID- 18720856
TI  - [Microscopical study of original plant of Chinese drug "Dragon's Blood" Dracaena
      cochinchinensis and distribution and constituents detection of its resin].
AB  - OBJECTIVE: To study the anatomy of Dracaena cochinchinensis systematically, and
      find out the distribution and detect the constituents of its resin, in order to
      provide substantial foundation for the formation mechanism of its red resin.
      METHOD: The microscopic structures of D. cochinchinensis were systematically
      observed by using color micrographics, including stem with and without resin,
      roots, barks and leaves. The HPLC fingerprints of the stem with and without resin
      were compared. RESULT: Characteristics of the tangentical longitudinal section of
      stem with resin and surface view of leaves were elucidated. Besides xylem vessels
      and fibers of the stem, it was found that the red resin also exists in the cortex
      parenchyma cells of the stem and the medulla and xylem of the root. According to
      the HPLC fingerprint analysis result of the stems with and without resin, a
      number of flavones and stilbenoids were detected in the stem in which resin
      appeared after it wounded. CONCLUSION: No secretory tissue to secrete resin was
      found in D. cochinchinensis, further study is needed to elucidate the formation
      mechanism of its resin.

PMID- 18720857
TI  - [Study on growth law of Glycyrrhiza uralensis under different planting density].
AB  - OBJECTIVE: To study the growth of Glycyrrhiza uralensis under different planting
      density for providing theoretic evidence for reasonable planting density. METHOD:
      The field experiment was designed by single factor randomized block. RESULT: The
      plant height, root diameter, main root length and branches of main stem were all
      decreased with increasing planting density of G. uralensis. Meanwhile, dry matter
      accumulation on root, leaf, aerial part and rhizome were all decreased with
      increasing planting density. CONCLUSION: Two hundred and seventy thousand
      plants/hm2 was feasible planting density.

PMID- 18720858
TI  - [Genetic diversity evaluation of ex-situ conservation population of Phellodendron
      amurense detected by AFLP markers].
AB  - OBJECTIVE: To evaluate the genetic diversity from ex-situ conservation population
      of Phellodendron amurense. METHOD: Genetic diversity in 67 individuals from ex
      situ conservation population of P. amurense were assessed using AFLP technique by
      eight fluorescent labeled primer groups. RESULT: The eight primer combinations
      generated a total of 1,574 bands, of which 1,354 were polymorphic. As for P.
      amurense at species level, the percentage of polymorphic loci (PPL) was 86.02,
      the effective number of alleles per locus (Ne) was 1.4275 ,the Nei's gene
      diversity (H) was 0.2312, and the Shannon's information index (I) was 0.3973. At
      the population level, the estimates PPL=41.55, H=0.1400, Ne=0.2376 and I=0.2113.
      CONCLUSION: The effect of present ex-situ conservation was preliminarily
      assessed.

PMID- 18720859
TI  - [Research of seed quality grading of Glycyrrhiza uralensis].
AB  - OBJECTIVE: To formulate the seed quality grading standard of Glycyrrhiza
      uralensis. METHOD: Thousand-grain weight, seed moisture, germination rate, purity
      of G. uralensis seed samples from 24 regions were tested. Through statistical
      analysis, the key indicator and the reference indicators for seed quality grading
      were defined. RESULT: Germination percentage was the primary indicator of seed
      quality grading, thousand-grain weight, cleanliness and moisture content were
      important reference indicators. CONCLUSION: The seed quality of each grade should
      reach the following requirements: for first grade seeds, germination percentage >
      or = 85% , purity > or = 92%, thousand-grain weight > or = 13 g, seed moisture <
      or = 11%; for second grade seeds, germination percentage 75%-85%, purity 83%-92%,
      thousand-grain weight 11-13 g, seed moisture < or = 11%; for third grade seeds,
      germination percentage 65%-75%, purity 74%-83%, thousand-grain weight 9-11 g,
      seed moisture < or = 11%.

PMID- 18720860
TI  - [Effect of several penetration enharcers on transdermal permeation and skin
      accumulation of artemether].
AB  - OBJECTIVE: To investigate penetration characteristics of artemether and the
      effect of different permeation enhancer on transdermal permeation of artemether
      through rat skin. METHOD: The permeation experiments were performed using rat
      skin on modified Franz diffusion cells in vitro. The concentrations of artemether
      in receptor compartment at specified time points were determined by HPLC. RESULT:
      The permeating ratio through human skin of artemether solution was Js (2.78 +/-
      0.78) microg x cm(-2) x h(-1), the quantity of drug penetrated through and
      accumulated in the skin by the end of the experiment were (69.07 +/- 3.01) microg
      x cm(-2), (58.93 +/- 3.56) microg x cm(-2) respectively. Four different
      permeation enhancers can improve the transdermal permeation of artemether.
      CONCLUSION: Artemether have the potential to be developed to new transdermal
      preparation.

PMID- 18720861
TI  - [Separation and purification of flavonoids from Smilax glabra by macroporous
      adsorption resin].
AB  - OBJECTIVE: To investigate the process of separating and purifying flavonoids from
      Smilax glabra. METHOD: With the yield of flavonoids as index, the optimum process
      of separating and purifying flavonoids from S. glabra Roxb was screened by static
      and dynamic adsorption tests. RESULT: The static saturated adsorption capacity of
      D101 macroporous resin to flavonoids of S. glabra was 45.6 mg x g(-1) (dry
      resin). The optimum conditions of dynamic adsorption and elution were as that the
      pH, the concentration, the adsorption velocity of the extracting solution, and
      the adsorption capacity were 6.00 +/- 0.20, 4.2 mg x mL(-1), 2 mL x min(-1) and
      15 mL, respectively. The adsorbed resin column was washed by 100 mL 60% ethanol
      with pH value of 8.00 +/- 0.20 at the eluting velocity of 3 mL x min(-1) after
      washed by 100 mL distilled water. CONCLUSION: The flavonoids of S. glabra was
      able to be easily separated and purified by D101 macroporous resin under the
      optimum conditions above, and the recovery rate was higher than 90%. The content
      of obtained flavonoids reached 62.6%, which was 2 times of the content before
      purification.

PMID- 18720862
TI  - [Comparative studies on contents of iridoid in processed products from Gardenia
      jasminoides].
AB  - OBJECTIVE: To compare the contents of iridoid in the different processed products
      from Gardenia jasminoides. METHOD: Contents of geniposide and genipin
      gentiobioside in products were determined simultaneously by HPLC. A kromasil C18
      column at 35 degrees C was used with the acetonitrile-0.3% formic acid anhydrous
      (12:88) as the mobile phrase. The detection wavelength was set at 238 nm and the
      flow rate was 1.0 mL x min(-1). RESULT: The obtained linearity of the two
      components was good with that the relative coefficients (r) were over 0.9994 and
      the average recoveries were 101.8%, 99.1%, respectively. CONCLUSION: The method
      is simple, accurate with good reproducibility. The results showed contents of two
      components are difference in the different processed products.

PMID- 18720863
TI  - [Separation and purification process of total flavones and total tannins from
      Apocynum venetum leaves with macroreticular resin].
AB  - OBJECTIVE: To investigate the purification process of total flavones and total
      tannins from Apocynum venetum leaves with macroreticular resin. METHOD: The
      static capacity absorption, dynamic absorption ratio and dynamic elution ratio of
      different types of macroreticular resins were studied and compared in order to
      find the best one among the eight macroreticular resins, and the technical
      process of the type of HPD-400 type macroreticular resin was studied in detail.
      RESULT: The type of HPD-400 type macroreticular resin showed the best
      comprehensive absorption property with the following technological conditions:
      the current velocity was 1 BV x h(-1), the volume of distilled water was 2 BV,
      the eluting reagent was 60% ethanol, and the volume of 60% ethanol was 3 BV.
      CONCLUSION: The purity of total flavones and total tannins in the product is up
      to 80% after purified with HPD-400 macroreticular resin. Therefore, this
      purification process is feasible.

PMID- 18720864
TI  - [Neocaesalpin L1, a new diterpenoid compound from Caesalpinia minax].
AB  - OBJECTIVE: To study the chemical constituents of Caesalpinia minax. METHOD: The
      chemical constituent was isolated by various chromatographic metheds and its
      structure was elucidated by the analysis of spectral data and physiochemical
      properties. RESULT: One diterpenoid compound was isolated from the 95% ethanolic
      extract of C. minax, and identified as 12alpha -methoxyl-14beta-hydroxy-lalpha,
      6alpha, 7beta-triacetoxycass-13 (15)-en-16, 12-olide. CONCLUSION: Neocaesalpin L1
      was a new compound and named as neocaesalpin L1.

PMID- 18720865
TI  - [Studies on chemical constituents from herbs of Taraxacum mongolicum].
AB  - OBJECTIVE: To investigate the chemical constituents of the herbs of Taraxacum
      mongolicum. METHOD: The chemical constituents were isolated by various column
      chromatographic methods and their structures elucidated mainly by NMR and MS
      evidences. RESULT: Forty-four components were obtained and identified were as
      artemetin (1), quercetin (2), quercetin-3', 4', 7-trime-thyl ether (3), luteolin
      (4), luteolin-7-O-beta-D-glucopyranoside (5), luteolin-7-O-beta-D
      galactopyranoside (6), genkwanin (7), isoetin (8), hesperetin (9), genkwanin-4'-O
      beta-D-lutinoside (10), hesperidin (11), quercetin-7-O-[beta-D-glucopyranosyl (1-
      >6) -beta-D-glucopyranoside (12), quercetin-3, 7-O-beta-D-diglucopyranoside (13),
      isoetin-7-O-beta-D-glucopyranosyl- 2'-O-alpha-L-arabinopyranoside (14), isoetin-7
      O-beta-D-glucopyranosyl-2'-O-alpha-D-glucopyranoside (15), isoetin-7- O-beta-D
      glucopyranosyl-2'-O-beta-D-xyloypyranoside (16), caffeic acid (17), furulic acid
      (18), 3-O-caffeoylquinic acid (19), 3, 5-di-O-caffeoylquinic acid (20), 3, 4-di-O
      caffeoylquinic acid (21), 4, 5-di-O-caffeoylquinic acid (22), 1-hydroxymethyl-5
      hydroxy-phenyl-2-O-beta-D-glucopyranoside (23), p-hydroxybenzoic acid (24), p
      coumaric acid (25), 3, 5-dihydroxylbenzoic acid (26), gallic acid (27), gallicin
      (28), syringic acid (29), 3, 4-dihydroxybenzoic acid (30), caffeic acid ethyl
      ester (31), esculetin (32), rufescidride (33), mongolicumin A [6, 9, 10
      trihydroxy-benzoxanthene-1, 2-dicarboxylic acid] (34), mongolicumin B [1 l
      hydroxy-2-oxo-guaia-1 (10), 3, 5-trien-8, 12-lactone] (35), isodonsesquitin A
      (36), taraxacin (37), sesquiterpene ketolactone (38), taraxasteryl acetate (39),
      phi-taraxasteryl acetate (40) and lupenol acetate (41), palmitic acid (42), beta
      sitosterol (43), and stigmasterol (44). CONCLUSION: Four compounds (14, 15, 34
      and 35) were new compounds, compounds 1, 3, 6-13, 20-22, 30 and 31 were isolated
      from this genus for the first time, while compounds 18, 23-29, 32 and 37-42 were
      obtained from this species for the first time.

PMID- 18720866
TI  - [Comparative investigation of the components in rats plasma before and after
      orally administrating Shuanghuanglian injection].
AB  - OBJECTIVE: To investigate the main constituents absorbed in the blood after
      orally administrating Shuanghuanglian injection extracts of its composed crude
      drug and provide the foundation for optimizing the prescription of
      Shuanghuanglian powder for injection. METHOD: Through analysing HPLC fingerprint
      established based on shuanghuanglian powder for injection and extracts of it
      composed crude drug, the active investigation were carried out among the peaks of
      control plasma and plasma containing drug in rats, shuanghuanglian powder for
      injection and extract of its composed crude drug. And the analysis was performed
      about relative content of constituents in each sample. Furthermore their original
      drugs and the metabolites in plasma containing drug were ascertained. RESULT:
      Eight compounds were detected in plasma after oral administration of
      Shuanghuanglian, four of them were the original compounds contained in
      Shuanghuanglian powder for injection and three of them were relative metabolites.
      It has also found that contents of original compounds such as baicalin and
      chlorogenic acid fell off gradually, but their metabolites increased in rat
      plasma in vivo. With increasing time the main components of forsythia have not
      been detected obviously in rats plasma. CONCLUSION: In some extent, the compounds
      absorbed into blood from Shuanghuanglian powder for injection and their
      metabolites are the effective constituents, and its plasma pharmacochemistry
      should be subject to illuminate the pharmacological effects and the active
      mechanism.

PMID- 18720867
TI  - [Effects of chemical constituent in roots of Achyranthes Bidentata].
AB  - The difference of ingredients between the roots from the SP1 plants of
      Achyranthes Bidentata carried by satellite and the control's were evaluated in
      this study. The techniques of ultraviolet-visible spectroscopy (UVS), infrared
      spectroscopy (IR), Xray diffraction (XRD) and SDS-PAGE were used to analyse the
      chemical constituent in the root of A. bidentata. The results demonstrated that
      the UVS, IR, XRD and protein fingerprints of the roots from A. bidentata were
      distinct with special characters. The difference of the IR, XRD and protein
      fingerprints could be discriminated the satellite plants roots from those of the
      control, however, there were no difference of the UVS fingerprints between the
      satellite plants roots and the control. This indicated that the kinds of chemical
      ingredients were not different between the two groups, but the contents of some
      chemical ingredients deceased in SP1 plants of A. bidentata carried by satellite.

PMID- 18720868
TI  - [Absorption mechanism of icariin across Caco-2 monolayer model].
AB  - OBJECTIVE: To study the absorption mechanism of icariin by using Caco-2 monolayer
      model. METHOD: Caco-2 cell monolayer model was used to study the bi-direction
      transport of icariin. The effects of time, drug concentration and inhibitor on
      the absorption of icariin were studied. The concentration of icariin in cell
      culture medium was measured by UPLC and the apparent permeability coefficients
      (Papp) was calculated. RESULT: The amount of icariin which was transported
      increased linearly with the time (14 hr). The ratio of PBA/PAB was larger than 4.
      Verapamil, the P-glycoprotein inhibitor, could cause significantly effect on
      transport of icariin, PAB increased, the ratio of PBA/PAB decreased. CONCLUSION:
      The reason for low absorption of icariin in Caco-2 cell model may be the
      secretion of the P-gp transporter.

PMID- 18720869
TI  - [Determination of vitexin-rhamnoside in Beagle dog plasma and preliminary
      pharmacokinetics of Yixintong sustained release tablets].
AB  - OBJECTIVE: To develop an HPLC method to determine vitexin-rhamnoside in plasma of
      Beagle dogs and study the pharmacokinetics and bioavailability of Yixintong
      sustained release tablets in Beagle dogs. METHOD: A newly-developed HPLC method
      using C18 column and methanol-acetonitrile-tetrahydrogenfuran-0.5% acetic acid
      (1:1:19.4:78.6) as mobile phase was validated, and then was employed to determine
      vitexin-rhamnoside in plasma of Beagle dogs after oral administration of
      Yixintong sustained release tablets and general tablets. The main pharmacokinetic
      parameters were estimated by pharmacokinetic program 3p87. The non-compartmental
      pharmacokinetic parameters were also calculated on basis of the statistic moment
      theory. RESULT: The pharmacokinetic profiles of Yixintong sustained release
      tablets and the general tablets were fitted to a one-and two-compartment open
      model, respectively. The T1/2, Tmax, AUC0-infinity and MRT for Yixintong
      sustained release tablets were 5.22 h, 4.0 h, 6,792.75 ng x h x mL(-1) and 8.4 h,
      respectively, compared with 8.94 h, 1.0 h, 5,880.4 ng x h x mL(-1) and 6.1 h for
      the general tablets. The relative bioavailability of the Yixintong sustained
      release tablets was 115.5% in Beagle dogs. CONCLUSION: The sustained-release
      characteristic of Yixintong sustained release tablets were confirmed by
      pharmacokinetic study.

PMID- 18720870
TI  - [Study of Fufang Haishe capsule against cell apoptosis].
AB  - OBJECTIVE: To study mechanismt of Fufang Haishe capsule for dementia by observing
      the effect of it on PC-12 cell apoptosis, which was induced by beta-amyloid
      protein (Abl-42). METHOD: Nerve growth factor (NGF) was used to cultivate the PC
      12 cells. Fufang Haishe capsule at different concentrations was added into the
      culture medium so as to identify the nontoxic concentrations with MTT. To analyze
      the PC-12 cell apoptosis respectively by MTT assay, Flow cytometry (FCM
      technique) with different concentrations of Fufang Haishe capsule (0.01, 0.1, 1,
      5 mg x mL(-1)), adding Ab or not Western blot was used to detect apoptosis which
      was measured on the implementation of caspase-9 and caspase-3 activity. RESULT:
      Fufang Haishe capsule could significantly inhibit the apoptosis of PC-12 cells
      induced by Abeta with increased colorimetric MTT asay ( compare among the control
      group and concentration 0, 0.01, 0.1, 1 and 5 mg x mL(-1) group, which is the
      same below: 1.75 +/- 0.12, 0.73 +/- 0.35, 0.79 +/- 0.11, 0.83 +/- 0.07, 1.31 +/-
      0.07, 1.80 +/- 0.38, P < 0.01) and the decreased apoptosis rate of the cells
      which was analysed by flow cytometry (1.93 +/- 0.41)%, (46.17 +/- 4.08)%, (35.35
      +/- 4.63)%, (28.62 +/- 3.81)%, (15.13 +/- 3.15)%, (7.84 +/- 1.76)%, P < 0.01. In
      addition, Fufang Haishe capsule inhibited the activity of caspase-9 and caspase-3
      of PC-12 cells which was induced by Abeta. CONCLUSION: Fufang Haishe capsule
      significantly inhibite apoptosis of PC-12 cells induced by Abeta. The mechanism
      might be that Fufang Haishe capsule decrease the activity of the apoptosis
      implementing protein,caspase-9 and caspase-3.

PMID- 18720871
TI  - [Effects of matrine on oncogenicity of H22 cells modified by TIM2 gene in vivo].
AB  - OBJECTIVE: To investigate the effects of matrine on the anti-tumor efficiency of
      H22 murine hepatocarcinoma cell-based vaccine modified by TIM2 gene in vivo.
      METHOD: The combinant eukaryotic expression vector pIRES2-EGFP-TIM2 was
      constructed and transfected into H22 cells by lipofectamin. The monoclone of the
      positive H22-TIM2 cells and negative control H22-EGFP cells were selected by G418
      pressure and limited dilution method in turn. The H22 whole-cell-based vaccine
      were inoculated to establish the tumor-bearing mouse model, and its oncogenicity
      and immunogenicity were observed in vivo. Then the matrine was administered to
      the tumor-bearing mice inoculated by H22-TIM2 cells, H22-EGFP cells and H22
      cells, and the inhibitory effect of matrine on tumor was studied. RESULT: The co
      expression of EGFP protein and TIM2 mRNA were detected in H22-TIM2 cells. The
      rate of tumor formation in mice injected of H22-TIM2 cells was 41%, lower than
      that of H22 cells and H22-EGFP cells injection (92%) in mice. The growth of tumor
      were significantly inhibited vaccinated with H22-TIM2 cells in mice. The
      inhibitory rate of tumor (IR) was 69.2% in mice of H22-TIM2 group, higher than
      that of mice treated with matrine and H22 cells injection, the later was 67.5%.
      Matrine could dramatically strengthen the anti-tumor efficiency of H22 cells
      modified by TIM2 gene, with the highest tumor inhibitory rate (IR) (90.6%) in all
      the experimental mice. The spleen index, populations of CD4-positive lymphocytes
      and the ratio of CD4-positive to CD8-positive lymphocytes of spleen in mice
      vaccinated of H22-TIM2 cells were obviously higher than those in the other
      groups. CONCLUSION: The oncogenicity of H22 cells is markedly impaired after
      modified by TIM2 gene. Matrine can strengthen the inhibitory effect of H22-TIM2
      cells on tumor in mice. These data give us important clues to further study the
      biological role of TIM2 gene in tumor immunity and explore the molecular
      mechanism of matrine in suppressing tumor.

PMID- 18720872
TI  - [Influence of Zea mays L. saponin (ZMLS) on ultrastructure of kidney and pancreas
      in diabetes rats induced by streptozocin].
AB  - OBJECTIVE: To discuss the effect of Zea mays L. saponin (ZMLS) on ultrastructure
      of kidney and pancreas in the diabetes rats induced by streptozocin. METHOD: The
      diabetic rat model was established by injections of STZ, blood glucose, the
      ultrastructure of the kidney and pancreas were observed. RESULT: Compared with
      the model group, the large, middle-dose ZMLS groups and melbinum group could
      remarkably decrease the blood glucose (P < 0.01), the large, middle, small-dose
      ZMLS groups could remarkably prevent the pancreatic islet beta-cell from the
      injury induced by Streptozotocin. Melbinum and the large, middle-dose ZMLS groups
      could remarkably increase mitochondrial Vv, deltam and euchromatin Vv (P < 0.01),
      and significantly decrease the delta, Nucleus delta and heterochromatin Vv (P <
      0.01). The small dose of ZMLS obviously increases mitochondrial Vv (P < 0.05).
      CONCLUSION: ZMLS showed good effect on decreasing blood glucose and protection
      action on the kidney and pancreas injury of induced by STZ.

PMID- 18720873
TI  - [Effect of Qingxin Kaiqiao fang on learning and memory ability and morphology of
      hippocampal nerve cells in AD mice].
AB  - OBJECTIVE: To study the effect of the Qingxin Kaiqiao fang on learning and memory
      ability and shape hippocampal nerve cells in Alzheimer disease (AD). METHOD: One
      handred and fifty mice were divid into five groups: blank group, model group, two
      groups of treatment by Qingxin Kaiqiao fang (14.82, 7.41 g x kg(-1)), piracetan
      comparison group (0.42 g x kg(-1)). The model group was orally given AlCl3 (200
      mg x kg(-1)) every day. For Qingxin Kaiqiaofang and piracetan groups, AlCl3
      treatment was given for 6 days at the beginning, followed by giving orally AlCl3
      in the morning and drug in the afternoon for 8 weeks. Then, learning and memory
      aility, the contents of nitric oxide (NO), NO synthase (NOS) and
      acetylcholinesterase (AchE) in brain, and morphology of hippocampal nerve cells
      were investigated. RESULT: Learning and memory ability of Qingxin Kaiqiaofang
      groups was improved, compared with comparison group; the difference was
      significant (P < 0.05, P < 0.01). The drug could prevent hippocampal nerve cells
      from damaged obviously. The contents of NO, NOS and AchE in mice of treatment
      groups were lower than those of comparison group; the difference was significant
      (P < 0.05, P < 0.01). CONCLUSION: Qingxin Kaiqiaofang can improve learning and
      memory ability of AD mice, prote chippocampal nerve cells, and treat Alzheimer
      disease.

PMID- 18720874
TI  - [Effect of Xinnao Shutong capsule on apoptosis after cerebral ischemia and
      reperfusion in rats].
AB  - OBJECTIVE: To study apoptosis-regulating cytokines and apoptosis on focal
      cerebral ischemia and reperfusion in rats treated with Xinnao Shutong capsule.
      METHOD: Rat models of focal cerebral ischemia and reperfusion were established by
      thread ligation in middle cerebral artery occlusions (MCAO). After 24 hours, the
      brains were removed to detect changes of protein expression of Bax, Bcl-2, Fas,
      Fas-L and caspase-3 by immuno-hisochemistry, and apoptosis of cortical neurons by
      TUNEL RESULT: Compared to control, brain cortex have decreasing the protein
      expression of Bcl-2 and the ratio of Bcl-2/Bax, increasing the protein expression
      of Bax, Fas, Fas-L and caspase-3 of ischemia and reperfusion models group (P <
      0.01). Xinnao Shutong capsule group could increase the protein expression of Bcl
      2 and the ratio of Bcl-2/Bax, and obviously decrease the protein expression of
      Bax, Fas, Fas-L and caspase-3, then reduce the number of apoptotic cells of
      cortex (P < 0.01). CONCLUSION: Xinnao Shutong capsule protect injured rat brain
      tissue, may be related to decrease neuronal apoptosis and adjusted protein
      expression of apoptosis-regulating cytokines.

PMID- 18720875
TI  - [Comparision study pharmacokinetics of different source cinnamon acid].
AB  - OBJECTIVE: To study relatively pharmacological activities of cinnamon acid in
      blood serum of rabbit administered cinnamon acid, cinnamon and Jingui Shenqi
      pills. METHOD: RP-HPLC determine and analysis blood serum sample from rabbits
      administered cinnamon acid, cinnamon and Jingui Shenqi pills. Condition of colour
      spectrum was Symmetry C18 (3.9 mm x 150 mm, 5 microm) chromato bar, mobile phase
      was methanol-1% glacial acetic acid water-solution (45:55), flow rate was 0.8 mL
      x min(-1), temperature of bar was 35 degrees C, detection wave length was 285 nm.
      The serum pharmacokinetic parameters were calculated with 3p87. RESULT: Linear
      range of cinnamon acid is from 0.06-15 microg x mL(-1) (r = 0.9997), the lowest
      detectability is 0.054 microg x mL(-1). Pharmacokinetic process of cinnamon acid
      in rabbit could be all fitted to two-compartment model. CONCLUSION: Sensitive and
      exclusive HPLC that adopt can exactly detect serum concentration in rabbits
      administerd cinnamon acid. Pharmacokinetic parameters of three conditions can
      reveal pharmacokinetics regularity of cinnamon acid in rabbit.

PMID- 18720876
TI  - [Protective effects of Shexiang Xingnaonin on focal cerebral ischemia/reperfusion
      injury and mechanism].
AB  - OBJECTIVE: To study the protective effects of Shexiang Xingnaonin (SXN) on focal
      cerebral ischemia/reperfusion injury and its mechanism. METHOD: Middle cerebral
      artery occlusion (MCAO) was used to make focal cerebral ischemia/reperfusion
      model by in travascular nylon filament occlusion. The protective effects of SXN
      at different doses were evaluated by investigating neurological function score,
      pathomorphology of brain, the ultrastructure of neuron, expression of tumor
      necrosis factor-alpha, thrombogenesis in vitro, platelet aggregation and lysing
      effect of blood clot in vitro. RESULT: Compared with model group, SXN (0.08, 0.16
      g x kg(-1)) could decrease the neurological score, improve pathomorphology and
      neuron ultrastructure of brain, inhibit the expression of TNF-alpha, decrease the
      length, wet weight and dry weight of thromb and inhibit platelet aggregation. And
      SXN (0.16, 0.32 g x L(-1)) could dissolve blood clot in vitro. CONCLUSION: SXN
      has protective effects on focal cerebral ischemia/reperfusion injury. The role of
      inhibit the expression of TNF-alpha, inhibit thrombogenesis and platelet
      aggregation might contribute to its neuroprotective effects.

PMID- 18720877
TI  - [Explore new clinical application of Huanglian and corresponding compound
      prescriptions from their traditional use].
AB  - Huanglian is a commonly used Chinese medicinal herb in the ancient and the
      present. It has a history of 2000 years in clinical application, having the
      efficacy of "Clear away heat and remove dampness, purge the sthenic fire and
      eliminate toxic materials", therefore can be used for various diseases or
      syndromes in types of dampness-heat and fire-toxin by internal or external use.
      Compound prescriptions mainly based on Huanglian or prescribed by Huanglian, such
      as Puji Xiaodu Yin, Huanglian Jiedu Tang, Zhusha Anshen Wan, Qingying Tang,
      Angong Niuhuang Wan, Niuhuang Qingxin Wan, Jiaotai Wan, Huanglian Ejiao Tang,
      Zuojin Wan, Danggui Longhui Wan, Huanglian Yanggan Wan, Wu Xiexin Tang, Lianpu
      Yin, Gegen Huangqin Huanglian Tang, Baitouweng Tang, Xianglian Wan etc. All of
      these are well-known formulas for clearing away toxin of heat-fire of heart and
      liver, as well as dampness-heat of stomach and intestines. Nowadays, Huanglian is
      generally considered as a kind of antibiotic and antivirus herb and is widely
      used for many infective diseases. In fact, it is also used to cure cardiovascular
      and cerebrovascular diseases, diabetes and cancer based on pharmacological
      studies. Having been using Huanglian in treating the above diseases and having
      conducted clinical and experimental research on cancer and liver diseases, the
      author observed that Huanglian and its compound prescriptions have obvious
      effects on liver diseases such as acute or chronic hepatitis, liver fibrosis,
      liver cirrhosis and liver cancer due to types of dampness-heat and fire-toxin.
      Part of the effects has been proved by experimental research and it is worth
      carrying out more research in this area for development and clinical application.

PMID- 18720878
TI  - [Textual research of medicinal and edible plants in Shanhaijing].
AB  - OBJECTIVE: To investigate the purification process of total flavones and total
      tannins from Apocynum venetum leaves with macroreticular resin. METHOD: The
      static capacity absorption, dynamic absorption ratio and dynamic elution ratio of
      different types of macroreticular resins were studied and compared in order to
      find the best one among the eight macroreticular resins, and the technical
      process of the type of HPD-400 type macroreticular resin was studied in detail.
      RESULT: The type of HPD-400 type macroreticular resin showed the best
      comprehensive absorption property with the following technological conditions:
      the current velocity was 1 BV x h(-1), the volume of distilled water was 2 BV,
      the eluting reagent was 60% ethanol, and the volume of 60% ethanol was 3 BV.
      CONCLUSION: The purity of total flavones and total tannins in the product is up
      to 80% after purified with HPD-400 macroreticular resin. Therefore, this
      purification process is feasible.

PMID- 18720879
TI  - [Comparative evaluation of over-under myringoplasty and underlay myringoplasty
      for repairing tympanic membrane perforation].
AB  - OBJECTIVE: To evaluate the effect of over-under myringoplasty technique on
      repairing tympanic membrane perforation regarding with the rate of perforation
      closure, the frequency of postoperative complications occurrence and the level of
      hearing improvement. METHOD: In this retrospective study, a total of 74 patients
      (77 ears) underwent myringoplasty and had been followed up for over 6 months,
      which was performed by means of the underlay technique in 44 patients (45 ears)
      and over-under technique in 30 patients (32 ears) from Jan 2002 to Jan 2007. In
      the underlay group, the grafted membrane was placed medial to the remaining drum
      and the manubrium of the malleus. In the over-under group, the grafted membrane
      was placed under the remaining drum and over the malleus. Comparatively evaluate
      the effect of the underlay technique and that of the over-underlay technique on
      repairing tympanic membrane perforation. RESULT: The rate of perforation closure
      and hearing improvement in the underlay group of 45 ears was 89.0% and 57.5%
      respectively, while that in the over-under group of 32 ears were 87.5% and 71.9%
      respectively. The air-bone gap decreased by 4.9 dB in the underlay group, while
      it decreased by 9.7 dB in over-under group. After more than 6 months of following
      up, the frequency of postoperative atelectasis of the underlay group and the over
      under group was 17.8% and 6.25% respectively. Meanwhile, the frequency of
      postoperative reperforation of these two groups was 5.9% and 6.25% respectively.
      Blunting of the anterior angle of the tympanic membrane occurred in 3 ears in the
      over-under group. Lateralization of the graft was not observed in either group.
      CONCLUSION: Over-under technique could reduce the occurrence of the adhesions
      between the grafted membrane and promontorium tympani by placing the grafted
      membrane between the remaining drum and the malleus. Furthermore, the level of
      hearing improvement in over-under group was higher than that in underlay group.
      Over-under myringoplasty is a more effective technique as comparison to underlay
      myringoplasty for repairing middle to large tympanic membrane perforations.

PMID- 18720880
TI  - [Influence of childhood obstructive sleep apnea-hypopnea syndrome on hearing].
AB  - OBJECTIVE: To explore the influence of hypoxemia on the hearing of children with
      childhood obstructive sleep apnea-hypopnea syndrome (OSAHS). METHOD: Auditory
      brainstem response (ABR) and distortion-product otoacoustic emission (DPOAE) was
      recorded in 68 ears and 60 ears respectively of children suffering from OSAHS
      with "A" tympanogram. Meanwhile, ABR and DPOAE was also recorded in 30 controls
      of children with "A" tympanogram. RESULT: There was no statistical difference
      between the mild OSAHS group and the control group in the latency of wave I, III
      and V, the interval between wave I and III, III and V, I and V. There was
      significant difference between the moderate and severe OSAHS group and the
      control group in the delayed latency of wave I. There was significant difference
      between the mild OSAHS group and the control group in the amplitudes of DPOAE at
      8 kHz. There was significant difference between the moderate and severe OSAHS
      group and the control group in the amplitudes of DPOAE at 6 kHz and 8 kHz.
      CONCLUSION: Cochlear function was affected when AHI > or = 10/h. ABR and DPOAE
      could be used to detect the early damagement of auditory function in childhood
      OSAHS.

PMID- 18720881
TI  - [The effect of desloratadine on quality of life of patients with seasonal
      allergic rhinitis].
AB  - OBJECTIVE: To assess the effect of desloratadine on quality of life (QOL) in
      patients with seasonal allergic rhinitis. METHOD: A randomized, double-blind,
      placebo-controlled study was designed on fifty patients with seasonal allergic
      rhinitis. The patients were randomly divided into three groups: A group: taking
      desloratadine by mouth and taking spraying of normal sodium; B group: placebo
      group, taking placebo by mouth and taking spraying of normal sodium; C group:
      taking desloratadine by mouth and taking spraying of Nasonex. Rhinitis quality of
      life (RQOL) questionnaire was used to evaluate QOL of patients with seasonal
      allergic rhinitis. The method of taking tabella was one tablet, one time a day;
      the method of taking spraying was one spray each nostril, once a day. The
      investigation lasted for two weeks. The RQOL questionnaire was administered at
      the start of the treatment and after one and two weeks of treatment by the
      telephone follow-up investigation. RESULT: After 1 and 2 weeks of treatment,
      symptoms scores were significantly decreased in the A group and C group compared
      with the placebo group (P < 0.05). After 1 and 2 weeks of treatment by the
      methods of A and C, the QOL of patients with seasonal allergic rhinitis was
      significantly improved compared with placebo group (P < 0.05). There was no QOL
      improvement in the placebo group. CONCLUSION: Desloratadine could decrease
      symptom scores and improve QOL in patients with seasonal allergic rhinitis. The
      RQOL questionnaire could help doctor to effectively evaluate QOL in patients with
      seasonal allergic rhinitis, because of its integrity and convenience.

PMID- 18720883
TI  - [Relationship between otoacoustic emissions and blood-lead levels in school
      children].
AB  - OBJECTIVE: To investigate the relationship between blood levels of lead and the
      function states of cochlear outer hair cells (OHC). METHOD: Two hundred and fifty
      six children lived in Pb-Zn mine area and Yiliang country, aged from 6 to 7 years
      were enrolled in this study. Blood lead (B-Pb) levels were measured. Otoacoustic
      emission (OAE) tests including transient evoked otoacoustic emissions (TEOAE) and
      distortion products otoacoustic emission (DPOAE) were also measured in these
      children. RESULT: The difference in B-Pb levels between the school children who
      lived in mine area and children lived in country was significant (P < 0.01).
      There were negative correlations between the B-Pb levels and the signal to noise
      ratio (SNR) on DPOAE test in children who lived in country and those lived in
      mine area (P < 0.01). The difference in relative coefficients of B-Pb levels
      between the children lived in mine and children lived in country were significant
      (P < 0.01). CONCLUSION: The B-Pb levels of children who lived in mine area were
      higher than that of those lived in country. SNR decreased in plumbism cases. Long
      term Pb expose may influence the function of cochlear OHC and higher B-Pb levels
      may lead to worse function of OHC.

PMID- 18720882
TI  - [Clinical investigation of different routes of administration of dexamethasone on
      sudden deafness].
AB  - OBJECTIVE: To investigate the therapeutic effects of conventional treatment with
      different routes of administration of dexamethasone on sudden deafness. METHOD:
      Eighty-four patients with sudden deafness were included in this prospective
      randomized study. Twenty one patients (group 1) were treated with taking
      dexamethasone orally combined with conventional methods. Another 21 patients
      (group 2) were treated with intravenous dexamethasone injection combined with
      conventional methods. Group 3 (21 patients) were treated with intratympanic
      dexamethasone injection by the way of external ear combined with conventional
      methods. The other 21 patients (group 4) were treated with intratympanic
      dexamethasone injection by the way of pharyngotympanic tube combined with
      conventional methods. The hearing gains at 0.5, 1.0, 2.0, 4.0 kHz and the mean
      values were compared among four groups. RESULTS: The average hearing gains of 1,
      2, 3 and 4 group was 21.3 dB, 27.5 dB, 43.2 dB and 48.1 dB respectively. Group 3
      and group 4 had statistical difference compared with group 1 and group 2 in the
      average hearing gains. There was no obviously statistical difference between
      group 1 and group 2 and between group 3 and group 4. In patients with PTA < or =
      70 dB, the average hearing gains at 0.5, 1.0, 2.0, 4.0 kHz had no obvious
      difference (P > 0.05) among four groups. However, in patients with PTA > 70 dB,
      there was statistical difference between group 1, 2 and group 3, 4 (P < 0.05),
      the hearing gains of group 3. 4 were apparently higher than that of group 1, 2.
      However, there was no significant difference of hearing gains between group 1 and
      group 2 (P > 0.05) and between group 3 and group 4 (P > 0.05). CONCLUSION: The
      conventional drug treatment with taking dexamethasone orally or intravenous
      dexamethasone injection had no obvious effect on sudden deafness with PTA > 70
      dB, but the conventional drug treatment with intratympanic dexamethasone
      injection is a useful treatment for sudden deafness. Comparison with whole body
      administration, intratympanic dexamethasone injection is more convenient to use
      in clinic, and with less prohibitions and complications. Patients with PTA > 70
      dB should take intratympanic dexamethasone injection in early days.

PMID- 18720884
TI  - [Clinical anatomical study of the adult lateral skull base].
AB  - OBJECTIVE: Through the observation and the measurements of the significant
      anatomical landmark the lateral skull base, to provide anatomical data of
      clinical location and navigation for surgery at the lateral skull base. METHOD:
      Significant anatomical landmarks of twenty adult cadaveric heads (40 sides) fixed
      in 10% formaldehyde and 20 operation cases (20 sides) had been observed and
      measured. Lateral skull bases of cadaveric heads were numbered from 1st to 40th,
      while the operation cases were numbered from 1st to 20th. RESULT: The anatomical
      data was achieved by measuring related anatomical landmark as follows: the
      distances between the significant landmark of the lateral skull base and the pars
      neuraxis, vein of the jugular foramen; the areas of trautmann triangle; post
      labyrinths triangle and the superficial triangle of processus mastoideus; the
      maximal distance of initiative displacement of facial nerve in the lateral skull
      base operations. CONCLUSION: The data measured at lateral skull base could
      effectively help operators not only to enlarge the field of vision in operations
      with security and to avoid the damagement of the important blood vessel and
      nerves, but also to retain the function of the facial nerve to the utmost.

PMID- 18720886
TI  - [Low-frequency tympanometry in normal neonates].
AB  - OBJECTIVE: To find the characteristic of tympanogram results obtained from
      normative neonates 2 - 7 days about low frequency (226 Hz) probe tone, and to
      determine the normative values for tympanometric variables. METHOD: Transient
      evoked otoacoustic emission (TEOAE) screening were performed by using AccuScreen
      Pro instrument for 135 neonates. Among them, 105 neonates passed the TEOAE
      screening in both ears. The 226 Hz probe tone tympanograms and their normative
      values were obtained from them using GSI-33 middle ear analyzer. RESULT: The 226
      Hz tympanometric data for the 105 neonates (210 ears) passed the TEOAE screening
      in both ears showed a double-peaked tympanogram in 202 ears (96.19%), a single
      peaked tympanogram in 8 ears (3.81%). For double-peaked tympanogram in 202 ears,
      the tympanometric normative values was below: the first peak admittance is (0.91
      +/- 0.18)mmho, Tpp is about (18.02 +/- 12.26)daPa; the second peak admittance is
      (1.05 +/- 0.23)mmho, Tpp is about (-35.05 +/- 16.80) daPa; the admittance of
      notch between the two peaks is (0.74 +/- 2.57)mmho, its pressure is about (0.37
      +/- 7.61) daPa. Vec is about (0.50 +/- 0.08)ml. CONCLUSION: The 226 Hz
      tympanograms obtained from this cohort may serve as a guide for evaluating middle
      ear function in neonates.

PMID- 18720885
TI  - [Expression and its significance of eosinophil major basic protein in chronic
      rhinosinusitis].
AB  - OBJECTIVE: To evaluate the expression of eosinophil major basic protein (MBP) in
      chronic rhinosinusitis (CRS) and discuss the role of MBP in the pathogenesis in
      CRS. METHOD: Thirty-eight nasal mucus obtained from CRS patients were used to
      detect the expression of MBP by Elisa assay. Thirty nasal mucus samples from
      health people were used as control. RESULT: The expression of MBP of nasal mucus
      obtained from CRS patients was obviously higher than that of nasal mucus obtained
      from control. There was significant statistical difference (P < 0.01).
      CONCLUSION: MBP was involved in the formation of CRS.

PMID- 18720887
TI  - [Expression and clinical significance of E-cadherin and beta-catenin proteins in
      human laryngeal cancer].
AB  - OBJECTIVE: To investigate the roles of E-cadherin and beta-catenin play in the
      carcinogenesis and progression of laryngeal carcinoma. METHOD:
      Immunohistochemistry staining (PicTure two steps method) was used to detect E
      cadherin and beta-catenin proteins expression in laryngeal carcinomas and normal
      epithelia around tumors. RESULT: In 60 laryngeal carcinomas, the abnormal
      expression rates of E-cadherin and beta-catenin were 55.00% and 66.67%
      respectively. The significant relationship was observed between abnormal E
      cadherin and beta-catenin expression and differentiation, clinical stage and
      lymph node metastasis. There was a positive relationship between the expression
      of beta-catenin and E-cadherin in same sample. CONCLUSION: The abnormal
      expression of E-cadherin and beta-catenin were closely related with
      differentiation, clinical stage, metastasis in laryngeal carcinoma.

PMID- 18720889
TI  - Editorial: farmer suicides in India: the role of psychiatry and anthropology.

PMID- 18720888
TI  - [Construction of recombinant adenoviral vector to coexpress human neurotrophin3
      and EGFP gene and its conduction efficiency to rat cochlea in vitro].
AB  - OBJECTIVE: To construct an adenoviral vector that codes for both human NT3 and
      EGFP, to confirm the transduction efficiency in rat cochlear cultures and to
      assess the protection of NT3 on SGNs survival. METHOD: PAdeasy-1 and pAdTrack CMV
      were used to constructed Ad/NT3 adenovirus and then to transfer postnatal day 3
      rat cochlear cultures. The transduction efficiency was determined by microscope
      observation. The amounts of SGNs were counted to evaluated protection of Ad/NT3
      on SGNs survival. RESULT: EGFP positive cells were observed in all cochlear
      turns. There was approximately 49% in outer sulcus cells and 27% in the
      interdental cells; less than 2% of the hair cells and SGN. The amounts of SGN of
      treated Ad/NT3 adenovirus are more than cochlea SGN only Ad/EGFP adenovirus after
      cultured for 15 days. CONCLUSION: Ad/NT3 adenovirus could transduce EGFP and NT3
      in large number of supporting cells, but few hair cells or SGNs. The putative
      release of NT3 from these supporting cells could enhance cell survival and
      promote neurite outgrowth from SGNs.

PMID- 18720890
TI  - Trained volunteer-delivered mental health support to those bereaved by Asian
      tsunami--an evaluation.
AB  - INTRODUCTION: While mental health consequences following the Asian December 2004
      tsunami have been studied, its impact on the survivors who lost close family
      members deserves attention. We investigated the usefulness of trained volunteer
      delivered mental health support for the bereaved persons. METHOD: Non-randomized
      control design involving all adults aged 18 years or above who lost at least one
      close family member during tsunami from two geographically different coastal
      areas in Chennai, India. From the intervention and control sites, 45 and 57
      participants were recruited respectively for the study. One year after baseline
      assessment, all 102 participants in intervention and control sites were
      interviewed. RESULTS: Participants receiving interventions on a consistent basis
      from trained volunteers were less likely to report depressive symptoms and
      general psychological distress compared with participants who did not receive the
      above intervention. Regression analysis for predicting the effect of intervention
      on the difference between the baseline and follow-up in BDI as well as GHQ
      scores, found a significant association between intervention and the improvement
      in BDI (adjusted beta (SE): -0.53 (2.44); p = 0.000) and GHQ (adjusted beta (SE):
      -0.52 (1.81); p = 0.001) scores. Suicidal attempts were also significantly less
      in the intervention group (FET p = 0.02). CONCLUSION: In settings where mental
      health professionals are limited in number, trained lay volunteers can offer
      empathetic listening, support and referrals that can be potentially beneficial.

PMID- 18720891
TI  - Family caregiving in bipolar disorder: caregiver consequences, caregiver coping
      styles, and caregiver distress.
AB  - AIMS: This study investigated the consequences caregivers of outpatients with
      bipolar disorder are confronted with, the distress they experience and their
      coping styles. METHODS: Caregivers (n = 115) were asked to complete the
      Involvement Evaluation Questionnaire (IEQ) to measure caregivers' consequences,
      the Utrecht Coping List (UCL) to measure caregivers' coping styles, and the 12
      item General Health Questionnaire (GHQ-12) to measure caregiver distress. Scale
      (sub)scores were calculated and relationships between the results were explored.
      RESULTS: Caregiver consequences were found to be limited, although approximately
      30% reported distress. Male caregivers used a more avoiding coping style and
      undertook activities to provide diversion. Female caregivers used a less active
      approach and sought less social support. Correlations were found between the IEQ
      overall score and its subscales 'tension' and 'worrying' and the UCL subscales
      'palliative reaction pattern' and 'passive reaction pattern'. Distress appears to
      occur more often in caregivers who report more consequences, tend to use a more
      avoiding coping style, and have a more passive reaction pattern. CONCLUSIONS:
      Clinicians should assess symptoms of caregiver distress. When caregiver distress
      is noticed, efforts should be undertaken to support the caregiver and teach them
      skills to cope effectively with the consequences they experience in order to stay
      well.

PMID- 18720892
TI  - The value of routine outcome measurement for consumers of mental health services:
      master or servant?
AB  - BACKGROUND: Standardized instruments have been introduced for routine use within
      Victorian mental health services. The aim of routine outcome measurement (ROM) is
      to ensure the highest standard of service delivery as demonstrated through
      quality and accountability processes. AIMS: The aim is to determine the extent to
      which ROM measure against the 12 principles of outcome measurement described by
      Smith et al. (1997). METHOD: The three ROM currently used in Victoria were
      critiqued according to the 12 principles, with the support of a review of the
      literature regarding outcome measurement. RESULTS: Of the 12 principles
      articulated, nine are not met by ROM currently used in Victoria. Only one is
      fully met, one partially met and one cannot be conclusively decided either way in
      light of current knowledge. CONCLUSIONS: ROM currently utilized in Victoria do
      not reflect the areas considered of most relevance and importance to consumers of
      mental health services. Priority should therefore be given to developing an
      alternative consumer-derived approach to determining the effectiveness of mental
      health services according to those most affected by them.

PMID- 18720893
TI  - The healthcare-seeking behaviour of schizophrenic patients in Cambodia.
AB  - AIMS: To understand the patterns of the schizophrenic patients' healthcare
      seeking behaviour (HCSB) in the context of a post-conflict country where
      psychiatric facilities are scarce. METHODS: Cross-sectional survey assessing
      schizophrenic patients and their caregivers who consulted for the first time in
      four different outpatient psychiatric departments. RESULTS: One hundred and four
      schizophrenic patients were selected: 56.7% began the HCSB with traditional
      medicine; 22.1% with western medicine, psychiatry included, and 20.2% with
      religious medicine; 77.3% did not begin the HCSB with psychiatry because they did
      not know it was a mental problem or because they did not know mental health
      services existed. The patients' education was the only factor that significantly
      influenced the HCSB. CONCLUSION: In Cambodia, traditional and religious medicine
      are the first pathway to mental healthcare when patient and caregiver decide to
      seek help due to psychotic symptoms. The lack of knowledge on mental health and
      facilities appears the main reason to explain the schizophrenic patients' HCSB.
      This suggests that the development of psychiatry in Cambodia will be facilitated
      by a better spreading of knowledge on mental health and will have to take
      traditional and religious medicine into account.

PMID- 18720895
TI  - Stalking behaviour by patients towards psychiatrists in a large mental health
      organization.
AB  - BACKGROUND: Mental health professionals are at greater risk than the general
      population of being stalked, particularly by patients. AIMS: To assess the
      prevalence of stalking behaviour by patients towards psychiatrists and ascertain
      patient characteristics. METHOD: Semi-structured questionnaire to all
      psychiatrists (n = 324) working in a large mental health organization. RESULTS:
      The response rate was 61% (n = 198). Forty-one doctors (21%) reported having been
      stalked by patients, the majority being consultants (n = 31; 76%). No sub
      speciality was over-represented. Most stalkers (n = 24; 59%) were male with a
      diagnosis of personality disorder (39%) or major mental illness (34%). Duration
      of stalking ranged from several weeks to 16 years, and most commonly occurred at
      work. On average, victims experienced two types of inappropriate contact.
      Physical threats were made against 14 psychiatrists (34%). CONCLUSIONS: Stalking
      by patients towards psychiatrists is common and represents an important
      occupational risk. Formal training programmes and policy development within
      healthcare organizations may help manage risk.

PMID- 18720894
TI  - Measuring acculturation and symptoms of depression of foreign immigrants in the
      Athens area.
AB  - BACKGROUND: Acculturation is the phenomenon that results when a group with one
      culture comes into continuous contact with a host culture and changes occur in
      the original culture of either one or both groups. Acculturation has also been
      linked with stress-related psychological disorder and depression. AIMS: This
      article investigates the acculturation process and the depressive state of
      foreign immigrants living in the greater Athens area. METHODS: All consecutive
      cases of 157 foreign immigrants who visited a nongovernmental organization (NGO)
      providing consultative services to immigrants were interviewed using a structured
      questionnaire including the Immigrant Acculturation Scale (IAS) and the Centre
      for Epidemiologic Studies - Depression (CES-D) scale. RESULTS: Factor analysis of
      IAS yielded a three-factor solution and 17 items with loadings ranging from 0.74
      to 0.41. This scale was also tested and proven to be reliable. The main finding
      is that the higher the acculturation level of the immigrant individual, the lower
      the CES-D scale score; the fewer the depressive symptoms are self-reported.
      Length of stay, existence of family in Greece, legal status of residence and
      employment were also found to have an effect on depressive symptomatology.
      CONCLUSION: Acculturation could be seen as a beneficial mechanism protecting the
      individual to be exposed to stressful non-adaptive behaviour.

PMID- 18720896
TI  - Whose life am i living? Relatives living in the shadow of depression.
AB  - BACKGROUND: Families living with mental illness experience added burden and need
      information and support. AIM: This aim of this study was to explore the
      experiences of families living close to a depressed individual. METHODS: Eighteen
      persons were interviewed individually or in focus groups. Data was analysed using
      a grounded theory-inspired methodology. RESULTS: Most participants expressed a
      feeling of not living their own life, struggling to balance relationships,
      adapting to and re-evaluating their life circumstances, and struggling to voice
      their ill relatives' and their own needs. CONCLUSIONS: More can be done to help
      and sustain hope in the relatives of persons with depression.

PMID- 18720897
TI  - Online video game therapy for mental health concerns: a review.
AB  - BACKGROUND: There has been research on the use of offline video games for
      therapeutic purposes but online video game therapy is still fairly under
      researched. Online therapeutic interventions have only recently included a gaming
      component. Hence, this review represents a timely first step toward taking
      advantage of these recent technological and cultural innovations, particularly
      for the treatment of special-needs groups such as the young, the elderly and
      people with various conditions such as ADHD, anxiety and autism spectrum
      disorders. MATERIAL: A review integrating research findings on two technological
      advances was conducted: the home computer boom of the 1980s, which triggered a
      flood of research on therapeutic video games for the treatment of various mental
      health conditions; and the rise of the internet in the 1990s, which caused
      computers to be seen as conduits for therapeutic interaction rather than
      replacements for the therapist. DISCUSSION: We discuss how video games and the
      internet can now be combined in therapeutic interventions, as attested by a
      consideration of pioneering studies. CONCLUSION: Future research into online
      video game therapy for mental health concerns might focus on two broad types of
      game: simple society games, which are accessible and enjoyable to players of all
      ages, and online worlds, which offer a unique opportunity for narrative content
      and immersive remote interaction with therapists and fellow patients. Both genres
      might be used for assessment and training purposes, and provide an unlimited
      platform for social interaction. The mental health community can benefit from
      more collaborative efforts between therapists and engineers, making such
      innovations a reality.

PMID- 18720899
TI  - Temporal, seasonal, and regional differences in births and deaths in Aland
      (Finland).
AB  - A good knowledge of the seasonal variation during normal years is of fundamental
      importance for analyses of the effects of wars, famines, epidemics, or similar
      privations on births and deaths. In this study we consider data from the Aland
      Islands (Finland) for 1650-1950. During the period 1650-1793 there are subperiods
      with missing data for all parishes, and consequently the total data for the Aland
      Islands for this period have to be estimated using available data. For the period
      1794-1950 the registered data seem to be complete and reliable, but the war year
      1809 shows a marked deficit of births. During the last decades of the 19th
      century the number of births increases markedly and after that shows a strong
      decrease. After the 1930s births increase again. To allow seasonality comparisons
      between the Aland Islands as a whole and its subregions, we base our studies on
      seasonal indexes. There is a markedly decreasing temporal trend in the seasonal
      variation of births for the Aland Islands as a whole, but the general pattern
      remains mainly the same, having two peaks, one in March-April and one in
      September-October. For the period 1901-1950 the seasonal variation almost
      disappeared. The strength of the seasonal variation in births shows regional
      differences, but the general pattern is mainly the same. The outermost parish,
      Kokar, an isolate of its own, shows the strongest seasonal variation in births.
      The annual number of deaths shows some marked peaks, especially in the war year
      1809. For both sexes there are marked peaks in 1809, indicating that the deaths
      were mainly caused by epidemic diseases rather than by killing in battles. For
      mortality a decreasing trend in the seasonal variation is observed during 1650
      1750, but after 1751-1800 the strength of seasonality shows an increasing trend
      and a sinusoidal pattern.

PMID- 18720898
TI  - Applying novel genome-wide linkage strategies to search for loci influencing type
      2 diabetes and adult height in American Samoa.
AB  - Type 2 diabetes mellitus (T2DM) is a common complex phenotype that by the year
      2010 is predicted to affect 221 million people globally. In the present study we
      performed a genome-wide linkage scan using the allele-sharing statistic Sall
      implemented in Allegro and a novel two-dimensional genome-wide strategy
      implemented in Merloc that searches for pairwise interaction between genetic
      markers located on different chromosomes linked to T2DM. In addition, we used a
      robust score statistic from the newly developed QTL-ALL software to search for
      linkage to variation in adult height. The strategies were applied to a study
      sample consisting of 238 sib-pairs affected with T2DM from American Samoa. We did
      not detect any genome-wide significant susceptibility loci for T2DM. However, our
      two-dimensional linkage investigation detected several loci pairs of interest,
      including 11q22 and 21q21, 9q21 and 11q22, 1p22-p21 and 4p15, and 4p15 and 15q11
      q14, with a two-loci maximum LOD score (MLS) greater than 2.00. Most detected
      individual loci have previously been identified as susceptibility loci for
      diabetes-related traits. Our two-dimensional linkage results may facilitate the
      selection of potential candidate genes and molecular pathways for further
      diabetes studies because these results, besides providing candidate loci, also
      demonstrate that polygenic effects may play an important role in T2DM. Linkage
      was detected (p value of 0.005) for variation in adult height on chromosome 9q31,
      which was reported previously in other populations. Our finding suggests that the
      9q31 region may be a strong quantitative trait locus for adult height, which is
      likely to be of importance across populations.

PMID- 18720900
TI  - Temporal variation in phenetic affinity of early Upper Egyptian male cranial
      series.
AB  - We carried out an exploratory historical biology study using temporally
      distinguished groups of predynastic-Early Dynastic male crania from the region of
      Upper Egypt. The objectives were, first, to determine the overall pattern of
      phenetic affinity between temporally sequential series and in relation to the
      earliest series and, second, to explore the possible meanings of the pattern of
      relationship to sociohistorical change. The cranial series were designated early
      predynastic, late predynastic, terminal predynastic, and Dynasty I. Craniometric
      phenetic affinity was ascertained using Mahalanobis distances; a 5% level of
      probability was chosen for significance. The distance matrix values were ordered
      into hierarchies of dissimilarity from each series (distance hierarchies) and
      tabulated for time-successive groups, including the temporally earliest series
      (i.e., serialized by time). The principal observations were as follows. The
      overall pattern was not one in which the values between all series were
      statistically insignificant; nor was it one of consistent sequential increase of
      biological distance from the earliest series. There was a notable and
      statistically significant distance between the early and late predynastic groups,
      with the late and terminal predynastic groups mutually having the lowest and
      statistically insignificant distances with each other. The value between the
      terminal predynastic and Dynasty I series was generally larger than the values
      between other groups and was statistically significant. The overall pattern is
      possibly consistent with archeological interpretations that postulate increasing
      intraregional interactions during the late and terminal predynastic periods and
      the rise of an Egyptian state that eventually included northern Egypt.

PMID- 18720901
TI  - Genetic profiling of genes from the oxidative stress pathway among North and
      South Indians.
AB  - The case-control association study design has been extensively used for
      elucidating the genetic basis of complex traits. Considerable variation in
      frequencies of various gene polymorphisms has been reported across different
      populations and ethnic groups. Thus before beginning such studies, one must know
      the gene variants that exist in the population. Such information is not available
      for the ethnically distinct Indian population, which, on the basis of the
      languages spoken, can be further subdivided into Indo-Europeans (North Indians)
      and Dravidians (South Indians). In this study we provide information on allele
      and genotype frequencies, pairwise linkage disequilibrium, and predominant
      haplotypes in two populations (North India, n=96; South India, n=96) for several
      of the commonly investigated polymorphisms in the oxidative stress pathway genes.
      Of the 33 polymorphisms in 19 genes tested, significant differences in allele and
      genotype frequencies between the two populations were observed for SOD3 Ala58Thr,
      UCP1-3826 C/T, NOS3-786 T/C, and TNFA-308 G/A polymorphisms.

PMID- 18720902
TI  - Population distribution of the methionine allele at the PRNP codon 129
      polymorphism in Europe and the Middle East.
AB  - Methionine homozygosity at codon 129 of the prion protein gene is a risk factor
      for Creutzfeldt-Jakob disease. Knowledge of M129V polymorphism in normal
      populations may contribute to a better understanding of prion diseases. M129V
      polymorphism was studied in 2201 normal subjects, originating from 15 populations
      from Europe and the Middle East. Mean heterozygosity in these populations is
      38.9%, and there is some significant geographic heterogeneity between them. A
      comparison of M129 allele frequencies in these 15 populations to those already
      published for 8 European countries plus Turkey shows significant correlations
      with both latitude (r = -0.77) and longitude (r = 0.69). The geographic map of
      methionine allele frequencies indicates an east-west gradient of decreasing
      methionine allele values from the Middle East to Western Europe.

PMID- 18720903
TI  - DAT1 VNTR polymorphisms in a European and an African population: identification
      of a new allele.
AB  - Polymorphism frequencies of the dopamine transporter gene (DAT1) hypervariable
      region have been analyzed in a sample of Italian and Ivory Coast individuals. The
      3' untranslated region (UTR) of DAT1 includes a variable number of tandem repeats
      (VNTR) of a 40-bp monomer, ranging from 3 to 13 repeats in Caucasian and African
      populations. In our sample we found alleles with 3 to 16 repeats, and the most
      common alleles were the 10-repeat (DAT1*10) and the 9-repeat (DAT1*9) alleles. We
      also found two rare alleles in the Italian population and four in the Ivory Coast
      population. For the first time the new allele DAT1*16 is described in the
      Ivorians. The Ivory Coast population was not in Hardy-Weinberg equilibrium for
      the DAT1 locus because of a deficit of heterozygote genotypes. The observed
      heterozygosity of the Ivorian population was half that of the Italians. The lower
      observed heterozygosity and deviation from Hardy-Weinberg equilibrium could be
      the result of microevolutionary trends, such as genetic drift and/or inbreeding,
      acting on the relatively small and isolated population sampled for this study,
      although some sort of selective pressures acting against the shorter alleles
      cannot be excluded. This evidence, in association with the reduced polymorphism
      shown by the DAT1 VNTR compared to other VNTRs, seems to indicate that the DAT1
      locus may be under some selective pressure.

PMID- 18720904
TI  - Role reversal.

PMID- 18720906
TI  - What do you wish you had been taught in nursing school, but weren't?

PMID- 18720907
TI  - Zen Yoga: good medicine for surgical patients.

PMID- 18720908
TI  - Pediatric asthma.

PMID- 18720909
TI  - Lysosomal storage diseases.

PMID- 18720910
TI  - A helping paw.

PMID- 18720911
TI  - Anna's story. Interview by Leonore B Weinstein.

PMID- 18720912
TI  - Controlled compression and liposuction treatment for lower extremity lymphedema.
AB  - In 1987 we noticed excess adipose tissue in a patient with arm lymphedema and
      later, objective studies confirmed this clinical finding in patients with non
      pitting arm lymphedema following breast cancer. A prospective study was begun in
      1993, and its long-term results (15 years) shows overall complete reduction of
      the excess volume in patients with non-pitting arm lymphedema and that adipose
      tissue dominates the excess volume. Encouraged by these results we operated on a
      patient with primary and secondary elephantiasis of the leg. The edema was first
      transferred from a pitting to a non-pitting state by controlled compression
      therapy. Then liposuction was performed to remove the remaining excess adipose
      tissue, and complete reduction was finally achieved. The patient wears
      compression garments continuously and during the 11 years of followup, no
      recurrence has occurred. This paper explains our philosophical approach: a
      pitting lymphedema first should be treated conservatively to remove excess fluid,
      then liposuction can be performed to remove remaining excess volume bothersome to
      the patient.

PMID- 18720913
TI  - Different effects of angiogenesis inhibitors IFN-alpha and TIMP-1 on
      lymphangiogenesis.
AB  - This study was designed to examine the effects of angiogenesis inhibitors IFN
      alpha and TIMP-1 on lymphangiogenesis. We cultured lymphatic endothelial (LE)
      cells from pig thoracic ducts and performed morphological observations using
      light microscopy, TEM, and confocal microscopy to confirm their lymphatic origin.
      We tested these cells for growth inhibition by angiogenesis inhibitors IFN-alpha
      and TIMP-1 using both the scraping line and MTT methods. In addition, we analyzed
      apoptosis using the Hoechst and Caspase staining methods. Finally, we tested IFN
      alpha and TIMP-1 using in vivo inhibitory assays. By morphological observations,
      all LE cells in vivo and in vitro were found to be of very similar morphology.
      Both in vitro inhibitory assays of scraping line and MTT showed significant
      differences for the IFN-alpha treatment (p < 0.01) and no significant difference
      for TIMP-1. Hoechst and Caspase apoptosis assays demonstrated that IFN-alpha
      could induce apoptosis of LE cells, and TIMP-1 had little effect. IFN-alpha and
      TIMP-1 inhibitory in vivo assays showed a lack of healing following IFN-alpha
      treatment compared to control and TIMP-1 treatment. In summary, these different
      angiogenesis inhibitors have different effects on lymphangiogenesis. IFN-alpha
      inhibits proliferation and migration of LE cells in a dose-dependent fashion and
      induces apoptosis of LE cells while TIMP-1 has no significant inhibitory effects
      on proliferation, migration, or inducing apoptosis.

PMID- 18720914
TI  - Asymmetries in breast cancer lateralization and both axillary lymph node number
      and metastatic involvement.
AB  - Previous studies have demonstrated right or left lateralization of some paired
      organ cancers and left-sided asymmetry of different lymph nodes. We investigated
      left-right asymmetry lateralization of breast cancer and distribution of
      involved/ non-involved axillary lymph nodes following metastatic invasion in
      patients with breast cancer. One hundred and sixty five women who underwent
      axillary lymphadenectomy during the study period were included. Right or left
      axillary nodal regions were removed and sent for pathologic examination. Lymph
      nodes were palpatorily identified, isolated from fat tissue, counted and
      macroscopically examined. Pathological examination was performed on formalin
      fixed specimens. We found left-sided lateralization for breast cancer in this
      study group. Both total number as well as the number of axillary lymph nodes
      involved by metastatic breast cancer cells were higher on right side in patients
      with breast cancer on the right side. Although the mechanism is not known, and
      further investigation is needed, this phenomenon may be the result of stronger
      cell-mediated immune activity in the left sides of humans.

PMID- 18720915
TI  - Study of edema reduction patterns during the treatment phase of complex
      decongestive physiotherapy for extremity lymphedema.
AB  - Shortening the treatment phase of complex decongestive physiotherapy (CDP) is
      extremely important both for individual patients and medical economics. In 83
      patients with stage II unilateral secondary extremity lymphedema (31 upper
      extremities and 52 lower extremities), the daily changes in the volume of
      affected extremities during the treatment phase of CDP were prospectively
      investigated. For the upper extremity lymphedemas, the biggest change was seen
      between days 1 (100% residual edema rate) and 2 (46.0 +/- 2.7%; mean +/- SD) of
      therapy with a 54.0% reduction (p < 0.0001). Between days 2 and 3 (38.0 +/- 2.6%)
      of therapy, there was an 8.0% reduction (p < 0.05). From days 3 to 6 of therapy,
      slight changes ranging from 0.2 to 3.2%/day were seen. For the lower extremity
      lymphedemas, the biggest change was seen between days 1 (100%) and 2 (44.5 +/-
      2.1%) of therapy with a 55.5% reduction (p < 0.0001). Between days 2 and 3 (33.5
      +/- 2.6%) of therapy, there was an 11.0% reduction (p < 0.001). The daily volume
      changes from days 4 to 6 were slight, ranging from 0.1 to 1.0%/day. During the
      treatment phase of CDP, the largest volume changes were seen soon after the start
      of therapy.

PMID- 18720916
TI  - Localized tissue water changes accompanying one manual lymphatic drainage (MLD)
      therapy session assessed by changes in tissue dielectric constant inpatients with
      lower extremity lymphedema.
AB  - Previous reports described the utility of assessing local tissue water via tissue
      dielectric constant (TDC) measurements. Our goal was to determine the suitability
      of this method to evaluate lymphedema changes. For this purpose, we measured
      changes in TDC produced by one MLD treatment in 27 legs of 18 patients with lower
      extremity lymphedema. TDC values were measured to a depth of 2.5 mm at the
      greatest leg swelling site before and after one MLD treatment. Girth at the
      target site was measured with a calibrated tape measure. TDC values, which range
      from 1 for zero water to 78.5 for all water within the sampled volume, were
      measured four times and the average used to estimate local changes. Results
      showed that in every case the posttreatment TDC was reduced from its pretreatment
      value with percentage reductions (mean SD) of -9.8 +/- 5.64% (p < 0.0001). Girth
      changes were smaller being -1.5 +/- 1.93% (p < 0.01). We conclude that since TDC
      measurements reflect changes to a depth of about 2.5 mm whereas girth
      measurements reflect conditions of the entire cross-section, TDC assessment may
      be more sensitive to localized lymphedema changes. This finding suggests that TDC
      measurements are useful as complementary and perhaps as independent assessment
      methods of edema/lymphedema and treatment-related changes.

PMID- 18720917
TI  - Humanitarian rescue medical action for patient with advanced lower extremity
      lymphedema.
AB  - No clear data exists regarding the initiating process of medial care delivery in
      cases of humanitarian rescue for advanced and debilitating patient conditions. We
      report on the delivery of care from a hospital located in a rural area in
      Southern Taiwan to a desperate patient from a country across the world in Lima,
      Peru. The patient is a 45-year old woman with unilateral severe, progressive
      primary lymphedema of 26 years who was scheduled to undergo a high femoral
      amputation for infections, lymphatic leak, inability to ambulate, and symptomatic
      cardiomegaly. All arrangements for care, including dental restoration, were made
      by our hospital in collaboration with the government of Peru. Upon multi
      departmental consultation, an 8-hour Charles procedure was performed removing 47
      kg of lymphedematous thigh and leg tissue. Eleven months postoperatively the
      patient is healed and ambulating without assistance. Her weight dropped from 120
      to 73 kg. This case of humanitarian action demonstrates intense collaboration and
      coordination between two governments with dialogue, diplomatic success, a
      lymphedema surgical feat, and ultimately a successful outcome for the patient.

PMID- 18720918
TI  - Gestational trophoblastic disease: presentations from the XLVTH World Congress on
      Gestational Trophoblastic Diseases.

PMID- 18720919
TI  - Blood test for placental site trophoblastic tumor and nontrophoblastic malignancy
      for evaluating patients with low positive human chorionic gonadotropin results.
AB  - OBJECTIVE: To examine utility of measurement of proportions of free beta-subunit
      of human chorionic gonadotropin (hCG) in diagnosis of placental site
      trophoblastic tumor (PSTT) and nontrophoblastic neoplasm in patients with
      persistent low hCG levels and patients with history of gestational trophoblastic
      diseases. STUDY DESIGN: The USA hCG Reference Service measured proportions of
      free beta-subunit in 128 cases, 45 with active invasive trophoblastic disease and
      83 questionable cases with persistent low hCG levels, with or without history of
      gestational trophoblastic disease (GTD). RESULTS: High proportions of free beta
      subunit (> 30% of total hCG) were identified in 18 of 128 cases, all suspected of
      having PSTT or nontrophoblastic neoplasm, which was reported to referring
      physicians. Within 2 months of testing, hysterectomy or tumor biopsy led to
      histologic proof of PSTT in 13 of the 18 cases and biopsy led to proof of
      nontrophoblastic neoplasm in 5 of the 18 cases. CONCLUSION: We confirm use of
      proportion of free beta-subunit (> 30%) as a seemingly absolute test for
      identifying PSTT and nontrophoblastic neoplasms. It should be used to identify
      and diagnose these malignancies in women presenting with persistent low hCG
      levels outside of pregnancy and in secondary evaluation of patients with a
      history of GTDs.

PMID- 18720920
TI  - Epithelioid trophoblastic tumor: a review of the literature.
AB  - OBJECTIVE: To identify common characteristics and provide suggestions for future
      reporting and management of epithelioid trophoblastic tumors (ETTs). STUDY
      DESIGN: Definitions and treatment strategies are unclear because of low incidence
      and paucity of reported data. Literature search revealed 52 cases of ETT; 67%
      presented with abnormal vaginal bleeding, 36% had prior evidence of molar
      pregnancy and 35% presented with metastases. Mean age at diagnosis was 38 years.
      Mean pregnancy interval was 76 months. Human chorionic gonadotropin levels were
      12-148,460 IU/L. RESULTS: Histologic and immunohistochemical reporting varied
      markedly between centers, as did treatment regimens. A total of 13% were reported
      as dead from disease, though duration of follow-up was variable (range, 1-39
      months). Differentiation of prognostic factors in ETT is problematic. Most
      reported cases lack long-term follow-up, and disease recurrence in ETT can be
      late and complex. Distinguishing ETT from other diagnoses may lead to
      underreporting, with an adverse prognosis associated with diagnostic delay.
      CONCLUSION: Case reporting should contain detailed information on
      clinicopathologic, histologic and immunohistochemical characteristics and
      treatment. Data centralization in these rare tumors may be beneficial in
      identifying relevant prognostic parameters.

PMID- 18720921
TI  - Utility of p57 protein(KIP2) in molar disease to determine its androgenetic
      origin.
AB  - OBJECTIVE: To determine, qualitatively and semiquantitatively, the expression of
      p57 protein in different trophoblastic cell populations of hydatidiform mole and
      anembryonic pregnancy. STUDY DESIGN: We performed an observational study of the
      histopathologic and immunohistochemical findings of 48 cases of hydatidiform mole
      and 2 anembryonic pregnancies. The histologic samples stained with hematoxylin
      eosin were reviewed blindly by 3 pathologists to establish a diagnosis and
      compare it to the previous one. Afterward, immunohistochemical staining was
      performed using a polyclonal antibody on paraffin-embedded, formalin-fixed tissue
      sections. The nuclear staining was assessed in 5 cell types: villous mesenchyme,
      cytotrophoblast, syncytiotrophoblast, intervillous trophoblast and decidua.
      RESULTS: The degree of agreement between the previous histologic diagnosis and
      the current one was excellent (kappa = 0.702). The sensitivity was 82.6% for
      complete and 84% for partial mole. On immunohistochemical analysis, the degree of
      agreement was low (kappa = 0.2). The sensitivity was 53.9% for complete mole and
      59.1% for partial mole. The cell population with the least expression for p57 was
      the cytotrophoblast. The results for anembryonic pregnancies remained the same.
      CONCLUSION: Immunohistochemistry with p57 is a useful method to differentiate
      complete from partial mole, which is important to establish the prognosis of the
      patient.

PMID- 18720922
TI  - Subsequent pregnancy outcomes in patients with molar pregnancy and persistent
      gestational trophoblastic neoplasia.
AB  - OBJECTIVE: To evaluate the subsequent reproductive outcomes in patients with
      complete and partial molar pregnancy and gestational trophoblastic neoplasia
      (GTN) at the New England trophoblastic Disease Center between June 1, 1965, and
      December 31, 2007. STUDY DESIGN: Questionnaires regarding subsequent pregnancies
      were mailed to all patients with current mailing addresses at the New England
      Trophoblastic Disease Center. RESULTS: The subsequent reproductive outcomes in
      patients with complete and partial molar pregnancies and persistent GTN were in
      general the same as those in the general population. However, after an episode of
      molar pregnancy the incidence of molar pregnancy in a later gestation was
      approximately 1%. Additionally, after successful chemotherapy for GTN, the
      incidence of stillbirth was 1.4% in later pregnancies. CONCLUSION: Patients with
      molar pregnancies and GTN should be reassured that they can in general expect a
      normal future reproductive outcome.

PMID- 18720923
TI  - Vaginal metastases in gestational trophoblastic neoplasia.
AB  - OBJECTIVE: To evaluate the clinical experience and outcomes of patients with
      gestational trophoblastic neoplasia (GTN) complicated by vaginal metastases.
      STUDY DESIGN: A review of patients with vaginal metastases from GTN treated at a
      regional trophoblastic disease center from 1962 to 2006. RESULTS: Vaginal
      metastases were present in 36 (4.5%) of the 804 patients treated for GTN. FIGO
      stage was II in 13 patients (36%), III in 22 patients (61%) and IV in 1 patient
      (3%). Twenty-three patients (65%) were low-risk by modified WHO criteria. The
      vaginal metastases were most frequently single lesions (61%) on the anterior
      vaginal wall (49%) with a histologic classification of choriocarcinoma (67%).
      Significant bleeding necessitated blood transfusion (median, 7 units; range, 1-26
      units) in 13 patients (36%). Seven patients (19%) required 1 or more procedures
      for control of bleeding, including excision, suturing and/or hypogastric artery
      ligation/embolization. Twenty-three patients (64%) received single-agent
      chemotherapy with methotrexate and/or actinomycin-D, while 13 patients (36%)
      received multiagent chemotherapy regimens. CONCLUSION: Overall, 29 (81%) of 36
      patients with vaginal metastases were cured. Vaginal metastasis from GTN does not
      uniformly confer a worse prognosis or necessitate multiagent chemotherapy,
      although procedures for control of bleeding may be required.

PMID- 18720924
TI  - The changing role of thoracotomy in gestational trophoblastic neoplasia at the
      New England Trophoblastic Disease Center.
AB  - OBJECTIVE: To review our experience with thoracotomy in gestational trophoblastic
      neoplasia (GTN). STUDY DESIGN: Nineteen thoracotomy patients from our database
      were identified. Thoracotomy was performed for therapeutic reasons in 11 patients
      and to clarify the diagnosis in eight. RESULTS: Among the 11 patients with
      chemotherapy-resistant pulmonary tumors, 10 of 11 (90.9%) achieved remission with
      thoracotomy. Thoracotomy was more likely to be done to clarify diagnosis before
      1980 (83%) than after 1980 (23%) (p = 0.04), when it became more likely to be
      done for therapeutic indications. Ten patients had solitary lung lesions and 9
      had multiple lesions. Four patients died (21%), with an average survival after
      thoracotomy of 149 days; patients had bilateral or multiple lung lesions, median
      preoperative hCG was 58,000 mIU/mL and all were stage IV. Survivors had lower
      stage disease, were more likely to have solitary lesions and had lower
      preoperative hCG levels. CONCLUSION: There have been several temporal changes in
      the indications for thoracotomy for GTN. In general, the optimal patient to
      achieve remission with thoracotomy will have stage III disease, a preoperative
      hCG of < 1,500 mIU/mL, and a solitary lung nodule resistant to chemotherapy.
      Likelihood of remission after thoracotomy is high in properly selected patients.

PMID- 18720925
TI  - Hyperglycosylated human chorionic gonadotropin and human chorionic gonadotropin
      free beta-subunit: tumor markers and tumor promoters.
AB  - Human chorionic gonadotropin (hCG) is a heterogeneous glycoprotein hormone
      comprising an alpha-subunit and beta-subunit that can vary in peptide and
      carbohydrate structure. After conception, hCG produced by early trophoblast cells
      acts on luteinizing hormone (LH)/hCG receptor corpus luteum cells to promote
      progesterone production and establish maternal recognition of pregnancy. hCG is
      not simply 1 molecule, and 2 variants of hCG appear to have independent
      activities in promoting tumor cell growth, invasion and malignancy.
      Hyperglycosylated hCG (H-hCG), produced by cytotrophoblast cells, is a marker for
      cytotrophoblast cells and tumor marker for gestational trophoblastic diseases. H
      hCG promotes growth and invasion in these cells during pregnancy implantation,
      and growth in varying degrees by many nontrophoblastic neoplasms. beta-hCG is a
      marker of poor prognosis shown to promote growth and invasion in vitro,
      suggesting autocrine growth factor properties. Vaccines to beta-hCG have been
      successfully demonstrated, suggesting a potential adjuvant therapy in cancer
      treatment. Although sufficiently distinct in both structure and occurrence,
      similarities have been observed between H-hCG and beta-hCG as promoters of cell
      growth, invasion and malignancy. It is somewhat irregular for 2 structural
      variants of a molecule to have independent actions, actions very different to the
      gonadotropic function of the established hormone hCG.

PMID- 18720926
TI  - The role of adjuvant surgery in the management of gestational trophoblastic
      neoplasia.
AB  - OBJECTIVE: To evaluate the role of different surgical procedures combined with
      chemotherapy in the management of gestational trophoblastic neoplasia (GTN).
      STUDY DESIGN: A retrospective descriptive analysis of data was done using charts
      of diagnosed cases of GTN from 1996 to 2006. The patients were classified
      according to FIGO staging and WHO prognostic scoring. Surgical procedures were
      evaluated as to indications, hospital stay, remission rate and number of
      chemotherapy cycles needed to achieve remission. RESULTS: One hundred thirty-four
      patients underwent at least 1 major surgery in the form of hysterectomy, with
      uterine perforation and profuse vaginal bleeding as an indication for surgery.
      Common indications for adjuvant surgery are completed family size and resistance
      to chemotherapy. Two patients had excision of liver metastases, and 3 patients
      had lung resection. CONCLUSION: With the increasing use of early surgical
      intervention combined with chemotherapy, we feel that we are maximizing the
      benefit that can be derived by our patients from our treatment protocol. We are
      decreasing the number of chemotherapeutic cycles needed to attain remission and
      in effect decreasing the exposure of the patients to toxicity from the
      chemotherapy.

PMID- 18720927
TI  - Role of hysterectomy in managing persistent gestational trophoblastic disease.
AB  - OBJECTIVE: To evaluate incidence, indications and outcomes of hysterectomy for
      gestational trophoblastic disease (GTD) and compare outcomes for patients who
      underwent primary hysterectomy with outcomes for those who underwent adjuvant
      hysterectomy. STUDY DESIGN: Using the Sheffield Trophoblastic Tumour Centre
      database (January 1, 1986, until June 30, 2007), patients who underwent
      hysterectomy were identified, along with age, antecedent pregnancy, diagnosis
      date, hysterectomy date and chemotherapy and pathologic findings. RESULTS: A
      total of 8,860 patients were registered at Weston Park Hospital, Sheffield. Of
      them, 627 (7.1%) needed chemotherapy and 62 (0.71%) underwent hysterectomy. The
      most frequent indication was resistance to chemotherapy in 22 of 62 (35.5%),
      followed by major hemorrhage in 21 of 62 (33.9%). Emergent hysterectomy was
      performed in 22 (35.5%). Mean International Federation of Gynecology and
      Obstetrics risk score was 6.5. Choriocarcinoma was the most frequent pathology
      (23), followed by invasive mole (10) and placental site trophoblastic tumor (9).
      Thirty-one patients needed chemotherapy after hysterectomy, 93.5% are in
      remission, 7 relapsed, 3 were cured and 4 died of disease. CONCLUSION: Incidence
      of hysterectomy for GTD was 1 in 140. Patients who underwent hysterectomy
      represent a high-risk group, often having more aggressive pathology. Hysterectomy
      is valuable as primary and adjuvant treatments.

PMID- 18720928
TI  - Low-risk gestational trophoblastic neoplasia: evaluating the need for initial
      inpatient treatment during low-dose methotrexate chemotherapy.
AB  - OBJECTIVE: To evaluate the need for initial inpatient treatment for patients
      being treated with low-dose intramuscular methotrexate for low-risk gestational
      trophoblastic neoplasia (GTN). STUDY DESIGN: Clinical notes of all patients
      treated with low-dose intramuscular methotrexate for low-risk GTN were analyzed
      and side effects noted. RESULTS: There were no episodes of increased uterine
      bleeding requiring extra medical intervention. There were 7 cases of chest pain;
      none required a change from methotrexate chemotherapy. CONCLUSION: Patients being
      treated with low-dose intramuscular methotrexate for low-risk GTN do not need to
      be treated routinely in the hospital for their first treatment cycle.

PMID- 18720929
TI  - Antigen-specific T cell immune response detected by skewed T cell receptor usage
      in normal placenta and complete molar pregnancy.
AB  - OBJECTIVE: To investigate the antigenicity of normal placenta and complete molar
      trophoblastic tissue. STUDY DESIGN: T cell receptor (TCR) variable beta chain
      (VBC) gene expression was analyzed utilizing fresh frozen tissues. Real-time
      polymerase chain reactions (RT-PCR) were performed on cDNA samples from 10 normal
      buffy coats (BC), 7 normal placentas (NP) and 14 complete molar pregnancies (CM)
      using a TCR beta chain and 25 variable TCR beta chain primers. Relative
      expressions were calculated for each individual gene. RESULTS: Significant
      changes were noted in most of the gene expressions in NP and CM as compared to
      the buffy coat samples. The relative expression of most genes was significantly
      decreased in NP and CM, but VBC gene number 4 was increased in both NP and CM;
      however, a significant difference was noted only between BC and CM (p = 0.023).
      Comparing NP to CM, 5 other VBC gene expressions were decreased significantly in
      the CM tissues (p < 0.05). CONCLUSION: In normal placenta and CM pregnancies, T
      cells appear to express certain TCR VBC genes in a different manner than in BC.
      These genes and the VBC gene profile difference found between NP and CM may play
      an important role in the immunobiology of CM pregnancy.

PMID- 18720930
TI  - Results of treatment of patients with gestational trophoblastic neoplasia
      referred to the Brewer Trophoblastic Disease Center after failure of treatment
      elsewhere (1979-2006).
AB  - OBJECTIVE: To review treatment results of patients with gestational trophoblastic
      neoplasia (GTN) whose care was transferred to the Brewer Trophoblastic Disease
      Center after failure of treatment elsewhere from 1979-2006. STUDY DESIGN: Twenty
      seven (6.6%) of 408 patients with GTN treated at the Brewer Center from 1979-2006
      had received unsuccessful treatment at other institutions prior to transfer to
      our center. Outcomes were analyzed and compared with 37 patients who received
      secondary therapy at the Brewer Center from 1962-1978. RESULTS: Overall survival
      was 93% (25 of 27) in patients treated at the Brewer Center (1979-2006) after
      failed treatment elsewhere. The most common causes of treatment failure prompting
      referral to the Brewer Center were (1) use of a single-agent chemotherapy
      protocol to treat high-risk disease in 11 patients (41%), (2) inappropriate use
      of weekly methotrexate chemotherapy in 9 patients (33%), (3) failed sequential
      single-agent chemotherapy in 4 patients (15%), (4) use of the wrong multiagent
      chemotherapy for high-risk disease in 1 patient (4%) and (5) relapse from
      remission in 2 patients CONCLUSION: Successful secondary treatment of GTN
      improved from 59% during 1962-1978 to 93% during 1979-2006 as a result of better
      chemotherapy protocols and experience treating the disease.

PMID- 18720931
TI  - Diagnosis and treatment of high-risk metastatic gestational trophoblastic
      neoplasia in Hungary.
AB  - OBJECTIVE: To review results in treatment of high-risk metastatic gestational
      trophoblastic neoplasia (GTN) in Hungary. STUDY DESIGN: Between January 1, 1977,
      and December 31, 2006, 142 patients with high-risk metastatic GTN were treated.
      Patients were 14-51 years of age (average 27.9). We selected primary chemotherapy
      based on patient GTN stage and prognostic score. RESULTS: Methotrexate,
      actinomycin-D and cyclophosphamide (MAC) as a primary therapy was used in 100
      cases and as second-line chemotherapy in 6 cases. Of the 100 cases, 95 achieved
      complete remission. Twenty-one high-risk patients were treated with etoposide,
      high-dose methotrexate with folinic acid rescue, actinomycin-D, cyclophosphamide
      and vincristine (EMA-CO). Of 17 primary therapies, 13 patients achieved complete
      remission. Primary cisplatin, etoposide and bleomycin (CEB) was successful in 12
      of 14 high-risk cases. Hysterectomy was performed in 42 of 142 high-risk
      patients; metastases were resected in 26 of 142 of high-risk patients. Comparison
      of mean prognostic scores resulted in significant differences between CEB and
      MAC, CEB and EMA-CO and MAC and EMA-CO. CONCLUSION: Results support that patients
      with high-risk metastatic GTN should primarily be treated with combination
      chemotherapy. Our data support the effectiveness of MAC, EMA-CO and CEB regimens.

PMID- 18720932
TI  - EGFR-immunohistochemistry in colorectal cancer and non-small cell lung cancer:
      comparison of 3 commercially available EGFR-antibodies.
AB  - BACKGROUND: Epidermal Growth Factor Receptor (EGFR)-targeted therapies are
      currently used for the treatment of metastasized colorectal cancer (CRC) and non
      small cell lung cancer (NSCLC). Patient selection for this treatment is based on
      immunohistochemical (IHC) testing for EGFR. The rising amount of commercially
      available EGFR-antibodies makes standardisation of EGFR-IHC necessary. The goal
      of this study was to analyse possible discrepancies between 3 antibodies against
      EGFR. PATIENTS AND METHODS: 36 formalin-fixed samples of CRC (n = 26) and NSCLC
      (n = 10) were stained with 3 antibody-clones: 2-18C9 (Dako); 31G7 (VentanaTM) and
      111.6 (Labvision Neomarkers). Interpretation of stains includes assessment of %
      positive cells, evaluation of cut off values and staining intensity. RESULTS:
      With a 1% cut-off, the 2-18C9 clone stained 86% of the cases positive, the 31G7
      clone 77% and the 111.6-clone 52%. With a 10% cut-off, percentages declined to
      77%, 61% and 30% respectively. The 2-18C9-clone showed the highest staining
      intensity. The 2-18C9 clone and the 31G7-clone showed a concordance rate of 90%.
      CONCLUSIONS: IHC staining with 3 different antibody clones directed against EGFR
      shows indeed differences in staining results: the percentage of positive cells
      and staining intensity are variable. A correct cut-off value for a positive
      result is important and can be different depending upon the antibody. Appropriate
      validation of an antibody is essential before it can be used for selection of
      patients.

PMID- 18720933
TI  - EUS-FNA and FDG-PET are complementary procedures in the diagnosis of enlarged
      mediastinal lymph nodes.
AB  - BACKGROUND AND STUDY AIMS: Transoesophageal endosonography with fine needle
      aspiration (EUS-FNA) and 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron
      emission tomography (FDG-PET) are now standard diagnostic procedures of the
      mediastinum. Our aim was to compare their value in the assessment of enlarged
      mediastinal lymph nodes detected by computed tomography. PATIENTS AND METHODS:
      Forty consecutive patients with a suspicion of cancer or a history of pulmonary,
      digestive, urogenital or mammary neoplasia and presenting with supracentimetric
      lymph nodes on computed tomography underwent whole body FDG-PET and EUS-FNA.
      Final diagnosis of malignancy was obtained by cytology, surgery or long-term
      follow-up. RESULTS: EUS-FNA showed a sensitivity, specificity and accuracy for
      detection of malignancy of 793, 100 and 85%, respectively. The biopsy material
      was adequate for cytological examination in 37 patients. Sensitivity, specificity
      and accuracy of PET were 100, 54.5 and 87.5%, respectively. FDG-PET correctly
      diagnosed the primary site in 27 patients, and showed additional unknown
      extrathoracic metastatic sites in 15 patients. The five false positive results
      observed with FDG-PET consisted in a final diagnosis of sarcoidosis,
      tuberculosis, anthracosilicosis and reactive lymph nodes, respectively. The
      association of FDG-PET and EUS-FNA avoided more invasive procedures
      (mediastinoscopies or staging surgery) in 34 patients. CONCLUSIONS: EUS-FNA and
      FDG-PET are complementary diagnostic procedures combining the high sensitivity of
      FDG-PET and the high specificity of EUS-FNA to accurately diagnose malignancy in
      enlarged mediastinal lymph nodes identified by CTscan. The combination of the two
      procedures in selected cases with pulmonary cancer or extra-thoracic tumours
      avoided more invasive diagnostic and surgical procedures.

PMID- 18720934
TI  - An economic evaluation of vasoactive agents used to treat acute bleeding
      oesophageal varices in Belgium.
AB  - BACKGROUND AND STUDY AIMS: Increasingly, cost influences all areas of healthcare,
      including the management of life threatening events, such as bleeding oesophageal
      varices (BOV). In light of the need to control costs, an economic evaluation of
      vasoactive agents used to treat cirrhotic patients with BOV within the emergency
      setting in Belgium has been assessed. PATIENTS AND METHODS: A previously reported
      economic evaluation of vasoactive agents used to treat BOV was identified and
      adapted to the Belgium hospital setting. The economic evaluation was based on
      double-blind randomised controlled trials of vasoactive agents previously
      reported as Cochrane meta-analyses. Belgian cost data was obtained from local
      published sources and hospital databases. We assessed average disaggregated and
      aggregated treatment costs, average and incremental cost per quality adjusted
      life years (QALYs) and life-years gained (LYG). RESULTS: Total treatment costs at
      1 year were: terlipressin Euro 2,734; somatostatine Euro 2,972; octreotide Euro
      2,801; and placebo Euro 2,874. The average costs per QALY were: terlipressin Euro
      4,672; somatostatine Euro 5,878; octreotide Euro 5,540; and placebo Euro 5,687.
      In the cost per LYG analysis terlipressin achieved the lowest cost per life-year.
      Results from the incremental cost per QALY and LYG analysis indicated that
      terlipressin was the most cost-effective agent. CONCLUSIONS: One year simulations
      indicate somatostatine is the most expensive treatment option and terlipressin
      the least costly. Amongst the vasoactive products, the incremental analysis
      indicated terlipressin was dominant when compared with octreotide and
      somatostatine because of improved survival and cost-saving potential that is
      likely attributed to avoiding additional and more costly interventions.

PMID- 18720935
TI  - Porphyria cutanea tarda and liver disease. A retrospective analysis of 17 cases
      from a single centre and review of the literature.
AB  - BACKGROUND/AIMS: Sporadic Porphyria Cutanea Tarda (sPCT) is associated with liver
      disease, e.g. HCV infection, haemochromatosis and especially alcoholic liver
      disease. We conducted a retrospective analysis on the prevalence of liver
      disorders in association with Porphyria Cutanea Tarda (PCT), in a university
      referral centre. METHODS: The PCT cases were retrieved from computerized
      databases. Patient files lacking information on the presence of concomitant liver
      disease were excluded from further analysis. RESULTS: 29 PCT patients were
      retrieved from our databases, of which 17 patients with sPCT were retained for
      further analysis. Patients were middle aged (mean age: 43 +/- 3) and there was no
      gender difference (10 males vs. 7 females). Almost all patients had iron overload
      (14/17). 5 patients had chronic HCV, with type 1b in 3 of them, 7 abused alcohol,
      4 patients had hereditary haemochromatosis (3 homozygous C282Y--1 heterozygous
      H63D/C282Y). In 3 patients sPCT was associated with medication intake and one
      patient had chronic hepatitis B (HBV). 13 patients were treated with
      phlebotomies, with success in 11/13. 4 patients were treated with chloroquine, 3
      of which also underwent phlebotomies. Of the 5 patients with HCV, 3 were
      successfully treated with combined antiviral therapy; one of them is planned to
      be treated; one patient never received therapy and was lost from follow-up. One
      patient developed hepatocellular carcinoma (HCC) during a median follow-up of 24
      years. CONCLUSIONS: We found a significant association between sPCT and liver
      disorders, such as chronic HCV infection, alcohol abuse, iron overload and
      hereditary haemochromatosis. Therefore, patients presenting with PCT should be
      screened for concomitant liver disease. Iron overload is present in a majority of
      patients, the majority of patients can be successfully treated with phlebotomies.
      The risk of developing HCC in our sPCT patients and in literature is low.

PMID- 18720936
TI  - One-step chromoendoscopy and structure enhancement using balsamic vinegar for
      screening of Barrett's esophagus.
AB  - BACKGROUND AND STUDY AIMS: Screening for specialized columnar epithelium (SCE)
      within columnar lined esophagus (CLE) with standard video endoscopes is not
      reliable enough. Several methods to improve accuracy of predicting presence of
      SCE like chromoendoscopy with vital stains or structure enhancement with acetic
      acid have been introduced but data up to now remains controversial. The present
      prospective study was conducted to evaluate a combination of chromoendoscopy and
      acetic acid structure enhancement using the naturally brownish coloured balsamic
      vinegar during routine upper endoscopy. PATIENTS AND METHODS: Between March and
      July 2006 20 patients with macroscopic suspicion for SCE during routine endoscopy
      were included prospectively. Saline diluted balsamic vinegar (3%) was
      administered with a spraying catheter at the distal esophagus. After 1 minute the
      distal esophagus was evaluated for the presence of SCE according to the mucosal
      surface pattern (pattern I-II: round pits/circular pattern predicting gastric
      epithelium; pattern III-IV: ridged/villous pattern predicting Barrett's
      epithelium). Only HR-videoendoscopes without magnification were used. After
      presence or absence of SCE was defined by the endoscopist targeted biopsies of
      the CLE were performed. Histological results were compared with endoscopic
      findings. RESULTS: In 9 of 20 patients (13 male, 7 female; mean age 60.0 +/- 12.8
      years) biopsy specimen revealed SCE within CLE on histology. Prediction of BM
      after balsamic vinegar staining was possible in all cases. Surface pattern I-II
      was found in 9 patients and pattern III-IV in 11 patients. Accuracy, sensitivity
      and specificity for BV staining predicting SCE were 90%, 100% and 82%,
      respectively. CONCLUSION: Chromoendoscopy with balsamic vinegar combines the
      advantages of chromoendoscopy and structure enhancement by acetic acid for
      detection of SCE. The reliability in predicting the presence of SCE was high in
      this prospective feasibility study.

PMID- 18720937
TI  - Addition of somatostatin-14 to a standard total parenteral nutrition-mixture in
      the treatment of fistulae: a clinical, double-blind, randomised, cross-over
      study.
AB  - BACKGROUND/STUDY AIMS: Somatostatin and total parenteral nutrition (TPN) are
      routinely used in the treatment of pancreatic and enterocutaneous fistulae. The
      objective of this clinical randomised cross-over study was to investigate the
      serum levels of somatostatin infused alongside TPN by a separate intravenous
      line, and when it had been added to the TPN mixture. PATIENTS/METHODS: The
      subjects were recruited by the treating physicians and the nutrition nurses. From
      the patients who started the study, no one dropped out. Ten patients were treated
      with a standard TPN mixture and somatostatin 6 mg/day. Patients were randomised
      to two possible regimens: 'somatostatin plus TPN--somatostatin separately-
      somatostatin plus TPN' or 'somatostatin separately--somatostatin plus TPN-
      somatostatin separately'. Each regimen consisted of 3 x 3 days of therapy, during
      which, serum levels of somatostatin were measured daily. Pre- and posttreatment
      samples were also analysed. RESULTS: When somatostatin was infused separately,
      the mean serum level was 884.8 pg/ml (SD: 557.3; range: 54-1900). When added to
      TPN, the mean serum level was 807.5 pg/ml (SD: 505.8; range 162-2279) (p value of
      difference = 0,473). The mean pretreatment level was 17.1 pg/ml (SD: 7.5; range:
      8-33), and posttreatment was 32.8 pg/ml (SD: 26.5; range: 16-97). CONCLUSIONS:
      These results demonstrate that serum levels of somatostatin are similar in both
      treatment regimens and therefore may be added to a TPN mixture.

PMID- 18720938
TI  - Primary aorto enteric fistula: report of 18 Belgian cases and literature review.
AB  - BACKGROUND AND STUDY AIMS: We searched for Belgian cases of primary aorto enteric
      fistula (PAEF). After reviewing the literature we compared our data concerning
      incidence, types, pathogenesis, aetiology, clinical presentation, diagnostic
      modalities, treatment and prognosis of PAEF. We especially focus on the clinical
      picture and diagnostic options. PATIENTS AND METHODS: We present our atypical
      case report. A questionnaire was send to 196 Belgian vascular surgeons in order
      to evaluate retrospectively the Belgian experience with PAEF. A Medline search of
      relevant literature from January 1980 to February 2006 was conducted. RESULTS: In
      total 18 Belgian cases of PAEF were detected usually originating from infrarenal
      abdominal aorta (83%), ending in the third or fourth part of the duodenum (67%)
      and affecting men (94%) with a mean age of 70-years-old. Main cause is aneurysm
      (89%). Gastrointestinal bleeding is the main symptom (83%). Untreated, no one
      survives and overall mortality is 29%. Most patients are treated with in situ
      grafts (83%). With our experience we propose a diagnostic flow chart to obtain
      early diagnosis of PAEF. CONCLUSIONS: PAEF is suspected when a patient presents
      with (considerable) (upper) gastrointestinal blood loss and has a known aneurysm,
      initial herald bleed or pulsating abdominal mass. In case of hemodynamic
      instability, prompt surgical exploration is mandatory. Hemodynamically stable
      patients must undergo contrast enhanced multislice computerized tomography rather
      than gastroduodenoscopy or arteriography to make early diagnosis. Surgery is the
      only definitive life saving treatment. Overall mortality is at least 30%. Late
      diagnosis, positive peroperative cultures and shock are indicators of poor
      prognosis.

PMID- 18720939
TI  - Peripheral parenteral nutrition in protracted hyperemesis gravidarum--report of
      two cases and a literature review.
AB  - Hyperemesis gravidarum is defined as severe nausea and vomiting during the first
      trimester of pregnancy. It is characterized by dehydration, electrolyte
      imbalance, ketonuria and weight loss of more than 5% of body weight and it
      usually requires hospitalization. Traditionally, total parenteral nutrition has
      been used when patients with hyperemesis gravidarum fail to respond to
      conservative measures, including dietary manipulation and antiemetics. Total
      parenteral nutrition has been shown to be an effective method of nutritional
      support during pregnancy but it is expensive and has potentially serious
      complications. Peripheral parenteral nutrition reduces the risk of complications,
      but caloric intake is limited. A small number of investigators have suggested
      using enteral nutrition as an alternative to total parenteral nutrition. Herein
      we report two cases of hyperemesis gravidarum successfully treated with an
      effective regimen of peripheral parenteral nutrition.

PMID- 18720940
TI  - Jejunal ischaemia-- rare aetiologies and a surgical dilemma.
AB  - Superior Mesenteric Artery thrombosis can lead to acute mesenteric ischaemia with
      devastating consequences. The main dilemma for the surgeon is the delay in
      diagnosis and a definitive treatment, as these patients may present with signs of
      peritonism but not frank peritonitis until the ischaemia results in infarction
      and or perforation. We report a detailed literature search and a unique case of
      jejunal ischaemia in the setting of undiagnosed Antiphospholipid Syndrome and
      Factor V Leiden heterozygosity where a delayed diagnosis resulted in an
      unnecessary prolongation of patient's morbidity.

PMID- 18720941
TI  - A unique combination of celiac disease, mesenteric lymph node cavitation, splenic
      atrophy and necrotizing hepatitis.
AB  - We report on a patient who was diagnosed six years before with celiac disease,
      with a current combined problem of asplenism, mesenteric cysts and elevated liver
      function tests. The implications of splenic atrophy mimic those of post
      splenectomy patients. Mesenteric lymph node cavitation is a rare complication of
      celiac disease that is most often associated with splenic atrophy. The
      pathogenesis is unknown. The clinical implications of the cavitated mesenteric
      lymph nodes are unclear. The association of celiac disease with liver disease was
      reported many years ago, but only recently these associations have been more
      clearly defined. Liver involvement shows a clinical spectrum varying from
      nonspecific reactive hepatitis, chronic active hepatitis, steatohepatitis to
      frank cirrhosis. Associations with autoimmune hepatitis, autoimmune cholangitis,
      primary biliary cirrhosis and primary sclerosing cholangitis have been described.
      In our patient, we found no obvious cause for the necrotizing hepatitis and the
      negative auto-antibodies made it impossible to firmly establish the diagnosis of
      autoimmune hepatitis. The causal relationship with celiac disease, if any,
      remains unproven.

PMID- 18720943
TI  - Liver teratoma.
AB  - True liver teratomas are exceptional tumors, with only 25 cases reported in the
      radiology literature. Most cases reported were either intraperitoneal or
      retroperitoneal teratomas that had invaded the liver. The authors present a 27
      year-old woman with a liver complex mass found incidentally at computed
      tomography (CT). The different imaging studies demonstrated that the lesion was
      composed of macroscopic fat, with a central soft tissue component and a
      calcification. The patient underwent surgery and the final diagnosis was a benign
      liver teratoma.

PMID- 18720944
TI  - Behcet's disease and celiac disease: is there a controversial link?

PMID- 18720942
TI  - Asymptomatic disseminated carcinomatosis of bone marrow presenting as
      hyperphosphatasia: report of a case.
AB  - Metastatic involvement of the musculoskeletal system is one of the most
      significant clinical issues facing orthopaedic oncologists. The number of
      patients with metastasis to the skeletal system from a carcinoma is 15 times
      greater than the number of patients with primary bone tumours of all types.
      However, progression patterns like disseminated carcinomatosis of bone marrow are
      comparatively rare. The pathophysiology for disseminated carcinomatosis of bone
      marrow, with a prognosis reported to be very poor, is still unknown. We describe
      a patient who had no symptoms with hyperphosphatasia. Bone scintigraphy showed a
      so-called super bone scan and a needle biopsy from the ileum showed
      adenocarcinoma cells. Additional endoscopic investigation was performed and
      signet cell gastric cancer was found. From the bone scan and biopsy, we
      established the diagnosis of disseminated carcinomatosis of the bone marrow. From
      the experience of this case, we believe that intensive stomach investigation
      should be considered in cases with hyperphosphatasia, even when the patient has
      no symptoms.

PMID- 18720945
TI  - Acute hepatitis induced by greater celandine (Chelidonium majus).

PMID- 18720946
TI  - Port-site metastasis after laparoscopic cholecystectomy.

PMID- 18720947
TI  - Profiling of acarviostatin family secondary metabolites secreted by Streptomyces
      coelicoflavus ZG0656 using ultraperformance liquid chromatography coupled with
      electrospray ionization mass spectrometry.
AB  - Profiling of acarviostatin family secondary metabolites secreted by Streptomyces
      coelicoflavus ZG0656 was performed by means of a rapid and facile procedure using
      ultraperformance liquid chromatography coupled with electrospray ionization mass
      spectrometry (UPLC/ESI-MS). The acarviostatins were separated on a C18 UPLC
      column with a series of acetonitrile-aqueous ammonia gradients. The target
      homologues were detected using the multiple reaction monitoring mode, and the
      chemical structures were confirmed by analyzing the diagnostic fragment ions in
      their MS/MS spectra. All six known reference acarviostatins (I03, II03, II13,
      II23, III03, IV03) were thus identified. In addition, at least 74 acarviostatin
      homologues, including 65 novel compounds, were characterized. Some of the
      features of the novel structures included having up to five acarviosine moieties,
      an acarviosine moiety at the reducing terminus, or an incomplete acarviosine
      moiety at the nonreducing terminus. This type of investigation may be useful for
      researchers who study secondary metabolomics in microorganisms and plants,
      especially those who perform metabolic profiling of aminooligosaccharides and
      other natural products with similar structures.

PMID- 18720948
TI  - Multiple stirred-flow chamber assembly for simultaneous automatic fractionation
      of trace elements in fly ash samples using a multisyringe-based flow system.
AB  - There is a current trend in automation of leaching tests for trace elements in
      solid matrixes by use of flow injection based column approaches. However, as a
      result of the downscaled dimensions of the analytical manifold and execution of a
      single extraction at a time, miniaturized flow-through column approaches have
      merely found applications for periodic investigations of trace element mobility
      in highly homogeneous environmental solids. A novel flow-based configuration
      capitalized on stirred-flow cell extraction is proposed in this work for
      simultaneous fractionation of trace elements in three solid wastes with no
      limitation of sample amount up to 1.0 g. A two-step sequential extraction scheme
      involving water and acetic acid (or acetic acid/acetate buffer) is utilized for
      accurate assessment of readily mobilizable fractions of trace elements in fly ash
      samples. The fully automated extraction system features high tolerance to flow
      rates (< or = 6 mL min(-1)) and, as opposed to operationally defined batchwise
      methods, the solid to liquid ratio is not a critical parameter for determination
      of overall readily leachable trace elements provided that exhaustive extraction
      is ensured. Analytical performance of the dynamic extractor is evaluated for
      fractionation analysis of a real coal fly ash and BCR-176R fly ash certified
      reference material. No significant differences were found at the 0.05
      significance level between summation of leached concentrations in each fraction
      plus residue and concentration values of BCR-176R, thus revealing the accuracy of
      the automated method. Overall extractable pools of trace metals in three samples
      are separated in less than 115 min, even for highly contaminated ashes, versus 18
      24 h per fraction in equilibrium leaching tests. The multiple stirred-flow cell
      assembly is thus suitable for routine risk assessment studies of industrial solid
      byproduct.

PMID- 18720949
TI  - Polysaccharide templated silver nanowire for ultrasensitive electrical detection
      of nucleic acids.
AB  - An ultrasensitive electrical detection method of nucleic acids has been developed
      on a nanogapped biosensor. In this study, peptide nucleic acid (PNA) probes were
      immobilized in the gaps of a pair of finger microelectrodes first and were then
      hybridized with their complementary target DNA. After that, pectin molecules were
      introduced into the DNA strand via zirconium-phosphate and zirconium-carbonate
      chemistries and were oxidated by periodate in acetate buffer (pH 3.98). The newly
      produced aldedyde groups act as a reactant to reduce ammoniacal silver ion to
      produce silver nanoparticles, which bridged the gap of the interdigitated
      microelectrode. The conductance of the metallic nanoparticles correlated directly
      with the amount of the hybridized DNA. A much higher sensitivity was achieved at
      3 femtomolar (S/N > 3) under optimal conditions. This biosensor is also
      applicable to the direct detection of RNA.

PMID- 18720950
TI  - Mixed ceria-based metal oxides biosensor for operation in oxygen restrictive
      environments.
AB  - The unique catalytic, electrochemical, and oxygen storage properties of ceria and
      mixed ceria/titania hybrid composites were used to fabricate a new type of
      electrochemical enzyme biosensor. These materials provided increased analytical
      performance and possibilities for operation in oxygen-free conditions of an
      oxidase enzyme biosensor using tyrosinase as a model example. The investigation
      of the enzymatic reaction in the presence and absence of oxygen was first carried
      out using cyclic voltammetry. The results were used to identify the role of each
      metal oxide in the immobilization matrix and fabricate a simple amperometric
      tyrosinase biosensor for the detection of phenol and dopamine. The biosensor was
      optimized and characterized with respect to response time, detection limit,
      linear concentration range, sensitivity, and kinetic parameters. The detection
      limit for phenol was in the nanomolar range, with a detection limit of 9.0 x 10(
      9) M and a sensitivity of 86 mA M(-1) in the presence of oxygen and of 5.6 x 10(
      9) M and a sensitivity of 65 mA M(-1) in the absence of oxygen. The optimized
      biosensor also showed selective determination of the neurotransmitter dopamine
      with a detection limit of 3.4 x 10(-8) M and a sensitivity of 14.9 mA M(-1) in
      the presence of oxygen and of 4.2 x 10(-8) M and 14.8 mA M(-1) in the absence of
      oxygen. This strategy shows promise for increasing the sensitivity of oxidase
      enzyme sensors and provides opportunities for operation in oxygen limited
      conditions. It can also be extended for the development of other enzyme
      biosensors.

PMID- 18720951
TI  - Noble-gas hydrides: new chemistry at low temperatures.
AB  - Noble-gas chemistry has been undergoing a renaissance in recent years, due in
      large part to noble-gas hydrides, HNgY, where Ng = noble-gas atom and Y =
      electronegative fragment. These molecules are exceptional because of their
      relatively weak bonding and large dipole moments, which lead to strongly enhanced
      effects of the environment, complexation, and reactions. In this Account, we
      discuss the matrix-isolation synthesis of noble-gas hydrides, their spectroscopic
      and structural properties, and their stabilities.This family of species was
      discovered in 1995 and now has 23 members that are prepared in noble-gas matrices
      (HXeBr, HKrCl, HXeH, HXeOH, HXeO, etc.). The preparations of the first neutral
      argon molecule, HArF, and halogen-free organic noble-gas molecules (HXeCCH,
      HXeCC, HKrCCH, etc.) are important highlights of the field. These molecules are
      formed by the neutral H + Ng + Y channel. The first addition reaction involving
      HNgY molecules was HXeCC + Xe + H --> HXeCCXeH, and this led to the first hydride
      with two noble-gas atoms (recently extended by HXeOXeH). The experimental
      synthesis of HNgY molecules starts with production of H and Y fragments in solid
      noble gas via the UV photolysis of suitable precursors. The HNgY molecules mainly
      form upon thermal mobilization of the fragments.One of the unusual properties of
      these molecules is the hindered rotation of some HNgY molecules in solid
      matrices; this has been theoretically modeled. HNgY molecules also have unusual
      solvation effects, and the H-Xe stretching mode shifts to higher frequencies (up
      to about 150 cm-1) upon interaction with other species.The noble hydrides have a
      new bonding motif: HNgY molecules can be represented in the form (H-Ng)+Y-, where
      (H-Ng)+ is mainly covalent, whereas the interaction between (HNg)+ and Y- is
      predominantly ionic. The HNgY molecules are highly metastable species
      representing high-energy materials. The decomposition process HNgY --> Ng + HY is
      always strongly exoergic; however, the decomposition is prevented by high
      barriers, for instance, about 2 eV for HXeCCH. The other decomposition channel
      HNgY --> H + Ng + Y is endothermic for all prepared molecules.Areas that appear
      promising for further study include the extension of argon chemistry, preparation
      of new bonds with noble-gas atoms (such as Xe-Si bond), and studies of radon
      compounds. The calculations suggest the existence of related polymers,
      aggregates, and even HNgY crystals, and their experimental preparation is a major
      challenge. Another interesting task, still in its early stages, is the
      preparation of HNgY molecules in the gas phase.

PMID- 18720953
TI  - Cryo-field emission scanning electron microscopy imaging of a rigid surfactant
      mesophase.
AB  - The aerosol OT/ L-alpha-phosphatidylcholine/isooctane/water system forms a rigid
      mesophase that transitions from reverse hexagonal to multilamellar in structure
      at specific water contents. This study shows that characteristics of ordered
      liquid-crystalline mesophases can be distinguished and imaged in high clarity
      using cryo-field emission scanning electron microscopy (cryo-FESEM). The reverse
      hexagonal phase consists of bundles of long cylinders, some with length scales of
      over 2 microm, that are randomly oriented as part of a larger domain. Cryo
      imaging allows the visualization of the intercylinder spacings and the details of
      transitions from one domain to another. The multilamellar structured mesophase
      consists of spherical vesicles of 100 nm to 10 microm in diameter, with
      intervening noncrystalline isotropic regions. Coexistence regions containing both
      the reverse hexagonal and lamellar structures are also observed in the transition
      from the reverse hexagonal to the lamellar phase. These results complement and
      qualitatively verify our earlier studies with small-angle neutron scattering,
      high-field nuclear magnetic resonance spectroscopy, and freeze-fracture direct
      imaging transmission electron microscopy. The information is useful in
      understanding materials templating in these rigid systems.

PMID- 18720954
TI  - Chemical conversion synthesis and optical properties of metal sulfide hollow
      microspheres.
AB  - A facile chemical conversion method has been demonstrated to prepare various
      metal sulfide hollow microspheres. The present strategy utilizes the large
      difference in solubility between ZnS and other metal sulfides (Ag2S, PbS, CuS,
      Cu2S, Bi2S3, and Sb2S3) for the effective transformation and shows mild growth
      conditions and good reproducibility. The morphology, structure, and composition
      of the yielded hollow nanostructures have been confirmed by transmission electron
      microscopy, energy-dispersive X-ray analysis, and X-ray diffraction measurements.
      The optical properties of the metal sulfide hollow microspheres have been
      systematically investigated by absorption, micro-Raman, and photoluminescence
      spectroscopy. The results demonstrate that these metal sulfide hollow
      microspheres possess good optical quality with tunable band gaps and luminescence
      properties, which indicate their broad potential applications. This simple
      chemical conversion technique can be further extended to the synthesis of other
      semiconductors with various morphologies.

PMID- 18720952
TI  - The pursuit of a scalable nanofabrication platform for use in material and life
      science applications.
AB  - In this Account, we describe the use of perfluoropolyether (PFPE)-based materials
      that are able to accurately mold and replicate micro- and nanosized features
      using traditional techniques such as embossing as well as new techniques that we
      developed to exploit the exceptional surface characteristics of fluorinated
      substrates. Because of the unique partial wetting and nonwetting characteristics
      of PFPEs, we were able to go beyond the usual molding and imprint lithography
      approaches and have created a technique called PRINT (Particle [or Pattern]
      Replication In Nonwetting Templates). PRINT is a distinctive "top-down"
      fabrication technique capable of generating isolated particles, arrays of
      particles, and arrays of patterned features for a plethora of applications in
      both nanomedicine and materials science. A particular strength of the PRINT
      technology is the high-resolution molding of well-defined particles with precise
      control over size, shape, deformability, and surface chemistry. The level of
      replication obtained showcases some of the unique characteristics of PFPE molding
      materials. In particular, these materials arise from very low surface energy
      precursors with positive spreading coefficients, can be photocured at ambient
      temperature, and are minimally adhesive, nonswelling, and conformable. These
      distinctive features enable the molding of materials with unique attributes and
      nanometer resolution that have unprecedented scientific and technological value.
      For example, in nanomedicine, the use of PFPE materials with the PRINT technique
      allows us to design particles in which we can tailor key therapeutic parameters
      such as bioavailability, biodistribution, target-specific cell penetration, and
      controlled cargo release. Similarly, in materials science, we can fabricate
      optical films and lens arrays, replicate complex, naturally occurring objects
      such as adenovirus particles, and create 2D patterned arrays of inorganic oxides.

PMID- 18720955
TI  - Liquid crystal codendrimers with a statistical distribution of phenolic and
      mesogenic groups: behavior as Langmuir and Langmuir-Blodgett films.
AB  - The first series of carbosilane liquid crystal codendrimers with groups of
      different polarity has been synthesized. The chemical structure of the newly
      synthesized materials and the composition of the codendrimers were studied by NMR
      spectroscopy and MALDI-TOF MS. It was found that the codendrimers tend to form
      stable Langmuir films at the air-water surface. The influence of composition and
      generation number on surface pressure-surface area isotherms and film stability
      was studied. Brewster angle microscopy confirmed the different phase behavior for
      monolayers of different codendrimer composition and generation number. It was
      found that side groups of fifth-generation codendrimers do not segregate, unlike
      those of lower generations. Langmuir-Blodgett films on solid substrates were
      obtained by the vertical dipping method. X-ray diffraction showed that the
      codendrimers with 75% of hydrophobic mesogenic terminal groups formed ordered
      layers parallel to the substrate.

PMID- 18720956
TI  - Surface modification of polymeric vesicles via host-guest inclusion complexation.
AB  - We have prepared a novel kind of building block (CD-PI-CD) of polyether imide
      (PI) with beta-cyclodextrin (beta-CD) at the both ends that self-assembles into
      vesicles in water. The vesicles are "reactive" in supramolecular chemistry
      because the host groups of beta-CD equally distribute on the inside and outside
      surfaces of the vesicles. Isothermal titration calorimetry (ITC) and static light
      scattering (SLS) studies demonstrate that both the inner and outer surfaces of
      the vesicles can be further modified noncovalently with adamantane-ended
      polyethlene glycol (Ada-PEG) via a host-guest inclusion interaction between beta
      CD and adamantane.

PMID- 18720957
TI  - Anisotropic island growth: a new approach to thin film electrocrystallization.
AB  - The electrochemical deposition of metals onto foreign substrates usually occurs
      through Volmer-Weber island growth, and hence the structure and properties of
      thin films are critically dependent on the mechanism of nucleation and growth.
      For example, high nucleus densities are essential for achieving island
      coalescence at small thickness. Here we demonstrate a new approach to controlling
      thin film microstructure through the control of island geometry. By promoting
      anisotropic island growth, film coalescence can be achieved at smaller thickness
      and with lower island densities.

PMID- 18720958
TI  - Si(111) surface modified with alpha,beta-unsaturated carboxyl groups studied by
      MIR-FTIR.
AB  - A Si(111) surface modified with alpha,beta-unsaturated carboxyl groups was
      fabricated using activated alkynes such as propiolic acid and propiolic acid
      methyl ester via hydrosilylation reaction. The obtained coverage of carboxyl
      groups was roughly estimated to be 55-60% in both cases from the Si-2p and C-1s X
      ray photoelectron specroscopy (XPS) peak intensities. The detailed surface
      structures were investigated by multiple internal reflection Fourier transform
      infrared (MIR-FTIR) measurement. It was revealed that this reaction was promoted
      by visible light irradiation at room temperature. The Si surface modified with
      functional groups prepared under such a moderate condition is adaptable to
      functional devices which are easily damaged under UV irradiation or high
      temperature conditions.

PMID- 18720959
TI  - Temperature-sensitive nonionic vesicles prepared from Span 80 (sorbitan
      monooleate).
AB  - Different types of nonionic vesicles were prepared from commercial Span 80 (also
      called sorbitan monooleate), as an inexpensive, biocompatible alternative to
      conventional phospholipid-based vesicles (liposomes). The vesicles were
      characterized by different techniques and comparison was made with vesicles
      formed from POPC (1-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine) or DOPC (1,2
      dioleoyl- sn-glycero-3-phosphocholine). Dynamic light scattering measurements,
      electron microscopy analyses, and two types of fusion assays indicate that Span
      80 vesicles are stable for at least 7 days at 4 or 25 degrees C, while storage at
      42 degrees C causes irreversible vesicle fusion. This indicates that Span 80
      vesicles are thermoresponsive with vesicle fusion occurring at elevated
      temperature. This property may be related to headgroup dehydration and is
      certainly not directly linked to the phase transition temperature (Tm) of the
      vesicles, since the Tm is below -30 degrees C, as determined by differential
      scanning calorimetry (DSC). The measured Tm value for Span 80 vesicles is lower
      than in the case of DOPC or POPC, correlating with a higher fluidity of Span 80
      vesicles as compared to POPC or DOPC vesicles, as determined with DPH (1,6
      diphenyl-1,3,5-hexatriene) as fluorescent membrane probe. High fluidity
      correlates with increased leakage of entrapped water-soluble dye molecules.
      Addition of cholesterol and soybean phosphatidylcholine lowers the extent of
      leakage, allowing a tuning of the bilayer permeability.

PMID- 18720960
TI  - Spontaneous vesicle formation in catanionic mixtures of amino acid-based
      surfactants: chain length symmetry effects.
AB  - The use of amino acids for the synthesis of novel surfactants with vesicle
      forming properties potentially enhances the biocompatibility levels needed for a
      viable alternative to conventional lipid vesicles. In this work, the formation
      and characterization of catanionic vesicles by newly synthesized lysine- and
      serine-derived surfactants have been investigated by means of phase behavior
      mapping and PFG-NMR diffusometry and cryo-TEM methods. The lysine-derived
      surfactants are double-chained anionic molecules bearing a pseudogemini
      configuration, whereas the serine-derived amphiphile is cationic and single
      chained. Vesicles form in the cationic-rich side for narrow mixing ratios of the
      two amphiphiles. Two pairs of systems were studied: one symmetric with equal
      chain lengths, 2C12/C12, and the other highly asymmetric with 2C8/C16 chains,
      where the serine-based surfactant has the longest chain. Different mechanisms of
      the vesicle-to-micelle transition were found, depending on symmetry: the 2C12/C12
      system entails limited micellar growth and intermediate phase separation, whereas
      the 2C8/C16 system shows a continuous transition involving large wormlike
      micelles. The results are interpreted on the basis of currently available models
      for the micelle-vesicle transitions and the stabilization of catanionic vesicles
      (energy of curvature vs mixing entropy).

PMID- 18720961
TI  - Motion of drops on a surface induced by thermal gradient and vibration.
AB  - It is well known that a liquid drop with a low contact angle (approximately 45
      degrees ) and low wetting hysteresis moves toward the colder region of a
      temperature gradient substrate as a result of the thermal Marangoni force. A
      moderately sized water drop, however, usually does not move on such a surface
      because of the overwhelming effect of hysteresis. The water drop can, however, be
      forced to move when it is vibrated on a temperature gradient surface with its
      velocity exhibiting maxima at the respective Rayleigh frequencies. A simple model
      is presented that captures the dependence of drop velocity on hysteresis,
      vibration amplitude, and the forcing and resonance frequencies of vibration.

PMID- 18720962
TI  - Aqueous surfactant two-phase systems in a mixture of cationic gemini and anionic
      surfactants.
AB  - The phase behavior as well as the microstructures of the cationic gemini
      surfactant and anionic conventional surfactant aqueous two-phase system (ASTP)
      have been studied. The ASTP formation can be attributed to the coexistence of
      different kinds of aggregates in the upper and lower phases. The effects of
      temperature, shearing, surfactant concentration and mixing molar ratio on the
      phase separation of the ASTP-forming systems are systematically investigated. The
      ASTP can be destroyed by applying shear and increasing temperature. In this
      process, the lamellar structures (flat bilayers) in the ASTP are transformed into
      vesicles. Variation of surfactant structure also affects the phase behavior and
      the aggregates transformation. Appropriate molecular packing is crucial for the
      formation of ASTP.

PMID- 18720963
TI  - New semifluorinated dithiols self-assembled monolayers on a copper platform.
AB  - New alpha,omega-semifluorinated dithiols HS-(CH2)11-(CF2)n-(CH2)11-SH, called
      DTn, and corresponding dithioacetate molecules CH3COS-(CH2)11-(CF2)n-(CH2)11
      SCOCH3, called DTAn ( n = 4, 6, 8), were synthesized and used to create self
      assembled monolayers (SAMs) on both untreated copper surfaces and
      electrochemically reduced ones. The aim of this study is to assess the
      organization of the resulting SAMs, particularly the effect of the presence of
      two perhydrogenated segments surrounding the perfluorinated one, and the ability
      of these difunctional molecules to bind copper substrates by only one end per
      molecule. In each case, the organization of the SAM is rather poor and only DTA8
      molecules seem to adopt an upright position on reduced copper. In addition, the
      layers have been investigated by cyclic voltammetry (CV) to assess their
      coverage. DT4 SAMs reveal a covering ratio higher than 99%.

PMID- 18720964
TI  - Defect induced asymmetric pit formation on hydroxyapatite.
AB  - Defect sites on bone minerals play a critical role in bone remodeling processes.
      We investigated single crystal hydroxyapatite (100) surfaces bearing crystal
      defects under acidic dissolution conditions using real-time in situ atomic force
      microscopy. At defect sites, surface structure-dependent asymmetric hexagonal
      etch pits were formed, which dominated the overall dissolution rate. Meanwhile,
      dissolution from the flat terraces proceeded by stochastic formation of flat
      bottom etch pits. The resulting pit shapes were intrinsically dictated by the HAP
      crystal structure. Computational modeling also predicted different step energies
      associated with different facets of the asymmetric etch pits. Our microscopic
      observations of HAP dissolution are significant for understanding the effects of
      local surface structure on the bone mineral remodeling process and provide useful
      insights for the design of novel therapies for treating osteoporosis and dental
      caries.

PMID- 18720965
TI  - Superhydrophobic composite films produced on various substrates.
AB  - Hydrophilic silica (SiO2) nanoparticles were dispersed in solutions of
      poly(methyl methacrylate) (PMMA) and in solutions of a commercial poly(alkyl
      siloxane) (Rhodorsil 224), and the suspensions were sprayed on glass surfaces.
      The effect of the particle concentration on the hydrophobic character of PMMA
      SiO2 and Rhodorsil-SiO2 films was investigated and showed the following: (i)
      Static contact angles (theta s), measured on surfaces that were prepared from
      dilute dispersions (particle concentration <1% w/v), increase rapidly with
      particle concentration and reach maximum values (154 and 164 degrees for PMMA
      SiO2 and siloxane-SiO2, respectively). Further increases in particle
      concentration do not have any effect on theta s. (ii) The effect of particle
      concentration on the contact angle hysteresis (thetaAlpha - thetaR) is more
      complicated: as the particle concentration increases, we first notice an increase
      in hysteresis, which then decreases and finally becomes constant at elevated
      particle concentrations. The lowest thetaAlpha - thetaR values were 5 degrees for
      PMMA-SiO2 and 3 degrees for siloxane-SiO2, respectively. (iii) SEM and AFM images
      show that a two-length-scale hierarchical structure is formed on the surface of
      the superhydrophobic films. It is demonstrated that superhydrophobicity can be
      achieved using various hydrophilic nanoparticles (alumina and tin oxide
      nanoparticles were successfully tested) and that the substrate has almost no
      effect on the hydrophobic character of the applied coatings, which were produced
      on silicon, concrete, aluminum, silk, wood, marble, and of course glass. The
      results are discussed in light of Wenzel and Cassie-Baxter models.

PMID- 18720966
TI  - Physical nature of intermolecular interactions within cAMP-dependent protein
      kinase active site: differential transition state stabilization in phosphoryl
      transfer reaction.
AB  - The origin of enzyme catalytic activity may be effectively explored within the
      nonempirical theory of intermolecular interactions. The knowledge of
      electrostatic, exchange, delocalization, and correlation components of the
      transition state and substrates stabilization energy arising from each enzyme
      active site residue allows to examine the most essential physical effects
      involved in enzymatic catalysis. Consequently, one can build approximate models
      of the catalytic activity in a systematic and legitimate manner. Whenever the
      dominant role of electrostatic interactions is recognized or assumed, the
      properties of an optimal catalytic environment could be simply generalized and
      visualized by means of catalytic fields that, in turn, aids the design of new
      catalysts. Differential transition state stabilization (DTSS) methodology has
      been applied herein to the phosphoryl transfer reaction catalyzed by cAMP
      dependent protein kinase (PKA). The MP2 results correlate well with the available
      experimental data and theoretical findings indicating that Lys72, Asp166, and the
      two magnesium ions contribute -22.7, -13.3, -32.4, and -15.2 kcal/mol to
      differential transition state stabilization, respectively. Although all
      interaction energy components except that of electron correlation contribution
      are meaningful, the first-order electrostatic term correlates perfectly with MP2
      catalytic activity. Catalytic field technique was also employed to visualize
      crucial electrostatic features of an ideal catalyst and to compare the latter
      with the environment provided by PKA active site. The map of regional electronic
      chemical potential was used to analyze the unfavorable catalytic effect of
      Lys168. It was found that locally induced polarization of TS atoms
      thermodynamically destabilizes electrons, pulling them to regions displaying
      higher electronic chemical potential.

PMID- 18720967
TI  - Workman-Reynolds freezing potential measurements between ice and dilute salt
      solutions for single ice crystal faces.
AB  - Workman-Reynolds freezing potentials have been measured for the first time across
      the interface between single crystals of ice 1h and dilute electrolyte solutions.
      The measured electric potential is a strictly nonequilibrium phenomenon and a
      function of the concentration of salt, freezing rate, orientation of the ice
      crystal, and time. When all these factors are controlled, the voltage is
      reproducible to the extent expected with ice growth experiments. Zero voltage is
      obtained with no growth or melting. For rapidly grown ice 1h basal plane in
      contact with a solution of 10 (-4) M NaCl the maximum voltage exceeds 30 V and
      decreases to zero at both high and low salt concentrations. These single-crystal
      experiments explain much of the data captured on this remarkable phenomenon since
      1948.

PMID- 18720968
TI  - Intermolecular cycloaddition of N-boranonitrone with alkenes.
AB  - Ethyl glyoxylate O-tert-butyldimethylsilyloxime (8), on treatment with 2.2 equiv
      of BF3 x OEt2, generated N-boranonitrone E, which underwent intermolecular
      cycloaddition with alkenes 18 to afford isoxazolidines 19 in moderate to high
      yields. The cycloaddition of N-boranonitrone E with most of the alkenes gave 3,5
      trans isoxazolidines as the major isomers via a concerted mechanism. However, in
      the case of 1-methylated cyclic alkenes (18j and 18l), the cycloaddition
      surprisingly furnished the 3,3a-cis-cycloadducts (19j and 19l) as major isomers.
      A possible explanation is that the reaction of 1-methylated cyclic alkenes
      proceeds mainly via a stepwise mechanism. This reaction of terminal alkenes is
      very useful for synthesis of 1,3-anti aminoalcohol derivatives by reductive
      cleavage of an N-O bond.

PMID- 18720969
TI  - Arylation and vinylation of alkenes based on unusual sequential semipinacol
      rearrangement/Grob fragmentation of allylic alcohols.
AB  - Alkenes can be stereoselectively arylated and vinylated without transition-metal
      catalyst under mild conditions through an interesting NBS-promoted semipinacol
      rearrangement and a subsequent unusual NaOH-mediated Grob fragmentation.

PMID- 18720970
TI  - Palladium-catalyzed carbonylation reactions of aryl bromides at atmospheric
      pressure: a general system based on Xantphos.
AB  - A method for the Pd-catalyzed carbonylation of aryl bromides has been developed
      using Xantphos as the ligand. This method is effective for the direct synthesis
      of Weinreb amides, primary and secondary benzamides, and methyl esters from the
      corresponding aryl bromides at atmospheric pressure. In addition, a putative
      catalytic intermediate, (Xanphos)Pd(Br)benzoyl, was prepared and an X-ray crystal
      structure was obtained revealing an unusual cis-coordination mode of Xantphos in
      this palladium-acyl complex.

PMID- 18720971
TI  - Bioactive asterric acid derivatives from the Antarctic ascomycete fungus Geomyces
      sp.
AB  - Five new asterric acid derivatives, ethyl asterrate (3), n-butyl asterrate (4),
      and geomycins A-C (6-8), have been isolated from cultures of an isolate of the
      Antarctic ascomycete fungus Geomyces sp. The structures of these metabolites were
      elucidated by NMR spectroscopy. The absolute configuration of 8 was determined by
      application of the CD excitation chirality method. Compound 7 displayed
      antifungal activity against Aspergillus fumigatus, whereas 8 showed antimicrobial
      activities against gram-positive and gram-negative bacteria.

PMID- 18720972
TI  - Nanoscale fluid transport: size and rate effects.
AB  - The transport behavior of water molecules inside a model carbon nanotube is
      investigated by using nonequilibrium molecular dynamcis (NMED) simulations. The
      shearing stress between the nanotube wall and the water molecules is identified
      as a key factor in determining the nanofluidic properties. Due to the effect of
      nanoscale confinement, the effective shearing stress is not only size sensitive
      but also strongly dependent on the fluid flow rate. Consequently, the nominal
      viscosity of the confined water decreases rapidly as the tube radius is reduced
      or when a faster flow rate is maintained. An infiltration experiment on a
      nanoporous carbon is performed to qualitatively validate these findings.

PMID- 18720974
TI  - Phase transition and compressibility in silicon nanowires.
AB  - Silicon nanowires (Si NWs), one-dimensional single crystalline, have recently
      drawn extensive attention, thanks to their robust applications in electrical and
      optical devices as well as in the strengthening of diamond/SiC superhard
      composites. Here, we conducted high-pressure synchrotron diffraction experiments
      in a diamond anvil cell to study phase transitions and compressibility of Si NWs.
      Our results revealed that the onset pressure for the Si I-II transformation in Si
      NWs is approximately 2.0 GPa lower than previously determined values for bulk Si,
      a trend that is consistent with the analysis of misfit in strain energy. The bulk
      modulus of Si-I NWs derived from the pressure-volume measurements is 123 GPa,
      which is comparable to that of Si-V NWs but 25% larger than the reported values
      for bulk silicon. The reduced compressibility in Si NWs indicates that the unique
      wire-like structure in nanoscale plays vital roles in the elastic behavior of
      condensed matter.

PMID- 18720973
TI  - Quantitative and label-free technique for measuring protease activity and
      inhibition using a microfluidic cantilever array.
AB  - We report the use of a SiN x based gold coated microcantilever array to
      quantitatively measure the activity and inhibition of a model protease
      immobilized on its surface. Trypsin was covalently bound to the gold surface of
      the microcantilever using a synthetic spacer, and the remaining exposed silicon
      nitride surface was passivated with silanated polyethylene glycol. The nanoscale
      cantilever motions induced by trypsin during substrate turnover were
      quantitatively measured using an optical laser-deflection technique. These
      microcantilever deflections directly correlated with the degree of protease
      turnover of excess synthetic fibronectin substrate ( K M = 0.58 x 10 (-6) M).
      Inhibition of surface-immobilized trypsin by soybean trypsin inhibitor (SBTI) was
      also observed using this system.

PMID- 18720975
TI  - Electron beam supercollimation in graphene superlattices.
AB  - Although electrons and photons are intrinsically different, importing useful
      concepts in optics to electronics performing similar functions has been actively
      pursued over the last two decades. In particular, collimation of an electron beam
      is a long-standing goal. We show that ballistic propagation of an electron beam
      with virtual no spatial spreading or diffraction, without a waveguide or external
      magnetic field, can be achieved in graphene under an appropriate class of
      experimentally feasible one-dimensional external periodic potentials. The novel
      chiral quasi-one-dimensional metallic state that the charge carriers are in
      originates from a collapse of the intrinsic helical nature of the charge carriers
      in graphene owing to the superlattice potential. Beyond providing a new way to
      constructing chiral one-dimensional states in two dimensions, our findings should
      be useful in graphene-based electronic devices (e.g., for information processing)
      utilizing some of the highly developed concepts in optics.

PMID- 18720976
TI  - Plasmonic nearfield scanning probe with high transmission.
AB  - Nearfield scanning optical microscopy (NSOM) offers a practical means of optical
      imaging, optical sensing, and nanolithography at a resolution below the
      diffraction limit of the light. However, its applications are limited due to the
      strong attenuation of the light transmitted through the subwavelength aperture.
      To solve this problem, we report the development of plasmonic nearfield scanning
      optical microscope with an efficient nearfield focusing. By exciting surface
      plasmons, plasmonic NSOM probes are capable of confining light into a 100 nm
      spot. We show by nearfield lithography experiments that the intensity at the near
      field is at least one order stronger than the intensity obtained from the
      conventional NSOM probes under the same illumination condition. Such a high
      efficiency can enable plasmonic NSOM as a practical tool for nearfield
      lithography, data storage, cellular visualization, and many other applications
      requiring efficient transmission with high resolution.

PMID- 18720977
TI  - Fabrication of surface plasmon resonators by nanoskiving single-crystalline gold
      microplates.
AB  - This paper demonstrates the sectioning of chemically synthesized, single
      crystalline microplates of gold with an ultramicrotome (nanoskiving) to produce
      single-crystalline nanowires; these nanowires act as low-loss surface plasmon
      resonators. This method produces collinearly aligned nanostructures with small,
      regular changes in dimension with each consecutive cross-section: a single
      microplate thus can produce a number of "quasi-copies" (delicately modulated
      variations) of a nanowire. The diamond knife cuts cleanly through microplates 35
      microm in diameter and 100 nm thick without bending the resulting nanowire and
      cuts through the sharp edges of a crystal without deformation to generate
      nanoscale tips. This paper compares the influence of sharp tips and blunt tips on
      the resonator modes in these nanowires.

PMID- 18720978
TI  - Quantitative optical trapping of single gold nanorods.
AB  - We report a quantitative analysis of the forces acting on optically trapped
      single gold nanorods. Individual nanorods with diameters between 8 and 44 nm and
      aspect ratios between 1.7 and 5.6 were stably trapped in three dimensions using a
      laser wavelength exceeding their plasmon resonance wavelengths. The interaction
      between the electromagnetic field of an optical trap and a single gold nanorod
      correlated with particle polarizability, which is a function of both particle
      volume and aspect ratio.

PMID- 18720979
TI  - Nanostructured metal film with asymmetric optical transmission.
AB  - We demonstrate for the first time a nanostructured planar photonic metamaterial
      transmitting light differently in forward and backward directions.

PMID- 18720980
TI  - DNA binding and cleaving activity of the new cleft molecule N,N'
      Bis(guanidinoethyl)-2,6-pyridinedicarboxamide in the absence or in the presence
      of copper(II).
AB  - Novel cleft molecule pyridine-2,6-dicarboxamide appending two guanidinoethyl
      group side arms (Gua) was synthesized. The interactions of the cleft molecule in
      the absence of copper(II) (Gua) or in the presence of copper(II) (Cu2+-Gua) with
      calf thymus DNA were studied by fluorescence and CD spectroscopy. The results
      indicate that the DNA binding affinity of Cu2+-Gua is stronger than that of Gua,
      and the binding constants of Cu2+-Gua and Gua are 1.61 x 10(6) M(-1) and 2.86 x
      10(5) M(-1), respectively. Agarose gel electrophoresis was used to assess the
      plasmid pUC 19 DNA cleavage activities in the presence of Gua and Cu2+-Gua.
      Kinetic data of DNA cleavage promoted by Cu2+-Gua under physiological conditions
      fit a saturation kinetic profile with k(max) of 0.0173 +/- 0.0011 h(-1), which
      gave a aproximately 10(6)-fold rate acceleration over uncatalyzed supercoiled
      DNA, while the catalyst concentration is lower than 0.0625 mM. The hydrolysis
      pathway was proposed as the possible mechanism for DNA cleavage promoted by Cu2+
      Gua. The acceleration is due to efficient cooperative catalysis of the copper
      cation center and the functional groups (bis(guanidinium) groups).

PMID- 18720981
TI  - Rapid and efficient production of radiolabeled antibody conjugates using vacuum
      diafiltration guided by mathematical modeling.
AB  - Increasing interest in the use of radiolabeled antibodies for cancer imaging and
      therapy drives the need for more efficient production of the antibody conjugates.
      Here, we illustrate a method for rapid and efficient production of radiolabeled
      antibody conjugates using vacuum diafiltration guided by mathematical modeling.
      We apply this technique to the production of 1,4,7,10-tetraazacyclododecane
      1,4,7,10-tetraacetic acid (DOTA)-conjugated antibodies at the milligram and gram
      production scale and achieve radiolabeling efficiencies >95% using In-111. Using
      vacuum diafiltration, antibody-chelate conjugation and purification can be
      accomplished within the same vessel, and the entire process can be completed in
      <24 h. Vacuum diafiltration also offers safer and gentler processing conditions
      by eliminating the need to keep the retentate vessel under positive pressure
      through applied gas pressure or shear-inducing restriction points in the
      retentate flow path. Experimental data and mathematical model calculations
      suggest there exists a weak binding affinity (approximately 10(4)M(-1)) between
      the charged chelate molecules (e.g., DOTA) and the antibodies that slows the
      removal of excess chelate during purification. By analyzing the radiolabeling
      efficiency as a function of the number of diavolumes, we demonstrate the
      importance of balancing the removal of free chelate with the introduction of
      metal contaminants from the diafiltration buffer and also illustrate how to
      optimize radiolabeling of antibody conjugates under a variety of operating
      conditions. This methodology is applicable to the production of antibody
      conjugates in general.

PMID- 18720983
TI  - Heme transport and detoxification in nematodes: subproteomics evidence of
      differential role of glutathione transferases.
AB  - In contrast to their mammalian hosts, parasitic nematodes are heme auxotrophs and
      require pathways for the uptake and transport of exogenous heme for incorporation
      into hemoproteins. Phase II detoxification Nu-class glutathione transferase (GST)
      proteins have a proposed role as heme-binding ligandins in parasitic nematodes.
      The genome-verified free-living nematode Caenorhabditis elegans also cannot
      synthesize heme and is an ideal functional genomics model to delineate the role
      of individual nematode GSTs in heme trafficking and heme detoxification. In this
      study, C. elegans was exposed to externally controlled heme concentrations
      ranging from 20-fold suboptimal growth levels to 10-fold supra-optimal growth
      levels to mimic fluctuations in blood- and tissue-feeding parasitic cousins from
      the same nematode group. A new heme-responsive GST (GST-19) was identified by
      subproteomics approaches. Functional characterization of this and two other C.
      elegans GSTs revealed that they all have high affinity for heme compounds similar
      to mammalian soluble heme carrier proteins such as HBP23 ( K d approximately 10 (
      8) M). In the genomics-predicted absence of orthologous mammalian soluble heme
      binding proteins in nematodes, we propose that Nu-class GSTs are candidates in
      the cellular processing of heme compounds. Toxic heme binding may be coupled to
      enzymatic protection from its breakdown as several GSTs possess glutathione
      peroxidase activity.

PMID- 18720982
TI  - Comprehensive characterization of heat shock protein 27 phosphorylation in human
      endothelial cells stimulated by the microbial dithiole thiolutin.
AB  - Thiolutin is a sulfur-based microbial compound with known activity as an
      angiogenesis inhibitor. Relative to previously studied angiogenesis inhibitors,
      thiolutin is a remarkably potent inducer of heat shock protein 27 (Hsp27)
      phosphorylation. This phosphorylation requires p38 kinase but is independent of
      increased p38 phosphorylation. To elucidate how thiolutin regulates Hsp27
      phosphorylation and ultimately angiogenesis, Hsp27 was immunoprecipitated using
      nonphosphorylated and phospho-Ser78 specific antibodies from lysates of thiolutin
      treated and untreated human umbilical vein endothelial cells and analyzed by LC
      MS. Separate LC-MS analyses of Lys-C, Lys-C plus trypsin, and Lys-C plus Glu-C
      digests provided 100% sequence coverage, including the identification of a very
      large 13 kDa Lys-C fragment using a special sample handling procedure (4 M
      guanidine HCl) prior to the LC-MS analysis to improve the large peptide recovery.
      The analysis revealed a novel post-translational modification of Hsp27 involving
      truncation of the N-terminal Met and acetylation of the penultimate Thr. Analysis
      of a Glu-C fragment containing two phosphorylation sites, Ser78 and Ser82, and a
      tryptic fragment containing the other phosphorylation site, Ser15, enabled
      quantitative stoichiometry of Hsp27 phosphorylation by LC-MS. The strategy
      revealed details of Hsp27 phosphorylation, including significant di
      phosphorylation at both Ser78 and Ser82, that would be difficult to obtain by
      traditional approaches because oligomerization of the hydrophobic N-terminal
      region of the molecule prevents efficient enzymatic cleavage. The combination of
      Western blotting, immunoprecipation, and LC-MS provides a quantitative analysis
      of thiolutin-stimulated Hsp27 phosphorylation and further defines the role of
      Hsp27 in the antiangiogenic activities of thiolutin and related dithiolethiones.

PMID- 18720984
TI  - Discovery of potent and selective small-molecule PAR-2 agonists.
AB  - Proteinase activated receptor-2 plays a crucial role in a wide variety of
      conditions with a strong inflammatory component. We present the discovery and
      characterization of two structurally different, potent, selective, and
      metabolically stable small-molecule PAR-2 agonists. These ligands may be useful
      as pharmacological tools for elucidating the complex physiological role of the
      PAR-2 receptors as well as for the development of PAR-2 antagonists.

PMID- 18720985
TI  - Gas-phase protonation thermochemistry of adenosine.
AB  - The goal of this work was to obtain a detailed insight on the gas-phase
      protonation energetic of adenosine using both mass spectrometric experiments and
      quantum chemical calculations. The experimental approach used the extended
      kinetic method with nanoelectrospray ionization and collision-induced
      dissociation tandem mass spectrometry. This method provides experimental values
      for proton affinity, PA(adenosine) = 979 +/- 1 kJ.mol (-1), and for the
      "protonation entropy", Delta p S degrees (adenosine) = S degrees (adenosineH +) -
      S degrees (adenosine) = -5 +/- 5 J.mol (-1).K (-1). The corresponding gas-phase
      basicity is consequently equal to: GB(adenosine) = 945 +/- 2 kJ.mol (-1) at 298K.
      Theoretical calculations conducted at the B3LYP/6-311+G(3df,2p)//B3LYP/6
      31+G(d,p) level, including 298 K enthalpy correction, predict a proton affinity
      value of 974 kJ.mol (-1) after consideration of isodesmic proton transfer
      reactions with pyridine as the reference base. Moreover, computations clearly
      showed that N3 is the most favorable protonation site for adenosine, due to a
      strong internal hydrogen bond involving the hydroxyl group at the 2' position of
      the ribose sugar moiety, unlike observations for adenine and 2'-deoxyadenosine,
      where protonation occurs on N1. The existence of negligible protonation entropy
      is confirmed by calculations (theoretical Delta p S degrees (adenosine)
      approximately -2/-3 J.mol (-1).K (-1)) including conformational analysis and
      entropy of hindered rotations. Thus, the calculated protonation thermochemical
      properties are in good agreement with our experimental measurements. It may be
      noted that the new PA value is approximately 10 kJ.mol (-1) lower than the one
      reported in the National Institute of Standards and Technology (NIST) database,
      thus pointing to a correction of the tabulated protonation thermochemistry of
      adenosine.

PMID- 18720986
TI  - meso-(4-(N,N-dialkylamino)phenyl)-substituted subporphyrins: remarkably perturbed
      absorption spectra and enhanced fluorescence by intramolecular charge transfer
      interactions.
AB  - A series of meso-(4-(N,N-dibenzylamino)phenyl)-substituted subporphyrins was
      synthesized by means of Buchwald-Hartwig amination protocol. Substitution of the
      amino group at the 4-position of the meso-phenyl substituent resulted in a
      remarkable red shift in the absorption spectra and drastic enhancement of
      fluorescence intensity probably as a consequence of intramolecular CT
      interaction. These characteristics have been utilized to construct a cation
      sensing system by appending a 1-aza-15-crown-5 unit to subporphyrin that displays
      large spectral changes upon cation binding.

PMID- 18720987
TI  - Short synthesis of (-)-cephalotaxine using a radical cascade.
AB  - The short total synthesis of (-)-cephalotaxine is described. The concise
      construction of the pentacyclic core of this alkaloid was achieved by a radical
      cascade involving 7-endo and 5-endo cyclizations.

PMID- 18720988
TI  - Stereoselective direct copper-catalyzed alkenylation of oxazoles with
      bromoalkenes.
AB  - A copper-catalyzed direct alkenylation of oxazoles with bromoalkenes has been
      developed. The method is both regio- and stereoselective and tolerates a variety
      of functional groups. A wide range of 2-E-vinyl-substituted oxazoles were
      obtained in high yields including the highly fluorescent alkaloid annuloline.

PMID- 18720989
TI  - Interrupting the Nazarov cyclization with indoles.
AB  - A carbon-terminated interrupted Nazarov reaction is described. The trimethylsilyl
      enol ethers derived from propargyl vinyl ketones undergo selective proton
      transfer at the distal acetylenic carbon atom to provide allenyl vinyl ketones as
      transient intermediates. In the presence of indoles, a cascade of reactions is
      initiated that converts the initially formed pentadienyl cations to
      cyclopentenones bearing a quaternary alpha carbon atom.

PMID- 18720990
TI  - Synthesis and columnar mesophase of fluorescent liquid crystals bearing a C2
      symmetric chiral core.
AB  - A chiral and fluorescent columnar mesogen prepared from chiral binaphthols is
      reported. This liquid crystal comprises a C2-symmetric chiral core with two
      staggered aromatic planes. Its hexagonal columnar (Col(h)) mesophase was
      characterized by appropriate physical methods.

PMID- 18720991
TI  - Selective monolithiation of dibromobiaryls using microflow systems.
AB  - Selective monolithiation of dibromobiaryls, such as 2,2'-dibromobiphenyl, 4,4'
      dibromobiphenyl, 2,7-dibromo-9,9-dioctylfluorene, 2,2'-dibromo-1,1'-binaphthyl,
      and 5,5'-dibromo-2,2'-bithiophene, with 1 equiv of n-butyllithium followed by the
      reaction with electrophiles was achieved using a microflow system by virtue of
      fast micromixing and precise temperature control. Sequential introduction of two
      different electrophiles based on this method was also achieved using a microflow
      system composed of four micromixers and four microtube reactors.

PMID- 18720992
TI  - Carbonylation of aryl chlorides with oxygen nucleophiles at atmospheric pressure.
      Preparation of phenyl esters as acyl transfer agents and the direct preparation
      of alkyl esters and carboxylic acids.
AB  - A mild, functional group tolerant method of the preparation of phenyl esters from
      aryl chlorides via palladium-catalyzed carbonylation is described using
      atmospheric pressure of carbon monoxide. Phenyl esters are shown to be useful
      acylating agents, delivering libraries of carbonyl derivatives, including alkyl,
      allyl and thioesters, under very mild conditions. Direct preparation of alkyl
      esters and carboxylic acids is also demonstrated, providing the first method for
      the preparation of methyl and ethyl esters from aryl chlorides without pressured
      reactors.

PMID- 18720993
TI  - Azacalix[7]arene heptamethyl ether: preparation, nanochannel crystal structure,
      and selective adsorption of carbon dioxide.
AB  - To investigate the solid-state complexation of nitrogen-bridged calixarene
      analogues, azacalix[7]arene heptamethyl ether 1 has been prepared by applying a
      "5 + 2"-fragment coupling approach using Buchwald-Hartwig aryl amination reaction
      aided by our previously devised temporal N-silylation protocol. X-ray
      crystallographic analysis revealed that azacalix[7]arene 1 adopted a highly
      distorted 1,2-alternate conformation in the solid state as a result of
      intramolecular NH/O hydrogen bonding interactions and steric repulsion between
      the methoxy groups. In the crystal, molecules of 1 are mutually interacted by
      intermolecular NH/O and CH/pi interactions to establish one-dimensional (1D)
      hexane-filled nanochannel crystal architecture. Similarly to our recently
      reported azacalix[6]arene 2, the desolvated crystalline powder material of 1 was
      capable of selectively and rapidly adsorbing CO2 among the four main components
      of the atmosphere. The adsorption capacity of 1 for CO2 nearly doubled as
      compared to that of 2 because of the formation of the 1D nanochannel with almost
      twice the volume of the latter.

PMID- 18720994
TI  - [2.2]Paracyclophane-derived chiral P,N-ligands: design, synthesis, and
      application in palladium-catalyzed asymmetric allylic alkylation.
AB  - With the idea of tuning structural flexibility and rigidity, several
      [2.2]paracyclophane-derived P,N-ligands were designed and synthesized. A full
      investigation of the relationship between the ligands' structures and their
      abilities to induce asymmetry in palladium-catalyzed asymmetric allylic
      alkylations of malonates with 1,3-diphenyl 2-propenyl acetate was carried out,
      and high yields and enantioselectivities (i.e., 99% yield, 97% ee) were observed
      while using ligands bearing matched planar and central chirality.

PMID- 18720995
TI  - Surveying sterically demanding N-heterocyclic carbene ligands with restricted
      flexibility for palladium-catalyzed cross-coupling reactions.
AB  - Heterocyclic carbenes (NHCs), especially monodentate ones, have become the ligand
      of choice for many transition-metal-catalyzed transformations. They generally
      form highly stable complexes, have strong sigma-donor character, and have a
      unique shape that can be used to generate sterically demanding ligands.In this
      Account, we survey recent developments in the design and synthesis of some
      sterically demanding NHCs with a particularly strong influence on the metal's
      coordination sphere. We show the successful and insightful application of these
      ligands in transition-metal catalysis. First, we discuss methods for determining
      and classifying the electronic and steric properties of NHCs. In addition, we
      present data on the most important NHC ligands.The selective variation of either
      electronic or steric parameters of NHCs, and therefore of the catalyst, allows
      for the optimization of the reaction. Thus, we prepared several series of
      differentially substituted NHC derivatives. However, because the substituents
      varied were not directly connected to the carbene carbon, it was difficult to
      induce a large electronic variation. In contrast, an independent variation of the
      ligands' steric properties was more straightforward. We highlight three different
      classes of very sterically demanding NHCs that allow this kind of a steric
      variation: imidazo[1,5-a]pyridine-3-ylidenes, bioxazoline-derived carbenes
      (IBiox), and cyclic (alkyl)(amino)carbenes (CAAC).These latter NHC ligands can
      facilitate a number of challenging cross-coupling reactions. Successful
      transformations often require a monoligated palladium complex as the
      catalytically active species, and the sterically demanding NHC ligand favors this
      monoligated complex. In addition, the electron-rich NHC facilitates difficult
      oxidative addition steps. Moreover, the conformational flexibility of the ligands
      can facilitate the formation of catalytically active species and hemilabile
      interactions, such as agostic or anagostic bonds, as well as stabilize
      coordinatively unsaturated catalyst species. The increasing level of
      understanding of the role of NHC ligands in transition-metal catalysis will soon
      allow the design of even more sophisticated ligand systems.

PMID- 18720996
TI  - Effect of capillary pressure and surface tension on the deformation of elastic
      surfaces by sessile liquid microdrops: an experimental investigation.
AB  - Sessile liquid drops are predicted to deform an elastic surface onto which they
      are placed because of the combined action of the liquid surface tension at the
      periphery of the drop and the capillary pressure inside the drop. Here, we show
      for the first time the in situ experimental confirmation of the effect of
      capillary pressure on this deformation. We demonstrate micrometer-scale
      deformations made possible by using a low Young's modulus material as an elastic
      surface. The experimental profiles of the deformed surfaces fit well the
      theoretical predictions for surfaces with a Young's modulus between 25 and 340
      kPa.

PMID- 18720997
TI  - Electrowetting-based microdrop tensiometer.
AB  - We performed electrowetting (EW) contact angle measurements to determine the
      interfacial tension between aqueous drops laden with various inorganic and
      organic solutes and various ambient oils. Using low frequency AC voltage, we
      obtained interfacial tensions from 5 to 72 mJ/m 2, in close agreement with
      macroscopic tensiometry for drop volumes between 20 and 2000 nL. In addition to
      the conventional EW geometry, we demonstrate the possibility of performing
      "contact-less" measurements without any loss of accuracy using interdigitated
      coplanar electrodes.

PMID- 18720998
TI  - Polymer/silica nanocomposites: preparation, characterization, properties, and
      applications.

PMID- 18720999
TI  - Investigating pharmacology in vivo using magnetic resonance and optical imaging.
AB  - The better and earlier a disease can be diagnosed and characterized, the greater
      the chance of being able to intervene in this process with a chemical entity.
      This is the rationale for the use of in vivo imaging techniques in the drug
      discovery and development process. In this article we address the value of two
      imaging modalities in this area, i.e. magnetic resonance imaging (MRI) and
      optical imaging. The multiparametric nature of MRI enables anatomical,
      functional, metabolic and, to a certain extent, also cellular and target-related
      information to be obtained noninvasively at high spatial resolution. This favours
      characterization of a disease state and the corresponding drug intervention. The
      noninvasiveness of MRI strengthens the link between preclinical and clinical
      pharmaceutical research. The high sensitivity of optical techniques enables
      molecular information to be obtained in vivo. Within pharmacological research,
      the main applications of optical techniques relate to the early drug discovery
      process and acquisition of target-related information. However, potential
      clinical applications of optical imaging are also emerging. The complementary
      character of both imaging modalities renders them useful in various portions of
      the drug discovery process, from early target selection and validation to
      clinical studies.

PMID- 18721000
TI  - Applications of metabolomics in drug discovery and development.
AB  - Metabolomics is a relatively new field of 'omics' technology that is primarily
      concerned with the global or system-wide characterization of small molecule
      metabolites using technologies such as nuclear magnetic resonance, liquid
      chromatography and/or mass spectrometry. Its unique focus on small molecules and
      the physiological effects of small molecules aligns the field of metabolomics
      very closely with the aims and interests of many researchers in the
      pharmaceutical industry. Because of its conceptual and technical overlap with
      many aspects of pharmaceutical research, metabolomics is now finding applications
      that span almost the full length of the drug discovery and development pipeline,
      from lead compound discovery to post-approval drug surveillance. This review
      explores some of the most interesting or significant applications of metabolomics
      as they relate to pharmaceutical research and development. Specific examples are
      given that show how metabolomics can be used to facilitate lead compound
      discovery, to improve biomarker identification (for monitoring disease status and
      drug efficacy) and to monitor drug metabolism and toxicity. Other applications
      are also discussed, including the use of metabolomics to facilitate clinical
      trial testing and to improve post-approval drug monitoring. These examples show
      that metabolomics potentially offer drug researchers and drug regulators an
      effective, inexpensive route to addressing many of the riskier or more expensive
      issues associated with the discovery, development and monitoring of drug
      products.

PMID- 18721001
TI  - Role of neuroimaging in analgesic drug development.
AB  - Rapidly developing, non-invasive, neuroimaging methods provide increasingly
      detailed structural and functional information about the nervous system, helping
      advance our understanding of pain processing, chronic pain conditions and the
      mechanisms of analgesia. However, effective treatment for many chronic pain
      conditions remains a large, unmet medical need. Neuroimaging techniques may
      enhance our understanding of why currently available analgesics are ineffective
      for so many patients and aid in identifying new neural targets for
      pharmacological interventions of pain. This review examines how neuroimaging has
      enhanced our understanding of the mechanisms of chronic pain, the neural
      correlates of pharmacological modulation of pain, and the role of neuroimaging in
      analgesic development. Rather than focusing on one method, we discuss the
      advantages and limitations of several techniques that may each serve a unique
      role in aiding drug development, and we discuss current issues that exist in the
      design and implementation of pharmacological neuroimaging studies. Particularly,
      experimental design must be carefully considered as there are limitations in
      terms of the pharmacokinetics of the drug of interest as well as in respect to
      the capabilities of the neuroimaging method in use. Finally, we identify future
      directions including novel approaches that may also play a role in furthering our
      knowledge of the neural basis of analgesia. In the future, neuroimaging will
      certainly impact the methodology of analgesic drug development as it may lead to
      quicker and more efficient methods of evaluating the neural modulation of chronic
      pain.

PMID- 18721002
TI  - Cinacalcet does not affect the activity of cytochrome P450 3A enzymes, a
      metabolic pathway for common immunosuppressive agents : a randomized, open-label,
      crossover, single-centre study in healthy volunteers.
AB  - BACKGROUND AND OBJECTIVE: Cinacalcet HCl (cinacalcet) is approved for the
      treatment of secondary hyperparathyroidism in subjects receiving dialysis and for
      the reduction of hypercalcaemia in patients with parathyroid carcinoma. The drug
      may also be co-administered with medications used in the renal transplantation
      setting, such as immunosuppressants. Cinacalcet, as well as some
      immunosuppressants such as ciclosporin, tacrolimus and sirolimus, is partially
      metabolized by the cytochrome P450 3A enzymes (CYP3A). This study aimed to
      evaluate the potential inhibitory effects of cinacalcet on CYP3A activity using
      midazolam as a probe substrate in healthy volunteers. METHODS: In this
      randomized, open-label, crossover, two-treatment, two-period, single-centre
      study, 12 healthy volunteers received either oral cinacalcet 90 mg once daily for
      5 days plus a single oral dose of midazolam 2 mg on day 5, or a single oral dose
      of midazolam 2 mg on day 1. Following a 10-day washout period, subjects received
      the alternate treatment. Blood samples were collected predose and at selected
      time points up to 24 hours after dosing with midazolam for measurement of
      midazolam pharmacokinetic parameters. RESULTS: Eleven subjects completed the
      study. Mean (standard deviation) midazolam maximum plasma concentrations (C(max))
      and area under the plasma concentration-time curve from time zero to infinity
      (AUC(infinity)) were 9.31 (3.09) ng/mL and 24.1 (7.7) ng . h/mL, respectively,
      when administered in combination with cinacalcet, compared with 9.76 (2.81) ng/mL
      and 22.8 (6.1) ng . h/mL when administered alone. The mean geometric ratios (90%
      confidence interval) were 0.95 (0.84, 1.06) and 1.05 (0.95, 1.16) for C(max) and
      AUC(infinity), respectively. All adverse events were mild to moderate in
      severity, and consistent with the safety profile of cinacalcet. CONCLUSION: Once
      daily administration of cinacalcet did not alter the pharmacokinetics of
      midazolam relative to administration of midazolam alone. These data suggest that
      cinacalcet administration does not affect CYP3A activity, and thus would not have
      an effect on any drug eliminated via CYP3A, including some commonly used
      immunosuppressant therapies.

PMID- 18721003
TI  - No relationship between plasma desacyl-ghrelin levels and rabeprazole-related
      delay in gastric emptying : controlled study in healthy volunteers.
AB  - BACKGROUND AND OBJECTIVE: Recent studies have indicated that rabeprazole, a
      proton pump inhibitor, delays gastric emptying. However, the mechanism of action
      remains unclear. We conducted this study to clarify whether desacyl-ghrelin (the
      inactive form of the endogenous growth hormone secretagogue receptor ghrelin) is
      involved in rabeprazole-induced changes in gastric motor function. METHODS:
      Twelve healthy males underwent (13)C-acetate breath tests to evaluate gastric
      emptying of a liquid meal twice after administration of rabeprazole 20 mg/day for
      3 days or no medication (control). Gastric emptying was evaluated by two
      parameters: half-emptying time and time to peak (13)CO(2) excretion. Plasma
      desacyl-ghrelin levels were measured in blood samples collected at three time
      points: immediately pre-test and 1 and 2 hours after ingestion of the test meal.
      RESULTS: Rabeprazole significantly delayed gastric emptying of the liquid meal.
      However, plasma desacyl-ghrelin levels after ingestion of the liquid meal showed
      little difference before or after rabeprazole administration. CONCLUSION: The
      results indicate that desacyl-ghrelin was not associated with changes in gastric
      emptying caused by rabeprazole.

PMID- 18721004
TI  - Cardiac findings in fetal and pediatric autopsies: a five-year retrospective
      review.
AB  - This review aims to determine the spectrum of cardiac findings in our fetal and
      pediatric postmortem population and provide an analysis of associated
      extracardiac malformations and genetic abnormalities. Pediatric autopsy reports
      from 2003 to 2007 inclusive were reviewed and cases with cardiac pathology
      selected for analysis. Over the 5-year period, 119 cases (10.8%) with abnormal
      cardiac findings were identified from a total of 1102 postmortem examinations. Of
      these cardiac cases, 42% were after termination of pregnancy for fetal anomaly,
      29% after fetal demise, 14% after neonatal unit death, 3% after hospital
      inpatient death, and 11% after sudden unexpected death. Structural abnormality
      cases numbered 107 (90%), with ventricular septal defect as the most common
      individual defect. Nonstructural abnormality cases, such as myocarditis, numbered
      12 (10%). Extracardiac malformations were identified in 78%. Chromosome or gene
      aberrations were detected in 37%. This review highlights the potential benefit of
      introducing routine fetal anomaly scanning, the need for cardiac pathology
      training for pediatric pathologists, and the importance of examination of the
      heart and associated vessels in all cases to provide parents with as much
      information as possible and aid identification of the etiology and associations
      of cardiac pathology.

PMID- 18721005
TI  - Juvenile myelomonocytic leukemia: report of seven cases and review of literature.
AB  - Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive, clonal
      hematopoietic disorder of childhood with features of both myelodysplasia
      (thrombocytopenia, anemia) and myeloproliferation (leukocytosis, monocytosis). In
      most cases there is marrow hypercellularity, splenomegaly, and extramedullary
      involvement. In 1997 an international consensus on terminology was reached and
      guidelines/criteria for diagnosis were proposed. A recent World Health
      Organization classification described the current diagnostic criteria of JMML.
      Although the diagnosis of JMML has been facilitated, it can be challenging,
      especially in the early stages or when it 1st presents as an extramedullary
      tumor. We report a series of 7 cases diagnosed over a period of 10 years (from
      January 1, 1996, to December 31, 2005). Two cases had interesting associated
      findings that would potentially lead to delay in diagnosis or misdiagnosis. Two
      other cases had extramedullary involvement with symptoms referable to the organs
      of involvement at presentation. Clinical and pathologic findings are summarized
      with a review of relevant literature.

PMID- 18721006
TI  - Comparing quality-of-life outcomes in symptomatic patients undergoing
      laparoscopic or open ventral hernia repair.
AB  - BACKGROUND: The aim of this study was to compare quality-of-life outcomes in
      patients with symptomatic hernias who were undergoing laparoscopic and open
      repairs. MATERIALS AND METHODS: Clinical data for patients undergoing ventral
      hernia repair were reviewed with quality-of-life surveys administered before and
      at least 6 months following surgery. RESULTS: The study included 56 symptomatic
      patients. Forty-one patients (73%) underwent laparoscopic repair, and 15 patients
      (27%) underwent open repair. There was no difference in preoperative quality-of
      life scores on the SF-36 Health Survey between patients having laparoscopic or
      open repairs. Postoperative quality-of-life scores on the SF-36 survey were
      significantly improved in the laparoscopic group, compared with the open group,
      in general health (46% vs. 37%; P=0.0217), vitality (53% vs. 45%; P=0.0491), role
      emotional (45% vs. 35%; P=0.0480), and mental health (49% vs. 39%; P=0.0381).
      Postoperative quality-of-life scores on the Carolinas Comfort Scale (CCS) were
      significantly improved in the laparoscopic group, compared with the open group,
      in bending over (3.15 vs. 5.87, P=0.0158), sitting up (2.51 vs. 5.13; P=0.0211),
      activities of daily living (2.48 vs. 5.75; P=0.0139), coughing or deep breathing
      (2.95 vs. 5.75; P=0.0314), walking (2.36 vs. 4.62; P=0.0427), exercising (3.19
      vs. 6.14; P=0.0222), and total comfort scale (17.62 vs. 40.23; P=0.0084).
      CONCLUSIONS: Laparoscopic ventral hernia repair provides improved quality-of
      life, compared with open repair, 6 months postoperatively. Nearly all physical
      variables measured by the CCS were significantly better when ventral hernias were
      repaired laparoscopically.

PMID- 18721007
TI  - LATG with extracorporeal esophagojejunostomy: is this minimal invasive surgery
      for gastric cancer?
AB  - BACKGROUND: This retrospective study determined whether extracorporeal
      esophagojejunostomy after laparoscopy-assisted total gastrectomy (LATG) for
      gastric cancer can be considered minimally invasive surgery, compared to the
      conventional open total gastrectomy (OTG). PATIENTS AND METHODS: This
      retrospective study involved 60 patients seen between January 2004 and July 2006.
      Twenty-seven patients underwent LATG, and 33 patients had OTG. The surgical
      procedure included the use of five ports with an upper vertical midline incision.
      In all patients, reconstruction was performed by using a Roux-en-Y
      esophagojejunostomy through the minilaparotomy site. In all cases, the
      jejunojejunostomy was performed extracorporeally as the conventional method. In
      OTG, a Roux-en-Y esophagojejunostomy was performed with an upper midline
      incision. RESULTS: The mean number of retrieved lymph nodes was smaller and the
      mean operating time was longer in the LATG group. The postoperative hospital
      course was similar in both groups. In the LATG group, the mean length of the
      minilaparotomy incision was 8.0+/-1.2 cm (maximum length, 11 cm), and a direct
      relationship was observed between the distance from the xiphoid process to the
      esophageal hiatus (DisXE) and the minilaparotomy incision length (Spearman's
      correlation of rank coefficient: 0.386; P=0.046). CONCLUSIONS: With the concept
      of minimal invasiveness, if the patient's DisXE exceeds 9 cm, the length of the
      minilaparotomy incision in laparoscopic surgery could be disadvantageous.
      Nevertheless, we consider LATG the treatment of choice for early gastric cancer.
      If the patient's DisXE exceeds 9 cm, we consider intracorporeal anastomosis with
      the laparoscopic total gastrectomy. The type of esophagojejunostomy may be
      determined preoperatively by using three-dimensional abdominal computed
      tomography.

PMID- 18721008
TI  - Transumbilical endoscopic appendectomy in humans: on the road to NOTES: a
      prospective study.
AB  - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) is the newest
      technique emerging in the field of surgery. There are several techniques
      described in the literature, though there is no standardization yet. In this
      paper, we describe a transumbilical approach for the endoscopic appendectomy in
      humans. MATERIALS AND METHODS: Eight of 12 patients with uncomplicated
      appendicitis successfully underwent a transumbilical endoscopic appendectomy.
      Patients with a mass, abscessed or perforated appendix, previous lower abdominal
      surgeries, and conversion to laparoscopy (4 patients) were excluded. RESULTS: The
      average age of the patients was 32.5 years. The mean operating time was 95
      minutes, and the conversion rate was 33.3%. Only 1 dose of intravenous analgesics
      was administered postoperatively. Hospital stay was 1-3 days. The follow-ups were
      scheduled at 7, 30, and 90 days and 8 months. Six patients completed all the
      follow-ups and experienced no problems. DISCUSSION: So far, this transumbilical
      approach to the appendectomy in humans has not been reported. We think that this
      method of approach is an effective technique by itself and an ideal "stepping
      stone" to NOTES, as well as helpful to train laparoscopic surgeons to make the
      transition to full-fledged NOTES. Unlike the transgastric or transvaginal
      approaches, the umbilical approach allows an easy maneuverability of the
      endoscope, though at the cost of an umbilical scar. The technical ease of the
      procedure and early outcome seem satisfactory. This technique may be considered
      as a "precursor" to NOTES.

PMID- 18721009
TI  - NOTES: a review of the technical problems encountered and their solutions.
AB  - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) is currently
      investigated and developed worldwide. In the past few years, multiple groups have
      confronted this challenge. Many technical problems are encountered in this
      technique due to the currently available tools for this approach. Some of the
      unique technical problems in NOTES include: blindly performed primary incisions;
      uncontrolled pneumoperitoneal pressure; no support for the endoscope in the
      abdominal cavity; inadequate vision; insufficient illumination; limited
      retraction and exposure; and the complexity of suturing and performing a safe
      anastomosis. In this paper, we review the problems encountered in NOTES and
      provide possible temporary solutions. METHODS: Acute and survival studies were
      performed on 15 farm pigs. The hybrid technique approach (i.e., endoscopic
      surgery with the aid of laparoscopic vision) was performed in all cases.
      Procedures performed included liver biopsies, bilateral tubal ligation,
      oophprectomy, cholecystectomy, splenectomy and small bowel resection, and
      anastomosis. RESULTS: All attempted procedures were successfully performed. New
      methods and techniques were developed to overcome the technical problems. Closure
      of the gastrotomy was achieved by T-bar sutures and by stapler closure of the
      stomach incision. Small bowel anastomosis was achieved by the dual-lumen NOTES
      technique. CONCLUSIONS: The hybrid technique serves as a temporary approach to
      aid in developing the NOTES technique. A rectal or vaginal port of entry enables
      and facilitates gastrointestinal NOTES by using available laparoscopic
      instruments. The common operations performed today in the laparoscopic fashion
      could be probably performed in the NOTES approach. The safety of these
      procedures, however, is yet to be determined.

PMID- 18721010
TI  - Laparoscopic bilateral simultaneous adrenalectomy: results of 11 operations.
AB  - BACKGROUND: This study was undertaken to evaluate the outcomes of the
      simultaneous bilateral laparoscopic adrenalectomy. MATERIALS AND METHODS: This
      was a retrospective study, including 11 patients with bilateral adrenal lesions,
      affected by Cushing's syndrome (n=2), Cushing's disease (n=6), pheochromocytoma
      (n=2), and 1 adrenocorticotrophin-hormone-dependent hypercortisolism of unknown
      origin. RESULTS: Elevan bilateral adrenalectomies were carried out by the
      laparoscopic approach with no conversions. The operations were performed in 7
      cases by the lateral transperitoneal adrenalectomy (LTLA), in 3 by the posterior
      approach (PRA), and in 1 by the combined approach. The mean size of the masses
      was 5 cm. (range, 4-13). The average operating time was 245 minutes for LTLA and
      218 minutes for PRA (P<0.05). The estimated mean blood loss was 87+/-36 mL
      (range, 20-150). No patients required transfusions. The mean hospital stay was
      5+/-1.8 days (range, 4-7). The mean follow-up was 34 months (range, 2-96).
      CONCLUSIONS: Our study confirms that the bilateral adrenalectomy by the minimally
      invasive technique is safe and effective, affording acceptable blood loss and
      morbidity with a short hospital stay.

PMID- 18721011
TI  - Clipless laparoscopic cholecystectomy by ultrasonic dissection.
AB  - BACKGROUND: Ultrasonically activated devices have been used in gallbladder
      dissection in the laparoscopic cholecystectomy with encouraging results. The aim
      of this study was to compare between the safety and efficacy of the harmonic
      shears and the commonly used clip and cautery technique in achieving safe closure
      and division of the cystic duct in the laparoscopic cholecystectomy. METHODS: In
      this prospective study, 120 patients with symptomatic gallstone disease were
      randomly assigned to either the harmonic scalpel laparoscopic cholecystectomy
      group (HS group=60 patients) where closure and division of the cystic duct was
      achieved solely by the harmonic shears or the clip and cautery laparoscopic
      cholecystectomy group (C&C group=60 patients). RESULTS: Neither minor nor major
      bile leaks were encountered in either group. Similarly, no bile-duct injuries
      were encountered in the present study. The incidence of gallbladder perforation
      was statistically significantly higher in the C&C group, compared to the HS group
      (30 vs. 10%, respectively; P=0.002). The median operative time was statistically
      significantly shorter in the HS group than in the C&C group (32 vs. 40 minutes,
      respectively; P=0.000). No statistically significant difference was found in the
      incidence of postoperative complications between both groups. CONCLUSIONS: The
      harmonic shears are as safe and effective as the commonly used clip and cautery
      technique in achieving safe closure and division of the cystic duct in the
      laparoscopic cholecystectomy. Further, it provides a superior alternative to the
      currently used high-frequency monopolar technology in terms of shorter operative
      time and lower incidence of gallbladder perforation.

PMID- 18721012
TI  - Emergency laparoscopy for acute abdominal conditions: a prospective study.
AB  - BACKGROUND: Currently, emergency laparoscopic surgery for acute abdominal
      conditions has become the favored surgical approach; therefore, we investigated
      the diagnostic accuracy and therapeutic efficacy of laparoscopy in acute
      abdominal pain in Saudi Arabian patients. PATIENTS AND METHODS: In this
      prospective study, 176 patients with acute abdominal pain (113 patients with pain
      localized to the right iliac region [group A] and 63 patients with generalized
      abdominal pain [group B] underwent emergency laparoscopy between January 2002 and
      December 2006. We evaluated the initial clinical diagnosis, the laparoscopic
      diagnosis, and the outcome in these two groups of patients. RESULTS: In group A,
      a definitive diagnosis was established at laparoscopy in 89% of patients, and it
      was therapeutic in 81.4% of the patients, and in 9 patients (8%) a conversion to
      laparotomy was necessary a to manage their condition. In group B, the diagnosis
      was accurate in 87% of patients, and it was therapeutic in 79.4% of the patients,
      and in 5 patients (8%) a conversion to laparotomy was necessary. There was no
      mortality. CONCLUSIONS: The emergency laparoscopy is a diagnostic and therapeutic
      option in the majority of acute abdominal pain conditions.

PMID- 18721013
TI  - Laparoscopic treatment of a huge cystic lymphangioma: partial aspiration
      technique with a spinal needle.
AB  - A cystic lymphangioma is a rare intra-abdominal lesion. Treatment is a complete
      excision of the cyst because of complications and a rare chance of malignancy. In
      this paper we report on 2 patients with a huge cystic lymphangioma who were
      treated by laparoscopic surgery successfully. Each of the cysts were 13 and 11 cm
      in diameter, were diagnosed by ultrasonography and computed tomography scan.
      After partial aspiration of the cysts, using a spinal needle, we were prone to
      grasp the cysts without spillage. Traction and dissection were easy without
      spillage or injury of the mesenteric vessels. The laparoscopic approach can be
      successfully and safely performed by an experienced surgeon in keeping with
      oncologic principles.

PMID- 18721014
TI  - Extraluminal appendicolith: an indication for interval appendectomy with
      intraoperative localization and removal of that potential cause of intra
      abdominal abscess.
AB  - Appendicoliths are formed by calcium salts and fecal debris layered and lodged
      within the appendix. They are detected on unenhanced X-rays in <10% of patients
      with appendicitis. When an appendicolith is found extraluminally, it is
      pathognomonic for perforation of the appendix. Moreover, retained appendicoliths
      are likely to be infected and to be the source of a postoperative intraperitoneal
      abscess, whereupon the only definitive treatment is surgical excision. In this
      paper, we describe an asymptomatic patient with evidence of an extraluminal
      appendicolith on computed tomography following successful conservative treatment
      for a periappendicular abscess. She underwent a laparoscopic interval
      appendectomy that included the removal of an extraluminal appendicolith and was
      released home on the following day. We advocate this approach in order to prevent
      the possible formation of an intra-abdominal abscess caused by an infected nidus.

PMID- 18721015
TI  - Laparoscopic removal of a perforating intrauterine device mimicking chronic
      appendicitis.
AB  - The intrauterine contraceptive device (IUD) is a common form of reversible birth
      control. One of the rare, but serious, complications is uterine perforation. In
      this paper, we report a case of a patient who underwent laparoscopy for presumed
      chronic appendicitis. Intraoperatively, uterine perforation by the IUD was found.
      The IUD was removed laparoscopically. The postoperative course was uneventful.

PMID- 18721016
TI  - Laparoscopic partial splenectomy using radiofrequency ablation.
AB  - INTRODUCTION: Epidermoid cysts are believed to be congenital in origin and often
      present in the pediatric population. Because of the concerns of compromised
      immunologic function after total splenectomy and increasing demand for minimally
      invasive approaches, interest has increased in performing the partial splenectomy
      in this patient population by laparoscopic techniques. Nonetheless, concerns for
      adequate hemostasis have limited its widespread adoption. Because radiofrequency
      ablation for the partial splenectomy has been done in a laparoscopic porcine
      model with good results, we used this technology with the goal of limiting blood
      loss and postoperative hemorrhagic complications. CASE REPORT: A 25-year-old
      female presented with complaints of right shoulder pain. Abdominal ultrasound and
      a computed tomography (CT) scan revealed a 10-cm cystic lesion of the spleen.
      Serology was negative for hydatid cyst pathology. The patient underwent an
      uneventful partial splenectomy by minimally invasive techniques with the aid of a
      laparoscopic radiofrequency ablative device and the placement of a hemostatic
      medicated sponge along the line of transection. RESULTS: Estimated blood loss was
      less than 30 mL. Final pathology was consistent with an epidermoid splenic cyst,
      and the patient was discharged uneventfully on postoperative day 5. DISCUSSION:
      Techniques for the treatment of symptomatic splenic cysts range from total
      splenectomy to cyst fenestration and placement of the omentum in the splenic
      defect. The use of radiofrequency ablation has been traditionally used for
      hepatic parenchymal transection but seems equally suited for the partial
      splenectomy. This technology, and the addition of hemostatic sponges, seems to
      provide excellent results in minimizing blood loss, intraoperatively and
      postoperatively, during the laparoscopic partial splenectomy; however,
      randomized, prospective trials will be necessary to see if they will be superior
      to traditional techniques.

PMID- 18721017
TI  - Laparoscopic ligation of the thoracic duct for the treatment of traumatic
      chylothorax.
AB  - Laparoscopic ligation of the thoracic duct was successfully used in the treatment
      of traumatic chylothorax where video-assisted thoracoscopy and conservative
      methods had failed. This minimally invasive approach contributed to the early
      discharge of our patient.

PMID- 18721019
TI  - A new technique for intracorporeal knot tying in laparoscopic surgery.
AB  - INTRODUCTION: Laparoscopic intracorporeal knot tying in minimally invasive
      surgery is an advanced skill. Mastering this skill is a difficult process with a
      long learning curve. Intracorporeal suturing is essential to advanced laparoscopy
      and is a rate-limiting step in many procedures. Many different instruments and
      methods have been described for laparoscopic suturing and knot tying. We have
      developed a new technique for laparoscopic knot tying. TECHNIQUE: The long end of
      the suture is held with a left-hand instrument, and the instrument is rotated for
      360 degrees in a clockwise direction to make a forward-direction loop. The end of
      the loop is grasped with the right-hand instrument, and the other end of the
      suture is grasped with the left-hand instrument. The suture end, held by the left
      hand, is pulled though the loop and tied, thus making a half-knot of a square
      knot. The second half-knot is made by using the right-hand instrument with the
      same technique. DISCUSSION: Laparoscopic suturing and knotting is difficult to
      perform, especially when the angle between the working instruments is narrow and
      working space is limited. In all these situations, knot tying using this
      technique makes knotting more simple and easy to perform, especially for those
      who have limited experience in intracorporeal suturing and knot tying. No special
      instrument is required to perform knot tying with this technique.

PMID- 18721018
TI  - Evaluation of unmeshed and 1:1 meshed AlloDerm bolsters for stapled rectal
      anastomoses in a porcine model.
AB  - INTRODUCTION: The major morbidity of colorectal anastomoses is leaks. The concept
      of staple-line reinforcement is a growing area of interest. In this study, we
      evaluated the feasibility and effect of utilizing AlloDerm to bolster end-to-end
      stapled rectal anastomoses in a porcine model. METHODS: A total of 30 female 45
      kg domestic pigs were studied, and each served as its own control by creating a
      bolstered and unbolstered anastomosis in each animal. All anastomoses were
      created with a 29-mm end-to-end stapling device. Bolstered anastomoses were
      randomized to proximal and distal positions along the rectum, and each
      rectorectal anastomosis was separated by an average of 10 cm. In 20 pigs, an
      unmeshed bolster of a 0.5-0.7-mm thickness was used. The remaining 10 pigs had a
      1:1 meshed bolster that was 0.34-0.51 mm thick. The animals were survived for 14
      days. Barium enemas were then performed and the two anastomotic sites harvested,
      and each anastomosis underwent burst testing. The internal diameter of each
      anastomosis was measured and a biochemical analysis was performed for matrix
      metalloproteinase (MMP), elastin and collagen content. RESULTS: The unmeshed
      bolstered anastomoses burst fewer times than the unbolstered anastomoses
      (P=0.004) and had higher burst pressures (P=0.023), though their anastomotic
      circumferences were smaller (P=0.007). Meshed bolsters offered no strength
      advantage to anastomoses and were significantly (P=0.009) smaller than
      unbolstered anastomoses in the same animal. No difference in elastin, collagen,
      or MMP content was observed between bolstered and unbolstered groups. No animals
      had clinical or radiographic leaks. CONCLUSIONS: The routine use of unmeshed and
      1:1 meshed AlloDerm bolsters is safe and does not appear to inhibit healing in
      elective colorectal surgery on healthy subjects. AlloDerm may have a role as a
      tissue bolster in select patients who are more prone to develop anastomotic
      leaks.

PMID- 18721020
TI  - Laparoscopic repair of paraesophageal hiatal hernias.
AB  - The advent of minimally invasive techniques has brought about a shift in the
      operative approach of patients with paraesophageal hiatal hernia. Today, the
      laparoscopic repair of a paraesophageal hiatal hernia has almost completely
      replaced the open approach through either a laparotomy or a left thoracotomy. The
      laparoscopic repair of paraesophageal hiatal hernias is a technically challenging
      operation; however, it is technically feasible and safe, and it is associated
      with a positive relief of symptoms, decreased postoperative pain, and a rapid
      return to normal activities (1, 2). This paper describes, step by step, our
      approach to the laparoscopic repair of a paraesophageal hiatal hernia.

PMID- 18721021
TI  - Removal of 1300-g uterus by laparoscopic hysterectomy with retroperitoneal
      uterine artery sealing using LigaSure.

PMID- 18721022
TI  - Evolution of the surgical management of neonatal ovarian cysts: laparoscopic
      assisted transumbilical extracorporeal ovarian cystectomy (LATEC).
AB  - PURPOSE: Since its first detailed description in 1995, the laparoscopic
      management of neonatal ovarian cysts has typically required multiple incisions,
      specialized equipment, and advanced laparoscopic skills. After some initial
      frustration with neonatal laparoscopy, we developed a simplified single-incision
      laparoscopic-assisted transumbilical extracorporeal cystectomy (LATEC). This
      paper reviews our experience with this technique and compares outcomes to those
      of our other surgically managed neonatal ovarian cyst patients. MATERIALS AND
      METHODS: A retrospective record review of 20 patients treated surgically between
      1992 and 2006. Student's t-tests were used for comparisons (P<0.05 was
      significant). RESULTS: Means were: age, 11 days; weight, 3.7 kg; and cyst
      diameter, 5.0 cm. Nineteen patients were diagnosed prenatally, at the mean
      gestational age of 33 weeks. Twelve of 20 (60%) had torsed cysts (1 bilateral).
      Three of 13 torsed cysts (23%) were less than 4 cm diameter (range, 2.9-3.5).
      Laparotomies were transverse lower abdominal incisions. Laparoscopic operations
      used 2 (3 patients) or 3 incisions (2 patients). LATEC involved transumbilical
      laparoscopy, complete cyst aspiration, and then cyst evisceration through the
      umbilicus for either ovarian cystectomy (simple cysts) or salpingo-oophorectomy
      (torsed cysts). Laparoscopic patients had similar time to feeds, length of stay,
      and postoperative narcotic requirements, when compared to laparotomy patients
      (P=nonsignificant). LATEC patients had shorter surgical times, more rapid
      advancement to full enteral feedings, shorter length of hospital stay, and equal
      ovarian preservation, when compared to laparoscopy. Cosmetic results with LATEC
      were outstanding. CONCLUSIONS: Both laparoscopic and "open" approaches have
      acceptable perioperative morbidity and rapid recovery. LATEC is a relatively
      simple procedure, which combines laparoscopy and traditional extracorporeal
      surgery, and may be successfully performed by experienced pediatric surgeons and
      with a single incision.

PMID- 18721023
TI  - Laparoscopic treatment of simultaneously occurring pyloric stenosis and
      malrotation.
AB  - Hypertrophic pyloric stenosis (HPS) is a common cause of nonbilious vomiting in
      the neonatal period with an incidence of approximately 1 to 3 per 1000 live
      births. The Ramstedt pyloromyotomy has been the standard treatment since 1912. In
      1991, Alain et al. reported a novel approach to HPS using laparoscopy. Since this
      original description, the laparoscopic pyloromyotomy has become progressively
      more popular and, in many institutions, has replaced the open approach.
      Similarly, malrotation is a condition affecting the neonatal population,
      resulting from incomplete intestinal rotation about the superior mesenteric
      artery during weeks 10 through 11 of development. If left untreated, it can lead
      to abnormal mesenteric attachments and a narrowed mesenteric base, placing the
      patient at risk for midgut volvulus. The standard surgical treatment has been the
      open Ladd procedure first described in 1932. In 1996, Gross described a minimally
      invasive procedure to address malrotation. The association of concurrent pyloric
      stenosis and malrotation has rarely been reported in the pediatric literature.
      This is the first published report of a laparoscopic treatment of HPS and
      malrotation simultaneously.

PMID- 18721024
TI  - Laparoscopic drainage of postappendectomy- retained fecalith and intra-abdominal
      abscess in the pediatric population.
AB  - Retained fecalith after an appendectomy is an uncommon complication frequently
      associated with intra-abdominal abscess. Treatment options include percutaneous,
      open, or laparoscopic drainage of the abscess and retrieval of the fecalith, as
      antibiotics and drainage alone are usually insufficient. Laparoscopy offers the
      advantages of enhanced visualization of the abdomen, improved cosmesis, and a
      quicker return to normal daily activities. The principles of laparoscopic
      treatment include the careful identification of all anatomic landmarks, as the
      abscesses are frequently adherent to intra-abdominal structures compromising the
      safety of the operation. In this paper, we present 2 cases of laparoscopic
      drainage of an intra-abdominal abscess with retrieval of a fecalith in pediatric
      patients 1 and 6 weeks after an initial appendectomy and a review the literature.

PMID- 18721025
TI  - Laparoscopic finding of chylous ascites and intestinal malrotation in an infant
      presenting with left inguinal hernia.
AB  - This case report illustrates an unexpected advantage of using the laparoscopic
      approach for inguinal hernia repair in infants. In this paper, we report an
      infant referred to us with a diagnosis of an irreducible left inguinal hernia. He
      presented with a 1-day history of bilious vomiting and poor weight gain on
      breastfeeding. On arrival, a reducible left inguinal hernia was found and he was
      scheduled to have a laparoscopic inguinal hernia repair. During laparoscopy,
      chylous ascites was noted and the transverse colon and appendix could not be
      visualized. This raised the suspicion of malrotation with obstruction, which was
      confirmed on an upper gastrointestinal contrast study. He was taken back to the
      operating theater and a malrotation with volvulus was confirmed at laparotomy. A
      Ladd's procedure was performed, and he made an uneventful recovery.

PMID- 18721026
TI  - Laparoscopic duodenoduodenostomy in a newborn with situs inversus totalis.
AB  - Situs viscerum inversus is a rare embryologic anomaly with a mirror-image
      transposition of the normal anatomy of organs. The coexistence with the duodenal
      atresia is extremely rare. This report describes a newborn with duodenal atresia
      and situs inversus totalis who was managed laparoscopically. According to our
      knowledge, this is the first report of this type of associated anomaly to be
      successfully managed by the laparoscopic approach.

PMID- 18721027
TI  - Management of abdominal compartment syndrome in a very low birth weight neonate
      using Penrose drains and subsequent management of abdominal-wall defects.
AB  - Percutaneous drainage of the peritoneal cavity has been recently evaluated for
      the treatment of perforated viscous in the very low birth weight (VLBW) neonate
      and percutaneous decompression for abdominal compartment syndrome (ACS) has been
      studied in older patient populations. This is the first reported case of using
      this technique to treat ACS in a VLBW neonate.

PMID- 18721028
TI  - Thoracoscopic repair for right congenital diaphragmatic hernia.
AB  - PURPOSE: The aim of this study is to describe the surgical technique and initial
      results of thoracoscopic repair for the right congenital diaphragmatic hernia
      (CDH). METHODS: Patients underwent surgery under conventional general anesthesia.
      The operation was carried out by using one optical and two operating trocars.
      Pleural insufflation with carbon dioxide was maintained at a pressure of 2-4 mm
      Hg. The hernia defect was repaired by using nonabsorbable interrupted sutures
      with extracorporeal knots. RESULTS: There were 16 patients, including 13 boys and
      3 girls. Six patients were newborns and the other 10 patients were infants or
      elders. The mean operative time was 82 minutes. Conversion was required in 1
      patient. There were no operative or postoperative complications. However, there
      was one postoperative death. There was one recurrence on postoperative day 39.
      Follow-up ranged from 2 to 77 months. A normal chest X-ray was shown in all
      patients. CONCLUSION: Thoracoscopic repair is feasible and safe for children with
      a right CDH, including selected newborns.

PMID- 18721032
TI  - The accident of gender.

PMID- 18721033
TI  - The senses grow skilled in their craving: thoughts on creativity and addiction.

PMID- 18721034
TI  - The language of the unconscious: poetry and psychoanalysis.

PMID- 18721035
TI  - In the light of mourning: spiritual transformations between trauma and presence.

PMID- 18721036
TI  - I was looking for a different treatment.

PMID- 18721039
TI  - Robotic nephrectomy for kidney cancer in a horseshoe kidney with renal vein tumor
      thrombus: novel technique for thrombectomy.

PMID- 18721040
TI  - Anomalous renal vasculature: a laparoscopic perspective.

PMID- 18721041
TI  - Technological advances in transurethral resection of the prostate: bipolar versus
      monopolar TURP.
AB  - One of the most significant recent advancements in transurethral resection of the
      prostate (TURP) is the incorporation of bipolar technology. Bipolar circuitry
      allows TURP to be performed in a normal saline environment, which addresses a
      fundamental concern of conventional monopolar TURP (i.e., the use of hypo-osmolar
      irrigation). As a result, the risks of dilutional hyponatremia and transurethral
      resection (TUR) syndrome are eliminated, allowing for longer and safer resection.
      This review discusses the principles and applications of electrosurgery in
      conventional monopolar as well as new bipolar saline-based TURP systems. This
      review also addresses the positive impact on patient safety and resident
      training.

PMID- 18721043
TI  - Effect of skin-to-stone distance on shockwave lithotripsy success.
AB  - PURPOSE: We evaluated the effect of increased body habitus on stone-free rates
      after shockwave lithotripsy (SWL), determined by three reproducible skin-to-stone
      distances (SSDs) on CT. PATIENTS AND METHODS: We retrospectively reviewed the
      records of 85 patients with preoperative CT scans available on Stentor Radiology
      Imaging who underwent SWL with the unmodified Dornier HM3 lithotripter from 2002
      to 2007. SSDs were measured at the following angles: 0 degrees (vertical), 30
      degrees, and 90 degrees (horizontal). Successful therapy was defined as stone
      free (residual fragments <2 mm) on follow-up imaging. Data were analyzed using
      descriptive statistics, Student t test, and the Fisher exact test. RESULTS: Four
      hundred and eighty patients underwent SWL at our institution from 2002 to 2007;
      85 patients (50.6% men, mean age 50.8 +/- 15.7 years, mean body mass index [BMI]
      28.8 +/- 6.6 kg/m2) had preoperative CT scans available for review. On follow-up
      imaging (142.7 +/- 217.2 days), 49.4% of patients were stone free. Mean SSDs
      (vertical, 30 degrees, horizontal) in patients who were stone-free v those with
      residual stone were 104.3 +/- 26.2 mm v 102.6 +/- 29.9 mm (P = 0.79), 103.9 +/-
      28.2 mm v 101.0 +/- 31.5 mm (P = 0.66), and 106.6 +/- 25.3 mm v 107.1 +/- 29.3 mm
      (P = 0.94), respectively. CONCLUSIONS: Multiple variables have been shown to be
      associated with SWL success. In our sample of patients with preoperative CT
      scans, SSD was found to have no effect on SWL success.

PMID- 18721044
TI  - Is ureteral catheterization necessary after ureteroscopic lithotripsy for
      uncomplicated upper ureteral stones?

PMID- 18721045
TI  - Evaluation of the impact and need for use of a safety guidewire during
      ureteroscopy.
AB  - BACKGROUND AND PURPOSE: The routine use of a "safety" guidewire adjacent to the
      ureteroscope during upper tract endoscopy is advocated in surgical texts and by
      many endourologists. Our experience has led us to theorize that a safety
      guidewire complicates ureteroscopy by providing resistance to introduction of the
      endoscope and by creating an obstruction to ureteroscopic instrumentation. To
      examine our theory, we developed a porcine animal model to evaluate the impact of
      the presence of a safety guidewire and reviewed our clinical experience, which
      routinely does not use a safety guidewire during ureteroscopy. PATIENTS AND
      METHODS: An ex vivo model was created using the excised urinary tract of freshly
      slaughtered pigs. The forces needed to advance both a semirigid and flexible
      ureteroscope in the ureter were measured with and without the presence of a 0.035
      inch safety guidewire. The clinical records of all patients undergoing
      ureteroscopy over a 4-year period were reviewed. RESULTS: On average, an
      additional 12 and 20 g of force were needed to introduce the semirigid and
      flexible ureteroscope when a guidewire was present. For the chosen study period,
      361 patients underwent ureteroscopic procedures without the placement of a safety
      guidewire. No patient experienced an intraoperative complication related to the
      absence of a safety wire. CONCLUSIONS: The presence of a safety guidewire
      adjacent to the endoscope inhibits passage of the ureteroscope in an in vitro
      animal model. Technologic advancements in ureteroscope design and use of the
      holmium laser lithotrite minimize ureteral trauma and obviate the need for
      routine use of a safety wire during ureteroscopy.

PMID- 18721046
TI  - Another novel application of Hem-o-Lok clips for transient vascular occlusion in
      robot-assisted laparoscopic partial nephrectomy: an alternative to laparoscopic
      bulldog and Satinsky clamps.
AB  - We describe our technique of achieving transient vascular occlusion utilizing Hem
      o-Lok clips during robotassisted laparoscopic partial nephrectomy (RLPN) A once
      folded vascular loop is threaded through a 2-cm feeding tube. After passing
      around the renal vessel, its tail goes through the U-loop, creating a tourniquet.
      Vascular occlusion begins when the tube slides towards the vessel and a Hem-o-Lok
      clip is applied on the vascular loop next to the exposed end of the tube. When no
      longer needed, it is released. Since July 2006, 25 patients underwent RLPN
      utilizing this technique, which required <15 seconds to deploy for any vessel
      size. There were eight patients with multiple vessels. The mean operative time
      was 82.6 minutes, and the mean warm ischemia time was 22 minutes (range 17-27
      minutes). There were no cases of intraoperative or postoperative bleeding. The
      technique is simple, inexpensive, and applicable to multiple vessels. It is a
      viable alternative to standard vascular occlusion techniques, such as
      laparoscopic bulldog or Satinsky clamps.

PMID- 18721047
TI  - Laparoscopic extravesical ureteroneocystostomy by a new "Y" flap technique.
AB  - BACKGROUND AND PURPOSE: Laparoscopic ureteral implantation can be a challenging
      procedure. We describe a simple "Y" flap technique to facilitate laparoscopic
      ureteral implantation. METHODS: Three patients with distal ureteral strictures
      underwent laparoscopic ureteral reimplantation by a modified technique. Blunt
      dissection is used to mobilize 4 cm of the ureter. A neocystostomy is performed
      in the bladder and, after isolation of the ureter, it is bivalved for a length of
      1.5 cm, creating a Y flap. A 6 by 24 Double-J stent is placed intraoperatively,
      feeding it through the distal end of the ureter. The cut ends of the bivalved Y
      flaps of the ureter are anastomosed into the bladder by two simple pexic sutures.
      The ureter is advanced 1 cm from the neocystostomy to lay the Y flap into the
      bladder. RESULTS: After laparoscopic reimplantation using this new technique, all
      patients were studied postoperatively. None revealed any obstruction, as
      confirmed by intravenous urography at 1 month and diuretic renography at 3 months
      after removal of the stent. CONCLUSIONS: Laparoscopic ureteral reimplantation is
      feasible using a new Y flap technique with excellent functional and anatomic
      results.

PMID- 18721048
TI  - Viscoelastic property mapping along encrusted polymeric urinary catheters.
AB  - PURPOSE: Mapping of the material viscoelastic property variation along the length
      axis of polymeric stents. MATERIALS AND METHODS: Five pigtail ureteral stents and
      five percutaneous stents placed in vivo for different periods were studied.
      Viscoelastic property changes along the length of polymeric stents were measured
      using the dynamic mechanical analysis technique. The type of encrustations was
      identified using FT-IR spectroscopy and their morphology by scanning electron
      microscopy (SEM). RESULTS: Variations in viscoelastic stiffness were confirmed
      for both types of stents. In a few cases, the variation was quite large (400%).
      Various encrustation types and/or organic sheathing of the salt were found to be
      responsible for this effect. In detail, calcium oxalate monohydrate (COM) plaques
      for percutaneous and COM/organic layer for pigtail stents were recognized by FT
      IR spectroscopy and SEM observation to invoke reinforcing effects along the stent
      axes. CONCLUSIONS: The phenomenon of stiffness variation along the stent axes
      requires further study to understand the mechanism behind it and consequently to
      improve the biomaterial and design of specific areas of stents as well as to
      avoid encrustations. This further research might lead in the near future to the
      development of new types of polymer stents for drug-eluting specialized areas.

PMID- 18721049
TI  - Abstracts from the Eastern Asian Society of Endourology meeting, December 13-16,
      2007, Hong Kong.

PMID- 18721054
TI  - Acceptance of rapid HIV testing among medical inpatients in New York City.
AB  - Early diagnosis of HIV infection is important for both individual and public
      health. This study examined patient acceptability of routine, voluntary HIV
      testing in a New York City hospital serving East Harlem, a diverse community with
      an HIV seroprevalence of 2.6%. Consecutive admissions to the general medicine
      service were screened for enrollment between October 27 and November 22, 2005,
      and March 13 and May 9, 2006. Participants completed a self-administered printed
      survey and underwent rapid HIV testing. Of the 420 patients approached, 100
      patients participated. The most common reason for declining participation was, "I
      feel too sick to participate." Participants were more likely to be men (odds
      ratio [OR] 1.71, 95% confidence interval [CI] 1.05, 2.77) and to be in a younger
      age group (20-49 years; OR 2.70, 95% CI 1.64, 4.45). Participants who reported
      one or more HIV risk factors were not more likely to answer "Yes" when responding
      to the statement, "I have risk factors for HIV" compared to patients who did not
      report any specific clinical or behavioral HIV risk factors (OR = 1.16, 95% CI
      0.38,3.53). In addition, patients who reported one or more specific clinical
      and/or behavioral HIV risk factors were not more likely to have received prior
      HIV testing (OR = 1.58, 95% CI 0.58, 4.32). Three individuals were newly
      diagnosed with HIV/AIDS. Risk-based testing may be inadequate, as patients do not
      accurately assess risk and do not seek or accept testing based on risk. Routine,
      voluntary HIV testing is able to identify patients missed in the risk-based model
      of HIV testing, expanding the opportunities for timely diagnosis and
      intervention. In order to fully implement the new Centers for Disease Control and
      Prevention (CDC) recommendations for routine, voluntary testing, the optimal
      timing to offer HIV testing to acutely ill inpatients warrants further
      investigation.

PMID- 18721055
TI  - Labeling changes for abacavir.

PMID- 18721056
TI  - System review analyzes organ transplant success.

PMID- 18721058
TI  - Expression of the dengue virus type 2 NS5 protein in a CD4(+) T cell line
      inhibits HIV replication.
AB  - Human immunodeficiency virus (HIV) load is suppressed during dengue virus
      infection. The NS5A phosphoprotein of GB virus C (a related flavivirus) inhibits
      HIV replication in vitro. To determine whether the dengue virus NS5 protein
      inhibits HIV replication, CD4(+) T cell lines expressing this protein were
      generated. HIV replication in dengue virus NS5-expressing cells decreased by >90%
      compared with control cells (P < .01), and this was mediated in part by decreased
      HIV coreceptor (CXCR4) expression and increased production of SDF-1. Thus, the
      dengue virus NS5 protein inhibits HIV replication in vitro, potentially
      explaining the reduction in HIV load observed during acute dengue virus
      infection.

PMID- 18721059
TI  - Effects of flagellin on the functions of follicle-associated epithelium.
AB  - Bacterial flagellin activates innate immune responses by signaling through Toll
      like receptor 5 and is a potential vaccine adjuvant. Mucosal lymphoid follicles,
      inductive sites for adaptive mucosal immune responses, are covered by a follicle
      associated epithelium (FAE) specialized for the uptake of antigens. This study
      demonstrates that mucosal application of Salmonella dublin flagellin enhanced
      transepithelial transport of microparticles by the FAE of mouse Peyer's patches
      in vivo. Flagellin also induced rapid, matrix metalloproteinase-dependent
      migration of subepithelial dendritic cells (DCs) into the FAE, better positioning
      DCs for antigen capture. These innate responses to flagellin enhance FAE
      functions and may promote adaptive immune responses in the mucosa.

PMID- 18721060
TI  - Plasmodium falciparum and helminth coinfection in a semi urban population of
      pregnant women in Uganda.
AB  - BACKGROUND: Helminth infections and malaria are widespread in the tropics. Recent
      studies suggest helminth infections may increase susceptibility to Plasmodium
      falciparum infection. If confirmed, this increased susceptibility could be
      particularly important during pregnancy-induced immunosuppression. OBJECTIVE: To
      evaluate the geographical distribution of P. falciparum-helminth coinfection and
      the associations between P. falciparum infection and infection with various
      parasite species in pregnant women in Entebbe, Uganda. METHODS: A cross-sectional
      study was conducted at baseline during a trial of antihelminthic drugs during
      pregnancy. Helminth and P. falciparum infections were quantified in 2,507
      asymptomatic women. Subjects' socioeconomic and demographic characteristics and
      geographical details were recorded. RESULTS: Hookworm and Mansonella perstans
      infections were associated with P. falciparum infection, but the effect of
      hookworm infection was seen only in the absence of M. perstans infection. The
      odds ratio [OR] for P. falciparum infection, adjusted for age, tribe,
      socioeconomic status, HIV infection status, and location was as follows: for
      individuals infected with hookworm but not M. perstans, 1.53 (95% confidence
      interval [CI], 1.09-2.14); for individuals infected with M. perstans but not
      hookworm, 2.33 (95% CI, 1.47-3.69); for individuals infected with both hookworm
      and M. perstans, 1.85 (CI, 1.24-2.76). No association was observed between
      infection with Schistosoma mansoni, Trichuris, or Strongyloides species and P.
      falciparum infection. CONCLUSIONS: Hookworm-P. falciparum coinfection and M.
      perstans-P. falciparum coinfection among pregnant women in Entebbe is more common
      than would be expected by chance. Further studies are needed to elucidate the
      mechanism of this association. A helminth-induced increase in susceptibility to
      P. falciparum could have important consequences for pregnancy outcome and
      responses to P. falciparum infection in infancy.

PMID- 18721062
TI  - Tenofovir-associated decline in renal function.

PMID- 18721063
TI  - Pediatric highly active antiretroviral therapy in Africa: potential benefits of a
      family-centered model.

PMID- 18721065
TI  - Histo-blood group antigens and susceptibility to infection with norovirus
      genogroup II genotype 4.

PMID- 18721066
TI  - Association of histo-blood group antigens with susceptibility to norovirus
      infection may be strain-specific rather than genogroup dependent.

PMID- 18721067
TI  - Intital descriptive and analytical data on an outbreak of norovirus infection at
      marine corps recruit depot Parris Island, South Carolina.

PMID- 18721070
TI  - Non-viral delivery of the gene for glial cell line-derived neurotrophic factor to
      mesenchymal stem cells in vitro via a collagen scaffold.
AB  - Recent advances in tissue engineering that combine an extracellular matrix-like
      scaffold with therapeutic molecules, cells, DNA encoding therapeutic proteins, or
      a combination of the three hold promise for treating defects in the brain
      resulting from a penetrating injury or tumor resection. The purpose of this study
      was to investigate a porous sponge-like collagen scaffold for non-viral delivery
      of a plasmid encoding for glial cell line-derived neurotrophic factor (pGDNF) to
      rat marrow stromal stem cells (also referred to as mesenchymal stem cells, MSCs).
      The effects of the following parameters on GDNF synthesis in the three
      dimensional (3D) constructs were evaluated and compared with results in monolayer
      culture: initial plasmid load (2-50 microg pGDNF), ratio of a lipid transfection
      reagent to plasmid (5:10), culture environment during the transfection (static
      and dynamic), and cell density. The level of gene expression in the collagen
      scaffolds achieved therapeutic levels that had previously been found to support
      survival of dopaminergic and trigeminal neurons in vitro. For the highest loading
      of plasmid (50 microg), the level of GDNF protein remained six to seven times
      above the control level after 2 weeks, a significant difference. Cell density in
      the scaffold was of importance for an early increase in GDNF production, with
      accumulated GDNF being approximately 60% greater after 9 days of culture when
      scaffolds were initially seeded with 2 million rat MSCs compared to 500,000
      cells. Application of orbital shaking during the 4 h of transfection had a
      positive effect on the production of GDNF on 3D constructs but not of the same
      magnitude as reported in monolayer studies. Overall, these results demonstrate
      that the combination of tissue engineering and non-viral transfection of MSCs for
      the over-expression of GDNF is a promising approach for the long-term production
      of GDNF and probably for neurotrophic factors in general.

PMID- 18721071
TI  - The problem with nutritionally enhanced plants.
AB  - Among the next generation of genetically modified (GM) plants are those that are
      engineered to produce elevated levels of nutritional molecules such as vitamins,
      omega-3 fatty acids, and amino acids. Based upon the U.S. current regulatory
      scheme, the plants and their products may enter our food supply without any
      required safety testing. The potential risks of this type of GM plant are
      discussed in the context of human health, and it is argued that there should be
      very careful safety testing of plants designed to produce biologically active
      molecules before they are commercially grown and consumed. This will require a
      mandatory, scientifically rigorous review process.

PMID- 18721072
TI  - The influence of HER2 genotypes as molecular markers on breast cancer outcome.
AB  - Alterations of the human epidermal growth factor receptor 2 (HER2) protooncogene
      have been implicated in the carcinogenesis and prognosis of breast cancer. A
      polymorphism has been identified at codon 655 (ATC/isoleucine to GTC/valine
      [I655V]) in the transmembrane domain-coding region of this gene, which may be
      associated with the risk of breast cancer. In this study we aimed to determine
      whether the risk of breast cancer is associated with the I655V polymorphism of
      HER2 transmembrane domain-coding region at codon 655. The genomic DNA from breast
      cancer patients and control subjects underwent analysis by the polymerase chain
      reaction-fragment length polymorphism. We observed no overall association between
      HER2 genotype and breast cancer (p = 0.53). However, an elevated positive
      association was observed for Ile/Val+Val/Val versus Ile/Ile genotypes in women
      >age 60 years (p = 0.02). Further, other risk factors--namely, the body mass
      index and family history--were found to be risk factors for developing breast
      cancer (p = 0.006 and p = 0.00, respectively). In conclusion, results of this
      study suggest that polymorphisms of the HER2 gene may be important susceptibility
      biomarkers for breast cancer risk among older women.

PMID- 18721073
TI  - Effects of plasmid growth hormone-releasing hormone treatment during heat stress.
AB  - A gene therapy treatment with plasmid-based growth hormone-releasing hormone
      (GHRH) delivered by electroporation (EP) was investigated during heat stress; 32
      primiparous cows received 2.5 mg of a GHRH-expressing myogenic plasmid (pSP-HV
      GHRH), while 20 were designated as controls. Offspring of treated animals showed
      a reduction in mortality (47%; p < 0.02), and survival from birth to 260 days was
      dramatically improved (0% mortality vs. 21% in controls) along with an increase
      in weight gain (p < 0.05). Milk production was increased compared to controls
      with an average yield gain of 421 kg/cow (p = 0.028). Prolactin (PRL) levels were
      also significantly increased compared to controls (p < 0.05). The second
      pregnancy rate was improved by GHRH treatment (53.3% vs. 30.8%). This study shows
      that the use of plasmid-mediated therapy delivered by EP can maintain health
      status during periods of heat stress, important for both animals and potentially
      humans in hot, challenging climates.

PMID- 18721074
TI  - Differentiation of primary human submandibular gland cells cultured on basement
      membrane extract.
AB  - There is no effective treatment for the loss of functional salivary tissue after
      irradiation for head and neck cancer or the autoimmune disease Sjogren's
      syndrome. One possible approach is the regeneration of salivary glands from stem
      cells. The present study aimed to investigate whether small pieces of human
      submandiblar gland tissue contain elements necessary for the reconstruction of
      salivary rudiments in vitro via acinar and ductal cell differentiation. Primary
      submandibular gland (primary total human salivary gland; PTHSG) cells were
      isolated from human tissue and cultured in vitro using a new method in which
      single cells form an expanding epithelial monolayer on plastic substrates.
      Differentiation, morphology, number, and organization of these cells were then
      followed on basement membrane extract (BME) using RNA quantitation (amylase,
      claudin-1 (CLN1), CLN3, kallikrein, vimentin), immunohistochemistry (amylase and
      occludin), viability assay, and videomicroscopy. On the surface of BME, PTHSG
      cells formed acinotubular structures within 24 h, did not proliferate, and
      stained for amylase. In cultures derived from half of the donors, the acinar
      markers amylase and CLN3 were upregulated. The PTHSG culture model suggests that
      human salivary gland may be capable of regeneration via reorganization and
      differentiation and that basement membrane components play a crucial role in the
      morphological and functional differentiation of salivary cells.

PMID- 18721075
TI  - A continued commitment to quality research in tissue engineering.

PMID- 18721076
TI  - Application of high-mobility-group-A proteins increases the proliferative
      activity of chondrocytes in vitro.
AB  - The low capability of self-repair in hyaline cartilage tissue and chondrocytes de
      differentiating when grown in vitro (e.g., for tissue engineering approaches)
      limits articular cartilage repair. It has been shown that the embryonic
      architectural transcription factors of the high-mobility-group-A (HMGA) protein
      family affect the regulation of cell differentiation by influencing the state of
      cell chromatin and are involved in hyaline cartilage development by affecting the
      expression of chondrocyte-specific marker genes. Thus, the control of cartilage
      cell proliferation and differentiation by HMGA proteins promises to be an
      important aspect in cartilage tissue repair. To elucidate the effects on the
      proliferative activity of hyaline chondrocytes, HMGA proteins were recombinantly
      expressed, highly purified, and applied to porcine hyaline cartilage cells
      growing in in vitro monolayer cell culture. Direct application of HMGA1a, HMGA1b,
      and HMGA2 proteins onto porcine chondrocytes was shown to have a highly
      significant influence on cell proliferation. Greater proliferation of
      chondrocytes was achieved than in the untreated control group, indicating a
      promising approach to enhancing cartilage tissue repair.

PMID- 18721078
TI  - Effect of acupuncture in a patient with 7-year-history of Bell's palsy.
AB  - OBJECTIVES: To demonstrate the effect of acupuncture in a child with chronic
      Bell's palsy of 7 years duration. SUBJECT: A 15-year-old girl had Bell's palsy
      for 7 years and did not respond to steroid treatment in the acute phase. On
      examination, her eyes were asymmetric, with the right eye smaller. Muscle
      contracture was noted around the right nasalis. She had synkinesis (i.e., when
      she blinked, there was involuntary twitching of her mouth at the right side). She
      showed marked facial distortion when puffing out cheeks, smiling, and raising her
      eyebrows. The tip of her tongue was swollen with red spikes. House-Brackmann
      facial nerve grading system (HBS) before treatment was grade 4. TREATMENT:
      Patient was given 25 acupuncture treatment sessions in 2 months. Local
      acupuncture points used were: LI20, ST2, ST3, ST4, ST6, ST7, SI18, BL2, TE17,
      TE23, GB14, GV26, CV24, EX-HN5, and EX-HN16; distant points used were: LI11,
      ST36, ST40, SP6, SP10, HT8, SI3, BL67, PC8, TE5, and LR3. About 10 points were
      selected from the above set in each session with needles inserted to elicit the
      de qi response. The patient was asked to report any change in muscle strength or
      any differences noted after each acupuncture session. Photographs and videos were
      taken for blind assessors to comment on. RESULT: The patient rated an overall
      improvement of 60-70%. Self-perceived muscle strength when smiling and puffing
      out cheeks increased from 20% of normal strength to 65%, and the strength when
      raising eyebrows increased from 10% to 70%. Synkinesis was attenuated.
      Photographs and videos showed improvement in facial asymmetry. HBS changed to
      grade 3 after treatment. CONCLUSIONS: Our study showed that acupuncture can be
      effective in improving functional and cosmetic outcome even for chronic Bell's
      palsy.

PMID- 18721077
TI  - The role of lipase and alpha-amylase in the degradation of starch/poly(epsilon
      caprolactone) fiber meshes and the osteogenic differentiation of cultured marrow
      stromal cells.
AB  - The present work studies the influence of hydrolytic enzymes (alpha-amylase or
      lipase) on the degradation of fiber mesh scaffolds based on a blend of starch and
      poly(epsilon-caprolactone) (SPCL) and the osteogenic differentiation of
      osteogenic medium-expanded rat bone marrow stromal cells (MSCs) and subsequent
      formation of extracellular matrix on these scaffolds under static culture
      conditions. The biodegradation profile of SPCL fiber meshes was investigated
      using enzymes that are specifically responsible for the enzymatic hydrolysis of
      SPCL using concentrations similar to those found in human serum. These
      degradation studies were performed under static and dynamic conditions. After
      several degradation periods (3, 7, 14, 21, and 30 days), weight loss measurements
      and micro-computed tomography analysis (specifically porosity, interconnectivity,
      mean pore size, and fiber thickness) were performed. The SPCL scaffolds were
      seeded with rat MSCs and cultured for 8 and 16 days using complete osteogenic
      media with and without enzymes (alpha-amylase or lipase). Results indicate that
      culture medium supplemented with enzymes enhanced cell proliferation after 16
      days of culture, whereas culture medium without enzymes did not. No calcium was
      detected in groups cultured with alpha-amylase or without enzymes after each time
      period, although groups cultured with lipase presented calcium deposition after
      the eighth day, showing a significant increase at the sixteenth day. Lipase
      appears to positively influence osteoblastic differentiation of rat MSCs and to
      enhance matrix mineralization. Furthermore, scanning electron microscopy images
      showed that the enzymes did not have a deleterious effect on the three
      dimensional structure of SPCL fiber meshes, meaning that the scaffolds did not
      lose their structural integrity after 16 days. Confocal micrographs have shown
      cells to be evenly distributed and infiltrated within the SPCL fiber meshes up to
      410 microm from the surface. This study demonstrates that supplementation of
      culture media with lipase holds great potential for the generation of bone tissue
      engineering constructs from MSCs seeded onto SPCL fiber meshes, because lipase
      enhances the osteoblastic differentiation of the seeded MSCs and promotes matrix
      mineralization without harming the structural integrity of the meshes over 16
      days of culture.

PMID- 18721079
TI  - A single-blinded, randomized pilot study evaluating effects of electroacupuncture
      in diabetic patients with symptoms suggestive of gastroparesis.
AB  - BACKGROUND AND OBJECTIVES: The current pharmacological management of diabetic
      gastroparesis remains difficult. Acupuncture has been widely used for
      gastrointestinal symptoms. The aim of this study was to investigate the effects
      of electroacupuncture (EA) on solid gastric emptying time, serum gastrin,
      motilin, pancreatic polypeptide (PP), fasting and postprandial blood glucose, and
      symptoms in patients with diabetic gastroparesis. INTERVENTIONS: EA at the
      Zusanli (ST 36) and Hegu (LI 4) points and sham EA as control were administered
      by an experienced and licensed acupuncturist. DESIGN: This was a pilot study with
      a randomized, single-blinded design. SUBJECTS AND SETTING: Nineteen (19) patients
      with type 2 diabetes who had had symptoms of gastroparesis for more than 3 months
      were included in the trial and randomized into two groups. Each group received EA
      (n = 9) or sham EA (n = 10) consisting of 4 sessions over 2 weeks. OUTCOME
      MEASURES: Symptom severity was evaluated using the Gastroparesis Cardinal Symptom
      Index (GCSI) at baseline, at the end of treatment, and 2 weeks after the end of
      the trial; solid-phase gastric half-emptying time was measured by scintigraphy;
      in addition, serum gastrin, motilin, PP, fasting, and postprandial blood glucose
      levels were also measured. RESULTS: Gastric half-emptying time in 9 patients with
      diabetic gastroparesis was significantly shortened by EA treatment (143.8 +/-
      55.9 minutes versus 98.8 +/- 28.6 minutes, p < 0.03). Half-emptying time did not
      change (98.9 +/- 26.4 minutes versus 90.9 +/- 24.8 minutes, p > 0.05) in the sham
      EA group. Symptom severity, as measured by GCSI total score, improved
      significantly both at the end of treatment (2.38 +/- 0.56 versus 1.48 +/- 0.19, p
      < 0.001) and 2 weeks after the end of the trial (2.38 +/- 0.56 versus 1.65 +/-
      0.44, p < 0.01) when compared with the baseline in the EA group, but did not
      change from baseline with sham EA treatment. There were no significant changes in
      fasting and postprandial blood glucose, serum gastrin, motilin, and PP in both
      groups. No significant adverse events occurred. CONCLUSIONS: This study
      demonstrates that short-term EA at the Zusanli and Hegu points effectively
      reduces the dyspeptic symptoms of diabetic gastroparesis and accelerates solid
      gastric emptying. Sustained improvement in dyspeptic symptoms was observed at 2
      weeks after the end of the trial. Its potential for treating gastroparesis may be
      explored, and a larger trial is required to draw definitive conclusions.

PMID- 18721080
TI  - Treatment of post-stroke depression with antidepressants.

PMID- 18721082
TI  - An integrative medicine patient care model and evaluation of its outcomes: the
      University of Michigan experience.
AB  - BACKGROUND: The demand for integrative medicine care is increasing rapidly among
      patient consumers, yet the integrative medicine model is not the norm in clinical
      practice, nor is this approach a focus in traditional medical schools.
      Furthermore, patient well-being and satisfaction outcomes within an integrative
      care model are not common in the literature. OBJECTIVES: The purpose of this
      paper is to offer a summary of a model of integrative medicine patient care and
      its evaluation and outcomes from the University of Michigan Integrative Medicine
      Clinic. METHODS: Using three tools to evaluate patient outcomes and satisfaction,
      statistically significant outcomes were noted. The SF-12 showed positive change
      in the physical component score, the Holistic Health Questionnaire showed
      improvements in all of the subscales of body, mind, and spirit, and a unique
      Integrative Medicine Patient Satisfaction Tool suggested high satisfaction with
      an integrative approach to care. CONCLUSIONS: Findings, limitations, and
      implications are discussed.

PMID- 18721083
TI  - Complementary and alternative medicine use in Turkish children with bronchial
      asthma.

PMID- 18721084
TI  - Effect of T'ai chi chuan training on cardiovascular risk factors in dyslipidemic
      patients.
AB  - OBJECTIVE: T'ai chi chuan (TCC) is a traditional Chinese exercise and is
      beneficial for health. Nevertheless, its effect on cardiovascular risk factors in
      dyslipidemic patients is not clear. The aim of this study was to evaluate the
      effect of TCC training on coronary heart disease (CHD) risk factors in patients
      with dyslipidemia. DESIGN: This was designed as a case-controlled study. SETTING:
      The study was conducted in a community setting. SUBJECTS: Fifty-three (53)
      patients (males: 24; females: 29) with dyslipidemia completed this study.
      INTERVENTIONS: The TCC group included 28 patients who participated in a 12-month
      yang TCC training program. The usual-care group included 25 patients who
      maintained a sedentary lifestyle during this study. OUTCOME MEASURES: Exercise
      testing was conducted at baseline and after 1 year of training. Body composition,
      lipid profile, fasting glucose and insulin levels, and inflammatory markers were
      also measured before and after training. RESULTS: After training, the TCC group
      showed an increase in V(.)O(2peak) from 25.2 +/- 4.2 to 27.4 +/- 4.1 mL x kg(1) x
      min(1); while the usual-care group displayed a significant decrease from 25.6 +/-
      4.9 to 24.1 +/- 4.0 mL x kg(-1) x min(-1). The TCC group also showed a reduction
      in blood pressure, triglyceride, total cholesterol, low density lipoprotein
      cholesterol, plasma insulin, homeostasis model assessment index, and high
      sensitivity C-reactive protein. Conversely, the usual-care group showed no
      significant improvement in these cardiovascular risk factors. CONCLUSIONS: A 12
      month TCC training program significantly improves aerobic capacity and CHD risk
      factors in patients with dyslipidemia.

PMID- 18721085
TI  - The beneficial effects of the herbal medicine Free and Easy Wanderer Plus (FEWP)
      and fluoxetine on post-stroke depression.
AB  - OBJECTIVES: Depression occurs frequently in post-stroke patients and appears to
      be associated with impairment of their rehabilitation and functional recovery. In
      this study, we evaluated the efficacy and tolerability of the herbal drug, Free
      and Easy Wanderer Plus (FEWP), in patients affected by post-stroke depression
      (PSD). METHODS: One hundred fifty (150) moderately to severely depressed patients
      as determined by a score >20 on the Hamilton Depression Scale (HDS) after a
      single ischemic or hemorrhagic stroke were randomly divided into the FEWP group
      (n = 60), the fluoxetine group (n = 60), and the placebo group (n = 30). The
      FEWP, fluoxetine, and placebo were administered to the patients over a period of
      8 weeks. Depression was evaluated by HDS and the Barthel Index (BI) before,
      during, and after the treatment. RESULTS: Significantly higher clinical response
      rates were observed in both the FEWP and fluoxetine groups compared to the
      placebo group (60% and 65.5% versus 21.4%, chi(2) = 15.9, p < 0.01) and there was
      no difference in the response rates between the FEWP group and the fluoxetine
      group at the end of this study (60% versus 65.5%, chi(2) = 0.38, p > 0.05).
      Compared to fluoxetine, FEWP produced significantly greater improvement in
      depression at week 2 (15% versus 3.3%, chi(2) = 4.9, p < 0.05). Furthermore, FEWP
      produced significantly greater improvement in the activities of daily living
      (ADL) than fluoxetine at the end of this trial (BI: 43.8 +/- 5.6 versus 40.7 +/-
      3.7, p < 0.01). CONCLUSIONS: FEWP showed good efficacy, safety, and tolerability
      in PSD patients. We conclude that FEWP is well tolerated and may be a useful
      therapeutic option in patients with PSD.

PMID- 18721086
TI  - Deindividuation and Internet software piracy.
AB  - Computer crime has increased exponentially in recent years as hardware, software,
      and network resources become more affordable and available to individuals from
      all walks of life. Software piracy is one prevalent type of cybercrime and has
      detrimentally affected the economic health of the software industry. Moreover,
      piracy arguably represents a rend in the moral fabric associated with the respect
      of intellectual property and reduces the financial incentive of product creation
      and innovation. Deindividuation theory, originating from the field of social
      psychology, argues that individuals are extricated from responsibility for their
      actions simply because they no longer have an acute awareness of the identity of
      self and of others. That is, external and internal constraints that would
      typically regulate questionable behavior are rendered less effective via certain
      anonymizing and disinhibiting conditions of the social and environmental context.
      This exploratory piece seeks to establish the role of deindividuation in
      liberating individuals to commit software piracy by testing the hypothesis that
      persons who prefer the anonymity and pseudonymity associated with interaction on
      the Internet are more likely to pirate software. Through this research, it is
      hoped that the empirical identification of such a social psychological
      determinant will help further illuminate the phenomenon.

PMID- 18721087
TI  - Product placement of computer games in cyberspace.
AB  - Computer games are considered an emerging media and are even regarded as an
      advertising channel. By a three-phase experiment, this study investigated the
      advertising effectiveness of computer games for different product placement
      forms, product types, and their combinations. As the statistical results
      revealed, computer games are appropriate for placement advertising. Additionally,
      different product types and placement forms produced different advertising
      effectiveness. Optimum combinations of product types and placement forms existed.
      An advertisement design model is proposed for use in game design environments.
      Some suggestions are given for advertisers and game companies respectively.

PMID- 18721089
TI  - Involving persons with dementia in the evaluation of outdoor environments.
AB  - Using virtual reality (VR), we examined the barriers to and facilitators of
      functioning outdoors in persons with dementia (PwD) and investigated the
      generalizability of findings in VR to the real world. An existing town center was
      modeled in VR. PwD took part in both real-world and VR walks. Based on the
      results, the model was redesigned and then tested again. Performance on the walks
      improved, and potentially beneficial adaptations to outdoor environments were
      identified, but limitations of VR as a representation of the real world were also
      identified. We conclude that VR models, together with a rigorous behavioral
      testing method, can be a useful tool for the evaluation of outdoor environments
      and for identifying improvements for PwD.

PMID- 18721088
TI  - Developing and validating an instrument for measuring mobile computing self
      efficacy.
AB  - IT-related self-efficacy has been found to have a critical influence on system
      use. However, traditional measures of computer self-efficacy and Internet-related
      self-efficacy are perceived to be inapplicable in the context of mobile computing
      and commerce because they are targeted primarily at either desktop computer or
      wire-based technology contexts. Based on previous research, this study develops
      and validates a multidimensional instrument for measuring mobile computing self
      efficacy (MCSE). This empirically validated instrument will be useful to
      researchers in developing and testing the theories of mobile user behavior, and
      to practitioners in assessing the mobile computing self-efficacy of users and
      promoting the use of mobile commerce systems.

PMID- 18721090
TI  - Visual attention during virtual social situations depends on social anxiety.
AB  - Theories of anxiety propose that people with phobias involuntarily allocate their
      attention first toward threatening stimuli and then away from these stimuli.
      Therefore, the current study assessed attention toward and away of social cues in
      virtual fear-relevant situations. More specifically, open visual attention was
      assessed by means of electroocculogram (EOG)-based eye-tracking combined with
      head-tracking. Participants viewed virtual persons with different facial
      expressions (happy or angry) in a free-viewing virtual elevator situation. Twenty
      six students participated in the study. Actual anxiety was induced to half of
      them by announcing that they had to give a talk after leaving the virtual
      elevator. Habitual social anxiety was assessed by questionnaires. Results
      indicate that participants initially attended more to happy than to angry virtual
      persons, and participants who expected to give a talk afterwards were especially
      likely to sustain attending to the happy virtual persons and avoiding the angry
      persons. Correlation analyses revealed that higher social anxiety was positively
      related to initial avoidance of happy and angry virtual persons. Thus, higher
      socially anxious participants seem to initially avoid emotional facial
      expressions. These results confirm the assumption that faces are especially
      meaningful for socially anxious people but contradict findings of an open initial
      hypervigilance toward threatening stimuli. The results indicate that virtual
      social situations are especially suitable to measure overt attention in an
      ecologically valid environment.

PMID- 18721091
TI  - Enhancing computing skills of low-achieving students via e-learning: a design
      experiment of Web-based, problem-based learning and self-regulated learning.
AB  - A design experiment was conducted applying Web-based problem-based learning
      (PBL), self-regulated learning (SRL), or their combination to help low-achieving
      students improve their skills of deploying application software in a compulsory
      course at a vocational school in Taiwan. The effects were encouraging and mostly
      positive. However, students' inertia to change routines of learning inherited
      from a culture of taking standard tests found in e-learning practice is quite
      common. A teacher's awareness of these changes and associated resistance may
      increase likelihood of e-learning success for future trials. Some modifications
      of the design are thus suggested for the next round of the experiment.

PMID- 18721092
TI  - Race, gender, and information technology use: the new digital divide.
AB  - This research examined race and gender differences in the intensity and nature of
      IT use and whether IT use predicted academic performance. A sample of 515
      children (172 African Americans and 343 Caucasian Americans), average age 12
      years old, completed surveys as part of their participation in the Children and
      Technology Project. Findings indicated race and gender differences in the
      intensity of IT use; African American males were the least intense users of
      computers and the Internet, and African American females were the most intense
      users of the Internet. Males, regardless of race, were the most intense videogame
      players, and females, regardless of race, were the most intense cell phone users.
      IT use predicted children's academic performance. Length of time using computers
      and the Internet was a positive predictor of academic performance, whereas amount
      of time spent playing videogames was a negative predictor. Implications of the
      findings for bringing IT to African American males and bringing African American
      males to IT are discussed.

PMID- 18721093
TI  - Frames and knowledge in mixed media: how activation changes information intake.
AB  - Many people consider strategic framing, the journalistic tendency to reduce
      politics to a game or competition focused on the tactical maneuvers of political
      actors, to be harmful to democracy because it erodes citizen interest in the
      democratic process. Our results demonstrate that this is not always the case.
      Testing the effects of textual strategic frames and video processing in a digital
      environment, we show that strategic frames may also provide a context that is
      more conducive to learning in mixed media news environments than that provided by
      value frames, those focused on the value conflict between principled policy
      opponents. Further analysis reveals that this effect is most clearly seen among
      people who read political blogs (i.e., those who are already active and
      interested in politics). Our data suggest that for individuals with cognitive
      networks built around ideological concerns, such as blog readers, value-framed
      messages provide cues to stop encoding new information, while strategically
      framed messages lead people to continue absorbing and learning in mixed media
      environments.

PMID- 18721094
TI  - The role of positive/negative outcome expectancy and refusal self-efficacy of
      Internet use on Internet addiction among college students in Taiwan.
AB  - Based on Bandura's social cognitive theory, this study was designed to examine
      positive and negative outcome expectancy and refusal self-efficacy of Internet
      use and their contribution to Internet addiction among college students by using
      hierarchical multiple regression analyses in a cross-sectional study design.
      Schools were first stratified into technical or nontechnical colleges and then
      into seven majors. A cluster random sampling by department was further applied to
      randomly choose participants from each major. A representative sample of 4,456
      college students participated in this study. The Outcome Expectancy and Refusal
      Self-Efficacy of Internet Use Questionnaire and the Chen Internet Addiction Scale
      were used to assess the cognitive factors and the levels of Internet addiction.
      Results showed that both positive outcome expectancy and negative outcome
      expectancy were significantly and positively correlated with Internet addiction,
      and refusal self-efficacy of Internet use was significantly and negatively
      related to Internet addiction. Further analyses revealed that refusal self
      efficacy of Internet use directly and negatively predicted Internet addiction.
      Moreover, we discovered that positive outcome expectancy positively predicted
      Internet addiction via refusal self-efficacy of Internet use; however,
      surprisingly, negative outcome expectancy had both a direct and indirect positive
      relationship in predicting Internet addiction via the refusal self-efficacy of
      Internet use. These results give empirical evidence to verify the theoretical
      effectiveness of the three cognitive factors to Internet addiction and should be
      incorporated when designing prevention programs and strategies for Internet
      addicted college students.

PMID- 18721095
TI  - University students' Internet use and its relationships with academic
      performance, interpersonal relationships, psychosocial adjustment, and self
      evaluation.
AB  - This study examined the relationships between university students' Internet use
      and students' academic performance, interpersonal relationships, psychosocial
      adjustment, and self-evaluation. The study was based on data drawn from a
      national survey of college students in Taiwan. A stratified sample of 49,609
      students (2005-2006 academic year juniors) was randomly selected from 156
      universities (174,277 students). Students completed a questionnaire online. Heavy
      Internet users and nonheavy Internet users differed significantly on a number of
      dimensions. Nonheavy users had better relationships with administrative staff,
      academic grades, and learning satisfaction than heavy Internet users. Heavy users
      were more likely than non-heavy Internet users to be depressed, physically ill,
      lonely, and introverted.

PMID- 18721096
TI  - Sex differences in spatial object-location memory in a virtual grocery store.
AB  - The grocery shopping Virtual Reality Spatial Object-Location Test (VRSOLT) was
      developed to examine sex differences in spatial object-location memory in a 3D
      virtual environment that simulates the real world. Forty college students (20
      males, 20 females) were tested on the VRSOLT as well as mental rotation and 2D
      object-location memory tasks. Both convergent and divergent validity was
      demonstrated. Males showed an advantage on mental rotation, and results of the
      VRSOLT grocery store test replicated the female object-location advantage seen in
      2D tests. A strategy of systematically navigating the environment may aid female
      encoding for object location.

PMID- 18721097
TI  - E-health for older people: the use of technology in health promotion.
AB  - To meet the needs of frail older people and to promote functional longevity,
      providing health education and disease prevention to the elderly is important.
      The present study describes the development, implementation, and evaluation of an
      e-health program for older persons. The objective of the 4-week e-health program
      was to improve elders' autonomous access to and use of health-related information
      in the form of physical exercise videography from a government-sponsored Web
      site. The content of the program included participants' mastery of basic
      computing skills and accessing and enhancing participants' interest in seeking
      health-related knowledge and information via the Internet. Data were collected in
      weeks 1 (pretest) and 4 (posttest) using questionnaires and open-ended questions.
      Thirty older people participated in the study (9 males, 21 females, aged 65-80
      years, with the mean age of 72). Participants' mastery of basic computer
      operating skills increased significantly (p < 0.05); they were able to access
      health information via the Internet and had gained health-related knowledge by
      week 4 posttest (p < 0.05). The overall learning experience was positive. In
      conclusion, the collaboration of community partners in sponsoring a technology
      based e-health program would be an effective way to provide health education to
      older people.

PMID- 18721098
TI  - Problematic usage among highly-engaged players of massively multiplayer online
      role playing games.
AB  - One popular facet of Internet gaming is the massively multiplayer online role
      playing game (MMORPG). Some individuals spend so much time playing these games
      that it creates problems in their lives. This study focused on players of World
      of Warcraft. Factor analysis revealed one factor related to problematic usage,
      which was correlated with amount of time played, and personality characteristics
      of agreeableness, conscientiousness, neuroticism, and extraversion.

PMID- 18721099
TI  - Gender differences in relationships of actual and virtual social support to
      Internet addiction mediated through depressive symptoms among college students in
      Taiwan.
AB  - This study examined gender differences in the relationships of actual and virtual
      social support to Internet addiction mediated through depressive symptoms among
      college students in Taiwan. Results revealed that in females, both actual and
      virtual social support directly predicted Internet addiction or were mediated
      through depressive symptoms. However, in males, while Internet addiction was
      predicted by virtual social support directly or indirectly mediated through
      depressive symptoms, the link of actual social support to Internet addiction was
      only mediated through depressive symptoms. Furthermore, in both genders, lower
      actual social support and higher virtual social support were associated with
      higher depressive symptoms.

PMID- 18721100
TI  - Defining cyberbullying: a qualitative research into the perceptions of
      youngsters.
AB  - Data from 53 focus groups, which involved students from 10 to 18 years old, show
      that youngsters often interpret "cyberbullying" as "Internet bullying" and
      associate the phenomenon with a wide range of practices. In order to be
      considered "true" cyberbullying, these practices must meet several criteria. They
      should be intended to hurt (by the perpetrator) and perceived as hurtful (by the
      victim); be part of a repetitive pattern of negative offline or online actions;
      and be performed in a relationship characterized by a power imbalance (based on
      "real-life" power criteria, such as physical strength or age, and/or on ICT
      related criteria such as technological know-how and anonymity).

PMID- 18721101
TI  - Experimental comparisons of face-to-face and anonymous real-time team competition
      in a networked gaming learning environment.
AB  - This study investigates the impact of anonymous, computerized, synchronized team
      competition on students' motivation, satisfaction, and interpersonal
      relationships. Sixty-eight fourth-graders participated in this study. A
      synchronous gaming learning system was developed to have dyads compete against
      each other in answering multiple-choice questions set in accordance with the
      school curriculum in two conditions (face-to-face and anonymous). The results
      showed that students who were exposed to the anonymous team competition condition
      responded significantly more positively than those in the face-to-face condition
      in terms of motivation and satisfaction at the 0.050 and 0.056 levels
      respectively. Although further studies regarding the effects of anonymous
      interaction in a networked gaming learning environment are imperative, the
      positive effects detected in this preliminary study indicate that anonymity is a
      viable feature for mitigating the negative effects that competition may inflict
      on motivation and satisfaction as reported in traditional face-to-face
      environments.

PMID- 18721102
TI  - "They may be pixels, but they're MY pixels:" developing a metric of character
      attachment in role-playing video games.
AB  - This paper proposes a new and reliable metric for measuring character attachment
      (CA), the connection felt by a video game player toward a video game character.
      Results of construct validity analyses indicate that the proposed CA scale has a
      significant relationship with self-esteem, addiction, game enjoyment, and time
      spent playing games; all of these relationships are predicted by theory.
      Additionally, CA levels for role-playing games differ significantly from CA
      levels of other character-driven games.

PMID- 18721104
TI  - PRESENCCIA--Presence: Research Encompassing Sensory Enhancement,neuroscience,
      Cerebral-computer Interfaces and Applications.

PMID- 18721106
TI  - Inhibition of NR2B phosphorylation restores alterations in NMDA receptor
      expression and improves functional recovery following traumatic brain injury in
      mice.
AB  - Traumatic brain injury (TBI) triggers a massive glutamate efflux, hyperactivation
      of N-methyl-D-aspartate receptors (NMDARs) and neuronal cell death. Previously it
      was demonstrated that, 15 min following experimentally induced closed head injury
      (CHI), the density of activated NMDARs increases in the hippocampus, and
      decreases in the cortex at the impact site. Here we show that CHI-induced
      alterations in activated NMDARs correlate with changes in the expression levels
      of the major NMDARs subunits. In the hippocampus, the expression of NR1, NR2A,
      and NR2B subunits as well as the GluR1 subunit of the AMPA receptor (AMPAR) were
      increased, while in the cortex at the impact site, we found a decrease in the
      expression of these subunits. We demonstrate that CHI-induced increase in the
      expression of NMDAR subunits and GluR1 in the hippocampus, but not in the cortex,
      is associated with an increase in NR2B tyrosine phosphorylation. Furthermore,
      inhibition of NR2B-phosphorylation by the tyrosine kinase inhibitor PP2 restores
      the expression of this subunit to its normal levels. Finally, a single injection
      of PP2, prior to the induction of CHI, resulted in a significant improvement in
      long-term recovery of motor functions observed in CHI mice. These results provide
      a new mechanism by which acute trauma contributes to the development of secondary
      damage and functional deficits in the brain, and suggests a possible role for Src
      tyrosine kinase inhibitors as preoperative therapy for planned neurosurgical
      procedures.

PMID- 18721107
TI  - Macro-architectures in spinal cord scaffold implants influence regeneration.
AB  - Biomaterial scaffold architecture has not been investigated as a tunable source
      of influence on spinal cord regeneration. This study compared regeneration in a
      transected spinal cord within various designed-macro-architecture scaffolds to
      determine if these architectures alone could enhance regeneration. Three
      dimensional (3-D) designs were created and molds were built on a 3-D printer.
      Salt-leached porous poly(epsilon-caprolactone) was cast in five different macro
      architectures: cylinder, tube, channel, open-path with core, and open-path
      without core. The two open-path designs were created in this experiment to
      compare different supportive aspects of architecture provided by scaffolds and
      their influence on regeneration. Rats received T8 transections and implanted
      scaffolds for 1 and 3 months. Overall morphology and orientation of sections were
      characterized by H&E, luxol fast blue, and cresyl violet staining. Borders
      between intact gray matter and non-regenerated defect were observed from GFAP
      immunolabeling. Nerve fibers and regenerating axons were identified with Tuj-1
      immunolabeling. The open-path designs allowed extension of myelinated fibers
      along the length of the defect both exterior to and inside the scaffolds and
      maintained their original defect length up to 3 months. In contrast, the
      cylinder, tube, and channel implants had a doubling of defect length from
      secondary damage and large scar and cyst formation with no neural tissue
      bridging. The open-path scaffold architectures enhanced spinal cord regeneration
      compared to the three other designs without the use of biological factors.

PMID- 18721108
TI  - Effect of cervical dorsolateral funiculotomy on reach-to-grasp function in the
      rat.
AB  - Cervical spinal cord injury (SCI) can severely impair reaching and grasping
      ability, and several descending systems, including the rubrospinal tract and
      corticospinal tract, have been implicated in the control of reach-to-grasp
      movements. The primary aim of this study was to characterize further the forelimb
      deficits associated with a cervical dorsolateral funiculotomy, which ablates the
      rubrospinal tract but spares the dorsal and ventral corticospinal tract in the
      rat. Adult female rats that preferred to use their right forelimb to reach for
      single pellets received a lesion to the right cervical dorsolateral funiculus
      between the C3-4 dorsal roots. Gross forelimb motor function was assessed by
      measuring spontaneous forelimb usage during exploration in a cylinder, and fine
      motor function was assessed using staircase and single pellet reaching tests.
      Single pellet reaching was further evaluated by qualitative and quantitative
      kinematic scoring of the movement components. Histological analysis included the
      quantification of spared white matter. Cervical dorsolateral funiculotomy
      produced marked deficits in reaching performance on both the single pellet and
      staircase reaching tests, with transient deficits in gross forelimb usage in the
      cylinder. Quantitative kinematics also revealed a reduction in digit abduction
      during the reach, which persisted throughout the 8-week post-SCI period. Tests of
      reach-to-grasp function, therefore, were more sensitive than a test of gross
      forelimb usage after cervical dorsolateral funiculotomy and did not show recovery
      over the 8-week survival period. We suggest that the staircase test is a useful
      screening tool for intervention studies because of its ease of implementation,
      and that the single pellet test is valuable for examining reaching accuracy and
      detailed kinematics.

PMID- 18721109
TI  - Whole body physiologically-based pharmacokinetic models: their use in clinical
      drug development.
AB  - BACKGROUND: Whole-body physiologically-based pharmacokinetic (WB-PBPK) models
      mathematically describe an organism as a closed circulatory system consisting of
      compartments that represent the organs important for compound absorption,
      distribution, metabolism and elimination. OBJECTIVES: To review the current state
      of WB-PBPK model use in the clinical phases of drug development. METHODS: A
      qualitative description of the WB-PBPK model structure is included along with a
      review of the varying methods available for input parameterisation. Current and
      potential WB-PBPK model application in clinical development is discussed.
      CONCLUSIONS: This modelling tool is at present used for small and large molecule
      drug development primarily as a means to scale pharmacokinetics from animals to
      humans based on physiology. The pharmaceutical industry is active in employing
      these models to clinical drug development although the applications in use now
      are narrow in comparison to the potential. Expanded integration of WB-PBPK models
      into the drug development process will only be achieved with staff training,
      managerial will, success stories and regulatory agency openness.

PMID- 18721111
TI  - In silico prediction of substrate properties for ABC-multidrug transporters.
AB  - Overexpression of ABC (ATP-binding cassette)-type drug efflux pumps, such as
      ABCB1, ABCC1 and ABCG2 in cancer cells confers multi-drug resistance (MDR) and
      represents a major cause of treatment failures in cancer therapy. Furthermore,
      there is increasing evidence for the important contribution of ABC-transporters
      to bioavailability, distribution, elimination and blood-brain barrier permeation
      of drug candidates. This review presents an overview on the different
      computational methods and models pursued to predict ABC-transporter substrate
      properties of drug-like compounds. They range from linear discriminant analysis
      to pharmacophore modelling and machine learning algorithms. Many of these models
      show a satisfying performance within the study-specific, defined chemical space
      but general applicability for the whole drug-like chemical space still needs to
      be proven. First attempts aiming towards selectivity profiling for ligands of the
      two polyspecific transporters ABCB1 and ABCG2 is also discussed. This might pave
      the way for a pharmacological profiling of compound series with special focus on
      their ADMET (absorption, distribution, metabolism, excretion and toxicity)
      properties.

PMID- 18721110
TI  - Modifications of human carboxylesterase for improved prodrug activation.
AB  - BACKGROUND: Carboxylesterases (CEs) are ubiquitous enzymes responsible for the
      hydrolysis of numerous clinically useful drugs. As ester moieties are frequently
      included in molecules to improve their water solubility and bioavailability, de
      facto they become substrates for CEs. OBJECTIVE: In this review, we describe the
      properties of human CEs with regard to their ability to activate anticancer
      prodrugs and demonstrate how structure-based design can be used to modulate
      substrate specificity and to increase efficiency of hydrolysis. METHODS: A
      specific example using CPT-11 and a human liver CE is discussed. However, these
      techniques can be applied to other enzymes and their associated prodrugs.
      RESULTS: Structure-guided mutagenesis of CEs can be employed to alter substrate
      specificity and generate novel enzymes that are efficacious at anticancer prodrug
      activation.

PMID- 18721112
TI  - Human cytochromes P450 in the metabolism of drugs: new molecular models of enzyme
      substrate interactions.
AB  - The overall predictive ability of molecular modelling, as applied to the
      cytochrome P450 (CYP) system, is analysed in the light of current developments in
      a variety of techniques, including X-ray crystallography, molecular biology,
      enzyme kinetics, molecular mechanics and dynamics, in relation to its relevance
      to drug metabolism in humans. This review demonstrates that it is possible to
      generate realistic models for the major human CYPs, which metabolise xenobiotics
      that compare favourably with crystal structures, and thus may be used to derive
      substrate binding energies that agree closely with experimental K(m) values
      obtained from enzyme kinetics.

PMID- 18721113
TI  - The use of inductively coupled plasma mass spectrometry as a detector in drug
      metabolism studies.
AB  - BACKGROUND: The inherent properties of element selectivity combined with high
      sensitivity and structure independent response, make inductively coupled plasma
      mass spectrometry (ICP-MS) an interesting alternative detection technique in drug
      metabolism studies. OBJECTIVE: The application of online separation with ICP-MS
      detection in drug metabolism studies is reviewed with focus on the merits and
      demerits of this detection technique. The prerequisite for inclusion in this
      review is that the study involves a separation technique hyphenated online to the
      ICP-MS detection. RESULT/CONCLUSION: ICP-MS detection is found to be advantageous
      for analysis of all drug substances detectable by ICP-MS compared to
      radiochemical detection. Detectable drugs are limited to halogen-, sulfur-, metal
      and metalloid-containing compounds. The drawback of interference from endogenous
      compounds on quantitative mass balance estimations of non-metal drugs is
      addressed. The potential of determining the stoichiometry in metallo-drug
      biomolecule interactions is pointed out by presenting examples of simultaneous
      monitoring of metals in metallo-drugs and intrinsic ICP-MS detectable elements in
      biomolecules. It is concluded that ICP-MS detection is an indispensable technique
      in drug metabolism studies of metallo-drugs, although the applicability for
      traditional drugs is limited.

PMID- 18721114
TI  - Treatment of leishmaniasis with miltefosine: 2008 status.
AB  - BACKGROUND: Miltefosine is the first recognized oral treatment for leishmaniasis.
      It was first registered, in 2002, for Indian visceral leishmaniasis, and was
      reviewed by the present author in 2005. QUESTION: Miltefosine is now being used
      for the full range of clinical leishmaniasis. The present review addresses non
      clinical and clinical advances since 2005. METHODS: PubMed was accessed for all
      articles on miltefosine from 2005 to 2008. RESULTS/CONCLUSIONS: Miltefosine is
      effective and can be recommended for visceral disease in India and in Ethiopia,
      and for cutaneous disease in Colombia and Bolivia. For unusual forms of disease
      that require long periods of treatment such as diffuse cutaneous leishmaniasis
      and post-kala-azar dermal leishmaniasis, oral miltefosine is probably the
      treatment of choice.

PMID- 18721115
TI  - Pentostatin in chronic lymphocytic leukemia.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is a disease that typically
      afflicts older individuals with a median age of diagnosis in the eighth decade of
      life for which treatments available now are not curative. Although purine
      analogue based combinations produce complete responses (CRs) in many patients,
      the use of these combinations has been limited by toxicity including
      myelosuppression and an increased risk of infectious complications. OBJECTIVE: To
      identify the role of pentostatin, a specific inhibitor of adenosine deaminase
      (ADA), in the treatment of CLL. We compare pentostatin to other purine analogues,
      most notably fludarabine, with regard to safety and efficacy. Finally, we review
      the use of pentostatin in other diseases. METHODS: The scope of this review
      encompasses the history of treatment for CLL as well as the genesis of modern
      combination chemoimmunotherapy and the advantages of pentostatin within such a
      treatment program. RESULTS: Combination therapy with pentostatin seems to provide
      response frequencies comparable to fludarabine based combinations but with less
      toxicity and with greater ease of administration.

PMID- 18721117
TI  - Clinical development of metformin extended-release tablets for type 2 diabetes:
      an overview.
AB  - Glumetz (Depomed, Inc., Menlo Park, CA, USA) is a recently approved gastric
      retentive extended-release formulation of metformin (M-ER) that provides
      effective, sustained and well-tolerated glycemic control with once daily
      administration. Pharmacokinetic studies have demonstrated a similar
      bioavailability of M-ER administered once daily to immediate-release metformin
      given twice daily. In addition, M-ER has demonstrated a nearly linear dose
      proportionality with a relative bioavailability of highest dose to lowest dose of
      80%, whereas with immediate-release metformin the relative bioavailability of the
      highest dose to the lowest dose is only 58%. M-ER demonstrated a positive food
      effect and should be administered with a meal, preferably the evening meal.
      Because metformin is only eliminated through renal mechanisms, the use of M-ER,
      as is the case with other formulations, is contraindicated in patients with renal
      impairment. Administration of M-ER with sulfonylureas (SUs) had no effect on the
      pharmacokinetics of metformin. In controlled clinical trials M-ER demonstrated
      efficacy for 24 weeks as a monotherapy or in combination with SU. Additionally,
      glycemic control was maintained for an extra 24 weeks in an open-label
      monotherapy extension study of M-ER. M-ER was well tolerated in all studies.

PMID- 18721116
TI  - Riluzole in psychiatry: a systematic review of the literature.
AB  - BACKGROUND: The glutamate system seems to be an important contributor to the
      pathophysiology of mood and anxiety disorders. Thus, glutamatergic modulators are
      reasonable candidate drugs to test in patients with mood and anxiety disorders.
      Riluzole, a neuroprotective agent with anticonvulsant properties approved for the
      treatment of amyotrophic lateral sclerosis (ALS) is one such agent. OBJECTIVE: To
      assess the potential risks and benefits of riluzole treatment in psychiatric
      patients. METHODS: A PubMed search was performed using the keywords 'riluzole',
      'inhibitor of glutamate release' and 'glutamatergic modulator' to identify all
      clinical studies and case reports involving riluzole in psychiatric patients.
      RESULTS/CONCLUSION: Riluzole's side effect profile is favorable and preliminary
      results regarding riluzole for the treatment of severe mood, anxiety and
      impulsive disorders are encouraging.

PMID- 18721118
TI  - The importance of the new CONSORT Statement for clinicians.

PMID- 18721119
TI  - Most clinical tests cannot accurately diagnose rotator cuff pathology: a
      systematic review.
AB  - QUESTION: Do clinical tests accurately diagnose rotator cuff pathology? DESIGN: A
      systematic review of investigations into the diagnostic accuracy of clinical
      tests for rotator cuff pathology. PARTICIPANTS: People with shoulder pain who
      underwent clinical testing in order to diagnose rotator cuff pathology. OUTCOME
      MEASURES: The diagnostic accuracy of clinical tests was determined using
      likelihood ratios. RESULTS: Thirteen studies met the inclusion criteria. The 13
      studies evaluated 14 clinical tests in 89 separate evaluations of diagnostic
      accuracy. Only one evaluation, palpation for supraspinatus ruptures, resulted in
      significant positive and negative likelihood ratios. Eight of the 89 evaluations
      resulted in either significant positive or negative likelihood ratios. However,
      none of these eight positive or negative likelihood ratios were found in other
      studies. Of the 89 evaluations of clinical tests 71 (80%) did not result in
      either significant positive or negative likelihood ratio evaluations across
      different studies. CONCLUSION: Overall, most tests for rotator cuff pathology
      were inaccurate and cannot be recommended for clinical use. At best, suspicion of
      a rotator cuff tear may be heightened by a positive palpation, combined
      Hawkins/painful arc/infraspinatus test, Napoleon test, lift-off test, belly-press
      test, or drop-arm test, and it may be reduced by a negative palpation, empty can
      test or Hawkins-Kennedy test.

PMID- 18721120
TI  - Oxygenation and static compliance is improved immediately after early manual
      hyperinflation following myocardial revascularisation: a randomised controlled
      trial.
AB  - QUESTION: Are oxygenation and static compliance improved immediately after manual
      hyperinflation following myocardial revascularisation? Does this lead to earlier
      extubation and shorter hospital stay? Does it reduce postoperative pulmonary
      complications? DESIGN: Randomised controlled trial with concealed allocation,
      blinded assessment and intention-to-treat analysis. PARTICIPANTS: Fifty-five
      patients who underwent myocardial revascularisation. INTERVENTION: After an hour
      in recovery, the experimental group received manual hyperinflation with positive
      end expiratory pressure followed by suction while the control group received
      suction only. OUTCOME MEASURES: Oxygenation (PaO(2) in mmHg) and static lung
      compliance (in ml/cmH(2)O) were measured immediately after suction. Time to
      extubation (in minutes) and length of hospital stay (in days) were collected and
      postoperative pulmonary complications were confirmed by X-ray. RESULTS: PaO(2)
      was 11.7 mmHg (95% CI 9.4 to 14.0) greater in the experimental group while static
      compliance was 8.5 ml/cmH(2)0 (95% CI 6.4 to 10.6) greater than in the control
      group. The experimental group was extubated 76 minutes (95% CI 24 to 128) earlier
      than the control group but did not have a shorter length of stay (mean difference
      0.5 days, 95% CI -0.2 to 1.2). The relative risk of postoperative pulmonary
      complications was no greater (RR 0.57, 95% Cl 0.20 to 1.60) in the experimental
      group than in the control group. CONCLUSION: The group that received early manual
      hyperinflation had markedly better oxygenation and static compliance as well as
      shorter mechanical ventilation times than the control group. The length of
      hospital stay and incidence of postoperative pulmonary complications were similar
      in the two groups.

PMID- 18721121
TI  - A single session of Acu-TENS increases FEV1 and reduces dyspnoea in patients with
      chronic obstructive pulmonary disease: a randomised, placebo-controlled trial.
AB  - QUESTIONS: What is the immediate effect of a single 45-minute session of
      transcutaneous electrical nerve stimulation over acupoints (Acu-TENS) on lung
      function and dyspnoea in patients with chronic obstructive pulmonary disease?
      DESIGN: Randomised, placebo-controlled trial with concealed allocation,
      participant blinding, assessor blinding, and intention-to-treat analysis.
      PARTICIPANTS: Forty-six ambulatory patients with a mean age of 75 years, with
      stage I or II chronic obstructive pulmonary disease, and with no previous
      experience of TENS or acupuncture. INTERVENTION: The experimental group received
      45 minutes of Acu-TENS over acupoint Ex-B1 bilaterally (0.5 'cun' lateral to the
      spinous process of the 7(th) cervical vertebra) while the control group received
      placebo-TENS with identical electrode placement but no electrical output despite
      a flashing light indicating stimulus delivery. OUTCOME MEASURES: Lung function
      was measured as FEV1 and FVC while dyspnoea was measured using a shortness of
      breath 100-mm visual analogue scale. RESULTS: After 45 minutes of Acu-TENS, the
      experimental group had increased FEV1 by 0.12 litres (95% CI 0.07 to 0.15) and
      decreased dyspnoea by 10.7 mm (95% CI -13.9 to -7.6) more than the control group.
      The effect on FVC was only small (mean difference 0.05 litres, 95% CI -0.01 to
      0.10). CONCLUSION: Acu-TENS may be a useful non-invasive adjunctive intervention
      in the management of dyspnoea in patients with chronic obstructive pulmonary
      disease. This study suggests that the effect of long-term Acu-TENS warrants
      further investigation.

PMID- 18721122
TI  - Electrical simulation in addition to passive stretch has a small effect on
      spasticity and contracture in children with cerebral palsy: a randomised within
      participant controlled trial.
AB  - QUESTION: Does electrical stimulation in addition to passive stretching reduce
      spasticity and contracture more than passive stretching alone in children with
      cerebral palsy? DESIGN: Randomised within-participant controlled trial with
      concealed allocation, assessor blinding, and intention-to-treat analysis.
      PARTICIPANTS: Eleven (one dropout) children with cerebral palsy and bilateral
      knee flexor spasticity aged 13 years (SD 1). INTERVENTION: One leg in each
      participant received the experimental intervention for four weeks which consisted
      of 30 min of electrical stimulation of the quadriceps 3 times per week and
      passive stretching of the hamstrings 5 times per week. The other leg received the
      control intervention for four weeks which consisted of passive stretching of the
      hamstrings 5 times per week. OUTCOME MEASURES: Spasticity of the hamstrings was
      measured using the modified Ashworth scale. Contracture was measured as maximum
      passive knee extension using goniometry. RESULTS: The mean difference in decrease
      in the modified Ashworth score due to the addition of electrical stimulation to
      the stretching regimen was 0.8 points (95% CI 0.1 to 1.5). The mean difference in
      increase in passive knee extension due to the addition of electrical stimulation
      to the stretching regimen was 4 degrees (95% CI 0 to 7). CONCLUSION: Electrical
      stimulation combined with passive stretching is marginally more effective than
      passive stretching alone for spastic limbs of children with cerebral palsy.

PMID- 18721123
TI  - Perceived school bag load, duration of carriage, and method of transport to
      school are associated with spinal pain in adolescents: an observational study.
AB  - QUESTION: Are use and perceived load of school bags and the prevalence of spinal
      pain different between male and female adolescents? Is use of school bags related
      to perceived load of school bags? Are use and perceived load of school bags
      related to spinal pain? DESIGN: Cross-sectional observational study.
      PARTICIPANTS: 1202 adolescents recruited from the 'Raine' Cohort Study. OUTCOME
      MEASURES: Use and perceived load of school bags as well as spinal pain were
      measured by questionnaire. RESULTS: The prevalence of back and neck pain was
      approximately 50%; 53% of females reported neck pain compared with 44% of males
      (p < 0.01). Almost half of participants carried their school bag for more than 30
      minutes per day with 85% carrying their bag over both shoulders. School bags were
      felt to be heavy by 54% and to cause fatigue by 51%. Carrying a school bag for
      more than 30 minutes daily and taking an inactive form of transport to school
      (car or bus) increased the odds of having both back (OR 1.40, 95% CI 1.08 to
      1.82) and neck pain (OR 1.47, 95% CI 1.13 to 1.91). CONCLUSION: Neck pain is as
      common as back pain amongst adolescents. Perceived school bag load, duration of
      carriage and method of transport to school are associated with back and neck
      pain. Physical activity in the form of walking or riding to school may offset the
      potentially provocative effects of prolonged bag carriage and warrants further
      investigation.

PMID- 18721124
TI  - Cost and utilisation of healthcare resources during rehabilitation after ankle
      fracture are not linked to health insurance, income, gender, or pain: an
      observational study.
AB  - QUESTION: What are the costs and utilisation of healthcare resources, their
      determinants, and quality of life for people attending outpatient physiotherapy
      after ankle fracture? DESIGN: Longitudinal observational study. PARTICIPANTS:
      Ninety-four adults (2 dropouts) following cast removal after isolated ankle
      fracture attending outpatient physiotherapy at three hospitals in Sydney,
      Australia. OUTCOME MEASURES: Costs incurred (direct healthcare costs and out-of
      pocket costs) and utilisation of healthcare system resources were measured at 4,
      8, 12, 16, 20, and 24 weeks. Quality of life was measured shortly after cast
      removal and at 4, 12, and 24 weeks. Factors known to influence costs and
      utilisation in other conditions (private health insurance, income level, gender,
      and pain) were also measured. RESULTS: The total cost per person was AUD 735 (SD
      876) over 24 weeks. Outpatient physiotherapy accounted for the highest costs in
      both direct healthcare (39%) and out-of-pocket (42%) costs. Less than 20% of
      participants sought private non-medical care in addition to receiving outpatient
      physiotherapy. None of the factors investigated had a significant influence on
      costs and utilisation. Quality of life score improved over the 24 weeks by a mean
      of 6.1 points out of 45 (95% CI 5.2 to 6.9), with most of the improvement
      occurring in the domain of independent living. CONCLUSION: Information on costs
      and utilisation of healthcare resources can be used to plan health services, eg,
      the number of physiotherapy sessions required after ankle fracture. Private
      health insurance, income level, gender, or pain did not influence the costs or
      the decision behind seeking care over and above publicly-provided physiotherapy.

PMID- 18721126
TI  - Embedding research and researchers in clinical practice is fundamental.

PMID- 18721125
TI  - Physical activity by elderly patients undergoing inpatient rehabilitation is low:
      an observational study.
AB  - QUESTION: Are there differences in physical activity between older adults
      undergoing inpatient rehabilitation and those living in the community? Are there
      differences in physical activity within and between these two groups on weekdays
      compared to weekends? Are there differences in physical activity within and
      between these two groups over the day? DESIGN: An observational study.
      PARTICIPANTS: Twenty-five elderly patients (aged 81 years) undergoing
      rehabilitation and 25 age- and gender-matched community-dwelling people (aged 80
      years). OUTCOME MEASURES: The Positional Activity Logger was used to measure the
      frequency and duration of time spent upright (uptime), over three consecutive
      days, including a weekend day. RESULTS: The inpatient group achieved a median
      daily uptime of 1.3 hours which was significantly less than the community group's
      median of 5.5 hours (p < 0.001). Uptime for inpatients was significantly greater
      on weekdays (1.6 hours) when therapy was available than on weekend days (1.1
      hours) when therapy was generally not available (p < 0.001), whereas uptime for
      community participants was no different on weekdays (5.9 hours) than on weekend
      days (4.8 hours) (p = 0.05). Median uptime was significantly less for the
      inpatient group than for the community group at all times of day (p < 0.001).
      CONCLUSION: Elderly patients undergoing rehabilitation spend much of the day less
      physically active than their community peers.

PMID- 18721127
TI  - Genetically modified adenoviral vector with the protein transduction domain of
      Tat improves gene transfer to CAR-deficient cells.
AB  - The transduction efficiency of Ad (adenovirus) depends, to some extent, on the
      expression level of CAR (coxsackievirus and Ad receptor) of a target cell. The
      low level of CAR on the cell surface is a potential barrier to efficient gene
      transfer. To overcome this problem, PTD.AdeGFP (where eGFP is enhanced green
      fluorescent protein) was constructed by modifying the HI loop of Ad5 (Ad type 5)
      fibre with the Tat (trans-activating) PTD (protein transduction domain) derived
      from HIV. The present study showed that PTD.AdeGFP significantly improved gene
      transfer to multiple cell types deficient in expression of CAR. The improvement
      in gene transfer was not the result of charge-directed binding between the virus
      and the cell surface. Although PTD.AdeGFP formed aggregates, it infected target
      cells in a manner different from AdeGFP aggregates precipitated by calcium
      phosphate. In addition, PTD.AdeGFP was able to transduce target cells in a
      dynamin-independent pathway. The results provide some new clues as to how
      PTD.AdeGFP infects target cells. This new vector would be valuable in gene
      function analysis and for gene therapy in cancer.

PMID- 18721128
TI  - Salt-stress-induced association of phosphatidylinositol 4,5-bisphosphate with
      clathrin-coated vesicles in plants.
AB  - Plants exposed to hyperosmotic stress undergo changes in membrane dynamics and
      lipid composition to maintain cellular integrity and avoid membrane leakage.
      Various plant species respond to hyperosmotic stress with transient increases in
      PtdIns(4,5)P(2); however, the physiological role of such increases is unresolved.
      The plasma membrane represents the outermost barrier between the symplast of
      plant cells and its apoplastic surroundings. In the present study, the spatio
      temporal dynamics of stress-induced changes in phosphoinositides were analysed in
      subcellular fractions of Arabidopsis leaves to delineate possible physiological
      roles. Unlabelled lipids were separated by TLC and quantified by gas
      chromatographic detection of associated fatty acids. Transient PtdIns(4,5)P(2)
      increases upon exposure to hyperosmotic stress were detected first in enriched
      plasmamembrane fractions, however, at later time points, PtdIns(4,5)P(2) was
      increased in the endomembrane fractions of the corresponding two-phase systems.
      When major endomembranes were enriched from rosette leaves prior to hyperosmotic
      stress and during stimulation for 60 min, no stress-induced increases in the
      levels of PtdIns(4,5)P(2) were found in fractions enriched for endoplasmic
      reticulum, nuclei or plastidial membranes. Instead, increased PtdIns(4,5)P(2) was
      found in CCVs (clathrin-coated vesicles), which proliferated several-fold in mass
      within 60 min of hyperosmotic stress, according to the abundance of CCV
      associated proteins and lipids. Monitoring the subcellular distribution of
      fluorescence-tagged reporters for clathrin and PtdIns(4,5)P(2) during transient
      co-expression in onion epidermal cells indicates rapid stress-induced co
      localization of clathrin with PtdIns(4,5)P(2) at the plasma membrane. The results
      indicate that PtdIns(4,5)P(2) may act in stress-induced formation of CCVs in
      plant cells, highlighting the evolutionary conservation of the phosphoinositide
      system between organismic kingdoms.

PMID- 18721129
TI  - Novel haem co-ordination variants of flavocytochrome P450BM3.
AB  - Bacillus megaterium flavocytochrome P450 BM3 is a catalytically self-sufficient
      fatty acid hydroxylase formed by fusion of soluble NADPH-cytochrome P450
      reductase and P450 domains. Selected mutations at residue 264 in the haem (P450)
      domain of the enzyme lead to novel amino acid sixth (distal) co-ordination
      ligands to the haem iron. The catalytic, spectroscopic and thermodynamic
      properties of the A264M, A264Q and A264C variants were determined in both the
      intact flavocytochromes and haem domains of P450 BM3. Crystal structures of the
      mutant haem domains demonstrate axial ligation of P450 haem iron by methionine
      and glutamine ligands trans to the cysteine thiolate, creating novel haem iron
      ligand sets in the A264M/Q variants. In contrast, the crystal structure of the
      A264C variant reveals no direct interaction between the introduced cysteine side
      chain and the haem, although EPR data indicate Cys(264) interactions with haem
      iron in solution. The A264M haem potential is elevated by comparison with wild
      type haem domain, and substrate binding to the A264Q haem domain results in a
      approximately 360 mV increase in potential. All mutant haem domains occupy the
      conformation adopted by the substrate-bound form of wild-type BM3, despite the
      absence of added substrate. The A264M mutant (which has higher dodecanoate
      affinity than wild-type BM3) co-purifies with a structurally resolved lipid.
      These data demonstrate that a single mutation at Ala(264) is enough to perturb
      the conformational equilibrium between substrate-free and substrate-bound P450
      BM3, and provide firm structural and spectroscopic data for novel haem iron
      ligand sets unprecedented in nature.

PMID- 18721130
TI  - Increased tyrosine phosphorylation of PSD-95 by Src family kinases after brain
      ischaemia.
AB  - PSD (postsynaptic density)-95, a scaffold protein that tethers NMDA (N-methyl-D
      aspartate) receptors to signal molecules, is implicated in pathological events
      resulting from excitotoxicity. The present study demonstrates that brain
      ischaemia and reperfusion increase the tyrosine phosphorylation of PSD-95 in the
      rat hippocampus. PP2, a specific inhibitor of SrcPTKs (Src family protein
      tyrosine kinases), prevents the ischaemia-induced increases not only in the
      tyrosine phosphorylation of PSD-95, but also in the interaction between PSD-95
      and Src kinases. PSD-95 is phosphorylated either by purified Src/Fyn kinases in
      vitro or by co-expression of constitutively active Src/Fyn in COS7 cells. The
      results suggest that SrcPTKs are involved in PSD-95 phosphorylation. The single
      Tyr(523) mutation to phenylalanine (Y523F) reduces the Src/Fyn-mediated
      phosphorylation of PSD-95 in COS7 cells and in vitro. As shown with a rabbit
      polyclonal antibody against phospho-PSD-95 (Tyr(523)), Tyr(523) phosphorylation
      is responsible for the increased tyrosine phosphorylation of PSD-95 induced by
      ischaemia in the rat hippocampus. In cultured hippocampal neurons, overexpression
      of PSD-95 Y523F, but not PSD-95 Y533F, abolishes the facilitating effect of PSD
      95 on the glutamate- or NMDA-mediated currents, implying that PSD-95 Tyr(523)
      phosphorylation contributes to the post-ischaemic over-activation of NMDA
      receptors. Thus the present study reveals an additional mechanism for the
      regulation of PSD-95 by tyrosine phosphorylation. This mechanism may be of
      pathological significance since it is associated with excitotoxicity in the
      ischaemic brain.

PMID- 18721134
TI  - Direct CIII-HflB interaction is responsible for the inhibition of the HflB (FtsH)
      mediated proteolysis of Escherichia coli sigma(32) by lambdaCIII.
AB  - The CIII protein of bacteriophage lambda exhibits antiproteolytic activity
      against the ubiquitous metalloprotease HflB (FtsH) of Escherichia coli, thereby
      stabilizing the lambdaCII protein and promoting lysogenic development of the
      phage. CIII also protects E.coli sigma(32), another substrate of HflB. We have
      recently shown that the protection of CII from HflB by CIII involves direct CIII
      HflB binding, without any interaction between CII and CIII [HalderS, DattaAB &
      Parrack P (2007) J Bacteriol189, 8130-8138]. Such a mode of action for lambdaCIII
      would be independent of the HflB substrate. In this study, we tested the ability
      of CIII to protect sigma(32) from HflB digestion. The inhibition of HflB-mediated
      proteolysis of sigma(32) by CIII is very similar to that of lambdaCII,
      characterized by an enhanced protection by the core CIII peptide CIIIC (amino
      acids 14-41 of lambdaCIII) and a lack of interaction between sigma(32) and CIII.

PMID- 18721135
TI  - Increased glucose metabolism and ATP level in brain tissue of Huntington's
      disease transgenic mice.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder
      characterized by multifarious dysfunctional alterations including mitochondrial
      impairment. In the present study, the formation of inclusions caused by the
      mutation of huntingtin protein and its relationship with changes in energy
      metabolism and with pathological alterations were investigated both in transgenic
      and 3-nitropropionic acid-treated mouse models for HD. The HD and normal mice
      were characterized clinically; the affected brain regions were identified by
      immunohistochemistry and used for biochemical analysis of the ATP-producing
      systems in the cytosolic and the mitochondrial compartments. In both HD models,
      the activities of some glycolytic enzymes were somewhat higher. By contrast, the
      activity of glyceraldehyde-3-phosphate dehydrogenase was much lower in the
      affected region of the brain compared to that of the control. Paradoxically, at
      the system level, glucose conversion into lactate was enhanced in cytosolic
      extracts from the HD brain tissue, and the level of ATP was higher in the tissue
      itself. The paradox could be resolved by taking all the observed changes in
      glycolytic enzymes into account, ensuing an experiment-based detailed
      mathematical model of the glycolytic pathway. The mathematical modelling using
      the experimentally determined kinetic parameters of the individual enzymes and
      the well-established rate equations predicted the measured flux and
      concentrations in the case of the control. The same mathematical model with the
      experimentally determined altered V(max) values of the enzymes did account for an
      increase of glycolytic flux in the HD sample, although the extent of the increase
      was not predicted quantitatively. This suggested a somewhat altered regulation of
      this major metabolic pathway in HD tissue. We then used the mathematical model to
      develop a hypothesis for a new regulatory interaction that might account for the
      observed changes; in HD, glyceraldehyde-3-phosphate dehydrogenase may be in
      closer proximity (perhaps because of the binding of glyceraldehyde-3-phosphate
      dehydrogenase to huntingtin) with aldolase and engage in channelling for
      glyceraldehyde-3-phosphate. By contrast to most of the speculation in the
      literature, our results suggest that the neuronal damage in HD tissue may be
      associated with increased energy metabolism at the tissue level leading to
      modified levels of various intermediary metabolites with pathological
      consequences.

PMID- 18721136
TI  - Characterization of mutations in crucial residues around the Q(o) binding site of
      the cytochrome bc complex from Paracoccus denitrificans.
AB  - The protonation state of residues around the Q(o) binding site of the cytochrome
      bc(1) complex from Paracoccus denitrificans and their interaction with bound
      quinone(s) was studied by a combined electrochemical and FTIR difference
      spectroscopic approach. Site-directed mutations of two groups of conserved
      residues were investigated: (a) acidic side chains located close to the surface
      and thought to participate in a water chain leading up to the heme b(L) edge, and
      (b) residues located in the vicinity of this site. Interestingly, most of the
      mutants retain a high degree of catalytic activity. E295Q, E81Q and Y297F showed
      reduced stigmatellin affinity. On the basis of electrochemically induced FTIR
      difference spectra, we suggest that E295 and D278 are protonated in the oxidized
      form or that their mutation perturbs protonated residues. Mutations Y302, Y297,
      E81 and E295, directly perturb signals from the oxidized quinone and of the
      protein backbone. By monitoring the interaction with the inhibitor stigmatellin
      for the wild-type enzyme at various redox states, interactions of the bound
      stigmatellin with amino acid side chains such as protonated acidic residues and
      the backbone were observed, as well as difference signals arising from the redox
      active inhibitor itself and the replaced quinone. The infrared difference spectra
      of the above Q(o) site mutations in the presence of stigmatellin confirm the
      previously established role of E295 as a direct interaction partner in the enzyme
      from P.denitrificans as well. The protonated residue E295 is proposed to change
      the hydrogen-bonding environment upon stigmatellin binding in the oxidized form,
      and is deprotonated in the reduced form. Of the residues located close to the
      surface, D278 remains protonated and unperturbed in the oxidized form but its
      frequency shifts in the reduced form. The mechanistic implications of our
      observations are discussed, together with previous inhibitor binding data, and
      referred to the published X-ray structures.

PMID- 18721137
TI  - Interactions between the Fyn SH3-domain and adaptor protein Cbp/PAG derived
      ligands, effects on kinase activity and affinity.
AB  - Csk-binding protein/phosphoprotein associated with glycosphingolipid-enriched
      domains is a transmembrane adaptor protein primarily involved in negative
      regulation of T-cell activation by recruitment of C-terminal Src kinase (Csk), a
      protein tyrosine kinase which represses Src kinase activity through C-terminal
      phosphorylation. Recruitment of Csk occurs via SH2-domain binding to PAG pTyr317,
      thus, the interaction is highly dependent on phosphorylation performed by the Src
      family kinase Fyn, which docks onto PAG using a dual-domain binding mode
      involving both SH3- and SH2-domains of Fyn. In this study, we investigated Fyn
      SH3-domain binding to 14-mer peptide ligands derived from Cbp/PAG-enriched
      microdomains sequence using biochemical, biophysical and computational
      techniques. Interaction kinetics and dissociation constants for the various
      ligands were determined by SPR. The local structural impact of ligand association
      has been evaluated using CD, and molecular modelling has been employed to
      investigate details of the interactions. We show that data from these
      investigations correlate with functional effects of ligand binding, assessed
      experimentally by kinase assays using full-length PAG proteins as substrates. The
      presented data demonstrate a potential method for modulation of Src family kinase
      tyrosine phosphorylation through minor changes of the substrate SH3-interacting
      motif.

PMID- 18721138
TI  - Probing the rotor subunit interface of the ATP synthase from Ilyobacter
      tartaricus.
AB  - The interaction between the c(11)ring and the gammaepsilon complex, forming the
      rotor of the Ilyobacter tartaricus ATP synthase, was probed by surface plasmon
      resonance spectroscopy and in vitro reconstitution analysis. The results provide,
      for the first time, a direct and quantitative assessment of the stability of the
      rotor. The data indicated very tight binding between the c(11)ring and the
      gammaepsilon complex, with an apparent K(d) value of approximately 7.4nm. The
      rotor assembly was primarily dependent on the interaction of the cring with the
      gammasubunit, and binding of the cring to the free epsilon subunit was not
      observed. Mutagenesis of selected conserved amino acid residues of all three
      rotor components (cR45, cQ46, gammaE204, gammaF203 and epsilonH38) severely
      affected rotor assembly. The interaction kinetics between the gammaepsilon
      complex and c(11)ring mutants suggested that the assembly of the
      c(11)gammaepsiloncomplex was governed by interactions of low and high affinity.
      Low-affinity binding was observed between the polar loops of the cring subunits
      and the bottom part of the gamma subunit. High-affinity interactions, involving
      the two residues gammaE204 and epsilonH38, stabilized the holo-c(11)gammaepsilon
      complex. NMR experiments indicated the acquisition of conformational order in
      otherwise flexible C- and N-terminal regions of the gamma subunit on rotor
      assembly. The results of this study suggest that docking of the central stalk of
      the F(1)complex to the rotor ring of F(o) to form tight, but reversible, contacts
      provides an explanation for the relative ease of dissociation and reconstitution
      of F(1)F(o)complexes.

PMID- 18721139
TI  - Effect of the disease-causing mutations identified in human ribonuclease (RNase)
      H2 on the activities and stabilities of yeast RNase H2 and archaeal RNase HII.
AB  - Eukaryotic ribonuclease (RNase) H2 consists of one catalytic and two accessory
      subunits. Several single mutations in any one of these subunits of human RNase H2
      cause Aicardi-Goutieres syndrome. To examine whether these mutations affect the
      complex stability and activity of RNase H2, three mutant proteins of His-tagged
      Saccharomyces cerevisiae RNase H2 (Sc-RNase H2*) were constructed. Sc-G42S*, Sc
      L52R*, and Sc-K46W* contain single mutations in Sc-Rnh2Ap*, Sc-Rnh2Bp*, and Sc
      Rnh2Cp*, respectively. The genes encoding the three subunits were coexpressed in
      Escherichia coli, and Sc-RNase H2* and its derivatives were purified in a
      heterotrimeric form. All of these mutant proteins exhibited enzymatic activity.
      However, only the enzymatic activity of Sc-G42S* was greatly reduced compared to
      that of the wild-type protein. Gly42 is conserved as Gly10 in Thermococcus
      kodakareansis RNase HII. To analyze the role of this residue, four mutant
      proteins, Tk-G10S, Tk-G10A, Tk-G10L, and Tk-G10P, were constructed. All mutant
      proteins were less stable than the wild-type protein by 2.9-7.6 degrees C in
      T(m). A comparison of their enzymatic activities, substrate binding affinities,
      and CD spectra suggests that the introduction of a bulky side chain into this
      position induces a local conformational change, which is unfavorable for both
      activity and substrate binding. These results indicate that Gly10 is required to
      make the protein fully active and stable.

PMID- 18721140
TI  - Matrilysin (matrix metalloprotease-7) cleaves membrane-bound annexin II and
      enhances binding of tissue-type plasminogen activator to cancer cell surfaces.
AB  - Matrilysin (matrix metalloproteinase-7) plays important roles in tumor
      progression. It was previously found that matrilysin binds to the surface of
      colon cancer cells to promote their metastatic potential. In this study, we
      identified annexin II as a novel membrane-bound substrate of matrilysin.
      Treatment of human colon cancer cell lines with active matrilysin released a 35 k
      Da annexin II form, which lacked its N-terminal region, into the culture
      supernatant. The release of the 35 k Da annexin II by matrilysin was
      significantly enhanced in the presence of serotonin or heparin. Matrilysin
      hydrolyzed annexin II at the Lys9-Leu10 bond, thus dividing the protein into an N
      terminal nonapeptide and the C-terminal 35 k Da fragment. Annexin II is known to
      serve as a cell surface receptor for tissue-type plasminogen activator (tPA).
      Although the matrilysin treatment liberated the 35 k Da fragment of annexin II
      from the cell surface, it significantly increased tPA binding to the cell
      membrane. A synthetic N-terminal nonapeptide of annexin II bound to tPA more
      efficiently than intact annexin II. This peptide formed a heterodimer with intact
      annexin II in test tubes and on cancer cell surfaces. These and other results
      suggested that the nonapeptide generated by matrilysin treatment might be
      anchored to the cell membrane, possibly by binding to intact annexin II, and
      interact with tPA via its C-terminal lysine. It is supposed that the cleavage of
      cell surface annexin II by matrilysin contributes to tumor invasion and
      metastasis by enhancing tPA-mediated pericellular proteolysis by cancer cells.

PMID- 18721141
TI  - Deciphering the key residues in Plasmodium falciparum beta-ketoacyl acyl carrier
      protein reductase responsible for interactions with Plasmodium falciparum acyl
      carrier protein.
AB  - The type II fatty acid synthase (FAS) pathway of Plasmodium falciparum is a
      validated unique target for developing novel antimalarials, due to its intrinsic
      differences from the typeI pathway operating in humans. beta-Ketoacyl acyl
      carrier protein (ACP) reductase (FabG) performs the NADPH-dependent reduction of
      beta-ketoacyl-ACP to beta-hydroxyacyl-ACP, the first reductive step in the
      elongation cycle of fatty acid biosynthesis. In this article, we report intensive
      studies on the direct interactions of Plasmodium FabG and Plasmodium ACP in
      solution, in the presence and absence of its cofactor, NADPH, by monitoring the
      change in intrinsic fluorescence of P.falciparum FabG (PfFabG) and by surface
      plasmon resonance. To address the issue of the importance of the residues
      involved in strong, specific and stoichiometric binding of PfFabG to P.falciparum
      ACP (PfACP), we mutated Arg187, Arg190 and Arg230 of PfFabG. The activities of
      the mutants were assessed using both an ACP-dependent and an ACP-independent
      assay. The affinities of all the PfFabG mutants for acetoacetyl-ACP (the
      physiological substrate) were reduced to different extents as compared to wild
      type PfFabG, but were equally active in biochemical assays with the substrate
      analog acetoacetyl-CoA. Kinetic analysis and studies of direct binding between
      PfFabG and PfACP confirmed the identification of Arg187 and Arg230 as critical
      residues for the PfFabG-PfACP interactions. Our studies thus reveal the
      significance of the positively charged/hydrophobic patch located adjacent to the
      active site cavities of PfFabG for interactions with PfACP.

PMID- 18721142
TI  - Denitrifying bacteria anaerobically oxidize methane in the absence of Archaea.
AB  - Recently, a microbial consortium was shown to couple the anaerobic oxidation of
      methane to denitrification, predominantly in the form of nitrite reduction to
      dinitrogen gas. This consortium was dominated by bacteria of an as yet
      uncharacterized division and archaea of the order Methanosarcinales. The present
      manuscript reports on the upscaling of the enrichment culture, and addresses the
      role of the archaea in methane oxidation. The key gene of methanotrophic and
      methanogenic archaea, mcrA, was sequenced. The associated cofactor F(430) was
      shown to have a mass of 905 Da, the same as for methanogens and different from
      the heavier form (951 Da) found in methanotrophic archaea. After prolonged
      enrichment (> 1 year), no inhibition of anaerobic methane oxidation was observed
      in the presence of 20 mM bromoethane sulfonate, a specific inhibitor of MCR.
      Optimization of the cultivation conditions led to higher rates of methane
      oxidation and to the decline of the archaeal population, as shown by fluorescence
      in situ hybridization and quantitative MALDI-TOF analysis of F(430). Mass
      balancing showed that methane oxidation was still coupled to nitrite reduction in
      the total absence of oxygen. Together, our results show that bacteria can couple
      the anaerobic oxidation of methane to denitrification without the involvement of
      Archaea.

PMID- 18721143
TI  - AAN-EFNS guidelines on trigeminal neuralgia management.
AB  - Several issues regarding diagnosis, pharmacological treatment, and surgical
      treatment of trigeminal neuralgia (TN) are still unsettled. The American Academy
      of Neurology and the European Federation of Neurological Societies launched a
      joint Task Force to prepare general guidelines for the management of this
      condition. After systematic review of the literature the Task Force came to a
      series of evidence-based recommendations. In patients with TN MRI may be
      considered to identify patients with structural causes. The presence of
      trigeminal sensory deficits, bilateral involvement, and abnormal trigeminal
      reflexes should be considered useful to disclose symptomatic TN, whereas younger
      age of onset, involvement of the first division, unresponsiveness to treatment
      and abnormal trigeminal evoked potentials are not useful in distinguishing
      symptomatic from classic TN. Carbamazepine (stronger evidence) or oxcarbazepine
      (better tolerability) should be offered as first-line treatment for pain control.
      For patients with TN refractory to medical therapy early surgical therapy may be
      considered. Gasserian ganglion percutaneous techniques, gamma knife and
      microvascular decompression may be considered. Microvascular decompression may be
      considered over other surgical techniques to provide the longest duration of pain
      freedom. The role of surgery versus pharmacotherapy in the management of TN in
      patients with multiple sclerosis remains uncertain.

PMID- 18721145
TI  - Anaerobic degradation of long-chain alkylamines by a denitrifying Pseudomonas
      stutzeri.
AB  - The anaerobic degradation of tetradecylamine and other long-chain alkylamines by
      a newly isolated denitrifying bacterium was studied. Strain ZN6 was isolated from
      a mixture of soil and active sludge and was identified as representing
      Pseudomonas stutzeri, based on partial 16S rRNA gene sequence analysis. Strain
      ZN6 was a mesophilic, motile, Gram-negative rod-shaped bacterium and was able to
      grow on a variety of compounds including even-numbered primary fatty amines with
      alkyl chains ranging from C(4) to C(18) coupled to nitrate reduction. Alkylamines
      were used as sole carbon, energy and nitrogen source and were completely
      mineralized. Nitrate was dissimilated by ZN6 to nitrite. When strain ZN6 was
      grown under nitrate limitation, nitrite was slowly dissimilated further. When
      cocultivated with the complete denitrifier Castellaniella defragens ZN3,
      anaerobic degradation under denitrifying of alkylamines by strain ZN6 was
      slightly faster. Strain ZN3 is a complete denitrifier, unable to convert
      tetradecylamine, and was copurified from the same enrichment culture as strain
      ZN6. The proposed pathway for the degradation of alkylamines in strain ZN6 starts
      with C-N cleavages to alkanals and further oxidation to the corresponding fatty
      acids.

PMID- 18721144
TI  - Comparative analysis of ammonia monooxygenase (amoA) genes in the water column
      and sediment-water interface of two lakes and the Baltic Sea.
AB  - The functional gene amoA was used to compare the diversity of ammonia-oxidizing
      bacteria (AOB) in the water column and sediment-water interface of the two
      freshwater lakes Plusssee and Schohsee and the Baltic Sea. Nested amplifications
      were used to increase the sensitivity of amoA detection, and to amplify a 789-bp
      fragment from which clone libraries were prepared. The larger part of the
      sequences was only distantly related to any of the cultured AOB and is considered
      to represent new clusters of AOB within the Nitrosomonas/Nitrosospira group.
      Almost all sequences from the water column of the Baltic Sea and from 1-m depth
      of Schohsee were related to different Nitrosospira clusters 0 and 2,
      respectively. The majority of sequences from Plusssee and Schohsee were
      associated with sequences from Chesapeake Bay, from a previous study of Plusssee
      and from rice roots in Nitrosospira-like cluster A, which lacks sequences from
      Baltic Sea. Two groups of sequences from Baltic Sea sediment were related to
      clonal sequences from other brackish/marine habitats in the purely environmental
      Nitrosospira-like cluster B and the Nitrosomonas-like cluster. This confirms
      previous results from 16S rRNA gene libraries that indicated the existence of
      hitherto uncultivated AOB in lake and Baltic Sea samples, and showed a
      differential distribution of AOB along the water column and sediment of these
      environments.

PMID- 18721146
TI  - Bacterial quorum sensing and nitrogen cycling in rhizosphere soil.
AB  - Plant photosynthate fuels carbon-limited microbial growth and activity, resulting
      in increased rhizosphere nitrogen (N) mineralization. Most soil organic nitrogen
      is macromolecular (chitin, protein, nucleotides); enzymatic depolymerization is
      likely rate limiting for plant nitrogen accumulation. Analyzing Avena (wild oat)
      planted in microcosms containing sieved field soil, we observed increased
      rhizosphere chitinase and protease-specific activities, bacterial cell densities,
      and dissolved organic nitrogen (DON) compared with bulk soil. Low-molecular
      weight (MW) DON (<3000 Da) was undetectable in bulk soil but comprised 15% of
      rhizosphere DON. Extracellular enzyme production in many bacteria requires quorum
      sensing (QS), cell-density-dependent group behavior. Because proteobacteria are
      considered major rhizosphere colonizers, we assayed the proteobacterial QS
      signals N-acyl-homoserine lactones (AHLs), which were significantly increased in
      the rhizosphere. To investigate the linkage between soil signaling and nitrogen
      cycling, we characterized 533 bacterial isolates from Avena rhizosphere: 24% had
      chitinase or protease activity and AHL production; disruption of QS in seven of
      eight isolates disrupted enzyme activity. Many Alphaproteobacteria were newly
      found with QS-controlled extracellular enzyme activity. Enhanced specific
      activities of nitrogen-cycling enzymes accompanied by bacterial density-dependent
      behaviors in rhizosphere soil gives rise to the hypothesis that QS could be a
      control point in the complex process of rhizosphere nitrogen mineralization.

PMID- 18721147
TI  - Cloning of prokaryotic genes by a universal degenerate primer PCR.
AB  - A PCR approach was developed using a hexameric degenerate primer, which reflects
      the Shine-Dalgarno sequence of prokaryotic transcripts, hitherto named SD-PCR. In
      standard PCR reactions, the sizes and melting temperatures of the two primers are
      usually designed to be as equal as possible, while SD-PCR uses a single long gene
      specific primer pairing with a much-shorter universal degenerate primer. This
      approach can be used in PCR walking to clone either the upstream or the
      downstream region of a known sequence. We have successfully applied the method to
      template DNAs of different GC contents as well as complex mixtures composed of
      highly contaminating DNA(s).

PMID- 18721148
TI  - The phage K lytic enzyme LysK and lysostaphin act synergistically to kill MRSA.
AB  - LysK is the endolysin from the staphylococcal bacteriophage K, and can digest the
      cell wall of many staphylococci. Lysostaphin is a bacteriocin secreted by
      Staphylococcus simulans to kill Staphylococcus aureus. Both LysK and lysostaphin
      have been shown to lyse methicillin-resistant S. aureus (MRSA). This study
      describes optimal reaction conditions for the recombinant His-tagged LysK protein
      (pH range pH 6-10, and 0.3-0.5 M NaCl), and C-His-LysK MIC (32.85+/-4.87 mug mL(
      1)). LysK and lysostaphin demonstrate antimicrobial synergy by the checkerboard
      assay.

PMID- 18721149
TI  - Characterization of the quaternary amine transporters of Rhizobium leguminosarum
      bv. viciae 3841.
AB  - Rhizobium leguminosarum bv. viciae 3841 contains six putative quaternary ammonium
      transporters (Qat), of the ABC family. Qat6 was strongly induced by hyperosmosis
      although the solute transported was not identified. All six systems were induced
      by the quaternary amines choline and glycine betaine. It was confirmed by
      microarray analysis of the genome that pRL100079-83 (qat6) is the most strongly
      upregulated transport system under osmotic stress, although other transporters
      and 104 genes are more than threefold upregulated. A range of quaternary ammonium
      compounds were tested but all failed to improve growth of strain 3841 under
      hyperosmotic stress. One Qat system (gbcXWV) was induced 20-fold by glycine
      betaine and choline and a Tn5::gbcW mutant was severely impaired for both
      transport and growth on these compounds, demonstrating that it is the principal
      system for their use as carbon and nitrogen sources. It transports glycine
      betaine and choline with a high affinity (apparent K(m), 168 and 294 nM,
      respectively).

PMID- 18721150
TI  - Variability in bleeding phenotype in Amish carriers of haemophilia B with the
      31008 C-->T mutation.
AB  - The aim of this study was to characterize the variability of bleeding phenotype
      and its association with plasma factor IX coagulant activity (FIX:C) in
      haemophilia B carriers in a large Amish pedigree with a unifying genetic
      mutation, C-to-T transition at base 31008 of the factor IX gene (Xq27.1-27.2). A
      cross-sectional survey of haemophilia B carriers included a multiple choice
      questionnaire evaluating symptoms of mucocutaneous bleeding, joint bleeding and
      bleeding after haemostatic stress [menstruation, postpartum haemorrhage (PPH),
      dental extractions and invasive surgeries]. Severity of bleeding was graded as 0
      to 4, 0 being no bleeding whereas 4 being severe bleeding. Association between
      total bleeding scores and the FIX:C was evaluated. Sixty-four haemophilia B
      carriers participated in this study. Median age: 18 years (range 1-70 years);
      median bleeding score: 1 (range 0-8). Besides PPH, isolated symptoms of bruising,
      epistaxis, menorrhagia and postsurgical bleeding including dental extraction were
      not associated with lower FIX:C. Bleeding score >/=3 was associated with
      involvement of at least two bleeding sites and a lower mean FIX:C of 42 +/- 10.3%
      (95% CI 36.4-47.7) while a score >3 had involvement of </=2 sites and higher mean
      FIX:C of 54.9 +/- 21.5% (95% CI 49-61), P = 0.005. Subcutaneous haematoma
      formation and bleeding after haemostatic stress requiring treatment were
      associated with bleeding scores >/=3. Phenotypic variability existed among the
      carriers of haemophilia B who belonged to a single pedigree carrying a single
      unifying mutation. The utility of bleeding scores to define bleeding phenotype
      precisely in haemophilia B carriers needs further evaluation.

PMID- 18721151
TI  - Exercise and sport in the treatment of haemophilic patients: a systematic review.
AB  - In haemophiliacs, the physical condition, muscular strength, aerobic resistance,
      anaerobic resistance and proprioception have all diminished. Muscle atrophy and
      instability, being more vulnerable to stressful motor demands, increase the risk
      of lesion and establish a vicious circle that is hard to break: pain, immobility,
      atrophy, articular instability and repeated bleeding episodes. In haemophilia,
      physical and/or sporting activities were not recommended until the seventies.
      Nowadays, the overall policy is to recommend certain physical activities,
      especially swimming, to improve the patient's quality of life, thanks to
      prophylaxis programmes. The objective of this study is to perform a systematic
      review of the exercise and sporting activities recommended for haemophiliacs.
      Experimental and observational studies and clinical assays about rehabilitation
      for haemophiliacs with exercise and sporting activities have been included. The
      relevant studies were identified in Medline, Cinahl, Embase and SportDiscus, and
      key words were: haemophilia, exercise and sport (with no language restrictions).
      Works were independently analysed by reviewers and the following were identified:
      of 3603 studies, 103 were included in this review: 29 (28.15%) were experimental,
      27 (26.21%) were observational and 47 (45.63%) were clinical. Physiotherapy,
      physical activity and sport are basic elements to improve quality of life and the
      physical condition, increase strength and resistance and to reduce the risk of
      musculoskeletal lesions and to prevent haemophilic atrophy. In general,
      professionals in haemophilia believe that regular exercise and rehabilitation
      with physiotherapy is fundamental, particularly in countries where replacement
      therapy is not readily available.

PMID- 18721152
TI  - Uterine artery embolization: an approach to achieve haemostasis in post
      hysterectomy haemorrhages.

PMID- 18721153
TI  - Pathological role of CD44 on NKT cells in carbon tetrachloride-mediated liver
      injury.
AB  - AIM: CD44 has a variety of functions in immune regulation and signal
      transduction. Although CD44 is involved in the induction of several inflammatory
      diseases, it remains unknown whether CD44-targeting therapies are useful for
      liver diseases. Here, we examined whether CD44 blockade is effective in a
      chemical-induced liver injury model. METHODS: We injected CD44 knock out (KO) or
      wild type mice with carbon tetrachloride (CCl(4)) and examined the difference of
      liver injury by immunological or histological analysis. RESULTS: Although CD44KO
      mice exhibited suppressed liver injury at 6 h after CCl(4) injection with
      decreased inflammatory cell numbers and cytokine production, these mice showed
      severe liver injury at 24 h. We found that NKT cells played an important role in
      liver injury with increased infiltration of theliver after migration, which was
      independent of the CD44 pathway. In CD44NKT double-KO mice, liver injury was
      suppressed with reduced cytokine production and macrophage infiltration compared
      with CD44KO mice. Furthermore, MIP-2 derived from NKT cells or tumor necrosis
      factor alpha from macrophages contributed to exacerbation of the liver injury,
      since neutralization of MIP-2 provided significant protection against liver
      injury in CD44KO mice. Finally, we found that CD44KO mice exhibited excessive
      liver fibrosis compared with wild-type mice after repeated CCl(4) injections.
      CONCLUSION: We found that CD44 has unique characteristics for inflammatory liver
      diseases associated with NKT cell infiltration and activation. Furthermore, CD44
      targeting therapies may need to be viewed with caution for liver diseases due to
      the actions of the liver immune system.

PMID- 18721154
TI  - Prophylactic administration of antibiotics unnecessary following ultrasound
      guided biopsy and ablation therapy for liver tumors: Open-labeled randomized
      prospective study.
AB  - AIM: To determine the prophylactic effect of antibiotics administration in the
      prevention of infection following an ultrasound-guided percutaneous liver biopsy
      or treatment of liver tumors, we performed an open-labeled randomized prospective
      study of patients who received prophylactic antibiotics after undergoing those
      procedures. METHODS: We studied 101 patients, with ultrasound-guided percutaneous
      aspiration biopsies of the liver performed in 48 to diagnose diffuse liver
      diseases or liver tumors, while percutaneous ethanol-injection therapy was
      performed in two patients with malignant liver tumors and percutaneous
      radiofrequency ablation was performed in 51 patients. An oral administration of
      levofloxacin at 400 mg/day was given to 50 of the enrolled patients from the
      morning of the treatment day for three days. Preventive antibiotics were not
      administered to the remaining 51 patients. Body temperature, peripheral blood
      leukocyte number, c-reactive protein, alanine aminotransferase, and lactic
      dehydrogenase were measured daily for three days after treatment. RESULTS: Most
      parameters changed following percutaneous treatments of liver tumors, though no
      significant differences were seen between the patients treated with antibiotics
      and those untreated. Most significantly, there was no difference in the frequency
      of post-procedure infection between the groups. CONCLUSION: Our results suggest
      that prophylactic administration of antibiotics following a percutaneous liver
      biopsy and treatment of liver tumors does not have a significant impact on the
      post-procedure results or incidence of infection.

PMID- 18721155
TI  - Effect of ursodeoxycholic acid on serum liver enzymes and bile acid metabolism in
      chronic active hepatitis C virus infection.
AB  - AIM: Many reports have revealed ursodeoxycholic acid (UDCA) to be effective
      against chronic hepatitis C virus (HCV). However, some cases resist this therapy
      and the mechanism of action remains unclear. In this study, UDCA was administered
      to patients with chronic HCV and the correlation between the bile acids of the
      biliary bile and serum and the drug efficacy was investigated. METHODS: Fifteen
      patients were given 600 mg/day of UDCA for more than 24 weeks. The serum bile
      acid concentrations and biliary and serum bile acid were collected before and
      after 24 weeks of UDCA treatment, and composition determined by high-performance
      liquid chromatography. RESULTS: The treatment was effective in nine cases (ALT
      decreased to less than twice the normal values 80 IU/L) and ineffective in six
      cases. There was no significant difference in the serum bile acid concentrations
      before and after UDCA treatment between the values of both cases. After UDCA
      treatment, the serum percentage of UDCA (effective, 62.5 +/- 2.0; ineffective,
      53.5 +/- 2.5, (P = 0.02)) and the percentage of chenodeoxycholic acid (CDCA)
      showed no remarkable changes. In the biliary bile the percentage of CDCA
      (effective, 30.9 +/- 2.0; ineffective, 20.0 +/- 3.0, (P = 0.007)) and the
      percentage of UDCA showed no remarkable changes. CONCLUSION: In the effective
      cases, the percentage of UDCA in the serum and the percentage of CDCA in biliary
      bile were significantly higher than in the ineffective cases. This indicates
      that, when effective, CDCA decreases in hepatocytes and this reduction
      contributes to hepatoprotection.

PMID- 18721156
TI  - Reading, writing and systematic review.
AB  - AIM: This paper offers a discussion of the reading and writing practices that
      define systematic review. BACKGROUND: Although increasingly popular, systematic
      review has engendered a critique of the claims made for it as a more objective
      method for summing up research findings than other kinds of reviews. DISCUSSION:
      An alternative understanding of systematic review is as a highly subjective,
      albeit disciplined, engagement between resisting readers and resistant texts.
      Reviewers of research exemplify the resisting reader when they exclude reports on
      grounds of relevance, quality, or methodological difference. Research reports
      exemplify resistant texts as they do not simply yield their findings, but rather
      must be made docile to review. These acts of resistance make systematic review
      possible, but challenge claims of its greater capacity to control bias.
      CONCLUSION: An understanding of the reading and writing practices that define
      systematic review still holds truth and objectivity as regulative ideals, but is
      aware of the reading and writing practices that both enable and challenge those
      ideals.

PMID- 18721157
TI  - Explicating Benner's concept of expert practice: intuition in emergency nursing.
AB  - AIM: This paper is a report of a study exploring the experience of intuition in
      emergency nursing in relation to Benner's fifth stage of practice development,
      'the expert practitioner.' BACKGROUND: Expert nurses anecdotally report actions
      and thoughts that present in their consciousness and have an impact on the care
      given. Benner used the term 'intuition' for the fifth stage of practice
      development. However, Paley has criticized Benner's model for its lack of clarity
      about the nature of an expert practitioner. This criticism is further justified
      by Benner's inadequate explanation of expert. METHOD: A hermeneutic
      phenomenological study was conducted using van Manen's approach and a Gadamerian
      analysis. Fourteen expert emergency nurses in Australia were interviewed between
      January 2000 and December 2003. FINDINGS: The analysis resulted in the
      reconstruction of Benner's expert stage into three distinct phases: cognitive
      intuition, where assessment is processed subconsciously and can be rationalized
      in hindsight; transitional intuition, where a physical sensation and other
      behaviours enter the nurse's awareness; and embodied intuition, when the nurse
      trusts the intuitive thoughts. CONCLUSION: The findings validate the use of
      intuitive decision-making as a construct in explaining expert clinical decision
      making practices. The validity of intuitive practice should be recognized. It is
      essential to recognize the conditions that support practice development, and in
      the prenovice stage (during their university course) factors such as reflection,
      research (in its broadest sense) and clinical curiosity should be fostered.

PMID- 18721158
TI  - Emotional outcome after intensive care: literature review.
AB  - AIM: This paper is a report of a literature review to identify (a) the prevalence
      of emotional and psychological problems after intensive care, (b) associated
      factors and (c) interventions that might improve this aspect of recovery.
      BACKGROUND: Being a patient in intensive care has been linked to both short- and
      long-term emotional and psychological consequences. DATA SOURCES: The literature
      search was conducted during 2006. Relevant journals and databases were searched,
      i.e. Medline and CINAHL, between the years 1995 and 2006. REVIEW METHODS: The
      search terms were 'anxiety', 'depression', posttraumatic stress', 'posttraumatic
      stress disorder' and 'intensive care'. RESULTS: Fifteen papers were reviewed
      representing research studies of anxiety, depression and posttraumatic stress,
      and seven that represented intensive care follow-up clinics and patient diaries.
      Being in intensive care can result in significant emotional and psychological
      problems for a number of patients. For the majority of patients, symptoms of
      distress will decrease over time but for a number these will endure for some
      years. Current evidence indicates that emotional problems after intensive care
      are related to both subjective and objective indicators of a patient's intensive
      care experience. Evidence suggests some benefit in an early rehabilitation
      programme, daily sedation withdrawal and the use of patient diaries. However,
      additional research is required to support such findings. CONCLUSION: Our
      understanding of the consequences of intensive care is improving. Psychological
      care for intensive care patients has lagged behind care for physical problems. We
      now need to focus on developing and evaluating appropriate interventions to
      improve psychological outcome in this patient group.

PMID- 18721162
TI  - Transforming wheat vacuolar invertase into a high affinity sucrose:sucrose 1
      fructosyltransferase.
AB  - Vacuolar invertases (VIs) degrade sucrose to glucose and fructose. Additionally,
      the fructan plant wheat (Triticum aestivum) contains different
      fructosyltransferases (FTs), which have evolved from VIs by developing the
      capacity to bind sucrose or fructans as acceptor substrates. Modelling studies
      revealed a hydrogen bonding network in the conserved WMNDPNG motif of VIs, which
      is absent in FTs. In this study, the hydrogen bonding network of wheat VI was
      disrupted by site-directed mutagenesis in the 23WMNDPNG29 motif. While the single
      mutants (W23Y, N25S) showed a moderate increase in 1-kestose production, a
      synergistic effect was observed for the double mutant (W23Y+N25S), showing a 17
      fold increase in transfructosylation capacity, and becoming a real
      sucrose:sucrose 1-fructosyltransferase. Vacuolar invertases are fully saturable
      enzymes, contrary to FTs. This is the first report on the development of a fully
      saturable FT with respect to 1-kestose formation. The superior kinetics (K(m)
      approximately 43 mM) make the enzyme useful for biotechnological applications.
      The results indicate that changes in the WMNDPNG motif are necessary to develop
      transfructosylating capability. The shift towards smaller and/or more hydrophilic
      residues in this motif might contribute to the formation of a specific acceptor
      site for binding of sugar, instead of water.

PMID- 18721164
TI  - An illustrated gardener's guide to transgenic Arabidopsis field experiments.
AB  - Field studies with transgenic Arabidopsis lines have been performed over 8 yr, to
      better understand the influence that certain genes have on plant performance.
      Many (if not most) plant phenotypes cannot be observed under the near constant,
      low-stress conditions in growth chambers, making field experiments necessary.
      However, there are challenges in performing such experiments: permission must be
      obtained and regulations obeyed, the profound influence of uncontrollable biotic
      and abiotic factors has to be considered, and experimental design has to be
      strictly controlled. The aim here is to provide inspiration and guidelines for
      researchers who are not used to setting up such experiments, allowing others to
      learn from our mistakes. This is believed to be the first example of a 'manual'
      for field experiments with transgenic Arabidopsis plants. Many of the challenges
      encountered are common for all field experiments, and many researchers from
      ecological backgrounds are skilled in such methods. There is huge potential in
      combining the detailed mechanistic understanding of molecular biologists with
      ecologists' expertise in examining plant performance under field conditions, and
      it is suggested that more interdisciplinary collaborations will open up new
      scientific avenues to aid analyses of the roles of genetic and physiological
      variation in natural systems.

PMID- 18721163
TI  - Priming defense genes and metabolites in hybrid poplar by the green leaf volatile
      cis-3-hexenyl acetate.
AB  - * Herbivore-induced plant volatiles (HIPVs), in addition to attracting natural
      enemies of herbivores, can serve a signaling function within plants to induce or
      prime defenses. However, it is largely unknown, particularly in woody plants,
      which volatile compounds within HIPV blends can act as signaling molecules. *
      Leaves of hybrid poplar saplings were exposed in vivo to naturally wound-emitted
      concentrations of the green leaf volatile (GLV) cis-3-hexenyl acetate (z3HAC) and
      then subsequently fed upon by gypsy moth larvae. Volatiles were collected
      throughout the experiments, and leaf tissue was collected to measure phytohormone
      concentrations and expression of defense-related genes. * Relative to controls,
      z3HAC-exposed leaves had higher concentrations of jasmonic acid and linolenic
      acid following gypsy moth feeding. Furthermore, z3HAC primed transcripts of genes
      that mediate oxylipin signaling and direct defenses, as determined by both qRT
      PCR and microarray analysis using the AspenDB 7 K expressed sequence tags (EST)
      microarray containing c. 5400 unique gene models. Moreover, z3HAC primed the
      release of terpene volatiles. * The widespread priming response suggests an
      adaptive benefit to detecting z3HAC as a wound signal. Thus, woody plants can
      detect and use z3HAC as a signal to prime defenses before actually experiencing
      damage. GLVs may therefore have important ecological functions in arboreal
      ecosystems.

PMID- 18721165
TI  - Physical activity and overweight in children and adolescents using intensified
      insulin treatment.
AB  - AIM: To describe physical activity and inactivity and parameters associated with
      overweight in a population-based study of children and adolescents on intensive
      insulin treatment. METHODS: Physical activity and inactivity were evaluated in
      723 type 1 diabetic subjects, 240 children aged 6-10 yr and 483 adolescents aged
      11-19 yr, using a questionnaire that can estimate total amount of time spent on
      inactivity and light, moderate and vigorous activity. RESULTS: Overall, 54% of
      the participants do not fulfil the international recommendations of 60 min of
      moderate-to-vigorous activity per day. Girls are less active than boys in
      childhood (70 vs. 88 min/d, p = 0.01) and in adolescence (47 vs. 57 min/d, p =
      0.02). Furthermore, this study shows that those who are more active are also
      those who seldom skip meals (p < 0.001). Forty-three percent of the participants
      watch TV for more than 2 h a day, and TV viewing was found to be related to
      overweight in children and adolescents with type 1 diabetes [OR: 2.5 (1.40-4.54),
      p = 0.002]. No statistical differences in physical activity were noted between
      the different intensified insulin regimens. Patients wearing insulin pumps were
      not less active. CONCLUSION: To increase physical activity to recommended level
      and limit TV viewing should be an important issue in education of all children
      and adolescents with type 1 diabetes, independent of insulin regimen.

PMID- 18721166
TI  - Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle
      intervention in insulin-resistant adolescents.
AB  - The presence of fatty liver per ultrasound and liver-associated enzymes were
      measured in a select cohort of youth with both obesity and insulin resistance,
      and the effect of metformin on these parameters evaluated. Fifty obese,
      multiethnic, insulin-resistant adolescents (mean age 15.1 yr, mean body mass
      index 39.8 kg/m2) were randomized to receive lifestyle recommendations plus
      either twice per day doses of 850 mg of metformin or placebo. Fasting and post
      glucose challenge biochemistries and liver ultrasounds were compared at baseline
      and 6 months. The prevalence of fatty liver was 74%, elevated alanine
      aminotransferase (ALT) 14%, aspartate aminotransferase (AST) 14%, and gamma
      glutamyl transferase (GGT) 17%. Fatty liver was mild in 23%, moderate in 31%, and
      severe in 46%. Fatty liver was more common in male and Hispanic subjects and
      elevated ALT more common in Hispanic subjects. Subjects with fatty liver appeared
      more insulin resistant (higher fasting insulin and triglycerides, lower high
      density lipoprotein cholesterol) and had higher ALT and AST. At 6 months, mean
      ALT, GGT, and fasting insulin improved significantly in all subjects. Fatty liver
      prevalence (p < 0.04), severity (p < 0.04), and fasting insulin (p < 0.025)
      improved significantly with metformin compared to placebo. Non-alcoholic fatty
      liver disease (NAFLD) occurs with a high prevalence and severity in obese,
      insulin-resistant adolescents. While metformin plus lifestyle intervention
      appears promising, defining NAFLD therapies capable of preventing fibrosis and
      cirrhosis requires further study.

PMID- 18721167
TI  - A multisite trial of a clinic-integrated intervention for promoting family
      management of pediatric type 1 diabetes: feasibility and design.
AB  - The feasibility of a family-based clinic-integrated behavioral intervention to
      improve family management of type 1 diabetes was evaluated. In each of four
      clinical sites, 30-32 families (a total of 122) were randomized to intervention
      or usual care comparison groups. The WE*CAN intervention, based on family problem
      solving methods, was delivered during three routine clinic visits by trained
      'Health Advisors'. Of eligible families across the four sites, 83% agreed to
      participate, of whom 96% completed the baseline, mid-term, and postintervention
      assessments. Families participated in an average of 2.85 intervention sessions
      over an 8-month period. The intervention was integrated into the clinic setting
      without impairing clinic flow and was implemented with fidelity and consistency
      across sites by trained non-professionals. The findings provide evidence of the
      feasibility of conducting a multisite trial to evaluate the effects of a clinic
      integrated problem-solving intervention to improve family management. Many
      lessons were learned that provide guidance for recruitment, measurement, and
      intervention for the larger clinical trial.

PMID- 18721168
TI  - Improved treatment satisfaction but no difference in metabolic control when using
      continuous subcutaneous insulin infusion vs. multiple daily injections in
      children at onset of type 1 diabetes mellitus.
AB  - OBJECTIVE: The aim of this study was to compare safety, metabolic control, and
      treatment satisfaction in children/adolescents at onset of type 1 diabetes
      mellitus who were treated with either continuous subcutaneous insulin infusion
      (CSII) or multiple daily injections (MDI). RESEARCH DESIGN AND METHODS: Seventy
      two children/adolescents (7-17 yr of age) were enrolled in this open, randomized,
      parallel, multicenter study. Approximately half of the patients were treated with
      MDI (natural protamine hagedorn [NPH] insulin twice daily and rapid-acting
      insulin three to -four times daily, n = 38) by pen, and the other half received
      CSII (n = 34). The patients were followed for 24 months with clinical visits at
      the entry of the study and after 1, 6, 12, and 24 months. During these visits,
      hemoglobin A1c, insulin doses, weight, and height were registered. Severe
      episodes of hypoglycemia and ketoacidosis as well as technical problems were
      recorded. In addition, the patients/parents answered the Diabetes Treatment
      Satisfaction Questionnaire. RESULTS: There was no significant difference in
      metabolic control between the treatment groups. Treatment satisfaction was
      significantly higher in the group treated with CSII compared with the MDI group
      (p <or= 0.01 at all screening visits). There were no episodes of ketoacidosis and
      there was no significant difference regarding severe hypoglycemia between the
      treatment groups. CONCLUSIONS: CSII treatment proved to be a safe therapy in
      children/adolescents followed for 24 months after onset of their diabetes.
      Treatment satisfaction was higher in the CSII group, although there was no
      difference in metabolic control compared with the MDI group.

PMID- 18721169
TI  - IgE-mediated hypersensitivity: patients with complex regional pain syndrome type
      1 (CRPS1) vs the Dutch population. A retrospective study.
AB  - OBJECTIVE: To investigate whether hypersensitivity is more common in Complex
      Regional Pain Syndrome type 1 (CRPS1) patients than in the general population. In
      a recent study, the level of tryptase, a specific marker for mast cells, was
      significantly higher in blister fluid from the involved extremity of CRPS1
      patients. This suggested that mast cells may play a role in the pathophysiology
      of CRPS1. Mast cells are major effectors in allergic reactions, and are also
      involved in a variety of noninfectious inflammatory diseases. Patients. Sixty-six
      Dutch patients with CRPS1 in one extremity were included. OUTCOME MEASURES:
      Allergy information was obtained from the medical history and a modified
      questionnaire based on the Europees Luchtweg Onderzoek Nederland 1 study. Total
      IgE and allergen-specific IgE were measured from blood samples. Also tryptase, as
      a marker for mast cells, was measured. The data from the questionnaire were
      compared with that of the general Dutch population, and the plasma levels were
      compared with reference values and data in the literature. RESULTS: The medical
      history did not differ from information provided in the questionnaire by the
      CRPS1 group. There was no significant difference between the answers to the
      questionnaire between the CRPS1 patients and the general population. The total
      IgE levels were elevated in 30% of the CRPS1 patients compared with 15-24% of the
      general population, and allergen-specific IgE and tryptase levels were comparable
      with the reference values. CONCLUSIONS: Based on the medical history, an allergy
      questionnaire, and objective laboratory findings we conclude that IgE-mediated
      hypersensitivity is not more common in CRPS1 patients than in the general
      population.

PMID- 18721170
TI  - The prevalence, severity, and impact of opioid-induced bowel dysfunction: results
      of a US and European Patient Survey (PROBE 1).
AB  - OBJECTIVE: This multinational, Internet-based survey was designed to assess the
      prevalence, frequency, severity, and impact of opioid-induced bowel dysfunction
      (OBD) in patients receiving opioid therapy for chronic pain and taking laxatives.
      DESIGN: In total, 322 patients taking daily oral opioids and laxatives completed
      the 45-item questionnaire. At the time of the survey, 45% of patients reported <3
      bowel movements per week. The most prevalent opioid-induced side effects were
      constipation (81%) and straining to pass a bowel movement (58%). Those side
      effects considered most bothersome by patients were (in order of rank)
      constipation, straining, fatigue, small or hard bowel movements, and insomnia.
      RESULTS: Most of the OBD symptoms specified in the questionnaire were experienced
      by the majority of patients >or=4 times a week. Constipation was the OBD symptom
      that was most often reported as severe. Most patients reported that their OBD
      symptoms had at least a moderate negative impact on their overall quality of life
      and activities of daily living. A third of patients had missed, decreased or
      stopped using opioids in order to make it easier to have a bowel movement.
      CONCLUSION: The survey findings confirm that OBD occurs frequently, despite the
      use of laxatives, in individuals taking daily oral opioids for chronic pain.
      These gastrointestinal symptoms add to the burden already experienced by chronic
      pain patients, negatively impacting quality of life and, in some cases, affecting
      opioid treatment itself.

PMID- 18721171
TI  - Effects of smoking status on immediate treatment outcomes of multidisciplinary
      pain rehabilitation.
AB  - OBJECTIVE: The primary aim of this study was to determine the effects of smoking
      on treatment outcomes following multidisciplinary pain rehabilitation. A
      secondary aim was to assess the tobacco use characteristics of smokers with
      chronic pain. DESIGN: A prospective, nonrandomized, repeated measures design.
      SETTING: Multidisciplinary pain rehabilitation center at a tertiary referral
      medical center. PATIENTS: All patients (N = 193) consecutively admitted from
      August 2005 through February 2006. INTERVENTIONS: A 3-week outpatient
      multidisciplinary pain rehabilitation program. OUTCOME MEASURES: The
      Multidimensional Pain Inventory (MPI), Short Form-36 Health Status Questionnaire
      (SF-36), Center for Epidemiologic Studies-Depression scale (CES-D), Pain Anxiety
      Symptom Scale (PASS-20) and Pain Catastrophizing Scale (PCS) were administered at
      admission and dismissal. RESULTS: The study involved 49 (83% women) smokers and
      144 (83% women) nonsmokers. The mean number of cigarettes smoked daily was 17.5
      (SD 11.1) and the mean duration of smoking was 21.5 years (SD 12.1). After
      adjusting for demographic differences, repeated measures of analysis of
      covariance showed a main effect of smoking status for MPI affective distress (P =
      0.008), CES-D (P = 0.001) and PCS (P = 0.011). An interaction of smoking status
      and time was found for the PASS-20 (P = 0.028), MPI affective distress (P =
      0.033), MPI life control (P = 0.003) and SF-36 role-emotional (P = 0.004)
      subscale. While the majority of smokers were ready to consider smoking
      abstinence, 43% declined a brief smoking cessation intervention. CONCLUSIONS: In
      this series of patients undergoing multidisciplinary treatment for chronic pain,
      immediate treatment effects for a variety of outcome measures were similar or
      significantly better in smokers compared with nonsmokers.

PMID- 18721172
TI  - Ventral innervation of the lateral C1-C2 joint: an anatomical study.
AB  - OBJECTIVE: Clinical observation has suggested the presence of ventral cervical
      extra-articular pain pathways in patients with C1-C2 joint pain. However, the
      existence of ventral innervation to the C1-C2 joint has not been documented. The
      objective of this study was to determine whether ventral innervation to the
      lateral C1-C2 joint exists, and to describe its relational anatomy. DESIGN: Gross
      and microscopic dissection was performed on 11 embalmed human cadavers. Wire
      segments were placed on identified ventral plexus nerves and radiographic imaging
      obtained in multiple planes. Histologic staining of prevertebral plexus nerves
      was performed with Osmium and compared with tissue controls. RESULTS: A
      superficial and deep cervical prevertebral plexus was identified terminating in
      the ventral joint capsule of the C1-C2 joint in all cadavers examined (21 sides).
      The location of the deep cervical prevertebral plexus was consistent within the
      C2 ventral gutter. Osmium staining confirmed the presence of myelin in plexus
      specimens. CONCLUSION: In this study, two cervical prevertebral plexuses
      (superficial and deep) were identified that have not previously been described.
      Terminal branches of the plexuses entered the ventral joint capsule of the
      lateral C1-C2 joint and were seen approaching the dens. Findings provide and
      explanation for the clinical observation that electrical stimulation in the C2
      ventral gutter can reproduce headache in patients with C1-C2 joint pain.

PMID- 18721173
TI  - Gabapentin toxicity in renal failure: the importance of dose adjustment.
AB  - OBJECTIVE: This case report outlines a significant type of morbidity due to
      continued use of gabapentin during an episode of acute renal failure. Setting.
      University teaching hospital. DISCUSSION: Gabapentin is widely used in the
      management of pain. It is entirely excreted through the renal system so this
      needs to be considered in any patient becoming acutely ill and developing renal
      failure. We describe a patient who developed significant deterioration in her
      conscious level due to iatrogenic gabapentin overdose. CONCLUSION: All doctors
      need to be aware of the need to review the indications for gabapentin use during
      periods of acute illness, especially with regard to renal impairment. Off-label
      use should be discouraged.

PMID- 18721174
TI  - Reported lifetime aberrant drug-taking behaviors are predictive of current
      substance use and mental health problems in primary care patients.
AB  - BACKGROUND: The aim of this report is to determine the frequency of aberrant drug
      behaviors and their relationship to substance abuse disorders in a large primary
      sample of patients receiving opioids for chronic pain. METHODS: The data utilized
      for this report was obtained from 904 chronic pain patients receiving opioid
      therapy from their primary care physician. A questionnaire was developed based on
      12 aberrant drug behaviors reported in the clinical literature. The diagnosis of
      a current substance use disorder was determined using Diagnostic and Statistical
      Manual of Mental Disorders-Fourth Edition(DSM-IV) criteria. RESULTS: The average
      duration of chronic pain in the sample was 16 years and for opioid therapy, 6.4
      years. Of the patients, 80.5% reported one or more lifetime aberrant drug
      behaviors. The most frequent behaviors reported included early refills (41.7%),
      increase dose without physician consent (35.7%), and felt intoxicated from
      opioids (32.2%). Only 1.1% of subjects with 1-3 aberrant behaviors (N = 464,
      51.2%) met DSM-IV criteria for current opioid dependence compared with 9.9% of
      patients with four or more behaviors (N = 264, 29.3%). Persons with positive
      urine toxicology tests for cocaine were 14 times more likely to report four or
      more behaviors than no behaviors (14.1% vs 1.1%). A logistic model found that
      subjects who reported four or more aberrant behaviors were more likely to have a
      current substance use disorder (odds ratio [OR] 10.14; 3.72, 27.64), a positive
      test for cocaine (odds ratio [OR] 3.01; 1.74, 15.4), an Addiction Severity Index
      (ASI) psychiatric composite score >0.5 (OR 2.38; 1.65, 3.44), male gender (OR
      2.08: 1.48, 2.92), and older age (OR 0.69; 0.59, 0.81) compared with subjects
      with three or fewer behaviors. Pain levels, employment status, and morphine
      equivalent dose do not enter the model. CONCLUSIONS: Patients who report four or
      more aberrant drug behaviors are associated with a current substance use disorder
      and illicit drug use, whereas subjects with up to three aberrant behaviors have a
      very low probability of a current substance abuse disorder. Four behaviors-
      oversedated oneself, felt intoxicated, early refills, increase dose on own-
      appear useful as screening questions to predict patients at greatest risk for a
      current substance use disorders.

PMID- 18721176
TI  - The confusion assessment method--a tool for delirium detection by the acute pain
      service.
AB  - INTRODUCTION: Delirium is an acute fluctuating disturbance in cognitive status,
      linked to increased morbidity and mortality. The purpose of this pilot study was
      to assess the feasibility in terms of required time and yield of delirium
      monitoring by the Acute Pain Service (APS) using the Confusion Assessment Method
      for Intensive Care Unit instrument. METHODS: Patients undergoing surgery
      requiring more than 2 days of hospital stay were recruited. Each patient was
      assessed daily for 2 days after surgery using the Confusion Assessment Method for
      Intensive Care Unit. Patients were also assessed for orientation to person,
      place, and time. Any notes of confusion or delirium made by physicians or nursing
      staff were gathered. RESULTS: 145 patients were recruited. Each patient encounter
      required an average 2.3 +/- 0.3 minutes for the assessment (95% CI). The
      incidence of delirium within 2 days after surgery was 7.6%. Only 18% of the
      patients diagnosed with delirium by the APS were noted as being confused by the
      medical or nursing staff. CONCLUSIONS: The use of this tool required little
      training, and only 2 minutes per patient. It detected more patients with delirium
      than did the standard nursing assessments or other patient-clinician
      interactions. The use of this instrument by the pain service was feasible in
      terms of time consumption and most likely would be valuable in its yield. Early
      detection may help in initiating prompt treatment, eliminating known risk factors
      and thus reducing morbidity.

PMID- 18721175
TI  - Radiofrequency and pulsed radiofrequency treatment of chronic pain syndromes: the
      available evidence.
AB  - There are currently 6 reviews on (pulsed) radiofrequency (RF) for the management
      of spinal pain. Two reviews on interventional pain management techniques in
      general also discuss RF. The outcomes of those reviews depend on the type of
      studies included and the opinion of the reviewers, which may result in different
      evidence levels. Radiofrequency denervation at the cervical and lumbar level has
      produced the most solid evidence. The differences in treatment outcome registered
      in the 5 randomized controlled trials (RCTs) regarding lumbar facet denervation
      can be attributed to differences in patient selection and/or inappropriate
      technique. There is not sufficient evidence supporting the use of RF facet
      denervation for the management of cervicogenic headache. The studies examining
      the management of cervical radicular pain suggest a comparable efficacy for RF
      and pulsed RF (PRF). The PRF treatment is supposed to be safer and therefore
      should be preferred. The superiority of RF treatment adjacent to the lumbar
      dorsal root ganglion for the management of lumbar radicular pain has not been
      demonstrated in an RCT. Information regarding RF treatment of sacroiliac joint
      pain is accumulating. No randomized sham-controlled trials on the value of RF
      treatment of the Gasserian ganglion for the management of idiopathic trigeminal
      neuralgia have been published. One RCT indicates superiority of RF over PRF for
      the management of idiopathic trigeminal neuralgia. Future research to confirm or
      deny the efficacy of (P)RF should be conducted in carefully selected patient
      populations. The tests used for patient inclusion in such a trial could
      potentially help the clinician in selecting patients for this type of treatment.
      The value of PRF treatment of the peripheral nerves also needs to be confirmed in
      well-designed trials.

PMID- 18721178
TI  - Aging and electrocortical response to error feedback during a spatial learning
      task.
AB  - Event-related potentials were collected as older and younger adults responded to
      error feedback in an adaptation of the Groton Maze Learning Test, an age
      sensitive measure of spatial learning and executive skills expected to maximally
      involve anterior cingulate cortex (ACC). Older adults made more errors and
      produced smaller feedback-related negativities (FRNs) than young controls. LORETA
      source localization revealed that, for young adults, neural activation associated
      with the FRN was focused in ACC and was stronger to negative feedback. Older
      adults responded with less intense and less differentiated ACC activation, but
      FRN amplitudes did relate to error rate for the most difficult mazes. The
      feedback P3 was sensitive to negative feedback but played no role in the
      prediction of error for either group. These data reflect the selective age
      related decline of ACC response but also its continued contribution to
      performance monitoring in aging.

PMID- 18721177
TI  - Acute monoplegia after lysis of epidural adhesions: a case report.
AB  - Lysis of epidural adhesions is an interventional procedure performed to treat
      refractory low back pain or radicular pain due to epidural scarring. A 39-year
      old female with a diagnosis of failed back surgery syndrome underwent lysis of
      epidural adhesions using a Racz catheter. She developed acute monoplegia of her
      right lower extremity immediately after the procedure. Radiographic imaging did
      not reveal an epidural hematoma. Motor and sensory function in the right lower
      limb returned after 5 days. Large volumes of fluid injected during neuroplasty
      could have caused transient nerve injury from compression within loculated
      epidural compartments.

PMID- 18721180
TI  - Treatment of bilateral spontaneous pneumothorax: the catheter drainage method is
      still useful!

PMID- 18721181
TI  - Should lung transplant recipients routinely perform airway clearance techniques?
      A randomized trial.
AB  - BACKGROUND AND OBJECTIVE: Despite the widespread use of airway clearance (AC)
      techniques to clear excessive secretions and improve lung function, little is
      known about their efficacy following lung transplantation (LTx). This study
      compared the effects of two AC strategies (proactive vs reactive) on a range of
      clinical outcomes following LTx. METHODS: A prospective randomized trial was
      conducted. Uncomplicated patients were recruited 1 month postoperatively.
      Patients performed AC using positive expiratory pressure either twice daily
      (proactive strategy) or only in the presence chest infection (reactive strategy).
      Lung function (FEV(1) and FVC), CXR (Brasfield score) and bronchoscopic airway
      characteristics (anastomotic healing, patency and secretions) were assessed at 1,
      2 and 3 months postoperatively. Adherence was measured. RESULTS: Of 60
      consecutive patients, 36 (18 proactive, 18 reactive) were recruited and completed
      the study. Both groups improved lung function (FEV(1) 72 +/- 4% to 81 +/- 4%, P <
      0.0001; FVC 69 +/- 3% to 81 +/- 3%, P < 0.0001) and Brasfield scores (17.8 +/-
      0.5 to 19.8 +/- 0.5, P < 0.002) over the study period. No significant differences
      for any outcome were found between the two groups. The vast majority of patients
      had fully healed, 100% patent anastomoses without secretions at 3 months. There
      were no significant differences between the two groups in airway characteristics
      and the incidence of chest infection. Adherence to both strategies was high (84%
      proactive, 100% reactive). CONCLUSIONS: Proactive AC following lung
      transplantation was not associated with a reduced incidence of respiratory
      infection, alteration of CXR findings or improvement in airway characteristics.

PMID- 18721182
TI  - Angiogenic cytokines in induced sputum of patients  with sarcoidosis.
AB  - BACKGROUND AND OBJECTIVE: Sarcoidosis is a systemic granulomatous disorder of
      unknown aetiology involving multiple organs and often associated with non
      granulomatous microangiopathic lesions in various organs. Increased angiogenesis
      inducing ability of activated alveolar macrophages was found in bronchoalveolar
      specimens from patients with pulmonary sarcoidosis and from patients with
      extrapulmonary involvement. In contrast, decreased levels of vascular endothelial
      growth factor (VEGF) were found in BAL fluid recovered from sarcoid-associated
      pulmonary fibrosis. This study evaluated whether sarcoidosis is associated with
      abnormalities of VEGF and IL-8 in induced sputum (IS) samples. METHODS: Twenty
      three sarcoid patients and 13 controls performed IS. CD4/CD8 T-cell subsets were
      measured, as were pulmonary function tests and VEGF and IL-8. RESULTS: Sarcoid
      patients showed significantly higher mean %lymphocytes (P = 0.04), significantly
      higher mean CD4/CD8 ratio (P = 0.0001) and significantly lower VEGF levels (P =
      0.03) than controls. Patients with stages III-IV sarcoidosis showed a lower level
      of VEGF compared with those with stages I-II sarcoidosis (P = 0.048). IL-8 was
      detected in 10/35 samples and positively correlated with % neutrophils (P =
      0.054) and eosinophils (P = 0.045). VEGF immunohistochemical staining showed a
      mixed pattern of expression in the same tissue samples and was low in fibrotic
      tissue areas. CONCLUSION: VEGF in IS samples may reflect impairment in
      angiogenesis associated with the extent of sarcoid fibrosis and functional
      disorders.

PMID- 18721183
TI  - Effect of early versus late intervention with inhaled  corticosteroids on airway
      wall thickness in patients with asthma.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to determine whether early
      versus late initiation of long-term inhaled corticosteroid (ICS) therapy
      decreases airway wall thickness in patients with asthma. METHODS: One hundred and
      eighty-one patients with asthma not previously treated with ICS were given
      inhaled budesonide for 1 year. These patients were divided into five groups
      according to the duration of their asthma symptoms, which ranged from less than 1
      year to more than 10 years. High-resolution CT images and post-bronchodilator
      FEV1 were examined before and 1 year after treatment. RESULTS: Before treatment,
      airway wall thickness was increased relative to the duration of asthma. Disease
      severity improved with ICS treatment even in patients who had suffered asthma
      symptoms for more than 10 years. Post ICS treatment, airway wall thickness
      decreased in patients with a duration of symptoms less than 3 years, and a minor
      response was seen in patients with a duration of symptoms from 3 to 5 years.
      However, there was no change in airway wall thickness in patients who had
      suffered asthma for more than 5 years. Post-bronchodilator FEV1 improved only in
      patients who had suffered asthma for less than 3 years. CONCLUSIONS: ICS therapy
      may improve asthma control in all asthma patients despite the disease duration,
      but early ICS treatment may be critical to reverse airway wall thickening
      associated with asthma.

PMID- 18721184
TI  - Haemoglobin adjustments to define anaemia.
AB  - OBJECTIVE: To provide researchers with an unambiguous definition of anaemia using
      haemoglobin. METHODS: Review of recommendations by expert groups and review of
      the literature. RESULTS: This report provides an unambiguous approach to
      haemoglobin adjustments to define anaemia using international criteria. When
      determining anaemia using haemoglobin, it is important to account for pregnancy,
      altitude, cigarette smoking, and possibly ethnicity after removing unlikely
      values. These haemoglobin adjustments are presented. CONCLUSION: Recommendations
      for defining extreme haemoglobin values and for reporting anaemia and haemoglobin
      results are provided, and software programs to determine anaemia are described.

PMID- 18721185
TI  - Recurrent costs of HIV/AIDS-related health services in Rwanda: implications for
      financing.
AB  - OBJECTIVE: To estimate recurrent costs per patient and costs for a national
      HIV/AIDS treatment programme model in Rwanda. METHODS: A national HIV/AIDS
      treatment programme model was developed. Unit costs were estimated so as to
      reflect necessary service consumption of people living with HIV/AIDS (PLWHA). Two
      scenarios were calculated: (1) for patients/clients in the year 2006 and (2) for
      potential increases of patients/clients. A sensitivity analysis was conducted to
      test the robustness of results. RESULTS: Average yearly treatment costs were
      estimated to amount to 504 US$ per patient on antiretroviral therapy (ART) and to
      91 US$ for non-ART patients. Costs for the Rwandan HIV/AIDS treatment programme
      were estimated to lie between 20.9 and 27.1 million US$ depending on the
      scenario. ART required 9.6 to 11.1 million US$ or 41-46% of national programme
      costs. Treatment for opportunistic infections and other pathologies consumed 7.1
      to 9.3 million US$ or 34% of total costs. CONCLUSION: Health Care in general and
      ART more specifically is unaffordable for the vast majority of Rwandan PLWHA.
      Adequate resources need to be provided not only for ART but also to assure
      treatment of opportunistic infections and other pathologies. While risk-pooling
      may play a limited role in the national response to HIV/AIDS, considering the
      general level of poverty of the Rwandan population, no appreciable alternative to
      continued donor funding exists for the foreseeable future.

PMID- 18721186
TI  - TB, HIV-associated TB and multidrug-resistant TB on Thailand's border with
      Myanmar, 2006-2007.
AB  - OBJECTIVE: To measure the burden and improve management of tuberculosis (TB), HIV
      associated TB and MDR TB in Tak Province, Thailand, which borders Myanmar.
      METHODS: From September 2006 to August 2007, we collected uniform data about TB
      cases and enhanced human immunodeficiency virus (HIV) counselling and testing. We
      provided mycobacterial culture and drug-susceptibility testing in public or non
      governmental organization facilities. Patients were classified by nationality
      and, for non-Thais, by migration status. RESULTS: Of 1662 TB cases in the 12
      month period, 1087 (65%) occurred in non-Thais. Of non-Thais, 415 (38%) lived in
      Myanmar but crossed the border for healthcare. HIV infection was diagnosed in 18%
      of Thais compared with 12% of non-Thais (P < 0.01); HIV status was unknown for
      22% of Thais and 27% of non-Thais (P = 0.02). Overall, multidrug-resistant (MDR)
      TB was diagnosed in 27 patients, 19 (70%) in non-Thais. Among TB cases never
      previously treated for TB, no MDR cases were diagnosed in Thais or in Myanmar
      refugees, but six cases were diagnosed in migrants from Myanmar. CONCLUSIONS: In
      Thailand, TB, HIV-associated TB and MDR TB in migrants from Myanmar are important
      public health problems; they need to be resolved in both the countries.

PMID- 18721187
TI  - Causes of deaths using verbal autopsy among adolescents and adults in rural
      western Kenya.
AB  - OBJECTIVE: To establish causes and patterns of deaths among adolescents and
      adults (age >11 years) using verbal autopsy (VA) in a rural area of western Kenya
      where malaria and HIV are common. METHODS: Village reporters reported all deaths
      in Asembo and Gem (population 135 000), an area under routine demographic
      surveillance. After an interval of >/=1 month, a trained interviewer used a
      structured questionnaire to ask the caretaker about signs and symptoms that
      preceded death. Three clinical officers independently reviewed the interviews and
      assigned two unranked causes of death; a common cause was designated as the cause
      of death. RESULTS: In 2003, 1816 deaths were reported from residents; 48% were
      male and 72% were between 20 and 64 years of age. Most residents (97%) were ill
      before death, with 60% of illnesses lasting more than 2 months; 87% died at home.
      Care was sought by 96%; a health facility was the most common source, visited by
      73%. For 1759 persons (97%), a common cause of death was designated. Overall, 74%
      of deaths were attributed to infectious causes. HIV (32%) and tuberculosis (TB)
      (16%) were the most frequent, followed by malaria, respiratory infections,
      anaemia and diarrhoeal disease (approximately 6% each). Death in a health
      facility was associated with young age, higher education, higher SES, a non
      infectious disease cause and a shorter duration of illness. CONCLUSION: In this
      area, the majority of adult and adolescent deaths were attributed to potentially
      preventable infectious diseases. Deaths in health facilities were not
      representative of deaths in the community. Programmes to prevent HIV and TB
      infection and to decrease mortality have started. Their impact can be evaluated
      against this baseline information.

PMID- 18721188
TI  - Development and testing of a de novo clinical staging system for podoconiosis
      (endemic non-filarial elephantiasis).
AB  - OBJECTIVE: To develop and test a robust clinical staging system for podoconiosis,
      a geochemical disease in individuals exposed to red clay soil. METHODS: We
      adapted the Dreyer system for staging filarial lymphoedema and tested it in four
      re-iterative field tests conducted in an area of high-podoconiosis prevalence in
      Southern Ethiopia. The system has five stages according to proximal spread of
      disease and presence of dermal nodules, ridges and bands. We measured the 1-week
      repeatability and the inter-observer agreement of the final staging system.
      RESULTS: The five-stage system is readily understood by community workers with
      little health training. Kappa for 1-week repeatability was 0.88 (95% CI 0.80
      0.96), for agreement between health professionals was 0.71 (95% CI 0.60-0.82),
      while that between health professionals and community podoconiosis agents without
      formal health training averaged 0.64 (95% CI 0.52-0.78). CONCLUSIONS: This simple
      staging system with good inter-observer agreement and repeatability can assist in
      the management and further study of podoconiosis.

PMID- 18721189
TI  - New concepts on erythema annulare centrifugum: a clinical reaction pattern that
      does not represent a specific clinicopathological entity.
AB  - BACKGROUND: Erythema annulare centrifugum (EAC) is considered an inflammatory
      skin disease with unknown aetiology. In most textbooks it is assigned to the
      incoherent conglomeration of figurate or gyrate erythemas. OBJECTIVES: To re
      evaluate a large cohort of patients with EAC and to assess the evidence for
      infection with Borrelia. METHODS: We retrospectively investigated 90 cases with
      the diagnosis of EAC. Haematoxylin and eosin sections were re-examined and
      diagnoses were specified; these were then confirmed by clinicopathological
      correlation. Infection with Borrelia was assessed by focus-floating microscopy
      and by a Borrelia-specific polymerase chain reaction (PCR). RESULTS: Besides a
      miscellaneous group of annular disorders at times confused with EAC such as
      urticaria, leucocytoclastic vasculitis and psoriasis (20 of 90; 22%), EAC
      appeared to serve as a collective term for three main clinicopathological
      reaction patterns: (i) (tumid) lupus erythematosus (29 of 90; 32%), (ii)
      spongiotic dermatitides (25 of 90; 28%) and (iii) pseudolymphoma (16 of 90; 18%).
      In 13 of 16 (81%) cases with a pseudolymphomatous reaction pattern spirochaetes
      stained positive but were negative in other reaction patterns of EAC as well as
      in negative controls. These findings were confirmed by a Borrelia-specific PCR
      which was positive in two of three (67%) of these pseudolymphomatous EAC cases
      but was negative in all other variants of EAC (none of five) as well as 20
      controls. CONCLUSIONS: We conclude that 'EAC' is a clinical reaction pattern that
      does not represent a specific clinicopathological entity and should lead to
      consideration of mainly lupus erythematosus, dermatitis and, in some cases,
      cutaneous Lyme disease.

PMID- 18721190
TI  - How prominent are patient-reported outcomes in clinical trials of dermatological
      treatments?
AB  - BACKGROUND: Assessment of symptoms or disease improvement by study participants
      is an important aspect of assessing new dermatological therapies in clinical
      trials, especially for chronic skin diseases that lack objective severity
      markers. OBJECTIVES: We sought to determine the frequency and prominence of
      reporting of participants' subjective efficacy outcomes in dermatological
      clinical trials. Our secondary objective was to determine whether participant and
      physician outcomes agree in terms of direction and magnitude. METHODS: Systematic
      review of 125 randomized controlled trials identified from the Archives of
      Dermatology, British Journal of Dermatology, Clinical & Experimental Dermatology,
      Journal of Dermatological Treatment and Journal of the American Academy of
      Dermatology published between 1994 and 2001 (25 from each). Studies were
      retrieved in hard copy from the Cochrane Skin Group specialized register of
      trials and data were abstracted and summarized. RESULTS: Participant efficacy
      outcomes were mentioned in some form in only 32 of 125 trials (25.6%, 95% exact
      confidence interval 18.2-34.2%). Of these 32 studies, participant outcomes were
      mentioned only in the methods section in two studies, in the methods and results
      section without further data in nine studies and with further data in 21. Data
      were presented in figure format only in 12 of these studies and in tables and
      figures in nine. Participant efficacy outcomes were mentioned in the abstract
      section in just over half (53%) of the 32 trials that included participant
      efficacy outcomes. There was not enough information to assess agreement in
      direction and magnitude of participant vs. assessor outcomes. Overall, only 17
      papers (13.6%) clearly declared their main outcome measures beforehand in the
      introduction or methods section. CONCLUSIONS: Asking study participants for their
      views of treatment efficacy seems like a good idea in dermatological clinical
      trials, yet only about a quarter of the trials examined in this review did so.
      Even when such information was recorded, it was often poorly and incompletely
      reported and given low prominence within the trial report. Our study findings
      call for a more comprehensive uptake for including participant efficacy outcomes
      alongside other assessor outcomes in clinical trials and, when included, to
      report those outcomes in full.

PMID- 18721191
TI  - Periorbital dermatitis--a recalcitrant disease: causes and differential
      diagnoses.
AB  - BACKGROUND: Periorbital dermatitis is common and frequently recalcitrant to
      treatment. Due to the exposed and visible location, patients often suffer
      severely from periorbital dermatitis. OBJECTIVES: To determine the frequency and
      causes of periorbital dermatitis including contact sensitizers. METHODS: We
      investigated two cohorts of patients (Erlangen and IVDK without Erlangen) between
      1999 and 2004. RESULTS: The differences between the two cohorts with periorbital
      dermatitis [Department of Dermatology at University Hospital Erlangen (n = 88)
      and the German Information Network of Departments of Dermatology (IVDK)
      collective (n = 2035)] were determined by the MOAHLFA (male, occupational
      dermatosis, atopic eczema, hand dermatitis, leg dermatitis, facial dermatitis,
      age > or = 40 years) index. Statistically significant factors for periocular
      eczema are female sex, atopic skin diathesis and age > or = 40 years. In both
      cohorts allergic contact dermatitis was the main cause of periorbital eczema
      (Erlangen 44.3%, IVDK 31.6%), followed by periorbital atopic dermatitis (Erlangen
      25%, IVDK 14.1%), airborne dermatitis (Erlangen 10.2%, IVDK 1.9%), irritant
      contact dermatitis (Erlangen 9.1%, IVDK 7.6%), periorbital rosacea (Erlangen
      4.5%, IVDK 2.2%), allergic conjunctivitis (Erlangen 2.3%, IVDK included in
      'others') and psoriasis (Erlangen 2.3%, IVDK included in 'others'). The most
      relevant allergens/allergen sources inducing periorbital eczema were consumers'
      products (facial cream, eye shadow and ophthalmic therapeutics) (31%), fragrance
      mix (19%), balsam of Peru (10%), thiomersal (10%) and neomycin sulphate (8%);
      12.5% of patients with allergic periocular dermatitis could be exclusively
      elucidated by testing patients' own products. CONCLUSIONS: Our data demonstrate
      the multiplicity of causes for periorbital eczematous disease manifestation,
      which requires patch testing of standard trays as well as consumers' products to
      elucidate the relevant contact sensitization.

PMID- 18721192
TI  - Selective venous sampling for androgen-producing ovarian pathology.
AB  - OBJECTIVE: Multiple diagnostic modalities may be needed to establish the source
      of excessive androgen production in women. The role of selective venous
      catheterization in this process has not been established fully. DESIGN: A study
      of hyperandrogenaemic subjects and literature review. PATIENTS: Four
      hyperandrogenaemic women and an additional 132 previously reported cases with
      available testing data and a pathological diagnosis were evaluated. MEASUREMENTS:
      Serum androgens, diagnostic imaging and ovarian venous effluent sampling.
      Criteria to distinguish ovarian tumours from other ovarian conditions and to
      localize the lesion(s) were evaluated. RESULTS: Basal peripheral testosterone
      levels >or= 4.51 nmol/l (>or= 130 ng/dl) discriminated ovarian tumours from
      benign causes of hyperandrogenism (sensitivity: 93.8%, 95% CI 85.0-98.2;
      specificity: 77.8%, 95% CI 66.4-86.7). Single lesions produced higher ipsilateral
      testosterone concentrations (612.6 +/- 162.0 nmol/l; 17 653 +/- 4670 ng/dl)
      compared to contralateral values (26.4 +/- 5.2 nmol/l; 761 +/- 150 ng/dl). In
      women with peripheral testosterone >or= 4.51 nmol/l, a right-to-left (R:L)
      ovarian testosterone ratio >or= 1.44 correctly identified all 18 women with right
      sided tumours and misclassified two with bilateral lesions; 12 out of 14 women
      with left-sided or bilateral lesions had a lower R:L value. When this criterion
      was combined with a left-to-right (L:R) ovarian testosterone effluent ratio of >
      15 to identify left-sided tumours, overall 66% of women were correctly
      categorized. CONCLUSIONS: Peripheral testosterone concentrations identified
      ovarian androgen-producing tumours, and venous sampling could correctly localize
      66% of these, suggesting a role for sampling when imaging studies are not
      revealing.

PMID- 18721193
TI  - LRP5 in premature adrenarche and in metabolic characteristics of prepubertal
      children.
AB  - OBJECTIVE: Premature adrenarche (PA) is associated with unfavourable metabolic
      characteristics. We hypothesized that genetic variation in low density
      lipoprotein (LDL) receptor-related protein 5 (LRP5), which is involved in Wnt
      signalling in the adrenal cortex and in cholesterol metabolism, plays a role in
      the pathogenesis of PA. DESIGN AND PATIENTS: We performed a cross-sectional
      association study in 73 Finnish children with PA and 97 age- and gender-matched
      healthy controls. MEASUREMENTS: LRP5 genotypes were determined by direct
      sequencing. Single-marker associations with clinical-metabolic characteristics,
      including adrenocortical function, glucose tolerance and lipid profile, were
      examined with age and gender as covariates. RESULTS: Nineteen single nucleotide
      polymorphisms (SNPs) in LRP5 were found in the 170 children. No significant
      differences in the genotype distributions were observed between the PA and
      control groups. SNPs A1330V and N740N were associated with higher serum
      dehydroepiandrosterone sulphate (DHEAS) levels in the control subjects (A/A vs.
      A/a; mean 0.8 vs. 1.4 micromol/l, P = 0.01). They were also associated with
      higher plasma levels of total (4.2 vs. 4.7 mmol/l, P = 0.02) and LDL cholesterol
      (2.4 vs. 2.9 mmol/l, P = 0.02) in the control group, as was SNP V1119V (P = 0.04
      and P = 0.03, respectively). SNPs F549F and V1119V were associated with higher
      systolic blood pressure (P = 0.04 and P = 0.02, respectively). There were no
      differences in the parameters of glucose metabolism between the genotype groups.
      CONCLUSIONS: Genetic variation in LRP5 did not predispose to PA but was
      associated with metabolic characteristics, especially lipid profile, in healthy
      prepubertal children.

PMID- 18721194
TI  - The IGF system and cytokine interactions and relationships with longitudinal
      growth in prepubertal patients with cystic fibrosis.
AB  - OBJECTIVE: Growth delay is a feature of patients with cystic fibrosis (CF). CF is
      a condition characterized by chronic inflammation that has been shown to modify
      the IGF system, which is essential for normal growth, and is related to pulmonary
      function in CF patients. We aimed to verify whether circulating levels of tumour
      necrosis factor (TNF)-alpha, interleukin (IL)-6, insulin and the IGF system were
      related and/or had relationships with linear growth in children with CF. DESIGN
      AND PATIENTS: Seventeen prepubertal CF patients (nine males and eight females) in
      a stable clinical condition were enrolled. Auxological parameters, pulmonary
      function and the Shwachman-Kulczycki (S-K) score were assessed, and serum samples
      were drawn at baseline and after 12 months. MEASUREMENTS: TNF-alpha, IL-6, IGF-I,
      IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and insulin were assayed using specific
      commercial kits. RESULTS: At baseline, TNF-alpha serum concentration was related
      to serum IGF-I concentration (R = 0.53), IGF-II bioactivity (IGF-II/IGFBP-3 molar
      ratio, R = +0.52) and insulin concentration (R = +0.63). Changes in serum IL-6
      and IGFBP-2 concentrations during the 12-month observation were positively
      correlated (R = +0.63). Changes in height standard deviation score (Ht SDS) were
      correlated with IGF-I serum concentrations at baseline (R =+0.67) and after 12
      months (R = +0.70), with IGF-I bioavailability and with IGFBP-1 serum
      concentrations (R = -0.88). Body mass index (BMI) SDS correlated with IGF
      bioavailability. CONCLUSIONS: This study showed a relationship between
      inflammatory status and the IGF system, and an effect of these interactions on
      longitudinal growth. Moreover, a role for insulin in growth was identified.
      Better control of inflammation and preservation of insulin secretion could
      benefit these patients.

PMID- 18721195
TI  - A 6-year investigation into types of dental trauma treated in a paediatric
      dentistry clinic in Eastern Anatolia region, Turkey.
AB  - The purpose of this study was to assess the frequency, the effective factors and
      the applied treatments for dental trauma among children aged 1-15 years from
      Eastern Anatolia in a 6-year period. The total frequency of trauma in this study
      was calculated as 4.9% during a 6-year period. The males were found to have more
      traumatic injury than females (P < 0.05). Also, the permanent teeth were more
      vulnerable to dental trauma than the primary teeth (P < 0.05). The highest
      frequency of traumas in the primary teeth was observed at the age of 5, whereas
      the rate for the permanent teeth was at the age of 10. The teeth mostly
      influenced by the traumas were the upper central incisors in both primary and
      permanent teeth. It was in October that traumas were mostly seen for the
      permanent teeth and in June for the primary teeth. The most frequent source of
      trauma in both genders and in both primary and permanent teeth were falls. The
      most common type of trauma in the primary teeth was lateral luxation, while it
      was enamel-dentin crown fracture in the permanent ones. Soft tissue injuries were
      observed in 143 of 653 dental traumatized children. The most common method of
      treatment was examination and follow up for the primary teeth, and only direct
      restoration for the permanent teeth without any endodontic treatment. 15% of the
      patients applied for treatment 1 year after injury event. Therefore, it was
      concluded that the patients, parents and teachers living in Eastern Anatolia
      should be informed about the necessity of early treatment of dental traumas and
      the consequence of a delay.

PMID- 18721196
TI  - Effect of root surface treatment with propolis and fluoride in delayed tooth
      replantation in rats.
AB  - Replantation is an acceptable option for treatment of an avulsed permanent tooth.
      Nevertheless, an extended extraoral period damages the periodontal ligament and
      results in external root resorption. The purpose of this study was to assess by
      histologic and histometric analysis, the influence of propolis 15% (natural
      resinous substance collected by Apis mellifera bees from various plants) and the
      fluoride solution used as root surface treatment on the healing process after
      delayed tooth replantation. Thirty Wistar (Rattus norvegicus albinus) rats were
      submitted to extraction of their upper right incisor. The teeth were maintained
      in a dry environment for 60 min. After this, the pulp was extirpated and the
      papilla, enamel organ and periodontal ligament were removed with scalpel. The
      teeth were divided into three experimental groups: Group I - teeth immersed in 20
      ml of physiologic saline; Group II - teeth immersed in 20 ml of 2% acidulated
      phosphate sodium fluoride; Group III - teeth immersed in 20 ml of 15% propolis.
      After 10 min of immersion in the solutions, the root canals were dried and filled
      with calcium hydroxide paste and the teeth were replanted. The animals were
      euthanized 60 days after replantation. The results showed that similar external
      root resorption was seen in the propolis and fluoride groups. Teeth treated with
      physiologic saline tended to have more inflammatory root resorption compared with
      those treated with fluoride or propolis. However, the comparative analysis did
      not reveal statistically significant differences (P > 0.05) between the treatment
      modalities when used for delayed tooth replantation.

PMID- 18721198
TI  - Prospective assessment of the efficacy of single dose versus traditional 3-day
      antimicrobial prophylaxis in 12-core transrectal prostate biopsy.
AB  - OBJECTIVES: To prospectively evaluate the efficacy of single dose antibiotic
      prophylaxis in 12-core transrectal ultrasonography (TRUS) guided prostate biopsy.
      METHODS: A total of 400 patients who underwent prostate biopsy with TRUS guidance
      were included. The patients were prospectively randomized in three groups
      regarding antibiotic prophylaxis. The first group (139 patients) received a
      single gram of intramuscular ceftriaxone, while the second group (131 patients)
      had a 3-day course of oral ciprofloxacin. The third group (130 patients) had
      single oral 500 mg of ciprofloxacin. All patients had urine cultures prior to
      biopsy and on the second day after biopsy. RESULTS: The study groups were
      compared in terms of the results of urine cultures and clinical parameters.
      Overall, only seven patients (1.8% of the cases) had positive urine cultures with
      no difference between these three groups. Additionally, no significant difference
      was observed regarding morbidity rates in all groups. Only eight patients (2%)
      developed major complications requiring hospitalization. There was no increase in
      the rate of infectious complications when the biopsy core numbers were increased
      up to 12. CONCLUSIONS: The current study suggests that a single oral dose of
      antimicrobial prophylaxis is reasonable in TRUS prostate biopsy even in the case
      of 12-core sampling.

PMID- 18721197
TI  - Inhibition of atopic dermatitis-like skin lesions by topical application of a
      novel ceramide derivative, K6PC-9p, in NC/Nga mice.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease that commonly
      begins in childhood. K6PC-9p (N-(Ethyl dihydrogenphosphate)-2-hexyl-3-oxo
      decanamide) is a synthetic ceramide derivative of PC-9S (N-Ethanol-2-mirystyl-3
      oxo-staramide), which was known to be effective in atopic patients. In this
      study, we examined the effect of topical application of K6PC-9p on skin
      inflammation and AD-like skin lesions in mouse models. K6PC-9p dose-dependently
      inhibited phorbol ester-induced increase in ear thickness in BALB/c mice.
      Moreover, topical application of K6PC-9p suppressed dust mite extract-induced AD
      like skin lesions in NC/Nga mice. Histopathological analysis revealed that both
      ear swelling and leucocyte infiltration were suppressed by K6PC-9p treatment.
      K6PC-9p also suppressed IL-4 and TNF-alpha expression in the ears and mast cell
      infiltration into the ears in NC/Nga mice. Further study demonstrated that K6PC
      9p inhibited ConA-induced IL-4 secretion and LPS-induced macrophage activation.
      Taken together, our results showed that topical application of K6PC-9p exerts
      beneficial effects in animal model of skin inflammation and AD, suggesting that
      K6PC-9p might be a promising topical agent for the treatment of inflammatory skin
      diseases.

PMID- 18721199
TI  - Efficacy of bacillus Calmette-Guerin in the treatment of superficial bladder
      cancer: the impact of previous intravesical treatment.
AB  - OBJECTIVE: To clinically evaluate the role of intravesical bacillus Calmette
      Guerin (BCG) in the management of superficial bladder cancer, focusing on dose,
      age, high grade/stage, and pretreatment episodes with other therapies in long
      term follow-up patients. METHODS: A total of 213 patients with superficial (Ta
      T1) transitional cell carcinoma of the bladder received 6-8 weekly instillations
      of 40, 60 or 80 mg of Tokyo strain BCG. Further 6-8 monthly applications were
      given in some cases. RESULTS: Recurrence-free and progression-free survival rates
      were compared with reference to dose, age, previous treatment, grade, stage, and
      high risk categories. Overall recurrence-free rates for 3, 5, and 10 years were
      70.8%, 67.1%, and 57.6%, with progression-free survival rates of 94.5%, 93.6%,
      90.6%, respectively. In univariate analyses, younger cases demonstrated higher
      recurrence-free survival rates, but without statistical significance (P =
      0.1229). Recurrence-free rates were significantly higher for cases without
      previous intravesical treatment (P = 0.0010). There was no significant BCG dose
      dependence. High grade and high stage patients were confirmed as having higher
      recurrence and progression rates. CONCLUSIONS: Intravesical instillation of BCG
      is the most effective in the long term when chosen as the initial prophylactic
      therapy for the prevention of recurrence in superficial bladder cancer.

PMID- 18721200
TI  - Do perineal exercises during pregnancy prevent the development of urinary
      incontinence? A systematic review.
AB  - OBJECTIVES: The aim of the current article was to conduct a systematic review of
      the performance of perineal exercises during pregnancy and their utility in the
      prevention of urinary incontinence. METHODS: Randomized controlled studies (RCT)
      of a low-risk obstetric population (primiparas or nulliparas) who had done
      perineal exercises only during pregnancy met the inclusion criteria. Articles
      published between 1966 and 2007 from periodicals indexed in the LILACS, SCIELO,
      PubMed/MEDLINE, SCIRUS and Cochrane Library databases were selected, using the
      following keywords: 'urinary incontinence', 'pregnancy', 'pelvic floor' and
      'exercise'. The Jadad scale was applied to assess the internal validity of the
      RCT and two meta-analysis: one of fixed effects and the other of random effects
      were carried out with data extracted from the RCT, using the Stata 9.2
      statistical software and adopting a significance level of 0.05. RESULTS: Four
      RCTs with high methodological quality, involving a total of 675 women were
      included. They indicated that perineal muscle exercise significantly reduced the
      development of urinary incontinence from 6 weeks to 3 months after delivery (odds
      ratio = 0.45; confidence interval: 0.3 to 0.66). However, when evaluating this
      effect during the 34th and 35th gestational week, a meta-analysis showed that the
      results were not significant (odds ratio = 0.13; confidence interval: 0.00 to
      3.77). CONCLUSION: Pelvic floor muscle exercises may be effective at reducing the
      development of postpartum urinary incontinence, despite clinical heterogeneity
      among the RCT.

PMID- 18721201
TI  - Salvage radiotherapy following radical prostatectomy.
AB  - Recurrent disease following radical prostatectomy will occur in approximately 20%
      of patients, for whom the therapeutic options include surveillance, salvage
      radiotherapy, or hormonal therapy. This review will focus on the evidence for
      salvage radiotherapy. Efficacy results of 30-50% have been reported from multiple
      retrospective series, with minimal morbidity. Unfortunately there are no
      randomized or prospective studies in this area. Results of salvage radiotherapy
      improve when given earlier, ideally with the serum prostate-specific antigen < 1
      ng/mL. Other positive prognosticators are positive margins at radical
      prostatectomy, longer prostate-specific antigen doubling times, lower radical
      prostatectomy Gleason scores, and the absence of lymph node metastases. Current
      standard dosage is 64 Gy or slightly higher, although the optimal dosage has yet
      to be defined with prospective randomized trials. Salvage radiotherapy can
      provide a durable response when given early, and patients with recurrent disease
      should be considered for treatment or enrolment in clinical trials.

PMID- 18721202
TI  - Epigenetic markers as promising prognosticators for bladder cancer.
AB  - Transitional cell carcinomas of the urinary bladder have diverse biological and
      functional characteristics. Surveillance strategies for bladder cancer recurrence
      have historically relied on the diagnostic combination of cystoscopy and urinary
      cytology. However, the accuracy of both tests depends on subjective and operator
      dependent interpretations of the visible findings. In contrast, promoter
      hypermethylation of CpG islands is strongly associated with tumor development and
      prognosis of bladder cancer. Detection of DNA methylation in voided urine may be
      feasible and more sensitive than conventional urine cytology. Ultimately, all
      types of urological cancers may be screened in urine using a candidate panel of
      hypermethylated genes. The epigenetic silencing of tumor suppressor genes is
      interest from a clinical point of view because it is possible to reverse
      epigenetic changes and restore gene function to a cell. Methylation markers might
      therefore be more useful than conventional molecular markers for the treatment
      and prevention of bladder cancer.

PMID- 18721203
TI  - Endogenous oxalogenesis after acute intravenous loading with ethylene glycol or
      glycine in rats receiving standard and vitamin B6-deficient diets.
AB  - OBJECTIVES: The effect on endogenous oxalate synthesis of acute intravenous
      loading with ethylene glycol or glycine was investigated in rats on a standard or
      a vitamin B6-deficient diet. METHODS: Twenty-four male Wistar rats weighing
      approximately 180 g were randomly divided into ethylene glycol and glycine groups
      of 12 animals each. These groups were further divided into two subgroups of six
      animals each that were fed either a standard or a vitamin B6-deficient diet for 3
      weeks. Animals of these two subgroups received an intravenous infusion of 20 mg
      (322.22 micromol) of ethylene glycol or 100 mg (1332.09 micromol) of glycine,
      respectively. Urine samples were collected just before intravenous infusion of
      each substance and at hourly intervals until 5 h after receiving the infusion.
      Urinary oxalate, glycolate, and citrate levels were measured by capillary
      electrophoresis. RESULTS: Urinary oxalate and glycolate excretion was
      significantly increased after ethylene glycol administration. Significant
      differences between the control and vitamin B6-deficient groups were found. In
      contrast, there were only small changes of oxalate and glycolate excretion after
      glycine administration. Recovery of the given dose of ethylene glycol as oxalate
      in 5-h urine was 0.31% and 7.15% in the control and vitamin B6-deficient groups,
      respectively, whereas recovery of glycolate was 0.68% and 7.22%, respectively.
      CONCLUSIONS: Ethylene glycol loading has a significant effect on urinary oxalate
      excretion in both normal and vitamin B6-deficient rats, whereas glycine loading
      only has a small effect. Oxalate and glycolate excretion after ethylene glycol
      loading were respectively 23-fold and 11-fold higher in vitamin B6-deficient rats
      than in controls.

PMID- 18721204
TI  - Lymphovascular invasion is an independent predictor of prostate-specific antigen
      failure after radical prostatectomy in patients with pT3aN0 prostate cancer.
AB  - OBJECTIVES: To investigate the association of lymphovascular invasion (LVI) in
      radical prostatectomy (RP) specimens with prostate-specific antigen (PSA) failure
      in patients with pT3aN0 prostate cancer (PCA). METHODS: We retrospectively
      reviewed the clinical records of 94 patients with pT3aN0 PCA treated with RP
      alone. All of the 94 patients were prospectively observed without any treatment
      until PSA failure was confirmed. We investigated the association of LVI with the
      adverse pathological findings in RP specimens and the PSA failure-free survival
      rate. The Cox proportional hazard model was used to elucidate predictors of PSA
      failure. RESULTS: Median follow up was 47.4 months (quartile range 9.1 to 146.8).
      LVI was found in 26 (27.7%) of the 94 patients. In a multivariate analysis, PSA
      (P = 0.0054) and LVI (P = 0.015) were significant and independent predictors of
      PSA failure. Stratifying patients into four risk groups by LVI status and PSA
      level, the PSA failure-free survival rate in patients with negative LVI and PSA <
      or =10 ng/mL was significantly better than any other groups (positive LVI and/or
      PSA >10 ng/mL). CONCLUSIONS: Adjuvant therapy would not be indicated to patients
      with pT3aN0 PCA with negative LVI and PSA < or =10 ng/mL.

PMID- 18721205
TI  - The association between metabolic syndrome and prostate-specific antigen levels.
AB  - OBJECTIVES: Prostate-specific antigen (PSA) levels are affected by many factors.
      Metabolic syndrome (MS) is a common metabolic disorder related to the increasing
      prevalence of obesity. The relationship between MS and PSA is currently unknown,
      however. The aim of this study was to examine whether PSA levels were affected by
      MS. METHODS: We evaluated the association between MS and PSA in a group of 2007
      men (aged 30 to 79 years) without prostate cancer who received a general health
      checkup. Men with abnormal digital rectal examination findings or PSA values
      higher than 3.0 ng/mL were considered abnormal and excluded from the study. MS
      was defined according to the modified National Cholesterol Education Program
      Third Adult Treatment Panel guidelines. Eligible men were classified according to
      the number of each component and the presence or absence of MS. RESULTS: PSA
      levels, as a whole, were inversely correlated with MS (P = 0.043). An increased
      number of MS components was significantly associated with linear decreasing
      trends of PSA levels (P-trend < 0.001). When a multivariate analysis was
      performed with age and each MS, age (P < 0.001), abdominal obesity (P = 0.001),
      and an impaired fasting glucose level (P = 0.047) were strongly associated with
      PSA levels. CONCLUSIONS: MS is associated with decreased PSA levels. When
      determining whether to perform prostate biopsy as part of early prostate cancer
      detection, MS should be considered as a factor associated with reduced PSA in men
      presenting with marginal PSA levels.

PMID- 18721206
TI  - Ejaculatory dysfunction caused by the new alpha1-blocker silodosin: A preliminary
      study to analyze human ejaculation using color Doppler ultrasonography.
AB  - OBJECTIVES: In order to clinically investigate the mechanism of ejaculatory
      dysfunction attributable to the alpha1-blocker silodosin, a real-time observation
      of ejaculation by healthy males was performed. METHODS: Following intake of
      silodosin, a newly developed selective alpha1-blocker for benign prostatic
      hypertrophy, ejaculation was dynamically observed using color Doppler ultrasound
      in three healthy males. Normal ejaculation was also investigated in the same
      manner. RESULTS: With silodosin intake, no antegrade ejaculation was observed in
      cases 1 or 2. In case 1, seminal fluid slowly but continuously flowed out from
      the seminal vesicles into the bladder. In case 2, only a small amount of seminal
      fluid flowed into the bladder during the ejaculatory sensation. In case 3,
      ejection of a small amount of semen from the external urethral orifice was
      observed and inflow of a small amount of seminal fluid into the bladder was also
      captured. Without silodosin intake, all three subjects exhibited antegrade
      ejaculation. CONCLUSIONS: The mechanism of ejaculatory dysfunction is intricately
      related to retrograde ejaculation (retrograde inflow of seminal fluid),
      insufficient contraction of the seminal vesicles, and insufficient rhythmic
      contraction of the muscles of the pelvic floor.

PMID- 18721207
TI  - Does a previous end-to-end urethroplasty alter the results of redo end-to-end
      urethroplasty in patients with traumatic posterior urethral strictures?
AB  - OBJECTIVES: To evaluate the success rate of redo anastomotic urethroplasty and to
      compare it with primary anastomotic urethroplasty. METHODS: We compared 52
      patients with post-traumatic posterior urethral strictures (group 1, mean age
      24.6 years, range 10-62) who had undergone redo urethroplasty with 66 patients
      (group 2, mean age 22.6, range 6-71) who had undergone primary anastomotic
      urethroplasty. Mean stricture length was 2.0 cm (1-4.5) and 2.5 cm (1.5-6),
      respectively. All of the patients in group 1 had a stricture located at the
      bulboprostatic anastomotic site. In group 2, 43 (65.2%) had a bulbomembranous
      stricture and 23 (34.8%) had a prostatomembranous stricture. RESULTS: Mean
      operative time was 140 (100-240) and 90 min (75-200) in group 1 and 2,
      respectively. Mean blood loss was 180 (80-900) and 125 mL (50-700), respectively.
      Mean hospital stay was comparable (6.6 days vs 5.5 days) between the two groups.
      Mean follow up was 54 months (10-144) for group 1 and 62 months (12-122) for
      group 2. Corporal separation, inferior pubectomy, a transpubic approach and
      urethral rerouting were required in 22 (42.3%) and 12 (18.2%), 7 (13.5%) and 3
      (4.5%), 12 (23%) and 5 (7.6%), 2 (3.8%) and nil patients in group 1 and 2,
      respectively. An excellent or acceptable outcome was achieved in 42 (80.8%) and
      57 (86.4%), 8 (15.4%) and 7 (10.6%) patients, respectively. Two patients in each
      group failed. CONCLUSIONS: Previously failed end-to-end urethroplasty does not
      alter the success rate of redo end-to-end urethroplasty.

PMID- 18721208
TI  - The effectiveness of tamsulosin in treating women with voiding difficulty.
AB  - OBJECTIVES: To prospectively evaluate the effectiveness of tamsulosin in treating
      women with voiding difficulty. METHODS: Female patients presenting chronic,
      bothersome voiding symptoms, combined with subnormal uroflow were treated with
      0.2 mg tamsulosin daily for six weeks. Outcome analyses included the
      International Prostate Symptom Score and uroflowmetry with post-void residual
      urine. Patients achieving a 50% or greater reduction in their voiding symptom
      score, combined with a 30% or greater increment in their maximal flow rate were
      regarded as having a good therapeutic response. Subgroup analysis was performed
      in patients classified as having bladder outlet obstruction, or detrusor
      underactivity based on pressure-flow study, excluding those with indwelling
      catheterization or intermittent self-catheterization as well as those with
      anatomic obstruction. RESULTS: Ninety-seven patients met the study inclusion
      criteria and were enrolled. Significant improvements in voiding symptom score,
      storage symptom score, maximal flow rate, post-void residual urine and voiding
      efficiency were observed in all patients while on tamsulosin. A good therapeutic
      response was observed in 35.1% of patients. Of these, 33 were classified as
      having bladder outlet obstruction and 52 had detrusor underactivity. Although
      both groups experienced significant reduction in their voiding symptom scores,
      patients with bladder outlet obstruction were more likely to achieve a reduction
      of their voiding symptom score. The magnitude of improvement in uroflow
      parameters as well as the proportion of patients achieving a good therapeutic
      response (39.4% for bladder outlet obstruction vs 32.7% for detrusor
      underactivity, P = 0.69) were similar between the two groups. Adverse events were
      mild and tolerable. CONCLUSIONS: Tamsulosin has beneficial effects in a
      significant proportion of women with voiding difficulty.

PMID- 18721209
TI  - NF-kappaB activation in renal tubular epithelial cells by oxalate stimulation.
AB  - OBJECTIVES: The transcription factor nuclear factor-kappaB (NF-kappaB) is
      involved in inflammatory and immune responses through the induction of various
      cytokines and growth factors. Recently, the coordinated action of NF-kappaB and
      activator protein-1 was reported in osteopontin (OPN) expression. In the present
      study, we demonstrated that oxalate induces OPN expression by activating NF
      kappaB in renal tubular cells. Furthermore, we investigated the inhibitory effect
      of N-acetyl-L-cysteine (NAC) on NF-kappaB activation in the human renal tubular
      cell line. METHODS: All of the experiments were carried out using human kidney-2
      cells, which are human proximal tubular epithelial cells immortalized by
      transduction with the human papillomavirus 16E6/E7 gene. The time-dependent
      extraction of total protein was performed after the uptake of 0.5 mM oxalate by
      the cells. The NF-kappaB activation and OPN expression were examined by western
      blotting and immunocytochemistry. RESULTS: As a result of oxalate stimulation,
      the amount of p65 subunit in the nucleus increased significantly (P < 0.05), and
      NAC significantly inhibited the translocation of p65 into the nucleus (P < 0.05).
      CONCLUSION: These observations indicate that NAC can be used as a drug to prevent
      stone formation.

PMID- 18721210
TI  - Androgens upregulate aquaporin 9 expression in the prostate.
AB  - OBJECTIVES: Aquaporins (AQP) function as selective pores allowing water, glycerol
      and other small solutes to pass through the cell membrane. We previously reported
      that AQP are expressed in the prostates of both humans and rats. The present
      study investigated the androgen-dependent expression of AQP9 in the prostate in
      vivo and in vitro. METHODS: Rat ventral prostate tissue specimens and a normal
      human prostatic epithelial cell line (PNT2) were used. AQP9 messenger ribonucleic
      acid (mRNA) and protein expression were examined using real-time polymerase chain
      reaction, Western blotting and immunohistochemical methods. Androgen modulation
      was achieved by surgical castration, treatment with testosterone propionate (5
      microg/g bodyweight) or bicalutamide (20 microg/g bodyweight), and the
      ribonucleic acid interference (RNAi) method of the androgen receptor (AR). The
      synthetic small interfering RNA was transfected into PNT2 at a concentration of
      10 nM, and the RNAi effect was evaluated using a Western blotting analysis.
      RESULTS: AQP9 mRNA and protein were expressed in the rat prostate. Surgical
      castration or bicalutamide treatment significantly decreased their expression. In
      addition, the treatment with testosterone propionate after castration restored
      the expression to the level of the controls. An RNAi experiment in PNT2 also
      decreased the expression. CONCLUSIONS: AQP9 expression in the prostate is
      controlled by androgens.

PMID- 18721211
TI  - Di-isostearyl malate and macademia nut oil in lipstick caused cheilitis.

PMID- 18721213
TI  - A study on plucked hair as a substrate for direct immunofluorescence in pemphigus
      vulgaris.
AB  - BACKGROUND: It has recently been demonstrated in a study on 15 patients that
      plucked hair can be used as a substrate for direct immunofluorescence (DIF) in
      pemphigus. OBJECTIVE: Our aim was to assess the sensitivity of DIF on plucked
      hairs in pemphigus vulgaris (PV) patients with positive DIF of oral mucosa.
      METHODS: One hundred and ten new PV patients were enrolled in the study. They all
      showed the typical clinical and histological findings as well as positive DIF of
      the oral mucosa, diagnostic for PV. Approximately 30 hairs were obtained in the
      same way as for the trichogram. The hairs with their outer root sheaths (ORS)
      were processed for DIF in order to detect immunoglobulin G and C3. RESULTS:
      Immunodeposits favouring PV were demonstrated in the ORS of 100 cases showing a
      sensitivity of 91%. CONCLUSION: Regarding the relatively high sensitivity of DIF
      on plucked hair in PV patients with positive oral mucosal DIF in our study, it
      seems that hair plucking is a suitable alternative to the more invasive
      techniques of skin or mucosal biopsy for obtaining specimens for DIF in PV.

PMID- 18721214
TI  - Dramatic improvement of atopic  keratoconjunctivitis after topical  treatment
      with tacrolimus  ointment restricted to the eyelids.

PMID- 18721215
TI  - Immediate allergy, drug-induced  eruption, by entecavir.

PMID- 18721216
TI  - Improvement of idiopathic  acanthosis nigricans with a triple  combination
      depigmenting  cream.

PMID- 18721217
TI  - Secondary syphilis mimicking  pemphigus vulgaris.

PMID- 18721218
TI  - Successful treatment of recalcitrant relapsing polychondritis with monoclonal
      antibodies.

PMID- 18721219
TI  - Pemphigus foliaceus associated with oesophageal cancer.

PMID- 18721220
TI  - Reversible ageusia as an adverse effect of hydroxychloroquine treatment.

PMID- 18721221
TI  - Subsequent fracture in nursing home residents with a hip fracture: a competing
      risks approach.
AB  - OBJECTIVES: To determine the incidence and predictors of subsequent fracture in
      nursing home residents with a hip fracture, accounting for the competing risk of
      death. DESIGN: Dynamic cohort study. SETTING: Hebrew Rehabilitation Center, a 725
      bed, long-term care facility in Boston, Massachusetts. PARTICIPANTS: Long-term
      care residents with a surgically repaired hip fracture (1999-2006) followed
      through June 30, 2007, for the occurrence of subsequent fracture at any skeletal
      site. MEASUREMENTS: Information on age, sex, anatomic location, type of repair,
      body mass index (BMI), comorbidities, functional status, cognitive status, and
      medication use were evaluated as potential risk factors for subsequent fracture.
      RESULTS: The study included 184 residents with a baseline hip fracture. Thirty
      nine residents (7 men, 32 women) experienced a subsequent fracture over a median
      follow-up of 1.1 years. After the baseline hip fracture, 6% of residents
      experienced a subsequent fracture within 6 months, 12% within 1 year, and 21%
      within 5 years. In addition, 23% of residents died within 6 months, 31% within 1
      year, and 60% within 5 years. High functional status was associated with a five
      times greater risk of subsequent fracture (high vs low functional status, hazard
      ratio=5.10, P<.005). Age, sex, BMI, comorbidities, cognitive status, and
      medication use were not associated with subsequent fracture. CONCLUSION: Hip
      fractures are a sentinel event in nursing home residents, with a high incidence
      of subsequent fracture and death occurring within 1 year. Identification of
      prefracture characteristics and postfracture complications associated with
      mortality should help guide secondary prevention efforts in nursing home
      residents.

PMID- 18721222
TI  - A senior center-based pilot trial of the effect of lifestyle intervention on
      blood pressure in minority elderly people with hypertension.
AB  - OBJECTIVES: To test the feasibility, acceptability, and effect of a senior center
      based behavioral counseling lifestyle intervention on systolic blood pressure
      (BP). DESIGN: A pre-post design pilot trial of behavioral counseling for
      therapeutic lifestyle changes in minority elderly people with hypertension.
      Participants completed baseline visit, Visit 1 (approximately 6 weeks
      postbaseline), and a final study Visit 2 (approximately 14 weeks postbaseline)
      within 4 months. SETTING: The study took place in six community-based senior
      centers in New York City with 65 seniors (mean age 72.29+/-6.92; 53.8% female;
      84.6% African American). PARTICIPANTS: Sixty-five minority elderly people.
      INTERVENTION: Six weekly and two monthly "booster" group sessions on lifestyle
      changes to improve BP (e.g., diet, exercise, adherence to prescribed
      antihypertensive medications). MEASUREMENTS: Primary outcome was systolic BP
      (SBP) measured using an automated BP monitor. Secondary outcomes were diastolic
      BP (DBP), physical activity, diet, and adherence to prescribed antihypertensive
      medications. RESULTS: There was a significant reduction in average SBP of 13.0+/
      21.1 mmHg for the intervention group (t(25)=3.14, P=.004) and a nonsignificant
      reduction in mean SBP of 10.6+/-30.0 mmHg for the waitlist control group
      (t(29)=1.95, P=.06). For the intervention group, adherence improved 26%
      (t(23)=2.31, P=.03), and vegetable intake improved 23% (t(25)=2.29, P=.03).
      CONCLUSION: This senior center-based lifestyle intervention was associated with a
      significant reduction in SBP and adherence to prescribed antihypertensive
      medications and diet in the intervention group. Participant retention and group
      attendance rates suggest that implementing a group-counseling intervention in
      senior centers is feasible.

PMID- 18721223
TI  - Development and implementation of an objective structured clinical examination to
      provide formative feedback on communication and interpersonal skills in geriatric
      training.
AB  - Teaching and assessment of communication and interpersonal skills, one of the
      American Council for Graduate Medical Education-designated core competencies, is
      an important but difficult task in the training of physicians. Assessment of
      trainees offers an opportunity to provide explicit feedback on their skills and
      encourages learning. This article describes a pilot study in which clinician
      educators affiliated with the geriatrics training programs at Beth Israel
      Deaconess Medical Center and Boston University Medical Center designed and
      piloted a novel Objective Structured Clinical Examination (OSCE) to assess the
      communication and interpersonal skills of medical, dental, and geriatric
      psychiatry fellows. The OSCE consisted of three stations where geriatricians and
      standardized patients evaluated candidates using specifically designed checklists
      and an abbreviated version of the Master Interview Rating Scale. Communication
      skills were assessed through performance of specific "real life" clinical tasks,
      such as obtaining a medical history, explaining a diagnosis and prognosis, giving
      therapeutic instructions, and counseling. Interpersonal skills were assessed
      through the effect of the communication between doctor and standardized patient
      on fostering trust, relieving anxiety, and establishing a therapeutic
      relationship. This pilot study demonstrated that the OSCE format of assessment
      provides a valid means of evaluating the communication and interpersonal skills
      of interdisciplinary geriatric trainees and provides a valuable forum for
      formative assessment and feedback. Given that geriatricians and non geriatricians
      involved in elder care both need communication and interpersonal skills, this
      novel OSCE can be used for assessment of these skills in trainees in diverse
      healthcare subspecialties.

PMID- 18721224
TI  - The influence of age on changes in health-related quality of life over three
      years in a cohort undergoing hemodialysis.
AB  - OBJECTIVES: To assess the extent to which persons aged 70 and older undergoing
      hemodialysis (HD) had greater changes in health-related quality of life (HRQOL)
      over 3 years than younger patients undergoing HD. DESIGN: Longitudinal. SETTING:
      The Hemodialysis Study (HEMO Study) was a randomized, clinical trial of the
      effects of HD dose and membrane flux on mortality and morbidity in patients
      undergoing chronic dialysis. PARTICIPANTS: Secondary analysis of the HEMO Study.
      MEASUREMENTS: Participants completed the Index of Well-Being (IWB) and the Kidney
      Disease Quality of Life-Long Form (KDQOL-LF), which also includes the Medical
      Outcomes Study 36-item Short Form Questionnaire (SF-36) annually. Changes in
      subjects those aged 70 and older were compared with changes in subjects aged 55
      to 69 and 18 to 54. RESULTS: At baseline, 1,813 (98%) of HEMO participants
      completed HRQOL surveys. Their mean age was 58, 56% were female, 64% were black,
      and mean duration of dialysis was 3.8 years. In subjects with HRQOL data at the
      first three annual assessments, there were no substantial mean declines in the SF
      36 Physical or Mental Component Summary scales over 3 years. In models
      incorporating effects of attrition, the differences in average change over 3
      years between patients undergoing HD aged 70 and older and the younger cohorts
      were small in magnitude. There were high rates of adverse HRQOL events in all age
      groups and significantly higher composite event rates of death or clinically
      significant decline in HRQOL over 3 years was found in subjects aged 70 and
      older. CONCLUSION: Although HRQOL was impaired in the population undergoing HD,
      HRQOL scores at baseline reflect a better-preserved multidimensional quality of
      life in respondents in the HEMO Study aged 70 and older than in younger patients
      undergoing HD. There was no substantial relationship between age and average
      decline in HRQOL score over 3 years in participants in the HEMO Study.

PMID- 18721226
TI  - Induction of a protective immune response against swine Chlamydophila abortus
      infection in mice following co-vaccination of omp-1 DNA with recombinant MOMP.
AB  - Chlamydophila abortus is the causative agent of abortion in pigs and pregnant
      women. Seroconversion rates were arranged from 11% to 80% in piglets and sows in
      China. These very high rates illustrate the scale of the problem in China and
      highlight the urgent need for the development of a C. abortus vaccine. An
      efficacious anti-chlamydial vaccine should induce not only strong mucosal and
      systemic T-helper type 1 (Th1) immune response but also give a humoral response
      that enhances Th1 activation following infection. In order to evaluate an active
      immune response of a combination of the major outer membrane protein (MOMP) DNA-
      and protein-based vaccines, 54 BALB/c mice were randomly assigned to six groups
      and inoculated intramuscularly with: (i) 100 microg pcDNA::MOMP, (ii) 10 microg r
      MOMP, (iii) primed with 100 microg pcDNA::MOMP and boosted with 10 microg r-MOMP,
      (iv) primed-boosted with a combination of pcDNA::MOMP and r-MOMP simultaneously,
      (v) live-attenuated 1B vaccine, (vi) 100 microg pcDNA3.1 vector. All animals were
      vaccinated two times at 14 days intervals. Results showed that mice given DNA and
      r-MOMP induced higher antibody levels, higher T cells proliferation and an
      elevated level of chlamydial clearance in spleen, which was equivalent to the
      clearance of 1B vaccine. Mice administrated the DNA-primed/MOMP-boosted approach
      elicited moderate antibody levels, less T-lymphocyte proliferation and lower
      chlamydial clearance as compared with 1B vaccine. Co-immunization with DNA- and r
      MOMP vaccine may provide novel ways for active immunization strategy against
      swine C. abortus.

PMID- 18721227
TI  - The first finding of Echinococcus multilocularis in dogs in Slovakia: an emerging
      risk for spreading of infection.
AB  - Alveolar echinococcosis, caused by the metacestode Echinococcus multilocularis,
      is a zoonosis of public health significance. Apart from red foxes, other
      carnivore species can also serve as definitive hosts of this parasite. This study
      aimed to determine the occurrence of E. multilocularis in dogs in the Slovak
      Republic and identify risk factors for acquiring the infection. Out of 289 dogs
      examined, E. multilocularis was detected in eight samples (2.8%). Positive
      results were observed in shepherd dogs (12.5%), guard dogs (7.1%), hunting dogs
      (2.4%) and in one dog with unknown usage (2.5%). Catching rodents and feeding
      with raw viscera were confirmed to be the most important risk factors for E.
      multilocularis infection. On the contrary, the way of dog use, frequency of going
      to the rural areas, the age and gender of animals seem not to be risk factors for
      infection. No significant association was observed between the positivity of dogs
      coming from high endemic or non-endemic regions. This is the first report of E.
      multilocularis in dogs in the Slovak Republic that confirms substantial
      contribution of dogs to the transmission of the tapeworm in this territory and
      urges the necessity of prophylactic measures for dog owners.

PMID- 18721229
TI  - A study of proliferative markers and tumor suppressor gene proteins in different
      grades of ependymomas.
AB  - Ependymomas are CNS tumors that originate from the spinal canal and walls of the
      ventricular system. Considerable controversy continues to exist with regard to
      their prognostic factors; age and extent of resection are the only statistically
      significant prognostic factors yet identified. The authors report a retrospective
      study of a homogenous population of 119 patients harbouring ependymomas between
      1991 and 2002. All clinico-radiological and follow-up data were analyzed and a
      pathologic review was performed by two pathologists. Immunohistochemical staining
      for MIB-1, Topo IIalpha, p53 and MDM2 was performed. Histopathologic grades show
      relationship with MIB1 and Topo IIalpha labelling indices and cut-off values of
      5% can differentiate between anaplastic and lower grades. p53 and MDM2 proteins
      expression are not common in ependymomas; however, they are seen in higher grades
      only and may be involved in the tumor progression.

PMID- 18721230
TI  - Diagnostic pitfall: optic neuritis mimicking optic nerve glioma.
AB  - We report a case of optic neuritis with enlargement of the optic nerve on MRI.
      This neuroradiological finding is most commonly seen in tumours of the optic
      nerve and led together with an inconclusive intraoperative frozen section to an
      incorrect tentative diagnosis of optic nerve glioma which fatally resulted in the
      resection of the optic nerve.

PMID- 18721231
TI  - A critical review of the cannabinoid receptor as a drug target for obesity
      management.
AB  - The discovery of cannabinoids, with the well-known stimulatory effect of Cannabis
      sativa on appetite, has offered a new drug target for obesity treatment.
      Cannabinoids act on two different receptors: CB1 receptors which are sited in the
      brain and many peripheral tissues, and CB2 receptors which are primarily found in
      immune system cells. Cannabinoid receptor antagonists act centrally by blocking
      CB1 receptors, thereby reducing food intake. Moreover, they probably also act
      peripherally by increasing thermogenesis and therefore energy expenditure, as has
      been suggested by animal experiments. Despite these promising mechanisms of
      action, recent clinical studies examining the effect of the two CB1 receptor
      antagonists rimonabant and taranabant showed that the attained weight loss did
      not exceed that attained with other currently approved anti-obesity medications.
      Moreover, potentially severe psychiatric adverse effects limit their clinical
      use. As several new CB1 receptor antagonists are presently undergoing
      development, it remains to be elucidated to what extent they differ in terms of
      efficacy and safety. This review primarily discusses how close cannabinoid
      receptor antagonists are to the ideal anti-obesity drug, with respect to their
      mechanisms of action, clinical effectiveness and safety.

PMID- 18721228
TI  - SreA-mediated iron regulation in Aspergillus fumigatus.
AB  - Aspergillus fumigatus, the most common airborne fungal pathogen of humans,
      employs two high-affinity iron uptake systems: iron uptake mediated by the
      extracellular siderophore triacetylfusarinine C and reductive iron assimilation.
      Furthermore, A. fumigatus utilizes two intracellular siderophores, ferricrocin
      and hydroxyferricrocin, to store iron. Siderophore biosynthesis, which is
      essential for virulence, is repressed by iron. Here we show that this control is
      mediated by the GATA factor SreA. During iron-replete conditions, SreA deficiency
      partially derepressed synthesis of triacetylfusarinine C and uptake of iron
      resulting in increased cellular accumulation of both iron and ferricrocin. Genome
      wide DNA microarray analysis identified 49 genes that are repressed by iron in an
      SreA-dependent manner. This gene set, termed SreA regulon, includes all known
      genes involved in iron acquisition, putative novel siderophore biosynthetic
      genes, and also genes not directly linked to iron metabolism. SreA deficiency
      also caused upregulation of iron-dependent and antioxidative pathways, probably
      due to the increased iron content and iron-mediated oxidative stress.
      Consistently, the sreA disruption mutant displayed increased sensitivity to iron,
      menadion and phleomycin but retained wild-type virulence in a mouse model. As all
      detrimental effects of sreA disruption are restricted to iron-replete conditions
      these data underscore that A. fumigatus faces iron-depleted conditions during
      infection.

PMID- 18721232
TI  - Stoma obstruction after laparoscopic adjustable gastric banding for morbid
      obesity: report of two cases and treatment options.
AB  - Laparoscopic adjustable gastric band is one of the surgical options available for
      morbid obesity in the current century. Its popularity is gained by its proven
      efficacy with a reported low incidence of the intraoperative as well as the
      postoperative complications. Stomal obstruction post-laparoscopic adjustable
      gastric band (LAGB) has been under reported in the English literature. We report
      this complication in two patients and discuss two different simple modalities of
      treatment. Post-LAGB complications are numerous, dealing with their complications
      have a steeping curve. Educating the patients postoperatively in regard to food
      ingestion manner is a must and should prevent such complication.

PMID- 18721233
TI  - Expanding the genetic spectrum of pigmentation.

PMID- 18721234
TI  - Treatment of eosinophilic esophagitis: overview, current limitations, and future
      direction.
AB  - Eosinophilic esophagitis (EE) is an increasingly recognized syndrome presenting
      with upper gastrointestinal (UGI) symptoms in association with hypereosinophilia
      (>15 eosinophils/HPF) on esophageal mucosal biopsies. The pathogenesis is
      unknown, but the candidate etiologies include food and aeroallergen
      hypersensitivity and an unusual presentation of gastroesophageal reflux disease.
      This review will highlight the treatments of EE in children and adults. Current
      treatments are controversial, few data are available in adults, and long-term
      studies are almost nonexistent. We outline the limitations in the current studies
      and suggest seven major issues in the study design that must be addressed in
      future drug trials.

PMID- 18721239
TI  - Early versus delayed feeding after placement of a percutaneous endoscopic
      gastrostomy: a meta-analysis.
AB  - BACKGROUND: Traditionally, tube feedings have been delayed after percutaneous
      endoscopic gastrostomy (PEG) placement to the next day and up to 24 h
      postprocedure. However, results from various randomized controlled trials (RCTs)
      indicate earlier feeding may be an option. We conducted a meta-analysis to
      analyze the effect of early feedings (< or = 4 h) after PEG placement. METHODS:
      Multiple databases were searched (November 2007). Only RCTs on adult subjects
      that compared early (< or = 4 h) versus delayed or next-day feedings after PEG
      placement were included. Meta-analyses for the effect of early and delayed
      feedings were analyzed by calculating pooled estimates of complications, death <
      or = 72 h, and significant increases in postprocedural gastric residual volume
      during day 1. RESULTS: Six studies (N = 467) met the inclusion criteria. No
      statistically significant differences were noted between early (< or = 4 h) and
      delayed or next-day feedings for patient complications (OR 0.86, 95% CI 0.47
      1.58, P = 0.63) or death in < or = 72 h (OR 0.56, 95% CI 0.18-1.74, P = 0.31). A
      statistically significant increase in gastric residual volumes during day 1 was
      noted (OR 1.80, 95% CI 1.02-3.19, P = 0.04). CONCLUSIONS: Early feeding < or = 4
      h after PEG placement may represent a safe alternative to delayed or next-day
      feedings. Although an increase in significant gastric residual volumes at day 1
      was noted, overall complications were not affected.

PMID- 18721240
TI  - The prevalence of diarrhea and its association with drug use in elderly
      outpatients: a multicenter study.
AB  - OBJECTIVES: To evaluate the prevalence of diarrhea and its association with drug
      use in elderly outpatients. METHODS: The study was carried out by 133 general
      practitioners (GPs) who referred to 24 geriatric units in Italy. The demographic
      data, disability, gastrointestinal symptoms, and current medications were
      evaluated using a structured interview, including the evaluation of the
      activities of daily living (ADL), the instrumental activities of daily living
      (IADL), and the gastrointestinal symptoms rating scale (GSRS). RESULTS: The study
      included 5,387 elderly subjects who regularly completed the structured interview.
      In total, 488 patients (9.1% of the whole population, 210 men and 278 women, mean
      age 75.6 +/- 6.2 yr, range 65-100 yr) reported diarrhea, that is, items 11 and 12
      of the GSRS, during the 7-day period before the interview. The prevalence of
      diarrhea significantly increased with older age (P = 0.025), the severity of ADL
      (P < 0.0001) and IADL disability (P < 0.0001), and the number of drugs taken (P =
      0.0002). A multivariate analysis demonstrated that the presence of diarrhea was
      significantly associated with the use of antibiotics (odds ratio [OR] 4.58, 95%
      confidence interval [CI] 1.95-10.73), proton pump inhibitors (OR 2.97, 95% CI
      2.03-4.35), allopurinol (OR 2.19, 95% CI 1.26-3.81), psycholeptics (OR 1.82, 95%
      CI 1.26-2.61), selective serotonin reuptake inhibitors (OR 1.71, 95% CI 1.01
      2.89), and angiotensin II receptor blockers (OR 1.46, 95% CI 1.08-1.99), also
      accounting for sex, age, and the use of antidiarrheal agents and drugs for
      functional gastrointestinal disorders. CONCLUSION: Diarrhea is a common problem
      in elderly outpatients. Its prevalence increases with old age, the severity of
      disability, and the number of drugs. Monitoring the presence of diarrhea and its
      complications in elderly patients who need treatments with drugs significantly
      associated with diarrhea may be clinically useful.

PMID- 18721241
TI  - Changes in mood states and biomarkers during peginterferon and ribavirin
      treatment of chronic hepatitis C.
AB  - OBJECTIVE: Depression is a frequent side effect of interferon therapy in patients
      with chronic hepatitis C (CHC). The aim of this study was to identify baseline
      and on-treatment predictors of depression in CHC patients receiving peginterferon
      and ribavirin. METHODS: In total, 201 prior nonresponders with advanced fibrosis
      were treated with peginterferon alfa-2a and ribavirin for 24 wk in the Hepatitis
      C Antiviral Long-term Treatment against Cirrhosis trial. Of these, 74 continued
      on antiviral therapy through week 48. Mood states were assessed with the Beck
      Depression Inventory II and the Composite International Diagnostic Interview.
      Plasma cortisol and whole blood serotonin levels were measured in 101 subjects at
      weeks 0, 4, 24, 48, and 72. RESULTS: The incidence of interferon-induced
      depression was 23% and 42% at weeks 24 and 48, respectively. Although 22% of
      patients had baseline depression, the absence of a week 20 virological response
      was the only independent predictor of interferon-induced depression at week 24 (P
      = 0.0009). Plasma cortisol levels did not change during treatment nor correlate
      with depression. In contrast, whole blood serotonin/platelet levels significantly
      decreased during treatment, but did not correlate with interferon-induced
      depression through week 24 (P = 0.35), nor through week 48 (P = 0.51).
      CONCLUSION: Depression during peginterferon and ribavirin therapy was associated
      with a lower antiviral response. The significant reduction in whole blood
      serotonin levels over time suggest that further studies of the serotonergic
      pathway are warranted to identify the mediators of interferon-induced depression.

PMID- 18721242
TI  - A new scoring system for prognostic stratification of patients with alcoholic
      hepatitis.
AB  - OBJECTIVES: Prognostic stratification of patients with alcoholic hepatitis (AH)
      may improve the clinical management and facilitate clinical trials. We aimed at
      developing a scoring system capable of providing prognostic stratification of
      patients with AH. METHODS: Patients with biopsy-proven AH were prospectively
      included between 2000 and 2006. The biochemical, clinical, portal hemodynamic and
      histological parameters were evaluated. A Cox regression model was used for
      univariate and multivariate analyses. A predictive score was built using
      variables obtained at admission identified in the multivariate analysis. The
      resulting score was validated in an independent prospective cohort. RESULTS: In
      total, 103 patients with biopsy-proven AH were included in the study cohort. Age,
      serum bilirubin, serum creatinine, and international normalized ratio (INR)
      independently predicted 90-day mortality. We generated the Age, serum Bilirubin,
      INR, and serum Creatinine (ABIC) score: (age x 0.1) + (serum bilirubin x 0.08) +
      (serum creatinine x 0.3) + (INR x 0.8). The area under the curve (AUC) was 0.82.
      Using the Kaplan-Meier analysis with the cutoff values of 6.71 and 9.0, we
      identified patients with low, intermediate, and high risk of death at 90 days
      (100%, 70%, and 25% of survival rate, respectively). Using the same cutoff
      values, the ABIC score also stratified patients according to their risk of death
      at 1 yr. These results were validated by a confirmatory cohort (N = 80).
      CONCLUSIONS: The ABIC score is a new tool that allows the stratification of risk
      of death in patients with AH at 90 days and 1 yr. This score can help improve the
      management of these patients and also help to perform clinical trials.

PMID- 18721243
TI  - Erythrocyte-mediated delivery of dexamethasone in patients with mild-to-moderate
      ulcerative colitis, refractory to mesalamine: a randomized, controlled study.
AB  - BACKGROUND AND AIM: Nearly 25% of patients with ulcerative colitis (UC) requiring
      steroids therapy become steroid-dependent after 1 yr, and virtually all develop
      steroid-related adverse events. We planned a controlled study to investigate the
      efficacy and safety of dexamethasone 21-P (Dex 21-P) encapsulated into
      erythrocytes (DEE). MATERIALS AND METHODS: Forty patients with mild-to-moderate
      UC, refractory to mesalamine, were randomly assigned to one of the following
      three treatments: two DEE infusions 14 days apart (group A, N = 20), oral
      prednisolone (0.5 mg/kg for 14 days followed by a 6 mg/weekly tapering (group B,
      N = 10), and sham infusions (group C, N = 10). The clinical, biochemical, and
      endoscopic parameters were monitored at inclusion and after 8 wk. RESULTS: In
      group A, a mean dose of 9.9 +/- 4.1 mg Dex 21-P was loaded into autologous
      erythrocytes at each infusion. At 8 wk, 15 patients in group A (75%), 8 in group
      B (80%), and 1 in group C (10%, P < 0.001 vs A and B) were in clinical and
      endoscopic remission. When compared with the baseline values, C-reactive protein
      (CRP) dropped in groups A (1.6 mg/dL vs 0.4 mg/dL, P= 0.006) and B (1.0 vs 0.5,
      P= 0.02), but not in group C. No steroid-related adverse events were apparent in
      the patient treated with DEE, compared with 8 out of 10 patients on oral steroids
      (P< or = 0.01). CONCLUSION: Low doses of Dex (mean total dose +/- 20 mg) loaded
      into autologous erythrocytes were significantly more effective than sham
      infusions in terms of symptoms relief, endoscopic, and biochemical improvements
      in UC patients refractory to mesalamine. In addition, in contrast to oral
      prednisolone (mean total dose +/- 1 g), no steroid-related adverse events were
      induced.

PMID- 18721244
TI  - Efficacy and safety of entecavir in patients with chronic hepatitis B and
      advanced hepatic fibrosis or cirrhosis.
AB  - OBJECTIVE: The efficacy and safety of entecavir in patients with chronic
      hepatitis B and advanced liver fibrosis/cirrhosis was assessed from three large,
      randomized, multicenter, phase III studies. PATIENTS AND METHODS: These studies
      enrolled patients (> or = 16 yr) with chronic hepatitis B, elevated alanine
      aminotransferase (ALT) levels, and compensated liver disease. Two trials enrolled
      nucleos(t)ide-naive patients randomized to at least 48 wk of treatment with
      entecavir 0.5 mg/day or lamivudine 100 mg/day. The third trial randomized
      lamivudine-refractory patients to 48 wk of entecavir 1 mg/day or lamivudine 100
      mg/day. In this post hoc descriptive analysis, the efficacy and safety in
      patients with advanced liver fibrosis/cirrhosis (Ishak fibrosis stages 4-6) were
      examined for consistency with those seen in the overall study populations.
      RESULTS: Of the 1,633 treated patients, 245 had advanced liver fibrosis/cirrhosis
      (120 entecavir and 125 lamivudine). Among entecavir-treated patients with
      advanced liver fibrosis, improvement in Ishak fibrosis was observed in 57% of
      nucleos(t)ide-naive hepatitis B e antigen (HBeAg)-positive patients, 59% of
      nucleos(t)ide-naive HBeAg-negative patients, and 43% of lamivudine-refractory
      HBeAg-positive patients versus 49%, 53%, and 33% of lamivudine-treated patients
      with advanced liver fibrosis. The overall trends in other histologic, virologic,
      biochemical, and serologic outcomes in entecavir- versus lamivudine-treated
      patients with advanced liver fibrosis/cirrhosis were consistent with those
      observed in the overall study populations in each trial. The treatment was well
      tolerated. CONCLUSION: These data confirm that the performance of entecavir
      relative to that of lamivudine in patients with advanced liver fibrosis/cirrhosis
      was consistent with the relationship observed in the overall treated population.

PMID- 18721245
TI  - Tryptophan catabolites regulate mucosal sensitization to ovalbumin in respiratory
      airways.
AB  - BACKGROUND: Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in
      tryptophan catabolism, is important in generating tolerance at the foetal
      maternal interface. Studies using 1-methyl-tryptophan (1-MT), the specific
      inhibitor of IDO, showed that this enzyme is important in interferon-gamma (IFN
      gamma)-dependent inhibition of allergic inflammation in the respiratory airway
      during immunotherapy. AIMS OF STUDY: We investigated the role of IDO in the
      development of allergic sensitization, leading to allergic inflammation and
      airway hyper-responsiveness (AHR). METHODS: We used a mouse model to generate
      mucosal tolerance to lipopolysaccharide-free ovalbumin (OVA) following repeated
      intranasal inoculation of OVA over a 3-day period. We tested the successful
      induction of tolerance by subsequent intraperitoneal (i.p.) sensitization
      followed by intranasal challenge with OVA. A slow-release pellet of 1-MT
      implanted into mice was used to block IDO activity prior to repeated intranasal
      inoculation of OVA. We measured T-cell proliferation in response to OVA,
      determined airway inflammation, and measured AHR to intranasal methacholine to
      investigate the role of IDO in sensitization to OVA. RESULTS: Repeated intranasal
      administration of OVA generated tolerance and prevented a subsequent
      sensitization to OVA via the i.p. route. This response was inhibited in mice
      receiving a slow-release pellet of 1-MT. However, we successfully reconstituted
      tolerance in mice receiving 1-MT following intra-peritoneal injection of a
      mixture of kynurenine and hydroxyanthranilic acid. CONCLUSION: Our data suggest
      that, in addition to their role in IFN-gamma-mediated inhibition of allergic
      airway inflammation, products of tryptophan catabolism play an important role in
      the prevention of sensitization to potential allergens in the respiratory airway.

PMID- 18721246
TI  - Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis.
      Meta-analysis of randomized, double-blind, placebo-controlled, clinical trials.
AB  - RATIONALE: Several randomized, double-blind, placebo-controlled clinical trials
      have demonstrated the efficacy of mometasone furoate nasal spray (MFNS) in the
      treatment of allergic rhinitis (AR) thus allowing for a meta-analysis to
      determine the overall treatment effect. METHODS: A comprehensive search of the
      MEDLINE, LILACS, SCOPUS, and the Cochrane Library databases up to 31 October,
      2007 was carried out. Randomized, double-blind, placebo-controlled, clinical
      trials evaluating the efficacy of MFNS in patients with AR compared to placebo
      were included. Total nasal symptom scores (TNSS), individual nasal symptoms,
      total non-nasal symptom scores (TNNSS) and nasal airflow were analysed as the
      standardized mean difference (SMD). Meta-analysis was performed with the random
      or the fixed effect models depending on heterogeneity, by using revman 5
      software. DATA SYNTHESIS: Sixteen of the 113 identified articles met the
      inclusion criteria. For MFNS efficacy on TNSS, 2998 participants were analysed:
      1534 received MFNS and 1464 placebo. Mometasone furoate nasal spray was
      associated with a significant reduction in TNSS (SMD -0.49, 95% CI: -0.60 to 
      0.38; P < 0.00001; I(2) = 50.1%). A significant effect on SMD for nasal
      stuffiness/congestion (-0.41; 95% CI: -0.56 to -0.27), rhinorrhoea (-0.44; 95%
      CI: -0.66 to -0.21), sneezing (-0.40; 95% CI: -0.57 to -0.23) and nasal itching (
      0.39; 95% CI: -0.53 to -0.25) was also demonstrated. Mometasone furoate nasal
      spray treated subjects also showed a significant reduction in TNNSS (-0.30; 95%
      CI: -0.43 to -0.18). The proportion of patients with adverse events was similar
      for MFNS and placebo (0.99; 95% CI: 0.81-1.20; P = 0.91). CONCLUSIONS: This meta
      analysis provides a level Ia evidence for the efficacy of MFSN in the treatment
      of AR vs placebo. Adverse events frequency was similar in both groups.

PMID- 18721247
TI  - Symptoms to pollen and fruits early in life and allergic disease at 4 years of
      age.
AB  - BACKGROUND: The predictive value of reported early symptoms to pollen or fruits
      on later allergic disease is unclear. Our aim is to evaluate if symptoms to
      pollen and/or to fruits early in life are associated with allergic disease and
      sensitization to pollen at 4 years. METHODS: The study included 3619 children
      from the Barn (Children), Allergy, Milieu, Stockholm, Epidemiology project
      (BAMSE) birth cohort. Reported symptoms of wheeze, sneeze or rash to birch, grass
      or weed, symptoms (vomiting, diarrhea, rash, facial edema, sneeze, or wheeze) to
      fruits including tree-nuts at 1 or 2 years of age, and definitions of asthma,
      rhinitis and eczema at 4 years were derived from questionnaire data.
      Sensitization to pollen allergens was defined as allergen-specific IgE-antibodies
      to any pollen (birch/timothy/mugwort) > or =0.35 kU(A)/l. RESULTS: At 1 or 2
      years of age, 6% of the children were reported to have pollen-related symptoms,
      6% had symptoms to fruits, and 1.4% to both pollen and fruits. Children with
      symptoms to both pollen and fruits at 1 or 2 years of age had an increased risk
      for sensitization to any pollen allergen at age 4 (OR(adj) = 4.4, 95% CI = 2.1
      9.2). This group of children also had a substantially elevated risk for
      developing any allergic disease (asthma, rhinitis, or eczema) at 4 years
      irrespective of sensitization to pollen (OR(adj) = 8.6, 95% CI = 4.5-16.4).
      CONCLUSIONS: The prevalence of reported symptoms to pollen and fruits is very low
      in early childhood. However, children with early symptoms to both pollen and
      fruits appear to have a markedly elevated risk for allergic disease.

PMID- 18721249
TI  - Comparison of static automated perimetry and semi-automated kinetic perimetry in
      patients with bilateral visible optic nerve head drusen.
AB  - PURPOSE: Until now there has been no standardized, systemic approach to
      diagnostics in patients with optic nerve head drusen (ONHD). This study compares
      visual field (VF) results obtained with static automated perimetry (SAP) and semi
      automated kinetic perimetry (SKP) in patients with bilateral visible ONHD.
      METHODS: Visual fields in 26 eyes (13 patients) with ONHD were obtained by
      Humphrey Field Analyser II (SAP) and Octopus 101 (SKP) equipment and classified
      by three masked observers. Pairs of VFs were considered equivalent if the
      descriptions given by both methods matched. Individual reaction time (RT) was
      assessed during SKP. Fifteen healthy volunteers were examined as control
      material. RESULTS: Visual field pairs matched in 19 eyes (three normal VFs, 16
      arcuate defects). In the remaining eight eyes SKP provided more information in
      concentric constriction of the VF (two eyes) and SAP provided more information on
      paracentral scotomas (five eyes). Sensitivity was 69% for SKP, 80% for SAP and
      88% for both methods together. Mean RT assessed using SKP amounted to 909 ms in
      eyes with ONHD and 568 ms in normal subjects (p < 0.0003). The median examination
      duration was 13 mins with SKP and 11 mins with SAP (p = 0.05) in eyes with ONHD,
      and 8 mins in control eyes (p < 0.0001). CONCLUSIONS: In clinical practice it is
      necessary to perform both SAP and SKP in patients with ONHD because the VF
      defects are diverse. In SKP, RT is prolonged in eyes with ONHD compared with
      normal eyes and SKP takes longer than SAP in ONHD eyes.

PMID- 18721248
TI  - Meta-analysis of determinants for pet ownership in 12 European birth cohorts on
      asthma and allergies: a GA2LEN initiative.
AB  - BACKGROUND: Studies on pet ownership as a risk or protective factor for asthma
      and allergy show inconsistent results. This may be on account of insufficient
      adjustment of confounding factors. AIM: The objective of this study was to
      describe determinants of cat and dog ownership in European families with and
      without allergies. METHODS: Within the EU-funded network of excellence GA(2)LEN,
      we performed meta-analyses with data from 12 ongoing European birth cohort
      studies on asthma and allergy. Each of the birth cohort studies enrolled between
      485 and 4089 children. Pet ownership, allergic status (asthma, allergic rhinitis,
      eczema) of parents and siblings, parental education, access to ground floor, and
      number of people living at home were assessed by questionnaires. RESULTS: Among
      the 25 056 families from seven European countries cats (14.9%) were more common
      than dogs (12.0%). Allergic family history significantly reduced the odds to own
      a cat (adjusted combined random-effect OR 0.91; 95% CI 0.85-0.99), or dog (0.90;
      0.86-0.94). A higher parental educational level had even more pronounced effects
      on cat (0.84; 0.71-0.98), and dog ownership (0.61; 0.54-0.70). Elder siblings
      reduced the odds to own cats, but not dogs. Convenient ground access
      significantly increased the odds, whereas crowding at home was not associated
      with cat or dog ownership. CONCLUSIONS: The chances to own a cat or dog were
      significantly reduced in allergic families, in parents with a higher educational
      level, and in homes without convenient ground access. In addition to parental
      allergies, social and housing factors should be considered as potential
      confounders in studies on pet exposure and allergic diseases.

PMID- 18721250
TI  - Sequential therapy with intravitreal bevacizumab and photodynamic therapy for
      idiopathic polypoidal choroidal vasculopathy.

PMID- 18721251
TI  - Efficacy and safety of latanoprost versus pilocarpine/timolol maleate fixed
      combination in patients with primary open-angle glaucoma or ocular hypertension.
AB  - PURPOSE: This study aimed to compare the safety and effect on intraocular
      pressure (IOP) of latanoprost given every evening versus pilocarpine/timolol
      maleate fixed combination (PTFC) given twice daily in patients with primary open
      angle glaucoma (POAG) or ocular hypertension (OH). METHODS: Following a 6-week,
      medicine-free period, qualified patients were randomized for Period 1 to either
      placebo administered every morning and latanoprost every evening or to PTFC
      administered twice daily. After 8 weeks of treatment, IOP was measured at 08.00,
      10.00, 16.00 and 18.00 hours. Patients were then switched to the opposite
      treatment and underwent a second diurnal evaluation at the end of Period 2.
      RESULTS: Thirty-two patients completed this study. They demonstrated diurnal
      baseline IOP of 24.1 +/- 2.4 mmHg. Mean diurnal pressure was 16.8 +/- 2.1 mmHg on
      PTFC and 16.9 +/- 2.5 mmHg on latanoprost (p = 0.60). No statistical difference
      between treatments was observed at any individual time-point except at 10.00
      hours, when the PTFC group demonstrated an IOP of 15.9 +/- 2.3 mmHg and
      latanoprost 16.8 +/- 2.7 mmHg (p = 0.02). There were no statistical differences
      between groups in unsolicited systemic or ocular adverse events (p > 0.05).
      However, the PTFC group showed a narrower pupil diameter (2.3 mm) than the
      latanoprost group (3.7 mm). Additionally, a solicited symptom survey demonstrated
      mild blurred vision, stinging and ocular pain with PTFC (p < 0.001). CONCLUSIONS:
      Both PTFC and latanoprost are efficacious in reducing diurnal IOP in POAG or OH.
      However, PTFC may be more effective in the late morning and may have a greater
      incidence of mild ocular side-effects.

PMID- 18721252
TI  - Sublingual immunotherapy: the quest for innovative adjuvants.

PMID- 18721254
TI  - Impact of maternal atopy and probiotic supplementation during pregnancy on infant
      sensitization.

PMID- 18721255
TI  - Spreading and impact of the World Health Organization's Allergic Rhinitis and its
      impact on asthma guidelines in everyday medical practice in France. Ernani
      survey.
AB  - OBJECTIVES: The aim of this study was to determine the spreading level of the WHO
      ARIA (World Health Organization's Allergic Rhinitis and its Impact on Asthma)
      guidelines among the medical community and their influence on medical practices.
      METHODS: A cross-sectional study based on a questionnaire was performed between
      April and July 2005 on randomly chosen general practitioners (GPs) (943) and ear,
      nose and throat (ENT) physicians (277). RESULTS: About 54.4% of the physicians
      claimed to know the WHO-ARIA guidelines and 49.7% said they followed them. These
      results vary significantly, mainly according to medical specialty (ENT vs. GP).
      In comparison to those who did not know the guidelines, their patients benefited
      more frequently (P<0.0001) from allergen search (42.2% vs. 31.7%), a nasal
      endoscopy (38.3% vs. 26.0%), a follow-up consultation (64.9% vs. 52.6%) and
      written information on rhinitis (30.7% vs. 14.1%). Paradoxically, they do not
      search more frequently for asthma and do not provide different first-line
      treatment strategy and duration.

PMID- 18721256
TI  - Comparison of pre- vs. postmeal administration of miglitol for 3 months in type 2
      diabetic patients.
AB  - AIM: alpha-Glucosidase inhibitors (alphaGIs) primarily modify postprandial plasma
      glucose levels and should be taken just before meals. We previously demonstrated
      that a single administration of miglitol within 30 min after the start of a meal
      was equally effective as when administered just before a meal. We here compared
      pre- vs. postmeal administration of miglitol for 3 months in type 2 diabetic
      patients. METHODS: Thirty-one type 2 diabetic outpatients who had never been
      treated with insulin injections or alphaGIs were randomized to two groups:
      patients in group A were asked to take miglitol just before meals, while patients
      in group B were asked to take miglitol after meals. We measured 1,5
      anhydroglucitol (1,5-AG) and HbA(1C) levels in these patients. RESULTS: The
      administration of miglitol after meals for a 3-month period decreased HbA(1C) and
      increased 1,5-AG levels to the same extent as when administered just before
      meals. The incidence of adverse effects seemed to be unrelated to the timing of
      the miglitol administration. CONCLUSIONS: Our results suggest that if patients
      have difficulty remembering to take miglitol just before meal, they should be
      instructed to take the medicine together with other medicine(s) after the meal;
      this instruction may improve the treatment compliance of diabetic patients.

PMID- 18721257
TI  - Chromium supplementation enhances insulin signalling in skeletal muscle of obese
      KK/HlJ diabetic mice.
AB  - AIM: Chromium is an essential nutrient required for glucose and lipid metabolism.
      Laboratory and clinical evidences indicate that chromium supplementation may
      improve insulin sensitivity by enhancing intracellular signalling. Considerable
      evidence suggests that serine phosphorylation of insulin receptor substrate 1
      (IRS1) at 307 residue (IRS1-Ser307) inhibits insulin signalling and results in
      peripheral insulin resistance. Therefore, we investigated whether chromium
      associated insulin action was mediated by modulation of IRS1-Ser307
      phosphorylation. METHODS: Male KK/HlJ mice (genetically obese and insulin
      resistant) were supplemented daily with chromium-containing milk powder or
      placebo for 7 weeks. In analysing functionally characterized insulin resistance,
      the changes of blood biochemicals, inflammatory factors and insulin signalling
      molecules in skeletal muscle were analysed. RESULTS: Using KK mice model, we
      demonstrated that daily supplementation of trivalent chromium-containing milk
      powder reduced serum levels of glucose, insulin and triglycerides, and improved
      glucose and insulin tolerance. Mechanistic study showed that chromium
      supplementation activated postreceptor insulin signalling such as increasing
      IRS1, IRS1 tyrosine phosphorylation, p85alpha regulatory subunit of
      phosphatidylinositol 3-kinase and glucose transporter 4 expression, stimulating
      Akt activity, downregulating c-Jun N-terminal kinase (JNK) activity and
      decreasing IRS1 ubiquitinization and insulin resistance-associated IRS1
      phosphorylation (IRS1-Ser307) in skeletal muscle. In addition, chromium
      supplementation attenuated pro-inflammatory cytokine expression in both blood
      circulation and skeletal muscle. CONCLUSION: Our data suggest that chromium
      containing milk powder supplementation can provide a beneficial effect in
      diabetic subjects by enhancing insulin signalling in skeletal muscle. The
      improvement in insulin signalling by chromium was associated with the decreased
      IRS1-Ser307 phosphorylation, JNK activity and pro-inflammatory cytokine
      production.

PMID- 18721258
TI  - PROCEED: Prospective Obesity Cohort of Economic Evaluation and Determinants:
      baseline health and healthcare utilization of the US sample.
AB  - AIM: To summarize baseline characteristics, health conditions, resource
      utilization and resource cost for the US population for the 90-day period
      preceding enrolment, stratified by body mass index (BMI) and the presence of
      abdominal obesity (AO). METHODS: PROCEED (Prospective Obesity Cohort of Economic
      Evaluation and Determinants) is a multinational, prospective cohort of control
      (BMI 20-24.0 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)) and obese (BMI >or= 30
      kg/m(2)) subjects with AO and without AO [non-abdominal obesity (NAO)], defined
      by waist circumference (WC) >102 and 88 cm for males and females, respectively.
      Subjects were recruited from an Internet consumer panel. Outcomes were self
      reported online. Self-reported anthropometric data were validated. Prevalence of
      conditions and utilization is presented by BMI class and AO within BMI class.
      Differences in prevalence and means were evaluated. RESULTS: A total of 1067
      overweight [n = 474 (NAO: n = 254 and AO: n = 220)] and obese [n = 493 (NAO: n =
      39 and AO: n = 454)] subjects and 100 controls were recruited. Self-reported
      weight (r = 0.92) and WC (r = 0.87) were correlated with measured assessments.
      Prevalence of symptoms was significantly higher in groups with higher BMI, as
      were hypertension (p < 0.0001), diabetes (p < 0.0001) and sleep apnoea (p <
      0.0001). Metabolic risk factors increased with the BMI class. Among the
      overweight class, subjects with AO had significantly more reported respiratory,
      heart, nervous, skin and reproductive system symptoms. Overweight subjects with
      AO reported a significantly higher prevalence of diabetes (13%) compared with
      overweight subjects with NAO (7%, p = 0.04). Mean healthcare cost was
      significantly higher in the higher BMI classes [control ($456 +/- 937) vs.
      overweight ($1084 +/- 3531) and obese ($1186 +/- 2808) (p < 0.0001)]. CONCLUSION:
      An increasing gradient of symptoms, medical conditions, metabolic risk factors
      and healthcare utilization among those with a greater degree of obesity was
      observed. The independent effect of AO on health and healthcare utilization
      deserves further study with a larger sample size.

PMID- 18721259
TI  - LRP-associated protein gene (LRPAP1) and susceptibility to degenerative dementia.
AB  - Difference in genetic makeup of lipid metabolizing proteins may increase
      susceptibility to dementia. The aim of this study was to investigate variations
      in two lipid metabolizing genes, low-density lipoprotein receptor-related protein
      associated protein gene (LRPAP) and apolipoprotein E (APOE), in vascular and
      degenerative dementias. This hospital-based association study included 147
      patients with dementia and 163 age-matched controls. Genotyping for LRPAP1 intron
      5 insertion/deletion and APOEHhaI polymorphism was carried out by polymerase
      chain reaction (PCR)/PCR-restriction fragment length polymorphism method. The
      frequency of DD genotype and *D allele of LRPAP gene was high in degenerative
      dementias compared with controls (76.6% vs. 44.8% and 86.4% vs. 69.3%,
      respectively) suggesting increased susceptibility [P < 0.0001, odds ratio (OR)
      =3.76 for DD genotype and P < 0.0001, OR = 2.80 for D allele]. Vascular dementia
      patients showed statistically insignificant but increasing trend for allele I
      (40.0% vs. 30.7%). We also observed significant association of APOEepsilon4
      allele with degenerative dementias (P < 0.0001, OR =5.35). Our study suggests
      that LRPAP1-D and APOE E4 alleles significantly increase the susceptibility to
      degenerative dementias.

PMID- 18721260
TI  - High-resolution genetic mapping of mammalian motor activity levels in mice.
AB  - The generation of motor activity levels is under tight neural control to execute
      essential behaviors, such as movement toward food or for social interaction. To
      identify novel neurobiological mechanisms underlying motor activity levels, we
      studied a panel of chromosome substitution (CS) strains derived from mice with
      high (C57BL/6J strain) or low motor activity levels (A/J strain) using automated
      home cage behavioral registration. In this study, we genetically mapped the
      expression of baseline motor activity levels (horizontal distance moved) to mouse
      chromosome 1. Further genetic mapping of this trait revealed an 8.3-Mb
      quantitative trait locus (QTL) interval. This locus is distinct from the QTL
      interval for open-field anxiety-related motor behavior on this chromosome. By
      data mining, an existing phenotypic and genotypic data set of 2445 genetically
      heterogeneous mice (http://gscan.well.ox.ac.uk/), we confirmed linkage to the
      peak marker at 79 970 253 bp and refined the QTL to a 312-kb interval containing
      a single gene (A830043J08Rik). Sequence analysis showed a nucleotide deletion in
      the 3' untranslated region of the Riken gene. Genome-wide microarray gene
      expression profiling in brains of discordant F(2) individuals from CS strain 1
      showed a significant upregulation of Epha4 in low-active F(2) individuals.
      Inclusion of a genetic marker for Epha4 confirmed that this gene is located
      outside of the QTL interval. Both Epha4 and A830043J08Rik are expressed in brain
      motor circuits, and similar to Epha4 mutants, we found linkage between reduced
      motor neurons number and A/J chromosome 1. Our findings provide a novel QTL and a
      potential downstream target underlying motor circuitry development and the
      expression of physical activity levels.

PMID- 18721261
TI  - Subtle gene-environment interactions driving paranoia in daily life.
AB  - It has been suggested that genes impact on the degree to which minor daily
      stressors cause variation in the intensity of subtle paranoid experiences. The
      objective of the present study was to test the hypothesis that catechol-O
      methyltransferase (COMT) Val(158)Met and brain-derived neurotrophic factor (BDNF)
      Val(66)Met in part mediate genetic effects on paranoid reactivity to minor
      stressors. In a general population sample of 579 young adult female twins, on the
      one hand, appraisals of (1) event-related stress and (2) social stress and, on
      the other hand, feelings of paranoia in the flow of daily life were assessed
      using momentary assessment technology for five consecutive days. Multilevel
      regression analyses were used to examine moderation of daily life stress-induced
      paranoia by COMT Val(158)Met and BDNF Val(66)Met genotypes. Catechol-O
      methyltransferase Val carriers displayed more feelings of paranoia in response to
      event stress compared with Met carriers. Brain-derived neurotrophic factor Met
      carriers showed more social-stress-induced paranoia than individuals with the
      Val/Val genotype. Thus, paranoia in the flow of daily life may be the result of
      gene-environment interactions that can be traced to different types of stress
      being moderated by different types of genetic variation.

PMID- 18721262
TI  - Two divergent genes encoding L-myo-inositol 1-phosphate synthase1 (CaMIPS1) and 2
      (CaMIPS2) are differentially expressed in chickpea.
AB  - L-myo-inositol 1-phosphate synthase (MIPS; EC5.5.1.4) catalyses the rate-limiting
      step in inositol biosynthetic pathway, and is extremely widespread in living
      organisms including plants. Several plants possess multiple copies of MIPS
      gene(s) indicating a possibility of differential expression of each gene to
      perform distinct physiological functions. To explore this, two MIPS genes
      (CaMIPS1 and CaMIPS2) were isolated from a drought-tolerant plant chickpea. Both
      genes are extremely divergent in respect to their introns, at the same time
      retaining 85% identity to their exons and functionally complementing inositol
      auxotroph Schizosaccharomyces pombe. Expression analysis showed both genes were
      expressed in all organs except seed, where only CaMIPS2 transcript was detected.
      Under environmental stresses, only CaMIPS2 was induced whereas CaMIPS1 expression
      remained same, which could be explained by the divergence of their 5' upstream
      regulatory sequences. Remarkably, both gene products exhibited similar
      biochemical characteristics; however, CaMIPS2 retained higher activity than
      CaMIPS1 at a high temperature and salt concentration. Furthermore, functional
      expression of CaMIPS2 in S. pombe results better growth response than CaMIPS1
      under stress environment. Taken together, our results suggest that CaMIPS1 and
      CaMIPS2 are differentially expressed in chickpea to play discrete though
      overlapping roles in plant; however CaMIPS2 is likely to be evolved through gene
      duplication to function under environmental stresses.

PMID- 18721263
TI  - Cell cycle phase-specific death response of tobacco BY-2 cell line to cadmium
      treatment.
AB  - The character of programmed cell death (PCD) in plants differs in connection with
      the context, triggering factors and differentiation state of the target cells. To
      study the interconnections between cell cycle progression and cell death
      induction, we treated synchronized tobacco BY-2 cells with cadmium ions that
      represent a general abiotic stressor influencing both dividing and differentiated
      cells in planta. Cadmium induced massive cell death after application in all
      stages of the cell cycle; however, both the progression and the forms of the cell
      death differed pronouncedly. Apoptosis-like PCD induced by cadmium application in
      the S and G2 was characterized by pronounced internucleosomal DNA fragmentation.
      In contrast, application of cadmium in M and G1 phases was not accompanied by DNA
      cleavage, indicating suppression of autolysis and non-programmed character of the
      death. We interpret these results in the context of the situation in planta,
      where the induction of apoptosis-like PCD in the S and G2 phase might be
      connected with a need to preserve genetic integrity of dividing meristematic
      cells, whereas suppression of PCD response in differentiated cells (situated in
      G1/G0 phase) might help to avoid death of the whole plant, and thus enable
      initiation of the recovery and adaptation processes.

PMID- 18721264
TI  - The chloroplast avoidance response decreases internal conductance to CO2
      diffusion in Arabidopsis thaliana leaves.
AB  - The relationship between chloroplast arrangement and diffusion of CO(2) from
      substomatal cavities to the chloroplast stroma was investigated in Arabidopsis
      thaliana. Chloroplast position was manipulated by varying the amount of blue
      light and by cytochalasin D (CytD) treatment. We also investigated two
      chloroplast positioning mutants. Chloroplast arrangement was assessed by the
      surface area of chloroplasts adjacent to intercellular airspaces (S(c)). Although
      it has been previously shown that long-term acclimation to high light is linked
      with a large S(c), we found that the short-term chloroplast avoidance response
      reduces S(c). This effect was not apparent in the blue-light-insensitive phot2
      mutant, which did not show the avoidance response. As expected, the smaller S(c)
      induced by the avoidance response was coupled to a similar decrease in internal
      conductance. This reduction in internal conductance resulted in an increased
      limitation of the rate of photosynthesis. The limiting effect of S(c) on internal
      conductance and photosynthesis was also shown in chup1, a mutant with a constant
      small S(c) as the result of an unusual chloroplast arrangement. We conclude that
      chloroplast movements in A. thaliana can rapidly alter leaf morphological
      parameters, and this has significant consequences for the diffusion of CO(2)
      through the mesophyll.

PMID- 18721265
TI  - Arabidopsis transcript and metabolite profiles: ecotype-specific responses to
      open-air elevated [CO2].
AB  - A Free-Air CO(2) Enrichment (FACE) experiment compared the physiological
      parameters, transcript and metabolite profiles of Arabidopsis thaliana Columbia-0
      (Col-0) and Cape Verde Island (Cvi-0) at ambient (approximately 0.375 mg g(-1))
      and elevated (approximately 0.550 mg g(-1)) CO(2) ([CO(2)]). Photoassimilate pool
      sizes were enhanced in high [CO(2)] in an ecotype-specific manner. Short-term
      growth at elevated [CO(2)] stimulated carbon gain irrespective of down-regulation
      of plastid functions and altered expression of genes involved in nitrogen
      metabolism resembling patterns observed under N-deficiency. The study confirmed
      well-known characteristics, but the use of a time course, ecotypic genetic
      differences, metabolite analysis and the focus on clusters of functional
      categories provided new aspects about responses to elevated [CO(2)]. Longer-term
      Cvi-0 responded by down-regulating functions favouring carbon accumulation, and
      both ecotypes showed altered expression of genes for defence, redox control,
      transport, signalling, transcription and chromatin remodelling. Overall, carbon
      fixation with a smaller commitment of resources in elevated [CO(2)] appeared
      beneficial, with the extra C only partially utilized possibly due to disturbance
      of the C : N ratio. To different degrees, both ecotypes perceived elevated
      [CO(2)] as a metabolic perturbation that necessitated increased functions
      consuming or storing photoassimilate, with Cvi-0 emerging as more capable of
      acclimating. Elevated [CO(2)] in Arabidopsis favoured adjustments in reactive
      oxygen species (ROS) homeostasis and signalling that defined genotypic markers.

PMID- 18721266
TI  - Stress-induced expression of an activated form of AtbZIP17 provides protection
      from salt stress in Arabidopsis.
AB  - Membrane-associated basic-leucine zipper (bZIP) transcription factors that reside
      in the endoplasmic reticulum represent a newly described class of plant stress
      sensor/transducers. The bZIP factors are anchored in endoplasmic reticulum (ER)
      membranes with their C-terminal tails facing the ER lumen and their N terminii,
      which contain transcriptional components, facing the cytosol. In response to
      stress, cytosolic components of the transcription factors are released by
      proteolysis and move to the nucleus where they promote the up-regulation of
      stress response genes. One such stress sensor/transducer in Arabidopsis is
      AtbZIP17, which is activated in response to salt stress. With the aim of
      enhancing salt tolerance, a constitutively activated form of AtbZIP17, truncated
      before its membrane-anchor domain, was introduced into transgenic plants. When
      placed under the control of a constitutive promoter, the activated form of
      AtbZIP17 up-regulated stress response genes under unstressed conditions, but
      caused a substantial delay in plant development. When the activated form of
      AtbZIP17 was placed under the control of stress-inducible promoter, development
      was normal under unstressed conditions. Under salt stress conditions, the stress
      inducible expression of the activated AtbZIP17 enhanced salt tolerance as
      demonstrated by chlorophyll bleaching and seedling survival assays.

PMID- 18721267
TI  - Nitric oxide production occurs after cytosolic alkalinization during stomatal
      closure induced by abscisic acid.
AB  - Abscisic acid (ABA) raised the cytosolic pH and nitric oxide (NO) levels in guard
      cells while inducing stomatal closure in epidermis of Pisum sativum. Butyrate (a
      weak acid) reduced the cytosolic pH/NO production and prevented stomatal closure
      by ABA. Methylamine (a weak base) enhanced the cytosolic alkalinization and
      aggravated stomatal closure by ABA. The rise in guard cell pH because of ABA
      became noticeable after 6 min and peaked at 12 min, while NO production started
      at 9 min and peaked at 18 min. These results suggested that NO production was
      downstream of the rise in cytosolic pH. The ABA-induced increase in NO of guard
      cells and stomatal closure was prevented by 2-phenyl-4,4,5,5-tetramethyl
      imidazoline-1-oxyl 3-oxide (cPTIO, a NO scavenger) and partially by N-nitro-L-Arg
      methyl ester (L-NAME, an inhibitor of NO synthase). In contrast, cPTIO or L-NAME
      had only a marginal effect on the pH rise induced by ABA. Ethylene glycol
      tetraacetic acid (EGTA, a calcium chelator) prevented ABA-induced stomatal
      closure while restricting cytosolic pH rise and NO production. We suggest that
      during ABA-induced stomatal closure, a rise in cytosolic pH is necessary for NO
      production. Calcium may act upstream of cytosolic alkalinization and NO
      production, besides its known function as a downstream component.

PMID- 18721268
TI  - Responses of Brassica oleracea cultivars to infestation by the aphid Brevicoryne
      brassicae: an ecological and molecular approach.
AB  - Intraspecific variation in resistance or susceptibility to herbivorous insects
      has been widely studied through bioassays. However, few studies have combined
      this with a full transcriptomic analysis. Here, we take such an approach to study
      the interaction between the aphid Brevicoryne brassicae and four white cabbage
      (Brassica oleracea var. capitata) cultivars. Both under glasshouse and field
      conditions, two of the cultivars clearly supported a faster aphid population
      development than the other two, indicating that aphid population development was
      largely independent of the environmental conditions. Genome-wide transcriptomic
      analysis using 70-mer oligonucleotide microarrays based on the Arabidopsis
      thaliana genome showed that only a small number of genes were differentially
      regulated, and that this regulation was highly cultivar specific. The temporal
      pattern in the expression behaviour of two B. brassicae-responsive genes in all
      four cultivars together with targeted studies employing A. thaliana knockout
      mutants revealed a possible role for a trypsin-and-protease inhibitor in defence
      against B. brassicae. Conversely, a xyloglucan endotransglucosylase seemed to
      have no effect on aphid performance. Overall, this study shows clear
      intraspecific variation in B. brassicae susceptibility among B. oleracea
      cultivars under glasshouse and field conditions that can be partly explained by
      certain differences in induced transcriptional changes.

PMID- 18721269
TI  - Existence of an immunoglobulin G component of naturally occurring HLA class I
      antibodies that are not directed against self-antigens in human serum.
AB  - We compared the frequency of immunoglobulin G (IgG) type of human leukocyte
      antigen (HLA) class I antibodies between patients with systemic lupus
      erythematosus (SLE) and healthy controls using a highly sensitive FlowPRA method.
      Sixteen of 130 normal healthy males and 2 of 10 normal females without a history
      of pregnancy (none had ever been transfused) possessed HLA class I antibodies. In
      SLE, male, but not female patients, showed a significant increase in the
      frequency of the antibodies compared with the corresponding controls. The
      antibodies did not appear to be involved in the development of SLE because of no
      substantial relationship to the incidence of cytopenia or SLE disease activity
      index score. Each individual had 1-31 types of HLA class I antibodies.
      Interestingly, HLA class I antibodies did not correspond to the individual's own
      HLA antigens. Eight of 32 types of HLA class I antigens detected were rare in the
      Japanese population. These results suggest that an IgG component of naturally
      occurring HLA class I antibodies exists in human serum and that these antibodies
      are not antibodies against self-antigens.

PMID- 18721270
TI  - Loss of heterozygosity at 6p21 underlying [corrected] HLA class I downregulation
      in Chinese primary esophageal squamous cell carcinomas.
AB  - Loss or downregulation of human leukocyte antigen (HLA) class I molecules is a
      widespread mechanism used by tumor cells to avoid tumor recognition by cytotoxic
      T lymphocytes favoring tumor immune escape. Multiple molecular mechanisms are
      responsible for these altered HLA class I tumor phenotypes, such as the loss of
      heterozygosity (LOH) at chromosome region 6p21.3. In this study, we used
      immunohistological techniques with a highly selective panel of anti-HLA
      monoclonal antibodies to analyze the expression of HLA class I molecules in 84
      formalin-fixed, paraffin-embedded section and 49 frozen-fresh tissues of primary
      esophageal squamous cell carcinomas (pESCC) from Chinese patients. To elucidate
      the underlying mechanism of HLA class I loss or downregulation, we also analyzed
      LOH of previously selected microsatellite markers located in chromosomes 6 and 15
      by polymerase chain reaction. DNA was obtained from frozen-fresh tumor tissues
      and surrounding stroma to define the LOH associated with chromosomes 6p21 and
      15q21. Our results showed that HLA-A, HLA-B/C, HLA class I heavy chain, beta2
      microglobuline, and HLA class I complex were lost or downregulated in pESCC
      (P<0.0001), and were moderately associated with the microsatellite alterations in
      HLA class I gene regions, correlated with patients' age, tumor's location, and
      stage, and indicated that LOH at 6p21.3 is a frequent mechanism that leads to HLA
      class I abnormalities in pESCC.

PMID- 18721271
TI  - HLA-A, -B and -DRB1 allele frequencies in the Bangladeshi population.
AB  - Population genetic studies have become an invaluable tool because of the extreme
      polymorphism found at some of the loci of the human leukocyte antigen (HLA)
      system. In this study, we are reporting for the first time the genetic
      polymorphism of 141 healthy unrelated Bangladeshi Bangalees living in central
      region of Dhaka. We studied the HLA-A, -B and -DRB1 loci using polymerase chain
      reaction with sequence-specific primers. The allelic frequencies, two and three
      locus haplotype frequencies were statistically analyzed. A total of 16 HLA-A
      alleles, 26 HLA-B alleles and 14 HLA-DRB1 alleles were detected. A*33-B*44
      (8.15%) was the most common two loci class 1 haplotype, whereas A*33-B*44-DRB1*07
      (6.38%) was the most frequent three loci haplotype. The most common HLA-A, HLA-B
      and HLA-DRB1 alleles were A*33 (17.02%), B*15 (19.5%) and DRB1*15 (29.07%),
      respectively. Construction of phylogenetic tree using average linkage between
      groups and correspondence analysis showed close associations with Indian non
      tribal random Dravidians, north Indian Hindus and some relations with Mongolian
      and Pakistani populations. We believe this data will provide useful information
      for bone marrow registry, legal medicine, disease association and anthropological
      studies.

PMID- 18721272
TI  - Genetic affinities of north and northeastern populations of India: inference from
      HLA-based study.
AB  - India is like a microcosm of the world in terms of its diversity; religion,
      climate and ethnicity which leads to genetic variations in the populations. As a
      highly polymorphic marker, the human leukocyte antigen (HLA) system plays an
      important role in the genetic differentiation studies. To assess the genetic
      diversity of HLA class II loci, we studied a total of 1336 individuals from north
      India using DNA-based techniques. The study included four endogamous castes
      (Kayastha, Mathurs, Rastogies and Vaishyas), two inbreeding Muslim populations
      (Shias and Sunnis) from north India and three northeast Indian populations
      (Lachung, Mech and Rajbanshi). A total of 36 alleles were observed at DRB1 locus
      in both Hindu castes and Muslims from north, while 21 alleles were seen in
      northeast Indians. At the DQA1 locus, the number of alleles ranged from 11 to 17
      in the studied populations. The total number of alleles at DQB1 was 19, 12 and 20
      in the studied castes, Muslims and northeastern populations, respectively. The
      most frequent haplotypes observed in all the studied populations were DRB1*0701
      DQA1*0201-DQB1*0201 and DRB1*1501-DQA1*0103-DQB1*0601. Upon comparing our results
      with other world populations, we observed the presence of Caucasoid element in
      north Indian population. However, differential admixturing among Sunnis and Shias
      with the other north Indians was evident. Northeastern populations showed genetic
      affinity with Mongoloids from southeast Asia. When genetic distances were
      calculated, we found the north Indians and northeastern populations to be
      markedly unrelated.

PMID- 18721273
TI  - Evaluation of the class II region of the major histocompatibility complex of the
      greyhound with the genomic matching technique and sequence-based typing.
AB  - The class II region of the major histocompatibility complex was evaluated in 25
      greyhounds by sequence-based typing and the genomic matching technique (GMT). Two
      new DLA-DRB1 alleles were identified. Twenty-four dogs carried the DLA
      DRB1*01201/DQA1*00401/DQB1*01303/DQB1*01701 haplotype, which carries two DQB1
      alleles. One haplotype was identified from which DQB1 and DQA1 appeared to be
      deleted. The GMT enabled detection of DQB1 copy number, discrimination of the
      different class II haplotypes and the identification of new, possibly
      biologically relevant polymorphisms.

PMID- 18721274
TI  - Expression and regulation of non-classical HLA-G in renal cell carcinoma.
AB  - Under physiological conditions, the non-classical major histocompatibility
      complex class Ib molecule human leukocyte antigen G (HLA-G) is selectively
      expressed in placental trophoblasts, thymus and cornea. In pathological
      situations, HLA-G expression was frequently found in tumour cells of distinct
      origin, thereby allowing these tumour cells to escape immune surveillance.
      Although HLA-G expression occurs at a relatively high frequency in renal cell
      carcinoma (RCC) of the clear cell subtype, the molecular mechanisms of its
      aberrant expression in RCC has not yet been determined. Therefore, the
      constitutive and cytokine-mediated HLA-G expression as well as its mode of
      regulation was investigated. In addition to HLA-G-specific mRNA expression,
      membrane-bound and soluble/shed HLA-G protein was determined. Eight of 14 RCC
      cell lines analysed (57%) exhibited HLA-G-specific transcripts, whereas only 6 of
      14 RCC cell lines (43%) expressed HLA-G protein, suggesting a post
      transcriptional control of HLA-G in some cases. Treatment of RCC cell lines with
      either interferon-gamma or interleukin-10, respectively, increased HLA-G-specific
      mRNA and protein in six of eight HLA-G(+) RCC lines (75%), but not in HLA-G(-)
      RCC cells. A 5'-aza-2-deoxycytidine (5-Aza-dC)-mediated demethylation of the HLA
      G promoter DNA resulted in an enhanced HLA-G expression in four of six RCC cell
      lines, whereas a de novo induction of HLA-G was only observed in one HLA-G(-) RCC
      cell line on treatment with 5-Aza-dC. Thus, there exist multiple mechanisms
      controlling HLA-G expression in RCC, which might also have an impact on the
      development of RCC-specific immunotherapies.

PMID- 18721275
TI  - HLA-G polymorphism and transitional cell carcinoma of the bladder in a Brazilian
      population.
AB  - The morphologic appearance and clinical behavior of the human urinary bladder
      papillary transitional cell carcinoma (TCC) probably result from a complex
      interaction between carcinogenic insults and host resistance during the patient's
      life. While the main recognized risk factors are of environmental origin (e.g.
      smoking), relatively little information exists about the susceptibility to TCC
      development. The human leukocyte antigen G (HLA-G) molecule plays an important
      role in immune response regulation and has been implicated in the inhibition of
      the cytolytic function of natural killer and cytotoxic T cells. Several lines of
      evidence indicate that HLA-G polymorphisms influence the expression level and
      production of different HLA-G isoforms. The aim of this study was to explore a
      possible influence of the HLA-G polymorphism on the susceptibility to urinary
      bladder TCC development and progression in smokers and nonsmokers Brazilian
      subjects. The HLA-G locus was found to be associated with susceptibility to TCC
      development and progression. The G*0104 allelic group (specially the G*010404
      allele) and the G*0103 allele were associated with a tobacco-dependent influence
      on TCC development. The G*0104 group was associated with progression to high
      grade tumors, irrespective of smoking habit, while the G*0103 allele was
      associated to high-grade tumor only in smoking patients. Our results are an
      evidence that the HLA-G locus itself, or as part of an extended haplotype
      encompassing this chromosome region (particularly the HLA-A given the high
      linkage disequilibrium observed between them in this data series), may be
      associated with TCC susceptibility and tumor progression, suggesting a tobacco
      dependent influence of these polymorphisms.

PMID- 18721276
TI  - The T244I variant of the interleukin-7 receptor-alpha gene and multiple
      sclerosis.
AB  - Several but not all studies have provided evidence for the association between
      multiple sclerosis (MS) and the T244I variant of the interleukin-7 receptor-alpha
      gene (IL7RA), rs6897932. We performed a new replication case-control study in 599
      MS patients and 594 healthy controls, all Caucasians from the south of Spain. The
      genotype and allele frequencies differed between MS cases and controls. The IL7RA
      rs6897932 C allele and the CC genotype were found to be factors for disease
      susceptibility [per allele odds ratio (OR) 1.32, 95% CI 1.1-1.6, P=0.0031; per CC
      genotype vs TT + TC genotypes, OR 1.5, 95% CI 1.18-1.87, P=0.0007]. The combined
      data analysis included 3324 cases and 5032 controls of Europeans and Americans of
      European origin resulting in stronger association with similar OR (P=1.9 x 10E
      9). These findings in our sample support previous reported association studies
      between IL7RA rs6897932 and MS.

PMID- 18721277
TI  - Positive association of HLA-DRB1*15 with Dupuytren's disease in Caucasians.
AB  - Dupuytren's disease (DD) is a permanent nodular condition affecting the palms and
      digits of the hands, leading to progressive shortening and contractures of the
      digits often resulting in diminished function and severe deformity. DD is thought
      to be one of the most common hereditary connective tissue disorders in
      Caucasians. To elucidate further the aetiology of DD, we compared the HLA-DRB1
      phenotype frequencies of DD patients (n=67) against the HLA-DRB1 phenotype
      frequencies observed in a control population (n=537). HLA-DRB1*15 phenotype
      frequency was higher in DD positive Caucasoids (37.3%) when compared with control
      data (20.9%) (corrected P=0.029): we conclude that in Caucasoids of European
      origin, HLA-DRB1*15 is associated with risk of developing DD.

PMID- 18721278
TI  - Association of allograft inflammatory factor-1 gene polymorphism with rheumatoid
      arthritis.
AB  - Human allograft inflammatory factor-1 (AIF-1) is a cytoplasmic protein primarily
      identified in human and rat allografts, and data from several studies suggest an
      important role for AIF-1 in inflammatory processes. The aim of this study was to
      examine the association between AIF1 rs2269475:C>T polymorphism and rheumatoid
      arthritis (RA). AIF1 genotype was determined by means of the polymerase chain
      reaction-restriction fragment length polymorphism method in 276 White patients
      with RA and 236 healthy subjects. The frequency of the AIF1 rs2269475 TT genotype
      was significantly higher in the patients with RA than in the controls (OR=5.59,
      95% CI: 1.22-25.55). The frequency of T allele carriers in the patient group with
      RA was 31.9% vs 19.1% among controls (P=0.0003). Moreover, the frequency of
      individuals positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies
      was significantly elevated in the T allele carriers (OR=8.82, 95% CI: 2.06-37.7).
      It is noteworthy that no significant linkage disequilibria between the AIF1 C/T
      and DRB1 alleles associated with RA development and anti-CCP antibody production
      [including the most frequent, i.e. *04 (32.7%) and *01 (23.5%)] (P>0.1) were
      found. Our results show that the AIF1 rs2269475 T allele is associated with
      increased risk of RA development. Moreover, the frequency of individuals positive
      for anti-CCP antibodies is significantly increased among T allele carriers.

PMID- 18721279
TI  - A new HLA-A*02 null allele, HLA-A*9213N.
AB  - A novel HLA-A*02 null allele, differing from HLA-A*02010101 at codon 60 (TGG
      tryptophan-->TAG stop), is described.

PMID- 18721280
TI  - A new HLA-B*40 allele, HLA-B*4085, identified by sequence-based typing in the
      Korean population.
AB  - A new HLA-B*4085 showed one nucleotide difference from B*400201 at the position
      500 of exon 3, resulting in a coding change from Thr to Ile (T143I).

PMID- 18721281
TI  - A novel HLA-B*40 allele, B*4086, was identified by sequence-based typing in a
      Chinese donor.
AB  - We report the identification of a novel HLA-B*40 allele, B*4086, which was
      detected during our routine sequence-specific oligonucleotide (SSO) HLA typing of
      a sample from a bone marrow donor and confirmed with sequence-based typing. The
      name HLA-B*4086 was officially assigned by the WHO Nomenclature Committee in
      February 2008.

PMID- 18721284
TI  - Abstracts of the World Ophthalmology Congress. June 28-July 2, 2008. Hong Kong.

PMID- 18721282
TI  - Characterization and sequence analysis of the novel HLA-Cw*040105 allele in a
      Chinese Uygur individual.
AB  - A novel human leukocyte antigen (HLA) allele, HLA-Cw*040105, was identified in a
      Chinese Uygur individual. It differs from the closest allele Cw*04010101 by four
      nucleotides at position nt 60 (C>T) in exon 1, genomic nt 477 (A>T) in intron 2,
      nt 835(T>C), and nt 850 (C>T) in exon 3.

PMID- 18721306
TI  - Senescence processes and their regulation.

PMID- 18721307
TI  - The control of chlorophyll catabolism and the status of yellowing as a biomarker
      of leaf senescence.
AB  - The pathway of chlorophyll catabolism during leaf senescence is known in a fair
      amount of biochemical and cell biological detail. In the last few years, genes
      encoding a number of the catabolic enzymes have been characterized, including the
      key ring-opening activities, phaeophorbide a oxygenase (PaO) and red chlorophyll
      catabolite reductase (RCCR). Recently, a gene that modulates disassembly of
      chlorophyll-protein complexes and activation of pigment ring-opening has been
      isolated by comparative mapping in monocot species, positional cloning exploiting
      rice genomics resources and functional testing in Arabidopsis. The corresponding
      gene in pea has been identified as Mendel's I locus (green/yellow cotyledons).
      Mutations in this and other chlorophyll catabolic genes have significant
      consequences, both for the course of leaf senescence and senescence-like stress
      responses, notably hypersensitivity to pathogen challenge. Loss of chlorophyll
      can occur via routes other than the PaO/RCCR pathway, resulting in changes that
      superficially resemble senescence. Such 'pseudosenescence' responses tend to be
      pathological rather than physiological and may differ from senescence in
      fundamental aspects of biochemistry and regulation.

PMID- 18721308
TI  - Senescence-associated degradation of chloroplast proteins inside and outside the
      organelle.
AB  - Leaf proteins, and in particular the photosynthetic proteins of plastids, are
      extensively degraded during senescence. Although this involves massive amounts of
      protein, the mechanisms responsible for chloroplast protein degradation are
      largely unknown. Degradation within the plastid itself is supported by the
      observation that chloroplasts contain active proteases, and that chloroplasts
      isolated from senescing leaves can cleave Rubisco to release partially digested
      fragments. It is less clear whether chloroplasts can complete Rubisco
      degradation. Chloroplastic proteases are likely involved in the breakdown of the
      D1 and LHCII proteins of photosystem II. Small senescence-associated vacuoles
      (SAVs) with high-proteolytic activity develop in senescing leaf cells, and there
      is evidence that SAVs contain chloroplast proteins. Thus, an extra-plastidic
      pathway involving SAVs might participate in the degradation of some chloroplast
      proteins. Plastidic and extra-plastidic pathways might cooperate in the
      degradation of chloroplast proteins, or they might represent alternative,
      redundant pathways for photosynthetic protein degradation.

PMID- 18721309
TI  - Leaf nitrogen remobilisation for plant development and grain filling.
AB  - A major challenge of modern agriculture is to reduce the excessive input of
      fertilisers and, at the same time, to improve grain quality without affecting
      yield. One way to achieve this goal is to improve plant nitrogen economy through
      manipulating nitrogen recycling, and especially nitrogen remobilisation, from
      senescing plant organs. In this review, the contribution of nitrogen
      remobilisation efficiency (NRE) to global nitrogen use efficiency (NUE), and
      tools dedicated to the determination of NRE are described. An overall examination
      of the physiological, metabolic and genetic aspects of nitrogen remobilisation is
      presented.

PMID- 18721310
TI  - Leaf senescence and nutrient remobilisation in barley and wheat.
AB  - Extensive studies have been undertaken on senescence processes in barley and
      wheat and their importance for the nitrogen use efficiency of these crop plants.
      During the senescence processes, proteins are degraded and nutrients are re
      mobilised from senescing leaves to other organs, especially the developing grain.
      Most of the proteins degraded reside in the chloroplasts, with Rubisco
      constituting the most dominant protein fraction. Despite intensive studies, the
      proteases responsible for Rubisco degradation have not yet been identified.
      Evidence for degradation of stromal proteins outside of chloroplasts is
      summarised. Rubisco is thought to be released from chloroplasts into vesicles
      containing stroma material (RCB = Rubisco-containing bodies). These vesicles may
      then take different routes for their degradation. Transcriptome analyses on
      barley and wheat senescence have identified genes involved in degradative,
      metabolic and regulatory processes that could be used in future strategies aimed
      at modifying the senescence process. The breeding of crops for characters related
      to senescence processes, e.g. higher yields and better nutrient use efficiency,
      is complex. Such breeding has to cope with the dilemma that delayed senescence,
      which could lead to higher yields, is correlated with a decrease in nutrient use
      efficiency. Pinpointing regulatory genes involved in senescence might lead to
      tools that could effectively overcome this dilemma.

PMID- 18721311
TI  - Metabolic regulation of leaf senescence: interactions of sugar signalling with
      biotic and abiotic stress responses.
AB  - Sugars are important signals in the regulation of plant metabolism and
      development. During stress and in senescing leaves, sugars often accumulate. In
      addition, both sugar accumulation and stress can induce leaf senescence.
      Infection by bacterial and fungal pathogens and attack by herbivores and gall
      forming insects may influence leaf senescence via modulation of the sugar status,
      either by directly affecting primary carbon metabolism or by regulating steady
      state levels of plant hormones. Many types of biotic interactions involve the
      induction of extracellular invertase as the key enzyme of an apoplasmic phloem
      unloading pathway, resulting in a source-sink transition and an increased
      hexose/sucrose ratio. Induction of the levels of the phytohormones ethylene and
      jasmonate in biotic interactions results in accelerated senescence, whereas an
      increase in plant- or pathogen-derived cytokinins delays senescence and results
      in the formation of green islands within senescing leaves. Interactions between
      sugar and hormone signalling also play a role in response to abiotic stress. For
      example, interactions between sugar and abscisic acid (ABA) signalling may be
      responsible for the induction of senescence during drought stress. Cold
      treatment, on the other hand, can result in delayed senescence, despite sugar and
      ABA accumulation. Moreover, natural variation can be found in senescence
      regulation by sugars and in response to stress: in response to drought stress,
      both drought escape and dehydration avoidance strategies have been described in
      different Arabidopsis accessions. The regulation of senescence by sugars may be
      key to these different strategies in response to stress.

PMID- 18721312
TI  - Transcription factors regulating leaf senescence in Arabidopsis thaliana.
AB  - Senescence is a highly regulated process, eventually leading to cell and tissue
      disintegration: a physiological process associated with nutrient (e.g. nitrogen)
      redistribution from leaves to reproductive organs. Senescence is not observed in
      young leaves, indicating that repressors efficiently act to suppress cell
      degradation during early leaf development and/or that senescence activators are
      switched on when a leaf ages. Thus, massive regulatory network re-wiring likely
      constitutes an important component of the pre-senescence process. Transcription
      factors (TFs) have been shown to be central elements of such regulatory networks.
      Here, we used quantitative real-time polymerase chain reaction (qRT-PCR) analysis
      to study the expression of 1880 TF genes during pre-senescence and early
      senescence stages of leaf development, using Arabidopsis thaliana as a model. We
      show that the expression of 185 TF genes changes when leaves develop from half to
      fully expanded leaves and finally enter partial senescence. Our analysis
      identified 41 TF genes that were gradually up-regulated as leaves progressed
      through these developmental stages. We also identified 144 TF genes that were
      down-regulated during senescence. A considerable number of the senescence
      regulated TF genes were found to respond to abiotic stress, and salt stress
      appeared to be the major factor controlling their expression. Our data indicate a
      peculiar fine-tuning of developmental shifts during late-leaf development that is
      controlled by TFs.

PMID- 18721313
TI  - Supply of nitrogen can reverse senescence processes and affect expression of
      genes coding for plastidic glutamine synthetase and lysine-ketoglutarate
      reductase/saccharopine dehydrogenase.
AB  - Nitrogen availability has a strong influence on developmental processes in
      plants. We show that the time of nitrogen supply regulates the course of leaf
      senescence in flag leaves of Hordeum vulgare. The senescence-specific decrease in
      chlorophyll content and photosystem II efficiency is clearly delayed when plants
      are fertilised with nitrate at the onset of leaf senescence. Concurrently, the
      additional supply of nitrate affects expression patterns of two marker genes of
      nitrogen metabolism. As shown by quantitative RT-PCR analyses, senescence
      specific downregulation of plastidic glutamine synthetase (GS2) and senescence
      specific upregulation of lysine-ketoglutarate reductase/saccharopine
      dehydrogenase (LKR/SDH) are both clearly retarded. Depletion of nitrogen in
      experiments using hydroponic growth systems results in premature primary leaf
      senescence. The already started senescence processes can be even reversed by
      later nitrogen addition, as proved by a further increase in photosystem II
      efficiency and chlorophyll content, returning to the high values of controls
      which had not been deprived of nitrogen. Although both addition of nitrate or
      ammonium effectively reversed nitrogen depletion-induced primary leaf senescence,
      addition of urea did not. Additionally, effects of nitrogen supply on the course
      of leaf senescence were analysed in the model plant Arabidopsis thaliana. Leaves
      of A. thaliana show the same reversion of senescence processes after receiving
      additional nitrogen supply, indicating that the nitrogen response of leaf
      development is conserved in different plant species.

PMID- 18721314
TI  - Early leaf senescence is associated with an altered cellular redox balance in
      Arabidopsis cpr5/old1 mutants.
AB  - Reactive oxygen species (ROS) are the inevitable by-products of essential
      cellular metabolic and physiological activities. Plants have developed
      sophisticated gene networks of ROS generation and scavenging systems. However,
      ROS regulation is still poorly understood. Here, we report that mutations in the
      Arabidopsis CPR5/OLD1 gene may cause early senescence through deregulation of the
      cellular redox balance. Genetic analysis showed that blocking stress-related
      hormonal signalling pathways, such as ethylene, salicylic acid, jasmonic acid,
      abscisic acid and sugar, did not affect premature cell death and leaf senescence.
      We took a bioinformatics approach and analysed publicly available transcriptome
      data of presymptomatic cpr5/old1 mutants. The results demonstrate that many genes
      in the ROS gene network show at least fivefold increases in transcripts in
      comparison with those of wild-type plants, suggesting that presymptomatic
      cpr5/old1 mutants are in a state of high-cellular oxidative stress. This was
      further confirmed by a comparative, relative quantitative proteomics study of
      Arabidopsis wild-type and cpr5/old1 mutant plants, which demonstrated that
      several Phi family members of glutathione s-transferases significantly increased
      in abundance. In summary, our genetic, transcriptomic and relative quantitative
      proteomics analyses indicate that CPR5 plays a central role in regulating redox
      balance in Arabidopsis.

PMID- 18721315
TI  - Transcriptional regulation of plant senescence: from functional genomics to
      systems biology.
AB  - Leaf senescence is an active process that involves the increased expression of
      many hundreds of genes. Many putative transcription factors show enhanced
      transcription during leaf senescence in Arabidopsis and functional analysis of
      these should help to indicate their role in controlling gene expression during
      leaf senescence. In this paper, we describe the analysis of knockout insertion
      mutants in two different senescence-enhanced genes, one encodes a heat shock
      transcription factor and the other a zinc finger protein. Plants mutated in these
      genes show accelerated leaf senescence and reduced tolerance to drought stress,
      indicating that expression of these genes during senescence has a protective role
      to maintain viability during this essential developmental process. Analysis of
      gene expression changes in both mutants compared to the wild-type plants
      indicates an increased rate of senescence but does not show clearly the pathway
      that is dependent on these genes for expression. The complexities of signalling
      networks in plant stress and the plasticity of plant responses mean that the
      direct consequences of mutation are very difficult to define. The usefulness of
      this type of approach to address the burning question of how senescence is
      regulated is discussed, and an alternative approach aimed at a more global
      analysis of gene regulation using systems biology methods is described.

PMID- 18721316
TI  - A novel upstream regulator of WRKY53 transcription during leaf senescence in
      Arabidopsis thaliana.
AB  - Arabidopsis WRKY proteins comprise a family of zinc finger-type transcription
      factors involved in the regulation of gene expression during pathogen defence,
      wounding, trichome development and senescence. To better understand the
      regulatory role of the senescence-related WRKY53 factor, we identified upstream
      regulatory factors using the yeast one-hybrid system. Among others, we identified
      a DNA-binding protein with a so far unknown function that contains a
      transcriptional activation domain and a kinase domain with similarities to HPT
      kinases. In vitro studies revealed that this activation domain protein (AD
      protein) can phosphorylate itself and that phosphorylation increases its DNA
      binding activity to the WRKY53 promoter region. Using the yeast two-hybrid
      system, an interaction with proteins that were previously shown to bind to the
      WRKY53 promoter was tested. The AD protein interacted with MEKK1. The interaction
      with MEKK1 was confirmed in vivo by bimolecular fluorescence complementation
      (BiFC); however, the AD protein was not phosphorylated by MEKK1 in vitro and vice
      versa. This indicates that there may be competition between WRKY53 and AD protein
      for binding of MEKK1 at the WRKY53 promoter. Overexpression and knockout of the
      respective gene resulted in changes in transcription levels of WRKY53, indicating
      that AD protein is a positive regulator of WRKY53 expression. Expression of the
      AD protein gene can be induced by hydrogen peroxide treatment and reduced by
      jasmonic acid treatment, as previously shown for WRKY53.

PMID- 18721317
TI  - Identification and characterization of novel senescence-associated genes from
      barley (Hordeum vulgare) primary leaves.
AB  - Leaf senescence is the final developmental stage of a leaf. The progression of
      barley primary leaf senescence was followed by measuring the senescence-specific
      decrease in chlorophyll content and photosystem II efficiency. In order to
      isolate novel factors involved in leaf senescence, a differential display
      approach with mRNA populations from young and senescing primary barley leaves was
      applied. In this approach, 90 senescence up-regulated cDNAs were identified. Nine
      of these clones were, after sequence analyses, further characterized. The
      senescence-associated expression was confirmed by Northern analyses or
      quantitative RealTime-PCR. In addition, involvement of the phytohormones ethylene
      and abscisic acid in regulation of these nine novel senescence-induced cDNA
      fragments was investigated. Two cDNA clones showed homologies to genes with a
      putative regulatory function. Two clones possessed high homologies to barley
      retroelements, and five clones may be involved in degradation or transport
      processes. One of these genes was further analysed. It encodes an ADP
      ribosylation factor 1-like protein (HvARF1) and includes sequence motifs
      representing a myristoylation site and four typical and well conserved ARF-like
      protein domains. The localization of the protein was investigated by confocal
      laser scanning microscopy of onion epidermal cells after particle bombardment
      with chimeric HvARF1-GFP constructs. Possible physiological roles of these nine
      novel SAGs during barley leaf senescence are discussed.

PMID- 18721318
TI  - Natural developmental variations in leaf and plant senescence in Arabidopsis
      thaliana.
AB  - Leaf senescence is a developmentally regulated process that contributes to
      nutrient redistribution during reproductive growth and finally leads to tissue
      death. Manipulating leaf senescence through breeding or genetic engineering may
      help to improve important agronomic traits, such as crop yield and the storage
      life of harvested organs. Here, we studied natural variations in the regulation
      of plant senescence among 16 Arabidopsis thaliana accessions. Chlorophyll content
      and the proportion of yellow leaves were used as indicator parameters to
      determine leaf and plant senescence respectively. Our study indicated significant
      genotype effects on the onset and development of senescence. We selected three
      late- and five early-senescence accessions for further physiological studies. The
      relationship between leaf and plant senescence was accession-dependent. There was
      a significant correlation between plant senescence and the total number of
      leaves, siliques and plant bolting age. We monitored expression of two senescence
      marker genes, SAG12 and WRKY53, to evaluate progression of senescence. Our data
      revealed that chlorophyll content does not fully reflect leaf age, because even
      fully green leaves had already commenced senescence at the molecular level.
      Integrating senescence parameters, such as the proportion of senescent leaves, at
      the whole plant level provided a better indication of the molecular status of the
      plant than single leaf senescence parameters.

PMID- 18721319
TI  - Meristem aging is not responsible for age-related changes in growth and abscisic
      acid levels in the Mediterranean shrub, Cistus clusii.
AB  - To obtain new insights into the mechanisms underlying aging in perennials, we
      measured abscisic acid levels, growth and other stress indicators in leaves of
      Cistus clusii Dunal plants of different ages grown under Mediterranean field
      conditions. Recently emerged leaves from 9-year-old plants were compared to those
      of 1-year-old plants (obtained from cuttings from 9-year-old plants) to evaluate
      the effects of meristem aging on plant aging. Rooting and successful
      establishment of the cuttings allowed us to compare the physiology of plants with
      old meristems, but of different size. Plants obtained from cuttings were
      rejuvenated, with new leaves displaying a higher leaf area and chlorophyll
      content, but smaller leaf mass per unit area ratios and endogenous abscisic acid
      levels than those of 9-year-old plants. A comparative study in 1-, 4- and 9-year
      old plants revealed that abscisic acid levels increase during the early stages of
      plant life (with increases of 90% between 1- and 4-year-old plants), but then
      remain constant at advanced developmental stages (between 4- and 9-year-old
      plants). Although leaf biomass was 53% smaller in 9-year-old compared to 4-year
      old plants, the dry matter produced per shoot apical meristem was equivalent in
      both plant groups due to an increased number of leaves per shoot in the former.
      It is concluded that (i) C. clusii plants maintain the capacity to rejuvenate for
      several years; (ii) newly emerged leaves accumulate higher amounts of abscisic
      acid during early stages of plant life, but the levels of this phytohormone later
      remain constant; and (iii) although plant aging leads to the production of
      smaller leaves, the amount of biomass produced per shoot apical meristem remains
      constant at advanced developmental stages.

PMID- 18721320
TI  - Allergy as an organ and a systemic disease.
AB  - Allergic disorders are viewed generally as organ diseases and thus referred to
      organ specialists, such as the ear, nose and throat specialist for rhinitis, the
      pulmonologist for asthma, the dermatologist for dermatitis, and so on. Indeed,
      the systemic nature of allergy is made evident by the fact that the same
      individual may develop during the life different manifestations to a given
      allergen. This is true for example in sensitisation to house dust mites, which
      may start in childhood as atopic dermatitis and later express as asthma or
      rhinitis. The major player in driving the immune response is the T lymphocyte,
      and the T helper subpopulations--Th1 and Th2--as well as the T regulatory cells,
      are involved in orienting tolerance or reactivity to allergens. Interesting
      observations on the systemic or organ-specific actions of T cells were obtained
      by transplantations from allergic donors to non-allergic recipients. Bone marrow
      is able to transfer all allergic manifestations, while lung transplantation
      transfers only asthma. A number of factors are involved in the expression of
      allergy as a systemic or organ disease and deserve deeper investigations. They
      include the antigen presenting cells, the homing of T cells, the cytokine and
      chemokine pattern, and the adhesion molecules.

PMID- 18721321
TI  - Allergy and the gastrointestinal system.
AB  - The gastrointestinal system plays a central role in immune system homeostasis. It
      is the main route of contact with the external environment and is overloaded
      every day with external stimuli, sometimes dangerous as pathogens (bacteria,
      protozoa, fungi, viruses) or toxic substances, in other cases very useful as food
      or commensal flora. The crucial position of the gastrointestinal system is
      testified by the huge amount of immune cells that reside within it. Indeed, gut
      associated lymphoid tissue (GALT) is the prominent part of mucosal-associated
      lymphoid tissue (MALT) and represents almost 70% of the entire immune system;
      moreover, about 80% of plasma cells [mainly immunoglobulin A (IgA)-bearing cells]
      reside in GALT. GALT interacts strictly with gastrointestinal functions in a
      dynamic manner; for instance, by increasing intestinal permeability in replay to
      particular stimulations, or orientating the immune response towards luminal
      content, allowing either tolerance or elimination/degradation of luminal
      antigens, or sometimes provoking damage to the intestinal mucosa, such as in
      coeliac disease or food allergy. The immune mechanisms implicated in these
      actions are very complex and belong to both innate and adaptive immunity; innate
      immunity supplies an immediate non-specific response that is indispensable before
      specific adaptive immunity, which needs 7-10 days to be efficacious, takes place.
      The results of their interactions depend upon different contexts in which contact
      with external agents occurs and may change according to different genetic
      settings of the hosts.

PMID- 18721322
TI  - Allergy and the cardiovascular system.
AB  - The most dangerous and life-threatening manifestation of allergic diseases is
      anaphylaxis, a condition in which the cardiovascular system is responsible for
      the majority of clinical symptoms and for potentially fatal outcome. The heart is
      both a source and a target of chemical mediators released during allergic
      reactions. Mast cells are abundant in the human heart, where they are located
      predominantly around the adventitia of large coronary arteries and in close
      contact with the small intramural vessels. Cardiac mast cells can be activated by
      a variety of stimuli including allergens, complement factors, general anesthetics
      and muscle relaxants. Mediators released from immunologically activated human
      heart mast cells strongly influence ventricular function, cardiac rhythm and
      coronary artery tone. Histamine, cysteinyl leukotrienes and platelet-activating
      factor (PAF) exert negative inotropic effects and induce myocardial depression
      that contribute significantly to the pathogenesis of anaphylactic shock.
      Moreover, cardiac mast cells release chymase and renin that activates the
      angiotensin system locally, which further induces arteriolar vasoconstriction.
      The number and density of cardiac mast cells is increased in patients with
      ischaemic heart disease and dilated cardiomyopathies. This observation may help
      explain why these conditions are major risk factors for fatal anaphylaxis. A
      better understanding of the mechanisms involved in cardiac mast cell activation
      may lead to an improvement in prevention and treatment of systemic anaphylaxis.

PMID- 18721324
TI  - Allergy and the eye.
AB  - The eye represents an ideal and frequent site for the allergic reactions. The
      term 'allergic conjunctivitis' refers to a collection of disorders that affect
      the lid, conjunctiva and/or cornea. Even though the diagnosis is essentially
      clinical, local tests such as cytology, conjunctival provocation and tear
      mediator analysis can be performed. The immunoglobulin E (IgE)-mediated mechanism
      does not explain completely the severity and the clinical course of chronic
      allergic ocular diseases such as vernal (VKC) and atopic keratoconjunctivitis
      (AKC), which are probably also related to T cell-mediated responses, massive
      eosinophil attraction and activation and non-specific hypersensitivity. An
      altered balance between T helper type 1 (Th1) and Th2 cells and between Th1- and
      Th2-types of cytokines is thought to be responsible of the development of ocular
      allergic disorders. New findings suggest that a wide range of cytokines,
      chemokines, proteases and growth factors are involved by complex interwoven
      interactions rather than distinct and parallel pathways. In addition, several non
      specific enzymatic systems may be activated during acute and chronic allergic
      inflammation, thus contributing to the complex pathogenesis of the disease.
      Current drug treatment for ocular allergy targets the key mechanisms involved in
      the development of clinical disease: mast cells with mast cell stabilizers,
      histamine with histamine receptor antagonists and inflammation with
      corticosteroids, severe inflammation with immunomodulators. None of these agents
      lacks side effects and none abolishes signs and symptoms completely. New
      therapeutic strategies are still needed to respond to the complex pathogenesis of
      severe forms of ocular allergy such as VKC and AKC.

PMID- 18721323
TI  - Allergy and the lung.
AB  - Among the 'allergic' conditions involving the lung, asthma is the more frequent
      and the most extensively investigated, although asthma itself may be caused by
      different disorders. The triggering event in allergic subjects is the reaction
      allergen-specific immunoglobulin E (IgE) that activates mast cells and initiates
      a complex and redundant inflammatory process, where cells, cytokines and adhesion
      molecules are involved at different stages. In fact, mucosal eosinophilic
      inflammation is one of the distinctive features of asthma and the particular T
      helper type 2 (Th2) phenotype of allergic patients favours it. In general, the
      clinical severity of asthma correlates well with the degree of inflammation. None
      the less, other phenomena such as non-specific bronchial hyperresponsiveness and
      remodelling intervene in the pathophysiology of allergic asthma. These phenomena
      are only partially inflammation-related. In particular, the remodelling of the
      bronchial wall seems to start very early in life and also seems to be a
      distinctive histological feature of the asthmatic bronchus. The recent
      introduction of biological treatments (monoclonal antibodies) has allowed
      elucidation of some of the pathogenic features of allergic asthma.

PMID- 18721325
TI  - Allergy and the nose.
AB  - Allergic rhinitis (AR) is the most common immunological disorder and is
      characterized by an immunoglobulin E (IgE)-mediated inflammation induced by the
      allergen exposure. This review will consider some issues concerning
      pathophysiological aspects of AR: impact on asthma, response to decongestion,
      link with infections, response to specific immunotherapy, relationship with
      adiposity, effects on quality of life (QoL) and allergic inflammation. AR, even
      though not a serious illness, may be a clinically relevant disorder as it may
      present numerous complications and affect QoL, as reported in this review.
      Therefore, the management of AR patients should be rigorously careful and multi
      disciplinary.

PMID- 18721326
TI  - Allergy and the skin.
AB  - Allergic skin disorders include urticaria, angioedema, contact dermatitis and
      atopic dermatitis, but the model fitting most closely the systemic concept of
      allergy is atopic dermatitis (AD), the pathogenesis of which is linked to a
      complex interaction between skin barrier dysfunction and environmental factors
      such as allergens and microbes. In particular, an important advance was the
      demonstration that the mutation of the skin barrier protein filaggrin is related
      strictly to allergen sensitization and to the development of asthma in subjects
      with AD. The altered skin barrier function, caused by several factors, results in
      the passage of allergens through the skin and to systemic responses. A pivotal
      role in such a response is exerted by Langerhans cells which, via their
      immunoglobulin E (IgE) receptor, capture the allergens and present them to T
      cells. When T helper type 2 (Th2) cells are activated, the production of a
      proinflammatory cytokines and chemokines pattern sustains the persistence of
      inflammation. Known AD-related cytokines are interleukin (IL)-5, IL-13 and tumour
      necrosis factor (TNF)-alpha, with emerging importance for IL-17, which seems to
      drive airway inflammation following cutaneous exposure to antigens, and IL-31,
      which is expressed primarily in skin-homing Th2 cells. Skin-homing is another
      crucial event in AD, mediated by the cutaneous lymphocyte-associated antigens
      (CLA) receptor, which characterizes T cell subpopulations with different roles in
      AD and asthma.

PMID- 18721327
TI  - Breakpoints for posaconazole susceptibility testing: background and discussion
      about the need of establishing values.
AB  - Posaconazole is a new antifungal agent, which exhibits a broad spectrum of
      activity against fungi including Aspergillus terreus, some zygomycetes and
      dematiaceous fungi. Out of the group of triazole antifungal agents, it is the
      only compound for which interpretive breakpoints have not been established have
      not yet been established for Candida spp. As reliable breakpoints are useful in
      the practical management of patients with fungal infections, it is desirable to
      establish the same for all available substances. However, the underlying data of
      the existing breakpoints for other antifungal agents are of varying quality
      because of limited clinical data available. Furthermore, these breakpoints are
      not equally suitable for all testing methods available and they may not be
      suitable for all species to be tested. From the practical point of view, it is
      therefore important not only to establish breakpoints for the reference method
      but also for the inexpensive and easy to perform testing methods, which are
      suitable for smaller laboratories.

PMID- 18721328
TI  - Posaconazole for paediatric patients: status of development and future
      perspectives.
AB  - Posaconazole is a novel oral antifungal triazole with potent and broad-spectrum
      antifungal activity, favourable pharmacokinetic properties and a limited spectrum
      of adverse events. The compound has documented clinical efficacy in the settings
      of oropharyngeal candidiasis, refractory aspergillosis, fusariosis, zygomycosis,
      and as antifungal prophylaxis in high-risk patients with acute myeloblastic
      leukaemia or graft-vs.-host disease. Whereas, posaconazole is approved for use in
      adults, however, the appropriate dosage and the safety of the compound have not
      been systematically investigated in paediatric age groups. This paper reviews the
      relevant pharmacological characteristics of posaconazole, the published data on
      its use in paediatric patients without therapeutic alternative and perspectives
      for the clinical development in paediatric patients at risk for invasive fungal
      infections.

PMID- 18721329
TI  - To treat or not to treat--critically ill patients with candiduria.
AB  - The prevalence of candiduria has increased in patients admitted to intensive care
      units (ICUs) and it has emerged as a common nosocomial infection among critically
      ill patients. Generally, urinary candidiasis should be regarded as a risk factor
      for invasive candidiasis, but not as a disease that needs to be treated on its
      own. However, decision-making in critically ill patients with candiduria may
      become a balancing act, because candiduria may be the only indication for
      invasive candidaemia with significant morbidity and mortality. Of further
      concern, there is a worldwide increase in the incidence of non-albicans spp.
      isolated from urine with highly variable susceptibility to fluconazole, which has
      been the first-line therapy for Candida infections during the last decades. This
      article discusses everyday problems with urinary candidiasis in interdisciplinary
      ICUs.

PMID- 18721330
TI  - Invasive candidiasis in the ICU: evidence based and on the edge of evidence.
AB  - Invasive candidiasis is a common nosocomial infection among critically ill
      patients, constitutes an important cause of sepsis, and is associated with
      significant morbidity and mortality. The Infectious Diseases Society of America
      (IDSA) has created evidence-based guidelines for the management of invasive
      candidiasis. However, several new antifungal agents with excellent activity
      against Candida spp. and favourable safety profiles have been introduced
      successfully in the clinical setting since the IDSA guidelines were published in
      late 2003. Further, the role of antifungals is not entirely clear in the
      intensive care unit (ICU) setting. Therefore, this article discusses daily
      problems in the prophylaxis and treatment of invasive candidasis in
      interdisciplinary ICUs.

PMID- 18721331
TI  - Antifungal treatment strategies in high risk patients.
AB  - We discuss different strategies for the treatment of invasive fungal infections
      (IFI) in high risk patients with a focus on patients experiencing profound and
      prolonged neutropenia, comprising those with acute myelogenous leukaemia (AML) or
      myelodysplastic syndrome (MDS) during remission induction chemotherapy and on
      patients undergoing allogeneic haematopoietic stem cell transplantation (SCT).
      Among these patients, invasive aspergillosis (IA) is the most frequently observed
      form of IFI, as opposed to high risk intensive care unit (ICU) patients in whom
      an increased incidence of invasive candidiasis (IC) can be observed. In both
      groups, initiation of early treatment has a profound impact on mortality rates,
      but adequate diagnostic tools are lacking. These circumstances have led to the
      parallel use of different treatment strategies, e.g. prophylaxis, empiric, pre
      emptive and targeted treatment of IFI. The optimum treatment strategies for these
      severe infections are a matter of extensive research and discussion. A review of
      major clinical trials on the issue reveals that comparisons between different
      treatment strategies cannot be made. Considering the complexity of the issue, we
      advocate an eclectic treatment approach that reduces morbidity and mortality from
      IFI without compromising tolerability. In allogeneic HSCT recipients, patients
      receiving induction chemotherapy for AML or MDS and those under immunosuppressive
      medication for graft vs. host disease after allogeneic HSCT, we recommend
      prophylaxis with posaconazole. For empiric treatment of persistently febrile
      neutropenic patients, we opt for caspofungin as first and liposomal amphotericin
      B deoxycholate (L-AmB) as second line choice. If the diagnosis of IA can be
      established, voriconazole should be favoured over the alternative, liposomal
      amphotericin B (L-AmB). While high risk ICU patients benefit from fluconazole
      prophylaxis for IC, the choice of an optimal agent for targeted therapy depends
      largely on the neutrophil count. In non-neutropenic patients, we recommend an
      echinocandin as the first line treatment option. Patients with susceptible
      Candida spp. may be switched to fluconazole. Caspofungin or micafungin might be
      preferred to anidulafungin in the neutropenic patient. L-AmB is a valuable second
      line treatment option for both groups of patients.

PMID- 18721332
TI  - Posaconazole in intensive care patients I: invasive fungal infections in surgical
      intensive care and case presentation.
AB  - Critically ill patients after extended surgical procedures are at high risk for
      postoperative infections. Fungal infections play a substantial role for
      immunocompromised patients, e.g. after solid organ transplantation or under
      chronic corticoid therapy. Posaconazole, a new broad-spectrum triazole effective
      against Aspergillus and Candida species as well as many fungi that are resistant
      to other antifungals, is well tolerated and can be used as an alternative in
      salvage therapy. Posaconazole can be administered via gavage so that antifungal
      therapy can be switched from an expensive intravenously applied antifungal to
      oral posaconazole at an early stage. Two case reports are presented, which show
      that posaconazole was efficacious and well tolerated following antifungal therapy
      with another azole. It was administered without difficulty via gavage to a
      patient receiving artificial respiration and dialysis.

PMID- 18721333
TI  - Candida infection in HIV positive patients 1985-2007.
AB  - Infection with Candida species remains a major problem in HIV infected patients.
      The analysis of over 15,000 hospitalisations (1985-2007) in the AVK cohort shows
      an increasing incidence of non-albicans species in candida esophagitis. Although
      our analysis shows a decreasing incidence of opportunistic infections like PCP,
      cerebral toxoplasmosis and others since the introduction of highly active
      antiretroviral therapy the incidence of candida esophagitis remains as high as in
      the years before the HAART era. This observation might reflect the development of
      resistance against fluconazole and the selection of non-albicans species as a
      consequence of a long-term prophylactic treatment of HIV+ patients over years.

PMID- 18721334
TI  - A pioneer in research.

PMID- 18721335
TI  - Miomir Cvek (1927-2008).

PMID- 18721336
TI  - Survival of 534 incisors after intra-alveolar root fracture in patients aged 7-17
      years.
AB  - The purpose of the study was to evaluate and assess the survival rate of 534 root
      fractured teeth, including factors that may affect the survival rate but were not
      included in previous long-term studies. Location of fracture was registered as in
      the cervical, cervical/middle, middle and apical one-third of the root, and root
      development was categorized into five stages. Altogether, 383 (78%) showed
      healing of the fracture, with either formation of hard tissue or interposition of
      soft tissue between the fragments. In these teeth, no significant difference was
      found between positions in the root or types of healing. In 325 teeth, the
      healing remained unchanged throughout the control period, while 58 teeth showed a
      posthealing complication. A new injury occurred in 47 teeth; in 21 of these, the
      injury healed spontaneously, in four after endodontic treatment. Increased
      mobility of the coronal fragment was recorded for 32 teeth, and in 11 of these,
      the looseness of the fragment was so pronounced that the teeth had to be
      extracted. No healing, i.e. radiolucency in the alveolar bone, adjacent to
      fracture, took place in 109 teeth (22%). Of these teeth, 34 were extracted during
      the observation time while 75 (69%) showed healing after endodontic therapy. At
      the final assessment of survival (including all parameters) of 534 root fractured
      teeth, 425 (80%) showed survival and 109 (20%) were extracted during the
      observation period. It was concluded that the survival of root-fractured teeth
      was high for up to 10 years of observation (mean = 63 months). The highest
      frequency of tooth loss (70%) was found in 77 teeth with horizontal fractures
      restricted to the cervical part of the root. When these teeth were excluded, the
      frequency of survival in remaining teeth rose to 88%.

PMID- 18721337
TI  - Transplantation of primary canines after loss or ankylosis of upper permanent
      incisors. A prospective case series study on healing and survival.
AB  - Primary canines were transplanted to replace lost or ankylosed permanent upper
      incisors. Healing, healing complications and loss and survival were evaluated in
      a prospective case series study. In total, 27 primary canines were transplanted.
      Extraorally posts made of titanium were inserted into the root canal from a
      retrograde direction as an immediate endodontic treatment and as an elongation of
      the short autologous roots. In some cases antiresorptive-regenerative therapy was
      used. Inclusion criteria for the evaluation were a minimal observation period of
      12 months or the observation of complications. The median observation period of
      the analyzed 17 transplants was 26.6 months (min: 6.7 months, max: 54.6 months).
      Sixteen out of seventeen transplants exhibited functional healing until the end
      of the observation or the occurrence of an external influence (another trauma,
      resorption by neighbored tooth). In no case ankylosis or arrest of alveolar
      growth was recorded. In some transplants resorptions not related to infection or
      ankylosis were observed. One transplant exhibited an early infection-related
      complication and was removed. One transplant was resorbed by the developing
      permanent canine and lost. Following another trauma five transplants were lost.
      External influence and new trauma were significantly related to the loss of
      transplants (Fisher's exact test; P = 0.0006 and 0.0034). The estimated survival
      according to a Kaplan-Meier analysis was 40.7 months for all transplants. It was
      significantly shorter for teeth which were lost in relation to an external
      influence (survival 28.4 months vs 44.7 months; log rank test: P = 0.0093). The
      transplantation of primary canines maintains bone and soft tissues of the
      alveolar process. The healing rate is high. However, there is a high incidence of
      repeated trauma episodes, causing a high loss rate. The observation period is
      still limited.

PMID- 18721338
TI  - Characterization of root surface periodontal ligament following avulsion, severe
      intrusion or extraction: preliminary observations.
AB  - This study employed novel topographic and histological techniques to assess
      remaining periodontal ligament (PDL) in a convenience sample of avulsed and
      intruded human permanent incisors and extracted premolars. Seventeen human teeth
      (eight avulsed, five severely intruded and four uninjured extracted) were
      evaluated for the distribution and physical characteristics of adherent root
      surface PDL. The topographic distribution of PDL was assessed by staining roots
      with malachite green and determining the proportion of remaining PDL within
      selected regions on four aspects of each tooth. In order to characterize
      mechanical damage to PDL, serial transverse sections of roots were stained with
      hematoxylin and eosin and examined at magnifications of 40x to 800x. The sections
      were photographed and imaging software was used to calculate the percentage of
      remaining PDL in the circumference of each root section. Topographic analysis
      demonstrated that 54% of the PDL remained on roots of avulsed and severely
      intruded incisors and 36% of the PDL remained on the extracted single-rooted
      premolars. Examination of serial transverse root sections revealed that 58% of
      the PDL remained on roots of avulsed or severely intruded incisors and 54% on
      extracted premolars. Avulsed and severely intruded incisors demonstrated similar
      amounts of retained PDL. In both injuries, almost half of the root surface was
      denuded of PDL.

PMID- 18721339
TI  - Orofacial damage resulting from road accidents.
AB  - The objective of this paper was to study the epidemiological characteristics of
      orofacial damage resulting from road accidents among victims assessed in the
      Oporto delegation of the Legal Medicine Institute, in Portugal. It was also our
      goal to analyze in which way orofacial sequelae was reflected in the victims'
      complete social reintegration.

PMID- 18721341
TI  - Practicability of a tooth rescue concept--the use of a tooth rescue box.
AB  - Healing following replantation of avulsed teeth is dependent upon short
      unphysiologic periods during the extraalveolar phase. A commercially available
      tooth rescue box was developed and distributed at schools in Hessen, a state in
      Germany. Aim of the study was to evaluate the availability times of rescue boxes
      and the storage periods of rescued teeth within the boxes. Two thousand one
      hundred tooth rescue boxes together with a questionnaire were distributed
      predominantly at schools. In case of usage of a box, the questionnaire should be
      filled out by patients and dentists and sent back for evaluation. One hundred
      seventy-two (8.2%) questionnaires were sent back. Eighteen questionnaires were
      incomplete. In the remaining 154 tooth rescue boxes, a total of 201 avulsed teeth
      and tooth crown fragments were rescued. When accidents occurred near a stored
      rescue box, the availability time was short (median: 5 min). It was significantly
      longer (median: 35 min) when the location of the accident was distant to a stored
      box. Storage of avulsed teeth in the tooth rescue box was longer (median: 2 h)
      than storage of fractured crown fragments (median: 1 h). Lay people (teachers,
      pupils) used the rescue boxes correctly without professional help or even advice
      through telephone. The usage of the tooth rescue box seemed to be self
      explanatory and plausible to lay persons, very short availability times resulted
      when accidents occurred near stored boxes. Thus, an excellent healing prognosis
      can be anticipated after replantation. The storage periods of avulsed teeth
      before the commencement of treatment exceed by far the periods that are
      acceptable for alternative but unphysiologic media (saline, saliva, milk). It is
      concluded that tooth rescue boxes should be distributed at locations prone to
      tooth traumas (schools, kindergartens, sporting facilities, public pools) to
      enhance the prognosis of avulsed teeth. Emergency units (hospitals, ambulances)
      should be equipped with tooth rescue boxes as well as every dentist. Tooth rescue
      boxes are recommended for families with children.

PMID- 18721340
TI  - Outcomes of dental fracture injury as related to laser Doppler flow measurements
      of pulpal blood-flow level.
AB  - Laser Doppler flowmetry (LDF) is a non-invasive method to assess pulpal blood
      flow (PBF). Dental fracture injuries have been associated with significant PBF
      reduction The purpose of this study was: (i) to evaluate whether the severity of
      outcomes of dental fracture injuries may be related to LDF measurements of PBF,
      and (ii) to investigate whether outcomes of dental fracture injuries may predict
      PBF levels. The relationship between outcomes and PBF measurements was analyzed
      in 72 permanent maxillary incisors of 52 consecutive dental trauma patients. The
      diagnostic outcome group comprised 72 incisors with a type I (absence of
      sensitivity, periapical radiolucency, and grey discoloration of crown) (n = 42),
      type II (loss of sensitivity) (n = 16), or type III (loss of sensitivity,
      periapical radiolucency, and/or grey discoloration of crown) diagnosis. At each
      session, when an injured permanent maxillary incisor was recorded, a
      contralateral homologous tooth was used as a control. An ordinal stepwise
      regression was completed to assess the degree of association between PBF
      measurements and diagnostic outcomes. A logistic regression analysis was used to
      compute the odds ratios for the outcome features for incisor non-injury controls
      vs two outcome groups: type II (n = 16) and type III (n = 14). PBF measurements
      that were significantly associated with more severe outcome were PBF levels of
      <or=6 perfusion units (PU) (106.70 odds ratio) (P = 0.000). Significant increase
      in the risk of a PBF level of <or=6 PU occurred with a type III outcome (32.49
      odds ratio) (P = 0.004). PBF measurements were related to the severity of adverse
      outcomes. Diagnoses of treatment outcomes predicted the presence of specific PBF
      levels.

PMID- 18721342
TI  - Basketball players' experience of dental injury and awareness about mouthguard in
      China.
AB  - The objective of the present study was to describe the occurrence of orofacial,
      particularly dental injuries in basketball, and to survey the athletes' awareness
      concerning the use of mouthguards during basketball training and competition. A
      pilot questionnaire was designed and tested with basketball players. Two hundred
      and thirty-six male athletes were surveyed. Seventy-seven players were
      professional players. Exactly 80.6% professionals and 37.7% semi-professional
      athletes had an experience of oral soft tissue laceration and dental injuries in
      basketball practice. The difference between the two groups is significant. The
      incidence of dental and oral injuries was related to the length of training time.
      About 59% of the athletes ranked the risk of orofacial and dental injury in
      basketball as medium. Although the awareness of mouthguards among the basketball
      players was very high (80.1%), only one of them had used the custom-made
      mouthguard. Most of the athletes gained the knowledge about mouthguards from
      foreign players (33.5%), media (24.8%) and teammates/classmates (24.3%). The
      influence of dentists was very weak. Athletes should be informed about the high
      risk of oral injuries when participating in contact sports. Dentists should play
      a more significant role in the program of promoting mouthguard use to prevent the
      occurrence of oral injury in sport participation.

PMID- 18721343
TI  - Vascular endothelial growth factor (VEGF) response to dental trauma: a
      preliminary study in rats.
AB  - BACKGROUND: Successful periodontal healing and pulpal revascularization after
      trauma may be age-related. After dental trauma, age-related impaired angiogenesis
      may play a role in the revascularization rate during the healing process.
      OBJECTIVES: The aim of the present preliminary in vivo study was to detect the
      presence of vascular endothelial growth factor (VEGF) in venous and whole blood
      from the alveolar socket immediately post-tooth extraction. MATERIALS AND
      METHODS: The study consisted of 16 Wistar rats divided into two groups: eight
      young (6 weeks) with incomplete root development and open apices, and eight adult
      (4 months) with complete root development. One first mandibular molar was
      extracted and whole blood from the alveolar socket collected immediately and at
      5, 10 and 15 min post-extraction. Venous blood samples were collected immediately
      pre- and 24-h post-extraction. All samples were tested for VEGF. RESULTS:
      Increased VEGF levels were found in the venous blood 24 h post-extraction, with a
      significant difference in the young rats (P < 0.05). The increased VEGF serum
      concentration in the young rats was significantly higher (12.2 +/- 4.6 pg ml(-1),
      median 12.1) than that in the adult rats (7.6 +/- 3.8 pg ml(-1), median 6.7) (P =
      0.037). VEGF at the extraction site was not significantly different at 15 min
      post-extraction. At the extraction site, there was no significant difference of
      VEGF concentration between young and adult rats. CONCLUSIONS: Young rats had
      higher post-extraction serum VEGF levels, which may contribute to the healing
      process after dental trauma.

PMID- 18721344
TI  - Wearability and physiological effects of custom-fitted vs self-adapted
      mouthguards.
AB  - OBJECTIVES: The purpose of this study was to measure the comfort, wearability,
      physiological effects and its influence on athletes' physical performance, of
      custom-fitted compared with self-adapted mouthguards (MGs). METHODS: Eleven rugby
      players were put under specific efforts similar to those of the competition. Each
      player made three consecutive tests randomly wearing a commercially available
      'boil-and-bite' self-adapted mouthguard (MG2), a custom-fitted mouthguard (MG3),
      and no mouthguard (reference). Forced expiratory air volume at 1 s (FEV(1)),
      expiratory flow rates peak (PEF), forced vital capacity (FVC), rebound (RB) jump
      15 s, and counter-movement jump (CMJ) were measured on each player before and
      after the training exercise tests. Subjective evaluations by means of a visual
      analog scale (VAS) questionnaire took place. Comforts, adaptability, stability,
      tiredness, thirst, oral dryness, nausea, ability to talk, breathe, and drink were
      evaluated. RESULTS: The wearing of the self-adapted MG showed significant
      improvement in PEF (P < 0.05). There were no statistically significance
      differences regarding the others spirometer parameters. In CMJ, there were no
      differences between both the MGs. On RB power was similar with both MGs and
      control. However, RB height reduced significantly wearing MGs. MG3 showed
      superior properties in comfort, adaptability, stability, and ability to talk and
      to breathe. CONCLUSIONS: MG3 showed the smallest range of changes in players'
      performance, suggesting improved fit, comfort, and acceptation compared with MG2.
      Furthermore, its greatest advantage is the individualized design according to the
      proper anatomy of the oral cavity. Greater efforts must be made to improve the
      comfort of MGs if their use is to be increased.

PMID- 18721346
TI  - Spatial analysis of dental trauma in 12-year-old schoolchildren in Curitiba,
      Brazil.
AB  - The purpose of this study was to build epidemiological indicators on the
      experience of dental trauma in 12-year-old schoolchildren in the city of
      Curitiba, Brazil, exploring its geographical and population distributions. A
      geographic information system (GIS) was used, built by means of ArcView GIS 3.2
      software and geographical databases of streets and districts defined within the
      boundaries of the city of Curitiba, provided by Curitiba's Institute of Research
      and Public Planning (IPPUC). The database used in the study was compiled based on
      an epidemiological survey undertaken in 1998 on a sample of 2126 schoolchildren
      12 years old, residing in outlying urban suburbs distributed over 29 micro-areas
      in the city of Curitiba. The cases selected for this study were those with a
      history of dental trauma, thereby comprising a subsample of 327 schoolchildren.
      The spatial location of the schoolchildren's homes enabled the events to be
      visualized on a cartographic basis. The variables of gender, aetiology of the
      trauma and areas of substandard living conditions were included in the analysis
      and construction of thematic maps, thus making possible a descriptive analysis of
      the spatial distribution of dental trauma in the city. Intra-urban differentials
      were identified in the prevalence of dental trauma in 12-year-old schoolchildren
      in Curitiba. A greater concentration of occurrences was observed in the eastern
      region of the city, especially in areas of substandard living conditions. It was
      possible to conclude that socio-environmental and geophysical factors are
      associated with the determination of dental trauma in the city of Curitiba,
      pointing to the need for the development of public policies especially aimed at
      areas and populations at greater risk.

PMID- 18721345
TI  - An investigation into dentists' management methods of dental trauma to maxillary
      permanent incisors in Victoria, Australia.
AB  - Trauma to anterior teeth in children could become a long-term problem to dental
      health. To a large extent, the management actions of the dentists involved will
      determine the clinical outcome and, in turn, these actions will be related to
      their levels of knowledge. The aim of this study was to investigate dentists'
      knowledge of managing traumatic injuries to maxillary permanent incisors in
      children. A self-completion questionnaire containing 19 questions on management
      methods of treating dental trauma was mailed to 693 dentists in Victoria,
      Australia. The response rate achieved was 61%. This survey found that some of the
      respondents had adequate management knowledge for the different types of
      traumatic injuries, while others did not have the correct information.
      Approximately half the dentists considered milk as the preferred extraoral
      storage medium of choice for avulsed teeth and a period of 7-10 days splinting
      after replantation. A large proportion of dentists showed inadequate knowledge
      with regard to understanding the biological mechanisms causing replacement root
      resorption (61%) and external inflammatory root resorption (74%). Overall, the
      respondents to this survey demonstrated only a moderate level of knowledge in
      management of traumatic injuries to maxillary permanent incisors in children.
      Continuing professional development programmes may be a means of improving this
      deficient knowledge base.

PMID- 18721347
TI  - Biomechanical model of incisor avulsion: a preliminary report.
AB  - The aim of the current study was to produce a two-dimensional finite-element
      model (FEM) of a maxillary incisor being palatally displaced with sufficient
      force to result in avulsion. The viscosity and elastic coefficient of bone were
      chosen from previous studies to model the properties of the periodontal complex.
      A ramped impact of 100 N was applied over a period of 1.5 ms in the direction
      perpendicular to the labial surface of the incisor model. Changes in the
      periodontal ligament (PDL) length (elongation and compression) started
      immediately after the impact and progressed to strain developing in the alveolar
      bone. In accordance with these changes in the PDL length, the tooth started to
      rotate with the center of rotation located at the edge of the palatal alveolar
      bone, combining the stress concentrations at the labial and cervical edges of the
      bone. When the elongation reached the designated limit, PDL disconnection
      occurred, leading to tooth avulsion. The resulting two-dimensional FEM is capable
      of modeling changes in the PDL length and compression, rotation and avulsion.

PMID- 18721348
TI  - Dental trauma among 5th and 6th grade Arab schoolchildren in Eastern Jerusalem.
AB  - Dental trauma is an irreversible pathology which after occurrence is
      characterized by life long debilitating effects. The objective of the study was
      to measure the prevalence of trauma in anterior permanent teeth among children
      and associations with independent variables. A total of 453 5th and 6th grade
      Arab Eastern Jerusalem schoolchildren participated. Trauma, incisal overjet and
      lip competence were measured by one examiner in the schools. Reasons and location
      of trauma were assessed by telephone interviews with the parents. The total
      prevalence of dental trauma was 33.8%. Severe trauma prevalence (involving
      dentine) was 12.6%. Severe trauma was more prevalent among boys (OR = 2.03, P =
      0.026); children with lip incompetence (OR = 2.71, P = 0.001); and those with an
      overjet of 4mm or more (OR = 3.73, P < 0.001). The main reported causes for
      dental trauma were falling (29.1%), sports (16.4%), violence (20%) and playing
      (20%). According to the parents' reports, more fall-related injuries were
      reported at home, more sport injuries at school, more 'playing' injuries
      'outside' (P < 0.001). Combination of results with a previous study among Jewish
      schoolchildren demonstrated: severe dental trauma was related to overjet (OR =
      1.73, P = 0.002), lip incompetence (OR = 2.19, P < 0.001), gender (OR for males =
      1.54, P = 0.005), but not to ethnicity (Arab or Jewish). The reasons for trauma
      observed in this study were potentially preventable. A community effort should
      therefore be pursued, with the aim of educating sports teachers, teachers, health
      personnel and schoolchildren regarding awareness of dental trauma prevention,
      with emphasis on utilizing mouthguards and early orthodontic intervention, when
      financially possible.

PMID- 18721349
TI  - Compliance of children and youngsters in the use of mouthguards.
AB  - The purpose of the study was to examine the compliance of children wearing their
      mouthguards, and to evaluate socio-environmental factors that impact upon the
      usage of the device. Eighty children attending the student clinic of the Hadassah
      School of Dental Medicine received mouthguards free of charge. One year later, 69
      participants and their parents answered a survey aimed at gaining information
      regarding compliance and comfort when wearing the mouthguard correlated with
      gender, ages of parents and child, number of siblings, position of child in the
      family, socio-economic status, education of parents and past dental injuries of
      siblings or parents. Twenty-nine percent of the children never wore the
      mouthguard, 32% wore it sometimes, 15.9% wore it when necessary at the beginning
      but stopped after one month and 23.2% wore the mouthguard whenever needed. About
      68% of the participants still possessed the mouthguard one year after receiving
      it, 44.9% reported that they did not wear the mouthguard because they forgot and
      42% reported that the reason for not wearing the appliance was because it was not
      comfortable. Seventy-seven percent of the parents were not aware of the existence
      of this appliance prior to this study. In addition, 47.9% stated that dentists
      had not offered such treatment to them in the past, 20.8% indicated that their
      child had never possessed a mouthguard before due to its significant expense and
      39.6% stated that they would not invest in this treatment in the future because
      their child would not wear the appliance. Boys were more comfortable wearing the
      mouthguard than girls. The younger the child and the later s/he was in the
      sibling order of the family, the more likely s/he was to lose the mouthguard.

PMID- 18721350
TI  - Incidence and pattern of mandibular fractures in rural population: a review of
      324 patients at a tertiary hospital in Loni, Maharashtra, India.
AB  - The aim of this study was to document the pattern and incidence of mandibular
      fractures occurring in rural population, at Rural Dental College and Hospital,
      Maharashtra, India. A retrospective analysis of patient records and radiographs
      for the 5-year period from January 2003 to December 2007 was conducted. Data were
      identified and analyzed based on age group, gender distribution, anatomic
      location, and cause of injury. A total of 324 patients with 486 injuries were
      reviewed, males formed 80.9% and females 19.1% of the studied population, with
      peak incidence occurring in the 21-30 years age group. The most common fractures
      site was parasymphysis (39.3%). The etiology of mandibular fractures was road
      traffic accidents (42.9%), followed by falls (25.9%), assaults and interpersonal
      violence (20.7%), and animal injuries (10.5%). Our results exhibit that road
      traffic accidents remain the major cause of mandibular trauma and animal injuries
      being found exclusively in rural population. There is a variation of incidence
      and pattern of maxillofacial trauma from region to region.

PMID- 18721351
TI  - Pattern of traumatic dental injuries in children attending the University Dental
      Hospital, Sri Lanka.
AB  - AIM: The aim of this study was to determine the pattern of traumatic dental
      injuries in children seeking care at the Division of Paediatric Dentistry, the
      Dental Hospital, University of Peradeniya, Sri Lanka. MATERIAL AND METHODS: The
      sample consisted of patients attending the Division Paediatric Dentistry,
      University Dental Hospital for traumatic dental injuries between February 2003
      and May 2006. The data were collected by means of an interviewer administered
      questionnaire to parent/guardian and a clinical examination. RESULTS: A total of
      197 children aged between 2 and 17 years had sought treatment for 304 traumatized
      teeth. Half of the patients had sought treatment more than 1 month after the
      trauma occurred. The most frequent cause for dental trauma was a fall (89%)
      whilst compromised aesthetics was the most common reason for seeking care (48%).
      Maxillary central incisors were the most affected teeth. Of the permanent teeth,
      49% had sustained uncomplicated fractures involving only the enamel and dentine.
      Pulp therapy ranging from pulpotomy to root canal treatment was the treatment of
      choice for most of the traumatized permanent teeth (46%). In the deciduous teeth,
      a fracture involving enamel, dentine and the pulp was the most common (35%).
      CONCLUSIONS: As there was a considerable delay in seeking care for these
      injuries, it is recommended that educational programs be conducted for parents to
      create awareness about the importance of immediate management of traumatized
      teeth.

PMID- 18721352
TI  - A modified method of mouthguard fabrication for orthodontic patients.
AB  - Orthodontic appliances are one of the major risk factors for traumatic injuries
      during sports events. As it is difficult to take precise impressions with
      orthodontic appliances, fabricated custom-made mouthguards (MGs) often have poor
      retention or are too tight causing the disturbance of orthodontic treatments. The
      purpose of this article is to describe a method for custom-made MG fabrication
      using sheet and tube materials, with which better MG retention and rigidity as
      well as pressure control to the orthodontic appliances can be easily achieved.

PMID- 18721353
TI  - Avulsion of permanent lower central incisors: esthetic-functional solution.
AB  - This short communication reports a clinical case of a 11-year-old girl, who
      underwent an avulsion of the lower left lateral incisor and who sought delayed
      treatment. The treatment was a combined technique with polyethylene fibers and
      composite resins to create a fixed partial denture, which is a low-cost solution
      and presents a good esthetic-functional result. The technique is described and
      the success of its use in appropriately recommended cases is confirmed.

PMID- 18721354
TI  - Multidisciplinary approach of complicated crown fractures of both superior
      central incisors: a case report.
AB  - Anterior crown fractures are a common form of traumatic dental injuries that
      mainly affect the maxillary central incisors, in children and teenagers. Since
      the development of the adhesive dentistry, many case reports of crown fractures
      restored using adhesive reattachment techniques were published. Complex cases, in
      which more than one tooth are involved, with fractures differing from each other,
      require specific treatment of each fracture, taking different advantages of the
      different remaining tooth structures. This case report describes a patient with
      dissimilar crown fractures of both superior central incisors. After the
      endodontic treatment, the patient was treated using the combination of several
      techniques: periodontal surgery (crown lengthening with apically repositioned
      flap and osseous resective surgery), adhesive technique and cast restoration plus
      esthetic crown. The periodontal procedure re-created the biologic width and
      proved to be a reliable adjunctive procedure to the adhesive and the prosthetic
      techniques used.

PMID- 18721355
TI  - Tooth fragments lodged in the lower lip after traumatic dental injury: a case
      report.
AB  - Dental fractures are common trauma complications in the oral cavity. The
      efficient diagnosis and treatment of dental injury are important elements in
      clinical dentistry. This article describes a case study of trauma in central
      maxillary incisors with tooth fragments lodged in the lower lip. Radiographs of
      the soft structures proved themselves as an important tool in the detection and
      identification of occult tooth fragments, and play an important role in the
      establishment of the treatment to be adopted. Also, case follow-up is of
      fundamental significance in the preservation and maintenance of compromised
      structures.

PMID- 18721356
TI  - Idiopathic root resorption of the entire permanent dentition: systematic review
      and report of a case.
AB  - A rare case of idiopathic root resorption affecting the entire dentition was
      described. Root resorptions of all of the maxillary and mandibular teeth were
      coincidentally diagnosed on patient's radiographic examination. The patient's
      medical and dental findings were non-contributory, other than the increased
      mobility of upper incisors. No significant familial findings could be identified.
      Detailed radiographic examination revealed resorption affecting the apical part
      of the roots, resulting in vertical shortening of the teeth. The character of the
      resorption was as if a tapering occurred throughout the lateral root surfaces.
      Involved teeth were endodontically treated and the patient was subsequently
      followed-up for 18 months. Following endodontic therapy, all periapical lesions
      demonstrated clinical and radiographic evidence of healing. Endodontic therapy
      resulted in a high degree of success to stop resorption process and maintain the
      dentition.

PMID- 18721358
TI  - Efforts to expand physician supply deserve scrutiny.

PMID- 18721361
TI  - Abstracts of the 6th World Stroke Congress and Xth International Symposium on
      Thrombolysis and Acute Stroke Therapy. September 24-27, 2008 Vienna, Austria and
      September 21-23, 2008, Budapest, Hungary.

PMID- 18721397
TI  - Measuring the effectiveness of dietetic interventions in nutritional support.

PMID- 18721398
TI  - Personalized nutrition for the prevention of cardiovascular disease: a future
      perspective.
AB  - Cardiovascular disease (CVD) is responsible for significant morbidity and
      mortality in the Western and developing world. This multi-factorial disease is
      influenced by many environmental and genetic factors. At present, public health
      advice involves prescribed population-based recommendations, which have been
      largely unsuccessful in reducing CVD risk. This is, in part, due to individual
      variability in response to dietary manipulations, that arises from nutrient-gene
      interactions (defined by the term 'nutrigenetics'). The shift towards
      personalized nutritional advice is a very attractive proposition, where, in
      principle, an individual can be given dietary advice specifically tailored to
      their genotype. However, the evidence-base for the impact of interactions between
      nutrients and fixed genetic variants on biomarkers of CVD risk is still very
      limited. This paper reviews the evidence for interactions between dietary fat and
      two common polymorphisms in the apolipoprotein E and peroxisome proliferator
      activated receptor-gamma genes. Although an increased understanding of how these
      and other genes influence response to nutrients should facilitate the progression
      of personalized nutrition, the ethical issues surrounding its routine use need
      careful consideration.

PMID- 18721399
TI  - Does taking vitamin, mineral and fatty acid supplements prevent cognitive
      decline? A systematic review of randomized controlled trials.
AB  - BACKGROUND: Observational studies have shown associations between nutritional
      status and cognition in later life but evidence from intervention studies is
      unclear. The present study systematically reviewed the evidence on the effect of
      nutrient supplementation on cognitive function in people aged >or=65 years.
      METHODS: Databases including MEDLINE and EMBASE were searched up to 1 September
      2006. Randomized controlled trials using at least one kind of vitamin, mineral or
      omega-3 fatty acid, evaluating standardized neuropsychological test(s), were
      included. There were no restrictions on participants' baseline nutritional status
      or cognitive function. Quality assessment and data abstraction were conducted by
      one author and checked by another. RESULTS: Of 4229 articles retrieved, 22 trials
      (3442 participants) were identified. Many were small, short duration and of poor
      methodology. Only 16 out of 122 cognitive tests were significantly different
      between groups. A meta-analysis showed no significant effect of taking B vitamins
      or antioxidant vitamins on global cognitive function. There was insufficient
      evidence to evaluate the effect of omega-3 fatty acids on any cognitive domains.
      CONCLUSION: There was little evidence of a beneficial effect from taking B
      vitamins or antioxidant supplements on global cognitive function in later life.
      Larger-scale randomized controlled trials of longer duration in selected age
      groups are needed.

PMID- 18721400
TI  - An retrospective audit of patients with polycystic ovary syndrome: the effects of
      a reduced glycaemic load diet.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism
      and chronic anovulation. The aim of this retrospective audit was to determine the
      patient profile, including anthropometrics, biochemistry and symptoms, and to
      evaluate the influence of a dietary intervention in women with PCOS. METHODS:
      Data were collected retrospectively from dietetic and medical records from all
      PCOS patients (n = 88) who attended a dietetic consultation from July 2004 to
      July 2006. As standard clinic practice, a reduced glycaemic load diet had been
      prescribed, with energy reduction in overweight patients. Follow-up data were
      available for 59 patients. RESULTS: Fifty-eight patients had a body mass index
      (BMI) <or= 24.9 kg m(-2) and 30 had a BMI >or= 25 kg m(-2). Thirty-six patients,
      with a BMI <or= 24.9 kg m(-2), self-reported central weight gain at their initial
      appointment. Over two-thirds of patients self-reported one or more of the
      following symptoms: carbohydrate cravings, hypoglycaemia, tiredness and hunger.
      At the follow-up appointment, BMI and waist circumference significantly decreased
      in overweight patients (P < 0.05). Seventy-one percent of women self-reported
      hypoglycaemia initially; this was reduced to 13% at follow-up (P < 0.01).
      CONCLUSIONS: The audit indicated a low glycaemic load diet in combination with
      medication may contribute to an improvement in symptom relief in patients with
      PCOS.

PMID- 18721401
TI  - Diet quality of persons living with HIV/AIDS on highly active antiretroviral
      therapy.
AB  - BACKGROUND: This study sought to assess the diet quality of individuals living
      with HIV/AIDS who were receiving antiretroviral therapy in Sao Paulo, Brazil.
      METHODS: This cross-sectional study involved 56 HIV-infected adults. Demographic
      and anthropometric data were collected, and diet quality was measured using the
      Healthy Eating Index (HEI), modified for Brazilians, which included ten
      components: adequacy of intake of six different food groups, total fat,
      cholesterol, dietary fibre and dietary variety. RESULTS: Among the individuals
      assessed, 64.3% of the participants had a diet needing improvement, while 8.7%
      had a poor diet. The overall HEI score was 68.3 points (SD = 14.9). Mean scores
      were low for fruits, vegetables, dairy products and dietary fibre; and high for
      meats and eggs, total fat and cholesterol. The overall HEI score was higher among
      individuals who were not overweight (P = 0.003), who were also more likely to
      achieve dietary goals for dairy products (P = 0.039) and grains (P = 0.005).
      CONCLUSION: Most of these adults living with HIV/AIDS had diets that required
      improvement, and being overweight was associated with poorer diet quality.
      Nutritional interventions aimed at maintaining healthy body weight and diet
      should be taken into account in caring for HIV-infected people.

PMID- 18721402
TI  - Does maternal knowledge and parent education affect blood phenylalanine control
      in phenylketonuria?
AB  - BACKGROUND: Metabolic control in phenylketonuria (PKU) may be influenced by
      parental ability because dietary treatment involves complex food choices. This is
      an observational study to compare maternal carer (MC) knowledge and parental
      education with phenylalanine concentrations in children with PKU. METHODS:
      Children (n = 46; 26 boys) aged 1-10 years (median age 6 years) on dietary
      treatment were recruited. Their median lifetime and median phenylalanine
      concentrations in the year prior to study were estimated. MC completed a
      questionnaire to assess dietary knowledge. RESULTS: Overall maternal knowledge on
      most aspects of diet was good and there was a correlation between annual median
      blood phenylalanine concentrations, but at the age of 5-6 years of age only, and
      higher maternal carer scores on PKU knowledge (r = -0.646; P < 0.0001). Three of
      only four children (12%) with median phenylalanine concentrations above 500
      micromol L(-1) in the year prior to study had both parents leave school without
      educational qualifications. Children who had median phenylalanine concentrations
      (n = 3; 7%) over the recommended ranges at 3 years of age or earlier continued to
      have poor control. CONCLUSIONS: Blood phenylalanine control within the first 3
      years of age, poor parental educational achievement at school level, and
      unsatisfactory maternal dietary knowledge may all influence longer-term blood
      phenylalanine control in children.

PMID- 18721454
TI  - Breast cancer, psychological distress and life events among young women.
AB  - Since 1983, studies have suggested an interaction between the severe life events,
      psychological distress and the etiology of Cancer. However, these associations
      are still under dispute. The aim of the present study was to examine the
      relationship between life events, psychological distress and Breast Cancer (BC)
      among young women. METHODS: A case control study. The study population included
      622 women, under the age of 45 years. 255 were diagnosed for BC, and 367 were
      healthy women. A validated Brief Symptom Inventory (BSI) and Life Event
      Questionnaire were used. RESULTS: The cases presented significantly higher scores
      of depression compared to the controls and significant lower scores of happiness
      and optimism. A significant difference was found when comparing the groups
      according to the cumulative number of life events (two or more events). A
      multivariate analysis suggest that exposure to more than one life event is
      positively associated with BC [Odds Ratio(OR) :1.62 95% Confidence Interval (CI):
      1.09-2.40], and that a general feeling of happiness and optimism has a
      "protective effect" on the etiology of BC. (OR-0.75, 95% CI:0.64-0.86).
      CONCLUSION: Young women who were exposed to a number of life events, should be
      considered as a risk group for BC and treated accordingly.

PMID- 18721453
TI  - Early life environment and snoring in adulthood.
AB  - BACKGROUND: To our knowledge, no studies of the possible association of early
      life environment with snoring in adulthood have been published. We aimed to
      investigate whether early life environment is associated with snoring later in
      life. METHODS: A questionnaire including snoring frequency in adulthood and
      environmental factors in early life was obtained from 16,190 randomly selected
      men and women, aged 25-54 years, in Sweden, Norway, Iceland, Denmark and Estonia
      (response rate 74%). RESULTS: A total of 15,556 subjects answered the questions
      on snoring. Habitual snoring, defined as loud and disturbing snoring at least 3
      nights a week, was reported by 18%. Being hospitalized for a respiratory
      infection before the age of two years (adjusted odds ratio (OR) = 1.27; 95%
      confidence interval (CI) 1.01-1.59), suffering from recurrent otitis as a child
      (OR = 1.18; 95%CI 1.05-1.33), growing up in a large family (OR = 1.04; 95%CI
      1.002-1.07) and being exposed to a dog at home as a newborn (OR = 1.26; 95%CI
      1.12-1.42) were independently related to snoring later in life and independent of
      a number of possible confounders in adulthood. The same childhood environmental
      factors except household size were also related with snoring and daytime
      sleepiness combined. CONCLUSION: The predisposition for adult snoring may be
      partly established early in life. Having had severe airway infections or
      recurrent otitis in childhood, being exposed to a dog as a newborn and growing up
      in a large family are environmental factors associated with snoring in adulthood.

PMID- 18721452
TI  - Identification of intra-group, inter-individual, and gene-specific variances in
      mRNA expression profiles in the rheumatoid arthritis synovial membrane.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive
      joint disease characterized by overexpression of pro-inflammatory/pro-destructive
      genes and other activating genes (for example, proto-oncogenes) in the synovial
      membrane (SM). The gene expression in disease is often characterized by
      significant inter-individual variances via specific
      synchronization/desynchronization of gene expression. To elucidate the
      contribution of the variance to the pathogenesis of disease, expression variances
      were tested in SM samples of RA patients, osteoarthritis (OA) patients, and
      normal controls (NCs). METHOD: Analysis of gene expression in RA, OA, and NC
      samples was carried out using Affymetrix U133A/B oligonucleotide arrays, and the
      results were validated by real-time reverse transcription-polymerase chain
      reaction. For the comparison between RA and NC, 568 genes with significantly
      different variances in the two groups (P <or= 0.05; Bonferroni/Holm corrected
      Brown-Forsythe version of the Levene test) were selected. For the comparison
      between RA and OA, 333 genes were selected. By means of the Kyoto Encyclopedia of
      Genes and Genomes, the pathways/complexes significantly affected by higher gene
      expression variances were identified in each group. RESULTS: Ten
      pathways/complexes significantly affected by higher gene expression variances
      were identified in RA compared with NC, including cytokine-cytokine receptor
      interactions, the transforming growth factor-beta pathway, and anti-apoptosis.
      Compared with OA, three pathways with significantly higher variances were
      identified in RA (for example, B-cell receptor signaling and vascular endothelial
      growth factor signaling). Functionally, the majority of the identified pathways
      are involved in the regulation of inflammation, proliferation, cell survival, and
      angiogenesis. CONCLUSION: In RA, a number of disease-relevant or even disease
      specific pathways/complexes are characterized by broad intra-group inter
      individual expression variances. Thus, RA pathogenesis in different individuals
      may depend to a lesser extent on common alterations of the expression of specific
      key genes, and rather on individual-specific alterations of different genes
      resulting in common disturbances of key pathways.

PMID- 18721455
TI  - An evaluation of a Shockroom located CT scanner: a randomized study of early
      assessment by CT scanning in trauma patients in the bi-located trauma center
      North-West Netherlands (REACT trial).
AB  - BACKGROUND: Trauma is a major source of morbidity and mortality, especially in
      people below the age of 50 years. For the evaluation of trauma patients CT
      scanning has gained wide acceptance in and provides detailed information on
      location and severity of injuries. However, CT scanning is frequently time
      consuming due to logistical (location of CT scanner elsewhere in the hospital)
      and technical issues. An innovative and unique infrastructural change has been
      made in the AMC in which the CT scanner is transported to the patient instead of
      the patient to the CT scanner. As a consequence, early shockroom CT scanning
      provides an all-inclusive multifocal diagnostic modality that can detect
      (potentially life-threatening) injuries in an earlier stage, so that therapy can
      be directed based on these findings. METHODS/DESIGN: The REACT-trial is a
      prospective, randomized trial, comparing two Dutch level-1 trauma centers,
      respectively the VUmc and AMC, with the only difference being the location of the
      CT scanner (respectively in the Radiology Department and in the shockroom). All
      trauma patients that are transported to the AMC or VUmc shockroom according to
      the current prehospital triage system are included. Patients younger than 16
      years of age and patients who die during transport are excluded. Randomization
      will be performed prehospitally. Study parameters are the number of days outside
      the hospital during the first year following the trauma (primary outcome),
      general health at 6 and 12 months post trauma, mortality and morbidity, and
      various time intervals during initial evaluation. In addition a cost
      effectiveness analysis of this shockroom concept will be performed. Regarding
      primary outcome it is estimated that the common standard deviation of days spent
      outside of the hospital during the first year following trauma is a total of 12
      days. To detect an overall difference of 2 days within the first year between the
      two strategies, 562 patients per group are needed. (alpha 0.95 and beta 0.80).
      DISCUSSION: The REACT-trial will provide evidence on the effects of a strategy
      involving early shockroom CT scanning compared with a standard diagnostic imaging
      strategy in trauma patients on both patient outcome and operations research.
      TRIAL REGISTRATION: ISRCTN55332315.

PMID- 18721456
TI  - Prognostic value of brain natriuretic peptide in acute pulmonary embolism.
AB  - INTRODUCTION: The relationship between brain natriuretic peptide (BNP) increase
      in acute pulmonary embolism (PE) and the increase in mortality and morbidity has
      frequently been suggested in small studies but its global prognostic performance
      remains largely undefined. We performed a systematic review and meta-analysis of
      data to examine the prognostic value of elevated BNP for short-term all-cause
      mortality and serious adverse events. METHODS: The authors reviewed PubMed,
      BioMed Central, and the Cochrane database and conducted a manual review of
      article bibliographies. Using a prespecified search strategy, we included a study
      if it used BNP or N-terminal pro-BNP biomarkers as a diagnostic test in patients
      with documented PE and if it reported death, the primary endpoint of the meta
      analysis, in relation to BNP testing. Studies were excluded if they were
      performed in patients without certitude of PE or in a subset of patients with
      cardiogenic shock. Twelve relevant studies involving a total of 868 patients with
      acute PE at baseline were included in the meta-analysis using a random-effects
      model. RESULTS: Elevated BNP levels were significantly associated with short-term
      all-cause mortality (odds ratio [OR] 6.57, 95% confidence interval [CI] 3.11 to
      13.91), with death resulting from PE (OR 6.10, 95% CI 2.58 to 14.25), and with
      serious adverse events (OR 7.47, 95% CI 4.20 to 13.15). The corresponding
      positive and negative predictive values for death were 14% (95% CI 11% to 18%)
      and 99% (95% CI 97% to 100%), respectively. CONCLUSION: This meta-analysis
      indicates that, while elevated BNP levels can help to identify patients with
      acute PE at high risk of death and adverse outcome events, the high negative
      predictive value of normal BNP levels is certainly more useful for clinicians to
      select patients with a likely uneventful follow-up.

PMID- 18721457
TI  - The M18 aspartyl aminopeptidase of Plasmodium falciparum binds to human
      erythrocyte spectrin in vitro.
AB  - BACKGROUND: During erythrocytic schizogony, Plasmodium falciparum interacts with
      the human erythrocyte membrane when it enters into, grows within and escapes from
      the erythrocyte. An interaction between the P. falciparum M18 aspartyl
      aminopeptidase (PfM18AAP) and the human erythrocyte membrane protein spectrin was
      recently identified using phage display technology. In this study, recombinant
      (r) PfM18AAP was characterized and the interaction between the enzyme and
      spectrin, as well as other erythrocyte membrane proteins, analyzed. METHODS:
      rPfM18AAP was produced as a hexahistidine-fusion protein in Escherichia coli and
      purified using magnetic bead technology. The pI of the enzyme was determined by
      two-dimensional gel electrophoresis and the number of subunits in the native
      enzyme was estimated from Ferguson plots. The enzymatic activity over a pH and
      temperature range was tested by a coupled enzyme assay. Blot overlays were
      performed to validate the spectrin-PfM18AAP interaction, as well as identify
      additional interactions between the enzyme and other erythrocyte membrane
      proteins. Sequence analysis identified conserved amino acids that are expected to
      be involved in cofactor binding, substrate cleavage and quaternary structure
      stabilization. RESULTS: rPfM18AAP has a molecular weight of ~67 kDa and the
      enzyme separated as three entities with pI 6.6, 6.7 and 6.9. Non-denaturing gel
      electrophoresis indicated that rPfM18AAP aggregated into oligomers. An in vitro
      coupled enzyme assay showed that rPfM18AAP cleaved an N-terminal aspartate from a
      tripeptide substrate with maximum enzymatic activity at pH 7.5 and 37 degrees C.
      The spectrin-binding region of PfM18AAP is not found in Homo sapiens,
      Saccharomyces cerevisiae and otherPlasmodium species homologues. Amino acids
      expected to be involved in cofactor binding, substrate cleavage and quaternary
      structure stabilization, are conserved. Blot overlays with rPfM18AAP against
      spectrin and erythrocyte membrane proteins indicated that rPfM18AAP binds to
      spectrin, as well as to protein 4.1, protein 4.2, actin and glyceraldehyde 3
      phosphate dehydrogenase. CONCLUSION: Studies characterizing rPfM18AAP showed that
      this enzyme interacts with erythrocyte spectrin and other membrane proteins. This
      suggests that, in addition to its proposed role in hemoglobin digestion, PfM18AAP
      performs other functions in the erythrocyte host and can utilize several
      substrates, which highlights the multifunctional role of malaria enzymes.

PMID- 18721458
TI  - A single site for N-linked glycosylation in the envelope glycoprotein of feline
      immunodeficiency virus modulates the virus-receptor interaction.
AB  - Feline immunodeficiency virus (FIV) targets helper T cells by attachment of the
      envelope glycoprotein (Env) to CD134, a subsequent interaction with CXCR4 then
      facilitating the process of viral entry. As the CXCR4 binding site is not exposed
      until CD134-binding has occurred then the virus is protected from neutralising
      antibodies targeting the CXCR4-binding site on Env. Prototypic FIV vaccines based
      on the FL4 strain of FIV contain a cell culture-adapted strain of FIV Petaluma, a
      CD134-independent strain of FIV that interacts directly with CXCR4. In addition
      to a characteristic increase in charge in the V3 loop homologue of FIVFL4, we
      identified two mutations in potential sites for N-linked glycosylation in the
      region of FIV Env analogous to the V1-V2 region of HIV and SIV Env, T271I and
      N342Y. When these mutations were introduced into the primary GL8 and CPG41
      strains of FIV, the T271I mutation was found to alter the nature of the virus
      CD134 interaction; primary viruses carrying the T271I mutation no longer required
      determinants in cysteine-rich domain (CRD) 2 of CD134 for viral entry. The T271I
      mutation did not confer CD134-independent infection upon GL8 or CPG41, nor did it
      increase the affinity of the CXCR4 interaction, suggesting that the principal
      effect was targeted at reducing the complexity of the Env-CD134 interaction.

PMID- 18721459
TI  - Catalogue of epidermal genes: genes expressed in the epidermis during larval molt
      of the silkworm Bombyx mori.
AB  - BACKGROUND: The insect cuticle is composed of various proteins and formed during
      the molt under hormonal regulation, although its precise composition and
      formation mechanism are largely unknown. The exhaustive catalogue of genes
      expressed in epidermis at the molt constitutes a massive amount of information
      from which to draw a complete picture of the molt and cuticle formation in
      insects. Therefore, we have catalogued a library of full-length cDNAs (designated
      epM) from epidermal cells during the last larval molt of Bombyx mori. RESULTS: Of
      the 10,368 sequences in the library, we isolated 6,653 usable expressed sequence
      tags (ESTs), which were categorized into 1,451 nonredundant gene clusters.
      Seventy-one clusters were considered to be isoforms or premature forms of other
      clusters. Therefore, we have identified 1,380 putative genes. Of the 6,653
      expressed sequences, 48% were derived from 92 cuticular protein genes (RR-1, 24;
      RR-2, 17; glycine-rich, 29; other classes, 22). A comparison of epM with another
      epidermal EST data set, epV3 (feeding stage: fifth instar, day 3), showed marked
      differences in cuticular protein gene. Various types of cuticular proteins are
      expressed in epM but virtually only RR-1 proteins were expressed in epV3.
      Cuticular protein genes expressed specifically in epidermis, with several types
      of expression patterns during the molt, suggest different types of responses to
      the ecdysteroid pulse. Compared with other Bombyx EST libraries, 13 genes were
      preferentially included in epM data set. We isolated 290 genes for proteins other
      than cuticular proteins, whose amino acid sequences retain putative signal
      peptides, suggesting that they play some role in cuticle formation or in other
      molting events. Several gene groups were also included in this data set: hormone
      metabolism, P450, modifier of cuticular protein structure, small-ligand-binding
      protein, transcription factor, and pigmentation genes. CONCLUSION: We have
      identified 1,380 genes in epM data set and 13 preferentially expressed genes in
      epidermis at the molt. The comparison of the epM and other EST libraries
      clarified the totally different gene expression patterns in epidermis between the
      molting and feeding stages and many novel tissue- and stage-specifically
      expressed epidermal genes. These data should further our understanding of cuticle
      formation and the insect molt.

PMID- 18721462
TI  - Primary squamous cell carcinoma of lung in a 13-year-old boy: a case report.
AB  - We are reporting a very rare case of primary bronchogenic squamous cell
      carcinoma (SCC) with bone metastasis in a 13-year-old boy. A brief review of the
      English literature on this rare neoplasm in childhood is presented.

PMID- 18721460
TI  - Evolution of developmental roles of Pax2/5/8 paralogs after independent
      duplication in urochordate and vertebrate lineages.
AB  - BACKGROUND: Gene duplication provides opportunities for lineage diversification
      and evolution of developmental novelties. Duplicated genes generally either
      disappear by accumulation of mutations (nonfunctionalization), or are preserved
      either by the origin of positively selected functions in one or both duplicates
      (neofunctionalization), or by the partitioning of original gene subfunctions
      between the duplicates (subfunctionalization). The Pax2/5/8 family of important
      developmental regulators has undergone parallel expansion among chordate groups.
      After the divergence of urochordate and vertebrate lineages, two rounds of
      independent gene duplications resulted in the Pax2, Pax5, and Pax8 genes of most
      vertebrates (the sister group of the urochordates), and an additional duplication
      provided the pax2a and pax2b duplicates in teleost fish. Separate from the
      vertebrate genome expansions, a duplication also created two Pax2/5/8 genes in
      the common ancestor of ascidian and larvacean urochordates. RESULTS: To better
      understand mechanisms underlying the evolution of duplicated genes, we
      investigated, in the larvacean urochordate Oikopleura dioica, the embryonic gene
      expression patterns of Pax2/5/8 paralogs. We compared the larvacean and ascidian
      expression patterns to infer modular subfunctions present in the single pre
      duplication Pax2/5/8 gene of stem urochordates, and we compared vertebrate and
      urochordate expression to infer the suite of Pax2/5/8 gene subfunctions in the
      common ancestor of olfactores (vertebrates + urochordates). Expression pattern
      differences of larvacean and ascidian Pax2/5/8 orthologs in the endostyle,
      pharynx and hindgut suggest that some ancestral gene functions have been
      partitioned differently to the duplicates in the two urochordate lineages. Novel
      expression in the larvacean heart may have resulted from the neofunctionalization
      of a Pax2/5/8 gene in the urochordates. Expression of larvacean Pax2/5/8 in the
      endostyle, in sites of epithelial remodeling, and in sensory tissues evokes like
      functions of Pax2, Pax5 and Pax8 in vertebrate embryos, and may indicate ancient
      origins for these functions in the chordate common ancestor. CONCLUSION:
      Comparative analysis of expression patterns of chordate Pax2/5/8 duplicates,
      rooted on the single-copy Pax2/5/8 gene of amphioxus, whose lineage diverged
      basally among chordates, provides new insights into the evolution and development
      of the heart, thyroid, pharynx, stomodeum and placodes in chordates; supports the
      controversial conclusion that the atrial siphon of ascidians and the otic placode
      in vertebrates are homologous; and backs the notion that Pax2/5/8 functioned in
      ancestral chordates to engineer epithelial fusions and perforations, including
      gill slit openings.

PMID- 18721463
TI  - Protective ventilation in ARDS: as soon as possible. An immediate use of HFOV.
AB  - OBJECTIVE: To report the immediate use of High-Frequency Oscillatory ventilation
      in an adult acute respiratory distress syndrome. DESIGN: Case report. SETTING:
      Intensive care unit at the Military Teaching Hospital of Toulon. PATIENT: A 64-yr
      old Caucasian male who developed acute respiratory distress syndrome in the
      course of severe falciparum malaria. INTERVENTION: Initial use of HFO to minimise
      ventilator-induced lung injury. MEASUREMENT AND MAIN RESULTS: Rapid improvement
      of PaO2/fraction of inspired oxygen from 172 mmHg (NIV) to 310 mmHg with HFO. No
      ventilator-induced injury on CT scan after 5 days of invasive ventilation.
      CONCLUSION: In contrast with previous studies, we successfully used lung
      protective ventilation with HFO immediately. Further studies, with immediate,
      rather than rescue use of HFO ventilation, are needed.

PMID- 18721461
TI  - Differential screening identifies transcripts with depot-dependent expression in
      white adipose tissues.
AB  - BACKGROUND: The co-morbidities of obesity are tied to location of excess fat in
      the intra-abdominal as compared to subcutaneous white adipose tissue (WAT) depot.
      Genes distinctly expressed in WAT depots may impart depot-dependent physiological
      functions. To identify such genes, we prepared subtractive cDNA libraries from
      murine subcutaneous (SC) or intra-abdominal epididymal (EP) white adipocytes.
      RESULTS: Differential screening and qPCR validation identified 7 transcripts with
      2.5-fold or greater enrichment in EP vs. SC adipocytes. Boc, a component of the
      hedgehog signaling pathway demonstrated highest enrichment (approximately 12
      fold) in EP adipocytes. We also identified a dramatic enrichment in SC adipocytes
      vs. EP adipocytes and in SC WAT vs. EP WAT for transcript(s) for the major
      urinary proteins (Mups), small secreted proteins with pheromone functions that
      are members of the lipocalin family. Expression of Boc and Mup transcript was
      further assessed in murine tissues, adipogenesis models, and obesity. qPCR
      analysis reveals that EP WAT is a major site of expression of Boc transcript.
      Furthermore, Boc transcript expression decreased in obese EP WAT with a
      concomitant upregulation of Boc transcript in the obese SC WAT depot. Assessment
      of the Boc binding partner Cdon in adipose tissue and cell fractions thereof,
      revealed transcript expression similar to Boc; suggestive of a role for the Boc
      Cdon axis in WAT depot function. Mup transcripts were predominantly expressed in
      liver and in the SC and RP WAT depots and increased several thousand-fold during
      differentiation of primary murine preadipocytes to adipocytes. Mup transcripts
      were also markedly reduced in SC WAT and liver of ob/ob genetically obese mice
      compared to wild type. CONCLUSION: Further assessment of WAT depot-enriched
      transcripts may uncover distinctions in WAT depot gene expression that illuminate
      the physiological impact of regional adiposity.

PMID- 18721464
TI  - Chemogenetic fingerprinting by analysis of cellular growth dynamics.
AB  - BACKGROUND: A fundamental goal in chemical biology is the elucidation of on- and
      off-target effects of drugs and biocides. To this aim chemogenetic screens that
      quantify drug induced changes in cellular fitness, typically taken as changes in
      composite growth, is commonly applied. RESULTS: Using the model organism
      Saccharomyces cerevisiae we here report that resolving cellular growth dynamics
      into its individual components, growth lag, growth rate and growth efficiency,
      increases the predictive power of chemogenetic screens. Both in terms of drug
      drug and gene-drug interactions did the individual growth variables capture
      distinct and only partially overlapping aspects of cell physiology. In fact, the
      impact on cellular growth dynamics represented functionally distinct chemical
      fingerprints. DISCUSSION: Our findings suggest that the resolution and
      quantification of all facets of growth increases the informational and
      interpretational output of chemogenetic screening. Hence, by facilitating a
      physiologically more complete analysis of gene-drug and drug-drug interactions
      the here reported results may simplify the assignment of mode-of-action to orphan
      bioactive compounds.

PMID- 18721467
TI  - HIV/AIDS awareness and risk behaviour among pregnant women in Semey, Kazakhstan,
      2007.
AB  - BACKGROUND: Central Asia has one of the most rapidly increasing HIV prevalence in
      the world. The aim of this study was to evaluate current knowledge, risk
      behaviour and attitudes to voluntary counselling and testing concerning HIV/AIDS
      among pregnant women in Semey, Kazakhstan. METHODS: We collected 226
      questionnaires in a consecutive sample from a population on 520 pregnant women.
      The results were related to ethnicity, age and education level. RESULTS: Ninety
      six percent had heard about HIV. Positive findings were that 89% and 86% of the
      women were aware of the two main routes of transmission: sexual intercourses
      without a condom and sharing needles while injecting drugs. The women had first
      heard about HIV/AIDS through the media with, 52%, and at school with 40%. Only
      46% and 68% of the women pointed out breastfeeding and mother-to-child
      transmission during pregnancy or delivery as routes of transmission. Eighty-three
      percent were prepared not to breastfeed their baby if they were found to be HIV
      positive. Slightly more, 86%, accepted the need to take medicine, but fewer
      women, 68%, were positive to Caesarean section. Negative findings were that only
      28% answered that there are ways to protect oneself against sexually transmitted
      HIV/AIDS and specified that this was condom use. CONCLUSION: The pregnant women
      in Semey have poor knowledge about specific mother-to-child HIV transmission and
      do not know about the means of reducing mother-to-child HIV infection. The
      information in the public health program needs to be improved. However, most of
      the women in Semey were positive to prevention strategies for mother-to-child
      transmission after hearing about it.

PMID- 18721465
TI  - Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in
      Crohn's disease: a randomized multicenter trial (LIR!C-trial).
AB  - BACKGROUND: With the availability of infliximab, nowadays recurrent Crohn's
      disease, defined as disease refractory to immunomodulatory agents that has been
      treated with steroids, is generally treated with infliximab. Infliximab is an
      effective but expensive treatment and once started it is unclear when therapy can
      be discontinued. Surgical resection has been the golden standard in recurrent
      Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is
      characterized by a quick symptom reduction. The objective of this study is to
      compare infliximab treatment with laparoscopic ileocolic resection in patients
      with recurrent Crohn's disease of the distal ileum with respect to quality of
      life and costs. METHODS/DESIGN: The study is designed as a multicenter randomized
      clinical trial including patients with Crohn's disease located in the terminal
      ileum that require infliximab treatment following recent consensus statements on
      inflammatory bowel disease treatment: moderate to severe disease activity in
      patients that fail to respond to steroid therapy or immunomodulatory therapy.
      Patients will be randomized to receive either infliximab or undergo a
      laparoscopic ileocolic resection. Primary outcomes are quality of life and costs.
      Secondary outcomes are hospital stay, early and late morbidity, sick leave and
      surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory
      Bowel Disease Questionnaire at a 5% two sided significance level with a power of
      80%, a sample size of 65 patients per treatment group can be calculated. An
      economic evaluation will be performed by assessing the marginal direct medical,
      non-medical and time costs and the costs per Quality Adjusted Life Year (QALY)
      will be calculated. For both treatment strategies a cost-utility ratio will be
      calculated. Patients will be included from December 2007. DISCUSSION: The LIR!C
      trial is a randomized multicenter trial that will provide evidence whether
      infliximab treatment or surgery is the best treatment for recurrent distal
      ileitis in Crohn's disease. TRIAL REGISTRATION: Nederlands Trial Register
      NTR1150.

PMID- 18721466
TI  - Interaction between polymorphisms of the human leukocyte antigen and HPV-16
      variants on the risk of invasive cervical cancer.
AB  - BACKGROUND: Persistent infection with oncogenic types of human papillomavirus
      (HPV) is the major risk factor for invasive cervical cancer (ICC), and non
      European variants of HPV-16 are associated with an increased risk of persistence
      and ICC. HLA class II polymorphisms are also associated with genetic
      susceptibility to ICC. Our aim is to verify if these associations are influenced
      by HPV-16 variability. METHODS: We characterized HPV-16 variants by PCR in 107
      ICC cases, which were typed for HLA-DQA1, DRB1 and DQB1 genes and compared to 257
      controls. We measured the magnitude of associations by logistic regression
      analysis. RESULTS: European (E), Asian-American (AA) and African (Af) variants
      were identified. Here we show that inverse association between DQB1*05 (adjusted
      odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.39-1.12]) and HPV-16
      positive ICC in our previous report was mostly attributable to AA variant
      carriers (OR = 0.27; 95%CI: 0.10-0.75). We observed similar proportions of HLA
      DRB1*1302 carriers in E-P positive cases and controls, but interestingly, this
      allele was not found in AA cases (p = 0.03, Fisher exact test). A positive
      association with DRB1*15 was observed in both groups of women harboring either E
      (OR = 2.99; 95% CI: 1.13-7.86) or AA variants (OR = 2.34; 95% CI: 1.00-5.46).
      There was an inverse association between DRB1*04 and ICC among women with HPV-16
      carrying the 350T [83L] single nucleotide polymorphism in the E6 gene (OR = 0.27;
      95% CI: 0.08-0.96). An inverse association between DQB1*05 and cases carrying
      350G (83V) variants was also found (OR = 0.37; 95% CI: 0.15-0.89). CONCLUSION:
      Our results suggest that the association between HLA polymorphism and risk of ICC
      might be influenced by the distribution of HPV-16 variants.

PMID- 18721468
TI  - Gene Vector Analysis (Geneva): a unified method to detect differentially
      regulated gene sets and similar microarray experiments.
AB  - BACKGROUND: Microarray experiments measure changes in the expression of thousands
      of genes. The resulting lists of genes with changes in expression are then
      searched for biologically related sets using several divergent methods such as
      the Fisher Exact Test (as used in multiple GO enrichment tools), Parametric
      Analysis of Gene Expression (PAGE), Gene Set Enrichment Analysis (GSEA), and the
      connectivity map. RESULTS: We describe an analytical method (Geneva: Gene Vector
      Analysis) to relate genes to biological properties and to other similar
      experiments in a uniform way. This new method works on both gene sets and on gene
      lists/vectors as input queries, and can effectively query databases consisting of
      sets of biologically related sets, or of results from other microarray
      experiments. We also present an improvement to the null model estimate by using
      the empirical background distribution drawn from previous experiments. We
      validated Geneva by rediscovering a number of previous findings, and by finding
      significant relationships within microarrays in the GEO repository. CONCLUSION:
      Provided a reasonable corpus of previous experiments is available, this method is
      more accurate than the class label permutation model, especially for data sets
      with limited number of replicates. Geneva is, moreover, computationally faster
      because the background distributions can be precomputed. We also provide a
      standard evaluation data set based on 5 pairs of related experiments that should
      share similar functional relationships and 28 pairs of unrelated experiments from
      GEO. Discovering relationships amongst GEO data sets has implications for drug
      repositioning, and understanding relationships between diseases and drugs.

PMID- 18721469
TI  - Three-dimensional visualization of cultural clusters in the 1878 yellow fever
      epidemic of New Orleans.
AB  - BACKGROUND: An epidemic may exhibit different spatial patterns with a change in
      geographic scale, with each scale having different conduits and impediments to
      disease spread. Mapping disease at each of these scales often reveals different
      cluster patterns. This paper will consider this change of geographic scale in an
      analysis of yellow fever deaths for New Orleans in 1878. Global clustering for
      the whole city, will be followed by a focus on the French Quarter, then clusters
      of that area, and finally street-level patterns of a single cluster. The three
      dimensional visualization capabilities of a GIS will be used as part of a cluster
      creation process that incorporates physical buildings in calculating mortality-to
      mortality distance. Including nativity of the deceased will also capture cultural
      connection. RESULTS: Twenty-two yellow fever clusters were identified for the
      French Quarter. These generally mirror the results of other global cluster and
      density surfaces created for the entire epidemic in New Orleans. However, the
      addition of building-distance, and disease specific time frame between deaths
      reveal that disease spread contains a cultural component. Same nativity mortality
      clusters emerge in a similar time frame irrespective of proximity. Italian
      nativity mortalities were far more densely grouped than any of the other cohorts.
      A final examination of mortalities for one of the nativity clusters reveals that
      further sub-division is present, and that this pattern would only be revealed at
      this scale (street level) of investigation. CONCLUSION: Disease spread in an
      epidemic is complex resulting from a combination of geographic distance,
      geographic distance with specific connection to the built environment, disease
      specific time frame between deaths, impediments such as herd immunity, and social
      or cultural connection. This research has shown that the importance of cultural
      connection may be more important than simple proximity, which in turn might mean
      traditional quarantine measures should be re-evaluated.

PMID- 18721470
TI  - The transcriptional cofactor MIER1-beta negatively regulates histone
      acetyltransferase activity of the CREB-binding protein.
AB  - BACKGROUND: Mier1 encodes a novel transcriptional regulator and was originally
      isolated as a fibroblast growth factor early response gene. Two major protein
      isoforms have been identified, MIER1alpha and beta, which differ in their C
      terminal sequence. Previously, we demonstrated that both isoforms recruit histone
      deacetylase 1 (HDAC1) to repress transcription. To further explore the role of
      MIER1 in chromatin remodeling, we investigated the functional interaction of
      MIER1 with the histone acetyltransferase (HAT), Creb-binding protein (CBP).
      FINDINGS: Using GST pull-down assays, we demonstrate that MIER1 interacts with
      CBP and that this interaction involves the N-terminal half (amino acids 1-283) of
      MIER1, which includes the acidic activation and ELM2 domains and the C-terminal
      half (amino acids 1094-2441) of CBP, which includes the bromo-, HAT, C/H3 and
      glutamine-rich domains. Functional analysis, using HEK293 cells, shows that the
      CBP bound to MIER1 in vivo has no detectable HAT activity. Histone 4 peptide
      binding assays demonstrate that this inhibition of HAT activity is not the result
      of interference with histone binding. CONCLUSION: Our data indicate that an
      additional mechanism by which MIER1 could repress transcription involves the
      inhibition of histone acetyltransferase activity.

PMID- 18721471
TI  - Survey of extrachromosomal circular DNA derived from plant satellite repeats.
AB  - BACKGROUND: Satellite repeats represent one of the most dynamic components of
      higher plant genomes, undergoing rapid evolutionary changes of their nucleotide
      sequences and abundance in a genome. However, the exact molecular mechanisms
      driving these changes and their eventual regulation are mostly unknown. It has
      been proposed that amplification and homogenization of satellite DNA could be
      facilitated by extrachromosomal circular DNA (eccDNA) molecules originated by
      recombination-based excision from satellite repeat arrays. While the models
      including eccDNA are attractive for their potential to explain rapid turnover of
      satellite DNA, the existence of satellite repeat-derived eccDNA has not yet been
      systematically studied in a wider range of plant genomes. RESULTS: We performed a
      survey of eccDNA corresponding to nine different families and three subfamilies
      of satellite repeats in ten species from various genera of higher plants
      (Arabidopsis, Oryza, Pisum, Secale, Triticum and Vicia). The repeats selected for
      this study differed in their monomer length, abundance, and chromosomal
      localization in individual species. Using two-dimensional agarose gel
      electrophoresis followed by Southern blotting, eccDNA molecules corresponding to
      all examined satellites were detected. EccDNA occurred in the form of nicked
      circles ranging from hundreds to over eight thousand nucleotides in size. Within
      this range the circular molecules occurred preferentially in discrete size
      intervals corresponding to multiples of monomer or higher-order repeat lengths.
      CONCLUSION: This work demonstrated that satellite repeat-derived eccDNA is common
      in plant genomes and thus it can be seriously considered as a potential
      intermediate in processes driving satellite repeat evolution. The observed size
      distribution of circular molecules suggests that they are most likely generated
      by molecular mechanisms based on homologous recombination requiring long
      stretches of sequence similarity.

PMID- 18721472
TI  - Protein structure search and local structure characterization.
AB  - BACKGROUND: Structural similarities among proteins can provide valuable insight
      into their functional mechanisms and relationships. As the number of available
      three-dimensional (3D) protein structures increases, a greater variety of studies
      can be conducted with increasing efficiency, among which is the design of protein
      structural alphabets. Structural alphabets allow us to characterize local
      structures of proteins and describe the global folding structure of a protein
      using a one-dimensional (1D) sequence. Thus, 1D sequences can be used to identify
      structural similarities among proteins using standard sequence alignment tools
      such as BLAST or FASTA. RESULTS: We used self-organizing maps in combination with
      a minimum spanning tree algorithm to determine the optimum size of a structural
      alphabet and applied the k-means algorithm to group protein fragnts into
      clusters. The centroids of these clusters defined the structural alphabet. We
      also developed a flexible matrix training system to build a substitution matrix
      (TRISUM-169) for our alphabet. Based on FASTA and using TRISUM-169 as the
      substitution matrix, we developed the SA-FAST alignment tool. We compared the
      performance of SA-FAST with that of various search tools in database-scale search
      tasks and found that SA-FAST was highly competitive in all tests conducted.
      Further, we evaluated the performance of our structural alphabet in recognizing
      specific structural domains of EGF and EGF-like proteins. Our method successfully
      recovered more EGF sub-domains using our structural alphabet than when using
      other structural alphabets. SA-FAST can be found at
      http://140.113.166.178/safast/. CONCLUSION: The goal of this project was two
      fold. First, we wanted to introduce a modular design pipeline to those who have
      been working with structural alphabets. Secondly, we wanted to open the door to
      researchers who have done substantial work in biological sequences but have yet
      to enter the field of protein structure research. Our experiments showed that by
      transforming the structural representations from 3D to 1D, several 1D-based tools
      can be applied to structural analysis, including similarity searches and
      structural motif finding.

PMID- 18721473
TI  - Integration of relational and hierarchical network information for protein
      function prediction.
AB  - BACKGROUND: In the current climate of high-throughput computational biology, the
      inference of a protein's function from related measurements, such as protein
      protein interaction relations, has become a canonical task. Most existing
      technologies pursue this task as a classification problem, on a term-by-term
      basis, for each term in a database, such as the Gene Ontology (GO) database, a
      popular rigorous vocabulary for biological functions. However, ontology
      structures are essentially hierarchies, with certain top to bottom annotation
      rules which protein function predictions should in principle follow. Currently,
      the most common approach to imposing these hierarchical constraints on network
      based classifiers is through the use of transitive closure to predictions.
      RESULTS: We propose a probabilistic framework to integrate information in
      relational data, in the form of a protein-protein interaction network, and a
      hierarchically structured database of terms, in the form of the GO database, for
      the purpose of protein function prediction. At the heart of our framework is a
      factorization of local neighborhood information in the protein-protein
      interaction network across successive ancestral terms in the GO hierarchy. We
      introduce a classifier within this framework, with computationally efficient
      implementation, that produces GO-term predictions that naturally obey a
      hierarchical 'true-path' consistency from root to leaves, without the need for
      further post-processing. CONCLUSION: A cross-validation study, using data from
      the yeast Saccharomyces cerevisiae, shows our method offers substantial
      improvements over both standard 'guilt-by-association' (i.e., Nearest-Neighbor)
      and more refined Markov random field methods, whether in their original form or
      when post-processed to artificially impose 'true-path' consistency. Further
      analysis of the results indicates that these improvements are associated with
      increased predictive capabilities (i.e., increased positive predictive value),
      and that this increase is consistent uniformly with GO-term depth. Additional in
      silico validation on a collection of new annotations recently added to GO
      confirms the advantages suggested by the cross-validation study. Taken as a
      whole, our results show that a hierarchical approach to network-based protein
      function prediction, that exploits the ontological structure of protein
      annotation databases in a principled manner, can offer substantial advantages
      over the successive application of 'flat' network-based methods.

PMID- 18721474
TI  - Stigma, social reciprocity and exclusion of HIV/AIDS patients with illicit drug
      histories: a study of Thai nurses' attitudes.
AB  - BACKGROUND: Stigma is a key barrier for the delivery of care to patients living
      with HIV/AIDS (PLWHA). In the Asia region, the HIV/AIDS epidemic has
      disproportionately affected socially marginalised groups, in particular,
      injecting drug users. The effect of the stigmatising attitudes towards injecting
      drug users on perceptions of PLWHA within the health care contexts has not been
      thoroughly explored, and typically neglected in terms of stigma intervention.
      METHODS: Semi-structured interviews were conducted with a group of twenty Thai
      trainee and qualified nurses. Drawing upon the idea of 'social reciprocity', this
      paper examines the constructions of injecting drug users and PLWHA by a group of
      Thai nurses. Narratives were explored with a focus on how participants' views
      concerning the high-risk behaviour of injecting drug use might influence their
      attitudes towards PLWHA. RESULTS: The analysis shows that active efforts were
      made by participants to separate their views of patients living with HIV/AIDS
      from injecting drug users. While the former were depicted as patients worthy of
      social support and inclusion, the latter were excluded on the basis that they
      were perceived as irresponsible 'social cheaters' who pose severe social and
      economic harm to the community. Absent in the narratives were references to wider
      socio-political and epidemiological factors related to drug use and needle
      sharing that expose injecting drug users to risk; these behaviours were
      constructed as individual choices, allowing HIV positive drug users to be blamed
      for their seropositive status. These attitudes could potentially have indirect
      negative implications on the nurses' opinions of patients living with HIV/AIDS
      more generally. CONCLUSION: Decreasing the stigma associated with illicit drugs
      might play crucial role in improving attitudes towards patients living with
      HIV/AIDS. Providing health workers with a broader understanding of risk
      behaviours and redirecting government injecting drug policy to harm reduction are
      discussed as some of the ways for stigma intervention to move forward.

PMID- 18721475
TI  - Late diagnosed necrotizing fasciitis as a cause of multiorgan dysfunction
      syndrome: A case report.
AB  - Necrotizing fasciitis is a rapidly progressive, life-threatening soft tissue
      bacterial infection. We present a serious case of a 43-year-old male who suffered
      from necrotizing fasciitis of the left leg in whom a delayed diagnosis caused
      multiorgan dysfunction.Early recognition of important symptoms is essential in
      the management and surgical debridement of necrotizing fasciitis. Treatment
      should include comprehensive supportive measures (early goal-directed therapy,
      adequate ventilation strategy, activated protein C dosage, tight glucose control,
      steroids, renal replacement therapy) and early antibiotic therapy based on
      microbiologic monitoring. The pathophysiology and etiologic factors of
      necrotizing fasciitis are discussed.

PMID- 18721476
TI  - Results of emergency Hartmann's operation for obstructive or perforated left
      sided colorectal cancer.
AB  - BACKGROUND: Up to 15% of colorectal cancer (CRC) patients present with
      obstructive or perforated tumours, and require emergency surgery. The Hartmann's
      procedure (HP) provides the opportunity to achieve a potentially curative (R0)
      resection, while minimizing surgical trauma in poor-risk patients. The aim of
      this study was to assess the surgical (operative mortality), and oncological
      (long-term survival after curative resection) results of emergency HP for
      obstructive or perforated left-sided CRC. METHODS: A retrospective review of 50
      patients who underwent emergency HP for perforated/obstructive CRC in our
      institution between 1995 and 2006. RESULTS: Median age of patients was 75 (range
      22-95) years and the indications for HP were obstruction (32) and perforation (18
      patients). Operative mortality and morbidity were 8% and 26% respectively. 35
      patients (70%) were operated with a curative intent; in this group, overall 1-, 3
      and 5-year survival rates were 80%, 54% and 40%. In univariate analysis, the
      presence of lymph node metastases was associated with poor 5-year survival (62%
      [Stage II] vs. 27% [Stage III], log-rank test, p = 0.02). Eleven patients (22%)
      had their operation reversed with a median delay of 225 (range 94-390) days. In
      this subgroup, two patients died from distant metastases, but there were no
      instances of loco-regional recurrence. CONCLUSION: Hartmann's operation remains a
      good option to palliate symptoms in 30% of patients with left-sided CRC who are
      not candidates to a curative resection. For those who have a curative resection,
      the oncological outcome is acceptable, especially stage II patients, who appear
      to benefit the most from this surgical strategy.

PMID- 18721477
TI  - Molecular evolution of the keratin associated protein gene family in mammals,
      role in the evolution of mammalian hair.
AB  - BACKGROUND: Hair is unique to mammals. Keratin associated proteins (KRTAPs),
      which contain two major groups: high/ultrahigh cysteine and high glycine
      tyrosine, are one of the major components of hair and play essential roles in the
      formation of rigid and resistant hair shafts. RESULTS: The KRTAP family was
      identified as being unique to mammals, and near-complete KRTAP gene repertoires
      for eight mammalian genomes were characterized in this study. An expanded KRTAP
      gene repertoire was found in rodents. Surprisingly, humans have a similar number
      of genes as other primates despite the relative hairlessness of humans. We
      identified several new subfamilies not previously reported in the high/ultrahigh
      cysteine KRTAP genes. Genes in many subfamilies of the high/ultrahigh cysteine
      KRTAP genes have evolved by concerted evolution with frequent gene conversion
      events, yielding a higher GC base content for these gene sequences. In contrast,
      the high glycine-tyrosine KRTAP genes have evolved more dynamically, with fewer
      gene conversion events and thus have a lower GC base content, possibly due to
      positive selection. CONCLUSION: Most of the subfamilies emerged early in the
      evolution of mammals, thus we propose that the mammalian ancestor should have a
      diverse KRTAP gene repertoire. We propose that hair content characteristics have
      evolved and diverged rapidly among mammals because of rapid divergent evolution
      of KRTAPs between species. In contrast, subfamilies of KRTAP genes have been
      homogenized within each species due to concerted evolution.

PMID- 18721478
TI  - Ocular accommodation and cognitive demand: an additional indicator besides pupil
      size and cardiovascular measures?
AB  - BACKGROUND: The aim of the present study was to assess accommodation as a
      possible indicator of changes in the autonomic balance caused by altered
      cognitive demand. Accounting for accommodative responses from a human factors
      perspective may be motivated by the interest of designing virtual image displays
      or by establishing an autonomic indicator that allows for remote measurement at
      the human eye. Heart period, pulse transit time, and the pupillary response were
      considered as reference for possible closed-loop accommodative effects. Cognitive
      demand was varied by presenting monocularly numbers at a viewing distance of 5 D
      (20 cm) which had to be read, added or multiplied; further, letters were
      presented in a "n-back" task. RESULTS: Cardiovascular parameters and pupil size
      indicated a change in autonomic balance, while error rates and reaction time
      confirmed the increased cognitive demand during task processing. An observed
      decrease in accommodation could not be attributed to the cognitive demand itself
      for two reasons: (1) the cognitive demand induced a shift in gaze direction
      which, for methodological reasons, accounted for a substantial part of the
      observed accommodative changes. (2) Remaining effects disappeared when the
      correctness of task processing was taken into account. CONCLUSION: Although the
      expectation of accommodation as possible autonomic indicator of cognitive demand
      was not confirmed, the present results are informative for the field of applied
      psychophysiology noting that it seems not to be worthwhile to include closed-loop
      accommodation in future studies. From a human factors perspective, expected
      changes of accommodation due to cognitive demand are of minor importance for
      design specifications - of, for example, complex visual displays.

PMID- 18721479
TI  - The Hordaland Women's Cohort: a prospective cohort study of incontinence, other
      urinary tract symptoms and related health issues in middle-aged women.
AB  - BACKGROUND: Urinary incontinence (UI) is a prevalent symptom in middle-aged
      women, but data on incidence is limited and rarely reported. In order to analyze
      incidence, remission, or development patterns of severity and types of UI, we
      have established a 15-year prospective cohort (1997-2012). METHODS: The Cohort is
      based on the national collection of health data gathered from county studies
      (CONOR). Hordaland Health Study (HUSK) is one of them from Hordaland County. Each
      of the county studies may have local sub-studies and our Cohort is one of them.
      The Cohort included women aged 40-45 in order to have a broad approach to women's
      health including UI and other lower urinary tract symptoms (LUTS). A one fifth
      random sampling from HUSK was used to create the Cohort in 1997-1999. For the
      necessary sample size a preliminary power calculation, based on a 70% response
      rate at inclusion and 5% annual attrition rates was used. The Cohort is planned
      to collect data through questionnaires every second year for the 15-year period
      from 1997-2012. DISCUSSION: The Cohort represents a relatively large random
      sample (N = 2,230) of about 15% of the total population of women born between
      1953-57 in the county of Hordaland. Our data shows that the cohort population is
      very similar to the source population. The baseline demographic, social and
      medical characteristics of the Cohort are compared with the rest of women in HUSK
      (N = 7,746) and there were no significant differences between them except for the
      level of education (P = 0.001) and yearly income (P = 0.018), which were higher
      in the Cohort population. Urological characteristics of participants from the
      Cohort (N = 1,920) were also compared with the other participants (N = 3,400).
      There were no significant statistical differences except for somewhat more
      urinary continence (P = 0.04), more stress incontinence (P = 0.048) and smaller
      amount of leakage (P = 0.015) in the Cohort. In conclusion, the Cohort is
      population-based, with little selection bias, and thus is a rather unique study
      for investigating UI and LUTS in comparison with many other projects with similar
      purposes.

PMID- 18721480
TI  - Missed injuries in trauma patients: A literature review.
AB  - BACKGROUND: Overlooked injuries and delayed diagnoses are still common problems
      in the treatment of polytrauma patients. Therefore, ongoing documentation
      describing the incidence rates of missed injuries, clinically significant missed
      injuries, contributing factors and outcome is necessary to improve the quality of
      trauma care. This review summarizes the available literature on missed injuries,
      focusing on overlooked muscoloskeletal injuries. METHODS: Manuscripts dealing
      with missed injuries after trauma were reviewed. The following search modules
      were selected in PubMed: Missed injuries, Delayed diagnoses, Trauma,
      Musculoskeletal injuires. Three time periods were differentiated: (n = 2, 1980
      1990), (n = 6, 1990-2000), and (n = 9, 2000-Present). RESULTS: We found a wide
      spread distribution of missed injuries and delayed diagnoses incidence rates
      (1.3% to 39%). Approximately 15 to 22.3% of patients with missed injuries had
      clinically significant missed injuries. Furthermore, we observed a decrease of
      missed pelvic and hip injuries within the last decade. CONCLUSION: The lack of
      standardized studies using comparable definitions for missed injuries and
      clinically significant missed injuries call for further investigations, which are
      necessary to produce more reliable data. Furthermore, improvements in diagnostic
      techniques (e.g. the use of multi-slice CT) may lead to a decreased incidence of
      missed pelvic injuries. Finally, the standardized tertiary trauma survey is
      vitally important in the detection of clinically significant missed injuries and
      should be included in trauma care.

PMID- 18721482
TI  - Regional differences in mortality in Greece (1984-2004): the case of Thrace.
AB  - BACKGROUND: Mortality differences at national level can generate hypothesis on
      possible causal association that could be further investigated. The aim of the
      present study was to identify regions with high mortality rates in Greece.
      METHODS: Age adjusted specific mortality rates by gender were calculated in each
      of the 10 regions of Greece during the period 1984-2004. Moreover standardized
      mortality rates (SMR) were also calculated by using population census data of
      years 1981, 1991, 2001. The mortality rates were examined in relation to GDP per
      capita, the ratio of hospital beds, and doctors per population for each region.
      RESULTS: During the study period, the region of Thrace recorded the highest
      mortality rate at almost all age groups in both sexes among the ten Greek
      regions. Thrace had one of the lowest GDP per capita (11,123 Euro) and recorded
      low ratios of Physicians (284) per 100,000 inhabitants in comparison to the
      national ratios. Moreover the ratio of hospital beds per population was in Thrace
      very low (268/100,000) in comparison to the national ratio (470/100,000). Thrace
      is the Greek region with the highest percentage of Muslim population (33%).
      Multivariate analysis revealed that GDP and doctors/100000 inhabitants were
      associated with increased mortality in Thrace. CONCLUSION: Thrace is the region
      with the highest mortality rate in Greece. Further research is needed to assess
      the contribution of each possible risk factor to the increased mortality rate of
      Thrace which could have important public health implications.

PMID- 18721483
TI  - An association study of ADSS gene polymorphisms with schizophrenia.
AB  - BACKGROUND: Adenylosuccinate synthase (ADSS) catalyzes the first committed step
      of AMP synthesis. It was suggested that the blood-derived RNA of ADSS was down
      regulated in schizophrenia (SZ) and one of the eight putative biomarker genes to
      discriminate SZ from normal controls. However, it remains unclear whether the
      reduction of ADSS RNA is due to the polymorphisms of the gene or not. METHODS: We
      attempted to examine the association of ADSS gene with schizophrenia in a Chinese
      population of 480 schizophrenics and 502 normal controls. Genotyping was
      performed by the Sequenom platform. RESULTS: The 6 marker SNPs (rs3102460,
      rs3127459, rs3127460, rs3127465, rs3006001, and rs3003211) were genotyped. The
      frequencies of alleles, genotypes, and haplotypes were tested between cases and
      controls. There was no significant difference of genotypic, allelic, or
      haplotypic distributions of the 6 SNPs between the two groups. CONCLUSION: Our
      data did not support ADSS gene as a susceptibility gene for SZ in Chinese Han
      population. Large sample size study is needed to validate or replicate our
      association study, especially from other ethnic populations.

PMID- 18721481
TI  - A comprehensive analysis of the naturally occurring polymorphisms in HIV-1 Vpr:
      potential impact on CTL epitopes.
AB  - The enormous genetic variability reported in HIV-1 has posed problems in the
      treatment of infected individuals. This is evident in the form of HIV-1 resistant
      to antiviral agents, neutralizing antibodies and cytotoxic T lymphocytes (CTLs)
      involving multiple viral gene products. Based on this, it has been suggested that
      a comprehensive analysis of the polymorphisms in HIV proteins is of value for
      understanding the virus transmission and pathogenesis as well as for the efforts
      towards developing anti-viral therapeutics and vaccines. This study, for the
      first time, describes an in-depth analysis of genetic variation in Vpr using
      information from global HIV-1 isolates involving a total of 976 Vpr sequences.
      The polymorphisms at the individual amino acid level were analyzed. The residues
      9, 33, 39, and 47 showed a single variant amino acid compared to other residues.
      There are several amino acids which are highly polymorphic. The residues that
      show ten or more variant amino acids are 15, 16, 28, 36, 37, 48, 55, 58, 59, 77,
      84, 86, 89, and 93. Further, the variant amino acids noted at residues 60, 61,
      34, 71 and 72 are identical. Interestingly, the frequency of the variant amino
      acids was found to be low for most residues. Vpr is known to contain multiple CTL
      epitopes like protease, reverse transcriptase, Env, and Gag proteins of HIV-1.
      Based on this, we have also extended our analysis of the amino acid polymorphisms
      to the experimentally defined and predicted CTL epitopes. The results suggest
      that amino acid polymorphisms may contribute to the immune escape of the virus.
      The available data on naturally occurring polymorphisms will be useful to assess
      their potential effect on the structural and functional constraints of Vpr and
      also on the fitness of HIV-1 for replication.

PMID- 18721484
TI  - Native human autoantibodies targeting GIPC1 identify differential expression in
      malignant tumors of the breast and ovary.
AB  - BACKGROUND: We have been studying the native humoral immune response to cancer
      and have isolated a library of fully human autoantibodies to a variety of
      malignancies. We previously described the isolation and characterization of two
      fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients
      that target the protein known as GIPC1, an accessory PDZ-domain binding protein
      involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7
      and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer
      tissue with no reactivity with normal breast tissue. METHODS: The current study
      employs cELISA, flow cytometry, Western blot analysis as well as
      immunocytochemistry, and immunohistochemistry. Data is analyzed statistically
      with the Fisher one-tail and two-tail tests for two independent samples. RESULTS:
      By screening several other cancer cell lines with 27.F7 and 27.B1 we found
      consistently strong staining of other human cancer cell lines including SKOV-3
      (an ovarian cancer cell line). To further clarify the association of GIPC1 with
      breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using
      immunocytochemical and immunohistochemical techniques. An immunohistochemical
      study of normal ovarian tissue, benign, borderline and malignant ovarian serous
      tumors, and different types of breast cancer revealed high expression of GIPC1
      protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1
      demonstrate differential staining of borderline ovarian tumors. Examination of
      different types of breast cancer demonstrates that the level of GIPC1 expression
      depends on tumor invasiveness and displays a higher expression than in benign
      tumors. CONCLUSION: The present pilot study demonstrates that the GIPC1 protein
      is overexpressed in ovarian and breast cancer, which may provide an important
      diagnostic and prognostic marker and will constitute the basis for further study
      of the role that this protein plays in malignant diseases. In addition, this
      study suggests that human monoclonal antibodies 27.F7 and 27.B1 should be further
      evaluated as potential diagnostic tools.

PMID- 18721485
TI  - SynBlast: assisting the analysis of conserved synteny information.
AB  - MOTIVATION: In the last years more than 20 vertebrate genomes have been
      sequenced, and the rate at which genomic DNA information becomes available is
      rapidly accelerating. Gene duplication and gene loss events inherently limit the
      accuracy of orthology detection based on sequence similarity alone. Fully
      automated methods for orthology annotation do exist but often fail to identify
      individual members in cases of large gene families, or to distinguish missing
      data from traceable gene losses. This situation can be improved in many cases by
      including conserved synteny information. RESULTS: Here we present the SynBlast
      pipeline that is designed to construct and evaluate local synteny information.
      SynBlast uses the genomic region around a focal reference gene to retrieve
      candidates for homologous regions from a collection of target genomes and ranks
      them in accord with the available evidence for homology. The pipeline is intended
      as a tool to aid high quality manual annotation in particular in those cases
      where automatic procedures fail. We demonstrate how SynBlast is applied to
      retrieving orthologous and paralogous clusters using the vertebrate Hox and
      ParaHox clusters as examples. SOFTWARE: The SynBlast package written in Perl is
      available under the GNU General Public License at http://www.bioinf.uni
      leipzig.de/Software/SynBlast/.

PMID- 18721487
TI  - Occurrence of lactational mastitis and medical management: a prospective cohort
      study in Glasgow.
AB  - BACKGROUND: Lactational mastitis is a painful, debilitating condition that if
      inappropriately managed, may lead women to discontinue breastfeeding prematurely.
      The aim of this paper is to report the incidence of mastitis in the first six
      months postpartum in a Scottish population, its impact on breastfeeding duration
      and to describe the type and appropriateness of the support and management
      received by affected women from health professionals. METHODS: A longitudinal
      study of 420 breastfeeding women was undertaken in Glasgow in 2004/05.
      Participants were recruited and completed a baseline questionnaire before
      discharge from hospital. Cases of mastitis were reported either directly to the
      researchers or were detected during regular follow-up telephone interviews at
      weeks 3, 8, 18 and 26. Women experiencing mastitis provided further information
      of their symptoms and the management and advice they received from health
      professionals. RESULTS: In total, 74 women (18%) experienced at least one episode
      of mastitis. More than one half of initial episodes (53%) occurred within the
      first four weeks postpartum. One in ten women (6/57) were inappropriately advised
      to either stop breastfeeding from the affected breast or to discontinue
      breastfeeding altogether. CONCLUSION: Approximately one in six women is likely to
      experience one or more episodes of mastitis whilst breastfeeding. A small but
      clinically important proportion of women continue to receive inappropriate
      management advice from health professionals which, if followed, could lead them
      to unnecessarily deprive their infants prematurely of the known nutritional and
      immunological benefits of breast milk.

PMID- 18721486
TI  - A human monoclonal autoantibody to breast cancer identifies the PDZ domain
      containing protein GIPC1 as a novel breast cancer-associated antigen.
AB  - BACKGROUND: We have been studying the native autoimmune response to cancer
      through the isolation of human monoclonal antibodies that are cancer specific
      from cancer patients. To facilitate this work we previously developed a fusion
      partner cell line for human lymphocytes, MFP-2, that fuses efficiently with both
      human lymph node lymphocytes and peripheral blood lymphocytes. Using this unique
      trioma fusion partner cell line we isolated a panel of autologous human
      monoclonal antibodies, from both peripheral blood and lymph node lymphocytes,
      which are representative of the native repertoire of anti-cancer specific
      antibodies from breast cancer patients. METHODS: The current study employs
      immunocytochemistry, immunohistochemistry, Western blot analysis as well as
      Northern blots, Scatchard binding studies and finally SEREX analysis for target
      antigen identification. RESULTS: By application of an expression cloning
      technique known as SEREX, we determined that the target antigen for two
      monoclonal antibodies, 27.B1 and 27.F7, derived from lymph node B-cells of a
      breast cancer patient, is the PDZ domain-containing protein known as GIPC1. This
      protein is highly expressed not only in cultured human breast cancer cells, but
      also in primary and metastatic tumor tissues and its overexpression appears to be
      cancer cell specific. Confocal microscopy revealed cell membrane and cytoplasmic
      localization of the target protein, which is consistent with previous studies of
      this protein. CONCLUSION: We have determined that GIPC1 is a novel breast cancer
      associated immunogenic antigen that is overexpressed in breast cancer. Its role,
      however, in the initiation and/or progression of breast cancer remains unclear
      and needs further clarification.

PMID- 18721489
TI  - Influence of genotyping error in linkage mapping for complex traits--an analytic
      study.
AB  - BACKGROUND: Despite the current trend towards large epidemiological studies of
      unrelated individuals, linkage studies in families are still thoroughly being
      utilized as tools for disease gene mapping. The use of the single-nucleotide
      polymorphisms (SNP) array technology in genotyping of family data has the
      potential to provide more informative linkage data. Nevertheless, SNP array data
      are not immune to genotyping error which, as has been suggested in the past,
      could dramatically affect the evidence for linkage especially in selective
      designs such as affected sib pair (ASP) designs. The influence of genotyping
      error on selective designs for continuous traits has not been assessed yet.
      RESULTS: We use the identity-by-descent (IBD) regression-based paradigm for
      linkage testing to analytically quantify the effect of simple genotyping error
      models under specific selection schemes for sibling pairs. We show, for example,
      that in extremely concordant (EC) designs, genotyping error leads to decreased
      power whereas it leads to increased type I error in extremely discordant (ED)
      designs. Perhaps surprisingly, the effect of genotyping error on inference is
      most severe in designs where selection is least extreme. We suggest a genomic
      control for genotyping errors via a simple modification of the intercept in the
      regression for linkage. CONCLUSION: This study extends earlier findings:
      genotyping error can substantially affect type I error and power in selective
      designs for continuous traits. Designs involving both EC and ED sib pairs are
      fairly immune to genotyping error. When those designs are not feasible the simple
      genomic control strategy that we suggest offers the potential to deliver more
      robust inference, especially if genotyping is carried out by SNP array
      technology.

PMID- 18721488
TI  - Mutant polycystin-2 induces proliferation in primary rat tubular epithelial cells
      in a STAT-1/p21-independent fashion accompanied instead by alterations in
      expression of p57KIP2 and Cdk2.
AB  - BACKGROUND: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized
      by the formation of multiple fluid-filled cysts that destroy the kidney
      architecture resulting in end-stage renal failure. Mutations in genes PKD1 and
      PKD2 account for nearly all cases of ADPKD. Increased cell proliferation is one
      of the key features of the disease. Several studies indicated that polycystin-1
      regulates cellular proliferation through various signaling pathways, but little
      is known about the role played by polycystin-2, the product of PKD2. Recently, it
      was reported that as with polycystin-1, polycystin-2 can act as a negative
      regulator of cell growth by modulating the levels of the cyclin-dependent kinase
      inhibitor, p21 and the activity of the cyclin-dependent kinase 2, Cdk2. METHODS:
      Here we utilized different kidney cell-lines expressing wild-type and mutant PKD2
      as well as primary tubular epithelial cells isolated from a PKD transgenic rat to
      further explore the contribution of the p21/Cdk2 pathway in ADPKD proliferation.
      RESULTS: Surprisingly, over-expression of wild-type PKD2 in renal cell lines
      failed to inactivate Cdk2 and consequently had no effect on cell proliferation.
      On the other hand, expression of mutated PKD2 augmented proliferation only in the
      primary tubular epithelial cells of a rat model but this was independent of the
      STAT-1/p21 pathway. On the contrary, multiple approaches revealed unequivocally
      that expression of the cyclin-dependent kinase inhibitor, p57KIP2, is
      downregulated, while p21 remains unchanged. This p57 reduction is accompanied by
      an increase in Cdk2 levels. CONCLUSION: Our results indicate the probable
      involvement of p57KIP2 on epithelial cell proliferation in ADPKD implicating a
      new mechanism for mutant polycystin-2 induced proliferation. Most importantly,
      contrary to previous studies, abnormal proliferation in cells expressing mutant
      polycystin-2 appears to be independent of STAT-1/p21.

PMID- 18721490
TI  - Sustained effects in hypercholesterolaemic patients on combined
      simvastatin/ezetimibe treatment: observational cohort study in clinical practice.
AB  - BACKGROUND: In order to reduce individual cardiovascular risk, many patients
      require life-long lipid-lowering therapy, often as a drug combination approach.
      We aimed to describe the usage pattern, effectiveness and tolerability of long
      term treatment with lipid-lowering agents, with particular focus on an oral
      combination of simvastatin (SIM 10, 20, 40 or 80 mg) plus ezetimibe (EZ 10 mg).
      METHODS: A prospective, observational study in 512 general practices throughout
      Germany. From a sample of patients at moderate or high cardiovascular risk who
      had previously taken part in a half-year study of an SIM/EZ combination, 5485
      patients were documented after 1 year of treatment (mean 58 +/- 16 weeks) with
      regard to lipid parameters, adverse drug reactions (ADRs) and adverse events.
      RESULTS: At the start of follow-up, 78.6% of patients were still on the SIM/EZ
      combination. At the end of follow-up, mean low density lipoprotein cholesterol
      (LDL-C) in patients on the combination versus those on other lipid-lowering
      therapy was reduced by 29.3 vs. 17.6% compared with baseline, total cholesterol
      by 23.1 vs. 14.5%, mean high density lipoprotein cholesterol (HDL-C) was
      increased by 15.9 vs. 13.4%, and mean triglycerides were reduced by 16.1 vs.
      7.9%. Individual LDL-C targets were achieved by 56.6% on the SIM/EZ combination
      versus 35.9% on other therapy. In the long term (but not the short term), low
      acceptance of nutrition counselling as rated by the physician was associated with
      poor lipid levels. ADRs during follow-up occurred in 18 patients (0.3%; all cases
      non-serious), with seven cases of myalgia, and three cases each of nausea or
      arthralgia. CONCLUSIONS: This observational study showed that long-term therapy
      with the SIM/EZ combination resulted in sustained beneficial effects on serum
      lipids and was well-tolerated. Compared to patients with therapy discontinuations
      or switches, those remaining on the combination had better outcomes regarding
      lipid status.

PMID- 18721491
TI  - [Identification of the CD40 (CD154) ligand expression on the surface of
      conglomerate platelet-monocyte in children with the metabolic syndrome].
AB  - INTRODUCTION: The increased expression of the transmembrane protein CD40 on
      macrophages, endothelium, smooth muscle cells, platelet-monocyte conglomerate is
      connected with an enlarged risk of the occurrence of diseases of the
      cardiovascular system in the metabolic syndrome. THE AIM OF THE STUDY: was to
      establish whether metabolic syndrome in children can already be a precursor of
      cardiovascular diseases. MATERIAL AND METHODS: The study was carried out on 35
      children aged 10-18 years with the metabolic syndrome recognized according to the
      National Cholesterol Educational Program Adult Treatment Panel III (ATP III)
      criteria. The control group consisted of 26 healthy children without risk
      factors. In the examined children we evaluated BMI, the blood pressure, lipids,
      hsCRP, and the HOMA index. The analysis of the expression CD 40L (CD154) was
      performed with a three-color flow cytometer. The identification surrendered 104
      cells. Statistical analysis was performed with use of U-Mann-Whitney test, for
      correlation analysis we used Spearman and Pearson tests. RESULTS: We observed an
      elevated expression of CD40 ligand on the surface on platelet-monocyte
      conglomerate in patients with the metabolic syndrome compared to healthy children
      (12.7 vs. 4.95%, p=0.0036). In addition, we found a statistically significant
      correlation between the expression of the CD40L and HOMA index (r = -0.33,
      p<0.028). CONCLUSIONS: Enlarged expression of the transmembrane protein CD40L not
      only initiates and influences the progression of the atherosclerosis, but
      modulates the architecture of atherosclerotic plaque as well.

PMID- 18721492
TI  - [Evaluation of adiponectin level in children and adolescents with diabetes type
      1].
AB  - INTRODUCTION: Adipose tissue is not only an energy storage place, but it also
      secretes numerous "adipocytokines" - substances that have systemic influence.
      Adiponectin has an anti-inflammatory, antiatherogenic properties and increases
      insulin sensitivity. It is emphasized that adiponectin levels are different in
      type 1 and type 2 diabetes. THE AIM OF THE STUDY: was to evaluate adiponectin
      levels in young patients with diabetes type 1, and to analyse of the correlation
      between adiponectin and: BMI, lipid parameters, glomerular filtration rate and
      microalbuminuria. MATERIAL AND METHODS: The study group was formed by 95 patients
      from the Outpatient Diabetology Department 2nd Department of Children's Diseases,
      45 girls and 50 boys, aged from 7 to 20 years (mean - 14.97 yrs) suffering from
      diabetes from 1 to 17 years (mean 6.68 yrs). Control group consisted of healthy
      children, age matched, without family history of cardiovascular diseases. In all
      patients anthropometric measurements were performed (BMI was calculated),
      metabolic control was evaluated on the basis of HbA1c level, microalbuminuria was
      studied in 24 hour urine sample. We assessed glomerular filtration rate
      (endogenous creatinine clearance), lipid parameters and adiponectin level.
      RESULTS: In children and adolescents with diabetes type 1 we found significantly
      higher levels of adiponectin compared to control group: 32.72+/-13.49 vs. 26.53+/
      7.63 ug/ml; p=0.024. Adiponectin level was higher in girls than in boys (33.56
      vs. 28.75 ug/ml; p=0.036). Adiponectin level did not depend on metabolic control
      and on diabetes duration. We found a statistically significant negative
      correlation between adiponectin and creatinine (r=-0.26; p=0.011). In patients
      with diabetic complications we found insignificantly lower adiponectin level
      compared to patients without complications (30.99+/-14.29 vs. 33.67+/-11.68
      ug/ml; p=0.35). CONCLUSIONS: 1. In patients with diabetes type 1 significantly
      higher level of adiponectin was found compared to healthy control group. 2.
      Adiponectin level correlated negatively with creatinine level end
      microalbuminuria. 3. Elevated level of adiponectin in patients without diabetic
      complications may help to explain the pathogenesis of diabetic angiopathy.

PMID- 18721493
TI  - [Trends in age and height at diagnosis of childhood growth hormone deficiency
      during the period 1995-2004].
AB  - THE AIM OF THE STUDY: was to evaluate age and height at the diagnosis of
      childhood growth hormone deficiency in the group of children who were qualified
      to growth hormone (GH) treatment in pediatric endocrinology department at Medical
      University of Gdansk in period 1994-2004. MATERIAL AND METHODS: The analysis
      comprised 170 GH-deficient children (111 boys) in whom GH treatment was indicated
      in our department in the period 1995-2004 yr. RESULTS: At diagnosis the mean age
      was 11,1+/-3,2 yr., mean height -3,6+/-1,0 SDS. Mean age in males was
      significantly higher, than in females, but there was no statistically significant
      difference between them. 25% of patients were pubertal. 44% of children lived in
      rural area, 56% in urban area and the age of diagnosis was similar in both
      groups. Children from rural area were, however, significantly shorter than those
      from urban area. 25.3% of patients started with GH treatment in the period 1995
      2000 yr. and 74.7% after year 2000. Children who started with GH treatment before
      year 2000 were younger (9,6+/-3,6 yr.) than those after year 2000 (11.6+/-2.9
      yr.). They were also significantly shorter (-4.2+/-1.1 SDS) than patients
      diagnosed after year 2000 (-3.4+/-0.9 SDS). Height in 67% of patients diagnosed
      before year 2000 and 36% diagnosed after year 2000 was below -3.5 SDS.
      CONCLUSIONS: Children with GH deficiency were referred to our department
      relatively late and the age of the diagnosis did not decrease during the period
      1995-2004. The deep height deficiency observed in children at the diagnosis of GH
      deficiency decreased after year 2000 but it is still a problem in patients from
      rural area. General practitioners should earlier identify children with height
      deficiency and refer them to pediatric endocrinologists.

PMID- 18721494
TI  - [Ovarian dysfunction after anticancer treatment - possibilities of diagnosis and
      fertility preservation].
AB  - Due to composed anticancer treatment more than 70% of children and adolescents
      are cured. The long-term side effects deteriorating quality of life have a great
      importance. The influence of chemo- and radiotherapy on ovary function, the
      causes of premature menopause, actual possibilities of diagnosis and fertility
      preservation are presented.

PMID- 18721495
TI  - [Testicular function in young men treated in prepubertal period for childhood
      malignancy].
AB  - INTRODUCTION: A complex anticancer treatment leads to different late effects e.g.
      gonadal damage in adulthood. The information about gonadal function (steroido-
      and spermatogenesis) after the treatment in prepubertal period are ambiguous. THE
      AIM OF STUDY: was to evaluate testicular function in young men (Tanner puberty
      stages IV and V) treated in prepubertal period for childhood malignancies.
      MATERIAL AND METHODS: In thirty-two pubertal and postpubertal male survivors of
      childhood cancer (acute lymphoblastic leukemia, ALL - 14, non-Hodgkin lymphoma,
      NHL - 6, Hodgkin lymphoma, HL and solid tumors - 4) testicular volume and serum
      FSH, LH, testosterone, inhibin B and calculated quotient inhibin B:FSH were
      measured. Controls were 15 healthy boys matched by age and Tanner stage. RESULTS:
      In the whole studied group the mean values of FSH, LH and testosterone did not
      differ from control, while inhibin B was lower (87.5+/-96.3 vs. 196.5+/-66.8
      ng/l; p<0,0003). The lowest values of inhibin B were found in HL (46,15+/-35,12
      ng/l) and after ALL treatment (71,1+/-39,8 ng/l). We did not observe differences
      in hormonal parameters after NHL treatment. The inhibin B-to-FSH ratio was lower,
      especially after treatment for HL. CONCLUSIONS: Inhibin B is a sensitive marker
      of gonadal damage. Anticancer therapy in prepubertal period may lead to
      disturbances in spermatogenesis.

PMID- 18721496
TI  - [Anti-mullerian hormone in young women after chemotherapy and infradiaphragmatic
      radiotherapy for childhood cancer].
AB  - INTRODUCTION: Composed anticancer treatment leads to different late effects, such
      as ovarian failure, causing infertility or premature menopause. AIM OF THE STUDY:
      was to analyse ovarian function, particularly anti-mullerian hormone levels, in
      young females after anticancer treatment. PATIENTS AND METHODS: We analysed FSH,
      LH, estradiol and anti-mullerian hormone (AMH) levels on days 3-5 of a menstrual
      cycle in thirty three cancer survivors in mean age 19.1+/-4.7 years treated in
      age 12.0+/-5.6 years for Hodgkin Lymphoma (HL) (n=16), nephroblastoma (n=7), soft
      tissue sarcoma (n=4), germinal tumor (n=3), neuroblastoma (n=2), histiocytosis
      (n=1). Infradiaphragmatic radiotherapy was needed in 16 patients (10 treated for
      HL). Results were compared with healthy girls of the same age. RESULTS: The mean
      values of FSH, LH, E2 and AMH did not differ in all survivors comparing to
      controls. Patients treated for HL with chemo- and radiotherapy presented higher
      FSH levels than controls (8.53+/-3.25 vs. 5.8+/-2.03 mIU/ml; p=0.045). Mean AMH
      levels were lower in all patients that received radiotherapy for the
      infradiaphragmatic region (17.19+/-14.84 pmol/l) than in controls (29.40+/-13.2
      pmol/l; p=0.037). Particular analysis of all cases showed higher (>2 SD) FSH
      levels in 8 patients: 5 patients treated for HL with radiotherapy and higher
      total doses of procarbazine, nitrogen mustard and vinblastine; 2 patients treated
      for soft tissue sarcoma and one patient for Wilms tumor (all received
      radiotherapy). Lowered AMH levels were found in 8 patients treated with chemo-
      and radiotherapy (4 - for HL, 2 - for Wilms tumor and 2 - for soft tissue
      sarcoma). CONCLUSION: Composed anticancer treatment, especially radiotherapy,
      leads to ovarian failure. Decreased AMH values at young adulthood suggest a lower
      ovarian reserve. All causes and first symptoms of ovary damage should be known to
      the doctors who take care of the patients after anticancer treatment.

PMID- 18721497
TI  - [Principle rules in establishing recommendations. Comparison of contemporary
      diabetes recommendations].
AB  - Creation of systematic guidelines for clinical use in diabetes emerges from the
      necessity of treatment quality improvement. Recommendations are validated
      according to current clinical data. Strength of recommendations is established
      based on systematic review of studies, each of which is of certain category due
      to its methodology. There exists an organization called Grades of Recommendation,
      Assessment, Development and Evaluation, the aim of which is to create homogenous
      quality assessment system and category of recommendations. It will be
      accomplished through the evaluation of data quality, creation of recommendations
      and defining its strength. The recommendations of NICE, ADA and PTD (Polish
      Diabetes Association) are very similar with regard to the significance of
      education of patients as well as performing frequent screening for late
      complications of diabetes and autoimmunological diseases. The recommendations are
      different when it comes to target glycemia (fasting blood glycemia, postprandial
      glycemia and HbA1c), especially depending on patient's age. The knowledge on the
      principles of recommendations creation and the symbols of recommendation's
      strength are essential for medical doctors taking care of diabetic patients while
      choosing the treatment method as well as the individualized approach towards
      every patient with diabetes.

PMID- 18721498
TI  - [Neuropathy and type 1 diabetes mellitus].
AB  - Diabetic neuropathy is the most common type of neuropathies. It affects patients
      with both type 1 and type 2 diabetes, but it progresses more rapidly and its
      manifestations are more severe in type 1 diabetes. Although there has been a
      significant progress in the understanding of the clinical aspects of these
      conditions, many questions remain unanswered. Peripheral and autonomic neuropathy
      are strong risk markers for future mortality. Diabetic autonomic neuropathy is a
      serious and common complication of diabetes. DAN frequently coexists with other
      peripheral neuropathies and other diabetic complications, but DAN may be
      isolated, frequently preceding the detection of other complications. The presence
      of the autonomic diabetic neuropathy significantly influences the regulatory
      function of microcirculation, which may predispose to the occurrence of different
      late diabetic complications.

PMID- 18721499
TI  - [Lipoatrophy associated with rapid-acting insulin analogues in young patients
      with type 1 diabetes mellitus].
AB  - Lipoatrophy as a cutaneous complication of insulin therapy has been practically
      forgotten since the introduction of recombinant human insulin. Here we present
      two cases of marked lipoatrophy associated with rapid-acting insulin analogues
      (aspart and lispro) administered with continuous subcutaneous insulin infusion or
      multiple daily injections in a toddler and a young woman with type 1 diabetes
      mellitus. The exact mechanisms related to the development of localized
      lipoatrophy in the insulin injection area are unknown. In cases of lipoatrophy
      the beneficial therapeutic approach is to change the insulin molecule. With
      switching from one insulin analogue to another administered in insulin pump and
      changing the sites of insulin injections no progression of the lipoatrophic
      lesions was observed. Unfortunately, only decrease but no total regression of the
      formed lesions was achieved and future studies are needed to establish the method
      of treatment of localized lipoatrophy in children treated with continuous
      subcutaneous insulin infusion.

PMID- 18721500
TI  - [Clinical similarity and diagnostic difficulties in differentiation of diabetes
      mellitus type 1 and type 2 in adolescence - case report].
AB  - The authors would like to present the difficulties in differentiation of diabetes
      mellitus type 1 and type 2 in adolescence on the basis of two 17 years-old
      patients. In both patients' cases the following symptoms: polydipsia, polyuria
      and weight loss with hyperglycemia and glycosuria have been observed for a few
      months. During laboratory studies some additional abnormalities were observed:
      elevated HbA1c, dyslipidemia and high level of liver enzymes. Normal level of
      insulin as well as C-peptide lack of ketonuria and negative parameters of
      autoimmunologic reaction the supported diagnosis of diabetes mellitus type 2. Due
      to insulin therapy and metformin a correct level of glycemia was achieved.
      CONCLUSION: Decompensated diabetes mellitus type 2 in adolescents may be
      difficult to differentiate with type 1.

PMID- 18721501
TI  - [Severe thrombocytopenia in a child with type 1 diabetes].
AB  - We describe here a young girl who developed severe thrombocytopenia following
      Varicella infection. She was previously diagnosed with diabetes. In addition she
      demonstrated anti-nuclear factor positivity. Immune thrombocytopenic purpura
      induced by varicella is rare in children with diabetes.

PMID- 18721502
TI  - Bartonella species detection in captive, stranded and free-ranging cetaceans.
AB  - We present prevalence of Bartonella spp. for multiple cohorts of wild and captive
      cetaceans. One hundred and six cetaceans including 86 bottlenose dolphins (71
      free-ranging, 14 captive in a facility with a dolphin experiencing debility of
      unknown origin, 1 stranded), 11 striped dolphins, 4 harbor porpoises, 3 Risso's
      dolphins, 1 dwarf sperm whale and 1 pygmy sperm whale (all stranded) were
      sampled. Whole blood (n = 95 live animals) and tissues (n = 15 freshly dead
      animals) were screened by PCR (n = 106 animals), PCR of enrichment cultures (n =
      50 animals), and subcultures (n = 50 animals). Bartonella spp. were detected from
      17 cetaceans, including 12 by direct extraction PCR of blood or tissues, 6 by PCR
      of enrichment cultures, and 4 by subculture isolation. Bartonella spp. were more
      commonly detected from the captive (6/14, 43%) than from free-ranging (2/71,
      2.8%) bottlenose dolphins, and were commonly detected from the stranded animals
      (9/21, 43%; 3/11 striped dolphins, 3/4 harbor porpoises, 2/3 Risso's dolphins,
      1/1 pygmy sperm whale, 0/1 dwarf sperm whale, 0/1 bottlenose dolphin). Sequencing
      identified a Bartonella spp. most similar to B. henselae San Antonio 2 in eight
      cases (4 bottlenose dolphins, 2 striped dolphins, 2 harbor porpoises), B.
      henselae Houston 1 in three cases (2 Risso's dolphins, 1 harbor porpoise), and
      untyped in six cases (4 bottlenose dolphins, 1 striped dolphin, 1 pygmy sperm
      whale). Although disease causation has not been established, Bartonella species
      were detected more commonly from cetaceans that were overtly debilitated or were
      cohabiting in captivity with a debilitated animal than from free-ranging animals.
      The detection of Bartonella spp. from cetaceans may be of pathophysiological
      concern.

PMID- 18721503
TI  - Prognostic implications of normal (<0.10 ng/ml) and borderline (0.10 to 1.49
      ng/ml) troponin elevation levels in critically ill patients without acute
      coronary syndrome.
AB  - Borderline increase of troponin I (cTnI) is associated with higher rates of
      cardiovascular events compared with normal levels in the setting of acute
      coronary syndrome (ACS), but the significance of borderline cTnI levels in
      patients without chest pain may differ. The aim of this study was to determine
      the prognostic implications of intermediate serum cTnI levels in patients without
      ACS in the intensive care unit (ICU). This was a 12-month retrospective study of
      240 patients without ACS in the ICU with normal (<0.1 ng/ml) or intermediate (0.1
      to 1.49 ng/ml) cTnI levels. End points included in-hospital mortality, lengths of
      ICU and hospital stays, and rates of postdischarge readmission and mortality.
      Overall in-hospital mortality was 13%, with 5% in the normal cTnI group and 28%
      in the intermediate cTnI group. By multivariate analysis, intermediate cTnI was
      independently associated with in-hospital mortality (p = 0.004) and length of ICU
      stay (p = 0.028). The only other independent risk factor for inpatient mortality
      was a standardized ICU prognostic measurement (Simplified Acute Physiology Score
      II score). Intermediate cTnI had no prognostic implications regarding length of
      hospital stay, readmission rate, or postdischarge mortality at 6 months. In
      conclusion, an intermediate level of cTnI in patients without ACS in the ICU is
      an independent prognostic marker predicting in-hospital mortality and length of
      ICU stay. Patients with intermediate cTnI levels who survive to discharge have
      equivalent out-of-hospital courses for up to 6 months compared with patients with
      normal cTnI levels.

PMID- 18721504
TI  - Is coding for myocardial infarction more accurate now that coding descriptions
      have been clarified to distinguish ST-elevation myocardial infarction from non-ST
      elevation myocardial infarction?
AB  - Outcomes are typically graded on the basis of diagnoses coded according to the
      International Classification of Diseases, Ninth Revision (ICD-9). To facilitate
      performance measurement, the ICD-9 codes for acute myocardial infarction changed
      in October 2005 to completely separate non-ST elevation myocardial infarction
      (NSTEMI; code 410.71) and ST elevation myocardial infarction (STEMI; all other
      codes 410.x), yet it is unclear whether these changes have been implemented by
      coders. Patients in the National Registry of Myocardial Infarction (NRMI),
      version 5, were categorized in 2 ways: by electrocardiographic (ECG) findings and
      ICD-9 codes. Agreement between ECG findings and ICD-9 codes for type of
      myocardial infarction (STEMI or NSTEMI) was assessed before and after ICD-9
      revision. Mortality rates were measured in a subgroup of patients discharged
      without transfer after the coding change. There were 102,679 hospitalizations
      before October 2005 and 63,012 hospitalizations after the coding change, among
      which the mean age was 66.7 years. Previously, 81% of NSTEMIs (by ECG diagnosis)
      were coded ICD-9 410.71; after the reclassification of code 410.71 to reflect
      NSTEMI, 82% of NSTEMIs were coded 410.71 (p <0.001). Overall, the correlation of
      ECG diagnosis with ICD-9 code improved only slightly after the coding change. In
      conclusion, despite more distinctly separated definitions of STEMI and NSTEMI in
      the new ICD-9 coding system as of October 2005, there appears to be little change
      in coding, which may reflect a lack of awareness of this substantial change in
      classification.

PMID- 18721505
TI  - Usefulness of paradoxical systolic blood pressure increase after exercise as a
      predictor of cardiovascular mortality.
AB  - Exercise treadmill testing (ETT) is a well-accepted examination for patients with
      suspected coronary artery disease (CAD), and exercise induced ST-segment
      deviation is commonly used for CAD detection. However, recent evidence shows that
      systolic blood pressure (SBP) changes during and after exercise were associated
      with CAD severity, risk of acute myocardial infarction and stroke, new-onset
      hypertension, and even cardiovascular mortality. We retrospectively assessed
      3,054 patients referred for ETT in 1996. Blood pressure and heart rate were
      recorded at rest, during peak exercise, and 1 and 3 min after exercise. SBP at 3
      min of recovery equal to or higher than that at 1-min of recovery was defined as
      paradoxical SBP increase. These patients were categorized into 4 groups according
      to ETT ST-segment change and postexercise SBP change. After 10 years of follow
      up, 346 patients (11%) died, with 129 (4%) dying from cardiovascular disease
      (CVD). Among the 4 groups, patients with ischemic ST-segment change and
      paradoxical SBP increase were associated with a higher risk for mortality, with
      odds ratios of 1.86 (95% confidence interval 1.31 to 2.65) for all-cause
      mortality and 3.18 (95% confidence interval 1.94 to 5.20) for CVD mortality,
      respectively. Patients with isolated paradoxical SBP increase still had a higher
      risk of CVD mortality (odds ratio 1.80, 95% confidence interval 1.70 to 3.04),
      even after controlling other cardiovascular risk factors. In subgroup analysis of
      346 mortality subjects, patients with ischemic ST-segment change and paradoxical
      SBP increase would be more likely to die from CVD. In conclusion, compared with
      ischemic ST-segment change, paradoxical SBP increase after exercise is an
      important and significant predictor of CVD mortality.

PMID- 18721506
TI  - Effectiveness of reloading to overcome clopidogrel nonresponsiveness in patients
      with acute myocardial infarction.
AB  - Whether increasing doses of clopidogrel can overcome nonresponsiveness was
      evaluated. Clopidogrel nonresponsiveness was found in up to 25% of treated
      patients and was associated with worse prognosis in patients with acute coronary
      syndrome and patients undergoing coronary intervention. Adenosine diphosphate
      (ADP)-induced platelet aggregation was prospectively determined on day 4 of acute
      myocardial infarction in 200 consecutive patients, who received clopidogrel 300
      mg as a loading dose and 75 mg/day thereafter. Thirty patients (15%) had ADP
      induced platelet aggregation >or=80% using light transmittance aggregometry and
      were considered clopidogrel nonresponders. Nonresponders were reloaded with
      clopidogrel 600 mg, followed by 150 mg/day for 4 weeks. A 75-mg/day dose was
      resumed thereafter. ADP-induced platelet aggregation was reassessed 4 hours after
      reloading and biweekly for 10 weeks. Flow cytometry was used to determine
      platelet P-selectin expression and fibrinogen binding before and 4 hours after
      reloading. ADP-induced platelet aggregation significantly decreased 4 hours after
      reloading (from 83 +/- 6% to 56 +/- 14%; p <0.01). The decrease in platelet
      aggregation was maintained throughout the 4-week doubled maintenance dose. After
      resuming a maintenance dose of 75 mg/day, ADP-induced platelet aggregation
      returned to 66 +/- 12% (p <0.001), and 5 patients (17%) had ADP-induced platelet
      aggregation >or=80%. Flow cytometry showed a significant decrease in P-selectin
      expression (from 37 +/- 16% to 26 +/- 13%; p <0.01) and fibrinogen binding (from
      84 +/- 7% to 70 +/- 13%; p <0.01) in ADP-stimulated platelets 4 hours after
      reloading. In conclusion, clopidogrel reloading and increased maintenance dose
      may overcome clopidogrel nonresponsiveness in patients with acute myocardial
      infarction.

PMID- 18721507
TI  - Drug-eluting stents versus bare metal stents for narrowing in saphenous vein
      grafts.
AB  - Conflicting data exist regarding an advantage of drug-eluting stents (DES) over
      bare metal stents (BMS) in catheter-based treatment of saphenous vein graft (SVG)
      stenoses. This study was undertaken to compare the efficacy of these modalities
      in that lesion subset. The DES group consisted of 138 cases with 183 lesions
      (sirolimus-eluting stents, n = 117; paclitaxel-eluting stents, n = 66) and the
      BMS group consisted of 344 cases with 478 lesions that were followed to 1 year.
      We examined a composite end point that comprised death, Q-wave myocardial
      infarction, and target lesion revascularization. More BMS were deployed per
      patient (p <0.001) and the diameters of BMS deployed was significantly greater (p
      <0.001). Peak postprocedure values of creatine kinase-MB (p = 0.003) and troponin
      I (p = 0.05) were higher in BMS. At 1 year there was no significant superiority
      of DES over BMS with regard to hard end points (death and Q-wave myocardial
      infarction). In conclusion, this study indicates that both DES and BMS for SVG
      disease provide acceptably safe and efficacious results, but unlike the case in
      native coronary arteries, DES use does not reduce the frequency of the need for
      repeat revascularization.

PMID- 18721508
TI  - Impact of optimal medical therapy and revascularization on outcome of patients
      with chronic kidney disease and on dialysis who presented with acute coronary
      syndrome.
AB  - Coronary artery disease is the main cause of death in patients with chronic
      kidney disease (CKD). The poor prognosis associated with acute coronary syndrome
      (ACS) in these patients has been related to therapeutic nihilism. This study
      included 2,357 patients with ACS who had percutaneous coronary intervention.
      According to their creatinine clearance and medical history, they were divided
      into 3 groups: dialysis (n = 73); CKD (n= 293); and control (n= 1,991). Rates of
      cardiovascular events were recorded during a 1-year follow-up period. Patients in
      all groups received similar contemporary therapy for ACS, including percutaneous
      coronary intervention and optimal medial therapy. On admission, patients with CKD
      and patients on dialysis more often presented with cardiogenic shock (p = 0.05
      and 0.02, respectively). A graded increase in the rate of major adverse
      cardiovascular events at 1 year was observed with decreasing renal function
      (control 13%, CKD 22.9%, dialysis 45.2%, p <0.001 for all comparisons). In
      multivariate analysis, patients with CKD and on dialysis were significantly
      associated with 1-year major adverse cardiac events with adjusted hazard ratios
      of, respectively, 1.5 (95% confidence interval 1.1 to 2.1; p = 0.009) and 2.7
      (95% confidence interval 1.7 to 4.1; p <0.001). In conclusion, despite optimal
      contemporary medical therapy and revascularization, the prognosis of patients
      with CKD and, in particular, of patients undergoing dialysis, remains poor.

PMID- 18721509
TI  - A clinical risk score for prediction of stent thrombosis.
AB  - The aim was to develop a clinically useful patient risk score predictive for
      stent thrombosis (ST). Using readily available baseline clinical and angiographic
      characteristics, a Cox proportional hazards multivariate model was used to
      identify significant (p <0.10) predictors of ST through 1 year in 2,487 patients
      receiving a TAXUS Express (Boston Scientific Corp., Natick, Massachusetts) drug
      eluting stent (DES) in the ARRIVE 1 registry. Hazard ratios of significant
      predictors were rounded to an integer value ranging from 2 to 5. These values
      were summed for a maximum possible score of 24. The model was validated using 1
      year data from a similar DES data set (ARRIVE 2, n = 4,820 patients). The 8
      significant predictors found were thienopyridine therapy discontinuation before 6
      months, insulin-requiring diabetes, smoker at baseline, left main stent
      placement, multiple stent placement, lesion length >28 mm, moderate to severe
      lesion calcification, and reference vessel diameter <3 mm. Model discrimination
      was high, indicated by an area under the receiver-operator characteristic curve
      of 0.819. Stratification of patients into low-, medium-, and high-risk groups
      showed that ST developed in 0.8% of patients with a score <6, 3.6% of patients
      with a score of 7 to 13, and 12.6% of patients with a score >or=14. In
      conclusion, using 8 readily available clinical and angiographic characteristics,
      we defined an ST risk score for patients receiving a DES during the first year.
      Analysis of patients from ARRIVE 1 and 2 showed that most (73%) were in the
      lowest risk category, with 25% in the moderate risk category. Less than 2% were
      at highest risk of developing ST.

PMID- 18721510
TI  - Impact of perioperative myocardial infarction on angiographic and clinical
      outcomes following coronary artery bypass grafting (from PRoject of Ex-vivo Vein
      graft ENgineering via Transfection [PREVENT] IV).
AB  - Myocardial infarction (MI) after coronary artery bypass grafting (CABG) is
      associated with significant morbidity and mortality. Frequency, management,
      mechanisms, and angiographic and clinical outcomes associated with perioperative
      MI remain poorly understood. PREVENT IV was a multicenter, randomized, placebo
      controlled trial of edifoligide in 3,014 patients undergoing CABG. Angiographic
      and 2-year clinical follow-up were complete for 1,920 and 2,956 patients,
      respectively. Perioperative MI was defined as creatinine kinase-MB increase
      >or=10 times the upper limit of normal or >or=5 times the upper limit of normal
      with new 30-ms Q waves within 24 hours of surgery. Baseline characteristics, in
      hospital management, and angiographic and clinical outcomes of patients with and
      without perioperative MI were compared. Perioperative MI occurred in 294 patients
      (9.8%). Patients with perioperative MI had longer surgery (250 vs 230 minutes; p
      <0.001), more on-pump surgery (83% vs 78%; p = 0.048), and worse target-artery
      quality (p <0.001). Patients with perioperative MI more frequently underwent
      angiography within 30 days of enrollment (1.7% vs 0.6%; p = 0.021). One-year
      angiographic vein graft failure occurred in 62.4% of patients with and 43.8% of
      patients without perioperative MI (p <0.001). Two-year composite clinical outcome
      (death, MI, or revascularization) was worse in patients with perioperative MI
      before (19.4% vs 15.2%; p = 0.039) and after (hazard ratio 1.33, 95% confidence
      interval 1.00 to 1.76, p = 0.046) adjusting for differences in significant
      predictors. In conclusion, perioperative MI was relatively common, was associated
      with worse outcomes, and mechanisms other than vein graft failure accounted for a
      substantial proportion of these MIs. Further research is needed into the
      prevention and treatment of perioperative MI in patients undergoing CABG.

PMID- 18721511
TI  - Outcomes of patients with acute coronary syndrome and previous coronary artery
      bypass grafting (from the Pravastatin or Atorvastatin Evaluation and Infection
      Therapy [PROVE IT-TIMI 22] and the Aggrastat to Zocor [A to Z] trials).
AB  - We examined the effects of intensive statin therapy in patients with acute
      coronary syndromes (ACSs) and previous coronary artery bypass graft surgery
      (CABG) participating in the Pravastatin or Atorvastatin Evaluation and Infection
      Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE-IT TIMI 22) and the
      Aggrastat to Zocor (A to Z) trials. Of the 8,655 patients enrolled in PROVE IT
      TIMI 22 or A to Z, 640 (7.4%) had undergone CABG before enrollment. After a
      median follow-up of 2 years, compared with patients without previous CABG, those
      with previous CABG had a higher risk of cardiovascular death (6.2% vs 2.8%),
      myocardial infarction (14.2% vs 6.6%), and readmission for ACS (7.9% vs 4.4%, p
      <0.001 for all comparisons) but a lower rate of repeat coronary revascularization
      (22.7% vs 26.9%, p = 0.01). Compared with moderate statin therapy, intensive
      statin therapy appeared to decrease the composite of cardiovascular death,
      myocardial infarction, stoke, and readmission for an ACS (A to Z primary end
      point) to a similar extent in patients with (26.1% vs 21.6%, hazard ratio 0.84, p
      = 0.27) and without (13.9% vs 12.0%, hazard ratio 0.86, p = 0.016) previous CABG,
      although the decrease was not statistically significant in the previous CABG
      group, likely due to the small number of patients with previous CABG. In
      conclusion, compared with patients with ACS without previous CABG, those with
      previous CABG have a higher risk for adverse cardiac events and may derive
      similar benefit from intensive statin therapy.

PMID- 18721512
TI  - The editor's roundtable: lipid management beyond statins-reducing residual
      cardiovascular risk.

PMID- 18721513
TI  - Changing trends of hospital utilization in patients after their first episode of
      atrial fibrillation.
AB  - A marked increase in hospitalization for patients with atrial fibrillation (AF)
      has previously been noted. Whether this increase is related to a change in the
      prevalence of AF or a change in the pattern of practice with respect to the
      management of AF remains unclear. To determine the trends in hospital utilization
      after first AF in a community-based setting (Olmsted County, Minnesota),
      residents diagnosed with first AF from 1980 to 2000 were identified and followed
      until 2004. The primary outcome of interest was hospital admission for
      cardiovascular reasons. Of a total of 4,498 subjects (73 +/- 14 years old, 51%
      men), 2,503 (56%) were admitted to the hospital for cardiovascular causes >or=1
      time during a mean follow-up of 5.5 +/- 5.0 years. Risk of first hospitalization
      was greatest during the first year of AF (cumulative incidence 31%, 95%
      confidence interval [CI] 30 to 32). First hospitalization was strongly related to
      age (p <0.0001) but not to sex (p = 0.38). From 1980 to 2000, the age-and sex
      adjusted rate of first hospitalization increased, on average, by 2.5% a year (95%
      CI 1.8 to 3.2, p <0.0001), even after multivariable adjustment for co
      morbidities. When we excluded all hospital admissions for the purposes of AF
      management, the increase in hospitalization was only 0.8% per year (95% CI 0.05
      to 1.6, p = 0.04), which was no longer significant after multivariable adjustment
      for co-morbidities (p = 0.25). In conclusion, the marked increase in
      hospitalization after first AF diagnosis from 1980 to 2000 appeared to be largely
      driven by the changing practice pattern in AF management.

PMID- 18721514
TI  - Usefulness of P-wave dispersion in standard twelve-lead electrocardiography to
      predict transition from paroxysmal to persistent atrial fibrillation.
AB  - A prospective study was conducted to investigate the validity of the hypothesis
      that P-wave dispersion (Pd) may be a clinically useful predictor of progression
      from paroxysmal to persistent atrial fibrillation (AF). Two hundred four
      consecutive patients with a diagnosis of paroxysmal AF were studied. Standard 12
      lead electrocardiography and echocardiography were performed on all patients at
      the time of entry into the study. Pd was measured as the difference between
      maximum and minimum P-wave duration in any of the 12 leads. Mean follow-up was 66
      +/- 8 months. Group I included patients (n = 132) in whom paroxysmal AF did not
      progress to persistent AF, and group II included those (n = 72) who developed
      persistent AF. In group II, age, percentage of men, percentage of patients with
      diabetes mellitus, maximum P-wave duration, Pd, and left atrial dimension were
      significantly higher than in group I (p <0.05). Multivariate logistic regression
      analysis using these 6 factors identified age (odds ratio 2.18, 95% confidence
      interval 1.41 to 3.41, p <0.01) and Pd (odds ratio 1.91, 95% confidence interval
      1.51 to 2.44, p <0.01) as independent predictors of a transition to persistent
      AF. Pd >or=40 ms predicted progression to persistent AF with sensitivity of 71%,
      specificity of 77%, positive predictive value of 63%, negative predictive value
      of 83%, and accuracy of 75%. In conclusion, Pd was a clinically useful predictor
      of progression from paroxysmal to persistent AF.

PMID- 18721515
TI  - Evaluation of catheter ablation of periatrial ganglionic plexi in patients with
      atrial fibrillation.
AB  - Recent data suggests that the cardiac autonomic nervous system has an important
      role in the initiation and maintenance of atrial fibrillation (AF). This study
      investigated (1) the feasibility of identifying and targeting these autonomic
      ganglia using endocardial radiofrequency stimulation and ablation, respectively;
      (2) the efficacy of endocardial ablation to completely eliminate the vagal
      response elicited from epicardial stimulation; and (3) the effect of autonomic
      ablation on the acute inducibility of AF. The study included 18 patients referred
      for catheter ablation of suspected vagal-mediated AF. The endocardial left atrial
      surface was stimulated at high frequency (20 to 50 Hz) to elicit a vagal
      response. In selected patients (n = 5), pericardial access was obtained using a
      subxyphoid puncture to permit epicardial stimulation. Catheter ablation of the
      putative autonomic ganglionic sites was performed from the left atrial
      endocardium using irrigated radiofrequency energy. After ablation of all
      identifiable autonomic ganglia, high-frequency pacing was repeated to induce AF.
      In all patients, stimulation at certain endocardial sites elicited a vagal
      response. Endocardial ablation abrogated this vagal responsiveness. Furthermore,
      for sites accessible from the pericardium, the vagal response elicited using
      epicardial stimulation was also eliminated. Despite successful ablation of these
      ganglia, AF was still inducible in 17 of 18 patients. In conclusion, successful
      ablation of autonomic ganglia from an endocardial approach can be reliably
      achieved using an irrigated catheter. In addition, ablation of these structures
      in patients with vagal-mediated AF is insufficient to prevent its acute
      reinduction with high-frequency atrial stimulation.

PMID- 18721516
TI  - Prognosis of subjects with Brugada-type electrocardiogram in a population of
      middle-aged Japanese diagnosed during a health examination.
AB  - There is controversy about the clinical significance of an incidental finding of
      a Brugada-type electrocardiogram (ECG) pattern. To assess the prognosis of
      subjects with a diagnosis of a Brugada-type ECG pattern during a health
      examination, 13,904 subjects (mean age 58 +/- 10 years) who had the annual health
      examination including an ECG offered to adult citizens of Moriguchi City, Osaka,
      Japan, in 1997 were studied. A Brugada-type ECG pattern was found in 98 subjects,
      and 37 subjects had type 1. During a mean follow-up of 7.8 +/- 1.6 years, there
      were 4 deaths (4.1%) and 1 cardiovascular death (1.0%) in subjects with a Brugada
      type ECG pattern, whereas there were 612 deaths (4.4%) and 142 cardiovascular
      deaths (1.0%) in those without. One cardiovascular death in a subject with a
      Brugada-type ECG pattern was sudden death. Unadjusted proportional hazards
      regression analyses showed that Brugada-type ECG pattern was not associated with
      either all-cause (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.34 to
      2.41) or cardiovascular mortality (HR 0.97, 95% CI 0.14 to 6.93). After
      adjustment for cardiovascular risk factors, Brugada-type ECG pattern had no
      association with either all-cause (HR 0.77, 95% CI 0.29 to 2.07) or
      cardiovascular mortality (HR 1.01, 95% CI 0.14 to 7.31). In conclusion, Brugada
      type ECG patterns diagnosed during a health examination in a middle-aged
      population had a low risk of sudden death and were not associated with increased
      risk of either cardiovascular or all-cause mortality.

PMID- 18721517
TI  - Cost of preimplantation cardiac imaging in patients referred for a primary
      prevention implantable cardioverter-defibrillator.
AB  - Recent guidelines have focused on ejection fraction cut-off values to determine
      eligibility for primary-prevention implantable cardioverter-defibrillators
      (ICDs). Clinical trials that led to the guidelines used varying techniques for
      ejection fraction assessment, including echocardiography and multigated
      acquisition (MUGA) scan. A prospective cohort study to determine the economic
      attractiveness of repeated echocardiography and MUGA scanning during the
      evaluation process of patients referred for consideration of a primary-prevention
      ICD was undertaken. From January 2005 to December 2006, data were collected for
      patients aged >18 years with ejection fraction <30% referred for a primary
      prevention ICD based on referral assessment of heart function in any form. Costs
      based on the 2006 Ontario Health Insurance Plan fee schedule were determined for
      clinical assessment, echocardiography, MUGA scanning, and ICD implantation in
      patients who remained eligible based on MUGA ejection fraction. The 100 patients
      (age 61.1 +/- 10.2 years; 78 men) assessed for primary-prevention ICD
      implantation had an ejection fraction of 28.9 +/- 12.3% using MUGA scan. Thirty
      one of 100 patients (31%) had an ejection fraction >30% and were no longer
      eligible for an ICD. Although imaging increased preimplantation cost from dollars
      130 to dollars 536 per patient, averted inappropriate ICDs decreased the overall
      per-patient cost from dollars 20,914 to dollars 14,877. Despite an additional
      testing cost of dollars 40,599, the overall cost savings was dollars 603,722 in
      the 100 patients, with a cost savings of dollars 6,037 per patient. In
      conclusion, verification of ejection fraction identified a significant proportion
      of patients who were not eligible for an ICD.

PMID- 18721519
TI  - Measures of left ventricular dyssynchrony and the correlation to clinical and
      echocardiographic response after cardiac resynchronization therapy.
AB  - There is still no standardized measure of left ventricular (LV) dyssynchrony or
      definition of response in candidates of cardiac resynchronization therapy (CRT).
      Recipients of CRT underwent echocardiographic assessment of LV dyssynchrony
      before and immediately after implantation of a CRT device. Patients were followed
      for 6 months postimplantation. A total of 44 patients (64 +/- 12 years, 30 men,
      and 26 with ischemic cardiomyopathy) were included in this analysis. There was a
      significant decrease in both radial (304 +/- 137 vs 121 +/- 85 ms, p <0.001) and
      longitudinal (143 +/- 104 vs 95 +/- 43 ms, p = 0.02) measures of LV dyssynchrony
      immediately after CRT. The immediate post-CRT change in radial (r = -0.43, p =
      0.015) but not longitudinal (r = -0.09, p = 0.61) LV dyssynchrony correlated with
      a significant improvement in the physical component of the quality-of-life score
      6 months after CRT. Although a higher baseline longitudinal (p = 0.05) or radial
      (p = 0.025) LV dyssynchrony predicted a >or=1 improvement in New York Heart
      Association classification of heart failure 6 months after CRT, acute changes in
      neither radial (p = 0.71) nor longitudinal (p = 0.89) LV dyssynchrony were
      predictive of any improved echocardiographic outcomes in follow-up. Concordance
      between clinical and echocardiographic response to CRT was documented in 72% of
      patients. In conclusion, both longitudinal and radial measures of LV dyssynchrony
      improve after CRT. The change in longitudinal but not radial measures of LV
      dyssynchrony correlates with improved physical quality-of-life score in
      intermediate term follow-up.

PMID- 18721518
TI  - Alcohol consumption and heart failure in hypertensive US male physicians.
AB  - Although alcohol drinking increases blood pressure and heavy drinking has been
      associated with alcoholic cardiomyopathy, little is known about the association
      between light to moderate drinking and risk of heart failure (HF) in hypertensive
      subjects. Thus, the association between light to moderate drinking and incident
      HF in 5,153 hypertensive male physicians who were free of stroke, myocardial
      infarction, or major cancers at baseline was prospectively examined. Alcohol
      consumption was self-reported and classified as <1, 1 to 4, 5 to 7, and >or=8
      drinks/week. HF was ascertained using follow-up questionnaires and validated
      using Framingham criteria. Average age was 58 years, and about 70% of subjects
      consumed 1 to 7 drinks/week. A total of 478 incident HF cases occurred in this
      cohort during follow-up. Compared with subjects consuming <1 drink/week, hazard
      ratios for HF were 0.89 (95% confidence interval [CI] 0.70 to 1.12), 0.72 (95% CI
      0.57 to 0.91), and 0.38 (95% CI 0.20 to 0.72) for alcohol consumption of 1 to 4,
      5 to 7, and >or=8 drinks/week after adjustment for age, body mass index, smoking,
      randomization group, use of multivitamins, vegetable consumption, breakfast
      cereal, exercise, and history of atrial fibrillation, respectively (p for trend
      <0.001). Similar results were obtained for subjects with HF with and without
      antecedent myocardial infarction and those without diabetes mellitus. In
      conclusion, our data suggested that light to moderate alcohol consumption was
      associated with a lower risk of HF in hypertensive male physicians.

PMID- 18721520
TI  - Relation of left ventricular systolic dyssynchrony in patients with heart failure
      to left ventricular ejection fraction and to QRS duration.
AB  - Left ventricular (LV) systolic dyssynchrony is an important pathologic mechanism
      in patients with heart failure (HF). However, the prevalence of intraventricular
      dyssynchrony in patients with different LV ejection fractions (EFs) is unknown.
      This study evaluated 402 consecutive patients with HF (mean age 64.99 +/- 13.15
      years, 72.4% men) and 120 healthy controls. Dyssynchrony indexes included the SD
      of the time to peak systolic velocity (Ts) in ejection phase in the 12-segmental
      model (Ts-SD) and the difference in Ts between basal septal and basal lateral
      segments (Ts-Septal-Lateral) using tissue Doppler imaging. Patients were divided
      into 3 groups according to LVEF (LVEF <20%, >20% to 35%, and >35% to 50%) and
      compared with healthy controls. Both indexes were significantly higher in all 3
      LVEF groups compared with controls (p <0.0001). Based on the established cut-off
      values, systolic dyssynchrony was equally prevalent in all 3 LVEF groups and was
      67%, 62%, and 55% using Ts-SD and 38%, 36%, and 35% using Ts-Septal-Lateral,
      respectively. However, the prevalence of systolic dyssynchrony was higher using
      Ts-SD than Ts-Septal-Lateral (chi-square = 94.43, p <0.001). Conversely, the
      prevalence of electrical dyssynchrony, defined as a >120-ms QRS duration,
      decreased significantly with increasing LVEF (44%, 35%, and 16%; chi-square 5.60,
      p <0.001). In conclusion, the prevalence of mechanical systolic dyssynchrony was
      independent of severity of LV systolic dysfunction. This may implicate the
      potential role of cardiac resynchronization therapy for those with LVEF of 35% to
      50%, in particular when systolic dyssynchrony is present.

PMID- 18721521
TI  - Relation of serum heat shock protein 60 level to severity and prognosis in
      chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.
AB  - Heat shock protein (HSP) 60 is induced by a variety of stressors, including
      oxidative stress and inflammation, and it plays a protective role against stress
      induced cardiomyocyte injury. Recently, it has been reported that HSP 60 exists
      in the circulation. Chronic heart failure (CHF) is characterized by systemic
      abnormalities, and the myocardium is exposed to various stressors. However, the
      clinical significance of serum HSP 60 has not been examined in CHF. Therefore,
      the purpose of this study was to examine whether HSP 60 is correlated with the
      severity of CHF and whether HSP 60 can predict clinical outcomes in patients with
      CHF. Serum HSP 60 levels were measured in 112 patients with CHF and 62 control
      subjects. Serum HSP 60 levels were higher in patients with CHF than in control
      subjects and increased with advancing New York Heart Association functional
      class. There were 37 cardiac events during a mean follow-up period of 569 +/- 476
      days (range 17 to 1,986). Serum HSP 60 levels were higher in patients with
      cardiac events than in event-free patients. Patients were divided into 4 groups
      on the basis of HSP 60 level. Cox proportional-hazards regression analysis and
      Kaplan-Meier analysis revealed that the fourth quartile was associated with the
      greatest risk for cardiac events. In conclusion, serum HSP 60 level was related
      to the severity of CHF and associated with a high risk for adverse cardiac events
      in patients CHF.

PMID- 18721522
TI  - Effect of Beta-blocker therapy on survival in patients with severe mitral
      regurgitation and normal left ventricular ejection fraction.
AB  - Chronic volume overload from chronic severe mitral regurgitation (MR) results in
      neuroendocrine activation similar to the heart failure syndrome despite normal
      left ventricular (LV) ejection fraction (EF). Hence, the hypothesis that beta
      blocker (BB) therapy may have a beneficial effect in these patients was tested
      using a large observational cohort. Our echocardiographic database was searched
      for patients with severe MR and normal LVEF. Full chart reviews were conducted
      for clinical and pharmacologic data. Survival was analyzed as a function of BB
      therapy. The search produced 895 patients aged 68 +/- 17 years, 44% men, with
      LVEF 66 +/- 7%. Of these, 32% were on BB therapy. Use of a BB was associated with
      a significantly decreased mortality hazard of 0.62 (95% confidence interval 0.46
      to 0.83, p = 0.002), which was unchanged after adjusting for age, gender, LVEF,
      coronary artery disease, diabetes mellitus, hypertension, and cardiac valve
      surgery. The independent beneficial effect of BBs was seen in patients with or
      without coronary artery disease, those with or without hypertension, and patients
      managed both medically and surgically. In conclusion, use of BB therapy was
      associated with a significant independent survival benefit in patients with
      chronic severe MR with normal LVEF. This benefit was seen in patients with or
      without coronary artery disease, as well as patients managed both medically and
      surgically. Use of BBs in patients with severe MR despite normal LVEF is
      suggested.

PMID- 18721523
TI  - Differentiation of hypertrophic cardiomyopathy from other forms of left
      ventricular hypertrophy by means of three-dimensional echocardiography.
AB  - In clinical practice, differential diagnosis among different forms of left
      ventricular (LV) hypertrophy is not always easy, and hypertrophic cardiomyopathy
      (HC) can be misdiagnosed. In this study, it was hypothesized that a 3-dimensional
      echocardiographically derived index of LV regional mass distribution could be
      useful in differentiating HC from other forms of LV hypertrophy. Sixty-eight
      subjects underwent 2- and 3-dimensional echocardiography; of these, 20 were
      healthy volunteers, 18 were top-level athletes, 15 had essential hypertension,
      and 15 had HC. In off-line analysis, a 12-segment model was generated for
      segmental mass measurement. A mass dispersion index (MDI) was calculated as the
      average of the SDs of segmental mass values at the basal, middle, and apical
      layers. The ratio of ventricular septal thickness to posterior wall thickness was
      also calculated using 2-dimensional echocardiography. Patients with HC had
      significantly higher MDI values (1.75 +/- 0.43) than healthy volunteers (0.39 +/-
      0.13) (p <0.0001), athletes (0.49 +/- 0.12) (p <0.0001), and patients with
      hypertension (0.38 +/- 0.10) (p <0.0001). The ratio of ventricular septal
      thickness to posterior wall thickness was significantly higher in patients with
      HC (1.31 +/- 0.23) than normal subjects (1.04 +/- 0.05) (p <0.0001), highly
      trained athletes (1.03 +/- 0.06) (p = 0.001), and patients with hypertension
      (1.06 +/- 0.06) (p = 0.002). However, receiver-operating characteristic analysis
      showed a higher sensitivity for MDI (93.3% for the cut-off value of 1.13) than
      the ratio of ventricular septal thickness to posterior wall thickness (66.7% for
      the cut-off value of 1.20), with excellent specificity for both (100%) in
      identifying patients with HC. In conclusion, the 3-dimensional
      echocardiographically derived MDI could be considered a useful and reliable
      additional tool in differentiating HC from other forms of LV hypertrophy.

PMID- 18721524
TI  - Effect of alcohol septal ablation in patients with hypertrophic cardiomyopathy on
      the electrocardiographic pattern.
AB  - Alcohol septal ablation (ASA) of patients with hypertrophic cardiomyopathy (HC)
      allows study of the electrocardiographic effects of myocardial necrosis confined
      to the base of the interventricular septum, a rare event in atherothrombotic
      coronary artery disease. Eighty-four consecutive patients were studied after ASA
      for HC. After excluding 20 with pacing before ASA and 6 with no available
      preprocedure electrocardiograms, the electrocardiograms of the remaining 58
      patients were compared with those of 58 consecutive patients with anterior ST
      elevation myocardial infarctions who underwent primary intervention for left
      anterior descending coronary artery (LAD) occlusions. In 25 patients, the
      occlusions were proximal to the first septal perforator, and in 33 patients, the
      occlusions were more distal. All electrocardiograms were analyzed with respect to
      conduction abnormalities and ST-segment changes. Patients with HC developed right
      bundle branch block significantly more often than those with LAD occlusions (50%
      vs 14%, p = 0.001) Moreover, patients with HC required postprocedure pacing more
      frequently (14% vs 2%, p <0.05). A distinctive pattern of ST displacement was
      found. There was more frequent ST depression in leads I and aVF and greater ST
      elevation in lead V(1) in patients who underwent ASA, indicating a greater
      tendency toward a rightward direction than was true in patients with LAD
      occlusions. In conclusion, in addition to more frequent right bundle branch block
      after ASA, a distinctive a characteristic pattern of ST-segment deviation similar
      to but distinct from that produced by proximal LAD occlusion appeared.

PMID- 18721525
TI  - Prevalence and determinants of anemia in adults with complex congenital heart
      disease and ventricular dysfunction (subaortic right ventricle and single
      ventricle physiology).
AB  - Anemia is well recognized as a marker of poor prognosis in patients with acquired
      heart disease and heart failure. Adults with complex congenital heart disease and
      ventricular dysfunction (subaortic right ventricle or single-ventricle
      physiology) represent a different population, because they are typically much
      younger and have less co-morbidity compared with patients with acquired forms of
      heart disease. The purpose of this study was to evaluate the prevalence and
      determinants of anemia in this population. Baseline hemoglobin levels were
      recorded at the time of the initial clinic visit, and final hemoglobin levels
      were those recorded before death or transplantation or at study completion.
      Anemia was defined as hemoglobin <135 g/L in men and <120 g/L in women. One
      hundred sixty-seven patients (100 men, mean age 34 +/- 8 years, mean ejection
      fraction 35 +/- 9%) were included, 66 with atrial switch operations, 42 with
      congenitally corrected transposition of the great arteries, and 59 with Fontan
      physiology. The mean hemoglobin level at baseline was 149 +/- 22 g/L and at
      follow-up was 139 +/- 29 g/L. The overall prevalence of anemia was 29% at
      completion. Hyponatremia, decreased renal function, and the use of warfarin were
      independent predictors of anemia. In conclusion, anemia is common in patients
      with complex congenital heart disease and ventricular dysfunction, in particular
      those with Fontan physiology.

PMID- 18721526
TI  - Absence of TGFBR1 and TGFBR2 mutations in patients with bicuspid aortic valve and
      aortic dilation.
AB  - Mutations in the genes encoding transforming growth factor-beta receptor types I
      and II (TGFBR1 and TGFBR2, respectively) are commonly identified in patients with
      Loeys-Dietz syndrome, as well as some patients with Marfan's syndrome or familial
      thoracic aortic aneurysms and dissections. This suggests that there is
      considerable phenotypic heterogeneity associated with mutations in these genes.
      Because bicuspid aortic valve (BAV) is a congenital heart defect in patients with
      Loeys-Dietz syndrome, this study was conducted to investigate whether variants in
      TGFBR1 or TGFBR2 are responsible for sporadic BAV. Analysis of these genes in 35
      patients with BAVs identified only known single-nucleotide polymorphisms or novel
      synonymous or intronic substitutions. In conclusion, mutations in TGFBR1 and
      TGFBR2 rarely cause sporadic BAV.

PMID- 18721527
TI  - Relation of cardiac troponin I levels with in-hospital mortality in patients with
      ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.
AB  - Troponin I levels were drawn within 24 hours of stroke in 161 of 175 patients
      (92%) with ischemic stroke, 94 of 107 patients (88%) with intracerebral
      hemorrhage, and 96 of 96 patients (100%) with subarachnoid hemorrhage. A troponin
      level >0.4 ng/ml was considered increased. In patients with ischemic stroke, in
      hospital mortality occurred in 15 of 23 patients (65%) with increased troponin I
      compared with 6 of 138 patients (4%) with normal troponin I (p <0.001). In
      patients with intracerebral hemorrhage, in-hospital mortality occurred in 9 of 14
      patients (64%) with increased troponin I compared with 22 of 80 patients (28%)
      with normal troponin I (p <0.005). In patients with subarachnoid hemorrhage, in
      hospital mortality occurred in 8 of 20 patients (40%) with increased troponin I
      compared with 8 of 76 patients (11%) with normal troponin I (p <0.005). In
      conclusion, patients with ischemic stroke, intracerebral hemorrhage, and
      subarachnoid hemorrhage with elevated troponin I levels have increased in
      hospital mortality.

PMID- 18721528
TI  - Cardiovascular manifestations in human immunodeficiency virus-infected patients.
AB  - Human immunodeficiency virus (HIV) is now a pandemic. It afflicts multiple
      organs, including the cardiovascular system. This occurs by direct invasion as
      well as opportunistic infections complicating acquired immunodeficiency syndrome.
      The presence of newer highly active antiretroviral therapy has led to longer
      survival of patients infected with HIV, but the cardiac abnormalities related to
      HIV have remained less well characterized. It is now evident that cardiac
      involvement in patients with acquired immunodeficiency syndrome is relatively
      common. This includes coronary artery disease, dilated cardiomyopathy,
      pericardial effusion, pulmonary hypertension, and ill effects of highly active
      antiretroviral therapy in the form of lipodystrophy, lipoatrophy, and
      dyslipidemia. In fact, HIV can now be viewed as a potential risk factor for
      coronary artery disease, and the dilemma facing clinicians is how to quantify
      this risk. Awareness of accelerated coronary artery disease and dilated
      cardiomyopathy is critical to implement preventive measures early in the course
      of HIV. However, better guidelines are still needed on the basis of prospective
      randomized controlled studies involving large populations. In conclusion, this
      review describes cardiac abnormalities associated with HIV, including possible
      molecular mechanisms. The co-morbid sequelae, their presentation, and
      pharmacologic management are also discussed.

PMID- 18721529
TI  - Hepatocellular carcinoma with intracavitary cardiac involvement: a case report
      and review of the literature.
AB  - A 71-year-old man with hepatocellular carcinoma (HCC) presented with
      intracavitary cardiac involvement detected incidentally on surveillance computed
      tomography. Tumor with associated thrombus was found to extend from the liver
      through the inferior vena cava into the right atrium. This intracardiac mass
      prolapsed intermittently into the right ventricle, causing functional tricuspid
      stenosis. The mass was resected but recurred after 4 months, eventually causing
      refractory right-sided heart failure. This case illustrates how intracavitary
      cardiac involvement of HCC can develop insidiously and confer significant
      hemodynamic compromise. A review of the published research, including postmortem
      studies, demonstrates that the frequency of intracardiac mass lesions in HCC is
      not insignificant. In conclusion, early detection and diagnosis may have
      increasing importance in the advent of new therapies for treating advanced HCC.

PMID- 18721530
TI  - Effects of intravenous glucagon-like peptide-1 on glucose control and
      hemodynamics after coronary artery bypass surgery in patients with type 2
      diabetes.

PMID- 18721531
TI  - Psoriasis, inflammation, and atrial fibrillation.

PMID- 18721532
TI  - Application of laser ablation inductively coupled plasma mass spectrometry for
      the isotopic analysis of single uranium particles.
AB  - The paper describes the application of laser ablation inductively coupled plasma
      mass spectrometry (LA-ICP-MS) for the isotopic analysis of individual uranium
      oxide particles. The procedure developed is suitable for the accurate measurement
      of 234U, 235U, 236U and 238U isotopes in single actinide particles with lateral
      dimensions down to 10 microm. The 235U/238U isotope ratios can be obtained with a
      precision of a few percent relative standard deviation using a single collector
      ICP-MS instrument. The precision could be improved by the use of slow ablation
      and by taking several LA-ICP-MS replicate spectra on the same particle
      investigated. For the minor isotopes use of higher mass resolution (R=4000) was
      necessary in some cases to avoid spectral interferences. The technique developed
      offers a rapid and accurate possibility for the isotopic composition
      determination of uranium-containing individual particles in environmental and
      safeguards samples.

PMID- 18721533
TI  - Highly improved electrocatalytic behavior of sulfite at carbon ionic liquid
      electrode: application to the analysis of some real samples.
AB  - The electrocatalytic oxidation of sulfite was investigated at carbon ionic liquid
      electrode (CILE). This electrode is a very good alternative to previously
      described electrodes because the electrocatalytic effect is achieved without any
      electrode modification. Comparative experiments were carried out using carbon
      paste electrode (CPE) and glassy carbon electrode (GCE). At CILE, highly
      reproducible and well-defined cyclic voltammograms were obtained for sulfite with
      a peak potential of 0.55 V vs. Ag/AgCl. Sulfite oxidation at CILE does not result
      in deactivation of the electrode surface. The kinetic parameters for this
      irreversible heterogeneous electron transfer process were determined. Under
      optimal experimental conditions, the peak current response increased linearly
      with sulfite concentration over the range of 6-1000 microM. The detection limit
      of the method was 4 microM. The method was applied to the determination of
      sulfite in mineral water, grape juice and non-alcoholic beer samples.

PMID- 18721535
TI  - Use of hydrogen peroxide to achieve interference-free stripping voltammetric
      determination of copper at the bismuth-film electrode.
AB  - In this work, a new approach is presented to allow interference-free
      determination of Cu (II) by stripping voltammetry using the bismuth-film
      electrode. The addition of hydrogen peroxide to the electroanalytical cell has
      promoted complete resolution between re-dissolution peaks of Bi (III) and Cu
      (II). The absence of interference could be evaluated by the correlation
      coefficient (r>0.99) between Cu (II) concentration and its shifted current peak
      (at +212 mV) while achieving a slightly fluctuation of the bismuth current peak
      at -180 mV. Studies were performed aiming towards the optimum conditions for
      trace determination of Cu (II) using hydrogen peroxide. The methodology was
      applied to a real sample (sugarcane spirits) and the results were compared to
      those from graphite furnace atomic absorption spectrometry. The analytical
      parameters of merit and the results of the analysis indicated that the analytical
      methodology could be readily used for trace determination of Cu (II).

PMID- 18721534
TI  - Enhanced anodic Ru(bpy)3(2+) electrogenerated chemiluminescence by polyphenols.
AB  - Anodic Ru(bpy)3(2+) electrogenerated chemiluminescence (ECL) can be enhanced by
      polyphenols in alkaline solution. Spin trapping-electron spin resonance (ESR)
      experiments verified that reactive oxygen species (ROS) were generated during the
      electrolysis of Ru(bpy)3(2+) in alkaline solution, and oxidation of quercetin
      enhanced Ru(bpy)3(2+) ECL at anodic potential by producing additional ROS. This
      ECL enhancement can be used to analyze real sample and evaluate antioxidant
      activity of polyphenols.

PMID- 18721536
TI  - Determination of metacrate in water samples using dispersive liquid-liquid
      microextraction and HPLC with the aid of response surface methodology and
      experimental design.
AB  - An improved method for the determination of metacrate in water samples has been
      developed using dispersive liquid-liquid microextraction (DLLME) prior to liquid
      chromatography analysis. The variables of interest, such as the volume of
      extraction solvent and disperser solvent, salt effect, sample volume, and
      extraction time in the DLLME process, were optimized with the aid of response
      surface methodology and experimental design (RSM). Firstly, an orthogonal array
      design (OAD) was used to choose the significant variables for the optimization.
      Secondly, the significant factors were optimized by using a central composite
      design (CCD) and the quadratic model between the dependent and the independent
      variables was built. The proposed method showed good agreement between the
      experimental data and predictive value, and it has been successfully employed to
      determine metacrate in water samples. The limit of detection was 1 ng mL(-1) and,
      repeatability of the method, described as relative standard deviation, was 5.7%
      (n=5).

PMID- 18721537
TI  - Ionic liquids supported growth of highly ordered microdroplets induced by fluidic
      leakage at poly(dimethylsiloxane) interfaces.
AB  - "Fluidic leakage" caused by vacuum force at the reversible sealing
      poly(dimethylsiloxane) (PDMS) interfaces was converted to one useable avenue,
      which led to formation of highly ordered surfactant microdroplets functionalized
      with ionic liquids (ILs). Vacuum force is the prerequisite to lead constant
      microsolutions to diffuse to the PDMS interfaces. Imidazolium ions of ILs
      rendered structural rearrangement of the surfactant aggregates and the ordered
      droplets formation. The anion tetrafluoroborate of ILs possessed indispensable
      functions in affecting the polarity of the microdroplets and was discovered to
      have enhanced effect on encapsulation of hydrophilic molecules in surfactant
      microdroplets. These interesting phenomena were characterized by various
      analytical methods such as confocal laser scanning microscopy, atomic force
      microscopy, luminescence spectroscopy and UV-vis spectroscopy.

PMID- 18721538
TI  - Sensitive and selective fluorescence determination of trace hydrazine in aqueous
      solution utilizing 5-chlorosalicylaldehyde.
AB  - A facile fluorescent method for the determination of hydrazine in aqueous
      solution with excellent sensitivity was developed. 5-chlorosalicylaldehyde (CS),
      a readily commercially available compound, was applied as the derivatization
      reagent in this work. Under the addition of CS to hydrazine aqueous solution
      (ethanol/water/acetic acid=30/66/4), an intense fluorescence enhancement was
      observed at 570 nm with a large stokes shift of approximately 170 nm. Upon the
      optimal condition, the fluorescence intensity linearly increased with the
      concentration of hydrazine in the range of 0.2 and 9.3 microM with a correlation
      coefficient of R2=0.9995 (n=10) and a detection limit of 0.08 microM. The R.S.D.
      was 2.0% (n=5). Determination of hydrazine in river and drinking water samples
      was successfully performed. Hydrazine vapor sensing by the proposed method was
      also reported.

PMID- 18721539
TI  - Simultaneous determination of two anti-inflammatory drugs in serum using
      isopotential fluorimetry.
AB  - The simultaneous determination of 6-methoxy-2-naphthylacetic acid (6MNA) and
      diflunisal in serum samples using the combination of matrix isopotential
      synchronous fluorescence (MISF) and first derivative technique is proposed. 6MNA
      and diflunisal exhibit overlapped spectra and serum produces background
      fluorescence that precludes the direct determination of these anti-inflammatory
      drugs by conventional fluorimetry. This method provides good analytical results
      for determination of compounds in samples with unknown background fluorescence.
      The method was applied for the simultaneous determination of 6MNA and diflunisal
      in serum samples at concentrations between 20-200 and 100-1000 ng mL(-1),
      respectively, by means of absolute values of first derivative of synchronous scan
      at 247.9/364.0 and 262.6/392.4 nm for 6MNA and diflunisal, respectively. In order
      to obtain maximum sensitivity and adequate selectivity, factors affecting
      fluorescence intensity were studied. As a result, the analyses were performed in
      water at a pH of 7.2, adjusted by using sodium dihydrogen phosphate/hydrogen
      phosphate (0.1M) as a buffer solution. Serum samples were diluted 200 times.
      Analytical parameters of the proposed method were calculated according to the
      error propagation theory. The limit of detection calculated according to Clayton
      was 15.8 and 63.0 ng mL(-1) for 6MNA and diflunisal, respectively. The
      sensitivity, repeatability and reproducibility achieved with the proposed method
      were adequate for the determination of these anti-inflammatory agents in serum
      samples.

PMID- 18721540
TI  - Morphological and chemical optimization of microcantilever surfaces for thyroid
      system biosensing and beyond.
AB  - The development of biosensors is vital in many areas of biotechnology and
      biomedical research. A prominent new class of label-free biosensors are those
      based on ligand-induced nanomechanical responses of microcantilevers (MCs). The
      interaction between biologically significant ligands with bioreceptors (e.g.,
      antibodies or nuclear receptor proteins) immobilized on one side of the MC
      surface causes an apparent surface stress, resulting in static bending of the MC,
      which can be detected by an optical beam bending technique. The three key
      performance metrics of sensitivity, selectivity, and reversibility are foci of
      the work reported herein. The nature of the MC surface and the method by which
      the bioreceptor is immobilized influence these performance metrics and, hence,
      optimization studies involving these were conducted. In our work, the gold
      surface on one side of the MC is first activated via self-assembled monolayer
      formation with amino ethane thiol (AET) then reacted with glutaraldehyde (GA) as
      a crosslinker before finally functionalizing with the protein receptor. We report
      the effect of concentration, reaction time, and pH for these reagents on the
      magnitude of the nanomechanical responses using an anti-immunoglobulin G (anti
      IgG) receptor: IgG ligand test system. By vapor depositing an alloy of silver and
      gold and then etching away the former, a nanostructured "dealloyed" MC surface is
      created that outperforms a smooth gold MC in terms of nanomechanical responses.
      Optimization of the dealloying parameters (thickness, metal ratio) is also
      reported herein using the aforementioned anti-IgG-IgG system. Maximum response
      was obtained with these conditions: 150 nm dealloyed surface, 1 mM aqueous
      solution of AET-incubation time 1h, 1% GA solution in 10mM pH 8 phosphate
      buffered saline (PBS)-incubation time 3h, and 0.5 mg mL(-1) of receptor protein
      solution in 10mM pH 7 PBS-incubation time 1h. Additionally, surprising results
      are reported when Protein A is immobilized first to properly orient the
      bioreceptor IgG molecules. We also report the application of optimum and non
      optimum conditions to detect thyroid disrupting chemicals (TDCs) using MCs
      functionalized with the transport protein thyroxine-binding globulin. Selectivity
      patterns are reported for several TDCs and sensitive detection of thyroxin at sub
      nM levels is demonstrated.

PMID- 18721541
TI  - Macroporous ordered titanium dioxide (TiO2) inverse opal as a new label-free
      immunosensor.
AB  - Photonic crystal sensing materials have been validated that they are very
      sensitive to refractive index changes. Herein, three-dimensionally ordered
      macroporous (3DOM) (>50 nm) TiO2 inverse opal film has been fabricated by the
      self-assembly technique. Based on the TiO2 inverse opal film, the optical
      spectrometer was established for label-free immunosensor. The sensing performance
      of the 3DOM TiO2 was investigated using human IgG/goat anti-human IgG couple,
      which showed that the sensitivity of 3DOM TiO2 inverse opal film could reach to 1
      microg mL(-1) (equivalent to 1.5 pg mm(-2)) of protein concentration detection
      limit. The 3DOM TiO2 inverse opal has a large internal surface area, low
      fluorescence background and unique optical properties. These characteristics
      indicated the feasibility of 3DOM TiO2 inverse opal in label-free immunoassay.

PMID- 18721542
TI  - Pressurized liquid extraction of mate tea leaves.
AB  - The objective of this work is to investigate the influence of process parameters
      on the pressurized liquid extraction (PLE) of Ilex paraguariensis leaves. A
      factorial 2(6-2) experimental design was employed using responses as the
      extraction yield and the chromatographic profile of the extracts. The extraction
      time, polarity of solvent, amount of sample, numbers of PLE cycles, flushing
      volume and extraction temperature were selected as independent variables
      (factors). Results obtained indicated that the solvent polarity was the most
      significant variable in the study, while the amount of sample and extraction
      temperature also showed significant effect. The other variables did not present
      significant influence in the yield of extraction. GC/MS analysis of the extract
      enabled the identification of saturated hydrocarbons, fatty acids, fatty acid
      methyl esters, phytosterols and theobromine in the extracts. Quantitative
      analysis of four compounds presented in the extracts (caffeine, phytol, vitamin E
      and squalene) was performed by the GC/MS in the SIM mode.

PMID- 18721543
TI  - Deoxynivalenol and its conjugates in beer: a critical assessment of data obtained
      by enzyme-linked immunosorbent assay and liquid chromatography coupled to tandem
      mass spectrometry.
AB  - Enzyme-linked immunosorbent assays (ELISAs) are often employed for the control of
      deoxynivalenol (DON) in barley and other intermediates involved in beer
      production chain. Because of the occurrence of high levels of DON-3-glucoside
      (DON-3-Glc) in malt and beer that have been reported for the first time in our
      earlier study, research focused on the accuracy of DON determination by
      immunoassays in cereal-based matrices has been initiated. DON-3-Glc was strongly
      cross-reacting in all examined commercial ELISA test kits (Ridascreen) DON (R
      Biopharm), Veratox 5/5 DON) (Neogen Corporation), Deoxynivalenol EIA (Euro
      Diagnostica), and AgraQuant) DON Assay 0.25/5.0 Test Kit (Romer Labs). The
      highest overestimation in beer analysis, up to 1000%, when taking the DON content
      determined by liquid chromatography coupled to tandem mass spectrometry (LC
      MS/MS) as a reference method, was obtained by AgraQuant assay. Besides of DON-3
      Glc and 3- and 15-acetyldeoxynivalenol (ADONs), also other, not known yet, matrix
      components contributed to false positive results. Similar phenomenon, although in
      a lesser extent due to lower content of these substances, was observed for using
      ELISA in the analysis of wheat. The relationship between a way of sample handling
      and DON overestimation was demonstrated; higher ELISA response was measured in an
      aqueous extract compared to that prepared by acetonitrile-water (84:16, v/v).
      Most of cross-reacting co-extracts were removed by MycoSep# 226 cartridge, what
      leads us to the hypothesis on the presence of currently unknown cross-reactive
      species.

PMID- 18721544
TI  - Effect of hapten structures on specific and sensitive enzyme-linked immunosorbent
      assays for N-methylcarbamate insecticide metolcarb.
AB  - Five different haptens of the N-methylcarbamate insecticide metolcarb were
      designed and synthesized. All of the haptens were conjugated with ovalbumin (OVA)
      for the coating antigen, and one hapten containing all of the structure of
      metolcarb was conjugated with bovine serum albumin (BSA) for the immunogen. Two
      polyclonal antisera were raised against the BSA conjugate, and ten
      antibody/coating conjugate combinations were selected for studies of assay
      sensitivity and specificity for metolcarb. A class-specific combination was
      found, with the I50 of the assay ranged from 0.64 to 20.98 microg mL(-1) for
      seven tested N-methylcarbamate insecticides except for pirimicarb. Considering
      titer, I50 and cross-reactivity of all combinations of antibody/coating
      conjugate, a competitive indirect enzyme-linked immunosorbent assay (ELISA) in a
      homologous system, whose limit of detection (LoD) reached 1.4 ng mL(-1), was
      presented. The results of competitive ELISAs indicated that coating hapten
      structure can significantly affect not only assay sensitivity but also its
      specificity.

PMID- 18721545
TI  - Near infrared spectroscopy: an analytical tool to predict coffee roasting degree.
AB  - The main purpose of this study was to investigate the relationship between some
      coffee roasting variables (weight loss, density and moisture) with near infrared
      (NIR) spectra of original green (i.e. raw) and differently roasted coffee
      samples, in order to test the availability of non-destructive NIR technique to
      predict coffee roasting degree. Separate calibration and validation models, based
      on partial least square (PLS) regression, correlating NIR spectral data of 168
      representatives and suitable green and roasted coffee samples with each roasting
      variable, were developed. Using PLS regression, a prediction of the three
      modelled roasting responses was performed. High accuracy results were obtained,
      whose root mean square errors of the residuals in prediction (RMSEP) ranged from
      0.02 to 1.23%. Obtained data allowed to construct robust and reliable models for
      the prediction of roasting variables of unknown roasted coffee samples,
      considering that measured vs. predicted values showed high correlation
      coefficients (r from 0.92 to 0.98). Results provided by calibration models
      proposed were comparable in terms of accuracy to the conventional analyses,
      revealing a promising feasibility of NIR methodology for on-line or routine
      applications to predict and/or control coffee roasting degree via NIR spectra.

PMID- 18721546
TI  - Study of binding and denaturation dynamics of IgG and anti-IgG using dual color
      fluorescence correlation spectroscopy.
AB  - In this article, we present a systematic study on IgG and Fab fragment of anti
      IgG molecules using fluorescence auto- and cross-correlation spectroscopy to
      investigate their diffusion characteristics, binding kinetics, and the effect of
      small organic molecule, urea on their binding. Through our analysis, we found
      that the diffusion coefficient for IgG and Fab fragment of anti-IgG molecules
      were 37+/-2 microm2s(-1) and 56+/-2 microm2s(-1), respectively. From the binding
      kinetics study, the respective forward (k(a)) and backward (k(d)) reaction rates
      were (5.25+/-0.25)x10(6)M(-1)s(-1) and 0.08+/-0.005 s(-1), respectively and the
      corresponding dissociation binding constant (K(D)) was 15+/-2 nM. We also found
      that urea inhibits the binding of these molecules at 4M concentration due to
      denaturation.

PMID- 18721547
TI  - Hemoglobin recognition of molecularly imprinted hydrogels prepared at different
      pHs.
AB  - The hemoglobin-imprinted hydrogels were fabricated by using N-t-butylacrylamide
      (TBA) acrylamide (AAm) and itaconic acid (IA) monomers and hemoglobin (Hb, MW 65
      kDa) imprinted molecule in pH buffer solutions (pH 4.0, 6.8 and 8.0). The
      nonimprinted hydrogels were also prepared at same conditions without Hb
      imprinting molecule. The effects of pH, initial concentration and adsorption time
      over the Hb adsorption capacity of both imprinted and nonimprinted hydrogels were
      analyzed and found to be strongly dependent on the preparation pH (pH(prep)). The
      maximum Hb adsorption for the imprinted hydrogel prepared at pH 4.0 was found to
      be 12.4 mg protein g(-1) dry gel in pH 4.0 buffer solution. This behavior was
      attributed to the formation of more accessible adsorption sites (imprints)
      because of the non-covalent interactions between the template and network during
      formation in pH 4.0 buffer solution which is below of the isoelectric point (pI
      6.8) of Hb. Langmuir and Freundlich adsorption models were applied to describe
      the equilibrium isotherm. Langmuir analysis showed that an equal class of
      adsorption was formed in the hydrogels. Moreover, batch adsorption equilibrium
      and selectivity studies were also performed by using two reference molecules as
      fibrinogen (Fb, MW 340 kDa) and myoglobin (Mb, MW 17 kDa). The imprinted
      hydrogels have 1.5-2.2 times higher adsorption capacity for Hb than the
      nonimprinted hydrogels prepared at the same pHs, and also have 2.0-3.1 times
      higher selectivity for the imprinted molecule.

PMID- 18721548
TI  - Giant circumflex coronary artery fistula to the superior vena cava in patient
      with multiple valvular disease.

PMID- 18721549
TI  - The rationale for incorporation of HIPAA compliant unique patient, surgeon, and
      hospital identifier fields in the STS database.

PMID- 18721550
TI  - A clash of rights: should smoking tobacco products in public places be legally
      banned?

PMID- 18721551
TI  - Outcomes after repair of the anterior mitral leaflet for degenerative disease.
AB  - BACKGROUND: Repair of anterior mitral disease is challenging. Objectives of this
      study were to (1) compare patients with anterior versus posterior disease, (2)
      identify factors predisposing to replacement rather than repair in anterior
      disease, (3) determine durability of, and survival after, repair, and (4) compare
      outcomes with those after posterior repair. METHODS: From January 1985 to January
      2006, 3,544 patients underwent primary isolated mitral valve surgery for
      degenerative disease, including 307 isolated anterior (252 repairs, 82%) and
      2,754 isolated posterior (2,650 repairs, 96%) leaflet procedures. Logistic
      regression analysis was used to identify predictors of valve replacement and to
      generate propensity scores for risk-adjusted comparisons. Durability was assessed
      by reoperation and return of mitral regurgitation. RESULTS: Patients with
      anterior disease were older and more symptomatic, with more chordal elongation
      and greater changes in cardiac morphology and function; advanced age was
      associated with replacement (p < 0.0001). Unadjusted freedom from reoperation was
      89% at 10 years, worse than after posterior repair (p < 0.0001). Return of 3+ to
      4+ mitral regurgitation was more common in those with anterior than posterior
      repair (11% versus 4% at 1 year; p = 0.03). Unadjusted survival was 83% versus
      88% 10 years after posterior repair, but propensity-adjusted survival was similar
      (p >or= 0.5). CONCLUSIONS: Patients with anterior disease have more symptoms and
      greater changes in cardiac structure and function than do patients with posterior
      disease. Anterior repair is less durable than posterior, but is associated with
      comparable, excellent long-term survival. More durable repair techniques,
      applicable to the broader spectrum of anterior disease, are needed.

PMID- 18721552
TI  - Toward a new paradigm for the reconstruction of posterior leaflet prolapse:
      midterm results of the "respect rather than resect" approach.
AB  - BACKGROUND: The aim of mitral valve reconstruction is restoration of good
      coaptation surface. Resection of the prolapsed area has been the accepted
      technique to repair prolapse of the posterior leaflet (PPL). However, as leaflet
      tissue is the basic component of coaptation surface, the logical corrective
      approach was thought to be the transformation of the posterior leaflet into a
      smooth vertical buttress without resection, the "respect rather than resect"
      approach. METHODS: Between 1994 and 2004, 225 patients underwent a PPL repair for
      severe mitral regurgitation with the respect rather than resect approach, in
      which the prolapse was corrected with artificial chordae. In 193 patients, the
      prolapse was limited to the posterior leaflet; in the remaining 32 patients, both
      leaflets were involved. All patients received ring annuloplasty. Associated
      procedures included myocardial revascularization (21 patients) and tricuspid
      repair (19 patients). Patient demographics were as follows: mean age, 60.7 +/-
      12.9 years; male, 150 (67%); asymptomatic, 102 (45%). RESULTS: Three patients
      died postoperatively (1.3%). Survival at 10 years (88% +/- 6%) was similar to
      expected survival rate (97% +/- 2% for asymptomatic patients and 82% +/- 10% for
      symptomatic patients (p < 0.005)). Ten patients were reoperated on, for a freedom
      from reoperation rate of 93% +/- 3% at 10 years. At echocardiographic follow-up,
      172 patients of 195 (88%) showed mitral regurgitation of 1 or less; and 195 of
      203 patients (96%) were in New York Heart Association functional class I or II.
      CONCLUSIONS: The respect rather than resect approach is safe, effective, and
      durable, and increases technical repair possibilities. Surgical strategy focuses
      on restoration of surface coaptation instead of location and extent of leaflet
      resection.

PMID- 18721553
TI  - The impact of surgical ventricular restoration on mitral valve regurgitation.
AB  - BACKGROUND: Surgical management of functional mitral regurgitation (MR) in
      ischemic cardiomyopathy is controversial. Surgical ventricular restoration (SVR)
      decreases left ventricular volume and may improve MR severity. We assessed the
      impact of SVR on the degree of MR. METHODS: We retrospectively reviewed patients
      with ejection fractions (EF) < 0.35 who underwent SVR with coronary artery bypass
      grafting (SVR+CABG) over a 3-year period. Patients with concomitant mitral valve
      procedures were excluded. Patients with EF < 0.35 who had CABG alone during the
      same time period served as control. Mitral regurgitation was graded 0 to 4+ by
      echocardiogram and ventriculogram. Outcomes included survival, MR grade, and
      cardiac function. RESULTS: Thirty-nine patients received SVR+CABG: 3% (1 of 39)
      had 4+, 10% (4 of 39) had 3+, 51% (20 of 39) had 2+, and 36% (14 of 39) had 0 to
      1+ MR. Thirty-five patients with a similar MR distribution underwent CABG alone.
      Operative mortality was 2.6% for SVR+CABG and 5.7% for CABG patients (p = 0.62).
      At follow-up, MR grade decreased by 57% (2.24 +/- 0.5 to 1.24 +/- 0.9, p < 0.001)
      for the SVR+CABG group compared to 12% (2.25 +/- 0.5 to 2.00 +/- 0.9, p = 0.27)
      for the CABG alone group. SVR+CABG patients had significantly less MR than CABG
      patients at follow-up (1.24 +/- 0.9 vs 2.00 +/- 0.9, p = 0.007), with 15 patients
      improving to 0 to 1+ MR postoperatively versus 6 patients in the CABG cohort (p =
      0.02). Improvement in postoperative EF was significantly greater after SVR+CABG
      (0.13% vs 7%, p = 0.04). Three-year survival was 85% for SVR+CABG and 72% for
      CABG patients (p = 0.39). CONCLUSIONS: SVR+CABG demonstrated greater reduction in
      MR severity at follow-up than CABG alone. Decreased left ventricular volumes and
      improved papillary muscle orientation likely contribute to decreased MR after
      SVR.

PMID- 18721554
TI  - Survival prognosis and surgical management of ischemic mitral regurgitation.
AB  - BACKGROUND: Ischemic mitral regurgitation (IMR) has an adverse prognosis, but
      survival characteristics and management are controversial. This study reviewed a
      20-year series of IMR patients managed with multiple approaches to assess and
      refine surgical strategies. METHODS: Patients having surgery for primary coronary
      disease from 1986 to 2006 were divided into group 1 (no IMR; bypass grafting
      only; n = 16,209), group 2a (IMR; bypass only; n = 3,181), group 2b (IMR; mitral
      repair; n = 416), and group 2c (IMR; mitral replacement; n = 106). Cox
      proportional hazards modeling adjusted for baseline differences, and therapeutic
      adequacy was quantified by area under each survival curve expressed as a
      percentage of group 1. RESULTS: Group 2 patients were older than group 1 patients
      and had worse baseline characteristics. Group 2a had less severe MR and group 2b
      had the most comorbidity. Assuming group 1 provided the best adjusted outcome at
      a given baseline risk, group 2a achieved 97.7%, 2b achieved 93.7%, and 2c
      achieved 79.1% of potential survival (hazard ratio 1.1, 1.4, and 1.6,
      respectively; p < 0.003). Most of the survival difference was perioperative.
      CONCLUSIONS: Worse baseline risk is a major factor reducing long-term survival in
      IMR. Current algorithms in which mild to moderate IMR is managed with bypass only
      (group 2a) generally produced good late results. In patients with moderate and
      severe IMR, repair achieved 93.7% of full survival potential; valve replacement
      was less satisfactory, primarily owing to higher operative mortality. Future
      therapeutic refinement, emphasizing reparative procedures and better
      perioperative care, could enhance the surgical prognosis of IMR.

PMID- 18721555
TI  - Transapical mitral valved stent implantation.
AB  - BACKGROUND: Transcatheter aortic and pulmonary valve replacement is currently
      being tested in human trials. Efforts to create a valved stent to replace the
      atrioventricular valves have shown limited success. This is due to their their
      complex anatomy and function. METHODS: A self-expanding valved stent was created
      for transapical replacement of the atrioventricular valve. Ten pigs underwent
      transapical off-pump mitral valved stent implantation. Data were gathered to
      assess the animals' hemodynamic stability for 60 minutes after implantation. The
      valved stent function was assessed by transesophageal echocardiography (TEE) and
      contrast left ventriculogram. RESULTS: All animals exhibited normal hemodynamics
      immediately after mitral valved stent implantation and maintained stability for
      the entire period of monitoring. Accurate positioning of the valved stent was
      established in all animals. Mild paravalvular regurgitation was found in three
      out of ten animals by TEE and in two animals during left ventriculogram. No left
      ventricular outflow tract obstruction was encountered. CONCLUSIONS: Transapical
      off-pump mitral valved stent implantation is feasible in an acute experimental
      setting. Long-term function of the new valved stent remains to be established.

PMID- 18721556
TI  - The influence of annuloplasty ring geometry on mitral leaflet curvature.
AB  - BACKGROUND: The effect of mitral leaflet curvature on stress reduction is an
      important mechanism in optimizing valve function. We hypothesize that
      annuloplasty ring shape could directly influence leaflet curvature and,
      potentially, repair durability. We describe an echocardiographically based
      methodology for quantifying mitral valve geometry and its application to the
      characterization of ovine mitral valve geometry before and after implantation of
      an annuloplasty ring. METHODS: Multiple mitral annular and leaflet geometric
      variables were calculated for 8 naive adult male sheep using real-time three
      dimensional echocardiographic images. These indexes were recalculated after
      annuloplasty using a 30-mm Carpentier-Edward Physio ring (n = 4; Edwards
      Lifesciences, Irvine, CA) or a 30-mm saddle ring (n = 4). RESULTS: After
      implantation of the Physio ring, the annular height to commissural width ratio
      (AHCWR) decreased from 19.4% +/- 2.3% to 11.1% +/- 2.5% (p = 0.06). After
      implantation of the saddle ring, AHCWR increased from 19.6% +/- 1.3% to 24.3% +/-
      1.3% (p < 0.05). Statistically significant increases in three-dimensional
      Gaussian curvature occurred after implantation within six defined leaflet regions
      (A1 to A3, P1 to P3) of the saddle ring but only within the P1 and P3 leaflet
      regions with the Physio ring. CONCLUSIONS: Annuloplasty ring shape affects
      leaflet curvature. Implantation of a saddle ring reflecting normal human annular
      geometry augmented ovine annular nonplanarity and increased three-dimensional
      leaflet curvature across the entire mitral valve surface. The Physio ring
      decreased annular nonplanarity and increased leaflet curvature only across
      limited regions of the posterior leaflet. These findings confirm the hypothesis
      that ring design influences leaflet curvature.

PMID- 18721557
TI  - Aortic allograft valve reoperation: surgical challenges and patient risks.
AB  - BACKGROUND: Aortic valve allograft reoperation is a challenge for the surgeon and
      a risk to the patient. We examined our experience to identify these challenges
      and risks. METHODS: From April 1987 to January 2006, 130 patients underwent first
      time allograft-related reoperations. Prior implant was subcoronary 32 (25%),
      inclusion-root 28 (22%), and root 70 (53%). Reoperative indications were
      technical failure 11 (8.4%), endocarditis 31 (24%), and structural valve
      deterioration 88 (68%). Reoperative technique was allograft repair 7 (5.4%),
      simple valve replacement 80 (62%), and root replacement 43 (33%). Median follow
      up was 3.1 years. RESULTS: Surgical challenges: 10 adverse intraoperative events
      occurred (7.7%), 3 allograft specific, with rescue from all. Reoperative
      procedure was highly dependent on original implantation technique (31 of 43 root
      replacements after previous roots) and reoperative indication (24 of 43 root
      replacements for endocarditis). Implanted valve prostheses were small for patient
      size, less so in intact native roots (previous subcoronary or inclusion root)
      than retained allografts (Z-value, -1.1 versus -1.6; p = 0.08), but allograft
      root re-replacement allowed normal-sized valves. Patient risks: Relevant
      postoperative morbidities included reoperation for bleeding 7 (5.4%), new
      pacemaker 6 (5.2%), stroke 1 (0.8%), and no myocardial infarction. Hospital
      mortality was 3.8% (5 of 130), 6.5% (2 of 31) for endocarditis. Late patient
      survival was substantially worse for endocarditis than for structural valve
      deterioration (60% versus 90% at 5 years, p = 0.0006). Five-year freedom from
      further reoperation was 94%. CONCLUSIONS: Surgical challenges, even with
      endocarditis, can be surmounted and patient risks minimized by thoughtful
      preparation and appropriate reoperative procedure. An intact native root
      maximizes surgical options.

PMID- 18721558
TI  - Cerebrovascular events after stentless aortic valve replacement during a 9-year
      follow-up period.
AB  - BACKGROUND: One major advantage of biologic aortic valve prostheses is their low
      thrombogenicity compared with mechanical prostheses. The purpose of this study
      was to evaluate the incidence of cerebrovascular events during long-term follow
      up after stentless aortic valve replacement. METHODS: Between 1996 and 2005,
      1,014 patients (mean age, 73 years; range, 20 to 90 years) received stentless
      aortic valve replacement (Freestyle; Medtronic, Minneapolis, MN) and were
      included into the systematic follow-up that was closed in 2006 with a
      completeness of 94.7% and a mean follow-up interval of 3 years (range, 0.5 to 9.8
      years). Predictors for freedom from cerebrovascular events were identified by Cox
      regression. RESULTS: Overall survival was 53% +/- 5% after 8 years (mean, 6.8 +/-
      0.2 years). Permanent atrial fibrillation at time of surgery was a strong
      predictor of impaired survival during follow-up. Freedom from cerebrovascular
      events during follow-up was 68% +/- 5% at 9 years of follow-up. Multivariate
      regression analysis revealed previous stroke, age at implant, diabetes mellitus,
      and carotid lesions as significant risk factors. Especially age older than 75
      years was a strong risk factor for cerebrovascular events during follow-up (p =
      0.004). Atrial fibrillation was not an independent risk factor for
      cerebrovascular events (p = 0.26) but was a strong predictor of poor survival (p
      < 0.001) during follow-up. There was no influence of technique of implantation
      (subcoronary versus full root; p = 0.41), sex (p = 0.35), additional bypass
      grafting (p = 0.65), and the size of the implanted prosthesis (p = 0.47).
      CONCLUSIONS: The risk of cerebrovascular events during follow-up after stentless
      aortic valve replacement is related to the individual risk factors of the
      patients rather than to the valve prosthesis itself. Without additional risk
      factors, patients with these aortic valve prostheses showed an incidence of
      cerebrovascular events similar to those reported for a healthy population
      adjusted for age.

PMID- 18721559
TI  - Analysis of ascending and transverse aortic arch repair in octogenarians.
AB  - BACKGROUND: Increasing numbers of older patients are requiring complex thoracic
      aortic surgery. This retrospective study analyzed early and late outcomes after
      ascending and transverse arch surgery using hypothermic circulatory arrest (HCA).
      METHODS: Between January 1991 and December 2006, 779 patients requiring HCA were
      treated. Outcomes are reported by age group: group 1, 80 years or more (37,
      4.8%); and group 2, less than 80 years (742, 95.2%). Univariate and multivariate
      analyses were used to identify risk factors for morbidity and mortality. RESULTS:
      Early mortality and stroke did not differ between groups. Thirty-day mortality
      was13.5% (5 of 37) in group 1 and 10% (78 of 742) in group 2 (p = 0.57). Stroke
      occurred in 8% (3 of 37) of group 1 patients and 2.7% (20 of 742) of group 2
      patients (p = 0.09). Predictors of stroke were prior stroke (p = 0.003) and pump
      time (p = 0.02). Predictors of early mortality were low glomerular filtration
      rate (p = 0.0001), long cardiopulmonary bypass time (p = 0.0001), and emergent
      repair (p = 0.0009). Retrograde cerebral perfusion was protective against stroke
      (p = 0.0001) and reduced early mortality (p = 0.02). Age was not a predictor of
      stroke (p = 0.12) or early mortality (p = 0.39). Survival in group 1 compared
      with the age-matched US population at 1 year was 56% versus 86% (p = 0.02); at 2
      years, 48% versus 76% (p = 0.03); at 5 years, 36% versus 48% (not significant);
      and at 10 years, 20% versus 20%. CONCLUSIONS: Ascending and aortic arch surgery
      in octogenarians involving profound HCA resulted in reasonable morbidity and
      short- and long-term mortality rates. The use of profound HCA for aortic surgery
      remains warranted in octogenarians.

PMID- 18721560
TI  - Invited commentary. Analysis of ascending aortic aneurysmal disease and complex
      aortic repair in octogenarian patients.

PMID- 18721561
TI  - Curved nitinol stent-graft placement for treating blunt thoracic aortic injury:
      an early experience.
AB  - BACKGROUND: Blunt trauma-induced aortic injury traditionally has been treated
      with early open surgical repair. However, recently endovascular stent-graft
      technology is considered a less-invasive therapeutic alternative, and flexible
      stent-grafts, such as the Matsui-Kitamura stent-graft (MKSG), are being used
      widely. We report our experience with the curved MKSG in treating thoracic aortic
      injuries. METHODS: Nine patients with traumatic thoracic aortic injury underwent
      endovascular surgery (8, emergency; 1, elective) with curved MKSG. The study
      variables were Injury Severity Score, endovascular surgery duration, aortic and
      stent-graft diameter, stay in the intensive care unit, follow-up period, and
      mortality. An MKSG was constructed using the Matsui-Kitamura stent and a
      polyester fabric graft. The stent-graft was placed using the transfemoral
      approach and the wire-tug technique. RESULTS: The mean Injury Severity Score was
      42.3; 5 patients required 6 emergency procedures before the endovascular
      procedure (pneumothorax or hemothorax drainage, 5; transarterial embolization,
      1). In 8 patients (88.9%), we achieved complete pseudoaneurysm exclusion or
      hemostasis in the injured portion. There were no postoperative complications;
      blood loss was minimal, and the intensive care unit stay was 13.4 days. The
      overall hospital mortality was 22.2% (n = 2; causes of death were unrelated to
      MKSG placement). Neither intervention-related mortality during follow-up (mean,
      237.7 days) nor late endovascular graft-related complications (endoleak or graft
      migration) were noted. CONCLUSIONS: Although this study is limited by a small
      sample size and short follow-up period, no collapse or stent-graft fractures were
      noted. Thus, MKSG placement for traumatic thoracic aortic injury appears a safe
      and effective therapy.

PMID- 18721562
TI  - Invited commentary. The ever-elusive optimal treatment of traumatic aortic
      injury.

PMID- 18721563
TI  - Improving results of open arch replacement.
AB  - BACKGROUND: The rapid evolution of endovascular approaches to arch reconstruction
      such as brachiocephalic debranching and endovascular stent grafting renders an
      accurate understanding of contemporary outcomes of conventional open arch surgery
      particularly relevant. METHODS: Cases of arch reconstruction were identified by
      search of the computerized cardiovascular surgical database. Perioperative (30
      day) outcomes as per The Society of Thoracic Surgeons database were evaluated.
      RESULTS: Between January 1, 1993, and June 30, 2007, 347 patients (195 male, 152
      female; median age, 69 years; range, 21 to 88 years) underwent aortic arch
      replacement. Procedures were elective in 232 cases. Total arch replacement was
      performed in 95, including 15 with concomitant replacement of the descending
      thoracic aorta by means of bilateral thoracosternotomy. Modalities adjunctive to
      profound hypothermia and circulatory arrest for cerebral protection have been
      introduced, including retrograde cerebral perfusion and, more recently, selective
      antegrade cerebral perfusion. The overall mortality rate was 8.9% (elective
      procedures, 6.0%) and stroke rate was 8.4% (elective procedures, 6.9%). The
      mortality rate for total arch replacement has declined with adjuncts overall from
      34.6% (9 of 26) with profound hypothermia and circulatory arrest to 21.1% (4 of
      19) with retrograde cerebral perfusion and to 6.0% (3 of 50) with selective
      antegrade cerebral perfusion (p < 0.01), and for elective cases from 30.0% (6 of
      20) with profound hypothermia and circulatory arrest to 14.3% (2 of 14) with
      retrograde cerebral perfusion, and 2.7% (1 of 37) with selective antegrade
      cerebral perfusion (p < 0.01). The corresponding stroke rates were 19.2% (5 of
      26) with profound hypothermia and circulatory arrest, 5.3% (1 of 19) with
      retrograde cerebral perfusion, and 6.0% (3 of 50) with selective antegrade
      cerebral perfusion (p = 0.18) overall and 15.0% (3 of 20) with profound
      hypothermia and circulatory arrest, 7.1% (1 of 14) with retrograde cerebral
      perfusion, and 5.4% (2 of 37) with selective antegrade cerebral perfusion (p =
      0.46) for elective cases. CONCLUSIONS: Currently, open aortic arch replacement
      can be accomplished under elective circumstances with low operative mortality,
      particularly with adjunctive measures for cerebral protection. The results of
      endovascular therapies should be measured against contemporary surgical series.

PMID- 18721564
TI  - Influence of on-pump versus off-pump techniques and completeness of
      revascularization on long-term survival after coronary artery bypass.
AB  - BACKGROUND: Off-pump coronary artery bypass graft surgery (OPCABG) may be
      associated with reduced morbidity and in-hospital mortality. In this study, we
      report the influence of surgery type, number of grafts, and the Index of
      Completeness of Revascularization (ICOR), namely, the number of grafts/number
      diseased vessel systems, on long-term survival. METHODS: From 1997 to 2006,
      12,812 consecutive patients underwent isolated CABG at a single academic center.
      Ten-year survival data were obtained by cross-referencing patients with the
      national Social Security Death Index. A propensity score analysis of 46
      preoperative characteristics balanced risk factors between surgical groups. A
      proportional hazards regression analysis modeled the hazard of death as a
      function of surgery type (on versus off), distal group (1 to 3 versus 4 to 7
      vessels), ICOR, and propensity score. RESULTS: Proportional hazards regression
      analysis showed no significant influence of surgery type or number of grafts on
      long-term survival within the four groups: OPCABG 1 to 3 grafts (n = 3,946; ICOR
      1.11), OPCABG 4 to 7 grafts (n = 1,721; ICOR 1.56), on-pump CABG 1 to 3 grafts (n
      = 3,380; ICOR 1.21), and on-pump CABG 4 to 7 grafts (n = 3,765; ICOR 1.64).
      Irrespective of technique of revascularization, there was a survival advantage
      for patients with higher ICOR. CONCLUSIONS: Long-term survival was similar for
      patients receiving 1 to 3 or 4 to 7 grafts by either on-pump or off-pump
      techniques. However, higher ICOR was associated with improved long- term survival
      within all groups.

PMID- 18721565
TI  - Coronary artery bypass grafting with or without surgical ventricular restoration:
      a comparison.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is an effective treatment for
      ischemic cardiomyopathy. However, patients with ventricular enlargement are known
      to have inferior outcomes. We assessed whether surgical ventricular restoration
      (SVR) with CABG (SVR + CABG) leads to improved outcomes versus CABG alone for
      patients with ischemic cardiomyopathy and ventricular enlargement. METHODS: We
      conducted a case-control study comparing patients with ischemic cardiomyopathy
      and ejection fraction less than 0.35 who underwent SVR + CABG versus CABG alone
      from June 2002 to December 2005. Patients who underwent SVR + CABG were compared
      with control patients who met criteria for SVR + CABG by ventriculogram or
      echocardiogram but received CABG alone. End points included survival,
      rehospitalization for heart failure, and New York Heart Association class.
      RESULTS: During the study period 120 patients underwent SVR + CABG (n = 62)
      versus CABG alone (n = 58). Patients in the SVR + CABG group were younger (60
      versus 64 years; p = 0.04) and more likely to be New York Heart Association class
      III or IV preoperatively (98% versus 86%; p = 0.01). Operative mortality was
      similar between groups (6.4% versus 5.2%; p = 1.00). Ejection fraction was
      similar preoperatively (0.22 versus 0.24; p = 0.31) and postoperatively (0.34
      versus 00.32; p = 0.40). The SVR + CABG patients experienced fewer
      rehospitalizations for heart failure (24% [13 of 54] versus 55% [24 of 44]; p =
      0.006) but had similar 4-year survival (p = 0.60). At follow-up, 80% (50 of 62)
      of SVR + CABG versus 57% (27 of 47) of CABG alone patients improved to New York
      Heart Association class I or II (p = 0.01). CONCLUSIONS: Patients with ischemic
      cardiomyopathy and ventricular enlargement experience similar early survival
      after SVR + CABG or CABG alone. However, SVR + CABG resulted in fewer
      rehospitalizations and better improvements in New York Heart Association class.
      Surgical ventricular restoration with CABG should be offered to eligible patients
      with ischemic cardiomyopathy and ventricular enlargement.

PMID- 18721566
TI  - Is aprotinin safe to use in a cohort at increased risk for thrombotic events:
      results from a randomized, prospective trial in off-pump coronary artery bypass.
AB  - BACKGROUND: Multiple randomized trials have established a favorable safety
      profile for aprotinin use during cardiac surgery, but recent database analyses
      suggest an increased risk of adverse thrombotic events. Our group previously
      demonstrated that off-pump coronary artery bypass (OPCAB) is linked to a
      postoperative hypercoagulable state. In this study, we tested whether aprotinin
      influences thrombotic events after OPCAB. METHODS: Patients randomly received
      saline (n = 61) or aprotinin (2 x 10(6) kallikrein inhibiting units (KIU) loading
      dose, 0.5 x 10(6) KIU/hour [n = 59]) during OPCAB. Aprotinin levels (KIU/mL) were
      analyzed before, and 30 minutes (peak) and 4 hours after the loading dose.
      Estimated glomerular filtration rate (eGFR) was calculated daily based on
      Cockcroft equation with acute kidney injury (AKI) defined as eGFR less than 75%
      of baseline. Major adverse cardiac and cerebrovascular events (MACCE) were
      monitored during the first year, including acute graft failure by predischarge
      computed tomographic angiography. RESULTS: Compared with placebo, the aprotinin
      group developed a significantly lower eGFR on day 3 (p < 0.006), but this
      difference resolved by day 5. Peak aprotinin level correlated with the degree of
      eGFR decline noted on day 3 (r = 0.56, p < 0.03) and independently predicted
      postoperative AKI (odds ratio 8.8, p < 0.008). The receiver operating
      characteristic analysis demonstrated that peak aprotinin level strongly predicts
      AKI (area under the curve = 0.86, 95% confidence interval 0.69 to 1.00). The
      percentage of patients reaching the composite MACCE endpoint was significantly
      reduced in the aprotinin versus placebo group (12 vs 34%, p = 0.01). CONCLUSIONS:
      Compared with placebo, aprotinin use was associated with less MACCE but more AKI
      after OPCAB. The strong relationship between the peak aprotinin level and
      subsequent AKI suggests weight-based protocols for dosing aprotinin may reduce
      this risk.

PMID- 18721568
TI  - Invited commentary. The hemodynamic effects of intra-aortic balloon
      counterpulsation (IABC) on graft flow in coronary artery surgery.

PMID- 18721567
TI  - Effects of intra-aortic balloon pumping on graft flow in coronary surgery: an
      intraoperative transit-time flowmetric study.
AB  - BACKGROUND: We investigated hemodynamic effects of intra-aortic balloon pumping
      (IABP) in in-situ and aorta-coronary (A-C) grafts during coronary artery bypass
      grafting (CABG). METHODS: One hundred seventy-two grafts, including 84 in-situ
      left internal thoracic arteries (LITAs), were examined intraoperatively with a
      transit-time flowmeter in 84 patients who had prophylactic IABP. The following
      measurements were obtained for each graft during off-IABP and on-IABP: mean flow,
      maximal flow, pulsatility index, and diastolic filling index. Coronary angiograms
      were performed 14 +/- 5 days after coronary artery bypass graft surgery to verify
      the patency of the grafts. RESULTS: All measurements of 163 patent and measurable
      grafts were significantly increased with IABP: mean flow 46 +/- 27 to 51 +/- 29
      mL/min; maximal flow 87 +/- 52 to 121 +/- 69 mL/min; pulsatility index 2.2 +/-
      1.4 to 3.1 +/- 1.4; and diastolic filling index 64% +/- 8% to 71% +/- 9% (p <
      0.001). Among them, the degrees of increase of mean flow and diastolic filling
      index were significantly different between the in-situ LITAs and A-C grafts (mean
      flow 18% +/- 20% versus 10% +/- 15%, p = 0.04; diastolic filling index 10% +/- 8%
      versus 14% +/- 9%, p = 0.04). CONCLUSIONS: IABP assist significantly increases
      graft flow and also diastolic components of flow. The degree of increase is
      greater in the in-situ LITA supplying the left anterior descending artery than in
      A-C grafts anastomosed to other coronary arteries. IABP increases the diastolic
      component more in A-C grafts than in in-situ LITAs, probably because of different
      flow characteristics of the two grafts.

PMID- 18721569
TI  - Radial artery harvesting for coronary artery bypass grafting: a stepwise-made
      decision.
AB  - BACKGROUND: The purpose of this study was to propose a safe, stepwise, testing
      system to select radial arteries that are suitable for conduits on the basis of
      their morphologies and characteristics of the collateral circulation. METHODS:
      Before operation, 113 patients underwent the modified Allen test, Doppler
      ultrasonography, and pulse oximetry testing. Morphologic criteria used for radial
      artery exclusion were small size of radial or ulnar artery (< 2 mm in inner
      diameter), diffuse calcifications, and congenital anomalies of forearm arteries.
      Collateral circulation was interpreted as insufficient if the reverse flow in the
      anatomic snuffbox was absent or if the increase of the ulnar peak systolic flow
      velocity was less than 20%. RESULTS: A positive modified Allen test was found in
      10.6% of patients. As assessed by Doppler ultrasonography, 27 patients (23.9%)
      were not candidates for radial artery harvesting according to morphologic and
      functional abnormalities of forearm and hand circulation. Pulse oximetry test
      results were abnormal in 6.2%. After a follow-up period of 8.9 +/- 1.8 months, 23
      patients (29.1% of operated patients) were controlled for Doppler
      ultrasonographic changes in the ulnar artery. The mean peak systolic flow
      velocity was significantly higher than the preoperative value measured at rest (p
      < 0 .001). CONCLUSIONS: After preoperative tests, including the modified Allen
      test, Doppler ultrasonography, and pulse oximetry, 30.1% of patients were not
      considered candidates for radial artery harvesting. This method provides
      preoperative radial artery selection according to its morphologies, compensatory
      capacity of collateral circulation, and anatomic properties of ulnar artery.

PMID- 18721570
TI  - Right heart dysfunction after left ventricular assist device implantation: a
      comparison of the pulsatile HeartMate I and axial-flow HeartMate II devices.
AB  - BACKGROUND: Right heart dysfunction confers significant morbidity and mortality
      after left ventricular assist device implantation and historically occurs in as
      many as a third of patients. It is unknown whether newer axial flow pumps have a
      different impact on postimplant right heart dysfunction. We compared the
      incidence of right heart dysfunction after implantation of the pulsatile
      HeartMate I (XVE) and the continuous flow HeartMate II left ventricular assist
      device. METHODS: We retrospectively reviewed patients who underwent HeartMate I
      or HeartMate II implantation between June 2000 and March 2007. Right heart
      dysfunction was defined as inotropic/vasodilator support for 14 or more
      consecutive days or the need for a right ventricular assist device, or both.
      RESULTS: Seventy-seven patients underwent HeartMate implantation; 43 received a
      HeartMate I and 34 received a HeartMate II, for a mean left ventricular assist
      device support time of 202 and 160 days, respectively. Operative mortality was
      lower for HeartMate II patients (28% versus 15%; p = 0.26). The HeartMate II
      patients had lower preoperative right ventricular stroke work index. Pulmonary
      vascular resistance index, right ventricular stroke work index, and pulmonary and
      right atrial pressures improved and were similar between groups postoperatively.
      Overall, right heart dysfunction developed in 35% of HeartMate I patients (15 of
      43) and 41% of HeartMate II patients (14 of 34; p = 0.63). Fewer HeartMate II
      patients (2) than HeartMate I patients (5) required 7 or more days of
      epinephrine, whereas more HeartMate II patients (7) than HeartMate I patients (5)
      required 7 or more days of milrinone. Six HeartMate I and 3 HeartMate II patients
      required right ventricular assist device implantation for right heart failure.
      Survival was similar (p = 0.7) between groups at, respectively, 3 (63% versus
      62%), 6 (58% versus 58%), and 12 months (49% versus 48%). CONCLUSIONS: Right
      heart dysfunction is a persistent clinical problem after left ventricular assist
      device placement. We report the first study comparing the incidence of right
      heart dysfunction after HeartMate I versus HeartMate II implantation. Although
      the incidence of right heart dysfunction was similar, fewer HeartMate II patients
      required right ventricular assist device placement and fewer required pure
      inotropic support for right heart failure.

PMID- 18721571
TI  - The apolipoprotein E epsilon4 allele is not associated with cognitive dysfunction
      in cardiac surgery.
AB  - BACKGROUND: The plasma protein apolipoprotein E (APOE) is a risk factor for
      degenerative cognitive decline manifested by mild cognitive impairment and later
      by Alzheimer's disease. Patients undergoing coronary artery bypass grafting
      (CABG) are known to have a high prevalence of preexisting cognitive impairment
      and postoperative cognitive dysfunction. Because both mild cognitive impairment
      and Alzheimer's disease generally occur in elderly individuals, the age group
      that commonly present for CABG, we investigated if the APOE epsilon4 allele was
      associated with patients manifesting preexisting cognitive impairment and
      postoperative cognitive dysfunction. METHODS: The DNA of 282 patients who had
      undergone neuropsychologic testing before and 3 and 12 months after CABG was
      analyzed for APOE genotype. Patients were classified as having preexisting
      cognitive impairment if cognitive function was decreased in two or more tests
      compared with a healthy control group. Postoperative cognitive dysfunction was
      defined as a decrease in two or more tests compared with the group mean baseline
      score. RESULTS: The APOE epsilon4 allele was found in 83 (29.4%) patients.
      Although preexisting cognitive impairment was present in 105 (37.2%) and
      postoperative cognitive dysfunction in 33 (12%) and 31 (11%) at 3 and 12 months
      postoperatively, there was no relationship with the presence of the APOE epsilon4
      allele or any of the six genotypes. CONCLUSIONS: Preexisting cognitive impairment
      and postoperative cognitive dysfunction are not associated with APOE epsilon4
      genotype, suggesting that cognitive impairment both before and after CABG may not
      be associated with degenerative cognitive decline.

PMID- 18721572
TI  - Invited commentary. The apolipoprotein E epsilon4 allele.

PMID- 18721573
TI  - Epicardial pulmonary vein isolation: a long-term histologic and imaging animal
      study comparing cryothermy versus radiofrequency.
AB  - BACKGROUND: Simplifications of the Cox-Maze procedure to treat atrial
      fibrillation (AF) include epicardial pulmonary vein (PV) isolation using various
      sources to create lines of conduction block. The creation of transmural lesions
      has been a concern. The heat-sink effect caused by blood flow has limited the
      effectiveness of unipolar radiofrequency and linear application of cryothermy,
      which should be abolished when clamp devices are used for PV isolation. The
      efficacy and safety of epicardial beating-heart PV isolation with clamp devices
      using cryothermy or bipolar radiofrequency energy was studied. METHODS: Twelve
      domestic pigs underwent beating-heart epicardial PV isolation using cryothermy (n
      = 6) or radiofrequency (n = 6) energy. Follow-up was 30 days for 3 animals of
      each group and 90 days for the others. Lesions were assessed by epicardial
      pacing, cardiac magnetic resonance imaging (MRI), and histologic analysis.
      RESULTS: Immediate and long-term electrical isolation of PVs was achieved with
      both energy sources. Histologic analysis showed transmural lesions in all animals
      at 30 and 90 days. Cardiac MRI showed no evidence of PV stenosis or thrombus
      formation. Mean left atrial ejection fraction was 0.36 +/- 0.01, 0.36 +/- 0.02,
      and 0.36 +/- 0.01 at baseline and at 30 and 90 days, respectively (p = 0.360 and
      0.230, respectively) and not significantly different with cryothermy or
      radiofrequency ablations. CONCLUSIONS: Beating-heart PV isolation using
      epicardial cryothermy or radiofrequency ablation produces transmural lesions with
      complete electrical conduction block, with low or no risk of endocardial
      thrombosis or PV stenosis. This approach may be useful for PVI in selected
      patients with AF caused by PV triggers.

PMID- 18721574
TI  - Arrhythmia surgery in patients with and without congenital heart disease.
AB  - BACKGROUND: Arrhythmia surgery has favorably impacted the clinical course of
      debilitating atrial and ventricular arrhythmias in patients with and without
      congenital heart disease. This study reviews arrhythmia mechanisms and documents
      long-term outcome of patients undergoing arrhythmia operations alone or
      associated with congenital heart repairs. The analysis excludes Fontan conversion
      patients. METHODS: Between 1987 and 2007, arrhythmia operations were done in 11
      patients without associated congenital heart disease and in 89 along with
      congenital heart repairs. Mean age was 15.9 +/- 12.5 years (range, 7 days-48
      years); 7 were infants (mean age, 23 +/- 16 days). Resternotomy was performed in
      65 (65%). Two functional ventricles were present in 67 patients; 33 had 1
      functional ventricle. Arrhythmias included macro-reentrant atrial tachycardia in
      45, atrial fibrillation in 11, accessory connections in 19, atrioventricular
      nodal reentry tachycardia in 6, focal atrial tachycardia in 6, and ventricular
      tachycardia in 13. RESULTS: Operative mortality was 3 (3.0%) due to advanced
      associated congenital heart disease. There were 4 late deaths (4.0%) and 2 late
      cardiac transplants (2.0%). Freedom from arrhythmia recurrence at 1 and 10 years
      was 94% and 85% for atrial arrhythmias, and 85% and 68% for ventricular
      arrhythmias, respectively. CONCLUSIONS: Successful surgical therapy for atrial
      arrhythmias can be performed safely with a high freedom from recurrence rate in
      patients with and without associated congenital heart disease. Surgical ablation
      for ventricular arrhythmias is less predictive. Complexity of the underlying
      congenital heart disease and hemodynamic status may contribute to potential
      arrhythmia recurrence or new onset arrhythmia manifestation.

PMID- 18721575
TI  - Ventricular function deteriorates with recurrent coarctation in hypoplastic left
      heart syndrome.
AB  - BACKGROUND: Recurrent coarctation (re-CoA) after stage I palliation in
      hypoplastic left heart syndrome (HLHS) is deleterious. We studied whether re-CoA
      had an effect on ventricular systolic function. METHODS: Retrospectively reviewed
      were HLHS patients surviving stage I Norwood palliation (stage I) and
      cavopulmonary shunt (CPS) between January 2004 and February 2007.
      Echocardiographic right ventricular fractional area change (RV-FAC) was used to
      evaluate ventricular systolic function after stage I, before CPS, and before
      Fontan procedures. Cardiac catheterization and magnetic resonance imaging data
      before CPS were reviewed to assess re-CoA, using a coarctation index (CI =
      isthmus diameter/descending aortic diameter). RESULTS: Fifty-one patients were
      included, and 21 had a CI of less than 0.75 (mean, 0.82 +/- 0.19; 21). Twelve
      patients required arch balloon dilation between CPS and Fontan. The change of RV
      FAC for all patients between stage I and CPS was -2.2% +/- 9.6%. Pearson
      correlation coefficient demonstrated a significant correlation between lower CI
      values and lower RV-FAC at the pre-CPS echocardiogram (r = .35, p = 0.03); and
      lower CI values and greater decrease in RV-FAC between stage I and pre-CPS
      evaluation (r = 0.40, p = 0.018). At follow-up pre-Fontan, RV-FAC for patients
      who underwent balloon dilation for re-CoA recovered to a level that was inferior
      but not significantly different from that of patients who did not need balloon
      dilation. CONCLUSIONS: Recurrent aortic arch obstruction after stage I for HLHS
      is associated with worse RV systolic function at the time of stage II operation.
      Timely intervention on the re-CoA results in recovery of RV function.

PMID- 18721576
TI  - Impact of multiplanar review of three-dimensional echocardiographic data on
      management of congenital heart disease.
AB  - BACKGROUND: In patients with congenital cardiac malformations, accurate diagnosis
      is critical in diagnosis and management. The multiplanar review mode (MPR) allows
      the operator to cut three-dimensional (3D) echocardiographic data sets in
      infinite planes, and to review the moving image in three simultaneous orthogonal
      planes. We sought to describe the clinical utility of MPR of 3D echocardiography
      for analysis of congenitally malformed hearts. METHODS: Cross-sectional and 3D
      MPR echocardiography was performed in 300 patients with congenitally malformed
      hearts. RESULTS: Analysis in multiplanar mode was possible in all patients. New,
      clinically important information, which altered management or changed the
      principal diagnosis, was obtained in 32 (11%) cases. This determined suitability
      for biventricular repair in 11 patients, clarified the morphology of
      atrioventricular valves in 7, helped in assessment of aortic, mitral, or
      prosthetic valvar disease in 13, and identified a vascular ring in the other
      patient. CONCLUSIONS: 3D MPR is feasible in the setting of the congenitally
      malformed heart, permitting focused and in-depth analysis. This substantially
      improves the understanding of functional morphology, above the information
      derived from cross-sectional echocardiography. We recommend the use of the 3D
      format with MPR for patients with complex congenital cardiac disease.

PMID- 18721577
TI  - Nitric oxide and milrinone: combined effect on pulmonary circulation after Fontan
      type procedure: a prospective, randomized study.
AB  - BACKGROUND: Early morbidity and mortality after Fontan operations are related to
      the elevation of postoperative pulmonary vascular resistance. Inhalation of
      nitric oxide (iNO) and intravenous milrinone are two options capable of reducing
      pulmonary vascular resistance. We hypothesized that their combined use could
      maximally stabilize the pulmonary circulation after Fontan operation. METHODS:
      Forty-six patients with high pulmonary vascular resistance (transpulmonary
      pressure gradient >10 mm Hg or central venous pressure >15 mm Hg) and impaired
      oxygenation after Fontan operation were prospectively randomized into three
      groups: group Mil (n = 15, milrinone at 0.5 microg x kg(-1) x min(-1)), group iNO
      (n = 15, iNO at <20 ppm), and group iNO + Mil (n = 16, iNO plus Mil). Pulmonary
      hemodynamic and oxygenation changes were compared among the three groups.
      RESULTS: Inhalation of nitric oxide with milrinone led to (1) the most
      significant reduction of pulmonary vascular resistance (transpulmonary pressure
      gradient from 11.26 +/- 1.40 mm Hg [baseline] to 7.93 +/- 0.90 mm Hg [24-hour
      use] in group iNO + Mil versus from 11.10 +/- 1.38 to 8.69 +/- 0.86 mm Hg; p =
      0.048 in group iNO and from 11.17 +/- 1.41 mm Hg to 9.72 +/- 1.32 mm Hg; p <
      0.001 in group Mil); (2) the most significant improvement of arterial blood
      oxygenation (ratio of arterial oxygen partial pressure to inspired fraction of
      oxygen from 68.88 +/- 14.09 to 131.25 +/- 15.92 in group iNO + Mil versus from
      70.07 +/-14.24 to 120.20 +/- 15.92; p = 0.047 in group iNO and from 72.60 +/-
      12.92 to 95.20 +/- 13.49; p < 0.001 in group Mil). Time on mechanical ventilation
      was shortest in group iNO + Mil (p = 0.043). CONCLUSIONS: Combined use of iNO and
      milrinone optimally stabilized pulmonary hemodynamics after Fontan operation.

PMID- 18721578
TI  - The relationship between hospital surgical case volumes and mortality rates in
      pediatric cardiac surgery: a national sample, 1988-2005.
AB  - BACKGROUND: Overall surgical volumes and raw mortality rates are frequently used
      to compare pediatric cardiac surgical programs, but unadjusted comparisons are
      potentially unreliable. We sought to quantify the relationship between hospital
      volume and pediatric cardiac surgical mortality. METHODS: Pediatric cardiac
      operations assigned to Risk Adjustment for Congenital Heart Surgery, version 1
      (RACHS-1) categories were retrospectively identified by International
      Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) coding
      from the Nationwide Inpatient Sample, 1988-2005. Hospitals were grouped by yearly
      pediatric cardiac surgical volume (very small, <or= 20; small, 21 to 100; medium,
      101 to 200; large, > 200). Mortality rates were adjusted for surgical volume,
      case mix (RACHS-1 categories), patient age, and year of operation by logistic
      regression. RESULTS: We identified 55,164 operations from 307 hospitals; 188
      (61%) performed 20 or fewer cases per year. The unadjusted mortality rate at very
      small hospitals was no different than at large hospitals (odds ratio, 1.0, 95%
      confidence interval [CI] 0.7 to 1.4). After adjustment for RACHS-1 category and
      age, large hospitals performed significantly better than all other volume groups.
      As a discriminator of mortality, volume performed significantly worse than a
      model with RACHS-1 category and age (receiver operating characteristic [ROC]
      curve area, 0.60 vs 0.81). CONCLUSIONS: As a discriminator of mortality, volume
      alone was only marginally better than a coin flip (ROC curve area of 0.50).
      However, large-volume hospitals performed more complex operations and achieved
      superior results; therefore, the use of overall, unadjusted mortality rates to
      evaluate institution quality is misleading. Hospital comparisons and pay-for
      performance initiatives must be based on robust risk-adjusted comparisons.

PMID- 18721579
TI  - Repeat sternotomy in congenital heart surgery: no longer a risk factor.
AB  - BACKGROUND: The risk of repeat sternotomy (RS) is often taken into account when
      making clinical management decisions. Current literature on RS suggests a risk of
      approximately 5% to 10% for major morbidity. We sought to establish the true risk
      of RS in a contemporary pediatric series. METHODS: All RS between October 2002
      and August 2006 were analyzed (602 RS in 558 patients). Median age was 3.6 years
      (range, 0.1 to 45.1); weight, 14.2 kg (2.0 to 112.2). Operations performed at RS
      were Glenn 22% (131), Fontan 21% (129), aortic valve repair/replacement 12% (72),
      right ventricle-pulmonary artery conduit 11% (67), Rastelli 7% (39), heart
      transplant 5% (31), and other 22% (133). Forty-seven percent of patients (280)
      had single-ventricle physiology. Incidence of second sternotomy was 67% (406),
      third 28% (166), fourth 4% (24), fifth 0.8% (5), and sixth 0.2% (1). A major
      injury upon RS was defined as one causing hemodynamic instability requiring
      vasopressor support or emergent transfusion; femoral cannulation or emergent
      cardiopulmonary bypass; and any morbidity. A minor injury is any other injury
      during RS. RESULTS: The incidence of a major injury was not different between RS
      (0.3%; 2 of 602) and first-time sternotomy (0%; 0 of 1,274; p > 0.1). Incidence
      of a minor injury was 0.66% (4 of 602). No injury resulted in hemodynamic
      instability, neurologic injury, or death. Two patients (0.3%) required a
      nonemergent blood transfusion secondary to injury. (Nonemergent was defined as
      adminstration rate of less than 0.2 cc/kg/min and less than 10 cc/kg in total.)
      Femoral cannulation was performed in 4 of 602 RS cases (< 0.6%). Sternal wound
      infection was 0.5% (3 of 602); reoperation for postoperative bleeding was 1% (8
      of 602). Median intensive care unit stay was 3 days (1 to 174); median hospital
      stay was 7 days (1 to 202). Hospital survival was 98%. CONCLUSIONS: Repeat
      sternotomy can represent a negligible risk of injury and of subsequent morbidity
      or mortality. Therefore, the choice of management strategies for patients should
      not be affected by the need for RS.

PMID- 18721581
TI  - Invited commentary. The role of tri-modality therapy in stage III nonsmall cell
      lung cancer (NSCLC) is highly controversial.

PMID- 18721580
TI  - Phase I/II trial of hyperfractionated radiation and chemotherapy followed by
      surgery in stage III lung cancer.
AB  - BACKGROUND: We have previously demonstrated that high-dose chemoradiotherapy
      followed by resection for patients selected on the basis of mediastinal
      sterilization was feasible and resulted in excellent outcomes. This study was
      designed to determine the ability to intensify our prior approach utilizing
      hyperfractionated radiation and more aggressive consolidative chemotherapy.
      METHODS: Patients with documented stage IIIA/B nonsmall-cell lung cancer,
      performance status 0 to 2, and adequate organ function were eligible. A phase I
      portion utilized escalating doses of carboplatin and vinorelbine, commencing with
      areas under the curve of 1 and 5 mg/m(2), respectively, and concurrent 69.6 Gy
      hyperfractionated radiotherapy. A phase II portion utilized the identical
      radiotherapy with carboplatin/vinorelbine at the maximum tolerated dose
      established in phase I. Patients for whom mediastinal nodal clearance was
      demonstrated underwent resection. All patients were to receive consolidation
      chemotherapy consisting of carboplatin/vinorelbine for three cycles, followed by
      docetaxel for three cycles. Prophylactic cranial irradiation was offered to
      patients after completion of therapy. RESULTS: Forty-seven patients participated
      in the study (33 IIIA, 14 IIIB; 15 men, 32 women; median age, 56 years). The
      maximum tolerated dose for concurrent carboplatin/vinorelbine and
      hyperfractionated radiotherapy was established at areas under the curve of 1 and
      10 mg/m(2), respectively. Twenty-eight patients completed trimodality treatment
      including surgery. Median survival time for the entire study cohort (n = 47) is
      29.6 months, and it is 55.8 months for patients with mediastinal clearance who
      underwent resection (n = 28). CONCLUSIONS: Surgical resection of locally advanced
      stage IIIA and IIIB nonsmall-cell lung cancer after induction hyperfractionated
      radiation and concurrent chemotherapy is safe and well tolerated. Whether this
      approach is superior to less aggressive therapy is uncertain and will require
      comparative studies.

PMID- 18721582
TI  - The treatment of patients with stage IIIA non-small cell lung cancer from N2
      disease: who returns to the surgical arena and who survives.
AB  - BACKGROUND: Stage IIIA non-small cell lung (NSCLC) from N2 disease is common, but
      represents a heterogeneous group of patients. Predictors of who completes their
      neoadjuvant chemoradiotherapy and undergoes subsequent surgical resection are
      unknown. METHODS: This retrospective cohort study used a prospective database.
      Patients who had biopsy-proven, nonbulky N2 disease underwent neoadjuvant
      chemoradiotherapy and were restaged or resected, or both. RESULTS: There were 402
      patients, and 326 (81%) completed their neoadjuvant therapy. Only 198 (50%)
      returned for definitive pathologic restaging, and 149 (37%) underwent thoracotomy
      for attempted resection. Predictors of who returned to the surgical arena were
      age (< 70), multiple node involvement, and response to neoadjuvant therapy. The 5
      year survival was 8% for the 253 patients who did not return for restaging but
      was 47% for the 149 patients who underwent thoracotomy (p < 0.001). The 5-year
      survival for selected subgroups of patients who underwent complete resection was
      42% for the 14 patients who had unsuspected recalcitrant N2 disease, 49% for the
      65 patients who had a partial response, and 53% for the 34 patients who had a
      complete response. CONCLUSIONS: Only 37% of patients with favorable, nonbulky,
      biopsy-proven N2 disease actually complete their neoadjuvant therapy, undergo
      restaging, and then return for attempted resection. Only 28% undergo complete
      resection. However, in this highly selected subset of patients, the 5-year
      survival is 47% or better if partial or complete pathologic response is achieved.
      Therefore, surgical resection remains a viable treatment for selected patients
      with favorable N2 NSCLC.

PMID- 18721583
TI  - Multiple lung cancers prognosis: what about histology?
AB  - BACKGROUND: Among multiple lung cancers (MLC), some may have similar histologic
      classification. Demonstrating that the second tumor is a metastasis would change
      the stage and consequently the management. Our purpose was to reconsider this
      consequence. METHODS: We reviewed 234 patients (194 male and 40 female, from 37
      to 83 years of age) with synchronous and metachronous non-small cell MLC. Surgery
      consisted of a potentially curative complete resection with lymphadenectomy.
      Patients with similar histologic MLC (considered as metastasis) were compared
      with those with different histologic classification in terms of MLC chronology,
      type of resection, pT and pN, stage, and overall survival. RESULTS: There were
      116 metachronous (ipsilateral, n = 48; contralateral, n = 68) and 118 synchronous
      MLCs (bilateral, n = 10; same lobe, n = 57; other lobe, n = 51). Pneumonectomy
      was performed in 77 patients, lobectomy in 103, and lesser resection in 54.
      Histologic classification was similar in 57.9% of patients and different in
      42.1%. The 5-year survival rates tended to be lower in patients with synchronous
      MLCs (23.4% versus 31.6%; p = 0.07). They were higher when synchronous MLCs were
      located in the same lobe than if they were located in another lobe (29.9% versus
      15.6%; p = 0.022). Whatever the type of MLC, the 5-year survival rates were not
      correlated with similar or different histologic classification. CONCLUSIONS: Our
      analysis supports that surgery is safe and warranted in MLC patients even if
      synchronous MLCs present ominously. Changing the staging by establishing the
      diagnosis of metastasis is probably an important issue warranting further
      biologic research, but according to our results this diagnosis must not in any
      case preclude surgery.

PMID- 18721584
TI  - Patient-centered quality indicators for pulmonary resection.
AB  - BACKGROUND: Quality of care is increasingly scrutinized. However, no standard
      quality measures exist for surgical care of patients undergoing pulmonary
      resection. METHODS: Our thoracic surgical team developed a set of patient
      centered quality of care measures specific to patients undergoing pulmonary
      resection. Measures were chosen that demonstrated evidence-based preoperative
      assessment, adequate mediastinal staging, and interventions to prevent and
      expeditiously treat postoperative morbidity. Medical records of all patients
      undergoing pulmonary resection in 2005 were analyzed. RESULTS: In all, 606
      patients (men:women = 330:276) underwent 628 pulmonary resections. Median age was
      65.8 years (range, 2 to 93). Operative mortality was 2.1%. Pulmonary function
      testing within 1 year before surgery was documented in 74.2%. Electrocardiogram
      within 90 days before surgery was documented in 81.6% of patients 50 years and
      older. Smoking history was documented in all patients, and smoking cessation
      consultation was offered to 85.7% of current smokers. Deep venous thrombosis
      prophylaxis was implemented in 99.7%. Mediastinal staging was documented in 94.0%
      of patients undergoing lung cancer resection (n = 333). Postoperatively, 92.4% of
      patients used incentive spirometry. Atrial fibrillation treatment occurred within
      45 minutes of onset in 70.5%. Postoperative analog pain scores were above 6 in
      only 7.4% of assessments; treatment and reassessment occurred within 2 hours in
      81.0%. Follow-up planning was documented at hospital discharge in 100%. No
      National Quality Forum "never events" occurred. CONCLUSIONS: Patient-centered and
      clinically relevant quality measures can be developed and evaluated in general
      thoracic surgery. This panel of quality indicators highlights and guide areas for
      potential improvement in the care of patients undergoing pulmonary resection.

PMID- 18721585
TI  - Invited commentary. Two reactions from thoracic surgery.

PMID- 18721586
TI  - Radiotracer-guided thoracoscopic resection is a cost-effective technique for the
      evaluation of subcentimeter pulmonary nodules.
AB  - BACKGROUND: Excisional biopsy of small subcentimeter pulmonary nodules can be
      difficult using standard thoracoscopic techniques and may require thoracotomy.
      Radiotracer-guided thoracoscopic resection (RGTR) was developed to facilitate
      resection of intraparenchymal subcentimeter pulmonary nodules. Decision analysis,
      used to model cost and effectiveness, is useful to compare treatment options. We
      hypothesize that RGTR strategy is more cost-effective compared with thoracotomy
      for subcentimeter pulmonary nodules. METHODS: The cost-effectiveness of RGTR
      versus thoracotomy for evaluating highly suspicious subcentimeter pulmonary
      nodules was examined with a decision analysis model (Fig 1). A 40-patient
      institutional cohort who underwent RGTR was used to estimate probabilities and
      costs of the two treatment options within the model. Effectiveness was estimated
      using 5-year, stage-specific cancer survival and population survival curves. The
      Society of Thoracic Surgeons General Thoracic Database was queried obtaining
      mortality estimates for thoracotomy and thoracoscopic wedge resections. These
      were used to adjust the 5-year survival estimates of patients with benign
      disease. Sensitivity analyses determined model robustness and the thresholds at
      which the most cost-effective strategy changed. RESULTS: Radiotracer-guided
      thoracoscopic resection was 95% successful with no mortality. The average cost-to
      effectiveness ratio of RGTR strategy was $27,887 versus $32,271 for thoracotomy.
      Sensitivity analyses demonstrated that the thoracotomy strategy was more cost
      effective if the estimated cost of RGTR increased by 33% or the estimated cost
      effectiveness of thoracotomy decreased by 14% or more. Radiotracer-guided
      thoracoscopic resection was more cost-effective as long as the probability of
      success was greater than 44%. CONCLUSIONS: Decision analysis is a useful tool to
      evaluate treatment options for thoracic surgeons, and RGTR is a more cost
      effective strategy than thoracotomy for subcentimeter pulmonary nodules.

PMID- 18721587
TI  - Postthymectomy myasthenia gravis: relationship with thymoma and antiacetylcholine
      receptor antibody.
AB  - BACKGROUND: Myasthenia gravis occasionally develops in a postthymectomy patient
      with no preoperative history of this disease. METHODS: We retrospectively
      assessed the clinical course, history, and findings of myasthenia gravis, and
      examined the serum titers of antiacetylcholine receptor-binding antibody in
      patients who had undergone thymectomy. RESULTS: We enrolled 67 patients with
      thymoma and 11 with other thymic tumors, all of whom underwent thymectomy. Twelve
      thymoma patients had had myasthenia gravis preoperatively, and their serum titers
      were all positive for antiacetylcholine receptor-binding antibody. Thirteen of 55
      patients (24%) who had had no preoperative myasthenia gravis, but none with other
      thymic tumors (p < 0.0001), had a similar positive reaction. Five of the 55
      thymoma patients without preoperative myasthenia gravis presented with the
      disease 3 to 46 months after thymectomy. These 5 patients showed no significant
      clinical or pathologic features, and in only 1 did the tumor recur. However, they
      all, including 2 patients who had shown negative antiacetylcholine receptor
      binding antibody titers preoperatively, showed the presence of antiacetylcholine
      receptor antibody after onset. No postoperative elevation of the
      antiacetylcholine receptor binding antibody titer was observed in any
      postthymectomy patient who had no myasthenia gravis. CONCLUSIONS: We found that
      patients in whom postthymectomy myasthenia gravis developed showed high titers of
      antiacetylcholine receptor-binding antibody at the onset of the myasthenia
      gravis. We suggest that a positive preoperative antiacetylcholine receptor
      antibody level may be a risk factor for postthymectomy myasthenia gravis.

PMID- 18721588
TI  - Mediastinal paragangliomas: the mayo clinic experience.
AB  - BACKGROUND: Extra-adrenal catecholamine-secreting tumors are referred to as
      paragangliomas. We reviewed our experience with mediastinal paragangliomas
      treated at Mayo Clinic over the last 30 years. METHODS: Fourteen patients were
      identified who had resection of a mediastinal paraganglioma between 1973 and
      2007. Perioperative data obtained from the medical record and follow-up
      information were reviewed. RESULTS: The median age of patients at operation was
      39 years (range, 27 to 68 years), 71% were female, and all had a history of
      hypertension. Preoperative diagnosis of a catecholamine-secreting tumor was
      confirmed through elevated 24-hour urinary norepinephrine in 12 patients and
      tumor location was determined with metaiodobenzylguanidine scintigraphy, computed
      tomography or magnetic resonance imaging scans in the majority. The tumor was
      adjacent to the heart or great vessels in all patients and was resected through a
      median sternotomy (n = 10), or with posterolateral thoracotomy (n = 4). In 6
      patients, cardiopulmonary bypass was used to facilitate dissection of the
      paraganglioma from the heart or great vessels. There was one intraoperative death
      in this series due to blood loss. Ten of the 11 patients were alive at follow-up
      (median follow-up: 2.3 years; range, 0 to 19.4 years). Symptoms of catecholamine
      excess were eliminated or greatly improved in all patients who had a functioning
      tumor preoperatively, but 6 of these patients were still being treated with
      antihypertensive medications. CONCLUSIONS: Functional paragangliomas can be
      diagnosed with measurement of fractionated catecholamines and metanephrines;
      mediastinal localization is determined with appropriate scanning techniques.
      These tumors can be treated successfully by surgical resection with modest
      surgical risk, often necessitating cardiopulmonary bypass, with good long-term
      survival. Hypertension may persist even after complete resection of the tumor.

PMID- 18721589
TI  - Routine use of minimally invasive surgery for pectus excavatum in adults.
AB  - BACKGROUND: The Nuss operation, a minimally invasive repair of pectus excavatum,
      is considered the treatment of choice in children. It is controversial in adults,
      but smaller series have been published. We have used the Nuss operation routinely
      in adults since 2003. METHODS: The indication for operation was a patient
      described disabling cosmetic appearance. We modified the operation by using a
      shorter pectus bar, which appears to be more stable. All patient records were
      available and analyzed retrospectively. RESULTS: Operations for pectus excavatum
      were done in 475 patients (89% men) at Aarhus University Hospital. 180 patients
      (38%) were aged 18 years or older, median patient age was 22 years (range, 18 to
      43 years). All but one patient achieved an excellent cosmetic result. Two pectus
      bars were required in 57 patients (32%), and 2 patients required 3 pectus bars.
      The median duration of the procedure was 41 minutes (range, 16 to 119 minutes),
      which was significantly longer compared with younger patients, but the difference
      was not clinically relevant (6 minutes). Pneumothorax occurred in 86 patients
      (48%), but only 4 (2%) required chest tube drainage. In 3 patients the pectus bar
      dislocated during follow-up. CONCLUSIONS: Minimally invasive repair for pectus
      excavatum can be performed safely in adults, with excellent immediate cosmetic
      results. Adults often require more than 1 pectus bar. From the results of this
      large series, we conclude that patients aged younger than 50 years are eligible
      for minimally invasive surgical correction of pectus excavatum.

PMID- 18721590
TI  - Invited commentary. Despite many years of successful surgical repair, the field
      of pectus deformity remains controversial.

PMID- 18721591
TI  - Foreign bodies in pleura and chest wall.
AB  - BACKGROUND: In contrast to other locations, foreign bodies in pleura and chest
      wall have been rarely reported and there is no consensus with regard to
      treatment. METHODS: Between 1971 and 2001, 22 patients with foreign bodies in
      pleura or chest wall were admitted to our department. Their charts were reviewed
      for preoperative diagnosis, history, kind and location of the foreign bodies,
      length of retention, management of patients, and complications. RESULTS: Three
      etiologic groups were identified: iatrogenic (11 patients), traumatic-intentional
      (10), and accidental (1). Foreign bodies were extracted in 21 patients: at
      thoracotomy in 6, direct pleuroscopy in 6, video-thoracoscopy in 4, and simple
      incision in 5. One foreign body was left behind because of objection of parents.
      There were no complications and no deaths. Follow-up lasted from one year to 7
      years in 15 patients (68.2%). Seven patients did not show for follow-up.
      CONCLUSIONS: Foreign bodies should be removed from pleura and chest wall, when
      possible. Small, blunt, peripherally located foreign bodies may be left behind if
      difficulties at extraction are anticipated. Thoracotomy may be needed for
      treatment of associated injuries, and for removal of materials used in plombage,
      because of adhesions. In others the use of videothoracoscopy is preferable.
      Physicians performing diagnostic and therapeutic procedures in anatomic proximity
      of pleura should exert utmost care to avoid iatrogenic introduction of a foreign
      body.

PMID- 18721592
TI  - Spontaneous pneumomediastinum: a comparative study and review of the literature.
AB  - BACKGROUND: Spontaneous pneumomediastinum (SPM) is an unusual occurrence with few
      cases reported. It is seen after intrathoracic pressure changes leading to
      alveolar rupture and dissection of air along the tracheobronchial tree. This
      study was undertaken to provide a thorough clinical and radiologic analysis of
      this patient population. METHODS: A retrospective comparative analysis was
      performed on patients with SPM over 12 years. Patient demographics, clinical
      presentation, and radiographic and diagnostic studies were recorded. A clinical
      and radiologic comparison was performed with secondary pneumomediastinum.
      RESULTS: Seventy-four patients were identified with a diagnosis of
      pneumomediastinum. A total of 28 patients with SPM were identified. The major
      initial complaints were chest pain (54%), shortness of breath (39%), and
      subcutaneous emphysema (32%). The main triggering events were emesis (36%) and
      asthma flare-ups (21%). No apparent triggering event was noted in 21% of
      patients. Chest radiograph was diagnostic in 69%; computed tomography was
      required in 31%. Esophagram, esophagoscopy, and bronchoscopy were performed on an
      individual basis and were invariably negative. When compared with secondary
      pneumomediastinum, SPM is more likely to be discovered by chest radiography, has
      a lower incidence of pneumothorax and pleural effusion, requires a shorter
      hospital stay, and has no associated mortality. CONCLUSIONS: Spontaneous
      pneumomediastinum is a benign condition that often presents with chest pain or
      dyspnea. It can develop without a triggering event and with no findings on chest
      radiography. Treatment is expectant and recurrence is low. Secondary causes must
      be ruled out to avoid an unfavorable outcome.

PMID- 18721593
TI  - Morphologic assessment of extracellular matrix scaffolds for patch tracheoplasty
      in a canine model.
AB  - BACKGROUND: The optimal management of benign tracheal stricture remains surgical
      resection. Resection is not always an option because of the challenges posed by
      anastomotic tension and a tenuous blood supply. Regenerative medicine approaches,
      such as extracellular matrix (ECM) scaffold technology, may alleviate some of the
      limitations to tracheal replacement. ECM scaffolds facilitate site-specific
      tissue remodeling when used to reconstruct a variety of soft-tissue structures.
      METHODS: A 1-cm wide x 2-cm-long defect was created in the ventral trachea of 15
      dogs and repaired with one of three acellular biologic scaffolds: urinary bladder
      matrix (UBM), UBM crosslinked with carbodiimide (UBMC), and decellularized
      tracheal matrix (DTM). The grafts were evaluated periodically using bronchoscopy
      and by macroscopic and microscopic morphologic examination at either 2 months or
      6 months. RESULTS: The UBM, UBMC, and DTM groups showed no evidence of stenosis
      or tracheomalacia. The UBM, UBMC, and DTM groups all showed deposition of
      organized collagenous tissue at the site of scaffold placement and an intact
      epithelial layer. Scattered areas of mucociliary differentiation were present at
      the edges of the graft site. There was no evidence cartilage observed within the
      remodeled tissue at 6 months. CONCLUSIONS: ECM scaffolds promote healing of
      significantly sized tracheal defects without stricture and with some, but not
      all, of the necessary structures required for tracheal reconstruction, including
      complete coverage with ciliated epithelium and dense organized collagenous
      tissue.

PMID- 18721594
TI  - Revisional surgery after esophagectomy: an analysis of 43 patients.
AB  - BACKGROUND: Reflux and postprandial fullness are common after esophagectomy. On
      occasion, these symptoms have an anatomic basis that requires operative
      correction. Two such conditions are the following: (1) a diaphragmatic hernia in
      which bowel herniates into the chest; and (2) a redundant conduit that impairs
      gastric emptying. The recognition of these conditions and the results of
      operative correction are the subject of this analysis. METHODS: A retrospective
      review from 1995 to 2007 identified patients who developed either a diaphragmatic
      hernia or a redundant gastric conduit after esophagectomy. The presenting
      symptoms, operative approach, and outcomes after surgery were recorded. RESULTS:
      Forty-three patients (representing 4% of the esophagectomy volume in this time
      period) were identified with a diaphragmatic hernia (n = 21), redundant gastric
      conduit (n = 19), or both (n = 3). Mean time from esophagectomy to diagnosis was
      32 months for diaphragmatic hernia and 18 months for redundant conduit. The
      majority of hernias occurred to the left of the gastric conduit. A mechanical
      obstruction to gastric emptying was noted in 54% of patients with a redundant
      conduit. Forty patients underwent revisional surgery (minimally invasive: 35;
      open: 5). The recurrence rate after repair of a diaphragmatic hernia was 29%.
      Symptoms improved in 85% of patients after revision of a redundant conduit.
      CONCLUSIONS: A diaphragmatic hernia or redundant conduit may occur years after
      esophagectomy. Hernias almost always occur adjacent to the greater curve of the
      stomach. The development of a redundant conduit may be associated with a
      functional outflow obstruction. Surgical correction of these conditions can
      alleviate symptoms in the majority of patients.

PMID- 18721595
TI  - Coupled pacing reverses the effects of persistent atrial fibrillation on the left
      ventricle.
AB  - PURPOSE: Recent studies have demonstrated that ventricular rate control is a
      viable treatment strategy for patients in atrial fibrillation (AF). The purpose
      of this study was to determine whether or not the benefits of coupled pacing (ie,
      a proposed rate control therapy) could be used during persistent AF. DESCRIPTION:
      Six mongrel dogs were chronically implanted with endocardial atrial and
      ventricular pacemaker leads and two standard dual-chamber pacemakers. With the
      use of two custom "Y"-lead adapters, the pacemakers were used to induce AF and to
      apply coupled pacing. Left ventricular end-diastolic and systolic volumes were
      measured by echocardiography to determine ejection fractions. EVALUATION:
      Persistent AF significantly increased both ventricular rate and left ventricular
      dimensions. After sustained coupled pacing had been applied for 3 to 4 weeks,
      left ventricular volumes and contractile rate were significantly reduced and
      returned toward the values measured prior to the induction of persistent AF.
      Coupled pacing increased the ejection fraction that had been reduced by
      persistent AF. CONCLUSIONS: Coupled pacing reversed the left ventricular
      remodeling caused by the tachycardia resulting from AF.

PMID- 18721596
TI  - Invited commentary. Coupled ventricular pacing in a canine model of persistent
      atrial fibrillation.

PMID- 18721597
TI  - Thoracoscopic construction of an intrathoracic esophagogastric anastomosis using
      a circular stapler: transoral placement of the anvil.
AB  - PURPOSE: The purpose of this study is to describe a novel technique for
      thoracoscopic construction of an intrathoracic esophagogastrostomy using a
      circular stapler. DESCRIPTION: Conventional method for construction of the
      esophagogastric anastomosis requires placement of the anvil through an esophageal
      stump and securing it with a pursestring suture. Advances in stapler technology
      now permit the anvil to be placed transorally and positioned at the esophageal
      stump without the need for a pursestring suture. EVALUATION: Ten patients
      underwent laparoscopic and thoracoscopic esophagectomy with construction of an
      intrathoracic esophagogastric anastomosis using a circular stapler technique. The
      anvil was placed transorally in all patients without difficulty. There were no
      operative complications or postoperative leaks. CONCLUSIONS: The transoral
      placement of the anvil during thoracoscopic construction of an
      esophagogastrostomy is technically feasible and may facilitate the performance of
      the esophagogastric anastomosis using a circular stapler.

PMID- 18721598
TI  - Invited commentary. A method for circular stapled esophagogastric anastomosis.

PMID- 18721599
TI  - Coronary artery spasm: a rare but important cause of postoperative myocardial
      infarction.
AB  - Myocardial infarction that is attributed to native coronary artery spasm in the
      early postoperative phase has rarely been documented. We report three cases of
      postoperative myocardial infarction secondary to angiographically demonstrated
      coronary spasm. Native coronary artery spasm is a rare, but important cause of
      postoperative ischemia and infarction. Suspicious electrocardiographic changes
      warrant consideration of transesophageal echocardiography to detect unexpected
      wall motion abnormalities. Established treatments include intravenous or
      intracoronary infusion of nitroglycerin and calcium channel antagonists, although
      several new therapeutic agents may also be beneficial. Prompt coronary
      angiography is the only definitive modality for early diagnosis and targeted
      treatment.

PMID- 18721600
TI  - Percutaneous treatment of periprosthetic mitral valve leaks: is it just a futile
      exercise?
AB  - We report the percutaneous exclusion of a mitral peri-prosthetic valvular leak
      performed with the Amplatzer vascular plug. Device dislodgement occurred a few
      days later and surgical repair was ultimately required.

PMID- 18721601
TI  - Highly fenestrated septum primum leads to failure of Amplatzer septal defect
      closure.
AB  - A patient presenting with a history of transient ischemic attacks was initially
      diagnosed with a large secundum-type atrial septal defect by transesophageal
      echocardiography. Subsequent attempts to percutaneously repair the defect using
      an Amplatzer septal occlude device (AGA Medical, Plymouth, MN) failed to position
      correctly on multiple attempts. At the time of surgery, a largely deficient and
      highly fenestrated septum primum was found, which was likely the cause of the
      Amplatzer device (AGA Medical) failure. The defect was then definitively repaired
      using a bovine pericardial patch without incident.

PMID- 18721602
TI  - Intraventricular patch repair through an extended aortotomy for repeated left
      ventricular rupture after mitral valve replacement.
AB  - Posterior wall rupture of the left ventricle is a rare but lethal complication
      after mitral valve replacement. We treated a patient with repeated left
      ventricular rupture. Initially, type 1 left ventricular rupture was repaired in
      the intensive care unit, but persistent bleeding occurred after the repair. We
      treated the bleeding through an extended aortotomy and successfully repaired the
      repeated type 3 left ventricular rupture with bovine pericardium (Synovis
      Surgical Innovations Inc, St. Paul, MN).

PMID- 18721603
TI  - Emergency surgery after saphenous vein graft perforation complicated by catheter
      balloon entrapment and hemorrhagic shock.
AB  - Emergency surgery for acute vein graft perforation and balloon entrapment during
      percutaneous angioplasty is reported here. Prompt extracorporeal circulation
      through peripheral cannulation enabled the control of systemic perfusion despite
      cardiac arrest. Vein graft repair was achieved by an autologous pericardial
      patch. Appropriate and tailored mechanical circulatory support allowed successful
      extracorporeal circulation withdrawal, limited intraoperative cardiac damage, and
      postoperative controlled recovery of ventricular function with ultimate favorable
      outcome.

PMID- 18721604
TI  - Endomyocardial fibrosis in an adult mimicking left ventricular mass.
AB  - Endomyocardial fibrosis is a rare condition that occurs primarily in tropical
      countries. It can often mimick a variety of other common cardiac conditions such
      as apical hypertrophic cardiomyopathy and Ebstein anomaly. We report a case of a
      left ventricular mass that at histologic examination was found to be
      endomyocardial fibrosis.

PMID- 18721605
TI  - Right atrial chemodectoma with atypical chest pain: a 6-year surgical follow-up.
AB  - Paragangliomas are rare neoplasms of neural crest origin and arise from the
      chromaffin (pheochromocytomas) or chemoreceptor (chemodectomas) tissues. Patients
      with cardiac chemodectomas, hormonally inactive paragangliomas, may have chest
      pain or various obstructive or compressive symptoms, depending on the location of
      the tumor. We report the case of a right atrial chemodectoma causing atypical
      chest pain. The tumor was discovered at transthoracic echocardiography. Coronary
      angiography showed a vascular tumor fed by a branch of the circumflex artery. En
      bloc tumor resection was carried out under cardiopulmonary bypass, with an
      uneventful surgical course. After 6 years of follow-up, the patient remains
      asymptomatic and disease-free.

PMID- 18721606
TI  - Emergency surgery for left atrial metastatic alveolar rhabdomyosarcoma
      manifesting as a right atrial mass.
AB  - We report the case of a 43-year-old woman with a history of alveolar
      rhabdomyosarcoma of the forearm, scalp, and paraspinal region who developed acute
      shortness of breath owing to a tumor arising from the left atrium and extending
      through the coronary sinus. This was causing partial obstruction across the
      tricuspid valve as a result of the ball-valve effect. Emergency resection of the
      atrial mass was performed, and histologic analysis confirmed the presence of
      metastatic rhabdomyosarcoma. To our knowledge, this is the first reported case of
      emergency surgical resection of intracardiac metastatic alveolar
      rhabdomyosarcoma.

PMID- 18721607
TI  - Missing left atrial thrombus: dislodgement or artifact?
AB  - Patients with a left atrial thrombus are considered at high risk of
      thromboembolism. Surgical treatment is generally recommended. We experienced a
      case of a patient with a history of cerebral embolism related to chronic atrial
      fibrillation in whom, unexpectedly, no thrombi were found at thrombectomy.
      Although echocardiography is a useful method for detection of a thrombus in the
      left atrium, the possibility of a reverberation artifact should be routinely
      explored.

PMID- 18721608
TI  - Reconstruction of large post-sternotomy wound with bilateral "V-Y fasciocutaneous
      advancement flaps".
AB  - Post-sternotomy wounds are highly dangerous complications after a median
      sternotomy. Many different methods have been described for reconstruction of post
      sternotomy wounds. The treatment is multifactorial. The treatment depends on the
      severity of the wound and various patient factors. We evaluate a novel method for
      closure of sternal dehiscence of a patient who has multiple comorbid problems,
      including diabetes mellitus, hypertension, and chronic obstructive pulmonary
      disease. In our method, after debridement, the "bilateral V-Y fasciocutaneous
      advancement flaps" were used for reconstruction. This method presents a
      successful resolution of an infected median sternotomy wound. It is a simple,
      rapid, and effective procedure associated with low mortality, morbidity, and
      short hospital stay.

PMID- 18721609
TI  - Transverse plate fixation of sternum: a new sternal-sparing technique.
AB  - We report 2 cases of vacuum-assisted closure therapy and thoracic reconstruction
      using new sternum titatium plates in patients with deep sternal wound infection
      after median sternotomy. The specific advantage of this new approach is
      anatomical reduction of the sternum that prevents paradoxical movement and severe
      anterior chest instability, and improves postoperative outcome.

PMID- 18721610
TI  - Right-sided univentricular cardiac assistance in a failing Fontan circulation.
AB  - Fontan patients are doomed to a circulatory failure and many of them will require
      a circulatory assistance as a bridge to transplantation. The univentricular heart
      with a total cavopulmonary connection presents a special challenge for the
      insertion of an assist device. We report a patient in multiple organ dysfunction
      and failure who was supported by right-sided univentricular assistance.
      Technically, a new chamber was created between both vena cava for implantation of
      the inflow cannula, and the extracardiac conduit was used to set the outflow
      cannula. The patient dramatically recovered and is currently in the best
      condition for heart transplantation.

PMID- 18721611
TI  - Successful repair of a subtotal rupture of distal tracheobronchial tree with
      complete abridgment of the right bronchus in a 4-year-old child.
AB  - Accurate diagnosis of tracheobronchial injuries in children is difficult due to
      the paucity of clinical presentation and the variety of clinical symptoms. They
      are potentially life threatening in blunt chest trauma. We report here on a
      clinical case of a boy who was injured during outdoor activity. We describe
      intraoperative findings of the massive tracheobronchial lesion and its successful
      repair using a pericardial patch technique and postoperative recovery. Such a
      serious tracheobronchial injury with a positive outcome has not been reported so
      far. Clinical and technical steps are described and discussed.

PMID- 18721612
TI  - Bronchopleural fistula repair using combined breast parenchymal and pectoralis
      major musculocutaneous flap.
AB  - A technique is reported for repair of a bronchopleural fistula and obliteration
      of an empyema cavity using a combined breast parenchymal and expanded,
      musculocutaneous pectoralis major flap. An empyema after right upper lobectomy
      and radiation for squamous cell carcinoma developed in a 53-year-old woman. After
      debridement, a bronchopleural fistula was noted. Her latissimus dorsi muscle was
      divided during the initial thoracotomy. Local and free flaps were considered. Her
      breast contained the largest volume of tissue available as she weighed 80 pounds.
      This report illustrates the use of a tissue-expanded, combined breast and
      musculocutaneous pectoralis flap in the management of a difficult problem.

PMID- 18721613
TI  - A rare case of primary pleomorphic adenoma in main bronchus.
AB  - Primary pleomorphic adenoma of the lung is a rare occurrence. Clinical suspicion
      is normally low due to its rarity. We describe a case of a primary pleomorphic
      adenoma arising from the origin of the right main bronchus and include our
      management strategy.

PMID- 18721614
TI  - Transperitoneal migration of an abdominal epicardial pacemaker.

PMID- 18721615
TI  - Total anomalous pulmonary connection with an unusual drainage.

PMID- 18721616
TI  - Simultaneous lung and spine impalement from a fractured humerus after blunt
      trauma.

PMID- 18721617
TI  - Brain protection by using innominate artery cannulation during aortic arch
      surgery.
AB  - The innominate artery cannulation (IAC) through the same sternotomy incision was
      used for 68 patients with aneurysm, involving the ascending aorta or the aorta
      arch. The IAC can get adequate flows during cooling and re-warming of
      cardiopulmonary bypass. It can also provide sufficient antegrade perfusion for
      brain during hypothermia circulation arrest. There is no relative complication
      noted for the technique, and we believe it is a simple and effective alternative.

PMID- 18721618
TI  - A novel technique of supra-annular mitral valve replacement.
AB  - We describe a new technique of mitral valve replacement in an 11.5-month-old, 5.5
      kg baby whose native mitral annulus was only 14 mm. We successfully implanted a
      16-mm mechanical valve in the supra-annular position by sewing it into a short
      polytetrafluoroethylene graft that was then sutured to the native annulus.

PMID- 18721619
TI  - Novel retractor for lymph node dissection by video-assisted thoracic surgery.
AB  - In nonrandomized studies, the video-assisted thoracic surgical (VATS) lobectomy
      seems to be a safe and effective procedure for treatment of lung cancer. However,
      there are some difficulties in VATS complete mediastinal lymph node dissection.
      The presence of the lymph node deep in the mediastinal space necessitates
      retraction of the surrounding organs. Therefore, we developed a retractor to
      create enough working space during the VATS procedure. To dissect lymph nodes, we
      use endoscopic bipolar forceps. These instruments are connected to a special
      electrosurgical generator to apply bipolar soft coagulation, which enables
      simultaneous dissection and sealing. Thus, "en bloc" lymph node dissection can be
      performed during the VATS procedure.

PMID- 18721620
TI  - Efficacy and safety of recombinant activated factor VII to control bleeding in
      nonhemophiliac patients: a review of 17 randomized controlled trials.
AB  - We reassess all published randomized controlled trials that have evaluated the
      hemostatic efficacy or safety of recombinant activated factor VII (rFVIIa), or
      both, in nonhemophiliac patients. Seventeen trials published in 16 articles dealt
      either with the prophylactic (nine trials) or the therapeutic (eight trials) use
      of rFVIIa to prevent or to treat excessive bleeding. At present, the role of
      rFVIIa to prevent or to control bleeding and reduce transfusions in various
      patient populations remains unclear. In addition, the safety of rFVIIa remains a
      concern. Consequently, we conclude that the generalized use of rFVIIa to prevent
      or to control bleeding in nonhemophiliac patients can not be recommended.

PMID- 18721621
TI  - Coronary artery bypass grafting after previous stenting is associated with
      compromised long-term efficacy.

PMID- 18721624
TI  - Do different techniques of left internal mammary graft harvesting really affect
      hospital outcome?

PMID- 18721625
TI  - Postoperative complications after cardiac surgery and HIT: a word of caution.

PMID- 18721627
TI  - Bioglue: a word of caution.

PMID- 18721629
TI  - Brachial cannulation instead of axillary and subclavian cannulation.

PMID- 18721631
TI  - The pectoralis major myocutaneous flap in mediastinal tracheostomy
      reconstruction.

PMID- 18721633
TI  - Postoperative pneumonia after major pulmonary resections: the importance of
      gastrointestinal tract management.

PMID- 18721635
TI  - One-session treatment of specific phobias: a detailed description and review of
      treatment efficacy.
AB  - One-Session Treatment (OST) is a form of massed exposure therapy for the
      treatment of specific phobias. OST combines exposure, participant modeling,
      cognitive challenges, and reinforcement in a single session, maximized to three
      hours. Clients are gradually exposed to steps of their fear hierarchy using
      therapist-directed behavioral experiments. Although there are several studies in
      the literature examining the efficacy of OST, little has been done to summarize
      this research. In the following review, research on and empirical support for OST
      are reviewed with an emphasis on the types of stimuli, samples, and methodologies
      utilized. Research generally supports OST's efficacy, although replication by
      independent examiners using adult and child samples is needed using more rigorous
      comparisons (e.g., psychological placebo or other treatments). Overall, OST
      continues to be a promising treatment for specific phobias; however, a great deal
      more investigation is needed to identify mechanisms of change, mediators, and
      moderators.

PMID- 18721636
TI  - Moving beyond an exclusive focus on harm avoidance in obsessive compulsive
      disorder: considering the role of incompleteness.
AB  - Cognitive-behavioral conceptualizations of obsessive compulsive disorder (OCD)
      have predominantly viewed compulsions as being motivated by harm avoidance.
      However, sensations of things being incomplete or not "just right" may also
      underlie compulsions in OCD. Preliminary research suggests that distinguishing
      between harm avoidance and incompleteness in OCD may have practical utility, but
      the research on this topic is very limited to date. The current study further
      addressed the role of incompleteness in OCD. A confirmatory factor analysis
      provided evidence for harm avoidance and incompleteness as separate constructs in
      a student sample. Supporting the benefits of considering incompleteness in
      addition to harm avoidance, self-reported levels of both constructs were
      significantly correlated with all domains of OCD symptoms and perfectionism
      assessed. Further, some evidence for unique relationships was found (e.g.,
      incompleteness with ordering and personally prescribed perfectionism; harm
      avoidance with obsessing). The role of incompleteness in OCD warrants greater
      attention.

PMID- 18721638
TI  - An open trial of a transdiagnostic cognitive-behavioral group therapy for anxiety
      disorder.
AB  - Transdiagnostic models of anxiety, and cognitive-behavioral treatments based on
      these models, have been gaining increased attention in recent years. Preliminary
      efficacy studies generally suggest strong treatment effects, although few of
      these studies have examined to what extent treatment effects are similar across
      clients with different anxiety disorders. The purpose of the current study was to
      examine the efficacy of a 12-week transdiagnostic group cognitive-behavioral
      therapy for anxiety disorders and compare outcome across diagnoses. Mixed-effect
      regression modeling of data from 52 participants with anxiety disorders
      (predominantly panic disorder and social phobia) participating in an open outcome
      trial indicated that participants tended to improve over treatment, with no
      differential outcome for any primary or comorbid disorders. The results of this
      study add to the growing evidence base for transdiagnostic anxiety treatment
      models and provide preliminary support for the assumption that individuals with
      different anxiety diagnoses can be treated equally within the same treatment
      protocol.

PMID- 18721637
TI  - The relative contribution of abuse severity and PTSD severity on the psychiatric
      and social morbidity of battered women in shelters.
AB  - Intimate partner violence (IPV) is a severe health problem associated with
      significant distress and impairment in women. The most common psychiatric
      difficulty in battered women is posttraumatic stress disorder (PTSD); however, no
      research to date has investigated the relative impact of the severity of IPV and
      IPV-related PTSD symptoms on battered women's psychosocial functioning. In a
      sample of 177 sheltered battered women, PTSD severity was associated with
      considerable psychiatric morbidity, social maladjustment, and personal and social
      resource loss. Moreover, PTSD severity mediated the relationship between IPV
      severity and psychiatric severity and loss of personal and social resources.
      Results highlight the need for the assessment and treatment of IPV-related PTSD
      in battered women's shelters.

PMID- 18721639
TI  - An experimental investigation of the effect of worry on responses to a
      discrimination learning task.
AB  - The current study examined the impact of both the tendency to worry (trait worry)
      and the process of worry (state worry) on subsequent behavioral responding in a
      schedule discrimination learning task. High and low trait worriers were randomly
      assigned to a state worry or relaxation incubation condition and completed a test
      of executive functioning and a dual contingency learning task that utilized
      neutral discriminative cues over the course of 2 contingency phases. Although
      state and trait worry did not impact executive functioning, the state worry
      condition was associated with diminished sensitivity to learning task
      contingencies over the course of the first contingency learning trials in
      comparison to the relaxation condition. This relationship was unique to the state
      worry condition above and beyond shared variance with subjective anxiety level.
      Results suggest that state worry may lead to a decrement in selective behavioral
      responding to neutral discriminative cues in the environment. The findings
      suggest that the process of worry may lead to less adaptive responding to neutral
      cues and interfere with adaptive behaviors, which may thereby contribute to and
      maintain anxiety.

PMID- 18721640
TI  - The impact of pretrauma analogue GAD and posttraumatic emotional reactivity
      following exposure to the September 11 terrorist attacks: a longitudinal study.
AB  - The relation between analogue generalized anxiety disorder (GAD) assessed the day
      before the events of September 11, 2001 (9/11) and long-term outcome was examined
      in 44 young adults who were directly exposed the following day to the terrorist
      attacks in New York City. After controlling for high exposure to the attacks,
      preattack analogue GAD was associated with greater social and work disability,
      loss of psychosocial resources, anxiety and mood symptoms, and worry, but not
      symptoms of posttraumatic stress, assessed 12 months after 9/11. Fear and
      avoidance of emotions assessed 4 months after 9/11 statistically mediated the
      relation between preattack analogue GAD and social and work disability, loss of
      psychosocial support, mood and anxiety symptoms, and worry at 12-month follow-up.
      Avoidance of emotions 4 months after 9/11 also mediated the relation between
      preattack analogue GAD and posttraumatic stress symptoms 12 months after 9/11.

PMID- 18721641
TI  - The role of interdependence and perceived similarity in depressed affect
      contagion.
AB  - This study hypothesized that perceived similarity significantly impacts depressed
      affect contagion only for individuals with highly interdependent self-construals.
      Baseline self-construal and affect were measured. Then, after reading a vignette
      about a depressed or nondepressed target, affect and perceived similarity were
      assessed. Participants reading the depressed vignette reported higher negative
      affect than participants reading the nondepressed vignette. Positive affect did
      not differ between the two conditions. For participants exposed to the depressed
      vignette, the hypothesized interaction between perceived similarity and
      interdependence significantly predicted positive affect. It appears that
      participants with more interdependent self-construals were more likely to "catch"
      the low positive affect displayed by the depressed target only if they perceived
      themselves as highly similar to the target.

PMID- 18721643
TI  - Overperception of spousal criticism in dysphoria and marital discord.
AB  - Depression and marital discord are related to feeling criticized by others,
      especially by spouses (e.g., Hooley, J. M., & Teasdale, J. D. 1989). This study
      evaluated the extent to which criticism was overperceived in relation to "actual"
      spousal critical comments, with actual critical comments being established by
      independent observers and by criticizing spouses themselves. Using dyadic
      interaction and questionnaire data from 72 married couples, signal detection and
      regression analyses suggested that both dysphoria and marital discord were
      associated with a general bias towards feeling criticized. Marital discord's
      association with criticality bias subsumed dysphoria's, but dysphoria's did not
      subsume marital discord's. Criticality bias also accounted for a significant
      proportion of perceived spousal criticism. A common cognitive process may
      underlie established associations among perceived criticism, dysphoria, and
      marital discord.

PMID- 18721642
TI  - The pattern of subjective anxiety during in-session exposures over the course of
      cognitive-behavioral therapy for clients with social anxiety disorder.
AB  - Exposure-based therapies are efficacious treatments for social anxiety disorder
      (i.e., Gould et al., 1997). Much of the theory behind these treatments is derived
      from Foa and colleagues' (Foa, Huppert, & Cahill, 2005; Foa & Kozak, 1986) work
      on emotional processing. However, there has been little research examining
      individual differences in emotional processing patterns within and between
      treatment sessions among clients with social anxiety disorder. This study
      utilized longitudinal data analytic methods to examine changes in subjective
      anxiety during the first 3 exposure sessions in group and individual cognitive
      behavioral therapy for social anxiety disorder. The results of this study provide
      preliminary evidence that, although anxiety generally decreases across exposures,
      some individuals experience considerable fluctuations in anxiety during a single
      exposure. Although anxiety during the first exposure was not significantly
      related to outcome, the relationship between anxiety during exposure and outcome
      became stronger during subsequent exposures. Overall, this study highlights the
      need to conduct more fine-grained analyses to better understand the mechanisms
      underlying exposure-based therapies for social anxiety disorder.

PMID- 18721644
TI  - Quality improvement in electrocardiogram recording and interpretation.

PMID- 18721645
TI  - The influence of cardiograph design and automated algorithms on the incidence and
      detection of electrode cable reversals in an academic electrocardiogram
      laboratory.
AB  - BACKGROUND: Medical errors have been increasingly identified as a major source of
      morbidity and mortality in both outpatient and acute care settings. Central to
      the evaluation of many medical problems, the 12-lead electrocardiogram (ECG) is
      susceptible to both technical and interpretative errors. Proper interpretation,
      however, is dependent on the quality and accuracy of the acquired ECG. METHODS:
      We evaluated the impact of both a newly designed electrocardiograph and a newly
      developed automated computer algorithm on the incidence and detection of
      electrode cable reversals (lead reversals). The study tested the association of
      the incidence of electrode cable reversals and the design of the connection
      terminal. The study was performed during a 7-month period preceding (53,875 ECGs)
      and after (53,344 ECGs) the implementation of the new system. Electrode cable
      reversals occurring in various sites of the medical center were tabulated and
      compared. We then sought to determine if computer detection algorithms could
      increase point-of-care detection of electrode cable reversals and, thereby,
      offset the influence of cardiograph design changes. Two commercially available
      automated detection algorithms were compared for their abilities to identify
      electrode cable reversals in our study population. RESULTS: During the 7-month
      postimplementation period, there was a significant increase in the incidence in
      electrode cable reversals (0.5% vs 0.1%, P < .001). The incidence of reversals
      for ECGs obtained in the emergency department was twice that of those obtained
      within the hospital (0.79% vs 0.38%, P < .01). Automated detection of electrode
      cable reversals from the 7-month study period increased from 38% to 71% (P < or =
      .0001), using a recently released automated algorithm supplied by the
      manufacturer. CONCLUSIONS: Electrode cable reversals are a prevalent source of
      medical errors that receives very little attention by the clinical community. The
      association of an increase in electrode cable reversals with an altered electrode
      cable connection terminal, coupled with an increased ability to detect electrode
      cable reversals using the manufacturer's recently developed algorithms,
      emphasizes the importance of ongoing research efforts to identify technical
      errors in electrocardiography.

PMID- 18721646
TI  - Control of electrocardiogram acquisition errors: a brief perspective.

PMID- 18721647
TI  - New electrocardiographic diagnostic criteria for the pathologic R waves in leads
      V1 and V2 of anatomically lateral myocardial infarction.
AB  - AIMS: To study the different QRS patterns in leads V1 and V2 in first inferior,
      lateral, and combined inferolateral myocardial infarction (MI) to recognize which
      are the ECG criteria that best define the presence of lesions isolated to the
      anatomically lateral wall of the left ventricle. METHODS AND RESULTS: We studied
      consecutive patients with first inferior (15), lateral (9), or inferolateral (21)
      MI with reference to contrast enhanced cardiac magnetic resonance (CE-CRM). We
      measured the R-wave amplitude and duration, the R/S ratio, and the T-wave
      amplitude and polarity in leads V1 and V2. The specificity of the V1 criteria for
      lateral MI, that is, R/S amplitude ratio 1 or greater and R duration 40
      milliseconds or longer, is very high but its sensitivity is low. We defined 2 new
      criteria, R/S of 0.5 or greater and R amplitude in V1 greater than 3 mm, with
      each achieving a sensitivity of 73.3% and specificity of 93.3% for
      lateral/inferolateral MI location. CONCLUSIONS: (1) New ECG criteria for lateral
      MI (R/S ratio in V1 > or =0.5 and R amplitude in V1 >3 mm) present very high
      specificity and lower but very acceptable sensitivity for lateral MI. (2) New
      criteria based on R waves in V2 or T waves in V1 to V2 do not discriminate
      between inferior and lateral MI. (3) The classical criteria (R/S amplitude ratio
      > or =1 and R duration > or =40 ms in V1) attain very high specificity but much
      lower sensitivity than the new criteria.

PMID- 18721649
TI  - Medical clinics of North America. Women's health. Preface.

PMID- 18721650
TI  - Barriers to women's health: why is it so hard for women to stay healthy?
AB  - Women's health care has made great strides in the past two decades. The
      recognition that women have different health care needs than men has enabled
      changes to take place in clinical care, research, and education. However, much
      remains to be done. Providing health care coverage to all women must be a high
      priority. Research must address the differences between men and women and how
      they respond to disease and treatment. The physician workforce needs to be
      expanded; physicians should be well trained to provide comprehensive health care
      to women. Strategies, such as used in Comprehensive Centers of Women's Health and
      women's health residencies, can improve education and increase the number of
      women in academia.

PMID- 18721651
TI  - Preventive health for women: screening and immunizations.
AB  - Women's preventive health issues are frequently encountered in the outpatient
      setting. Many general internists feel uncomfortable meeting the needs of women
      due to a general lack of knowledge of women's health and inadequate training in
      the evaluation of female-specific care. In this article, the authors summarize
      evidence-based guidelines for preventive health and immunizations for women.

PMID- 18721652
TI  - Contraception: what every internist should know.
AB  - The human costs of unintended pregnancy-abortion and parenting under difficult
      circumstances-are high. For this reason, all physicians who treat female patients
      should be knowledgeable about the basics of contraception-both its practical uses
      and its public health impact. This knowledge will make physicians, including
      internists, better able to counsel and provide contraceptives for individual
      patients and to advocate for availability and access. This article discusses the
      problem and determinants of unintended pregnancy and reviews contraceptive
      methods.

PMID- 18721653
TI  - Preventing cervical cancer: the Pap test and the HPV vaccine.
AB  - Women look to their internists and other primary care physicians to provide
      preventive health care. Periodic Pap tests are as much a part of a woman's
      ongoing health care as periodic lipid assessments, mammograms, screening for
      colon cancer, or any of the other recommended screening assessments. This article
      provides primary care physicians with the information needed to perform Pap tests
      at the appropriate intervals, or if not set up to do Pap tests themselves, to
      make the appropriate referrals. Also provided is the necessary information to
      counsel women with abnormal Pap tests who may need colposcopy or other follow-up
      evaluation. Finally, the role of the HPV vaccine in the prevention of cervical
      cancer is summarized.

PMID- 18721654
TI  - Sexually transmitted infections and pelvic inflammatory disease in women.
AB  - Sexually transmitted infections (STIs) are an important public health challenge
      in the United States. Primary care clinicians can contribute to decreasing these
      largely preventable causes of morbidity and mortality by integrating routine
      screening, testing, counseling, treatment, and partner management of STIs into
      their practice. Newer tests for chlamydia and gonorrhea that can be performed on
      urine specimens allow screening without a pelvic examination. The most recent
      edition of the Centers for Disease Control and Prevention sexually transmitted
      disease treatment guidelines provides an evidence-based, reliable, and convenient
      set of recommendations for treating and caring for patients who have STIs.

PMID- 18721655
TI  - Breast disease: benign and malignant.
AB  - Breast diseases, both benign and malignant, are common. Typically, young women
      present with more benign pathologies; however, breast malignancies can occur in
      young women, especially in those harboring mutations in the BRCA genes, other
      inherited genetic syndromes associated with increased risk of breast cancer, or
      familial predisposition for breast cancer. In all women aged 40 and over
      presenting with abnormalities of the breast, a primary breast cancer should be
      ruled out because it is the leading cancer among women in developed countries.

PMID- 18721656
TI  - Pelvic masses.
AB  - Pelvic masses develop commonly in women of all ages and states of health. Despite
      the variety of masses that exist, general guidelines for diagnosis and management
      allow most masses to be treated in a generalist setting. This article is intended
      to guide non-obstetric and non-gynecologic physicians through diagnosis and
      treatment of nonmalignant pelvic masses. It includes information on physical
      examination, appropriate imaging techniques, laboratory tests, and variations in
      treatment for adolescents and pre- and postmenopausal women. It also addresses
      referral guidelines for suspected malignant masses.

PMID- 18721657
TI  - Basic infertility including polycystic ovary syndrome.
AB  - Infertility in women has many possible causes and must be approached
      systematically. The most common cause of medically treatable infertility is the
      polycystic ovary syndrome (PCOS). This syndrome is common in young women and is
      the cause of anovulatory infertility in 70% of cases. It is therefore an
      important condition to screen and manage in primary care medical settings. In the
      past 10 years, insulin sensitization with weight loss or metformin has been shown
      to be a safe and effective treatment for PCOS infertility that eliminates the
      risk of multiple pregnancy and may reduce the risk of early pregnancy loss as
      compared with ovulation-inductor drugs. The authors believe metformin should be
      considered as first-line therapy because it has the advantage to allow for normal
      single ovulation, for reduced early pregnancy loss, and, most importantly,
      lifestyle modifications and weight loss before pregnancy. Losing weight not only
      improves fertility but also reduces adverse pregnancy outcomes associated with
      obesity.

PMID- 18721658
TI  - Medical issues from preconception through delivery: a roadmap for the internist.
AB  - The age of the pregnant population and the number of pregnant women with medical
      issues are increasing. It is widely recognized that internists have the unique
      opportunity to identify potential pregnancy issues and address them before a
      problem arises. Therefore, it's important that we become aware of how to approach
      these issues. In addition to addressing medical issues in a currently pregnant
      woman, doctors also have the opportunity to identify issues that occurred during
      a prior pregnancy, such as gestational diabetes, preeclampsia, or pregnancy loss,
      and to decrease the risk of complications in future pregnancies. The goal of this
      article is to provide a roadmap to practicing internists so they will incorporate
      pregnancy planning into their everyday care plans. The approach is similar to
      that used when performing a preoperative risk assessment: We want to optimize our
      patients medically for pregnancy.

PMID- 18721659
TI  - Prescribing medications safely during pregnancy.
AB  - A large body of information about medications prescribed during pregnancy is
      readily available to internists and patients either on-line or through books and
      medical journals. Much of the evidence about many prescribed drugs is either
      anecdotal or presented with sufficient warnings about its use during pregnancy.
      This article discusses specific medications to set the risks and benefits into a
      more proper perspective, thereby alleviating certain fears and, when necessary,
      improving compliance.

PMID- 18721660
TI  - Domestic violence and rape.
AB  - No compilation of women's health care is complete without confronting domestic
      violence and sexual assault. Long recognized as a health care and physician
      issue, intimate partner violence continues to be one of the most frequent causes
      for injury and death to women in the United States and worldwide. According to
      the Commonwealth Fund survey in 1998, 31% of women reported either physical or
      sexual abuse from a husband or boyfriend. One in five American women also
      reported being raped during their lifetime. Careful assessment and universal
      screening are important tools for the primary care physician.

PMID- 18721661
TI  - Menopause and the menopausal transition.
AB  - Menopause and the menopausal transition present unique preventive health and
      quality-of-life challenges for women. The number of patients in the menopausal
      age group is increasing and represents a significant portion of the population.
      Care of the menopausal patient can be challenging for the caregiver. This chapter
      reviews the major health care challenges as well as evaluation and treatment of
      common quality-of-life issues for menopausal patients.

PMID- 18721662
TI  - Urinary incontinence and pelvic organ prolapse: diagnosis and treatment for the
      primary care physician.
AB  - This article outlines a simplified approach to diagnosis and treatment of women
      with urinary incontinence or pelvic organ prolapse that can be used by primary
      care physicians to identify patients with these conditions and initiate treatment
      for basic problems.

PMID- 18721663
TI  - [Introduction].

PMID- 18721664
TI  - [Psoriasis news at the Paris Dermatology Days 2007].
AB  - Clinical research works on Psoriasis presented at 2007 annual dermatological
      meeting in Paris are synthesized in this paper. Efficacy of new treatment,
      quality of life, extracutaneous lesions of psoriasis and relations between
      psoriasis and other inflammatory diseases were the main topics.

PMID- 18721665
TI  - [What are the objectives of moderate to severe psoriasis treatment?].
AB  - Psoriasis is a potentially severe and highly disabling systemic disease. Over the
      last few years, large international randomized trials on biotherapies have made
      it possible to rigorously assess patients' quality of life. Moreover, combining
      patient groups has been organized in Europe and elsewhere, which has allowed
      large-scale studies structured around psoriasis patient expectations. A review of
      these studies provides information on patient expectations so that they can be
      transformed into therapeutic objectives. Through studies conducted on infliximab,
      it has been shown that this type of new treatment can respond to a large part of
      patient demand.

PMID- 18721666
TI  - [Severe psoriasis: beyond the skin, what are the risks of not treating the
      disease?].
AB  - Psoriasis is a systemic inflammatory disease whose cutaneous involvement is the
      most visible component. Treating the skin and the psychological effects is the
      main objective of today's treatments. However, the discovery of comorbidities and
      their effects on the frequently associated cardiac and cerebral vascular risk and
      on metabolic syndrome has led to substantial modification of patient management
      and to new therapeutic strategies. This review of the comorbidities associated
      with cutaneous psoriasis and the impacts of systemic treatments for psoriasis on
      these comorbidities aims to outline what the future may hold in terms of patient
      management.

PMID- 18721667
TI  - [What are the risks of not intensively treating a chronic inflammatory disease?].
AB  - With more than 10 years of experience in rheumatology and thousands of patients
      treated, the infectious and oncological risks of TNF-alpha blocking agents are
      well known. The efficacy of biotherapies in rheumatismal diseases has been
      largely demonstrated. The recent review of publications and communications shows
      that biotherapies benefit the comorbidities associated with inflammatory
      rheumatisms (uveitis, Crohn disease, hemorrhagic rectocolitis, stroke, myocardial
      infarction). They can even reduce the excess mortality of chronic rheumatoid
      inflammatory diseases.

PMID- 18721668
TI  - Synergistic anti-hyperalgesia of electroacupuncture and low dose of celecoxib in
      monoarthritic rats: involvement of the cyclooxygenase activity in the spinal
      cord.
AB  - Electroacupuncture (EA) can effectively control the exaggerated pain in humans
      with inflammatory disease and animals with experimental inflammatory pain.
      However, there have been few investigations on the effect of co-administration of
      EA and analgesics and the underlying synergistic mechanism. Using behavioral
      test, RT-PCR analysis, enzyme immunoassay (EIA) and enzyme-linked immunosorbent
      assay (ELISA), the present study demonstrated that (1) Unilateral intra-articular
      injection of complete Freund's adjuvant (CFA) produced a constant hyperalgesia
      and an up-regulation of the prostaglandin E(2) (PGE(2)) level as well as the
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 levels in the
      spinal cord; (2) Celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2), at
      a dose of 2, 10, and 20 mg/kg (twice daily, p.o.), presented a dose-dependent
      anti-hyperalgesic effect; (3) Repeated EA stimulation of ipsilateral 'Huan-Tiao'
      (GB30) and 'Yang-Ling-Quan' (GB34) acupoints significantly suppressed CFA-induced
      hyperalgesia, and markedly inhibited the CFA-induced increase of the level of
      PGE(2) as well as IL-1beta, IL-6, and TNF-alpha in the spinal cord; (4) EA
      combined with low dose of celecoxib (2 mg/kg, twice daily, p.o.) greatly enhanced
      the anti-hyperalgesic effects of EA, with a synergistic reversing effect on CFA
      induced up-regulation of spinal PGE(2), but not on the IL-1beta, IL-6, or TNF
      alpha. These data indicated that repeated EA combined with low dose of celecoxib
      produced synergistic anti-hyperalgesic effect in the CFA-induced monoarthritic
      rats, which could be made possible by regulating the activity of spinal COX,
      hence the spinal PGE(2) level. Thus, this combination may provide an effective
      strategy for pain management.

PMID- 18721669
TI  - Haloperidol (but not ziprasidone) withdrawal potentiates sensitization to the
      hyperlocomotor effect of cocaine in mice.
AB  - One important contributing factor in the high prevalence of drug abuse disorders
      seen among schizophrenic patients seems to be related to chronic treatment with
      typical neuroleptics. We have previously demonstrated that withdrawal from long
      term treatment with the typical neuroleptic haloperidol, but not the atypical
      neuroleptic ziprasidone, potentiated the hyperlocomotor effect induced by a
      single cocaine injection and cocaine-induced conditioned place preference in
      mice. In the present study we investigated whether withdrawal from long-term
      treatment with these same neuroleptics would also modify cocaine-induced
      hyperlocomotion sensitization, which has been proposed as an animal model for the
      intensification of drug craving in cocaine addiction. Swiss male mice were i.p.
      treated with haloperidol (1.0 mg/kg) or ziprasidone (4.0 mg/kg) for 15 days.
      Twenty-four hours after the last injection, animals received an i.p. injection of
      cocaine (10 mg/kg) for 5 consecutive days, being placed after each injection in
      the open-field apparatus in order to perform a drug-environment conditioning.
      Seven days after the last drug-environment conditioning procedure, the animals
      were challenged with an i.p. injection of cocaine (10 mg/kg), placed in the open
      field apparatus and had their locomotor activity quantified. Withdrawal from
      haloperidol (but not ziprasidone) potentiated cocaine-induced behavioral
      sensitization. These results are suggested to be a consequence of the development
      of the dopaminergic supersensitivity phenomenon by long-term treatment with the
      typical compound. Our findings provide additional support for the use of atypical
      agents like ziprasidone in the treatment of schizophrenic patients with comorbid
      substance abuse disorder.

PMID- 18721670
TI  - Neurotensin modulation of acetylcholine, GABA, and aspartate release from rat
      prefrontal cortex studied in vivo with microdialysis.
AB  - The effects of the peptide transmitter neurotensin (NT) on the release of
      acetylcholine (ACh), gamma-aminobutyric acid (GABA), glutamate (Glu), aspartate
      (Asp), and taurine from the prefrontal cortex (PFC) of freely moving rats were
      studied by transversal microdialysis. Neurotensin (0.2 and 1 microM) administered
      locally in the PFC produced a concentration-dependent increase in the
      extracellular levels of ACh, GABA, and Asp, but not of Glu or taurine. The
      increase produced by 1 microM NT reached a maximum of about 240% for ACh, 370%
      for GABA, and 380% for Asp. Lower doses of NT (0.05 microM) did not cause a
      significant change in ACh, GABA, or Asp output in the PFC. Higher concentrations
      of NT (2 microM) did not induce further increases in the level of
      neurotransmitters. A high-affinity selective neurotensin receptor (NTR1)
      antagonist SR 48692 (0.5 microM) perfused locally blocked neurotensin (1 microM)
      evoked ACh, GABA, and Asp release. Local infusion of the sodium channel blocker
      tetrodotoxin (TTX) (1 microM) decreased the release of ACh, had no significant
      effect on GABA or Asp release, and prevented the 1 microM neurotensin-induced
      increase in ACh, GABA, and Asp output. Removal of calcium from the Ringer's
      solution prevented the peptide from having any effects on the neurotransmitters.
      Thus, in vivo NT plays a modulatory role in the PFC by interacting with cortical
      neurons releasing GABA and Asp and with ACh-containing neurons projecting to the
      PFC. The NT effects are of neural origin, as they are TTX-sensitive, and mediated
      by the NTR1 receptor, as they are antagonized by SR 48692.

PMID- 18721671
TI  - Culture-independent methods for identifying microbial communities in cheese.
AB  - This review focuses on the culture-independent methods available for the
      description of both bacterial and fungal communities in cheese. Important steps
      of the culture-independent strategy, which relies on bulk DNA extraction from
      cheese and polymerase chain reaction (PCR) amplification of selected sequences,
      are discussed. We critically evaluate the identification techniques already used
      for monitoring microbial communities in cheese, including PCR-denaturing gradient
      gel electrophoresis (PCR-DGGE), PCR-temporal temperature gradient gel
      electrophoresis (PCR-TTGE) or single-strand conformation polymorphism-PCR (SSCP
      PCR) as well as some other techniques that remain to be adapted to the study of
      cheese communities. Further, our analysis draws attention to the lack of data
      available on suitable DNA sequences for identifying fungal communities in cheese
      and proposes some potential DNA targets.

PMID- 18721672
TI  - Effect of oenological practices on microbial populations using culture
      independent techniques.
AB  - Sulphur dioxide (SO(2)) addition and yeast inoculation are well-established
      practices in winemaking for restricting the growth of indigenous yeasts and
      bacterial populations. The effect of these oenological practices on wine
      microbial populations has been evaluated using culture-independent methods. These
      are quantitative PCR (qPCR) for the enumeration of yeasts, lactic acid bacteria
      (LAB) and acetic acid bacteria (AAB), and PCR-DGGE to determine the yeast and
      bacteria species diversity. The PCR-DGGE method detected a low yeast and bacteria
      species diversity. On the contrary, the specificity of the primers designed for
      the qPCR allowed that minor microbial groups such as Hanseniaspora were
      accurately quantified regardless of a large presence of other microbial groups
      such as Saccharomyces. From an oenological point of view, inoculation increased
      the proportion of Saccharomyces vs. non-Saccharomyces in a shorter time.
      Hanseniaspora increased during the first phase and decreased during the latter
      phases of the process, especially in the sulphited fermentations. Both yeast
      inoculation and SO(2) kept the LAB populations at very low level, while the AAB
      populations were hardly affected by these two practices.

PMID- 18721674
TI  - Effect of combining nisin and/or lysozyme with in-package pasteurization for
      control of Listeria monocytogenes in ready-to-eat turkey bologna during
      refrigerated storage.
AB  - This study investigated the efficacy of in-package pasteurization combined with
      pre-surface application of nisin and/or lysozyme to reduce and prevent the
      subsequent recovery and growth of Listeria monocytogenes during refrigerated
      storage on the surface of low-fat turkey bologna. Sterile bologna samples were
      treated with solutions of nisin (2 mg/ml=5000 AU/ml), lysozyme (10 mg/ml=80
      AU/ml) and a mixture of nisin and lysozyme (2 mg nisin+10mg lysozyme/ml) before
      in-package pasteurization at 65 degrees C for 32s. In-package pasteurization
      resulted in an immediate 3.5-4.2 log CFU/cm(2) reduction in L. monocytogenes
      population for all treatments. All pasteurized treatments also resulted in a
      significant reduction of L. monocytogenes by 12 weeks compared to un-pasteurized
      bologna. In-package pasteurization in combination with nisin or nisin-lysozyme
      treatments was effective in reducing the population below detectable levels by 2
      3 weeks of storage. Results from this study could have a significant impact for
      the industry since a reduction in bacterial population was achieved by a
      relatively short pasteurization time and antimicrobials reduced populations
      further during refrigerated storage.

PMID- 18721673
TI  - Inactivation kinetics of inoculated Escherichia coli O157:H7, Listeria
      monocytogenes and Salmonella Poona on whole cantaloupe by chlorine dioxide gas.
AB  - The objectives of this study were to examine inactivation kinetics of inoculated
      Escherichia coli O157:H7, Listeria monocytogenes and Salmonella Poona inoculated
      onto whole cantaloupe and treated with ClO(2) gas at different concentrations
      (0.5, 1.0, 1.5, 3.0 and 5.0 mg l(-1)) for different times (0, 2.0, 4.0, 6.0, 8.0
      and 10.0 min). The effect of ClO(2) gas on the quality and shelf life of whole
      cantaloupe was also evaluated during storage at 22 degrees C for 12 days. A 100
      microl inoculation of each targeted organism was spotted onto the surface (5
      cm(2)) of cantaloupe rind (approximately 8-9 log CFU 5 cm(-2)) separately, air
      dried (60 min), and then treated with ClO(2) gas at 22 degrees C and 90-95%
      relative humidity for 10 min. Surviving bacterial populations on cantaloupe
      surfaces were determined using a membrane transferring method with a non
      selective medium followed by a selective medium. The inactivation kinetics of E.
      coli O157:H7, L. monocytogenes and S. Poona were determined using nonlinear
      kinetics (Weibull model). A 3 log CFU reduction of E. coli O157:H7, L.
      monocytogenes and S. Poona were achieved with 5.0 mg l(-1) ClO(2) gas for 5.5,
      4.2 and 1.5 min, respectively. A 5l og CFU reduction of S. Poona was achieved
      with 5.0 and 3.0 mg l(-1) ClO(2) gas for 6 and 8 min, respectively. A 4.6 and 4.3
      log reduction was achieved after treatment with 5.0 mg l(-1) ClO(2) gas at 10 min
      for E. coli O157:H7 and L. monocytogenes, respectively. Treatment with 5.0 mg l(
      1) ClO(2) gas significantly (p<0.05) reduced the initial microflora (mesophilic
      bacteria, psychrotrophic bacteria, and yeasts and molds) on cantaloupe by more
      than 2 log CFU cm(-2) and kept them significantly (p<0.05) lower than the
      untreated control during storage at 22 degrees C for 12 days. Treatment with
      ClO(2) gas did not significantly (p>0.05) affect the color of whole cantaloupe
      and extended the shelf life to 9 days compared to 3 days for the untreated
      control, when stored at ambient temperature (22 degrees C).

PMID- 18721675
TI  - The reduction of murine norovirus 1, B. fragilis HSP40 infecting phage B40-8 and
      E. coli after a mild thermal pasteurization process of raspberry puree.
AB  - Pasteurization processes of raspberry puree are nowadays limited to short times
      and rather low temperatures to maintain flavor and nutritional quality. Norovirus
      (NoV) outbreaks associated with raspberries highlight the need to determine the
      survival of NoV on this type of soft fruit. Therefore, resistance of murine
      norovirus 1 (MNV-1), a surrogate for human NoV, B. fragilis HSP40 infecting phage
      B40-8, and E. coli towards mild pasteurization was tested. Raspberry puree heat
      treated at 65 degrees C for 30s showed a 1.86, 2.77, and 3.89 log reduction of,
      respectively, MNV-1, E. coli, and B40-8. Heating at 75 degrees C for 15s
      established a 2.81 log reduction of MNV-1 while a 3.44 and 3.61 log reduction of
      B40-8 and E. coli was observed. No supplementary lethal effect of holding the
      heat-treated raspberry puree at 4 degrees C overnight was noticed. B40-8 failed
      to be useful as a tool to monitor NoV inactivation during mild pasteurization
      processes. Moreover, <3 log reductions of MNV-1 were observed suggesting that
      upon high initial contamination load, infectious NoV particles may remain on
      mildly pasteurized raspberry puree.

PMID- 18721676
TI  - Occurrence of lactic acid bacteria and biogenic amines in biologically aged
      wines.
AB  - Biologically aged sherry-type wines are elaborated by the so-called 'criadera and
      solera' system, which essentially involves development of the yeast on the wine
      surface forming a film velum for several years. Lactic acid bacteria can also
      develop and contribute to sherry-type wine quality, although their presence and
      role in this enological process have received very little attention. In this
      study, lactic acid bacteria microbiota and the presence of biogenic amines were
      investigated throughout the manufacture and biological aging of 36 samples of
      sherry wines. Malolactic fermentation was found to mainly take place during the
      first stage of biological ageing. The incidence and populations of lactic acid
      bacteria in sherry wines were low. The diversity of bacterial species isolated
      from the wines was greater than previously reported and included species of
      Lactobacillus, with prevailing Lactobacillus hilgardii, Lactobacillus plantarum
      and Lactobacillus zeae and Leuconostoc mesenteroides. The biogenic amine
      producing capacity of the isolates was also determined. Five strains were
      putrescine producers, while another strain was shown to produce tyramine and
      phenylethylamine, simultaneously. L. zeae was one of the predominant species in
      wines during the biological aging and seemed to be one of the main putrescine
      producers. The biogenic amine composition of the wines investigated was similar
      to that reported for other types of wines. Putrescine was the major amine,
      followed by cadaverine, histamine and tyramine. The amine contents detected were
      lower than those usually reported in red wines.

PMID- 18721677
TI  - Comparative survey of putrescine production from agmatine deamination in
      different bacteria.
AB  - This article aims to study putrescine production in Lactobacillus hilgardii
      strain X(1)B, an agmatine degrader isolated from wine, and to compare it with
      three other different species, previously reported as putrescine producers from
      agmatine: Pseudomonas aeruginosa PAO1, Enterococcus faecalis ATCC11700 and
      Bacillus cereus CECT 148(T). The effect of different biogenic amines, organic
      acids, cofactors, amino acids and sugars on putrescine production was evaluated.
      In some cases, a similar effect was found in all the strains studied but the
      magnitude differed. Arginine, glucose and fructose showed an inhibitory effect,
      whereas the presence of agmatine induced the production of putrescine in all
      microorganisms. In other cases, the effect differed between P. aeruginosa PAO1
      and the other microorganisms. Histamine and tyramine poorly influenced the
      utilization of agmatine, although a small increase in putrescine production was
      observed in P. aeruginosa PAO1. Succinate, spermidine and spermine also led to an
      increase in putrescine production in P. aeruginosa PAO1, whereas the succinate
      had no effect in the other microorganisms. Spermine and spermidine always
      produced a diminution in agmatine deamination. In this work, we have also
      demonstrated that pyridoxal 5-phosphate, Mg(2+) and Mn(2+) had no effect on
      putrescine production from agmatine. Results presented in this paper indicate
      differences in regulation mechanisms of agmatine deiminase pathway among P.
      aeruginosa PAO1 and L. hilgardii X(1)B, E. faecalis ATCC11700 and B. cereus CECT
      148(T). These results are significant from two points of view, first food
      quality, and second the toxicological and microbiological aspects. It should be
      taken into account that putrescine, whose origin is still controversial, is
      quantitatively the main biogenic amine found in food.

PMID- 18721678
TI  - Effect of poultry decontaminants concentration on growth kinetics for pathogenic
      and spoilage bacteria.
AB  - Various chemical compounds are currently under review for final approval as
      poultry decontaminants in the European Union (EU). Concentration is among the
      factors considered by the EU authorities in the evaluation of these treatments.
      The aim of this research was to compare the growth parameters for pathogenic and
      spoilage bacteria in presence of high and low concentrations of poultry
      decontaminants to assess whether such treatments could involve a potential
      sanitary risk for consumers. Growth curves for Salmonella enterica serotype
      Enteritidis, Listeria monocytogenes, Pseudomonas fluorescens and Brochothrix
      thermosphacta were obtained at different levels of trisodium phosphate (TSP;
      1.74%; 0.58%), acidified sodium chlorite (ASC; 210 ppm; 70 ppm) and citric acid
      (CA; 0.27%; 0.09%). The modified Gompertz equation was used as primary model to
      fit observed data. ASC and TSP were the most effective compounds in increasing
      lag phase (L) and reducing maximum growth rate (mu) in Gram-negative bacteria.
      Gram-positive bacteria were more influenced by CA. At high TSP levels, mu for
      Salmonella decreased. Low TSP levels increased mu for Salmonella and Listeria
      relative to control samples. In presence of 0.27% CA, Brochothrix showed the
      highest L and the lowest mu among strains tested. These results suggest that low
      TSP and high CA concentrations could favour the outgrowth of pathogenic bacteria
      (e.g. Salmonella) relative to spoilage bacteria, rending these treatments
      potentially dangerous for consumers. The findings of this study may be useful to
      the EU authorities and meat processors in their efforts to select adequate
      treatments for control of bacteria on poultry.

PMID- 18721679
TI  - Optimised quantification of the antiyeast activity of different barley malts
      towards a lager brewing yeast strain.
AB  - The brewing of beer involves two major biological systems, namely malted barley
      (malt) and yeast. Both malt and yeast show natural variation and assessing the
      impact of differing malts on yeast performance is important in the optimisation
      of the brewing process. Currently, the brewing industry uses well-established
      tests to assess malt quality, but these frequently fail to predict malt
      associated problem fermentations, such as incomplete fermentations, premature
      yeast flocculation (PYF) and gushing of the final beer product. Antimicrobial
      compounds, and in particular antiyeast compounds in malt, may be one of the
      unknown and unmeasured malt factors leading to problem fermentations. In this
      study, the adaptation of antimicrobial assays for the determination of antiyeast
      activity in malt is described. Our adapted assay was able to detect differing
      antiyeast activities in nine malt samples. For this sample set, malts associated
      with PYF during fermentation and gushing activity in beer showed high antiyeast
      activity. Both PYF and gushing are malt quality issues associated with fungal
      infection of barley in the field which may result in elevated antimicrobial
      activity in the barley grain. Also, two more malts that passed the normal quality
      control tests were also observed to have high antiyeast activity and such malts
      must be considered as suspect. Based on our results, this assay is a useful
      measure of malt quality as it quantifies the antiyeast activity in malt which may
      adversely impact on brewery fermentation.

PMID- 18721680
TI  - Distributions of the growth rate of the germ tubes and germination time of
      Penicillium chrysogenum conidia depend on water activity.
AB  - The effects of water activities for sporulation (a(wsp)) and germination (a(wge))
      on the distributions of the growth rate of the germ tubes (mu) and the
      germination time (t(G)) of Penicillium chrysogenum conidia were determined by
      monitoring the length of the same germ tubes throughout the experiments
      automatically. No relationship between the individual t(G)'s and mu's could be
      established. Irrespective of the water activity for germination, mu was greater
      and t(G) was less for conidia produced at 0.95a(wsp) than that at 0.99a(wsp). At
      0.99 a(wge) the mean and the standard deviation of t(G) were smaller than those
      obtained at 0.95a(wge). At 0.99a(wge), normal distributions for mu and t(G) were
      exhibited, but not at 0.95a(wge). The cumulative frequencies were used to
      reconstruct the germination curves. Great differences in the percentage of spores
      capable of germination (P(G)) and in the mean germination times between conidia
      produced at 0.95a(wsp) and at 0.99a(wsp) were clearly exhibited at 0.95a(wge),
      thus demonstrating the paramount influence of sporulation conditions on
      germination kinetics.

PMID- 18721681
TI  - PCR assay for the detection of Campylobacter in marinated and non-marinated
      poultry products.
AB  - During a period of 9 months, 194 marinated and non-marinated poultry products
      were collected from retail shops in a defined area in Western Finland and tested
      for Campylobacter spp. using a conventional enrichment culture and Polymerase
      Chain Reaction (PCR) method. For marinated poultry products, the study involved
      modification of a commercial DNA isolation method. Using either a conventional
      culture or PCR method, a total of 25 (12.9%) of all investigated samples were
      Campylobacter positive. In marinated poultry products, Campylobacter was detected
      at a prevalence of 21.1% and 9.5% in turkey and chicken products, respectively.
      In August, there was a peak with 28.9% positive Campylobacter samples.
      Campylobacter inoculation tests were carried out to test the detection limit of
      both methods. The PCR method used is faster than microbiological analyses.
      However, enrichment of the samples is necessary due to the low occurrence of
      Campylobacter spp. in retail Finnish poultry products.

PMID- 18721682
TI  - Control of spoilage microorganisms in minced pork by a self-developed modified
      atmosphere induced by the respiratory activity of meat microflora.
AB  - The changes in microbial flora of minced pork during aerobic storage at 0, 5, 10
      and 15 degrees C were studied. Minced pork samples (100g) were packed using two
      types of packaging films: (a) a common food film with high permeability (HPF) and
      (b) a film with low permeability (LPF). The respiratory activity of meat
      microflora and the use of a LPF resulted in a modified atmosphere in the package
      headspace developed during storage. Oxygen concentration decreased from 18.7%
      (after packaging) to 7% (after 15 days of storage) in packages with LPF, stored
      at 0 degrees C, while CO(2) increased from 3% to 10.5%, respectively. On the
      contrary, no significant atmosphere changes were observed during storage of HPF
      packages. The self-developed modified atmosphere in LPF packages resulted in a
      significant inhibition of pseudomonad growth which was more pronounced at low
      storage temperatures. For example, during storage at 0 degrees C, the growth rate
      of pseudomonads in meat packed with LPF was reduced by 48.7% compared to HPF. At
      10 degrees C the latter reduction decreased to 13.7%. LPF packaging was also
      found to inhibit the growth of Brochothrix thermosphacta but this inhibition was
      weaker compared to pseudomonads. The effect of storage temperature on the growth
      rate of pseudomonads and B. thermosphacta in minced pork packed with the
      different films was modeled using an Arrhenius equation. For both bacteria, the
      activation energy was higher for LPF packaging. This can be attributed to the
      increased inhibitory effect of the modified atmosphere at lower storage
      temperature. The Arrhenius model was further used to evaluate the effect of
      temperature on the time required by the two bacteria to reach a spoilage level of
      10(7)CFU/g. The results showed that when LPF packaging is combined with effective
      temperature control the time-to-spoilage can be significantly extended compared
      to HPF packaging.

PMID- 18721683
TI  - Antimicrobial effects of chitosans and chitooligosaccharides, upon Staphylococcus
      aureus and Escherichia coli, in food model systems.
AB  - The objective of this study was to elucidate the controversial relationship
      between the molecular weight (MW) of chitosans and their antibacterial activity
      (upon different inoculum levels, at several concentrations). The influence of
      food components on the activity was also ascertained, as well as acceptance by a
      sensory panel. All the compounds tested exhibited antibacterial activity against
      Staphylococcus aureus and Escherichia coli. This activity was shown to be closely
      dependent on the inoculum level, MW and concentration used. Within 4h at 10(3)
      cells/mL, all five compounds, at every concentration (0.5%, 0.25% and 0.1%, w/v),
      proved to be bactericidal; for higher inocula, 0.1% (w/v) was only
      bacteriostatic; at 10(7) or 10(5) cells/mL, and independently of the inoculum
      level, 0.25% (w/v) of any chitooligosaccharide (COS) mixture was sufficient to
      reduce the E. coli initial population by at least 3 log cycles; COS never
      exhibited bactericidal action over S. aureus, unlike high and medium MW chitosans
      which, at 0.5% (w/v), presented a bactericidal effect even against 10(7)
      cells/mL. When incorporated in liquid food matrices, medium and high MW chitosans
      maintained their activity, for both matrices and bacteria, although a slower
      activity was noticeable in milk; however, COS lost their activity upon both
      bacteria in milk after 4-8h. Furthermore, addition of chitosans to apple juice
      led to several unpleasant off-flavors, such as astringency and after taste--which
      increased in magnitude with MW.

PMID- 18721684
TI  - Diversity of lactic acid bacteria in two Flemish artisan raw milk Gouda-type
      cheeses.
AB  - PCR-denaturing gradient gel electrophoresis (PCR-DGGE) was used to study the
      diversity of lactic acid bacteria (LAB) in two Flemish artisan raw milk Gouda
      type cheeses. In parallel, conventional culturing was performed. Isolates were
      identified using (GTG)(5)-PCR and sequence analysis of 16S rRNA and pheS genes.
      Discriminant analysis revealed some differences in overall LAB diversity between
      the two batches and between the two cheeses. Within each batch, the diversity of
      8- and 12-week-old cheeses was relatively similar. Conventional isolation mainly
      revealed the presence of Lactobacillus paracasei, Lactobacillus plantarum,
      Lactobacillus brevis, Lactobacillus rhamnosus and Pediococcus pentosaceus. PCR
      DGGE revealed the presence of three species of which no isolates were recovered,
      i.e. Enterococcus faecalis, Lactobacillus parabuchneri and Lactobacillus
      gallinarum. Conversely, not all isolated bacteria were detected by PCR-DGGE. We
      recommend the integrated use of culture-dependent and -independent approaches to
      maximally encompass the taxonomic spectrum of LAB occurring in Gouda-type and
      other cheeses.

PMID- 18721685
TI  - Combined effects of heat, nisin and acidification on the inactivation of
      Clostridium sporogenes spores in carrot-alginate particles: from kinetics to
      process validation.
AB  - Combined effects of mild temperatures, acidification and nisin on the thermal
      resistance of Clostridium sporogenes ATCC 11437 spores were assessed. Inoculated
      carrot-alginate particles were used as a solid-food model for the validation of
      the spore inactivation during the flow of a solid-liquid food system through the
      holding tube of an aseptic processing unit. Inactivation kinetics was studied in
      a water bath with the spores inoculated into carrot-alginate particles and in
      Sorensen's phosphate buffer. For temperatures of 70-90 degrees C, D-values in the
      buffer were 24.9-5.7 min, much lower than those evaluated for the particles
      (115.1-22.2 min). Statistical analyses showed significant synergistic effects of
      temperature and pH on spore inactivation for both media. Acidification reduced
      the heat resistance of the spores by reducing the D-values. Nisin was not
      significantly effective at the lower concentrations (up to 750 IU/g). The
      combination of 90 degrees C, pH: 4.5 and 500IU/g nisin resulted in a ten-fold
      decrease of the D-value for spores inoculated in the particles (from 111.1 to
      10.6 min). Microbial validation tests were conducted using a pilot-scale aseptic
      processing unit with a mixture of carrot cubes (10%) and carrier liquid of 2%
      carboxymethylcellulose solution (90%). Spore-inoculated carrot-alginate particles
      (initial counts of 106 CFU/g, obtained after come-up-time pre-heat) with pH 3.5
      and 2000 IU/g nisin were processed at 90 degrees C in the aseptic processing
      unit. Microbial analysis showed no spore survivors in the particles after passing
      through the holding tube (5.2-6.0 min of residence time). The proposed
      combination of these hurdles significantly enhanced the spore inactivation rate
      (D(90)=1.17 min) as compared to that for thermal treatment only (D(90)=19.6 min).

PMID- 18721686
TI  - Intraspecific genetic diversity of lactic acid bacteria from malolactic
      fermentation of Cencibel wines as derived from combined analysis of RAPD-PCR and
      PFGE patterns.
AB  - Three molecular techniques, randomly amplified polymorphic DNA-polymerase chain
      reaction (RAPD-PCR), pulsed field gel electrophoresis (PFGE) and differential
      display-polymerase chain reaction (DD-PCR) have been used to assess the
      intraspecific diversity of the lactic microbiota responsible for spontaneous
      malolactic fermentation (MLF) in Cencibel wines made at a cellar in Castilla-La
      Mancha (Spain). The results indicate that RAPD-PCR and PFGE are of value in
      typing this microbiota. Better discrimination was achieved by RAPD-PCR.
      Reproducibility using DD-PCR was not good, which makes this method unsuitable.
      Combined numerical analysis of the patterns obtained from RAPD-PCR and PFGE
      allowed a better discrimination; this would therefore be a suitable tool to
      discriminate the diversity of bacterial communities like those found in MLF of
      wines. Genetic diversity data from combined numerical analysis suggest that there
      is considerable microbial diversity within MLF of Cencibel wines, with some
      genotypes coinciding in the two vinifications analysed.

PMID- 18721687
TI  - Impact of citation practices: beyond journal impact factors.

PMID- 18721689
TI  - Technique for removing OVD to prevent CBS.

PMID- 18721690
TI  - Central thickness variation in precut DSAEK donor grafts.

PMID- 18721691
TI  - Endothelial cell loss after pIOL implantation for high myopia.

PMID- 18721692
TI  - Oil-drop cataracts.

PMID- 18721693
TI  - Astigmatism terminology.

PMID- 18721695
TI  - Consultation section. Refractive surgical problem.

PMID- 18721701
TI  - Fibrin glue-assisted sutureless posterior chamber intraocular lens implantation
      in eyes with deficient posterior capsules.
AB  - We report a new surgical technique that uses biological glue to implant a
      posterior chamber intraocular lens (PC IOL) in eyes with a deficient or absent
      posterior capsule. Two partial-thickness limbal-based scleral flaps are made 180
      degrees apart diagonally, and the haptics of the PC IOL are externalized to place
      them beneath the flaps. Fibrin glue is used to attach the haptics to the scleral
      bed, beneath the flap. This simple method of PC IOL implantation requires no
      specially designed haptics. It provides good flap closure and IOL centration and
      stability without suture-related complications.

PMID- 18721703
TI  - Evaluation of the safety of prophylactic intracameral moxifloxacin in cataract
      surgery.
AB  - PURPOSE: To evaluate posterior and anterior segment safety of an intracameral
      injection of moxifloxacin 0.5% ophthalmic solution as prophylaxis for
      endophthalmitis in patients having cataract surgery. SETTING: Three private
      practices, the University of Minnesota School of Medicine, Stillwater, Minnesota,
      and the University of Cincinnati, Cincinnati, Ohio, USA. METHODS: In this
      prospective randomized combined-center open-label trial, 57 eyes of 47 patients
      were treated with intracameral moxifloxacin (250 mug/0.050 mL) or an equal volume
      of balanced salt solution at the conclusion of cataract surgery with intraocular
      lens implantation. Safety parameters, including visual acuity, intraocular
      pressure, endothelial cell counts, corneal pachymetry, corneal clarity and edema,
      and anterior chamber cells and flare, were evaluated preoperatively and for 3
      months postoperatively. RESULTS: Optical coherence tomography results showed no
      statistically significant differences between the 2 treatment groups
      preoperatively or at 3 months. There were also no statistically significant
      differences between the 2 treatment groups in all other parameters preoperatively
      or at 1 day, 2 to 4 weeks, or 3 months. No study-related adverse events occurred.
      CONCLUSION: There was no increased safety risk associated with a 250 mug/0.050 mL
      intracameral injection of moxifloxacin, which appears to be safe in the
      prophylaxis of endophthalmitis after cataract surgery.

PMID- 18721702
TI  - Laboratory diagnosis of endophthalmitis: comparison of microbiology and molecular
      methods in the European Society of Cataract & Refractive Surgeons multicenter
      study and susceptibility testing.
AB  - PURPOSE: To investigate and compare the use of molecular biology with the use of
      traditional Gram stain and organism culture for the laboratory diagnosis of
      postoperative endophthalmitis. SETTING: Twenty-four ophthalmology units together
      with 9 microbiology laboratories and 2 European reference molecular biology
      laboratories. METHODS: A prospective randomized partially masked multicenter
      cataract surgery study recruited 16 603 patients. This resulted in 29 cases of
      presumed postoperative endophthalmitis. Gram stain and culture were performed in
      the local laboratory according to agreed protocols. Samples of aqueous and/or
      vitreous were transported to the first referenced molecular biology laboratory
      (Regensburg, Germany) for polymerase chain reaction (PCR) testing, and an
      extracted aliquot of DNA was then referred to the second laboratory (Alicante,
      Spain) for PCR. RESULTS: Of the 29 who presented with presumed postoperative
      endophthalmitis, 20 were classified as proven infective endophthalmitis with
      positive Gram stain, culture, or PCR. Fourteen patients were culture-positive;
      all but 1 of these was also positive by PCR. Six patients were positive by PCR
      but negative by Gram stain or culture. Nine patients were negative by both
      microbiology and PCR testing. CONCLUSIONS: Use of molecular biology technique
      increased the laboratory rate of identifying the pathogen by 20%, confirming the
      technique is very useful for the endophthalmitis specimen. Samples of both
      aqueous and vitreous should be collected and stored at -20 degrees C for PCR at
      the time of the diagnostic taps.

PMID- 18721704
TI  - Third- and fourth-generation fluoroquinolones: retrospective comparison of
      endophthalmitis after cataract surgery performed over 10 years.
AB  - PURPOSE: To determine differences in endophthalmitis rates with prophylactic use
      of third- versus fourth-generation fluoroquinolones in cataract surgery. SETTING:
      University hospitals. METHODS: This retrospective cross-sectional (prevalence)
      study looked at patients who had phacoemulsification at a university eye center
      over a 10-year period. A nosocomial infectious reporting database was used to
      report endophthalmitis occurrences. The following were performed: a retrospective
      analysis of prospectively collected data to establish endophthalmitis rates, a
      prevalence analysis of the postoperative quinolone antibiotic prescribed, and a
      comparative analysis of endophthalmitis rate versus postoperative quinolone
      prescribed for all reported endophthalmitis cases. The main outcome measure was
      occurrence of endophthalmitis after cataract surgery. RESULTS: From January 1997
      to December 2007, 29276 patients had phacoemulsification cataract surgery. Forty
      cases of postoperative bacterial endophthalmitis were reported. The
      endophthalmitis rate from January 1997 to August 2003 associated with use of
      third-generation fluoroquinolones (ciprofloxacin, ofloxacin) was 0.197%
      (33/16710). The rate from September 2003 to December 2007 associated with fourth
      generation fluoroquinolones (gatifloxacin, moxifloxacin) was 0.056% (7/12566).
      The difference between third- and fourth-generation drugs was statistically
      significant (P = .0011). Of fourth-generation fluoroquinolone infections, 0.015%
      (1/6651) and 0.1% (6/5915) were associated with gatifloxacin and moxifloxacin,
      respectively. The difference between drugs was statistically significant (P =
      .040). CONCLUSIONS: The differences in the pharmacokinetic and pharmacodynamic
      properties of quinolone antibiotics may affect the endophthalmitis incidence
      after cataract surgery. The significant difference in endophthalmitis rates
      between gatifloxacin and moxifloxacin requires further study.

PMID- 18721705
TI  - Microincision multifocal intraocular lens with and without a capsular tension
      ring: optical quality and clinical outcomes.
AB  - PURPOSE: To study the effect of a capsular tension ring (CTR) on the visual,
      refractive, and intraocular optical quality of a multifocal intraocular lens
      (IOL) with diffractive asymmetrical light distribution. SETTING: Vissum-Instituto
      de Oftalmologico de Alicante, Alicante, Spain. METHODS: An Acri.Lisa 366D IOL was
      implanted without CTR implantation in 54 eyes (Group 1) or with Acri. Ring BR 11
      CTR implantation in 40 eyes (Group 2). Intraocular optical quality in vivo was
      characterized by the difference between the postoperative total and corneal
      optical aberrations. Visual, refractive, and intraocular optical outcomes were
      evaluated 3 months postoperatively. Main outcome measures included postoperative
      residual refraction, uncorrected and corrected far and near visual acuities,
      intraocular aberrations, the Strehl ratio, and the modulation transfer function
      (MTF). RESULTS: The postoperative means in Group 1 were spherical equivalent,
      0.31 +/- 0.45 diopters (D); uncorrected distance acuity, 0.79 +/- 0.19; best
      corrected distance acuity, 0.95 +/- 0.11; uncorrected near acuity, 0.77 +/- 0.21;
      best corrected near acuity, 0.89 +/- 0.14; best distance-corrected acuity, 0.90
      +/- 0.12. The Group 2 means were -0.18 +/- 0.60 D, 0.74 +/- 0.23, 0.98 +/- 0.07,
      0.72 +/- 0.22, 0.86 +/- 0.14, and 0.86 +/- 0.14, respectively. Group 2 had a
      statistically significant reduction in intraocular aberrations and a significant
      increase in MTF values and Strehl ratios compared with Group 1. CONCLUSION:
      Combined use of the CTR and Acri.Lisa 366D IOL provided good efficacy,
      predictability, and safety and increased the intraocular optical performance,
      suggesting better IOL stability.

PMID- 18721706
TI  - Long-term follow-up of a multifocal apodized diffractive intraocular lens after
      cataract surgery.
AB  - PURPOSE: To report the long-term performance of the AcrySof ReSTOR SA60D3
      intraocular lens (IOL) after cataract surgery. SETTING: University Hospital
      Maastricht, Maastricht, The Netherlands. METHODS: This prospective clinical trial
      comprised 44 eyes (22 consecutive patients) having cataract surgery with
      implantation of the ReSTOR IOL. Monocular and binocular uncorrected distance
      visual acuity, best corrected distance visual acuity, uncorrected near visual
      acuity, best distance-corrected near visual acuity, spectacle dependence,
      undesired visual symptoms, patient satisfaction, and incidence of posterior
      capsule opacification were analyzed 6 months and 3 years postoperatively.
      RESULTS: The mean uncorrected distance acuity (logMAR) was 0.046 +/- 0.099 at 6
      months and 0.115 +/- 0.173 at 3 years and the mean best corrected distance
      acuity, -0.040 +/- 0.075 and -0.018 +/- 0.093, respectively. Binocular
      uncorrected and best-corrected near acuities (logMAR) were 0.009 +/- 0.029 at 6
      months and 0.014 +/- 0.035 at 3 years. All patients achieved a binocular
      uncorrected and best distance-corrected near acuity of 20/25 or better at 6
      months and 3 years. On a quality-of-life questionnaire, patients reported good
      distance, intermediate, and near acuity without complaints of severe glare or
      halos. Complete spectacle independence for distance and near acuity was achieved
      by 83.7% and 81.9% of patients, respectively, at 6 months and 85.0% and 75.0% of
      patients, respectively, at 3 years. Four eyes (9.1%) required neodymium:YAG
      capsulotomy. CONCLUSIONS: Cataract surgery with the AcrySof ReSTOR SA60D3 IOL
      provided good, stable distance and near visual acuities over a 3-year follow-up,
      leading to low spectacle independence and high patient satisfaction.

PMID- 18721707
TI  - Astigmatism management in cataract surgery with the AcrySof toric intraocular
      lens.
AB  - PURPOSE: To present clinical data from a single-center prospective clinical trial
      of the AcrySof toric intraocular lens (IOL). SETTING: Academic Hospital
      Maastricht, Maastricht, The Netherlands. METHODS: Fifty-three eyes (43 patients)
      had implantation of an AcrySof toric IOL. Three toric models were evaluated in
      cylinder powers of 1.50 diopters (D) (SN60T3; T3 group, n = 16), 2.25 D (SN60T4;
      T4 group, n = 14), and 3.00 D (SN60T5; T5 group, n = 23) at the IOL plane. The T5
      group was subdivided into eyes that could be fully corrected (T5a, n = 13) and
      eyes that could be partially corrected (T5b, n = 10). RESULTS: Four months
      postoperatively, the mean uncorrected visual acuity (UCVA) was 0.77 +/- 0.23 in
      the T3 group, 0.93 +/- 0.23 in the T4 group, 0.82 +/- 0.15 in the T5a group, and
      0.47 +/- 0.13 in the T5b group. More than 90% of the combined eyes in the T3, T4,
      and T5a groups achieved a UCVA of 20/40 or better, and almost 80% achieved a UCVA
      of 20/25 or better. Residual refractive astigmatism of less than 0.75 D was
      achieved in 74% of eyes and of less than 1.00 D in 91%. The mean IOL misalignment
      was 2.5 +/- 2.1 degrees in the T3 group, 3.5 +/- 2.3 degrees in the T4 group, and
      4.1 +/- 3.5 degrees in the T5 group. CONCLUSION: Implantation of the AcrySof
      toric IOL proved to be an effective, safe, and predictable method of managing
      corneal astigmatism in cataract patients.

PMID- 18721708
TI  - Fellow-eye comparison of posterior capsule opacification with AcrySof SN60AT and
      AF-1 YA-60BB blue-blocking intraocular lenses.
AB  - PURPOSE: To evaluate intraindividual differences in posterior capsule
      opacification (PCO) and visual performance of AcrySof SN60AT (Alcon Laboratories)
      and AF-1 YA-60BB (Hoya Corp.) intraocular lenses (IOLs). SETTING: Ophthalmology
      Department, St. Thomas' Hospital, London, United Kingdom. METHODS: In this
      prospective single-surgeon standardized-surgical-procedure fellow-eye comparison,
      an AcrySof SN60AT or an AF-1 YA-60BB IOL was randomized to the first eye of 36
      patients and fellow-eye surgery was performed within 4 to 6 weeks. Follow-up was
      at 1, 3, 6, 12, and 24 months. Best distance- corrected logMAR visual acuity was
      measured at 100% and 9% contrast. Contrast sensitivity was measured using the
      Functional Acuity Contrast Test (FACT) on the Optec 3500 instrument (Stereo
      Optical Company, Inc.). Color vision was assessed with the Farnsworth Munsell 100
      hue test. After pupil dilation, digital retroillumination photographs were taken
      and the percentage area of PCO was calculated using POCO software. RESULTS:
      Posterior capsule opacification was significantly greater in the AF-1 YA-60BB
      group than in the AcrySof SN60AT group at all time points (P<.0001), with the
      difference greatest at 24 months. At 24 months, 100% contrast visual acuity was
      significantly better in the AcrySof SN60AT group than in the AF-1 YA-60BB group
      (P = .0313); 9% contrast visual acuity was significantly better in the AcrySof
      SN60AT group from 6 months onward. There was no significant difference between
      groups in color vision or contrast sensitivity. Electron microscopy showed the
      AcrySof SN60AT IOL has a much sharper posterior edge profile. CONCLUSIONS: The
      AcrySof SN60AT IOL had better PCO performance and thus visual performance than
      the AF-1 YA-60BB IOL. This is attributable to the differences in optic edge
      design.

PMID- 18721709
TI  - Comparison of anterior capsule contraction between 5 foldable intraocular lens
      models.
AB  - PURPOSE: To compare anterior capsule contraction in cataract patients having
      implantation of 1 of 5 foldable intraocular lens (IOL) models and evaluate lens
      epithelial cell (LEC) adhesion to each model. SETTING: Department of
      Ophthalmology, Dokkyo Medical University, Tochigi, Japan. METHODS: This study
      comprised 115 patients (126 eyes) without systemic or ocular complications who
      had phacoemulsification with IOL implantation. The eyes were randomly assigned to
      receive 1 of the following IOLs: acrylic MA60BM (Alcon), SA60AT (Alcon), AR40e
      (Advanced Medical Optics), or YA-60BBR (Hoya) or a silicone AQ310NV (Canon). Two
      weeks and 1, 3, and 6 months postoperatively, the anterior capsule opening area
      was measured using an anterior segment analysis system (EAS-1000, Nidek) and the
      percentage of anterior capsule contraction was compared for each postoperative
      period and IOL. Cell adhesion to each IOL type was evaluated using LECs from
      albino rabbits. RESULTS: The mean age of the patients was 73.6 years +/- 5.6
      (SD). Eyes with the AQ310NV and AR40e IOLs had statistically significantly
      greater anterior capsule contraction. The rabbit study showed statistically
      significantly less LEC adhesion on these 2 IOL models. CONCLUSIONS: Anterior
      capsule contraction was significantly greater with the AQ310NV and AR40e IOLs
      than with the other IOLs. Results indicate that cell adhesion to the IOL is an
      important factor in preventing anterior capsule contraction.

PMID- 18721710
TI  - Intraoperative performance and postoperative outcomes of endocapsular ring
      implantation in pediatric eyes.
AB  - PURPOSE: To study the intraoperative performance and postoperative outcomes of
      Cionni modified capsule tension ring (CTR) and intraocular lens (IOL)
      implantation in the capsular bag in pediatric eyes with ectopia lentis. SETTING:
      John A. Moran Eye Center, Salt Lake City, Utah, USA. METHODS: Thirty-five eyes
      (22 children) with ectopia lentis and visually significant cataract that had lens
      aspiration and in-the-bag implantation of single-piece AcrySof IOL and Cionni CTR
      were included. Single- and double-eyelet CTRs were used. The rings were sutured
      to the sclera using 9-0 or 10-0 polypropylene (Prolene) sutures. Preoperative and
      postoperative best corrected visual acuity (BCVA), intraoperative performance,
      IOL centration, and complications were studied. RESULTS: The mean patient age was
      8.2 years +/- 5.1 (SD) and the median follow-up, 28 months. A double-eyelet CTR
      was implanted in 12 eyes and a single-eyelet CTR, in 23 eyes. The mean BCVA at
      the final follow-up (0.37 +/- 0.25 logMAR, 33 eyes) was significantly better than
      preoperatively (0.78 +/- 0.42 logMAR, 28 eyes) (P = .003). At the last
      examination, the BCVA was 20/40 or better in 16 eyes (45.7%). Three eyes (8.5%)
      required resuturing for IOL decentration. Nineteen eyes (54.3%) had a secondary
      procedure for posterior capsule opacification. Other complications included
      anterior capsule opacification (2.85%), cystoid macular edema (5.71%), chronic
      uveitis (5.71%), and vitreous prolapse (2.85%). CONCLUSION: Implantation of the
      Cionni CTR and single-piece AcrySof IOL in the capsular bag in pediatric eyes
      with subluxated lenses was safe and effective and led to a stable IOL with few
      significant complications.

PMID- 18721711
TI  - Comparison of ketorolac 0.4% and bromfenac 0.09% at trough dosing: aqueous drug
      absorption and prostaglandin E2 levels.
AB  - PURPOSE: To compare aqueous drug concentrations and prostaglandin E(2) (PGE(2))
      levels in patients treated with ketorolac 0.4% and bromfenac 0.09% at trough
      dosing. SETTING: Private practice, Wilkes-Barre, Pennsylvania, USA. METHODS: This
      single-center randomized investigator-masked clinical study comprised 56 patients
      having cataract surgery. Patients received 1 drop of ketorolac 0.4% or bromfenac
      0.09% 6 hours and 12 hours preoperatively consistent with on-label dosing
      schedules. Aqueous humor was collected at the start of surgery and analyzed for
      concentrations of ketorolac and bromfenac using a reverse-phase high-performance
      liquid chromatography-mass spectroscopy system and for PGE(2) levels by
      competitive enzyme immunoassay. RESULTS: The mean aqueous PGE(2) level was 204.2
      pg/mL +/- 95.5 (SD) in patients treated with ketorolac 0.4% and 263.7 +/- 90.0
      pg/mL in patients treated with bromfenac 0.09%, (P = .020). The mean aqueous
      concentration of ketorolac and bromfenac at trough dosing was 130.5 +/- 37.8
      ng/mL and 6.2 +/- 3.1 ng/mL, respectively (P = .004). CONCLUSIONS: Higher aqueous
      levels and greater PGE(2) inhibition were observed in cataract surgery patients
      treated with ketorolac 0.4% than in patients treated with bromfenac 0.09% at
      trough dosing. These findings suggest that ketorolac 0.4% administered 4 times a
      day may provide better control of prostaglandin-mediated inflammation than
      bromfenac 0.09% administered twice a day.

PMID- 18721712
TI  - First efficacy and safety study of femtosecond lenticule extraction for the
      correction of myopia: six-month results.
AB  - PURPOSE: To prospectively study the feasibility of femtosecond lenticule
      extraction (FLE), a new method of refractive correction. SETTING: Department of
      Ophthalmology, Philipps University of Marburg and Helios Clinic, Erfurt, Germany.
      METHODS: A flap and a lenticule of intrastromal corneal tissue were
      simultaneously cut with a VisuMax femtosecond laser system. Next, the lenticule
      was manually removed and the flap repositioned. The target refraction in all
      cases was -0.75 diopter (D). RESULTS: All 10 myopic eyes in the initial treatment
      group completed the final 6-month follow-up. The mean patient age was 39 years.
      The mean spherical equivalent (SE) was -4.73 +/- 1.48 (SD) preoperatively and 
      0.33 +/- 0.61 D 6 months postoperatively. Ninety percent of eyes were within +/
      1.00 D and 40% were within +/-0.50 D of the intended correction. No eye lost 2 or
      more Snellen lines. Corneal topography showed large, prolate optical zones.
      Aberrometry showed no significant induction of higher-order aberrations. On a
      standardized questionnaire, all patients said they were very satisfied with the
      results. CONCLUSIONS: Preliminary results indicate that FLEx [corrected] is a
      promising new corneal refractive procedure to correct myopia.

PMID- 18721713
TI  - Intacs implantation using a femtosecond laser for management of keratoconus:
      Comparison of 306 cases in different stages.
AB  - PURPOSE: To evaluate the efficacy of intrastromal ring segment (Intacs, Addition
      Technology, Inc.) implantation and analyze outcomes according to different
      keratoconus stages. SETTING: Kudret Eye Hospital, Ankara, Turkey. METHOD: In this
      retrospective noncomparative case series, 306 keratoconic eyes of 255 patients
      who had Intacs segment implantation were reviewed. Patients were grouped
      according to the Amsler-Krumeich keratoconus classification (stage II, 155 eyes;
      stage III, 83 eyes; stage IV, 68 eyes). The uncorrected visual acuity (UCVA),
      best corrected visual acuity (BCVA), central corneal curvature, spherical and
      cylindrical manifest refractions, and central corneal thickness were analyzed and
      compared according to keratoconus stage. RESULTS: At a mean follow-up of 10.39
      months +/- 5.04 (SD), the BCVA improved in 71.6% of eyes and the UCVA improved in
      75.7% of eyes. The mean keratometry (K) decreased from 50.7 diopters (D) to 47.9
      D (P<.05); the mean manifest spherical refraction, from -6.04 D to -3.09 D
      (P<.05); and the mean manifest cylindrical refraction, from -4.11 D to -3.82 D
      (P>.05). The changes in BCVA and manifest spherical and cylindrical refractions
      were not statistically different between the different keratoconus stages (P
      >.05). There was less change in UCVA and more improvement in the mean K value
      after Intacs treatment in stage IV than in the other stages (P<.05, analysis of
      variance). CONCLUSIONS: Intacs treatment with a femtosecond laser was effective
      for management of keratoconus of all stages. Improvement in UCVA may be less in
      severe keratoconus than in moderate keratoconus.

PMID- 18721714
TI  - Comparison of laser in situ keratomileusis and photorefractive keratectomy
      results: long-term follow-up.
AB  - PURPOSE: To compare the results of photorefractive keratectomy (PRK) and laser in
      situ keratomileusis (LASIK) over a 4-year follow-up. SETTING: Miyata Eye
      Hospital, Miyazaki, Japan. METHODS: This comparative retrospective study
      comprised 22 eyes (22 patients) that had PRK and 18 eyes (18 patients) that had
      LASIK. To be included, the patient had to have completed a 4-year follow-up.
      Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA),
      percentage of eyes within +/-0.5 diopter (D) of the targeted refraction, central
      corneal thickness, and the anterior and posterior corneal elevations were
      compared between the PRK and LASIK groups. RESULTS: The mean UCVA was
      significantly better in the LASIK group than in the PRK group at 6 months (P =
      .0043) and 1 year (P = .0044). At 2 years, there was no significant difference in
      the mean UCVA between the 2 groups. The mean BSCVA was significantly better in
      the LASIK group than in the PRK group at 6 months (P<.0001), 1 year (P<.0001),
      and 2 years (P = .0083). At 3 and 4 years, there was no significant difference in
      the mean BSCVA between the 2 groups. The percentage of eyes within +/-0.5 D of
      the targeted refraction was not significantly different between groups at any
      time. CONCLUSIONS: The superiority of LASIK over PRK in short-term efficacy was
      not retained 4 years after surgery. The main reasons were a myopic shift and a
      decline in UCVA at the last follow-up in the LASIK group.

PMID- 18721715
TI  - Visual outcomes after wavefront-guided laser in situ keratomileusis with and
      without iris registration.
AB  - PURPOSE: To compare the clinical outcomes of wavefront-guided laser in situ
      keratomileusis in eyes in which iris registration was used (IR group) and eyes in
      which iris registration would not engage (no-IR group). SETTING: Shiley Eye
      Center, University of California San Diego, La Jolla, California, USA. METHODS:
      This retrospective analysis comprised 112 eyes of 64 patients who had wavefront
      guided LASIK using the Visx CustomVue S4 IR platform (Advanced Medical Optics)
      for myopia or myopic astigmatism. The safety, efficacy, predictability, and need
      for enhancement at the 3-month follow-up were evaluated and compared between the
      IR group and the no-IR group. RESULTS: By 3 months postoperatively, all eyes in
      the IR group and 93% of eyes in the no-IR group had the same best spectacle
      corrected visual acuity (BSCVA) as preoperatively or had gained 1 to 2 lines of
      BSCVA. No eye in either group lost more than 1 line of BSCVA (P = 0.12). Ninety
      six percent of eyes in the IR group and 93% in the no-IR group were within +/
      0.50 diopter (D) of the postoperative manifest refraction spherical equivalent (P
      = 0.24), and all eyes were within +/-1.00 D of emmetropia. Four eyes in the IR
      group and 11 in the no-IR group required retreatment during the follow-up period
      (P = 0.1). CONCLUSION: The results in the IR group and the no-IR group were
      comparable, with no statistically significant differences in measured outcomes.

PMID- 18721716
TI  - Effect of brimonidine tartrate 0.15% on night-vision difficulty and contrast
      testing after refractive surgery.
AB  - PURPOSE: To evaluate the efficacy of brimonidine tartrate ophthalmic solution
      0.15% in patients with night-vision difficulties after laser refractive surgery.
      SETTING: Center for Refractive Surgery, Walter Reed Army Medical Center,
      Washington, District of Columbia, USA. METHODS: Six patients with significant
      night-vision complaints after refractive surgery were enrolled in this study
      after other treatable causes of night-vision difficulty such as residual
      refractive error and dry eye were excluded. Low-contrast visual acuity (LCVA)
      over a range of contrasts (1.25% to 25%) and small letter contrast sensitivity
      were tested at photopic (100 cd/m(2)) and mesopic (1 cd/m(2)) luminance levels,
      with and without a standard glare source. Testing was performed before
      brimonidine tartrate ophthalmic solution 0.15% was administered. Measurements
      were repeated 1 hour and 1 month after the use of brimonidine tartrate. RESULTS:
      One hour after using brimonidine tartrate 0.15% solution, patients had
      significant improvement in LCVA, LCVA with glare, and contrast sensitivity. After
      1 month of treatment, all 6 patients reported subjective improvement in night
      vision and there was a significant difference in performance in mesopic LCVA and
      mesopic LCVA with glare. The mean pupil size before administration of brimonidine
      tartrate ophthalmic solution 0.15% was 6.44 mm +/- 1.11 (SD). Pupil size 1 hour
      after instillation had decreased to 4.53 +/- 1.27 mm and at 1 month had increased
      to 6.50 +/- 0.94 mm. CONCLUSION: Brimonidine tartrate ophthalmic solution 0.15%
      improved contrast sensitivity and acuity and decreased night-vision difficulty
      for up to 1 month in patients with significant complaints after refractive
      surgery.

PMID- 18721718
TI  - Corneal refractive changes due to short-term eyelid pressure in downward gaze.
AB  - PURPOSE: To assess corneal refractive changes after 15-minute visual tasks and
      their association with eyelid morphology. SETTING: Contact Lens and Visual Optics
      Laboratory, School of Optometry, Queensland University of Technology, Brisbane,
      Queensland, Australia. METHODS: Eighteen young subjects with normal ocular health
      were recruited. Corneal topography was measured with a videokeratoscope before
      and after 4 conditions consisting of 2 downward gaze angles (20 degrees and 40
      degrees) and 2 types of visual tasks (reading and steady fixation). Anterior eye
      photography in downward gaze was used to determine the eyelid angle, tilt, and
      position with respect to the cornea. RESULTS: Corneal refractive power changed
      significantly after the 15-minute downward gaze tasks. The largest mean corneal
      spherocylindrical change was +0.33 -0.30 x 84 after reading in the 40-degree
      downward gaze (4.0 mm corneal diameter). The refractive changes were
      significantly larger after the 40-degree tasks than after the 20-degree tasks
      (P<.001). The changes in refractive root-mean-square error were significant for
      all conditions, except the 20-degree steady fixation task, with 4.0 and 6.0 mm
      analysis diameters (P<.05). Significant correlations were found between some
      aspects of eyelid morphometry and corneal refractive change. CONCLUSIONS: The
      pressure of the eyelids on the cornea in short-term downward gaze resulted in
      optically and clinically relevant corneal changes. Correlation between the
      refractive corneal changes and eyelid parameters suggests that the angle, shape,
      and position of the eyelids influence the nature of the corneal changes. When
      high accuracy is required, refraction should be qualified by the visual tasks
      undertaken before assessment.

PMID- 18721717
TI  - Effect of nepafenac sodium 0.1% on delayed corneal epithelial healing and haze
      after photorefractive keratectomy: retrospective comparative study.
AB  - PURPOSE: To assess delayed epithelialization and corneal haze related to
      nepafenac ophthalmic suspension 0.1% (Nevanac) use after photorefractive
      keratectomy (PRK). SETTING: Private practice, Beverly Hills, California, USA.
      METHODS: This retrospective comparative chart review comprised 69 eyes (44
      patients) that were divided into 2 treatment groups that were not statistically
      significantly different in age or preoperative spherical equivalent. The
      nepafenac group consisted of 34 eyes (22 patients) that received nepafenac 0.1%,
      moxifloxacin, and fluorometholone postoperatively. The non-nepafenac group
      included 35 eyes (22 patients) that received moxifloxacin and fluorometholone
      only. Patients were seen between 1 day and 5 days postoperatively for evaluation
      of epithelial healing and haze formation. Delayed epithelialization was defined
      as healing after day 5. All patients were followed for haze formation for a
      minimum of 3 months. RESULTS: Statistical analysis showed no difference between
      the nepafenac and non-nepafenac groups in delayed epithelialization (P = .61, chi
      square test). Neither group had significant corneal haze. CONCLUSION: Nepafenac
      did not appear to delay corneal epithelial healing or contribute to haze
      formation after PRK.

PMID- 18721719
TI  - In vivo analysis of wound architecture in 700 microm microphakonit cataract
      surgery.
AB  - PURPOSE: To analyze the clear corneal wound architecture in 700 microm cataract
      surgery (microphakonit) using anterior segment optical coherence tomography (AS
      OCT). SETTING: Dr Agarwal's Eye Hospital and Eye Research Centre, Chennai, India.
      METHODS: Wound architecture was analyzed by AS-OCT 30 minutes after surgery and
      1, 3, and 7 days postoperatively in 12 eyes (11 patients) that had microphakonit
      surgery. Five eyes had microphakonit with a 700 microm phaco tip with no
      intraocular lens (IOL) implantation, and 7 eyes had foldable IOL implantation
      after the main port was extended with a 2.8 mm keratome. RESULTS: Twenty-four
      clear corneal wounds, which included the main port and the side port, were
      studied. The mean endothelial misalignment in the microphakonit wound was 0.085
      mm +/- 0.09 (SD) immediately postoperatively, 0.057 +/- 0.07 mm at 1 day, 0.020
      +/- 0.04 mm at 3 days, and 0.0 mm at 7 days. The mean coaptation loss was 0.030
      +/- 0.06 mm immediately postoperatively, 0.029 +/- 0.04 mm at 1 day, and 0.029 +/
      0.04 mm at 3 days. There was a significant positive correlation between the
      change in stromal hydration and coaptation loss in the 17 wounds without
      extension; 82.3% of wounds at 3 days and 100% at 7 days had complete endothelial
      alignment. CONCLUSION: Although there was no significant difference in
      endothelial misalignment, coaptation loss, or amount of stromal hydration between
      microphakonit wounds without and wounds with a 2.8 mm keratome extension, wound
      healing and resolution of coaptation loss or endothelial realignment occurred
      earlier in wounds without extension.

PMID- 18721721
TI  - Unilateral axial length elongation with chronic traumatic cataracts in young
      Kenyans.
AB  - PURPOSE: To assess whether unilateral axial elongation in chronic traumatic
      cataract is associated with the time interval from trauma to surgery. SETTING:
      PCEA Kikuyu Hospital Eye Unit, Nairobi, Kenya. METHODS: This retrospective cohort
      study analyzed patients with traumatic cataract operated on between 1998 and
      2007. Study patients (n = 13) had a delay from trauma to surgery of more than 1
      year and an interocular axial length (AL) difference greater than 1.0 mm.
      Randomly selected age-matched control patients (n = 14) had less than 1 year
      delay between trauma and surgery. The correlation between interocular AL
      difference and surgical delay was calculated in each group. RESULTS: The median
      interval from trauma to surgical treatment in study patients was 8 years (range 1
      to 27 years). Study patients had a significantly higher median interocular AL
      difference (3.09 mm; interquartile range [IQR] 2.45 to 4.13 mm) than control
      patients (0.24 mm; IQR 0.15 to 0.30 mm) (P = .000). The length of delay from
      trauma to surgical treatment did not correlate strongly with the interocular AL
      difference in study or control patients (R(2) = 0.0143 and R(2) = 0.1697,
      respectively). CONCLUSIONS: Unilateral AL elongation may occur in young adults
      with chronic traumatic cataract. Delay of more than 1 year from trauma to surgery
      was associated with axial elongation, although the degree of elongation did not
      correlate with duration of delay. Surgeons are advised to implant lower-power
      intraocular lenses in such patients based on biometry readings to avoid
      postoperative refractive surprises.

PMID- 18721720
TI  - Optical coherence tomography of clear corneal incisions for cataract surgery.
AB  - PURPOSE: To study the architecture of clear corneal incisions for
      phacoemulsification cataract surgery using optical coherence tomography (OCT).
      SETTING: Doheny Eye Institute and Department of Ophthalmology, Keck School of
      Medicine of the University of Southern California, Los Angeles, California, USA.
      METHODS: This prospective study comprised 20 eyes of 20 patients 1 month after
      cataract surgery performed by 1 of 2 experienced surgeons. Temporal clear corneal
      single-plane incisions were made with 3.0 mm metal keratomes. Each eye was
      scanned before and 1 month after surgery with a prototype high-speed anterior
      segment OCT system (Carl Zeiss Meditec, Inc.). The OCT scans were repeated 3
      times during the same visit. The length of the corneal incision, thickness of the
      cornea, and position of the incision (distance from external wound edge to
      scleral spur) were measured using a computer caliper. The angle of the incision
      relative to the corneal surface was then calculated. RESULTS: The mean corneal
      incision length was 1.81 mm +/- 0.27 (SD), the mean corneal thickness at the
      incision was 747 +/- 67 microm, and the mean distance between the incision and
      the scleral spur was 1.46 +/- 0.24 mm. The mean angle of the incision was 26.8 +/
      5.5 degrees. The measurements were repeatable to within +/-0.072 mm (pooled
      standard deviation) for the incision length, +/-11 microm for the corneal
      thickness, and +/-0.042 mm for the position of the incision. CONCLUSIONS: Optical
      coherence tomography allowed excellent evaluation of corneal incisions in
      cataract surgery postoperatively. Measurements of wound dimensions using OCT were
      highly repeatable.

PMID- 18721722
TI  - Clinical magnification and residual refraction after implantation of a double
      intraocular lens system in patients with macular degeneration.
AB  - PURPOSE: To evaluate the efficacy of a standard double intraocular lens (IOL)
      system (IOL-Vip) in patients with low vision and central scotoma due to macular
      degeneration and assess the predictability of the residual refraction and
      magnification. SETTING: Ophthalmology Department, Hospital General Universitario,
      Valencia, Spain. METHODS: This interventional prospective noncomparative case
      series comprised 13 consecutive surgical procedures in 10 patients with central
      scotoma. Follow-up was 12 months. Evaluation included the difference between
      preoperative and postoperative best corrected visual acuity (BCVA), refraction,
      position of the IOLs, endothelial cell density, and occurrence of postoperative
      complications. Residual refraction and eye magnification were calculated using a
      theory developed in a previous study, and the values were compared with the
      clinical results. RESULTS: The mean BCVA was 1.37 logMAR preoperatively and 0.68
      logMAR 1 year postoperatively. The mean best corrected clinical gain was 44%.
      There was no statistically significant difference between the clinically
      evaluated and theoretically calculated residual refractions (P = .17). No
      intraoperative or postoperative complications occurred. CONCLUSIONS: Implantation
      of the double IOL system improved BCVA in patients with low vision due to
      advanced maculopathy. The results were best in myopic patients (long eyes);
      patients with hyperopia (short eyes) had high residual refraction. The
      postoperative clinical gain and residual refraction were predictable, showing the
      feasibility of implanting a customized double IOL.

PMID- 18721723
TI  - Donor tissue preparation for Descemet membrane endothelial keratoplasty.
AB  - PURPOSE: To evaluate a technique for preparing a donor Descemet membrane carrying
      autologous endothelium for transplantation in Descemet membrane endothelial
      keratoplasty (DMEK). SETTING: Netherlands Institute for Innovative Ocular
      Surgery, Rotterdam, The Netherlands. METHODS: A 9.5 mm diameter DM carrying
      autologous endothelium was stripped from 10 corneoscleral rims that had been
      organ cultured for 1 week. The endothelial cell density (ECD) was evaluated with
      light microscopy before and immediately after DM was stripped and during 4
      additional weeks of organ culture. RESULTS: The mean ECD was 2701 cells/mm(2) +/-
      302 (SD) before and 2719 +/- 322 cells/mm(2) immediately after DM was stripped
      and declined from 2604 +/- 352 cells/mm(2) after 1 week to 2190 +/- 768
      cells/mm(2) after an additional 4 weeks of organ culture (n = 10). Typical
      "endothelial streaks," ie, linear cellular disruptions observed immediately after
      DM was stripped, showed complete regeneration after the second culture period.
      CONCLUSIONS: Descemet grafts for transplantation in DMEK procedures can be
      surgically prepared from organ-cultured corneal rims and stored for an additional
      3 weeks with acceptable endothelial cell loss. Because the donor tissue can be
      dissected directly from organ-cultured corneoscleral rims, donor preparation for
      DMEK can be readily accessible to most corneal surgeons.

PMID- 18721724
TI  - Complications of foldable intraocular lenses requiring explantation or secondary
      intervention--2007 survey update.
AB  - The tenth annual survey of complications associated with foldable intraocular
      lenses (IOLs) requiring explantation or secondary intervention was sent to
      members of the American Society of Cataract and Refractive Surgery and the
      European Society of Cataract and Refractive Surgeons. Preoperative data about
      visual acuity, patient signs and symptoms, and complications requiring IOL
      removal were evaluated. Complications were then tabulated for each of the
      following major foldable IOL groups: 1-piece (plate) silicone, 1-piece
      hydrophobic acrylic with haptics, 3-piece silicone, 3-piece hydrophobic acrylic,
      3-piece hydrophilic acrylic (hydrogel), 3-piece unknown, multifocal acrylic, and
      multifocal silicone. One hundred forty-two surveys were returned for evaluation.
      Dislocation/decentration, incorrect IOL power, glare/optical aberrations, and IOL
      calcification were the most common reasons for removing foldable IOLs. Good
      surgical technique, accurate IOL power measurements, and high manufacturing
      standards for foldable IOL materials and designs are the most important factors
      in preventing complications.

PMID- 18721725
TI  - Acute macular hole and retinal detachment in highly myopic eyes after
      neodymium:YAG laser capsulotomy.
AB  - We report 2 cases of acute onset of macular hole and retinal detachment (MHRD) in
      highly myopic eyes after uneventful neodymium:YAG (Nd:YAG) laser posterior
      capsulotomy. Case 1 was a 76-year-old highly myopic woman who had decreased
      vision 4 days after Nd:YAG capsulotomy. Macular hole and retinal detachment were
      detected, and vitrectomy was performed. Case 2 was a 62-year-old highly myopic
      woman who reported visual loss 1 week after Nd:YAG capsulotomy. Macular hole and
      retinal detachment were detected, and vitrectomy was performed and the retina
      reattached. The developmental mechanisms of MHRD after Nd:YAG capsulotomy are
      discussed.

PMID- 18721726
TI  - Pigmentary glaucoma secondary to in-the-bag intraocular lens implantation.
AB  - After uneventful phacoemulsification and in-the-bag implantation of an AcrySof
      SA60AT (Alcon) intraocular lens (IOL), a 52-year-old black man developed
      pigmentary glaucoma. Slitlamp examination, anterior segment optical coherence
      tomography, and ultrasound biomicroscopy showed that the posterior surface of the
      iris was being rubbed by the inferior haptic of the IOL, which was in the bag but
      deformed. Filtering surgery was needed to control the intraocular pressure. This
      type of IOL can cause IOL-induced pigmentary glaucoma.

PMID- 18721727
TI  - Capsulorhexis phimosis after bimanual microphacoemulsification and in-the-bag
      implantation of the Akreos MI60 intraocular lens.
AB  - An 80-year-old woman with corticonuclear cataract had cataract extraction by
      bimanual microphacoemulsification and in-the-bag implantation of the Akreos MI60
      (Bausch & Lomb) intraocular lens (IOL). After 6 months, a complete capsulorhexis
      phimosis developed and surgery was performed to open and reduce the phimosis,
      with complete functional recovery. In the fellow pseudophakic eye, an acrylic
      hydrophobic Acri. Smart 48S (Acri.Tec) IOL had been implanted without
      complications. We conclude that a capsulorhexis phimosis may occur a few months
      after uneventful cataract surgery and in-the-bag implantation of the Akreos MI60
      IOL.

PMID- 18721728
TI  - Delayed-onset isolated central Descemet membrane blister detachment following
      phacoemulsification.
AB  - We report 2 patients who developed delayed-onset isolated central Descemet
      membrane (DM) blister-like detachment following phacoemulsification. The
      detachments were not associated with a DM tear or inadvertent injection of fluid
      under DM, and no fluid tracks from the periphery were present. When the
      detachments failed to resolve spontaneously over several months, intracameral air
      or C(3)F(8) gas was injected. In 1 patient, a therapeutic paracentral puncture in
      DM was also performed to facilitate escape of the entrapped fluid. Although a
      small residual detachment (confirmed by optical coherence tomography) remained in
      both cases, the visual acuity improved to 20/25 in 1 patient and 20/30 in the
      other. We think these unique focal detachments in DM may be associated with an
      underlying preexisting weakness in the DM attachment to the stroma.

PMID- 18721729
TI  - Unusual pattern of glistening formation on a 3-piece hydrophobic acrylic
      intraocular lens.
AB  - A 3-piece hydrophobic acrylic intraocular lens (IOL) was explanted from the left
      eye of a 68-year-old patient 26 days after implantation because of glistenings
      that impaired fundus visualization. The effect of the glistenings on the
      patient's visual function was unknown because of retinal issues. The fluid-filled
      vacuoles within the IOL optic were different from those described in clinical and
      experimental studies. They were initially observed 4 days after surgery and were
      very large. The glistening formation was reproduced experimentally by immersing
      the explanted IOL in balanced salt solution at 37 degrees C and analyzing the IOL
      at room temperature for up to 2 weeks. An IOL of the same design was used as a
      control. Although both IOLs were subjected to the same laboratory conditions,
      gross and light microscopic analyses confirmed that the pattern of the glistening
      formation differed between them. Analyses of the explanted IOL and the control
      IOL under differential scanning calorimetry, as well as by attenuated total
      reflection Fourier transform infrared spectroscopy, revealed slight differences
      between the IOLs.

PMID- 18721730
TI  - The grape: an appropriate model for continuous curvilinear capsulorhexis.

PMID- 18721731
TI  - Safe and easy way to release sticking haptic of a single-piece AcrySof
      intraocular lens.

PMID- 18721732
TI  - Iatrogenic retinal detachment due to cannula slippage despite use of luer-lock
      syringe system.

PMID- 18721733
TI  - Vitamin D deficiency and associated factors in hemodialysis patients.
AB  - BACKGROUND: Vitamin D deficiency is prevalent in the general elderly population,
      and is related to an increased risk of osteoporosis, fractures, and
      cardiovascular calcification. Only limited data and no guidelines are available
      on vitamin D deficiency in hemodialysis patients. OBJECTIVE: We aimed to assess
      the frequency of, and factors associated with, 25(OH) vitamin D deficiency in
      hemodialysis patients in a French dialysis center. DESIGN: In March 2006, we
      studied all prevalent hemodialysis patients who had not received native vitamin D
      supplements in the recent past. According to the Kidney Disease Outcomes and
      Quality Initiative guidelines, patients were assigned to the following 3 groups:
      group 1, with a sufficient vitamin D serum level (>75 nmol/L); group 2, with an
      insufficient level (25 to 75 nmol/L); and group 3, with severe deficiency (<25
      nmol/L). Patients' characteristics and biochemical findings were compared between
      patients of groups 1 and 3. RESULTS: Of 253 patients, 11% patients were in group
      1; 47% were in group 2; and 42% were in group 3. The proportions of female and
      diabetes patients were 42% and 34%, respectively. The mean (+/- SD) age of all
      patients was 66.7 +/- 14 years, and the mean duration of dialysis was 62 +/- 74
      months, with a mean schedule of 3 x 6.5 hours and administration of a 1.5 mmol/L
      calcium dialysate. Concomitant treatment included alfacalcidol (66% of patients)
      and sevelamer (34% of patients) as a standard phosphate binder. Group 3 patients
      had a lower dialysis vintage (53 +/- 66 vs. 73 +/- 85 months, P < .05), a higher
      number of diabetes patients (45% vs. 21%, P < .05), a higher number of female
      patients (53% vs. 28%, P < .05), and a higher level of intact parathyroid hormone
      (260 +/- 227 vs. 213 +/- 153 pg/mL, P < .05) than group 1 patients. No
      relationship was found between vitamin D storage levels and bone markers, serum
      calcium, phosphorus, albumin, body mass index, normalized protein catabolic rate,
      radiologic vascular calcification score, and hip bone mineral density. In
      multivariate logistic regression analyses, no factors were significantly
      associated with vitamin D deficiency. CONCLUSIONS: Calcidiol deficiency was
      highly prevalent in a French dialysis population. The associated factors mainly
      included female sex, diabetes, shorter dialysis duration, and higher intact
      parathyroid hormone level. Although there are no guidelines for the therapy of
      patients with chronic kidney disease at stage 5, the usefulness of vitamin D
      supplementation may be assessed by considering its potential direct action, the
      need for providing fuel for renal and extrarenal calcitriol production in
      particular, and the numerous potential favorable effects on health.

PMID- 18721734
TI  - Vitamin D binding protein and the need for vitamin D in hemodialysis patients.
AB  - OBJECTIVE: Vitamin D binding protein (DBP) is a polymorphic serum protein with a
      predominant role in a spectrum of biological activities. Chronic renal failure is
      characterized by deficient vitamin D metabolism. The present study investigates
      the impact of DBP polymorphism on the need for vitamin D in hemodialysis
      patients. DESIGN: This was a retrospective study. SETTING: This study included
      hemodialysis patients from the Renal Unit of Ghent University Hospital (Ghent,
      Belgium) and the Algemeen Stedelijk Ziekenhuis Geraardsbergen Hospital
      (Geraardsbergen, Belgium). METHODS: One hundred and ninety-one hemodialysis
      patients and 211 healthy subjects were recruited from the hemodialysis database.
      The DBP phenotypes were determined by polyacrylamide gel electrophoresis. Serum
      DBP, parathyroid hormone, 25-hydroxyvitamin D(3), 1,25-dihydroxyvitamin D(3),
      calcium, albumin, and phosphate were measured. Information regarding the intake
      of vitamin D analogues was collected. RESULTS: The phenotypic distributions of
      DBP were in agreement with Hardy-Weinberg equilibrium. Comparing allele
      frequencies of the two groups, there was an increased proportion of the DBP 2
      allele in hemodialysis patients (P < .05). The median serum DBP concentration was
      lowest in the DBP 2-2 group. The need for oral vitamin D differed significantly
      (P < .01) between DBP phenotypes, and was greatest in DBP 2-2. CONCLUSIONS: The
      present study demonstrates an altered DBP allele frequency in hemodialysis
      patients, compared with the general population. More importantly, vitamin D
      intake differs depending on the DBP polymorphism, and is greatest for end-stage
      renal disease patients with a DBP 2-2 phenotype. Therefore, vitamin D treatment
      deserves more careful monitoring among DBP 2-2 patients with end-stage renal
      disease.

PMID- 18721735
TI  - Vitamin D status of chronic kidney disease patients living in a sunny country.
AB  - BACKGROUND: Vitamin D nutritional status has been poorly investigated in chronic
      kidney disease (CKD) patients, especially those inhabiting a subtropical area
      where the sunlight incidence is abundant all year. OBJECTIVE: The purpose of this
      study was to evaluate the status of vitamin D and to analyze the relationship of
      circulating 25-hydroxyvitamin D [25(OH)D] with other serum parameters of mineral
      metabolism in patients with CKD not yet on dialysis. DESIGN: This cross-sectional
      study enrolled 144 nondiabetic CKD patients not yet receiving dialysis (stages 2
      to 5 of CKD). Fasting blood samples were obtained for measurements of 25
      hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], intact
      parathyroid hormone, phosphorus, and calcium. RESULTS: In the entire sample, the
      serum concentration of 25(OH) was 34.3 +/- 18.3 ng/mL (+/-SD unless otherwise
      noted). A deficiency of vitamin D, i.e., 25(OH)D <15 ng/mL, was found in only one
      patient. Fifty-seven patients (39.6%) were considered vitamin D-insufficient (16
      to 30 ng/mL). The vitamin D-insufficient group contained more females, a higher
      degree of proteinuria, and a lower serum concentration of 1,25(OH)(2)D. In
      multiple regression analysis, 25(OH)D was associated positively with
      1,25(OH)(2)D, serum calcium, and proteinuria, whereas 1,25(OH)(2)D was associated
      only with 25(OH)D and phosphorus. The variables associated with intact
      parathormone were serum phosphorus and creatinine clearance, but not 1,25(OH)(2)D
      or 25(OH)D. CONCLUSION: Despite an elevated prevalence of vitamin D
      insufficiency, the serum concentration of 25(OH)D was, on average, higher than
      that found in patients inhabiting higher-latitude regions. This higher serum
      concentration may have contributed to the differences found in the relationship
      between vitamin D metabolites and other serum markers of mineral metabolism in
      our CKD patients.

PMID- 18721736
TI  - Comparison of dietary compliance and dietary knowledge between older and younger
      Korean hemodialysis patients.
AB  - OBJECTIVE: The numbers of older hemodialysis patients (OHPs) are increasing very
      rapidly worldwide, but few studies have focused on the compliance of OHPs. This
      study compared the compliance with, and the knowledge of, dietary restriction
      regimens between OHPs and younger hemodialysis patients (YHPs). Mortality was
      also compared between these two groups. PATIENTS AND SETTING: A total of 160
      patients who were registered at the Asan Medical Center (Seoul, Korea)
      participated in the study, 64 of whom were classified as OHPs (age >or=65 years),
      and 96 as YHPs (age <65 years). MAIN OUTCOME MEASURES: Data were collected
      between September 2003 and February 2004. General characteristics and dietary
      knowledge of potassium, phosphorus, and sodium and fluid restrictions were
      assessed by personal interview. Dietary compliance was determined by measuring
      serum levels of these nutrients and interdialytic weight gain. Subjective global
      assessments were used to evaluate nutritional status. Both OHPs and YHPs were
      followed until May 2007 for mortality analysis. The data were analyzed with
      descriptive statistics, Student's t test, chi(2) test, and Spearman correlation
      using the SPSS statistical package (SPSS, Inc., Chicago, IL). RESULTS: The OHPs
      had a lower appetite, lower physical activity, and lower educational level
      compared with the YHPs. Dietary compliance with phosphorus restriction and with
      sodium and fluid restriction was higher in the OHPs than in the YHPs (P < .01 and
      P < .05, respectively), whereas compliance with potassium restriction did not
      differ between groups. The knowledge scores concerning potassium (P < .05) and
      phosphorus (P < .01) restriction diets were lower in OHPs than in YHPs, whereas
      no differences were found for knowledge scores concerning sodium and fluid
      restriction diets. Mortality was higher in the OHPs than in the YHPs (P < .001).
      The OHPs with higher mortality had higher dietary compliance with sodium and
      fluid restriction (r = 0.248, P < .05), and lower nutritional status (r = -0.342,
      P < .05). CONCLUSIONS: The OHPs were generally less knowledgeable and more
      compliant, and had a lower appetite and a higher mortality than the YHPs.
      Therefore, the current application of the same dietary education to both OHPs and
      YHPs may be problematic. Instead, developing age-specific strategies to increase
      dietary knowledge and nutritional intake is urgently needed to increase the
      survival rate of Korean hemodialysis patients.

PMID- 18721737
TI  - Association between body mass index and body fat in chronic kidney disease stages
      3 to 5, hemodialysis, and peritoneal dialysis patients.
AB  - OBJECTIVE: Chronic kidney disease (CKD) patients may present with altered body
      composition. Body mass index (BMI) is a simple method for evaluating body fat
      mass (FM) in the general population. In CKD patients, there are few reports
      demonstrating the association between BMI and body composition. Our objective was
      to investigate the reliability of BMI as an indicator of FM in patients with CKD
      stages 3 to 5. METHODS: Seventy-eight nondiabetic CKD patients (aged 48, SD +/-
      12 years; 45% male) and 30 healthy control subjects (aged 46, SD +/- 12 years;
      40% male), matched for age and sex, were evaluated. Chronic kidney disease
      patients were divided, according to K/DOQI guidelines, into 27 subjects at stages
      3 to 4 (mean glomerular filtration rate of 43 +/- 12 mL/minute; age, 52 +/- 10
      years), and 51 at stage 5: 25 in hemodialysis (HD) (aged 45, SD +/- 12 years; 44%
      male), and 26 in peritoneal dialysis (PD) (aged 49, SD +/- 13 years; 42% male).
      Body mass index was calculated as weight/height(2), and body composition was
      evaluated through dual-energy x-ray absorptiometry. RESULTS: There was no
      difference in median BMI (kg/m(2)) among healthy control subjects (24.8; range,
      19.2-34.1), CKD stages 3 to 4 (26.4; range, 20.4-37.6), HD patients (24.5; range,
      19.4-35.7), and PD patients (24.5; range, 20.2-37.7; P > .05). Likewise, no
      significant difference was verified in median body FM (kg) among control subjects
      (18.8; range, 9.2-36.5), CKD stages 3 to 4 (21.2; range, 11.6-37.9), HD patients
      (17.1; range, 4.8-38.9), and PD patients (20.1; range, 6.5-41.5; P > .05).
      Moreover, a positive and significant correlation was found between BMI and FM
      (kg) in CKD stages 3 to 4 (Rho = 0.67, P = .0002), in HD patients (Rho = 0.67, P
      = .0002), in PD patients (Rho = 0.79, P < .0001), and in control subjects (Rho =
      0.79, P < .0001). Although BMI and lean body mass (in kg) was significantly
      correlated in CKD stages 3 to 4 (Rho = 0.58, P = .001) and healthy control
      subjects (Rho = 0.30, P = .007), no significant correlation was found in HD
      patients (Rho = 0.19, P = .34) and in PD patients (Rho = 0.17, P = .38).
      CONCLUSIONS: Body composition did not differ in patients with CKD stages 3 to 5,
      and between dialysis modalities. Although BMI was strongly and significantly
      correlated with body FM in CKD patients at stages 3 to 5, lean body mass was not.
      These findings suggest that BMI is a reliable indicator of body FM in this CKD
      population.

PMID- 18721738
TI  - Validation of a composite scoring scheme in the diagnosis of folate deficiency in
      a pediatric and adolescent dialysis cohort.
AB  - BACKGROUND: Laboratory indices are often poorly diagnostic of folate deficiency
      (FD). Compared with iron depletion in hemodialysis (HD) populations, the impact
      of FD is less appreciated. The composite scoring of hematologic indices of FD may
      facilitate a prompt and accurate diagnosis, and enhance operational research on
      folic acid therapy. OBJECTIVE: Our objectives were to (1) validate composite
      scores of folate diagnostic indices, and (2) determine the reliability index of
      the diagnostic tool. METHODS: A cohort of 30 subjects, with a mean age of 16 (SD
      +/- 3.2 years), on HD and erythropoietin (EPO) for a minimum of 3 months was
      studied. After a baseline hematologic assessment, routine folates were
      administered for 6 months. Composite FD scores (FDS) of baseline mean corpuscular
      volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin
      concentration (MCHC), random distribution width (RDW), and hemoglobin were
      determined. Validation and reliability statistics were then analyzed, using the
      quantitative change in red blood cell folate/plasma homocysteine, or EPO
      requirement after 6 months of folate use, as diagnostic criteria. RESULTS: The
      mean FDS for FD and non-FD subsets were 3.0 +/- 1.3 and 1.4 +/- 0.9, respectively
      (analysis of variance; P = .0001). The correlation coefficient, r(2), between FD
      total and FDS was 0.61 (P = .001), and the coefficient between 2 (weekly) values
      of RDW, MCV, MCH, and MCHC was >0.84 (P = .0001). Scoring tools derived from the
      first (P = .002) and second (P = .01) halves of the laboratory indices remained
      discriminatory for the FD and non-FD groups. Baseline serum folate is poorly
      specific for FD, whereas FD score >or=3 had sensitivity, specificity, and
      positive and negative predictive values close to 90%. CONCLUSIONS: Composite
      scoring of erythrocyte indices was predictive of the FD diagnosis, as defined by
      the quantitative response of red blood cell folate, homocysteine, and EPO dose to
      folate therapeutic intervention. The diagnostic items yielded a high reliability
      coefficient. The FDS scheme is a potential tool for the diagnosis and
      surveillance of FD, particularly in at-risk populations (e.g., dialysis
      subjects).

PMID- 18721739
TI  - Long-term effect of a chicken-based diet versus enalapril on albuminuria in type
      2 diabetic patients with microalbuminuria.
AB  - OBJECTIVE: In short-term studies, the replacement of red meat in the diet with
      chicken reduced the urinary albumin excretion rate (UAER) and improved lipid
      profile in type 2 diabetic patients with diabetic nephropathy. The present study
      sought to assess these effects over a long-term period, comparing the effects of
      a chicken-based diet (CD) versus enalapril on renal function and lipid profile in
      microalbuminuric type 2 diabetic patients. DESIGN: This was a randomized, open
      label, controlled clinical trial with a follow-up of 1 year. SETTING: The trial
      involved outpatients with type 2 diabetes attending a clinic of the Division of
      Endocrinology at a tertiary-care hospital. PATIENTS: Twenty-eight
      microalbuminuric patients completed the study and were evaluated. INTERVENTIONS:
      Patients were randomized to an experimental diet (CD plus active placebo) or to
      treatment with enalapril (10 mg/day plus usual diet). MAIN OUTCOME MEASURES: The
      main outcome measure was UAER (according to immunoturbidimetry). Blood pressure,
      anthropometric indices, and compliance were also evaluated monthly. The
      glomerular filtration rate ((51)Cr-EDTA), and lipid, glycemic, and nutritional
      indices, were measured at baseline and quarterly. RESULTS: The UAER was reduced
      after CD (n = 13; from 62.8 [range, 38.4 to 125.1] to 49.1 [range, 6.2 to 146.5]
      microg/min; P < .001) and after enalapril (n = 15; from 55.8 [range, 22.6 to
      194.3] to 23.1 [range, 4.0 to 104.9] microg/min; P < .001), and this was already
      significant at month 4. The reduction in UAER after CD (32%; 95% confidence
      interval, 6.7% to 57.6%) and after enalapril treatment (44.7%; 95% confidence
      interval, 28.3% to 61.1%; P = .366) were not significantly different.
      CONCLUSIONS: The CD and the angiotensin-converting enzyme inhibitor enalapril
      promoted a similar reduction of UAER in patients with type 2 diabetes and
      microalbuminuria in a 12-month follow-up period.

PMID- 18721740
TI  - Feedback inhibition of cholesterol biosynthesis by dietary cholesterol in
      experimental chronic renal failure.
AB  - OBJECTIVE: Enhanced liver cholesterol synthesis is present in experimental
      chronic renal failure (CRF), even though cholesterol concentrations in blood and
      liver are increased, suggesting that CRF results in disturbed cholesterolegenesis
      feedback regulation. DESIGN: This study sought to elucidate whether dietary
      cholesterol exerts inhibitory effects on liver cholesterologenesis in CRF rats.
      METHODS: Male Wistar rats were used. Experimental CRF was achieved by a 5/6
      nephrectomy model. Cholesterologenesis was measured (1) in vivo by tritiated
      water incorporation into cholesterol, and (2) in vitro (using liver slices) by
      [(14)C]-acetate and [(3)H]-mevalonate incorporation into cholesterol. In
      addition, the mRNA abundance of 3-hydroxy-3-methylglutaryl-CoA reductase, a rate
      limiting enzyme in cholesterologenesis pathway, as well as its activity, was
      determined. Finally, the mRNA level of liver sterol regulatory element-binding
      protein-2, a nuclear transcription factor engaged in intracellular cholesterol
      homeostasis, was measured. RESULTS: Experimental CRF was associated with
      significantly increased concentrations of serum and liver cholesterol. In vitro
      and in vivo cholesterologenesis was enhanced in CRF rats. A cholesterol-enriched
      diet resulted in a significant decrease in (1) in vivo and in vitro cholesterol
      synthesis, (2) 3-hydroxy-3-methylglutaryl-CoA reductase gene expression, and (3)
      the level of liver sterol regulatory element-binding protein-2 mRNA in CRF rats.
      CONCLUSIONS: Despite elevated plasma and liver cholesterol concentrations,
      cholesterologenesis is increased in CRF rats. It is, however, inhibited by
      dietary cholesterol. These results suggest that a feedback inhibition of
      cholesterologenesis by dietary cholesterol is preserved in experimental CRF.

PMID- 18721741
TI  - Estimated net acid excretion inversely correlates with urine pH in vegans, lacto
      ovo vegetarians, and omnivores.
AB  - OBJECTIVE: Diet affects urine pH and acid-base balance. Both excess acid/alkaline
      ash (EAA) and estimated net acid excretion (NAE) calculations have been used to
      estimate the effects of diet on urine pH. This study's goal was to determine if
      free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic
      urine, and to assess the ability of EAA and estimated NAE calculations to predict
      urine pH. DESIGN: This study used a cross-sectional design. SETTING AND
      PARTICIPANTS: This study assessed urine samples of 10 vegan, 16 lacto-ovo
      vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six
      3-day food records from each dietary group were analyzed for EAA content and
      estimated NAE, and correlations with measured urine pH were calculated. RESULTS:
      The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto
      ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P =
      .013). Calculated EAA values were not significantly different among the three
      groups, whereas mean estimated NAE values were significantly different: 17.3 +/-
      14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6
      +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average
      deattenuated correlation between urine pH and EAA was 0.333; this value was 
      0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 -
      0.014 NAE (P = .02, r = -0.54). CONCLUSIONS: Habitual diet and estimated NAE
      calculations indicate the probable ranking of urine pH by dietary groups, and may
      be used to determine the likely acid-base status of an individual; EAA
      calculations were not predictive of urine pH.

PMID- 18721742
TI  - Fast food, phosphorus-containing additives, and the renal diet.
AB  - OBJECTIVE: Fast food is commonly consumed by hemodialysis patients, but many menu
      items are not compatible with renal diets because of their sodium, potassium, or
      phosphorus content. Moreover, the phosphorus content of fast foods is difficult
      for patients to estimate, because phosphorus-containing additives are commonly
      added to many fast foods. We sought to determine how many fast-food entrees and
      side dishes are compatible with renal diets. METHODS: We examined nutrition-facts
      labels and ingredient lists provided by 15 fast-food chains. Each entree and side
      dish was first assessed according to traditional criteria (limited sodium,
      potassium, and naturally occurring phosphorus content), and then according to the
      presence of a phosphorus -containing additive. RESULTS: Of 804 total entrees
      across all restaurants, 415 (52%) were acceptable according to traditional
      criteria, but only 128 (16%) were also free of phosphorus-containing additives.
      Of 163 total side dishes, 37 (23%) were acceptable according to traditional
      criteria, and 27 (17%) were also free of phosphorus-containing additives. There
      were no acceptable entrees at 3 chains, and no acceptable side dishes at 5
      chains. CONCLUSION: Only a small proportion of fast-food entrees and side dishes
      are compatible with renal diets. The widespread use of phosphorus-containing
      additives is a major impediment to the availability of acceptable fast-food
      choices for hemodialysis patients. We recommend limiting the use of phosphorus
      containing additives, and including phosphorus content in nutrition-facts labels.

PMID- 18721743
TI  - Conditions for coverage released: implications for nephrology dietitians.

PMID- 18721744
TI  - Seeking clues to transplantation tolerance.

PMID- 18721745
TI  - Interactome of ErbB4 unveiled.
AB  - MacBeath and colleagues (Kaushansky et al., 2008) use a protein array technology
      to find binding partners of ErbB4 in a genome-wide and quantitative fashion,
      shedding new light on how ErbB4 initiates cellular signaling events and why ErbB4
      is not a potent oncogene.

PMID- 18721746
TI  - GFP family: structural insights into spectral tuning.
AB  - Proteins homologous to green fluorescent protein (GFP) span most of the visible
      spectrum, offering indispensable tools for live cell imaging. Structural
      transformations, such as posttranslational autocatalytic and photo-induced
      modifications, chromophore isomerization, and rearrangements in its environment
      underlie the unique capacity of these proteins to tune their own optical
      characteristics. A better understanding of optical self-tuning mechanisms would
      assist in the engineering of more precisely adapted variants and in expanding the
      palette of GFP-like proteins to the near-infrared region. The latest advances in
      this field shed light upon multiple features of protein posttranslational
      chemistry, and establish some important basic principles about the interplay of
      structure and spectral properties in the GFP family.

PMID- 18721748
TI  - DKxanthene biosynthesis--understanding the basis for diversity-oriented synthesis
      in myxobacterial secondary metabolism.
AB  - The DKxanthenes are a family of yellow pigments which play a critical role in
      myxobacterial development. Thirteen unique structures from Myxococcus xanthus
      DK1622 differ in the length of their characteristic polyene functionality, as
      well as the extent of methyl branching. We aimed to understand the mechanistic
      basis for this "molecular promiscuity" by analyzing the gene cluster in DK1622,
      and comparing it to the DKxanthene biosynthetic locus in a second myxobacterium,
      Stigmatella aurantiaca DW4/3-1, which produces a more limited range of compounds.
      While the core biosynthetic machinery is highly conserved, M. xanthus contains a
      putative asparagine hydroxylase function which is not present in S. aurantiaca.
      This observation accounts, in part, for the significantly larger metabolite
      family in M. xanthus. Detailed analysis of the encoded hybrid polyketide synthase
      (PKS)-nonribosomal peptide synthetase (NRPS) assembly line provides direct
      evidence for the mechanism underlying the variable polyene length and the
      observed pattern of methyl functionalities.

PMID- 18721747
TI  - Cloning, expression, and biochemical characterization of Streptomyces
      rubellomurinus genes required for biosynthesis of antimalarial compound FR900098.
AB  - The antibiotics fosmidomycin and FR900098 are members of a unique class of
      phosphonic acid natural products that inhibit the nonmevalonate pathway for
      isoprenoid biosynthesis. Both are potent antibacterial and antimalarial
      compounds, but despite their efficacy, little is known regarding their
      biosynthesis. Here we report the identification of the Streptomyces
      rubellomurinus genes required for the biosynthesis of FR900098. Expression of
      these genes in Streptomyces lividans results in production of FR900098,
      demonstrating their role in synthesis of the antibiotic. Analysis of the putative
      gene products suggests that FR900098 is synthesized by metabolic reactions
      analogous to portions of the tricarboxylic acid cycle. These data greatly expand
      our knowledge of phosphonate biosynthesis and enable efforts to overproduce this
      highly useful therapeutic agent.

PMID- 18721749
TI  - Loop grafting of Bacillus subtilis lipase A: inversion of enantioselectivity.
AB  - Lipases are successfully applied in enantioselective biocatalysis. Most lipases
      contain a lid domain controlling access to the active site, but Bacillus subtilis
      Lipase A (LipA) is a notable exception: its active site is solvent exposed. To
      improve the enantioselectivity of LipA in the kinetic resolution of 1,2-O
      isopropylidene-sn-glycerol (IPG) esters, we replaced a loop near the active-site
      entrance by longer loops originating from Fusarium solani cutinase and
      Penicillium purpurogenum acetylxylan esterase, thereby aiming to increase the
      interaction surface for the substrate. The resulting loop hybrids showed
      enantioselectivities inverted toward the desired enantiomer of IPG. The
      acetylxylan esterase-derived variant showed an inversion in enantiomeric excess
      (ee) from -12.9% to +6.0%, whereas the cutinase-derived variant was improved to
      an ee of +26.5%. The enantioselectivity of the cutinase-derived variant was
      further improved by directed evolution to an ee of +57.4%.

PMID- 18721750
TI  - Deciphering deazapurine biosynthesis: pathway for pyrrolopyrimidine nucleosides
      toyocamycin and sangivamycin.
AB  - Pyrrolopyrimidine nucleosides analogs, collectively referred to as deazapurines,
      are an important class of structurally diverse compounds found in a wide variety
      of biological niches. In this report, a cluster of genes from Streptomyces
      rimosus (ATCC 14673) involved in production of the deazapurine antibiotics
      sangivamycin and toyocamycin was identified. The cluster includes toyocamycin
      nitrile hydratase, an enzyme that catalyzes the conversion of toyocamycin to
      sangivamycin. In addition to this rare nitrile hydratase, the cluster encodes a
      GTP cyclohydrolase I, linking the biosynthesis of deazapurines to folate
      biosynthesis, and a set of purine salvage/biosynthesis genes, which presumably
      convert the guanine moiety from GTP to the adenine-like deazapurine base found in
      toyocamycin and sangivamycin. The gene cluster presented here could potentially
      serve as a model to allow identification of deazapurine biosynthetic pathways in
      other bacterial species.

PMID- 18721751
TI  - Chemical dissection of the link between streptozotocin, O-GlcNAc, and pancreatic
      cell death.
AB  - Streptozotocin is a natural product that selectively kills insulin-secreting beta
      cells, and is widely used to generate mouse models of diabetes or treat
      pancreatic tumors. Several studies suggest that streptozotocin toxicity stems
      from its N-nitrosourea moiety releasing nitric oxide and possessing DNA
      alkylating activity. However, it has also been proposed that streptozotocin
      induces apoptosis by inhibiting O-GlcNAcase, an enzyme that, together with O
      GlcNAc transferase, is important for dynamic intracellular protein O
      glycosylation. We have used galacto-streptozotocin to chemically dissect the link
      between O-GlcNAcase inhibition and apoptosis. Using X-ray crystallography,
      enzymology, and cell biological studies on an insulinoma cell line, we show that,
      whereas streptozotocin competitively inhibits O-GlcNAcase and induces apoptosis,
      its galacto-configured derivative no longer inhibits O-GlcNAcase, yet still
      induces apoptosis. This supports a general chemical poison mode of action for
      streptozotocin, suggesting the need for using more specific inhibitors to study
      protein O-GlcNAcylation.

PMID- 18721752
TI  - System-wide investigation of ErbB4 reveals 19 sites of Tyr phosphorylation that
      are unusually selective in their recruitment properties.
AB  - The first three members of the ErbB family of receptor tyrosine kinases activate
      a wide variety of signaling pathways and are frequently misregulated in cancer.
      Much less is known about ErbB4. Here we use tandem mass spectrometry to identify
      19 sites of tyrosine phosphorylation on ErbB4, and protein microarrays to
      quantify biophysical interactions between these sites and virtually every SH2 and
      PTB domain encoded in the human genome. Our unbiased approach highlighted several
      previously unrecognized interactions and led to the finding that ErbB4 can
      recruit and activate STAT1. At a systems level, we found that ErbB4 is much more
      selective than the other ErbB receptors. This suggests that ErbB4 may enable
      ErbB2 and ErbB3 to signal independently of EGFR under normal conditions, and
      provides a possible explanation for the protective properties of ErbB4 in cancer.

PMID- 18721753
TI  - Enzymatic macrolactonization in the presence of DNA leading to triostin A
      analogs.
AB  - Excised thioesterase domains are versatile catalysts for macrocyclization.
      However, thioesterase-catalyzed cyclization is often precluded due to the
      occurrence of hydrolysis and product inhibition. To circumvent these obstacles,
      we devised an unprecedented strategy: coincubation with DNA to capture the cyclic
      products possessing DNA-binding properties. In experiments involving echinomycin
      thioesterase-catalyzed macrolactonization leading to the cyclic triostin A analog
      TANDEM, we found that the addition of DNA drastically improved the yield of
      TANDEM (19% --> 67%), with a complete reversal of the cyclization:hydrolysis
      ratio (1:2 --> 18:1). Furthermore, the applicability of this protocol was
      demonstrated for a variety of substrates. The results described herein provide
      insight into the mechanism of echinomycin thioesterase-catalyzed conversions and
      also pave the way for chemoenzymatic synthesis of the quinoxaline antibiotics and
      their analogs.

PMID- 18721754
TI  - Development of pyrrole-imidazole polyamide for specific regulation of human
      aurora kinase-A and -B gene expression.
AB  - Pyrrole-imidazole polyamide (PIP) is a nuclease-resistant novel compound that
      inhibits gene expression through binding to the minor groove of DNA. Human aurora
      kinase-A (AURKA) and -B (AURKB) are important regulators in mitosis during the
      cell cycle. In this study, two specific PIPs (PIP-A and PIP-B) targeting AURKA
      and AURKB promoter regions were designed and synthesized, and their biological
      effects were investigated by several in vitro assays. PIP-A and PIP-B
      significantly inhibited the promoter activities, mRNA expression, and protein
      levels of AURKA and AURKB, respectively, in a concentration-dependent manner.
      Moreover, 1:1 combination treatment with both PIPs demonstrated prominent
      antiproliferative synergy (CI value [ED(50)] = 0.256) to HeLa cells as a result
      of inducing apoptosis-mediated severe catastrophe of cell-cycle progression. The
      novel synthesized PIP-A and PIP-B are potent and specific gene-silencing agents
      for AURKA and AURKB.

PMID- 18721756
TI  - Covalent inhibitors of human monoacylglycerol lipase: ligand-assisted
      characterization of the catalytic site by mass spectrometry and mutational
      analysis.
AB  - The active site of recombinant hexa-histidine-tagged human monoacylglycerol
      lipase (hMGL) is characterized by mass spectrometry using the inhibitors 5
      ((biphenyl-4-yl)methyl)-N,N-dimethyl-2H-tetrazole-2-carboxamide (AM6701), and N
      arachidonylmaleimide (NAM) as probes. Carbamylation of Ser(129) by AM6701 in the
      putative hMGL catalytic triad demonstrates this residue's essential role in
      catalysis. Partial NAM alkylation of hMGL cysteine residues 215 and/or 249 was
      sufficient to achieve approximately 80% enzyme inhibition. Although Cys(215)
      and/or Cys(249) mutations to alanine(s) did not affect hMGL hydrolytic activity
      as compared with nonmutated hMGL, the C215A displayed heightened NAM sensitivity,
      whereas the C249A evidenced reduced NAM sensitivity. These data conclusively
      demonstrate a sulfhydryl-based mechanism for NAM inhibition of hMGL in which
      Cys(249) is of paramount importance. Identification of amino acids critical to
      the catalytic activity and pharmacological modulation of hMGL informs the design
      of selective MGL inhibitors as potential drugs.

PMID- 18721755
TI  - Biochemical and structural insights of the early glycosylation steps in
      calicheamicin biosynthesis.
AB  - The enediyne antibiotic calicheamicin (CLM) gamma(1)(I) is a prominent antitumor
      agent that is targeted to DNA by a novel aryltetrasaccharide comprised of an
      aromatic unit and four unusual carbohydrates. Herein we report the heterologous
      expression and the biochemical characterization of the two "internal"
      glycosyltransferases CalG3 and CalG2 and the structural elucidation of an
      enediyne glycosyltransferase (CalG3). In conjunction with the previous
      characterization of the "external" CLM GTs CalG1 and CalG4, this study completes
      the functional assignment of all four CLM GTs, extends the utility of enediyne GT
      catalyzed reaction reversibility, and presents conclusive evidence of a
      sequential glycosylation pathway in CLM biosynthesis. This work also reveals the
      common GT-B structural fold can now be extended to include enediyne GTs.

PMID- 18721757
TI  - Amide N-glycosylation by Asm25, an N-glycosyltransferase of ansamitocins.
AB  - Ansamitocins are potent antitumor maytansinoids produced by Actinosynnema
      pretiosum. Their biosynthesis involves the initial assembly of a macrolactam
      polyketide, followed by a series of postpolyketide synthase (PKS) modifications.
      Three ansamitocin glycosides were isolated from A. pretiosum and fully
      characterized structurally as novel ansamitocin derivatives, carrying a beta-D
      glucosyl group attached to the macrolactam amide nitrogen in place of the N
      methyl group. By gene inactivation and complementation, asm25 was identified as
      the N-glycosyltransferase gene responsible for the macrolactam amide N
      glycosylation of ansamitocins. Soluble, enzymatically active Asm25 protein was
      obtained from asm25-expressing E. coli by solubilization from inclusion bodies.
      Its optimal reaction conditions, including temperature, pH, metal ion
      requirement, and Km/Kcat, were determined. Asm25 also showed broad substrate
      specificity toward other ansamycins and synthetic indolin-2-ones. To the best of
      our knowledge, this represents the first in vitro characterization of a purified
      antibiotic N-glycosyltransferase.

PMID- 18721758
TI  - Allogeneic hematopoietic cell transplantation for adult Philadelphia-positive
      acute lymphoblastic leukemia in the era of tyrosine kinase inhibitors.
AB  - Allogeneic hematopoietic cell transplantation in first complete remission (CR1)
      is considered the standard of care, and the only established therapy that offers
      a possibility of cure for patients with Philadelphia-positive acute lymphoblastic
      leukemia (Ph+ ALL). Unfortunately, a number of patients, with suitable HLA
      matched donors, are unable to receive an allograft because they fail to respond,
      or relapse shortly after induction chemotherapy. Incorporating imatinib during
      the induction/consolidation phase is facilitating a higher number of potentially
      curative allografts by improving both remission rates and/or the durability of
      responses in patients with Ph+ ALL. Imatinib and other tyrosine kinase inhibitors
      are also improving outcomes in elderly patients with Ph+ ALL, ineligible for
      allografting, when combined with glucocorticoids, and/or conventional
      chemotherapy. The addition of imatinib or other tyrosine kinase inhibitors to the
      therapeutic armamentarium of Ph+ ALL is reshaping the treatment algorithm and
      improving prognosis of this dreadful disease.

PMID- 18721759
TI  - Th2 cell therapy of established acute graft-versus-host disease requires IL-4 and
      IL-10 and is abrogated by IL-2 or host-type antigen-presenting cells.
AB  - Delayed donor Th2 cell infusion permits a graft-versus-tumor (GVT) effect to
      occur with subsequent amelioration of established graft-versus-host disease
      (GVHD). Relative to GVHD controls (B6-into-BALB/c model), recipients of delayed
      Th2 cells (day 14 post-BMT) had increased survival (3/3 experiments [exp]; each
      exp P < .0001) and reduced GVHD by histology analysis 5 days post-Th2 infusion
      without increased tumor burden (3 of 3 exp; each exp P < or = .02). Th2 cell
      mediated amelioration of GVHD was associated with greatly reduced allospecific
      IFN-gamma secretion, in vivo augmentation of allospecific IL-4 and IL-10
      secretion, and reduction in donor CD8(+) T cell number post-BMT (3 of 3 exp; each
      comparison, P < or = .003). To better understand the molecular mechanism of this
      GVHD therapy, Th2 cells were generated from wild-type (WT), IL-4 deficient (KO),
      or IL-10 KO donors: remarkably, recipients of IL-4 or IL-10 KO Th2 cells had no
      survival advantage, no improvement in GVHD by histology, no reduction in CD8(+) T
      cell expansion post-BMT, and no in vivo shift toward type II cytokines. We
      reasoned that IL-2 and alloantigen availability may be limiting factors for Th2
      cell therapy, and as such, evaluated whether coadministration of IL-2 or
      coinfusion of host-type antigen-presenting cells (APC) might intensify the anti
      GVHD effect. However, contrary to these hypotheses, concomitant IL-2 therapy or
      APC administration fully abrogated the Th2 cell-mediated survival advantage and
      histology-defined GVHD reduction, reduced Th2 cell expansion in vivo while
      promoting CD8(+) T cell expansion from cells originating from the initial
      allograft, and impaired type II polarization in vivo. In conclusion, Th2 cell
      therapy can rapidly ameliorate severe GVHD via IL-4 and IL-10 mediated
      mechanisms, and potentially, via IL-2 consumption and APC modulation mechanisms.

PMID- 18721760
TI  - CpG-induced myeloid CD11b+Gr-1+ cells efficiently suppress T cell-mediated
      immunoreactivity and graft-versus-host disease in a murine model of allogeneic
      cell therapy.
AB  - Transplantation of mismatched allografts in irradiated recipients results in
      lethal graft- versus-host disease (GVHD). In our study, pretransplantation donor
      treatment with CpG, administered either alone or emulsified in incomplete
      Freund's adjuvant, efficiently prevented GVHD in sublethally irradiated
      recipients of haploidentical (H-2(b) into H-2(b/d)) and fully mismatched (H-2(b)
      into H-2(d)) allografts. CpG treatment of donor mice caused an accumulation of
      double-positive CD11bGr-1 cells in their blood and spleens, whereas treatment
      with CpG+IFA resulted in an even greater accumulation of these cells. Isolated
      CD11b(+) cells from the spleens of CpG+IFA-treated mice efficiently suppressed
      alloreactivity in vitro (> 92%), as determined by co-culturing these cells in
      mixed lymphocyte reactions. After CpG+IFA treatment, a T cell-depleted fraction
      enriched with CD11b(+)Gr-1(+) cells, acting as myeloid suppressor cells, was able
      to efficiently prevent GVHD induced by naive T cells in the sublethally
      irradiated recipients: 20/21 mice remained GVHD-free survivors for more than 200
      days. Splenocytes from CpG+IFA-treated mice displayed enhanced interleukin (IL)
      6, IL-10, and interferon-gamma production, reduced T cell allogeneic and
      mitogenic responses, as well as failure of T cells to induce GVHD. In summary,
      CpG treatment led to impaired T cell function, enriched myeloid suppressor cells
      and regulatory cytokine production, which together appear to suppress
      alloreactivity and protect against the development of GVHD. We hypothesize that
      similar immunoregulatory effects could be applied experimentally in a clinical
      setting when inhibition of alloreactivity is required in recipients of stem cell
      allografts.

PMID- 18721761
TI  - Does the hematopoietic cell transplantation specific comorbidity index predict
      transplant outcomes? A validation study in a large cohort of umbilical cord blood
      and matched related donor transplants.
AB  - The hematopoietic cell transplantation specific comorbidity index (HCT-CI) has
      been recently proposed to predict the probability of nonrelapse mortality (NRM)
      and overall survival (OS) in allogeneic HCT recipients while taking into account
      any pretransplant comorbidity. We tested the validity of the HCT-CI in a cohort
      of 373 adult HCT recipients (184 matched-related donor and 189 unrelated
      umbilical cord blood) who received a myeloablative (N = 150) or nonmyeloablative
      (N = 223) conditioning regimen. HCT-CI scores of 0, 1, 2, and > or =3 were
      present in 58 (16%), 56 (15%), 64 (17%), and 195 (52%) patients, respectively.
      Pulmonary conditions were the most common comorbidity. Cumulative incidence of
      NRM at 2 years was 10%, 20%, 24%, and 28% for HCT-CI scores of 0, 1, 2, and > or
      =3, respectively (P = .01). The corresponding probability of OS at 2 years was
      72%, 67%, 51%, and 48%, respectively (P < .01). On multivariate analyses adjusted
      for recipient age, disease risk, donor source, and conditioning regimen
      intensity, the relative risks for NRM for HCT-CI scores of 1, 2, and > or =3
      (compared to a score of 0) were 2.0 (95% confidence intervals, 0.8-5.3), 2.6 (1.0
      6.7), and 3.2 (1.4-7.4), respectively. The risks for overall mortality were 1.2
      (0.6-2.1), 2.0 (1.1-3.4), and 2.1 (1.3-3.3), respectively. In subgroup analyses,
      the HCT-CI score did not consistently predict NRM and OS among different donor
      sources and conditioning regimens. The HCT-CI, although a useful tool for
      capturing pretransplant comorbidity and risk-assessment, needs to be further
      validated prior to adopting it for routine clinical use.

PMID- 18721763
TI  - Pulmonary function changes in experimental graft-versus-host disease of the lung.
AB  - Pulmonary graft-versus-host disease (p-GVHD) is a serious complication after
      allogeneic stem cell transplantation (allo-SCT) of high morbidity and high
      mortality. We characterized breathing patterns and pulmonary function changes in
      correlation to lung histopathology and survival by using a well-established
      murine model of p-GVHD. Lethally irradiated B6D2F1 mice received SCT from either
      syngeneic B6D2F1 or allogeneic C57BL/6 animals. Within 6 weeks, severe p-GVHD
      developed in allogeneic recipients characterized by progressive interstitial,
      alveolar, peribronchial, and periluminal inflammatory cell infiltration, whereas
      in syngeneic recipients lung histology remained normal. Allogeneic recipients
      demonstrated decreased minute ventilation (MV), reduced peak inspiratory and
      expiratory flow rates as early as 1 week after SCT. In addition, allo-SCT
      resulted in restrictive pulmonary function changes as early as 7 days after
      transplantation and in progressive airflow obstruction within 6 weeks. Decreased
      breathing abilities and pulmonary function changes of allogeneic recipients were
      associated with increased mortality and the severity of acute graft-versus-host
      disease (aGVHD). These findings show that p-GVHD can be characterized by changes
      in pulmonary function and functional respiratory insufficiency. Furthermore, our
      data strengthen the understanding, that the lung is a critical target organ of
      aGVHD.

PMID- 18721762
TI  - Outcomes following HSCT using fludarabine, busulfan, and thymoglobulin: a matched
      comparison to allogeneic transplants conditioned with busulfan and
      cyclophosphamide.
AB  - We have reported a lower incidence of acute graft-versus-host disease (aGVHD)
      with a novel conditioning regimen using low-dose rabbit antithymocyte globulin
      (ATG; Thymoglobulin [TG]) with fludarabine and intravenous busulfan (FluBuTG). To
      assess further this single-center experience, we performed a retrospective
      matched-pair analysis comparing outcomes of adult patients transplanted using the
      FluBuTG conditioning regimen with matched controls from patients reported to the
      CIBMTR receiving a first allogeneic hematopoietic stem cell transplant (HCT)
      after standard oral busulfan and cyclophosphamide (BuCy). One hundred twenty
      cases and 215 matched controls were available for comparison. Patients receiving
      FluBuTG had significantly less treatment related mortality (TRM; 12% versus 34%,
      P < .001) and grades II-IV aGVHD (15% versus 34%, P < .001) compared to BuCy
      patients. The risk of relapse was higher in the FluBuTG patients (42% versus 20%,
      P < .001). The risks of chronic GVHD (cGVHD) and disease free survival (DFS) were
      similar in the cases and controls. These results suggest that the novel regimen
      FluBuTG decreases the risk of aGVHD and TRM after HLA-identical sibling HSCT, but
      is associated with an increased risk of relapse, resulting in similar DFS.
      Whether these conditioning regimens may be more suitable for specific patient
      populations based on relapse risk requires testing in prospective randomized
      trials.

PMID- 18721764
TI  - Long-term follow-up of a phase I/II randomized, placebo-controlled trial of
      palifermin to prevent graft-versus-host disease (GVHD) after related donor
      allogeneic hematopoietic cell transplantation (HCT).
AB  - We previously conducted a randomized, double-blind, placebo-controlled study
      conducted from 2000 to 2003 of palifermin, a recombinant human keratinocyte
      growth factor, dosed from 240 microg/kg to 720 microg/kg, in 100 allogeneic
      hematopoietic stem cell transplantation (HCT) recipients. Treatment with
      palifermin showed beneficial effects on mucositis, but no significant effect on
      engraftment, acute graft-versus-host disease (GVHD), or early survival. In
      addition to the effect of palifermin on mucosa, other pleotrophic effects,
      including more rapid immune reconstitution, have been seen in experimental
      transplant models. Therefore, we investigated whether with longer follow-up we
      could detect additional differences between the palifermin-treated and placebo
      cohorts. We found no differences in CMV or invasive fungal infections, chronic
      GVHD, or long-term survival between cohorts. We conclude that the benefits of
      palifermin appear primarily to be limited to ameliorating mucotoxicity when given
      to allogeneic HCT recipients.

PMID- 18721766
TI  - Umbilical cord mesenchymal stem cells increase expansion of cord blood natural
      killer cells.
AB  - Natural killer (NK) cell-mediated cytotoxicity can control leukemia relapse while
      protecting patients from graft-versus-host disease (GVHD) after allogeneic stem
      cell transplant. Cord blood (CB) is rich in NK cell progenitors with similar
      properties of proliferation and cytotoxicity as adult blood NK cells. Hence, it
      is attractive to expand and potentially utilize these cells for adoptive
      immunotherapy. In this study, CB mononuclear cells were CD3-depleted by
      immunomagnetic microbead selection to remove T cells. This CD3(dep) CB-MNC
      fraction was then plated for ex vivo expansion, with or without a feeder layer of
      irradiated umbilical cord mesenchymal stem cells (UC-MSC), with or without
      cytokines that have been shown to be critical for NK expansion: IL-2, IL-15, IL
      3, and FLT-3L. At an average of 2 weeks of culture, there was significantly
      higher expansion (64.7 +/- 8.4-fold) of CD56(+)/CD3(-) NK cells in the presence
      of the UC-MSC feeder layer and cytokines compared to controls (no increase with
      feeder layer only and 6.4 +/- 1.5-fold increase with cytokines only, P < .05).
      Contact between CD3(dep) CB-MNC cells and UC-MSC augmented NK expansion. The
      combination of all 4 cytokines was superior to IL-2 alone or 2 cytokines
      combinations: mean 64.7 +/- 8.4-fold expansion with 4 cytokines combination
      versus IL-2 alone, IL-2 + FLT-3L, IL-2 + IL-15 or IL-2 + IL-3 (12.2 +/- 2.0, 14.4
      +/- 2.4, 10.4 +/- 4.1, 25.2 +/- 8.1 respectively). We also observed that only
      fresh CD3(dep) CB-MNC preparations could be expanded reliably, whereas frozen and
      thawed CD3(dep) CB-MNC cells did not expand consistently (mean fold increase 6.5
      +/- 3.2). Cytotoxicity of expanded NK cells was compared with NK cells from fresh
      and overnight IL-2 activated CD3(dep) CB-MNC. Whereas fresh cells displayed no
      discernible killing, strong cytotoxicity against K562, Raji, REH, and SUP-B15
      cells lines was noted after overnight activation in IL-2. Cytotoxicity of
      expanded NK cells against Raji, REH, and SUP-B15 was lower, which, however,
      correlated with a predominant expansion of CD56(+)/CD16(-) cells known to have
      less cytolytic activity than CD56(+)/CD16(+). To test the transfection efficiency
      in NK cells, fresh or expanded CD3(dep) CB-MNC cells were electroporated with
      either DNA or mRNA constructs for GFP. DNA had a low transfection efficiency
      (<10%), whereas the one for mRNA reached 52%, but at the cost of significant cell
      death. Our results suggest that CB NK cell progenitors can be expanded to obtain
      large numbers by using an irradiated feeder of UC-MSC. They maintain an elevated
      cytotoxic profile, and may be genetically manipulated-all characteristics that
      make them suitable for cellular therapies.

PMID- 18721767
TI  - Utility of comorbidity assessment in predicting transplantation-related toxicity
      following autologous hematopoietic stem cell transplantation for multiple
      myeloma.
AB  - Patients with coexisting medical problems may suffer increased toxicity and
      reduced quality of life after autologous hematopoietic stem cell transplantation
      (HSCT). The benefit of high-dose therapy for some patients with multiple myeloma
      (MM) is debatable. Decision tools that aid in identifying those patients with MM
      most suited for autologous HSCT may avoid the risk of excess toxicity. An
      objective assessment of comorbidities was performed in 126 patients with MM
      undergoing autologous HSCT using the Charlson comorbidity index (CCI), the
      hematopoietic cell transplantation comorbidity index (HCT-CI), and a modified
      pretransplantation assessment of mortality (mPAM) to determine the strength of
      association with increased transplantation-related toxicity and increased length
      of hospital stay (LOS). Any comorbidity scored using the CCI or HCT-CI (score >
      0) was associated with an increased number of organ systems with serious toxicity
      (at least grade 2 toxicity using the Seattle criteria), an increased total sum of
      toxicity grades for all organs, and prolonged LOS. An mPAM score > or = 24 was
      associated with increased LOS. When considering autologous HSCT for a patient
      with MM, assessment of comorbidities using the CCI or HCT-CI may assist in
      predicting the risk of transplantation-related toxicity as an adjunct to
      physician judgment and patient preference.

PMID- 18721765
TI  - Response to pneumococcal (PNCRM7) and haemophilus influenzae conjugate vaccines
      (HIB) in pediatric and adult recipients of an allogeneic hematopoietic cell
      transplantation (alloHCT).
AB  - Young children and allogeneic hematopoietic cell transplantation (HCT) recipients
      respond poorly to polysaccharide antigens, rendering them susceptible to severe
      infections because of encapsulated bacteria. This study evaluated the responses
      of 127 HCT patients, median age 23.0 years, vaccinated with PNCRM7 and
      Haemophilus influenzae (HIB) conjugate, 2 conjugate vaccines highly immunogenic
      in healthy children. Median time to vaccination was 1.1 years after HCT. Sixty
      two percent of patients responded to PNCRM7 (45 of 51 children, 34 of 76 adults,
      P < .001). Overall response to HIB was 86%, including 77% of PNCRM7
      nonresponders. Although PNCRM7 response was adversely affected by older age (P <
      .001), individuals > or =50 years old responded significantly better if
      vaccinated following acquisition of specific minimal milestones of immune
      competence, CD4 >200/microL, IgG >500 mg/dL, PHA within 60% lower limit of normal
      (11 of 19 versus 0 of 8, P < .006). A similar trend was observed in patients with
      limited chronic graft-versus-host disease (cGVHD). In all patients, higher levels
      of circulating CD4(+)CD45RA cells correlated with improved PNCRM7 response. These
      data demonstrate that PNCRM7 is immunogenic in allogeneic HCT patients, including
      older adults, but suggest that vaccination at fixed intervals after HCT,
      irrespective of immune competence, may limit its effectiveness. Prospective,
      multicenter trials assessing the best strategy to administer this vaccine and its
      impact on pneumococcal infections following transplantation are warranted.

PMID- 18721768
TI  - Impact of mobilization and remobilization strategies on achieving sufficient stem
      cell yields for autologous transplantation.
AB  - The purpose of this article was to examine historic institutional autologous stem
      cell mobilization practices and evaluate factors influencing mobilization failure
      and kinetics. In this retrospective study we analyzed clinical records of 1834
      patients who underwent stem cell mobilization for autologous transplantation from
      November 1995 to October 2006 at the Washington University in St. Louis.
      Successful mobilization was defined as collection of > or =2 x 10(6) CD34(+)
      cells/kg. From 1834 consecutive patients, 1040 met our inclusion criteria (502
      non-Hodgkin's lymphoma [NHL], 137 Hodgkin's lymphoma, and 401 multiple myeloma
      [MM]). A total of 976 patients received granulocyte colony-stimulating factor (G
      CSF) and 64 received G-CSF plus chemotherapy (G/C) for the initial mobilization.
      Although the median CD34(+) cell yield was higher in G/C group than in G-CSF
      alone group, the failure rates were similar: 18.8% and 18.6%, respectively.
      Overall, 53% of patients collected > or =2 x 10(6) CD34(+) cells/kg during the
      first apheresis with either mobilization regimen. Regardless of mobilization
      regimen used, MM patients had the highest total CD34(+) cell yield and required
      less aphereses to collect > or =2 x 10(6) CD34(+) cells/kg. Mobilized,
      preapheresis, peripheral blood CD34(+) count correlated with first day apheresis
      yield (r = .877, P < .001) and 20 cells/microL was the minimum threshold needed
      for a successful day 1 collection. For the remobilization analysis we included
      patients from the whole database. A total of 269 of 1834 patients underwent
      remobilization using G/C, G-CSF, and/or GM-CSF, and G-CSF plus plerixafor. Only
      23% of remobilized patients achieved > or =2 x 10(6) CD34(+) cells/kg and 29.7%
      failed to pool sufficient number of stem cells from both collections. Patients
      receiving G-CSF plus plerixafor had lowest failure rates, P = .03. NHL patients
      remobilized with G-CSF who waited > or =25 days before remobilization had lower
      CD34(+) cell yield than those who waited < or =16 days, P = .023. Current
      mobilization regimens are associated with a substantial failure rate irrespective
      of underlying disease. Patients who fail initial mobilization are more likely to
      fail remobilization. These findings suggest that there is a need for more
      effective first-line mobilization agents.

PMID- 18721769
TI  - Unrelated cord blood transplantation for severe aplastic anemia.
AB  - In the present study we evaluated the feasibility of unrelated cord blood
      transplantation (UCBT) in patients with severe aplastic anemia (SAA). The outcome
      of 31 SAA patients (median age 28; range: 0.9-72.3 years old) who received UCBT
      was analyzed. The cumulative incidences of the neutrophil and platelet recovery
      after UCBT were 54.8 and 72.2%, respectively (95% confidence interval [CI] =
      36.0%-70.3% and 51.3%-85.3%, respectively). The cumulative incidences of grade >
      or =II acute and chronic graft-versus-host disease (aGVHD, cGVHD) were 17.1% (95%
      CI = 6.2%-32.8%) and 19.7% (95% CI = 6.2%-38.8%), respectively. Currently, 13
      patients are alive, having survived for 33.7 months (median; range: 6-77 months)
      after UCBT. The probability of overall survival (OS) at 2 years was 41.1% (95% CI
      = 23.8%-57.7%). A conditioning regimen that included low-dose total body
      irradiation (TBI) (2-5 Gy), fludarabine, and cyclophosphamide resulted in a
      favorable OS (80%; 95% CI = 20.4%-96.9%). This result suggests that UCBT using
      the optimal conditioning regimen can be a salvage treatment for patients without
      a suitable bone marrow donor and warrants evaluation in further prospective
      studies.

PMID- 18721770
TI  - HLAMatchmaker-defined triplet matching is not associated with better survival
      rates of patients with class I HLA allele mismatched hematopoietic cell
      transplants from unrelated donors.
AB  - This report addresses the concept that permissible HLA mismatching, that is,
      mismatches that do not generate an allogeneic response, in hematopoietic stem
      cell transplantation (HCT) can be determined with structural similarity of
      polymorphic regions. We have applied the triplet version of a structural
      algorithm called HLAMatchmaker, which considers short sequences involving
      polymorphic amino acid residues on the molecular surface as key elements of
      immunogenic epitopes. The triplet matching effect was analyzed in a National
      Marrow Donor Program dataset consisting of 744 unrelated hematopoietic cell
      transplantation cases with 1 HLA-A, -B, or -C mismatch and 1690 fully HLA-A, -B, 
      C, -DR, or -DQ allele matched cases. In multivariate models adjusting for other
      significant clinical risk factors, the degree of triplet mismatching did not
      significantly correlate with patient survival, engraftment, or acute graft-versus
      host disease (aGVHD). Other structurally based strategies should be pursued to
      identify permissible HLA mismatches in HCT.

PMID- 18721771
TI  - Increased risk of cervical dysplasia in long-term survivors of allogeneic stem
      cell transplantation--implications for screening and HPV vaccination.
AB  - As more women survive allogeneic stem cell transplantation (SCT), the development
      of genital human papilloma virus (HPV)-related squamous intraepithelial lesions
      (SIL) warrants study. Thirty-five of 38 females followed prospectively long-term
      after SCT for hematological malignancies (median: 7 years posttransplant) were
      adults and had cervical cytology testing. Acute graft-versus-host-disease (aGVHD)
      occurred in 9 and chronic (cGVHD) in 34 patients. Six (17%) continued receiving
      systemic immunosuppressive therapy (IST) for cGVHD >3 years after SCT. Of 15
      (43%) with abnormal cytology, 12 (34%) patients had HPV-related SIL (median time
      to SIL 51 months, range: 22-108) including high-grade SIL in 7 (20%). Patients
      requiring continued IST had the highest risk (odds ratio [OR] 4.6, 95% confidence
      interval [CI] 1.1-16.4; P = .019). This high incidence of SIL in long-term SCT
      survivors underscores the importance of gynecologic assessment after
      transplantation, especially in those requiring IST. This may portend an increased
      risk of genital or other HPV-related malignancies.

PMID- 18721772
TI  - low body mass index is an independent risk factor for transplant-associated
      microangiopathy following total-body irradiation-based conditioning regimens.

PMID- 18721773
TI  - Introduction: 20th anniversary of the NMDP.

PMID- 18721774
TI  - The national marrow donor program 20 years of unrelated donor hematopoietic cell
      transplantation.
AB  - In the 20 years since the National Marrow Donor Program (NMDP) facilitated the
      first unrelated donor transplant, the organization has grown to include almost 7
      million donors, and has facilitated over 30,000 transplants on 6 continents. This
      remarkable accomplishment has been facilitated by the efforts of over 600
      employees, and an extensive international network including 171 transplant
      centers, 73 donor centers, 24 cord blood banks, 97 bone marrow collection
      centers, 91 apheresis centers, 26 HLA typing laboratories, and 26 Cooperative
      Registries. In this article, we review the history of the NMDP, and cite the
      major trends in patient demographics, graft sources, and conditioning regimens
      over the last 20 years.

PMID- 18721775
TI  - Twenty years of unrelated donor hematopoietic cell transplantation for adult
      recipients facilitated by the National Marrow Donor Program.
AB  - For more than 20 years the National Marrow Donor Program has facilitated
      unrelated donor hematopoietic cell transplants for adult recipients. In this time
      period, the volunteer donor pool has expanded to nearly 12 million adult donors
      worldwide, improvements have occurred in the understanding and technology of HLA
      matching, there have been many changes in clinical practice and supportive care,
      and the more common graft source has shifted from bone marrow (BM) to peripheral
      blood stem cells (PBSCs). The percentage of older patients who are receiving
      unrelated donor transplants is increasing; currently over 1 in 10 adult
      transplant recipients is over the age of 60 years. Chronic myelogenous leukemia
      (CML) was previously the most common diagnosis for unrelated donor
      transplantation, but it now comprises less than 10% of transplants for adult
      recipients. Transplants for acute myelogenous leukemia (AML), acute lymphoblastic
      leukemia (ALL), non-Hodgkin lymphoma (NHL), and myelodysplastic syndromes (MDS)
      all outnumber CML. Treatment-related mortality (TRM) has declined significantly
      over the years, particularly in association with myeloablative transplant
      preparative regimens. Correspondingly, survival within each disease category has
      improved. Particularly gratifying are the results in severe aplastic anemia (AA)
      where 2-year survival has doubled in just 10 years.

PMID- 18721776
TI  - Twenty years of unrelated donor bone marrow transplantation for pediatric acute
      leukemia facilitated by the National Marrow Donor Program.
AB  - The National Marrow Donor Program (NMDP) has facilitated unrelated donor
      hematopoietic cell transplants for more than 20 years. In this time period, there
      have been many changes in clinical practice, including improvements in HLA typing
      and supportive care, and changes in the source of stem cells. Availability of
      banked unrelated donor cord blood (incorporated into the NMDP registry in 2000)
      as a source of stem cells has become an important option for children with
      leukemia, offering the advantages of immediate availability for children with
      high-risk disease, the need for a lesser degree of HLA match, and expanding
      access for those with infrequent HLA haplotypes. Overall survival (OS) in
      children with acute leukemia transplanted with unrelated donor bone marrow (BM)
      is markedly better in more recent years, largely attributable to less treatment
      related mortality (TRM). Within this cohort, 2-year survival was markedly better
      for patients with acute lymphoblastic leukemia (ALL) in first complete response
      (CR1) (74%) versus second complete response (CR2) (62%) or more advanced disease
      (33%). Similar findings are observed with patients with AML, suggesting earlier
      referral to bone marrow transplant (BMT) is optimal for survival. Notably, this
      improvement over time was not observed in unmodified peripheral blood stem cell
      (PBSC) recipients, suggesting unmodified PBSC may not be the optimal stem cell
      source for children.

PMID- 18721777
TI  - Donation activities and product integrity in unrelated donor allogeneic
      hematopoietic transplantation: experience of the National Marrow Donor Program.
AB  - Despite many clinical advances in allogeneic hematopoietic cell transplantation
      (HCT), the one factor that is consistently required to apply HCT to a wide
      variety of diseases is the successful donation and the safe transport and
      administration of viable donor cells to the HCT recipient. Since 1987, the
      National Marrow Donor Program (NMDP) has maintained a registry of volunteer HCT
      donors for those patients who lack a suitable related donor, facilitated the
      donor search, and managed the collection and transportation of donor cells to
      transplant centers for use in increasingly complex therapies. The NMDP has
      collected data on marrow and peripheral blood stem cell (PBSC) donations as well
      as additional donations of lymphocytes, whole blood, or platelets. These
      additional donations are provided for a variety of reasons, including treating
      post-transplant complications such as graft failure or relapsed disease,
      supporting immune reconstitution or providing transfusion support. For donor
      safety, rates of placement of central venous catheters for collecting PBSC are
      monitored. Data have also been collected on rare events that may affect the
      integrity of the HCT product (e.g., graft clotting or leaks from the transport
      bag). Quality assurance and review of these donation processes is an essential
      component of the transplantation approach. Data from the broad NMDP experience
      further illuminate factors surrounding the donation process and product
      integrity.

PMID- 18721778
TI  - Recovery and safety profiles of marrow and PBSC donors: experience of the
      National Marrow Donor Program.
AB  - The National Marrow Donor Program (NMDP) has been facilitating hematopoietic cell
      transplants since 1987. Volunteer donors listed on the NMDP Registry may be asked
      to donate either bone marrow (BM) or peripheral blood stem cells (PBSC); however,
      since 2003, the majority of donors (72% in 2007) have been asked to donate PBSC.
      From the donor's perspective these stem cell sources carry different recovery and
      safety profiles. The majority of BM and PBSC donors experienced symptoms during
      the course of their donation experience. Pain is the number 1 symptom for both
      groups of donors. BM donors most often reported pain at the collection site (82%
      back or hip pain) and anesthesia-related pain sites (33% throat pain; 17% post
      anesthesia headache), whereas PBSC donors most often reported bone pain (97%) at
      various sites during filgrastim administration. Fatigue was the second most
      reported symptom by both BM and PBSC donors (59% and 70%, respectively). PBSC
      donors reported a median time to recovery of 1 week compared to a median time to
      recovery of 3 weeks for BM donors. Both BM and PBSC donors experienced transient
      changes in their WBC, platelet, and hemoglobin counts during the donation
      process, with most counts returning to baseline values by 1 month post-donation
      and beyond. Serious adverse events are uncommon, but these events occurred more
      often in BM donors than PBSC donors (1.34% in BM donors, 0.6% in PBSC donors) and
      a few BM donors may have long-term complications. NMDP donors are currently
      participating in a randomized clinical trial that will formally compare the
      clinical and quality-of-life outcomes of BM and PBSC donors and their graft
      recipients.

PMID- 18721779
TI  - Advances in the selection of HLA-compatible donors: refinements in HLA typing and
      matching over the first 20 years of the National Marrow Donor Program Registry.

PMID- 18721780
TI  - National marrow donor program HLA matching guidelines for unrelated adult donor
      hematopoietic cell transplants.

PMID- 18721781
TI  - The contribution of distant hybridization with decaploid Agropyron elongatum to
      wheat improvement in China.
AB  - Wheat is a staple food crop in the world as well as in China. Because of the
      progress of wheat breeding and other agricultural scitechnologies, the wheat
      grain yield per unit area has increased more than five folds from 1952 to 2006 in
      China. The first part of this article briefly reviews the history of wheat
      breeding in China. Second, the establishment of "Triticum aestivum-Agropyron"
      distant hybridization system and its contribution to wheat production and
      breeding in China are summarized. Finally, the future challenges of wheat
      breeding are discussed, which include how to increase the utilization
      efficiencies of water, soil nutrient and light energy through breeding. As an
      example, our research progress on how to increase light use efficiency in wheat
      through breeding is introduced and discussed.

PMID- 18721783
TI  - A nuclear localized protein ZCCHC9 is expressed in cerebral cortex and suppresses
      the MAPK signal pathway.
AB  - The CCHC-type zinc finger motif has numerous biological activities (such as DNA
      binding and RNA binding) and can also mediate protein-protein interaction. This
      article gives a primary report about the human ZCCHC9 gene. Protein ZCCHC9
      contains four CCHC motifs and is highly conserved in humans, mice, and rats. The
      whole cDNA sequence of the ZCCHC9 gene has been amplified by PCR and a number of
      plasmids have been constructed for further study. The results show that ZCCHC9 is
      localized in the nucleus, and especially concentrated in the nucleolus. It is
      highly expressed in the brain and testicles of the mouse. This has been confirmed
      by real-time reverse transcription polymerase chain reaction (RT-PCR). In situ
      hybridization of the mouse brain indicates that ZCCHC9 is mainly expressed in the
      cerebral cortex. Reporter gene assay shows that ZCCHC9 suppresses the
      transcription activities of NF-kappa B and SRE, and may play roles in the Mitogen
      Activated Protein Kinase (MAPK) signaling transduction pathway.

PMID- 18721782
TI  - Transgenic analyses of TGIF family proteins in Drosophila imply their role in
      cell growth.
AB  - TG-interacting factors (TGIFs) belong to a family of TALE-homeodomain proteins
      including TGIF, TGIF2, and TGIF2LX/Y (TGIF2 like on X or Y chromosome) in human.
      They potentially play important functions in various tissues during development.
      Mutations in TGIF are frequently associated with malformation of forebrain and
      facial structures; TGIF2 proteins are over-expressed in many ovarian cancer cell
      lines; and TGIF2LX/Y are specifically expressed in adult testis. The molecular
      functions of these proteins have been investigated mostly in cultured cells. TGIF
      and TGIF2 have been found as transcriptional repressors that modulate TGF-beta
      signaling. However, these findings are far from sufficient to explain their
      mutant phenotypes or expression patterns, and the functions of TGIF2LX/Y have
      never been reported. Here we use Drosophila as a model system to explore the
      functions of TGIF family proteins in vivo. We observed in fly tissues such as fat
      body, epithelia, and neuronal cells, that expressing human TGIF2 or human TGIF2LX
      generally inhibited cell growth in size and number. Co-expressing Drosophila Myc,
      Cyclin E, or human c-MycS partially rescued the growth inhibition induced by
      human TGIFs, whereas activated insulin pathway signaling did not. Taken together,
      we provide in vivo evidence for the potential functions of human TGIF2 and
      TGIF2LX in growth control. Additionally, we confirmed that Drosophila TGIFs are
      transcriptional activators by assaying their activities in spermatogenesis.

PMID- 18721784
TI  - Comparison of QTLs for rice seedling morphology under different water supply
      conditions.
AB  - The variation of seedling characteristics under different water supply conditions
      is strongly associated with drought resistance in rice (Oryza sativa L.) and a
      better elucidation of its genetics is helpful for improving rice drought
      resistance. Ninetysix doubled-haploid (DH) rice lines of an indica and japonica
      cross were grown in both flooding and upland conditions and QTLs for
      morphological traits at seedling stage were examined using 208 restriction
      fragment length polymorphism (RFLP) and 76 microsatellite (SSR) markers. A total
      of 32 putative QTLs were associated with the four seedling traits: average of
      three adventitious root lengths (ARL), shoot height (SH), shoot biomass (SW), and
      root to shoot dry weight ratio (RSR). Five QTLs detected were the same under
      control and upland conditions. The ratio between the mean value of the seedling
      trait under upland and flooding conditions was used for assessing drought
      tolerance. A total of six QTLs for drought tolerance were detected. Comparative
      analysis was performed for the QTLs detected in this case and those reported from
      two other populations with the same upland rice variety Azucena as parent.
      Several identical QTLs for seedling elongation across the three populations with
      the positive alleles from the upland rice Azucena were detected, which suggests
      that the alleles of Azucena might be involved in water stress-accelerated
      elongation of rice under different genetic backgrounds. Five cell wall-related
      candidate genes for OsEXP1, OsEXP2, OsEXP4, EXT, and EGase were mapped on the
      intervals carrying the QTLs for seedling traits.

PMID- 18721785
TI  - Comparative analysis of mitochondrial fragments transferred to the nucleus in
      vertebrate.
AB  - Mitochondrial DNA sequences transferred to the nucleus give rise to the socalled
      nuclear mitochondrial DNA (numt). In the GenBank database, 244 numts have been
      found in six orders of birds (Anseriformes, Columbiformes, Falconiformes,
      Charadriiformes, Galliformes and Passeriformes). Sequences alignment (NCBI
      BLASTN) was carried out with mitochondrial and corresponding nuclear genome
      sequences in nine vertebrate species. The sequences with high homology were
      considered as numts. The number of numts ranged from 15 in chicken to 159 in
      chimpanzee. The sequences of numts in macaque, chimpanzee, and human spanned 100%
      of the entire mammalian mitochondrial genome. The reconstructed frequency of the
      mitochondrial gene transferred to the nucleus demonstrated that the rRNA genes
      had high frequencies than other mitochondrial genes. Using the RepeatMasker
      program, the transposable elements were detected in the flanking regions of each
      numt. The results showed that less than 5% of the flanking sequences were made up
      of repetitive elements in chicken. The GC content of 5'- and 3'-flanking regions
      of numts in nine species was less than 44%. The analysis of the flanking
      sequences provided a valuable understanding for future study on mechanism of
      mitochondrial gene transfer to the nucleus and the site of numt integration.

PMID- 18721786
TI  - A preliminary investigation on genetic diversity of Sousa chinensis in the Pearl
      River Estuary and Xiamen of Chinese waters.
AB  - In this study, the mitochondrial DNA (mtDNA) control region and the mitochondrial
      cytochrome b gene of stranded Indo-Pacific humpback dolphin (Sousa chinensis)
      samples from the Pearl River Estuary and Xiamen waters were sequenced and
      analyzed. The result of mtDNA control region revealed 34 variable sites and four
      unique haplotypes (named as A, B, C and D) identified among the total samples
      from these two water areas, and the most common haplotype (A) was shared by 75%
      of the dolphins sampled from the two water areas. The haplotypic diversity (h)
      was 0.455 and the nucleotide diversity (pi) was 0.0088. The phylogenetic analysis
      showed that the haplotype A, C, and D were closely related, but the haplotype B
      (unique for XM01 from Xiamen) was far from the other three. By scanning
      cytochrome b fragments, two haplotypes (A and B) were identified in these two
      water areas, and the most common haplotype (A) was shared by 91.67% individuals,
      while XM01 from Xiamen as the only exception. The data suggest that there is a
      possibility of gene exchange between the two populations in the Pearl River
      Estuary and Xiamen waters, and there possibly exists a unique maternal lineage in
      Xiamen waters.

PMID- 18721787
TI  - Prospect of the QTL-qSB-9Tq utilized in molecular breeding program of japonica
      rice against sheath blight.
AB  - The major QTL-qSB-9(Tq) conferring partial resistance to rice (Oryza sativa L.)
      sheath blight (Rhizoctonia solani Kuhn) has been verified on chromosome 9 of the
      indica rice cultivar, Teqing. In this study, the prospect of this QTL utilized in
      molecular breeding program of japonica rice for sheath blight resistance was
      investigated. Most of the japonica rice cultivars showed lower level of sheath
      blight resistance than the indica rice cultivars. At the corresponding site of
      qSB-9(Tq), nine typical japonica rice cultivars from different ecological regions
      or countries proved to possess the susceptible allele(s). Introgression of qSB
      9(Tq) into these cultivars enhanced their resistance level by decreasing sheath
      blight score of 1.0 (0.5-1.3), which indicated that qSB-9(Tq) had a large
      potential in strengthening the resistance of japonica rice to sheath blight. The
      use of the three molecular markers, which were polymorphic between Teqing and
      many japonica rice cultivars, promotes the application of qSB-9(Tq) in a concrete
      molecular breeding program.

PMID- 18721788
TI  - Characterization of Ser73 in Arabidopsis thaliana Glutathione S-transferase zeta
      class.
AB  - Glutathione S-transferases (GSTs) are ubiquitous detoxifying superfamily enzymes.
      The zeta class GST from Arabidopsis thaliana (AtGSTZ) can efficiently degrade
      dichloroacetic acid (DCA), which is a common carcinogenic contaminant in drinking
      water. Ser73 in AtGSTZ is a conserved residue at Glutathione binding site (G
      site). Compared with the equivalent residues in other GSTs, the catalytic and
      structural properties of Ser73 were poorly investigated. In this article, site
      saturation mutagenesis was performed to characterize the detailed role of Ser73.
      The DCA dechlorinating (DCA-DC) activity showed that most of the mutants had less
      than 3% of the wild-type activity, except S73T and S73A showing 43.48% and 21.62%
      of the wild-type activity, respectively, indicating that position 73 in AtGSTZ
      showed low mutational substitutability. Kinetic experiments revealed that mutants
      S73T, S73A, and S73G showed low binding affinity and catalytic efficiency toward
      DCA, 1.8-, 3.1-, and 10.7-fold increases in K(m)(DCA) values and 4.0-, 9.6-, and
      34.1-fold decreases in K(cat-)(DCA)/K(m)(DCA) values, respectively, compared to
      the wild type. Thermostability and refolding experiments showed that the wild
      type maintained more thermostability and recovered activity. These results
      demonstrated the important role of Ser73 in catalytic activity and structural
      stability of the enzyme. Such properties of Ser73 could be particularly crucial
      to the molecular evolution of AtGSTZ and might, therefore, help explain why Ser73
      is conserved in all GSTs. This conclusion might provide insights into the
      directed evolution of the DCA-DC activity of AtGSTZ.

PMID- 18721789
TI  - Carriage of Leptospira interrogans among domestic rats from an urban setting
      highly endemic for leptospirosis in Brazil.
AB  - A survey was conducted to identify reservoirs for urban leptospirosis in the city
      of Salvador, Brazil. Sampling protocols were performed in the vicinity of
      households of severe leptospirosis cases identified during active hospital-based
      surveillance. Among a total of 142 captured Rattus norvegicus (Norwegian brown
      rat), 80.3% had a positive culture isolate from urine or kidney specimens and
      68.1% had a positive serum sample by microscopic agglutination test (MAT) titre
      of > or = 1:100. Monoclonal antibody-based typing of isolates identified that the
      agent carried by rats was Leptospira interrogans serovar Copenhageni, which was
      the same serovar isolated from patients during hospital-based surveillance.
      Leptospira spp. were not isolated from 8 captured Didelphis marsupialis
      (Opossum), while 5/7 had a positive MAT titre against a saprophytic serogroup. R.
      rattus were not captured during the survey. The study findings indicate that the
      brown rat is a major rodent reservoir for leptospirosis in this urban setting.
      Furthermore, the high carriage rates of L. interrogans serovar Copenhageni in
      captured rats suggest that there is a significant degree of environmental
      contamination with this agent in the household environment of high risk areas,
      which in turn is a cause of transmission during urban epidemics.

PMID- 18721790
TI  - Subunit analysis of bovine heart complex I by reversed-phase high-performance
      liquid chromatography, electrospray ionization-tandem mass spectrometry, and
      matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry.
AB  - An effective method was developed for isolation and analysis of bovine heart
      complex I subunits. The method uses C18 reversed-phase high-performance liquid
      chromatography (HPLC) and a water/acetonitrile gradient containing 0.1%
      trifluoroacetic acid. Employing this system, 36 of the 45 complex I subunits
      elute in 28 distinct chromatographic peaks. The 9 subunits that do not elute are
      B14.7, MLRQ, and the 7 mitochondrial-encoded subunits. The method, with
      ultraviolet (UV) detection, is suitable for either analytical (<50 microg
      protein) or preparative (>250 microg protein) applications. Subunits eluting in
      each chromatographic peak were initially determined by matrix-assisted laser
      desorption/ionization-time-of-flight/mass spectrometry (MALDI-TOF/MS) with
      subsequent positive identification by reversed-phase HPLC-electrospray ionization
      (ESI)/tandem mass spectrometry (MS/MS) analysis of tryptic digests. In the latter
      case, subunits were identified with a 99% probability using Mascot for database
      searching and Scaffold for assessment of protein identification probabilities.
      The reversed-phase HPLC subunit analysis method represents a major improvement
      over previous separation methods with respect to resolution, simplicity, and ease
      of application.

PMID- 18721791
TI  - Compound C inhibits clonal expansion of preadipocytes by increasing p21 level
      irrespectively of AMPK inhibition.
AB  - AMP-activated protein kinase (AMPK) activation inhibits adipocyte
      differentiation. This study investigated the effect of compound C (CC), a widely
      used AMPK inhibitor, on differentiation of 3T3-L1 preadipocytes. CC treatment
      blocked hormone-induced preadipocyte differentiation due to inhibition of mitotic
      clonal expansion, which was accompanied by the failure of degradation of p21, a
      cyclin-dependent kinase inhibitor. CC increased the level of p21 protein, but not
      its mRNA, in preadipocytes incubated in a hormone-free medium. Cycloheximide
      decreased the basal p21 level, which was inhibited by CC treatment, supporting
      the stabilization of p21 by CC. Treatment of AICAR or metformin, AMPK activators,
      failed to induce p21 or inhibit the ability of CC to increase p21 level. In
      conclusion, CC inhibits proliferation of preadipocytes as a consequence of an
      increase in p21 content, which might result from p21 stabilization, and the
      increase in p21 level by CC might not be associated with AMPK inhibition.

PMID- 18721792
TI  - Solution-state characteristics of the ultraviolet A-induced visible fluorescence
      from proteins.
AB  - In response to illumination by ultraviolet-A (UV-A) light, proteins in solid form
      are now known to display a visible blue fluorescence, ostensibly on account of
      excitation transitions of loosely-held electrons within peptide bond orbitals
      engaged in hydrogen bonding. Because the CO and NH atom groups in peptide bonds
      are generally engaged in extensive hydrogen bonding in globular proteins even in
      aqueous solution, one could argue that proteins in solution must also display
      this novel blue fluorescence. Here, using high concentrations to enhance
      detectability, two globular proteins, gamma-crystallin, and lysozyme, are shown
      to fluoresce visibly, exhibiting: (a) two excitation maxima, at approximately 315
      nm and approximately 385 nm, (b) maximal emission at 425 nm in 100 mg/ml lysozyme
      and 465 nm in 100 mg/ml gamma-crystallin, (c) a time-resolved emission decay that
      is best fitted by a sum of three exponentials with lifetimes of 3.14, 0.46, and
      9.08 ns, respectively, and comparable relative amplitudes of around 30-40 percent
      each, and (d) a weak CD spectrum displaying a positive band at approximately 385
      nm and a negative band at approximately 465 nm. While the wavelength of maximal
      emission ((em)lambda(max)) in lysozyme is the same for all protein
      concentrations, the (em)lambda(max) of gamma-crystallin varies with protein
      concentration, suggesting a certain degree of conformation dependence.

PMID- 18721793
TI  - Membrane phospholipids, lipoxidative damage and molecular integrity: a causal
      role in aging and longevity.
AB  - Nonenzymatic molecular modifications induced by reactive carbonyl species (RCS)
      generated by peroxidation of membrane phospholipids acyl chains play a causal
      role in the aging process. Most of the biological effects of RCS, mainly
      alpha,beta-unsaturated aldehydes, di-aldehydes, and keto-aldehydes, are due to
      their capacity to react with cellular constituents, forming advanced lipoxidation
      end-products (ALEs). Compared to reactive oxygen and nitrogen species, lipid
      derived RCS are stable and can diffuse within or even escape from the cell and
      attack targets far from the site of formation. Therefore, these soluble reactive
      intermediates, precursors of ALEs, are not only cytotoxic per se, but they also
      behave as mediators and propagators of oxidative stress and cellular and tissue
      damage. The consequent loss-of-function and structural integrity of modified
      biomolecules can have a wide range of downstream functional consequences and may
      be the cause of subsequent cellular dysfunctions and tissue damage. The causal
      role of ALEs in aging and longevity is inferred from the findings that follow: a)
      its accumulation with aging in several tissues and species; b) physiological
      interventions (dietary restriction) that increase longevity, decrease ALEs
      content; c) the longer the longevity of a species, the lower is the lipoxidation
      derived molecular damage; and finally d) exacerbated levels of ALEs are
      associated with pathological states.

PMID- 18721794
TI  - Membrane insertion of the three main membranotropic sequences from SARS-CoV S2
      glycoprotein.
AB  - In order to complete the fusion process of SARS-CoV virus, several regions of the
      S2 virus envelope glycoprotein are necessary. Recent studies have identified
      three membrane-active regions in the S2 domain of SARS-CoV glycoprotein, one
      situated downstream of the minimum furin cleavage, which is considered the fusion
      peptide (SARSFP), an internal fusion peptide located immediately upstream of the
      HR1 region (SARSIFP) and the pre-transmembrane domain (SARSPTM). We have explored
      the capacity of these selected membrane-interacting regions of the S2 SARS-CoV
      fusion protein, alone or in equimolar mixtures, to insert into the membrane as
      well as to perturb the dipole potential of the bilayer. We show that the three
      peptides interact with lipid membranes depending on lipid composition and
      experiments using equimolar mixtures of these peptides show that different
      segments of the protein may act in a synergistic way suggesting that several
      membrane-active regions could participate in the fusion process of the SARS-CoV.

PMID- 18721795
TI  - Phospholipid-induced structural changes to an erythroid beta spectrin ankyrin
      dependent lipid-binding site.
AB  - The region of beta-spectrin that is responsible for interactions with ankyrin was
      shown to comprise an ankyrin-sensitive lipid-binding site. Structural studies
      indicate that it exhibits a mixed 3(10)/alpha helical conformation and is highly
      amphipathic. These features together with the distinctively conserved sequence of
      the lipid-binding site motivated us to explore the mechanism of its interactions
      with biological membranes. A series of singly and doubly spin-labeled erythroid
      beta-spectrin-derived peptides was constructed, and the spin-label mobility and
      spin-spin distances were analyzed via electron paramagnetic resonance
      spectroscopy and two different calculation methods. The results indicate that in
      beta-spectrin, the lipid-binding domain, which is part of the 14(th) segment, has
      the topology of typical triple-helical spectrin repeat. However, it undergoes
      significant changes when interacting with phospholipids or detergents. A
      mechanism for these interactions is proposed in this paper.

PMID- 18721796
TI  - Metformin enhances the differentiation and mineralization of osteoblastic MC3T3
      E1 cells via AMP kinase activation as well as eNOS and BMP-2 expression.
AB  - It is unclear whether metformin, one of the anti-hyperglycemic agents commonly
      used for type 2 diabetes, could affect bone formation through activation of AMP
      activated protein kinase (AMPK). In order to clarify this issue, we investigated
      the effects of metformin on the differentiation and mineralization of
      osteoblastic MC3T3-E1 cells as well as intracellular signal transduction.
      Metformin (50 microM) significantly increased collagen-I and osteocalcin mRNA
      expression, stimulated alkaline phosphatase activity, and enhanced cell
      mineralization. Moreover, metformin significantly activated AMPK in dose- and
      time-dependent manners, and induced endothelial nitric oxide synthase (eNOS) and
      bone morphogenetic protein-2 (BMP-2) expressions. Supplementation of Ara-A
      (0.1mM), a specific AMPK inhibitor, significantly reversed the metformin-induced
      eNOS and BMP-2 expressions. Our findings suggest that metformin can induce the
      differentiation and mineralization of osteoblasts via activation of the AMPK
      signaling pathway, and that this drug might be beneficial for not only diabetes
      but also osteoporosis by promoting bone formation.

PMID- 18721797
TI  - Temperature sensitivity of phospho-Ser(473)-PKB/AKT.
AB  - The phospho-PKB/Akt status is often used as surrogate marker to measure
      activation of the PI3K/Akt/mTOR signal transduction pathway. Though,
      inconsistencies of the p-Ser(473)-PKB/Akt status have raised doubts in the
      validity of p-Ser(473)-PKB/Akt phosphorylation as endpoint. Here, we determined
      that p-Ser(473)-PKB/Akt but not p-Thr(308)-PKB/Akt phosphorylation is highly
      temperature sensitive. p-Ser(473)-PKB/Akt phosphorylation was rapidly reduced to
      levels below 50% on exposure to 20-25 degrees C in murine and human cell lines
      including cells expressing constitutively active PI3K or lacking PTEN. Down
      regulation of p-Ser(473)-PKB/Akt was reversible and re-exposure to physiological
      temperature resulted in increased p-Ser(473)-PKB/Akt phosphorylation levels.
      Phosphatase activity at low temperature was sustained at 75% baseline level and
      phosphatase inhibition prevented p-Ser(473)-PKB/Akt dephosphorylation induced by
      the low temperature shift. Interestingly temperature-dependent deregulation of
      the p-Ser(473)-PKB/Akt status was also observed in response to irradiation. Thus
      our data demonstrate that minimal additional stress factors deregulate the
      PI3K/Akt-survival pathway and the p-Ser(473)-PKB/Akt status as experimental
      endpoint.

PMID- 18721798
TI  - Intermittent L-DOPA treatment differentially alters synaptotagmin 4 and 7 gene
      expression in the striatum of hemiparkinsonian rats.
AB  - Long-term use of L-DOPA in Parkinson's disease (PD) is frequently associated with
      side effects that are reflected in changed neurotransmitter/neuropeptide
      secretion in basal ganglia. These side effects could be connected with
      synaptotagmins (syts) because syts are involved in regulation of membrane
      trafficking. We have previously reported that acute L-DOPA treatment upregulated
      the expression of Syt 4 and Syt 7 mRNAs in hypersensitive striatum of 6-OHDA rat
      model for PD. Here we investigate whether intermittent L-DOPA treatment that
      produces behavior sensitization affects the Syt 1, Syt 2, Syt 4, Syt 7 and Syt 10
      mRNAs in striatum of 6-OHDA rats killed 4 and 12 h after the last L-DOPA
      injection. We verified behavioral sensitization by increased intensity of
      contralateral turning. 6-OHDA lesion caused Syt 2 mRNA downregulation and Syt 10
      mRNA upregulation in striatum, but failed to alter Syt 4, Syt 7 and Syt 1 mRNAs.
      Acute l-DOPA induced an increase of Syt 4 and Syt 7 mRNAs in the denervated
      striatum leaving the levels of Syt 1, Syt 2 and Syt 10 mRNAs unaffected.
      Intermittent L-DOPA treatment did not alter Syt 1, Syt 2 and Syt 10 mRNA striatal
      levels, suggesting that 6-OHDA-induced Syt 2 and Syt 10 mRNA changes reflect a
      persistent striatal abnormality caused by dopamine depletion. On contrary,
      intermittent L-DOPA treatment downregulated Syt 4 mRNA and prolonged the
      elevation of Syt 7 mRNA in the denervated striatum. We conclude that Syt 4 and
      Syt 7 might be specifically involved in striatal plasticity caused by repeated L
      DOPA administration that accompanies sensitization.

PMID- 18721799
TI  - Structural changes in dipalmitoylphosphatidylcholine bilayer promoted by Ca2+
      ions: a small-angle neutron scattering study.
AB  - Small-angle neutron scattering (SANS) curves of unilamellar
      dipalmitoylphosphatidylcholine (DPPC) vesicles in 1-60mM CaCl2 were analyzed
      using a strip-function model of the phospholipid bilayer. The fraction of Ca2+
      ions bound in the DPPC polar head group region was determined using Langmuir
      adsorption isotherm. In the gel phase, at 20 degrees C, the lipid bilayer
      thickness, dL, goes through a maximum as a function of CaCl2 concentration
      (dL=54.4A at approximately 2.5mM of CaCl2). Simultaneously, both the area per
      DPPC molecule AL, and the number of water molecules nW located in the polar head
      group region decrease (DeltaAL=AL(DPPC))-AL(DPPC+Ca)=2.3A2 and Deltan=n(W(DPPC))
      n(W(DPPC+Ca))=0.8mol/mol at approximately 2.5mM of CaCl2). In the fluid phase, at
      60 degrees C, the structural parameters d(L), A(L), and n(W) show evident changes
      with increasing Ca2+ up to a concentration C(Ca)(2+) < or = 10mM. DPPC bilayers
      affected by the calcium binding are compared to unilamellar vesicles prepared by
      extrusion. The structural parameters of DPPC vesicles prepared in 60mM CaCl2 (at
      20 and 60 degrees C) are nearly the same as those for unilamellar vesicles
      without Ca2+.

PMID- 18721800
TI  - The effects of high fat on central appetite genes in Wistar rats: a microarray
      analysis.
AB  - BACKGROUND: To evaluate the effects of high fat on central appetite regulatory
      genes in Wistar rats by microarray. METHODS: Sixteen male Wistar rats were
      randomly assigned to control (15% energy from fat) and high-fat (60% energy from
      fat) diets for 12 weeks. Body weight and food intake were recorded. Plasma
      leptin, ghrelin and insulin were measured by radioimmunoassay method. The
      expression of 111 appetite regulatory genes in the hypothalamus was evaluated by
      microarray and six genes, including leptin receptor, insulin receptor, orexin,
      NPY, AgRP, MC-4R, were further evaluated by real-time RT-PCR. RESULTS: Body
      weight increased significantly in HF group compared with control group, whereas
      energy intake was similar in the two groups. HF had a time dependent effect on
      plasma leptin, but insulin and ghrelin level remained stable throughout the
      study. A positive relation was also found between body weight and plasma leptin
      (r=0.88, P<0.01). The expression of 27 appetite genes in the hypothalamus was
      significantly affected by HF diet. However, only the expression of leptin
      receptor was confirmed lower in HF group than that in control by real-time PCR,
      which suggested that lower expression of leptin receptor might be another reason
      for leptin resistance. CONCLUSIONS: HF diet fed rats demonstrated leptin
      resistance, which could be targeted for obesity treatment.

PMID- 18721801
TI  - Myogenin regulates a distinct genetic program in adult muscle stem cells.
AB  - In contrast to the detailed understanding we have for the regulation of skeletal
      muscle gene expression in embryos, similar insights into postnatal muscle growth
      and regeneration are largely inferential or do not directly address gene
      regulatory mechanisms. Muscle stem cells (satellite cells) are chiefly
      responsible for providing new muscle during postnatal and adult life. The purpose
      of this study was to determine the role that the myogenic basic helix-loop-helix
      regulatory factor myogenin has in postnatal muscle growth and adult muscle stem
      cell gene expression. We found that myogenin is absolutely required for skeletal
      muscle development and survival until birth, but it is dispensable for postnatal
      life. However, Myog deletion after birth led to reduced body size implying a role
      for myogenin in regulating body homeostasis. Despite a lack of skeletal muscle
      defects in Myog-deleted mice during postnatal life and the efficient
      differentiation of cultured Myog-deleted adult muscle stem cells, the loss of
      myogenin profoundly altered the pattern of gene expression in cultured muscle
      stem cells and adult skeletal muscle. Remarkably, these changes in gene
      expression were distinct from those found in Myog-null embryonic skeletal muscle,
      indicating that myogenin has separate functions during postnatal life.

PMID- 18721802
TI  - Hairy2-Id3 interactions play an essential role in Xenopus neural crest progenitor
      specification.
AB  - Loss of function studies have shown that the Xenopus helix-loop-helix
      transcription factor Hairy2 is essential for neural crest formation and maintains
      cells in a mitotic undifferentiated state. However, its position in the genetic
      cascade regulating neural crest formation and its relationship with other neural
      crest regulators remain largely unknown. Here we find that Hairy2 is regulated by
      BMP, FGF and Wnt and that it is only required downstream of BMP and FGF for
      neural crest formation. We show that Hairy2 overexpression represses neural crest
      and upregulates neural border genes at early stages while it expands a subset of
      them in later embryos. We show that Hairy2 downregulates Id3, another essential
      HLH neural crest regulator, through attenuation of BMP signaling. Knockdown and
      rescue experiments indicate that Id3 protein, which physically interacts with
      Hairy2, negatively regulates Hairy2 activity. However, Id3 is required to allow
      Hairy2 to promote neural crest formation. Together, our results provide evidence
      that Hairy2 acts downstream of FGF and BMP signals at the neural border to
      maintain cells in an undifferentiated state, and that Hairy2-Id3 interactions
      play an essential role in neural crest progenitor specification.

PMID- 18721803
TI  - A transcriptional network coordinately determines transmitter and peptidergic
      fate in the dorsal spinal cord.
AB  - Dorsal horn neurons express many different neuropeptides that modulate sensory
      perception like the sensation of pain. Inhibitory neurons of the dorsal horn
      derive from postmitotic neurons that express Pax2, Lbx1 and Lhx1/5, and diversify
      during maturation. In particular, fractions of maturing inhibitory neurons
      express various neuropeptides. We demonstrate here that a coordinate molecular
      mechanism determines inhibitory and peptidergic fate in the developing dorsal
      horn. A bHLH factor complex that contains Ptf1a acts as upstream regulator and
      initiates the expression of several downstream transcription factors in the
      future inhibitory neurons, of which Pax2 is known to determine the
      neurotransmitter phenotype. We demonstrate here that dynorphin, galanin, NPY,
      nociceptin and enkephalin expression depends on Ptf1a, indicating that these
      neuropeptides are expressed in inhibitory neurons. Furthermore, we show that
      Neurod1/2/6 and Lhx1/5, which act downstream of Ptf1a, control distinct aspects
      of peptidergic differentiation. In particular, the Neurod1/2/6 factors are
      essential for dynorphin and galanin expression, whereas the Lhx1/5 factors are
      essential for NPY expression. We conclude that a transcriptional network operates
      in maturing dorsal horn neurons that coordinately determines transmitter and
      peptidergic fate.

PMID- 18721804
TI  - kappa-Opioid receptor stimulation inhibits augmentation of Ca(2+) transient and
      hypertrophy induced by isoprenaline in neonatal rat ventricular myocytes - Role
      of CaMKIIdelta(B).
AB  - We aimed to further define the pathway mediating the inhibitory effects of kappa
      opioid receptor stimulation on Ca(2+) transients and hypertrophic responses to
      beta(1)-adrenoceptor stimulation. We determined the effects of trans-(+/-)-3,4
      dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamid
      methanesulfonate salt (U50,488H), a selective kappa-opioid receptor agonist, on
      the enhancement of spontaneous Ca(2+) transients and the induction of hypertrophy
      by isoprenaline, a beta-adrenoceptor agonist, in cultured neonatal ventricular
      myocytes. The results were compared with those found with KN93, a selective
      Ca(2+)/calmodulin-dependent kinase (CaMKII) inhibitor, propranolol, a beta
      adrenoceptor antagonist, and verapamil, a L-type Ca(2+) channel antagonist.
      Hypertrophy of cardiomyocytes was characterized by increases in (i) total protein
      content; (ii) cell size; and (iii) [(3)H]leucine incorporation. 10 micromol/l
      isoprenaline increased all three parameters. We also determined the expression of
      nuclear CaMKIIdelta in response to U50,488H in the presence or absence of
      isoprenaline. To determine whether the effects of U50,488H were receptor
      mediated, its effects were also measured following blockade of the kappa-opioid
      receptor with nor-binaltorphimine. kappa-Opioid receptor stimulation suppressed
      the stimulatory effect of isoprenaline on Ca(2+) transients and cardiac
      hypertrophy, as did KN93, propranalol and verapamil. U50,488H also suppressed the
      expression of nuclear CaMKIIdelta(B) in the presence, but not in the absence of
      isoprenaline. These results suggest that the inhibitory effect of kappa-opioid
      receptor stimulation on beta(1)-adrenoceptor stimulation may also involve
      CaMKIIdelta.

PMID- 18721805
TI  - Release kinetics of intact and degraded troponin I and T after irreversible cell
      damage.
AB  - PURPOSE: We characterized the release kinetics of cardiac troponin I and T in
      relation to lactate dehydrogenase (LDH) from cardiomyocytes before and after the
      transition from reversible to irreversible cell damage. METHODS: Cardiomyocytes
      were exposed to mild metabolic inhibition (1 mmol/L sodium azide) to induce a
      necrotic cell death process that is characterized by a reversible (0-12 h) and
      irreversible phase (12-30 h). At various time intervals cells and media were
      collected and analyzed for LDH activity, intact cTnI and cTnT, and their
      degradation products. RESULTS: During the first 12 h of metabolic inhibition,
      cell viability was unchanged with no release of intact cTnI and cTnT nor their
      degradation products. Between 12 and 30 h of azide treatment, cardiomyocytes
      showed progressive cell death accompanied by release of intact cTnI (29 kDa),
      intact cTnT (39 kDa), four cTnI degradation products of 26, 20, 17 and 12 kDa,
      and three cTnT degradation products of 37, 27 and 14 kDa. Possibly due to
      degradation, there is progressive loss of cTnI and cTnT protein that is obviously
      undetected by the antibodies used. CONCLUSIONS: Metabolic inhibition of
      cardiomyocytes induces a parallel release of intact cTnI and cTnT and their
      degradation products, starting only after onset of irreversible cardiomyocyte
      damage.

PMID- 18721806
TI  - ErbBs in lung cancer.
AB  - Lung cancer remains the leading cause of cancer deaths worldwide, and advanced
      stage disease is largely refractory to conventional chemotherapy. Thus, there is
      an important need for alternative treatment strategies, and the ErbB proteins
      have emerged as potentially important therapeutic drug targets in this setting,
      apparently reflecting a state of "oncogene addiction" in some lung tumors. In
      this review, we discuss the recent identification of mutations that promote
      activation of ErbB family proteins in a subset of lung cancers, and the
      development of selective inhibitors of these proteins that have demonstrated
      clinical efficacy. We also discuss the problem of drug resistance, which severely
      limits the clinical utility of such agents, and has prompted intense efforts to
      better understand molecular mechanisms underlying drug resistance as well as
      strategies to overcome or prevent such resistance.

PMID- 18721807
TI  - Sub-retinal drusenoid deposits in human retina: organization and composition.
AB  - We demonstrate histologically sub-retinal drusenoid debris in three aged human
      eyes, two of them affected by age-related maculopathy. By postmortem fundus
      examination, the lesions were drusen-like, i.e., they were pale spots apparently
      at the level of the retinal pigment epithelium (RPE). Light and electron
      microscopy revealed aggregations of membranous debris, the principal constituent
      of soft drusen, in the sub-retinal space. Immunohistochemistry and confocal
      microscopy confirmed the presence of molecules typically associated with drusen
      (positive for unesterified cholesterol, apoE, complement factor H, and
      vitronectin) without evidence for molecules associated with photoreceptors
      (lectin-binding disaccharide bridges and opsins), Muller cells (glial fibrillary
      acid protein and cellular retinal binding protein, CRALPB), or RPE (CRALPB). The
      fact that a drusenoid material, sharing some markers with conventional drusen,
      can occur on opposite faces of the RPE, suggests deranged polarity of normally
      highly vectorial processes for basolateral secretion from RPE, and that
      overproduction of secreted materials and direction of secretion are independently
      specified processes. In the future, drusenoid sub-retinal debris might be more
      frequently revealed by emerging high-resolution imaging techniques.

PMID- 18721808
TI  - Infusions of naloxone into the medial preoptic area, ventromedial nucleus of the
      hypothalamus, and amygdala block conditioned place preference induced by paced
      mating behavior.
AB  - Paced mating induces positive affect as revealed by conditioned place preference
      (CPP) in female rats. It has been suggested that endogenous opioids are involved
      in the generation of this positive affect since systemic administration of the
      opioid antagonist naloxone blocks mating-induced CPP. Several brain structures,
      including the medial preoptic area (mPOA), the ventromedial nucleus of the
      hypothalamus (VMH), the amygdala (Me), and the nucleus accumbens (Acb) have been
      implicated in the control of female sexual behavior. However, it is not known if
      these structures also participate in the positive affect produced by paced
      mating. To this end we determined the effects of intracranial administration of
      naloxone methiodide into the mPOA, VMH, Me and Acb on conditioned place
      preference induced by paced mating in female rats. Regardless of the site of
      infusion 5 micro of naloxone did not affect any of the sexual behavior parameters
      measured during copulation. When CPP was evaluated, the groups infused with
      naloxone into the mPOA, the VMH, and the Me before each conditioning session did
      not develop place preference. Only the group infused with naloxone in the Acb and
      the control groups did so. These results demonstrate that opioid receptors within
      the mPOA, VMH and Me are necessary for the rewarding aspects of paced mating. We
      suggest that the Me and VMH are important for the transmission of sensory
      information produced by copulation while the mPOA is the site where the positive
      affect is originated.

PMID- 18721809
TI  - The effects of maternal corticosterone levels on offspring behavior in fast- and
      slow-growth garter snakes (Thamnophis elegans).
AB  - During embryonic development, viviparous offspring are exposed to maternally
      circulating hormones. Maternal stress increases offspring exposure to
      corticosterone and this hormonal exposure has the potential to influence
      developmental, morphological and behavioral traits of the resulting offspring. We
      treated pregnant female garter snakes (Thamnophis elegans) with low levels of
      corticosterone after determining both natural corticosterone levels in the field
      and pre-treatment levels upon arrival in the lab. Additional measurements of
      plasma corticosterone were taken at days 1, 5, and 10 during the 10-day exposure,
      which occurred during the last third of gestation (of 4-month gestation). These
      pregnant snakes were from replicate populations of fast- and slow-growth ecotypes
      occurring in Northern California, with concomitant short and long lifespans.
      Field corticosterone levels of pregnant females of the slow-growth ecotype were
      an order of magnitude higher than fast-growth dams. In the laboratory,
      corticosterone levels increased over the 10 days of corticosterone manipulation
      for animals of both ecotypes, and reached similar plateaus for both control and
      treated dams. Despite similar plasma corticosterone levels in treated and control
      mothers, corticosterone-treated dams produced more stillborn offspring and
      exhibited higher total reproductive failure than control dams. At one month of
      age, offspring from fast-growth females had higher plasma corticosterone levels
      than offspring from slow-growth females, which is opposite the maternal pattern.
      Offspring from corticosterone-treated mothers, although unaffected in their
      slither speed, exhibited changes in escape behaviors and morphology that were
      dependent upon maternal ecotype. Offspring from corticosterone-treated fast
      growth females exhibited less anti-predator reversal behavior; offspring from
      corticosterone-treated slow-growth females exhibited less anti-predator tail
      lashing behavior.

PMID- 18721811
TI  - Three-layer ONIOM studies of the dark state of rhodopsin: the protonation state
      of Glu181.
AB  - A computational three-layer ONIOM(QM-high:QM-low:MM) hybrid scheme has been
      applied to analyze the protonation state of the Glu181 amino acid residue in
      rhodopsin, which is vital to determining the rhodopsin photoactivation mechanism.
      Due to conflicting evidence from previous studies, it has yet to be conclusively
      resolved. In this study, we fully optimize dark-state rhodopsin model structures
      differing only at the 181-residue site-protonated and unprotonated Glu181-and
      calculate several experimentally observable properties. Comparison of calculated
      structures, excitation energies, and NMR chemical shifts for the two models with
      values from the literature allows a reevaluation of previously reported
      conclusions. A key finding is that the S(1)-->S(2) energy level splitting,
      previously used as evidence for a neutral Glu181, is found to be almost identical
      for the two protonation states. We highlight a need for caution when interpreting
      experimental data. Small differences in the properties of the two model
      structures are also identified, which may be useful targets for future high
      resolution experimental approaches.

PMID- 18721810
TI  - Segregation of type I collagen homo- and heterotrimers in fibrils.
AB  - Normal type I collagen is a heterotrimer of two alpha1(I) and one alpha2(I)
      chains, but various genetic and environmental factors result in synthesis of
      homotrimers that consist of three alpha1(I) chains. The homotrimers completely
      replace the heterotrimers only in rare recessive disorders. In the general
      population, they may compose just a small fraction of type I collagen.
      Nevertheless, they may play a significant role in pathology; for example,
      synthesis of 10-15% homotrimers due to a polymorphism in the alpha1(I) gene may
      contribute to osteoporosis. Homotrimer triple helices have different stability
      and less efficient fibrillogenesis than heterotrimers. Their fibrils have
      different mechanical properties. However, very little is known about their
      molecular interactions and fibrillogenesis in mixtures with normal heterotrimers.
      Here we studied the kinetics and thermodynamics of fibril formation in such
      mixtures by combining traditional approaches with 3D confocal imaging of fibrils,
      in which homo- and heterotrimers were labeled with different fluorescent colors.
      In a mixture, following a temperature jump from 4 to 32 degrees C, we observed a
      rapid increase in turbidity most likely caused by formation of homotrimer
      aggregates. The aggregates promoted nucleation of homotrimer fibrils that served
      as seeds for mixed and heterotrimer fibrils. The separation of colors in confocal
      images indicated segregation of homo- and heterotrimers at a subfibrillar level
      throughout the process. The fibril color patterns continued to change slowly
      after the fibrillogenesis appeared to be complete, due to dissociation and
      reassociation of the pepsin-treated homo- and heterotrimers, but this remixing
      did not significantly reduce the segregation even after several days. Independent
      homo- and heterotrimer solubility measurements in mixtures confirmed that the
      subfibrillar segregation was an equilibrium property of intermolecular
      interactions and not just a kinetic phenomenon. We argue that the subfibrillar
      segregation may exacerbate effects of a small fraction of alpha1(I) homotrimers
      on formation, properties, and remodeling of collagen fibers.

PMID- 18721812
TI  - Signal discrimination by differential regulation of protein stability in quorum
      sensing.
AB  - Quorum sensing (QS) is a communication mechanism exploited by a large variety of
      bacteria to coordinate gene expression at the population level. In Gram-negative
      bacteria, QS occurs via synthesis and detection of small chemical signals, most
      of which belong to the acyl-homoserine lactone class. In such a system, binding
      of an acyl-homoserine lactone signal to its cognate transcriptional regulator (R
      protein) often induces stabilization and subsequent dimerization of the R
      protein, which results in the regulation of downstream gene expression. Existence
      of diverse QS systems within and among species of bacteria indicates that each
      bacterium needs to distinguish among a myriad of structurally similar chemical
      signals. We show, using a mathematical model, that fast degradation of an R
      protein monomer can facilitate discrimination of signals that differentially
      stabilize it. Furthermore, our results suggest an inverse correlation between the
      stability of an R-protein and the achievable limits of fidelity in signal
      discrimination. In particular, an unstable R-protein tends to be more specific to
      its cognate signal, whereas a stable R-protein tends to be more promiscuous.
      These predictions are consistent with experimental data on well-studied natural
      and engineered R-proteins and thus have implications for understanding the
      functional design of QS systems.

PMID- 18721813
TI  - Theoretical analysis of the adaptive contractile behaviour of a single
      cardiomyocyte cultured on elastic substrates with varying stiffness.
AB  - In vivo, cardiomyocytes interact with surrounding extracellular matrix while
      performing periodically a contractile behaviour, which is the main determinant of
      heart performance. As extracellular substrates with easily tunable stiffness
      properties, polyacrylamide gels (PAGs) provide valuable flexible media for
      studying in vitro the dynamical behaviour of cardiomyocytes responding to
      stiffness variations of their surrounding environment. We propose in this paper
      an original mechano-chemical model of the cardiac cell contraction that sheds
      light on the adaptive response of cardiomyocytes evidenced recently in the
      experiments of Qin et al. [2007. Dynamical stress characterization and energy
      evaluation of single cardiac myocyte actuating on flexible substrate. Biochem.
      Biophys. Res. Commun. 360, 352-356]. The model links the amplitude of the
      extracellular PAGs strain fields to the spatio-temporal variation of the
      intracellular stresses in every part of the cell during the sarcomeres
      contraction-relaxation. In a continuum mechanics framework, we derived a unified
      description of the sarcomere-length dependence of intracellular active stress and
      of its control by anisotropic calcium diffusion and autocatalytic calcium release
      from the sarcoplasmic reticulum. Taking benefit of our previous work on the
      characterization of mechanical properties of PAGs with varying stiffness, we were
      thus able to evaluate the active intracellular stress exerted by the
      cardiomyocyte on flexible PAGs with different and known Young's moduli.
      Interestingly, we were able to explain the intriguing increase of maximal
      cellular stress observed experimentally when substrate stiffness is increased. By
      providing an evaluation of the whole-field cell stresses and strains, this
      integrative approach of cardiomyocyte contraction provides a reliable basis for
      further analysis of additional cooperativity and mechanotransduction mechanisms
      involved in cell contractility regulation, notably in physiological and
      pathological situations where modifications of cardiac performance are linked to
      varied stiffness of the cardiomyocytes environment.

PMID- 18721814
TI  - A molecular model for persister in E. coli.
AB  - Like many other bacteria, Escherichia coli remain as tiny viable individuals
      named persisters after being exposed to an antibiotic. These persisters are
      believed to be phenotypic heterogeneous one rather than mutants, because their
      progenies are as susceptible to antibiotics as their ancestors. Recently, two
      persister-related genes (hipB/hipA) were confirmed to belong to a toxin-antitoxin
      (TA) module. Their control circuit was believed to be responsible for generation
      of the persister subpopulation. For the well-studied TA module, we build a simple
      genetic regulation model to explain the phenotypic heterogeneity. We find that a
      sole double-negative feedback loop is not enough to explain the phenotypic
      heterogeneity; the cooperation mechanisms in HipB and HipA are indispensable.
      Moreover, our model illustrates an important persister-related experimental
      phenomenon: the emergence of the persister depends on the growth rate in
      continuous culture.

PMID- 18721815
TI  - Tanshinone IIA, an isolated compound from Salvia miltiorrhiza Bunge, induces
      apoptosis in HeLa cells through mitotic arrest.
AB  - AIMS: Tanshinone IIA (Tan IIA) is a compound isolated from Salvia miltiorrhiza
      Bunge (Danshen). The aim of this study is to investigate the mechanisms of its
      anti-cancer effect. MAIN METHODS: To clearly delineate the cell cycle-dependent
      effects of Tan IIA, we used either synchronized cells or single living cell
      analysis to conduct our studies. Subcellular fractionation, Western blot
      analysis, immuno-fluorescence staining and FACS analysis were also employed in
      our study. KEY FINDINGS: We found that Tan IIA could arrest cancer cells in
      mitosis by disrupting the mitotic spindle and subsequently triggered cells to
      enter apoptosis through the mitochondria-dependent apoptotic pathway. Thus, Tan
      IIA could selectively kill mitotic cells over interphase cells. In comparison
      with other existing anti-cancer drugs that cause mitotic arrest by interfering
      with the microtubule structure (such as vincristine or taxol), Tan IIA destroyed
      only the mitotic spindle during the M phase but not the microtubule structure in
      interphase cells. Furthermore, Tan IIA could trigger the mitotic arrested cells
      to enter apoptosis faster than vincristine or taxol. SIGNIFICANCE: Since Tan IIA
      can selectively induce cancer cells to enter apoptosis through mitotic arrest, it
      has the potential to be developed into an anti-cancer drug.

PMID- 18721816
TI  - Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1) inhibits experimental
      autoimmune encephalomyelitis in dark Agouti (DA) rats.
AB  - Previous studies have shown that vascular endothelial growth factor (VEGF)
      expression is up-regulated in both multiple sclerosis (MS) and experimental
      autoimmune encephalomyelitis (EAE), a model for MS, and may exacerbate the
      disease. However, it remains unknown whether anti-VEGF modalities could serve as
      a potential treatment for such central nervous system (CNS) autoimmune diseases.
      We constructed a recombinant adenoviral vector carrying FLAG-tagged sFlt-1(1-3)
      (the first three extracellular domains of Flt-1, the hVEGF receptor-1).
      Intramuscular transfection of the recombinant adenoviral vector suppressed VEGF
      induced inflammatory cell infiltration in matrigel plugs. When given
      intracerebrally to EAE rats, recombinant sFlt-1(1-3) adenoviral vector
      significantly reduced disease severity compared to untreated rats. sFlt-1(1-3)
      gene transfer blocked VEGF and greatly reduced the number of cells that express
      VEGF and ED1-positive cells in CNS in EAE rats. This study demonstrates that sFlt
      1(1-3) gene transfer into the brain ameliorates the severity of EAE by inhibiting
      monocyte recruitment in the CNS of dark Agouti rats.

PMID- 18721817
TI  - Lichen metabolites prevent UV light and nitric oxide-mediated plasmid DNA damage
      and induce apoptosis in human melanoma cells.
AB  - In humans both UV-A and UV-B can cause gene mutations and suppress immunity,
      which leads to skin cancer, including melanoma. Inhibition of reactive oxygen
      species (ROS) and reactive nitrogen species (RNS) appears particularly promising
      as ROS and RNS production by both UV-A and UV-B contributes to inflammation,
      immunosuppression, gene mutation and carcinogenesis. We evaluated the effect of
      two lichen compounds, sphaerophorin (depside) and pannarin (depsidone) on pBR322
      DNA cleavage induced by hydroxyl radicals (()OH), and by nitric oxide (NO), and
      their superoxide anion (O(2)(-)) scavenging capacity. In addition, we
      investigated the growth inhibitory activity of these compounds against human
      melanoma cells (M14 cell line). Sphaerophorin and pannarin showed a protective
      effect on plasmid DNA and exhibited a superoxide dismutase like effect. The data
      obtained in cell culture show that these lichen metabolites inhibit the growth of
      melanoma cells, inducing an apoptotic cell death, demonstrated by the
      fragmentation of genomic DNA (COMET and TUNEL Assays) and by a significant
      increase of caspase-3 activity, and correlated, at least in part, to the increase
      of ROS generation, These results confirm the promising biological properties of
      sphaerophorin and pannarin and encourage further investigations on their
      molecular mechanisms.

PMID- 18721818
TI  - 18beta-Glycyrrhetinic acid induces apoptotic cell death in SiHa cells and
      exhibits a synergistic effect against antibiotic anti-cancer drug toxicity.
AB  - Defects in mitochondrial function have been shown to participate in the induction
      of cell death in cancer cells. The present study was designed to assess the toxic
      effect of 18beta-glycyrrhetinic acid against human cervix and uterus tumor cell
      line SiHa cells in relation to the mitochondria-mediated cell-death process and
      evaluate the combined toxic effect of 18beta-glycyrrhetinic acid and anti-cancer
      drugs. 18beta-Glycyrrhetinic acid induced the nuclear damage, changes in the
      mitochondrial membrane permeability, formation of reactive oxygen species and
      depletion of glutathione in SiHa cells. It caused cell death by inducing the
      increase in the pro-apoptotic Bax protein and cytochrome c levels, reduction in
      anti-apoptotic Bcl-2 level, subsequent caspase-3 activation and loss of the
      mitochondrial transmembrane potential. Unlike 18beta-glycyrrhetinic acid, a pro
      compound glycyrrhizin up to 100 microM did not induce cell death and depletion of
      glutathione. Combined treatment of mitomycin c (or doxorubicin) and 18beta
      glycyrrhetinic acid revealed a synergistic toxic effect. Meanwhile, combination
      of camptothecin and 18beta-glycyrrhetinic acid exhibited an additive cytotoxic
      effect. Results suggest that 18beta-glycyrrhetinic acid may cause cell death in
      SiHa cells by inducing the mitochondrial membrane permeability change, leading to
      cytochrome c release and caspase-3 activation. The effect may be associated with
      increased formation of reactive oxygen species and depletion of glutathione.
      Combined treatment of antibiotic anti-cancer drug and 18beta-glycyrrhetinic acid
      seems to exhibit a synergistic toxic effect.

PMID- 18721819
TI  - Computational methods for yeast prion curing curves.
AB  - If the chemical guanidine hydrochloride is added to a dividing culture of yeast
      cells in which some of the protein Sup35p is in its prion form, the proportion of
      cells that carry replicating units of the prion, termed propagons, decreases
      gradually over time. Stochastic models to describe this process of 'curing' have
      been developed in earlier work. The present paper investigates the use of
      numerical methods of Laplace transform inversion to calculate curing curves and
      contrasts this with an alternative, more direct, approach that involves numerical
      integration. Transform inversion is found to provide a much more efficient
      computational approach that allows different models to be investigated with
      minimal programming effort. The method is used to investigate the robustness of
      the curing curve to changes in the assumed distribution of cell generation times.
      Matlab code is available for carrying out the calculations.

PMID- 18721820
TI  - Low-frequency blood flow oscillations in congestive heart failure and after beta1
      blockade treatment.
AB  - Laser Doppler flowmetry (LDF) of forearm skin blood flow, combined with
      iontophoretically-administered acetylcholine and sodium nitroprusside and wavelet
      spectral analysis, was used for noninvasive evaluation of endothelial function in
      17 patients newly diagnosed with New York Heart Association class II-III
      congestive heart failure (CHF). After 20+/-10 weeks' treatment with a beta(1)
      blocker (Bisoprolol), the measurements were repeated. Measurements were also made
      on an age- and sex-matched group of healthy controls (HC). In each case data were
      recorded for 30 min. In HC, the difference in absolute spectral amplitude of LDF
      oscillations between the two vasodilators manifests in the frequency interval
      0.005-0.0095 Hz (p<0.01); this difference is initially absent in patients with
      CHF, but appears following the beta(1)-blocker treatment (p<0.01). For HC, the
      difference between the two vasodilators also manifests in normalised spectral
      amplitude in 0.0095-0.021 Hz (p<0.05). This latter difference is absent in CHF
      patients and is unchanged by treatment with beta(1)-blockers. It is concluded
      that there are two oscillatory skin blood flow components associated with
      endothelial function. Both are reduced in CHF. Activity in the lower frequency
      interval is restored by beta(1)-blocker treatment, confirming the association
      between CHF and endothelial dysfunction but suggesting the involvement of two
      distinct mechanisms.

PMID- 18721821
TI  - TIMP-2 disrupts FGF-2-induced downstream signaling pathways.
AB  - We have previously reported that tissue inhibitor of metalloproteinases-2 (TIMP
      2), an endogenous inhibitor of matrix metalloproteinase, modulates angiogenic
      responses through the MMP inhibition-independent activity. In this study, we
      investigate the molecular mechanisms of TIMP-2-mediated growth inhibition in
      response to fibroblast growth factor-2 (FGF-2). Pre-treatment with a protein
      tyrosine phosphatase inhibitor orthovanadate or expression of a dominant negative
      Shp-1 mutant fails to induce TIMP-2 inactivation of FGF-2 signaling pathways in
      human microvascular endothelial cells. We also show that TIMP-2 inhibition of FGF
      2-induced p42/44(MAPK) activation and cell proliferation is associated with TIMP
      2 binding to integrin alpha3beta1 on endothelial cell surfaces, as demonstrated
      by use of anti-integrin alpha3 or beta1 blocking antibodies, or disruption of
      integrin alpha3 expression by siRNA. Collectively, our results indicate that TIMP
      2 inhibits FGF-2 signaling pathways through association with integrin alpha3beta1
      and Shp-1-dependent inhibition of p42/44(MAPK) signaling, which in turn, results
      in suppression of FGF-2-stimulated endothelial cell mitogenesis.

PMID- 18721822
TI  - Native glycine receptor subtypes and their physiological roles.
AB  - The glycine receptor chloride channel (GlyR), a member of the pentameric Cys-loop
      ion channel receptor family, mediates inhibitory neurotransmission in the spinal
      cord, brainstem and retina. They are also found presynaptically, where they
      modulate neurotransmitter release. Functional GlyRs are formed from a total of
      five subunits (alpha1-alpha4, beta). Although alpha subunits efficiently form
      homomeric GlyRs in recombinant expression systems, homomeric alpha1, alpha3 and
      alpha4 GlyRs are weakly expressed in adult neurons. In contrast, alpha2 homomeric
      GlyRs are abundantly expressed in embryonic neurons, although their numbers
      decline sharply by adulthood. Numerous lines of biochemical, biophysical,
      pharmacological and genetic evidence suggest the majority of glycinergic
      neurotransmission in adults is mediated by heteromeric alpha1beta GlyRs.
      Immunocytochemical co-localisation experiments suggest the presence of
      alpha2beta, alpha3beta and alpha4beta GlyRs at synapses in the adult mouse
      retina. Immunocytochemical and electrophysiological evidence also implicates
      alpha3beta GlyRs as important mediators of glycinergic inhibitory
      neurotransmission in nociceptive sensory neuronal circuits in peripheral laminae
      of the spinal cord dorsal horn. It is yet to be determined why multiple GlyR
      synaptic subtypes are differentially distributed in these and possibly other
      locations. The development of pharmacological agents that can discriminate
      strongly between different beta subunit-containing GlyR isoforms will help to
      address this issue, and thereby provide important insights into a variety of
      central nervous system functions including retinal signal processing and spinal
      pain mechanisms. Finally, agents that selectively potentiate different GlyR
      isoforms may be useful as therapeutic lead compounds for peripheral inflammatory
      pain and movement disorders such as spasticity.

PMID- 18721823
TI  - The effects of food viscosity on bite size, bite effort and food intake.
AB  - Two studies investigated the effect of a food's viscosity on bite size, bite
      effort and food intake using a standardized protocol in which subjects sipped
      through a straw every 20 s for a period of 15 min from one of two products, a
      chocolate-flavored dairy drink and a chocolate-flavored dairy semi-solid, matched
      for energy density. In the first study, subjects consumed 47% more from the
      liquid than from the semi-solid to reach the same degree of satiation, with
      larger bite sizes for the liquid throughout the 15 minute period (8.7+/-0.45 g)
      compared to the semi-solid (5.8+/-0.3 g, p<0.01). In the second study bite effort
      was eliminated by using a peristaltic pump to present the products every 20 s.
      Oral processing time before swallowing was set at 5 s (both products) or 8 s
      (semi-solid). With the elimination of bite effort and a standardized oral
      processing time, subjects consumed as much from the semi-solid as from the liquid
      to reach the same degree of satiation. Bite size for liquids started relatively
      small and grew gradually over successive bites, whereas the bite size for the
      semi-solid food started relatively large and became gradually smaller. The latter
      effect was even more pronounced when the oral processing time was increased from
      5 to 8 s. In conclusion, semi-solids resulted in smaller bite sizes and lower
      intake than liquids, but these differences disappeared when differences in bite
      effort were eliminated.

PMID- 18721824
TI  - The p53-mediated cytotoxicity of photodynamic therapy of cancer: recent advances.
AB  - Photodynamic therapy (PDT) is a promising modality for the treatment of both pre
      malignant and malignant lesions. The mechanism of action converges mainly on the
      generation of reactive oxygen species which damage cancer cells directly as well
      as indirectly acting on tumor vasculature. The exact mechanism of PDT action is
      not fully understood, which is a formidable barrier to its successful clinical
      application. Elucidation of the mechanisms of cancer cell elimination by PDT
      might help in establishing highly specific, non-genotoxic anti-cancer treatment
      of tomorrow. One of the candidate PDT targets is the well-known tumor suppressor
      p53 protein recognized as the guardian of the genome. Together with its family
      members, p73 and p63 proteins, p53 is involved in apoptosis induction upon stress
      stimuli. The wild-type and mutant p53-targeting chemotherapeutics are currently
      extensively investigated as a promising strategy for highly specific anti-cancer
      therapy. In photodynamic therapy porphyrinogenic sensitizers are the most widely
      used compounds due to their potent biophysical and biochemical properties. Recent
      data suggest that the p53 tumor suppressor protein might play a significant role
      in porphyrin-PDT-mediated cell death by direct interaction with the drug which
      leads to its accumulation and induction of p53-dependent cell death both in the
      dark and upon irradiation. In this review we describe the available evidence on
      the role of p53 in PDT.

PMID- 18721825
TI  - Ultrasound-guided near-nerve neurography for early evaluation of nerve
      regeneration.
AB  - For early assessment of axonal outgrowth after trauma, the nerve is surgically
      exposed to enable compound nerve action potential (CNAP) recordings across the
      lesion site. Near-nerve neurography, with needle electrodes placed
      transcutaneously near the nerve, could be a minimally invasive alternative if the
      needle placement procedure and low reproducibility are improved. We developed
      ultrasound-guided near-nerve neurography, which facilitates needle placement, and
      assessed its potential for evaluating nerve regeneration. Measurements were
      performed at varying times after crush lesion of the peroneal nerve of 25
      rabbits. To test if ultrasound-guided near-nerve signals could be measured prior
      to muscle reinnervation, they were compared with recordings of compound muscle
      action potentials. A comparison with conventional intra-operative CNAP recordings
      was made by measuring nerve signal amplitude with both techniques and by
      assessing reproducibility. In all cases where intra-operative signals could be
      measured, near-nerve signals were also detected. Compound nerve activity could be
      recorded after 5 weeks, whereas compound muscle activity appeared after
      approximately 8 weeks. Reproducibility was slightly better for near-nerve than
      for intra-operative recordings. We conclude that ultrasound-guided near-nerve
      neurography is able to assess nerve regeneration well before compound muscle
      activity can be detected. Its accuracy and reproducibility are similar to those
      of conventional intra-operative recordings.

PMID- 18721827
TI  - Inhibitory effect of mycophenolic acid on the replication of infectious
      pancreatic necrosis virus and viral hemorrhagic septicemia virus.
AB  - Infectious pancreatic necrosis virus (IPNV) and viral hemorrhagic septicemia
      virus (VHSV) remain two of the most important pathogens of farmed trout
      worldwide. Mycophenolic acid (MPA) is an inhibitor of cellular inosine
      monophosphate dehydrogenase (IMPDH), an enzyme that catalyzes an essential step
      in the biosynthesis of GTP. In this report, the antiviral activity of MPA against
      IPNV and VHSV in cell culture was assessed. Cell viability, virus yield, protein
      and RNA synthesis determinations were used to evaluate the inhibitory effect of
      MPA. MPA caused a dose-dependent inhibition of IPNV and VHSV replication. It was
      found that MPA had a particularly potent effect against IPNV, inhibiting the
      production of infectious virus more than 10(5)-fold. MPA was also highly
      effective in preventing viral protein synthesis. Quantitative real-time RT-PCR
      was used to measure viral RNA in cells infected by IPNV or VHSV to evaluate the
      inhibitory capacity of MPA as well as to compare MPA to the established antiviral
      drug ribavirin. MPA showed a good efficacy in decreasing accumulation of viral
      RNA at low concentrations. Finally, time of addition and wash out experiments
      suggested that MPA may have a dual mechanism of action, targeting both a cell and
      a viral function. This study provides evidence that MPA can function as a broad
      spectrum antiviral drug for use in therapy of rainbow trout diseases.

PMID- 18721826
TI  - Dopamine receptors in human lymphocytes: radioligand binding and quantitative RT
      PCR assays.
AB  - Analysis of dopamine receptors (DR) in lymphocytes of the human peripheral blood
      mononuclear cell (PBMC) fraction is an attractive tool for evaluation of
      functional properties of dopaminergic function underlying variation in complex
      psychological/psychopathological traits. Receptor binding assays (RBAs) with
      selective radioligands, which are widely used in CNS studies, have not produced
      consistent results when applied to isolated PBMC. We tested the assay conditions
      that could be essential for detection of DR in human PBMC and their membrane
      preparations. Using [(3)H]SCH23390, a dopamine D1-like receptor antagonist, we
      demonstrated the presence of two binding sites in PBMC-derived membrane fraction.
      One of them is characterized by the K(d) value consistent with that reported for
      D5 dopamine receptors in human lymphocytes, whereas the other K(d) value possibly
      corresponds to serotonin receptor(s). Although D5 receptor binding sites in PBMC
      membranes could be characterized by binding assays, the low protein expression
      and the large volume of blood needed for membrane preparation render the binding
      method impracticable for individual phenotyping. In contrast, real-time RT-PCR
      may be used for this purpose, contingent on the relationship between DR
      expression in the brain and in lymphocytes. The expression of the DRD2-DRD5
      genes, as detected by this method, varied widely among samples, whereas the DRD1
      expression was not detected. The expression levels were comparable with those in
      the brain for DRD3 and DRD4, and were significantly lower for DRD2 and DRD5.

PMID- 18721828
TI  - Genetic influences on hippocampal structure and function in recombinant inbred
      mice.
AB  - Previously, we identified separate genetic influences on ventral versus dorsal
      hippocampal volume in BXD recombinant inbred mice [Martin MV, Dong HX, Vallera D,
      Lu L, Williams RW, Rosen GD, et al. Independent quantitative trait loci influence
      ventral and dorsal hippocampal volume in recombinant inbred strains of mice.
      Genes Brain Behav 2006;5:614-23]. Based on genotype at genetic markers associated
      with ventral hippocampal volume, we evaluated BXD mouse strains with relatively
      small versus large ventral hippocampal volumes using numerous behavioral
      paradigms known to rely upon hippocampal function and several other tasks that
      tap into behaviors analogous to those often impaired in schizophrenia. We
      observed a relationship between genotype at markers known to influence ventral
      hippocampal volume and working memory at an intermediate memory load. There was
      no association between genotype at markers known to influence ventral hippocampal
      volume and spatial reference memory, prepulse inhibition, or elevated plus maze
      performance. The relevance of these findings for understanding the
      pathophysiology of schizophrenia are discussed, including the possibility that
      genetic predisposition toward anterior hippocampal volume reductions and working
      memory deficits in schizophrenia may be related through a shared genetic locus.

PMID- 18721830
TI  - EEG oscillations induced by contour closure in a noisy visual field.
AB  - This study was designed to separate the neural response associated with awareness
      of a visual object from the neural responses to the visual input without
      awareness. Two classes of stimuli were presented to subjects: (1) a field of
      randomly positioned and oriented Gabor patches (no contour) or (2) the same field
      of Gabor patches in which a subset of the Gabor patches were oriented in such a
      way as to give rise to the percept of an ellipse (contour). To measure the
      electroencephalograph (EEG) responses to the contour without awareness, trials
      during which a contour was present but not perceived were compared to trials
      where no contour was present and its absence was correctly indicated. At beta
      frequencies, the presence of the contour reduced the evoked potential (EP) power
      approximately 130-230 ms post-stimulus. Coherence in the theta band were also
      reduced when a contour was present but not perceived. Thus, modulations of the EP
      take place when a contour is presented even without the subjects' awareness. To
      explore the correlates of awareness, trials during which the subject correctly
      indicated the presence of a contour were compared to trials in which the object
      was not detected. Consistent across subjects, awareness caused an increase in the
      EP power in the beta range around 130-230 ms post-stimulus. These results suggest
      that the neural response to an object and awareness of that object are
      dissociable in EEG recordings.

PMID- 18721829
TI  - Delta 9-tetrahydrocannabinol suppresses vomiting behavior and Fos expression in
      both acute and delayed phases of cisplatin-induced emesis in the least shrew.
AB  - Cisplatin chemotherapy frequently causes severe vomiting in two temporally
      separated clusters of bouts dubbed the acute and delayed phases. Cannabinoids can
      inhibit the acute phase, albeit through a poorly understood mechanism. We
      examined the substrates of cannabinoid-mediated inhibition of both the emetic
      phases via immunolabeling for serotonin, Substance P, cannabinoid receptors 1 and
      2 (CB(1), CB(2)), and the neuronal activation marker Fos in the least shrew
      (Cryptotis parva). Shrews were injected with cisplatin (10mg/kg i.p.), and one of
      vehicle, Delta(9)-THC, or both Delta(9)-THC and the CB(1) receptor antagonist
      SR141716A (2mg/kg i.p.), and monitored for vomiting. Delta(9)-THC-pretreatment
      caused concurrent decreases in the number of shrews expressing vomiting and Fos
      immunoreactivity (Fos-IR), effects which were blocked by SR141716A-pretreatment.
      Acute phase vomiting induced Fos-IR in the solitary tract nucleus (NTS), dorsal
      motor nucleus of the vagus (DMNX), and area postrema (AP), whereas in the delayed
      phase Fos-IR was not induced in the AP at all, and was induced at lower levels in
      the other nuclei when compared to the acute phase. CB(1) receptor-IR in the NTS
      was dense, punctate labeling indicative of presynaptic elements, which surrounded
      Fos-expressing NTS neurons. CB(2) receptor-IR was not found in neuronal elements,
      but in vascular-appearing structures. All areas correlated with serotonin- and
      Substance P-IR. These results support published acute phase data in other
      species, and are the first describing Fos-IR following delayed phase emesis. The
      data suggest overlapping but separate mechanisms are invoked for each phase,
      which are sensitive to antiemetic effects of Delta(9)-THC mediated by CB(1)
      receptors.

PMID- 18721831
TI  - Chromogranin peptides in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder which
      primarily affects motor neurons. Eight cases of ALS and seven control cases were
      studied with semiquantitative immunocytochemistry for chromogranin A,
      chromogranin B and secretogranin II that are soluble constituents of large dense
      core vesicles, synaptophysin as a membrane protein of small synaptic vesicles and
      superoxide dismutase 1. Among the chromogranin peptides, the number and staining
      intensity of motor neurons was highest for chromogranin A. In ALS, the staining
      intensity for chromogranin peptides and synaptophysin was significantly lower in
      the ventral horn of ALS patients due to a loss in immunoreactive motor neurons,
      varicose fibers and varicosities. For all chromogranins, the remaining motor
      neurons displayed a characteristic staining pattern consisting of an
      intracellular accumulation of immunoreactivity with a high staining intensity.
      Confocal microscopy of motor neurons revealed that superoxide dismutase 1
      immunopositive intracellular aggregates also contained chromogranin A,
      chromogranin B and secretogranin II. These findings indicate that there is a loss
      of small and large dense core vesicles in presynaptic terminals. The
      intracellular co-occurrence of superoxide dismutase 1 and chromogranins may
      suggest a functional interaction between these proteins. This study should prompt
      further experiments to elucidate the role of chromogranins in ALS patients.

PMID- 18721832
TI  - FISH-eyed and genome-wide views on the spatial organisation of gene expression.
AB  - Eukaryotic cells store their genome inside a nucleus, a dedicated organelle
      shielded by a double lipid membrane. Pores in these membranes allow the exchange
      of molecules between the nucleus and cytoplasm. Inside the mammalian cell
      nucleus, roughly 2 m of DNA, divided over several tens of chromosomes is packed.
      In addition, protein and RNA molecules functioning in DNA-metabolic processes
      such as transcription, replication, repair and the processing of RNA fill the
      nuclear space. While many of the nuclear proteins freely diffuse and display a
      more or less homogeneous distribution across the nuclear interior, some appear to
      preferentially cluster and form foci or bodies. A non-random structure is also
      observed for DNA: increasing evidence shows that selected parts of the genome
      preferentially contact each other, sometimes even at specific sites in the
      nucleus. Currently a lot of research is dedicated to understanding the functional
      significance of nuclear architecture, in particular with respect to the
      regulation of gene expression. Here we will evaluate evidence implying that the
      folding of DNA is important for transcriptional control in mammals and we will
      discuss novel high-throughput techniques expected to further boost our knowledge
      on nuclear organisation.

PMID- 18721833
TI  - BioTimer Assay, a new method for counting Staphylococcus spp. in biofilm without
      sample manipulation applied to evaluate antibiotic susceptibility of biofilm.
AB  - The medical device-related infections are frequently a consequence of
      Staphylococcus biofilm, a lifestyle enhancing bacterial resistance to
      antibiotics. Antibiotic susceptibility tests are usually performed on planktonic
      forms of clinical isolates. Some methods have been developed to perform
      antibiotic susceptibility tests on biofilm. However, none of them counts
      bacterial inoculum. As antibiotic susceptibility is related to bacterial
      inoculum, the test results could be mistaken. Here, a new method, BioTimer Assay
      (BTA), able to count bacteria in biofilm without any manipulation of samples, is
      presented. Moreover, the BTA method is applied to analyze antibiotic
      susceptibility of six Staphylococcus strains in biofilm and to determine the
      number of viable bacteria in the presence of sub-inhibitory doses of four
      different antibiotics. To validate BTA, the new method was compared to reference
      methods both for counting and antibiotic susceptibility tests. A high agreement
      between BTA and reference methods is found on planktonic forms. Therefore, BTA
      was employed to count bacteria in biofilm and to analyze biofilm antibiotic
      susceptibility. Results confirm the high resistance to antibiotics of
      Staphylococcus biofilm. Moreover, BTA counts the number of viable bacteria in the
      presence of sub-inhibitory doses of antibiotics. The results show that the number
      of viable bacteria depends on sub-inhibitory doses, age of biofilm and type of
      antibiotic. In particular, differently to gentamicin and ampicillin, sub
      inhibitory doses of ofloxacin and azithromycin reduce the number of viable
      bacteria at lower extent in young than in old biofilm. In conclusion, BTA is a
      reliable, rapid, easy-to-perform, and versatile method, and it can be considered
      a useful tool to analyze antibiotic susceptibility of Staphylococcus spp. in
      biofilm.

PMID- 18721834
TI  - Optimization of the expression of hepatitis B virus e gene in Pichia pastoris and
      immunological characterization of the product.
AB  - Escherichia coli-derived hepatitis B e antigen (HBeAg) is widely used for
      serological tests of hepatitis B virus (HBV). Because it exhibits cross
      reactivity with HBcAb in human sera, current antibody to HBeAg (HBeAb)
      immunoassays are based on competitive inhibition enzyme-linked immunosorbent
      assay (ELISA) rather than sandwich ELISA, which interfere with the specificity
      and sensitivity of HBeAb detection. Pichia pastoris has advantages of eukaryotic
      cells, while having the capacity of high-level secretion of foreign proteins. To
      explore the diagnostic suitability of recombinant HBeAg (rHBeAg), we expressed
      the wild type HBV e gene (wt-e-gene) and the synthetic HBV e gene (syn-e-gene;
      native HBV e gene modified based on synonymous codon usage bias) in P. pastoris.
      The recombinant antigen was secreted into the medium. The expression level of
      rHBeAg was enhanced by optimizing HBV e gene. The yield of syn-e-gene product was
      approximately five-fold greater than wt-e-gene. The protein represented 66% of
      the total supernatant protein, and was simply purified to 90%. P. pastoris
      derived HBeAg showed high HBe antigenicity, while lacking any HBc antigenicity
      and cross-reactivity between all proteins derived from the culture of P. pastoris
      and normal human sera. P. pastoris-derived HBeAg has higher specificity and
      sensitivity for detection HBeAb in the diagnostic assay than the commercial HBeAb
      ELISA kits.

PMID- 18721836
TI  - Exaggerated feedback control decreases brain serotonin concentration and elicits
      hyperactivity in a rat model of diet-restriction-induced anorexia nervosa.
AB  - 5-Hydroxytryptamine (5-HT; serotonin) system is the major neurotransmitter system
      of interest in research on anorexia nervosa (AN). The AN patients show extreme
      dieting weight loss, hyperactivity and low basal levels of 5-hydroxyindoleacetic
      acid (5-HIAA), a major metabolite of 5-HT in the cerebrospinal fluid (CSF).
      Studies on animal models show that diet restriction (DR) decreases 5-HT
      metabolism in the brain and hypothalamus which is not necessarily associated with
      a decrease in the availability of essential amino acid tryptophan (TRP) the
      precursor of serotonin. To further investigate the mechanism involved in DR
      induced decreases of 5-HT the present study uses 8-hydroxy-(2-di-n-propylamino)
      tetralin (8-OH-DPAT), a selective 5-HT-1A agonist, as a probe to monitor the
      responsiveness of negative feedback control over 5-HT metabolism. Effects of DR
      and of 8-OHDPAT on TRP, 5-HT and 5-HIAA concentrations are determined in the
      hypothalamus, a region of the brain known to role in the regulation of appetite.
      Animals of DR group given access to food 2h daily for 6 days exhibited 21.6%
      decrease in the body weight compared to freely feeding (FF) controls. The levels
      of TRP in the plasma and of 5-HT in the hypothalamus decreased. No effect was
      found on the levels of TRP in the hypothalamus. 8-OH-DPAT-induced decreases of 5
      HT and 5-HIAA were greater in DR than FF group. 8-OH-DPAT-induced hyperactivity
      was also greater in DR than FF group. The results show that DR-induced decreases
      of 5-HT are due to an increase in the responsiveness of negative feedback control
      over 5-HT and not due to smaller availability of TRP. DR-induced increase in
      activity and 8-OH-DPAT-induced greater hyperactivity in DR than FF group may also
      be due to exaggerated negative feedback control over 5-HT. It is suggested that
      drugs decreasing the responsiveness of negative feedback control over 5-HT may be
      of use for the treatment and prevention of AN in under weight patients on
      restricted diet.

PMID- 18721835
TI  - Release of a model protein from biodegradable self assembled films for surface
      delivery applications.
AB  - Layer-by-layer (LbL) films have multiple features that make them attractive for
      drug delivery, including the potential to sequentially deliver growth factors
      from implantable medical devices or tissue engineering scaffolds. To date,
      however, characterization has been lacking for protein delivery from such films.
      Here, LbL polyelectrolyte films constructed with the model protein lysozyme and a
      hydrolytically degradable and biocompatible synthetic polycation are
      characterized. Milligram/cm(2) scale linear or power law release profiles can be
      achieved over 2 to 34 days, and control over loading and release are demonstrated
      through parameters such as tuning the degradability of the synthetic polycation,
      changing the number of layers used, or changing the polysaccharide polyanion.
      Functionality is maintained at nearly 100%, underscoring mild processing
      conditions apt to preserve fragile protein function. LbL films thus have promise
      as a tool for exploring protein modulation of the interaction between implanted
      surfaces and the cells they contact.

PMID- 18721837
TI  - Scope and limitations of the designer proline-rich antibacterial peptide dimer,
      A3-APO, alone or in synergy with conventional antibiotics.
AB  - The proline-rich antimicrobial peptide dimer, A3-APO, was designed based on a
      statistical analysis of native antibacterial peptide and protein sequences.
      Analysis of a series of structural analogs failed to identify any single or
      multiple amino acid modification or architectural changes that would
      significantly improve its potential as a clinical therapeutic. However, a single
      chain Chex1-Arg20 version, a natural in vivo metabolite, showed a 2 to 8-fold
      increase in activity against test Enterobacteriaceae strains. In addition to
      bacterial species close to Escherichia coli in phylogeny, A3-APO analogs were
      able to effectively kill Pseudomonas aeruginosa and Staphylococcus saprophyticus.
      Antibacterial efficacy analysis together with biochemical experiments provided
      further evidence for a multiple mode of action of A3-APO that includes binding
      and inhibition of the bacterial heat shock protein DnaK. Through inactivating of
      resistance enzymes, A3-APO was able to recover the lost activity of conventional
      antibiotics including chloramphenicol, beta-lactams, sulfonamides or trimethoprim
      against multidrug resistant strains with partial or full synergy. However, the
      synergy appeared to be individual strain and small molecule drug combination
      dependent.

PMID- 18721838
TI  - Influenza vaccination coverage in patients with cystic fibrosis followed at 12
      care centers in the Greater South Region of France for the season 2005/2006.
AB  - The objective of this observational study was to estimate influenza vaccination
      coverage for the 2005/2006 season in cystic fibrosis (CF) patients consulting at
      or hospitalized in 12 CF care centers. Data from 518 CF patients >6 months of age
      (children: 64.9%) were analyzed: 79.9% were vaccinated. The vaccination coverage
      was 85.6% in children, 69.4% in adults and 44.4% in transplanted patients.
      General practitioners vaccinated 67.9% of the patients. "Lack of time" reason was
      reported by 24.7% non-vaccinated patients. In France, influenza vaccination
      coverage in CF patients meets the National Health objective (> or =75% by 2008),
      but could be improved in adults and transplanted patients.

PMID- 18721839
TI  - Efficacy and safety of a live canine adenovirus-vectored rabies virus vaccine in
      swine.
AB  - Rabies infections in swine have been reported occasionally in recent years in
      certain geographic locations. Although a protective vaccine consisting of
      inactivated rabies virus is available for use in swine, searching for a more
      economically viable formulation for use in developing countries is always a
      priority. This work describes the testing of a canine adenovirus that expresses a
      rabies viral epitope (CAV-2-E3Delta-RGP) in a porcine rabies model. The data
      presented here show that the recombinant viral vaccine was effective in
      protecting swine against rabies if administered intramuscularly, but not orally
      or intranasally, and that protection was probably related to the development of a
      humoral response that lasted at least 28 weeks. Following vaccination, no
      behavioral abnormalities were observed in vaccinated swine and virus particles
      were not detected in either tissues or body fluids, indicating that this
      formulation was safe. The recombinant virus stimulated an effective level of
      antibody response in the immunized swine after a single intramuscular
      inoculation.

PMID- 18721840
TI  - Pre-bled-young-rats in genotoxicity testing: a model for peripheral blood
      micronucleus assay.
AB  - Previously we have reported that prior bleeding increases the sensitivity of
      micronucleus (MN) assay in rats (Vikram et al., 2007 a). Rat peripheral blood
      micronucleus (PBMN) assay is generally not considered as reliable method for the
      assessment of clastogenic potential of test chemicals due to selective
      elimination of micronucleated cells from the circulation. The present study is
      aimed to evaluate the sensitivity of pre-bled-young-rat model in detecting
      genotoxins having different mechanism of action. In the present study, young male
      Sprague-Dawley (SD) rats (21-24 days old, weighing 60+/-5 g) and swiss mice (24
      28 days old, weighing 15+/-2g) were used. Streptozotocin (STZ, 50mg/kg),
      Methotrexate (MTX, 10mg/kg), N-nitrosodiethylamine (DEN, 200mg/kg), Quercetin
      (QC, 50mg/kg) and Zidovudine (AZT, 400mg/kg) were used in the present experiment.
      Effect of prior bleeding time (0, 2, 6, 12 and 24h) on the kinetics of MN
      formation with STZ and AZT was studied and 36 h post chemical exposure was found
      to be the most suitable time point for sample collection if prior bleeding time
      was 0, 2 and 6h. Further, the impact of prior bleeding (2h) on the kinetics of MN
      formation in the bone marrow was evaluated with STZ and maximum MN frequency was
      observed after 24h. The area under curve (AUC) analysis proves that prior
      bleeding leads to significant increase in the incidence of micronucleated
      reticulocytes (RETs) in the peripheral blood as compared to respective non-bled
      controls. Out of five tested chemicals AZT and STZ induced significant increase
      in the MN frequency in non-bled animals while at the same dose MTX, AZT, QC and
      STZ induced significant increase in MN frequency in the pre-bled-young-rats
      employing PBMN assay as the end point. Positive results with MTX, AZT, QC, STZ
      and negative results with DEN demonstrate both the sensitivity and specificity of
      pre-bled-young-rat model in the screening of chemicals for genotoxicity using
      PBMN assay as the end point.

PMID- 18721841
TI  - Augmentation of antigen-stimulated allergic responses by a small amount of
      trichloroethylene ingestion from drinking water.
AB  - In previous report, we have shown that trichloroethylene (TCE) increases
      histamine release and inflammatory cytokine production from antigen-stimulated
      mast cells. In this study, we examined the enhancing effect of a small amount of
      TCE ingestion from drinking water on antigen-stimulated allergic responses. After
      exposure of Wistar rats to TCE ingestion for 2 or 4 weeks, we performed a passive
      cutaneous anaphylaxis (PCA) reaction. TCE ingestion for 2 and 4 weeks enhanced
      PCA reaction in a dose-dependent manner. On histological examination, TCE
      ingestion for 2 weeks exacerbated inflammation characterized by infiltration of
      lymphocytes and accumulation of mast cells around the vessel in the skin. After
      TCE ingestion for 4 weeks, the mesenteric lymph nodes (MLNs) showed increase of
      the size and wet weight, and germinal centers changed distinctly. The interleukin
      4 (IL-4) mRNA levels on spleen, MLNs and leukocytes were increased. Moreover,
      serum total IgE levels of TCE ingestion increased in a time-dependent manner. Our
      results suggest that TCE ingestion induces pro-inflammatory responses and causes
      Th1/Th2-type helper T-cell imbalance. And more, a small amount of TCE ingestion
      may lead to the initiation and acceleration of type I allergic reaction.

PMID- 18721842
TI  - Effects of haloperidol and risperidone on the expression of heat shock protein 70
      in MK-801-treated rat C6 glioma cells.
AB  - Non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists such as
      dizocilpine (MK-801) produce schizophrenia-like psychosis in humans and induce
      the expression of heat shock protein 70 (HSP70) in rats. The present study
      examines the effects of antipsychotic drugs, haloperidol and risperidone, on the
      expression of HSP70 produced by MK-801 in rat C6 glioma cells. After pretreating
      with haloperidol and risperidone for 1 h, 6 h, 24 h and 72 h, respectively, C6
      glioma cells were cultivated again in MK-801 for 6 h, and then, the extent of
      HSP70 expression was measured by immunoblotting using anti-HSP70 monoclonal
      antibody. The expression of HSP70 induced by MK-801 significantly decreased as
      the duration of haloperidol pretreatment was extended (p=0.002). Risperidone also
      increasingly attenuated the expression of HSP70 produced by MK-801 as the
      duration of pretreatment grew longer (p=0.003). The present findings show that
      haloperidol and risperidone decrease the HSP70 expression in MK-801-treated rat
      C6 glioma cells. These results suggest that HSP70 and NMDA receptors may play a
      significant role in the pathophysiology of schizophrenia.

PMID- 18721843
TI  - Patterns of mood changes throughout the reproductive cycle in healthy women
      without premenstrual dysphoric disorders.
AB  - OBJECTIVE: The cyclic nature of female reproductive function is a natural part of
      life accompanied by changes in several physical and psychological phenomena. The
      aim of our study was to investigate the fluctuation of psychological symptoms
      throughout the female reproductive cycle in healthy, non-PMDD (premenstrual
      dysphoric disorder) women. METHOD: 63 psychiatrically healthy, non-PMDD women
      with normal regular menstrual cycles and not using hormonal contraceptive methods
      participated in the study. Participants completed the PRISM (Prospective Record
      of the Impact and Severity of Menstrual Symptoms) calendar every night for three
      cycles and in addition they completed several other psychometric measures
      (Symptom Distress Checklist-SCL-51, State Trait Anxiety Inventory-STAI, Zung Self
      rating Depression Scale-ZSDS, Eating Attitude Test-EAT, Mind and Body Cathexis
      Scale) at three predefined days of the first cycle. Based on an at least 66%
      increase in physical symptoms from the late follicular to the late luteal phase
      on the PRISM, subjects were assigned to luteal phase physical symptoms (LPPS) and
      no luteal phase physical symptoms (nonLPPS) groups. The association of
      psychometric scores with timing within the cycle and with physical symptoms was
      analysed. RESULTS: Significant changes in psychometric scores over time were
      observed for STAI state anxiety, SCL anxiety, SCL somatization, SCL depression,
      SCL obsessive-compulsive, SCL interpersonal sensitivity, SCL total, and ZSDS. A
      significant timexLPPS grouping interaction emerged in case of the SCL
      somatization subscale and the ZSDS. LPPS grouping was associated with only the
      interpersonal sensitivity subscale of the SCL51. CONCLUSION: Our results indicate
      that there is a significant increase in psychological symptoms related to
      neuroticism and depression from the late follicular to the late luteal phase in a
      healthy, non-PMDD female population. Although our results may not have direct
      clinical significance, since the statistically significant increases in
      psychometric scores are still small, it is an important finding that there is a
      consistent pattern observable in the fluctuation of psychological symptoms
      accompanying the female reproductive cycle.

PMID- 18721844
TI  - Lack of evidence to support the glyoxalase 1 gene (GLO1) as a risk gene of autism
      in Han Chinese patients from Taiwan.
AB  - PURPOSE: Previous studies have revealed inconsistent findings regarding the
      association between the glyoxalase 1 protein (GLO1) gene and autism. This study
      aimed to replicate the genetic association of the C419A of the GLO1 gene with
      autism and to perform mutation screening of all the exons of the GLO1 gene in a
      sample of Han Chinese patients with autism from Taiwan. METHODS: The sample
      included 272 patients with autism and 310 healthy controls. All the exons and the
      promoter region of the GLO1 gene were PCR-amplified and sequenced for mutation
      screening and genotyping. RESULTS: We did not find significant differences of
      allelic and genotypic frequency distributions of C419A between the autism and
      control groups. Moreover, we did not identify any other mutations in the exon
      regions associated with autism in this sample. We discovered two single
      nucleotide polymorphisms (SNPs) at the 5' untranslated region of the GLO1 gene,
      designated g.-264T/G and g.-7T/C; however, these two SNPs were not associated
      with autism in this sample. Further analysis of halplotypes constructed from
      these 3 SNPs (g.-264T/G, g.-7T/C, and C419A) found no haplotype associated with
      autism. Our sample size has the power of 0.57 and 0.94 to detect a small effect
      (0.1) in the genotype and allele frequency distributions at the alpha level of
      0.05, respectively. CONCLUSIONS: Our findings suggest that the GLO1 gene is
      unlikely a major susceptible gene for autism in an ethnic Chinese population from
      Taiwan.

PMID- 18721846
TI  - Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde.
AB  - Formaldehyde (FA) is a chemical traditionally used in pathology and anatomy
      laboratories as a tissue preservative. Several epidemiological studies of
      occupational exposure to FA have indicated an increased risk of nasopharyngeal
      cancers in industrial workers, embalmers and pathology anatomists. There is also
      a clear evidence of nasal squamous cell carcinomas from inhalation studies in the
      rat. The postulated mode of action for nasal tumours in rats was considered
      biologically plausible and considered likely to be relevant to humans. Based on
      the available data IARC, the International Agency for Research on Cancer, has
      recently classified FA as a human carcinogen. Although the in vitro genotoxic as
      well as the in vivo carcinogenic potentials of FA are well documented in
      mammalian cells and in rodents, evidence for genotoxic effects and carcinogenic
      properties in humans is insufficient and conflicting thus remains to be more
      documented. To evaluate the genetic effects of long-term occupational exposure to
      FA a group of 30 Pathological Anatomy laboratory workers was tested for a variety
      of biological endpoints, cytogenetic tests (micronuclei, MN; sister chromatid
      exchange, SCE) and comet assay. The level of exposure to FA was evaluated near
      the breathing zone of workers, time weighted average of exposure was calculated
      for each subject. The association between the biomarkers and polymorphic genes of
      xenobiotic metabolising and DNA repair enzymes was also assessed. The mean level
      of exposure was 0.44+/-0.08ppm (0.04-1.58ppm). MN frequency was significantly
      higher (p=0.003) in the exposed subjects (5.47+/-0.76) when compared with
      controls (3.27+/-0.69). SCE mean value was significantly higher (p<0.05) among
      the exposed group (6.13+/-0.29) compared with control group (4.49+/-0.16). Comet
      assay data showed a significant increase (p<0.05) of TL in FA-exposed workers
      (60.00+/-2.31) with respect to the control group (41.85+/-1.97). A positive
      correlation was found between FA exposure levels and MN frequency (r=0.384,
      p=0.001) and TL (r=0.333, p=0.005). Regarding the genetic polymorphisms studied,
      no significant effect was found on the genotoxic endpoints. The results of the
      present biomonitoring study emphasize the need to develop safety programs.

PMID- 18721845
TI  - Pyrazole induced oxidative liver injury independent of CYP2E1/2A5 induction due
      to Nrf2 deficiency.
AB  - Pyrazole can induce CYP2E1 and 2A5, which produce reactive oxygen species (ROS).
      Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates important
      antioxidant enzymes to remove ROS. In this study, we applied Nrf2 knockout mice
      to test the hypothesis that pyrazole will cause hepatotoxicity and elevate
      oxidative stress to a greater extent in Nrf2 knockout mice compared to wild type
      mice. Pyrazole induced severe oxidative liver damage in Nrf2 knockout mice but
      not in wild type mice. Activities and levels of CYP2E1 and 2A5 were elevated by
      pyrazole in the wild type mice but not in the Nrf2 knockout mice. However,
      expression or activity of Nrf2-regulated antioxidant enzymes, such as gamma
      glutamylcysteine synthetase (GCS), heme oxygenase-1 (HO-1) and glutathione-S
      transferase (GST), were upregulated in the pyrazole-treated wild type mice, but
      to a lesser extent or not at all in the pyrazole-treated Nrf2 knockout mice.
      Treatment with antioxidants such as vitamin C or S-adenosyl-l-methionine (SAM) or
      an inhibitor of iNOS prevented the pyrazole-induced oxidative liver damage, thus
      validating the role of oxidative/nitrosative stress in the pyrazole induced liver
      injury to the Nrf2 knockout mice. In summary, even though ROS-producing
      CYP2E1/2A5 were not elevated by pyrazole, impaired antioxidant capacity resulting
      from Nrf2 deficiency appear to be sufficient to promote pyrazole-induced
      oxidative liver injury.

PMID- 18721847
TI  - Association between BDNF Val66Met polymorphism and trait depression is mediated
      via resting EEG alpha band activity.
AB  - A functional polymorphism of the brain-derived neurotrophic factor, BDNF
      Val66Met, is associated with risk for major depression alongside impairments in
      memory and selective attention. This study aims to identify the mediating neural
      mechanisms in links between BDNF and depression using highly heritable
      electroencephalographic (EEG) recordings. In 305 healthy subjects, BDNF Val66Met
      genotypes were compared in terms of trait depression, neural function (EEG during
      a resting state) and cognitive performance. The mediating effects of the EEG
      brain imaging endophenotypes were also examined using structural equation (path)
      modeling. A genotype-endophenotype-phenotype path model showed that Met
      homozygosity predicted elevated working memory commission errors and altered EEG
      activity; that is elevated relative theta and delta power coupled with reduced
      alpha power. In turn, reduced EEG alpha activity mediated the relationship
      between the Met/Met genotype and trait depression. These findings demonstrate the
      utility of an integrative endophenotype approach. They suggest that the BDNF
      Met/Met homozygote has a direct impact on memory systems, but impacts trait
      depression via the secondary effects of neural changes.

PMID- 18721848
TI  - Protein crystal's shape and polymorphism prediction within the limits resulting
      from the exploration of the Miyazawa-Jernigan matrix.
AB  - A computer study of the prediction of the protein crystal's shape and
      polymorphism of crystal's structures within the limits resulting from the
      exploration of the Miyazawa-Jernigan matrix is presented. In this study, a coarse
      graining procedure was applied to prepare a two-dimensional growth unit, where
      instead of full atom representation of the protein a two-type (hydrophobic
      hydrophilic, HP) aminoacidal representation was used. The interaction energies
      between hydrophobic (E(HH)) aminoacids were chosen from the well-known HP-type
      models (E(HH)in[-4,-3,-2.3,-1]), whereas interaction energies between hydrophobic
      and hydrophilic aminoacids (E(HP)) as well as interaction energies between
      hydrophilic aminoacids (E(PP)) were chosen from the range: <-1,1>, but not all
      values from this range fulfiled limitations resulting from the exploration of the
      Miyazawa-Jernigan matrix. Exploring every positively vetted combinations of
      energy interactions a polymorphism of the unit cell was observed what led to the
      fact that different final crystal's shapes were obtained.

PMID- 18721849
TI  - Transport characteristics of molecular motors.
AB  - Properties of transport of molecular motors are investigated. A simplified model
      based on the concept of Brownian ratchets is applied. We analyze a stochastic
      equation of motion by means of numerical methods. The transport is systematically
      studied with respect to its energetic efficiency and quality expressed by an
      effective diffusion coefficient. We demonstrate the role of friction and non
      equilibrium driving on the transport quantifiers and identify regions of a
      parameter space where motors are optimally transported.

PMID- 18721850
TI  - Langmuir-Blodgett based lipase nanofilms of unique structure-function
      relationship.
AB  - Proteins represent versatile building blocks for realization of nanostructured
      materials of unique structure-function relationship to be applied in
      nanobiotechnology. Following a recent work [Bruzzese, D., Pastorino, L.,
      Pechkova, E., Sivozhelezov, Nicolini, C., Increase of catalytic activity of
      lipase towards olive oil by Langmuir-Film Immobilization of Lipase, Enzyme and
      Microbial Technology, submitted for publication.], the Langmuir-Blodgett
      technique was utilized to develop nanostructured crystal materials based on
      enzymes interfacially activated with olive oil as substrate. Particularly, thin
      films of lipase from both Mucor miehei and Candida rugosa were fabricated and
      characterized by UV-vis spectroscopy, Atomic force microscopy and biochemical
      assays. As the first step the M. miehei protein films were studied at the air
      water interface and then transferred onto a solid support for further
      characterization of the enzymatic activity also versus surface pressure, proving
      that Langmuir-Blodgett film provides a better catalytic effect in lipase than a
      mere oil-water boundary. Moreover, improvement of lipase catalytic performance
      was achieved for the M. miehei versus the C. rugosa, despite its almost random
      distribution of hydrophobic patches and the low purity of its preparation.

PMID- 18721851
TI  - Conceptualisation of articular cartilage as a giant reverse micelle: a
      hypothetical mechanism for joint biocushioning and lubrication.
AB  - Phospholipid (PL) molecules form the main structure of the membrane that prevents
      the direct contact of opposing articular cartilage layers. In this paper we
      conceptualise articular cartilage as a giant reverse micelle (GRM) in which the
      highly hydrated three-dimensional network of phospholipids is electrically
      charged and able to resist compressive forces during joint movement, and hence
      loading. Using this hypothetical base, we describe a hydrophilic-hydrophilic (HL
      HL) biopair model of joint lubrication by contacting cartilages, whose mechanism
      is reliant on lamellar cushioning. To demonstrate the viability of our concept,
      the electrokinetic properties of the membranous layer on the articular surface
      were determined by measuring via microelectrophoresis, the adsorption of ions H,
      OH, Na and Cl on phospholipid membrane of liposomes, leading to the calculation
      of the effective surface charge density. The surface charge density was found to
      be -0.08+/-0.002cm(-2) (mean+/-S.D.) for phospholipid membranes, in 0.155M NaCl
      solution and physiological pH. This value was approximately five times less than
      that measured in 0.01M NaCl. The addition of synovial fluid (SF) to the 0.155M
      NaCl solution reduced the surface charge density by 30% which was attributed to
      the binding of synovial fluid macromolecules to the phospholipid membrane. Our
      experiments show that particles charge and interact strongly with the polar core
      of RM. We demonstrate that particles can have strong electrostatic interactions
      when ions and macromolecules are solubilized by reverse micelle (RM). Since ions
      are solubilized by reverse micelle, the surface entropy influences the change in
      the charge density of the phospholipid membrane on cartilage surfaces. Reverse
      micelles stabilize ions maintaining equilibrium, their surface charges contribute
      to the stability of particles, while providing additional screening for
      electrostatic processes.

PMID- 18721852
TI  - Model of two noise source dependent Ornstein-Uhlenbeck processes applied to
      postural sway.
AB  - In this study the postural control system is modeled in terms of two
      counteracting bio-subsystems. Their activities are described by two Ornstein
      Uhlenbeck processes with different-in-magnitude noise sources. The model is
      constructed as a sum of these processes, where in each of them the same noise
      source with opposite sign of the noise coefficients was introduced. Since the
      friction coefficients are also different for these processes, the delay of a
      crossover from ballistic to diffusive motion for one of the subsystems is greater
      than for its counterpart. It turns out that for smaller time intervals a
      superdiffusive behavior is observed, whereas, counteraction of subsystems is
      called into play for a larger time intervals, what for investigated range of
      data, is exhibited as a slow, subdiffusive behavior.

PMID- 18721853
TI  - A diffusive model of the ball and chain inactivation.
AB  - The ball and chain mechanism is a widely accepted theory for the inactivation of
      the Shaker K(+)channel. In this paper we propose a diffusive model that predicts
      a rate of inactivation that is comparable to the experimental measurements.

PMID- 18721854
TI  - Lacunarity as a novel measure of cancer cells behavior.
AB  - An important goal in many branches of science, especially in molecular biology
      and medicine is the quantitative analysis of the structures and their morphology.
      The morphology can be analyzed in many ways, in particular by the fractal
      analysis. Apart from the fractal dimension, an important part of the fractal
      analysis is the lacunarity measurement which, roughly speaking, characterizes the
      distribution of gaps in the fractal: a fractal with high lacunarity has large
      gaps. In this paper, we present an extension of the lacunarity measure to objects
      with nonregular shapes that enables us to provide a successful discrimination of
      cancer cell lines. The cell lines differ in the shape of vacuole (the gaps in
      their body) which is perfectly suited for the lacunarity analysis.

PMID- 18721855
TI  - Lamellar lubrication in vivo and vitro: friction testing of hexagonal boron
      nitride.
AB  - Phospholipid molecules (PLs) in vivo and graphite, molybdenum disulfide, tungsten
      disulfide and hexagonal boron nitride (h-BN) in vitro are good examples of
      frictionless lubricants. PLs and solid materials have the ability to form multi
      bilayer or layered structures similar to lamellate solid. It has been confirmed
      experimentally that PLs as lamellar lubricants protect the surface of joints
      against wear while acting as frictionless lubricant. An experimental study has
      been conducted on the friction properties of h-boron nitride on porous non-full
      journal bearings. The porous non-full journal bearings were a mixture of 97.5
      wt.% Fe and 2.5 wt.% Cu powder, and compressed to a density of 5.9 g/cm(3). The
      porosity of non-full journal bearings were 15.5 and 27.8 wt.% and were
      impregnated with vaseline and vaseline+5 wt.% h-BN. Additionally, the two
      additives SFR NLGI #2 (or SFR 2522) grease and graphite grease were used for
      comparison to h-BN. The tribological tests were performed on a four-ball machine
      under load of 49 daN, and a friction tribotester. The above experiment strongly
      suggested that h-BN has the ability to lubricate under load with very low
      friction coefficient comparable to phospholipids. Relatively low surface energy
      and low adhesion between the crystallites are giving the additives low friction
      coefficient. The results of the experimental studies showed that h-BN as an
      additive in vaseline possesses friction reducing properties, and excellent anti
      wear properties.

PMID- 18721856
TI  - The HSA affinity of warfarin and flurbiprofen determined by fluorescence
      anisotropy measurements of camptothecin.
AB  - The determination of affinity of warfarin and flurbiprofen to human serum albumin
      (HSA) by fluorescence anisotropy measurements of carboxylate form of camptothecin
      (CPT-C) is the subject of this paper. A simple method based on measurements of
      fluorescence anisotropy of CPT-C allows to determine the affinity constant of CPT
      C to HSA by computation of the fraction of bound CPT-C molecules with HSA It was
      observed, that adding of competing drug to plasma significant reduces the rate of
      increase of CPT-C fluorescence anisotropy with increase of albumin concentration
      and, the affinity constant of CPT-C to HSA decreases. The hypothesis of
      interactions between competing drug and CPT-C is presented. The results of these
      studies suggest that CPT-C displaces other drug from protein binding site and the
      degree of this displacement depends on concentration of drug and drug-HSA binding
      affinity. The presented in this paper biosystems research allows to estimate the
      affinity constant of warfarin and flurbiprofen. It was also confirmed that
      despite that most of drugs bind predominantly to Site I or Site II of HSA (only
      one of these sites is high-affinity site), at elevated concentrations, part of
      drug molecules can be bound to low-affinity site of HSA.

PMID- 18721857
TI  - Groel crystal growth and characterization.
AB  - Single crystals of ribosomal proteins obtained for the first time by Langmuir
      Blodgett (LB) nanotemplate confirm earlier findings (Pechkova et al., 2008),
      pointing to a new generation of bionanomaterials of unique structure-function
      relationship. The ribosomal protein phage GroEL was overexpressed in E. coli.
      Since these protein's samples have some difficulties by classical vapour
      diffusion method to yield optimal diffraction quality and order (GroEL), the LB
      nanotemplate method has been applied and compared to the classical method. With
      the thin film nanotemplate method large phage GroEL crystals appeared in few days
      and were subsequently characterized by MALDI-TOF Mass Spectroscopy and by a very
      preliminary X-ray diffraction.

PMID- 18721858
TI  - Cell response in mixtures of surfactant-culture medium--towards a systemic
      approach to cell-based treatments for focal osteoarthritis.
AB  - Osteoarthritis (OA), the most common form of arthritis is a degenerative joint
      disease, which causes severe long-term pain and physical disability. It is
      becoming more important to improve diagnosis and understanding of the disease
      process and subsequently develop new intervention to delay or even reverse the
      disease progress. Our study was designed to combine two relatively novel
      treatment techniques, autologous chondrocyte transplantation (ACT) and proposed
      application of medical remedies based on surface-active phospholipids. To this
      end we exposed chondrocyte to culture environments with mixtures of culture
      medium and phospholipid solutions. Following various culture periods, cell
      survival and well-being were determined by measuring proliferation and assessing
      morphological features, and comparing these with the behaviour of cells grown in
      classical which were not mixed with surfactant, i.e., control culture medium.
      Scanning electron microscopy and light microscopy demonstrate that the cells
      exposed to mixtures with surfactant were as healthy as those in the control
      environment with polygonal morphology, while proliferation assay indicated a
      noticeably higher level of proliferation over similar periods, for cells cultured
      in media that was mixed with surfactants. Also, the cells in media with
      unsaturated surfactants responded better than those cultured in mixtures
      containing saturated surfactant.

PMID- 18721859
TI  - Paraventricular hypothalamic nucleus stimulation modulates nociceptive responses
      in dorsal horn wide dynamic range neurons.
AB  - Effects of different parameters of hypothalamic paraventricular nucleus (PVN)
      electrical stimulation on somatic responses, in dorsal horn neurons were
      examined. In anaesthetized rats, single-unit extracellular recordings were made
      from dorsal horn lumbar segments, which receive afferent input from the toe and
      hind paw regions. We compared the neuronal responses evoked by electrical
      stimulation of the receptive field (RF) with the responses preceded by
      ipsilateral PVN stimulation. Only the responses corresponding to Adelta and C
      fiber activation were inhibited when PVN stimulation was delivered. Fast-evoked
      responses corresponding to Abeta fibers were not modified. The magnitude of
      inhibition depends on the intensity and duration of the PVN stimulation train and
      gradually decreases as the time interval between the PVN and RF stimulations
      increases. The results indicate that PVN modulates nociceptive, but not non
      nociceptive neuronal responses at the spinal cord level, and this modulation
      depends on the parameters of the stimulus utilized to activate PVN neurons.

PMID- 18721860
TI  - Direct interactions between C. elegans RAB-3 and Rim provide a mechanism to
      target vesicles to the presynaptic density.
AB  - Rim is a multi-domain, active zone protein that regulates exocytosis and is
      implicated in vesicle priming and presynaptic plasticity. We recently
      demonstrated that synaptic defects associated with loss of Caenorhabditis elegans
      Rim (termed UNC-10) are accompanied by a reduction in docked vesicles adjacent to
      the presynaptic density. Since Rim is known to interact with the vesicle
      associated GTPase Rab3A, here we asked whether UNC-10-dependent recruitment of
      synaptic vesicles to the presynaptic density was through an UNC-10/Rab-3
      interaction. We first established that C. elegans Rab3 (termed RAB-3) in its GTP
      but not GDP-bound state interacts with UNC-10. We then demonstrated by EM
      analysis that rab-3 mutant synapses exhibit the same vesicle-targeting defect as
      unc-10 mutants. Furthermore, unc-10;rab-3 double mutants phenocopy the targeting
      defects of the single mutants, suggesting UNC-10 and RAB-3 act in the same
      pathway to target vesicles at the presynaptic density. Endogenous release of unc
      10;rab-3 double mutants was similar to that of unc-10 single mutants, but more
      severe than rab-3 mutants, suggesting the common targeting defects are reflected
      by the milder rab-3 release defect. Rim has recently been shown to positively
      regulate calcium influx through direct interactions with calcium channels.
      Consistent with this notion we found UNC-10 colocalized with the calcium channel,
      UNC-2 at C. elegans presynaptic densities and synaptic release in unc-10 and rab
      3 mutants exhibit reduced calcium-sensitivity. Together these results suggest
      that vesicles targeted to the presynaptic density by RAB-3/UNC-10 interactions
      are ideally positioned for efficient calcium-dependent release.

PMID- 18721862
TI  - EEG activity in Carmelite nuns during a mystical experience.
AB  - Mystical experiences relate to a fundamental dimension of human existence. These
      experiences, which are characterized by a sense of union with God, are commonly
      reported across all cultures. To date, no electroencephalography (EEG) study has
      been conducted to identify the neuroelectrical correlates of such experiences.
      The main objective of this study was to measure EEG spectral power and coherence
      in 14 Carmelite nuns during a mystical experience. EEG activity was recorded from
      19 scalp locations during a resting state, a control condition and a mystical
      condition. In the mystical condition compared to control condition, electrode
      sites showed greater theta power at F3, C3, P3, Fz, Cz and Pz, and greater gamma1
      power was detected at T4 and P4. Higher delta/beta ratio, theta/alpha ratio and
      theta/beta ratio were found for several electrode sites. In addition, FP1-C3 pair
      of electrodes displayed greater coherence for theta band while F4-P4, F4-T6, F8
      T6 and C4-P4 pairs of electrodes showed greater coherence for alpha band. These
      results indicate that mystical experiences are mediated by marked changes in EEG
      power and coherence. These changes implicate several cortical areas of the brain
      in both hemispheres.

PMID- 18721861
TI  - Melatonin prevents ischemic brain injury through activation of the mTOR/p70S6
      kinase signaling pathway.
AB  - We previously reported that melatonin prevents neuronal cell death in ischemic
      brain injury through the activation of Akt and the inhibition of apoptotic cell
      death. We investigated whether melatonin inhibits the apoptotic signal through
      the activation of a mammalian target of rapamycin (mTOR) and p70S6 kinase and its
      downstream target, S6 phosphorylation. It is known that mTOR is a downstream
      target of Akt and a central regulator of protein synthesis, cell growth, and cell
      cycle progression. Adult male rats were treated with melatonin (5mg/kg) or
      vehicle prior to middle cerebral artery occlusion (MCAO). Brains were collected
      at 24h after MCAO and infarct volumes were analyzed. We confirmed that melatonin
      significantly reduces infarct volume and decreases the number of TUNEL-positive
      cells in the cerebral cortex. Brain injury induced a decrease in phospho-mTOR and
      phospho-p70S6 kinase. Melatonin prevented the injury-induced decrease in Akt
      activation and phosphorylation of mTOR and p70S6 kinases, and the subsequent
      decrease in S6 phosphorylation. Our results suggest that melatonin prevents cell
      death resulting from ischemic brain injury and that its neuroprotective effects
      are mediated by preventing the injury-induced decrease of mTOR and p70S6 kinase
      phosphorylation.

PMID- 18721863
TI  - Expertise-dependent modulation of muscular and non-muscular torques in multi
      joint arm movements during piano keystroke.
AB  - The problem of skill-level-dependent modulation in the joint dynamics of multi
      joint arm movements is addressed in this study using piano keystroke performed by
      expert and novice piano players. Using the measured kinematic and key-force data,
      the time varying net, gravitational, motion-dependent interaction (INT), key
      reaction (REA), and muscular (MUS) torques at the shoulder, elbow, wrist, and
      metacarpophalangeal (MP) joints were computed using inverse dynamics techniques.
      INTs generated at the elbow and wrist joints, but not those at the MP joint, were
      greater for the experts as compared with the novices. REA at the MP joint, but
      not at the other joints, was less for the experts as compared with the novices.
      The MUSs at the MP, wrist, and elbow joints were smaller, and that at the
      shoulder joint was larger for the experts as compared with the novices. The
      experts also had a lesser inter-strike variability of key striking force and key
      descending velocity as compared with the novices. These findings indicated that
      the relationship among the INT, REA, and MUS occurring at the joints of the upper
      extremity differed between the expert and novice piano players, suggesting that
      the organization of multi-joint arm movement is modulated by long-term motor
      training toward facilitating both physiological efficiency and movement accuracy.

PMID- 18721864
TI  - Forced and voluntary exercise differentially affect brain and behavior.
AB  - The potential of physical exercise to decrease body weight, alleviate depression,
      combat aging and enhance cognition has been well-supported by research studies.
      However, exercise regimens vary widely across experiments, raising the question
      of whether there is an optimal form, intensity and duration of exertion that
      would produce maximal benefits. In particular, a comparison of forced and
      voluntary exercise is needed, since the results of several prior studies suggest
      that they may differentially affect brain and behavior. In the present study, we
      employed a novel 8-week exercise paradigm that standardized the distance,
      pattern, equipment and housing condition of forced and voluntary exercisers.
      Exercising rats were then compared with sedentary controls on measures previously
      shown to be influenced by physical activity. Our results indicate that although
      the distance covered by both exercise groups was the same, voluntary exercisers
      ran at higher speed and for less total time than forced exercisers. When compared
      with sedentary controls, forced but not voluntary exercise was found to increase
      anxiety-like behaviors in the open field. Both forms of exercise increased the
      number of surviving bromodeoxyuridine (BrdU)+ cells in the dentate gyrus after 8
      weeks of exercise, although forced exercisers had significantly more than
      voluntary exercisers. Phenotypic analysis of BrdU+ cells showed no difference
      between groups in the percentage of newborn cells that became neurons, however,
      because forced exercise maximally increased the number of BrdU+ cells, it
      ultimately produced more neurons than voluntary exercise. Our results indicate
      that forced and voluntary exercise are inherently different: voluntary wheel
      running is characterized by rapid pace and short duration, whereas forced
      exercise involves a slower, more consistent pace for longer periods of time. This
      basic difference between the two forms of exercise is likely responsible for
      their differential effects on brain and behavior.

PMID- 18721865
TI  - Age-related expression of calcium/calmodulin-dependent protein kinase II A in the
      hippocampus and cerebral cortex of senescence accelerated mouse prone/8 mice is
      modulated by anti-Alzheimer's disease drugs.
AB  - Senescence-accelerated mouse (SAM) prone/8 (SAMP8) is a good animal model to
      investigate the fundamental mechanisms of age-related learning and memory
      deficits such as Alzheimer's disease (AD) at the gene and protein levels, and SAM
      resistant/1 (SAMR1) is its normal control. Calcium/calmodulin-dependent protein
      kinase II-alpha (CaMKIIalpha) is one of the most abundant subunits of
      calcium/calmodulin-dependent protein kinase II in cerebral cortex and
      hippocampus, and is closely linked to AD. In this study, we used real time
      fluorescence quantitative PCR (RT-PCR) and Western blot techniques to examine the
      expression of CaMKIIalpha mRNA and protein in the cerebral cortex and hippocampus
      of SAMP8 both with aging and following treatment with anti-AD drugs (for example,
      natural product huperzine A (HupA) and traditional Chinese medicinal prescription
      Liu-Wei-Di-Huang decoction (LW), Ba-Wei-Di-Huang decoction (BW), Huang-Lian-Jie
      Du decoction (HL), Dang-Gui-Shao-Yao-San (DSS) and Tiao-Xin-Fang decoction
      (TXF)). The results showed that the levels of both CaMKIIalpha mRNA and protein
      decreased significantly in the cerebral cortex of SAMR1 with aging, but increased
      significantly in the cerebral cortex of SAMP8. Compared with age-matched SAMR1,
      the expression of mRNA and protein of CaMKIIalpha significantly increased in the
      cerebral cortex and hippocampus of SAMP8 after 10 months of age. After SAMP8 was
      treated with the previously mentioned drugs, the abnormally high expression of
      CaMKIIalpha was relatively down-regulated. These results indicated that the
      expression of CaMKIIalpha in the brain of SAMP8 was abnormal and that this
      abnormality could be reversed with anti-AD drugs. These data suggest that
      CaMKIIalpha may play an important role in the age-related cognitive deterioration
      in AD, and may be a potential targets for anti-AD drugs.

PMID- 18721866
TI  - The mitochondrial view of Blastocladiella emersonii.
AB  - The mitochondrial genome of the chytrid Blastocladiella emersonii was sequenced
      and annotated, revealing the complete set of oxidative phosphorylation genes and
      tRNAs/rRNAs necessary for the translation process. Phylogenetic reconstructions
      reinforce the proposal of the new phylum Blastocladiomycota. Evidences of gene
      duplication due to inserted elements suggest shared susceptibility to gene
      invasion/exchange between chytrids and zygomycetes. The gene content of B.
      emersonii is very similar to Allomyces macrogynus but the content of intronic and
      changeable elements is much lower suggesting a stronger resistance to this kind
      of exchange. In addition, a total of 401 potential nuclear transcripts encoding
      mitochondrial proteins were obtained after B. emersonii EST database scanning
      using Saccharomyces cerevisiae, Homo sapiens and Arabidopsis thaliana data as
      probes and TargetP tool to find N-terminal mitochondrial signal in translated
      sequences.

PMID- 18721867
TI  - Cooperative exonization of MaLR and AluJo elements contributed an alternative
      promoter and novel splice variants of RNF19.
AB  - The RNF19 protein, which contains RING-finger and IBR motifs, acts as an E3
      ubiquitin ligase localized to Lewy bodies. RNF19 is located on human chromosome
      8q22.2, has a 4.4-kb transcript, and is ubiquitously expressed in various
      tissues. Here, we identified an alternative RNF19 promoter region and alternative
      RNF19 transcripts derived from MaLR (mammalian apparent LTR-retrotransposon) and
      AluJo elements. Comparative analyses indicated human-specific expression of the
      MaLR- and AluJo-related transcripts. From the expression analysis of 72 tissue
      samples including human normal, tumor, and primate tissues, three different
      isoforms (V1, V2, and V3) of MaLR-derived transcripts were identified.
      Quantitative RT-PCR analysis showed a dominant expression pattern of the V2 MaLR
      derived transcript. A reporter gene assay for MaLR element promoter activity
      indicated that pGL2-RNF19/MaLR in the forward orientation is capable of driving
      luciferase gene expression in Cos7 and HCT116 cells. These findings suggest that
      RNF19 has acquired a new promoter and alternative exons via continuous
      retrotransposition events of MaLR and AluJo elements during mammalian and primate
      evolution, respectively.

PMID- 18721868
TI  - Promoter characterization and regulation of expression of an imprinted gene
      SLC22A18AS.
AB  - The SLC22A18/SLC22A18AS genes are a sense-antisense pair located at human
      chromosome segment 11p15.5. These genes are paternally imprinted: paternal
      alleles are silenced and maternal alleles are expressed. Although SLC22A18 is a
      well-characterized gene, very little is known regarding its antisense partner
      SLC22A18AS. We therefore sought to identify the potential cis-regulating elements
      including the promoter of this gene, differentially methylated regions (DMRs) and
      the translation of its putative ORF. Dual promoters (P1 and P2) were identified
      for this gene and both are devoid of consensus TATA and CCAAT boxes. However, the
      P1 promoter harbors a putative Sp1 binding site. Sp1 binds to the P1 promoter in
      vivo and positively regulates its activity. Promoter and CpG II island regions
      showed heavy methylation of CpG sites, but no DMRs were observed. Treatment of a
      non-SLC22A18AS expressing HuH7 cells with the methyltransferase inhibitor 5-aza
      2'-deoxycytidine restored expression of this gene. The histone deacetylase (HDAC)
      inhibitor Trichostatin-A, on the other hand, failed to induce its expression. We
      suggest that the expression of this gene is methylation-dependent, but histone
      acetylation-independent. This gene was found to be translated with a cytoplasmic
      localization. The present data will help to understand the regulation of this
      gene and its role in tumorigenesis.

PMID- 18721869
TI  - Top-down production of drug nanocrystals: nanosuspension stabilization,
      miniaturization and transformation into solid products.
AB  - During the last 10-15 years, the formulation of drugs as nanocrystals has rapidly
      evolved into a mature drug delivery strategy, with currently five products on the
      market. The major characteristic of these systems is the rapid dissolution
      velocity, enabling bioavailability enhancement after oral administration. This
      mini-review focuses on recent advances with respect to three topics considering
      drug nanocrystals. The first topic is nanosuspension stabilization. A current
      literature status is provided and special attention is given to studies
      attempting to extend our physicochemical understanding of the underlying
      principles. The second part describes recent advances on miniaturization of
      nanosuspension production, to enable formulation screening during preclinical
      development. Finally, literature available on further nanosuspensions
      solidification is discussed, focussing on the maintenance of the preservation of
      the rapid dissolution properties of the nanocrystals after further downstream
      processing.

PMID- 18721870
TI  - Anti-inflammatory and immunosuppressive effect of flavones isolated from
      Artemisia vestita.
AB  - AIM OF THE STUDY: Artemisia vestita is a common traditional Tibetan medicinal
      plant which has been used widely in China for treating various inflammatory
      diseases. Since little is known about its active components, the purpose of this
      study was to isolate and identify the immunosuppressive compounds from Artemisia
      vestita. MATERIALS AND METHODS: A bioassay-guided isolation was performed with
      picryl chloride-induced contact hypersensitivity in mice. MTT assay and Flow
      cytometric analysis were used for determining Con A-induced lymphocyte
      proliferation and CD25 expression in T cells, respectively. RESULTS: The ethanol
      extract of the Artemisia vestita was found to possess significant inhibitory
      activity against the picryl chloride-induced contact hypersensitivity in mice.
      Then 4 fractions were isolated by macroporous adsorption resin and one of these
      fractions (AV3), which showed the highest activity in in vivo test, was further
      subjected to column chromatography. Nine known flavones were isolated and
      identified as pectolinarigenin (1), jaceosidin (2), cirsilineol (3), cirsimaritin
      (4), hispidulin (5), quercetin (6), 6-methoxytricin (7), acacetin (8), and
      apigenin (9). The structures of the 9 flavones were elucidated by spectral
      techniques. All the compounds were evaluated for their inhibitory activity on the
      proliferation and activation of T cells in vitro. Among the 9 flavones,
      cirsilineol (3), 6-methoxytricin (7) and apigenin (9) significantly inhibited T
      cell proliferation and activation in the bioassays. CONCLUSION: The result
      suggests that cirsilineol, 6-methoxytricin and apigenin are the major active
      components in Artemisia vestita.

PMID- 18721871
TI  - Staphylococcal enterotoxin B causes differential expression of Rnd3 and RhoA in
      renal proximal tubule epithelial cells while inducing actin stress fiber assembly
      and apoptosis.
AB  - Staphylococcal enterotoxin B (SEB) is a toxic shock-inducing agent produced by
      Staphylococcus aureus. The hallmark of SEB-induced lethal shock is acute
      vasodilation leading to severe hypotension. Animal studies reveal that
      approximately 70% of intravenously administered toxin localizes to renal proximal
      tubule epithelial cells (RPTEC). This evidence, together with the well-documented
      role of the kidney in regulation of vascular tone, suggests that molecular events
      induced in RPTEC by SEB may contribute to the blood pressure dysregulation seen
      in enterotoxic shock. In an attempt to elucidate these molecular mechanisms,
      differential display was performed on SEB-treated and untreated RPTEC, and 32
      differentially expressed transcripts (DETs) were identified. One of the down
      regulated DETs matched the sequence for Rnd3, which normally inhibits Rho protein
      function. Consistent with Rnd3 down-regulation, message for RhoA was shown to
      increase upon SEB exposure, and actin stress fiber formation was dramatically
      increased. Further, SEB-exposed cells showed both increased enzymatic activity of
      caspase-3 and an increase in the percentage of apoptotic cells. Taken together,
      these results support the hypothesis that RPTEC undergo apoptosis upon exposure
      to SEB. Furthermore, these data implicate the involvement of the Rho family
      proteins in the molecular signaling pathway induced by SEB in RPTEC.

PMID- 18721872
TI  - Development of a set of SNP markers present in expressed genes of the apple.
AB  - Molecular markers associated with gene coding regions are useful tools for
      bridging functional and structural genomics. Due to their high abundance in plant
      genomes, single nucleotide polymorphisms (SNPs) are present within virtually all
      genomic regions, including most coding sequences. The objective of this study was
      to develop a set of SNPs for the apple by taking advantage of the wealth of
      genomics resources available for the apple, including a large collection of
      expressed sequenced tags (ESTs). Using bioinformatics tools, a search for SNPs
      within an EST database of approximately 350,000 sequences developed from a
      variety of apple accessions was conducted. This resulted in the identification of
      a total of 71,482 putative SNPs. As the apple genome is reported to be an ancient
      polyploid, attempts were made to verify whether those SNPs detected in silico
      were attributable either to allelic polymorphisms or to gene duplication or
      paralogous or homeologous sequence variations. To this end, a set of 464 PCR
      primer pairs was designed, PCR was amplified using two subsets of plants, and the
      PCR products were sequenced. The SNPs retrieved from these sequences were then
      mapped onto apple genetic maps, including a newly constructed map of a Royal Gala
      x A689-24 cross and a Malling 9 x Robusta 5, map using a bin mapping strategy.
      The SNP genotyping was performed using the high-resolution melting (HRM)
      technique. A total of 93 new markers containing 210 coding SNPs were successfully
      mapped. This new set of SNP markers for the apple offers new opportunities for
      understanding the genetic control of important horticultural traits using
      quantitative trait loci (QTL) or linkage disequilibrium analysis. These also
      serve as useful markers for aligning physical and genetic maps, and as potential
      transferable markers across the Rosaceae family.

PMID- 18721873
TI  - In cardiac myocytes, cAMP elevation triggers the down-regulation of transcripts
      and promoter activity for cyclic AMP phosphodiesterase-4A10 (PDE4A10).
AB  - Transcripts for the PDE4A10 cyclic AMP phosphodiesterase isoform are present in a
      wide variety of rat tissues including the heart. Sequence comparisons between the
      putative human and mouse promoters revealed a number of conserved regions
      including both an Sp1 and a CREB-binding site. The putative mouse PDE4A10
      promoter was amplified from genomic DNA and sub-cloned into a luciferase reporter
      vector for investigation of activity in neonatal cardiac myocytes. Transfection
      with this construct identified a high level of luciferase expression in neonatal
      cardiac myocytes. Surprisingly, this activity was down-regulated by elevation of
      intracellular cAMP through a process involving PKA, but not EPAC, signalling.
      Such inhibition of the rodent PDE4A10 promoter activity in response to elevated
      cAMP levels is in contrast to the PDE4 promoters so far described. Site-directed
      mutagenesis revealed that the Sp1 binding site at promoter position -348 to -336
      is responsible for the basal constitutive expression of murine PDE4A10. The
      conserved CREB-binding motif at position -370 to -363 also contributes to basal
      promoter activity but does not in itself confer cAMP inhibition upon the PDE4A10
      promoter. EMSA analysis confirmed the authenticity of CREB and Sp1 binding sites.
      The transcriptional start site was identified to be an adenine residue at
      position -55 in the mouse PDE4A10 promoter. We present evidence that this novel
      down-regulation of PDE4A10 is mediated by the transcription factor ICER in a PKA
      dependent manner. The pool of cAMP in cardiac myocytes that down-regulates
      PDE4A10 is regulated by beta-adrenoceptor coupled adenylyl cyclase activity and
      via hydrolysis determined predominantly by the action of PDE4 (cAMP
      phosphodiesterase-4) and not PDE3 (cAMP phosphodiesterase-3). We suggest that
      increased cAMP may remodel cAMP-mediated signalling events by not only increasing
      the expression of specific PDE4 cAMP phosphodiesterases but also by down
      regulating specific isoforms, such as is shown here for PDE4A10 in cardiac
      myocytes.

PMID- 18721874
TI  - Thermosensitive polymer-conjugated albumin nanospheres as thermal targeting anti
      cancer drug carrier.
AB  - Thermosensitive Poly(N-isopropylacrylamide-co-acrylamide-co-allylamine) (PNIPAM
      AAm-AA)-conjugated albumin nanospheres (PAN) was developed as a new thermal
      targeting anti-cancer drug carrier by conjugating PNIPAM-AAm-AA on the surface of
      albumin nanospheres (AN). AN with diameter below 200nm and narrow size
      distribution was successfully prepared in the first step with desolvation
      technique. PNIPAM-AAm-AA with different molecular weight (M(w)) was synthesized
      in the second step by radical polymerization and conjugated onto the surface of
      AN. Anti-cancer drug adriamycin (ADR) was then entrapped into the AN and PAN
      during the particle preparation. Compared with AN, the release rate of ADR from
      PAN in trypsin solution was slower, and decreased with increasing the conjugation
      amounts (hairy density) or M(w) of PNIPAM-AAm-AA (hairy length). Moreover, the
      release of ADR from PAN above the cloud-point temperature (T(cp)) of PNIPAM-AAm
      AA became faster due to shrinkage of hairy thermosensitive polymer. To testify
      the thermal targetability in vivo, PAN was incubated with HepG2 cells. As
      expected, PAN can target cancer cells above the T(cp) of PNIPAM-AAm-AA, whereas
      it cannot below the T(cp). These results might reflect that PAN may selectively
      accumulate onto solid tumors that are maintained above physiological temperature
      due to local hyperthermia.

PMID- 18721875
TI  - Development of an in situ forming PLGA drug delivery system I. Characterization
      of a non-aqueous protein precipitation.
AB  - The incorporation of the model protein hen egg white lysozyme into liquid in situ
      forming poly(lactide-co-glycolide) (PLGA) implant or microparticle formulations
      was investigated. Ternary solvent blends of dimethyl sulfoxide (DMSO), ethyl
      acetate and water were used to adjust the protein solubility in order to
      facilitate the incorporation of either dispersed or dissolved protein into the
      polymer solution. Lysozyme formed large gel particles when dispersed directly in
      the polymer solution. These formulations had a pronounced initial release. Non
      aqueous precipitation of lysozyme from solutions in DMSO with ethyl acetate led
      to a reversible aggregation without loss in biological activity. Lysozyme could
      be incorporated in a finely dispersed state through an in situ precipitation by
      non-solvent or polymer addition. Non-aqueous precipitation could thus be utilized
      to manufacture biodegradable in situ forming drug delivery systems containing
      homogeneously distributed and bioactive protein.

PMID- 18721877
TI  - Context-dependent regulation of Groucho/TLE-mediated repression.
AB  - Groucho/TLE proteins are global corepressors that are recruited to target
      promoters by different families of DNA-binding repressors. As these corepressors
      are widely expressed, the long-standing view had been that Groucho/TLE-mediated
      repression is regulated solely by the spatial and temporal distribution of
      partner repressors. It has recently emerged, however, that Groucho/TLE repressor
      activity is itself regulated, in a signal induced, context-dependent manner. Here
      we review the essential roles played by Groucho/TLE factors in different cell
      signalling processes that illustrate different modes for regulating Groucho/TLE
      mediated repression: (i) via the expression of partner repressors; (ii) by
      competition with coactivators and (iii) through post-translational modifications
      of Groucho/TLE. We also discuss how the intrinsic properties of repressors can
      result in differential responses to Groucho/TLE regulation.

PMID- 18721876
TI  - Allergy and eosinophil-associated gastrointestinal disorders (EGID).
AB  - Eosinophil-associated gastrointestinal disorders (EGIDs) are characterized by an
      inappropriate accumulation of eosinophils within the gastrointestinal tract. The
      underlying etiology and pathophysiology that lead to the development of EGID are
      far from elucidated. However, there is growing evidence to support the role of
      aeroallergens and food allergens in the pathogenesis of these disorders. Recent
      advances have highlighted the role of Th2-driven cytokines in the development of
      EGID, and clinical studies have verified that children and adults with EGID often
      have positive skin testing to food allergens. The most common form of EGID,
      eosinophilic esophagitis (EE), has garnered intense investigation following an
      increased recognition over the past decade. Recently, there have been several
      important studies providing insight into both the cellular mechanisms governing
      EE and clinical therapies directed toward the treatment of EE. In the article
      herein, we will review the most recent scientific advances influencing our
      understanding of EGID with special emphasis on the role of allergens in the
      pathogenesis of EGID.

PMID- 18721879
TI  - Genome duplication and the origin of the vertebrate skeleton.
AB  - During vertebrate embryonic development, tissue patterning and differentiation
      are regulated by members of multigene families. Evolutionary expansion of these
      families is thought to have played a role in the evolution of anatomical
      complexity, including the origins of new cell and tissue types. A defining
      feature of vertebrates is an endoskeleton, the primary components of which are
      cartilage and bone. The molecular control of skeletal patterning has been the
      subject of intensive investigation for over two decades. More recently,
      comparative studies of organisms at key phylogenetic positions have highlighted
      the importance of gene duplication in the evolutionary diversification of
      connective tissues. Understanding the natural histories of gene families involved
      in skeletogenesis is therefore central to the issue of vertebrate skeletal
      evolution.

PMID- 18721878
TI  - Back and forth between cell fate specification and movement during vertebrate
      gastrulation.
AB  - Animal body plan arises during gastrulation and organogenesis by the coordination
      of inductive events and cell movements. Several signaling pathways, such as BMP,
      FGF, Hedgehog, Nodal, and Wnt have well-recognized instructive roles in cell fate
      specification during vertebrate embryogenesis. Growing evidence indicates that
      BMP, Nodal, and FGF signaling also regulate cell movements, and that they do so
      through mechanisms distinct from those that specify cell fates. Moreover,
      pathways controlling cell movements can also indirectly influence cell fate
      specification by regulating dimensions and relative positions of interacting
      tissues. The current challenge is to delineate the molecular mechanisms via which
      the major signaling pathways regulate cell fate specification and movements, and
      how these two processes are coordinated to ensure normal development.

PMID- 18721880
TI  - Odorant receptor-mediated signaling in the mouse.
AB  - In the mouse olfactory system, there are approximately 1000 types of odorant
      receptors (ORs), which perform multiple functions in olfactory sensory neurons
      (OSNs). In addition to detecting odors, the functional OR protein ensures the
      singular gene choice of the OR by negative-feedback regulation. ORs also direct
      the axonal projection of OSNs both globally and locally by modulating the
      transcriptional levels of axon-guidance and axon-sorting molecules. In these
      latter processes, the second messenger, cAMP, plays differential roles in the
      fasciculation and targeting of axons. In this review, we will discuss how ORs
      differentially regulate intracellular signals for distinct functions.

PMID- 18721881
TI  - Structural details of the glycosyltransferase step of peptidoglycan assembly.
AB  - The importance of peptidoglycan in forming the basis of the bacterial cell wall
      has led to many studies investigating its synthesis. The step of cross-linkage
      via transpeptidation, and its inhibition by penicillins, has been extremely well
      characterized yet knowledge of the preceding glycosyltransfer reaction remained
      elusive until recently. The structures of two glycosyltransferase enzymes,
      catalyzing membrane-based polymerization of the lipid II monomer unit, have
      presented a means of elucidating the molecular details of this highly desirable
      antibiotic target. Evidence acquired before the publication of the structures is
      related here to these new findings, with particular emphasis on the recognition
      of substrates and inhibitors.

PMID- 18721882
TI  - Multiscale methods for macromolecular simulations.
AB  - In this article we review the key modeling tools available for simulating
      biomolecular systems. We consider recent developments and representative
      applications of mixed quantum mechanics/molecular mechanics (QM/MM), elastic
      network models (ENMs), coarse-grained molecular dynamics, and grid-based tools
      for calculating interactions between essentially rigid protein assemblies. We
      consider how the different length scales can be coupled, both in a sequential
      fashion (e.g. a coarse-grained or grid model using parameterization from MD
      simulations), and via concurrent approaches, where the calculations are performed
      together and together control the progression of the simulation. We suggest how
      the concurrent coupling approach familiar in the context of QM/MM calculations
      can be generalized, and describe how this has been done in the CHARMM
      macromolecular simulation package.

PMID- 18721883
TI  - Organophosphates' resistance in the B-biotype of Bemisia tabaci (Hemiptera:
      Aleyrodidae) is associated with a point mutation in an ace1-type
      acetylcholinesterase and overexpression of carboxylesterase.
AB  - Organophosphate (OP) insecticides are inhibitors of the enzyme
      acetylcholinesterase (AChE), which terminates nerve impulses by catalyzing the
      hydrolysis of the neurotransmitter acetylcholine. Previous biochemical studies in
      Bemisia tabaci (Hemiptera: Aleyrodidae) proposed the existence of two molecular
      mechanisms for OPs' resistance: carboxylesterase- (COE) mediated hydrolysis or
      sequestration and decreased sensitivity of AChE. Here, two acetylcholinesterase
      genes, ace1 and ace2, have been fully cloned and sequenced from an OP-resistant
      strain and an OP-susceptible strain of B. tabaci. Comparison of nucleic acid and
      deduced amino acid sequences revealed only silent nucleotide polymorphisms in
      ace2, and one mutation, Phe392Trp (Phe331 in Torpedo californica), in ace1 of the
      resistant strain. The Phe392Trp mutation is located in the acyl pocket of the
      active site gorge and was recently shown to confer OP insensitivity in Culex
      tritaeniorhynchus. In addition, we also report on the isolation of two
      carboxylesterase genes (coe1 and coe2) from B. tabaci, the first
      carboxylesterases to be reported from this species. We show that one of the
      genes, coe1, is overexpressed ( approximately 4-fold) in the OP-resistant strain,
      and determine, by quantitative PCR, that the elevated expression is not related
      to gene amplification but probably to modified transcriptional control. Lastly,
      we bring new biochemical evidence that support the involvement of both AChE
      insensitivity and COE metabolism in resistance to OP insecticides in the
      resistant strain.

PMID- 18721884
TI  - Significant structural but not physiological changes in cortical neurons of 12
      month-old Tg2576 mice.
AB  - Amyloid-beta (Abeta) plays a key role in the etiology of Alzheimer's disease, and
      pyramidal cell dendrites exposed to Abeta exhibit dramatic structural
      alterations, including reduced dendritic spine densities. To determine whether
      such structural alterations lead to electrophysiological changes, whole-cell
      patch clamp recordings with biocytin filling were used to assess both the
      electrophysiological and morphological properties of layer 3 pyramidal cells in
      frontal cortical slices prepared from 12-month-old Tg2576 amyloid precursor
      protein (APP) mutant vs. wild-type (Wt) mice. Tg2576 cells exhibited
      significantly increased dendritic lengths and volumes and decreased spine
      densities, while the total number of spines was not different from Wt. Tg2576 and
      Wt cells did not differ with regard to passive membrane, action potential firing
      or glutamatergic spontaneous excitatory postsynaptic current properties. Thus,
      overexpression of mutated APP in young Tg2576 mice leads to significant changes
      in neuronal morphological properties which do not have readily apparent
      functional consequences.

PMID- 18721886
TI  - Comparison of antiviral efficiency of immune responses in shrimp.
AB  - The antiviral effectiveness of three major immune responses including
      phagocytosis, apoptosis and proPO system in the shrimp Marsupenaeus japonicus was
      characterized. It was found that the suppression of apoptosis and phagocytosis in
      vivo by their corresponding inhibitors resulted in the increase of white spot
      syndrome virus (WSSV) copies and shrimp mortality, whereas the inhibition of
      phenol oxidase generated the least influence on WSSV infection and shrimp
      mortality. These results suggest that apoptosis and phagocytosis were the
      essential immune responses to protect shrimp from virus infection, while the
      phenol-oxidase-dependent proPO system plays a comparatively minor role in
      antiviral defense of shrimp.

PMID- 18721885
TI  - Calpain activity contributes to the control of SNAP-25 levels in neurons.
AB  - Calpains are a family of calcium-dependent proteases with abundant expression in
      the CNS, and potent in cleaving some synaptic components. Assessment of calpain
      activity by its fluorescent substrate, Boc-Leu-Met-CMAC, revealed that cultured
      neurons display a significant level of constitutive enzyme activity. Notably,
      calpain activity differs in distinct neuronal populations, with a significantly
      higher level of activity in GABAergic cells. Using selectively-enriched cultures
      of fast-spiking GABAergic interneurons, we show that calpain activity partially
      contributes to the post-translational down regulation of SNAP-25, a calpain
      substrate, in differentiated GABA cells. In addition, we demonstrate that SNAP-25
      is cleaved by calpain in response to acute seizures induced by intraperitoneal
      kainate injection in vivo. These data indicate that calpains in neurons are
      active even at physiological calcium concentrations and that different levels of
      calpain activation in selected neuron subtypes may contribute to the pattern of
      synaptic protein expression.

PMID- 18721887
TI  - Characterization, tissue expression, and immunohistochemical localization of
      MCL3, a C-type lectin produced by Perkinsus olseni-infected Manila clams
      (Ruditapes philippinarum).
AB  - A novel C-type lectin designated Manila clam lectin 3 (MCL3), with a molecular
      weight of 17.380kDa, was identified among haemocyte expressed sequence tags of
      Perkinsus olseni-infected Manila clams. MCL3 was expressed in Escherichia coli
      M15 cells and purified with a Ni-NTA His-binding resin matrix. MCL3 agglutinated
      rabbit erythrocytes in the presence of Ca(+2). MCL3-induced agglutination was
      partially inhibited by GalNAc, Man, lactose, and raffinose, whereas the
      polysaccharides bovine mucin type II and Candida mannan completely inhibited
      agglutination. MCL3 was expressed in the haemocytes of Manila clams 3 days after
      infection with P. olseni and 1 day after infection with Vibrio tapetis. Based on
      real-time PCR analysis, mRNA transcripts of MCL3 were present in the adductor,
      foot, gill, mantle, palp, and siphon of Perkinsus-infected Manila clams.
      Furthermore, MCL3 was detected in the foot, gill, mantle, gonad, digestive gland,
      gonad connective tissue, intestine, and stomach by immunohistochemical
      localization.

PMID- 18721888
TI  - Estimating the influence of attention on population codes in human visual cortex
      using voxel-based tuning functions.
AB  - In order to form stable perceptual representations, populations of sensory
      neurons must pool their output to overcome physiological noise; selective
      attention is then required to ensure that behaviorally relevant stimuli dominate
      these 'population codes' to gain access to awareness. However, the role that
      attention plays in shaping population response profiles has received little
      direct investigation, in part because most traditional neurophysiological methods
      cannot simultaneously assess changes in activity across large populations of
      sensory neurons. Based on single-unit recording studies, current theories hold
      that attending to a relevant feature sharpens the population response profile and
      improves the signal-to-noise ratio of the resulting perceptual representation.
      Here, we test this hypothesis using fMRI and an analysis approach that is able to
      estimate the influence of feature-based attentional modulations on population
      response profiles. We first derive orientation tuning functions for single voxels
      in human primary visual cortex, and then use these tuning functions to sort
      voxels according to their orientation preference. We then show that selective
      attention systematically biases population response profiles so that behaviorally
      relevant stimuli are represented in the visual system at the expense of
      behaviorally irrelevant stimuli. Collectively, the present results (1) provide a
      new approach for precisely characterizing feature-selective responses in human
      sensory cortices and (2) reveal how behavioral goals can shape population
      response profiles to support the formation of coherent perceptual
      representations.

PMID- 18721889
TI  - Gender differences in voluntary micturition control: an fMRI study.
AB  - In the last decade functional imaging has gained substantial importance for
      identifying cortical and subcortical brain regions being involved in the
      micturition circuit. However, possible gender differences are still a matter of
      debate. In the present study we used functional magnetic resonance imaging (fMRI)
      to determine micturition related brain regions in healthy men and compared them
      with those in women to elucidate gender-related differences. fMRI was performed
      at 3 T in 12 healthy men with urge to void due to a filled bladder. In a non
      voiding model they were instructed to contract or to relax the pelvic floor
      muscles repetitively. As previously reported in women, contraction and relaxation
      of pelvic floor muscles induced strong activations in the brainstem and more
      rostral areas in our group of healthy men. In general, men had stronger
      activations during contraction than women in nearly all identified areas. In
      contrast, results for the relaxation condition were similar. Some of the
      differences between contraction and relaxation, formerly detected in females,
      could be found in our group of males as well. The results suggest that in women
      and men the same cortical and subcortical networks exist for micturition control.
      Especially, the well located activations in the putative pontine micturition
      centre and the periaqueductal grey could be identified in both sexes. However,
      pelvic floor muscle control seems to induce different activation intensities in
      men and women.

PMID- 18721890
TI  - Symbolic action priming relies on intact neural transmission along the retino
      geniculo-striate pathway.
AB  - Recent psychophysics studies suggest that the behavioral impact of a visual
      stimulus and its conscious visual recognition underlie two functionally
      dissociated neuronal processes. Previous TMS studies have demonstrated that
      certain features of a visual stimulus can still be processed despite TMS-induced
      disruption of perception. Here, we tested whether symbolic action priming also
      remains intact despite TMS-induced masking of the prime. We applied single-pulse
      TMS over primary visual cortex at various temporal intervals from 20 ms to 120 ms
      during a supraliminal action priming paradigm. This TMS protocol enabled us to
      identify at what exact time point a TMS-induced activity disruption of primary
      visual cortex interferes with conscious visual perception of the prime versus
      (un)conscious behavioral priming of the visual target stimulus. We also
      introduced spatial uncertainty by presenting visual stimuli either above or below
      the fixation cross, while the TMS pulse was always targeting the prime presented
      below fixation. We revealed that TMS over primary visual cortex interferes with
      both conscious visual perception and symbolic behavioral priming in a temporarily
      and spatially specific manner, i.e., only when disrupting primary visual cortex
      at approximately the same temporal stage between 60 and 100 ms after prime onset,
      and only for those prime stimuli presented below fixation. These findings are in
      disagreement with the idea of subliminal action priming being mediated by neural
      pathways bypassing striate cortex, and rather suggest that symbolic action
      priming relies on an intact neural transmission along the retino-geniculo-striate
      pathway. The implications of our findings for previous reports of residual visual
      processing during striate TMS are discussed.

PMID- 18721891
TI  - The JAK kinases: not just another kinase drug discovery target.
AB  - There are four members of the JAK family of protein tyrosine kinases (PTKs) in
      the human genome. Since their discovery in 1989, great strides have been made in
      the understanding of their role in normal intracellular signalling. Importantly,
      their roles in pathologies ranging from cancer to immune deficiencies have placed
      them front and centre as potential drug targets. The recent discovery of the role
      of activating mutations in the kinase-like domain (KLD) of JAK2 in the
      development of polycythemia rubra vera, and the elaboration of KLD mutation as a
      broader mechanism by which cells might become hyperproliferative has sparked
      enormous interest in the development of JAK selective drug candidates. I review
      herein the progress that has been made in the discovery of JAK-targeted
      inhibitors, and discuss the challenges that face the development of these drugs
      for use in the clinic.

PMID- 18721892
TI  - Perceptions of Latin American scientists about science and post-graduate
      education: Introduction to the 5th issue of CBP-Latin America.
AB  - Although science and engineering (S&E) publications and doctoral degree awards in
      Latin America had experienced an impressive growth in the past decades, a
      qualitative evaluation of this increased output must be performed. Previous
      studies have indicated that growth in visibility of Latin American science -
      determined by ratio of citations per paper - has not kept pace with the increase
      in number of publications. In the present editorial, we analyzed - by means of a
      12-item questionnaire - the individual perceptions of forty senior researchers
      involved in CBP-Latin America (29 Brazilians and 11 non-Brazilians) plus a
      special group composed by six extraordinary Latin American scientists (the
      "masters"). The questionnaire - using 6-point Likert-like scale for
      quantification of perception - focused on issues surrounding doctoral educational
      system as well as the governmental educational policies and publication pressure
      from funding agencies. In general, the most striking result was the perception
      (by 82% of respondents) of lack of job opportunities for people holding a PhD
      diploma in the field of comparative biochemistry and physiology. Other major
      trends include (i) lack of satisfaction with governmental policies for science
      and post-graduate education due to policies promoting mass production for papers
      and PhD diplomas (65-77% of respondents felt that way) (ii) that current PhD
      students are doing an adequate job, but have not improved in quality as compared
      to those from 10 years ago (the same was observed for PhD thesis in terms of
      present versus past), and (iii) that research infrastructure and the curricula of
      post-graduate courses do not constitute a problem, but (iv) recent-PhDs are not
      as fit as they should be in paper-writing skills, especially as perceived by
      Brazilian respondents. The general perceptions were very similar among
      Brazilians, non-Brazilians and "masters". The use of a larger study-population,
      with scientists of more diverse fields is the next logical step to best evaluate
      the level of satisfaction about science and post-graduate policies in the
      continent. Finally, this fifth and last special issue of CBP-Latin America
      celebrates the contribution of 20 new manuscripts, which adds up to 118 published
      studies highlighting the depth, breadth and enthusiasm of Latin American
      comparative biochemistry and physiology - enjoy.

PMID- 18721893
TI  - Seasonal variation in thermal energetics of the Australian owlet-nightjar
      (Aegotheles cristatus).
AB  - Many birds living in regions with seasonal fluctuations in ambient temperatures
      (T(a)) typically respond to cold by increasing insulation and adjusting metabolic
      rate. Seasonal variation in thermal physiology has not been studied for the
      Caprimulgiformes, an order of birds that generally have basal metabolic rates
      (BMR) lower than predicted for their body mass. We measured the metabolic rate
      and thermal conductance of Australian owlet-nightjars (Aegotheles cristatus)
      during summer and winter using open-flow respirometry. Within the thermoneutral
      zone (TNZ; 31.3 to 34.8 degrees C), there was no seasonal difference in BMR or
      thermal conductance (C), but body temperature was higher in summer- (38.2+/-0.3
      degrees C) than winter-acclimatized (37.1+/-0.5 degrees C) birds. Below the TNZ,
      resting metabolic rate (RMR) increased linearly with decreasing T(a), and RMR and
      C were higher for summer- than winter-acclimatized birds. The mean mass-specific
      BMR of owlet-nightjars (1.27 mL O(2) g(-1) h(-1)) was close to the allometrically
      predicted value for a 45 g Caprimulgiformes, but well below that predicted for
      birds overall. These results suggest that owlet-nightjars increase plumage
      insulation to cope with low winter T(a), which is reflected in the seasonal
      difference in RMR and C below the TNZ, rather than adjusting BMR.

PMID- 18721894
TI  - Embryo lipoproteins and yolk lipovitellin consumption during embryogenesis in
      Macrobrachium borellii (Crustacea: Palaemonidae).
AB  - The prawn Macrobrachium borellii has lecithotrophic eggs with highly-abbreviated
      development. The major yolk component is lipovitellin (LV), a lipoprotein with
      30% lipids (by weight). LV consumption during embryogenesis was followed by ELISA
      and Western blot analysis using an anti-LV polyclonal antibody. No cross-reacting
      proteins were observed and LV-like lipoproteins were strongly recognized by the
      antibody in hemolymph (vitellogenin), yolk (LV) and embryos (LVe), as determined
      by Western Blot analysis. LV decreased significantly along development from 9.4
      to 1.1 microg/mg egg. Consumption rate of LV was slow in early embryogenesis,
      followed by a rapid utilization in late embryonic stages. Significant LVe amounts
      were still present at hatching. LV apolipoproteins were selectively degraded
      during embryo development, being the highest molecular weight subunit the most
      affected. Comparison among in vitro, in vivo and theoretical proteolysis
      suggested that trypsin may be involved in LV degradation during late
      embryogenesis. Embryo lipoprotein (HDLe) synthesis was first detected at stage 6.
      HDLe shared the same density, MW and subunit composition as adult hemolymph
      HDL(1) and did not cross-react with LV-like lipoproteins. Though expressed at low
      concentration, it fulfilled embryo needs for lipid transport among organs.

PMID- 18721895
TI  - Challenges for drug studies in children: CYP3A phenotyping as example.
AB  - A paucity of data exists on the disposition and effect of drugs in young
      children. This information gap can be reduced by elucidating developmental
      principles of absorption, distribution, metabolism and excretion (ADME) in vivo.
      Such knowledge might enable the prediction of the disposition of individual drugs
      in children over the whole pediatric age range. CYP3A, the most abundant human
      drug metabolizing enzyme, is involved in the metabolism of more than 50% of all
      marketed drugs. Hence, elucidating the developmental pattern of CYP3A in relation
      to genetic background, disease and comedications might greatly enhance our
      knowledge on drug disposition in children. Several methods have been used to
      determine in vivo CYP3A activity in human adults, while similar studies in
      children face several ethical, practical and scientific challenges. The aim of
      this review is to identify these challenges and offer feasible solutions for
      studying drugs in young children, with an emphasis on CYP3A phenotyping as an
      example.

PMID- 18721896
TI  - Principles for 3D/4D QSAR classification of drugs.
AB  - The principles for the 3D/4D classification of drugs are introduced in this
      article. Based on these principles, new techniques for the reconstruction of
      complementary selfconsistent receptor fields for the classification of drugs,
      taking into account their multitautomeric and multiconformational states, are
      created. The series of examples of classification of drugs by their activity
      (active or nonactive), by their mechanisms of action, by their target and binding
      site and by the most important stages of their action are given. Prospects for
      rational drug design are highlighted.

PMID- 18721897
TI  - Mutagenicity of native cigarette mainstream smoke and its gas/vapour phase by use
      of different tester strains and cigarettes in a modified Ames assay.
AB  - The "Bacterial Reverse Mutation Assay" is generally accepted to analyse the
      genotoxic capacity of single compounds or complex mixtures such as cigarette
      smoke condensates. With an adapted and modified Ames assay, the mutagenicity of
      native cigarette mainstream whole smoke (WS) and its gas/vapour phase (GVP) was
      studied. The bacteria were directly exposed to the smoke in a CULTEX1 system
      closely connected to a smoking robot (VC10). A variety of standard tester strains
      (TA98, TA100, TA1535, TA1537, TA1538, TA102, WP2uvrApKM101) and descendants of
      TA98 (YG1021, YG1024, YG1041) and TA100 (YG1026, YG1029 and YG1042) were exposed
      to whole and filtered smoke of the research cigarette K2R4F to find the most
      sensitive strains for analysing the mutagenic activity of these test atmospheres.
      Mutagenicity of WS was detected by TA98, TA100 and their YG descendant strains as
      well as by WP2uvrApKM101 in the presence of S9 mix. The GVP induced a mutagenic
      signal in TA100, YG1029 and YG1042 and WP2uvrApKM101 only in the absence of S9
      mix. To detect mutagenicity in WS the presence of the plasmid pKM101 is required
      and a frame-shift mutation is more effective than a missense mutation. To detect
      mutagenicity in GVP, the presence of the plasmid pKM101 and a missense mutation
      are required. The differentiating capacity of this modified Ames assay was
      demonstrated by exposing strain TA98 to WS and TA100 to the GVP of cigarettes
      with different tar content. The mutagenic activity of WS and the GVP increased
      with rising tar content of the cigarettes with two exceptions in WS. Thus, the
      concept of tar content alone is misleading and does not reflect the mutagenic
      activity of a cigarette.

PMID- 18721898
TI  - Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises.
AB  - The strategy of 'drugging the cancer kinome' has led to the successful
      development and regulatory approval of several novel molecular targeted agents.
      The spotlight is now shifting to the phosphatidylinositide 3-kinase (PI3K)-AKT
      mammalian target of rapamycin (mTOR) pathway as a key potential target. This
      review details the role of the pathway in oncogenesis and the rationale for
      inhibiting its vital components. The focus will be on the progress made in the
      development of novel therapies for cancer treatment, with emphasis placed on
      agents that have entered clinical development. Strategies involving horizontal
      and vertical blockade of the pathway, as well as the use of biomarkers to select
      appropriate patients and to provide proof of target modulation will also be
      highlighted. Finally, we discuss the issues and limitations involved with
      targeting the PI3K-AKT-mTOR pathway, and predict what the future may hold for
      these novel anticancer therapeutics.

PMID- 18721899
TI  - n-3 fatty acids (fish oil) for epilepsy, cardiac risk factors, and risk of SUDEP:
      clues from a pilot, double-blind, exploratory study.
AB  - OBJECTIVE: The goal of the work described here was to determine the effect of
      high-dose n-3 fatty acids (eicosapentanoic acid+docosahexanoic acid, fish oil) on
      several outcomes in subjects with refractory epilepsy, including seizure
      severity, seizure frequency, cardiac risk factors, and heart rate variability, in
      a pilot, exploratory planning trial. METHODS: Pilot, randomized, double-blind two
      period crossover clinical trial of high-dose fish oil (9600 mg of fish oil/day,
      2880 mg of n-3 fatty acids) in 11 subjects with refractory seizures. Outcomes
      included seizure frequency, seizure severity, lipid panel, and heart rate
      variability as measured by SDNN and SDANN (defined as the standard deviation of
      all normal R-R intervals for 1h, and the standard deviation of all R-R intervals
      in each successive 5-min epoch, respectively). RESULTS: Preliminary data
      identified trends towards lower seizure severity, lower triglycerides, higher
      HDL, and increased SDNN/SDANN in those with low SDNN/SDANN at baseline
      (Spearman's correlation=-0.65, P=0.03). No positive effect on seizure frequency
      was identified. CONCLUSIONS: Further study of the effect of n-3 fatty acids is
      indicated in people with epilepsy, as favorable trends were identified on cardiac
      risk factors (triglycerides) and in a subgroup with low heart rate variability
      (low SDNN/SDANN), a marker of sudden death risk. To our knowledge, this is the
      first trial to explore the beneficial effects of n-3 fatty acids on cardiac risk
      factors and heart rate variability in people with epilepsy.

PMID- 18721900
TI  - Vaidurya: a multiple-ontology, concept-based, context-sensitive clinical
      guideline search engine.
AB  - We designed and implemented a generic search engine (Vaidurya), as part of our
      Digital clinical-Guideline Library (DeGeL) framework. Two search methods were
      implemented in addition to full-text search: (1) concept-based search, which
      relies on pre-indexing the guidelines in a clinically meaningful fashion, and (2)
      context-sensitive search, which relies on first semi-structuring the guidelines
      according to a given ontology, then searching for terms within specific labeled
      text segments. The Vaidurya engine is fully functional and is used within the
      DeGeL system. We describe the Vaidurya ontological and algorithmic framework; we
      also briefly summarize the results of a detailed evaluation in the clinical
      guideline domain, demonstrating that both concept-based and context-sensitive
      ontology-independent search are highly feasible and significantly improve on free
      text search retrieval performance. We conclude by analyzing the limitations and
      advantages of the approach, and the steps that we have started to take to extend
      it based on user feedback.

PMID- 18721901
TI  - Recruitment of minority and underserved populations in the United States: the
      Centers for Population Health and Health Disparities experience.
AB  - OBJECTIVE: The recruitment of minority and underserved individuals to research
      studies is often problematic. The purpose of this study was to describe the
      recruitment experiences of projects that actively recruited minority and
      underserved populations as part of The Centers for Population Health and Health
      Disparities (CPHHD) initiative. METHODS: Principal investigators and research
      staff from 17 research projects at eight institutions across the United States
      were surveyed about their recruitment experiences. Investigators reported the
      study purpose and design, recruitment methods employed, recruitment progress,
      problems or challenges to recruitment, strategies used to address these problems,
      and difficulties resulting from Institutional Review Board (IRB) or Health
      Insurance Portability and Accountability Act of 1996 (HIPAA) requirements.
      Additionally, information was collected about participant burden and
      compensation. Burden was classified on a three-level scale. Recruitment results
      were reported as of March 31, 2007. RESULTS: Recruitment attainment ranged from
      52% to 184% of the participant recruitment goals. Commonly reported recruitment
      problems included administrative issues, and difficulties with establishing
      community partnerships and contacting potential participants. Long study
      questionnaires, extended follow-up, and narrow eligibility criteria were also
      problematic. The majority of projects reported difficulties with IRB approvals,
      though few reported issues related to HIPAA requirements. Attempted solutions to
      recruitment problems varied across Centers and included using multiple
      recruitment sites and sources and culturally appropriate invitations to
      participate. Participant burden and compensation varied widely across the
      projects, however, accrual appeared to be inversely associated with the amount of
      participant burden for each project. CONCLUSION: Recruitment of minority and
      underserved populations to clinical trials is necessary to increase study
      generalizbility and reduce health disparities. Our results demonstrate the
      importance of flexible study designs which allow adaptation to recruitment
      challenges. These experiences also highlight the importance of involving
      community members and reducing participant burden to achieve success in
      recruiting individuals from minority and underserved populations.

PMID- 18721902
TI  - Strategies to enhance patient recruitment and retention in research involving
      patients with a first episode of mental illness.
AB  - Recruitment and retention of research participants is often the most labor
      intensive and difficult component of clinical trials. Poor recruitment and
      retention frequently pose as a major barrier in the successful completion of
      clinical trials. In fact, many studies are prematurely terminated, or their
      findings questioned due to low recruitment and retention rates. The conduct of
      clinical trials involving youth with a first episode of mental illness comes with
      additional challenges in recruitment and retention including barriers associated
      with engagement and family involvement. To develop effective early interventions
      for first episode mental illness, it is necessary to develop strategies to
      enhance recruitment and retention in this patient population. This article
      presents the recruitment and retention challenges experienced in two clinical
      trials: one involving participants experiencing a first episode of depression and
      one involving participants experiencing a first episode psychosis. Challenges
      with recruitment and retention are identified and reviewed at both the patient
      level and clinician level. Strategies that were implemented to enhance
      recruitment and retention in these two studies are also discussed. Finally,
      ethical issues to consider when implementing these strategies are also
      highlighted.

PMID- 18721903
TI  - Immunopotentiation of Caffeoyl Glycoside from Picrorhiza scrophulariiflora on
      activation and cytokines secretion of immunocyte in vitro.
AB  - Many natural products have been used as immunomodulators either as
      immunosuppressants or immunostimulators. Recently, our lab has successfully
      isolated a 1,6-di-O-caffeoyl-beta-D-glucopyranoside, monomer named Caffeoyl
      Glycoside (CG) from the roots of Picrorhiza scrophulariiflora (Kutki). In the
      present study, we evaluated the effects of this compound on immunomodulation in
      vitro. Our results showed that CG stimulated cell proliferation of splenocytes
      and peritoneal macrophages, and enhanced the cytotoxicity of natural killer (NK)
      cells significantly. CG also increased CD4 and CD8 cell populations. Moreover, we
      found that CG has immunomodulatory activity by regulating expression of Th1 and
      Th2 related cytokines. Taken together, these results indicated that CG might have
      potential effects in regulating the immune system, and this compound might be a
      useful immunotherapeutic agent in treating various immunity-related diseases.

PMID- 18721904
TI  - Oral administration of allergen extracts from Dermatophagoides farinae
      desensitizes specific allergen-induced inflammation and airway
      hyperresponsiveness in rats.
AB  - Clinically sublingual immunotherapy (SLIT) by using allergen extracts effectively
      alleviates the symptoms of allergic rhinitis and asthma. Supposed that oral
      administration of high-dose of allergen extracts imitates SLIT and may prevent
      IgE-related responses in allergic diseases, we investigated the effects of oral
      administration of allergen extracts from Dermatophagoides farinae (Derf) on
      allergen-induced inflammation and airway hyperresponsiveness (AHR) in a model of
      asthmatic rat. After administration to the specific Derf-sensitized rats with
      Derfdrop solution containing Derf1 and Derf2 extracts derived from Derf, the
      effects of Derfdrop on AHR, inflammatory cell accumulation, cytokine production
      in the bronchoalveolar lavage fluid and lung tissue, as well as serum IgE and IgG
      levels were investigated. Results indicated that Derfdrop not only dose
      dependently prevented the AHR in response to methacholine, but also significantly
      reduced the serum total and allergen-specific IgE levels, all the maximal effects
      were achieved at dose of 5 mg/kg/d, and were as comparable as those of
      dexamethasone at dose of 1.0 mg/kg/d. Furthermore, oral administration of
      Derfdrop not only dose-dependently elevated allergen-specific serum IgG levels
      and reduced total and allergen-specific IgE levels, but also normalized the
      imbalance between the Th1 cytokine, IFN-gamma and Th2 cytokine, IL-4. Finally,
      oral administration of Derfdrop significantly reduced Goblet cell hyperplasia and
      eosinophilia in the Derf-sensitized allergic rat model. These data suggest that
      Derfdrop effectively improves specific allergen-induced inflammation and AHR in
      Derf-sensitized and -challenged rats and provide with the rationale for clinical
      SLIT by using Derfdrop in a specific allergen-induced asthma.

PMID- 18721906
TI  - The rate of base excision repair of uracil is controlled by the initiating
      glycosylase.
AB  - Uracil in DNA is repaired by base excision repair (BER) initiated by a DNA
      glycosylase, followed by strand incision, trimming of ends, gap filling and
      ligation. Uracil in DNA comes in two distinct forms; U:A pairs, typically
      resulting from replication errors, and mutagenic U:G mismatches, arising from
      cytosine deamination. To identify proteins critical to the rate of repair of
      these lesions, we quantified overall repair of U:A pairs, U:G mismatches and
      repair intermediates (abasic sites and nicked abasic sites) in vitro. For this
      purpose we used circular DNA substrates and nuclear extracts of eight human cell
      lines with wide variation in the content of BER proteins. We identified the
      initiating uracil-DNA glycosylase UNG2 as the major overall rate-limiting factor.
      UNG2 is apparently the sole glycosylase initiating BER of U:A pairs and generally
      initiated repair of almost 90% of the U:G mismatches. Surprisingly, TDG
      contributed at least as much as single-strand selective monofunctional uracil-DNA
      glycosylase 1 (SMUG1) to BER of U:G mismatches. Furthermore, in a cell line that
      expressed unusually high amounts of TDG, this glycosylase contributed to
      initiation of as much as approximately 30% of U:G repair. Repair of U:G
      mismatches was generally faster than that of U:A pairs, which agrees with the
      known substrate preference of UNG-type glycosylases. Unexpectedly, repair of
      abasic sites opposite G was also generally faster than when opposite A, and this
      could not be explained by the properties of the purified APE1 protein. It may
      rather reflect differences in substrate recognition or repair by different
      complex(es). Lig III is apparently a minor rate-regulator for U:G repair. APE1,
      Pol beta, Pol delta, PCNA, XRCC1 and Lig I did not seem to be rate-limiting for
      overall repair of any of the substrates. These results identify damaged base
      removal as the major rate-limiting step in BER of uracil in human cells.

PMID- 18721905
TI  - Selection by drug resistance proteins located in the mitochondria of mammalian
      cells.
AB  - Transformation of mitochondria in mammalian cells is now a technical challenge.
      In this report, we demonstrate that the standard drug resistant genes encoding
      neomycin and hygromycin phosphotransferases can potentially be used as selectable
      markers for mammalian mitochondrial transformation. We re-engineered the drug
      resistance genes to express proteins targeted to the mitochondrial matrix and
      confirmed the location of the proteins in the cells by fusing them with GFP and
      by Western blot and mitochondrial content mixing analyses. We found that the
      mitochondrially targeted-drug resistance proteins confer resistance to high
      levels of G418 and hygromycin without affecting the viability of cells.

PMID- 18721907
TI  - "SAPHO syndrome and infections".
AB  - The syndrome of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO)
      encompasses a broad spectrum of cutaneous manifestations associated with osteitic
      and hyperostotic lesions, which typically may involve the anterior chest wall
      (ACW). The aetiopathogenetic mechanisms as well as the nosographic framing of the
      disease are still not fully defined although an important role has been suggested
      for Propionibacterium acnes (P. acnes). This germ might be able to stimulate both
      the innate and the T-cell-mediated immune system. The elicited immunological
      response could be an attempt to eliminate the germ thus inducing the perpetuation
      of the inflammation. Whether the osteo-articular changes seen in SAPHO could be
      attributable directly to the infection or to an inflammatory reaction induced by
      pathogenic material remains a debated issue. The current concept of SAPHO
      syndrome as a reactive infectious osteitis in genetic predisposed subjects seems
      appealing, but it has not been yet demonstrated.

PMID- 18721908
TI  - Altered T and B lymphocyte signaling pathways in lupus.
AB  - Systemic lupus erythematosus (SLE) has long been recognized to be characterized
      by dysregulated signaling pathways in T and B lymphocytes, beginning with
      observations of cellular hyperactivity and hyperresponsiveness, and evolving to
      recent studies focused upon the genetic and molecular bases of such phenomena.
      This review focuses on recently elucidated signaling abnormalities currently
      thought to be intrinsic to T and/or B cells in human SLE.

PMID- 18721909
TI  - MIF in autoimmunity and novel therapeutic approaches.
AB  - Macrophage migration inhibitory factor (MIF) is a multipotent cytokine implicated
      in the pathogenesis of numerous inflammatory and autoimmune disorders. Since anti
      cytokine therapy is considered to be a promising therapeutic strategy, selective
      targeting of MIF with either anti-MIF antibody or specific chemical MIF
      inhibitors might offer new therapeutic avenues for these disorders. Considering
      the unique relationship between MIF and glucocorticoids, therapeutic antagonism
      of MIF could also represent an effective approach for steroid-sparing therapies
      in patients with refractory autoimmune diseases.

PMID- 18721910
TI  - Overview: the neurochemistry of respiratory control.
AB  - This special issue of Respiratory Physiology and Neurobiology surveys a broad
      range of topics focused on the neurochemical control of breathing. A variety of
      approaches have integrated the neurochemistry of breathing with the physiology of
      individual neurons, with the neuroanatomy of brainstem and forebrain respiratory
      circuits, and with the clinical pathology of respiratory disorders all of which
      has been fueled by the ongoing explosion of information in the molecular biology
      of the nervous system. Accordingly, substantial progress has identified
      neurotransmitters, neuromodulators, receptors, signaling cascades, trophic
      factors, hormones, and genes mediating normal and pathological breathing. Dynamic
      changes in the neurochemistry of breathing are addressed with respect to
      brainstem development, environmental challenges such as intermittent or chronic
      hypoxia, and as a function of the sleep-wake cycle. Respiratory disruption has
      also been identified in an increasing variety of genetic-based disorders and
      remarkable progress has been made in determining the affected genes and their
      mutations that negatively impact respiration.

PMID- 18721911
TI  - Post-exercise diaphragm shielding: a novel approach to exercise-induced
      diaphragmatic fatigue.
AB  - Based on the "post-exercise diaphragm shielding" hypothesis this study tested
      whether both diaphragmatic force-generation (DFG) and diaphragmatic fatigue (DF)
      remain unchanged during consecutive exercise-trials. Twelve subjects (V(O2 max)
      58.4+/-6.6 ml kg(-1) min(-1)) performed three consecutive exercise-trials
      (T(alpha)/T(beta)/T(gamma); workload(max) 85% V(O2 max)) each followed by
      recovery (6 min). Twitch transdiaphragmatic pressure during supramaximal magnetic
      phrenic nerve stimulation (TwPdi, every 30s), ratings of perceived exertion (RPE,
      every 90 s) and ergospirometric data (continuously) were assessed throughout the
      entire protocol (46.5 min). DFG and DF did not differ among all trials (TwPdi
      baseline: 2.2+/-0.7 kPa; TwPdi-peak: T(alpha)/T(beta)/T(gamma) 3.1+/-0.7 kPa vs
      3.0+/-0.8 kPa vs 3.2+/-0.8 kPa; TwPdi-bottom: T(alpha)/T(beta)/T(gamma) 1.9+/-0.6
      kPa vs 2.0+/-0.7 kPa vs 1.8+/-0.5 kPa, both p>0.4, RM-ANOVA). Furthermore, TwPdi
      revealed close relationships with RPE (r=0.91, p<0.0001) and oxygen uptake
      (r=0.94, p<0.0001) during exercise. In conclusion, both DFG (baseline-to-peak)
      and DF (baseline-to-bottom) achieve similar magnitudes during and after
      consecutive exercise-trials and are closely linked to RPE and oxygen uptake. This
      suggests that DF neither reflects impaired diaphragmatic function nor impairs
      exercise performance; rather it is likely to reflect post-exercise diaphragm
      shielding.

PMID- 18721912
TI  - Lung and chest wall mechanics during exercise: effects of expiratory flow
      limitation.
AB  - This short review summarizes how lung and chest wall mechanics can be modelled
      and which are the mechanical constraints imposed on the ventilatory system and
      its components during exercise. In healthy humans the structural and functional
      characteristics of the ventilator pump are able to meet the increased demands of
      ventilation during exercise and it is rare that arterial blood gas is
      significantly altered up to maximal exercise. In contrast, exercise is frequently
      limited by the ventilator system in disease, especially when altered mechanical
      properties of the airway and lung make expiratory flow limitation (EFL) a common
      feature. EFL is a phenomenon that can be understood in terms of the viscous
      effects of gas flowing from the alveoli to the airway opening along a collapsible
      airway which leads during exercise to dynamic hyperflation and several
      abnormalities of the ventilatory pump. These, in turn, determine a series of
      secondary manifestations, namely dyspnoea, exercise limitation and hypercapnia
      that can cause serious morbidity.

PMID- 18721913
TI  - Left-ventricular non-compaction (LVNC): a clinical feature more often observed in
      terminal deletion 1p36 than previously expected.
AB  - Deletion of 1p36 (OMIM 607872) is estimated to be the most common distal terminal
      deletion syndrome. We describe a previously unreported, typically affected two
      month-old girl with this microdeletion syndrome, who additionally suffers from
      left-ventricular non-compaction (LVNC). Recently, this congenital heart defect,
      characterized by prominent left-ventricular trabeculae and deep intertrabecular
      recesses, was reported in 12 further patients (excluding those reported only in
      abstract form) with terminal deletion of 1p36, leading to the conclusion that
      this cardiomyopathy is common in patients with this chromosomal aberration. We
      hypothesize that a gene in 1p36 might be responsible for LVNC.

PMID- 18721914
TI  - Do masticatory functional changes influence the mandibular morphology in adult
      rats.
AB  - OBJECTIVE: This study aimed to investigate the effect of masticatory functional
      changes on the lateral view morphology of the mandible in adult rats. DESIGN:
      Sixty 21-day-old male Sprague-Dawley rats were divided into two groups. Sixteen
      received ordinary (hard) food during the whole experimental period (normal
      group). The remaining 44 received a soft diet during 21 weeks to develop a
      hypofunctional masticatory system. Then, the now adult animals were divided into
      two equal groups: one continued on a soft diet (hypofunctional group), and the
      other changed to an ordinary diet with the aim of functionally rehabilitating
      their masticatory system (rehabilitation group). After another 6 weeks all
      animals were sacrificed and their left mandible was dissected, photographed and
      customised cephalometric software was used to perform morphometric measurements.
      RESULTS: The area of the mandible was smaller in the hypofunctional compared to
      the normal group. Interestingly, the alveolar process was shorter in the normal
      group. Morphometric analysis revealed significant differences such as the area of
      the angular process and the inclination of the condylar process. The
      rehabilitation group was only marginally different compared to the hypofunctional
      group, although a general tendency to approach (catch-up) the normal group was
      observed, and one morphometric variable (condylar base inclination) was indeed
      significantly different. CONCLUSIONS: Morphometric analysis revealed only
      marginal changes of the adult rat mandibular morphology during a 6-week period of
      masticatory function rehabilitation. However, the observed catch-up tendency
      might suggest that a longer rehabilitation period may have significant effect on
      mandibular morphology.

PMID- 18721916
TI  - Individual differences in the perception of similarity and difference.
AB  - Thematically related concepts like coffee and milk are judged to be more similar
      than thematically unrelated concepts like coffee and lemonade. We investigated
      whether thematic relations exert a small effect that occurs consistently across
      participants (i.e., a generalized model), or a large effect that occurs
      inconsistently across participants (i.e., an individualized model). We also
      examined whether difference judgments mirrored similarity or whether these
      judgments were, in fact, non-inverse. Five studies demonstrated the necessity of
      an individualized model for both perceived similarity and difference, and
      additionally provided evidence that thematic relations affect similarity more
      than difference. Results suggest that models of similarity and difference must be
      attuned to large and consistent individual variability in the weighting of
      thematic relations.

PMID- 18721915
TI  - Isolation and characterization of an immortalized oral keratinocyte cell line of
      mouse origin.
AB  - OBJECTIVE: To establish an oral epithelial cell line of mouse origin for
      molecular and biochemical assays. DESIGN: Epithelial cells were isolated from the
      oral cavity of adult mice and established as a spontaneously immortalized cell
      line in culture, designated immortalized oral keratinocyte cells (IMOK cells).
      The cells were then characterized for growth characteristics, differentiation
      potential, karyotype, transfectability, susceptibility to viral infection and
      responses to siRNA. RESULTS: The IMOK cells exhibit robust growth in both serum
      containing and serum-free medium for at least 100 population doublings. IMOK
      cells have a near diploid karyotype, express keratinocyte marker proteins and can
      be induced to undergo differentiation by the addition of high levels of calcium
      to the medium. The differentiation process is characterized by morphological
      changes and by the induction of oral epithelium specific differentiation marker
      proteins such as K4 and K13. Transient transfection analyses reveal that IMOK
      cells are highly transfectable and that several promoters of epithelial cells are
      active in these cells. Moreover, upon differentiation with calcium, there is an
      up-regulation of differentiation-specific K4 and Elf5 promoter activity. Finally,
      we show that the oral keratinocytes are also amenable to infection with
      retroviruses and to siRNA-based knockdown of gene expression. CONCLUSIONS: Our
      study is the first to establish an immortalized oral keratinocyte cell line of
      murine origin that can recapitulate the oral epithelium differentiation program
      and thus could serve as a useful tool for toxicological and molecular analyses of
      the oral tissue.

PMID- 18721917
TI  - Friend or foe: the effect of implicit trustworthiness judgments in social
      decision-making.
AB  - The human face appears to play a key role in signaling social intentions and
      usually people form reliable and strong impressions on the basis of someone's
      facial appearance. Therefore, facial signals could have a substantial influence
      on how people evaluate and behave towards another person in a social interaction,
      such as an interactive risky decision-making game. Indeed, there is a growing
      body of evidence that demonstrates that social behavior plays a crucial role in
      human decision-making. Although previous research has demonstrated that explicit
      social information about one's partner can influence decision-making behavior,
      such as knowledge about the partner's moral status, much less is known about how
      implicit facial social cues affect strategic decision-making. One particular
      social cue that may be especially important in assessing how to interact with a
      partner is facial trustworthiness, a rapid, implicit assessment of the likelihood
      that the partner will reciprocate a generous gesture. In this experiment, we
      tested the hypothesis that implicit processing of trustworthiness is related to
      the degree to which participants cooperate with previously unknown partners.
      Participants played a Trust Game with 79 hypothetical partners who were
      previously rated on subjective trustworthiness. In each game, participants made a
      decision about how much to trust their partner, as measured by how much money
      they invested with that partner, with no guarantee of return. As predicted,
      people invested more money in partners who were subjectively rated as more
      trustworthy, despite no objective relationship between these factors. Moreover,
      the relationship between the amount of money offered seemed to be stronger for
      trustworthy faces as compared to untrustworthy faces. Overall, these data
      indicate that the perceived trustworthiness is a strong and important social cue
      that influences decision-making.

PMID- 18721918
TI  - Twelve-month-olds communicate helpfully and appropriately for knowledgeable and
      ignorant partners.
AB  - In the current study we investigated whether 12-month-old infants gesture
      appropriately for knowledgeable versus ignorant partners, in order to provide
      them with needed information. In two experiments we found that in response to a
      searching adult, 12-month-olds pointed more often to an object whose location the
      adult did not know and thus needed information to find (she had not seen it fall
      down just previously) than to an object whose location she knew and thus did not
      need information to find (she had watched it fall down just previously). These
      results demonstrate that, in contrast to classic views of infant communication,
      infants' early pointing at 12 months is already premised on an understanding of
      others' knowledge and ignorance, along with a prosocial motive to help others by
      providing needed information.

PMID- 18721919
TI  - Oxidative stress in mouse plasma and lungs induced by cigarette smoke and
      lipopolysaccharide.
AB  - Short-term exposure to cigarette smoke (CS) or lipopolysaccharide (LPS) leads to
      acute lung inflammation through oxidant-antioxidant imbalance. We studied the
      response in mice exposed to smoke or LPS during five consecutive days, as
      measured by superoxide dismutase (SOD), catalase (CAT), and glutathione
      peroxidase (GPx) activities, as well as lipid peroxidation and nitric oxide
      levels in bronchoalveolar lavage fluid (BALF), lung homogenates, and plasma.
      Control mice were exposed to ambient air. Exposure to CS or LPS led to a similar
      influx of alveolar macrophages and neutrophils into the BALF; however,
      hydroxyproline levels were increased only in the CS group (p<0.001); SOD activity
      was increased in the BALF (p<0.001) and lung homogenates (p<0.05) of the CS group
      but was decreased in the BALF (p<0.05), lung homogenates (p<0.05) and plasma
      (p<0.01) of the LPS group. CAT activity was increased in the BALF (p<0.01), lung
      homogenates (p<0.001) and plasma (p<0.05) of the CS group but decreased in the
      BALF (p<0.001) and plasma (p<0.05) of the LPS group. GPx activity was reduced in
      the BALF (p<0.01) and plasma (p<0.01) of both the CS and LPS groups. Lipid
      peroxidation was increased in the BALF (p<0.001) and lung homogenates (p<0.001)
      of the CS group. Finally, the levels of nitrite were reduced in the CS (p<0.01)
      and LPS (p<0.001) groups. Our data show that the activity profiles of enzymes
      contributing to oxidant-antioxidant imbalance in the lungs differ depending on
      the inflammatory stimulus, and that SOD, CAT and GPx may be useful markers of
      oxidative stress in acute lung inflammation induced by exposure to CS.

PMID- 18721921
TI  - Histopathology-based combined surgical approach to rectovaginal endometriosis.
AB  - OBJECTIVE: To describe a new surgical approach to rectovaginal endometriosis.
      Rectovaginal endometriosis can be infiltrative or superficial involving the
      bowel. Only infiltrative disease should be treated by intestinal resection.
      However, infiltration of endometriosis cannot be confirmed by preoperative
      imaging techniques. METHODS: A total of 48 women with infiltrative rectovaginal
      endometriosis were included in this prospective study. Surgery was performed
      using a newly developed technique. All bowel resections were indicated according
      to operative findings and not on the basis of preoperative imaging technique
      results. RESULTS: The decision for rectosigmoidal resection was based on the
      results of the intraoperative dissection of the rectovaginal septum.
      Histologically, infiltration of the ventral bowel wall was confirmed in all
      cases. CONCLUSION: This new surgical technique for the treatment of rectovaginal
      endometriosis allows precise diagnosis and treatment with low morbidity. A
      resection of the mesorectum is not necessary because the endometriotic nodules
      are always located on the antimesenteric surface of the bowel.

PMID- 18721920
TI  - Biomarkers of kidney integrity in children and adolescents with dental amalgam
      mercury exposure: findings from the Casa Pia children's amalgam trial.
AB  - Mercury is toxic to the kidney, and dental amalgam is a source of mercury
      exposure. Few studies have evaluated the effects of dental amalgam on kidney
      function in a longitudinal context in children. Here, we evaluated urinary
      concentrations of glutathione S-transferases (GSTs) alpha and pi as biomarkers of
      renal proximal and distal tubular integrity, respectively, and albumin as a
      biomarker of glomerular integrity in children and adolescents 8-18 years of age
      over a 7-year course of dental amalgam treatment. Five hundred seven children, 8
      12 years of age at baseline, participated in a clinical trial to evaluate the
      neurobehavioral and renal effects of dental amalgam in children. Subjects were
      randomized to either dental amalgam or resin composite treatments. Urinary GSTs
      alpha and pi, albumin, and creatinine concentrations were measured at baseline
      and annually in all subjects. Results were evaluated using linear regression
      analysis. GST-alpha concentrations were similar between treatment groups and in
      each sex and race (white vs. non-white) group in each follow-up year. GST-pi
      levels tended upward over the course of follow-up by four- to six-fold. This
      increase was seen in all groups irrespective of the treatment, race, or gender.
      Females had GST-pi levels approximately twice those of males at all ages. Albumin
      concentrations were constant throughout the follow-up period and did not differ
      by treatment, although females had 39% higher albumin levels than males.
      Additionally, we found no significant effects of amalgam treatment on the
      proportion of children with microalbuminuria (>30 mg/g creatinine). These
      findings are relevant within the context of children's health risk assessment as
      relates to the safety of mercury exposure from dental amalgam on kidney function.
      These data also provide normative values for sensitive indices of renal
      functional integrity that may serve in the evaluation of children and adolescents
      with renal disorders.

PMID- 18721922
TI  - The impact of social support and sense of coherence on health-related quality of
      life among nursing home residents--a questionnaire survey in Bergen, Norway.
AB  - BACKGROUND AND OBJECTIVES: Few studies have examined the association between
      social support and health-related quality of life (HRQOL) among nursing home
      residents and whether the sense of coherence (SOC) modifies the effect of social
      support on health-related quality of life. The main aims of this study were to
      determine the relationship between social support and HRQOL and to investigate
      whether the SOC modifies the effect of social support on HRQOL. DESIGN: A cross
      sectional, descriptive, correlational design. SETTINGS: All 30 nursing homes in
      Bergen in western Norway. PARTICIPANTS: Two hundred and twenty-seven mentally
      intact long-term nursing home residents 65 years and older. METHODS: Data were
      obtained through face-to-face interviews using the SF-36 Health Survey, Social
      Provisions Scale and Sense of Coherence Scale. Possible relationships between the
      Social Provisions Scale and the eight SF-36 subdimensions were analysed using
      multiple linear regression while controlling for age, sex, marital status,
      education and comorbid illness. Interactions between the Sense of Coherence Scale
      and Social Provisions Scale were investigated. RESULTS: Attachment affected the
      mental health subdimension (p=0.001), opportunity for nurturance affected social
      functioning (p=0.003) and reassurance of worth affected vitality (p=0.001) after
      adjustment for demographic variables and comorbid illness. After the analysis
      included the sense of coherence, nurturance still significantly affected social
      functioning and reassurance of worth still significantly affected vitality. No
      interaction with sense of coherence was found, and sense of coherence
      significantly affected all SF-36 subdimensions. CONCLUSIONS: The opportunity to
      provide nurturance for others appears to be important for social functioning, and
      sense of competence and sense of self-esteem appear to be important for vitality.
      Further, the residents' relationships with significant others comprise an
      important component of mental health. Finally, independent of the level of sense
      of coherence, social support is an important resource for better health-related
      quality of life. Clinical nurses should recognize that social support is
      associated with health-related quality of life and pay attention to the
      importance of social support for the residents in daily practice.

PMID- 18721923
TI  - The nursing contribution to chronic disease management: a discussion paper.
AB  - This paper explores the nature of the nursing contribution to chronic disease
      management (CDM) and identifies a number of key nursing activities within CDM
      both at the individual patient and care system levels. The activities were
      identified following a detailed review of the literature (160 reports and studies
      of nursing practice) relating to three tracer disorders: diabetes, chronic
      obstructive pulmonary disease and multiple sclerosis. The paper examines these
      activities collectively to generate models expressing some of the core functions
      of nursing within CDM. The paper illustrates some of the changing characteristics
      of nursing roles within CDM. More fundamentally, the paper questions the position
      of nursing in relation to the technologies that define CDM systems and proposes
      four levels of contribution: the nurse as technology; the nurse as technologist;
      the nurse as system engineer; and the nurse as architect. These different levels
      reflect distinctions in the nature of the nursing gaze and power relations within
      the health care workforce. The paper also highlights how nurses are failing to
      develop the evidence for their practice in CDM. The paper concludes that there is
      a need for some clear principles to guide clinical practice and encourage
      innovation in CDM. It is argued that the principles should not be rule-bound but
      define a distinctive nursing gaze that will position the nursing profession
      within the health care system and in relation to other professions. The gaze
      should incorporate the needs of the individual patient and the care system that
      they inhabit.

PMID- 18721924
TI  - Improved efficiency in micellar liquid chromatography using triethylamine and 1
      butanol as mobile phase additives to reduce surfactant adsorption.
AB  - The effect of triethylamine as a mobile phase modifier on chromatographic
      efficiency in micellar liquid chromatography (MLC) is reported for nine different
      columns with various bonded stationary phases and silica pore sizes, including
      large-pore short alkyl chain, non-porous, and perfluorinated. Reduced plate
      height (h) versus reduced velocity (nu) plots were constructed for each column
      and the A' and C' terms calculated using a simplified Van Deemter equation
      introduced in our previous work. To further explore the practicality of using
      triethylamine in the micellar mobile phase, the efficiency of nine polar and non
      polar substituted benzenes was studied on seven columns. Surfactant adsorption
      isotherms were measured for five columns with three micellar mobile phases to
      understand the relationship between adsorbed surfactant, mobile phase additive,
      and column efficiency. Clear improvements in efficiency were observed with the
      addition of 2% (v/v) triethylamine to a 1-butanol modified aqueous micellar
      mobile phase. This finding is supported by the lower amount of surfactant
      adsorbed onto the stationary phase when TEA is present in the mobile phase
      compared to an SDS only or a 1-butanol modified SDS mobile phase.

PMID- 18721925
TI  - Ion-pair liquid-liquid-liquid microextraction of nerve agent degradation products
      followed by capillary electrophoresis with contactless conductivity detection.
AB  - The four nerve agent degradation products methylphosphonic acid (MPA), ethyl
      methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA) and
      cyclohexyl methylphosphonic acid (CMPA) have been successfully extracted from
      aqueous sample solution by ion-pair liquid-liquid-liquid microextraction. In this
      procedure, the target analytes in the sample solution were converted into their
      ion-pair complexes with tri-n-butyl amine and then extracted by an organic
      solvent (1-octanol) layer on top of the sample solution. Simultaneously, the
      analytes were back-extracted into a drop of an aqueous acceptor solution which
      was suspended in the organic phase at a microsyringe needle tip. The factors
      influential to extraction: type of organic solvent, type of ion-pair reagent and
      its concentration, pH values of sample solution and acceptor aqueous phase,
      stirring rate and extraction time were investigated in detail. After extraction,
      the drop of the acceptor solution was withdrawn into the syringe and injected
      into a capillary electrophoresis system for analysis. Using contactless
      conductivity detection, direct quantification of these compounds is possible.
      Moreover, large-volume sample injection was employed for further
      preconcentration. Improvements in the limits of detection between 2.5 and 4
      orders of magnitude could be achieved and concentrations at the ng/mL level can
      be determined. This newly established approach was successfully applied to a
      spiked river water sample.

PMID- 18721926
TI  - Unloaded rat hearts in vivo express a hypertrophic phenotype of cardiac
      repolarization.
AB  - Cardiac unloading with left ventricular assist devices is increasingly used to
      treat patients with severe heart failure. Unloading has been shown to improve
      systolic and diastolic function, but its impact on the repolarization of left
      ventricular myocytes is not known. Unloaded hearts exhibit similar patterns of
      gene expression as hearts subjected to an increased hemodynamic load. We
      therefore hypothesized that cardiac unloading also replicates the alterations in
      action potential and underlying repolarizing ionic currents found in pressure
      overload induced cardiac hypertrophy. Left ventricular unloading was induced by
      heterotopic heart transplantation in syngenic male Lewis rats. Action potentials
      and underlying K+ and Ca2+ currents were investigated using whole-cell patch
      clamp technique. Real-time RT-PCR was used to quantify mRNA expression of Kv4.2,
      Kv4.3, and KChIP2. Unloading markedly prolonged cardiac action potentials and
      suppressed the amplitude of several repolarizing K+ currents, in particular of
      the transient outward K+ current I(to), in both, epicardial and endocardial
      myocytes. The reduction of I(to) was associated with significantly lower levels
      of Kv4.2 and Kv4.3 mRNAs in epicardial myocytes, and of KChIP2 mRNA in
      endocardial myocytes. Concomitantly, the L-type Ca2+ current was increased in
      myocytes of unloaded hearts. Collectively, these results show that left
      ventricular unloading induces a profound remodelling of cardiac repolarization
      with action potential prolongation, downregulation of repolarizing K+ currents
      and upregulation of the L-type Ca2+ current. This indicates that unloaded rat
      hearts in vivo express a hypertrophic phenotype of cardiac repolarization at the
      cellular and the molecular level.

PMID- 18721927
TI  - Polyvinyl alcohol gel prevents adhesion re-formation after adhesiolysis in a
      rabbit model.
AB  - BACKGROUND: Chronic pain, infertility, and bowel obstructions are possible
      consequences of abdominal adhesions, which can highly affect the patient's
      quality of life. Patients in whom adhesiolysis has been performed are at high
      risk for recurrence of adhesions. For that reason, the present study focused on
      the re-formation of adhesions after adhesiolysis and on the possibility of
      avoiding it by using the adhesion barrier polyvinyl alcohol (PVA)-gel. MATERIALS
      AND METHODS: A randomized controlled study was conducted to prove the
      effectiveness of PVA-gel in reducing postoperative adhesion re-formation after
      relaparotomy. Moreover, ultrasound was evaluated as a noninvasive technique to
      determine abdominal adhesion in a rabbit model. All animals underwent an initial
      laparotomy to cause adhesions and subsequent adhesiolysis in the relaparotomy.
      PVA-gel was placed onto a side wall defect in 12 animals. Another 12 rabbits
      served as a control group without PVA-gel being used. Ultrasound before final
      laparotomy was performed to predict the prevalence of adhesions. Macroscopic
      evaluation of adhesion formation and planimetry were used to determine the amount
      of adhesion. RESULTS: PVA-gel was found to reduce significantly the amount of
      adhesion formation after relaparotomy (P = 0.0001) in comparison with the control
      group. Here severe adhesion formation was found to develop. The positive
      predictive value (100%) for adhesion evaluation using ultrasound is highly
      satisfying in the rabbit model. CONCLUSIONS: Adhesion re-formation after
      relaparotomy was found to decrease significantly through the use of PVA-gel.
      Ultrasound as a noninvasive technique of adhesion detection is a sufficient and
      reliable method for detecting adhesion formations.

PMID- 18721928
TI  - ALSFRS-R score and its ratio: a useful predictor for ALS-progression.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder.
      To determine predictors of survival, we studied different parameters in our ALS
      Database including 479 patients. The effects of individual prognostic factors of
      survival were studied using Kaplan-Meier life table. The prognostic value of each
      factor of interest was expressed in terms of a hazard ratio. Survival from
      symptom-onset ranged from 4 months up to 11.9 years. Gender had no effect on
      survival in our cohort. However, age, site of onset, forced vital capacity,
      symptom duration and ALSFRS-R score at the first visit were independent
      prognostic factors in our population (log-rank p<0.01). The ratio of ALSFRS-R
      score between first symptom and first examination, during whole disease or within
      100 days, correlates with survival time. We conclude that the ratio of ALSFRS-R
      score within 100 days is a useful parameter for clinical trials and daily
      clinical work in a tertiary ALS-clinic.

PMID- 18721930
TI  - Aberrant expression of ovary determining gene FOXL2 in the testis and juvenile
      granulosa cell tumor in children.
AB  - PURPOSE: FOXL2 is the earliest known marker of ovarian differentiation in
      mammals. It is involved in ovarian somatic cell differentiation and further
      follicle maintenance. FOXL2 is not implicated in determination of the male gonad
      and it is absent in the testis. We investigated whether the rare JGCTT (juvenile
      granulose cell tumor of the testis), named for its histological similarity to
      ovarian tumor, could be the first illustration of aberrant expression of this
      ovary determining gene in the human testis. MATERIALS AND METHODS: Between 1990
      and 2004, 3 boys with JGCTT were reported from the TGM95 database of the French
      Society for Childhood Cancer and from 8 pediatric endocrinology centers.
      Orchiectomy was performed in these patients. Immunohistochemistry of FOXL2, and
      co-immunofluorescence of FOXL2 and SOX9 were performed on tumor sections.
      RESULTS: Testicular tumor cells showed aberrant expression of FOXL2, which
      resembled normal ovarian granulosa cells. The localization of FOXL2 expression
      was nuclear without any cytoplasmic sequestration, suggesting that FOXL2 had
      biological activity. Conversely SOX9, which is present in the nucleus of normal
      testicular cells, was sequestered in the cytoplasm of granulosa tumor cells or
      markedly under expressed in the nuclei. In this case of residual SOX9 nuclear
      expression the expression of FOXL2 and SOX9 was mutually exclusive. CONCLUSIONS:
      To our knowledge we report the first human model of aberrant intratesticular
      expression of an ovary determining gene along with the extinction of SOX9 and the
      transdifferentiation of a testicular cell into a granulosa tumor cell.

PMID- 18721933
TI  - A new computer enhanced visual learning method to train urology residents in
      pediatric orchiopexy: a prototype for Accreditation Council for Graduate Medical
      Education documentation.
AB  - PURPOSE: Residency programs must continue to restructure teaching and assessment
      of surgical skills to improve the documentation of Accreditation Council for
      Graduate Medical Education competencies. To improve teaching and documenting
      resident performance we developed a computer enhanced visual learning method that
      includes a curriculum and administrative reports. The curriculum consists of 1)
      study of a step-by-step surgical tutorial of computer enhanced visuals that show
      specific surgical skills, 2) a checklist tool to objectively assess resident
      performance and 3) a log of postoperative feedback that is used to structure
      deliberate practice. All elements of the method are repeated with each case
      performed. We used the Accreditation Council for Graduate Medical Education index
      case of orchiopexy to pilot this project. MATERIALS AND METHODS: All urology
      residents who trained at our institution from January 2006 to October 2007
      performed orchiopexy using the computer enhanced visual learning method. The
      computer enhanced visual learning tutorial for orchiopexy consisted of customized
      computer visuals that demonstrate 11 steps or skills involved in routine inguinal
      orchiopexy, eg ligate hernia. The attending urologist rated resident competence
      with each skill using a 5-point Likert scale and provided specific feedback to
      the resident suggesting ways to improve performance. These ratings were weighted
      by case difficulty. The computer enhanced visual learning weighted score at entry
      into the clinical rotation was compared to the best performance during the
      rotation in each resident. RESULTS: Seven attending surgeons and 24 urology
      residents (resident training postgraduate years 1 to 8) performed a total of 166
      orchiopexies. Overall the residents at each postgraduate year performed an
      average of 7 cases each with complexity ratings that were not significantly
      different among postgraduate year groups (average 2.4, 1-way ANOVA p not
      significant). The 7 attending surgeons did not differ significantly in assessment
      of skill performance or case difficulty (1-way ANOVA p not significant). Of the
      24 residents 23 (96%) showed improvement in computer enhanced visual learning
      score/skill performance. In the entire group the average computer enhanced visual
      learning weighted score increased more than 50% from entry to best performance
      (137 to 234 orchiopexy units, paired t test p <0.0001). CONCLUSIONS: Computer
      enhanced visual learning is a novel method that enhances resident learning by
      breaking a core procedure into discrete steps and providing a platform for
      constructive feedback. Computer enhanced visual learning, which is a checklist
      tool, complies with Accreditation Council for Graduate Medical Education
      documentation requirements. Computer enhanced visual learning has wide
      applicability among surgical specialties.

PMID- 18721934
TI  - Persistent motor deficits predict long-term bladder dysfunction in children
      following acute transverse myelitis.
AB  - PURPOSE: We determined whether motor and bladder recovery are correlated in
      children with acute transverse myelitis. MATERIALS AND METHODS: From 1995 to
      2004, 14 children (8 males and 6 females) with acute transverse myelitis were
      retrospectively evaluated to determine if there was a correlation between motor
      and bladder recovery following disease onset. RESULTS: During the acute phase of
      the disease, all patients experienced lower extremity motor deficit and bladder
      dysfunction. Full motor recovery was associated with full bladder recovery, and
      no motor recovery was related to no bladder recovery. Partial motor recovery was
      associated with either no or partial bladder recovery. CONCLUSIONS: Motor and
      bladder recovery were related in our patients with transverse myelitis. Children
      with no motor recovery did not experience bladder recovery. No significant
      bladder recovery was seen beyond 4 months in our patients.

PMID- 18721936
TI  - Extravesical ureteral reimplantation: an outpatient procedure.
AB  - PURPOSE: We determined whether implementation of a critical pathway and
      modification of the extravesical ureteral reimplantation surgical technique to
      repair unilateral and bilateral vesicoureteral reflux would consistently result
      in same day patient hospital discharge without increased morbidity. MATERIALS AND
      METHODS: We evaluated all children undergoing extravesical ureteral
      reimplantation using a modified technique that limits ureteral dissection,
      ureteral mobilization and detrusor dissection to as distal as possible. No
      surgical dissection is done in proximity to the obliterated umbilical artery, nor
      is the artery ligated. Patients follow a strict postoperative critical pathway,
      and parents receive extensive preoperative and postoperative education. The child
      is required to fulfill strict criteria to be discharged home. RESULTS: A total of
      51 girls and 9 boys 0.9 to 10.5 years old (mean age 5.1) were evaluated. A total
      of 24 unilateral and 36 bilateral procedures were performed with and without
      ureteral tapering, and for single systems, duplex systems and an associated Hutch
      diverticulum. Overall 54 children (90%) were discharged home the same day, while
      only 6 (10%) went home the next day. All patients who underwent a unilateral
      procedure and 83% who underwent a bilateral procedure were outpatients. However,
      when evaluating the last 40 consecutive patients, including 14 with a unilateral
      and 26 with a bilateral procedure, all (100%) were discharged home the day of
      surgery without increased morbidity or an additional analgesic requirement. All
      outpatients were discharged within 5 hours after surgery. All patients tolerated
      the procedure well without major complications and without any patients requiring
      an emergency department visit or hospitalization after discharge home. After the
      urinary catheter was removed all patients were able to spontaneously void
      postoperatively without any acute or chronic urinary retention. CONCLUSIONS: This
      study demonstrates that implementation of a strict critical pathway and a
      unilateral or bilateral extravesical ureteral reimplantation surgical technique
      with limited dissection can consistently result in same day discharge from the
      hospital within a few hours postoperatively without increased morbidity or
      rehospitalization.

PMID- 18721937
TI  - Intermittent torsion of the spermatic cord portends an increased risk of acute
      testicular infarction.
AB  - PURPOSE: Intermittent torsion of the spermatic cord is an episode of acute
      torsion of the spermatic cord that resolves spontaneously. We compared the
      outcomes in boys with intermittent spermatic cord torsion treated electively with
      testicular fixation with those in boys with a history of recurrent scrotal pain
      who required emergent operation for acute spermatic cord torsion without
      spontaneous resolution. MATERIALS AND METHODS: A retrospective review revealed 17
      boys who required emergency operation for acute spermatic cord torsion and 30 who
      underwent elective surgery for intermittent spermatic cord torsion. The clinical
      presentation, number of recurrent painful episodes, lead time to operation, prior
      alternate diagnoses, intraoperative findings and clinical outcomes were recorded.
      RESULTS: There was a mean of 2 recurrent painful episodes in the elective group
      and 3 in the emergency group (p <0.005). In the elective group all boys were
      cured of pain after bilateral testicular fixation with 100% testicular
      preservation at a mean of 4 months of followup. In the emergency group at a mean
      of 10 months of followup the testicular preservation rate was 47% (p <0.01).
      Intraoperatively an ipsilateral bell clapper malformation was found in 100% of
      boys in each group. A contralateral bell clapper malformation was noted in 90%
      and 88% of boys in the elective and emergency groups, respectively. CONCLUSIONS:
      When diagnosed accurately, intermittent spermatic cord torsion can be treated
      with elective testicular fixation with an excellent outcome. Misdiagnosis may
      create a cohort of boys with intermittent spermatic cord torsion who are at risk
      for acute unresolved torsion and potential testicular loss. Urologists should be
      proactive in recommending elective scrotal exploration when intermittent
      spermatic cord torsion is a likely diagnosis.

PMID- 18721938
TI  - Management of urachal remnants in early childhood.
AB  - PURPOSE: Generally, it is recommended that all urachal remnants be excised to
      avoid recurrent disease and possible malignant transformation later in life.
      However, spontaneous resolution with no need for further intervention has been
      reported. We reviewed the experience with urachal remnants at a single
      institution and evaluated which patients could be treated nonoperatively and
      which required surgical intervention. MATERIALS AND METHODS: We reviewed the
      medical records and radiographic studies of all patients with urachal remnants
      from January 1999 to January 2007. Patients were analyzed according to initial
      presentation, imaging findings and treatment. Serial clinical examinations and
      radiographic imaging were used to follow patients. RESULTS: An external urachal
      sinus was found in 9 patients (39.1%) and 1 was surgically excised. Of the 12
      urachal cysts (52.2%) 9 ultimately required surgical excision, of which 6 were
      infected initially. A patent urachus was found in 2 patients, which resolved
      during an observation period. Radiographic imaging and/or physical examination
      diagnosed all remnants initially and confirmed complete resolution during
      followup. Eight of the 10 urachal remnants (80.0%) that resolved developed in
      patients younger than 6 months. Various accompanying urogenital anomalies were
      found in 8 patients (34.8%). CONCLUSIONS: A small urachal remnant, especially at
      birth, may be viewed as physiological. Urachal remnants in patients younger than
      6 months are likely to resolve with nonoperative management. However, if symptoms
      persist or the urachal remnant fails to resolve after 6 months of age, it should
      be excised to prevent recurrent infections.

PMID- 18721940
TI  - Testicular histology in boys with Prader-Willi syndrome: fertile or infertile?
AB  - PURPOSE: Prader-Willi syndrome is associated with hypogonadism. Cryptorchidism is
      found in 93% of cases and considered a phenotypic criterion. Men with Prader
      Willi syndrome are thought to be infertile. To study the fertility probability in
      boys with Prader-Willi syndrome we analyzed testicular histology in 8 prepubertal
      boys and 1 man. MATERIALS AND METHODS: Eight boys 16 months to 14 years old with
      a proven molecular diagnosis of Prader-Willi syndrome, including 6 with a
      deletion on chromosome 15 and 2 with uniparental maternal disomy of chromosome
      15, underwent orchiopexy and the man underwent unilateral orchiectomy.
      Prepubertal testes were classified into 4 Nistal categories according to mean
      tubular diameter, the tubular fertility index (average percent of tubules
      containing spermatogonia) and the Sertoli's cell index. RESULTS: Two of 8
      prepubertal boys showed a favorable Nistal score of I, 1 showed a Nistal score of
      II and 5 showed a Nistal score of III. The testis in the man showed diffuse
      tubular atrophy with tubular hyalinization, a Sertoli's cell nodule, vacuolized
      Leydig cells, peritubular hyalinization and small tubuli. CONCLUSIONS: Prader
      Willi syndrome appears to be a heterogenic disorder with respect to testicular
      histology. Although most boys showed absent spermatogonia, 2 of 8 had normal
      testicular histology. Therefore, it is suggested that it is uncertain what the
      fertility outcome is in boys with Prader-Willi syndrome.

PMID- 18721942
TI  - Directed differentiation of bone marrow derived mesenchymal stem cells into
      bladder urothelium.
AB  - PURPOSE: We have previously reported that embryonic rat bladder mesenchyma has
      the appropriate inductive signals to direct pluripotent mouse embryonic stem
      cells toward endodermal derived urothelium and develop mature bladder tissue. We
      determined whether nonembryonic stem cells, specifically bone marrow derived
      mesenchymal stem cells, could serve as a source of pluripotent or multipotent
      progenitor cells. MATERIALS AND METHODS: Epithelium was separated from the
      mesenchymal shells of embryonic day 14 rat bladders. Mesenchymal stem cells were
      isolated from mouse femoral and tibial bone marrow. Heterospecific recombinant
      xenografts were created by combining the embryonic rat bladder mesenchyma shells
      with mesenchymal stem cells and grafting them into the renal subcapsular space of
      athymic nude mice. Grafts were harvested at time points of up to 42 days and
      stained for urothelial and stromal differentiation. RESULTS: Histological
      examination of xenografts comprising mouse mesenchymal stem cells and rat
      embryonic rat bladder mesenchyma yielded mature bladder structures showing normal
      microscopic architecture as well as proteins confirming functional
      characteristics. Specifically the induced urothelium expressed uroplakin, a
      highly selective marker of urothelial differentiation. These differentiated
      bladder structures demonstrated appropriate alpha-smooth muscle actin staining.
      Finally, Hoechst staining of the xenografts revealed nuclear architecture
      consistent with a mouse mesenchymal stem cell origin of the urothelium,
      supporting differentiated development of these cells. CONCLUSIONS: In the
      appropriate signaling environment bone marrow derived mesenchymal stem cells can
      undergo directed differentiation toward endodermal derived urothelium and develop
      into mature bladder tissue in a tissue recombination model. This model serves as
      an important tool for the study of bladder development with long-term application
      toward cell replacement therapies in the future.

PMID- 18721943
TI  - Temporal-spatial protein expression in bladder tissue derived from embryonic stem
      cells.
AB  - PURPOSE: Identifying developmental proteins could lead to markers of bladder
      progenitor cells, which could be used to investigate bladder diseases. We
      recently reported a novel embryonic stem cell model in which to study
      differential protein expression patterns during bladder development. Differential
      and temporal expressions of the endodermal proteins known as forkhead box (Foxa1
      and Foxa2) were observed. In the current study we further delineated these
      protein expression patterns. MATERIALS AND METHODS: Epithelium was removed from
      the underlying mesenchyma from embryonic day 18 rat bladders. Heterospecific
      recombinant xenografts were created by combining embryonic stem cells plus
      embryonic bladder mesenchyma and placed beneath the renal capsule of mouse hosts.
      Grafts were harvested at 16, 18, 21, 28, 35 and 42 days, and evaluated with
      hematoxylin and eosin, trichrome staining, and immunohistochemistry for
      uroplakin, smooth muscle alpha-actin, p63, Foxa1, Foxa2 and androgen receptor.
      RESULTS: At 16 days uroplakin was detectable and it seemed to correlate with the
      loss of Foxa2, while Foxa1 remained at all time points. Androgen receptor was
      first noted in stroma at day 16. It localized to urothelial nuclei at day 21 and
      was undetectable at 42 days. Adjacent to the urothelium alpha-smooth muscle actin
      was seen on day 16 and it was localized in bundles to the periphery of the graft
      at later time points. Staining for basilar urothelium with p63 confirmed basilar
      orientation at all time points. CONCLUSIONS: We report the temporal spatial
      expression of various genes in early bladder development. This suggests that some
      proteins may be potential markers of bladder progenitor cells. Characterizing
      these markers may potentially identify bladder progenitor cells that have been
      directed toward a lineage path destined to become urothelial cells. Ultimately
      these multipotential progenitor cells could be isolated and used to study and
      treat diseases that affect the bladder.

PMID- 18721945
TI  - Buccal mucosa grafts for repair of stenotic catheterizable continent stoma.
AB  - PURPOSE: Different tubular structures have been used to create cutaneous
      catheterizable continent urinary stomas. The most common complication is stomal
      stenosis on the cutaneous end of the tubes. We present a variant of stomal
      stenosis repair that uses a buccal mucosa graft. MATERIALS AND METHODS: Between
      January 2000 and March 2006 stenotic stomal repair was performed in 10 patients
      between 3 and 17 years old (mean age 6). A Mitrofanoff channel was created from a
      bladder tube in 4 patients, from appendix in 3, from ileum in 2 and from the
      ureter in 1. The procedure involved the removal of scar tissue and the creation
      of well vascularized dermal beds by skin de-epithelialization (epidermis
      removal). After that we formed 2 elliptical dermal flaps. Two elliptical buccal
      mucosa grafts were quilted to the recipient bed (the dermal flap) and anastomosed
      with the mucosa of the normal part of the channel. The flaps were joined,
      tubularized and sutured to the skin. An indwelling catheter was left in the
      channel for 2 weeks. Postoperatively the buccal mucosa was wetted with saline
      solution for 4 consecutive days. RESULTS: Followup was between 12 and 39 months
      (mean 22). There was no partial or total graft necrosis. None of the patients
      experienced repeat stenosis. The stoma was visible (uncovered) and the esthetic
      appearance was satisfactory in all patients. CONCLUSIONS: Repair of Mitrofanoff
      stomal stenosis using a buccal mucosa graft is a minor procedure. It is a good
      salvage procedure that excludes the need to create a new channel.

PMID- 18721946
TI  - When is prior ureteral stent placement necessary to access the upper urinary
      tract in prepubertal children?
AB  - PURPOSE: We studied the possibility that age, height, weight and body mass index
      could be used to predict the likelihood of successful ureteroscopic access to the
      upper urinary tract without previous stent placement in prepubertal children.
      MATERIALS AND METHODS: We retrospectively reviewed all ureteroscopic procedures
      for upper tract calculi in prepubertal children from 2003 to 2007. We compared
      age, height, weight and body mass index in patients who underwent successful
      primary flexible ureteroscopic access and in those who required initial stent
      placement to perform ureteroscopy. RESULTS: Successful primary ureteroscopic
      access to the upper tract was achieved in 18 of 30 patients (60%). There was no
      difference in mean age (9.9 vs 9.5 years, p = 0.8), height (132 vs 128 cm, p =
      0.6), weight (37 vs 36 kg, p = 0.86) or body mass index (19.3 vs 20.5 kg/m(2), p
      = 0.55) between patients with successful vs unsuccessful upper tract access.
      Locations that prevented access to the upper urinary tract were evenly
      distributed among the ureteral orifice, iliac vessels and ureteropelvic junction.
      CONCLUSIONS: Age, height, weight and body mass index could not predict the
      likelihood of successful ureteroscopic access to the upper tract. Placement of a
      ureteral stent for passive ureteral dilation is not necessary for successful
      ureteroscopic access to the renal pelvis in prepubertal children. An initial
      attempt at ureteroscopy, with placement of a ureteral stent if upper tract access
      is unsuccessful, decreases the number of procedures while maintaining a low
      complication rate.

PMID- 18721947
TI  - Parenchymal echo texture predicts testicular salvage after torsion: potential
      impact on the need for emergent exploration.
AB  - PURPOSE: In the setting of signs and symptoms of testicular torsion the absence
      of diastolic flow and/or color flow on Doppler ultrasound has traditionally
      prompted emergent scrotal exploration. This practice emanates largely from the
      difficulty on ultrasound of distinguishing salvageable torsed testes from those
      that are not salvageable. We identified ultrasound findings predictive of
      testicular viability or the lack thereof. MATERIALS AND METHODS: We
      retrospectively reviewed the charts of all boys who underwent scrotal exploration
      for signs and symptoms of torsion during a 4-year period. In those who underwent
      preoperative Doppler ultrasound of the scrotum ultrasound findings were reviewed,
      as were the operative dictations. In patients who underwent orchiectomy the
      pathology reports were also reviewed. In patients in whom the torsed testis
      appeared viable and who underwent orchiopexy followup data were reviewed when
      available. Emergency room charts were also reviewed to ascertain, when
      documented, the duration of pain before presentation to the emergency room and
      the interval between ultrasound and operating room. RESULTS: During this period
      55 boys underwent exploration after preoperative scrotal Doppler ultrasound
      revealed absent diastolic flow and/or color flow Doppler in the symptomatic
      testis. Assessment of parenchymal echogenicity revealed heterogeneity in 37
      testes (67%), of which none were deemed viable at exploration. Orchiectomy was
      performed in 34 of 37 cases. Pathological examination revealed necrosis in all 34
      cases, a finding consistent with late torsion. The remaining 3 testes underwent
      orchiopexy by parental directive despite nonviability, as confirmed by biopsy and
      subsequent atrophy. Thus, heterogeneity on preoperative ultrasound was
      universally predictive of organ loss (chi-square p <0.001). Of the 18 symptomatic
      testes (33%) demonstrating homogeneity and isoechogenicity on ultrasound 16 (89%)
      were deemed viable at exploration. Boys in whom the torsed testicle was nonviable
      on exploration experienced an average of 27.5 hours of pain preoperatively (range
      5 to 72), whereas boys in whom the torsed testis was salvaged experienced an
      average of 20.5 hours of pain (range 2 to 96) (p = 0.073). The nonviable group
      underwent surgery an average of 49 minutes after ultrasound, whereas the viable
      group underwent surgery 52 minutes after ultrasound (p = 0.92). None of the 55
      patients experienced any surgical or anesthetic complications and no pathological
      condition was noted intraoperatively in the contralateral asymptomatic testis.
      CONCLUSIONS: In the setting of Doppler proven testicular torsion heterogeneous
      parenchymal echo texture indicates late torsion and testicular nonviability.
      Therefore, the case may not require emergent scrotal exploration. On the other
      hand, homogeneous echo texture portends extremely well for testicular viability.
      Thus, such testes should be explored emergently.

PMID- 18721951
TI  - Tap water irrigation and additives to optimize success with the Malone antegrade
      continence enema: the Indiana University algorithm.
AB  - PURPOSE: We report the long-term effectiveness of standard tap water for Malone
      antegrade continence enema irrigation as well as our algorithm for managing
      refractory constipation/fecal incontinence in a large single institution
      experience. MATERIALS AND METHODS: We retrospectively reviewed the charts of 256
      Malone antegrade continence enema procedures performed for chronic constipation
      and/or incontinence due to neuropathic bowel. Continence, type of fluid used to
      irrigate the colon, volume of flushes and the need for additives were recorded
      and a database was created. All patients were initially treated with tap water
      irrigation. Those in whom tap water irrigation failed underwent complete bowel
      cleanout with enemas and GoLYTELY via the Malone antegrade continence enema,
      followed by a gradual increase in irrigation volume. If this was unsuccessful,
      additives of mineral oil, MiraLAX or glycerin were added to the irrigant daily.
      RESULTS: A total of 236 patients with at least 6 months of followup were included
      in this study. Mean age at surgery was 10.2 years (range 2 to 36) and mean
      followup in the entire cohort was 50 months (range 6 to 115). Mean volume of
      colonic flushes was 642 ml (range 100 to 1,000). Of the patients 196 (83.1%)
      achieved total fecal continence with tap water flushes alone. Using additives
      increased the overall continence rate to 93.6% (p <0.0001). CONCLUSIONS: The
      Malone antegrade continence enema procedure has proved invaluable for treating
      children with refractory constipation. When additives are used in conjunction
      with water flushes, they can significantly improve the overall fecal continence
      rate in partially continent children.

PMID- 18721952
TI  - Complications of the catheterizable channel following continent urinary
      diversion: their nature and timing.
AB  - PURPOSE: We reviewed the incidence, nature and timing of complications related to
      the catheterizable channel following continent urinary diversion. MATERIALS AND
      METHODS: We retrospectively reviewed the records of 67 patients who underwent
      continent urinary diversion at British Columbia Children's Hospital from 2000 to
      2006. Catheterizable channels included 54 Mitrofanoff appendicovesicostomies and
      13 ileovesicostomies. Medical records were reviewed for predetermined
      complications and their timing, that is early -12 months or less, or late - more
      than 12 months. RESULTS: At a median followup of 28 months (range 3 to 62) a
      total of 17 complications were identified in 14 patients (21%). Superficial
      cutaneous stenosis developed in 4 of 67 cases (6%) as an early and as a late
      complication. These cases were initially treated with operative dilation and
      surgical revision as necessary. Channel stricture, which developed in 4 of 67
      patients (6%) as an early and as a late complication, was treated with operative
      revision in 2 and endoscopic resection in 2. Three patients (5%) had stomal
      prolapse, which was generally a late occurrence and required operative revision
      in all. Channel leakage developed in 6 of 67 patients, presenting as an early
      complication in 50%. Endoscopic injection of bulking agents was attempted in 4 of
      these patients and it was successful in 2. Overall 82% of complications were
      successfully managed by endoscopic or superficial procedures. CONCLUSIONS:
      Complications of the catheterizable channel are a frequent and challenging
      problem. They appear to occur throughout the life of the channel with most
      developing within the first 2 years. Further followup is required to assess the
      performance and durability of continent catheterizable channels in children as
      patients progress to adulthood.

PMID- 18721953
TI  - A review of pediatric glans malformations: a handy clinical reference.
AB  - PURPOSE: Lesions of the pediatric glans penis are an uncommon but important
      aspect of pediatric urological care. We reviewed the available literature on this
      topic and did not identify a comprehensive reference resource. We compiled our
      multi-institutional experience with such conditions to prepare a handy clinical
      reference source. MATERIALS AND METHODS: The diversity of pediatric glans penis
      lesions was documented by searching the English and nonEnglish literature as well
      as the archives at our institutions. Cases were included in the study if the
      patient(s) identified were younger than 18 years at initial presentation or
      documented to have first had a glans penis lesion when younger than 18 years.
      Hypospadiac-epispadiac anomalies of the glans were excluded. RESULTS: From our
      institutions we identified 6 new cases of various pediatric glans lesions.
      Altogether the literature describes 137 distinct nondiphallia glans lesions and
      more than 100 cases of diphallia, including glans duplication. The nondiphallia
      reports consist of a total of 61 cystic lesions (44%), 33 vascular malformations
      (24%), 20 dermatological lesions (15%), 20 infectious lesions (15%) and 3
      neurogenic lesions (2%). We did not identify a compact resource to compare these
      anomalies. Visual comparison permits structuring a differential diagnosis and
      determining urological treatment, which is typically excisional biopsy, laser
      treatment, sclerotherapy or topical steroid administration. CONCLUSIONS: We
      present a visual reference of varied lesions of the pediatric glans penis,
      including 6 new cases, with urological significance. These lesions are always
      benign but they typically require surgical excision for a definitive pathological
      diagnosis.

PMID- 18721954
TI  - Corporeal grafting for severe hypospadias: a single institution experience with 3
      techniques.
AB  - PURPOSE: Correction of severe chordee by corporeal body grafting has been
      successfully performed using various grafts and biomaterials. We report a single
      institution comparison of our experience using small intestinal submucosa, tunica
      vaginalis and dermal grafts at stage 1 hypospadias repair. MATERIALS AND METHODS:
      A retrospective chart review was performed of the records of all patients who
      underwent staged hypospadias repair from 1985 to 2006 with corporeal body
      grafting at stage 1 with small intestinal submucosa, tunica vaginalis or dermal
      grafts. Age at grafting, time between stages, residual chordee at stage 2 repair
      and the need for additional plication or chordee correction at stage 2 were
      recorded. RESULTS: A total of 71 patients were identified with a median age of 10
      months at stage 1 repair and a median of 7.6 months between stages 1 and 2
      repair. Dermal grafts, tunica vaginalis and small intestinal submucosa grafts
      were used in 29, 21 and 20 patients, respectively. One patient received a
      combination of small intestinal submucosa and tunica vaginalis. None of the
      patients receiving tunica vaginalis graft required any further correction of
      chordee. One patient with a dermal graft and 1 receiving small intestinal
      submucosa required Nesbit plication at stage 2 repair for minor ventral chordee.
      One patients receiving small intestinal submucosa showed severe fibrosis at the
      graft site, requiring excision and repeat grafting with tunica vaginalis. This
      patient has been previously described. The 2 patients with small intestinal
      submucosa related complications had 4-ply grafts. We have seen no complications
      associated with 1-ply small intestinal submucosa. At limited followup we have not
      seen residual chordee after stage 2 repair. CONCLUSIONS: In a large group of
      children requiring corporeal grafting for severe chordee we observed successful
      chordee correction with 1-ply small intestinal submucosa, tunica vaginalis or
      dermal grafts.

PMID- 18721959
TI  - Development and validation of the fecal incontinence and constipation quality of
      life measure in children with spina bifida.
AB  - PURPOSE: Fecal incontinence and constipation in children with spina bifida are
      recognized to impact quality of life. Most disease specific quality of life
      instruments on fecal incontinence target adults and/or children without
      neuropathic bowel. We developed an instrument to evaluate bowel function and its
      impact on quality of life in children with spina bifida and their caregivers.
      MATERIALS AND METHODS: A 51-item questionnaire termed the FIC QOL (Fecal
      Incontinence and Constipation Quality of Life) survey was developed from expert
      opinion, patient interviews, and modification of previously published adult and
      pediatric studies for nonneuropathic bowel dysfunction. The items are divided
      into 7 quality of life factor groupings, including bowel program, dietary
      management, symptoms, travel and socialization, family relationships, caregiver
      emotional impact and financial impact. The questionnaire was given to caregivers
      of children with and without spina bifida. Discriminant validity was evaluated by
      comparing the spina bifida and control groups. Test-retest reliability was
      evaluated by having 41 patients complete 2 surveys within 4 to 6 weeks. RESULTS:
      Comparing questionnaires from 92 index patients and 52 controls showed a
      statistically significant difference for all 7 quality of life factor groupings.
      The FIC QOL instrument objectively demonstrated the negative impact of fecal
      incontinence and constipation on quality of life in these families. Comparing 82
      questionnaires at 2 time points demonstrated the reliability of all FIC QOL
      questions. CONCLUSIONS: The FIC QOL instrument provides a valid and reliable
      measure of the effect of fecal incontinence and constipation on the quality of
      life of caregivers and their children with spina bifida.

PMID- 18721961
TI  - Ventral penile lengthening versus dorsal plication for severe ventral curvature
      in children with proximal hypospadias.
AB  - PURPOSE: The 2 main approaches to correct severe ventral curvature are dorsal
      plication of the corpora and ventral corporeal lengthening by tunica albuginea
      patching. Controversy persists since neither technique has been proved to be
      superior to the other with respect to initial or long-term outcome. However, to
      our knowledge a direct comparison of outcome of these 2 procedures has not been
      previously reported. MATERIALS AND METHODS: A retrospective review of the records
      of 100 consecutive patients who underwent repair of penoscrotal or more proximal
      defects from 1996 to 2004 was performed. Children were divided into 2 groups,
      including group 1-32 who underwent a ventral penile lengthening procedure and
      group 2-68 who underwent dorsal plication. Meatal location, preoperative
      testosterone stimulation, severe ventral curvature (greater than 45 degrees) at
      the beginning of operation and after degloving, proximal ventral dissection,
      urethral plate transection and recurrent ventral curvature were compared between
      the 2 groups. RESULTS: Mean age was 17 months (range 9 to 56) in patients with
      ventral penile lengthening and 17.8 months (range 10 to 58) in patients with
      dorsal plication. Mean followup was 65 (range 29 to 120) and 62 months (range 30
      to 116), respectively. Of the 32 group 1 children 30 (93.7%) had penoscrotal or
      more proximal hypospadias vs 57 of the 68 (83.8%) in group 2. Three of the 32
      children who underwent ventral penile lengthening had recurrent ventral curvature
      vs 19 of the 68 who underwent dorsal plication (9.4% vs 27.9%, p = 0.03). On
      multivariate analysis dorsal plication remained significantly associated with
      recurrent ventral curvature independently of the other factors (OR 4.56, 95% CI
      1.14-18.28, p = 0.03). CONCLUSIONS: Dorsal plication was more often associated
      with recurrent ventral curvature compared to ventral penile lengthening on
      univariate and multivariate analysis. Future studies adjusting for proximal
      ventral dissection and urethral plate transection are necessary to further
      elucidate the role of each technique in the correction of severe ventral
      curvature in children with proximal hypospadias.

PMID- 18721963
TI  - Results and complications of adolescent varicocele repair with intraoperative
      sodium morrhuate sclerotherapy.
AB  - PURPOSE: Adolescent varicocele has been shown to affect spermatogenesis and
      correlate with decreased ipsilateral testicular volume, prompting treatment in a
      select population. We report our experience with 3 varicocele ligation procedures
      in concordance with sclerotherapy in adolescent patients. MATERIALS AND METHODS:
      A total of 120 males underwent varicocele surgery at our institutions during an 8
      year period. Sodium morrhuate sclerotherapy was used in 91 patients and 73
      adolescent males fulfilled the 6-month followup criteria. The 73 males who were 9
      to 17 years old underwent a total of 75 (bilateral in 2) procedures for
      varicocele treatment. Of the patients 23 underwent subinguinal microscopic
      varicocelectomy (group 1), 9 underwent loupe assisted subinguinal varicocelectomy
      (group 2) and 41 underwent loupe assisted inguinal varicocelectomy (group 3). All
      patients received intraoperative sclerotherapy using sodium morrhuate injection.
      Outcome measures included recurrence, complications and catch-up growth at a
      minimum of 6 months of followup. RESULTS: The varicocele recurrence rate was 2.7%
      in patients receiving combined surgical ligation and sclerotherapy ablation.
      Group 1 had 2 recurrent varicoceles and no hydrocele formation, group 2 had no
      varicocele recurrence and no hydrocele formation, and group 3 had no varicocele
      recurrence and 2 postoperative hydroceles. Catch-up growth in the ipsilateral
      testis was seen in 85% of patients. No atrophy or testicular loss was noted.
      CONCLUSIONS: This preliminary experience with combined surgical ligation and
      sclerotherapy ablation in the adolescent population resulted in low varicocele
      recurrence with minimal morbidity. Outcomes of loupe assisted varicocelectomy
      appear to be improved compared to those in previous studies, alluding to an
      advantage in the addition of sclerotherapy.

PMID- 18721965
TI  - Clean intermittent catheterization in children through a continent catheterizable
      channel: a developing country experience.
AB  - PURPOSE: We evaluated the role of clean intermittent self-catheterization through
      a continent catheterizable Mitrofanoff channel in an augmented bladder in
      children with bladder dysfunction and outlet obstruction. MATERIALS AND METHODS:
      We retrospectively analyzed the records of 82 patients treated at a public sector
      hospital with pediatric urology services in a developing country. Patients came
      from all provinces of the country with diverse ethnic, cultural, linguistic,
      socioeconomic and educational backgrounds. RESULTS: Mean +/- SD patient age was
      9.07 +/- 3.38 years (range 2.5 to 15) with a male-to-female ratio 2.5:1.0. The
      main congenital and acquired abnormalities were posterior urethral valves in 29%
      of patients, neuropathic bladder in 22%, nonneurogenic neurogenic bladder in 17%,
      exstrophy plus epispadias in 10% and urethral stricture in 7%. Augmentation
      cystoplasty was performed using various bowel segments. The Mitrofanoff channel
      was made using appendix in 70 cases and by the spiral Monti method in 12. A stoma
      was created in the right iliac fossa using VQZ plasty in 72 patients and an
      umbilical stoma was created in 10. Complications included bladder calculus in 3
      patients, stomal stenosis in 2, subacute intestinal obstruction in 4 and acute
      intestinal obstruction in 1. Compliance was observed in greater than 90% of the
      patients at a mean followup of 860 days. CONCLUSIONS: In a developing country
      setting with a low socioeconomic and educational level it is possible to
      successfully perform augmentation cystoplasty with clean intermittent self
      catheterization through a continent catheterizable channel in children with
      bladder dysfunction and outlet obstruction. The active role of pediatric
      urologists in the care, teaching and counseling together with free care to all
      are the reasons for acceptance and compliance.

PMID- 18721967
TI  - Extracorporeal shock wave lithotripsy in pediatric patients using a late
      generation portable lithotriptor: experience at Children's Hospital Boston.
AB  - PURPOSE: Kidney stones in children are increasing in incidence. The continued
      evolution of stone treatment modalities, including shock wave lithotripsy, makes
      the assessment of continuous outcomes essential. We describe contemporary shock
      wave lithotripsy outcomes in pediatric patients. MATERIALS AND METHODS: A medical
      record review was performed of all patients younger than 20 years who underwent
      shock wave lithotripsy in 1998 to 2007. Patients were treated using a Dornier
      Compact Delta lithotriptor with ultrasound and fluoroscopic imaging. Subjects
      were defined as stone-free if imaging within 12 months showed no evidence of
      stones with no additional treatment. Patient and treatment factors associated
      with successful outcomes were analyzed. RESULTS: In 101 children a total of 114
      treatment sequences were performed at a total of 150 shock wave lithotripsy
      sessions. Mean patient age was 10.5 years and 53% of the patients were girls.
      Mean stone diameter was 8 mm. Treatment was done for a solitary stone in 76% of
      cases, for 2 stones in 17% and for 3 or more in 7% with a mean shock count of
      2,247. One, 2 and 3 or more treatment sessions were done in 78%, 16% and 6% of
      patients, respectively. The overall stone-free rate was 58.6%. However, the stone
      free rate was only 12.5% after treatment sequences in 20 children with a history
      of anatomical urological conditions or surgery, while the stone-free rate in
      children without urological conditions was 67% (p <0.0001). Another factor
      associated with a decreased stone-free rate was stone size greater than 10 mm
      (25% vs 63%, p = 0.01). Complications included requiring acute reevaluation or
      treatment after 7% of shock wave lithotripsy sessions and 3.4% of patients
      required readmission. CONCLUSIONS: Extracorporeal shock wave lithotripsy is
      effective in many children with urolithiasis and it is well tolerated. However,
      in some children, particularly those with a history of urological surgery or
      congenital genitourinary conditions, success rates are low. These children may be
      best treated with other modalities.

PMID- 18721969
TI  - Health related quality of life in adolescents with abnormal bladder function: an
      assessment using the Child Health and Illness Profile-Adolescent Edition.
AB  - PURPOSE: We studied the impact of abnormal bladder function due to congenital
      urological disorders on health related quality of life in children. A reliable
      patient based method is needed to assess the impact of these conditions in
      children and the interventions used to treat them. MATERIALS AND METHODS:
      Participants 11 to 17 years old with bladder exstrophy-epispadias complex, spina
      bifida or other causes of abnormal bladder function self-administered the Child
      Health and Illness Profile-Adolescent Edition, a generic health related quality
      of life instrument. They also responded to questions about incontinence,
      catheterization status and bother level. Mean scores on the profile were compared
      to population based norms. RESULTS: Mean age of the 50 participants was 14.9
      years, 62% were male and 82% were white. Diagnoses included bladder exstrophy
      epispadias complex in 37 patients, spina bifida in 10 and other in 3. The mean +/
      SD score on the disorders domain of 14.2 +/- 6.3 was significantly worse than
      the population norm of 20. Mean scores on the satisfaction, discomfort,
      resilience, risks and achievement domains were comparable to or better than the
      population based norm of 20. A total of 29 participants reported incontinence and
      31 performed catheterization. CONCLUSIONS: In this study of adolescents with
      congenital causes of abnormal bladder function Child Health and Illness Profile
      Adolescent Edition generic health related quality of life scores were
      significantly worse in the disorders domain but largely comparable to or better
      than those of the general population in other domains. This suggests that the
      profile may discern between adolescents with structural urological disease and
      norms but it may not be sensitive enough to fully detect the impact of the
      condition. Alternatively adolescents may adapt well to the challenges of
      urological disease.

PMID- 18721971
TI  - Long-term followup of dermal grafts for repair of severe penile curvature.
AB  - PURPOSE: There is some reluctance to use dermal grafts for augmenting the tunica
      albuginea to correct severe forms of chordee. The main concern is that by
      violating the integrity of the tunica albuginea venous leakage could presumably
      ensue and result in erectile dysfunction. We present our long-term followup of
      dermal grafts used to correct severe penile curvature associated with hypospadias
      or as an isolated malformation. MATERIALS AND METHODS: A total of 16 patients
      received a single dermal graft harvested from the nonhair bearing inguinal skin
      fold. Patient age was 1 to 19 years (average 7). Of the patients 14 had
      hypospadias, which was scrotal in 12 and perineal in 2, while 2 had congenital
      penile curvature. In the hypospadias group 13 patients underwent primary repair
      and 1 had undergone 2 previously failed repairs with persistent severe curvature.
      Additionally, 5 patients in the hypospadias group had associated penoscrotal
      transposition. Eight patients in the hypospadias group received testosterone
      injections preoperatively. RESULTS: Average followup was 10 years (range 6 to
      15). At the time of the study all patients were postpubertal and 3 had married.
      Evaluation of the results was based on patient interview reporting of penile
      straightness, erectile quality and satisfaction with sexual relations, if
      present. Two of the 3 patients who married reported satisfactory sexual activity
      and 1 had fathered children. The other 13 patients reported rigid erections. Two
      patients had mild residual curvature that would not necessitate any further
      intervention. CONCLUSIONS: Some boys with severe penile curvature, particularly
      those with hypospadias and a borderline size phallus, need a dermal graft rather
      than a plication procedure to correct curvature. Our study suggests that using
      dermal grafts is safe for erectile function.

PMID- 18721972
TI  - Magnetic resonance arteriography/venography is not accurate to structure
      management of the impalpable testis.
AB  - PURPOSE: Recent studies have shown that magnetic resonance
      arteriography/venography is a highly sensitive tool to identify impalpable testes
      in young boys. Due to this and the low risk of cancer in testicular nubbins
      observation has been proposed after the identification of nubbins by magnetic
      resonance arteriography/venography. We prospectively examined the accuracy of
      magnetic resonance imaging and magnetic resonance imaging with magnetic resonance
      arteriography/venography for identifying impalpable testes in a younger cohort of
      patients typically seen at a pediatric institution in the United States.
      MATERIALS AND METHODS: We prospectively studied 26 infants and boys with
      impalpable testes. Conventional magnetic resonance imaging or magnetic resonance
      imaging with magnetic resonance arteriography/venography was performed in all
      patients. All patients subsequently underwent surgical exploration. Surgical and
      radiological findings were then evaluated for concordance. RESULTS: A total of 26
      boys (29 impalpable testes) with a median age of 13 months were evaluated. A
      subset of 14 boys (14 impalpable testes) also underwent magnetic resonance
      arteriography/venography. Standard magnetic resonance imaging correctly
      identified 10 of 12 intra-abdominal testes, 4 of 6 intracanalicular testes, 4 of
      10 testicular nubbins and 0 of 1 scrotal testis. Magnetic resonance
      arteriography/venography correctly identified 4 of 5 intra-abdominal testes, 2 of
      3 intracanalicular testes, 2 of 5 testicular nubbins and 0 of 1 scrotal testis.
      The overall accuracy of magnetic resonance imaging alone and magnetic resonance
      arteriography/venography for identifying a viable testis or testicular nubbin was
      62% and 57%, respectively. The accuracy of magnetic resonance imaging and
      magnetic resonance arteriography/venography for identifying a viable testis was
      74% and 67%, respectively. CONCLUSIONS: Preoperative magnetic resonance imaging
      or magnetic resonance arteriography/venography does not accurately identify or
      localize impalpable testes in the age group typically presenting to pediatric
      urologists. Accuracy at our institution is discrepant with that in previous
      studies. We do not recommend using magnetic resonance imaging or magnetic
      resonance arteriography/venography for the possible observation of vanishing
      testes or nubbins and we recommend surgical exploration in all individuals.

PMID- 18721975
TI  - Construction of a natural looking inverted umbilicus for bladder exstrophy.
AB  - PURPOSE: Most attempts to create an umbilicus in the exstrophy abdomen eventually
      leave the end result of a flat scar rather than an inverted structure. We
      describe a technique that allows the creation of a better looking inverted
      umbilicus. MATERIALS AND METHODS: A total of 19 patients between 5 days and 7
      years old underwent umbilicoplasty. At the apex of the vertical midline wound the
      skin and superficial fascia are elevated off the anterior rectus sheath well
      beyond the top of the skin incision. The skin edge at the most superior apex of
      the wound is sutured to the linea alba, thereby inverting the skin and fixing it
      to the sheath. Two skin flaps based superiorly are cut from the margin of the
      inverted skin. The flaps are then rotated medial and sutured to the linea alba to
      form the base of the new umbilicus. The superficial fascia inferior to the
      umbilicus is opposed and the skin edges are approximated. RESULTS: A total of 18
      patients had bladder exstrophy and 1 had cloacal exstrophy. Of the patients 11
      underwent bladder/cloacal exstrophy closure, 3 underwent epispadias repair, 3
      underwent bladder neck repair, and 2 underwent bladder augmentation and continent
      cutaneous diversion. Mean +/- SD followup was 6 +/- 4 months. The technique
      allowed the creation of an inverted umbilicus in all patients. None experienced
      infection or dehiscence. The cosmetic result obtained was excellent and durable.
      CONCLUSIONS: We recommend the creation of an inverted umbilicus in the exstrophy
      population at bladder closure or later in life if umbilicoplasty is required.

PMID- 18721979
TI  - Further experience with the vascular hitch (laparoscopic transposition of lower
      pole crossing vessels): an alternate treatment for pediatric ureterovascular
      ureteropelvic junction obstruction.
AB  - PURPOSE: Standard treatment for ureterovascular ureteropelvic junction
      obstruction has been dismembered pyeloplasty. We previously reported the
      alternative technique of laparoscopic transposition of lower pole vessels (the
      vascular hitch) in pediatric patients. This report is an update of this select
      group of pediatric patients with intermediate followup. MATERIALS AND METHODS:
      Patients underwent diagnostic renal sonography and (99m)technetium
      mercaptoacetyltriglycine diuretic renography with additional magnetic resonance
      angiography in candidate patients. Radiographic criteria included moderate
      hydronephrosis with no caliceal dilatation and a well preserved cortex, poor
      renal drainage with preserved split function and lower pole crossing vessels.
      Intraoperative criteria included a normal ureter and ureteropelvic junction with
      peristalsis. Postoperatively patients were followed clinically, and with renal
      sonography and (99m)technetium-mercaptoacetyltriglycine renography at 1 and 2
      months, respectively. Success was defined as symptom resolution with radiographic
      improvement in hydronephrosis and drainage with preserved renal function.
      RESULTS: Nine boys and 11 girls 7 to 16 years old (mean age 12.5) underwent
      laparoscopic transposition of crossing vessels, including 3 with da Vinci robot
      assistance. Mean operative time was 90 minutes (range 47 to 140). Median hospital
      stay was 24 hours. No ureteral stents or urethral catheters were placed
      intraoperatively. At a mean followup of 22 months (range 12 to 42) 19 of 20
      patients (95%) had been successfully treated. One patient who had recurrent pain
      underwent successful laparoscopic pyeloplasty. CONCLUSIONS: At intermediate
      followup the laparoscopic vascular hitch procedure has been successful in
      treating patients with ureterovascular ureteropelvic junction obstruction. In
      these select patients this technique offers a feasible and durable alternative to
      standard dismembered pyeloplasty. Ongoing evaluation continues to ensure that the
      promising results endure.

PMID- 18721980
TI  - Hydrocele in the pediatric patient: inguinal or scrotal approach?
AB  - PURPOSE: The recommended approach for repairing hydrocele in children is inguinal
      to address a patent processus vaginalis. Hydrocele repair in adults is performed
      with a scrotal incision. We identified an age above which a significant percent
      of children had noncommunicating hydroceles, justifying a scrotal approach.
      MATERIALS AND METHODS: A retrospective chart review was performed of children
      undergoing hydrocele repair at our institution between 1998 and 2006. Operative
      reports were reviewed by 2 investigators and intraoperative findings were
      recorded for statistical analysis relating age and findings at the time of the
      procedure using logistic regression and ROC analysis. Laterality and recurrence
      rates were also noted. RESULTS: In this retrospective chart review 82.1% of
      hydroceles in children older than 10 years had intraoperative findings consistent
      with noncommunicating hydrocele and 86.4% in children older than 12 years were
      noncommunicating. One hydrocele in the age group older than 12 years was
      communicating and the history was suggestive of communication. Age was
      significantly associated with a patent processus vaginalis (OR 0.783, p <0.0001).
      CONCLUSIONS: It is possible in children older than 12 years to repair hydroceles
      through a scrotal incision unless the clinical history is suggestive of a
      communication. Children younger than 12 years should undergo inguinal exploration
      for hydrocele repair.

PMID- 18721981
TI  - Timing of the presentation of urethrocutaneous fistulas after hypospadias repair
      in pediatric patients.
AB  - PURPOSE: We evaluated the timing of the presentation of urethrocutaneous fistulas
      after hypospadias repair and the development of recurrent urethrocutaneous
      fistulas after prior fistula repair. MATERIALS AND METHODS: We reviewed the
      charts of all patients with urethrocutaneous fistulas following hypospadias
      repair who were seen from 1995 to 2005. Age at hypospadias repair, hypospadias
      level, hypospadias repair type, time when the parent/patient noted the fistula,
      date/type of fistula repair, time when fistula recurrence was noticed, date/type
      of secondary repair and date of last followup were documented. RESULTS: A total
      of 26 patients with urethrocutaneous fistula were seen, of whom 15 had undergone
      at least 1 prior operation elsewhere. Of the patients 58% and 61% with fistulas
      following hypospadias repair and recurrent fistulas following the initial
      fistula, respectively, presented in the immediate postoperative period. Of the
      patients 23% with initial fistulas presented more than 2 years after hypospadias
      repair (up to 17 years later), while only 5.5% with recurrent fistulas presented
      more than 1 year after fistula repair. Age at presentation with initial fistulas
      after hypospadias repair was 0 to 12 months in 5 patients, 12 to 24 in 6, 24 to
      36 in 6, 36 to 48 in 2 and more than 48 in 7. Mean followup was 5.5 months (range
      0 to 69). CONCLUSIONS: While many urethrocutaneous fistulas develop immediately
      following hypospadias repair, almost a quarter present well beyond the typical
      followup of many urologists. These findings suggest that reported rates of
      urethrocutaneous fistula may be underestimated and longer followup may be
      warranted. Late recurrence of urethrocutaneous fistula is rare with 5.2% seen at
      more than 1 year, suggesting that more limited followup may be appropriate in
      these patients.

PMID- 18721982
TI  - In utero treatment for bladder outlet obstruction using robot assisted
      laparoscopic techniques.
AB  - PURPOSE: Bladder outlet obstruction can have devastating consequences. Given the
      poor outcome, intervention in utero has been advocated in an attempt to salvage
      pulmonary and renal function. We evaluated whether laparoscopic decompression of
      the obstructed bladder could be performed efficiently by adapting current robot
      assisted laparoscopic techniques to access the fetus in utero. MATERIALS AND
      METHODS: At 95 days of gestation 20 fetal sheep underwent ligation of the urethra
      and urachus. Two to 5 days later robot assisted laparoscopic vesicostomy was
      performed. Ultrasound of the kidneys and bladder was performed before each
      procedure. At 135 days of gestation the urinary tract was evaluated to assess the
      adequacy of bladder decompression and a patent vesicostomy. RESULTS: After 48
      hours of undergoing ligation all fetuses had bilateral moderate hydronephrosis
      and a markedly distended bladder. In the first 10 fetuses vesicostomy could not
      be completed laparoscopically due to limited visualization. Additional
      modifications in trocar placement and gas infusion allowed vesicostomy to be
      completed laparoscopically in the last 8 fetuses in 2.5 to 4 hours. Urinary tract
      decompression and a patent vesicostomy were observed in all of these fetuses
      postoperatively. CONCLUSIONS: We developed specific modifications in current
      robot assisted laparoscopic techniques and instrumentation to allow the treatment
      of bladder outlet obstruction in utero. This procedure may be performed
      efficiently and it may provide advantages over conventional surgery for fetal
      intervention.

PMID- 18721983
TI  - Single setting bilateral laparoscopic orchiopexy for bilateral intra-abdominal
      testicles.
AB  - PURPOSE: The laparoscopic surgical approach to unilateral intra-abdominal testis
      has replaced the open approach at several large centers. There is considerable
      literature on experience with unilateral intra-abdominal testes but little on the
      management of bilateral intra-abdominal testes. We assessed the feasibility and
      safety of performing single setting bilateral laparoscopic orchiopexy in boys
      with bilateral intra-abdominal testes. MATERIALS AND METHODS: A single surgeon
      experience was reviewed. The surgical technique was similar in all cases and on
      each side, including infra-umbilical access, diagnostic evaluation, peritoneal
      mobilization lateral to the spermatic vessels and inferior to the vas deferens,
      gubernacular transection, and a decision for or against a Fowler-Stephens
      procedure and testis relocation into the scrotum with fixation. Followup
      consisted of physical examination 14 days, 6 months and 1 year postoperatively,
      when testicular position and size were assessed. Intraoperative and postoperative
      complications were noted. RESULTS: Single setting bilateral laparoscopic
      orchiopexy was attempted in a total of 42 testes in 21 boys with a median age of
      9 months (range 7 to 52). It was completed in a total of 36 testes in 18 boys.
      All procedures were performed on an outpatient basis. Of the 42 testes orchiopexy
      was performed in 4 with Fowler-Stephens ligation, including at a 1 and 2-stage
      procedure in 2 each. Although the latter 2 cases account for 2 of the 3 not
      completed at a single setting, excellent outcomes were achieved in these cases at
      the second setting, yielding bilateral intrascrotal testes in each. A third boy
      required a subsequent open procedure for relocation of a testis from an inferior
      pubic/superior scrotal position to a more dependent portion of the scrotum.
      Testicular position after laparoscopy was the mid lower scrotum in 38 cases,
      upper scrotum in 3 and inferior pubic/superior scrotal in 1. Atrophy was noted in
      2 of the 42 testes (19 of 21 boys) at 6-month followup, including in 1 boy who
      underwent a 1-stage Fowler-Stephens procedure and 1 who underwent nonFowler
      Stephens orchiopexy. Of the 21 boys 16 required only 1 surgery to achieve viable
      intrascrotal testes at 1-year followup. Of the 21 boys 19 (91%) ultimately
      achieved bilateral viable intrascrotal testes. There was no correlation between
      patient age and the likelihood of success or failure. No patient experienced any
      complications or hospital admissions. CONCLUSIONS: In boys with bilateral intra
      abdominal testes single setting bilateral laparoscopic orchiopexy can be
      performed safely on an outpatient basis with a high degree of success. Most boys
      undergo a single surgery with the testes relocated to a satisfactory intrascrotal
      position without atrophy.

PMID- 18721985
TI  - Complete excision or marsupialization of ureteroceles: does choice of surgical
      approach affect outcome?
AB  - PURPOSE: Two accepted open surgical techniques exist for lower urinary tract
      reconstruction for ureteroceles, that is complete excision/enucleation and
      marsupialization/partial excision. To our knowledge it is currently unknown
      whether 1 method offers better clinical outcomes. We sought to answer this
      question. MATERIALS AND METHODS: We retrospectively reviewed the records of
      patients who underwent open surgical repair for ureterocele at 3 academic
      institutions. The 2 groups (complete excision vs marsupialization) were compared
      for each clinical outcome, including ongoing vesicoureteral reflux, new bladder
      diverticulum, hydronephrosis, continence, urinary tract infection and voiding
      dysfunction. Each clinical outcome was analyzed for independence from the
      surgical method. RESULTS: A total of 33 cases of complete excision and 24 of
      marsupialization were collected. The excision and marsupialization groups were
      similar with respect to patient age at surgery, gender and average followup (55
      and 38 months, respectively). Most ureteroceles were unilateral and part of a
      duplicated system. Approximately half were intravesical and vesicoureteral reflux
      was the primary indication for surgery. In the excision group 82% of ureteroceles
      were previously punctured but only 50% were punctured in the marsupialization
      group (p = 0.09). Postoperatively the groups did not differ significantly in
      terms of ongoing vesicoureteral reflux (13% and 14%), bladder diverticulum (3%
      and 9%), continence (100% and 95%), urinary tract infection (43% and 46%) or
      voiding dysfunction (24% and 25%, respectively). They varied significantly in
      terms of improved or stable hydronephrosis (70% vs 91%, p = 0.05). CONCLUSIONS:
      When performing lower urinary tract reconstruction for ureterocele, this study
      demonstrates that the choice of complete excision vs marsupialization/partial
      excision does not appear to differentially affect clinical outcomes.

PMID- 18721990
TI  - Superiority of the VQZ over the tubularized skin flap and the umbilicus for
      continent abdominal stoma in children.
AB  - PURPOSE: Stricture prevention, avoiding exposed mucosa and cosmesis are important
      considerations when constructing continent abdominal stomas. We analyzed our
      results of continent abdominal stomas using the umbilicus and 2 types of lower
      abdominal stomas, that is the V-quadrilateral-Z technique and the tubular skin
      flap. MATERIALS AND METHODS: Patient charts were reviewed retrospectively. All
      patients with a continent abdominal stoma were included in our study. Patients
      were divided into 3 groups according to type of stoma, including umbilicus,
      tubular skin flap and V-quadrilateral-Z. The groups were compared regarding
      demographics, etiology, success, complications and the need for revision.
      RESULTS: A total of 40 incontinent patients were included in our study. All
      underwent Mitrofanoff urinary diversion (37) and/or Malone antegrade continence
      enema construction (13) between 1993 and 2007. The umbilicus was used for 31
      conduits, the V-quadrilateral-Z was used for 8 and the tubular skin flap was used
      for 11. Patient age and gender, and the etiology of incontinence were similar in
      the 3 groups. All patients achieved good cosmesis with a hidden bowel mucosa. In
      the V-quadrilateral-Z group no patient had stomal stenosis. Five patients (45%)
      in the tubular skin flap group required dilation or revision for obstruction or
      stenosis, which was successful in 4. Eight umbilical conduits (25%) had to be
      dilated or revised due to stomal stenosis (6) and conduit obstruction (2).
      CONCLUSIONS: Initial results with the V-quadrilateral-Z flap show its superiority
      over the tubular skin flap and the umbilicus for stomal construction in patients
      with a Mitrofanoff or Malone antegrade continence enema conduit.

PMID- 18721992
TI  - The UK public health system: change and constancy.
AB  - The public health system in the UK has evolved from medical officer posts rooted
      in the era of sanitary reform to a modern service embedded within the National
      Health Service. The challenge for today's public health function is to retain a
      broad-based philosophy encompassing population programmes addressing health
      inequalities, whilst also delivering the personalized approach to supporting
      lifestyle change which is being demanded increasingly.

PMID- 18721994
TI  - [Piezosurgery for genioglossal advancement in treatment of obstructive sleep
      apnea syndrome].
AB  - The tongue is a frequent cause of upper airway obstruction in obstructive sleep
      apnea syndrome. The genioglossi muscles are the front-most muscles of the tongue,
      attached to the geniotubercle on the inner cortical of the mandibular symphisis.
      The collapsibility of the tongue can be managed with genioglossus advancement.
      Piezo surgery can decrease the risk of apical dental lesion. The perfect depth
      control during osteotomy and absence of soft tissue lesion considerably limit the
      risks of oral floor lesion.

PMID- 18721993
TI  - A physiologically based pharmacokinetic model linking plasma protein binding
      interactions with drug disposition.
AB  - Combination drug therapy increases the chance for an adverse drug reactions due
      to drug-drug interactions. Altered disposition for sulfamethazine (SMZ) when
      concurrently administered with flunixin meglumine (FLU) in swine could lead to
      increased tissue residues. There is a need for a pharmacokinetic modeling
      technique that can predict the consequences of possible drug interactions. A
      physiologically based pharmacokinetic model was developed that links plasma
      protein binding interactions to drug disposition for SMZ and FLU in swine. The
      model predicted a sustained decrease in total drug and a temporary increase in
      free drug concentration. An in vivo study confirmed the presence of a drug
      interaction. Neither the model nor the in vivo study revealed clinically
      significant changes that alter tissue disposition. This novel linkage approach
      has use in the prediction of the clinical impact of plasma protein binding
      interactions. Ultimately it could be used in the design of dosing regimens and in
      the protection of the food supply through prediction and minimization of tissue
      residues.

PMID- 18721995
TI  - Homologous recombination evidence in human and swine influenza A viruses.
AB  - Dynamic gene mutation and the reassortment of genes have been considered as the
      key factors responsible for influenza A virus virulence and host tropism change.
      This study reports several significant evidence demonstrating that homologous
      recombination also takes place between influenza A viruses in human and swine
      lineages. Moreover, in a mosaic descended from swine H1N1 subtype and human H2N2,
      we found that its minor putative parent might be a derivative from the human cold
      adapted vaccine lineage, which suggests that live vaccine is capable of playing a
      role in genetic change of influenza A virus via recombination with circulating
      viruses. These results would be important for knowing the molecular mechanism of
      mammal influenza A virus heredity and evolution.

PMID- 18721996
TI  - Nitrate attenuation in groundwater: a review of biogeochemical controlling
      processes.
AB  - Biogeochemical processes controlling nitrate attenuation in aquifers are
      critically reviewed. An understanding of the fate of nitrate in groundwater is
      vital for managing risks associated with nitrate pollution, and to safeguard
      groundwater supplies and groundwater-dependent surface waters. Denitrification is
      focused upon as the dominant nitrate attenuation process in groundwater. As
      denitrifying bacteria are essentially ubiquitous in the subsurface, the critical
      limiting factors are oxygen and electron donor concentration and availability.
      Variability in other environmental conditions such as nitrate concentration,
      nutrient availability, pH, temperature, presence of toxins and microbial
      acclimation appears to be less important, exerting only secondary influences on
      denitrification rates. Other nitrate depletion mechanisms such as dissimilatory
      nitrate reduction to ammonium and assimilation of nitrate into microbial biomass
      are unlikely to be important in most subsurface settings relative to
      denitrification. Further research is recommended to improve current understanding
      on the influence of organic carbon, sulphur and iron electron donors, physical
      restrictions on microbial activity in dual porosity aquifers, influences of
      environmental condition (e.g. pH in poorly buffered environments and salinity in
      coastal or salinized soil settings), co-contaminant influences (particularly the
      contrasting inhibitory and electron donor influences of pesticides) and improved
      quantification of denitrification rates in the laboratory and field.

PMID- 18721997
TI  - The pathway of dechlorination of PCB congener by a photochemical chain process in
      2-propanol: the role of medium and quenching.
AB  - As part of a program aimed at developing a field process for cleanup of PCB
      contaminated soils using photochemistry in basic 2-propanol, additional details
      of the dechlorination pathway are presented. The mechanism involves a chain
      reaction with both homolytic photochemical C-Cl bond fission and electron
      transfer steps producing PCB anion radicals. Kinetics of dechlorination of
      various congeners show patterns of relative rates associated with the basic 2
      propanol medium that are not found in other media because both electron transfer
      and photochemical homolysis steps determine overall rates of dechlorination and
      govern the pathways and relative concentrations of intermediates. The electron
      transfer steps display opposite structure-reactivity correlations to the photo
      homolysis, C-Cl bond fission steps. Oxygen quenching is shown to differentially
      affect both types of steps. In contrast to the suggestion that inter system
      crossing can be highly efficient with reaction originating from a PCB triplet,
      oxygen quenching data suggest that a significant minimum of the quantum yield is
      non-quenchable, presumably because of a reaction path from the PCB singlet. This
      may help to explain why exclusion of air is not entirely necessary in practice.

PMID- 18721998
TI  - Suggested guidelines for invasive sampling of hominid remains.

PMID- 18722000
TI  - Perchlorate production by ozone oxidation of chloride in aqueous and dry systems.
AB  - Overwhelming evidence now exists that perchlorate is produced through natural
      processes and can be ubiquitously found at environmentally relevant
      concentrations in arid and semi-arid locations. A number of potential production
      mechanisms have been hypothesized and ClO(4)(-) production by ozone oxidation of
      surface bound Cl(-) was demonstrated. However, no information concerning the
      impact of concentration, final reaction products distribution, impact of reaction
      phase, or oxidation of important oxychlorine intermediates has been reported.
      Using IC-MS-MS analysis and replicate oxidation experiments, we show that
      exposing aqueous solutions or Cl(-) coated sand or glass surfaces to O(3) (0.96%)
      generated ClO(4)(-) with molar yields of 0.007 and 0.01% for aqueous Cl(-)
      solutions and 0.025 and 0.42% for Cl(-) coated sand and glass, respectively.
      Aqueous solutions of Cl(-) produced less ClO(4)(-) than Cl(-) coated sand or
      glass as well as a higher ratio of ClO(3)(-) to ClO(4)(-). Reduction of the
      initial Cl(-) mass resulted in substantially higher molar yields of ClO(4)(-) and
      ClO(3)(-). In addition, alkaline absorbers that captured gaseous products
      contained substantial quantities of Cl(-), ClO(3)(-), and ClO(4)(-). Solutions of
      possible oxychlorine intermediates (OCl(-) and ClO(3)(-)) exposed to O(3)
      produced only scant amounts of ClO(4)(-) while a ClO(2)(-) solution exposed to
      O(3) produced substantial molar yields of ClO(4)(-) (4% molar yield). Scanning
      electron microscopy coupled with energy energy-dispersive X-ray analysis
      demonstrated a significant loss of Cl(-) and an increase in oxygen on the Cl(-)
      coated silica sand exposed to O(3). While the experimental conditions are not
      reflective of natural conditions this work clearly demonstrates the relative
      potential of Cl(-) precursors in perchlorate production and the likely importance
      of dry aerosol oxidation over solution phase reactions. It also suggests that
      ClO(2)(-) may be a key intermediate while ClO(3)(-) and OCl(-) are unlikely to
      play a significant role.

PMID- 18721999
TI  - Oxygen isotope fractionation between human phosphate and water revisited.
AB  - The oxygen isotope composition of human phosphatic tissues (delta18OP) has great
      potential for reconstructing climate and population migration, but this technique
      has not been applied to early human evolution. To facilitate this application we
      analyzed delta18OP values of modern human teeth collected at 12 sites located at
      latitudes ranging from 4 degrees N to 70 degrees N together with the
      corresponding oxygen composition of tap waters (delta18OW) from these areas. In
      addition, the delta18O of some raw and boiled foods were determined and simple
      mass balance calculations were performed to investigate the impact of solid food
      consumption on the oxygen isotope composition of the total ingested water
      (drinking water+solid food water). The results, along with those from three,
      smaller published data sets, can be considered as random estimates of a unique
      delta18OW/delta18OP linear relationship: delta18OW=1.54(+/-0.09)xdelta18OP
      33.72(+/-1.51)(R2=0.87: p [H0:R2=0]=2x10(-19)). The delta18O of cooked food is
      higher than that of the drinking water. As a consequence, in a modern diet the
      delta18O of ingested water is +1.05 to 1.2 per thousand higher than that of
      drinking water in the area. In meat-dominated and cereal-free diets, which may
      have been the diets of some of our early ancestors, the shift is a little higher
      and the application of the regression equation would slightly overestimate
      delta18OW in these cases.

PMID- 18722001
TI  - Application of bioemulsifiers in soil oil bioremediation processes. Future
      prospects.
AB  - Biodegradation is one of the primary mechanisms for elimination of petroleum and
      other hydrocarbon pollutants from the environment. It is considered an
      environmentally acceptable way of eliminating oils and fuel because the majority
      of hydrocarbons in crude oils and refined products are biodegradable. Petroleum
      hydrocarbon compounds bind to soil components and are difficult to remove and
      degrade. Bioemulsifiers can emulsify hydrocarbons enhancing their water
      solubility and increasing the displacement of oily substances from soil
      particles. For these reasons, inclusion of bioemulsifiers in a bioremediation
      treatment of a hydrocarbon polluted environment could be really advantageous.
      There is a useful diversity of bioemulsifiers due to the wide variety of producer
      microorganisms. Also their chemical compositions and functional properties can be
      strongly influenced by environmental conditions. The effectiveness of the
      bioemulsifiers as biostimulating agent in oil bioremediation processes has been
      demonstrated by several authors in different experimental assays. For example,
      they have shown to be really efficient in combination with other products
      frequently used in oil bioremediation such as they are inorganic fertilizer (NPK)
      and oleophilic fertilizer (i.e. S200C). On the other hand, the bioemulsifiers
      have shown to be more efficient in the treatment of soil with high percentage of
      clay. Finally, it has been proved their efficacy in other biotechnological
      processes such as in situ treatment and biopiles. This paper reviews literature
      concerning the application of bioemulsifiers in the bioremediation of soil
      polluted with hydrocarbons, and summarizes aspects of the current knowledge about
      their industrial application in bioremediation processes.

PMID- 18722003
TI  - Pre-clinical studies of plasmin: superior benefit-to-risk ratio of plasmin
      compared to tissue plasminogen activator.
AB  - Currently-used thrombolytic agents are plasminogen activators (PA). While
      effective for treating thrombotic disease, PA use is associated with unavoidable
      hemorrhagic complications in susceptible individuals. Thus, there is an urgent
      need for new agents or approaches that provide greater hemostatic safety without
      sacrificing thrombolytic efficacy. Evidence now strongly indicates that 'direct
      acting' thrombolytics, which do not require conversion of the precursor
      plasminogen to the active form plasmin, offer such a potential. The biochemical
      properties of plasmin provide a theoretical foundation for safe and effective
      therapy, based on thrombolytic efficacy upon local catheter delivery of agent and
      neutralization of circulating agent by its inhibitor (alpha-2 antiplasmin) to
      prevent bleeding complications. In vitro and animal studies support these
      predictions. In comparison with tissue-plasminogen activator (t-PA), plasmin
      shows a distinct benefit-to-risk advantage. First, plasmin is equally effective
      as t-PA in thrombolysis and may be superior for treating thrombi in totally
      occluded vessels. Second, whereas t-PA causes bleeding from vascular trauma sites
      in animals when infused at dosages used for thrombolysis (0.5-1 mg/kg), plasmin
      exhibits safety at therapeutic dosages. In fact, plasmin can be used at several
      fold higher concentrations than is needed for thrombolysis, thereby providing a
      significant safety margin that is not attainable for t-PA or other PAs. Phase I
      trials with plasmin in hemodialysis graft occlusion and peripheral arterial
      occlusion have thus far confirmed the hemostatic safety of plasmin.

PMID- 18722004
TI  - Reducing ovarian cancer mortality through screening: Is it possible, and can we
      afford it?
AB  - OBJECTIVE: Ovarian cancer is a leading cause of cancer-related deaths among
      women. Given the low prevalence of this disease, the effectiveness of screening
      strategies has not been established. We wished to estimate the clinical impact
      and cost-effectiveness of potential screening strategies for ovarian cancer using
      population-specific data. METHODS: A Markov state transition model to simulate
      the natural history of ovarian cancer in a cohort of women age 20 to 100. Age
      specific incidence and mortality rates were obtained from SEER. Base-case
      characteristics of a potential screening test were sensitivity 85%, specificity
      95%, and cost $50. Outcome measures were mortality reduction, lifetime number of
      false positive screening tests, positive predictive value, years of life saved
      (YLS), lifetime costs in US dollars, and incremental cost-effectiveness ratios
      (ICER, in cost/YLS). RESULTS: Model-predicted lifetime risk of ovarian cancer
      (1.38%), lifetime risk of death from ovarian cancer (0.95%), and stage
      distribution (stage I-19%; stage II-7%; stage III, IV, or unstaged - 74%) closely
      approximated SEER data. Annual screening resulted in 43% reduction in ovarian
      cancer mortality, with ICER of $73,469/YLS (base case) and $36,025/YLS (high-risk
      population) compared to no screening. In the base case, the average lifetime
      number of false positive tests is 1.06. Cost-effectiveness of screening is most
      sensitive to test frequency, specificity and cost. CONCLUSIONS: Annual screening
      for ovarian cancer has the potential to be cost effective, particularly in high
      risk populations. Clinically acceptable positive predictive values are achieved
      if specificity exceeds 99%. Mortality reduction above 50% may not be achievable
      without screening intervals less than 12 months.

PMID- 18722005
TI  - Detection of micrometastases in pelvic lymph nodes in patients with carcinoma of
      the cervix uteri using step sectioning: Frequency, topographic distribution and
      prognostic impact.
AB  - OBJECTIVES: Limited information exist about the frequency of micrometastases,
      their topographic distribution and prognostic impact in patients with cervical
      carcinoma (CX). METHODS: Lymph nodes of patients with surgically treated CX, FIGO
      IB to IIB, with pelvic lymph node involvement, were re-examined regarding the
      size of metastatic deposits, their topographic distribution within the pelvis.
      Lymph node status (pN0 vs. pN1mic=metastasis<0.2 cm vs. pN1=metastasis>0.2 cm)
      was correlated to recurrence free (RFS) and overall survival (OS). RESULTS: 31.4%
      of all patients (281/894) represented pelvic lymph node involvement. 22.2.% of
      the node positive ones showed micrometastases (pN1mic). Most commonly, obturator
      and internal nodes were affected by pN1mic, without any side differences.
      Patients with macrometastases (pN1) and micrometastases (pN1mic) represented
      significant reduced RFS-rate at 5-years (62% [95% CI: 54.2 to 69.8] for pN1 and
      68.9% [95% CI: 55.5 to 82.4] for pN1mic) when compared to patients without
      metastatic disease (91.4% [95% CI: 89.0 to 93.8]; p<0.001) The 5-years OS-rate
      was decreased in patients with metastatic disease (pN0: 86.6% [95% CI: 83.7 to
      89.5], pN1mic: 63.8% [95% CI: 50.9 to 76.7], pN1: 48.2% [95% CI: 40.4 to 56.0];
      p<0.0001). These differences persisted in detailed analysis within these
      subgroups. In multivariate analysis, tumor stage, pelvic lymph node involvement
      and micrometastases were independent prognostic factors. CONCLUSIONS: A
      remarkable number of patients with CX show micrometastases within pelvic nodes.
      Micrometastatic disease represents an independent prognostic factor. So, all
      patients with pelvic lymph node involvement, including micrometastatic deposits,
      might be candidates for adjuvant treatment.

PMID- 18722006
TI  - Global sequencing of proteolytic cleavage sites in apoptosis by specific labeling
      of protein N termini.
AB  - The nearly 600 proteases in the human genome regulate a diversity of biological
      processes, including programmed cell death. Comprehensive characterization of
      protease signaling in complex biological samples is limited by available
      proteomic methods. We have developed a general approach for global identification
      of proteolytic cleavage sites using an engineered enzyme to selectively
      biotinylate free protein N termini for positive enrichment of corresponding N
      terminal peptides. Using this method to study apoptosis, we have sequenced 333
      caspase-like cleavage sites distributed among 292 protein substrates. These sites
      are generally not predicted by in vitro caspase substrate specificity but can be
      used to predict other physiological caspase cleavage sites. Structural
      bioinformatic studies show that caspase cleavage sites often appear in surface
      accessible loops and even occasionally in helical regions. Strikingly, we also
      find that a disproportionate number of caspase substrates physically interact,
      suggesting that these dimeric proteases target protein complexes and networks to
      elicit apoptosis.

PMID- 18722007
TI  - Putative sex differences in verbal abilities and language cortex: a critical
      review.
AB  - This review brings together evidence from a diverse field of methods for
      investigating sex differences in language processing. Differences are found in
      certain language-related deficits, such as stuttering, dyslexia, autism and
      schizophrenia. Common to these is that language problems may follow from, rather
      than cause the deficit. Large studies have been conducted on sex differences in
      verbal abilities within the normal population, and a careful reading of the
      results suggests that differences in language proficiency do not exist. Early
      differences in language acquisition show a slight advantage for girls, but this
      gradually disappears. A difference in language lateralization of brain structure
      and function in adults has also been suggested, perhaps following size
      differences in the corpus callosum. Neither of these claims is substantiated by
      evidence. In addition, overall results from studies on regional grey matter
      distribution using voxel-based morphometry, indicate no consistent differences
      between males and females in language-related cortical regions. Language function
      in Wada tests, aphasia, and in normal ageing also fails to show sex
      differentiation.

PMID- 18722008
TI  - Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense
      mutations: a prospective phase II trial.
AB  - BACKGROUND: In about 10% of patients worldwide and more than 50% of patients in
      Israel, cystic fibrosis results from nonsense mutations (premature stop codons)
      in the messenger RNA (mRNA) for the cystic fibrosis transmembrane conductance
      regulator (CFTR). PTC124 is an orally bioavailable small molecule that is
      designed to induce ribosomes to selectively read through premature stop codons
      during mRNA translation, to produce functional CFTR. METHODS: This phase II
      prospective trial recruited adults with cystic fibrosis who had at least one
      nonsense mutation in the CFTR gene. Patients were assessed in two 28-day cycles.
      During the first cycle, patients received PTC124 at 16 mg/kg per day in three
      doses every day for 14 days, followed by 14 days without treatment; in the second
      cycle, patients received 40 mg/kg of PTC124 in three doses every day for 14 days,
      followed by 14 days without treatment. The primary outcome had three components:
      change in CFTR-mediated total chloride transport; proportion of patients who
      responded to treatment; and normalisation of chloride transport, as assessed by
      transepithelial nasal potential difference (PD) at baseline, at the end of each
      14-day treatment course, and after 14 days without treatment. The trial was
      registered with who.int/ictrp, and with clinicaltrials.gov, number NCT00237380.
      FINDINGS: Transepithelial nasal PD was evaluated in 23 patients in the first
      cycle and in 21 patients in the second cycle. Mean total chloride transport
      increased in the first treatment phase, with a change of -7.1 (SD 7.0) mV
      (p<0.0001), and in the second, with a change of -3.7 (SD 7.3) mV (p=0.032). We
      recorded a response in total chloride transport (defined as a change in nasal PD
      of -5 mV or more) in 16 of the 23 patients in the first cycle's treatment phase
      (p<0.0001) and in eight of the 21 patients in the second cycle (p<0.0001). Total
      chloride transport entered the normal range for 13 of 23 patients in the first
      cycle's treatment phase (p=0.0003) and for nine of 21 in the second cycle
      (p=0.02). Two patients given PTC124 had constipation without intestinal
      obstruction, and four had mild dysuria. No drug-related serious adverse events
      were recorded. INTERPRETATION: In patients with cystic fibrosis who have a
      premature stop codon in the CFTR gene, oral administration of PTC124 to suppress
      nonsense mutations reduces the epithelial electrophysiological abnormalities
      caused by CFTR dysfunction.

PMID- 18722009
TI  - Ignoring the nonsense: a phase II trial in cystic fibrosis.

PMID- 18722010
TI  - Blood compatibility of surfaces with superlow protein adsorption.
AB  - In this work, five self-assembled monolayers (SAMs) and three polymeric brushes
      with very low fibrinogen adsorption were prepared. The five SAMs are
      oligo(ethylene glycol) (OEG), phosphorylcholine (PC), oligo(phosphorylcholine)
      (OPC), and two mixed positively and negatively charged SAMs of SO(3)(
      )/N(+)(CH(3))(3) (SA/TMA) and COO(-)/N(+)(CH(3))(3) (CA/TMA). Three polymer
      brushes were prepared on gold surfaces via surface-initiated atom transfer
      radical polymerization (ATRP) using three monomers, sulfobetaine methacrylate
      (SBMA), carboxybetaine methacrylate (CBMA), and oligo(ethylene glycol) methyl
      ether methacrylate (OEGMA). Surface plasmon resonance (SPR) measurements show
      that although all of these surfaces are "nonfouling" to fibrinogen adsorption
      from buffer solution, their protein adsorption from undiluted human blood plasma
      varies widely. Polymer brushes exhibit much lower protein adsorption from plasma
      than any of the five SAMs tested. However, platelet adhesion measurements on
      plasma-preadsorbed surfaces show that all of these surfaces have very low
      platelet adhesion. Clotting time measurements using recalcified platelet poor
      plasma (PPP) incubation with the eight types of surfaces show that they do not
      shorten clotting times. Linear polymers of polySBMA and polyCBMA with similar
      molecular weights were also synthesized and characterized. In the presence of
      polyCBMA linear polymers, the clotting time of PPP was prolonged and increased
      with the concentration of the polymer, while no anticoagulant activity was
      observed for the polySBMA or PEG polymers. The unique anticoagulant activity of
      polyCBMA, as well as its high plasma protein adsorption resistance, makes
      polyCBMA a candidate for blood-contacting applications.

PMID- 18722011
TI  - Effects of imatinib mesylate on normal bone marrow cells from chronic myeloid
      leukemia patients in complete cytogenetic response.
AB  - Information on the effects of imatinib mesylate (IM) on the non-clonal bone
      marrow (BM) cell compartment is scanty. We have analyzed the gene expression
      profile of BM hematopoietic cells after IM therapy in 20 patients with chronic
      myeloid leukaemia (CML) in complete cytogenetic response (CCyR) and compared it
      with that of normal volunteer donors by oligonucleotide microarrays. In CCyR CML
      samples, IM induces a decrease in proliferation as well as increase in apoptosis
      and ubiquitination in residual non-clonal BM cells. In addition, IM diminishes
      cell-to-cell adhesion and downregulates the expression of the erythropoietin
      (EPO) receptor gene. The latter was confirmed by RT-PCR.

PMID- 18722012
TI  - Sequential toxicity identification evaluation (TIE) for characterizing toxicity
      of Venice Lagoon sediments: comparison of two different approaches.
AB  - A toxicity identification evaluation phase-I (TIE-1) procedure was carried out on
      five pore water samples extracted from sediments of the Venice Lagoon previously
      investigated to assess both chemical contamination and toxic effects on the
      biota. Two different sequential TIE procedures were tested. A first sequence (TIE
      1) provided for adding Na2S2O3, adding Na-EDTA, filtering, elution through a C18
      SPE column and removing ammonia using the macroalgae Ulva rigida Agardh 1823,
      while a second procedure (TIE-2) was set up using U. rigida treatment for ammonia
      removal as first step, keeping unchanged the sequence of the other manipulations.
      Two different exposure time to the macroalgae were tested (3-h and 15-h). Sperm
      cell toxicity test with the echinoid Paracentrotus lividus and embryotoxicity
      tests with the bivalves Mytilus galloprovincialis and Crassostrea gigas were
      performed on pore-water samples to assess the effect of the sequential treatments
      on the overall toxicity. The results confirmed that ammonia contribution to
      toxicity is strong in most of the samples and that metals, specially Cu, are of
      concern at least in three sites. The TIE-2 procedure provided more reliable
      results for the samples characterized by high ammonia contribution to the overall
      toxicity, whereas the results of TIE-1 and TIE-2 were equivalent for the samples
      where ammonia contribution was not prevailing. Chemical analyses and test results
      showed that a 3-h U. rigida exposure is suitable to remove ammonia toxicity
      minimizing potential metal up-take.

PMID- 18722013
TI  - Comparison of fate and ecological effects of the herbicide linuron in freshwater
      model ecosystems between tropical and temperate regions.
AB  - This paper compares the fate and effects of linuron in an outdoor plankton
      dominated microcosm study carried out in Thailand with those reported in
      temperate model ecosystem studies evaluating linuron and other photosynthesis
      inhibiting herbicides. Lower linuron concentrations disappeared slightly faster
      from the water compartment compared to temperate conditions, which appears to be
      related with the experimental design rather than differences in climatic
      conditions. Sensitivity of primary producers and zooplankton were similar for the
      climatic regions, whereas effects on ecosystem functioning were less pronounced
      in tropical microcosms. Recovery potential of affected endpoints appears higher
      for tropical ecosystems compared to their temperate counterparts. These findings
      support the use of toxicity data generated in temperate countries in the tropics.
      Recommendations for the methodology of tropical model ecosystem experiments are
      discussed.

PMID- 18722014
TI  - Sturge-Weber syndrome with cerebellar involvement.
AB  - Sturge-Weber syndrome is a rare neurocutaneous disorder that typically presents
      with angiomas involving the face, ocular choroid and ipsilateral supratentorial
      leptomeninges. Posterior fossa involvement is extremely rare. We present two
      patients with simultaneous supra- and infratentorial involvement. Magnetic
      resonance imaging (MRI) and digital subtracted angiography (DSA) findings are
      discussed.

PMID- 18722015
TI  - In vitro affinity maturation of human GM-CSF antibodies by targeted CDR
      diversification.
AB  - The mammalian immune system applies somatic hypermutation to select for
      antibodies with improved dissociation rates in vivo up to an intrinsic limit,
      previously termed as affinity ceiling. However, for certain therapeutic
      applications it may be desirable to further improve antibody affinities beyond
      that limit. In this study the selection of antibodies specific for the pro
      inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF)
      from the HuCAL GOLD human antibody library is described. In order to increase
      affinity and also functional activity, in vitro affinity maturation of a pool of
      lead Fab candidates was carried out. CDR-L3 and parallel CDR-H2 diversification
      using trinucleotide consensus cassettes were followed by the combination of
      optimized CDR-L3 and CDR-H2 leading to a 5000-fold improved affinity finally
      reaching a K(D) of 400 fM. Cytokine neutralizing potential of MOR04357 was
      evaluated in a TF-1 proliferation assay. Along with affinity optimization a 2000
      fold increase in potency was observed compared to the parental antibody. Due to
      species cross-reactivity MOR04357 also blocks rat GM-CSF induced proliferation of
      FDCP-1 cells. Receptor inhibition studies showed that MOR04357 prevents the
      interaction of GM-CSF with the GM-CSF receptor alpha chain. As a consequence this
      leads to a blockade in signal transduction as measured by abolished STAT5
      phosphorylation in the presence of GM-CSF and antibody. Due to its pro
      inflammatory role GM-CSF has been implicated in the pathophysiology of
      inflammatory diseases like rheumatoid arthritis or asthma. Based on the mode of
      action described herein MOR04357 shows favourable antibody features as a
      potential drug candidate.

PMID- 18722016
TI  - SATB1 is required for CD8 coreceptor reversal.
AB  - Intrathymic signals induce the differentiation of immature CD4(+)CD8(+) double
      positive (DP) thymocytes into mature CD4(+) or CD8(+) single positive (SP) T
      cells. The transcriptional mechanism by which CD8 lineage is determined is not
      fully understood. The best evidence, which favors the kinetic
      signaling/coreceptor reversal model, indicates that signaled DP thymocytes
      terminate CD8 transcription prior to their subsequent re-initiation of CD8
      transcription and ultimate differentiation into CD8SP T cells. We and others have
      shown that CD8 lineage commitment is severely perturbed in mice in which
      expression of the transcription factor SATB1 is either conventionally knocked out
      or T cell-specifically knocked down. Here, we demonstrate that, as with normal
      thymocytes, cultured SATB1-deficient DP thymocytes inactivate CD8 coreceptor
      transcription following receipt of signals (PMA plus ionomycin) that mimic TCR
      mediated positive selection. However, this terminated CD8 transcription is not re
      initiated by signals (IL-7) conducive to CD8 differentiation in SATB1-deficient
      DP. We show that SATB1 specifically binds to a cis-regulatory element within the
      CD8 enhancer (E8(III)) known to be required for coreceptor reversal. A
      requirement in CD8 coreceptor reversal identifies SATB1 as an essential trans
      regulator of CD8 lineage fate, whose action may be mediated via recruitment to
      the E8(III) DP enhancer.

PMID- 18722017
TI  - Fibroblastic reticular cells of the peripheral lymphoid organs: unique features
      of a ubiquitous cell type.
AB  - The highly ordered structure in peripheral lymphoid tissues is maintained by
      continuous interactions between their hemopoietic and stromal components. The
      main reticular cell type, fibroblastic reticular cells (FRCs) emerged as a
      considerably heterogeneous group of the stroma. These cells have diverse roles
      beyond architectural scaffolding. Their functions include the formation of nests
      for recirculating lymphocytes with subset-preference and a dynamic filtration
      system for facilitating encounter between antigen, antigen-presenting cells and
      antigen-receptor bearing cells. FRCs are influenced by lymphocyte-derived
      morphogenic signals and factors necessary for lymphoid tissue formation and
      lymphocyte homeostasis. Moreover, FRCs may also interact with other stromal
      elements during both lymphoid organ development and immune responses. FRCs are
      profoundly affected by pathogens, which may limit the lymphoid cells' capacity to
      establish efficient protection. This review focuses on the ontogenic, phenotypic
      and functional complexities of FRCs and their role in the stromal rearrangement
      of lymphoid tissues.

PMID- 18722018
TI  - Human visceral leishmaniasis expresses Th1 pattern in situ liver lesions.
AB  - The architectural and infiltrate pattern of liver human visceral leishmaniasis
      (HVL) have been systematically classified as typical, fibrogenic or nodular.
      Despite this histopathological classification, the immune response based on
      cytokines and cellular phenotypes have never been performed. The aim of this
      study was to determine the immunophenotypic pattern and cytokine profile of the
      nodular involvement of the liver in HVL. We evaluated nine cases of the nodular
      form of HVL. In situ immune response was studied through cytokine analysis and
      immunohistochemical study for phenotype markers: IL-1, IL-4, IL-10, TNF-alpha,
      IFN-gamma, CD4+ T cells, CD8+ T cells, CD20, CD68, CD57 and macrophage activation
      was determined by evaluation of iNOS activity. HVL seems to be related to a
      better immune response. Amastigotes were rarely found on liver sections.
      Leishmania antigen expression was also rare and located in the inflammatory
      nodules. The lower expression of IL-4 and IL-10, moderate expression of TNF-alpha
      and IFN-gamma demonstrate a panorama of Th1 phenotype. The increased expression
      of NK cells could help in sustaining this model of response. This pattern of
      immune response is probably responsible for improvement in the parasite's
      clearance from liver tissue and it is a prognostic marker of human visceral
      leishmaniasis.

PMID- 18722019
TI  - The association of social support at work and in private life with mental health
      and antidepressant use: the Health 2000 Study.
AB  - BACKGROUND: Social support is assumed to protect mental health, but it is not
      known whether low social support at work increases the risk of common mental
      disorders or antidepressant medication. This study, carried out in Finland 2000
      2003, examined the associations of low social support at work and in private life
      with DSM-IV depressive and anxiety disorders and subsequent antidepressant
      medication. METHODS: Social support was measured with self-assessment scales in a
      cohort of 3429 employees from a population-based health survey. A 12-month
      prevalence of depressive or anxiety disorders was examined with the Composite
      International Diagnostic Interview (CIDI), which encompasses operationalized
      criteria for DSM-IV diagnoses and allows the estimation of DSM-IV diagnoses for
      major mental disorders. Purchases of antidepressants in a 3-year follow-up were
      collected from the nationwide pharmaceutical register of the Social Insurance
      Institution. RESULTS: Low social support at work and in private life was
      associated with a 12-month prevalence of depressive or anxiety disorders
      (adjusted odds ratio 2.02, 95% CI 1.48-2.82 for supervisory support, 1.65, 95% CI
      1.05-2.59 for colleague support, and 1.62, 95% CI 1.12-2.36 for private life
      support). Work-related social support was also associated with subsequent
      antidepressant use. LIMITATIONS: This study used a cross-sectional analysis of
      DSM-IV mental disorders. The use of purchases of antidepressant as an indicator
      of depressive and anxiety disorders can result in an underestimation of the
      actual mental disorders. CONCLUSIONS: Low social support, both at work and in
      private life, is associated with DSM-IV mental disorders, and low social support
      at work is also a risk factor for mental disorders treated with antidepressant
      medication.

PMID- 18722020
TI  - Psychopathological features of obsessive-compulsive disorder in an Italian family
      with Gilles de la Tourette syndrome not linked to the SLITRK1 gene.
AB  - We report the psychopathological features in a large Italian family with Gilles
      de la Tourette syndrome not linked to the SLITRK1 gene. Of the 23 living family
      members, 14 were evaluated using the Structured Clinical Interview for DSM-IV,
      the Yale-Brown Obsessive-Compulsive Scale, the Clinical Global Impression and the
      Global Assessment of Functioning scale. Ten patients were found to have obsessive
      compulsive disorder in which tic-like compulsions predominated. The distinctive
      feature of this family is the high frequency of obsessive-compulsive disorder
      with various clinical phenotypes.

PMID- 18722021
TI  - A new rating scale for negative symptoms: the Motor-Affective-Social Scale.
AB  - The commonly used rating scales for negative symptoms in schizophrenia have shown
      good reliability, but disagreement persists regarding both the content definition
      and the validity of several items. Instead, authors have recommended rating the
      specific behaviors that are defined as negative symptoms. To surmount these
      shortcomings, we developed a new rating scale for negative symptoms: the Motor
      Affective-Social Scale (MASS). During a 5-minute structured interview, hand
      coverbal gestures, spontaneous smiles, voluntary smiling, and questions asked by
      the interviewer were counted and rated on 101 inpatients with a diagnosis of
      schizophrenia or schizoaffective disorder. Information on social behavior was
      obtained from nursing staff. The scale consisted of a total of eight items. The
      MASS showed high internal consistency (Cronbach alpha coefficient=0.81), inter
      rater reliability, and test-retest reliability (intra-class correlation
      coefficient=0.81). Convergent validity analyses showed high correlations between
      MASS scores and scores on the Scale for the Assessment of Negative Symptom
      (SANS), and the negative symptoms subscale of the Positive and Negative Syndrome
      Scale (PANSS). The MASS showed excellent psychometric properties, practicality,
      and subject tolerability. Future research that includes the use of the MASS with
      other patient populations and that investigates the scale's sensitivity during
      clinical trials should be performed.

PMID- 18722022
TI  - Bone marrow lacking integrin expression facilitates an enhanced susceptibility to
      EAE in the xenogeneic bone marrow chimeras.
AB  - Xenotransplantation of rat bone marrow cells (BMC) into immunodeficient (SCID)
      mice generates chimeric mice susceptible to paralytic autoimmune CNS
      inflammation. Herein, we identified a disease relevant subset of transplantable
      BMC lacking expression of CD11b/c and CD49d. Moreover, disease susceptibility was
      enhanced in the presence of non-myelin specific T-cells. Only the CD11b/c
      negative population of BM retained the capability to populate the blood, spleen
      and spinal cord of recipients and matured after transplant to express CD11b/c.
      These results indicate non-myelin T cells in combination with integrin negative
      BM represent pre-pathogenic determinants of an enhanced disease susceptibility to
      myelin reactive T cells.

PMID- 18722023
TI  - Autoimmune channelopathies: John Newsom-Davis's work and legacy. A summary of the
      Newsom-Davis Memorial Lecture 2008.
AB  - John Newsom-Davis was a key figure in the field of neuroimmunology and combined
      many outstanding personal qualities with considerable clinical and scientific
      expertise. His first report of plasma exchange in myasthenia in the late 1970s
      demonstrated its use both as a treatment and as an experimental tool to establish
      the pathogenic role of antibodies in neurological disorders. Subsequent
      investigations into the Lambert Eaton myasthenic syndrome and acquired
      neuromyotonia showed that these were caused by antibodies to specific ion
      channels. The field of autoimmune channelopathies is continuing to expand with
      identification of new antibody-mediated diseases including those affecting the
      central nervous system. This review will highlight some of his most seminal
      findings and those that are following on from his work.

PMID- 18722024
TI  - Myocardial bridging in a young patient with left ventricular hypertrophy: a
      combined approach with CT scan and color Doppler echocardiography.
AB  - In this report the authors deal with the combined approach of last generation
      computed tomography and color Doppler echocardiography to make a diagnosis of
      myocardial coronary bridging in a young patient with left ventricular
      hypertrophy. Double-source tomographic scan precisely identified the tunnelled
      segment of the left descending coronary artery (the first diagonal branch),
      whereas echocardiography allowed recognising diastolic and systolic velocity just
      in this vessel. Coronary velocity throughout the bridged artery was not
      particularly increased at rest and late after exercise, even if the patient had
      ST-T changes during cycling test. These findings likely support a benign
      pathophysiological significance of isolated bridging of secondary coronary
      branches.

PMID- 18722025
TI  - Pulmonary regurgitation: the effects of varying pulmonary artery compliance, and
      of increased resistance proximal or distal to the compliance.
AB  - BACKGROUND: Pulmonary regurgitation is common after repair of tetralogy of
      Fallot, predisposing to right ventricular dilatation and potentially fatal
      arrhythmias. Magnetic resonance studies of such patients led us to hypothesize
      that the amount of regurgitation, in the absence of an effective valve, depends
      on pulmonary arterial compliance and on the location of resistance relative to
      the compliance. METHODS AND RESULTS: Using a pre-existing mathematical model
      representing the cardiovascular system, removal of the virtual pulmonary valve
      gave a triphasic pulmonary artery flow curve similar in shape to those recorded
      in patients with free regurgitation, with a regurgitant fraction of 30%. There
      was no reversal of flow at pulmonary capillary level, the regurgitant volume
      originating entirely from the compliance of the virtual pulmonary arteries and
      arterioles. Doubling their compliance increased regurgitation to 35%, whereas
      halving it decreased regurgitation to 23%. Doubling the total pulmonary vascular
      resistance by increasing arteriolar resistance increased regurgitation to 46%,
      whereas doubling it by simulating pulmonary annular stenosis proximal to the
      compliance limited regurgitation to 10%, but at the cost of a 32 mmHg peak
      systolic pressure drop. CONCLUSIONS: The model supported our hypotheses,
      indicating the relevance to pulmonary regurgitation of previously overlooked
      variables. The virtual pulmonary regurgitation was exacerbated by pulmonary
      artery compliance and by elevated resistance distal to it, but was limited by
      more proximal resistance. These relationships merit careful clinical
      investigation as they would have implications for the initial management,
      subsequent investigation and decisions on re-intervention in patients with
      pulmonary regurgitation.

PMID- 18722026
TI  - Inverted Takotsubo contractile pattern caused by pheochromocytoma with tall
      upright T-waves, but not typical deep T-wave inversion.
AB  - We describe a 36-year-old woman with inverted Takotsubo cardiomyopathy caused by
      pheochromocytoma crisis. In the acute phase, her electrocardiogram showed ST
      segment depression in lead II, III, aVF and V2 through V5. On day 14, tall
      upright T-waves were observed in leads V2 through V5 despite heart failure and
      basal to midventricular ballooning improved on day 4, and all
      electrocardiographic abnormalities finally normalized after surgical removal of
      the pheochromocytomas. This is the first report of electrocardiographic course of
      inverted Takotsubo cardiomyopathy, and these findings seem as if the inverted
      electrocardiographic findings are contrary to those of apical ballooning.

PMID- 18722027
TI  - Paroxysmal ventricular tachycardia and paroxysmal atrial fibrillation associated
      with subclinical hyperthyroidism, chronic renal failure and elevation of prostate
      specific antigen during acute myocardial infarction.
AB  - Subclinical hyperthyroidism is an increasingly recognized entity that is defined
      as a normal serum free thyroxine and free triiodothyronine levels with a thyroid
      stimulating hormone level suppressed below the normal range and usually
      undetectable. Paroxysmal atrial fibrillation is a frequent complication of acute
      myocardial infarction. It has been reported that subclinical hyperthyroidism is
      not associated with coronary heart disease or mortality from cardiovascular
      causes but it is sufficient to induce arrhythmias including an increase in atrial
      fibrillation rate. It has also been reported that increased factor X activity in
      patients with subclinical hyperthyroidism represents a potential hypercoagulable
      state. Moreover chronic renal failure presents an increased arrhythmic risk.
      Apparently spurious result has been reported in a work about mean serum prostate
      specific antigen (PSA) concentration during acute myocardial infarction with mean
      serum PSA concentration significantly lower on day 2 than either day 1 or day 3
      and it has been reported that these preliminary results could reflect several
      factors, such as antiinfarctual treatment, reduced physical activity or an acute
      phase response. We present a case of paroxysmal ventricular tachycardia and
      paroxysmal atrial fibrillation associated with subclinical hyperthyroidism,
      chronic renal failure and elevation of serum PSA concentration in a 90-year-old
      Italian man during acute myocardial infarction. Also this case focuses attention
      on the importance of a correct evaluation of subclinical hyperthyroidism and of
      chronic renal failure. Moreover, our report also confirms previous findings and
      extends the evaluation of PSA during acute myocardial infarction.

PMID- 18722028
TI  - Results of fiberoptic endoscopic evaluation of swallowing vs. radiation dose in
      the swallowing muscles after radiotherapy of cancer in the oropharynx.
AB  - BACKGROUND AND PURPOSE: Dysphagia is a serious complaint but frequently
      underreported. This paper assesses for oropharyngeal cancer (OPC) the
      relationship between the dose received by the swallowing structures, and the
      findings of a fiberoptic endoscopic evaluation of the swallowing process (FEES).
      MATERIALS AND METHODS: Between 2000 and 2005, 60 of 67 OPC patients local
      regionally NED for at least one year following treatment responded to three types
      of QoL questionnaires; i.e. Performance Status Scales, EORTC H&N35, and M.D.
      Anderson Dysphagia Inventory. Twenty-four patients agreed to the FEES procedure.
      The main swallowing muscles were delineated, with the mean dose per muscle
      calculated using the original 3D CT-based treatment plans. Regression analysis
      was performed between FEES variables and the doses in the different swallowing
      muscles and the dysphagia related questionnaires. RESULTS: A significant
      relationship was found between the results of FEES and the mean dose in the
      superior constrictor muscle (SCM). Some of the subjective dysphagia complaints
      were significantly correlated with the FEES variables in this retrospectively
      study. CONCLUSION: A higher dose in the SCM generally results in worsening of the
      findings obtained by the FEES examination.

PMID- 18722029
TI  - Effects of reduced coronary flow reserve on left ventricular function in type 2
      diabetes.
AB  - AIMS: Diabetic patients without clinical evidence of cardiovascular disease may
      develop left ventricular (LV) dysfunction. The present study was designed to test
      the hypothesis that coronary microvascular dysfunction affects LV function in
      type 2 diabetic patients. METHODS: The study subjects were 20 type 2 diabetic
      patients and 15 controls, who had been angiographically determined to have normal
      coronary arteries. LV ejection fraction (LVEF) and the percentage change in LVEF
      during dobutamine infusion (DeltaLVEF) were measured as an index of LV function.
      In order to evaluate coronary flow reserve, coronary flow velocity was recorded
      using a Doppler guide wire. RESULTS: There were no significant differences in
      LVEF. DeltaLVEF was significantly lower in the diabetic patients than in the
      control subjects (p<0.01). Although there was no significant difference in the
      baseline coronary volumetric flow between the two groups, values during maximal
      hyperemia were significantly less in the diabetic patients than in the controls
      (p<0.05). Consequently, coronary flow reserve was significantly lower (p=0.0001).
      A significant positive correlation between coronary flow reserve and DeltaLVEF
      was exhibited (r=0.68, p=0.0009). CONCLUSIONS: Coronary flow reserve, an
      indicator of coronary microvascular function, is significantly reduced in type 2
      diabetes, and this is reflected in impairment of myocardial contractile reserve.

PMID- 18722030
TI  - Serum osteoprotegerin is associated with carotid intima media thickness in women
      with previous gestational diabetes.
AB  - Circulating levels of osteoprotegerin (OPG) have been shown to be increased in
      patients with cardiovascular disorders and diabetes. The aim of this study was to
      determine serum OPG levels in women with previous gestational diabetes (GDM), and
      to investigate the relationship between OPG and carotid intima media thickness
      (IMT) and circulating cardiovascular risk factors. Serum OPG was measured in 46
      women with previous GDM and 30 age-matched healthy controls. Carotid IMT was
      evaluated. Serum lipid, insulin and hsCRP levels, plasma fibrinogen, vWF and PAI
      1 levels were measured. Serum OPG levels tended to be increased in women with
      previous GDM (p=0.058). Carotid IMT was increased in the study group. Women with
      previous GDM had elevated levels of hsCRP and PAI-1. OPG levels were positively
      correlated with age, fasting and post-load glucose levels, hsCRP, and carotid
      IMT. Multiple regression analysis showed that serum OPG was a statistically
      significant predictor for elevated carotid IMT. Our results revealed that OPG
      levels tended to be elevated in women with previous GDM. Significant association
      of OPG with carotid IMT suggested that OPG might play a role in the pathogenesis
      of endothelial dysfunction in women with previous GDM.

PMID- 18722031
TI  - Medicine access and utilization in a population covered by primary health care in
      Brazil.
AB  - OBJECTIVES: To describe medicine utilization and access in a population covered
      by the Family Health Program (PSF) in Brazil. METHODS: Cross-sectional study with
      a random sample of 2988 individuals living in areas covered by 45 PSF clinics.
      Medicine utilization in the 15 days prior to the interview was assessed, as well
      as lack of access to medicines (proportion of people with medicines needed but
      not used), and lack of free access through the PSF (proportion of medicines used
      which had to be purchased). RESULTS: Overall, 54.5% (95% CI 50.6; 58.4) of
      individuals used at least one medicine in the 15-day period and 3.6% reported
      failing to use a needed medicine. Of all medicines used, 41.5% were paid for out
      of-pocket (25.5% among the poorest families), and 51.0% were obtained for free
      from the PSF. Almost 90% of the medicines prescribed by PSF physicians were
      provided for free by the PSF. CONCLUSION: Although medicine access was high,
      individuals paid out-of-pocket for a substantial proportion of the medicines
      used. Lack of availability in PSF facilities and prescribing by non-PSF providers
      seem to contribute to the need for out-of-pocket purchases, and thus can be
      targeted for improvement through PSF policies.

PMID- 18722032
TI  - Reggies/flotillins regulate cytoskeletal remodeling during neuronal
      differentiation via CAP/ponsin and Rho GTPases.
AB  - The reggies/flotillins were discovered as proteins upregulated during axon
      regeneration. Here, we show that expression of a trans-negative reggie
      1/flotillin-2 deletion mutant, R1EA, which interferes with oligomerization of the
      reggies/flotillins, inhibited insulin-like growth factor (IGF)-induced neurite
      outgrowth in N2a neuroblastoma cells and impaired in vitro differentiation of
      primary rat hippocampal neurons. Cells expressing R1EA formed only short and
      broad membrane protrusions often with abnormally large growth cones. R1EA
      expression strongly perturbed the balanced activation of the Rho-family GTPases
      Rac1 and cdc42. Furthermore, focal adhesion kinase (FAK) activity was also
      enhanced by R1EA expression, while other signaling pathways like ERK1/2, PKC or
      PKB signaling were unaffected. These severe signaling defects were caused by an
      impaired recruitment of the reggie/flotillin-associated adaptor molecule
      CAP/ponsin to focal contacts at the plasma membrane. Thus, the reggies/flotillins
      are crucial for coordinated assembly of signaling complexes regulating
      cytoskeletal remodeling.

PMID- 18722033
TI  - Docking, 3D-QSAR studies and in silico ADME prediction on c-Src tyrosine kinase
      inhibitors.
AB  - Docking simulations and three-dimensional quantitative structure-activity
      relationship (3D-QSAR) analysis were performed on a wide set of c-Src inhibitors.
      The study was conducted using a structure-based alignment and by applying the
      GRID/GOLPE approach. The present 3D-QSAR investigation proved to be of good
      statistical value, displaying r(2), q(2) and cross-validation SDEP values of
      0.94, 0.84 and 0.42, respectively. Moreover, such a model also proved to be
      capable of predicting the activities of an external test set of compounds. The
      availability of the 3D structure of the target made possible the interpretation
      of steric and electrostatic maps within the binding site environment and provided
      useful insight into the structural requirements for inhibitory activity against c
      Src. Two regions whose occupation by hydrophobic portions of ligands would
      favourably affect the activity were clearly identified. Moreover, hydrogen bond
      interactions involving residues Met343, Asp406 and Ser347 emerged as playing a
      key role in determining the affinity of the active inhibitors toward c-Src.
      Furthermore, the inhibitors bearing a basic nitrogen provided enhanced potency
      through protonation and salt bridge formation with Asp350. A preliminary
      pharmacokinetic profile of the molecules under analysis was also drawn on the
      basis of Volsurf predictions.

PMID- 18722034
TI  - Synthesis and investigation of anti-inflammatory activity and gastric
      ulcerogenicity of novel nitric oxide-donating pyrazoline derivatives.
AB  - A group of 3,5-diaryl-2-pyrazoline derivatives were prepared via the reaction of
      various chalcones with hydrazine hydrate in ethanol. A group of NO-donating-2
      pyrazoline derivatives were synthesized by carrying a nitrate ester group or an
      oxime group onto the prepared pyrazoline derivatives through different spacers.
      The prepared compounds were evaluated for their anti-inflammatory activity using
      carrageenan-induced rat paw edema and compared to a well-known NSAID,
      indomethacin as a reference drug. The ability of the prepared compounds to induce
      gastric toxicity was also evaluated. Most of the prepared compounds showed
      significant anti-inflammatory activity at the injected dose (100mg/kg) but they
      were safer than indomethacin in regard to gastric toxicity. The incorporation of
      the NO-donating group into the parent pyrazoline derivatives caused a non
      significant reduction in the anti-inflammatory activity while a marked decrease
      in gastric ulcerations induced by their parent pyrazolines was observed.

PMID- 18722035
TI  - Synthesis of novel benzo[h]quinolines: wound healing, antibacterial, DNA binding
      and in vitro antioxidant activity.
AB  - We have characterized a new class of 2-mercapto/2-selenobenzo[h]quinoline-3
      carbaldehyde (3/4). Antibacterial potential of these compounds against a wide
      range of gram-positive and gram-negative bacteria was studied. The selenium
      containing compound 4 showed significant inhibition zone on Staphylococcus aureus
      (22.76+/-0.14), Bacillus subtilis (20.63+/-0.24), and Streptococcus pyogenes
      (19.54+/-0.20) over sulfur containing compound 3. To validate the
      ethnotherapeutic claims of the synthetic compounds in skin diseases, wound
      healing activity was studied, besides antioxidant activity to understand the
      mechanism of wound healing. The interaction behavior of these compounds with DNA
      was investigated by absorption spectra (obtained K(b) constant for 3 is 2.7x10(5)
      and for 4 is 3.8x10(6)), viscosity, and thermal denaturation studies. Finally,
      the results show that the DNA intercalated 3/4 compounds are strong antioxidants;
      they show significant wound healing activity and protect oxidative DNA damage
      from harmful free radical reactions.

PMID- 18722036
TI  - Regioselective synthesis and antimicrobial screening of novel
      ketocarbazolodispiropyrrolidine derivatives.
AB  - A series of novel dispiropyrrolidine derivatives have been synthesized through
      1,3-dipolar cycloaddition reaction of azomethine ylide generated from sarcosin
      and di/tri ketone with the dipolarophile (E)-2-arylidine-1-keto-carbazoles. The
      cycloadducts ketocarbazalo spiro N-methyl pyrrolidines showed the most
      interesting antimicrobial activity at lower concentration.

PMID- 18722037
TI  - [Malignant degeneration of benign cystic teratoma of the ovary with synchronous
      mediastinal teratoma. A case report].
AB  - Squamous cell carcinoma arising in mature cystic teratoma of the ovary is an
      uncommon complication occurring usually in elderly woman. We present an unusual
      case of a post-menopausal woman with a synchronous mediastinum teratoma. While
      ovary tumor was symptomatic, mediastinal teratoma was an incidental finding. To
      the best of our knowledge, this association is the first to be reported in
      literature.

PMID- 18722038
TI  - Seeing the forest and the trees: using network analysis to develop an
      organizational blueprint of state tobacco control systems.
AB  - In the United States, tobacco control activities are organized primarily in state
      tobacco control programs. These programs are comprised of public and private
      agencies working together to reduce tobacco use. The human, financial, and
      informational resources that go into state tobacco control programs are
      documented, and the outcomes of these programs have been studied in terms of
      health and health behavior. However, little is known about the organizational
      infrastructure that transforms the human, financial, and informational resources
      into positive health outcomes. This study examined the inter-organizational
      relationships among key partner agencies in eight state tobacco control programs.
      The state programs varied in terms of funding level, funding stability, and
      region of the country. Using a network analytic approach we asked an average of
      14 agencies in each state program about their contacts and partnerships with the
      other key tobacco control agencies in their state program. Using network
      visualization and statistics we determined that the state networks shared some
      common features such as a highly central lead agency, but also had differences in
      network structure in terms of density and centralization. Using blockmodeling we
      found that, despite differences in state and program characteristics, there was a
      common organizational structure among the eight state programs. Understanding the
      inter-organizational relationships and the common organizational structures of
      state programs can aid researchers and practitioners in enhancing program
      capacity and in developing strategies for organizing effective public health
      systems.

PMID- 18722039
TI  - A double blind randomized clinical trial of at-home tooth bleaching using two
      carbamide peroxide concentrations: 6-month follow-up.
AB  - OBJECTIVES: This double blind randomized clinical trial evaluated the longevity
      of the whitening effect (6-month follow-up) of two carbamide peroxide
      concentrations used in at-home vital bleaching. METHODS: Ninety-two volunteers
      with shade mean C1 or darker for the six maxillary anterior teeth were randomized
      into two balanced groups (n=46) according to bleaching agent concentration: 10%
      (CP10) or 16% (CP16) carbamide peroxide. Patients were instructed to use the
      whitening agent in a tray for 2h/day during 3 weeks. Shade evaluations were done
      with a value-oriented shade guide, and a spectrophotometer at baseline, and at 1
      week and 6-month post-bleaching. Volunteers for both treatment groups had to
      answer questions related to dietary and oral hygiene behavior. RESULTS: At 6
      month recall, tooth shade remained significantly lighter than at baseline, in
      both treatment groups, considering the color parameters: DeltaL, Deltaa, Deltab,
      DeltaE (p<0.0001) or the tooth shade median values (p<0.001). Additionally, shade
      median relapse at 6-month follow-up was not statistically different between CP10
      and CP16 groups using the spectrophotometer (p=0.1) or the visual matching
      (p=0.7) analyses. Overall, subjects from CP10 and CP16 reported high consumption
      of beverage and food stains, which was not different between groups (p=0.5).
      CONCLUSIONS: The whitening effect remained similar 6-month after the bleaching
      treatment for both carbamide peroxide concentrations tested. Additionally, the
      high consumption of staining beverages and foods reported by patients had no
      influence in the whitening effect longevity at 6-month.

PMID- 18722040
TI  - Assessment of the role of timing of second transplantation in multiple myeloma by
      multistate modeling.
AB  - OBJECTIVE: Stem cell transplantation has a place in the management of many
      patients with hematological disorders, but is no longer the final and definitive
      treatment for most of these individuals. The relapsing patient may be offered
      further therapy, and evaluating the contribution of the treatments available has
      become statistically challenging. This study was designed to evaluate further the
      benefit and timing of double autologous transplantation in the management of
      patients with myeloma. MATERIALS AND METHODS: We investigated the potential
      benefit of a second autologous transplantation for myeloma before relapse or
      progression ("elective" transplantation) and the importance of the timing of the
      procedure using a multistate approach. We used data from 7452 patients with
      myeloma who received autologous transplantation and who were reported to the
      registry of the European Group for Blood and Marrow Transplantation. RESULTS:
      With use of statistical and visual models, the multistate approach shows the
      benefit of being able to undergo a second transplantation within 12 months of the
      first transplantation. CONCLUSION: Our study focuses on the importance of
      appropriate statistical analysis and illustrates how use of the Cox model within
      a multistate framework may be applied to the assessment of the role of an
      intermediate event in the disease process. The study illustrates both
      mathematically and visually the improved survival resulting from undertaking an
      elective second transplantation in patients with myeloma as soon as medically
      prudent-usually within 3 to 6 months of the first transplantation.

PMID- 18722041
TI  - Use of Nramp2-transfected Chinese hamster ovary cells and reticulocytes from
      mk/mk mice to study iron transport mechanisms.
AB  - OBJECTIVE: We investigated mechanisms involved in iron (Fe) transport by DMT1
      (endosomal Fe(II) exporter, encoded by the Nramp2 gene) using wild-type Chinese
      hamster ovary (CHO) cells and Nramp2-transfected CHO cells, as well as
      reticulocytes from normal and mk/mk mice that have a defect in DMT1. MATERIALS
      AND METHODS: CHO cells and reticulocytes were incubated with 59Fe bound to
      various ligands. The radioiron was present in its Fe(II) or Fe(III) forms or
      bound to transferrin (Tf), and the internalized 59Fe measured under varying
      experimental conditions. Additionally, 125I-Tf interaction with reticulocytes was
      investigated and 59Fe incorporation into their heme was determined. RESULTS:
      Hyperexpression of DMT1 in CHO cells greatly increases their capacity to acquire
      ferrous iron. Although CHO-Nramp2 cells showed an increase in Fe(III) uptake as
      compared to CHO cells, they transported Fe(III) with much lower efficacy than
      Fe(II). In addition to their defect in Fe uptake, mk/mk reticulocytes also showed
      a decrease in Tf receptor levels. CONCLUSIONS: Given that CHO cells acquire iron
      from Fe(II)-ascorbate with much higher rates than from Fe(III)-Tf, Tf-receptor
      levels represent the rate-limiting step in their iron uptake. As Fe(III)
      transport by CHO-Nramp2 cells can be inhibited by the impermeable oxidant
      K3Fe(CN)6, a membrane ferric reductase is probably needed for reduction of
      Fe(III) to Fe(II), which is then transported by DMT1. DMT1 is not a limiting
      factor in Fe acquisition by normal reticulocytes and their heme synthesis.

PMID- 18722042
TI  - Nonhuman primate allogeneic hematopoietic stem cell transplantation by
      intraosseus vs intravenous injection: Engraftment, donor cell distribution, and
      mechanistic basis.
AB  - OBJECTIVE: The traditional intravenous (IV) route of administration for
      hematopoietic stem cell transplantation (HSCT) may result in inefficient
      placement of donor cells, possibly contributing to suboptimal engraftment and
      higher risk of graft-vs-host reactions. In order to perform detailed studies of
      engraftment and donor cell distribution in an animal model with anatomical
      similarity to man, we performed the first direct homing/engraftment efficiency
      comparison between intraosseus (IO) and IV HSCT in allogeneic nonhuman primate
      animal model to assess the utility and mechanism of donor cell homing after IO
      delivery. MATERIALS AND METHODS: Donor bone marrow (BM) cells labeled with PKH26
      membrane dye were transplanted to nonmyeloablative-conditioned nonhuman primate
      animals. Chimerism was confirmed by polymerase chain reaction amplification of
      donor-specific short tandem repeat locus. RESULTS: Compared to the IO route, IV
      infusion trapped 2.4- to 4.8-fold more donor cells in peripheral organs,
      including the lung, heart, spleen, kidney, and liver. IO injection resulting in a
      6.2-fold increase in donor cells retained in the BM at the site of injection and
      a 2.7-fold increase in donor cells retained in distant BM sites. A profile of
      selected cell adhesion molecules (CAMs) demonstrated that after IO HSCT, more
      donor cells express CAMs that could facilitate BM homing and redistribution to
      non-injection-side BM cavities. This change in homing efficiency may be
      clinically significant because IO transplantation in haploidentical recipients
      enhanced donor cell engraftment when compared to IV delivery. CONCLUSION: Our
      results suggest that IO injection enhances both homing and engraftment in
      nonhuman primate HSCT.

PMID- 18722043
TI  - Editorial comment on: Bladder preservation in selected patients with muscle
      invasive bladder cancer by complete transurethral resection of the bladder plus
      systemic chemotherapy: long-term follow-up of a phase 2 nonrandomized comparative
      trial with radical cystectomy.

PMID- 18722044
TI  - Editorial comment on: Bladder preservation in selected patients with muscle
      invasive bladder cancer by complete transurethral resection of the bladder plus
      systemic chemotherapy: long-term follow-up of a phase 2 nonrandomized comparative
      trial with radical cystectomy.

PMID- 18722045
TI  - Editorial comment on: External beam radiation therapy followed by interstitial
      radiotherapy with iridium-192 for solitary bladder tumours: results of 111
      treated patients.

PMID- 18722046
TI  - Bladder preservation in selected patients with muscle-invasive bladder cancer by
      complete transurethral resection of the bladder plus systemic chemotherapy: long
      term follow-up of a phase 2 nonrandomized comparative trial with radical
      cystectomy.
AB  - BACKGROUND: Many phase 2 bladder-sparing programmes using transurethral resection
      of the bladder (TURB) plus chemotherapy or radio-chemotherapy have been
      undertaken, but some controversies remain. OBJECTIVE: To determine the efficacy
      of complete TURB plus three cycles of cisplatin-based chemotherapy in selected
      patients with muscle-invasive bladder cancer (MIBC). DESIGN, SETTING, AND
      PARTICIPANTS: A phase 2 nonrandomized trial was designed that included patients
      with MIBC who underwent complete TURB with positive biopsies of the tumour bed.
      Patients with negative biopsies of the tumour bed, with macroscopically residual
      tumour, with hydronephrosis, or with distant metastasis were excluded from this
      trial. Patients included in this trial were offered three cycles of systemic
      chemotherapy or radical cystectomy (RC). Clinical response (cR) was denoted by
      either no tumour or the presence of Ta1-Tis bladder tumour at 3-mo evaluation;
      clinical non-response (cNR) was denoted by cases of muscle-invasive tumour or
      distant metastasis. Of 146 patients who entered this trial, 75 choose the bladder
      sparing programme and 71 chose RC. MEASUREMENTS: At 5 yr and 10 yr, the cancer
      specific survival (CSS) rate was 64.5% and 59.8%, respectively, with no
      significant difference compared to the RC arm (p=0.544). The progression-free
      survival with bladder preserved was 52.6% and 34.5%, respectively. In
      multivariate analysis, cR was the only predictive factor for survival (p=0.001)
      and bladder preservation (p=0.000). RESULTS AND LIMITATIONS: This was not a
      randomized trial, and patients were included over 16 yr. However, no
      modifications were made to the therapy schedule except from chemotherapy schemes
      considered standard at the time. CONCLUSIONS: Patients with microscopic residual
      cancer after complete TURB seem to be good candidates for the bladder-sparing
      programme using three cycles of systemic chemotherapy, with CSS comparable to RC.

PMID- 18722047
TI  - Editorial comment on: External beam radiation therapy followed by interstitial
      radiotherapy with iridium-192 for solitary bladder tumours: results of 111
      treated patients.

PMID- 18722050
TI  - Thymidylate synthase genotypes and tumour regression in stage II/III rectal
      cancer patients after neoadjuvant fluorouracil-based chemoradiation.
AB  - PURPOSE: According to the CAO-/ARO-/AIO-94 trial of the German Rectal Cancer
      Study Group, pre-operative 5-fluorouracil (5-FU)-based long-term
      chemoradiotherapy (CT/RT) is recommended for patients with rectal cancer UICC
      stage II/III. However, despite the local benefit of neoadjuvant treatment, the
      overall prognostic value remains uncertain in comparison to adjuvant CT/RT. We
      assessed the impact of standardized pre-operative CT/RT and intratumoural mRNA
      levels and polymorphisms of the TS gene on histopathological tumour regression.
      PATIENTS AND METHODS: 40 patients with rectal cancer UICC stage II/III, receiving
      pre-operative 5-FU-based CT/RT followed by standardized surgery, including total
      mesorectal excision, were investigated. TS gene expression and TS polymorphisms
      of surgical specimens were correlated with the grade of histopathological tumour
      regression (0-4). Patients achieved regression grades 2-4 were determined as
      responders. RESULTS: TS polymorphisms (5'-28bp repeat+G/C SNP and TS1494del6)
      could be determined in 39/40 (97.5%) and in 38/40 (95%) patients, respectively.
      Quantification of TS mRNA expression was successful in 36/40 (90%) patients.
      There was a highly significant linkage disequilibrium between 5'- and 3'-TS
      polymorphisms (p=0.0013). Interestingly, the majority of patients (82.1%) with 5'
      TS genotypes known to be associated with low mRNA expression (2R/2R, 2R/3RC,
      3RC/3RC) also possessed the TS1494del6 +6bp/+6bp genotype correlating with high
      TS mRNA expression. TS1494del6 polymorphism was significantly associated with TS
      mRNA expression. Patients with TS1494del6 -6bp/-6bp or -6bp/+6bp genotypes showed
      significantly lower mean TS mRNA expression with 0.55 (range:0.33;0.84) as
      compared to +6bp homozygotes with a mean expression of 0.90 (range:0.20;1.91)
      (p=0.025). Furthermore, all patients with TS 3'-UTR -6bp/-6bp or -6bp/+6bp
      genotype (11/11) were responders as compared to only 20/26 (77%) of patients with
      TS 3'-UTR +6bp/+6bp genotype (p=0.082). TS 5'-polymorphisms were not associated
      with neither tumour regression nor gene expression. CONCLUSION: Our data suggest
      that the TS1494del6 polymorphism may be an important predictor for
      histopathological tumour regression in UICC II/III rectal cancer patients
      receiving neoadjuvant 5-FU-based CT/RT.

PMID- 18722048
TI  - External beam radiation therapy followed by interstitial radiotherapy with
      iridium-192 for solitary bladder tumours: results of 111 treated patients.
AB  - BACKGROUND: Evaluation of bladder-preserving treatment protocol. OBJECTIVE: To
      evaluate the long-term results of iridium-192 brachytherapy-based bladder-sparing
      treatment strategy in patients with solitary invasive bladder tumours. DESIGN,
      SETTING, AND PARTICIPANTS: We performed a retrospective analysis of 111 patients
      with solitary T1G3-T2Gall bladder tumours (< or = 5 cm), who were treated with
      iridium-afterloading brachytherapy between February 1988 and May 2007.
      INTERVENTION: After transurethral tumour resection, external beam radiotherapy
      (28 Gy; 12 fractions) was given, followed by brachytherapy (Iridium-192; 40 Gy).
      Partial cystectomy was part of the treatment strategy in nine patients. In five
      of those patients a T3 tumour was found, and they were included in the analysis.
      MEASUREMENTS: The 5-, 10- and 15-yr overall survival rate (OS); disease-specific
      survival rate (DSS); and disease-free survival rate (DFS) estimates were
      determined using the Kaplan-Meier method. RESULTS AND LIMITATIONS: Mean follow-up
      period was 6.2 yr (range: 0.2-16.3 yr). At the last follow-up 75 patients were
      alive without evidence of disease, whereas 17 patients had died without evidence
      of disease. Nineteen patients died of bladder cancer after a mean follow-up
      period of 2.9 yr (range: 0.5-9.0). OS rates at 5 yr, 10 yr, and 15 yr were 70%,
      55%, and 51%, respectively. DSS rates at 5 yr, 10 yr, and 15 yr were 82%, 73% and
      73%, respectively. DFS rates at 5 yr, 10 yr, and 15 yr were 60%, 47%, and 23%,
      respectively. Higher tumour stage (T3 vs T1) was negatively associated with DSS
      (hazard ratio [HR]:19.8; p=0.01) and DFS (HR: 4.67; p=0.02). No prognostic factor
      was found for OS. Local recurrence occurred in 27% of patients and salvage
      cystectomy was performed in 9% of patients. Bladder function was able to be
      preserved in 99 of 111 patients (89%). CONCLUSIONS: In patients with solitary
      stage T1-T2 bladder cancer (< or = 5 cm) who refuse radical cystectomy or who are
      poor candidates for major surgical procedures, this modality is a valuable
      treatment alternative.

PMID- 18722051
TI  - A novel and effective hepatocyte growth factor kringle 1 domain and p53 cocktail
      viral gene therapy for the treatment of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, yet
      effective therapeutic options for advanced HCC are limited. Kringle 1 domain of
      HGF (HGFK1) has been demonstrated as a potent anti-tumor molecule and p53 is a
      well established tumor suppressor. Recently we developed AAV transducing HGFK1
      (AAV-HGFK1) as a gene therapy for HCC. Here we investigated the possibility of
      enhancing the effect of AAV-HGFK1 by combining it with Adv transducing p53 (Adv
      p53). In vitro expression experiments suggested a small amount of Adv-p53 could
      increase the expression of AAV transgenes. AAV-HGFK1+Adv-p53 cocktail strongly
      inhibited the proliferation of microvascular endothelial cell (MEC) and two HCC
      cell lines, Hepa1-6 and McA-RH7777. In two orthotopic mice and rat HCC models the
      cocktail gene therapy also significantly reduced the tumor burdens and prolonged
      the survival time by inhibiting tumor angiogenesis and inducing tumor cell death.
      Significantly, tumor metastasis was completely prevented. AAV-HGFK1+Adv-p53 viral
      cocktail may be a promising cancer therapy for the treatment of HCC.

PMID- 18722052
TI  - Supported Cu(II) polymer catalysts for aqueous phenol oxidation.
AB  - Supported Cu(II) polymer catalysts were used for the catalytic oxidation of
      phenol at 30 degrees C and atmospheric pressure using air and H(2)O(2) as
      oxidants. Heterogenisation of homogeneous Cu(II) catalysts was achieved by
      adsorption of Cu(II) salts onto polymeric matrices (poly(4-vinylpyridine),
      Chitosan). The catalytic active sites were represented by Cu(II) ions and showed
      to conserve their oxidative activity in heterogeneous catalysis as well as in
      homogeneous systems. The catalytic deactivation was evaluated by quantifying
      released Cu(II) ions in solution during oxidation, from where Cu-PVP(25) showed
      the best leaching levels no more than 5 mg L(-1). Results also indicated that Cu
      PVP(25) had a catalytic activity (56% of phenol conversion when initial Cu(II)
      catalytic content was 200 mg L(Reaction)(-1)) comparable to that of commercial
      catalysts (59% of phenol conversion). Finally, the balance between activity and
      copper leaching was better represented by Cu-PVP(25) due to the heterogeneous
      catalytic activity had 86% performance in the heterogeneous phase, and the rest
      on the homogeneous phase, while Cu-PVP(2) had 59% and CuO/gamma-Al(2)O(3) 68%.

PMID- 18722053
TI  - Biosorption of Cr(III) using in natura and chemically treated tropical peats.
AB  - The physicochemical characteristics of three Brazilian peats were investigated
      using elemental analysis, scanning electron microscopy (SEM), X-ray
      diffractometry (XRD) and studies of Cr(III) biosorption based on adsorption
      isotherms. Adsorption of Cr(III) by in natura peat from Santo Amaro das Brotas
      (Sergipe State) was much greater than by peats from either Ribeirao Preto (Sao
      Paulo State) or Itabaiana (Sergipe State), with adsorption capacities (q) of
      4.90+/-0.01, 1.70+/-0.01 and 1.40+/-0.01 mg g(-1), respectively. Pre-treatments
      with HCl and NaOH+HCl reduced adsorption by the Santo Amaro das Brotas peat,
      showing that adsorption efficiency was associated with the amount of organic
      matter present. Conversely, increase in the mineral content following pre
      treatment increased adsorption of Cr(III) by the Ribeirao Preto and Itabaiana
      peats. Highest adsorption (retention >95.0%) was achieved at equilibrium pH 4.0
      using the Santo Amaro das Brotas peat. Experimental data for the adsorption of
      Cr(III) from aqueous solution onto this peat were fitted to the Langmuir
      equation, from which an equilibrium adsorption capacity, q(max), of 5.60 mg g(-1)
      was obtained, which was close to the experimentally determined value.

PMID- 18722054
TI  - Isolation and characterization of a Cr(VI)-reduction Ochrobactrum sp. strain CSCr
      3 from chromium landfill.
AB  - A strain CSCr-3 with high Cr(VI)-reducing ability under alkaline conditions was
      isolated from a chromium landfill and identified as Ochrobactrum sp. on the basis
      of 16S rRNA gene sequence analysis. The cells were rod shaped, Gram-negative and
      motile. The physiological characteristics and Cr(VI)-reduction of the strain were
      also studied. The results showed that the Ochrobactrum sp. strain CSCr-3 was
      tolerant to very high concentration of Cr(VI) (800 mg/L) and capable of reducing
      different forms of Cr(VI) (chromate and dichromate), under a wide range of
      temperatures (25-40 degrees C) and pH (7-11) with optimum at 35 degrees C and
      initial pH 10. Higher rates of Cr(VI)-reduction were observed with higher initial
      cell and Cr(VI) concentrations. Strain CSCr-3 could reduce Cr(VI) very
      efficiently over a wide range of Cr(VI) concentrations (100-800 mg/L). The
      addition of glucose caused a dramatic increase in Cr(VI)-reduction by
      Ochrobactrum sp. CSCr-3, while the presence of sulfate or nitrate had no
      influence. The presence of other metals, such as Cu, Co, Mn, etc., significantly
      stimulated Cr(VI)-reduction ability by the strain CSCr-3. The results obtained in
      this study have significance for the bioremediation of chromate pollution.

PMID- 18722055
TI  - Aerobic biodegradation of 2,4-DNT and 2,6-DNT: performance characteristics and
      biofilm composition changes in continuous packed-bed bioreactors.
AB  - This manuscript deals with continuous experiments for biodegradation of
      individual dinitrotoluenes by a defined mixed culture in packed-bed reactors
      (PBRs) containing either poraver or fire-clay as packing material. Removal
      efficiencies and volumetric biodegradation rates were measured as a function of
      the loading rate of 2,4-dinitrotoluene (2,4-DNT) and 2,6-dinitrotoluene (2,6-DNT)
      under steady-state conditions. The poraver reactor showed higher removal
      efficiencies for both the DNTs. The removal efficiency for 2,4-DNT remained
      greater than 90% in the poraver reactor whereas it dropped steadily from 85 to
      65% in the fire-clay reactor as the organic loading rates were increased from 19
      to 60 mg L(-1)day(-1). Similar trends were seen for the volumetric degradation
      rate as well. In both the reactors, 2,4-DNT degraded more effectively than 2,6
      DNT. The microbial consortium was characterized both in the inoculum as well as
      in the operating PBR. Cell numbers per gram dry packing material were similar in
      the two reactors. However, there was a distinct difference in the nature of
      microorganisms that were found in the two packings. The fire-clay contained a
      larger number of cells that were not primary degraders of DNTs.

PMID- 18722056
TI  - Introduction of threat analysis into the land-use planning process.
AB  - The subject of this paper is a method for introducing risk assessment into the
      land-use planning (LUP) process. Due to adaptations of the results of risk
      assessment, which are needed to make the risk assessment usable by land-use
      planners, we term the overall process threat analysis. The key features of the
      threat analysis can be summarised as follows. (i) It consists of three main
      steps. The first is determination of the threat intensity level of an accident,
      the second is analysis of the environmental vulnerability of the surroundings of
      an accident, and the third, integrating the previous two, is determination of a
      threat index in the accident impact zone. All three are presented in GIS based
      maps, since this is a common expression in LUP. (ii) It can and should be applied
      in the early stages of the LUP process. The methodology is illustrated by an
      example in the context of renewal of a land-use plan for the Municipality of
      Koper in Slovenia. The approach of threat analysis follows directions of the
      Article 12 of the Directive 96/82/EC of the European Commission (the Seveso II
      Directive).

PMID- 18722057
TI  - Effect of amended soil and hydraulic load on enhanced biological nitrogen removal
      in lab-scale SWIS.
AB  - To characterize the effect of amended soil on nitrogen removal in subsurface
      wastewater infiltration system (SWIS), culture, grass carbon, and zeolite were
      mixed to produce microbial inoculums, and then the optimal microbial inoculums,
      nutrient substance, cinder, and original soil were mixed to produce the soils
      through bioaugmentation. Results indicate that the microbial inoculums
      (culture+50% grass carbon+50% zeolite) and the amended soil (12.5% microbial
      inoculums+25% nutrient substrate+12.5% cinder+50% original soil) have the optimal
      biogenic stimulating properties, and the adsorption capacity of the amended soil
      are 1.216 mg-Pg(-1) and 0.495 mg-Ng(-1). The laboratory soil column experiment
      indicates that the efficient mode of nitrogen removal in lab-scale SWIS is
      adsorption-nitrification-denitrification and the nitrification/denitrification
      can be enhanced by the application of the amended soil. On average, the SWIS
      filled with amended soil converts 85% of ammonia nitrogen (NH(4)(+)-N) to NO(x)(
      )-N and removes 49.8-60.6% of total nitrogen (TN), while the system filled with
      original soil removes 80% of NH(4)(+)-N and 31.3-43.2% of TN at 4-8 cm day(-1).
      Two systems are overloads at 10 cm day(-1). It is concluded that the microbial
      activities and nitrogen removal efficiencies are improved in SWIS after
      bioaugmentation.

PMID- 18722058
TI  - Calorimetric study of peroxycarboxylic ester synthesis.
AB  - Exothermic reactions involving organic peroxides carry a high potential hazard
      and must be considered with care. A safe handling requires, among others, the
      assessment of thermal process safety, for which safety characteristics like
      overall heat production and the resulting adiabatic temperature rise are
      essential. The article presents the results of the calorimetric investigation of
      the synthesis of four peroxycarboxylic esters, three tert-Butyl and one tert-Amyl
      peroxycarboxylic ester. In the two-step synthesis the second one clearly shows
      the higher exothermic potential. The overall heat production lies in the range of
      126-135 kJ/mol and is nearly independent of the carboxylic acid residual in the
      tert-Butyl peroxycarboxylic ester. The calculated adiabatic temperature rise is
      70-80K. Influence of temperature and feed rate on the heat generation is
      discussed for one species. A grading of the synthesis with respect to temperature
      levels according to the criticality classes by Stoessel leads to the most
      critical for an exothermic reaction.

PMID- 18722059
TI  - Studying effect of cell wall's carboxyl-carboxylate ratio change of Lemna minor
      to remove heavy metals from aqueous solution.
AB  - The pre-treated Lemna minor can remove Hg(II), Cr(III), Cr(VI) and Cu(II) from
      the aqueous solution. The concentration determination of carboxyl and carboxylate
      groups and its rule to change the metal ions uptake was done by the curves of the
      potentiometric titration. It was shown that the removal percent of the heavy
      metal ions (Co=1.00 mM) increased 25.1, 26.0, 17.2 and 24.1% for these ions,
      respectively, with increasing the carboxylate from 0.92 to 2.42 mmol/g L. minor
      and then activating by the activator chloride salts. The removal percent of these
      ions was decreased 33.1, 27.5, 20.7 and 15.01%, respectively, with increasing the
      carboxyl from 1.50 to 2.41 mmol/g L. minor, inspite of activating by the chloride
      salts. The enthalpy change (DeltaH) was -27.43, -25.94, -28.12 and -22.27 kJ/mol
      and the entropy change (DeltaS) was 81.3, 79.9, 86.1 and 67.7 J/mol K, by
      activated biomass, respectively. L. minor removed these heavy metals
      corresponding to pseudo-second-order kinetic model that the activation energy
      (E(a)) was obtained 18.59, 15.93, 20.36 and 21.12 kJ/mol by the activated and
      23.02, 22.27, 23.98 and 24.46 kJ/mol by the reference biomass to uptake Hg(II),
      Cr(III), Cr(VI) and Cu(II), respectively.

PMID- 18722061
TI  - Preparation of TEM samples for hard ceramic powders.
AB  - It is challenging to prepare a good sample for high-resolution electron
      microscopy of polycrystalline ceramic powders containing hard particles or
      particles with a strong preferential cleavage. Here we demonstrate that embedding
      the particles in a Cu matrix in a pressed pellet allows for straightforward
      conventional ion milling. The method is applied to powders of Mg10Ir19B16 and
      Na0.5CoO2 to show its feasibility, whereby transmission electron microscopy (TEM)
      samples with crystalline areas thinner than 10 nm can be obtained easily.

PMID- 18722062
TI  - Why is your spouse so predictable? Connecting mirror neuron system and self
      expansion model of love.
AB  - The simulation theory assumes we understand actions and intentions of others
      through a direct matching process. This matching process activates a complex
      brain network involving the mirror neuron system (MNS), which is self-related and
      active when one does something or observes someone else acting. Because social
      psychology admits that mutual intention's understanding grows in close
      relationship as love grows, we hypothesize that mirror mechanisms take place in
      love relationships. The similarities between the mirror matching process and the
      mutual intention's understanding that occurs when two persons are in love suggest
      that exposure to love might affect functional and neural mechanisms, thus
      facilitating the understanding of the beloved's intentions. Congruent with our
      hypothesis, our preliminary results from 38 subjects strongly suggest a
      significant facilitation effect of love on understanding the intentions of the
      beloved (as opposed to control stimuli). Based on these phenomenological, and
      neurofunctional findings we suggest that the mirror mechanisms are involved in
      the facilitation effects of love for understanding intentions, and might further
      be extended to any types of love (e.g., passionate love, maternal love). Love
      experiences are important not only to the beloved himself, but also to any
      societal, cultural, and institutional patterns that relate to love. Yet,
      concerning its subjective character, love experiences are difficult to access.
      The modern procedures and techniques of socio-cognitive neuroscience make it
      possible to understand love and self-related experiences not only by the analysis
      of subjective self-reported questionnaires, but also by approaching the automatic
      (non-conscious) mirror experiences of love in healthy subjects, and neurological
      patients with a brain damage within the mirror neuron system. Although the
      psychology of love is now well admitted, the systematic study of the automatic
      facilitation effect of love through mirror mechanisms might open a new avenue
      towards the social mind and also self consciousness.

PMID- 18722063
TI  - [Missed opportunities of in utero transfer of very preterm births (24-32 weeks
      gestation) in Aquitaine, 2003-2005].
AB  - OBJECTIVE: Describe and define the factors associated with missed opportunities
      of an in utero transfer (IUT), defined by by an absence of IUT where there was no
      counter-indication for a transfer. MATERIALS AND METHODS: Multicentric and
      retrospective cohort study within the Aquitaine perinatal healthcare network from
      1st January 2003 to 30th June 2005 on deliveries between 24 and 32 weeks
      gestation, depending on whether the woman initially followed care in level I or
      II facilities benefited from an IUT at a level III facility or not. associated
      with missed opportunities of IUT were analysed by a logistic regression. RESULTS:
      Five hundred and twelve deliveries, eligible to deliver in level III facilities,
      were included in the study: 273 after an IUT and 239 in a level I or II maternity
      hospitals out of which 18% are defined as a missed opportunity of an in utero
      transfer. The multivariate analysis did not show a link between missed
      opportunities of an in utero transfer and the characteristics of maternities:
      status, size, level of care and distance from a level III facility. Only the
      delivery term appears to be linked to a missed opportunity of an in utero
      transfer (p=0.01): 32 weeks gestation versus 26-29 weeks gestation (RC=6.53;
      IC(95%): 2.00-21.25). While managing the delivery after 31 weeks gestation is
      considered suitable in a level IIb facility, the delivery term is no longer
      statistically related to a missed opportunity. CONCLUSION: This study serves as a
      first analysis of the Aquitaine perinatal healthcare network. It shows that
      missed opportunities of IUT does not seem to be linked to characteristics of
      maternities but seems to be linked to deliveries after 31 weeks gestation in
      level IIb facilities.

PMID- 18722064
TI  - [Results of a prospective standardized study of 30 patients with chronic
      neurological and cognitive disorders after tick bites].
AB  - OBJECTIVE: Patients with chronic neurological disorders and cognitive impairment
      after tick bites are difficult to manage despite standard antibiotic therapy for
      Lyme disease. We wanted to correctly assess the disorders. METHODS: Thirty
      patients were hospitalized for a standardized evaluation of their disorders:
      clinical examination, biological and serological studies, cerebral MRI, CSF
      study, neurophysiological exams, and neuropsychological evaluation of cognitive
      functions. RESULTS: Clinical and biological results were non informative. We
      observed significant CSF abnormalities (64%), MRI Flair pictures (41%),
      neurophysiological exams (47%), and cognitive evaluation (100%). CONCLUSIONS: A
      large and standardized evaluation should be made for each patient to improve the
      management and probably the treatment of these complex chronic symptoms observed
      after tick bites.

PMID- 18722065
TI  - [Routine use of extended-release clarithromycin tablets for short-course
      treatment of acute exacerbations of non-severe COPD].
AB  - OBJECTIVE: This study was designed to confirm, in routine clinical practice
      conditions, the success rates and safety of extended-release clarithromycin
      tablets in patients with acute exacerbation of chronic obstructive pulmonary
      disease (COPD), according to the usual empirical criteria in routine clinical
      practice. PATIENTS AND METHODS: An open-label, pharmacoepidemiological, clinical
      study in community practice was performed with 180 practitioners. The bacterial
      origin was suspected when sputum was obviously purulent. RESULTS: Seven hundred
      and nineteen adult patients with acute exacerbation of mild or moderately severe
      COPD were included. A favorable clinical course of the exacerbation was observed
      in 92.5% of cases, with resolution of frankly purulent sputum in 99% of cases,
      associated with good tolerance. CONCLUSION: These results confirm the value of
      extended-release clarithromycin tablets as first-line treatment for presumed
      bacterial exacerbation of mild or moderately severe, stable COPD according to the
      Societe de pathologie infectieuse de langue francaise consensus.

PMID- 18722066
TI  - [Seroprevalence of Lyme Borreliosis and tick-borne encephalitis in workers at
      risk, in eastern France].
AB  - OBJECTIVE: The aim of this article was to assess the seroprevalence of Lyme
      Borreliosis and tick-borne encephalitis (TBE) among occupationally exposed forest
      workers. METHODS: Workers exposed to tick bites in Eastern France were
      interviewed by occupational health physicians of the mutualite sociale agricole
      (MSA) on their sociodemographic features, their occupational activity, their last
      tick bite, their clinical history, and their means of prevention. Blood sampling
      was carried out for antibody detection. RESULTS: Among the 2975 subjects included
      in the study, the observed seroprevalence was 14.1% for Lyme borreliosis and 3.4%
      for TBE. Age, occupational activity, and place of residence significantly
      influenced the serological status of Lyme borreliosis. The seroprevalence was
      significantly higher among woodcutters (17.5%) than among other occupational
      categories (p<.001). Seroprevalence in Alsace (26.9%) and Lorraine (16.5%) were
      significantly higher than in other regions (p<0.001 and p<0.01, respectively).
      The seroprevalence of TBE was significantly higher in Alsace (5.5%; p<0.001). The
      rates of seroprevalence for both infections varied according to forest areas. The
      multifactorial analysis of prevention practices revealed three types of behaviors
      as far as protection was concerned: "rigorous", "partial", or "insufficient".
      CONCLUSION: These results do not change the present French indications for use of
      TBE vaccine. They highlight the importance of information on these diseases and
      the need for further studies on microbial ecology and risk-factors
      identification.

PMID- 18722067
TI  - Interaction of anthracycline disaccharide with human serum albumin: investigation
      by fluorescence spectroscopic technique and modeling studies.
AB  - Anthracyclines are considered to be some of the most effective anticancer drugs
      for cancer therapy. However, drug resistance and cardiotoxicity of anthracyclines
      limit their clinical application. An 3'-azido disaccharide analogue of
      daunorubicin, 7-[4-O-(2,6-dideoxy-3-O-methyl-alpha-l-arabino-hexopyranosyl)-3
      azido-2,3,6-trideoxy-alpha-l-lyxo-hexopyranosyl]daunorubicinone (ADNR-3), was
      shown to exhibit 10-fold better activity than parent compound daunorubicin
      against the drug-resistant cells and completely overcomes the drug resistance
      with same IC(50) in both drug-resistant and drug-sensitive cells. In this paper,
      the interactions between ADNR-3 and human serum albumin (HSA) have been studied
      by spectroscopic techniques. By the analysis of fluorescence spectrum and
      fluorescence intensity, it was observed that the ADNR-3 has a strong ability to
      quench the intrinsic fluorescence of HSA through a static quenching procedure.
      The association constants of ADNR-3 with HSA were determined at different
      temperatures based on fluorescence quenching results. The negative DeltaH and
      positive DeltaS values in case of ADNR-3-HSA complexes showed that both hydrogen
      bonds and hydrophobic interactions play a role in the binding of ADNR-3 to HSA.
      Furthermore, synchronous fluorescence spectroscopy data and UV-vis absorbance
      spectra have suggested that the association between ADNR-3 and HSA changed the
      molecular conformation of HSA and the hydrophobic interactions play a major role
      in ADNR-3-HSA association. Moreover, the study of computational modeling
      indicated that ADNR-3 could bind to the site I of HSA and hydrophobic interaction
      was the major acting force for the second type of binding site, which was in
      agreement with the thermodynamic analysis. The distance, r, between donor (HSA)
      and acceptor (ADNR-3) was obtained according to the Forster's theory of non
      radiation energy transfer. In addition, the effects of common ions on the binding
      constants of ADNR-3-HSA complexes were also investigated.

PMID- 18722068
TI  - Qualitative and quantitative analysis of four species of Curcuma rhizomes using
      twice development thin layer chromatography.
AB  - The rhizomes of Curcuma phaeocaulis, Curcuma kwangsiensis, Curcuma wenyujin and
      Curcuma longa are used as Ezhu or Jianghuang in traditional Chinese medicine for
      a long time. Due to their similar morphological characters, it is difficult to
      distinguish their origins of raw materials used in clinic. In this study, a
      simple, rapid and reliable twice development TLC method was developed for
      qualitative and quantitative analysis of the four species of Curcuma rhizomes.
      The chromatography was performed on silica gel 60F(254) plate with chloroform
      methanol-formic acid (80:4:0.8, v/v/v) and petroleum ether-ethyl acetate (90:10,
      v/v) as mobile phase for twice development. The TLC markers were colorized with
      1% vanillin-H(2)SO(4) solution. The four species of Curcuma were easily
      discriminated based on their characteristic TLC profiles, and simultaneous
      quantification of eight compounds, including bisdemethoxycurcumin,
      demethoxycurcumin, curcumine, curcumenol, curcumol, curdione, furanodienone and
      curzerene, in Curcuma were also performed densitometrically at lambda(scan)=518nm
      and lambda(reference)=800 nm. The investigated compounds had good linearity
      (r(2)>0.9905) within test ranges. Therefore, the developed TLC method can be used
      for quality control of Curcuma rhizomes.

PMID- 18722069
TI  - Antibody-based enzyme-linked lectin assay (ABELLA) for the sialylated recombinant
      human erythropoietin present in culture supernatant.
AB  - The terminal sialic acid of human erythropoietin (hEPO) is essential for in vivo
      activity. The current resorcinol and HPLC methods for analyzing alpha2,3-linked
      sialic acid require more than a microgram of purified rhEPO, and purification
      takes a great deal of time and labor. In this study, we assessed the use of an
      antibody-based enzyme-linked lectin assay (ABELLA) for analyzing non-purified
      recombinant hEPO (rhEPO). The major problem of this method was the high
      background due to terminal sialylation of components of the assay (antibody and
      bovine serum albumin) other than rhEPO. To solve this problem, we used a
      monoclonal antibody (Mab 287) to capture the rhEPO, and oxidized the bovine serum
      albumin used for blocking with meta-periodate. The sialic acid content of non
      purified rhEPO measured by ABELLA was similar to that obtained by the resorcinol
      method on purified rhEPO. ABELLA has advantages such as adaptability and need for
      minimal amounts of rhEPO (40 ng/ml). Our observations suggest that ABELLA should
      reduce the time and labor needed to improve culture conditions so as to increase
      protein sialylation, and also facilitate the study of sialylation mechanisms.

PMID- 18722070
TI  - A validated, stability-indicating HPLC method for the determination of
      dexamethasone related substances on dexamethasone-coated drug-eluting stents.
AB  - An HPLC method was developed and validated to determine trace amounts of
      dexamethasone related substances on dexamethasone-coated drug-eluting stents.
      Separation of dexamethasone from its major process impurities and degradation
      products was achieved on a Zorbax Eclipse XDB C8 column using gradient elution
      and UV detection at 239 nm. The method was validated according to ICH guideline
      requirements. In addition, stent extraction efficiency, solution stability and
      method robustness were evaluated. The method was determined to be linear in the
      range of 0.01-0.30 microg ml(-1) for the quantitation of major dexamethasone
      related substances. Method accuracy was assessed by spiking dexamethasone acetate
      at three levels over the range of 0.025-0.175 microg ml(-1). The dexamethasone
      acetate recovery ranged from 89.6 to 105.8%. The intermediate precision over the
      three levels was less than 6% (n=9). The method was also shown to be repeatable
      at concentration levels of 0.025, 0.125 and 0.175 microg ml(-1) dexamethasone
      with relative standard deviation values of 4.1, 1.7 and 1.6%, respectively. The
      method was found to be specific, stability-indicating, and sensitive with a
      detection limit of 0.008 microg ml(-1) and a quantitation limit of 0.025 microg
      ml(-1) dexamethasone. Finally, the method was demonstrated to be robust,
      resistant to small variations of chromatographic variables such as pH, mobile
      phase organic/aqueous composition and column temperature. Identifying unknown
      dexamethasone degradation products in dexamethasone-coated drug-eluting stents
      was of critical interest to ensure product quality, since degradants have a
      significant impact on safety, efficacy, and product storage and handling. The
      developed chromatographic method was designed to be compatible with mass
      spectrometric detection. This paper also discusses using this chromatographic
      method coupled to an ion-trap LCQ mass spectrometer to elucidate proposed
      structures for four major dexamethasone degradants.

PMID- 18722071
TI  - A rapid lateral flow stool antigen immunoassay and (14)C-urea breath test for the
      diagnosis and eradication of Helicobacter pylori infection in children.
AB  - Our aim was to evaluate diagnostic accuracy of rapid immunochromatographic stool
      antigen test (Rapid HpSA; LINEAR Chemical, Barcelona, Spain) and a practical low
      dose (14)C urea breath test (UBT) (Heliprobetrade mark) test before and after
      eradication therapy. One hundred nine children with abdominal symptoms (age
      range, 5-17 years; mean, 12.1) underwent endoscopy, (14)C-UBT, and Rapid HpSA.
      Patients were defined as Hp infected when histology was positive for Hp. Forty
      children (36.6%) were Hp infected. The sensitivity of Rapid HpSA and (14)C-UBT
      was 65% and 92.5% (P = 0.0003), respectively; the specificity of Rapid HpSA and
      (14)C-UBT was 92.3% and 85.5% (P = 0.180), respectively. After eradication
      therapy endoscopy, (14)C-UBT and Rapid HpSA were repeated. The eradication rate
      was 70.5%. After eradication, the sensitivity of Rapid HpSA and (14)C-UBT was 60%
      and 100%, respectively; the specificity of Rapid HpSA and (14)C-UBT was 100%.
      (14)C-UBT was more reliable than the Rapid HpSA test for the diagnosis and for
      confirming eradication of Hp infection.

PMID- 18722072
TI  - Activity and DNA contamination of commercial polymerase chain reaction reagents
      for the universal 16S rDNA real-time polymerase chain reaction detection of
      bacterial pathogens in blood.
AB  - Universal 16S rRNA gene polymerase chain reaction (PCR) is a promising means of
      detecting bacteremia. Among other factors, the PCR reagents play a prominent role
      for obtaining a high sensitivity of detection. The reagents are ideally optimized
      with respect to the amplifying activity and absence of contaminating DNA. In this
      study, it was shown in a universal 16S rDNA real-time PCR assay that commercial
      PCR reagents can vary greatly among each other in these characters. Only 1 of the
      5 reagents tested met the criteria of sensitive detection of pathogen DNA with a
      minimum of false-positive results. The reagent was validated by the detection of
      pathogens at low titers using bacterial DNA extracted from blood that was spiked
      with various Gram-positive and Gram-negative bacteria.

PMID- 18722073
TI  - Presenting health risk information in different formats: the effect on
      participants' cognitive and emotional evaluation and decisions.
AB  - OBJECTIVE: Effective communication of health risks plays an important role in
      enabling patients to make adequate decisions. There is little--though
      contradictory--evidence to indicate which format is most effective for
      communicating risks, and which risk format is preferred by counselees. METHODS:
      In an experiment, subjects were presented health scenarios and risk information
      in different formats (percentages, frequencies, and population figures) and asked
      to evaluate the risks and make a decision based on these. RESULTS: Different risk
      formats had different effects on respondents' evaluation of the health risks
      presented. Contrary to our expectation, population figures were not evaluated as
      being the easiest format for all decision problems. Population figures were shown
      to have the biggest affective impact, and risks presented as population figures
      were also evaluated as significantly greater than the risks presented in other
      formats. The format of the presented risks influenced their decision in only one
      out of four decision-making situations, although in a second situation there was
      a similar trend. CONCLUSION: This study suggests that the risk format plays a
      role in the decision-making process, although it remains unclear which format is
      the most effective in terms of understanding. PRACTICE IMPLICATIONS: More
      experimental studies based on a theoretical analysis of the factors that promote
      effective risk communication are needed in the general population as well as in
      clinical settings with patients actually experiencing the risks and making the
      decisions.

PMID- 18722074
TI  - Audit and feedback using the brief Decision Support Analysis Tool (DSAT-10) to
      evaluate nurse-standardized patient encounters.
AB  - OBJECTIVE: To evaluate the brief Decision Support Analysis Tool (DSAT-10) for
      auditing the quality of nurse-standardized patient encounters, structuring
      feedback for nurses, and testing instrument reliability. METHODS: A systematic
      process was used to develop standardized patient scenarios, pilot-test scenarios,
      calibrate DSAT-10 coders, analyze taped telephone encounters using DSAT-10, and
      provide feedback. Inter-rater reliability was calculated using coder agreement,
      kappa, and intra-class correlation coefficients. RESULTS: Six scenarios portrayed
      patients' decisional uncertainty from either: pressure from others (n=2), unclear
      values (n=2), or inadequate information (n=2). Scenarios were easy to use over
      the telephone, produced realistic role performance, and were practical for audio
      recording interactions. DSAT-10 analysis of 76 nurse-standardized patient
      encounters revealed nurses' strengths (e.g., information provision) and their
      limitations (e.g., lack of discussion of values and/or support needs). Scores
      discriminated between trained and untrained nurses. The kappa coefficient over
      all items was 0.55 (95% CI: 0.49, 0.61) with higher agreement for encounters
      involving trained nurses (0.62; 95% CI: 0.43, 0.80). CONCLUSION: Auditing nurse
      standardized patient encounters using DSAT-10 and providing feedback to nurses
      was feasible. Although DSAT-10 items had adequate inter-rater reliability and
      discriminated between trained/untrained nurses, some items were problematic.
      PRACTICE IMPLICATIONS: Providing feedback on nurse encounters with standardized
      patients experiencing uncertainty has the potential to enhance nurses' decision
      support skills.

PMID- 18722076
TI  - Long-term survival after combined modality treatment in metastatic bladder cancer
      patients presenting with supra-regional tumor positive lymph nodes only.
AB  - AIMS: To evaluate if combined treatment should be offered to bladder cancer
      patients presenting with supra-regional lymph node metastases only and a clinical
      complete or partial response after chemotherapy. PATIENTS AND METHODS: We
      identified 14 patients with supra-regional lymph node metastases out of 394
      patients with transitional cell carcinoma (TCC) treated in our institute with
      cystectomy and regional and supra-regional lymph node dissection between 1987 and
      2007. Prior to cystectomy, neoadjuvant chemotherapy had been given. The patients
      received a total of four cycles of platinum-based chemotherapy. RESULTS: Five
      patients had a CR, nine patients had a PR after neoadjuvant chemotherapy.
      Histopathological proof of complete response in the bladder was confirmed in all
      five cases. One of these five patients had a CR in the bladder but pelvic lymph
      nodes still contained vital tumor. Five patients had no tumor in the lymph nodes,
      whereas four had tumor in the lymph nodes. Eleven patients died due to bladder
      cancer, seven of them within 1 year after cystectomy. The 3- and 5-year disease
      specific survival rates were 36% (95% CI: 10-60%) and 24% (95% CI: 0-49%). Mean
      follow-up was 2.5 years. CONCLUSIONS: Combination therapy consisting of
      neoadjuvant chemotherapy and surgery in selected patients with tumor positive
      supra-regional lymph nodes only can result in durable long-term survival rates
      (24% 5-year survival). Response evaluation after neoadjuvant chemotherapy might
      play a decisive role in the selection of patients undergoing subsequent surgical
      removal of all known tumor sites.

PMID- 18722075
TI  - Adapting Washington Circle performance measures for public sector substance abuse
      treatment systems.
AB  - The Washington Circle, a group focused on developing and disseminating
      performance measures for substance abuse services, developed three such measures
      for private health plans. In this article, we explore whether these measures are
      appropriate for meeting measurement goals in the public sector and feasible to
      calculate in the public sector using data collected for administrative purposes
      by state and local substance abuse and/or mental health agencies. Working
      collaboratively, 12 states specified revised measures and 6 states pilot tested
      them. Two measures were retained from the original specifications: initiation of
      treatment and treatment engagement. Additional measures were focused on
      continuity of care after assessment, detoxification, residential or inpatient
      care. These data demonstrate that state agencies can calculate performance
      measures from routinely available information and that there is wide variability
      in these indicators. Ongoing research is needed to examine the reasons for these
      results, which might include lack of patient interest or commitment, need for
      quality improvement efforts, or financial issues.

PMID- 18722077
TI  - Hurthle cell carcinoma of the thyroid: Retrospective review of 62 patients
      treated at the Royal Marsden Hospital between 1946 and 2003.
AB  - INTRODUCTION: Previous studies have included Hurthle cell carcinoma (HCC) as a
      variant of follicular thyroid carcinoma in analysis of clinical outcome and
      others have failed to adequately distinguish between benign and malignant Hurthle
      cell neoplasms. The aim of this study was to report our experience of
      histologically confirmed malignant HCC, identifying patient, tumour and treatment
      factors that predict outcome. METHODS: A retrospective review was undertaken of
      all patients treated with HCC between 1946 and 2003. Study end-points were
      disease-free survival (DFS) and cause-specific survival (CSS). Demographic,
      pathological and treatment-related factors were all correlated with the study end
      points. RESULTS: Sixty-two patients were followed up for a median (range) of 58
      months (2-629). On multivariate analysis, only extent of surgery (p<0.001) was an
      independent factor affecting CSS. Lymph node status (p=0.008), presence of
      metastases at diagnosis (p=0.005) and tumour stage (p=0.009) were independent
      predictors of DFS. CONCLUSIONS: HCC appears to be a separate entity from
      follicular thyroid carcinoma (FTC), with a more aggressive disease profile. Lymph
      node status, tumour stage, and the presence of metastases are independent
      predictors of DFS. Radical surgery may improve outcome in HCC.

PMID- 18722078
TI  - The role of APC and beta-catenin in the aetiology of aggressive fibromatosis
      (desmoid tumors).
AB  - BACKGROUND: Aggressive fibromatosis (syn. desmoid tumor) is a sporadically
      occurring neoplastic proliferation of fibroblasts originating from
      musculoaponeurotic planes, forming invasively growing masses without the
      capability to metastasize. The choice of treatment remains surgical resection
      with or without radiotherapy, and is characterized by high recurrence rates.
      Better understanding of the aetiology of aggressive fibromatosis is needed to be
      able to develop new treatment strategies to cope with the high recurrence rates.
      METHODS: Relevant studies were identified through a search of the electronic
      databases PubMed/ Medline. The following search terms were used: 'aggressive
      fibromatosis', 'desmoid tumor', 'adenomatous polyposis coli', 'APC', 'beta
      catenin', 'Wnt', 'Wingless' and 'Wnt/Wingless'. Studies were selected for review
      on the basis of abstract reading. A hand search was performed by checking
      reference lists in selected articles. RESULTS: The neoplastic nature of
      aggressive fibromatosis and the role of the adenomatous polyposis coli (APC) and
      beta-catenin signaling cascade in driving the onset and progression of this
      disease are discussed. CONCLUSION: Mutations in either the APC or beta-catenin
      genes are likely to be a major driving force in the formation of these desmoid
      tumors. More research is needed to develop new treatment strategies.

PMID- 18722079
TI  - [A national survey of postoperative pain management in France: influence of type
      of surgical centres].
AB  - BACKGROUND: The French Society of Anaesthesia and Intensive Care has supported a
      national survey of postoperative pain (POP) management in various type of
      surgical centres. METHODOLOGY: The survey was cross-checking data on information,
      evaluation, treatment concerning POP of adult patient within 24h after surgery in
      surgical centres randomly selected according to teaching status, public or
      private funding and size. A local anaesthetist referent provided information on
      management of POP. RESULTS: One thousand and nine hundred adult patients were
      audited. Information on POP was better understood in private centres. Rarely
      prescribed, written evaluation of POP was frequent on the ward (>90%) without any
      difference between centres. In all centres, POP evaluation tool were by
      decreasing frequency, numerical scale, nonspecific tool, visual analog scale and
      verbal scale. In all institutions, pain was rarely a criterion for recovery room
      discharge. Reported POP was mild at rest, moderate when moving and intense for
      maximal pain with no difference between centres. Incidence of side-effects was
      similar in all centres according to patient or chart, with mainly nausea and
      vomiting. Analgesics were frequently started during anaesthesia. Patient
      controlled analgesia was used less frequently than subcutaneous morphine whose
      prescription frequently did not follow guidelines especially in small hospital.
      Non opioid analgesic included paracetamol, ketoprofen mainly in private structure
      and nefopam mainly in university hospital. Epidural or peripheral nerve blocks
      were underused similarly in all centres. Evaluation or treatment protocols were
      less frequent in university hospital. CONCLUSION: This national, prospective,
      patient-based, observational survey reveals similar achievements in different
      surgical centres but also some differences and persistent challenges for POP
      management.

PMID- 18722080
TI  - [A "very special" edition].

PMID- 18722081
TI  - [The French did dit!].

PMID- 18722082
TI  - [Recurrent systemic embolism: look for a thrombus in... the thoracic aorta].
AB  - Thoracic aortic mural thrombus is a rare entity and potential source of serious
      systemic emboli. The progress of computed tomography (CT) angiography and the
      current use of transesophageal echocardiography (TEE) after any embolic event
      have considerably increased the frequency of diagnostic and there is a growing
      interest about the etiopathogenesis, which is still widely misunderstood.
      Therapeutic management remains controversial. We present a case of floating
      thrombus in the thoracic aorta detected by contrast-enhanced CT scan. This
      thrombus was responsible for two close major embolic events and was therefore
      managed surgically. Finally, outcome was favorable.

PMID- 18722083
TI  - [The French Society of Anesthesia and Recovery in 2008 or the story of pride].

PMID- 18722084
TI  - Shared priorities for the end-of-life period.
AB  - This study investigated end-of-life priorities of terminally ill patients and
      their intimate associates. A primary goal was to reduce the number of items in an
      existing instrument measuring survivors' evaluations of the quality of dying and
      death. Three Seattle-area patient samples (chronic obstructive pulmonary disease
      patients, hospice patients, and participants in an efficacy trial of
      complementary comfort care) and their significant others provided priority
      rankings of 26 experiences at end of life. Two items represented top priorities
      for all subgroups: time with family/friends and pain control. Clustered
      multivariate probit regression models suggested only a few significant
      differences between participant groups in priority rankings: higher education
      increased the priority placed on having available means to hasten death, cancer
      patients and persons in the hospice sample (likely those experiencing
      disproportionate pain) assigned pain control higher priority than other groups,
      persons in the clinical trial (which included massage as an intervention)
      assigned higher priority to human touch, and racial/ethnic minorities emphasized
      the importance of having funeral arrangements made. In the clinical trial sample
      (the most recently interviewed), the importance attributed to taking care of
      health care costs increased over time. If researchers were to use a reduced set
      of the 17 items mentioned among the top five priorities by at least 10% of the
      sample, none of the items that varied significantly between subgroups or over
      time would be eliminated. This change would reduce respondent burden in future
      investigations, simplify analyses aimed at identifying domains underlying the
      dying-and-death experience, and exclude the top-priority item of fewer than 4% of
      respondents.

PMID- 18722085
TI  - Using different perspectives to generate items for a new scale measuring medical
      outcomes of dysphagia (MOD).
AB  - OBJECTIVE: To compare and contrast clinician, patient, and caregiver perspectives
      to generate all important and salient items for a new scale to measure medical
      consequences relevant to adult patients with dysphagia. STUDY DESIGN AND SETTING:
      Six focus groups (three with clinicians, two with patients, and one with
      caregivers) were conducted with a total of 33 participants. Through the constant
      comparison method of Grounded Theory, analysis began with open coding and
      progressed with higher-order categorization to derive perceptions from differing
      vantage points. RESULTS: Three themes evolved: (1) clinicians, caregivers, and
      patients each limited the medical consequences of dysphagia to the same
      impairment domains: pulmonary, nutritional, and psychological; (2) these
      consequences were given the same priority by clinicians and caregivers, but
      patients ranked them differently; (3) within each impairment domain, few
      dimensions were derived by clinicians and many by patients. Patients were more
      elaborate in their descriptions of psychological consequences. CONCLUSIONS: The
      use of qualitative methodology to generate different perspectives derived
      different content. Clinicians, caregivers, and patients all agreed on the
      importance of three domains but differed in their prioritization and specific
      issues. These findings provide the necessary foundation for development of a
      comprehensive tool to measure medical consequences among patients with dysphagia.

PMID- 18722086
TI  - The fidelity of treatment delivery can be assessed in treatment outcome studies:
      a successful illustration from behavioral medicine.
AB  - OBJECTIVES: Treatment outcome studies ought to assess the fidelity of their
      treatments, including treatment delivery, but practical guidelines and examples
      for this are lacking. Based on general recommendations in available literature,
      this study proposes and illustrates the design and application of a Method of
      Assessing Treatment Delivery (MATD) in a behavioral medicine trial comparing two
      treatments for chronic low back pain. STUDY DESIGN AND SETTING: In designing
      MATD, two experts identified several feasible treatment elements. Agreement
      between the experts in classifying these elements into five categories (essential
      and unique, essential but not unique, unique but not essential, compatible,
      prohibited) was assessed. In applying MATD, treatment recordings were evaluated
      by two independent raters, who coded the (non)-occurrence of MATD elements and
      who categorized each session as belonging to one of the two treatments. RESULTS:
      MATDs content validity was supported by adequate agreement between the experts'
      classifications of the treatment elements. MATDs interrater reliability was good.
      CONCLUSION: Comprehensive illustrations of designing and applying MATD may
      encourage the verification of treatment delivery as a partial reflection of
      treatment fidelity in forthcoming treatment outcome studies.

PMID- 18722087
TI  - Predictive values of acute coronary syndrome discharge diagnoses differed in the
      Danish National Patient Registry.
AB  - OBJECTIVE: To investigate the predictive value of acute coronary syndrome (ACS)
      diagnoses, including unstable angina pectoris, myocardial infarction, and cardiac
      arrest, in the Danish National Patient Registry. STUDY DESIGN AND SETTING: We
      identified all first-time ACS diagnoses in the Danish National Patient Registry
      among participants in the Danish cohort study "Diet, Cancer and Health" through
      the end of 2003. We retrieved and reviewed medical records based on current
      European Society of Cardiology criteria for ACS. RESULTS: We reviewed hospital
      medical records of 1,577 out of 1,654 patients (95.3%) who had been hospitalized
      with a first-time ACS diagnosis. The overall positive predictive value for ACS
      was 65.5% (95% confidence interval [CI]=63.1-67.9%). Stratification by sub
      diagnosis and hospital department produced significantly higher positive
      predictive values for myocardial infarction diagnoses (81.9%; 95% CI=79.5-84.2%)
      and among patients who received an ACS diagnosis in a ward (80.1%; 95% CI=77.7
      82.3%). CONCLUSION: The ACS diagnoses contained in hospital discharge registries
      should be used with caution. If validation is not possible, restricting analyses
      to patients with myocardial infarction and/or patients discharged from wards
      might be a useful alternative.

PMID- 18722088
TI  - The capture-mark-recapture technique can be used as a stopping rule when
      searching in systematic reviews.
AB  - OBJECTIVE: Researchers have no empirically based search stopping rule when
      looking for potentially relevant articles for inclusion in systematic reviews. We
      tested a stopping strategy based on capture-mark-recapture (CMR; i.e., the
      Horizon Estimate) statistical modeling to estimate the total number of articles
      in the domain of clinical decision support tools for osteoporosis disease
      management using four large bibliographic databases (Medline, EMBASE, CINAHL, and
      EBM reviews). STUDY DESIGN AND SETTING: Retrospective evaluation of the Horizon
      Estimate using a systematic review of randomized controlled trials (RCTs) at two
      levels of article screening: title and abstract (1,246 potentially relevant
      articles) and full text (42 potentially relevant articles). RESULTS: The CMR
      model suggests that the total number of potential articles was 1,838 for the
      first level of screening, and 49 for the full-text level. The four databases
      provided 68% of known articles for the first level of screening and 81% for full
      text screening. CONCLUSIONS: The CMR technique can be used in systematic reviews
      to estimate the closeness to capturing the total body of literature on a given
      topic. More studies are needed to objectively determine the usefulness of Horizon
      Estimates as a stopping rule strategy for systematic review searching.

PMID- 18722089
TI  - Valued life activity disability played a significant role in self-rated health
      among adults with chronic health conditions.
AB  - OBJECTIVE: Because self-rated health (SRH) is strongly associated with health
      outcomes, it is important to identify factors that individuals take into account
      when they assess their health. We examined the role of valued life activities
      (VLAs), the wide range of activities deemed to be important to individuals, in
      SRH assessments. STUDY DESIGN AND SETTING: Data were from three cohort studies of
      individuals with different chronic conditions--rheumatoid arthritis (RA),
      systemic lupus erythematosus (SLE), and chronic obstructive pulmonary disease
      (COPD). Each cohort's data were collected through structured telephone
      interviews. Logistic regression analyses identified factors associated with
      ratings of fair/poor SRH. All analyses included sociodemographic characteristics,
      general and disease-specific health-related factors, and general measures of
      physical functioning. RESULTS: Substantial portions of each group rated their
      health as fair/poor (RA 37%, SLE 47%, COPD 40%). In each group, VLA disability
      was strongly associated with fair/poor health (RA: OR=4.44 [1.86,10.62]; SLE:
      OR=3.60 [2.10,6.16]; COPD: OR=2.76 [1.30,5.85]), even after accounting for
      covariates. CONCLUSION: VLA disability appears to play a substantial role in
      individual perceptions of health, over and above other measures of health status,
      disease symptoms, and general physical functioning.

PMID- 18722090
TI  - Among older adults, the responsiveness of self-rated health to changes in
      Charlson comorbidity was moderated by age and baseline comorbidity.
AB  - OBJECTIVE: To examine the impact of changes in comorbidity--as measured by the
      Charlson comorbidity index--on self-rated health in a large sample of community
      dwelling elderly over a 1-year period, and to examine the differential effects of
      changes in specific Charlson diagnostic categories. STUDY DESIGN AND SETTING:
      Longitudinal survey data on self-rated health were linked with Medicare
      inpatient, outpatient, and physician visit data for 30,535 U.S. elderly residing
      in Pennsylvania. Multivariate logistic regression with fractional polynomials was
      used to model relationships involving baseline and changing Charlson comorbidity
      with self-rated health decline, and to evaluate covariate interactions. RESULTS:
      Comorbidity change was associated with greater likelihood of worsened self-rated
      health, but the relationship was nonlinear and was moderated by age and baseline
      comorbidity. The impact of comorbidity change appeared to be less among older
      individuals and those with higher baseline comorbidity. Declines in self-rated
      health were most likely following new diagnoses for metastatic tumors, paralysis,
      and dementia. CONCLUSION: Self-rated health is responsive to changes in Charlson
      comorbidity, but nonlinearity and interactions suggest complexity in how elderly
      respond to comorbidity change. Younger individuals and those with initially low
      comorbidity are more likely to reduce self-ratings of health following new
      diagnoses for chronic conditions.

PMID- 18722091
TI  - Combined surgery and postoperative radiotherapy for oropharyngeal squamous cell
      carcinoma in Korea: analysis of 110 cases.
AB  - The treatment of oropharyngeal squamous cell carcinoma (OSCC) remains
      controversial. This study reviews the authors' experience of treating OSCC,
      evaluates the oncologic outcome and assesses the factors affecting local/regional
      recurrence. A retrospective analysis of 110 consecutive OSCC patients treated
      primarily by surgery and/or postoperative radiotherapy was carried out. 82% of
      patients had advanced disease (stage III or IV). The 5-year overall survival and
      disease specific survival rates (DSSR) were 58% and 65%, respectively. The DSSR
      of the soft palate or posterior pharyngeal wall, tonsillar area, and base of
      tongue were 80%, 62%, and 51%, respectively (P<0.05). The 5-year DSSR according
      to the American Joint Committee on Cancer stages was 94% for early stage and 56%
      for advanced stage (P<0.05). The overall recurrence rate was 38% (42 patients).
      The most frequent site of recurrence was the neck (46%). Only 14% of patients
      with recurrences were treated successfully. Positive resection margins and the
      presence of pathologic lymph nodes influenced the recurrence at the primary
      lesion and in the neck, respectively, in a statistically significant manner.
      Surgery and postoperative radiotherapy provided a superior outcome in patients
      with advanced OSCC. A randomized study is required to assess the oncologic and
      functional superiority of surgery or chemoradiation.

PMID- 18722092
TI  - Social cognition as a mediator of cognition and outcome among deaf and hearing
      people with schizophrenia.
AB  - It has been suggested in the research literature that facial affect processing
      (FAP) and theory of mind (ToM) are both potential mediators of the well
      established relationship between cognition and functional outcome among people
      with schizophrenia. The current project tests the mediating potency of these two
      domains of social cognition among deaf and hearing people with schizophrenia.
      Sixty-five people (34 deaf, 31 hearing) were assessed using measures of verbal
      and visual memory, attention, visual processing, FAP, and ToM. The results
      suggest that each domain of cognition, save vigilance, exerts an effect on
      functional outcome indirectly through its influence on social cognition. The
      patterns of mediation varied when the samples were broken down by hearing status
      and analyzed separately. Namely, the cognitive tasks directly involving
      linguistic ability (early visual processing [EVP] and word memory) were best
      mediated by social cognition for hearing subjects. For deaf subjects, the
      nonlinguistic cognitive tasks (e.g., visual-spatial memory-recall and copy [VSM
      recall and VSM-copy]) were best mediated by social cognition. While FAP and ToM
      were equally effective as mediators for hearing subjects, FAP was a more potent
      mediator than ToM for deaf subjects. This study extends prior work in the area of
      social cognition and schizophrenia and indicates that the development of
      cognitive rehabilitation strategies should include not only interventions
      targeting specific cognitive abilities, such as attention and memory, but should
      include an emphasis on social-cognitive domains, including FAP and ToM. Further,
      deaf and hearing subjects may benefit from interventions addressing aspects of
      cognition that support linguistic ability, especially as they relate to social
      cognition.

PMID- 18722093
TI  - Endothelin signaling axis activates osteopontin expression through PI3 kinase
      pathway in A375 melanoma cells.

PMID- 18722094
TI  - [The danger of small height. Does a lower height become pathological in our
      society?].

PMID- 18722095
TI  - Are behavioural approaches feasible and effective in the treatment of type 2
      diabetes? A propensity score analysis vs. prescriptive diet.
AB  - BACKGROUND AND AIMS: Lifestyle changes are considered first line treatment in
      type 2 diabetes, but very few data are available in the "real world" of diabetes
      units. We aimed to measure the effectiveness of moderate and high intensity
      interventions on weight loss, metabolic control and insulin use. We report a
      prospective cohort study, carried out in 822 consecutive subjects with type 2
      diabetes, first seen in a 4-year period in a diabetes unit of an academy
      hospital. METHODS AND RESULTS: Subjects were treated with either a sole
      prescriptive diet (Diet), or received an additional short-course Elementary
      Nutritional Education (4 group sessions-ENE) or an intensive Cognitive
      Behavioural Therapy (12-15 group sessions-CBT). The results were adjusted for the
      propensity score to be assigned different treatments, derived from logistic
      regression on the basis of age, gender, BMI, HbA1c, diabetes duration and insulin
      use at baseline. Main outcome measures were weight loss and weight loss
      maintenance, metabolic control, and secondary failure to insulin use. Both
      structured programmes produced a larger weight loss, and the adjusted probability
      of achieving the 7% weight loss target was increased. Similarly, both programmes
      favoured metabolic control, irrespective of insulin use. After adjustment for
      propensity score, both ENE (hazard ratio, 0.48; 95% CI, 0.27-0.84) and CBT
      (hazard ratio, 0.36; 95% CI, 0.16-0.83) were associated with a reduced risk of de
      novo insulin treatment. CONCLUSION: Structured behavioural programmes aimed at
      lifestyle changes are feasible and effective in the "real world" setting of a
      diabetes unit for the treatment of type 2 diabetes.

PMID- 18722096
TI  - Dietary patterns and 5-year incidence of cardiovascular disease: a multivariate
      analysis of the ATTICA study.
AB  - BACKGROUND AND AIMS: The 5-year incidence of cardiovascular disease (CVD) in
      relation to dietary habits, among men and women from Greece, was evaluated.
      METHODS AND RESULTS: From May 2001 to December 2002, 1514 men and 1528 women (>18
      years) without any clinical evidence of CVD, living in the Attica area, Greece,
      were enrolled in the ATTICA study. In 2006, a group of experts performed the 5
      year follow-up (941 of the 3042 participants were lost). Development of CVD
      (coronary heart disease, acute coronary syndromes, stroke, or other CVD) during
      the follow-up period was defined according to WHO ICD-10 criteria. Principal
      components analysis was applied, and 15 dietary patterns were extracted (71% of
      total information explained) from 26 foods or food groups. The 5-year incidence
      of CVD was 11.0% in men and 6.1% in women (p<0.001); the case fatality rate was
      1.6%. Multi-adjusted analysis revealed that the dietary pattern that was mainly
      characterized by cereals, small fish, hardtack and olive oil intake, was
      associated with lower CVD risk (HR per 1 unit=0.72, 95% CI 0.52-1.00); the
      pattern that was characterized by fruits, vegetables intake and olive oil use in
      daily cooking was associated with lower CVD risk (HR per 1 unit=0.80, 95% CI 0.66
      0.97); while patterns that were mainly characterized by sweets, red meat,
      margarine, salty nuts intake, and hard cheese, as well as alcohol intake, were
      associated with higher CVD risk (HR per 1 unit=1.26, 95% CI 1.01-1.56, and HR per
      1 unit=1.32, 95% CI 1.05-1.66, respectively). CONCLUSIONS: Multivariate
      statistical methods revealed dietary patterns based on empirical epidemiological
      data which were associated with the development of CVD.

PMID- 18722097
TI  - A TSP-1 functional fragment inhibits activation of latent transforming growth
      factor-beta1 derived from rat alveolar macrophage after bleomycin treatment.
AB  - The antineoplastic antibiotic, bleomycin, is known to induce a well-recognized
      model of lung fibrosis. Active transforming growth factor-beta1 (TGF-beta1) plays
      a key role in lung fibrosis induced by bleomycin, TSP-1 (thrombospondin-1) being
      critical to the activation of L (latent)-TGF-beta1 by virtue of an association of
      the TSP-1/L-TGF-beta1 complex with CD36, involving the sequence CSVTCG of the TSP
      1 functional fragment. To observe the inhibitory effects of TSP-1 functional
      fragments, critical for CD36 binding, on the activation of L-TGF-beta1, we
      isolated alveolar macrophages from Wistar rat lungs 7 days after bleomycin
      administration (5mg/kg body weight) and cultured the cells with or without TSP-1
      functional or control fragments. We observed a cell surface association of TGF
      beta1 with CD36 by immunofluorescence and quantified the active and total TGF
      beta1 by ELISA. The co-localization of CD36 with TGF-beta1, shown by a yellow
      fluorescence deriving from a mixture of the green and red of the two components,
      for the TSP-1 functional fragment groups was clearly less than that of the TSP-1
      control fragment groups. The quantities and the percentages of active TGF-beta1
      in the TSP-1 functional fragment groups were lower than those in the TSP-1
      control fragment groups (P<0.05 or P<0.01). These findings suggest that TSP-1
      functional fragments could inhibit the activation of L-TGF-beta1 secreted by
      activated alveolar macrophages through blocking the binding of TSP-1 to CD36.

PMID- 18722098
TI  - Reduced cell number in the neocortical part of the human fetal brain in Down
      syndrome.
AB  - Mental retardation is seen in all individuals with Down syndrome (DS) and
      different brain abnormalities are reported. The aim of this study was to
      investigate if mental retardation at least in part is a result of a lower cell
      number in the neocortical part of the human fetal forebrain. We therefore
      compared brains of DS fetuses aged 19 weeks of gestation with normal control
      brains. The cell numbers were estimated using the optical fractionator method.
      The total cell number in the neocortical part of four DS human fetal forebrain
      was found to be substantially smaller in DS compared to the normal fetus. The
      average total cell number of 6.85 billion was equal to a reduction by 34%
      compared to the 10.4 billion cells in a normal fetal brain of that age. This
      study indicates that the mental retardation found in DS is based on a structural
      deficit in the human fetal brain already present in the second trimester.

PMID- 18722099
TI  - Nebrodeolysin, a novel hemolytic protein from mushroom Pleurotus nebrodensis with
      apoptosis-inducing and anti-HIV-1 effects.
AB  - A novel hemolysin was isolated from the edible mushroom Pleurotus nebrodensis by
      ion exchange and gel filtration chromatography on DEAE-Sepharose and Sephacryl S
      100. The hemolysin from Pleurotus nebrodensis hemolysin (nebrodeolysin) is a
      monomeric protein with a molecular weight of approximately 27 kDa as determined
      by gel filtration and SDS-PAGE. Nebrodeolysin exhibited remarkable hemolytic
      activity towards rabbit erythrocytes and caused efflux of potassium ions from
      erythrocytes. Subsequently, this hemolysin showed strong cytotoxicity against Lu
      04, Bre-04, HepG2, L929, and HeLa cells. It was also found that this hemolysin
      induced apoptosis in L929 and HeLa cells as evidenced by microscopic observations
      and DNA ladder, respectively. Moreover, this hemolysin was shown to possess anti
      HIV-1 activity in CEM cell culture.

PMID- 18722100
TI  - Non-reversible airway obstruction in never smokers: results from the Austrian
      BOLD study.
AB  - BACKGROUND: The presence of non-reversible airway obstruction (AO) in never
      smokers has only received limited attention until now. METHODS: We analyzed data
      from the Austrian Burden of Obstructive Lung Disease (BOLD) study. We defined non
      reversible AO as post-bronchodilator FEV(1)/FVC <0.7 which corresponds to COPD I
      and higher (COPD I+) according to current GOLD guidelines. Significant AO was
      defined as FEV(1)/FVC <0.7 and FEV(1) <80% predicted (GOLD II and higher, GOLD
      II+). The prevalence and characteristics of non-reversible AO in never smokers
      were analyzed in relation to the severity of the disease. RESULTS: Never smokers
      comprised 47.3% of the study population. Non-reversible AO was seen in 18.2% of
      never smokers, and 5.5% of never smokers fulfilled criteria for significant non
      reversible AO (GOLD stage II+). Therefore, the resulting population prevalence of
      significant non-reversible AO (GOLD stage II+) was 2.6%. Never smokers with non
      reversible AO were predominantly female and slightly older. The airway
      obstruction was found to be less severe as compared with ever smokers. Despite
      this, 20% of never smokers with significant non-reversible AO (GOLD stage II+)
      reported respiratory symptoms and 50% reported impairment of quality of life.
      This burden of illness in never smokers was similar to that in smokers when
      severity of AO was taken into account. CONCLUSION: Approximately every third
      subject with non-reversible AO has never smoked, yet still demonstrates a
      substantial burden of symptoms and impairment of quality of life. Never smokers
      should receive far greater attention when efforts are undertaken to prevent and
      treat chronic airway obstruction.

PMID- 18722101
TI  - Screening for alpha1-antitrypsin deficiency in Lithuanian patients with COPD.
AB  - BACKGROUND: Alpha1-antitrypsin (AAT) deficiency is an under-diagnosed condition
      in patients with chronic obstructive pulmonary disease (COPD). The objective of
      the present screening was to estimate the AAT gene frequency and prevalence and
      to identify AAT deficiency cases in a large cohort of Lithuanian patients with
      COPD. METHODS: A nationwide program of AAT deficiency was conducted in 1167 COPD
      patients, defined according to the GOLD criteria. Patients were collected from
      outpatient clinics in five different Lithuanian regions (Kaunas, Vilnius,
      Siauliai, Klaipeda and Alytus). AAT serum concentrations were measured by
      nephelometry; PI-phenotypes characterized by isoelectric-focusing. RESULTS: Mean
      age and FEV(1) were 62.0 (10.3) and 54.7% (10.9), respectively. Ninety-one AAT
      deficiency genotypes (40 MZ, 39 MS, 1 SS, 3 SZ and 8 ZZ) were identified.
      Calculated PI(*)S and PI(*)Z frequencies, expressed in per 1000, were 18.8 (95%
      CI: 13.9-25) and 25.3 (95% CI: 19.4-32.7), respectively. The calculated AAT gene
      prevalence (Hardy-Weinberg principle) was: 1/1.09 for MM, 1/28 for MS, 1/2814 for
      SS, 1/20 for MZ, 1/1049 for SZ and 1/1565 for ZZ. Calculated Odds ratio (OR) for
      PI(*)Z in COPD vs. Lithuanian healthy people was of 1.87 (P=0.004). CONCLUSION:
      The OR for each genotypic class demonstrated a significant increase of MZ, SZ and
      ZZ genotypes in COPD patients. The results of the present study, with a
      significant number of ZZ individuals detected, support the general concept of
      targeted screening for AAT deficiency in countries like Lithuania, with a large
      population of COPD patients and low awareness among care-givers about this
      genetic condition.

PMID- 18722102
TI  - On-chip ligation of multiplexing probe-pairs for identifying point mutations out
      of dense SNP loci.
AB  - Detailed analyses of dense single nucleotide polymorphism (SNP) loci within
      rifampin-resistance determining region (RRDR) are very important for the early
      assessment of drug resistance of Mycobacterium tuberculosis. A strategy was
      developed here to specifically identify point mutations out of dense SNP loci by
      on-chip ligation of multiplexing probe-pairs (MPPs). A probe-pair combines a
      common probe with a discriminating probe which is covalently attached to a DNA
      chip. The common probe hybridizes to the discriminating probe via a unique "zip
      code complement". The allele-specific part on the 3'-end of the discriminating
      probe becomes covalently ligated to the adjacent part on the 5'-end of the common
      probe if and only if a mutation is present. Thus upon zip-code recognition, the
      process of identifying a mutation of interest is entirely located into
      corresponding well on the chip. As a consequence, cross-reactions and biased
      competitive attachments to targets, both of which result from the presence of
      various multiplexing probes, are greatly minimized. Mutation detection was
      performed by direct visualization using enzyme-linked assay. The method was
      demonstrated with an initial set of 24 probe-pairs targeting 22 clinically
      meaningful mutations within an 81-bp RRDR. 130-bp fragments of the rpoB gene from
      15 clinical isolates were identified and were in 100% agreement with results from
      independent sequencing.

PMID- 18722103
TI  - Direct electrochemistry of hemoglobin on carbonized titania nanotubes and its
      application in a sensitive reagentless hydrogen peroxide biosensor.
AB  - Carbonized TiO(2) nanotubes (TNT/C) prepared by carbonization with organic
      polymers possess advantages combined from high conductivity of carbon and
      nanostructure of TiO(2) nanotubes. The material was used as a supporting matrix
      to immobilize a redox protein, hemoglobin (Hb), to explore its direct electron
      transfer ability. The apparent heterogeneous electron transfer rate constant
      (k(ET)) of Hb on TNT/C is 108s(-1), which is much higher than that in the
      reported works, demonstrating excellent direct electrochemistry behavior. The
      TNT/C-Hb modified glassy carbon electrode (GCE) demonstrates significant
      electrocatalytic activity for reduction of hydrogen peroxide with a small
      apparent Michaelis-Menten constant (87.5 microM). The TNT/C-Hb based H(2)O(2)
      sensor has a low detection limit (0.92 microM), fast response time (3s) and high
      dynamic response range (10(-6) to 10(-4)M), a much better performance than the
      reported works. These results demonstrate that a direct electrochemistry behavior
      can be significantly enhanced through simple carbon coating on a nanostructured
      material for higher reaction surface area and better conductivity. This work
      suggests that Hb-immobilized TNT/C has potential applications in a sensitive
      H(2)O(2) sensor.

PMID- 18722105
TI  - Multidepth screening of living cells using optical waveguides.
AB  - The use of planar optical waveguides as substrata for label-free, non-invasive
      monitoring of cells growing on them is demonstrated. Different submicrometre
      depths (measured from and perpendicular to the substratum surface) can be
      selected for monitoring. The so-called symmetry waveguide configuration with a
      low refractive index waveguide support (nanoporous silica with refractive index
      approximately 1.2) and a polystyrene waveguiding film with a heat-embossed
      grating coupler is exploited to obtain practically useful differences between the
      penetration depths of different waveguide modes. Robust data processing
      techniques are developed to obtain quantitative information about the cell
      refractive index profile perpendicular to the substratum from the measured
      effective refractive indices of the modes. In particular, a method is introduced
      with which cell refractive index variations above and below a predefined and
      tunable depth can be separated using two modes. The technique can be extended to
      more modes to gain even more comprehensive information from predefined
      submicrometre slices of the cell layer. The introduced methods are also suitable
      for monitoring the kinetics of changes in cell refractive index profiles.

PMID- 18722104
TI  - Monitoring of hormonal drug effect in a single breast cancer cell using an
      estrogen responsive GFP reporter vector delivered by a nanoneedle.
AB  - In this study, we have evaluated a sensor system for a hormonal drug effect in a
      single cell level using a novel low invasive single cell DNA delivery technology
      using a nanoneedle. An estrogen responsive GFP reporter vector (pEREGFP9) was
      constructed and its estrogenic response activity was confirmed in breast cancer
      cells (MCF-7) using lipofection as the means of transferring the vector to the
      cells. The pEREGFP9 vector was delivered to a single MCF-7 using a nanoneedle and
      the effect of ICI 182,780, which is an antagonist of estrogen, was observed using
      the GFP expression level. By ICI 182,780 treatment, the fluorescence intensity of
      the GFP was decreased by 30-50% within 24h. This technology is the very first
      trial of single cell diagnosis and we are looking forward to applying it to
      precious single cell diagnosis in medical fields.

PMID- 18722106
TI  - Maternal resuscitation: plenty of room for improvement.

PMID- 18722107
TI  - p16 methylation does not affect protein expression in cervical carcinogenesis.
AB  - Previous studies have reported a frequency range of 19-61% for p16 methylation in
      cervical cancers. However, p16 is strongly expressed in over 90% of cervical
      cancers and pre-cancers, due to interactions of HPV oncogenes with p53 and pRb.
      In order to clarify these controversial findings, we developed a new bisulphite
      sequencing protocol to determine the methylation status of p16. DNA extracted
      from 17 cell lines and 94 microdissected clinical samples was subjected to
      methylation analysis. p16 expression was confirmed in Western blot and
      immunohistochemistry. Complete methylation of p16 was found in none of the
      dysplastic lesions, but in 26% of the cervical carcinomas. However,
      immunohistochemistry showed strong p16 expression in all cancers. These findings
      indicate that p16 methylation does not implicate loss of p16 expression in HPV
      induced tumours. In cervical cancer, methylation of p16 does not seem to be an
      underlying pathogenic mechanism, but may be a result of increasing genetic and
      epigenetic instability.

PMID- 18722108
TI  - Expression of integrin-linked kinase and its binding partners in chondrosarcoma:
      association with prognostic significance.
AB  - Integrin-linked kinase (ILK) and its binding partners alpha-parvin, beta-parvin,
      Mig-2 and Migfilin are important components of the cell-matrix adhesions
      implicated in cell motility, growth, survival and ultimately carcinogenesis.
      Herein, we investigated immunohistochemically the expression of these molecules
      in cartilaginous neoplasms and explored their involvement in chondrosarcoma
      pathobiology and behaviour. Our analyses revealed that ILK, alpha-parvin, beta
      parvin and Mig-2 are expressed in the majority of chondrosarcomas but in a small
      proportion of enchondromas, implying that these proteins might have a role in the
      development and progression of chondrogenic neoplasms. Moreover, our findings
      highlight the possibilities that ILK might serve as biological marker that could
      accurately predict a high-grade tumour and that Mig-2 may function as a promising
      prognostic indicator of high-risk patients.

PMID- 18722111
TI  - Chemotherapy in metastatic breast cancer: A summary of all randomised trials
      reported 2000-2007.
AB  - AIM: To summarise the findings of all randomised trials comparing chemotherapy
      regimens for metastatic breast cancer that were reported between 2000 and 2007
      inclusive. METHODS: We searched the specialised register of clinical trials
      maintained by the secretariat of the Cochrane Breast Cancer Group (CBCG) from
      2000 to 2007, and abstracts from the American Society of Clinical Oncology (ASCO)
      annual scientific meeting (2000-2007). RESULTS: Eighty reports of 63 trials were
      identified as eligible for this review. Whilst over 30% of the trials reported a
      statistically significant difference in response rate or progression free
      survival, only 8 trials (13%) reported a difference in overall survival. Thirty
      percent reported quality of life data. Very few trials examined the critical
      clinical questions of duration and the relative merits of combination versus
      sequential single agent chemotherapy. CONCLUDING STATEMENT: There is little
      evidence from trials reported from 2000 to 2007 that major survival differences
      exist between many commonly employed chemotherapy regimens.

PMID- 18722109
TI  - Patterns of domestic migrations and access to childhood cancer care centres in
      Italy: a report from the hospital based registry of the Italian Association of
      Pediatric Hematology and Oncology (AIEOP).
AB  - Tertiary care centres, grouped in the Italian Association of Paediatric
      Haematology and Oncology (AIEOP) are unevenly distributed across the country. In
      an attempt to describe their perceived efficacy, we matched the residence and the
      location of the treatment centre in 18,441 patients aged <or=15 years treated in
      the AIEOP network between 1989 and 2005. Overall, centres located in the central
      and southern regions were less appealing than those located in the North,
      although this trend decreased over the study period. Patients with solid tumours
      migrated more frequently than those with leukaemia or lymphoma. Information
      resulting from better knowledge of the non-random migrations for treatment of
      children with cancer will be useful to refine planning of the national paediatric
      haematology-oncology network with social and economic implications.

PMID- 18722110
TI  - Targeting alpha7-nicotinic receptor for the treatment of pleural mesothelioma.
AB  - Human malignant pleural mesothelioma (MPM) is a dreadful disease and there is
      still no standard therapy available for a consistent therapeutic approach. This
      research is aimed at the evaluation of the potential therapeutic effect of a
      specific nicotinic receptor (nAChR) antagonist, namely alpha-Cobratoxin (alpha
      CbT). Its effectiveness was tested in mesothelioma cell lines and in primary
      mesothelioma cells in vitro, as well as in vivo, in orthotopically
      xenotransplanted NOD/SCID mice. Cells showed alpha7-nAChR expression and their
      growth was significantly inhibited by alpha-CbT. Severe induction of apoptosis
      was observed after exposure to alpha-CbT [IC(80-90)]. Apoptosis was characterised
      by: change in mitochondrial potential, caspase-3 cleavage, down-regulation of
      mRNA and protein for survivin, XIAP, IAP1, IAP2 and Bcl-XL, inhibition by caspase
      3 inhibitor. In vivo, the alpha-CbT acute LD(50) was 0.15 mg/kg. The LD(100)
      [0.24 mg/kg] induced fatal respiratory failure and massive kidney necrosis. Phase
      II experiments with 0.12 ng/kg alpha-CbT (1/1000 of LD(10)) were done in 53
      xenotransplanted mice, inhibiting tumour development as confirmed by chest X-ray
      examinations, autopsy and microscopical findings. The growth of human
      proliferating T lymphocytes and of mesothelial cells in primary culture was not
      affected by alpha-CbT. Non-immunogenic derivatives of the alpha-CbT molecule need
      to be developed for possible human use.

PMID- 18722112
TI  - Breast conservation in locally advanced breast cancer in developing countries:
      wise or waste.
AB  - Breast conservation as an additional benefit was beyond the initial expectations
      of the investigators who pioneered neoadjuvant chemotherapy (NACT). In recent
      years an increasing number of patients with locally advanced breast cancer (LABC)
      are being treated with NACT, followed by breast conservation surgery with
      axillary dissection and radiation as a part of the multimodality management.
      Breast conservation has not been the standard of care for women with LABC, owing
      to concerns of increased chances of local recurrence, and possible survival
      disadvantage and psychological trauma from experiencing a recurrence of
      malignancy. LABC is still a common form of presentation of breast cancer in
      developing countries. Strict adherence to treatment protocols and regular follow
      ups for years may not be practical for a large majority of patients hailing from
      the regions most affected by LABC. Defaulters often thus have a heavy price to
      pay. Hence lies the importance of carefully selecting LABC patients for a breast
      conservation approach from others that would have a higher risk of locoregional
      recurrence. Can we extrapolate the lessons learnt in early breast cancer to LABC
      and offer selected patients with LABC breast conservation therapy? Would the
      local control and survival results with conservative therapy be comparable to
      those obtained using mastectomy, or does the increased tumor burden in LABC
      necessitate ablative surgery in all women? This review aims to address these
      important questions.

PMID- 18722113
TI  - Biosorption of pentachlorophenol from aqueous solutions by a fungal biomass.
AB  - This study focuses on the use of non-viable Aspergillus niger biomass, for the
      biosorption of pentachlorophenol (PCP) from aqueous solutions. Various forms of
      the biomass-autoclaved and chemically conditioned, were tested for their
      potential in the removal of PCP from aqueous solutions. It was found that PCP
      removal was pH dependent; PCP removal decreased with the increase in pH for all
      type of biomass, except for cetyltrimethylammonium bromide (CTAB) biomass. For
      CTAB biomass, a near complete removal of PCP was observed at all pHs. Therefore,
      CTAB biomass was used in further studies. PCP removal was rapid, with an
      equilibrium time of 2h. The rate of adsorption kinetics was well described by a
      pseudo-second order model. Isotherm models of the type one and two parameter
      models were found to fit the isotherm data. PCP biosorption was found to be
      exothermic in nature; the amount of PCP sorbed decreased with an increase in
      temperature. Desorption was carried out using deionized water, dilute HCl and
      dilute NaOH, and it was found that most of the PCP was irreversibly bound to the
      biomass. The addition of inorganic salts did not affect the removal of PCP from
      aqueous solutions. Among the surface functional groups present on the biomass,
      carboxyl, amide and hydroxyl groups seem to have played a role in PCP
      biosorption. It was concluded that CTAB treated biomass was an excellent
      adsorbent for the removal of PCP from aqueous solutions.

PMID- 18722114
TI  - Effect of different cellulase dosages on cell viability and ethanol production by
      Kluyveromyces marxianus in SSF processes.
AB  - This study was aimed to study the effect of commercial cellulases (Celluclast 1.5
      LFG) on Kluyveromyces marxianus CECT 10875 growth and ethanol production in SSF
      processes. Preliminary tests carried out in glucose (50 g/L) fermentation medium
      showed that high enzyme amounts (2.5-3.5 FPU/mL) could cause a negative effect on
      K. marxianus growth rate and viable cells number. However, the maximum ethanol
      production was not affected and about 86% of the theoretical (22 g/L) was reached
      in all cases independently of the enzyme dosage. In SSF experiments, cell
      viability was always affected by enzyme loading. Nevertheless, slight differences
      observed on cell viability during glucose fermentation processes with the
      detected concentrations of the additives did not justify the negative effect
      observed in SSF experiments.

PMID- 18722115
TI  - Bradykinin B1 receptor antagonists: an alpha-hydroxy amide with an improved
      metabolism profile.
AB  - A series of carbo- and heterocyclic alpha-hydroxy amide-derived bradykinin B1
      antagonists was prepared and evaluated. A 4,4-difluorocyclohexyl alpha-hydroxy
      amide was incorporated along with a 2-methyl tetrazole in lieu of an oxadiazole
      to afford a suitable compound with good pharmacokinetic properties, CNS
      penetration, and clearance by multiple metabolic pathways.

PMID- 18722116
TI  - Discovery of novel potent and selective dipeptide hepatitis C virus NS3/4A serine
      protease inhibitors.
AB  - Starting from the previously reported HCV NS3/4A protease inhibitor BILN 2061, we
      have used a fast-follower approach to identify a novel series of HCV NS3/4A
      protease inhibitors in which (i) the P3 amino moiety and its capping group have
      been truncated, (ii) a sulfonamide is introduced in the P1 cyclopropyl amino
      acid, (iii) the position 8 of the quinoline is substituted with a methyl or halo
      group, and (iv) the ring size of the macrocycle has been reduced to 14 atoms. SAR
      analysis performed with a limited set of compounds led to the identification of N
      {17-[8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy]-2,14-dioxo
      3,15-diazatricyclo [13.3.0.0 [Bartenschlager, R.; Lohmann, V. J. Gen. Virol.
      2000, 81, 1631; Vincent Soriano, Antonio Madejon, Eugenia Vispo, Pablo Labarga,
      Javier Garcia-Samaniego, Luz Martin-Carbonero, Julie Sheldon, Marcelle
      Bottecchia, Paula Tuma, Pablo Barreiro Expert Opin. Emerg. Drugs, 2008, 13, 1
      19]]octadec-7-ene-4-carbonyl}(1-methylcyclopropyl)(1
      methylcyclopropyl)sulfonamide 19l an extremely potent (K(i)=0.20 nM, EC(50)=3.7
      nM), selective, and orally bioavailable dipeptide NS3/4A protease inhibitor,
      which has features attractive for further preclinical development.

PMID- 18722118
TI  - Substituted aryl pyrimidines as potent and soluble TRPV1 antagonists.
AB  - Clinical candidate AMG 517 (1) is a potent antagonist toward multiple modes of
      activation of TRPV1; however, it suffers from poor solubility. Analogs with
      various substituents at the R region of 3 were prepared to improve the solubility
      while maintaining the potent TRPV1 activity of 1. Compounds were identified that
      maintained potency, had good pharmacokinetic properties, and improved solubility
      relative to 1.

PMID- 18722117
TI  - Synthesis of 3-alkyl naphthalenes as novel estrogen receptor ligands.
AB  - A series of estrogen receptor ligands based on a 3-alkyl naphthalene scaffold was
      synthesized using an intramolecular enolate-alkyne cycloaromatization as the key
      step. Several of these compounds bearing a C6-OH group were shown to be high
      affinity ligands. All compounds had similar ERalpha and ERbeta binding affinity
      ranging from micromolar to low nanomolar.

PMID- 18722119
TI  - 1,5-Dihydro-benzo[e][1,4]oxazepin-2(1H)-ones containing a 7-(5'-cyanopyrrol-2-yl)
      group as nonsteroidal progesterone receptor modulators.
AB  - A series of novel 7-(5'-cyanopyrrol-2-yl) substituted benzo[1,4]oxazepin-2-ones
      were prepared and tested for their progesterone receptor (PR) agonist or
      antagonist activity in the alkaline phosphatase assay using the human T47D breast
      carcinoma cell line. Both PR agonists and antagonists were achieved with an
      appropriate choice of 5-substitution. Several analogs were potent PR agonists
      (e.g., 12 and 13) or PR antagonists (e.g., 18) with good selectivity over other
      steroid receptors.

PMID- 18722120
TI  - Synthesis and evaluation of cis-3,4-disubstituted piperidines as potent CC
      chemokine receptor 2 (CCR2) antagonists.
AB  - A series of cis-3,4-disubstituted piperidines was synthesized and evaluated as CC
      chemokine receptor 2 (CCR2) antagonists. Compound 24 emerged with an attractive
      profile, possessing excellent binding (CCR2 IC(50)=3.4 nM) and functional
      antagonism (calcium flux IC(50)=2.0 nM and chemotaxis IC(50)=5.4 nM). Studies to
      explore the binding of these piperidine analogs utilized a key CCR2 receptor
      mutant (E291A) with compound 14 and revealed a significant reliance on Glu291 for
      binding.

PMID- 18722121
TI  - Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated
      raptor phosphorylation.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) is a Ser/Thr kinase that
      controls cell growth in response to mitogens, as well as amino acid and energy
      sufficiency. The scaffolding protein Raptor binds to mTOR and recruits substrates
      to the rapamycin-sensitive mTOR complex 1 (mTORC1). Although Raptor has been
      shown to be essential for mTORC1 activity, the mechanisms regulating Raptor
      function remain unknown. RESULTS: Here, we demonstrate that Raptor becomes highly
      phosphorylated on RXRXXpS/T consensus motifs after activation of the Ras/mitogen
      activated protein kinase (MAPK) pathway. Using pharmacological inhibitors and RNA
      interference, we show that the p90 ribosomal S6 kinases (RSKs) 1 and 2 are
      required for Raptor phosphorylation in vivo and directly phosphorylate Raptor in
      vitro. Quantitative mass spectrometry and site-directed mutagenesis revealed that
      RSK specifically phosphorylates Raptor within an evolutionarily conserved region
      with no previously known function. Interestingly, expression of oncogenic forms
      of Ras and MEK that elevate mTORC1 activity induced strong and constitutive
      phosphorylation of Raptor on these residues. Importantly, we demonstrate that
      expression of Raptor mutants lacking RSK-dependent phosphorylation sites markedly
      reduced mTOR phosphotransferase activity, indicating that RSK-mediated
      phosphorylation of Raptor is important for mTORC1 activation by the Ras/MAPK
      pathway. CONCLUSIONS: We propose a unique mode of mTOR regulation in which RSK
      mediated phosphorylation of Raptor regulates mTORC1 activity and thus suggest a
      means by which the Ras/MAPK pathway might promote rapamycin-sensitive signaling
      independently of the PI3K/Akt pathway.

PMID- 18722122
TI  - Regulation of mitotic spindle asymmetry by SUMO and the spindle-assembly
      checkpoint in yeast.
AB  - During mitosis, the kinetochore microtubules capture and segregate chromosomes,
      and the astral microtubules position the spindle within the cell. Although the
      spindle is symmetric, proper positioning of the spindle in asymmetrically
      dividing cells generally correlates with the formation of morphologically and
      structurally distinct asters [1]. In budding yeast, the spindle-orientation
      proteins Kar9 and dynein decorate only one aster of the metaphase spindle and
      direct it toward the bud [2, 3]. The mechanisms controlling the distribution of
      Kar9 and dynein remain unclear. Here, we show that SUMO regulates astral
      microtubule function in at least two ways. First, Kar9 was sumoylated in vivo.
      Sumoylation and Cdk1-dependent phosphorylation of Kar9 independently promoted
      Kar9 asymmetry on the spindle. Second, proper regulation of kinetochore function
      by SUMO was also required for Kar9 asymmetry. Indeed, activation of the spindle
      assembly checkpoint (SAC) due to SUMO and kinetochore defects promoted symmetric
      redistribution of Kar9 in a Mad2-dependent manner. The control of Kar9
      distribution by the SAC was independent of Kar9 sumoylation and phosphorylation.
      Together, our data reveal that three independent mechanisms contribute to Kar9
      asymmetry: Cdk1-dependent phosphorylation, sumoylation, and SAC signaling. Hence,
      the two seemingly independent spindle domains, kinetochores and astral
      microtubules, function in a tightly coordinated fashion.

PMID- 18722123
TI  - Transportin-SR2 imports HIV into the nucleus.
AB  - BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) and other
      lentiviruses have the capacity to infect nondividing cells like macrophages. This
      requires import of the preintegration complex (PIC) through the nuclear pore.
      Although many cellular and viral determinants have been proposed, the mechanism
      leading to nuclear import is not yet understood. RESULTS: Using yeast two-hybrid
      and pull-down, we identified and validated transportin-SR2 (TRN-SR2) as a bona
      fide binding partner of HIV-1 integrase. We confirmed the biological relevance of
      this interaction by RNAi. Depletion of TRN-SR2 interfered with the replication of
      HIV-1 and HIV-2 but not MoMLV in HeLaP4 cells. Knockdown of TRN-SR2 in primary
      macrophages likewise interfered with HIV-1 replication. Using Q-PCR, we pinpoint
      this block in replication to the early steps of the viral lifecycle. A reduction
      in 2-LTR formation suggests a block in PIC nuclear import upon siRNA-mediated
      knockdown. Different lines of evidence clearly proved that the late steps of
      viral replication are not affected. In an in vivo nuclear-import assay using
      labeled HIV-1 particles, the defect in nuclear import after depletion of TRN-SR2
      was directly visualized. In comparison with control cell lines, the great
      majority of siRNA-treated cells did not contain any PIC in the nucleus.
      CONCLUSION: Our data clearly demonstrate that TRN-SR2 is the nuclear-import
      factor of HIV.

PMID- 18722125
TI  - Re: Gait and balance of transfemoral amputees using passive mechanical and
      microprocessor controlled prosthetic knees by Kaufman et al. [Gait and Posture 20
      (2007) 489-493].

PMID- 18722126
TI  - Biomechanical analysis of retrograde intramedullary nail fixation in distal
      femoral fractures.
AB  - This study employed both mechanical testing and finite element analysis to
      compare the stiffness variations among different intramedullary nail constructs
      used in the treatment of distal femoral fractures. Compressive and torsional
      experiments were conducted on a transversely, as well as an obliquely fractured
      sawbone femur restored with the retrograde intramedullary nail. Corresponding
      finite element models were established to evaluate the stress distributions
      around screw holes. The results showed that a perifracture screw could increase
      stiffness by 40% for the obliquely fractured femur, but that it played an
      insignificant role in stiffness improvement for the transverse fracture groups.
      Moreover, compared to proximal-screw fixation, distal-screw fixation could
      improve construct stiffness by 20%. The absence of one of the two distal screws
      would increase the screw-hole stress by 70%. Therefore, the distal screw around
      the metaphyseal region has a more important stabilizing effect in the femur-nail
      construct than does the proximal screw. A twisting stress pattern occurs on the
      unused screw holes of the metaphyseal region and induces a higher risk for
      fatigue fracture. The locking screw at the fracture site would be most effective
      only if it passed through the fracture gap to integrate the separated femoral
      pieces.

PMID- 18722124
TI  - Membrane localization of scaffold proteins promotes graded signaling in the yeast
      MAP kinase cascade.
AB  - BACKGROUND: Signaling through mitogen-activated protein kinase (MAPK) cascade
      pathways can show various input-output behaviors, including either switch-like or
      graded responses to increasing levels of stimulus. Prior studies suggest that
      switch-like behavior is promoted by positive feedback loops and nonprocessive
      phosphorylation reactions, but it is unclear whether graded signaling is a
      default behavior or whether it must be enforced by separate mechanisms. It has
      been hypothesized that scaffold proteins promote graded behavior. RESULTS: Here,
      we experimentally probe the determinants of graded signaling in the yeast mating
      MAPK pathway. We find that graded behavior is robust in that it resists
      perturbation by loss of several negative-feedback regulators. However, the
      pathway becomes switch-like when activated by a crosstalk stimulus that bypasses
      multiple upstream components. To dissect the contributing factors, we developed a
      method for gradually varying the signal input at different pathway steps in vivo.
      Input at the beginning of the kinase cascade produced a sharp, threshold-like
      response. Surprisingly, the scaffold protein Ste5 increased this threshold
      behavior when limited to the cytosol. However, signaling remained graded whenever
      Ste5 was allowed to function at the plasma membrane. CONCLUSIONS: The results
      suggest that the MAPK cascade module is inherently ultrasensitive but is
      converted to a graded system by the pathway-specific activation mechanism.
      Scaffold-mediated assembly of signaling complexes at the plasma membrane allows
      faithful propagation of weak signals, which consequently reduces pathway
      ultrasensitivity. These properties help shape the input-output properties of the
      system to fit the physiological context.

PMID- 18722127
TI  - Design, synthesis and biological evaluation of dihydronaphthalene and
      benzosuberene analogs of the combretastatins as inhibitors of tubulin
      polymerization in cancer chemotherapy.
AB  - A novel series of dihydronaphthalene and benzosuberene analogs bearing structural
      similarity to the combretastatins in terms of 1,2-diarylethene, trimethoxyphenyl,
      and biaryl functionality has been synthesized. The compounds have been evaluated
      in regard to their ability to inhibit tubulin assembly and for their cytotoxicity
      against selected human cancer cell lines. From this series of compounds,
      benzosuberene analogs 2 and 4 inhibited tubulin assembly at concentrations
      comparable to that of combretastatin A-4 (CA4) and combretastatin A-1 (CA1).
      Furthermore, analog 4 demonstrated remarkable cytotoxicity against the three
      human cancer cell lines evaluated (for example GI(50)=0.0000032 microM against DU
      145 prostate carcinoma).

PMID- 18722128
TI  - Synthesis of new 1-phenyl-3-{4-[(2E)-3-phenylprop-2-enoyl]phenyl}-thiourea and
      urea derivatives with anti-nociceptive activity.
AB  - Chalcones or 1,3-diaryl-2-propen-1-ones are known to be useful for treating pain,
      inflammation, and certain diseases although their uses have not been
      scientifically verified. Due to the limitations of opioid and NSAID therapy,
      there is a continuing search for new analgesics. A series of novel new 1-phenyl-3
      {4-[(2E)-3-phenylprop-2-enoyl]phenyl}-thiourea and urea derivatives were
      synthesized and evaluated against writhing test in mice, following the aromatic
      substitution pattern proposed by Topliss. The results of the preliminary
      bioassays indicate that compound 3 presents promising anti-nociceptive activity
      in acetic acid-, formalin-, and glutamate-induced pain in mice, compared with
      some well-known non-steroidal anti-inflammatory and analgesic drugs.

PMID- 18722129
TI  - Novel angular furoquinolinones bearing flexible chain as antitumor agent: design,
      synthesis, cytotoxic evaluation, and DNA-binding studies.
AB  - A series of novel N-substituted angular furoquinolinone derivatives were
      synthesized and evaluated for their antitumor activities against QGY, K562, HeLa,
      P388, and A549 cell lines in vitro. The derivatives bearing basic amino side
      chain showed an improved antitumor activity. Compound 5h N-(2-dimethylamino
      ethyl)-2-(4,8,9-trimethyl-2-oxo-2H-furo[2,3-h]quinolin-1-yl)-acetamide exhibited
      the highest activities against P388 and A549 cell lines, which are evidenced by
      the IC(50) values that are four to five fold lower than that for unsubstituted
      parent compound. DNA-binding experiments suggested that these derivatives bind to
      DNA through intercalation.

PMID- 18722130
TI  - Synthesis and biological properties of 2-methylene-19-nor-25-dehydro-1alpha
      hydroxyvitamin D(3)-26,23-lactones--weak agonists.
AB  - In a continuing effort to explore the 2-methylene-1alpha-hydroxy-19-norvitamin
      D(3) class of pharmacologically important vitamin D compounds, two novel 2
      methylene-19-nor-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactones, GC-3 and
      HLV, were synthesized and biologically tested. Based on reports of similarly
      structured molecules, it was hypothesized that these compounds might act as
      antagonists, at least in vitro. The pathway designed to synthesize these
      compounds was based on two key steps: first, the Lythgoe-type Wittig-Horner
      coupling of Windaus-Grundmann-type ketone 18, with phosphine oxide 15, followed,
      later in the synthesis, by the Zn-mediated Reformatsky-type allylation of
      aldehyde 20 with methylbromomethylacrylate 8. Our biological data show that
      neither compound has antagonistic activity but acts as weak agonists in vitro and
      in vivo.

PMID- 18722132
TI  - Clinical implication and prognostic significance of standardised uptake value of
      primary non-small cell lung cancer on positron emission tomography: analysis of
      176 cases.
AB  - OBJECTIVE: We sought to assess the clinical implication and prognostic
      significance of maximum standardised uptake value (SUV(max)) of primary non-small
      cell lung cancer (NSCLC) staged by integrated PET-CT. METHODS: A retrospective
      review was carried out on 176 consecutive patients with histologically proven
      NSCLC who underwent staging with integrated PET-CT prior to curative intent
      surgical resection. SUV(max) of primary NSCLC were measured and correlated with
      tumour characteristics, lymph node involvement, surgical stage, type of surgical
      resection and survival following resection. RESULTS: SUV(max) was significantly
      higher in centrally located tumours, tumours > or =4.0 cm, squamous cell subtype,
      poorly differentiated tumours, advanced T stage, advanced nodal stage, pleural
      invasion, and patients requiring complex surgical resection. SUV(max) value of 15
      was the best discriminative cut-off value for survival generated by log-rank
      test. When patients were stratified based on this value, those with SUV(max) >15
      were more likely to have centrally located tumours, squamous cell subtype,
      advanced T stage, advanced nodal stage, advanced American Joint Committee on
      Cancer (AJCC) stage, larger tumour size and required more advanced surgical
      resections than a simple lobectomy. Overall survival was significantly longer for
      patients with SUV(max) < or =15 than those with SUV(max) >15. Furthermore, nodal
      stage specific survival following resection (i.e. non-N2 and N2) were
      significantly better in patients with SUV(max) < or =15 than SUV(max) >15.
      CONCLUSION: SUV(max) correlates with tumour characteristics, surgical stage and
      prognosis following resection. SUV(max) may be a useful preoperative tool, in
      addition to other known prognostic markers, in allocating patients with
      potentially poor prognosis preoperatively to neoadjuvant chemotherapy prior to
      resection in order to improve their overall survival. Prospective and randomised
      trials are warranted.

PMID- 18722133
TI  - Better the devil you know?

PMID- 18722134
TI  - Subclinical idiopathic pulmonary fibrosis is also a risk factor of postoperative
      acute respiratory distress syndrome following thoracic surgery.
AB  - OBJECTIVE: Postoperative acute interstitial pneumonia is a subset of post
      surgical acute respiratory distress syndrome (ARDS) and is responsible for one
      third of in-hospital deaths following lung resection in patients with primary
      lung cancer. We evaluated the usefulness of computed tomography (CT) for
      detection of interstitial pneumonia (IP) as a risk factor of postoperative ARDS.
      METHODS: Preoperative chest CT of patients who underwent thoracotomy for primary
      lung cancer was reviewed retrospectively and IP findings in the chest CT were
      detected. RESULTS: A total of 1148 patients with primary lung cancer underwent
      thoracotomy. Fifteen patients (1.3%) developed postoperative ARDS. Eleven of
      these 15 patients died of ARDS. Three of 41 patients who received induction
      therapy developed postoperative ARDS. Induction therapy was a risk factor of
      postoperative ARDS (p<0.01). Eleven out of the 15 patients who developed
      postoperative ARDS had IP findings (10: localized, 1: diffuse) in their chest CT.
      Two of three patients who had postoperative ARDS after induction therapy also had
      IP findings. Chest CTs of 834 patients were retrospectively analyzed; 91 patients
      (10.9%) had IP-findings (diffuse 1.8%, localized 9.1%). Postoperative ARDS
      occurred in 8.8% of IP-positive patients, and in 0.4% of IP-negative patients
      (p<0.001). CONCLUSION: Detection of IP by chest CT is useful for the selection of
      high-risk patients who may have postoperative ARDS following thoracotomy.

PMID- 18722135
TI  - Chemotaxis, chemokine receptors and human disease.
AB  - Cell migration is involved in diverse physiological processes including
      embryogenesis, immunity, and diseases such as cancer and chronic inflammatory
      disease. The movement of many cell types is directed by extracellular gradients
      of diffusible chemicals. This phenomenon, referred to as "chemotaxis", was first
      described in 1888 by Leber who observed the movement of leukocytes toward sites
      of inflammation. We now know that a large family of small proteins, chemokines,
      serves as the extracellular signals and a family of G-protein-coupled receptors
      (GPCRs), chemokine receptors, detects gradients of chemokines and guides cell
      movement in vivo. Currently, we still know little about the molecular machineries
      that control chemokine gradient sensing and migration of immune cells.
      Fortunately, the molecular mechanisms that control these fundamental aspects of
      chemotaxis appear to be evolutionarily conserved, and studies in lower eukaryotic
      model systems have allowed us to form concepts, uncover molecular components,
      develop new techniques, and test models of chemotaxis. These studies have helped
      our current understanding of this complicated cell behavior. In this review, we
      wish to mention landmark discoveries in the chemotaxis research field that shaped
      our current understanding of this fundamental cell behavior and lay out key
      questions that remain to be addressed in the future.

PMID- 18722136
TI  - Increased intestinal inflammatory response and gut barrier dysfunction in Nrf2
      deficient mice after traumatic brain injury.
AB  - AIM: To explore the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in
      traumatic brain injury (TBI)-induced intestinal inflammatory response and gut
      barrier dysfunction in the mice. METHODS: Wild-type Nrf2 (+/+) and Nrf2 (-/-)
      deficient mice were subjected to a moderately severe weight-drop impact
      acceleration head injury. We measured nuclear factor kappa B (NF-kappaB) by
      electrophoretic mobility shift assay (EMSA); tumor necrosis factor-alpha (TNF
      alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) by enzyme-linked
      immunosorbent assay (ELISA); intercellular adhesion molecule-1 (ICAM-1) by
      immunohistochemistry; intestinal permeability by lactulose/mannitol (L/M) test;
      plasma endotoxin by chromogenic limulus amebocyte lysate test. RESULTS:
      Intestinal levels of NF-kappaB, pro-inflammatory cytokines and ICAM-1 in Nrf2 (-/
      )-deficient mice were significantly higher compared with Nrf2 (+/+) mice at 24h
      after TBI. Furthermore, higher intestinal permeability and plasma level of
      endotoxin were observed in the Nrf2 (-/-) mice compared with Nrf2 (+/+) mice.
      CONCLUSION: Nrf2 plays an important protective role in limiting intestinal
      inflammatory response and gut barrier dysfunction after TBI.

PMID- 18722137
TI  - Cerebrospinal fluid levels of cytokines in non-herpetic acute limbic
      encephalitis: comparison with herpes simplex encephalitis.
AB  - BACKGROUND: Recently, non-herpetic acute limbic encephalitis (NHALE) was
      identified as a new subgroup of limbic encephalitis. The immunological
      pathophysiology of NHALE is still unclear. METHODS: We measured the
      concentrations of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF
      alpha), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and soluble TNF receptor 1
      (sTNFR1) in the cerebrospinal fluid (CSF) of 15 patients with NHALE and 13 with
      herpes simplex encephalitis (HSE) by cytometric bead array or ELISA. RESULTS: The
      CSF concentrations of IL-6 in patients with NHALE and IFN-gamma, IL-6, IL-10, and
      sTNFR1 in HSE patients were significantly higher than those of controls (p<0.001,
      p=0.004, p<0.001, p=0.018, and p<0.001, respectively). There were significant
      correlations among CSF IL-6, IL-10, and sTNFR1 levels in HSE patients. The CSF
      concentrations of IFN-gamma and sTNFR1 levels of patients with HSE were
      significantly higher than those with NHALE (p=0.001 and p=0.002, respectively).
      CONCLUSIONS: CSF cytokine levels in NHALE were relatively low compared with those
      in HSE. These results may be related to the favorable prognosis of NHALE.

PMID- 18722138
TI  - Atmospheric pressure thermal dissociation of phospho- and sulfopeptides.
AB  - Several phospho- and sulfopeptides were subjected to atmospheric pressure thermal
      dissociation (APTD), which was effected by passing peptide ions generated by
      electrosonic spray ionization (ESSI) through a heated coiled metal tube. Sequence
      informative fragment ions including a-, b-, c-, and y-types of ions were observed
      with increased relative intensities under APTD compared with collision-induced
      dissociation (CID), performed inside the ion trap. A certain degree of
      preservation of phosphate and sulfate ester moieties was observed for some
      fragments ions under APTD. The neutral fragments generated outside the mass
      spectrometer were further analyzed via on-line corona discharge to provide rich
      and complementary sequence information to that provided by the fragment ions
      directly obtained from APTD, although complete losses of the modification groups
      were noted. Improved primary sequence information for phospho- and sulfopeptides
      was typically obtained by analyzing both ionic and neutral fragments from APTD
      compared with fragment ions from CID alone. Localization of the modification
      sites of phospho- and sulfopeptides was achieved by combining the structural
      information acquired from APTD and CID.

PMID- 18722140
TI  - Optimising the timing of carotid surgery using a carotid risk scoring system.
AB  - OBJECTIVES: Transient ischaemic attacks (TIA's) have 4-20% risk of evolving into
      a major stroke within 90 days, with half of them occurring in the first 2 days.
      The Department of Health, UK, guidelines (2007) suggests all higher-risk patients
      with TIA and minor stroke need to be assessed by a specialist and treated within
      24 hours. However, the reality in the health system is that the delay between the
      last cerebrovascular event (CVE) and surgery is often in excess of 90 days.
      Recently validated ABCD(2) scoring stratifies the risk of stroke after CVE and
      can help in prioritizing patients for investigations and urgent carotid
      endarterectomy (CEA). The aim of this pilot study was to stratify patients who
      underwent CEA, post cerebrovascular event, using the ABCD(2) scoring method. This
      would help us assess our current CEA practice and, in future, prioritise surgery
      according to estimated stroke risk. DESIGN & METHODS: Retrospective analysis of
      ABCD(2) scoring of patients who underwent CEA. RESULTS: The average delay between
      first presentation and carotid endarterectomy was 172.8 days (range 3 to 837
      days). This average delay for the low, moderate and high risk groups was 200.8,
      154.1 and 156.5 days, respectively. CONCLUSION: The ABCD(2) scoring is an easily
      applicable method to stratify patients post CVE at risk of further stroke. Our
      results suggest that to maximize the benefit of CEA within a limited resource
      health system, patients with a high ABCD(2) score should be given the highest
      priority for investigations followed by CEA.

PMID- 18722139
TI  - Early B cell factor: Regulator of B lineage specification and commitment.
AB  - B lymphocytes are generated from hematopoietic stem cells in a series of steps
      controlled by transcription factors. One of the most important regulators of this
      process is early B cell factor (EBF). Multiple lines of evidence indicate that
      expression of EBF is a principle determinant of the B cell fate. In the absence
      of EBF, progenitor cells fail to express classical markers of B cells, including
      immunoglobulins. EBF drives B cell differentiation by activating the Pax5 gene
      and other genes required for the pre-B and B cell receptors. New evidence
      suggests that expression of EBF in common lymphoid progenitors directs B cell
      fate decisions. Specification and commitment of cells to the B cell lineage are
      further established by Pax5, which increases expression of EBF. Recently, it was
      demonstrated that both EBF and Pax5 contribute to the commitment of cells to the
      B lineage. Together, these studies confirm that EBF is a keystone in the
      regulatory network that coordinates B cell lineage specification and commitment.

PMID- 18722141
TI  - Is robotic surgery appropriate for vascular procedures? Report of 100 aortoiliac
      cases.
AB  - AIM: The aim of our study was to evaluate our clinical experience of the da
      Vincitrade mark system for robot-assisted aortoiliac reconstructions to treat
      occlusive disease and aneurysm. MATERIAL AND METHODS: Between November 2005 and
      January 2008 100 consecutive patients were scheduled to undergo robot-assisted
      laparoscopic aortoiliac procedures. Patients with serious medical problems and
      those who had previously undergone major abdominal surgery were excluded from the
      clinical study. Ninety patients were prospectively evaluated for arterial
      occlusive disease (AOD), seven patients for abdominal aortic aneurysms (AAA), two
      for common iliac artery aneurysms (CIAA) and one for a combination of CIAA and
      AOD. RESULTS: Ninety-seven of 100 procedures (97%) were successfully completed
      robotically, while conversions were necessary in three patients (3%). The median
      operating time was 235 minutes (range 150 to 360 minutes), with a median clamp
      time of 42 minutes (range 25 to 120 minutes). The median anastomosis time was 29
      minutes (range 12 to 60 minutes) and median blood loss was 430mL (range 50 to
      1500mL). The median intensive care unit stay was 1.7 days and the median hospital
      stay was 5.1 days. A regular oral diet was resumed after a mean of 2.4 days.
      Thirty-day survival was 100% and non-lethal postoperative complications were
      observed in three patients (3%). CONCLUSIONS: Robotic aortoiliac surgery appears
      to be safe, with a high technical success rate, with operative times and success
      rates comparable to conventional open surgery. The creation of the aortoiliac
      anastomosis appears to be quicker, and more accurate than regular laparoscopic
      techniques.

PMID- 18722142
TI  - Endovascular repair of an aortic arch aneurysm using a branched-stent graft.
AB  - INTRODUCTION: Aortic arch aneurysm repair continues to pose a formidable
      technical challenge in a patient population with significant co-morbidity.
      REPORT: We present a successful endovascular repair of an 8.4 cm aortic arch
      aneurysm, in a 74 year old man, who's previous median sternotomy showed signs of
      delayed healing, precluding open repair. DISCUSSION: Applied endovascular
      techniques obviated the need for aortic clamping, cardiac bypass, or hypothermic
      circulatory arrest, via an approach that was potentially infected.

PMID- 18722143
TI  - Litigation claims in vascular surgery in the United Kingdom's NHS.
AB  - OBJECTIVES: To establish the incidence, costs and causes of medical negligence
      claims in relation to vascular surgery in the UK's NHS. METHODS: All claims
      related to vascular surgery reported to the NHS Litigation Authority from April
      1995 to April 2007 were included in the study. Data was subsequently reviewed,
      coded and analysed. RESULTS: 395 claims were identified (mean: 49/year over last
      5 years) of which 303 had been settled. Damage compensation was given in 160
      cases, with overall litigation costs of approximately 17 million pounds (21
      million euros). The main complaint reasons in successful claims were intra
      operative problems (50%), failure/delay of treatment (14%) and failure/delay of
      diagnosis (11%). Varicose vein (VV) surgery was involved in 48% of successful
      claims, with intra-operative nerve and vessel damage being the major causes.
      Peripheral vascular disease (PVD) and abdominal aortic aneurysm (AAA) disease
      were the next two types of disease/procedures involved in successful claims with
      21% and 6% respectively. CONCLUSIONS: The number of claims related to vascular
      surgery has remained stable over the past 5 years. Improved consenting and higher
      surgical skill levels especially in relation to VV surgery and increased
      diagnostic vigilance in PVD, AAA disease and infections are potential areas for
      future improvement.

PMID- 18722144
TI  - Ten years experience of treating aorto-femoral bypass graft infection with venous
      allografts.
AB  - OBJECTIVE: The aim of the present study was to analyze our results of treating
      synthetic vascular graft infection in the aorto-femoral segment with venous
      allografts. PATIENTS AND METHODS: During 1997-2006 we treated 11 male patients
      with venous allografts for aorto-femoral segment prosthetic graft infection.
      Patients were followed postoperatively with patency assessment based on Doppler
      ultrasonography. RESULTS: The mean interval between the implantation of the
      synthetic vascular graft and the appearance of infection was 43+/-29 months
      (range 5 months-10 years). Overall primary patency of the venous allograft was
      100%, 88% and 66% at 1, 6 and 36 months, respectively. Secondary patency rates of
      the venous allograft were 94% and 73% after 5 and 8 years, respectively. Overall
      survival rate was 100%, 64%, 46% and 27% after one month, 3, 5 and 8 years,
      respectively. Limb salvage rate was 100%, 94% and 73% after 1 month, 5 and 8
      years, respectively. CONCLUSIONS: The use of in situ venous allograft for the
      treatment of synthetic graft infection in the aorto-femoral segment has led to
      favourable short- and long-term results.

PMID- 18722146
TI  - Brain abnormalities in Williams syndrome: a review of structural and functional
      magnetic resonance imaging findings.
AB  - Williams syndrome (WS) is rare genetic form of mental retardation caused by a
      microdeletion on chromosome 7q11.23 that causes cognitive impairment and a
      variety of physical abnormalities. MRI studies of WS have demonstrated a series
      of brain abnormalities, including decreased brain size, with a relatively greater
      decrease in the volume of the cerebral white matter volume as compared to the
      cerebral gray matter. Moreover there is evidence that the posterior cerebrum is
      more affected in that persons with WS have a greater ratio of frontal to
      posterior regional volume. These findings are further supported by automated
      analyses that have shown reduced gray matter density in the superior parietal
      lobe areas. Functional MRI studies have demonstrated hypofunction immediately
      adjacent to, and anterior to, the intraparietal sulcus, a region in which
      structural brain differences had been identified. These anatomical and functional
      differences are consistent with the neuropsychological profile of WS - in
      particular, with evidence of dorsal stream visual processing deficits. To date,
      however, studies have always been performed in comparison to intellectually
      average controls. It is not clear, therefore, if findings are specific to the WS
      population or whether they represent a morphological disturbance characteristic
      of mental retardation, irrespective of genetic etiology. In this article, we
      reviewed recent advances underlying the structural and functional neural
      substrate of WS in Medical Literature Analysis and Retrieval System Online
      (MEDLINE; 1997-2007).

PMID- 18722145
TI  - Hip dysplasia in Estrela mountain dogs: prevalence and genetic trends 1991-2005.
AB  - Three hundred and thirteen Estrela mountain dogs were examined for hip dysplasia
      (HD) using the standard ventrodorsal hip extended view, and graded into five
      categories (A, B, C, D and E) using the Federation Cynologique Internationale's
      (FCI) scoring system. The Ortolani method was performed to evaluate hip joint
      laxity. Pedigree information was obtained from the Portuguese Kennel Club and the
      genetic trend was evaluated by calculating the mean breeding values (BVs) for the
      last 15 years, using the threshold model. HD was found in 66% of the dogs. There
      was low-moderate correlation between the results of the Ortolani test and FCI hip
      scores (r(s)=0.386; P<0.001). Grades of hip dysplasia were equal in both males
      and females (P=0.14) and in the animals' right and left sides (P=0.51). The mean
      BVs for HD were stable in dogs born between 1991 and 2003, and showed an
      improvement in 2004 and 2005. The data confirm the high prevalence and severity
      of HD in predisposed breeds that do not have breeding programmes in place. It
      also confirms an initial favourable change in BVs that is a likely consequence of
      the voluntary radiographic hip-screening programme.

PMID- 18722147
TI  - Perinatal dyskinesia as a presenting feature in Prader Willi syndrome.
AB  - Prader Willi Syndrome (PWS) is a complex genetic disorder. Infants present with
      hypotonia and feeding difficulties, usually without respiratory symptoms, but
      with distinctive facial features. Early neonatal diagnosis can however be
      difficult in children with only subtle distinctive appearances or with atypical
      clinical signs, leading to a significant delay in the diagnosis. To highlight the
      diagnostic difficulties we reviewed our experience of infants with PWS referred
      to our tertiary centre. We describe 14 patients, 10 of whom presented in the
      neonatal period. All had axial hypotonia, and poor feeding. Twelve had a paucity
      of movement, 11 had distinctive features and 10 had a reduced level of alertness
      in the neonatal period. In addition to these typical features, four patients had
      prominent limb dyskinesia, which has only been reported once before in infants
      with PWS. We draw attention to this relatively common but poorly acknowledged
      sign that can be seen at presentation of PWS.

PMID- 18722148
TI  - Evaluation of a commercial VMC++ Monte Carlo based treatment planning system for
      electron beams using EGSnrc/BEAMnrc simulations and measurements.
AB  - In the present work, Monte Carlo (MC) models of electron beams (energies 4, 12
      and 18MeV) from an Elekta SL25 medical linear accelerator were simulated using
      EGSnrc/BEAMnrc user code. The calculated dose distributions were benchmarked by
      comparison with measurements made in a water phantom for a wide range of open
      field sizes and insert combinations, at a single source-to-surface distance (SSD)
      of 100cm. These BEAMnrc models were used to evaluate the accuracy of a commercial
      MC dose calculation engine for electron beam treatment planning (Oncentra
      MasterPlan Treament Planning System (OMTPS) version 1.4, Nucletron) for two
      energies, 4 and 12MeV. Output factors were furthermore measured in the water
      phantom and compared to BEAMnrc and OMTPS. The overall agreement between
      predicted and measured output factors was comparable for both BEAMnrc and OMTPS,
      except for a few asymmetric and/or small insert cutouts, where larger deviations
      between measurements and the values predicted from BEAMnrc as well as OMTPS
      computations were recorded. However, in the heterogeneous phantom, differences
      between BEAMnrc and measurements ranged from 0.5 to 2.0% between two ribs and 0.6
      1.0% below the ribs, whereas the range difference between OMTPS and measurements
      was the same (0.5-4.0%) in both areas. With respect to output factors, the
      overall agreement between BEAMnrc and measurements was usually within 1.0%
      whereas differences up to nearly 3.0% were observed for OMTPS. This paper focuses
      on a comparison for clinical cases, including the effects of electron beam
      attenuations in a heterogeneous phantom. It, therefore, complements previously
      reported data (only based on measurements) in one other paper on commissioning of
      the VMC++ dose calculation engine. These results demonstrate that the VMC++
      algorithm is more robust in predicting dose distribution than Pencil beam based
      algorithms for the electron beams investigated.

PMID- 18722149
TI  - Is there an evidence-based efficacy for the use of foot orthotics in knee and hip
      osteoarthritis? Elaboration of French clinical practice guidelines.
AB  - OBJECTIVE: To develop clinical practice guidelines for the use of foot orthotics
      (FO) in the treatment of knee and hip osteoarthritis. METHOD: The SOFMER (French
      Physical Medicine and Rehabilitation Society) methodology, associating a
      systematic review of the literature, input from every day clinical practice and
      external review by a multidisciplinary expert committee, was used. The selected
      analysis criteria were pain, disability, medications used and X-ray evolution of
      osteoarthritis. The recommendations are classified according to the level of
      proof in Grade A, B or C according to the French National Agency for Health
      Accreditation and Evaluation (NAHAE). RESULTS: In medial knee osteoarthritis,
      foot pronation orthotics--when there are no contraindications--can be proposed
      for their symptomatic impact, especially in the decrease of NSAIDs consumption
      (Grade B). To this day, there is no evidence of a structural or functional impact
      on osteoarthritis (Grade B). Outside of this specific clinical framework, there
      is no validated indication for prescribing foot orthotics in the treatment of
      knee or hip OA (Grade C). CONCLUSION: It is necessary to have further randomized
      controlled trials to better define the indication of Foot orthotics (severity of
      knee OA, genu varum), test the efficacy of other orthoses such as cushioning FO.
      The long-term side effects, mainly on the external femorotibial compartment could
      also be assessed. A medical and economical assessment of FO prescriptions is also
      quite necessary.

PMID- 18722150
TI  - Influence of antegrade pulmonary blood flow on the hemodynamic performance of
      bidirectional cavopulmonary anastomosis: a numerical study.
AB  - The role and effect of preserved antegrade pulmonary blood flow (APBF) at the
      time of bidirectional cavopulmonary anastomosis (BCPA) in the management of
      single-ventricle physiology is controversial. We investigated the influence of
      APBF on the fluid dynamics of BCPA connection using computational fluid dynamics
      (CFD). Patient-specific, three-dimensional geometry of a BCPA connection with
      native pulmonary artery (PA) trunk was reconstructed and transient CFD
      simulations were done at four predetermined mean flow rates of PA trunk
      (0.5L/min, 1L/min, 1.5L/min and 2L/min). During a cardiac cycle, the flow ratio
      of left pulmonary artery (LPA)/right pulmonary artery (RPA) increased from 1.91
      to 2.50, and average control volume power loss increased from 0.76 mW to 18.05 mW
      when the mean flow rate of PA trunk changed from 0.5L/min to 2L/min. The
      pulsatility of pressures in LPA, RPA and superior vena cava became more prominent
      as the amount of APBF increased. Local fluid structures in the connection area at
      four levels of APBF differed from each other.

PMID- 18722151
TI  - Inequality in obesigenic environments: fast food density in New York City.
AB  - The high prevalence of obesity in African American populations may be due to the
      food environment in residential communities, and the density of fast food
      restaurants is an important aspect of the restaurant landscape in US cities. This
      study investigated racial and socioeconomic correlates of fast food density in
      New York City. We found that predominantly Black areas had higher densities of
      fast food than predominantly White areas; high-income Black areas had similar
      exposure as low-income Black areas; and national chains were most dense in
      commercial areas. The results highlight the importance of policy level
      interventions to address disparities in food environments as a key goal in
      obesity prevention efforts.

PMID- 18722152
TI  - New spaces of inpatient care for people with mental illness: a complex 'rebirth'
      of the clinic?
AB  - This paper examines the implications for design of inpatient settings of
      community-based models of care and treatment of mental illness. The study draws
      on ideas from relational geographies and expands interpretations based on
      Foucault's writing. We analyse material from a case study which explored the
      views of patients, consultants, and other staff from a new Psychiatric Inpatient
      Unit in a deprived area of East London, UK. We discuss in particular: the tension
      between providing a caring and supportive institutional environment and ensuring
      that patients are returned to the community when they are ready; the links
      between an acute inpatient facility and its local community; the potential
      significance of the psychiatric hospital as a relatively stable feature in the
      otherwise insecure and unpredictable geographical experience of people with long
      term mental illnesses. We discuss the relevance of these issues for design of new
      psychiatric inpatient facilities.

PMID- 18722153
TI  - Descemet's membrane detachment attributed to the mechanical forces of airbag
      deployment.
AB  - PURPOSE: A patient who developed a Descemet's membrane detachment 3 weeks
      following airbag deployment is reported. CASE REPORT: A hydrogel contact lens
      wearer (extended wear) presented to her primary eye care provider with a painful
      red eye that had been treated with pressure patching the previous day at a
      hospital emergency room. Examination revealed full thickness corneal edema
      localized in the temporal region of the left eye, a corneal infiltrate with an
      overlying epithelial defect, and an anterior chamber reaction with marked
      temporal injection. The patient was referred to a corneal specialist after the
      cornea failed to respond to anti-microbial treatment. Probing of the history
      revealed that the patient had recently sustained an automobile accident in which
      the front air bags had deployed. Confocal microscopy revealed that Descemet's
      membrane was detached, presumably secondary to the mechanical forces of airbag
      deployment. The patient recovered normal vision after 3 weeks of topical therapy
      and ultimately returned to successful contact lens wear. DISCUSSION: Although
      Descemet's membrane detachment is an uncommon complication of airbag deployment,
      it is important to exclude this possibility because delayed diagnosis and
      treatment may compromise the corneal endothelium, predispose the cornea to
      chronic edema, and result in permanent vision loss. An awareness of the spectrum
      of injuries resulting from airbag deployment should facilitate early diagnosis
      and treatment, particularly in situations where the etiology of the presenting
      eye condition is not readily apparent.

PMID- 18722154
TI  - Vibrational spectra of phenyltriethoxysilane, phenyltrimethoxysilane and their
      sol-gels.
AB  - Raman and infrared spectra of phenyltriethoxysilane and phenyltrimethoxysilane
      have been recorded. These silane coupling agents (SCAs) have been used as
      precursors to prepare sol-gels using acid or base as catalyst under different
      solution conditions. From the vibrational spectroscopic identification, it was
      found that the major sol-gel products obtained from different catalysts and
      different solvents were essentially the same. Vibrational assignments for the
      SCAs, sol-gel and xerogel have been made based on the group frequencies, the
      spectral variation collected at different physical and chemical states and the
      previous spectroscopic studies of similar molecules. The compositions of xerogels
      after thermal treatments at different temperatures have been analyzed and
      identified by using infrared spectroscopic method along with thermal gravimetric
      analysis. Results from the experimental treatments for the xerogels indicated
      that the xerogel baking at 118 degrees C served to evaporate the sample moisture,
      the curing at 225 degrees C helped to complete the condensation reaction, and the
      treatment at 600 degrees C caused the decomposition of the organic group but the
      siloxane net-work remained essentially unchanged.

PMID- 18722155
TI  - Voltammetric and spectroscopic studies on binding of antitumor Morin, Morin-Cu
      complex and Morin-beta-cyclodextrin with DNA.
AB  - A systematic comparative study of the binding of antitumor Morin and its
      complexes with DNA has been investigated in the Britton-Robison (BR) buffer
      solutions using voltammetric and spectroscopic methods. The results show that
      Morin molecule, acting as an intercalator, is inserted into the cavity of the
      beta-cyclodextrin (beta-CD) as well as into the base stacking domain of the DNA
      double helix. The interaction of Morin-Cu complex or the inclusion complex of
      Morin-beta-CD with ds-DNA causes hypochromism in the absorption spectra, along
      with pronounced changes in the electrochemical behavior of the Morin complexes.
      An isobestic point and a new spectrum band appeared indicating the formation of
      the new system of Morin-Cu-DNA at lambda(m)=391 nm and Morin-beta-CD-DNA at
      lambda(m)=375 nm. The intercalation of Morin-Cu and Morin-beta-CD complexes with
      DNA produces an electrochemically inactive supramolecular complex. The binding
      constants were calculated from the increase of the solubility, the strong
      hypochromism, and the decrease in peak current of Morin and its complexes upon
      the addition of the host molecules. Calculation of the thermodynamic parameters
      of the interaction of the inclusion complex of Morin-beta-CD with DNA, including
      Gibbs free energy change, Helmholz free energy and entropy change shows that the
      complexation is a spontaneous process of association.

PMID- 18722156
TI  - Synthesis and spectroscopic studies on complexes of N,N'-bis-(2
      pyridinecarboxaldimine)-1,8-diaminonaphthalene (L); DNA binding studies on Cu(II)
      complex.
AB  - The Schiff base ligand, N,N'-bis-(2-pyridinecarboxaldimine)-1,8
      diaminonaphthalene (L), obtained by the condensation of 2-pyridinecarboxaldehyde
      and 1,8-diaminonaphthalene, has been used to synthesize the mononuclear complexes
      of the type [MLCl(2)] [M=Co(II), Ni(II), Cu(II) and Zn(II)]. The newly
      synthesized ligand (L) and its complexes have been characterized on the basis of
      results of elemental analysis, molar conductance, magnetic susceptibility
      measurements, Job's method and spectroscopic studies viz., FT-IR, Mass, (1)H and
      (13)C NMR. The UV-vis and magnetic moment data revealed an octahedral geometry
      around Co(II), Ni(II) and Cu(II) ions and conductivity data show a non
      electrolytic nature of the complexes. Absorption and fluorescence spectroscopic
      studies support that Cu(II) complex exhibits significant binding to calf thymus
      DNA.

PMID- 18722157
TI  - Tick bites in a Lyme borreliosis highly endemic area in Switzerland.
AB  - The duration of tick feeding is an important indicator to evaluate the risk of
      Borrelia burgdorferi sensu lato transmission, which increases considerably with
      the blood meal duration. This blood meal duration may be estimated from scutal
      index, the ratio between body length (idiosoma) and scutum width. For the
      estimation of blood meal duration in Ixodes ricinus, nymphal and adult female
      ticks were detached at predetermined intervals (24, 48, 72, and 96h) from
      laboratory mice and rabbits and their scutal index calculated. From this, non
      linear regression equations were developed to determine the duration of
      attachment for nymphal and adult female I. ricinus ticks. As part of an
      epidemiological study addressing the risk of subclinical (seroconversion) and
      clinical infections after a tick bite in the Neuchatel area (Switzerland) over 3
      years (2003-2005), duration of tick attachment and anatomical site of bites
      collected on participants as well as seasonal distribution of tick bites were
      studied. Tick attachment duration was estimated in all ticks collected during
      this study (n=261). Nymphs were attached for a mean (+/- standard error, SE) of
      31.6h (+/-2.6) and females for a mean (+/-SE) of 29.6h (+/-3.2). Most nymphs were
      removed after 24h of blood meal whereas most females were removed before 24h.
      Legs were the major anatomical sites of bites for women (40.7%), men (44.4%), and
      almost all age classes. Only children <10 years old were bitten more frequently
      on the head (41.2%) and on the neck (38.5%) than participants >10 years. The
      majority of tick bites were recorded from May to July during the 3 years.
      Attachment sites can influence the discovery of ticks, hence the duration of the
      tick bite. A detailed body examination after each outing in forest and an early
      withdrawal of an attached tick is an effective way to prevent Lyme borreliosis.

PMID- 18722158
TI  - Diagnostic and prognostic significance of plasma N-terminal-pro-brain natriuretic
      peptide in decompensated heart failure with preserved ejection fraction.
AB  - BACKGROUND: Preserved ventricular function is increasingly recognised in CHF.
      Although, NTpro-BNP is a well-established diagnostic marker in heart failure with
      impaired EF, its significance in heart failure with preserved EF is unclear. NT
      pro-BNP is secreted from the ventricular wall and plasma levels correlate to
      ventricular function. This study sought to determine the diagnostic and
      prognostic significance of plasma NTpro-BNP in patients with preserved EF heart
      failure. METHODS: We recruited 133 consecutive patients with decompensated HF.
      The primary end point was death or hospital readmission. RESULTS: Median (IQR)
      NTpro-BNP level at admission was elevated at 5043 ng/L (2693-10,784) and was
      significantly lower in preserved EF, 3569 ng/L (1707-6340) than in impaired EF,
      6363 ng/L (3648-13,250) (P=0.001). Eight (6%) and 19 (14%) patients died after 1
      and 6 months, respectively. In a regression analysis, worsening of NTpro-BNP
      levels after treatment was not predictive of mortality in heart failure with
      preserved EF (P=0.83). Levels at discharge correlated with readmission rates at 6
      months in both groups, i.e. impaired (P=0.03) and preserved EF (P=0.02).
      CONCLUSION: NTpro-BNP is a reliable diagnostic marker of decompensation. However,
      in preserved EF heart failure, the plasma levels are significantly lower and a
      worsening in levels after treatment is not predictive of mortality.

PMID- 18722159
TI  - Establishment of an Australian National Genetic Heart Disease Registry.
AB  - A National Genetic Heart Disease Registry has recently been established, with the
      aim to enroll every family in Australia with a genetically determined
      cardiomyopathy or primary arrhythmic disorder. The Registry seeks to further our
      understanding of the impact and burden of disease in this population; increase
      awareness and provide education to health professionals and families; and
      establish a large cardiac genetic cohort as a resource for approved research
      studies. The Registry is currently recruiting families with inherited
      cardiomyopathies (e.g. hypertrophic cardiomyopathy) and primary arrhythmogenic
      disorders (e.g. long QT syndrome), with scope to expand this in the future.
      Affected individuals, as well as their first-degree (at-risk) family members are
      eligible to enroll. Participants are currently being recruited from cardiac
      genetics clinics in approved recruitment sites and hope to expand to other
      Australian centres including general cardiology practice in the future. A
      significant focus of the Registry is to improve understanding and create
      awareness of inherited heart diseases, which includes ensuring families are aware
      of genetic testing options and current clinical screening recommendations for at
      risk family members. A Registry Advisory Committee has been established under the
      NHMRC Guidelines, and includes a representative from each major recruitment
      centre. This committee approves all decisions relating to the Registry including
      approval of research studies. A National Genetic Heart Disease Registry will
      provide a valuable resource to further our knowledge of the clinical and genetic
      aspects of these diseases. Since most of the current data about the prevalence,
      natural history and outcomes of genetic heart diseases has emanated from the
      United States and Europe, characterising these Australian populations will be of
      significant benefit, allowing for more informed and specific health care planning
      and resource provision.

PMID- 18722160
TI  - Maintenance of quality in a small cardiac surgical unit.
AB  - BACKGROUND: The purpose of this study was to evaluate the outcome of cardiac
      surgery at Allamanda Hospital which is a small private hospital carrying out less
      than 100 operations per year. METHODS: Data on patients undergoing cardiac
      surgery since 2002 were prospectively entered into a database. An analysis of
      this data is presented and compared with national and international benchmarks
      for results from larger national and international cardiac surgery units.
      RESULTS: From October 2002 to March 2007, there were 360 patients who underwent
      cardiac surgery in a small private cardiothoracic surgical unit (average of 80
      patients per year). The average logistic EuroSCORE, Cleveland Clinic and
      Parsonnet Scores for the patients were 13%, 5.7 and 13.4, respectively. The mean
      logistic EuroSCORE observed in this study of 13% was substantially higher than
      those of other published series and institutions. The Allamanda results were
      compared with those from the European database (EuroSCORE), the STS and the
      Victorian National Cardiac Surgery Database. The overall observed mortality at
      Allamanda of 7.5% was lower than predicted by the mean logistic EuroSCORE of 13%.
      In comparison with the Victorian database, there was no significant difference in
      mortality for low-risk (additive EuroSCORE 0-3) and medium-risk (4-6) groups.
      Patients in the high-risk group with additive EuroSCOREs>or=7 were similarly
      divided into categories of three additive EuroSCOREs. There was no significant
      difference in any of the categories in the high-risk group. There was a greater
      proportion of high-risk (additive EuroSCORE>or=7) patients in the Allamanda
      series (P<0.0001). Patients in the Allamanda series were older (mean age 70.1)
      than the other published series (P<0.0001). The mean logistic EuroSCORE for the
      mortality group was 35.9+/-29.4% (6.4-65.3%). CONCLUSION: Low volume cardiac
      surgery can be undertaken safely in a small Australian private cardiothoracic
      unit with acceptable results. The trend towards improved outcomes for high-risk
      patients in larger institutions suggests that such patients undergoing elective
      procedures should be given the option of doing so in a larger centre. Ongoing
      quality assurance programs are equally important for large and small cardiac
      surgical units with participation in a national or international cardiac surgery
      database.

PMID- 18722161
TI  - Evaluation of clinical teaching models for nursing practice.
AB  - Clinical placements provide opportunities for student nurses to learn
      experientially. To create a constructive learning environment staff need to be
      friendly, approachable, available and willing to teach. There must be adequate
      opportunities for students to develop confidence and competence in clinical
      skills with a focus on student learning needs rather than service needs of
      facilities. A popular model for clinical teaching of nursing students is the
      preceptor model. This model involves a student working under the supervision of
      individual registered nurses who are part of the clinical staff. This model was
      failing to meet students' needs in acute nursing practice areas, largely due to
      Registered Nurse staff shortages and demanding workloads. The students'
      evaluations led to the trial of a 'cluster' or group model of eight students,
      with a clinical facilitator who is paid by the university, in each acute nursing
      ward. Evaluation of twenty nursing students' perceptions of their acute nursing
      practice clinical placements was conducted using a mixed method approach to
      evaluate the two models of student supervision. Results indicate that the
      students prefer small groups with the clinical facilitator in one area. Thus
      evaluation and feedback from students and the perceptions of their clinical
      placement is essential.

PMID- 18722162
TI  - Immunoadsorption method using immunoglobulin Adsopak in adult cases with ITP
      resistant to splenectomy and other medical therapies.
AB  - BACKGROUND: Despite all medical therapies and splenectomy performed, severe life
      threatening thrombocytopenia persists in many adult patients. AIM OF THE STUDY:
      To evaluate the efficiency of Immunoglobulin Adsopak immunoadsorption method in
      eliminating circulating immunocomplexes and IgG from plasma in these cases.
      METHODS: The method of POCARD Ig-Adsopak Wide Spectrum was applied to four cases
      with severe thrombocytopenia (< or =20.000/microL) by treating with a daily
      plasma of 0.25-2 L for 6 days. Platelet counts were recorded at the beginning and
      during administration of the method. For long-term effects, the cases were called
      for monthly controls during which platelet counts were measured. RESULTS:
      Platelet counts of four cases started to increase on average as of the first day.
      On Day 11, the platelet count reached 50.000/microL. On the following days (Day
      17), platelet count was recorded as 90.000/microL. Cases were followed up for a
      mean of 2 years. At the end of 2 years, mean platelet count of the patients was
      210.000 (175.000-265.000) microL. CONCLUSION: In adult cases who do not respond
      to surgical and medical therapy, including splenectomy, the results obtained from
      the therapy using the method of Immunoadsorption with Immunoglobulin Adsopak are
      promising both in short and long-term follow up.

PMID- 18722163
TI  - Commentary on the International Course on Practice and Quality Assurance in
      Transfusion Medicine in Norway, May 2007.

PMID- 18722164
TI  - Best Practice and Research Clinical Obstetrics and Gynaecology. Preface.

PMID- 18722165
TI  - Specific inflammatory condition in nucleus tractus solitarii of the SHR: novel
      insight for neurogenic hypertension?
AB  - Human essential hypertension is a complex polygenic trait with underlying genetic
      components that remain unknown. Since the brainstem structure--the nucleus of the
      solitary tract (NTS)--is a pivotal region for regulating the set-point of
      arterial pressure, we proposed a role for it in the development of primary
      hypertension. Using microarray and real-time RT-PCR, we have recently identified
      that some pro-inflammatory molecules, such as junctional adhesion molecule-1 (JAM
      1; a leukocyte/platelet adhesion molecule), were over expressed in endothelial
      cells in the NTS of an animal model of human essential hypertension--the
      spontaneously hypertensive rat (SHR) compared to normotensive Wistar Kyoto rats
      (WKY). Adenoviral mediated over expression of JAM-1 in NTS of WKY rats produced
      both hypertension and localized leukocyte adherence to the microvasculature. With
      a known effect of leukocyte adhesion causing cytokine release, we predicted
      differences in the level of gene expression of cytokines in the NTS of SHR
      relative to WKY. Gene expression of monocyte chemoattractant protein-1 (MCP-1)
      was higher in the NTS of SHR while inter-leukin-6 (IL-6) was lower in the NTS of
      SHR compared to the WKY. Because both inflammatory molecules are known to affect
      neural functions, our data suggest that the microvasculature of NTS of the SHR
      exhibits a specific inflammatory state. We propose a new hypothesis that as a
      consequence of enhanced expression of leukocyte adhesion molecules within the
      microvasculature of NTS there is a specific inflammatory response that leads to
      cardiovascular autonomic dysfunction contributing to neurogenic hypertension.

PMID- 18722166
TI  - Physical, chemical and in vitro biological profile of chitosan hybrid membrane as
      a function of organosiloxane concentration.
AB  - We attempted to prepare chitosan-silicate hybrid for use in a medical application
      and evaluated the physico-chemical properties and osteocompatibility of the
      hybrids as a function of gamma-glycidoxypropyltrimethoxysilane (GPTMS)
      concentration. Chitosan-silicate hybrids were synthesized using GPTMS as the
      reagent for cross-linking of the chitosan chains. Fourier transform infrared
      spectroscopy, (29)Si CP-MAS NMR spectroscopy and the ninhydrin assay were used to
      analyze the structures of the hybrids, and stress-strain curves were recorded to
      estimate their Young's modulus. The swelling ability, contact angle and
      cytocompatibility of the hybrids were investigated as a function of the GPTMS
      concentration. A certain fraction of GPTMS in each hybrid was linked at the epoxy
      group to the amino group of chitosan, which was associated with the change in the
      methoxysilane group of GPTMS due to hybridization. The cross-linking density was
      around 80% regardless of the volume of GPTMS. As the content of GPTMS increased,
      the water uptake decreased and the hydrophilicity of the hybrids increased except
      when the content exceeded amolar ratio of 1.5, when it caused a decrease. The
      values of the mechanical parameters assessed indicated that significant
      stiffening of the hybrids was obtained by the addition of GPTMS. The adhesion and
      proliferation of the MG63 osteoblast cells cultured on the chitosan-GPTMS hybrid
      surface were improved compared to those on the chitosan membrane, regardless of
      the GPTMS concentration. Moreover, human bone marrow osteoblast cells
      proliferated on the chitosan-GPTMS hybrid surface and formed a fibrillar
      extracellular matrix with numerous calcium phosphate globular structures, both in
      the presence and in the absence of dexamethasone. Therefore, the chitosan-GPTMS
      hybrids are promising candidates for basic materials that can promote bone
      regeneration because of their controllable composition (chitosan/GPTMS ratio).

PMID- 18722167
TI  - Biocompatibility and osteogenicity of degradable Ca-deficient hydroxyapatite
      scaffolds from calcium phosphate cement for bone tissue engineering.
AB  - Ca-deficient hydroxyapatite (CDHA) porous scaffolds were successfully fabricated
      from calcium phosphate cement (CPC) by a particle-leaching method. The
      morphology, porosity and mechanical strength as well as degradation of the
      scaffolds were characterized. The results showed that the CDHA scaffolds with a
      porosity of 81% showed open macropores with pore sizes of 400-500mum. Thirty-six
      per cent of these CDHA scaffolds were degraded after 12 weeks in Tris-HCl
      solution. Mesenchymal stem cells (MSCs) were cultured, expanded and seeded on the
      scaffolds, and the proliferation and differentiation of MSCs into osteoblastic
      phenotype were determined using MTT assay, alkaline phosphatase activity and
      scanning electron microscopy. The results revealed that the CDHA scaffolds were
      biocompatible and had no negative effects on the MSCs in vitro. The in vivo
      biocompatibility and osteogenicity of the scaffolds were investigated. Both CDHA
      scaffolds and MSC/scaffold constructs were implanted in rabbit mandibles and
      studied histologically. The results showed that CDHA scaffolds exhibited good
      biocompatibility and osteoconductivity. Moreover, the introduction of MSCs into
      the scaffolds dramatically enhanced the efficiency of new bone formation,
      especially at the initial stage after implantation (from 2 to 4 weeks). However,
      the CDHA scaffolds showed as good biocompatibility and osteogenicity as the
      hybrid ones at 8 weeks. These results indicate that the CDHA scaffolds fulfill
      the basic requirements of bone tissue engineering scaffold.

PMID- 18722168
TI  - The use of flat punch indentation to determine the viscoelastic properties in the
      time and frequency domains of a soft layer bonded to a rigid substrate.
AB  - This paper reports a computational study of the indentation of a flat punch into
      a compressible elastic layer (with Poisson's ratio varying from 0 to 0.49) bonded
      to a rigid substrate. Based on the computational results and using Sneddon's
      solution [Sneddon IN. The relation between load and penetration in the
      axisymmetric Boussinesq problem for a punch of arbitrary profile. Int J Eng Sci
      1965;3:47] and the asymptotic solution [Jaffar MJ. A general solution to the
      axisymmetric frictional contact problem of a thin bonded elastic layer. Proc Inst
      Mech Eng C 1997;211:549; Yang FQ. Asymptotic solution to axisymmetric indentation
      of a compressible elastic thin film. Thin Solid Films 2006;515:2274] as the two
      limits, a simple expression of the load-depth curve valid for an arbitrary ratio
      of the indenter radius to the thickness of the layer is obtained. Further, a
      correlation between indentation load and depth for a rigid flat punch indenting
      into linearly viscoelastic layers bonded to a rigid substrate is proposed by
      using the correspondence principle. Several procedures are suggested based on the
      results reported in this study to determine the viscoelastic properties of the
      layer in the time or frequency domains. The findings are verified by numerical
      examples. The results may facilitate the use of depth-sensing indentation tests
      to characterize the mechanical properties of polymeric films or functional
      coatings on hard substrates, and some biological materials, e.g. articular
      cartilage.

PMID- 18722169
TI  - Plexiform neurofibroma of the finger.

PMID- 18722170
TI  - Fascia lata graft for nasal dorsal contouring in rhinoplasty.
AB  - Nasal dorsal irregularities are troublesome for both patient and surgeon,
      especially in patients with thin nasal dorsal skin. Many types of grafts have
      been used for nasal contouring; however, in this article, we report the use of
      fascia lata (FL) graft for dorsal contouring and camouflage in 63 patients who
      underwent rhinoplasty between May 2004 and December 2005. There were 26 male and
      37 female patients, with ages ranging from 18 to 43 years (mean age: 28.7). Of
      the 63 patients, 49 underwent primary rhinoplasty, while 14 were secondary cases.
      An informed consent was obtained from all patients for the use of FL graft. The
      graft was harvested from the right lateral thigh. A simple method was used to
      place the graft over the nasal dorsum. Postoperative follow-up period was between
      14 and 26 months (mean: 20). Clinical evaluation was made by inspection,
      palpation and photographic documentation. In addition, a questionnaire related to
      patient satisfaction and donor-site morbidity was sent to patients 1 year after
      surgery. All patients had satisfactory aesthetic results, and no apparent
      irregularities were observed over the nasal dorsum. The questionnaire results
      showed that all patients, but one, were satisfied with surgery, and were not
      concerned about donor-site scar; however, one patient had a donor-site morbidity.
      This study conclusively shows that TLF graft is a reliable, simple method for
      camouflaging any postoperative dorsal irregularities, particularly in patients
      with thin nasal skin.

PMID- 18722171
TI  - Giant cell reparative granuloma of the orbits, maxillae and mandible.

PMID- 18722173
TI  - Chromosome fusions following telomere loss are mediated by single-strand
      annealing.
AB  - Progressive telomere shortening eventually results in chromosome fusions and
      genome instability as the cell's ability to distinguish chromosome ends from DNA
      double-strand breaks is compromised. In fission yeast, such events frequently
      produce stable survivors with all circular chromosomes. To shed light on the
      repair pathways that mediate chromosome end fusions and generate circular
      chromosomes, we have examined a diverse array of DNA repair factors. We show that
      telomere attrition-induced chromosome fusions are dependent on the fission yeast
      homologs of Rad52, the ERCC1/XPF endonuclease, the single-stranded DNA-binding
      protein RPA, and the Srs2 and Werner/Bloom helicases, but not Ku and ligase 4.
      Consistent with a recombinational mechanism of single-strand annealing, cloned
      junctions map to four of five homology regions in subtelomeric DNA. A comparison
      with telomere uncapping caused by the absence of the double-stranded telomere
      binding protein Taz1 demonstrates that the circumstances and cause of telomere
      dysfunction profoundly affect which DNA repair pathway is engaged.

PMID- 18722174
TI  - Interaction between antibody-diversification enzyme AID and spliceosome
      associated factor CTNNBL1.
AB  - Activation-induced deaminase (AID) deaminates deoxycytidine residues in
      immunoglobulin genes, triggering antibody diversification. Here, by use of two
      hybrid and coimmunoprecipitation assays, we identify CTNNBL1 (also known as NAP)
      as an AID-specific interactor. Mutants of AID that interfere with CTNNBL1
      interaction yield severely diminished hypermutation and class switching. Targeted
      inactivation of CTNNBL1 in DT40 B cells also considerably diminishes IgV
      diversification. CTNNBL1 is a widely expressed nuclear protein that associates
      with the Prp19 complex of the spliceosome, interacting with its CDC5L component.
      The results, therefore, identify residues in AID involved in its in vivo
      targeting and suggest they might act through interaction with CTNNBL1, giving
      possible insight into the linkage between AID recruitment and target-gene
      transcription.

PMID- 18722172
TI  - Lysine acetylation: codified crosstalk with other posttranslational
      modifications.
AB  - Lysine acetylation has emerged as a major posttranslational modification for
      histones. Crossregulation between this and other modifications is crucial in
      modulating chromatin-based transcriptional control and shaping inheritable
      epigenetic programs. In addition to histones, many other nuclear proteins and
      various cytoplasmic regulators are subject to lysine acetylation. This review
      focuses on recent findings pertinent to acetylation of nonhistone proteins and
      emphasizes how this modification might crosstalk with phosphorylation,
      methylation, ubiquitination, sumoylation, and others to form code-like multisite
      modification programs for dynamic control of cellular signaling under diverse
      conditions.

PMID- 18722175
TI  - A biochemically defined system for coding joint formation in V(D)J recombination.
AB  - V(D)J recombination is one of the most complex DNA transactions in biology. The
      RAG complex makes double-stranded breaks adjacent to signal sequences and creates
      hairpin coding ends. Here, we find that the kinase activity of the Artemis:DNA
      PKcs complex can be activated by hairpin DNA ends in cis, thereby allowing the
      hairpins to be nicked and then to undergo processing and joining by nonhomologous
      DNA end joining. Based on these insights, we have reconstituted many aspects of
      the antigen receptor diversification of V(D)J recombination by using 13 highly
      purified polypeptides, thereby permitting variable domain exon assembly by using
      this fully defined system in accord with the 12/23 rule for this process. The
      features of the recombination sites created by this system include all of the
      features observed in vivo (nucleolytic resection, P nucleotides, and N nucleotide
      addition), indicating that most, if not all, of the end modification enzymes have
      been identified.

PMID- 18722176
TI  - Molecular mechanism of sequence-directed DNA loading and translocation by FtsK.
AB  - Dimeric circular chromosomes, formed by recombination between monomer sisters,
      cannot be segregated to daughter cells at cell division. XerCD site-specific
      recombination at the Escherichia coli dif site converts these dimers to monomers
      in a reaction that requires the DNA translocase FtsK. Short DNA sequences, KOPS
      (GGGNAGGG), which are polarized toward dif in the chromosome, direct FtsK
      translocation. FtsK interacts with KOPS through a C-terminal winged helix domain
      gamma. The crystal structure of three FtsKgamma domains bound to 8 bp KOPS DNA
      demonstrates how three gamma domains recognize KOPS. Using covalently linked
      dimers of FtsK, we infer that three gamma domains per hexamer are sufficient to
      recognize KOPS and load FtsK and subsequently activate recombination at dif.
      During translocation, FtsK fails to recognize an inverted KOPS sequence.
      Therefore, we propose that KOPS act solely as a loading site for FtsK, resulting
      in a unidirectionally oriented hexameric motor upon DNA.

PMID- 18722177
TI  - CCAR1, a key regulator of mediator complex recruitment to nuclear receptor
      transcription complexes.
AB  - DNA-bound transcription factors recruit many coactivator proteins to remodel
      chromatin and activate transcription. The Mediator complex is believed to recruit
      RNA polymerase II to most protein-encoding genes. It is generally assumed that
      interaction of Mediator subunits with DNA-binding transcription factors is
      responsible for Mediator recruitment to promoters. However, we report here that
      Mediator recruitment by nuclear receptors (NR) requires a coactivator protein,
      CCAR1 (cell-cycle and apoptosis regulator 1). CCAR1 associates with components of
      the Mediator and p160 coactivator complexes and is recruited to endogenous NR
      target genes in response to the appropriate hormone. Reduction of endogenous
      CCAR1 levels inhibited hormone-induced expression of endogenous NR target genes,
      hormone-induced recruitment of Mediator components and RNA polymerase II to
      target gene promoters, and estrogen-dependent growth of breast cancer cells.
      Thus, CCAR1 regulates expression of key proliferation-inducing genes. CCAR1 also
      functions as a p53 coactivator, suggesting a broader role in transcriptional
      regulation.

PMID- 18722179
TI  - Dominant and redundant functions of TFIID involved in the regulation of hepatic
      genes.
AB  - To study the in vivo role of TFIID in the transcriptional regulation of hepatic
      genes, we generated mice with liver-specific disruption of the TAF10 gene.
      Inactivation of TAF10 in hepatocytes resulted in the dissociation of TFIID into
      individual components. This correlated with the downregulation of most hepatocyte
      specific genes during embryonic life and a defect in liver organogenesis.
      Unexpectedly, however, the transcription of less than 5% of active genes was
      affected by TAF10 inactivation and TFIID disassembly in adult liver. The extent
      of changes in transcription of the affected genes was dependent on the timing of
      their activation during liver development, relative to that of TAF10
      inactivation. Furthermore, TFIID dissociation from promoters leads to the re
      expression of several postnatally silenced hepatic genes. Promoter occupancy
      analyses, combined with expression profiling, demonstrate that TFIID is required
      for the initial activation or postnatal repression of genes, while it is
      dispensable for maintaining ongoing transcription.

PMID- 18722178
TI  - Genome-wide analysis of the H3K4 histone demethylase RBP2 reveals a
      transcriptional program controlling differentiation.
AB  - Retinoblastoma protein (pRB) mediates cell-cycle withdrawal and differentiation
      by interacting with a variety of proteins. RB-Binding Protein 2 (RBP2) has been
      shown to be a key effector. We sought to determine transcriptional regulation by
      RBP2 genome-wide by using location analysis and gene expression profiling
      experiments. We describe that RBP2 shows high correlation with the presence of
      H3K4me3 and its target genes are separated into two functionally distinct
      classes: differentiation-independent and differentiation-dependent genes. The
      former class is enriched by genes that encode mitochondrial proteins, while the
      latter is represented by cell-cycle genes. We demonstrate the role of RBP2 in
      mitochondrial biogenesis, which involves regulation of H3K4me3-modified
      nucleosomes. Analysis of expression changes upon RBP2 depletion depicted genes
      with a signature of differentiation control, analogous to the changes seen upon
      reintroduction of pRB. We conclude that, during differentiation, RBP2 exerts
      inhibitory effects on multiple genes through direct interaction with their
      promoters.

PMID- 18722180
TI  - The unique N terminus of the UbcH10 E2 enzyme controls the threshold for APC
      activation and enhances checkpoint regulation of the APC.
AB  - In vitro, the anaphase-promoting complex (APC) E3 ligase functions with E2
      ubiquitin-conjugating enzymes of the E2-C and Ubc4/5 families to ubiquitinate
      substrates. However, only the use of the E2-C family, notably UbcH10, is
      genetically well validated. Here, we biochemically demonstrate preferential use
      of UbcH10 by the APC, specified by the E2 core domain. Importantly, an additional
      E2-E3 interaction mediated by the N-terminal extension of UbcH10 regulates APC
      activity. Mutating the highly conserved N terminus increases substrate
      ubiquitination and the number of substrate lysines targeted, allows
      ubiquitination of APC substrates lacking their destruction boxes, increases
      resistance to the APC inhibitors Emi1 and BubR1 in vitro, and bypasses the
      spindle checkpoint in vivo. Fusion of the UbcH10 N terminus to UbcH5 restricts
      ubiquitination activity but does not direct specific interactions with the APC.
      Thus, UbcH10 combines a specific E2-E3 interface and regulation via its N
      terminal extension to limit APC activity for substrate selection and checkpoint
      control.

PMID- 18722181
TI  - Bax- or Bak-induced mitochondrial fission can be uncoupled from cytochrome C
      release.
AB  - Bax and Bak promote apoptosis by perturbing the permeability of the mitochondrial
      outer membrane and facilitating the release of cytochrome c by a mechanism that
      is still poorly defined. During apoptosis, Bax and Bak also promote fragmentation
      of the mitochondrial network, possibly by activating the mitochondrial fission
      machinery. It has been proposed that Bax/Bak-induced mitochondrial fission may be
      required for release of cytochrome c from the mitochondrial intermembrane space,
      although this has been a subject of debate. Here we show that Bcl-xL, as well as
      other members of the apoptosis-inhibitory subset of the Bcl-2 family, antagonized
      Bax and/or Bak-induced cytochrome c release but failed to block mitochondrial
      fragmentation associated with Bax/Bak activation. These data suggest that Bax/Bak
      initiated remodeling of mitochondrial networks and cytochrome c release are
      separable events and that Bcl-2 family proteins can influence mitochondrial
      fission-fusion dynamics independent of apoptosis.

PMID- 18722183
TI  - Structure of activated thrombin-activatable fibrinolysis inhibitor, a molecular
      link between coagulation and fibrinolysis.
AB  - Thrombin-activatable fibrinolysis inhibitor (TAFI) is a metallocarboxypeptidase
      (MCP) that links blood coagulation and fibrinolysis. TAFI hampers fibrin-clot
      lysis and is a pharmacological target for the treatment of thrombotic conditions.
      TAFI is transformed through removal of its prodomain by thrombin-thrombomodulin
      into TAFIa, which is intrinsically unstable and has a short half-life in vivo.
      Here we show that purified bovine TAFI activated in the presence of a
      proteinaceous inhibitor renders a stable enzyme-inhibitor complex. Its crystal
      structure reveals that TAFIa conforms to the alpha/beta-hydrolase fold of MCPs
      and displays two unique flexible loops on the molecular surface, accounting for
      structural instability and susceptibility to proteolysis. In addition, point
      mutations reported to enhance protein stability in vivo are mainly located in the
      first loop and in another surface region, which is a potential heparin-binding
      site. The protein inhibitor contacts both the TAFIa active site and an exosite,
      thus contributing to high inhibitory efficiency.

PMID- 18722182
TI  - Caenorhabditis elegans drp-1 and fis-2 regulate distinct cell-death execution
      pathways downstream of ced-3 and independent of ced-9.
AB  - The dynamin family of GTPases regulate mitochondrial fission and fusion processes
      and have been implicated in controlling the release of caspase activators from
      mitochondria during apoptosis. Here we report that profusion genes fzo-1 and eat
      3 or the profission gene drp-1 are not required for apoptosis activation in C.
      elegans. However, minor proapoptotic roles for drp-1 and fis-2, a homolog of
      human Fis1, are revealed in sensitized genetic backgrounds. drp-1 and fis-2
      function independent of one another and the Bcl-2 homolog CED-9 and downstream of
      the CED-3 caspase to promote elimination of mitochondria in dying cells, an event
      that could facilitate cell-death execution. Interestingly, CED-3 can cleave DRP
      1, which appears to be important for DRP-1's proapoptotic function, but not its
      mitochondria fission function. Our findings demonstrate that mitochondria
      dynamics do not regulate apoptosis activation in C. elegans and reveal distinct
      roles for drp-1 and fis-2 as mediators of cell-death execution downstream of
      caspase activation.

PMID- 18722184
TI  - Arabidopsis COP1/SPA1 complex and FHY1/FHY3 associate with distinct
      phosphorylated forms of phytochrome A in balancing light signaling.
AB  - Fine tuning of light signaling is crucial to plant development. Following light
      triggered nuclear translocation, the photoreceptor phytochrome A (phyA) regulates
      gene expression under continuous far-red light and is rapidly destabilized upon
      red light irradiation by E3 ubiquitin ligases, including COP1. Here we provide
      evidence that the light signaling repressors SPA proteins contribute to COP1
      mediated phyA degradation and that a COP1/SPA1 protein complex is tightly
      associated with phyA ubiquitination activity. Furthermore, a phosphorylated phyA
      form accumulates in the nucleus and preferentially associates with the COP1/SPA1
      complex. In contrast, underphosphorylated phyA predominantly associates with the
      phyA-signaling intermediates FHY3 and FHY1. However, COP1 associates with
      underphosphorylated phyA in the absence of FHY3 or FHY1, suggesting that phyA
      associations with FHY3 and FHY1 protect underphosphorylated phyA from being
      recognized by the COP1/SPA complex. We propose that light-induced phyA
      phosphorylation acts as a switch controlling differential interactions of the
      photoreceptor with signal propagation or attenuation machineries.

PMID- 18722185
TI  - Introduction to ACCORD-PMI: the Advisory Council on Care Optimization to Reduce
      Death Post-MI.

PMID- 18722186
TI  - Assessment and key targets for therapy in the post-myocardial infarction patient
      with left ventricular dysfunction.
AB  - In the post-myocardial infarction (MI) patient with coronary artery disease (CAD)
      and left ventricular dysfunction (LVD), ischemia and adverse remodeling hinder
      myocardial performance and increase electrical instability. Collectively, the
      coronary arteries, myocardium, and conduction system represent the principal
      pathophysiologic targets in MI complicated by LVD. Consequently, an accurate
      assessment of disease severity in these targets is essential for the design of an
      effective therapeutic program. This review describes the current modalities for
      assessing the key pathophysiologic targets in post-MI patients with LVD and the
      effects of systemic factors on cardiac disease severity.

PMID- 18722187
TI  - Risk stratification and prognostic factors in the post-myocardial infarction
      patient.
AB  - Among the 5 million patients presenting to emergency departments with chest pain
      each year in the United States, approximately 1 million are diagnosed with
      myocardial infarction (MI). Physicians have the difficult task of making
      decisions regarding admission and treatment and identifying patients at high risk
      for adverse outcomes, such as early mortality, left ventricular dysfunction
      (LVD), and heart failure. Several measures can be implemented in the process of
      risk assessment, including clinical judgment, electrocardiographic and
      echocardiographic findings, and the presence of biomarkers. Biomarkers--which can
      be classified as antecedent, screening, diagnostic, staging, or prognostic--may
      help identify the subset of patients who need early intervention and/or intensive
      therapy. Using a multimarker strategy that combines a marker of hemodynamic
      stress (brain natriuretic peptide) or of inflammation (C-reactive protein) with a
      marker of necrosis (cardiac troponin) may help to risk-stratify patients, guide
      treatment, and optimize admission and discharge decisions. This article discusses
      the potential benefits of risk assessment tools in the management of post-MI
      patients with LVD.

PMID- 18722188
TI  - Pharmacologic therapies across the continuum of left ventricular dysfunction.
AB  - Neurohormonal activation and increased sympathetic stimulation are among the
      factors that have been linked to the development and progression of left
      ventricular dysfunction (LVD) and heart failure (HF) in post-myocardial
      infarction (MI) patients. Various available pharmacologic therapies can target
      these factors and improve many aspects of the disease, depending on the degree of
      LVD. The American College of Cardiology/American Heart Association (ACC/AHA)
      guidelines recommend angiotensin-converting enzyme inhibitors, angiotensin
      receptor blockers, beta-blockers, and aldosterone antagonists because of their
      proven favorable effects on symptoms, left ventricular function, cardiac
      remodeling, hospitalization rates, and survival. However, they are not being used
      in over two thirds of patients with post-MI LVD. This review illustrates the
      impact of these therapies on post-MI LVD patients using evidence from multiple
      clinical trials. In addition, current and emerging treatments for acute
      decompensated HF will be outlined.

PMID- 18722189
TI  - Device therapies in the post-myocardial infarction patient with left ventricular
      dysfunction.
AB  - The post-myocardial infarction (MI) patient with left ventricular dysfunction
      (LVD) is at risk for ventricular arrhythmias resulting in sudden cardiac death.
      In high-risk post-MI patients with a depressed left ventricular ejection
      fraction, prophylactic implantable cardioverter defibrillators (ICDs) may
      significantly improve survival. These benefits are in addition to those of
      optimal pharmacologic therapy, and ICD therapy should be considered the standard
      of care in these patients. Recent device trials have demonstrated the benefits of
      prophylactic ICD placement in patients who have been selected based on post-MI
      left ventricular systolic dysfunction alone. In addition, cardiac
      resynchronization therapy can improve the quality of life beyond that achievable
      with drug therapy alone and should be considered in patients with symptomatic
      heart failure with QRS prolongation. Further risk stratification studies of post
      MI LVD patients will allow ICD therapy to be applied in a more cost-effective
      manner.

PMID- 18722190
TI  - Percutaneous coronary intervention for myocardial infarction with left
      ventricular dysfunction.
AB  - Patients who have had a myocardial infarction (MI) are at high risk for
      developing left ventricular dysfunction (LVD), which predisposes them to heart
      failure and is associated with an increased mortality risk. Early coronary
      revascularization, either with percutaneous coronary intervention or coronary
      artery bypass graft surgery, plays an important role in the preservation and
      restoration of left ventricular function after MI. This article discusses the
      effects of primary and nonemergent percutaneous coronary revascularization
      procedures on survival, left ventricular function, and the occurrence of
      complications, such as recurrent MI and stroke, compared with the effects of
      thrombolytic therapy. In addition, this article describes rescue
      revascularization procedures for patients who failed thrombolysis and those
      presenting relatively late or with negative electrocardiographic findings.
      Advanced interventional techniques, such as percutaneous ventricular assist
      devices and bioabsorbable stents, are very promising and may potentially help
      improve the outcomes of post-MI patients with LVD; however, the use of these
      techniques requires further validation.

PMID- 18722191
TI  - Surgical therapies for post-myocardial infarction patients.
AB  - Occasionally, high-risk patients in the post-myocardial infarction (MI) period
      require surgical intervention for stabilization and/or revascularization. In a
      meta-analysis involving 3,088 patients with ischemic heart disease,
      revascularization was associated with nearly an 80% reduction in the risk of
      death. Coronary artery bypass graft (CABG) surgery is commonly performed in post
      MI patients and is associated with more favorable outcomes than medical therapy.
      However, several factors have to be considered in proper patient selection for
      CABG, such as the left ventricular ejection fraction (LVEF), severity of heart
      failure (HF), and myocardial viability. The ongoing Surgical Treatment for
      Ischemic Heart Failure (STICH) trial will assess the benefits of CABG in patients
      with both a low LVEF and HF. Unstable post-MI patients who fail revascularization
      can be managed via mechanical circulatory support devices or pumps. These options
      significantly improve hemodynamic parameters. In addition, other surgical
      techniques, such as mitral valve repair, ventricular reconstruction surgery, and
      atrial fibrillation ablation, are being evaluated in patients with ischemic heart
      disease.

PMID- 18722192
TI  - Implementing critical pathways and a multidisciplinary team approach to
      cardiovascular disease management.
AB  - According to several medical registries, there is a need to improve the care of
      post-myocardial infarction (MI) patients, especially those with left ventricular
      dysfunction (LVD) and heart failure. This can potentially be achieved by
      implementing disease management programs, which include critical pathways,
      patient education, and multidisciplinary hospital teams. Currently, algorithms
      for critical pathways, including discharge processes, are lacking for post-MI LVD
      patients. Such schemes can increase the use of evidence-based medicines proved to
      reduce mortality. Educational programs are aimed at increasing patients'
      awareness of their condition, promoting medication compliance, and encouraging
      the adoption of healthy behaviors; such programs have been shown to be effective
      in improving outcomes of post-MI LVD patients. Reductions in all-cause
      hospitalizations and medical costs as well as improved survival rates have been
      observed when a multidisciplinary team (a nurse, a pharmacist, and a hospitalist)
      is engaged in patient care. In addition, the use of the "pay for performance"
      method, which can be advantageous for patients, physicians, and hospitals, may
      potentially improve the care of post-MI patients with LVD.

PMID- 18722193
TI  - Directions for research in the post-myocardial infarction patient with left
      ventricular dysfunction.

PMID- 18722194
TI  - Chiropractic and public health: current state and future vision.
AB  - This article provides an overview of primary chiropractic issues as they relate
      to public health. This collaborative summary documents the chiropractic
      profession's current involvement in public health, reflects on past barriers that
      may have prevented full participation within the public health movement, and
      summarizes the relationship of current chiropractic and public health topics.
      Topics discussed include how the chiropractic profession participates in
      preventive health services, health promotion, immunization, geriatrics, health
      care in a military environment, and interdisciplinary care.

PMID- 18722195
TI  - Adherence to radiography guidelines for low back pain: a survey of chiropractic
      schools worldwide.
AB  - OBJECTIVE: This study describes instruction provided at chiropractic schools
      worldwide on the use of spine radiography and compares instruction with evidence
      based guidelines for low back pain. METHODS: Individuals responsible for
      radiology instruction at accredited chiropractic schools throughout the world
      were contacted and invited to participate in a Web-based survey. The survey
      included questions on the role of conventional radiography in chiropractic
      practice and instruction given to students for its use in patients with acute low
      back pain. RESULTS: Of the 33 chiropractic schools identified worldwide, 32 (97%)
      participated in the survey. Consistent with the guidelines, 25 (78%) respondents
      disagreed that "routine radiography should be used prior to spinal manipulative
      therapy," 29 (91%) disagreed that there "was a role for full spine radiography
      for assessing patients with low back pain," and 29 (91%) disagreed that "oblique
      views should be part of a standard radiographic series for low back pain."
      However, only 14 (44%) respondents concurred with the guidelines and disagreed
      with the statement that there "is a role for radiography in acute low back pain
      in the absence of 'red flags' for serious disease." CONCLUSIONS: This survey
      suggests that many aspects of radiology instruction provided by accredited
      chiropractic schools appear to be evidence based. However, there appears to be a
      disparity between some schools and existing evidence with respect to the role of
      radiography for patients with acute low back pain without "red flags" for serious
      disease. This may contribute to chiropractic overutilization of radiography for
      low back pain.

PMID- 18722196
TI  - Adverse effects of spinal manipulative therapy in children younger than 3 years:
      a retrospective study in a chiropractic teaching clinic.
AB  - OBJECTIVE: The purpose of this study is to identify any adverse effects to
      chiropractic care occurring in the pediatric patient and to evaluate the risk of
      complications arising in the pediatric patient resulting from chiropractic care.
      METHODS: A 3-year retrospective study of pediatric case files from the Anglo
      European College of Chiropractic (AECC) (Bournemouth, England) teaching clinic
      practice in Bournemouth, England. All files (n = 781) of pediatric patients
      younger than 3 years of age were selected manually in sequential order from
      current files stored in the AECC clinic presenting to the AECC clinic during a
      specific period. Most (73.5%) patients presenting were 12 weeks of age or younger
      (n = 574). RESULTS: Six hundred ninety-seven children received a total of 5242
      chiropractic treatments, with 85% of parents reporting an improvement. Seven
      parents reported an adverse effect. There was a reaction rate of approximately 1
      child in 100, or one reaction reported for every 749 treatments. There were no
      serious complications resulting from chiropractic treatment (reactions lasting
      >24 hours or severe enough to require hospital care). CONCLUSION: This study
      shows that for the population studied, chiropractic manipulation produced very
      few adverse effects and was a safe form of therapy in the treatment of patients
      in this age group.

PMID- 18722197
TI  - Ontario chiropractors' knowledge, attitudes, and beliefs about intimate partner
      violence among their patients: a cross-sectional survey.
AB  - OBJECTIVE: This study assessed chiropractors' attitudes, beliefs, knowledge, and
      experience about intimate partner violence (IPV) and identified if any
      differences exist between age groups, sex, and year of graduation of respondents.
      METHODS: Five hundred five Ontario chiropractors were sampled from the Canadian
      Chiropractic Association membership using a randomization program. This study
      used a cross-sectional survey. The sample was mailed an introductory postcard and
      3 subsequent Provider Surveys, demographic forms, and information letters
      depending on nonresponse. The data were analyzed using descriptive statistics,
      Kruskal-Wallis analyses of variance and Mann-Whitney U tests. RESULTS: A response
      rate of 61% was attained. Of the respondents, 88% reported that IPV was rare or
      very rare in their practice. Significant sex differences were identified. Female
      respondents were almost twice as likely to strongly disagree with victim-blaming
      statements and were almost twice as concerned for their safety as male
      chiropractors when broaching the topic with batterers. Older practitioners were
      significantly more likely to inquire about IPV depending on symptoms, blame
      victims, have less fear of offending victims, and have fewer safety concerns.
      Earlier graduates were significantly more likely to inquire about IPV depending
      on clinical presentation but were also more likely to blame victims. CONCLUSIONS:
      Ontario chiropractors have very little experience identifying IPV. Chiropractors
      would benefit from educational programs that would enable them to better identify
      and manage patients experiencing IPV. Sex, age, and experience were important
      modifiers in Ontario chiropractors' perceptions and behaviors regarding IPV among
      their patients.

PMID- 18722198
TI  - Nutrition and youth soccer for childhood overweight: a pilot novel chiropractic
      health education intervention.
AB  - OBJECTIVE: The purpose of this pilot novel chiropractic health education
      intervention was to gather preliminary evidence regarding possible benefits from
      recreational youth soccer and nutrition education in overweight women. A
      secondary purpose was to determine whether some nutrition knowledge is an
      independent predictor of changes in body mass index (BMI). METHODS: A quiz
      developed and validated on separate age and sex appropriate blinded cohorts was
      used on study participants-22 volunteers of 57 eligible fourth-grade, overweight
      female Mississippi public school students. At the beginning of a 5-month study
      period, a 15-minute baseline nutrition intervention, grounded in Social Cognitive
      Theory and based on the United States Department of Agriculture's "My Tips for
      Families" information, was applied in a chiropractic clinic. Subjects were then
      randomized to 2 months of recreational soccer (n = 14) or waiting list control (n
      = 8). RESULTS: No preintervention differences were found in height, weight, BMI,
      or age. Higher follow-up BMI scores were found in both groups, and no significant
      differences between groups were found, possibly because of the small sample sizes
      and the short 8-week soccer intervention period. Gains in nutrition knowledge
      were sustained (P < .002); however, there was no association between nutrition
      knowledge and follow-up BMI (r = -.185; P < .462). CONCLUSIONS: Minimal nutrition
      education alone may be an ineffective intervention for overweight children. The
      study provides an example of how youth soccer may benefit overweight children.

PMID- 18722199
TI  - Is it time for a population health approach to neck pain?
AB  - OBJECTIVE: Neck pain and its associated disorders (NPAD) cause significant health
      burden in the general population and after road traffic and occupational injury.
      Individual-level health care treatments have been well studied, but population
      health approaches to this problem have not. We used a best-evidence synthesis to
      examine population-level approaches to the prevention and control of NPAD.
      METHODS: The systematic review examined studies published between 1980 and 2006
      that addressed the incidence, prevalence, risk factors, prevention, cost,
      assessment and classification, interventions, and course and prognostic factors
      for NPAD. Citations were screened for relevance, scientifically reviewed, and
      synthesized. Valid studies addressing public policies or population-level
      approaches to the prevention and control of NPAD were identified and used in the
      evidence synthesis. RESULTS: Only 8 of the 552 scientifically admissible studies
      were considered relevant to a public or population health approach to preventing
      and controlling the burden of NPAD. For whiplash-associated disorders, active
      head restraints and seat backs were protective in rear-end collisions; insurance
      policies affected the incidence and recovery; government funding of
      multidisciplinary rehabilitation programs did not benefit recovery; and early
      intensive health care delayed recovery. In the workplace, 2 randomized trials
      failed to show any preventive effect for ergonomic interventions or physical
      training and stress management. One study documented the societal cost of neck
      pain. CONCLUSIONS: There is little evidence on which to make public or population
      level recommendations, despite the important public health burden and costs of
      NPAD. Population-level approaches to preventing and controlling NPAD should be
      investigated.

PMID- 18722200
TI  - Chiropractic treatment of pregnancy-related low back pain: a systematic review of
      the evidence.
AB  - OBJECTIVE: This study systematically reviewed the published evidence regarding
      chiropractic care, including spinal manipulation, for pregnancy-related low back
      pain (LBP). METHODS: A multimodal search strategy was conducted, including
      multiple database searches along with reference and journal hand searching.
      Studies were limited to those published in English and in a peer-reviewed journal
      or conference proceeding between January 1982 and July 2007. All study designs
      were considered except single case reports, personal narratives, and qualitative
      designs. Retrieved articles that met the inclusion criteria were rated for
      quality by using a validated and reliable checklist. RESULTS: Six studies met the
      review's inclusion criteria in the form of 1 quasi-experimental single-group
      pretest-posttest design, 4 case series, and 1 cross-sectional case series study;
      their quality scores ranged from 5 to 14 of 27. All of the included studies
      reported positive results for chiropractic care of LBP during pregnancy. Outcome
      measure use between the studies was inconsistent as were descriptions of
      patients, treatments, and treatment schedules. CONCLUSIONS: Results from the 6
      included studies showed that chiropractic care is associated with improved
      outcomes in pregnancy-related LBP. However, the low-to-moderate quality of
      evidence of the included studies preclude any definitive statement as to the
      efficacy of such care because all studies lacked both randomization and control
      groups. Given the relatively common use of chiropractic care during pregnancy,
      there is need for higher quality observational studies and controlled trials to
      determine efficacy.

PMID- 18722201
TI  - Qualitative methods in chiropractic research: one framework for future inquiry.
AB  - Qualitative research holds potential for helping understand core aspects of
      chiropractic. Nevertheless, these methods remain underused in the field. This
      article overviews a qualitative perspective, introduces qualitative methods, and
      offers one possible framework to develop chiropractic research.

PMID- 18722202
TI  - Adverse events following chiropractic care for subjects with neck or low-back
      pain: do the benefits outweigh the risks?
AB  - This synopsis provides an overview of the benign and serious risks associated
      with chiropractic care for subjects with neck or low-back pain. Most adverse
      events associated with spinal manipulation are benign and self-limiting. The
      incidence of severe complications following chiropractic care and manipulation is
      extremely low. The best evidence suggests that chiropractic care is a useful
      therapy for subjects with neck or low-back pain for which the risks of serious
      adverse events should be considered negligible.

PMID- 18722203
TI  - Spinal palpation for lumbar segmental mobility and pain provocation: an
      interexaminer reliability study.
AB  - OBJECTIVE: This study determined the degree of interexaminer reliability using 2
      experienced clinicians performing 3 palpation procedures over the lumbar facet
      joints and sacroiliac joints. METHODS: The sample consisted of 39 patients with
      low back pain who had a recent history of low back pain. Two doctors of
      chiropractic independently examined each of these patients in the prone position
      with 3 different procedures: (1) springing palpation for pain provocation, (2)
      springing palpation for segmental mobility testing, and (3) the prone instability
      test. The doctors were blinded to each other's findings and the patient's
      clinical status, and performed the examinations on the same day. Standard and
      adjusted kappa values were calculated for each test. RESULTS: The kappa values
      for palpation of segmental motion restriction were poor (range, -.20 to .17) and
      in many cases less than chance observation (negative kappa values). The prone
      instability test showed reasonable reliability (kappa = .54), and palpation for
      segmental pain provocation also showed fair to good reliability (kappa range, .21
      to .73). CONCLUSIONS: Palpation methods that are used to provoke pain responses
      are more reliable than palpation methods in which the clinician purports to find
      segmental motion restriction. The prone instability test shows good reliability.

PMID- 18722204
TI  - The impact of muscular variation on the neurodynamic test for the median nerve in
      a healthy population with Langer's axillary arch.
AB  - OBJECTIVE: The neurodynamic test of the median nerve (ULNT1) is frequently used
      to assess the mechanics and physiology of the brachial plexus and median nerve.
      The present study looks for a positive ULNT1 in a healthy population with
      Langer's axillary arch (LAA) and analyzes whether LAA affects the elbow extension
      range of motion (EE-ROM) of the ULNT1. METHOD: Of 640 volunteers screened, 26 LAA
      sides were finally included. Additional history taking revealed "minor symptoms"
      in some subjects. Minor symptoms do not qualify as a disorder because there is no
      interference with daily activities and no medical advice is sought. This study
      investigates whether the ULNT1 can (re)produce minor symptoms or abnormal
      responses in subjects with LAA. The EE-ROM was compared between the subjects'
      left and right side, and the subtraction angle-which is the effect of placing the
      cervical spine in contralateral lateral flexion-was compared between LAA sides
      and controls. RESULTS: Langer's axillary arch sides showed a significant increase
      in the occurrence of minor symptoms and positive ULNT1, but no influence was
      observed on the EE-ROM. CONCLUSIONS: These findings suggest that LAA may be
      capable of transiently provoking the axillary neurovascular bundle. The
      unaffected EE-ROM may be the consequence of a vascular origin of the minor
      symptoms or the consequence of an ulnar nerve/medial cord response to the ULNT1.

PMID- 18722205
TI  - Shoulder tip pain after laparoscopic surgery analgesia by collateral meridian
      acupressure (shiatsu) therapy: a report of 2 cases.
AB  - OBJECTIVES: This article describes 2 cases of collateral meridian acupressure
      (shiatsu) therapy (CMAT) for treatment of shoulder tip pain after laparoscopic
      cholecystectomy (LC). Both cases showed marked pain relief with reduction of skin
      temperature (1 degrees C) of the affected shoulder after CMAT. CLINICAL FEATURES:
      A 32- and a 53-year-old female presented with right shoulder tip pain after LC
      surgery. The repeated dose of intravenous ketorolac 30 mg and meperidine 50 mg
      did not improve the pain. Because of persistent pain and episodes of nausea and
      vomiting after intravenous nonsteroidal anti-inflammatory drugs and opioid
      medications, patients refused to take more analgesics, and we were consulted for
      pain management. INTERVENTION AND OUTCOME: After informed written consent
      obtained, CMAT was performed using acupoints located on the contralateral (left)
      kidney meridian to treat affected (right) shoulder pain. Postoperatively,
      patients' pain intensity was measured using a numeric pain scale. The infrared
      thermography of shoulder tip was obtained before and after the CMAT. Both
      patients reported immediate pain relief after the CMAT, with pain scores
      decreased from 5 to 1 of 10 and 5 to 0 of 10, respectively. Moreover, the local
      skin temperature of affected shoulders were significantly decreased in both
      patients after the CMAT. Similarly, the temperature difference between patients'
      affected and nonpainful shoulders were also significant after the CMAT.
      CONCLUSION: The results of these 2 cases suggest that the CMAT may be effective
      in reducing patients' post-LC shoulder tip pain without medication. An associated
      reduction of skin temperature of the painful shoulder with CMAT warrants further
      investigation.

PMID- 18722208
TI  - Randomized controlled studies and the treatment of middle-ear effusions and
      tonsillar pharyngitis: how random are the studies and what are their limitations?
AB  - OBJECTIVE: To determine the applicability and external validity of randomized
      control studies (RCTs) in the light of patient susceptibilities and
      vulnerabilities to the sequelae of otitis media with effusion (OME) and tonsillar
      pharyngitis (T&A) and the composition of their cohorts. STUDY DESIGN: RCTs for
      OME and T&A were analyzed to determine which intrinsic and extrinsic
      susceptibilities to the otolaryngic disease and its sequelae were included or
      excluded and the composition of the cohort. METHODS: A Medline and a Science
      Direct search were performed for all RCTs concerning OME and T&A through 2007.
      The articles selected to be included in this study are the OME RCTs that reported
      language and/or hearing outcomes and the T&A RCT studies in which the outcome
      measure was infection, alleviation of airway obstruction, and/or quality of life.
      These were analyzed for their inclusion or exclusion of intrinsic and extrinsic
      susceptibilities to the otolaryngic disease and their sequelae and the
      composition of the cohort. The pertinent otolaryngologic literature was assessed
      to determine applicable risk factors. RESULTS: The analysis of the inclusion or
      exclusion of risk factors showed that for OME 0 percent were included and 16
      percent were excluded, and there were no data for 84 percent. The T&A findings
      were similar in that 1 percent of risk factors were included, 8 percent excluded,
      and there were no data for 92 percent. Both the OME and the T&A cohorts data were
      similar in that approximately half of the suitable candidates completed the
      study; 25 percent of the OME and 13 percent of the T&A enrolled subjects were
      either withdrawn or placed into a different experimental group. On the average,
      with data available, it took 4.6 years to recruit the OME sample and 5.5 years to
      recruit the T&A sample. CONCLUSION: The results of RCTs for these conditions are
      only applicable to narrowly defined and highly circumscribed populations. They
      cannot be generalized to the entire patient population because of their limited
      external validity. Future RCT protocols should be designed to control for the
      intrinsic and extrinsic susceptibilities that result in a propensity to acquire
      the disease and/or an exacerbation of the disease's sequelae. These studies would
      determine the most effective strategies for preventing disorders and/or their
      deleterious sequelae.

PMID- 18722209
TI  - A systematic review of the use of intranasal steroids in the treatment of chronic
      rhinosinusitis.
AB  - OBJECTIVE: To determine if intranasal steroids (INS) are useful in the management
      of chronic rhinosinusitis without polyps and chronic rhinosinusitis (CRS) with
      polyps. DATA SOURCES: Studies for inclusion were searched using Medline, EMBASE,
      Cochrane databases, and references of included studies. REVIEW METHODS: Initial
      screening of article titles and abstracts obtained from the literature search was
      performed independently by two reviewers (SAJ and RT) based on the research
      protocol criteria. These articles then underwent a second-stage review. Each
      article was read in detail and discussed by the two reviewers before inclusion in
      the study. RESULTS: The review yielded 13 studies regarding the treatment of
      sinonasal polyps with intranasal steroids. Six of these could be included in the
      meta-analysis. The outcome measure used for meta-analysis was change in polyp
      size from baseline compared between the treatment and control groups. Results
      from both conservative and optimistic selection of treatment effect are positive,
      providing significant improvement in polyp size in the treatment group as
      compared to controls. In the conservative estimate, the mean improvement in polyp
      size score between the treatment and placebo group is 0.43 with a 95% CI of
      [0.25, 0.61]. Of those treatment groups with the largest improvement, the mean
      improvement in polyp size score can go as high as 0.63 with a 95% CI of [0.43,
      0.82]. CONCLUSION: Intranasal steroids are beneficial in the treatment of chronic
      rhinosinusitis with sinonasal polyps. Further studies looking at the use of INS
      in the treatment of CRS without polyps are warranted.

PMID- 18722210
TI  - Pediatric otolaryngologists' actions regarding secondhand smoke exposure: pilot
      data suggest an opportunity to enhance tobacco intervention.
AB  - OBJECTIVE: To assess pediatric otolaryngologists' training, actions, and
      attitudes with respect to patients exposed to secondhand smoke. STUDY DESIGN:
      Cross-sectional survey. SUBJECTS: Pediatric otolaryngologists and senior
      residents. METHODS: An anonymous, Web-based survey of pediatric otolaryngologists
      was designed to capture demographics, tobacco-specific education, actions, and
      attitudes. Responses were analyzed descriptively and entered into logistic
      regression models to determine predictors of adherence to the basic tenets of the
      general pediatrics secondhand smoke exposure-prevention guidelines. RESULTS: One
      hundred-fifteen US physicians completed the survey. Descriptive analysis revealed
      low levels of training and low levels of tobacco-specific intervention among
      respondents. Logistic regression models showed that greater tobacco-specific
      knowledge/education and fewer perceived barriers predicted greater adherence to
      the basic tenets of the pediatrics guidelines. CONCLUSION: Our pilot study
      provides preliminary evidence that can guide specific improvements in tobacco
      intervention training for pediatric otolaryngologists and residents.

PMID- 18722211
TI  - Six Sigma tympanostomy tube insertion: achieving the highest safety levels during
      residency training.
AB  - OBJECTIVE: To evaluate a protocol designed to avoid complications during
      tympanostomy tube insertion by residents. DESIGN: Ten-year consecutive cases
      series by a single surgeon supervising residents. SETTING: Tertiary children's
      hospital. PATIENTS: Children 6 weeks to 21 years. INTERVENTION: Residents
      followed a defined protocol for tube insertion. A resident operated until the
      tube was placed or he/she committed one major or two minor errors. MAIN OUTCOME
      MEASURES: Incidence of 1) major complications: profound sensorineural hearing
      loss (SNHL), injury to major vascular structures, or disruption of the ossicular
      chain; and 2) minor complications: tube loss into the middle ear, tympanic
      membrane tears, or tube occlusion by blood clot. RESULTS: There were no major
      complications in 10,000 tube insertions. Two children had unilateral profound
      SNHL; both were found to have Mondini malformations. Five tubes were recovered
      from the middle ear. Eight tympanic membrane tears healed with gelatin patches.
      Three tubes were occluded by blood clots. CONCLUSION: By following a defined
      protocol, major complications of a common operation can be reduced to the five
      sigma level and minor complications minimized.

PMID- 18722212
TI  - Cat-scratch disease of the head and neck in a pediatric population: surgical
      indications and outcomes.
AB  - OBJECTIVE: To identify the presentation of pediatric patients with head and neck
      manifestations of cat-scratch disease, one of the most common causes of subacute
      or chronic lymphadenitis in children, and to determine surgical indications and
      outcomes. STUDY DESIGN: Case series. SUBJECTS AND METHODS: All pediatric patients
      from infancy to age 19 years who presented with clinical symptoms of cat-scratch
      disease and had an IgG serological test result of more than 1:128 for Bartonella
      henselae. RESULTS: Nine patients had cat-scratch disease of the head and neck.
      Median age at presentation was 4 years; median time from symptom onset to
      presentation was 20 days. Six (67%) children underwent surgical procedures, and
      median time from presentation to surgical procedure was 43 days. CONCLUSION:
      Despite conservative treatment, a minority of pediatric patients with cat-scratch
      disease may require surgical drainage of abscess and removal of lymph nodes.
      Surgical treatment provides tissue for diagnosis, is generally well tolerated,
      affords improved recovery, and has minimal complications.

PMID- 18722213
TI  - Risks of allergy vial contamination: comparison of mixing in-office versus under
      ventilation hood.
AB  - OBJECTIVE: Compare the risk of bacterial contamination of allergy immunotherapy
      vials prepared in-office versus those mixed under a ventilation hood. STUDY
      DESIGN: Prospective single-blinded study. SETTING: Tertiary otolaryngology
      outpatient clinic. RESULTS: Five hundred thirty-seven vials were prepared and
      cultured for aerobes and anaerobes over an 11-month period. Three hundred twenty
      vials were arbitrarily assigned to in-office preparation and 217 to under-hood
      preparation. A total of two positive cultures occurred in vials prepared in
      office and one from under-hood preparation. Follow-up cultures of these three
      vials were all negative. No patients receiving injections had signs or symptoms
      of skin or systemic infections from the injections. CONCLUSION: Our results
      suggest that the risk of bacterial contamination in immunotherapy vials in both
      groups is rare.

PMID- 18722214
TI  - A comparison of the effects of botulinum toxin A and steroid injection on nasal
      allergy.
AB  - OBJECTIVES: To compare the effects of botulinum toxin A (BTX-A) with intranasal
      steroid injections on nasal symptoms in patients with allergic rhinitis (AR).
      STUDY DESIGN: A randomized, placebo-controlled, single-blinded clinical trial
      (patients were blinded). MATERIAL AND METHODS: Thirty-nine patients were included
      in the study. AR was diagnosed by means of history, clinical examination, and
      skin prick test. Patients were randomly divided into three subgroups as follows:
      in group A, 25 units of BTX-A were injected into each inferior turbinate (total
      50 units); in group B, 1 cc (20 mg/mL) of triamcinolone was injected into each
      inferior turbinate; and in group C, 1 cc of isotonic saline was injected as
      placebo. The symptoms of AR were scored by the patient on a six-point scale.
      RESULTS: At all time points, group A was significantly better than group C. In
      the nasal obstruction and rhinorrhea scores, group A was significantly better
      than group B after 8 weeks. CONCLUSION: BTX-A may provide better AR symptom
      relief in terms of duration and degree than a steroid injection.

PMID- 18722215
TI  - Interexaminer agreement of Friedman tongue positions for staging of obstructive
      sleep apnea/hypopnea syndrome.
AB  - OBJECTIVE: To determine if strong interexaminer agreement exists in identifying
      Friedman tongue positions (FTPs) for staging of obstructive sleep apnea/hypopnea
      syndrome (OSAHS). STUDY DESIGN AND METHODS: Twenty-six digital video clips of
      oropharyngeal examinations were prepared to demonstrate FTPs I through IV.
      Specific parameters for each FTP were provided to 126 examiners (otolaryngology
      residents, attendings, and fellows). The video clips were then presented to the
      examiners to determine the FTP. Kappa statistical analysis was used to evaluate
      the degree of intergrader agreement or disagreement. RESULTS: A generalized kappa
      statistic of 0.8 is considered the upper limits of substantial agreement. Thus,
      the overall kappa value (0.82) as well as all the subgroup kappa values for
      attendings (0.84), fellows (0.87), and residents (0.84) represented "very good"
      agreement. CONCLUSION: The strong interexaminer correlation of FTP demonstrated
      by this study indicates that FTP may be a useful adjunct in describing
      hypopharyngeal anatomy in patients with OSAHS.

PMID- 18722216
TI  - Evaluation of submucosal minimally invasive lingual excision technique for
      treatment of obstructive sleep apnea/hypopnea syndrome.
AB  - OBJECTIVE: Submucosal minimally invasive lingual excision (SMILE) is a novel
      approach to address hypopharyngeal obstruction. This study compares the efficacy,
      morbidity, and complications of this technique to radiofrequency reduction of the
      tongue base (RFBOT), the current standard in minimally invasive tongue base
      reduction. STUDY DESIGN: Retrospective analysis of data extracted from a
      prospective database. METHODS: Ninety-six patients who underwent SMILE (n=48) or
      RFBOT (n=48) were studied. Efficacy and safety of the procedures were compared on
      the basis of polysomnography results, morbidity measures, and complications.
      RESULTS: Patients in both groups demonstrated a significant reduction in the
      apnea/hypopnea index. Success rates for SMILE and RFBOT were 64.6 percent and
      41.7 percent, respectively (P=0.024). SMILE, however, was associated with
      increased morbidity and complications. CONCLUSION: In a comparable surgical
      protocol for obstructive sleep apnea-hypopnea syndrome, SMILE technique for
      tongue base reduction demonstrated increased efficacy over RFBOT but resulted in
      more complications. Additional experience with the procedure may reduce
      complications and increase overall efficacy.

PMID- 18722218
TI  - Evaluation of prognostic factors and middle ear risk index in tympanoplasty.
AB  - OBJECTIVE: The aim of this study was to examine the role of the prognostic
      factors and middle ear risk index on the success of tympanoplasty. STUDY DESIGN:
      Case series. SUBJECTS AND METHODS: The charts of 231 patients who underwent
      tympanoplasty operations between 2002 and 2007 were reviewed. Prognostic factors
      such as age, sex, presence of systemic diseases, location and size of
      perforation, duration of dry period, presence of myringosclerosis, presence of
      septal and conchal pathology, operation type, and status of the opposite ear and
      middle ear risk index were investigated. RESULTS: The overall success rate was
      74.4%. Multivariate analysis was carried out on significant prognostic factors to
      obtain independent variables and yielded the following results (95% CI): size of
      the perforation (<50%) (OR:8.11), healthy opposite ear (OR:5.64), more than 3
      months dry period (OR:2.21), absence of myringosclerosis (OR:4.01) and low middle
      ear risk index (OR:87.1). CONCLUSION: Size of the perforation(<50%), healthy
      opposite ear, absence of myringosclerosis, more than 3 months dry period, and low
      middle ear risk index were found to be significant independent prognostic
      factors.

PMID- 18722219
TI  - Tinnitus aurium in persons with normal hearing: 55 years later.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of silence on the
      appearance of auditory phantom perceptions in normal-hearing adults, with
      specific emphasis on the influence of suggestion. STUDY DESIGN: Cross-sectional
      survey. SUBJECTS AND METHODS: Fifty-three normal-hearing young Caucasian adults
      were subjected to two 4-minute sessions in an anechoic sound chamber. In the
      first session the chamber was empty; in the second session the chamber contained
      a nonfunctioning loudspeaker. At the end of each session, subjects had to
      indicate which sounds they perceived from a list of 23 different sounds. RESULTS:
      When the loudspeaker was not present, 83 percent of the participants reported
      that they experienced at least one sound, and the percentage increased to 92
      percent when the loudspeaker was present. CONCLUSION: These results confirm the
      emergence of tinnituslike perceptions in a nonclinical population in a silent
      environment and indicate that suggestive mechanisms play only a minor role in
      their generation.

PMID- 18722220
TI  - The changes of MRSA infections in chronic suppurative otitis media.
AB  - OBJECTIVES: To investigate the epidemiologic and microbiological characteristics
      of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and
      hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA)
      infections in the otorrhea of chronic suppurative otitis media (COM) patients.
      DESIGN: Retrospective study of patients with newly identified MRSA infections
      from January 1998 through December 2006. A total of 2773 patients with a
      diagnosis of COM were included in this study. An antibiotic sensitivity test was
      performed for each isolate. RESULTS: The prevalence of MRSA in COM was 4.9
      percent (137 of 2773 patients). The proportion of CA-MRSA rose from 0.7 percent
      in 1998 to 11.4 percent in 2006. However, the proportion of HA-MRSA did not
      change significantly, from 0.7 percent in 1999 to 1.3 percent in 2006. All of the
      CA-MRSA strains identified in our study were susceptible to
      trimethoprim/sulfamethoxazole (TMP/SMX). Rifampin susceptibility was also noted
      in 90 percent of the cases. CONCLUSIONS: CA-MRSA infections have risen
      dramatically in the past decade. CA-MRSA and HA-MRSA in COM differed in both
      clinical and microbiological aspects.

PMID- 18722221
TI  - Residual hearing preservation after cochlear implantation: comparison between
      straight and perimodiolar implants.
AB  - OBJECTIVE: Investigate whether perimodiolar cochlear implants provide a better
      preservation of residual hearing than straight implants. STUDY DESIGN AND
      SETTING: Longitudinal, observational, and comparative study in tertiary center in
      Mexico City. Forty-eight patients who underwent cochlear implant surgery were
      included and were divided into two groups depending on whether they received a
      straight or a perimodiolar implant. The residual hearing of the operated ear was
      measured audiometrically before and after surgery. Variables analyzed were pure
      tone average threshold at 125, 250, and 500 Hz and residual hearing at
      frequencies from 125 to 8000 Hz. Residual hearing was considered as preserved
      when audiometric changes were less than 10 dB HL in each variable. RESULTS: No
      statistically significant difference was found in the preservation of residual
      hearing between the two groups or between individual devices (P>0.05 in all
      variables). CONCLUSION: Straight and perimodiolar cochlear implants seem to
      preserve residual hearing at similar rates across frequencies.

PMID- 18722222
TI  - Clinical experience with symptomatic superior canal dehiscence in a single
      neurotologic practice.
AB  - OBJECTIVE: To discuss the range of signs and symptoms of patients with superior
      canal dehiscence syndrome identified in a single neurotologic practice. STUDY
      DESIGN: Retrospective chart review of 35 patients diagnosed with superior canal
      dehiscence from April 2000 to June 2007. RESULTS: All patients had evidence of
      superior canal dehiscence on computed tomography. These 35 patients represented
      0.56% of new patients seen over a five-year period. The incidence of clinical
      symptoms and signs is compared to other published series. The mean vestibular
      evoked myogenic potential thresholds of affected ears are significantly lower
      than the mean vestibular evoked myogenic potential thresholds of unaffected ears.
      To date, 5 of 35 patients have undergone transmastoid occlusion of the superior
      semicircular canal with significant improvement in clinical symptoms in 4 of 5
      cases. CONCLUSION: Not all patients with a diagnosis of superior canal dehiscence
      syndrome will have classic symptoms and signs. A high index of suspicion with
      careful clinical examination and properly performed ancillary testing is required
      to confirm this diagnosis.

PMID- 18722223
TI  - Double-blind, placebo-controlled trial with esomeprazole for symptoms and signs
      associated with laryngopharyngeal reflux.
AB  - OBJECTIVE: To determine the efficacy of proton pump inhibitor (PPI) therapy with
      esomeprazole on symptoms and signs associated with laryngopharyngeal reflux
      (LPR). STUDY DESIGN AND METHODS: Prospective, double-blind, randomized, placebo
      controlled study. Sixty-two patients with a reflux finding score (RFS)>7 and a
      reflux symptom index (RSI)>13 were enrolled and received either esomeprazole 20
      mg twice daily or placebo for three months. RSI and RFS were assessed at
      baseline, after six weeks, and after three months. RESULTS: Reductions of total
      RSI and RFS as well as of several subscores were significantly higher in the
      treatment group compared to placebo after three months (P<0.05 each). The
      difference between study groups was most pronounced for posterior commissure
      hypertrophy (P<0.01). CONCLUSION: In the treatment of LPR-related symptoms a high
      placebo effect can be observed. However, compared to control, twice-daily PPI
      treatment for three months demonstrated a significantly greater improvement in
      laryngeal appearance and LPR symptoms.

PMID- 18722225
TI  - Pharyngeal adaptation in Zenker's diverticulum: the "faux pharyngoesophageal
      segment".
AB  - BACKGROUND: We have noticed a protrusion on the pharyngeal wall in patients with
      Zenker's diverticulum (ZD). The protrusion gives the appearance of a neo
      pharyngoesophageal segment (faux-PES) and may represent an adaptation to protect
      the airway. STUDY DESIGN: A case-control study. METHODOLOGY: The fluoroscopic
      swallow studies of patients with ZD were compared with matched controls.
      Information regarding the presence and location of a faux-PES, true PES opening,
      pharyngeal constriction, and laryngohyoid elevation was compared. RESULTS: The
      fluoroscopic swallow studies of 31 patients with ZD were compared with 31
      controls. A faux-PES was found in 100 percent of ZD patients and in 0 percent of
      controls. The mean maximum opening of the faux-PES was 1.5 (+/-0.27) cm. The faux
      PES was located 1 cm above the true PES below the entrance to the supraglottic
      airway. This is the optimal location for airway defense. CONCLUSIONS: The faux
      PES was identified in 100 percent of patients with ZD. The faux-PES may represent
      a physiologic adaptation to protect the airway from regurgitation out of a ZD.

PMID- 18722224
TI  - Vocal outcome measures after bilateral posterior cricoarytenoid muscle botulinum
      toxin injections for abductor spasmodic dysphonia.
AB  - OBJECTIVE: To review vocal outcome measures, using the Voice Related Quality of
      Life (VRQOL) index, after simultaneous bilateral posterior cricoarytenoid muscle
      botulinum toxin injections. STUDY DESIGN: Case series. SETTING: Tertiary care
      academic clinic. SUBJECTS AND METHODS: Fourteen subjects with abductor spasmodic
      dysphonia received 37 simultaneous bilateral posterior cricoarytenoid muscle
      botulinum toxin injections for isolated abductor spasmodic dysphonia (ABSD) over
      a 16-month period. MAIN OUTCOME MEASURES: VRQOL index. RESULTS: Of the 37
      injections, 33 of 37 (89%) resulted in improvement. Three injections resulted in
      no improvement, and one injection resulted in a worse VRQOL. The overall VRQOL
      mean improvement was 19.8 (range 5-53), with an average pre/postinjection VRQOL
      interval of 36 days (range 21-45 days). CONCLUSIONS: Simultaneous bilateral
      posterior cricoarytenoid muscle botulinum injections result in a statistically
      significant improvement in VRQOL index scores for a high percentage of ABSD
      patients, thus improving patient quality of life.

PMID- 18722227
TI  - Clinical significance of micrometastases detection in lymph nodes from head and
      neck squamous cell carcinoma.
AB  - OBJECTIVE: Study the clinical relevance of micrometastases in head and neck
      squamous cell carcinoma (HNSCC). METHODS: We reviewed the outcome of 31 patients
      who underwent neck dissection for HNSCC with lymph node analysis by cytokeratin
      19 real-time Taqman polymerase chain reaction (CK19RT-PCR) for detection of
      micrometastasis. Fifteen patients were N+ on histopathology (group 1) and 16 were
      N-; nine of these 16 patients were CK19RT-PCR positive (group 2), whereas seven
      were negative (group 3). Local and neck recurrences, metastases, and other tumour
      sites were recorded during follow-up. RESULTS: Five patients in group 1, eight
      patients in group 2, and one patient in group 3 experienced a tumor-related
      event. N- patients in groups 2 and 3 had a different outcome (P<0.01).
      CONCLUSION: It is suggested that CK19RTPCR detection of micrometastasis in lymph
      nodes could be of significant prognostic value in HNSCC, because more aggressive
      treatment could be indicated in these patients.

PMID- 18722226
TI  - Prognostic factors of unknown primary head and neck squamous cell carcinoma.
AB  - OBJECTIVE: To evaluate the prognostic factors of unknown primary head and neck
      squamous cell carcinoma (HNSCC). STUDY DESIGN: Retrospective study. SUBJECTS:
      Patients with unknown primary HNSCC from 1980 to 2000 were included. RESULTS:
      Forty-eight patients, predominantly male and with a mean age of 63.3+/-11.6
      years, were recruited. The median survival time (MST) was 44 months. The overall
      survival rate was 60.4 percent at three years and 39.6 percent at five years.
      Forty-two patients receiving intervention regimens had a MST of 45 months, while
      six patients receiving palliative therapy had a MST of 8.5 months (log rank test,
      P=0.016). With multivariate Cox regression analysis, age (per year), higher nodal
      stage (N3 vs N1 or N2), and treatment (operation vs nonoperation) had a hazard
      ratio of 1.081 (P<0.0001), 5.852 (P=0.010), and 0.4 (P=0.042), respectively.
      CONCLUSION: Older age, higher nodal stage, and palliative treatment indicated
      poor prognosis. Survival time might be prolonged if surgical treatment is
      tolerable.

PMID- 18722228
TI  - The administration of IL-12/GM-CSF and Ig-4-1BB ligand markedly decreases murine
      floor of mouth squamous cell cancer.
AB  - OBJECTIVE: To assess immune-based gene therapy in a murine floor of mouth (FOM)
      squamous cell carcinoma (SCC) model. STUDY DESIGN: In vitro and in vivo testing
      of immune therapy for SCC. METHODS: Multiple SCC lines were infected by using
      advRSV-interleukin-12 (IL-12) and advCMV-interleukin-12/granulocyte macrophage
      colony-stimulating factor (IL-12/GM-CSF) and monitored for production of IL-12
      and GM-CSF. Intratumoral injections of viral vectors were administered with
      systemic Ig-4-1BB ligand in an orthotopic murine FOM SCC model and followed for
      tumor size and survival. RESULTS: In vitro, all cell lines produced substantial
      levels of IL-12 and GM-CSF. In vivo, tumors treated with advCMV-IL-12/GM-CSF and
      Ig-4-1BBL showed a striking reduction in tumor volume (vs control P<0.0001) and
      improved median survival (38 days vs 19 days for control, P<0.0001). CONCLUSION:
      Combination immune-based therapies effectively improve survival in mice bearing
      FOM SCC over single-modality therapy.

PMID- 18722229
TI  - Use of computerized manometry for the detection of pharyngoesophageal spasm in
      tracheoesophageal speech.
AB  - OBJECTIVE: To evaluate the utility of computerized manometry (CM) to identify
      pharyngoesophageal segment (PES) spasm during tracheoesophageal speech. STUDY
      DESIGN: Prospective clinical, controlled study. SUBJECTS AND METHODS:
      Intraluminal pressures of the PES were collected in 12 tracheoesophageal speakers
      without spasm and 8 tracheoesophageal speakers with PES spasm before and after
      localized injection of botulinum toxin to the PES. All subjects underwent voice
      analysis and videofluoroscopy in addition to CM before and after treatment.
      RESULTS: All tracheoesophageal speakers with PES spasm presented with mean
      intraluminal pressures greater than 16 mmHg (mean, 25.36 mmHg). In contrast, mean
      intraluminal pressures of subjects without spasm was 11.76 mmHg (P<0.05). The
      negative predictive value associated with the use of 16 mmHg as a threshold value
      for spasm was 100%. CONCLUSION: CM is a clinically useful tool to aid in speech
      rehabilitation for tracheoesophageal speakers. Intraluminal pressures of greater
      than 16 mmHg was highly predictive for PES spasm.

PMID- 18722230
TI  - Postoperative bleeding in transoral laser microsurgery for upper aerodigestive
      tract tumors.
AB  - OBJECTIVES: To report the incidence, cause, and outcome of bleeding after
      transoral laser microsurgery. STUDY DESIGN: A two-center prospective case series
      analysis. SUBJECTS AND METHODS: Seven hundred one patients underwent transoral
      laser microsurgery for tumors of the oral cavity, pharynx, and larynx from June
      1996 through September 2006. RESULTS: Ten patients (1.4%) experienced
      postoperative bleeding between 0 and 17 days after surgery. Five patients had
      previously untreated tumors, and five patients had salvage surgery. Two patients
      (0.3%) had minor bleeding and required observation only. Five patients (0.7%)
      experienced major bleeding requiring exploration under general anesthesia. Three
      patients (0.4%) had catastrophic life-threatening bleeds, two of whom died. The
      bleeding vessel was identified as the lingual artery in four patients, the
      superior laryngeal artery in two, the facial artery in two, and unknown in two.
      CONCLUSIONS: Bleeding after transoral laser microsurgery is rare but potentially
      life-threatening.

PMID- 18722231
TI  - Actinomycosis of the paranasal sinus.
AB  - OBJECTIVE: To report clinical characteristics and treatment outcomes of
      actinomycosis of the paranasal sinus. STUDY DESIGN: Retrospective review.
      SUBJECTS AND METHODS: The medical records of six patients with actinomycosis of
      the paranasal sinus between 1998 and 2006 were analyzed. RESULTS: There were no
      immunocompromised patients and all lesions were unilateral. Only one patient had
      a history of an oroantral fistula due to facial trauma. On CT scan, all patients
      had unilateral opacification of the maxillary sinus with focal calcified
      densities. All cases underwent endoscopic sinus surgery followed by relatively
      short-term antibiotic administration, and there was no recurrence. CONCLUSIONS:
      Chronic unilateral maxillary sinusitis, a calcified density in the involved sinus
      on radiological studies, and unresponsiveness to antibiotics are characteristics
      of actinomycotic sinusitis. Surgical removal of the involved tissues and the
      restoration of sinus ventilation seem to be important factors for treating the
      disease.

PMID- 18722232
TI  - Pharyngolaryngeal sarcoidosis: report of 12 cases.

PMID- 18722233
TI  - Methylene blue for easy and safe detection of salivary duct papilla in
      sialendoscopy.

PMID- 18722234
TI  - An exophytic localized lymphoma of the tongue base.

PMID- 18722235
TI  - Infantile facial nerve course in an adult patient with congenital aural
      dysplasia.

PMID- 18722236
TI  - Intestinal-type ethmoid adenocarcinoma in sinonasal polyposis.

PMID- 18722237
TI  - Primary laryngeal manifestation in precursor T-cell acute lymphoblastic leukemia.

PMID- 18722238
TI  - Acute bilateral facial palsy and Wegener's disease.

PMID- 18722239
TI  - External auditory canal meningoencephalocele with spontaneous cerebrospinal
      otorrhea.

PMID- 18722240
TI  - Recurrent petrous apex cholesteatoma in a patient with basal cell nevus syndrome.

PMID- 18722241
TI  - External auditory exostoses: evaluation and treatment.

PMID- 18722243
TI  - Images in emergency medicine. Intussusception.

PMID- 18722245
TI  - Images in emergency medicine. Low-flow (ischemic) priapism.

PMID- 18722246
TI  - Images in emergency medicine. Luxatio erecta (inferior shoulder dislocation).

PMID- 18722247
TI  - Smoke and shadows: measuring hospital disaster preparedness.

PMID- 18722248
TI  - Annals of Emergency Medicine Journal Club. Out-of-hospital continuous positive
      airway pressure ventilation versus usual care in acute respiratory failure: a
      randomized controlled trial.
AB  - WHAT IS ALREADY KNOWN ON THIS TOPIC: Application of continuous positive airway
      pressure (CPAP) for patients with acute respiratory distress reduces the need for
      tracheal intubation and mechanical ventilation. Case series have demonstrated
      CPAP's feasibility in out-of-hospital settings. WHAT QUESTION THIS STUDY
      ADDRESSED: Seventy-one out-of-hospital patients with severe respiratory distress,
      randomized to receive CPAP or usual care, were assessed to determine need for
      tracheal intubation and mortality. WHAT THIS STUDY ADDS TO OUR KNOWLEDGE: Within
      the CPAP group, the rate of intubation was 30% less than the usual care group,
      and mortality was 20% lower. HOW THIS MIGHT CHANGE CLINICAL PRACTICE: Emergency
      medical services systems and their medical directors should consider making CPAP
      available as part of the treatment for out-of-hospital severe respiratory
      distress patients, particularly in systems with long transport times.

PMID- 18722249
TI  - Update on emerging infections: news from the Centers for Disease Control and
      Prevention. Emergence of fluoroquinolone-resistant Neisseria meningitidis-
      Minnesota and North Dakota, 2007-2008.

PMID- 18722250
TI  - Balad's green doors.

PMID- 18722251
TI  - Images in emergency medicine. Pneumothorax.

PMID- 18722252
TI  - Images in emergency medicine. Intussusception.

PMID- 18722253
TI  - Magnetic resonance-induced thermal burn.

PMID- 18722254
TI  - Presence of family members during resuscitation.

PMID- 18722255
TI  - What do recent studies on lumpectomy cavity volume change imply for breast
      clinical target volumes?

PMID- 18722256
TI  - Understanding the risk of second malignant tumors in children with Hodgkin's
      disease.

PMID- 18722257
TI  - Pain and suffering during cancer therapy: continued sins of omission.

PMID- 18722258
TI  - A call to action: hospice and palliative medicine board certification.

PMID- 18722259
TI  - Hypofractionation, long-term effects, and the alpha/beta ratio.

PMID- 18722260
TI  - Assessment of technological advances in radiation oncology: from whence comes the
      funding?

PMID- 18722261
TI  - Balancing on a knife's edge: evidence-based medicine and the marketing of health
      technology.

PMID- 18722263
TI  - Subsequent malignancies in children treated for Hodgkin's disease: associations
      with gender and radiation dose.
AB  - PURPOSE: Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity
      and mortality in children treated for Hodgkin's disease (HD). We evaluated select
      demographic and therapeutic factors associated with SMNs, specifically gender and
      radiation dose. METHODS AND MATERIALS: A total of 930 children treated for HD at
      five institutions between 1960 and 1990 were studied. Mean age at diagnosis was
      13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment
      included radiation alone (43%), chemotherapy alone (9%), or both (48%). RESULTS:
      We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate
      of 19%. With 15,154 patient years of follow-up, only 7.18 cancers were expected
      (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63
      cases/10,000 years). The SIR for female subjects, 19.93, was significantly
      greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR
      for female patients was 15.4, still significantly greater than for male patients
      (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p
      = 0.0085). On univariate analysis, an increased risk was associated with female
      gender, increasing radiation dose, and age at treatment (12-16 years). Using
      logistic regression, mantle radiation dose increased risk, and this was 2.5-fold
      for female patients treated with more than 35 Gy primarily because of breast
      cancer. CONCLUSIONS: Survivors of childhood HD are at risk for SMNs, and this
      risk is greater for female individuals even after accounting for breast cancer.
      Although SMNs occur in the absence of radiation therapy, the risk increases with
      RT dose.

PMID- 18722264
TI  - Unilateral and bilateral breast cancer in women surviving pediatric Hodgkin's
      disease.
AB  - PURPOSE: To define demographic and therapeutic associations with the risk of
      breast cancer in children treated for Hodgkin's disease (HD), particularly the
      frequency and interval to the development of contralateral breast cancer. METHODS
      AND MATERIALS: All 398 female patients (<19 years) treated for HD in five
      institutions during the accrual period were evaluated. Mean follow-up was 16.9
      years. The standardized incidence ratio (SIR) was calculated as the ratio of the
      observed number of cases to the expected number of cases, estimated using age
      matched controls from the Surveillance, Epidemiology, and End Results database.
      RESULTS: A total of 29 women developed breast cancer (25 invasive, 4 ductal
      carcinoma in situ; SIR, 37.25; 95% confidence interval, 24.96-53.64). Time to
      diagnosis was 9.4 to 36.1 years. Cumulative incidence was 24% at 30 years. Ten
      patients (34%) had bilateral disease (9 metachronous, 1 synchronous). The
      interval to contralateral breast cancer was 12 to 34 months. On univariate
      analysis, significant variables included stage of HD, mantle radiation dose,
      pelvic radiation (protective), and follow-up time. On multivariate analysis,
      early stage and older age at diagnosis of HD (<or=12 vs. >12 years) were
      significant predictors of secondary breast cancer. CONCLUSIONS: Women surviving
      pediatric HD were found to have a 37-fold increase in the risk of breast cancer
      and a high likelihood of rapidly developing bilateral disease. Early-stage HD and
      age greater than 12 years at diagnosis of HD were independent risk factors.
      Higher radiation doses may augment risk, and pelvic radiation may be protective.
      Breast cancer screening methodology and frequency, plus the role of prophylaxis
      in patients with unilateral disease, require definition.

PMID- 18722265
TI  - Phase I study of preoperative radiation therapy with concurrent infusional 5
      fluorouracil and oxaliplatin followed by surgery and postoperative 5-fluorouracil
      plus leucovorin for T3/T4 rectal adenocarcinoma: ECOG E1297.
AB  - PURPOSE: Oxaliplatin is a platinum analog and radiosensitizer active in
      colorectal cancer. We performed a Phase I trial to test the safety and
      preliminary efficacy of adding oxaliplatin to standard preoperative
      chemoradiation therapy for rectal cancer. METHODS AND MATERIALS: Eligible
      patients had T3 to T4 rectal adenocarcinoma. Patients received standard-dose
      radiation (50.4 Gy for 5.5 weeks) with concurrent infused 5-fluorouracil (5-FU)
      at 200 mg/m2 per day, 7 days per week. Oxaliplatin was given three times at 14
      day intervals at 55, 70, or 85 mg/m2 during the 5.5-week radiation period, before
      resection. Adjuvant therapy consisted of four cycles of 5-FU (500 mg/m2 per week)
      with leucovorin (500 mg/m2 per week) given every 6 weeks. The main goals were to
      identify the maximum tolerated dose of oxaliplatin and the dose-limiting
      toxicities when given with 5-FU and RT. Secondary goals were to determine
      resectability, pathologic response, sphincter preservation, and overall survival
      rates. RESULTS: Twenty-one patients were enrolled, 5 at the 55 mg/m2 oxaliplatin
      dose level, 5 at 70 mg/m2, and 11 at 85 mg/m2. All patients were able to complete
      the preoperative chemoradiation regimen with no dose adjustments. No dose
      limiting toxicities or differences in the type or extent of toxicity were noted
      among the groups. Nineteen patients underwent surgery (three abdominopelvic
      resections and 16 low anterior resections), for an 84% sphincter preservation
      rate. The pathologic complete response rate was 26% (5 patients), and minimal
      microscopic residual tumor was found in 21% (4 additional patients). CONCLUSIONS:
      Oxaliplatin was well tolerated at 85 mg/m2 given every 2 weeks in combination
      with standard preoperative chemoradiation for rectal cancer. The rates of major
      pathologic response and sphincter preservation are promising.

PMID- 18722266
TI  - Loss of Raf kinase inhibitory protein induces radioresistance in prostate cancer.
AB  - PURPOSE: External beam radiotherapy (RT) is often used in an attempt to cure
      localized prostate cancer (PCa), but it is only palliative against disseminated
      disease. Raf kinase inhibitory protein (RKIP) is a metastasis suppressor whose
      expression is reduced in approximately 50% of localized PCa tissues and is absent
      in metastases. Chemotherapeutic agents have been shown to induce tumor apoptosis
      through induction of RKIP expression. Our goal was to test whether RT similarly
      induces apoptosis through induction of RKIP expression. METHODS AND MATERIALS:
      The C4-2B PCa cell line was engineered to overexpress or underexpress RKIP. The
      engineered cells were tested for apoptosis in cell culture and tumor regression
      in mice after RT. RESULTS: RT induced both RKIP expression and apoptosis of PCa
      cells. Overexpression of RKIP sensitized PCa cells to radiation-induced
      apoptosis. In contrast, short-hairpin targeting of RKIP, so that RT could not
      induce RKIP expression, protected cells from radiation-induced apoptosis. In a
      murine model, knockdown of RKIP in PCa cells diminished radiation-induced
      apoptosis. Molecular concept mapping of genes altered on manipulation of RKIP
      expression revealed an inverse correlation with the concept of genes altered by
      RT. CONCLUSION: The data presented in this report indicate that the loss of RKIP,
      as seen in primary PCa tumors and metastases, confers protection against
      radiation-induced apoptosis. Therefore, it is conceivable that the loss of RKIP
      confers a growth advantage on PCa cells at distant sites, because the loss of
      RKIP would decrease apoptosis, favoring proliferation.

PMID- 18722267
TI  - Overexpression of intrinsic hypoxia markers HIF1alpha and CA-IX predict for local
      recurrence in stage T1-T2 glottic laryngeal carcinoma treated with radiotherapy.
AB  - PURPOSE: To examine the prognostic value of three endogenous hypoxia markers
      (hypoxia inducible factor 1 alpha subunit [HIF1 alpha], carbonic anhydrase IX [CA
      IX], and glucose transporter type 1 [GLUT-1]) on the clinical outcome in patients
      with early-stage glottic carcinoma primarily treated with radiotherapy (RT) and
      to determine the predictive hypoxic profile to choose the optimal treatment of
      early-stage laryngeal carcinoma. METHODS AND MATERIALS: Immunohistochemistry for
      HIF1 alpha, CA-IX, and GLUT-1 was performed on formalin-fixed, paraffin-embedded,
      pretreatment tissue samples of 91 glottic squamous cell carcinoma specimens. The
      patient group consisted only of those with early-stage (T1-T2) glottic carcinoma,
      and all patients were treated with RT only. Relative tumor staining was scored on
      the tissue samples. Receiver operating curve analysis was performed to determine
      the optimal cutoff value for each tumor marker. Cox regression analyses for the
      variables HIF1 alpha, CA-IX, GLUT-1, gender, age, hemoglobin level, T category, N
      category, tobacco use, and alcohol use were performed with local control and
      overall survival as endpoints. RESULTS: HIF1 alpha overexpression in early-stage
      glottic carcinoma correlated significantly with worse local control (hazard ratio
      [HR], 3.05; p = 0.021) and overall survival (HR, 2.92; p = 0.016). CA-IX
      overexpression correlated significantly with worse local control (HR, 2.93; p =
      0.020). GLUT-1 overexpression did not show any correlation with the clinical
      outcome parameters. Tumors with a nonhypoxic profile (defined as low HIF1 alpha
      and low CA-IX expression) had significantly better local control (HR, 6.32; p =
      0.013). CONCLUSION: The results of our study have shown that early-stage glottic
      laryngeal carcinomas with low HIF1 alpha and CA-IX expression are highly curable
      with RT. For this group, RT is a good treatment option. For tumors with HIF1
      alpha or CA-IX overexpression, hypoxic modification before RT or primary surgical
      treatment should be considered.

PMID- 18722268
TI  - Increased but error-prone nonhomologous end joining in immortalized
      lymphoblastoid cell extracts from adult cancer patients with late radionecrosis.
AB  - PURPOSE: To study nonhomologous end joining in extracts of two lymphoblastoid
      cell lines derived from patients with late radionecrosis after radiotherapy. Both
      cell lines were previously shown to exhibit impaired rejoining of DNA double
      strand breaks in a pulse-field gel electrophoresis assay. METHODS AND MATERIALS:
      We used a cell-free system and quantitative real-time polymerase chain reaction,
      as well as sequencing analysis of end joining products. RESULTS: Paradoxically,
      extracts of the two cell lines display increased rates of in vitro end joining of
      noncohesive termini compared with normal cell extracts. This increase was seen in
      the absence of added deoxyribonucleoside triphosphates and was sensitive to
      inhibition by wortmannin. Sequencing of the joined products revealed that,
      despite increased rates of end joining, the process was error prone with a
      greater frequency of deletions compared with that observed in normal controls.
      CONCLUSION: These findings are consistent with the suggestion that a promiscuous,
      deletion-prone abnormality of nonhomologous end joining might underpin the
      predisposition of certain radiotherapy patients to late radionecrosis. We
      hypothesize that some individuals might harbor subclinical defects in
      nonhomologous end joining that clinically manifest on challenge with high-dose
      radiation. Because both quantitative and qualitative aspects of end joining have
      demonstrably been influenced, we recommend that the study of patient samples
      should involve a combination of quantitative methods (e.g., quantitative real
      time polymerase chain reaction), sequencing analysis, and a comparison of
      multiple join types.

PMID- 18722269
TI  - Relative biologic effects of low-dose-rate alpha-emitting 227Th-rituximab and
      beta-emitting 90Y-tiuexetan-ibritumomab versus external beam X-radiation.
AB  - PURPOSE: To determine the relative biologic effects (RBE) of alpha-particle
      radiation from 227Th-rituximab and of beta-radiation from 90Y-tiuexetan
      ibritumomab (Zevalin) compared with external beam X-radiation in the Raji
      lymphoma xenograft model. METHODS AND MATERIALS: Radioimmunoconjugates were
      administered intravenously in nude mice with Raji lymphoma xenografts at
      different levels of activity. Absorbed dose to tumor was estimated by separate
      biodistribution experiments for 227Th-rituximab and Zevalin. Tumor growth was
      measured two to three times per week after injection or X-radiation. Treatment
      induced increase in growth delay to reach tumor volumes of 500 and 1,000 mm3,
      respectively, was used as an end point. RESULTS: The absorbed radiation dose-rate
      in tumor was slightly more than 0.1 Gy/d for the first week following injection
      of 227Th-rituximab, and thereafter gradually decreased to 0.03 Gy/d at 21 days
      after injection. For treatment with Zevalin the maximum dose-rate in tumor was
      achieved already 6 h after injection (0.2 Gy/d), and thereafter decreased to 0.01
      Gy/d after 7 days. The relative biologic effect was between 2.5 and 7.2 for 227Th
      rituximab and between 1 and 1.3 for Zevalin. CONCLUSIONS: Both at low doses and
      low-dose-rates, the 227Th-rituximab treatment was more effective per absorbed
      radiation dose unit than the two other treatments. The considerable effect at low
      doses suggests that the best way to administer low-dose-rates, alpha-emitting
      radioimmunoconjugates is via multiple injections.

PMID- 18722271
TI  - Improving soft-tissue contrast in four-dimensional computed tomography images of
      liver cancer patients using a deformable image registration method.
AB  - PURPOSE: To investigate a deformable image registration method to improve soft
      tissue contrast in four-dimensional (4D) computed tomography (CT) images of the
      liver. METHODS AND MATERIALS: Ten patients with hepatocellular carcinoma
      underwent 4D CT scan for radiotherapy treatment planning on a positron emission
      tomography/CT scanner. Four-dimensional CT images were binned into 10 equispaced
      phases. The exhale phase served as the reference phase, and images from the other
      nine phases were coregistered to the reference phase image using an intensity
      based, automatic deformable image registration method. Then the coregistered
      images were combined to create a single, high-quality reconstructed CT image at
      exhale phase as the new reference for target delineation. The extent of image
      quality enhancement was quantified relative to the original CT by calculating the
      signal-to-noise ratio and the contrast-to-noise ratio. RESULTS: The soft tissue
      image contrast was noticeably better after deformable image registration than in
      the original scans. Signal-to-noise ratios inside the liver region of interest
      increased for all patients by a factor of 3.0 (range, 2.3-3.7). The improvement
      in image quality was not linearly proportionate to the number of images averaged.
      Using only 6 phases can achieve at least 85% of the contrast enhancement that can
      be achieved using all 10 phases. We also found that contrast enhancement was
      inversely proportional to the original image quality (p = 0.006), and the
      contrast enhancement is attained with little loss of spatial resolution.
      CONCLUSIONS: This deformable image registration method is feasible to improve
      soft-tissue image quality in 4D CT images.

PMID- 18722270
TI  - Engineered modular recombinant transporters: application of new platform for
      targeted radiotherapeutic agents to alpha-particle emitting 211 At.
AB  - PURPOSE: To generate and evaluate a modular recombinant transporter (MRT) for
      targeting 211 At to cancer cells overexpressing the epidermal growth factor
      receptor (EGFR). METHODS AND MATERIALS: The MRT was produced with four functional
      modules: (1) human epidermal growth factor as the internalizable ligand, (2) the
      optimized nuclear localization sequence of simian vacuolating virus 40 (SV40)
      large T-antigen, (3) a translocation domain of diphtheria toxin as an
      endosomolytic module, and (4) the Escherichia coli hemoglobin-like protein (HMP)
      as a carrier module. MRT was labeled using N-succinimidyl 3-[211 At]astato-5
      guanidinomethylbenzoate (SAGMB), its 125 I analogue SGMIB, or with 131 I using
      Iodogen. Binding, internalization, and clonogenic assays were performed with EGFR
      expressing A431, D247 MG, and U87MG.wtEGFR human cancer cell lines. RESULTS: The
      affinity of SGMIB-MRT binding to A431 cells, determined by Scatchard analysis,
      was 22 nM, comparable to that measured before labeling. The binding of SGMIB-MRT
      and its internalization by A431 cancer cells was 96% and 99% EGFR specific,
      respectively. Paired label assays demonstrated that compared with Iodogen-labeled
      MRT, SGMIB-MRT and SAGMB-MRT exhibited more than threefold greater peak levels
      and durations of intracellular retention of activity. SAGMB-MRT was 10-20 times
      more cytotoxic than [211 At]astatide for all three cell lines. CONCLUSION: The
      results of this study have demonstrated the initial proof of principle for the
      MRT approach for designing targeted alpha-particle emitting radiotherapeutic
      agents. The high cytotoxicity of SAGMB-MRT for cancer cells overexpressing EGFR
      suggests that this 211 At-labeled conjugate has promise for the treatment of
      malignancies, such as glioma, which overexpress this receptor.

PMID- 18722272
TI  - Performance evaluation of automatic anatomy segmentation algorithm on repeat or
      four-dimensional computed tomography images using deformable image registration
      method.
AB  - PURPOSE: Auto-propagation of anatomic regions of interest from the planning
      computed tomography (CT) scan to the daily CT is an essential step in image
      guided adaptive radiotherapy. The goal of this study was to quantitatively
      evaluate the performance of the algorithm in typical clinical applications.
      METHODS AND MATERIALS: We had previously adopted an image intensity-based
      deformable registration algorithm to find the correspondence between two images.
      In the present study, the regions of interest delineated on the planning CT image
      were mapped onto daily CT or four-dimensional CT images using the same
      transformation. Postprocessing methods, such as boundary smoothing and
      modification, were used to enhance the robustness of the algorithm. Auto
      propagated contours for 8 head-and-neck cancer patients with a total of 100
      repeat CT scans, 1 prostate patient with 24 repeat CT scans, and 9 lung cancer
      patients with a total of 90 four-dimensional CT images were evaluated against
      physician-drawn contours and physician-modified deformed contours using the
      volume overlap index and mean absolute surface-to-surface distance. RESULTS: The
      deformed contours were reasonably well matched with the daily anatomy on the
      repeat CT images. The volume overlap index and mean absolute surface-to-surface
      distance was 83% and 1.3 mm, respectively, compared with the independently drawn
      contours. Better agreement (>97% and <0.4 mm) was achieved if the physician was
      only asked to correct the deformed contours. The algorithm was also robust in the
      presence of random noise in the image. CONCLUSION: The deformable algorithm might
      be an effective method to propagate the planning regions of interest to
      subsequent CT images of changed anatomy, although a final review by physicians is
      highly recommended.

PMID- 18722273
TI  - Feasibility of a multigroup deterministic solution method for three-dimensional
      radiotherapy dose calculations.
AB  - PURPOSE: To investigate the potential of a novel deterministic solver, Attila,
      for external photon beam radiotherapy dose calculations. METHODS AND MATERIALS:
      Two hypothetical cases for prostate and head-and-neck cancer photon beam
      treatment plans were calculated using Attila and EGSnrc Monte Carlo simulations.
      Open beams were modeled as isotropic photon point sources collimated to specified
      field sizes. The sources had a realistic energy spectrum calculated by Monte
      Carlo for a Varian Clinac 2100 operated in a 6-MV photon mode. The Attila
      computational grids consisted of 106,000 elements, or 424,000 spatial degrees of
      freedom, for the prostate case, and 123,000 tetrahedral elements, or 492,000
      spatial degrees of freedom, for the head-and-neck cases. RESULTS: For both cases,
      results demonstrate excellent agreement between Attila and EGSnrc in all areas,
      including the build-up regions, near heterogeneities, and at the beam penumbra.
      Dose agreement for 99% of the voxels was within the 3% (relative point-wise
      difference) or 3-mm distance-to-agreement criterion. Localized differences
      between the Attila and EGSnrc results were observed at bone and soft-tissue
      interfaces and are attributable to the effect of voxel material homogenization in
      calculating dose-to-medium in EGSnrc. For both cases, Attila calculation times
      were <20 central processing unit minutes on a single 2.2-GHz AMD Opteron
      processor. CONCLUSIONS: The methods in Attila have the potential to be the basis
      for an efficient dose engine for patient-specific treatment planning, providing
      accuracy similar to that obtained by Monte Carlo.

PMID- 18722275
TI  - Comparison of dosimetric and biologic effective dose parameters for prostate and
      urethra using 131 Cs and 125 I for prostate permanent implant brachytherapy.
AB  - PURPOSE: To compare the urethral and prostate absolute and biologic effective
      doses (BEDs) for 131 Cs and 125 I prostate permanent implant brachytherapy (PPI).
      METHODS AND MATERIALS: Eight previously implanted manually planned 125 I PPI
      patients were replanned manually with 131 Cs, and re-planned using Inverse
      Planning Simulated Annealing. 131 Cs activity and the prescribed dose (115 Gy)
      were determined from that recommended by IsoRay. The BED was calculated for the
      prostate and urethra using an alpha/beta ratio of 2 and was also calculated for
      the prostate using an alpha/beta ratio of 6 and a urethral alpha/beta ratio of 2.
      The primary endpoints of this study were the prostate D90 BED (pD90BED) and
      urethral D30 BED normalized to the maximal potential prostate D90 BED (nuD30BED).
      RESULTS: The manual plan comparison (alpha/beta = 2) yielded no significant
      difference in the prostate D90 BED (median, 192 Gy2 for both isotopes). No
      significant difference was observed for the nuD30BED (median, 199 Gy2 and 202 Gy2
      for 125 I and 131 Cs, respectively). For the inverse planning simulated annealing
      plan comparisons (alpha/beta = 2), the prostate D90 BED was significantly lower
      with 131 Cs than with 125 I (median, 177 Gy2 vs. 187 Gy2, respectively; p =
      0.01). However, the nuD30BED was significantly greater with 131 Cs than with 125
      I (median, 192 Gy2 vs. 189 Gy2, respectively; p = 0.01). Both the manual and the
      inverse planning simulated annealing plans resulted in a significantly lower
      prostate D90 BED (p = 0.01) and significantly greater nuD30BED for 131 Cs (p =
      0.01), compared with 125 I, when the prostate alpha/beta ratio was 6 and the
      urethral alpha/beta ratio was 2. CONCLUSION: This report highlights the
      controversy in comparing the dose to both the prostate and the organs at risk
      with different radionuclides.

PMID- 18722276
TI  - Positioning accuracy in stereotactic radiotherapy using a mask system with added
      vacuum mouth piece and stereoscopic X-ray positioning.
AB  - PURPOSE: For cranial patients receiving stereotactic radiotherapy, we use the
      Exactrac stereoscopic X-ray system to optimize patient positioning. Patients are
      immobilized with the BrainLAB Mask System (BrainLAB, Feldkirchen, Germany). We
      have developed an adapter to this system that accommodates a vacuum mouth piece
      (VMP). Measurements with the Exactrac system have been performed to study the
      positioning accuracy after corrections with this system and to evaluate the
      accuracy of the VMP vs. the standard available upper jaw support (UJS). METHODS
      AND MATERIALS: Positioning results were collected for 20 patients with the UJS
      and 20 patients with the VMP, before treatment (1,122 fractions) and after
      treatment (400 fractions). For all 6 degrees of freedom the average, the random
      error and systematic error were calculated. RESULTS: The average vector length
      before and after correction with the Exactrac system was 2.1 +/- 1.2 mm and 0.7
      +/- 0.6 mm respectively for UJS and 1.7 +/- 0.7 mm and 0.4 +/- 0.4 mm for VMP.
      Interfraction positioning for translations was greatly improved after correction
      with the Exactrac system (p < 0.0005) and is better with VMP than with UJS (p =
      0.005). Outliers were greatly reduced. Interfraction rotations were significantly
      smaller for VMP. Intrafraction errors for vertical and longitudinal translations
      and for rotations were smaller for the VMP. CONCLUSIONS: Positioning correction
      using the Exactrac X-ray system greatly improves accuracy. Adding the VMP results
      in even better patient fixation and smaller rotations, making it a useful
      addition to the Mask System. Combined, this is a convenient and accurate
      alternative to invasive fixation methods.

PMID- 18722274
TI  - Intrafractional motion of the prostate during hypofractionated radiotherapy.
AB  - PURPOSE: To report the characteristics of prostate motion as tracked by the
      stereoscopic X-ray images of the implanted fiducials during hypofractionated
      radiotherapy with CyberKnife. METHODS AND MATERIALS: Twenty-one patients with
      prostate cancer who were treated with CyberKnife between January 2005 and
      September 2007 were selected for this retrospective study. The CyberKnife uses a
      stereoscopic X-ray system to obtain the position of the prostate target through
      the monitoring of implanted gold fiducial markers. If there is a significant
      deviation, the treatment is paused while the patient is repositioned by moving
      the couch. The deviations calculated from X-ray images acquired within the time
      interval between two consecutive couch motions constitute a data set. RESULTS:
      Included in the analysis were 427 data sets and 4,439 time stamps of X-ray
      images. The mean duration for each data set was 697 sec. At 30 sec, a motion >2
      mm exists in about 5% of data sets. The percentage is increased to 8%, 11%, and
      14% at 60 sec, 90 sec, and 120 sec, respectively. A similar trend exists for
      other values of prostate motion. CONCLUSIONS: With proper monitoring and
      intervention during treatment, the prostate shifts observed among patients can be
      kept within the tracking range of the CyberKnife. On average, a sampling rate of
      approximately 40 sec between consecutive X-rays is acceptable to ensure
      submillimeter tracking. However, there is significant movement variation among
      patients, and a higher sampling rate may be necessary in some patients.

PMID- 18722277
TI  - Quantification and visualization of charged particle range variations.
AB  - PURPOSE: Range variations during respiration affect the penetration of charged
      particle beams and can result in beam overshoot or undershoot to the target. We
      have developed analysis tools to quantify the water equivalent pathlength (WEL)
      variations resulting from respiration (WEL analyzer, Aqualyzer), as well as a
      data explorer to view WEL variations interactively. METHODS AND MATERIALS: The
      metrics to characterize and quantify penetration of a charged particle beam
      during respiration were calculated semiautomatically. The analysis involved the
      generation of images that (1) encode the radiologic pathlength across a beam's
      eye view image during the respiratory phase, (2) display the variation of the
      radiologic pathlength relative to a reference respiratory phase, (3) display
      isopenetration as a function of breathing, and (4) show range fluctuation images
      for a compensating bolus when applied to four-dimensional computed tomography.
      Additional quantities relevant to the analysis of charged particle beams in a
      breathing patient that are calculated include the beam overshoot volume and beam
      overshoot distance. These quantities are calculated as a function of time, gantry
      angle, and position. RESULTS: The software was applied to test cases to
      illustrate its utility in the analysis of range variations of charged particle
      beams in the treatment of lung tumors. CONCLUSION: WEL analysis is useful in the
      rapid assessment of range variations in the treatment of lung tumors and in
      determining the optimal gantry angle and respiratory gating window. The extension
      of encoding range fluctuations to a beam's eye view display is helpful in
      designing plans that are more robust in the presence of motion.

PMID- 18722278
TI  - Four-dimensional computed tomography-based treatment planning for intensity
      modulated radiation therapy and proton therapy for distal esophageal cancer.
AB  - PURPOSE: To compare three-dimensional (3D) and four-dimensional (4D) computed
      tomography (CT)-based treatment plans for proton therapy or intensity-modulated
      radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung,
      heart, and spinal cord and variations in target coverage and normal tissue
      sparing. METHODS AND MATERIALS: The IMRT and proton plans for 15 patients with
      distal esophageal cancer were designed from the 3D average CT scans and then
      recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor
      coverage and normal tissue sparing. RESULTS: Compared with IMRT, median lung
      volumes exposed to 5, 10, and 20 Gy and mean lung dose were reduced by 35.6%,
      20.5%, 5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%, 8.4%, 5%, and
      2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam
      proton plan was achieved at the expense of less conformity to the target
      (conformity index [CI], 1.99) and greater irradiation of the heart (heart-V40,
      41.8%) compared with the IMRT plan(CI, 1.55, heart-V40, 35.7%) or the three-beam
      proton plan (CI, 1.46, heart-V40, 27.7%). Target coverage differed by more than
      2% between the 3D and 4D plans for patients with substantial diaphragm motion in
      the three-beam proton and IMRT plans. The difference in spinal cord maximum dose
      between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to
      variations in stomach gas filling. CONCLUSIONS: Proton therapy provided
      significantly better sparing of lung than did IMRT. Diaphragm motion and stomach
      gas-filling must be considered in evaluating target coverage and cord doses.

PMID- 18722279
TI  - Utility of four-dimensional computed tomography for analysis of intrafractional
      and interfractional variation in lung volumes.
AB  - PURPOSE: To assess the viability of four-dimensional (4D) computed tomography
      (CT) in describing intrafractional and interfractional changes in lung volumes
      and to determine which breathing phase, if any, produces the most highly
      reproducible lung volumes among fractions. METHODS AND MATERIALS: Weekly 4D CT
      scans were acquired for 13 patients with non-small-cell lung cancer during a
      course of radiotherapy. Contours delineating the right lung, left lung, and total
      lung were obtained by adapting library models of the anatomic structures to the
      CT images and propagating them to all 10 respiratory phases represented in the 4D
      CT image data set. Lung volumes were calculated using software tools in a
      commercial radiation treatment-planning system and analyzed for interfractional
      volume reproducibility using t tests and for phase reproducibility using a phase
      dependent uncertainty curve across all patients. Probability (p) values of <0.05
      were considered to indicate significant differences in all comparisons. RESULTS:
      The average mean coefficient of variation of tidal volume across all patients was
      25.0%. The average standard deviation of tidal volumes was 5.7% relative to the
      lung volume at end-expiration. Total volumes measured at the 30% phase were 15%
      more consistent than those measured at end-inspiration (p = 0.03). CONCLUSIONS:
      Four-dimensional CT assesses lung volume with acceptable precision; but the
      technique was unable to accurately predict interfractional changes in lung volume
      because wide variations in intra- and interfractional breathing cause high
      uncertainties in 4D CT data acquisition. The most reproducible breathing phase
      seems to be at the 30-40% phase (just before end-expiration).

PMID- 18722280
TI  - The effect of transponder motion on the accuracy of the Calypso Electromagnetic
      localization system.
AB  - PURPOSE: To determine position and velocity-dependent effects in the overall
      accuracy of the Calypso Electromagnetic localization system, under conditions
      that emulate transponder motion during normal free breathing. METHODS AND
      MATERIALS: Three localization transponders were mounted on a remote-controlled
      turntable that could move the transponders along a circular trajectory at speeds
      up to 3 cm/s. A stationary calibration established the coordinates of multiple
      points on each transponder's circular path. Position measurements taken while the
      transponders were in motion at a constant speed were then compared with the
      stationary coordinates. RESULTS: No statistically significant changes in the
      transponder positions in (x,y,z) were detected when the transponders were in
      motion. CONCLUSIONS: The accuracy of the localization system is unaffected by
      transponder motion.

PMID- 18722281
TI  - In regard to fuller et Al.

PMID- 18722282
TI  - Prone-breast radiotherapy: too early for conclusions: in regard to Chino et Al.
      (Int j radiat oncol biol phys 2008;70:916-920).

PMID- 18722283
TI  - Radiobiologic parameters and local effect model predictions for head-and-neck
      squamous cell carcinomas exposed to high linear energy transfer ions: in regard
      to Beuve et al. (Int J Radiat Oncol Biol Phys, In Press).

PMID- 18722286
TI  - Prone positioning causes the heart to be displaced anteriorly within the thorax:
      implications for breast cancer treatment.

PMID- 18722288
TI  - Contouring carcinomas by FDG-PET: is the role of tumor biology underestimated? In
      regard to MacManus et al. (Int J Radiat Oncol Biol Phys 2008;71:2-4).

PMID- 18722290
TI  - Radiation-induced malignant gliomas: is there a role for reirradiation? In regard
      to Paulino et Al. (Int j radiat oncol biol phys epub 2008 feb 8).

PMID- 18722291
TI  - Intraoperative radiation therapy after radical prostatectomy: in regard to
      Saracino et Al. (Int j radiat oncol biol phys, in press).

PMID- 18722294
TI  - Primary cementless total hip arthroplasty for bony ankylosis in patients with
      ankylosing spondylitis.
AB  - We retrospectively reviewed 54 patients (92 hips) who underwent cementless total
      hip arthroplasty for bony ankylosis in ankylosing spondylitis between September
      1988 and 2002. The mean age of the patients was 25.5 years. The mean duration of
      follow-up was 8.5 years. The average preoperative Harris Hip Score of 49.5
      improved to 82.6 postoperatively. Postoperatively, 10 hips had mild to moderate
      pain. Anterior dislocation occurred in 4 (4.3%) hips, and sciatic nerve palsy in
      1 (1.1%) hip. Heterotopic ossification was seen in 12 patients; reankylosis rate
      was 0%. Thirteen (14%) arthroplasties were revised because of aseptic loosening.
      Kaplan-Meier survivorship analysis with revision as end point revealed 98.8%
      survival at 5 years and 85.8% survival at 8.5 years follow-up.

PMID- 18722295
TI  - Neuroma of the infrapatellar branch of the saphenous nerve a cause of reversible
      knee stiffness after total knee arthroplasty.
AB  - Injury of the infrapatellar branch of the saphenous nerve (ISN) may be caused by
      a surgical laceration or trauma about the knee and can result in formation of a
      painful neuroma. There has been no report of knee stiffness after a total knee
      arthroplasty secondary to a painful neuroma of the ISN. In this report, we
      present a patient with pain and severe stiffness of her knee after a total knee
      arthroplasty. A neuroma of the ISN was resected, and the pain as well as the
      stiffness of the knee resolved. A source of pain such as a neuroma should be
      considered as a cause of reversible knee stiffness or "pseudoarthrofibrosis"
      after a total knee arthroplasty.

PMID- 18722297
TI  - Prospective randomized clinical trial comparing hemiarthroplasty to total hip
      arthroplasty in the treatment of displaced femoral neck fractures: winner of the
      Dorr Award.
AB  - The Displaced Femoral (neck fracture) Arthroplasty Consortium for Treatment and
      Outcomes study is a prospective, multicenter randomized clinical trial comparing
      hemiarthroplasty to total hip arthroplasty (THA) in the treatment of displaced
      femoral neck fractures in previously independent patients. Primary outcomes were
      measured at 6, 12, and 24 months with the Short Form-36 (SF-36), Western Ontario
      and McMaster Osteoarthritis Index (WOMAC), and the Harris Hip Score and the Timed
      "Up & Go" Test. Forty subjects were enrolled. At 24 months, THA patients had
      significantly less pain on the SF-36 subscale than hemiarthroplasty patients
      (54.8 +/- 7.9 vs 44.7 +/- 10.5, P = .04) and scored significantly better on the
      SF-36 mental health subscale (54.9 +/- 9.4 vs 40.9 +/- 10.3, P = .006). Total hip
      arthroplasty patients also had superior WOMAC function scores (81.8 +/- 10.2 vs
      65.1 +/- 18.1, P = .03). Significant differences in outcomes, without a
      significantly greater incidence of complications, suggest THA is a valuable
      treatment option for the active elderly hip fracture population.

PMID- 18722298
TI  - Impact of payer type on resource utilization, outcomes and access to care in
      total hip arthroplasty.
AB  - The purpose of this study was to determine if Medicaid patients undergoing a
      primary total hip arthroplasty differed from Medicare and commercial-payer
      patients with respect to baseline demographic characteristics, social history,
      clinical outcomes, and resource utilization. A retrospective review of 224
      subjects who received a primary total hip arthroplasty at a single institution
      was conducted and stratified by insurance type. Baseline clinical and demographic
      information and functional outcomes were compared between Medicaid, Medicare, and
      commercial-payer patients. Medicaid patients had lower preoperative (P < .0001)
      and postoperative (P < .0001) Harris Hip Scores when compared with patients who
      have Medicare or commercial insurance. Medicaid patients also traveled twice as
      far to receive treatment (66.0 vs 38.3 miles). Decreased access to health care
      and increased time to presentation may account for the decreased functional
      scores and poorer clinical outcomes observed in Medicaid patients when compared
      with Medicare and commercially insured patients.

PMID- 18722299
TI  - Evaluation of deep venous thrombosis prophylaxis in low-risk patients undergoing
      total knee arthroplasty.
AB  - Our objective of the study was to address the question: "What is the efficacy of
      a deep venous thrombosis (DVT) and pulmonary embolus prophylaxis protocol after
      total knee arthroplasty (TKA) in which low-risk patients had only aspirin and
      mechanical devices for prophylaxis?" A multimodal approach to DVT prophylaxis
      using aspirin as the primary mode of chemoprophylaxis was successful in
      preventing DVT-related morbidity and mortality in 312 consecutive TKAs performed
      in low-risk patients. There were no DVT-related deaths and no deaths in general
      at 90 days of follow-up coupled with a low rate of readmission for thromboembolic
      events and no readmissions or reoperations from bleeding in this group. This low
      morbidity, low-cost prophylaxis should be considered an appropriate protocol for
      low-risk patients undergoing TKA. Of all TKAs performed during the time period of
      the study, 73% qualified for the low-risk group.

PMID- 18722300
TI  - Decreased venous thromboembolism with injectable vs oral anticoagulation after
      discharge for major orthopedic surgery.
AB  - The use of outpatient anticoagulation after major orthopedic surgery with oral or
      injectable anticoagulants is recommended by national guidelines. A retrospective
      analysis of medical and pharmacy claims data using the PharMetrics Patient
      Centric Database Inc, Watertown, Mass, was conducted. After adjusting for
      covariates, patients receiving warfarin were approximately 30% more likely to
      experience a venous thromboembolism than those receiving an injectable
      anticoagulant (6.3% vs 4.8%; adjusted odds ratio, 1.3; 95% confidence interval,
      1.1-1.5) by 30 days. The data at 90 days showed similar results. No significant
      differences in the incidence of major bleeding events between the cohorts were
      observed (incidence of major bleed <0.4%). These findings support the randomized
      controlled studies and expand the data to the real-world perspective. Clinicians
      should evaluate these data alongside the clinical trial data when selecting the
      safest and most effective prophylactic therapy for postdischarge anticoagulation.

PMID- 18722301
TI  - The use of spiral computed tomography scans for the detection of pulmonary
      embolism.
AB  - Total joint arthroplasty carries a risk of symptomatic pulmonary embolism (PE).
      This study examined symptoms and risk factors of patients who underwent
      postoperative spiral computed tomography (CT) scans. The presenting symptoms and
      risk factors of total hip arthroplasty and total knee arthroplasty patients who
      had a postoperative CT scan were reviewed and the location of PE/deep vein
      thrombosis (DVT) was noted for positive scans. Of the 10209 patients who had
      total hip or total knee arthroplasty, 478 (4.7%) underwent a spiral CT scan to
      rule out PE and 136 (1.3%) had scans positive for PE. Twenty-two and four tenths
      percent of scans were positive for PE only, 2.1% for proximal DVT only, and 6.1%
      for PE and proximal DVT. Patients taking estrogen and patients presenting with
      low oxygen saturation postoperatively were significantly (P = .010, P < .001)
      more likely to have a positive scan. Spiral CT is the gold standard for detection
      of PE. Thirty-one and one half percent of scans were positive for PE and/or DVT,
      yet only 19.2% of patients had a predisposing risk factor for PE. Total knee
      arthroplasty carried a greater risk for PE than THA.

PMID- 18722302
TI  - Causes of early failure in a multicenter clinical trial of hip resurfacing.
AB  - The purpose of this study was to evaluate the clinical outcomes and possible
      causes of early failure in a multicenter trial of metal-on-metal hip resurfacing.
      Two hundred patients were prospectively enrolled and followed for an average of
      31.2 months (range, 12-54 months). Of 200 patients, 14 (7.0%) required revision
      surgery at a mean time of 19.5 months (range, 3-47 months). Patients with
      failures were significantly younger and heavier than the nonfailures, and all
      were male. Patients who were revised did not differ from those who were not
      revised in terms of radiographic outcomes, but they did report lower functional
      outcome scores at all preoperative and postoperative testing intervals. Most
      failures (10/14) were related to early acetabular loosening. The learning curve
      was likely a factor in these cup failures. This report highlights the importance
      of patient selection and surgical technique in hip resurfacing arthroplasty. It
      is anticipated that further surgical experience will lead to a reduction in this
      high early failure rate.

PMID- 18722303
TI  - Wear performance of large-diameter differential-hardness hip bearings.
AB  - We hypothesized that differential-hardness hard-on-hard bearings would generate
      less wear debris compared with like-hardness metal-on-metal (M-o-M) bearings. We
      conducted wear testing on 3 types of large-diameter hard hip bearings: (1)
      contemporary cast-on-cast ("like" hardness) M-o-M; (2) differential-hardness M-o
      M; and (3) differential-hardness ceramic-on-metal. A simulated gait profile
      ranging from 200 to 2000 N was applied to the bearings at a frequency of 1 Hz for
      5 Mc. All bearings were tested in an anatomically inverted position in 90% alpha
      calf serum. Both differential-hardness bearing systems produced lower run-in wear
      rates (90%-97%), steady-state wear rate (45%-84%), and total metal wear (68%-88%)
      compared with the like-hardness bearing system. The ceramic-on-metal bearings
      exhibited the least wear followed by differential-hardness M-o-M bearings; like
      hardness M-o-M bearings exhibited the greatest amount of wear. These findings
      support our hypothesis that differential-hardness hip bearing systems produce
      less metallic wear debris than those with like hardness and may result in lower
      metal ion release in vivo.

PMID- 18722304
TI  - Effects of increased surgical volume on total knee arthroplasty complications.
AB  - The effect of increased total knee arthroplasty (TKA) surgical volume on the
      incidence of knee complications within a single surgeon's practice was
      determined. Data were collected prospectively on 600 primary TKAs. Major
      complications required knee reoperation. Minor complications were wound concerns
      requiring increased surveillance or oral antibiotics. Twelve major (2.0%) and 40
      minor (6.7%) complications occurred at minimum 2-year follow-up. Surgical volume
      increased from 57 to 150 procedures per 6 months through the course of the study.
      Multivariate analysis determined that increased surgical volume was associated
      with lower rates of both major and minor complications, adjusted odds ratio 0.62
      (95% confidence interval [CI], 0.40-0.96) and 0.56 (95% CI, 0.43-0.73),
      respectively. For each additional 50 procedures performed within a 6-month
      interval, major complications were reduced by 38% (P = .03), and minor
      complications were reduced by 44% (P < .0001). All complications were
      significantly decreased when the surgeon was performing 112 +/- 44 TKAs compared
      with 85 +/- 49 TKAs per 6-month interval.

PMID- 18722305
TI  - A randomized, prospective study of 3 minimally invasive surgical approaches in
      total hip arthroplasty: comprehensive gait analysis.
AB  - Purported advantages of total hip arthroplasty performed with minimally invasive
      surgical (MIS) approaches are less muscle damage and faster recovery. There are
      little data scientifically evaluating these claims. Twenty-four consecutive hips
      were randomized to total hip arthroplasty through 1 of 3 MIS approaches (2
      incision, mini-posterior, and mini-anterolateral). Each patient underwent
      preoperative and postoperative gait analysis. Gait parameters included vertical
      ground reaction force, velocity, single-leg stance time, limb-loading rate, and
      abductor torque. All 3 groups demonstrated overall improvements in gait
      parameters at 6 weeks postoperatively. The anterolateral approach patients showed
      a decrease in the vertical ground reaction force at mid-stance, whereas the 2
      incision and posterior approaches demonstrated no significant change. These
      results fail to demonstrate any significant advantage of the 2-incision approach
      over the posterior approach in kinetic gait parameters. Furthermore, the
      anterolateral approach demonstrates a gait pattern consistent with abductor
      muscle injury in the early recovery period, despite the MIS approach.

PMID- 18722306
TI  - Multimodal pain management and arthrofibrosis.
AB  - Pain control after arthroplasty has been a key concern for orthopedic surgeons.
      After total knee arthroplasty (TKA), a small group of patients developed a
      painful joint with suboptimal range of motion. Manipulation under anesthesia
      increases flexion and extension while decreasing pain in most cases. The
      objective of the present investigation is to asses the effect of a multimodal
      pain management protocol on arthrofibrosis in primary TKAs. A cohort of 1136
      patients who underwent primary TKA was selected. Patients were divided into 2
      groups: group A had 778 procedures performed using a traditional approach to pain
      control; group B included 358 procedures that received multimodal pain
      management. Group A had an incidence of manipulation of 4.75% (37/778). Of 357
      patients, 8 required manipulation in group B, which is an incidence of 2.24%. We
      recommend that orthopedic surgeons consider using a multimodal pain management
      protocol for TKA.

PMID- 18722307
TI  - High-impact sports after total knee arthroplasty.
AB  - Many patients will attempt high-impact loading activities after total knee
      arthroplasty. This study analyzed the clinical and radiographic results of these
      high-demand sports patients. A total of 31 patients (33 knees) were identified
      who participated in high-impact sports on average 4 times per week (range, 1-7
      times per week) for a mean of 3.5 hours per week (range, 1 to 10 hours),
      including jogging, downhill skiing, singles tennis, racquetball, squash, and
      basketball. At 4 years mean follow-up (range, 2-9 years), 32 of 33 knees had
      successful clinical and radiographic outcomes. Overall satisfaction was a mean of
      9.1 points on a scale of 0 to 10 points. These results indicate that some
      patients will participate in high-impact sports and enjoy excellent clinical
      outcomes at a minimum 4 years after surgery.

PMID- 18722308
TI  - Accuracy of knee range of motion assessment after total knee arthroplasty.
AB  - Measurement of knee joint range of motion (ROM) is important to assess after
      total knee arthroplasty. Our objective was to determine level of agreement and
      accuracy between observers with different knowledge on total ROM after total knee
      arthroplasty. Forty-one patients underwent x-ray of active and passive knee ROM
      (gold standard). Five different raters evaluated observed and measured ROM:
      orthopedic surgeon, clinical fellow, physician assistant, research fellow, and a
      physical therapist. A 1-way analysis of variance was used to determine
      differences in ROM between raters over both conditions. Limit of agreement for
      each rater for both active and passive total ROM under both conditions was
      calculated. Analysis of variance indicated a difference between raters for all
      conditions (range, P = .004 to P < or =.0001). The trend for all raters was to
      overestimate ROM at higher ranges. Assessment of ROM through direct observation
      without a goniometer provides inaccurate findings.

PMID- 18722309
TI  - The impact of diabetes on perioperative patient outcomes after total hip and
      total knee arthroplasty in the United States.
AB  - The purpose of this study was to determine whether patients with diabetes
      mellitus (DM) have a higher likelihood of immediate, inpatient complications
      following primary and revision total hip (THA) and total knee arthroplasty (TKA)
      than patients without DM. From 1988 to 2003, the Nationwide Inpatient Sample
      identified 751340 primary or revision THA or TKA patients. 64262 (8.55%) had DM.
      Comparisons of specific outcome measures between diabetic and nondiabetic cohorts
      were performed using bivariate and multivariate analyses with logistic regression
      modeling. Diabetic patients had fewer routine discharges and higher inflation
      adjusted hospital charges for all procedures. Although complications were not
      uniformly increased, diabetic patients had significantly increased odds of
      pneumonia, stroke, and transfusion (P < .001) after primary arthroplasty. This
      analysis of a large patient database indicates clinically relevant information
      for patients and surgeons, suggesting that patients undergoing THA and TKA
      demonstrate more complications and utilize more resources if they have the
      comorbidity of DM level II evidence.

PMID- 18722310
TI  - Implant migration and failure in total knee arthroplasty is related to body mass
      index and tibial component size.
AB  - Aseptic loosening of knee implants is multifactorial. The purpose of this study
      was to examine the role of body mass index and tibial component size on loosening
      and migration of total knee arthroplasty (TKA) implants. Six thousand five
      hundred forty-eight primary TKAs (anatomic graduated components) were studied
      with aseptic loosening as the end point. A second cohort of 81 TKAs (anatomic
      graduated components) had radiostereometric analysis beads implanted, permitting
      implant migration assessment. Patient mass and tibial component surface area were
      used to calculate potential tibial stresses. We found that higher potential
      stresses were associated with increased rates of loosening in both metal-backed
      and all-polyethylene designs. Increased tibial implant migration, in both the
      varus-valgus and anterior-posterior directions, was associated with higher
      estimated stresses. We found an increased rate of tibial component loosening and
      implant migration in patients with a higher mass and smaller tibial component
      size.

PMID- 18722311
TI  - In hospital complications after total joint arthroplasty.
AB  - Total joint arthroplasty is a safe and successful procedure. However, numerous
      complications may present after elective arthroplasty. This study prospectively
      collected data on systemic and local in hospital complications after 15383 joint
      arthroplasties, which included 8230 total hip arthroplasties and 7153 total knee
      arthroplasties. In general, the incidence of complications was higher after knee
      arthroplasty, simultaneous bilateral surgery, and revision surgery. There were 22
      (0.16%) deaths in this cohort. We identified 486 major systemic complications,
      the most common was pulmonary embolism (152), followed by tachyarrhythmia (92)
      and acute myocardial infarction (36). There were 109 major local complications,
      including 16 vascular injuries, 29 peripheral nerve injuries, 25 periprosthetic
      fractures, and 18 dislocations. Total joint arthroplasty, despite its success,
      can be associated with rare serious and life-threatening complications. This
      study provides a baseline of complications that can occur after elective joint
      arthroplasty.

PMID- 18722312
TI  - Generating an African palliative care evidence base: the context, need,
      challenges, and strategies.
AB  - The enormous burden of progressive, incurable disease in sub-Saharan Africa is
      reflected in the epidemiology of cancer and HIV. However, there has been little
      research activity and evidence generated to inform appropriate and effective
      responses. A collaborative of clinicians, academics and advocates have been
      active in the design, delivery and reporting of research activities in African
      palliative care. Here, they report the methodological, ethical, logistic and
      capacity-based challenges of conducting research in the sub-Saharan context from
      their experience. A number of strategies and responses are presented.

PMID- 18722313
TI  - Evidence supporting the use of two-hourly turning for pressure ulcer prevention.

PMID- 18722314
TI  - Pressure mapping and performance of the compression bandage/garment for venous
      leg ulcer treatment.
AB  - A study has been conducted on the commercially available compression bandages as
      regards their performance with time. Pressure mapping of these bandages has been
      done using a fabricated pressure-measuring device on a mannequin leg to see the
      effect on pressure due to creep, fabric friction and angle of bandaging. The
      results show that the creep behavior, frictional behavior and the angle of
      bandaging have a significant effect on the pressure profile generated by the
      bandages during application. The regression analysis shows that the surface
      friction restricts the slippage in a multilayer system. Also the diameters of the
      limb and the amount of stretch given to the bandage during application have
      definite impact on the bandage pressure. In case of compression garments, washing
      improves the pressure generated but not to the extent of the pressure of a virgin
      garment. Comparing the two compression materials i.e. bandage and garment, it is
      found that the presence of higher percentage of elastomeric material and a highly
      close construction in case of garment provides better holding power and a more
      homogeneous pressure distribution.

PMID- 18722315
TI  - Wound or disintegration complex: a theory of wound hybrids.

PMID- 18722316
TI  - Endocannabinoid system and wound healing.

PMID- 18722318
TI  - Cardiac resynchronization therapy improves renal function in human heart failure
      with reduced glomerular filtration rate.
AB  - BACKGROUND: Renal dysfunction is an important independent prognostic factor in
      heart failure (HF). Cardiac resynchronization therapy (CRT) improves functional
      status and left ventricular (LV) function in HF patients with ventricular
      dyssynchrony, but the impact of CRT on renal function is less defined. We
      hypothesized that CRT would improve glomerular filtration rate as estimated by
      the abbreviated Modification of Diet in Renal Disease equation (eGFR). METHODS
      AND RESULTS: The Multicenter InSync Randomized Clinical Evaluation (MIRACLE)
      study evaluated CRT in HF patients with NYHA Class III-IV, ejection fraction
      <or=35%, and QRS >or=130 ms. Patients were evaluated before and 6 months after
      randomization to control (n = 225) or CRT (n = 228). Patients were categorized
      according to their baseline eGFR: >or=90 (category A), 60 <or=eGFR <90 (category
      B), and 30 <or=eGFR <60 (category C) mL/min per 1.73 m(2). CRT improved LV
      function in all categories. Compared with control, CRT increased eGFR (-2.4 +/-
      1.2 vs. +2.7 +/- 1.2 mL/min per 1.73 m(2); P = .003) and reduced blood urea
      nitrogen (+6.4 +/- 2.4 vs. -1.1 +/- 1.5 mg/mL; P = .008) in category C, whereas
      no differences were observed in categories A and B. CONCLUSIONS: CRT increased
      eGFR and reduced blood urea nitrogen in HF patients with moderately reduced
      baseline eGFR. By improving cardiac function, CRT can indirectly improve renal
      function, underscoring the importance of cardiorenal interaction and providing
      another mechanism for the beneficial effects of CRT.

PMID- 18722319
TI  - Surgical ventricular restoration versus cardiac transplantation: a comparison of
      cost, outcomes, and survival.
AB  - BACKGROUND: Cardiac transplantation is the accepted standard treatment for end
      stage heart disease but is donor limited. Surgical ventricular remodeling is an
      established treatment for patients with ischemic cardiomyopathy. We sought to
      compare charges, outcomes, and survival in patients undergoing surgical
      ventricular restoration (SVR) versus cardiac transplantation (CTx). METHODS AND
      RESULTS: We retrospectively analyzed hospital charges, length of stay (LOS), and
      survival for 69 SVR and 53 CTx patients at our institution between January 2002
      and June 2005. We also compared New York Heart Association (NYHA) status and
      Kaplan-Meier survival of our SVR patients with CTx patients with ischemic
      cardiomyopathy from the International Society of Heart & Lung Transplantation
      (ISHLT) registry. Median total LOS (12 days vs. 17 days, P = .01) and median
      postoperative LOS (10 days vs. 15 days, P = .02) were shorter for SVR patients
      than our CTx patients. Median total hospital charges ($45,506 vs. $137,679, P <
      .0001) and median total drug charges ($2,625 vs. $15,930, P < .0001) were lower
      for SVR patients. Significant improvements in ejection fraction were seen after
      both SVR (27% vs. 37%; P < .0001) and CTx (14% vs. 62%, P < .0001). Furthermore,
      91% (49/54) of surviving SVR patients, 98% (44/45) of surviving CTx patients, and
      91% of ISHLT CTx patients improved to NYHA Class I/II at follow-up. Survival did
      not differ between groups. CONCLUSIONS: SVR patients demonstrate cost-effective
      clinical improvements that lead to good overall survival. SVR is an excellent
      surgical option for CHF patients who are not transplant candidates, and should be
      considered for ischemic cardiomyopathy patients who qualify for transplantation.
      This strategy may help relieve donor shortage and improve allocation of donor
      organs.

PMID- 18722320
TI  - Multiple neurohumoral modulating agents in systolic dysfunction heart failure:
      are we lowering blood pressure too much?
AB  - BACKGROUND: Disease-modifying drug treatment in heart failure (HF) reduces blood
      pressure. Titration of these agents is guided by clinic blood pressure readings;
      however, the impact of such treatment on blood pressure is unknown because
      diurnal blood pressure patterns remain poorly described. The aim of this study
      was to examine the impact of additional neurohumoral modulating agents on
      ambulatory blood pressure monitoring (ABPM) control in patients with systolic HF
      and examine the relationship between the burden of hypotension and clinical
      outcomes. METHODS AND RESULTS: In a prospective analysis on 45 patients
      undergoing initiation and optimization of additional medications (angiotensin
      converting enzyme inhibitors, angiotensin II receptor blockers, or beta
      blockers), mean daytime systolic (P = .035) and mean daytime and nocturnal
      diastolic hypotensive episodes (both P < .001) increased significantly
      posttitration. There was no change in clinic blood pressure before and after
      titration. In a cross-sectional analysis on 144 patients, those with the most
      diastolic hypotensive episodes had higher rates of HF readmissions (P = .01) and
      the composite end point of all-cause mortality and all-cause readmissions (P =
      .03). CONCLUSIONS: Additional neurohumoral modulating agents could produce
      significant increases in 24-hour hypotension burden despite reassuring clinic
      blood pressure readings. The burden of diastolic hypotension is independently
      predictive of HF readmissions and the composite end point of all-cause mortality
      and emergency readmissions.

PMID- 18722321
TI  - Association of blood pressure and its evolving changes with the survival of
      patients with heart failure.
AB  - OBJECTIVE: The association between low blood pressure (BP) levels and increased
      mortality has been established in several studies of heart failure (HF). Although
      many drugs administered to these patients decrease BP, the relationship between
      changes in BP and survival has not been investigated. Nor have previous analyses
      distinguished among different forms of death. We investigated the influence of
      baseline BP and changes in BP during a 1-year period on the survival of patients
      with HF, distinguishing among sudden cardiac death, nonsudden cardiac death, and
      noncardiac death. We also identified the possible relationship with the baseline
      values of and changes in other clinical and treatment variables, including
      pharmacologic treatments. METHOD AND RESULTS: A total of 1062 patients with
      chronic HF included in the Spanish National Registry of Sudden Death (mean age of
      64.5 +/- 11.8 years, 72% were men, and 21% were in New York Heart Association
      class III with a mean left ventricular ejection fraction of 36.7% +/- 14.2%) were
      prospectively investigated for a mean of 1.9 +/- 0.6 years. A multivariable Cox
      proportional hazards model adjusting for clinical and therapeutic variables
      showed an independent association between low baseline systolic blood pressure
      (SBP) and nonsudden cardiac death (hazard ratio [HR] 0.96, 95% confidence
      interval [CI] 0.93-0.98), but changes in SBP during the following year did not
      influence survival, regardless of the baseline SBP level (P = .55). Contrariwise,
      baseline diastolic BP was not associated with mortality, but an increase in
      diastolic BP during the following year showed a borderline independent
      significant association with lower nonsudden cardiac death (HR 0.90, 95% CI 0.82
      1.00). Treatment with angiotensin-converting enzyme inhibitors or beta-blockers
      at baseline was also associated with lower nonsudden cardiac mortality, as was an
      increase in left ventricular ejection fraction during the following year (HR
      0.69, 95% CI 0.51-0.93; P = .015). CONCLUSION: Among patients with stable HF, low
      SBP is associated with a greater risk of nonsudden cardiac death. The change in
      SBP during a 1-year period has no prognostic value. Because the beneficial
      effects of drugs associated with increased survival (in this study, angiotensin
      converting enzyme inhibitors and beta-blockers) thus seem to be independent of
      their effects on BP, changes in BP should probably not influence the decision to
      use such drugs or continue their administration.

PMID- 18722322
TI  - Noninvasive assessment of diastolic function in subjects with preserved left
      ventricular ejection fraction: usefulness of color kinetic imaging.
AB  - BACKGROUND: Noninvasive assessment of left ventricular (LV) diastolic function is
      not established in patients with preserved ejection fraction. We investigated a
      relation between diastolic function and diastolic wall dynamics. METHODS AND
      RESULTS: In the animal study, data were collected in hypertensive Dahl salt
      sensitive rats, a diastolic heart failure (DHF) model (n = 35), and normotensive
      Dahl rats (n = 26). In the clinical study, echocardiography was conducted in 26
      diabetic patients with normal ejection fraction and 10 age-matched controls. The
      diastolic index of color-encoded images (color kinesis diastolic index [CK-DI])
      was calculated as the ratio of LV cavity area expansion during the first 30% of
      diastolic filling time to that during the whole diastolic filling period. In the
      DHF model, the E/A ratio of the transmitral flow velocity curves was
      pseudonormalized with the development of heart failure, but CK-DI was not. CK-DI,
      not E/A, was significantly and inversely correlated with the time constant of LV
      relaxation. Angiotensin receptor blocker improved LV relaxation in the DHF model
      and increased CK-DI, but not E/A. The diabetic patients showed lower CK-DI than
      the controls, although E/A was not different. CONCLUSION: Color-encoded imaging
      is useful in evaluating LV diastolic function. The prevalence of LV diastolic
      dysfunction may have been clinically underestimated by the transmitral flow
      velocity curves.

PMID- 18722323
TI  - Computerized acoustic cardiographic electromechanical activation time correlates
      with invasive and echocardiographic parameters of left ventricular contractility.
AB  - BACKGROUND: Electromechanical activation time (EMAT) is a systolic time interval
      defined as the time from Q-wave onset to the peak first heart sound. We assessed
      the correlation between systolic dysfunction and EMAT calculated using
      computerized acoustic cardiography. METHODS: A total of 25 patients with heart
      failure contemporaneously underwent echocardiography, left-sided heart
      catheterization, and acoustic cardiography. Invasive pressure-volume hemodynamics
      included peak isovolumetric left ventricular (LV) pressure at the end-diastolic
      volume, end-diastolic pressure, dyssynchrony, and maximal +dP/dT. An EMAT/(R to R
      interval) (%EMAT) interval >or= 0.15 was prospectively defined as abnormal.
      RESULTS: An abnormal %EMAT correlated with a lower LV ejection fraction (50.9% +/
      18.6% with normal EMAT vs 32.0% +/- 10.9% with abnormal EMAT, P = .015), end
      systolic elastance (3.07 +/- 1.56 mm Hg/mL vs 1.43 +/- 0.83 mm Hg/mL, P = .018),
      and peak isovolumetric LV pressure at the end-diastolic volume (317 +/- 90 mm Hg
      vs 222 +/- 67 mm Hg, P = .015). An abnormal %EMAT was associated with a higher
      end-systolic volume index (33.6 +/- 29.3 mL/m(2) vs 71.0 +/- 35.8 mL/m(2), P =
      .011), end-diastolic volume index (61.2 +/- 29.8 mL/m(2) vs 100.3 +/- 40.8
      mL/m(2), P = .012), and dyssynchrony (26.1% +/- 6.0% vs 31.5% +/- 3.5%, P =
      .028). There was no difference in end-diastolic pressure (20.3 +/- 7.9 mm Hg vs
      21.4 +/- 12.3 mm Hg, P = .78). CONCLUSIONS: An abnormal %EMAT was strongly
      associated with impaired LV contractility but had no association with LV filling
      pressures. This noninvasive, simple, point-of-care diagnostic test has potential
      applications when echocardiography cannot be obtained in a timely fashion to
      assess systolic function.

PMID- 18722324
TI  - Echocardiography-guided pacemaker optimization and radial artery tonometry.
AB  - BACKGROUND: Biventricular (Biv) pacemaker optimization is underused because of
      time and echo skill required. We evaluated radial artery tonometry during echo
      guided Biv optimization of atrioventricular (AV) and interventricular (VV)
      delays. METHODS AND RESULTS: A total of 60 patients (67 +/- 10 years) underwent
      simultaneous radial artery tonometry and echocardiography after Biv implant at
      baseline, short AV delay, and optimal AV delay. Twenty of these also underwent VV
      optimization. Optimal AV delay was determined by ejection duration (E-dur) of
      left ventricular (LV) outflow tract by pulsed-waved (PW) Doppler (LV(E-dur)) and
      mitral inflow PW Doppler pattern and optimal VV delay by LV(E-dur) and tissue
      Doppler. E-dur was also measured from radial artery pulse wave (RA(E-dur)). AV
      optimization improved LV(E-dur) from 249 +/- 35 to 260 +/- 38 ms (P < .01) and
      RA(E-dur) from 276 +/- 31 ms to 284 +/- 32 ms (P = .02). Correlation between LV(E
      dur) and by RA(E-dur) was 0.83 (95% CI 0.75-0.92). RA(E-dur) was 282.53 +/- 30 at
      baseline, 286.65 +/- 36 at optimal AV delay (P < .04 vs. baseline) and 286.90 +/-
      35 ms (P < .04 vs. baseline) at optimal AV and VV delay in those who underwent VV
      optimization. CONCLUSIONS: AV and VV optimization by echocardiography produces
      significant improvement in LV(E-dur) and RA(E-dur). Radial artery tonometry may
      provide a simple noninvasive method to assist in AV delay optimization.

PMID- 18722325
TI  - The metabolic syndrome and mortality in an ethnically diverse heart failure
      population.
AB  - BACKGROUND: In the general population, 27% of adults have the metabolic syndrome
      (MetS) and is associated with increased mortality. Similar data are not available
      for a heart failure (HF) population. This study sought to determine the
      prevalence of the MetS and its effect on mortality in a HF population. METHODS
      AND RESULTS: Patients (n = 886) discharged from the hospital with a primary
      diagnosis of HF were retrospectively identified. Demographic, clinical, and
      laboratory data were extracted by chart review. The MetS was defined according to
      National Cholesterol Education Program Expert Panel criteria with a body mass
      index >or=30 kg/m(2) substituted for increased waist circumference. Mortality
      data were acquired by query of the National Death Index, with a median follow-up
      of 856 days. Data were available to evaluate for the presence or absence of MetS
      in 71% (n = 625). The prevalence of MetS in this cohort was 68%. MetS was most
      common in Hispanics (79%) compared with whites (70%) and blacks (61%, P = .003).
      Mortality was lower in those with MetS (44%) compared with those without (58%,
      unadjusted HR 0.67 [95% CI, 0.53-0.85]). In a fully adjusted model, there was
      still a significantly lower risk of mortality in those with MetS (adjusted HR
      0.73 [95% CI, 0.56-0.94]). CONCLUSIONS: In a cohort hospitalized with HF, the
      prevalence of MetS exceeds that of the general population, and unlike the general
      population, MetS is associated with a lower mortality.

PMID- 18722326
TI  - Skin-autofluorescence, a measure of tissue advanced glycation end-products
      (AGEs), is related to diastolic function in dialysis patients.
AB  - BACKGROUND: Diastolic dysfunction is a frequent cause of heart failure,
      particularly in dialysis patients. Advanced glycation end-products (AGEs) are
      increased in dialysis patients and are suggested to play a role in the
      development of diastolic dysfunction. The aim of our study was to assess whether
      AGE accumulation in dialysis patients is related to the presence of diastolic
      dysfunction. METHODS AND RESULTS: Data were analyzed from 43 dialysis patients,
      age 58 +/- 15 years, of whom 65% were male. Diastolic function was assessed using
      tissue velocity imaging (TVI) on echocardiography. Tissue AGE accumulation was
      measured using a validated skin-autofluorescence (skin-AF) reader. Plasma
      N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL)
      were measured by stable-isotope-dilution tandem mass spectrometry. Plasma
      pentosidine was measured by high-performance liquid chromatography. Skin-AF
      correlated with mean E' (r = -0.51, P < .001), E/A ratio (r = -0.39, P = .014),
      and E/E' (r = 0.38, P = .019). Plasma AGEs were not significantly associated with
      diastolic function. Multivariable linear regression analysis revealed that 54% of
      the variance of average E' was explained by age (P = .007), dialysis type (P =
      0.016), and skin-AF (P = .013). CONCLUSIONS: Tissue AGEs measured as skin-AF, but
      not plasma AGE levels, were related to diastolic function in dialysis patients.
      Although this may support the concept that tissue AGEs explain part of the
      increased prevalence of diastolic dysfunction in these patients, the ambiguous
      relation between plasma and tissue AGEs needs further exploring.

PMID- 18722328
TI  - Heart failure and diabetes mellitus: epidemiology and management of an alarming
      association.
AB  - Diabetes mellitus is a growing epidemic with a prevalence among patients with
      heart failure (HF) approaching 30%. Diabetes worsens the prognosis of HF, and the
      pathophysiology is complex and multifactorial. Early detection of subtle
      alterations in cardiac function by modern tools, such as Doppler echocardiography
      or brain natriuretic peptide dosage, is thus important in these patients. All
      drugs known to be effective in HF with systolic dysfunction are also effective in
      patients with diabetes. Angiotensin-converting enzyme inhibitors and angiotensin
      II receptor antagonists also seem particularly useful. Overall, however, little
      is known about the treatment of diabetic patients with HF, especially in case of
      preserved systolic function. Ongoing and future trials should help to determine
      the best treatment for these patients with or without associated diabetes. This
      review assesses the relationships between diabetes mellitus and HF and discusses
      the various medical strategies.

PMID- 18722329
TI  - What is the influence of renal function on the prognostic value of advanced
      glycation end-products and sRAGE in heart failure?

PMID- 18722327
TI  - Predictors of medication adherence using a multidimensional adherence model in
      patients with heart failure.
AB  - BACKGROUND: Medication adherence in heart failure (HF) is a crucial but poorly
      understood phenomenon. The purpose of this study was to explore factors
      contributing to medication adherence in patients with HF by using the World
      Health Organization's multidimensional adherence model. METHODS AND RESULTS:
      Patients (N = 134) with HF (70% were male, aged 61 +/- 12 years, 61% with New
      York Heart Association III/IV) were studied to determine the predictors of
      medication adherence derived from the multidimensional adherence model.
      Medication adherence was measured objectively using the medication event
      monitoring system for 3 months. Three indicators of adherence were assessed by
      the medication event monitoring system: 1) dose-count, the percentage of
      prescribed doses taken; 2) dose-days, the percentage of days the correct number
      of doses were taken; and 3) dose-time, the percentage of doses that were taken on
      schedule. Barriers to medication adherence, ethnicity, and perceived social
      support predicted dose-count (P < .001). New York Heart Association functional
      class, barriers to medication adherence, financial status, and perceived social
      support predicted dose-day (P < .001). Barriers to medication adherence and
      financial status predicted dose-time (P = .005). CONCLUSION: A number of
      modifiable factors predicted medication adherence in patients with HF, providing
      specific targets for intervention.

PMID- 18722331
TI  - Primary care of children and adolescents with Down syndrome: an update. Foreword.

PMID- 18722332
TI  - Primary care of children and adolescents with down syndrome: an update.

PMID- 18722334
TI  - Preface to the special issue on regulation of gene function.

PMID- 18722335
TI  - Wild and domesticated animals as reservoirs of Schistosomiasis mansoni in Brazil.
AB  - Natural infection with Schistosoma mansoni in wild vertebrates and domesticated
      animals in Brazil is described in this review from an epidemiological viewpoint.
      Some species of wild rodents are small-sized animals, with a short expectation of
      life, a limited territory, and present high infection rates under natural
      conditions. A successful maintenance of the parasite's life cycle under
      artificial conditions can be achieved with Biomphalaria glabrata. On the other
      hand, despite showing low natural infection rates, cattle are very susceptible to
      infection under experimental conditions (using calves of Holstein lineage, cross
      bred with the Gir lineage). Due to their large size (just one calf may harbor a
      number of worms higher than a whole colony of aquatic rodents) and their
      longevity, cattle are a potential reservoir for the maintenance and dissemination
      of the disease. There is thus a need of new studies to gain a better
      understanding about the actual role of these animals in the epidemiology of S.
      mansoni.

PMID- 18722336
TI  - Efficacy of the diamidine DB75 and its prodrug DB289, against murine models of
      human African trypanosomiasis.
AB  - The choice of drugs for the treatment of sleeping sickness is extremely limited.
      To redress this situation, the recently synthesised diamidine, 2,5-bis(4
      amidinophenyl)-furan (DB75, furamidine) and its methamidoxime prodrug, 2,5-bis(4
      amidinophenyl)-furan-bis-O-methylamidoxime (DB289, pafuramidine) were, together
      with pentamidine, evaluated for efficacy in acute rodent models. The activity was
      compared in three common mouse models that mimic the first stage of human African
      trypanosomiasis. The mice were infected with the pleomorphic T .b. rhodesiense
      strains KETRI2537 and STIB900 or with the monomorphic T. b. brucei strain
      STIB795. Importantly, DB75 showed activity superior to that of pentamidine at
      comparable doses in all three mouse models. Complete cures were achieved with
      oral dosing of the prodrug DB289 in all three models without any overt toxicity.
      This shows that the prodrug strategy was successful in terms of reducing toxicity
      and increasing efficacy and oral bioavailability.

PMID- 18722337
TI  - Egg yolk enhances early sporulation and toxicity of Bacillus sphaericus H5a5b for
      small-scale production of a mosquito control agent.
AB  - Bacillus sphaericus has been widely used in mosquito control programs, but the
      production of this bacterium is a little tricky as it does not utilize
      carbohydrates and requires proteinaceous substrates, which are expensive. In this
      study, we developed a cost-effective medium that resulted in a lower cost and
      shorter fermentation time. The locally available raw material, egg yolk was used
      and the level of sporulation, toxicity and biomass were compared with the
      conventional medium. Use of the egg yolk culture medium significantly shortened
      fermentation time to 15 h and yielded high activity, equivalent to that of
      conventional medium against 3rd instar Culex quinquefasciatus. Conventional NYSM
      medium required 21 h to attain the maximum activity and biomass. Hence, the egg
      yolk-based culture medium appears to be suitable and economical for the small
      scale production of B. sphaericus.

PMID- 18722338
TI  - An anaerobic bacterial MsrB model reveals catalytic mechanisms, advantages, and
      disadvantages provided by selenocysteine and cysteine in reduction of methionine
      R-sulfoxide.
AB  - We verified and generalized the catalytic features that selenocysteine (Sec) and
      cysteine (Cys) contribute to the reduction of methionine-R-sulfoxide using an
      anaerobic bacterial MsrB from Clostridium sp. OhILA as a model protein. The Sec
      containing Clostridium MsrB form exhibited 100-fold higher activity than its Cys
      containing form, revealing that Sec provided the catalytic advantage of higher
      activity. However, a resolving Cys was required for the thioredoxin (Trx)
      dependent recycling process of the Sec-containing form. Thus, Trx could reduce
      the selenenylsulfide bond, but its Trx-dependent recycling process was much less
      efficient compared to that for the disulfide bond in the Cys-containing form,
      demonstrating an obvious catalytic disadvantage. These data agreed well with our
      previous data on mammalian MsrBs, and therefore suggested that the catalytic
      mechanisms, as well as the catalytic advantages and disadvantages provided by the
      Sec and Cys residues, are most likely conserved from anaerobic bacteria to
      mammals. Taken together, we propose that the use of Sec in MsrB may depend on a
      balance between the catalytic advantage of higher activity and the disadvantage
      of a less efficient regeneration process provided by this residue.

PMID- 18722339
TI  - Isolation and characterization of Plasmodium falciparum UAP56 homolog: evidence
      for the coupling of RNA binding and splicing activity by site-directed mutations.
AB  - UAP56 (U2AF65 associated protein) is a member of the DEAD-box helicase family.
      Helicases are essential enzymes generally involved in the metabolism of nucleic
      acids. The gene encoding a member of DEAD-box family was cloned and characterized
      from the human malaria parasite Plasmodium falciparum. PfU52 is homologous to
      UAP56 and contains the RNA-dependent ATPase, RNA helicase and RNA binding
      activities. Using the parasite extract we report that PfU52 is involved in
      splicing reaction. Site-directed mutagenesis studies indicate that the conserved
      residues glycine 181, isoleucine 182 and arginine 206 are involved in RNA binding
      and this activity is required for the enzymatic activities of PfU52. PfU52 is
      expressed in all the intraerythrocytic developmental stages of the parasite. In
      the present study we have reported the detailed characterization of PfU52 from P.
      falciparum and these results advance the knowledge regarding the function of
      UAP56 in general.

PMID- 18722340
TI  - Modulation of a membrane lipid lamellar-nonlamellar phase transition by cationic
      lipids: a measure for transfection efficiency.
AB  - Synthetic cationic lipids can be used as DNA carriers and are regarded to be the
      most promising non-viral gene carriers. For this investigation, six novel
      phosphatidylcholine (PC) cationic derivatives with various hydrophobic moieties
      were synthesized and their transfection efficiencies for human umbilical artery
      endothelial cells (HUAEC) were determined. Three compounds with relatively short,
      myristoleoyl or myristelaidoyl 14:1 chains exhibited very high activity,
      exceeding by approximately 10 times that of the reference cationic derivative
      dioleoyl ethylPC (EDOPC). Noteworthy, cationic lipids with 14:1 hydrocarbon
      chains have not been tested as DNA carriers in transfection assays previously.
      The other three lipids, which contained oleoyl 18:1 and longer chains, exhibited
      moderate to weak transfection activity. Transfection efficiency was found to
      correlate strongly with the effect of the cationic lipids on the lamellar-to
      inverted hexagonal, Lalpha-->HII, phase conversion in dipalmitoleoyl
      phosphatidylethanolamine dispersions (DPoPE). X-ray diffraction on binary
      DPoPE/cationic lipid mixtures showed that the superior transfection agents
      eliminated the direct Lalpha-->HII phase transition and promoted formation of an
      inverted cubic phase between the Lalpha and HII phases. In contrast, moderate and
      weak transfection agents retained the direct Lalpha-->HII transition but shifted
      to higher temperatures than that of pure DPoPE, and induced cubic phase formation
      at a later stage. On the basis of current models of lipid membrane fusion,
      promotion of a cubic phase by the high-efficiency agents may be considered as an
      indication that their high transfection activity results from enhanced lipoplex
      fusion with cellular membranes. The distinct, well-expressed correlation
      established between transfection efficiency of a cationic lipid and the way it
      modulates nonlamellar phase formation of a membrane lipid could be useful as a
      criterion to assess the quality of lipid carriers and for rational design of new
      and superior nucleotide delivery agents.

PMID- 18722341
TI  - NMR investigations of interactions between anesthetics and lipid bilayers.
AB  - Interactions between anesthetics (lidocaine and short chain alcohols) and lipid
      membranes formed by dimyristoylphosphatidylcholine (DMPC) were studied using NMR
      spectroscopy. The orientational order of lidocaine was investigated using
      deuterium NMR on a selectively labelled compound whereas segmental ordering in
      the lipids was probed by two-dimensional 1H-13C separated local field experiments
      under magic-angle spinning conditions. In addition, trajectories generated in
      molecular dynamics (MD) computer simulations were used for interpretation of the
      experimental results. Separate simulations were carried out with charged and
      uncharged lidocaine molecules. Reasonable agreement between experimental dipolar
      interactions and the calculated counterparts was observed. Our results clearly
      show that charged lidocaine affects significantly the lipid headgroup. In
      particular the ordering of the lipids is increased accompanied by drastic changes
      in the orientation of the P-N vector in the choline group.

PMID- 18722342
TI  - Ryanoids and imperatoxin affect the modulation of cardiac ryanodine receptors by
      dihydropyridine receptor Peptide A.
AB  - Ca(2+)-entry via L-type Ca(2+) channels (DHPR) is known to trigger ryanodine
      receptor (RyR)-mediated Ca(2+)-release from sarcoplasmic reticulum (SR). The
      mechanism that terminates SR Ca(2+) release is still unknown. Previous reports
      showed evidence of Ca(2+)-entry independent inhibition of Ca(2+) sparks by DHPR
      in cardiomyocytes. A peptide from the DHPR loop II-III (PepA) was reported to
      modulate isolated RyRs. We found that PepA induced voltage-dependent "flicker
      block" and transition to substates of fully-activated cardiac RyRs in planar
      bilayers. Substates had less voltage-dependence than block and did not represent
      occupancy of a ryanoid site. However, ryanoids stabilized PepA-induced events
      while PepA increased RyR2 affinity for ryanodol, which suggests cooperative
      interactions. Ryanodol stabilized Imperatoxin A (IpTx(A)) binding but when
      IpTx(A) bound first, it prevented ryanodol binding. Moreover, IpTx(A) and PepA
      excluded each other from their sites. This suggests that IpTx(A) generates a
      vestibular gate (either sterically or allosterically) that prevents access to the
      peptides and ryanodol binding sites. Inactivating gate moieties ("ball peptides")
      from K(+) and Na(+) channels (ShakerB and KIFMK, respectively) induced well
      resolved slow block and substates, which were sensitive to ryanoids and IpTx(A)
      and allowed, by comparison, better understanding of PepA action. The RyR2 appears
      to interact with PepA or ball peptides through a two-step mechanism, reminiscent
      of the inactivation of voltage-gated channels, which includes binding to outer
      (substates) and inner (block) vestibular regions in the channel conduction
      pathway. Our results open the possibility that "ball peptide-like" moieties in
      RyR2-interacting proteins could modulate SR Ca(2+) release in cells.

PMID- 18722343
TI  - Nkx2-5- and Isl1-expressing cardiac progenitors contribute to proepicardium.
AB  - Correct delineation of the hierarchy of cardiac progenitors is a key step to
      understanding heart development, and will pave the way for future use of cardiac
      progenitors in the treatment of heart disease. Multipotent Nkx2-5 and Isl1
      cardiac progenitors contribute to cardiomyocyte, smooth muscle, and endothelial
      lineages, which constitute the major lineages of the heart. Recently, progenitors
      located within the proepicardium and epicardium were reported to differentiate
      into cardiomyocytes, as well as smooth muscle and endothelial cells. However, the
      relationship of these proepicardial progenitors to the previously described Nkx2
      5 and Isl1 cardiac progenitors is incompletely understood. To address this
      question, we performed in vivo Cre-loxP-based lineage tracing. Both Nkx2-5- and
      Isl1-expressing progenitors contributed to the proepicardium and expressed Wt1
      and Tbx18, markers of proepicardial progenitor cells. Interestingly, Nkx2-5
      knockout resulted in abnormal proepicardial development and decreased expression
      of Wt1, suggesting a functional role for Nkx2-5 in proepicardium formation. Taken
      together, these results suggest that Nkx2-5 and/or Isl1 cardiac progenitors
      contribute to proepicardium during heart development.

PMID- 18722344
TI  - BCAR3 regulates EGF-induced DNA synthesis in normal human breast MCF-12A cells.
AB  - BCAR3 (breast cancer anti-estrogen resistance 3) is a signal transducer
      containing an SH2 domain, a proline/serine-rich domain and a GDP-exchange factor
      homologous domain, whose role in signaling pathways is currently unclear.
      Furthermore, BCAR3 is implicated in anti-estrogen resistance of breast cancer
      cells. In the present study, we investigated the functional role of BCAR3 in a
      mitogenic signaling pathway of EGF in non-tumorigenic human breast epithelial MCF
      12A cells. Microinjection of an anti-BCAR3 antibody, siRNAs targeting BCAR3 and
      an SH2 domain of BCAR3 inhibited EGF-induced DNA synthesis. Direct association of
      BCAR3 with activated EGF receptor and Cas was observed. Lastly, microinjection of
      a BCAR3 expression plasmid induced DNA synthesis. These findings suggest that the
      BCAR3 protein, through its SH2 domain, is involved in the signaling pathways of
      EGF leading to cell cycle progression, and that BCAR3 itself is part of a
      mitogenic signaling pathway.

PMID- 18722345
TI  - Mycobacterium tuberculosis UsfX (Rv3287c) exhibits novel nucleotide binding and
      hydrolysis properties.
AB  - The Mycobacterium tuberculosis UsfX protein is an anti-sigma factor which
      regulates its cognate sigma factor SigF. UsfX shares low sequence homology with
      other anti-sigma factors making it difficult to identify the nucleotide binding
      site and characterize its properties. We have identified that the NTP binding
      site occurs close to Trp106 and the area around the nucleotide binding site is
      predominantly negatively charged. UsfX binds to a variety of nucleotides unlike
      other reported anti-sigma factors and exhibits an unusual dual NTPase activity.
      In silico computational experiments have identified a XGSFS motif close to the
      nucleotide binding site for metal ion binding. This motif is analogous to the
      DXSXS motif reported earlier in the human integrin CR3 protein superfamily.
      Overall, the experiments suggest that the M. tuberculosis UsfX represents a
      distinct anti-sigma factor family with a novel nucleotide binding motif.

PMID- 18722346
TI  - The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor
      agonist.
AB  - Nicotinic acid has been used for several decades to treat dyslipidemia. In mice,
      the lipid-lowing effect of nicotinic acid is mediated by the Gi coupled receptor
      PUMA-G. In humans, high (GPR109A) and low (GPR109B) affinity nicotinic acid
      receptors have been characterized. Here we identify monomethylfumarate as a
      GPR109A agonist. Monomethylfumarate is the active metabolite of the psoriasis
      drug Fumaderm. We show that monomethylfumarate activates GPR109A in a calcium
      based aequorin assay, cAMP assay and demonstrate competitive binding with
      nicotinic acid. We show that GPR109A is highly expressed in neutrophils and
      epidermal keratinocytes, and that its expression is increased in human psoriatic
      lesions. Our findings provide evidence that GPR109A is a target for the drug
      Fumaderm and suggest that niacin should be investigated to treat psoriasis in
      addition to its role in treating lipid disorders.

PMID- 18722347
TI  - Caveolae as potential mediators of MCH-signaling pathways.
AB  - The melanin-concentrating hormone receptor (MCHR) 1 is a G protein-coupled
      receptor involved in the regulation of appetite and energy expenditure in
      mammals. Here, we show that MCHR1 partitions to lipid rafts in stably expressing
      Chinese hamster ovary cells. In addition to co-fractionating with lipid rafts
      containing caveolin-1 on sucrose gradients, caveolin-1 was present in MCHR1
      immunoprecipitates, suggesting that MCHR1 complexes with caveolae. The
      cholesterol-depleting drug methyl-beta-cyclodextrin impaired MCH-mediated ERK
      signaling. These data suggest that a functional interaction between MCHR1 and
      caveolin-1 in lipid rafts exists and provide a basis for further biochemical
      studies to understand the significance on MCH-mediated signal transduction
      events.

PMID- 18722348
TI  - Concatameric cloning of porcine microRNA molecules after assembly PCR.
AB  - While the number of human or murine microRNAs (miRNAs) increases continuously,
      there are limited data available from other species. We report a novel
      identification method of small RNAs such as miRNAs, which allows simultaneous
      cloning of five RNA molecules within the same insert. First, RNA molecules <40nt
      were polyadenylated and five concatamerising 5' DNA adaptors were ligated to the
      molecules in independent reactions. Reverse transcription was carried out using
      oligo d(T)(18) primers with concatamerising 5' overhangs. The introduced
      complementary termini in the different reactions enabled the subsequent coupling
      of five purified antisense strands to one molecule by means of an assembly PCR.
      After cloning, small RNAs were identified by DNA sequencing. By means of this
      cloning approach, we identified 10 novel and one known porcine miRNAs.
      Furthermore, the endogenous expression of the cloned miRNAs was quantified in
      various tissues using a qRT-PCR approach.

PMID- 18722349
TI  - Low-resolution characterization of the 3D structure of the Euglena gracilis
      photoreceptor.
AB  - This paper deals with the first characterization of the structure of the
      photoreceptive organelle of the unicellular alga Euglena gracilis (Euglenophyta).
      This organelle has a three-dimensional organization consisting of up to 50
      closely stacked membrane lamellae. Ionically induced unstacking of the
      photoreceptor lamellae revealed ordered arrays well suited to structural analysis
      by electron microscopy and image analysis, which ultimately yielded a low
      resolution picture of the structure. Each lamella is formed by the photoreceptive
      membrane protein of the cell assembled within the membrane layer in a hexagonal
      lattice. The first order diffraction spots in the calculated Fourier transform
      reveals the presence of 6-fold symmetrized topography (better resolution about
      90A). The 2D and 3D structural data are very similar with those recently
      published on proteorodopsin, a membrane protein used by marine bacterio-plankton
      as light-driven proton pump. In our opinion these similarity indicate that a
      photoreceptive protein belonging to the same superfamily of proteorodopsin could
      form the Euglena photoreceptor.

PMID- 18722350
TI  - Trichoplax, the simplest known animal, contains an estrogen-related receptor but
      no estrogen receptor: Implications for estrogen receptor evolution.
AB  - Although, as their names imply, estrogen receptors [ERs] and estrogen-related
      receptors [ERRs] are related transcription factors, their evolutionary
      relationships to each other are not fully understood. To elucidate the origins
      and evolution of ERs and ERRs, we searched for their orthologs in the recently
      sequenced genome of Trichoplax, the simplest known animal, and in the genomes of
      three lophotrochozoans: Capitella, an annelid worm, Helobdella robusta, a leech,
      and Lottia gigantea, a snail. BLAST searches found an ERR in Trichoplax, but no
      ER. BLAST searches also found ERRs in all three lophotrochozoans and invertebrate
      like ERs in Capitella and Lottia, but not in Helobdella. Unexpectedly we find
      that the Capitella ER sequence is closest to ERbeta, unlike the other
      invertebrate ER sequences, which are closest to ERalpha. Our database searches
      and phylogenetic analysis indicate that invertebrate ERs evolved in a
      lophotrochozoan and steroid-binding ERs evolved in a deuterostome.

PMID- 18722351
TI  - Proteomics-based identification of autoantibody against CDC25B as a novel serum
      marker in esophageal squamous cell carcinoma.
AB  - This study was aimed to identify tumor proteins that elicit a humoral response in
      patients with esophageal squamous cell carcinoma (ESCC). Autologous sera of 15
      newly diagnosed patients with ESCC and age- and gender-matched 15 healthy
      controls were analyzed individually for antibody-based reactivity against
      proteins from 15 homogenized ESCC tissue mixture resolved by two-dimensional
      PAGE. One protein spot, which reacted with sera from ESCC patients but not with
      those from controls, was identified to be CDC25B by mass spectrometry and Western
      blotting. High expression of CDC25B was detected in ESCC cell lines and primary
      tumor tissues, but not in normal esophageal tissues. In addition, CDC25B
      expression was significantly higher in tumor tissue of patients with sera
      positive CDC25B-Abs than that of patients without CDC25B-Abs. Finally, anti
      CDC25B antibodies were readily detectable in sera from 45 of 124 (36.29%)
      patients with ESCC, 13 of 150 (8.67%) patients with other types of cancer and 0
      of 102 (0%) of healthy individuals. Thus, CDC25B autoantibodies may have clinical
      utility in ESCC screening and diagnosis.

PMID- 18722352
TI  - Expression and role of DJ-1 in leukemia.
AB  - DJ-1 is a multifunctional protein that has been implicated in pathogenesis of
      some solid tumors. In this study, we found that DJ-1 was overexpressed in acute
      leukemia (AL) patient samples and leukemia cell lines, which gave the first clue
      that DJ-1 overexpression might be involved in leukemogenesis and/or disease
      progression of AL. Inactivation of DJ-1 by RNA-mediated interference (RNAi) in
      leukemia cell lines K562 and HL60 resulted in inhibition of the proliferation
      potential and enhancement of the sensitivity of leukemia cells to
      chemotherapeutic drug etoposide. Further investigation of DJ-1 activity revealed
      that phosphatase and tensin homolog (PTEN), as well as some proliferation and
      apoptosis-related genes, was regulated by DJ-1. Thus, DJ-1 might be involved in
      leukemogesis through regulating cell growth, proliferation, and apoptosis. It
      could be a potential therapeutic target for leukemia.

PMID- 18722353
TI  - Acetylation of Sirt2 by p300 attenuates its deacetylase activity.
AB  - Histone deacetylases (HDACs) are subdivided into three classes--HDAC I, HDAC II,
      and Sir2. Sirt proteins are mammalian members of the Sir2 family of NAD+
      (nicotinamide adenine dinucleotide)-dependent protein deacetylases. The balance
      between acetylation and deacetylation of histone and non-histone proteins,
      regulated by protein acetyltransferases and deacetylases, affects the expression
      of genes involved in a variety of cellular processes. In addition, HDAC1 is
      acetylated and regulated by p300, a transcriptional co-activator with protein
      acetyltransferase activity, suggesting that protein acetyltransferases and
      deacetylases they control the activities of each other. Although the regulation
      of HDAC1 by p300 is well characterized, the relationship between Sir2 homologs
      and p300 is not understood. Here, we report that p300 interacts with Sirt2, a
      member of the Sir2 family, and triggers the acetylation and subsequent down
      regulation of the deacetylation activity of Sirt2, and that the acetylation of
      Sirt2 by p300 relieves the inhibitory effect of Sirt2 on the transcriptional
      activity of p53. These observations demonstrate that p300 can inactivate Sirt2 by
      acetylation and that p300 may regulate the activity of p53 indirectly through
      Sirt2 in addition to its direct modification of p53.

PMID- 18722354
TI  - Featural and configural face processing differentially modulate ERP components.
AB  - Since all faces share the same first-order configuration, individual faces are
      recognized by subtle differences in their individual features and second-order
      configuration. This study asked two questions about the ERP signatures of
      featural and configural face processing. First, which ERP components are
      sensitive to subtle modifications of features and second-order configuration?
      Secondly, does explicitly instructing participants to attend to either the
      features or the configuration of face stimuli influence the neural processes
      elicited by these stimuli? In the first part of this experiment, pairs of faces
      with differences in their features, in their second-order configuration or no
      difference were presented, with participants making same/different judgments. In
      the second part, participants were asked to focus on either the features or
      configuration in pairs of faces and to judge if there was any difference in that
      aspect while ignoring other differences. The P1 and N170 ERP components were not
      influenced by feature or second-order configuration differences in faces,
      indicating that these components could be more sensitive to manipulations that
      disrupt the first-order configuration of a face. In contrast, the P2 was larger
      in amplitude for faces with a configuration modification than for faces with a
      feature modification or for the original face. One explanation of these results
      is that processing the configuration of a face elicits more visual cortical
      feedback than processing the features. Finally, modulation of the P300 confirmed
      that the tasks presented in Part 2 were successful in varying the attention focus
      on the features or configuration.

PMID- 18722355
TI  - Protective effect of Ginkgolids (A+B) is associated with inhibition of
      NIK/IKK/IkappaB/NF-kappaB signaling pathway in a rat model of permanent focal
      cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: We have previously reported that Ginkgolids which contain
      Ginkgolids A and B (Ginkgolids (A+B), GKAB) reduce infarct size in a rat model of
      focal ischemia. NF-kappaB-inducing kinase (NIK)-IkappaBalpha kinase (IKK) pathway
      plays an important role in activation of nuclear factor kappaB (NF-kappaB). A
      previous study demonstrated that Ginkgolid B inhibited lipopolysaccharide (LPS)-
      and platelet activating factor (PAF)-induced NF-kappaB activation in rat pleural
      polymorphonuclear granulocytes. However, little is known about the inhibitory
      mechanisms of Ginkgolids on the activation of NF-kappaB. The present study
      evaluated the effects of GKAB on NIK/IKK/IkappaB/NF-kappaB signaling pathway in a
      rat model of permanent focal cerebral ischemia. METHODS: Rats were subjected to
      permanent middle cerebral artery occlusion (pMCAO) by intraluminal suture
      blockade. GKAB was injected intravenously (iv) immediately after ischemic onset.
      Western blot analysis was employed to determine alterations in IkappaBalpha,
      phosphorylated NIK (p-NIK) and phosphorylated IKKalpha (p-IKKalpha).
      Immunohistochemistry was used to confirm the nuclear translocation of NF-kappaB
      p65. RT-PCR was used to detect induction of NF-kappaB target gene c-Myc mRNA.
      RESULTS: The results showed a brief increase in p-NIK levels after ischemia. GKAB
      blocked ischemia-induced increases in p-NIK and p-IKKalpha levels, and reversed
      the decline in IkappaBalpha levels. Ischemia-induced nuclear translocation of NF
      kappaB p65 was attenuated by GKAB(.) GKAB also repressed the ischemia-induced
      increase in expression of NF-kappaB target gene c-Myc mRNA. CONCLUSIONS: These
      findings suggest that GKAB-mediated neuroprotective effect against ischemia
      appears to be associated with blocking NF-kappaB activation by suppressing the
      NIK-IKK pathway.

PMID- 18722356
TI  - Eye-movements and ERPs reveal the time course of processing negation and
      remitting counterfactual worlds.
AB  - The ability to update our current knowledge using contextual information is a
      vital process during every-day language comprehension. To understand a negated
      statement, readers are required to cancel real-world expectations, but are not
      explicitly provided with an alternative model. Thus, the question of how and when
      a negative context influences interpretation of later events arises. We report
      one eye-movement study (Exp. 1) and one ERP study (Exp. 2) investigating the
      effects of negation on discourse processing. Prior context depicted a real-world
      (RW), or negated-world (NW), while the second sentence was manipulated to create
      RW anomalous continuations, where events included a violation of RW knowledge,
      and RW-congruent continuations, where the events described were congruent with RW
      knowledge. Results from Experiment 1 showed that the negated discourse context
      did not influence initial processing of the target sentence, as reflected in
      participants' eye-movement behaviour. Similarly, Experiment 2 revealed that the
      typical N400 effect to semantic violations has not been reversed by introducing a
      negated-world context. However, in later processing, Experiment 1 demonstrated
      that the negated-world context is eventually incorporated into the representation
      of the sentence meaning. Thus, we suggest that discourse does not always have an
      immediate effect on language comprehension and discuss the results in terms of a
      variety of accounts of representing negation.

PMID- 18722357
TI  - Immunohistochemical localization of CB1 cannabinoid receptors in frontal cortex
      and related limbic areas in obese Zucker rats: effects of chronic fluoxetine
      treatment.
AB  - In the present study, we report on the application of two specific polyclonal
      antibodies to different intracellular domains of the CB1 cannabinoid receptor to
      define the expression of the neural CB1 cannabinoid receptor at the histochemical
      level in frontal cortex and related limbic areas of the obese Zucker rats. Higher
      levels of CB1 receptor expression in frontal, cingulated and piriform cortex,
      without differences in temporal, parietal and occipital cortex, were observed in
      obese Zucker rats, with respect to their lean littermates. CB1 phosphorylated
      receptor (CB1-P) levels were also higher in frontal, temporal, parietal and
      occipital cortex in obese rats with respect to lean controls. Potential
      involvement of brain cortical CB1 cannabinoid receptors in the long-term effects
      of fluoxetine was studied. Experimental animals were administered with fluoxetine
      (10 mg/kg, i.p.) daily for 3 weeks, whereas the control group was given 0.9% NaCl
      solution. In obese Zucker rats, a significant decrease in CB1 receptor levels,
      measured by western blot, was observed in brain cortex after fluoxetine
      treatment. Immunostaining for CB1 receptor expression was also carried out,
      showing a significant decrease in the density of neural cells positive for CB1
      receptor in frontal, cingulate and piriform cortex, without changes in parietal,
      temporal and occipital regions. Regional prosencephalic immunostaining for CB1-P
      receptor level showed a significant decrease in the density of stained neural
      cells in frontal, temporal and parietal cortex, without changes in cingulated,
      piriform and occipital cortex. These results suggest the involvement of
      endocannabinoid system in the chronic effects of fluoxetine, especially in the
      frontal cortex.

PMID- 18722358
TI  - Does kainic acid induce partial brain lesion in an invertebrate model: sepia
      officinalis? Comparison with electrolytic lesion.
AB  - The present study investigates the feasibility of excitotoxic lesions in the
      cuttlefish in the mapping of brain functions in Cephalopods. Adult animals were
      injected locally with a neurotoxin, kainic acid. The brain region receiving the
      neurotoxin was the vertical lobe, a key brain structure for learning and memory
      processes. Brain damage induced by these injections was evaluated using different
      histological stainings: hematoxilin-eosin, Fink-Heimer and DAPI. The results were
      compared with histological changes after electrolytic lesion of the vertical
      lobe. Neurodegeneration was revealed in and around the injection site: an intense
      area of proliferative cells, degenerating terminal axon ramifications and cell
      death. In comparison with electrolytic lesion, excitotoxic lesion displays
      important advantages, since fibres of passage are not destroyed by kainic acid
      injection, which induces only a restricted lesion and so is an appropriate method
      of investigating the role of the vertical lobe or other brain regions in a
      Cephalopod model, Sepia officinalis.

PMID- 18722359
TI  - Optimization of a therapeutic protocol for intravenous injection of human
      mesenchymal stem cells after cerebral ischemia in adult rats.
AB  - The systemic injection of human mesenchymal stem cells (hMSCs) prepared from
      adult bone marrow has therapeutic benefits after cerebral artery occlusion in
      rats, and may have multiple therapeutic effects at various sites and times within
      the lesion as the cells respond to a particular pathological microenvironment.
      However, the comparative therapeutic benefits of multiple injections of hMSCs at
      different time points after cerebral artery occlusion in rats remain unclear. In
      this study, we induced middle cerebral artery occlusion (MCAO) in rats using
      intra-luminal vascular occlusion, and infused hMSCs intravenously at a single 6 h
      time point (low and high cell doses) and various multiple time points after MCAO.
      From MRI analyses lesion volume was reduced in all hMSC cell injection groups as
      compared to serum alone injections. However, the greatest therapeutic benefit was
      achieved following a single high cell dose injection at 6 h post-MCAO, rather
      than multiple lower cell infusions over multiple time points. Three-dimensional
      analysis of capillary vessels in the lesion indicated that the capillary volume
      was equally increased in all of the cell-injected groups. Thus, differences in
      functional outcome in the hMSC transplantation subgroups are not likely the
      result of differences in angiogenesis, but rather from differences in
      neuroprotective effects.

PMID- 18722361
TI  - Neuronal injury induces the release of pro-interleukin-1beta from activated
      microglia in vitro.
AB  - Microglia activated after brain injury, are a major source of the pro
      inflammatory cytokine interleukin-1 (IL-1), which is known to further exacerbate
      damage. However, the mechanisms that control IL-1 release in acute neuronal
      injury are unknown and the purpose of this study was to test the hypothesis that
      neuronal injury induces IL-1beta release from microglial cells. Here we report
      that lipopolysaccharide (LPS)-activated rat microglia co-cultured with healthy
      rat neurons express pro-IL-1beta, which in the absence of cell death accumulates
      in the cells. Treatment of co-cultures with the excitotoxin N-methyl-D-aspartate
      (NMDA) induced neuronal cell death leading to the appearance of pro-IL-1beta in
      the culture supernatant. This effect was reversed by the NMDA receptor antagonist
      MK-801, and was neuron-dependent, since NMDA had no effect on cell death or pro
      IL-1beta release in mixed glial cell cultures. In addition, we show that pro-IL
      1beta release from LPS-treated mixed glia or LPS-treated microglia is
      significantly reduced in the presence of conditioned medium from healthy co
      cultures or neuronal cultures respectively. These results demonstrate that
      injured neurons promote the release of pro-IL-1beta from microglia, possibly by
      regulating microglial cell viability, and suggest an important alternative
      mechanism of IL-1beta release that occurs in response to neuronal injury.

PMID- 18722360
TI  - Inactivation of median preoptic nucleus causes c-Fos expression in hypocretin-
      and serotonin-containing neurons in anesthetized rat.
AB  - The median preoptic nucleus (MnPN) of the hypothalamus contains sleep-active
      neurons including sleep-active GABAergic neurons and is involved in the
      regulation of nonREM/REM sleep. The hypocretinergic (HCRT) neurons of the
      perifornical-lateral hypothalamic area (PF-LHA) and serotonergic (5-HT) neurons
      of the dorsal raphe nucleus (DRN) are mostly active during waking and have been
      implicated in the regulation of arousal. MnPN GABAergic neurons project to the PF
      LHA and DRN. It is hypothesized that MnPN promotes sleep by inhibiting multiple
      arousal systems including HCRT and other wake-active neurons within the PF-LHA
      and 5-HT neurons in the DRN. We examined the effects of inactivation of MnPN
      neurons by locally microinjecting 0.2 microl of 1 mM or 10 mM solutions of a
      GABA(A) receptor agonist, muscimol, into the MnPN on Fos expression (Fos-IR) in
      the PF-LHA neurons including HCRT neurons and 5-HT neurons in the DRN in
      anesthetized rats. Compared to artificial cerebrospinal fluid control,
      microinjection of muscimol into the MnPN resulted in significantly higher
      percentages of HCRT and non-HCRT neurons in the PF-LHA and 5-HT neurons in the
      DRN that exhibited Fos-IR. The percentage of melanin-concentrating hormone
      (MCH)+/Fos+ neurons in the PF-LHA did not change after muscimol treatments. These
      results support a hypothesis that the activation of MnPN neurons contributes to
      the suppression of wake-promoting systems including HCRT and other unidentified
      neurons in the PF-LHA and 5-HT neurons in the DRN. These results also suggest
      that MCH neurons may not be under MnPN inhibitory control. These findings are
      consistent with a hypothesized role of MnPN in sleep regulation.

PMID- 18722362
TI  - Protective effect of unsymmetrical dichalcogenide, a novel antioxidant agent, in
      vitro and an in vivo model of brain oxidative damage.
AB  - Unsymmetrical dichalcogenides, a class of organoselenium compounds, were screened
      for antioxidant activity in rat brain homogenates in vitro. Unsymmetrical
      dichalcogenides (1-3) were tested against lipid peroxidation induced by sodium
      nitroprusside (SNP) or malonate, and reactive species (RS) production induced by
      sodium azide in rat brain homogenates. Compounds 1 (without a substituent at the
      phenyl group), 2 (chloro substituent at the phenyl group bounded to the sulfur
      atom) and 3 (chloro substituent at the phenyl group bounded to the selenium atom)
      protected against lipid peroxidation induced by SNP. The IC50 values followed the
      order 3<2<1. Lipid peroxidation induced by malonate was also reduced by
      dichalcogenides 1, 2 and 3. The IC50 values were 3<or=2<1. RS production induced
      by sodium azide was reduced by compounds 1-3 (IC50 values were 3<2<or=1).
      Compounds 1-3 were screened against oxidatively modified protein in rat brain
      homogenates. Compound 3 presented the lowest value of IC50 23.5 microM (IC50
      values were 3<2<or=1). Compounds 1-3 at 40 microM displayed thiol peroxidase-like
      activity in rat brain homogenates. Since compound 3 was the most efficient
      antioxidant against lipid and protein oxidation in rat brain homogenates in
      vitro, 3 was investigated in the oxidative damage induced by SNP in mouse brain.
      Swiss albino mice were pre-treated with compound 3 (50 mg/kg, oral route, p.o).
      After 30 min, mice received SNP (0.35 microM/site i.c.v.). The levels of lipid
      peroxidation and the activity of catalase, glutathione peroxidase (GPx),
      glutathione S-transferase (GST) and glutathione reductase (GR) were carried out
      in brain homogenates of SNP-injected mice. Compound 3 protected against the
      increase in lipid peroxidation levels and the reduction of GST and GR activities
      in brain homogenate of mice exposed to SNP, suggesting the potential beneficial
      activity of dichalcogenides against deleterious oxidations in an in vivo model.

PMID- 18722363
TI  - Association between CAPN10 UCSNP-43 gene polymorphism and polycystic ovary
      syndrome in Chilean women.
AB  - BACKGROUND: Studies have suggested that the Calpain-10 gene polymorphisms may
      play a role in polycystic ovary syndrome (PCOS) susceptibility. Thus, the aim of
      the present study was to evaluate the possible association between three single
      nucleotide polymorphisms (SNPs) in the calpain-10 gene (UCSNPs -43, -19, and -63)
      and polycystic ovary syndrome (PCOS) in Chilean women. METHODS: Fifty women with
      PCOS (28.8+/-8.2 y) and 70 healthy women (28.6+/-8.6 y) were included in this
      study. Serum lipids, hormonal status, fasting glucose, oral glucose tolerance
      test (OGTT), insulin, HOMAIR, and uric acid levels were determined by
      conventional methods. The calpain-10 gene variants were detected by PCR and PCR
      RFLP, respectively. RESULTS: The presence of uncommon allele (A) for the UCSNP-43
      was associated with increased risk of PCOS (odds ratio=1.93, 95% CI: 1.11-3.34).
      The UCSNP-63 (OR=1.11, 95% CI: 0.59-2.11) and UCSNP-19 (OR=0.93, 95% CI: 0.55
      1.57) were not associated to PCOS. However, the PCOS women carrying the CC
      genotype for UCSNP-63 exhibited higher values of total cholesterol and LDL-C
      (P<0.05). Similarly, control women carrying the CC genotype showed higher serum
      levels of triglycerides, HDL-C and uric acid (P<0.05). CONCLUSION: Our data
      suggest the contribution of CAPN10 UCSNP-43 gene polymorphism to PCOS in Chilean
      women. However, further studies with larger samples are necessary to confirm this
      observation.

PMID- 18722364
TI  - Multicentric evaluation of the homogeneous LDL-cholesterol Plus assay: comparison
      with beta-quantification and Friedewald formula.
AB  - OBJECTIVES: To evaluate the analytical and clinical performance of a new version
      of the LDL-C Plus assay and compare it with the beta-quantification (BQ) method
      in a multicenter study. DESIGN AND METHODS: Direct LDL-C was measured in 169
      fresh pooled samples and in 830 clinical samples with known LDL-C by BQ. The
      reactivity of lipoproteins and the effect of hemoglobin, bilirubin and
      chylomicrons (CM) were studied. RESULTS: Direct LDL-C total imprecision was
      <2.2%; inaccuracy <+/-2.5% (unaffected by triglycerides up to 9.5 mmol/L); and
      total error 9.8%. Direct assay reacted with 95%, 50% and 25% of the cholesterol
      in the LDL, intermediate (IDL) and VLDL fractions, respectively. A significant
      association was observed with BQ. Icteric samples showed a negative bias and the
      effect of CM was variable. A positive bias was observed when VLDL
      cholesterol/triglyceride ratio was >0.57. CONCLUSIONS: LDL-C Plus assay
      represents a valid alternative to BQ for clinical laboratories.

PMID- 18722365
TI  - Ionizing radiation-induced gene modulations, cytokine content changes and
      telomere shortening in mouse fetuses exhibiting forelimb defects.
AB  - Several lines of evidence have linked limb teratogenesis to radiation-induced
      apoptosis and to the p53 status in murine fetuses. In previous reports, we
      studied the occurrence of various malformations after intrauterine irradiation
      and showed that these malformations were modulated by p53-deficiency as well as
      by the developmental stage at which embryos were irradiated. In this new study,
      we focused onto one particular phenotype namely forelimb defects to further
      unravel the cellular and molecular mechanisms underlying this malformation. We
      measured various parameters expected to be directly or indirectly influenced by
      irradiation damage. The mouse fetuses were irradiated at day 12 p.c. (post
      conception) and examined for forelimb defects on gestational days 15, 16, 17 and
      19 of development. The release of inflammatory cytokines was determined in the
      amniotic fluid on day 16 p.c. and the mean telomere lengths assessed at days 12,
      13 and 19 p.c. Differential gene expression within the forelimb bud tissues was
      determined using Real Time quantitative PCR (RTqPCR) 24 h following irradiation.
      Apoptosis was investigated in the normal and malformed fetuses using the TUNEL
      assay and RTqPCR. First, we found that irradiated fetuses with forelimb defects
      displayed excessive apoptosis in the predigital regions. Besides, overexpression
      of the pro-apoptotic Bax gene indicates a mitochondrial-mediated cell death.
      Secondly, our results showed overexpression of MKK3 and MKK7 (members of the
      stress-activated MAP kinase family) within the malformed fetuses. The latter
      could be involved in radiation-induced apoptosis through activation of the p38
      and JNK pathways. Thirdly, we found that irradiated fetuses exhibiting forelimb
      defects showed a marked telomere shortening. Interestingly, telomere shortening
      was observed as the malformations became apparent. Fourthly, we measured cytokine
      levels in the amniotic fluid and detected a considerable inflammatory reaction
      among the irradiated fetuses as evidenced by the increase in pro-inflammatory
      cytokine levels. Altogether, our data suggest that transcriptional modulations of
      apoptotic, inflammation, stress, and DNA damage players are early events in
      radiation-induced forelimb defects. These changes resulted in harsh developmental
      conditions as indicated by a marked increase in cytokine levels in the amniotic
      fluid and telomere shortening, two features concomitant with the onset of the
      forelimb defect phenotype in our study.

PMID- 18722366
TI  - Effect of pyrrolidine dithiocarbamate on hepatic vascular stress gene expression
      during ischemia and reperfusion.
AB  - Pyrrolidine dithiocarbamate, an antioxidant and a potent inhibitor of nuclear
      factor-kappa B (NF-kappaB), is known to have protective effect against ischemia
      and reperfusion injury. This study examined the cytoprotective mechanism of
      pyrrolidine dithiocarbamate against the microcirculatory failure caused by
      hepatic ischemia and reperfusion. Rats were subjected to 60 min of hepatic
      ischemia followed by 5 h of reperfusion. Pyrrolidine dithiocarbamate (100 mg/kg)
      or the vehicle was administered intraperitoneally 24 h before ischemia. The level
      of serum aminotransferases and hepatic lipid peroxides significantly increased,
      and the glutathione contents fell in the ischemia/reperfusion group. Pyrrolidine
      dithiocarbamate prevented the increase in the level of serum enzymes and hepatic
      lipid peroxides, and the decrease in the glutathione contents. The NF-kappaB DNA
      binding activity was inhibited by a pre-treatment with pyrrolidine
      dithiocarbamate. Ischemia and reperfusion significantly increased the mRNA
      expression of the endothelin-1 and endothelin ET(B) receptor, which was prevented
      by pyrrolidine dithiocarbamate. There were significant increases in the mRNA
      expressions of inducible nitric oxide synthase, tumor necrosis factor-alpha, and
      cyclooxygenase-2, in the livers after ischemia and reperfusion. These increases
      were attenuated by the pyrrolidine dithiocarbamate treatment. In a rat model of
      hepatic ischemia and reperfusion, our results suggest that the hepatoprotective
      actions of pyrrolidine dithiocarbamate may be mediated in part through the
      modulation of imbalanced expression of vascular stress genes.

PMID- 18722368
TI  - Oxidative injury to blood vessels and glia of the pre-laminar optic nerve head in
      human glaucoma.
AB  - Glaucoma is a leading cause of irreversible world blindness. Oxidative damage and
      vascular injury have been implicated in the pathogenesis of this disease. The
      purpose of this study was to determine in human primary open angle glaucoma
      whether oxidative injury occurs in pre-laminar optic nerve blood vessels and
      glial cells. Following IRB approval, sections from post-mortem primary open angle
      glaucoma eyes (n=5) with mean age of 77 +/- 9 yrs (+/-SD) were compared to normal
      control eyes (n=4) with mean age 70 +/- 9 yrs (Eye Bank of Canada).
      Immunostaining with nitrotyrosine, a footprint for peroxynitrite-mediated injury,
      was performed and sections were double-labeled with markers for vascular
      endothelial cells, perivascular smooth muscle cells, and astrocytes with CD34,
      smooth muscle actin (SMA), and glial fibrillary acidic protein (GFAP),
      respectively. Immunostaining was captured in a masked fashion using confocal
      microscopy, and defined regions of interest for blood vessels and glial tissue.
      Intensity measurements of supra-threshold area in pixels as percent of the total
      number of pixels were calculated using ImageJ (NIH) and compared using two-tailed
      Mann-Whitney nonparametric tests between glaucoma and control groups.
      Colocalization coefficients with cell-specific markers were determined and
      compared with random coefficients of correlation. Increased nitrotyrosine
      immunoreactivity was observed in pre-laminar optic nerve head blood vessels of
      primary open angle glaucoma eyes compared to controls and this difference was
      statistically significant (1.35 +/- 1.11% [+/-SD] vs. 0.01 +/- 0.01%, P=0.016).
      NT-immunoreactivity was also increased in the glial tissue surrounding the pre
      laminar optic nerve head in the glaucoma group and compared to controls, and this
      difference was statistically significant (18.37 +/-12.80% vs. 0.08 +/- 0.04%,
      P=0.016). Colocalization studies demonstrated nitrotyrosine staining in vascular
      endothelial and smooth muscle cells, in addition to astrocytes. Correlation
      coefficients for CD34, SMA, and GFAP were 0.37, 0.52, and 0.64, respectively.
      Oxidative injury is present in blood vessels and astrocytes in the pre-laminar
      optic nerve head in human primary open angle glaucoma. Peroxynitrite-mediated
      oxidative injury, whether primary or secondary, may contribute to the
      pathobiology of glaucoma disease.

PMID- 18722367
TI  - The isolation of novel mesenchymal stromal cell chemotactic factors from the
      conditioned medium of tumor cells.
AB  - Bone marrow-derived mesenchymal stromal cells (MSCs) localize to solid tumors.
      Defining the signaling mechanisms that regulate this process is important in
      understanding the role of MSCs in tumor growth. Using a combination of
      chromatography and electrospray tandem mass spectrometry we have identified novel
      soluble signaling molecules that induce MSC chemotaxis present in conditioned
      medium of the breast carcinoma cell line MDA-MB231. Previous work has employed
      survey strategies using ELISA assay to identify known chemokines that promote MSC
      chemotaxis. While these studies provide valuable insights into the intercellular
      signals that impact MSC behavior, many less well-described, but potentially
      important soluble signaling molecules could be overlooked using these methods.
      Through the less directed method of column chromatography we have identified
      novel candidate MSC chemotactic peptides. Two proteins, cyclophilin B and
      hepatoma-derived growth factor were then further characterized and shown to
      promote MSC chemotaxis.

PMID- 18722369
TI  - Statins decrease chondroitin sulfate proteoglycan expression and acute astrocyte
      activation in central nervous system injury.
AB  - Statins elicit numerous favorable effects on central nervous system (CNS) injury,
      including inhibition of the rhoA/ROCK pathway. In the present study, we show that
      statins decrease acute astrocyte activation in CNS injury, and decrease
      chondroitin sulfate proteoglycan (CSPG) levels in astrocyte cultures as well as
      CNS injury. CSPG levels decreased by up to 45% in simvastatin-treated astrocyte
      cultures compared to control cultures. In simvastatin-treated animals, CSPG
      levels declined by 60% 8 days after brain stab injury, and by 62-64% 4 weeks
      after spinal cord injury (SCI). Glial fibrillary acid protein (GFAP) levels
      decreased in brain stab at 8 days after surgery/intervention, suggesting that
      statins produce a decrease in astrocyte activation. Attenuation of astrocyte
      activation may contribute to the decline in CSPG levels. However, there are
      likely other contributing factors, since GFAP levels were not a contributing
      factor in the decline of CSPG levels in astrocyte cultures. Robust locomotor
      improvements were not observed with any treatment. The numerous beneficial
      effects of statins on CNS injury render them an attractive candidate in the
      treatment of CNS injury.

PMID- 18722370
TI  - Cigarette smoking products suppress anti-viral effects of Type I interferon via
      phosphorylation-dependent downregulation of its receptor.
AB  - While negative effect of smoking on the resistance to viral infections was known,
      the underlying mechanisms remained unclear. Here we report that products of
      cigarette smoking compromise the cellular anti-viral defenses by inhibiting the
      signaling induced by Type I interferon (IFN). Cigarette smoking condensate (but
      not pure nicotine) stimulated specific serine phosphorylation-dependent
      ubiquitination and degradation of the IFNAR1 subunit of the Type I IFN receptor
      leading to attenuation of IFN signaling and decreased resistance to viral
      infection. This resistance was restored in cells where phosphorylation-dependent
      degradation of IFNAR1 is abolished. We conclude that smoking compromises cellular
      anti-viral defenses via degradation of Type I IFN receptor and discuss the
      significance of this mechanism for efficacy of IFN-based therapies.

PMID- 18722371
TI  - A novel toxin-antitoxin operon talA/B from the Gram-positive bacterium Leifsonia
      xyli subsp. cynodontis.
AB  - Here we report a toxin-antitoxin (TA) operon talAB identified from the Gram
      positive bacterium Leifsonia xyli subsp. cynodontis. It is shown that talB
      encodes a broad-host cytotoxin functioning in different Gram-positive bacteria,
      while talA encodes its antidote. TalA and TalB form different hetero-oligomers in
      vitro; these hetero-oligomers, but not the antitoxin TalA, strongly bind to the
      talAB promoter region containing two inverted repeats. This represents a new
      mechanism of binding the promoter of a TA operon by the toxin and antitoxin
      complexes.

PMID- 18722372
TI  - Spectroscopic microvascular blood detection from the endoscopically normal
      colonic mucosa: biomarker for neoplasia risk.
AB  - BACKGROUND & AIMS: We previously used a novel biomedical optics technology, 4
      dimensional elastically scattered light fingerprinting, to show that in
      experimental colon carcinogenesis the predysplastic epithelial microvascular
      blood content is increased markedly. To assess the potential clinical
      translatability of this putative field effect marker, we characterized the early
      increase in blood supply (EIBS) in human beings in vivo. METHODS: We developed a
      novel, endoscopically compatible, polarization-gated, spectroscopic probe that
      was capable of measuring oxygenated and deoxygenated (Dhb) hemoglobin
      specifically in the mucosal microcirculation through polarization gating.
      Microvascular blood content was measured in 222 patients from the endoscopically
      normal cecum, midtransverse colon, and rectum. If a polyp was present, readings
      were taken from the polyp tissue along with the normal mucosa 10-cm and 30-cm
      proximal and distal to the lesion. RESULTS: Tissue phantom studies showed that
      the probe had outstanding accuracy for hemoglobin determination (r(2) = 0.99).
      Augmentation of microvasculature blood content was most pronounced within the
      most superficial ( approximately 100 microm) layer and dissipated in deeper
      layers (ie, submucosa). EIBS was detectable within 30 cm from the lesion and the
      magnitude mirrored adenoma proximity. This occurred for both oxygenated
      hemoglobin and DHb, with the effect size being slightly greater for DHb. EIBS
      correlated with adenoma size and was not engendered by nonneoplastic
      (hyperplastic) polyps. CONCLUSIONS: We show, herein, that in vivo microvascular
      blood content can be measured and provides an accurate marker of field
      carcinogenesis. This technological/biological advance has numerous potential
      applications in colorectal cancer screening such as improved polyp detection and
      risk stratification.

PMID- 18722374
TI  - Portal hypertension and primary biliary cirrhosis: effect of long-term
      ursodeoxycholic acid treatment.
AB  - BACKGROUND & AIMS: Portal hypertension can complicate primary biliary cirrhosis,
      but studies evaluating the direct measurement of the portohepatic gradient (PHG)
      are rare. The aim of the study was to determine the prevalence and prognostic
      value of portal hypertension in patients treated with ursodeoxycholic acid.
      METHODS: A total of 132 patients from a local "PBC clinic" were enrolled in this
      cohort study. The PHG and biochemical values were measured at inclusion and every
      2 years. Factors associated with survival were analyzed. RESULTS: Mean PHG at
      inclusion was 7.2 +/- 5.8 mm Hg. It was higher than normal (6 mm Hg) in 46
      patients (34.9%) and higher than 12 mm Hg (variceal bleeding risk limit) in 26
      patients (19.7%). There was a difference between the 3 subgroups in the
      probability of survival free of liver transplantation (P < .0003). After 2 years
      of treatment, a decreased or stable PHG (hazard ratio, 4.64; 95% confidence
      interval, 2.01-10.72) and normalization of aspartate aminotransferase (AST) level
      (hazard ratio, 2.89; 95% confidence interval, 1.03-8.05) were predictive of
      better survival on multivariate analysis. "Responders" (stable or improved PHG
      and normalized AST level at 2 years) have a 15-year survival similar to that of a
      control Quebec female population. CONCLUSIONS: Significant portal hypertension is
      a common complication of primary biliary cirrhosis. Changes in the PHG and
      normalized AST level after 2 years of ursodeoxycholic acid treatment can be used
      to identify a subgroup of responders with survival comparable to that of a
      control population.

PMID- 18722373
TI  - E2F1 inhibits c-Myc-driven apoptosis via PIK3CA/Akt/mTOR and COX-2 in a mouse
      model of human liver cancer.
AB  - BACKGROUND & AIMS: Resistance to apoptosis is essential for cancer growth. We
      previously reported that hepatic coexpression of c-Myc and E2F1, 2 key regulators
      of proliferation and apoptosis, enhanced hepatocellular carcinoma (HCC)
      development in transgenic mice. Here, we investigated the molecular mechanisms
      underlying oncogenic cooperation between c-Myc and E2F1 in relationship to human
      liver cancer. METHODS: Activation of pro- and antiapoptotic cascades was assessed
      by immunoblotting in experimental HCC models and in human HCC. Effect of
      antisense oligodeoxy nucleotides against c-Myc and E2F1 was studied in human HCC
      cell lines. Suppression of catalytic subunit p110alpha of phosphatidylinositol 3
      kinase (PIK3CA)/Akt, mammalian target of rapamycin (mTOR), and cyclooxygenase
      (COX)-2 pathways was achieved by pharmacologic inhibitors and small interfering
      RNA in human and mouse HCC cell lines. RESULTS: Coexpression with E2F1 did not
      increase proliferation triggered by c-Myc overexpression but conferred a strong
      resistance to c-Myc-initiated apoptosis via concomitant induction of
      PIK3CA/Akt/mTOR and c-Myb/COX-2 survival pathways. COX-2 was not induced in c-Myc
      and rarely in E2F1 tumors. In human HCC, PIK3CA/Akt/mTOR and c-Myb/COX-2 pathways
      were similarly activated, with levels of PIK3CA/Akt, mTOR, and c-Myb being
      inversely associated with patients' survival length. Silencing c-Myc and E2F1
      reduced PIK3CA/Akt and mTOR and completely abolished c-Myb and COX-2 expression
      in human HCC cell lines. Finally, simultaneous inhibition of PIK3CA/Akt/mTOR and
      COX-2 activity in in vitro models caused massive apoptosis of neoplastic
      hepatocytes. CONCLUSIONS: E2F1 may function as a critical antiapoptotic factor
      both in human and in rodent liver cancer through its ability to counteract c-Myc
      driven apoptosis via activation of PIK3CA/Akt/mTOR and c-Myb/COX-2 pathways.

PMID- 18722375
TI  - Lactobacillus crispatus M247-derived H2O2 acts as a signal transducing molecule
      activating peroxisome proliferator activated receptor-gamma in the intestinal
      mucosa.
AB  - BACKGROUND & AIMS: Accumulating evidence indicates that the peroxisome
      proliferator activated receptor (PPAR)-gamma is a major player in maintaining
      intestinal mucosa homeostasis, but whether PPAR-gamma is directly involved in
      probiotic-mediated effects and the molecular events involved in its activation
      are not known. METHODS: We investigated the role of PPAR-gamma in the
      immunomodulatory effects of Lactobacillus crispatus M247 on intestinal epithelial
      cells (IEC) and the role of probiotic-derived H(2)O(2) on PPAR-gamma activity.
      RESULTS: L crispatus M247 supplementation in mice significantly increased PPAR
      gamma levels and transcriptional activity in the colonic mucosa. L crispatus M247
      induced PPAR-gamma nuclear translocation and enhanced transcriptional activity in
      epithelial (CMT-93) cells, as demonstrated by the increased luciferase activity
      of a PPAR-gamma-responsive element, PPAR-gamma-responsive gene up-regulation, and
      reduced activity of an nuclear factor-kappaB-responsive element. Pharmacologic
      PPAR-gamma inhibition or silencing by small interfering RNA cancelled the L
      crispatus M247-mediated effects in CMT-93 cells. Because Lactobacillus strains
      producing little H(2)O(2) failed to activate PPAR-gamma, we investigated the role
      of L crispatus M247-derived H(2)O(2) in PPAR-gamma activation. L crispatus M247
      induced a transient rise in intracellular H(2)O(2) and PPAR-gamma transcriptional
      activity was cancelled by antioxidant or H(2)O(2) scavenger. Toll-like receptor
      (TLR)-2 was not required for PPAR-gamma up-regulation mediated by L crispatus
      M247 in mice, although the protective effects of L crispatus M247 on dextran
      sodium sulfate-induced colitis were less pronounced in TLR-2(-/-) mice.
      CONCLUSIONS: L crispatus M247 uses H(2)O(2) as a signal transducing molecule to
      induce PPAR-gamma activation in IEC, directly modulating epithelial cell
      responsiveness to inflammatory stimuli.

PMID- 18722376
TI  - Achalasia: a new clinically relevant classification by high-resolution manometry.
AB  - BACKGROUND & AIMS: Although the diagnosis of achalasia hinges on demonstrating
      impaired esophagogastric junction (EGJ) relaxation and aperistalsis, 3 distinct
      patterns of aperistalsis are discernable with high-resolution manometry (HRM).
      This study aimed to compare the clinical characteristics and treatment response
      of these 3 subtypes. METHODS: One thousand clinical HRM studies were reviewed,
      and 213 patients with impaired EGJ relaxation were identified. These were
      categorized into 4 groups: achalasia with minimal esophageal pressurization (type
      I, classic), achalasia with esophageal compression (type II), achalasia with
      spasm (type III), and functional obstruction with some preserved peristalsis.
      Clinical and manometric variables including treatment response were compared
      among the 3 achalasia subtypes. Logistic regression analysis was performed using
      treatment success as the dichotomous dependent variable controlling for
      independent manometric and clinical variables. RESULTS: Ninety-nine patients were
      newly diagnosed with achalasia (21 type I, 49 type II, 29 type III), and 83 of
      these had sufficient follow-up to analyze treatment response. Type II patients
      were significantly more likely to respond to any therapy (BoTox [71%], pneumatic
      dilation [91%], or Heller myotomy [100%]) than type I (56% overall) or type III
      (29% overall) patients. Logistic regression analysis found type II to be a
      predictor of positive treatment response, whereas type III and pretreatment
      esophageal dilatation were predictive of negative treatment response.
      CONCLUSIONS: Achalasia can be categorized into 3 subtypes that are distinct in
      terms of their responsiveness to medical or surgical therapies. Utilizing these
      subclassifications would likely strengthen future prospective studies of
      treatment efficacy in achalasia.

PMID- 18722377
TI  - HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level
      and risk of hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Our aims were to study the virologic, histologic, and clinical
      outcome in chronic hepatitis B (CHB) patients with hepatitis B surface antigen
      (HBsAg) seroclearance. METHODS: We determined the age of HBsAg seroclearance that
      is associated with a lower risk for hepatocellular carcinoma (HCC) in 298 CHB
      patients (median follow-up, 108 months). The following virologic and histologic
      features were also determined: liver stiffness (n = 229), liver histology, serum
      HBV DNA levels over time (n = 265), intrahepatic HBV DNA with covalently closed
      circular DNA (cccDNA) levels, and messenger RNA (mRNA) expression. RESULTS: The
      median age of HBsAg seroclearance was 49.6 years. Seven (2.4%) patients developed
      HCC. Cumulative risk for HCC was higher in patients with HBsAg seroclearance at
      ages >or=50 years compared with those with HBsAg seroclearance at ages <50 (P =
      .004) years. Of these 2 groups of patients, 29.5% and 7.9%, respectively, had
      significant fibrosis by liver stiffness measurement (P = .001), and 15.4% of
      patients had mild histologic fibrosis. Intrahepatic total HBV DNA and cccDNA were
      detected in 100% and 79.3% of patients, respectively. All patients had
      undetectable surface and precore/pregenomic RNA transcripts. One (9.1%) patient
      had X mRNA expression. Serum HBV DNA were detectable in 13.4%, 6.1%, and 3.7% of
      patients within 1 year and 5-10 and >10 years after HBsAg seroclearance,
      respectively, and 82.1% patients had persistently normal alanine aminotransferase
      levels. CONCLUSIONS: HBV persisted at low replicative and transcriptional levels
      after HBsAg seroclearance. HBsAg seroclearance at age <50 years was associated
      with a lower risk for the development of HCC.

PMID- 18722378
TI  - An investigation into the role of prostaglandins in zebrafish oocyte maturation
      and ovulation.
AB  - This study explored the potential for ovarian-derived prostaglandins (PGs) to be
      involved in the regulation of oocyte maturation and ovulation in zebrafish. It
      was demonstrated that cultured vitellogenic follicles have the capacity to
      produce prostaglandin E(2) (PGE(2)) and PGF(2alpha) in response to arachidonic
      acid (AA) in a concentration-dependent manner, and that AA stimulates the in
      vitro production of 17beta-estradiol (E(2)). The production of AA-stimulated
      PGF(2alpha) was significantly reduced by treatment with the non-selective
      cyclooxygenase (COX) inhibitor, indomethacin (INDO). Treatment of full-grown
      follicles with AA did not induce oocyte maturation as assessed by germinal
      vesicle breakdown, but INDO significantly decreased the rate of spontaneous
      maturation. Using Real-Time PCR, it was shown that follicles of different
      developmental size classes (primary growth and pre-vitellogenic, early
      vitellogenic, and mid- to full-grown vitellogenic) express enzymes that release
      (cytosolic phospholipase A(2) (cPLA(2)); phospholipase Cgamma1) or metabolize
      (COX-1, COX-2, and prostaglandin synthase-2) AA to PG metabolites. The expression
      of cPLA(2) was found to be significantly greater in full-grown follicles compared
      to follicles of the pre- and early-vitellogenic stages. In vivo studies
      demonstrated that breeding groups of zebrafish exposed to 100 microg/L INDO
      exhibited reduced spawning rates and clutch sizes compared with control and 1
      microg/L INDO exposed fish. In other studies, it was shown that naturally
      spawning groups of females exhibit increased ovarian levels of PGF(2alpha), E(2),
      and 17alpha,20beta-dihydroxy-4-pregnen-3-one (a maturation-inducing hormone in
      zebrafish) near the time of ovulation compared with non-breeding females.
      Collectively, these experiments indicate that the AA pathway in zebrafish ovaries
      is involved in the regulation of oocyte maturation and ovulation and a non
      selective inhibitor of COX disrupts these processes.

PMID- 18722379
TI  - Field tests of cis-regulatory variation at the prairie vole avpr1a locus:
      association with V1aR abundance but not sexual or social fidelity.
AB  - The neuropeptide vasopressin and its receptor V1aR are broadly implicated in
      social behavior and play a central role in several key aspects of male mating
      tactics in voles. In the prairie vole, a microsatellite in the cis-regulatory
      region of the gene encoding V1aR (avpr1a) provides a potential genetic basis for
      individual variation in neural phenotype and behavior; recent studies found that
      allele length predicts V1aR expression and male social attachment in the
      laboratory. Here, we explore the relationship between avpr1a microsatellite
      length, V1aR neural phenotype, and field measures of monogamy and fitness in male
      prairie voles. We found significant effects of allele length on V1aR expression
      in structures integral to pairbond formation. These effects did not, however,
      translate to differences in mating tactics or reproductive success. Together,
      these data suggest that, while length polymorphism in the avpr1a microsatellite
      influences neuronal phenotype, this variation does not contribute significantly
      to male reproductive success and field behavior. We propose that previously
      reported behavioral effects may be mediated primarily by sequence variation at
      this locus, for which allele length is an imperfect proxy. By combining genetic,
      neuronal and ecological approaches, these data provide novel insights into the
      contribution of genotype to natural diversity in brain and behavior.

PMID- 18722382
TI  - Cryo-EM structure of the yeast ATP synthase.
AB  - We have used electron cryomicroscopy of single particles to determine the
      structure of the ATP synthase from Saccharomyces cerevisiae. The resulting map at
      24 A resolution can accommodate atomic models of the F(1)-c(10) subcomplex, the
      peripheral stalk subcomplex, and the N-terminal domain of the oligomycin
      sensitivity conferral protein. The map is similar to an earlier electron
      cryomicroscopy structure of bovine mitochondrial ATP synthase but with important
      differences. It resolves the internal structure of the membrane region of the
      complex, especially the membrane embedded subunits b, c, and a. Comparison of the
      yeast ATP synthase map, which lacks density from the dimer-specific subunits e
      and g, with a map of the bovine enzyme that included e and g indicates where
      these subunits are located in the intact complex. This new map has allowed
      construction of a model of subunit arrangement in the F(O) motor of ATP synthase
      that dictates how dimerization of the complex via subunits e and g might occur.

PMID- 18722381
TI  - Rheb activates protein synthesis and growth in adult rat ventricular
      cardiomyocytes.
AB  - The mammalian target of rapamycin complex 1 (mTORC1), a key regulator of protein
      synthesis, growth and proliferation in mammalian cells, is implicated in the
      development of cardiac hypertrophy. Ras homolog enriched in brain (Rheb)
      positively regulates mTORC1. We have studied whether Rheb is sufficient to
      activate mTOR signaling and promote protein synthesis and cardiac hypertrophy in
      adult rat ventricular cardiomyocytes (ARVC). Rheb was overexpressed via an
      adenoviral vector in isolated ARVC. Overexpression of Rheb in ARVC activated
      mTORC1 signaling, several components of the translational machinery and
      stimulated protein synthesis. Our direct visualization approach to determine ARVC
      size revealed that overexpression of Rheb also induced cell growth and indeed did
      so to similar extent to the hypertrophic agent, phenylephrine (PE). Despite
      potent activation of mTORC1 signaling, overexpression of Rheb did not induce
      expression of the cardiac hypertrophic marker mRNAs for brain natriuretic peptide
      and atrial natriuretic factor, while PE treatment did markedly increase their
      expression. All the effects of Rheb were blocked by rapamycin, confirming their
      dependence on mTORC1 signaling. Our findings reveal that Rheb itself can activate
      both protein synthesis and cell growth in ARVC and demonstrate the key role
      played by mTORC1 in the growth of cardiomyocytes.

PMID- 18722380
TI  - Nitric oxide signaling and the regulation of myocardial function.
AB  - Nitric oxide, which is produced endogenously within cardiac myocytes by three
      distinct isoforms of nitric oxide synthase, is a key regulator of myocardial
      function. This review will focus on the regulation of myocardial function by each
      nitric oxide synthase isoform during health and disease, with a specific emphasis
      on the proposed end-targets and signaling pathways.

PMID- 18722383
TI  - The crystal structure of the C-terminal DAP5/p97 domain sheds light on the
      molecular basis for its processing by caspase cleavage.
AB  - DAP5/p97 (death-associated protein 5) is a member of the eukaryotic translation
      initiation factor 4G family. It functions as a scaffold protein promoting cap
      independent translation of proteins. During apoptosis, DAP5/p97 is cleaved by
      caspases at position 792, yielding an 86-kDa C-terminal truncated isoform
      (DAP5/p86) that promotes translation of several mRNAs mediated by an internal
      ribosome entry site. In this study, we report the crystal structure of the C
      terminal region of DAP5/p97 extending between amino acids 730 and 897. This
      structure consists of four HEAT-Repeats and is homologous to the C-terminal
      domain of eIF4GI, eIF5, and eIF2Bepsilon. Unlike the other proteins, DAP5/p97
      lacks electron density in the loop connecting alpha3 and alpha4, which harbors
      the caspase cleavage site. Moreover, we observe fewer interactions between these
      two helices. Thus, previous mapping of this site by mutation analysis is
      confirmed here by the resolved structure of the DAP5/p97 C-terminus. In addition,
      we identified the position of two conserved aromatic and acidic boxes in the
      structure of the DAP5/p97 C-terminus. The acidic residues in the two aromatic and
      acidic boxes form a continuous negatively charged patch, which is suggested to
      make specific interactions with other proteins such as eIF2beta. The caspase
      cleavage of DAP5/p97 removes the subdomain carrying acidic residues in the AA-box
      motif, which may result in exposure of a hydrophobic surface. These intriguing
      structural differences between the two DAP5 isoforms suggest that they have
      different interaction partners and, subsequently, different functions.

PMID- 18722385
TI  - Involvement of altered arginase activity, arginase I expression and NO production
      in accelerated intimal hyperplasia following cigarette smoke extract.
AB  - In the present experiments, we tried to elucidate whether changes in arginase
      activity, protein expression of arginase-I and -II, and NO production are
      involved in accelerating the intimal hyperplasia following administration of
      cigarette smoke extract (CSE). The intimal hyperplasia was caused by removing
      endothelial cells with the aid of balloon embolectomy catheter in the right
      carotid artery of the male rabbit. The left carotid artery underwent sham
      operation and served as control. CSE was prepared by bubbling a stream of
      cigarette smoke into phosphate buffered saline. Rabbits were given subcutaneously
      with CSE once a day for 5 weeks from 1 week before to 4 weeks after the surgery.
      The specimens were assessed histologically and the intima/media ratio (%) was
      evaluated as an index of the intimal hyperplasia. The accelerated intimal
      hyperplasia with CSE was accompanied by the augmentation of the impaired cyclic
      GMP production, enhanced overall arginase activity and up-regulation of arginase
      I. Pearson's correlation coefficient analyses revealed the close relationships
      among the arginase activities in endothelial cells and smooth muscle layer, the
      intimal/media ratio and cyclic GMP production. These results suggest that the
      enhanced arginase activity together with facilitated up-regulation of arginase-I
      with CSE, which was associated with the augmented impairment of NO production,
      shed a new light on the processes associated with accelerating the intimal
      hyperplasia in rabbit carotid arteries following CSE.

PMID- 18722384
TI  - Synonymous mutations and ribosome stalling can lead to altered folding pathways
      and distinct minima.
AB  - How can we understand a case in which a given amino acid sequence folds into
      structurally and functionally distinct molecules? Synonymous single-nucleotide
      polymorphisms in the MDR1 (multidrug resistance 1 or ABCB1) gene involving
      frequent-to-rare codon substitutions lead to identical protein sequences.
      Remarkably, these alternative sequences give a protein product with similar but
      different structures and functions. Here, we propose that long-enough ribosomal
      pause time scales may lead to alternate folding pathways and distinct minima on
      the folding free energy surface. While the conformational and functional
      differences between the native and alternate states may be minor, the MDR1 case
      illustrates that the barriers may nevertheless constitute sufficiently high
      hurdles in physiological time scales, leading to kinetically trapped states with
      altered structures and functions. Different folding pathways leading to
      conformationally similar trapped states may be due to swapping of (fairly
      symmetric) segments. Domain swapping is more likely in the no-pause case in which
      the chain elongates and folds simultaneously; on the other hand, sufficiently
      long pause times between such segments may be expected to lessen the chances of
      swapping events. Here, we review the literature in this light.

PMID- 18722386
TI  - On the spread of epidemics in a closed heterogeneous population.
AB  - Heterogeneity is an important property of any population experiencing a disease.
      Here we apply general methods of the theory of heterogeneous populations to the
      simplest mathematical models in epidemiology. In particular, an SIR (susceptible
      infective-removed) model is formulated and analyzed when susceptibility to or
      infectivity of a particular disease is distributed. It is shown that a
      heterogeneous model can be reduced to a homogeneous model with a nonlinear
      transmission function, which is given in explicit form. The widely used power
      transmission function is deduced from the model with distributed susceptibility
      and infectivity with the initial gamma-distribution of the disease parameters.
      Therefore, a mechanistic derivation of the phenomenological model, which is
      believed to mimic reality with high accuracy, is provided. The equation for the
      final size of an epidemic for an arbitrary initial distribution of susceptibility
      is found. The implications of population heterogeneity are discussed, in
      particular, it is pointed out that usual moment-closure methods can lead to
      erroneous conclusions if applied for the study of the long-term behavior of the
      models.

PMID- 18722387
TI  - Bisexual branching processes in a genetic context: rates of growth for Y-linked
      genes.
AB  - A multitype bisexual branching process is considered to model the behaviour of a
      Y-linked gene with two genotypes in a two-sex population. It is assumed perfect
      fidelity mating with preference of females for the males carrying certain allele
      of the gene. Under these assumptions, we study the rate of growth of each
      genotype on the event of non-extinction. The rate of growth of a genotype may
      depend on whether the other survives or becomes extinct and, in general, both
      genotype frequencies grow at different rates. We also investigate conditions for
      the simultaneous explosion of both genotypes to have positive or zero
      probability.

PMID- 18722388
TI  - The epigenetics of nuclear envelope organization and disease.
AB  - Mammalian chromosomes and some specific genes have non-random positions within
      the nucleus that are tissue-specific and heritable. Work in many organisms has
      shown that genes at the nuclear periphery tend to be inactive and altering their
      partitioning to the interior results in their activation. Proteins of the nuclear
      envelope can recruit chromatin with specific epigenetic marks and can also
      recruit silencing factors that add new epigenetic modifications to chromatin
      sequestered at the periphery. Together these findings indicate that the nuclear
      envelope is a significant epigenetic regulator. The importance of this function
      is emphasized by observations of aberrant distribution of peripheral
      heterochromatin in several human diseases linked to mutations in NE proteins.
      These debilitating inherited diseases range from muscular dystrophies to the
      premature aging progeroid syndromes and the heterochromatin changes are just one
      early clue for understanding the molecular details of how they work. The
      architecture of the nuclear envelope provides a unique environment for epigenetic
      regulation and as such a great deal of research will be required before we can
      ascertain the full range of its contributions to epigenetics.

PMID- 18722389
TI  - Endocannabinoid signaling in microglial cells.
AB  - The endocannabinoid signaling system (eCBSS) is composed of cannabinoid (CB)
      receptors, their endogenous ligands (the endocannabinoids, eCB) and the enzymes
      that produce and inactivate these ligands. Neurons use this signaling system to
      communicate with each other and Delta9-tetrahydrocannabinol (THC), the main
      psychotropic ingredient of Cannabis sativa, induces profound behavioral effects
      by impinging on this communication. Evidence now shows that microglia, the
      macrophages of the brain, also express a functional eCBSS and that activation of
      CB receptors expressed by activated microglia controls their immune-related
      functions. This review summarizes this evidence, discusses how microglia might
      use the eCBSS to communicate with each other and neighboring cells, and argues
      that compounds selectively targeting the eCBSS expressed by microglia constitute
      valuable therapeutics to manage acute and chronic neuroinflammation, without
      inducing the psychotropic effects and underlying addictive properties commonly
      associated with THC.

PMID- 18722392
TI  - Maturation of cortical mismatch responses to occasional pitch change in early
      infancy: effects of presentation rate and magnitude of change.
AB  - Previous studies have reported two types of event-related potential (ERP)
      mismatch responses in infants to infrequent auditory changes: a broad
      discriminative positivity in younger infants and a negativity resembling adult
      mismatch negativity (MMN) in older infants. In the present study, we investigated
      whether the positive discriminative slow wave and the adult-like MMN are
      functionally distinct by examining how they are affected by presentation rate and
      magnitude of change. We measured ERPs from adults, 2-month-olds, and 4-month-olds
      to a repeating piano tone (standard) that occasionally changed in pitch
      (deviant). The pitch changes between standards and deviants were either small
      (1/12 octave) or large (1/2 octave) in magnitude, and the stimulus presentation
      rate was either slow (800 ms SOA) or fast (400 ms SOA). As the presentation rate
      increased, both adults and 4-month-olds showed an MMN response that decreased in
      latency, but was unaffected in amplitude. As the magnitude of the pitch change
      increased, MMN increased in amplitude. On the other hand, only a broad positive
      mismatch response was seen in 2-month-olds. As the presentation rate increased, 2
      month-olds' responses to standard tones decreased in amplitude while their
      responses to deviant tones were unaffected. The magnitude of the pitch change did
      not affect 2-month-olds' responses. These results suggest that pitch is processed
      differently in auditory cortex by 2-month-olds and 4-month-olds, and that a
      cortical change-detection mechanism for pitch discrimination similar to that of
      adults emerges between 2 and 4 months of age.

PMID- 18722390
TI  - A somatic marker theory of addiction.
AB  - Similar to patients with ventromedial prefrontal cortex (VMPC) lesions, substance
      abusers show altered decision-making, characterized by a tendency to choose the
      immediate reward, at the expense of negative future consequences. The somatic
      marker model proposes that decision-making depends on neural substrates that
      regulate homeostasis, emotion and feeling. According to this model, there should
      be a link between alterations in processing emotions in substance abusers, and
      their impairments in decision-making. Growing evidence from neuroscientific
      studies indicate that core aspects of addiction may be explained in terms of
      abnormal emotional/homeostatic guidance of decision-making. Behavioral studies
      have revealed emotional processing and decision-making deficits in substance
      abusers. Neuroimaging studies have shown that altered decision-making in
      addiction is associated with abnormal functioning of a distributed neural network
      critical for the processing of emotional information, and the experience of
      "craving", including the VMPC, the amygdala, the striatum, the anterior cingulate
      cortex, and the insular/somato-sensory cortices, as well as non-specific
      neurotransmitter systems that modulate activities of neural processes involved in
      decision-making. The aim of this paper is to review this growing evidence, and to
      examine the extent to which these studies support a somatic marker theory of
      addiction. We conclude that there are at least two underlying types of
      dysfunction where emotional signals (somatic markers) turn in favor of immediate
      outcomes in addiction: (1) a hyperactivity in the amygdala or impulsive system,
      which exaggerates the rewarding impact of available incentives, and (2)
      hypoactivity in the prefrontal cortex or reflective system, which forecasts the
      long-term consequences of a given action.

PMID- 18722391
TI  - Characterizing intercellular signaling peptides in drug addiction.
AB  - Intercellular signaling peptides (SPs) coordinate the activity of cells and
      influence organism behavior. SPs, a chemically and structurally diverse group of
      compounds responsible for transferring information between neurons, are broadly
      involved in neural plasticity, learning and memory, as well as in drug addiction
      phenomena. Historically, SP discovery and characterization has tracked advances
      in measurement capabilities. Today, a suite of analytical technologies is
      available to investigate individual SPs, as well as entire intercellular
      signaling complements, in samples ranging from individual cells to entire
      organisms. Immunochemistry and in situ hybridization are commonly used for
      following preselected SPs. Discovery-type investigations targeting the
      transcriptome and proteome are accomplished using high-throughput
      characterization technologies such as microarrays and mass spectrometry. By
      integrating directed approaches with discovery approaches, multiplatform studies
      fill critical gaps in our knowledge of drug-induced alterations in intercellular
      signaling. Throughout the past 35 years, the National Institute on Drug Abuse has
      made significant resources available to scientists that study the mechanisms of
      drug addiction. The roles of SPs in the addiction process are highlighted, as are
      the analytical approaches used to detect and characterize them.

PMID- 18722393
TI  - Spontaneous locally restricted EEG alpha activity determines cortical
      excitability in the motor cortex.
AB  - There is growing interest in the functional meaning of rhythmical brain activity.
      For oscillatory brain activity around 10 Hz in the human electroencephalogram
      (EEG) it is discussed whether it is associated with the level of cortical
      excitation. However, it is not clear whether the relation between 10 Hz EEG
      oscillatory activity and cortical excitability is a global, locally very
      unspecific phenomenon or whether focal 10 Hz oscillations in the human brain are
      a highly specific correlate of the cortical excitation level. To determine this
      open question, multichannel EEG was combined with transcranial magnetic
      stimulation (TMS) applied to the primary motor cortex in this study. The present
      data showed that a motor evoked potential was elicited more easily when alpha
      power immediately preceding the magnetic pulse was low, and vice versa.
      Interestingly, this effect was only found for very local EEG alpha activity at
      sites overlying the cortical motor areas to which the TMS pulses were applied.
      This was verified using source localization in 3D space. These data provide
      evidence that the magnitude of motor cortical excitability is determined by the
      amount of topographically specific alpha oscillations in the sensorimotor cortex.

PMID- 18722394
TI  - Heterogeneity of neuroendocrine stress responses in aging rat strains.
AB  - Hyperactivity of the hypothalamo-pituitary-adrenocortical (HPA) axis is linked
      with age-related decrements in cognition and neuronal survival. However, the
      nature and extent of age-related HPA axis deficits vary considerably across and
      indeed, within strains. The current study was designed to assess variance in HPA
      axis function using two rodent models commonly used in aging studies: Fischer 344
      (F344) and F344/Brown-Norway F1 hybrid rats (F344/BN). We examined both basal and
      stress-induced ACTH and corticosterone (CORT) release in two stress contexts
      thought to differ in intensity: novel environment ('mild') and restraint
      ('intense'). Variability of the data was tested with a modification of the Brown
      Forsythe test of homoscedasticity. The results indicated that F344 rats exhibit
      greater peak HPA responses. Furthermore, in most cases variability was increased
      in aged rats relative to young and middle-aged rats of the same strain,
      indicative of the emergence of individual differences in stress responsivity
      amongst older rats. The results suggest that these older rat strains may be
      useful models to further assess individual differences in neuroendocrine aging.

PMID- 18722395
TI  - Electrophysiological correlates of the mesoaccumbens system during male rat
      sexual behaviour.
AB  - It is well known that during the male rat sexual interaction different levels of
      arousal or sexual motivation are involved and that these motivational changes are
      associated with variations in the level of dopamine (DA); however, it is not yet
      known if these changes are associated with a different functionality of the
      nucleus Accumbens (Acc) and Ventral Tegmental Area (VTA), neural structures that
      constitute the DA mesoaccumbens system. Thus, in this study was simultaneously
      recorded the electroencephalogram (EEG) from the VTA and the Acc in order to
      determine if the EEG correlation (r) between these structures shows
      characteristic patterns in relation to four different conditions of sexual
      arousal during the male rat sexual interaction: 1) basal-quiet state (BS); 2)
      exposure to an inaccessible oestrous female (IF); 3) post-intromission (PI); and,
      4) post-ejaculation (PE). Both Acc and VTA showed an increased relative power
      (RP) in the 8-12 Hz band during the PI condition as compared to the other
      periods. The correlation patterns between Acc and VTA were sensitive to different
      arousal levels involved in the male rat sexual interaction: those of the
      interaccumbens and intertegmental r in the 4-7 and 13-21 Hz bands decreased
      specifically in the IF condition, when the male rats experienced an aroused state
      as a result of their exposure to remote stimuli from an inaccessible estrous
      female; whereas the degree of interaccumbens r in the 8-12 Hz band and those of
      Acc-VTA in both hemispheres increased specifically in the PI condition, in which
      the male showed a moderate level of anxiety or alertness provoked by the removal
      of the female. During the non-sexually aroused states, i.e., basal awake-quiet
      state and PE condition, no changes were observed. These results suggest the
      possible participation of the Acc and VTA in both the processing of remote
      stimuli from an oestrous female and in the aroused state that follows the
      intromission response, which would indicate that these connections between Acc
      and VTA are sensitive to the different sexual motivational/arousal states
      involved in the male rat sexual interaction.

PMID- 18722396
TI  - Membrane progestin receptor beta (mPR-beta): a protein related to cumulus
      expansion that is involved in in vitro maturation of pig cumulus-oocyte
      complexes.
AB  - A new group of putative membrane receptors have now been isolated from fish and
      other vertebrates, including human. These proteins are classified into three
      groups known as membrane progestin receptor alpha, beta and gamma (mPR-alpha, 
      beta and -gamma). In the present study we have investigated the role of mPR-beta
      in regulating in vitro maturation (IVM) of pig cumulus-oocyte complexes (COCs).
      RT-PCR and Western blot analysis indicated that COCs contain transcripts and
      proteins for mPR-beta. The levels of both transcripts and proteins increased
      between 0 and 20h IVM, but then decreased between 20 and 44h. The luteinizing
      hormone (LH) and follicle-stimulating hormone (FSH) did not affect mPR-beta
      expression during IVM. Immunofluorescence analysis indicated that the mPR-beta
      was localized in the plasma membrane of cumulus cell. However, in mouse embryonic
      fibroblasts (MEFs), mPR-beta was detected at the endoplasmic reticulum (ER)
      rather than the plasma membrane. Cumulus expansion was impaired significantly
      (P<0.05) when COCs were incubated in maturation medium containing 10% (v/v) anti
      mPR-beta serum during IVM. Bioinformatics analysis predicted that mPR-beta had an
      ER retention motif and an endocytosis internalization motif. These results
      suggest that the mPR-beta is a molecule related to cumulus expansion and it might
      function by regulation of exocytosis. In conclusion, this is the first
      description of the expression patterns and subcellular localization of mPR-beta
      in COCs and might shed light on the function of the protein.

PMID- 18722397
TI  - Retinal parallel pathways: seeing with our inner fish.
AB  - The general organization of the vertebrate retina is highly conserved, in spite
      of structural variations that occur in different animal classes. The retinas of
      cyprinid fish, for example, differ in many aspects from those of primates.
      However, these differences are in the same order of magnitude as those found
      among mammalian species. Therefore, it is important to consider whether these
      changes are minor variations on the same theme or whether they lead to
      fundamentally different functions. In this light, we compare the retinal
      organization of teleost fish and mammals as regards parallel processing and
      discuss their many similarities.

PMID- 18722398
TI  - Changes in the functional visual field during search with and without eye
      movements.
AB  - The size of the functional visual field (FVF) is dynamic, changing with the
      context and attentive demand that each fixation brings as we move our eyes and
      head to explore the visual scene. Using performance measures of the FVF we show
      that during search conditions with eye movements, the FVF is small compared to
      the size of the FVF measured during search without eye movements. In all cases
      the size of the FVF is constrained by the density of distracting items. During
      search without eye movements the FVF expands with time; subjects have
      idiosyncratic spatial biases suggesting covert shifts of attention. For search
      within the constraints imposed by item density, the rate of item inspection is
      the same across all search conditions. Array set size effects are not apparent
      once stimulus density is taken into account, a result that is consistent with a
      spatial constraint for the FVF based on the cortical separation hypothesis.

PMID- 18722399
TI  - Time course of the ethanol-like discriminative stimulus effects of abused
      inhalants in mice.
AB  - Abused solvents have effects similar to those of abused depressant drugs. This
      experiment evaluated the time course of the discriminative stimulus effects of
      toluene and 1,1,1-trichloroethane (TRI). Mice were trained to discriminate
      between i.p. injections of ethanol (EtOH; 1.25 g/kg) and saline in a two-lever
      operant task in which responding was under the control of a fixed-ratio 20
      schedule. After 20-min inhalation exposures to toluene (500-6000 ppm) or TRI
      (1000-12,000 ppm), stimulus generalization was examined at 0, 5, 10, 20, and 40
      min post-exposure. Ethanol doses>or=0.25 g/kg produced increases in EtOH-lever
      responding with full substitution occurring immediately after testing for doses
      between 1.25 and 2.5 g/kg. Toluene and TRI produced increased EtOH-lever
      responding at 0-10 min post-exposure with some EtOH-lever responding occurring up
      to 20-min post-exposure. Response rates were not decreased for any concentration
      of toluene or TRI immediately following inhalant exposure but several
      concentrations elevated rates from 5 to 40 min post-exposure. These results
      confirm and extend previous studies and show these solvents produce similar
      effects in EtOH-lever responding but with potency differences. The time-dependent
      differences in EtOH-lever responding suggest that as solvents are cleared from
      the body, the EtOH-like subjective effects also fade.

PMID- 18722400
TI  - Screen-viewing and the home TV environment: the European Youth Heart Study.
AB  - OBJECTIVE: Examine if home environmental factors are associated with screen
      viewing. METHODS: Data are for 2670, 3rd and 9th grade participants in Denmark,
      Portugal, Estonia and Norway collected between 1997 and 2000. Outcomes were
      spending >2 h after-school watching television (TV) and >1 h per day playing
      computer games. Child Autonomy and the home TV Environment were exposures.
      RESULTS: Each unit increase in Child Autonomy was associated with 9% increase in
      risk of watching more than 2 h of TV per day after school and a 19% increase in
      risk of spending more than an hour per day playing computer games. TV Environment
      was associated with a 31% per unit increase in risk of watching >2 h of TV after
      school and 11% increase in risk of spending >1 h playing computer games.
      CONCLUSIONS: A family environment in which after-school TV viewing is part of the
      home culture and homes where children have more autonomy over their own behavior
      are associated with an increased risk of watching >2 h of TV per day after school
      and spending more >1 h per day playing computer games. The home screen-viewing
      environment and Child Autonomy may be malleable targets for changing screen
      viewing.

PMID- 18722401
TI  - Synthesis of calixarene-based cavitands and nanotubes by click chemistry.
AB  - The synthesis of a variety of calixarene-based cavitands (capped and functional
      calixarenes) and calix nanotubes is easily performed in good to high yields using
      "click chemistry" methodology through the Cu(I)-catalyzed ligation of adequate
      bis-alkyne and bis-azide derivatives.

PMID- 18722402
TI  - Selective generation of lithiated benzonitriles: the importance of reaction
      conditions.
AB  - Lithiated benzonitriles can be generated in high yields from reactions of
      bromobenzonitriles with n-BuLi in THF under standard cryogenic conditions (ca. 
      70 degrees C) provided the reverse addition mode is employed. The resultant
      aryllithiums are fairly stable at temperatures up to -60 degrees C. The formation
      of lithiated benzonitriles via Br/Li exchange under normal addition mode
      conditions is plagued by deprotonation and extensive CN-addition reactions. The
      generation of related aryllithiums from disilylated bromobenzonitriles is
      comparatively less sensitive to reaction conditions.

PMID- 18722403
TI  - THAL, a sterically unhindered linker for the solid-phase synthesis of acid
      sensitive protected peptide acids.
AB  - The 5-(4-hydroxyphenyl)-3,4-ethylenedioxythienyl alcohol (THAL, Thiophene Acid
      Labile) is described as a new linker for the solid-phase synthesis of peptide
      carboxylic acids. It is based on the electron-rich 3,4-ethylenedioxythenyl
      (EDOTn) moiety and allows the obtention of free and tert-butyl-protected peptides
      by cleavage with 90% and 0.5% TFA, respectively. This very high acid lability
      makes it useful for the synthesis of sensitive peptides. Free and tert-butyl
      protected Leu-enkephalins have been synthesized as models to demonstrate the
      utility of the linker.

PMID- 18722404
TI  - Olefin ring closing metathesis and hydrosilylation reaction in aqueous medium by
      Grubbs second generation ruthenium catalyst.
AB  - The Grubbs second generation ruthenium catalyst was shown to catalyze various
      olefin ring closing metathesis and hydrosilylation reactions in aqueous medium.
      Reactions proceeded in pure water without any additives or cosolvents, in a short
      period of time. We found that inhomogeneity of the reaction mixture does not
      prevent high conversion (70-95%) of the products in both reactions.

PMID- 18722405
TI  - Control of the regioselectivity for new fluorinated amphiphilic cyclodextrins:
      synthesis of di- and tetra(6-deoxy-6-alkylthio)- and 6-(perfluoroalkypropanethio)
      alpha-cyclodextrin derivatives.
AB  - Twelve new di- and tetraderivatized alpha-cyclodextrin molecules having either
      alkylthio and perfluoroalkylpropanethio functions at the primary face have been
      synthesized by using the procedure of Sinay for di-O-debenzylation of
      perbenzylated alpha-cyclodextrins. A new strategy of protection/deprotection has
      been developed for introducing the lipophilic chains. The coupling reaction
      involves the reaction between the appropriate alpha-cyclodextin derivative,
      regioselectively modified at C-6 positions by a good leaving group (O-mesityl for
      disubstituted or iodine for tetrasubstituted derivatives), with the thioalkyl or
      the thioperfluoroakylpropane chains. These nucleophilic reagents are obtained
      from the in situ basic hydrolysis of the alkylisothiouronium bromides or
      perfluoalkylropropane and the isothiouronium iodides. These multistep reactions
      give the desired amphiphilic alpha-cyclodextrins in good overall yields of 33% to
      58%.

PMID- 18722406
TI  - Mechanisms of acid decomposition of dithiocarbamates. 5. Piperidyl
      dithiocarbamate and analogues.
AB  - In this work, the acid cleavage at 25 degrees C in 20% v/v aqueous ethanol of a
      series of analogues of piperidine dithiocarbamate X(C2H4)2NCS2(-) (X = CH2,
      CHCH3, NH, NCH3, S, O) was studied. The pH-rate profiles were obtained in the
      range of H(o)-5 and pH 5. They all presented a dumbell shaped curve with a
      plateau from which the pH-independent first-order rate constant k(o) (or the
      specific acid catalysis k(H)) was calculated, in addition to the acid
      dissociation constant of the free (pKa) and conjugate acid (pK(+)) species of the
      DTC. LFERs of the kinetically determined pKa and pK(+) versus pKN (pKa of parent
      amine) were used to characterize the reactive species and the structure of the
      transition state of the rate-determining step. For X = CH2, CH3CH the values of
      k(H) agree with those of alkDTCs in the strong base region of the Bronsted plot
      of log k(H) versus pKN where the transition state is close to a zwitterion formed
      by intramolecular water-catalyzed S-to-N proton transfer of the dithiocarbamic
      acid. However, when X = NH, CH 3N, O, S, the reactive species is the DTC anion,
      which is as reactive as an arylDTC, and similarly, the pK(+) values correspond to
      a parent amine that is about 3-4 pK units more basic. The solvent isotope effect
      indicated that the acid decomposition of these dithiocarbamate anions is
      specifically catalyzed by a Hydron anchimerically assisted by the heteroatom
      through a boat conformation.

PMID- 18722407
TI  - Highly enantioselective sequential hydrogenation of ethyl 2-oxo-4-arylbut-3
      enoate to ethyl 2-hydroxy-4-arylbutyrate.
AB  - The hydrogenation of (E)-ethyl 2-oxo-4-arylbut-3-enoate with [NH2Me2](+)[{RuCl
      [(S)-SunPhos]}2(mu-Cl3)] gave ethyl 2-hydroxy-4-arylbutyrate with 94-96% ee.
      Further investigation has proved that the hydrogenation proceeded via a
      sequential hydrogenation of CO and CC bonds, which is sensitive to the reaction
      temperature. Hydrolysis of ethyl 2-hydroxy-4-phenylbutyrate (ee 93%) provided the
      2-hydroxy-4-phenylbutyric acid with 81% yield at 99% ee after a single
      recrystallization from 1,2-dichloroethylene.

PMID- 18722409
TI  - A new synthetic approach to N-arylquinolino[2,3,4-at]porphyrins from beta
      arylaminoporphyrins.
AB  - A new reaction leading to porphyrins bearing fused rings is described. Novel N
      arylquinolino[2,3,4-at]porphyrins 2 were obtained by thermal oxidative
      cyclization of beta-arylaminoporphyrins 1. The starting beta-arylaminoporphyrins
      were prepared by two routes: (i) nucleophilic displacement of the nitro group
      from 2-nitro-5,10,15,20-tetraphenylporphyrin by anilines and (ii) palladium
      catalyzed amination of bromobenzene derivatives with (2-amino-5,10,15,20
      tetraphenylporphyrinato)nickel(II). The N-arylquinolino[2,3,4-at]porphyrins show
      interesting UV-vis spectra with strong absorption bands in the red region.

PMID- 18722408
TI  - Palladium-catalyzed reactions of arylindium reagents prepared directly from aryl
      iodides and indium metal.
AB  - Treatment of aryl iodides with indium metal in the presence of lithium chloride
      leads to the formation of an organoindium reagent capable of participating in
      cross-coupling reactions under transition-metal catalysis. Combination with aryl
      halides in the presence of 5 mol % Cl2Pd(dppf) furnishes biaryl compounds in good
      yields; similarly, reaction with acyl halides or allylic acetates/carbonates in
      the presence of 5-10 mol % palladium catalyst leads to arylketones and allylic
      substitution products, respectively, in moderate yields. The reactions are
      tolerant of the presence of protic solvents, and approximately 85% of the indium
      metal employed can be recovered by reduction of the residual indium salts with
      zinc(0).

PMID- 18722410
TI  - Diels-Alder approach to biaryls: elucidation of competing tandem [2+2]
      cycloaddition/[1,3] sigmatropic shift pathway.
AB  - Reaction of 2-halo-6-nitrophenylacetylene with an electron deficient diene gives
      rise to a [4+2] cycloaddition/cycloreversion biaryl product and a
      bicyclo[4.2.0]octadiene resulting from a competing [2+2] cycloaddition pathway.
      The cyclobutene can be opened to give a mixture of cyclooctatriene and biaryl in
      varying amounts depending on heat and light exposure. The conversion of the
      cyclobutene into biaryl occurs through a [1,3] sigmatropic carbon shift followed
      by [4+2] cycloextrusion of ethylene gas.

PMID- 18722411
TI  - Generation of nitrene by the photolysis of N-substituted iminodibenzothiophene.
AB  - To evaluate the ability of dibenzothiophene N-substituted sulfilimines as
      photochemical nitrene sources, their photolyses in the presence of several
      trapping reagents, such as sulfides, olefins, and phosphorus compounds, were
      performed. In the reactions, the corresponding imino-transfer compounds, namely
      sulfilimines, aziridines, and iminophosphoranes, were formed in good yields,
      indicating dibenzothiophene N-tosyl and N-acylsulfilimines have a potent nature
      as nitrogen sources.

PMID- 18722412
TI  - Regiospecifically alpha-13C-labeled porphyrins for studies of ground-state hole
      transfer in multiporphyrin arrays.
AB  - Insight into the electronic communication between the individual constituents of
      multicomponent molecular architectures is essential for the rational design of
      molecular electronic and/or photonic devices. To clock the ground-state
      hole/electron-transfer process in oxidized multiporphyrin architectures, a p
      diphenylethyne-linked zinc porphyrin dyad was prepared wherein one porphyrin
      bears two (13)C atoms and the other porphyrin is unlabeled. The (13)C atoms are
      located at the 1- and 9-positions (alpha-carbons symmetrically disposed to the
      position of linker attachment), which are sites of electron/spin density in the
      a(1u) HOMO of the porphyrin. The (13)C labels were introduced by reaction of
      KS(13)CN with allyl bromide to give the allyl isothiocyanate, which upon Trofimov
      pyrrole synthesis followed by methylation gave 2-(methylthio)pyrrole-2-(13)C.
      Reaction of the latter with paraformaldehyde followed by hydrodesulfurization
      gave dipyrromethane-1,9-(13)C, which upon condensation with a dipyrromethane-1,9
      dicarbinol bearing three pentafluorophenyl groups gave the
      tris(pentafluorophenyl)porphyrin bearing (13)C labels at the 1,9-positions and an
      unsubstituted meso (5-) position. Zinc insertion, bromination at the 5-position,
      and Suzuki coupling with an unlabeled porphyrin bearing a suitably functionalized
      diphenylethyne linker gave the regiospecifically labeled zinc porphyrin dyad.
      Examination of the monocation of the isotopically labeled dyad via electron
      paramagnetic resonance (EPR) spectroscopy (and comparison with the monocations of
      benchmark monomers, where hole transfer cannot occur) showed that the hole
      transfer between porphyrin constituents of the dyad is slow (<10(6) s(-1)) on the
      EPR time scale at room temperature. The slow rate stems from the a(1u) HOMO of
      the electron-deficient porphyrins, which has a node at the site of linker
      connection. In contrast, analogous dyads of electron-rich porphyrins (wherein the
      HOMO is a(2u) and has a lobe at the site of linker connection) studied previously
      exhibit rates of hole transfer that are fast (>5 x 10(7) s(-1)) on the EPR time
      scale at room temperature.

PMID- 18722413
TI  - The charge-transfer properties of the S2 state of fucoxanthin in solution and in
      fucoxanthin chlorophyll-a/c2 protein (FCP) based on stark spectroscopy and
      molecular-orbital theory.
AB  - Fucoxanthin chlorophyll-a/c 2 protein (FCP), the membrane-intrinsic light
      harvesting complex from the diatom Cyclotella meneghiniana, is characterized by
      Stark spectroscopy to obtain a quantitative measure of the excited-state dipolar
      properties of the constituent pigments. The electro-optical properties of the
      carotenoid fucoxanthin (Fx), the primary light harvester in FCP, were determined
      from the Stark spectrum measured in a MeTHF glass (77 K) and compared to the
      results from electronic-structure calculations. On photon absorption by Fx, a 17
      D change in the static dipole moment (|Delta mu|exp), and a somewhat larger
      |Delta mu|exp at the red edge, are measured for the S 0 --> S 2 (1 (1)A g (-)
      like -->1 (1)B u *+-like) transition. The large change in dipole moment indicates
      that Fx undergoes photoinduced charge transfer (CT), and underscores the
      influence of the S 2 state on the polarity-dependent excited-state dynamics of Fx
      that has so far been attributed to, and discussed in terms of, the S 0 and the S
      1/ICT states. MNDO-PSDCI and SACCI-CISD calculations indicate that the 1 (1)B u
      (*+)-like state intrinsically possesses a dipole moment much smaller than the 2
      (1)A g (*-)-like state, suggesting that solvent fields promote the mixing of
      these two states and could account for the large dipole moments measured here for
      the S 0 --> S 2 transition. These CT properties of the 1 (1)B u (*+)-like state
      of Fx are further enhanced in the protein and underpin its photosynthetic
      capabilities for light harvesting and energy transfer (ET). In FCP, the CT
      properties of the Fx's vary according to the energetic position: between 450 and
      500 nm there appear to be two sets of Fx's that exhibit |Delta mu| exp values on
      the order of 5 and 15 D, whereas the red-most Fx's, that are very efficient in ET
      to chlorophyll-a (Chl-a), exhibit strikingly large |Delta mu| exp values on the
      order of 40 D. Such magnitudes of |Delta mu| exp suggest a mechanism that
      enhances Coulombic coupling to promote ET from the S 2 state of Fx to Chl-a.
      These three sets of Fx's, including a fourth red Fx, are identified by fitting
      the Stark spectrum of FCP with the Stark spectrum of Fx in MeTHF. In contrast to
      the Fx's in the protein, the electrostatic properties of the Chl's in FCP are
      comparatively much smaller. Notably, for the Q y band of Chl-a, a |Delta mu| exp
      of 0.92 D and a change in polarizability ( Delta alpha exp) of 20 A (3), indicate
      that the Chl-a's are monomeric in nature and decoupled from each other.

PMID- 18722415
TI  - Theoretical mechanism study of UF6 hydrolysis in the gas phase.
AB  - The mechanism of the gas-phase reaction UF 6 + H 2O --> UOF 4 + 2HF is explored
      using relativistic density functional theory calculations. Initially, H 2O
      coordinates with UF 6 to form a 1:1 complex UF 6.H 2O. Over an activation energy
      barrier of about 19 kcal/mol, H 2O transfers a H atom to a nearby ligand F,
      resulting in UF 5OH + HF. The eliminated HF or another H 2O molecule may form a
      hydrogen bond with UF 5OH. Starting from UF 5OH, the second HF elimination
      results in UOF 4. If UF 5OH is in the isolated form, UF 5OH --> UOF 4 + HF takes
      place over a barrier of 24 kcal/mol. If UF 5OH is hydrogen-bonded with H 2O or
      HF, the conversion barrier is less than 10 kcal/mol. Once formed, the unstable
      UOF 4 tends to associate with additional ligands and hydrogen-bonding donors. The
      calculated binding energies indicate the significance of such interactions, which
      may have profound impact on further HF eliminating reactions. The IR spectra
      features can be used to indicate the formation and interaction type of the
      intermediates and products.

PMID- 18722414
TI  - Biosynthesis of diazepinomicin/ECO-4601, a Micromonospora secondary metabolite
      with a novel ring system.
AB  - The novel microbial metabolite diazepinomicin/ECO-4601 (1) has a unique tricyclic
      dibenzodiazepinone core, which was unprecedented among microbial metabolites.
      Labeled feeding experiments indicated that the carbocyclic ring and the ring
      nitrogen of tryptophan could be incorporated via degradation to the 3
      hydroxyanthranilic acid, forming ring A and the nonamide nitrogen of 1. Genomic
      analysis of the biosynthetic locus indicated that the farnesyl side chain was
      mevalonate derived, the 3-hydroxyanthranilic acid moiety could be formed directly
      from chorismate, and the third ring was constructed via 3-amino-5-hydroxybenzoic
      acid. Successful incorporation of 4,6-D2-3-hydroxyanthranilic acid into ring A of
      1 via feeding experiments supports the genetic analysis and the allocation of the
      locus to this biosynthesis. These studies highlight the enzymatic complexity
      needed to produce this structural type, which is rare in nature.

PMID- 18722416
TI  - MNDO parameters for the prediction of 19F NMR chemical shifts in biologically
      relevant compounds.
AB  - The semiempirical MNDO methodology for qualitative description NMR chemical
      shifts has now been extended with the addition of NMR-specific parameters for the
      fluorine atom. This approach can be employed using semiempirical (AM1/PM3)
      geometries with good accuracy and can be executed at a fraction of the cost of ab
      initio and DFT methods, providing an attractive option for the computational
      studies of (19)F NMR for much larger systems. The data set used in the
      parametrization is large and diverse and specifically geared toward biologically
      relevant compounds. The new parameters are applicable to fluorine atoms involved
      in carbon-fluorine bonds. These parameters yield results comparable to NMR
      calculations performed at the DFT (B3LYP) level using the 6-31++G(d,p) basis set.
      The average R (2) and rms error for this data set is 0.94 and 13.85 ppm,
      respectively, compared to 0.96 and 10.45 ppm when DFT methods are used.

PMID- 18722417
TI  - Investigation of a size-selective single hafnium-encapsulated germanium cage.
AB  - The structures, relative stabilities, and electronic properties of size-selective
      single Hf-encapsulated germanium caged clusters ( n = 9-24) have been
      investigated in detail by density functional method for the first time. The
      dominant growth behavior of the solid nanocluster Hf@Ge n is based on a
      pentagonal prism instead of a hexagonal prism. Analogous to Hf@Si n , the
      encapsulated fullerene-like structure of Hf@Ge n begins to appear at 14, which is
      consistent with the prediction from the reactivity toward water in a recent
      experiment ( J. Phys. Chem. A 2007, 111, 42). Also, similar to Hf@Si n in the
      previous experimental observation ( Chem. Phys. Lett. 2003, 371, 490), the
      binding energy of Hf@Ge n is gradually increased up to the maximum at 16 and
      tends to be decreased subsequently, suggesting that stabilization of large
      germanium cages needs to be realized by doping more Hf atoms. The encapsulated Hf
      will obviously be moved away from the center of the germanium cage if the cluster
      size of Hf@Ge n is larger than 20. According to analysis of the electron density
      of size-selective Hf@Ge n , the covalent character in the germanium framework can
      be affected by the encapsulated position of Hf in the germanium cage. In
      addition, comparison between typical low-lying size-selective Hf@Ge n and Hf@Si n
      ( n = 12, 16 and 20) cages indicates that large-scaled divergence exists in
      stabilities, growth behaviors, electronic properties, and so forth.

PMID- 18722419
TI  - [H2bipy]2[(UO2)6Zn2(PO3OH)4(PO4)4].H2O: an open-framework uranyl zinc phosphate
      templated by diprotonated 4,4'-bipyridyl.
AB  - Under mild hydrothermal conditions, a new organically templated uranyl zinc
      phosphate, [H 2bipy] 2[(UO 2) 6Zn 2(PO 3OH) 4(PO 4) 4].H 2O ( UZnP-2), has been
      synthesized. Structural analysis reveals that UZnP-2 is constructed from UO 7
      pentagonal bipyramids that are linked into edge-sharing dimers that are in turn
      joined together by ZnO 4 and PO 4 tetrahedra to form a three-dimensional network.
      Intersecting channels occur along the a, b, and c axes. These channels house the
      diprotonated 4,4'-bipyridyl cations and water molecules. Ion-exchange experiments
      demonstrate that replacement of the 4,4'-bipyridyl cations by alkali and alkaline
      earth metal cations results in a rearrangement of the framework. Further
      characterization of UZnP-2 is provided by Raman and fluorescence spectroscopy.
      The latter method reveals strong emission from the uranyl moieties with
      characteristic fine structure.

PMID- 18722420
TI  - Exploiting soft and hard X-ray absorption spectroscopy to characterize
      metallodrug/protein interactions: the binding of [trans
      RuCl4(Im)(dimethylsulfoxide)][ImH] (Im = imidazole) to bovine serum albumin.
AB  - The reaction of bovine serum albumin (BSA) with [ trans-RuCl
      4(Im)(dimethylsulfoxide)][ImH] (Im = imidazole) (NAMI-A), an experimental
      ruthenium(III) anticancer drug, and the formation of the respective NAMI-A/BSA
      adduct were investigated by X-ray absorption spectroscopy (XAS) at the sulfur and
      chlorine K-edges and at the ruthenium K- and L 3-edges. Ruthenium K and L 3-edge
      spectra proved unambiguously that the ruthenium center remains in the oxidation
      state +3 after protein binding. Comparative analysis of the chlorine K-edge XAS
      spectra of NAMI-A and NAMI-A/BSA, revealed that the chlorine environment is
      greatly perturbed upon protein binding. Only modest changes were observed in the
      sulfur K-edge spectra that are dominated by several protein sulfur groups.
      Overall, valuable information on the nature of this metallodrug/protein adduct
      and on the mechanism of its formation was gained; XAS spectroscopy turns out to
      be a very suitable method for the characterization of this kind of systems.

PMID- 18722421
TI  - Template synthesis of lanthanide (Pr, Nd, Gd) coordination polymers with 2
      hydroxynicotinic acid exhibiting ferro-/antiferromagnetic interaction.
AB  - Lanthanide coordination polymers were synthesized from Pr(III), Nd(III), and
      Gd(III) salts; 2-hydroxynicotinic acid (Hnica); and MnSO 4.H 2O under
      hydrothermal conditions. In the absence of (CH 3) 3CCOONa, 1D polymers with an
      infinite Ln(III)-O-Ln(III) chain structure, [Pr(Hnica)(H 2O) 2SO 4] n ( 1),
      [Nd(Hnica)(H 2O) 2SO 4] n ( 2), and [Gd(Hnica)(H 2O) 2SO 4] n ( 3), were
      generated. When (CH 3) 3CCOONa was added to the synthetic systems, 2D
      coordination polymers {[Pr 3(Hnica) 6(H 2O) 9].3H 2O.SO 4.NO 3} n ( 4), {[Nd
      3(Hnica) 6(H 2O) 9].3H 2O.SO 4.NO 3} n ( 5), and {[Gd(Hnica) 2(H 2O) 2]ClO 4.H
      2O} n ( 6) were obtained. Complexes 4 and 5 both exhibit Kagome lattice
      structure, while 6 displays a rhombic grid structure. All complexes were
      characterized by elemental analysis, IR spectra, UV-vis spectra, and X-ray single
      crystal diffraction. The variable-temperature magnetic susceptibility studies
      reveal ferromagnetic interactions between gadolinium(III) ions in 3 and 6 and
      antiferromagnetic interactions in 1, 2, 4, and 5.

PMID- 18722422
TI  - Formations of mixed-valence oxovanadiumV,IV citrates and homocitrate with N
      heterocycle chelated ligand.
AB  - Dimeric mixed-valence oxovanadium citrate [V 2O 3(phen) 3(Hcit)].5H 2O ( 1) (H
      4cit = citric acid, phen = 1,10-phenanthroline) was isolated from a weak acidic
      medium. It could be converted quantitatively into a tetrameric oxovanadium
      citrate adduct of 1,10-phenanthroline [V 2O 3(phen) 3(Hcit) 2(phen) 3O 3V 2].12H
      2O ( 2). This was supported by the trace of infrared spectra and X-ray
      diffraction patterns. The two compounds feature a bidentate citrate group that
      chelates only to one vanadium center through their negatively charged alpha
      alkoxy and alpha-carboxy oxygen atoms, while the other beta-carboxy and beta
      carboxylic acid groups are free to participate in strong intramolecular and
      intermolecular hydrogen bonding [2.45(1) in 1 and 2.487(2) A in 2], respectively.
      This is also the case of homocitrato vanadate(V/IV) [V 2O 3(phen) 3( R, S-H
      2homocit)]Cl.6H 2O ( 3) (H 4homocit = homocitric acid), which features a binding
      mode similar to that found in the R-homocitrato iron molybdenum cofactor of Mo
      nitrogenase. Moreover, the homocitrato vanadate(V) [VO 2(phen) 2] 2[V 2O 4( R,S-H
      2homocit) 2].4H 2O.2C 2H 5OH ( 4) is isolated as a molecular precursor for the
      formation of mixed-valence complex 3. The V-O alpha-alkoxy and V-O alpha-carboxy
      bond distances of homocitrate complexes 3 and 4 are 1.858(4) and 1.968(6) av and
      2.085(4) and 1.937(5) A, respectively. They are shorter than those of homocitrate
      to FeVco (2.15 A). The gamma-carboxy groups of coordinated homocitrato complexes
      3 and 4, and the free homocitrate salt Na 3(Hhomocit).H 2O ( 5), form strong
      hydrogen bonds with the chloride ion and the water molecule [2.982(5) in 3,
      2.562(9) in 4, and 2.763(1) A in 5], respectively.

PMID- 18722423
TI  - Two-dimensional pentacene:3,4,9,10-perylenetetracarboxylic dianhydride
      supramolecular chiral networks on Ag(111).
AB  - Self-assembly of the binary molecular system of pentacene and 3,4,9,10
      perylenetetracarboxylic dianhydride (PTCDA) on Ag(111) has been investigated by
      low-temperature scanning tunneling microscopy, molecular dynamics (MD), and
      density functional theory (DFT) calculations. Well-ordered two-dimensional (2D)
      pentacene:PTCDA supramolecular chiral networks are observed to form on Ag(111).
      The 2D chiral network formation is controlled by the strong interfacial
      interaction between adsorbed molecules and the underlying Ag(111), as revealed by
      MD and DFT calculations. The registry effect locks the adsorbed pentacene and
      PTCDA molecules into specific adsorption sites due to the corrugation of the
      potential energy surface. The 2D supramolecular networks are further constrained
      through the directional CO...H-C multiple intermolecular hydrogen bonding between
      the anhydride groups of PTCDA and the peripheral aromatic hydrogen atoms of the
      neighboring pentacene molecules.

PMID- 18722424
TI  - Highly selective sorption of small unsaturated hydrocarbons by nonporous flexible
      framework with silver ion.
AB  - Ag2[Cr3O(OOCC2H5)6(H2O)3]2[alpha-SiW12O40] [1] is a nonporous flexible ionic
      crystal composed of 2D-layers of polyoxometalates ([alpha-SiW12O40](4-)) and
      macrocations ([Cr3O(OOCC2H5)6(H2O)3](+)) stacking along the b-axis. The silver
      ions are located in the vicinity of the oxygen atoms of the polyoxometalates. The
      sorption amounts of small unsaturated hydrocarbons such as ethylene, propylene, n
      butene, acetylene, and methyl acetylene into 1 are comparable to or larger than
      1.0 mol mol(-1) and large hystereses are observed, while those of paraffins and
      larger unsaturated hydrocarbons are smaller than the adsorption on the external
      surface (<0.2 mol mol(-1)). Fine crystals of 1 exhibit ethylene/ethane and
      propylene/propane sorption ratios over 100 at 298 K and 100 kPa, and the values
      are larger by 1 order of magnitude among those reported. The results of sorption
      kinetics, in situ IR spectroscopy, single crystal X-ray crystallography, and in
      situ powder XRD studies show that small unsaturated hydrocarbons penetrate into
      the solid bulk of 1 through the pi-complexation with Ag(+). The sorption property
      of 1 is successfully applied to the collection of ethylene from the gas mixture
      of ethane and ethylene.

PMID- 18722425
TI  - Combinatorial discovery of full-color-tunable emissive fluorescent probes using a
      single core skeleton, 1,2-dihydropyrrolo[3,4-beta]indolizin-3-one.
AB  - We developed a novel fluorescent core skeleton, 1,2-dihydropyrrolo[3,4
      beta]indolizin-3-one, by complexity-generating one-pot reactions through 1,3
      dipolar cyclization followed by oxidative aromatization. This fluorescent core
      skeleton can accommodate various wavelengths of emission maxima by changing the
      electronic properties of substituents, which was postulated by computational
      studies. The full-color-tunable emission maxima were achieved with a single core
      skeleton by changing the substituents using the combinatorial approach. These
      novel fluorophores have excellent photophysical and photochemical properties:
      moderate to excellent quantum yields, resistance to the photobleaching, pH
      independent fluorescence, large Stokes shifts, druglike lipophilicity for
      membrane permeability, etc. Further, we successfully demonstrated the
      bioapplication of fluorophores B1 and B5 in the immunofluorescence for
      visualizing cellular compartments of HeLa cells.

PMID- 18722426
TI  - Reaction chemistry and ligand exchange at cadmium-selenide nanocrystal surfaces.
AB  - The surface chemistry of cadmium selenide nanocrystals, prepared from tri-n
      octylphosphine selenide and cadmium octadecylphosphonate in tri-n-octylphosphine
      oxide, was studied with 1H and {1H}31P NMR spectroscopy as well as ESI-MS and
      XPS. The identity of the surface ligands was inferred from reaction of
      nanocrystals with Me3Si-X (X = -S-SiMe3, -Se-SiMe3, -Cl and -S-(CH2CH2O)4OCH3))
      and unambiguous assignment of the organic byproducts, O,O'
      bis(trimethylsilyl)octadecylphosphonic acid ester and O,O'
      bis(trimethylsilyl)ocatdecylphosphonic acid anhydride ester. Nanocrystals
      isolated from these reactions have undergone exchange of the octadecylphosphonate
      ligands for -X as was shown by 1H NMR (X = -S-(CH2CH2O)4OCH3) and XPS (X = -Cl).
      Addition of free thiols to as prepared nanocrystals results in binding of the
      thiol to the particle surface and quenching of the nanocrystal fluorescence.
      Isolation of the thiol-ligated nanocrystals shows this chemisorption proceeds
      without displacement of the octadecylphosphonate ligands, suggesting the presence
      of unoccupied Lewis-acidic sites on the particle surface. In the presence of
      added triethylamine, however, the octadecylphosphonate ligands are readily
      displaced from the particle surface as was shown with 1H and {1H}31P NMR. These
      results, in conjunction with previous literature reports, indicate that as
      prepared nanocrystal surfaces are terminated by X-type binding of
      octadecylphosphonate moieties to a layer of excess cadmium ions.

PMID- 18722427
TI  - New aldehyde tag sequences identified by screening formylglycine generating
      enzymes in vitro and in vivo.
AB  - Formylglycine generating enzyme (FGE) performs a critical posttranslational
      modification of type I sulfatases, converting cysteine within the motif CxPxR to
      the aldehyde-bearing residue formylglycine (FGly). This concise motif can be
      installed within heterologous proteins as a genetically encoded "aldehyde tag"
      for site-specific labeling with aminooxy- or hydrazide-functionalized probes. In
      this report, we screened FGEs from M. tuberculosis and S. coelicolor against
      synthetic peptide libraries and identified new substrate sequences that diverge
      from the canonical motif. We found that E. coli's FGE-like activity is similarly
      promiscuous, enabling the use of novel aldehyde tag sequences for in vivo
      modification of recombinant proteins.

PMID- 18722428
TI  - Structural studies of heparan sulfate hexasaccharides: new insights into
      iduronate conformational behavior.
AB  - There is a growing opinion that the conformational dynamics within HS chains is
      critical to their observed biological activities. Investigations into HS
      conformational dynamics are problematic, given the structural complexity and
      heterogeneity of HS chains. However, this goal will be more obtainable once we
      understand the important roles HS sequence/sulfation patterns play in determining
      the conformational dynamics of iduronate units. This is the first study to
      compare isomers of N-sulfated oligosaccharides, with respect to the
      conformational versatility of their internal iduronates. Characterization by NMR
      spectroscopy of two HS oligosaccharides derived from porcine mucosal HS enabled
      the measurement of iduronate coupling constants, while under the influence of
      different flanking saccharide sequences. By fitting our coupling constant data to
      a new set of theoretical coupling constants, calculated using explicit water
      molecular dynamic simulations, we are able to offer new insights into the role
      sequence/sulfation patterns play in influencing iduronate conformational
      behavior. Fitting of experimental data, using our new theoretically derived
      coupling constants, suggests that replacement of the N-sulfate group to the
      reducing side of IdoUA by an N-acetyl group has little effect on the balance of
      IdoUA conformational equilibrium. Fitting of coupling constants for sequences
      GlcNS-IdoUA(2S)-GlcNS and GlcNS(6S)-IdoUA(2S)-GlcNS suggests that the flanking 6
      O-sulfate group alters the balance of the IdoUA(2S) equilibrium more toward the
      (2)S0 conformation. There is also the suggestion that a cooperative effect may
      exist for N- and 6-O sulfation. These observations could be the key to
      understanding the important regulatory function attributed to 6-O-sulfation
      within HS chains.

PMID- 18722429
TI  - Photochemistry of adsorbed nitrate.
AB  - In the atmosphere, gas-phase nitrogen oxides including nitric acid react with
      particle surfaces (e.g., mineral dust and sea salt aerosol) to yield adsorbed
      nitrate, yet little is known about the photochemistry of nitrate on the surface
      of these particles. In this study, nitrate adsorbed on alumina surfaces, a
      surrogate for mineral dust aerosol, is irradiated with broadband light (lambda >
      300 nm) in the absence and presence of coadsorbed water, at <1% and 45 +/- 2%
      relative humidity (%RH), respectively, and molecular oxygen. Upon irradiation,
      the nitrate ion readily undergoes photolysis to yield nitrogen-containing gas
      phase products, NO2, NO, and N2O. Although NO2, NO, and N2O form under the
      different conditions investigated, both coadsorbed water and molecular oxygen
      change the gas-phase product distribution, with NO being the major product under
      dry and humid conditions in the absence of molecular oxygen and NO2 the major
      product in the presence of molecular oxygen. To the best of our knowledge, this
      is the first study to investigate the role of solvation by coadsorbed water in
      the photochemistry of adsorbates at solid interfaces and the roles that molecular
      oxygen, adsorbed water, and relative humidity may have in photochemical processes
      on aerosol surfaces that have the potential to alter the chemical balance of the
      atmosphere.

PMID- 18722430
TI  - Structure and properties of small molecule-polymer blend semiconductors for
      organic thin film transistors.
AB  - A comprehensive structural and electrical characterization of solution-processed
      blend films of 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-pentacene)
      semiconductor and poly(alpha-methylstyrene) (PalphaMS) insulator was performed to
      understand and optimize the blend semiconductor films, which are very attractive
      as the active layer in solution-processed organic thin-film transistors (OTFTs).
      Our study, based on careful measurements of specular neutron reflectivity and
      grazing-incidence X-ray diffraction, showed that the blends with a low molecular
      mass PalphaMS exhibited a strong segregation of TIPS-pentacene only at the air
      interface, but surprisingly the blends with a high molecular-mass PalphaMS showed
      a strong segregation of TIPS-pentacene at both air and bottom substrate
      interfaces with high crystallinity and desired orientation. This finding led to
      the preparation of a TIPS-pentacene/PalphaMS blend active layer with superior
      performance characteristics (field-effect mobility, on/off ratio, and threshold
      voltage) over those of neat TIPS-pentacene, as well as the solution
      processability of technologically attractive bottom-gate/bottom-contact OTFT
      devices.

PMID- 18722431
TI  - Nitrosobenzene-mediated C-C bond cleavage reactions and spectral observation of
      an oxazetidin-4-one ring system.
AB  - While bond formation processes have traditionally garnered the attention of the
      chemical community, methods facilitating bond breaking remain relatively
      undeveloped. We report a novel, transition-metal-free oxidative C-C bond cleavage
      process for a broad range of ester and dicarbonyl compounds involving carbanion
      addition to nitrosobenzene. ReactIR experiments on the nitrosobenzene-mediated
      oxidative decarboxylation of esters indicate the reaction proceeds via
      fragmentation of a previously unobserved oxazetidin-4-one heterocycle,
      characterized by an intense IR stretching frequency at 1846 cm-1. These
      mechanistic studies have allowed further expansion of this protocol to ketone
      cleavage reactions of a diverse array of beta-ketoester and 1,3-diketone
      substrates. The conceptual and mechanistic insights offered by this study are
      likely to provide a platform for further development of bond-breaking
      methodologies.

PMID- 18722432
TI  - Direct site-selective covalent protein immobilization catalyzed by a
      phosphopantetheinyl transferase.
AB  - Immobilization of proteins onto solid supports is important in the preparation of
      functional protein microarrays and in the development of bead-based bioassays,
      biosensors, and industrial biocatalysts. In order to generate the stable,
      functional, and homogeneous materials required for these applications, attention
      has focused on methods that enable the efficient and site-specific covalent
      immobilization of recombinant proteins onto a wide range of platforms. To this
      end, the phosphopantetheinyl transferase Sfp was employed to catalyze the direct
      immobilization of recombinant proteins bearing the small, genetically encoded
      ybbR tag onto surfaces functionalized with CoA. Using mass spectrometry, it was
      shown that the Sfp catalyzes immobilization of a model acyl carrier protein (ACP)
      onto CoA-derivatized PEGA resin beads through specific covalent bond formation.
      Luciferase (Luc) and glutathione-S-transferase (GST) ybbR-fusion proteins were
      similarly immobilized onto PEGA resin retaining high levels of enzyme activity.
      This strategy was also successfully applied for the immobilization of the ACP, as
      well as ybbR-Luc, -GST, and -thioredoxin fusion proteins, on hydrogel microarray
      slides. Overall, the Sfp-catalyzed surface ligation is mild, quantitative, and
      rapid, occurring in a single step without prior chemical modification of the
      target protein. Immobilization of the target proteins directly from a cell lysate
      mixture was also demonstrated.

PMID- 18722433
TI  - Synthesis of 1-oxadecalins from anisole promoted by tungsten.
AB  - The complex TpW(NO)(PMe3)(eta(2)-anisole) is combined with acrolein or methyl
      vinyl ketone and various nucleophiles to generate novel chromen complexes. These
      complexes may be further elaborated by protonation and nucleophilic addition to
      generate chroman analogues with increased saturation and stereocenters. Treatment
      with various oxidants effects the decomplexation of the chromen.

PMID- 18722434
TI  - Catalytic enantioselective aldol additions of alpha-isothiocyanato imides to
      aldehydes.
AB  - Highly enantioselective organocatalytic aldol additions of alpha-isothiocyanato
      imides to aldehydes are reported. These reactions provide convenient access to
      enantiomerically enriched and protected beta-hydroxy-alpha-amino acids with
      catalyst loadings as low as 1 mol%.

PMID- 18722435
TI  - Color kinetic nanoparticles.
AB  - Eu3+ doped LaF3 nanoparticles functionalized with a 3-4 formylphenyl benzoic acid
      ligand were synthesized. Excitation energy-dependent energy transfer from the
      ligand to Eu3+ yields color tunability from the red to greenish-blue as a
      function of excitation wavelengths. This synthetic approach provides large shifts
      in the resultant chromaticity with an excitation wavelength including the
      generation of white light.

PMID- 18722436
TI  - Chain-terminus triggered chiral memory in an optically inactive 3(10)-helical
      peptide.
AB  - A new optically inactive 3(10)-helical peptide with a side-chain cross-linking
      was found to exhibit chiral memory stored in the peptide backbone, whose
      chirality was induced by a noncovalent interaction of a chiral molecule at the N
      terminal end of the peptide.

PMID- 18722437
TI  - Rhodium-catalyzed substitution reaction of aryl fluorides with disulfides: p
      orientation in the polyarylthiolation of polyfluorobenzenes.
AB  - In the presence of a catalytic amount of RhH(PPh3)4 and 1,2
      bis(diphenylphosphino)benzene, an aromatic fluoride, an organic disulfide (0.5
      equiv), and triphenylphosphine (0.5 equiv) reacted in refluxing chlorobenzene to
      give an aryl sulfide in high yield. Since triphenylphosphine trapped fluoride
      atoms forming phosphine difluoride, both organothio groups of the disulfide
      reacted effectively, and the fluoride substituent reacted more readily than the
      chloride and bromide. The reaction of hexafluorobenzene and a diaryl disulfide
      gave 1,4-diarylthio-2,3,5,6-tetrafluorobenzene, 1,2,4,5-tetraarylthio-3,6
      difluorobenzene, and hexaarylthiobenzene in a stepwise manner; pentafluorobenzene
      gave 1-arylthio-2,3,5,6-tetrafluorobenzene; 1,2,3,4-tetrafluorobenzene gave 1,2
      diarylthio-3,6-difluorobenzene; and 1,2,4,5-tetrafluorobenzene gave 1,4
      diarylthio-2-5-difluorobenzene. The polyarylthiolation reaction of
      polyfluorobenzenes exhibited a strong tendency to form 1,4-difluorobenzenes.

PMID- 18722438
TI  - A conclusive mechanism of the photoinduced reaction cascade in blue light using
      flavin photoreceptors.
AB  - On the basis of extensive first-principle calculations within the framework of
      quantum mechanics/molecular mechanics (QM/MM), a conclusive mechanism for the
      formation of the signaling state of blue light using flavin (BLUF) domain
      proteins is proposed which is compatible with the experimental data presently
      available. Time-dependent density functional, as well as advanced coupled cluster
      response theory was employed for the QM part in order to describe the relevant
      excited states. One of the key residues involved in the mechanism is the
      glutamine adjacent to the flavin chromophore. The reaction cascade, triggered by
      the initial photoexcitation of the flavin chromophore, involves isomerization of
      this residue but no rotation as assumed previously. The fact that only the
      environment, but not the flavin chromophore by itself, is chemically transformed
      along the individual steps of the mechanism is unique for biological
      photoreceptors. The final isomer of the glutamine tautomer, i.e., the imidic
      acid, is further stabilized by the interchange of a methionine residue in the
      binding pocket with a tryptophan residue. The flip of these two residues might be
      the trigger for the large conformational change of this protein which is
      consequently transmitted as the signal to the biological environment.

PMID- 18722439
TI  - Large two-photon absorption cross sections of hemiporphyrazines in the excited
      state: the multiphoton absorption process of hemiporphyrazines with different
      central metals.
AB  - A series of five hemiporphyrazines (Hps) with different coordinating central
      atoms (H2, GeCl2, InCl, Pt, Pb), and the acyclic derivative 1,3-bis-(6'-amino-4'
      butoxy-2'-pyridylimino)-1,3-dihydroisoindoline have been synthesized and their
      multiphoton absorption properties examined at the second harmonic frequency of
      the Nd:YAG laser in the nanosecond time regime. Metal-free and platinum Hps
      display saturation of optical transmittance within incident fluence values of 6 J
      cm(-2). Comparison with other similar molecular structures like phthalocyanines
      and related molecules shows that Hps are strong nonlinear absorbers. The
      experimental curves of nonlinear transmission at 532 nm have been fitted by means
      of a three-level model with the occurrence of simultaneous two-photon absorption
      from an excited state. In the sole case of the InCl complex we found that a five
      level model is needed because of the participation of triplet states. Contrary to
      phthalocyanines, naphthalocyanines, and porphyrins, a heavy central atom does not
      improve the nonlinear absorption properties since a different excited states
      dynamic is involved. The large nonlinear absorption of Hps combined with the very
      small absorption in the visible spectral range makes these molecules a very
      interesting class of molecules for nonlinear optical applications.

PMID- 18722440
TI  - Role of host layer flexibility in DNA guest intercalation revealed by computer
      simulation of layered nanomaterials.
AB  - Layered double hydroxides (LDHs) have been shown to form staged intermediate
      structures in experimental studies of intercalation. However, the mechanism by
      which staged structures are produced remains undetermined. Using molecular
      dynamics simulations, we show that LDHs are flexible enough to deform around
      bulky intercalants such as deoxyribonucleic acid (DNA). The flexibility of
      layered materials has previously been shown to affect the pathway by which
      staging occurs. We explore three possible intermediate structures which may form
      during intercalation of DNA into Mg2Al LDHs and study how the models differ
      energetically. When DNA strands are stacked directly on top of each other, the
      LDH system has a higher potential energy than when they are stacked in a
      staggered or interstratified structure. It is generally thought that staged
      intercalation occurs through a Daumas-Herold or a Rudorff model. We find, on
      average, greater diffusion coefficients for DNA strands in a Daumas-Herold
      configuration compared to a Rudorff model and a stage-1 structure. Our
      simulations provide evidence for the presence of peristaltic modes of motion
      within Daumas-Herold configurations. This is confirmed by spectral analysis of
      the thickness variation of the basal spacing. Peristaltic modes are more
      prominent in the Daumas-Herold structure compared to the Rudorff and stage-1
      structures and support a mechanism by means of which bulky intercalated molecules
      such as DNA rapidly diffuse within an LDH interlayer.

PMID- 18722441
TI  - Total synthesis of haterumalides NA and NC via a chromium-mediated
      macrocyclization.
AB  - The syntheses of haterumalides NA and NC were accomplished via the
      macrocyclization of a chlorovinylidene chromium carbenoid onto a pendant aldehyde
      to generate the C8-C9 bond with the desired stereoisomer as the major product.
      Utilizing the latter chemistry enables access to both C9 hydroxylated
      (haterumalides NC and ND) and C9 deoxygenated forms (haterumalides NA, NB, and
      NE; via deoxygenation of the C9-hydroxyl).

PMID- 18722442
TI  - Hock cleavage of cholesterol 5alpha-hydroperoxide: an ozone-free pathway to the
      cholesterol ozonolysis products identified in arterial plaque and brain tissue.
AB  - Cholesterol 5alpha-hydroperoxide, the major product of 1O2-oxidation of
      cholesterol, readily undergoes acid-catalyzed (Hock) cleavage of the C5-C6 bond
      to yield the 5,6-secosterol ketoaldehyde and the product of its intramolecular
      aldolization. These cholesterol oxidation products have long been thought to
      arise solely from ozonolysis of cholesterol, prompting the recent suggestion that
      ozone is produced in humans following their identification in arterial and brain
      tissue extracts.

PMID- 18722443
TI  - Catalytic asymmetric addition of alcohols to imines: enantioselective preparation
      of chiral N,O-aminals.
AB  - The enantioselective addition of alcohols to imine electrophiles has been shown
      to proceed in the presence of a catalytic amount of a chiral phosphoric acid
      catalyst. The reaction allows for the formation of the respective chiral N,O
      aminals in excellent yield and enantioselectivity. A total of 11 different
      alcohols and 11 different imines were successfully used as a clear demonstration
      of the reaction generality.

PMID- 18722444
TI  - Multi-electron reduction from alkyl/hydride ligand combinations in U4+ complexes.
AB  - The U4+ mixed alkyl hydride complex (C5Me5)U[mu-C5Me3(CH2)2](mu-H)2U(C5Me5)2, 1,
      which contains a cyclopentadienyl ligand with two metalated methylene
      substituents, can effect four, six, and eight-electron reductions in which the
      combination of the two H1- ligands and the [C5Me3(CH2)2]3- moiety delivers four
      electrons and forms (C5Me5)1-. The reaction is formally equivalent to an alkyl
      hydride reductive elimination, a transformation common with transition metals not
      previously observed with f element compounds. This type of alkyl hydride
      reduction reactivity is also observed with a combination of U4+ alkyl and hydride
      complexes, (C5Me5)2UMe2/[(C5Me5)2UH2]2, which reduces benzene to make
      [(C5Me5)2U]2(C6H6), a U3+ complex formally containing a (C6H6)2- ligand.

PMID- 18722445
TI  - Critical assessment of nucleic acid electrostatics via experimental and
      computational investigation of an unfolded state ensemble.
AB  - Electrostatic forces, acting between helices and modulated by the presence of the
      ion atmosphere, are key determinants in the energetic balance that governs RNA
      folding. Previous studies have employed Poisson-Boltzmann (PB) theory to compute
      the energetic contribution of these forces in RNA folding. However, the complex
      interaction of these electrostatic forces with RNA features such as tertiary
      contact formation, specific ion-binding, and complex interhelical junctions
      present in prior studies precluded a rigorous evaluation of PB theory, especially
      in physiologically important Mg(2+) solutions. To critically assess PB theory, we
      developed a model system that isolates these electrostatic forces. The model
      system, composed of two DNA duplexes tethered by a polyethylene glycol junction,
      is an analog for the unfolded state of canonical helix-junction-helix motifs
      found in virtually all structured RNAs. This model system lacks the complicating
      features that have precluded a critical assessment of PB in prior studies,
      ensuring that interhelical electrostatic forces dominate the behavior of the
      system. The system's simplicity allows PB predictions to be directly compared
      with small-angle X-ray scattering experiments over a range of monovalent and
      divalent ion concentrations. These comparisons indicate that PB is a reasonable
      description of the underlying electrostatic energies for monovalent ions, but
      large deviations are observed for divalent ions. The validation of PB for
      monovalent solutions allows analysis of the change in the conformational ensemble
      of this simple motif as salt concentration is changed. Addition of ions allows
      the motif to sample more compact microstates, increasing its conformational
      entropy. The increase of conformational entropy presents an additional barrier to
      folding by stabilizing the unfolded state. Neglecting this effect will adversely
      impact the accuracy of folding analyses and models.

PMID- 18722446
TI  - Reversible restructuring of aqueous block copolymer assemblies through stimulus
      induced changes in amphiphilicity.
AB  - ABC triblock copolymers with a hydrophilic-thermomorphic-hydrophobic block
      sequence can assemble into distinct structures in water above and below the lower
      critical solution temperature for the thermomorphic block. Characterization of
      aqueous solutions of a representative poly(ethylene oxide)-block-poly(N
      isopropylacrylamide)-block-polyisoprene copolymer by light scattering and
      transmission electron microscopy shows that small spherical micelles are formed
      at low temperatures and that large vesicles are favored at higher temperatures.
      The transformation from micelles to vesicles is reversible but slow, occurring
      over several weeks.

PMID- 18722447
TI  - Structure-property relationships in redox-gated single molecule junctions--a
      comparison of pyrrolo-tetrathiafulvalene and viologen redox groups.
AB  - We demonstrate that the electrical "switching" behavior of single molecules
      connected between two electrode contacts can be controlled by altering their
      structure and electrochemical characteristics. The electrical properties of
      gold|molecule|gold single molecule junctions incorporating HS(CH2)6-X-(CH2)6SH,
      where X = viologen (4,4'-bipyridinium) or pyrrolotetrathiafulvalene, are
      determined using a scanning tunneling microscopy based technique. The switching
      behavior, controlled through a tuneable electrochemical gate, changes from an on
      off response (viologen) to an off-on-off response (pyrrolotetrathiafulvalene) on
      changing the central redox group. In contrast, the electrical properties of
      junctions incorporating redox-inactive HS(CH2)6-1,4-C6H4-(CH2)6SH do not alter
      significantly as a function of applied potential.

PMID- 18722448
TI  - Mechanistically inspired design of Fe(III)-TAML peroxide-activating catalysts.
AB  - Recent broad-ranging mechanistic studies of FeIII-TAML peroxide activators enable
      a strategy for designing catalysts with improved (i) hydrolytic and (ii)
      operational stabilities, (iii) faster activation of H2O2 and other peroxides, and
      (iv) a pH of highest activity closer to 7. Combining all items of insight leads
      to [Fe{1-NO2C6H3-3,4-(NCOCMe2NCO)2CF2}(OH2)]- (1a) which exhibits the most
      desirable technical performance in its class.

PMID- 18722449
TI  - Proline as Lewis base catalyst: diastereoselective synthesis of isoxazoline-N
      oxide through [3 + 2] cycloaddition.
AB  - A catalytic cascade synthesis of isoxazoline-N-oxide was developed through
      proline-catalyzed nitroalkene activation. A large substrate scope was obtained
      with good to excellent yields. Mechanistic studies revealed intramolecular
      cyclization as the rate-determining step, giving only trans isomers in all cases.

PMID- 18722450
TI  - Design of a fluorescent dye for indicator displacement from cucurbiturils: a
      macrocycle-responsive fluorescent switch operating through a pKa shift.
AB  - The derivatization of 3-amino-9-ethylcarbazole with a diamino-alkyl anchor
      affords a fluorescent dye suitable for indicator displacement from cucurbituril
      macrocycles. The novel compound 1 shows, due to a complexation-induced pKa shift,
      a large and predictable dual fluorescence response (100-fold increase at 375 nm
      and 9-fold decrease at 458 nm) upon supramolecular encapsulation and a strong
      affinity for cation-receptor macrocycles, in particular cucurbit[6]uril (CB6). A
      direct application is presented by monitoring the enzymatic activity of lysine
      decarboxylase.

PMID- 18722451
TI  - Preference of beta-lactam formation in Cu(I)-catalyzed intramolecular coupling of
      amides with vinyl bromides.
AB  - A general and highly efficient synthesis of 4-alkylidene-2-azetidinones was
      achieved by the Cu(I)-catalyzed intramolecular C-N coupling of amides with vinyl
      bromides. This 4-exo ring closure was found to be fundamentally preferred over
      other modes (5-exo, 6-exo, and 6-endo) of cyclization under copper catalysis.
      Tandem C-N bond formation was then successfully developed to allow the convenient
      generation of medium-sized lactams.

PMID- 18722452
TI  - Stereoselective oxidative rearrangement of 2-aryl tryptamine derivatives.
AB  - The oxidation of 2-aryl tryptamines followed by a stereoselective rearrangement
      provides a versatile strategy for the synthesis of C3-quaternary oxindoles
      bearing a C3-aryl group. Treatment of optically active 2-aryl hydroxyindolenines
      with scandium trifluoromethanesulfonate in toluene at 110 degrees C leads to
      complete and stereoselective isomerization to the corresponding C3-aryl oxindoles
      which represent versatile intermediates for the synthesis of C3a-aryl
      hexahydropyrroloindoles.

PMID- 18722453
TI  - Enantioselective synthesis utilizing enantiomorphous organic crystal of achiral
      benzils as a source of chirality in asymmetric autocatalysis.
AB  - Chiral crystals of achiral benzils act as efficient chiral initiators of
      asymmetric autocatalysis to afford highly enantioenriched pyrimidyl alkanols
      whose absolute configurations depend upon the enantiomorph of the crystal used in
      conjunction with asymmetric autocatalysis with amplification of enantiomeric
      excess.

PMID- 18722454
TI  - A general one-step synthesis of beta-nitronitriles.
AB  - The unusual beta-nitronitrile functionality was prepared by a simple one-step
      hydrocyanation of nitroalkenes. These compounds were shown to be precursors to
      monoprotected 1,3-diamines and 1,3-amino alcohols through the in situ formation
      of an alpha-cyano-aldenyde.

PMID- 18722455
TI  - Magnetically separable Pd catalyst for carbonylative Sonogashira coupling
      reactions for the synthesis of alpha,beta-alkynyl ketones.
AB  - A magnetically separable palladium catalyst was simply synthesized through a wet
      impregnation incorporating palladium nanoparticles and superparamagnetic Fe3O4
      nanoparticles in KBH4 solution, which is a highly efficient catalyst for the
      carbonylative Sonogashira coupling reaction of aryl iodides with terminal alkynes
      under phosphine-free conditions. This catalyst is completely magnetically
      recoverable due to the super paramagnetic behavior of Fe3O4 and can be reused
      with sustained selectivity and activity.

PMID- 18722456
TI  - Convergent, regiospecific synthesis of quinolines from o-aminophenylboronates.
AB  - A direct convergent two-component synthesis of quinolines from alpha,beta
      unsaturated ketones and o-aminophenylboronic acid derivatives is reported. The
      reaction is regiocomplementary to the traditional Skraup-Doebner-Von Miller
      synthesis and proceeds under basic rather than strongly acidic conditions.
      Quinolines substituted in the benzenoid ring can be accessed by using substituted
      o-aminophenylboronates prepared by direct palladium-catalyzed borylation of the
      corresponding o-bromoanilines.

PMID- 18722457
TI  - Unusually stable, versatile, and pure arenediazonium tosylates: their
      preparation, structures, and synthetic applicability.
AB  - A new, simple, and effective method for the diazotization of a wide range of
      arylamines has been developed by using a polymer-supported diazotization agent in
      the presence of p-toluenesulfonic acid. Various pure arenediazonium tosylates
      with unusual stabilities can be easily prepared by this method. As a result,
      these salts are useful and versatile substrates for subsequent transformations,
      such as halogenation and Heck-type reactions. The unusual stabilities of
      arenediazonium tosylates are also preliminarily discussed with their X-ray
      structures.

PMID- 18722458
TI  - Platinum- and gold-catalyzed hydrative carbocyclization of oxo diynes for one-pot
      synthesis of benzopyrones and bicyclic spiro ketones.
AB  - We report a one-pot synthesis of benzopyrones and tricyclic spiroketones from
      hydrative carbocyclization of oxodiyne substrates catalyzed by PtCl2 and
      PPh3AuCl/AgOTf, respectively. The distinct carbocyclizations with Pt and Au
      catalysts stem from their altered regioselectivity in the oxo-assisted hydration
      of the neighboring alkyne carbons.

PMID- 18722459
TI  - Highly enantioselective Friedel-Crafts reaction of indoles with 2-enoylpyridine 1
      oxides catalyzed by chiral pyridine 2,6-bis(5',5'-diphenyloxazoline)-Cu(II)
      complexes.
AB  - The catalytic enantioselective Friedel-Crafts reaction of indoles with 2
      enoylpyridine 1-oxides has been studied in the presence of chiral pyridine 2,6
      bis(5',5'-diphenyloxazoline)-Cu(II) complexes. The reaction furnished alkylated
      indoles in excellent yields (up to 97%) and enantioselectivities (up to 99% ee).

PMID- 18722460
TI  - Synthesis and application of alkenylstannanes derived from base-sensitive
      cyclopropenes.
AB  - In the presence of stoichiometric potassium fluoride, a range of base-sensitive
      cyclopropenes undergo direct stannylation using
      (pentafluoroethyl)tributylstannane. The resulting stannylcyclopropenes serve as
      precursors to a variety of tetrasubstituted cyclopropenes that might otherwise be
      difficult to access using alternative methods.

PMID- 18722461
TI  - Expanding the porphyrin pi-system by fusion with anthracene.
AB  - Synthesis of beta,meso,beta-anthracene triply fused and beta,meso-anthracene
      doubly fused porphyrins has been achieved via oxidative intramolecular ring
      closure of meso-(9-anthryl)porphyrins and meso-(1-anthryl)porphyrins,
      respectively. Fusion was only possible when the anthracene carried electron
      donating alkoxy substituents. The fused porphyrins exhibit strongly red-shifted
      UV-vis absorption spectra and reduced electrochemical HOMO-LUMO gaps (relative to
      the unfused tetraaryl porphyrin precursor).

PMID- 18722462
TI  - Total synthesis of the immunosuppressants myriocin and 2-epi-myriocin.
AB  - Total syntheses of the natural immunosuppressant myriocin (1) and the equipotent
      unnatural analogue 2-epi-myriocin (in protected form) have been achieved through
      a common strategy. The key transformations are the efficient synthesis of a
      quaternary (E)-vinylglycine by asymmetric deconjugative alkylation of a
      dehydroamino acid and an unusually highly diastereoselective dihydroxylation of
      the vinylglycine alkene.

PMID- 18722463
TI  - Macrocyclic nonviral vectors: high cell transfection efficiency and low toxicity
      in a lower rim guanidinium calix[4]arene.
AB  - New multivalent cationic lipids, one of them showing high efficiency and low
      toxicity in cell transfection, have been obtained by attaching guanidinium groups
      at the lower rim of calix[4]arenes.

PMID- 18722464
TI  - Protease activity in post-mortem red swamp crayfish (Procambarus clarkii) muscle
      stored in modified atmosphere packaging.
AB  - Protease activity during storage is thought to be an important contributor to
      decreased shelf life of fresh seafood. To examine this, three batches of red
      swamp crayfish ( Procambarus clarkii) tails, placed on trays, were packed with a
      polyvinyl chloride film (aerobic packaging or AP), under vacuum (vacuum packaging
      or VP), or under a modified atmosphere (MAP: 80% CO 2/10% O 2/10% N 2), and
      proteolytic activity was measured on days 0, 1, 3, 6, and 10 during storage at 2
      degrees C. The crude extract from the crayfish digestive system (gut) did not
      have an apparent role in muscle proteolysis as negligible proteolytic activity
      was detected. However, the loss of calpastatin (the endogenous calpain inhibitor)
      was identified in MAP-stored muscle samples on day 10, suggestive of high m
      calpain activity. Tail samples stored in AP showed no appreciable proteolysis,
      but those stored in MAP and VP showed significant decreases in the levels of 53,
      66, 71, and 110 kDa polypeptides during storage. The observed proteolytic
      activity and myofibrillar protein degradation did not correspond to muscle
      textural properties as the MAP samples had an increased toughness ( P < 0.05)
      after storage for 10 days. These findings suggest that other physicochemical
      mechanisms are involved in postmortem alteration in the crayfish muscle structure
      under the packaging systems investigated.

PMID- 18722465
TI  - Carcinogenicity of acrylamide: a computational study.
AB  - This paper reports a series of ab initio, density functional theory (DFT), and
      semiempirical molecular orbital (MO) calculations concerning the reaction between
      the ultimate carcinogen of acrylamide and guanine. Acrylamide--a product of the
      Maillard reaction--is present in a variety of fried and oven-cooked food. After
      intake, it is epoxidized by cytochrome P450 2E1 to yield the ultimate carcinogen-
      glycidamide. Effects of solvation were considered using the Langevin dipoles (LD)
      model of Florian and Warshel and the solvent reaction field (SCRF) model of
      Tomasi and co-workers. In silico activation free energies are in very good
      agreement with the experimental value of 22.8 kcal/mol. This agreement presents
      strong evidence in favor of the validity of the proposed S N2 reaction mechanism
      and points to the applicability of quantum chemical methods to studies of
      reactions associated with carcinogenesis. In addition, insignificant
      stereoselectivity of the studied reaction was predicted. Finally, the competing
      reaction of glycidamide with adenine was simulated, and the experimentally
      observed regioselectivity was successfully reproduced.

PMID- 18722466
TI  - Impact of retinal disease-associated RPE65 mutations on retinoid isomerization.
AB  - Pathogenic mutations in the RPE65 gene are associated with a spectrum of
      congenital blinding diseases in humans. We evaluated changes in the promoter
      region, coding regions, and exon/intron junctions of the RPE65 gene by direct
      sequencing of DNA from 36 patients affected with Leber's congenital amaurosis
      (LCA), 62 with autosomal recessive retinitis pigmentosa (arRP), and 21 with
      autosomal dominant/recessive cone-rod dystrophies (CORD). Fifteen different
      variants were found, of which 6 were novel. Interesting was Gly244Val, a novel
      mutation close to the catalytic center. To assess the role of this mutation in
      RPE65 inactivation, we performed detailed biochemical studies of the mutant along
      with a structural analysis of the 244 amino acid position with respect to amino
      acids known to be important for RPE65-dependent retinoid isomerization.
      Bicistronic plasmid expression of the RPE65 Gly244Val mutant and enhanced green
      fluorescent protein (EGFP) allowed us to document both its instability in
      cultured cells by cell sorting and immunoblotting methodology and its loss of
      RPE65-dependent isomerase activity by enzymatic assays. Further insights into the
      structural requirements for retinoid isomerization by RPE65 were obtained by
      using the carotenoid oxygenase (ACO) from Synechocystis (PDB accession code 2BIW
      ) as a structural template to construct a RPE65 homology model and locating all
      known inactivating mutations including Gly244Val within this model.

PMID- 18722467
TI  - Physiological consequences of selective suppression of synaptic transmission in
      developing cerebral cortical networks in vitro: differential effects on
      intrinsically generated bioelectric discharges in a living 'model' system for
      slow-wave sleep activity.
AB  - Within the context of an updated thorough review of the literature concerning
      activity-dependent cerebro-cortical development, a survey is made of recent
      experiments which utilize spontaneous spike-trains as the dependent variable in
      rodent neocortex cultures when synaptic transmission is interfered with during
      early ontogeny. Emphasis is placed on the complexity of homeostatic adaptations
      to reduced as well as intensified firing. Two kinds of adaptation are
      distinguished: (i) rapid recovery (within several hours) towards baseline levels
      despite sustained blockade of excitatory synaptic transmission, and (ii) the
      generation of essentially normal firing patterns in cultures assayed in control
      medium following development in the presence of excitatory receptor blockers. The
      former category of homeostatic responses is strongly dependent on the type of
      preparation, with isolated organotypic explants showing greatly limited
      plasticity in comparison with co-cultures of matching contralateral pieces of
      cortical tissue. In such co-cultures, compensatory excitatory drive manifests
      itself even when all three known types of ionotropic glutamate receptors are
      chronically blocked, and is then mediated by (muscarinic) cholinergic mechanisms
      which normally do not contribute measurably to spontaneous activity. The rapid
      return of high levels of spontaneous firing during sustained selective
      glutamatergic receptor blockade appears to protect neuronal cultures treated in
      this way from becoming hyperexcitable. In particular, quasi-epileptiform
      paroxysmal bursting upon return to control medium, such as appears in
      preparations where bioelectric activity has been totally suppressed during
      network formation, fails to appear in chronically receptor blocked cultures. On
      the contrary, desensitization of blocked glutamate receptors, as a physiological
      compensation for the up-regulation of non-blocked receptors, could be
      demonstrated for both the AMPA and the NMDA glutamate receptor sub-types. This
      wide range of homeostatic responses underscores the importance of spontaneous
      neuronal discharges for setting and maintaining an optimal balance between
      excitatory and inhibitory mechanisms in developing neocortical networks.

PMID- 18722468
TI  - Risperidone attenuates and reverses hyperthermia induced by 3,4
      methylenedioxymethamphetamine (MDMA) in rats.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational
      drug. Despite an increase in the number of fatalities related to its use, no
      definite therapeutic method has been established thus far. In the present study,
      risperidone's ability to attenuate MDMA-induced hyperthermia and its mechanism of
      action were investigated in rats. The pharmacological effect of MDMA was
      evaluated using microdialysis. In the body temperature experiment, administration
      of risperidone before and after MDMA administration significantly suppressed MDMA
      induced hyperthermia in a dose-dependent fashion. Furthermore, risperidone
      completely inhibited MDMA-induced hyperthermia at a low ambient temperature.
      Moreover, pretreatment with ritanserin, ketanserin, or R-96544, all of which are
      5-HT(2A)-receptor antagonists, significantly prevented MDMA-induced hyperthermia.
      On the other hand, pretreatment with WAY-100635 (a 5-HT(1A) receptor antagonist),
      SB 206553 (a 5-HT(2B/2C) receptor antagonist), or SB 242084 (a 5-HT(2C) receptor
      antagonist) did not prevent MDMA-induced hyperthermia. Pretreatment with
      haloperidol, which blocks the dopamine (DA) receptors D(2) and D(1),
      significantly prevented MDMA-induced hyperthermia. However, sulpiride and L
      741626, which are D(2) receptor blockers, did not prevent MDMA-induced
      hyperthermia. Pretreatment with SCH 23390 (a D(1) receptor antagonist)
      significantly prevented MDMA-induced hyperthermia. Furthermore,
      postadministration of ritanserin, haloperidol, and SCH23390 reversed MDMA-induced
      hyperthermia. These results demonstrate that the mechanism underlying the
      suppression of MDMA-induced hyperthermia by risperidone is primarily based on the
      drug's potent 5-HT(2A) receptor blocking effect, and to a lesser extent, on its
      D(1) receptor blocking effect. A microdialysis study showed that when MDMA
      (10mg/kg) was subcutaneously (s.c.) injected into the rats, the DA and serotonin
      (5-HT) levels in the anterior hypothalamus of the rats increased approximately 10
      and 50-fold, respectively, as compared to their preadministration levels. These
      increases in the DA and 5-HT levels after MDMA injection were significantly
      suppressed by pretreatment with risperidone (0.5mg/kg). This suggested that both
      the DA and 5-HT systems were involved in the induction of hyperthermia by MDMA.
      Taken together, the present study's results indicate that risperidone may be an
      effective drug for the treatment of MDMA-induced hyperthermia in humans.

PMID- 18722469
TI  - Overview of modifiers of methylmercury neurotoxicity: chemicals, nutrients, and
      the social environment.
AB  - It has been known for decades that methylmercury is a potent neurotoxicant, and
      that the developing brain is more susceptible to impairment as a result of
      methylmercury exposure than is the adult. Exposure to methylmercury is
      exclusively through consumption of fish and marine mammals. In recent years, the
      potential for protection against methylmercury toxicity by nutrients present in
      fish, particularly omega-3 fatty acids and selenium, has been explored in both
      epidemiological and experimental studies. There is evidence from several studies
      that fish consumption per se and methylmercury body burden act in opposition with
      regard to neuropsychological outcomes, whereas the evidence for a protective
      effect of specific nutrients is contradictory in both epidemiological and
      experimental studies published to date. The potential for methylmercury to
      interact with other chemicals present in marine food, particularly PCBs, has been
      explored in both animal models and human studies. Results may be both exposure-
      and endpoint-dependent. The Seychelles Islands study has explored the potential
      for the social environment to modify the effects of developmental methylmercury
      exposure. An understanding of the interactions of the multiple factors that
      determine the final behavioral outcome of exposure to methylmercury is crucial to
      risk assessment and risk management decisions.

PMID- 18722470
TI  - Spontaneous neuronal burst discharges as dependent and independent variables in
      the maturation of cerebral cortex tissue cultured in vitro: a review of activity
      dependent studies in live 'model' systems for the development of intrinsically
      generated bioelectric slow-wave sleep patterns.
AB  - A survey is presented of recent experiments which utilize spontaneous neuronal
      spike trains as dependent and/or independent variables in developing cerebral
      cortex cultures when synaptic transmission is interfered with for varying periods
      of time. Special attention is given to current difficulties in selecting suitable
      preparations for carrying out biologically relevant developmental studies, and in
      applying spike-train analysis methods with sufficient resolution to detect
      activity-dependent age and treatment effects. A hierarchy of synchronized nested
      burst discharges which approximate early slow-wave sleep patterns in the intact
      organism is established as a stable basis for isolated cortex function. The
      complexity of reported long- and short-term homeostatic responses to experimental
      interference with synaptic transmission is reviewed, and the crucial role played
      by intrinsically generated bioelectric activity in the maturation of cortical
      networks is emphasized.

PMID- 18722471
TI  - Simultaneous measurement of brain tissue oxygen partial pressure, temperature,
      and global oxygen consumption during hibernation, arousal, and euthermy in non
      sedated and non-anesthetized Arctic ground squirrels.
AB  - This study reports an online temperature correction method for determining tissue
      oxygen partial pressure P(tO2) in the striatum and a novel simultaneous
      measurement of brain P(tO2) and temperature (T(brain)) in conjunction with global
      oxygen consumption V(O2) in non-sedated and non-anesthetized freely moving Arctic
      ground squirrels (AGS, Spermophilus parryii). This method fills an important
      research gap-the lack of a suitable method for physiologic studies of tissue
      P(O2) in hibernating or other cool-blooded species. P(tO2) in AGS brain during
      euthermy (21.22+/-2.06 mmHg) is significantly higher (P=0.016) than during
      hibernation (13.21+/-0.46 mmHg) suggests brain oxygenation in the striatum is
      normoxic during euthermy and hypoxic during hibernation. These results in P(tO2)
      are different from blood oxygen partial pressure P(aO2) in AGS, which are
      significantly lower during euthermy than during hibernation and are actually
      hypoxic during euthermy and normoxic during hibernation in our previous study.
      This intriguing difference between the P(O2) of brain tissue and blood during
      these two physiological states suggests that regional mechanisms in the brain
      play a role in maintaining tissue oxygenation and protect against hypoxia during
      hibernation.

PMID- 18722472
TI  - Optimization of plasmid-only rescue of highly attenuated and temperature
      sensitive respiratory syncytial virus (RSV) vaccine candidates for human trials.
AB  - Respiratory syncytial virus (RSV) is the most common cause of severe
      bronchiolitis in infants and young children in the U.S. No licensed RSV vaccines
      are currently available. Established techniques for recovering RSV from cDNA
      utilize mammalian cells, such as HEp-2 or BSR T7/5, that are not currently
      suitable for vaccine manufacture. When using HEp-2 cells, co-infection with an
      attenuated vaccinia virus that expresses T7 RNA polymerase is also required. For
      human clinical trials, processes that do not require the use of helper viruses
      and minimize the use of animal derived materials must be developed to reduce the
      potential theoretical risk of transmitting adventitious agents such as BSE. RSV
      was generated by electroporating Vero cells from a well characterized cell bank
      with 6 plasmids expressing T7 RNA polymerase, the full-length anti-genomic RSV
      and RSV N, P, M2-1 and L. The process was optimized such that highly attenuated
      and temperature-sensitive RSV vaccine candidates could be recovered in a system
      completely free of animal derived components. Efficiencies of virus recovery
      ranged from 30% to 100%. Human metapneumovirus was also readily recovered,
      suggesting that this protocol is applicable for the production of clinical trial
      material of other non-segmented negative sense RNA viruses.

PMID- 18722473
TI  - Establishment of retroviral pseudotypes with influenza hemagglutinins from H1,
      H3, and H5 subtypes for sensitive and specific detection of neutralizing
      antibodies.
AB  - Pseudotype reporter viruses provide a safe, quantitative, and high-throughput
      tool for assessing antibody neutralization for many viruses, including high
      pathogenicity H5 and H7 influenza A strains. However, adapting this system to
      other influenza subtypes has been hampered by variations in the protease cleavage
      site of hemagglutinin (HA) that make it less susceptible to the cleavage required
      for infectivity. In this report several proteases, reporter vectors, and cell
      substrates were evaluated while optimizing pseudovirus production, and robust
      methods were established for sensitive and specific neutralization of pseudotypes
      carrying influenza H1, H3, and H5 subtype HA that correlates well with titers
      obtained in microneutralization assays involving replicating influenza virus
      These findings should facilitate broad use of HA-pseudotypes that remove the need
      for infectious virus in a range of applications, including neutralization assays
      for serological surveys of viral infection and evaluations of vaccine sera.

PMID- 18722474
TI  - Detection and differentiation of human papillomavirus genotypes HPV-6 and HPV-11
      by FRET-based real-time PCR.
AB  - A real-time PCR (RT-PCR) assay was developed based on fluorescence resonance
      energy transfer (FRET) hybridization probe technology, allowing very sensitive
      and specific detection of HPV-6 and HPV-11, reliable differentiation of HPV-6 and
      HPV-11, as well as prototypic and non-prototypic HPV-6 genomic variants, in a
      single PCR reaction. The primers and probe were designed on the basis of multiple
      alignments of 74 HPV-6 E2 gene sequences and 20 HPV-11 E2 gene sequences. Testing
      on defined plasmid standards showed that the RT-PCR allowed simple and reliable
      identification of HPV-6 and HPV-11 using type specific amplification followed by
      probe-specific post-amplification dissociation analysis. Sensitivity, assessed by
      probit analysis at a 95% detection level, was 42.9, 43.4, and 25.3 DNA copies per
      assay for prototypic and non-prototypic HPV-6 variants and HPV-11, respectively.
      The results obtained by the developed assay on 51 HPV DNA-negative samples and
      149 HPV DNA-positive samples, including 81 HPV-6 positive samples (19 prototypic
      and 62 non-prototypic HPV-6 variants), 28 HPV-11 positive samples, 10 samples of
      HPV-44 and HPV-74 (the closest relatives of HPV-6 and HPV-11) and 30 samples of
      15 other important alpha HPV, showed complete agreement with those obtained with
      the INNO-LiPA human papillomavirus (HPV) Genotyping Assay and HPV-6 E2 and E6
      gene sequencing.

PMID- 18722475
TI  - Engineering enhancement of the immune response to HBV DNA vaccine in mice by the
      use of LIGHT gene adjuvant.
AB  - DNA vaccines could induce protective immune responses in several animal models.
      Many strategies have been employed to improve the effect of nucleic acid
      vaccines. LIGHT is a member of the TNF superfamily and functions as a co
      stimulatory molecule for T cell proliferation. In the study, the immunogenicity
      in the induction of humoral and cellular immune responses by HBV DNA vaccine and
      the adjuvant effect of LIGHT were studied in a murine model. The eukaryotic
      expression plasmid pcDNA-L was constructed by inserting mouse LIGHT gene into the
      vector pcDNA3.1(+). In vitro expression of LIGHT was detected by RT-PCR and
      indirect immunofluorescence assay in transfected HeLa cells. MLR assay showed
      that LIGHT-transfected DCs induced markedly higher allogeneic lymphocyte
      proliferation than pcDNA-transfected DCs and untreated DCs at all dilutions.
      After BALB/c mice were immunized by three intramuscular injections of the HBV DNA
      vaccine plasmids alone or in combination with LIGHT expression plasmids, the
      different levels of anti-HBV immune responses were measured comparable to the
      control groups immunized with parent plasmid pcDNA or PBS. The HBsAg-specific
      splenocytes proliferation and specific cytotoxic activities of splenic CTLs in
      the coinoculation group were both significantly higher than those in the HBV DNA
      single inoculation group, and an enhancement of antibody response was also
      observed in the coinoculation group compared with the single inoculation group.
      Taken together, coimmunization of HBV DNA vaccine plasmids and LIGHT expression
      plasmids can elicit stronger humoral and cellular immune responses in mice than
      HBV DNA vaccine plasmids alone, and LIGHT may be an effective immunological
      adjuvant in HBV DNA vaccination.

PMID- 18722476
TI  - Use of Luminex xMAP-derived Bio-Plex bead-based suspension array for specific
      detection of PPV W and characterization of epitopes on the coat protein of the
      virus.
AB  - A panel of monoclonal antibodies (MAbs) directed against the N-terminus region of
      the coat protein (CP) of strain PPV W (isolate 3174) was generated by immunizing
      mice with recombinant peptides. The best performing MAbs were identified as 2C3
      and 10G7. MAb 2C3 was selected for comparison of a standard TAS-ELISA protocol
      with a Luminex xMAP technology-derived bead-based suspension array system
      described as a triple antibody sandwich-microsphere immunoassay (TAS-MIA). TAS
      MIA was as sensitive as TAS-ELISA for the specific detection of PPV W in
      herbaceous and woody hosts. It was completed in 4h, and used less reagents.
      Epitope recognition analysis was carried out using a set of overlapping synthetic
      pin-bound peptides (Mimotopes). Peptides (2)DEEDD(6) and (46)MFNPV(50) were the
      epitopes recognized most commonly by the best performing MAbs. Linear epitope
      prediction of B-cell recognition sites confirmed that both peptides fall within
      highly antigenic and accessible regions. The second glutamic acid residue of the
      epitope is crucial for MAb recognition, and the context of the epitope is as
      important as the sequence of the epitope. The results obtained in ELISA, Western
      blot, and TAS-MIA correlated with B-cell recognition prediction. This is an
      effective approach to identify suitable antigenic epitopes that generate
      antibodies for use in reliable diagnostic procedures. This is the first report of
      the detection of a plant virus using the Luminex xMAP bead-based suspension array
      system.

PMID- 18722477
TI  - Precise endogenous control of involvement of right and left visual structures in
      assessment by zebrafish.
AB  - Birds and fish use monocular viewing to bring to bear appropriate lateralised
      specialisations. In larval zebrafish, persistent left eye (LE) viewing of their
      own reflection is interrupted by a series of brief 'events', in which the right
      eye has equal use. These recur with precise 160 s periodicity, with the first
      beginning after 40s, and allow right and left mechanisms to assess the
      reflection. In a strain in which persistent LE bias ceased after about 2 min,
      events were still marked by a brief period of frontal viewing, immediately after
      the time of each event ('after-effects'). Such viewing allows simultaneous access
      by both right and left visual systems, and may be associated therefore with
      interaction, perhaps involving linkage of initially independent traces. Events
      appeared to cease after the maximal after-effect following the third event. Older
      fish show changes in overt behaviour immediately after event times; again the
      third event ends this. Processes associated with events thus progressively change
      what is available to recall. Domestic chicks show enhanced evocation of response
      (e.g. sex, defense) to fellows, with the LE but not the right, if exposed to
      light during embryonic development. In zebrafish (where light may act by an
      epiphyseal route) we found that after dark development, viewing bias peaked at
      the time of each event, with LE use at the first and right at the second. The
      main factor determining the outcome of right/left competition appears here to be
      recency of access to viewing.

PMID- 18722478
TI  - Medial prefrontal cortex and nucleus accumbens core are involved in retrieval of
      the methamphetamine-associated memory.
AB  - Immunohistochemical Fos staining has proven to be a method to identify the
      neurons that are activated by stimulation. Although methamphetamine (MA)
      conditioned place preference (CPP) memory was long-lasting, how this memory was
      established and retrieved remained unknown. We used the vehicle- and MA
      conditioned environment (including cues and context) to reactivate the MA-CPP
      memory in mice. In the limbic system, Fos-positive neurons were examined
      following retrieval of the MA-CPP memory. We demonstrated that the current
      conditioning procedure produced reliable MA-CPP performance. Moreover, enhanced
      Fos expressions were found in the medial prefrontal cortex and the core of the
      nucleus accumbens after reactivation of the MA-CPP memory. Furthermore,
      familiarity with the environmental cues/context was found to significantly
      enhance Fos expressions in dorsal striatum and dentate gyrus. Nucleus accumbens
      shell, basolateral or lateral amygdala, in this regard, did not seem to be
      involved in retrieval of the MA-CPP memory. These results, taken together,
      suggest that the medial prefrontal cortex and the core of the nucleus accumbens
      are anatomical substrates responsible for reactivation of the MA-CPP memory.

PMID- 18722479
TI  - Object properties and cognitive load in the formation of associative memory
      during precision lifting.
AB  - When we manipulate familiar objects in our daily life, our grip force anticipates
      the physical demands right from the moment of contact with the object, indicating
      the existence of a memory for relevant object properties. This study explores the
      formation and consolidation of the memory processes that associate either
      familiar (size) or arbitrary object features (color) with object weight. In the
      general task, participants repetitively lifted two differently weighted objects
      (580 and 280 g) in a pseudo-random order. Forty young healthy adults participated
      in this study and were randomly distributed into four groups: Color Cue Single
      task (CCS, blue and red, 9.8(3)cm(3)), Color Cue Dual task (CCD), No Cue (NC) and
      Size Cue (SC, 9.8(3) and 6(3)cm(3)) group. All groups performed a repetitive
      precision grasp-lift task and were retested with the same protocol after a 5-min
      pause. The CCD group was also required to simultaneously perform a memory task
      during each lift of differently weighted objects coded by color. The results show
      that groups lifting objects with arbitrary or familiar features successfully
      formed the association between object weight and manipulated object features and
      incorporated this into grip force programming, as observed in the different
      scaling of grip force and grip force rate for different object weights. An
      arbitrary feature, i.e., color, can be sufficiently associated with object
      weight, however with less strength than the familiar feature of size. The
      simultaneous memory task impaired anticipatory force scaling during repetitive
      object lifting but did not jeopardize the learning process and the consolidation
      of the associative memory.

PMID- 18722480
TI  - Voluntary exercise in C57 mice is anxiolytic across several measures of anxiety.
AB  - Voluntary wheel running in rodents is associated with a number of adaptive
      behavioral and physiological effects including improved learning, reduction in
      stress-associated behaviors, neurogenesis, angiogenesis, increases in
      neurotrophic factors, and changes in several signaling molecules. Exercise has
      also been reported to reduce anxiety-like behaviors. However, other studies have
      failed to find an anxiolytic effect of exercise. The inconsistencies in the
      literature may contribute to the scarcity of data examining the physiological
      correlates of the anxiolytic effect of exercise. Here we show that 2 weeks of
      voluntary exercise in male C57 mice is associated with reduced anxiety as
      measured with acoustic startle, stress-induced hyperthermia, social interaction,
      light-enhanced startle, and some, but not all, measures in the open field. A
      great deal is known about the neural circuits underlying anxiety. Given the
      consistency of the anxiolytic effect of voluntary exercise across several
      measures, it is now possible to begin a systematic analysis of the physiological
      basis of the anxiolytic effect of exercise.

PMID- 18722481
TI  - The importance of chromogranin A in the development and function of endocrine
      pancreas.
AB  - BACKGROUND: Chromogranin (Cg) A is expressed in neuroendocrine and neuronal
      tissues. It is involved in the generation of secretory granules and is cleaved to
      form biologically active peptides. Targeted ablation of the Chga gene resulted in
      increased plasma catecholamines, high blood pressure, and decreased size and
      number of adrenal medullary chromaffin granules. The aim of this study was to
      determine whether Chga null mice display changes in the morphology and function
      of the endocrine pancreas. MATERIALS AND METHODS: Sections of pancreata from Chga
      /-, Chga+/- and Chga+/+ mice, were immunostained with antibodies against
      synaptophysin, CgA, CgB, secretogranin II and the four major pancreatic islet
      hormones. Plasma was analysed for glucose, insulin, glucagon, somatostatin and
      pancreatic polypeptide (PP). RESULTS: CgA epitopes were undetectable in the
      islets of Chga-/- animals. CgB and secretogranin II epitopes were expressed in
      the islets of all animal groups albeit with decreased expression in Chga-/-
      islets. The islet number and size were decreased in the Chga-/- animals compared
      with Chga+/+. The proportion of insulin cells was decreased but somatostatin and
      PP cells were increased in Chga-/- mice compared to Chga+/+ mice. The nuclear
      size was decreased in insulin cells and increased in somatostatin cells in Chga-/
      mice. Plasma insulin level was markedly decreased in the Chga-/- mice although
      fasting plasma glucose and glucagon were normal. CONCLUSION: Ablation of the Chga
      gene affected the islet volume, the composition, distribution and nuclear size of
      islet cell types and plasma insulin concentration. Our data indicate decreased
      insulin cell function and increased glucagon cell function. Our study shows that
      CgA exerts a significant influence on the endocrine pancreas with importance in
      maintaining islet volume, cellular composition and function.

PMID- 18722482
TI  - Induction of angiogenesis by murine resistin: putative role of PI3-kinase and NO
      dependent pathways.
AB  - Adipose tissue is a highly active endocrine organ, secreting bioactive molecules,
      adipokines, into the circulation. Obesity results in dysregulated adipokine
      secretion, contributing to pathophysiologies associated with this disorder,
      including insulin resistance and cardiovascular disease. OBJECTIVES: To establish
      whether resistin, a novel bioactive molecule produced by murine adipose tissue,
      and implicated in insulin resistance in rodents, can induce angiogenic responses
      in aortic tissues and endothelial cells in vitro, and to investigate the signal
      transduction pathways involved in these responses. RESULTS: Recombinant murine
      resistin (5-100 ng ml(-1)) induced sprouting of cellular networks and migration
      from murine aortic arch explants, primary aortic endothelial cells and in a
      'wound healing' model utilising murine b.End5 endothelioma cells. The increased
      migration and sprouting of endothelial cells, due to resistin, were blocked by
      wortmannin (100 nM) and LY294002 (10 microM), inhibitors of phosphatidylinositol
      3-kinase (PI3K), and accompanied by PI3K-dependent phosphorylation of Akt;
      moreover, while the changes were not associated with altered production of nitric
      oxide (NO), resistin-induced angiogenic responses were inhibited by IKK Inhibitor
      X (5 microM), an inhibitor of activation of nuclear factor (NF)-kappaB.
      CONCLUSIONS: Murine resistin induces endothelial cell migration and sprouting of
      cellular networks via a mechanism which appears dependent upon PI3K and NF-kappaB
      activity, but independent of altered NO production. Resistin may contribute to
      angiogenic responses sustaining adipose tissue expansion, or in arterial tissues
      distal to this site.

PMID- 18722483
TI  - Genome organization: balancing stability and plasticity.
AB  - The cell needs to stably maintain its genome and protect it from uncontrolled
      modifications that would compromise its function. At the same time, the genome
      has to be a plastic structure that can dynamically (re)organize to allow the cell
      to adopt different functional states. These dynamics occur on the nanometer to
      micrometer length scale, i.e. ranging from the level of single proteins up to
      that of whole chromosomes, and on a microsecond to hour time scale. Here, we
      review different contributions to the dynamic features of the genome, describe
      how they are determined experimentally, and discuss the results of these
      measurements in terms of how the requirements for stability and plasticity are
      accommodated with specific activities in the nucleus.

PMID- 18722484
TI  - SRC-dependent signalling regulates actin ruffle formation induced by
      glycerophosphoinositol 4-phosphate.
AB  - The glycerophosphoinositols are diffusible phosphoinositide metabolites reported
      to modulate actin dynamics and tumour cell spreading. In particular, the membrane
      permeant glycerophosphoinositol 4-phosphate (GroPIns4P) has been shown to act at
      the level of the small GTPase Rac1, to induce the rapid formation of membrane
      ruffles. Here, we have investigated the signalling cascade involved in this
      process, and show that it is initiated by the activation of Src kinase. In NIH3T3
      cells, exogenous addition of GroPIns4P induces activation and translocation of
      Rac1 and its exchange factor TIAM1 to the plasma membrane; in addition, in in
      vitro assays, GroPIns4P favours the formation of a protein complex that includes
      Rac1 and TIAM1. Neither of these processes involves direct actions of GroPIns4P
      on these proteins. Thus, through the use of specific inhibitors of tyrosine
      kinases and phospholipase C (and by direct evaluation of kinase activities and
      inositol 1,4,5-trisphosphate production), we show that GroPIns4P activates Src,
      and as a consequence, phospholipase Cgamma and Ca(2+)/calmodulin kinase II, the
      last of which directly phosphorylates TIAM1 and leads to TIAM1/Rac1-dependent
      ruffle formation.

PMID- 18722485
TI  - Membrane progestin receptors alpha and gamma in renal epithelium.
AB  - Sex hormones have broader effects than regulating reproductive functions. Recent
      identification of membrane progestin receptors expressed in kidney prompted us to
      investigate their putative involvement in the renal effects of this hormone. We
      first focused our investigations on mPRalpha and gamma by analyzing three
      parameters 1/ their distribution along the mouse nephron and their subcellular
      location in native kidney, 2/ the ability of progesterone to stimulate ERK
      pathway and/or Ca(2+) release from internal stores in native kidney structures
      and 3/ the cellular localization of mPRalpha and its molecular determinants in
      heterologous expression system. We observed that 1/ mPRalpha expression is
      restricted to proximal tubules of both male and female mice whereas mPRgamma
      exhibits a much broader expression all along the nephron except the glomerulus,
      2/ mPRalpha and gamma are not localized at the plasma membrane in native kidney,
      3/ this expression does not permit either progesterone-induced ERK
      phosphorylation or Ca(2+) release and 4/ in HEK transfected cells, mPRalpha
      localizes in the endoplasmic reticulum (ER) due to a C-terminal ER retention
      motif (-KXX). Therefore, we have characterized mPRs in kidney but their role in
      renal physiology remains to be elucidated.

PMID- 18722486
TI  - Expression of v-cath gene from HearNPV in tobacco confers an antifeedant effect
      against Helicoverpa armigera.
AB  - Biotechnology solutions for insect control on crops largely depend on the
      expression of Bacillus thuringiensis insecticidal proteins to kill pests. V-CATH,
      a cathepsin L-like cysteine protease from baculoviruses, has been shown to play
      an essential role in host insect liquefaction. In this study, the v-cath gene
      from Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) was cloned into
      the pBI121 binary vector under the control of CaMV35S promoter, and was expressed
      in tobacco via Agrobacterium-mediated transformation. PCR and RT-PCR analyses of
      T(1) kanamycin-resistant tobacco progeny plants confirmed the integration and
      transcription of the v-cath gene. Using a leaf-disk bioassay, antifeedant
      activity toward H. armigera was tested. Our result showed that, when feeding the
      first-instar larvae of H. armigera with leaves of transgenic plants, the v-cath
      transgene expression has a profound antifeedant effect. Most importantly, the
      growth and development of the insect were inhibited when transferred from leaf
      feeding to artificial diet. Our result demonstrated that v-cath gene from
      baculovirus induced antifeedant effect against H. armigera, resulted in larval
      stunting and retarded insect development, and has the potential to be used as an
      alternative way to generate transgenic plants for insect pest control.

PMID- 18722487
TI  - The N protein of Tomato spotted wilt virus (TSWV) is associated with the
      induction of programmed cell death (PCD) in Capsicum chinense plants, a
      hypersensitive host to TSWV infection.
AB  - In sweet pepper, the Tsw gene, originally described in Capsicum chinense, has
      been widely used as an efficient gene for inducing a hypersensitivity response
      (HR) derived Tomato spotted wilt virus (TSWV) resistance. Since previously
      reported studies suggested that the TSWV-S RNA mutation(s) are associated with
      the breakdown of Tsw mediated TSWV resistance in peppers, the TSWV genes N
      (structural nucleocapsid protein) and NS(S) (non-structural silencing suppressor
      protein) were cloned into a Potato virus X (PVX)-based expression vector, and
      inoculated into the TSWV-resistant C. chinense genotype, PI 159236, to identify
      the Tsw-HR viral elicitor. Typical HR-like chlorotic and necrotic lesions
      followed by leaf abscission were observed only in C. chinense plants inoculated
      with the PVX-N construct. Cytopathological analyses of these plants identified
      fragmented genomic DNA, indicative of programmed cell death (PCD), in mesophyll
      cell nuclei surrounding PVX-N-induced necrotic lesions. The other constructs
      induced only PVX-like symptoms without HR-like lesions and there were no
      microscopic signs of PCD. The mechanism of TSWV N-gene HR induction is apparently
      species specific as the N gene of a related tospovirus, Tomato chlorotic spot
      virus, was not a HR elicitor and did not cause PCD in infected cells.

PMID- 18722488
TI  - The begomoviruses Honeysuckle yellow vein mosaic virus and Tobacco leaf curl
      Japan virus with DNAbeta satellites cause yellow dwarf disease of tomato.
AB  - The complete nucleotide sequences of two begomoviruses (Nara virus-1 and Nara
      virus-2), a satellite DNA (DNAbeta-Nara) and defective DNAs were obtained from
      honeysuckle (Lonicera japonica) showing characteristic yellow vein mosaic
      symptoms in Nara Prefecture, Japan. One begomovirus (Ibaraki virus) and a
      satellite DNA (DNAbeta-Ibaraki) was isolated and cloned from honeysuckle plants
      exhibited typical yellowing of veins and small elliptical shaped enations along
      veins on the under side of the leaves in Ibaraki Prefecture, Japan. The genome
      organization of the three viruses is the same as those of other Old World
      monopartite begomoviruses. Nara virus-1 had overall nucleotide sequence identity
      with Nara virus-2 of 94% and Ibaraki virus of 90%. DNAbeta-Nara had overall
      nucleotide sequence identity with DNAbeta-Ibaraki of 83%. Comparison of the
      nucleotide sequences with other begomoviruses revealed that Nara virus-1 and Nara
      virus-2 are strains of Honeysuckle yellow vein mosaic virus (HYVMV), hence named
      as HYVMV-Nara1 and HYVMV-Nara2, whereas Ibaraki virus was a strain of Tobacco
      leaf curl Japan virus (TbLCJV), designated as TbLCJV-Hs[Iba]. HYVMV-Nara1 and
      HYVMV-Nara2 have hybrid genomes, which are likely to have formed recombination
      between HYVMV and TbLCJV. TbLCJV-Hs[Iba] or HYVMV-Nara2 could infect and cause
      yellowing, leaf crinkling and stunting symptoms when partial tandem dimeric
      constructs were agroinoculated on tomato plants. However, in the presence of
      DNAbeta, both TbLCJV-Hs[Iba] or HYVMV-Nara2 produced more severe stunting
      symptoms in tomato plants. Therefore, these viruses along with their satellites
      are causal agents of tomato yellow dwarf disease in Japan, and honeysuckle acts
      as a potential reservoir host. Previously available evidence indicated that
      DNAbeta elements do not contain iteron sequences of their helper viruses; hence
      this is the first evidence that DNAbeta satellites have the iteron of their
      helper virus.

PMID- 18722489
TI  - Prevention of MDR development in leukemia cells by micelle-forming polymeric
      surfactant.
AB  - Doxorubicin (Dox) incorporated in nanosized polymeric micelles, SP1049C, has
      shown promise as monotherapy in patients with advanced esophageal carcinoma. The
      formulation contains amphiphilic block copolymers, Pluronics, that exhibit the
      unique ability to chemosensitize multidrug resistant (MDR) tumors by inhibiting P
      glycoprotein (Pgp) drug efflux system and enhancing pro-apoptotic signaling in
      cancer cells. This work evaluates whether a representative block copolymer,
      Pluronic P85 (P85) can also prevent development of Dox-induced MDR in leukemia
      cells. For in vitro studies murine lymphocytic leukemia cells (P388) were exposed
      to increasing concentrations of Dox with/without P85. For in vivo studies, BDF1
      mice bearing P388 ascite were treated with Dox or Dox/P85. The selected P388 cell
      sublines and ascitic tumor-derived cells were characterized for Pgp expression
      and functional activity (RT-PCR, Western Blot, rhodamine 123 accumulation) as
      well as Dox resistance (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay). The global gene expression was determined by oligonucleotide gene
      microarrays. We demonstrated that P85 prevented development of MDR1 phenotype in
      leukemia cells in vitro and in vivo as determined by Pgp expression and
      functional assays of the selected cells. Cells selected with Dox in the presence
      of P85 in vitro and in vivo exhibited some increases in IC(50) values compared to
      parental cells, but these values were much less than IC(50) in respective cells
      selected with the drug alone. In addition to mdr1, P85 abolished alterations of
      genes implicated in apoptosis, drug metabolism, stress response, molecular
      transport and tumorigenesis. In conclusion, Pluronic formulation can prevent
      development of MDR in leukemia cells in vitro and in vivo.

PMID- 18722490
TI  - A convenient method for preparation of biologically active recombinant CHH of the
      kuruma prawn, Marsupenaeus japonicus, using the bacterial expression system.
AB  - Crustacean hyperglycemic hormone (CHH) not only plays an important role in the
      modulation of hemolymph glucose level but also functions in other biological
      events including molting, reproduction and stress response. Of the six CHHs
      characterized in Marsupenaeus japonicus, an expression system for recombinant Pej
      SGP-VII (rPej-SGP-VII-amide) has not yet been established. Here, we established a
      procedure using a Nus-tag for solubilization, thereby soluble and biologically
      active rPej-SGP-VII-amide could successfully be obtained by a simpler procedure
      than previous ones used for producing other recombinant Pej-SGPs (Pej-SGP-I, III
      and IV). It was found that rPej-SGP-VII-amide thus obtained had the correct
      arrangement of intramolecular disulfide bonds and helix-rich secondary structure.
      The established expression system for rPej-SGP-VII-amide may be applicable for
      the preparation of other recombinant CHHs.

PMID- 18722491
TI  - Human leukocyte antigen class II allele association to disease progression in
      Iranian patients with chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia in
      Western countries, but its incidence is low in Asian populations. In the present
      study we determined the frequency of DRB1 and DQB1 alleles in 87 Iranian CLL
      patients and 100 healthy controls using a polymerase chain reaction (PCR)
      technique. An increased frequency of DRB1*07 (p = 0.04), DQB1*06 (p = 0.01)
      alleles, and DRB1*13/DQB1*03 haplotype (p = 0.01) and decreased frequency of the
      DQB1*03 (p = 0.01) allele were observed in our patients compared with healthy
      controls. Comparison between patients with indolent (n = 42) and progressive (n =
      38) disease revealed a significant increase in DRB1*04 and DRB5 alleles in
      progressive patients. Similarly, a higher frequency of DRB5 (p = 0.01) allele was
      observed in CD38(+) compared with CD38(-) patients. Classification of the
      patients into immunoglobulin variable region heavy-chain genes mutated and
      unmutated subtypes did not reveal significant differences for the expression of
      any of the HLA alleles or haplotypes between these two subtypes. Our findings
      observed in an Iranian population indicate that CLL could be associated with
      distinct HLA class II alleles and haplotypes of which the DQB1*06 allele and
      DRB1*13/DQB1*03 haplotype have not already been reported in CLL patients from
      other ethnic backgrounds. Some HLA class II alleles may contribute to disease
      progression in CLL.

PMID- 18722492
TI  - Decline in influenza-associated mortality among Dutch elderly following the
      introduction of a nationwide vaccination program.
AB  - With a retrospective nationwide cohort study in the Netherlands over 1992-2003,
      using mortality and viral surveillance data, the aim was to assess by means of
      rate difference methods the influenza-associated mortality in the elderly before
      and after the introduction of a nationwide influenza vaccination program in 1996
      (vaccination coverage raised from below 50 to 80%). The average annual influenza
      associated mortality declined in the years before and after the introduction from
      131 to 105 per 100,000 persons (relative risk 0.80). The decline was largest in
      the age group 65-69 years (relative risk 0.54) and less in those aged 75 years
      and older. Validation by Serfling-type regression analysis revealed similar
      results. In conclusion, routine influenza vaccination among Dutch elderly was
      associated with a significant decrease in influenza-associated mortality, notably
      in those aged 65-69 years.

PMID- 18722494
TI  - Protective immunity induced by rPb27 of Paracoccidioides brasiliensis.
AB  - A cDNA coding for an antigenic protein (rPb27) from the pathogenic fungus
      Paracoccidioides brasiliensis was cloned and its protective activity was
      determined against paracoccidioidomycosis (PCM). The cDNA sequence contained an
      open reading frame (ORF) of 660 base pairs encoding a protein of 219 amino acids
      with a predicted molecular weight of 25kDa. The deduced amino acid sequence
      exhibited 100% identity to the 27kDa P. brasiliensis hypothetic protein (access
      number AA49615). The complete coding cDNA was cloned into a pGEX 4T-2 plasmid and
      expressed in Escherichia coli as a glutathione-S-transferase-tagged (GST)
      recombinant protein. Mice immunized with purified rPb27 were able to develop high
      levels of IgG2b, moderate levels of IgG1 and low levels of IgG2a. At the same
      time the levels of TGF-beta and IFN-gamma were high while a very low production
      of IL-10 was verified. Using confocal microscopy with anti-rPb27 mouse serum
      against P. brasiliensis yeast forms, surface and cytosolic staining pattern were
      observed. Moreover, immunization of mice with this antigen induced a significant
      degree of protection in the lungs (93%), liver (93%) and spleen (100%) at 60 days
      after challenge with infection. Thus, the granulomatous lesions revealed a
      greater degree of compaction and organization, with few lesions in the lungs and
      no dissemination of the fungus to other organs. These results showed that a
      recombinant protein of P. brasiliensis (rPb27) promoted acquired protection
      against infection with P. brasiliensis yeast forms, suggesting the use of this
      protein for future development as a prophylactic vaccine for PCM.

PMID- 18722495
TI  - The ethics of mandatory vaccination against influenza for health care workers.
AB  - Vaccination of health care workers (HCW) in long-term care results in indirect
      protection of patients who are at high-risk for influenza. The voluntary uptake
      of influenza vaccination among HCW is generally low. We argue that institutions
      caring for frail elderly have the responsibility to implement voluntary
      programmes for vaccination against influenza of HCW. When uptake falls short a
      mandatory programme may be justified. The main justification stems from the duty
      of care givers not to harm one's patient when one knows there is a significant
      risk of harm and the intervention to reduce this chance has a favourable balance
      of benefit over burdens and risks.

PMID- 18722493
TI  - Lipid A mimetics are potent adjuvants for an intranasal pneumonic plague vaccine.
AB  - An effective intranasal (i.n.) vaccine against pneumonic plague was developed.
      The formulation employed two synthetic lipid A mimetics as adjuvant combined with
      Yersinia pestis-derived V- and F1-protective antigens. The two nontoxic lipid A
      mimetics, classed as amino-alkyl glucosaminide 4-phosphates (AGPs) are potent
      ligands for the Toll-like receptor (TLR) 4. Using a murine (BALB/c) pneumonic
      plague model, we showed a single i.n. application of the vaccine provided 63%
      protection within 21 days against a Y. pestis CO92 100 LD50 challenge. Protection
      reached 100% by 150 days. Using a homologous i.n. 1 degrees /2 degrees dose
      regimen, with the boost administered at varying times, 63% protection was
      achieved within 7 days and 100% protection was achieved by 21 days after the
      first immunization. Little or no protection was observed in animals that received
      antigens alone, and no protection was observed when the vaccine was administered
      to BALB/c TLR4 mutant mice. Vaccine-induced serum IgG titers to F1 and V-antigen
      were reflected in high titers for IgG1 and IgG2a, the latter reflecting a bias
      for a cell-mediated (TH1) immune response. This intranasal vaccine showed 90%
      protection in Sprague-Dawley rats challenged with 1000 LD50. We conclude that
      lipid A mimetics are highly effective adjuvants for an i.n. plague vaccine.

PMID- 18722496
TI  - Aging increases the susceptibility to develop anhedonia in male rats.
AB  - The objective of this study was to establish the effect of aging on the
      development of anhedonia, a core feature of depression. Young and old male Wistar
      rats (of around 3-5 and 12-15 months, respectively) were exposed to a chronic
      variable stress (CVS) schedule for 3 weeks. CVS produced anhedonia, indicated by
      a reduction in the intake of a sucrose solution (1%), in 8 out of 23 (35%) young
      rats and in 19 out of 26 (73%) old rats, implying that old animals are more
      susceptible to stress and develop anhedonia more readily than young animals.
      Young and old anhedonic rats showed a similar temporal course in the reduction of
      sucrose consumption, reaching the anhedonic state after 2 weeks of CVS exposure.
      Compared with young animals, old rats had lower basal serum testosterone and
      estradiol levels. The systemic levels of corticosterone did not vary between both
      age groups. No significant pathological condition was detected in old animals. It
      is suggested that the higher susceptibility to develop anhedonia in male rats
      could be associated to neuroendocrine changes consequent to aging.

PMID- 18722497
TI  - Studying the genotoxicity of vincristine on human lymphocytes using comet assay,
      micronucleus assay and TCR gene mutation test in vitro.
AB  - The results of our previous investigation for workers occupationally exposed to
      vincristine (VCR) indicated that the genetic damage was detectable with comet
      assay, cytokinesis-block micronucleus (CBMN) assay and housekeeping gene mutation
      tests. In order to determine the results of above investigation and to inquire
      further the characteristics of genotoxicity of VCR, the cytogenetic effects of
      VCR on human lymphocytes were assessed with comet assay, CBMN assay and T-cell
      receptor (TCR) gene mutation test in vitro. The lymphocytes from two healthy
      donors were incubated for 24h at doses of 0.00, 0.01, 0.02, 0.04, and
      0.08microgml(-1) VCR. The results of the present experiment showed that VCR not
      only could induce DNA damage, increase significantly micronucleus frequencies and
      the apoptotic cell ratios and decrease the nuclear division index (NDI) with dose
      response relationship, but also could produce nucleoplasmic bridges (NPBs), a
      biomarker of DNA misrepair and/or telomere end-fusions and nuclear buds (NBUDs),
      a biomarker of elimination of amplified DNA and/or DNA repair complexes.
      Moreover, VCR could enhance TCR gene mutation frequency (Mf-TCR) of human
      lymphocytes. There was good correlation between the parameters (mean tail length,
      mean tail moment, micronucleus frequency, micronucleated frequency and Mf-TCR).
      The results of present study supported the results of our previous investigation
      for workers occupationally exposed to VCR, and the genotoxicity of VCR was
      determined at the different genetic end-points in vitro.

PMID- 18722498
TI  - Protein cooperation: from neurons to networks.
AB  - A constant pattern through the development of cellular life is that not only
      cells but also subcellular components such as proteins, either being enzymes,
      receptors, signaling or structural proteins, strictly cooperate. Discerning how
      protein cooperation originated and propagates over evolutionary time, how
      proteins work together to a shared outcome far beyond mere interaction, thus
      represents a theoretical and experimental challenge for evolutionary, molecular,
      and computational biology, and a timely fruition also for biotechnology. In this
      review, we describe some basic principles sustaining not only cellular but
      especially protein cooperative behavior, with particular emphasis on
      neurobiological systems. We illustrate experimental results and numerical models
      substantiating that bench research, as well as computer analysis, indeed concurs
      in recognizing the natural propensity of proteins to cooperate. At the cellular
      level, we exemplify network connectivity in the thalamus, hippocampus and basal
      ganglia. At the protein level, we depict numerical models about the receptosome,
      the protein machinery connecting neurotransmitters or growth factors to specific,
      unique downstream effector proteins. We primarily focus on the purinergic P2/P1
      receptor systems for extracellular purine and pyrimidine nucleotides/nucleosides.
      By spanning concepts such as single-molecule biology to membrane computing, we
      seek to stimulate a scientific debate on the implications of protein cooperation
      in neurobiological systems.

PMID- 18722499
TI  - Applying the polyvagal theory to children's emotion regulation: Social context,
      socialization, and adjustment.
AB  - Effective emotion regulation is essential for children's positive development.
      Polyvagal theory provides a framework for understanding how parasympathetic
      regulation of cardiac activity contributes to children's adaptive versus
      maladaptive functioning. Maintenance of cardiac respiratory sinus arrhythmia
      (RSA) under social challenge should support emotion regulation and behavioral
      adjustment. Children's effective parasympathetic regulation and behavioral
      adjustment should be supported by appropriate parental socialization. These
      proposals were evaluated in a short-term longitudinal study of 94 preschool-aged
      children. Parenting and basal RSA were measured at home, then 6-10 months later
      behavioral adjustment and RSA in lab baseline and socially challenging contexts
      were measured. Children with relatively higher RSA in social challenge than at
      baseline (DeltaRSA) had fewer internalizing problems (IP) and externalizing
      problems (EP), and better behavioral self-regulation (SR). Mothers who used more
      negative control had children with lower DeltaRSA, more IP and EP, and less SR.
      Structural equation modeling showed that vagal regulation mediated associations
      between maternal negative control and children's adjustment; maternal negative
      control did not predict EP or SR after accounting for DeltaRSA. Associations were
      consistent across boys and girls, with one exception: Higher DeltaRSA was
      significantly associated with fewer EP in boys only. These findings suggest that
      the practical significance of physiological regulation might be best revealed in
      ecologically valid procedures, and that children's physiological mechanisms of
      emotion regulation are shaped by their experiences of parental socialization.

PMID- 18722500
TI  - Electrophysiological and behavioral evidence of gender differences in the
      modulation of distraction by the emotional context.
AB  - Gender differences in brain activity while processing emotional stimuli have been
      demonstrated by neuroimaging and electrophysiological studies. However, the
      possible differential effects of emotion on attentional mechanisms between women
      and men are less understood. The present study aims to elucidate any gender
      differences in the modulation of unexpected auditory stimulus processing using an
      emotional context elicited by aversive images. Fourteen men and fourteen women
      performed a well-established auditory-visual distraction paradigm in which
      distraction was elicited by novel stimuli within a neutral or negative emotional
      context induced by images from the IAPS. Response time increased after unexpected
      novel sounds as a behavioral effect of distraction, and this increase was larger
      for women, but not for men, within the negative emotional context. Novelty-P3 was
      also modulated by the emotional context for women but not for men. These results
      reveal stronger novelty processing in women than in men during a threatening
      situation.

PMID- 18722501
TI  - Modes and cuts in metabolic networks: complexity and algorithms.
AB  - Constraint-based approaches recently brought new insight into our understanding
      of metabolism. By making very simple assumptions such as that the system is at
      steady-state and some reactions are irreversible, and without requiring kinetic
      parameters, general properties of the system can be derived. A central concept in
      this methodology is the notion of an elementary mode (EM for short) which
      represents a minimal functional subsystem. The computation of EMs still forms a
      limiting step in metabolic studies and several algorithms have been proposed to
      address this problem leading to increasingly faster methods. However, although a
      theoretical upper bound on the number of elementary modes that a network may
      possess has been established, surprisingly, the complexity of this problem has
      never been systematically studied. In this paper, we give a systematic overview
      of the complexity of optimisation problems related to modes. We first establish
      results regarding network consistency. Most consistency problems are easy, i.e.,
      they can be solved in polynomial time. We then establish the complexity of
      finding and counting elementary modes. We show in particular that finding one
      elementary mode is easy but that this task becomes hard when a specific EM (i.e.
      an EM containing some specified reactions) is sought. We then show that counting
      the number of elementary modes is musical sharpP-complete. We emphasize that the
      easy problems can be solved using currently existing software packages. We then
      analyse the complexity of a closely related task which is the computation of so
      called minimum reaction cut sets and we show that this problem is hard. We then
      present two positive results which both allow to avoid computing EMs as a prior
      to the computation of reaction cuts. The first one is a polynomial approximation
      algorithm for finding a minimum reaction cut set. The second one is a test for
      verifying whether a set of reactions constitutes a reaction cut; this test can be
      readily included in existing algorithms to improve their performance. Finally, we
      discuss the complexity of other cut-related problems.

PMID- 18722502
TI  - Simple example of structure versus property relationship applied to a reduced
      friction biosystem, a quite personal opinion.
AB  - Structure versus property (small-scale) relationship enters when something
      interesting is going to happen in a biosystem. This special-type "happening" is
      actually appearing to be manifested at both micro- and mesoscopic levels of
      always productive soft-matter organization under dynamic response, especially the
      one characteristic of the articular cartilage--an efficient, designed-by-nature
      multi-membrane, and virtually, with-ion-channels equipped, absorber and load
      relaxor.

PMID- 18722503
TI  - Editorial foreword to MCE special issue on "non-mammalian models of endocrine
      signalling".

PMID- 18722504
TI  - Adrenergic regulation of P2X3 and TRPV1 receptors: differential effects of spared
      nerve injury.
AB  - Local application of alphabetaMeATP (ligand for P2X3 receptors) and capsaicin
      (ligand for TRPV1 receptors) to the rat hindpaw produces pain behaviors
      (flinching) which are enhanced by noradrenaline (NA). In this study, we have
      examined the effect of nerve injury on adrenergic regulation of P2X3 and TRPV1
      receptors by administering alphabetaMeATP and capsaicin, alone and in combination
      with NA, into the lateral and medial hindpaw in the spared nerve injury (SNI)
      model; this allows for an exploration of the role of injured and uninjured
      afferents in their effects on nociceptive signaling using a behavioral model.
      Following lateral hindpaw injections (sural sensory field), effects of NA and
      alphabetaMeATP, both alone and in combination, were increased following SNI, but
      no such effects were seen following medial hindpaw injections (saphenous sensory
      field). Following lateral hindpaw injections, the effect of capsaicin alone was
      unaltered following SNI, but the effect of NA/capsaicin was reduced; this latter
      effect was not seen following medial hindpaw injections. At the lateral site,
      prazosin (alpha1-adrenergic receptor antagonist) inhibited the effect of
      NA/alphabetaMeATP following SNI, but neither prazosin nor GF109203X (protein
      kinase C inhibitor) inhibited the effect of NA/capsaicin following SNI. These
      results demonstrate: (a) an enhanced adrenergic regulation of P2X3 receptor
      activity at lateral sites following SNI where signaling afferents are directly
      influenced by injured neurons; (b) differential effects on adrenergic regulation
      of TRPV1 receptors under the same conditions; (c) lack of such changes when
      agents are administered into medial sites following SNI.

PMID- 18722505
TI  - Lack of light-induced elevation of renal sympathetic nerve activity and plasma
      corticosterone levels in PACAP-deficient mice.
AB  - PACAP is a neurotransmitter involved in the signal transduction of light
      stimulation in the suprachiasmatic nucleus (SCN). Light stimulation affects
      autonomic nerve activity via the SCN, and here we tested whether PACAP
      participates in light-induced regulation of sympatho-adrenal activity by using
      PACAP-deficient (Adcyap1(-/-)) mice. Light stimulation (100 lux, 30 min)
      significantly elevated both renal sympathetic nerve activity (RSNA), which was
      monitored on a digital oscilloscope, and plasma corticosterone levels in wild
      type mice, but both responses were almost abolished in Adcyap1(-/-) mice.
      Although light-induced c-Fos expression in the SCN was observed in both
      genotypes, the numbers of c-Fos positive cells were significantly decreased in
      Adcyap1(-/-) mice. These data suggest that PACAP signaling pathway is involved in
      light-induced stimulation of RSNA and plasma corticosterone release through SCN
      of brain.

PMID- 18722506
TI  - The formation of catechol isoquinolines in PC12 cells exposed to manganese.
AB  - Chronic exposure to manganese causes parkinsonian symptoms and has been
      implicated as an environmental factor in the pathogenesis of Parkinson's disease
      (PD). Here we show that manganese inhibits the proliferation of PC12 cells and
      induces apoptosis through the formation of catechol isoquinolines. Manganese
      induces the production of 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline
      (salsolinol, Sal) and N-methyl-salsolinol (NMSal) in PC12 cells, and increases
      the levels of malondialdehyde (MDA) in a dose-dependent manner. The data
      indicates that the formation of catechol isoquinolines due to oxidative stress
      induced by MnCl(2) may be a mechanism by which manganese causes degeneration of
      dopaminergic neurons.

PMID- 18722507
TI  - Potential protection of green tea polyphenols against ultraviolet irradiation
      induced injury on rat cortical neurons.
AB  - The present study was performed to investigate the possible protective effects of
      green tea polyphenols against ultraviolet (UV)-C light irradiation-induced cell
      death in the cultured rat cortical neurons. We found that UV-C light irradiation
      induced marked cell death tested by 3-(4,5-Dimethylthiazole-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) and TdT-mediated biotin-dUTP nicked-end labeling
      (TUNEL) assay. Protective effects of green tea polyphenols on UV-C light
      irradiation-induced apoptosis in cortical neurons were demonstrated by testing
      the content of Bax, which is involved in cell death. The expression of active Bax
      in cultured rat cortical neurons was inhibited significantly by green tea
      polyphenols compared to UV irradiation group tested by the immunoprecipitation
      assay and Western blot assay. However, there were no significant changes in the
      contents of total Bax after treatment with green tea polyphenols in UV-C light
      irradiated rat cortical neurons. Our results demonstrated that the green tea
      polyphenols inhibited the active Bax expression, suggesting a neuroprotective
      effect of green tea polyphenols against the UV-C light irradiation-induced injury
      on cortical neurons.

PMID- 18722508
TI  - Electrical stimulation modulates the amphetamine-induced hemodynamic changes: an
      fMRI study to compare the effect of stimulating locations and frequencies on
      rats.
AB  - Our previous fMRI and microdialysis measurements showed that electroacupuncture
      (EA) at LI4 was effective in alleviating excessive cerebral dopamine release
      induced by d-amphetamine (AMPH) in rats. We now compare the effect of EA in
      adjusting excess dopamine release at two stimulating frequencies (2 Hz versus 100
      Hz at LI4) and at two acupoints (forepaw (LI4) versus hindpaw (ST36), at 2 Hz).
      fMRI measurements of relative cerebral blood volume (rCBV) were used to monitor
      the brain activity of "rest", followed by AMPH challenge, 10 min "rest", and then
      20 min of EA. RESULTS: EA at LI4 and ST36 significantly attenuated the AMPH
      induced rCBV increases in the striatum, S1 cortex, and thalamus. Frequency: EA at
      100 Hz induced greater attenuation of rCBV than EA at 2 Hz in the S1, insula,
      anterior cingulate cortices, dorsolateral striatum, and thalamus. Acupoints: EA
      at LI4 modulated a broader area in the medial anterior striatum while EA at ST36
      modulated a more site-specific area in the dorsolateral striatum. In the
      thalamus, EA at LI4 showed greater attenuating effect than EA at ST36 did.
      However, in the insular cortex, EA at ST36 showed stronger attenuation.
      CONCLUSION: EA at both LI4 and ST36 was effective in restoring dopamine
      homeostasis from an excess state, with the most effective response at LI4 with
      100 Hz, while the responses to 2Hz EA at LI4 and ST36 showed slightly different
      spatial distribution of MR signal. This therefore provided insight into the
      neurophysiological basis of electroacupuncture effects in cortical and
      subcortical circuits.

PMID- 18722509
TI  - The intracellular domain of amyloid precursor protein induces neuron-specific
      apoptosis.
AB  - Although amyloid precursor protein (APP) has central roles in Alzheimer's
      disease, the physiological functions of this protein have yet to be fully
      elucidated. APP homologues show significant sequence conservation in the
      intracellular domain through evolution, which may reflect the functional
      importance of the intracellular domain of APP (AICD). To examine this
      possibility, we established embryonic carcinoma P19 cell lines overexpressing
      AICD. Although neurons could be differentiated from these cell lines with
      retinoic acid treatment, overexpression of AICD gave rise to neuron-specific cell
      death. Furthermore, DNA fragmentation was detected and TUNEL-positive cells were
      also Tuj1-positive neurons. Taken together, we concluded that AICD can induce
      neuron-specific apoptosis.

PMID- 18722511
TI  - Stroke-induced immunodepression and post-stroke infections: lessons from the
      preventive antibacterial therapy in stroke trial.
AB  - Infections are a leading cause of death in patients with acute CNS injury such as
      stroke. Recent experimental evidence indicated that stroke leads to suppression
      of innate and adaptive peripheral immune responses which predisposes to
      infection. However, less is known on phenotypic and functional immune alterations
      in correlation with the occurrence of infectious complications in patients with
      acute stroke. EXPERIMENTAL PROCEDURES: In the recently completed randomized,
      double blind, placebo-controlled Preventive Antibacterial Therapy in Stroke
      (PANTHERIS) trial on the efficacy of short-term antibacterial therapy to prevent
      the development of post-stroke infections, we assessed longitudinal changes in
      lymphocyte subpopulations and mitogen-induced lymphocytic interferon gamma (IFN)
      gamma production using flow cytometry in 80 patients with acute severe stroke at
      days 1, 3, 8, 90 and 180 after clinical onset. Plasma interleukin (IL)-6 and IL
      10 concentration as well as urinary levels of norepinephrine and cortisol was
      assessed within the first 8 days after stroke. Patients of the placebo and verum
      (moxifloxacin) treatment groups who did or did not develop infections within 11
      days after stroke were compared to identify immunological changes associated with
      the occurrence of post-stroke infections. RESULTS: Rapid T-lymphopenia and long
      lasting suppression of lymphocytic IFN-gamma production were observed in all
      stroke patients. Patients of the placebo group who developed infections showed a
      trend toward greater decline of CD4+ Th cell counts and higher urinary levels of
      norepinephrine early after stroke than patients without infections. Onset of
      infections was accompanied with higher plasma IL-6 levels in the placebo group
      but not in the moxifloxacin group. In addition, an early rise in plasma IL-10 was
      detected in patients who developed infections despite preventive antibacterial
      treatment. CONCLUSION: A rapid loss and functional deactivation of T cells are
      common changes in stroke patients consistent with immunodepression after brain
      ischemia. A stronger decrease in cellular immune responses and an increased
      sympathetic activity after stroke are associated with a higher risk of
      infections. Increased plasma levels of the anti-inflammatory cytokine IL-10 early
      after stroke may identify patients who will not respond to preventive
      antibacterial therapy with moxifloxacin.

PMID- 18722510
TI  - Sweat gland innervation is pioneered by sympathetic neurons expressing a
      cholinergic/noradrenergic co-phenotype in the mouse.
AB  - Classic neurotransmitter phenotypes are generally predetermined and develop as a
      consequence of target-independent lineage decisions. A unique mode of target
      dependent phenotype instruction is the acquisition of the cholinergic phenotype
      in the peripheral sympathetic nervous system. A body of work suggests that the
      sweat gland plays an important role to determine the cholinergic phenotype at
      this target site. A key issue is whether neurons destined to innervate the sweat
      glands express cholinergic markers before or only after their terminals make
      target contact. We employed cholinergic-specific over-expression of the vesicular
      acetylcholine transporter (VAChT) in transgenic mice to overcome sensitivity
      limits in the detection of initial cholinergic sweat gland innervation. We found
      that VAChT immunoreactive nerve terminals were present around the sweat gland
      anlage already from the earliest postnatal stages on, coincident selectively at
      this sympathetic target with tyrosine hydroxylase-positive fibers. Our results
      provide a new mechanistic model for sympathetic neuron-target interaction during
      development, with initial selection by the target of pioneering nerve terminals
      expressing a cholinergic phenotype, and subsequent stabilization of this
      phenotype during development.

PMID- 18722512
TI  - Levodopa-sensitive, dynamic changes in effective connectivity during simultaneous
      movements in Parkinson's disease.
AB  - Changes in effective connectivity during the performance of a motor task appear
      important for the pathogenesis of motor symptoms in Parkinson's disease (PD). One
      type of task that is typically difficult for individuals with PD is simultaneous
      or bimanual movement, and here we investigate the changes in effective
      connectivity as a potential mechanism. Eight PD subjects off and on l-DOPA
      medication and 10 age-matched healthy control subjects performed both
      simultaneous and unimanual motor tasks in an fMRI scanner. Changes in effective
      connectivity between regions of interest (ROIs) during simultaneous and unimanual
      task performance were determined with structural equation modeling (SEM), and
      changes in the temporal dynamics of task performance were determined with
      multivariate autoregressive modeling (MAR). PD subjects demonstrated alterations
      in both effective connectivity and temporal dynamics compared with control
      subjects during the performance of a simultaneous task. l-DOPA treatment was able
      to partially normalize effective connectivity and temporal patterns of activity
      in PD, although some connections remained altered in PD even after medication.
      Our results suggest that difficulty performing simultaneous movements in PD is at
      least in part mediated by a disruption of effective communication between
      widespread cortical and subcortical areas, and l-DOPA assists in normalizing this
      disruption. These results suggest that even when the site of neurodegeneration is
      relatively localized, study of how disruption in a single region affects
      connectivity throughout the brain can lead to important advances in the
      understanding of the functional deficits caused by neurodegenerative disease.

PMID- 18722513
TI  - A specific role for group II metabotropic glutamate receptors in hippocampal long
      term depression and spatial memory.
AB  - Activity-dependent and sustained alterations in synaptic efficacy are widely
      regarded as the cellular correlates underlying learning and memory. Metabotropic
      glutamate receptors (mGluRs) are intrinsically involved in both hippocampal
      synaptic plasticity and spatial learning. Group II mGluRs are required for
      persistent hippocampal long-term depression (LTD), but are not required for long
      term potentiation (LTP) in the hippocampal CA1 region in vivo. The role of these
      receptors in spatial learning, and in synaptic plasticity in the dentate gyrus in
      vivo has not yet been the subject of close scrutiny. We investigated the effects
      of group II mGluR antagonism on LTP and LTD in the adult rat, at medial perforant
      path-dentate gyrus synapses, and on spatial learning in the eight-arm radial
      maze. Daily application of the group 2 mGluR antagonist (2S)-alpha-ethylglutamic
      acid (EGLU) resulted in impairment of long-term (reference) memory with effects
      becoming apparent 6 days after training and drug-treatment began. Short-term
      (working) memory was unaffected throughout the 10-day study. Acute injection of
      EGLU did not affect either LTD or LTP in the dentate gyrus in vivo. Following six
      daily applications of EGLU a clear impairment of LTD but not LTP was apparent
      however. These data support that prolonged antagonism of group II mGluRs results
      in an impairment of LTD that parallels the appearance of spatial memory deficits
      arising from group II mGluR antagonism. These findings support the importance of
      group II mGluRs for spatial memory formation and offer a further link between LTD
      and the encoding of spatial information in the hippocampus.

PMID- 18722514
TI  - Housekeeping genes revisited: different expressions depending on gender, brain
      area and stressor.
AB  - Housekeeping gene (HKG) mRNAs are used to normalize expression data of genes of
      interest in quantitative reverse transcriptase polymerase chain reaction studies.
      Such normalization assumes constant HKG gene expression under all circumstances.
      Although sporadic evidence suggests that HKG expression may not always fulfill
      this requirement and, therefore, such normalization may lead readily to erroneous
      results, this fact is generally not sufficiently appreciated by investigators.
      Here, we have systematically analyzed the expression of three common HKGs,
      glyceraldehyde-3-phosphate dehydrogenase, ribosomal subunit 18S and beta-actin,
      in two different stress paradigms, in various brain areas, in male and in female
      rats. HKG expressions differed considerably with respect to brain area, type of
      stressor and gender, in an HKG-specific manner. Therefore, we conclude that
      before final experimentation, pilot expression studies are necessary to select an
      HKG which expression is unaffected by the experimental factor(s), allowing
      reliable interpretation of expression data of genes of interest.

PMID- 18722515
TI  - Effects of chronic treatment with levetiracetam on hippocampal field responses
      after pilocarpine-induced status epilepticus in rats.
AB  - Levetiracetam (Keppra) is a new generation antiepileptic drug characterized by a
      unique profile of activity in experimental models of epilepsy. It also has a
      distinct binding site in the brain, i.e. the synaptic vesicle protein type 2
      (SV2A). Levetiracetam has been reported to have antiepileptogenic and disease
      modifying properties. In the present study the effects of chronic treatment with
      levetiracetam were assessed in rats that sustained pilocarpine-induced status
      epilepticus (SE). Hippocampal field potentials were recorded in vivo in
      anesthetized animals after 3-day washout period that followed 21-day treatment
      with different doses of levetiracetam (50, 150 or 300 mg/kg/day) administered via
      ALZET osmotic mini-pumps. Vehicle treated rats together with naive animals (not
      subjected to SE) were used as control groups. Chronic treatment with
      levetiracetam yielded clinically relevant plasma concentrations throughout the
      experiment with complete washout of the drug 3 days after treatment cessation. At
      this point in time post-SE rats chronically treated with vehicle developed clear
      signs of hippocampal hyperexcitability, i.e. increased amplitude of population
      spike (PS) recorded in the dentate gyrus and reduced paired-pulse inhibition in
      the CA1 area. Levetiracetam treatment dose-dependently counteracted these long
      term effects of pilocarpine-induced SE. Furthermore, at the dose of 300 mg/kg/day
      levetiracetam restored these parameters back to control level. The present
      results indicate that chronic treatment with levetiracetam completely inhibits
      the development of hippocampal hyperexcitability following pilocarpine-induced
      SE.

PMID- 18722516
TI  - Auditory stimuli enhance MDMA-conditioned reward and MDMA-induced nucleus
      accumbens dopamine, serotonin and locomotor responses.
AB  - MDMA (3,4-methylenedioxymethamphetamine), also known as ecstasy, is a popular
      drug often taken in environments rich in audio and visual stimulation, such as
      clubs and dance parties. The present experiments were conducted to test the
      notion that auditory stimulation influences the rewarding effects of MDMA. In
      Experiment 1, a conditioned place preference (CPP) procedure was conducted in
      which rats received MDMA (1.5mg/kg, s.c.) in a distinctive environment
      accompanied by music (65-75dB), white noise (70dB), or no added sound. Animals
      were pretreated with saline on alternating days in an alternate environment.
      Results revealed CPP in animals exposed to white noise during MDMA trials. For
      Experiment 2, rats from Experiment 1 had access to operant levers that delivered
      intravenous MDMA (0.5mg/kg/inj) or saline (0.1ml) on alternate days in the
      presence or absence of the same types of auditory stimuli as previously
      experienced. After three each of MDMA and non-reinforced (saline) sessions,
      animals were tested for NAcc DA and 5-HT responses to MDMA (1.5mg/kg) or saline
      under the same stimulus conditions. Findings revealed that NAcc DA and 5-HT
      increased after an MDMA injection, and both DA and 5-HT were significantly
      highest in animals exposed to music during the test session. These results
      indicate that paired sensorial stimuli can engage the same systems activated
      during drug use and enhance neurochemical and behavioral responses to MDMA
      administration.

PMID- 18722517
TI  - Executive functions with different motor outputs in somatosensory Go/Nogo tasks:
      an event-related functional MRI study.
AB  - The aim of this event-related functional magnetic resonance imaging (fMRI) study
      was to investigate and compare executive functions with different motor outputs
      in somatosensory Go/Nogo tasks: (1) Button press and (2) Count. Go and Nogo
      stimuli were presented with an even probability. We observed a common network for
      Movement and Count Go trials in several regions of the brain including the
      dorsolateral (DLPFC) and ventrolateral prefrontal cortices (VLPFC), supplementary
      motor area (SMA), posterior parietal cortex (PPC), inferior parietal lobule
      (IPL), Insula, and superior temporal gyrus (STG). Direct comparison revealed that
      primary sensorimotor area (SMI), premotor area (PM), and anterior cingulate
      cortex (ACC) were more activated during Movement than Count Go trials. In
      contrast, the VLPFC was more activated during Count than Movement Go trials. Our
      results suggest that there were two neural networks for the supramodal executive
      function, common and uncommon, depending on the required response mode.

PMID- 18722518
TI  - Novel wound models for characterizing ibuprofen release from foam dressings.
AB  - The purpose of the present study was to design and characterize low exudate level
      wound (LEW) and high exudate level wound (HEW) in vitro models by means of
      investigating therapeutic substance release from exudate-absorbing formulations.
      Biatain Ibu foam dressing was used to characterize in vitro release of ibuprofen
      within the models and also for in vitro-in vivo correlation (IVIVC) studies.
      Ibuprofen release was described by zero order rate constants of 0.0147 for 1 day
      and 0.0038 mg/cm(2) h for 3 days in HEW and LEW models, respectively. The release
      is suggested to be controlled by ibuprofen diffusion from the dressing in the HEW
      model, whereas fluid absorption is rate-limiting in the LEW model. Ibuprofen
      release, from Biatain Ibu foam dressings in vivo, is within the same ranges as in
      vitro. Thus, it is suggested that, depending on the level of exudate, the in vivo
      release of ibuprofen depends on ibuprofen diffusion from and absorption of
      exudates to the dressings. Consequently, both the HEW and LEW in vitro models
      should be applied in order to fully characterize ibuprofen release from Biatain
      Ibu foam dressings. Future studies may show whether these in vitro models can be
      used to characterize therapeutic substance release from exudate-absorbing
      formulations in general.

PMID- 18722520
TI  - Duplication of phospholipase C-delta gene family in fish genomes.
AB  - Fishes possess more genes than other vertebrates, possibly because of a genome
      duplication event during the evolution of the teleost (ray-finned) fish lineage.
      To further explore this idea, we cloned five genes encoding phosphoinositide
      specific phospholipase C-delta (PLC-delta), designated respectively PoPLC-deltas,
      from olive flounder (Paralichthys olivaceus), and we performed phylogenetic
      analysis and sequence comparison to compare our putative gene products (PoPLC
      deltas) with the sequences of known human PLC isoforms. The deduced amino acid
      sequences shared high sequence identity with human PLC-delta1, -delta3, and 
      delta4 isozymes and exhibited similar primary structures. In phylogenetic
      analysis of PoPLC-deltas with PLC-deltas of five teleost fishes (zebrafish,
      stickleback, medaka, Tetraodon, and Takifugu), three tetrapods (human, chicken,
      and frog), and two tunicates (sea squirt and pacific sea squirt), whose putative
      sequences of PLC-delta are available in Ensembl genome browser, the result also
      indicated that the two paralogous genes corresponding to each PLC-delta isoform
      originated from fish-specific genome duplication prior to the divergence of
      teleost fish. Our analyses suggest that an ancestral PLC-delta gene underwent
      three rounds of genome duplication during the evolution of vertebrates, leading
      to the six genes of three PLC-delta isoforms in teleost fish.

PMID- 18722519
TI  - Pathway analysis of seven common diseases assessed by genome-wide association.
AB  - Recent genome-wide association studies (GWAS) have identified DNA sequence
      variations that exhibit unequivocal statistical associations with many common
      chronic diseases. However, the vast majority of these studies identified
      variations that explain only a very small fraction of disease burden in the
      population at large, suggesting that other factors, such as multiple rare or low
      penetrance variations and interacting environmental factors, are major
      contributors to disease susceptibility. Identifying multiple low-penetrance
      variations (or "polygenes") contributing to disease susceptibility will be
      difficult. We present a pathway analysis approach to characterizing the likely
      polygenic basis of seven common diseases using the Wellcome Trust Case Control
      Consortium (WTCCC) GWAS results. We identify numerous pathways implicated in
      disease predisposition that would have not been revealed using standard single
      locus GWAS statistical analysis criteria. Many of these pathways have long been
      assumed to contain polymorphic genes that lead to disease predisposition.
      Additionally, we analyze the genetic relationships between the seven diseases,
      and based upon similarities with respect to the associated genes and pathways
      affected in each, propose a new way of categorizing the diseases.

PMID- 18722521
TI  - Lipopolysaccharide produces dose-dependent reductions of the acoustic startle
      response without impairing prepulse inhibition in male rats.
AB  - This study examined the dose-dependent effects of Lipopolysaccharide (LPS) on the
      acoustic startle response and prepulse inhibition (PPI) in male Long-Evans rats.
      LPS is known to stimulate the innate immune system and result in behavior
      modifications referred to as "sickness behaviors". The purpose of this study was
      to assess the ability of LPS to modulate sensorimotor reflexes (Startle-Only
      trials) and/or sensory processing (PPI trials). Rats were injected
      intraperitoneally with LPS (50, 100 or 200 microg/kg LPS, n=9/group) or saline
      vehicle (n=14) on 2 test days 72 h apart. Subjects were placed in a familiar
      startle box apparatus where startle response magnitudes were recorded following
      115 dB Startle-Only trials and PPI trials (with prepulses at +3, +6 and +12 dB
      above background noise). Analysis of Startle-Only trials indicated a significant
      dose-dependent effect of LPS on Test Day 1. The 200 microg/kg LPS group exhibited
      significantly reduced startle response magnitude relative to all other
      treatments. On the PPI trials no LPS groups displayed significantly different
      performance from vehicle controls. Also, DayxDrug interactions for both Startle
      Only and PPI trial types indicated behavioral tolerance to LPS. LPS reduced the
      acoustic startle response in a dose-dependent manner on Test Day 1. From the PPI
      data, it is evident that all treatment groups elicited near-normal inhibition
      levels indicating adequate sensory function. In combination, the results suggest
      that the range of sickness behaviors following LPS-administration to adult rats
      includes decreased non-voluntary motor activity as reflected by reduced startle
      magnitude.

PMID- 18722522
TI  - Maternally transmitted milk containing recombinant human catalase provides
      protection against oxidation for mouse offspring during lactation.
AB  - Catalase plays an important role in protecting organisms against oxidative damage
      caused by reactive oxygen species (ROS) by degrading surplus hydrogen peroxide.
      Addition of exogenous catalase can alleviate injuries caused by ROS. Thus,
      production of human catalase through genetic engineering will meet the increasing
      therapeutic demand for this enzyme. In this study, we successfully expressed the
      recombinant gene in mouse mammary gland, and biologically active human catalase
      was secreted into the milk of the transgenic mice. The peroxisomal targeting
      sequence (PTS) within the catalase gene had no significant negative effect on the
      secretion of the recombinant protein. Intake of the transgenic milk by the pups
      was found to decrease lipid peroxidation, increase the total superoxide dismutase
      (T-SOD) activity in the brain, and enhance the total antioxidative capacity (T
      AOC) of brain, liver, and serum. To our knowledge, this is the first example of
      efficient production of biologically active human catalase in the milk of
      transgenic animals. Our study suggests that scaled-up production in transgenic
      farm animals would yield sufficient human catalase for biomedical research and
      clinical therapies.

PMID- 18722523
TI  - Systemic administration of PEP-1-SOD1 fusion protein improves functional recovery
      by inhibition of neuronal cell death after spinal cord injury.
AB  - Spinal cord injury (SCI) produces excessive levels of reactive oxygen species
      (ROS) that induce apoptosis of neurons. Cu,Zn-superoxide dismutase (SOD1) is a
      key antioxidant enzyme that detoxifies intracellular ROS, thereby protecting
      cells from oxidative damage. PEP-1 is a peptide carrier capable of delivering
      full-length native peptides or proteins into cells. In the study described here,
      we fused a human SOD1 gene with PEP-1 in a bacterial expression vector to produce
      a genetic in-frame PEP-1-SOD1 fusion protein; we then investigated the
      neuroprotective effect of the fusion protein after SCI. The expressed and
      purified PEP-1-SOD1 was efficiently delivered into cultured cells and spinal
      cords in vivo, and the delivered fusion protein was biologically active. Systemic
      administration of PEP-1-SOD1 significantly decreased levels of ROS and protein
      carbonylation and nitration in spinal motor neurons after injury. PEP-1-SOD1
      treatment also significantly inhibited mitochondrial cytochrome c release and
      activation of caspase-9 and caspase-3 in spinal cords after injury. Furthermore,
      PEP-1-SOD1 treatment significantly reduced ROS-induced apoptosis of motor neurons
      and improved functional recovery after SCI. These results suggest that PEP-1-SOD1
      may provide a novel strategy for the therapeutic delivery of antioxidant enzymes
      that protect neurons from ROS after SCI.

PMID- 18722524
TI  - Molecular detection and phylogenetic characterization of Gordonia species in
      heavily oil-contaminated soils.
AB  - This study was undertaken to assess genetic diversity among Gordonia species
      present in heavily oil-contaminated sites using both a culture-dependent and a
      culture-independent (PCR-denaturing gradient gel electrophoresis (DGGE))
      approach. Soil samples for this purpose were collected from 8 different heavily
      (crude) oil-contaminated industrial park sites located around Kaohsiung County,
      Taiwan. Using Gordonia-specific PCR-DGGE, a significant increase in Gordonia
      species diversity was noted in 1% heavily oil-enriched soil. A total of 67
      strains were scored and identified as Gordonia after genus-specific PCR
      amplification and sequencing. BOX-PCR fingerprinting of culturable Gordonia
      showed wide strain diversity. A total of 33 different strains were identified
      from most of the sampling sites. Based on gyrB gene sequence analysis, all
      Gordonia strains could be segregated into five major clusters. Gordonia amicalis
      was the predominant species in all oil-amended soil samples. Isolates sharing
      <98.5% gyrB gene sequence similarities with Gordonia type strains represent
      indigenous novel Gordonia species. Variations in phenotypic characteristics
      further confirm the presence of a wide range of species and strain diversity
      among Gordonia isolates. Based on the genotypic and phenotypic details obtained
      here, we conclude that heavily oil-contaminated soil supports diverse indigenous
      Gordonia strains.

PMID- 18722525
TI  - Modulating Notch signaling by pathway-intrinsic and pathway-extrinsic mechanisms.
AB  - Despite a relatively simple core-signaling transduction machinery, Notch
      signaling controls cell differentiation in many different tissues and at multiple
      stages in a given cell lineage. To understand how Notch generates this multitude
      of cellular responses, it is important to learn how the Notch-signaling output is
      modulated at various levels. Pathway-intrinsic as well as pathway-extrinsic
      mechanisms, including cross-talk between Notch and other major signaling
      mechanisms, modulate Notch signaling, contributing to the versatile output. In
      this review, we discuss how Notch signaling is altered in tumors and illustrate
      the complexity in signaling pathway cross-talk with examples of how Notch
      synergizes with NF-kappaB signaling and the cellular response to lowered oxygen
      (hypoxia).

PMID- 18722526
TI  - Context dependence of proneural bHLH proteins.
AB  - A key point in neural development is the commitment of progenitor cells to a
      specific neural fate. In all animals studied, proneural proteins - transcription
      factors of the basic helix-loop-helix (bHLH) family - are central to this
      process. The function of these factors is strongly influenced by the spatial and
      temporal context in which they are expressed. It is important to understand the
      molecular mechanisms by which developmental context interacts with and modifies
      the intrinsic functions and properties of the proneural proteins. Recent insights
      have been obtained in Drosophila and vertebrates from analysis of how bHLH
      proteins interact with other transcription factors to regulate target genes.

PMID- 18722527
TI  - Transgene expression and silencing in a tick cell line: A model system for
      functional tick genomics.
AB  - The genome project of the black legged tick, Ixodes scapularis, provides sequence
      data for testing gene function and regulation in this important pathogen vector.
      We tested Sleeping Beauty (SB), a Tc1/mariner group transposable element, and
      cationic lipid-based transfection reagents for delivery and genomic integration
      of transgenes into I. scapularis cell line ISE6. Plasmid DNA and dsRNA were
      effectively transfected into ISE6 cells and they were successfully transformed to
      express a red fluorescent protein (DsRed2) and a selectable marker, neomycin
      phosphotransferase (NEO). Frequency of transformation was estimated as 1
      transformant per 5000-10,000 cells and cultures were incubated for 2-3 months in
      medium containing the neomycin analog G418 in order to isolate transformants.
      Genomic integration of the DsRed2 transgene was confirmed by inverse PCR and
      sequencing that demonstrated a TA nucleotide pair inserted between SB
      inverted/direct repeat sequences and tick genomic sequences, indicating that
      insertion of the DsRed2 gene into the tick cell genome occurred through the
      activity of SB transposase. RNAi using dsRNA transcribed from the DsRed2 gene
      silenced expression of red fluorescent protein in transformed ISE6 cells. SB
      transposition in cell line ISE6 provides an effective means to explore the
      functional genomics of I. scapularis.

PMID- 18722528
TI  - Role of caspases, calpain and cdk5 in ammonia-induced cell death in developing
      brain cells.
AB  - Hyperammonemia in neonates and infants causes irreversible damages in the
      developing CNS due to brain cell loss. Elucidating the mechanisms triggering
      ammonia-induced cell death in CNS is necessary for the development of
      neuroprotective strategies. We used reaggregated developing brain cell cultures
      derived from fetal rat telencephalon exposed to ammonia as an experimental model.
      Ammonia induced neuronal and oligodendroglial death, triggered apoptosis and
      activated caspases and calpain. Probably due to calpain activation, ammonia
      caused the cleavage of the cyclin-dependent kinase 5 activator, p35, to p25, the
      cdk5/p25 complex being known to lead to neurodegeneration. Roscovitine, a cdk5
      inhibitor, protected neurons from ammonia-induced cell death. However,
      roscovitine also impaired axonal growth, probably through inhibition of the
      remaining cdk5/p35 activity, which is involved in neurite outgrowth. Thus, cdk5
      appears as a promising therapeutic target for treating hyperammonemic newborns
      and infants, especially if one develops specific cdk5/p25 inhibitors.

PMID- 18722529
TI  - Entacapone potentiates the long-duration response but does not normalize levodopa
      induced molecular changes.
AB  - Coadministration of entacapone with levodopa attenuates motor complications in
      experimental models of Parkinson's disease. The mechanisms underlying entacapone
      effects are unknown. We investigated the effect of entacapone, on: long-duration
      response (LDR) to levodopa, levodopa-induced postsynaptic pharmacodynamic
      mechanisms and molecular changes in hemiparkinsonian rats. 6-Hydroxydopamine
      unilaterally lesioned rats were treated with levodopa (25 mg/kg)+vehicle;
      levodopa+entacapone (30 mg/kg) or saline, twice daily for 22 days. The LDR and
      the apomorphine-induced rotations were measured. In situ hybridization was
      performed measuring the expression of striatal preproenkephalin, preprodynorphin
      and dopamine D-3 receptor mRNAs, subthalamic cytochrome oxidase mRNA and nigral
      glutamic acid decarboxylase mRNA. Entacapone potentiated the LDR but did not
      modify either the apomorphine-induced rotational behavior or the molecular
      changes. Our results suggest that the effects of entacapone on levodopa-induced
      motor response are not mediated by postsynaptic mechanisms and that
      administration of entacapone is not able to normalize the molecular alterations
      induced by levodopa in the basal ganglia.

PMID- 18722530
TI  - Endothelial progenitor cells in vascular repair and remodeling.
AB  - Postnatal bone marrow contains a subtype of unique progenitor cells that have the
      capacity to differentiate into functional endothelial cells. Hence, these cells
      have been termed endothelial progenitor cells (EPCs). In general, circulating
      EPCs were characterized by the expression of CD133, CD34 and the vascular
      endothelial growth factor receptor-2 (VEGFR2). Recent data have additionally
      described some CD14(+/low) myeloid subsets as functional endothelial precursors.
      Convincing evidence in vivo has further emerged that the vascular homing of EPCs
      contributes to endothelial regeneration thereby limiting neointimal hyperplasia
      after arterial injury. However, in the context of primary atherosclerosis, plaque
      progression and destabilization, injection of EPCs as well as application of stem
      cell mobilizing factors have been shown to correlate with conversion to unstable
      plaque phenotype. Clinically, the number and function of EPCs have been
      positively linked with an improved endothelial function or regeneration but
      frequently inversely correlated with cardiovascular risk (factors). Thus,
      considering the dual contribution of EPCs in vascular repair and remodeling in
      primary atherosclerosis versus arterial injury and identifying mechanisms for
      selective control of their recruitment appears crucial to improve prediction and
      to directly modulate endogenous vascular homeostasis.

PMID- 18722531
TI  - Targeting adenoviral transgene expression to neurons.
AB  - Adenovirus (Ad) is an efficient and safe vector for CNS gene delivery since it
      infects non-replicating neurons and does not cause insertional mutagenesis of
      host cell genomes. However, the promiscuous Ad CAR receptor targets cells non
      specifically and activates a host immune response. Using Ad5 containing an
      expression cassette encoding the gene for green fluorescent protein, gfp,
      regulated by the neuron specific promoter synapsin-1 and the woodchuck post
      transcriptional regulatory element (WPRE), we demonstrate efficient, prolonged
      and promoter-restricted gfp expression in neurons of mixed primary adult rat
      dorsal root ganglion (DRG) and retinal cell cultures. We also demonstrate
      restricted gfp expression in DRG neurons after direct injections of Ad5
      containing the synapsin-1(gfp)/WPRE construct into L4 DRG in vivo, while Ad5
      CMV(gfp) transfected both DRG glia and neurons. Moreover, since the effective
      titres of delivered Ad5 are reduced with this neuron specific promoter/WPRE
      expression cassette, the viral immune challenge should be attenuated when used in
      vivo.

PMID- 18722532
TI  - Isoform-specific contribution of protein kinase C to prion processing.
AB  - The cellular prion protein (PrP(c)) undergoes a physiological cleavage between
      amino acids 111 and 112, thereby leading to the secretion of an amino-terminal
      fragment referred to as N1. This proteolytic event is either constitutive or
      regulated by protein kinase C (PKC) and is operated by the disintegrins
      ADAM9/ADAM10 or ADAM17 respectively. We recently showed that the stimulation of
      the M1/M3 muscarinic receptors potentiates this cleavage via the phosphorylation
      and activation of ADAM17. We have examined the contribution of various PKC
      isoforms in the regulated processing of PrP(c). First we show that the PDBu- and
      carbachol-stimulated N1 secretions are blocked by the general PKC inhibitor
      GF109203X. We establish that HEK293 and human-derived rhabdhomyosarcoma cells
      over-expressing constitutively active PKCalpha, PKCdelta or PKCepsilon, but not
      PKCzeta, produce increased amounts of N1 and harbor enhanced ability to hydrolyze
      the fluorimetric substrate of ADAM17, JMV2770. Conversely, over-expression of the
      corresponding dominant negative proteins abolishes PDBU-stimulated N1 secretion
      and restores N1 to levels comparable to constitutive production. Moreover,
      deletion of PKCalpha lowers N1 recovery in primary cultured fibroblasts.
      Importantly, mutation of threonine 735 of ADAM17 significantly lowers the PDBu
      induced N1 formation while transient over-expression of constitutively active
      PKCalpha, PKCdelta or PKCepsilon, but not PKCzeta, induced both the
      phosphorylation of ADAM17 on its threonine residues and N1 secretion. As a
      corollary, T735A mutation concomitantly reversed PKCalpha-, PKCdelta- and
      PKCepsilon-induced ADAM17 phosphorylation and N1 recovery. Finally, we
      established that PKCepsilon-dependent N1 production is fully prevented by ADAM17
      deficiency. Altogether, the present results provide strong evidence that the
      activation of PKCalpha, delta and epsilon, but not zeta, isoforms leads to
      increased N1 secretion via the phosphorylation and activation of ADAM17, a
      process that likely accounts for M1/M3 muscarinic receptors-mediated control of
      N1 production.

PMID- 18722533
TI  - Connectivity from the ventral anterior cingulate to the amygdala is modulated by
      appetitive motivation in response to facial signals of aggression.
AB  - For some people facial expressions of aggression are intimidating, for others
      they are perceived as provocative, evoking an aggressive response. Identifying
      the key neurobiological factors that underlie this variation is fundamental to
      our understanding of aggressive behaviour. The amygdala and the ventral anterior
      cingulate cortex (ACC) have been implicated in aggression. Using functional
      magnetic resonance imaging (fMRI), we studied how the interaction between these
      regions is influenced by the drive to obtain reward (reward-drive or appetitive
      motivation), a personality trait consistently associated with aggression. Two
      distinct techniques showed that the connectivity between the ventral ACC and the
      amygdala was strongly correlated with personality, with high reward-drive
      participants displaying reduced negative connectivity. Furthermore, the direction
      of this effect was restricted from ventral ACC to the amygdala but not vice
      versa. The personality-mediated variation in the pathway from the ventral
      anterior cingulate cortex to the amygdala provides an account of why signals of
      aggression are interpreted as provocative by some individuals more than others.

PMID- 18722534
TI  - In vivo labeling of adult neural progenitors for MRI with micron sized particles
      of iron oxide: quantification of labeled cell phenotype.
AB  - The subventricular zone (SVZ) is a continual source of neural progenitors
      throughout adulthood. Many of the animal models designed to study the migration
      of these cells from the ventricle to places of interest like the olfactory bulb
      or an injury site require histology to localize precursor cells. Here, it is
      demonstrated that up to 30% of the neural progenitors that migrate along the
      rostral migratory stream (RMS) in an adult rodent can be labeled for MRI via
      intraventricular injection of micron sized particles of iron oxide (MPIOs). The
      precursors migrating from the SVZ along the RMS were found to populate the
      olfactory bulb with all three types of neural cells; neurons, oligodendrocytes,
      and astrocytes. In all cases 10-30% of these cells were labeled in the RMS en
      route to the olfactory bulb. Ara-C, an anti-mitotic agent, eliminated precursor
      cells at the SVZ, RMS, and olfactory bulb and also eliminated the MRI detection
      of the precursors. This indicates that the MRI signal detected is due to
      progenitor cells that leave the SVZ and is not due to non-specific diffusion of
      MPIOs. Using MRI to visualize neural progenitor cell behavior in individual
      animals during plasticity or disease models should be a useful tool, especially
      in combination with other information that MRI can supply.

PMID- 18722535
TI  - Spatial dissociation of changes of level and signal-to-noise ratio in auditory
      cortex for tones in noise.
AB  - Functional magnetic resonance imaging has been used to investigate the signal
      representation in human auditory cortex for a sinusoidal signal in the presence
      of a noise masker. This paradigm is widely used in auditory research to study
      auditory processing. Five-note tonal melodies were presented in a masking noise
      for signal-to-noise ratios (S/N) from -18 dB to+24 dB in 6 dB-steps. For small
      S/N (-18 dB, -12 dB, -6 dB) the overall level of the sound is nearly constant,
      but the audibility of the tone varies with S/N. For S/N of 0 dB and above, the
      tone is always clearly audible, and the perceived change is mainly the increase
      in overall level. This interaction between S/N, overall level and perception is
      reflected by a spatial dissociation of the respective activation in auditory
      cortex. Brain regions mainly sensitive to level changes were found in various
      parts of the superior temporal lobes, including primary auditory cortex and
      Planum temporale, while those regions mainly sensitive to S/N changes were
      located at or close to lateral Heschl's gyrus. The overlap between these two
      regions is small. The results are interpreted as indicating that the coding of
      overall level and, thus, loudness is different from the coding of audibility of a
      periodic signal. The S/N-sensitive region largely overlaps with the pitch
      sensitive regions in lateral Heschl's gyrus found in previous studies. The
      results from the present study further suggest that the audibility of a tone in
      noise is related to the overall pitch strength.

PMID- 18722536
TI  - Detection of inter-hemispheric metabolic asymmetries in FDG-PET images using
      prior anatomical information.
AB  - [(18)F] FDG positron emission tomography (PET) is commonly used to highlight
      brain regions with abnormal metabolism. Correct interpretation of FDG images is
      important for investigation of diseases. When the FDG uptake is compared between
      hemispheres, confusion can arise because it might be difficult to determine
      whether an observed asymmetry is physiological and due to normal anatomical
      variation or pathological. In this paper we propose a new method, which
      calculates an anatomy-corrected asymmetry index (ACAI), to highlight inter
      hemispheric metabolic asymmetry in FDG images without the influence of anatomical
      asymmetry. Using prior anatomical information from MRI, the ACAI method only
      takes into account voxels that belong to a certain anatomical class. For the
      evaluation of detection performance, this method is applied on homogeneous brain
      phantoms and realistic analytical simulated FDG-PET images with known
      asymmetries. Results from these simulations demonstrated the validity of ACAI and
      its potential perspective in the future.

PMID- 18722537
TI  - Measurement of brain atrophy in subcortical vascular disease: a comparison of
      different approaches and the impact of ischaemic lesions.
AB  - Measurement of brain atrophy has been proposed as a surrogate marker in MS and
      degenerative dementias. Although cerebral small vessel disease predominantly
      affects white and subcortical grey matter, recent data suggest that whole brain
      atrophy is also a good indicator of clinical and cognitive status in this
      disease. Automated methods to measure atrophy are available that are accurate and
      reproducible in disease-free brains. However, optimal methods in small vessel
      disease have not been established and the impact of ischaemic lesions on
      different techniques has not been explored systematically. In this study, three
      contrasting techniques -- Statistical Parametric Mapping 5 (SPM5), SIENAX and
      BrainVisa -- were applied to measure cross-sectional atrophy (brain parenchymal
      fraction or BPF) in a large (n=143) two-centre cohort of patients with CADASIL, a
      genetic model of small vessel disease. All three techniques showed similar
      sensitivity to trends in BPF associated with age and lesion load. No single
      technique was particularly vulnerable to error as a result of lesions. Provided
      major errors in registration were excluded by visual inspection, manual
      correction of segmentations had a negligible impact with mean errors of 0.41% for
      SIENAX and 0.46% for BrainVisa. BPF correlated strongly with global cognitive
      function and physical disability, independent of the technique used. Correlation
      coefficients with the Minimental State Examination score were: BrainVisa 0.58,
      SIENAX 0.58, SPM5 0.60 (for all, p<0.001). These results suggest that all three
      methods can be applied reliably in patients with ischaemic lesions. Choice of
      analysis approach for this kind of clinical question will be determined by
      factors other than their robustness and precision, such as a desire to explore
      subtle localised changes using extensions of these processing tools.

PMID- 18722539
TI  - Phylogeny and biogeographic diversification of Maianthemum (Ruscaceae:
      Polygonatae).
AB  - Maianthemum (Ruscaceae) comprises 28-38 species and includes the two
      traditionally recognized genera: Maianthemum sensu stricto and Smilacina. Thirty
      seven samples representing 22 species of Maianthemum and six closely related
      outgroup taxa were sequenced for eight chloroplast and nuclear markers (trnL-F,
      rps16, rpl16, psbA-trnH, rbcL, ndhF, trnK, and ITS) with a total length of nearly
      10,000 base pairs. Phylogenetic analyses supported the monophyly of Maianthemum
      with Maianthemum sensu stricto nested within Smilacina. Almost all species from
      the eastern Himalayan region in SW China except for Maianthemum tatsienense and
      M. stenolobum form a well supported clade. This clade is characterized
      morphologically by short filaments and large anthers, relatively large flowers,
      and pubescent stems and leaves. Maianthemum tatsienense and M. stenolobum from SW
      to central China form another clade. The other species from eastern Asia (central
      to NE China and Japan) and the New World fall into several clades. The
      intercontinental disjunction between eastern Asia and North America in
      Maianthemum sensu stricto is estimated to be at 1.68 million years ago (mya) with
      the Bayesian relaxed clock relying on uncorrelated rates. A recent radiation at
      about 2.04mya is suggested in the high mountains of SW China, corresponding to
      the geographical heterogeneity in that region after the uplift of the Himalayas.
      Long distance dispersal by birds may have facilitated the evolution of their
      intercontinental disjunction and their biogeographic diversifications in SW
      China.

PMID- 18722540
TI  - Phylogeny of Nolana (Solanaceae) of the Atacama and Peruvian deserts inferred
      from sequences of four plastid markers and the nuclear LEAFY second intron.
AB  - The phylogeny of Nolana (Solanaceae), a genus primarily distributed in the
      coastal Atacama and Peruvian deserts with a few species in the Andes and one
      species endemic to the Galapagos Islands, was reconstructed using sequences of
      four plastid regions (ndhF, psbA-trnH, rps16-trnK and trnC-psbM) and the nuclear
      LEAFY second intron. The monophyly of Nolana was strongly supported by all
      molecular data. The LEAFY data suggested that the Chilean species, including
      Nolana sessiliflora, the N. acuminata group and at least some members of the
      Alona group, are basally diverged, supporting the Chilean origin of the genus.
      Three well-supported clades in the LEAFY tree were corroborated by the SINE
      (short interspersed elements) or SINE-like insertions. Taxa from Peru are grouped
      roughly into two clades. Nolana galapagensis from the Galapagos Island is most
      likely to have derived from a Peruvian ancestor. The monophyly of the
      morphologically well-diagnosed Nolana acuminata group (N. acuminata, N. baccata,
      N. paradoxa, N. parviflora, N. pterocarpa, N. rupicola and N. elegans) was
      supported by both plastid and LEAFY data. Incongruence between the plastid and
      the LEAFY data was detected concerning primarily the positions of N.
      sessiliflora, N. galapagensis, taxa of the Alona group and the two Peruvian
      clades. Such incongruence may be due to reticulate evolution or in some cases
      lineage sorting of plastid DNA. Incongruence between our previous GBSSI trees and
      the plastid-LEAFY trees was also detected concerning two well-supported major
      clades in the GBSSI tree. Duplication of the GBSSI gene may have contributed to
      this incongruence.

PMID- 18722538
TI  - fMRI of supraspinal areas after morphine and one week pancreatic inflammation in
      rats.
AB  - Abdominal pain is a major reason patients seek medical attention yet relatively
      little is known about neuronal pathways relaying visceral pain. We have
      previously characterized pathways transmitting information to the brain about
      visceral pain. Visceral pain arises from second order neurons in lamina X
      surrounding the spinal cord central canal. Some of the brain regions of interest
      receiving axonal terminations directly from lamina X were examined in the present
      study using enhanced functional magnetic resonance imaging (fMRI) before and one
      week after induction of a rat pancreatitis model with persistent inflammation and
      behavioral signs of increased nociception. Analysis of imaging data demonstrates
      an increase in MRI signal for all the regions of interest selected including the
      rostral ventromedial medulla, dorsal raphe, periaqueductal grey, medial thalamus,
      and central amygdala as predicted by the anatomical data, as well as increases in
      the lateral thalamus, cingulate/retrosplenial and parietal cortex. Occipital
      cortex was not activated above threshold in any condition and served as a
      negative control. Morphine attenuated the MRI signal, and the morphine effect was
      antagonized by naloxone in lower brainstem sites. These data confirm activation
      of these specific regions of interest known as integration sites for nociceptive
      information important in behavioral, affective, emotional and autonomic responses
      to ongoing noxious visceral activation.

PMID- 18722541
TI  - Editorial. JAK/STAT signaling in development and disease.

PMID- 18722542
TI  - A model for integration of DNA into the genome during transformation of Fusarium
      graminearum.
AB  - Transformants of Fusarium graminearum were derived using linearized DNA of
      plasmids designed to replace the trichodiene synthase gene, a cutinase gene or a
      xylanase gene with a hygromycin-resistance marker cassette by homologous
      recombination between 1-kbp segments of flanking DNA. Most transformants did not
      exhibit the DNA structure expected of integration by classical double
      recombination. Instead, they contained linearized plasmid joined end-to-end and
      variably incorporated into the genome. Transformant types included ectopic
      integrations and integrations at the target site with or without removal of the
      targeted gene. We have analyzed a large number of transformants using cloning,
      PCR and DNA sequencing to determine the structures of their integrated DNA, and
      describe a model to explain their derivations. The data indicate that 1-3 copies
      of input DNA are first joined end-to-end to produce either linear or circular
      structures, probably mediated by the non-homologous end-joining (NHEJ) system.
      The end-joins typically have 1-5 nucleotides in common and are near or within the
      original cleavage site of the plasmid. Ectopic integrations occur by attaching
      linear DNA to two ends of genomic DNA via the same joining mechanism. Integration
      at the target site is consistent with replication around circularized input DNA,
      beginning and ending within the flanking homologous DNA, resulting in the
      integration of multiple copies of the entire structure. This results in deletion
      or duplication of the target site, or leaves one copy at either end of the
      integrated multimer. Reiterated DNA in the more complex structures is unstable
      due to homologous recombination, such that conversion to simpler forms is
      detected.

PMID- 18722543
TI  - Characteristics of glucose uptake by glucose- and NH4-limited grown Penicillium
      ochrochloron at low, medium and high glucose concentration.
AB  - Glucose uptake by Penicillium ochrochloron (formerly Penicillium simplicissimum)
      was studied from 0.01 to 400 mM glucose using chemostat culture and bioreactor
      batch culture. The characteristics of glucose uptake varied considerably with the
      conditions of growth, harvest and uptake assay. Glucose-limited grown mycelium
      showed one saturable transport system [K(S) below 0.01 mM; v(max) 1.1-1.2 mmol (g
      dry weight)(-1)h(-1)] plus a first order process (permeability P=1.2x10(-7)cm s(
      1)). Ammonium-limited grown mycelium showed only one saturable transport system
      [K(S) 0.3-0.7 mM; v(max) 0.5-0.8 mmol (g dry weight)(-1)h(-1)]. During
      exponential growth at high glucose concentration (300-400 mM) a first order
      process was found with a P value of 5.6-9.3x10(-7)cm s(-1). After ammonium
      exhaustion a second first order phase showed a lower P value (6.1-9.3x10(-8)cm s(
      1)). A similar change in permeability was also found after a re-evaluation of
      published data for Gibberella fujikuroi, Aspergillus niger, Aspergillus awamori
      and Saccharomycopsis lipolytica. For the first order processes simple diffusion
      was ruled out as a mechanism for glucose uptake. Glucose uptake by P.
      ochrochloron was controlled more strongly by metabolism than by transport and was
      not rate limiting for overflow metabolism.

PMID- 18722544
TI  - The role of nitric oxide in reducing deformability of Lewis lung tumor cell
      stimulated by inflammatory cytokines.
AB  - Highly metastatic cells, especially in the lungs, are known to be resistant to
      nitric oxide (NO)-mediated cytotoxicity, compared with poorly or non-metastatic
      cells. However, the precise mechanisms connecting NO and metastasis remain to be
      determined. To clarify the role of NO in the characteristic changes in NO
      resistant cells in response to inflammatory cytokines, we used Lewis lung tumor
      (LLT) cells, which are known to be highly metastatic NO-resistant cells, and
      determined the changes in cell deformability and the gene expression profile
      after the cells were stimulated using cytokine mixture or an NO donor. Both
      exogenous NO and endogenous NO via inducible NO synthase produced by cytokines
      decreased cell deformability by enhancing actin polymerization. The expression of
      several genes associated with actin polymerization was changed so as to increase
      actin filaments in the cells by enhancing actin polymerization and by suppressing
      actin depolymerization, actin filament severing, and barbed-end actin filament
      capping. In conclusion, inflammatory cytokine stimulation reduces deformability
      of LLT cells and enhances actin polymerization which is mainly controlled by the
      same genes induced by NO.

PMID- 18722545
TI  - Cold stress and light signals induce the expression of cold-inducible RNA binding
      protein (cirp) in the brain and eye of the Japanese treefrog (Hyla japonica).
AB  - Hibernation is an important physiological animal behavior. However, the molecular
      mechanism by which hibernation is regulated remains unknown. The Japanese
      treefrog (Hyla japonica) usually hibernates in the winter. Since this treefrog is
      an ectothermic animal, its hibernation is thought to be linked to the
      environmental temperature. In murine cells, gene expression for the cold
      inducible RNA binding protein (cirp) is induced simply by cold stress. Therefore,
      it was hypothesized that the treefrog would also have increased expression of
      cirp during the hibernation season. In this report, we describe the cloning of
      the treefrog cirp gene and a quantitative analysis of its expression with real
      time PCR. Like its homologs, treefrog cirp was found to be expressed in response
      to a cold stress, and its transcript was detectable in the brain, eye and ovary.
      Furthermore, we found that light signals could also induce the expression of
      cirp, and the total amount of cirp expression in both the brain and eye was
      significantly higher in December than in July. These results suggest that the
      expression of cirp in this treefrog is physiologically induced by environmental
      factors, such as cold stress or light signals.

PMID- 18722546
TI  - Cloning and characterization of a cDNA clone encoding troponin T from tick
      Haemaphysalis qinghaiensis (Acari: Ixodidae).
AB  - Troponin T (TnT) is a key protein for Ca(2+)-sensitive molecular switching of
      muscle contraction. The entire cDNA sequence of Haemaphysalis qinghaiensis
      troponin T gene (HqTnT) from the hard tick was cloned here. The cDNA sequence of
      HqTnT possesses an ORF of 1170 bp coding for a mature protein with 389 amino acid
      residues and a molecular mass of 46.5 kDa. Search of the cloned sequence in
      GenBank revealed that HqTnT gene shared some homology with TnT genes of other
      organisms. By sequence comparison, two conserved domains were identified in the
      middle (residues 54-78) and close to the carboxyl-terminal end (residues 181-229)
      of the amino acid sequence of HqTnT. These conserved domains might be responsible
      for the interaction with tick tropomyosin and troponin I subunit, respectively.
      Reverse transcription-polymerase chain reaction showed a ubiquitous expression of
      HqTnT gene at different developmental stages and in different tissues of the
      tick. The HqTnT was expressed as glutathione S-transferase fused protein in a
      prokaryotic system. Though rHqTnT could induce specific antibodies in sheep, the
      antibodies could not protect sheep from the infestation of ticks. Therefore,
      recombinantly produced HqTnT could not be a candidate antigen for developing anti
      tick vaccine. To our knowledge, this is the first report of tick TnT gene.

PMID- 18722548
TI  - Expression of Ca(2+)-independent and Ca(2+)-dependent phospholipases A(2) and
      cyclooxygenases in human melanocytes and malignant melanoma cell lines.
AB  - We provide novel evidence that human melanoma cell lines (M10, M14, SK-MEL28, SK
      MEL93, 243MEL, 1074MEL, OCM-1, and COLO38) expressed, at mRNA and protein levels,
      either Ca(2+)-independent phospholipase A(2) (iPLA(2)) or cytosolic phospholipase
      A(2) (cPLA(2)) and its phosphorylated form. Normal human melanocytes contained
      the lowest levels of both PLA(2)s. Cyclooxygenase-1 and -2 (COX-1 and COX-2) were
      also expressed in cultured tumor cells as measured by Western blots. The most
      pronounced overexpression of iPLA(2) and COX-1 was found in two melanoma-derived
      cells, M14 and COLO38. Normal human melanocytes and the M10 melanoma cell line
      displayed no COX-2 expression. Using subcellular fractionation, Western blot and
      confocal microcopy analyses, in paradigmatic SK-MEL28 and SK-MEL93 cells we
      showed that iPLA(2), COX-1 and even cPLA(2) were equally located in the cytosol,
      membrane structures and perinuclear region while COX-2 was preferentially
      associated with the cytosol. Specific inhibitors of these three enzymes
      significantly reduced the basal proliferation rate either in melanocytes or in
      melanoma cell lines. These results, coupled with the inhibition of the cell
      proliferation by electroporation of melanoma cells with cPLA(2) or COX-2
      antibodies, demonstrate that a possible correlation between PLA(2)-COX expression
      and tumor cell proliferation in the melanocytic system does exist. In addition,
      the high expression level of both PLA(2)s and COXs suggests that eicosanoids
      modulate cell proliferation and tumor invasiveness.

PMID- 18722547
TI  - The trefoil factor interacting protein TFIZ1 binds the trefoil protein TFF1
      preferentially in normal gastric mucosal cells but the co-expression of these
      proteins is deregulated in gastric cancer.
AB  - The gastric tumour suppressor trefoil protein TFF1 is present as a covalently
      bound heterodimer with a previously uncharacterised protein, TFIZ1, in normal
      human gastric mucosa. The purpose of this research was firstly to examine the
      molecular forms of TFIZ1 present, secondly to determine if TFIZ1 binds other
      proteins apart form TFF1 in vivo, thirdly to investigate if TFIZ1 and TFF1 are co
      regulated in normal gastric mucosa and fourthly to determine if their co
      regulation is maintained or disrupted in gastric cancer. We demonstrate that
      almost all human TFIZ1 is present as a heterodimer with TFF1 and that TFIZ1 is
      not bound to either of the other two trefoil proteins, TFF2 and TFF3. TFIZ1 and
      TFF1 are co-expressed by the surface mucus secretory cells throughout the stomach
      and the molecular forms of each protein are affected by the relative abundance of
      the other. TFIZ1 expression is lost consistently, early and permanently in
      gastric tumour cells. In contrast, TFF1 is sometimes expressed in the absence of
      TFIZ1 in gastric cancer cells and this expression is associated with metastasis
      (lymph node involvement: p=0.007). In conclusion, formation of the heterodimer
      between TFIZ1 and TFF1 is a specific interaction that occurs uniquely in the
      mucus secretory cells of the stomach, co-expression of the two proteins is
      disrupted in gastric cancer and expression of TFF1 in the absence of TFIZ1 is
      associated with a more invasive and metastatic phenotype. This indicates that
      TFF1 expression in the absence of TFIZ1 expression has potentially deleterious
      consequences in gastric cancer.

PMID- 18722550
TI  - T2 relaxation time correlates of face recognition deficits in temporal lobe
      epilepsy.
AB  - This study explored structural correlates of immediate and delayed face
      recognition in 22 nonsurgical patients with nonlesional, unilateral mesial
      temporal lobe epilepsy (TLE, 10 left/12 right). We measured T2 relaxation time
      bilaterally in the hippocampus, the amygdala, and the fusiform gyrus. Apart from
      raised T2 values in the ipsilateral hippocampus, we found increased T2 values in
      the ipsilateral amygdala. Patients with right TLE exhibited impaired face
      recognition as a result of a decrease from immediate to delayed recognition.
      Higher T2 values in the right than left fusiform gyrus or hippocampus were
      related to worse immediate face recognition, but did not correlate with 24-hour
      face recognition. These preliminary results indicate that structural changes in
      the fusiform gyrus and hippocampus may influence immediate face recognition
      deficits, but have no linear influence on long-term face recognition in TLE. We
      suggest that long-term face recognition depends on a right hemispheric network
      encompassing structures outside the temporal lobe.

PMID- 18722549
TI  - Cold acclimation induces physiological cardiac hypertrophy and increases
      assimilation of triacylglycerol metabolism through lipoprotein lipase.
AB  - The contribution of triacylglycerol to energy provision in the hypertrophied
      heart, mediated through lipoprotein lipase (LPL) is largely unknown and the
      contribution of very-low-density lipoprotein (VLDL) receptor to control of LPL
      presentation at the endothelium is unclear. For isolated perfused rat hearts,
      cold acclimation (CA) induced volume-overload hypertrophy, with decreased
      developed pressure (P<0.01), increased end-diastolic volume of the left ventricle
      (P<0.001) and a loss of contractile reserve in response to dobutamine challenge
      (P<0.01). Oleate utilisation by perfused hearts was unchanged by CA, however
      uptake of intralipid emulsion increased 3-fold (P<0.01). CA increased the
      proportion of lipid deposited in tissue lipids from 10% in euthermic controls to
      40% (P<0.01) although the overall contribution of individual lipid classes was
      unaffected. Cold acclimation significantly increased heparin-releasable LPL
      (P<0.05) and tissue residual LPL (P<0.01). Western blot analysis indicated
      preserved expression of proteins coding for SERCA2, muscle-CPT1 and VLDL-receptor
      following CA, while AMPKalpha2 and phospho-AMPKalpha2 were unaffected. These
      observations indicate that for physiological hypertrophy AMPK phosphorylation
      does not mediate the enhanced translocation of LPL to cardiac endothelium.

PMID- 18722551
TI  - Toward a molecular equivalent dose: use of the medaka model in comparative risk
      assessment.
AB  - Recent changes in the risk assessment landscape underscore the need to be able to
      compare the results of toxicity and dose-response testing between a growing list
      of animal models and, quite possibly, an array of in vitro screening assays. How
      do we compare test results for a given compound between vastly different species?
      For example, what dose level in the ambient water of a small fish model would be
      equivalent to 10 ppm of a given compound in the rat's drinking water? Where do we
      begin? To initially address these questions, and in order to compare dose
      response tests in a standard rodent model with a fish model, we used the concept
      of molecular dose. Assays that quantify types of DNA damage that are directly
      relevant to carcinogenesis integrate the factors such as chemical exposure,
      uptake, distribution, metabolism, etc. that tend to vary so widely between
      different phyletic levels. We performed parallel exposures in F344 rats and
      Japanese medaka (Oryzias latipes) to the alkylating hepatocarcinogen,
      dimethylnitrosamine (DMN). In both models, we measured the DNA adducts 8
      hydroxyguanine, N(7)-methylguanine and O(6)-methylguanine in the liver; mutation
      frequency using lambda cII transgenic medaka and lambda cII transgenic (Big
      Blue(R)) rats; and early morphological changes in the livers of both models using
      histopathology and immunohistochemistry. Pulse dose levels in fish were 0, 10,
      25, 50, or 100 ppm DMN in the ambient water for 14 days. Since rats are reported
      to be especially sensitive to DMN, they received 0, 0.1, 1, 5, 10, or 25 ppm DMN
      in the drinking water for the same time period. While liver DNA adduct
      concentrations were similar in magnitude, mutant frequencies in the DMN-exposed
      medaka were up to 20 times higher than in the Big Blue rats. Future work with
      other compounds will generate a more complete picture of comparative dose
      response between different phyletic levels and will help guide risk assessors
      using "alternative" models.

PMID- 18722552
TI  - Heat shock protein (Hsp) gene responses of the intertidal copepod Tigriopus
      japonicus to environmental toxicants.
AB  - The induction of heat shock proteins (Hsps) is considered as an important
      protective, ecophysiologically adaptive, and genetically conserved response to
      environmental stress in all organisms. Among the Hsps, the heat shock protein 70
      (Hsp70) family members are most extensively studied for their characterization
      and induction in response to environmental stressors in a range of species. We
      studied expression of ten Hsp transcripts in response to heat treatment in an
      intertidal marine copepod Tigriopus japonicus and observed that expression of
      Hsp70 was more pronounced than other Hsps. Subsequently, cDNA and genomic
      sequences of T. japonicus Hsp70 (TJ-Hsp70) were worked out by molecular cloning
      techniques and phylogenetic relationship was analyzed. The bacterial expression
      of TJ-Hsp70 and its expression in response to metal and endocrine-disrupting
      chemical (EDC) exposures were also studied. The TJ-Hsp70 transformed bacteria
      showed increased thermotolerance compared to bacteria with vector only. All the
      trace metals (i.e. copper, silver, and zinc) caused a concentration-dependent
      increase in the expression of Hsp70 transcripts. Effect of EDCs on Hsp70
      expression was differential. While 4-nonylphenol (NP) and 4-t-octylpheno (OP)
      caused downregulation, bisphenol A (BPA) caused upregulation. The promoter region
      of the genomic Hsp70 sequence contained putative xenobiotic response elements
      (XREs) indicating that TJ-Hsp70 regulation not only by temperature but also by
      xenobiotics. These findings suggest that in T. japonicus, Hsp70 has a conserved
      role of thermotolerance and its expression in response to xenobiotics exposure
      appears to be a protective response.

PMID- 18722553
TI  - Endothelial pathomechanisms in acute lung injury.
AB  - Acute lung injury (ALI) and its most severe extreme the acute respiratory
      distress syndrome (ARDS) refer to increased-permeability pulmonary edema caused
      by a variety of pulmonary or systemic insults. ALI and in particular ARDS, are
      usually accompanied by refractory hypoxemia and the need for mechanical
      ventilation. In most cases, an exaggerated inflammatory and pro-thrombotic
      reaction to an initial stimulus, such as systemic infection, elicits disruption
      of the alveolo-capillary membrane and vascular fluid leak. The pulmonary
      endothelium is a major metabolic organ promoting adequate pulmonary and systemic
      vascular homeostasis, and a main target of circulating cells and humoral
      mediators under injury; pulmonary endothelium is therefore critically involved in
      the pathogenesis of ALI. In this review we will discuss mechanisms of pulmonary
      endothelial dysfunction and edema generation in the lung with special emphasis on
      the interplay between the endothelium, the immune and hemostatic systems, and
      highlight how these principles apply in the context of defined disorders and
      specific insults implicated in ALI pathogenesis.

PMID- 18722554
TI  - Mitochondrial genome analysis of Ochotona curzoniae and implication of cytochrome
      c oxidase in hypoxic adaptation.
AB  - Pikas originated in Asia and are small lagomorphs native to cold climates. The
      plateau pika, Ochotona curzoniae is a keystone species on the Qinghai-Tibet
      Plateau and an ideal animal model for hypoxic adaptation studies. Altered
      mitochondrial function, especially cytochrome c oxidase activity, is an important
      factor in modulation of energy generation and expenditure during cold and hypoxia
      adaptation. In this study, we determined the complete nucleotide sequence of the
      O. curzoniae mitochondrial genome. The plateau pika mitochondrial DNA is 17,131bp
      long and encodes the complete set of 37 proteins typical for vertebrates.
      Phylogenetic analysis based on concatenated heavy-strand encoded protein-coding
      genes revealed that pikas are closer to rabbit and hare than to rat. This
      suggests that rabbit or hare would be a good control animal for pikas in cold and
      hypoxia adaptation studies. Fifteen novel mitochondrial DNA-encoded amino acid
      changes were identified in the pikas, including three in the subunits of
      cytochrome c oxidase. These amino acid substitutions potentially function in
      modulation of mitochondrial complexes and electron transport efficiency during
      cold and hypoxia adaptation.

PMID- 18722556
TI  - Regulation of double-stranded DNA gap repair by the RAD6 pathway.
AB  - The RAD6 pathway allows replication across DNA lesions by either an error-prone
      or error-free mode. Error-prone replication involves translesion polymerases and
      requires monoubiquitylation at lysine (K) 164 of PCNA by the Rad6 and Rad18
      enzymes. By contrast, the error-free bypass is triggered by modification of PCNA
      by K63-linked polyubiquitin chains, a reaction that requires in addition to Rad6
      and Rad18 the enzymes Rad5 and Ubc13-Mms2. Here, we show that the RAD6 pathway is
      also critical for controlling repair pathways that act on DNA double-strand
      breaks. By using gapped plasmids as substrates, we found that repair in wild-type
      cells proceeds almost exclusively by homology-dependent repair (HDR) using
      chromosomal DNA as a template, whereas non-homologous end-joining (NHEJ) is
      suppressed. In contrast, in cells deficient in PCNA polyubiquitylation, plasmid
      repair occurs largely by NHEJ. Mutant cells that are completely deficient in PCNA
      ubiquitylation, repair plasmids by HDR similar to wild-type cells. These findings
      are consistent with a model in which unmodified PCNA supports HDR, whereas PCNA
      monoubiquitylation diverts repair to NHEJ, which is suppressed by PCNA
      polyubiquitylation. More generally, our data suggest that the balance between HDR
      and NHEJ pathways is crucially controlled by genes of the RAD6 pathway through
      modifications of PCNA.

PMID- 18722555
TI  - Roles of the Werner syndrome RecQ helicase in DNA replication.
AB  - Congenital deficiency in the WRN protein, a member of the human RecQ helicase
      family, gives rise to Werner syndrome, a genetic instability and cancer
      predisposition disorder with features of premature aging. Cellular roles of WRN
      are not fully elucidated. WRN has been implicated in telomere maintenance,
      homologous recombination, DNA repair, and other processes. Here I review the
      available data that directly address the role of WRN in preserving DNA integrity
      during replication and propose that WRN can function in coordinating replication
      fork progression with replication stress-induced fork remodeling. I further
      discuss this role of WRN within the contexts of damage tolerance group of
      regulatory pathways, and redundancy and cooperation with other RecQ helicases.

PMID- 18722557
TI  - Metabolic control of T cell activation and death in SLE.
AB  - Systemic lupus erythematosus (SLE) is characterized by abnormal T cell activation
      and death, processes which are crucially dependent on the controlled production
      of reactive oxygen intermediates (ROI) and of ATP in mitochondria. The
      mitochondrial transmembrane potential (Deltapsi(m)) has conclusively emerged as a
      critical checkpoint of ATP synthesis and cell death. Lupus T cells exhibit
      persistent elevation of Deltapsi(m) or mitochondrial hyperpolarization (MHP) as
      well as depletion of ATP and glutathione which decrease activation-induced
      apoptosis and instead predispose T cells for necrosis, thus stimulating
      inflammation in SLE. NO-induced mitochondrial biogenesis in normal T cells
      accelerates the rapid phase and reduces the plateau of Ca(2+) influx upon
      CD3/CD28 co-stimulation, thus mimicking the Ca(2+) signaling profile of lupus T
      cells. Treatment of SLE patients with rapamycin improves disease activity,
      normalizes CD3/CD28-induced Ca(2+) fluxing but fails to affect MHP, suggesting
      that altered Ca(2+) fluxing is downstream or independent of mitochondrial
      dysfunction. Understanding the molecular basis and consequences of MHP is
      essential for controlling T cell activation and death signaling in SLE.

PMID- 18722559
TI  - Altered B-cell signaling in lupus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease of complex etiology
      primarily characterized by the presence of high titers of autoantibodies
      targeting many nuclear as well as cytoplasmic antigens, with resultant end-organ
      damage. Aberrant signaling events have been documented in various lymphocyte
      populations, and they have constituted attractive targets for therapeutic
      intervention. Murine models of lupus (conventional or engineered) have yielded
      interesting snapshots of the signaling status of lupus lymphocytes, and many of
      these alterations in cell signaling observed in murine models of lupus have also
      been documented in patient samples. Analyses of B-cell signaling in various
      murine lupus models have not only provided an in-depth perspective of the
      signaling status and possibly the underlying mechanisms leading to enhanced
      survival of autoimmune B cells, but have also presented us with potential
      strategies for treating lupus.

PMID- 18722558
TI  - Toll-like receptors in systemic lupus erythematosus; prospects for therapeutic
      intervention.
AB  - Recent experimental and clinical studies have placed new emphasis on the role of
      the innate immune system in SLE. Nucleic acid-containing immune complexes
      activate the innate response by engaging specific Toll-like receptors (TLRs) and
      promote the generation of autoantibodies. Pharmacologic modulation of TLR
      directed pathways may offer new therapeutic approaches for the treatment of SLE.

PMID- 18722560
TI  - Overview of signal processing by the immune system in systemic lupus
      erythematosus.

PMID- 18722561
TI  - Osteoimmunology--the hidden immune regulation of bone.
AB  - Osteoimmunology is an emerging field of research dedicated to the investigation
      of the interactions between the immune and skeletal systems. These interactions
      are not only mediated by the release of cytokines and chemokines but also by
      direct cell-cell contact. Recently, it was proposed that immunoreceptors found in
      the immune cells are also an essential signal for osteoclasts activation, along
      with receptor activator NF-kappaB (RANK) ligand (RANKL) and macrophage-colony
      stimulating factor (M-CSF). In addition, adipose tissue also produces several
      factors (adipokines) that are known to interfere with the immune system and bone
      homeostasis. Chronic inflammation strongly influences osteoimmunology determining
      profound metabolic, structural and functional changes in bone.

PMID- 18722565
TI  - Identifying high-risk regions for schistosomiasis in Guichi, China: a spatial
      analysis.
AB  - Schistosomiasis epidemic is reemerging in some areas of China. The extensive
      snail habitat is a major challenge for a sustainable schistosomiasis control.
      Direct surveillance on snails for the disease control is no longer a desirable
      disease control approach due to current low density of infected snails and
      reduced funding. In this study the benefit of indirect monitoring of acute
      schistosomiasis cases, using spatial methods including disease mapping and
      spatial clustering analysis was explored in Guichi, China. Significant global
      clustering existed for acute cases and two statistically significant spatial
      clusters were detected, and subsequently validated by field surveys. Our study
      indicates that the application of geographic information system (GIS) and spatial
      methods are useful in the epidemiologic surveillance and risk assessment for
      acute schistosomiasis, providing an alternative approach with minimal funds
      required.

PMID- 18722563
TI  - Identification of neurotransmitters and co-localization of transmitters in
      brainstem respiratory neurons.
AB  - Identifying the major ionotropic neurotransmitter in a respiratory neuron is of
      critical importance in determining how the neuron fits into the respiratory
      system, whether in producing or modifying respiratory drive and rhythm. There are
      now several groups of respiratory neurons whose major neurotransmitters have been
      identified and in some of these cases, more than one transmitter has been
      identified in particular neurons. This review will describe the physiologically
      identified neurons in major respiratory areas that have been phenotyped for major
      ionotropic transmitters as well as those where more than one transmitter has been
      identified. Although the purpose of the additional transmitter has not been
      elucidated for any of the respiratory neurons, some examples from other systems
      will be discussed.

PMID- 18722564
TI  - Histone modifying enzymes: structures, mechanisms, and specificities.
AB  - Histone modifying enzymes catalyze the addition or removal of an array of
      covalent modifications in histone and non-histone proteins. Within the context of
      chromatin, these modifications regulate gene expression as well as other genomic
      functions and have been implicated in establishing and maintaining a heritable
      epigenetic code that contributes to defining cell identity and fate. Biochemical
      and structural characterization of histone modifying enzymes has yielded
      important insights into their respective catalytic mechanisms, substrate
      specificities, and regulation. In this review, we summarize recent advances in
      understanding these enzymes, highlighting studies of the histone
      acetyltransferases (HATs) p300 (also now known as KAT3B) and Rtt109 (KAT11) and
      the histone lysine demethylases (HDMs) LSD1 (KDM1) and JMJD2A (KDM4A), present
      overriding themes that derive from these studies, and pose remaining questions
      concerning their regulatory roles in mediating DNA transactions.

PMID- 18722567
TI  - T2-weighted cardiovascular magnetic resonance to identify infarct-associated
      edema in early pregnancy.

PMID- 18722568
TI  - Endothelial progenitor cells and pregnancy.

PMID- 18722569
TI  - Analysis of urologic complications after radical hysterectomy.
AB  - OBJECTIVE: Injuries of the ureter or bladder or development of vesicovaginal and
      ureterovaginal fistulas are the most serious complications in gynecological
      surgery. STUDY DESIGN: This study included 536 women who underwent radical
      hysterectomy because of invasive cancer of the cervix uteri. RESULTS: During the
      surgery the ureter was injured in 1.32% of cases, whereas the percentage of
      bladder injuries was 1.49. In the early postoperative period vesicovaginal or
      ureterovaginal fistulas appeared in 2.61% and 2.43% of cases, respectively.
      CONCLUSION: The stage of the disease, obesity, diabetes, and postoperative
      surgical infection acted as predisposing factors of the urinary tract
      complications.

PMID- 18722570
TI  - Perinatal outcomes among different Asian-American subgroups.
AB  - OBJECTIVE: The objective of the study was to investigate the differences in
      perinatal outcomes between various Asian ethnic subgroups at a national level.
      STUDY DESIGN: This is a retrospective cohort study of all non-Hispanic Chinese,
      Japanese, Filipino, Asian Indian, Korean, Vietnamese, Samoan, Guamanian, and
      Hawaiian women whose deliveries were recorded by US birth certificates within the
      year 2003. Perinatal outcomes were compared between groups and potential
      confounders controlled for with multivariable logistic regression. RESULTS: We
      found significant differences (P < .001) in the incidence of all perinatal
      outcomes of interest among the different Asian subgroups. These differences
      persisted after adjusting for potential confounders. The incidence of diabetes in
      pregnancy varied from 2.9% (Korean) to 5.7% (Filipina). CONCLUSION: Our study
      demonstrates significant differences in preterm labor, primary cesarean delivery,
      pregnancy-associated hypertension, eclampsia, diabetes in pregnancy, low
      birthweight, macrosomia, and cephalopelvic disproportion among Asian subgroups at
      a national level, affirming the importance of examining these subgroups
      separately.

PMID- 18722571
TI  - Attrition in residents entering US obstetrics and gynecology residencies:
      analysis of National GME Census data.
AB  - OBJECTIVE: We sought to identify risk factors for attrition among obstetrics and
      gynecology residents. STUDY DESIGN: We analyzed 2001-2006 American Medical
      Association Graduate Medical Education (GME) Census data for all residents who
      entered obstetrics and gynecology in 2001 to characterize residents who did not
      complete a 4-year training period in their initial programs ("attrition").
      Multivariable logistic regression models identified predictors of attrition from
      among age, gender, race, Hispanic ethnicity, medical school type, and medical
      school graduation year. RESULTS: Of 1055 residents entering obstetrics and
      gynecology in 2001, 228 (21.6%) were in the "attrition" group (133 changed
      obstetrics and gynecology programs and/or completed training on atypical cycles;
      75 changed specialty; 20 discontinued GME). Residents who were older,
      underrepresented minority race, Asian race, osteopathic- or international medical
      school graduates were more likely to be in the "attrition" group (each P < .05).
      CONCLUSION: Analysis of a national cohort of obstetrics and gynecology residents
      identified substantial attrition and demographic risk factors.

PMID- 18722572
TI  - Peripartum cardiomyopathy: prognostic factors for long-term maternal outcome.
AB  - OBJECTIVE: The objective of the study was to assess the prognostic value of
      ejection fraction (EF) at index and subsequent pregnancy on long-term outcome in
      patients with peripartum cardiomyopathy (PPCM). STUDY DESIGN: Seventy PPCM
      patients met inclusion criteria. Patients had echocardiography evaluations at the
      index pregnancy, at interval follow-up (F/U) or at the beginning of a subsequent
      pregnancy and the last F/U study available. Outcome data were echocardiographic
      parameters and the subsequent need for cardiac transplant. RESULTS: Patients were
      categorized on the basis of their initial EF into EF of 25% or less and EF
      greater than 25% and stratified on the basis of their pregnancy into the
      following groups: group 1 (n = 33), no subsequent pregnancy; group 2 (n = 16),
      subsequent pregnancy with early termination; and group 3 (n = 21), successful
      subsequent pregnancy. F/U from index pregnancy to final F/U was 3.4+/-1.9 (range,
      1-6 years). Groups 1 and 2 had persistent left ventricular dysfunction at all
      echocardiographic evaluations. In group 3, despite a mean EF greater than 40% at
      a subsequent pregnancy, 29% had worsening cardiac symptoms. Among 28 patients
      with EF of 25% or less, 16 (57%) had end-stage cardiac disease. One had a
      transplant and 15 were on a transplant list. All 16 had a baseline EF 25% or less
      at index pregnancy: 4 had improved (EF greater than 40%) at interval F/U and 3 at
      last F/U available. CONCLUSION: Women with a history of PPCM had a higher rate of
      progression of symptoms of heart failure in a subsequent pregnancy. A baseline
      left ventricular EF 25% or less at index pregnancy is associated with a higher
      rate of cardiac transplant.

PMID- 18722573
TI  - A randomized trial comparing 2 outpatient educational settings for clerkship
      students: private practice office vs hospital clinic.
AB  - OBJECTIVE: The purpose of this study was to compare medical students' experiences
      in 2 outpatient educational settings. STUDY DESIGN: For their 2-week ambulatory
      rotation, all 76 medical students were randomized to either a hospital clinic or
      a private office. Seventy students completed the survey. RESULTS: When compared
      to students working in a private office setting, hospital clinic students
      reported more breast exams, speculum exams, uterine fundal height measurements,
      wet mount reading, contraceptive counseling, and first obstetrical and
      gynecologic patient visits. Students in the hospital clinic were more likely to
      report having educationally valuable opportunities to interview and examine
      patients and to discuss the differential diagnosis with their preceptor.
      Nevertheless, medical students randomized to the private office were more likely
      to report considering obstetrics and gynecology as a career. CONCLUSION: The
      hospital clinic provided students with more clinical experiences. Medical
      students assigned to a private office, however, were more likely to consider
      obstetrics and gynecology as a career.

PMID- 18722574
TI  - Blood pressure augmentation and maternal circulating concentrations of angiogenic
      factors at delivery in preeclamptic and uncomplicated pregnancies.
AB  - OBJECTIVE: The objective of the study was to determine whether blood pressure
      increases are associated with maternal angiogenic factors in uncomplicated and
      preeclamptic pregnancies. STUDY DESIGN: Associations of blood pressure increases
      from mid- to late pregnancy with maternal serum concentrations of soluble fms
      like tyrosine kinase receptor (sFlt1), soluble endoglin (sEng), and placental
      growth factor (PlGF) at delivery were analyzed in 43 uncomplicated and 44
      preeclamptic pregnancies. RESULTS: In uncomplicated pregnancies, increases in
      diastolic and mean arterial pressure were inversely associated with PlGF at
      delivery and positively associated with sEng and sFlt1/PlGF ratio. There were no
      significant associations between blood pressure increases and angiogenic factor
      concentrations in preeclampsia. CONCLUSION: These data suggest that angiogenic
      factors are involved in blood pressure modulation in normotensive pregnancy and
      are consistent with the hypothesis that angiogenic balance plays a role in
      maternal breast cancer risk reduction associated with mid- to late blood pressure
      increases in uncomplicated pregnancies.

PMID- 18722575
TI  - Challenge with ovalbumin antigen increases uterine and cervical contractile
      activity in sensitized guinea pigs.
AB  - OBJECTIVE: The aims of this study were to investigate the effects of ovalbumin
      challenge on uterine and cervical contractility, intrauterine pressure, and
      uterine electromyography activity in sensitized guinea pigs. STUDY DESIGN: Guinea
      pigs were sensitized by injection of ovalbumin-aluminum hydroxide suspension.
      Control animals were injected with the aluminum hydroxide suspension only. On
      days 55-57 of pregnancy, longitudinal uterine and cervical strips from guinea
      pigs were prepared for isometric tension recording. Nonpregnant guinea pigs were
      outfitted with telemetric transducers to record intrauterine pressure and uterine
      electromyography. RESULTS: Ovalbumin significantly increased contractility of
      uterine and cervical strips from sensitized versus nonsensitized animals. These
      effects were abolished by histamine H(1) receptor antagonist in uterine strips
      and by histamine H(1) receptor antagonist and a mast cell stabilizer in cervical
      strips from sensitized animals. Cyclooxygenase and 5-lipoxygenase inhibitors had
      no significant effect on the response to ovalbumin. Treatment with ovalbumin in
      vivo significantly increased intrauterine pressure and uterine electromyography
      activity in sensitized but not in nonsensitized, animals. CONCLUSION: Our
      findings indicate that type I hypersensitivity reactions may be important in
      mediating uterine contractility in pregnant and nonpregnant states.

PMID- 18722576
TI  - Acute effects of selective fetoscopic laser photocoagulation on recipient cardiac
      function in twin-twin transfusion syndrome.
AB  - OBJECTIVE: This study evaluated the acute effects of selective fetoscopic laser
      photocoagulation (SFLP) on recipient cardiovascular function in a twin-twin
      transfusion syndrome (TTTS) pregnancy. STUDY DESIGN: This was a retrospective
      chart review of echocardiographic data in TTTS including right (RV) and left (LV)
      ventricular Doppler myocardial performance index (MPI); LV and RV end diastolic
      wall thickness; and umbilical artery (UA), vein (UV), and ductus venosus (DV)
      Dopplers. The primary outcome measures were improved MPI defined as greater than
      10% interval decrease in left and/or right MPI. Data were analyzed by Student t
      test and Fisher's exact test. RESULTS: Sixty-five patients met inclusion
      criteria. SFLP results in a significant improvement in UV and DV Doppler and an
      increase in both RV and LV wall thickness. A 10% or greater improvement in
      recipient LV MPI after SFLP is associated with improved recipient survival as
      compared with unimproved LV MPI (100% vs 86.1%, P = .05). CONCLUSION: Improved
      recipient myocardial performance index after SFLP is associated with improvement
      in recipient survival.

PMID- 18722577
TI  - Vaginal hysterectomy for endometrial cancers.

PMID- 18722578
TI  - When will we actually conduct a risk-adjusted surgical audit worldwide?

PMID- 18722579
TI  - Relevant recertification-a problem for specialty boards.

PMID- 18722580
TI  - Impact of intraoperative myocardial tissue acidosis on postoperative adverse
      outcomes and cost of care for patients undergoing prolonged aortic clamping
      during cardiopulmonary bypass.
AB  - BACKGROUND: This study examined the impact of intraoperative myocardial acidosis
      and adverse postoperative outcomes on the cost of cardiac surgical care. METHODS:
      Myocardial tissue pH corrected to 37 degrees C (pH(37C)) was measured in 162
      patients with cross-clamp (XC) duration of 119 minutes or longer. Perioperative
      data and outcomes were collected prospectively. The Veterans Affairs cost
      accounting system was used to determine the cost of care in a subset of 57
      patients. RESULTS: Long XC duration was associated with significantly increased
      acidosis and adverse postoperative outcomes. The cost of care for patients with
      adverse outcomes was increased by 110% (P < .0001). Patients with acidosis at the
      end of reperfusion had significantly (P = .0470) increased costs of care. End
      reperfusion of myocardial tissue pH(37C) of less than 7.0, diabetes mellitus, and
      body surface area were significant determinants of postoperative adverse
      outcomes. CONCLUSIONS: Intraoperative myocardial acidosis is a determinant of
      postoperative adverse outcomes and cost in cardiac surgery. Reducing XC duration
      and improving intraoperative myocardial protection should improve outcomes and
      reduce cost.

PMID- 18722581
TI  - Clinical images. Gastric perforation caused by metastatic lung carcinoma.
AB  - A case of gastric perforation caused by metastases of small-cell lung carcinoma
      in an 85-year-old man is reported. This complication revealed the neoplasm.
      Biopsy should always be done in patients with gastric perforations, even if there
      is no palpable tumor. Minimal surgery is warranted because this event occurs
      often in patients with advanced disease and poor prognosis.

PMID- 18722582
TI  - Complications of endoscopic retrograde cholangiopancreatography: when to operate?
      An algorithmic approach.

PMID- 18722583
TI  - An evidence-based medicine review of lymphadenectomy extent for gastric cancer.
AB  - BACKGROUND: Several studies in the literature have investigated the possible role
      of the extent of lymphadenectomy in gastric cancer treatment failure. The current
      study attempted to determine the effectiveness and safety of lymphadenectomy with
      gastrectomy for the treatment of gastric cancer. METHODS: Randomized controlled
      trials (RCTs) were identified by means of MEDLINE, EMBASE, Cochrane Controlled
      Trials Register databases, and Chinese Biomedical Database, as well as by
      selecting references from relevant articles. RESULTS: Overall, 14 RCTs (3,432
      patients) were included in the meta-analysis. Of the D1 and D2 surgery groups,
      the operative mortality and postoperative morbidity were higher in the D2 group
      than in the D1 group, but the 3- and 5-year survival rates were not statistically
      different. Also the operative time was shorter in D1 compared to D2. In the D2
      versus the D3 surgical group, the operative mortality, percentage of
      postoperative complications, operative time, and hospital stay were not
      significantly different. CONCLUSIONS: The results suggest that D2 and D3 surgery
      may not offer specific advantages for gastric cancer and instead may lead to
      disadvantages for patient outcomes.

PMID- 18722584
TI  - Osteochondroma developing from the xyphoid appendix into an abdominal wall scar
      from a previous laparotomy.
AB  - We describe herein the case of a 45-year-old man who developed an osteochondroma
      from the xyphoid appendix into an abdominal wall scar from a laparotomy performed
      4 years previously. To our knowledge, rare cases of osteochondroma of the xyphoid
      bone have been documented in the literature. As shown by the tumor's rapid
      development during a period of only 4 years, osteochondromas arise from, or grow
      well under, inflammatory and cicatricial conditions. Periosteal contusion causing
      growth-plate cartilage migration and enchondral ossification seems to be the
      first presentation of osteochondroma.

PMID- 18722585
TI  - Spaced education improves the feedback that surgical residents give to medical
      students: a randomized trial.
AB  - BACKGROUND: Surgery residents teach medical students; feedback is one critical
      teaching skill. We investigated whether feedback given by surgery residents to
      students could be improved through an online spaced education program. METHODS:
      Surgery residents were randomized to receive either a weekly spaced education e
      mail during a 9-month period containing teaching bullets on how to provide
      effective feedback, or no intervention. Medical students rated the frequency and
      quality of feedback they received from the residents. RESULTS: Students reported
      45% (67 of 149) of the spaced education residents gave frequent feedback,
      compared with 31% (55 of 175) of control residents (relative risk [RR], 1.43; P =
      .016). Students reported resident feedback was "helpful in their learning" in 92%
      (132 of 143) of their evaluations of spaced education residents, compared with
      82% (132 of 161) of their evaluations of control residents (RR, 1.13; P = .01).
      CONCLUSIONS: Educational programs using feedback bullets e-mailed weekly can
      significantly improve the frequency and quality of feedback that surgical
      residents provide medical students.

PMID- 18722586
TI  - A promising new alternative for the rapid reversal of warfarin coagulopathy in
      traumatic intracranial hemorrhage.
AB  - BACKGROUND: Internationally, Factor IX complex (FIX complex) has been used to
      correct warfarin-induced coagulopathy. We present our experience with 28 patients
      using FIX complex. METHODS: A retrospective chart review was conducted between
      November 2002 and July 2006 on patients with warfarin-induced coagulopathy. We
      recorded the dose and timing of FIX complex, serial international normalized
      ratios (INRs), early adverse events, and patient outcome. RESULTS: Twenty-eight
      patients met criteria. The mean INR on admission was 5.1, and after FIX complex
      infusion was reduced significantly to 1.9 (P = .008). Eleven patients had a
      repeat INR drawn within 30 minutes after FIX complex infusion. The mean time to
      correction was 13.5 minutes. There were no early thrombotic events or allergic
      reactions. CONCLUSIONS: FIX complex results in an immediate reversal of
      coagulopathy within 15 minutes after administration. Its use should be considered
      as an alternative treatment to fresh-frozen plasma and recombinant Factor VIIa.
      Prospective randomized trials are needed to confirm these findings.

PMID- 18722587
TI  - Nerve growth factor and brain-derived neurotrophic factor attenuate angiotensin
      II-induced facilitation of calcium channels in acutely dissociated nucleus
      tractus solitarii neurons of the rat.
AB  - OBJECTIVE: Neurotrophins, such as nerve growth factor (NGF) and brain-derived
      neurotrophic factor (BDNF), promote neuronal development and neuronal survival,
      but their mechanisms remain controversial. This study aimed to investigate the
      hypothesis that NGF and BDNF interfere with angiotensin-II- and glutamate-induced
      facilitation of voltage-dependent Ca(2+) channels (VDCCs) in nucleus tractus
      solitarius (NTS) neurons. DESIGN: The profile of NGF and BDNF actions in acutely
      dissociated rat NTS was studied using the whole-cell configuration of the patch
      clamp technique. RESULTS: Pretreatment with NGF and BDNF attenuated angiotensin
      II-induced facilitation of VDCCs, but did not attenuate glutamate-induced
      facilitation of the L-type VDCC current in NTS neurons. NGF-induced attenuation
      was antagonised by pretreatment with a tyrosine kinase A (TrkA) receptor
      antagonist K-252a. CONCLUSIONS: NGF attenuated angiotensin-II-induced
      facilitation of L-type VDCCs mediated by TrkA receptors in NTS neurons.

PMID- 18722588
TI  - Fatigue resistance during a voluntary performance task is associated with lower
      levels of mobility in cerebral palsy.
AB  - OBJECTIVES: To investigate muscle fatigue of the knee flexors and extensors in
      people with cerebral palsy (CP) compared with those without motor disability
      during performance of a voluntary fatigue protocol and to investigate the
      relationship with functional mobility. DESIGN: A case-control study. SETTING: A
      biomechanics laboratory. PARTICIPANTS: Ambulatory subjects with CP (n=18; mean
      age, 17.5 y) in Gross Motor Function Classification System (GMFCS) levels I, II,
      and III and a comparison group of age-matched subjects (n=16) without motor
      disability (mean age, 16.6 y). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: The voluntary muscle fatigue protocol consisted of concentric knee
      flexion and extension at 60 degrees a second for 35 repetitions on an isokinetic
      dynamometer. Peak torque for each repetition was normalized by the maximum peak
      torque value. Muscle fatigue was calculated as the rate of decline in normalized
      peak torque across all repetitions, represented by the slope of the linear
      regression. Self-selected and fast gait velocities were measured as well as the
      Pediatric Outcomes Data Collection Instrument (PODCI). RESULTS: Greater
      fatigability (slope) was observed in the comparison group for both knee flexors
      and extensors than in the group with CP. Within CP, lower knee extensor fatigue
      (slope) was associated with lower functioning GMFCS levels and lower levels of
      activity and participation as measured by the PODCI transfers and basic mobility.
      CONCLUSIONS: Even after adjusting for maximum peak torque, the knee flexors and
      extensors of participants with CP were observed to be less fatigable than age
      matched peers without motor disability. The lower rate of muscle fatigue was also
      associated with lower functional mobility in CP. These results may be related to
      strength or activation differences and/or muscle property alterations. Future
      investigations are warranted.

PMID- 18722589
TI  - Self-representation in social anxiety disorder: linguistic analysis of
      autobiographical narratives.
AB  - Cognitive models of social anxiety disorder (SAD) posit aberrant beliefs about
      the social self as a key psychological mechanism that maintains fear of negative
      evaluation in social and performance situations. Consequently, a distorted self
      view should be evident when recalling painful autobiographical social memories,
      as reflected in linguistic expression, negative self-beliefs, and emotion and
      avoidance. To test this hypothesis, 42 adults diagnosed with SAD and 27 non
      psychiatric healthy controls (HC) composed autobiographical narratives of
      distinct social anxiety related situations, generated negative self-beliefs
      (NSB), and provided emotion and avoidance ratings. Although narratives were
      matched for initial emotional intensity and present vividness, linguistic
      analyses demonstrated that, compared to HC, SAD employed more self-referential,
      anxiety, and sensory words, and made fewer references to other people. There were
      no differences in the number of self-referential NSB identified by SAD and HC.
      Social anxiety symptom severity, however, was associated with greater self
      referential NSB in SAD only. SAD reported greater current self-conscious emotions
      when recalling autobiographical social situations, and greater active avoidance
      of similar situations than did HC. These findings support cognitive models of
      SAD, and suggest that autobiographical memory of social situations in SAD may
      influence current and future thinking, emotion, and behavioral avoidance.

PMID- 18722590
TI  - Posterior hippocampal volumes are associated with remission rates in patients
      with major depressive disorder.
AB  - BACKGROUND: The hippocampus (HC) is smaller in patients with recurrent major
      depressive disorder (MDD), but few longitudinal studies have examined whether
      volume is associated with clinically meaningful outcomes such as response to
      treatment. METHODS: We compared regional (head and body/tail) HC volumes in 46
      patients with MDD, 14 of whom remitted after 8 weeks of first treatment to HC
      volumes of 32 patients who were not in remission after 8 weeks. RESULTS: Patients
      who remitted had larger pretreatment hippocampal body/tail volumes bilaterally
      compared with those who were not in remission at 8 weeks. This difference was not
      apparent in either the right or left hippocampal head. CONCLUSIONS: These
      findings extend a small number of previous reports, suggesting that regional
      brain volumes might be associated with rate and extent of clinical response to
      antidepressant medication.

PMID- 18722591
TI  - Decreased cognition in children with risk factors for Alzheimer's disease.
AB  - BACKGROUND: The epsilon4 allele of the apolipoprotein E gene (APOE-epsilon4) and
      a family history (+FH) of Alzheimer's disease (AD) are both risk factors for the
      development of AD. Although studies to identify a preclinical phase of AD have
      led to evidence of APOE-epsilon4- and +FH-related differences in brain and
      cognitive functioning in healthy adults, the relative influence of these factors
      in children is unknown. METHODS: To investigate this issue, school-age children
      (n = 109) received standardized achievement tests, the Rey-Osterrieth Complex
      Figure Test (Copy Condition; RCFT-CC), assessment of family medical history, and
      buccal swab testing to determine their APOE genotype. RESULTS: Analyses revealed
      that, relative to children without these risk factors, children who possess both
      an APOE-epsilon4 allele and a +FH of AD and/or significant memory problems (MP)
      obtained lower scores on nearly every cognitive test administered. CONCLUSIONS:
      Findings suggest that when both AD risk factors are present, cognition may be
      adversely affected as early as childhood. Thus, risk factors for a disorder of
      pathological aging (i.e., AD) may have implications for the etiology of certain
      types of learning difficulties in children.

PMID- 18722592
TI  - Psychosis induced by decreased CD4+ T cell and high viral load in human
      immunodeficiency virus infection: a case report.

PMID- 18722593
TI  - Prospective prediction of posttraumatic stress disorder symptoms using fear
      potentiated auditory startle responses.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) has been most consistently
      associated with exaggerated physiologic reactivity to startling sounds when such
      sounds occur in threatening contexts. There is conflicting evidence about whether
      startle hyperreactivity is a preexisting vulnerability factor for PTSD or an
      acquired result of posttrauma neural sensitization. Until now, there have been no
      prospective studies of physiologic reactivity to startling sounds in threatening
      contexts as predictors of PTSD symptoms. METHODS: One hundred and thirty-eight
      police academy cadets without current psychopathology were exposed to repeated
      106-dB startling sounds under increasing (low, medium, or high) threat of mild
      electric shock while their eye-blink electromyogram, skin conductance, heart
      rate, and subjective fear responses were recorded. Measures of response
      habituation were also calculated. Following 1 year of exposure to police-related
      trauma, these participants were assessed for PTSD symptom severity. RESULTS:
      After accounting for other baseline variables that were predictive of PTSD
      symptom severity (age and general psychiatric distress), more severe PTSD
      symptoms were prospectively and independently predicted by the following startle
      measures: greater subjective fear under low threat, greater skin conductance
      under high threat, and slower skin conductance habituation. CONCLUSIONS: These
      results imply that hypersensitivity to contextual threat (indexed by greater fear
      under low threat), elevated sympathetic nervous system reactivity to explicit
      threat (indexed by larger responses under high threat), and failure to adapt to
      repeated aversive stimuli (evidenced by slower habituation) are all unique
      preexisting vulnerability factors for greater PTSD symptom severity following
      traumatic stress exposure. These measures may eventually prove useful for
      preventing PTSD.

PMID- 18722594
TI  - Vaccination as a novel approach for treating depressive behavior.
AB  - BACKGROUND: Depressive behavior in animals is often associated with reduced
      levels of brain-derived neurotrophic factor (BDNF) and impaired neurogenesis in
      the hippocampus. Recent studies showed that T cells recognizing central nervous
      system (CNS)-specific antigens can regulate adult hippocampal neurogenesis and
      expression of BDNF. On the basis of these findings, we hypothesized that
      controlling CNS specific immune activity by immunization with a myelin-related
      peptide may have an antidepressant effect. METHODS: We investigated the impact of
      immunization with a CNS related peptide, on the behavioral and cellular outcomes
      of chronic mild stress (CMS; an animal model for depression) in rats. RESULTS:
      Immunization with a weak agonist of a myelin-derived peptide ameliorated
      depressive behavior such as anhedonia (measured by sucrose preference), induced
      by CMS in rats. The behavioral outcome was accompanied by restoration of
      hippocampal BDNF levels and neurogenesis. CONCLUSIONS: The results of this study
      introduce a novel approach of immunization with CNS-related antigens as a
      therapeutic means for fighting depression. Vaccination, as an antidepressant
      therapy, may invoke several molecular and cellular pathways that are known to be
      regulated by antidepressant drugs. Therefore, we suggest that immune-based
      therapies should be considered for treatment of depression.

PMID- 18722595
TI  - Characterization of a novel fungal chitosanase Csn2 from Gongronella sp. JG.
AB  - A 28kDa chitosanase designated as Csn2 was purified from the culture broth of the
      fungus Gongronella sp. JG through three chromatography steps: CM-Sepharose FF,
      Superdex 200 and SP-Sepharose FF. Its optimal reaction pH and temperature were pH
      5.6 and between 55 degrees C and 60 degrees C. The half-lives of Csn2 at 50
      degrees C and 55 degrees C were estimated to be 30min and 11min, respectively.
      The K(m) value of Csn2 in sodium acetate buffer (pH 5.6) at 55 degrees C was
      8.86mg/mL. Mn(2+), Ca(2+) and Sr(2+) were activators of Csn2; ETDA was an
      inhibitor. Cu(2+) stimulated Csn2 at 1mM, but inhibited Csn2 activity at 10mM.
      Csn2 displayed strong activity on colloidal chitosan, but did not hydrolyze
      colloidal chitin and carboxylmethyl cellulose. Thin layer chromatography analysis
      showed the end products of colloidal chitosan hydrolyzed by Csn2 were chitobiose,
      chitotriose and chitotetraose with chitotriose as the major product. The N
      terminus of Csn2 was determined to be YQLPANLKKIYDSHKSGTC. Part of the genomic
      DNA sequence corresponding to Csn2 was cloned. Sequence alignment showed DNA
      sequence of Csn2 was partly identical to chitosanase genes from Metarhizium
      anisopliae var. acridum, Hypocrea lixii and Aspergillus fumigatus. Based on
      sequence similarity, Csn2 was classified as a GH-75 chitosanase.

PMID- 18722596
TI  - Stereoselective synthesis of a model alpha-glycoside of the beta-D-ManNAcp-(1-
      >4)-d-Glc disaccharide starting from lactose, avoiding the beta-mannosaminylation
      step.
AB  - A model isopropyl alpha-glycoside of the beta-d-ManNAc-(1-->4)-d-Glc disaccharide
      has been prepared from lactose, avoiding the beta-mannosaminylation step. Three
      complementary approaches involving first the preparation and then the
      glycosidation of beta-thiophenyl donors of the protected disaccharides, (a) beta
      d-ManNAc-(1-->4)-d-Glc, (b) beta-d-TalNAc-(1-->4)-d-Glc and (c) lactose, were
      compared. The best results were obtained employing a suitably protected lactose
      donor, and submitting its alpha-isopropyl glycoside to an amination with
      inversion in position 2' followed by an epimerization at C-4'.

PMID- 18722597
TI  - Rational and mechanistic perspectives on reinforcement learning.
AB  - This special issue describes important recent developments in applying
      reinforcement learning models to capture neural and cognitive function. But
      reinforcement learning, as a theoretical framework, can apply at two very
      different levels of description: mechanistic and rational. Reinforcement learning
      is often viewed in mechanistic terms--as describing the operation of aspects of
      an agent's cognitive and neural machinery. Yet it can also be viewed as a
      rational level of description, specifically, as describing a class of methods for
      learning from experience, using minimal background knowledge. This paper
      considers how rational and mechanistic perspectives differ, and what types of
      evidence distinguish between them. Reinforcement learning research in the
      cognitive and brain sciences is often implicitly committed to the mechanistic
      interpretation. Here the opposite view is put forward: that accounts of
      reinforcement learning should apply at the rational level, unless there is strong
      evidence for a mechanistic interpretation. Implications of this viewpoint for
      reinforcement-based theories in the cognitive and brain sciences are discussed.

PMID- 18722598
TI  - A stochastic model of tumor angiogenesis.
AB  - Angiogenesis is a prerequisite for the growth, invasion and metastasis of solid
      tumors. The aim of this study was to investigate the changes of microvessel
      densities in tumor with a method of probability. We showed that the stages of
      tumor angiogenesis may follow a probabilistic pattern compatible with Markov
      chain and this could be of prognostic importance. The system was simulated with
      10,000 patients in order to show the applicability of this method. This approach
      may improve classification schemes and perhaps make diagnosis and treatment more
      individualized to patients.

PMID- 18722599
TI  - A treatment planning code for inverse planning and 3D optimization in
      hadrontherapy.
AB  - The therapeutic use of protons and ions, especially carbon ions, is a new
      technique and a challenge to conform the dose to the target due to the energy
      deposition characteristics of hadron beams. An appropriate treatment planning
      system (TPS) is strictly necessary to take full advantage. We developed a TPS
      software, ANCOD++, for the evaluation of the optimal conformal dose. ANCOD++ is
      an analytical code using the voxel-scan technique as an active method to deliver
      the dose to the patient, and provides treatment plans with both proton and carbon
      ion beams. The iterative algorithm, coded in C++ and running on Unix/Linux
      platform, allows the determination of the best fluences of the individual beams
      to obtain an optimal physical dose distribution, delivering a maximum dose to the
      target volume and a minimum dose to critical structures. The TPS is supported by
      Monte Carlo simulations with the package GEANT3 to provide the necessary physical
      lookup tables and verify the optimized treatment plans. Dose verifications done
      by means of full Monte Carlo simulations show an overall good agreement with the
      treatment planning calculations. We stress the fact that the purpose of this work
      is the verification of the physical dose and a next work will be dedicated to the
      radiobiological evaluation of the equivalent biological dose.

PMID- 18722600
TI  - Reduced expression of von Hippel-Lindau gene in subjects exposed to
      polychlorinated biphenyls and dibenzofurans.
AB  - Polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) are
      ubiquitous pollutants found in the environment and human tissues. A cohort in
      Taiwan has undergone follow-up for 24 years after exposure to high levels of PCBs
      and PCDFs. The incidence of chloracne, hyperkeratosis, and abnormal nail was
      increased among exposed people. We conducted a study to identify the genes whose
      expressions were affected by such exposure. A cDNA microarray system consisting
      of 908 genes was used for pooled serum samples from non-smoking men exposed to
      PCBs and PCDFs (n=15) and their matched referents (n=15) in triplicate. After
      adjusting for background and housekeeping genes, genes with different expressions
      between the exposure and reference groups were determined by both regression and
      cluster analysis, and further confirmed by real-time RT-PCR. The tumor suppressor
      gene von Hippel-Lindau (VHL) was found to be down-regulated in the microarray
      analysis. VHL gene expression levels were also found to be positively associated
      with age, shown by real-time RT-PCR. Upon age adjustment, VHL gene expression was
      reduced in Yucheng ("oil disease") subjects as compared to referents. Among
      Yucheng people, those with abnormal nails had lower VHL expressions than those
      without abnormal nails. These findings provide new insights into the potential
      role of VHL in health conditions associated with PCB and PCDF exposures.

PMID- 18722602
TI  - Low folate in seminal plasma is associated with increased sperm DNA damage.
AB  - OBJECTIVE: To determine associations between vitamin B status, homocysteine
      (tHcy), semen parameters, and sperm DNA damage. DESIGN: Observational study.
      SETTING: A tertiary referral fertility clinic. PATIENT(S): Two hundred fifty-one
      men of couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm
      injection (ICSI) treatment, with subgroups of fertile (n = 70) and subfertile men
      (n = 63) defined according to semen concentration and proven fertility.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The DNA fragmentation index (DFI)
      as marker of sperm DNA damage determined using the sperm chromatin structure
      assay (SCSA), and semen parameters assessed according to World Health
      Organization criteria; tHcy, folate, cobalamin, and pyridoxine concentrations
      determined in seminal plasma and blood. RESULT(S): In the total group of fertile
      and subfertile men, all biomarkers in blood were statistically significantly
      correlated with those in seminal plasma. No correlation was found between the
      biomarkers in blood and the semen parameters. In seminal plasma, both tHcy and
      cobalamin positively correlated with sperm count. Folate, cobalamin, and
      pyridoxine were inversely correlated with ejaculate volume. In fertile men,
      seminal plasma folate showed an inverse correlation with the DNA fragmentation
      index. CONCLUSION(S): Low concentrations of folate in seminal plasma may be
      detrimental for sperm DNA stability.

PMID- 18722601
TI  - Protein kinase C subtypes and retinal ischemic preconditioning.
AB  - The purpose of our study was to determine the specific subtypes of protein kinase
      C involved in the neuroprotection afforded by retinal ischemic preconditioning
      (IPC), their relationship to the opening of mitochondrial KATP (mKATP) channels,
      and their role in apoptosis after preconditioning and ischemia. Rats were
      subjected to retinal ischemia after IPC, or retinas were rendered ischemic after
      pharmacological opening of mKATP channels. Using immunohistochemistry and image
      analysis, we determined cellular localization of PKC subtypes. We blocked PKC
      delta and -epsilon to study the effect on protection with IPC or with IPC
      mimicking by the opening of mKATP channels. PKC subtypes were inhibited
      pharmacologically or with interfering RNA. Electroretinography assessed
      functional recovery after ischemia. IPC was effectively mimicked by injection of
      diazoxide to open the mKATP channel. IPC and/or its mimicking were attenuated by
      the PKC-delta inhibitor rottlerin and by interfering RNA targeting PKC-delta or 
      epsilon. Using TUNEL staining and Western blotting for caspase-3 and fodrin
      breakdown we assessed apoptosis. The injection of interfering RNA to PKC-delta
      and -epsilon before preconditioning significantly enhanced TUNEL staining as well
      as the cleavage of caspase-3 and fodrin after ischemia. In summary, our
      experiments have shown that both PKC-delta and -epsilon subtypes are involved in
      the cellular signaling that results in neuroprotection from IPC and that both are
      downstream of the opening of mKATP channels.

PMID- 18722603
TI  - Wilms' tumor gene 1 (WT1) overexpression in neurons in deep endometriosis: a
      pilot study.
AB  - Innervation of deep endometriosis has recently been linked to its severe pain
      symptoms. We demonstrated for the first time that the Wilms' tumor gene 1 is
      overexpressed in part of these nerves.

PMID- 18722604
TI  - Induction of peritoneal endometriosis in nude mice with use of human immortalized
      endometriosis epithelial and stromal cells: a potential experimental tool to
      study molecular pathogenesis of endometriosis in humans.
AB  - OBJECTIVE: To determine whether a mixed population of immortalized human
      endometriosis epithelial and stromal cells is able to induce peritoneal
      endometriosis in nude mice. DESIGN: Prospective experimental study. Human
      immortalized endometriosis epithelial and stromal cells were xenografted into
      ovariectomized nude mice. Macroscopically, the number of induced endometriosis
      like lesions and their color were determined. Microscopically, histomorphology of
      endometriosis glands and their structure were analyzed, and comparisons were made
      with tissue from spontaneous endometriosis in women. SETTING: College of
      Veterinary Medicine and Biomedical Sciences, Texas A&M University. ANIMALS: Seven
      ovariectomized nude mice. INTERVENTION(S): Minimal invasive procedures were
      performed to administer estrogen pellets and transplant immortalized human
      endometriosis epithelial and stromal cells into nude mice. MAIN OUTCOME
      MEASURE(S): Peritoneal endometriosis-like lesions induced in nude mice were
      characterized and compared with spontaneous peritoneal endometriosis in women.
      RESULT(S): Xenografts of human immortalized endometriosis epithelial and stromal
      cells into the peritoneal cavity of the recipient nude mice are able to
      proliferate, attach, invade, reorganize, and establish peritoneal endometriosis.
      Endometriosis glands at different stages of growth were present in induced
      endometriosis-like lesions. Proliferating cell nuclear antigen, metalloproteinase
      2, estrogen receptor-alpha, cyclooxygenase-2, and prostaglandin E(2) receptors
      EP2 and EP4 proteins were expressed in both endometriosis glandular epithelial
      and stromal cells of the induced endometriosis-like lesions. CONCLUSION(S): This
      xenograft model could be used as a potential experimental tool to understand the
      molecular and cellular aspects of the pathogenesis of endometriosis in humans.

PMID- 18722605
TI  - Abdominal fat distribution and insulin resistance in Indian women with polycystic
      ovarian syndrome.
AB  - The relationship between insulin resistance and abdominal fat distribution was
      studied in Indian patients with PCOS. Subcutaneous fat, together with a family
      history of type 2 diabetes mellitus, was the best marker of insulin resistance.

PMID- 18722606
TI  - Uterus didelphys with an obstructed unilateral vagina by a transverse vaginal
      septum associated with ipsilateral renal agenesis, duplication of inferior vena
      cava, high-riding aortic bifurcation, and intestinal malrotation: a case report.
AB  - OBJECTIVE: To present a case of mullerian defects associated with other
      anomalies, including ipsilateral renal agenesia, duplication of inferior vena
      cava, high-riding aortic bifurcation, and intestinal malrotation. DESIGN: Case
      study. SETTING: Academic medical center. PATIENT(S): A 16-year-old woman with
      mullerian defects associated with vascular and intestinal anomalies.
      INTERVENTION(S): Excision of vaginal septum. MAIN OUTCOME MEASURE(S): Improvement
      of symptoms caused by obstructed mullerian defect. RESULT(S): After an incision
      on the vaginal septum, a large amount of chocolate-colored fluid was drained, and
      the dimensions of the right uterus were diminished. Then the vaginal septum was
      excised completely; we saw a second distinct cervical portion. CONCLUSION(S):
      Uterus didelphys with obstructed hemivagina is almost always associated with
      renal agenesis ipsilateral to the obstruction. Inferior vena cava duplication
      associated with mullerian anomalies is an extremely rare condition. In addition,
      the presented case also had a high-riding aortic bifurcation and intestinal
      malrotation. To the best of our knowledge, this is the first case to include all
      of these anomalies.

PMID- 18722607
TI  - Degree of hyperinsulinemia, independent of androgen levels, is an important
      determinant of the severity of hirsutism in PCOS.
AB  - OBJECTIVE: To determine whether the severity in hyperandrogenemia determines, to
      a significant degree, the severity of hirsutism in patients with polycystic ovary
      syndrome (PCOS). DESIGN: Cross-sectional study. SETTING: Tertiary care academic
      referral center. PATIENT(S): A total of 749 patients with PCOS. INTERVENTION(S):
      History and physical examination, blood sampling. MAIN OUTCOME MEASURE(S):
      Hirsutism defined by a value of >or=6 using the modified Ferriman-Gallwey (mFG)
      score, age, body mass index (BMI), calculated homeostatic assessment for insulin
      resistance (HOMA-IR) value, and levels of total (TT) and free (FT) testosterone,
      dehydroepiandrosterone sulfate (DHEAS) 17-hydroxyprogesterone (17OH-P), and
      fasting insulin (INS) and glucose (GLC). RESULT(S): Univariate correlations
      revealed associations between the mFG score and INS, 17OH-P, HOMA-IR, and BMI.
      Multivariate classification and regression tree analysis indicated that INS had
      the most significant association with mFG score and that at higher INS levels T
      played an additional role whereas at lower INS levels 17OH-P had an effect;
      however, this model accounted for only 8.2% of total variation in mFG score.
      CONCLUSION(S): Insulin appears to have a direct effect on the severity of
      hirsutism in PCOS and appears to have a synergistic interaction with TT. Notably,
      over 90% of the variation in the mFG score was not related to the factors studied
      and likely reflects intrinsic factors related to pilosebaceous unit function or
      sensitivity and to other factors not yet assessed.

PMID- 18722608
TI  - In vitro culture under physiologic oxygen concentration improves blastocyst yield
      and quality: a prospective randomized survey on sibling oocytes.
AB  - A prospective randomized study was carried on sibling oocytes in which human
      gametes and embryos were cultured at physiologic (6% CO(2) + 5% O(2) + 89% N(2))
      condition from insemination to day 6 or at atmospheric (6% CO(2) in air)
      condition until day 3 and at physiologic environment afterward. The results
      showed that physiologic oxygen concentration throughout culture period improved
      total blastocyst yield and day 5 embryo quality.

PMID- 18722609
TI  - Laparoscopy in women with unexplained infertility: a cost-effectiveness analysis.
AB  - OBJECTIVE: To evaluate the cost effectiveness of laparoscopy for unexplained
      infertility. DESIGN: We performed a cost-effectiveness analysis using a computer
      generated decision analysis tree. Data used to construct the mathematical model
      were extracted from the literature or obtained from our practice. We compared
      outcomes following four treatment strategies: [1] no treatment, [2] standard
      infertility treatment algorithm (SITA), [3] laparoscopy with expectant management
      (LSC/EM), and [4] laparoscopy with infertility therapy (LSC/IT). The incremental
      cost-effectiveness ratio (ICER) was calculated, and one-way sensitivity analyses
      assessed the impact of varying base-case estimates. SETTING: Academic in vitro
      fertilization practice. PATIENT(S): Computer-simulated patients assigned to one
      of four treatments. INTERVENTION(S): Fertility treatment or laparoscopy. MAIN
      OUTCOME MEASURE(S): Incremental cost-effectiveness ratios. RESULT(S): Using base
      case assumptions, LSC/EM was preferred (ICER =$128,400 per live-birth in U.S.
      dollars). Changing the following did not alter results: rates and costs of
      multiple gestations, penalty for high-order multiples, infertility treatment
      costs, and endometriosis prevalence. Outcomes were most affected by patient
      dropout from infertility treatments-SITA was preferred when dropout was less than
      9% per cycle. Less important factors included surgical costs, acceptability of
      twins, and the effects of untreated endometriosis on fecundity. CONCLUSION(S):
      Laparoscopy is cost effective in the initial management of young women with
      infertility, particularly when infertility treatment dropout rates exceed 9% per
      cycle.

PMID- 18722610
TI  - Glucocorticoid receptor-mediated regulation of MMP9 gene expression in human
      ovarian surface epithelial cells.
AB  - OBJECTIVE: To obtain proof-of-concept that locally produced anti-inflammatory
      steroids suppress ovulation-associated extracellular matrix proteases in human
      ovarian surface epithelial (OSE) cells. DESIGN: Primary OSE cell cultures treated
      with interleukin-1alpha (IL-1alpha) (500 pg/mL) as proxy for inflammation,
      with/without anti-inflammatory steroid (cortisol or progesterone [P], 0.01-1.0
      microM). SETTING: Academic medical center. PATIENT(S): Sixteen premenopausal
      women (29-46 years) undergoing surgery for nonmalignant gynecological conditions.
      MAIN OUTCOME MEASURE(S): Semiquantitative extracellular matrix protease gene
      expression profiling with verification by real-time quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) and gelatinase zymography.
      RESULT(S): Treatment with IL-1alpha stimulated messenger RNA (mRNA) expression of
      several ovulation-associated matrix metalloproteinase genes by OSE cell cultures,
      including gelatinase B (MMP9) but not gelatinase A (MMP2). The IL-1alpha
      stimulated MMP9 mRNA production was suppressed by cortisol but not P. Cortisol
      but not P also dose-dependently suppressed IL-1alpha-stimulated MMP9 gelatinase
      activity and this effect was blocked by the glucocorticoid receptor antagonist
      RU486. CONCLUSION(S): In human OSE cells, stimulation of MMP9 gene expression and
      proteolytic activity by IL-1alpha is suppressed by anti-inflammatory cortisol
      through a glucocorticoid receptor-mediated mechanism. Because IL-1alpha also
      generates cortisol formation in OSE by stimulating cortisone reductase activity,
      these results support a role for intracrine cortisol in minimizing proteolytic
      damage to the OSE at ovulation.

PMID- 18722611
TI  - Complete follicular development and recovery of ovarian function of frozen
      thawed, autotransplanted caprine ovarian cortex.
AB  - Frozen-thawed ovarian cortical fragments (1 mm(3)) were autotransplanted to the
      uterus of completely ovariectomized goats. The grafts developed preovulatory
      follicles, accompanied by estrous behavior and a rise in plasma E(2) levels,
      demonstrating successful cryopreservation and transplantation.

PMID- 18722612
TI  - Nerve repair: experimental and clinical evaluation of biodegradable artificial
      nerve guides.
AB  - SUMMARY: Several methods have been used for bridging nerve gaps. Much of the
      focus in nerve repair of peripheral nerves has focussed on creating either
      natural or synthetic tubular nerve guidance channels, as an alternative to nerve
      autografts. These conduits act to guide axons sprouting from the regenerating
      nerve end, provide a conduit for diffusion of neurotrophic and neurotropic
      factors secreted by the injured nerve stump, as well as help protect against
      infiltration of fibrous tissue. Among the conduits that have been studied are
      autogenous veins, arteries, mesothelial chambers, synthetic tubes, collagen
      tubes, amnion tubes, cardiac and skeletal muscle, and silicon tubes. This paper
      briefly reviews major studies in which bioabsorbable nerve guides were used for
      peripheral nerve repair, with a particular emphasis on polymeric guidance
      channels, in an effort to evaluate their use, their ability to support or enhance
      nerve regeneration and any potential problems.

PMID- 18722613
TI  - Orthoplasty in trauma & reconstructive microsurgery: World Society for
      Reconstructive Microsurgery IV WSRM Congress, Athens, Greece.

PMID- 18722614
TI  - Leisure time physical activity during pregnancy and preterm birth in Brazil.
AB  - OBJECTIVE: To investigate the relationship between leisure time physical activity
      (LTPA) during pregnancy and preterm birth. METHODS: A cross-sectional, population
      based study evaluated LTPA during pregnancy in 4147 mothers using data from the
      2004 Pelotas Birth Cohort Study. Gestational age was determined by last menstrual
      period, or when not available, by ultrasound or the Dubowitz method. Type of
      LTPA, length of usual session, and frequency were determined for each trimester.
      RESULTS: A total of 14.6% of all births were considered preterm. Only 13.3% of
      women reported engaging in LTPA during pregnancy. After adjusting for
      confounders, LTPA in all 3 trimesters (prevalence ratio [PR] 0.55; 95% confidence
      interval [CI] 0.32-0.96), LTPA in the third trimester (PR 0.50; 95% CI 0.31
      0.80), and minimum LTPA (> or = 90 min/week) in the third trimester (PR 0.58; 95%
      CI 0.34-0.98) showed a protective association with preterm birth in the adjusted
      analysis. CONCLUSION: LTPA, especially throughout pregnancy and in the third
      trimester, was associated with a lower chance of preterm birth.

PMID- 18722615
TI  - Collagen type 3 alpha 1 polymorphism and risk of pelvic organ prolapse.
AB  - OBJECTIVE: To investigate whether pelvic organ prolapse (POP) is associated with
      collagen 3 alpha 1 (COL3A1) polymorphisms and other factors. METHODS: A case
      control association study was conducted with 84 women affected with POP and 147
      controls. The genotypes of nucleotides COL3A1 rs1800255 and COL3A1 rs1801184
      polymorphisms were ascertained by polymerase chain reaction and restriction
      fragment length polymorphism analysis. RESULTS: The distribution of the COL3A1
      rs1800255 genotypes was significantly different among affected women and
      controls. Older age and incidence of COL3A1 rs1800255 genotype AA were
      significantly associated with risk of POP. CONCLUSION: There may be an
      association between COL3A1 genotype and risk of POP.

PMID- 18722616
TI  - Progesterone receptor gene polymorphisms are not associated with preterm birth in
      a Hispanic population.
AB  - OBJECTIVE: To determine whether increased frequency of mutant alleles of the
      progesterone receptor gene (PGR) was associated with preterm birth in a
      population of Hispanic women. METHODS: Placental DNA from 64 patients who had
      preterm births and 54 control patients was genotyped for 4 progesterone receptor
      gene polymorphisms by polymerase chain reaction (PCR) restriction fragment length
      polymorphism. The chi(2) test and t test were used to calculate statistical
      significance. Linkage disequilibrium was calculated using the Linkage
      Disequilibrium Analyzer program. RESULTS: The genotypic frequencies of the 4
      polymorphisms were not significantly different between the study and control
      groups. In addition, there was complete linkage disequilibrium between V660L,
      H770H, and PROGINS polymorphisms, but not with +331G/A polymorphism. CONCLUSIONS:
      The present study suggests that polymorphisms in the progesterone receptor gene
      are unlikely to be associated with an increased risk of preterm birth in a
      Hispanic population.

PMID- 18722617
TI  - Prevalence and risk factors of irritable bowel syndrome in Korean adolescent
      girls: a school-based study.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional
      gastrointestinal disorders, with a strong female predominance. When compared to
      the vast knowledge pertaining to adults with IBS, very little is known about IBS
      in the adolescent population. In Korea, the field of adolescent health with IBS
      is just beginning to develop, so there is still a lack of information concerning
      the prevalence of IBS in adolescent groups. OBJECTIVES: The purposes of this
      study were to explore the prevalence of IBS among Korean adolescent girls, and
      identify the risk factors affecting IBS occurrence. DESIGN: This study adopted a
      cross-sectional descriptive design using the self-reported questionnaire.
      METHODS: A total of 405 adolescent females were recruited from 5 academic high
      schools in Korea in August and September of 2007. IBS was diagnosed based on the
      Rome II criteria. For the evaluation of risk factors on the IBS, we investigated
      dietary habit, life style, stress, anxiety, depression, and premenstrual syndrome
      (PMS). RESULTS: The prevalence of IBS according to Rome II criteria was 25.7% in
      the subjects. The multivariate logistic regression analyses revealed that higher
      stress (OR 2.25, 95% CI 1.13-4.48), anxiety (OR 4.27, 95% CI 1.09-16.71), and
      depression (OR 10.87, 95% CI 1.14-103.81) were independently associated with
      increased IBS occurrence. CONCLUSIONS: The prevalence of IBS in female adolescent
      students from this study was higher compared with those reported in the Western
      countries. This study provides much need information about the relatively
      unstudied Korean female adolescents in terms of IBS issues and aspects of
      psychological attributes to IBS. This study has the potential to influence the
      development of better promotion programs for adolescents and women's health.

PMID- 18722618
TI  - High dietary menaquinone intake is associated with reduced coronary
      calcification.
AB  - BACKGROUND: Dietary vitamin K is thought to decrease risk of cardiovascular
      disease by reducing coronary calcification, but inconsistent results are
      reported. This may be due to different effects of vitamin K(1) (phylloquinone)
      and vitamin K(2) (menaquinone, MK), but few studies included both. METHODS: We
      investigated the association of intake of phylloquinone and menaquinone,
      including its subtypes (MK4-MK10), with coronary calcification in a cross
      sectional study among 564 post-menopausal women. Phylloquinone and menaquinone
      intake was estimated using a food-frequency questionnaire. RESULTS: Sixty-two
      percent (n=360) of the women had coronary calcification based on 1.5-mm thick
      slices. Phylloquinone intake was not associated with coronary calcification with
      a relative risk (RR) of 1.17 (95%-confidence interval: 0.96-1.42; p(trend)=0.11)
      of the highest versus lowest quartile. Menaquinone intake was associated with
      decreased coronary calcification with an RR of 0.80 (95%-CI: 0.65-0.98;
      p(trend)=0.03). CONCLUSION: This study shows that high dietary menaquinone
      intake, but probably not phylloquinone, is associated with reduced coronary
      calcification. Adequate menaquinone intakes could therefore be important to
      prevent cardiovascular disease.

PMID- 18722619
TI  - Biomechanical effect of mineral heterogeneity in trabecular bone.
AB  - Due to daily loading, trabecular bone is subjected to deformations (i.e.,
      strain), which lead to stress in the bone tissue. When stress and/or strain
      deviate from the normal range, the remodeling process leads to adaptation of the
      bone architecture and its degree of mineralization to effectively withstand the
      sustained altered loading. As the apparent mechanical properties of bone are
      assumed to depend on the degree and distribution of mineralization, the goal of
      the present study was examine the influences of mineral heterogeneity on the
      biomechanical properties of trabecular bone in the human mandibular condyle. For
      this purpose nine right condyles from human dentate mandibles were scanned and
      evaluated with a microCT system. Cubic regional volumes of interest were defined,
      and each was transformed into two different types of finite element (FE) models,
      one homogeneous and one heterogeneous. In the heterogeneous models the element
      tissue moduli were scaled to the local degree of mineralization, which was
      determined using microCT. Compression and shear tests were simulated to determine
      the apparent elastic moduli in both model types. The incorporation of
      mineralization variation decreased the apparent Young's and shear moduli by
      maximally 21% in comparison to the homogeneous models. The heterogeneous model
      apparent moduli correlated significantly with bone volume fraction and degree of
      mineralization. It was concluded that disregarding mineral heterogeneity may lead
      to considerable overestimation of apparent elastic moduli in FE models.

PMID- 18722620
TI  - Motor unit acceleration maps and interference mechanomyographic distribution.
AB  - The study analyses the two-dimensional distribution of surface mechanomyographic
      (MMG) signal generated by the activation of single motor units located in three
      transverse positions in the tibialis anterior muscle. In 12 healthy volunteers,
      surface MMG signals were recorded from the tibialis anterior muscle with a 3 x 4
      grid of accelerometers spaced by 20 and 30 mm in the transverse and longitudinal
      direction. Three intramuscular electromyographic (EMG) signals were recorded with
      wire electrodes inserted 20-mm apart, between the first and second most proximal
      accelerometers of each column of the grid. The subject was asked to activate
      three different motor units (target motor units) in three contractions with
      visual feedback from each of the three intramuscular recordings (three
      locations). The MMG signals from the 12 accelerometers were averaged using the
      intramuscular single motor unit action potentials as trigger in order to obtain
      surface motor unit acceleration maps (MUAMs). The peak-to-peak value of the
      averaged MMG depended on motor unit location (P<0.001) and on the transverse
      position of the accelerometer in the grid (P<0.05). Moreover, MUAM amplitude
      depended on the interaction between motor unit location and transverse
      accelerometer position (P<0.05), demonstrating an influence of motor unit
      location on the generated MUAM. The observed dependency of MUAMs on motor unit
      location provides a quantitative analysis of the effect of the volume conductor
      on the recorded surface MMG signal.

PMID- 18722621
TI  - Preparation of a novel light-sensitive copolymer and its application in recycling
      aqueous two-phase systems.
AB  - Aqueous two-phase systems (ATPSs) are potential bioseparation techniques in
      industry. However, a key problem is that aqueous two-phase systems could not be
      effectively recycled to result in high cost and environment pollution. Recently,
      how to prepare recycling copolymers forming aqueous two-phase systems is focused
      on in the area. In this study, a light-sensitive copolymer (P(NNC)) was
      synthesized by using N-isopropylacrylamide (NIPA), N-vinyl-2-pyrrolidone (NVP),
      chlorophyllin sodium copper salt (CHL) as monomers. The copolymer P(NNC) can form
      ATPSs with another novel pH-sensitive copolymer (P(ADB)) which was synthesized by
      co-worker in our laboratory. Over 98% of the P(NNC) copolymer could be recovered
      by using laser radiation at 488 nm. The copolymer P(ADB) could be recovered by
      adjusting the isoelectric point (pI) to 4.1, with a recovery of 97%. Bovine serum
      albumin (BSA) and Tyr were partitioned in the P(NNC)-P(ADB) aqueous two-phase
      systems to examine the systems. It was found that partition coefficient of BSA
      and L-Tyr could reach 4.1 and 0.12 in the systems, respectively.

PMID- 18722622
TI  - Robustness of virus removal by protein A chromatography is independent of media
      lifetime.
AB  - The robustness of virus clearance with respect to protein A media reuse was
      demonstrated using media with four matrix chemistries: Protein A immobilized
      ProSep A, Poros A50, Protein A ceramic Hyper DF and MabSelect SuRe, an alkali
      resistant protein A ligand. Endogenous retrovirus clearance, step yield, impurity
      clearance and other performance parameters were evaluated periodically in media
      cycled up to 300 times. Media lifetime was generally limited by either declining
      step yield or media fouling. However, clearance of endogenous retrovirus remained
      in an acceptable range, either increasing or remaining constant. Multiply cycled
      media were tested for clearance of three viruses (SV40, X-MuLV, and MMV);
      clearance was comparable to naive media. Overall, virus clearance by protein A
      chromatography appears to be extremely robust with respect to media age.

PMID- 18722623
TI  - Toward a full characterization of native starch: separation and detection by size
      exclusion chromatography.
AB  - The structure of starch molecules is relevant to nutrition and industrial
      applications. Size-exclusion chromatography (SEC, also known as GPC) of native
      starch generally suffers non-satisfactory repeatability and reproducibility of
      the dissolution and separation. This work combines two polar organic solvents:
      dimethylsulfoxide for complete dissolution and dimethylacetamide to limit shear
      degradation. The separation is as repeatable as that of polystyrene standards
      performing dissolution and separation at 80 degrees C. Successful covalent
      labeling on the glucose unit is claimed to be published here for the first time
      in non-degradative conditions and allows the use of UV detector with
      significantly higher sensitivity than with a refractometer.

PMID- 18722624
TI  - Modeling wall effects in capillary electrochromatography.
AB  - A volume averaging technique for modeling electroosmotic and pressure driven flow
      in microchannels is applied to a packed capillary electrochromatography column.
      This model can be applied to fluid flow in both porous and open channels and can
      account for porosity variation in the column due to packing and zeta potential
      mismatches between the wall and the packing material. Numerical results are
      presented and compared with experimental results from the literature. Several
      different porosity models are shown to produce similar concentration profiles and
      allow the model to reproduce wall effects observed in experimental columns.

PMID- 18722625
TI  - Capillary rise of a meniscus with phase change.
AB  - The Lucas-Washburn equation, describing the motion of a liquid body in a
      capillary tube, is extended to account for the effect of phase change -
      evaporation or condensation. The system is found to always possess a stable
      equilibrium state when the temperature jump across the interface is confined to a
      certain range. We show that phase change affects the equilibrium height of the
      meniscus, the transition threshold from monotonic to oscillatory dynamics, and
      the frequency of oscillations, when present. At higher mass transfer rates and/or
      large capillary radii, vapor recoil is found to be the dominant factor.
      Evaporation lowers the equilibrium height, increases the oscillation frequency
      and lowers the transition threshold to oscillations. For condensation, two
      regimes are identified: at high mass transfer rates similar trends to those of
      evaporation are observed, whereas the opposite is found for low mass transfer
      rates, resulting in an increased equilibrium height, lower oscillation
      frequencies and a shift of the transition threshold toward monotonic dynamics.

PMID- 18722626
TI  - Aggregation and adsorption properties of sodium dodecyl sulfate in water
      acetamide mixtures.
AB  - The critical micelle concentration (cmc) of sodium dodecyl sulfate was determined
      in water + acetamide media from 0 to 70 wt% of acetamide and at temperatures in
      the range from 20 to 40 degrees C by using conductance, surface tension, and
      fluorescence methods. The cmc increases with increase in acetamide concentration
      and the reported [M.S. Akhter, Colloids Surf. A 121 (1997) 103] decrease in cmc
      was not observed. The limiting surface tension at the cmc does not have any
      dependence on the amount of acetamide added. The cmc data as a function of
      temperature were used to estimate the free energy, enthalpy, and entropy terms
      for micellization. Enthalpy-entropy compensation takes place during
      micellization. Counterion binding constant, surface excess, and aggregation
      number of SDS decrease with increasing acetamide concentration and become almost
      constant for weight percentages of acetamide greater or equal to 30. Pyrene
      appears to move from the interior of the SDS micelle to the micellar interface at
      about 30 wt% acetamide. The empirical relations reported by Aguiar et al. [J.
      Aguiar, P. Carpena, J.A. Molina-Bolivar, C. Carnero Ruiz, J. Colloid Interface
      Sci. 258 (2003) 116] between the parameters of a sigmoid-type expression for the
      ratio of fluorescence emission intensities of pyrene and surfactant properties
      are found to be applicable to SDS in water + acetamide medium below 20 wt%
      acetamide only. Standard free energy of micellization has linear correlations
      with reciprocal of dielectric constant and Gordon parameter of the solvent. The
      water + acetamide medium behaves similar to mixed solvents containing water and
      any polar liquid nonaqueous solvent and this study highlights the significance of
      solvophobicity.

PMID- 18722627
TI  - Attentional retraining: a randomized clinical trial for pathological worry.
AB  - OBJECTIVE: Research has consistently shown that highly anxious individuals tend
      to show an attentional bias in favor of threat cues (i.e., a threat bias).
      Further, recent evidence suggests that it is possible to modify patterns of
      attention allocation for such stimuli and the resulting changes in attention
      allocation alter affective responses to stress. However, to date such changes in
      patterns of attention have been shown only over brief time intervals and only in
      non-anxious individuals who lack a pre-existing attentional bias. In contrast,
      the present study tested the efficacy of such attentional training in a sample of
      severe worriers over an extended period of time using psychometrically validated
      measures of anxiety and depression. METHOD: Twenty-four adult participants
      reporting severe worry were randomly assigned to receive five sessions of either
      computer-delivered attentional retraining or sham training. The study was
      conducted from January to August 2001 and June to August 2002. RESULTS:
      Significant Treatment Group X Time interactions were found for both threat bias
      (p=001) and a composite measure of anxious and depressive symptoms (p=.002).
      Compared to sham-training, the active retraining program produced significant
      reductions in both threat bias and symptoms. CONCLUSIONS: These data support the
      view that an attentional bias in favor of threat cues is an important causal
      factor in generalized anxiety and suggest that a computer-based attentional
      retraining procedure may be an effective component of treatment.

PMID- 18722628
TI  - Facial onset sensory and motor neuronopathy (FOSMN) syndrome responding to
      immunotherapies.
AB  - We report the first non-Caucasian case of facial onset sensory and motor
      neuronopathy (FOSMN) syndrome partially responding to various immunotherapies. A
      55-year-old man had first felt paresthesia on his right cheek at age 45. This
      gradually extended to the scalp. Paresthesia of bilateral fingers and dysphagia
      appeared 6 years later. On admission, facial sensory impairment and bulbar palsy
      were found. There were no sensory or motor deficits evident in any limb, except
      for decreased deep tendon reflex and vibratory sensation. Videofluorography (VF)
      revealed decreased pharyngeal clearance. The sensory nerve action potential
      (SNAP) amplitudes of median and ulnar nerves were decreased. Intravenous
      immunoglobulin therapy and plasma exchange ameliorated his dysesthesia and
      dysphagia after several weeks, and resulted in improvements in VF and SNAP
      abnormalities. These observations suggest that FOSMN syndrome maybe, in part,
      immune-mediated.

PMID- 18722629
TI  - Pessin award lecture 2008: lessons from the Stroke PROTECT program.
AB  - A large proportion of ischemic stroke and transient ischemic attack patients do
      not receive prompt and appropriate treatment with evidence-based, guideline
      recommended, vascular risk reduction therapies when exposed to traditional care.
      Consequently, implementing effective strategies that can bolster the use of
      proven preventive therapies among persons with established cerebrovascular
      disease remains an important goal. The Stroke PROTECT (Preventing Recurrence Of
      Thromboembolic Events through Coordinated Treatment) program, which
      systematically implements 8 medication and behavioral secondary prevention
      measures, was significantly associated with increased treatment utilization at
      hospital discharge, as well as greater adherence, target biomarker control, and
      better clinical outcomes in the post-discharge setting. This award lecture paper
      presents the background, rationale, results, limitations and future directions of
      the original PROTECT program, depicts the progress and preliminary data from
      ongoing national and international PROTECT-based programs, and suggests potential
      next steps in the development and implementation of more empirically derived
      models geared at bridging the stroke prevention knowledge-evidence-practice
      chasm.

PMID- 18722630
TI  - Intravenous thrombolysis followed by intra-arterial thrombolysis and mechanical
      thrombectomy for the treatment of pediatric ischemic stroke.
AB  - Experience with systemic or selective local administration of thrombolytic agents
      in pediatric ischemic stroke is limited to sporadic case reports, since patients
      of age less than 18 years were systematically excluded from randomised controlled
      trials. We report a case of childhood IS attributable to the terminal internal
      carotid artery occlusion that was treated successfully with mechanical
      thrombectomy which followed unsuccessful attempts to recanalize the artery with
      intravenous and intra-arterial thrombolytics. Combined systemic and intra
      arterial thrombolysis followed by mechanical thrombectomy can be feasible and may
      be considered as means of achieving reperfusion in pediatric ischemic stroke
      patients with persisting arterial occlusion.

PMID- 18722631
TI  - Tadalafil administered once daily for lower urinary tract symptoms secondary to
      benign prostatic hyperplasia: a dose finding study.
AB  - PURPOSE: Phosphodiesterase type 5 inhibitors are widely used to treat erectile
      dysfunction. Preliminary data have suggested phosphodiesterase type 5 inhibitor
      efficacy in men with lower urinary tract symptoms associated with clinical benign
      prostatic hyperplasia. MATERIALS AND METHODS: After a 4-week placebo run-in
      period 1,058 men with benign prostatic hyperplasia lower urinary tract symptoms
      were randomly allocated to receive 12-week, once daily treatment with placebo or
      tadalafil (2.5, 5, 10 or 20 mg). RESULTS: The International Prostate Symptom
      Score least squares mean change from baseline to end point was significantly
      improved for 2.5 (-3.9, p = 0.015), 5 (-4.9, p <0.001), 10 (-5.2, p <0.001) and
      20 mg (-5.2, p <0.001) tadalafil compared to placebo (-2.3). International
      Prostate Symptom Score improvements at 4, 8 and 12 weeks were significant for all
      tadalafil doses and they demonstrated a dose-response relationship. Tadalafil
      (2.5 mg) significantly improved the International Prostate Symptom Score
      obstructive subscore and the International Index of Erectile Function-Erectile
      Function domain, the latter in sexually active men with a history of erectile
      dysfunction. Statistically significant improvements were noted for 5, 10 and 20
      mg tadalafil compared to placebo, as assessed by the International Prostate
      Symptom Score irritative and obstructive subscores, International Prostate
      Symptom Score Quality of Life, Benign Prostatic Hyperplasia Impact Index
      (nonsignificant for 10 mg), Global Assessment Question and International Index of
      Erectile Function-Erectile Function domain. No statistically significant effect
      of treatment compared to placebo was noted for peak flow at any tadalafil dose.
      Treatment emergent adverse events were infrequent in all tadalafil groups.
      CONCLUSIONS: Once daily tadalafil demonstrated clinically meaningful and
      statistically significant efficacy and it was well tolerated in men with benign
      prostatic hyperplasia lower urinary tract symptoms. Of the doses studied 5 mg
      tadalafil appeared to provide a positive risk-benefit profile.

PMID- 18722632
TI  - Identification of a 4-coumarate:CoA ligase gene family in the moss,
      Physcomitrella patens.
AB  - Since the early evolution of land plants from primitive green algae,
      phenylpropanoid compounds have played an important role. In the biosynthesis of
      phenylpropanoids, 4-coumarate:CoA ligase (4CL; EC 6.2.1.12) has a pivotal role at
      the divergence point from general phenylpropanoid metabolism to several major
      branch pathways. Although higher plant 4CLs have been extensively studied, little
      information is available on the enzymes from bryophytes. In Physcomitrella
      patens, we have identified a 4CL gene family consisting of four members, taking
      advantage of the available EST sequences and a draft sequence of the P. patens
      genome. The encoded proteins of three of the genes display similar substrate
      utilization profiles with highest catalytic efficiency towards 4-coumarate.
      Interestingly, the efficiency with cinnamate as substrate is in the same range as
      with caffeate and ferulate. The deduced proteins of the four genes share sequence
      identities between 78% and 86%. The intron/exon structures are pair wise similar.
      Pp4CL2 and Pp4CL3 each consists of four exons and three introns, whereas Pp4CL1
      and Pp4CL4 are characterized each by five exons and four introns. Pp4CL1, Pp4CL2
      and Pp4CL3 are expressed in both gametophore and protonema tissue of P. patens,
      unlike Pp4CL4 whose expression could not be demonstrated under the conditions
      employed. Phylogenetic analysis suggests an early evolutionary divergence of
      Pp4CL gene family members. Using Streptomyces coelicolor cinnamate:CoA ligase
      (ScCCL) as an outgroup, the P. patens 4CLs are clearly separated from the
      spermatophyte proteins, but are intercalated between the angiosperm 4CL class I
      and class II. A comparison of three P. patens subspecies from diverse
      geographical locations shows high sequence identities for the four 4CL isoforms.

PMID- 18722633
TI  - A link between chronic sleep restriction and obesity: methodological
      considerations.
AB  - Emerging evidence suggests that chronic sleep restriction contributes to obesity.
      Targeting short sleep duration may therefore offer a novel and effective method
      of preventing and treating obesity. However, this area of research is only in its
      infancy, and a complete understanding of how chronic sleep restriction and
      obesity are linked is currently lacking. The aim of this paper is to briefly
      review epidemiological evidence for an association between chronic sleep
      restriction and obesity in adults, and outline the key methodological limitations
      of these studies. Particular attention is paid to the methods used to measure
      sleep and obesity, as well as the need to control for potential confounding
      variables. Methodological recommendations are provided for future studies that
      will facilitate a more complete understanding of how chronic sleep restriction
      and obesity are linked in the general population. This has implications for the
      development of public health programmes that target sleep as a modifiable risk
      factor for obesity.

PMID- 18722635
TI  - Measurement of elastic nonlinearity using remote laser ultrasonics and CHeap
      Optical Transducers and dual frequency surface acoustic waves.
AB  - A nonlinear ultrasonic technique for evaluating material elastic nonlinearity has
      been developed. It measures the phase modulation of a high frequency (82MHz)
      surface acoustic wave interacting with a low frequency (1MHz) high amplitude
      stress inducing surface acoustic wave. A new breed of optical transducers has
      been developed and used for the generation and detection of the high frequency
      wave. The CHeap Optical Transducer (CHOT) is an ultrasonic transducer system,
      optically activated and read by a laser. We show that CHOTs offer advantages over
      alternative transducers. CHOTs and nonlinear ultrasonics have great potential for
      aerospace applications. Results measuring changes in ultrasonic velocity
      corresponding to different stress states of the sample are presented on fused
      silica and aluminium.

PMID- 18722634
TI  - The method of mouse embryoid body establishment affects structure and
      developmental gene expression.
AB  - To investigate formation of the three primary germ layers in mouse embryoid
      bodies (EBs), we observed changes in structure and gene expression over a 7-day
      culture period. We compared these changes using two methods for EB formation:
      hanging drop (HD) and static suspension culture (SSC). Light microscopy showed
      that a stratified columnar epithelial layer developed on the surface of EBs
      formed using the HD method. From Day 3 in culture, ultrastructural changes
      occurred in the aligned cellular membranes. Condensation of actin filaments was
      followed by formation of complicated adherent junctions and dilatation of
      intercellular canaliculi containing well-developed microvilli. These changes were
      more marked in EBs formed by the HD method than the SSC method. On Day 5 of
      culture, Brachyury gene expression, a marker for mesoderm formation, was detected
      only with the HD method. Nestin, an ectoderm marker, and Foxa2, an endoderm
      marker, were expressed with both methods. These results suggest that in EBs
      formed with the HD method, actin formation and Brachyury gene expression mark the
      transition from two to three primary germ layers. Additionally, the HD method
      promotes more rapid and complete development of mouse EBs than does the SSC
      method. While the SSC method is simple and easy to use, it needs improvement to
      form more complete EBs.

PMID- 18722636
TI  - Non-heparan sulfate GAG-dependent infection of cells using an adenoviral vector
      with a chimeric fiber conserving its KKTK motif.
AB  - Recently, the potential involvement of the putative heparan sulfate proteoglycans
      (HSPG) binding motif, KKTK, in mediating HAdV-5 liver cell infection following
      intravascular virus delivery has been debated. In the present study, we
      demonstrated that HSPGs were not involved in the in vitro infection process of an
      adenoviral vector harboring chimeric fibers without mutation in the KKTK motif,
      HAdV-5-F2/BAdV-4. The entry of HAdV-5-F2/BAdV-4 into cells occurs by two
      mechanisms 1) the attachment of HAdV-5-F2/BAdV-4 to the surface of cells requires
      N-glycosylation, 2) the uptake of the virus is effective after interaction with a
      co-receptor, putatively the chondroitin sulfate C. Together, these results
      contribute to improving our understanding of the molecular mechanisms determining
      HAdV's infectivity in vitro and may aid in designing novel HAdV-based vectors for
      gene therapy applications.

PMID- 18722637
TI  - Kinetics of nitrate and perchlorate reduction in ion-exchange brine using the
      membrane biofilm reactor (MBfR).
AB  - Several sources of bacterial inocula were tested for their ability to reduce
      nitrate and perchlorate in synthetic ion-exchange spent brine (30-45 g/L) using a
      hydrogen-based membrane biofilm reactor (MBfR). Nitrate and perchlorate removal
      fluxes reached as high as 5.4 g Nm(-2)d(-1) and 5.0 g ClO(4)m(-2)d(-1),
      respectively, and these values are similar to values obtained with freshwater
      MBfRs. Nitrate and perchlorate removal fluxes decreased with increasing salinity.
      The nitrate fluxes were roughly first order in H(2) pressure, but roughly zero
      order with nitrate concentration. Perchlorate reduction rates were higher with
      lower nitrate loadings, compared to high nitrate loadings; this is a sign of
      competition for H(2). Nitrate and perchlorate reduction rates depended strongly
      on the inoculum. An inoculum that was well acclimated (years) to nitrate and
      perchlorate gave markedly faster removal kinetics than cultures that were
      acclimated for only a few months. These results underscore that the most
      successful MBfR bioreduction of nitrate and perchlorate in ion-exchange brine
      demands a well-acclimated inoculum and sufficient hydrogen availability.

PMID- 18722638
TI  - The effect of bed age and shear stress on the particle morphology of eroded
      cohesive river sediment in an annular flume.
AB  - Erosion experiments were conducted in an annular flume to determine the effect of
      bed age and shear stress on the particle morphology (fractal dimensions D, D(1),
      and D(k)) of eroded cohesive river sediment. Sediment beds were deposited under
      low shear and left to consolidate for one, two and seven days. Fractal data and
      photomicrographs show particle morphology changed with shear stress and bed age.
      During the one-day experiment, flocs were highly branched and particle geometry
      became more complex with increasing shear. Microflocs present in suspension at
      low shear, formed larger more loosely bound flocs at moderate shear due to
      flocculation. At higher shear, larger flocs were less prevalent due to particle
      breakup. As bed age increased, less sediment was eroded and particles appeared
      less porous and more angular in shape for a given shear stress. Changes in floc
      morphology and eroded sediment mass at various shear stresses may be related to
      bed age-associated biostabilization of bed deposits.

PMID- 18722639
TI  - A long-term performance test on an autotrophic denitrification column for
      application as a permeable reactive barrier.
AB  - The long-term performance of a sulfur-based reactive barrier system was evaluated
      using autotrophic denitrification in a large-scale column. A bacterial
      consortium, containing autotrophic denitrifiers attached on sulfur particles,
      serving as an electron donor, was able to transform 60 mg N L(-1) of nitrate into
      dinitrogen. In the absence of phosphate, the consortium was unable to remove
      nitrate, but after the addition of phosphate, nitrate removal was readily
      evident. Once the column operation had stabilized, seepage velocities of 1.0 x
      10(-3) and 0.5 x 10(-3)cms(-1), corresponding to hydraulic residence times of 24
      and 48 h, respectively, did not affect the nitrate removal efficiency, as
      determined by the nitrate concentration in the effluent. However, data on the
      nitrate, nitrite and sulfate distribution along the column indicated differential
      transformation patterns with column depths. Based on the dinitrogen concentration
      in the total gas collected, the denitrification efficiency of the tested column
      was estimated to be more than 95%. After 500 d operation, the hydrodynamic
      characteristics of the column slightly changed, but these changes did not inhibit
      the nitrate removal efficiency. Data from a bacterial community analysis obtained
      from four parts of the column demonstrated the selective a spatial distribution
      of predominant species depending on available electron acceptors or donors.

PMID- 18722640
TI  - Cadmium stress alters gene expression of DNA mismatch repair related genes in
      Arabidopsis seedlings.
AB  - Cadmium (Cd) is a non essential element, and is a widespread environmental
      pollutant. Exposure to Cd can result in a variety of adverse health effects in
      plant and humans. In the current study, Arabidopsis seedlings were used as a bio
      indicator of Cd pollution. Seedlings were grown on MS media containing 0-6.0 mg
      L(-1) Cd for 18 days, and the gene expression patterns were used to link
      increased Cd exposure with progressive biological effects. Reduction of total
      soluble protein content in shoots of the Arabidopsis seedlings occurred with
      increase in Cd concentrations. For the gene expression patterns, seven genes
      known to be involved in cell division and DNA mismatch repair (MMR) system were
      investigated by semi-quantitative RT-PCR, and normalized using 18S rRNA gene
      expression. Expression of the proliferating cell nuclear antigen 2 (atPCNA 2),
      MutS 3 homolog (atMSH 3) and MutL1 homolog (atMLH1) genes in shoots of
      Arabidopsis was strongly induced by exposure to 0.75 mg L(-1) Cd, but were
      repressed by other Cd concentrations whereas exposure to 0.75-6 mg L(-1) of Cd
      resulted in a decreased expression of atPCNA1, atMSH 2, 6 and 7 genes
      independently of any observable biological effects, including survival, fresh
      weight and chlorophyll level of shoots. This work demonstrated that specific gene
      expression changes could serve as useful molecular biomarkers indicative of Cd
      exposure and related biological effects.

PMID- 18722641
TI  - Biogenic cements from rice hull ash doped with aluminum and iron.
AB  - This work describes the use of rice hull as starting material for the synthesis
      of cements doped with iron and aluminum. Rice hull contains about 10-20% of
      silica along with organic material. In many countries rice hull represents an
      environmental problem since this material is merely burned at rice fields,
      rendering suspended silica particles in the air. Dicalcium silicate (beta
      Ca(2)SiO(4)) is the second most important component of Portland cement and
      presents many environmental advantages over commercial cement. It can be prepared
      at lower temperatures saving energy and raw-materials. In this work we describe
      the synthesis beta-Ca(2)SiO(4) using silica derived from rice hull ash. Silica
      was obtained from heating rice hull at 600 degrees C. Starting materials (silica,
      calcium oxide, barium chloride, iron or aluminum oxide) were weighed in
      stoichiometric proportions and aqueous dispersions having water:solid ratio of
      approximately 20:1 were prepared and treated in an ultrasonic bath for 60 min.
      After this, an intermediate silicate and the excess of calcium hydroxide were
      obtained. Finally solids were dried, grounded and heated up to 800 degrees C. It
      was observed that beta-Ca(2)SiO(4) was obtained when dopant concentration was
      limited to 1%.

PMID- 18722642
TI  - Effect of complexation with humic substances on diffusion of metal ions in water.
AB  - Most studies on diffusion of metal ions in various water-rock systems have dealt
      with free ions (hydrated ions). However, it is often the case that metal ions are
      dissolved as complexed species such as with humic substances (HS) in natural
      waters. Hence, we need to study the diffusion behavior of these complexes in
      order to understand fully the diffusion phenomenon in natural. In this study, the
      diffusion coefficients of free metal ions (M(z+)) and their complexes with HS (M
      HS) were compared to understand the effect of complexation with HS on the
      diffusion of metal ions such as Co(2+), Cd(2+), and rare earth elements
      (REE(3+)). Although the diffusion coefficients of free metal ions depend on ionic
      potential, such dependence was not observed in the presence of HS. Comparing the
      diffusion coefficients of metal complexes with ethylenediaminetetraacetate
      (EDTA), fulvic acid, and humic acid showed that the molecular weight (MW), or the
      size of the ligand, is of primary importance for the diffusion of M-HS. As a
      consequence, the diffusion coefficients of all REE(3+) were similar in the
      presence of HS, while they were different in the absence of HS due to the
      different size of each REE(3+). The similarity among the diffusion coefficients
      of REE-HS was caused by the much larger size of HS compared with each ion.
      However, the distribution coefficients of M-HS were not similar among REE(3+),
      Cd(2+), and Co(2+). REE(3+) and Cd(2+) which have higher affinities for larger MW
      fraction in HS diffused slower than Co(2+) which favors smaller MW fraction. The
      results show that the affinity for different MW fractions among HS controls the
      diffusion of M-HS, which must be important to predict precisely the diffusion
      behavior of metal ions bound to HS in natural systems.

PMID- 18722643
TI  - Comparison of analytical techniques for the determination of aldehydes in test
      chambers.
AB  - The level of carbonyl compounds in indoor air is crucial due to possible health
      effects and the high prevalence of their potential sources. Therefore, selecting
      a convenient and rapid analytical technique for the reliable detection of
      carbonyl compound concentrations is important. The acetyl acetone (acac) method
      is a widely used standard procedure for detecting gaseous formaldehyde. For
      measuring formaldehyde along with other carbonyl compounds, the DNPH-method is
      commonly applied. The recommended procedure for measuring volatile organic
      compounds (VOCs) is sampling on Tenax TA, followed by thermal desorption and
      GC/MS analysis. In this study, different analytical techniques for the
      quantification of formaldehyde, pentanal, and hexanal are critically compared. It
      was found that the acac- and DNPH-method are in very good agreement for
      formaldehyde. In contrast, the DNPH-method significantly underestimates indoor
      air concentrations of the higher aldehydes in comparison to sampling on Tenax TA,
      although both methods are strongly correlated. The reported results are part of
      the EURIMA-WKI study on levels of indoor air pollutants resulting from
      construction, building materials and interior decoration.

PMID- 18722644
TI  - Levels of polychlorinated biphenyls (PCB) and polychlorinated dibenzo-p-dioxins
      and dibenzofurans (PCDD/F) in fillets of farmed Southern Bluefin Tuna (Thunnus
      maccoyii).
AB  - Southern Bluefin Tuna (SBT) (Thunnus maccoyii) is the only farmed tuna species in
      the southern hemisphere, with production centred offshore of Port Lincoln, South
      Australia. SBT farming is a quota-based fishery where farmers fatten wild-caught
      stock for subsequent sale as fresh-chilled or frozen product, mainly to Japanese
      markets. Fillets from wild-caught and farmed SBT were analysed and the
      concentration of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p
      dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are reported for the
      first time. Time of farming was separated into two periods: a typical farming
      period of approximately five months and an experimental scenario that involved
      holding (farming) these fish for an additional 12 months. WHO-PCB and WHO-PCDD/F
      TEQ concentrations in fillets on a fresh weight basis at the same times and over
      the same periods were, 0.67-1.18pg-TEQg(-1) and 0.16-0.29pg-TEQg(-1),
      respectively. All WHO-PCB congeners, and only three WHO-PCDD/F congeners, were
      found to biomagnify during farming, after blank correction. Caution should be
      exercised when extrapolating these results to SBT farming as a whole because of
      the use of varying husbandry and feeding practices employed by different
      companies.

PMID- 18722645
TI  - Integrated research on subsurface environments in Asian urban areas.
AB  - The RIHN project "Human impacts on urban subsurface environments" aims to suggest
      improved development plans of urban centers for human well-being. This will be
      done by examining reconstructed past changes in urban environments, and by
      developing integrated nature-social models. Subsurface environmental indicators
      are developed from the points of view of: (1) human activities; (2) climate
      change; and (3) character of urban development and social policies. Water, heat,
      and material environments and transport vectors are being evaluated by a number
      of different approaches. Some of these include investigating changes in
      groundwater resources using satellite observations, reconstructing effects of
      climate change and urbanization using subsurface thermal regimes, and evaluating
      past contamination patterns from preserved subsurface records. In this overview
      paper, we describe the current status of urbanization in Asia, subsurface water
      conditions, material and contaminant transport to surface waters by groundwater,
      and subsurface thermal anomalies due to the heat island effect. The rapid pace of
      urbanization in Asia requires that we develop a better understanding of how to
      deal with environmental impacts, both above and below ground.

PMID- 18722646
TI  - Cadmium bioaccumulation factors for terrestrial species: application of the
      mechanistic bioaccumulation model OMEGA to explain field data.
AB  - In environmental risk assessment of metals it is often assumed that the biota-to
      soil accumulation factor (BSAF) is generic and constant. However, previous
      studies have shown that cadmium bioaccumulation factors of earthworms and small
      mammals are inversely related to total soil concentrations. Here, we provide an
      overview of cadmium accumulation in terrestrial species belonging to different
      trophic levels, including plants, snails and moles. Internal metal concentrations
      of these species are less than linearly related to total soil levels, which is in
      accordance with previously observed trends. The mechanistic bioaccumulation model
      OMEGA (Optimal Modeling for Ecotoxicological Applications) is used to provide a
      quantitative explanation of these trends in cadmium accumulation. Our results
      indicate that the model accurately predicts cadmium accumulation in earthworms,
      voles and shrews when accounting for geochemical availability of metals and
      saturable uptake kinetics.

PMID- 18722647
TI  - Using biochemical and isotope geochemistry to understand the environmental and
      public health implications of lead pollution in the lower Guadiana River, Iberia:
      a freshwater bivalve study.
AB  - Lead is a natural component of aquatic ecosystems with no known biological role
      and is highly toxic. Its toxicity stems from its ability to mimic biologically
      important metals and to produce membrane damage through lipid peroxidation (LPO).
      Most lead poisoning symptoms are thought to occur by interfering with an
      essential enzyme, delta-aminolevulinic acid dehydratase (ALAD), the activity of
      which is markedly inhibited by lead. The purpose of this work was to study the
      levels and effects of lead pollution (responses of ALAD and oxidative stress
      biomarker LPO) in the freshwater bivalve Corbicula fluminea along the lower
      Guadiana River (Portugal and Spain); a major river system impacted by historic
      mining pollution and more recent anthropogenic inputs. The results show that the
      enzymatic activity of ALAD is negatively correlated with the total Pb
      concentration of the whole tissue suggesting that ALAD has considerable potential
      as a biomarker of lead exposure in C. fluminea. To identify the sources of lead
      to which bivalves have been exposed, high precision (206)Pb/(204)Pb,
      (207)Pb/(204)Pb, (208)Pb/(204)/Pb ratios for C. fluminea confirm that historical
      mining activities in the Iberian Pyrite Belt are the dominant source of lead
      pollution in the lower Guadiana River. The isotope patterns however exhibit
      marked seasonal and geographic variation in response to rainfall and river water
      management. Locally, other anthropogenic sources of lead have been detected in C.
      fluminea close to population centres, thus adding to its versatility as a
      freshwater bio-indicator. Overall, the study highlights the value of natural
      ecosystems as monitors of water quality and their importance for public health
      assessment and surveillance.

PMID- 18722649
TI  - Asymptomatic hyperuricemia and serum uric acid concentration correlate with
      subclinical atherosclerosis in psoriatic arthritis patients without clinically
      evident cardiovascular disease.
AB  - OBJECTIVE: To establish whether serum uric acid concentration correlates with
      carotid intima-media wall thickness (IMT) in a cohort of psoriatic arthritis
      (PsA) patients without overt cardiovascular (CV) disease or classic CV risk
      factors who attended a community hospital. METHODS: A series of 52 PsA patients
      were assessed by carotid ultrasonography. Carotid IMT and carotid plaques were
      measured in the right common carotid artery. A correlation between serum uric
      acid concentration and carotid IMT was assessed and receiver operating
      characteristic curves to evaluate the ability of serum uric acid to predict
      carotid IMT > 0.90 mm and carotid plaques were performed. RESULTS: PsA patients
      with hyperuricemia (n = 6 [11.5%]) had greater carotid IMT (mean +/- standard
      deviation: 0.89 +/- 0.20 mm) than those without hyperuricemia (n = 46 [89%]; 0.67
      +/- 0.16 mm) (P = 0.01). Patients with carotid IMT < 0.60 mm had lower mean serum
      uric acid levels (4.7 +/- 1.2 mg/dL) than those with greater carotid IMT (5.3 +/-
      1.7 mg/dL for patients with carotid IMT 0.76-0.90 mm and 6.4 +/- 1.3 mg/dL for
      those with carotid IMT > 0.90 mm; P for trend = 0.02). A significant correlation
      between carotid IMT and serum uric acid concentration was observed (r = 0.337; P
      = 0.01). High serum uric acid levels were associated with an increased risk of
      having carotid IMT > 0.90 mm (Odds ratio = 2.66 [95% confidence interval: 1.08
      6.53], P = 0.03, area under receiver operating characteristic curve: 0.80) or
      with the presence of carotid plaques (Odds ratio = 1.85 [95%; confidence
      interval: 1.01-3.38], P = 0.05, area under receiver operating characteristic
      curve: 0.72). CONCLUSIONS: In PsA patients without clinically evident CV disease
      there is a correlation between serum uric acid concentration and subclinical
      atherosclerosis.

PMID- 18722650
TI  - Obesity is a significant risk factor for prostate cancer at the time of biopsy.
AB  - OBJECTIVES: Studies suggest obesity is associated with decreased prostate cancer
      risk. We hypothesized obesity is biologically associated with increased risk,
      although this is obscured owing to hemodilution of prostate-specific antigen
      (PSA) and larger prostate size. METHODS: We retrospectively studied 441
      consecutive men undergoing prostate biopsy between 1999 and 2003 at two equal
      access centers within the Veterans Affairs Greater Los Angeles Healthcare System.
      We estimated the association between obesity (body mass index >or= 30 kg/m(2))
      and positive biopsy and Gleason >or=4+3 using logistic regression analysis
      adjusting for multiple clinical characteristics. RESULTS: A total of 123 men
      (28%) were obese and 149 men (34%) had cancer. Median PSA and age were 5.7 ng/mL
      and 63.9 years, respectively. Obese men had significantly lower PSA
      concentrations (P = .02) and larger prostate volumes (P = .04). Obesity was not
      significantly related to age (P = .19) or race (P = .37). On univariate analysis,
      obesity was not associated with prostate cancer risk (odds ratio [OR] 1.13, 95%
      confidence interval [CI] 0.73-1.75, P = .58). However, after adjusting for
      multiple clinical characteristics, obesity was associated with significantly
      increased prostate cancer risk (OR 1.98, 95% CI 1.17-3.32, P = .01). After
      multivariable adjustment, there was no significant association between obesity
      and high-grade disease (P = .18). CONCLUSIONS: Without adjustment for clinical
      characteristics, obesity was not significantly associated with prostate cancer
      risk in this equal-access, clinic-based population. However, after adjusting for
      the lower PSA levels and the larger prostate size, obesity was associated with a
      98% increased prostate cancer risk. These findings support the fact that current
      prostate cancer screening practices may be biased against obese men.

PMID- 18722651
TI  - No effect of statins on biochemical outcomes after radiotherapy for localized
      prostate cancer.
AB  - OBJECTIVES: To examine the effect of concurrent statin use during definitive
      radiotherapy (RT) on the biochemical outcomes for localized prostate cancer.
      METHODS: A total of 968 patients treated with RT had information about medication
      use available. Of these, 23% had been taking using statins during RT. Progression
      free survival (PFS) was determined by a biochemical failure definition of
      prostate-specific antigen nadir plus 2 ng/mL, clinical failure, start of androgen
      deprivation therapy, or death. RESULTS: The mean patient age was 68 years. The
      median radiation dose was 76 Gy. Of the patients, 29% underwent androgen
      deprivation therapy. The 5-year overall survival rate was 83%. The median PFS
      time was 7.8 years versus 6.4 years, and the 5-year PFS rate was 70% versus 59%
      in favor of the statin users (P = 0.03). The analysis by risk group demonstrated
      no significant statin effect in any of the three risk strata. Stratification by
      hydrophilic versus hydrophobic statin agents revealed similar results.
      Multivariate analysis revealed that T stage (P <0.0001), pretreatment prostate
      specific antigen level (P <0.0001), and Gleason score (P = 0.0026) were
      significant predictors of PFS; however, statin use (P = 0.48), androgen
      deprivation therapy (P = 0.95), pelvic RT (P = 0.96), radiation dose (P = 0.13),
      age (P = 0.19), and year of treatment (P = 0.07) were not. CONCLUSIONS: Statin
      use did not affect PFS after adjusting for differences in treatment year and
      multiple prognostic factors. However, T stage, baseline prostate-specific antigen
      level, and Gleason score were critical determinants of prostate-specific antigen
      failure. These results did not differ when hydrophilic pravastatin was excluded.

PMID- 18722652
TI  - Bladder varices--rare cause of painless hematuria in idiopathic retroperitoneal
      fibrosis.
AB  - A patient presented to the urology outpatient department with complaints of
      recurrent episodes of painless hematuria. A contrast-enhanced computed tomography
      scan of the abdomen revealed vesical varices that had developed secondary to
      obstruction of the inferior vena cava. Additional investigation revealed
      idiopathic retroperitoneal fibrosis. Steroid therapy was started and tapered
      during a 6-week period. No recurrence of the hematuria was noted on follow-up. We
      have described a unique presentation of hematuria due to vesical varices in a
      patient with idiopathic retroperitoneal fibrosis.

PMID- 18722653
TI  - Adult Wilms tumor during gestational period.
AB  - We present a case of a 17-year-old pregnant girl, with hematuria. Magnetic
      resonance imaging showed a solid left renal mass. The patient had a radical
      nephrectomy during the 20th week gestation and the diagnosis was nephroblastoma.
      She gave birth to a healthy child at term and refused adjuvant treatment. She is
      disease-free after 24 months of follow-up. Based on the excellent results
      achieved while treating children with Wilms' tumor using surgery, chemotherapy
      and radiotherapy, adults with the same disease should be treated similarly. This
      treatment must be instituted early, even in pregnant women.

PMID- 18722654
TI  - Is injection therapy for stress urinary incontinence dead? Yes.

PMID- 18722655
TI  - Validation of treatment benefit scale for assessing subjective outcomes in
      treatment of overactive bladder.
AB  - OBJECTIVES: The assessment of patient-reported treatment benefits is a new
      efficacy outcome measure in overactive bladder (OAB) clinical trials. We
      conducted a retrospective psychometric validation of the Treatment Benefit Scale
      (TBS), a single-item scale used to assess the patient-reported benefits of
      treatment of OAB. METHODS: The data were collected in the context of 2 large
      Phase III, randomized, double-blind, placebo-controlled, clinical trials of an
      antimuscarinic treatment of patients with OAB. Psychometric validation was
      conducted by examining (a) scale variability, (b) construct validity, (c)
      divergent validity, (d) known-group validity, and (e) responsiveness of the TBS.
      RESULTS: The data from 1766 patients were evaluated. The TBS correlated
      significantly with the expected domains of the King's Health Questionnaire,
      International Consultation on Incontinence Questionnaire-Short Form, and other
      patient-reported assessments, providing evidence of construct validity. Divergent
      validity was supported by a lower correlation between the TBS and unrelated
      domains of the KHQ. Statistically significant differences in the TBS scores
      between patients who received active OAB treatment and those receiving placebo
      provided evidence of known-group validity. Scale responsiveness was demonstrated
      by effect sizes >0.8. CONCLUSIONS: The TBS demonstrated strong validity and
      responsiveness for the trial population data, both separately for each trial and
      pooled. This validation has demonstrated the psychometric properties of the TBS
      as a patient-reported clinical efficacy outcome measure and suggests that it
      could provide clinically relevant data for assessing the treatment response among
      patients in clinical trials of new therapies for OAB.

PMID- 18722657
TI  - Twenty-year review of radiotherapy for vaginal cancer: an institutional
      experience.
AB  - OBJECTIVE: To evaluate clinical outcome, prognostic factors and chronic morbidity
      with radiotherapy for vaginal cancer treatment. MATERIALS AND METHODS: 68
      patients with vaginal cancer treated by radical or adjuvant radiotherapy (RT)
      were selected. Five with rare subtypes of histopathology and 8 with
      adenocarcinoma were excluded from this study. 76.4% of the remainder had early
      stage diseases (stage I: 14, II: 28, III: 9, and IV: 4). The patients in the
      years from which they were treated were almost evenly distributed (1st 5 years:
      13, 2nd: 14, 3rd: 16, and 4th: 12). There were four treatment groups: external
      beam radiotherapy (EBRT) alone (n=18), brachytherapy (BT) alone (n=4), EBRT and
      BT (n=30), and surgery plus RT (n=3). RESULTS: Median follow-up was 50.3 months
      ranging from 3 to 213 months. 5-year overall survival (OS) was 55.6%, disease
      specific survival (DSS) was 77.3%, disease-free survival was 74.2%, and local
      control was 87.7%. Independent prognostic factors for DSS and OS were tumor
      stage, site and size (p<0.05). Late radiation toxicity was minimal in the bladder
      (4.6%) and bowel (4.6%). Vaginal morbidity was observed in 35 patients (63.6%).
      It was lowest in the BT alone (0%), and highest in the EBRT and BT group (82.1%),
      especially for those received more than 70 Gy (p=0.05, Odds ratio=4.64, 95%
      confidence interval: 1.01-21.65). CONCLUSION: This retrospective review suggested
      that tumor stage, site, and size were important prognostic factors in patients
      with vaginal cancer. Higher radiation dose was associated with more frequent
      vaginal toxicity.

PMID- 18722656
TI  - Artery-only occlusion may provide superior renal preservation during laparoscopic
      partial nephrectomy.
AB  - OBJECTIVES: Artery-only occlusion (AO) has been used during nephron-sparing
      surgery to reduce ischemic damage. However, this has not been demonstrated in
      laparoscopic partial nephrectomy (LPN). We compared our experience with AO and
      both artery and vein occlusion (AV) in LPN to optimize the method of ischemia.
      METHODS: This retrospective case-control study identified 25 patients who
      underwent AO during LPN and matched them to a cohort of 53 patients who underwent
      LPN with AV. The groups were compared for ischemia time, blood loss, transfusion
      rate, and renal function. RESULTS: The 2 cohorts were comparable on demographic
      data. Blood loss was similar, with AO and AV demonstrating equivalent transfusion
      rates. The 2 cohorts had similar warm ischemia times. Positive margin rate was
      not affected by venous backflow in the AO cohort (0% AO vs 1.9% AV, P = .679). No
      significant postoperative change in creatinine (Cr) or creatinine clearance
      (CrCl) was seen for AO; however, a significant change in Cr and CrCl was seen in
      AV. CONCLUSIONS: AO during LPN does not lead to a greater blood loss or an
      increased warm ischemia time. The benefit of AO on renal function is significant
      and requires further investigation.

PMID- 18722658
TI  - Angiotensin II type 1 receptor has impact on murine placentation.
AB  - Impaired placentation is a key step in the pathogenesis of important pregnancy
      disorders such as preeclampsia and fetal growth restriction. A role of
      angiotensin II in placental development can be assumed from the expression of
      angiotensin receptors on trophoblast from the earliest stages of pregnancy. To
      understand the role of angiotensin II type 1 (AT1) receptors in placental
      development, we investigated placentae of AT1a-deficient mice early in pregnancy
      (day 13 postconception). The number of alive newborns was significantly reduced
      in AT1a-deficient mice caused by placental malformations in 30% of all utero
      placental units. Importantly, no embryonic structure was observable within the
      uterine segments harboring the malformed placentae. Immunohistochemistry with an
      antibody against murine betahCG-equivalent stained homogeneously in almost all
      cells in the altered placentae indicating still an endocrine-active trophoblast.
      However, the typical structure of the murine wild-type placenta in
      spongiotrophoblast, giant cells, and labyrinth was abolished in malformed
      placental tissue deficient in the AT1a receptor. Recent epidemiological studies
      revealed the detrimental effect of an AT1 blockade for fetal outcome due to renal
      malformations and a reduced birth weight. For the latter, our findings provide an
      early mechanistic explanation. The lack in AT1 stimulation causes an impaired
      trophoblast maturation leading to impaired placental function.

PMID- 18722659
TI  - Metabolites of acute promyelocytic leukemia cells participate in contributing to
      hypertriglyceridemia induced by all-trans retinoic acid.

PMID- 18722660
TI  - Subacute toxicity of polychlorinated naphthalenes and their effect on cytochrome
      P-450.
AB  - The aim of the study was to investigate the subacute toxicity of a
      polychlorinated naphthalene (PCN) mixture and its effect on cytochrome P-450
      levels in rats. The animals were administered PCNs intragastrically in repeated
      daily doses of 1, 10, and 100 mg/kg. The animals were dissected after 7, 14, or
      21 doses. Doses of 10 and 100 mg/kg induced a significant decrease in the body
      weight at all time points of the experiment compared with the control group. The
      exposure to PCNs increased both the level of total cytochrome P-450 and the
      activity of CYP 1A at the same time points. In the groups of rats given PCNs in
      doses of 10 and 100 mg/kg, an evident dose- and time-dependent increase in
      malondialdehyde (MDA) level was observed throughout the experiment. The
      correlation between the increased MDA and decreased glutathione (GSH) levels in
      the liver was also observed.

PMID- 18722661
TI  - SO(2) inhalation induces protein oxidation, DNA-protein crosslinks and apoptosis
      in rat hippocampus.
AB  - Previous studies provide evidence for the possible neurotoxicity of SO(2), but
      little information is available about its mechanisms. In the present study, SO(2)
      inhalation-induced effects on the protein oxidation, DNA-protein crosslinks and
      apoptosis in rat hippocampus were studied, by exposing Wistar rats to SO(2) at
      14, 28 and 56mg/m(3). The results indicate that the protein carbonyl content, an
      indicator of protein oxidation, and DNA-protein crosslink coefficient were
      significantly augmented with concentration-dependent properties. In addition,
      SO(2) inhalation at all concentrations tested caused the increases of caspase-3
      activity and number of TUNEL positive staining neuron and the statistical
      difference was observed after 28 and 56mg/m(3) exposure, suggesting the
      occurrence of apoptosis. The results imply that attacking protein, nucleic acids
      and lipids by free radicals, generated via SO(2) derivatives in vivo, is one of
      the main mechanisms for SO(2)-induced injuries in central neuronal system.

PMID- 18722662
TI  - [Melanocytic cervical schwannoma].

PMID- 18722663
TI  - Coexistence of reversible cerebral neurotoxicity and irreversible cerebellar
      atrophy following an intrathecal methotrexate chemotherapy: two case reports.

PMID- 18722664
TI  - Low molecular weight dextran sulfate as complement inhibitor and cytoprotectant
      in solid organ and islet transplantation.
AB  - Complement is an essential part of the innate immune system and plays a crucial
      role in organ and islet transplantation. Its activation, triggered for example by
      ischemia/reperfusion (I/R), significantly influences graft survival, and blocking
      of complement by inhibitors has been shown to attenuate I/R injury. Another
      player of innate immunity are the dendritic cells (DC), which form an important
      link between innate and adaptive immunity. DC are relevant in the induction of an
      immune response as well as in the maintenance of tolerance. Modulation or
      inhibition of both components, complement and DC, may be crucial to improve the
      clinical outcome of solid organ as well as islet transplantation. Low molecular
      weight dextran sulfate (DXS), a well-known complement inhibitor, has been shown
      to prevent complement-mediated damage of the donor graft endothelium and is thus
      acting as an endothelial protectant. In this review we will discuss the evidence
      for this cytoprotective effect of DXS and also highlight recent data which show
      that DXS inhibits the maturation of human DC. Taken together the available data
      suggest that DXS may be a useful reagent to prevent the activation of innate
      immunity, both in solid organ and islet transplantation.

PMID- 18722665
TI  - Induction of TLR2 expression by inflammatory stimuli is required for endothelial
      cell responses to lipopeptides.
AB  - Human endothelial cells (EC) express Toll-like receptor 4 (TLR4), a receptor for
      lipopolysaccharides (LPS), but little or no TLR2, a lipopeptide receptor. The aim
      of this study was to investigate to what extent inflammatory stimuli modify the
      expression by EC of TLR4 and TLR2, of the TLR2 co-receptors TLR1 and TLR6 and of
      the TLR2-accessory proteins CD14 and CD36. Stimulation of umbilical vein derived
      EC with TNF-alpha, LPS or IL-1beta for 24h induced a strong increase in TLR2 mRNA
      but not in TLR1, TLR4 and TLR6 mRNA. Inflammatory activation had little effect on
      CD14 mRNA, but decreased the expression of CD36 mRNA. TLR2 antigen was readily
      detected by flow cytometry on activated EC, but not on resting EC. A significant
      proportion of TLR2 was found to be located intracellularly. By using specific
      signalling pathway inhibitors we established that the induction of TLR2 by
      inflammatory stimuli was dependent on NF-kappaB, p38-MAP kinase and c-Jun kinase.
      IRAK-1 phosphorylation after treatment with 10mug/ml of lipoteichoic acid (LTA),
      a TLR2 agonist, was only observed in TNF-alpha-stimulated EC and not in resting
      EC. Furthermore, LTA potentiated the increase of the inflammatory markers E
      Selectin or IL-8 in EC pre-treated with TNF-alpha, LPS or IL-1beta, but not in
      resting EC. These results imply that the up-regulated TLR2 is functionally
      active. Interestingly, LTA had no effect on TLR2 expression, nor maintained TLR2
      expression, in activated EC. This suggests that lipopeptide responses of EC are
      dependent on the continued presence of inflammatory cytokines, provided by other
      cell types, or LPS. In conclusion, inflammatory stimuli induce a high TLR2
      expression in EC, which in turn enables the cells to strongly respond to
      lipopeptides. The up-regulation of TLR2 may be of relevance for the vascular
      effects of Gram-positive bacteria.

PMID- 18722666
TI  - Drusen ultrastructure imaging with spectral domain optical coherence tomography
      in age-related macular degeneration.
AB  - PURPOSE: To categorize drusen ultrastructure in age-related macular degeneration
      (AMD) using spectral domain optical coherence tomography (SDOCT) and correlate
      the tomographic and photographic drusen appearances. DESIGN: Prospective case
      series. PARTICIPANTS: Thirty-one eyes of 31 patients with non-neovascular AMD.
      METHODS: Subjects with drusen and a clinical diagnosis of AMD were enrolled in an
      SDOCT imaging study from August of 2005 to May of 2007. Foveal linear scans were
      acquired, and the image data were processed for analysis. Drusen were scored by 4
      morphologic categories: shape, predominant internal reflectivity, homogeneity,
      and presence of overlying hyper-reflective foci. The prevalences of each
      morphologic pattern and combinations of morphologic patterns observed were
      calculated. The photographic appearance of each druse was compared with the
      tomographic classification. Interobserver and intraobserver agreement analysis
      was performed. MAIN OUTCOME MEASURES: Prevalence of morphologic parameters using
      SDOCT. RESULTS: Twenty-one eyes of 21 patients had SDOCT B-scans of adequate
      quality for analysis. On the basis of the above morphologic categories, 17
      different drusen patterns were found in 120 total drusen. The most common was
      convex, homogeneous, with medium internal reflectivity, and without overlying
      hyper-reflective foci, present in 17 of 21 eyes (81%). Of the 16 eyes (76%) with
      nonhomogeneous drusen, 5 had a distinct hyper-reflective core. Hyper-reflective
      foci overlying drusen were in 7 eyes (33%). Although half of the photographically
      soft-indistinct drusen were convex with medium internal reflectivity and
      homogeneous without overlying hyper-reflective foci, the other half had
      significant variability in their tomographic appearance. Both interobserver and
      intraobserver agreement in drusen grading were high. Readers agreed the most when
      grading drusen shape and reflectivity, whereas the least agreement was for drusen
      homogeneity. CONCLUSIONS: Drusen ultrastructure can be imaged with SDOCT and
      characterized with a simple grading system. Photographic appearance may predict
      some but not all tomographic appearances. Trained observers have a high level of
      agreement with this grading system. These in vivo morphologic characteristics
      imaged with SDOCT may be distinct subclasses of drusen types, may relate closely
      to ultrastructural drusen elements identified in cadaveric eyes, and may be
      useful imaging biomarkers for disease severity or risk of progression. This will
      require validation from further studies.

PMID- 18722667
TI  - A prospective study of binocular visual function before and after successful
      surgery to remove a unilateral epiretinal membrane.
AB  - OBJECTIVE: To examine the effect of a unilateral epiretinal membrane (uERM) on
      visual acuity, stereopsis, and motor fusion in patients before and after
      successful surgery to remove the membrane. DESIGN: Cohort study. PARTICIPANTS:
      Twenty-seven consecutive patients undergoing surgery to remove an idiopathic uERM
      and 30 normal control subjects. METHODS: Patients underwent full orthoptic
      examination before and between 3 and 6 months after surgery to remove a uERM.
      Stereoacuities were analyzed statistically using the Wilcoxon signed-rank test,
      Mann-Whitney U test, and Spearman correlation. Motor fusion ranges and visual
      acuities were compared using paired and unpaired t tests, with correlations
      examined by linear regression. MAIN OUTCOME MEASURES: Snellen visual acuity, TNO
      (stereoscopic acuity test of the Netherlands; Netherlands Organisation for
      Applied Scientific Research; Lameris Ootech BV, Nieuwegein, the Netherlands) and
      Titmus stereoacuity, motor fusion range. RESULTS: Postoperative acuity and
      improvement in visual acuity after removal of a uERM were better in patients with
      a shorter duration of symptoms. Stereoacuity was substantially reduced in the
      presence of a uERM (TNO, P<0.001; Titmus, P<0.001; Mann-Whitney U test), as were
      total motor fusion ranges at near and distance (near P = 0.002; distance P =
      0.015; t test). Stereoacuity was worse in patients with symptoms of longer
      duration (TNO, P = 0.21; Titmus, P = 0.045; Spearman rank correlation). After
      successful surgery, stereoscopic function improved. This improvement occurred
      mainly in those patients with better preoperative stereoacuity and a shorter
      duration of symptoms. CONCLUSIONS: Improvement in visual acuity after surgery was
      greater in patients with visual symptoms of shorter duration. A uERM adversely
      affected stereoscopic function, an effect that increased with time. The best
      monocular and binocular visual outcomes occurred in those patients who had
      earlier surgery.

PMID- 18722668
TI  - Spectral, electrochemical, and catalytic properties of a homologous series of
      manganese porphyrins as cytochrome P450 model: the effect of the degree of beta
      bromination.
AB  - A homologous series of beta-brominated porphyrins derived from meso-tetrakis(4
      carbomethoxyphenyl)porphyrinatomanganese(III) chloride, i.e.,
      Mn(III)(Br(x)TCMPP)Cl (x=0,2,4,6, and 8), was prepared and investigated as
      cytochrome P450 models. Hydroxylations of cyclohexane by iodosylbenzene (PhIO)
      and iodobenzene diacetate (PhI(OAc)(2)) in the presence or absence of water were
      carried out as P450 model reactions. The influence of the degree of beta
      bromination of the macrocycle on the UV-vis spectra, the Mn(III)/Mn(II) reduction
      potential, and the catalytic properties of the Mn(III)(Br(x)TCMPP)Cl (x=0,2,4,6,
      and 8) series were examined. The catalytic efficiency does not correlate with the
      Mn(III)/Mn(II) reduction potential and shows a bell-shaped behavior, where the
      best results are achieved with the hexabrominated complex. Better hydroxylation
      yields were achieved by using PhI(OAc)(2) as oxygen donor, but at expenses of
      catalyst recovery; addition of water to this system resulted in a increase in the
      reaction rate. Recycling of the more oxidatively robust complexes
      Mn(III)(Br(6)TCMPP)Cl and Mn(III)(Br(8)TCMPP)Cl is feasible when using PhIO as
      oxygen donor. Selectivity and UV-vis data suggested that hydroxylation by both
      PhIO and PhI(OAc)(2) share closely related active species and mechanism. We also
      show that the Mn(III)/Mn(II) reduction potentials are inappropriate predictors of
      P450-type activity of Mn porphyrin-catalyzed oxidations.

PMID- 18722669
TI  - A preliminary study to evaluate the effect of intravenous ribavirin treatment on
      survival rates in Crimean-Congo hemorrhagic fever.

PMID- 18722670
TI  - Bleuler revisited: psychomotor slowing in schizophrenia as part of a catatonic
      symptom cluster.
AB  - In schizophrenia, psychomotor slowing and stereotypy are poorly delineated from
      cognitive deficits like diminished processing speed. Inpatients' performance
      outcomes on a line-copying task, a task assessing stereotypy and a processing
      speed task are compared. Results suggested that psychomotor slowing and
      stereotypy are related and may represent a catatonic symptom cluster.

PMID- 18722671
TI  - Increased tumor necrosis factor-alpha concentrations with interleukin-4
      concentrations in exacerbations of schizophrenia.
AB  - Several studies have indicated that cytokines may be involved in the
      pathophysiology of schizophrenia. Previous studies, however, have yielded
      contradictory results; in this study we assess the plasma levels of both T-helper
      1 (Th1) and T-helper-2 (Th2) cytokines in patients with acute exacerbations of
      schizophrenia. Plasma concentrations of interleukin-4 (IL-4), interleukin-6 (IL
      6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-alpha
      (TNF-alpha) and soluble receptor of interleukin-6 (sIL-6R) were measured with
      high sensitivity, enzyme-linked immunosorbent assays (ELISA) in patients with
      acute exacerbations of schizophrenia as compared with healthy controls. Patients
      with an acute exacerbation of schizophrenia had significantly increased
      production of TNF-alpha and significantly reduced production of IL-4 as compared
      with healthy subjects. No significant difference was observed in IL-6, sIL-6R, IL
      8 and IL-10. Acute exacerbations of schizophrenia are associated with increased
      TNF-alpha concentrations (Th1) with concomitantly reduced concentrations of IL-4
      (Th2) and a resulting increased TNF-alpha/IL-4 ratio.

PMID- 18722672
TI  - Chitosan microspheres as candidate plasmid vaccine carrier for oral immunisation
      of Japanese flounder (Paralichthys olivaceus).
AB  - Oral DNA-based immunotherapy is a new treatment option for fish immunisation in
      intensive culture. However, because of the existence of the nucleases and severe
      gastrointestinal conditions, DNA-based vaccines can be hydrolyzed or denatured.
      In our laboratory, a plasmid DNA (pDNA) containing major capsid protein (MCP)
      gene of lymphocystis disease virus (LCDV) was prepared, and then pDNA was
      encapsulated in chitosan microspheres through an emulsion-based methodology. The
      yield, loading percent and encapsulation efficiency of microspheres were 93.6%,
      0.3% and 94.5%, respectively. Scanning electron microscopy (SEM) showed that pDNA
      loaded microspheres yielded a spherical shape with smooth surfaces. The
      disproportion of super-coiled to open circle and linear pDNA suggested that high
      transfection efficiencies of pDNA in microspheres were retained. The cumulative
      release of pDNA showed that chitosan microspheres were resistant to degradation
      in simulated gastrointestinal tract environment. The release profile at PBS
      buffer (pH 7.4) displayed that pDNA-loaded chitosan microspheres had a release up
      to 42 days after intestinal imbibition. RT-PCR showed that RNA containing
      information of MCP gene existed in various tissues 10-90 days post-vaccination.
      SDS-PAGE and immunofluorescent images indicated that pDNA expressed MCP in
      tissues of fish 10-90 days after oral administration. In addition, indirect ELISA
      displayed that the immune responses of sera were positive (O.D.> or =0.3) from
      week 1 to week 16 for fish vaccinated with microspheres, in comparison with fish
      vaccinated with naked pDNA. Data obtained suggested that chitosan microspheres
      were promising carriers for oral pDNA vaccine. Because this encapsulation
      technique was easy to operate and immunisation efficacy of microspheres loaded
      with pDNA was significant, it had potential to be used in drug delivery
      applications.

PMID- 18722673
TI  - Cellular and cytokine responses in feathers of chickens vaccinated against
      Marek's disease.
AB  - In Marek's disease virus infection, feather follicle epithelium (FFE) constitutes
      the site of formation of infectious virus particles and virus shedding. The
      objective of this study was to characterize cellular and cytokine responses as
      indicators of cell-mediated immune response in FFE and associated feather pulp
      following immunization against Marek's disease. Analysis of feather tips
      collected between 4 and 28 days post-immunization (d.p.i.) from chickens
      vaccinated post-hatch with either CVI988/Rispens or herpesvirus of turkeys
      revealed that replication of these vaccine viruses started at 7d.p.i., peaked by
      21d.p.i., and subsequently, showed a declining trend. This pattern of viral
      replication, which led to viral genome accumulation in feather tips, was
      associated with infiltration of T cell subsets particularly CD8+ T cells into the
      feather pulp area and the expression of cytokine genes such as interferon-gamma,
      which is an indication of elicitation of cell-mediated immune responses at the
      site of virus shedding.

PMID- 18722674
TI  - Molecular cloning and expression analysis of porcine gamma-interferon-inducible
      lysosomal thiol reductase (GILT).
AB  - A porcine interferon-gamma-inducible lysosomal thiol reductase (GILT) cDNA,
      designated pGILT, was cloned by RT-PCR and rapid amplification of cDNA ends
      (RACE) strategies. The full-length cDNA of pGILT consists of 1,062 bp with a 741
      bp open reading frame, encoding 246 amino acids, with a putative molecular weight
      of 29.5 kDa. The deduced pGILT possesses the typical structural feature of
      mammalian GILT, including an active-site CXXC motif, a GILT signature sequence
      CQHGX(2)ECX(2)NX(4)C, and 10 conserved cysteines. The genomic DNA sequence of
      pGILT contains seven exons and six introns, which is similar to vertebrate GILT
      exon-intron organization. The result of real-time PCR showed that GILT is
      expressed in many tissues in the pig, including spleen, liver, lung, heart,
      intestine, blood and kidney. And the pGILT expression is obviously up-regulated
      in spleen and blood after induction with LPS. These results suggesting that pGILT
      is highly likely to play a role in the innate immune responses in porcine. It
      also provided the basis for investigations on the role of GILT in this important
      domestic species and an animal model for human diseases.

PMID- 18722675
TI  - The myasthenia gravis thymus: a rare source of human autoantibody-secreting
      plasma cells for testing potential therapeutics.
AB  - In early-onset myasthenia gravis (EOMG), the thymus is colonized by lymph node
      like infiltrates including T cell areas and germinal centers. Our Group(1) showed
      (1978) spontaneous anti-acetylcholine receptor (AChR) autoantibody production by
      EOMG thymic cells. Especially after enzymic dispersal, these are enriched in
      plasma cells that are evidently autonomous, long-lived, terminally differentiated
      and radio-resistant. Radiolabeled AChR is highly sensitive both for localizing
      them in situ and detecting their ongoing antibody production in culture at
      limiting cell numbers. Thus EOMG thymi are a readily available source of specific
      autoimmune human plasma cells suitable for studying their biology and testing new
      therapies.

PMID- 18722676
TI  - Thymoma-associated myasthenia gravis: outcome, clinical and pathological
      correlations in 197 patients on a 20-year experience.
AB  - We studied 197 patients with thymoma-associated myasthenia gravis (T-MG) to
      identify variables that can influence the natural history of the disease and the
      therapeutical approaches. Multivariate analysis showed that neither clinical nor
      pathological variables were associated with a better chance to reach complete
      stable remission. The video-assisted thoracoscopic extended thymectomy (VATET)
      was not significantly correlated with a lower chance of achieving complete stable
      remission compared with the classical transsternal approach (T-3b) (p=0.1090).
      Thymoma recurrence was not correlated with surgery by VATET or T-3b. VATET was
      safe and reliable for removal of thymoma. The low chance of achieving remission
      (9.64%) in T-MG underlines the importance of an early diagnosis as well as the
      need for more aggressive therapeutic strategies.

PMID- 18722677
TI  - 27-Hydroxycholesterol: a potential endogenous regulator of estrogen receptor
      signaling.
AB  - The selective estrogen receptor modulators (SERMs) are synthetic pharmaceuticals,
      the relative agonist and antagonist activities of which are not equivalent in all
      cells. Their discovery has raised the possibility that endogenous small molecules
      might exist that have similar properties and could have important physiological
      roles. In support of this hypothesis is the recent demonstration that the
      oxysterol 27-hydroxycholesterol (27HC) interacts with and modulates the
      transcriptional activity of both estrogen receptor (ER) subtypes and that the
      relative agonist and antagonist activity of 27HC is influenced by both cell and
      promoter context. Although there is limited information available on the role of
      27HC in classical estrogen-responsive tissues, that which is available in animal
      models of cardiovascular disease and cellular models of breast cancer support a
      role for this ligand in ER signaling. These results provide an interesting
      potential link between cholesterol (and cholesterol metabolism) and ER function,
      the physiological and pathological importance of which remains to be determined.

PMID- 18722679
TI  - The use of laser angioplasty in patients with acute myocardial infarction: a new
      era.

PMID- 18722678
TI  - Aetiology and risk factors of peripartum cardiomyopathy: a systematic review.
AB  - BACKGROUND: Peripartum cardiomyopathy (PPCM) is a disorder of unknown aetiology
      in which heart failure due to left ventricular dysfunction occurs between the
      last month of pregnancy and first five months post-partum. Theories abound
      concerning the specific cause and risk factors for PPCM, but none have been
      accepted universally. The primary objective of this review was to summarize the
      state of knowledge on the pathogenesis of PPCM, especially in light of recent
      studies. METHODS: We searched MEDLINE (January 1966-September 2007), OVID, and
      reference lists of articles for studies containing information on the aetiology
      and risk factors for PPCM, and published in English. RESULTS: The literature
      reveals a wealth of articles proposing various mechanisms for aetiology and risk
      factors of PPCM. There is conflicting evidence on the pathogenetic role of viral
      myocarditis, abnormal immune response to pregnancy, abnormal response to the
      haemodynamic stress of pregnancy, accelerated myocyte apoptosis, cytokine-induced
      inflammation, malnutrition, genetic factors, excessive prolactin production,
      abnormal hormonal function, increased adrenergic tone, and myocardial ischaemia.
      A number of factors are postulated to increase the risk of the development of
      PPCM. These include non-Caucasian ethnicity, advanced maternal age, multiparity,
      poor socioeconomic status, multiple pregnancy and prolonged tocolytic use. The
      authors call for a strict definition of PPCM that excludes known causes of heart
      failure, such as the pregnancy-induced hypertensive spectrum of disorders.
      CONCLUSION: The aetiology and risk factors for PPCM are poorly defined. There is
      a need for large-scale multi-centre epidemiological studies and registries to
      delineate the aetiology and pathogenesis of PPCM.

PMID- 18722680
TI  - Coronary myocardial bridge constitutes a risk: But how to manage it?
AB  - Myocardial bridges may cause angina pectoris, myocardial infarction, life
      threatening arrhythmias and even sudden cardiac death but most of them are
      harmless. Although the exact management is not well known, beta blockers seem to
      be the first choice. Stenting is controversial and one must think "twice" before
      stenting the bridged coronary artery.

PMID- 18722681
TI  - Effects of atorvastatin 80 mg daily on indices of matrix remodelling in 'high
      risk' patients with ischemic heart disease.
AB  - Recent evidence suggests that higher doses of statins could improve clinical
      outcomes compared to conventional doses, but whether this benefit is due to
      "additional" pleiotropic effects is uncertain. We tested the hypothesis that
      atorvastatin 80 mg/day would have beneficial effects on indices of matrix
      remodelling (matrix metalloproteinase-1, MMP-1, and its tissue inhibitor, TIMP-1)
      in high-risk cardiovascular disease. We studied 27 "high-risk" patients
      (inclusion criteria: severe triple vessel but rejected for by-pass for extensive
      coronary disease, severe effort angina after coronary artery by-pass and
      premature coronary disease with > or =3 risk factors) with an abnormal lipid
      profile despite atorvastatin 40 mg/day, at baseline and at 3 months after
      increasing the statin dose to 80 mg/day. Baseline results in patients were
      compared to 22 healthy controls. At baseline, patients had lower levels of MMP-1
      compared to controls. When atorvastatin was increased to 80 mg/day, significant
      reduction in LDL-cholesterol was observed, whereas MMP-1 and TIMP-1 levels were
      increased. These, despite of atorvastatin 40 mg daily, 'high-risk' patients still
      demonstrated abnormal extracellular remodelling indices. Doubling the dose of
      atorvastatin resulted in significant improvement in extracellular remodelling
      indices.

PMID- 18722682
TI  - Does a targeting ligand influence nanoparticle tumor localization or uptake?
AB  - Inclusion of a tumor-targeting molecule in nanosized delivery systems increases
      their in vivo efficacy. However, the biodistribution and pharmacokinetics of the
      uptake of such particles have not yet been well addressed. Several recent papers
      have suggested that tumor-targeting ligands function primarily to increase
      intracellular uptake of the nanocomplex and do not influence tumor localization.
      However, other reports indicate that they do play a role in the accumulation in
      the tumor. One difference might be the presence or absence of poly-[ethylene
      glycol] (PEG) in the complex and its impact on the enhanced permeability and
      retention (EPR) effect. Further studies are clearly needed to more fully
      elucidate the influence of composition on tumor-targeted, systemic delivery of
      nanoparticles.

PMID- 18722683
TI  - Single-molecule DNA sequencing technologies for future genomics research.
AB  - During the current genomics revolution, the genomes of a large number of living
      organisms have been fully sequenced. However, with the advent of new sequencing
      technologies, genomics research is now at the threshold of a second revolution.
      Several second-generation sequencing platforms became available in 2007, but a
      further revolution in DNA resequencing technologies is being witnessed in 2008,
      with the launch of the first single-molecule DNA sequencer (Helicos Biosciences),
      which has already been used to resequence the genome of the M13 virus. This
      review discusses several single-molecule sequencing technologies that are
      expected to become available during the next few years and explains how they
      might impact on genomics research.

PMID- 18722684
TI  - Dose-individualized stereotactic body radiotherapy for T1-3N0 non-small cell lung
      cancer: long-term results and efficacy of adjuvant chemotherapy.
AB  - PURPOSE: To evaluate the efficacy of dose-individualized stereotactic body
      radiotherapy (SBRT) and adjuvant chemotherapy in stage T1-3N0M0 non-small cell
      lung cancer (NSCLC). MATERIALS AND METHODS: Sixty-five patients with T1-3N0M0
      NSCLC treated by SBRT between April 2001 and August 2005 were included. Twenty
      patients were CT-staged at stage T1, 34 at stage T2, and 11 at stage T3. All
      patients underwent no elective nodal irradiation. SBRT total doses ranged from
      71.8 to 115.2Gy of biological equivalent dose (BED) in 3.6 to 8.0Gy daily
      fractions. Seventeen patients were offered cisplatin-containing adjuvant
      chemotherapy. RESULTS: The overall response rate was 90.6% at six months. The 3-
      and 5-year overall survival rates for all patients were 57.3% and 35.1%,
      respectively, and for stage T1-2 patients these were 60.2, 36.5%, respectively.
      Of all patients, the 3- and 5-year overall survival rates of adjuvant
      chemotherapy group were 80.5% and 46.0%, respectively, and those of patients with
      SBRT alone were 49.6% and 31.5%, respectively. Patients who accepted adjuvant
      chemotherapy had a lower relapse rate and better overall survival. Acute
      toxicities were mild, and no long-term toxicity was observed. CONCLUSIONS:
      Patients treated with the dose-individualization strategy of SBRT showed
      excellent local control and improved survival. Adjuvant chemotherapy may reduce
      the frequency of relapse and increase overall survival in stage at T1-3N0M0 NSCLC
      patients.

PMID- 18722685
TI  - Plasma FGF-21 levels in type 2 diabetic patients with ketosis.
AB  - FGF-21 has been recently characterized as a potent metabolic regulator, but its
      pathophysiologic role in human remains unknown. In this study we investigate
      whether plasma FGF-21 level is different in patients with new-onset type 2
      diabetes mellitus (T2DM) and diabetic ketosis (T2DK). Sixty-eight patients with
      T2DM, 41 subjects with T2DK, and 52 sex- and age-matched normal controls
      participated in the study. Plasma FGF-21 levels were measured with a
      radioimmunoassay. The relationship between plasma FGF-21 levels and
      anthropometric and metabolic parameters was also analyzed. Plasma FGF-21 levels
      were higher in patients with T2DK and T2DM than in controls (4.05+/-0.18microg/L
      and 2.82+/-0.14microg/L vs. 2.28+/-0.16microg/L, P<0.01 and P<0.05,
      respectively). Fasting plasma FGF-21 was found to correlate positively and
      significantly with SBP, DBP, FBG, 2hPBG, HbA(1)c, HDL-C and FFA, but negatively
      with fasting plasma insulin, 2hIns and HOMA(IS). Multiple regression analysis
      showed that DBP, WHR, 2hIns, 2hPBG and FFA were independent to the factors
      influencing plasma FGF-21 levels. Increasing concentrations of FGF-21 were
      independently and significantly associated with T2DM and T2DK. The present work
      suggests that FGF-21 may play a role in the pathogenesis of T2DM and T2DK.

PMID- 18722686
TI  - Mucinous adenocarcinoma of the thymus: a distinct variant of thymic carcinoma.
AB  - BACKGROUND: Primary thymic mucinous adenocarcinoma is a recently described
      subtype of thymic carcinoma, which behaves aggressively. METHODS: The authors
      analyzed the clinical and pathological findings of three cases of thymic mucinous
      adenocarcinoma, and reviewed five cases previously reported in the English
      literature. RESULTS: The patients were two males and one female between the ages
      of 38 and 55 years. Macroscopically, the tumors were mostly solid and white to
      yellowish-white. Areas with a gelatinous appearance were present. Histologically,
      all of the tumors were adenocarcinomas with abundant mucin production, which
      resembled the mucinous adenocarcinomas of other organs. Malignant tumor cells in
      nests, tubules and cribriform structures floated in pools of extracellular mucin.
      In one case, associated thymic cysts were found at the periphery of the tumor.
      The cyst wall was partially lined by malignant mucinous epithelium, which showed
      transition from benign thymic epithelium. Immunohistochemically, all of the
      tumors showed positive immunoreactivity for cytokeratin (CK) 20 and
      carcinoembryonic antigen (CEA). CD5 was diffusely positive in one case, and
      focally positive in the other two cases. The prognoses of these cases were
      extremely poor, and two of the patients died within 24 months. CONCLUSION:
      Growing evidence suggests that mucinous adenocarcinoma is a distinct
      morphological variant of primary thymic carcinoma. We believe that clinicians and
      surgical pathologists should include thymic mucinous adenocarcinoma in the
      differential diagnosis of mediastinal adenocarcinoma.

PMID- 18722687
TI  - Coral reef management and conservation in light of rapidly evolving ecological
      paradigms.
AB  - The decline of many coral reef ecosystems in recent decades surprised experienced
      managers and researchers. It shattered old paradigms that these diverse
      ecosystems are spatially uniform and temporally stable on the scale of millennia.
      We now see reefs as heterogeneous, fragile, globally stressed ecosystems
      structured by strong positive or negative feedback processes. We review the
      causes and consequences of reef decline and ask whether management practices are
      addressing the problem at appropriate scales. We conclude that both science and
      management are currently failing to address the comanagement of extractive
      activities and ecological processes that drive ecosystems (e.g. productivity and
      herbivory). Most reef conservation efforts are directed toward reserve
      implementation, but new approaches are needed to sustain ecosystem function in
      exploited areas.

PMID- 18722688
TI  - Evolutionary implications of non-neutral mitochondrial genetic variation.
AB  - Sequence variation in mitochondrial DNA (mtDNA) was traditionally considered to
      be selectively neutral. However, an accumulating body of evidence indicates that
      this assumption is invalid. Furthermore, recent advances indicate that mtDNA
      polymorphism can be maintained within populations via selection on the joint
      mitochondrial-nuclear genotype. Here, we review the latest findings that show
      mitochondrial and cytoplasmic genetic variation for life-history traits and
      fitness. We highlight the key importance of the mitochondrial-nuclear interaction
      as a unit of selection and discuss the consequences of mitochondrially encoded
      fitness effects on several key evolutionary processes. Our goal is to draw
      attention to the profound, yet neglected, influence of the mitochondrial genome
      on the fields of ecology and evolution.

PMID- 18722689
TI  - Phylogeographic insights into cryptic glacial refugia.
AB  - The glacial episodes of the Quaternary (2.6 million years ago-present) were a
      major factor in shaping the present-day distributions of extant flora and fauna,
      with expansions and contractions of the ice sheets rendering large areas
      uninhabitable for most species. Fossil records suggest that many species survived
      glacial maxima by retreating to refugia, usually at lower latitudes. Recently,
      phylogeographic studies have given support to the existence of previously
      unknown, or cryptic, refugia. Here we summarise many of these insights into the
      glacial histories of species in cryptic refugia gained through phylogeographic
      approaches. Understanding such refugia might be important as the Earth heads into
      another period of climate change, in terms of predicting the effects on species
      distribution and survival.

PMID- 18722690
TI  - The accuracy of an out-of-hospital 12-lead ECG for the detection of ST-elevation
      myocardial infarction immediately after resuscitation.
AB  - STUDY OBJECTIVE: Severe myocardial ischemia is the leading cause of arrhythmic
      sudden cardiac death. It is unclear, however, in which percentage of patients
      sudden cardiac death is triggered by ST-elevation myocardial infarction (STEMI)
      and whether the diagnosis of STEMI can be reliably established immediately after
      resuscitation from out-of-hospital sudden cardiac death. METHODS: A 12-lead ECG
      was registered after return of spontaneous circulation after cardiac arrest.
      After hospital admission, further ECG, creatine kinase MB, and troponin measures;
      results of coronary angiograms; and autopsies were evaluated to confirm the
      definitive diagnosis of STEMI. RESULTS: Seventy-seven patients were included in
      our study (67% men, age 64 [14 to 93] years). STEMI was diagnosed in 44 patients.
      The diagnosis of myocardial infarction was confirmed in 84% of the 77 patients
      who survived to hospital admission. The sensitivity of the out-of-hospital ECG
      was 88% (95% confidence interval [CI] 74% to 96%), the specificity 69% (95% CI
      51% to 83%), the positive predictive value 77% (95% CI 62% to 87%), and the
      negative predictive value 83% (95% CI 64% to 87%). The accuracy of the out-of
      hospital ECG and that registered on admission was the same. CONCLUSION: The
      diagnosis of STEMI can be established in the field immediately after return of
      spontaneous circulation in most patients. This may enable an early decision about
      reperfusion therapy, ie, immediate out-of-hospital thrombolysis or targeted
      transfer for percutaneous coronary intervention.

PMID- 18722691
TI  - Forcing functions: the need for restraint.

PMID- 18722692
TI  - Beyond "communication failure".

PMID- 18722693
TI  - Hazards with medical devices: the role of design.

PMID- 18722694
TI  - Assessing clinical reasoning in pediatric emergency medicine: validity evidence
      for a Script Concordance Test.
AB  - STUDY OBJECTIVE: Clinical reasoning is a crucial skill for all residents to
      acquire during their training. During most patient encounters in pediatric
      emergency medicine, physicians and trainees are challenged by diagnostic,
      investigative, and treatment uncertainties. The Script Concordance Test may
      provide a means to assess reasoning skills in the context of uncertainty in the
      practice of pediatric emergency medicine. We gathered validity evidence for the
      use of a pediatric emergency medicine Script Concordance Test to evaluate
      residents' reasoning skills. METHODS: A 1-hour test containing 60 questions
      nested in 38 cases was administered to 53 residents at the end of their pediatric
      emergency medicine rotation at 1 academic institution. Twelve experienced
      pediatricians were part of a reference panel to establish the basis for the
      scoring process. RESULTS: An optimized version of the test, based on positive
      item discrimination data, contained 30 cases and 50 questions. Scores ranged from
      48% to 82%, with a mean score of 69.9 (SD=11.5). The reliability of the optimized
      test (Cronbach's alpha) was 0.77. Performance on the test increased as the level
      of experience of the residents increased. The residents considered the Script
      Concordance Test true to real-life clinical problems and had enough time to
      complete the test. CONCLUSION: This pediatric emergency medicine Script
      Concordance Test was reliable and useful to assess the progression of clinical
      reasoning during residency training.

PMID- 18722695
TI  - [New therapies for type 2 diabetes: what place for incretin-based agents and
      rimonabant compared to the previous ones?].
AB  - Treatment of type 2 diabetes (T2DM) is based on lifestyle changes and oral
      antidiabetic agents or insulin. The UKPDS study has confirmed metformin (Met) as
      the initial monotherapy. Accordingly, Met is widely regarded as the first drug of
      choice for most patients with T2DM. Safety and efficacy of sulphonylureas (SU)
      have been confirmed by several clinical trials. Recently, thiazolidinediones
      (TZD) have addressed some aspects of insulin-resistance that characterized
      several T2DM patients. However, SU and TZD are associated with various side
      effects that limit their use in many patients. New agents have been recently
      developed which potentiate the activity of the incretin (GLP1). GLP1, a gut
      hormone secreted in response to meal ingestion, is rapidly degraded by
      dipeptidylpeptidase-4 (DPP-4). GLP1 enhances insulin secretion and inhibits
      glucagon secretion in a glucose-dependent manner, delays gastric emptying and, in
      animal studies, preserves beta-cell mass by reducing apoptosis and stimulates of
      beta-cell proliferation. GLP1 levels are abnormally low in T2DM patients. Two
      classes of agents based on GLP1 have been launched: DPP-4 inhibitors and DPP-4
      resistant GLP1 analogues. Randomized studies confirmed their efficacy to improve
      glycemic control in T2DM patients. Orally administered DPP-4 inhibitors reduce
      HbA1c by 0.5-1.1%, without hypoglycaemic events and no weight gain. The sub
      cutaneous injected GLP1 analogues (exenatide and liraglutide) show larger
      reductions in HbA1c by 0.8-1.7% and weight loss but are associated with
      gastrointestinal side effects contributing to a significant treatment
      interruption. Several studies support the use of DPP-4 inhibitors in combination
      with Met as a promising second line treatment.

PMID- 18722696
TI  - [Whipple's disease].
AB  - Whipple's disease is a chronic, multisystemic, curable, bacterial infection that
      usually affects middle-aged men. It has a wide range of clinical manifestations.
      In the historical presentation, weight loss and diarrhoea are the most common
      symptoms and are preceded in three-quarters of cases by arthritis for a mean of
      six years. Long-term, unexplained, seronegative oligoarthritis or polyarthritis
      of large joints with a palindromic or relapsing course is typical. In most
      patients, periodic acid-Schiff staining of proximal small bowel biopsy specimens
      reveals inclusions within the macrophages, corresponding to bacterial structures.
      However, patients may have no gastrointestinal symptoms, negative jejunum biopsy
      results and even negative PCR tests. Even in the absence of gastrointestinal
      symptoms, Whipple's disease should be considered in case of negative blood
      culture endocarditis, unexplained central neurological manifestations or
      unexplained arthritis. Identification of the causative bacterium, Tropheryma
      whipplei, has led to the development of PCR as a diagnostic tool, particularly
      useful in patients in the early stages of the disease or with atypical disease.
      The recent cultivation of T. whipplei and the complete sequencing of its genome
      should improve our understanding and treatment of the disease. The future
      development of an assay for detection of specific antibodies in the serum and
      generalization of the immunohistochemical detection of antigenic bacterial
      structures may allow earlier diagnosis, thereby preventing the development of the
      severe late systemic and sometimes fatal forms of the disease.

PMID- 18722697
TI  - Cardiovascular disease and heritability of the prothrombotic state.
AB  - Atherothrombotic disease remains a major cause of mortality worldwide, and family
      clustering suggests an important contribution of genetic factors to disease
      pathogenesis. Thrombus formation represents the final step in atherothrombosis, a
      process influenced by genetic and environmental factors. A major difficulty of
      investigating the genetic regulation of thrombotic conditions is the complexity
      of the phenotype and the relatively modest effects of individual genetic
      variations. We address in this review genetic aspects involved in regulating
      thrombosis potential and their impact on the development of atherothrombotic
      disease. The effects of common genetic polymorphisms in clotting factors are
      discussed and examples of complex gene-gene and gene-environment interactions are
      highlighted. Understanding the effects of genetic factors on predisposition to
      thrombotic disease and unravelling the complex gene-environment interactions will
      help to better understand the pathophysiology of this complex condition, which
      will enable the development of new preventative and treatment strategies.

PMID- 18722698
TI  - Effect of cationic and anionic surfactants on the sorption and desorption of
      perfluorooctane sulfonate (PFOS) on natural sediments.
AB  - Sorption and desorption of PFOS at water-sediment interfaces were investigated in
      the presence of a cationic surfactant, cetyltrimethylammonium bromide (CTAB), and
      an anionic surfactant, sodium dodecylbenzene sulfonate (SDBS). CTAB remarkably
      enhanced the sorption of PFOS on the sediment. In contrast, the influence of SDBS
      to the sorption of PFOS was concentration dependent. Two contrasting factors were
      responsible for the phenomenon. One was the sorption of the surfactant itself to
      the sediment, which enhanced the sorption of PFOS. The other was the increase in
      solubility of PFOS caused by the adding of surfactants, which decreased the
      sorption of PFOS. SDBS had a much lower sorption capacity, but rather strong
      ability to increase the solubility of PFOS. High levels of SDBS remarkably
      reduced the sorption of PFOS on the sediment. These results imply that cationic
      and anionic surfactants may have contrast impacts on the distribution and
      transport of PFOS in the environment.

PMID- 18722700
TI  - The female advantage in object location memory is robust to verbalizability and
      mode of presentation of test stimuli.
AB  - This study extends Duff and Hampson's [Duff, S., & Hampson, E. (2001). A sex
      difference on a novel spatial working memory task in humans. Brain and
      Cognition,47, 470-493] finding of a sex-related difference in favor of females
      for an object location memory task. Twenty female and 20 male undergraduate
      students performed both manual and computer-generated versions of the task using
      stimuli that varied in degree of verbalizability. A 2x2x3 ANOVA with Sex as a
      between-subjects factor, and Presentation (manual or computer) and Stimuli
      (common objects, common shapes, and novel shapes) as within-subjects repeated
      measures revealed a significant main effect for Sex. Females made fewer errors
      than males regardless of presentation and across the three levels of
      verbalizability (i.e., stimulus types); moreover, the effect size was considered
      "large" [Cohen, J. (1988). Statistical power analysis for the behavioral sciences
      (2nd ed.). Berlin: Springer]. These findings are interpreted within the context
      of the current literature that demonstrates a female advantage for object
      location memory (e.g., [Voyer, D., Postma, A., Brake, B., & Imperato-McGinley, J.
      (2007). Gender differences in object location memory: A meta-analysis.
      Psychonomic Bulletin and Review, 14, 23-38]).

PMID- 18722701
TI  - Urbanization and the likelihood of a cesarean section.
AB  - OBJECTIVE: This study examines the association between the likelihood of cesarean
      section (CS) and the degree of urbanization in Taiwan, exploring possible
      explanations for the difference. STUDY DESIGN: The database used in this study
      was the Taiwan 2004 National Health Insurance Research Database. A total of
      200,207 singleton deliveries fulfilled our criteria and were included in our
      study. The urbanization level of cities/towns where parturients resided at the
      time of delivery was stratified into seven categories. A multilevel logistic
      regression model was applied to examine the relative likelihood of CS by
      urbanization level after adjusting for parturient, physician and hospital
      characteristics. RESULTS: There was an upward trend in the CS rate with advancing
      urbanization level; the CS rates for urbanization level 1 (most urbanized)
      through 7 (least urbanized) were 33.7, 32.3, 30.4, 30.2 29.7, 29.5, and 28.6%,
      respectively. Compared with participants living at the highest urbanization
      level, the adjusted odds of a CS were 0.91 (95% CI=0.85-0.98, p=0.014), 0.84 (95%
      CI=0.78-0.91, p<0.001), 0.83 (95% CI=0.68-0.88, p<0.001), 0.79 (95% CI=0.72-0.86,
      p<0.001), and 0.70 (95% CI=0.62-0.80, p<0.001) times, respectively, for those
      living in cities/towns ranked from the third highest to the lowest levels of
      urbanization. CONCLUSIONS: We conclude that higher urbanization levels were
      associated with higher odds of CS. Highly urbanized communities could therefore
      be targeted for policy intervention aimed at reducing the unnecessary CS rate.

PMID- 18722702
TI  - Editorial comment on: laparoscopic retroperitoneal lymph node dissection: does it
      still have a role in the management of clinical stage I nonseminomatous testis
      cancer? A European perspective.

PMID- 18722703
TI  - Editorial comment on: laparoscopic retroperitoneal lymph node dissection: does it
      still have a role in the management of clinical stage I nonseminomatous testis
      cancer? A European perspective.

PMID- 18722704
TI  - Laparoscopic retroperitoneal lymph node dissection: does it still have a role in
      the management of clinical stage I nonseminomatous testis cancer? A European
      perspective.
AB  - CONTEXT: Laparoscopic retroperitoneal lymph node dissection (L-RPLND) is not
      recommended as standard tool in European Association of Urology (EAU) guidelines.
      OBJECTIVE: To update the role of L-RPLND in patients with clinical stage I
      nonseminomatous germ cell tumour (NSGCT) compared to open retroperitoneal lymph
      node dissection (O-RPLND). EVIDENCE ACQUISITION: A systematic literature search
      from 1992 to 2008 was performed in Medline, EMBASE, and Cochrane. The largest
      series from each group was considered. Comparative analysis was based on raw data
      of series published in 2000 and later. EVIDENCE SYNTHESIS: Results of >800
      patients treated by L-RPLND reported in 34 articles were analyzed. Lymph node
      dissection (LND) was based on modified templates, removing an average of 16 (5
      36) lymph nodes. At experienced centres, complication rates were 15.6% (9.4
      25.7), including 2% (0-5) retrograde ejaculation and 1.7% (0-6) reintervention.
      Operating room times are longer compared to O-RPLND (204 vs 186min). Five
      publications with a follow-up of 63 (36-89) mo include 557 patients. One hundred
      twenty-six of 140 (90%) patients with positive nodes (25%, range: 17-38) received
      adjuvant chemotherapy, resulting in a local relapse rate of 1.4% (0.7-2.3) with
      no in-field recurrence; rate of distant relapses was 3.3% (1.8-4.6), including
      one port-site metastasis; and rate of biochemical failure was 0.9% (0.7-2.3). Two
      of 14 patients with positive nodes (pN1) who did not receive adjuvant
      chemotherapy relapsed, both 8 mo after surgery, and were salvaged by
      chemotherapy. Compared with O-RPLND, there was no difference in relapse rates,
      percentage of patients receiving chemotherapy (29% vs 31%), chemotherapy (CTx)
      cycles per cohort (0.6), rate of salvage surgery (1.2% vs 1.5%), and patients
      with no evidence of disease (NED; 100% vs 99.7%). CONCLUSIONS: L-RPLND offers
      similar staging accuracy and long-term outcome to O-RPLND. In a late series of
      experienced L-RPLND centres, there was a trend towards fewer complications. L
      RPLND represents a valuable tool for experienced laparoscopic surgeons. Further
      studies must focus on the curative potential of the procedure in pathologic stage
      IIA.

PMID- 18722705
TI  - Editorial comment on: laparoscopic retroperitoneal lymph node dissection: does it
      still have a role in the management of clinical stage I nonseminomatous testis
      cancer? A European perspective.

PMID- 18722706
TI  - Editorial comment on: laparoscopic retroperitoneal lymph node dissection: does it
      still have a role in the management of clinical stage I nonseminomatous testis
      cancer? A European perspective.

PMID- 18722707
TI  - Sensor-based neuronavigation: evaluation of a large continuous patient
      population.
AB  - OBJECTIVE: Navigation systems enable neurosurgeons to guide operations with
      imaging data. Sensor-based neuronavigation uses an electromagnetic field and
      sensors to measure the positions of the patient's brain anatomy and the surgical
      instruments. The aim of this investigation was to determine the accuracy level of
      sensor-based tracking in a large patient collection. METHODS: This study covers
      250 patients operated upon during a continuous 5.5-year period. The patients had
      a wide range of indications and surgical procedures. The operations were
      performed with a direct current (DC) pulsed sensor-based electromagnetic
      navigation system. Four kinds of errors were measured: the fiducial registration
      error (FRE), the target registration error (TRE), brain shift, and the position
      error (PE). These errors were calculated for five subgroups of indications:
      target determination and trajectory guidance, functional navigation, skull base
      and neurocranium, determination of resection volume, and transnasal and
      transsphenoidal access. RESULTS: The overall mean FRE was 1.66mm (+/-0.61mm). The
      overall mean TREs were 1.33mm (+/-0.51mm) centroid and 1.59mm (+/-0.57mm)
      lesional. The overall mean brain shift for applicable cases was 1.61mm (+/
      1.14mm). The overall mean PE was 0.92mm (+/-0.54mm). CONCLUSIONS: By and large,
      modern sensor-based neuronavigation operates within an acceptable and commonplace
      degree of error. However, the neurosurgeon must remain critical in cases of small
      lesions, and must exert caution not to introduce further interference from metal
      objects or electromagnetic devices.

PMID- 18722709
TI  - Effective stimulation of growth in MCF-7 human breast cancer cells by inhibition
      of syntaxin18 by external guide sequence and ribonuclease P.
AB  - Syntaxin18 (Stx18) is an endoplasmic reticulum (ER)-membrane bound SNARE protein
      involved in membrane trafficking between the ER and Golgi as well as in
      phagocytosis. Stx18 has also been shown to physically interact with proteins
      involved in the cell cycle and apoptosis. These findings suggest the possible
      role of Stx18 in regulating cell growth. In this study, we used theoretically
      designed external guide sequence molecule which utilizes RNase P to cleave Stx18
      mRNA and down-regulate Stx18 levels in MCF-7 human breast cancer cells. We showed
      that down-regulation of Stx18 leads to significant enhancement of growth in MCF-7
      cells. Consistent with this finding was the observation that over-expression of
      Stx18 using the CMV promoter led to suppression of cell growth. Over-expressing
      Stx18 had no effect on c-myc mRNA expression and half-life, suggesting that the
      mechanism does not involve control at the transcriptional and post
      transcriptional level of the c-myc gene. Finally, we showed that Stx18 is over
      expressed in clinical human breast cancer. Overall, this study showed that Stx18
      plays a role in the growth of human breast cancer cells and provided the basis
      for further investigation in determining whether it can be used as a prognostic
      marker and as a molecular target in the treatment of breast cancer.

PMID- 18722708
TI  - Intracranial internal carotid artery stenosis with vulnerable plaques
      successfully treated by stenting under cerebral protection.
AB  - Percutaneous transluminal angioplasty with stenting (PTA/stenting) for
      intracranial atherosclerotic stenoses is usually performed without any protection
      devices. We report a unique case of atherothrombotic stenosis with the vulnerable
      plaque in the cavernous portion of the internal carotid artery (ICA), which was
      successfully treated by PTA/stenting under cerebral protection with the flow
      reversal system. A 68-year-old woman presented repetitive transient ischemic
      attacks in the right ICA territory. Cerebral angiography revealed 80% stenosis in
      the cavernous portion of the right ICA. High-resolution magnetic resonance
      imaging (HR-MRI) demonstrated lipid-rich plaques at this lesion. PTA/stenting was
      performed with a proximal protection device under flow reversal. A filter device
      captured much amount of atherothrombotic debris with lipid-rich macrophages and
      leukocytes, which was consistent with HR-MRI findings. Some selected cases of
      intracranial atherothrombotic ICA stenoses may need endovascular treatment with
      cerebral protection system. HR-MRI is useful to evaluate plaque characteristics
      even in the cavernous portion of the ICA.

PMID- 18722710
TI  - Synthesis, characterization and analytical application of hybrid; acrylamide
      zirconium (IV) arsenate a cation exchanger, effect of dielectric constant on
      distribution coefficient of metal ions.
AB  - A new hybrid inorganic-organic cation exchanger acrylamide zirconium (IV)
      arsenate has been synthesized, characterized and its analytical application
      explored. The effect of experimental parameters such as mixing ratio of reagents,
      temperature, and pH on the properties of material has been studied. FTIR, TGA, X
      ray, UV-vis spectrophotometry, SEM and elemental analysis were used to determine
      the physiochemical properties of this hybrid ion exchanger. The material behaves
      as a monofunctional acid with ion-exchange capacity of 1.65 meq/g for Na(+) ions.
      The chemical stability data reveals that the exchanger is quite stable in mineral
      acids, bases and fairly stable in organic solvents, while as thermal analysis
      shows that the material retain 84% of its ion-exchange capacity up to 600 degrees
      C. Adsorption behavior of metal ions in solvents with increasing dielectric
      constant has also been explored. The sorption studies reveal that the material is
      selective for Pb(2+) ions. The analytical utility of the material has been
      explored by achieving some binary separations of metal ions on its column. Pb(2+)
      has been selectively removed from synthetic mixtures containing Mg(2+), Ca(2+),
      Sr(2+), Zn(2+) and Cu(2+), Al(3+), Ni(2+), Fe(3+). In order to demonstrate
      practical utility of the material quantitative separation of the Cu(2+) and
      Zn(2+) in brass sample has been achieved on its columns.

PMID- 18722711
TI  - Coupled acidification and ultrasound with iron enhances nitrate reduction.
AB  - Contaminated soils, especially when pollutant concentrations are high, pose
      potentially serious threats to surface and groundwater quality, when there are
      spills, discharges, or leaking storage tanks. For in situ remediation of nitrate
      in groundwater, the use of zero-valent iron (Fe(0)) is suggested. The formation
      of passivating scales on Fe(0) over time may limit the long-term reduction
      potential of Fe(0). The aim of this study was to investigate the effect of
      ultrasound and pH on the destruction of passive oxide film. Batch tests were
      conducted in a specially designed protocol using ultrasound, and changing iron
      (commercial iron powder of micro-scale grain size) loading and pH. The results
      showed deactivation of the degradation process by Fe(0) with combined
      ultrasound/iron system and with ultrasound alone. However, the degradation rate
      increases with decrease in pH. The degradation rate was 45% for pH 2 and 20% for
      pH 4. The combination of iron, acidification, and ultrasound showed excellent
      degradation efficiency, and the degradation rate was 99%. Acidification could
      destroy passive oxide film and activate iron, thus, hastening the reaction
      between Fe(0) and nitrate. Ultrasound was helpful in destroying or preventing the
      formation of passive oxide film under acidification.

PMID- 18722712
TI  - Olive mill wastewater degradation by Fenton oxidation with zero-valent iron and
      hydrogen peroxide.
AB  - The degradation of olive mill wastewater (OMW) with hydroxyl radicals generated
      from zero-valent iron and hydrogen peroxide has been investigated by means of
      chemical oxygen demand (COD) and phenolic compounds analyses. The effects of the
      H2O2 dose, the pH and the organic matter concentration have been studied. The
      optimal experimental conditions were found to have continuous presence of iron
      metal, acid pH (2.0-4.0), and relatively concentrated hydrogen peroxide (9.5M).
      Coloration of OMW disappeared and phenolic compound decreased to 50% of initial
      concentration after 3h reaction time. The application of zero-valent Fe/H2O2
      procedure permitted high removal efficiencies of pollutants from olive mill
      wastewater. The results show that zero-valent Fe/H2O2 could be considered as an
      effective alternative solution for the treatment of OMW or may be combined with a
      classical biological process to achieve high quality of effluent water.

PMID- 18722713
TI  - How should treatment results from clinical practice be reported?

PMID- 18722714
TI  - Freynhagen R et al.: Pseudoradicular and radicular low back pain--a disease
      continuum rather than different entities? Answers from quantitative sensory
      testing. Pain 2008;135:65-74.

PMID- 18722715
TI  - Children with chronic widespread pain: hunting the snark.

PMID- 18722716
TI  - Seroepidemiological study of Neospora caninum infection in dogs found in dairy
      farms and urban areas of Aguascalientes, Mexico.
AB  - The objective of this study was to describe the seroepidemiology of Neospora
      caninum infection in dogs in close contact with dairy cattle and dogs from urban
      areas of Aguascalientes, Mexico, as well as to estimate the possible association
      between age, gender and size of these groups and seroprevalence. Sera were
      obtained from samples of 152 dogs in dairy farms and 116 in the urban area, and
      were subjected to ELISA test. General seroprevalence reached 32%, while the
      seroprevalence in farm dogs (41%) was significantly higher than in dogs from the
      urban area (20%) (p<0.05). Regarding age groups, general seroprevalence was
      greater among dogs between 11 and 15 years of age (67%) remaining equal between
      males and females (32 and 31%, respectively). Nevertheless, females resident in
      farms had a higher seroprevalence (42%) than female resident in the urban area.
      Regarding size, large-sized animals had greater seroprevalence in farms (58%),
      while in the urban area medium-sized animals were those that had the highest
      seroprevalence (27%). It was found that dairy farm dogs had a higher risk of
      infection (OR=2.79; p=0.0004), and that in said group, the age range from <1 to 5
      years of age was identified as a risk factor (OR=3.11, p=0.001).

PMID- 18722717
TI  - Epidemiological and genetic characterization of Toxoplasma gondii in urban
      pigeons from the area of Lisbon (Portugal).
AB  - Circumstantial evidence suggests that birds may be a good indicator of soil
      contamination, since they feed from the ground. Therefore a study was conducted
      to assess the prevalence of Toxoplasma gondii in urban pigeons (Columba livia)
      from different areas of the city of Lisbon and to genetically characterize T.
      gondii strains isolated from infected animals, in order to assess circulating
      genotypes. Sera from 695 pigeons captured at 33 different localities of the city
      of Lisbon were assayed by the direct agglutination test (DAT) showing a 4.6%
      prevalence. One third of flocks sampled revealed to be infected with T. gondii,
      with prevalence ranging between 5% and 62.5%. T. gondii DNA could be
      characterized directly from brain tissue from 12 of 23 seropositive pigeons.
      Microsatellite typing revealed that 9 strains belonged to type II, 2 were type
      III and one was type I. No recombinant or atypical genotypes were found. Attempts
      to recover viable T. gondii strains through bioassay in mice resulted in the
      isolation of 9 strains.

PMID- 18722718
TI  - Apoptosis and non-apoptotic deaths in cancer development and treatment response.
AB  - Resistance to apoptosis is closely linked to tumorigenesis, as it enables
      malignant cells to expand even in a stressful environment. Cells resistant to
      apoptosis are also assumed to be resistant to anti-cancer therapies. Apoptosis
      has therefore taken a central position in cell death research. However, its
      contribution to treatment success is highly debated for solid tumors. It becomes
      more and more clear that cells can also die by non-apoptotic mechanisms, such as
      autophagy, mitotic catastrophe and necrosis. In this review, we summarize the
      current knowledge regarding the molecular pathways that underlie these apoptotic
      and non-apoptotic death pathways, and discuss the clinical data that have now
      accumulated to evaluate their roles in tumor development and cancer treatment.

PMID- 18722719
TI  - Low plasma tryptophan in carcinoid patients is associated with increased urinary
      cortisol excretion.
AB  - BACKGROUND: Previously we observed in patients suffering from a metastatic
      carcinoid tumor that irritability, aggression and lack of impulse control are
      associated with low levels of plasma tryptophan and presumably with low brain
      serotonin function. In rats we showed that a diet of low tryptophan resulted in
      higher stress responses and higher corticosterone production. Here we tested in
      carcinoid patients whether tryptophan depletion due to tumor 5-HT overproduction
      is associated with high cortisol production. METHODS: Urinary excretion of
      cortisol, serotonin, 5-hydroxyindole acetic acid (the main metabolite of
      serotonin a marker of tumor activity), plasma levels of tryptophan and platelet
      content of serotonin (index of peripheral serotonin synthesis) were determined in
      metastatic midgut carcinoid patients. Patients (N = 25) were divided into two
      groups based on their plasma tryptophan levels (< or = 25 micromol/l, n = 12 and
      > or = 49 micromol/l, n = 13). RESULTS: Carcinoid patients with low plasma
      tryptophan levels had significantly higher urinary excretion of free cortisol (p
      < 0.01), independent of tumor activity. The inter-individual differences in the
      low tryptophan group, however, were substantial. CONCLUSIONS: In a subgroup of
      the patients suffering from metastatic carcinoid disease the cerebral access of
      plasma tryptophan is impaired, thus rendering cerebral serotonin
      neurotransmission suboptimal and leading to hypercortisolism. The present study
      provides further support to the idea that low serotonergic function is a risk for
      developing stress-associated psychopathology.

PMID- 18722720
TI  - Anxiety vulnerability factors and disorders and tobacco and marijuana use and
      disorders: emerging theory and research explicating their relations.

PMID- 18722722
TI  - It's hard to change the water.

PMID- 18722721
TI  - A brief 7-day estimate of alcohol consumption for use in smoking cessation
      clinical trials.
AB  - Accruing evidence of an association between drinking and smoking relapse suggests
      that it is important to measure alcohol use in smoking cessation studies.
      However, most studies do not do so, often because of the extra time burden
      required for these assessments. Data from participants (N=634) in two smoking
      cessation clinical trials were used to examine the relationship between short and
      longer periods of monitoring for a number of Timeline Followback (TLFB) drinking
      metrics at baseline and during treatment. High intercorrelations were found
      between short (7 and 14 days) and longer (30 and 60 days) time windows for
      baseline drinking data. Intercorrelations between short (last 7 days of
      treatment) and longer (entire treatment period) time windows of drinking data
      during the smoking cessation treatment period were also mostly in the high range.
      Although total abstinence was significantly overestimated with shorter time
      windows, for those who were misclassified, percentage of days abstinent was high
      and percentage of heavy drinking days and number of drinks per drinking day were
      low during the longer period. Thus, a brief estimate of alcohol use over 7 days
      at baseline is likely to provide a representative assessment of percentage of
      days abstinent, percentage of heavy drinking days, and number of drinks per
      drinking day. To estimate abstinence at baseline and during treatment, however, a
      more comprehensive period of monitoring may be required.

PMID- 18722723
TI  - The effect of hyperbaric oxygen therapy on blood vessel function in diabetes
      mellitus.
AB  - Prolonged untreated diabetes mellitus leads to microangiopathy, tissue hypoxia
      and ischemic lesions; it increases the risk for stroke and exacerbates brain
      tissue damage following ischemia. Patients exhibit advanced atherosclerosis in
      coronary and cerebral arteries as well as enhanced vascular responsiveness to
      vasoconstrictors, an attenuated response to vasodilators and impaired
      autoregulation of cerebral blood flow. Altered endothelial function of arterioles
      and an impaired vasomotor function of resistance vessels could contribute to
      altered regulation of regional blood flow and insufficient tissue perfusion in
      diabetes mellitus. Hyperbaric oxygen therapy is shown to contribute to the
      healing of ischemic ulcerations in diabetic patients and to improvement of
      several other pathologic conditions. However, information about the mechanism of
      how this therapy works is still very limited. We postulate that hyperbaric oxygen
      therapy has an effect on vascular function by modulating mechanisms of vascular
      responses to various dilator and constrictor agonists in cerebral resistance
      vessels, leading to restored vascular reactivity. In accordance to this, the
      therapy affects production of vasodilators and vasoconstrictors, as well as the
      vessel-sensitivity to these factors. Furthermore, we hypothesize that hyperbaric
      oxygen therapy would restore cerebral blood flow regulation that is impaired in
      diabetics, whereas in contrast to that, chronic intermittent hypoxia would lead
      to impaired cerebral blood flow. These proposed mechanisms would, if confirmed,
      represent a valuable advancement in the understanding of this subject.

PMID- 18722725
TI  - [Outbreak of measles in Mayotte, Indian Ocean, 2005-2006].
AB  - OBJECTIVE: An outbreak of measles occurred from 2005 to 2006 in Mayotte, a French
      territory in the Indian Ocean. The aim of this study was to describe the
      outbreak, to analyze epidemiologic and sociodemographic characteristic of cases,
      and to suggest recommendations for measles surveillance and preventive measures
      in Mayotte. DESIGN: An outbreak investigation was conducted and an enhanced
      passive surveillance system of incident cases was implemented. RESULTS: During
      the outbreak, 1269 clinical cases, including 156 (12.3%) biologically confirmed
      cases, were reported. The attack rate was 0.71% and no death due to measles was
      recorded. The median age of cases was 12 years and the M/F sex-ratio 1.1.
      Teenagers and young adults (10-19 years) were the most frequently affected
      (44.4%) and infants less than one year of age accounted for 21.6% of the cases.
      In the 1269 clinical cases, 27.3% of patients had received at least one dose of
      measles vaccine before the outbreak. The immunization coverage in school children
      reached 59.1% at the end of the vaccination campaign. CONCLUSION: In the future,
      this vaccinal coverage should be improved to prevent other outbreaks, especially
      in vulnerable groups like immigrants. A surveillance system with systematical
      report of the biologically confirmed cases is needed in Mayotte.

PMID- 18722724
TI  - Predictors of violence following Emergency Department visit for cocaine-related
      chest pain.
AB  - This study examined 1-year violence outcomes among non-injured patients treated
      in the Emergency Department (ED) for cocaine-related chest pain. An urban Level I
      ED required patients with chest pain (age 60 and younger) provide a urine sample
      for cocaine testing. Cocaine-positive consenting patients (n=219) were
      interviewed in the ED; 80% completed follow-up interviews over 12-months (n=174;
      59% male, 79% African-American, mean age=38.8, standard deviation 9.06; range=19
      60). Baseline rates of past year violent victimization and perpetration history
      were: 38% and 30%, respectively. During the 12-month follow-up, rates of
      victimization and perpetration outcomes were 35% and 30%, respectively.
      Predictors of violence outcomes (either victimization or perpetration) in the
      year post-ED visit based on characteristics were measured at baseline or during
      the follow-up period (i.e., gender, age, psychological distress, binge drinking
      days, cocaine use days, marijuana use days, substance abuse/dependence diagnosis,
      victimization/perpetration history). Victimization during the follow-up was
      related to younger age, more frequent binge drinking and marijuana use at
      baseline, and victimization history, and to substance abuse/dependence, more
      frequent binge drinking, and psychiatric distress at follow-up. Specifically,
      participants who reported victimization at baseline were approximately 3 times
      more likely to report victimization at 12-month follow-up. Perpetration during
      the follow-up was related to younger age and more frequent binge drinking at
      baseline, and to substance abuse/dependence, more frequent binge drinking, and
      psychiatric distress at follow-up. Overall, no significant gender differences
      were observed in violence; however, women were more likely than men to report
      injury during the most severe partner violence incident. Violence is a common
      problem among patients presenting to an inner-city ED for cocaine-related chest
      pain, with younger age and frequency of binge drinking being a consistent marker
      of continued violence involvement. Intervention approaches to link these not-in
      treatment cocaine users to services and reduce cocaine use must take into account
      concomitant alcohol misuse and violence.

PMID- 18722726
TI  - [Current data on vaccines for respiratory diseases].
AB  - Respiratory tract infections are a major reason of antibiotic prescription. Some
      of these infections can be prevented by vaccination. In France, the main new data
      concerns the following vaccines: Haemophilus influenzae: besides the vaccine
      effectiveness H. influenzae b, that is a virulent capsulated strain, a polyvalent
      vaccine effective against non-capsulated strains, responsible for otitis media,
      is under development. Pneumococci: the conjugated heptavalent vaccine recommended
      for all infants in the USA since the year 2000 allowed a dramatic drop in the
      incidence of invasive infections and of otitis media due to pneumococci, with an
      indirect impact reducing the frequency of pneumonia in adults. Influenza: the
      vaccinal coverage remains insufficient in people targeted by recommendations,
      particularly in health care workers. New recommendations concern some travel
      agents, people living in close contact with infants at risk and women immediately
      after delivery of a newborn at risk. Pertussis: the vaccinal coverage of
      preadolescents is insufficient. Vaccination of adults is mainly recommended for
      people who are expected to be in close contact with newborns (health care
      workers, parents). Tuberculosis: BCG vaccination is no longer mandatory, but is
      now strongly recommended for all infants in the greater Paris area, French
      Guyana, and for all infants at risk, especially immigrants depending on their
      native country. Varicella: universal vaccination is not recommended. To prevent
      respiratory complications in adults, the vaccine is now recommended for all
      varicella naive teenagers.

PMID- 18722727
TI  - Radiation exposures of cancer patients from medical X-rays: how relevant are they
      for individual patients and population exposure?
AB  - X-ray procedures have a substantial impact not only on patient care but also on
      man-made radiation exposure. Since a reliable risk-benefit analysis of medical X
      rays can only be performed for diagnosis-related groups of patients, we
      determined specific exposure data for patients with the ten most common types of
      cancer. For all patients with the considered cancers undergoing medical X-ray
      procedures in a maximum-care hospital between 2000 and 2005, patient- and
      examination-specific data were retrieved from the hospital/radiology information
      system. From this data, the cumulative 5-year effective dose was estimated for
      each patient as well as the mean annual effective dose per patient and the mean
      patient observation time for each cancer site. In total, 151,439 radiographic,
      fluoroscopic, and CT procedures, carried out in 15,866 cancer patients (age, 62+/
      13 years), were evaluated. The mean 5-year cumulative dose varied between 8.6 mSv
      (prostate cancer) and 68.8 mSv (pancreas cancer). Due to an increasing use of CT
      scans, the mean annual effective dose per patient increased from 13.6 to 18.2 mSv
      during the 6-year period. Combining the results obtained in this study for a
      particular hospital with cancer incidence data for Germany, we estimated that
      cancer patients having X-ray studies constitute at least 1% of the population but
      receive more than 10% of the total effective dose related to all medical X-ray
      procedures performed nationwide per year. A large fraction of this dose is
      radiobiologically ineffective due to the reduced life expectancy of cancer
      patients.

PMID- 18722728
TI  - Computer-assisted quantification of interstitial lung disease associated with
      rheumatoid arthritis: preliminary technical validation.
AB  - PURPOSE: To validate a threshold-based prototype software application (MeVis
      PULMO 3D) for quantification of chronic interstitial lung disease (ILD) in
      patients with rheumatoid arthritis (RA) using variable threshold settings for
      segmentation of diseased lung areas. METHODS: Twenty-two patients with rheumatoid
      arthritis were included and underwent thin-section CT (4x1.25mm collimation). CT
      scans were assessed by two observers for extent of ILD (EoILD), and twice by
      MeVis PULMO 3D for each protocol. MeVis PULMO 3D used four segmentation threshold
      (ST) settings (ST=-740, -780, -800 and -840HU). Pulmonary function tests were
      obtained in all patients. Statistical evaluation used 95% limits of agreement
      (LoA) and linear regression analysis. RESULTS: There was total concordance
      between the software measurements. Interobserver agreement was good (LoA=-28.36
      to 17.58%). EoILD by readers correlated strongly with DL(CO) (r=-0.702, p<0.0001)
      and moderately with FVC (r=-0.523, p=0.018). There was close correlation between
      readers and MeVis PULMO 3D with best results for ST <780HU (EoILD vs. MeVis PULMO
      3D: r=0.650 for ST=-800 and -840HU, respectively; p=0.002). MeVis PULMO 3D
      correlated best with DL(CO) at ST of -800HU (r=-0.44, -0.49, -0.58 and -0.57 for
      ST=-740, -780, -800 and -840, respectively; p=0.007-0.05) and moderately with FVC
      (r=-0.44, -0.51, -0.59 and -0.45 for ST=-740, -780, -800 and -840), respectively;
      p=0.007-0.05). CONCLUSION: The MeVis PULMO 3D system used holds promise to become
      a valuable instrument for quantification of chronic ILD in patients with RA when
      using the threshold value of -800HU, with evidence of the closest correlations,
      both with human observers and physiologic impairment.

PMID- 18722729
TI  - Dose related, comparative evaluation of a novel bone-subtraction algorithm in 64
      row cervico-cranial CT angiography.
AB  - PURPOSE: Comparative evaluation of a low-dose scan protocol for a novel bone
      subtraction (BS) algorithm, applicable to 64-row cervico-cranial (cc) CT
      angiography (MSCTA). METHODS AND PATIENTS: BS algorithm assessment was performed
      in cadaveric phantom studies by stepwise variation of tube current and head
      malrotation using a 64-row CT scanner. In order to define minimum dose
      requirements and the rotation correction capacity, a low dose BS MSCTA protocol
      was defined and evaluated in 12 patients in comparison to a common manual bone
      removal algorithm. Standard MIPs of both modalities were evaluated in a blinded
      manner by two neuroradiologists for image quality composed, of vessel contour
      sharpness and bony vessel superposition, by using a five-point score each.
      Effective Dose (E) and data post-processing times were defined. RESULTS: In
      experimental studies prescan tube current could be cut down to one-sixth of post
      contrast scan doses without compromise of bone-subtraction whereas incomplete
      subtraction appeared from four degrees head malrotation on. Prescan E amounted to
      additional 1.1mSv (+25%) in clinical studies. BS MSCTA performed significantly
      superior in terms of bony superposition for vascular segments C3-C7 (p<0.001), V1
      V2, V3-V4 (p<0.05, p<0.001 respectively) and the ophthalmic artery (p<0.05),
      whereas vessel contour sharpness in BS MSCTA only proved superior for arterial
      segments V3-V4 (p<0.001) and C3-C7 (p<0.001). MBR MSCTA received higher ratings
      in vessel contour sharpness for C1-C2 (p<0.001), callosomarginal artery
      (p<0.001), M1, M2, M3 (p<0.001 each) and the basilar artery (p<0.001).
      Reconstruction times amounted to an average of 1.5 (BS MSCTA) and 3min (MBR
      MSCTA) respectively. CONCLUSION: The novel BS algorithm provides superior skull
      base artery visualisation as compared to common manual bone removal algorithms,
      increasing the Effective Dose by one-fourth. Yet, inferior vessel contour
      sharpness was noted intracranially, thus limiting the BS algorithm use to
      patients with suspected vessel pathology at the skull base level.

PMID- 18722730
TI  - Tracheal intubation prevented with administration of Fab antivenom after severe
      crotaline envenomation.
AB  - BACKGROUND: Crotaline snake envenomations are common, but severe crotaline
      envenomations are infrequent. Death from severe envenomation is usually from
      upper airway edema and respiratory failure. Published reports of severe
      respiratory compromise and anaphylactoid reactions are rare. Currently, FabAV
      (Crotalidae polyvalent immune Fab [Ovine] [CroFab]) is the mainstay of crotaline
      envenomation treatment; however, FabAV has been approved for only mild and
      moderate envenomations. CASE REPORT: We describe a case of a male with severe
      systemic effects and airway compromise after crotaline envenomation. The
      patient's systemic effects and upper airway edema substantially improved after
      antivenom infusion and before epinephrine administration. Endotracheal intubation
      was averted, clinical deterioration was avoided, and improvement occurred after
      prompt FabAV use. CONCLUSION: Fab antivenom likely prevented endotracheal
      intubation in our case of severe crotaline envenomation.

PMID- 18722731
TI  - Bronchogenic cyst.

PMID- 18722732
TI  - Application of lean manufacturing techniques in the Emergency Department.
AB  - BACKGROUND: "Lean" is a set of principles and techniques that drive organizations
      to continually add value to the product they deliver by enhancing process steps
      that are necessary, relevant, and valuable while eliminating those that fail to
      add value. Lean has been used in manufacturing for decades and has been
      associated with enhanced product quality and overall corporate success.
      OBJECTIVES: To evaluate whether the adoption of Lean principles by an Emergency
      Department (ED) improves the value of emergency care delivered. METHODS:
      Beginning in December 2005, we implemented a variety of Lean techniques in an
      effort to enhance patient and staff satisfaction. The implementation followed a
      six-step process of Lean education, ED observation, patient flow analysis,
      process redesign, new process testing, and full implementation. Process redesign
      focused on generating improvement ideas from frontline workers across all
      departmental units. Value-based and operational outcome measures, including
      patient satisfaction, expense per patient, ED length of stay (LOS), and patient
      volume were compared for calendar year 2005 (pre-Lean) and periodically after
      2006 (post-Lean). RESULTS: Patient visits increased by 9.23% in 2006. Despite
      this increase, LOS decreased slightly and patient satisfaction increased
      significantly without raising the inflation adjusted cost per patient.
      CONCLUSIONS: Lean improved the value of the care we delivered to our patients.
      Generating and instituting ideas from our frontline providers have been the key
      to the success of our Lean program. Although Lean represents a fundamental change
      in the way we think of delivering care, the specific process changes we employed
      tended to be simple, small procedure modifications specific to our unique people,
      process, and place. We, therefore, believe that institutions or departments
      aspiring to adopt Lean should focus on the core principles of Lean rather than on
      emulating specific process changes made at other institutions.

PMID- 18722733
TI  - Giant sublingual sialolith leading to dysphagia.

PMID- 18722734
TI  - Prehospital transport time intervals for acute stroke patients.
AB  - BACKGROUND: Recognizing factors that cause prehospital stroke delays may improve
      time of presentation to the Emergency Department (ED) and allow earlier treatment
      of acute stroke patients. STUDY OBJECTIVES: To determine the impact of stroke
      recognition by emergency medical dispatchers (EMD) and paramedics (PM) on ED
      arrival time in a large urban Emergency Medical Services system. METHODS:
      Retrospective study of patients aged 18 years or more identified as having acute
      stroke by EMD, PM, or stroke neurologists from January 1, 2005 to December 31,
      2005. Data were acquired from computer-assisted dispatch records, paramedic
      assessments, ICD-9 (International Classification of Diseases, 9(th) Revision)
      databases, and a hospital stroke registry. Paramedic time to scene, scene time,
      and total run time were computed for patients with final hospital diagnosis of
      stroke and grouped into missed strokes and identified strokes by EMD and PM. Time
      intervals were compared between missed and identified strokes as well as between
      incidents where EMD and PM agreed or disagreed. RESULTS: A total of 1067 patients
      were eligible for the study; 22 were excluded for missing data. For true strokes,
      EMD and PM were in agreement 27.3% of the time. The median RT was 2.5 min shorter
      when there was agreement between the providers than when there was disagreement
      (36.5 min; interquartile range [IQR] 30-43 vs. 39 min.; IQR 33-45, respectively).
      CONCLUSIONS: Prehospital scene time and run times for acute strokes are less when
      there is diagnostic concordance between dispatchers and paramedics. Time
      intervals did not differ between missed and recognized strokes.

PMID- 18722735
TI  - Biliary causes of postcholecystectomy syndrome.
AB  - BACKGROUND: The postcholecystectomy syndrome refers to the persistence of
      gastrointestinal symptoms after cholecystectomy; patients with this syndrome
      commonly seek treatment in the Emergency Department (ED). There are a multitude
      of biliary and non-biliary causes of postcholecystectomy syndrome. OBJECTIVES: To
      review the biliary causes of postcholecystectomy syndrome and present a suggested
      diagnostic workup. DISCUSSION: A number of biliary causes are discussed,
      including choledocholithiasis, bile duct injury and biliary leaks, cystic duct
      and gallbladder remnants, sphincter of Oddi dysfunction, and biliary ascariasis.
      The ED workup should focus on differentiating biliary from non-biliary causes of
      the patient's symptoms. CONCLUSION: A right upper quadrant abdominal ultrasound,
      liver transaminases, alkaline phosphatase, and serum bilirubin are the tests most
      useful in the ED for making this distinction and determining the most appropriate
      treatment and disposition of the patient. Computed tomography may be of use in
      the initial post-operative period.

PMID- 18722736
TI  - Trapped lung syndrome.

PMID- 18722737
TI  - Anxiety and depressive disorders in patients presenting with chest pain to the
      emergency department: a comparison between cardiac and non-cardiac origin.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of anxiety and
      depressive disorders in patients presenting with chest pain to the Emergency
      Department (ED) and determine if there is a relationship between these and
      cardiac vs. non-cardiac chest pain. METHODS: This prospective cross-sectional
      study was performed in an urban tertiary care hospital between March and October
      2005. Consecutive patients presenting with chest pain were enrolled in the study.
      The prevalence of anxiety and depressive disorders in patients with chest pain
      were determined by using the Hospital Anxiety and Depression Scale. RESULTS: A
      total of 324 patients presented to the ED with chest pain during the study
      period. The mean age of the patients studied was 50.5 +/- 14 years; 67% were men
      and 33% were women. Of the 324 study patients, 194 (59.9%) patients were
      diagnosed with non-cardiac chest pain, 16 (4.9%) with stable angina, 84 (25.9%)
      with unstable angina, and 30 (9.3%) with acute myocardial infarction. No
      statistically significant differences were determined between patients with
      cardiac and non-cardiac chest pain both for anxiety (40% vs. 38.1%, respectively;
      p = 0.737) and depressive disorders (52.3% vs. 52.1%, respectively; p = 0.965).
      CONCLUSION: Anxiety and depressive disorders are common among patients presenting
      with chest pain to the ED. However, the prevalence of anxiety and depressive
      disorders is similar between patients with chest pain of cardiac and non-cardiac
      origin. Chest pain should not be attributed to an anxiety or depressive disorder
      before organic etiologies are excluded.

PMID- 18722738
TI  - Live twin ectopic pregnancy with advanced gestation.

PMID- 18722739
TI  - Rectus sheath hematoma caused by non-contact strenuous exercise mimicking acute
      appendicitis.
AB  - A healthy 26-year-old man visited the Emergency Department due to right lower
      quadrant pain of 2 days' duration that developed after wakeboarding. There was no
      history of direct trauma to the abdomen. Physical examination revealed tenderness
      and rebound tenderness on the right lower quadrant area. There was no palpable
      abdominal mass. Computed tomography (CT) of the abdomen was undertaken to discern
      the causes of acute abdomen, including acute appendicitis. CT revealed a small
      size rectus sheath hematoma beneath the lower end of the right rectus muscle. The
      patient was admitted for supportive care including pain control and was
      discharged with improvement after 5 days. Rectus sheath hematoma can be caused by
      not only a direct blow but also non-contact strenuous exercise, for example,
      wakeboarding in this case. Although the majority of rectus sheath hematomas are
      self-limiting, some can cause peritoneal irritation signs, mimicking acute
      abdomen, and eventually lead to unnecessary laparotomy without clinical suspicion
      and ancillary tests including CT scan and ultrasonography.

PMID- 18722740
TI  - Clinical analysis of hyponatremia in acute craniocerebral injury.
AB  - OBJECTIVE: To explore pathological mechanisms of central hyponatremia and its
      treatment. METHODS: Synchronous assay was made for changes of atrial natriuretic
      peptide (ANP), brain natriuretic peptide (BNP), endogenous digitalis-like
      substance (EDLS), antidiuretic hormone (ADH) in blood, and Na(+) concentrations
      in blood and urine, and plasma- and urine-osmolality in 68 patients with acute
      craniocerebral injury (ACI). RESULTS: Of the 68 patients with ACI, 27 were found
      to have hyponatremia, and such illness was mostly concentrated on severe cases.
      CONCLUSIONS: The central hyponatremia in patients with ACI may be related to the
      increase in the secretion of EDLS and ADH as the result of damaged functions of
      the hypothalamic-hypophysial system, and it seems that the decrease in blood ANP
      and BNP has no direct effect on Na(+) concentrations in blood. Inappropriate
      secretion of antidiuretic hormone syndrome and cerebral salt-wasting syndrome are
      the two main reasons for hyponatremia in patients with craniocerebral injury. The
      pathological mechanism, diagnostic standards, as well as treatment methods for
      the two, however, are not just the same. Intravenous injection of extrinsic
      thyrotropin-releasing hormone might inhibit dilutional hyponatremia arising from
      the increase in ADH secretion by patients with ACI.

PMID- 18722741
TI  - A 52-year-old man with malaise and a petechial rash.
AB  - BACKGROUND: Capnocytophaga canimorsus is a Gram-negative, fusiform, rod-shaped
      organism that is part of the normal oral flora of dogs, cats, and other animals.
      A significant number of Emergency Department (ED) patients are surgically or
      functionally asplenic and may be at marked risk for overwhelming post-splenectomy
      infection (OPSI). OPSI has a mortality rate estimated to be up to 70%. The risk
      of sepsis is estimated to be 30-60 times greater after splenectomy, and C.
      canimorsus is one of the organisms that can cause catastrophic OPSI. OBJECTIVES:
      To describe a case of C. canimorsus septic shock in a post-splenectomy patient
      and review the epidemiology of OPSI, the role of the spleen in protecting the
      body from infection, and the potential role of early goal-directed therapy in the
      resuscitation of patients with OPSI. CASE REPORT: A 52 year-old man with a past
      medical history significant for idiopathic thrombocytopenic purpura (status post
      splenectomy), and non-Hodgkin lymphoma (treated for cure), was brought to the ED
      with the chief complaints of light-headedness, malaise, and a rapidly spreading
      rash. He was found to be hypotensive, tachycardic, and tachypneic, and had a
      marked lactic acidosis. He was aggressively resuscitated with large volume fluid
      resuscitation and treated empirically with broad-spectrum antibiotics for septic
      shock of unclear etiology. His clinical course was complicated by acute lung
      injury and renal failure. Blood cultures grew C. canimorsus; he was extubated on
      hospital day 7 and discharged home several days later in good condition.
      CONCLUSIONS: Patients status-post-splenectomy are at greatly increased risk for
      infection from encapsulated organisms and other organisms, including C.
      canimorsus, which is part of the normal oral flora of dogs, cats, and other
      animals. It can be spread to humans by bites, scratches, or less invasive forms
      of animal-human contact. C. canimorsus infection can lead to OPSI. Early
      recognition and aggressive clinical management, including early goal-directed
      therapy and rapid administration of antibiotics, may minimize the morbidity and
      mortality of this condition and other etiologies of severe sepsis and septic
      shock.

PMID- 18722742
TI  - Methicillin-resistant Staphylococcus aureus sepsis presenting with septic
      pulmonary emboli.
AB  - BACKGROUND: Septic pulmonary emboli are the result of infections that typically
      originate from an extrapulmonary source. Septic pulmonary embolus is a rare
      disorder that classically presents with fever, respiratory symptoms, and lung
      infiltrates. OBJECTIVES: Our objective is to share our experience of a rare
      diagnosis that was the result of a very common bacterium seen in the Emergency
      Department (ED). CASE REPORT: We present a case of methicillin-resistant
      Staphylococcus aureus (MRSA) sepsis presenting as bilateral septic pulmonary
      emboli in a patient with undiagnosed acquired immunodeficiency syndrome. A 29
      year-old Hispanic man presented to our ED with a history of abdominal pain and
      vomiting for 3 days and new onset of shortness of breath. The patient was seen 2
      weeks prior for a simple abscess incision and drainage and was treated with
      trimethoprim/sulfamethoxazole. On the day of admission, a helical computed
      tomography scan of the chest was obtained, which revealed bilateral septic
      pulmonary emboli. The patient was admitted for intravenous antibiotic therapy and
      was subsequently found to have MRSA sepsis. CONCLUSION: Septic pulmonary embolus
      is a rare finding that is most commonly seen in patients who are
      immunocompromised. The patient fully recovered after aggressive antibiotic
      therapy.

PMID- 18722743
TI  - Comparison of traditional advanced cardiac life support (ACLS) course instruction
      vs. a scenario-based, performance oriented team instruction (SPOTI) method for
      Korean paramedic students.
AB  - Current Advanced Cardiac Life Support (ACLS) course instruction involves a 2-day
      course with traditional lectures and limited team interaction. We wish to explore
      the advantages of a scenario-based performance-oriented team instruction (SPOTI)
      method to implement core ACLS skills for non-English-speaking international
      paramedic students. The objective of this study was to determine if scenario
      based, performance-oriented team instruction (SPOTI) improves educational
      outcomes for the ACLS instruction of Korean paramedic students. Thirty Korean
      paramedic students were randomly selected into two groups. One group of 15
      students was taught the traditional ACLS course. The other 15 students were
      instructed using a SPOTI method. Each group was tested using ACLS megacode
      examinations endorsed by the American Heart Association. All 30 students passed
      the ACLS megacode examination. In the traditional ACLS study group an average of
      85% of the core skills were met. In the SPOTI study group an average of 93% of
      the core skills were met. In particular, the SPOTI study group excelled at
      physical examination skills such as airway opening, assessment of breathing,
      signs of circulation, and compression rates. In addition, the SPOTI group
      performed with higher marks on rhythm recognition compared to the traditional
      group. The traditional group performed with higher marks at providing proper drug
      dosages compared to the SPOTI students. However, the students enrolled in the
      SPOTI method resulted in higher megacode core compliance scores compared to
      students trained in traditional ACLS course instruction. These differences did
      not achieve statistical significance due to the small sample size.

PMID- 18722744
TI  - Emergency ultrasound usage among recent emergency medicine residency graduates of
      a convenience sample of 14 residencies.
AB  - BACKGROUND: Emergency Medicine (EM) residency graduates are trained to perform
      Emergency Medicine bedside ultrasound (EMBU). However, the degree to which they
      use this skill in their practice after graduation is unknown. OBJECTIVES: We
      sought to test the amount and type of usage of EMBU among recent residency
      graduates, and how usage and barriers vary among various types of EM practice
      settings. METHODS: Graduates from 14 EM residency programs in 2003-2005 were
      surveyed on their current practice setting and use of EMBU. RESULTS: There were
      252 (73%) graduates who completed the survey. Of the 73% of respondents reporting
      access to EMBU, 98% had used it within the past 3 months. Access to EMBU was
      higher in academic (97%) vs. community teaching (79%) vs. community non-teaching
      settings (62%) (p < 0.001), and in Emergency Departments (EDs) where yearly
      census exceeded 60,000 visits (87% vs. 65%, p < 0.001). Physicians in academic
      settings reported "high use" of EMBU more frequently than those in community
      settings for most modalities. FAST (focused assessment by sonography in trauma)
      was the most common high-use application and the most useful in practice. The
      greatest impediment to EMBU use was "not enough time" (61%). CONCLUSIONS:
      Ultrasound usage among recent EM residency graduates is significantly higher in
      teaching than in community settings and in high-volume EDs. Its use is more
      widespread than in previous reports in all types of practice. There is a wide
      range of utilization of ultrasound in the various applications in emergency
      practice, with the evaluation of trauma being the most common.

PMID- 18722745
TI  - "Seeing is believing, and believing is seeing": an exploration of the meaning and
      impact of women's mental images of their breast cancer and their potential
      origins.
AB  - OBJECTIVE: To explore the nature, meaning and perceived origin of women's mental
      images of their breast cancer. METHODS: Fifteen women, who had completed
      treatment for primary breast cancer, participated in this qualitative in-depth
      interview study. Data were analysed using a constant comparative technique within
      the "Framework" method. RESULTS: Almost all women had a mental image of their
      cancer. Images reflected their beliefs about their illness (its appearance,
      character and dangerousness) and appeared to be related to a number offears and
      concerns. The origin of images was uncertain but appeared to be influenced by
      scan images, verbal metaphors presented by health professionals, and previous
      beliefs held about cancer. Some women used metaphors presented to infer
      properties of the cancer that may have been unintended by the health
      professional. CONCLUSION: Women may have mental images of their breast cancer
      that are associated with hope, reassurance, anxiety, despair, or views about the
      future. Further longitudinal research is required to establish the origin and
      importance of these images. PRACTICE IMPLICATIONS: Health professionals may find
      that exploring women's mental images of their cancer is a helpful way of
      identifying potential misunderstandings about their illness.

PMID- 18722746
TI  - Pre-hepatectomy portal vein embolization: single center experience.
AB  - AIM: To evaluate the feasibility and the effectiveness of portal vein
      embolization (PVE) as preoperative treatment in patients scheduled to undergo
      right hepatectomy, when the volume of the future remnant liver (FRL) appears to
      be insufficient to prevent the risk of post-surgical hepatic failure. MATERIALS
      AND METHODS: Thirty-one consecutive patients (19 men, 12 women; age range: 54-77
      years; mean age: 66.2 years) with liver malignancy (7 hepatocellular carcinoma,
      13 metastases, 9 cholangiocarcinoma, and 2 gallbladder carcinoma) were selected
      after clinical-radiological evaluation for PVE. After the embolization changes in
      volume of FRL, portal pressure, liver enzymes, and complications before and after
      hepatectomy were assessed. RESULTS: PVE was successful in all patients without
      major complications. The mean volume of FRL, calculated before and 4 weeks after
      PVE, increased from 319.2 +/- 45.1 to 460.2 +/- 27.7 cm(3) (+44.2%) in the non
      cirrhotic group and from 458.4 +/- 38.3 to 605.2 +/- 27 cm(3) (+32.1%) in the
      cirrhotic group. The FRL/TELV ratio increased by 9%. CONCLUSION: In our
      experience, PVE resulted feasible, safe, with a very low rate of complications,
      and effective to induce liver regeneration before right hepatectomy in patients
      with liver malignancy.

PMID- 18722747
TI  - Effectiveness of preoperative concurrent chemoradiation therapy (CCRT) for
      locally advanced adenocarcinoma of cervix.
AB  - AIM: To determine the efficacy of preoperative concurrent chemoradiation therapy
      (CCRT) to improve the prognosis of locally advanced adenocarcinoma of the uterine
      cervix. METHODS: Twenty-five patients with clinical stage IB2-IVB adenocarcinoma
      of the cervix were received preoperative CCRT. The CCRT protocol included:
      external radiotherapy to the pelvis: 39.6 Gy; intra-arterial or intravenous
      infusion of 70 mg/m2 cisplatin, days 1 and 22; 24-h continuous intravenous
      infusion of 700 mg/m2 5-FU, days 1-4 and 22-25. Two weeks after the end of CCRT,
      patients underwent restaging followed by appropriate surgery with pelvic
      lymphadenectomy. RESULTS: The overall clinical response rate was 96% (24/25),
      with a complete response (CR) in 12/25 patients and partial response (PR) in
      12/25. On pathological examination, 5 of 19 patients (26%) undergoing surgery
      showed a pathological CR, 13 patients showed a PR, and 1 patient no change (NC)
      in their disease. Grade 3 or 4 hematological toxicity was observed in 15
      patients. Grade 3 gastrointestinal toxicity was observed in 8 patients. The
      median follow-up period was 34 months (range, 6-69). The 5-year overall survival
      (OS) rate was 84%, and the progression-free survival (PFS) rate was 76%.
      CONCLUSIONS: Preoperative CCRT improves the survival of patients with locally
      advanced adenocarcinoma of the cervix, with manageable toxicities.

PMID- 18722748
TI  - Using national health policies to improve access to palliative care medications
      in the community.
AB  - Access to affordable priority palliative care medicines needs to be informed by
      good clinical data from well-conducted clinical trials designed to address
      efficacy, cost-effectiveness, and safety. Availability of priority palliative
      care symptom control medicines improves the provision of palliation in the place
      of patient's choice including the community. Within Australia, a National
      Medicines Policy and a Palliative Care Strategy endorsed by Federal and State and
      Territory health ministers have facilitated a process to improve the evidence for
      palliative clinical practice and, through this, improve community availability of
      key medications for people at the end of life. The initiative, coordinated by a
      working party under government auspices, has brought together medicine
      regulators, the pharmaceutical industry, government, policy makers, and
      clinicians. The brief was to improve availability of key palliative care
      medications within the current national drug regulatory and funding frameworks.
      The results to date include: a palliative care section within the Pharmaceutical
      Benefits Scheme generating the first ever patient-defined section; medicines not
      previously listed now available; commitment of AU$9.46 M for a national multisite
      collaborative clinical study network to improve the evidence for clinical
      interventions in the palliative care setting through systematic investigation
      with rigorous Phase III and IV studies to inform registration and subsidy
      applications; and establishing a national Communication Network of the Palliative
      Care Medications Working Group for the health workforce and community to improve
      the quality use where improved access has been achieved.

PMID- 18722750
TI  - Efficient interactive 3D Livewire segmentation of complex objects with arbitrary
      topology.
AB  - We present a novel interactive method based on a 3D Livewire approach for
      segmenting complex objects of arbitrary topologies. Our proposed technique
      automatically and seamlessly handles objects with branchings, concavities,
      protrusions, and non-spherical topologies with minimal user-input. Given sparse
      interactively segmented contours on orthogonal slices, our proposed method
      determines Livewire seedpoints on all slices in the third orthogonal direction,
      which are used to mimic user-guided segmentation. In doing so, our method pre
      processes these points to increase algorithm robustness, and uses a novel
      seedpoint sorting method using ideas from L-system's Turtle algorithm. Moreover,
      we present a segmentation tool based on our proposed framework and demonstrate
      the robustness of our approach on real medical data. Results highlight the
      superior performance of the proposed method with validation tests on synthetic
      and real MRI and CT data, with segmentation reproducibility exceeding 95% and
      segmentation task time decreasing to less than 20% when compared to performing 2D
      Livewire on each volume slice.

PMID- 18722749
TI  - Simple counts of ADL dependencies do not adequately reflect older adults'
      preferences toward states of functional impairment.
AB  - OBJECTIVE: To use unweighted counts of dependencies in activities of daily living
      (ADLs) to assess the impact of functional impairment requires an assumption of
      equal preferences for each ADL dependency. To test this assumption, we analyzed
      standard gamble (SG) utilities of single and combination ADL dependencies among
      older adults. STUDY DESIGN AND SETTING: Four hundred older adults used multimedia
      software (FLAIR1) to report SG utilities for their current health and
      hypothetical health states of dependency in each of 7 ADLs and 8 of 30
      combinations of ADL dependencies. RESULTS: Utilities for health states of
      multiple ADL dependencies were often greater than for states of single ADL
      dependencies. Dependence in eating, which is the ADL dependency with the lowest
      utility rating of the single ADL dependencies, ranked lower than 7 combination
      states. Similarly, some combination states with fewer ADL dependencies had lower
      utilities than those with more ADL dependencies. These findings were consistent
      across groups by gender, age, and education. CONCLUSION: Our results suggest that
      the count of ADL dependencies does not adequately represent the utility for a
      health state. Cost-effectiveness analyses and other evaluations of programs that
      prevent or treat functional dependency should apply utility weights rather than
      relying on simple ADL counts.

PMID- 18722751
TI  - Automatic segmentation of liver PET images.
AB  - Automation of liver positron emission tomography (PET) image segmentation is
      proposed in this paper. A new active contour model (ACM), called Poisson Gradient
      Vector Flow (PGVF), with genetic algorithm (GA) constructs a scheme to
      automatically find the contour of liver in the PET images. PET is widely used for
      the clinical purpose, but image quality of PET makes the image segmentation be a
      tough work. Three image data sets are tested for evaluating the new segmentation
      approach of liver PET images. One image data set is adapted from the study of one
      person with a normal liver. The other two image data sets are adapted from the
      studies of two patients with abnormal livers. The results show that the regions
      of interest (ROI) of liver are automatically segmented from the images of three
      data sets.

PMID- 18722752
TI  - Twin pregnancy and the risk of schizophrenia.
AB  - BACKGROUND: Twins are exposed to intrauterine environments that differ
      significantly from those of singletons. These diverse environments might alter
      the risk for schizophrenia in twins and make it difficult to generalize from
      findings in twins when studying the risk of schizophrenia in the general
      population. Previous studies report contradictory findings on the risk for
      schizophrenia in twins. METHODS: We studied the incidence of schizophrenia
      spectrum disorders, ascertained from Israel's National Psychiatric Registry, in a
      cohort of 2124 twins and 87,955 singletons. These offspring were followed from
      their birth in 1964-76 in the Jerusalem Perinatal study. Cox proportional hazards
      methods were used to compare outcomes over 28-41 years, adjusting for ages of
      parents. RESULTS: Twins showed a relative risk [RR] of .84 relative to
      singletons, with a 95% confidence interval [CI] of (.51-1.4). RRs and CIs for
      males and females were .68 [.34-1.4] and 1.1 [.55-2.2] respectively. Twins in
      male-male, female-female or opposite-sex sets showed no significant variation in
      RRs; furthermore, first- or second-born twins did not differ significantly from
      each other. Siblings of twins had the same risk of schizophrenia as siblings of
      singletons. CONCLUSION: Twins have the same risk for schizophrenia as the general
      population.

PMID- 18722753
TI  - Chemical peeling and microdermabrasion of the skin: comparative
      immunohistological and ultrastructural studies.

PMID- 18722754
TI  - Biodistribution of colloidal gold nanoparticles after intravenous administration:
      effect of particle size.
AB  - Purpose of the present research work was to evaluate the biological distribution
      of differently size gold nanoparticles (NP) up on intravenous administration in
      mice. Another objective was to study effect of particle size on biological
      distribution of gold NP to enable their diverse applications in nanotechnology.
      Gold NP of different particle sizes, mainly 15, 50, 100 and 200 nm, were
      synthesized by modifying citrate ion concentration. Synthesized gold
      nanoparticles were characterized by SEM and their size distribution was studied
      by particle size analyzer. Gold NP was suspended in sodium alginate solution
      (0.5%, w/v) and administered to mice (1g/kg, intravenously) [n=3]. After 24h of
      administration of gold NP, blood was collected under light ether anesthesia, mice
      were sacrificed by cervical dislocation and various tissues/organs were removed.
      The tissues were then washed with saline, homogenized and lysed with aqua regia.
      The determination of gold in samples was carried out quantitatively by
      inductively coupled plasma mass spectrometry (ICP-MS). SEM study revealed
      spherical morphology of gold NP with narrow particle size distribution.
      Biodistribution study revealed gold NPs of all sizes were mainly accumulated in
      organs like liver, lung and spleen. The accumulation of gold NP in various
      tissues was found to be depending on particle size. 15 nm gold NP revealed higher
      amount of gold and number of particles in all the tissues including blood, liver,
      lung, spleen, kidney, brain, heart, stomach. Interestingly, 15 and 50 nm gold NP
      were able to pass blood-brain barrier as evident from gold concentration in
      brain. Two-hundred nanometers gold NP showed very minute presence in organs
      including blood, brain, stomach and pancreas. The results revealed that tissue
      distribution of gold nanoparticles is size-dependent with the smallest 15 nm
      nanoparticles showing the most widespread organ distribution.

PMID- 18722755
TI  - [Cleft lip and palate: indications for radiological postnatal explorations].
AB  - AIM: We evaluated the utility of systematic neonatal radiological explorations in
      20 instances of isolated cleft lip and palate in 20 cases. METHODS: This study
      included 13 infants with prenatal ultrasound diagnosis. The type of cleft and
      possible associated anomalies were noted. A systematic chromosomal test was done.
      In 7 cases, the cleft lip was noted at birth. Postnatal outcome was obtained and
      a clinical examination and radiological explorations were carried out. RESULTS:
      For the cases with prenatal diagnosis, the chromosomal test was normal in 11
      cases and we noted associated anomalies in three cases. For the cases with
      neonatal diagnosis, the chromosomal test was normal in 6 cases and 1 infant had
      associated anomalies. CONCLUSIONS: The biological and radiological explorations
      can be numerous. In our study, the systematic neonatal radiological explorations
      did not find more elements compared with neonatal clinical examinations. The high
      risk of having a chromosomal anomaly in children with cleft lip requires
      systematic prenatal chromosomal exploration.

PMID- 18722757
TI  - Model-based analysis of myocardial strain data acquired by tissue Doppler
      imaging.
AB  - OBJECTIVE: Tissue Doppler imaging (TDI) is commonly used to evaluate regional
      ventricular contraction properties through the analysis of myocardial strain.
      During the clinical examination, a set of strain signals is acquired concurrently
      at different locations. However, the joint interpretation of these signals
      remains difficult. This paper proposes a model-based approach in order to assist
      the clinician in making an analysis of myocardial strain. METHODS AND MATERIALS:
      The proposed method couples a model of the left ventricle, which takes into
      account cardiac electrical, mechanical and hydraulic activities with an adapted
      identification algorithm, in order to obtain patient-specific model
      representations. The proposed model presents a tissue-level resolution, adapted
      to TDI strain analysis. The method is applied in order to reproduce TDI strain
      signals acquired from two healthy subjects and a patient presenting with dilated
      cardiomyopathy (DCM). RESULTS: The comparison between simulated and experimental
      strains for the three subjects reflects a satisfying adaptation of the model on
      different strain morphologies. The mean error between real and synthesized
      signals is equal to 2.34% and 2.09%, for the two healthy subjects and 1.30% for
      the patient suffering from DCM. Identified parameters show significant electrical
      conduction and mechanical activation delays for the pathologic case and have
      shown to be useful for the localization of the failing myocardial segments, which
      are situated on the anterior and lateral walls of the ventricular base.
      CONCLUSION: The present study shows the feasibility of a model-based method for
      the analysis of TDI strain signals. The identification of delayed segments in the
      pathologic case produces encouraging results and may represent a way to better
      utilize the information included in strain signals and to improve the therapy
      assistance.

PMID- 18722758
TI  - Selective axillary node sampling and radiotherapy to the axilla in the management
      of breast cancer.
AB  - AIMS: Axillary treatment for patients with early-stage breast cancer can be
      associated with considerable morbidity. Techniques, such as axillary node
      sampling (ANS) and, more recently, sentinel node biopsy, in combination with
      radiotherapy have the potential to reduce toxicity. A retrospective review of
      axillary treatment in patients with early-stage breast cancer treated at our
      institution between 1997 and 2003 was carried out to assess the outcome and
      morbidity of ANS in combination with radiotherapy. MATERIALS AND METHODS: The
      treatment policy was to carry out four-node, Edinburgh-style ANS except in those
      cases with either palpably enlarged nodes or cytological confirmation of
      involvement or with clinically obvious node involvement at surgery when level 2
      axillary node clearance (ANC) was carried out. Patients with involved nodes after
      ANS received postoperative axillary radiotherapy. RESULTS: In total, 381 patients
      were included, 331 received ANS and 50 received ANC. The median follow-up was 6.5
      years and overall survival at 5 years was 84%. Pathologically involved nodes were
      found in 152/331 (50%) ANS patients and 43/50 (86%) ANC patients. The rate of
      local recurrence (breast or chest wall) at 5 years was 4% (95% confidence
      interval 1-17%) in the ANC group and 2% (95% confidence interval 1-4%) in the ANS
      group. The nodal recurrence rate of those undergoing ANS was 3% (11/331) compared
      with 6% (3/50) for those treated by ANC. The rate of clinically significant
      lymphoedema at 5 years was significantly higher (P=0.01) in the ANC arm: 18% (95%
      confidence interval 9-32%) compared with 5% (95% confidence interval 3-8%) in
      those treated by ANS. Thirty-one cases received additional supraclavicular fossa
      irradiation because of the involvement of more than four nodes on ANS, which may
      not have been available with sentinel node biopsy and has implications for
      current practice. CONCLUSIONS: Selective ANS with the removal of a minimum of
      four nodes guides optimal locoregional treatment with good local control rates,
      low overall morbidity and may obviate the need for a second surgical procedure.

PMID- 18722759
TI  - Cartilage differentiation in cephalopod molluscs.
AB  - Amongst the various metazoan lineages that possess cartilage, tissues most
      closely resembling vertebrate hyaline cartilage in histological section are those
      of cephalopod molluscs. Although elements of the adult skeleton have been
      described, the development of these cartilages has not. Using serial histology of
      sequential developmental stages of the European cuttlefish, Sepia officinalis, we
      investigate these skeletal elements and offer the first description of the
      formation of any cellular invertebrate cartilage. Our data reveal that cuttlefish
      cartilage most often differentiates from uncondensed mesenchymal cells near the
      end of embryonic development, but that the earliest-forming cartilages
      differentiate from a cellular condensation which goes through a protocartilage
      stage in a manner typical of vertebrate primary cartilage formation. We further
      investigate the distribution and degree of differentiation of cartilages at the
      time of hatching in an additional four cephalopod species. We find that the
      timing of cartilage development varies between elements within a single species,
      as well as between species. We identify a tendency towards cartilage
      differentiation from uncondensed connective tissue in elements that form at the
      end of embryogenesis or after hatching. These data suggest a form of metaplasia
      from connective tissue is the ancestral mode of cartilage formation in this
      lineage.

PMID- 18722760
TI  - Assessment of benefits and risks of landfill materials for agriculture in
      Eritrea.
AB  - In Eritrea, farmers have applied landfill materials as fertiliser to their fields
      for several decades. A sampling scheme in the landfill site of Asmara and
      selected farmers' fields was carried out to investigate the benefits and risks of
      using landfill materials for agriculture. Soil samples were collected from
      farmers' fields (7 samples) and from the Asmara landfill site (12 samples). The
      samples were analysed for major plant nutrients, heavy metals (Cd, Cr, Cu, Pb,
      Ni, Hg and Zn), and some physical properties. Nearly 65% (by weight) of the total
      landfill material mined from the landfill site constituted waste fractions of
      various substances. The remaining 35% was composed of soil-like materials, which
      are apparently used to fertilize agricultural soils. The average organic matter,
      total nitrogen, and available phosphorus contents of soils with landfill material
      measured 2.4%, 0.13%, and 45 mg kg(-1), respectively. However, soils without
      landfill material consisted of 1.1 % organic matter, 0.04% total N, and <40 mg
      kg(-1) of available P. Except for Hg, all the other heavy metals in the landfill
      site showed values above the permissible limits. In particular, the average
      concentrations of Cu (913 mg kg(-1)) and Pb (598 mg kg(-1)) in the landfill site
      were nine-fold and four-fold greater than the allowable limits, respectively. It
      is, therefore, suggested that composting fresh organic wastes should be
      considered and tested as an alternative material for fertilising agricultural
      soils and to maintain the quality of the environment.

PMID- 18722761
TI  - Functional characterization of PorB class II porin from Neisseria meningitidis
      using a tethered bilayer lipid membrane.
AB  - PorB class II from Neisseria meningitidis is a pore-forming, outer-membrane
      protein that can translocate to the host-cell membrane during Neisserial
      infections. This report describes development of tethered bilayer lipid membrane
      (tBLM) system to measure PorB conductance properties. The tBLM was fabricated by
      depositing a self-assembled monolayer of 1,2-dipalmitoyl-sn-glycero-3
      phosphothioethanol (DPPTE) tethering lipid on a gold electrode and then using 1,2
      dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes to deposit the upper tBLM
      leaflet. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV)
      were used to monitor tBLM formation and subsequent PorB incorporation. The highly
      insulating tBLM exhibited a membrane resistance and capacitance of 2.5MOmegacm(2)
      and 0.7 microF/cm(2), respectively. PorB was incorporated into the tBLM in an
      active conformation, as evidenced by its mediation of ion passage and the
      decrease in membrane impedance. After PorB incorporation, the membrane resistance
      decreased to 0.6MOmegacm(2). As expected, the PorB channel was found to be non
      selective, allowing the transport of both cations and anions. Cyclic voltammetry
      indicated that ferricyanide ions can also pass through the pores. The PorB
      containing biomimetic interface developed in this study could potentially be used
      to screen for compounds that modulate PorB activity.

PMID- 18722762
TI  - CdTe nanocrystal-based electrochemical biosensor for the recognition of
      neutravidin by anodic stripping voltammetry at electrodeposited bismuth film.
AB  - CdTe quantum dots (QDs)-based electrochemical sensor for recognition of
      neutravidin, as a model protein, using anodic stripping voltammetry at
      electrodeposited bismuth film is presented. This biosensor involves the
      immobilization of the captured QDs conjugates which was dissolved with 1M HCl
      solution to release cadmium ions and metal components were quantified by anodic
      stripping voltammetry after a 3-min accumulation at -1.2V on bismuth-film
      electrode (BiFE) of the biotin, served as recognition element, onto the gold
      surface in connection with a cysteamine self-assembled monolayer. The
      modification procedure was characterized by electrochemical impedance
      spectroscopy and atomic force microscopy. We exploit QDs as labels for amplifying
      signal output and monitoring the extent of competition process between CdTe
      labeled neutravidin and the target neutravidin for the limited binding sites on
      biotin. As expected for the competitive mechanism, the recognition event thus
      yields distinct cadmium stripping voltammetric current peak, whose response
      decreases upon increasing the level of target neutravidin concentrations. Under
      optimal conditions, the voltammetric response is highly linear over the range of
      0.5-100 ngL(-1) neutravidin and the limit of detection is estimated to be 0.3
      ngL(-1) (5 nM). Unlike earlier two-step sandwich bioassays, the present protocol
      relies on a one-step competitive assay, which is more accurate and sensitive,
      showing great promise for rapid, simple and cost-effective analysis of protein.

PMID- 18722763
TI  - On-chip detection of protein glycosylation based on energy transfer between
      nanoparticles.
AB  - We describe a chip-based method to detect protein glycosylation based on the
      energy transfer between quantum dots (QDs) and gold nanoparticles (AuNPs). Our
      assay system relies on modulations in the energy transfer between the
      nanoparticles on a surface. The photoluminescence (PL) of lectin-coated QDs
      (energy donor) immobilized on a glass slide is quenched by carbohydrate-coated
      AuNPs (energy acceptor), and the presence of the glycoprotein causes the increase
      of the PL of QDs. As a proof-of-concept, Concanavalin A-coated QDs (ConA-QDs) and
      dextran-coated AuNPs (Dex-AuNPs) were used to detect the mannosylated proteins.
      As a result, the PL intensity of QDs was found to be linearly correlated with the
      concentration and the number of glycan moiety of the glycoprotein. We anticipated
      that our simple assay system will find applications for the analysis of
      glycoproteins with high selectivity and sensitivity in a high-throughput manner.

PMID- 18722764
TI  - An indirect competitive immunoassay for insulin autoantibodies based on surface
      plasmon resonance.
AB  - We have developed a sensitive and specific method based on surface plasmon
      resonance (SPR) for detection of insulin autoantibodies (IAA) in serum samples
      from individuals at high risk of developing type 1 diabetes (T1D). When measuring
      trace molecules in undiluted sera with label-free techniques like SPR, non
      specific adsorption of matrix proteins to the sensor surface is often a problem,
      since it causes a signal that masks the analyte response. The developed method is
      an indirect competitive immunoassay designed to overcome these problems. Today,
      IAA is mainly measured in radio immunoassays (RIAs), which are time consuming and
      require radioactively labeled antigen. With our SPR-based immunoassay the overall
      assay time is reduced by a factor of >100 (4 days to 50min), while sensitivity is
      maintained at a level comparable to that offered by RIA.

PMID- 18722765
TI  - The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer
      depends on the mismatch repair status.
AB  - AIMS: The aim of this study is to evaluate if mismatch repair (MMR) defective
      colorectal cancer has a different response to adjuvant 5-fluorouracil (5-FU)
      chemotherapy in a cohort of patients prospectively followed during 5 years.
      METHODS: The cohort included 754 surgically treated patients with colorectal
      cancer. MMR status was diagnosed by MLH1 and MSH2 immunohistochemistry and
      microsatellite instability analysis. Median follow-up was 49.2 months (range 1
      73). At inclusion, 505 patients were diagnosed as TNM II or III stage, analysis
      of the efficacy of adjuvant chemotherapy was made on this population. Adjuvant
      chemotherapy was applied to 248 patients (98.2% 5-FU based). RESULTS: MMR
      deficiency was found in 76 patients (10.1%). No differences were found in overall
      survival (log-rank p=0.3) or disease-free survival (log-rank p=0.3) regarding MMR
      status. Adjuvant chemotherapy improves survival in patients in the II or III
      stage, but this improvement is only evident in patients with MMR-competent
      tumours (log-rank p=0.00001). Survival of patients with MMR-defective tumours
      does not improve with adjuvant chemotherapy (log-rank p=0.7). A multivariate
      analysis showed an independent effect of the interaction between MMR status and
      adjuvant chemotherapy (Hazard ratio 2.04; 95% confidence interval: 1.42-2.93).
      CONCLUSION: In a cohort of colorectal cancer patients, those with MMR-deficient
      tumours seem not to benefit from 5-FU-based chemotherapy.

PMID- 18722766
TI  - Better patient awareness can lead to better treatment decisions.

PMID- 18722767
TI  - Lipid accumulation and CO2 utilization of Nannochloropsis oculata in response to
      CO2 aeration.
AB  - In order to produce microalgal lipids that can be transformed to biodiesel fuel,
      effects of concentration of CO(2) aeration on the biomass production and lipid
      accumulation of Nannochloropsis oculata in a semicontinuous culture were
      investigated in this study. Lipid content of N. oculata cells at different growth
      phases was also explored. The results showed that the lipid accumulation from
      logarithmic phase to stationary phase of N. oculata NCTU-3 was significantly
      increased from 30.8% to 50.4%. In the microalgal cultures aerated with 2%, 5%,
      10% and 15% CO(2), the maximal biomass and lipid productivity in the
      semicontinuous system were 0.480 and 0.142 g L(-1)d(-1) with 2% CO(2) aeration,
      respectively. Even the N. oculata NCTU-3 cultured in the semicontinuous system
      aerated with 15% CO(2), the biomass and lipid productivity could reach to 0.372
      and 0.084 g L(-1)d(-1), respectively. In the comparison of productive
      efficiencies, the semicontinuous system was operated with two culture approaches
      over 12d. The biomass and lipid productivity of N. oculata NCTU-3 were 0.497 and
      0.151 g L(-1)d(-1) in one-day replacement (half broth was replaced each day), and
      were 0.296 and 0.121 g L(-1)d(-1) in three-day replacement (three fifth broth was
      replaced every 3d), respectively. To optimize the condition for long-term biomass
      and lipid yield from N. oculata NCTU-3, this microalga was suggested to grow in
      the semicontinuous system aerated with 2% CO(2) and operated by one-day
      replacement.

PMID- 18722768
TI  - Hexahydro-pyrrolo- and hexahydro-1H-pyrido[1,2-b]pyridazin-2-ones as potent
      inhibitors of HCV NS5B polymerase.
AB  - Hexahydro-pyrrolo- and hexahydro-1H-pyrido[1,2-b]pyridazin-2-one analogs were
      discovered as a novel class of inhibitors of genotype 1 HCV NS5B polymerase.
      Among these, compound 4c displayed potent inhibitory activities in biochemical
      and replicon assays (IC(50) (1b) <10 nM; EC(50) (1b)=34 nM) as well as good
      stability towards human liver microsomes (HLM t(1/2) =59 min).

PMID- 18722769
TI  - Impacts of baicalein analogs with modification of the 6th position of A ring on
      the activity toward NF-kappaB-, AP-1-, or CREB-mediated transcription.
AB  - The water extract of Scutellariae baicalensis Georgi (S. baicalensis) has
      potential anti-tumor and anti-inflammatory activities. A major flavonoid isolated
      from S. baicalensis, baicalein, was also found to have anti-tumor and anti
      inflammatory activities. These biological activities could be due to their
      antioxidant action and/or effect on different signal transduction pathways. We
      investigated the effects of several baicalein analogs with a substitution of
      hydrogen of the hydroxyl group at the 6th position of A ring on three signal
      pathway mediated transcription (NF-kappaB, AP-1, and CREB) associated with
      inflammation and cancer growth. We found that the analogs with O-alkyl group of
      the different carbon chain length or O-benzyl activated NF-kappaB transcription
      without TNFalpha stimulation. Some of the analogs increased TNFalpha stimulated
      NF-kappaB transcription by two- to threefold. None of the analogs studied has
      major effect on AP-1 signal transduction with or without TPA stimulation. All of
      the analogs increased CREB transcription with forskolin stimulation up to
      twofold. However, they did not have a potent effect (less or about twofold
      activation) on intrinsic CREB signal transduction. The modification of baicalein
      at the 6th position of A ring was not correlated with change in these signal
      transduction pathways and cytotoxicity. Though, they are structural analogs, they
      are not functional analogs. Modification of baicalein at the 6th position could
      alter the specificity of action toward different cellular targets. Flavonoids
      could be chemophores in the development of drugs targeted at different signal
      transcriptional pathway.

PMID- 18722770
TI  - Discovery and optimization of (R)-prolinol-derived agonists of the Growth Hormone
      Secretagogue receptor (GHSR).
AB  - The discovery and optimization of a novel series of prolinol-derived GHSR
      agonists is described. This series emerged from a 11,520-member solid-phase
      library targeting the GPCR protein superfamily, and the rapid optimization of low
      micromolar hits into single-digit nanomolar leads can be attributed to the solid
      phase synthesis of matrix libraries, which revealed multiple non-additive
      structure-activity relationships. In addition, the separation of potent
      diastereomers highlighted the influence of the alpha-methyl stereochemistry of
      the phenoxyacetamide sidechain on GHSR activity.

PMID- 18722771
TI  - ortho-dihydroxyisoflavone derivatives from aged Doenjang (Korean fermented
      soypaste) and its radical scavenging activity.
AB  - One new ortho-dihydroxyisoflavone, 7,3',4'-trihydroxyisoflavone (2), and two
      known ortho-dihydroxyisoflavone derivatives were isolated from 5-year-old
      Doenjang (Korean fermented soypaste), and evaluated as potent antioxidant by
      comparing with other known isoflavones. 7,8,4'-Trihydroxyisoflavone (1), 7,3',4'
      trihydroxyisoflavone (2), and 6,7,4'-trihydroxyisoflavone (3) inhibited DPPH
      (Diphenyl-1-picryl hydrazyl) formation by 50% at a concentration of 21.5+/-0.2,
      28.7+/-0.4 and 32.6+/-0.6 (IC(50)), respectively, whereas three isoflavones
      showed weak DPPH radical scavenging activity. In xanthine oxidase (XO) system, in
      which both inhibition of xanthine oxidase and superoxide scavenging effect were
      measured in one assay. Compound 1 (IC(50)= 6.6+/-0.4 microM) and 2 (IC(50)=16.8+/
      1.2 microM) show significant inhibitory activity and greater effect than
      allopurinol. But, compound 3 and other isoflavones showed lower inhibition
      activity. This study shows that the position of hydroxyl substituent at the
      aromatic ring of isoflavone plays an important role in radical scavenging effect.

PMID- 18722773
TI  - Cognitive demands of postural control during continuous rotational perturbations
      of the support surface.
AB  - This research explored the effect of the level of balance challenge on the
      cognitive demands of dynamic balance. The postural task was maintaining balance
      while standing on a rotating platform that moved about the axis of the ankle
      joint in the pitch plane. Different frequencies and amplitudes of perturbation
      were employed to introduce different levels of balance challenge. The cognitive
      task was a silent word identification task. Results showed no significant
      difference in the participants' performance on the cognitive task in any of the
      dual-task conditions in comparison with their performance in the "cognitive only"
      condition. Furthermore, regardless of the level of balance challenge concurrent
      performance of the cognitive task did not affect the balance control strategies
      adopted by our participants. The lack of interference between the cognitive task
      and the present postural task might be due to the fact that the rotational
      perturbations induced very small Center of Mass (COM) displacements at all
      frequencies which were under the automatic control.

PMID- 18722772
TI  - Discovery of a novel class of PPARdelta partial agonists.
AB  - Anthranilic acid GW9371 was identified as a novel class of PPARdelta partial
      agonist through high-throughput screening. The design and synthesis of SAR
      analogues is described. GSK1115 and GSK7227 show potent partial agonism of the
      PPARdelta target genes CPT1a and PDK4 in skeletal muscle cells.

PMID- 18722775
TI  - Optimizing patellofemoral arthroplasty.
AB  - Patellofemoral arthroplasty (PFA) has been an option for patients with
      symptomatic patellofemoral osteoarthritis since the 1950's. Many of the early
      failures resulted from a combination of implant design and surgeon technique. The
      goal of this overview is not to review the history of PFA, but rather to explore
      options for surgeons to optimize long-term outcomes and improve patient knee
      function, while highlighting the differing techniques required in PFA with those
      routinely adopted in total knee arthroplasty (TKA).

PMID- 18722776
TI  - Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: potent CYP26 inhibitors and
      enhancers of all-trans retinoic acid activity in neuroblastoma cells.
AB  - The synthesis and potent inhibitory activity of novel 4-[(imidazol-1-yl and
      triazol-1-yl)(phenyl)methyl]aryl-and heteroaryl amines versus a MCF-7 CYP26A1
      cell assay is described. Biaryl imidazole ([4-(imidazol-1-yl-phenyl-methyl)
      phenyl]-naphthalen-2-yl-amine (8), IC(50)=0.5 microM; [4-(imidazol-1-yl-phenyl
      methyl)-phenyl]-indan-5-yl-amine (9), IC(50)=1.0 microM) and heteroaryl imidazole
      derivatives ((1H-benzoimidazol-2-yl)-{4-[(5H-imidazol-1-yl)-phenyl-methyl]
      phenyl}-amine (15), IC(50)=2.5 microM; benzooxazol-2-yl-{4-[(5H-imidazol-1-yl)
      phenyl-methyl]-phenyl}-amine (16), IC(50)=0.9 microM; benzothiazol-2-yl-{4-[(5H
      imidazol-1-yl)-phenyl-methyl]-phenyl}-amine (17), IC(50)=1.5 microM) were the
      most potent CYP26 inhibitors. Using a CYP26A1 homology model differences in
      activity were investigated. Incubation of SH-SY5Y human neuroblastoma cells with
      the imidazole aryl derivative 8, and the imidazole heteroaryl derivatives 16 and
      17 potentiated the atRA-induced expression of CYP26B1. These data suggest that
      further structure-function studies leading to clinical development are warranted.

PMID- 18722777
TI  - Derivatives of 1,4-bis(3-hydroxycarbonyl-4-hydroxyl)styrylbenzene as PTP1B
      inhibitors with hypoglycemic activity.
AB  - Disalicylic acid derivatives with stilbene and bis-styrylbenzene skeleton were
      synthesized as PTP1B inhibitors. The most potent in this series exhibited a
      submicromolar IC(50) value. One of the compounds 7b was tested in an animal model
      for its efficacy as an anti-diabetic or an anti-obesity agent. In feeding
      compound 7b to diet-induced obese mice, no significant differences in weight gain
      and food consumption were observed between the drug-treated and the obese control
      mice. However, 7b significantly lowered the fasting glucose level and improved
      the glucose tolerance in the obesity-induced diabetic mice.

PMID- 18722778
TI  - Tetrahydropyridine-4-carboxamides as novel, potent transient receptor potential
      vanilloid 1 (TRPV1) antagonists.
AB  - A series of 1,2,3,6-tetrahydropyridyl-4-carboxamides, exemplified by 6, have been
      synthesized and evaluated for in vitro TRPV1 antagonist activity, and in vivo
      analgesic activity in animal pain models. The tetrahydropyridine 6 is a novel
      TRPV1 receptor antagonist that potently inhibits receptor-mediated Ca2+ influx in
      vitro induced by several agonists, including capsaicin, N-arachidonoyldopamine
      (NADA), and low pH. This compound penetrates the CNS and shows potent anti
      nociceptive effects in a broad range of animal pain models upon oral dosing due
      in part to its ability to antagonize both central and peripheral TRPV1 receptors.
      The SAR leading to the discovery of 6 is presented in this report.

PMID- 18722779
TI  - Monochromated, spatially resolved electron energy-loss spectroscopic measurements
      of gold nanoparticles in the plasmon range.
AB  - Gold nanoparticles show optical properties different from bulk material due to
      resonance phenomena which depend on local structure and geometry. Electron energy
      loss spectrometry (EELS) in scanning transmission electron microscopy (STEM)
      allows the spatially resolved measurement of these properties at a resolution of
      few nanometers. In this work, the first monochromated measurements of gold
      nanoparticles (spheres, rods and triangles) are presented. Due to the improved
      energy resolution of about 0.2 eV, surface plasmon excitations at energies below
      1 eV could be accurately measured from raw experimental data.

PMID- 18722780
TI  - Cytochemical characterization of Triatoma infestans and Panstrongylus megistus
      salivary gland cells (Hemiptera, Reduviidae, Triatominae).
AB  - The Triatominae subfamily has medical sanitary importance, since these insects
      are vectors of Trypanosoma cruzi, etiologic agent of Chagas Disease, and
      Trypanosoma rangeli, which develops in the salivary glands and it is frequently
      found in mixed infections with T. cruzi. Triatomines of Triatoma and
      Panstrongylus genera possess a salivary gland complex composed of a pair with
      three well differentiated units: the anterior (D1), median (D2) and posterior
      (D3). Saliva is secreted during blood meal and antagonizes hemostatic,
      inflammatory and immunological systems imposed by the host, which facilitate the
      hematophagy. In order to identify nuclear structures, we studied interphase
      nuclei of salivary gland cells of adult insects, males and females, of Triatoma
      infestans and Panstrongylus megistus. The glands were removed from insects, fixed
      in acetic acid (45%) and lactic acid (50%), squashed and submitted to different
      cytochemical methods: lacto-acetic orcein, silver ion impregnation, Feulgen
      reaction, Toluidine Blue, Variant method of critical electrolyte concentration
      and C-banding. The preparations were examined with a Zeiss Jenaval
      photomicroscope and photographed. The results evidenced predominance of
      binucleated cells in D1 and D2 glands and mononucleated ones in D3. In all
      salivary glands were observed bulky and polyploid nucleus, a clear association
      between nucleolar and heterochromatic corpuscles, cytoplasmatic metachromasy and
      many pre-secretion vesicles in cytoplasm. Such characteristics were associated
      with intense synthesis activity to produce the saliva. Species were mainly
      differentiated by a larger heterochromatic corpuscle observed only in T.
      infestans (called as chromocenter), while P. megistus showed a predominance of
      euchromatin, with some heterochromatic corpuscles just in males. Females of both
      species showed a smaller quantity of heterochromatin, which could be related to
      the high metabolism because of the oviposition.

PMID- 18722781
TI  - Sivelestat attenuates postoperative pulmonary dysfunction after total arch
      replacement under deep hypothermia.
AB  - BACKGROUND: Total arch replacement necessitating deep hypothermia with
      circulatory arrest has a greater effect on pulmonary function than other cardiac
      surgery using cardiopulmonary bypass (CPB). Since April 2004, 100mg of sivelestat
      sodium hydrate was administrated by bolus injection into pulp circuit at the
      initiation of CPB in every case performed total arch replacement. We investigated
      the hypothesis that prophylactic use of the drug attenuates post-pump pulmonary
      dysfunction. METHODS: A retrospective analysis of 120 consecutive patients who
      underwent total arch replacement from August 2001 to December 2006 was conducted.
      Patients were divided into two groups according to the date of surgery, April
      2004, when we started sivelestat administration. Group A (n=60), operated after
      April 2004, was administrated sivelestat at the initiation of CPB. Group B
      (n=60), before April 2004, was not administrated. Time courses of hemodynamic
      variables were evaluated until 24h after surgery and those of respiratory
      variables and inflammatory markers until 48 h after surgery. RESULTS: There were
      no significant differences in patient age, sex, prevalence of chronic obstructive
      lung disease, preoperative lung function, time of operation and CPB, minimum
      temperature, and aprotinin usage. Hospital mortality occurred in two patients in
      the group B (3.3%) and no patient in group A (0%). Postoperative hemodynamic
      variables were not different between the two groups. Respiratory index,
      oxygenation index were significantly better in patients pretreated with
      sivelestat (respiratory index; p<0.001, oxygenation index; p<0.001,
      respectively). CRP was significantly lower in patients pretreated with sivelestat
      (p=0.022). Except for patients who required tracheostomy or re-exploration for
      bleeding, patients pretreated with sivelestat were extubated significantly
      shorter (group A: 12.6+/-10.8h, group B: 25.5+/-12.9h, p=0.033). No patient with
      postoperative respiratory failure requiring tracheostomy was noted in sivelestat
      group. CONCLUSION: Prophylactic administration of sivelestat at the initiation of
      CPB results in better postoperative pulmonary function, leading to earlier
      extubation time. Our study suggests that sivelestat was effective in facilitating
      postoperative respiratory management in total arch replacement.

PMID- 18722783
TI  - Post-sternotomy percutaneous tracheostomy and risky multivariable analyses.

PMID- 18722784
TI  - Irinotecan in the treatment of elderly patients with advanced colorectal cancer.
AB  - Irinotecan is an active drug in the first and subsequent lines of chemotherapy
      for patients with advanced colorectal cancer. Frequently, the elderly patients
      are excluded from receiving irinotecan alone or in combination, and on many
      occasions these patients receive an initial reduced dose of this drug. This
      revision has been focused in the role of irinotecan in elderly patients. MATERIAL
      AND METHODS: Data from pharmacokinetic studies, comparative analysis of
      prospective trials according to age and prospective studies with irinotecan alone
      or irinotecan-combinations in the elderly have been revised and put into context.
      RESULTS: Either pharmacokinetic and clinical data suggest that fit elderly
      patients may tolerate irinotecan as well as the younger population. Response rate
      and survival achieved in elderly patients with irinotecan combinations seem to be
      equivalent to that obtained in younger patients. CONCLUSION: Elderly patients
      with advanced colorectal cancer should be carefully evaluated in order to be
      classified as fit or not fit through a comprehensive geriatric assessment. For
      the group of fit elderly patients, irinotecan may be used as in the younger
      population.

PMID- 18722785
TI  - Women and lung cancer: clinical and molecular profiling as a determinate for
      treatment decisions: a literature review.
AB  - In the past decade the incidence of lung cancer among women has risen, whereas
      among men it has slightly declined. Important differences in lung cancer have
      been demonstrated between men and women, although many areas still remain
      controversial. Some biologic differences may justify the increase in response of
      women to therapy for lung cancer and can partially explain the improved survival
      of women compared with men. We extensively reviewed the published scientific
      literature on this topic in order to investigate the clinical and genetic
      profiling underlying lung cancer in women and to use this information as a tool
      for medical therapy.

PMID- 18722786
TI  - Regulatory T cells in health and disease.
AB  - Regulatory T (Treg) cells have emerged as a central control point in the
      modulation of various immune responses, including autoimmune responses and
      immunity to transplants, allergens, tumors, and infectious microbes. The immune
      system has evolved complex processes to ensure tolerance to autoantigens while
      preserving the potential to mount and maintain life-long humoral and cellular
      immune responses against invading pathogens. In this review, we summarize
      research showing that naturally occurring (nTreg) and induced Treg (iTreg) cell
      subsets, and in particular CD4+Foxp3+ Treg cells, are critical in the control of
      immune responses in rodents and humans. We also discuss the cellular and
      molecular factors that affect CD4+Foxp3+ Treg cell development, homeostasis, and
      function and consequential immunity to self and non-self antigens. Recent studies
      have shed light in our understanding of the development of novel methods of
      autoimmune disease prevention and treatment via enhancing and re-establishing
      Treg-mediated dominant control over self-reactive T cells in animal models and
      humans.

PMID- 18722787
TI  - Fat diet and alcohol-induced steatohepatitis after LPS challenge in mice: role of
      bioactive TNF and Th1 type cytokines.
AB  - Obesity with insulin resistance and alcohol are the most frequent causes of
      steatohepatitis. This work investigates the contribution of bioactive TNF and Th1
      type cytokines in a mouse model of steatohepatitis induced by FAT alone or
      FAT+EtOH and endotoxin. The extent of liver injury and cytokine activation
      induced by endotoxin in chronic FAT-fed mice, FAT+EtOH-fed mice, or mice fed
      standard chow were analyzed. Endotoxin administration to either FAT-fed or
      FAT+EtOH-fed mice increased serum ALT and AST compared to standard chow mice.
      Immunoreactive TNF was strongly activated by LPS in FAT-fed and FAT+EtOH-fed mice
      which presented the highest levels, but low levels were found in standard chow
      mice. In contrast, bioactive TNF was only present in serum of FAT-fed and in
      particular the highest levels were found in FAT+EtOH-fed mice. Moreover, soluble
      TNFR2 but not TNFR1 was found in lower amounts in serum of FAT+EtOH-fed mice
      compared to FAT-fed mice. Steatohepatitis was associated with increased IL-6, IFN
      gamma, and iNOS mRNA and proteins. Data show that a moderately FAT diet and low
      dose EtOH concur to generate steatohepatitis and TNF liver expression after LPS.
      In this model, changes in the regulation of TNF are associated with increased
      expression of IL-6, IFN-gamma, and iNOS.

PMID- 18722788
TI  - Cell markers and determinants in fish immunology.
AB  - Despite the impressive increase in the cloning and expression of genes encoding
      fish immunoregulatory molecules, the knowledge on "in vivo" and "in vitro"
      functional immunology of the corresponding peptide products is still at an
      initial stage. This is partly due to the lacking of specific markers for
      immunoregulatory peptides, that represent an indispensible tool to dissect immune
      reactions and to trace the fate of cellular events downstream of the activation.
      In this review we summarise the available information on functional immune
      activities of some teleost species and discuss the obtained data in an
      evolutionary and applied context.

PMID- 18722789
TI  - A history of fish immunology and vaccination I. The early days.
AB  - This historic review describes the people that were involved in studying some
      aspect of fish immunology and vaccination from as early as 1854. Between 1850 and
      1940, most scientists were looking at fish from the angle of comparative anatomy,
      embryology, physiology, taxonomy and fish diseases. Most publications from this
      early period are describing the morphology of blood cells and hemopoietic or
      lymphoid organs. The first publications on specific immune responses and
      vaccination of fish were found in the period 1935-1938. However, the immune
      mechanisms behind protective immunization were largely unknown in those days. In
      the period after 1940, the first researchers can be found devoting their whole
      career to fish immunology. This paper has been organized largely by individuals
      and not so much by accomplishments. It is not the intent of this review to
      evaluate the scientific merit of the work discussed, but to provide the reader
      with information that was - at least in part - lost to the scientific community.
      Publications from before 1940 or in languages other than English (e.g. Russian)
      are usually not found by today's database searches on the Internet.

PMID- 18722790
TI  - Living off a fish: a trade-off between parasites and the immune system.
AB  - Research in fish immune system and parasite invasion mechanisms has advanced the
      knowledge of the mechanisms whereby parasites evade or cope with fish immune
      response. The main mechanisms of immune evasion employed by fish parasites are
      reviewed and considered under ten headings. 1) Parasite isolation: parasites
      develop in immuno-privileged host tissues, such as brain, gonads, or eyes, where
      host barriers prevent or limit the immune response. 2) Host isolation: the host
      cellular immune response isolates and encapsulates the parasites in a dormant
      stage without killing them. 3) Intracellular disguise: typical of intracellular
      microsporidians, coccidians and some myxosporeans. 4) Parasite migration,
      behavioural and environmental strategies: parasites migrate to host sites the
      immune response has not yet reached or where it is not strong enough to kill
      them, or they accommodate their life cycles to the season or the age in which the
      host immune system is down-regulated. 5) Antigen-based strategies such as mimicry
      or masking, variation and sharing of parasite antigens. 6) Anti-immune
      mechanisms: these allow parasites to resist innate humoral factors, to neutralize
      host antibodies or to scavenge reactive oxygen species within macrophages. 7)
      Immunodepression: parasites either suppress the fish immune systems by reducing
      the proliferative capacity of lymphocytes or the phagocytic activity of
      macrophages, or they induce apoptosis of host leucocytes. 8) Immunomodulation:
      parasites secrete or excrete substances which modulate the secretion of host
      immune factors, such as cytokines, to their own benefit. 9) Fast development:
      parasites proliferate faster than the ability of the host to mount a defence
      response. 10) Exploitation of the host immune reaction. Knowledge of the evasion
      strategies adopted by parasites will help us to understand host-parasite
      interactions and may therefore help in the discovery of novel immunotherapeutic
      agents or targeted vaccines, and permit the selection of host-resistant strains.

PMID- 18722791
TI  - Transcriptional up-regulation of disk abalone selenium dependent glutathione
      peroxidase by H(2)O(2) oxidative stress and Vibrio alginolyticus bacterial
      infection.
AB  - Selenium dependent glutathione peroxidase (Se-GPx) belongs to the family of
      selenoprotein, which acts mainly as an antioxidant in the cellular defence
      system. We have identified Se-GPx full length cDNA from disk abalone (Haliotis
      discus discus) designated as AbSe-GPx. It has a characteristic codon at
      (223)TGA(225) that corresponds to selenocysteine (Sec) amino acid as U(75). The
      full length cDNA consists of 675 bp, an open reading frame encoding 225 amino
      acids. Sequence characterization revealed that AbSe-GPx contains a characteristic
      GPx signature motif 2 ((97)LGFPCNQF(104)), an active site motif
      ((183)WNFEKF(188)) and essential residues for the enzymatic function.
      Additionally, the eukaryotic selenocysteine insertion sequence (SECIS) is
      conserved in the 3' UTR. The AbSe-GPx amino acid sequence exhibited the highest
      level of identity (46%) with insect (Ixodes scapularis) GPx, and shares 41% with
      bivalve (Unio tumidus) Se-GPx. The RT-PCR analysis revealed that AbSe-GPx mRNA
      was expressed constitutively in gill, mantle, gonad, abductor muscle, digestive
      tract, and hemocytes in a tissue specific manner. AbSe-GPx mRNA expression was
      significantly up-regulated in gill and digestive tract tissues after H(2)O(2)
      injection and Vibrio alginolyticus infection. However, AbSe-GPx expression was
      not up-regulated after Aroclor 1,254 injection. These results indicate that AbSe
      GPx mRNA is expressed at a basal level in abalone tissues, which can be up
      regulated transcriptionally by H(2)O(2) oxidative stress and Vibrio alginolyticus
      infection. Therefore, AbSe-GPx may be involved in a protective role against
      H(2)O(2) oxidative stress and immune defence against bacterial infection.

PMID- 18722792
TI  - Is my body the sum of online and offline body-representations?

PMID- 18722793
TI  - Care in people 60 years of age and over with chronic or recently diagnosed
      epilepsy: a note review in United Kingdom general practice.
AB  - AIM: To ascertain present United Kingdom (UK) management processes for epilepsy
      in older people. METHOD: This was a general practice notes review of people being
      treated for epilepsy 60 years and over. RESULTS: The cohort of 110 was from six
      practices. Seizure frequency in older people with epilepsy appears lower than in
      general; 75% are seizure free. This compares with 40-60% of people in other
      general practice note reviews and audits, where age is not a factor. Out of the
      people still having seizures over half have less than one seizure per month.
      Monotherapy rates are similar to the population in general. Nobody was taking
      more than two AEDs. There is evidence of new AED use, especially lamotrigine; it
      is the most commonly prescribed AED in those diagnosed in later life.
      Geriatricians appear to receive virtually no referrals for the diagnosis of
      epilepsy. General physicians, psychiatrists and neurologists receive many more.
      Geriatricians and general physicians appear never to follow up older people with
      epilepsy; GPs following up 91%, and neurologists and specialist nurses 9%.
      CONCLUSIONS: Seizure frequency in older people with epilepsy is generally low.
      Geriatricians appear to receive virtually no referrals for the diagnosis or
      management of epilepsy in older people. Follow up is mainly undertaken by GPs.
      Although lamotrigine has a difficult dosing schedule, which may be confusing for
      some older people, its use is high perhaps reflecting recent guidelines and
      evidence. These results may be peculiar to the geographical area used, so other
      work is needed to confirm or refute these findings.

PMID- 18722795
TI  - "Is robotic surgery right for vascular procedures? Report of 100 aortoiliac
      cases" by Petr Stadler, et al.

PMID- 18722794
TI  - Endovascular therapy of a symptomatic mobile thrombus of the thoracic aorta.
AB  - INTRODUCTION: The therapeutic strategies of a mobile luminal thrombus of the
      descending thoracic aorta with peripheral arterial embolization remain a matter
      of debate. REPORT: We report the case of recurrent peripheral arterial embolism
      caused by a mobile thrombus of the descending aorta, which was successfully
      treated by implanting an endovascular stent graft. DISCUSSION: Our case
      demonstrates, that endovascular stent graft placement is feasible and can be
      performed as an effective and minimally invasive treatment option for mobile
      thoracic aortic thrombi.

PMID- 18722796
TI  - Sensitivity losses and line shape modifications due to molecular diffusion in
      continuous encoding ultrafast 2D NMR experiments.
AB  - Recent ultrafast techniques make it possible to obtain multidimensional (nD) NMR
      spectra in a single scan. These ultrafast methods rely on a spatial encoding
      process based on radiofrequency (RF) pulses applied simultaneously with magnetic
      field gradients. Numerous approaches have been proposed in the past few years to
      perform this excitation process, most of them relying on a continuous excitation
      of the spins throughout the whole sample. However, the resolution and sensitivity
      of ultrafast nD spectra are often reduced by molecular diffusion effects due to
      the presence of gradients during the excitation process. In particular,
      increasing the excitation period is necessary to improve the resolution in the
      ultrafast dimension, but it leads to high sensitivity losses due to diffusion. In
      order to understand better and to limit molecular diffusion effects, a detailed
      theoretical and experimental study of the various continuous ultrafast excitation
      processes is carried out in the present study. New numerical simulations of
      ultrafast echo line shapes are presented and compared to experimental data. The
      evolution of the signal intensity with the excitation process duration is also
      simulated and compared to experimental intensity losses. The different excitation
      schemes are compared in order to determine the best excitation conditions to
      perform 2D ultrafast experiments with optimum resolution and sensitivity. The
      experimental and theoretical results put in evidence the efficiency of the multi
      echo scheme.

PMID- 18722797
TI  - Technical and biochemical factors affecting cerebrospinal fluid 5-MTHF, biopterin
      and neopterin concentrations.
AB  - BACKGROUND: The diagnosis of pediatric neurologic disorders with a deficiency in
      the biosynthesis of either the neurotransmitters serotonin and dopamine, or the
      co-factor tetrahydrobiopterin or a cerebral 5-methyltetrahydrofolate (5-MTHF)
      deficiency, strongly relies on a robust analysis of neurotransmitter metabolites,
      pterins and 5-MTHF in the cerebrospinal fluid (CSF). The aim of this study was to
      investigate which technical and biochemical factors affect the CSF concentration
      of 5-MTHF, neopterin and biopterin in a pediatric population. METHODS: We studied
      effects of the ventriculo-spinal gradient, total protein concentration,
      pretreatment with ascorbic acid (in case of 5-MTHF analysis), pretreatment of CSF
      with trichloro acetic acid (TCA)/dithiotreitol (DTE) and oxidation with either
      iodine or manganese oxide (in case of pterin analysis), storage time and age of
      the patients. We included CSF samples from children until the age of 18 years and
      analysed 5-MTHF, neopterin, biopterin, homovanillic acid (HVA), 5-hydroxy
      indoleacetic acid (5-HIAA) and total protein. RESULTS: The major findings of our
      study are: (1) CSF 5-MTHF, neopterin and biopterin concentrations are not
      affected by the ventriculo-spinal gradient; (2) pretreatment of CSF with ascorbic
      acid has negligible effects on 5-MTHF concentrations; (3) pretreatment of CSF
      with TCA/DTE and oxidation with iodine results in the most accurate determination
      of neopterin and biopterin; (4) when adjusted for age and total protein, CSF 5
      MTHF correlated with 5-HIAA, but not with HVA; (5) the reference value of 5-MTHF
      in CSF in childhood is age-dependent (r=-0.634; p0.001); (6) we did not observe
      an age-dependency for neopterin and biopterin in CSF. CONCLUSION: 5-MTHF,
      neopterin and biopterin can be analysed in any volume of CSF that is collected.
      For correct analysis of pterins, CSF will have to be pretreated to stabilize the
      concentrations and stored properly, whereas such pretreatment is not necessary
      for 5-MTHF.

PMID- 18722798
TI  - Vitamin D inadequacy in French osteoporotic and osteopenic women.
AB  - OBJECTIVE: Studies have shown that low serum vitamin D levels are associated with
      secondary hyperparathyroidism, which decreases bone strength and increases
      fracture risk, most notably after 50 years of age. The objective of this study
      was to evaluate the vitamin D status of postmenopausal women in France. METHODS:
      We conducted a cross-sectional observational study of 1292 menopausal women with
      osteoporosis or osteopenia. The age range was 52-94 years. Serum 25-OH-vitamin D
      was assayed in each patient. Based on data in the literature, we used four 25-OH
      D cutoffs to define vitamin D deficiency: 30, 50, 75, and 80 nmol/L (<12, <20,
      <30, and <32 ng/ml). RESULTS: Mean serum 25-OH-D was 51.5+/-26.1 nmol/L (about
      20.6+/-10.4 ng/ml). In the 343 (26.5%) patients taking supplemental vitamin D
      with or without supplemental calcium, the mean serum 25-OH-D level was
      significantly higher than in the other patients (65.0+/-26.0 ng/ml vs. 46.6+/
      18.6 ng/ml; P<0.001). In the subgroup not taking vitamin D supplements, the
      prevalence of vitamin D deficiency was 27.3%, 54.1%, 89.9%, and 93.2% with the
      30, 50, 75, and 80 nmol/L cutoffs, respectively. The mean 25-OH-D level varied
      across seasons (P<0.001), with the highest value being obtained in summer (53.4+/
      18.7 nmol/L; about 21.3+/-7.5 ng/ml). CONCLUSION: Vitamin D deficiency is common
      among postmenopausal women with osteoporosis or osteopenia in France.

PMID- 18722799
TI  - Synthesis and characterization of stable Co and Cd doped nickel hydroxide
      nanoparticles for electrochemical applications.
AB  - The present paper describes the physical-chemical characterization and
      electrochemical behavior of a new nanomaterial formed by the addition of cadmium
      and cobalt atoms into the structure of nickel hydroxide nanoparticles, these ones
      synthesized by an easy sonochemical method. Particles of about 5 nm diameter were
      obtained and characterized by high resolution transmission electron microscopy
      (HRTEM), X-ray diffraction and Raman spectroscopy. Different nickel hydroxide
      nanoparticles were immobilized onto transparent conducting substrates by using
      electrostatic layer-by-layer providing thin films at the nanoscale and the
      electrochemical behavior was investigated. The formation of a mixed hydroxide was
      corroborated by observation of very interesting properties as redox potential
      shifting to less positive potentials and high stability when submitted to long
      electrochemical cycling or high times of ultrasonic synthesis, suggesting
      practical applications.

PMID- 18722800
TI  - Sonochemical decomposition of organic acids in aqueous solution: understanding of
      molecular behavior during cavitation by the analysis of a heterogeneous reaction
      kinetics model.
AB  - The sonochemical decomposition of a low concentration of butyric acid was
      performed in an aqueous solution by use of 200 kHz ultrasound to discuss the
      reaction kinetics and molecular behavior during cavitation. Taking into account a
      Langmuir-type adsorption model, we propose a heterogeneous reaction kinetics
      model, which is based on the local reaction zone at the interface region of the
      cavitation bubbles, where the adsorption and desorption of butyric acid molecules
      from the bulk solution occur during bubble oscillation and then the existing
      molecules inside the local reaction zone are finally decomposed. To confirm our
      proposed kinetics model, the rates of decomposition were investigated as a
      function of the initial concentration of butyric acids in the different pH
      solutions. It was confirmed that our model could be reasonably applied to explain
      the obtained results and the pseudo rate constant (k) and the equilibrium
      constant (K) were able to be calculated: k is 8.0 microM min(-1) (pH 2) and 3.5
      microM min(-1) (pH 10), and K is 5.7 x 10(-3) microM(-1) (pH 2) and 8.0 x 10(-3)
      microM(-1) (pH 10), respectively. By the analysis of the obtained K values, it
      was clear that the ionized organic acid molecules are relatively difficult to
      accumulate at the reaction zone, because of their lower hydrophobicity compared
      with that of the neutral ones. The results obtained in the sonochemical
      decomposition of benzoic acid were also able to be analyzed with the proposed
      kinetics model. In addition, we proposed an opinion toward the interpretation of
      a Langmuir-type adsorption model which has often been applied to explain
      heterogeneous reaction systems.

PMID- 18722801
TI  - Compound heterozygosity in DJ-1 gene non-coding portion related to parkinsonism.
AB  - In this study we analysed the DJ-1 gene in 40 sporadic patients with early onset
      Parkinson's disease and 100 appropriate controls, originated from southern Italy.
      We identified a single patient with age at onset of 38 years carrying two
      previously undescribed heterozygous mutations, both located in non-coding
      regions. The first mutation was a nucleotide change in the promoter region of the
      gene (g.159C>G) and the second one was an insertion in the intron 4 splice site
      (IVS4+3insA). In the same patient, genomic rearrangements were excluded. No DJ-1
      mutations were found in the remaining parkinsonian patients. Our results support
      the growing importance of mutations in non-coding portion of human genome, and
      confirm that alterations in DJ-1 are a cause, even if rare, of early-onset
      Parkinson's disease.

PMID- 18722803
TI  - Membrane-bound transcription factors in plants.
AB  - The ability to activate dormant transcription factors is an important molecular
      feature of the transcriptional regulatory networks that govern diverse cellular
      functions. An intriguing example is the controlled proteolytic activation of
      membrane-bound transcription factors (MTFs). Most MTFs are activated either by
      intramembrane proteases or by the ubiquitin-proteasome pathway. Recent studies
      have shown that several members of the bZIP and NAC families in Arabidopsis are
      membrane-associated and are activated by membrane-associated proteases during
      stress responses in the endoplasmic reticulum and when the plants experience
      environmental stresses. A genome-scale analysis shows that over 10% of all
      transcription factors are membrane bound, indicating that activation of MTFs
      occurs at the genomic level, allowing transcription to be regulated rapidly under
      stressful conditions.

PMID- 18722802
TI  - Dopamine beta-hydroxylase -1021C>T association and Parkinson's disease.
AB  - A single nucleotide polymorphism in the promoter region of the dopamine beta
      hydroxylase gene (DBH -1021C>T; rs1611115) is reported to regulate plasma enzyme
      activity levels. This variant has also been the focus of two large association
      studies in Parkinson's disease yielding conflicting results. We examined this
      association in four Caucasian patient-control series (n=2696). A modest
      protective association was observed in the Norwegian series (OR=0.81, p=0.03;
      n=1676), however, the effect was in the opposite direction in the Polish series
      (OR=2.01, p=0.01; n=224). No association was observed for DBH -1021C>T with
      disease susceptibility in the US and Irish series, or combining all four series
      (OR=0.91, p=0.16, n=2696). We observed a modest association between DBH -1021C>T
      and AAO in the combined series (p=0.01). Taken together, these findings indicate
      that DBH -1021C>T does not play a major role in the pathogenesis of Parkinson's
      disease.

PMID- 18722804
TI  - Time to pump iron: iron-deficiency-signaling mechanisms of higher plants.
AB  - Iron is an essential nutrient for plants, yet it often limits plant growth. On
      the contrary, overaccumulation of iron within plant cells leads to oxidative
      stress. As a consequence, iron-uptake systems are carefully regulated to ensure
      that iron homeostasis is maintained. In response to iron limitation, plants
      induce expression of sets of activities that function at the root-soil interface
      to solubilize iron and subsequently transfer it across the plasma membrane of
      root cells. Recent advances have revealed key players in the signaling pathways
      that function to induce these iron-uptake responses. Transcription factors
      belonging to the basic helix-loop-helix, ABI3/VP1(B3), and NAC families appear to
      function either directly or indirectly in the upregulation of iron deficiency
      responses.

PMID- 18722805
TI  - Infrared studies of lead(II) halide-1,10-phenanthroline photosensitive materials.
AB  - Infrared spectroscopic studies of 1:1 and 1:2 complexes of lead(II) bromide and
      lead(II) iodide with 1,10-phenanthroline were reported. Vibrational assignments
      are made by comparison to reported spectra of the uncomplexed 1,10-phenanthroline
      molecule. Small shifts of the ligand vibrational bands are characteristic of the
      complexes.

PMID- 18722806
TI  - Structural elucidation, optical, magnetic and nonlinear optical properties of
      oxystyryl dyes.
AB  - Structure, magnetic and optical properties of tetraphenylborate salts of 2,5-[1
      methyl-4-[2-(4-hydroxyphenyl)ethenyl]piridinium]-propane and butane are performed
      in gas and condense phase by means of solution and solid-state conventional and
      linear-polarized IR-spectroscopy of oriented colloids in nematic liquid crystal
      suspension, UV-vis and fluorescence methods, HPLC tandem ESI mess spectrometry
      (MS/MS), (1)H, (13)C and (1)H-(1)H COSY NMR, TGV and DSC methods. Quantum
      chemical DFT calculations are used for performing of the structures, optical and
      nonlinear optical properties of the studied compounds.

PMID- 18722807
TI  - Preparation and spectral investigation of inclusion complex of caffeic acid with
      hydroxypropyl-beta-cyclodextrin.
AB  - The inclusion complexation behavior of caffeic acid (CA) with hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) was studied by UV-vis, fluorescence spectroscopy and
      nuclear magnetic resonance spectroscopy (NMR). Experimental conditions including
      the concentration of HP-beta-CD and media acidity were investigated in detail.
      The result suggested HP-beta-CD was more suitable for including CA in acidity
      solution. The binding contants (K) of the inclusion complexes were determined by
      linear regression analysis and the inclusion ratio was found to be 1:1. The water
      solubility of CA was increased by inclusion with HP-beta-CD according to the
      phase-solubility diagram. The spatial configuration of complex has been proposed
      based on (1)H NMR and two-dimensional (2D) NMR, the result suggested that CA was
      entrapped inside the hydrophobic core of HP-beta-CD with the lipophilic aromatic
      ring and the portion of ethylene.

PMID- 18722808
TI  - DFT based computational study on the excited state intramolecular proton transfer
      processes in o-hydroxybenzaldehyde.
AB  - Potential energy (PE) curves for the intramolecular proton transfer in the ground
      (GSIPT) and excited (ESIPT) states of o-hydroxybenzaldehyde (OHBA) were studied
      using DFT-B3LYP/6-31G(d) and TD-DFT-B3LYP/6-31G(d) level of theory, respectively.
      Our calculations suggest the non-viability of ground state intramolecular proton
      transfer in this compound. Excited states PE calculations support the ESIPT
      process in OHBA. The contour PE diagram and the variation of oscillator strength
      along the proton transfer co-ordinate support the dual emission in OHBA. Our
      calculations also support the experimental observations of Nagaoka et al. [S.
      Nagaoka, U. Nagashima, N. Ohta, M. Fujita, T. Takemura, J. Phys. Chem. 92 (1988)
      166], i.e. normal emission of the title compound comes from S(2) state and the
      red-shifted proton transfer band appears from the S(1) state. ESIPT process has
      also been explained in terms of HOMO and LUMO electron density of the enol and
      keto tautomer of OHBA and from the potential energy surfaces.

PMID- 18722809
TI  - Minerals from Macedonia XXIII. Spectroscopic and structural characterization of
      schorl and beryl cyclosilicates.
AB  - IR and Raman spectroscopy study on two collected cyclosilicate species: schorl
      (from tourmaline group), Na(Fe,Mg)(3)Al(6)(BO(3))(3)Si(6)O(18)(OH,F)(4) and beryl
      (Be,Mg,Fe)(3)Al(2)Si(6)O(18) were carried out. Although beryl is nominally
      anhydrous mineral, vibrational results strongly indicate that H(2)O molecules
      exist in the structural channels. The number of vibrational bands and their
      frequencies revealed the presence of H(2)O type II, in which C(2) symmetry axis
      of the water molecule is parallel to the structural channel (and to the c-axis of
      beryl). On the other hand, it was found that observed bands in the IR and Raman
      OH stretching region of the other tourmaline varieties appear as a result of the
      cation combinations involving dominant presence of Mg and Fe cations in the Y
      structural sites. The strong indication derived from the vibrational
      spectroscopic results that the studied mineral represents a schorl variety,
      coincide very well with the results obtained by powder X-ray diffraction and X
      ray microprobe analysis. Both minerals show IR spectral similarities in the
      region below 1500 cm(-1), whereas the resemblance between the Raman spectra (1500
      100 cm(-1)) is less expressed confirming that these spectra are more sensitive to
      compositional changes and to structural disorder. The identification of both
      minerals was additionally supported by studying the powder X-ray diffraction
      diagrams.

PMID- 18722810
TI  - The interaction between pupil function and cardiovascular regulation in patients
      with acute schizophrenia.
AB  - OBJECTIVE: Cardiac autonomic dysregulation has been reported in patients with
      schizophrenia. However, there are no definite data examining whether other
      branches of the autonomic nervous system are compromised as well and how they
      interrelate with cardiac function. In this study, we tested the hypothesis that
      the autonomic dysregulation at the heart is reflected in the regulation of the
      pupillary light reflex. METHODS: We assessed heart rate variability and
      baroreflex sensitivity parameters as well as pupillographic measures in 28
      unmedicated patients with schizophrenia and compared these measures to those of
      28 controls. In addition, cardiovascular and pupillographic parameters were
      correlated in both groups. RESULTS: The obtained cardiovascular parameters
      indicated decreased parasympathetic modulation. Patients showed a significantly
      increased resting pupil diameter as well as reduced relative amplitude,
      suggesting a dominance of sympathetic control and a lack of parasympathetic
      modulation at the pupil. Intriguingly, the parasympathetic latency of the pupil
      constriction was similar in both groups and correlated with several
      cardiovascular parameters. These correlations were in the opposite direction in
      patients compared to controls. Furthermore, shorter latencies of the pupil
      constriction were associated with symptom severity in patients. CONCLUSIONS:
      Overall, we found evidence for an autonomic dysregulation at the pupil and heart
      in patients with schizophrenia. Future studies are warranted to describe this
      complex interaction at different levels of the autonomic system. SIGNIFICANCE:
      The interrelationship of both the systems indicates that the autonomic
      dysfunction affects the regulation in different branches of the autonomic network
      as well as their interaction in schizophrenia.

PMID- 18722811
TI  - Eosinophils and Trichinella infection: toxic for the parasite and the host?
AB  - Peripheral blood and tissue eosinophilia characterize trichinellosis in humans,
      and present in addition to the increased total IgE levels that occur in many
      helminth infections. Both processes are the consequence of T-helper 2 activation.
      Blood and tissue eosinophilia begins with eosinophilopoiesis in the bone marrow,
      which is followed by the migration of eosinophils through the circulatory system,
      the eosinophil infiltration of tissues at the inflammatory foci and, finally,
      degranulation and cell death. Recently, some aspects of eosinophilia caused by
      Trichinella spiralis infection have been elucidated; however, the protective role
      of this population of cells against Trichinella parasites remains controversial.
      Furthermore, when eosinophils are numerous, they can be toxic for host tissues.
      This review discusses these issues in both human and rodent infection models.

PMID- 18722813
TI  - Distance conservation of transcription regulatory motifs in human promoters.
AB  - To understanding the interaction network among transcription-regulation elements
      in human is an immediate challenge for modern molecular biology. Here a central
      problem is how to extract evolutionary information and search the evolutionary
      conservation from the comparison of promoters of closely related species. Through
      the comparative studies of k-mer distribution in human and mouse transcription
      factor binding site (TFBS) sequences we have discovered that the average distance
      between a pair of transcription regulatory 7-mer motifs is conservative in human
      mouse promoters. The distance conservation is a new kind of evolutionary
      conservation, not based on the strict location of bases in genome sequence. By
      utilizing the conservation of k-mer distance it will be helpful to propose a non
      alignment-based approach for fast genome-wide discovery of transcription
      regulatory motifs. We demonstrated the distance conservation by genome-wide
      searching of conservative regulatory 7-mer motifs with successful rate 90%. Then,
      after defining human-mouse pair-distance divergence parameter we studied the
      tissue-specific motif pairs and found that the parameter for motif pairs is 11-16
      times smaller than for their controls for 28 tissues and these pairs can be
      clearly differentiated on two-dimensional parameter plane. Finally, the mechanism
      of distance conservation was discussed briefly which is supposed to be related to
      the module structure of TFBSs.

PMID- 18722814
TI  - A feature vector integration approach for a generalized support vector machine
      pairwise homology algorithm.
AB  - Due to the exponential growth of sequenced genomes, the need to quickly provide
      accurate annotation for existing and new sequences is paramount to facilitate
      biological research. Current sequence comparison approaches fail to detect
      homologous relationships when sequence similarity is low. Support vector machine
      (SVM) algorithms approach this problem by transforming all proteins into a
      feature space of equal dimension based on protein properties, such as sequence
      similarity scores against a basis set of proteins or motifs. This multivariate
      representation of the protein space is then used to build a classifier specific
      to a pre-defined protein family. However, this approach is not well suited to
      large-scale annotation. We have developed a SVM approach that formulates remote
      homology as a single classifier that answers the pairwise comparison problem by
      integrating the two feature vectors for a pair of sequences into a single vector
      representation that can be used to build a classifier that separates sequence
      pairs into homologs and non-homologs. This pairwise SVM approach significantly
      improves the task of remote homology detection on the benchmark dataset,
      quantified as the area under the receiver operating characteristic curve; 0.97
      versus 0.73 and 0.70 for PSI-BLAST and Basic Local Alignment Search Tool (BLAST),
      respectively.

PMID- 18722812
TI  - Sex differences in stroke: epidemiology, clinical presentation, medical care, and
      outcomes.
AB  - Stroke has a greater effect on women than men because women have more events and
      are less likely to recover. Age-specific stroke rates are higher in men, but,
      because of their longer life expectancy and much higher incidence at older ages,
      women have more stroke events than men. With the exception of subarachnoid
      haemorrhage, there is little evidence of sex differences in stroke subtype or
      severity. Although several reports found that women are less likely to receive
      some in-hospital interventions, most differences disappear after age and
      comorbidities are accounted for. However, sex disparities persist in the use of
      thrombolytic treatment (with alteplase) and lipid testing. Functional outcomes
      and quality of life after stroke are consistently poorer in women, despite
      adjustment for baseline differences in age, prestroke function, and
      comorbidities. Here, we comprehensively review the epidemiology, clinical
      presentation, medical care, and outcomes of stroke in women.

PMID- 18722815
TI  - Sparse optimal scoring for multiclass cancer diagnosis and biomarker detection
      using microarray data.
AB  - Gene expression data sets hold the promise to provide cancer diagnosis on the
      molecular level. However, using all the gene profiles for diagnosis may be
      suboptimal. Detection of the molecular signatures not only reduces the number of
      genes needed for discrimination purposes, but may elucidate the roles they play
      in the biological processes. Therefore, a central part of diagnosis is to detect
      a small set of tumor biomarkers which can be used for accurate multiclass cancer
      classification. This task calls for effective multiclass classifiers with built
      in biomarker selection mechanism. We propose the sparse optimal scoring (SOS)
      method for multiclass cancer characterization. SOS is a simple prototype
      classifier based on linear discriminant analysis, in which predictive biomarkers
      can be automatically determined together with accurate classification. Thus, SOS
      differentiates itself from many other commonly used classifiers, where gene
      preselection must be applied before classification. We obtain satisfactory
      performance while applying SOS to several public data sets.

PMID- 18722817
TI  - Actigraphy quantifies reduced voluntary physical activity in women with primary
      dysmenorrhea.
AB  - We assessed whether an activity data logger was able to detect and measure the
      reduced physical activity reported by women with moderate to severe primary
      dysmenorrhea. Twelve young women with a history of primary dysmenorrhea and 12
      young women without a history of dysmenorrhea wore an activity data logger on
      their hip for 3 days when menstruating and for 3 matched days of the week when
      not menstruating. A visual analog scale was use to assess intensity of pain. When
      menstruating, the women with a history of primary dysmenorrhea, compared with
      when they were not menstruating, were significantly less active by about 40% on
      their day of worst pain (P < .001), day of intermediate pain (P < .001), and day
      of least pain (P < .001). There was no significant difference in the voluntary
      physical activity of the group on the 3 menstrual days. The women without a
      history of dysmenorrhea experienced mild menstrual pain but no significant
      decrease in physical activity (P = .82). We show that data loggers are able to
      detect and quantify the decrease in physical activity reported by the women with
      a history of moderate to severe dysmenorrhea and that menstrual pain but not
      menstruation itself was associated with decreased voluntary physical activity.
      PERSPECTIVE: We have shown that a miniature activity data logger, when worn on
      the hip of women with a history of dysmenorrhea, detected a 40% decrease in
      physical activity when the women were experiencing moderate to severe primary
      dysmenorrhea. Actigraphy is a useful tool for measuring pain-related debilitation
      and its management.

PMID- 18722816
TI  - Fundamental differences in the dynamics of CNS lesion development and composition
      in MP4- and MOG peptide 35-55-induced experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is characterized by a dynamic inflammatory process in
      which CNS lesions of distinct cellular composition coexist. In particular the
      formation of B cell plaques has been ascribed an important role as predictor of
      disease progression. Here we show that the novel MBP-PLP fusion protein (MP4)
      induced experimental autoimmune encephalomyelitis (EAE) of C57BL/6 mice fulfils
      these criteria inducing differential cellular infiltration of B cells, T cells,
      macrophages and granulocytes and permitting the quantification and staging of the
      disease. On the contrary, both key features - dynamic CNS inflammation and B cell
      infiltration - were absent in the classical MOG:35-55-induced EAE of C57BL/6
      mice, which was characterized by a static CD4(+) T cell and macrophage-mediated
      CNS immunopathology throughout the disease. MP4-induced EAE may thus provide a
      unique opportunity for studying immune-pathomechanisms of the disease that have
      been previously neglected due to experimental shortcomings in murine EAE.

PMID- 18722818
TI  - Reduction of pain-related fear and disability in post-traumatic neck pain: a
      replicated single-case experimental study of exposure in vivo.
AB  - For patients with acute post-traumatic neck pain (PTNP), pain-related fear has
      been identified as a potential predictor of chronic disability. If such is the
      case, fear reduction should enhance the prevention of further pain disability and
      distress after traumatic neck pain disability. However, exposure-based treatments
      have not been tested in patients with PTNP. Using a replicated single-case
      crossover phase design with multiple measurements, this study examined whether
      the validity of a graded exposure in vivo, as compared with usual graded
      activity, extends to PTNP. Eight patients who reported substantial pain-related
      fear were included in the study. Daily changes in pain intensity, pain-related
      fear, pain catastrophizing, and activity goal achievement were assessed. Before
      and after each intervention, and at 6-month follow-up, standardized
      questionnaires of pain-related fear and pain disability were administered, and,
      to quantify daily physical activity level, patients carried an ambulatory
      activity monitor. The results showed decreasing levels of self-reported pain
      related fear, pain intensity, disability, and improvements in physical activity
      level only when graded exposure in vivo was introduced, and not in the graded
      activity condition. The results are discussed in the context of the search for
      customized treatments for PTNP. PERSPECTIVE: This is the first study showing that
      the effects of graded exposure in vivo generalize to patients with chronic PTNP
      reporting elevated levels of pain-related fear. This could help clinicians to
      customize treatments for PTNP.

PMID- 18722819
TI  - The continuing saga of obesity and malnutrition.

PMID- 18722821
TI  - Achalasia and laparoscopic gastric bypass.

PMID- 18722820
TI  - Management of anastomotic leaks after Roux-en-Y bypass using self-expanding
      polyester stents.
AB  - BACKGROUND: To analyze the outcomes of a series of endoscopically placed
      polyester self-expanding polyflex stents (SEPSs) for the management of
      anastomotic leaks after Roux-en-Y bypass. Anastomotic leaks after gastric bypass
      cause significant morbidity and mortality. Covered polyester SEPSs might have a
      role in the treatment of these leaks. METHODS: A retrospective chart review was
      performed from January 2006 to November 2006 that included all acute and chronic
      leaks treated with SEPSs. RESULTS: A total of 6 patients were treated with
      stents, with a mean procedure time of 22 minutes. Of these 6 patients, 5 had
      acute postoperative leaks and 1 had a chronic fistula. Five patients started oral
      intake 1-6 days after their procedure. All acute leaks had complete healing at a
      median of 44 days. The patient with a chronic gastrocutaneous fistula required
      revisional surgery for fistula closure. In addition, 5 patients had stent
      migration, and 3 required stent replacement. CONCLUSION: An endoscopically placed
      SEPS provides a less-invasive alternative to treat acute anastomotic leaks after
      Roux-en-Y bypass while simultaneously allowing oral intake. The results of this
      case series have demonstrated this treatment to be safe and effective.

PMID- 18722823
TI  - Pulmonary function in the morbidly obese.
AB  - BACKGROUND: Only limited data exist on the relationship of lung function to
      patients with extreme obesity. To assess the relationship between lung function
      tests and clinical characteristics in a cohort of morbidly obese patients
      undergoing evaluation for bariatric procedures in a university hospital in the
      United States. METHODS: Consecutive patients undergoing clinical evaluation were
      reviewed. The variables included demographic, anthropometric, clinical, and
      pulmonary function data. RESULTS: A total of 229 patients underwent a
      standardized preoperative evaluation. Of these 229 patients, 136 (59%) had
      evaluable data and 102 (75%) were women. The mean +/- standard deviation age was
      45 +/- 10 years, the mean weight was 164 +/- 42 kg, and the mean body mass index
      was 57 +/- 13 kg/m2. Smoking or asthma was reported in 38% and 24% of patients,
      respectively. The mean forced vital capacity and forced expiratory volume in 1 s
      was 80% +/- 17% of predicted and 76% +/- 19% of predicted, respectively. Of the
      136 patients, 29% had a measured forced expiratory volume in 1 s/forced vital
      capacity of >or=.08 below the predicted ratio. The mean total lung capacity was
      86% +/- 14% of predicted; 26% of subjects had a total lung capacity <80% of
      predicted. Multivariate logistic regression analysis demonstrated an association
      of obstructive ventilatory defects with male gender (odds ratio [OR] 2.35, 95%
      confidence interval [CI] 1.00-5.50) and current or previous smoking (OR 2.41, 95%
      CI 1.10-5.30), but not body mass index. Restrictive defects were associated with
      body mass index (OR 1.06, 95% CI 1.01-1.10), in particular, obesity
      hypoventilation syndrome (OR 3.7, 95% CI 1.2-11.1). CONCLUSION: The mean
      preoperative spirometry, lung volumes, and gas exchange values were within the
      established reference ranges. Restrictive ventilatory defects were less common
      than obstructive ventilatory patterns and were most prominently associated with
      obesity hypoventilation syndrome.

PMID- 18722824
TI  - Parasympathetic response to acute stress is attenuated in young Zucker obese
      rats.
AB  - We compared arterial blood pressure (BP) and heart rate (HR) control in 9- to 11
      week old obese Zucker rats (n=10; weight=452+/-45 g, average+/-SD) to age
      matched, lean Zucker animals (n=13; weight=280+/-46 g). BP was measured by
      indwelling catheter. Baseline pressure was 113.1+/-7.0 mm Hg in the lean vs.
      111.7+/-5.6 in the obese rats (NS). Baseline HR was 413+/-43 in the lean vs.
      422+/-22 bpm in the obese animals (NS). Rats were classically conditioned by
      following a 15-second tone (CS+) with a 0.5-second tail shock. There were no
      between-group differences in the BP response to CS+. Conversely, heart rate (HR)
      decreased significantly (p<0.05) more during the last 10 s of the tone in the
      lean group (-46.0+/-21.5 bpm) vs. the obese (-17.8+/-21.7 bpm). This bradycardia
      was blocked by atropine. Finally, the change in HR divided by the change in
      arterial BP (DeltaHR/DeltaBP) following an intravenous bolus of phenylephrine
      (PE; 5 microg/kg) and following sodium nitroprusside (NP; 5 microg/kg) was
      determined. The DeltaHR/DeltaBP following PE was smaller in the obese (n=6; 
      1.36+/-0.60) vs. lean (n=5; -2.80+/-0.92); there was no difference in the
      response following NP. These data indicate that the BP response to a behavioral
      challenge did not differ in the obese rat vs. the lean animal, but that the obese
      subjects had an attenuated parasympathetic response to the stress, probably
      secondary to alterations in baroreflex function.

PMID- 18722825
TI  - Direct electrochemistry and electrochemical catalysis of myoglobin-TiO2 coated
      multiwalled carbon nanotubes modified electrode.
AB  - TiO(2) nanoparticles were homogeneously coated on multiwalled carbon nanotubes
      (MWCNTs) by hydrothermal deposition, and this nanocomposite might be a promising
      material for myoglobin (Mb) immobilization in view of its high biocompatibility
      and large surface. The glassy carbon (GC) electrode modified with Mb
      TiO(2)/MWCNTs films exhibited a pair of well-defined, stable and nearly
      reversible cycle voltammetric peaks. The formal potential of Mb in TiO(2)/MWCNTs
      film was linearly varied in the range of pH 3-10 with a slope of 48.65 mV/pH,
      indicating that the electron transfer was accompanied by single proton
      transportation. The electron transfer between Mb and electrode surface, k(s) of
      3.08 s(-1), was greatly facilitated in the TiO(2)/MWCNTs film. The
      electrocatalytic reductions of hydrogen peroxide were also studied, and the
      apparent Michaelis-Menten constant is calculated to be 83.10 microM, which shows
      a large catalytic activity of Mb in the TiO(2)/MWCNTs film to H(2)O(2). The
      modified GC electrode shows good analytical performance for amperometric
      determination of hydrogen peroxide. The resultant Mb-TiO(2)/MWCNTs modified
      glassy carbon electrode exhibited fast amperometric response to hydrogen peroxide
      reduction, long term life and excellent stability. Finally the activity of the
      sensor for nitric oxide reduction was also investigated.

PMID- 18722826
TI  - Electrochemical and ultraviolet-visible spectroscopic studies on the interaction
      of deoxyribonucleic acid with vitamin B6.
AB  - Studies on the interaction of DNA with vitamin B(6) were carried out with a DNA
      modified electrode by electrochemistry and Ultraviolet-visible spectroscopy. The
      results showed that there exists the supra-molecule interaction between base
      groups on DNA and vitamin B(6) by forming hydrogen binding, the binding
      equilibrium constant of the interaction is equal to 115.3 M(-1), the binding
      ratio of nucleotide to vitamin B(6) is 5:1. Based on the electrochemical and
      Ultraviolet-visible spectrum studies the interaction mode of DNA with vitamin
      B(6) was explored.

PMID- 18722827
TI  - Development and implementation of a stereoselective normal-phase liquid
      chromatography-tandem mass spectrometry method for the determination of intrinsic
      metabolic clearance in human liver microsomes.
AB  - The stereoselective determination of stereoisomers in biological samples provides
      vital information on stereospecific metabolism and pharmacokinetic profiles of
      the drugs. Despite the unique advantage and the great success of normal-phase
      (NP) HPLC for the separations of drug stereoisomers using polysaccharide-type
      chiral stationary phases (CSPs), the technique is rarely applied to quantitative
      HPLC-MS-MS bioanalysis. This is, at least in part, due to the incompatibility
      between the usual mobile phase (n-hexane or n-heptane) in normal-phase HPLC and
      the MS ionization sources which poses a potential detonation hazard. An
      environmentally friendly and nonflammable alternative solvent,
      ethoxynonafluorobutane (ENFB), was reported previously to potentially provide an
      ideal solution for combining the powers of stereoselective NP chromatographic
      separation and MS-MS detection. In this study, a stereoselective NP-HPLC-MS-MS
      method was developed using ENFB to quantify a pair of Bristol Myers Squibb (BMS)
      proprietary drug stereoisomers and their ketone metabolite for an in vitro study,
      which demonstrated, for the first time, the practical applicability and utility
      of ENFB for bioanalysis in pharmaceutical industry. The effects of different
      organic modifiers and temperature, as well as the comparison between ENFB and the
      usual solvent, heptane, for the separation, are discussed. The resolution of the
      stereoisomers was achieved using 63% of 3:1 mixture of ethanol and methanol with
      37% ENFB on a Chiralpak AD-H column at 50 degrees C. High sensitivity was
      obtained using the MS-MS detection in the positive ion atmospheric pressure
      chemical ionization (APCI) mode. The lower limit of quantitation (LLOQ) for the
      first stereoisomer and the ketone metabolite was 5 ng/mL, and was 10 ng/mL for
      the second isomer in the human liver microsome-potassium phosphate buffer matrix.
      The linear dynamic range of 5-1000 ng/mL for both isomers and 10-1000 ng/mL for
      the metabolite were demonstrated with R2 > or =0.997. The precision of the
      analysis was <5% R.S.D. at or above the nominal concentration of 80 ng/mL, and
      <20% R.S.D. at 8 ng/mL. The mean bias was less than 15%. Extraction recovery and
      acceptable matrix interference were demonstrated using one isomer and the ketone,
      and better than 75% recovery and less than 25% ion suppression or interference
      were found. The method was successfully implemented for an in vitro intrinsic
      metabolic clearance study.

PMID- 18722828
TI  - A novel software tool for high throughput measurements of interconversion
      barriers: DCXplorer.
AB  - The software program DCXplorer is introduced to directly access interconversion
      rate constants in dynamic chromatography and electrophoresis. The program
      utilizes the unified equation of chromatography which can evaluate reaction rate
      constants of all kinds of first order reactions of processes taking place during
      a separation process. Evaluations with DCXplorer are facilitated by a graphical
      user interface which allows zooming into the area of interest of an
      interconversion profile and calculating reaction rate constants without a time
      consuming simulation process. DCXplorer was applied to determine the
      enantiomerization barrier of the diuretic drug chlorthalidone by pressure
      supported dynamic capillary electrokinetic chromatography (DEKC) under acidic
      conditions at pH 5.00 and pH 3.75. Activation parameters DeltaH(++) and
      DeltaS(++) were obtained from temperature dependent measurements between 15.0 and
      35.0 degrees C in 5 K steps at pH 3.75 and between 30.0 and 50.0 degrees C in 10K
      steps at pH 5.00.

PMID- 18722829
TI  - Closure of a contained open abdomen using a bipedicled myofascial oblique rectus
      abdominis flap technique.
AB  - A contained open abdomen is commonly used during damage control laparotomy and
      consists of the temporary coverage of the abdomen for protection of the viscera
      and reduction of intra-abdominal pressure. Definitive closure of a contained open
      abdomen is technically difficult due to the inability to obtain primary fascial
      suture. The insertion of a prosthetic mesh can be complicated with
      enterocutaneous fistula, and other definitive closure techniques need several
      surgical procedures. We describe a low cost technique that allows definitive
      closure of large abdominal wall defects avoiding the risk of intestinal fistula.

PMID- 18722830
TI  - Reversed flow lateral circumflex femoral turnover technique for microsurgical
      anastomosis at the hip.

PMID- 18722832
TI  - Summer reading.

PMID- 18722833
TI  - Differing views on the BSN as the entry level into nursing practice.

PMID- 18722834
TI  - Differing views on the BSN as the entry level into nursing practice.

PMID- 18722835
TI  - Evaluating the evidence: guidelines.
AB  - Guidelines are collections of practical information that assist with clinical
      decision making. Evidence-based guideline development includes a critique of the
      quality and an evaluation of the strength of published evidence. Evolution From
      opinion-based to evidence-based guidelines is incomplete in many of the
      organizations that author them, so perioperative nurses must become skillful at
      critiquing guideline development methodologies and clinical content. The AGREE
      instrument is useful for evaluating guideline development. Nurses have access to
      evidence-based guidelines registered online through the National Guideline
      Clearinghouse.

PMID- 18722836
TI  - Natural rubber latex: a matter of concern for nurses.
AB  - During the past 20 years, the use of protective gloves in health care has
      increased, as have hypersensitivity reactions to the natural rubber latex (NRL)
      used in glove manufacture. A study was conducted to determine what nurses who
      work in environments in which NRL is commonly used know about NRL, including
      their education about and experience with NRL-related allergies. Nurses replied
      to a questionnaire with 20 statements pertaining to NRL and NRL-related
      allergies. The results showed that the nurses had inadequate knowledge about NRL,
      but nurses in a specialty training program scored significantly higher than
      professionally active nurses.

PMID- 18722837
TI  - Shifting the sterile processing department paradigm: a mandate for change.
AB  - Sterile processing department (SPD) staff members have the difficult task of
      processing complicated instrumentation, containing costs, and managing limited
      resources; and how they face these challenges has a direct effect on patient
      care. Recent technological advances require SPD staff members to be more
      knowledgeable about what instrument trays are used together and the conditions in
      which they are used to help prevent costly delays in processing. This article
      explores how one health care system was successful in facing these challenges by
      implementing a solid orientation and education program.

PMID- 18722838
TI  - Controlled-substance returns in the operating suite.
AB  - Drug diversion is an ongoing problem in health care settings. The potential for
      drug diversion incidents in the perioperative area is high because of the
      availability of narcotics and other controlled substances and the stresses of
      working in this environment. The flow of controlled substances traditionally has
      been monitored by various accounting systems, but these systems can be inaccurate
      because the returned medications rarely are tested to verify that they have not
      been diluted or replaced. Returned medications are not routinely tested because
      of the expense and time involved. Enhanced photoemission spectroscopy is one
      technology that can validate returned medications quickly and inexpensively.

PMID- 18722839
TI  - Using servant leadership to facilitate healing after a drug diversion experience.
AB  - Although much has been written about substance abuse in nursing, little attention
      has been paid to the reaction of a nurse's coworkers after he or she has been
      caught diverting drugs. The remaining staff members may enter into a grieving
      process, which can have a serious effect on the delivery of patient care and
      staff satisfaction. Devoting time and energy to addressing the challenges faced
      by staff members after a drug diversion experience is essential to reestablishing
      equilibrium in the department. Using the servant leadership model, managers can
      exemplify the characteristics of commitment, persuasion, awareness, and foresight
      to facilitate the grieving process and solidify staff cohesion to help ensure
      quality patient care.

PMID- 18722840
TI  - Standardization of a surgical site precleansing technique for vascular patients.
AB  - Surgical site infection (SSI) is a serious complication that can increase
      hospital costs and length of stay and may be life threatening. The preoperative
      chlorhexidine shower is widely recommended to decrease SSI risk, although
      standardized guidelines for this practice and supporting clinical evidence are
      lacking. Because vascular patients often have comorbidities that hinder
      preoperative showering, OR nurses at a specialty hospital in Dallas, Texas,
      developed and implemented an intraoperative surgical site precleansing technique
      as standard practice for patients undergoing procedures involving the axilla or
      groin.

PMID- 18722841
TI  - Providing developmentally based care for preschoolers.

PMID- 18722843
TI  - Preventing deep vein thrombosis: a perioperative nursing imperative.

PMID- 18722845
TI  - Welcome clinical leadership at NICE.

PMID- 18722846
TI  - WHO AFRO's chance to shine.

PMID- 18722847
TI  - Women should be offered post-abortion psychological care.

PMID- 18722848
TI  - Face transplantation.

PMID- 18722849
TI  - A king in the CASTLE? Optimum initial HIV protease inhibitor.

PMID- 18722850
TI  - Did the drug cause death? Codeine and breastfeeding.

PMID- 18722851
TI  - Declining breast cancer incidence and decreased HRT use.

PMID- 18722852
TI  - Antiepileptic drug withdrawal in seizure-free patients.

PMID- 18722853
TI  - Health economics and prioritising health care.

PMID- 18722854
TI  - Human papillomavirus vaccination: stabbing in the dark?

PMID- 18722855
TI  - Kgosi Letlape.

PMID- 18722856
TI  - Inflammation.

PMID- 18722857
TI  - Codeine and breastfeeding.

PMID- 18722859
TI  - Lack of publication bias related to results from trastuzumab study.

PMID- 18722860
TI  - Transport policy, food policy, obese people, and victim blaming.

PMID- 18722861
TI  - Futures and food prices.

PMID- 18722862
TI  - Food, fuel, and health.

PMID- 18722865
TI  - MVP and vinorelbine for malignant pleural mesothelioma.

PMID- 18722866
TI  - Medical research in the Darzi review.

PMID- 18722867
TI  - Human facial allotransplantation: a 2-year follow-up study.
AB  - BACKGROUND: Progress in composite tissue allotransplantation could provide a new
      treatment for patients with severe facial disfigurements. We did a partial facial
      allotransplantation in 2006, and report here the 2 year follow-up of the patient.
      METHODS: The recipient, a 30-year-old man from China, had his face severely
      injured by a bear in October, 2004. Allograft composite tissue transplantation
      was done in April, 2006, after careful systemic preparation. The surgery included
      anastomosis of the right mandibular artery and anterior facial vein, whole repair
      of total nose, upper lip, parotid gland, front wall of the maxillary sinus, part
      of the infraorbital wall, and zygomatic bone. Facial nerve anastomosis was done
      during the surgery. Quadruple immunomodulatory therapy was used, containing
      tacrolimus, mycophenolate mofetil, corticosteroids, and humanised IL-2 receptor
      monoclonal antibody. Follow-up included T lymphocyte subgroups in peripheral
      blood, pathological and immunohistochemical examinations, functional progress,
      and psychological support. FINDINGS: Composite tissue flap survived well. There
      were three acute rejection episodes at 3, 5, and 17 months after transplantation,
      but these were controlled by adjustment of the tacrolimus dose or the application
      of methylprednisolone pulse therapy. Hepatic and renal functions were normal, and
      there was no infection. The patient developed hyperglycaemia on day 3 after
      transplantation, which was controlled by medication. INTERPRETATION: Facial
      transplantation could be successful in the short term, but the procedure was not
      without complications. However, promising results could mean that this procedure
      might be an option for long-term restoration of severe facial disfigurement.

PMID- 18722868
TI  - Repair of the lower and middle parts of the face by composite tissue
      allotransplantation in a patient with massive plexiform neurofibroma: a 1-year
      follow-up study.
AB  - BACKGROUND: The risk to benefit ratio of face transplantation with a composite
      tissue allograft remains debatable, although this procedure is technically
      feasible. We report here a 1-year follow-up of a patient who underwent face
      transplantation with a composite tissue allograft. METHODS: On Jan 21, 2007, a 29
      year-old man with neurofibromatosis type 1 underwent resection of a massive
      plexiform neurofibroma diffusely infiltrating the middle and lower part of his
      face. The main goal was to restore both the cutaneous appearance and function of
      the face, including, in particular, control of orbicularis oculi and oris muscle
      contraction. The issues of immunosuppressive therapy, psychological outcome, and
      social reintergration were addressed, together with the monitoring of graft
      rejection by biopsies of the skin and mucosa. FINDINGS: The initial postoperative
      course was uncomplicated. Two episodes of clinical rejection occurred on days 28
      and 64. The second episode was associated with cytomegalovirus infection. Both
      episodes resolved favourably, with no further clinical signs of rejection, making
      the reduction of immunosuppressive treatment possible. A year after surgery, the
      functional outcome was very good, with successful sensory and motor reinnervation
      in the transplanted territory. Psychological recovery was excellent, with
      complete social reintegration. INTERPRETATION: This case demonstrates the
      feasibility of surgically removing a large part of the face and replacing it with
      a composite tissue allograft. This facial repair procedure, which seems to have a
      satisfactory risk to benefit ratio, could be offered in rare and selected cases.

PMID- 18722870
TI  - The dire consequences of doping.

PMID- 18722869
TI  - Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in
      combination with tenofovir and emtricitabine, for management of antiretroviral
      naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE
      study.
AB  - BACKGROUND: Atazanavir/ritonavir is as effective as lopinavir/ritonavir, with a
      more favourable lipid profile and less gastrointestinal toxicity, in treatment
      experienced HIV-1-infected patients. We compared these two combinations directly
      in treatment-naive patients. METHODS: In this open-label, international non
      inferiority study, 883 antiretroviral-naive, HIV-1-infected patients were
      randomly assigned to receive atazanavir/ritonavir 300/100 mg once daily (n=440)
      or lopinavir/ritonavir 400/100 mg twice daily (n=443), in combination with fixed
      dose tenofovir/emtricitabine 300/200 mg once daily. Randomisation was done with a
      computer-generated centralised randomisation schedule and was stratified by
      baseline levels of HIV RNA (viral load) and geographic region. The primary
      endpoint was the proportion of patients with viral load less than 50 copies per
      mL at week 48. The main efficacy analysis was done by intention to treat. This
      trial is registered with ClinicalTrials.gov, number NCT00272779. FINDINGS: At
      week 48, 343 (78%) of 440 patients receiving atazanavir/ritonavir and 338 (76%)
      of 443 patients receiving lopinavir/ritonavir had achieved a viral load of less
      than 50 copies per mL (difference 1.7%, 95% CI -3.8 to 7.1). Mean increases from
      baseline in CD4 cell count were similar (203 cells per muL in the
      atazanavir/ritonavir group vs 219 cells per muL in the lopinavir/ritonavir
      group). 25 (6%) patients in the atazanavir/ritonavir group and 26 (6%) in the
      lopinavir/ritonavir group were virological failures by week 48. Only two
      patients, both in the atazanavir/ritonavir group, had non-polymorphic protease
      inhibitor resistance mutations emerge on treatment, which conferred phenotypic
      resistance to atazanavir in one patient. Serious adverse events were noted in 51
      (12%) of 441 patients in the atazanavir/ritonavir group and in 42 (10%) of 437
      patients in the lopinavir/ritonavir group. Fewer patients in the
      atazanavir/ritonavir group than in the lopinavir/ritonavir group experienced
      grade 2-4 treatment-related diarrhoea (10 [2%] vs 50 [11%]) and nausea (17 [4%]
      vs 33 [8%]). Grade 2-4 jaundice was seen in 16 (4%) of 441 patients in the
      atazanavir/ritonavir group versus none of 437 patients in the lopinavir/ritonavir
      group; grade 3-4 increases in total bilirubin were seen in 146 (34%) of 435
      patients on atazanavir/ritonavir and in one (<1%) of 431 patients on
      lopinavir/ritonavir. INTERPRETATION: In treatment-naive patients,
      atazanavir/ritonavir once-daily demonstrated similar antiviral efficacy to
      lopinavir/ritonavir twice-daily, with less gastrointestinal toxicity but with a
      higher rate of hyperbilirubinaemia.

PMID- 18722871
TI  - Tuberous sclerosis.
AB  - Tuberous sclerosis is a genetic multisystem disorder characterised by widespread
      hamartomas in several organs, including the brain, heart, skin, eyes, kidney,
      lung, and liver. The affected genes are TSC1 and TSC2, encoding hamartin and
      tuberin respectively. The hamartin-tuberin complex inhibits the mammalian-target
      of-rapamycin pathway, which controls cell growth and proliferation. Variations in
      the distribution, number, size, and location of lesions cause the clinical
      syndrome to vary, even between relatives. Most features of tuberous sclerosis
      become evident only in childhood after 3 years of age, limiting their usefulness
      for early diagnosis. Identification of patients at risk for severe manifestations
      is crucial. Increasing understanding of the molecular abnormalities caused by
      tuberous sclerosis may enable improved management of this disease.

PMID- 18722872
TI  - Management of patients with head injury.

PMID- 18722873
TI  - Flu-like illness--and a rash.

PMID- 18722874
TI  - No association between epidermal growth factor and epidermal growth factor
      receptor polymorphisms and nasopharyngeal carcinoma.
AB  - Numerous candidate genes have been proposed as susceptibility factors for the
      development of nasopharyngeal carcinoma (NPC). Epidermal growth factor (EGF) and
      epidermal growth factor receptor (EGFR) interaction plays a pivotal role in cell
      proliferation, differentiation, and tumourigenesis of epithelial tissues. To our
      knowledge, however, no study has examined the relationship between the EGF/EGFR
      and NPC. The aim of this study is to investigate the potential association
      between single-nucleotide polymorphisms of EGF +61 G/A and EGFR +2073 A/T and
      NPC. A total of 173 patients with NPC and 206 age- and sex-matched controls were
      the participants. Genotypes were determined using a polymerase chain reaction
      restriction fragment length polymorphism strategy and DNA sequencing. There were
      no significant differences in the genotype and allele frequencies of EGF +61 G/A
      and EGFR +2073 A/T polymorphisms between the group of patients with NPC and the
      control group in a Chinese population (for EGF +61 G/A: OR=1.29, 95% CI: 0.95
      1.74; for EGFR +2073 A/T: OR=0.91, 95% CI: 0.67-1.23). Further studies are still
      needed to explore the complicated interaction between environmental factors and
      EGF +61 G/A and EGFR +2073 A/T polymorphisms in the risk of NPC, particularly in
      ethnically different populations.

PMID- 18722875
TI  - An endometrial stromal sarcoma cell line with the JAZF1/PHF1 chimera.
AB  - Endometrial stromal sarcomas (ESS) are rare malignancies, accounting for less
      than 10% of uterine sarcomas. Apart from the chromosomal rearrangement
      t(7;17)(p15;q21), which leads to the JAZF1/SUZ12 chimera, cytogenetic studies
      have shown that the chromosome band 6p21 is often rearranged in ESS. The
      translocation partners involved in the 6p21 rearrangements differ among the
      tumors, but chromosome 7 is involved in most aberrations. A JAZF1/PHF1 fusion
      gene was recently found in two tumors showing an exchange between 6p and 7p
      rearrangement. In the present study, we show that a low-grade ESS cell line
      carrying a der(7)t(6;7)(p21;p22) also harbors the a JAZF1/PHF1 fusion. In the
      fusion transcript, exon 3 of JAZF1 was fused with exon 2 of PHF1. At the
      junction, there was an insertion of 26 nucleotides, originating from intron 3 of
      JAZF1, thus maintaining an open reading frame of the chimeric transcript. The
      predicted 684-amino acid JAZF1/PHF1 chimeric protein retained one zinc finger
      domain from JAZF1 and the two zinc finger domains from PHF1, and its oncogenic
      mechanism should be similar to that of the JAZF1/SUZ12 protein. The present cell
      line constitutes an excellent model for further studies on the impact of the
      JAZF1/PHF1 fusion.

PMID- 18722876
TI  - Role of hormonal genes and risk of prostate cancer: gene-gene interactions in a
      North Indian population.
AB  - Prostate cancer represents a heterogeneous disease with varying degrees of
      aggressiveness, patterns of metastasis, and response to therapy. It arises from a
      complex etiology that involves both exogenous (diet, environment, etc.) and
      endogenous (hormonal and genetic) factors. The present study was performed to
      explore the role of various genotypes involved in steroid metabolism and
      synthesis in the causation of prostate cancer. Genetic polymorphism of the ER,
      CYP17, SRD5A2 (TA repeats), and PSA genes were analyzed in 157 cases of prostate
      cancer and 340 controls [170 healthy males and 170 patients of benign prostate
      hyperplasia (BPH)]. Mutant genotypes of ER and CYP17 showed 2- and 3- and 3.5
      fold increased risk of prostate cancer, respectively, as compared to BPH and
      healthy controls. Interaction of mutant (homozygous and heterozygous) alleles of
      CYP17 with TA (0/0) led to a twofold increased risk of prostate cancer. Risk was
      more than twofold with the combination of mutant alleles of ER and CYP17. The PSA
      gene polymorphism did not show any increased risk of prostate cancer. This
      indicates the role of mutant allele of ER and CYP17 in the development and
      progression of prostate cancer and rules out any increased risk with PSA
      polymorphism in the north Indian population.

PMID- 18722877
TI  - Functional copy number changes in Sezary syndrome: toward an integrated molecular
      cytogenetic map III.
AB  - Sezary syndrome (SS) is a rare form of cutaneous T-cell lymphomas (CTCL)
      manifested by generalized exfoliative erythroderma, intense pruritus, peripheral
      lymphadenopathy, and abnormal hyperchromatic mononuclear cells in the skin, lymph
      nodes, and peripheral blood. Previous studies have revealed complex genetic
      aberrations affecting almost all chromosomes with up- and down-regulation of
      several genes in this subtype of CTCL. It is still unclear, however, which of
      these genetic alterations are the primary changes and which are the secondary
      ones. We have long thought that a key molecular defect should be consistently
      present at DNA, RNA, and protein levels. We therefore assume that some chromosome
      copy number changes (CNC) seen in cancer cells may have a direct impact on gene
      expression pattern and that these CNC are presumably functional. To test this
      hypothesis, we designed a simple but novel boinformatic method that included
      analysis of SS gene expression microarray raw data, generation of gene lists from
      the chromosomal regions showing significant CNC in SS, and data remaining to
      establish if the CNC gene lists affected gene clustering in terms of separation
      of SS cases from the normal controls or not. The bioinformatic analysis of 17
      selected gene lists with GeneSpring software showed that four (24%) from copy
      number losses at 1p36p22, 6q24, and 15q11.2, as well as gains at 22q11.2q13.3,
      were capable of separating all six SS cases from two controls (P<0.05), and some
      of the genes, such as LCK at 1p34.3, may have implications in CTCL. The remaining
      13 gene lists produced a mixed gene clustering patterns between SS cases and
      normal control samples (P<<0.01). These findings suggest that CNC from these
      chromosomal regions may be functional and relevant to SS.

PMID- 18722878
TI  - Occurrence of trisomy 12, t(14;18)(q32;q21), and t(8;14)(q24.1;q11.2) in a
      patient with B-cell chronic lymphocytic leukemia.
AB  - Trisomy 12, t(14;18)(q32;q21), and t(8;14)(q24.1;q11.2) were found in a 59-year
      old man with B-cell chronic lymphocytic leukemia (CLL). While trisomy 12 is one
      of the most common cytogenetic abnormalities in chronic lymphocytic leukemia, the
      t(14;18) rearrangement has a strong association with follicular lymphoma and the
      t(8;14) is associated with T-cell neoplasia. Occurrence of these three
      abnormalities in CLL are rare, and the significance of this finding is unclear.
      Further studies of similar cases may shed additional insight into this finding.

PMID- 18722879
TI  - A new dic(7;12)(p12.21;p12.2) chromosome aberration in a case of acute myeloid
      leukemia.
AB  - A new dic(7;12)(p12.21;p12.2) chromosome aberration was identified in an acute
      myeloid leukemia with FAB-M1 morphology and was cloned. Fluorescence in situ
      hybridization and genomic quantitative polymerase chain reaction mapping
      experiments revealed the precise localization of the breakpoints, at 7p12, just
      5' to the GRB10 gene, and 12p11, within a genomic region containing no known
      genes. As a result, a new dicentric chromosome is created, dic(7;12), with the
      consequent deletion of 50 Mb at 7p, from the telomere to the GRB10 region, and of
      30 Mb at 12p, from the telomere to p11. Several genes are included in the
      affected areas.

PMID- 18722880
TI  - A case of chronic myelogenous leukemia with e8a2 fusion transcript.
AB  - The Philadelphia chromosome and its corresponding fusion gene, BCR-ABL, is one of
      the best-known genetic abnormalities in hematological malignancies. Major BCR-ABL
      translocation is much more common in chronic myelogenous leukemia (CML) and minor
      BCR-ABL in acute lymphoblastic leukemia. We experienced an extraordinarily rare
      case of CML with an e8a2 variant. An unusual band, other than the common
      transcripts, was observed in reverse transcription-polymerase chain reaction (RT
      PCR) for the BCR-ABL gene rearrangement. Sequence analysis of the PCR product
      revealed an 1172-bp e8a2 fusion with a 14-bp insertion of ABL intron Ia. The
      patient achieved a complete hematological response 3 months after imatinib
      treatment. It is necessary to keep in mind that an unexpected band revealed with
      RT-PCR may mean the presence of unusual fusion gene.

PMID- 18722881
TI  - Complex t(8;19;21)(q22;p13;q22) as a sole abnormality in a patient with de novo
      acute myeloid leukemia.

PMID- 18722882
TI  - Cell-cell fusion is the rate-limiting step in causation and progression of
      clinically significant cancers.

PMID- 18722883
TI  - Mutational analysis of the CITED4 gene in glioblastomas.

PMID- 18722884
TI  - Migraine and audiovestibular dysfunction: is there a correlation?
AB  - PURPOSE: To study the audiovestibular functions in cases of migraine with or
      without vertigo. MATERIALS AND METHODS: This was a prospective study involving 50
      cases of migraine who were divided into 2 groups: patients with vertigo and those
      without. All patients underwent a detailed otological and neurootological
      examination followed by full audiological and vestibular investigation including
      pure tone audiometry, speech reception threshold, speech discrimination score,
      tone decay, short increment sensitivity index, auditory brainstem-evoked
      responses, and electronystagmography (ENG). RESULTS: Thirty-eight (76%) of 50
      patients had vertigo on presentation, of which rotatory nonpositional vertigo
      (22/38) was the most common. Phonophobia was the most common auditory symptom
      (35/50, 70%) followed by tinnitus (25/50, 50%). Only 17 patients (34%) reported
      hearing loss, of whom only 7 had documented hearing loss on pure tone audiometry.
      However, the auditory brainstem-evoked responses of all these patients showed
      some abnormalities in the form of prolonged absolute latency or prolonged
      interwave peak latencies or both. Electronystagmography revealed canal paresis in
      13 patients (26%), although there was no statistical difference between patients
      with or without vertigo on various electronystagmographic parameters. CONCLUSION:
      Auditory brainstem-evoked response abnormalities may be the earliest indicator of
      impending auditory involvement in migraine.

PMID- 18722885
TI  - Histopathologic changes in guinea pig mastoid mucosa after topical mitomycin C
      application followed by mastoidectomy.
AB  - PURPOSE: This study was performed to investigate the histopathologic changes
      observed in mastoid cavity of guinea pigs after the application of mitomycin C
      after mastoidectomy. MATERIALS AND METHODS: The study was performed on 50 guinea
      pigs. Unilateral (right ear) mastoidectomy was performed on all guinea pigs.
      Twenty-five guinea pigs were separated as study group and the remaining were
      separated as control group. A mitomycin C-soaked sponge was placed in the mastoid
      cavities of the study group and a dry sponge was placed in those of the control
      group. Their mastoid cavities were examined histopathologically for absorbable
      sponge waste, abscess formation, fibrosis, vascularization, polymorphonuclear
      leukocyte infiltration, edema, lymphoplasmacytic inflammatory infiltration, and
      granulation tissue. RESULTS: Absorbable sponge waste, abscess formation,
      fibrosis, vascularization, edema, and lymphoplasmacytic inflammatory infiltration
      were not significantly different between the groups. However, polymorphonuclear
      leukocyte infiltration and granulation tissue were statistically different
      between the groups. CONCLUSION: Mitomycin C can be used after mastoidectomy to
      decrease the granulation tissue formation in ear discharges and to prevent the
      discharge.

PMID- 18722886
TI  - Role of spiral computed tomography with 3-dimensional reconstruction in cases
      with laryngeal stenosis--a radioclinical correlation.
AB  - PURPOSE: To study the efficacy of spiral computed tomography with 3-dimensional
      reconstruction (SCT-3DI) and endoscopy in cases with laryngeal stenosis with
      regard to site, type, grade, and length of stenosis and to determine the
      correlation among the findings of SCT-3DI, endoscopy, and surgery. MATERIAL AND
      METHODS: This prospective study on 30 cases of laryngotracheal stenosis (acquired
      = 28 cases, congenital = 2 cases) was conducted in the Department of
      Otorhinolaryngology and Head Neck Surgery, Postgraduate Institute of Medical
      Education and Research, Chandigarh, India, from 2001 to 2003. All patients were
      evaluated by SCT-3DI and rigid endoscopy. Twenty-three patients underwent open
      surgical procedure, and 7 patients underwent endoscopic dilatation. Correlation
      was established among the findings of SCT-3DI, endoscopy, and surgery by Pearson
      correlation coefficient (r), paired t test, and chi(2) test. RESULTS: Findings of
      SCT-3DI, endoscopy, and surgery were found to well correlate with each other. SCT
      3DI was found to be less accurate in measuring the exact length of stenosis but
      could measure the length of stenosis in all cases, whereas by endoscopy, the
      measurements could be made accurately in 14 cases (46.6%). The endoscopy was more
      accurate in diagnosing the site and grade of stenosis (P < .01). SCT-3DI gave
      18.6% false-positive result regarding involvement of glottis in stenosis. A
      significant difference was found between endoscopy and SCT-3DI for grade III and
      IV stenoses (P < .01), and SCT-3DI found to give false-positive result in 19.2%
      cases for grade IV stenosis. SCT-3DI was found to be a better diagnosing modality
      in differentiating the circumferential Gupta and Parida. SCT-3DI was found to
      give a false-positive result in 19.2% cases for grade IV stenosis. SCT-3DI was
      found to be better a diagnosing modality in differentiating the circumferential
      and eccentric stenosis (P < .01) and to detect the cricoid and thyroid cartilage
      fracture, double stenosis, and laryngocele. A false-positive rate of 33.3% was
      seen in diagnosing fracture of cricoid cartilage on radiology. CONCLUSION: The
      findings of SCT-3DI, endoscopy, and surgery well correlated with each other.
      Findings of SCT-3DI and rigid endoscopy are complementary to each other for a
      better surgical planning and outcome.

PMID- 18722887
TI  - Irradiated macula flava in the human vocal fold mucosa.
AB  - PURPOSE: There have been no investigations regarding radiation-induced damage on
      human maculae flavae (MFs) in the vocal fold mucosa (VFM) and on stellate cells
      (SC) in the MF. The VFM, especially MF, after irradiation was investigated
      histologically. MATERIALS AND METHODS: The lamina propria of the irradiated VFM
      was investigated in 5 human adult vocal folds by light and electron microscopy.
      RESULTS: Fibroblasts in the irradiated Reinke's space (RS) showed no
      morphological changes. Irradiated RS was composed of fibrous tissue with
      increased collagenous fibers. Most of the SC in the irradiated MF had dark
      cytoplasm. The nucleus-cytoplasm ratio was relatively small, but there were few
      intracellular organelles in the cytoplasm. Some SC showed degeneration. Fewer
      vesicles were present at the periphery of the cytoplasm. The MF was rather
      deficient in fibrous components. Elastic and collagenous fibers immediately
      surrounding SC in the irradiated MF were lower in number than usual, but elastic
      fibers and collagenous fibers composed of irregular collagen fibrils could be
      detected at a distance from SC. It was suggested that precursors of collagenous
      and elastic fibers synthesized by SC were damaged by irradiation. Radiation
      sensitivity of SC was higher than that of conventional fibroblasts in RS, and SC
      appeared to decrease their level of activity. CONCLUSIONS: Radiation sensitivity
      of SC was different from that of conventional fibroblasts. Radiation induced not
      only changes in the lamina propria of the VFM but also dysfunction of the SC in
      the MF, and is one of the causes of voice disorders after irradiation.

PMID- 18722888
TI  - Klippel-Feil syndrome and associated ear anomalies.
AB  - BACKGROUND AND PURPOSE: Klippel-Feil syndrome (KFS) is a congenital segmentation
      anomaly of the cervical vertebrae that manifests as short neck, low hair line,
      and limited neck mobility. Various systemic malformations may also accompany the
      syndrome including wide variety of otopathologies affecting all 3 compartments of
      the ear (external, middle, and inner ear) as well as internal acoustic canal and
      vestibular aqueduct. We aimed to investigate these involvements and their
      clinical correlates in a group of patients with KFS. MATERIALS, METHODS, AND
      RESULTS: We present 20 KFS cases, of which 12 (% 60) displayed most of the
      reported ear abnormalities such as microtia, external ear canal stenosis, chronic
      ear inflammations and their sequels, anomalies of the tympanic cavity and
      ossicles, inner ear dysplasies, deformed internal acoustic canal, and wide
      vestibular aqueduct, which are demonstrated using the methods of otoscopy,
      audiologic testing, and temporal bone computed tomography. CONCLUSIONS: This
      series represents one of the highest reported rate of ear involvement in KFS. We
      found no correlation between the identified ear pathologies and the skeletal and
      extraskeletal malformations. The genetic nature of the syndrome was supported by
      the existence of affected family members in 4 (20%) of the cases.

PMID- 18722889
TI  - Non-sinusitis-related rhinogenous headache: a ten-year experience.
AB  - PURPOSE: This study aimed to investigate the role of anatomical abnormalities in
      non-sinusitis-related rhinogenous headache and to evaluate response to surgery.
      MATERIALS AND METHODS: Between January 1995 and December 2004, 71 patients were
      diagnosed with non-sinusitis-related rhinogenous headache preoperatively and
      treated with endoscopic sinus surgery and/or septoplasty if other underlying
      diseases could be ruled out and if long-term medical treatment failed. Data from
      this group were analyzed retrospectively. RESULTS: Multiple sinonasal anomalies
      were noted by endoscopy and sinus computed tomographic scans in the 66 patients
      in the study. These included nasal septum deviation in 46 (69.7%), concha
      bullosum in 33 (48.5%), and Haller cell in 11 (16.7%). Thirty of the patients
      with nasal septum deviation needed surgical intervention. Fifty-four (81.8%) of
      the 66 patients in the study showed significant improvement after surgery and did
      not require further medical therapy. CONCLUSIONS: Our experience demonstrates
      that non-sinusitis-related rhinogenous headache can be significantly minimized
      with surgical management, as long as a precise identification of the etiologic
      anatomical factor can be made.

PMID- 18722890
TI  - Botulinum toxin therapy: a tempting tool in the management of salivary secretory
      disorders.
AB  - PURPOSE: The aim of the study was to investigate the feasibility and
      effectiveness of botulinum toxin therapy in salivary secretory disorders.
      MATERIALS AND METHODS: We treated 24 patients with botulinum neurotoxin type A
      for drooling, salivary fistulas, sialoceles, recurrent parotitis, and Frey's
      syndrome; each parotid gland and submandibular gland received 25 to 60 and 10 to
      40 mouse units, respectively, per session. All the patients other than those with
      Frey's syndrome underwent, for diagnostic purpose, color Doppler ultrasonography
      (Hitachi H 21; frequency, 7.5 MHz, Scanner, Kashiwa, Japan), and Minor's test was
      carried out for gustatory sweating; pretreatment magnetic resonance sialography
      (Philips Gyroscan Intera, Eindhoven, The Netherlands) and sialoendoscopy were
      also performed in selected cases. The follow-up included clinical and
      ultrasonographic examinations and Minor's test. RESULTS: A clinical improvement
      was observed in all patients: complete clinical recovery in 12, subtotal in 6,
      and partial in 6. A self-assessment test suggested the cessation of sweating by
      the 10th day in most patients with Frey's syndrome. Botulinum toxin lost its
      effectiveness approximately after 4 months, requiring further administrations
      especially for drooling. No major side effects were observed with the exception
      of transitory paresis of the lower branch of the facial nerve in a patient with
      concomitant autonomic diabetic neuropathy. CONCLUSIONS: Our findings suggest that
      botulinum toxin therapy is valid for the nonsurgical management of patients with
      salivary secretory disorders; the use of color Doppler ultrasonographic
      monitoring warrants the safety of the procedure.

PMID- 18722891
TI  - Experimental otoacoustic emission and auditory brainstem response changes by
      stellate ganglion blockage in rat.
AB  - INTRODUCTION: To investigate the effect of stellate ganglion (SG) block on
      hearing in rats. MATERIALS AND METHODS: Sixteen male adult rats were randomly
      divided into 2 equal groups. Both groups underwent preblock auditory brainstem
      responses (ABRs) in response to tone bursts at 4, 6, and 8 kHz and otoacoustic
      emissions in response to distortion products as a function of f2 frequency at 1,
      2, 4, and 6 kHz. Local anesthetic (0.2 mL of 2% prilokain) was administered to
      the left SG of the study group by posterior cervical percutaneous approach for
      cervical sympathetic blockage. In the control group, 0.2 mL of physiological
      saline was injected to the left SG. Postblock hearing evaluations were made after
      15 minutes of injections. RESULTS: Both Dp-gram and I/O function records
      suggested that whereas hearing thresholds were not affected in lower frequencies
      after SG blockage, it tended to increase at higher frequencies. In ABR records,
      waves I and II showed marked latency shift across all frequencies. The interpeak
      latency of waves I and II was shortened after blockage. Saline injection did not
      show any significant ABR or distortion-product otoacoustic emission threshold
      shift across frequencies at 60, 70, 80, and 90 dB sound pressure level.
      CONCLUSION: Our data demonstrate that SG block improved the hearing parameters in
      rats with normal cochlear blood flow. To recommend SG blockage as a treatment
      option in the vascular pathologies of cochlea, further investigation should
      assess the efficiency of ganglion blockage in hearing parameters of rats with
      impaired cochlear blood flow.

PMID- 18722892
TI  - An otolaryngologist's experience with in-flight commercial airline medical
      emergencies: three case reports and literature review.
AB  - Managing a medical emergency onboard a commercial airline is an uncommon but real
      possibility for those physicians who fly. Understanding your potential role,
      management options, medical supplies and help that is available to you is
      important.

PMID- 18722893
TI  - Carcinoid tumor of the middle ear: report of a case.
AB  - Carcinoid tumor of the middle ear is an extremely rare lesion of the middle ear,
      and thus its diagnosis is frequently delayed. Some authors found it hard to
      differentiate middle ear carcinoid from the middle ear adenoma. However, the
      balance of opinion is currently on the side of considering it as a separate
      clinical entity. Definitive diagnosis is made by identifying neurosecretory tumor
      cells using immunohistochemistry and electron microscopy. It usually follows a
      nonaggressive clinical course, rarely metastases, and infrequently recurs after
      radical excisions. We present a patient with middle ear carcinoid, who is free of
      disease 2 years after the resection of the tumor mass with canal wall-down
      procedure. The relevant literature is also herewith reviewed.

PMID- 18722894
TI  - Peripheral ameloblastoma of the maxilla: a case report and literature review.
AB  - Peripheral ameloblastoma is a rare, benign, extraosseous neoplasm of the
      odontogenic epithelium. We report a case of peripheral ameloblastoma, detail our
      surgical therapy and review important elements in the pathological diagnosis and
      treatment of this unusual neoplasm.

PMID- 18722895
TI  - Iatrogenic ear lobule ischemic injury from pressure dressing as an unusual
      complication of parotidectomy.
AB  - The use of compressive dressing is usually spread to enhance neovascularization
      of the dissected facial flap by elimination of dead space between the flap and
      the dermis in parotid surgery through facelift incision. The author reports a
      clinical case of compressive dressing after parotidectomy that was
      inappropriately performed to folding of the ear lobule, leading to ischemic
      injury. This iatrogenic complication resulted in the development of contracture
      of ear lobule and deformity of auricle. Consequently, careful compressive
      dressing after parotidectomy through facelift incision must be applied; and the
      wound must be inspected daily for early detection and prompt treatment of local
      complications.

PMID- 18722898
TI  - Surgical reconstruction of the high-risk patient. Preface.

PMID- 18722896
TI  - Left ventricular isovolumic relaxation and renin-angiotensin system in the growth
      restricted fetus.
AB  - OBJECTIVE: To determine left ventricular isovolumic relaxation time (LV IRT) in
      normally developing and growth restricted fetuses (FGR) as an indicator of fetal
      cardiac afterload and neonatal systolic blood pressure. STUDY DESIGN: A
      prospective longitudinal study in 124 normally developing and 47 growth
      restricted fetuses (FGR). LV IRT, fetal heart rate (FHR) and umbilical artery
      pulsatility index (PI) were determined at 2-3 week intervals starting at 22-26
      weeks of gestation until delivery. Renin and angiotensin I levels were measured
      by radioimmunoassay in umbilical venous blood after delivery. Systolic blood
      pressure was measured at day 1 and day 5 of postnatal life. To evaluate the
      association between LV IRT, gestational age and FHR, bivariate regression
      analyses were performed. RESULTS: Mean LV IRT (62+/-8 ms) was 29 percent longer
      in FGR as compared to the normal subset (47+/-6 ms) at all gestational ages
      (p<0.001). Mean postnatal active plasma renin level (7.78+/-S.D. 1.03 ng/ml) and
      postnatal angiotensin I level (4.21+/-0.70 ng/ml) in the FGR subset were
      significantly higher (p<0.001) than in the normal subset (4.81+/-1.04 ng/ml,
      renin and 2.69+/-0.44 ng/ml, angiotensin I). There was a significant difference
      (p<0.01) in systolic blood pressure between the two subsets on postnatal day 1
      (FGR 52+/-6 mmHg vs. normal 46+/-4 mmHg) and day 5 (FGR 76+/-5 mmHg vs. normal
      60+/-6 mmHg). CONCLUSION: Left ventricular isovolumic relaxation time may act as
      a sensitive index of increased arterial afterload in the growth retarded fetus
      and may herald raised systolic blood pressure in the early neonatal period.

PMID- 18722899
TI  - Tenotomy and tendon transfer about the forefoot, midfoot and hindfoot.
AB  - Tendon lengthening and transfer are essential surgical procedures for every foot
      and ankle surgeon to master, because they are useful in restoring balance and
      correcting flexible foot deformities. These techniques are even more useful in
      treating the high-risk patient, because they involve minimal soft-tissue injury
      and maximum preservation of vascularity. The primary goal of this article is to
      supplement the foot and ankle surgeon's options for treating static and dynamic
      foot deformities in the high-risk patient by discussing useful tendon lengthening
      and transfer procedures about the forefoot, midfoot, and hindfoot.

PMID- 18722900
TI  - Surgical correction of soft-tissue ankle equinus contracture.
AB  - Soft-tissue ankle equinus contracture is an important component of numerous foot
      and ankle deformities. In high-risk patients who have multiple co-morbidities,
      procedure selection and careful surgical technique are paramount to increase the
      likelihood of postoperative success. This article discusses the indications for
      percutaneous Achilles tendon lengthening, open gastrocnemius recession, and
      endoscopic gastrocnemius recession, and provides a detailed description of each
      surgical technique with pearls to avoid intra-perative and postoperative
      complications specific to the high-risk patient. Thorough knowledge of each of
      these techniques will aide the foot and ankle surgeon in appropriate peri
      operative management of equinus deformity in a complex patient population.

PMID- 18722901
TI  - Minimum-incision metatarsal osteotomies.
AB  - This article focuses on minimal-incision metatarsal osteotomies for treating
      ulcerative lesions related to hallux valgus deformities and central and fifth
      metatarsal plantar ulcerations to correct the structural deformity responsible
      for the ulceration. The authors presented a structured review of the literature
      regarding complications associated with the use of minimum-incision surgical
      techniques available for the first, central, and fifth metatarsals and techniques
      to avoid them. Although a steep learning curve exists with these procedures, the
      advantage of performing minimum- incision metatarsal osteotomies in high-risk
      populations allows for rapid and predictable resolution of recalcitrant or
      recurrent ulcerations through correction of the underlying structural deformity
      with minimal complications.

PMID- 18722902
TI  - Minimum-incision ray resection.
AB  - Ray resection for localized necrosis, infection, and osteomyelitis is an accepted
      procedure allowing removal of the diseased toe and metatarsal. The traditional
      approach involves a rather lengthy incision and dissection that can compromise
      the vascular supply to the remaining forefoot. The use of minimum incision
      techniques to perform metatarsal ray resection as presented here represents a
      simple, reliable, and easily reproduced procedure that limits soft-tissue
      dissection and the associated wound healing-related complications inherent to the
      traditional approach. Following minimum incision metatarsal ray resection, the
      resultant defect from the toe amputation can be primarily closed, covered with a
      split-thickness skin graft, or closed in delayed primary fashion with the use of
      a mini-external fixation device. The authors present the proper indications and a
      step-by-step guide for performing minimum incision metatarsal ray resection with
      and without the supplemental use of mini-external fixation to close the soft
      tissue defect about the toe amputation site.

PMID- 18722903
TI  - Soft-tissue and osseous techniques to balance forefoot and midfoot amputations.
AB  - Soft-tissue and osseous balancing of forefoot and midfoot amputations is
      imperative to provide the patient with a stable, durable, and functional residual
      foot. This article discusses reproducible methods for balancing transmetatarsal
      and Lisfranc amputations in high-risk patients, with detailed explanations of the
      recommended surgical techniques. In addition to performing the appropriate
      procedures for the individual patient, careful attention to the perioperative
      management of this patient population, with a multidisciplinary approach, is
      mandatory for long-term success.

PMID- 18722904
TI  - Internal pedal amputations.
AB  - Internal pedal amputation consists of resection of the metatarsals, midtarsal
      bones, or talus with preservation of the toes and soft-tissue envelope. Although
      used in the past for the treatment of tuberculosis within the pedal skeleton,
      internal pedal amputations have become almost forgotten, historical procedures.
      However, following internal pedal amputations of a diabetic patient, the foot
      undergoes significant contracture that results in a stable, functional,
      foreshortened residual foot capable of being protected in custom-molded shoe gear
      with external or in-shoe orthoses. The author presents the surgical approach and
      postoperative treatment regime for each form of internal pedal amputation, as
      well as "pearls" for success.

PMID- 18722905
TI  - Minimally invasive soft-tissue and osseous stabilization (MISOS) technique for
      midfoot and hindfoot deformities.
AB  - The surgical repair of unstable midfoot and hindfoot deformities in the high-risk
      patient remains a challenge with little guidance available in the literature. The
      author presents a proposed surgical intervention for midfoot and hindfoot
      deformities utilizing a minimally invasive soft-tissue and osseous stabilization
      (MISOS) approach. The article presents a detailed, step-by-step description of
      the procedure used for these difficult limb salvage cases.

PMID- 18722906
TI  - Corrective midfoot osteotomies.
AB  - Corrective midfoot osteotomies involve complete separation of the forefoot and
      hindfoot through the level of the midfoot, followed by uni-, bi-, or triplanar
      realignment and arthrodesis. This technique can be performed through various
      approaches; however, in the high-risk patient, percutaneous and minimum incision
      techniques are necessary to limit the potential of developing soft tissue injury.
      These master level techniques require extensive surgical experience and detailed
      knowledge of lower extremity biomechanics. The authors discuss preoperative
      clinical and radiographic evaluation, specific operative techniques used, and
      postoperative management for the high-risk patient undergoing corrective midfoot
      osteotomy.

PMID- 18722907
TI  - Percutaneous fixation of forefoot, midfoot, hindfoot, and ankle fracture
      dislocations.
AB  - Open reduction with rigid internal fixation is the basic principle for surgical
      management in foot and ankle trauma. High-risk patients present a surgical
      dilemma for the foot and ankle surgeon because the possible complications are
      magnified in this patient population. Percutaneous fixation is a unique
      alternative for achieving anatomic stabilization without increased physical
      strain to the patient. The significant advantages of percutaneous fixation
      include minimizing damage to the vascular supply, maintaining and preserving a
      stable soft tissue envelope, and decreasing the potential risk for infection.
      This article provides an overview of percutaneous surgical fixation methods and
      their role in foot and ankle trauma for the high-risk patient.

PMID- 18722908
TI  - Percutaneous reduction and external fixation for foot and ankle fractures.
AB  - Percutaneous reduction with external fixation is an advanced technique for
      surgical management in foot and ankle trauma. In the high-risk patient, closed or
      percutaneous reduction followed by external fixation for reduction and
      stabilization is a unique alternative to achieve anatomic stabilization without
      increased physical strain to the patient. The significant advantages of this
      approach include minimizing damage to the vascular supply, maintaining and
      preserving a stable soft tissue envelope, and allowing for correction to be
      performed acutely or adjusted gradually over time. This article provides an
      overview of closed or percutaneous reduction with limited soft tissue dissection
      and external fixation stabilization techniques, and their role in foot and ankle
      trauma for the high-risk patient.

PMID- 18722909
TI  - Percutaneous bone marrow aspirate and bone graft harvesting techniques in the
      lower extremity.
AB  - Autogenous bone marrow aspirate and cancellous bone graft represent a useful
      adjuvant to enhance soft tissue and osseous healing in high-risk patients. The
      authors present a review of the pertinent literature and step-by-step guidelines
      for performing reliable, simple, and reproducible percutaneous surgical
      techniques to harvest autogenous bone marrow aspirate and cancellous bone graft
      from the proximal medial tibial metaphysis and lateral calcaneus. In addition,
      these techniques are associated with low morbidity and financial cost.

PMID- 18722910
TI  - Use of circular external fixation for combined subtalar joint fusion and ankle
      distraction.
AB  - The authors discuss a novel technique not previously published that incorporates
      a subtalar joint arthrodesis with an ankle joint arthrodiastasis as an
      alternative to a tibiotalocalcaneal arthrodesis. Young and active patients who
      experience refractory pain and stiffness to the rearfoot and ankle secondary to
      combined severe subtalar and ankle arthrosis are suitable candidates for this
      surgical procedure. This new approach is based on sound principles in the
      treatment of severe arthrosis affecting the ankle and subtalar joint. The authors
      are currently prospectively reviewing their surgical experience with this
      procedure and believe that it provides an alternative option for the patient,
      with potentially promising long-term results.

PMID- 18722911
TI  - Salvage of the first ray with concomitant septic and gouty arthritis by use of a
      bone block joint distraction arthrodesis and external fixation.
AB  - Gouty arthropathy about the first metatarsal-phalangeal joint with a superimposed
      deep infection poses a great challenge to the foot and ankle surgeon. The
      inflammatory nature of gout compromises the soft-tissue envelope and vasculature
      to the area. Acute gouty arthropathy is usually a contraindication to surgical
      intervention secondary to wound-healing complications and possible vasospasm
      leading to tissue necrosis. However, if deep infection is present this must be
      managed with adequate surgical debridement followed by delayed soft-tissue and
      osseous reconstruction to prevent amputation. The authors present an exceptional
      clinical manifestation of gouty arthropathy of the first metatarsal-phalangeal
      joint concomitant with deep abscess and osteomyelitis and the surgical approach
      taken to afford functional limb salvage.

PMID- 18722912
TI  - Foreword. Regional chemotherapy for cancer inclusive of perfusion and infusion
      techniques.

PMID- 18722913
TI  - Preface. The evolution of regional therapy modalities.

PMID- 18722914
TI  - Regional chemotherapy: overview.
AB  - Regional chemotherapy was developed in the 1950s and continues to play an
      integral part in the development of newer therapies for advanced solid
      malignancies. Regional therapies have evolved in complexity but are still based
      on the pharmacokinetics of drug delivery to solid malignancies. Newer techniques
      demonstrate that the combination of regional therapies, hyperthermia, and surgery
      is essential in promoting improved patient outcomes.

PMID- 18722915
TI  - Current clinical and research approaches to optimizing regional chemotherapy:
      novel strategies generated through a better understanding of drug
      pharmacokinetics, drug resistance, and the development of clinically relevant
      animal models.
AB  - A common treatment modality for in transit melanoma of the extremity has been
      hyperthermic isolated limb perfusion (HILP) with melphalan and more recently,
      isolated limb infusion (ILI) with melphalan with or without dactinomycin.
      Research in the area has primarily focused on maximizing drug delivery through a
      better understanding of pharmacokinetics while maintaining acceptable levels of
      toxicity. Although other agents continue to be explored as regional chemotherapy
      agents, melphalan is currently the drug of choice, although temozolomide has
      demonstrated promising preclinical results. Resistance mechanisms to melphalan
      and melphalan pharmacokinetics are studied using animal models of HILP and ILI.
      The addition of modulators to overcome resistance to the traditional chemotherapy
      regimen may ultimately improve the clinical response in patients with in-transit
      melanoma of the extremity.

PMID- 18722916
TI  - Regional chemotherapy: a focus on hepatic artery infusion for colorectal cancer
      liver metastases.
AB  - Regional infusion strategies have been used as a treatment modality in multiple
      cancers, including ovarian, appendiceal, and colorectal cancers. Perhaps the most
      illustrative use of regional therapy is that of hepatic arterial infusion (HAI)
      for liver metastases from colorectal cancer. The administration of chemotherapy
      by HAI is logical and has theoretic advantages over systemic chemotherapy for the
      treatment of hepatic metastases from colorectal cancer. With the use of an
      appropriately chosen chemotherapy agent, HAI can generate an increase in hepatic
      tumor drug exposure as compared with intravenous delivery of the same agent. This
      article reviews the pharmacologic benefits of HAI therapy and the contemporary
      trials performed and underway.

PMID- 18722917
TI  - Clinical pharmacokinetics of isolated pelvic perfusion.
AB  - The pharmacokinetic results of this study indicate that there is significant
      enhancement of pelvic drug levels with isolated pelvic perfusion, with the
      potential of increasing the therapeutic index and clinical efficacy. This system
      would seem to be ideal for evaluating fast-acting and highly toxic experimental
      drugs on human pelvic cancers having treatment protocols of limited clinical
      success. Pharmacokinetic modeling using empiric approximations for the kinetic
      rate constants is a convenient and novel way of fitting data using relatively
      simple mathematics and commercially available spreadsheets.

PMID- 18722918
TI  - Isolated limb perfusion for melanoma.
AB  - Isolated limb perfusion with high-dose chemotherapy is an accepted treatment
      modality to achieve locoregional control in advanced melanoma of the extremities.
      The drug of choice is melphalan. Tumor necrosis factor-alpha is frequently added
      to melphalan in bulky disease, and this combination may be an option for repeat
      perfusion for recurrent melanoma after a first perfusion. Results of perfusions
      performed with tissue temperatures between 37 degrees C and 38 degrees C seem to
      be equivalent to those of the perfusions performed under mild hyperthermic
      conditions. Perfusion cannot be recommended as an adjunct to wide local excision
      in patients who have primary melanoma. Adjuvant perfusion in repeatedly recurrent
      limb melanoma, however, may be of value because it lengthens the limb recurrence
      free interval and decreases the number of lesions per recurrence significantly.
      Regional toxicity of perfusion should be mild when risk factors are taken into
      account.

PMID- 18722919
TI  - Pharmacokinetics of regional therapy: isolated limb infusion and other low flow
      techniques for extremity melanoma.
AB  - Isolated limb infusion (ILI) provides a simple, minimally invasive, and yet
      effective method of delivering high doses of cytotoxic drugs into tumor tissue
      with minimal systemic side effects because there is no significant drug leakage
      into the systemic circulation. The ILI technique is a technically less complex
      procedure than conventional ILP that can be used in patients who have advanced or
      persistently recurrent disease in an extremity. It is an attractive palliative
      option because it preserves limb function and maintains quality of life. Repeat
      ILI is safe and effective. Because the risk for systemic leakage is extremely
      low, ILI provides an excellent model in which to test new drugs and drug
      combinations.

PMID- 18722920
TI  - Extremity perfusion for sarcoma.
AB  - For more than 50 years, the technique of extremity perfusion has been explored in
      the limb salvage treatment of local, recurrent, and multifocal sarcomas. The
      "discovery" of tumor necrosis factor-alpha in combination with melphalan was a
      real breakthrough in the treatment of primarily irresectable extremity sarcomas.
      Development of new treatment strategies in extremity perfusion, better perfusion
      or infusion equipment, and modifying the technique and the use of molecular
      imaging technology might further improve limb salvage rates and decrease local
      failures in the future and provide more insight into the tumor biology of
      sarcoma.

PMID- 18722921
TI  - Pelvic perfusion for advanced colorectal cancers.
AB  - Isolated pelvic perfusion (IPP) is a form of intra-arterial local-regional
      treatment of tumor-bearing organs. IPP using a simplified balloon occlusion
      technique has shown promise in palliation of resectability of advanced rectal
      cancer in patients not amenable to treatment with conventional chemoradiation.
      This article reviews technique criteria and the response to IPP from seven
      literature studies of isolated pelvic perfusion with colorectal cancer. Current
      efforts should be directed to improving anti-tumor responses by optimizing
      chemotherapeutic protocols and modifying perfusion parameters, so that hopefully,
      this will lead to a more standardized and improved procedure for the isolated
      pelvic perfusion technique.

PMID- 18722922
TI  - Percutaneous pelvic perfusion with extracorporeal chemofiltration for advanced
      uterine cervical carcinoma.
AB  - This review was focused on a new intra-arterial infusion system with an
      extracorporeal chemofiltration circuit. After inferior vena cava isolation was
      percutaneously achieved by balloon catheter technique, cisplatin (140-240
      mg/m(2)) was administered by intrauterine arterial infusion, with inferior and
      superior gluteal arterial embolization. The platinum-containing blood was pumped
      through an extracorporeal charcoal chemofiltration circuit. The percutaneous
      pelvic perfusion with extracorporeal chemofiltration (PPPEC) achieved a super
      high-dose cisplatin perfusion with the minimal adverse effects, allowing
      cisplatin dose escalation with further augmented tumor response. The results
      obtained in 23 patients who received neoadjuvant chemotherapy under PPPEC
      demonstrate that PPPEC has a better therapeutic advantage because of prompt tumor
      down-staging of locally advanced uterine cervical carcinoma with minimal adverse
      effects.

PMID- 18722923
TI  - Development of isolated hepatic perfusion for patients who have unresectable
      hepatic malignancies.
AB  - Isolated hepatic perfusion (IHP) has a role in the treatment of colorectal
      carcinoma, ocular melanoma, and neuroendocrine tumor liver metastases. Outcomes
      data with IHP have improved with better patient selection, adoption of standard
      operative techniques, use of appropriate types and doses of chemotherapeutics,
      and careful measures of efficacy and survival. The percutaneous approach to IHP,
      the treatment of additional tumor types (eg, unresectable hepatocellular
      carcinoma, gastrointestinal sarcoma, occult primaries), the use of other agents
      within the IHP circuit, and gene therapy all deserve additional attention.

PMID- 18722924
TI  - Isolated hepatic perfusion for the treatment of liver tumors: sunset or sunrise?
AB  - Experience with isolated hepatic perfusion (IHP) is limited to a few centers in
      the world because of the technical difficulties, surgery-related morbidity, and
      unproved efficacy in randomized trials. Experimental animal IHP models have led
      to exploring new ways of improving efficacy, reducing technical difficulties, and
      minimizing regional and systemic toxicity. Future research should be directed to
      the identification of suitable biologic or chemotherapeutic agents, defining
      clinical indications, and development of technical modifications to make it more
      generally applicable and even repeatable.

PMID- 18722925
TI  - Regional chemotherapy for carcinoma of the lung.
AB  - The potential benefit of regional chemotherapy is to reach high local drug
      concentrations in the treated area by reducing systemic side effects. Today,
      different application forms are available, such as intra-arterial infusion,
      sometimes in form of chemoembolization; intracavitary application techniques,
      such as intrapleural infusion or intraperitoneal perfusion; and isolated
      perfusion techniques, such as extremity perfusion or pelvic stop-flow perfusions.
      Up to now, only a few of these techniques have reached a level of standardization
      combined with an efficacy superior to conventional systemic chemotherapy to be
      accepted as a standard treatment by the oncologic community. This article will
      deal with the problems of regional chemotherapy for the treatment of carcinoma of
      the lung.

PMID- 18722926
TI  - Intra-arterial chemotherapy for head and neck cancer: experiences from three
      continents.
AB  - Intra-arterial infusion of chemotherapy agents for cancer of the head and neck
      has been used for several decades. This article provides the rationale,
      historical background, and current state of investigations for patients treated
      in this manner. The experience with this route of drug delivery comes from three
      geographic regions: Europe, Japan, and North America. While the results of the
      trials have yet to establish the approach as being superior to intravenous
      infusions, continued research is warranted.

PMID- 18722927
TI  - Locoregional treatment of malignant hepatic tumors with biologic response
      modifiers.
AB  - Locoregional delivery of biologic response modifiers (BRMs) to hepatic tumors is
      an appealing approach to increase the dwell time of BMRs, to minimize the
      systemic toxicity, and to induce local and possibly systemic immune responses
      against tumor cells. Previous clinical studies using this approach showed some
      encouraging results. However, a large-scale clinical trial is needed to prove the
      efficacy of locoregional BMR treatment in primary and metastatic hepatic tumors.
      Combination of various BRM agents with appropriate treatment modalities might
      further improve the efficacy of locoregional BMR treatment. Additionally, we need
      to collect more information regarding the host immune response and change in
      tumor microenvironment after delivering BMRs to hepatic tumors.

PMID- 18722928
TI  - Regional infusion-radioembolization.
AB  - Selective internal radiation therapy involves the intra-arterial delivery of
      radioactive beads to the tumor while minimizing dosing to the adjacent organ.
      Because this technique invariably results in some degree of embolization, it has
      also been termed radioembolization. More than 8000 patients have been treated
      worldwide, with a large body of experience with primary hepatocellular carcinoma
      (HCC) and metastatic colorectal carcinoma (MCRC) and growing experience with
      other tumors (metastatic neuroendocrine, breast carcinoma, cholangiocarcinoma).
      Response rates by FDG-PET are 80% to 90%. Complications are uncommon and most
      often consist of self-limited malaise. More significant complications, including
      radiation-induced liver disease, ischemic cholecystitis, and gastrointestinal
      ulceration may be seen in up to 10% of patients. This underscores the critical
      importance of patient selection and meticulous technique. Median survival times
      in patients who have HCC and MCRC are significantly improved compared with
      historic controls. Further study is required to determine the appropriate role of
      radioembolization in the context of state-of-the-art chemotherapy and other liver
      directed therapies.

PMID- 18722929
TI  - Bedside echocardiographic assessment for trauma/critical care: the BEAT exam.

PMID- 18722933
TI  - Enhancing participation of older women in surgical trials.
AB  - BACKGROUND: Older participants are often excluded from clinical trials,
      precluding a representative sample. STUDY DESIGN: Using qualitative and
      quantitative methods, we examined recruitment and retention of older women with
      pelvic organ prolapse in two surgical trials: the randomized Colpopexy And
      Urinary Reduction Efforts (CARE) study and the Longitudinal Pelvic Symptoms and
      Patient Satisfaction After Colpocleisis cohort study. Using focus groups, we
      developed a questionnaire addressing factors facilitating and impeding the
      recruitment and retention of older study participants and administered it to
      research staff. Enrollment-to-surgery ratios, missed visit rates, and dropout
      rates for older and younger participants were compared using Fisher's exact test,
      with cut-points of 70 and 80 years for the CARE and Colpocleisis studies,
      respectively. RESULTS: Questionnaires were completed by 23 physician
      investigators and 11 nurses or coordinators (92% response rate). Respondents
      indicated it was more difficult to recruit older research participants (32%),
      obtain informed consent (56%), and retain participants to study completion (50%).
      Challenges to recruitment included caregiver involvement in the decision to
      participate and participant comorbidities. Perceived barriers to retention were
      transportation, caregiver availability, and participant fatigue. Data quality was
      challenged by sensory and cognitive impairment, resulting in a change from
      telephone interviews to in-person visits in the Colpocleisis study. Older
      participants did not have higher dropout rates than younger participants. There
      were no differences in missed in-person visits or telephone interview rates
      between age groups. CONCLUSIONS: Strategies, albeit unstudied, could assist
      investigators in planning surgical trials that successfully enroll and retain
      older women.

PMID- 18722934
TI  - Racial disparity in surgical mortality after major hepatectomy.
AB  - BACKGROUND: The relationship between surgical mortality and race has not been
      studied for major hepatectomy. We sought to quantify and explore the nature of
      racial disparities in surgical mortality after major hepatectomy in a nationally
      representative cohort of patients. STUDY DESIGN: We conducted a retrospective
      cohort study using data from the Nationwide Inpatient Sample (1998 to 2005).
      Adult patients undergoing major hepatectomy within 1 day of nontrauma admission
      were included. Logistic regression models were used to assess the variation of in
      hospital mortality by race after adjustment for other risk factors. RESULTS: The
      study cohort consisted of 3,552 observations representing 17,794 patients
      undergoing major hepatectomy. Unadjusted analyses revealed that African-American
      patients had a two-fold increased odds of surgical mortality (odds ratio 2.22,
      95% CI 1.38 to 3.57) relative to Caucasians. Even after adjustment for other risk
      factors, African Americans had a two-fold increased odds of surgical mortality
      (odds ratio 2.15, 95% CI 1.28 to 3.61) relative to Caucasians. Stratified
      analyses restricting the cohort to patients without comorbidities, those with
      neoplasms, those with private insurance, or those treated at high-volume
      hospitals all demonstrated racial disparities in surgical mortality. CONCLUSIONS:
      In-hospital mortality after major hepatectomy varies substantially by race. After
      adjustment for potential confounders, African-American patients have two-fold
      higher population-level odds of surgical mortality than Caucasian patients do.
      Our analyses suggest that clinical factors, insurance status, and hospital
      factors do not account for these differences. Additional studies to clarify the
      nature of this disparity and identify targets for intervention are warranted.

PMID- 18722935
TI  - Rapid-response, molecular-friendly surgical pathology: a radical departure from
      the century-old routine practice.
AB  - BACKGROUND: Currently, surgeons have to wait for at least 1 day to receive the
      pathology report of a biopsy or other surgical excision. This delay is mandated
      by the overnight tissue-processing methods that have been in use for more than a
      century. Patient anxiety and delay in treatment are consequences of this
      practice. Here we report the impact of a tissue-processing system on the
      turnaround time of surgical pathology reporting and its potential effect on
      overall patient management. This technique provides the feasibility for
      performing molecular assays on the same sample used for pathologic diagnosis.
      STUDY DESIGN: Biopsies and other surgically removed specimens from patients
      treated at the University of Miami, Jackson Memorial Hospital during calendar
      year 2005 were processed by an automated, microwave-assisted rapid tissue
      processing method. Turnaround time for surgical pathology reports was calculated
      and compared with that of year 1996, the last year before the new technology was
      phased in. RESULTS: Total tissue-processing time was reduced from 8 to 10 hours
      to 67 minutes, resulting in the availability of slides in less than 3 hours. In
      80% of the patients, diagnoses were reported on the same day they were received
      in the laboratory. The 1-day turnaround for the reports in 1996 was < 1%.
      Histology of rapidly processed tissues and their histochemical and
      immunohistochemical properties were comparable with those of the traditionally
      prepared material. CONCLUSIONS: The rapid turnaround capability of the new tissue
      processing system has allowed the pathology laboratory to render the final report
      in the majority of specimens on the day they are received. The feasibility of
      preserving macromolecules in the same clinical samples used for diagnosis is a
      timely advantage in the era of molecular medicine.

PMID- 18722936
TI  - Risk factors for surgical site infection after major breast operation.
AB  - BACKGROUND: Understanding surgical site infection (SSI) risk factors after breast
      operation is essential to develop infection-prevention strategies and improve
      surgical outcomes. METHODS: We performed a retrospective case-control study with
      subjects selected from a cohort of mastectomy, breast reconstruction, and
      reduction surgical patients between January 1998 and June 2002 at a university
      affiliated hospital. SSI cases within 1 year after operation were identified
      using ICD-9-CM diagnosis codes for wound infection and complication or positive
      wound cultures, or both. Medical records of 57 patients with breast SSI and 268
      randomly selected uninfected control patients were reviewed. Multivariate
      logistic regression was used to identify independent risk factors for SSI.
      RESULTS: Significant independent risk factors for breast incisional SSI included
      insertion of a breast implant or tissue expander (odds ratio [OR] = 5.3; 95% CI,
      2.5 to 11.1), suboptimal prophylactic antibiotic dosing (OR = 5.1; 95% CI, 2.5 to
      10.2), transfusion (OR = 3.4; 95% CI, 1.3 to 9.0), mastectomy (OR = 3.3; 95% CI,
      1.4 to 7.7), previous chest irradiation (OR = 2.8; 95% CI, 1.2 to 6.5), and
      current or recent smoking (OR = 2.1; 95% CI, 0.9 to 4.9). Local infiltration of
      an anesthetic agent was associated with substantially reduced odds of SSI (OR =
      0.4; 95% CI, 0.1 to 0.9). CONCLUSIONS: Suboptimal prophylactic antibiotic dosing
      is a potentially modifiable risk factor for SSI after breast operation. SSI risk
      was increased in patients undergoing mastectomy and in patients who had an
      implant or tissue expander placed during operation. This information can be used
      to develop a specific risk stratification index to predict SSI and infection
      preventive strategies tailored for breast surgery patients.

PMID- 18722937
TI  - Implementation of evidence-based practices for surgical site infection
      prophylaxis: results of a pre- and postintervention study.
AB  - BACKGROUND: Although evidence-based guidelines for best practices pertaining to
      surgical site infection (SSI) prophylaxis exist, the feasibility of implementing
      such practices remains to be demonstrated outside of a controlled clinical trial.
      This study was designed to assess the safety and feasibility of implementing
      evidence-based care practices to prevent SSIs. STUDY DESIGN: A prospective,
      double-cohort (pre- and postintervention) trial in elective, general surgery
      patients was conducted. All patients undergoing elective, major colorectal or
      hepatobiliary operations were enrolled. Postintervention cohort patients were
      exposed to new strategies to improve antibiotic administration times,
      perioperative normothermia rates, and perioperative glucose control. They were
      compared with the preintervention cohort, which received standard practice at the
      time. Outcomes evaluated include timing of antibiotic administration,
      perioperative temperatures, and postoperative glucose levels. SSI rates between
      cohorts were also compared. RESULTS: A total of 208 patients were enrolled. The
      proportion of patients receiving their preoperative antibiotics within 60 minutes
      improved from 5.9% to 92.6% (p < 0.001); perioperative normothermia rates
      improved from 60.5% to 97.6% (p < 0.001) between cohorts. There was no
      improvement in rates of hyperglycemia. SSI rates improved but did not reach
      statistical significance (14.3% versus 8.7%; p = 0.21). CONCLUSIONS:
      Implementation of evidence-based care practices to prevent SSI is both safe and
      practical outside the setting of a randomized, controlled trial. Sustained
      compliance remains to be demonstrated, although practice audits at our
      institution suggest ongoing success is possible.

PMID- 18722938
TI  - Outcomes of multiple wire localization for larger breast cancers: when can
      mastectomy be avoided?
AB  - BACKGROUND: Mastectomy is often recommended when mammography shows a breast
      cancer with extensive calcifications. We wished to determine whether the use of
      multiple localizing wires to guide lumpectomy in this setting was associated with
      increased rates of breast conservation. We also wanted to identify factors that
      predicted a poor chance of successful lumpectomy, to avoid multiple lumpectomy
      attempts in a patient who would ultimately require mastectomy. STUDY DESIGN:
      Records of 153 women with breast cancer who underwent lumpectomy for larger
      lesions that required multiple wire localization and 196 controls who required
      only single wire localization were reviewed retrospectively. The number of
      localizing wires, specimen volume, largest specimen dimension, number of surgical
      procedures, and rates of breast conservation were scored. RESULTS: Seventy-seven
      percent of patients requiring multiple wire localization had successful breast
      conservation, compared with 90% of those needing only single wire localization.
      Only 28% of multiple wire patients required more than 1 excision to achieve clear
      margins, compared with 36% of single wire patients (p < 0.01). CONCLUSIONS:
      Breast conservation is possible in the great majority of breast cancer patients
      whose mammographic lesions require multiple localizing wires for excision. The
      use of multiple wires can decrease the number of procedures required to obtain
      clear lumpectomy margins.

PMID- 18722939
TI  - Ranking hospitals on surgical quality: does risk-adjustment always matter?
AB  - BACKGROUND: It is a widely held belief that detailed risk-adjustment is always
      necessary in comparative reports of surgical performance. We sought to evaluate
      the importance of risk-adjustment for two cardiac surgery report cards in New
      York and Pennsylvania. STUDY DESIGN: We abstracted data directly from publicly
      available cardiac surgery report cards from New York State (2001 and 2002) and
      Pennsylvania (2000 and 2002). We first estimated the correlation between
      unadjusted and risk-adjusted mortality rates. We then divided hospitals into
      three groups of historic performance (best, average, and worst) for both
      unadjusted and risk-adjusted mortality rankings. We then calculated the risk
      adjusted mortality within each of these groups using data from the report card
      from the subsequent year. RESULTS: Risk-adjusted and unadjusted mortality rates
      were highly correlated for both New York (Pearson's r=0.95; Spearman's r=0.91)
      and Pennsylvania (Pearson's r=0.87; Spearman's r=0.89). For both states, risk
      adjusted and unadjusted rankings were equally good at predicting subsequent
      mortality. In New York State, mortality for hospitals in the worst group was 50%
      higher than that in the best group regardless of whether unadjusted (relative
      risk [RR], 1.51) or adjusted (RR, 1.49) rankings were used. The same was found in
      Pennsylvania, where the results for unadjusted (RR, 1.53) and adjusted (RR, 1.45)
      rankings were nearly identical. CONCLUSIONS: Based on data from two prominent
      state registries, risk-adjusted and unadjusted mortality rates provide nearly
      identical estimates of hospital performance with coronary artery bypass. Risk
      adjustment may not always be important for identifying high quality hospitals.

PMID- 18722941
TI  - Longterm results of a prospective study of 225 femoral hernia repairs:
      indications for tissue and mesh repair.
AB  - BACKGROUND: Femoral hernias are uncommon, and there are relatively few clinical
      studies of longterm outcomes after repair. Although the McVay repair has been
      classically described, the infrainguinal plug technique has gained popularity in
      recent years. Evidence supporting these repairs is sparse. STUDY DESIGN: A
      prospective study of elective femoral hernia repairs was done at the Shouldice
      Hospital from June 1999 until June 2003. The tissue-based complete groin repair
      (CGR) and a preperitoneal mesh repair were performed for specific indications.
      Patients were followed annually for 5 years to examine for recurrences and
      complications. RESULTS: Two hundred fifty-six patients were enrolled, with 225
      completing 5 years of followup. Median age was 55 years, and hernias on the right
      side were more common (63.1%). Concurrent inguinal hernias were found in 115
      patients (51%), and 41 (18.2%) had a previous inguinal hernia repair. A complete
      groin repair was performed in 120 patients and a preperitoneal mesh repair in 78.
      The remaining had an infrainguinal mesh repair. The overall recurrence rate was
      3.1%, with a median time to recurrence of 12 months. There was no significant
      difference between mesh and suture repairs. Chronic postoperative pain was
      experienced by 20 patients (8.9%). CONCLUSIONS: Femoral hernias can be repaired
      electively with a tissue-based or a preperitoneal mesh technique, with durable
      longterm results. Mesh repair is indicated for recurrent femoral hernias,
      inguinofemoral hernias, prevascular hernias, association with concurrent direct
      hernias, and, if tension is anticipated, with complete groin repair.
      Infrainguinal mesh repair is used only when there has been a successful previous
      inguinal hernia repair.

PMID- 18722940
TI  - Change in use of allogeneic red blood cell transfusions among surgical patients.
AB  - BACKGROUND: Although RBC transfusions can be lifesaving, recent evidence suggests
      that their use is associated with added morbidity and mortality and that a lower
      transfusion threshold is safe. It is unclear if this new evidence has translated
      into decreased RBC use among surgical patients. The purpose of this study is to
      measure the change in use of RBCs during the last decade. STUDY DESIGN: We
      performed a cross-sectional cohort study of all patients who underwent inpatient
      operations in the 52 hospitals in Maryland in 1997 to 1998 and 2004 to 2005. The
      primary outcomes variable was whether or not the patient received an allogeneic
      RBC transfusion. We controlled for confounders related to RBC transfusion,
      including age, gender, race, type of admission, comorbid conditions, and surgeon
      patient-volume. RESULTS: Patients receiving RBCs were older (63 versus 52 years),
      were more likely to be admitted through the emergency department (37% versus 24%)
      or as a readmission (12% versus 6.9%), had more Romano-Charlson index
      comorbidities, and had a higher unadjusted mortality (6.5% versus 1.1%).
      Comparing 1997 to 1998 to 2004 to 2005, RBC use in surgical patients increased
      (8.9% versus 14%), although unadjusted mortality decreased (2.0% versus 1.5%).
      Factors associated with higher adjusted relative risk (RR) of transfusion include
      age older than 65 years (RR = 2.45), unscheduled admissions (emergency department
      RR = 1.32, readmission RR = 1.62), Romano-Charlson comorbidities (RR = 1.04 to
      2.71), third quartile of surgeon volume (RR = 1.10), death (RR = 1.24), and
      having operations in 2004 to 2005 (RR = 1.42). CONCLUSIONS: Despite evidence
      supporting more restrictive use of RBC transfusions, RBC use among surgical
      patients has increased during the last decade.

PMID- 18722942
TI  - Adenosquamous carcinoma of the pancreas: a single-institution experience
      comparing resection and palliative care.
AB  - BACKGROUND: Adenosquamous carcinoma is a rare malignancy of the exocrine
      pancreas. Previous literature has reported dismal survival for these patients. We
      examined our single-institution experience with this tumor to compare survival
      for sugical resection and palliative therapy. STUDY DESIGN: Records were reviewed
      for patients with adenosquamous pancreatic cancer evaluated during the years 1985
      to 2003. Pathology specimens were reviewed. Survival was calculated by Kaplan
      Meier method and categorical variables were compared with Chi-square analysis. A
      p value < 0.05 was considered significant. RESULTS: Twenty-three patients were
      identified with adenosquamous carcinoma of the pancreas. Twelve patients
      underwent curative resection and 11 patients had either no surgery or a
      palliative bypass procedure. For the resection group the mean age was 69 years (7
      men). In the nonoperative group the mean age was 65 years (6 men). Operative
      procedures included standard pancreaticoduodenectomy (PD), 4 patients;
      pyloruspreserving PD, 3 patients; and distal pancreatectomy, 5 patients. Median
      length of stay was 13.5 days (7-30 d). Morbidity included delayed gastric
      emptying (4 patients), leak (2 patients), superficial skin infection, abscess,
      and GI bleed (1 patient each). There was no operative or inhospital mortality in
      the resection group. For R0 resection median survival was 14.4 months compared to
      8 months for R1 and 4.8 months for patients undergoing palliative therapies.
      CONCLUSIONS: The retrospective review of our single-institution experience with
      resection and palliative care for adenosquamous cancer of the pancreas has
      demonstrated a longer survival for patients that can undergo an R0 resection.
      Although this is a small series we continue to recommend resection for these
      patients.

PMID- 18722943
TI  - Surgery for gallbladder cancer: a population-based analysis.
AB  - BACKGROUND: Gallbladder cancer is an aggressive neoplasm, and resection is the
      only curative modality. Single institutional studies report an aggressive
      surgical approach improves survival. This analysis was performed to examine the
      components of surgical resection and resultant survival. STUDY DESIGN: From 1988
      to 2003, patients aged 18 to 85 years, resected of T1-3 M0 gallbladder cancer,
      were identified from the Surveillance, Epidemiology, and End Results (SEER)
      registry. Resections were classified as en bloc (cholecystectomy + at least one
      adjacent organ) or simple (cholecystectomy only); lymphadenectomy was defined as
      three or more lymph nodes assessed. RESULTS: Of the 2,835 resected patients with
      T1-T3 M0 cancer, only 8.6% underwent an en bloc resection, and 5.3% had a
      lymphadenectomy. In multivariable analysis, age, year of resection, region, and
      advanced T-stage were associated with more aggressive resection. In univariate
      analysis, improved survival was associated with en bloc resection for T1/2
      cancers, and lymphadenectomy for T2/3 cancers. In multivariable analysis, the
      following were associated with improved survival: for T1 cancers, en bloc
      resection, younger age, lower grade, and recent year of resection; for T2
      cancers, Caucasian race (versus African-American), lower grade, and node negative
      disease, with trends for en bloc resection and lymphadenectomy; and for T3
      cancers, female gender, Caucasian race (versus American Indian), lower grade,
      node negative disease, and recent year of resection, with a strong trend for
      lymphadenectomy. CONCLUSIONS: Very few patients underwent aggressive surgery. En
      bloc resection and lymphadenectomy may have stage-specific effects on survival.
      Additional studies should explore the underuse of aggressive operations, verify
      survival advantages, and define stage-specific resection strategies.

PMID- 18722944
TI  - Caval invasion by liver tumor is limited.
AB  - BACKGROUND: Successful hepatic resection with combined inferior vena cava (IVC)
      resection has been reported. The necessity of a combined IVC resection for
      hepatic malignancies that have attached to the IVC has not been fully evaluated.
      STUDY DESIGN: In this retrospective study, 162 lesions for which preoperative CT
      findings suggested attachment to the IVC were evaluated. Patient survival rates
      were examined according to type of tumor and the operative procedure. For
      adenocarcinoma lesions, several CT findings, including extent of the IVC
      circumference attached to the tumor compared with the whole IVC circumference
      (E(IVC)), were evaluated in conjunction with IVC resection. RESULTS: Among 162
      lesions, 18 adenocarcinoma lesions were resected in combination with an IVC
      resection. Histologic IVC invasion was confirmed in eight patients. None of the
      67 hepatocellular carcinoma lesions required concomitant IVC resection. Overall 5
      year survival rate of the patients who underwent concomitant liver and IVC
      resections was 33.1%. Among the adenocarcinoma lesions, the positive predictive
      factors for IVC resection were an E(IVC) value > 25% and a peaked deformity of
      the IVC wall, according to a multivariate analysis. CONCLUSIONS: Most hepatic
      malignancies attached to the IVC wall can be completely removed without IVC
      resection. E(IVC) and deformity of the IVC on CT can be useful indicators for a
      concomitant liver and IVC resection. Careful separation of the liver and IVC is a
      key point for minimizing the size of the resected IVC and to avoid unnecessary
      IVC resection.

PMID- 18722945
TI  - Conservative management of postoperative Fever in gynecologic patients undergoing
      major abdominal or vaginal operations.
AB  - BACKGROUND: To develop a standardized protocol for management of postoperative
      fever in gynecology patients to decrease unnecessary diagnostic workups and
      empiric use of antibiotics. STUDY DESIGN: A prospective analysis of postoperative
      gynecology patients identified those who experienced fever (maximum temperature
      [T(max)] > 100.4 degrees F). Patients were triaged into low- and high-risk
      groups. High-risk patients were managed independent of the protocol. High-risk
      criteria included bowel operation, preoperative infection, immunodeficiency,
      indwelling vascular access, mechanical heart valves, and intensive care unit
      admissions. Low-risk patients were treated with observation and antipyretics.
      Patients with persistent or high fever, defined as T(max) > 101 degrees F for >
      48 hours, were evaluated and treated based on physical examination findings.
      RESULTS: We evaluated 292 postoperative patients. Forty-seven percent of patients
      had a final diagnosis of malignancy. Sixty-four patients were high-risk and 33%
      of these patients experienced fever. Using the standardized protocol, 228 low
      risk patients were managed. Thirty-seven of the 228 patients (16%) had fever
      postoperatively. Nineteen patients had low-grade fever (100.4 to 101 degrees F);
      none of these patients required antibiotics. Seventeen patients had fever (101.1
      to 102 degrees F) and one patient had fever > 102 degrees F. Using the protocol,
      6 of 37 patients (16%) were treated with antibiotics for an infectious diagnosis.
      CONCLUSIONS: Although postoperative fever is common in gynecologic patients, the
      incidence of infection is low (3%). A standardized postoperative fever protocol
      in low-risk gynecology patients decreases use of empiric antibiotics without
      compromising morbidity.

PMID- 18722946
TI  - Role of anemia in traumatic brain injury.
AB  - BACKGROUND: Few studies have investigated the effects of anemia in patients with
      traumatic brain injury (TBI). The objective of this study was to examine the role
      of anemia and blood transfusion on outcomes in TBI patients. STUDY DESIGN: We
      performed a retrospective review of all blunt trauma patients with TBI admitted
      to the ICU from July 1998 to December 2005. Admission and daily ICU blood
      hemoglobin (hemoglobin) levels and blood transfusions during the first week of
      hospitalization were measured. Anemia was defined as a hemoglobin<9 g/dL
      occurring on 3 consecutive blood draws. The role of anemia and blood transfusion
      was investigated using logistic regression adjusting for factors, with p<0.2 from
      the bivariate analysis. RESULTS: During the study period, 1,150 TBI patients were
      admitted to the ICU. When both anemia and blood transfusion were included in the
      full model, blood transfusion was significantly associated with higher mortality
      (adjusted odds ratio [AOR], 2.19 [95% CI, 1.27, 3.75]; p=0.0044) and more
      complications (AOR, 3.67 [95% CI, 2.18, 6.17]; p<0.0001), but anemia was not. But
      when transfusion was not included in the full model, anemia was a significant
      risk factor for mortality (AOR, 1.59 (95% CI, 1.13, 2.24); p=0.007) and for
      complications (AOR, 1.95 [95% CI, 1.42, 2.70]; p<0.0001). CONCLUSIONS: Blood
      transfusion is associated with significantly worse outcomes in traumatic brain
      injured patients. In addition, blood transfusion is a major contributing factor
      to worse outcomes in TBI patients who are anemic. We caution against the liberal
      use of blood in TBI patients.

PMID- 18722947
TI  - Olive oil, the mediterranean diet, and cardiovascular health.

PMID- 18722948
TI  - Culdoscopy: a foundation for natural orifice surgery--past, present, and future.

PMID- 18722950
TI  - Road map for maintaining career satisfaction and balance in surgical oncology.

PMID- 18722949
TI  - Stem cell therapy in myocardial repair and remodeling.

PMID- 18722951
TI  - Geisinger's remarkable first surgeon, Dr Harold Foss.

PMID- 18722953
TI  - Leiomyoma and leiomyosarcoma arising from the round ligament of the uterus.

PMID- 18722954
TI  - Back pain from spinal tuberculosis.

PMID- 18722956
TI  - Left-sided appendicitis: Ladd's procedure revisited.

PMID- 18722958
TI  - Toothache or trigeminal neuralgia: treatment dilemmas.

PMID- 18722959
TI  - Our days in global perspective.

PMID- 18722960
TI  - Hemorrhagic complications of optic disc drusen and available treatment options.
AB  - BACKGROUND: Optic disc drusen typically are considered benign findings. However,
      optic disc drusen can manifest with hemorrhagic complications. CASE REPORT: A
      dilated fundus examination on a 27-year-old visually asymptomatic optometry
      student found a juxtapapillary hemorrhage one quarter of a disc diameter in size
      in the right eye, immediately off the superior nasal aspect of the disc.
      Bilateral disc drusen, confirmed by hyperreflectivity on ultrasonography, were
      also noted. Fluorescein angiography and optical coherence tomography were
      diagnostic only for a deep isolated intra- and subretinal hemorrhage. Neither
      diagnostic modality could confirm the presence or absence of a choroidal
      neovascular membrane. Because of the asymptomatic nature, location of the
      hemorrhage, and lack of conclusive etiology, close monitoring was recommended.
      After 4 months, 75% of the hemorrhage had reabsorbed with no visual
      complications. CONCLUSIONS: Optic disc drusen can cause ocular hemorrhages
      through several mechanisms. Although many are benign and self-limiting, it is
      important to understand available treatment modalities should vision be
      threatened.

PMID- 18722961
TI  - Additive effect of dorzolamide hydrochloride to patients taking travoprost: a
      retrospective study.
AB  - BACKGROUND: A retrospective chart review study at a Veterans Affairs hospital
      evaluated intraocular pressure change after dorzolamide hydrochloride 2% was
      administered to patients already using travoprost. A literature search found no
      other study that looked specifically at this combination of drugs. METHODS: A
      chart review of 46 patients at the Veterans Affairs Illiana Health Care System
      was performed evaluating the intraocular pressures after dorzolamide
      hydrochloride was added to travoprost. Baseline intraocular pressures were
      obtained on patients who had been on travoprost at least 4 months. Endpoint
      intraocular pressures were then obtained from the visit closest to 6 months after
      the addition of dorzolamide hydrochloride. RESULTS: An average intraocular
      pressure reduction of an additional 20.6% was observed after adding only
      dorzolamide hydrochloride to travoprost. CONCLUSIONS: This study confirmed our
      clinical observations that dorzolamide hydrochloride added to travoprost is an
      excellent and safe choice to further lower intraocular pressures.

PMID- 18722962
TI  - Recurrent corneal erosions causing bacterial keratitis.
AB  - BACKGROUND: Any etiology of epithelial defect can lead to severe bacterial
      keratitis. Patients with recurrent corneal erosions suffer repeated corneal
      epithelial defects without significant trauma and therefore are at risk of
      infectious keratitis more frequently than someone without recurrent erosions. A
      stromal infiltrate with an overlying area of epithelial defect can be challenging
      to differentiate between infectious and noninfectious inflammatory conditions. It
      is important for clinicians to appreciate the clinical findings in these cases
      and initiate aggressive treatment promptly. CASE REPORT: A 32-year-old woman
      presented with a history of anterior basement membrane dystrophy and recurrent
      corneal erosions. She had symptoms of redness, pain, foreign body sensation,
      photophobia, epiphora, and burning in her left eye that started 2 days before the
      visit to our office. Examination showed a large epithelial defect with dense
      stromal infiltrate inferiorly on the cornea that appeared white and milky with
      diffuse cellular infiltrate as well as 3+ cells in the anterior chamber.
      CONCLUSION: Laboratory results were positive for bacterial keratitis
      (Staphylococcus aureus). Infectious presentation should be considered visually
      threatening and treated immediately and aggressively. Early intervention is
      important to help avoid severe complications.

PMID- 18722963
TI  - Complex juxtapapillary capillary hemangioma: a case report.
AB  - BACKGROUND: Juxtapapillary capillary hemangiomas can occur as isolated clinical
      abnormalities or a manifestation of von Hippel-Lindau (VHL) disease. Because of
      the location of these vascular tumors on or adjacent to the optic disc, any
      therapeutic treatment option involves risk. Management typically includes close
      monitoring, with treatment initiation as the tumor progresses or when vision is
      compromised. This case report reviews this condition while highlighting the
      treatment and potential complications associated with juxtapapillary capillary
      hemangioma. CASE REPORT: A 14-year-old black male had juxtapapillary capillary
      hemangioma diagnosed during a routine eye examination. The patient complained of
      blurry vision in the right eye, and best-corrected visual acuities (BCVA) were
      20/25 O.D. and 20/20 in the left eye. At the retinologist's discretion, no
      treatment was initiated, and the patient was advised to return in 4 months for a
      dilated retinal evaluation and referred for magnetic resonance imaging (MRI) with
      contrast of the brain. The patient was lost to follow-up and presented a year
      later when vision had deteriorated to 20/400 O.D. with an associated afferent
      pupillary defect. Enlargement of the juxtapapillary capillary hemangioma with
      increased fibrovascular growth, macular exudation, and subretinal fluid was
      observed O.D. Photodynamic therapy was initiated, and the patient experienced
      treatment complications, including a vitreous hemorrhage and serous retinal
      detachment. A scleral buckling procedure, vitreoretinal surgery, and endo-laser
      photocoagulation were performed. The patient's visual acuity improved from 20/400
      to 20/60 O.D., with the development of a dense posterior subcapsular cataract,
      for which the patient had cataract extraction. Genetic testing was positive for a
      small deletion in codon 76 of the von Hippel-Lindau gene, and MRI of the brain
      was reported to be normal. Additional testing to rule out visceral organ
      involvement, including abdominal ultrasound scan, urinalysis, and blood chemistry
      were ordered, and the patient's family was also evaluated for the presence of the
      VHL gene. CONCLUSION: The clinical course of juxtapapillary capillary hemangiomas
      is highly variable, potentially leading to significant ocular complications.
      Currently, no definitive treatment guideline is available, and any therapeutic
      option involves inherent risk because of the location of these tumors. Because
      juxtapapillary capillary hemangioma may be the only manifestation of VHL disease,
      genetic and clinical screening of patients and their relatives is highly
      recommended. Early diagnosis and treatment may improve both the visual and
      systemic prognosis in patients with juxtapapillary capillary hemangiomas.

PMID- 18722964
TI  - Laser exposure incidents: pilot ocular health and aviation safety issues.
AB  - INTRODUCTION: A database of aviation reports involving laser illumination of
      flight crewmembers has been established and maintained at the Civil Aerospace
      Medical Institute. A review of recent laser illumination reports was initiated to
      investigate the significance of these events. METHODS: Reports that involved
      laser exposures of civilian aircraft in the United States were analyzed for the
      13-month period (January 1, 2004, through January 31, 2005). RESULTS: There were
      90 reported instances of laser illumination during the study period. A total of
      53 reports involved laser exposure of commercial aircraft. Lasers illuminated the
      cockpit in 41 (46%) of the incidents. Of those, 13 (32%) incidents resulted in a
      visual impairment or distraction to a pilot, including 1 incident that reportedly
      resulted in an ocular injury. Nearly 96% of these reports occurred in the last 3
      months of the study period. There were no aviation accidents in which laser light
      illumination was found to be a contributing factor. CONCLUSION: Operational
      problems have resulted from laser illumination incidents in the national airspace
      system. Eye care practitioners, to provide effective consultations to their pilot
      patients, should be familiar with the problems that can occur with laser
      exposure.

PMID- 18722965
TI  - Investigation of surgical procedures for pelvic organ prolapse-the mesh dilemma.

PMID- 18722966
TI  - Ectopic ovarian teratoma of the uterosacral ligament associated with a large
      ovarian dermoid.

PMID- 18722967
TI  - Intramyometrial uterine fat metaplasia.

PMID- 18722968
TI  - Pain relief by continuous intraperitoneal nebulization of ropivacaine during
      gynecologic laparoscopic surgery--a randomized study and review of the
      literature.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of intraperitoneal nebulization of
      ropivacaine on pain relief during and after gynecologic laparoscopic procedures
      including a review of the literature. DESIGN: Double-blinded, randomized,
      controlled, clinical trial (Canadian Task Force classification I). SETTING:
      University hospital ambulatory gynecoendoscopic department. PATIENTS: Forty
      patients (20 patients in each arm) undergoing elective gynecologic same-day
      outpatient laparoscopic surgery including unilateral/bilateral salpingo
      oophorectomy or unilateral/bilateral ovarian cystectomy. INTERVENTIONS: The study
      group received 10 mL of 1% ropivacaine and the control group received 10 mL of
      sterile water by intraperitoneal nebulization. During surgery, vital signs were
      recorded and summarized. Postoperatively patients were followed up for 24 hours
      including visual analog scale scores and analgesic use. MEASUREMENTS AND MAIN
      RESULTS: No significant differences existed between the groups during surgery and
      at the recovery department in terms of arterial blood pressure (p=.42) or heart
      rate (p=.60). Regarding postoperative analgesia, no difference existed between
      the groups in terms of morphine consumption (p=.52) or other analgesics (p=.53).
      No significant difference existed between the groups in postoperative visual
      analog scale scores including visceral, abdominal wall, and shoulder pain during
      rest and during cough at the different time frames (30, 60, and 120 minutes and 6
      and 24 hours after surgery). CONCLUSION: Our study is the first to examine the
      effects of intraperitoneal nebulization of ropivacaine throughout laparoscopic
      gynecologic procedures on patients undergoing general anesthesia. Nebulization of
      100 mg of ropivacaine under our specific regimen of anesthesia does not improve
      patients' outcome in terms of intraoperative and postoperative pain along with
      consumption of analgesics. Further research with other regimens is required.

PMID- 18722969
TI  - The influence of adenomyosis in patients laparoscopically treated for deep
      endometriosis.
AB  - STUDY OBJECTIVE: A strong association exists between adenomyosis and
      endometriosis and a common pathogenetic mechanism was proposed. The aim of this
      study was to evaluate whether and how the presence of concurrent adenomyosis can
      affect the outcome of laparoscopic excision of deep endometriosis. DESIGN: Data
      were retrospectively collected from our computerized medical records (Canadian
      Task Force classification II-3). SETTING: General hospital. INTERVENTION:
      Restrospective evaluation. PATIENTS: From January 2003 through July 2005, 40
      consecutive patients affected by concomitant endometriosis and adenomyosis were
      included in group A and another 40 affected by endometriosis only were included
      in group B. MEASUREMENTS AND MAIN RESULTS: In group A, 20 women required bowel
      surgery (17 segmental and 3 full-thickness discoid resections) versus 16 patients
      in the other group (13 segmental bowel resections with end-to-end anastomosis and
      3 discoid resections). Dysmenorrhea and dyspareunia after treatment improved
      (p<.01) in both groups, whereas dyschezia improved only in group A. The
      persistence of menometrorrhagia was more frequent in group B (p<.01). During
      follow-up, patients of group A underwent medical treatment for a longer time than
      those of group B (p<.001). Clinical detection of endometriosis recurrence was
      more frequent in patients with adenomyosis (p<.01), whereas no difference existed
      in the incidence of the recurrence detected by ultrasound. The overall number of
      pregnancies after surgery was significantly lower in the group with adenomyosis
      (p=.03). CONCLUSION: Complete excision of deep endometriosis is not always
      feasible because of adenomyosis. For this reason, preoperative imaging screening
      for adenomyosis could be included in the preoperative workup when extensive
      disease is clinically suspected.

PMID- 18722970
TI  - A phase III randomized clinical trial comparing laparoscopic or robotic radical
      hysterectomy with abdominal radical hysterectomy in patients with early stage
      cervical cancer.
AB  - STUDY OBJECTIVE: Cervical cancer is a significant health problem in countries of
      the developing world. Although case series suggest advantages of total
      laparoscopic radical hysterectomy (TLRH) compared with total abdominal radical
      hysterectomy (TARH), no randomized controlled trial is currently available to
      establish TLRH as the new standard treatment. In this study, TLRH or total
      robotic radical hysterectomy (TRRH) will be performed without a vaginally
      assisted portion of the procedure. DESIGN: A biphasic randomized controlled trial
      was designed to test feasibility of recruitment and equivalence in regard to
      disease-free survival (Canadian Task Force classification I). SETTING: Tertiary
      referral hospital. PATIENTS: Patients with histologically confirmed invasive
      squamous cell carcinoma or adenocarcinoma of the cervix, stage IA1 (with
      lymphovascular space invasion), IA2, and IB1 are eligible. INTERVENTIONS: During
      the first phase, 100 patients will be randomized (1:1) to receive either
      TLRH/TRRH or TARH, with the primary end point being the rate of enrollment.
      During the second phase, recruitment will be extended by another 640 patients in
      a 1:1 TLRH/TRRH:TARH allocation, to determine equivalence with respect to disease
      free survival with 80% power and alpha=0.05. MEASUREMENTS AND MAIN RESULTS:
      Equivalence will be assumed if the difference in disease-free survival does not
      exceed 7% at 4 years. Secondary outcomes include treatment-related morbidity,
      costs and cost effectiveness, patterns of recurrence, quality of life, pelvic
      floor function, feasibility of intraoperative sentinel node sampling, and overall
      survival. All data from this multicenter study will be entered using online
      electronic case report forms, allowing real-time assessment of data completeness
      and patient follow-up. CONCLUSION: This prospective trial aims to show the
      equivalence of a TLRH/TRRH versus TARH approach for patients with early stage
      cervical cancer following a 2-phase protocol. This trial was developed and
      designed with the input and approval of the members of the Gynecologic Oncology
      Committee from the American Association of Gynecologic Laparoscopists.

PMID- 18722971
TI  - What is the learning curve for robotic assisted gynecologic surgery?
AB  - STUDY OBJECTIVE: The purpose of this study was to estimate the learning curve
      when using the da Vinci Surgical System (Intuitive Surgical Inc., Sunnyvale, CA)
      in benign gynecologic cases by a team of 2 gynecologic laparoscopists. DESIGN:
      Retrospective case series (Canadian Task Force classification II-1). SETTING: A
      private practice obstetrics/gynecology clinic. PATIENTS: Patients requiring major
      benign gynecologic surgery who were candidates for a laparoscopic approach.
      INTERVENTION: All patients who would have otherwise been offered a transabdominal
      or conventional laparoscopic procedure were offered the option of having their
      procedure performed laparoscopically with robotic assistance. Data that were
      collected included robot set-up times by the operative room staff, operative
      times for use of robot, total operative times, and perioperative outcome. We
      analyzed the learning curve defined as the number of cases required to stabilize
      operative time to perform the various procedures. MEASUREMENTS AND MAIN RESULTS:
      One hundred thirteen patients were treated over a 22-month period with the da
      Vinci Surgical System. Most procedures were hysterectomies, whereas other
      gynecologic procedures included supracervical hysterectomy, laparoscopic vaginal
      assisted hysterectomy, myomectomy, sacrocolpopexy, and oophorectomy. Total
      operative times for hysterectomies studied sequentially stabilized at
      approximately 95 minutes after 50 cases. The decrease in robotic time did not
      depend on uterine size. The mean length of hospital stay was 24 hours, and return
      to normal activities averaged 2.8 weeks. CONCLUSIONS: Robotic assisted surgery is
      an enabling technology that allows gynecologic surgeons the ability to offer
      laparoscopic procedures to most of their patients. In the hands of surgeons with
      advanced laparoscopic skills, the learning curve to stabilize operative times for
      the various surgical procedures in women requiring benign gynecolologic
      interventions is 50 cases.

PMID- 18722972
TI  - Outpatient hysteroscopic polypectomy in postmenopausal women: a comparison
      between mechanical and electrosurgical resection.
AB  - STUDY OBJECTIVE: Comparison of operating outcomes of office hysteroscopic
      polypectomy accomplished by mechanical or bipolar electrosurgical
      instrumentation. DESIGN: Prospective study (Canadian Task Force classification II
      1). SETTING: Public hospital. PATIENTS: A total of 101 consecutive postmenopausal
      patients showing, during office hysteroscopy, 1 or more endometrial polyps
      measuring more than .5 cm. INTERVENTIONS: Hysteroscopy was carried out with a 2.9
      mm optic and a 3.9-x5.9-mm sheathed operative hysteroscope, without local
      anesthesia or systemic analgesia. The diagnostic phase was immediately followed
      by polyp resection, alternatively allocating the patients to mechanical or
      electrosurgical polypectomy. Hysteroscopic scissors were used for mechanical
      polypectomy, whereas 5F coaxial bipolar twizzle electrodes were used for
      electrosurgical polypectomy. MEASUREMENTS AND MAIN RESULTS: Effectiveness of
      polypectomy, operation time, and evaluation of induced pelvic pain (scored on a 1
      10 cm visual analog scale), were the end points of comparison between the 2
      techniques. Nine patients were excluded because of severe pelvic pain arising in
      the diagnostic phase or the finding of an oversize polyp requiring an estimated
      time of more than 30 minutes to be removed in the office setting. Of the
      remaining 92 patients, 46 underwent mechanical and 46 electrosurgical
      polypectomy. Clinical variables (i.e., age, age at menopause, parity, polyp size,
      and number) were similar in the 2 study arms. Polypectomy was accomplished in 79
      (85.8%) of 92 patients. Among the considered clinical variables, effectiveness of
      resection was significantly related to age of patients (p=.04) and polyp size
      (p=.004). Mechanical and electrosurgical polypectomy was completed in 37 (80.4%)
      of 46 patients and in 42 (91.3%) of 46 patients, respectively (p=.13).
      Furthermore, mechanical and electrosurgical resections did not significantly
      differ as regards median surgical time (15.0 min [range 5-45] and 15.5 min [range
      8-40], respectively; p=.53) and visual analog scale scores (3.7+/-2.5 and 3.2+/
      1.9, respectively; p=.48). No major complications were recorded. Atypical polyp
      histology occurred in 9 (8.8%) patients, 5 of whom were asymptomatic. CONCLUSION:
      Outpatient see-and-treat polypectomy represents a safe and effective alternative
      to resectoscopic polypectomy, leading to a complete polyp excision in about 80%
      of postmenopausal patients. No differences in the rate of polyp excision,
      surgical time, or induced pelvic discomfort were observed between electrosurgical
      and mechanical techniques.

PMID- 18722973
TI  - Receiver operating characteristic curves of symptom scores in the diagnosis of
      interstitial cystitis/painful bladder syndrome.
AB  - STUDY OBJECTIVE: Chronic pelvic pain is often a manifestation of interstitial
      cystitis (IC), for which several symptom scoring measures exist. However, the
      receiver operating characteristic (ROC) curves for these scores have not been
      described, even though such analysis could identify an optimal noninvasive test
      and suggest diagnostic test thresholds. The objective of this study was to
      develop ROC curves for IC symptom scores based on the standard of pain relief
      after cystoscopy with hydrodistention (HD). DESIGN: This is a retrospective
      analysis of IC symptom index (ICSI) and visual analog scale (VAS) bladder pain
      (VASb) scores recorded at initial patient visit. Patients underwent a diagnostic
      algorithm leading to selected HD. The ROC curves were calculated based on the
      presence of diagnostic criteria for IC found at HD (Canadian Task Force
      classification III). SETTING: A multidisciplinary chronic pelvic pain referral
      center. PATIENTS: A total of 277 women with chronic pelvic pain were evaluated.
      The mean duration of pain was 54 months; mean pelvic pain VAS score was 7.5.
      Those proved to have IC had a VASb score of 7 and an ICSI score of 11.
      INTERVENTIONS: Initial symptom score tabulation followed by a symptom-based
      diagnostic algorithm consisting of alkalinized lidocaine instillation with HD
      offered to responders. MEASUREMENTS AND MAIN RESULTS: The ROC curve for the VASb
      was shifted to the upper left compared with the ICSI, which was closer to the
      diagonal. Area under the curve was significantly greater for VASb (0.860) than
      ICSI (0.773) (p=.045). The maximum diagnostic accuracy for the ICSI was at a
      value of 14 or more (0.88) and for the VASb at a value of 7 or more (0.94).
      CONCLUSION: The most accurate symptom score for detecting IC based on this
      analysis was the VASb with a threshold of 7. Although the ICSI may have use, in
      this setting it is not as useful as the VAS for identifying patients who
      eventually prove to have IC.

PMID- 18722974
TI  - A prospective study to evaluate the anatomic and functional outcome of a
      transobturator mesh kit (prolift anterior) for symptomatic cystocele repair.
AB  - The objective of this study was to estimate the anatomical and functional outcome
      of Prolift Anterior C. All patients presenting with symptomatic stage II or
      greater anterior vaginal wall prolapse were considered to enter this prospective
      observational study. Patient characteristics and surgical parameters were
      prospectively documented. Anatomical outcome, as measured by the Pelvic Organ
      Prolapse Quantification (POP-Q) score, and functional outcome, as assessed by the
      King's College Health Questionnaire, was considered primary outcome measures.
      Complications constituted the secondary outcome measures. Fifty-one patients met
      the inclusion criteria, and 48 underwent a transobturator anterior vaginal wall
      mesh. Objective cure was realized in 46 out of 48 (95.8%) patients.
      Postoperatively, 5 out of 48 (10.4%) patients developed an erosion which required
      surgical intervention in 2 (4.3%) patients. Subjective cure was achieved in 40
      out of 42 (95.2%) patients. Urgency symptoms persisted in 3 out of 21 (14%). De
      novo urgency and frequency developed in only 1 patient. De novo stress
      incontinence developed in 4 out of 30 (13%). In 9 out of 29 (31%) of sexually
      active patients, dyspareunia due to the prolapse was present before surgery and
      disappeared in all; 3 out of 20 (15%) reported de novo dyspareunia. In
      conclusion, we state that transobturator anterior vaginal wall mesh kits provide
      a surgical tool with an acceptable but real morbidity to treat anterior vaginal
      wall prolapse with a favorable objective and subjective outcome.

PMID- 18722975
TI  - Treatment of uterine myomas with transvaginal uterine artery occlusion:
      possibilities and limitations.
AB  - The objective of this pilot study was to evaluate the feasibility of a
      transvaginal clamp prototype used for temporary uterine artery occlusion as a
      treatment for myomas. In particular, we aimed to evaluate technical aspects of
      successful occlusion with angiography and magnetic resonance imaging (MRI) and to
      evaluate possible ureter occlusion with pyelography. Ten premenopausal women aged
      34 to 37 years with menorrhagia and myomas were treated with a temporary uterine
      artery occlusion for 6 hours. Five patients did not complete the clamping
      procedure because of unsuccessful clamping. While the clamp was in position,
      angiographic examination of the uterine arteries and pyelography were performed
      in 8 of the patients. The clamps occluded both uterine arteries in 4 patients and
      1 side in another 2. Two procedures occluded the ureter unilaterally. MRI with
      contrast was done before, the day after, and 3 months after the procedure. Three
      of 5 patients who completed the clamp treatment had reduced or no contrast
      enhancement at MRI afterward. Clinical effects were obtained in 3 patients.
      Difficulties with application of the vaginal clamp were related to initial
      learning and size of the myomas. Our initial experience shows that the treatment
      is feasible in some patients with symptomatic myomas. However, improvement of the
      technique and equipment is needed. Care with regard to the ureters is required
      during further studies aimed at evaluating this approach.

PMID- 18722976
TI  - The use of narrowband imaging for identification of endometriosis.
AB  - A pilot study was designed to evaluate whether a narrowband imaging (NBI)
      endoscopic light source could detect endometriosis implants that were not
      identifiable with a visible light spectrum laparoscope. In all, 21 consecutive
      patients who were undergoing pelviscopy for pelvic pain and possible
      endometriosis were enrolled in the study. Endoscopic evaluation was performed
      using an endoscope that was fitted with a NBI light source using 415- and 540-nm
      filters. Endometriosis was first documented and photographed using visible light
      and then re-evaluated with NBI. Implants newly found with NBI were documented and
      photographed. All noted lesions were excised using a harmonic scalpel. In all, 21
      consecutive patients (age range 20-40 years) were enrolled in the study with a
      preoperative diagnosis of pelvic pain and possible pelvic endometriosis. One
      patient was excluded after evaluation with NBI did not provide additional biopsy
      specimens. Fourteen of the 20 patients had lesions identified with NBI that were
      not identified with visible light. A total of 38 biopsy specimens were taken
      using NBI; 20 (53%) of them were identified histologically as endometriosis.
      Seven patients did not have endometriosis identified with white light; however, 4
      of these patients had lesions identified with NBI that were confirmed
      endometriosis. This pilot study is a promising start in the process to evaluate
      NBI endoscopy as an effective tool for evaluating and identifying endometriosis
      implants that are not visible with white light endoscopy.

PMID- 18722977
TI  - Laparoscopic management of primary omental pregnancy.
AB  - Abdominal pregnancy is a rare and serious type of extrauterine pregnancy that is
      estimated to be approximately 1% to 4% of all ectopic pregnancies with omental
      pregnancy is the least common. An incidental case of a primary omental pregnancy
      was treated by laparoscopic partial omentectomy. The aim of this presentation is
      to keep in mind that pregnancy can exist in unusual locations, so a thorough
      inspection of the abdominal cavity is imperative.

PMID- 18722978
TI  - Urethral coitus in a patient with a microperforate hymen.
AB  - Microperforate hymen is a rare condition consisting of a tiny hymeneal orifice
      with normal female genitals. A woman had microperforate hymen in which diagnosis
      and treatment was performed after decades of urethral coitus.

PMID- 18722980
TI  - Laparoscopic resection of presacral teratomas.
AB  - Presacral and retrorectal space tumors are relatively rare lesions, the location
      of which can result in the onset of symptoms that are not well-defined.
      Retrorectal teratomas are resected to alleviate these symptoms and to rule out
      malignancy. Complete resection by one of the open abdominal or sacral approaches
      was traditionally advocated as the best treatment for either a benign or
      malignant presacral and retrorectal tumor. A 15-year-old girl had chronic,
      progressively worsening dull pelvic pain and was given the diagnosis of a
      retrorectal tumor during her first gynecologic examination. Computed tomography
      of the pelvis showed an encapsulated presacral and retrorectal tumor measuring
      10x8.5x8 cm. The retrorectal teratoma was removed by laparoscopy. No complication
      was observed interoperation. In addition, no sensory or motoric dysfunction of
      the bladder or rectum was observed postoperatively. Laparoscopy can be used to
      surgically remove presacral teratomas.

PMID- 18722979
TI  - Hand-assisted laparoscopic management of a midtrimester rudimentary horn
      pregnancy with placenta increta: a case report and literature review.
AB  - Pregnancy in a rudimentary horn is an extremely rare but serious obstetric
      condition. It is associated with uterine rupture and increased maternal
      mortality. The standard treatment is excision of the pregnancy and rudimentary
      horn. Several case reports describe a successful laparoscopic approach for
      rudimentary horn pregnancies diagnosed in the first trimester. A midtrimester
      rudimentary horn pregnancy was managed with a hand-assisted laparoscopic
      technique. This patient sought prenatal care at 19 weeks without any symptoms. A
      routine ultrasound found an empty uterus and an abdominal pregnancy was
      suggested. She subsequently had a hand-assisted laparoscopic delivery of a 19
      week fetus with excision of the left-sided noncommunicating rudimentary horn.
      Intraoperative and pathologic findings were both consistent with a
      noncommunicating uterine horn pregnancy with placenta increta. Midtrimester
      rudimentary horn pregnancy can be successfully managed via hand-assisted
      laparoscopy in a patient who is hemodynamically stable.

PMID- 18722981
TI  - A case of colouterine fistula managed laparoscopically.
AB  - Fistulas between the uterus and bowel are rarely reported. We report successful
      laparoscopic management of a colouterine fistula caused by a foreign body in the
      uterus. Fistulas between the gastrointestinal tract and the female genital tract
      are usually found between the vagina and rectum as a result of complications of
      childbirth or iatrogenic trauma. Communication between the uterus and bowel is
      rarely reported. We report successful laparoscopic management of an unusual case
      of colouterine fistula caused by a foreign body in the uterus.

PMID- 18722982
TI  - Assessment of right and left ventricular function in healthy mice by blood-pool
      pinhole gated SPECT.
AB  - The feasibility of blood-pool pinhole ECG gated SPECT was investigated in healthy
      mice to assess right and left ventricular function analysis. Anaesthetized
      (isoflurane 1-1.5%) adult CD1 mice (n=11) were analyzed after intravenous
      administration of 0.2 ml of 550 MBq of (99m)Tc human albumin. For blood-pool
      gated SPECT imaging, 48 ventral step and shoot projections with eight time bins
      per RR over 180 degrees with 64 x 64 word images were acquired with a small
      animal gamma camera equipped with a pinhole collimator of 12 cm in focal length
      and 1.5 mm in diameter. For appropriate segmentation of right and left
      ventricular volumes, a 4D Fourier analysis was performed after reconstruction and
      reorientation of blood-pool images with a voxel size of 0.55 x 0.55 x 0.55 mm(3).
      Average right and left ejection fractions were respectively 52+/-4.7% and 65+/
      5.2%. Right end diastolic and end systolic volumes were significantly higher
      compared with the corresponding left ventricular volumes (P<0.0001 each). A
      linear correlation between right and left stroke volumes (r=0.9, P<0.0001) was
      obtained and right and left cardiac outputs were not significantly different
      14.2+/-1.9 and 14.1+/-2 ml/min, respectively.

PMID- 18722983
TI  - [The DNA-methylation state regulates virulence and stress response of
      Salmonella].
AB  - The DNA methylation is a post-replicative event that provides secondary
      information to that formed by DNA. Addition of this information involves DAM
      methyltransferase, which methylates DNA on specific sites (5'-GATC-3'). This
      modification of DNA may play a role in regulating various processes in eukaryote
      or prokaryote cells. It was well understood that deoxyadenosine methyltransferase
      (DAM) methylates the adenine of the GATC sequence. Following DNA replication,
      however, DNA is transiently hemimethylated, and the new strand is then methylated
      by DAM. In Escherichia coli, removing the dam gene produces several phenotypes
      indicating multiple functions of methylation: (i) modulation of gene expression,
      (ii) DNA repair, (iii) initiation of replication, and (iv) stabilising the
      chromosome.

PMID- 18722985
TI  - Territorial aggressiveness on the arboreal ant Azteca alfari by Camponotus
      blandus in French Guiana due to behavioural constraints.
AB  - This study reports new information on interactions between two sympatric ant
      species, the plant-ant Azteca alfari (Dolichoderinae) living in association with
      the myrmecophyte Cecropia obtusa (Cecropiaceae) and Camponotus blandus
      (Formicinae), a ground-nesting, arboreal-foraging species. Workers of A. alfari
      forage only on the foliage and the upper parts of the trunk of their host
      Cecropia, while C. blandus nests in the ground but frequently forages and patrols
      pioneer tree foliage, including Cecropia. The activity pattern of A. alfari and
      the number of C. blandus on Cecropia obtusa was monitored hourly during a two-day
      period in a disturbed area in French Guiana. The maximum activity of C. blandus
      occurred between 8:30 and 12:30, at which time A. alfari had retreated within the
      domatia and were least present on the trunks. Even though aggressive
      confrontations were observed, C. blandus workers often initiate confrontations
      but do not prey on A. alfari nor exploit food bodies produced by Cecropia, the
      principal food source of A. alfari. Hence hostility appears to be the result of
      territoriality. Differences in their foraging rhythms are proposed as promoting
      resource and territory partitioning in this ant assemblage.

PMID- 18722984
TI  - Biochemical evaluation of hepatic damage in subchronic exposure to malathion in
      rats: effect on superoxide dismutase and catalase activities using native PAGE.
AB  - The aim of this study was the evaluation of the hepatic damages following a
      subchronic exposure to malathion, an organophosphorus (OP) insecticide. Malathion
      was administered intragastrically in 1 ml corn oil containing 100 mg/kg Body
      Weight daily for 32 days. Malondialdehyde (MDA) concentration superoxide
      dismutase (SOD) and catalase (CAT) activities were analysed using a non
      denaturing electrophoresis. The serum activities of Pseudocholinesterase (PchE),
      aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were
      determined. Malathion exposure leads to a significant decrease in AchE activity,
      an increase in hepatic MDA, and in serum ASAT and ALAT activities. A positive
      correlation between serum transaminases levels and hepatic MDA was demonstrated.
      These results indicate that malathion exposure induced lipid peroxidation LPO, a
      process of degradation of membrane lipids, involving the deterioration of the
      cellular integrity. We have recorded a slight increase in antioxidant enzymes
      activities. This leads us to suggest an insufficient elimination of free
      radicals, causing cytotoxic effects.

PMID- 18722986
TI  - Low community photosynthetic quotient in coral reef sediments.
AB  - Fluxes of dissolved inorganic carbon and oxygen at the water-sediment interface
      were measured at eight coral reef stations (Indian Ocean) in summer and winter.
      The dark fluxes provided the community respiratory quotient (CRQ = dissolved
      inorganic carbon release / oxygen uptake) and the diurnal fluxes corrected from
      the dark fluxes gave the community photosynthetic quotient (CPQ = oxygen gross
      release / dissolved inorganic carbon gross uptake). The CRQ and the winter CPQ
      were not significantly different from 1. Summer CPQ (0.79; SD 0.02) was
      significantly lower than 1 due to the combined effect of the daily evolution of
      the community respiration and the discrepancy between the daily evolution in
      community oxygen respiration and community carbon respiration. These results
      highlight the importance of measuring simultaneously the benthic community
      production and respiration for long term integrated data sets, instead of the
      traditional daily or seasonal budget calculations from limited measures of
      community respiration.

PMID- 18722987
TI  - The impact of the 2003 summer heat wave and the 2005 late cold wave on the
      phytoplankton in the north-eastern English Channel.
AB  - The phytoplankton composition was investigated at two fixed stations in the north
      eastern English Channel from November 1997 to December 2005. The warmest
      temperatures in European historical records were recorded in August 2003. This
      event was associated with an exceptional abundance peak of the dinoflagellates
      Akashiwo sanguinea (9600 cells L(-1)) and Ceratium fusus. The lowest February
      temperatures for the 1998-2005 period were recorded in 2005, coinciding with the
      absence, for the first time in recent decades, of the spring bloom of Phaeocystis
      globosa. The 'de-eutrophication', mainly the reduction of river nutrient loads,
      is progressively reducing the magnitude of the Phaeocystis blooms. Exceptionally
      in 2005, the colder temperatures increased water column mixing, favouring the
      dominance of tychoplanktonic diatoms until early March (pre-bloom period). The
      delay in spring stratification, lower light availability due to turbidity
      (resuspended sediment) and organic matter, and competition with tychoplanktonic
      diatoms contributed to retard the timing of the spring phytoplankton bloom and
      disadvantage the development of Phaeocystis. The summer 2003 European heat wave
      is expected to have had little influence on total annual primary production,
      because it occurred at mid-summer, the period of lowest annual phytoplankton
      abundance. However, the anomalous weather in the second half of winter 2005 did
      affect the annual primary production.

PMID- 18722988
TI  - Measuring rodent incisors from scats can increase accuracy of predator diet
      studies. An illustration based on island cats and rats.
AB  - Non-invasive diet studies, which are a simple but important tool to understand
      trophic interactions inside ecosystems, need to be as detailed as possible.
      Determining the precise biomass of ingested prey is a key to obtaining not only a
      better understanding of the amount of food really ingested but also the predator
      prey interactions. It is particularly relevant in the case of rodents, because
      they are often a predominant prey in carnivores' diet and can differ widely in
      biomass. This study demonstrates how an original and simple method for measuring
      rat incisors found in cat scats produces measurements which can be correlated
      with rat weight. This correlation, used in a field application, made it possible
      to: (i) calculate a more accurate biomass of rats in cat diets and thus obtain a
      better estimation of the proportion of rats compared to other prey in cat diets;
      (ii) show that cats preferentially ate smaller rats, indicating that the use of
      the mean weight of rodents sampled by trap-lines may induce a significant bias in
      the biomass calculation. Likewise, a correlation between rat lens weight and
      incisor measurements was found. Using this correlation, it should be possible to
      estimate the age of the rats eaten by cats and obtain a better understanding of
      the impact of predators on prey population dynamics.

PMID- 18722989
TI  - [Distribution of zooplankton community in Mediterranean-climate lakes].
AB  - The sometimes sharp thermal variations and irregular precipitations and force
      concentrated over short periods characterize the Mediterranean climate. The
      structure of the zooplanktonic settlement was analyzed during one year in three
      Algerian reservoirs (lakes) with different geographical and climatic situation,
      in relation to abiotic factors (temperature, dissolved oxygen, pH, suspended
      matter, carbonates, nitrogenized and phosphorated nutritive salts). A canonical
      correspondence analysis was used to estimate the influence of the abiotic factors
      on the temporal distribution. The studied lakes are located, on the one hand, in
      northern Algeria, in a sub-humid area (Lake Boukourdane) and, on the other hand,
      in the South of the country, in the arid region (Foum El Ghorza and Djorf Torba).
      Analysis of the environmental parameters indicates that there is a seasonal
      variation in the three reservoirs. In Lake Foum El Ghorza, the temperature and
      hydrology variations, linked with the arid climate, affects the concentration of
      dissolved oxygen, which strongly decreases (1.5 mg/l), involving a pH reduction;
      suspended matters are sometimes high, coming from the stripped catchment area,
      causing a turbidity in this not very deep lake. The study of the distribution of
      the species allowed us to highlight a seasonal temporal variation. Lake
      Boukourdane, in the sub-humid zone, has an increased specific richness (SR=13).
      The various species evolve in alternation during the annual cycle. The
      representative species of this lake is Copidodiaptomus numidicus, characteristic
      of the rainy and endemic zone of the western Mediterranean; it is dominant (67%)
      in the spring. The Stenothermal species Diaphanosoma brachyurum, endemic of hot
      waters, is common to the two lakes; it evolves particularly in the summer (51.3%)
      at Boukourdane, whereas it is perennial and dominant (55%) in the spring at Djorf
      Torba. The specific richness is lower in Djorf Torba (SR=7) and in Foum El Ghorza
      (SR=6). The species collected in these two lakes are common and cosmopolitan, but
      they are adapted to the extreme conditions of the arid climate. Nevertheless, the
      species evolving in Lake Foum El Ghorza have undergone a significant decline,
      which has reduced the number of species and their density in the summer-autumn
      period. Thus, we can say that in the studied lakes, the hydrological factors and
      the temperature related to the Mediterranean climate would be two of the
      principal causes of the temporal distribution of the species.

PMID- 18722990
TI  - Tetraploid citrus rootstocks are more tolerant to salt stress than diploid.
AB  - Citrus trees are subject to several abiotic constraints such as salinity.
      Providing new rootstocks more tolerant is thus a requirement. In this article, we
      investigated salt stress tolerance of three tetraploid rootstock genotypes when
      compared to their respective diploid rootstocks (Poncirus trifoliata, Carrizo
      citrange, Cleopatra mandarin). Plant growth, leaf fall and ion contents were
      investigated. At the end of the experiment, leaf fall was observed only for
      diploid Poncirus trifoliata plants as well as chlorosis symptoms for Poncirus
      trifoliata and Carrizo citrange diploid plants. The diploid Cleopatra mandarin
      plants growth rate was not affected by salt stress and has even been increased
      for tetraploid Cleopatra mandarin. Ion contents investigation has shown lower
      accumulations of chloride ions in leaves of the tetraploid plants when compared
      to diploid plants. Our results suggest that citrus tetraploid rootstocks are more
      tolerant to salt stress than their corresponding diploid.

PMID- 18722991
TI  - Clinico-pathological effects of Schistosoma mansoni infection associated with
      simultaneous exposure to malathion in Swiss outbred albino mice.
AB  - To investigate whether infection of Swiss outbred mice with the digenetic fluke
      Schistosoma mansoni is influenced by exposure to environmental pollutants,
      experimentally infected mice were exposed to 200 and 400 mg/kg of malathion.
      Pathology of liver and spleen, worm burden and levels of key hematological,
      biochemical and liver enzymes parameters of these mice were evaluated and were
      compared with data from infected, unexposed mice, uninfected, exposed mice as
      well as with data from uninfected, unexposed mice. Oral administration of
      malathion to mice infected with 20, 40 or 60 S. mansoni cercariae adversely
      affect architecture of liver and spleen and critically alter hematological,
      biochemical, histological and hepatic enzymes parameters significantly more than
      the controls. Alterations observed in infected, exposed mice included (i) higher
      mortality rate; (ii) severe pathologies in liver and spleen; (iii) increased
      serum level of bilirubin and alanine aminotransferase/aspartate aminotransferase
      (ALT/AST) enzymes; (iv) decreased serum level of albumin and total proteins; and
      (v) decreased red blood cell count (RBC), lymphocytes, leucocytic count, and
      hemoglobin content. The number of recovered adult worms of S. mansoni or their
      oviposition capacity did not seem to be affected with malathion treatment.
      Statistical analysis revealed that the increase alteration in hepatic functions
      is correlated with increasing the number of S. mansoni cercariae and malathion
      doses. Such alterations were more significant in mice treated with the higher
      dose of malathion or infected with the largest numbers of S. mansoni cercariae.
      These data indicate that schistosomiasis can be exacerbated by simultaneous
      malathion exposure, which in turn adversely impact the clinical and pathological
      outcome of the disease.

PMID- 18722992
TI  - Image-based evaluation of the molecular events underlying HC11 mammary epithelial
      cell differentiation.
AB  - We have developed an image-based technique for signal pathway analysis, target
      validation, and compound screening related to mammary epithelial cell
      differentiation. This technique used the advantages of optical imaging and the
      HC11-Lux model system. The HC11-Lux cell line is a subclone of HC11 mammary
      epithelial cells transfected stably with a luciferase construct of the beta
      casein gene promoter (p-344/-1betac-Lux). The promoter activity was imaged
      optically in real time following lactogenic induction. The imaging signal
      intensity was closely correlated with that measured using a luminometer following
      protein extraction (R=0.99, P<0.0001) and consistent with the messenger RNA
      (mRNA) level of the endogenous beta -casein gene. Using this technique, we
      examined the roles of JAK2/Stat5A, Raf-1/MEK/MAKP, and PI3K/Akt signal pathways
      with respect to differentiation. The imaging studies showed that treatment of the
      cells with epidermal growth factor (EGF), AG490 (JAK2-specific inhibitor), and
      LY294002 (PI3K-specific inhibitor) blocked lactogenic differentiation in a dose
      dependent manner. PD98059 (MEK-specific inhibitor) could reverse EGF-mediated
      differentiation arrest. These results indicate that these pathways are essential
      in cell differentiation. This simple, sensitive, and reproducible technique
      permits visualization and real-time evaluation of the molecular events related to
      milk protein production. It can be adopted for high-throughput screening of small
      molecules for their effects on mammary epithelial cell growth, differentiation,
      and carcinogenesis.

PMID- 18722993
TI  - Critical factors for the performance of chip array-based electrical detection of
      DNA for analysis of pathogenic bacteria.
AB  - Different factors influencing chip array-based electrical detection of DNA for
      analysis of pathogenic bacteria were examined. Both rehydration of capture probe
      layer of functionalized chip arrays and efficient hybridization of targets
      irrespective of their length resulted in signal enhancement when high-ionic
      phosphate-buffered saline (i.e., 600mM sodium chloride and 40mM disodium hydrogen
      phosphate) was used. Similarly, placement of two adjacent capture and detection
      probe-binding sites at a terminal part of the target strand resulted in
      significant signal increase. Moreover, 10-min ultrasonic fragmentation of targets
      amplified the signals up to twofold for longer DNA strands (i.e., >300bp). No
      obvious effects on signals were visible for shorter than 400-bp PCR amplicons
      subjected to ultrasonication. For DNA strands of all sizes, more than 10min
      ultrasonication diminished the specific electrical responses. Our results also
      demonstrate that target analytes are detected with discrimination against
      mismatches even for single nucleotide sequence alteration. The mismatch detection
      appeared in order of ease of recognition as follows: triple random>quintuple
      middle>triple middle>single middle mismatch. Among the three variants of one-base
      mismatches, a sequence variation was most remarkable for adenine. On the other
      hand, no benefits in assay sensitivity were recognized by the use of longer
      capture probe linkers as the 6-C linker.

PMID- 18722994
TI  - Application of statistical design for the optimization of amino acid separation
      by reverse-phase HPLC.
AB  - Modified resolution and overall separation factors used to quantify the
      separation of complex chromatography systems are described. These factors were
      proven to be applicable to the optimization of amino acid resolution in reverse
      phase (RP) HPLC chromatograms. To optimize precolumn derivatization with
      phenylisothiocyanate, a 2(5-1) fractional factorial design in triplicate was
      employed. The five independent variables for optimizing the overall separation
      factor were triethylamine content of the aqueous buffer, pH of the aqueous
      buffer, separation temperature, methanol/acetonitrile concentration ratio in the
      organic eluant, and mobile phase flow rate. Of these, triethylamine concentration
      and methanol/acetonitrile concentration ratio were the most important. The
      methodology captured the interaction between variables. Temperature appeared in
      the interaction terms; consequently, it was included in the hierarchic model. The
      preliminary model based on the factorial experiments was not able to explain the
      response curvature in the design space; therefore, a central composite design was
      used to provide a quadratic model. Constrained nonlinear programming was used for
      optimization purposes. The quadratic model predicted the optimal levels of the
      variables. In this study, the best levels of the five independent variables that
      provide the maximum modified resolution for each pair of consecutive amino acids
      appearing in the chromatograph were determined. These results are of utmost
      importance for accurate analysis of a subset of amino acids.

PMID- 18722995
TI  - Elimination of keratin artifact bands from western blots by using low
      concentrations of reducing agents.
AB  - We encountered beta-mercaptoethanol-dependent artifact signals in western blot
      analyses using polyclonal antisera. Replacing beta-mercaptoethanol with
      dithiothreitol in the loading buffer did not eliminate the artifact signals.
      However, lowering the concentration of either dithiothreitol or beta
      mercaptoethanol eliminated the background problems and allowed specific detection
      of the target protein. These results are consistent with the background signal
      being caused by anti-keratin antibodies in the antisera and keratin contamination
      of reagents. This study highlights the importance of testing a range of reducing
      agent concentrations when trying to eliminate artifact bands from western blots.
      However, this method may not be applicable when target proteins have disulfide
      bridges.

PMID- 18722996
TI  - Signal amplification of target protein on heparin glycan microarray.
AB  - A heparin glycan chip (HepGlyChip) with a 4800-fold enhanced signal-to-noise
      ratio as compared with the control without heparin was developed for high
      throughput analysis of heparin-protein interactions for new drug development and
      for screening biological samples in diagnostic applications. As a proof of
      concept, a heparin glycan microarray was prepared on a poly(styrene-co-maleic
      anhydride) (PS-MA)-coated glass slide. Heparin was covalently immobilized on poly
      l-lysine (PLL) layer with multiple binding sites by sulfo-ethylene glycol
      bis(succinimidylsuccinate) (sulfo-EGS), increasing the signal-to-noise ratio,
      minimizing nonspecific binding of target proteins, and resulting in a three
      dimensional (3D) structure on the HepGlyChip. This on-chip signal amplification
      platform was successfully demonstrated by probing the heparin microarray with the
      highly specific heparin-binding protein antithrombin III (AT III).

PMID- 18722997
TI  - Propidium iodide-based methods for monitoring drug action in the kinetoplastidae:
      comparison with the Alamar Blue assay.
AB  - The urgent need for new drug development for African trypanosomiasis is widely
      recognized. This requires reliable and informative high-throughput assays.
      Currently, drug action is determined with a fluorimetric/colorimetric assay based
      on the metabolism of the dye Alamar Blue (resazurin) by live cells. However, this
      assay does not easily distinguish between cell death and growth arrest, or supply
      information about the rate at which test compounds affect these parameters. We
      report here an alternative fluorimetric assay, based on the interaction of
      propidium iodide with DNA, that allows either real-time monitoring of cell
      viability or the generation of EC(50) values at a predetermined time-point. The
      assay is highly sensitive and fluorescence readings easily correlate to numbers
      of parasites or DNA content. The EC(50) values were highly similar to those
      obtained with the standard Alamar Blue assay. The procedure lends itself readily
      to applications in drug development or resistance monitoring.

PMID- 18722998
TI  - AhR/Arnt:XRE interaction: turning false negatives into true positives in the
      modified yeast one-hybrid assay.
AB  - Given the frequent occurrence of false negatives in yeast genetic assays, it is
      both interesting and practical to address the possible mechanisms of false
      negatives and, more important, to turn false negatives into true positives. We
      recently developed a modified yeast one-hybrid system (MY1H) useful for
      investigation of simultaneous protein-protein and protein:DNA interactions in
      vivo. We coexpressed the basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) domains
      of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear
      translocator (Arnt)--namely NAhR and NArnt, respectively--which are known to form
      heterodimers and bind the cognate xenobiotic response element (XRE) sequence both
      in vitro and in vivo, as a positive control in the study of XRE-binding proteins
      in the MY1H system. However, we observed negative results, that is, no positive
      signal detected from binding of the NAhR/NArnt heterodimer and XRE site. We
      demonstrate that by increasing the copy number of XRE sites integrated into the
      yeast genome and using double GAL4 activation domains, the NAhR/NArnt heterodimer
      forms and specifically binds the cognate XRE sequence, an interaction that is now
      clearly detectable in the MY1H system. This methodology may be helpful in
      troubleshooting and correcting false negatives that arise from unproductive
      transcription in yeast genetic assays.

PMID- 18722999
TI  - The role of sphingomyelin in regulating phase coexistence in complex lipid model
      membranes: competition between ceramide and cholesterol.
AB  - The structure, thermotropic phase behavior, dynamic motion and order parameters
      of bilayer dispersions of egg phosphatidylcholine, egg sphingomyelin, egg
      ceramide and cholesterol have been determined. The coexistence of gel, liquid
      ordered and liquid-disordered structure has been determined by peak fitting
      analysis of synchrotron X-ray powder patterns. Order parameters and extent of
      distribution of 16-doxyl-stearic acid spin probe between ordered and disordered
      environments has been estimated by ESR spectral simulation methods. The presence
      of ceramide in proportions up to 20 mol% in phosphatidylcholine is characterized
      by gel-fluid phase coexistence at temperatures up to 46 degrees C depending on
      the amount of ceramide. Cholesterol tends to destabilize the ceramide-rich
      domains formed in phosphatidylcholine while sphingomyelin, by formation of stable
      complexes with ceramide, tends to stabilize these domains. The stability of
      sphingomyelin-ceramide complexes is evident from the persistence of highly
      ordered structure probed by ESR spectroscopy and appearance of a sharp wide-angle
      X-ray reflection at temperatures higher than the gel-fluid transition of ceramide
      alone in egg phosphatidylcholine bilayers. The competition between ceramide and
      cholesterol for interaction with sphingomyelin is discussed in terms of control
      of lipid-mediated signaling pathways by sphingomyelinase and phospholipase A2.

PMID- 18723000
TI  - Akt kinase reducing endoplasmic reticulum Ca2+ release protects cells from Ca2+
      dependent apoptotic stimuli.
AB  - The proto-oncogene Akt is a potent inhibitor of apoptosis, and it is activated in
      many human cancers. A number of recent studies have highlighted the importance of
      the inositol 1,4,5-trisphosphate (IP3) receptor(IP3R) in mediating calcium (Ca2+)
      transfer from the endoplasmic reticulum (ER) to the mitochondriain several models
      of apoptosis. Akt is a serine-threonine kinase and recent data indicate the IP3R
      as a target of its phosphorylation activity. Here we show that HeLa cells,
      overexpressing the constitutively active myristoylated/palmitylatedAKT1 (m/p
      AKT1), were found to have a reduced Ca2+ release from ER after stimulation with
      agonist coupled to the generation of IP3. In turn, this affected cytosolic and
      mitochondria Ca2+ response after Ca2+release from the ER induced either by
      agonist stimulation or by apoptotic stimuli releasing Ca2+ from intracellular
      stores. Most importantly, this alteration of ER Ca2+ content and release, reduces
      significantly cellular sensitivity to Ca2+ mediated proapoptotic stimulation.
      These results reveal a primary role of Akt in shaping intracellular Ca2+
      homeostasis, that may underlie its protective role against some proapoptotic
      stimuli.

PMID- 18723001
TI  - Inhibition of GIP signaling modulates adiponectin levels under high-fat diet in
      mice.
AB  - Gastric inhibitory polypeptide (GIP) is an incretin and directly promotes fat
      accumulation in adipocytes. Inhibition of GIP signaling prevents onset of obesity
      and increases fat oxidation in peripheral tissues under high-fat diet (HFD), but
      the mechanism is unknown. In the present study, we investigated the effects of
      inhibition of GIP signaling on adiponectin levels after 3 weeks of HFD by
      comparing wild-type (WT) mice and GIP receptor-deficient (Gipr(-/-)) mice. In HFD
      fed Gipr(-/-) mice, fat oxidation was significantly increased and adiponectin
      mRNA levels in white adipose tissue and plasma adiponectin levels were
      significantly increased compared to those in HFD-fed WT mice. In addition, the
      PPARalpha mRNA level was increased and the ACC mRNA level was decreased in
      skeletal muscle of HFD-fed Gipr(-/-) mice compared with those in HFD-fed WT mice.
      These results indicate that inhibition of GIP signaling increases adiponectin
      levels, resulting in increased fat oxidation in peripheral tissues under HFD.

PMID- 18723002
TI  - Involvement of gD/HVEM interaction in NF-kB-dependent inhibition of apoptosis by
      HSV-1 gD.
AB  - In the present paper, we aimed to verify whether the interaction of the
      glycoprotein D (gD) of herpes simplex 1 (HSV-1) with the HSV-1 receptor HVEM is
      involved in NF-kappaB-dependent protection against apoptosis by gD. To this
      purpose, first we utilized MAbs that interfere with gD/HVEM interaction and U937
      cells that naturally express human HVEM on their surface. Pre-incubation with
      these MAbs, but not with a control antibody, partially reverted the protection of
      infectious HSV-1 towards anti-Fas induced apoptosis in U937 cells. Similarly, pre
      incubation of UV-inactivated HSV-1 (UV-HSV-1) or recombinant gD with the same
      MAbs, significantly reduced the inhibition of Fas-mediated apoptosis by UV-HSV-1
      or gD, respectively, in U937 cells. Moreover, coculture with stable transfectants
      expressing at surface level wild type gD protected U937 cells against Fas-induced
      apoptosis, while coculture with transfectants expressing a mutated form of gD,
      incapable to bind HVEM, did not protect. Finally, UV-HSV-1 protected against
      staurosporine-induced apoptosis in U937 cells as well as in the CHO transfectants
      expressing human HVEM on their surface, but not in the control CHO transfectants,
      which did not express HVEM. These results suggest that signaling triggered by
      binding of gD to HVEM could represent an additional mechanism of evasion from
      premature apoptotic death exerted by HSV-1-gD in HVEM-expressing cells,
      disclosing new opportunities of cell death manipulation by using gD preparations.

PMID- 18723005
TI  - Changes in gamma-band power and phase synchronization with the difficulty of a
      visual oddball task.
AB  - We examined local and global differences in neuronal association patterns due to
      task difficulty. Induced and evoked gamma-band activity (GBA) was investigated
      using electroencephalograms recorded during visual oddball tasks of two
      difficulty levels. Significant phase synchronization (PS) in the gamma-band was
      determined by a double-threshold strategy, devised to detect prominent increases
      with respect to prestimulus baseline and surrogate data. A considerable increase
      in the early evoked GBA was observed for both difficulties, and this tended to be
      delayed for the hard task. Induced GBA was increased at the P300 latency period,
      but no difficulty-related change was observed. Intense PS among anterior and
      posterior regions along the midline was observed in a 30-38 Hz band, which was
      enhanced in the easy task throughout task execution, although the overall pattern
      of connectivity was similar for both difficulties. This may be the underlying
      basis of the faster and more accurate response to the easy task. The results
      showed that the most apparent change in the gamma-band associated with difficulty
      was observed in the PS pattern, not in the spectral power itself. This may imply
      that the difficulty-related change in cortical information processing was
      implemented as a change in the spatiotemporal pattern of interregional
      connectivity.

PMID- 18723003
TI  - Parallel perceptual enhancement and hierarchic relevance evaluation in an audio
      visual conjunction task.
AB  - Attention directs limited-capacity information processing resources to a subset
      of available perceptual representations. The mechanisms by which attention
      selects task-relevant representations for preferential processing are not fully
      known. Triesman and Gelade's [Triesman, A., Gelade, G., 1980. A feature
      integration theory of attention. Cognit. Psychol. 12, 97-136.] influential
      attention model posits that simple features are processed preattentively, in
      parallel, but that attention is required to serially conjoin multiple features
      into an object representation. Event-related potentials have provided evidence
      for this model showing parallel processing of perceptual features in the
      posterior Selection Negativity (SN) and serial, hierarchic processing of feature
      conjunctions in the Frontal Selection Positivity (FSP). Most prior studies have
      been done on conjunctions within one sensory modality while many real-world
      objects have multimodal features. It is not known if the same neural systems of
      posterior parallel processing of simple features and frontal serial processing of
      feature conjunctions seen within a sensory modality also operate on conjunctions
      between modalities. The current study used ERPs and simultaneously presented
      auditory and visual stimuli in three task conditions: Attend Auditory (auditory
      feature determines the target, visual features are irrelevant), Attend Visual
      (visual features relevant, auditory irrelevant), and Attend Conjunction (target
      defined by the co-occurrence of an auditory and a visual feature). In the Attend
      Conjunction condition when the auditory but not the visual feature was a target
      there was an SN over auditory cortex, when the visual but not auditory stimulus
      was a target there was an SN over visual cortex, and when both auditory and
      visual stimuli were targets (i.e. conjunction target) there were SNs over both
      auditory and visual cortex, indicating parallel processing of the simple features
      within each modality. In contrast, an FSP was present when either the visual only
      or both auditory and visual features were targets, but not when only the auditory
      stimulus was a target, indicating that the conjunction target determination was
      evaluated serially and hierarchically with visual information taking precedence.
      This indicates that the detection of a target defined by audio-visual conjunction
      is achieved via the same mechanism as within a single perceptual modality,
      through separate, parallel processing of the auditory and visual features and
      serial processing of the feature conjunction elements, rather than by evaluation
      of a fused multimodal percept.

PMID- 18723004
TI  - Iron deficiency alters expression of genes implicated in Alzheimer disease
      pathogenesis.
AB  - Neonatal brain iron deficiency occurs after insufficient maternal dietary iron
      intake, maternal hypertension, and maternal diabetes mellitus and results in
      short and long-term neurologic and behavioral deficits. Early iron deficiency
      affects the genomic profile of the developing hippocampus that persists despite
      iron repletion. The purpose of the present study was threefold: 1) quantitative
      PCR confirmation of our previous microarray results, demonstrating upregulation
      of a network of genes leading to beta-amyloid production and implicated in
      Alzheimer disease etiology in iron-deficient anemic rat pups at the time of
      hippocampal differentiation; 2) investigation of the potential contributions of
      iron deficiency anemia and iron treatment to this differential gene expression in
      the hippocampus; and 3) investigation of these genes over a developmental time
      course in a mouse model where iron deficiency is limited to hippocampus, is not
      accompanied by anemia and is not repletable. Quantitative PCR confirmed altered
      regulation in 6 of 7 Alzheimer-related genes (Apbb1, C1qa, Clu, App, Cst3, Fn1,
      Htatip) in iron-deficient rats relative to iron-sufficient controls at P15.
      Comparison of untreated to treated iron-deficient animals at this age suggested
      the strong role of iron deficiency, not treatment, in the upregulation of this
      gene network. The non-anemic hippocampal iron-deficient mouse demonstrated
      upregulation of all 7 genes in this pathway from P5 to P25. Our results suggest a
      role for neonatal iron deficiency in dysregulation of genes that may set the
      stage for long-term neurodegenerative disease and that this may occur through a
      histone modification mechanism.

PMID- 18723006
TI  - Protective effects of vitamin E and curcumin on L-thyroxine-induced rat
      testicular oxidative stress.
AB  - Present study examines effects of curcumin and vitamin E on oxidative stress
      parameters, antioxidant defence enzymes and oxidized (GSSG) and reduced
      glutathione (GSH) levels in testis of L-thyroxine (T4)-induced hyperthyroid rats.
      The oxidative stress in T4-treated rat testis was evident from elevation in
      oxidative stress parameters such as lipid peroxide and protein carbonyl contents,
      decrease in superoxide dismutase (SOD) and catalase (CAT) activities and increase
      in glutathione peroxidase (GPx) activity. This is accompanied with decrease in
      number and mortality of epididymal sperms. When the T4-treated rats were fed with
      vitamin E and/or curcumin, the lipid peroxide and protein carbonyl contents in
      crude homogenates of testes decreased to normal level. Treatment of curcumin
      and/or vitamin E to T4-treated rats resulted in elevation of SOD level in
      postmitochondrial fraction (PMF) and mitochondrial fraction (MF) and CAT in PMF,
      with decreased GPx activity in MF. However, curcumin or vitamin E was unable to
      change GPx activity alone but in together they elevated the GPx in PMF of T4
      treated rat testis. Both the antioxidants are incapable of producing significant
      changes in GSH:GSSG ratio of PMF of T4-treated rats. In MF, GSH:GSSG ratio
      elevated and decreased respectively by curcumin and vitamin E treatments to T4
      treated rats, however, in together these antioxidants caused an elevated GSH:GSSG
      ratio with a value less than when vitamin E given alone to T4-treated rats.
      Vitamin E not the curcumin elevates total sperm count and percentage of live
      sperm impaired by hyperthyroid state. In summary, both vitamin E and curcumin are
      efficient in protecting testis from oxidative stress generated by T4 mainly in
      restoring antioxidant enzymes to the level of euthyroid animals up to some extent
      but vitamin E is more efficient than curcumin.

PMID- 18723007
TI  - The protozoan toxin climacostol inhibits growth and induces apoptosis of human
      tumor cell lines.
AB  - Climacostol (5-(Z)-non-2-enyl-benzene-1,3-diol) is a natural toxin isolated from
      the freshwater ciliated protozoan Climacostomum virens and belongs to the group
      of resorcinolic lipids, compounds that show antimicrobial, antiparasitic and
      antitumor activities. We investigated the cytotoxic activity of the chemically
      synthesized toxin on: (1) human tumor squamous carcinoma A431 cells, (2) human
      promyelocytic leukaemia HL60 cells, and (3) human non-tumor endothelial EA.hy926
      cells. The results showed that climacostol effectively inhibited the growth of
      tumor cell lines in a dose-dependent manner by inducing programmed cell death,
      with non-tumor cells proving significantly more resistant to the toxin.

PMID- 18723008
TI  - Efficacy of Siddha formulation Kalpaamruthaa in ameliorating joint destruction in
      rheumatoid arthritis in rats.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a kind of chronic inflammatory
      autoimmune disease. The degradation of extracellular matrix and cartilage pave
      way in understanding the molecular mechanisms in RA. Degradation of cartilage is
      a more complex event involving the local release of metallaoproteases and
      lysosomal enzymes that mediate inflammation in joints and in the synovial fluid
      in RA. OBJECTIVES: In the present study, the efficacy of a Siddha preparation
      named Kalpaamruthaa (KA) in ameliorating the disease process via markedly
      reducing the joint destruction was demonstrated in adjuvant induced arthritis rat
      model. KA consists of Semecarpus anacardium nut milk extract (SA), dried powder
      of Emblica officinalis fruit and honey. MATERIAL AND METHODS: Both SA and KA were
      administered at dose of 150 mg/kg b.wt. for 14 days after 14 days of adjuvant
      injection in rats. The activity of lysosomal enzymes, the level of collagen,
      glycosaminoglycans (GAGs) and its degradative products were analyzed in control
      and experimental animals. RESULTS AND CONCLUSION: The study revealed that KA
      exhibited a profound reduction (p<0.05) in the activities of lysosomal enzymes
      and thereby decreasing (p<0.05) the levels of GAGs and its fractions when
      compared to arthritis rats. The latter was confirmed by Safrannin O staining for
      GAGs in the interphalangeal joints of control and experimental animals. The
      effect of KA was found to be improved than SA and this might be due to the
      combined interactions of phytoconstituents present in KA.

PMID- 18723009
TI  - Membrane lipid domains and rafts: current applications of fluorescence lifetime
      spectroscopy and imaging.
AB  - Membrane microdomains and their involvement in cellular processes are part of the
      current paradigm of biomembranes. However, a better characterization of domains,
      namely lipid rafts, is needed. In this review, it is shown how the use of time
      resolved fluorescence, with the adequate parameters and probes, helps elucidating
      the type, number, fraction, composition and size of lipid phases and domains in
      multicomponent model systems. The determination of phase diagrams for lipid
      mixtures containing sphingolipids and/or cholesterol is exemplified. The use of
      fluorescence quenching and Forster resonance energy transfer (FRET) are also
      illustrated. Strategies for studying protein-induced domains are presented. The
      advantages of using single point microscopic decays and fluorescence lifetime
      imaging microscopy (FLIM) in systems with three-phase coexistence are explained.
      Finally, the introduction of FLIM allows studies in live cell membranes, and the
      nature of the microdomains observed is readily elucidated due to the information
      retrieved from fluorescence lifetimes.

PMID- 18723010
TI  - Technique for cryopreservation of intestinal smooth muscle cells.
AB  - Attempts were made to develop a simplified procedure for long-term
      cryopreservation of intestinal smooth muscle cells (ISMC). ISMC were collected
      from the ileum of Sprague-Dawley neonatal rats through cellular dissociation in
      trypsin. Cryopreservation method comprised of a rapid 1-step (protocol 1) and a
      slow 3-step (protocol 2) freezing of ISMC for 1week. Preparations were thawed and
      single ISMC were assessed via the comet assay and damaged DNA was quantified
      through comet tail moment. The control unfrozen ISMC exhibited DNA damage of
      2.34+/-0.35 compared to ISMC cooled via protocol 2 (2.62+/-0.36) and protocol 1
      (10.15+/-0.72). Thereafter, protocol 2 freezing method was adopted and ISMC were
      cryopreserved for 1-week, 1-month, and 4-months to analyse the temporal and long
      term cryopreservation of ISMC. This revealed a DNA damage of 2.62+/-0.36 (1
      week), 3.81+/-0.72 (1-month), and 5.1+/-0.9 (4-months). Gradual cooling is
      suitable for continuing storage of ISMC and although fluctuation in cryoinjury is
      observed with time this is considered to reflect cell-to-cell variability.

PMID- 18723012
TI  - Transcriptional cascade from Math1 to Mbh1 and Mbh2 is required for cerebellar
      granule cell differentiation.
AB  - Cerebellar granule cells (CGCs) are the most abundant neuronal type in the
      mammalian brain, and their differentiation is regulated by the basic helix-loop
      helix gene, Math1. However, little is known about downstream genes of Math1 and
      their functions in the cerebellum. To investigate them, we have here established
      an electroporation-based in vivo gene transfer method in the developing mouse
      cerebellum. Misexpression of Math1 ectopically induced expression of Bar-class
      homeobox genes, Mbh1 and Mbh2, which are expressed by CGCs. Conversely, their
      expression was repressed in CGCs by knockdown of Math1. These findings, taken
      together with chromatin immunoprecipitation assays, suggest that Math1 directly
      regulates the Mbh genes in CGCs. Furthermore, a dominant-negative form of the Mbh
      proteins disrupted proper formation of the external granule layer and
      differentiation of CGCs, whereas misexpression of the Mbh genes ectopically
      induced expression of a CGC marker in nonneuronal cells, indicating that the Mbh
      proteins are required for the differentiation of CGCs.

PMID- 18723011
TI  - A dosage-dependent requirement for Sox9 in pancreatic endocrine cell formation.
AB  - We have previously shown the transcription factor SOX9 to be required for the
      maintenance of multipotential pancreatic progenitor cells in the early embryonic
      pancreas. However, the association of pancreatic endocrine defects with the Sox9
      haploinsufficiency syndrome campomelic dysplasia (CD) implies additional later
      roles for Sox9 in endocrine development. Using short-term lineage tracing in
      mice, we demonstrate here that SOX9 marks a pool of multipotential pancreatic
      progenitors throughout the window of major cell differentiation. During mid
      pancreogenesis, both endocrine and exocrine cells simultaneously arise from the
      SOX9(+) epithelial cords. Our analysis of mice with 50%-reduced Sox9 gene dosage
      in pancreatic progenitors reveals endocrine-specific defects phenocopying CD. By
      birth, these mice display a specific reduction in endocrine cell mass, while
      their exocrine compartment and total organ size is normal. The decrease in
      endocrine cells is caused by reduced generation of endocrine progenitors from the
      SOX9(+) epithelium. Conversely, formation of exocrine progenitors is insensitive
      to reduced Sox9 gene dosage, thus explaining the normal organ size at birth. Our
      results show that not only is SOX9 required for the maintenance of early
      pancreatic progenitors, but also governs their adoption of an endocrine fate. Our
      findings therefore suggest that defective endocrine specification might underlie
      the pancreatic phenotype of individuals with CD.

PMID- 18723013
TI  - Expression of BMP7 is associated with resistance to diabetic stress: comparison
      among mouse salivary glands.
AB  - We determined mRNA levels of bone morphogenetic protein 7 (BMP7), a growth and
      differentiation factor belonging to the transforming growth factor-beta
      superfamily, in the salivary glands of mice with streptozotocin (200 mg/kg, i.p.)
      induced diabetes. We also examined the effects of BMP7 on secretion of saliva and
      degenerative change in salivary glands in diabetic mice. In normal mice, BMP7
      mRNA levels were high in the submandibular gland and low in the parotid gland,
      while in diabetic mice, levels were significantly decreased in the parotid gland,
      but not in the submandibular gland. No significant difference was observed in
      mRNA levels of BMP receptors between normal and diabetic mice. In diabetic mice,
      pilocarpine (4 mg/kg, i.p.)-stimulated salivary secretion showed a remarkable
      decrease in both parotid and submandibular gland, although degree of reduction
      was smaller in the latter. Notable degeneration with vacuolation and atrophy was
      also found in parotid gland, whereas degeneration of submandibular gland was
      slight. Administration of BMP7 (50 and 100 microg/kg, i.v.) in diabetic mice
      induced a significant increase in salivary secretion, with rate of recovery
      higher in parotid gland than in submandibular gland. In diabetic mice, BMP7 also
      exhibited a powerful protective effect in degenerated salivary gland, especially
      in parotid gland. These results suggest that BMP7 acts to prevent diabetic damage
      in salivary gland, and that its cytoprotective effect is closely correlated with
      mRNA levels in tissue.

PMID- 18723014
TI  - Cataracts in transgenic mice caused by a human papillomavirus type 18 E7 oncogene
      driven by KRT1-14.
AB  - Human papillomavirus type 18 (HPV18) is a common cause of cervical cancer. To
      create a mouse model for this common neoplastic disease, we used a human keratin
      14 promoter to drive the HPV18 E7 oncogene to create transgenic mice. No mice up
      to a year of age developed cervical cancer. However, all transgenic mice and none
      of the controls developed progressive bilateral cortical cataracts. By 6 months
      of age, the cortex liquefied leaving the lens nucleus. Proliferation of lens
      epithelium formed multifocal nodules and free floating lens epithelial cells
      within the liquefied cortex. These cells were hyperplastic not neoplastic. Other
      HPV transgenic stocks develop cataracts suggesting this virus may have a broad
      cellular tropism.

PMID- 18723015
TI  - Anti-sphingosine-1-phosphate monoclonal antibodies inhibit angiogenesis and sub
      retinal fibrosis in a murine model of laser-induced choroidal neovascularization.
AB  - The efficacy of novel monoclonal antibodies that neutralize the pro-angiogenic
      mediator, sphingosine-1-phosphate (S1P), were tested using in vitro and in vivo
      angiogenesis models, including choroidal neovascularization (CNV) induced by
      laser disruption of Bruch's membrane. S1P receptor levels in human brain choroid
      plexus endothelial cells (CPEC), human lung microvascular endothelial cells,
      human retinal vascular endothelial cells, and circulating endothelial progenitor
      cells were examined by semi-quantitative PCR. The ability of murine or humanized
      anti-S1P monoclonal antibodies (mAbs) to inhibit S1P-mediated microvessel tube
      formation by CPEC on Matrigel was evaluated and capillary density in subcutaneous
      growth factor-loaded Matrigel plugs was determined following anti-S1P treatment.
      S1P promoted in vitro capillary tube formation in CPEC consistent with the
      presence of cognate S1P(1-5) receptor expression by these cells and the S1P
      antibody induced a dose-dependent reduction in microvessel tube formation. In a
      murine model of laser-induced rupture of Bruch's membrane, S1P was detected in
      posterior cups of mice receiving laser injury, but not in uninjured controls.
      Intravitreous injection of anti-S1P mAbs dramatically inhibited CNV formation and
      sub-retinal collagen deposition in all treatment groups (p<0.05 compared to
      controls), thereby identifying S1P as a previously unrecognized mediator of
      angiogenesis and subretinal fibrosis in this model. These findings suggest that
      neutralizing S1P with anti-S1P mAbs may be a novel method of treating patients
      with exudative age-related macular degeneration by reducing angiogenesis and sub
      retinal fibrosis, which are responsible for visual acuity loss in this disease.

PMID- 18723016
TI  - Evidence of dopamine dysfunction in the hypothalamus of patients with Parkinson's
      disease: an in vivo 11C-raclopride PET study.
AB  - A mild to moderate reduction in dopamine, noradrenaline and serotonin levels
      alongside a progressive loss of hypocretin cells and melanin hormone
      concentrating cells has been reported in the hypothalamus of PD at postmortem.
      Hypothalamic uptake of (18)F-dopa PET, an in vivo marker of dysfunction of
      monoaminergic neurons, is also significantly reduced in these patients. These
      data indicate a general impairment of hypothalamic function in PD. Dopamine
      receptors play an important role in the regulation of hypothalamic pathways. To
      date, possible changes in hypothalamic D(2) receptor availability have not been
      investigated in PD. The objective in this study was to assess dopamine D(2)
      receptor availability in hypothalamus of patients with idiopathic Parkinson's
      disease (PD) using positron emission tomography (PET) with (11)C-raclopride
      (RAC). We evaluated D(2) binding in RAC PET images of 14 PD patients using both
      region of interest (ROI) analysis and a voxel based approach. ROIs for the
      hypothalamus were traced on the subject's MRI co-registered to the PET image.
      (11)C-raclopride binding potentials (BP) for hypothalamus were obtained by
      applying ROIs onto parametric images. Findings were compared with those of 9
      normal controls. We found a significant reduction in the mean hypothalamic RAC BP
      of the PD patients compared with the normal controls (0.2714+/-0.06 vs. 0.3861+/
      0.04; mean+/-SD; p=0.0005). ROI results were confirmed with statistical
      parametric mapping (SPM). Individual hypothalamic BP values of PD patients did
      not correlate with age, disease duration, disease severity and levodopa
      equivalent dose. It remains to be ascertained whether the reductions in
      hypothalamic D(2) receptor availability seen in PD are disease related, the
      results of chronic exposure to levodopa or both. Our results provide further
      evidence of dopaminergic dysfunction in the hypothalamus in PD, and this may
      contribute to the development of sleep, endocrine and autonomic disorders.

PMID- 18723017
TI  - DUX4c, an FSHD candidate gene, interferes with myogenic regulators and abolishes
      myoblast differentiation.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant
      neuromuscular disease. It maps to the D4Z4 repeat array at 4q35, and correlates
      with a repeat contraction which derepresses transcription of local genes. Which,
      if any, of these genes is pathogenic to muscle, and through what molecular
      mechanism is unknown. The present study investigates the function of one
      candidate gene, DUX4c, encoded by a truncated inverted D4Z4 element located 42 kb
      proximal to the D4Z4 repeats. Using a gain of function approach we tested DUX4c
      for toxicity and effects on differentiation in C2C12 myoblasts. DUX4c-expressing
      myoblasts appear morphologically normal but have reduced expression of myogenic
      regulators, including MyoD and Myf5. Consistent with this, DUX4c-expressing
      myoblasts are unable to differentiate into myotubes. Furthermore, overexpression
      of Myf5 or MyoD rescued myoblast differentiation, suggesting that reductions in
      expression of these regulators are the relevant DUX4c-induced physiological
      changes that inhibit differentiation. Our results suggest that upregulation of
      DUX4c can have a deleterious effect on muscle homeostasis and regeneration, and
      point to a possible role for DUX4c in the pathology of FSHD.

PMID- 18723018
TI  - Inhibitory control test for the diagnosis of minimal hepatic encephalopathy.
AB  - BACKGROUND & AIMS: Minimal hepatic encephalopathy (MHE) is difficult to diagnose.
      The Inhibitory Control Test (ICT) measures response inhibition and has diagnosed
      MHE with 90% sensitivity and specificity in a selected population; high lure and
      low target rates indicated poor ICT performance. We studied the reliability and
      validity of ICT for MHE diagnosis. METHODS: ICT was compared with a psychometric
      battery (standard psychometric tests [SPT]) for MHE diagnosis and overt hepatic
      encephalopathy (OHE) prediction. ICT was administered twice for test-retest
      reliability, before/after transvenous intrahepatic portosystemic shunting (TIPS),
      and before/after yogurt treatment. The time taken by 2 medical assistants (MA) to
      administer ICT was recorded and compared with that of a psychologist for cost
      analysis. RESULTS: One hundred thirty-six cirrhotic patients and 116
      age/education-matched controls were studied. ICT (>5 lures) had 88% sensitivity
      for MHE diagnosis with 0.902 area under the curve for receiver operating
      characteristic. MHE-positive patients had significantly higher ICT lures (11 vs
      4, respectively, P = .0001) and lower targets (92% vs 97%, respectively, P =
      .0001) compared with MHE-negative patients. The test/retest reliability for ICT
      lures (n = 50, r = 0.90, P = .0001) was high. ICT and SPT were equivalent in
      predicting OHE (21%). ICT lures significantly worsened after TIPS (n = 10; 5 vs
      9, respectively; P = .02) and improved after yogurt supplementation (n = 18, 10
      vs 5, respectively; P = .002). The MAs were successfully trained to administer
      ICT; the time required for test administration and the associated costs were
      smaller for ICT than for SPT. CONCLUSIONS: ICT is a sensitive, reliable, and
      valid test for MHE diagnosis that can be administered inexpensively by MAs.

PMID- 18723019
TI  - Genome-wide association analysis in sarcoidosis and Crohn's disease unravels a
      common susceptibility locus on 10p12.2.
AB  - BACKGROUND & AIMS: Crohn's disease (CD) and sarcoidosis (SA) are chronic
      inflammatory barrier diseases that share several clinical and immunological
      features, including the occurrence of granulomas. METHODS: A 100k genome-wide
      association study with 83,360 single-nucleotide polymorphisms (SNPs) was
      performed on 382 CD patients, 398 SA patients, and 394 control individuals. The
      24 SNPs that were most strongly associated in the combined CD/SA phenotype were
      selected for verification in an independent sample of 1,317 patients (660 CD and
      657 SA) and 1,091 controls. RESULTS: The most significant association (Bonferroni
      corrected P = .036) was obtained at SNP rs1398024 on chromosome 10p12.2, with an
      odds ratio (OR) for both diseases of 0.81 (95% confidence interval [CI], 0.69
      0.96) for carriership of the rarer allele A. The P value in the overall combined
      sample was 4.24 x 10(-6). During further follow-up, a moderate association (OR,
      0.83; 95% CI, 0.72-0.96; P = .015) was observed between rs1398024 and ulcerative
      colitis (1,080 patients vs 1,091 controls), the second main subphenotype of
      inflammatory bowel disease in addition to CD. Extensive fine mapping of the
      10p12.2 locus points to yet unidentified variants in the C10ORF67 gene region as
      the most likely underlying risk factors. CONCLUSION: Our study demonstrates that
      the combined analysis of different, albeit clinically related, phenotypes can
      lead to the identification of common susceptibility loci.

PMID- 18723020
TI  - Serotonin interferes with Ca2+ and PKC signaling to reduce gonadotropin-releasing
      hormone-stimulated GH secretion in goldfish pituitary cells.
AB  - In goldfish, two endogenous gonadotropin-releasing hormones (GnRH), salmon GnRH
      (sGnRH) and chicken GnRH-II (cGnRH-II), are thought to stimulate growth hormone
      (GH) release via protein kinase C (PKC) and subsequent increases in intracellular
      Ca(2+) levels ([Ca(2+)](i)). In contrast, the signaling mechanism for serotonin
      (5-HT) inhibition of GH secretion is still unknown. In this study, whether 5-HT
      inhibits GH release by actions at sites along the PKC and Ca(2+) signal
      transduction pathways leading to hormone release were examined in primary
      cultures of goldfish pituitary cells. Under static incubation and column
      perifusion conditions, 5-HT reduced basal, as well as sGnRH- and cGnRH-II
      stimulated, GH secretion. 5-HT also suppressed GH responses to two PKC activators
      but had no effect on the GH-releasing action of the Ca(2+) ionophore ionomycin.
      Ca(2+)-imaging studies with identified somatotropes revealed that 5-HT did not
      alter basal [Ca(2+)](i) but attenuated the magnitude of the [Ca(2+)](i) responses
      to the two GnRHs. Prior treatment with 5-HT and cGnRH-II reduced the magnitude of
      the [Ca(2+)](i) responses induced by depolarizing levels of K(+). Similar
      inhibition, however, was not observed with prior treatment of 5-HT and sGnRH.
      These results suggest that 5-HT, by direct actions at the somatotrope level,
      interferes with PKC and Ca(2+) signaling pathways to reduce the GH-releasing
      effect of GnRH. 5-HT action may occur at the level of PKC activation or its
      downstream signaling events prior to the subsequent rise in [Ca(2+)](i.). The
      differential Ca(2+) responses by depolarizing doses of K(+) is consistent with
      our previous findings that sGnRH and cGnRH-II are coupled to overlapping and yet
      distinct Ca(2+)-dependent mechanisms.

PMID- 18723021
TI  - A kinetoplastid BRCA2 interacts with DNA replication protein CDC45.
AB  - The gene BRCA2, first identified as a breast cancer susceptibility locus in
      humans, encodes a protein involved in DNA repair in mammalian cells and mutations
      in this gene confer increased risk of breast cancer. Here we report a functional
      characterisation of a Trypanosoma brucei BRCA2 (TbBRCA2) orthologue and show that
      the protein interacts directly with TbRAD51. A further protein-protein
      interaction screen using TbBRCA2 identified other interacting proteins, including
      a trypanosome orthologue of CDC45 which is involved in initiation and progression
      of the replication fork complex during DNA synthesis. Deletion of the TbBRCA2
      gene retards cell cycle progression during S-phase as judged by increased
      incorporation of BrdU and an increased percentage of cells with one nucleus and
      two kinetoplasts. These results provide insights into the potential role played
      by BRCA2 in DNA replication and reveal a novel interaction that couples
      replication and recombination in maintaining integrity of the genome.

PMID- 18723024
TI  - The asymmetric trimeric architecture of [2Fe-2S] IscU: implications for its
      scaffolding during iron-sulfur cluster biosynthesis.
AB  - IscU is a key component of the ISC machinery and is involved in the biogenesis of
      iron-sulfur (Fe-S) proteins. IscU serves as a scaffold for assembly of a nascent
      Fe-S cluster prior to its delivery to an apo protein. Here, we report the first
      crystal structure of IscU with a bound [2Fe-2S] cluster from the
      hyperthermophilic bacterium Aquifex aeolicus, determined at a resolution of 2.3
      A, using multiwavelength anomalous diffraction of the cluster. The holo IscU
      formed a novel asymmetric trimer that harbored only one [2Fe-2S] cluster. One
      iron atom of the cluster was coordinated by the S(gamma) atom of Cys36 and the
      N(epsilon) atom of His106, and the other was coordinated by the S(gamma) atoms of
      Cys63 and Cys107 on the surface of just one of the protomers. However, the
      cluster was buried inside the trimer between the neighboring protomers. The three
      protomers were conformationally distinct from one another and associated around a
      noncrystallographic pseudo-3-fold axis. The three flexible loop regions carrying
      the ligand-binding residues (Cys36, Cys63, His106 and Cys107) and the N-terminal
      alpha1 helices were positioned at the interfaces and underwent substantial
      conformational rearrangement, which stabilized the association of the asymmetric
      trimer. This unique trimeric A. aeolicus holo-IscU architecture was clearly
      distinct from other known monomeric apo-IscU/SufU structures, indicating that
      asymmetric trimer organization, as well as its association/dissociation, would be
      involved in the scaffolding function of IscU.

PMID- 18723023
TI  - Imaging effector functions of human cytotoxic CD4+ T cells specific for
      Plasmodium falciparum circumsporozoite protein.
AB  - Malaria vaccines, comprised of irradiated Plasmodium falciparum sporozoites or a
      synthetic peptide containing T and B cell epitopes of the circumsporozoite
      protein (CSP), elicit multifunctional cytotoxic and non-cytotoxic CD4(+) T cells
      in immunised volunteers. Both lytic and non-lytic CD4(+)T cell clones recognised
      a series of overlapping epitopes within a 'universal' T cell epitope
      EYLNKIQNSLSTEWSPCSVT of CSP (NF54 isolate) that was presented in the context of
      multiple DR molecules. Lytic activity directly correlated with T cell receptor
      (TCR) functional avidity as measured by stimulation indices and recognition of
      naturally occurring variant peptides. CD4(+) T cell-mediated cytotoxicity was
      contact-dependent and did not require de novo synthesis of cytotoxic mediators,
      suggesting a granule-mediated mechanism. Live cell imaging of the interaction of
      effector and target cells demonstrated that CD4(+) cytotoxic T cells recognise
      target cells with their leading edge, reorient their cytotoxic granules towards
      the zone of contact, and form a stable immunological synapse. CTL attacks induced
      chromatin condensation, nuclear fragmentation and formation of apoptotic bodies
      in target cells. Together, these findings suggest that CD4(+) CTLs trigger target
      cell apoptosis via classical perforin/granzyme-mediated cytotoxicity, similar to
      CD8(+) CTLs, and these multifunctional sporozoite- and peptide-induced CD4(+) T
      cells have the potential to play a direct role as effector cells in targeting the
      exoerythrocytic forms within the liver.

PMID- 18723022
TI  - Schistosoma mansoni arginase shares functional similarities with human orthologs
      but depends upon disulphide bridges for enzymatic activity.
AB  - Schistosome helminths constitute a major health risk for the human population in
      many tropical areas. We demonstrate for the first time that several developmental
      stages of the human parasite Schistosoma mansoni express arginase, which is
      responsible for the hydrolysis of l-arginine to l-ornithine and urea. Arginase
      activity by alternatively activated macrophages is an essential component of the
      mammalian host response in schistosomiasis. However, it has not been previously
      shown that the parasite also expresses arginase when it is in contact with the
      mammalian host. After cloning and sequencing the cDNA encoding the parasite
      enzyme, we found that many structural features of human arginase are well
      conserved in the parasite ortholog. Subsequently, we discovered that S. mansoni
      arginase shares many similar molecular, biochemical and functional properties
      with both human arginase isoforms. Nevertheless, our data also reveal striking
      differences between human and schistosome arginase. Particularly, we found
      evidence that schistosome arginase activity depends upon disulphide bonds by
      cysteines, in contrast to human arginase. In conclusion, we report that S.
      mansoni arginase is well adapted to the physiological conditions that exist in
      the human host.

PMID- 18723025
TI  - Conserved central domains control the quaternary structure of type I and type II
      Hsp40 molecular chaperones.
AB  - Heat shock protein (Hsp)40s play an essential role in protein metabolism by
      regulating the polypeptide binding and release cycle of Hsp70. The Hsp40 family
      is large, and specialized family members direct Hsp70 to perform highly specific
      tasks. Type I and Type II Hsp40s, such as yeast Ydj1 and Sis1, are homodimers
      that dictate functions of cytosolic Hsp70, but how they do so is unclear. Type I
      Hsp40s contain a conserved, centrally located cysteine-rich domain that is
      replaced by a glycine- and methionine-rich region in Type II Hsp40s, but the
      mechanism by which these unique domains influence Hsp40 structure and function is
      unknown. This is the case because high-resolution structures of full-length forms
      of these Hsp40s have not been solved. To fill this void, we built low-resolution
      models of the quaternary structure of Ydj1 and Sis1 with information obtained
      from biophysical measurements of protein shape, small-angle X-ray scattering, and
      ab initio protein modeling. Low-resolution models were also calculated for the
      chimeric Hsp40s YSY and SYS, in which the central domains of Ydj1 and Sis1 were
      exchanged. Similar to their human homologs, Ydj1 and Sis1 each has a unique shape
      with major structural differences apparently being the orientation of the J
      domains relative to the long axis of the dimers. Central domain swapping in YSY
      and SYS correlates with the switched ability of YSY and SYS to perform unique
      functions of Sis1 and Ydj1, respectively. Models for the mechanism by which the
      conserved cysteine-rich domain and glycine- and methionine-rich region confer
      structural and functional specificity to Type I and Type II Hsp40s are discussed.

PMID- 18723026
TI  - The first structure of a glycoside hydrolase family 61 member, Cel61B from
      Hypocrea jecorina, at 1.6 A resolution.
AB  - The glycoside hydrolase (GH) family 61 is a long-recognized, but still recondite,
      class of proteins, with little known about the activity, mechanism or function of
      its more than 70 members. The best-studied GH family 61 member, Cel61A of the
      filamentous fungus Hypocrea jecorina, is known to be an endoglucanase, but it is
      not clear if this represents the main activity or function of this family in
      vivo. We present here the first structure for this family, that of Cel61B from H.
      jecorina. The best-quality crystals were formed in the presence of nickel, and
      the crystal structure was solved to 1.6 A resolution using a single-wavelength
      anomalous dispersion method with nickel as the source of anomalous scatter.
      Cel61B lacks a carbohydrate-binding module and is a single-domain protein that
      folds into a twisted beta-sandwich. A structure-aided sequence alignment of all
      GH family 61 proteins identified a highly conserved group of residues on the
      surface of Cel61B. Within this patch of mostly polar amino acids was a site
      occupied by the intramolecular nickel hexacoordinately bound in the solved
      structure. In the Cel61B structure, there is no easily identifiable carbohydrate
      binding cleft or pocket or catalytic center of the types normally seen in GHs. A
      structural comparison search showed that the known structure most similar to
      Cel61B is that of CBP21 from the Gram-negative soil bacterium Serratia
      marcescens, a member of the carbohydrate-binding module family 33 proteins. A
      polar surface patch highly conserved in that structural family has been
      identified in CBP21 and shown to be involved in chitin binding and in the
      protein's enhancement of chitinase activities. The analysis of the Cel61B
      structure is discussed in light of our continuing research to better understand
      the activities and function of GH family 61.

PMID- 18723028
TI  - Determining the most important cellular characteristics for fracture healing
      using design of experiments methods.
AB  - Computational models are employed as tools to investigate possible
      mechanoregulation pathways for tissue differentiation and bone healing. However,
      current models do not account for the uncertainty in input parameters, and often
      include assumptions about parameter values that are not yet established. The
      objective of this study was to determine the most important cellular
      characteristics of a mechanoregulatory model describing both cell phenotype
      specific and mechanobiological processes that are active during bone healing
      using a statistical approach. The computational model included an adaptive two
      dimensional finite element model of a fractured long bone. Three different
      outcome criteria were quantified: (1) ability to predict sequential healing
      events, (2) amount of bone formation at early, mid and late stages of healing and
      (3) the total time until complete healing. For the statistical analysis, first a
      resolution IV fractional factorial design (L(64)) was used to identify the most
      significant factors. Thereafter, a three-level Taguchi orthogonal array (L(27))
      was employed to study the curvature (non-linearity) of the 10 identified most
      important parameters. The results show that the ability of the model to predict
      the sequences of normal fracture healing was predominantly influenced by the rate
      of matrix production of bone, followed by cartilage degradation (replacement).
      The amount of bone formation at early stages was solely dependent on matrix
      production of bone and the proliferation rate of osteoblasts. However, the amount
      of bone formation at mid and late phases had the rate of matrix production of
      cartilage as the most influential parameter. The time to complete healing was
      primarily dependent on the rate of cartilage degradation during endochondral
      ossification, followed by the rate of cartilage formation. The analyses of the
      curvature revealed a linear response for parameters related to bone, where higher
      rates of formation were more beneficial to healing. In contrast, parameters
      related to fibrous tissue and cartilage showed optimum levels. Some fibrous
      connective tissue- and cartilage formation was beneficial to bone healing, but
      too much of either tissue delayed bone formation. The identified significant
      parameters and processes are further confirmed by in vivo animal experiments in
      the literature. This study illustrates the potential of design of experiments
      methods for evaluating computational mechanobiological model parameters and
      suggests that further experiments should preferably focus at establishing values
      of parameters related to cartilage formation and degradation.

PMID- 18723027
TI  - Organization and evolution of the biological response to singlet oxygen stress.
AB  - The appearance of atmospheric oxygen from photosynthetic activity led to the
      evolution of aerobic respiration and responses to the resulting reactive oxygen
      species. In Rhodobacter sphaeroides, a photosynthetic alpha-proteobacterium, a
      transcriptional response to the reactive oxygen species singlet oxygen ((1)O(2))
      is controlled by the group IV sigma factor sigma(E) and the anti-sigma factor
      ChrR. In this study, we integrated various large datasets to identify genes
      within the (1)O(2) stress response that contain sigma(E)-dependent promoters both
      within R. sphaeroides and across the bacterial phylogeny. Transcript pattern
      clustering and a sigma(E)-binding sequence model were used to predict candidate
      promoters that respond to (1)O(2) stress in R. sphaeroides. These candidate
      promoters were experimentally validated to nine R. sphaeroides sigma(E)-dependent
      promoters that control the transcription of 15 (1)O(2)-activated genes. Knowledge
      of the R. sphaeroides response to (1)O(2) and its regulator sigma(E)-ChrR was
      combined with large-scale phylogenetic and sequence analyses to predict the
      existence of a core set of approximately eight conserved sigma(E)-dependent genes
      in alpha-proteobacteria and gamma-proteobacteria. The bacteria predicted to
      contain this conserved response to (1)O(2) include photosynthetic species, as
      well as free-living and symbiotic/pathogenic nonphotosynthetic species. Our
      analysis also predicts that the response to (1)O(2) evolved within the time frame
      of the accumulation of atmospheric molecular oxygen on this planet.

PMID- 18723029
TI  - Length of the hypermutation motif DGYW/WRCH in the focus of statistical limits.
      Implications for a double-motif or extended motif recognition models.
AB  - The motif DGYW/WRCH (Mh) and its frequently discussed simplified derivative
      GYW/WRC (Mhs) are involved in immunoglobulin (Ig) hypermutation. Both these
      motifs appear to be markedly shorter than the corresponding conventionally
      predicted minima of valid sequence lengths (MVSL). The same conclusion concerning
      both Mh and Mhs can also be obtained in the combined case including a less strict
      semi-empirically defined w-value and one nucleotide length tolerance related to
      MVSL. Such disagreement indicates considerably low information content in Mh and
      Mhs when evaluating these motifs as alphabetical structures (words). This fact
      raises a question of actually recognized structures (presumably longer than Mh
      and Mhs). Interestingly, both Mh and Mhs dimers or pairs of closely located Mh or
      Mhs achieve confirmation of length validity in the case of w=0.05, suggesting
      thus double-motif recognition as one of statistically consistent explanations.
      This possibility is also in agreement with the results of our model sequence
      study of mRNA derived from variable Ig gene sequences (rIgV) with respect to the
      most frequently occurring structures formed by motif overlaps in all model
      sequence sets. On the other hand, additional superior occurrence of motif pairs
      at a structurally important distance of a single DNA thread was found in the
      conserved domain (cd00099) related sequences of Elasmobranchii origin and less
      markedly in the corresponding human rIgV, but not in a randomly selected human
      subset of rIgV. The data are discussed with respect to statistical evaluation and
      structural properties of hypermutation motifs or the competent enzyme, i.e.
      activation-induced cytidine deaminase.

PMID- 18723030
TI  - Evolutionary dynamics of redundant regulatory control.
AB  - Many complex regulatory processes concern tracking a constant or variable set
      point. Examples include temperature homeostasis, rhythmic oscillation, and the
      concentration of key metabolites and enzymes. Control over homeostatic or
      tracking phenotypes often depends on multiple, overlapping regulatory systems. In
      this paper, I develop a theory for the evolutionary dynamics of redundant
      regulatory control architecture. Prior theories analyzed the evolution of
      redundant control architectures by the balance between improved performance for
      additional redundant control weighed against the decay by germline mutation that
      arises in characters with overlapping function. By contrast, I argue that
      germline mutation is likely to be a very weak balancing force in evolutionary
      dynamics. Instead, I analyze the evolutionary dynamics of redundant control by a
      balance between the benefits of reduced tracking error and the costs of building
      and running the multiple control systems. In one particular mathematical model
      that highlights key features of evolutionary dynamics, additional redundant
      control reduces tracking error multiplicatively but contributes to costs
      additively. In that model, the performance landscape has multiple peaks of the
      same height, one peak for each level of redundancy and the associated optimal
      investment per control structure. The multipeak landscape imposes evolutionary
      stasis, in which control systems resist invasion by increased or decreased levels
      of redundancy. However, fluctuating environments likely favor a rise in
      redundancy over time. With greater redundancy, investment per individual control
      structure declines, causing a decay in the performance of each individual
      dimension of control. I conclude that the costs of control structures may
      influence regulatory architecture.

PMID- 18723031
TI  - Comparison of global DNA methylation profiles in replicative versus premature
      senescence.
AB  - DNA methylation is considered to play an essential role in cellular senescence.
      To uncover the mechanism underlying cellular senescence, we established the model
      of premature senescence induced by hydrogen peroxide (H(2)O(2)) in human
      embryonic lung fibroblasts and investigated the changes of genome methylation,
      DNA methyltransferases (DNMTs) and DNA-binding domain proteins (MBDs) in
      comparison with those observed during normal replicative senescence. We found
      that premature senescence triggered by H(2)O(2) exhibited distinct morphological
      characteristics and proliferative capacity which were similar to those of
      replicative senescence. The genome methylation level decreased gradually during
      the premature as well as replicative senescence, which was associated with the
      reduction in the expression of DNMT1, reflecting global hypomethylation as a
      distinct feature of senescent cells. The levels of DNMT3b and methyl-CpG binding
      protein 2 (MeCP2) increased in both mid-aged and replicative senescent cells,
      while DNMT3a and MBD2 were upregulated in the mid-aged cells. Only DNMT3b was
      elevated in the cells in the premature senescence persistence status.
      Additionally, the expression for DNMTs, MBD2 and MeCP2 was increased rapidly upon
      H(2)O(2) treatment. These results indicate that H(2)O(2)-induced premature
      senescence share some features of replicative senescence, such as basic
      biological characteristics and global hypomethylation while there are slight
      differences in the profile of methylation-associated enzyme expression. Oxidative
      damage may hence be a causative factor in epigenetic alteration partly
      responsible for cellular senescence.

PMID- 18723032
TI  - Epigenetic mechanisms of facioscapulohumeral muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) seems to be caused by a complex
      epigenetic disease mechanism as a result of contraction of the polymorphic
      macrosatellite repeat D4Z4 on chromosome 4qter. Currently, the exact mechanism
      causing the FSHD phenotype is still not elucidated. In this review, we discuss
      the genetic and epigenetic changes observed in patients with FSHD and the
      possible disease mechanisms that may be associated with FSHD pathogenesis.

PMID- 18723033
TI  - Roles of the EZH2 histone methyltransferase in cancer epigenetics.
AB  - EZH2 is the catalytic subunit of Polycomb repressive complex 2 (PRC2), which is a
      highly conserved histone methyltransferase that targets lysine-27 of histone H3.
      This methylated H3-K27 chromatin mark is commonly associated with silencing of
      differentiation genes in organisms ranging from plants to flies to humans.
      Studies on human tumors show that EZH2 is frequently over-expressed in a wide
      variety of cancerous tissue types, including prostate and breast. Although the
      mechanistic contributions of EZH2 to cancer progression are not yet determined,
      functional links between EZH2-mediated histone methylation and DNA methylation
      suggest partnership with the gene silencing machinery implicated in tumor
      suppressor loss. Here we review the basic molecular biology of EZH2 and the
      findings that implicate EZH2 in different cancers. We also discuss EZH2
      connections to other silencing enzymes, such as DNA methyltransferases and
      histone deacetylases, and we consider progress on deciphering mechanistic
      consequences of EZH2 overabundance and its potential roles in tumorigenesis.
      Finally, we review recent findings that link EZH2 roles in stem cells and cancer,
      and we consider prospects for integrating EZH2 blockade into strategies for
      developing epigenetic therapies.

PMID- 18723035
TI  - Repeated cannabinoid injections into the rat periaqueductal gray enhance
      subsequent morphine antinociception.
AB  - Cannabinoids and opiates inhibit pain, in part, by activating the periaqueductal
      gray (PAG). Evidence suggests this activation occurs through distinct mechanisms.
      If the antinociceptive mechanisms are distinct, then cross-tolerance between
      opioids and cannabinoids should not develop. This hypothesis was tested by
      measuring the antinociceptive effect of microinjecting morphine into the
      ventrolateral PAG of rats pretreated with the cannabinoid HU-210 for two days.
      Male Sprague-Dawley rats were injected twice a day for two days with vehicle (0.4
      microL), morphine (5 microg/0.4 microL), HU-210 (5 microg/0.4 microL), or
      morphine combined with HU-210 into the ventrolateral PAG. Repeated injections of
      morphine caused a rightward shift in the morphine dose-response curve on Day 3
      (i.e., tolerance developed). No tolerance was evident in rats pretreated with
      morphine combined with HU-210. In rats pretreated with HU-210 alone, morphine
      antinociception was enhanced. This enhancement was blocked by pretreating rats
      with the cannabinoid receptor antagonist AM-251, and it also disappeared when
      rats were tested one week later. Acute microinjection of HU-210 into the PAG
      antagonized morphine antinociception, suggesting that HU-210-induced enhancement
      of morphine antinociception is a compensatory response. As hypothesized, there
      was no evidence of cross-tolerance between morphine and HU-210. In fact,
      cannabinoid pretreatment enhanced the antinociceptive effect of microinjecting
      morphine into the ventrolateral PAG. These findings suggest that alternating
      opioid and cannabinoid treatment could be therapeutically advantageous by
      preventing the development of tolerance and enhancing morphine antinociception.

PMID- 18723034
TI  - A psychobiological framework of the substrates that mediate nicotine use during
      adolescence.
AB  - Adolescents are especially likely to initiate tobacco use and are more vulnerable
      to long-term nicotine dependence. A unifying hypothesis is proposed based largely
      on animals studies that adolescents, as compared to adults, experience enhanced
      short-term positive and reduced aversive effects of nicotine, as well as less
      negative effects during nicotine withdrawal. Thus, during adolescence the strong
      positive effects of nicotine are inadequately balanced by negative effects that
      contribute to nicotine dependence in adults. This review provides a neural
      framework to explain developmental differences within the mesolimbic pathway
      based on the established role of dopamine in addiction. This pathway originates
      in the ventral tegmental area (VTA) and terminates in the nucleus accumbens
      (NAcc) where dopamine is increased by nicotine but decreased during withdrawal.
      During adolescence, excitatory glutamatergic systems that facilitate dopamine are
      overdeveloped, whereas inhibitory GABAergic systems are underdeveloped. Thus, it
      is hypothesized that adolescents display enhanced nicotine reward and reduced
      withdrawal via enhanced excitation and reduced inhibition of VTA cell bodies that
      release dopamine in the NAcc. Although this framework focuses on adolescents and
      adults, it may also apply to the understanding of enhanced vulnerability to
      nicotine in adults that were previously exposed to nicotine during adolescence.
      The hypothesis presented in this review suggests that the clinical diagnostic
      criteria developed for nicotine dependence in adults, based primarily on
      withdrawal, may be inappropriate during adolescence when nicotine withdrawal does
      not appear to play a major role in nicotine use. Furthermore, treatment
      strategies involving nicotine replacement may be harmful for adolescents because
      it may cause enhanced vulnerability to nicotine dependence later in adulthood.

PMID- 18723036
TI  - Diversity of vertebrate nicotinic acetylcholine receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) are pentameric neurotransmitter
      receptors. They are members of the Cys-loop family of ligand-gated ion channels
      which also include ionotropic receptors for 5-hydroxytryptamine (5-HT), gamma
      aminobutyric acid (GABA) and glycine. Nicotinic receptors are expressed in both
      the nervous system and at the neuromuscular junction and have been implicated in
      several neurological and neuromuscular disorders. In vertebrates, seventeen nAChR
      subunits have been identified (alpha1-alpha10, beta1-beta4, gamma, delta and
      epsilon) which can co-assemble to generate a diverse family of nAChR subtypes.
      This review will focus on vertebrate nAChRs and will provide an overview of the
      extent of nAChR diversity based on studies of both native and recombinant nAChRs.

PMID- 18723037
TI  - GABA A receptor subtype selectivity underlying selective anxiolytic effect of
      baicalin.
AB  - Baicalin, a naturally occurring flavonoid, was previously reported to induce
      anxiolytic-like effect devoid of sedation and myorelaxation in mice, acting
      through type A gamma-aminobutyric acid (GABA(A)) receptor benzodiazepine (BZ)
      site. The present study further expanded the behavioral pharmacology profile of
      baicalin and subtype selectivity was explored as a possible mechanism underlying
      its in vivo effects on mice. Baicalin was characterized using convulsion, memory,
      and motor function related animal tests; and its selectivity towards recombinant
      GABA(A) receptor subtypes expressed in HEK 293T cells was determined by
      radioligand binding assay and electrophysiological studies. In the picrotoxin
      induced seizure, step-through passive avoidance and rotarod tests, the
      anticonvulsant, amnesic and motor incoordination effects commonly associated with
      classical BZs were not observed when baicalin was administered at effective
      anxiolytic doses, demonstrating a separation of the anticonvulsant, amnesic and
      motor incoordination effects from the anxiolytic-like effect. Although baicalin
      exhibited higher binding affinity for the alpha1-containing GABA(A) subtype
      compared with alpha2-, alpha3-, and alpha5-containing subtypes, this was not
      statistically significant. In contrast to the classical BZ diazepam, baicalin
      showed significant preference for alpha2- and alpha3-containing subtypes compared
      to alpha1- and alpha5-containing subtypes in whole-cell patch clamp studies (P <
      0.01). Its subtype selectivity suggested that baicalin exerted its in vivo
      anxiolytic-like effect mainly through the alpha2- and alpha3-containing subtypes.
      Therefore, the present study revealed an underlying mechanism for the selective
      anxiolytic profile of baicalin, suggesting alpha2- and alpha3-containing subtypes
      were important drug targets for flavonoid-based anxiolytics.

PMID- 18723039
TI  - Maximization principles for frequency-dependent selection I: the one-locus two
      allele case.
AB  - In this article we study the one-locus two-allele version of the pairwise
      interaction model of frequency-dependent selection in discrete and continuous
      time. Our main aim is to provide necessary and sufficient conditions for the
      validity of maximization principles. We provide a systematic approach that covers
      all possible facets of the dynamical behavior of the model, and we illustrate our
      results by concrete examples. We show that the mean fitness of the population is
      nondecreasing if the interaction coefficients are symmetric and positive.
      Moreover, monotonic convergence to the set of equilibria always occurs, which is
      not true if we also consider negative interaction coefficients. For asymmetric
      interaction, we provide necessary conditions when the mean fitness is
      nondecreasing and sufficient conditions when it is not. Furthermore, in discrete
      time, we show that limit cycles cannot occur, unless some interaction
      coefficients are negative.

PMID- 18723038
TI  - Re-evaluating split-fovea processing in word recognition: a critical assessment
      of recent research.
AB  - In recent years, some researchers have proposed that a fundamental component of
      the word recognition process is that each fovea is divided precisely at its
      vertical midline and that information either side of this midline projects to
      different, contralateral hemispheres. Thus, when a word is fixated, all letters
      to the left of the point of fixation project only to the right hemisphere whereas
      all letters to the right of the point of fixation project only to the left
      hemisphere. An informed assessment of research in this area requires an accurate
      understanding of the nature of the evidence and arguments that have been used to
      develop this "split-fovea theory" of word recognition (SFT). The purpose of this
      article is to facilitate this understanding by assessing recent published support
      for SFT. In particular, we assess (i) the precision with which experiments have
      been conducted, (ii) the assumptions made about human visual ability, and (iii)
      the accuracy with which earlier research has been reported. The assessment
      reveals shortcomings and errors that are likely to impact on an accurate
      understanding of research in this area and, therefore, on an accurate
      understanding of the viability of SFT.

PMID- 18723040
TI  - The benzene metabolite trans,trans-muconaldehyde blocks gap junction
      intercellular communication by cross-linking connexin43.
AB  - Benzene is used at large volumes in many different human activities.
      Hematotoxicity and cancer-causation as a result of benzene exposure was
      recognized many years ago, but the mechanisms involved remain unclear. Aberrant
      regulation of gap junction intercellular communication (GJIC) has been linked to
      both cancer induction and interference with normal hematopoietic development. We
      have previously suggested that inhibition of GJIC may play a role in benzene
      toxicity since benzene metabolites were found to block GJIC, the ring-opened
      trans,trans-muconaldehyde (MUC) being the most potent metabolite. In the present
      work we have studied the molecular mechanisms underlying the MUC-induced
      inhibition of gap junctional communication. We show that MUC induces cross
      linking of the gap junction protein connexin43 and that this is likely to be
      responsible for the induced inhibition of GJIC, as well as the loss of connexin43
      observed in Western blots. We also show that glutaraldehyde possesses similar
      effects as MUC, and we compare the effects to that of formaldehyde. The fact that
      glutaraldehyde and formaldehyde have been associated with induction of leukemia
      as well as disturbance of hematopoiesis, strengthens the possible link between
      the effect of MUC on gap junctions, and the toxic effects of benzene.

PMID- 18723041
TI  - Bothrops jararaca venom (BjV) induces differential leukocyte accumulation in mice
      genetically selected for acute inflammatory reaction: the role of host genetic
      background on expression of adhesion molecules and release of endogenous
      mediators.
AB  - The dynamics of the local inflammatory events induced by Bothrops jararaca venom
      (BjV) inoculation in footpad of mice genetically selected for maximal (AIRmax)
      and minimal (AIRmin) acute inflammatory reactivity (AIR) was investigated. The
      BjV injection induced a marked inflammatory cell infiltrate with predominance of
      neutrophils, with increased blood cell numbers before its accumulation,
      suggesting a stimulatory action of BjV on mechanisms of cell mobilization from
      bone marrow. The process of cell migration is regulated by different cell
      adhesion molecules (CAM). Our results showed that neutrophil cells from both
      lines had the same pattern of response concerning CAMs expression, presenting the
      involvement of l-selectin, Mac-1 and PECAM-1 adhesion molecules in BjV-induced
      neutrophil accumulation. The effect of BjV on the release of pro-inflammatory
      cytokines and chemokines related with cellular migration was also studied and IL
      1beta, IL-6, TNF-alpha and MIP-2 levels could be detected after venom injection.
      The AIRmax mice were shown to be more responsive than AIRmin with respect to
      leukocyte influx, expression of MIP-2 and release of IL-1beta and IL-6. These
      results demonstrate the importance of host genetic background in the local
      response and the involvement of alleles accumulated in AIRmax mice in the
      inflammatory events induced by BjV.

PMID- 18723042
TI  - Venom of Collett's snake (Pseudechis colletti) blocks the binding of alpha
      bungarotoxin to acetylcholine receptors at chick but not human neuromuscular
      junctions: a histochemical study.
AB  - Transverse cryosections, 6-8 mum thick, were cut from unfixed biventer cervicis
      muscles of chicks and quadriceps muscles of humans, mounted on glass slides and
      incubated for 1h in either isotonic phosphate buffered saline, pH 7.3 (PBS), or
      crude venom of venom of Pseudechis colletti at concentrations between 2.1 and 210
      microgml(-1) in PBS. They were then exposed to a fluoresceine-conjugated alpha
      bungarotoxin to label ACh receptor sites. Exposure to the crude venom of P.
      colletti prevented the labelling of acetylcholine (ACh) receptors in chick muscle
      in a dose-dependant manner; at a concentration of 2.1 microgml(-1) labelling fell
      by 20% and at a concentration of 21 microgml(-1) by more than 90%. In contrast,
      exposure to the venom at concentrations as high as 210 microgml(-1) had no effect
      on receptor labelling in human skeletal muscle. The results suggest that ACh
      receptors in human skeletal muscle are relatively resistant to the
      postsynaptically active neurotoxins in the venom of P. colletti. The data explain
      the apparent anomaly that the venom blocks neuromuscular transmission in isolated
      nerve-muscle preparations of the chick whilst human subjects of envenoming bites
      by P. colletti exhibit no overt signs of neurotoxicity.

PMID- 18723043
TI  - Amino acid sequence of a kinin-releasing enzyme, KR-E-1, from the venom of
      Agkistrodon caliginosus (Kankoku-mamushi).
AB  - The amino acid sequence of a bradykinin-releasing enzyme, named KR-E-1, isolated
      from the venom of Agkistrodon caliginosus (Kankoku-mamushi) was determined by
      Edman sequencing of the peptides which was derived from digests with cyanogen
      bromide, hydroxylamine, achromobacter protease I, trypsin, V8 protease, arginine
      endopeptidase, and endoproteinase Asp-N. KR-E-1 consisted of 235 amino acids and
      showed conservation of the catalytic amino acid residues (His(57), Asp(102), and
      Ser(195)) of the chymotrypsin family of serine protease in its amino acid
      sequence. The carboxy-terminal amino acid, Phe, was determined using
      carboxypeptidase Y. This enzyme contains glucosamine and an N-linked
      glycosylation site. KR-E-1 showed 32, 31, 65, 65, and 67% sequence homology to
      human kallikrein, bovine thrombin, KN-BJ 2, elegaxobin, and elegaxobin II,
      respectively. The characteristic of structure of KR-E-1 was found to involve
      hydrophobic amino acid residues abundantly localizing in positions 1-50, with
      lysine residues abundantly localizing in positions 73-101.

PMID- 18723044
TI  - Non-linear integration of crowded orientation signals.
AB  - Crowding of oriented signals has been explained as linear, compulsory averaging
      of the signals from target and flankers [Parkes, L., Lund, J., Angelucci, A.,
      Solomon, J. A., & Morgan, M. (2001). Compulsory averaging of crowded orientation
      signals in human vision. Nature Neuroscience, 4(7), 739-744]. On the other hand,
      a comparable search task with sparse stimuli is well modeled by a 'Signed-Max'
      rule that integrates non-linearly local tilt estimates [Baldassi, S., & Verghese,
      P. (2002). Comparing integration rules in visual search. Journal of Vision, 2(8),
      559-570], as reflected by the bimodality of the distributions of reported tilts
      in a magnitude matching task [Baldassi, S., Megna, N., & Burr, D. C. (2006).
      Visual clutter causes high-magnitude errors. PLoS Biology, 4(3), e56]. This study
      compares the two models in the context of crowding by using a magnitude matching
      task, to measure distributions of perceived target angles and a localization
      task, to probe the degree of access to local information. Response distributions
      were bimodal, implying uncertainty, only in the presence of abutting flankers.
      Localization of the target is relatively preserved but it quantitatively falls in
      between the predictions of the two models, possibly suggesting local averaging
      followed by a max operation. This challenges the notion of global averaging and
      suggests some conscious access to local orientation estimates.

PMID- 18723045
TI  - Saccade trajectory deviations and inhibition-of-return: Measuring the amount of
      attentional processing.
AB  - This study used a classic exogenous cueing task in which an abrupt onset cue
      indicated the target location at chance level. When there was a delay between the
      cue and the target, observers responded slower and less accurate to the target
      presented at cued than at uncued locations, signifying the occurrence of
      inhibition-of-return (IOR). On some trials, instead of a manual response,
      participants had to move their eyes to a location in space. Our findings show no
      saccade deviation away from the location that was inhibited due to IOR unless
      participants had to process the target letter presented at the inhibited
      location. Our findings are consistent with the notion that inhibition resulting
      in IOR does not occur at the saccade map level but IOR seems to reduce the input
      of signals going into the saccade map. We show that the strength of saccade
      deviation is an important measure which can reveal the amount of attentional
      processing taking place at any particular location in time.

PMID- 18723046
TI  - Brief presentations reveal the temporal dynamics of brightness induction and
      White's illusion.
AB  - We measured the timecourse of brightness processing by briefly presenting
      brightness illusions and then masking them. Brightness induction (brightness
      contrast) was visible when presented for only 58 ms, was stronger at short
      presentation times, and its visibility did not depend on spatial frequency. We
      also found that White's illusion was visible at 82 ms. Together, these results
      suggest that (1) brightness perception depends on the surrounding context, even
      at very short presentation times, (2) the initial brightness percept is generated
      very quickly, but additional exposure can modulate it, and (3) the temporal
      dynamics are not dependent on a slow filling-in process.

PMID- 18723047
TI  - The effect of background spatial contrast on electroretinographic responses in
      the human retina.
AB  - The electroretinogram (ERG) was obtained to contrast modulation (CM). This
      stimulus is a product of temporal modulation of the contrast of a spatial
      sinusoid at constant mean luminance. Mean contrast (10-40%), and modulation depth
      (25-1.0) were modulated at 7.5Hz to record the pattern electroretinogram (PERG).
      The spatial pattern was a foveally fixated grating pattern with sinusoidal
      luminance profile with spatial frequency of 4.6c/deg. CM resulted in significant
      first and second harmonic ERG responses. First harmonic amplitude increases then
      flattens as a function of mean contrast with DeltaC=constant, while the second
      harmonic response remains unaffected by mean contrast. Apparently the first
      harmonic represents summed signals of local luminance responses arising from on
      and off neurons. Mean spatial contrast signals modulate preganglionic local
      luminance responses.

PMID- 18723048
TI  - The place for routine mammography screening, commencing at age 40.

PMID- 18723049
TI  - Repeated rat exposure inhibits the circadian activity patterns of C57BL/6J mice
      in the home cage.
AB  - Exposing male C57BL/6J mice repeatedly, in an unpredictable and uncontrollable
      fashion to rats, alters their cognitive performance and the neuroendocrine stress
      response, weeks to months after the rat stress. Continuous observation of the
      behavioural activity of male C57BL/6J mice in their home cage before (baseline)
      and after rat exposure could reveal if repeated rat exposure leads to changes in
      circadian activity patterns, which is a key feature of chronic stress and stress
      related disorders in humans. Rat stress (1) decreased exploratory and foraging
      activity as characterized by increased time spent in the shelter and less time in
      the open area; (2) reduced sucrose consumption and inhibited the development of
      sucrose preference, suggesting changes in the reward system and (3) the
      exploration pattern in a novel environment included more behavioural
      perseverations, but no change in general locomotor activity. Comparison to
      baseline activity pattern, i.e., before any intervention, revealed that already
      the control procedure to rat exposure (spending the same amount of time in
      another cage) disrupted the organization of behavioural activity patterns, albeit
      to a different and lesser degree than observed in rat stressed mice. While only
      the longitudinal design of the study allowed detecting these dynamic patterns of
      circadian activities, the distinct behavioural changes in foraging and
      explorative activities support our notion that repeated rat exposure might serve
      as mouse model of chronic stress.

PMID- 18723050
TI  - Ex vivo study of 5-HT(1A) and 5-HT(7) receptor agonists and antagonists on cAMP
      accumulation during memory formation and amnesia.
AB  - The cyclic adenosine monophosphate (cAMP) is a second messenger and a central
      component of intracellular signaling pathways that regulate a wide range of
      biological functions, including memory. Hence, in this work, firstly the time
      course of memory formation was determined in an autoshaping learning task, which
      had allowed the identification of testing times for increases or decreases in
      performance. Next, untrained, trained and overtrained groups were compared in
      cAMP production. Moreover, selective stimulation and antagonism of 5-HT(1A) and 5
      HT(7) receptors during memory formation and cAMP production were determined.
      Finally, since there is scarce information about how pharmacological models of
      amnesia affect cAMP production, the cholinergic or glutamatergic antagonists,
      scopolamine and dizocilpine, were tested. The major findings of this work showed
      that when the time-course was determined inasmuch as training and testing
      sessions occurred, memory performance was graduate and progressive. Notably, for
      the fourth to seventh (i.e., 48-120 h following autoshaping training session)
      testing session performance was significantly higher from the previous ones. When
      animals received 5-HT(1A) and 5-HT(7) receptor agonists and antagonists or
      amnesic drugs significant increases or decrements in memory performance were
      observed at 24 and 48 h. Moreover, when ex vivo cAMP production from trained and
      overtrained groups were compared to untrained ones, significant differences were
      observed among groups and brain areas. Trained animals treated with 8-OHDPAT,
      AS19, 8-OHDPAT plus AS19, WAY100635, SB-269970, scopolamine or dizocilpine were
      compared to similar untrained groups, and eightfold-reduced cAMP production was
      evident, showing the importance of cAMP production in the signaling case in
      mammalian memory formation.

PMID- 18723051
TI  - A toolbox facilitating stable transfection of Eimeria species.
AB  - Stable transfection of Eimeria species has been difficult to achieve because of
      the obligate requirement for in vivo amplification and selection of the
      parasites. Strategies to generate and stabilise populations of transfected
      Eimeria tenella are described here, together with the identification of optimal
      parameters for the transfection process. A series of plasmids expressing
      selectable markers, including a panel of fluorescent reporter genes and a mutant
      Toxoplasma gondii dihydrofolate reductase-thymidylate synthase (DHFR-TSm2m3) gene
      that confers resistance to pyrimethamine, were electroporated into sporozoites of
      the E. tenella Wisconsin strain and stabilised by selective passage through
      chickens. Very high transfection efficiencies of up to 25% sporozoites in
      transient transfection and up to 9% oocysts following a single round of in vivo
      selection were achieved. Crucial factors include the use of very freshly
      harvested parasites with the AMAXA nucleofection system (program U33 in a cytomix
      buffered reaction) and linearised plasmid DNA. The use of a restriction enzyme
      mediated integration (REMI) protocol boosted overall efficiency and elevated
      insertion rate per genome. Successful development of methods to generate and
      isolate stable populations of transfected Eimeria parasites will now stimulate
      rapid expansion of reverse genetic studies in this important coccidian.

PMID- 18723052
TI  - Angiotensin II upregulates renin-angiotensin system in human isolated T
      lymphocytes.
AB  - This study was aimed at investigating the effects of Angiotensin (Ang) II
      stimulation on T lymphocytes mRNA expression of angiotensinogen (AGTN),
      angiotensin-converting enzyme (ACE) and AT1-receptor (R) and on ACE activity and
      Ang II content. The effects of Ang II stimulus were studied in lipopolysaccharide
      (LPS)-stimulated or not stimulated lymphocytes. mRNA expression for interferon
      gamma (INF-gamma) was also studied to investigate whether a link between
      lymphocyte RAS and immunological function might occur. mRNAs for AGTN, ACE and
      AT1-R were obtained from peripheral blood of 18 healthy subjects and were
      quantified by real time quantitative transcriptase-polymerase chain reaction
      (PCR). ACE activity was assayed in cell pellets and supernatants by measuring the
      hippuric acid formation by high performance liquid chromatography (HPLC) and Ang
      II cell content was measured by radioimmunoassay (RIA) after HPLC separation. All
      determination were performed under baseline conditions and after the addition of
      10(e- 13) M Ang II to LPS-stimulated or unstimulated lymphocytes. Ang II caused a
      significant upregulation of T subset lymphocytes gene expression of ACE and AT1-R
      and of INF gamma, and a marked increase in ACE activity and cell Ang II
      concentration. AGTN gene was never expressed. All these effects were further
      enhanced in T lymphocytes presitmulated by LPS and completely inhibited by
      Irbesartan. Our findings strongly support the evidence of a positive Ang II
      driven autocrine loop that upregulates cell RAS of isolated lymphocytes and
      activates the immuno response. The immuno-potentiating effect of Ang II,
      specifically shown in T subset, can be deleterious when local RAS are
      disregulated as in cardiovascular atherosclerotic disease.

PMID- 18723053
TI  - Macromolecular crowding and its potential impact on nuclear function.
AB  - It is well established, that biochemical reactions are dependent on pH, ionic
      strength, temperature and the concentration of reactants. However, the steric
      repulsion among bulky components of biological systems also affect biochemical
      behavior: The 'excluded volume effect of macromolecular crowding' drives bulky
      components into structurally compact organizations, increases their thermodynamic
      activities and slows down diffusion. The very special composition of the cell
      nucleus, which is packed with high-molecular chromatin, ribonucleo-particles and
      associated proteins, suggests that crowding-effects are part of nuclear
      functionality. Realizing that many nuclear processes, notably gene transcription,
      hnRNA splicing and DNA replication, use macromolecular machines, and taking into
      account that macromolecular crowding provides a cooperative momentum for the
      assembly of macromolecular complexes, we here elaborate why macromolecular
      crowding may be functionally important in supporting the statistical significance
      of nuclear activities.

PMID- 18723054
TI  - Electrical autonomic correlates of emotion.
AB  - This paper focussed on how electrophysiological autonomic data may contribute to
      better understand neural substrates of emotional processing. The utility of
      autonomic electrophysiological markers for assessing emotional and cognitive
      processes is presented in the context of an important bodily arousal interface.
      Components of general autonomic control are reviewed and relevant neural
      modulations of specific autonomic variables were discussed. The role of autonomic
      feedback on central processes is emphasized and neural influences on autonomic
      activities as an index of arousal dimension, the electrodermal activity (EDA),
      are outlined. An overview of brain mechanisms governing generation and control of
      EDA is presented, and the contribution of electrodermal parameters as indices of
      emotional activation illustrated by data related to diurnal emotional reactivity
      and to non consciously subjective emotionality. Conclusions highlight the role of
      electrical autonomic expressions as tools to explore emotional components of mind
      body-mind relationships.

PMID- 18723055
TI  - The protection of Bcl-2 overexpression on rat cortical neuronal injury caused by
      analogous ischemia/reperfusion in vitro.
AB  - Recent studies have suggested that neuronal apoptosis in cerebral ischemia could
      arise from dysfunction of endoplasmic reticulum (ER) and mitochondria. B-cell
      lymphoma/leukemia-2 gene (Bcl-2) has been described as an inhibitor both in
      programmed cell death (PCD) and ER dysfunction during apoptosis, and the Bcl-2
      family play a key role in regulating the PCD, both locally at the ER and from a
      distance at the mitochondrial membrane. However, its signal pathways and concrete
      mechanisms in endoplasmic reticulum-initiated apoptosis remain incompletely
      understood. We therefore investigate whether ischemia/reperfusion (I/R) causes
      neuronal apoptosis in part via cross-talk between ER and mitochondria or not, and
      how the overexpression of Bcl-2 prevents this form of cell death. Here we show
      that analogous I/R-induced cell death occurs consequent to interactions of ER
      stress and mitochondrial death pathways. The participation of the mitochondrial
      pathway was demonstrated by the release of cytochrome C (cyt C) from
      mitochondrial into cytoplasmic fractions and caspase-9 cleavage. The involvement
      of ER stress was further supported by the observable increase of glucose
      regulated protein 78(GRP78)/BiP expression and caspase-12 activity. Furthermore,
      prior to these changes, swelling of the ER lumen and dissociation of ribosomes
      from rough ER were detected by electron microscopy. Bcl-2 overexpression inhibits
      the release of cyt C and the activation of caspase-9/-8/-3 but not caspase-12
      based on the results of Western blot. These suggest that cross-talk between ER
      and mitochondria participate in neuronal damage after ischemia/reperfusion. Bcl-2
      overexpression could suppress I/R-induced neuronal apoptosis via influencing
      mitochondrial integrity.

PMID- 18723056
TI  - Characterization of the interaction of domain III of the envelope protein of
      dengue virus with putative receptors from CHO cells.
AB  - Domain III (DIII) of the envelope protein of dengue virus (DENV) contains
      structural determinants for the interaction with cellular receptors. In the
      present study a solid phase assay and recombinant fusion proteins containing DENV
      DIII of serotypes 1 and 2 were used to study structural features of the
      interaction of the envelope protein with putative receptors present in the
      microsomal fraction of CHO cells. Recombinant fusion proteins showed specific
      interaction with proteins present in the microsomal fraction. Binding of the
      fusion proteins across the pH range of 5.5-8.0 resembled that of virus particles,
      peaking at pH 6.0. This suggests that the interaction of DIII with cell
      receptor(s) is strengthened at endosomal pH. The effect of reduction and
      carbamidomethylation of cysteine residues on the binding to the microsomal
      fraction and in their recognition by antibodies suggests that the region of DIII
      that is interacting with putative receptor(s) overlaps only partially with a
      dominant epitope of the antibody response. The analysis of the residue
      conservation profile indicates that the surface of DIII is composed typically of
      specific sub-complex residues with an increased representation of specific
      type/subtype residues found at the surface that closely correlates with the
      dominant neutralizing epitope.

PMID- 18723057
TI  - Development of chitosan-SLN microparticles for chemotherapy: in vitro approach
      through efflux-transporter modulation.
AB  - Drug efflux-transporters serve as a major barrier to anticancer drugs at the
      target site. One strategy to enhance the therapeutic efficacy of drugs against
      cancer is to increase their available concentrations at the target site by
      suppressing or modulating efflux-transporters. This manuscript deals with the
      development and evaluation of the particle type drug delivery system made of
      stearic acid (Solid Lipid Nanoparticle - SLN) and chitosan for the delivery of
      Phenethyl Isothiocyanate (PEITC), a tumor-suppressive agent, through the
      pulmonary route. The rationale behind the particle type drug delivery system
      involves a prior release of the efflux-transporter inhibitors, such as tamoxifen,
      verapamil HCl or nifedipine, to suppress or modulate the efflux activity of ABC
      transporters followed by the release of the efflux-transporter substrate, PEITC.
      The efficacy of Chitosan-SLN Microparticles (CSM) as a carrier for PEITC was
      evaluated by investigating the release profiles of PEITC loaded in CSM and its
      cytotoxicity in the presence or absence of the efflux-transporter inhibitors. An
      initial burst release of the inhibitors, followed by gradual, sustained release
      of PEITC and subsequent increase in cytotoxicity was observed. This finding
      indicated that the efflux transporter inhibitors significantly affected the PEITC
      uptake rate by Calu-3 cells. Judging from these results, CSM can be an efficient
      drug delivery system for the substrates susceptible to the efflux-transporters.

PMID- 18723058
TI  - The dual pathway model of overeating. Replication and extension with actual food
      consumption.
AB  - van Strien et al. [van Strien, T., Engels, R. C. M. E., van Leeuwe, J., Snoek, H.
      M. (2005). The Stice model of overeating: tests in clinical and non-clinical
      samples. Appetite, 45, 205-213] extended the negative affect pathway of Stice's
      dual pathway model of overeating Stice [Stice, E. (1994). Review of the evidence
      for a sociocultural model of bulimia nervosa and an exploration of the mechanisms
      of action. Clinical Psychology Review, 14(7), 633-661] successfully with the
      variables lack of interoceptive awareness and emotional eating. This study aimed
      to replicate these findings in a sample of female college students with food
      consumption as the measure for overeating. Structural equation modeling was used
      to test the original and the extended model and both models fitted. In the
      extended model, the relation between negative affect and consumption seemed to
      run only via lack of interoceptive awareness and emotional eating.

PMID- 18723059
TI  - Antimicrobial peptides from the venoms of Vespa bicolor Fabricius.
AB  - Hornets possess highly toxic venoms, which are rich in toxins, enzymes and
      biologically active peptides. Many bioactive substances have been identified from
      wasp venoms. Vespa mastoparan (MP-VBs) and Vespa chemotatic peptide presenting
      antimicrobial action (VESP-VBs) were purified and characterized from the venom of
      the wasp, Vespa bicolor Fabricius. The precursors encoding VESP-VBs and MP-VBs
      were cloned from the cDNA library of the venomous glands. Analyzed by FAB-MS, the
      amino acid sequence and molecular mass for VESP-VB1 were FMPIIGRLMSGSL and
      1420.6, for MP-VB1 were INMKASAAVAKKLL and 1456.5, respectively. The primary
      structures of these peptides are homologous to those of chemotactic peptides and
      mastoparans isolated from other vespid venoms. These peptides showed strong
      antimicrobial activities against bacteria and fungi and induced mast cell
      degranulation, but displayed almost no hemolytic activity towards human blood red
      cells.

PMID- 18723060
TI  - The role of CD8 suppressors versus destructors in autoimmune central nervous
      system inflammation.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
      nervous system (CNS) of putative autoimmune origin. Recent evidence indicates
      that MS autoimmunity is linked to defects in regulatory T-cell function, which
      normally regulates immune responses to self-antigens and prevents autoimmune
      diseases. MS and its animal model, experimental autoimmune encephalomyelitis
      (EAE), have long been regarded as a CD4(+) T-cell-mediated autoimmune disease.
      Studies addressing the role of CD8(+) T cells, however, have only recently begun
      to emerge. Pathogenic function was attributed to CD8(+) T cells because of their
      abundant presence or oligoclonal repertoire within MS lesions. However, CD8(+) T
      cells appeared to have important regulatory functions, as demonstrated in EAE or
      human MS studies. We here review the contribution of CD8(+) T cells to
      inflammation and immune regulation in CNS autoimmunity. The knowledge of distinct
      CD8(+) T-cell populations exerting destructive versus beneficial functions is
      summarized. The long-term goal is to delineate the exact phenotypic and
      functional characteristics of regulatory CD8(+) T-cell populations (natural as
      well as inducible) in humans. This knowledge may help to further develop concepts
      of reconstituting or enhancing endogenous mechanisms of immune tolerance in
      future therapeutic concepts for MS.

PMID- 18723062
TI  - Economic evaluation of varicella vaccination in Italian children and adolescents
      according to different intervention strategies: the burden of uncomplicated
      hospitalised cases.
AB  - An economic evaluation of universal varicella vaccination in Italy was performed
      to assess the potential clinical and economic effects of three different
      strategies versus no vaccination. By means of the EVITA model, vaccination with
      two doses in toddlers only (1-1.5 years), adolescents only (13 years) and
      toddlers with adolescents catch-up programmes were simulated. All universal
      varicella vaccination strategies including toddlers (with or without an
      adolescent catch-up programme) turned out to be highly effective in reducing the
      burden of disease due to varicella. In addition, they lead to significant net
      savings from the societal perspective but to higher costs compared to return of
      investment from National Health Service perspective. The huge economic burden of
      hospitalised uncomplicated varicella cases registered in Italy can partially
      explain these highly beneficial findings for the societal perspective. Overall,
      our analysis confirmed the favourable clinical and economic impact of routine
      varicella vaccination with two doses of vaccine in Italy.

PMID- 18723061
TI  - Influenza-induced expression of functional tumor necrosis factor-related
      apoptosis-inducing ligand on human peripheral blood mononuclear cells.
AB  - The immunologic response to influenza virus infection, like many other viruses,
      is characterized by robust production of proinflammatory cytokines, including
      type I and II interferon (IFN), which induce a number of antiviral effects and
      are essential for priming the innate and adaptive cellular components of the
      immune response. Here, we demonstrate that influenza virus infection induces the
      expression of functional tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) on human peripheral blood mononuclear cell (PBMC) populations. Consistent
      with previous studies examining TRAIL upregulation, increased TRAIL expression
      correlated with increased type I and II IFN levels in PBMC cultures.
      Interestingly, dilution of these cytokines resulted in decreased expression of
      TRAIL. TRAIL upregulation was not dependent on active viral infection, and TRAIL
      was observed on NS-1-negative cells. Furthermore, influenza virus infection of
      lung adenocarcinoma cells (A549) resulted in increased sensitization to TRAIL
      induced apoptosis compared with uninfected A549. Infected PBMC expressing TRAIL
      preferentially killed infected A549, but did not affect uninfected cells, and the
      addition of soluble TRAIL-R2:Fc blocked the lysis of infected cells,
      demonstrating TRAIL-dependent killing of infected cells. Collectively, these data
      demonstrate that TRAIL expression is induced on primary human innate and adaptive
      immune cells in response to cytokines produced during influenza infection and
      that TRAIL sensitivity is increased in influenza virus-infected cells. These data
      also suggest that TRAIL is a primary mechanism used by influenza-stimulated human
      PBMC to kill influenza-infected target cells and reinforce the importance of
      cytokines produced in response to TLR agonists in enhancing cellular immune
      effector functions.

PMID- 18723063
TI  - Monitoring vaccine safety using case series cumulative sum charts.
AB  - We adapt the self-controlled case series method for routine surveillance of
      vaccine safety using cumulative sum (CUSUM) charts. The CUSUM surveillance method
      we propose is applicable for detecting associations that arise in a short pre
      determined risk period following vaccination. The performance of the case series
      CUSUM is investigated through simulations. We illustrate the method using
      retrospective analyses of influenza vaccine and Bell's palsy, and MMR vaccine and
      febrile convulsions.

PMID- 18723065
TI  - The effect of Bacille Calmette-Guerin vaccine on tuberculin reactivity in
      indigenous children from communities with high prevalence of tuberculosis.
AB  - The Bacille Calmette-Guerin (BCG) vaccine is the most widely used vaccine in the
      world, however it may cause problems for the appropriate interpretation of the
      tuberculin skin test (TST). We assessed the diagnostic value of latent infection
      in vaccinated and unvaccinated indigenous children from communities that have a
      very high prevalence of adult tuberculosis (TB). A total of 997 children under 15
      years old and classified in age groups (0-1.9, 2-5, 6-9 and 10-15 years old) were
      randomly selected and given TSTs using the Mantoux technique. TST induration
      values of vaccinated children (n=724) were compared with those of children
      unvaccinated (n=273). BCG vaccination was not an important cause of false
      positive TST, except in communities with a low prevalence of active TB. In
      conclusion, the results suggested that a history of BCG vaccination on TST+
      response after 10 years of vaccination was statistically insignificant but
      whether at earlier age TST+ reflects most probably the degree of exposure to TB
      cases than BCG vaccination should be clarified in the future.

PMID- 18723064
TI  - Protective efficacy of a recombinant subunit West Nile virus vaccine in domestic
      geese (Anser anser).
AB  - Introduction of the West Nile virus (WNV) to Hawai'i will undoubtedly devastate
      many populations of critically endangered avian species indigenous to Hawai'i.
      The protective efficacy of a protein-based WNV subunit vaccine formulated with
      adjuvant was evaluated in domestic geese as a surrogate species for the
      endangered Nene, the state bird of Hawai'i. Prevention of viremia following viral
      infection of vaccinated birds was used as the clinical endpoint of protection.
      ELISA and plaque reduction neutralization tests demonstrate that significant
      levels of vaccine antigen-specific antibody were produced in groups of birds
      vaccinated with 5 or 10 microg of the WN-80E antigen formulated with ISA720
      adjuvant. Moreover, after challenge with WNV, no viremia was detected in
      vaccinated birds, whereas viremia was detected up to 4 days after and virus was
      detected by oral swab for 6 days after infection among control groups. Safe and
      effective vaccination of managed or captive endangered bird populations will
      protect species with critically low numbers that could not survive the added
      mortality of introduced disease.

PMID- 18723066
TI  - The relationship between pertussis symptomatology, incidence and serology in
      adolescents.
AB  - Adolescents have an unknown true incidence of pertussis and are important
      reservoirs of transmission. We evaluated the incidence of coughing illnesses,
      serologic evidence of recent infection and the relationship between
      symptomatology and serology in adolescents. A retrospective respiratory
      questionnaire and anti-pertussis toxin immunoglobulin G measurement was
      undertaken in a convenience sample of adolescents and was repeated one year
      later. The US Centers for Disease Control clinical case definition of pertussis
      was used. At least a third of coughing illnesses met the CDC clinical case
      definition. Symptoms correlated with serology. Pertussis was endemic with a high
      annual incidence of new infections.

PMID- 18723067
TI  - The enhanced anti-angiogenic and antitumor effects of combining flk1-based DNA
      vaccine and IP-10.
AB  - The purpose of the present study was to evaluate the anti-vasculature effects and
      the anti-tumor effects of attenuated Salmonella typhimurium vaccine strain
      encoding murine vascular endothelial growth factor (VEGF) receptor-2 (flk1) in
      combination with plasmid DNA vector encoding the murine interferon-induced
      protein of 10kDa (IP-10 or CXCL10) gene. Mouse models of malignant melanoma (B16
      F10) were treated with combining orally given attenuated S. typhimurium vaccine
      strain encoding flk1 with direct intratumoral injection of a non-viral plasmid
      DNA vector encoding the murine IP-10 gene. The volumes of tumors and survival of
      mice bearing B16-F10 tumors were observed. Cytolytic T lymphocyte (CTL) response
      was measured by cytotoxic assay, vessel density and tumor-cell proliferation were
      observed by immunostaining, and tumor apoptosis was determined by TUNEL staining.
      The results revealed the combination therapy groups showed more significantly
      inhibited tumor growth, apoptosis of tumor cells, and reduced neovascularization,
      cell proliferation, and developed a strong CTL response in these mice. In
      summary, the therapy of attenuated S. typhimurium vaccine strain encoding flk1
      combined with the IP-10 gene has significant synergistic effect against tumors.

PMID- 18723068
TI  - Cost-effectiveness of human papillomavirus vaccine in reducing the risk of
      cervical cancer in Ireland due to HPV types 16 and 18 using a transmission
      dynamic model.
AB  - We evaluated the cost-effectiveness of combining a cervical cancer screening
      programme with a national HPV vaccination programme compared to a screening
      programme alone to prevent cervical dysplasia and cervical cancer related to HPV
      types 16 and 18 in the Irish healthcare setting. The incremental cost
      effectiveness of vaccination strategies for 12-year-old females (base-case) and
      12-26-year-old catch-up vaccination strategies were examined. The base-case
      incremental cost-effectiveness ratio was euro17,383/LYG. Using a probabilistic
      sensitivity analysis about the base-case, the 95% CI for cost per LYG was
      (euro3400 to euro38,400). This suggests that vaccination against HPV types 16 and
      18 would be cost-effective from the perspective of the Irish healthcare payer.

PMID- 18723069
TI  - Evaluation of a positive marker of avian influenza vaccination in ducks for use
      in H5N1 surveillance.
AB  - Control measures for H5N1 avian influenza involve increased biosecurity,
      monitoring, surveillance and vaccination. Subclinical infection in farmed ducks
      is important for virus persistence. In major duck rearing countries, homologous
      H5N1 vaccines are being used in ducks, so sero-surveillance using H5- or N1
      specific antibody testing cannot identify infected flocks. An alternative is to
      include a positive marker for vaccination. Testing for an antibody response to
      the marker would confirm approved vaccine use. Concurrent testing for H5 antibody
      responses would determine levels adequate for protection or indicate recent
      infection, with an anamnestic H5 antibody response requiring further virological
      investigation. In this study, we have evaluated the use of a TT marker in ducks
      given avian influenza vaccination. Wild or domestic ducks were tested for
      antibodies against TT and all 463 ducks were negative. High levels of TT-specific
      antibodies, produced in twice-TT vaccinated Muscovy ducks, persisted out to 19
      weeks. There was no interference by inclusion of TT in an inactivated H6N2
      vaccine for H6- or TT-seroconversion. Thus TT is a highly suitable exogenous
      marker for avian influenza vaccination in ducks and allows sero-surveillance in
      countries using H5N1 vaccination.

PMID- 18723070
TI  - One-year chronic toxicity of madder color in F344 rats--induction of
      preneoplastic/neoplastic lesions in the kidney and liver.
AB  - To evaluate chronic toxicity of madder color (MC), a natural food colorant
      extracted from the roots of Rubia tinctorum L., F344 rats were fed diet
      containing 0%, 0.2%, 1.0% or 5.0% MC for 53 weeks. Hematological changes
      including anemia and serum biochemical alterations indicating hepatotoxicity were
      demonstrated at 5.0% in both sexes. Relative weights of the liver were
      significantly increased from 1.0% in both sexes, and those of the kidney were
      significantly increased from 1.0% in males and from 0.2% in females.
      Histopathologically, atypical renal tubule hyperplasias were increased at 1.0% or
      higher in both sexes in association with increase of cell proliferative activity
      in the tubules. A renal cell adenoma was observed in a male rat receiving 5.0%
      MC. In addition, glutathione S-transferase placental form-positive liver cell
      foci were significantly increased at 5.0% in both sexes. These results indicate
      that MC has chronic toxicity targeting kidney, liver and blood cells. Moreover,
      the results strongly suggest that MC may have the carcinogenic potential in the
      kidney and the liver.

PMID- 18723071
TI  - TPX2 in malignantly transformed human bronchial epithelial cells by anti
      benzo[a]pyrene-7,8-diol-9,10-epoxide.
AB  - In order to elucidate the function of the targeting protein for Xenopus kinesin
      like protein 2 (Xklp2) (TPX2) in the malignant transformation of human bronchial
      epithelial cells induced by anti-benzo[a]pyrene-trans-7, 8-dihydrodiol-9, 10
      epoxide (anti-BPDE), TPX2 was characterized in cells at both the gene and the
      protein levels. TPX2 was present at higher levels in 16HBE-C cells than in 16HBE
      cells as demonstrated by two-dimensional gel electrophoresis,
      immunocytochemistry, Western blot analysis and RT-PCR. TPX2 was also detected in
      lung squamous-cell carcinoma tissues by immunohistochemistry, but not in normal
      lung tissues. Depression of TPX2 by RNA interference in 16HBE-C cells led to a
      decrease in cell proliferation, S-phase cell cycle arrest and cell apoptosis.
      Abnormal TPX2 tyrosine phosphorylation was detected in 16HBE-C cells, and this
      could be inhibited, to different degrees, by tyrosine kinase inhibitors.
      Inhibiting tyrosine phosphorylation in 16HBE-C cells by three selected tyrosine
      protein kinase inhibitors, tyrphostin 47, AG112 and AG555, caused G(0)/G(1)-phase
      cell cycle arrest. Our results suggest that anti-BPDE can cause the over
      expression of TPX2 and its aberrant tyrosine phosphorylation. Misregulation of
      TPX2 affects the cell cycle state, proliferation rates and apoptosis.

PMID- 18723072
TI  - Positive circuits and d-dimensional spatial differentiation: application to the
      formation of sense organs in Drosophila.
AB  - We discuss a rule proposed by the biologist Thomas according to which the
      possibility for a genetic network (represented by a signed directed graph called
      a regulatory graph) to have several stable states implies the existence of a
      positive circuit. This result is already known for different models, differential
      or discrete formalism, but always with a network of genes contained in a single
      cell. Thus, we can ask about the validity of this rule for a system containing
      several cells and with intercellular genetic interactions. In this paper, we
      consider the genetic interactions between several cells located on a d
      dimensional lattice, i.e., each point of lattice represents a cell to which we
      associate the expression level of n genes contained in this cell. With this
      configuration, we show that the existence of a positive circuit is a necessary
      condition for a specific form of multistationarity, which naturally corresponds
      to spatial differentiation. We then illustrate this theorem through the example
      of the formation of sense organs in Drosophila.

PMID- 18723073
TI  - Negative cooperativity in H2 relaxin binding to a dimeric relaxin family peptide
      receptor 1.
AB  - H2 relaxin, a member of the insulin superfamily, binds to the G-protein-coupled
      receptor RXFP1 (relaxin family peptide 1), a receptor that belongs to the leucine
      rich repeat (LRR)-containing subgroup (LGRs) of class A GPCRs. We recently
      demonstrated negative cooperativity in INSL3 binding to RXFP2 and showed that
      this subgroup of GPCRs functions as constitutive dimers. In this work, we
      investigated whether the binding of H2 relaxin to RXFP1 also shows negative
      cooperativity, and whether this receptor functions as a dimer using BRET(2). Both
      binding and dissociation were temperature dependent, and the pH optimum for
      binding was pH 7.0. Our results showed that RXFP1 is a constitutive dimer with
      negative cooperativity in ligand binding, that dimerization occurs through the
      7TM domain, and that the ectodomain has a stabilizing effect on this interaction.
      Dimerization and negative cooperativity appear to be general properties of LGRs
      involved in reproduction as well as other GPCRs.

PMID- 18723074
TI  - Steroid-converting enzymes in human ovarian carcinomas.
AB  - Anti-estrogen therapies for treating ovarian carcinoma have had mixed outcomes
      suggesting some tumors may be estrogen-dependent. We assayed the activity levels
      of 17beta-hydroxysteroid dehydrogenase (17beta-HSD), 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD), 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD/3-KSR)
      and estrone sulfatase in a series of ovarian epithelial carcinomas. 17beta-HSD
      activity ratios with estradiol (E(2)) and testosterone (T), and inhibition by
      isoform-specific inhibitors were used to estimate the contributions of 17beta-HSD
      isoforms. Activity levels were highest for estrone sulfatase, followed,
      respectively by 17beta-HSD, 3alpha-HSD/3-KSR, and 3beta-HSD. E(2)/T activity
      ratios varied widely between samples. A 17beta-HSD type 1 inhibition pattern was
      observed in 23% of the samples and a type 2 pattern in 25%. E(2) formation from
      estrone sulfate (E(1)S) was detected in 98% (47/48) of the samples. 17beta-HSD
      type 1, type 2 and type 5 mRNA was detected in matched primary tumor and
      metastases. Evaluation of 17beta-HSD and sulfatase activity levels, activity
      ratios and inhibition patterns may help predict tumor response to endocrine
      therapy.

PMID- 18723075
TI  - Necroptosis contributes to the NMDA-induced excitotoxicity in rat's cultured
      cortical neurons.
AB  - Necroptosis is a newly discovered type of cell death characterized with the
      combined biochemical and ultrastructural features of necrosis and apoptosis. Nec
      1 has been reported to exhibit the selective inhibition for necroptosis, which
      has now been used as an operational definition of necroptosis. The purpose of
      this study was to evaluate whether necroptosis is involved in the NMDA-induced
      excitotoxicity and furthermore whether the elevation of intracellular Ca(2+) is
      involved in the NMDA-induced necroptosis. Our findings showed that Nec-1 (100
      micromol/L) inhibited NMDA-induced decrease of cell viability by 26% (p<0.01),
      suppressed NMDA-induced decrease of living cells by 23% (p<0.01) and attenuated
      NMDA-induced leakage of LDH by 28% (p<0.01). In addition, Nec-1 also suppressed
      NMDA-induced elevation of intracellular Ca(2+) by 36% (p<0.05). These findings
      indicated for the first time that necroptosis contributes to the NMDA-induced
      excitotoxicity, and the elevation of intracellular Ca(2+) may be one of the
      potential mechanisms underlying NMDA-induced necroptosis. Although necroptosis
      may be involved in NMDA-induced excitotoxicity, it may just constitute a small
      contribution.

PMID- 18723077
TI  - Elevated myeloperoxidase activity in white matter in multiple sclerosis.
AB  - Recent studies have revealed extensive axonal damage in patients with progressive
      multiple sclerosis (MS). Axonal damage can be caused by a plethora of factors
      including the release of proteolytic enzymes and cytotoxic oxidants by activated
      immune cells and glia within the lesion. Macrophages and microglia are known to
      express myeloperoxidase (MPO) and generate reactive oxygen species during myelin
      phagocytosis in the white matter. In the present study we have measured MPO
      levels in post-mortem homogenates of demyelinated and non-demyelinated regions of
      white matter from nine patients with MS and seven controls, and assessed MPO
      immunoreactivity within MS brain. In homogenates of MS white matter,
      demyelination was associated with significantly elevated MPO activity when
      compared to controls. Immunohistochemistry showed MPO to be expressed mainly by
      macrophages within and adjacent to plaques. Demyelination in MS is associated
      with increased activity of MPO, suggesting that this production of reactive
      oxygen species may contribute to axonal injury within plaques.

PMID- 18723076
TI  - The actin cross-linking protein AFAP120 regulates axon elongation in a tyrosine
      phosphorylation-dependent manner.
AB  - Growth cone guidance and axon elongation require the dynamic coordinated
      regulation of the actin cytoskeleton. As the growth cone moves, actin-dependent
      forces generate tension that enables protrusive activity in the periphery and
      drives growth cone translocation. This dynamic remodeling of the actin
      cytoskeleton in response to membrane tension requires activation of Src kinase.
      Although it has been proposed that these actin-dependent forces vary with the
      extent of actin cross-linking, the identity of the cross-linking protein(s)
      remains unknown. AFAP120 is a nervous system specific actin cross-linking protein
      that is regulated by Src kinase phosphorylation. Here, we report that AFAP120 is
      expressed and tyrosine phosphorylated in differentiating cerebellar granule
      cells, where it is enriched in the axon and growth cone. Over-expression of
      AFAP120 enhances neurite elongation in a tyrosine phosphorylation-dependent
      manner. These findings suggest that AFAP120 may coordinate Src signaling with the
      dynamic changes in the actin cytoskeleton that drive growth cone motility and
      axon elongation.

PMID- 18723078
TI  - Haeme oxygenase and nitric oxide synthetase blockade and brain blood flow in
      sheep exposed to carbon monoxide.
AB  - Carbon monoxide (CO) usually does not damage the brain cortex in our in vivo
      model. To investigate the possible protective role of responsive and regulated
      changes in blood flow, 24 ewes were randomly assigned in equal numbers to sham
      control, CO-control and treatment (haeme oxygenase (HO) and nitric oxide
      synthetase (NOS) inhibited) groups. Sheep in the second and third groups were
      then anaesthetised with CO for 2 h. Brain blood flow was measured using Laser
      Doppler and was increased in CO exposed sheep. The CO-induced anaesthesia was
      associated with isolated brain white matter damage. In the HO/NOS inhibited
      sheep, cortical EEG recovery after the anaesthesia was slower and incomplete, and
      cortical blood flow increased whereas white matter flow decreased. These results
      confirm our earlier findings that the induction of HO and NOS by CO inhalation is
      protective, but, suggest a relationship between tissue injury and blood flow that
      is perhaps partly causal.

PMID- 18723079
TI  - The single-prolonged stress paradigm alters both the morphology and stress
      response of magnocellular vasopressin neurons.
AB  - Vasopressin (AVP) plays an important role in anxiety-related and social
      behaviors. Single-prolonged stress (SPS) has been established as an animal acute
      severe stress model and has been shown to induce a lower adrenocorticotropic
      hormone (ACTH) response upon cortisol challenge. Here, we show results from
      immunoassays for AVP, ACTH, and corticosterone (CORT), and in situ hybridizations
      for AVP mRNA performed 7 days after SPS exposure. Immunofluorescence for AVP was
      also performed during the 7-day period following SPS exposure and after an
      additional forced swimming stress paradigm. We observed that the plasma
      concentrations of AVP, ACTH, and CORT were not altered by SPS; ACTH content in
      the pituitary and AVP mRNA expression in the supraoptic nucleus (SON) were
      significantly reduced by SPS. During the 7-day period following SPS, the
      intensity of immunoreactivity, the size of the soma, and the immunoreactive
      optical density of the dendrites of AVP neurons in the SON all increased. An
      apparent reduction in the intensity of AVP immunoreactivity was observed in the
      SON at 4 h after additional stress. Additional forced swimming led to a rapid
      increase in the dendritic AVP content only in the controls and not in the SPS
      treated rats. These findings suggest that AVP is a potential biomarker for past
      exposure to severe stress and that alterations in AVP may affect the development
      of pathogenesis in stress-related disorders.

PMID- 18723080
TI  - Enhanced stress reactivity in nitric oxide synthase type 2 mutant mice: findings
      in support of astrocytic nitrosative modulation of behavior.
AB  - Alterations of nitric oxide (NO) metabolism in the brain have been associated
      with modifications of stress-related behavior in animal models. It has been
      generally assumed that these behavioral changes are due to the neuronal
      nitrosative activity. On the other hand, glial NO production has been
      demonstrated mainly as a slow reaction to brain insults through the activity of
      an inducible nitric oxide synthase (NOS) isoform (NOS2). Recently we uncovered
      increased NOS activity in astrocytes of mice with a NOS2 mutation. Interestingly,
      these mice revealed a behavioral phenotype suggestive of increased susceptibility
      to stress. In the present study we investigated the responses of these mutants to
      stress by exposing them to predator scent. Seven days later, mutant mice
      exhibited significantly higher anxiety-like behavior in the elevated-plus maze,
      increased acoustic startle responses, and higher plasma corticosterone levels
      compared with their controls. Systemic administration of a NOS inhibitor prior to
      the stress exposure reversed these stress-related effects without affecting
      controls' behavior. These findings are in agreement with previous studies showing
      an association between increased NO levels and enhanced anxiety-like responses.
      In addition, mutant mice performed better in the Morris water maze prior to
      stress exposure, but the two animal groups performed alike in an object
      recognition test. Taken together, our results suggest the involvement of
      astrocytic-derived NO in modulating behavior.

PMID- 18723081
TI  - Comparative study on the offset responses of simple cells and complex cells in
      the primary visual cortex of the cat.
AB  - Simple and complex cells are two basic and distinct functional types of neurons
      in the mammalian primary visual cortex. Here, we studied the onset response and
      the offset response of simple and complex cells to a flashing visual stimulus in
      the cat's area 17. Compared with simple cells, complex cells exhibited greater
      similarity between the onset and offset responses in peak latency. For simple
      cells, onset response had greater peak amplitude and signal-to-noise ratio than
      offset response, and for complex cells, vice versa. For both types of cortical
      cells, the amplitude of offset responses increased with stimulus duration within
      100 ms significantly, while the onset response did not. However, to elicit a
      detectable offset response, complex cells tended to require shorter stimulus
      duration than simple cells did. In regard to the similarity of psychophysical
      data, these results suggest that the rebound offset response of cortical cells to
      disappearance of a visual pattern might be correlated to visual persistence in
      humans.

PMID- 18723082
TI  - Involvement of formyl-peptide-receptor-like-1 and phospholipase D in the
      internalization and signal transduction of amyloid beta 1-42 in glial cells.
AB  - Recent studies suggest that the formyl-peptide-receptor-like-1 (FPRL1) plays an
      essential role in the inflammatory responses of host defense mechanisms and
      neurodegenerative disorders such as Alzheimer's disease (AD). We therefore
      analyzed whether amyloid beta1-42 (Abeta1-42) increased the activity of
      phospholipase D (PLD) via FPRL1, which is an enzyme involved in the secretion,
      endocytosis and receptor signaling. PLD activity was determined using a
      transphosphatidylation assay. The internalization of Abeta1-42 via FPRL1 was
      visualized using fluorescence microscopy and quantified by ELISA (Enzyme Linked
      Immunosorbent Assay). Determining receptor activity by extracellular-signal
      regulated kinases 1/2 (ERK1/2) phosphorylation and cAMP level measurement
      verified the Abeta1-42-induced activation of FPRL1. We were able to show that
      Abeta1-42 is rapidly internalized via FPRL1 in astrocytes and microglia. PLD was
      additionally activated by Abeta1-42 and via FPRL1 in rat glial cells.
      Furthermore, the ERK1/2 phosphorylation by FPRL1 agonists was dependent on the
      PLD product phosphatidic acid (PA). Together, these data suggest that PLD plays
      an important role in the regulation of Abeta1-42-induced endocytosis and FPRL1
      receptor signaling.

PMID- 18723083
TI  - Identification and characterization of integrin-binding sialoprotein (IBSP) genes
      in reptile and amphibian.
AB  - Integrin-binding sialoprotein (IBSP) is a member of the small integrin-binding
      ligand N-linked glycoprotein (SIBLING) family; and the whole SIBLING family is
      further included in a larger secretory calcium-binding phosphoprotein (SCPP)
      family. SIBLING proteins are known to construct a part of the non-collagenous
      extracellular matrices of calcified tissues, and considered to have arisen by
      duplication and subsequent divergent evolution of a single ancient gene. To
      understand the alterations of SIBLING molecules associated with the evolution of
      calcified tissues in vertebrates, we initiated a search for lower vertebrate
      orthologs of SIBLING genes. In the present study, an IBSP ortholog from a reptile
      (caiman) and two distinct orthologs from an amphibian (African clawed toad) were
      identified and characterized. As expected, the toad IBSP genes were transcribed
      only in calcified tissue (jaw and tibia), as also seen in mammals. The caiman,
      toad, avian, and mammalian IBSPs share several unique features specific for IBSP
      and apparently have similar properties. Furthermore, analysis of the sequences
      suggested that the IBSP molecule might have gradually intensified its functions
      related to calcification during its evolutionary process through tetrapods.

PMID- 18723084
TI  - Gene expression profile of rabbit cartilage by expressed sequence tag analysis.
AB  - Although the rabbit is commonly used as an animal model for the in vivo study of
      cartilage formation or regeneration, genetic approaches to the rabbit cartilage
      are rare. We constructed an expressed sequence tag (EST) library from rabbit
      cartilage tissue for the first time to establish the foundations for genetic
      study on rabbit cartilage. From our results, we identified 2387 unique genes
      among 4885 clones, corresponding to 1839 matched to characterized genes including
      1618 genes with known function and 548 uncharacterized and novel genes. Gene
      expression profiles based on EST frequency show that type II collagen (COL2A1)
      and type X collagen (COL10A1) among collagen clones, proteoglycan 4 (PRG4) and
      decorin (DCN) among proteoglycan clones, and cartilage oligomeric matrix protein
      (COMP) and matrix Gla protein (MGP) among other extracellular matrix clones, are
      highly expressed in rabbit cartilage. In addition, gene expression analysis based
      on real-time PCR of these major extracellular matrix constituents showed that
      expression of col2a1 and col10a1 remains constant whereas the expression of prg4,
      dcn, and comp reveals substantial change with rabbit age. This EST library will
      provide a valuable resource with which to identify genes involved in the
      biochemical and physiological functions of rabbit cartilage, and will contribute
      to establishing the rabbit as an animal model for cartilage research.

PMID- 18723085
TI  - Acute airway effects of ozone-initiated d-limonene chemistry: importance of
      gaseous products.
AB  - There are concerns about ozone-initiated chemistry, because the formation of
      gaseous oxidation products and ultrafine particles may increase complaints,
      morbidity and mortality. Here we address the question whether the gaseous
      products or the ultrafine particles from the ozone-initiated chemistry of
      limonene, a common and abundant indoor pollutant, cause acute airway effects. The
      effects on the airways by d-limonene, a ca. 16s old ozone/d-limonene mixture, and
      clean air were evaluated by a mice bioassay, from which sensory irritation of the
      upper airways, airflow limitation, and pulmonary irritation can be obtained. A
      denuder was inserted to separate the ultrafine particles from the gaseous
      products prior to the exposure chamber. Reduction of mean respiratory frequency
      (>30%) and 230% increase of time of brake were observed without denuder, during
      30min exposure, to the ozonolyzed d-limonene mixture, which are indicative of
      prominent sensory effects. The initial concentrations (ppm) were 40 d-limonene
      and 4 ozone. The exposure concentrations (ppm) were about 35 d-limonene and 0.05
      ozone. Formaldehyde and residual d-limonene, the salient sensory irritants,
      accounted for up to three-fourth of the sensory irritation. The upper airway
      effects reversed to baseline upon cessation of exposure. An effect on the
      conducting airways was also significant, which did not reverse completely upon
      cessation. Airway effects were absent with the denuder inserted, which did not
      alter the size distribution of ultrafine particles ( approximately 10mg/m(3)),
      significantly. The result was statistically indistinguishable from clean dry air.
      It is concluded that ultrafine particles that are generated from ozone-initiated
      d-limonene chemistry and denuded are not causative of sensory effects in the
      airways.

PMID- 18723086
TI  - The oral bioavailability of nitrate from nitrate-rich vegetables in humans.
AB  - High dietary nitrate intake may pose a risk to human health. Since up to 80-85%
      of dietary nitrate intake comes from vegetables, the aim of this study was to
      determine the absolute bioavailability of nitrate from three nitrate-rich
      vegetables. In an open, four-way cross-over, single dose study, 12 human subjects
      underwent the following treatments: (1) intravenous infusion of 500mg sodium
      nitrate, (2) oral administration of 300g cooked spinach, (3) oral administration
      of 300g raw lettuce, and (4) oral administration of 300g cooked beetroot. The
      wash-out period between treatments was at least 6 days. Plasma samples were
      analysed to assess the nitrate and nitrite concentrations, and pharmacokinetic
      parameters were calculated. The bioavailability of nitrate was 98+/-12% from
      cooked spinach, 114+/-14% from raw lettuce and 106+/-15% from cooked beetroot.
      There was no significant increase in plasma nitrite concentrations. This study
      shows that nitrate from vegetables, whether cooked or uncooked, is absorbed very
      effectively, resulting in an absolute nitrate bioavailability of around 100%.
      Thus, reducing the amount of nitrate in vegetables can be an effective measure to
      lower the systemic nitrate exposure of the general population. However, other
      aspects, such as the costs to produce vegetables with a low nitrate content and
      the possible beneficial effects of nitrate in vegetables, need to be considered
      when evaluating the usefulness of such a measure.

PMID- 18723087
TI  - Amine-functionalized gold nanoparticles as non-cytotoxic and efficient
      intracellular siRNA delivery carriers.
AB  - Gold nanoparticles chemically modified with primary amine groups were developed
      as intracellular delivery vehicles for therapeutic small interfering RNA (siRNA).
      The positively charged gold nanoparticles could form stable polyelectrolyte
      complexes through electrostatic interactions with negatively charged siRNA
      polyethylene glycol (PEG) conjugates having a cleavable di-sulfide linkage under
      reductive cytosol condition. The resultant core/shell type polyelectrolyte
      complexes surrounded by a protective PEG shell layer had a well-dispersed
      nanostructure with a hydrodynamic diameter of 96.3+/-25.9 nm, as determined by
      dynamic light scattering and transmission electron microscopy. Confocal laser
      scanning microscopy revealed that the nanosized polyelectrolyte complexes were
      efficiently internalized in human prostate carcinoma cells, and thus enhanced
      intracellular uptake of siRNA. Furthermore, the siRNA/gold complexes
      significantly inhibited the expression of a target gene within the cells without
      showing severe cytotoxicity. The current study demonstrated that positively
      charged gold nanoparticles could be potentially applied for intracellular
      delivery of siRNA.

PMID- 18723088
TI  - Polymorphisms in the interleukin-1 (IL1) gene cluster are not associated with
      aggressive periodontitis in a large Caucasian population.
AB  - Polymorphisms in the interleukin-1 (IL1) gene have been suggested to influence
      transcription of IL1A (interleukin-1alpha) and IL1B (interleukin-1beta) and
      thereby the pathophysiology of periodontitis. This case-control association study
      on 415 northern European Caucasian patients with aggressive periodontitis (AgP)
      and 874 healthy controls was conducted to examine 10 single-nucleotide
      polymorphisms (SNPs) in the genes of the IL1 cluster for association with IL1A,
      IL1B, CKAP2L (cytoskeleton-associated protein 2-like), and IL1RN (IL-1 receptor
      antagonist). The results do not support an association between variants in the
      IL1 gene cluster and AgP. This case-control study had at least 95% power to
      detect genuine associations with variants carrying relative risks of at least 1.5
      for heterozygous carriers and 2.25 for homozygous carriers. Previous reports of
      an association between IL1 promoter SNPs and periodontitis might reflect
      subpopulation effects and have to be interpreted with care.

PMID- 18723089
TI  - "Omics" data and levels of evidence for biomarker discovery.
AB  - With the development of new technologies for assaying biological activity on a
      global basis in experimental samples, various new "-omics" signatures have been
      developed to predict disease progression. Such signatures hold the potential to
      alter the nature of clinical management of human disease. In this article, we
      describe some necessary statistical considerations needed to take these
      signatures from the discovery phase to a clinically useful assay. Much of the
      work discussed is in the area of cancer.

PMID- 18723091
TI  - Immune cells in the healing skin wound: influential players at each stage of
      repair.
AB  - Immune cells are involved in virtually every aspect of the wound repair process,
      from the initial stages where they participate in hemostasis and work to prevent
      infection to later stages where they drive scar formation. Traditional views
      maintain that a strong immune response is advantageous for wound healing, but
      newer data have questioned the validity of this idea. As a result, opinions about
      how cells of the immune system contribute to the repair process have changed
      considerably over the past few years. Here, current studies investigating how
      different immune cell lineages function in the various stages of repair will be
      reviewed and their impact on the wound healing field will be discussed.

PMID- 18723090
TI  - Ubiquitin, proteasomes and proteolytic mechanisms activated by kidney disease.
AB  - The ubiquitin-proteasome system (UPS) includes 3 enzymes that conjugate ubiquitin
      to intracellular proteins that are then recognized and degraded in the
      proteasome. The process participates in the regulation of cell metabolism. In the
      kidney, the UPS regulates the turnover of transporters and signaling proteins and
      its activity is down regulated in acidosis-induced proximal tubular cell
      hypertrophy. In chronic kidney disease (CKD), muscle wasting occurs because
      complications of CKD including acidosis, insulin resistance, inflammation, and
      increased angiotensin II levels stimulate the UPS to degrade muscle proteins.
      This response also includes caspase-3 and calpains which act to cleave muscle
      proteins to provide substrates for the UPS. For example, caspase-3 degrades
      actomyosin, leaving a 14 kDa fragment of actin in muscle. The 14 kDa actin
      fragment is increased in muscle of patient with kidney disease, burn injury and
      surgery. In addition, acidosis, insulin resistance, inflammation and angiotensin
      II stimulate glucocorticoid production. Glucocorticoids are also required for the
      muscle wasting that occurs in CKD. Thus, the UPS is involved in regulating kidney
      function and participates in highly organized responses that degrade muscle
      protein in response to loss of kidney function.

PMID- 18723092
TI  - New strategies for the isolation and activity determination of naturally
      occurring type-4 glutathione peroxidase.
AB  - Type 4 glutathione peroxidase (GPx4) is a widely expressed mammalian selenoenzyme
      known to play a vital role in cytoprotection against lipid hydroperoxide (LOOH)
      mediated oxidative stress and regulation of oxidative signaling cascades. Since
      prokaryotes are not equipped to express mammalian selenoproteins, preparation of
      recombinant GPx4 via commonly used bacterial transformation is not feasible. A
      published procedure for isolating the enzyme from rat testis employs affinity
      chromatography on bromosulfophthalein-glutathione-linked agarose as the
      penultimate step in purification. Since this resin is no longer commercially
      available and preparing it in satisfactory operational form is tedious, we have
      developed an alternative purification approach based on sequential anion
      exchange, size exclusion, and cation exchange chromatography. Final preparations
      were found to be essentially homogeneous in GPx4 (M(r) approximately 20 kDa), as
      demonstrated by SDS-PAGE with protein staining and immunoblotting. Specific
      enzymatic activity was determined using a novel thin-layer chromatographic
      approach in which the kinetics of phosphatidylcholine hydroperoxide loss or
      cholesterol-7alpha-hydroperoxide loss was monitored. A >400-fold purification of
      active enzyme has been attained. The relatively straightforward isolation
      procedure described should prove valuable for further functional studies on GPx4,
      e.g. how its ability to catalyze LOOH reduction compares with that of other LOOH
      detoxifying enzymes.

PMID- 18723093
TI  - Analysis of ESTs and expression of two peroxiredoxins in the thermally stressed
      Antarctic bivalve Laternula elliptica.
AB  - A total of 2592 expressed sequenced tags (ESTs) were generated from a cDNA
      library of the Antarctic bivalve Laternula elliptica, which is an important
      species in Antarctic coastal ecosystems. A cluster of 1789 unique sequences was
      revealed, which consisted of 273 contigs and 1076 singletons. Based on BLAST
      searches, we identified 508 genes, 56 of which were functionally related to
      immunity and stress responses, including the peroxiredoxins (Prxs). Prxs comprise
      an antioxidant protein family with conserved catalytic redox-active cysteine
      residues. We characterised two full-length cDNAs of the genes that encode
      peroxiredoxin V (lePrxV) and peroxiredoxin VI (lePrxVI) in L. elliptica. The
      lePrxV cDNA contains a 480-bp open reading frame (ORF), which encodes 159 amino
      acids, including two conserved cysteine residues that are characteristic of the
      atypical 2-Cys subgroup of the Prx family. LePrxVI contains a 702-bp ORF, which
      encodes 233 amino acids, including one conserved cysteine residue that is
      characteristic of the 1-Cys subgroup of the Prx family. RT-PCR analysis revealed
      the presence of lePrxV and lePrxVI transcripts in all the examined tissues. In
      addition, real-time PCR analysis indicated significant increases in the levels of
      lePrxV and lePrxVI transcripts were induced by thermal stress. These results
      suggest that lePrxV and lePrxVI play protective roles against oxidative stress
      caused by thermal exposure.

PMID- 18723094
TI  - Differences in early sensory-perceptual processing in synesthesia: a visual
      evoked potential study.
AB  - Synesthesia is a condition where stimulation of a single sensory modality or
      processing stream elicits an idiosyncratic, yet reliable perception in one or
      more other modalities or streams. Various models have been proposed to explain
      synesthesia, which have in common aberrant cross-activation of one cortical area
      by another. This has been observed directly in cases of linguistic-color
      synesthesia as cross-activation of the 'color area', V4, by stimulation of the
      grapheme area. The underlying neural substrates that mediate cross-activations in
      synesthesia are not well understood, however. In addition, the overall integrity
      of the visual system has never been assessed and it is not known whether wider
      differences in sensory-perceptual processing are associated with the condition.
      To assess whether fundamental differences in perceptual processing exist in
      synesthesia, we utilised high-density 128-channel electroencephalography (EEG) to
      measure sensory-perceptual processing using stimuli that differentially bias
      activation of the magnocellular and parvocellular pathways of the visual system.
      High and low spatial frequency gratings and luminance-contrast squares were
      presented to 15 synesthetes and 15 controls. We report, for the first time, early
      sensory-perceptual differences in synesthetes relative to non-synesthete controls
      in response to simple stimuli that do not elicit synesthetic color experiences.
      The differences are manifested in the early sensory components of the visual
      evoked potential (VEP) to stimuli that bias both magnocellular and parvocellular
      responses, but are opposite in direction, suggesting a differential effect on
      these two pathways. We discuss our results with reference to widespread
      connectivity differences as a broader phenotype of synesthesia.

PMID- 18723095
TI  - Evolution of a complex minisatellite DNA sequence.
AB  - Minisatellites are tandem repeats of short DNA units widely distributed in
      genomes. However, the information on their dynamics in a phylogenetic context is
      very limited. Here we have studied the organization of the MsH43 locus in several
      species of primates and from these data we have reconstructed the evolutionary
      history of this complex minisatellite. Overall, with the exception of gibbon,
      MsH43 has an organization that is asymmetric, since the distribution of repeats
      is distinct between the 5' and 3' halves, and heterogeneous since there are many
      different repeats, some of them characteristic of each species. Inspection of the
      MsH43 arrays showed the existence of many duplications and deletions, suggesting
      the implication of slippage processes in the generation of polymorphism.
      Concerning the evolutionary history of this minisatellite, we propose that the
      birth of MsH43 may be situated before the divergence of Old World Monkeys since
      we found the existence of some MsH43 repeat motifs in prosimians and New World
      Monkeys. The analysis of MsH43 in apes revealed the existence of an evolutionary
      breakpoint in the pathway that originated African great apes and humans.
      Remarkably, human MsH43 is more homologous to orang-utan than to the
      corresponding sequence in gorilla and chimpanzee. This finding does not comply
      with the evolutionary paradigm that continuous alterations occur during the
      course of genome evolution. To adjust our results to the standard phylogeny of
      primates, we propose the existence of a wandering allele that was maintained
      almost unaltered during the period that extends between orang-utan and humans.

PMID- 18723096
TI  - Phylogenetic analysis of the internal transcribed spacer (ITS) region in
      Menyanthaceae using predicted secondary structure.
AB  - Sequences of the nuclear internal transcribed spacer (ITS) regions ITS1 and ITS2
      have been used widely in molecular phylogenetic studies because of their
      relatively high variability and facility of amplification. For phylogenetic
      applications, most researchers use sequence alignments that are based on
      nucleotide similarity. However, confidence in the alignment often deteriorates at
      taxonomic levels above genus, due to increasing variability among sequences. Like
      ribosomal RNA (rRNA) and other RNA molecules, the ITS transcripts consist in part
      of conserved secondary structures ('stems' and 'loops') that can be predicted by
      mathematical algorithm. Researchers have long considered the evolutionary
      conservation of rRNA secondary structure, but until recently few phylogenetic
      analyses of the ITS regions specifically incorporated structural data. We outline
      a novel method by which to derive additional phylogenetic data from ITS secondary
      structure in order to evaluate support for relationships at higher taxonomic
      levels. To illustrate the method, we describe an example from the plant family
      Menyanthaceae. Using predicted ITS secondary structure data, we obtained a well
      resolved and moderately supported phylogeny, in which most topological
      relationships were congruent with the tree constructed using ITS nucleotide
      sequence data. Furthermore, the explicit encoding of ITS structural data in a
      phylogenetic framework allowed for the reconstruction of putative ancestral
      states and structural evolution in the functional but highly variable ITS region.

PMID- 18723097
TI  - Reduced genetic variation in the Japanese giant salamander, Andrias japonicus
      (Amphibia: Caudata).
AB  - The phylogenetic relationships among 46 samples from 27 populations of the
      Japanese giant salamander, Andriasjaponicus and its congener, A. davidianus from
      China was investigated, using 3664 bp sequences of the mitochondrial genes NADH1,
      NADH3, cyt b and CR, partial NADH6 and intervening genes. In phylogenetic trees
      constructed by MP, ML, and Bayesian methods, the family Cryptobranchidae and the
      genus Andrias both form monophyletic groups. Japanese A. japonicus and Chinese A.
      davidianus are sister taxa and can be regarded as separate species despite a
      small degree of genetic differentiation. Andriasjaponicus is divided into central
      and western clades, but the phylogenetic relationships within the latter clade
      are unresolved. As previously reported from allozyme analyses, A. japonicus
      exhibits little genetic differentiation, in strong contrast to salamanders of the
      genus Hynobius with which their distributions overlap. This reduced genetic
      variability in A. japonicus is attributable to a unique mating system of
      polygyny, delayed sexual maturity, notable longevity, life in a stable aquatic
      environment, and gigantism, as well as bottleneck effects following habitat
      fragmentation and extinction of local populations during Quaternary glaciations.
      The species is thus susceptible to extinction by potential environmental
      fluctuations, and requires extensive conservation measures.

PMID- 18723098
TI  - Influence of method of systemic administration of adenovirus on virus-mediated
      toxicity: focus on mortality, virus distribution, and drug metabolism.
AB  - INTRODUCTION: Doses of 2 x 10(12) virus particles/kilogram (vp/kg) and higher of
      recombinant human adenovirus serotype 5 (HAdV-5) given via the tail vein induce
      significant toxicity and mortality in the rat. This was not observed when doses
      of 5.7 x 10(12) vp/kg were given through a surgically implanted jugular catheter.
      Here we assess how the manner by which HAdV-5 is introduced into the systemic
      circulation affects biodistribution, transgene expression, toxicity and mortality
      0.25, 1, and 4 days after treatment in the rat. Animals were given 5.7 x 10(12)
      vp/kg of HAdV-5 expressing beta-galactosidase or saline through a jugular
      catheter or by direct tail vein injection. RESULTS: All animals survived after
      jugular vein dosing. Tail vein injection of HAdV-5 increased the mortality rate
      to 42% (p< or =0.01). All deaths occurred within 4 h. Animals dosed through the
      jugular vein had significantly higher levels of transgene expression in the liver
      and spleen and significantly more viral genomes in these tissues and kidney and
      lung within the first 24 h of viral infection compared to those dosed by tail
      vein injection (p< or =0.01). There was no significant difference between the
      groups thereafter. Samples from animals that died contained even higher levels of
      viral genomes and serum transaminases were elevated on average by a factor of 4
      at the time of death. There was no significant difference between the two dosing
      methods with respect to changes in hepatic cytochrome P450 expression and
      activity throughout the study. CONCLUSION: These findings suggest that the method
      of systemic administration should be carefully considered when assessing toxicity
      data and other parameters at early time points after virus administration in the
      rat and possibly other animal models.

PMID- 18723099
TI  - Reciprocal pathway between medullary visceral zone and hypothalamic supraoptic
      nucleus or paraventricular nucleus involved in hyperosmotic regulation.
AB  - In this study we try to simultaneously investigate the response of neurons and
      astrocytes of rats following hyperosmotic stimulation and test the possibility
      that the reciprocal pathways between medullary visceral zone (MVZ) and
      hypothalamic paraventricular nucleus (PVN) or supraoptic nucleus (SON).
      Hyperosmotic pressure animal model was established by administering 3% sodium
      chloride as drinking water to rats. The distribution and expression of the HRP
      retrogradely labeled neurons, Fos, tyrosine hydroxylase (TH) or vasopressin (VP)
      positive neuron and glial fibrillary acidic protein (GFAP) positive astrocytes in
      the MVZ, SON and PVN were observed by quadruplicate-labeling methods of WGA-HRP
      retrograde tracing combined with anti-Fos, TH (or VP) and GFAP
      immunohistochemical technique. Fos positive neurons within the MVZ, PVN and SON
      increased markedly. There were also a large number of GFAP positive structures in
      the brain and their distribution pattern was fundamentally similar or analogous
      to Fos positive neurons in the above-mentioned areas. The augmented GFAP
      reactivities took on hypertrophic cell bodies, thicker and longer processes.
      Quadruplicate immunohistochemical staining showed that a neuron could be closely
      surrounded by many astrocytes and they formed neuron-astrocytic complex (N-ASC).
      Fos+/TH+/HRP+/GFAP+ and Fos+/VP+/HRP+/GFAP+ quadruplicate labeled N-ASC could be
      found in the MVZ, PVN and SON, respectively. The present results indicated that
      the neurons and astrocytes might be very active following hyperosmotic pressure
      and N-ASC as a functional unit might serve to modulate osmotic pressure. There
      were reciprocal osmoregulation pathways between the MVZ and SON or PVN in the
      brain.

PMID- 18723100
TI  - Molecular and ultrastructural characterization of endothelial cells
      differentiated from human bone marrow mesenchymal stem cells.
AB  - In this study characterization of endothelial cells differentiated from human
      bone marrow mesenchymal stem cells (hBMCs) was investigated in relation to their
      capillary network formation potential. Differentiation was performed in presence
      of vascular endothelial growth factor (VEGF) and insulin like growth factor-1
      (IGF-1). A panel of cellular and molecular markers was used for characterization
      of the endothelial cells. The cells were strongly positive for von Willebrand
      factor (vWF) and vascular endothelial growth factor receptor 2 (VEGFR2) when
      measured at protein and mRNA levels. Development of endothelial cells was found
      to be associated with formation of typical organelles such as Weibel Palade (WP)
      bodies, Cavealae and pinocytic vesicles. Early vessel growth was also evidenced
      by showing specific junctions between the cells. The migratory and angiogenic
      properties of the cells were confirmed by showing capillary network formation in
      vitro. These results indicate that the capacity of endothelial cells
      differentiated from hBMSCs in formation of vascular system is consistent with
      molecular and structural development.

PMID- 18723101
TI  - Characterization of water of hydration fractions in rabbit skeletal muscle with
      age and time of post-mortem by centrifugal dehydration force and rehydration
      methods.
AB  - Centrifugal dehydration force (CDF) and rehydration isotherm (RHI) methods were
      used to measure and characterize hydration fractions in rabbit psoas skeletal
      muscle. The CDF method assessed fluid flow rate from rabbit muscle and hydration
      capacity of the fractions. Bulk and multiple non-bulk water fractions were
      identified. The non-bulk water was divisible into the following fractions: two
      outer non-bulk fractions, a main chain proteins backbone or double water bridge
      fraction, and a single water bridge fraction. The total non-bulk water amounts to
      about 85% of the total water in the muscle. The sizes of the water fractions (in
      g water/g dry mass) agree with a recently proposed molecular stoichiometric
      hydration model (SHM) applicable to all proteins in and out of cells (Fullerton
      GD, Cameron IL. Water compartments in cells. Methods Enzymol, 2007; Cameron IL,
      Fullerton GD. Interfacial water compartments on tendon/collagen and in cells. In:
      Pollack GH, Chin WC, editors. Phase transitions in cells. Dordrecht, The
      Netherlands: Springer, 2008). Age of the rabbit significantly slowed the flow
      rate of the outer non-bulk water fraction by about 50%. Also, muscle of the older
      rabbit (26 weeks vs. 12 weeks old) had less bulk water and less outer non-bulk
      water but the same amount of main chain backbone water compared to muscle of the
      younger rabbit. Increase in time post-mortem from 30min to 4h resulted in rigor
      mortis and a significantly slower flow rate of water from the outer non-bulk
      water fraction, which is attributed to muscle contraction, increased packing of
      contractile elements and increased obstructions to flow of fluid from the muscle
      fibers.

PMID- 18723102
TI  - Sleep is required for improving reaction times after training on a procedural
      visuo-motor task.
AB  - Sleep has been found to enhance consolidation of many different forms of memory.
      However in most procedural tasks, a sleep-independent, fast learning component
      interacts with slow, sleep-dependent improvements. Here, we show that in humans a
      visuo-motor saccade learning task shows no improvements during training, but only
      during a delayed recall testing after a period of sleep. Subjects were trained in
      a prosaccade task (saccade to a visual target). Performance was tested in the
      prosaccade and the antisaccade task (saccade to opposite direction of the target)
      before training, after a night of sleep or sleep deprivation, after a night of
      recovery sleep, and finally in a follow-up test 4 weeks later. We found no
      immediate improvement in saccadic reaction time (SRT) during training, but a
      delayed reduction in SRT, indicating a slow-learning process. This reduction
      occurred only after a period of sleep, i.e. after the first night in the sleep
      group and after recovery sleep in the sleep deprivation group. This improvement
      was stable during the 4-week follow-up. Saccadic training can thus induce covert
      changes in the saccade generation pathway. During the following sleep period,
      these changes in turn bring about overt performance improvements, presuming a
      learning effect based on synaptic tagging.

PMID- 18723104
TI  - The Stat family of transcription factors have diverse roles in mammary gland
      development.
AB  - The Stat family of transcription factors have diverse roles in mammary gland
      development. Genetic studies in mice have revealed an essential requirement for
      Stat5a in development of secretory alveolar cells during pregnancy while Stat6,
      which is normally associated with differentiation of T helper cells, is important
      in the commitment of luminal cells to this alveolar lineage. In contrast, Stat3
      is specifically activated at the initiation of post-lactational regression when
      it has an essential function in the regulation of cell death and tissue
      remodelling. Stat1 and Stat4 have been shown to be regulated during a mammary
      developmental cycle although whether they have specific, non-redundant roles is
      not clear. Thus, the adult mammary gland is somewhat unusual in that it is a
      tissue where different Stats are sequentially activated to orchestrate the
      processes of functional differentiation, cell death and tissue remodelling.

PMID- 18723103
TI  - Acute ethanol ingestion impairs appetitive olfactory learning and odor
      discrimination in the honey bee.
AB  - Invertebrates are valuable models for increasing our understanding of the effects
      of ethanol on the nervous system, but most studies on invertebrates and ethanol
      have focused on the effects of ethanol on locomotor behavior. In this work we
      investigate the influence of an acute dose of ethanol on appetitive olfactory
      learning in the honey bee (Apis mellifera), a model system for learning and
      memory. Adult worker honey bees were fed a range of doses (2.5%, 5%, 10%, or 25%)
      of ethanol and then conditioned to associate an odor with a sucrose reward using
      either a simple or differential conditioning paradigm. Consumption of ethanol
      before conditioning significantly reduced both the rate of acquisition and the
      asymptotic strength of the association. Honey bees also exhibited a dose
      dependent reduction in arousal/attention during conditioning. Consumption of
      ethanol after conditioning did not affect recall 24h later. The observed deficits
      in acquisition were not due to the affect of ethanol on gustatory sensitivity or
      motor function. However, honey bees given higher doses of ethanol had difficulty
      discriminating amongst different odors suggesting that ethanol consumption
      influences olfactory processing. Taken together, these results demonstrate that
      an acute dose of ethanol affects appetitive learning and olfactory perception in
      the honey bee.

PMID- 18723105
TI  - Seminars in cell & developmental biology.

PMID- 18723106
TI  - Effects of a high plant protein diet on the somatotropic system and
      cholecystokinin in Atlantic salmon (Salmo salar L.).
AB  - To investigate the endocrine signalling from dietary plant protein on
      somatotropic system and gastrointestinal hormone cholecystokinin (CCK), two iso
      amino acid diets based on either high plant or high fish meal protein were fed to
      Atlantic salmon. Salmon with an average starting weight of 641+/-23 g (N=180),
      were fed a fish meal (FM) based diet (containing 40% FM) or diets mainly
      consisting of blended plant proteins (PP) containing only 13% marine protein, of
      which only 5% was FM for 3 months. mRNA levels of target genes GH, GH-R, IGF-I,
      IGF-II, IGFBP-1, IGF-IR in addition to CCK-L, were studied in brain, hepatic
      tissue and fast muscle, and circulating levels of IGF-I in plasma of Atlantic
      salmon were measured. We detected reduced feed intake resulting in lower growth,
      weight gain and muscle protein accretion in salmon fed plant protein compared to
      a diet based on fish meal. There were no significant effects on the regulation of
      the target genes in brain or in hepatic tissues, but a trend of down-regulation
      of IGF-I was detected in fast muscle. Lower feed intake, and therefore lower
      intake of the indispensable amino acids, may have resulted in lower pituitary GH
      and lower IGF-I mRNA levels in muscle tissues. This, together with higher protein
      catabolism, may be the main cause of the reduced growth of salmon fed plant
      protein diet. There were no signalling effects detected either by the minor
      differences of the diets on mRNA levels of GH, GH-R, IGF-IR, IGF-II, IGFBP-1, CCK
      or plasma protein IGF-I.

PMID- 18723107
TI  - Heterologous expression of D-xylulokinase from Pichia stipitis enables high
      levels of xylitol production by engineered Escherichia coli growing on xylose.
AB  - Deletion of the Escherichia coli xylulokinase gene (xylB) is essential for
      achieving high xylitol titers from xylitol-producing E. coli strains growing on
      glucose in the presence of xylose. Our study suggests that this is due to XylB
      catalyzed toxic synthesis of xylitol-phosphate. This activity prohibits the use
      of xylose as the sole carbon source during xylitol production by E. coli. To
      overcome this limitation we turned to the yeast Pichia stipitis, which naturally
      produces xylitol, as a source of xylulokinase (Xyl3). We examined the effects of
      plasmid-based expression of Xyl3 versus XylB on growth and xylitol production by
      engineered E. coli strains. Xylulokinase activity assays show similar levels of
      functional expression of both enzymes (determined as activity on xylulose), and
      reveal significantly more activity on xylitol by XylB compared to Xyl3. (31)P NMR
      confirms the production of xylitol-phosphate from in vitro reactions with XylB.
      Lastly, the replacement of xylB with XYL3 results in drastically enhanced xylitol
      titers from E. coli strains co-expressing xylose reductase during growth on
      xylose.

PMID- 18723108
TI  - The dynamics of leukocyte infiltration in experimental autoimmune uveoretinitis.
AB  - Experimental autoimmune uveoretinitis (EAU) serves as an animal model for human
      uveitis. EAU is inducible in animals by peripheral immunization with proteins
      found in the retina that triggers an immune response which leads to tissue
      damage. This is coordinated by autoantigen specific CD4(+) T cells whose
      activation is accompanied by the infiltration of a wide range of other leukocytes
      into the retina. Infiltrating macrophages and granulocytes cause destruction by
      the release of reactive oxygen and nitrogen species but these and other
      leukocytes also regulate inflammation. This review will describe the dynamics of
      leukocyte infiltration in EAU from the initial systemic activation of T cells
      following immunization, through their traffic into the eye causing a peak of
      infiltration, and ending with a phase of secondary regulation in which, although
      clinical disease has resolved, the leukocyte composition of the eye remains
      altered.

PMID- 18723109
TI  - Use of fundus perimetry (microperimetry) to quantify macular sensitivity.
AB  - The advances in retinal imaging technologies have led to enormous innovation
      towards diagnostic in current ophthalmology, enabling the practitioner to detect
      early retinal changes and to document treatment effects. While, in the past,
      retinoscopy, visual acuity testing and perimetry played the major role in
      functional diagnostics, today, laser-based systems like laser scanning imaging
      systems especially for fluorescein-angiography, optical coherence tomography,
      electrodiagnostic systems and the analysis of retinal vessels may be used as
      well. However, the challenge to correlate subjective alterations or clinical
      changes with visual function, still remains. Micro- or fundus perimetry offers
      the option to test retinal sensitivity while directly observing the fundus. In
      this paper, we review the literature encompassing the results of more than 25
      years of fundus perimetry, i.e. perimetry under simultaneous visualization of the
      fundus. During this time, results on known diseases and reproducibility of the
      technique were published, but a lot of work was also performed on the combination
      of different examination methods, allowing a synopsis of long-term results and
      new approaches by combining different methods and improving each of them. The
      first part of this review attends to improvements of the method. The second part
      addresses the clinical and diagnostic values. The final part is dedicated to
      diagnostic and long-term observation of fundus perimetric results beginning with
      common and rare diseases like age-related macular degeneration, macular holes and
      diabetic retinopathy, various types of macular dystrophies ending with challenges
      in conventional perimetry like glaucoma and malingering. Due to the experience
      and progress in the field of fundus perimetry and retinal imaging, the method has
      long passed its role of observing and has all the potential for prediction, early
      detection and treatment-monitoring of macular diseases.

PMID- 18723110
TI  - Vitamin d.
AB  - The primary source of vitamin D is the skin, following exposure to ultraviolet
      radiation. Vitamin D is well known for its effects on stimulating calcium
      absorption and is thus essential for maintenance of normal bone. It is also
      important for muscle function and has more recently been implicated in protection
      against several diseases including diabetes. Different pathways of action have
      been described for vitamin D compounds and various analogs specific to these
      pathways have demonstrated potential for therapeutic use. Recent studies suggest
      a novel role for vitamin D compounds in protection against cancer, a proposal
      supported by substantial epidemiological evidence.

PMID- 18723111
TI  - Teneurins: important regulators of neural circuitry.
AB  - Teneurin (Ten-m/Odz) molecules represent a highly conserved family of four type
      II transmembrane proteins in vertebrates (Ten-m1-4), which exist as homodimers
      and undergo homophilic interactions. Each is expressed in distinct, and often
      interconnected, areas of the developing nervous system. Different Ten-ms have
      complementary expression patterns. In vitro and in vivo studies support roles for
      teneurins in promoting neurite outgrowth and cell adhesion. Furthermore, the
      intracellular domains of at least two teneurins can undergo proteolytic cleavage
      and translocate to the nucleus where they regulate transcriptional activity.
      Recent in vivo studies show that teneurins play important roles in regulating
      connectivity in the nervous system. Knockdown in C. elegans resulted in abnormal
      axon guidance and cell migration, while targeted deletion of Ten-m3 in mice
      revealed it is required for the guidance of retinal axons and generation of
      visual topography. It is likely that all teneurins play important roles during
      neural development.

PMID- 18723112
TI  - HIC1 (Hypermethylated in Cancer 1) epigenetic silencing in tumors.
AB  - HIC1 (Hypermethylated in Cancer 1), as it name implied, was originally isolated
      as a new candidate tumor suppressor gene located at 17p13.3 because it resides in
      a CpG island that is hypermethylated in many types of human cancers. HIC1 encodes
      a transcription factor associating an N-terminal BTB/POZ domain to five C
      terminal Kruppel-like C(2)H(2) zinc finger motifs. In this review, we will begin
      by providing an overview of the current knowledge on HIC1 function, mainly gained
      from in vitro studies, as a sequence-specific transcriptional repressor
      interacting with a still growing range of HDAC-dependent and HDAC-independent
      corepressor complexes. We will then summarize the studies that have demonstrated
      frequent hypermethylation changes or losses of heterozygosity of the HIC1 locus
      in human cancers. Next, we will review animal models which have firmly
      established HIC1 as a bona fide tumor suppressor gene epigenetically silenced and
      functionally cooperating notably with p53 within a complex HIC1-p53-SIRT1
      regulatory loop. Finally, we will discuss how this epigenetic inactivation of
      HIC1 might "addict" cancer cells to altered survival and signaling pathways or to
      lineage-specific transcription factors during the early stages of tumorigenesis.

PMID- 18723113
TI  - RBM4: a multifunctional RNA-binding protein.
AB  - RBM4, also known as Lark, was described initially as having a role in circadian
      rhythm control in Drosophila. In the last 5 years data have emerged from studies
      of mammalian cells. It is now clear that RBM4 is an RNA-binding protein involved
      in diverse cellular processes that include alternative splicing of pre-mRNA,
      translation, and RNA silencing. Its structure, similar to other RNA-binding
      proteins, contains two RNA recognition motifs and a CCHC-type zinc finger. Here
      we review current information about the function of RBM4 and its localization
      within the cell. We then speculate about its possible relationship to disease.

PMID- 18723114
TI  - SWI/SNF: a chromatin-remodelling complex with a role in carcinogenesis.
AB  - SWI/SNF is a chromatin-remodelling complex that makes DNA that has been compacted
      into nucleosomes accessible to transcription factors and repair enzymes. It does
      this by displacing DNA from the core histone surface. SWI/SNF consists of at
      least nine subunits, including one of two alternative ATPase subunits, BRM or BRG
      1, that provide the energy for remodelling. As it regulates access to DNA it
      controls many aspects of normal cellular function. Limited studies have recently
      linked loss of function of SWI/SNF subunits to cancer development, suggesting
      that it may be a tumor suppressor complex. As epigenetic repression regulates
      SWI/SNF component expression at least in some cases, restoration of function is
      therapeutically promising for cancer treatment. Considerably more research is
      required into deregulation of SWI/SNF in cancer and determination of how this
      affects tumor development. This is an exciting but poorly understood molecule
      that may have a role in carcinogenesis.

PMID- 18723115
TI  - RAP55: insights into an evolutionarily conserved protein family.
AB  - The RAP55 protein family is evolutionarily conserved in eukaryotes. Two highly
      conserved paralogues, RAP55A and RAP55B, exist in vertebrates; their functional
      properties and expression patterns remain to be compared. RAP55 proteins share
      multiple domains: the LSm14 domain, a serine/threonine rich region, an FDF
      (phenylalanine-aspartate-phenylalanine) motif, an FFD-TFG box and RGG (arginine
      glycine-glycine) repeats. Together these domains are responsible for RAP55
      proteins participating in translational repression, incorporation into mRNP
      particles, protein-protein interactions, P-body formation and stress granule
      localisation. All RAP55A proteins localise to P-body-like complexes either in the
      germline or in somatic cells. Xenopus laevis RAP55B has been shown to be part of
      translationally repressed mRNP complexes in early oocytes. Together these
      findings suggest that this protein family has evolved a common and fundamental
      role in the control of mRNA translation. Furthermore human RAP55A is an
      autoantigen detected in the serum of patients with primary biliary cirrhosis
      (PBC). The link between RAP55A, P-bodies and PBC remains to be elucidated.

PMID- 18723116
TI  - An Entamoeba cysteine peptidase specifically expressed during encystation.
AB  - Protozoan parasites of the genus Entamoeba possess a considerable number of
      cysteine peptidases (CPs), the function of most of these molecules for amoeba
      biology needs to be established. In order to determine whether CPs may play a
      role during Entamoeba stage conversion from trophozoites into cysts and vice
      versa, expression of cp genes was analysed in the reptilian parasite Entamoeba
      invadens, a model organism for studying Entamoeba cyst development. By homology
      search, 28 papain-like cp genes were identified in public E. invadens genome
      databases. For eight of these genes the expression profiles during stage
      conversion was determined. By Northern blot analysis, transcripts for eicp-a9, 
      b7, -b8 and -c2, respectively, were detected neither in trophozoites or cysts nor
      at any of the point of times analysed during stage conversion. On the other hand,
      eicp-a5 is constitutively expressed during all developmental stages, whereas eicp
      a3 and eicp-a11, respectively, are trophozoite-specific. Only eicp-b9 was found
      to be cyst-specific as it is expressed exclusively 18 to 28 h after cyst
      induction. Cyst-specific expression was confirmed by immunofluorescence
      microscopy of the corresponding protein EiCP-B9. In immature cysts, the molecule
      is located in structures that accumulate near the cyst wall, but which are
      uniformly distributed in mature cysts. The precise function of EiCP-B9 during
      Entamoeba encystation remains to be determined. However, colocalisation studies
      with an Entamoeba marker for autophagosomes suggest that EiCP-B9 is not
      associated with Entamoeba autophagy.

PMID- 18723117
TI  - Mass spectrometric analysis of lipid species of human circulating blood cells.
AB  - Circulating blood cell lipid composition may become increasingly important to
      provide new insights into cellular lipid abnormalities in diseases. Here we
      compared lipid species in monocytes, lymphocytes, granulocytes, platelets and red
      blood cells (RBC) of healthy volunteers using electrospray ionization tandem mass
      spectrometry and detected striking differences among the examined blood cells.
      The different cell types were characterized by unique lipid class and lipid
      species pattern. The predominant lipid classes were phosphatidylcholine (PC) and
      free cholesterol (FC) with cell type specific PC/FC ratios as markers of membrane
      fluidity which was 1.9 in monocytes, 1.3 in lymphocytes, 1.1 in granulocytes, 0.8
      in platelets and 0.3 in RBC, respectively. Beside a three-fold elevated ceramide
      level of 2.6 mol%, granulocytes revealed the highest percentage of
      phosphatidylethanolamine-based plasmalogens and a decreased fraction of highly
      polyunsaturated (> or =3 double bonds) species compared to other cell types.
      Furthermore RBC showed a remarkable shift of glycerophospholipid chain length and
      platelets a nearly 4-fold increase of the cholesterol ester (CE) 18:2 (linoleic
      acid) fraction (55 mol% of total CE). In conclusion, the current study is a
      detailed comparison of lipid species in circulating blood cells of healthy human
      donors. This work could be a reference for studies in different patient cohorts
      directed towards discovery of novel lipid biomarkers in circulating blood cells.

PMID- 18723118
TI  - On the prevalence of bipolar disorder in epilepsy.
AB  - Although mood disorders represent a frequent psychiatric comorbidity in epilepsy,
      data on bipolar disorder (BD) are still limited, and the role of possible
      specific confounding variables (seizures and antiepileptic drug therapy) has
      never been considered. Data for 143 adult outpatients with epilepsy assessed with
      the Mini International Neuropsychiatric Interview Plus Version 5.0.0 using the
      Epilepsy Addendum for Psychiatric Assessment, the Mood Disorder Questionnaire,
      and the Interictal Dysphoric Disorder Inventory revealed that 11.8% had the
      Diagnostic and Statistical Manual of Mental Disorders-based diagnosis of BD, only
      1.4% of whom could be considered as having "pure" BD, because in all other cases
      BD symptoms were related to phenotype copies of BD such as interictal dysphoric
      disorder of epilepsy, postictal manic or hypomanic states, and preictal
      dysphoria.

PMID- 18723119
TI  - Impact of the pediatric epilepsy scale and its responsiveness.

PMID- 18723120
TI  - Characterization of ionotropic glutamate receptors in insect neuro-muscular
      junction.
AB  - Pharmacological properties of ionotropic glutamate receptors from Calliphora
      vicina larvae neuro-muscular junction (C. vicina iGlurs) were studied by two
      electrode voltage-clamp technique. Characteristics of the ion channel pore were
      analyzed using a 26-member series of channel blockers, which includes mono- and
      dicationic derivatives of adamantane and phenylcyclohexyl. Structure-activity
      relationships were found to be markedly similar to the Ca2+-permeable AMPA
      receptors (AMPAR) but not NMDA receptors (NMDAR) channel subtype seen in
      vertebrates. Like AMPARs the channels of C. vicina iGlurs are sensitive mainly to
      dicationic compounds with 6-7 spacers between hydrophobic headgroup and terminal
      aminogroup. Study of the voltage dependence of block demonstrated that, like
      AMPARs, the C. vicina iGlur channels, are permeable to organic cations with
      dimensions exceeding 10 A. Concentration dependence of block suggests the
      presence of two distinct channel populations with approximately 20-fold different
      sensitivity to cationic blockers. The recognition domain properties are more
      complex. Besides glutamate, the channels can be activated by kainate, quisqualate
      and domoate. Competitive antagonists of AMPAR and NMDAR are virtually inactive
      against the C. vicina iGlurs as well as allosteric modulators GYKI 52466 and
      PEPA. Surprisingly, the responses were potentiated 3 times by 100 mkM of
      cyclothiazide. We conclude that the channel-forming domain of C. vicina iGlurs is
      AMPAR-like, whereas the recognition domain is specific.

PMID- 18723121
TI  - Multi-biomarker responses in the freshwater mussel Dreissena polymorpha exposed
      to polychlorobiphenyls and metals.
AB  - Contaminant related changes in behavioral, phase I and II metabolizing enzymes
      and pro-oxidant/antioxidant processes in the freshwater mussels Dreissena
      polymorpha exposed to metals and PCBs were assessed. Behavioral and biochemical
      responses including filtering rates, key phase I, II and antioxidant enzymes and
      levels of metallothioneins, glutathione, lipid peroxidation and DNA strand breaks
      were determined in digestive glands of mussels after being exposed to sublethal
      levels of mercury chloride, methyl mercury, cadmium and Aroclor 1260 during 5
      days. In 7 out of 12 responses analyzed, mussels showed significant differences
      across treatments. Unusual properties of measured ethoxyresorufin-O-deethylase
      (EROD) activities indicated that mussels lack an inducible CYP1A enzymatic
      activity. Despite of using similar exposure levels, inorganic and organic mercury
      showed different biomarker patterns of response with methyl mercury being more
      bio-available and unable to induce metallothionein proteins. Mussels exposed to
      Cd presented higher levels of metallothioneins and an enhanced metabolism of
      glutathione, whereas those exposed to Aroclor showed their antioxidant
      glutathione peroxidase related enzyme activities inhibited. Although there was
      evidence for increased lipid peroxidation under exposure to inorganic and organic
      mercury, only mussels exposed to Aroclor had significant greater levels than
      those in controls.

PMID- 18723122
TI  - Biosurveillance of emerging biothreats using scalable genotype clustering.
AB  - Developments in molecular fingerprinting of pathogens with epidemic potential
      have offered new opportunities for improving detection and monitoring of
      biothreats. However, the lack of scalable definitions for infectious disease
      clustering presents a barrier for effective use and evaluation of new data types
      for early warning systems. A novel working definition of an outbreak based on
      temporal and spatial clustering of molecular genotypes is introduced in this
      paper. It provides an unambiguous way of clustering of causative pathogens and is
      adjustable to local disease prevalence and availability of public health
      resources. The performance of this definition in prospective surveillance is
      assessed in the context of community outbreaks of food-borne salmonellosis.
      Molecular fingerprinting augmented with the scalable clustering allows the
      detection of more than 50% of the potential outbreaks before they reach the
      midpoint of the cluster duration. Clustering in time by imposing restrictions on
      intervals between collection dates results in a smaller number of outbreaks but
      does not significantly affect the timeliness of detection. Clustering in space
      and time by imposing restrictions on the spatial and temporal distance between
      cases results in a further reduction in the number of outbreaks and decreases the
      overall efficiency of prospective detection. Innovative bacterial genotyping
      technologies can enhance early warning systems for public health by aiding the
      detection of moderate and small epidemics.

PMID- 18723123
TI  - Expression of BK(Ca) channels in human pulmonary arteries: relationship with
      remodeling and hypoxic pulmonary vasoconstriction.
AB  - BACKGROUND: Potassium channels are important in pulmonary circulation because
      they have been closely related to hypoxic pulmonary vasoconstriction (HPV). The
      objective of the study was to determine whether structural changes in pulmonary
      arteries (PA), such as those observed in patients with chronic obstructive
      pulmonary disease (COPD), might be associated with changes in the mRNA expression
      of both BK(Ca) and K(V) channels and their potential relationship with HPV.
      METHODS: PA (about 1.5 mm in diameter) were obtained from 16 patients who
      underwent resective lung surgery. Intimal thickening was evaluated
      morphometrically. mRNA expression of BK(Ca), K(V)1.2, K(V)1.5, K(V)2.1 and
      K(V)3.1 was evaluated by RT-PCR in PA homogenates. Endothelial function and HPV
      were assessed in vitro in isolated PA using an organ bath. RESULTS: Intimal
      enlargement was closely associated with an increase in the expression of BK(Ca)
      channel (r=0.57, p<0.05). Pulmonary arteries incubated with charybdotoxin, a
      BK(Ca) channel blocking agent, showed lower response to endothelium-dependent
      vasodilators indicating its contribution to reduce vascular tone. Pulmonary
      arteries with more pronounced responses to hypoxia were those with greater gene
      expression of BK(Ca) channels, suggesting a potential role in attenuating HPV
      (r=0.52, p<0.05). No changes in the expression of K(V) channels were found in
      remodeled arteries. CONCLUSIONS: Structural changes of PA in COPD could alter the
      response to hypoxia due to changes in BK(Ca) potassium channel distribution.
      Since BK(Ca) channels contribute to diminish vascular tone, their increased
      expression in remodeled PA might play a role in attenuating HPV.

PMID- 18723124
TI  - A simulation based technique to estimate intracluster correlation for a binary
      variable.
AB  - Cluster randomized trials have become the design of choice for evaluating the
      effect of selected interventions on well-known health indicators such as neonatal
      mortality rate, episiotomy rate, and postpartum hemorrhage rate in a community
      setting. Determining the sample size of a cluster randomized trial requires a
      reliable estimate of cluster size and the intracluster correlation (ICC), because
      sample size can be substantially impacted by these parameters. During the design
      phase of a trial, the investigators may have estimates of the valid range of the
      health indicator which is the primary outcome variable. Furthermore,
      investigators often have an estimate of the average cluster size or range of
      cluster sizes that exist among the proposed samples they are planning to include
      in the trial. We present in this article a simulation technique to estimate the
      ICC value and its distribution for known binary outcome variables and a varying
      number of clusters and cluster sizes. We applied this technique to estimate ICC
      values and confidence intervals for a multi-country trial assessing the effect of
      neonatal resuscitation to decrease seven-day neonatal mortality, where
      communities within a country were clusters. This simulation technique can be used
      to estimate the possible ranges of the ICC values and to help to design an
      appropriately powered trial.

PMID- 18723125
TI  - Highly-restricted, cell-specific expression of the simian CMV-IE promoter in
      transgenic zebrafish with age and after heat shock.
AB  - Promoters with high levels of ubiquitous expression are of significant utility in
      the production of transgenic animals and cell lines. One such promoter is derived
      from the human cytomegalovirus immediate early (CMV-IE) gene. We sought to
      ascertain if the simian CMV-IE promoter (sCMV), used extensively in non-mammalian
      vertebrate research, also directs intense, widespread expression when stably
      introduced into zebrafish. Analysis of sCMV-driven expression revealed a temporal
      and spatial pattern not predicted by studies using the hCMV promoter in other
      transgenic animals or by observations of early F0 embryos expressing injected
      sCMV-reporter plasmids. Unexpectedly, in transgenic fish produced by both
      integration of linearized plasmid or Tol2-mediated transgenesis, sCMV promoter
      expression was generally observed in a small population of cells in telencephalon
      and spinal cord between days 2 and 7, and was thereafter confined to discrete
      regions of CNS that included the olfactory bulb, retina, cerebellum, spinal cord,
      and lateral line. In skeletal muscle, intense transgene expression was not
      observed until well into adulthood (>2-3 months post-fertilization). One final
      unexpected characteristic of the sCMV promoter in stable transgenic fish was
      tissue-specific responsiveness of the promoter to heat shock at both embryonic
      and adult stages. These data suggest that, in the context of stable transgenesis,
      the simian CMV-IE gene promoter responds differently to intracellular regulatory
      forces than other characterized CMV promoters.

PMID- 18723126
TI  - A molecular bar-coded DNA repair resource for pooled toxicogenomic screens.
AB  - DNA damage from exogenous and endogenous sources can promote mutations and cell
      death. Fortunately, cells contain DNA repair and damage signaling pathways to
      reduce the mutagenic and cytotoxic effects of DNA damage. The identification of
      specific DNA repair proteins and the coordination of DNA repair pathways after
      damage has been a central theme to the field of genetic toxicology and we have
      developed a tool for use in this area. We have produced 99 molecular bar-coded
      Escherichia coli gene-deletion mutants specific to DNA repair and damage
      signaling pathways, and each bar-coded mutant can be tracked in pooled format
      using bar-code specific microarrays. Our design adapted bar-codes developed for
      the Saccharomyces cerevisiae gene-deletion project, which allowed us to utilize
      an available microarray product for pooled gene-exposure studies. Microarray
      based screens were used for en masse identification of individual mutants
      sensitive to methyl methanesulfonate (MMS). As expected, gene-deletion mutants
      specific to direct, base excision, and recombinational DNA repair pathways were
      identified as MMS-sensitive in our pooled assay, thus validating our resource. We
      have demonstrated that molecular bar-codes designed for S. cerevisiae are
      transferable to E. coli, and that they can be used with pre-existing microarrays
      to perform competitive growth experiments. Further, when comparing microarray to
      traditional plate-based screens both overlapping and distinct results were
      obtained, which is a novel technical finding, with discrepancies between the two
      approaches explained by differences in output measurements (DNA content versus
      cell mass). The microarray-based classification of Deltatag and DeltadinG cells
      as depleted after MMS exposure, contrary to plate-based methods, led to the
      discovery that Deltatag and DeltadinG cells show a filamentation phenotype after
      MMS exposure, thus accounting for the discrepancy. A novel biological finding is
      the observation that while DeltadinG cells filament in response to MMS they
      exhibit wild-type sulA expression after exposure. This decoupling of
      filamentation from SulA levels suggests that DinG is associated with the SulA
      independent filamentation pathway.

PMID- 18723127
TI  - AlkB demethylases flip out in different ways.
AB  - Aberrant methylations in DNA are repaired by base excision repair (BER) and
      direct repair by a methyltransferase or by an oxidative demethylase of the AlkB
      type. Yang et al. [Nature 452 (2008) 961-966] have now solved the crystal
      structure of AlkB and human AlkB homolog 2 (hABH2) in complex with DNA using an
      ingenious crosslinking strategy to stabilize the DNA-protein complex. AlkB
      proteins have similar catalytic domains, but different DNA recognition motifs.
      Whereas AlkB mainly makes contact with the damaged strand, hABH2 makes numerous
      contacts with both strands. hABH2 flips out the damaged base and fills the vacant
      space by a hydrophobic amino acid residue similar to DNA glycosylases,
      essentially without distorting the double helix structure. In contrast, AlkB
      squeezes together the bases flanking the flipped-out base to maintain the base
      stack. This unprecedented flipping mechanism and the differences between AlkB and
      hABH2 in contacting the DNA strands explain their preferences for single stranded
      and double stranded DNA, respectively.

PMID- 18723128
TI  - Aberrant T cell ERK pathway signaling and chromatin structure in lupus.
AB  - Human systemic lupus erythematosus (SLE) is an autoimmune disease characterized
      by autoantibodies to nuclear components with subsequent immune complex formation
      and deposition in multiple organs. A combination of genetic and environmental
      factors is required for disease development, but how the environment interacts
      with the immune system in genetically predisposed hosts to cause lupus is
      unclear. Recent evidence suggests that environmental agents may alter T cell
      chromatin structure and gene expression through effects on DNA methylation, a
      repressive epigenetic mechanism promoting chromatin inactivation, to cause lupus
      in people with the appropriate genetic background. DNA methylation is regulated
      by ERK pathway signaling, and abnormalities in ERK pathway signaling may
      contribute to immune dysfunction in lupus through epigenetic effects on gene
      expression. This article reviews current evidence for epigenetic abnormalities,
      and in particular DNA demethylation, in the pathogenesis of idiopathic and some
      forms of drug-induced lupus, and how impaired ERK pathway signaling may
      contribute to the development of human lupus through effects on T cell DNA
      methylation.

PMID- 18723129
TI  - Altered B cell receptor signaling in human systemic lupus erythematosus.
AB  - Regulation of B cell receptor signaling is essential for the development of
      specific immunity while retaining tolerance to self. Systemic lupus erythematosus
      (SLE) is characterized by a loss of B cell tolerance and the production of anti
      self antibodies. Accompanying this break down in tolerance are alterations in B
      cell receptor signal transduction including elevated induced calcium responses
      and increased protein phosphorylation. Specific pathways that negatively regulate
      B cell signaling have been shown to be impaired in some SLE patients. These
      patients have reduced levels of the kinase Lyn in lipid raft microdomains and
      this reduction is inversely correlated with increased CD45 in lipid rafts.
      Function and expression of the inhibitory immunoglobulin receptor FcgammaRIIB is
      also reduced in Lupus IgM- CD27+ memory cells. Because the relative contribution
      of different memory and transitional B cell subsets can be abnormal in SLE
      patients, we believe studies targeted to well defined B cell subsets will be
      necessary to further our understanding of signaling abnormalities in SLE.
      Intracellular flow cytometric analysis of signaling is a useful approach to
      accomplish this goal.

PMID- 18723130
TI  - Rho GTPase-mediated pathways in mature CD4+ T cells.
AB  - Effective immune responses require the appropriate activation and differentiation
      of peripheral CD4(+) T cells. These processes need to be followed by the timely
      elimination of the responding T cells in order to restore T cell homeostasis.
      Defects in the appropriate regulation of T cell activation, expansion, and
      survival underlie the pathogenesis of many autoimmune disorders including SLE.
      The molecular machinery employed by T cells to properly control these processes
      and prevent the onset of autoimmunity has not been fully elucidated. Rho GTPases
      (which include the Rac, Cdc42, and Rho subfamilies) are molecular switches that
      control a wide range of cellular processes. Their fundamental role in biology is
      due to their ability to regulate both cytoskeletal dynamics and a large number of
      signal transduction pathways. Activation of Rho GTPases is now recognized as a
      key event in the coordination of immune responses and, particularly, in the
      activation of T cells. In this review, we will first provide an overview of the
      role of Rho GTPase-mediated pathways in mature CD4(+) T cells and then we will
      discuss recent studies, which suggest that deregulation of these pathways may
      play a role in the pathogenesis of SLE.

PMID- 18723131
TI  - Transcriptional regulation of IL-2 in health and autoimmunity.
AB  - The regulation of IL-2 production is central to our understanding of the immune
      system. Key during T cell activation, it also plays an essential role in the
      regulation of the immune response. This review discusses the function of recently
      described factors that modulate transcription and chromatin remodeling at the IL2
      promoter. Also, it addresses the role of FoxP3 as a transcriptional regulator in
      conventional T cells and regulatory T cells, and the mechanisms whereby CD28
      stabilizes IL2 transcription and translation. Finally, the alterations that
      prevent T cells from SLE patients from producing normal amounts of IL-2 upon
      stimulation are described.

PMID- 18723132
TI  - Existence of Na(+)-K(+) ATPase in sheep visceral and parietal pleura.

PMID- 18723133
TI  - Helping young independent scientists: the EMBO Young Investigator Programme
      Interview with Gerlind Wallon, Deputy Executive Director, EMBO Young Investigator
      Programme.

PMID- 18723134
TI  - Interactions between upstream and core promoter sequences determine gene
      expression and nucleosome positioning in tobacco PR-1a promoter.
AB  - The expression of PR-1a gene in tobacco is accompanied by changes in the
      chromatin architecture over its promoter region. The transcription initiates when
      the gene is induced in defense response, a condition that can be simulated
      experimentally by external application of salicylic acid. Mutagenesis of the core
      promoter sequence established that the TATA-box was critical to the expression of
      PR-1a gene. In order to study functional specificity between the core promoter
      and upstream activator region, the native core promoter was exchanged with that
      of a heterologous salicylic acid inducible promoter, Pcec. The core promoter and
      the activator region of PR-1a together determine its tightly regulated
      expression, slow kinetics of induction by SA and several fold induction of
      expression. In uninduced state, a single nucleosome was present over the core
      promoter of PR-1a. It masked both the TATA-box and the transcription initiation
      region. The transcriptional activation of the promoter by SA was accompanied by
      shift in the position of this nucleosome. The chimeric promoters failed to show
      inducibility or gave very low level of induction. They showed failure in shifting
      the nucleosome from the core promoter region. The promoter Pcec expressed
      constitutively at a high uninduced level in spite of a nucleosome over the TATA
      box region. However, in this case, the nucleosome did not mask the transcript
      initiation region. The TATA-box nucleosome was shifted as the expression
      increased further, following induction by SA. A fully induced Pcec had the TATA
      box fully exposed, though a weak nucleosome appeared on the +1 region. The
      results support a close relationship among promoter sequence architecture,
      nucleosome positioning and PR-1a expression.

PMID- 18723135
TI  - Assembly of the RFX complex on the MHCII promoter: role of RFXAP and RFXB in
      relieving autoinhibition of RFX5.
AB  - The RFX complex is key component of a multi-protein complex that regulates the
      expression of the Major Histocompatibility Class II (MHCII) genes, whose products
      are essential for the initiation and development of the adaptive immune response.
      The RFX complex is comprised of three proteins--RFX5, RFXAP, and RFXB--all of
      which are required for expression of MHCII genes. We have used electrophoretic
      mobility shift assays to characterize the DNA binding of RFX5 and the complexes
      it forms with RFXB and RFXAP, to the proximal regulatory region of the MHCII
      promoter. DNA binding of RFX5 is inhibited by domains flanking its DNA binding
      domain, and both RFXAP and RFXB are required to overcome the inhibition of both
      domains. We provide evidence that a single RFX complex binds to the proximal
      regulatory region of the MHCII promoter and identify regions of the DNA that are
      important for high affinity binding of the RFX complex. Together, our results
      provide the most detailed view to date of the assembly of the RFX complex on the
      MHCII promoter and how its DNA binding is regulated.

PMID- 18723136
TI  - Differential expression of microRNA species in organs of hibernating ground
      squirrels: a role in translational suppression during torpor.
AB  - Mammalian hibernation includes long periods of profound torpor where the rates of
      all metabolic processes are strongly suppressed in a reversible manner. We
      hypothesized that microRNAs (miRNAs), small non-coding transcripts that bind to
      mRNA, could play a role in the global suppression of mRNA translation when
      animals enter torpor. Selected miRNA species (4-9 of the following: mir-1, mir
      24, mir-15a, mir-16, mir-21, mir-122a, mir-143, mir-146 and mir-206) were
      evaluated in four organs of euthermic versus hibernating ground squirrels,
      Spermophilus tridecemlineatus using RT-PCR. Levels of mir-24 transcripts were
      significantly reduced in heart and skeletal muscle of torpid animals as were mir
      122a levels in the muscle. Mir-1 and mir-21 both increased significantly in
      kidney during torpor by 2.0- and 1.3-fold, respectively. No changes were found
      for the four miRNA species analyzed in liver. Protein levels of Dicer, an enzyme
      involved in miRNA processing were also quantified in heart, kidney and liver.
      Dicer protein levels increased by 2.7-fold in heart during hibernation but
      decreased by 60% in kidney. These data are the first report that differential
      regulation of miRNA levels occurs during mammalian hibernation and they provide a
      mechanism for reversible gene silencing during torpor that can be rapidly
      reversed to allow renewed translation of mRNA when animals arouse back to
      euthermia.

PMID- 18723137
TI  - Prediction of the fracture load of whole proximal femur specimens by topological
      analysis of the mineral distribution in DXA-scan images.
AB  - OBJECTIVE: To evaluate scanner-generated images of hip specimens obtained from
      dual energy X-ray absorptiometry (DXA) by quantitative image analysis of bone
      mineral distribution in the standard regions of interest (ROI), to predict the
      ultimate mechanical strength, and to compare the predictive potential with
      standard densitometry. MATERIALS AND METHODS: Femoral bone mineral density (BMD)
      of 100 hip specimens was obtained by DXA in the total hip, shaft, trochanteric,
      and neck ROI. Maximum compressive strength (MCS) of the specimens was measured in
      a mechanical loading device simulating a fall on the greater trochanter. The
      topology of bone mineral distribution in the scan images was evaluated by image
      processing methods based on the Minkowski functionals (MF) using the optimized
      topological parameter MF2D. Correlation and multivariate analysis were employed
      to assess the statistical potential of BMD and MF2D with respect to predict the
      mechanical strength of the femur specimens. RESULTS: R2 for the correlation
      between load-to-failure and BMD varied between 0.73 and 0.79 (exponential curve
      fit, p<0.001), being highest in the trochanteric ROI. Correlation between load-to
      failure of the specimens with the topological parameter MF2D ranged from R2 =0.8
      to 0.91 (p<0.001). In a multivariate model combining the topological information
      from all ROIs, correlation with MCS rose to R2 =0.94. CONCLUSION: The topological
      parameter MF2D can be employed to predict the mechanical strength of proximal
      femur specimens from DXA-generated images. Performance is superior to standard
      evaluation of DXA. In the future, the proposed image processing method may serve
      to improve the assessment of an individual's fracture risk.

PMID- 18723138
TI  - Comparison of three different techniques of corneal transplantation for
      keratoconus.
AB  - PURPOSE: To compare the visual outcomes following deep anterior lamellar
      keratoplasty (DALK), penetrating keratoplasty (PK), and manual top-hat PK (TH-PK)
      in subjects undergoing corneal transplantation for keratoconus (KC). DESIGN: A
      retrospective comparative case series. METHODS: settings: Cornea clinic at the
      Toronto Western Hospital. study population: Fifty patients who underwent corneal
      transplantation for KC: 17 eyes underwent DALK, 20 eyes underwent traditional PK,
      and 13 had TH-PK. main outcome measures: Preoperative and postoperative
      uncorrected and best spectacle-corrected visual acuity (UCVA, BSCVA), high-order
      aberrations (HOA), complication rate, and endothelial cell counts. RESULTS: The
      median BSCVA at 12 months follow-up was 20/40 in the DALK eyes and 20/30 in the
      traditional PK and TH-PK eyes. The mean final spherical equivalent power in the
      three groups was less than -1 diopter (D). The median astigmatism was less than
      3.5 D in the three groups. Complication rates were similar for three groups,
      although the DALK group tended toward more complications. Although DALK and TH-PK
      procedure results in significantly shorter time to suture removal (P < .01), they
      caused increased levels of HOAs (P = .02). Endothelial cell counts at 12 months
      were significantly higher in DALK and TH-PK eyes when compared to the traditional
      PK eyes (P < .001). CONCLUSIONS: DALK, PK, and TH-PK provide comparable visual
      outcomes in keratoconus patients. Although DALK and TH-PK induce more HOA, they
      speed up the time to suture removal and provide higher endothelial cell density
      at one year of follow-up.

PMID- 18723139
TI  - Combined intravitreal bevacizumab and photodynamic therapy for retinal
      angiomatous proliferation.
AB  - PURPOSE: To clarify the efficiency of combined therapy with intravitreal
      bevacizumab injections and photodynamic therapy (PDT) in patients with retinal
      angiomatous proliferation (RAP). DESIGN: Retrospective, observational,
      consecutive case series. METHODS: We retrospectively reviewed 11 consecutive eyes
      with RAP (10 patients; six men, four women) treated with intravitreal bevacizumab
      injection and PDT. Patients ranged in age from 63 to 89 years old (average, 79
      years). No patients had undergone previous treatment, and patients were followed
      for at least six months. PDT was applied one or two days after the intravitreal
      bevacizumab (1.25 mg) injection. RESULTS: The mean best-corrected visual acuity
      (BCVA) levels at baseline and one, three, and six months after treatment were
      0.16, 0.27, 0.31, and 0.29, respectively. A significant improvement in the mean
      BCVA was observed one, three, and six months after intravitreal bevacizumab
      injection and PDT (P < .01). The mean improvement in BCVA six months from
      baseline was 2.64 lines. The BCVA at six months improved in six eyes (54.5%,
      improved by three lines or more) and was stable in five eyes (45.5%). No patient
      had a decrease in the BCVA of three or more lines during any six months. The
      central retinal thickness significantly decreased from 496 +/- 189 microm to 175
      +/- 33 microm at six months (P < .001). No patients required retreatment during
      any six months. No complications such as severe vision loss, endophthalmitis, or
      systemic events developed. CONCLUSION: Combined intravitreal bevacizumab and PDT
      for RAP effectively maintained or improved VA and reduced or eliminated edema in
      the short-term.

PMID- 18723140
TI  - Long-term follow-up of punctal and proximal canalicular stenoses after silicone
      punctal plug treatment in dry eye patients.
AB  - PURPOSE: To determine the clinical value and relevance of punctal and proximal
      canalicular stenoses after punctal plug therapy in moderate to severe dry eye
      syndrome. DESIGN: Retrospective, observational case series. METHODS: Seventeen
      eyes were determined to have punctum or proximal canalicular stenoses after
      spontaneous loss of a collared silicone punctal plug. After initial diagnosis all
      patients had 12 months or more of follow-up (mean, 39; range, 12 to 87 months).
      The clinical data collected included gender and age of patients, localization of
      the stenosis, plug size, duration of punctal occlusion, subjective symptoms,
      objective ocular surface disease parameters, and occurrence of complications.
      RESULTS: A statistically significant correlation between localization of the
      stenosis and plug size, and localization of the stenosis and duration of punctal
      occlusion could not be found. At follow-up, subjective symptoms (P < .01) and
      frequency of artificial tear application (P < .001) were significantly reduced
      compared to data before plug insertion. Schirmer I test results (P < .001),
      corneal fluorescein staining (P < .01), and rose bengal staining (P < .001)
      improved significantly, whereas tear break-up time (P < .2) and impression
      cytology scores of the conjunctival surface (P = .2) remained almost unchanged.
      Complications could not be found. CONCLUSION: Within the observation period of up
      to seven years, all stenoses remained asymptomatic. Additionally, subjective
      symptoms and most dry eye parameters in our study population improved.

PMID- 18723141
TI  - Japan Ministry of Health study on prevalence of dry eye disease among Japanese
      high school students.
AB  - PURPOSE: To determine the prevalence of dry eye disease and contact lens (CL) use
      among Japanese private high school students. DESIGN: Cross-sectional prevalence
      survey. METHODS: We carried out a cross-sectional survey in 3,433 Japanese high
      school students who completed questionnaires designed to ascertain a prior
      diagnosis of dry eye disease and current symptoms of dry eye disease, as well as
      information on CL use and type of CL. We used logistic regression analysis to
      examine the associations between dry eye disease and CL use. RESULTS: Of the
      3,443 high school students, 3,433 (100%) completed the questionnaires. A total of
      2,848 boys and 585 girls joined and the age range was from 15 to 18 years.
      Clinically diagnosed dry eye disease was present in 123 boys (4.3%) and 47 girls
      (8.0%). Severe symptoms of dry eye disease were observed in 599 subjects in boys
      (21.0%) and 143 in girls (24.4%). Soft contact lens (SCL) and hard contact lens
      (HCL) use was 36.1% and 1.7%, respectively. CONCLUSION: Dry eye disease leading
      to a clinical diagnosis or severe symptoms is prevalent in the studied Japanese
      private high school students. The condition is more prevalent among female
      subjects and CL wearers. Relevant measures directed against these risks could
      provide a positive impact on public health and quality of life of high school
      students.

PMID- 18723142
TI  - Anatomic relationships between disc hemorrhage and parapapillary atrophy.
AB  - PURPOSE: Parapapillary atrophy (PPA) and disc hemorrhage (DH) are associated with
      glaucoma. We sought to determine whether they are anatomically related. DESIGN:
      Retrospective study. METHODS: All digital optic nerve stereophotographs obtained
      over a one-year period were screened for the presence of DH. Only patients with
      DH were included. The location of the greatest beta zone PPA width as defined by
      the radial distance between the scleral rim and the outer border of the beta zone
      was compared in each patient. The clock hour location of the DH was determined.
      Baseline central corneal thickness, intraocular pressure, vertical cup-to-disc
      ratio, and visual field indices were obtained. RESULTS: Photographs from 1,559
      glaucoma patients were evaluated and 46 eyes with unilateral DH were identified;
      42 (91.3%) had beta zone PPA and 38 eyes had asymmetric PPA width. DH occurred
      more frequently in the eye with the greater PPA width (29/38 eyes [76.3%]; kappa
      = 0.611; P < .001). The DH fell on the point of greatest PPA width in 10 (23.9%)
      of 42 eyes (P < .05, Fisher exact test) and within two clock hours of the
      greatest PPA width in 31 (73.8%) of 42 eyes (P < .001, Chi-square test). Logistic
      regression analysis determined that greater PPA width (odds ratio, 17.16; 95%
      confidence interval, 5.34 to 55.12; P < .001) was the only ocular characteristic
      to predict the laterality of the DH. CONCLUSIONS: DHs tend to occur in the eye
      with the greatest PPA width and usually are found within the region of its
      greatest width.

PMID- 18723143
TI  - Respective roles of acquired and congenital infections in presumed ocular
      toxoplasmosis.
AB  - PURPOSE: To analyze the roles of acquired or congenital infections in cases of
      ocular toxoplasmosis, and to compare their clinical manifestations. DESIGN:
      Retrospective, observational case series. METHODS: We analyzed the charts of
      consecutive patients with a diagnosis of ocular toxoplasmosis. Data from the
      French program for the prevention of congenital toxoplasmosis were used to assess
      the origin of infection. The data included patients' serologic status prior to
      their ocular manifestations and patients' mothers' serologic status before,
      during, and/or after pregnancy. Infections were categorized as congenital,
      acquired, or unknown. RESULTS: Of 425 cases of ocular toxoplasmosis, 100 (23.5%)
      were acquired, 62 (14.6%) were congenital, and 263 (61.9%) were of unknown
      origin. At the time of the study, the mean age of the patients with congenital
      ocular toxoplasmosis was 9.1 +/- 8.8 years, and was 21.7 +/- 12.6 years in the
      patients with acquired ocular toxoplasmosis (P < .0001). Bilateral
      chorioretinitis was observed in 4% of acquired cases and in 43.5% of congenital
      cases (P < .0001). In acquired infections, mean decimal visual acuity (VA) was
      1.0 (logarithm of the minimum angle of resolution [logMAR] 0.0 +/- 1 line) in the
      best eye and 0.4 (logMAR 0.4 +/- 5 lines) in the worst eye. In congenital cases,
      mean decimal VA was 0.8 (logMAR 0.1 +/- 4 lines) in the best eye and 0.25 (logMAR
      0.6 +/- 7 lines) in the worst eye (P < .05). CONCLUSION: In cases where the
      origin of the infection could be determined, acquired infections were a more
      frequent cause of ocular toxoplasmosis than congenital infections. Cases of
      congenital ocular toxoplasmosis were more severe than acquired cases.

PMID- 18723144
TI  - Smoking, cardiovascular risk factors, and age-related macular degeneration in
      Asians: the Singapore Malay Eye Study.
AB  - PURPOSE: To assess associations between smoking and cardiovascular risk factors
      and prevalent age-related macular degeneration (AMD) in the Singapore Malay
      population. DESIGN: Population-based, cross-sectional study. METHODS: A total of
      3,280 Malay adults age 40 to 80 years were included in the study. Early and late
      AMD signs were graded from retinal photographs following Wisconsin system. All
      participants had interview, systemic examination, and laboratory investigations
      to determine smoking status and cardiovascular risk factors. RESULTS: A total of
      3,265 participants had gradable photos, 21 (0.6%) with late AMD and 169 (5.2%)
      with early AMD. After adjusting for age and gender, current smokers were
      significantly more likely to have late AMD (odds ratio [OR], 3.79; 95% confidence
      interval [CI], 1.40 to 10.23). This association was stronger among those who
      currently smoked >5 packs of cigarettes per week (OR, 9.35; 95% CI, 2.49 to
      35.08). CONCLUSIONS: Smoking was associated with a higher late AMD prevalence in
      Malays, consistent with findings from studies in White populations.

PMID- 18723145
TI  - Effect of blinking on tear volume after instillation of midviscosity artificial
      tears.
AB  - PURPOSE: To determine by optical coherence tomography (OCT) the effect of
      blinking on ocular surface tear volume after instillation of artificial tears.
      DESIGN: Experimental study. METHODS: Normal human eyes (n = 21) were imaged to
      obtain dimensions of the tear film and menisci during blinking. The imaging was
      carried out immediately and five minutes after the instillation of 35 microl
      midviscosity artificial tears (1.0% carboxymethylcellulose; Refresh Liquigel;
      Allergan, Irvine, California, USA). The exposed ocular surface area and the lid
      lengths were used to calculate the volumes. RESULTS: Immediately after the
      instillation, total tear volume was increased (P < .001) compared with five
      minutes after the instillation, with the major increases in the lower tear
      meniscus volume and tear film volume. After the instillation, blinking caused
      tear loss in total tear volume because of the decrease of the lower tear meniscus
      volume (P < .05). In contrast, blinking increased the tear film volume (P < .05).
      At the end of the eye-opening period, tear film volume decreased and lower tear
      meniscus volume increased significantly (P < .05), with no significant changes in
      total tear volume (P > .05). During the blink cycle immediately after the
      instillation, net loss was evident in tear film volume, lower tear meniscus
      volume, and total tear volume (P < .05). CONCLUSIONS: Blinking plays a crucial
      role in distribution and removal of instilled tears. When the tear system is
      overloaded, the increase in blink output helps restore balance.

PMID- 18723147
TI  - Clinical images. Gallbladder torsion showing a "whirl sign" on a multidetector
      computed tomography scan.
AB  - An 82-year-old woman presented with a 5-day history of right upper quadrant pain.
      A physical examination showed a palpable tender mass in the right upper quadrant
      with Murphy's sign. The contrast-enhanced multidetector computed tomography
      (MDCT) scan clearly showed the twisted pedicle of the cystic duct and gallbladder
      mesentery on the right side of the gallbladder, thus showing a "whirl sign," and
      a definitive diagnosis of gallbladder torsion was made. The patient underwent a
      cholecystectomy, resulting in a favorable outcome. Therefore, the whirl sign on
      MDCT imaging can be a key to making a definitive diagnosis of gallbladder
      torsion.

PMID- 18723146
TI  - A novel mutation and phenotypes in phosphodiesterase 6 deficiency.
AB  - PURPOSE: To develop a systematic approach for the molecular diagnosis of
      retinitis pigmentosa (RP) and to report new genotype-phenotype correlations for
      phosphodiesterase 6 (PDE6)-based RP mutations. DESIGN: Clinical and molecular
      studies on a retrospective case series. METHODS: We screened 40 unrelated RP
      patients with an autosomal recessive RP microarray. Individuals with RP caused by
      PDE6 deficiency underwent genetic segregation and phenotype analysis. RESULTS: A
      disease-associated allele was identified in 32% of patients. Two probands (5%)
      had PDE6 mutations. The first proband was a compound heterozygote for known R102C
      and N216S alleles in PDE6A (MIM#180071). Pedigree analysis determined that the
      N216S variant was benign and direct sequencing discovered a novel, S303C allele.
      The second proband had a homozygous D600N mutation in the PDE6B gene
      (MIM#180072). Visual acuities of PDE6-deficient patients ranged from 20/40 to
      20/200. Clinical studies showed unusual vitreomacular traction, cystoid macular
      edema, macular atrophy, and ring hyperfluorescence in PDE6-deficient patients.
      Such extensive vitreoretinal degeneration is not characteristic of photoreceptor
      specific enzyme deficiencies. CONCLUSION: High-throughput deoxyribonucleic acid
      microarray chips can be used in combination with clinical imaging to precisely
      characterize patients with RP. Identifying the precise mutation in RP may become
      the standard of care as gene therapy emerges.

PMID- 18723148
TI  - Internal mammary sentinel node biopsy for breast cancer.
AB  - BACKGROUND: The purpose of this study was to determine the value of
      lymphoscintigraphy (LS) for internal mammary sentinel node (IMSN) identification,
      the metastatic rate, and the change in staging and treatment. METHODS: Between
      2001 and 2007 a prospective database was obtained of all patients undergoing IMSN
      biopsies using an open or thoracoscopic approach. Radiotracer injection was
      peritumoral. RESULTS: Thirty-four patients were included. There was one man.
      Three had ductal carcinoma in situ. LS showed IMSN in 47.1%. The IMSN biopsy
      success rate was 91.2%. Seven of the 28 successfully biopsied invasive cancer
      patients had metastatic IMSNs (25%). Positive IMSNs were associated with positive
      axillary nodes in 71.4% (P = .036). All patients with positive IMSNs were
      upstaged and received radiation to the internal mammary chain. In 4 of 28
      patients (14%) the chemotherapy plans were probably altered. In univariate and
      multivariate analyses tumor size, location, nuclear grade, estrogen receptors,
      progesterone receptors, Her-2, and histology were not significant predictors of
      positivity. CONCLUSIONS: IMSNs were positive in 25% of the invasive cancer
      patients. All had treatment changes. LS identified less than 50% of IMSNs. There
      are no good tumor-related predictors of IMSN positivity.

PMID- 18723149
TI  - Presidential Address: Breast surgeons as the leaders of change.

PMID- 18723150
TI  - Clinical images. Primary non-Hodgkin's lymphoma of the sigmoid colon in a child.
AB  - Primary non-Hodgkin's lymphomas of the gastrointestinal tract are rare in
      children, and few of these lymphomas are located in the sigmoid colon. The
      preoperative diagnosis rate is low. Complete resection is indicated if it can be
      done safely. Combination chemotherapy after resection is indicated.

PMID- 18723151
TI  - Factors associated with delayed postsurgical voiding interval in ambulatory
      spinal anesthesia patients: a prospective cohort study in 3 types of surgery.
AB  - BACKGROUND: Spinal anesthesia has been considered inappropriate for ambulatory
      surgery patients because of concern about voiding dysfunction. The purpose of
      this study was to analyze the relationship between voiding interval and type of
      surgery under spinal anesthesia with lidocaine and to identify other
      nonanesthetic risk factors for delayed voiding. PATIENTS AND METHODS: A
      prospective study of 406 patients undergoing to ambulatory surgery under spinal
      anesthesia with lidocaine was performed. Voiding interval was defined as the time
      in minutes from the injection of local anesthetic to the patient's first
      spontaneous voiding. Univariate and multivariate linear regression models were
      constructed to identify risk factors associated with length of voiding interval.
      RESULTS: A total of 187 patients underwent herniorrhaphy; 187 patients underwent
      lower limb surgery; and 32 patients went benign anorectal surgery. The mean +/-
      sd voiding interval was 230 +/- 50.5 minutes. Factors associated with length of
      voiding interval in the univariate analysis were sex, body mass index (BMI), type
      and duration of surgery, lidocaine dose, and volume of fluid administered.
      Factors that remained significant in the multivariate model were sex, BMI,
      lidocaine dose and type of surgery: spontaneous voiding came later after inguinal
      herniorrhaphy surgery than after lower-limb surgery (regression coefficient 20
      minutes; 95% confidence interval 11.5-29.8). Multivariate models performed for
      each type of surgery separately identified sex and lidocaine dose as factors
      related to length of voiding interval in all types of surgery. CONCLUSIONS: A
      longer voiding interval was associated with inguinal herniorrhaphy, spinal
      lidocaine dose, and male sex.

PMID- 18723152
TI  - Treatment and outcomes of patients with primary breast sarcoma.
AB  - BACKGROUND: Surgery is the main treatment for primary breast sarcoma (PBS). Here
      we characterize this disease and determine factors associated with use of
      adjuvant therapy. METHODS: Records of patients with PBS from 1986 to 2006 were
      reviewed. Overall survival (OS) was estimated by Kaplan-Meier. Relationships
      between patient variables and OS were determined using univariate Cox
      proportional hazard models. RESULTS: Thirteen patients with PBS were identified;
      10 patients underwent mastectomy, and 3 underwent partial mastectomy. Six
      patients underwent axillary staging; none were positive. Patients with tumors >5
      cm were more likely to undergo radiation therapy (P <.05). Local recurrence
      occurred in 7 patients. Metastatic disease was present in 2 patients at
      diagnosis, and 6 patients developed metastatic disease; all 8 patients died from
      their disease. Five patients remained disease free. Five-year OS was 67% (83% for
      tumors <5 cm and 42% for tumors >5 cm). Tumor size was significantly associated
      with OS (relative risk = 1.1/1 cm increase in size > 5 cm). CONCLUSIONS:
      Treatment for PBS is excision to clear margins. Axillary staging is not
      indicated. Tumor size >5 cm is the only significant prognostic indicator of
      overall survival.

PMID- 18723154
TI  - Papillary lesions of the breast diagnosed by core needle biopsy: 71 cases with
      surgical follow-up.
AB  - BACKGROUND: Papillary breast lesions comprise a spectrum of histopathologic
      diagnoses ranging from benign papillomas to papillary carcinomas. There is
      ongoing controversy regarding the management of papillary lesions diagnosed by
      core needle biopsy (CNB). Some authors advocate observation of papillary lesions
      when the CNB is benign, while others recommend surgical excision of all papillary
      lesions. The current study assessed the adequacy of CNB in evaluating papillary
      breast lesions. METHODS: A search of the pathology database at our institution
      identified 122 papillary lesions diagnosed by CNB. The study population consisted
      of 71 papillary lesions that were subsequently surgically excised. RESULTS: Of
      the 71 papillary lesions excised, 8 were malignant, 16 were atypical, and 47 were
      benign at the time of CNB. Of the 47 papillary lesions thought to be benign, 13
      (28%) revealed atypia and 4 (9%) revealed malignancy upon surgical excision. Of
      the 13 atypical papillary lesions on CNB, 7 lesions (54%) were associated with
      malignancy upon excision. Slightly over half the upgrades were due to finding
      atypia or malignancy in the tissue surrounding the papillary lesion. The total
      rate of upgrades from the CNB diagnosis to the excisional diagnosis was 38%.
      CONCLUSIONS: When a core biopsy of a papillary lesion is encountered, there is a
      strong likelihood of discovering atypia or malignancy in the index lesion or in
      close proximity. Therefore, surgical excision should be performed to avoid
      missing a malignancy and to allow for accurate breast cancer risk assessment that
      can impact survival and decisions regarding chemoprevention.

PMID- 18723153
TI  - Scientific Presentation Award: The combination of axillary ultrasound and
      ultrasound-guided biopsy is an accurate predictor of axillary stage in clinically
      node-negative breast cancer patients.
AB  - BACKGROUND: The study aim was to determine the accuracy of axillary ultrasound
      (AUS) and fine-needle aspiration biopsy (FNAB)/needle core biopsy in axillary
      breast cancer staging. METHODS: We reviewed 256 patients with clinically node
      negative breast cancer who underwent AUS +/- FNAB/needle core biopsy. AUS-guided
      FNAB/needle core biopsy was compared with histopathology to determine
      sensitivity, specificity, negative predictive value, and positive predictive
      value. RESULTS: AUS-guided FNAB/needle core biopsy and final pathology were
      positive in 72 of 256 patients (28%). In 125 of 256 cases (49%), the AUS and
      final pathology were negative. Two of 110 patients had a false-positive FNAB
      (1.8%); both received neoadjuvant chemotherapy. Nine patients (8%) had a false
      negative FNAB/needle core biopsy; the median size of lymph node metastasis was 3
      mm. The sensitivity and specificity of AUS-guided FNAB/needle core biopsy was 71%
      and 99%, respectively, with a negative predictive value of 84% and a positive
      predictive value of 97%. CONCLUSIONS: AUS-guided FNAB/needle core biopsy is
      accurate in predicting the status of the axilla in 70% of clinically node
      negative breast cancer patients. This technique is minimally invasive with a low
      complication rate and can obviate the need for staged lymph node procedures.

PMID- 18723155
TI  - Scientific Impact Recognition Award: Molecular breast imaging: a review of the
      Mayo Clinic experience.
AB  - BACKGROUND: Molecular breast imaging (MBI) depicts functional uptake of targeted
      radiotracers in the breast using dedicated gamma cameras. METHODS: MBI studies
      were performed under several institutional protocols evaluating the use of MBI in
      screening and diagnosis. RESULTS: By using a single-head system, sensitivity for
      breast cancer detection was 85% (57 of 67) overall and 29% for tumors 5 mm or
      less in diameter. Sensitivity improved to 91% (117 of 128) overall and 69% for
      tumors 5 mm or less using a dual-head system. In 650 high-risk patients
      undergoing breast cancer screening, MBI detected 7 cancers, 5 of which were
      missed on mammography. In 24 of 149 (16%) breast cancer patients MBI detected
      additional disease not seen on mammography. The sensitivity of MBI was 88% (83 of
      94) for invasive ductal carcinoma, 79% (23 of 29) for invasive lobular carcinoma,
      and 89% (25 of 28) for ductal carcinoma in situ. CONCLUSIONS: MBI can detect
      invasive ductal carcinoma, ductal carcinoma in situ, and invasive lobular
      carcinoma. It has a promising role in evaluating the extent of disease and
      multifocal disease in the breast for surgical treatment planning.

PMID- 18723156
TI  - Editorial comment: What surgeons tell their patients about the intra-operative
      role of residents: a qualitative study.

PMID- 18723158
TI  - Clinical images. Atypical midcycle pain.
AB  - A 16-year-old female presented with acute-onset abdominal pain and an initial
      diagnosis of midcycle pain. Subsequent pelvic ultrasound and diagnostic
      laparoscopy showed a large mass in the pouch of Douglas. The patient underwent a
      laparotomy and excision of a mass from a loop of jejunum. This case highlights
      the difficulties in diagnostic differentiation relating to large pelvic masses in
      young females.

PMID- 18723157
TI  - Intraoperative cerebral high-intensity transient signals and postoperative
      cognitive function: a systematic review.
AB  - BACKGROUND: Much attention in the literature has focused on the relationship
      between perioperative microemboli during cardiac and vascular surgery and
      postoperative cognitive decline. Transcranial Doppler ultrasonography (TCD) has
      been used to measure high-intensity transient signals (HITS), which represent
      microemboli during cardiac, vascular, and orthopedic surgery. The purpose of this
      study was to systematically examine the literature with respect to HITS and
      postoperative cognitive function. METHODS: Systematic PubMed searches identified
      articles related to the use of TCD and cognitive function in the surgical
      setting. RESULTS: The literature remains largely undecided on the role of HITS
      and cognitive impairment after surgery, with most studies being underpowered to
      show a relationship. Although the cognitive effects of HITS may be difficult to
      detect, subclinical microemboli present potential harm, which may be modifiable.
      CONCLUSIONS: TCD represents a tool for intraoperative cerebral monitoring to
      reduce the number of HITS during surgery.

PMID- 18723159
TI  - The use of a gamma probe and radioactive technetium to identify obscure
      gastrointestinal bleeding.
AB  - Lower gastrointestinal bleeding is a common cause of hospital admission. This
      bleeding is most often secondary to diverticuli, malignancy, or colitis. Rarely,
      the location of lower gastrointestinal bleeding cannot be identified after
      exhaustive efforts with endoscopy, angiography, and other modalities. To address
      this unique clinical situation, we present a modification of the technique for
      sentinel lymph node biopsy in which a gamma probe is used to identify the source
      of hemorrhage. This is completed intraoperatively after preoperative radioactive
      technetium sulfur colloid is injected at the time of angiography. This approach
      involves minimal risk and provides the surgeon with an improved ability to
      localize bleeding, as well as potentially minimize the extent of bowel resection.

PMID- 18723160
TI  - Prototype awareness enhancing and monitoring device for trichotillomania.
AB  - Trichotillomania is an impairing condition that involves repetitive hair pulling.
      Habit reversal therapy is helpful for many persons with this disorder.
      Unfortunately, habit reversal therapy is not helpful for everyone and maintenance
      of gains is often problematic. Successful habit reversal therapy requires the
      individual to be aware of hair pulling and handling. Unfortunately, most people
      with trichotillomania report that much of their plucking occurs outside of
      awareness. Monitoring of trichotillomania behaviors is also problematic. The
      present project involved a pilot study of a prototype awareness enhancing and
      monitoring device aimed at increasing the effectiveness of habit reversal
      therapy. The device included a watch, bracelet, magnetic necklace, and a pager
      that was hard-wired for remote activation of a vibrating alert when hair pulling
      behaviors occurred. Following structured diagnostic assessment, three female
      participants were randomly assigned to be initially observed for varied lengths
      of time without the device followed by observation with the device in place. The
      results indicated a marked reduction in trichotillomania behaviors when the
      device was in place. Semi-structured interviews revealed that the device was very
      effective in enhancing awareness and monitoring of trichotillomania related
      behaviors and enthusiastic acceptance of the device was provided by all
      participants.

PMID- 18723161
TI  - Anticipation of interoceptive threat in highly anxiety sensitive persons.
AB  - Anticipatory anxiety plays a major role in the etiology of panic disorder.
      Although anticipatory anxiety elicited by expectation of interoceptive cues is
      specifically relevant for panic patients, it has rarely been studied. Using a
      population analogue in high fear of such interoceptive arousal sensations (highly
      anxiety sensitive persons) we evaluated a new experimental paradigm to assess
      anticipatory anxiety during anticipation of interoceptive (somatic sensations
      evoked by hyperventilation) and exteroceptive (electric shock) threat. Symptom
      reports, autonomic arousal, and defensive response mobilization (startle eyeblink
      response) were monitored during threat and matched safe conditions in 26 highly
      anxiety sensitive persons and 22 controls. The anticipation of exteroceptive
      threat led to a defensive and autonomic mobilization as indexed by a potentiation
      of the startle response and an increase in skin conductance level in both
      experimental groups. During interoceptive threat, however, only highly anxiety
      sensitive persons but not the controls exhibited a startle response potentiation
      as well as autonomic activation. The anticipation of a hyperventilation procedure
      thus seems a valid paradigm to investigate anticipatory anxiety elicited by
      interoceptive cues in the clinical context.

PMID- 18723162
TI  - Combining early markers strongly predicts conversion from mild cognitive
      impairment to Alzheimer's disease.
AB  - BACKGROUND: The utility of combining early markers to predict conversion from
      mild cognitive impairment (MCI) to Alzheimer's Disease (AD) remains uncertain.
      METHODS: Included in the study were 148 outpatients with MCI, broadly defined,
      followed at 6-month intervals. Hypothesized baseline predictors for follow-up
      conversion to AD (entire sample: 39/148 converters) were cognitive test
      performance, informant report of functional impairment, apolipoprotein E
      genotype, olfactory identification deficit, and magnetic resonance imaging (MRI)
      hippocampal and entorhinal cortex volumes. RESULTS: In the 3-year follow-up
      patient sample (33/126 converters), five of eight hypothesized predictors were
      selected by backward and stepwise logistic regression: Pfeffer Functional
      Activities Questionnaire (FAQ; informant report of functioning), University of
      Pennsylvania Smell Identification Test (UPSIT; olfactory identification),
      Selective Reminding Test (SRT) immediate recall (verbal memory), MRI hippocampal
      volume, and MRI entorhinal cortex volume. For 10% false positives (90%
      specificity), this five-predictor combination showed 85.2% sensitivity, combining
      age and Mini-Mental State Examination (MMSE) showed 39.4% sensitivity; combining
      age, MMSE, and the three clinical predictors (SRT immediate recall, FAQ, and
      UPSIT) showed 81.3% sensitivity. Area under ROC curve was greater for the five
      predictor combination (.948) than age plus MMSE (.821; p = .0009) and remained
      high in subsamples with MMSE > or = 27/30 and amnestic MCI. CONCLUSIONS: The five
      predictor combination strongly predicted conversion to AD and was markedly
      superior to combining age and MMSE. Combining the clinically administered
      measures also led to strong predictive accuracy. If independently replicated, the
      findings have potential utility for early detection of AD.

PMID- 18723163
TI  - Task complexity enhances response inhibition deficits in childhood and adolescent
      attention-deficit/hyperactivity disorder: a meta-regression analysis.
AB  - BACKGROUND: The ability to inhibit motor responses, as assessed by the stop
      signal reaction time (SSRT), is impaired in children and adolescents with
      attention-deficit/hyperactivity disorder (ADHD). However, the between-study
      variation in effect sizes is large. The aim of this study was to investigate
      whether this variability can be explained by between-study variation in Go task
      complexity. METHOD: Forty-one studies comparing children or adolescents diagnosed
      with ADHD to normal control subjects were incorporated in a random-effects meta
      regression analysis. The independent variables were a global index of Go task
      complexity (i.e., mean reaction time in control subjects [RTc]) and a more
      specific index (i.e., spatial compatibility of the stimulus-response mapping).
      The dependent variable was the SSRT difference between ADHD and control subjects.
      RESULTS: The SSRT difference increased significantly with increasing RTc.
      Moreover, the SSRT difference was significantly increased in studies that
      employed a noncompatible, that is, arbitrary, mapping compared with studies that
      incorporated a spatially compatible stimulus-response mapping. CONCLUSIONS: These
      results indicate that inhibitory dysfunction in children and adolescents with
      ADHD varies with task complexity: inhibitory dysfunction in ADHD is most
      pronounced for spatially noncompatible responses. Explanations in terms of
      inhibition and working memory deficits and a tentative neurobiological
      explanation are briefly discussed.

PMID- 18723165
TI  - Efficient regioselective chemical modifications of maltotriose: an easy access to
      oligosaccharidic scaffold.
AB  - Regioselective chlorination of fully unprotected maltotriose has given in high
      yield 1(I),2(I-III),3(I-III),4(III)-octa-O-acetyl-6(I-III)-trichloro-6(I-III)
      trideoxymaltotriose. Moreover, regioselective ditritylation of methyl beta
      maltotrioside has provided the two regioselectively C(6)-disubstituted
      trisaccharides. Selective deprotection of these new compounds gives the
      corresponding diol and halogenated analogues, respectively, in good yield. All
      compounds have been completely characterized and the substitution pattern in the
      oligosaccharidic sequence has been elucidated. A new family of amphiphilic
      carbohydrates, namely the 6-deoxy-6-alkylthiomaltotriose derivatives, bearing
      either two or three thioalkyl hydrophobic chains, respectively, has been
      synthesized. Critical micellar concentration (CMC) values as well as the
      antimicrobial properties have been evaluated for amphiphilic compounds.

PMID- 18723164
TI  - Early life stress alters behavior, immunity, and microbiota in rats: implications
      for irritable bowel syndrome and psychiatric illnesses.
AB  - BACKGROUND: Adverse early life events are associated with a maladaptive stress
      response system and might increase the vulnerability to disease in later life.
      Several disorders have been associated with early life stress, ranging from
      depression to irritable bowel syndrome. This makes the identification of the
      neurobiological substrates that are affected by adverse experiences in early life
      invaluable. METHODS: The purpose of this study was to assess the effect of early
      life stress on the brain-gut axis. Male rat pups were stressed by separating them
      from their mothers for 3 hours daily between postnatal days 2-12. The control
      group was left undisturbed with their mothers. Behavior, immune response, stress
      sensitivity, visceral sensation, and fecal microbiota were analyzed. RESULTS: The
      early life stress increased the number of fecal boli in response to a novel
      stress. Plasma corticosterone was increased in the maternally separated animals.
      An increase in the systemic immune response was noted in the stressed animals
      after an in vitro lipopolysaccharide challenge. Increased visceral sensation was
      seen in the stressed group. There was an alteration of the fecal microbiota when
      compared with the control group. CONCLUSIONS: These results show that this form
      of early life stress results in an altered brain-gut axis and is therefore an
      important model for investigating potential mechanistic insights into stress
      related disorders including depression and IBS.

PMID- 18723166
TI  - Synthesis of iminoalditol and N-alkyl iminoalditol derivatives of
      ribopyranosides.
AB  - Iminoalditol analogs of ribopyranosides were prepared by reduction of a
      vinylogous urethane intermediate formed from methyl 2-C-(5-O-methanesulfonyl-beta
      d-ribofuranosyl)acetate (1) by treatment with sodium azide in DMF at reflux. The
      N-alkylated analogs were synthesized either by N-alkylation of the corresponding
      parent iminoaldithol or, more efficiently, from the product of the reaction of 1
      with various alkylamines. The latter process involves an S(N)2 substitution at C
      5 by the amine followed by an intramolecular hetero-Michael reaction under basic
      conditions. The 'aglycon' of the iminoalditol was also modified through amidation
      and esterification.

PMID- 18723167
TI  - The conjunction fallacy and the many meanings of and.
AB  - According to the conjunction rule, the probability of A and B cannot exceed the
      probability of either single event. This rule reads and in terms of the logical
      operator wedge, interpreting A and B as an intersection of two events. As
      linguists have long argued, in natural language "and" can convey a wide range of
      relationships between conjuncts such as temporal order ("I went to the store and
      bought some whisky"), causal relationships ("Smile and the world smiles with
      you"), and can indicate a collection of sets rather than their intersection (as
      in "He invited friends and colleagues to the party"). When "and" is used in word
      problems researching the conjunction fallacy, the conjunction rule, which assumes
      the logical operator wedge, therefore cannot be mechanically invoked as a norm.
      Across several studies, we used different methods of probing people's
      understanding of and-conjunctions, and found evidence that many of those
      respondents who violated the conjunction rule in their probability or frequency
      judgments inferred a meaning of and that differs from the logical operator wedge.
      We argue that these findings have implications for whether judgments involving
      ambiguous and-conjunctions that violate the conjunction rule should be considered
      manifestations of fallacious reasoning or of reasonable pragmatic and semantic
      inferences.

PMID- 18723169
TI  - Versatility of the island forearm flap in the management of extensive skin
      defects of the hand.
AB  - SUMMARY: Even the most meticulously performed reconstructions of the hand are at
      risk of failure if appropriate soft tissue coverage has not been ensured. The
      radial forearm flap has been found useful in various applications involving soft
      tissue coverage of skin defects not only of the upper and lower extremities, but
      in other plastic reconstructive procedures as well. Most hand and microsurgeons
      will agree that the island radial forearm flap offers several important
      advantages for covering defects in the hand. The versatility of this flap offers
      valuable options for the surgeon as it may include bone, nerve or tendons to be
      used as a complex flap. Its reliability is attributed to the fact that since no
      anastomosis of vessels is required, the risk of thrombus formation at the
      anastomosis site is eliminated.

PMID- 18723170
TI  - Nerve repair: experimental and clinical evaluation of neurotrophic factors in
      peripheral nerve regeneration.
AB  - SUMMARY: Neurotrophic factors are a family of polypeptides required for survival
      of discrete neuronal populations. In the normal state such factors are mostly
      synthesised by target tissues and are used for the viability of the nerve-cell
      bodies. After nerve injury, neurotrophic factors (NFs) are synthesised by non
      neuronal (Schwann cells and fibroblasts) in the nerve trunk, and act to support
      the outgrowth of axons. NFs can be classified into three major groups: (1)
      neurotrophins; (2) neurokines; and (3) the transforming growth factor beta (TGF)
      beta superfamily.

PMID- 18723168
TI  - Quantified activity pattern data from 6 to 27-month-old farmworker children for
      use in exposure assessment.
AB  - This study was conducted to describe exposure prone behaviors of infants and
      toddlers in the farmworker community. Analysis of hand and mouth contact
      frequencies and durations aids understanding of how children interact with their
      environment and are exposed via contact with surfaces. All 23 participating
      children (8 female infants, 5 male infants, 5 female toddlers and 5 male
      toddlers) lived with at least one farmworker. Children were videotaped at home
      for 2-6 h. Video footage was translated into micro-level activity time series
      (MLATS) for both hands and the mouth. MLATS were processed to calculate hourly
      duration in microenvironments, contact frequency, hourly contact duration and
      median contact duration. The median hourly duration spent indoors was 53 min/h.
      The median hand-to-mouth frequency was 15.2 events/h and the median object-to
      mouth frequency was 27.2 events/h. The hourly mouthing duration was 1.2 and 2.2
      min/h with the hands and objects, respectively. The median mouthing duration with
      hands and objects was 2 s. The median contact frequency for both hands combined
      was 689.4 events/h with an hourly contact duration of 100.5 min/h and a median
      contact duration of 3s. Infants had higher mouthing frequencies with non-dietary
      objects while toddlers had higher mouthing frequencies with objects associated
      with pica (i.e., paper). Boys had higher contact frequencies while girls had
      longer contact durations. These sub-group differences indicate factors such as
      age and gender should be accounted for when conducting exposure assessments.
      Contact frequencies in this study are higher than current US EPA recommendations,
      questioning their protective value for infants and toddlers.

PMID- 18723171
TI  - Industrial contaminants in Antarctic biota.
AB  - A critical review of the levels and patterns of industrial contaminants in biota
      from Antarctica and the Southern Ocean revealed that concentrations are low with
      respect to other regions of the world, although in some specimens/species (e.g.
      leopard seal, some invertebrates) they are occasionally high and comparable to
      those found in regions with a strong human impact; the highest levels of
      persistent organic pollutants (POPs) were detected in the vicinity of scientific
      stations. Bioconcentration prevails at the lower trophic levels of pelagic food
      webs, while biomagnification can become the main route of contamination at higher
      levels. In a benthic food web, biomagnification poses a major risk for organisms
      that accumulate lipids to overwinter, compared to those that accumulate glycogen.
      Hexachlorobenzene, DDTs and chlordanes showed similar concentrations and patterns
      in the 1980s-1990s period in organisms from Western and Eastern Antarctica, while
      the polychlorinated biphenyls time trend was different in a variety of species
      from the two regions.

PMID- 18723172
TI  - H(2) and CO(2) coadsorption effects in CO adsorption over nanosized Au/gamma
      Al(2)O(3) catalysts.
AB  - The present study is focused on the kinetic investigation of the effects of H(2)
      and CO(2) on the rates related to the elementary steps of CO sorption over
      Au/gamma-Al(2)O(3). The kinetic study was carried out in a wide temperature range
      (50-300 degrees C) by the novel methodology of reversed flow gas chromatography
      (RF-GC). The findings of preliminary coadsorption studies of CO with H(2), O(2)
      and O(2)+H(2) indicate that a reductive pre-treatment of the Au catalyst with a
      mixture of CO in excess of H(2) can be more beneficial concerning CO oxidation
      activity at low temperatures, compared to the usual reduction in a diluted
      hydrogen atmosphere, most probably due to the easier activation of oxygen
      molecules. At high temperatures the rate of reversed water gas shift reaction
      becomes significant resulting in H(2) and CO(2) consumption. The kinetic findings
      indicate that hydrogen strongly influences the adsorption of CO over Au/gamma
      Al(2)O(3), by enhancing CO adsorption at lower temperatures and weakening the
      strength CO binding. On the other hand, CO(2) adsorption competes that of CO
      under hydrogen-rich conditions. However, the strength of CO(2) bonding is higher
      compared to that of CO and it further increases at higher temperatures, in
      agreement with the observed deactivation of the selective CO oxidation in the
      presence of CO(2).

PMID- 18723173
TI  - Label-free detection of amino acids using gold nanoparticles in electrokinetic
      chromatography-thermal lens microscopy.
AB  - To achieve label-free detection of amino acids in capillary-based electrokinetic
      chromatography-thermal lens microscopy (EKC-TLM), gold nanoparticles (GNPs),
      which possess the absorption around 500nm attributed to surface plasmon resonance
      (SPR), were added to the background solution (BGS). Since the SPR absorption of
      the GNPs exhibits a sensitive response toward environmental changes and the
      degree of aggregation, the sensitive detection of non-absorbing species is
      expected by using the GNPs in EKC-TLM (GNP-EKC-TLM). In the GNP-EKC-TLM analysis
      of glutamic acid (Glu), a sharp peak was observed when the GNPs were added to the
      BGS. The plot of the peak area of Glu against its concentration gave a good
      linear relationship and the limit of detection was estimated to be 25mug/mL.
      Furthermore, a baseline separation of lysine and Glu was successfully achieved.
      Thus, the EKC separation and label-free TLM detection of the amino acids can be
      realized only by adding the GNPs into the BGSs.

PMID- 18723174
TI  - Importance of extracting solvent vapor pressure in headspace liquid-phase
      microextraction.
AB  - Of the many parameters that affect the enrichment factors in headspace liquid
      phase microextraction, in this study, we systematically investigated the
      influence of the vapor pressure of the extracting solvent. Seven extracting
      solvents with different vapor pressures were selected and tested. It was found
      that the vapor pressure of the extracting solvent dramatically affects the
      enrichment factor and the factor was increasing by decreasing the extracting
      solvent vapor pressure under given experimental conditions. The result was
      validated for volatile organic compounds such as polynuclear aromatic
      hydrocarbons, organochlorine pesticides and polychlorinated biphenyls.

PMID- 18723175
TI  - Application and exploration of fast gas chromatography-surface acoustic wave
      sensor to the analysis of thymus species.
AB  - Fast gas chromatography combined with surface acoustic wave sensor (GC/SAW) has
      been applied for the detection of volatile aroma compounds emanated from thymus
      medicinal plants such as T. quinquecostotus (Jeju and Mt. Gaya in South Korea),
      T. quinquecostotus var. japonica (Ulreung island in South Korea), T. mongolicus
      (Northeastern Asia), and T. serpyllum (Europe). The GC/SAW involving the
      fragrance pattern analysis provides a novel analytical method with a very fast
      separation and characterization of aromas caused by the delicate difference of
      chemical composition according to botanical and geographical origin. On the
      comparison of experiments, the characteristic components and analytical tendency
      for air-dried thymus species detected by GC/SAW appear to be quite similar to
      those obtained by headspace solid-phase microextraction (HS-SPME)-GC-MS, but the
      abundance ratios between these two methods are different. In addition to that,
      the discrimination of various thymus species by using VaporPrint image based on
      GC/SAW provides a quite reliable result. On the basis of principal component
      analysis (PCA) results, the ability for classification among species of
      completely different chemotypes by HS-SPME-GC-MS is good enough, but the
      classification of same chemotypes species which are from different geographical
      origin in same country, original species and its variety, an air-drying term for
      13 days and 16 months appear much lower than GC/SAW. Interestingly, the present
      experiment reveals that the air-drying term influences the aroma composition: the
      concentration of the pharmacologically active species, monoterpene phenol
      (thymol), reaches its highest concentrations after it was dried for 5 days or 13
      days, which is much higher than in fresh or over-dried for a long times.

PMID- 18723176
TI  - Preparation of an open-tubular capillary column with a monolithic layer of S
      ketoprofen imprinted and 4-styrenesulfonic acid incorporated polymer and its
      enhanced chiral separation performance in capillary electrochromatography.
AB  - Enhanced chiral separation performance has been observed for ketoprofen
      enantiomers in capillary electrochromatography (CEC) with an open-tubular (OT)
      column prepared with a specific molecule imprinted polymer (MIP) on the innerwall
      of 50mum ID capillary. The column was prepared by in situ thermal polymerization
      inside the pretreated and silanized fused silica capillary. A specific diluted
      monomer mixture composed of S-ketoprofen, methacrylic acid (MAA, functional
      monomer), ethylene glycol dimethacrylate (EDMA, cross-linker), and 4
      styrenesulfonic acid (4-SSA) dissolved in 9/1 (v/v) acetonitrile/2-propanol was
      used to fabricate the OT-MIP layer. 4-SSA was added to form a MIP layer capable
      of stable and strong electro-osmotic flow (EOF) over the pH range of this study
      securing CEC elution of ketoprofen having partial negative charge near the
      optimized pH. Various parameters such as buffer pH, organic modifier composition,
      salt concentration, and applied potential have been optimized for CEC chiral
      separation of ketoprofen enantiomers. Very good separation selectivity and
      efficiency were observed, thus the chromatographic resolution of ketoprofen
      enantiomers was as high as 10.5, and the number of theoretical plates of R
      ketoprofen, 156,000/m (40,000/m for S-ketoprofen), which proves that the OT-MIP
      CEC type approach is a promising strategy in MIP study.

PMID- 18723177
TI  - Multiresidue determination of sulfonamides in chicken meat by polymer monolith
      microextraction and capillary zone electrophoresis with field-amplified sample
      stacking.
AB  - A method based on poly(methacrylic acid-co-ethylene glycol dimethacrylate) (MAA
      EGDMA) monolith microextraction (PMME) and online preconcentration technique of
      field-amplified sample stacking (FASS) was proposed for sensitive capillary
      electrophoresis-ultraviolet (CE-UV) analysis of 12 sulfonamides (sulfamethazine,
      sulfamethoxypyridazine, sulfathiazole, sulfamerazine, sulfameter, sulfadoxine,
      sulfadimethoxine, sulfamonomethoxine sodium, sulfachlorpyridazine,
      sulfamethoxazole, sulfamethizole, and sulfisoxazole) in chicken samples. The
      conditions of PMME were optimized for the improvement of extraction efficiency
      and reduction of the matrix interferences from chicken sample. The best
      separation was achieved within 15 min using a buffer of 100 mM phosphate
      electrolyte (pH 7.3) with temperature and voltage of 20 degrees C and 25 kV,
      respectively. By applying FASS, detection limits of 3.49-16.7 ng/g were achieved
      with satisfactory precision (RSD<or==13%) and recovery (96.3-104%) over a linear
      range of 50-1,000 ng/g for most analytes.

PMID- 18723178
TI  - Enantiomeric reversed-phase high-performance liquid chromatography resolution of
      D-/L-penicillamine after spirocyclization with ninhydrin and by using copper(II)
      L-proline complex as a chiral selector in the mobile phase.
AB  - A new HPLC method by fluorescence or UV/vis absorbance detection has been
      developed for the separation and quantification of penicillamine stereoisomers
      after their spirocyclization with ninhydrin. The separation was performed on an
      achiral C18 column by isocratic elution with a copper(II)-l-proline complex as a
      chiral selector in the mobile phase. The method was able to detect traces of l
      penicillamine in samples of d-penicillamine below 0.1% in fairly short times
      (about 16 min) with a good resolution (R(s)=1.31). On the whole, the method was
      found to be stable and useful in the quality control of the bulk material and
      formulations.

PMID- 18723179
TI  - Preparative isolation and purification of two benzoxazinoid glucosides from
      Acanthus ilicifolius L. by high-speed counter-current chromatography.
AB  - The first preparative separation of two benzoxazinoids, (2R)-2-O-beta-d
      glucopyranosyl-2H-1,4-benzoxazin-3(4H)-one (HBOA-Glc) and (2R)-2-O-beta-d
      glucopyranosyl-4-hydroxy-2H-1,4-benzoxazin-3(4H)-one (DIBOA-Glc), by means of
      high-speed counter-current chromatography (HSCCC) from the n-butanol extract of
      Acanthus ilicifolius L. is presented. The two-phase solvent system containing
      ethyl acetate-n-butanol-0.5%NH(4)OH (2:3:5, v/v/v, system B) was selected for the
      one-step HSCCC separation of HBOA-Glc and DIBOA-Glc according to the partition
      coefficient values (K) for target compounds and the separation factor (alpha)
      between the two target compounds. In the one-step HSCCC separation using solvent
      B, from 100mg n-butanol extract of A. ilicifolius, 6.3 mg HBOA-Glc and 6.8 mg
      DIBOA-Glc were isolated with purities of 90.3% and 80.2%, respectively. In order
      to obtain the two target compounds with higher purity, a second separation
      process was developed comprising two steps. In the two-step separation, the
      sample was first pre-purified by HSCCC using ethyl acetate-n-butanol-water
      (2:3:5, v/v/v, system A) solvent system and then purified using solvent system B.
      A 100-mg amount of the n-butanol extracts of A. ilicifolius was separated to
      yield 5.8 mg of HBOA-Glc and 4.8 mg of DIBOA-Glc with purities of 97.1% and
      94.8%, respectively, which were directly used for NMR analyses.

PMID- 18723180
TI  - Determination of mycophenolic acid in meat products using mixed mode reversed
      phase-anion exchange clean-up and liquid chromatography-high-resolution mass
      spectrometry.
AB  - A method for determination of mycophenolic acid (MPA) in dry-cured ham, fermented
      sausage and liver pate is described. MPA was extracted from meat with bicarbonate
      acetonitrile, further cleaned-up by mixed mode reversed phase-anion exchange and
      detected using a LC-MS system with electrospray ionisation-time-of-flight
      detection. The limit of detection was 4 microg/kg in sausage and 6 microg/kg in
      ham and pate. The method was successfully used for quantification of MPA in dry
      cured ham and liver pate artificially inoculated with Penicillium brevicompactum.
      Levels ranged from 190 microg/kg in centre to 11 mg/kg in surface of ham and from
      150 microg/kg in bottom to 14 mg/kg in surface of pate.

PMID- 18723181
TI  - Controlled deposition of calcium carbonate particles on porous membranes by using
      alternating current system.
AB  - The deposition of calcium carbonate particles in the absence of additives was
      performed through the application of an alternating current. Solutions of calcium
      chloride and sodium carbonate were filled in glass cells, and a porous polymer
      membrane was interposed between the glass cells. An alternating current with a
      sine waveform (frequency: 10 Hz) was applied by using a platinum electrode. In
      this process, the reciprocal migration of calcium and carbonate ions toward the
      interface of the pores on the membrane takes place. Moreover, ion mixing occurs
      to a small extent at the interface of the pores. An alternating current was
      applied for 30 min during which the ion mixing continued. When observed using a
      scanning electron microscope, a majority of the formed calcium carbonate
      particles was found to exhibit a spheroidal vaterite crystal structure. This
      crystal structure was confirmed to be vaterite after characterization by X-ray
      diffraction. In the absence of an alternating current, only calcite was formed on
      the porous polymer membrane. Taking this result into account, it was concluded
      that the alternating current could induce reciprocal ion migration through the
      pores of the membrane, and vaterite deposition can be achieved. This is one of
      the methods employed for the calcium carbonate formation on the porous membrane
      by using an alternating current system.

PMID- 18723182
TI  - Thermodynamics of mixed micelles: Determination of the aggregate composition.
AB  - In most studies concerning surfactant mixtures, the determination of the
      composition of mixed micelles is often tricky. This composition can be obtained
      by different ways. One of them, undoubtedly the most used, supposes, a priori,
      that the surfactant in the micelle follows the regular solution model. This poses
      a problem on the thermodynamic point of view because in these studies, a model of
      behavior is first admitted for deducing a composition. In a correct thermodynamic
      approach, a composition should first be determined and then, a model of behavior
      which accounts for the observed physicochemical properties can be found. This
      approach is all the more questionable since the application of the Gibbs-Duhem
      relationship to the pseudo-phase allows aggregate composition to be determined
      simply, without using a solution model, because the composition of the bulk at
      the threshold of aggregation is known. In this article, we describe and validate
      a simple procedure, which supplements that proposed by Rodenas et al. [E.
      Rodenas, M. Valiente, M.D. Villafruela, J. Phys. Chem. B 103 (1999) 4549], and
      which allows determination of the activities of the components of the micellar
      aggregate and its composition. The results are compared to those obtained with
      other approaches such as molecular-thermodynamic model.

PMID- 18723183
TI  - Template assisted synthesis of silica-coated molecular crystal nanorods: From
      hydrophobic to hydrophilic nanorods.
AB  - We report a method for the preparation of silica-coated molecular crystal
      nanorods. A sol-gel method was used to make silica nanotubes inside anodized
      alumina templates. The nanotubes were then loaded with 9-anthracene carboxylic
      acid (9-AC) and solvent annealed to produce silica-coated organic nanorods. The
      core-shell structure was confirmed using electron microscopy, and the highly
      crystalline organic core was characterized using powder X-ray diffraction and
      transmission electron microscopy. The silica-coated 9-AC rods had much improved
      dispersal properties in aqueous solution, and were also able to undergo
      reversible bending under UV illumination, as observed previously for uncoated 9
      AC rods. This work demonstrates that it is possible to make surface-coated
      molecular crystal nanorods that retain their useful functionalities.

PMID- 18723184
TI  - Analysis of compositional data in communication disorders research.
AB  - The study of communication and its disorders often involves coding several
      behaviors and examining the proportions with which individual behaviors are
      produced within data sets. Problems are encountered when studying multiple
      behaviors between data sets, because of the interdependence of the proportions:
      as one coded behavior increases, at least one other must decrease. The
      interdependence of data means that traditional statistical techniques can be used
      to analyse differences in the proportion of only one behavior over time or
      between clinical groups. We describe a statistical technique, previously used in
      geological and biomedical research, which can be used to analyse all behaviors in
      compositional data sets, and give examples of its use with interaction data. The
      technique allows, for the first time, full comparison of entire patterns of
      multiple communication behaviors, both over time and between clinical groups. The
      technique will aid both basic and applied communication research. LEARNING
      OUTCOMES: Readers will understand the advantages and limitations of frequency
      counts and proportions for the analysis of multiple behaviors. Readers will be
      able to analyze change in proportions of multiple behaviors within a data set
      between groups and across time.

PMID- 18723185
TI  - WITHDRAWN: "Pseudo-high lateral leads Brugada pattern" due to lead reversal.
AB  - Available online August 26, 2008 This article has been withdrawn consistent with
      Elsevier Policy on Article Withdrawal
      (http://www.elsevier.com/locate/withdrawalpolicy). The publisher apologizes for
      any inconvenience this may cause.

PMID- 18723186
TI  - Wide complex irregularly regular tachycardia with QRS alternation.
AB  - A 44-year-old white man was referred to our service because of a history of
      symptomatic rapid palpitations that had begun on January 2007. He had no previous
      history of syncope or family history of sudden cardiac death. The patient was
      otherwise well and had not been taking any medications. The electrocardiogram
      (ECG) recorded during sinus rhythm was within normal limits. A 12-lead ECG was
      performed during the last episode on July 2007 while he was working at his
      office. An irregular wide complex tachycardia with varying QRS morphology (left
      bundle-branch block with an alternating pattern) was documented. The differential
      diagnoses based on the 12-lead electrocardiogram (ECG) were supraventricular
      tachycardia with aberrant conduction and QRS alternans, atrial tachycardia with
      anterograde conduction over an accessory pathway, or ventricular tachycardia. An
      electrophysiology study was performed and the results are discussed.

PMID- 18723187
TI  - Prolonged sinus node dysfunction caused by obstruction of the sinus node artery
      occurring during coronary stenting.
AB  - We report a unique case with prolonged sinus node dysfunction caused by
      accidental occlusion of the sinus node artery occurring during coronary stenting
      for a proximal right coronary lesion.

PMID- 18723188
TI  - Prognostic significance of inverse spatial QRS-T angle circadian pattern in
      myocardial infarction survivors.
AB  - BACKGROUND: We investigated the predictive value of the spatial QRS-T angle
      (QRSTA) circadian variation in myocardial infarction (MI) patients. METHODS:
      Analyzing 24-hour recordings (SEER MC, GE Marquette) from 151 MI patients (age 63
      +/- 12.7), the QRSTA was computed in derived XYZ leads. QRS-T angle values were
      compared between daytime and night time. The end point was cardiac death or life
      threatening ventricular arrhythmia in 1 year. RESULTS: Overall, QRSTA was
      slightly higher during the day vs. the night (91 degrees vs. 87 degrees, P =
      .005). However, 33.8% of the patients showed an inverse diurnal QRSTA variation
      (higher values at night), which was correlated to the outcome (P = .001, odds
      ratio 6.7). In multivariate analysis, after entering all factors exhibiting
      univariate trend towards significance, inverse QRSTA circadian pattern remained
      significant (P = .036). CONCLUSION: Inverse QRSTA circadian pattern was found to
      be associated with adverse outcome (22.4%) in MI patients, whereas a normal
      pattern was associated (96%) with a favorable outcome.

PMID- 18723189
TI  - Complete atrioventricular block persisting after regression of infectious
      myocarditis.
AB  - Atrioventricular block is usually transient during the course of infectious
      myocarditis. We report the case of a patient presenting with complete infra
      hisian atrioventricular block occurring in the setting of infectious myocarditis
      and in whom a pacemaker should be finally implanted. Borderline serologies for
      picornavirus were present 6 weeks later. Complete atrioventricular block
      persisted during the two years of follow-up despite otherwise complete regression
      of the myocarditis. We then discuss the main features of conduction disturbances
      complicating infectious myocarditis, including a list as complete as possible of
      all the causal agents possibly involved.

PMID- 18723190
TI  - Intrathecal upregulation of IFN-gamma and MIP-1beta in juvenile muscular atrophy
      of the distal upper extremity.
AB  - Juvenile muscular atrophy of the distal upper extremity (JMADUE) is associated
      with airway allergy and hyperIgEaemia, suggesting the involvement of
      immunological processes. In this study we aimed to clarify the changes in various
      cytokines/chemokines in cerebrospinal fluid (CSF) from JMADUE patients. We
      simultaneously measured 17 cytokines/chemokines in sera and CSF from 6 patients
      with JMADUE before treatment and from 14 patients with cervical spondylosis (CS)
      as a disease control (mean age at examination 23+/-7 and. 57+/-16 years,
      respectively), using a fluorescent bead-based immunoassay. We also assayed CSF
      from a JMADUE patient before and after plasma exchanges. In sera, only an
      increase of MIP-1beta (CCL3) in the JMADUE patients had a marginal significance
      as compared with the CS patients. In the CSF, IFN-gamma and MIP-1beta (CCL3) were
      significantly elevated in JMADUE patients compared with controls (1.5 and 2-fold
      increases, respectively), while no other cytokines/chemokines showed any
      significant differences. Moreover, the upregulated cytokines decreased after
      plasma exchanges in accord with improvement of distal upper limb weakness. The
      intrathecal upregulation of proinflammatory Th1 cytokines/chemokines, such as IFN
      gamma and MIP-1beta (CCL3), in the CSF of JMADUE patients indicates the possible
      involvement of intrathecal immunological processes in this condition.

PMID- 18723191
TI  - Development of a fish-based multimetric index to assess the ecological quality of
      marine habitats: the Marine Fish Community Index.
AB  - In this paper the Marine Fish Community Index (MFCI) for the assessment of
      ecological status of marine environment is proposed. The MFCI was divided into 4
      typologies: Rocky subtidal; shallow, intermediate and deep soft-bottoms. Based on
      the typical community associated to each typology and the DPSIR analysis
      performed, a set of metrics were selected and tested through a multiple
      correlation matrix (Pearson's coefficient) and the core ones included in the
      index. The MFCI was applied in all typologies and the scores obtained with each
      metric were analyzed. In order to test the robustness of the MFCI the final
      ecological value of each zone was recalculated by removing successively one
      metric at a time. The MFCI showed a sensitive and robust response in the
      ecological status assessment. Since it incorporates both functional and
      structural community information, the MFCI can be useful in the context of the
      Marine Strategy Framework Directive as well as in other contexts of conservation
      and sustainable management of the marine environment.

PMID- 18723192
TI  - Efficacy of adapted estuarine fish-based multimetric indices as tools for
      evaluating ecological status of the marine environment.
AB  - The assessment of ecological status of marine fish communities required by the
      marine strategy framework directive (MSFD) emphasises the need for fish-based
      ecological indices in marine waters. In this study we adapt five estuarine
      multimetric indices to the marine environment and apply them in three types of
      substrates, analysing the metrics responsible for the obtained patterns of
      ecological status. The results show inefficiency of the community degradation
      index (CDI) and the biological health index (BHI) in ecological status assessment
      and disagreement between the estuarine biotic integrity index (EBI), the
      estuarine fish community index (EFCI) and the transitional fish classification
      index (TFCI). Analysis of individual metrics suggests lack of representativeness
      and consideration for the particularities of each substrate's typical fish
      communities. None of the tested indices were efficient on the marine environment,
      urging the need for new marine indices that account for differences between types
      of substrate and depth.

PMID- 18723193
TI  - [The transition from childhood to adulthood in neurosurgery: a description].
AB  - The transition from childhood to adulthood is a difficult period for
      neurosurgical patients, who are at risk of interrupted follow-up, causing delayed
      diagnosis of complications and compromised outcome. Many of these patients harbor
      chronic diseases that have an impact on their adult life, may present new
      developments and sometimes decompensate suddenly. The authors review their
      experience with 601 patients treated for hydrocephalus, myelomeningocele, or
      tumors, and followed after their 20th birthday. Mortality, morbidity and
      socioprofessional outcome statistics are provided, showing the magnitude of the
      health problem in this population. The authors then review the obstacles to the
      transition from childhood to adulthood and propose possible solutions. Some
      problems stem from the patient's lack of information, remedied by early
      education. Others involve physicians, whose skills may be fragmented and who lack
      clinical data; this requires greater awareness of this entity, inclusion of
      lectures on this topic in the medical curriculum and increased clinical research
      in this field. Finally, obstacles in hospital organization and healthcare
      financing require that patient support groups and medical societies unite to
      lobby for improvements. The problems related to the transition from childhood to
      adulthood in neurosurgery is a complex one, requiring all participants to be
      involved in the possible solutions. This endeavor should be regarded as an
      integral part of the duties of both pediatric and adult neurosurgeons.

PMID- 18723194
TI  - [Follow-up of adult patients treated during childhood for hydrocephalus].
AB  - The hydrocephalic patient is at risk throughout life of developing complications
      that may be severe or even fatal. The neurological, developmental, social and
      occupational outcome is affected by the sequelae of the initial disease and the
      consequences of intracranial hypertension, but also by imaginary obstacles.
      Unless proved otherwise, the patient with a shunt must be considered shunt
      dependent; shunt independence is rare and must be proved following a rigorous
      protocol. The hydrocephalic patient should therefore be followed regularly and
      for life in neurosurgery to screen for and prevent complications as much as
      possible. Follow-up also allows patient education and coordination by the
      neurosurgeon and other specialists such as the neurologist and the physical
      therapist. Organizing the follow-up of the hydrocephalic patient into adulthood
      is the responsibility of the neurosurgeon in charge; the modalities of this
      follow-up will vary depending on local conditions. The patient should be educated
      on the need for this follow-up and prepared for this transition long before it
      occurs.

PMID- 18723195
TI  - [Follow-up of adult patients with myelomeningocele].
AB  - The adult outcome of spina bifida patients is fraught with multiple problems
      reflecting the multisystemic nature of the disease. These problems result in both
      mortality, actually caused in most cases by the shunt, and morbidity, mostly
      affecting locomotion and sphincter control. These patients can thus lose
      ambulation and suffer from worsening incontinence and kidney function. The result
      in the vast majority of cases is a poor functional and socioprofessional outcome.
      The patients' demands regarding their occupational and affective lives, as well
      as procreation, must be heard. This requires a multidisciplinary approach, and
      pediatric and adult, as well as patient education and financial support for
      maintaining the patient's autonomy and medical acts allowing the viability of
      continued medical care.

PMID- 18723196
TI  - Uptake of the pharmaceutical Fluoxetine Hydrochloride from growth medium by
      Brassicaceae.
AB  - Since the European Union banned disposal of sewage sludge (SS) at sea in 1998 the
      application rate of SS to land has risen significantly. Land application is thus
      possibly an important transport route for SS-associated organic chemicals,
      including pharmaceuticals, to soils and perhaps also to plants. The potential for
      the selective serotonin re-uptake inhibitor, Fluoxetine HCl, to undergo uptake
      into Brassicaceae tissues was therefore investigated in a tissue culture study
      under laboratory conditions for 12 weeks. From growth medium containing 280 ng
      Fluoxetine HCl mL(-1), translocation into Brassica oleracea var. botrytis
      (cauliflower) stems (5% mean uptake of applied burden; 0.49 microg g wet weight(
      1)) and leaves (3% mean uptake; 0.26 microg g wet weight(-1)) was confirmed, but
      no evidence of uptake into the curd was found; other possible explanations of the
      observations are also discussed. Although the data for individual plants were
      highly variable, as was the recovery of spiked internal standard (deuterated
      Fluoxetine HCl), the results nonetheless suggest uptake of Fluoxetine may indeed
      be a potential transport route to plants. A similar study of uptake from soils
      rather than from an artificial medium should now be undertaken, with greater
      numbers of replicates and improved analytical methods. Such studies have already
      demonstrated uptake of some antibiotics from manured soils by a variety of plants
      including Brassicaceae, suggesting that the uptake mechanisms may be more
      general.

PMID- 18723197
TI  - Antitumoral and antileishmanial dioncoquinones and ancistroquinones from cell
      cultures of Triphyophyllum peltatum (Dioncophyllaceae) and Ancistrocladus
      abbreviatus (Ancistrocladaceae).
AB  - From the methanolic extracts of solid callus cultures from two species of the
      closely related palaeotropical plant families Dioncophyllaceae and
      Ancistrocladaceae seven new natural naphthoquinones were isolated, dioncoquinones
      A (4) and B (5) from Triphyophyllum peltatum, and ancistroquinones B (6), C (7),
      D (9), E (10), and F (12) from Ancistrocladus abbreviatus. Their structures were
      elucidated by spectroscopic, chemical, and computational methods. Furthermore,
      the already known naphthoquinones plumbagin (2), droserone (3), malvone A (8),
      and nepenthone A (11) were found in the extract of A. abbreviatus. Dioncoquinones
      A (4) and B (5) showed good - and specific - activity against Leishmania major,
      while they were not active against other protozoic parasites. Moreover, treatment
      with 4 and 5 strongly induced apoptosis in human tumor cells derived from two
      different B cell malignancies, B cell lymphoma and multiple myeloma, without any
      significant toxicity towards normal peripheral mononuclear blood cells.

PMID- 18723198
TI  - Comparison of serum lipid compositions, lipid peroxide, alpha-tocopherol and
      lipoproteins in captive marine mammals (bottlenose dolphins, spotted seals and
      West Indian manatees) and terrestrial mammals.
AB  - Concentrations of serum lipid components, lipid peroxide (LPO) and alpha
      tocopherol and electrophoretic patterns of lipoproteins in serum samples obtained
      from captive marine mammals and terrestrial mammals were compared. Serum
      concentrations of total cholesterol, free fatty acid, and phospholipid in fish
      eating animals were significantly higher than those in manatees and cows. Serum
      LPO and alpha-tocopherol concentrations in the fish-eating animals were also
      significantly higher than those in manatees, cows and dogs. Different patterns of
      densitometric scans of low density lipoprotein (LDL) and a significantly lower
      percentage of LDL were demonstrated in the dolphins compared with the seals, cow
      and dogs. The concentration of LPO was significantly correlated with triglyceride
      and phospholipid concentrations in serum from the dolphins. These results suggest
      that triglyceride and phospholipid are susceptible to oxidative reaction in fish
      eating animals. Evaluation of serum lipids, LPO and alpha-tocopherol
      concentrations is needed for nutritional husbandry for fish-eating animals.

PMID- 18723199
TI  - Canine babesiosis caused by Babesia canis vogeli in rural areas of the State of
      Minas Gerais, Brazil and factors associated with its seroprevalence.
AB  - This epidemiological survey on canine babesiosis was carried out in three
      distinct rural regions (Lavras, Belo Horizonte and Nanuque) of the State of Minas
      Gerais, Brazil. Ticks and blood samples were collected during a dry season
      (Lavras, n=92; Belo Horizonte, n=50; Nanuque, n=102) and the subsequent rainy
      season (Lavras, n=71; Belo Horizonte, n=28; Nanuque, n=66) from dogs living on
      farms. Plasma samples were analyzed by the indirect fluorescent antibody test for
      detection of anti-Babesia canis vogeli antibodies. DNA was extracted from blood
      of serologically positive dogs and molecular characterization of Babesia species
      was performed. Rhipicephalus sanguineus, Amblyomma cajennense and Boophilus
      microplus were the tick species identified in all regions. In Lavras, in addition
      to those tick species, A. tigrinum and A. ovale were also identified. The most
      prevalent tick species was A. cajennense (35.3%), followed by R. sanguineus (19%)
      and B. microplus (4.0%). Dogs living in Nanuque region were more heavily infested
      with ticks than dogs living in Belo Horizonte and Lavras regions. The overall
      frequency of anti-B. c. vogeli antibodies in the canine population in rural areas
      of Minas Gerais was 28.7%, with prevalence rates of 49.0% in Nanuque, 34.0% in
      Belo Horizonte and 3.3% in Lavras. The age of the animals and tick infestation
      were associated with seroprevalence of B. c. vogeli. The sequence analysis showed
      that B. c. vogeli was the only Babesia species present in all three regions. This
      study showed different rates of prevalence and incidence of canine babesiosis
      among the three rural regions sampled in Minas Gerais State. The results point to
      the importance of canine babesiosis in rural areas and to the need for further
      studies related to its transmission and maintenance in nature.

PMID- 18723200
TI  - Effects of mosapride citrate, metoclopramide hydrochloride, lidocaine
      hydrochloride, and cisapride citrate on equine gastric emptying, small intestinal
      and caecal motility.
AB  - OBJECTIVE: Although extensive work has been done to elucidate the beneficial and
      unfavorable effects of gastrointestinal prokinetic agents in humans, little is
      known on the effects of these agents in horses. In this study, we compared the
      effects of mosapride, metoclopramide, cisapride, and lidocaine on equine gastric
      emptying, jejunal and caecal motility and evaluated these agents' adverse drug
      reactions (ADRs). ANIMALS: Seven healthy adult Thoroughbreds. PROCEDURE:
      Mosapride 1.0mg/kg and 2.0mg/kg, metoclopramide 0.2mg/kg, and cisapride 1.0mg/kg
      were dissolved in 100mL distilled water for oral administration. Lidocaine
      1.3mg/kg was mixed with 500 mL saline for a 30-min intravenous infusion. Oral
      administration of 100mL distilled water was used as control. Gastric emptying was
      evaluated using (13)CO(2) breath test, and jejunal and caecal motility was
      assessed by electrointestinography. RESULTS: The present study demonstrates that
      mosapride at doses of 1.0mg/kg and 2.0mg/kg facilitates gastric emptying in
      horses. Improved jejunal motility was observed following administration of
      mosapride (1.0mg/kg and 2.0mg/kg), metoclopramide (0.2mg/kg), and cisapride
      (1.0mg/kg). Similarly, improved caecal motility was observed following
      administration of mosapride (2.0mg/kg). CONCLUSIONS AND CLINICAL RELEVANCE: This
      study shows that among the prokinetic agents studied here, only mosapride
      (2.0mg/kg) promotes jejunal and caecal motility in horses. Considering mosapride
      ADRs profile, it is believed that this compound is useful in the treatment of
      diseases associated with decreased GI motility, including postoperative ileus.

PMID- 18723201
TI  - Susceptibility of different chicken lines to H7N1 highly pathogenic avian
      influenza virus and the role of Mx gene polymorphism coding amino acid position
      631.
AB  - Five chicken lines were experimentally infected with a HPAI H7N1 virus, to
      examine the variation in susceptibility to infection. Three lines showed high
      susceptibility to the virus, while two showed some resistance, with 7 out of 20,
      and 11 out of 15 birds, respectively, remaining healthy and surviving the
      experimental infection. Genotyping for the G/A polymorphism at position 2032 of
      Mx cDNA showed that one line was fixed for the G allele, and two were segregating
      for A and G alleles. Birds in the other two lines were selected to be fixed for
      the A allele. Statistical analyses indicated that the Mx genotype did not affect
      the clinical status or the time course of infection after viral inoculation.

PMID- 18723202
TI  - Measuring and modeling reduction of DDT availability to the water column and
      mussels following activated carbon amendment of contaminated sediment.
AB  - A 28-day accumulation study demonstrated the use of mussel uptake, passive
      samplers, and biodynamic modeling to measure the reduction of
      dichlorodiphenyltrichloroethane (DDT) availability in the water column after the
      addition of activated carbon to contaminated sediment. Sediment collected from
      Lauritzen Channel, Richmond, California (16.5mg total DDT/kg) was mixed with
      either virgin activated carbon or a reactivated carbon for one month, after which
      a 28-day laboratory exposure study was completed. Mussels (Mytilus edulis)
      suspended above activated carbon-treated sediment accumulated significantly less
      total DDT in soft tissue, 91% and 84% for virgin and reactivated carbon,
      respectively, as compared to untreated sediment. Mussel tissue concentrations
      correlated to concentrations in semipermeable membrane devices (SPMDs) and
      polyethylene devices (PEDs) suspended over the same sediments. A biodynamic model
      that incorporated DDT water concentrations, either analytically measured or
      estimated from PED uptake, described mussel accumulation over time. Thus, passive
      samplers in combination with biodynamic modeling may provide an important
      screening tool for assessment of filter-feeding uptake and ecological risk to
      water-dwelling organisms exposed to aqueous phase hydrophobic organic
      contaminants.

PMID- 18723203
TI  - Influence of pipe material and surfaces on sulfide related odor and corrosion in
      sewers.
AB  - Hydrogen sulfide oxidation on sewer pipe surfaces was investigated in a pilot
      scale experimental setup. The experiments were aimed at replicating conditions in
      a gravity sewer located immediately downstream of a force main where sulfide
      related concrete corrosion and odor is often observed. During the experiments,
      hydrogen sulfide gas was injected intermittently into the headspace of partially
      filled concrete and plastic (PVC and HDPE) sewer pipes in concentrations of
      approximately 1,000 ppm(v). Between each injection, the hydrogen sulfide
      concentration was monitored while it decreased because of adsorption and
      subsequent oxidation on the pipe surfaces. The experiments showed that the rate
      of hydrogen sulfide oxidation was approximately two orders of magnitude faster on
      the concrete pipe surfaces than on the plastic pipe surfaces. Removal of the
      layer of reaction (corrosion) products from the concrete pipes was found to
      reduce the rate of hydrogen sulfide oxidation significantly. However, the rate of
      sulfide oxidation was restored to its background level within 10-20 days. A
      similar treatment had no observable effect on hydrogen sulfide removal in the
      plastic pipe reactors. The experimental results were used to model hydrogen
      sulfide oxidation under field conditions. This showed that the gas-phase hydrogen
      sulfide concentration in concrete sewers would typically amount to a few percent
      of the equilibrium concentration calculated from Henry's law. In the plastic pipe
      sewers, significantly higher concentrations were predicted because of the slower
      adsorption and oxidation kinetics on such surfaces.

PMID- 18723204
TI  - Polymer biodegradation: mechanisms and estimation techniques.
AB  - Within the frame of the sustainable development, new materials are being
      conceived in order to increase their biodegradability properties. Biodegradation
      is considered to take place throughout three stages: biodeterioration,
      biofragmentation and assimilation, without neglect the participation of abiotic
      factors. However, most of the techniques used by researchers in this area are
      inadequate to provide evidence of the final stage: assimilation. In this review,
      we describe the different stages of biodegradation and we state several
      techniques used by some authors working in this domain. Validate assimilation
      (including mineralisation) is an important aspect to guarantee the real
      biodegradability of items of consumption (in particular friendly environmental
      new materials). The aim of this review is to emphasise the importance of measure
      as well as possible, the last stage of the biodegradation, in order to certify
      the integration of new materials into the biogeochemical cycles. Finally, we give
      a perspective to use the natural labelling of stable isotopes in the environment,
      by means of a new methodology based on the isotopic fractionation to validate
      assimilation by microorganisms.

PMID- 18723205
TI  - Absorption of nitro-polycyclic aromatic hydrocarbons by biomembrane models:
      effect of the medium lipophilicity.
AB  - To demonstrate the relationship between the structure of nitro-polycyclic
      aromatic hydrocarbons and their effect on biomembranes, we have investigated the
      influence of three structurally different nitro-polycyclic aromatic hydrocarbons,
      2-nitrofluorene, 2,7-dinitrofluorene and 3-nitrofluoranthene, on the thermotropic
      behavior of dimyristoylphosphatidylcholine multilamellar vesicles, used as
      biomembrane models, by means of differential scanning calorimetry. The obtained
      results indicate that the studied nitro-polycyclic aromatic hydrocarbons affected
      the thermotropic behavior of multilamellar vesicles to various extents, modifying
      the pretransition and the main phase transition peaks and shifting them to lower
      temperatures. The effect of the aqueous and lipophilic medium on the absorption
      process of these compounds by the biomembrane models has been also investigated
      revealing that the process is hindered by the aqueous medium but strongly allowed
      by the lipophilic medium.

PMID- 18723206
TI  - Predicting soil quality indices with near infrared analysis in a wildfire
      chronosequence.
AB  - We investigated the power of near infrared (NIR) analysis for the quantitative
      assessment of soil quality in a wildfire chronosequence. The effect of wildfire
      disturbance and soil engineering activity of earthworms on soil organic matter
      quality was first assessed with principal component analysis of NIR spectra.
      Three soil quality indices were further calculated using an adaptation of the
      method proposed by Velasquez et al. [Velasquez, E., Lavelle, P., Andrade, M.
      GISQ, a multifunctional indicator of soil quality. Soil Biol Biochem 2007; 39:
      3066-3080.], each one addressing an ecosystem service provided by soils: organic
      matter storage, nutrient supply and biological activity. Partial least squares
      regression models were developed to test the predicting ability of NIR analysis
      for these soil quality indices. All models reached coefficients of determination
      above 0.90 and ratios of performance to deviation above 2.8. This finding
      provides new opportunities for the monitoring of soil quality, using NIR scanning
      of soil samples.

PMID- 18723207
TI  - Field experiment on spray drift: deposition and airborne drift during application
      to a winter wheat crop.
AB  - A field experiment was performed to evaluate various techniques for measuring
      spray deposition and airborne drift during spray application to a winter wheat
      crop. The application of a spraying agent containing the fluorescent dye
      Brilliant Sulfo Flavine by a conventional boom sprayer was done according to good
      agricultural practice. Deposition was measured by horizontal collectors in
      various arrangements in and outside the treated area. Airborne spray drift was
      measured both with a passive and an active air collecting system. Spray deposits
      on top of the treated canopy ranged between 68 and 71% of the applied dose and
      showed only small differences for various arrangements of the collectors.
      Furthermore, only small variations were measured within the various groups of
      collectors used for these arrangements. Generally, the highest spray deposition
      outside the treated area was measured close to the sprayed plot and was
      accompanied by a high variability of values, while a rapid decline of deposits
      was detected in more remote areas. Estimations of spray deposits with the IMAG
      Drift Calculator were in accordance with experimental findings only for areas
      located at a distance of 0.5-4.5 m from the last nozzle, while there was an
      overestimation of a factor of 4 at a distance of 2.0-3.0 m, thus revealing a high
      level of uncertainty of the estimation of deposition for short distances.
      Airborne spray drift measured by passive and active air collecting systems was
      approximately at the same level, when taking into consideration the collector
      efficiency of the woven nylon wire used as sampling material for the passive
      collecting system. The maximum value of total airborne spray drift for both spray
      applications (0.79% of the applied dose) was determined by the active collecting
      system. However, the comparatively high variability of measurements at various
      heights above the soil by active and passive collecting systems revealed need for
      further studies to elucidate the spatial pattern of airborne spray drift.

PMID- 18723208
TI  - Prognostic significance of cancer volume involving seminal vesicles in patients
      with pT3bpN0 prostate cancer.
AB  - OBJECTIVES: To investigate the prognostic effect of the prostate cancer (PCa)
      volume involving the seminal vesicles (CVSVs) in the radical prostatectomy
      specimen from patients with Stage pT3bpN0 PCa. METHODS: We retrospectively
      reviewed the clinical records of 27 patients with Stage pT3bpN0 PCa who had
      undergone radical prostatectomy alone. We measured the CVSVs using a grid method
      on the glass slide under microscopic inspection and investigated the association
      of the CVSVs with clinicopathologic variables. RESULTS: Prostate-specific antigen
      (PSA) failure was confirmed in 11 of the 27 patients (41%) during a median follow
      up of 34 months. The 3-year PSA failure-free survival rate was 48%. The median
      CVSVs was 1.14 cm(3). On univariate analysis, a CVSVs of >1.63 cm(3) was
      associated with positive surgical margins (P = .018), bilateral seminal vesicle
      involvement (P = .03), a long maximal tumor dimension (P = .031), and a greater
      preoperative PSA level (P = .0007). The 3-year PSA failure-free survival rate for
      those with a CVSVs of <or=1.63 cm(3) vs >1.63 cm(3) was 80% and 0%, respectively
      (P = .0009). On multivariate analysis, only the PSA level and CVSVs were
      identified as significant and independent predictors of PSA failure. Stratifying
      patients into 3 risk groups by these predictors, the PSA failure-free survival
      rate for patients with a PSA level >or=10 ng/mL and a CVSVs of >1.63 cm(3) was
      significantly worse than for any other group. CONCLUSIONS: The CVSVs is useful
      and invaluable as an independent predictor of PSA failure in patients with Stage
      pT3bpN0 PCa. The measurement of the CVSVs is simple and helped to determine the
      indication for adjuvant treatment after radical prostatectomy.

PMID- 18723209
TI  - Metastatic renal cell cancer in a 20-year-old pregnant woman.
AB  - We report unusual magnetic resonance imaging findings of a 20-year-old pregnant
      woman at 18 weeks of gestation who was diagnosed with metastatic renal cell
      cancer (RCC) with a large liver metastasis.

PMID- 18723210
TI  - Magnetic resonance imaging of partial segmental priapism (segmental thrombosis of
      corpus cavernosum).
AB  - Partial segment priapism or segmental thrombosis of the corpus cavernosum is a
      rare urologic condition reported 23 times in the world literature. We present the
      clinical and radiologic findings of a 22-year-old man who presented 7 days after
      the onset of symptoms in whom the diagnosis was confirmed with magnetic resonance
      imaging. He was treated conservatively with a nonsteroidal anti-inflammatory drug
      and aspirin with full restoration of erectile function. On the basis of previous
      reports and our own experience, we suggest that the management of partial segment
      priapism should include diagnosis with magnetic resonance imaging and
      conservative treatment with analgesics and an anti-inflammatory drug to control
      symptoms.

PMID- 18723211
TI  - Detailed analysis of Charlson comorbidity score as predictor of mortality after
      radical prostatectomy.
AB  - OBJECTIVES: To investigate the prognostic significance of the individual
      conditions contributing to the Charlson comorbidity score in patients selected
      for radical prostatectomy. METHODS: A total of 1910 consecutive patients who
      underwent radical prostatectomy from 1992 to 2004 were studied. The Charlson
      score and its contributing single conditions were analyzed, and the patients were
      stratified into 3 age groups. Comorbid (noncancer), competing (nonprostate
      cancer), and overall mortality were used as the study endpoints. Mantel-Haenszel
      hazard ratios and Kaplan-Meier survival curves were calculated. Comparisons were
      made using the log-rank test. RESULTS: Eleven comorbid conditions were
      significant predictors of any type of mortality in the different age groups.
      Eight conditions (congestive heart failure, peripheral vascular disease,
      cerebrovascular disease, diabetes, hemiplegia, moderate or severe renal disease,
      diabetes with end organ damage, moderate or severe liver disease, and metastatic
      solid tumor) were significant predictors of overall mortality. Two conditions
      (moderate or severe renal disease and metastatic solid tumor) were significant
      predictors of overall mortality in patients <63 years old. Five conditions
      (myocardial infarction, congestive heart failure, hemiplegia, moderate or severe
      renal disease, and diabetes with end organ damage) were significant predictors in
      patients aged 63-69 years, and 3 (peripheral vascular disease, cerebrovascular
      disease, and moderate or severe liver disease) were significant in patients aged
      >or=70 years. CONCLUSIONS: In patients selected for radical prostatectomy, the
      Charlson score can also predict the mortality risk in those >70 years of age. The
      selection for good risks alters, however, the prognostic weight of the individual
      comorbid diseases in this age group.

PMID- 18723212
TI  - Adoptive transfer of tumor-reactive transforming growth factor-beta-insensitive
      cytolytic T cells for treatment of established mouse Renca tumors.
AB  - OBJECTIVES: To test, using a mouse renal cancer, Renca, whether adoptive transfer
      of tumor-reactive transforming growth factor (TGF)-beta-insensitive cytolytic T
      cells can inhibit tumor progression. METHODS: Cytolytic T cells were isolated
      from the spleen of male Balb/c mice repeatedly primed with irradiated Renca
      cells. They were expanded ex vivo and were rendered TGF-beta-insensitive by
      infecting with a retrovirus containing dominant negative TGF-beta type II
      receptor. RESULTS: These tumor reactive TGF-beta-insensitive cytolytic T cells
      showed a specific and robust tumor killing activity against Renca cells, but not
      irrelevant cells, using an in vitro cytotoxic assay. Adoptive transfer of
      cytolytic T cells was performed in mice 10 days after they were challenged with
      Renca cells (5 x 10(5)) by tail vein injection. At 30 days after the adoptive
      transfer, the pulmonary tumor counts in mice who had received TGF-beta
      insensitive cytolytic T cells (mean +/- standard deviation 130 +/- 140) was
      significantly less than those in mice that had received TGF-beta-sensitive
      cytolytic T cells (305 +/- 60) or in mice had received naive cytolytic T cells
      (375 +/- 50; P < .01). Kaplan-Meier survival analysis indicated that mice that
      had received adoptive transfer of TGF-beta-insensitive cytolytic T cells had a
      significantly greater rate of survival (75%) compared with mice that had received
      TGF-beta-sensitive cytolytic T cells (35%) or naive cytolytic T cells (15%),
      respectively (P < .05). CONCLUSIONS: These results suggest that adoptive transfer
      of tumor-reactive TGF-beta-insensitive cytolytic T cells can warrant
      consideration for renal cell cancer immunotherapy.

PMID- 18723213
TI  - Laterally extended endopelvic resection (LEER)--principles and practice.
AB  - Exenteration has been used for the last 6 decades, mainly to treat cancers of the
      lower and middle female genital tract in the irradiated pelvis. New ablative
      techniques based on developmentally derived surgical anatomy termed laterally
      extended endopelvic resection (LEER) aim to increase the curative resection rate,
      even of tumors extending to and fixed to the pelvic side wall. LEER is performed
      as a combination of at least two of the following procedures: total mesorectal
      excision, total mesometrial resection, and total mesovesical resection. In cases
      of lateral tumor fixation, the inclusion of pelvic side wall and floor muscles,
      such as the obturator internus muscle and pubococcygeus, iliococcygeus and
      coccygeus muscles, and eventually of the internal iliac vessel system assures the
      completeness of the multicompartmental resection. One hundred patients with
      locally advanced (n=25) and recurrent (n=75) gynecologic tumors have been treated
      with these new procedures. In 76 patients, the tumors were fixed to the pelvic
      side wall. Two patients with advanced age and extensive comorbidity died during
      the early postoperative period. Moderate and severe treatment-related morbidity
      was 70%, mainly due to compromised healing of irradiated tissue and the
      performance of complex reconstructions. At a median follow-up period of 30 months
      (range, 1-136 months), 5-year recurrence-free and disease-specific overall
      survival probabilities are 62% (95% CI, 52-72%) and 55% (95% CI, 43-67%),
      respectively. LEER has significant potential to salvage selected patients with
      locally advanced and recurrent gynecologic malignancies, including those with
      pelvic side wall disease, traditionally not considered for surgical therapy.

PMID- 18723214
TI  - Ascites from epithelial ovarian cancer contain high levels of functional decoy
      receptor 3 (DcR3) and is associated with platinum resistance.
AB  - OBJECTIVE: Decoy receptor 3 (DcR3), a soluble tumor necrosis factor receptor is a
      known binding partner of multiple apoptotic ligands inhibiting apoptosis. The
      expression of DcR3 by cancers has been reported in gastrointestinal cancers yet
      it has not been described in ovarian cancer. Abnormalities in apoptosis pathways
      are seen in ovarian cancer and we theorized that the presence of DcR3 is a
      component of the dysregulation. METHODS: Ascites samples from 44 women with
      advanced ovarian cancer were tested for DcR3 by ELISA. The ability of ascites to
      inhibit Fas-ligand mediated apoptosis was determined by chromium release assays
      using cell surface or soluble Fas-ligand. Clinical parameters including, response
      to platinum and progression free and overall survival were compared between
      patients with high or low levels of DcR3. RESULTS: DcR3 was found in all 44 cases
      by ELISA. Ascites fluid significantly inhibited Fas-ligand mediate apoptosis
      using both surface Fas-ligand (KFL-9 cells) and soluble Fas-ligand. Blocking DcR3
      with antibodies restores the cytolytic effects in both assays. HIGH DcR3 level
      was associated with stage IV disease and more than double the incidence of
      platinum resistant disease. In this modest sample size Low DcR3 cases had longer
      PFI and overall survival however neither difference was statistically
      significant. CONCLUSIONS: DcR3 is expressed by epithelial ovarian cancers,
      concentrated in ascites and inhibits Fas-ligand mediated apoptosis. Together with
      a trend toward poor patient outcome these results indicate that expression of
      DcR3 by ovarian cancers is worthy of further investigation in a larger population
      to allow multivariate analysis.

PMID- 18723215
TI  - Computer-assisted semen analysis and its utility for profiling boar semen
      samples.
AB  - Achieving and maintaining a successful swine AI program depends on a number of
      factors, including accurate semen evaluation, typically sperm motility,
      morphology and concentration. Computer-Assisted Semen Analysis or CASA (i.e.,
      image analysis with a phase-contrast microscope and computer measurements of
      motion parameters) objectively evaluates sperm motion characteristics, morphology
      and concentration. A total of 3077 semen collections were evaluated with CASA (on
      the day of collection), and a semen dose subset was used for single-sire AI of
      6266 females over 6 months. Fertility data from these inseminations were fitted
      with models including farm/stud, line, boar, parity, mating week, semen age at
      mating and boar age at mating. The residuals from these models showed no
      correlation for any CASA semen unique motion parameter, which could be due to the
      level of sperm concentration, the number of inseminations per estrus, and the low
      number of females mated per boar. Future studies to expand CASA/fertility
      analysis need to address these constraints and may include analysis of extended
      boar semen after storage for 1 week.

PMID- 18723216
TI  - Effects of scrotal insulation in Nellore bulls (Bos taurus indicus) on seminal
      quality and its relationship with in vitro fertilizing ability.
AB  - The objectives of this study were to assess the effects of induced testicular
      degeneration in Bos taurus indicus (Nellore) bulls on changes in seminal
      characteristics and fertilizing ability of sperm. Four Nellore bulls (30-36-month
      old, 500-550 kg) with good seminal quality (>80% motile and morphologically
      normal sperm) had scrotal insulation applied for 5d. Semen was collected by
      electroejaculation and cryopreserved at the pre-insulation moment, and 7, 14, and
      21 d after insulation was removed. Gross motility, vigor of sperm movement (1-5),
      acrosome integrity, sperm morphology (phase-contrast microscopy), nuclear
      vacuoles and abnormal chromatin (Feulgen-stain) were determined after sperm
      preparations for in vitro fertilization (IVF). Prior to IVF, sperm were separated
      using a Percoll gradient (45% and 90%). Normal sperm decreased (P<0.05) 14 and 21
      d after insulation was removed. On 14 and 21 d, the incidence of head defects
      (9.7 +/- 0.6 and 17.0 +/- 0.8, respectively; mean +/- S.E.M.) was higher (P<0.05)
      in agreement with the incidence of nuclear vacuoles (14.0 +/- 5.0 and 12.3 +/-
      2.3) and abnormal chromatin (24.4 +/- 7.2 and 30.8 +/- 2.8). Although the
      frequency of cleaved oocytes decreased only on 21 d (P<0.05), blastocyst rates
      were lower (P<0.05) than pre-insulation on 14 and 21 d. In regression analyses,
      only nuclear vacuoles, head defects and intact acrosome accounted for differences
      in cleavage (R2=0.38, 0.48, and 0.30, respectively) and blastocyst rates
      (R2=0.35, 0.37, and 0.44). Abnormal chromatin was associated only with blastocyst
      rates (R2=0.35). In conclusion, blastocyst rate was more sensitive than cleavage
      rate and the assessment of nuclear integrity is recommended to predict the
      fertilizing ability of bull sperm.

PMID- 18723217
TI  - XDR tuberculosis can be cured with aggressive treatment.

PMID- 18723218
TI  - Treatment of extensively drug-resistant tuberculosis in Tomsk, Russia: a
      retrospective cohort study.
AB  - BACKGROUND: Mycobacterium tuberculosis strains that cause untreatable drug
      resistant disease are a threat worldwide. We describe the treatment, management,
      and outcomes of patients with extensively drug-resistant tuberculosis in Tomsk,
      Russia. METHODS: We undertook a retrospective cohort study of 608 patients with
      multidrug resistant tuberculosis who had treatment in civilian or prison
      services, between Sept 10, 2000, and Nov 1, 2004, according to the treatment
      strategy recommended by WHO. Clinical characteristics, management practices, and
      treatment outcomes of patients with extensively drug-resistant (XDR) tuberculosis
      and non-extensively drug-resistant (non-XDR) tuberculosis are described. The main
      outcome was the frequency of poor and favourable outcomes at the end of
      treatment. FINDINGS: Of 608 patients with multidrug resistant tuberculosis, 29
      (4.8%) patients had baseline XDR tuberculosis. Treatment failure was more common
      in patients with XDR tuberculosis than in those with non-XDR tuberculosis (31%vs
      8.5%, p=0.0008). 48.3% of patients with XDR tuberculosis and 66.7% of patients
      with non-XDR tuberculosis had treatment cure or completion (p=0.04). The
      frequency and management of adverse events did not differ between patients with
      XDR and non-XDR tuberculosis. INTERPRETATION: The chronic features of
      tuberculosis in these patients suggest that extensively drug-resistant
      tuberculosis may be acquired through previous treatments that include second-line
      drugs. Aggressive management of this infectious disease is feasible and can
      prevent high mortality rates and further transmission of drug-resistant strains
      of Mycobacterium tuberculosis.

PMID- 18723219
TI  - Use of hybrid chitosan membranes and N1E-115 cells for promoting nerve
      regeneration in an axonotmesis rat model.
AB  - Many studies have been dedicated to the development of scaffolds for improving
      post-traumatic nerve regeneration. The goal of this study was to develop and test
      hybrid chitosan membranes to use in peripheral nerve reconstruction, either alone
      or enriched with N1E-115 neural cells. Hybrid chitosan membranes were tested in
      vitro, to assess their ability in supporting N1E-115 cell survival and
      differentiation, and in vivo to assess biocompatibility as well as to evaluate
      their effects on nerve fiber regeneration and functional recovery after a
      standardized rat sciatic nerve crush injury. Functional recovery was evaluated
      using the sciatic functional index (SFI), the static sciatic index (SSI), the
      extensor postural thrust (EPT), the withdrawal reflex latency (WRL) and ankle
      kinematics. Nerve fiber regeneration was assessed by quantitative stereological
      analysis and electron microscopy. All chitosan membranes showed good
      biocompatibility and proved to be a suitable substrate for plating the N1E-115
      cellular system. By contrast, in vivo nerve regeneration assessment after crush
      injury showed that the freeze-dried chitosan type III, without N1E-115 cell
      addition, was the only type of membrane that significantly improved posttraumatic
      axonal regrowth and functional recovery. It can be thus suggested that local
      enwrapping with this type of chitosan membrane may represent an effective
      approach for the improvement of the clinical outcome in patients receiving
      peripheral nerve surgery.

PMID- 18723220
TI  - Measuring and modelling mixture toxicity of imidacloprid and thiacloprid on
      Caenorhabditis elegans and Eisenia fetida.
AB  - While the standard models of concentration addition and independent action
      predict overall toxicity of multicomponent mixtures reasonably, interactions may
      limit the predictive capability when a few compounds dominate a mixture. This
      study was conducted to test if statistically significant systematic deviations
      from concentration addition (i.e. synergism/antagonism, dose ratio- or dose level
      dependency) occur when two taxonomically unrelated species, the earthworm Eisenia
      fetida and the nematode Caenorhabditis elegans were exposed to a full range of
      mixtures of the similar acting neonicotinoid pesticides imidacloprid and
      thiacloprid. The effect of the mixtures on C. elegans was described significantly
      better (p<0.01) by a dose level-dependent deviation from the concentration
      addition model than by the reference model alone, while the reference model
      description of the effects on E. fetida could not be significantly improved.
      These results highlight that deviations from concentration addition are possible
      even with similar acting compounds, but that the nature of such deviations are
      species dependent. For improving ecological risk assessment of simple mixtures,
      this implies that the concentration addition model may need to be used in a
      probabilistic context, rather than in its traditional deterministic manner.

PMID- 18723221
TI  - Cellular and humoral immune responses during intrathoracic paracoccidioidomycosis
      in BALB/c mice.
AB  - Paracoccidioidomycosis is a chronic infection that primarily affects the lungs.
      Here we investigated cellular and humoral immune responses after intrathoracic
      Paracoccidioidesbrasiliensis infection in BALB/c mice. P. brasiliensis-colony
      forming units (CFUs), fungal DNA and granulomas in lungs increased progressively,
      peaking at day 90 postinfection (p.i.). IFN-gamma production was highest on day
      15 p.i., declining thereafter. The kinetics of the NO production was similar to
      that described for IFN-gamma. In contrast, IL-10 increased from day 45 p.i.
      reaching a peak at day 90. Levels of serum IgG1 were higher than IgG2a between
      days 30 and 90 p.i. 30% of mice died by day 90 p.i. These data indicate that
      infection with P. brasiliensis by the intrathoracic route shows high IFN-gamma
      and NO production at day 15 p.i., unable to control multiplication of fungi,
      which appears to be associated with a progressive increase in IL-10 and in the
      number and complexity of granulomas.

PMID- 18723222
TI  - Arsenic contamination of groundwater in the Terai region of Nepal: an overview of
      health concerns and treatment options.
AB  - A review of published information on the arsenic contamination of groundwater in
      the Terai regions of Nepal showed that the source was mainly geogenic due to the
      dissolution of the arsenic-bearing minerals. Clinical observations of patients in
      the arsenic affected districts revealed chronic arsenic poisoning from drinking
      water. Half a million people inhabiting the region are believed to have been
      exposed to arsenic levels greater than 50 microg/L in their drinking water.
      Thirty-one percent of the population (3.5 million) in the region are estimated to
      have been exposed to arsenic levels between 10 and 50 microg/L. Iron assisted
      biosand filters currently distributed and in operation are a suitable alternative
      to mitigate the interim arsenic standard of 50 microg/L, as set by the Nepal
      Government. Arsenic biosand filters were also effective in removing bacteria and
      viruses from drinking water in laboratory and field tests. However, groundwater
      treatment targeting cluster communities in the Terai region is the sustainable
      way of mitigating the arsenic problem.

PMID- 18723223
TI  - Stopping time: Henry Fox Talbot and the origins of freeze-frame photography.
AB  - As an image-making tool for scientists studying the transient, instantaneous
      photography has long been seen as opening up a visual realm previously
      inaccessible to the inferior testimony of the human eye. But when photographic
      pioneer Henry Fox Talbot took the first photograph of a moving object by the
      light of an electric spark in 1851, he was guided by existing visual practices
      designed to create instantaneous vision in the eye itself. Exploring the
      background behind the peculiar subject of his experiment - a mechanically
      spinning disc - reveals a hidden prehistory of spark-illuminated photography:
      physicists' pre-photographic techniques for stopping time.

PMID- 18723224
TI  - Brefeldin A inhibits vesicular MHC class I processing in resting but not in CpG-
      and disruption-activated DC.
AB  - Dendritic cells (DC) can process exogenous proteins for presentation on MHC class
      I (MHC-I) in a vesicular pathway (VP) that is distinct from the classical,
      cytosolic MHC-I pathway. Here we investigate the sensitivity of this VP to
      Brefeldin A (BFA), a fungal metabolite which inhibits vesicular trafficking by
      preventing the activation of some ADP-ribosylation factor (ARF) proteins, in both
      resting and differently activated DC. The VP could be directly visualized in DC
      by the presence of OVA-derived H-2K(b)/SIINFEKL complexes in a LAMP1 positive,
      but EEA negative, compartment in wt but not in cathepsin S(-/-) mice as these are
      unable to process OVA into the SIINFEKL peptide in endolysosomes. BFA, which
      binds to specific ARF-GDP-sec7 sites, both in the Golgi and in endolysosomes, was
      found to bind to and inhibit the VP in resting DC. If the VP was selectively
      activated with an immunostimulatory CpG ODN, binding to endolysosomal TLR9
      receptors, or by the mere mechanical disruption of clustered DC cells, BFA no
      longer had this effect. The activation of the VP with both CpG and cellular
      disruption was found to be dependent on the MyD88 adaptor protein. We conclude
      that vesicular MHC-I processing in DC occurs in ARF-regulated LAMP1 positive
      vesicles which, as a consequence of cellular activation, no longer can bind BFA
      and thus become resistant to the inhibitory effect of this drug.

PMID- 18723225
TI  - Resonance Raman spectroscopic studies of hydroperoxo derivatives of cobalt
      substituted myoglobin.
AB  - Recent progress in generating and stabilizing reactive heme protein enzymatic
      intermediates by cryoradiolytic reduction has prompted application of a range of
      spectroscopic approaches to effectively interrogate these species. The impressive
      potential of resonance Raman spectroscopy for characterizing such samples has
      been recently demonstrated in a number of studies of peroxo- and hydroperoxo
      intermediates. While it is anticipated that this approach can be productively
      applied to the wide range of heme proteins whose reaction cycles naturally
      involve these peroxo- and hydroperoxo-intermediates, one limitation that
      sometimes arises is the lack of enhancement of the key intraligand nu(O-O)
      stretching mode in the native systems. The present work was undertaken to explore
      the utility of cobalt substitution to enhance both the nu(Co-O) and nu(O-O) modes
      of the CoOOH fragments of hydroperoxo forms of heme proteins bearing a trans
      axial histidine linkage. Thus, having recently completed RR studies of
      hydroperoxo myoglobin, attention is now turned to its cobalt-substituted
      analogue. Spectra are acquired for samples prepared with (16)O(2) and (18)O(2) to
      reveal the nu(M-O) and nu(O-O) modes, the latter indeed being observed only for
      the cobalt-substituted proteins. In addition, spectra of samples prepared in
      deuterated solvents were also acquired, providing definitive evidence for the
      presence of the hydroperoxo-species.

PMID- 18723226
TI  - The post-tsunami outbreak of diarrhoeal diseases in Car Nicobar Island, India,
      was caused by human group A rotavirus G2 strains.

PMID- 18723227
TI  - The effect of Interceed for reducing adhesion as a middle ear packing agent: an
      experimental study.
AB  - BACKGROUND AND OBJECTIVE: Interceed (oxidized regenerated cellulose) has been
      used to prevent postoperative abdominal adhesion. However, the efficacy and
      safety of using Interceed in middle ear surgery have not been thoroughly studied.
      MATERIALS AND METHODS: The animals were divided into two groups: the Interceed
      group and the Gelfoam (Gelatin sponge) group. In every group, the study was
      performed on five guinea pigs (ten ears). Under the aseptic condition, the middle
      ear mucosa was abraded using a pick through a myringotomy incision. Interceed and
      Gelfoam were then packed into the guinea pigs' middle ear cavities. The auditory
      brainstem responses (ABRs) were assessed preoperatively and at 3 weeks after the
      operation with the animals under general anesthesia. Histopathologic study was
      performed 3 weeks after the operation. RESULTS: The ABR results on postoperative
      week 3 showed no statistically significant difference for myringotomy and
      postpacking. The fibrosis, middle ear mucosa thickening and adhesion formation
      appeared to be less in the Interceed group compared with the Gelfoam group. Any
      foreign body reaction was not observed in the Interceed group. CONCLUSION: Our
      results show that Interceed is nonototoxic and biocompatible with the guinea
      pig's middle ear cavity. Therefore, these results suggest that Interceed could be
      used safely in the middle ear as a middle ear packing agent during otosurgery.

PMID- 18723228
TI  - Adenoidectomy outcomes in pediatric rhinosinusitis: a meta-analysis.
AB  - OBJECTIVE: To evaluate the currently available literature regarding the reported
      effectiveness of adenoidectomy alone in the management of medically refractory
      pediatric chronic rhinosinusitis. METHODS: The MEDLINE and EMBASE databases were
      systematically searched for English language manuscripts reporting on
      effectiveness of adenoidectomy alone in management of medically refractory
      pediatric rhinosinusitis. Additional manuscripts were identified by manual
      searching. Random effects modeling was performed to produce summary estimates of
      adenoidectomy effectiveness. RESULTS: Nine studies met the inclusion criteria.
      Six were cohort studies (level 2b) and four were case series (level 4). Mean
      sample size was 46 subjects (range = 10-121) with grand mean age of 5.8 years
      (range 4.4-6.9 years). All studies showed that sinusitis symptoms or outcomes
      improved in half or more patients after adenoidectomy. Eight studies were
      sufficiently similar to undergo meta-analysis. The summary estimate of the
      proportion of patients who significantly improved after adenoidectomy was 69.3%
      (95% CI = 56.8-81.7%, p < 0.001). The possibility of author bias was explored as
      one author group contributed a large proportion of patients to the study group.
      CONCLUSION: Adenoidectomy reduces caregiver reported symptoms of chronic
      rhinosinusitis in a majority of pediatric patients. Given its simplicity, low
      risk profile, and apparent effectiveness, adenoidectomy should be considered
      first line therapy for medically refractory, uncomplicated pediatric
      rhinosinusitis.

PMID- 18723230
TI  - No effects of human ghrelin on cardiac function despite profound effects on body
      composition in a rat model of heart failure.
AB  - BACKGROUND: Ghrelin, was observed to have treatment-potential for severe chronic
      heart failure (CHF) and cardiac cachexia based on anti-cachectic and cardio
      protective effects. METHODS: We performed two studies to assess the effects of
      human ghrelin on food intake, body weight and body composition, as well as heart
      function in a rat model of CHF. Study-1 (50 or 500 nmole/kg/d ghrelin by pump
      infusion) was focused on food intake and body composition, study-2 (50 or 100
      nmole/kg/d ghrelin by subcutaneous injection (3-times daily) was focused on heart
      function due to a lack of cardiac effects observed in study-1. In both studies,
      myocardial infarction was induced by LAD ligation. On day 28 after surgery, rats
      were randomized and treated with ghrelin or placebo for 4 weeks. Food intake
      (study-1), body composition (NMR) cardiac function (echocardiography and invasive
      hemodynamics (study-2 only) were assessed. RESULTS: In study-1, CHF rats treated
      with high dose ghrelin showed an increase in body weight (+25%, p<0.001), lean
      mass (+16%, p<0.01) and fat mass (+17%, p=0.001) vs placebo. In study-2, CHF rats
      treated with both low- and high dose ghrelin showed an increase in body weight
      (both +18%, p</=0.001), lean mass (both +25%, p<0.001) and fat mass (50
      nmole/kg/d: +43%, p<0.05; 100 nmole/kg/d: +45%, p<0.01) vs placebo. However, no
      beneficial effect of ghrelin treatment on left ventricular ejection fraction or
      change of LV diameters was observed in either study. CONCLUSION: Ghrelin
      treatment results in dose-dependent beneficial effects on body weight and body
      composition, but does not improve cardiac function.

PMID- 18723231
TI  - Muscle sympathetic nerve activity in patients with Chagas' disease.
AB  - BACKGROUND: The progression of heart failure in Chagas' disease has been
      explained by remodeling, leading to neurohumoral activation, or by the direct
      parasite damage to parasympathetic neurons during acute phase, leading to early
      sympathetic activation and progressive heart failure. To help distinguish between
      these hypotheses we studied muscle sympathetic nerve activity (MSNA) at rest and
      during handgrip exercise (30% of maximal voluntary contraction) in patients with
      Chagas' disease and normal ejection fraction vs. patients with heart failure.
      METHODS: A consecutive study of 72 eligible out-patients/subjects was conducted
      between July 1998 and November 2004. The participants were classified in three
      advanced heart failure groups (New York Heart Association Functional Classes II
      III): Chagas' disease (n=15), ischemic (n=15) and idiopathic cardiomyopathy
      (n=15). Twelve Chagas' disease patients without heart failure and normal ejection
      fraction, and 15 normal controls were also studied. MSNA was recorded directly
      from the peroneal nerve by microneurography technique. RESULTS: MSNA was greater
      in heart failure patients when compared with Chagas' disease patients without
      heart failure (51+/-3 vs. 20+/-2 bursts/min P=0.0001). MSNA in Chagas' patients
      with normal ejection fraction and normal controls was not different. During
      exercise, MSNA was similar in all 3 heart failure groups. And, was lower in the
      Chagas' patients with normal ejection fraction than in patients with Chagas'
      disease and heart failure (28+/-1 vs. 63+/-5 bursts/min, respectively).
      CONCLUSION: MSNA is not elevated in patients with Chagas' disease with normal
      ejection fraction. These findings support the concept of remodeling and
      neurohumoral activation as a common pathway following significant cardiac injury.

PMID- 18723232
TI  - Significant left main coronary artery disease from iatrogenic dissection during
      coronary angiography.
AB  - Though atherosclerotic obstruction is the major cause of the obstructive left
      main coronary artery (LMCA) disease, it can be associated with iatrogenic
      dissection during coronary angiography. Here we report a case with severe LMCA
      stenosis due to catheter induced dissection in a 77-year-old man which was
      detected 9 months later. By careful review of the angiogram had taken at 9 months
      ago, the LMCA was injured by the diagnostic left Judkin's catheter during the
      first coronary angiography. The initial lesion was neglected and the dissection
      got worse with time. The patient was successfully treated with two drug-eluting
      stents by crushing technique and discharged without further complication.

PMID- 18723233
TI  - Chronic total occlusion of the left main coronary artery with normal left
      ventricular motion: the occluded site confirmed by three-dimensional computed
      tomography.
AB  - Total occlusion of the left main trunk (LMT) frequently results in sudden cardiac
      death. As a result, it is rarely observed on coronary arteriogram. There are only
      a few reports on chronic total occlusion of the LMT. Most patients present with
      recent, severe angina, but it is not easy to distinguish chronic total occlusion
      of the LMT from other types of severe coronary heart diseases. Here, we report a
      very rare case of chronic total occlusion of the LMT. The patient is a 38-year
      old female with a history of three normal deliveries. Chronic total occlusion of
      the LMT was suspected on coronary arteriogram 2 years previously in the other
      hospital; however, she continued working as a part-time employee at a
      supermarket. She was referred to our hospital because of slightly increased
      effort angina and shortness of breath. The final diagnosis and the site of
      occlusion were determined by three-dimensional computed tomography (3-D CT). The
      patient underwent coronary artery bypass graft (CABG) surgery, and ischemic
      symptoms completely disappeared.

PMID- 18723234
TI  - The use of intra-coronary optical coherence tomography for the assessment of
      sirolimus-eluting stent fracture.
AB  - Drug-eluting stents (DES) have made a tremendous impact on the practice of
      percutaneous coronary intervention. Recently however, long-term DES failures have
      become a focal point, particularly with restenosis and thrombosis. An uncommon,
      yet important cause of DES failure is stent fracture. Of the two established
      first generation DES, the sirolimus-eluting stent (SES) has been particularly
      linked to cases of stent fracture, likely as a result of its closed cell design
      compared with other DES employing an open cell system. We present 2 cases of SES
      fracture confirmed using high-resolution intravascular optical coherence
      tomography giving unique insights into the in-vivo appearance of this
      complication.

PMID- 18723235
TI  - A new frame in thromboembolic cardiovascular disease: Adipocytokine.
AB  - Recent researches have shown that adipocytokines secreted by adipose tissue play
      an important role in inflammation which is considered to be a crucial step in the
      pathogenesis of atherosclerosis. Leptin, one of the earlier adipocytokines, is
      known to play a major role in cardiovascular disease and recent observations
      suggest that leptin is an independent risk factor for coronary heart disease.
      Resistin, another recently discovered adipocytokine, has been related to risk
      factors of atherosclerosis, and in diabetic individuals serum resistin levels
      correlate well with inflammatory markers and are predictive for the development
      of cardiovascular disease. Adiponectin, another adipocytokine of interest in
      recent years, seems to be the most promising one studied to date. In contrast to
      leptin and resistin, adiponectin seems to be beneficial for health and it is a
      protective factor and decreased in obesity. However, many other factors derived
      from adipose tissue have also been discovered, such as interleukin-6, tumor
      necrosis factor alpha, monocyte chemoattractant protein 1, apelin, visfatin and
      probably others awaiting discovery in the near future. In this paper, we
      discussed the role of adipocytokines in the pathogenesis of atherosclerotic
      cardiovascular disease.

PMID- 18723236
TI  - Serosurvey of five viruses in chickens on smallholdings in Bangladesh.
AB  - A serologic survey was undertaken in chickens in smallholdings in Bangladesh for
      avian influenza A virus (AIV), egg drop syndrome '76 virus (EDS'76V), infectious
      bronchitis virus (IBV), Newcastle disease virus (NDV) and reovirus (RV) in three
      phases: January 2002-May 2003, September 2003-August 2004, and August 2005-March
      2006. Four hundred thirty-six sera collected in the 2nd phase, 295 in the first
      phase, 755 in the 1st plus 2nd phases and 295 in the 1st phase were investigated
      for AIV, EDS'76V, IBV and RV, respectively, using enzyme linked immunosorbent
      assays. All 854 sera collected in the three phases were screened for NDV using
      hemagglutination inhibition test. In chickens 20% were seropositive to AIV, 3% to
      EDS'76V, 74% to IBV, 88% to NDV, and 47% to RV. The seroprevalence in flocks was
      23% to AIV, 6% to EDS'76V, 79% to IBV, 89% to NDV and 56% to RV. Twenty-five
      percent chickens had > or = 10log(2)HI titers to NDV.

PMID- 18723238
TI  - Hierarchical organization of the coordinative structure of the skill of clay
      kneading.
AB  - An experiment was conducted to study the skill of clay kneading in pottery. This
      task usually requires a few years to master and is therefore well suited to study
      the long-term development of a complex motor skill. Participants' kneading
      movements were measured in 3D using a motion capture device and phase relations
      among coordinates and joint angles were analyzed in terms of the mutual phase
      relative to a reference point using the Hilbert transform. While a certain degree
      of periodicity was observed in all 10 participants, the behavior of the experts
      was characterized by a significant delay for the right elbow (i.e., the pushing
      arm) and the fore-aft position of the upper torso and only brief delays for the
      other parts, which all tended to synchronize with the reference. These findings
      are consistent with our notion of "differentiation within coordination",
      according to which skill learning proceeds in a hierarchical manner in that
      coordination among limb movements is established first, followed by modulations
      of specific limb movements within the established coordination. Although this
      feature of expert behavior was also apparent in our previous studies of clay
      kneading and samba shaking and dancing, the numbers of participants in those
      studies were not sufficient to draw firm conclusions. Since the present study
      involved more participants and a superior method of analysis, the present
      evidence for the principle of differentiation within coordination is more
      conclusive.

PMID- 18723239
TI  - Yeast diversity in crop-growing environments in Cameroon.
AB  - In the present study, we have investigated the occurrence of yeast flora on
      several agricultural products coming from crop-growing environments in Cameroon,
      to provide better knowledge of the biodiversity of yeast flora, and to thus
      define the impact of this biodiversity on food products. The yeast biodiversity
      was investigated using traditional culture-dependent methods, along with culture
      independent methods. The culture-dependent approach was carried out using both
      direct and enrichment procedures, to detect the broadest possible presence of
      yeast species. A total of 151 strains belonging to 26 different yeast species
      were isolated and identified using restriction pattern analysis of the internal
      transcribed spacer region 5.8S-ITS and sequence analysis of D1/D2 domain of 26S
      rRNA gene. The enrichment isolation procedures carried out in high-sugar media
      allowed the recognition of fermentative species such as Saccharomyces cerevisiae
      and Torulaspora delbrueckii, which have previously not been detected using direct
      isolation methodology. The results of culture-independent method using DGGE
      patterns and sequencing of the DNA bands revealed a lower number of yeast species
      when compared with the culture-dependent methodology even if the identification
      of several yeast species not detected by traditional microbiological procedures
      such as Candida tropicalis and Hanseniaspora uvarum is allowed. Thus, these
      multiphasic approaches to study yeast biodiversity (culture-dependent and 
      independent methods) have allowed us to get a more complete picture of the
      microbial diversity in these natural environments.

PMID- 18723241
TI  - Cutaneous toxoplasmosis after bone marrow transplantation with molecular
      confirmation.
AB  - Toxoplasmosis is a rare and often fatal complication of hematopoietic stem cell
      transplantation (HSCT). The diagnosis of toxoplasmosis is usually made at autopsy
      because of the variety of systemic manifestations and the difficulty of diagnosis
      by serologic methods in the severely immunocompromised patient. Cutaneous
      toxoplasmosis in this setting is extremely rare and is difficult to diagnose with
      certainty because of the morphologic similarity of Toxoplasma gondii to other
      organisms, such as Leishmania and Histoplasma species. We report a patient who
      developed systemic toxoplasmosis, manifested as encephalitis and cutaneous
      lesions, after HSCT. Findings of a skin biopsy led to a tentative histologic
      diagnosis of toxoplasmosis, confirmed by polymerase chain reaction (PCR)
      examination of the skin biopsy and cerebrospinal fluid. This is, to our
      knowledge, the first report of cutaneous toxoplasmosis diagnosed by skin biopsy
      confirmed by PCR and sequencing. This disease may be more common than is
      generally appreciated in severely immunocompromised patients. PCR is a valuable
      adjunct to diagnosis.

PMID- 18723240
TI  - Design, recruitment and baseline results of the ITALUNG trial for lung cancer
      screening with low-dose CT.
AB  - BACKGROUND: Results of randomized clinical trials (RCTs) are needed to assess the
      efficacy of lung cancer screening with low-dose chest computed tomography (CT) in
      reducing lung cancer mortality. We report design and results of enrolment and
      baseline screening test in the ITALUNG trial, a RCT. METHODS: Invitation letters
      were sent to subjects of 55-69 years of age clients of 269 general practitioners.
      Smokers or former smokers of at least 20 pack/years were eligible and after
      written consent were randomized in an active arm undergoing a low-dose CT
      annually for 4 years and in a control arm receiving no screening. Management of
      positive screening test was carried out using follow-up low-dose CT,
      fluorodeoxyglucose positron emission tomography, fine needle aspiration cytology
      and fiber optic bronchoscopy. RESULTS: A sample of 3206 eligible subjects was
      achieved by sending 71,232 letters (enrolment efficacy = 4.5%). Subjects in
      control (n = 1593) and active (n = 1613) arm were balanced for age, gender and
      smoking history. Two-hundred and seven (12.8%) subjects did not undergo CT after
      randomization. The baseline screening test was positive in 426 (30.3%) of 1406
      subjects. Twenty-one lung cancers (prevalence = 1.5%) were found in 20 subjects:
      18 non-small cell lung cancer (NSCLC), 2 small cell lung cancer (SCLC) and a case
      of typical carcinoid. Ten NSCLC (47.6%) were in Stage I. Sixteen fine needle
      aspirations were performed in 15 lung cancers, with a positive result in 12 (75%)
      cases. One biopsy only (6.3%) was performed on a benign lesion. Seventeen lung
      cancers (81%) were treated with surgical resection in 16 subjects. One subject
      underwent surgery for a benign lesion (5.5% of all surgical resections).
      CONCLUSIONS: Recruitment by mail of high risk subjects for a lung cancer
      screening RCT is feasible but not efficient. Results of the baseline screening
      test in the active arm of the ITALUNG trial are substantially in line with those
      of RCT and observational studies.

PMID- 18723242
TI  - The US dermatology workforce: a specialty remains in shortage.
AB  - INTRODUCTION: Since 1999, multiple surveys have documented a stable undersupply
      of dermatologic services in the United States. Factors contributing to the
      imbalance include changes in the demographics of the physician workforce,
      increased demand for services, and a limited number of training positions for new
      physicians. In response to the demand, there has also been a substantial influx
      of nonphysician clinicians into dermatology offices. METHODS: We sought to follow
      up the large data set collected by the American Academy of Dermatology in 2002;
      the survey was repeated in 2005 and 2007. Response rates ranged from 30% to 35%
      and included more than 1200 respondents each year. RESULTS: Few changes were
      noted in the metrics used to assess the balance of supply and demand in the US
      dermatology workforce between 2002 and 2007. Mean wait times for new patient
      appointments decreased slightly from 36 to 33 days. One third of practices
      continue to seek additional dermatologists. In 2007, 23% of practices reported
      employing a physician assistant and 10% a nurse practitioner (up from 15% and 8%
      in 2002). In 2007, typical dermatologists continued to spend the bulk of their
      direct patient care time in medical dermatology (23.9 hours, 63%), followed by
      surgery (10.2 hours, 27%), and then cosmetic dermatology (3.8 hours, 10%). A
      substantial subset of dermatologists (29%) spent half or more of their time in
      surgical and cosmetic dermatology combined. Although female dermatologists worked
      fewer total hours, they spent equal time caring for patients with medical
      dermatologic conditions, less time in surgical dermatology, and more time in
      cosmetic dermatology. LIMITATIONS: The survey is potentially subject to
      inaccurate self-report and response bias. Although the results shed light on
      patient access and the dermatology workforce, they do not establish or quantify
      any impact on patients' health. CONCLUSIONS: Between 2002 and 2007, despite
      continued increases in the number of nonphysician clinicians in US dermatology
      offices, there were only small changes in the overall metrics commonly used to
      assess workforce balance. These findings suggest persistent unmet demand, but,
      given divergent trends of ongoing increases in surgical and cosmetic dermatology,
      growth in the use of physician assistants and nurse practitioners, and an aging
      and expanding US population, the future balance of supply and demand remains
      difficult to predict. Nevertheless, careful workforce planning and deliberative
      consideration of the risks and benefits of rapidly emerging changes in the
      delivery of dermatologic care are essential to ensure access to high-quality care
      for patients with skin disease.

PMID- 18723243
TI  - Risk-adjusted surveillance of hospital-acquired infections in neonatal intensive
      care units: a systematic review.
AB  - Comparisons of bacteraemia incidence between neonatal intensive care units
      (NICUs) can identify centres with effective infection control, whose practices
      can be shared with other units. For fair comparisons, infection incidence must be
      risk-adjusted to control for differences between centres in the vulnerability of
      babies and the intensity of invasive procedures which can introduce infection. We
      reviewed risk adjustment methods for between-NICU comparisons of bacteraemia
      incidence, both in the published literature and in regional and national NICU
      infection monitoring systems. PubMed and Embase were searched for studies
      reporting risk-adjusted bacteraemia incidence in more than one NICU. An internet
      search found NICU infection monitoring systems in Western industrialised
      countries. In all nine studies that met the inclusion criteria, risk adjustment
      reduced but did not eliminate variation in bacteraemia incidence between NICUs.
      In both the studies and the regional monitoring systems, adjustment for baby
      susceptibility generally involved stratification by factors measured at birth.
      Adjustment for Length of stay and invasive procedures involved reporting
      incidence by days with a device, such as central venous catheter days. Methods
      for NICU infection monitoring lack consistency. Adjustment for factors measured
      at birth fails to capture changes in susceptibility throughout admission and
      adjustment for device days does not adequately reflect risk to babies not treated
      with the device. Further research should address variation in risk for all babies
      throughout their NICU stay.

PMID- 18723244
TI  - Pathogenic bacteria in sink exit drains.

PMID- 18723245
TI  - The national nosocomial surveillance network in Hungary: results of two years of
      surgical site infection surveillance.
AB  - In 2004, a secure web-based national nosocomial infection surveillance system was
      established in Hungary. The system, named NNSR (Nemzeti Nosocomialis Surveillance
      Rendszer), is based on the US National Nosocomial Infection Surveillance System
      (NNIS). Surgical procedures, definitions, surveillance methodology and patient
      risk indices are those established by NNIS. In this paper, we present the results
      of the first two years of the surgical patient component of our system. During
      this period, 41 hospitals participated and selected 11 surgical procedures for
      surveillance. Altogether 15812 procedures were surveyed and 360 resulting
      surgical site infections (SSI) were recorded. The overall SSI rate was 2.27%. The
      most commonly selected procedures and corresponding SSI rates were caesarean
      section (1.31%), herniorrhaphy (2.09%), cholecystectomy (1.52%) and hip
      replacement (2.91%). Standardised infection ratios (SIR) were calculated for
      chosen surgical procedures in order to compare against NNIS published rates. SSI
      rates for colonic surgery, caesarean section and mastectomy were lower than
      expected according to the NNIS data but higher for cholecystectomy, herniorrhaphy
      and hip prosthesis infection rates. We intend to recruit more participating
      hospitals, leading to a robust national database that can be used to target
      infection control interventions for patients in Hungary.

PMID- 18723246
TI  - An outbreak of Serratia marcescens septicaemia in neonatal intensive care unit in
      Gaza City, Palestine.
AB  - We performed a case-control study of Serratia marcescens incidence in the
      neonatal intensive care unit of a governmental Gaza Strip hospital from January
      to December 2005. S. marcescens was detected in the blood of 159 confirmed
      nosocomial cases of septicaemia, 70 (44%) neonates died due to S. marcescens
      infection and 89 recovered. The main clinical symptoms were hypothermia 38%;
      jaundice 42%; Apgar score 4 at 1 min in 29% of neonates; and Apgar score 5 at 5
      min in 5%. Risk factors significantly associated with S. marcescens infection
      were birthweight <1,500 g (OR: 1.7; P=0.026); <37 weeks gestational age (OR: 2.0;
      P=0.002); and use of mechanical ventilation (OR: 2.3; P=0.001). Agar diffusion
      susceptibility testing indicated that S. marcescens was generally susceptible to
      imipenem, followed by ciprofloxacin and ofloxacin. We identified potential risk
      factors associated with development of neonatal sepsis and highlight the
      importance of appropriate infection control measures to prevent serious
      infection.

PMID- 18723247
TI  - Evidence-based guidelines for the prevention of ventilator-associated pneumonia:
      results of a knowledge test among European intensive care nurses.
AB  - As part of a needs analysis preceding the development of an e-learning platform
      on infection prevention, European intensive care unit (ICU) nurses were subjected
      to a knowledge test on evidence-based guidelines for preventing ventilator
      associated pneumonia (VAP). A validated multiple-choice questionnaire was
      distributed to 22 European countries between October 2006 and March 2007.
      Demographics included nationality, gender, ICU experience, number of ICU beds and
      acquisition of a specialised degree in intensive care. We collected 3329
      questionnaires (response rate 69.1%). The average score was 45.1%. Fifty-five
      percent of respondents knew that the oral route is recommended for intubation;
      35% knew that ventilator circuits should be changed for each new patient; 38%
      knew that heat and moisture exchangers were the recommended humidifier type, but
      only 21% knew that these should be changed once weekly; closed suctioning systems
      were recommended by 46%, and 18% knew that these must be changed for each new
      patient only; 51% and 57%, respectively, recognised that subglottic drainage and
      kinetic beds reduce VAP incidence. Most (85%) knew that semi-recumbent
      positioning prevents VAP. Professional seniority and number of ICU beds were
      shown to be independently associated with better test scores. Further research
      may determine whether low scores are related to a lack of knowledge, deficiencies
      in training, differences in what is regarded as good practice, and/or a lack of
      consistent policy.

PMID- 18723248
TI  - Enhanced surgical site infection surveillance following caesarean section:
      experience of a multicentre collaborative post-discharge system.
AB  - The caesarean section rate in the UK has more than doubled during the last two
      decades and is continuing to rise. The majority of studies carried out to
      determine the incidence of infection associated with this procedure have been
      restricted to the inpatient stay, which may give misleading results. Women
      undergoing caesarean section have routine contact with a community midwife after
      discharge. This provided an opportunity to assess whether a collaborative
      surveillance approach between hospital and community staff was feasible using
      routinely available information. Following a successful pilot study, 11 maternity
      units in the East Midlands participated in an extended study. Complete records
      were available for 5,563 (88%) women. Overall, 758 (13.6%) wound problems were
      reported, 84% of which developed after discharge. Of these, 488 (8.9%) met
      national definitions for surgical site infection (SSI); however, there was a
      marked inter-unit difference in incidence, ranging from 2.9% to 17.9%.
      Statistical models were used to examine these differences using 12 possible risk
      factors. Five risk factors were found to be significantly associated with the
      development of a surgical site infection: body mass index, age, blood loss,
      method of wound closure and emergency procedures. These results suggest that
      caesarean section is associated with high infectious morbidity, the extent of
      which would have been considerably underestimated without post-discharge
      monitoring. Almost all women with wound problems were treated with antibiotics,
      regardless of how minor the problem, with 97% being prescribed in the community.
      This indicates a requirement for local review of antibiotic prescribing practice.

PMID- 18723249
TI  - A clinical risk index for Clostridium difficile infection in hospitalised
      patients receiving broad-spectrum antibiotics.
AB  - Identification of a population at high risk for Clostridium difficile infection
      (CDI) would enable CDI prevention strategies to be designed. The purpose of this
      study was to create a clinical risk index that would predict those at risk for
      CDI. A CDI risk index was therefore developed, based on a cohort of hospital
      patients given broad-spectrum antibiotics, and divided into a development and
      validation cohort. Logistic regression equations helped identify significant
      predictors of CDI. A scoring algorithm for CDI risk was created using identified
      risk factors and collapsed to create four categories of CDI risk. The area under
      the receiver operating characteristic (aROC) curve was used to measure goodness
      of-fit. Among 54 226 patients, 392 tested positive for C. difficile. Age 50-80
      years [odds ratio (OR: 0.5; P<0.0116)], age >80 years (OR: 2.5; P<0.0001),
      haemodialysis (OR: 1.5; P=0.0227), non-surgical admission (OR: 2.2; P<0.0001) and
      increasing length of stay in the intensive care unit (OR: 2.1; P<0.0001) were
      significantly associated with CDI. A simple risk index using presence of
      significant variables was significantly associated with increasing risk for CDI
      in both development (OR: 3.57; P<0.001; aROC: 0.733) and validation (OR: 3.31;
      P<0.001; aROC: 0.712) cohorts. An OR-derived risk index did not perform as well
      as the simple risk index. This easily implemented risk index should allow
      stratification of patients into risk group categories for development of CDI and
      help fashion preventive strategies.

PMID- 18723250
TI  - Ointments as a source of meticillin-resistant Staphylococcus aureus spread.

PMID- 18723251
TI  - Results of a multicentre randomised controlled trial of statistical process
      control charts and structured diagnostic tools to reduce ward-acquired meticillin
      resistant Staphylococcus aureus: the CHART Project.
AB  - Statistical process control (SPC) charts have previously been advocated for
      infection control quality improvement. To determine their effectiveness, a
      multicentre randomised controlled trial was undertaken to explore whether monthly
      SPC feedback from infection control nurses (ICNs) to healthcare workers of ward
      acquired meticillin-resistant Staphylococcus aureus (WA-MRSA) colonisation or
      infection rates would produce any reductions in incidence. Seventy-five wards in
      24 hospitals in the UK were randomised into three arms: (1) wards receiving SPC
      chart feedback; (2) wards receiving SPC chart feedback in conjunction with
      structured diagnostic tools; and (3) control wards receiving neither type of
      feedback. Twenty-five months of pre-intervention WA-MRSA data were compared with
      24 months of post-intervention data. Statistically significant and sustained
      decreases in WA-MRSA rates were identified in all three arms (P<0.001; P=0.015;
      P<0.001). The mean percentage reduction was 32.3% for wards receiving SPC
      feedback, 19.6% for wards receiving SPC and diagnostic feedback, and 23.1% for
      control wards, but with no significant difference between the control and
      intervention arms (P=0.23). There were significantly more post-intervention 'out
      of-control' episodes (P=0.021) in the control arm (averages of 0.60, 0.28, and
      0.28 for Control, SPC and SPC+Tools wards, respectively). Participants identified
      SPC charts as an effective communication tool and valuable for disseminating WA
      MRSA data.

PMID- 18723252
TI  - Needle protective devices; where are we now?

PMID- 18723253
TI  - Long-term persistence of a single Legionella pneumophila strain possessing the
      mip gene in a municipal shower despite repeated cycles of chlorination.
AB  - The ability of Legionella pneumophila to colonise domestic water systems is a
      primary cause of outbreaks of Legionnaire's disease in humans. World Health
      Organization guidelines recommend that drinking water is chlorinated to between
      0.2 and 1mg/L [Chlorine in drinking-water. Guidelines for drinking-water quality,
      2nd edn. Geneva: World Health Organization; 1996], but L. pneumophila is
      repeatedly isolated from chlorinated water systems, indicating that this
      treatment is not effective at preventing colonisation. Current UK guidelines
      recommend a one-off treatment of 20-50mg/L of free chlorine to remove the
      bacteria. In this study we report on the persistence of L. pneumophila serogroup
      1 in a domestic shower system despite repeated cycles of chlorination at 50mg/L
      for 1h exposure time, over the course of two and a half years. Persisting
      isolates were subjected to in-vitro phenotypic analyses and polymerase chain
      reaction analysis for the toxin-encoding mip gene. Random amplified polymorphic
      DNA typing was also performed to determine whether the isolates recovered on
      different occasions were the same strain. We found that seven isolates of L.
      pneumophila recovered over a two-and-a-half year period are the same genetically
      defined strain, indicating that the bacteria can persist despite repeated cycles
      of chlorination after each successive isolation.

PMID- 18723254
TI  - Pseudomonas aeruginosa biofilms in hospital water systems and the effect of sub
      inhibitory concentration of chlorine.

PMID- 18723255
TI  - Delayed administration of antibiotics and mortality in patients with community
      acquired pneumonia.
AB  - STUDY OBJECTIVE: Previous studies have demonstrated a crude association between
      the time to first antibiotic dose and mortality in patients with community
      acquired pneumonia. We hypothesize that time to first antibiotic dose may affect
      mortality, particularly for patients at high risk of death, that is, patients
      hypoxic on presentation, patients in Pneumonia Severity Index class IV or V, and
      patients older than 65 years at our institution. METHODS: We reviewed data from a
      prospectively collected database of patients with community-acquired pneumonia,
      excluding patients who had received antibiotics before presentation and
      palliative patients not receiving antibiotics. We examined time to first
      antibiotic dose in patients who died or had prolonged length of stay (all
      patients) and in specific subgroups regarded as high risk (age >65 years,
      Pneumonia Severity Index class IV or V, presence of hypoxia or hypotension).
      RESULTS: In 501 patients, the median time to first antibiotic dose was 2.7 hours,
      with 91% of patients receiving antibiotics within 8 hours. Time to first
      antibiotic dose was not positively associated with mortality or prolonged length
      of stay in any of the subgroups examined. We found evidence that patients with
      severe pneumonia received antibiotics earlier than other patients. CONCLUSION:
      Most patients at this institution already receive timely antibiotic therapy. This
      finding may be due to either a true lack of association, in that minor delays in
      antibiotic administration, where antibiotics are generally administered within 8
      hours, do not affect mortality. Additionally, there may be confounding by
      severity, such that patients at highest risk of death received antibiotics
      earlier.

PMID- 18723256
TI  - [HELLP syndrome: the ten commandments].
AB  - The internist has a role to play in the practical approach of HELLP syndrome, a
      disease which can differ according to its symptoms, course and causes. Any recent
      epigastric pain during the end of pregnancy must be considered as a symptom of
      HELLP syndrome. Liver disease together with thrombocytopenia may be present even
      without any renovascular involvement. The disease can be threatening for the
      mother and lead to the foetal death. It can be sometimes difficult to be
      distinguished from thrombotic microangiopathy. Treatment consists mainly in rapid
      discontinuation of pregnancy. Steroid therapy could allow to simplify anaesthesia
      procedures and to avoid blood transfusion. Early-onset HELLP syndrome could be a
      marker a chronic nephropathy or a thrombophilic disorder. The HELLP syndrome is a
      very demonstrative example of the help the internist can afford to the
      obstetrician in the management of pregnancy-associated disorders.

PMID- 18723257
TI  - Managing a work-life balance: the experiences of midwives working in a group
      practice setting.
AB  - OBJECTIVE: To explore how a group of midwives achieved a work-life balance
      working within a caseload model of care with flexible work hours and on-call
      work. DESIGN: in-depth interviews were conducted and the data were analysed using
      a data-driven thematic analysis technique. SETTING: Children, Youth and Women's
      Health Service (CYWHS) (previously Women's and Children's Hospital), Adelaide,
      where a midwifery service known as Midwifery Group Practice (MGP) offers a
      caseload model of care to women within a midwife-managed unit. PARTICIPANTS: 17
      midwives who were currently working, or had previously worked, in MGP. FINDINGS:
      analysis of the midwives' individual experiences provided insight into how
      midwives managed the flexible hours and on-call work to achieve a sustainable
      work-life balance within a caseload model of care. KEY CONCLUSIONS: it is
      important for midwives working in MGP to actively manage the flexibility of their
      role with time on call. Organisational, team and individual structure influenced
      how flexibility of hours was managed; however, a period of adjustment was
      required to achieve this balance. IMPLICATIONS: the study findings offer a
      description of effective, sustainable strategies to manage flexible hours and on
      call work that may assist other midwives working in a similar role or considering
      this type of work setting.

PMID- 18723258
TI  - Incorrect advice: the most significant negative determinant on breast feeding in
      Malta.
AB  - OBJECTIVE: this study reviewed breast-feeding rates in Malta for the first six
      months of life and identified reasons why mothers discontinue breast feeding in
      this small island state. DESIGN AND PARTICIPANTS: a random sample of 405 new
      mothers who chose to breast feed in the only major state hospital were contacted
      by phone one week postnatally and again each month up to six months, and
      presented with a questionnaire relating to their feeding experience. FINDINGS:
      breast-feeding attrition rates were high with just 152 (38%) of 403 analysable
      babies still breast feeding at six months. The reasons for stopping breast
      feeding were categorised by: maternal choice; medical reasons; lack of
      information; social reasons, incorrect advice and no reason provided. 200 (50%)
      of the total cohort stopped breast feeding following incorrect advice from health
      professionals. Just 14 (3.5%) and 17 (4.2%) mothers stopped as a result of their
      own choice or a medical problem, respectively. Of the total of 403, 77 (19%)
      mothers introduced supplementary bottle feeds in hospital; of these, 70 (91%)
      stopped breast feeding altogether soon afterwards. This compared with just 180
      (55%) of 326 women who did not introduce bottle feeds in hospital yet
      subsequently discontinued breast feeding (p<0.001). KEY CONCLUSIONS: many health
      professionals in Malta are not sufficiently committed to supporting breast
      feeding mothers, and artificial feeds are widely recommended without any
      scientific-based rationale. Incorrect advice on breast feeding is often given
      early prior to discharge from hospital. As a result, many Maltese mothers
      introduce supplementary artificial milk feeds in hospital, and this is
      significantly associated with subsequent cessation of breast feeding within six
      months of discharge. IMPLICATIONS FOR PRACTICE: the introduction of a clear
      hospital breast-feeding policy and appropriate education for all health
      professionals involved in maternity care is strongly recommended.

PMID- 18723259
TI  - Research and development on biomechanics in China.

PMID- 18723260
TI  - Self-referential processing of negative stimuli within the ventral anterior
      cingulate gyrus and right amygdala.
AB  - Neural activity associated with self-referential processing of emotional stimuli
      was investigated using whole brain functional magnetic resonance imaging (fMRI).
      Fifteen healthy subjects underwent fMRI scanning while making judgments about
      positive and negative trait words in four conditions (self-reference, other
      reference, semantic processing, and letter processing). Significant activity was
      observed in the right ventral anterior cingulate gyrus and the right amygdala in
      the negative-word/self-reference condition, and in the left amygdala in the
      positive-word/self-reference condition. Compared with the semantic-processing
      condition, the self-reference conditions showed significantly more activity in
      the medial prefrontal and temporal gyri, posterior cingulate gyrus, and
      precuneus. These results suggest that the medial prefrontal gyrus, posterior
      cingulate gyrus, and precuneus are associated with a self-referential processing,
      and the ventral anterior cingulate gyrus is involved in self-referential
      processing of negative emotional stimuli. The results also suggest that the
      amygdala is associated with self-referential processing of both positive and
      negative emotional stimuli.

PMID- 18723261
TI  - Enhanced divergent thinking and creativity in musicians: a behavioral and near
      infrared spectroscopy study.
AB  - Empirical studies of creativity have focused on the importance of divergent
      thinking, which supports generating novel solutions to loosely defined problems.
      The present study examined creativity and frontal cortical activity in an
      externally-validated group of creative individuals (trained musicians) and
      demographically matched control participants, using behavioral tasks and near
      infrared spectroscopy (NIRS). Experiment 1 examined convergent and divergent
      thinking with respect to intelligence and personality. Experiment 2 investigated
      frontal oxygenated and deoxygenated hemoglobin concentration changes during
      divergent thinking with NIRS. Results of Experiment 1 indicated enhanced
      creativity in musicians who also showed increased verbal ability and schizotypal
      personality but their enhanced divergent thinking remained robust after co
      varying out these two factors. In Experiment 2, NIRS showed greater bilateral
      frontal activity in musicians during divergent thinking compared with
      nonmusicians. Overall, these results suggest that creative individuals are
      characterized by enhanced divergent thinking, which is supported by increased
      frontal cortical activity.

PMID- 18723263
TI  - Targeting of heat-shock protein 32/heme oxygenase-1 in canine mastocytoma cells
      is associated with reduced growth and induction of apoptosis.
AB  - OBJECTIVE: Advanced mast cell (MC) neoplasms are usually resistant to
      conventional therapy. Therefore, current research focuses on new targets in
      neoplastic MC and development of respective targeted drugs. Mastocytomas in dogs
      often behave as aggressive tumors. We report that heat-shock protein 32 (Hsp32),
      also known as heme oxygenase-1, is a survival-enhancing molecule and new target
      in canine mastocytoma cells. MATERIALS AND METHODS: As assessed by reverse
      transcriptase polymerase chain reaction, Northern blotting, immunocytochemistry,
      and Western blotting, primary neoplastic dog MC, and the canine mastocytoma
      derived cell line C2 expressed Hsp32 mRNA and the Hsp32 protein in a constitutive
      manner. RESULTS: The KIT-targeting drug midostaurin inhibited expression of
      Hsp32, as well as survival in C2 cells. Confirming the functional role of Hsp32,
      the inhibitory effect of midostaurin on C2 cells was markedly reduced by the
      Hsp32-inductor hemin. Two pharmacologic Hsp32-inhibitors, styrene maleic-acid
      micelle-encapsulated ZnPP (SMA-ZnPP) and pegylated zinc-protoporphyrin (PEG-ZnPP)
      were applied. Both drugs were found to inhibit proliferation of C2 cells as well
      as growth of primary neoplastic canine MC. The growth-inhibitory effects of SMA
      ZnPP and PEG-ZnPP were dose- and time-dependent (IC(50): 1-10 muM) and found to
      be associated with induction of apoptosis. CONCLUSIONS: Hsp32 is an important
      survival factor and interesting new target in neoplastic canine MC. Trials with
      Hsp32-targeted drugs are now warranted to define the clinical efficacy of these
      drugs.

PMID- 18723265
TI  - IL-17F/IL-17R interaction stimulates granulopoiesis in mice.
AB  - OBJECTIVE: IL-17F, a member of the interleukin (IL)-17 cytokine family, most
      closely resembles IL-17A structurally. IL-17A is a potent stimulator of
      granulopoiesis; its expression is induced in response to microbial challenge.
      Although IL-17F is considered to be a weak IL-17A analog that is also mediating
      its effect via IL-17R, its exact role and in vivo functions are unknown. Our goal
      was to determine the in vivo activity of IL-17F on granulopoiesis as well as on
      release of granulopoiesis-stimulating downstream cytokines in mice and directly
      compare its effect to IL-17A. MATERIALS AND METHODS: Murine IL-17A (mIL-17A) or
      IL-17F (mIL-17F) was expressed in vivo in C57BL6 mice using adenoviral gene
      transfer technology. Peripheral cell counts were assessed as well as
      hematopoietic precursors using colony-forming assays at set time points.
      Downstream cytokines were measured using enzyme-linked immunosorbent assay and
      reverse transcriptase polymerase chain reaction. RESULTS: We found mIL-17F to
      have similar expression kinetics as mIL-17A in splenocytes in vitro and in vivo,
      following challenge with microbial agents. Overexpression of mIL-17F in vivo
      resulted in similar neutrophilia and only in slightly reduced myeloid progenitor
      expansion when compared to mIL-17A. In vivo, there was no difference in releases
      for granulocyte-macrophage colony-stimulating factor; regulated on activation,
      normal T expressed and secreted; interferon-inducible protein-10; IL-6; and
      monocyte chemotactic protein-1 between either cytokine. IL-1A, macrophage
      inflammatory protein -2 (MIP), KC, and granulocyte colony-stimulating factor
      expression was approximately half of that seen with mIL-17A. CONCLUSION: Both IL
      17A and IL-17F are induced by similar stimuli, have similar expression kinetics
      and despite only minimal in vitro activity for IL-17F, surprisingly they exert
      similar in vivo bioactivity. IL-17F bioactivity appears to be augmented in vivo
      through mechanisms that require further investigation.

PMID- 18723264
TI  - Phenotypic variability within the JAK2 V617F-positive MPD: roles of progenitor
      cell and neutrophil allele burdens.
AB  - OBJECTIVE: The myeloproliferative disorders (MPD), polycythemia vera (PV),
      essential thrombocytosis (ET), and primary myelofibrosis (PMF), differ
      phenotypically, but share the same JAK2(V617F) mutation. We examined the
      relationship of the quantitative JAK2(V617F) allele burden to MPD disease
      phenotype among the three MPD classes and within PV. MATERIALS AND METHODS: We
      measured the JAK2(V617F) allele percentage in genomic DNA from neutrophils,
      CD34(+) cells, and cloned progenitors in 212 JAK2(V617F)-positive MPD patients
      and correlated the allele burdens to both disease class and disease features.
      RESULTS: In ET and PV, mean CD34(+) cell JAK2(V617F) allele burdens were lower
      than the corresponding neutrophil allele burdens, but these were equivalent in
      PMF. JAK2(WT) progenitors were present in ET and PV when the CD34(+) JAK2(V617F)
      allele burden was lower than the neutrophil allele burden, but not in PV and PMF
      subjects in whom the CD34(+) cell and neutrophil allele burdens were similar.
      CD34(+) cell JAK2(V617F) clonal dominance, defined as coherence between the
      CD34(+) cell and neutrophil JAK2(V617F) allele burdens, was present in 24% of ET,
      56% of PV, and 93% of PMF patients, and was independent of the CD34(+) cell
      JAK2(V617F) genotype. Clonally dominant PV patients had significantly longer
      disease durations, higher white cell counts, and larger spleens than nondominant
      PV patients. CONCLUSIONS: We conclude that the extent of JAK2(V617F) CD34(+) cell
      clonal dominance is associated with disease phenotype within the MPD and, in PV,
      is associated with extramedullary disease, leukocytosis, and disease duration.

PMID- 18723267
TI  - Human-caused wildfire risk rating for prevention planning in Spain.
AB  - This paper identifies human factors associated with high forest fire risk in
      Spain and analyses the spatial distribution of fire occurrence in the country.
      The spatial units were 6,066 municipalities of the Spanish peninsular territory
      and Balearic Islands. The study covered a 13-year series of fire occurrence data.
      One hundred and eight variables were generated and input to a dedicated
      Geographic Information System (GIS) to model different factors related to fire
      ignition. After exploratory analysis, 29 were selected to build a predictive
      model of human fire ignition using logistic regression analysis. The binary model
      estimated the probability of high or low occurrence of forest fires, as defined
      by an ignition danger index that is currently used by the Spanish forest service
      (number of fires divided by forest area in each municipality). Thirteen
      explanatory variables were identified by the model. They were related to
      agricultural landscape fragmentation, agricultural abandonment and development
      processes. The prediction agreement found between the model binary outputs and
      the historical fire data was 85.3% for the model building dataset (60% of
      municipalities). A slightly lower predictive power (76.2%) was found for the
      validation data (the remaining 40%). The probabilistic output of the logistic was
      significantly related to the raw ignition index (Spearman correlation of 0.710)
      used by the Spanish Forest Service. Therefore, the model can be considered a good
      predictor of human-caused fire risk, aiding spatial decisions related to
      prevention planning in Spanish municipalities.

PMID- 18723266
TI  - Genetic profiling of myeloproliferative disorders by single-nucleotide
      polymorphism oligonucleotide microarray.
AB  - OBJECTIVE: Myeloproliferative disorders (MPD) are clonal hematopoietic diseases
      that include polycythemia vera (PV), essential thrombocytosis (ET), and primary
      myelofibrosis (PMF). Mutations in JAK2 are present in many MPD patients.
      Additional genomic abnormalities are not fully examined in MPD. MATERIALS AND
      METHODS: We used single-nucleotide polymorphism DNA microarray (SNP-chip) to
      analyze 43 patients with MPD (10 PV, 17 ET, and 16 PMF) for genomic aberrations.
      RESULTS: Genomic abnormalities were rare in ET. The region containing either RB
      (13q14) or NF1 (17q11) was deleted in 4 of the 16 PMF, especially PMF with no
      JAK2 mutations. All five cases of PV having homozygous JAK2V617F had loss of
      heterozygosity with normal copy number [uniparental disomy] involving the gene. A
      subpopulation with 9p uniparental disomy was detected in 11 MPD (3 PV, 1 ET, 7
      PMF). Uniparental disomy at 1p was found in one PV and three PMF. A novel
      mutation of MPL (Y591D), which was involved in this uniparental disomy, was found
      in 1 PV with JAK2 mutation. The other three cases of PMF with 1p uniparental
      disomy had point mutations of the MPL gene, either a novel mutation (S204F) or
      the previously described W515L. CONCLUSION: Genomic abnormalities, including 9p
      uniparental disomy/JAK2 point mutations, 1p uniparental disomy/MPL point
      mutations, deletions of RB1 and NF1 are common alterations in MPD, especially in
      PMF.

PMID- 18723268
TI  - Detrimental effects of 60 kHz sonothrombolysis in rats with middle cerebral
      artery occlusion.
AB  - Recent studies have raised concerns about the safety of low frequency ultrasound
      in transcranial therapeutic application in cerebral ischemia. This study was
      designed to evaluate safety aspects and potential deleterious effects of low
      frequency, 60 kHz ultrasound in treatment of experimental middle cerebral artery
      occlusion (MCAO) in rats. Forty-five male Wistar rats were submitted to either
      temporary (90 min; groups I and II) or permanent MCAO (groups III and IV) using
      the suture technique. All animals received recombinant tissue plasminogen
      activator (rt-PA) starting 90 min after the beginning of occlusion. Groups I and
      III were additionally treated with 60 kHz ultrasound (time average acoustic
      intensity 0.14 W/cm(2), duty cycle 50%). Outcome assessment consisted of magnetic
      resonance imaging (MRI) and clinical evaluation after 5 and 24 h, and histology
      (perfusion fixation after 24 h). Overall mortality was higher in animals treated
      with ultrasound (43% versus 29% in controls). Most animals died during the
      insonation period (25% in group I, 36% in group III, no animals in the
      corresponding control groups; p < 0.05). Histology revealed disseminated
      microscopic intracerebral bleeding and subarachnoid hemorrhage as one possible
      cause of death. After temporary occlusion, the hemispheric ischemic lesion volume
      was more than doubled in animals treated with ultrasound (20.3% +/- 14.1% versus
      8.6% +/- 5.1% in controls; p < 0.05). No difference in lesion volume was seen
      after permanent MCAO. Neurological assessment showed impairment of hearing as an
      additional specific side effect in ultrasound treated animals (65%, no impairment
      in controls). Although the results are not directly transferable to the human
      setting, this study clearly demonstrates the potential limitations of low
      frequency therapeutic ultrasound and the importance of pre-clinical safety
      assessment.

PMID- 18723269
TI  - Development of a thermal test object for the measurement of ultrasound
      intracavity transducer self-heating.
AB  - The elevated surface temperature of diagnostic ultrasound transducers imposes an
      important limitation to their safe use in clinical situations. Moreover,
      particular care should be taken if transvaginal transducers are to be used during
      routine scans in the first few weeks of pregnancy as the transducer surface can
      be very close to embryonic/fetal tissues. Published results have shown that the
      heating of tissue due to transducer self-heating can equal and often exceed the
      acoustic heating contribution. In this article, we report the development of a
      portable self contained thermal test object (TTO) capable of assessing the self
      heating of intracavity diagnostic ultrasound transducers. The thermal
      conductivity and volumetric heat capacity of the tissue mimicking material (TMM)
      used in the TTO were measured, yielding values of (0.56 +/- 0.01) W m(-1) K(-1)
      and (3.5 +/- 0.8) MJ m(-3) K(-1). The speed of sound of the TMM was measured as
      1540 m s(-1) and the attenuation over a frequency range of 2 to 10 MHz was found
      to be (0.50 +/- 0.01) dB cm(-1) MHz(-1). These results are in excellent agreement
      with the International Electrotechnical Commission (IEC 60601-2-37) requirements
      and the previously published properties of biological soft tissue. The
      temperature stability and uniformity, and suitability of the TTO for the
      measurement of transducer self-heating were tested and found to be satisfactory.
      The TTO reached a stable temperature of 37 degrees C in 3 h and the spatial
      variation in temperature was less than +/- 0.2 degrees C. Lastly, transducer self
      heating measurements from a transvaginal transducer exceeded the IEC temperature
      limit of 43 degrees C in less than 5 min and the temperature reached after 30 min
      was 47.3 degrees C.

PMID- 18723270
TI  - Measurements of ultrasonic backscattered spectral centroid shift from spine in
      vivo: methodology and preliminary results.
AB  - Ultrasonic backscatter measurements from vertebral bodies (L3 and L4) in nine
      women were performed using a clinical ultrasonic imaging system. Measurements
      were made through the abdomen. The location of a vertebra was identified from the
      bright specular reflection from the vertebral anterior surface. Backscattered
      signals were gated to isolate signal emanating from the cancellous interiors of
      vertebrae. The spectral centroid shift of the backscattered signal, which has
      previously been shown to correlate highly with bone mineral density (BMD) in
      human calcaneus in vitro, was measured. BMD was also measured in the nine
      subjects' vertebrae using a clinical bone densitometer. The correlation
      coefficient between centroid shift and BMD was r = -0.61. The slope of the linear
      fit was -160 kHz / (g/cm(2)). The negative slope was expected because the
      attenuation coefficient (and therefore magnitude of the centroid downshift) is
      known from previous studies to increase with BMD. The centroid shift may be a
      useful parameter for characterizing bone in vivo.

PMID- 18723271
TI  - Evaluation of targeting errors in ultrasound-assisted radiotherapy.
AB  - A method for validating the start-to-end accuracy of a 3-D ultrasound (US)-based
      patient positioning system for radiotherapy is described. A radiosensitive
      polymer gel is used to record the actual dose delivered to a rigid phantom after
      being positioned using 3-D US guidance. Comparison of the delivered dose with the
      treatment plan allows accuracy of the entire radiotherapy treatment process, from
      simulation to 3-D US guidance, and finally delivery of radiation, to be
      evaluated. The 3-D US patient positioning system has a number of features for
      achieving high accuracy and reducing operator dependence. These include using
      tracked 3-D US scans of the target anatomy acquired using a dedicated 3-D
      ultrasound probe during both the simulation and treatment sessions, automatic 3-D
      US-to-US registration and use of infrared LED (IRED) markers of the optical
      position-sensing system for registering simulation computed tomography to US
      data. The mean target localization accuracy of this system was 2.5 mm for four
      target locations inside the phantom, compared with 1.6 mm obtained using the
      conventional patient positioning method of laser alignment. Because the phantom
      is rigid, this represents the best possible set-up accuracy of the system. Thus,
      these results suggest that 3-D US-based target localization is practically
      feasible and potentially capable of increasing the accuracy of patient
      positioning for radiotherapy in sites where day-to-day organ shifts are greater
      than 1 mm in magnitude.

PMID- 18723272
TI  - Induction of apoptosis in sonoporation and ultrasonic gene transfer.
AB  - The role of apoptosis in sonoporation and ultrasound-enhanced gene transfection
      of cell suspensions was examined in vitro. Suspensions of HL-60 and of CHO-K1
      cells were exposed to 2.25-MHz continuous ultrasound for 1 min in a 60-rpm
      rotating-tube exposure system, with ultrasound contrast media added to ensure
      nucleation of cavitation. Cell necrosis was measured by trypan blue dye exclusion
      (using a hemacytometer) and by propidium iodide nuclear staining (using flow
      cytometry). Apoptosis was detected by the annexin V method with Alexa Fluor 350
      as the fluorescent label, and confirmed by Hoechst 33342 nuclear staining.
      Sonoporation cell loading was assessed by uptake of large fluorescent-dextran
      molecules from the medium. Transfection was demonstrated by expression of green
      fluorescent protein (GFP) from plasmids transferred into the cells by the
      treatment. Cell scoring was performed by flow cytometry, with necrotic cell
      events excluded. For HL-60 cells at 0.4 MPa, cell loading and transfection was
      significantly increased relative to shams at 2, 6 and 24 h post exposure, peaking
      at 19.0 +/- 5.5% and 9.6 +/- 4.2% of non-necrotic cells, respectively, at 6 h.
      However, about one third of the treatment-positive cells were identified as
      apoptotic. The cell loading and gene transfer effects increased for increasing
      peak rarefactional pressure amplitude, reaching 24.4 +/- 7.7% and 12.7 +/- 5.1%
      of non-necrotic cells, respectively, for 0.6-MPa exposure. However, the lethal
      cellular injury caused by cavitation in the rotating tube system reduced the
      overall apparent efficacy of cell loading and gene transfer to 5.1 +/- 2.1% and
      2.1 +/- 0.9%, respectively, after accounting for necrosis and apoptosis. Similar
      tests with CHO cells showed increased sonoporation but mostly cell death by
      necrosis, rather than apoptosis. The induction of apoptosis by cavitation
      treatments should be considered as a possible confounding factor, in addition to
      necrosis, in sonoporation and ultrasonic gene transfer research.

PMID- 18723274
TI  - A new TAG-72 cancer marker peptide identified by phage display.
AB  - Radiolabeled peptides as markers of cancer targets have demonstrated their value
      in diagnostic imaging and radiotherapy. The 16 mer f88-4/Cys6 phage display
      library was applied to affinity purified TAG-72 and three consensus peptides were
      identified: VHHSCTKLTHCCQNWH (A2-13), GGVSCMQTSPVCENNL (A2-6) and
      TKRDCSAQNYGCQKAI (A2-11). The A2-13 and A2-6 phages showed the highest percent
      binding to LS-174T cells by flow cytometry and were 3-fold higher than a control
      phage, while fluorescence microscopy showed that both A2-6 and A2-13 phages bound
      to the LS-174T cell membrane. However, only the A2-6 phage demonstrated
      specificity by low binding to the TAG-72 negative cell HT-29. Furthermore, the
      synthesized free A2-6 peptide demonstrated specific binding to LS-174T cells by
      flow cytometry and by immunohistochemical staining of xenograft tumor compared to
      normal colon. These data indicate that the A2-6 peptide is specific for the TAG
      72 cancer target.

PMID- 18723275
TI  - Silibinin inhibits cell growth and induces apoptosis by caspase activation, down
      regulating survivin and blocking EGFR-ERK activation in renal cell carcinoma.
AB  - Silibinin as an effective anti-cancer and chemopreventive agent in various
      epithelial cancer models has been reported inhibition of cancer cell growth
      through mitogenic signaling pathways. However, whether it could inhibit renal
      cell carcinoma growth and what are the underlying mechanisms is still not well
      elucidated. Since EGFR-MAPK and apoptosis pathways play important roles in renal
      cell carcinoma survival. Here, for the first time we evaluated the inhibitory
      proliferation effects of silibinin in renal cell carcinoma growth and examined
      whether silibinin modulates EGFR-MAPK and tumor apoptosis cascades signals. Our
      results indicated that silibinin effectively inhibits the renal cancer carcinoma
      Caki-1 cell proliferation and induces apoptosis through inhibiting the activation
      of EGFR and ERK and the expression of survivin, up-regulating the expression of
      p53 and triggering the cascades of caspase pathways. Our results suggested
      silibinin might be as one of the candidate chemopreventive agents for renal cell
      carcinoma therapy.

PMID- 18723276
TI  - A novel dynamic matrix detachment model reveals a shift from apoptosis to
      necrosis in melanoma cells.
AB  - Anchorage-independence is a hallmark of invasive cancer. The setback of the
      classical poly-HEMA static matrix detachment (SMD) anoikis model is the absence
      of dynamic fluid circulation, resulting in cell aggregates. We addressed this
      problem by developing a novel 3D cell culture dynamic matrix detachment (DMD)
      model with a turbulent-free laminar flow, yielding a very low shear stress. In
      this study, we focused on melanoma cells where apoptosis was evaluated both via
      annexin V flow cytometry and caspase cleavage. The DMD model was superior to SMD
      in the induction of melanoma cell death and in revealing a shift from apoptosis
      to necrotic cell death, as evident by failure to activate caspase 9 and a
      decrease in annexin V stain. Combination of DMD with cisplatin could further
      accentuate necrotic cell death in cisplatin-resistant melanoma cells. Thus, the
      DMD model may be a useful matrix deprivation model to identify necrotic vs.
      apoptotic cell death pathways.

PMID- 18723277
TI  - Adsorption characteristics of As(V) on iron-coated zeolite.
AB  - The sorption characteristics of arsenic(As(V)) on iron-coated zeolite (ICZ) were
      investigated through batch and column studies. As(V) was completely removed
      within 30 min in a concentration of 2mg/l, with a 100g/l dose of ICZ. Optimum
      dose of ICZ was 33.3g/l at a concentration of 20.12 mg/l and the effect of
      solution pH was negligible at a pH range of 3.0<pH<10.0. Langmuir Isotherm Model
      was suitable to explain the sorption characteristics of As(V) onto ICZ. The co
      presence of sulfate ions inhibited sorption of As(V) because of competitive
      adsorption. The adsorption capacity of ICZ for As(V) was 0.68 mg/g. Based on the
      result, ICZ is a suitable material to treat the mine drainage or wastewater
      bearing As(V).

PMID- 18723278
TI  - A material flow of lithium batteries in Taiwan.
AB  - Li batteries, including secondary and cylindrical/button primary Li batteries,
      are used worldwide in computers, communications and consumer electronics
      products. However, there are several dangerous issues that occur during the
      manufacture, shipping, and storage of Li batteries. This study analyzes the
      material flow of lithium batteries and their valuable heavy metals in Taiwan for
      the year 2006 by material flow analysis. According to data from the Taiwan
      Environmental Protection Administration, Taiwan External Trade Development
      Council, Bureau of Foreign Trade, Directorate General of Customs, and the Li
      batteries manufactures/importers/exporters. It was found that 2,952,696 kg of Li
      batteries was input into Taiwan for the year 2006, including 2,256,501 kg of
      imported Li batteries and 696,195 kg of stock Li batteries in 2005. In addition,
      1,113,867 and 572,215 kg of Li batteries was domestically produced and sold
      abroad, revealing that 3,494,348 kg of different types of Li batteries was sold
      in Taiwan. Of these domestically sold batteries, 504,663 and 146,557 kg were
      treated domestically and abroad. Thus, a total of 2,843,128 kg of Li batteries
      was stored by individual/industry users or illegally disposed. In addition, it
      was also observed that 2,120,682 kg of heavy metals contained in Li batteries,
      including Ni, Co, Al, Cu and Ni, was accumulated in Taiwan, with a recycled value
      of 38.8 million USD. These results suggest that these heavy metals should be
      recovered by suitable collection, recycling and reuse procedures.

PMID- 18723280
TI  - Defluoridation of water using magnesia/chitosan composite.
AB  - Magnesia (MgO) is a well-known adsorbent showing extremely high defluoridation
      capacity (DC). In order to over come the limitations of MgO for field
      applications, an attempt has been made to modify magnesia with abundant
      biomaterial chitosan to form magnesia/chitosan (MgOC) composite in a usable form
      and its merits over conventional magnesia and raw chitosan is established.
      Removal of fluoride from aqueous solution with MgO and MgOC composite was studied
      with batch equilibrium experiments. At equilibrium, MgOC composite has a DC of
      4440 mg F(-)/kg while for magnesia it is only 2175 mg F(-)/kg. The
      physicochemical properties of the synthesised MgOC composite were analyzed with
      FTIR and SEM with EDAX studies. The equilibrium data were fitted with isotherm
      and kinetic models. Thermodynamic parameters viz, Delta G degrees, Delta H
      degrees and DeltaS degrees were calculated to understand the nature of sorption.
      Field studies were carried out to find the suitability of these sorbents at field
      conditions.

PMID- 18723279
TI  - Characterization and treatability studies of tannery wastewater using chemically
      enhanced primary treatment (CEPT)--a case study of Saddiq Leather Works.
AB  - Chemically enhanced primary treatment (CEPT) is a technology that uses coagulants
      for enhanced pollutants removal at the primary stage of the wastewater treatment.
      This paper presents the detailed characteristics of tannery wastewater. It also
      explains effectiveness of CEPT in removing pollutants from tannery wastewater
      using various metal salts. The results of this study demonstrated that the
      tannery effluent had high concentrations of organic matter, solids, sulfates,
      sulfides and chromium. Alum, ferric chloride and ferric sulfate were tested as
      coagulants using jar test apparatus. Alum was found to be the suitable coagulant
      for tannery wastewater in a dose range of 200-240 mg/L as Al(2)(SO(4))(3). With
      alum, percentage removal efficiency for turbidity, total suspended solids (TSS),
      chemical oxygen demand (COD) and chromium was found to be 98.7-99.8, 94.3-97.1,
      53.3-60.9, and 98.9-99.7%, respectively. National effluent quality standards for
      total suspended solids and chromium were met after CEPT. However, COD content was
      high, emphasizing the need of secondary treatment for the tannery effluent.

PMID- 18723281
TI  - Adsorption kinetic of arsenates as water pollutant on iron, manganese and iron
      manganese-modified clinoptilolite-rich tuffs.
AB  - Arsenate adsorption from aqueous solutions onto clinoptilolite-heulandite rich
      tuffs modified with iron or manganese or a mixture of both iron and manganese in
      this work was investigated. A kinetic model was considered to describe the
      arsenates adsorption on each zeolitic material. The modified clinoptilolite
      heulandite rich tuffs were characterized by scanning electron microscopy and X
      ray diffraction analysis. The elemental composition and the specific surface area
      of the zeolitic material were also determined. The arsenate adsorption by the
      modified zeolites was carried on in a batch system considering a contact time
      from 5 min to 24h for the kinetic experimentation. The arsenic was detected by
      atomic absorption spectrometer using a hydride generator. The kinetics of the
      arsenate adsorption processes were described by the pseudo-second-order model and
      the obtained parameter k varies from 0.15 to 5.66 microg/gh. In general, the
      results suggested that the kinetic adsorption of arsenates on the modified
      clinoptilolite-rich tuffs depend of the metallic specie that modified the surface
      characteristics of the zeolitic material, the chemical nature of the metal as
      well as the association between different metallic chemical species in the
      zeolitic surface.

PMID- 18723282
TI  - The impact of toxicity of metals on the activity of ureolytic mixed culture
      during the precipitation of calcium.
AB  - In this article, the inhibitory impact of metals on substrate utilization and
      microbial carbonate precipitation (MCP) by ureolytic mixed cultures (UMC) was
      investigated with glucose and mineral medium under batch conditions. The IC(50)
      (toxicant concentration eliciting 50% inhibitory effect) values were determined
      from the BOD values of samples. Inhibition, expressed as the value of 50%
      inhibitory effect (IC(50)), was evaluated by the decrease in substrate removal
      using BOD tests. The effect of toxicity of metals on substrate degradation,
      IC(50) values, was found to increase in the following order:
      Cd(II)>Cu(II)>Pb(II)>Cr(VI)>Ni(II)>Zn(II). Nitrification a possible phenomenon in
      the biocatalytic process was observed in several samples and this inhibited the
      precipitation of soluble calcium. During the removal of calcium from industrial
      calcium-rich wastewater, toxicity of metal at higher metal concentrations and
      possibility of nitrification at higher sludge ages should be considered.

PMID- 18723283
TI  - Nitrate removal by Thiobacillus denitrificans immobilized on poly(vinyl alcohol)
      carriers.
AB  - Nitrate contamination is becoming a widespread environmental problem, and
      autotrophic denitrification with Thiobacillus denitrificans is a promising
      process considering efficiency, cost and maintenance. The denitrification
      efficiencies of T. denitrificans were compared in batch reactors between free
      cells and cells immobilized on polyvinyl alcohol (PVA) carriers made with thrice
      freezing/thawing and boric acid methods. The results indicated that the free cell
      reactor of T. denitrificans added with 10% (v/v) of PVA carrier made by thrice
      freezing/thawing (PVA-TFT) exhibited faster in S(2)O(3)(2-)-S consumption,
      SO(4)(2-) generation, and NO(3)(-)-N denitrification, with corresponding values
      being 165 mg (S(2)O(3)(2-)-S)/L.d, 491 mg (SO(4)(2-))/Ld, and 44 mg (NO(3)(-)
      N)/Ld, which were increased by 50%, 61%, and 57% respectively compared to the
      control reactor with only free cells. Inhibition of denitrification by
      accumulated SO(4)(2-) in PVA-TFT reactor appeared at the concentration of
      approximately 6000 mg (SO(4)(2-))/L, and 75% of NO(3)(-)-N removal efficiency was
      achieved after 12d operation under the condition of initial 700 mg/L NO(3)(-)-N
      concentration.

PMID- 18723284
TI  - Poly(ethylene glycol) enhanced dehydrochlorination of poly(vinyl chloride).
AB  - Poly(ethylene glycol) (PEG), an environment-friendly reaction medium, has been
      adopted to accelerate the dehydrochlorination of poly(vinyl chloride) (PVC).
      Experimental results demonstrated that at 210 degrees C for 1h the dechlorination
      degree was as high as 74.2% for PVC/PEG, while for PVC only 50.0%. Moreover, from
      thermogravimetric analysis, it was found that for PVC/PEG the decomposition of
      PVC corresponding to the dehydrochlorination stage shifted to lower temperatures
      compared with that of pure PVC, suggesting some interactions exist between PEG
      and PVC that caused the faster dehydrochlorination rate. In addition, during this
      process, no waste byproducts such as KCl have been produced, and satisfactory
      recyclability of PEG (10 cycles) has been obtained.

PMID- 18723285
TI  - Profound reduction of somatic and visceral pain in mice by intrathecal
      administration of the anti-migraine drug, sumatriptan.
AB  - Sumatriptan and the other triptan drugs target the serotonin receptor subtypes1B,
      1D, and 1F (5-HT(1B/D/F)), and are prescribed widely in the treatment of
      migraine. An anti-migraine action of triptans has been postulated at multiple
      targets, within the brain and at both the central and peripheral terminals of
      trigeminal "pain-sensory" fibers. However, as triptan receptors are also located
      on "pain-sensory" afferents throughout the body, it is surprising that triptans
      only reduce migraine pain in humans, and experimental cranial pain in animals.
      Here we tested the hypothesis that sumatriptan can indeed reduce non-cranial,
      somatic and visceral pain in behavioral models in mice. Because sumatriptan must
      cross the blood brain barrier to reach somatic afferent terminals in the spinal
      cord, we compared systemic to direct spinal (intrathecal) sumatriptan. Acute
      nociceptive thresholds were not altered by sumatriptan pre-treatment, regardless
      of route. However, in behavioral models of persistent inflammatory pain, we found
      a profound anti-hyperalgesic action of intrathecal, but not systemic,
      sumatriptan. By contrast, sumatriptan was completely ineffective in an
      experimental model of neuropathic pain. The pronounced activity of intrathecal
      sumatriptan against inflammatory pain in mice raises the possibility that there
      is a wider spectrum of therapeutic indications for triptans beyond headache.

PMID- 18723286
TI  - Effects of morphine on the experimental illusion of pain produced by a thermal
      grill.
AB  - We compared the effects of systemic morphine on normal (heat and cold) pain and
      paradoxical burning pain evoked by the simultaneous application of innocuous warm
      and cold stimuli to the skin. Twelve healthy volunteers participated in a
      randomised, double-blind, cross-over study to compare the effects of intravenous
      administration of morphine (0.025 or 0.1mg/kg) or placebo (saline). Stimuli were
      applied to the palm of the right hand with a thermode ("thermal grill") composed
      of six bars, whose temperatures were controlled by Peltier elements. For each
      session, we measured the heat and cold pain thresholds and then successively
      measured the intensity of: (i) paradoxical pain evoked by a combination of non
      noxious warm and cold stimuli; (ii) "normal" pain evoked by suprathreshold heat
      or cold stimuli; (iii) non-painful sensations evoked by warm or cold stimuli at
      temperatures used to produce paradoxical pain. Measurements were performed before
      20min after the administration of morphine or placebo and 5min after the
      administration of the morphine antagonist, naloxone. The administration of
      0.1mg/kg of morphine, but not 0.025mg/kg, induced a significant and naloxone
      reversible reduction of paradoxical pain intensity, which was directly correlated
      with the reduction of normal cold pain. No differences were observed for non
      painful thermal sensations. The paradoxical burning pain evoked by a thermal
      grill can be modified pharmacologically by analgesics and share some mechanisms
      with normal pain. This unique experimental "illusion of pain" may represent a new
      model to test analgesics in healthy volunteers.

PMID- 18723287
TI  - Long-term skin temperature measurements - a practical diagnostic tool in complex
      regional pain syndrome.
AB  - Despite the development of the IASP criteria, diagnosing complex regional pain
      syndrome (CRPS) remains a challenge because all symptoms vary interindividually,
      including the vascular abnormalities. Previous studies showed that skin
      temperature asymmetries between the affected and contralateral extremity around 2
      degrees C are useful for diagnosing CRPS. However, they were either assessed only
      at one single point in time or during specific investigations including
      controlled thermoregulatory modulation of sympathetic activity which limits their
      practicability. The present study evaluated long-term skin temperature changes
      under everyday circumstances in 22 patients with CRPS, 18 patients with limb pain
      of other origin and 23 healthy controls. The asymmetries in skin temperature and
      oscillation number (Q Oscill), the percentage of assessed time with a-synchron
      temperature changes on both body sides and the determination coefficient of the
      individual regression (r2 id) were compared between the groups. Patients with
      CRPS differed significantly from healthy controls in nearly all parameters. Minor
      differences between both patient groups were found regarding the percentage of
      assessed time with side difference >2 degrees C (DeltaT2). However, both patient
      groups differed significantly in parameters characterizing the skin temperature
      dynamics. A sum score (2 *Q Oscill +r2 id +DeltaT2) allowed diagnosing CRPS with
      a specificity of 67% vs. patients with other painful diseases and 79% vs. healthy
      controls (sensitivity: 73%, respectively, 94%) and reflected the severity of the
      dysfunction in CRPS better than the mean skin temperature side differences alone.
      The applied skin temperature analysis can be easily applied in the clinical
      settings and serves as a further facet in the difficult diagnosis of CRPS.

PMID- 18723288
TI  - Occurrence of antibodies to Neospora caninum and Toxoplasma gondii in dogs from
      Pernambuco, Northeast Brazil.
AB  - A serological survey was carried out to assess the occurrence of anti-Neospora
      caninum antibodies in dogs from the State of Pernambuco. A total of 625 serum
      samples of dogs (289 from Paulista, 168 from Amaraji and 168 from Garanhuns) were
      tested by an immunofluorescence antibody assay for the detection of anti-N.
      caninum antibodies. A total of 177 (28.3%; IC 95%, 24.9-32.1) samples were
      positive. The seropositivity rates found in Paulista, Amaraji and Garanhuns were
      26% (IC 95%, 21-31.4), 26.2% (IC 95%, 19.7-33.5) and 34.5% (IC 95%, 27.4-42.2),
      respectively. Of the 177 serum samples positive to anti-N. caninum antibodies,
      170 were additionally tested for the presence of anti-Toxoplasma gondii
      antibodies and out of these 57.6% (IC 95%, 49.8-65.2) were positive. The results
      indicate that dogs from Amaraji, Paulista and Garanhuns are exposed to both N.
      caninum and T. gondii infections. The presence of dogs infected by N. caninum in
      Pernambuco represents a potential risk factor for the occurrence of outbreaks of
      abortion in cattle and small ruminants in this state. This study is the largest
      serological survey on the presence of anti-N. caninum antibodies in dogs carried
      out in Brazil and reports for the first time the exposure to N. caninum and T.
      gondii in dogs from Pernambuco.

PMID- 18723289
TI  - Intestinal parasites in various animals at a zoo in Malaysia.
AB  - A survey was undertaken to investigate the prevalence of intestinal parasites
      from different groups of mammals housed in a zoological garden in Malaysia. A
      total of 197 faecal samples were collected randomly from various primates (99),
      hoofed mammals (70) and feline (28). It was discovered that 89.3% of feline,
      54.5% of primates and 45.7% of hoofed mammals were infected with intestinal
      parasites. Intestinal parasites found in primates were Balantidium coli (19.2%),
      Cryptosporidium spp. (14.1%), hookworm (10.1%), Trichuris spp. (5.1%), Ascaris
      (4.0%) and Blastocystis spp. (2.0%). For hoofed mammals, hookworm had the highest
      prevalence (34.3%) followed by Trichuris spp. and Cryptosporidium spp. (5.7%).
      Meanwhile, for feline, Toxocara cati was the most prevalent (64.3%), followed by
      Cryptosporidium spp. (14.3%), Spirometra spp. (7.1%), and hookworm (3.6%).
      Animals that were infected were all asymptomatic with low parasite load. Routine
      monitoring of the presence of parasites in animals kept in the zoo is imperative
      in assisting zoo management in the formulation and implementation of preventive
      and control measures against the spread of infectious parasitic diseases among
      animals within the zoo or to humans.

PMID- 18723290
TI  - A Bayesian evaluation of three diagnostic assays for the detection of Giardia
      duodenalis in symptomatic and asymptomatic dogs.
AB  - A Bayesian approach was used to evaluate three commonly used diagnostic assays
      for the detection of Giardia duodenalis in dogs: microscopical examination (ME),
      a commercial immunofluorescence assay (IFA: MerifluorGiardia test) and a
      commercial immunochromatographic assay (SNAP: Idexx SNAPGiardia test). These
      assays were evaluated for use in two different settings: in a cross-sectional
      epidemiological survey in household dogs and in a clinical survey, both conducted
      in the northern part of Belgium. A total of 272 faecal samples from household
      dogs and 141 faecal samples from clinically affected dogs were examined using
      these three diagnostic assays. The Bayesian analysis indicated that all tests
      were highly specific (specificity above 90%), and that the IFA is more sensitive
      than SNAP and ME, both in an epidemiological and in a clinical setting. For all
      three tests, the estimated sensitivity values were higher in the clinical
      compared to the epidemiological survey, whereas the specificity values were
      comparable in both studies. The results of the present study indicate that IFA is
      a highly specific and sensitive technique for the detection of G. duodenalis
      cysts, both for use in an epidemiological or clinical survey. The SNAP is a
      specific and fairly sensitive technique for the diagnosis of Giardia in
      clinically affected dogs. Overall, the ME was found to be a specific diagnostic
      technique, although lacking sensitivity.

PMID- 18723291
TI  - Hypothesis: upregulation of a muscle-specific isoform of insulin-like growth
      factor-1 (IGF-1) by spinal manipulation.
AB  - Spinal manipulation is a manual therapy approach commonly employed by
      chiropractors, osteopaths and manipulative physiotherapists in the treatment of
      back pain. It is characterised by a rapid high velocity, low amplitude thrust
      which commonly causes an audible 'pop' or 'cavitation' in the joint. Any
      beneficial effects are generally explained with reference to changes in vertebral
      joint movement. This paper looks at the process of spinal manipulation to see if
      there is reason to expect effects beyond simple changes in the biomechanics of
      the spine. It shows that during the process of spinal manipulation, rapid
      stretching of spinal muscles is inevitable. It goes on to review recent evidence
      that muscle stretch is a potent stimulus for the upregulation of a splice product
      of the insulin-like growth factor gene by the stretched muscle. Evidence that the
      product of this gene (mechano-growth factor; MGF) promotes muscle growth and
      repair (myotrophism) is presented, together with evidence that MGF promotes the
      growth and repair of neurones (neurotrophism). Against this background the
      hypothesis is proposed that one of the effects of spinal manipulation is to
      stretch spinal muscles which will upregulate MGF and result in local myotrophic
      and neurotrophic effects. This growth factor hypothesis represents a major
      departure from the biomechanical and biopsychosocial models currently used to
      explain the effects of spinal manipulation, and could provide the basis for
      further studies aimed at defining the molecular correlates of this type of manual
      therapy.

PMID- 18723292
TI  - Ejaculation as a treatment for nasal congestion in men is inconvenient,
      unreliable and potentially hazardous.

PMID- 18723293
TI  - Inhalation of hydrocarbon combustion products as a cause of dendriform pulmonary
      ossification.

PMID- 18723294
TI  - Malignant angiomyolipoma in the liver: a case report with pathological and
      molecular analysis.
AB  - Malignant angiomyolipoma (AML) of the liver is rare. We report a case of AML with
      malignant transformation and metastases. A 30-year-old man had developed giant
      hepatic masses. Microscopically, the periphery of the tumor showed components of
      classic hepatic AML, but the central region contained atypical epithelioid
      components with extremely pleomorphic and hyperchromatic nuclei with frequent
      mitotic figures. Immunohistochemical analysis revealed that the epithelioid cells
      were positive for HMB-45 and smooth muscle actin. Furthermore, the atypical
      epithelioid cells displayed P53 immunoreactivity and mutation at exon 7 for p53.
      The tumor showed a typical monoclonal pattern but no loss of heterozygosity or
      microsatellite instability. Markedly atypical epithelioid cells with vascular
      invasion, distant metastasis, and fatal outcome were interpreted as malignant
      characteristics of hepatic AML. It is suggested that large tumor size,
      pleomorphic nuclei with high proliferation activity, and P53 immunoreactivity may
      predict the existence of malignant transformation of hepatic AML.

PMID- 18723295
TI  - Adjuvant stereotactic radiosurgery after resection of intracranial
      hemangiopericytomas.
AB  - PURPOSE: To evaluate adjuvant stereotactic radiosurgery (SRS) in the management
      of recurrent or residual intracranial hemangiopericytomas (HPCs), we assessed
      tumor control, survival, and complications in patients who had undergone gamma
      knife SRS as part of multimodal therapy. METHODS AND MATERIALS: We
      retrospectively reviewed the records of consecutive 20 HPC patients who had
      undergone SRS for 29 tumors. The median patient age was 51.5 years (range, 8.9
      80.2). All patients had undergone previous surgical resection of their tumors. In
      addition, 12 patients underwent fractionated radiotherapy before SRS. Of the 20
      patients, 16 patients had low-grade HPCs (20 tumors) and 4 had high-grade
      anaplastic HPCs (9 tumors). The median radiosurgery target volume was 4.5 cm(3)
      (range, 0.07-34.3), and the median marginal dose was 15.0 Gy (range, 10-20).
      RESULTS: At an average of 48.2 months (range, 7.2-124.1), 5 patients had died of
      metastases and 3 patients had died of disease progression. The overall survival
      after radiosurgery was 100%, 85.9%, and 13.8% at 1, 5, and 10 years,
      respectively. The follow-up imaging studies demonstrated tumor control in 21
      (72.4%) of 29 tumors. The progression-free survival rate after SRS at 1, 3, and 5
      years was 89.1% for low-grade HPCs and 88.9%, 66.7%, and 0%, respectively, for
      high-grade HPCs. The factors associated with improved progression-free survival
      included lower grade and higher marginal dose. Eight patients had intracranial or
      extracranial metastasis after the initial diagnosis, which correlated with the
      shorter survival. CONCLUSION: The results of our study have shown that adjuvant
      SRS after tumor resection is an important management option for patients with
      residual or recurrent HPCs and is particularly effective for less-aggressive
      tumors.

PMID- 18723296
TI  - Major late toxicities after conformal radiotherapy for nasopharyngeal carcinoma
      patient- and treatment-related risk factors.
AB  - PURPOSE: To retrospectively analyze the factors affecting late toxicity for
      nasopharyngeal carcinoma. METHODS AND MATERIALS: Between 1998 and 2003, 422
      patients were treated with a conformal technique with 2-Gy daily fractions to a
      total dose of 70 Gy. Conventional fractionation (5 fractions weekly) was used in
      232 patients and accelerated fractionation (6 fractions weekly) in 190 patients.
      One hundred seventy-one patients were treated with the basic radiotherapy course
      alone (Group 1), 55 patients had an additional boost of 5 Gy in 2 fractions
      (Group 2), and 196 patients underwent concurrent cisplatin-based chemotherapy
      (Group 3). RESULTS: The 5-year overall toxicity rate was significantly greater in
      Group 3 than in Group 1 (37% vs. 27%, p = 0.009). Although the overall rate in
      Group 2 was not elevated (28% vs. 27%, p = 0.697), a significant increase in
      temporal lobe necrosis was observed (4.8% vs. 0%, p = 0.015). Multivariate
      analyses showed that age and concurrent chemotherapy were significant factors.
      The hazard ratio of overall toxicity attributed to chemotherapy was 1.99 (95%
      confidence interval, 1.32-2.99, p = 0.001). The mean radiation dose to the
      cochlea was another significant factor affecting deafness, with a hazard ratio of
      1.03 (95% confidence interval, 1.01-1.05, p = 0.005) per 1-Gy increase. The
      cochlea that received >50 Gy had a significantly greater deaf rate (Group 1, 18%
      vs. 7%; and Group 3, 22% vs. 14%). CONCLUSION: The therapeutic margin for
      nasopharyngeal carcinoma is extremely narrow, and a significant increase in brain
      necrosis could result from dose escalation. The significant factors affecting the
      risk of deafness included age, concurrent chemoradiotherapy, and greater
      radiation dose to the cochlea.

PMID- 18723298
TI  - [Alternative techniques of fetal assessment during labor: future or past?].

PMID- 18723297
TI  - Phase I three-dimensional conformal radiation dose escalation study in newly
      diagnosed glioblastoma: Radiation Therapy Oncology Group Trial 98-03.
AB  - PURPOSE: To evaluate in a Phase I trial the feasibility and toxicity of dose
      escalated three-dimensional conformal radiotherapy (3D-CRT) concurrent with
      chemotherapy in patients with primary supratentorial glioblastoma (GBM). METHODS
      AND MATERIALS: A total of 209 patients were enrolled. All received 46 Gy in 2-Gy
      fractions to the first planning target volume (PTV(1)), defined as the gross
      tumor volume (GTV) plus 1.8 cm. A subsequent boost was given to PTV(2), defined
      as GTV plus 0.3 cm. Patients were stratified into two groups (Group 1: PTV(2) <75
      cm(3); Group 2: PTV(2) >or=75 cm(3)). Four RT dose levels were evaluated: 66, 72,
      78, and 84 Gy. Carmustine 80 mg/m(2) was given during RT, then every 8 weeks for
      6 cycles. Pretreatment characteristics were well balanced. RESULTS: Acute and
      late Grade 3/4 RT-related toxicities were no more frequent at higher RT dose or
      with larger tumors. There were no dose-limiting toxicities (acute Grade >or=3
      irreversible central nervous system toxicities) observed on any dose level in
      either group. On the basis of the absence of dose-limiting toxicities, dose was
      escalated to 84 Gy in both groups. Late RT necrosis was noted at 66 Gy (1
      patient), 72 Gy (2 patients), 78 Gy (2 patients), and 84 Gy (3 patients) in Group
      1. In Group 2, late RT necrosis was noted at 78 Gy (1 patient) and 84 Gy (2
      patients). Median time to RT necrosis was 8.8 months (range, 5.1-12.5 months).
      Median survival in Group 1 was 11.6-19.3 months. Median survival in Group 2 was
      8.2-13.9 months. CONCLUSIONS: Our study shows the feasibility of delivering
      higher than standard (60 Gy) RT dose with concurrent chemotherapy for primary
      GBM, with an acceptable risk of late central nervous system toxicity.

PMID- 18723299
TI  - [The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: clinical description and
      genetics].
AB  - The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by congenital
      aplasia of the uterus and the upper part (two-third) of the vagina. It may be
      isolated (type I) or associated with other malformations (type II or MURCS
      association). These latter involve the upper urinary tract, the skeleton and, to
      a lesser extent, the otologic sphere or the heart. The incidence of MRKH syndrome
      has been estimated as 1 in 4500 women. The prime feature is a primary amenorrhea
      in women presenting otherwise with normal development of secondary sexual
      characteristics and normal external genitalia. However, the vagina is reduced to
      a vaginal dimple with variable depth. The ovaries are normal and functional as
      well as the endocrine status. Karyotype is 46,XX, with no visible chromosome
      modification. The phenotypic manifestations of MRKH syndrome overlap with various
      other syndromes or malformations and thus require accurate delineation as well as
      differential diagnosis. For a long time, the syndrome has been considered as a
      sporadic anomaly, but increasing familial cases now support the hypothesis of a
      genetic cause currently under investigation. The syndrome appears to be
      transmitted as an autosomal dominant trait with incomplete penetrance and
      variable expressivity.

PMID- 18723300
TI  - Distribution of integrons and SGI1 among antibiotic-resistant Salmonella enterica
      isolates of animal origin.
AB  - In Salmonella enterica, resistance to antibiotics can be caused by the presence
      of SGI1, transposons or conjugative plasmids. In this study we were interested in
      the relative contribution of these genetic elements to the antibiotic resistance
      of S. enterica isolates collected within a single year in the Czech Republic from
      animal sources. Altogether 123 antibiotic-resistant isolates belonging to 16
      different S. enterica serovars were classified into 3 groups according to the
      presence of SGI1 and the presence of integrons. The first group consisted of 62
      strains in which neither SGI1 nor class 1 integron was detected. A high diversity
      among serovars and resistance phenotypes was found in this group. The second
      group consisted of 56 strains positive for both the SGI1 and class 1 integron,
      out of which 55 belonged to serovar Typhimurium and one to a nonmotile serovar
      [4,12] which harboured the SGI1-B variant. The third group comprised five strains
      which were positive for class 1 integron but negative for the SGI1. Sequencing of
      the integrons in these isolates identified integron with sat1 and aadA1 gene
      cassettes in S. Sandiego and S. Pullorum, dfrA1 and aadA1 gene cassettes in S.
      Typhimurium integron, and aadA21 gene cassette in S. Braenderub and S. Zanzibar.

PMID- 18723301
TI  - Prenatal depression restricts fetal growth.
AB  - OBJECTIVE: To identify whether prenatal depression is a risk factor for fetal
      growth restriction. METHODS: Midgestation (18-20 weeks GA) estimated fetal weight
      and urine cortisol and birthweight and gestational age at birth data were
      collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal
      weight and birthweight data were then used to compute fetal growth rates.
      RESULTS: Depressed women had a 13% greater incidence of premature delivery (Odds
      ratio (OR)=2.61) and 15% greater incidence of low birthweight (OR=4.75) than non
      depressed women. Depressed women also had elevated prenatal cortisol levels
      (p=.006) and fetuses who were smaller (p=.001) and who showed slower fetal growth
      rates (p=.011) and lower birthweights (p=.008). Mediation analyses further
      revealed that prenatal maternal cortisol levels were a potential mediator for the
      relationship between maternal symptoms of depression and both gestational age at
      birth and the rate of fetal growth. After controlling for maternal demographic
      variables, prenatal maternal cortisol levels were associated with 30% of the
      variance in gestational age at birth and 14% of the variance in the rate of fetal
      growth. CONCLUSION: Prenatal depression was associated with adverse perinatal
      outcomes, including premature delivery and slower fetal growth rates. Prenatal
      maternal cortisol levels appear to play a role in mediating these outcomes.

PMID- 18723302
TI  - Merosin-deficient congenital muscular dystrophy in Korea.
AB  - Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous
      group of muscle disorders, presenting at birth or early infancy with hypotonia,
      muscle weakness, joint contractures, and dystrophic changes in the muscles.
      Merosin-deficient CMD (MDCMD) is rare in Asian populations, but more common in
      Caucasians, comprising about 50% of CMDs. We report, for the first time in Korea,
      eight patients with merosin-deficient CMD, confirmed by immunohistochemical
      staining of muscle or skin samples. We also describe their wide spectrum of
      clinical features and neuroimaging findings. Among 35 patients diagnosed as CMD,
      almost 23% of them were proved to have MDCMD with typical phenotypic
      presentation. We infer that prevalence of MDCMD in Korea may not be as low as
      expected. One of the patients was diagnosed by skin biopsy, which is good
      alternative for diagnosis of MDCMD.

PMID- 18723303
TI  - Predicting executive function task scores with the Rey-Osterrieth Complex Figure.
AB  - The Boston Qualitative Scoring System (BQSS) is one of the scoring methods of the
      Rey-Osterrieth Complex Figure Test (ROCF). With BQSS, 17 qualitative ratings are
      generated, and subsequently 6 summary scores are calculated by combining several
      qualitative scores. Previously we showed that 5 of 6 BQSS summary scores were
      correlated with the scores of the several executive function tests in children.
      The objective of this study was to develop a new summary score which correlates
      with the executive function test scores more strongly than the existing summary
      scores. For this purpose, we conducted multiple regression analysis to predict
      PEN, CA, DSM of the Wisconsin Card Sorting Test Keio Version, and the Mazes
      scores from WISC-III, by the BQSS qualitative scores derived from ROCF drawings
      in copy condition. The subjects were 78 children with various neuropsychological
      disorders (5 years 5 months-14 years 11 months; mean: 9 years 2 months; F 22, M
      56). Significant predictive models were generated for PEN, CA, and Mazes scores.
      Among them the models for the Mazes scores were the most accurate. The second
      model for the Mazes scores was most suitable for a new summary score. Its degree
      of-freedom-adjusted coefficient of multiple determination and multiple
      correlation coefficient reached 0.467 and 0.695, respectively. A new summary
      score should be applied in future studies to evaluate its clinical usefulness.

PMID- 18723304
TI  - [Vaccinations of HIV-infected travelers].
AB  - Human immunodeficiency virus (HIV) positive international travelers are at higher
      risk of infectious complications. The pretravel assessment often provides an
      opportunity to update routine vaccinations and HIV patient specific vaccinations
      including pneumococcus, hepatitis A, hepatitis B, and influenza. Other
      vaccinations may be required or recommended. Decision for vaccination require
      considering the risk and severity of the vaccine, preventable diseases in the
      destination area, the nature of the vaccine (live attenuated vaccines or not),
      the patient's immune status, and the risk of virological rebound as a consequence
      of vaccination. The immunogenicity of vaccines is decreased in HIV patient with
      low CD4 cell counts (above 500 cells per cubic millimetres and particularly above
      200 cells per cubic millimetres) and in patients with a persistent HIV RNA viral
      load. Vaccines should be administered to patients whose HIV infections are in the
      early stage or in patients receiving HAART with a satisfactory immune status and
      reduced HIV RNA level. Testing of postvaccination antibodies is useful if
      serological protective levels are defined. In case of non-response after
      vaccination, few studies suggest that additional revaccination, increase of
      vaccine dose, intradermic vaccination, or use of prime-boost combination may be
      successful. Further research is needed to define vaccination strategies, adapted
      to the immune status of the HIV patient.

PMID- 18723305
TI  - Interdisciplinary consensus on the uses and technique of MR-guided vacuum
      assisted breast biopsy (VAB): results of a European consensus meeting.
AB  - PURPOSE: Quality assurance of MR-guided vacuum-assisted breast biopsy (VAB).
      METHOD: A consensus was achieved based on the existing literature and experience
      of an interdisciplinary group comprising European specialists in breast imaging
      and VAB. RESULTS: Full imaging work-up must be completed according to existing
      standards before an indication for MR-guided VAB is established. The procedure
      should be reserved for lesions demonstrable by MRI alone. Acquisition of >24
      cores (11-Gauge) should be routinely attempted, with the intention of
      sufficiently removing small lesions for accurate diagnosis. Following biopsy the
      patient should be re-imaged to demonstrate the biopsy site and its proximity to
      the lesion and hence the likely accuracy of the sampling. All patients should be
      discussed in a regular interdisciplinary conference and a documented consensus
      reached regarding patient management. Regular audit and review of all MR-guided
      VAB results and subsequent follow-up are recommended. CONCLUSION: This consensus
      includes protocols for the indication, performance parameters, interdisciplinary
      interpretation therapeutic recommendation, documentation and follow-up of MR
      guided VAB. It does not replace official recommendations for percutaneous biopsy.

PMID- 18723306
TI  - Developing an 'interactive' booklet on respiratory tract infections in children
      for use in primary care consultations.
AB  - OBJECTIVE: To construct a systematic process for developing an 'interactive'
      booklet for use in primary care consultations and to use this process to develop
      a booklet on respiratory tract infections in children. METHODS: Booklet
      development occurred through a number of stages, which included: expert group
      brainstorming and literature review, professional graphic design, readability
      assessment, and consultation with users. Consultation was achieved through the
      use of focus groups and interviews with parents, focus groups and independent
      booklet review by general practitioners, and booklet review and feedback by
      paediatricians. RESULTS: All development stages led to meaningful enhancements to
      the booklet. Consultation with parents demonstrated a desire for more information
      than anticipated, with a particular emphasis on the interpretation of signs and
      symptoms, and the recognition of serious illness. General practitioners
      contributed to the design and clarity of the booklet and helped to ensure that it
      would be acceptable for use within consultations. CONCLUSION: Written material
      needs to be developed in a systematic way and include consultation with the
      intended users. Focus groups are a valuable tool for consulting with consumers
      and practitioners in this regard. PRACTICE IMPLICATIONS: The process described
      can be used as a guide for those wishing to develop similar written materials.

PMID- 18723307
TI  - Patient-provider communication and cancer screening among unmarried women.
AB  - OBJECTIVES: Unmarried women are less likely than married women to receive
      recommended cancer screenings. Patient-provider communication is a consistent
      predictor of cancer screening among women. The purpose of this study was to
      investigate the relationship between patient and provider communication, barriers
      to cancer screening, and on-schedule breast and cervical cancer screening (BCCS)
      among unmarried women. METHODS: Data were from the Cancer Screening Project for
      Women, a 2003-2005 survey examining cancer screening practices. We computed
      polytomous logistic regression models to examine the relationship between
      communication (communication about tests, communication about sexual and intimate
      relationships), barriers to screening, and on-schedule BCCS among unmarried
      women. RESULTS: A total of 630 women were enrolled, and 605 women completed the
      baseline questionnaire. Overall, more than 60% reported on-schedule BCCS. More
      than half reported that their providers communicated about BCCS most or all of
      the time. Fewer than half communicated about sexual history and intimate
      relationships. Women who reported that their providers communicated about
      screening tests and their sexual and intimate relationships were more likely to
      be on-schedule for BCCS. CONCLUSION: Patient-provider communication about
      multiple topics may encourage women to remain on-schedule for their recommended
      cancer screenings. Longitudinal research should be conducted to examine whether
      communication predicts BCCS, and to examine how patient and provider
      characteristics may influence communication in order to promote adherence to
      screening guidelines for unmarried women. PRACTICE IMPLICATIONS: Comprehensive
      communication that goes beyond information about screening tests may impact
      adherence to cancer screening guidelines.

PMID- 18723308
TI  - Strategies to improve spinal cord ischemia in endovascular thoracic aortic
      repair: Outcomes of a prospective cerebrospinal fluid drainage protocol.
AB  - PURPOSE: Although endovascular repair of thoracic aortic aneurysm has been shown
      to reduce the morbidity and mortality rates, spinal cord ischemia remains a
      persistent problem. We evaluated our experience with spinal cord protective
      measures using a standardized cerebrospinal fluid (CSF) drainage protocol in
      patients undergoing endovascular thoracic aortic repair. METHODS: From 2004 to
      2006, 121 patients underwent elective (n = 52, 43%) and emergent (n = 69, 57%)
      endovascular thoracic aortic stent graft placement for thoracic aortic aneurysm
      (TAA) (n = 94, 78%), symptomatic penetrating ulceration (n = 11, 9%),
      pseudoaneurysms (n = 5, 4%) and traumatic aortic transactions (n = 11, 9%). In
      2005, routine use of a CSF drainage protocol was established to minimize the
      risks of spinal cord ischemia. The CSF was actively drained to maintain pressures
      <15 mm Hg and the mean arterial blood pressures were maintained at >/=90 mm Hg.
      Data was prospectively collected in our vascular registry for elective and
      emergent endovascular thoracic aortic repair and the patients were divided into 2
      groups (+CSF drainage protocol, -CSF drainage protocol). A chi(2) statistical
      analysis was performed and significance was assumed for P < .05. RESULTS: Of the
      121 patients with thoracic stent graft placement, the mean age was 72 years, 62
      (51%) were male, and 56 (46%) underwent preoperative placement of a CSF drain,
      while 65 (54%) did not. Both groups had similar comorbidities of coronary artery
      disease (24 [43%] vs 27 [41%]), hypertension (44 [79%] vs 50 [77%]), chronic
      obstructive pulmonary disease (18 [32%] vs 22 [34%]), and chronic renal
      insufficiency (10 [17%] vs 12 [18%]). None of the patients with CSF drainage
      developed spinal cord ischemia (SCI), and 5 (8%) of the patients without CSF
      drainage developed SCI within 24 hours of endovascular repair (P< .05). All
      patients with clinical symptoms of SCI had CSF drain placement and augmentation
      of systemic blood pressures to >/=90 mm Hg, and 60% (3 of 5 patients)
      demonstrated marked clinical improvement. CONCLUSION: Perioperative CSF drainage
      with augmentation of systemic blood pressures may have a beneficial role in
      reducing the risk of paraplegia in patients undergoing endovascular thoracic
      aortic stent graft placement. However, selective CSF drainage may offer the same
      benefit as mandatory drainage.

PMID- 18723309
TI  - Occam's razor: Intervene early to prevent more strokes!
AB  - The early risk of stroke after a patient suffers a transient ischemic attack
      (TIA)/minor stroke is significantly higher than previously thought. In most
      health systems, this (unfortunately) means that many vulnerable patients will
      have suffered their stroke before having had any chance of being considered for
      carotid endarterectomy (CEA) or carotid angioplasty with stenting (CAS). The
      problem is then compounded by institutional delays in finally undertaking
      CEA/CAS, which leads to even greater diminishing benefit to the patient.
      Notwithstanding the fact that the international trials used a 6-month threshold
      for inclusion, it remains an unpalatable fact that if CEA/CAS is delayed beyond
      12 weeks in symptomatic patients with North American Symptomatic Carotid
      Endarterectomy Trial (NASCET) 50% to 99% stenoses, the patient is exposed to all
      of the risks of intervening, but gains little in the way of long-term stroke
      prevention. The take-home message is, therefore, very simple; "intervene early to
      prevent more strokes". Occam's razor has never been sharper!

PMID- 18723310
TI  - An endogenously deposited fibrin scaffold determines construct size in the
      surgically created arteriovenous loop chamber model of tissue engineering.
AB  - BACKGROUND: An arteriovenous loop (AVL) enclosed in a polycarbonate chamber in
      vivo, produces a fibrin exudate which acts as a provisional matrix for the
      development of a tissue engineered microcirculatory network. OBJECTIVES: By
      administering enoxaparin sodium - an inhibitor of fibrin polymerization, the
      significance of fibrin scaffold formation on AVL construct size (including the
      AVL, fibrin scaffold, and new tissue growth into the fibrin), growth, and
      vascularization were assessed and compared to controls. METHODS: In Sprague
      Dawley rats, an AVL was created on femoral vessels and inserted into a
      polycarbonate chamber in the groin in 3 control groups (Series I) and 3
      experimental groups (Series II). Two hours before surgery and 6 hours post
      surgery, saline (Series I) or enoxaparin sodium (0.6 mg/kg, Series II) was
      administered intra-peritoneally. Thereafter, the rats were injected daily with
      saline (Series I) or enoxaparin sodium (1.5 mg/kg, Series II) until construct
      retrieval at 3, 10, or 21 days. The retrieved constructs underwent weight and
      volume measurements, and morphologic/morphometric analysis of new tissue
      components. RESULTS: Enoxaparin sodium treatment resulted in the development of
      smaller AVL constructs at 3, 10, and 21 days. Construct weight and volume were
      significantly reduced at 10 days (control weight 0.337 +/- 0.016 g [Mean +/- SEM]
      vs treated 0.228 +/- 0.048, [P < .001]: control volume 0.317 +/- 0.015 mL vs
      treated 0.184 +/- 0.039 mL [P < .01]) and 21 days (control weight 0.306 +/- 0.053
      g vs treated 0.198 +/- 0.043 g [P < .01]: control volume 0.285 +/- 0.047 mL vs
      treated 0.148 +/- 0.041 mL, [P < .01]). Angiogenesis was delayed in the
      enoxaparin sodium-treated constructs with the absolute vascular volume
      significantly decreased at 10 days (control vascular volume 0.029 +/- 0.03 mL vs
      treated 0.012 +/- 0.002 mL [P < .05]). CONCLUSION: In this in vivo tissue
      engineering model, endogenous, extra-vascularly deposited fibrin volume
      determines construct size and vascular growth in the first 3 weeks and is,
      therefore, critical to full construct development.

PMID- 18723311
TI  - Endovascular treatment for carotid artery stenosis after neck irradiation.
AB  - BACKGROUND: To lower the risk of complications, carotid angioplasty and stenting
      (CAS) has been proposed as an alternative to open surgery for carotid artery
      stenosis after neck irradiation. However, there are little postoperative data to
      support the benefits of this strategy. This study evaluated the outcome of CAS in
      patients who had undergone neck irradiation. METHODS: This retrospective study
      was conducted at 15 vascular surgery or interventional radiology centers in
      France between January 1998 and July 2006. A total of 135 patients (115 men) with
      a mean age of 67 +/- 8 years (range, 43-88) underwent CAS for 149 irradiation
      induced lesions. The interval between irradiation and discovery of the lesions
      was 12 +/- 8 years. Mean diameter reduction was 81% (range, 50%-95%), and
      stenosis was symptomatic in 34%. Contralateral carotid lesions were observed in
      48% of patients, including thrombosis in 18 and stenosis >50% in 53. RESULTS:
      Technical failure occurred during CAS in three cases. The overall technical
      success rate was 98%. A cerebral protection device was used in 59%. No death, one
      transient ischemic attack, and two strokes occurred during the first
      postoperative month. Mean follow-up was 30 months. Six patients were lost to
      follow-up. Survival rates were 93.9% at 1 year and 75.3% at 3 years.
      Complications after the first postoperative month included neurologic events in
      six, carotid thrombosis in nine, and restenosis in 18. The rates of freedom from
      neurologic and anatomic events were, respectively, 96.2% and 93.2% at 1 year and
      93.1% and 85.9% at 3 years. CONCLUSION: The immediate outcome of CAS for
      irradiation-induced carotid artery stenosis was satisfactory. Medium-term
      neurologic outcome was acceptable, but the incidence of anatomic events such as
      thrombosis and restenosis was high. A randomized study is needed to confirm that
      the outcome of the endovascular and surgical therapy is comparable in this
      indication.

PMID- 18723312
TI  - The role of sentinel node biopsy in ductal carcinoma in situ of the breast.
AB  - AIM: Sentinel node biopsy (SNB) is an accepted alternative to lymphadenectomy in
      the case of invasive breast carcinoma, although the sentinel node's role in
      ductal carcinoma in situ (DCIS) diagnosed on core needle biopsy has not been well
      defined nevertheless guidelines recommend this procedure. The purpose of this
      study was to determine the diagnostic value of sentinel nodes in female patients
      with primary DCIS using core needle stereotactic biopsy. MATERIAL AND METHODS:
      Between the years 2000 and 2005, 261 patients were diagnosed with DCIS by core
      needle biopsy. In this group, 183 patients underwent SNB to determine lymph node
      involvement. Those patients with metastases to the sentinel node underwent
      axillary lymphadenectomy. RESULTS: In the group of 183 patients that underwent
      SNB, 10 patients (5.5%) showed metastases to the sentinel lymph node.
      Histopathological studies of the primary lesions of these 10 patients revealed
      invasive ductal carcinoma in 6 cases (3.5%) and 1 case (0.5%) of invasive lobular
      carcinoma. Only 3 of the patients (1.5%) were given a final diagnosis of DCIS
      with metastases to sentinel lymph nodes, of which 2 cases were DCIS and 1 case
      was DCIS with microinvasion. Axillary lymphadenectomy performed on patients with
      abnormal SNB showed involvement of other axillary lymph nodes in 4 patients.
      CONCLUSIONS: SNB as a diagnostic tool in DCIS remains controversial as the number
      of cases of axillary lymph node metastases is minuscule. The biggest clinical
      challenge in this situation is a group of patients with primary diagnosis of DCIS
      in which invasive components are seen by mammotomic biopsy.

PMID- 18723313
TI  - Disrupted sleep the night before breast surgery is associated with increased
      postoperative pain.
AB  - Despite the best available clinical care, pain after surgery is a virtually
      universal patient experience that can have pervasive negative consequences. Given
      the large variability among patients in postoperative pain levels, research on
      novel modifiable risk factors is needed. One such factor suggested by recent
      experimental studies indicates that disruption of even a single night's sleep can
      increase subsequent pain in healthy volunteers. In this preliminary clinical
      study, we tested the hypothesis that poor sleep the night before surgery would
      predict heightened postoperative pain. Patients (n=24) scheduled for routine
      breast-conserving surgical procedures for the diagnosis or treatment of cancer
      were recruited and wore an actigraphy device providing objective, validated
      measures of sleep duration and disruption (low sleep efficiency). Pain severity
      and interference with daily activities for the week after surgery was assessed
      with the Brief Pain Inventory. As hypothesized, multiple regression analyses
      revealed that lower sleep efficiency was a significant predictor of greater pain
      severity and interference, controlling for age, race, and perioperative
      analgesics as appropriate. Sleep efficiency was not significantly related to
      measures of depressed mood, emotional upset, or relaxation assessed on the
      morning of surgery. Patients with sleep efficiency in the lowest tertile had
      clinically higher levels of pain (>2 points) compared with patients in the
      highest sleep efficiency tertile. Sleep duration had no significant effects. This
      preliminary clinical study supports the possibility that sleep disruption on the
      night before surgery may increase patients' experience of pain after surgery.
      Research to investigate the mechanisms underlying these effects and to explore
      the possible clinical benefits of interventions to improve patients' sleep before
      surgery is now warranted.

PMID- 18723314
TI  - Patient-reported outcomes as a component of the primary endpoint in a double
      blind, placebo-controlled trial in advanced pancreatic cancer.
AB  - In this randomized, double-blind, placebo-controlled study comparing
      gemcitabine+tipifarnib (G+t) or gemcitabine+placebo (G+p) in patients with
      pancreatic cancer, the primary endpoint of time to deterioration (TTD) was based
      primarily on patient-reported outcomes. Deterioration was defined as death or
      worsening of disease-related symptoms, based on patient-reported outcomes of pain
      intensity and analgesic use in a daily diary, plus investigator-rated weekly
      performance status. Secondary endpoints included survival and safety. Two hundred
      and forty-four patients were treated for a total of 4780 weeks, during which the
      diary was completed daily. Overall, the completion of the diary was found to be
      feasible: patients completed approximately 95% of scheduled diary entries.
      Baseline characteristics were well balanced between the two treatment arms. The
      primary endpoint of TTD was not significantly different between the G+t arm (69
      days) and the G+p arm (91 days, P=0.40). Survival was not significantly different
      between the G+t arm (202 days) and the G+p arm (221 days, P=0.66). The
      combination of G+t had an acceptable toxicity profile, with primarily neutropenia
      and thrombocytopenia. Methodologically, measurement of patient-reported outcomes
      is feasible and useful in assessing the effect of anti-cancer therapy in
      pancreatic cancer if comprehensive initial and ongoing training is provided to
      all people involved, including not only the patients but also the study
      personnel.

PMID- 18723315
TI  - Performance of the adolescent obsessive-compulsive scale in a community survey.
AB  - Obsessive-compulsive behavior was studied in a cohort of N=570 subjects who had
      been assessed at three times between adolescence and young adulthood. Based on
      the Youth Self-Report (YSR) and the Young Adult Self-Report (YASR), the
      adolescent obsessive-compulsive scale (AOCS) was defined. At each of the three
      assessments, subjects scoring above the cut-off score of the 90th percentile of
      the AOCS were identified and compared to the rest of the sample serving as
      control group. The risk group was clearly more abnormal in both domains of
      internalizing and externalizing across time. Various psychiatric disorders in
      young adulthood were predicted by the AOCS. However, concomitant general
      psychopathology also contributed strongly to the prediction. Parent and youth
      agreement on group membership was rather low. Stability of group assignment
      across time was significantly increased. The AOCS is a promising instrument both
      for epidemiological and clinical studies. Its content and predictive validity
      deserves further studies.

PMID- 18723316
TI  - The administrative population report on children with developmental delays in
      Taiwan, 2003 through 2007.
AB  - This paper was a population study with developmental delays and it included an
      examination of the trends the overtime change trend and reported channels of this
      group of people in Taiwan. We analyzed data for the present study mainly from the
      Department of Statistics, Ministry of the Interiors, Taipei, Taiwan: "Number of
      early intervention for children with developmental delays in Taiwan" from 2003
      through 2007. The reported number of children with developmental delays slightly
      increased from 13,231 to 14,250 (increase rate=7.7%) from the year of 2003
      through 2007 in Taiwan. More than one-half of children with developmental delays
      were reported during the age 3-5 years. Aged 0-2 group has the highest increasing
      reported numbers in the previous 5 years which changed dramatically increased
      from 4139 (31.3%) in 2003 to 6201 (43.5%) in 2007 (increase rate=49.8%). The
      medical care setting was the main reported channel of the children with
      developmental delays and the results also showed that the reported prevalence of
      the aged 0-2 developmentally delayed children was 57.4-102.2 per 10,000 children;
      aged 3-5 was 79.0-105.1 per 10,000 children from the year 2003-2007 in Taiwan.
      The present concluded that early intervention based on the precise affected
      population would provide important supports for families of children with
      developmental delays. Therefore, the health care system should be strengthened to
      increase the proportion of children identified at the earlier age and to decrease
      the variability in the age at identification for most of the conditions of
      children with developmental delays.

PMID- 18723317
TI  - Neuromorphic VLSI vision system for real-time texture segregation.
AB  - The visual system of the brain can perceive an external scene in real-time with
      extremely low power dissipation, although the response speed of an individual
      neuron is considerably lower than that of semiconductor devices. The neurons in
      the visual pathway generate their receptive fields using a parallel and
      hierarchical architecture. This architecture of the visual cortex is interesting
      and important for designing a novel perception system from an engineering
      perspective. The aim of this study is to develop a vision system hardware, which
      is designed inspired by a hierarchical visual processing in V1, for real time
      texture segregation. The system consists of a silicon retina, orientation chip,
      and field programmable gate array (FPGA) circuit. The silicon retina emulates the
      neural circuits of the vertebrate retina and exhibits a Laplacian-Gaussian-like
      receptive field. The orientation chip selectively aggregates multiple pixels of
      the silicon retina in order to produce Gabor-like receptive fields that are tuned
      to various orientations by mimicking the feed-forward model proposed by Hubel and
      Wiesel. The FPGA circuit receives the output of the orientation chip and computes
      the responses of the complex cells. Using this system, the neural images of
      simple cells were computed in real-time for various orientations and spatial
      frequencies. Using the orientation-selective outputs obtained from the multi-chip
      system, a real-time texture segregation was conducted based on a computational
      model inspired by psychophysics and neurophysiology. The texture image was
      filtered by the two orthogonally oriented receptive fields of the multi-chip
      system and the filtered images were combined to segregate the area of different
      texture orientation with the aid of FPGA. The present system is also useful for
      the investigation of the functions of the higher-order cells that can be obtained
      by combining the simple and complex cells.

PMID- 18723318
TI  - Echocardiography in translational research: of mice and men.
AB  - Mice are increasingly used in cardiovascular research, and echocardiography is
      ideally suited to evaluate their cardiac phenotype. This review describes the
      current use of mice echocardiography and focuses on some of its applications in
      both basic and clinical science.

PMID- 18723319
TI  - Usefulness of dobutamine stress echocardiography with Tissue Doppler imaging for
      the evaluation and follow-up of patients with repaired tetralogy of Fallot.
AB  - BACKGROUND: The longstanding pulmonary regurgitation in patients with repaired
      tetralogy of Fallot (RTOF) results in right ventricular (RV) failure. The
      estimation of RV function and reserve in these patients is of great importance,
      especially for the determination of the proper timing of pulmonary valve
      replacement. Tissue Doppler imaging (TDI) of the tricuspid annulus has been
      proved a valuable tool in the evaluation of these patients. Dobutamine stress
      echocardiography (DSE) in low doses detects the contractility reserve of cardiac
      myocytes. The aim of our study was to estimate RV reserve in patients with RTOF
      with the use of DSE and TDI and to examine whether this is related to baseline
      TDI indices of the tricuspid annulus. METHODS: We studied 21 patients with RTOF
      and 21 age- and gender-matched controls with TDI Doppler at the tricuspid annulus
      during DSE. TDI measurements were made at baseline and at infusion rates of 10
      and 20 microg x kg x min. RESULTS: Patients with RTOF had lower values of TDI
      indices at baseline and during dobutamine infusion and smaller dobutamine-induced
      increase of Sa (DeltaSa) (3.8 +/- 1.2 vs. 10.8 +/- 3.6 cm/sec, P < .001) and Aa
      (3.5 +/- 2.2 vs. 10.0 +/- 3.2 cm/sec, P < .001). A value of DeltaSa < or = 6
      cm/sec clearly discriminated patients from controls and could be predicted by
      values of Sa < 11.5 cm/sec with sensitivity of 95% and specificity of 100%.
      CONCLUSIONS: In patients with RTOF, impaired RV contractile reserve can be
      documented with TDI of tricuspid annular motion during DSE and is predicted by
      TDI indices at rest. Its serial estimation may contribute to optimal timing of
      reoperation.

PMID- 18723320
TI  - Application of quantitative tissue velocity imaging to evaluate left ventricular
      early diastolic dysfunction in dogs with heart failure due to rapid ventricular
      pacing.
AB  - BACKGROUND: The authors assessed the capability of quantitative tissue velocity
      imaging (QTVI) to detect left ventricular (LV) early diastolic dysfunction
      (LVEDDY) in a canine model. METHODS: Rapid ventricular pacing (RVP) at 240
      beats/min was maintained in 14 dogs for 2 weeks. Echocardiography, cardiac
      catheterization, and endomyocardial biopsies were performed at baseline, during
      pacing, and at 2 weeks. QTVI, conventional echocardiographic, and LV pressure and
      pathologic indices were measured, and correlations were analyzed during the
      progressive development of diastolic dysfunction produced by RVP. Receiver
      operating characteristic (ROC) curves of QTVI parameters were analyzed to
      identify predictors of LVEDDY. RESULTS: The onset of LVEDDY occurred 24 hours
      after RVP initiation. Most of the QTVI indices were altered at 12 or 24 hours
      after RVP onset. New parameters were identified, including time-R and time-E',
      which are the times from aortic valve closure to peak isovolumetric relaxation
      (R) and peak early diastolic velocity (E'), respectively, as well as the ratios
      of peak myocardial systolic velocity (S') and peak E' to R (S'/R and E'/R,
      respectively), which significantly changed during RVP. These parameters were
      correlated with LV -dp/dt(max) or LV end-diastolic pressure, but time-R, time-E',
      and S'/R were not correlated with heart rate. In addition, using ROC analysis,
      time-R had the largest area under the curve to predict LVEDDY after RVP.
      CONCLUSIONS: QTVI is a sensitive and specific quantitative method that can be
      used for the early detection of LVEDDY under tachycardic conditions. The novel
      indices described here, including time-R, time-E', and S'/R, can serve as
      effective, noninvasive, possibly heart rate independent LVEDDY markers.

PMID- 18723321
TI  - Development of a computer assisted system aimed at RFA liver surgery.
AB  - Radio frequency ablation (RFA) is a minimally invasive treatment for either
      hepatocellular carcinoma or metastasis liver carcinoma. In order to resect large
      lesions, the surgeon has to perform multiple time-consuming destruction cycles
      and reposition the RFA needle for each of them. The critical step in handling a
      successful ablation and preventing local recurrence is the correct positioning of
      the needle. For small tumors, the surgeon places the middle of the active needle
      tip in the center of the tumor under intra-operative ultrasound guidance. When
      one application is not enough to cover the entire tumor, the surgeon needs to
      repeat the treatment after repositioning of the needle, but US guidance is
      obstructed by the opacity stemming from the first RFA application. In this case
      the surgeon can only rely on anatomical knowledge and the repositioning of the
      RFA needle becomes a subjective task limiting the treatment accuracy. We have
      developed a computer assisted surgery guidance application for this repositioning
      procedure. Our software application handles the complete process from
      preoperative image analysis to tool tracking in the operating room. Our framework
      is mostly used for this RFA procedure, but is also suitable for any other medical
      or surgery application.

PMID- 18723322
TI  - Validity of segmental multiple-frequency bioelectrical impedance analysis to
      estimate body composition of adults across a range of body mass indexes.
AB  - OBJECTIVE: We compared body composition estimates using an eight-electrode,
      segmental, multiple-frequency bioelectrical impedance analysis (segmental MF-BIA)
      and dual x-ray absorptiometry (DXA) in a group of healthy adults with a range of
      body mass indexes (BMIs). METHODS: Percentage of body fat (%BF), fat-free mass,
      and fat mass assessed by DXA and segmental MF-BIA in 132 healthy adults were
      classified by normal (N; 18.5-24.9 kg/m(2)), overweight (OW; 25-29.9 kg/m(2)),
      and obese (OB; 30-39.9 kg/m(2)) BMI. RESULTS: Compared with DXA, segmental MF-BIA
      overestimated %BF in the OB BMI group (3.4%; P < 0.0001). MF-BIA overestimated
      %BF among men (0.75%; P < 0.006) and women (0.87%; P < 0.006) and underestimated
      it in the N BMI group (-1.56%; P < 0.0001); %BF was not different between methods
      in the OW BMI group. Error in %BF determined by segmental MF-BIA and DXA
      increased as %BF increased (r = 0.42, P < 0.0001). Waist circumference was the
      only significant predictor of systematic error in %BF between MF-BIA and DXA (r =
      0.60, P < 0.0001). CONCLUSION: Eight-electrode, segmental MF-BIA is a valid
      method to estimate %BF in adults with BMI classified as N and OW, but not as OB.
      Estimation of trunk resistance with current segmental MF-BIA devices may explain
      the underestimation of %BF in the adults with OB BMI. Further examination of the
      effect of waist circumference and body fat distribution on the accuracy of BIA
      measurements is warranted.

PMID- 18723323
TI  - Short-chain fatty acids and trichostatin A alter tight junction permeability in
      human umbilical vein endothelial cells.
AB  - OBJECTIVE: The short-chain fatty acids (SCFAs), butyrate, propionate, and
      acetate, produced by bacterial fermentation of dietary fiber, can modulate the
      transcription of certain genes by inhibiting histone deacetylase in colonocytes
      and several other cell types in vitro. We previously reported that butyrate
      decreases tight junction permeability by activating lipoxygenase (LOX) in
      intestinal monolayer cells. In the present study, we evaluated the effects of
      SCFAs on tight junction permeability in an endothelial cell culture and their
      possible mechanisms of action via histone deacetylase inhibitor activity. We also
      investigated the factors modulating tight junction permeability. METHODS: The
      effects of butyrate, propionate, and acetate on tight junction permeability in
      human umbilical vein endothelial cells were examined using Transwell chamber
      cultures. The contributions of inducible nitric oxide synthase (NOS), endothelial
      NOS, estrogen receptor, cyclo-oxygenase, and LOX to SCFAs' effects were also
      evaluated. The effects of SCFAs were compared with those of trichostatin A, a
      typical histone deacetylase inhibitor. RESULTS: Low concentrations of butyrate
      and propionate decreased paracellular permeability without inducing cell damage.
      However, acetate decreased paracellular permeability in a concentration-dependent
      manner. An estrogen receptor antagonist attenuated the effects of SCFAs on tight
      junction permeability. The influences of inducible NOS, cyclo-oxygenase, and LOX
      inhibitors and the expressions of cyclo-oxygenase and LOX mRNAs were different
      for each SCFA. Trichostatin A slightly decreased paracellular permeability when
      used at lower concentrations, but higher concentrations of trichostatin A
      increased permeability. CONCLUSION: The SCFAs play an important role in the
      assembly of tight junctions in normal vascular endothelial cells.

PMID- 18723324
TI  - Association of low serum selenium with anemia among adolescent girls living in
      rural Vietnam.
AB  - OBJECTIVE: We investigated the prevalence of anemia and deficiency in trace
      elements in adolescent girls living in rural Vietnam. METHODS: Two hundred forty
      five adolescent girls 11-17 y of age from three schools in rural province of Ha
      Nam, Vietnam, were assessed. RESULTS: The prevalence of anemia was 20.4%. The
      incidences of low serum selenium (Se), zinc, and copper in subjects were 15.9%,
      26.5%, and 4.1%, respectively. The parameter significantly associated with anemia
      was the low serum levels of Se and vice versa (odds ratio [OR] 5.36, 95%
      confidence interval [CI] 2.57-11.18, P < 0.0001). Other risk factors for anemia
      were a body mass index <17.00 kg/m(2) (OR 2.72, 95% CI 1.37-5.37, P = 0.004) and
      years of age (OR 1.35, 95% CI 1.14-1.59, P < 0.001). A body mass index <17.00
      kg/m(2) (OR 2.65, 95% CI 1.25-5.61, P = 0.011) was also found to be a risk factor
      for low serum Se. CONCLUSION: The findings of the present study demonstrate that
      low serum Se is independently associated with anemia in adolescent girls living
      in rural Vietnam. Interventions are required to gain insight into the potential
      role of Se on prevention and control of anemia.

PMID- 18723325
TI  - Phenotypic concordance in 70 families with IGE-implications for genetic studies
      of epilepsy.
AB  - INTRODUCTION: A crucial issue in the genetic analysis of idiopathic generalized
      epilepsy (IGE) is deciding on the phenotypes that are likely to give the greatest
      power to detect predisposing variants. A complex inheritance pattern and unclear
      nature of the genotype-phenotype correlation makes this task difficult. In the
      absence of much definitive genetic information to clarify this correlation, we
      inferred the putative effects of predisposing genes by studying the clustering of
      various phenotypic features, both clinical and electrophysiological, within
      families. METHODS: We examined the distribution of clinical features among
      relatives of a proband in 70 French-Canadian families with a minimum of two
      affected individuals with a clear diagnosis of IGE and then, using concordance
      analysis, identified the relative genetic influences on IGE syndrome, seizure
      type, age-at-onset, and EEG features. RESULTS: The mean number of affected
      individuals with IGE per family was three. One-third of relatives had the same
      syndrome as the proband. 16-22.5% of relatives of a proband with one of the
      absence syndromes had juvenile myoclonic epilepsy (JME). Conversely, 27% of
      relatives of probands with JME had an absence syndrome. 15% of relatives
      displayed the exact constellation of seizure types as the proband. Concordance
      analysis demonstrated greater clustering within families of IGE syndrome, seizure
      type, and age-at-onset than would be expected by chance. Significant concordance
      was not evident for EEG features. DISCUSSION: There was a large degree of
      clinical heterogeneity present within families. However we found evidence for
      clustering of a number of clinical features. Further refinement of the phenotypes
      used in genetic studies of complex IGE is necessary for progress to be made.

PMID- 18723326
TI  - Novel p.M1T and recurrent p.G301S mutations in cathepsin C in a Japanese patient
      with Papillon-Lefevre syndrome: implications for understanding the
      genotype/phenotype relationship.

PMID- 18723327
TI  - Antimicrobial susceptibility and molecular epidemiology of Streptococcus
      pneumoniae isolated from Shanghai, China.
AB  - In this study, the antimicrobial resistance profiles of pneumococci isolated from
      respiratory specimens of patients from Shanghai, China, in 2004 and 2005 are
      described. Non-susceptible rates to penicillin and erythromycin among paediatric
      isolates (n=122) were 63.1% and 94.3%, respectively, whilst those of adult
      isolates (n=39) were 20.5% and 69.2%, respectively (P<0.0001 and P<0.0002).
      Nineteen serotypes were identified among 103 tested strains, 73.8% of which
      belonged to 19F, 14, 23F, 6B and 19A. The erm(B) gene was detected in 51
      erythromycin-resistant strains (52.6%), the mef(E) gene in 5 strains (5.2%) and
      both erm(B) and mef(E) in 41 strains (42.3%). Among 45 sequence types (STs)
      determined by multilocus sequence typing (MLST) in these 103 isolates, 25 STs
      were new assignments and 9 STs contained 10 new alleles. On the other hand, 46
      (68.7%) of 67 penicillin-non-susceptible S. pneumoniae and 51 (52.6%) of 97
      macrolide-resistant S. pneumoniae were characterised as belonging to four
      international resistant clonal complexes, Taiwan(19F)-14, Spain(23F)-1, Spain(6B)
      2 and Taiwan(23F)-15. Our findings indicate that the spread of international
      resistant clones played a predominant role in the emergence and increase of
      resistance in Shanghai. Conjugate vaccination may be a promising method to
      prevent the increase in pneumococcal resistance.

PMID- 18723329
TI  - New antibiotic agents for bloodstream infections.
AB  - Infections due to multidrug-resistant pathogens have shown a dramatic worldwide
      increase in prevalence. Bloodstream infections (BSIs) represent an important
      cause of morbidity and mortality in hospitalised patients. Research in the field
      led to the introduction of several novel antibiotic agents in the fight against
      bacterial pathogens. New antibiotics used against Gram-positive bacteria, mainly
      meticillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci,
      include daptomycin, linezolid, quinupristin/dalfopristin and semisynthetic
      lipoglycopeptides. Among the Gram-negative bacteria, extended-spectrum beta
      lactamase-producing Enterobacteriaceae as well as highly resistant Pseudomonas
      and Acinetobacter isolates are of particular concern. Doripenem is a recently
      approved carbapenem. Polymyxins are reconsidered as valuable therapeutic options
      for Gram-negative infections. Tigecycline, a glycylcycline, and ceftobiprole, a
      novel cephalosporin under investigation, have activity both against Gram-positive
      and Gram-negative organisms. In addition to the above agents, alternative
      treatment approaches that require further investigation have also been introduced
      into clinical practice. These include antibiotic lock therapy and continuous
      intravenous administration of antibiotics. In this article, we review the above
      treatment options for BSIs based on current clinical evidence. Comparative trials
      specifically focusing on patients with bacteraemia were generally not performed;
      however, a proportion of patients from the reported studies did have bacteraemia.

PMID- 18723328
TI  - Serotype 6C is associated with penicillin-susceptible meningeal infections in
      human immunodeficiency virus (HIV)-infected adults among invasive pneumococcal
      isolates previously identified as serotype 6A in South Africa.
AB  - A newly described pneumococcal serotype (6C) is indistinguishable from serotype
      6A when using the conventional Quellung serotyping method. Serotype 6A isolates
      were screened by polymerase chain reaction (PCR) for the wciN region of the
      capsular locus. This study detected serotype 6C among invasive pneumococcal
      disease (IPD) isolates from national laboratory-based surveillance (2005-2006) in
      South Africa. No serotype 6C isolates were identified among 23 serotype 6A cases
      from children enrolled in a 9-valent pneumococcal conjugate vaccine trial (1998
      2005). Of 8167 IPD cases reported nationally, viable isolates were available for
      serotyping in 87% of cases (n=7080). Quellung serotyping identified 608 serotype
      6A isolates, of which 606 were further tested for serotype 6C. PCR confirmed
      serotype 6C in 5% (30/606) of the isolates tested. Serotype 6C isolates were:
      less likely than 6A to cause disease in children compared with adults (6/30 (20%)
      vs. 311/550 (57%); P<0.001); more likely to cause laboratory-confirmed meningitis
      (15/30 (50%) vs. 167/578 (29%); P=0.01); and more likely to demonstrate
      susceptibility to penicillin (non-susceptibility 0/30 vs. 129/578 (22%);
      P=0.004). No association with gender, human immunodeficiency virus (HIV) co
      infection or case fatality rate was observed. Although serotype 6C prevalence was
      low, its epidemiology may differ from the other serogroup 6 pneumococci. Our data
      from the vaccine efficacy trial suggest that cross-protection of the conjugate
      vaccine is against true serotype 6A strains.

PMID- 18723330
TI  - Characterization of local environments in crystalline borophosphates using single
      and double resonance NMR.
AB  - (11)B and (31)P magic-angle spinning as well as (11)B{(31)P} and (31)P{(11)B}
      rotational echo double resonance (REDOR) NMR have been applied to characterize
      the local environments in the crystalline borophosphates K(3)[BP(3)O(9)(OH)(3)],
      NH(4)[ZnBP(2)O(8)] and Rb(3)[B(2)P(3)O(11)(OH)(2)]. Dipolar second moment values
      extracted from the REDOR curves at short evolution times (DeltaS/S(0) < or = 0.2)
      are in reasonable agreement with those calculated from the internuclear distances
      in the corresponding crystal structures. In particular, the method is found to be
      useful for distinguishing between boron and phosphorus local environments with
      different numbers of B-O-P connectivities, making REDOR a well-suited tool for
      medium-range order investigations in glasses.

PMID- 18723331
TI  - Preparation and characterization of complexes of liposomes with gold
      nanoparticles.
AB  - Gold nanoparticles (Au NPs), which are extremely useful materials for imaging and
      photothermal therapy, typically require a drug delivery system to transport them
      to the affected tissue and into the cells. Since liposomes are approved as drug
      carriers, complexes of liposomes with Au NPs were considered ideal solutions to
      deliver Au NPs to the target site in vivo. In this study, we prepared complexes
      of various liposomes with Au NPs via physical absorption and characterized them.
      The time dependency of the surface plasmon resonance of this complex, which is a
      unique property of Au NPs, shows that the liposomes promote the formation of
      stable dispersions of Au NPs under isotonic conditions, even though intact Au NPs
      aggregate immediately. From a release assay of calcein from liposomes and
      transmission electron microscopy analysis, the Au NPs were complexed with
      liposomes without membrane disruption. These complexes could be formed by using
      cationic liposomes and polyethylene glycol-modified liposomes, as well as by
      using phosphatidylcholine liposomes, which are useful for drug and gene delivery.
      We proposed this kind of complex as a nanomedicine with diagnostic and
      therapeutic ability.

PMID- 18723332
TI  - [Quality of life in children with epilepsy: a review].
AB  - Health-related quality of life (HRQOL) is a multidimensional construct, without
      general agreement on the number of domains and the content of each domain. In
      children with epilepsy, the HRQOL evaluation includes both nonspecific aspects,
      such as behavioral, psychological and cognitive difficulties and the impact of a
      chronic pediatric illness on the child and its family and specific aspects, such
      as the perception of the severity of the seizures and of the undesirable effects
      of the antiepileptic treatments, as well as the social impact of a negative
      attitude toward epilepsy. The present article presents a review of the methods
      proposed for the assessment of HRQOL in children with epilepsy. Most methods rely
      on parental reports; however, there is an increasing effort to develop tools
      taking the child's point of view into account. HRQOL tools have often been used
      in clinical trials and, especially, to evaluate the surgical treatments of
      epilepsy. For the clinician, HRQOL tools may be a preliminary approach to the
      patient's problems to be interpreted in relation to the patient's medical,
      psychological, cognitive, social and familial context. In France, few large-scale
      studies on HRQOL in children with epilepsy have been conducted. We present the
      preliminary results of a French study based on parental reports.

PMID- 18723333
TI  - Unbiased estimation of the calcaneus volume using the Cavalieri principle on
      computed tomography images.
AB  - The size and shape of tarsal bones are especially relevant when considering some
      orthopedic diseases such as clubfoot. For this reason, the measurements of the
      tarsal bones have been the subject of many studies, none of which has used
      stereological methods to estimate the volume. In the present stereological study,
      we estimated the volume of calcaneal bone of normal feet and dry bones. We used a
      combination of the Cavalieri principle and computer tomographic scans taken from
      eight males and nine dry calcanei to estimate the volumes of calcaneal bones. The
      mean volume of dry calcaneal bones was estimated, producing mean results using
      the point-counting method and Archimedes principle being 49.11+/-10.7 or 48.22+/
      11.92 cm(3), respectively. A positive correlation was found between
      anthropometric measurements and the volume of calcaneal bones. The findings of
      the present study using the stereological methods could provide data for the
      evaluation of normal and pathological volumes of calcaneal bones.

PMID- 18723335
TI  - A real-life cost-effectiveness evaluation of budesonide/formoterol maintenance
      and reliever therapy in asthma.
AB  - OBJECTIVE: To evaluate direct asthma-related costs in Swedish primary care in a
      real-life setting. DESIGN: 12-month open-label study. SETTING: Swedish primary
      care in a real-life setting. PARTICIPANTS: 1776 patients with persistent asthma.
      INTERVENTIONS: Patients with persistent asthma were randomised to one of three
      treatments: a free adjustable combination of budesonide (100-400
      microg/inhalation) and formoterol (4.5 or 9 microg/inhalation) via separate
      inhalers plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or
      80/4.5 microg, two inhalations twice daily) plus terbutaline as needed;
      budesonide/formoterol (160/4.5 microg or 80/4.5 microg, one inhalation twice
      daily or two inhalations once daily), for maintenance plus additional inhalations
      as needed. Doses depended on previous inhaled corticosteroid dose. Patients
      attended the clinic at 0, 1.5, and 12 months. Telephone interviews were conducted
      at 4, 6, 8, and 10 months. MAIN OUTCOME MEASURES: The primary endpoint was direct
      asthma-related healthcare costs. RESULTS: Statistically significant reductions in
      annual direct costs per patient were observed with budesonide/formoterol
      maintenance and reliever therapy compared with the free adjustable combination of
      budesonide and formoterol (-13%, P<0.001) and fixed-dose budesonide/formoterol
      plus terbutaline (-20%, P<0.001). Time to first severe exacerbation did not
      differ significantly across treatment groups, with a mean reduction of 28% versus
      the free adjustable combination of budesonide and formoterol (P=0.076). Patients
      receiving budesonide/formoterol maintenance and reliever therapy used a
      significantly lower daily dose of budesonide compared with the conventional
      (P<0.001). CONCLUSIONS: This study reports direct cost savings with
      budesonide/formoterol maintenance and reliever therapy compared with conventional
      treatment regimens with at least equivalent efficacy.

PMID- 18723334
TI  - HRCT and histopathological evaluation of fibrosis and tissue destruction in IPF
      associated with pulmonary emphysema.
AB  - Idiopathic pulmonary fibrosis has been associated with emphysema in cigarette
      smokers as a new clinical entity: combined pulmonary fibrosis and emphysema
      (CPFE). In order to compare histomorphometrical, roentgenological and
      immunohistochemical aspects of usual interstitial pneumonia (UIP) with and
      without associated pulmonary emphysema, 17 patients with biopsy-proven UIP were
      evaluated. Morphometrical evaluation of lung parenchyma destruction was used to
      divide patients in two subgroups: emphysema/UIP (n=9) and UIP alone (n=8); four
      patients with biopsy-proven emphysema without fibrosis were also evaluated. At
      HRTC scan, emphysematous lesions were prevalent in the upper fields of both
      emphysema/UIP and emphysema groups and the distribution of fibrotic lesions was
      similar in emphysema/UIP compared to UIP alone. The semiquantitative
      histopathological fibrotic score was also similar in emphysema/UIP and UIP alone.
      In addition, the expression of tumor necrosis factor (TNF)-alpha, matrix
      metalloproteinase (MMP)-2, MMP-9, MMP-7 and membrane type 1-metalloproteinase
      (MT1-MMP) by fibroblasts of myofibroblastic foci was similar in emphysema/UIP and
      UIP alone patients. In contrast, fibroblasts in areas of parenchymal destruction
      of emphysema/UIP expressed MMP-2, MMP-9, MMP-7 and MT1-MMP at variable but
      significantly higher levels when compared to emphysema subjects, in the presence
      of similar levels of TIMP-1, TIMP-2 and TNF-alpha. Fibrotic and emphysematous
      lesions in emphysema/UIP patients appear to follow the roentgenological and
      histopathological patterns expected for either UIP or emphysema. Interstitial
      fibroblast activation is more pronounced in the areas of lung destruction in
      emphysema/UIP compared to those with emphysema alone, as for exaggerated tissue
      remodeling.

PMID- 18723336
TI  - Direct comparison of fluorescence- and bioluminescence-based resonance energy
      transfer methods for real-time monitoring of thrombin-catalysed proteolytic
      cleavage.
AB  - In this study, a representative FRET system (CFP donor and YFP acceptor) is
      compared with the BRET(2) system (Renilla luciferase donor, green fluorescent
      protein(2) (GFP(2)) acceptor and coelenterazine 400a substrate). Cleavage of a
      thrombin-protease-sensitive peptide sequence inserted between the donor and
      acceptor proteins was detected by the RET signal. Complete cleavage by thrombin
      changed the BRET(2) signal by a factor of 28.9+/-0.2 (R.S.D. (relative standard
      deviation), n=3) and the FRET signal by a factor of 3.2+/-0.1 (R.S.D., n=3). The
      BRET(2) technique was 50 times more sensitive than the FRET technique for
      monitoring thrombin concentrations. Detection limits (blank signal+3sigma(b),
      where sigma(b)=the standard deviation (S.D.) of the blank signal) were calculated
      to be 3.05 and 0.22nM thrombin for FRET and BRET(2), respectively. This direct
      comparison suggests that the BRET(2) technique is more suitable than FRET for use
      in proximity assays such as protease cleavage assays or protein-protein
      interaction assays.

PMID- 18723337
TI  - Shear acoustic wave biosensor for detecting DNA intrinsic viscosity and
      conformation: a study with QCM-D.
AB  - Direct biosensors are devices operating by monitoring the amount of surface-bound
      analyte. In this work a new approach is presented where a label-free acoustic
      biosensor, based on a QCM-D device, and solution viscosity theory, are used to
      study DNA intrinsic viscosity. The latter is quantitatively related to the DNA
      conformation and specifically the molecule's shape and size, in a manner that is
      independent of the amount of bound DNA mass. It is shown that acoustic
      measurements can clearly distinguish between ds-DNA of same shape (straight rod)
      but various sizes (from 20 to 198bp (base pairs)) and same mass and size (90bp)
      but various shapes ("straight", "bent", "triangle"). These results are discussed
      in the broader context of "coil" and sphere-like molecules detected on surfaces.
      A mathematical formula is presented relating the length of straight, surface
      protruding DNA to the acoustic ratio DeltaD/Deltaf. The development of real-time
      rapid techniques for the characterization of DNA intrinsic curvature as well as
      DNA conformational changes upon interaction with proteins is of significance to
      analytical biotechnology due to the large number of DNA sequences and potential
      DNA bending proteins involved in genome analysis and drug screening.

PMID- 18723338
TI  - Mismatch repair gene polymorphisms and survival in invasive ovarian cancer
      patients.
AB  - AIMS: Inherited genetic factors may help partially explain variability of
      survival length amongst ovarian cancer patients. Of particular interest are genes
      involved in DNA repair, specifically those involved in mismatch repair (MMR). The
      aim of this study was to investigate the possible association between the common
      variants in MMR genes and invasive ovarian cancer overall survival.
      METHOD/RESULTS: We examined associations between 44 variants that tag the known
      common variants (minor allele frequency 0.05) in seven MMR genes (MLH1, MLH3,
      MSH2, MSH3, MSH6, PMS1 and PMS2) and survival of invasive ovarian cancer patients
      in three case-control studies from United Kingdom (UK), Denmark and California of
      United States of America (USA). DNA from up to 1495 women were genotyped. The
      genotypes of each polymorphism were tested for association with survival using
      Cox regression analysis stratified by study. A nominally significant association
      (P=0.04) between genotype and ovarian cancer survival was observed for rs2228006
      in PMS2. The per-rare allele hazard ratio (HR 95%CI) was 0.84 (0.71-0.99),
      however, it was not significant after adjusting for multiple covariants (P=0.47).
      When the analyses were restricted to serous type ovarian cancer, two SNPs showed
      marginal significant associations; the per-rare allele HR was 1.3 (1.05-1.6)
      (P=0.02) for rs1799977 in MLH1 and 1.4 (1.03-1.9) (P=0.04) for rs6151662 in MSH3.
      Neither was significant after adjusting for multiple covariants. CONCLUSION: It
      is unlikely that common variants in the MMR pathways examined have moderate
      effects on survival after diagnosis with ovarian cancer. Much larger studies
      would be needed to exclude common variants with small effects.

PMID- 18723339
TI  - Addition of receptor tyrosine kinase inhibitor to radiation increases tumour
      control in an orthotopic murine model of breast cancer metastasis in bone.
AB  - The receptor tyrosine kinase inhibitor, SU11248, was added to localised radiation
      to evaluate the response of bone metastases and to define the basic mechanism of
      radiosensitisation. Treatment with SU11248 and radiation was assessed in vitro
      using cultured 4T1 breast cancer cells and in vivo using an orthotopic 4T1 murine
      mammary tumour model of breast cancer bone metastasis. Cultured 4T1 cells treated
      with SU11248 (1 microM) and radiation (10 Gy) showed an almost 7.5-fold increase
      in caspase-mediated apoptosis after 24 h of incubation, compared to either
      treatment alone. Mice treated with SU11248 (40 mg/kg/daily) and radiation (15
      Gy/single-dose) had a relatively greater reduction in tumour growth, bone
      osteolysis, osteoclast maturation and microvessel density. Combined modality
      treatment resulted in improvements in behavioural pain assessment scores and
      normalisation of neurochemical changes in the spinal cord receiving primary
      afferent innervation from tumour-bearing femora. Our study demonstrates that
      SU11248 enhances the radiation control of metastatic breast tumours in bone and
      tumour-induced pain.

PMID- 18723340
TI  - Modification of paper properties by the pretreatment of wastepaper pulp with
      Graphiumputredinis, Trichodermaharzianum and fusant xylanases.
AB  - Graphiumputredinis, Trichodermaharzianum and fusant were used in the present
      study to produce extracellular xylanases, an important industrial enzyme used in
      pulp and paper industry produced in a minimal medium supplemented with oat spelt
      xylan (1%, w/v) pH 7.0 at 27+/-2 degrees C. The enzyme was purified to
      homogeneity by DEAE-Cellulose and Superdex 75 FPLC column, respectively. The
      enzyme was found to be a monomer as determined by SDS gel electrophoresis. The
      optimum pH and temperature for purified G. putredinis, T. harzianum and fusant
      xylanases were 5.0-6.0 and 50-70 degrees C, respectively. Pretreatment of paper
      pulp with G. putredinis, T. harzianum and fusant xylanases decreased pulp kappa
      number. Xylanases particularly that of fusant at 5 IU/g pulp concentration and
      1.5% pulp consistency at 60 degrees C for 18 h followed by EDED process yielded
      good quality paper from waste paper pulp. A significant increase in pulp
      brightness and improvement in various pulp properties, viz. burst capacity,
      thickness and bulkness of the treated pulp were observed in comparison to the
      conventional chemical bleaching. Easy purification and high stability of these
      enzymes makes it amicable for industrial applications.

PMID- 18723341
TI  - An organic-solvent-tolerant esterase from thermophilic Bacillus licheniformis S
      86.
AB  - A thermophile, halotolerant and organic-solvent-tolerant esterase producer
      Bacillus sp. S-86 strain previously isolated was found to belong to Bacillus
      licheniformis species through morphological, biochemical, 16S rRNA gene sequence
      analyses and rDNA intergenic spacers amplification (ITS-PCR). The strain can grow
      at 55 degrees C in presence of C2-C7 alkanols (log P=-0.86 to 2.39), and NaCl
      concentrations up to 15% (w/v). This bacterium showed optimal growth and esterase
      production at 50 degrees C. Two different molecular weight esterase activities
      were detected in zymographic assays. PMSF inhibited type I esterase activity,
      showing no inhibitory effect on type II esterase activity. B. licheniformis S-86
      was able to grow in presence of hydroxylic organic-solvents like propan-2-ol,
      butan-1-ol and 3-methylbutan-1-ol. At a sub-lethal concentration of these
      solvents (392 mmoll(-1) propan-2-ol; 99 mmol l(-1) butan-1-ol, 37 mmol l(-1) 3
      methylbutan-1-ol), adequate to produce 50% cell growth inhibition at 50 degrees
      C, an increment between 1.9 and 2.3 times was observed in type I esterase
      production, and between 2.2 and 3.1 times in type II esterase production.

PMID- 18723342
TI  - Ethanol production from cotton-based waste textiles.
AB  - Ethanol production from cotton linter and waste of blue jeans textiles was
      investigated. In the best case, alkali pretreatment followed by enzymatic
      hydrolysis resulted in almost complete conversion of the cotton and jeans to
      glucose, which was then fermented by Saccharomyces cerevisiae to ethanol. If no
      pretreatment applied, hydrolyses of the textiles by cellulase and beta
      glucosidase for 24 h followed by simultaneous saccharification and fermentation
      (SSF) in 4 days, resulted in 0.140-0.145 g ethanol/g textiles, which was 25-26%
      of the corresponding theoretical yield. A pretreatment with concentrated
      phosphoric acid prior to the hydrolysis improved ethanol production from the
      textiles up to 66% of the theoretical yield. However, the best results obtained
      from alkali pretreatment of the materials by NaOH. The alkaline pretreatment of
      cotton fibers were carried out with 0-20% NaOH at 0 degrees C, 23 degrees C and
      100 degrees C, followed by enzymatic hydrolysis up to 4 days. In general, higher
      concentration of NaOH resulted in a better yield of the hydrolysis, whereas
      temperature had a reverse effect and better results were obtained at lower
      temperature. The best conditions for the alkali pretreatment of the cotton were
      obtained in this study at 12% NaOH and 0 degrees C and 3 h. In this condition,
      the materials with 3% solid content were enzymatically hydrolyzed at 85.1% of the
      theoretical yield in 24 h and 99.1% in 4 days. The alkali pretreatment of the
      waste textiles at these conditions and subsequent SSF resulted in 0.48 g
      ethanol/g pretreated textiles used.

PMID- 18723343
TI  - Role of surfactants in optimizing fluorene assimilation and intermediate
      formation by Rhodococcus rhodochrous VKM B-2469.
AB  - Biodegradation of fluorene by Rhodococcus rhodochrous VKM B-2469 was investigated
      and optimized by adding non-ionic surfactants to the liquid media. The
      utilization of 1-1.5% Tween 60 or 1% Triton X100 allowed to solubilize 1 mM
      fluorene over 150 times more than in water medium (from 9-11 microM to above 1.5
      mM at 28 degrees C). We observed that Tween 60 was useful to enhance the fluorene
      biodegradation rates further supporting R. rhodochrous VKM B-2469 growth as an
      additional carbon source and to decrease fluorene toxicity for bacterial cells
      whereas Triton X100 resulted to be toxic for this strain. An additional enzyme
      induction step before starting the bioconversion process and the increase of
      incubation temperature during fluorene bioconversion led to further improvements
      in rates of fluorene utilization and formation of its intermediates. In the
      optimized conditions 1 mM fluorene was degraded completely within 24h of
      incubation. Some intermediates in fluorene degradation built up during the
      process reaching maxima of 31% for 9-hydroxyfluorene, 2.1% for 9-fluorenone and
      1.9% for 2-hydroxy-9-fluorenone (starting from 1 mM substrate). In the presence
      of Tween 60 the appearance and following conversion of 2-hydroxy-9-fluorenone was
      observed for R. rhodochrous VKM B-2469 revealing the existence of a new pathway
      of 9-fluorenone bioconversion.

PMID- 18723344
TI  - Effect of media type and particle size on dissolved organic carbon release from
      woody filtration media.
AB  - Sequential batch leaching tests were used to evaluate the mass of DOC released
      from composted garden organics (yard waste), pine and hardwood under pseudo
      equilibrium conditions. All media showed an initial rapid decline in DOC values
      followed by a slower rate during later time periods. Greater than 50% of the DOC
      leached occurred within the initial time period (<24 h). The mass of DOC leached
      varied significantly between the materials and to a lesser degree between
      different particle size ranges. The pine had the lowest leached DOC fraction (2.8
      4.8 mg/g), while the hardwood (21-27 mg/g) and compost (13.6-32.7 mg/g) were
      significantly greater. The type and processing of the woody material incorporated
      into these systems can have a significant impact on the treated stormwater.

PMID- 18723345
TI  - Solubilization and functionalization of sulfuric acid lignin generated during
      bioethanol production from woody biomass.
AB  - Sulfuric acid lignin (SAL), which is formed as a by-product during the production
      of bioethanol from woody biomass, was solubilized and functionalized by
      hydrothermal reaction. SAL could be easily dissolved in an alkaline medium,
      especially sodium hydroxide solution, by this reaction. The soluble part of the
      reaction products (S-HSAL) could be dissolved at neutral pH. IR spectrometric
      analysis of SAL revealed that hydrophilic groups were introduced in it during the
      reaction. The dispersibility of S-HSAL was increased by sulfonation (SS-HSAL),
      and it was found to be an effective dispersant for gypsum paste.

PMID- 18723346
TI  - Discovery of amido-benzisoxazoles as potent c-Kit inhibitors.
AB  - Deregulation of the receptor tyrosine kinase c-Kit is associated with an
      increasing number of human diseases, including certain cancers and mast cell
      diseases. Interference of c-Kit signaling with multi-kinase inhibitors has been
      shown clinically to successfully treat gastrointestinal stromal tumors and
      mastocytosis. Targeted therapy of c-Kit activity may provide therapeutic
      advantages against off-target effects for non-oncology applications. A new
      structural class of c-Kit inhibitors is described, including in vitro c-Kit
      potency, kinase selectivity, and the observed binding mode.

PMID- 18723347
TI  - Design, syntheses, and structure-activity relationships of novel NPY Y5 receptor
      antagonists: 2-{3-Oxospiro[isobenzofuran-1(3H),4'-piperidin]-1'-yl}benzimidazole
      derivatives.
AB  - Design, syntheses, and structure-activity relationships of a novel class of 2-{3
      oxospiro[isobenzofuran-1(3H),4'-piperidin]-1'-yl}benzimidazole NPY Y5 receptor
      antagonists are described. The benzimidazole structures were newly designed based
      on the urea linkage of our prototype Y5 receptor antagonists (2 and 3). By
      optimizing substituents on the benzimidazole core part of the lead compound 5a,
      we were able to develop a potent, orally available, and brain-penetrable Y5
      selective antagonist (5k).

PMID- 18723348
TI  - Carbonic anhydrase inhibitors: inhibition of the beta-class enzymes from the
      fungal pathogens Candida albicans and Cryptococcus neoformans with simple anions.
AB  - The catalytic activity and inhibition of the beta-carbonic anhydrases (CAs, EC
      4.2.1.1) from the pathogenic fungi Candida albicans (Nce103) and Cryptococcus
      neoformans (Can2) with inorganic anions such as halogenides, pseudohalogenides,
      bicarbonate, carbonate, nitrate, nitrite, hydrogen sulfide, bisulfite,
      perchlorate, sulfate were investigated. The two enzymes showed appreciable CO(2)
      hydrase activity (k(cat) in the range of (3.9-8.0)x10(5)s(-1), and k(cat)/K(m) in
      the range of (4.3-9.7)x10(7)M(-1)s(-1)). Can2 was weakly inhibited by cyanide and
      sulfamic acid (K(I)s of 8.22-13.56 mM), while all other anions displayed more
      potent inhibition. Nce103 was strongly inhibited by cyanide and carbonate (K(I)s
      of 10-11 microM), and weakly inhibited by sulfate, phenylboronic, and phenyl
      arsonic acid (K(I)s of 14.15-30.85 mM). These data demonstrate that pathogenic,
      fungal beta-CAs may be targets for the development of antifungals that have a
      novel mechanism of action.

PMID- 18723349
TI  - Design, synthesis and preliminary biological evaluation of new hydroxamate
      histone deacetylase inhibitors as potential antileukemic agents.
AB  - This study concerns the synthesis of new histone deacetylase inhibitors (HDACi)
      characterized by a 1,4-benzodiazepine ring used as the cap, joined through an
      amide function or a triple bond as connection units, to a linear alkyl chain
      bearing the hydroxamate function as Zn2+-chelating group. Biological tests
      performed in human acute promyelocytic leukemia NB4 cells showed that new hybrids
      can induce histone H3/H4 acetylation, growth arrest, and also apoptosis. Notably,
      chiral compounds exhibit stereoselective activity.

PMID- 18723350
TI  - Development of novel tail-modified anandamide analogs.
AB  - To explore the hydrophobic groove subsite within the CB1 cannabinoid receptor we
      have designed and synthesized a group of tail-substituted anandamide analogs. Our
      design involves the introduction of aryl or heterocyclic ring as terminal
      substituents that are connected to the last cis-arachidonyl double bond through
      aliphatic chains of variable lengths. Our results indicate that there are strict
      stereochemical requirements for the interaction of such analogs with the CB1
      receptor. The optimal pharmacophore includes the phenyl, p-substituted phenyl, or
      3-furyl substituents attached to the cis-double bond through a four methylene
      chain.

PMID- 18723351
TI  - Conserved role of the Vsx genes supports a monophyletic origin for bilaterian
      visual systems.
AB  - BACKGROUND: Components of the genetic network specifying eye development are
      conserved from flies to humans, but homologies between individual neuronal cell
      types have been difficult to identify. In the vertebrate retina, the homeodomain
      containing transcription factor Chx10 is required for both progenitor cell
      proliferation and the development of the bipolar interneurons, which transmit
      visual signals from photoreceptors to ganglion cells. RESULTS: We show that dVsx1
      and dVsx2, the two Drosophila homologs of Chx10, play a conserved role in visual
      system development. DVSX1 is expressed in optic-lobe progenitor cells, and, in
      dVsx1 mutants, progenitor cell proliferation is defective, leading to
      hypocellularity. Subsequently, DVSX1 and DVSX2 are coexpressed in a subset of
      neurons in the medulla, including the transmedullary neurons that transmit visual
      information from photoreceptors to deeper layers of the visual system. In dVsx
      mutant adults, the optic lobe is reduced in size, and the medulla is small or
      absent. These results suggest that the progenitor cells and photoreceptor target
      neurons of the vertebrate retina and fly optic lobe are ancestrally related.
      Genetic and functional homology may extend to the neurons directly downstream of
      the bipolar and transmedullary neurons, the vertebrate ganglion cells and fly
      lobula projection neurons. Both cell types project to visual-processing centers
      in the brain, and both sequentially express the Math5/ATO and Brn3b/ACJ6
      transcription factors during their development. CONCLUSIONS: Our findings support
      a monophyletic origin for the bilaterian visual system in which the last common
      ancestor of flies and vertebrates already contained a primordial visual system
      with photoreceptors, interneurons, and projection neurons.

PMID- 18723352
TI  - Effect of lower limb muscle fatigue induced by high-level isometric contractions
      on postural maintenance and postural adjustments associated with bilateral
      forward-reach task.
AB  - This study tested the effect of lower limb muscle fatigue induced by series of
      high-level isometric contractions (IC) on postural adjustments and maintenance of
      erect posture. Subjects (N=7) displaced a bar (grasp-bar) forward with both hands
      at maximal velocity towards a target ("bilateral forward-reach" task, BFR),
      before and after a procedure designed to induce fatigue in dorsal leg muscles.
      This procedure included IC at 60% of maximum. Postural joint and grasp-bar
      motion, along with electrical activity of postural and focal muscles were
      recorded. Integrated electromyographical (EMG) activity per 20 ms period ranging
      from 400 ms before BFR onset (t0) to 400 ms after t0 was compared before and
      after the fatiguing procedure. This time-window included "anticipatory", "on
      line" and "corrective" postural adjustments, i.e. those postural adjustments
      occurring before (APAs), during (OPAs) and after (CPAs) BFR, respectively. In
      contrast to the literature, results showed that the fatiguing procedure had no
      effect on muscle excitation or timing in any of the recorded postural muscles,
      regardless of APA, OPA or CPA-related time-window. Therefore, the postural drive
      did not change with fatigue. Furthermore, the peak-to-peak motion at postural
      joints did not change. Postural maintenance was therefore not additionally
      challenged. These results are in line with the hypothesis that the effect of
      fatigue on postural adjustments is dependent on the adequacy between fatigued
      motor units (MUs) and MUs recruited during the postural adjustments. Increasing
      IC intensity during the fatiguing procedure might therefore not necessarily
      exacerbate the effect of fatigue on postural control highlighted during lower
      level IC.

PMID- 18723353
TI  - Cyclic diarylheptanoids from Myrica nana inhibiting nitric oxide release.
AB  - Investigation of the roots of Myrica nana afforded five new cyclic
      diarylheptanoids, myricananins A-E (1-5), two new artifacts of myricananins A and
      B (6-7), and four known compounds, 12-hydroxymyricanone (8), alnusonol (9),
      myricatomentogenin (10), and actinidione (11). The structures of these new
      compounds were established by detailed spectroscopic methods. The stereochemistry
      of compounds 1 and 2 were determined by single-crystal X-ray diffraction. In
      exception of compounds 2, 6 and 10, all the other compounds were examined for
      their inhibitory effects on nitric oxide production in lipopolysaccharides
      activated macrophages. Compounds 1, 3, 7, 8 and 9 inhibited the release of nitric
      oxide with IC(50) values of 45.32, 63.51, 52.81, 30.19 and 46.18muM,
      respectively. Furthermore, compound 1 was found to inhibit the expression of
      inducible nitric oxide synthase.

PMID- 18723354
TI  - Dual inhibition of monoamine oxidase B and antagonism of the adenosine A(2A)
      receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues.
AB  - The adenosine A(2A) receptor has emerged as an attractive target for the
      treatment of Parkinson's disease (PD). Evidence suggests that antagonists of the
      A(2A) receptor (A(2A) antagonists) may be neuroprotective and may help to
      alleviate the symptoms of PD. We have reported recently that several members of
      the (E)-8-styrylcaffeine class of A(2A) antagonists also are potent inhibitors of
      monoamine oxidase B (MAO-B). Since MAO-B inhibitors are known to possess anti
      parkinsonian properties, dual-target-directed drugs that block both MAO-B and
      A(2A) receptors may have enhanced value in the management of PD. In an attempt to
      explore this concept further we have prepared three additional classes of C-8
      substituted caffeinyl analogues. The 8-phenyl- and 8-benzylcaffeinyl analogues
      exhibited relatively weak MAO-B inhibition potencies while selected (E,E)-8-(4
      phenylbutadien-1-yl)caffeinyl analogues were found to be exceptionally potent
      reversible MAO-B inhibitors with enzyme-inhibitor dissociation constants (K(i)
      values) ranging from 17 to 149 nM. Furthermore, these (E,E)-8-(4-phenylbutadien-1
      yl)caffeines acted as potent A(2A) antagonists with K(i) values ranging from 59
      to 153 nM. We conclude that the (E,E)-8-(4-phenylbutadien-1-yl)caffeines are a
      promising candidate class of dual-acting compounds.

PMID- 18723355
TI  - Synthesis, biological active molecular design, and molecular docking study of
      novel deazaflavin-cholestane hybrid compounds.
AB  - Novel deazaflavin-cholestane hybrid compounds, 3',8'-disubstituted-5'
      deazacholest-2,4-dieno[2,3-g]pteridine-2',4'(3'H,8'H)-diones, have been
      synthesized by condensation reaction between 6-(monosubstituted amino)-pyrimidin
      2,4(1H,3H)-diones and 2-hydroxymethylenecholest-4-en-3-one in presence of p
      toluenesulfonic acid monohydrate and diphenyl ether. The antitumor activities
      against human tumor cell lines (CCRF-HSB-2 and KB cells) have been investigated
      in vitro, and many of these compounds showed promising antitumor activities.
      Furthermore, molecular docking study using LigandFit within the software package
      Discovery Studio 1.7 was done for lead optimization of these compounds as
      potential PTK inhibitors. In general, all of the synthesized steroid-hybrid
      compounds showed good binding affinities into PTK (PDB code: 1t46).

PMID- 18723356
TI  - Synthesis and pharmacological evaluation of bis-3-(3,4-dichlorophenyl)acrylamide
      derivatives as glycogen phosphorylase inhibitors.
AB  - During our research using a high-throughput screening system for discovery of a
      new class of human liver glycogen phosphorylase a (hLGPa) inhibitors, a series of
      3-(3,4-dichlorophenyl)acrylamide derivatives were synthesized, and their
      inhibitory activities toward hLGPa were evaluated. Among the derivatives,
      (2E,2'E)-N,N'-pentane-1,5-diylbis[3-(3,4-dichlorophenyl)acrylamide] (6c)
      inhibited hLGPa with an IC(50) value of 0.023 microM. An X-ray crystallographic
      study of the enzyme-6c complex showed that the inhibitor is bound at the dimer
      interface site, where the 3,4-dichlorophenyl moiety interacts hydrophobically
      with the enzyme.

PMID- 18723357
TI  - Development and biological evaluation of C(60) fulleropyrrolidine-thalidomide
      dyad as a new anti-inflammation agent.
AB  - Research studies in the field of C(60) fullerene derivatives have significantly
      increased due to the broad range of biological activities that were found for
      these compounds. We designed and prepared a new C(60) fullerene hybrid bearing
      thalidomide as a potential double-action anti-inflammatory agent, capable of
      simultaneous inhibition of LPS-induced NO and TNF-alpha production. The C(60)
      fulleropyrrolidine-thalidomide dyad, CLT, was an effective agent to suppress the
      release of NO and TNF-alpha by the LPS-stimulated macrophages RAW 264.7. Ten
      micromolars of CLT effectively inhibited LPS-induced NO and TNF-alpha production
      by 47.3+/-4.2% and 70.2+/-4% with respected to the control, respectively.
      Furthermore, preliminary biochemical investigation revealed that CLT was a potent
      agent to suppress both LPS-induced intracellular ROS production and iNOS
      expression, and CLT also inhibited the phosphorylation of ERK which is an
      important protein kinase involved in the activation of TNF-alpha synthesis in LPS
      activated macrophages. We believed that the studies herein would hold promise for
      future development of a new generation of potent anti-inflammatory agents.

PMID- 18723358
TI  - Synthesis of highly selective fluorescent peptide probes for metal ions: tuning
      selective metal monitoring with secondary structure.
AB  - Metal selective fluorescent peptide probes (dansyl-Cys-X-Gly-His-X-Gly-Glu-NH2, X
      = Pro or Gly) were developed by synthesizing peptides containing His, Cys, and
      Glu residues with Pro-Gly sequence to stabilize a turn structure and Gly-Gly
      sequence to adopt a random coil. The probe containing two Gly-Gly sequences
      exhibited marked selectivity only for Cu2+ over 13 metal ions including
      competitive transition and Group I and II metal ions under physiological buffer
      condition. In contrast, the probe containing double Pro-Gly sequences showed high
      selectivity for Zn2+. The peptide probe containing one Pro-Gly sequence exhibited
      selectivity for Zn2+ and Cu2+. CD spectra indicated that the secondary structure
      of the probes played an important role in the selective metal monitoring and a
      pre-organized secondary structure is not required for the selective detection of
      Cu2+ ion, but is required for the detection of Zn2+. We investigated and
      characterized the binding affinity, binding stoichiometry, reversibility, and pH
      sensitivity of the peptide probes.

PMID- 18723359
TI  - Comparative docking studies of labdane-type diterpenes with forskolin at the
      active site of adenylyl cyclase.
AB  - Diterpen labd-13(E)-ene-8a,15-diol (1) is a natural product found to possess
      potential cytotoxic and cytostatic effects against human cancer cell lines.
      Adenylyl cyclases (ACs) are promising pharmacological targets for treating heart
      failure, cancer, and psychosis. It has been demonstrated that forskolin is a
      potent adenylyl cyclase activator. Labdane 1 belongs to same family as forskolin.
      Its conformational properties are explored using a combination of 1D, 2D NMR
      spectroscopy, and molecular modeling techniques. The derived low energy
      conformers are subjected to docking calculations aiming to reveal similarities
      and differences in the binding mode between 1 and forskolin. Additionally,
      docking calculations performed on the 1alpha,9alpha-OH and 1alpha-OH derivatives
      of 1 suggest major contribution of 1alpha position in increasing binding
      affinity. This information may be of paramount importance to medicinal chemists
      who are interested in the synthesis of proposed analogs and test the docking
      results through in vitro experiments.

PMID- 18723360
TI  - Novel iron complexes bearing N6-substituted adenosine derivatives: synthesis,
      magnetic, 57Fe Mossbauer, DFT, and in vitro cytotoxicity studies.
AB  - Iron complexes (1-7) involving N6-benzyladenosine derivatives of the predominant
      composition [Fe(L(n))Cl(3)].H(2)O {where L(1)=N6-(2-fluorobenzyl)adenosine (1),
      L(2)=N6-(4-fluorobenzyl)adenosine (2), L(3)=N6-(2-trifluoromethylbenzyl)adenosine
      (3), L(4)=N6-(3-trifluoromethylbenzyl)adenosine (4), L(5)=N6-(4
      trifluoromethylbenzyl)adenosine (5), L(6)=N6-(4-trifluoromethoxybenzyl)adenosine
      (6), and L(7)=N6-(4-chlorobenzyl)adenosine (7)} have been synthesized. The
      compounds have been characterized by elemental analysis, variable-temperature and
      in-field 57Fe Mossbauer, ES+ MS, FTIR, 1H and 13C NMR spectroscopies,
      magnetochemical and conductivity measurements, thermal (TGA/DSC/DTA) analyses,
      and DFT calculations. It has been found that the organic molecule is coordinated
      to iron via N7 atom of the appropriate adenosine derivative and the products are
      represented by mixtures of complexes with various iron oxidation (Fe(III)/Fe(II))
      and spin states (S=5/2, 4/2, 3/2, 2/2) and geometries (tetrahedral or trigonal
      bipyramidal). It is caused by the fact that partial redox processes proceed
      during the reactions due to the presence of a ribose moiety, which is oxidized to
      the corresponding 5'-ribotic acid, and simultaneously, a portion of Fe(III)
      cations is reduced to Fe(II) ones. Moreover, a significant effect of crystal
      water molecules on stereochemistry, and hence, on magnetic and spectral
      properties of the prepared complexes has been found. The compounds have been
      tested for their in vitro cytotoxicity against the following human cancer cell
      lines: malignant melanoma (G-361), osteogenic sarcoma (HOS), chronic myelogenous
      leukemia (K-562), and breast adenocarcinoma (MCF-7). The most important results
      have been obtained for complex 2 with IC(50) values 8-16 microM against HOS, K
      562, and MCF-7 cell lines, and for complex 6 with IC(50) value 4 microM against
      MCF-7 cell line.

PMID- 18723361
TI  - Characterization of human kidney stones using micro-PIXE and RBS: a comparative
      study between two different populations.
AB  - The micro-PIXE and RBS techniques are used to investigate the matrix as well as
      the trace elemental composition of calcium-rich human tissues on a microscopic
      scale. This paper deals with the spatial distribution of trace metals in hard
      human tissues such as kidney stone concretions, undertaken at the nuclear
      microprobe (NMP) facility. Relevant information about ion beam techniques used
      for material characterization will be discussed. Mapping correlation between
      different trace metals to extract information related to micro-regions
      composition will be illustrated with an application using proton energies of 1.5
      and 3.0 MeV and applied to a comparative study for human kidney stone concretions
      nucleation region analysis from two different population groups (Sudan and South
      Africa).

PMID- 18723362
TI  - AtERF38 (At2g35700), an AP2/ERF family transcription factor gene from Arabidopsis
      thaliana, is expressed in specific cell types of roots, stems and seeds that
      undergo suberization.
AB  - An inverse genetic approach was used to gain insight into the role of AP2/ERF
      type transcription factors genes during plant development in Arabidopsis
      thaliana. Here we show that the expression pattern of AtERF38, which is, among
      the organs tested, more intensively expressed in mature siliques and floral
      stems, is closely associated with tissues that undergo secondary cell wall
      modifications. Firstly, public microarray data sets analysis indicates that
      AtERF38 is coregulated with several genes involved in secondary wall thickening.
      Secondly, this was experimentally confirmed in different types of cells
      expressing a Pro(AtERF38)::GUS fusion: histochemical analysis revealed strong and
      specific GUS activity in outer integument cells of mature seeds, endodermal cells
      of the roots in the primary developmental stage and some sclerified cells of
      mature inflorescence stems. All of these cells are known or shown here to be
      characterized by a reinforced wall. The latter, which have not been well
      characterized to date in Arabidopsis and may be suberized, could benefit of the
      use of AtERF38 as a specific marker. We were not able to detect any phenotype in
      an insertion line in which ectopic expression of AtERF38 is caused by the
      insertion of a T-DNA in its promoter. Nevertheless, AtERF28 may be considered as
      a candidate regulator of secondary wall metabolism in particular cell types that
      are not reinforced by the typical deposition of lignin and cellulose, but that
      have at least in common accumulation of suberin-like lipid polyesters in their
      walls.

PMID- 18723363
TI  - Orbital emphysema - the need for surgical intervention.
AB  - INTRODUCTION: Orbital emphysema is a recognised complication of fractures of the
      orbit and only rarely poses a threat to vision. PATIENTS AND METHODS: We present
      three patients with threatened vision secondary to orbital emphysema that
      required an immediate surgical decompression. RESULTS: Visual function was
      preserved in all three patients. CONCLUSION: Clinical awareness of pneumo
      orbitism is vital as immediate orbital decompression may be necessary to preserve
      visual function.

PMID- 18723364
TI  - Patency rate of the internal thoracic artery to the left anterior descending
      artery bypass is reduced by competitive flow from the concomitant saphenous vein
      graft in the left coronary artery.
AB  - OBJECTIVE: In coronary artery bypass grafting (CABG), insufficient bypass flow
      can be a cause of occlusion or string sign of the internal thoracic artery (ITA)
      graft. A patent saphenous vein (SV) graft from the ascending aorta can reduce the
      blood flow through the ITA graft, and may affect its long-term patency. In the
      present study, we examined the impact of the patent SV graft to the left coronary
      artery on the long-term patency of the ITA to left anterior descending (LAD)
      artery bypass. METHODS: We reviewed the coronary angiograms of 313 patients who
      had two bypasses to the left coronary artery including 1 in situ ITA to LAD graft
      between March 1986 and December 2006. Patients who had occlusion of either bypass
      grafts to the left coronary artery in the early angiography, were excluded. In 64
      patients (20.4%), bilateral ITAs were individually anastomosed to the LAD and the
      second target branch in the left coronary artery (BITA group), while 249 patients
      (79.6%) had the ITA to LAD bypass and the SV graft to the second target branch in
      the left coronary artery (ITA/SV group). The mean follow-up period was 6.8+/-4.9
      years. RESULTS: The cumulative patency rate of ITA-LAD bypasses at 10 years was
      100% in the BITA group and 81.4% in the ITA/SV group. The ITA to LAD bypass was
      occluded in 14 (5.6%) patients of the ITA/SV group. In the ITA/SV group, the
      cumulative graft patency rate of the ITA to LAD bypass in patients who had severe
      (> or =76%) native coronary stenosis between the two anastomotic sites was 98.6%
      at 5 years, and was significantly higher than that of 82.3% in patients without
      severe stenosis (p<0.0001). CONCLUSIONS: Long-term patency of the ITA-LAD bypass
      was affected by the presence of the patent SV graft to the left coronary artery,
      particularly when the native coronary stenosis between the two anastomotic sites
      was not severe. Competitive flow from SV graft could play an important role in
      occlusion of the in-situ arterial graft.

PMID- 18723366
TI  - Assessing genotypic variability of cowpea (Vigna unguiculata [L.] Walp.) to
      current and projected ultraviolet-B radiation.
AB  - The current and projected terrestrial ultraviolet-B (UV-B) radiation affects
      growth and reproductive potential of many crops. Cowpea (Vigna unguiculata [L.]
      Walp.), mostly grown in tropical and sub-tropical regions may already be
      experiencing critical doses of UV-B radiation due to a thinner ozone column in
      those regions. Better understanding of genotypic variability to UV-B radiation is
      a prerequisite in developing genotypes tolerant to current and projected changes
      in UV-B radiation. An experiment was conducted in sunlit, controlled environment
      chambers to evaluate the sensitivity of cowpea genotypes to a range of UV-B
      radiation levels. Six cowpea genotypes [Prima, California Blackeye (CB)-5, CB-27,
      CB-46, Mississippi Pinkeye (MPE) and UCR-193], representing origin of different
      geographical locations, were grown at 30/22 degrees C day/night temperature from
      seeding to maturity. Four biologically effective ultraviolet-B radiation
      treatments of 0 (control), 5, 10, and 15 kJ m(-2)d(-1) were imposed from eight
      days after emergence to maturity. Significant genotypic variability was observed
      for UV-B responsiveness of eighteen plant attributes measured. The magnitude of
      the sensitivity to UV-B radiation also varied among cowpea genotypes. Plants from
      all genotypes grown in elevated UV-B radiation were significantly shorter in stem
      and flower lengths and exhibited lower seed yields compared to the plants grown
      under control conditions. Most of the vegetative parameters, in general, showed a
      positive response to UV-B, whereas the reproductive parameters exhibited a
      negative response showing the importance of reproductive characters in
      determining tolerance of cultivars to UV-B radiation. However, all cultivars,
      except MPE, behaved negatively to UV-B when a combined response index was derived
      across parameters and UV-B levels. Based on the combined total stress response
      index (C-TSRI) calculated as sum of individual vegetative, physiological and
      reproductive component responses over the UV-B treatments, the genotypes were
      classified as tolerant (MPE), intermediate (CB-5, CB-46 and UCR-193) and
      sensitive (CB-27 and Prima) to UV-B radiation. The differences in sensitivity
      among the cowpea genotypes emphasize the need for selecting or developing
      genotypes with tolerance to current and projected UV-B radiation.

PMID- 18723367
TI  - Multidimensional geriatric assessment in treatment decision in elderly cancer
      patients: 6-year experience in an outpatient geriatric oncology service.
AB  - This prospective cohort study of consecutive elderly cancer patients was
      undertaken to evaluate the role of the multidimensional geriatric assessment
      (MGA) as an aid in treatment decision-making. A total of 571 cancer patients
      (aged > or =70) were enrolled during 6-year (1999-2005). All underwent MGA as
      part of the first evaluation. In multivariate analysis, the probability of
      receiving active, instead of palliative, treatment was negatively associated with
      increasing age (odds ratio=0.69 every 5 years, p=0.005), living alone (OR=0.54,
      p=0.031), dependence in activities of daily living (ADL score >0, OR=0.41,
      p=0.003) and a low body-mass index (BMI) (OR=0.51, p=0.061); while a positive
      association emerged for instrumental activities of daily living (IADL) score
      (OR=1.12 per point, p=0.019). Our data suggest that MGA, in addition to age, is a
      useful tool in clinical practice for deciding cancer treatment in elderly
      patients, with a major independent role played by living alone, ADL, IADL and
      BMI.

PMID- 18723368
TI  - Optimizing treatment for men with advanced prostate cancer: expert
      recommendations and the multidisciplinary approach.
AB  - A multidisciplinary panel of 20 international experts, including urologists,
      radiation oncologists, and medical oncologists, convened during the Advanced
      Prostate Cancer Multidisciplinary Team meeting in Rome, Italy, in January 2007,
      to discuss the multidisciplinary team approach and current patterns of care for
      patients with hormone-refractory prostate cancer (HRPC). During the meeting, the
      experts discussed several definitions currently used in prostate cancer
      management, including those for senior adult patients. In addition, the panel
      reviewed a series of patient case studies in order to provide feedback on current
      treatment practices and to identify possible strategies for best practice. It was
      stressed that treatment decisions for senior adult patients should not be based
      solely on patient age. Additionally, although historically treatment decisions
      for advanced prostate cancer have focused on palliative care, given the survival
      benefit associated with docetaxel-based chemotherapy across patient subgroups,
      more men are likely to be offered chemotherapy for advanced-stage disease in the
      future.

PMID- 18723369
TI  - Palonosetron plus dexamethasone effectively prevents acute and delayed
      chemotherapy-induced nausea and vomiting following highly or moderately
      emetogenic chemotherapy in pre-treated patients who have failed to respond to a
      previous antiemetic treatment: comparison between elderly and non-elderly patient
      response.
AB  - Aim of the present phase II non-randomized study was to verify whether
      palonosetron might be able to prevent acute and especially delayed CINV for
      either HEC or MEC, starting from the second chemotherapy cycle, in patients who
      had failed to respond to a different antiemetic 5-HT(3) antagonist during the
      first cycle. Stratification factor was age <65 years vs. > or =65 years of
      patients included. Forty-seven cancer patients (23 elderly and 24 non-elderly)
      scheduled to receive HEC or MEC regimens who had experienced CINV grade 3-4
      during the first chemotherapy course and for whom the same course of chemotherapy
      regimen was further scheduled were enrolled. Complete response (CR) and complete
      control (CC) rates for the acute, delayed and overall phases of CINV were not
      significantly different between elderly and non-elderly patients. Palonosetron
      was safe: only grade 1-2 toxicities were observed with a peak of 12.9% for
      asthenia with no significant difference between elderly and non-elderly patients.
      In conclusion, single dose palonosetron (250 microg) should be considered a safe
      and effective second generation 5-HT(3) antagonist in the prevention of nausea
      and vomiting induced by HEC or MEC, irrespective of patients' age.

PMID- 18723370
TI  - Prostate cancer. Multidisciplinary approach: a key to success.
AB  - Diagnosis and treatment of prostate cancer has improved in the last few years, in
      part due to a multidisciplinary approach between urologists, oncologists,
      radiotherapists, radiologists, pathologists, basic and translational researchers
      for a successful management. The TAX 327 study is the paradigm of a smooth
      communication between expert physicians that led to the approval of docetaxel in
      metastatic hormone-resistant prostate cancer (HRPC). Survival benefit with
      docetaxel in HRPC was confirmed in an updated survival analysis reported this
      year. A nomogram to predict survival in metastatic HRPC treated with chemotherapy
      was established based on the TAX 327 study. Unfortunately in early prostate
      cancer, some of the phase III clinical trials with chemotherapy had to be closed
      due to lack of sufficient accrual, due to, at least in part, an unsuccessful
      collaboration between urologists, medical oncologists and radiotherapists. In
      earlier phases of prostate cancer, a successful multidisciplinary approach has
      led to important advances in genomics, biomarkers and imaging techniques that
      have created big excitement for future improvements in the management of prostate
      cancer. An example is the validation of novel molecular diagnosis tests such as
      PCA3 or TMPRSS2 - ETS in urinary samples. Importantly, we should not forget that
      the key for a successful future development in the management of prostate cancer
      will require the expertise of all disciplines to provide optimal care.

PMID- 18723371
TI  - Treatment with an Interleukin 1 beta antibody improves glycemic control in diet
      induced obesity.
AB  - The proinflammatory cytokine Interleukin 1 beta (IL-1beta) is elevated in obese
      individuals and rodents and it is implicated in impaired insulin secretion,
      decreased cell proliferation and apoptosis of pancreatic beta cells. In this
      study we describe the therapeutic effects by an IL-1beta antibody to improve
      glucose control in hyperglycemic mice with diet-induced obesity. After 13 weeks
      of treatment the IL-1beta antibody treated group showed reduced glycated
      hemoglobin (( *)P=0.049), reduced serum levels of proinsulin (( *)P=0.015),
      reduced levels of insulin and smaller islet size (( *)P=1.65E-13) relative to the
      control antibody treated group. Neutralization of IL-1beta also significantly
      reduced serum amyloid A (SAA) which is an indicator of inflammation-induced acute
      phase response (( *)P=0.024). While there was no improvement of obesity, a
      significant improvement of glycemic control and of beta cell function is achieved
      by this pharmacological treatment which may slow/prevent disease progression in
      Type 2 Diabetes.

PMID- 18723372
TI  - Inhibition of lipopolysaccharide-induced nitric oxide synthesis by nicotine
      through S6K1-p42/44 MAPK pathway and STAT3 (Ser 727) phosphorylation in Raw 264.7
      cells.
AB  - Lipopolysaccharide (LPS) has been known to produce inflammatory modulators such
      as tumor necrosis factor alpha (TNF-alpha) or nitric oxide (NO). In this study,
      we examined the effects of nicotine on LPS enhanced NO synthesis and inducible
      nitric oxide synthase (iNOS) expression in macrophages. LPS-induced NO synthesis
      and iNOS expression were significantly decreased by nicotine. To investigate the
      signaling mechanism of nicotine induced suppression of NO synthesis and iNOS
      expression induced by LPS, we focused on the possible roles of p42/44 MAPK, S6K1,
      and signal transducers and activators of transcription 3 (STAT3) signaling. LPS
      is known to activate p42/44 MAPK and S6K1, which in turn activates STAT3 to
      induce inflammatory regulators. Pretreatment of cells with nicotine blocked LPS
      induced p42/44 MAPK and S6K1 as well as iNOS promoter activity. Furthermore, we
      found that LPS-induced phosphorylation of STAT3 at serine 727 is mediated by S6K1
      p42/44 MAPK pathway, and this STAT3 phosphorylation was also blocked by nicotine.
      We also found that downregulation of STAT3 using STAT3 siRNA resulted in
      suppression of the NO synthesis and iNOS expression. Taken together, our results
      suggest that nicotine inhibits LPS-induced NO synthesis through suppression of
      S6K1-p42/44 MAPK pathway and phosphorylation of STAT3 in Raw 264.7 cells.

PMID- 18723373
TI  - Reflections on the future of women's health research in a comparative context why
      more than sex and gender matters.

PMID- 18723375
TI  - A question of intention in motor imagery.
AB  - We examined the question-is the intention of completing a simulated motor action
      the same as the intention used in processing overt actions? Participants used
      motor imagery to estimate distance reachability in two conditions: Imagery-Only
      (IO) and Imagery-Execution (IE). With IO (red target) only a verbal estimate
      using imagery was given. With IE (green target) participants knew that they would
      actually reach after giving a verbal estimate and be judged on accuracy. After
      measuring actual maximum reach, used for the comparison, imagery targets were
      randomly presented across peripersonal- (within reach) and extrapersonal (beyond
      reach) space. Results indicated no difference in overall accuracy by condition,
      however, there was a significant distinction by space; participants were more
      accurate in peripersonal space. Although more research is needed, these findings
      support an increasing body of evidence suggesting that the neurocognitive
      processes (in this case, intention) driving motor imagery and overt actions are
      similar.

PMID- 18723374
TI  - Self-assessed physical function levels of women with fibromyalgia: a national
      survey.
AB  - OBJECTIVE: We sought to determine the self-reported physical function level of
      women with fibromyalgia (FM). METHODS: We performed a secondary analysis using
      data from an Internet-based survey posted on the National Fibromyalgia
      Association website. Data used for this study included women (n = 1,735) aged 31
      78 years who reported being diagnosed with FM. RESULTS: More than 25% of women
      reported having difficulty taking care of personal needs and bathing, and >60%
      reported difficulty doing light household tasks, going up/down 1 flight of
      stairs, walking (1/2) mile, and lifting or carrying 10 lbs. More than 90% of
      women reported having difficulty doing heavy household tasks, lifting or carrying
      25 lbs, and doing strenuous activities. Women with lower functional ability
      reported higher levels of fatigue, pain, spasticity, depression, restless legs,
      balance problems, dizziness, fear of falling, and bladder problems. CONCLUSIONS:
      The average woman in this sample reported having less functional ability related
      to activities of daily living and instrumental activities of daily living than
      the average community-dwelling woman in her 80s. Several symptoms/conditions were
      found to be associated with functional limitation in women with FM. Targeting
      these-singly or in clusters-may potentially be important in terms of future
      interventions.

PMID- 18723376
TI  - Frequency and patterns of MRI abnormalities due to status epilepticus.
AB  - BACKGROUND: MRI changes due to status epilepticus (SE) often suggest a
      combination of cytotoxic and vasogenic edema, but it is unclear why only certain
      patients have MRI changes. OBJECTIVES: To determine the frequency of MRI changes
      due to SE and the associated patient characteristics. METHODS: We reviewed
      records for demographics, medical history, and MRI changes attributable to
      seizures of all patients admitted to Brigham and Women's Hospital or
      Massachusetts General Hospital for SE from 1/1999 to 7/2003 and who had MRI
      during admission. RESULTS: Ten (11.6%) of the eighty-six patients identified had
      MRI abnormalities likely due to seizures. Four, two with pre-existing epilepsy
      and two with extratemporal structural lesions, had focally increased signal on T2
      and diffusion-weighted imaging (DWI) in the hippocampus ipsilateral to the
      seizure focus. One, with elevated levels of clozapine, had increased signal on T2
      weighted images and variably restricted diffusion in the splenium. Five had gyral
      distribution of restricted diffusion and increased signal on T2 weighted images;
      they had complex medical comorbidities and possible hypoperfusion or hypoxia
      associated with SE. CONCLUSIONS: Among patients with SE who had MRI changes,
      those with previous epilepsy or extratemporal structural lesions showed increased
      diffusion in the hippocampus and may have selective hippocampal vulnerability to
      seizure-induced hyperexcitability. Patients with hyperintense signal in the
      cortical gray matter had episodes of possible hypoperfusion or hypoxia.

PMID- 18723377
TI  - Current concepts in the pathogenesis of osteoarthritis.

PMID- 18723378
TI  - Spin-diffusion couples proton relaxation rates for proteins in exchange with a
      membrane interface.
AB  - Changes in nuclear spin-lattice relaxation rates that are induced by a freely
      diffusing paramagnetic relaxation agent are examined for a protein in solution
      and compared to the case where the protein binds to a membrane. In the solution
      case, the intramolecular cross-relaxation rates are modest and large differences
      are observed in the oxygen induced protein-proton relaxation rates. In the case
      where a dynamic equilibrium between solution and membrane-bound environments is
      established, the intramolecular (1)H cross-relaxation rates for the protein
      protons increase dramatically because of the slow reorientational motion in the
      membrane-bound environment. As a consequence, all protein protons relax with
      nearly the same spin-lattice relaxation rate constants when bound to the
      membrane, and site specific relaxation effects of the diffusing paramagnet are
      suppressed. Slowly reorienting sites or rotationally immobilized sites sampled by
      observable molecules in vivo will demonstrate similar relaxation leveling
      effects.

PMID- 18723379
TI  - Differences in epidemiological and clinical characteristics between various types
      of Duane retraction syndrome in 331 patients.
AB  - PURPOSE: To determine the differences in various epidemiologic and clinical
      characteristics among types I, II, and III of unilateral Duane syndrome and
      between unilateral and bilateral Duane syndrome. METHODS: A retrospective chart
      review of 331 patients with the Duane syndrome (291 unilateral and 40 bilateral)
      was performed. Various characteristics studied included sex, age at presentation,
      laterality, manifest primary position horizontal deviation, upshoot and
      downshoot, amblyopia, and associated ocular and systemic abnormalities. RESULTS:
      Unilateral types I and III Duane syndrome were more common in the left eye and in
      female patients, whereas type II had no such predilection. The mean age at
      presentation was significantly greater in type III patients. Type I patients had
      an almost-equal frequency of esotropia and exotropia, type II had exotropia, and
      type III had exotropia more commonly than esotropia. The upshoots and downshoots
      were more common in types II and III. There was no difference in amblyopia among
      various types of Duane syndrome. Associated ocular abnormalities were more common
      in types I and III, and systemic abnormalities were more common in type I. A
      manifest primary position horizontal deviation was more common in bilateral Duane
      syndrome. Exotropia was more common in unilateral cases, whereas esotropia was
      more common in bilateral cases. CONCLUSION: Unilateral types I, II, and III Duane
      syndrome differ in the mean age at presentation, primary position horizontal
      deviation, upshoot and downshoot, and associated ocular and systemic
      abnormalities. Bilateral Duane syndrome differs from the unilateral only in the
      primary position horizontal deviation.

PMID- 18723380
TI  - Mitochondrial deoxyribonucleotide pools in deoxyguanosine kinase deficiency.
AB  - Mutated deoxyguanosine kinase (dGK), which catalyses the first step of the
      mitochondrial deoxypurine salvage pathway, accounts for a hepatocerebral variant
      of mitochondrial DNA (mtDNA) depletion syndromes. In order to elucidate the
      pathogenic mechanism of dGK deficiency, mitochondrial and cytoplasmic
      deoxyribonucleoside triphosphate (dNTP) pools in cycling and quiescent
      fibroblasts from a dGK deficient patient were measured. The mitochondrial dNTP
      pools were found to be imbalanced, mainly in quiescent cells due to decreased
      dGTP while mtDNA content and mitochondrial respiratory chain activities were
      concomitantly decreased. Supplementation of deoxyguanosine and deoxyadenosine
      normalized mitochondrial dNTP pools, mtDNA content and partially restored the MRC
      function. It is suggested that the cytoplasmic deoxycytine kinase supplemented
      with external substrates may compensate for the deficient dGK.

PMID- 18723381
TI  - Hepatitis B vaccine: a seven-year study of adherence to the immunization
      guidelines and efficacy in HIV-1-positive adults.
AB  - BACKGROUND: Vaccination against hepatitis B virus (HBV) has been recommended for
      all high-risk adults since 1982. Since the advent of highly active antiretroviral
      therapy, few studies have examined adherence to the Infectious Diseases Society
      of America (IDSA) and Advisory Committee on Immunization Practices (ACIP)
      guidelines for hepatitis B vaccination in persons infected with HIV. METHODS:
      This was a seven-year retrospective, cross-sectional analysis of HBV vaccination
      practices in HIV-1-positive adults treated in an urban ambulatory care center.
      Compliance with screening, hepatitis B vaccination recommendations, and response
      to vaccination were assessed. RESULTS: Of the 1601 charts reviewed, 717 persons
      were eligible for vaccination against hepatitis B. Of these patients, 503
      received at least one dose of vaccine, but only 356 patients completed the three
      dose series. Vaccine response was associated with CD4 count (p=0.006) and viral
      load (p=0.001) at the time of the first dose. However, development of hepatitis B
      surface antibody was seen at all CD4 counts and viral loads. The multivariate
      analysis showed only the HIV viral load was predictive of immunologic response.
      Twenty of the vaccine-eligible patients who did not receive vaccination were
      infected with HBV during the study period. No vaccinated persons contracted
      hepatitis B. CONCLUSION: Failure to implement these guidelines represents a
      missed opportunity to prevent disease. In our study, HIV viral load was better
      than CD4 count as a predictor of response to the HBV vaccination. However,
      neither low CD4 count nor high HIV viral load should be used as justification to
      delay vaccination of high-risk persons.

PMID- 18723382
TI  - Injuries due to sharp trauma detected by post-mortem multislice computed
      tomography (MSCT): a feasibility study.
AB  - Modern cross-sectional imaging techniques are being increasingly implemented in
      forensic pathology. In order to assess the practicability of such a method,
      namely post-mortem multislice computed tomography (MSCT) in cases of fatal cut
      and stab injuries, 12 corpses underwent such an examination prior to forensic
      autopsy. The questions regarding detection of foreign bodies, wound channels,
      skeletal and organ injuries, as well as the cause of death were addressed at MSCT
      and autopsy. The results of the two techniques revealed that post-mortem MSCT a
      useful tool in the assessment of such injuries.

PMID- 18723383
TI  - Population data for 15 autosomal STRs loci and 12 Y chromosome STRs loci in a
      population sample from the Sardinia island (Italy).
AB  - One hundred twenty-five unrelated individuals (69 females and 56 males) from
      Sassari (Northern Sardinia) and Orgosolo (Central Sardinia) were typed for 15
      STRs loci. The 56 males were typed for 12 Y chromosome STRs loci too. Frequency
      distribution is described.

PMID- 18723385
TI  - A simulation and estimation framework for intracellular dynamics and trafficking
      in video-microscopy and fluorescence imagery.
AB  - Image sequence analysis in video-microscopy has now gained importance since
      molecular biology is presently having a profound impact on the way research is
      being conducted in medicine. However, image processing techniques that are
      currently used for modeling intracellular dynamics, are still relatively crude
      and yield imprecise results. Indeed, complex interactions between a large number
      of small moving particles in a complex scene cannot be easily modeled, limiting
      the performance of object detection and tracking algorithms. This motivates our
      present research effort which is to develop a general estimation/simulation
      framework able to produce image sequences showing small moving spots in
      interaction, with variable velocities, and corresponding to intracellular
      dynamics and trafficking in biology. It is now well established that spot/object
      trajectories can play a role in the analysis of living cell dynamics and
      simulating realistic image sequences is then of major importance. We demonstrate
      the potential of the proposed simulation/estimation framework in experiments, and
      show that this approach can also be used to evaluate the performance of object
      detection/tracking algorithms in video-microscopy and fluorescence imagery.

PMID- 18723384
TI  - Pallidonigral TDP-43 pathology in Perry syndrome.
AB  - OBJECTIVE: Autosomal dominant parkinsonism, hypoventilation, depression and
      severe weight loss (Perry syndrome) is an early-onset rapidly progressive
      disease. At autopsy, previous studies have found severe neuronal loss in the
      substantia nigra without Lewy bodies. Transactive response DNA-binding protein of
      43 kDa (TDP-43) has recently been identified as a major ubiquitinated constituent
      of neuronal and glial inclusions in frontotemporal lobar degeneration with
      ubiquitin-positive inclusions and in amyotrophic lateral sclerosis. This study
      reports clinical, genetic and neuropathologic investigations of Perry syndrome.
      METHODS: Clinical data and autopsy brain tissue samples were collected from eight
      patients from four genealogically unrelated kindreds with Perry syndrome. Brain
      tissue was studied with immunohistochemistry and biochemistry for TDP-43.
      Patients were screened for mutations in the progranulin (GRN) and TDP-43 (TARDBP)
      genes. RESULTS: The mean age at onset was 47 years (range 40-56), and the mean
      age at death was 52 years (range 44-64). In all patients, we identified TDP-43
      positive neuronal inclusions, dystrophic neurites and axonal spheroids in a
      predominantly pallidonigral distribution, and we demonstrated changes in
      solubility and electrophoretic mobility of TDP-43 in brain tissue. The inclusions
      were highly pleomorphic and predominated in the extrapyramidal system, sparing
      the cortex, hippocampus and motor neurons. There were no mutations in GRN or
      TARDBP. INTERPRETATION: Perry syndrome displays unique TDP-43 pathology that is
      selective for the extrapyramidal system and spares the neocortex and motor
      neurons.

PMID- 18723386
TI  - Fitting the post-keratoplasty cornea with hydrogel lenses.
AB  - PURPOSE: We report two cases who have undergone penetrating keratoplasty (three
      eyes total), and who were fitted with hydrogel lenses. METHODS: In the first
      case, a 28-year-old male presented with an interest in contact lens fitting. He
      had undergone corneal transplantation in both eyes, about 5 years ago. After
      topographies and trial fitting were performed, it was decided to be fitted with
      reverse geometry hydrogel lenses, due to the globular geometry of the cornea, the
      resultant instability of RGPs, and personal preference. In the second case, a 26
      year-old female who had also penetrating keratoplasty was fitted with a hydrogel
      toric lens of high cylinder in the right eye. RESULTS: The final hydrogel lenses
      for the first subject incorporated a custom tricurve design, in which the second
      curve was steeper than the base curve and the third curve flatter than the second
      but still steeper than the first. Visual acuity was 6/7.5 RE and a mediocre 6/15
      LE (OU 6/7.5). The second subject achieved 6/4.5 acuity RE with the high cylinder
      hydrogel toric lens. CONCLUSIONS: In corneas exhibiting extreme protrusion, such
      as keratoglobus and some cases after penetrating keratoplasty, curvatures are so
      extreme and the cornea so globular leading to specific fitting options: sclerals,
      small diameter RGPs and reverse geometry hydrogel lenses, in order to improve
      lens and optical stability. In selected cases such as the above, large diameter
      inverse geometry RGP may be fitted only if the eyelid shape and tension permits
      so. The first case demonstrates that the option of hydrogel lenses is viable when
      the patient has no interest in RGPs and in certain cases can improve vision to
      satisfactory levels. In other cases, graft toricity might be so high that the
      practitioner will need to employ hydrogel torics with large amounts of cylinder
      in order to correct vision. In such cases, the patient should be closely
      monitored in order to avoid complications from hypoxia.

PMID- 18723387
TI  - The expression of NF-kappaB, Ki-67 and MMP-9 in CCOT, DGCT and GCOC.
AB  - Calcifying odontogenic cysts (COCs) represent a group of rare odontogenic lesions
      with a diversity of clinicopathological and behavioral features. According to the
      WHO classification of head and neck tumors in 2005, COC has been divided into
      calcifying cystic odontogenic tumor (CCOT), dentinogenic ghost cell tumor (DGCT)
      and ghost cell odontogenic carcinoma (GCOC). With few reports available on its
      immunohistochemical profile, this study investigated the histopathological
      features and the expression of nuclear factor kappaB (NF-kappaB), Ki-67 and
      matrix metalloproteinase-9 (MMP-9) in CCOT, DGCT and GCOC. According to the WHO
      classification of head and neck tumors in 2005, 26 cases of the so-called COC
      were diagnosed as CCOT (n=14), DGCT (n=7) and GCOC (n=5), respectively. The
      specimens of 26 COCs and 10 classic ameloblastomas (as control group) were
      examined by immunohistochemistry using anti-NF-kappaB p65, anti-Ki-67 and anti
      MMP-9 antibodies and by in situ hybridization(ISH)using anti-MMP-9 mRNA probes.
      Immunohistochemical reactivity for NF-kappaB was mainly detected in the cytoplasm
      of tumor cells, and nuclear reactivity was only seen in few tumor cells in COC
      and classic ameloblastomas. Rate of nuclear staining was less than 1%. The
      expression of Ki-67 in GCOC was significantly higher than those in CCOT
      (p<0.001), DGCT and ameloblastoma (p<0.005). In COCs and ameloblastomas,
      expression of MMP-9 mRNA and protein was detected in tumor cells as well as in
      stromal cells. The positive staining for MMP-9 protein was detected in stromal
      cells of all GCOC cases and was significantly stronger than those in CCOT and
      DGCT groups (p<0.05). NF-kappaB may minimally affect the progression and local
      invasiveness of CCOT, DGCT and GCOC. GCOC show significantly higher proliferative
      activity than CCOT and DGCT. MMP-9 in stroma is associated with invasive ability
      of the CCOT, DGCT and GCOC.

PMID- 18723388
TI  - Growth of ninhydrin single crystal and its characterization.
AB  - A novel organic nonlinear optical crystal ninhydrin having good optical quality
      was grown by solution technique using aqua solution. The quality of the crystal
      was also examined by high-resolution X-ray diffraction study. Solubility studies
      were made at different temperatures. Functional groups present in the grown
      material were identified from the vibrational frequencies of recorded FTIR
      spectrum. Transmittance of the crystal was recorded using the UV-vis-NIR
      spectrophotometer. From the thermal analysis it was observed that the material
      exhibits single sharp melting point. The fluorescence spectrum of ninhydrin was
      recorded. The Vicker's microhardness values were measured for the grown crystal.
      Second harmonic generation conversion efficiency estimated using Kurtz and Perry
      method is about five times that of KDP.

PMID- 18723389
TI  - Organizational factors affecting successful adoption of innovative eHealth
      services: a case study employing the FITT framework.
AB  - OBJECTIVE: The paper presents an application of the "Fit between Individuals,
      Task and Technology" (FITT) framework to analyze the socio-organizational
      technical factors that influence IT adoption in the healthcare domain. METHOD:
      The FITT framework was employed as the theoretical instrument for a retrospective
      analysis of a 15-year effort in implementing IT systems and eHealth services in
      the context of a Regional Health Information Network in Crete. Quantitative and
      qualitative research methods, interviews and participant observations were
      employed to gather data from a case study that involved the entire region of
      Crete. RESULTS: The detailed analysis of the case study based on the FITT
      framework, showed common features, but also differences of IT adoption within the
      various health organizations. The emerging picture is a complex nexus of factors
      contributing to IT adoption, and multi-level interventional strategies to promote
      IT use. CONCLUSION: The work presented in this paper shows the applicability of
      the FITT framework in explaining the complexity of aspects observed in the
      implementation of healthcare information systems. The reported experiences reveal
      that fit management can be viewed as a system with a feedback loop that is never
      really stable, but ever changing based on external factors or deliberate
      interventions. Management of fit, therefore, becomes a constant and complex task
      for the whole life cycle of IT systems.

PMID- 18723390
TI  - Human herpesvirus 8 DNA quantification in matched plasma and PBMCs samples of
      patients with HHV8-related lymphoproliferative diseases.
AB  - BACKGROUND: The quantitative evaluation of human herpesvirus 8 (HHV8) DNA is not
      well described in the clinical management of HHV8-related lymphoproliferative
      diseases. OBJECTIVES: To evaluate and to compare HHV8 viral load in different
      blood compartments from patients with multicentric Castleman's disease (MCD),
      primary effusion lymphoma (PEL) and HHV8-associated solid lymphoma (SLY) and to
      establish which clinical sample would be preferable for HHV8 DNA testing. STUDY
      DESIGN: We assessed HHV8 DNA in plasma and peripheral blood mononuclear cells
      (PBMCs) paired samples from 7 PEL, 8 MCD, 2 SLY HIV+ patients at the diagnosis
      and during the course of the illness by using a real time PCR assay. RESULTS:
      HHV8 viremia was always detectable at diagnosis. HHV8 DNA levels were correlated
      in matched pairs of samples at diagnosis and during follow-up (Spearman
      correlation coefficient: r=0.83, p<0.001 and r=0.73, p<0.001, respectively). The
      performance characteristics of the PCR assay with both materials did not show
      disparity by the analysis of the receiver operating characteristic (ROC) curve
      (X(1)(2)=0.50; p=0.48). CONCLUSIONS: Plasma or PBMCs are both adequate samples
      for HHV8 DNA quantification and Real time PCR provides a reliable method to
      estimate viral replication in patients with HHV8-related lymphoproliferations,
      where HHV8 viral load is a consistent feature.

PMID- 18723391
TI  - Reliability of transcranial magnetic stimulation for mapping swallowing
      musculature in the human motor cortex.
AB  - OBJECTIVE: Although transcranial magnetic stimulation (TMS) has been widely used
      to study motor cortex organization and excitability, the reliability of this
      technique has not been thoroughly investigated. Furthermore, previous reports of
      TMS reliability have been restricted to upper limb musculature. We sought to
      determine the test-retest reliability for TMS mapping of motor representations
      for swallowing musculature. METHODS: Twenty healthy volunteers were tested twice
      over two weeks using TMS to determine motor threshold, map area, map volume,
      maximal MEP site location and maximal MEP site size for the suprahyoid complex
      and pharyngeal musculature. RESULTS: Good test-retest reliability was found in
      both swallowing muscle sites for the following test parameters: motor map area,
      maximal MEP site location: lateral coordinate, maximal MEP site size and motor
      threshold (ICC=0.76-0.98). Moderate reliability was observed for motor map volume
      and maximal MEP site location: anterior-posterior coordinate (ICC=0.68-0.74).
      CONCLUSIONS: TMS assessments of motor representation size, location and
      excitability appear to be highly reproducible, although the reliability of these
      measures may vary according to the specific muscle under investigation.
      SIGNIFICANCE: These works provide much needed psychometric data to validate the
      use of TMS to assess the cortical representation of swallowing musculature.

PMID- 18723392
TI  - Sternomastoid evoked potentials in response to skull taps reveal two aspects of
      vestibular function.

PMID- 18723393
TI  - Central processing of tactile and nociceptive stimuli in complex regional pain
      syndrome.
AB  - OBJECTIVE: Patients with complex regional pain syndrome (CRPS) suffer from
      continuous regional limb pain and from hyperesthesia to touch and pain. To better
      understand the pathophysiological mechanisms underlying the hyperesthesia of CRPS
      patients, we investigated their cortical processing of touch and acute pain.
      METHODS: Cortical responses to tactile stimuli applied to the thumbs, index and
      little fingers (D1, D2, and D5) and nociceptive stimuli delivered to dorsa of the
      hands were recorded with a whole-scalp neuromagnetometer from eight chronic CRPS
      patients and from nine healthy control subjects. RESULTS: In the patients,
      primary somatosensory (SI) cortex activation to tactile stimulation of D2 was
      significantly stronger, and the D1-D5 distance in SI was significantly smaller
      for the painful hand compared to the healthy hand. The PPC activation to tactile
      stimulation was significantly weaker in the patients than in the control
      subjects. To nociceptive stimulation with equal laser energy, the secondary
      somatosensory (SII) cortices and posterior parietal cortex (PPC) were similarly
      activated in both groups. The PPC source strength correlated with the pain rating
      in the control subjects, but not in the patients. CONCLUSIONS: The enhanced SI
      activation in hyperesthetic CRPS patients may reflect central sensitization to
      touch. The decreased D1-D5 distance implies permanent changes in SI hand
      representations in chronic CRPS. The defective PPC activation could be associated
      with the neglect-like symptoms of the patients. As the SII and PPC responses were
      not enhanced in the CRPS patients, other brain areas are likely to contribute to
      the observed hyperesthesia to pain. SIGNIFICANCE: Our results indicate changes of
      somatosensory processing at cortical level in CRPS.

PMID- 18723394
TI  - Interference of short-interval intracortical inhibition (SICI) and short-interval
      intracortical facilitation (SICF).
AB  - OBJECTIVE: Short-interval intracortical inhibition (SICI) is a widely used paired
      pulse transcranial magnetic stimulation (TMS) measure to assess inhibition in
      human motor cortex. However, facilitatory processes may contaminate SICI under
      certain conditions. Here, we specifically address the contribution of short
      interval intracortical facilitation (SICF). METHODS: A SICF interstimulus
      interval (ISI) curve was obtained in nine healthy subjects according to an
      established paired-pulse TMS protocol [Ziemann U, Tergau F, Wassermann EM,
      Wischer S, Hildebrandt J, Paulus W. Demonstration of facilitatory I-wave
      interaction in the human motor cortex by paired transcranial magnetic
      stimulation. J Physiol (Lond) 1998a;511:181-190]. The individual ISI leading to
      SICF peak1, trough1, peak2, trough2 and peak3 was selected for the subsequent
      measurement of SICI intensity curves (SICI(peak1), SICI(trough1), SICI(peak2),
      SICI(trough2), SICI(peak3)) using intensity variation of the first stimulus (S1)
      from 50% to 120% of active motor threshold (AMT) in the first dorsal interosseous
      muscle. RESULTS: SICI(peak1) (mean ISI, 1.54ms) and SICI(trough1) (mean ISI,
      1.97ms) showed a sigmoid SICI increase with S1 intensity. SICI(trough1) reached
      the strongest SICI and was therefore chosen for comparison with the other SICI
      curves. SICI(peak2) (mean ISI, 2.61ms) was U-shaped with a similar increase at
      low S1 intensities, but a decrease when S1 intensity exceeded 90% AMT.
      Correlation analyses suggested that this decrease was caused by SICF.
      SICI(trough2) (mean ISI, 3.50ms) and SICI(peak3) (mean ISI, 4.26ms) showed
      considerably less inhibition than SICI(trough1) over the whole range of S1
      intensities. CONCLUSIONS: Findings show that commonly accepted protocols of
      testing SICI (ISI of 2-3ms, S1 intensity approximately 95% AMT) bear the risk of
      measuring net inhibition contaminated by SICF. SIGNIFICANCE: SICF may contribute
      to apparently reduced SICI in patients with neurological or psychiatric
      disorders.

PMID- 18723396
TI  - Cuban parasitology in review: a revolutionary triumph.
AB  - Although the population of Hispaniola, Cuba's most similar neighbour in the
      Caribbean, continues to be threatened by parasitic diseases (including malaria),
      many tropical parasitic infections in Cuba have been eliminated or controlled.
      However, some parasitic infections remain important in the Cuban population, and
      the occurrence of vectors and the high possibility of introduction of parasites
      mean that Cuban diagnosticians must remain alert. Some key aspects of human
      parasitology in Cuba are reviewed here, including historical information,
      comparative data from Hispaniola and Jamaica, and how Cuba strives to maintain
      and improve its control against parasitic infections. Data from recent key novel
      parasitology research conducted in Cuba are also described.

PMID- 18723395
TI  - Planomonadida ord. nov. (Apusozoa): ultrastructural affinity with Micronuclearia
      podoventralis and deep divergences within Planomonas gen. nov.
AB  - Gliding zooflagellates previously misidentified as Ancyromonas sigmoides,
      Metopion or Heteromita constitute a new genus Planomonas. Three new Planomonas
      species (marine P. micra and P. mylnikovi: freshwater P. limna) have extremely
      divergent 18S rRNA and subtly but consistently different light microscopic
      morphology, distinguishable from P. (=Ancyromonas) melba comb. nov. and P.
      (=Bodo) cephalopora comb. nov. Ultrastructurally, P. micra and P. mylnikovi have
      a sub-plasma membrane dense pellicular layer (except in the ventral feeding
      pocket whose rim is supported by microtubules), kinetocysts, and flat
      mitochondrial cristae. Centrioles, connected at approximately 80 degrees by short
      fibres, have a dense amorphous distal plate below a double axosome and four
      microtubular roots. Microbody, mitochondrion, and dictyosomes associate with the
      nucleus. Longitudinal cytokinesis is slow and peculiar; ciliary transformation is
      from anterior to posterior as in other bikonts. Planomonads, like the non
      flagellate Micronuclearia (here grouped with planomonads as Hilomonadea cl.
      nov.), have an indistinguishable single dense pellicular layer, not a double
      layer like apusomonads (comprising emended class Thecomonadea, phylum Apusozoa).
      We also sequenced 18S rDNA for Planomonas howeae sp. nov. and Micronuclearia
      podoventralis, plus actin genes of P. micra, Micronuclearia, Amastigmonas marina.
      All were analysed phylogenetically; the Planomonas clade is ancient, diverse and
      robust: it sometimes groups weakly as sister to Micronuclearia.

PMID- 18723397
TI  - Control of blood utilization.
AB  - Blood utilization may be viewed as the response to any one of three questions.
      How much blood is transfused? Who are recipients? Why did the physician prescribe
      the blood products? Considerable data exists to answer the first question, and
      some data exists regarding the second. However, answering the third question is
      the real key to the control of blood utilization.

PMID- 18723398
TI  - Computational identification of 48 potato microRNAs and their targets.
AB  - MicroRNAs (miRNAs) are a new family of small RNA molecules known in animals and
      plants, whose conservation among species suggests that they bear conserved
      biological functions. So far, little is known about miRNA in Solanum tuberosum
      species. Using previously known miRNAs from Arabidopsis, rice and other plant
      species against expressed sequence tags (ESTs), genomic survey sequence (GSS) and
      nucleotide databases, we identified 48 potential miRNAs in S. tuberosum. These
      potato miRNAs may regulate 186 potential targets, which are involved in floral,
      leaf, root, and stem development, signal transduction, metabolism pathways, and
      stress responses. To validate the prediction of miRNAs in potato, we performed a
      RT-PCR analysis and found that potato miRNAs have diverse expression patterns
      during development.

PMID- 18723399
TI  - Identifying the target mRNAs of microRNAs in colorectal cancer.
AB  - MicroRNAs (miRNAs) play an important role in gene regulatory networks by
      inhibiting the expression of target mRNAs. There is a growing interest in
      identifying the relationship between miRNAs and their target mRNAs. Various
      experimental studies have been carried out to discover miRNAs involved in cancer
      and to identify their target genes. At the same time, a large volume of miRNA and
      mRNA expression profiles have become available owing to the development of high
      throughput measurement technologies. So, there is now a pressing need to develop
      a computational method by which we can identify the target mRNAs of given miRNAs
      from such massive expression data sets. In this respect, we propose an effective
      linear model based identification method to unravel the relationship between
      miRNAs and their target mRNAs in colorectal cancer by using microarray expression
      profiles and sequence data.

PMID- 18723400
TI  - Protein subcellular location prediction using optimally weighted fuzzy k-NN
      algorithm.
AB  - Optimally weighted fuzzy k-nearest neighbors (OWFKNN) algorithm has been used to
      predict proteins' subcellular locations based on their amino acid composition, in
      this paper. The datasets used consists of two species which are 997 prokaryotic
      and 2427 eukaryotic protein sequences. The overall prediction accuracy achieved
      is about 88.5% for prokaryotic sequences and 86.2% for eukaryotic sequences in a
      jackknife test. Compared to other algorithms developed for the prediction of
      protein subcellular location, OWFKNN gives very satisfying results. Therefore,
      OWFKNN can be used as an alternative method to predict protein localization.

PMID- 18723402
TI  - Role of the anaesthetist in obstetric critical care.
AB  - The anaesthetist plays a key role in the management of high-risk pregnancies, and
      must be a member of the multidisciplinary team that is required to care for the
      critically ill obstetric patient. Anaesthetists are trained in advanced life
      support and resuscitation. They are experienced in the management of the
      critically ill, and provide anaesthesia, sedation and pain management. The
      obstetric anaesthetist should undertake education of medical and midwifery staff
      in the early recognition, monitoring and treatment of the sick mother,
      resuscitation training, running 'skills drills' for emergency simulations, risk
      management and audit of maternal morbidity on the labour ward. To date, there is
      little evidence to inform the anaesthetic management of the critically ill
      obstetric patient; most recommendations and guidelines are based on the
      management of non-obstetric, critically ill patients. Management must be adapted
      to encompass the physiological changes of pregnancy. Evidence-based guidelines on
      management of the critically ill woman with specific obstetric conditions are
      also lacking.

PMID- 18723403
TI  - Sympathetic activity at rest and motor brain areas: FDG-PET study.
AB  - Although recent studies identified brain areas which are involved in short term
      activation of the sympathetic nervous system, little is known about brain
      mechanisms which generate the individual variability of basal autonomic activity.
      In this fluorodeoxyglucose positron emission tomography study (FDG-PET), we aimed
      to identify brain regions, which covary with function parameters of the autonomic
      nervous system at rest. Therefore, FDG-PET (Siemens, Germany) was performed twice
      in 14 healthy resting subjects (7 m, 7 f; mean age 29.5 years) while different
      parameters of autonomic function were assessed simultaneously: Blood pressure,
      heart rate, power spectra of heart rate variability (HF/LF ratio) and plasma
      catecholamines. In order to control for attention, subjects had to focus visual
      affective neutral presentations during the experiment. Correlation analysis was
      performed as a region of interest analysis using SPM2 software (p<0.001
      uncorrected). Sympathetic activity at rest varied substantially between subjects.
      There were significant positive correlations between increase of regional
      cerebral glucose metabolism (rCGM) of the heads of caudate nuclei on both sides
      and the HF/LF ratio of heart rate variability. Furthermore, significant negative
      correlations between both heart rate and plasma catecholamines and rCGM decreases
      of caudate nuclei heads were found. In addition, there was a positive correlation
      between plasma catecholamines and primary motor cortex activation. Autonomic
      nervous system at rest seems to be partially interlocked with activity of motor
      brain regions - the caudate nuclei and the motor cortex. This might have clinical
      implications for the understanding of stress-related disorders, which are
      frequently accompanied by increased sympathetic activity as well as muscle tone.

PMID- 18723405
TI  - Capillary electrophoresis method optimized with a factorial design for the
      determination of glutathione and amino acid status using human capillary blood.
AB  - Plasma aromatic and sulfur containing amino acids are good indicators of protein
      anabolism/catabolism, while blood reduced and oxidized glutathione reflect
      oxidative status in an organism. Using a full factorial design for screening
      important variables (pH, concentration, temperature) we developed a capillary
      zone electrophoresis method permitting their measurements in the single run,
      without any derivatization procedures. The best separations were obtained within
      less than 30 min employing a 10 mmol/l phosphate buffer, pH 2.8, 18 degrees C, 15
      kV voltage. Fairly good precision with a linear relationship between peak area
      and concentrations (r=0.995-0.999) were obtained. The method was used to analyze
      human capillary blood.

PMID- 18723404
TI  - Development of selective media for the isolation of yeasts and filamentous fungi
      from the sputum of adult patients with cystic fibrosis (CF).
AB  - Yeasts and filamentous fungi are beginning to emerge as significant microbial
      pathogens in patients with cystic fibrosis (CF), particularly in relation to
      allergic-type responses, as seen in patients with allergic bronchopulmonary
      aspergillosis (ABPA), Aspergillus bronchitis and in invasive fungal disease in
      lung transplant patients. Four fungal media were compared in this study,
      including Sabouraud Dextrose Agar (SDA) and Medium B, with and without the
      addition of selective antibiotics, where antibiotic-supplemented media were
      designated with (+). These media were compared for their ability to suppress
      contaminating, mainly Gram-ve pathogens, in CF sputa (Pseudomonas aeruginosa,
      Burkholderia cepacia complex [BCC] organisms) and to enhance the growth of fungi
      present in CF sputum. Medium B consisted of glucose (16.7 g/l), agar (20 g/l),
      yeast extract (30 g/l) and peptone (6.8 g/l) at pH 6.3 and both SDA(+) and Medium
      B(+) were supplemented with cotrimethoxazole, 128 mg/l; chloramphenicol, 50 mg/l;
      ceftazidime, 32 mg/l; colistin, 24 mg/l). Employment of SDA(+) or Medium B(+)
      allowed an increase in specificity in the detection of yeasts and moulds, by
      42.8% and 39.3%, respectively, over SDA when used solely. SDA(+) had a greater
      ability than Medium B(+) to suppress bacterial growth from predominantly Gram-ve
      co-colonisers. This is a significant benefit when attempting to detect and
      isolate fungi from the sputum of CF patients, as it largely suppressed any
      bacterial growth, with the exception of the BCC organisms, thus allowing for an
      increased opportunity to detect target fungal organisms in sputum and represented
      a significant improvement over the commercial medium (SDA), which is currently
      used. Overall, both novel selective media were superior in their ability to
      suppress bacteria in comparison with the commercially available SDA medium, which
      is routinely employed in most clinical microbiology diagnostic laboratories
      presently. Alternatively, Medium B(+) had a great ability to grow fungi than
      SDA(+) and when employed together, the specificity of combined use was 82%, with
      a sensitivity for yeasts, filamentous fungi, and combined overall fungi of 96.0%,
      92.3% and 96.0%, respectively. Overall, when employing one fungal selective
      medium for the routine detection of yeasts and filamentous fungi in the sputum of
      CF patients, we would recommend employment of Medium B(+). However, we would
      recommend the combined employment of SDA(+) and Medium B(+), in order to
      synergistically isolate and detect the greatest number of fungi present in CF
      sputa.

PMID- 18723406
TI  - Comparative study of coated and immobilized polysaccharide-based chiral
      stationary phases and their applicability in the resolution of enantiomers.
AB  - The enantioselective and chromatographic properties of Chiralpak AD and Chiralpak
      IA as well as those of Chiralcel OD and Chiralpak IB have been evaluated using a
      set of 48 compounds that differ in their physical and chemical properties. The
      impact of the different immobilisation methodologies of the chiral
      polysaccharide, i.e., coated or immobilized on retention and enantioselectivity
      was studied. The study on immobilized chiral stationary phases (CSPs) was
      expanded to also include mobile phases containing mixtures of alkanes and more
      non-conventional solvents such as ethyl acetate, ethers, acetone and
      dichloromethane. In this paper we report some of the general trends observed for
      the 48 racemic compounds with respect to retention, alpha and Rs. Further, the
      impact of the immobilisation methodology and the choice of the mobile phase on
      the elution order of the enantiomers is also discussed.

PMID- 18723407
TI  - Simultaneous determination of hydrochlorothiazide, quinapril and quinaprilat in
      human plasma by liquid chromatography-tandem mass spectrometry.
AB  - A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method has been developed and validated for the simultaneous estimation of
      hydrochlorothiazide, quinapril and its metabolite quinaprilat in human plasma.
      After solid phase extraction (SPE), the analytes and IS were chromatographed on a
      hypurity C8 (100 mm x 2.1 mm i.d., 5 microm particle size) column using 2 microL
      injection volume with a run time of 2.8 min. An isocratic mobile phase consisting
      of 0.5% (v/v) formic acid:acetonitrile (25:75, v/v) was used to separate all
      these drugs. The precursor and product ions of these drugs were monitored on a
      triple quadrupole mass spectrometer, operating in the multiple reaction
      monitoring mode (MRM) without polarity switch. The proposed method was validated
      over the range of 5-500 ng/mL for hydrochlorothiazide method and 5-1500 ng/mL for
      quinapril and quinaprilat. Inter-batch and intra-batch precision (coefficient of
      variation - % CV) across five validation runs lower limit of quantitation (LLOQ),
      lower quality control (LQC), middle quality control (MQC), higher quality control
      (HQC) and upper limit of quantitation (ULOQ) was less than 15. The accuracy
      determined at these levels was within +/-13% in terms of relative percentage
      error.

PMID- 18723408
TI  - LC-ESI-MS determination and pharmacokinetics of adrafinil in rats.
AB  - A highly sensitive and specific liquid chromatography/tandem mass spectrometric
      (LC-MS/MS) method for investigating the pharmacokinetics of adrafinil in rats was
      developed. Rat serum pretreated by solid-phase extraction (SPE) was analyzed by
      LC-MS/MS with an electrospray ionization (ESI) interface. The mobile phase
      consisted of acetonitrile:water:acetic acid (35:65:0.1, v/v/v) in an isocratic
      elution mode pumped at 1.0 ml/min. The analytical column (250 mm x 4.6 mm i.d.)
      was packed with Kromasil C(18) material (5.0 microm). The standard curve was
      linear from 16.5 to 5000 ng/ml. The assay was specific, accurate (R.S.D.<2.6%),
      precise and reproducible (within- and between-day precisions R.S.D. <7.0% and
      <9.0%, respectively). Adrafinil in rat serum was stable over three freeze-thaw
      cycles at ambient temperature for 6 h. The method had a lower limit of
      quantitation of 16.5 ng/ml, which offered high sensitivity for the determination
      of adrafinil in serum. The method was successfully applied to pharmacokinetic
      studies of adrafinil after an oral administration to rats.

PMID- 18723409
TI  - Biochromatographic framework for analyzing magnesium chloride salt dependence on
      nor-NOHA binding to arginase enzyme.
AB  - Our group demonstrated recently that arginase I inhibition reduces endothelial
      dysfunction and blood pressure rising in spontaneously hypertensive rats [C.
      Demougeot, A. Prigent-Tessier, C. Marie, A. Berthelot, J. Hypertens. 23 (2005)
      971; C. Demougeot, A. Prigent-Tessier, T. Bagnost, C. Andre, Y. Guillaume, M.
      Bouhaddi, C. Marie, A. Berthelot, Life Sci. 80 (2007) 1128]. This discovery opens
      interesting perspectives in the development of new drugs against hypertension. As
      well, in a previous paper [T. Bagnost, Y.C. Guillaume, M. Thomassin, J.F. Robert,
      A. Berthelot, A. Xicluna, C. Andre, J. Chromatogr. B: Analyt. Technol. Biomed.
      Life Sci. 856 (2007) 113], a novel biochromatographic column was developed in our
      laboratory for studying the binding of N(omega)-hydroxy-nor-l-arginine (nor
      NOHA), an arginase inhibitor, with this enzyme. In this manuscript, using this
      novel biochromatographic concept, the effect of magnesium chloride on the nor
      NOHA/arginase binding was analyzed for the first time. This study demonstrated
      that the salt ions interacted with arginase and played a great role in the nor
      NOHA/arginase association. For a salt concentration (x) in the medium less than
      3mM, the nor-NOHA/arginase binding decreased with x due to a decrease of the
      charge-charge interactions between nor-NOHA and its arginase binding site. Above
      3mM of salt in the medium, the affinity of nor-NOHA to arginase increased
      slightly with x because the net number of ions (n) (Mg(2+) or Cl(-)) released or
      bound upon complex formation is low. As well, it was clearly demonstrated, that
      above 3 mM the n value depend on the salt concentration in the bulk solvent and
      was approximately nil for x=12 mM. This dependence was due to a gradual and
      conformational change of the arginase enzyme which around 12 mM adopted a less
      flexible structure; its binding site was thus less accessible to nor-NOHA and nor
      NOHA-arginase association decreased slightly.

PMID- 18723410
TI  - An HPLC-ultraviolet detection method for the determination of Z24 in mouse whole
      blood and its application to pharmacokinetic studies.
AB  - A sensitive and reproducible high-performance liquid chromatography (HPLC)-UV
      method for the determination of Z24, a tumorigenesis and angiogenesis inhibitor,
      has been developed and validated in mouse whole blood. Blood samples were
      extracted with ether, evaporated, and the residue was reconstituted in mobile
      phase. An aliquot was separated by isocratic reversed-phase HPLC on a Hypersil
      ODS-2 column and quantified using UV detection at 390 nm. The mobile phase was
      50% (v/v) acetonitrile/water with a flow rate of 0.8 ml/min. A linear curve over
      the concentration range of 0.05-6 microg/ml (r(2)=0.9976) was obtained. The
      coefficient of the variation for the intra- and inter-day precision ranged from
      3.0 to 10.9% and 5.7 to 10.3%, respectively. The absolute recovery of Z24 was
      89.2-108.5%. The method is simple, economical and sufficient for in vivo
      pharmacokinetic studies on Z24. Nonlinear pharmacokinetics was found in mice at
      doses from 20 to 80 mg/kg.

PMID- 18723411
TI  - Exploring enantiospecific ligand-protein interactions using cellular membrane
      affinity chromatography: chiral recognition as a dynamic process.
AB  - The chiral recognition mechanisms responsible for the enantioselective binding on
      the alpha3beta4 nicotinic acetylcholine receptor (alpha3 beta4 nAChR) and human
      organic cation transporter 1 (hOCT1) have been reviewed. The results indicate
      that chiral recognition on the alpha3beta4 nAChR is a process involving initial
      tethering of dextromethorphan and levomethorphan at hydrophobic pockets within
      the central lumen followed by hydrogen bonding interactions favoring
      dextromethorphan. The second step is the defining enantioselective step. Studies
      with the hOCT1 indentified four binding sites within the transporter that
      participated in chiral recognition. Each of the enantiomers of the compounds used
      in the study interacted with three of these sites, while (R)-verapamil interacted
      with all four. Chiral recognition arose from the conformational adjustments
      required to produce optimum interactions. With respect to the prevailing
      interaction-based models, the data suggest that chiral recognition is a dynamic
      process and that the static point-based models should be amended to reflect this.

PMID- 18723412
TI  - Using graphical chain models to analyze differences in structural correlates of
      undernutrition in Benin and Bangladesh.
AB  - Undernutrition among children is one of the most important health problems in
      developing countries. In order to understand the complex pathways affecting
      undernutrition which is crucial for policy interventions, one needs to explicitly
      model the dependence chain of immediate, intermediate, and underlying factors
      affecting undernutrition. Graphical chain models are used here to investigate the
      determinants of undernutrition in Benin and Bangladesh. While the dependence
      chain affecting undernutrition contains many common elements, the influence of
      demographic, cultural, and socioeconomic factors seems to have stronger direct
      and indirect influences in Benin than in Bangladesh, where many socioeconomic and
      gender related factors have a more direct influence on undernutrition.

PMID- 18723413
TI  - Randomised controlled trial of paediatric magnetic positioning device assisted
      colonoscopy: a pilot and feasibility study.
AB  - BACKGROUND AND AIMS: Complete colonoscopy is critical for the evaluation of many
      paediatric gastrointestinal diseases. The aim of the study was to investigate the
      feasibility of magnetic positioning device for paediatric colonoscopy and to
      compare completion rate and procedure time with and without the device. METHODS:
      Prospective randomised controlled trial of standard colonoscopy compared to
      magnetic positioning device assisted colonoscopy in children and adolescents ages
      7-20 years was performed. RESULTS: Analysis showed that the proportion of
      successfully completed colonoscopies were 19/20 (95%) in the MP arm versus 17/18
      (94.4%) in the SC arm, p=NS. The median time to complete colonoscopy to the cecum
      was 16.5 min (range 6-52 min) in the MP arm and 12 min (range 6-33 min) in the SC
      arm, p=NS. CONCLUSIONS: Our preliminary data suggest that the use of magnetic
      positioning device for colonoscopy is feasible in paediatric patients. These data
      suggest that the use of magnetic positioning device may not be of benefit for
      experienced endoscopists who achieved very high colonoscopy completion rates
      without the MP device. Further studies are needed to determine its role in
      paediatric colonoscopy since this device may be of more benefit for physicians in
      training.

PMID- 18723414
TI  - Appearance-based comments, body dissatisfaction and drive for muscularity in
      males.
AB  - This study examined the role of positive and negative appearance-based comments
      on body dissatisfaction and drive for muscularity among young adult males. The
      direct and moderating effect of self-esteem were also investigated; and BMI, age,
      and social desirability were included as covariates. The participants were 214
      males aged between 18 and 30 years. More frequent negative comments were
      associated with higher body dissatisfaction whilst more frequent positive
      comments were associated with lower body dissatisfaction. However, both frequent
      negative and positive commentary were associated with higher drive for
      muscularity. Self-esteem was also associated with both body dissatisfaction and
      the drive for muscularity, but it did not moderate that influence of either
      positive or negative messages. Longitudinal research is now needed to determine
      the directionality of these relationships. Further research is required to
      establish the contexts in which positive and negative messages are associated
      with body dissatisfaction and the drive for muscularity.

PMID- 18723415
TI  - Poly(MAA-co-AN) hydrogels with improved mechanical properties for theophylline
      controlled delivery.
AB  - A hydrophobically improved copolymer hydrogel was constructed and developed based
      on methacrylic acid (MAA) and acrylonitrile (AN) monomers. The swelling
      investigations indicated that the hydrogels were highly sensitive to the pH and
      ionic strength of the surrounding environment. The swelling ratios of the gels in
      stimulated intestinal fluids (SIF, pH 7.4) were higher than those in stimulated
      gastric fluids (SGF, pH 1.4), and followed a non-Fickian and a Fickian diffusion
      mechanism, respectively. The results match well with scanning electron microscopy
      observations showing that mesh sizes in hydrogels in SGF are larger and more
      patulous than in SIF. It is believed that the phenomena are concerned with the
      electrostatic repulsion originating from the formation and dissociation of
      carboxyl groups, as well as a charge screening effect of the cations leading to
      the reduction of osmotic pressure. A dynamic mechanical analyzer revealed that
      the addition of hydrophobic AN units notably improved the compression mechanical
      properties of the control sample. With an increase in AN concentrations, the
      ability for the copolymers to resist compression deformation enhanced in
      distilled water and the compression strains have almost the same values in SIF
      environments. Differential scanning calorimetry was used to analyze the state of
      water and to determine the amounts of freezing and non-freezing water. The
      controlled release examination based on the theophylline model drug showed that
      the release rate in distilled water was faster than that in SIF or SGF. The
      introduction of the hydrophobic AN decreased the theophylline release rates in
      both SIF and SGF, and the release rate variation in SIF was notably larger than
      that in SGF. The drug release behavior of the AN-modified P(MAA-co-AN) copolymer
      hydrogel deviates from the Fickian diffusion control mechanism. This hydrogel is
      expected to be used as an excellent material in oral drug controlled release.

PMID- 18723416
TI  - Poly(N-isopropylacrylamide-co-acrylamide) cross-linked thermoresponsive
      microspheres obtained from preformed polymers: Influence of the physico-chemical
      characteristics of drugs on their release profiles.
AB  - Poly(N-isopropylacrylamide-co-acrylamide) copolymer was synthesized as an
      interesting thermoresponsive material possessing a phase transition temperature
      of around 36 degrees C in phosphate buffer, pH 7.4 (PB); the concentration was
      10%, w/v. The copolymer maintains a sharp phase transition at a relatively high
      percentage of acrylamide. The lower critical solution temperature (LCST) of the
      copolymer is influenced by the concentration of copolymer solution in PB. The
      copolymer was transformed in thermoresponsive microspheres by chemical cross
      linking of amide groups with glutaraldehyde. The key factors for the successful
      preparation of microspheres are the use of a concentrated polymer solution, a
      temperature (38 degrees C) that is high enough but lower than LCST, and a long
      reaction time (48h). The microspheres were characterized by optical and scanning
      electron microscopy, swelling/deswelling kinetics, swelling degree, and PB
      retention at different temperatures. Finally, the influence of
      hydrophilicity/hydrophobicity and the molecular weight of the drugs (propranolol,
      lidocaine, vitamin B(12)) on their release profile from thermoresponsive
      microspheres were examined. Above LCST the hydrogel matrix is in the dehydrated
      state and hydrophobic interactions between the hydrophobic drugs and the polymer
      occur, modulating the release rate of the drugs. For hydrophilic drugs, the
      release rate is modulated mainly by the steric interaction between the drug
      molecule and the matrix.

PMID- 18723417
TI  - Gelatin/chitosan/hyaluronan scaffold integrated with PLGA microspheres for
      cartilage tissue engineering.
AB  - Poly(lactide-co-glycotide) (PLGA) microspheres integrated into
      gelatin/chitosan/hyaluronan scaffolds were fabricated by freeze-drying and
      crosslinking with 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide. The effects of
      the microspheres on porosity, density, compressive modulus, phosphate-buffered
      saline uptake ratio and weight loss of the scaffolds were evaluated. Generally, a
      scaffold with a higher PLGA content had a lower porosity and weight loss, and a
      medium uptake ratio, but a larger apparent density and compressive modulus. When
      the PLGA content was lower than 50%, the PLGA-integrated scaffolds had a similar
      pore size (approximately 200microm) as that of the control, and as much as 90% of
      their porosity could be preserved. In vitro chondrocyte culture in the 50% PLGA
      integrated scaffold demonstrated that the cells could proliferate and secrete
      extracellular matrix at the same level as in the control
      gelatin/chitosan/hyaluronan scaffold.

PMID- 18723418
TI  - American Association of Clinical Endocrinologists, The Obesity Society, and
      American Society for Metabolic & Bariatric Surgery Medical guidelines for
      clinical practice for the perioperative nutritional, metabolic, and nonsurgical
      support of the bariatric surgery patient.

PMID- 18723419
TI  - World Stroke Day 2008: "little strokes, big trouble".

PMID- 18723420
TI  - Impact of fever on outcome in patients with stroke and neurologic injury: a
      comprehensive meta-analysis.
AB  - BACKGROUND AND PURPOSE: Many studies associate fever with poor outcome in
      patients with neurological injury, but this relationship is blurred by divergence
      in populations and outcome measures. We sought to incorporate all recent
      scholarship addressing fever in brain-injured patients into a comprehensive meta
      analysis to evaluate disparate clinical findings. METHODS: We conducted a Medline
      search for articles since January 1, 1995 (in English with abstracts, in humans)
      and hand searches of references in bibliographies and review articles. Search
      terms covered stroke, neurological injury, thermoregulation, fever, and cooling.
      A total of 1139 citations were identified; we retained 39 studies with 67 tested
      hypotheses contrasting outcomes of fever/higher body temperature and
      normothermia/lower body temperature in patients with neurological injury covering
      14431 subjects. A separate meta-analysis was performed for each of 7 outcome
      measures. Significance was evaluated with Zc developed from probability values or
      t values. Correlational effect size, r (es), was calculated for each study and
      used to derive Cohen's d unbiased combined effect size and relative risk.
      RESULTS: Fever or higher body temperature was significantly associated with worse
      outcome in every measure studied. Relative risk of worse outcome with fever was:
      mortality, 1.5; Glasgow Outcome Scale, 1.3; Barthel Index, 1.9; modified Rankin
      Scale, 2.2; Canadian Stroke Scale, 1.4; intensive care length of stay, 2.8; and
      hospital length of stay, 3.2. CONCLUSIONS: In the pooled analyses covering 14431
      patients with stroke and other brain injuries, fever is consistently associated
      with worse outcomes across multiple outcome measures.

PMID- 18723421
TI  - Rapidly increased neuronal mitochondrial biogenesis after hypoxic-ischemic brain
      injury.
AB  - BACKGROUND AND PURPOSE: Mitochondrial biogenesis is regulated through the
      coordinated actions of both nuclear and mitochondrial genomes to ensure that the
      organelles are replenished on a regular basis. This highly regulated process has
      been well defined in skeletal and heart muscle, but its role in neuronal cells,
      particularly when under stress or injury, is not well understood. In this study,
      we report for the first time rapidly increased mitochondrial biogenesis in a rat
      model of neonatal hypoxic/ischemic brain injury (H-I). METHODS: Postnatal day 7
      rats were subjected to H-I induced by unilateral carotid artery ligation followed
      by 2.5 hours of hypoxia. The relative amount of brain mitochondrial DNA (mtDNA)
      was measured semiquantitatively using long fragment PCR at various time points
      after H-I. HSP60 and COXIV proteins were detected by Western blot. Expression of
      three genes critical for the transcriptional regulation of mitochondrial
      biogenesis, peroxisome proliferator-activated receptor coactivator-1 (PGC-1),
      nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A
      (TFAM), were examined by Western blot and RT-PCR. RESULTS: Brain mtDNA content
      was markedly increased 6 hours after H-I, and continued to increase up to 24
      hours after H-I. Paralleling the temporal change in mtDNA content, mitochondrial
      number and proteins HSP60 and COXIV, and citrate synthase activity were increased
      in neurons in the cortical infarct border zone after H-I. Moreover, cortical
      expression of NRF-1 and TFAM were increased 6 to 24 hours after H-I, whereas PGC
      1 was not changed. CONCLUSIONS: Neonatal H-I brain injury rapidly induces
      mitochondrial biogenesis, which may constitute a novel component of the
      endogenous repair mechanisms of the brain.

PMID- 18723422
TI  - Use of carotid intima-media thickness to identify patients with ischemic stroke
      and transient ischemic attack with low yield of cardiovascular sources of embolus
      on transesophageal echocardiography.
AB  - BACKGROUND AND PURPOSE: Carotid intima-media thickness (CIMT) is associated with
      systemic atherosclerosis and cardioembolic conditions and predicts the risk of
      recurrent strokes. We sought to establish the relationship between CIMT and
      cardiovascular sources of embolus (CSE) on transesophageal echocardiography (TEE)
      and hypothesized that a noninvasive strategy of CIMT assessment and transthoracic
      echocardiography bubble study would identify patients with ischemic stroke or
      transient ischemic attack in whom TEE would provide little incremental diagnostic
      yield. METHODS: In 180 patients with ischemic stroke or transient ischemic attack
      of undetermined origin referred for TEE, we prospectively performed CIMT
      measurement/plaque screen (Phase 1, n=96) or CIMT measurement/plaque screen and
      transthoracic echocardiography bubble study (Phase 2, n=84) before TEE. Phase 1
      results were used to construct receiver operating characteristic curves to
      demonstrate the ability of CIMT to detect CSE on TEE and to identify the optimal
      CIMT cutoff value for prospective strategy testing (Phase 2). RESULTS: In Phase
      1, CIMT was found to correlate with TEE markers of aortic atherosclerosis,
      including complex aortic plaques, and combined CSE. The optimal CIMT cutoff for
      detection of CSE on TEE was 0.78 mm. In Phase 2, a positive noninvasive strategy
      test (CIMT >or=0.78 mm, +carotid plaque, and/or a positive transthoracic
      echocardiography bubble study) was present in 61%. The prevalence of CSE on TEE
      was significantly higher among those with a positive compared with a negative
      noninvasive strategy test (65% versus 9%, P<0.001), and this strategy had a
      sensitivity of 92% and a negative predictive value of 91% for the detection of
      any CSE on TEE. CONCLUSIONS: In patients with stroke or transient ischemic attack
      of undetermined origin, a noninvasive strategy of CIMT assessment/plaque screen
      and transthoracic echocardiography bubble study can identify patients in whom
      further invasive evaluation with TEE will be of low diagnostic yield.

PMID- 18723423
TI  - The role of carotid artery stenting and carotid endarterectomy in cognitive
      performance: a systematic review.
AB  - BACKGROUND AND PURPOSE: Change in cognition is being increasingly recognized as
      an important outcome measure; however, the role of carotid revascularization on
      this issue remains to be determined. It is still under debate whether carotid
      artery stenting and carotid endarterectomy have the same influence on
      neuropsychological functions. SUMMARY OF REVIEW: This article systematically
      reviews recent literature in an attempt to clarify this issue. A total of 32
      papers reporting on neurocognition after carotid endarterectomy (n=25), carotid
      artery stenting (n=4), or carotid artery stenting versus carotid endarterectomy
      (n=3) were identified. The studies were different for many methodological
      factors, eg, sample size, type of patients and control group, statistical
      measure, type of test, timing of assessment, and so on. There was a lack of
      consensus in defining the improvement or impairment after either carotid artery
      stenting or carotid endarterectomy. Furthermore, there were nonuneqivocal results
      regarding the same domain of assessment (memory, visuomotor, attention). Based on
      available evidence, it is probable that carotid endarterectomy as well as carotid
      artery stenting do not change neuropsychological function "per se." CONCLUSIONS:
      Assessment of cognition after carotid revascularization is probably influenced by
      many confounding factors such as learning effect, type of test, type of patients,
      and control group, which are often minimized in their importance. The role of
      carotid revascularization is to prevent stroke in patients with severe carotid
      stenosis as highlighted by previous large randomized trials. Although an effect
      of carotid revascularization on cognition could be missed as a consequence of
      underpowered studies included in this review, at this time, no prediction can be
      done regarding its repercussions on higher intellectual functions. Larger studies
      appropriately designed and powered to assess cognition after carotid
      revascularization might change this view.

PMID- 18723424
TI  - Soluble CD36 in plasma is increased in patients with symptomatic atherosclerotic
      carotid plaques and is related to plaque instability.
AB  - BACKGROUND AND PURPOSE: The risk for cardiovascular events is related to the
      composition and stability of an atherosclerotic plaque driven by inflammation and
      deposition of lipids. Scavenger receptors are a family of cell surface receptors
      involved in lipid uptake and inflammation. Recently, we found that soluble CD36
      is increased in plasma from patients with diabetes strongly correlated with
      insulin resistance. METHODS: We tested whether soluble CD36 is a marker of plaque
      stability in patients with high-grade internal carotid stenoses (n=62). The
      patients were classified according to plaque symptomatology and plaque
      echogenicity on ultrasound examination. RESULTS: When patients were divided into
      3 groups according to the latest clinical symptoms from plaques (ie, symptoms
      within the last 2 months [n=16], symptoms within the last 2 to 6 months [n=15],
      or asymptomatic [n=31]), the former group had significantly raised plasma levels
      of soluble CD36 as compared with the other 2 groups. In contrast, we found no
      differences in plasma levels of C-reactive protein, beta-thromboglobulin, lipid
      parameters, or HbA1C between these groups. The patients with echolucent carotid
      plaques (n=20) tended to have higher soluble CD36 levels in plasma compared with
      those with echogenic/heterogenic plaque (n=39; P=0.087). By immunohistochemistry,
      CD36 was localized to macrophages-rich area of intima within the atherosclerotic
      lesion. CONCLUSIONS: We propose that sCD36 may be a marker of plaque instability
      and symptomatic carotid atherosclerosis, possibly at least partly as a result of
      CD36 release to the circulation from the foam cells within the atherosclerotic
      lesion.

PMID- 18723425
TI  - Quantitative assessment of core/penumbra mismatch in acute stroke: CT and MR
      perfusion imaging are strongly correlated when sufficient brain volume is imaged.
AB  - BACKGROUND AND PURPOSE: Our purpose was to determine (1) the correlation between
      quantitative CT and MR measurements of infarct core, penumbra, and mismatch; and
      (2) whether the difference between these measurements would alter patient
      selection for stroke clinical trials. METHODS: We studied 45 patients with acute
      middle cerebral artery stroke imaged a mean of 3.8 hours after onset (range, 0.48
      to 8.35 hours) who underwent CT perfusion and MR diffusion (DWI)/perfusion
      imaging within 3 hours of each other. The DWI and MR-mean transit time (MTT)
      abnormalities were visually segmented using a semiautomated commercial analysis
      program. The CT-cerebral blood volume) and CT-MTT lesions were automatically
      segmented using a relative cerebral blood volume threshold of 0.56 and a relative
      MTT threshold of 1.50 on commercially available software. Percent mismatch was
      defined as [(MTT-DWI)/DWI volume]x100. Pearson correlation coefficients were
      calculated. RESULTS: There were significant correlations for DWI versus CT
      cerebral blood volume lesion volumes (r2=0.88, P<0.001), for MR-MTT versus CT-MTT
      lesion volumes(r2=0.86, P<0.001), and for MR-MTT/DWI versus CT-MTT/CT-cerebral
      blood volume mismatch lesion volumes(r2=0.81, P<0.001). MR perfusion and CT
      perfusion agreed for determining: (1) infarct core < versus >or=100 mL in 41 of
      45 (91.1%); (2) MTT lesion size < versus >2 cm diameter in 42 of 45 (93.3%); (3)
      mismatch < versus >20% in 41 of 45 (91.1%); and (4) inclusion versus exclusion
      from trial enrollment in 38 of 45 (84.4%) patients. Six of 7 disagreements were
      due to inadequate CT coverage. CONCLUSIONS: Advanced MR and CT perfusion imaging
      measurements of core/penumbra mismatch for patient selection in stroke trials are
      highly correlated when CT perfusion coverage is sufficient to include most of the
      ischemic region. Although MR is currently the preferred imaging method for
      determining core and penumbra, CT perfusion is comparable and potentially more
      available.

PMID- 18723426
TI  - Favorable trends in the incidence and outcome in stroke in nondiabetic and
      diabetic subjects: findings from the Northern Sweden MONICA Stroke Registry in
      1985 to 2003.
AB  - BACKGROUND AND PURPOSE: Several studies indicate a declining case-fatality and
      mortality in stroke. Little is known about time trends in stroke for subjects
      with diabetes. The purpose of this study was to compare time trends in incidence,
      case-fatality and mortality for stroke patients with or without diabetes.
      METHODS: This study was based on the Northern Sweden MONICA Project Stroke
      registry during 1985 to 2003. 15 382 patients, aged 35 to 74 years, were included
      in the study. 11 605 had a first-ever stroke and 3777 had a recurrent stroke. In
      both men and women previously diagnosed diabetes was found in 22.8%. RESULTS: The
      incidence of stroke was 5 and 8 times higher in diabetic subjects than in
      nondiabetics, in men and women, respectively. Incidence of first-ever stroke
      decreased for nondiabetic men, probability value <0.001, and for diabetic women,
      probability value=0.012. Recurrent stroke incidence declined highly significant,
      probability value <0.001, in all but diabetic men. For diabetic women, the
      decrease in incidence in first and recurrent stroke was significantly greater
      than in nondiabetic women. Case-fatality and mortality in stroke declined for all
      groups except diabetic women with first-ever stroke. The time trends in case
      fatality and mortality did not differ significantly between nondiabetic and
      diabetic patients. CONCLUSIONS: The incidence of stroke declined in both
      nondiabetic and diabetic subjects except for diabetic men and for nondiabetic
      women with first-ever stroke. Case-fatality in first-ever stroke declined for all
      but diabetic women. This led to a decreased mortality over the 19-year period for
      both groups. This is the first time that the decline in stroke incidence is
      reported in this MONICA population.

PMID- 18723428
TI  - Five new pedigrees with inherited RUNX1 mutations causing familial platelet
      disorder with propensity to myeloid malignancy.
AB  - Familial platelet disorder with propensity to myeloid malignancy (FPD/AML) is an
      autosomal dominant syndrome characterized by platelet abnormalities and a
      predisposition to myelodysplasia (MDS) and/or acute myeloid leukemia (AML). The
      disorder, caused by inherited mutations in RUNX1, is uncommon with only 14
      pedigrees reported. We screened 10 families with a history of more than one first
      degree relative with MDS/AML for inherited mutations in RUNX1. Germ- line RUNX1
      mutations were identified in 5 pedigrees with a 3:2 predominance of N-terminal
      mutations. Several affected members had normal platelet counts or platelet
      function, features not previously reported in FPD/AML. The median incidence of
      MDS/AML among carriers of RUNX1 mutation was 35%. Individual treatments varied
      but included hematopoietic stem cell transplantation from siblings before
      recognition of the inherited leukemogenic mutation. Transplantation was
      associated with a high incidence of complications including early relapse,
      failure of engraftment, and posttransplantation lymphoproliferative disorder.
      Given the small size of modern families and the clinical heterogeneity of this
      syndrome, the diagnosis of FPD/AML could be easily overlooked and may be more
      prevalent than previously recognized. Therefore, it would appear prudent to
      screen young patients with MDS/AML for RUNX1 mutation, before consideration of
      sibling hematopoietic stem cell transplantation.

PMID- 18723430
TI  - Contributions of the medial temporal lobe to declarative memory retrieval:
      manipulating the amount of contextual retrieval.
AB  - We investigated how the hippocampus and its adjacent mediotemporal structures
      contribute to contextual and noncontextual declarative memory retrieval by
      manipulating the amount of contextual information across two levels of the same
      contextual dimension in a source memory task. A first analysis identified medial
      temporal lobe (MTL) substructures mediating either contextual or noncontextual
      retrieval. A linearly weighted analysis elucidated which MTL substructures show a
      gradually increasing neural activity, depending on the amount of contextual
      information retrieved. A hippocampal engagement was found during both levels of
      source memory but not during item memory retrieval. The anterior MTL including
      the perirhinal cortex was only engaged during item memory retrieval by an
      activity decrease. Only the posterior parahippocampal cortex showed an activation
      increasing with the amount of contextual information retrieved. If one assumes a
      roughly linear relationship between the blood-oxygenation level-dependent (BOLD)
      signal and the associated cognitive process, our results suggest that the
      posterior parahippocampal cortex is involved in contextual retrieval on the basis
      of memory strength while the hippocampus processes representations of item
      context binding. The anterior MTL including perirhinal cortex seems to be
      particularly engaged in familiarity-based item recognition. If one assumes
      departure from linearity, however, our results can also be explained by one
      dimensional modulation of memory strength.

PMID- 18723429
TI  - Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of
      unrelated donor umbilical cord blood transplantation in pediatric patients with
      hematologic malignancies.
AB  - Outcomes of unrelated donor cord blood transplantation in 191 hematologic
      malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled
      between 1999 and 2003 were studied (median follow-up, 27.4 months) in a
      prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching at
      enrollment was 6/6 (n = 17), 5/6 (n = 58), 4/6 (n = 111), or 3/6 (n = 5) by low
      resolution HLA-A, -B, and high-resolution (HR) DRB1. Retrospectively, 179 pairs
      were HLA typed by HR. The median precryopreservation total nucleated cell (TNC)
      dose was 5.1 x 10(7) TNC/kg (range, 1.5-23.7) with 3.9 x 10(7) TNC/kg (range, 0.8
      22.8) infused. The median time to engraftment (absolute neutrophil count >
      500/mm(3) and platelets 50 000/muL) was 27 and 174 days. The cumulative incidence
      of neutrophil engraftment by day 42 was 79.9% (95% confidence interval [CI],
      75.1%-85.2%); acute grades III/IV GVHD by day 100 was 19.5% (95% CI, 13.9%
      25.5%); and chronic GVHD at 2 years was 20.8% (95% CI, 14.8%-27.7%). HR matching
      decreased the probability of severe acute GVHD. The cumulative incidence of
      relapse at 2 years was 19.9% (95% CI, 14.8%-25.7%). The probabilities of 6-month
      and 2-year survivals were 67.4% and 49.5%. Unrelated donor cord blood
      transplantation from partially HLA-mismatched units can cure many children with
      leukemias. The study was registered at www.clinicaltrials.gov as #NCT00000603.

PMID- 18723432
TI  - Isoniazid or moxifloxacin in rifapentine-based regimens for experimental
      tuberculosis?
AB  - RATIONALE: Recent studies have demonstrated that combined substitutions of
      rifapentine for rifampin and moxifloxacin for isoniazid in the standard, daily,
      short-course regimen of rifampin, isoniazid, and pyrazinamide produces stable
      cure in 12 weeks or less. This study was designed to more precisely evaluate the
      contribution of moxifloxacin and isoniazid to rifapentine-based regimens.
      OBJECTIVES: We compared bactericidal activity and treatment-shortening potential
      between regimens consisting of isoniazid or moxifloxacin plus rifapentine and
      pyrazinamide administered either thrice-weekly or daily. METHODS: Using a mouse
      model of tuberculosis, we assessed bactericidal activity by performing
      quantitative cultures of lung homogenates over the first 12 weeks of treatment.
      Relapse rates were assessed after completing 8, 10, and 12 weeks of treatment to
      determine the duration of treatment necessary for stable cure. MEASUREMENTS AND
      MAIN RESULTS: After 4 weeks of treatment, daily and thrice-weekly therapy with
      rifapentine, moxifloxacin, and pyrazinamide was significantly more active than
      treatment with rifapentine, isoniazid, and pyrazinamide. By 8 weeks of treatment,
      all mice receiving the moxifloxacin-containing regimens were lung culture
      negative, whereas those mice receiving the isoniazid-containing regimens
      continued to be lung culture positive. However, the duration of treatment
      necessary to achieve stable cure was 10 weeks for daily regimens and 12 weeks for
      thrice-weekly regimens, regardless of whether isoniazid or moxifloxacin was used.
      All mice receiving standard daily therapy with rifampin, isoniazid, and
      pyrazinamide relapsed after 12 weeks of treatment. CONCLUSIONS: These results
      suggest that regimens consisting of isoniazid or moxifloxacin plus rifapentine
      and pyrazinamide may dramatically shorten the duration of treatment needed to
      cure human tuberculosis.

PMID- 18723431
TI  - The consolidation of object and context recognition memory involve different
      regions of the temporal lobe.
AB  - These experiments investigated the involvement of several temporal lobe regions
      in consolidation of recognition memory. Anisomycin, a protein synthesis
      inhibitor, was infused into the hippocampus, perirhinal cortex, insular cortex,
      or basolateral amygdala of rats immediately after the sample phase of object or
      object-in-context recognition memory training. Anisomycin infused into perirhinal
      or insular cortices blocked long-term (24 h), but not short-term (90 min) object
      recognition memory. Infusions into the hippocampus or amygdala did not impair
      object recognition memory. Anisomycin infused into the hippocampus blocked long
      term, but not short-term object-in-context recognition memory, whereas infusions
      administered into the perirhinal cortex, insular cortex, or amygdala did not
      affect object-in-context recognition memory. These results clearly indicate that
      distinct regions of the temporal lobe are differentially involved in long-term
      object and object-in-context recognition memory. Whereas perirhinal and insular
      cortices are required for consolidation of familiar objects, the hippocampus is
      necessary for consolidation of contextual information of recognition memory.
      Altogether, these results suggest that temporal lobe structures are
      differentially involved in recognition memory consolidation.

PMID- 18723433
TI  - Circulating microparticles from patients with septic shock exert protective role
      in vascular function.
AB  - RATIONALE: Sepsis is an archetypal condition with molecular links between
      inflammation and coagulation. Both events can be orchestrated by the interaction
      between circulating and vascular cells that under activation release
      microparticles. OBJECTIVES: We characterized circulating microparticles from both
      nonseptic subjects and patients with septic shock and evaluated their
      contribution to vascular function. METHODS: Circulating microparticles and their
      cell origin were measured in blood from 36 patients with septic shock and 18
      nonseptic subjects by flow cytometry. Microparticles were then injected
      intravenously into mice and vascular reactivity was assessed in aorta. Expression
      and activity of enzymes involved in nitric oxide (NO) and cyclooxygenase
      metabolite production were analyzed. MEASUREMENTS AND MAIN RESULTS: Circulating
      levels of microparticles and platelet- and endothelial-derived microparticles
      were increased in septic patients. Surprisingly, septic microparticles enhanced
      the sensitivity of contraction of mouse aorta in response to serotonin.
      Interestingly, septic microparticles enhanced the contraction of aorta from
      lipopolysaccharide-treated mice. This effect was linked neither to increased
      calcium entry nor to Rho kinase inhibitor-sensitive mechanisms. In addition, the
      effect of septic microparticles was not modified either by NO-synthase or
      cyclooxygenase-2 inhibitors, and was not associated with NO or O2-
      overproduction. The nonselective cyclooxygenase-2 inhibitor indomethacin reduced,
      and the specific thromboxane A2 antagonist SQ-29548 abolished, aortic contraction
      in mice treated with nonseptic and septic microparticles. The effect of septic
      microparticles was associated with increased thromboxane A2 production, and was
      sensitive to a selective thromboxane A2 antagonist. CONCLUSIONS: We provide
      evidence that increased circulating microparticles are protective against
      vascular hyporeactivity accounting for hypotension in patients with septic shock.

PMID- 18723434
TI  - Biomarkers of airway acidity and oxidative stress in exhaled breath condensate
      from grain workers.
AB  - RATIONALE: Grain workers report adverse respiratory symptoms due to exposures to
      grain dust and endotoxin. Studies have shown that biomarkers in exhaled breath
      condensate (EBC) vary with the severity of airway inflammation. OBJECTIVES: The
      purpose of the study was to evaluate biomarkers of airway acidity (pH and
      ammonium [NH(4)(+)]) and oxidative stress (8-isoprostane) in the EBC of grain
      workers. METHODS: A total of 75 workers from 5 terminal elevators participated.
      In addition to EBC sampling, exposure monitoring for inhalable grain dust and
      endotoxin was performed; spirometry, allergy testing, and a respiratory
      questionnaire derived from that of the American Thoracic Society were
      administered. MEASUREMENTS AND MAIN RESULTS: Dust and endotoxin levels ranged
      from 0.010 to 13 mg/m(3) (median, 1.0) and 8.1 to 11,000 endotoxin units/m(3)
      (median, 610) respectively. EBC pH values varied from 4.3 to 8.2 (median, 7.9);
      NH(4)(+) values from 22 to 2,400 microM (median, 420); and 8-isoprostane values
      from 1.3 to 45 pg/ml (median, 11). Univariate and multivariable analyses revealed
      a consistent effect of cumulative smoking and obesity with decreased pH and
      NH(4)(+), and intensity of grain dust and endotoxin with increased 8-isoprostane.
      Duration of work on the test day was associated with decreased pH and NH(4)(+),
      whereas duration of employment in the industry was associated with decreased 8
      isoprostane. CONCLUSIONS: Chronic exposures are associated with airway acidity,
      whereas acute exposures are more closely associated with oxidative stress. These
      results suggest that the collection of EBC may contribute to predicting the
      pathological state of the airways of workers exposed to acute and chronic
      factors.

PMID- 18723435
TI  - Circulating RNA transcripts identify therapeutic response in cystic fibrosis lung
      disease.
AB  - RATIONALE: Circulating leukocyte RNA transcripts are systemic markers of
      inflammation, which have not been studied in cystic fibrosis (CF) lung disease.
      Although the standard assessment of pulmonary treatment response is FEV(1), a
      measure of airflow limitation, the lack of systemic markers to reflect changes in
      lung inflammation critically limits the testing of proposed therapeutics.
      OBJECTIVES: We sought to prospectively identify and validate peripheral blood
      leukocyte genes that could mark resolution of pulmonary infection and
      inflammation using a model by which RNA transcripts could increase the predictive
      value of spirometry. METHODS: Peripheral blood mononuclear cells were isolated
      from 10 patients with CF and acute pulmonary exacerbations before and after
      therapy. RNA expression profiling revealed that 10 genes significantly changed
      with treatment when compared with matched non-CF and control subjects with stable
      CF to establish baseline transcript abundance. Peripheral blood mononuclear cell
      RNA transcripts were prospectively validated, using real-time polymerase chain
      reaction amplification, in an independent cohort of acutely ill patients with CF
      (n = 14). Patients who responded to therapy were analyzed using general
      estimating equations and multiple logistic regression, such that changes in
      FEV(1)% predicted were regressed with transcript changes. MEASUREMENTS AND MAIN
      RESULTS: Three genes, CD64, ADAM9, and CD36, were significant and independent
      predictors of a therapeutic response beyond that of FEV(1) alone (P < 0.05). In
      both cohorts, receiver operating characteristic analysis revealed greater
      accuracy when genes were combined with FEV(1). CONCLUSIONS: Circulating
      mononuclear cell transcripts characterize a response to the treatment of
      pulmonary exacerbations. Even in small patient cohorts, changes in gene
      expression in conjunction with FEV(1) may enhance current outcomes measures for
      treatment response.

PMID- 18723436
TI  - Particulate matter in cigarette smoke alters iron homeostasis to produce a
      biological effect.
AB  - RATIONALE: Lung injury after cigarette smoking is related to particle retention.
      Iron accumulates with the deposition of these particles. OBJECTIVES: We tested
      the postulate that (1) injury after smoking correlates with exposure to the
      particulate fraction of cigarette smoke, (2) these particles alter iron
      homeostasis, triggering metal accumulation, and (3) this alteration in iron
      homeostasis affects oxidative stress and inflammation. METHODS: Rats and human
      respiratory epithelial cells were exposed to cigarette smoke, filtered cigarette
      smoke, and cigarette smoke condensate (the particulate fraction of smoke), and
      indices of iron homeostasis, oxidative stress, and inflammatory injury were
      determined. Comparable measures were also evaluated in nonsmokers and smokers.
      MEASUREMENTS AND MAIN RESULTS: After exposure of rats to cigarette smoke,
      increased lavage concentrations of iron and ferritin, serum ferritin levels, and
      nonheme iron concentrations in the lung and liver tissue all increased. Lavage
      ascorbate concentrations were decreased, supporting an oxidative stress. After
      filtering of the cigarette smoke to remove particles, most of these changes were
      reversed. Exposure of cultured respiratory epithelial cells to cigarette smoke
      condensate caused a similar accumulation of iron, metal-dependent oxidative
      stress, and increased IL-8 release. Lavage samples in healthy smokers and smoking
      patients with chronic obstructive pulmonary disease revealed elevated
      concentrations of both iron and ferritin relative to healthy nonsmokers. Lavage
      ascorbate decreased with cigarette smoking. Serum iron and ferritin levels among
      smokers were increased, supporting systemic accumulation of this metal after
      cigarette smoke exposure. CONCLUSIONS: We conclude that cigarette smoke particles
      alter iron homeostasis, both in the lung and systemically.

PMID- 18723437
TI  - Long-term erythromycin therapy is associated with decreased chronic obstructive
      pulmonary disease exacerbations.
AB  - RATIONALE: Frequent chronic obstructive pulmonary disease (COPD) exacerbations
      are a major cause of hospital admission and mortality and are associated with
      increased airway inflammation. Macrolides have airway antiinflammatory actions
      and may reduce the incidence of COPD exacerbations. OBJECTIVES: To determine
      whether regular therapy with macrolides reduces exacerbation frequency. METHODS:
      We performed a randomized, double-blind, placebo-controlled study of erythromycin
      administered at 250 mg twice daily to patients with COPD over 12 months, with
      primary outcome variable being the number of moderate and/or severe exacerbations
      (treated with systemic steroids, treated with antibiotics, or hospitalized).
      MEASUREMENTS AND MAIN RESULTS: We randomized 109 outpatients: 69 (63%) males, 52
      (48%) current smokers, mean (SD) age 67.2 (8.6) years, FEV1 1.32 (0.53) L, FEV1%
      predicted 50 (18)%. Thirty-eight (35%) of the patients had three or more
      exacerbations in the year before recruitment, with no differences between
      treatment groups. There were a total of 206 moderate to severe exacerbations: 125
      occurred in the placebo arm. Ten in the placebo group and nine in the macrolide
      group withdrew. Generalized linear modeling showed that the rate ratio for
      exacerbations for the macrolide-treated patients compared with placebo-treated
      patients was 0.648 (95% confidence interval: 0.489, 0.859; P = 0.003) and that
      these patients had shorter duration exacerbations compared with placebo. There
      were no differences between the macrolide and placebo arms in terms of stable
      FEV1, sputum IL-6, IL-8, myeloperoxidase, bacterial flora, serum C-reactive
      protein, or serum IL-6 or in changes in these parameters from baseline to first
      exacerbation over the 1-year study period. CONCLUSIONS: Macrolide therapy was
      associated with a significant reduction in exacerbations compared with placebo
      and may be useful in decreasing the excessive disease burden in this important
      patient population. Clinical trial registered with www.clinicaltrials.gov (NCT
      00147667).

PMID- 18723439
TI  - Alpha1-antitrypsin inhibits the activity of the matriptase catalytic domain in
      vitro.
AB  - Matriptase is a type II transmembrane protease that is characterized by an N
      terminal transmembrane and multiple extracellular domains, in addition to the
      conserved extracellular serine protease catalytic domain. The expression pattern
      of matriptase suggests that this protease may play broad roles in the biology of
      surface lining epithelial cells. In this study we report that alpha1-antitrypsin
      (AAT), an endogenous inhibitor of serine proteases, inhibits the catalytic domain
      of human recombinant matriptase in vitro. Co-incubation of AAT with matriptase
      (at a molar ratio 1:2) resulted in the formation of heat stable complexes,
      clearly seen in sodium dodecyl sulfate electrophoresis and Western blots. AAT was
      found to be a slow, tight-binding inhibitor of the catalytic domain of matriptase
      with a second order reaction rate constant of 0.31 x 10(3) M(-1)s(-1). Notably,
      the oxidized form of AAT, which lacks serine protease inhibitor activity, failed
      to generate matriptase complexes and to inhibit matriptase activity. Since
      matriptase is involved in a number of physiologic processes, including activation
      of epithelial sodium channels, our findings offer considerable new insights into
      new regulatory function of AAT in vivo.

PMID- 18723440
TI  - Epithelial sodium channel inhibition in primary human bronchial epithelia by
      transfected siRNA.
AB  - Na(+) absorption and Cl(-) secretion are in equilibrium to maintain an
      appropriate airway surface fluid volume and ensure appropriate mucociliary
      clearance. In cystic fibrosis, this equilibrium is disrupted by mutations in the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in the
      absence of functional CFTR protein, which in turn results in deficient cAMP
      dependent Cl(-) secretion and predominant Na(+) absorption. It has been suggested
      that down-regulation of the epithelial sodium channel, ENaC, might help to
      restore airway hydration and reverse the airway phenotype in patients with cystic
      fibrosis. We used an siRNA approach to analyze the possibility of down-regulating
      ENaC function in bronchial epithelia and examine the resulting effects on fluid
      transport. siRNA sequences complementary to each of the three ENaC subunits have
      been used to establish whether single subunit down-regulation is enough to reduce
      Na(+) absorption. Transfection was performed by exposure to siRNA for 24 hours at
      the time of cell seeding on permeable support. By using primary human bronchial
      epithelial cells we demonstrate that (1) siRNA sequences complementary to ENaC
      subunits are able to reduce ENaC transcripts and Na(+) channel activity by 50 to
      70%, (2) transepithelial fluid absorption decreases, and (3) these functional
      effects last at least 8 days. A decrease in ENaC mRNA results in a significant
      reduction of ENaC protein function and fluid absorption through the bronchial
      epithelium, indicating that an RNA interference approach may improve the airway
      hydration status in patients with cystic fibrosis.

PMID- 18723438
TI  - Amicus or adversary: platelets in lung biology, acute injury, and inflammation.
AB  - Platelets are the chief effector cells in hemostasis and have additional major
      functions in inflammation, vascular integrity, and tissue repair. Platelets and
      the lungs have interrelated activities. Previous studies provide evidence that
      platelets contribute to pulmonary vascular barrier function and are required for
      defense against pulmonary hemorrhage, and that the lungs can influence platelet
      number and distribution. There is also evidence that platelets contribute to
      pathologic syndromes of pulmonary inflammation and thrombosis. Thus, platelets
      have an "amicus or adversary" relationship with the lung. Recent observations and
      discoveries have established new paradigms relevant to influences of platelets on
      lung cell and molecular biology. These new findings are in a variety of areas
      including thrombopoieis, nontraditional activities of platelets, new synthetic
      capabilities and mechanisms of post-translational gene expression, interactions
      of platelets with endothelial cells and contributions to alveolar capillary
      barrier permeability, interactions of platelets with myeloid leukocytes, and
      platelet involvement in stem cell signaling and vascular repair. These issues are
      considered in a translational approach, with an emphasis on acute lung injury and
      the acute respiratory distress syndrome.

PMID- 18723441
TI  - Expression of profibrotic mediators in small airways versus parenchyma after
      cigarette smoke exposure.
AB  - Cigarette smoke-induced lung disease presents a morphologic contradiction in that
      the small airways become fibrotic but the parenchyma becomes emphysematous over
      time. To examine the mechanisms behind these phenomena, we exposed mice to
      cigarette smoke for up to 6 months and isolated small airways from histologic
      sections by laser capture microdissection. We then removed residual airway tissue
      and vessels, and collected the remaining parenchymal tissue. Gene expression of
      13 fibrogenic growth/signaling factors (particularly TGF-beta-related genes),
      matrix proteins, or enzymes involved in matrix production was examined by real
      time RT-PCR. Combining present and previously published data from our laboratory,
      in the airways over the long term there was a sustained and marked increase in
      expression of almost all of these genes. By contrast, in the parenchyma,
      expression of most genes was elevated at 2 and 24 hours after initial exposure,
      and all were elevated at 1 month; but by 6 months, when emphysema was present,
      most genes (9/13) were either at control values or down-regulated below control.
      At 3 months, several genes that were considerably elevated at 1 month were back
      to control levels, suggesting that loss of the parenchymal response precedes the
      development of emphysema. We conclude that with smoke exposure the airways
      demonstrate an ongoing profibrotic/proelastogenic response and the parenchyma a
      generally anti-fibrotic/anti-elastogenic response, but one that develops only
      with long-term exposure to smoke. These observations support the idea that the
      parenchyma largely fails to repair smoke-induced matrix damage, but this
      phenomenon is a relatively late event.

PMID- 18723442
TI  - Increased endothelial mitogen-activated protein kinase phosphatase-1 expression
      suppresses proinflammatory activation at sites that are resistant to
      atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease of arteries. It is triggered by
      proinflammatory mediators which induce adhesion molecules (eg, vascular cell
      adhesion molecule [VCAM]-1) in endothelial cells (ECs) by activating p38 and c
      Jun N-terminal kinase (JNK) mitogen-activated protein (MAP) kinases by
      phosphorylation. Blood flow influences atherosclerosis by exerting shear stress
      (mechanical drag) on the inner surface of arteries, a force that alters
      endothelial physiology. Regions of the arterial tree exposed to high shear are
      protected from endothelial activation, inflammation, and atherosclerosis, whereas
      regions exposed to low or oscillatory shear are susceptible. We examined whether
      MAP kinase phosphatase (MKP)-1, a negative regulator of p38 and JNK, mediates the
      antiinflammatory effects of shear stress. We observed that expression of MKP-1 in
      cultured ECs was elevated by shear stress, whereas the expression of VCAM-1 was
      reduced. MKP-1 induction was shown to be necessary for the antiinflammatory
      effects of shear stress because gene silencing of MKP-1 restored VCAM-1
      expression in sheared ECs. Immunostaining revealed that MKP-1 is preferentially
      expressed by ECs in a high-shear, protected region of the mouse aorta and is
      necessary for suppression of EC activation at this site, because p38 activation
      and VCAM-1 expression was enhanced by genetic deletion of MKP-1. We conclude that
      MKP-1 induction is required for the antiinflammatory effects of shear stress.
      Thus, our findings reveal a novel molecular mechanism contributing to the spatial
      distribution of vascular inflammation and atherosclerosis.

PMID- 18723443
TI  - Vascular endothelial growth factor and semaphorin induce neuropilin-1 endocytosis
      via separate pathways.
AB  - The neuropilin (Nrp)1 receptor is essential for both nervous and vascular system
      development. Nrp1 is unusually versatile, because it transmits both
      chemoattractive and repulsive signals in response to vascular endothelial growth
      factor (VEGF)-A and class 3 semaphorins, respectively. Both Nrp1 and VEGF
      receptor 2 undergo ligand-dependent endocytosis. We sought to establish the
      endocytic pathway of Nrp1 and to determine whether uptake is required for its
      signaling. Whereas Nrp1 underwent clathrin-dependent endocytosis in response to
      VEGFA(165) treatment, semaphorin 3C (sema3C) induced lipid raft-dependent
      endocytosis. The myosin VI PDZ (postsynaptic density 95, Disk large, Zona
      occludens-1) adaptor protein synectin was essential for Nrp1 trafficking. Sema3C
      failed to inhibit migration of synectin(-/-) endothelial cells, mirroring the
      lower migratory response of these cells to VEGFA(165). These results show that
      the endocytic pathway of Nrp1 is determined by its ligand and that the
      trafficking of Nrp1 is essential for its signaling.

PMID- 18723444
TI  - Statins use a novel Nijmegen breakage syndrome-1-dependent pathway to accelerate
      DNA repair in vascular smooth muscle cells.
AB  - Although the hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are
      widely used in atherosclerosis to reduce serum cholesterol, statins have multiple
      other effects, including direct effects on cells of the vessel wall. Recently,
      DNA damage, including telomere shortening, has been identified in vascular smooth
      muscle cells (VSMCs) in human atherosclerosis. Although statins reduce DNA damage
      in vitro, the mechanisms by which they might protect DNA integrity in VSMCs are
      unknown. We show that human atherosclerotic plaque VSMCs exhibit increased levels
      of double-stranded DNA breaks and basal activation of DNA repair pathways
      involving ataxia telangiectasia-mutated (ATM) and the histone H2AX in vivo and in
      vitro. Oxidant stress induced DNA damage and activated DNA repair pathways in
      VSMCs. Statin treatment did not reduce oxidant stress or DNA damage but markedly
      accelerated DNA repair. Accelerated DNA repair required both the Nijmegen
      breakage syndrome (NBS)-1 protein and the human double minute protein Hdm2,
      accompanied by phosphorylation of Hdm2, dissociation of NBS-1 and Hdm2,
      inhibition of NBS-1 degradation, and accelerated phosphorylation of ATM. Statin
      treatment reduced VSMC senescence and telomere attrition in culture, accelerated
      DNA repair and reduced apoptosis in vivo after irradiation, and reduced ATM/ATR
      (ATM and Rad3-related) activity in atherosclerosis. We conclude that statins
      activate a novel mechanism of accelerating DNA repair, dependent on NBS-1
      stabilization and Hdm2. Statin treatment may delay cell senescence and promote
      DNA repair in atherosclerosis.

PMID- 18723445
TI  - Pbx/Meis deficiencies demonstrate multigenetic origins of congenital heart
      disease.
AB  - Congenital heart diseases are traditionally considered to be multifactorial in
      pathogenesis resulting from environmental and genetic interactions that determine
      penetrance and expressivity within a genetically predisposed family. Recent
      evidence suggests that genetic contributions have been significantly
      underestimated. However, single gene defects occur only in a minority of cases,
      and multigenetic causes of congenital heart diseases have not been fully
      demonstrated. Here, we show that interactions between alleles of 3 Pbx genes,
      which encode homeodomain transcription factors, are sufficient to determine the
      phenotypic presentation of congenital heart diseases in mice. A major role is
      served by Pbx1, whose inactivation results in persistent truncus arteriosus.
      Reduction or absence of Pbx2 or Pbx3 leads to Pbx1 haploinsufficiency and
      specific malformations that resemble tetralogy of Fallot, overriding aorta with
      ventricular septal defect, and bicuspid aortic valves. Disruption of Meis1, which
      encodes a Pbx DNA-binding partner, results in cardiac anomalies that resemble
      those caused by Pbx mutations. Each of the observed cardiac defects represents
      developmental abnormalities affecting distinct stages of cardiac outflow tract
      development and corresponds to specific types of human congenital heart disease.
      Thus, varied deficiencies in the Pbx gene family produce a full spectrum of
      cardiac defects involving the outflow tract, providing a framework for
      determining multigenetic causes of congenital heart anomalies.

PMID- 18723446
TI  - Cellular signaling underlying atrial tachycardia remodeling of L-type calcium
      current.
AB  - Atrial tachycardia (AT) downregulates L-type Ca(2+) current (I(CaL)) and causes
      atrial fibrillation-promoting electric remodeling. This study assessed potential
      underlying signal transduction. Cultured adult canine atrial cardiomyocytes were
      paced at 0, 1, or 3 Hz (P0, P1, P3) for up to 24 hours. Cellular tachypacing (P3)
      mimicked effects of in vivo AT: decreased I(CaL) and transient outward current
      (I(to)), unchanged I(CaT), I(Kr), and I(Ks), and reduced action potential
      duration (APD). I(CaL) was unchanged in P3 at 2 and 8 hours but decreased by 55+/
      6% at 24 hours. Tachypacing caused Ca(2+)(i) accumulation in P3 cells at 2 to 8
      hours, but, by 24 hours, Ca(2+)i returned to baseline. Ca(v)1.2 mRNA expression
      was not altered at 2 hours but decreased significantly at 8 and 24 hours (32+/-4%
      and 48+/-4%, respectively) and protein expression was decreased (47+/-8%) at 24
      hours only. Suppressing Ca(2+)(i) increases during tachypacing with the I(CaL)
      blocker nimodipine or the Ca(2+) chelator BAPTA-AM prevented I(CaL)
      downregulation. Calcineurin activity increased in P3 at 2 and 8 hours,
      respectively, returning to baseline at 24 hours. Nuclear factor of activated T
      cells (NFAT) nuclear translocation was enhanced in P3 cells. Ca(2+)-dependent
      signaling was probed with inhibitors of Ca(2+)/calmodulin (W-7), calcineurin (FK
      506), and NFAT (INCA6): each prevented I(CaL) downregulation. Significant APD
      reductions ( approximately 30%) at 24 hours in P3 cells were prevented by
      nimodipine, BAPTA-AM, W-7, or FK-506. Thus, rapid atrial cardiomyocyte activation
      causes Ca(2+) loading, which activates the Ca(2+)-dependent calmodulin
      calcineurin-NFAT system to cause transcriptional downregulation of I(CaL),
      restoring Ca(2+)i to normal at the cost of APD reduction. These studies elucidate
      for the first time the molecular feedback mechanisms underlying arrhythmogenic AT
      remodeling.

PMID- 18723447
TI  - Coadministration of endothelial and smooth muscle progenitor cells enhances the
      efficiency of proangiogenic cell-based therapy.
AB  - Cell-based therapy is a promising approach designed to enhance neovascularization
      and function of ischemic tissues. Interaction between endothelial and smooth
      muscle cells regulates vessels development and remodeling and is required for the
      formation of a mature and functional vascular network. Therefore, we assessed
      whether coadministration of endothelial progenitor cells (EPCs) and smooth muscle
      progenitor cells (SMPCs) can increase the efficiency of cell therapy. Unilateral
      hindlimb ischemia was surgically induced in athymic nude mice treated with or
      without intravenous injection of EPCs (0.5 x 10(6)), SMPCs (0.5 x 10(6)) and
      EPCs+SMPCs (0.25 x 10(6)+0.25 x 10(6)). Vessel density and foot perfusion were
      increased in mice treated with EPCs+SMPCs compared to animals receiving EPCs
      alone or SMPCs alone (P<0.001). In addition, capillary and arteriolar densities
      were enhanced in EPC+SMPC-treated mice compared to SMPC and EPC groups (P<0.01).
      We next examined the role of Ang-1/Tie2 signaling in the beneficial effect of EPC
      and SMPC coadministration. Small interfering RNA directed against Ang-1-producing
      SMPCs or Tie2-expressing EPCs blocked vascular network formation in Matrigel
      coculture assays, reduced the rate of incorporated EPCs within vascular
      structure, and abrogated the efficiency of cell therapy. Production of Ang-1 by
      SMPCs activates Tie2-expressing EPCs, resulting in increase of EPC survival and
      formation of a stable vascular network. Subsequently, the efficiency of EPC- and
      SMPC-based cotherapy is markedly increased. Therefore, coadministration of
      different types of vascular progenitor cells may constitute a novel therapeutic
      strategy for improving the treatment of ischemic diseases.

PMID- 18723448
TI  - Tbx3 is required for outflow tract development.
AB  - Conotruncal and ventricular septal congenital heart anomalies result from defects
      in formation and division of the embryonic outflow tract. Cardiac remodeling
      during outflow tract and ventricular septation converts the tubular embryonic
      heart into a parallel circulatory system with an independent left ventricular
      outlet and right ventricular inlet. Tbx3 encodes a T-box-containing transcription
      factor expressed in the developing conduction system of the heart. Mutations in
      TBX3 cause ulnar-mammary syndrome. Here we show that mice lacking Tbx3 develop
      severe outflow tract defects, including connection of both the aorta and
      pulmonary trunk with the right ventricle, in addition to aortic arch artery
      anomalies and abnormal communication between the right atrium and left ventricle.
      Alignment defects are preceded by a delay in caudal displacement of the arterial
      pole of the heart during aortic arch artery formation. Embryonic anterior
      posterior patterning and cardiac chamber development are unaffected in Tbx3
      mutant embryos. However, the contribution of second heart field derived
      progenitor cells to the arterial pole of the heart is impaired. Tbx3 is expressed
      in pharyngeal epithelia and neural crest cells in the pharyngeal region,
      suggesting an indirect role in second heart field deployment. Loss of Tbx3
      affects multiple signaling pathways regulating second heart field proliferation
      and outflow tract morphogenesis, including fibroblast growth factor signaling,
      leading to a failure of normal heart tube extension and consequent
      atrioventricular and ventriculoarterial alignment defects.

PMID- 18723449
TI  - Mechanisms underlying rate-dependent remodeling of transient outward potassium
      current in canine ventricular myocytes.
AB  - Transient outward K+ current (I to) downregulation following sustained
      tachycardia in vivo is usually attributed to tachycardiomyopathy. This study
      assessed potential direct rate regulation of cardiac I(to) and underlying
      mechanisms. Cultured adult canine left ventricular cardiomyocytes (37 degrees C)
      were paced continuously at 1 or 3 Hz for 24 hours. I to was recorded with whole
      cell patch clamp. The 3-Hz pacing reduced I to by 44% (P<0.01). Kv4.3 mRNA and
      protein expression were significantly reduced (by approximately 30% and
      approximately 40%, respectively) in 3-Hz paced cells relative to 1-Hz cells, but
      KChIP2 expression was unchanged. Prevention of Ca2+ loading with nimodipine or
      calmodulin inhibition with W-7, A-7, or W-13 eliminated 3-Hz pacing-induced I to
      downregulation, whereas downregulation was preserved in the presence of
      valsartan. Inhibition of Ca2+/calmodulin-dependent protein kinase (CaMK)II with
      KN93, or calcineurin with cyclosporin A, also prevented I to downregulation.
      CaMKII-mediated phospholamban phosphorylation at threonine 17 was increased in 3
      Hz paced cells, compatible with enhanced CaMKII activity, with functional
      significance suggested by acceleration of the Ca2+i transient decay time constant
      (Indo 1-acetoxymethyl ester microfluorescence). Total phospholamban expression
      was unchanged, as was expression of Na+/Ca2+ exchange and sarcoplasmic reticulum
      Ca2+-ATPase proteins. Nuclear localization of the calcineurin-regulated nuclear
      factor of activated T cells (NFAT)c3 was increased in 3-Hz paced cells compared
      to 1-Hz (immunohistochemistry, immunoblot). INCA-6 inhibition of NFAT prevented I
      to reduction in 3-Hz paced cells. Calcineurin activity increased after 6 hours of
      3-Hz pacing. CaMKII inhibition prevented calcineurin activation and NFATc3
      nuclear translocation with 3-Hz pacing. We conclude that tachycardia
      downregulates I to expression, with the Ca2+/calmodulin-dependent CaMKII and
      calcineurin/NFAT systems playing key Ca2+-sensing and signal-transducing roles in
      rate-dependent I to control.

PMID- 18723450
TI  - Understanding patient satisfaction, trust, and loyalty to primary care
      physicians.
AB  - The authors developed and empirically tested a model reflecting a system of
      interrelations among patient loyalty, trust, and satisfaction as they are related
      to patients' intentions to stay with a primary care physician (PCP) and recommend
      the doctor to other people. They used a structural equation modeling approach.
      The fit statistics indicate a well-fitting model: root mean square error of
      approximation = .022, goodness-of-fit index = .99, adjusted goodness-of-fit index
      = .96, and comparative fit index = 1.00. The authors found that patient trust and
      good interpersonal relationships with the PCP are major predictors of patient
      satisfaction and loyalty to the physician. Patients need to trust the PCP to be
      satisfied and loyal to the physician. The authors also found that patient trust,
      satisfaction, and loyalty are strong and significant predictors of patients'
      intentions to stay with the doctor and to recommend the PCP to others.

PMID- 18723451
TI  - Causes and metabolic consequences of Fatty liver.
AB  - Type 2 diabetes and cardiovascular disease represent a serious threat to the
      health of the population worldwide. Although overall adiposity and particularly
      visceral adiposity are established risk factors for these diseases, in the recent
      years fatty liver emerged as an additional and independent factor. However, the
      pathophysiology of fat accumulation in the liver and the cross-talk of fatty
      liver with other tissues involved in metabolism in humans are not fully
      understood. Here we discuss the mechanisms involved in the pathogenesis of
      hepatic fat accumulation, particularly the roles of body fat distribution,
      nutrition, exercise, genetics, and gene-environment interaction. Furthermore, the
      effects of fatty liver on glucose and lipid metabolism, specifically via
      induction of subclinical inflammation and secretion of humoral factors, are
      highlighted. Finally, new aspects regarding the dissociation of fatty liver and
      insulin resistance are addressed.

PMID- 18723452
TI  - Osteopathic approach to diastolic heart failure.

PMID- 18723453
TI  - Dangers of for-profit education: more than just words.

PMID- 18723454
TI  - Evidence-based publications: balancing research mission and our community's
      needs.

PMID- 18723455
TI  - Increased incidence and severity of somatic dysfunction in subjects with chronic
      low back pain.
AB  - CONTEXT: Patients with back pain make more than 14 million office visits per year
      to US physicians. Many of these patients have chronic low back pain (LBP) and are
      assumed to have more somatic dysfunction than those without chronic LBP.
      OBJECTIVE: To investigate incidence and severity of somatic dysfunction of four
      lumbar vertebral segments (L1-L4). METHODS: Sixteen subjects with chronic LBP and
      47 subjects without chronic LBP were each evaluated by two blinded examiners
      using reliable osteopathic palpatory tests. The incidence and severity of somatic
      dysfunction for each test were then analyzed within and between the study groups.
      RESULTS: Resistance to anterior springing (P<.001) and tenderness (P=.002) were
      found at significantly greater incidence in the chronic LBP group than in the non
      LBP group, but there were no significant differences between groups for incidence
      of tissue texture changes or static rotational asymmetry. Significantly greater
      severity of tissue texture changes (P=.006), static rotational asymmetry
      (P=.008), resistance to anterior springing (P<.001), and tenderness (P=.001) were
      observed in the chronic LBP group than in the non-LBP group. CONCLUSION: When
      compared with non-LBP subjects, chronic LBP subjects had overall greater severity
      for each of the four elements of somatic dysfunction evaluated, as well as
      greater incidence of resistance to anterior springing and tenderness. Somatic
      dysfunction is more severe in individuals with chronic LBP than in individuals
      without chronic LBP.

PMID- 18723456
TI  - Three-dimensional mathematical model for deformation of human fasciae in manual
      therapy.
AB  - CONTEXT: Although mathematical models have been developed for the bony movement
      occurring during chiropractic manipulation, such models are not available for
      soft tissue motion. OBJECTIVE: To develop a three-dimensional mathematical model
      for exploring the relationship between mechanical forces and deformation of human
      fasciae in manual therapy using a finite deformation theory. METHODS: The
      predicted stresses required to produce plastic deformation were evaluated for a
      volunteer subject's fascia lata, plantar fascia, and superficial nasal fascia.
      These stresses were then compared with previous experimental findings for plastic
      deformation in dense connective tissues. Using the three-dimensional mathematical
      model, the authors determined the changing amounts of compression and shear
      produced in fascial tissue during 20 seconds of manual therapy. RESULTS: The
      three-dimensional model's equations revealed that very large forces, outside the
      normal physiologic range, are required to produce even 1% compression and 1%
      shear in fascia lata and plantar fascia. Such large forces are not required to
      produce substantial compression and shear in superficial nasal fascia, however.
      CONCLUSION: The palpable sensations of tissue release that are often reported by
      osteopathic physicians and other manual therapists cannot be due to deformations
      produced in the firm tissues of plantar fascia and fascia lata. However, palpable
      tissue release could result from deformation in softer tissues, such as
      superficial nasal fascia.

PMID- 18723457
TI  - Emergency department tobacco cessation program: staff participation and
      intervention success among patients.
AB  - CONTEXT: The emergency department (ED) is often the primary source of healthcare
      for uninsured and underinsured patients. OBJECTIVES: To evaluate ED staff
      attitudes toward and participation in referring patients to a tobacco cessation
      program, and to assess the program's effectiveness. METHODS: A nonvalidated
      survey on smoking cessation and preventative services for ED patients was mailed
      to ED staff at a suburban hospital. After survey completion, ED staff was
      encouraged to refer smokers with diagnoses substantially worsened by tobacco use
      to a brief intervention delivered in the ED. An incentive was provided to staff
      beginning in the second month of the 3-month period. Referred patients were
      briefly counseled by a hospital social worker or an ED physician or nurse. Follow
      up telephone interviews with patients occurred 1 to 3 months postintervention.
      RESULTS: Of the 70 ED staff contacted, 63 (90%) responded to the survey. Most
      staff members (81%) agreed that they should facilitate clinical prevention. Fewer
      staff (60%) were comfortable advising patients to quit tobacco use (P<.03), and
      fewer still (51%) agreed that ED staff should assist patients in tobacco
      cessation (P<.001). Tobacco users were more likely to favor implementing patient
      education in the ED (P=.01) and were less comfortable advising patients to quit
      (P=.06). Staff referrals increased with program incentives (P=.008), with a total
      of 150 interventions occurring in the 3-month span. Of the 36 patients (24%)
      reached for follow-up, 13 (36%) attempted to quit and 6 (17%) succeeded. Overall,
      45% of the patients reached for follow-up either cut down or quit tobacco use.
      CONCLUSIONS: Staff members' attitudes toward tobacco cessation are not a firm
      barrier to the successful implementation of an ED tobacco cessation program. In
      addition, the ED provides an important opportunity to encourage patients to quit
      or cut down tobacco use.

PMID- 18723458
TI  - Osteopathic medicine and community health fairs: increasing public awareness
      while improving public health.
AB  - For members of the public, community health fairs are an opportunity to gather
      information and receive screening for a variety of common medical conditions. For
      the osteopathic medical community, they can be an opportunity to increase public
      awareness about osteopathic medicine. The authors conducted a survey at nine
      community-based health fairs in the Lansing, Mich, metropolitan area to determine
      public awareness of osteopathic medicine and to learn if event attendance later
      influenced attendees' decisions to seek medical care. Between November 2001 and
      February 2003, health fair attendees (N=202) completed questionnaires and had
      their blood pressure, glucose level, and cholesterol level measured and their
      body mass index calculated. Approximately half of study participants received
      telephone follow-up within 60 days. At that time, participants were asked the
      same survey questions as well as whether they had sought follow-up medical care
      in the past 30 days. Survey results suggest that higher levels of education
      (P<.001) and annual household income (P<.001) correlate with increased awareness
      of osteopathic physicians. Preference for osteopathic physicians over allopathic
      physicians correlates with lower age (P<.001) and higher levels of education
      (P=.004). One third of participants reported seeking medical care in the past 30
      days, but 79% of these individuals said their decisions were not influenced by
      health fair attendance. Health fairs are useful for increasing public knowledge
      about osteopathic medicine. The authors suggest that similar locally based
      promotion efforts target middle-aged individuals who do not have college degrees
      and belong to lower socioeconomic groups.

PMID- 18723459
TI  - Introducing osteopathic medical education in an allopathic residency.
AB  - BACKGROUND: Osteopathic medical school graduates, who are entering allopathic
      residencies in increasing numbers, want to maintain their osteopathic
      manipulative medicine (OMM) skills, but such residency programs do not include
      osteopathic curricula. OBJECTIVES: To describe the development and implementation
      of an osteopathic curriculum within an allopathic family medicine residency, and
      to evaluate the program's success. METHODS: Osteopathic residents, with the
      assistance of their allopathic faculty, generated the goals, objectives, and
      implementation strategies for an osteopathic curriculum that consisted of an
      osteopathic clinic and educational activities. The modified nominal group
      technique was used to determine the success of the clinic, highlighting its
      strengths and weaknesses. Success of the educational activities was measured by
      the American Osteopathic Association's approval of the residents' first year of
      postgraduate training. RESULTS: Osteopathic residents, who staffed the clinic,
      reported maintenance of their OMM skills to be the greatest strength of the
      clinic and lack of structured didactics to be its greatest weakness. Since the
      curriculum was introduced in 2004, 3 residents have applied for and received the
      American Osteopathic Association's approval for training. CONCLUSION: In the
      present study, an osteopathic curriculum was successfully implemented in an
      allopathic family medicine residency, enabling osteopathic residents to maintain
      their OMM skills. In addition to exploring the curriculum's impact on allopathic
      colleagues, further research should investigate whether osteopathic graduates who
      participate in such a curriculum are more likely to practice OMM after their
      residency ends.

PMID- 18723460
TI  - Pathological laughter in a patient with multiple sclerosis.
AB  - Pseudobulbar affect-such as pathological laughter or crying-is associated with
      several different neurologic diseases and is most frequently seen in patients
      with Alzheimer disease. However, many physicians do not recognize it as a symptom
      associated with multiple sclerosis. The present report describes a case of
      pathological laughter in a 56-year-old man who was diagnosed as having multiple
      sclerosis 20 years earlier.

PMID- 18723462
TI  - Election year's first shot over the bow: reforms needed.

PMID- 18723463
TI  - Keeping the flames of OMM burning.

PMID- 18723464
TI  - Increase efforts to promote primary care.

PMID- 18723465
TI  - Eliminating bad, bad medicine: problems with P4P initiatives.

PMID- 18723466
TI  - Spirituality is fundamental to osteopathic medicine.

PMID- 18723467
TI  - Rise and shine, rhinorrhea.

PMID- 18723468
TI  - ED physicians beware when using OMT for patients with motor vehicle injuries.

PMID- 18723469
TI  - More on benzocaine-induced methemoglobinemia.

PMID- 18723471
TI  - Genetic analysis in patients with Kallmann syndrome: coexistence of mutations in
      prokineticin receptor 2 and KAL1.
AB  - Kallmann syndrome (KS) is characterized by the association of hypogonadotropic
      hypogonadism and anosmia or hyposmia. To date, 4 different genes have been
      identified as responsible for the presence of KS; however, in many cases no
      mutations have been found in any of these genes. Herein, we report the molecular
      findings regarding the analysis of fibroblast growth factor receptor 1 (FGFR1),
      prokineticin receptor 2 (PROKR2), and prokineticin (PROK2) in patients with KS.
      Twenty-four patients with KS were studied in whom mutations in KAL1 had been
      investigated previously. Polymerase chain reaction products from FGFR1, PROKR2,
      and PROK2 were sequenced and mutations were sought in the open reading frame of
      the 3 genes. Two patients presented a heterozygous T-to-G transversion in exon 2
      (c.518T>G) of the PROKR2, which results in a leucine-to-arginine substitution at
      codon 173. Our results strengthen the hypothesis of possible digenic inheritance
      in some patients with KS. Likewise, our data extend previous reports
      demonstrating that PROKR2 plays a role in the etiology of this syndrome.

PMID- 18723470
TI  - A single base pair mutation encoding a premature stop codon in the MIS type II
      receptor is responsible for canine persistent Mullerian duct syndrome.
AB  - Mullerian inhibiting substance (MIS), a secreted glycoprotein in the transforming
      growth factor-beta family of growth factors, mediates regression of the Mullerian
      ducts during embryonic sex differentiation in males. In persistent Mullerian duct
      syndrome (PMDS), rather than undergoing involution, the Mullerian ducts persist
      in males, giving rise to the uterus, fallopian tubes, and upper vagina. Genetic
      defects in MIS or its receptor (MISRII) have been identified in patients with
      PMDS. The phenotype in the canine model of PMDS derived from the miniature
      schnauzer breed is strikingly similar to that of human patients. In this model,
      PMDS is inherited as a sex-limited autosomal recessive trait. Previous studies
      indicated that a defect in the MIS receptor or its downstream signaling pathway
      was likely to be causative of the canine syndrome. In this study, the canine PMDS
      phenotype and clinical sequelae are described in detail. Affected and unaffected
      members of this pedigree are genotyped, identifying a single base pair
      substitution in MISRII that introduces a stop codon in exon 3. The homozygous
      mutation terminates translation at 80 amino acids, eliminating much of the
      extracellular domain and the entire transmembrane and intracellular signaling
      domains. Findings in this model could enable insights to be garnered from
      correlation of detailed clinical descriptions with molecular defects, which are
      not otherwise possible in the human syndrome.

PMID- 18723472
TI  - Various physical stress factors on rat sperm motility, integrity of acrosome, and
      plasma membrane.
AB  - The objective of this study was to determine the effects of various physical
      interventions such as centrifugation regimes, Percoll gradient separation, and
      repeated pipetting on various viability parameters of epididymal sperm of Fischer
      344 (F-344) and Sprague-Dawley (SD) rat strains. Three experiments were
      conducted. In experiment 1, sperm motility and acrosomal and membrane integrity
      were compared after exposing sperm samples to 200, 400, 600, and 800 x g
      centrifugal forces for 5, 10, or 15 minutes. In experiment 2, sperm motility and
      acrosomal and membrane integrity were compared after passing them through a
      Percoll separation using centrifugal forces of 600, 800, 1000, and 1200 x g for
      either 15 or 30 minutes. In experiment 3, the effect of repeated pipetting (2, 4,
      6, 8, and 10 times) on motility and membrane integrity of rat sperm was compared
      with that on mouse, ram, bull, and boar sperm. The results revealed that both F
      344 and SD rat sperm motility and membrane integrity were significantly affected
      by centrifugation (P < .05). The acrosomal integrity of SD rat sperm was affected
      after using 800 x g centrifugation force for 10 or 15 minutes (P < .05), whereas
      F-344 rat sperm acrosomal integrity was not affected by any centrifugation
      regimes (P > .05). Sperm from SD rats also had higher motility and membrane
      integrity loss than did sperm from F-344 rats after centrifugation and pipetting
      (P < .05). Percoll gradient separation did not cause significant motility loss or
      acrosomal damage to either F-344 or SD sperm (P > .05). Repeated pipetting had a
      dramatic adverse effect on both rat and mouse sperm motility (P < .05) as
      compared with sperm from bull, boar, and ram, which were not affected at all (P >
      .05). These data suggest that rat sperm have unique properties that need to be
      considered during centrifugation, Percoll gradient separation, and pipetting
      procedures.

PMID- 18723474
TI  - Let's validate those cell lines.

PMID- 18723473
TI  - Silencing of Abcd1 and Abcd2 genes sensitizes astrocytes for inflammation:
      implication for X-adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy is a metabolic disorder arising from a
      mutation/deletion in the ABCD1 gene, leading to a defect in the peroxisomal
      adrenoleukodystrophy protein (ALDP), which inhibits the oxidation of very long
      chain fatty acids (VLCFAs). Thus, these VLCFAs accumulate. In a cerebral form of
      ALD (cALD), VLCFA accumulation induces neuroinflammation that leads to loss of
      oligodendrocytes and myelin, which ultimately shortens the lifespan. To establish
      a relationship between the metabolic disease and inflammatory disease induction,
      we document that small interfering RNA (siRNA)-mediated silencing of Abcd1 (ALDP)
      and Abcd2 [adrenoleukodystrophy-related protein (ALDRP)] genes in mice primary
      astrocyte cultures resulted in accumulation of VLCFA and induction of an
      inflammatory response characteristic of human cALD. Correction of the metabolic
      defect using monoenoic FAs in Abcd1/Abcd2-silenced cultured astrocytes decreased
      inducible nitric oxide synthase and inflammatory cytokine expression, suggesting
      a link between VLCFA accumulation and inflammation. The inflammatory response was
      found to be mediated by transcription factors NF-kappaB, AP-1, and C/EBP in
      Abcd1/Abcd2-silenced mouse primary astrocytes. Although mechanisms of VLCFA
      mediated induction of the inflammatory response have been investigated here in
      vitro, the in vivo mediators remain elusive. Our data represent the first study
      to suggest a direct link between the accumulation of VLCFA and the induction of
      inflammatory mediators.

PMID- 18723475
TI  - Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on
      erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo
      pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild
      type mice.
AB  - We tested whether erlotinib hydrochloride (Tarceva, OSI-774), an orally active
      epidermal growth factor receptor tyrosine kinase inhibitor, is a substrate for
      the ATP-binding cassette drug transporters P-glycoprotein (P-gp; MDR1, ABCB1),
      breast cancer resistance protein (BCRP; ABCG2), and multidrug resistance protein
      2 (MRP2; ABCC2) in vitro and whether P-gp and BCRP affect the oral
      pharmacokinetics of erlotinib hydrochloride in vivo. In vitro cell survival, drug
      transport, accumulation, and efflux of erlotinib were done using Madin-Darby
      canine kidney II [MDCKII; wild-type (WT), MDR1, Bcrp1, and MRP2] and LLCPK (WT
      and MDR1) cells and monolayers as well as the IGROV1 and the derived human BCRP
      overexpressing T8 cell lines. In vivo, the pharmacokinetics of erlotinib after
      p.o. and i.p. administration was studied in Bcrp1/Mdr1a/1b(-/-) (triple-knockout)
      and WT mice. In vitro, erlotinib was actively transported by P-gp and BCRP/Bcrp1.
      No active transport of erlotinib by MRP2 was observed. In vivo, systemic exposure
      (P = 0.01) as well as bioavailability of erlotinib after oral administration (5
      mg/kg) were statistically significantly increased in Bcrp1/Mdr1a/1b(-/-) knockout
      mice (60.4%) compared with WT mice (40.0%; P = 0.02). CONCLUSION: Erlotinib is
      transported efficiently by P-gp and BCRP/Bcrp1 in vitro. In vivo, absence of P-gp
      and Bcrp1 significantly affected the oral bioavailability of erlotinib. Possible
      clinical consequences for drug-drug and drug-herb interactions in patients in the
      gut between P-gp/BCRP-inhibiting substrates and oral erlotinib need to be
      addressed.

PMID- 18723476
TI  - Improved tumor targeting of anti-epidermal growth factor receptor Nanobodies
      through albumin binding: taking advantage of modular Nanobody technology.
AB  - The approximately 15-kDa variable domains of camelid heavy-chain-only antibodies
      (called Nanobodies) can easily be formatted as multivalent or multispecific
      single-chain proteins. Because of fast excretion, however, they are less suitable
      for therapy of cancer. In this study, we aimed for improved tumor targeting of a
      bivalent anti-epidermal growth factor receptor (EGFR) Nanobody (alphaEGFR
      alphaEGFR) by fusion to a Nanobody unit binding to albumin (alphaAlb).
      Biodistributions of alphaEGFR-alphaEGFR, alphaEGFR-alphaEGFR-alphaAlb (
      approximately 50 kDa), alphaTNF-alphaTNF-alphaAlb (control, binding tumor
      necrosis factor-alpha), and the approximately 150-kDa anti-EGFR antibody
      cetuximab were compared in A431 xenograft-bearing mice. The proteins were
      radiolabeled with (177)Lu to facilitate quantification. Tumor uptake of (177)Lu
      alphaEGFR-alphaEGFR decreased from 5.0 +/- 1.4 to 1.1 +/- 0.1 %ID/g between 6 and
      72 h after injection. Due to its rapid blood clearance, tumor-to-blood ratios >80
      were obtained within 6 h after injection. Blood clearance became dramatically
      slower and tumor uptake became significantly higher by introduction of alphaAlb.
      Blood levels of alphaEGFR-alphaEGFR-alphaAlb were 21.2 +/- 2.5, 11.9 +/- 0.6, and
      4.0 +/- 1.4 and tumor levels were 19.4 +/- 5.5, 35.2 +/- 7.5, and 28.0 +/- 6.8
      %ID/g at 6, 24, and 72 h after injection, respectively. Tumor uptake was at least
      as high as for cetuximab (15.5 +/- 3.9, 27.1 +/- 7.9, and 25.6 +/- 6.1 %ID/g) and
      significantly higher than for alphaTNF-alphaTNF-alphaAlb. alphaEGFR-alphaEGFR
      alphaAlb showed faster and deeper tumor penetration than cetuximab. These data
      show that simple fusion of alphaEGFR and alphaAlb building blocks results in a
      bifunctional Nanobody format, which seems more favorable for therapy as far as
      pharmacokinetics and tumor deposition are concerned.

PMID- 18723477
TI  - Caspase-2 functions upstream of mitochondria in endoplasmic reticulum stress
      induced apoptosis by bortezomib in human myeloma cells.
AB  - Multiple myeloma is an incurable plasma cell malignancy. The 26S proteasome
      inhibitor, bortezomib, selectively induces apoptosis in multiple myeloma cells;
      however, the mechanism by which this compound acts remains unknown. Here, we,
      using immunoblotting analysis, observed that the expression of BiP, CHOP, and XBP
      1 is up-regulated in bortezomib-induced apoptosis in human multiple myeloma cell
      lines NCI-H929 and RPMI-8226/S, strongly suggesting that endoplasmic reticulum
      (ER) stress response or the unfolded protein response (UPR), a signaling pathway
      activated by the accumulation of unfolded proteins within ER, is initiated. In
      the meantime, we also showed that bortezomib inhibited classic ER stressor
      brefeldin A-induced up-regulation of prosurvival UPR components BiP and XBP-1,
      resulting in increased induction of apoptosis in multiple myeloma cell lines,
      raising the possibility that bortezomib induces apoptosis of multiple myeloma
      cells by means of evoking the severe ER stress but disrupting the prosurvival UPR
      required. Using caspase inhibitors and a RNA interference approach, we finally
      confirmed that bortezomib-triggered apoptosis in multiple myeloma cells is
      dependent on caspase-2 activation, which is associated with ER stress and
      required for release of cytochrome c, breakdown of mitochondrial transmembrane
      potential, and its downstream caspase-9 activation. Taken together, these data
      strongly suggest that caspase-2 can serve as a proximal caspase that functions
      upstream of mitochondrial signaling during ER stress-induced apoptosis by
      bortezomib in multiple myeloma cells.

PMID- 18723478
TI  - Z3, a novel Jak2 tyrosine kinase small-molecule inhibitor that suppresses Jak2
      mediated pathologic cell growth.
AB  - Jak2 tyrosine kinase is essential for animal development and hyperkinetic Jak2
      function has been linked to a host of human diseases. Control of this pathway
      using Jak2-specific inhibitors would therefore potentially serve as a useful
      research tool and/or therapeutic agent. Here, we used a high-throughput program
      called DOCK to predict the ability of 20,000 small molecules to interact with a
      structural pocket adjacent to the ATP-binding site of murine Jak2. One small
      molecule, 2-methyl-1-phenyl-4-pyridin-2-yl-2-(2-pyridin-2-ylethyl)butan-1-one
      (herein designated as Z3), bound to Jak2 with a favorable energy score. Z3
      inhibited Jak2-V617F and Jak2-WT autophosphorylation in a dose-dependent manner
      but was not cytotoxic to cells at concentrations that inhibited kinase activity.
      Z3 selectively inhibited Jak2 kinase function with no effect on Tyk2 or c-Src
      kinase function. Z3 significantly inhibited proliferation of the Jak2-V617F
      expressing, human erythroleukemia cell line, HEL 92.1.7. The Z3-mediated
      reduction in cell proliferation correlated with reduced Jak2 and STAT3 tyrosine
      phosphorylation levels as well as marked cell cycle arrest. Finally, Z3 inhibited
      the growth of hematopoietic progenitor cells isolated from the bone marrow of an
      essential thrombocythemia patient harboring the Jak2-V617F mutation and a
      polycythemia vera patient carrying a Jak2-F537I mutation. Collectively, the data
      suggest that Z3 is a novel specific inhibitor of Jak2 tyrosine kinase.

PMID- 18723479
TI  - Elesclomol induces cancer cell apoptosis through oxidative stress.
AB  - Elesclomol (formerly STA-4783) is a novel small molecule undergoing clinical
      evaluation in a pivotal phase III melanoma trial (SYMMETRY). In a phase II
      randomized, double-blinded, controlled, multi-center trial in 81 patients with
      stage IV metastatic melanoma, treatment with elesclomol plus paclitaxel showed a
      statistically significant doubling of progression-free survival time compared
      with treatment with paclitaxel alone. Although elesclomol displays significant
      therapeutic activity in the clinic, the mechanism underlying its anticancer
      activity has not been defined previously. Here, we show that elesclomol induces
      apoptosis in cancer cells through the induction of oxidative stress. Treatment of
      cancer cells in vitro with elesclomol resulted in the rapid generation of
      reactive oxygen species (ROS) and the induction of a transcriptional gene profile
      characteristic of an oxidative stress response. Inhibition of oxidative stress by
      the antioxidant N-acetylcysteine blocked the induction of gene transcription by
      elesclomol. In addition, N-acetylcysteine blocked drug-induced apoptosis,
      indicating that ROS generation is the primary mechanism responsible for the
      proapoptotic activity of elesclomol. Excessive ROS production and elevated levels
      of oxidative stress are critical biochemical alterations that contribute to
      cancer cell growth. Thus, the induction of oxidative stress by elesclomol
      exploits this unique characteristic of cancer cells by increasing ROS levels
      beyond a threshold that triggers cell death.

PMID- 18723480
TI  - Diallyl trisulfide increases the effectiveness of TRAIL and inhibits prostate
      cancer growth in an orthotopic model: molecular mechanisms.
AB  - Recent studies have shown that naturally occurring compounds can enhance the
      efficacy of chemotherapeutic drugs. The objectives of this study were to
      investigate the molecular mechanisms by which diallyl trisulfide (DATS) enhanced
      the therapeutic potential of tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) in prostate cancer cells in vitro and on orthotopically
      transplanted PC-3 prostate carcinoma in nude mice. DATS inhibited cell viability
      and colony formation and induced apoptosis in PC-3 and LNCaP cells. DATS enhanced
      the apoptosis-inducing potential of TRAIL in PC-3 cells and sensitized TRAIL
      resistant LNCaP cells. Dominant-negative FADD inhibited the synergistic
      interaction between DATS and TRAIL on apoptosis. DATS induced the expression of
      DR4, DR5, Bax, Bak, Bim, Noxa, and PUMA and inhibited expression of Mcl-1, Bcl-2,
      Bcl-X(L), survivin, XIAP, cIAP1, and cIAP2. Oral administration of DATS
      significantly inhibited growth of orthotopically implanted prostate carcinoma in
      BALB/c nude mice compared with the control group, without causing weight loss.
      Cotreatment of mice with DATS and TRAIL was more effective in inhibiting prostate
      tumor growth and inducing DR4 and DR5 expression, caspase-8 activity, and
      apoptosis than either agent alone. DATS inhibited angiogenesis (as measured by
      CD31-positive and factor VIII-positive blood vessels and hypoxia-inducible factor
      1alpha, vascular endothelial growth factor, and interleukin-6 expression) and
      metastasis [matrix metalloproteinase (MMP)-2, MMP-7, MMP-9, and MT-1 MMP
      expression], which were correlated with inhibition in AKT and nuclear factor
      kappaB activation. The combination of DATS and TRAIL was more effective in
      inhibiting markers of angiogenesis and metastasis than either agent alone. These
      data suggest that DATS can be combined with TRAIL for the prevention and/or
      treatment of prostate cancer.

PMID- 18723481
TI  - BH3-only protein mimetic obatoclax sensitizes cholangiocarcinoma cells to
      Apo2L/TRAIL-induced apoptosis.
AB  - Human cholangiocarcinomas evade apoptosis by overexpression of Mcl-1. The drug
      obatoclax (GX15-070) inhibits antiapoptotic members of the Bcl-2 family including
      Mcl-1. The purpose of this study is to determine if obatoclax sensitizes human
      cholangiocarcinoma cells to apoptosis. The human cholangiocarcinoma cell lines,
      KMCH, KMBC, and TFK, were employed for these studies. Protein expression was
      assessed by immunoblot and protein-protein interactions detected by
      coprecipitation of the polypeptide of interest with S-tagged Mcl-1. Activation of
      Bak and Bax was observed by immunocytochemistry with conformation-specific
      antisera. Obatoclax induced minimal apoptosis alone; however, it increased
      apoptosis 3- to 13-fold in all three cancer cell lines when combined with
      Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Obatoclax
      did not alter cellular expression of Bid, Bim, Puma, Noxa, Bak, Bax, Mcl-1, or
      cFLIP. Mcl-1 binding to Bak was readily identified in untreated cells, and this
      association was disrupted by treating the cells with obatoclax. Additionally, Bim
      binding to Mcl-1 was markedly decreased by obatoclax treatment. We also
      identified alterations in Bak and Bax conformation following treatment with
      obatoclax plus Apo2L/TRAIL but not with either Apo2L/TRAIL or obatoclax alone. In
      conclusion, obatoclax releases Bak and Bim from Mcl-1 and sensitizes human
      cholangiocarcinoma cells to Apo2L/TRAIL-induced apoptosis. Obatoclax is a
      potentially promising adjunctive agent for the treatment of this cancer.

PMID- 18723483
TI  - Mitotic catastrophe cell death induced by heat shock protein 90 inhibitor in
      BRCA1-deficient breast cancer cell lines.
AB  - Heat shock protein 90 (Hsp90) is a molecular chaperone involved in folding,
      assembly, maturation, and stabilization of the client proteins that regulate
      survival of malignant cells. As previous reports correlate high Hsp90 expression
      with decreased survival in breast cancer, Hsp90 may be a favorable target for
      investigational therapy in breast cancer. In our study, we have examined the
      response of a panel of both BRCA1-null (UACC 3199, HCC 1937, and MBA-MD-436) and
      BRCA1-wt breast cancer cell lines (MCF-7, MBA-MD-157, and Hs578T) to determine
      the proteins governing response to Hsp90 inhibitor 17-allyloamino-17-demethoxy
      geldanamycin. On treatment with the drug, cells arrested at G(2)-M phase and
      entered aberrant mitosis in a BRCA1-dependent manner. Failure to arrest the cells
      at or before mitosis resulted in formation of micronucleated cells, aberrant
      segregation of chromosomes, microtubule misalignment, and multicentrosomes,
      leading in eventual mitotic catastrophe cell death. Our observations show that
      BRCA1 mediates G(2)-M transition mainly through chek1 on 17-allyloamino-17
      demethoxy-geldanamycin treatment.

PMID- 18723482
TI  - Androgen receptor inactivation contributes to antitumor efficacy of 17{alpha}
      hydroxylase/17,20-lyase inhibitor 3beta-hydroxy-17-(1H-benzimidazole-1
      yl)androsta-5,16-diene in prostate cancer.
AB  - We previously reported that our novel compound 3beta-hydroxy-17-(1H-benzimidazole
      1-yl)androsta-5,16-diene (VN/124-1) is a potent 17alpha-hydroxylase/17,20-lyase
      (CYP17) inhibitor/antiandrogen and strongly inhibits the formation and
      proliferation of human prostate cancer LAPC4 tumor xenografts in severe combined
      immunodeficient mice. In this study, we report that VN/124-1 and other novel
      CYP17 inhibitors also cause down-regulation of androgen receptor (AR) protein
      expression in vitro and in vivo. This mechanism of action seems to contribute to
      their antitumor efficacy. We compared the in vivo antitumor efficacy of VN/124-1
      with that of castration and a clinically used antiandrogen, Casodex, and show
      that VN/124-1 is more potent than castration in the LAPC4 xenograft model.
      Treatment with VN/124-1 (0.13 mmol/kg twice daily) was also very effective in
      preventing the formation of LAPC4 tumors (6.94 versus 2410.28 mm(3) in control
      group). VN/124-1 (0.13 mmol/kg twice daily) and VN/124-1 (0.13 mmol/kg twice
      daily) + castration induced regression of LAPC4 tumor xenografts by 26.55% and
      60.67%, respectively. Treatments with Casodex (0.13 mmol/kg twice daily) or
      castration caused significant tumor suppression compared with control.
      Furthermore, treatment with VN/124-1 caused marked down-regulation of AR protein
      expression, in contrast to treatments with Casodex or castration that caused
      significant up-regulation of AR protein expression. The results suggest that
      VN/124-1 acts by several mechanisms (CYP17 inhibition, competitive inhibition,
      and down-regulation of the AR). These actions contribute to inhibition of the
      formation of LAPC4 tumors and cause regression of growth of established tumors.
      VN/124-1 is more efficacious than castration in the LAPC4 xenograft model,
      suggesting that the compound has potential for the treatment of prostate cancer.

PMID- 18723484
TI  - SN52, a novel nuclear factor-kappaB inhibitor, blocks nuclear import of RelB:p52
      dimer and sensitizes prostate cancer cells to ionizing radiation.
AB  - The activation of nuclear factor-kappaB (NF-kappaB) is thought to protect cancer
      cells against therapy-induced cytotoxicity. RelB, a member of the NF-kappaB
      family in the alternative pathway, is uniquely expressed at a high level in
      prostate cancer with high Gleason scores. Here, we show that ionizing radiation
      (IR) enhances nuclear import of RelB, leading to up-regulation of its target
      gene, manganese superoxide dismutase (MnSOD), and renders prostate cancer cells
      resistant to IR. To selectively block RelB nuclear import, we designed a cell
      permeable SN52 peptide, a variant of the SN50 peptide that has been shown to
      block nuclear import of NF-kappaB family members in the classic pathway.
      Inhibition of IR-induced NF-kappaB activation by SN50 and SN52 was achieved by
      selectively interrupting the association of p50 and p52 with nuclear import
      factors importin-alpha1 and importin-beta1. Importantly, SN52 seems to be more
      efficient for radiosensitization of prostate cancer cells at clinically relevant
      radiation doses and has less cytotoxicity to normal prostate epithelial cells
      compared with the toxicity observed with SN50. These results suggest that
      targeting the alternative pathway is a promising approach to selectively
      radiosensitize prostate cancers and that SN52 may serve as a prototype biological
      agent for sensitizing prostate cancers to clinically relevant doses of IR.

PMID- 18723485
TI  - Jadomycin B, an Aurora-B kinase inhibitor discovered through virtual screening.
AB  - Aurora kinases have emerged as promising targets for cancer therapy because of
      their critical role in mitosis. These kinases are well-conserved in all
      eukaryotes, and IPL1 gene encodes the single Aurora kinase in budding yeast. In a
      virtual screening attempt, 22 compounds were identified from nearly 15,000
      microbial natural products as potential small-molecular inhibitors of human
      Aurora-B kinase. One compound, Jadomycin B, inhibits the growth of ipl1-321
      temperature-sensitive mutant more dramatically than wild-type yeast cells,
      raising the possibility that this compound is an Aurora kinase inhibitor. Further
      in vitro biochemical assay using purified recombinant human Aurora-B kinase shows
      that Jadomycin B inhibits Aurora-B activity in a dose-dependent manner. Our
      results also indicate that Jadomycin B competes with ATP for the kinase domain,
      which is consistent with our docking prediction. Like other Aurora kinase
      inhibitors, Jadomycin B blocks the phosphorylation of histone H3 on Ser10 in
      vivo. We also present evidence suggesting that Jadomycin B induces apoptosis in
      tumor cells without obvious effects on cell cycle. All the results indicate that
      Jadomycin B is a new Aurora-B kinase inhibitor worthy of further investigation.

PMID- 18723486
TI  - Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule
      inhibitor of checkpoint kinase 1.
AB  - Checkpoints are present in all phases of the cell cycle and are regarded as the
      gatekeepers maintaining the integrity of the genome. Many conventional agents
      used to treat cancer impart damage to the genome and activate cell cycle
      checkpoints. Many tumors are defective in the tumor suppressor p53 and therefore
      lack a functional G(1) checkpoint. In these tumors, however, the S-G(2)
      checkpoints remain intact and, in response to DNA damage, arrest cell cycle
      progression allowing time for DNA repair. Checkpoint kinase 1 (Chk1) is a key
      element in the DNA damage response pathway and plays a crucial role in the S-G(2)
      phase checkpoints. Inhibiting Chk1 represents a therapeutic strategy for creating
      a "synthetic lethal" response by overriding the last checkpoint defense of tumor
      cells against the lethal damage induced by DNA-directed chemotherapeutic agents.
      Chk1 inhibition is consistent with emerging targeted therapies aiming to exploit
      molecular differences between normal and cancer cells. Adding a Chk1 inhibitor to
      DNA-damaging cytotoxic therapy selectively targets tumors with intrinsic
      checkpoint defects while minimizing toxicity in checkpoint-competent normal
      cells. PF-00477736 was identified as a potent, selective ATP-competitive small
      molecule inhibitor that inhibits Chk1 with a K(i) of 0.49 nM. PF-00477736
      abrogates cell cycle arrest induced by DNA damage and enhances cytotoxicity of
      clinically important chemotherapeutic agents, including gemcitabine and
      carboplatin. In xenografts, PF-00477736 enhanced the antitumor activity of
      gemcitabine in a dose-dependent manner. PF-00477736 combinations were well
      tolerated with no exacerbation of side effects commonly associated with cytotoxic
      agents.

PMID- 18723487
TI  - New insights into the pharmacology and cytotoxicity of gemcitabine and 2',2'
      difluorodeoxyuridine.
AB  - In a clinical study with oral gemcitabine (2',2'-difluorodeoxycytidine, dFdC),
      2',2'-difluorodeoxyuridine (dFdU) was extensively formed and accumulated after
      multiple oral dosing. Here, we have investigated the in vitro cytotoxicity,
      cellular uptake, efflux, biotransformation, and nucleic acid incorporation of
      dFdC and dFdU. Short-term and long-term cytotoxicity assays were used to assess
      the cytotoxicity of dFdC and dFdU in human hepatocellular carcinoma HepG2, human
      lung carcinoma A549, and Madin-Darby canine kidney cell lines transfected with
      the human concentrative or equilibrative nucleoside transporter 1 (hCNT1 or
      hENT1), or empty vector. Radiolabeled dFdC and dFdU were used to determine
      cellular uptake, efflux, biotransformation, and incorporation into DNA and RNA.
      The compounds dFdC, dFdU, and their phosphorylated metabolites were quantified by
      high-performance liquid chromatography with UV and radioisotope detection. dFdU
      monophosphate, diphosphate, and triphosphate (dFdU-TP) were formed from dFdC and
      dFdU. dFdU-TP was incorporated into DNA and RNA. The area under the intracellular
      concentration-time curve of dFdC-TP and dFdU-TP and their extent of incorporation
      into DNA and RNA inversely correlated with the IC(50) of dFdC and dFdU,
      respectively. The cellular uptake and cytotoxicity of dFdU were significantly
      enhanced by hCNT1. dFdU inhibited cell cycle progression and its cytotoxicity
      significantly increased with longer duration of exposure. dFdU is taken up into
      cells with high affinity by hCNT1 and phosphorylated to its dFdU-TP metabolite.
      dFdU-TP is incorporated into DNA and RNA, which correlated with dFdU
      cytotoxicity. These data provide strong evidence that dFdU can significantly
      contribute to the cytotoxicity of dFdC.

PMID- 18723488
TI  - IRC-083927 is a new tubulin binder that inhibits growth of human tumor cells
      resistant to standard tubulin-binding agents.
AB  - Tubulin is a validated target for antitumor drugs. However, the effectiveness of
      these microtubule-interacting agents is limited by the fact that they are
      substrates for drug efflux pumps (P-glycoprotein) and/or by the acquisition of
      point mutations in tubulin residues important for drug-tubulin binding. To bypass
      these resistance systems, we have identified and characterized a novel synthetic
      imidazole derivative IRC-083927, which inhibits the tubulin polymerization by a
      binding to the colchicine site. IRC-083927 inhibits in vitro cell growth of human
      cancer cell lines in the low nanomolar range. More interesting, it remains highly
      active against cell lines resistant to microtubule-interacting agents (taxanes,
      Vinca alkaloids, or epothilones). Such resistances are due to the presence of
      efflux pumps (NCI-H69/LX4 resistant to navelbine and paclitaxel) and/or the
      presence of mutations on beta-tubulin and on alpha-tubulin and beta-tubulin
      (A549.EpoB40/A549.EpoB480 resistant to epothilone B or paclitaxel). IRC-083927
      displayed cell cycle arrest in G(2)-M phase in tumor cells, including in the drug
      resistant cells. In addition, IRC-083927 inhibited endothelial cell proliferation
      in vitro and vessel formation in the low nanomolar range supporting an
      antiangiogenic behavior. Finally, chronic oral treatment with IRC-083927 (5
      mg/kg) inhibits the growth of two human tumor xenografts in nude mice (C33-A,
      human cervical cancer and MDA-MB-231, human hormone-independent breast cancer).
      Together, the antitumor effects induced by IRC-083927 on tumor models resistant
      to tubulin agents support further investigations to fully evaluate its potential
      for the treatment of advanced cancers, particularly those resistant to current
      clinically available drugs.

PMID- 18723489
TI  - Anticancer steroid sulfatase inhibitors: synthesis of a potent fluorinated second
      generation agent, in vitro and in vivo activities, molecular modeling, and
      protein crystallography.
AB  - An improved steroid sulfatase inhibitor was prepared by replacing the N-propyl
      group of the second-generation steroid-like inhibitor (2) with a N-3,3,3
      trifluoropropyl group to give (10). This compound is 5-fold more potent in vitro,
      completely inhibits rat liver steroid sulfatase activity after a single oral dose
      of 0.5 mg/kg, and exhibits a significantly longer duration of inhibition over
      (2). These biological properties are attributed to the increased lipophilicity
      and metabolic stability of (10) rendered by its trifluoropropyl group and also
      the potential H-bonding between its fluorine atom(s) and Arg(98) in the active
      site of human steroid sulfatase. Like other sulfamates, (10) is expected to be
      sequestered, and transported by, erythrocytes in vivo because it inhibits human
      carbonic anhydrase II (hCAII) potently (IC(50), 3 nmol/L). A congener (4), which
      possesses a N-(pyridin-3-ylmethyl) substituent, is even more active (IC(50), 0.1
      nmol/L). To rationalize this, the hCAII-(4) adduct, obtained by
      cocrystallization, reveals not only the sulfamate group and the backbone of (4)
      interacting with the catalytic site and the associated hydrophobic pocket,
      respectively, but also the potential H-bonding between the N-(pyridin-3-ylmethyl)
      group and Nepsilon(2) of Gln(136). Like (2), both (10) and its phenolic precursor
      (9) are non-estrogenic using a uterine weight gain assay. In summary, a highly
      potent, long-acting, and nonestrogenic steroid sulfatase inhibitor was designed
      with hCAII inhibitory properties that should positively influence in vivo
      behavior. Compound (10) and other related inhibitors of this structural class
      further expand the armory of steroid sulfatase inhibitors against hormone
      dependent breast cancer.

PMID- 18723490
TI  - Targeting tumor cells expressing p53 with a water-soluble inhibitor of Hdm2.
AB  - The tumor suppressor protein p53 is a potent inducer of apoptosis in transformed
      cells. Hdm2 is an ubiquitin ligase (E3) that acts as a major regulator of p53 by
      promoting its ubiquitylation and proteasomal degradation. For this reason,
      inhibiting the E3 activity of Hdm2 has been proposed as a therapeutic approach
      for cancers expressing wild-type p53. We previously identified a family of small
      molecules (HLI98s, 7-nitro-10-aryl-5-deazaflavins) that inhibit the E3 activity
      of Hdm2, increase cellular p53, and selectively kill transformed cells expressing
      wild-type p53. However, issues of both potency and solubility in aqueous solution
      limit the utility of the HLI98s. Here, we report that a highly soluble derivative
      of the HLI98s, which has a 5-dimethylaminopropylamino side chain but lacks the 10
      aryl group (HLI373), has greater potency than the HLI98s in stabilizing Hdm2 and
      p53, activating p53-dependent transcription, and inducing cell death.
      Furthermore, we show that HLI373 is effective in inducing apoptosis of several
      tumor cells lines that are sensitive to DNA-damaging agents. These results
      suggest that HLI373 could serve as a potential lead for developing cancer
      therapeutics based on inhibition of the ubiquitin ligase activity of Hdm2.

PMID- 18723491
TI  - High-content imaging characterization of cell cycle therapeutics through in vitro
      and in vivo subpopulation analysis.
AB  - Although the cycling of eukaryotic cells has long been a primary focus for cancer
      therapeutics, recent advances in imaging and data analysis allow even further
      definition of cellular events as they occur in individual cells and cellular
      subpopulations in response to treatment. High-content imaging (HCI) has been an
      effective tool to elucidate cellular responses to a variety of agents; however,
      these data were most frequently observed as averages of the entire captured
      population, unnecessarily decreasing the resolution of each assay. Here, we
      dissect the eukaryotic cell cycle into individual cellular subpopulations using
      HCI in conjunction with unsupervised K-means clustering. We generate distinct
      phenotypic fingerprints for each major cell cycle and mitotic compartment and use
      those fingerprints to screen a library of 310 commercially available
      chemotherapeutic agents. We determine that the cell cycle arrest phenotypes
      caused by these agents are similar to, although distinct from, those found in
      untreated cells and that these distinctions frequently suggest the mechanism of
      action. We then show via subpopulation analysis that these arrest phenotypes are
      similar in both mouse models and in culture. HCI analysis of cell cycle using
      data obtained from individual cells under a broad range of research conditions
      and grouped into cellular subpopulations represents a powerful method to discern
      both cellular events and treatment effects. In particular, this technique allows
      for a more accurate means of assessing compound selectivity and leads to more
      meaningful comparisons between so-called targeted therapeutics.

PMID- 18723492
TI  - Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for
      adjuvant therapy in pancreatic cancer.
AB  - Pancreatic adenocarcinoma confers one of the highest mortality rates in malignant
      human tumors with very poor prognosis. Because as yet no treatments are available
      that produce a substantial survival benefit for this fatal neoplasia, new
      therapeutic concepts are urgently required to support cancer standard treatment.
      In search of tumor-associated gangliosides with therapeutic background, we probed
      a random collection of cancerous and adjacent normal postoperative tissue samples
      from 38 patients for the expression of CD75s- and iso-CD75s-gangliosides. We
      exhaustively analyzed the expression of CD75s-1-ganglioside (IV(6)Neu5Ac-nLc4Cer)
      and structurally closely related iso-CD75s-1-ganglioside (IV(3)Neu5Ac-nLc4Cer) by
      means of immunohistology of cryosections and semiquantitative TLC of tissue lipid
      extracts combined with mass spectrometry. CD75s-1- and iso-CD75s-1-ganglioside
      showed an elevated expression in 42% and 66% of the tumors, respectively,
      indicating a significant association with neoplastic transformation (P = 0.001).
      Thus, increased expression of CD75s-1- and iso-CD75s-1-gangliosides renders these
      cell surface molecules promising candidates for oncologic applications. Further
      statistical analysis revealed a significant enhancement of CD75s-1-ganglioside in
      the group of less differentiated tumors (grade >2) suggesting this ganglioside as
      a potential marker for poor differentiation. The CD75s-specific antitumor drug
      rViscumin, which represents the recombinant counterpart of the ribosome
      inactivating lectin viscumin, has successfully passed clinical phase I trials and
      provides an opportunity for treating pancreatic cancer. Consequently, if an
      enhanced expression is existent in malignant tissues, we propose the targeting of
      CD75s-gangliosides with rViscumin as a novel potential strategy in adjuvant
      treatment of pancreatic malignancies.

PMID- 18723493
TI  - Autophagy inhibition enhances anthocyanin-induced apoptosis in hepatocellular
      carcinoma.
AB  - Anthocyanins extracted from the berries of Phillyrea latifolia L., Pistacia
      lentiscus L., and Rubia peregrina L., three evergreen shrubs widely distributed
      in the Mediterranean area, were examined for their antioxidant and anticancer
      activity. The P. lentiscus anthocyanins showed the highest H(2)O(2) and 1,1
      diphenyl-2-picryl-hydrazil radical scavenging effects, indicating that these
      compounds can be considered as an alternative source of natural antioxidants for
      food and pharmaceutical products. Here, we also report a novel function of
      anthocyanins: the induction of autophagy, a process of subcellular turnover
      involved in carcinogenesis. Autophagy was characterized by the up-regulation of
      eIF2alpha, an autophagy inducer, and down-regulation of mTOR and Bcl-2, two
      autophagy inhibitors. This led to the enhanced expression of LC3-II, an
      autophagosome marker in mammals, and monodansylcadaverine incorporation into
      autolysosomes. Anthocyanin-induced autophagy switched to apoptosis, as shown by
      the activation of Bax, cytochrome c and caspase 3, terminal deoxynucleotide
      transferase-mediated dUTP nick-end labeling-positive fragmented nuclei, and cells
      with sub-G(1) DNA content, which were prevented by z-VAD. Inhibition of autophagy
      by either 3-methyladenine or Atg5 small interfering RNA enhanced anthocyanin
      triggered apoptosis. This provided evidence that autophagy functions as a
      survival mechanism in liver cancer cells against anthocyanin-induced apoptosis
      and a rationale for the use of autophagy inhibitors in combination with dietary
      chemopreventive agents.

PMID- 18723494
TI  - Anti-CD30 diabody-drug conjugates with potent antitumor activity.
AB  - Anti-CD30 diabodies were engineered with two cysteine mutations for site-specific
      drug conjugation in each chain of these homodimeric antibody fragments. Diabodies
      were conjugated with approximately 4 equivalents of the anti-tubulin drugs,
      monomethyl auristatin E or F, via a protease-cleavable dipeptide linker, to
      create the conjugates, diabody-vcE4 and diabody-vcF4, respectively. Diabody
      conjugation had only minor (<3-fold) effects on antigen binding. Diabody-vcF4 was
      potently cytotoxic against the antigen-positive cell lines, Karpas-299 (34 pmol/L
      IC(50)) and L540cy (22 pmol/L IC(50)), and was 8- and 21-fold more active than
      diabody-vcE4 against these cell lines, respectively. Clearance of diabody-vcF4
      (99-134 mL/d/kg) was 5-fold slower than for the nonconjugated diabody in naive
      severe combined immunodeficient mice. Diabody-vcF4 had potent and dose-dependent
      antitumor activity against established Karpas-299 xenografts and gave durable
      complete responses at well-tolerated doses. Biodistribution experiments with
      diabody-[(3)H]-vcF4 (0.72-7.2 mg/kg) in tumor-bearing mice showed a dose
      dependent increase in total auristatin accumulation in tumors (< or =520 nmol/L)
      and decrease in relative auristatin accumulation (< or =8.1 %ID/g), with peak
      localization at 4 to 24 h after dosing. Diabody-vcF4 had approximately 4-fold
      lower cytotoxic activity than the corresponding IgG1-vcF4 conjugate in vitro. A
      similar potency difference was observed in vivo despite 25- to 34-fold faster
      clearance of diabody-vcF4 than IgG1-vcF4. This may reflect that dose-escalated
      diabody-vcF4 can surpass IgG1-vcF4 in auristatin delivery to tumors, albeit with
      higher auristatin exposure to some organs including kidney and liver. Diabody
      drug conjugates can have potent antitumor activity at well-tolerated doses and
      warrant further optimization for cancer therapy.

PMID- 18723495
TI  - Cellular commitment to reentry into the cell cycle after stalled DNA is
      determined by site-specific phosphorylation of Chk1 and PTEN.
AB  - In this study, we show that depletion of Chk1 by small interfering RNA (siRNA)
      results in failure of reentry to the cell cycle after DNA replication has been
      stalled by exposure to hydroxyurea (HU). Casein kinase II (CKII) is degraded in
      these cells in a proteasome-dependent manner, resulting in decreased
      phosphorylation and PTEN levels. We show that phosphorylation of Chk1 at Ser(317)
      but not at Ser(345) is required for phosphorylation of PTEN at Thr(383) by CKII,
      making cell cycle reentry after HU treatment possible. Like Chk1 depletion, loss
      of PTEN due to siRNA is followed by inability to return to the cell cycle
      following HU. In Chk1-siRNA cells, reintroduction of wild-type PTEN but not PTEN
      T383A restores the ability of the cell to reenter the G(2)-M phase of the cell
      cycle after stalled DNA replication. We conclude that, in response to stalled DNA
      replication, Chk1 is phosphorylated at Ser(317) by ATR resulting in stabilization
      of CKII, which in turn leads to phosphorylation of PTEN at Thr(383).

PMID- 18723496
TI  - Optimization of antibody binding to FcgammaRIIa enhances macrophage phagocytosis
      of tumor cells.
AB  - The contribution of Fc-mediated effector functions to the therapeutic efficacy of
      some monoclonal antibodies has motivated efforts to enhance interactions with
      Fcgamma receptors (FcgammaR). Although an early goal has been enhanced
      FcgammaRIIIa binding and natural killer (NK) cell antibody-dependent cell
      mediated cytotoxicity (ADCC), other relevant cell types such as macrophages are
      dependent on additional activating receptors such as FcgammaRIIa. Here, we
      describe a set of engineered Fc variants with diverse FcgammaR affinities,
      including a novel substitution G236A that provides selectively enhanced binding
      to FcgammaRIIa relative to FcgammaRIIb. Variants containing this substitution
      have up to 70-fold greater FcgammaRIIa affinity and 15-fold improvement in
      FcgammaRIIa/FcgammaRIIb ratio and mediate enhanced phagocytosis of antibody
      coated target cells by macrophages. Specific double and triple combination
      variants with this substitution are simultaneously capable of exhibiting high NK
      mediated ADCC and high macrophage phagocytosis. In addition, we have used this
      unique set of variants to quantitatively probe the relative contributions of
      individual FcgammaR to effector functions mediated by NK cells and macrophages.
      These experiments show that FcgammaRIIa plays the most influential role for
      macrophages and, surprisingly, that the inhibitory receptor FcgammaRIIb has
      little effect on effector function. The enhancements in phagocytosis described
      here provide the potential to improve the performance of therapeutic antibodies
      targeting cancers.

PMID- 18723497
TI  - Adenoviral endoplasmic reticulum-targeted mda-7/interleukin-24 vector enhances
      human cancer cell killing.
AB  - We developed several adenoviral vectors designed to target MDA-7 expression to
      different subcellular compartments [endoplasmic reticulum (ER), mitochondria,
      nucleus, and cytosol] and evaluated their ability to enhance apoptosis.
      Adenoviral ER-targeted mda-7/interleukin-24 vector (Ad-ER-mda7) selectively and
      effectively inhibited the growth and proliferation of lung (A549 and H1299) and
      esophageal (Seg1 and Bic1) cancer cells by enhancing cell killing. Both Ad-mda7
      and Ad-ER-mda7 activated a novel pathway of ER stress-induced apoptosis
      characterized by unregulated expression of phosphorylated JNK, phosphorylated c
      Jun, and phosphorylated RNA-dependent protein kinase. Caspase-4 activation
      mediated Ad-mda7- and Ad-ER-mda7-induced cell death. In addition, Ad-mda7- and Ad
      ER-mda7-mediated growth inhibition correlated with activation of ER molecular
      markers RNA-dependent protein kinase and JNK both in vitro (in Ad-mda7- or Ad-ER
      mda7-treated lung cancer cells) and in vivo. These findings suggest that vectors
      targeting the ER (Ad-ER-mda7) may be more effective in cancer gene therapy
      possibly through more effective induction or ER stress pathways.

PMID- 18723498
TI  - Human endothelial precursor cells express tumor endothelial marker
      1/endosialin/CD248.
AB  - Angiogenesis occurs during normal physiologic processes as well as under
      pathologic conditions such as tumor growth. Serial analysis of gene expression
      profiling revealed genes [tumor endothelial markers (TEM)] that are overexpressed
      in tumor endothelial cells compared with normal adult endothelial cells. Because
      blood vessel development of malignant tumors under certain conditions may include
      endothelial precursor cells (EPC) recruited from bone marrow, we investigated TEM
      expression in EPC. The expression of TEM1 or endosialin (CD248) and other TEM has
      been discovered in a population of vascular endothelial growth factor receptor
      2+/CD31+/CD45-/VE-cadherin+ EPC derived from human CD133+/CD34+ cells. EPC share
      some properties with fully differentiated endothelial cells from normal tissue,
      yet reverse transcription-PCR and flow cytometry reveal that EPC express higher
      levels of endosialin at the molecular and protein levels. The elevated expression
      of endosialin in EPC versus mature endothelial cells suggests that endosialin is
      involved in the earlier stages of tumor angiogenesis. Anti-endosialin antibodies
      inhibited EPC migration and tube formation in vitro. In vivo,
      immunohistochemistry indicated that human EPC continued to express endosialin
      protein in a Matrigel plug angiogenesis assay established in nude mice. Anti
      endosialin antibodies delivered systemically at 25 mg/kg were also able to
      inhibit circulating murine EPC in nude mice bearing s.c. SKNAS tumors. EPC and
      bone marrow-derived cells have been shown previously to incorporate into
      malignant blood vessels in some instances, yet they remain controversial in the
      field. The data presented here on endothelial genes that are up-regulated in
      tumor vasculature and in EPC support the hypothesis that the angiogenesis process
      in cancer can involve EPC.

PMID- 18723499
TI  - Tumor necrosis factor-alpha-induced accentuation in cryoinjury: mechanisms in
      vitro and in vivo.
AB  - Cryosurgical treatment of solid cancer can be greatly assisted by further
      translation of our finding that a cytokine adjuvant tumor necrosis factor-alpha
      (TNF-alpha) can achieve complete cancer destruction out to the intraoperatively
      imaged iceball edge (-0.5 degrees C) over the current clinical recommendation of
      reaching temperatures lower than -40 degrees C. The present study investigates
      the cellular and tissue level dose dependency and molecular mechanisms of TNF
      alpha-induced enhancement in cryosurgical cancer destruction. Microvascular
      endothelial MVEC and human prostate cancer LNCaP Pro 5 (LNCaP) cells were frozen
      as monolayers in the presence of TNF-alpha. Normal skin and LNCaP tumor grown in
      a nude mouse model were also frozen at different TNF-alpha doses. Molecular
      mechanisms were investigated by using specific inhibitors to block nuclear factor
      kappaB-mediated inflammatory or caspase-mediated apoptosis pathways. The amount
      of cryoinjury increased in a dose-dependent manner with TNF-alpha both in vitro
      and in vivo. MVEC were found to be more cryosensitive than LNCaP cells in both
      the presence and the absence of TNF-alpha. The augmentation in vivo was
      significantly greater than that in vitro, with complete cell death up to the
      iceball edge in tumor tissue at local TNF-alpha doses greater than 200 ng. The
      inhibition assays showed contrasting results with caspase-mediated apoptosis as
      the dominant mechanism in MVEC in vitro and nuclear factor-kappaB-mediated
      inflammatory mechanisms within the microvasculatures the dominant mechanism in
      vivo. These results suggest the involvement of endothelial-mediated injury and
      inflammation as the critical mechanisms in cryoinjury and the use of vascular
      targeting molecules such as TNF-alpha to enhance tumor killing and achieve the
      clinical goal of complete cell death within an iceball.

PMID- 18723500
TI  - Fatty acid synthase inhibition results in a magnetic resonance-detectable drop in
      phosphocholine.
AB  - Expression of fatty acid synthase (FASN), the key enzyme in de novo synthesis of
      long-chain fatty acids, is normally low but increases in cancer. Consequently,
      FASN is a novel target for cancer therapy. However, because FASN inhibitors can
      lead to tumor stasis rather than shrinkage, noninvasive methods for assessing
      FASN inhibition are needed. To this end, we combined (1)H, (31)P, and (13)C
      magnetic resonance spectroscopy (MRS) (a) to monitor the metabolic consequences
      of FASN inhibition and (b) to identify MRS-detectable metabolic biomarkers of
      response. Treatment of PC-3 cells with the FASN inhibitor Orlistat for up to 48 h
      resulted in inhibition of FASN activity by 70%, correlating with 74% inhibition
      of fatty acid synthesis. Furthermore, we have determined that FASN inhibition
      results not only in lower phosphatidylcholine levels but also in a 59% drop in
      the phospholipid precursor phosphocholine (PCho). This drop resulted from
      inhibition in PCho synthesis as a result of a reduction in the cellular activity
      of its synthetic enzyme choline kinase. The drop in PCho levels following FASN
      inhibition was confirmed in SKOV-3 ovarian cancer cells treated with Orlistat and
      in MCF-7 breast cancer cells treated with Orlistat as well as cerulenin.
      Combining data from all treated cells, the drop in PCho significantly correlated
      with the drop in de novo synthesized fatty acid levels, identifying PCho as a
      potential noninvasive MRS-detectable biomarker of FASN inhibition in vivo.

PMID- 18723501
TI  - Relaxin treatment of solid tumors: effects on electric field-mediated gene
      delivery.
AB  - Pulsed electric fields have been shown to enhance interstitial transport of
      plasmid DNA (pDNA) in solid tumors in vivo. However, the extent of enhancement is
      still limited partly due to the collagen component in extracellular matrix. To
      this end, effects of collagen remodeling on interstitial electrophoresis were
      investigated by pretreatment of tumor-bearing mice with a recombinant human
      relaxin (rh-Rlx). In the study, two tumor lines (4T1 and B16.F10) were examined
      and implanted s.c. to establish two murine models: dorsal skin-fold chamber (DSC)
      and hind leg. Effects of rh-Rlx on pDNA electrophoresis were measured either
      directly in the DSC model or indirectly in the hind leg model via reporter gene
      expression. It was observed that rh-Rlx treatment reduced collagen levels in the
      hind leg tumors but not in the DSC tumors. The observation correlated with the
      results from electromobility experiments, where rh-Rlx treatment enhanced
      transgene expression in 4T1 hind leg tumors but did not increase the
      electromobility of pDNA in the DSC tumors. In addition, it was observed that pDNA
      binding to collagen could block its diffusion in collagen gel in vitro. These
      observations showed that effects of rh-Rlx on the collagen content depended on
      microenvironment in solid tumors and that rh-Rlx treatment would enhance electric
      field-mediated gene delivery only if it could effectively reduce the collagen
      content in collagen-rich tumors.

PMID- 18723502
TI  - Compartmentalization of phosphatidylinositol 4,5-bisphosphate signaling evidenced
      using targeted phosphatases.
AB  - Phosphatidylinositol 4,5-bisphosphate (PIP(2)) is a prevalent phosphoinositide in
      cell membranes, with important functions in cell signaling and activation. A
      large fraction of PIP(2) associates with the detergent-resistant membrane "raft"
      fraction, but the functional significance of this association remains
      controversial. To measure the properties of raft and nonraft PIP(2) in cell
      signaling, we targeted the PIP(2)-specific phosphatase Inp54p to either the raft
      or nonraft membrane fraction using minimal membrane anchors. Interestingly, we
      observed that targeting Inp54p to the nonraft fraction resulted in an enrichment
      of raft-associated PIP(2) and striking changes in cell morphology, including a
      wortmannin-sensitive increase in cell filopodia and cell spreading. In contrast,
      raft-targeted Inp54p depleted the raft pool of PIP(2) and produced smooth T cells
      void of membrane ruffling and filopodia. Furthermore, raft-targeted Inp54p
      inhibited capping in T cells stimulated by cross-linking the T cell receptor, but
      without affecting the T cell receptor-dependent Ca(2+) flux. Altogether, these
      results provide evidence of compartmentalization of PIP(2)-dependent signaling in
      cell membranes such as predicted by the membrane raft model.

PMID- 18723503
TI  - Chondrocyte aggregation in suspension culture is GFOGER-GPP- and beta1 integrin
      dependent.
AB  - Isolated chondrocytes form aggregates in suspension culture that maintain
      chondrocyte phenotype in a physiological pericellular environment. The molecular
      mechanisms involved in chondrocyte aggregation have not been previously
      identified. Using this novel suspension culture system, we performed mRNA and
      protein expression analysis along with immunohistochemistry for potential cell
      adhesion molecules and extracellular matrix integrin ligands. Inhibition of
      aggregation assays were performed using specific blocking agents. We found that:
      (i) direct cell-cell interactions were not involved in chondrocyte aggregation,
      (ii) chondrocytes in aggregates were surrounded by a matrix rich in collagen II
      and cartilage oligomeric protein (COMP), (iii) aggregation depends on a beta1
      integrin, which binds a triple helical GFOGER sequence found in collagens, (iv)
      integrin alpha10-subunit is the most highly expressed alpha-subunit among those
      tested, including alpha5, in aggregating chondrocytes. Taken together, this body
      of evidence suggests that the main molecular interaction involved in aggregation
      of phenotypically stable chondrocytes is the alpha10beta1-collagen II
      interaction.

PMID- 18723504
TI  - A conserved Cys-loop receptor aspartate residue in the M3-M4 cytoplasmic loop is
      required for GABAA receptor assembly.
AB  - Members of the Cys-loop superfamily of ligand-gated ion channels, which mediate
      fast synaptic transmission in the nervous system, are assembled as
      heteropentamers from a large repertoire of neuronal subunits. Although several
      motifs in subunit N-terminal domains are known to be important for subunit
      assembly, increasing evidence points toward a role for C-terminal domains. Using
      a combination of flow cytometry, patch clamp recording, endoglycosidase H
      digestion, brefeldin A treatment, and analytic centrifugation, we identified a
      highly conserved aspartate residue at the boundary of the M3-M4 loop and the M4
      domain that was required for binary and ternary gamma-aminobutyric acid type A
      receptor surface expression. Mutation of this residue caused mutant and
      partnering subunits to be retained in the endoplasmic reticulum, reflecting
      impaired forward trafficking. Interestingly although mutant and partnering wild
      type subunits could be coimmunoprecipitated, analytic centrifugation studies
      demonstrated decreased formation of pentameric receptors, suggesting that this
      residue played an important role in later steps of subunit oligomerization. We
      thus conclude that C-terminal motifs are also important determinants of Cys-loop
      receptor assembly.

PMID- 18723505
TI  - Protein kinase G-dependent cardioprotective mechanism of phosphodiesterase-5
      inhibition involves phosphorylation of ERK and GSK3beta.
AB  - Sildenafil, a potent inhibitor of phosphodiesterase-5 (PDE-5) induces powerful
      protection against myocardial ischemia-reperfusion injury. PDE-5 inhibition
      increases cGMP levels that activate cGMP-dependent protein kinase (PKG). However,
      the cause and effect relationship of PKG in sildenafil-induced cardioprotection
      and the downstream targets of PKG remain unclear. Adult ventricular myocytes were
      treated with sildenafil and subjected to simulated ischemia and reoxygenation.
      Sildenafil treatment significantly decreased cardiomyocyte necrosis and
      apoptosis. The PKG inhibitors, KT5823, guanosine 3',5'-cyclic
      monophosphorothioate, 8-(4-chloro-phenylthio) (R(p)-8-pCPT-cGMPs), or DT-2
      blocked the anti-necrotic and anti-apoptotic effect of sildenafil. Selective
      knockdown of PKG in cardiomyocytes with adenoviral vector containing short
      hairpin RNA of PKG also abolished sildenafil-induced protection. Furthermore,
      intra-coronary infusion of sildenafil in Langendorff-isolated mouse hearts prior
      to ischemia-reperfusion significantly reduced myocardial infarct size after 20
      min ischemia and 30 min reperfusion, which was abrogated by KT5823. Sildenafil
      significantly increased PKG activity in intact hearts and cardiomyocytes.
      Sildenafil also enhanced the Bcl-2/Bax ratio, phosphorylation of Akt, ERK1/2, and
      glycogen synthase kinase 3beta. All these changes (except Akt phosphorylation)
      were significantly blocked by KT5823 and short hairpin RNA of PKG. These studies
      provide the first evidence for an essential role of PKG in sildenafil-induced
      cardioprotection. Moreover, our results demonstrate that sildenafil activates a
      PKG-dependent novel signaling cascade that involves activation of ERK and
      inhibition of glycogen synthase kinase 3beta leading to cytoprotection.

PMID- 18723506
TI  - The AbetaCs of Abeta-cleaving proteases.
AB  - The amyloid beta-protein (Abeta), which accumulates abnormally in Alzheimer
      disease (AD), is degraded by a diverse set of proteolytic enzymes. Abeta-cleaving
      proteases, largely ignored until only recently, are now known to play a pivotal
      role in the regulation of cerebral Abeta levels and amyloid plaque formation in
      animal models, and accumulating evidence suggests that defective Abeta
      proteolysis may be operative in many AD cases. This review summarizes the growing
      body of evidence supporting the involvement of specific Abeta-cleaving proteases
      in the etiology and potential treatment of AD. Recognition of the importance of
      Abeta degradation to the overall economy of Abeta has revised our thinking about
      the mechanistic basis of AD pathogenesis and identified a novel class of enzymes
      that may serve as both therapeutic targets and therapeutic agents.

PMID- 18723507
TI  - Structural classification of toxic amyloid oligomers.
AB  - Amyloid oligomers are believed to play important causal roles in many types of
      amyloid-related degenerative diseases. Many different laboratories have reported
      amyloid oligomers that differ in size, morphology, toxicity, and method of
      preparation or purification, raising the question of the structural relationships
      among these oligomer preparations. The structural plasticity that has been
      reported to occur in amyloids formed from the same protein sequence indicates
      that it is quite possible that different oligomer preparations may represent
      distinct structural variants. In view of the difficulty in determining the
      precise structure of amyloids, conformation- and epitope-specific antibodies may
      provide a facile means of classifying amyloid oligomer structures. Conformation
      dependent antibodies that recognize generic epitopes that are specifically
      associated with distinct aggregation states of many different amyloid-forming
      sequences indicate that there are at least two fundamentally distinct types of
      amyloid oligomers: fibrillar and prefibrillar oligomers. Classification of
      amyloid oligomers according to their underlying structures may be a more useful
      and rational approach than relying on differences in size and morphology.

PMID- 18723508
TI  - Natural homolog of tRNA synthetase editing domain rescues conditional lethality
      caused by mistranslation.
AB  - AlaXp is a widely distributed (from bacteria to humans) genome-encoded homolog of
      the editing domain of alanyl-tRNA synthetases. Editing repairs the confusion of
      serine and glycine for alanine through clearance of mischarged (with Ser or Gly)
      tRNA(Ala). Because genome-encoded fragments of editing domains of other
      synthetases are scarce, the AlaXp redundancy of the editing domain of alanyl-tRNA
      synthetase is thought to reflect an unusual sensitivity of cells to
      mistranslation at codons for Ala. Indeed, a small defect in the editing activity
      of alanyl-tRNA synthetase is causally linked to neurodegeneration in the mouse.
      Although limited earlier studies demonstrated that AlaXp deacylated mischarged
      tRNA(Ala) in vitro, the significance of this activity in vivo has not been clear.
      Here we describe a bacterial system specifically designed to investigate activity
      of AlaXp in vivo. Serine toxicity, experienced by a strain harboring an editing
      defective alanyl-tRNA synthetase, was rescued by an AlaXp-encoding transgene.
      Rescue was dependent on amino acid residues in AlaXp that are needed for its in
      vitro catalytic activity. Thus, the editing activity per se of AlaXp was
      essential for suppressing mistranslation. The results support the idea that the
      unique widespread distribution of AlaXp arises from the singular difficulties,
      for translation, poised by alanine.

PMID- 18723509
TI  - The organization of LH2 complexes in membranes from Rhodobacter sphaeroides.
AB  - The mapping of the photosynthetic membrane of Rhodobacter sphaeroides by atomic
      force microscopy (AFM) revealed a unique organization of arrays of dimeric
      reaction center-light harvesting I-PufX (RC-LH1-PufX) core complexes surrounded
      and interconnected by light-harvesting LH2 complexes (Bahatyrova, S., Frese, R.
      N., Siebert, C. A., Olsen, J. D., van der Werf, K. O., van Grondelle, R.,
      Niederman, R. A., Bullough, P. A., Otto, C., and Hunter, C. N. (2004) Nature 430,
      1058-1062). However, membrane regions consisting solely of LH2 complexes were
      under-represented in these images because these small, highly curved areas of
      membrane rendered them difficult to image even using gentle tapping mode AFM and
      impossible with contact mode AFM. We report AFM imaging of membranes prepared
      from a mutant of R. sphaeroides, DPF2G, that synthesizes only the LH2 complexes,
      which assembles spherical intracytoplasmic membrane vesicles of approximately 53
      nm diameter in vivo. By opening these vesicles and adsorbing them onto mica to
      form small, < or =120 nm, largely flat sheets we have been able to visualize the
      organization of these LH2-only membranes for the first time. The transition from
      highly curved vesicle to the planar sheet is accompanied by a change in the
      packing of the LH2 complexes such that approximately half of the complexes are
      raised off the mica surface by approximately 1 nm relative to the rest. This
      vertical displacement produces a very regular corrugated appearance of the planar
      membrane sheets. Analysis of the topographs was used to measure the distances and
      angles between the complexes. These data are used to model the organization of
      LH2 complexes in the original, curved membrane. The implications of this
      architecture for the light harvesting function and diffusion of quinones in
      native membranes of R. sphaeroides are discussed.

PMID- 18723510
TI  - A role for GCAP2 in regulating the photoresponse. Guanylyl cyclase activation and
      rod electrophysiology in GUCA1B knock-out mice.
AB  - Cyclic GMP serves as the second messenger in visual transduction, linking photon
      absorption by rhodopsin to the activity of ion channels. Synthesis of cGMP in
      photoreceptors is supported by a pair of retina-specific guanylyl cyclases,
      retGC1 and -2. Two neuronal calcium sensors, GCAP1 and GCAP2, confer Ca(2+)
      sensitivity to guanylyl cyclase activity, but the importance and the contribution
      of each GCAP is controversial. To explore this issue, the gene GUCA1B, coding for
      GCAP2, was disrupted in mice, and the capacity for knock-out rods to regulate
      retGC and generate photoresponses was tested. The knock-out did not compromise
      rod viability or alter outer segment ultrastructure. Levels of retGC1, retGC2,
      and GCAP-1 expression did not undergo compensatory changes, but the absence of
      GCAP2 affected guanylyl cyclase activity in two ways; (a) the maximal rate of
      cGMP synthesis at low [Ca(2+)] dropped 2-fold and (b) the half-maximal rate of
      cGMP synthesis was attained at a higher than normal [Ca(2+)]. The addition of an
      antibody raised against mouse GCAP2 produced similar effects on the guanylyl
      cyclase activity in wild type retinas. Flash responses of GCAP2 knock-out rods
      recovered more slowly than normal. Knock-out rods became more sensitive to
      flashes and to steps of illumination but tended to saturate at lower intensities,
      as compared with wild type rods. Therefore, GCAP2 regulation of guanylyl cyclase
      activity quickens the recovery of flash and step responses and adjusts the
      operating range of rods to higher intensities of ambient illumination.

PMID- 18723511
TI  - Avian sarcoma virus and human immunodeficiency virus, type 1 use different
      subsets of ESCRT proteins to facilitate the budding process.
AB  - Members of the Nedd4 family of E3 ubiquitin ligases bind the L domain in avian
      sarcoma virus (ASV) Gag and facilitate viral particle release. Translational
      fusion of ASV Gag with an L domain deletion (Deltap2b) to proteins that comprise
      ESCRT-I, -II, and -III (the endocytic sorting complexes required for transport)
      rescued both Gag ubiquitination and particle release from cells. The ESCRT-I
      factors Vps37C or Tsg101 were more effective in rescue of Gag/Deltap2b budding
      than the ESCRT-II factor Eap20 or the ESCRT-III component CHMP6. Thus ESCRT
      components can substitute for Nedd4 family members in ASV Gag release. Unlike
      wild type, ASV Gag/Deltap2b -ESCRT chimeras failed to co-immunoprecipitate with
      co-expressed hemagglutinin-tagged Nedd4, indicating that Nedd4 was not stably
      associated with these Gag fusions. Release of the Gag-ESCRT-I or -II fusions was
      inhibited by a dominant negative mutant of Vps4 ATPase similar to wild type ASV
      Gag. In contrast to ASV Gag, HIV-1 Gag containing an L domain inactivating
      mutation (P7L) was efficiently rescued by fusion to a component of ESCRT-III
      (Chmp6) but not ESCRT-II (Eap20). Depletion of the endogenous pool of Eap20
      (ESCRT-II) had little effect on HIV-1 Gag release but blocked ASV Gag release. In
      contrast, depletion of the endogenous pool of Vps37C (ESCRT-I) had little effect
      on ASV but blocked HIV-1 Gag release. Furthermore, an N-terminal fragment of
      Chmp6 inhibited both HIV-1 and ASV Gag release in a dominant negative manner.
      Taken together, these results indicate that ASV and HIV-1 Gag utilize different
      combinations of ESCRT proteins to facilitate the budding process, although they
      share some common elements.

PMID- 18723512
TI  - Hepatitis C viral NS3-4A protease activity is enhanced by the NS3 helicase.
AB  - Non-structural protein 3 (NS3) is a multifunctional enzyme possessing serine
      protease, NTPase, and RNA unwinding activities that are required for hepatitis C
      viral (HCV) replication. HCV non-structural protein 4A (NS4A) binds to the N
      terminal NS3 protease domain to stimulate NS3 serine protease activity. In
      addition, the NS3 protease domain enhances the RNA binding, ATPase, and RNA
      unwinding activities of the C-terminal NS3 helicase domain (NS3hel). To determine
      whether NS3hel enhances the NS3 serine protease activity, we purified truncated
      and full-length NS3-4A complexes and examined their serine protease activities
      under a variety of salt and pH conditions. Our results indicate that the helicase
      domain enhances serine protease activity, just as the protease domain enhances
      helicase activity. Thus, the two enzymatic domains of NS3-4A are highly
      interdependent. This is the first time that such a complete interdependence has
      been demonstrated for a multifunctional, single chain enzyme. NS3-4A domain
      interdependence has important implications for function during the viral
      lifecycle as well as for the design of inhibitor screens that target the NS3-4A
      protease.

PMID- 18723513
TI  - Regulation of postsynaptic RapGAP SPAR by Polo-like kinase 2 and the SCFbeta-TRCP
      ubiquitin ligase in hippocampal neurons.
AB  - The ubiquitin-proteasome pathway (UPP) regulates synaptic function, but little is
      known about specific UPP targets and mechanisms in mammalian synapses. We report
      here that the SCF(beta-TRCP) complex, a multisubunit E3 ubiquitin ligase, targets
      the postsynaptic spine-associated Rap GTPase activating protein (SPAR) for
      degradation in neurons. SPAR degradation by SCF(beta-TRCP) depended on the
      activity-inducible protein kinase Polo-like kinase 2 (Plk2). In the presence of
      Plk2, SPAR physically associated with the SCF(beta-TRCP) complex through a
      canonical phosphodegron. In hippocampal neurons, disruption of the SCF(beta-TRCP)
      complex by overexpression of dominant interfering beta-TRCP or Cul1 constructs
      prevented Plk2-dependent degradation of SPAR. Our results identify a specific E3
      ubiquitin ligase that mediates degradation of a key postsynaptic regulator of
      synaptic morphology and function.

PMID- 18723514
TI  - Beta-catenin levels influence rapid mechanical responses in osteoblasts.
AB  - Mechanical loading of bone initiates an anabolic, anticatabolic pattern of
      response, yet the molecular events involved in mechanical signal transduction are
      not well understood. Wnt/beta-catenin signaling has been recognized in promoting
      bone anabolism, and application of strain has been shown to induce beta-catenin
      activation. In this work, we have used a preosteoblastic cell line to study the
      effects of dynamic mechanical strain on beta-catenin signaling. We found that
      mechanical strain caused a rapid, transient accumulation of active beta-catenin
      in the cytoplasm and its translocation to the nucleus. This was followed by up
      regulation of the Wnt/beta-catenin target genes Wisp1 and Cox2, with peak
      responses at 4 and 1 h of strain, respectively. The increase of beta-catenin was
      temporally related to the activation of Akt and subsequent inactivation of
      GSK3beta, and caveolin-1 was not required for these molecular events. Application
      of Dkk-1, which disrupts canonical Wnt/LRP5 signaling, did not block strain
      induced nuclear translocation of beta-catenin or up-regulation of Wisp1 and Cox2
      expression. Conditions that increased basal beta-catenin levels, such as lithium
      chloride treatment or repression of caveolin-1 expression, were shown to enhance
      the effects of strain. In summary, mechanical strain activates Akt and
      inactivates GSK3beta to allow beta-catenin translocation, and Wnt signaling
      through LRP5 is not required for these strain-mediated responses. Thus, beta
      catenin serves as both a modulator and effector of mechanical signals in bone
      cells.

PMID- 18723515
TI  - A novel mechanism of G protein-coupled receptor functional selectivity.
      Muscarinic partial agonist McN-A-343 as a bitopic orthosteric/allosteric ligand.
AB  - Many G protein-coupled receptors (GPCRs) possess allosteric binding sites
      distinct from the orthosteric site utilized by their cognate ligands, but most
      GPCR allosteric modulators reported to date lack signaling efficacy in their own
      right. McN-A-343 (4-(N-(3-chlorophenyl)carbamoyloxy)-2-butynyltrimethylammonium
      chloride) is a functionally selective muscarinic acetylcholine receptor (mAChR)
      partial agonist that can also interact allosterically at the M(2) mAChR. We
      hypothesized that this molecule simultaneously utilizes both an allosteric and
      the orthosteric site on the M(2) mAChR to mediate these effects. By synthesizing
      progressively truncated McN-A-343 derivatives, we identified two, which minimally
      contain 3-chlorophenylcarbamate, as pure allosteric modulators. These compounds
      were positive modulators of the orthosteric antagonist N-[(3)H]methylscopolamine,
      but in functional assays of M(2) mAChR-mediated ERK1/2 phosphorylation and
      guanosine 5'-3-O-([(35)S]thio)triphosphate binding, they were negative modulators
      of agonist efficacy. This negative allosteric effect was diminished upon mutation
      of Y177A in the second extracellular (E2) loop of the M(2) mAChR that is known to
      reduce prototypical allosteric modulator potency. Our results are consistent with
      McN-A-343 being a bitopic orthosteric/allosteric ligand with the allosteric
      moiety engendering partial agonism and functional selectivity. This finding
      suggests a novel and largely unappreciated mechanism of "directed efficacy"
      whereby functional selectivity may be engendered in a GPCR by utilizing an
      allosteric ligand to direct the signaling of an orthosteric ligand encoded within
      the same molecule.

PMID- 18723516
TI  - Three-dimensional reconstruction of human cystic fibrosis transmembrane
      conductance regulator chloride channel revealed an ellipsoidal structure with
      orifices beneath the putative transmembrane domain.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel
      is a membrane-integral protein that belongs to an ATP-binding cassette
      superfamily. Mutations in the CFTR gene cause cystic fibrosis in which salt,
      water, and protein transports are defective in various tissues. Here we expressed
      wild-type human CFTR as a FLAG-fused protein in HEK293 cells heterologously and
      purified it in three steps: anti-FLAG and wheat germ agglutinin affinity
      chromatographies and size exclusion chromatography. The stoichiometry of the
      protein was analyzed using various biochemical approaches, including chemical
      cross-linking, blue-native PAGE, size exclusion chromatography, and electron
      microscopy (EM) observation of antibody-decorated CFTR. All these data support a
      dimeric assembly of CFTR. Using 5,039 automatically selected particles from
      negatively stained EM images, the three-dimensional structure of CFTR was
      reconstructed at 2-nm resolution assuming a 2-fold symmetry. CFTR, presumably in
      a closed state, was shown to be an ellipsoidal particle with dimensions of 120 x
      106 x 162 A. It comprises a small dome-shaped extracellular and membrane-spanning
      domain and a large cytoplasmic domain with orifices beneath the putative
      transmembrane domain. EM observation of CFTR.anti-regulatory domain antibody
      complex confirmed that two regulatory domains are located around the bottom end
      of the larger oval cytoplasmic domain.

PMID- 18723517
TI  - Development and validation of a preoperative scoring system to predict 30 day
      mortality in patients undergoing hip fracture surgery.
AB  - BACKGROUND: Hip fractures are common in the elderly and have a high 30 day
      postoperative mortality. The ability to recognize patients at high risk of poor
      outcomes before operation would be an important clinical advance. This study has
      determined key prognostic factors predicting 30 day mortality in a hip fracture
      population, and incorporated them into a scoring system to be used on admission.
      METHODS: A cohort study was conducted at the Queen's Medical Centre, Nottingham,
      over a period of 7 yr. Complete data were collected from 4967 patients and
      analysed. Forward univariate logistic regression was used to select the
      independent predictor variables of 30 day mortality, and then multivariate
      logistic regression was applied to the data to construct and validate the scoring
      system. RESULTS: The variables found to be independent predictors of mortality at
      30 days were: age (66-85 yr, > or =86 yr), sex (male), number of co-morbidities
      (> or =2), mini-mental test score (< or =6 out of 10), admission haemoglobin
      concentration (< or =10 g dl(-1)), living in an institution, and presence of
      malignant disease. These variables were subsequently incorporated into a risk
      score, the Nottingham Hip Fracture Score. The number of deaths observed at 30
      days, and the number of deaths predicted by the scoring system, indicated good
      concordance (chi(2) test, P=0.79). The area (SE) under the receiver operating
      characteristic curve was 0.719 (0.018), which demonstrated a reasonable
      predictive value for the score. CONCLUSIONS: We have developed and validated a
      scoring system that reliably predicts the probability of mortality at 30 days for
      patients after hip fracture.

PMID- 18723518
TI  - BSR DMARD monitoring guidelines: sulfasalazine.

PMID- 18723519
TI  - Rate-responsive pacing in patients with heart failure: long-term results of a
      randomized study.
AB  - AIMS: Chronotropic incompetence (CI) in patients with congestive heart failure
      (CHF) develops frequently under beta-blocker and amiodarone therapy. It can be
      corrected by pacing. We performed a randomized study to test whether pacing is
      beneficial in CHF patients with CI. METHODS AND RESULTS: Congestive heart failure
      patients under combined beta-blocker and amiodarone therapy (n = 77) were
      randomly assigned to inhibited pacing (INH; basal rate 40 bpm/hysteresis 30 bpm;
      n = 38) or to DDDR pacing with optimized atrioventricular delay (OPT; stimulation
      rate 65-120 bpm, n = 39). Groups showed similar baseline values in NYHA class,
      heart rate, and ejection fraction (EF) and were followed up to 10 years. The
      resting and mean 24 h heart rate after 1 year decreased by -2.6/-5 bpm in INH,
      but increased by +3.6/+6.0 bpm in the OPT group (P < 0.001). The QRS interval
      after 1 year increased by 12 +/- 23 ms in the INH group, but +32 +/- 36 ms in the
      OPT group (P < 0.01). Patients with INH developed a greater left ventricular EF
      (LVEF) when compared with OPT patients (+10.6 +/- 8 vs. +2 +/- 10%, respectively;
      P = 0.04). Changes in LVEF were negatively correlated with heart rate, but not
      with QRS width changes. Prognosis and the event rate were better in the INH
      group. CONCLUSION: In the long-term follow-up, single-site ventricular pacing in
      patients with CHF and low LVEF is associated with significant clinical events and
      a poor prognosis.

PMID- 18723520
TI  - Improving position-specific predictions of protein functional sites using
      phylogenetic motifs.
AB  - MOTIVATION: Accurate computational prediction of protein functional sites is
      critical to maximizing the utility of recent high-throughput sequencing efforts.
      Among the available approaches, position-specific conservation scores remain
      among the most popular due to their accuracy and ease of computation.
      Unfortunately, high false positive rates remain a limiting factor. Using
      phylogenetic motifs (PMs), we have developed two combined (conservation + PMs)
      prediction schemes that significantly improve prediction accuracy. RESULTS: Our
      first approach, called position-specific MINER (psMINER), rank orders alignment
      columns by conservation. Subsequently, positions that are also not identified as
      PMs are excluded from the prediction set. This approach improves prediction
      accuracy, in a statistically significant way, compared to the underlying
      conservation scores. Increased accuracy is a general result, meaning improvement
      is observed over several different conservation scores that span a continuum of
      complexity. In addition, a hybrid MINER (hMINER) that quantitatively considers
      both scoring regimes provides further improvement. More importantly, it provides
      critical insight into the relative importance of phylogeny versus alignment
      conservation. Both methods outperform other common prediction algorithms that
      also utilize phylogenetic concepts. Finally, we demonstrate that the presented
      results are critically sensitive to functional site definition, thus highlighting
      the need for more complete benchmarks within the prediction community.

PMID- 18723521
TI  - ProfDistS: (profile-) distance based phylogeny on sequence--structure alignments.
AB  - MOTIVATION: The Profile Neighbor Joining (PNJ) algorithm as implemented in the
      software ProfDist is computationally efficient in reconstructing very large
      trees. Besides the huge amount of sequence data the structure is important in RNA
      alignment analysis and phylogenetic reconstruction. RESULTS: For this ProfDistS
      provides a phylogenetic workflow that uses individual RNA secondary structures in
      reconstructing phylogenies based on sequence-structure alignments-using PNJ with
      manual or iterative and automatic profile definition. Moreover, ProfDistS can
      deal also with protein sequences.

PMID- 18723522
TI  - AMIN domains have a predicted role in localization of diverse periplasmic protein
      complexes.
AB  - We describe AMIN (Amidase N-terminal domain), a novel protein domain found
      specifically in bacterial periplasmic proteins. AMIN domains are widely
      distributed among peptidoglycan hydrolases and transporter protein families.
      Based on experimental data, contextual information and phyletic profiles, we
      suggest that AMIN domains mediate the targeting of periplasmic or extracellular
      proteins to specific regions of the bacterial envelope.

PMID- 18723523
TI  - Optimal design of thermally stable proteins.
AB  - MOTIVATION: For many biotechnological purposes, it is desirable to redesign
      proteins to be more structurally and functionally stable at higher temperatures.
      For example, chemical reactions are intrinsically faster at higher temperatures,
      so using enzymes that are stable at higher temperatures would lead to more
      efficient industrial processes. We describe an innovative and computationally
      efficient method called Improved Configurational Entropy (ICE), which can be used
      to redesign a protein to be more thermally stable (i.e. stable at high
      temperatures). This can be accomplished by systematically modifying the amino
      acid sequence via local structural entropy (LSE) minimization. The minimization
      problem is modeled as a shortest path problem in an acyclic graph with
      nonnegative weights and is solved efficiently using Dijkstra's method.

PMID- 18723525
TI  - Novel expression and transcriptional regulation of FoxJ1 during oro-facial
      morphogenesis.
AB  - Axenfeld-Rieger syndrome (ARS) patients with PITX2 point mutations exhibit a wide
      range of clinical features including mild craniofacial dysmorphism and dental
      anomalies. Identifying new PITX2 targets and transcriptional mechanisms are
      important to understand the molecular basis of these anomalies. Chromatin
      immunoprecipitation assays demonstrate PITX2 binding to the FoxJ1 promoter and
      PITX2C transgenic mouse fibroblasts and PITX2-transfected cells have increased
      endogenous FoxJ1 expression. FoxJ1 is expressed at embryonic day 14.5 (E14.5) in
      early tooth germs, then down-regulated from E15.5-E17.5 and re-expressed in the
      inner enamel epithelium, oral epithelium, tongue epithelium, sub-mandibular
      salivary gland and hair follicles during E18.5 and neonate day 1. FoxJ1 and Pitx2
      exhibit overlapping expression patterns in the dental and oral epithelium. PITX2
      activates the FoxJ1 promoter and, Lef-1 and beta-catenin interact with PITX2 to
      synergistically regulate the FoxJ1 promoter. FoxJ1 physically interacts with the
      PITX2 homeodomain to synergistically regulate FoxJ1, providing a positive
      feedback mechanism for FoxJ1 expression. Furthermore, FoxJ1, PITX2, Lef-1 and
      beta-catenin act in concert to activate the FoxJ1 promoter. The PITX2 T68P ARS
      mutant protein physically interacts with FoxJ1; however, it cannot activate the
      FoxJ1 promoter. These data indicate a mechanism for the activity of the ARS
      mutant proteins in specific cell types and provides a basis for craniofacial/
      tooth anomalies observed in these patients. These data reveal novel
      transcriptional mechanisms of FoxJ1 and demonstrate a new role of FoxJ1 in oro
      facial morphogenesis.

PMID- 18723526
TI  - Tuberculotic osteomyelitis of rib--a surgical entity.
AB  - Primary tuberculotic osteomyelitis (TBOM) of the rib is rare. We report our
      experience of seven patients presenting with primary TBOM of rib. Over a period
      of eight years, otherwise healthy patients presenting with discharging sinus on
      the chest wall were managed. Patients included four males and three females, aged
      between 4 and 18 years. Following history and examination, radiological and
      histological investigations were performed. After confirming osteomyelitis of
      rib, excision of the sinus tract along with subperiosteal resection of the
      affected part of the rib was done. Tuberculosis was confirmed on histological
      examination of the resected specimens. Oral anti-tubercular therapy (ATT) was
      given for a period of one year. Patients were followed for 5-8 years. The lesion
      was demonstrable in all the patients on plain X-ray. Histological confirmation of
      tuberculosis (TB) before surgery could be done in one patient. The anterio
      lateral part of the rib was most commonly affected. Mean operative time was 35
      min. Mean postoperative hospital stay was four days. There were no wound
      complications. No recurrence or relapse was seen. Resection of affected part of
      the rib with the sinus tract followed by oral ATT for one year is an effective
      modality of treatment for TBOM of rib.

PMID- 18723524
TI  - Common variation in the miR-659 binding-site of GRN is a major risk factor for
      TDP43-positive frontotemporal dementia.
AB  - Loss-of-function mutations in progranulin (GRN) cause ubiquitin- and TAR DNA
      binding protein 43 (TDP-43)-positive frontotemporal dementia (FTLD-U), a
      progressive neurodegenerative disease affecting approximately 10% of early-onset
      dementia patients. Here we expand the role of GRN in FTLD-U and demonstrate that
      a common genetic variant (rs5848), located in the 3'-untranslated region (UTR) of
      GRN in a binding-site for miR-659, is a major susceptibility factor for FTLD-U.
      In a series of pathologically confirmed FTLD-U patients without GRN mutations, we
      show that carriers homozygous for the T-allele of rs5848 have a 3.2-fold
      increased risk to develop FTLD-U compared with homozygous C-allele carriers (95%
      CI: 1.50-6.73). We further demonstrate that miR-659 can regulate GRN expression
      in vitro, with miR-659 binding more efficiently to the high risk T-allele of
      rs5848 resulting in augmented translational inhibition of GRN. A significant
      reduction in GRN protein was observed in homozygous T-allele carriers in vivo,
      through biochemical and immunohistochemical methods, mimicking the effect of
      heterozygous loss-of-function GRN mutations. In support of these findings, the
      neuropathology of homozygous rs5848 T-allele carriers frequently resembled the
      pathological FTLD-U subtype of GRN mutation carriers. We suggest that the
      expression of GRN is regulated by miRNAs and that common genetic variability in a
      miRNA binding-site can significantly increase the risk for FTLD-U. Translational
      regulation by miRNAs may represent a common mechanism underlying complex
      neurodegenerative disorders.

PMID- 18723528
TI  - What ever happened to the Mediterranean diet?

PMID- 18723529
TI  - Hydrogen sulfide and oxygen sensing: implications in cardiorespiratory control.
AB  - Although all cells are variously affected by oxygen, a few have the
      responsibility of monitoring oxygen tensions and initiating key homeostatic
      responses when P(O2) falls to critical levels. These ;oxygen-sensing' cells
      include the chemoreceptors in the gills (neuroepithelial cells), airways
      (neuroepithelial bodies) and vasculature (carotid bodies) that initiate
      cardiorespiratory reflexes, oxygen sensitive chromaffin cells associated with
      systemic veins or adrenal glands that regulate the rate of catecholamine
      secretion, and vascular smooth muscle cells capable of increasing blood flow to
      systemic tissues, or decreasing it through the lungs. In spite of intense
      research, and enormous clinical applicability, there is little, if any, consensus
      regarding the mechanism of how these cells sense oxygen and transduce this into
      the appropriate physiological response. We have recently proposed that the
      metabolism of hydrogen sulfide (H2S) may serve as an 'oxygen sensor' in
      vertebrate vascular smooth muscle and preliminary evidence suggests it has
      similar activity in gill chemoreceptors. In this proposed mechanism, the cellular
      concentration of H2S is determined by the simple balance between constitutive H2S
      production in the cytoplasm and H2S oxidation in the mitochondria; when tissue
      oxygen levels fall the rate of H2S oxidation decreases and the concentration of
      biologically active H2S in the tissue increases. This commentary briefly
      describes the oxygen-sensitive tissues in fish and mammals, delineates the
      current hypotheses of oxygen sensing by these tissues, and then critically
      evaluates the evidence for H2S metabolism in oxygen sensing.

PMID- 18723530
TI  - The movements of limb segments and joints during locomotion in African and Asian
      elephants.
AB  - As the largest extant terrestrial animals, elephants do not trot or gallop but
      can move smoothly to faster speeds without markedly changing their kinematics,
      yet with a shift from vaulting to bouncing kinetics. To understand this unusual
      mechanism, we quantified the forelimb and hindlimb motions of eight Asian
      elephants (Elephas maximus) and seven African elephants (Loxodonta africana). We
      used 240 Hz motion analysis (tracking 10 joint markers) to measure the
      flexion/extension angles and angular velocities of the limb segments and joints
      for 288 strides across an eightfold range of speeds (0.6-4.9 m s(-1)) and a
      sevenfold range of body mass (521-3684 kg). We show that the columnar limb
      orientation that elephants supposedly exemplify is an oversimplification--few
      segments or joints are extremely vertical during weight support (especially at
      faster speeds), and joint flexion during the swing phase is considerable. The
      'inflexible' ankle is shown to have potentially spring-like motion, unlike the
      highly flexible wrist, which ironically is more static during support. Elephants
      use approximately 31-77% of their maximal joint ranges of motion during rapid
      locomotion, with this fraction increasing distally in the limbs, a trend observed
      in some other running animals. All angular velocities decrease with increasing
      size, whereas smaller elephant limbs are not markedly more flexed than adults. We
      find no major quantitative differences between African and Asian elephant
      locomotion but show that elephant limb motions are more similar to those of
      smaller animals, including humans and horses, than commonly recognized. Such
      similarities have been obscured by the reliance on the term ;columnar' to
      differentiate elephant limb posture from that of other animals. Our database will
      be helpful for identifying elephants with unusual limb movements, facilitating
      early recognition of musculoskeletal pathology.

PMID- 18723531
TI  - Multifocal optical systems and pupil dynamics in birds.
AB  - In animal eyes of the camera type longitudinal chromatic aberration causes
      defocus that is particularly severe in species with short depth of focus. In a
      variety of vertebrates, multifocal optical systems compensate for longitudinal
      chromatic aberration by concentric zones of different refractive powers. Since a
      constricting circular pupil blocks peripheral zones, eyes with multifocal optical
      systems often have slit pupils that allow light to pass through all zones,
      irrespective of the state of pupil constriction. Birds have circular pupils and
      were therefore assumed to have monofocal optical systems. We examined the eyes of
      45 species (12 orders) of bird using videorefractometry, and the results are
      surprising: 29 species (10 orders) have multifocal systems, and only five species
      (five orders) have monofocal systems. The results from 11 species (four orders)
      are inconclusive. We propose that pupils 'switching' between being fully opened
      (multifocal principle) to maximally closed (pinhole principle) can make
      multifocal optical systems useful for animals with circular pupils. Previous
      results indicate that mice have both multifocal optical systems and switching
      pupils. Our results suggest that parrots may use a similar mechanism. By
      contrast, owl pupils responded weakly to changes in illumination and stayed
      remarkably wide even in full daylight. Moreover, the parrots opened their pupils
      at higher light levels than owls, which correlates with the differences in
      sensitivity between diurnal and nocturnal eyes.

PMID- 18723532
TI  - Allometry of evaporative water loss in marsupials: implications of the effect of
      ambient relative humidity on the physiology of brushtail possums (Trichosurus
      vulpecula).
AB  - To better understand the effects of ambient relative humidity (RH) on
      physiological variables and the implications of RH-correcting evaporative water
      loss (EWL) data for marsupials, we examined the effect of RH on EWL, body
      temperature (Tb), metabolic rate (MR) and thermal conductance (C) of the
      brushtail possum (Trichosurus vulpecula), a medium-sized marsupial. Correcting
      EWL data for 27 species of marsupial for water vapour pressure deficit (DeltaWVP)
      in the chamber during measurement significantly increased, rather than decreased,
      the variability of the allometric relationship for EWL. For the brushtail possum,
      both ambient temperature (Ta) and RH significantly affected EWL. At Ta=25 degrees
      C, EWL was independent of RH at "63% RH, but decreased linearly at higher RH
      values. At Ta=30 degrees C, EWL was significantly related to RH from 26% to 92%
      RH. There was a significant effect of Ta on Tb and dry thermal conductance (Cdry;
      higher at 30 degrees C), but no effect of RH. For MR and wet thermal conductance
      (Cwet) there was a significant effect of Ta (MR higher and Cwet lower at 25
      degrees C), and RH at Ta=30 degrees C (MR higher and Cwet lower at the lowest RH)
      but not at 25 degrees C. Our results indicate that brushtail possums do not
      necessarily show the linear relationship between ambient RH and EWL expected for
      an endotherm, possibly because of behavioural modification of their immediate
      microclimate. This may account for the failure of WVP deficit correction to
      improve the allometric EWL relationship for marsupials. Chamber RH is an
      important environmental factor to be considered when measuring standard
      physiological variables such as MR and Cwet.

PMID- 18723533
TI  - The effects of gravity on human walking: a new test of the dynamic similarity
      hypothesis using a predictive model.
AB  - The dynamic similarity hypothesis (DSH) suggests that differences in animal
      locomotor biomechanics are due mostly to differences in size. According to the
      DSH, when the ratios of inertial to gravitational forces are equal between two
      animals that differ in size [e.g. at equal Froude numbers, where Froude =
      velocity2/(gravity x hip height)], their movements can be made similar by
      multiplying all time durations by one constant, all forces by a second constant
      and all linear distances by a third constant. The DSH has been generally
      supported by numerous comparative studies showing that as inertial forces differ
      (i.e. differences in the centripetal force acting on the animal due to variation
      in hip heights), animals walk with dynamic similarity. However, humans walking in
      simulated reduced gravity do not walk with dynamically similar kinematics. The
      simulated gravity experiments did not completely account for the effects of
      gravity on all body segments, and the importance of gravity in the DSH requires
      further examination. This study uses a kinematic model to predict the effects of
      gravity on human locomotion, taking into account both the effects of
      gravitational forces on the upper body and on the limbs. Results show that
      dynamic similarity is maintained in altered gravitational environments. Thus, the
      DSH does account for differences in the inertial forces governing locomotion
      (e.g. differences in hip height) as well as differences in the gravitational
      forces governing locomotion.

PMID- 18723534
TI  - Methyl farnesoate couples environmental changes to testicular development in the
      crab Carcinus maenas.
AB  - Carcinus maenas males have two major color phases. Green-phase males molt
      frequently and tend to live in brackish estuaries during the summer. After
      becoming red-phase males, they molt infrequently, have higher mating success, and
      live in cooler, deeper water. We found profound differences between these two
      phases in the way salinity and temperature affect hemolymph levels of methyl
      farnesoate (MF), a hormone that affects crustacean reproduction. Few green-phase
      males (<10%) had detectable MF in 33 ppt seawater (SW) at 11 or 18 degrees C. By
      contrast, about 30% of the red-phase males had detectable MF at either
      temperature. After transfer to 5 ppt SW, none of the green-phase males had
      detectable MF at 11 degrees C whereas 100% of green-phase males did at 18 degrees
      C. By contrast, 100% of the red-phase males had detectable MF in 5 ppt SW at
      either temperature. At 11 degrees C, green-phase males had detectable MF after
      eyestalk ablation (ESA), showing that they can produce MF. There was no
      additional increase in MF levels when ESA animals of either color phase were
      transferred to 5 ppt SW, suggesting that the eyestalk is the primary regulator of
      the MF response to low salinity. MF levels of green-phase males were increased by
      injecting MF, by ESA, or by exposure to 5 ppt SW at 18 degrees C. The testicular
      index of these treated animals nearly doubled after two weeks. Our results
      strongly suggest that environmental conditions such as temperature and salinity,
      affect testicular development in this crab by changing its MF levels.

PMID- 18723535
TI  - Predicting acoustic orientation in complex real-world environments.
AB  - Animals have to accomplish several tasks in their lifetime, such as finding food
      and mates and avoiding predators. Animals that locate these using sound need to
      detect, recognize and localize appropriate acoustic objects in their environment,
      typically in noisy, non-ideal conditions. Quantitative models attempting to
      explain or predict animal behaviour should be able to accurately simulate
      behaviour in such complex, real-world conditions. Female crickets locate
      potential mates in choruses of simultaneously calling males. In the present
      study, we have tested field cricket acoustic orientation behaviour in complex
      acoustic conditions in the field and also successfully predicted female
      orientation and paths under these conditions using a simulation model based on
      auditory physiology. Such simulation models can provide powerful tools to predict
      and dissect patterns of behaviour in complex, natural environments.

PMID- 18723536
TI  - Bile salts are effective taste stimuli in channel catfish.
AB  - Bile salts are known olfactory stimuli for teleosts, but only a single report has
      indicated that the taste system of a fish was sensitive to this class of stimuli.
      Here, gustatory responses of the channel catfish, Ictalurus punctatus, to four
      bile salts that included taurine-, glycine- and non-conjugated compounds along
      with three stimulatory amino acids as a comparison were investigated using
      extracellular electrophysiological techniques. Integrated multiunit responses
      were obtained from the branch of the facial nerve innervating taste buds on the
      maxillary barbel. Bile salts were shown to be highly effective facial taste
      stimuli, with estimated electrophysiological thresholds for three of the four
      tested bile salts of approximately 10(-11) mol l(-1) to 10(-10) mol l(-1),
      slightly lower by 1-2 log units than those to amino acids in the same species.
      Although the sensitivity of the facial taste system of the channel catfish to
      bile salts is high, the relative magnitude of the response to suprathreshold
      concentrations of bile salts was significantly less than that to amino acids.
      Multiunit cross-adaptation experiments indicate that bile salts and amino acids
      bind to relatively independent receptor sites; however, nerve-twig data and
      single-fiber recordings suggest that both independent and shared neural pathways
      exist for the transmission of bile salt and amino acid information to the primary
      gustatory nucleus of the medulla.

PMID- 18723537
TI  - The physiology of the midgut of Lutzomyia longipalpis (Lutz and Neiva 1912): pH
      in different physiological conditions and mechanisms involved in its control.
AB  - Nutrient digestion and absorption after blood feeding are important events for
      Lutzomyia longipalpis, which uses these nutrients to produce eggs. In this
      context, the pH inside the digestive tract is an important physiological feature
      as it can markedly influence the digestive process as well as interfere with
      Leishmania development in infected phlebotomines. It was described previously
      that unfed females have an acidic midgut (pH 6). In this study, the pH inside the
      midgut of blood-fed females was measured. The abdominal midgut (AM) pH varied
      from 8.15+/-0.31 in the first 10 h post-blood meal to 7.7+/-0.17 after 24 h.
      While the AM was alkaline during blood digestion, the pH in the thoracic midgut
      (TM) remained acidic (5.5-6.0). In agreement with these findings, the enzyme
      alpha-glucosidase, which has an optimum pH of 5.8, is mainly encountered in the
      acidic TM. The capacity of unfed females to maintain the acidic intestinal pH was
      also evaluated. Our results showed the presence of an efficient mechanism that
      maintains the pH almost constant at about 6 in the midgut, but not in the crop.
      This mechanism is promptly interrupted in the AM by blood ingestion. RT-PCR
      results indicated the presence of carbonic anhydrase in the midgut cells, which
      apparently is required to maintain the pH at 6 in the midgut of unfed females.
      Investigations on the phenomenon of alkalization observed after blood ingestion
      indicated that two mechanisms are involved: in addition to the alkalization
      promoted by CO2 volatilization there is a minor contribution from a second
      mechanism not yet characterized. Some inferences concerning Leishmania
      development and pH in the digestive tube are presented.

PMID- 18723538
TI  - Cues for acoustic detection of prey: insect rustling sounds and the influence of
      walking substrate.
AB  - When insects walk, they generally produce sounds. These can reveal the walkers'
      presence and location to potential predators such as owls, bats and nocturnal
      primates. Additionally, predators might extract information on taxon,
      palatability, size or profitability from the rustling sounds. In contrast to ear
      morphology, hearing physiology and psychoacoustics of acoustically oriented
      predators, little attention has hitherto been paid to the acoustic structure and
      information content of prey sounds. An important element in the ecology of
      acoustic prey detection remained virtually unexplored: the influence of the
      substrate type on rustling sounds. In this study, we analysed amplitude and
      frequency parameters from insects walking on various natural substrates, in both
      Germany (Carabus beetles) and Madagascar (various beetles and cockroaches). The
      data show that rustling sound amplitude and frequency content depend on substrate
      type. On moist substrates arthropods produced less intense and less broadband
      rustling sounds than on dry substrates. Sound pressure level was reduced by about
      6 dB, halving the detection range for the predator. For a given insect, rustling
      sound amplitude increased with walking speed. Finally, we found that the
      previously established correlation of arthropod size and rustling amplitude holds
      across multiple substrates. Based on these data, we provide for the first time
      estimates of realistic detection distances in the field. These distances range
      from below 1 m to over 13 m, depending on the substrate, insect mass, walking
      speed and background noise level. These estimates are crucial for an
      understanding of the foraging ecology, foraging efficiency and sensory ecology of
      acoustic predators.

PMID- 18723539
TI  - Comparing memory-forming capabilities between laboratory-reared and wild Lymnaea:
      learning in the wild, a heritable component of snail memory.
AB  - We set out to determine whether the ability to form long-term memory (LTM) is
      influenced by laboratory rearing. We investigated the ability of four populations
      of Lymnaea stagnalis to form LTM following operant conditioning both in the
      freely behaving animal and at the electrophysiological level in a neuron, RPeD1,
      which is a necessary site for LTM. We hypothesized that laboratory rearing
      results in a decreased ability to form LTM because rearing does not occur in an
      'enriched environment'. Of the four populations examined, two were collected in
      the wild and two were reared in the laboratory--specifically, (1) wild Dutch
      snails; (2) their laboratory-reared offspring; (3) wild Southern Alberta snails
      (Belly); and (4) their laboratory-reared offspring. We found that Belly snails
      had an enhanced capability of forming LTM compared with Dutch laboratory-reared
      snails. That is, the Belly snails, which are much darker in colour than
      laboratory-reared snails (i.e. blonds), were 'smarter'. However, when we tested
      the offspring of Belly snails reared in the laboratory we found that these snails
      still had the enhanced ability to form LTM, even though they were now just as
      'blond' as their laboratory-reared Dutch cousins. Finally, we collected wild
      Dutch snails, which are also dark, and found that their ability to form LTM was
      not different to that of their laboratory-reared offspring. Thus, our hypothesis
      was not proved. Rather, we now hypothesize that there are strain differences
      between the Belly and Dutch snails, irrespective of whether they are reared in
      the wild or in the laboratory.

PMID- 18723540
TI  - Exploration and navigation in the blind mole rat (Spalax ehrenbergi): global
      calibration as a primer of spatial representation.
AB  - The aim of this study was to uncover the process of initial spatial mapping of
      the environment. For this, blind mole rats (Spalax ehrenbergi), were tested in an
      unfamiliar square arena, in order to reveal how they construct a spatial
      representation. The mole rats first displayed a build-up phase, in which they
      gradually formed a path along the perimeter while travelling slowly, frequently
      pausing and repeating previously travelled segments of the path. This behaviour
      was followed by a free-travel phase, in which the mole rats appeared to locomote
      smoothly along the perimeter and through the centre of the arena while travelling
      faster with fewer stops or repetitions of path segments. Familiarity with the
      environment was reflected in local shortcuts at the arena corners and global
      shortcuts (crosscuts) through the arena centre. We suggest that scanning the
      perimeter throughout the build-up phase constitute a process of calibration, i.e.
      forming an initial representation of the size and perhaps the shape of the
      environment--a sort of basic global map. We further suggest that this calibration
      is later used for navigation, as indicated by the emergence of global crosscuts
      in the subsequent phase. Further investigation of the build-up phase, e.g. by
      manipulating environment size, might provide additional insight into the course
      of establishment of global environment representation (mapping).

PMID- 18723541
TI  - Chemical and mechanical bioerosion of boring sponges from Mexican Pacific coral
      reefs.
AB  - Species richness (S) and frequency of invasion (IF) by boring sponges on living
      colonies of Pocillopora spp. from National Park Isla Isabel (Mexico, East Pacific
      Ocean) are presented. Twelve species belonging to the genera Aka, Cliona, Pione,
      Thoosa and Spheciospongia were found, and 56% of coral colonies were invaded by
      boring sponges, with Cliona vermifera Hancock 1867 being the most abundant
      species (30%). Carbonate dissolution rate and sediment production were quantified
      for C. vermifera and Cliona flavifodina Rutzler 1974. Both species exhibited
      similar rates of calcium carbonate (CaCO3) dissolution (1.2+/-0.4 and 0.5+/-0.2
      kg CaCO3 m(-2) year(-1), respectively, mean +/- s.e.m.), and sediment production
      (3.3+/-0.6 and 4.6+/-0.5 kg CaCO3 m(-2) year(-1)), resulting in mean bioerosion
      rates of 4.5+/-0.9 and 5.1+/-0.5 kg CaCO3 m(-2) year(-1), respectively. These
      bioerosion rates are close to previous records of coral calcification per unit of
      area, suggesting that sponge bioerosion alone can promote disequilibrium in the
      reef accretion/destruction ratio in localities that are heavily invaded by boring
      sponges. The proportion of dissolved material by C. vermifera and C. flavifodina
      (27 and 10.2%, respectively) confirms that chemical bioerosion plays an important
      role in sponge bioerosion and in the CaCO3 cycle in coral reefs.

PMID- 18723542
TI  - The scaling of safety factor in spider draglines.
AB  - This study documents the effect of body mass on the size and strength of
      draglines produced by the orb-weaving spider Araneus diadematus and the jumping
      spider Salticus scenicus. Silk samples obtained from individuals spanning the
      range from first-instar juveniles to gravid adults were tested to determine both
      the properties of the silk material and the strength and static safety factor of
      the draglines produced by each individual spider. Analysis of material properties
      indicates that the tensile strength and extensibility of the silks employed by
      each species are identical over the entire size range of the species. Analysis of
      the breaking forces for individual draglines, however, indicates that the
      draglines scale allometrically with the spider's body mass. For Araneus, breaking
      force (N) scales with body mass (kg) as Fmax=11.2M0.786, and the static safety
      factor (S(BW)=Fmax/Mg) scales as S(BW)=1.14M(-0.214). For Salticus,
      Fmax=0.363M0.66 and S(BW)=0.037M(-0.34). Thus, static safety factors decrease as
      these spiders grow, with values falling to 4-6 for adult Araneus and to 1-2 for
      adult Salticus. Analysis of these results suggests that the safety lines produced
      by these two species are not able to absorb the impact energy of most falls with
      a fixed length of pre-existing silk, except in the smallest of the Araneus
      spiders. It is therefore likely that both spiders must draw new silk from their
      spinnerets during falls to keep the dynamic loads on their safety-lines below
      failure levels.

PMID- 18723543
TI  - Reversed functional topology in the antennal lobe of the male European corn
      borer.
AB  - The European corn borer Ostrinia nubilalis (Hubner) is a model of evolution of
      sexual communication in insects. Two pheromone strains produce and respond to
      opposite ratios of the two pheromone components, Z11 and E11-tetradecenylacetate.
      The Z-strain uses a ratio of 97:3 of Z11:E11 tetradecenylacetate, whereas the E
      strain uses a ratio of 1:99. We studied how the difference in male preference
      correlates with differences in wiring of olfactory input and output neurons in
      the antennal lobe (AL). Activity-dependent anterograde staining, intracellular
      recording and immunocytochemistry were used to establish the structure and
      function of male olfactory receptor neurons (ORNs) and AL projection neurons
      (PNs). Physiologically characterized neurons were reconstructed using confocal
      microscopy of alpha-synapsin stained ALs. The ALs of males and females in both
      strains had approximately 64 glomeruli. In males the macroglomerular complex
      (MGC) was morphologically similar in the two strains and consisted of two major
      compartments, a large, medial compartment folded around a smaller, lateral one.
      Extensive physiological and morphological analysis revealed that in both strains
      the major pheromone component-specific ORNs and PNs arborize in the medial MGC
      glomerulus, whereas those sensitive to the minor pheromone component arborize in
      the lateral glomerulus. In other words, the two strains have an indistinguishable
      MGC morphology, but a reversed topology. Apparently, the single-gene-mediated
      shift that causes a radical change in behavior is located upstream of the
      antennal lobes, i.e. at the ORN level.

PMID- 18723544
TI  - Antennule morphology and flicking kinematics facilitate odor sampling by the
      spiny lobster, Panulirus argus.
AB  - Many arthropod olfactory appendages bear arrays of hair-like chemosensory
      sensillae. Odor molecules in the fluid around the animal must reach the surfaces
      of those hairs to be sensed. We used the lateral flagellum of the olfactory
      antennule of the spiny lobster, Panulirus argus, as a system to study how the
      morphology, orientation, and motion of sensilla-bearing appendages affects the
      small-scale water flow within the hair array. We tested whether antennule
      flicking enables lobsters to take discrete odor samples by measuring flow fields
      through an aesthetasc array on a dynamically scaled physical model of a P. argus
      antennule. Particle image velocimetry revealed that the magnitude and duration of
      velocity through the aesthetasc array during the rapid flick downstroke is just
      enough to allow complete replacement of the fluid entrained within the hair
      array. The complex zig-zag arrangement of aesthetascs hairs, combined with their
      offset orientation along the antennule, generates flow velocities that are
      uniform along the length of the hairs. This increases fluid exchange during the
      flick and reduces the boundary layer thickness surrounding the hairs. The return
      stroke occurs at about a quarter the speed of the flick, but the velocity of the
      fluid between the aesthetascs is approximately 25 times slower. The retained
      fluid during the return stroke remains virtually unstirred and sufficient time
      occurs for odor molecules to diffuse to aesthetasc surfaces.

PMID- 18723545
TI  - The effects of short-term antioxidant supplementation on oxidative stress and
      flight performance in adult budgerigars Melopsittacus undulatus.
AB  - Antioxidants are known to play an important role in quenching reactive oxygen
      species (ROS), thus ameliorating oxidative stress. Since increased metabolism
      associated with exercise can increase oxidative stress, dietary antioxidants may
      be a limiting factor in determining aspects of physical performance. Here we
      tested whether oxidative stress associated with flight exercise of captive adult
      budgerigars, Melopsittacus undulatus differed after they received a diet
      containing either enhanced (EQ) or reduced levels (RQ) of a nutritional
      supplement (Nutrivit) rich in antioxidants for 4 weeks. We also assessed
      differences in take-off escape time, a potential fitness-determining
      physiological capability. Oxidative stress was measured in two ways: comet assay
      to measure DNA damage; and analysis of malondialdehyde (MDA), a by-product of
      lipid peroxidation. Flight exercise appeared to increase oxidative stress.
      Moreover, birds had a higher percentage of intact DNA (fewer alkali labile sites)
      in one comet measure and lower levels of MDA after an EQ diet than after an RQ
      diet. We found no difference in flight performance between the two diets. Our
      results suggested that birds exerted maximum effort in escape flights, regardless
      of diet. However, this was at a cost of increased oxidative stress post-flight
      when on a reduced quality diet, but not when on an enhanced, antioxidant-rich
      diet. We suggest that dietary antioxidants may prove important in reducing
      exercise-related costs through multiple physiological pathways. Further work is
      necessary to fully understand the effects of antioxidants and oxidative stress on
      exercise performance in the longer term.

PMID- 18723546
TI  - Bioluminescent response of individual dinoflagellate cells to hydrodynamic stress
      measured with millisecond resolution in a microfluidic device.
AB  - Dinoflagellate bioluminescence serves as a model system for examining
      mechanosensing by suspended motile unicellular organisms. The response latency,
      i.e. the delay time between the mechanical stimulus and luminescent response,
      provides information about the mechanotransduction and signaling process, and
      must be accurately known for dinoflagellate bioluminescence to be used as a flow
      visualization tool. This study used a novel microfluidic device to measure the
      response latency of a large number of individual dinoflagellates with a
      resolution of a few milliseconds. Suspended cells of several dinoflagellate
      species approximately 35 microm in diameter were directed through a 200 microm
      deep channel to a barrier with a 15 microm clearance impassable to the cells.
      Bioluminescence was stimulated when cells encountered the barrier and experienced
      an abrupt increase in hydrodynamic drag, and was imaged using high numerical
      aperture optics and a high-speed low-light video system. The average response
      latency for Lingulodinium polyedrum strain HJ was 15 ms (N>300 cells) at the
      three highest flow rates tested, with a minimum latency of 12 ms. Cells produced
      multiple flashes with an interval as short as 5 ms between individual flashes,
      suggesting that repeat stimulation involved a subset of the entire intracellular
      signaling pathway. The mean response latency for the dinoflagellates Pyrodinium
      bahamense, Alexandrium monilatum and older and newer isolates of L. polyedrum
      ranged from 15 to 22 ms, similar to the latencies previously determined for
      larger dinoflagellates with different morphologies, possibly reflecting
      optimization of dinoflagellate bioluminescence as a rapid anti-predation
      behavior.

PMID- 18723547
TI  - Hydrozoan nematocytes send and receive synaptic signals induced by mechano
      chemical stimuli.
AB  - Nematocytes, the stinging cells of Hydrozoa, can be considered as prototypic
      mechanosensory hair cells bearing a concentric hair bundle, the cnidocil
      apparatus. These cells produce typical mechanoreceptor potentials in response to
      deflection of their cnidocil. Here we show that mechanosensory signals are
      relayed to neighbouring nematocytes via chemical neurotransmission and that
      nematocytes receive synaptic input from surrounding nematocytes, hair cells and
      probably from epithelial cells. Intracellular voltage recordings from stenotele
      nematocytes of capitate hydroid polyps showed two distinct types of responses
      when other nematocytes within the same tentacle were mechanically stimulated: (i)
      graded depolarizations of variable duration ('L-potentials'), and (ii) uniform
      impulse-like, often repetitive depolarizations ('T-potentials') that occurred in
      correlation with contractions of epitheliomuscular cells. Voltage clamp
      experiments showed that despite the stereotyped time course of T-potentials,
      their generation did not involve electrically excitable conductances. Instead,
      time course, post-stimulus delay, susceptibility to blockers of neurotransmission
      and gap junctions, and induction by electrical stimulation of other nematocytes
      indicate that L- and T-potentials are postsynaptic, most likely glutamatergic
      potentials. Both result from different presynaptic pathways: L-potentials are
      induced monosynaptically by presynaptic receptor potentials, T-potentials are
      most likely triggered by presynaptic action potentials propagating through the
      ectodermal epithelium via gap junctions. Moreover, contact-chemosensory
      (phospholipid) stimulation of the presynaptic nematocyte is a positive modulator
      of the nematocyte's afferent synaptic efficacy and of cnidocyst discharge, both
      triggered by mechanoreceptor potentials. The results reveal that hydrozoan
      nematocytes act as bimodal sensory cells, signalling coincident chemical and
      mechanical stimuli indicative of prey, and receive signals from other nematocytes
      and sensory cells.

PMID- 18723548
TI  - Metabolic and molecular stress responses of sublittoral bearded horse mussel
      Modiolus barbatus to warming sea water: implications for vertical zonation.
AB  - The present study set out to investigate the thermal limits of the Mediterranean
      bivalve Modiolus barbatus, acclimated to various temperatures, and includes a
      comparison of laboratory determined limits with its temperature-dependent
      restriction to deeper water layers in its natural habitat. Thermal responses and
      limits were determined by integrating information from various levels of
      biological organization, including the expression of Hsp70 and Hsp90, the
      phosphorylation of stress-activated protein kinases, p38 mitogen-activated
      protein kinase (p38 MAPK) and cJun-N-terminal kinases (JNKs) as well as metabolic
      adjustments. The latter were assessed by examining temperature effects on the
      activity of the key glycolytic enzyme pyruvate kinase (PK). The expression of
      Hsp70 and Hsp90 was activated when mussels were acclimated to temperatures above
      20 degrees C. Increased phosphorylation of p38 MAPK and JNKs at about the same
      temperatures indicate activation of MAPK signaling cascades and their potential
      involvement in the induction of Hsp genes. As indicated by the activity of PK,
      Modiolus barbatus maintains some aerobic capacity when acclimated to temperatures
      up to 24 degrees C, while further warming probably caused metabolic depression
      and a shift from aerobic to anaerobic metabolism. An increase in mortality
      occurred in parallel, during acclimation to temperatures above 24 degrees C. Our
      results indicate that both the biochemical stress indicators and metabolic status
      respond in parallel once hypoxemia becomes extreme. Comparison with our previous
      study of thermal limits and vertical distribution in M. galloprovincialis
      dwelling in shallow waters emphasizes the relevance of maintained aerobic scope
      over that of passive tolerance for permanent vertical zonation at higher
      temperatures in the field. These findings and conclusions are in line with the
      concept of oxygen and capacity limited thermal tolerance and the associated
      systemic to molecular hierarchy of thermal limitation.

PMID- 18723549
TI  - Acute exacerbation of hemorrhagic rectocolitis during antiangiogenic therapy with
      sunitinib and sorafenib.

PMID- 18723550
TI  - The impact of obesity and diabetes mellitus on the risk of hepatocellular
      carcinoma.
AB  - BACKGROUND: Obesity has been associated to increased hepatocellular carcinoma
      (HCC) risk, but studies on the topic do not fully account for hepatitis B virus
      (HBV) and hepatitis C virus (HCV) infections. Likewise, an increased risk has
      been reported for diabetes mellitus (DM) but whether DM is an independent risk
      factor has not been established yet. To evaluate the association of obesity and
      DM with HCC risk, we conducted a hospital-based, case-control study in two
      Italian areas. PATIENTS AND METHODS: From 1999 to 2003, 185 HCC cases and 404
      hospital controls were enrolled. Blood samples were obtained for HBV and HCV
      screening. RESULTS: After allowance for known risk factors, body mass index >/=30
      kg/m(2) [odds ratio (OR) = 1.9, 95% confidence interval (CI) 0.9-3.9] and DM (OR
      = 3.7, 95% CI 1.7-8.4) were associated to HCC risk. These associations persisted
      (OR = 3.5, 95% CI 1.6-7.7 for obesity; OR = 3.5, 95% CI 1.3-9.2 for DM) among
      subjects without HBV and/or HCV infection. Overall, 23% of HCC cases seemed
      attributable to these conditions, and this figure rose to 37% among subjects
      without HBV and/or HCV infections. CONCLUSIONS: The present study provides
      further evidence that obesity and DM increase HCC risk and that these factors may
      explain a relevant proportion of cases among subjects without markers of HBV/HCV
      infection.

PMID- 18723551
TI  - Serum YKL-40 as a marker for cervical adenocarcinoma.
AB  - BACKGROUND: The current study examined the clinical usefulness of YKL-40 in
      detection and prognosis of uterine cervical cancer. PATIENTS AND METHODS: Serum
      levels of YKL-40, cancer antigen 125 (CA 125), carbohydrate antigen 19-9 (CA19
      9), and squamous cell carcinoma (SCC) antigen were determined by enzyme-linked
      immunosorbent assay in women with benign gynecologic disease (n=24), cervical
      malignancy (SCC, n=104; adenocarcinoma, n=37), and age-matched healthy controls
      (n=45). Immunohistochemical analysis for local YKL-40 expression was carried out
      on 28 adenocarcinomas. RESULTS: Receiver operating characteristic curve analysis
      showed that YKL-40 [area under the curve (AUC)=0.882] was significantly better at
      discriminating adenocarcinoma from healthy control than SCC antigen, CA 125, and
      CA19-9. For SCC, YKL-40 (AUC=0.898) carried out similarly to SCC antigen and was
      better than CA 125 and CA19-9. Using a cut-off YKL-40 value of 92.2 ng/ml,
      sensitivity of YKL-40 in stage I adenocarcinoma (68%) was higher than that of the
      other three markers (11%-21%). Tumor-associated macrophages showed
      immunoreactivity for YKL-40 in 2 of 28 adenocarcinoma tissue samples, but
      adenocarcinoma cells themselves were nonimmunoreactive in all samples.
      Multivariate Cox regression analysis revealed that elevated pretreatment YKL-40
      levels predicted unfavorable prognosis, independent of International Federation
      of Gynecology and Obstetrics stage and age at diagnosis. CONCLUSIONS:
      Pretreatment serum YKL-40 level is a possible prognosticator of cervical
      adenocarcinoma.

PMID- 18723553
TI  - Injury risks associated with tackling in rugby union.
AB  - OBJECTIVE: To examine factors associated with tackles in rugby union and to
      assess their impact on the risk of injury. DESIGN: Two-season (2003/2004 and
      2005/2006) prospective cohort design with video analysis. SETTING: 13 English
      Premiership clubs. PARTICIPANTS: 645 players. MAIN OUTCOME MEASURE: RR (95% CI)
      calculated by comparing the frequency of occurrence of risk factors in a cohort
      of players injured during tackles with their frequency of occurrence in tackles
      in general play. RISK FACTORS: Playing position; player's speed, impact force,
      head position, head/neck flexion and body region struck in the tackle; sequence,
      direction and type of tackle; and location and type of injury. RESULTS: High
      speed going into the tackle, high impact force, collisions and contact with a
      player's head/neck were identified as significant (p<0.01) risk factors for ball
      carriers (BCs) and tacklers. Midfield backs were significantly (p<0.01) more
      prone to injury when tackling than other players. Relatively few tacklers were
      penalised by referees for collision tackles (general play: 2.0%; injured players:
      3.3%) and tackles above the line of the shoulder (general play: 5.9%; injured
      players: 16.7%). CONCLUSIONS: Advice in national and international injury
      prevention programmes for reducing the risk of injury in tackles is strongly
      supported by the results obtained from this study. These programmes should be
      reviewed, however, to provide specific advice for each type of tackle. Stricter
      implementation of the Laws of Rugby relating to collisions and tackles above the
      line of the shoulder may reduce the number of head/neck injuries sustained by
      BCs.

PMID- 18723552
TI  - Need for global action for cancer control.

PMID- 18723554
TI  - Continuing medical education in the 21st century.

PMID- 18723555
TI  - Community treatment orders.

PMID- 18723556
TI  - Are national qualifying examinations a fair way to rank medical students? No.

PMID- 18723557
TI  - Are national qualifying examinations a fair way to rank medical students? Yes.

PMID- 18723559
TI  - Diabetes care needs to focus more on ethnic inequalities, say experts.

PMID- 18723561
TI  - Does tobacco industry marketing excessively impact lesbian, gay and bisexual
      communities?
AB  - BACKGROUND: Tobacco industry documents have revealed marketing plans specifically
      to reach lesbian, gay and bisexual (LGB) populations. Research supports a causal
      linkage between receptivity and exposure to tobacco industry marketing and
      tobacco use uptake among adolescents. Pro-tobacco messages may diminish the
      effectiveness of tobacco control activities and contribute to the high smoking
      prevalence among LGB populations. OBJECTIVE: To compare receptivity and exposure
      to tobacco industry marketing between LGB and heterosexual populations. METHODS:
      Nearly 400 gay or bisexual men and more than 600 lesbian or bisexual women were
      identified in the 2003-2006 Washington State Behavioral Risk Factor Surveillance
      System (BRFSS), a state-wide, population-based telephone survey of adults. The
      BRFSS included questions measuring receptivity and exposure to tobacco industry
      marketing. Multiple logistic regression models stratified by gender were used to
      assess differences for lesbians, gays and bisexuals separately, in comparison to
      their heterosexual counterparts. RESULTS: As expected, smoking prevalence was
      higher among LGB populations than among heterosexuals. After adjustment for
      demographic differences and smoking status, gay and bisexual men reported more
      exposure to tobacco industry marketing (free sample distribution) than straight
      men, but were equally receptive to it. Lesbian and bisexual women were more
      receptive to and reported more exposure to tobacco industry marketing than
      straight women. CONCLUSION: LGB communities, especially lesbian and bisexual
      women, appear to be effectively targeted by tobacco industry marketing
      activities. Strategies to limit tobacco industry marketing, and increase
      individuals' resistance to marketing, may be critical to reducing smoking among
      LGB populations.

PMID- 18723562
TI  - Subcortical damage and white matter disconnection associated with non-fluent
      speech.

PMID- 18723563
TI  - Evaluation of work-related psychosocial factors and regional musculoskeletal
      pain: results from a EULAR Task Force.
AB  - OBJECTIVES: To establish whether review articles provide consistent conclusions
      on associations between workplace psychosocial factors and musculoskeletal pain
      and, if differences exist, to explore whether this is related to the methods
      used. METHODS: Reviews, reported up to February 2007, that included consideration
      of workplace psychosocial factors and upper limb, back or knee pain were
      identified through searches of multiple databases. The specific work-related
      psychosocial factors considered were job demands, support, job autonomy and job
      satisfaction. The conclusions of each review on one or more of the
      psychosocial/musculoskeletal pain associations were extracted. RESULTS: 15 review
      articles were identified that considered one or more of the regional pain
      syndromes included in the study. For back pain, the most consistent conclusions
      (four reviews positive out of six) were with high job demands and low job
      satisfaction. The studies of upper limb pain were exclusively related to shoulder
      and/or neck pain, and the most consistent positive conclusions were with high and
      low job demands (four reviews positive out of six and two reviews positive out of
      three, respectively). For knee pain, only a single review was identified. For
      individual reviews of back and upper limb pain, there were marked differences in
      the number of associations concluded to be positive between reviews. CONCLUSIONS:
      The reasons for reviews coming to different conclusions included that they were
      often evaluating different bodies of evidence (according to their search
      criteria, the year when the review was conducted, the role that quality
      assessment played in whether studies contributed to evidence, and the combination
      of risk factors addressed in individual studies), but more important was whether
      the review specified explicit criteria for making conclusions on strength of
      evidence. These conclusions emphasise the importance of developing standardised
      methods for conducting such evaluations of existing evidence and the importance
      of new longitudinal studies for clarifying the temporal relationship between
      psychosocial factors and musculoskeletal pain in the workplace.

PMID- 18723564
TI  - Serum IgG antibodies to peptidylarginine deiminase 4 predict radiographic
      progression in patients with rheumatoid arthritis treated with tumour necrosis
      factor-alpha blocking agents.
AB  - BACKGROUND: Peptidylarginine deiminase 4 (PAD4) may generate epitopes targeted by
      anticitrullinated protein antibodies in rheumatoid arthritis (RA). A subset of
      patients with RA has serum autoantibodies to human recombinant PAD4 (hPAD4).
      Here, we assessed whether anti-hPAD4 status in RA predicted disease outcome after
      antitumour necrosis factor (anti-TNF)-alpha therapy. METHODS: We analysed RA sera
      obtained at baseline (n = 40) and after 1 year on anti-TNF-alpha therapy (n = 33)
      for anti-hPAD4 IgG. Association analyses between baseline anti-hPAD status and
      disease progression were performed. RESULTS: We found that 17 of 40 patients
      (42.5%) were serum anti-hPAD4 positive at baseline, and the anti-hPAD4 IgG levels
      were stable over 1 year on anti-TNF-alpha therapy. At baseline, there were
      indications that anti-hPAD4 positive patients had more severe disease than the
      negative patients. After 1 year on anti-TNF-alpha therapy, the anti-hPAD4
      positive patients displayed a persistently elevated disease activity score using
      28 joint counts score and increased progression in the van der Heijde-modified
      Sharp erosion score. Accordingly, more anti-hPAD4 positive than negative patients
      presented an increase in van der Heijde-modified Sharp erosion scores >0 over 1
      year. CONCLUSIONS: Anti-hPAD4 IgG can be detected in a subset of RA sera and the
      levels are stable after initiation of anti-TNF-alpha therapy. Serum anti-hPAD4
      may predict persistent disease activity and radiographic progression in patients
      with RA receiving anti-TNF-alpha therapy.

PMID- 18723565
TI  - Sustained changes in lipid profile and macrophage migration inhibitory factor
      levels after anti-tumour necrosis factor therapy in rheumatoid arthritis.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) has recently emerged as
      an important cytokine possibly linking rheumatoid arthritis (RA) and
      atherogenesis. Because atherogenesis is accelerated in RA this study was
      conducted to investigate whether anti-tumour necrosis factor (TNF) therapy could
      lead to sustained downregulation of systemic MIF levels and improvement in lipid
      profiles. METHODS: Fifty RA patients with active disease (disease activity score
      in 28 joints (DAS28) >or=3.2), who started adalimumab therapy at 40 mg every
      other week, were included. At baseline, weeks 16 and 52 serum levels of MIF and
      lipids were assessed. In addition, the DAS28 and serum C-reactive protein (CRP)
      levels and erythrocyte sedimentation rate (ESR) were determined. RESULTS: After
      16 weeks of adalimumab therapy, both DAS28 and MIF levels were significantly
      decreased (p<0.001 and p = 0.020, respectively). This was sustained up to week 52
      (p<0.001 and p = 0.012, respectively). CRP levels and ESR were significantly
      reduced after 16 and 52 weeks of adalimumab therapy (p<0.001). High-density
      lipoprotein cholesterol levels increased at week 16 (p<0.001), but returned to
      baseline at week 52. Apolipoprotein (apo) A-I levels increased at week 16
      (p<0.001) and remained stable (p = 0.005). This resulted in an improved apo B/A-I
      ratio. CONCLUSIONS: The results underline the sustained downregulation of MIF as
      a potential new mechanism by which anti-TNF therapy might reduce vascular
      inflammation, and as such perhaps cardiovascular morbidity in RA patients. This
      hypothesis is supported by an improved apo B/A-I ratio as well as reduced CRP
      levels in these patients.

PMID- 18723567
TI  - Can we really predict the change in serum sodium levels? An analysis of currently
      proposed formulae in hypernatraemic patients.
AB  - BACKGROUND: Hypernatraemia is common in intensive care patients and may present
      an independent risk factor of mortality. Several formulae have been proposed to
      guide infusion therapy for correction of serum sodium. Unfortunately, these
      formulae have never been validated comparatively. We assessed the predictive
      potential of four different formulae (Adrogue-Madias, Barsoum-Levine, Kurtz
      Nguyen and a simple formula based on electrolyte-free water clearance) in
      correction and maintenance of serum sodium in 66 hyper- and normonatraemic ICU
      patients. METHODS: With daily measurements of sodium/potassium and
      fluid/electrolyte balances, a day-to-day prediction of serum sodium levels was
      calculated using the four formulae. This was compared to the measured changes in
      serum sodium. RESULTS: Six hundred and eighty-one patient-days (194
      hypernatraemic) in 66 patients were available for calculations. Prediction of
      serum sodium levels using all four formulae correlated significantly (P < 0.05)
      with measured changes in serum sodium. Individual variations were extreme, and
      the mean differences (+/-SD) for predicted versus measured serum sodium were
      within the range of 3.4-4.5 (+/-4.4-4.7) mmol/l similar for the Adrogue-Madias,
      Barsoum-Levine and Nguyen-Kurtz formulae. In comparison, our proposed formula
      underestimated the changes of serum sodium (mean +/- SD -1.5 +/- 5.3). During
      hypernatraemia, the differences between predicted and measured values were even
      greater (mean +/- SD 5.0-6.7 +/- 3.9-4.3) using the published formulae compared
      to our formula (mean +/- SD 0.2 +/- 4.0). CONCLUSIONS: Currently available
      formulae to guide infusion therapy in hyper- and normonatraemic states do not
      accurately predict changes of serum sodium in the individual ICU patient. In
      clinical practice, infusion therapy should be based on the reasons for
      hypernatraemia and serial measurements of serum sodium to avoid evolution of
      derangements.

PMID- 18723568
TI  - Conversion from epoetin beta to darbepoetin: what is the equivalent dose?

PMID- 18723566
TI  - Association of multiple behavioral risk factors with adolescents' willingness to
      engage in eHealth promotion.
AB  - OBJECTIVE: This study examines adolescents' willingness to use the internet and
      other forms of technology for health promotion purposes (i.e., "eHealth
      promotion" willingness) and determines if a relationship exists between
      adolescents' behavioral risks and their eHealth promotion willingness. METHODS: A
      total of 332 adolescents provided data at a routine medical check-up, including
      assessments of technology access, eHealth promotion willingness, and multiple
      behavioral risk factors for child- and adult-onset disease (body mass index,
      physical activity, smoking, sun protection, depression). RESULTS: The level of
      access to technology among the sample was high, with moderate willingness to
      engage in eHealth promotion. After adjusting for adolescents' access to
      technology, the presence of multiple behavioral risk factors was positively
      associated with willingness to use technology for health promotion purposes (beta
      =.12, p =.03). CONCLUSIONS: Adolescents with both single and multiple behavioral
      risk factors are in need of health promotion to prevent the onset of disease
      later in life. eHealth appears to be an acceptable and promising intervention
      approach with this population.

PMID- 18723569
TI  - Enhanced clearance of highly protein-bound drugs by albumin-supplemented
      dialysate during modeled continuous hemodialysis.
AB  - BACKGROUND: In 2006, there were 16 796 toxic exposures attributed to valproic
      acid (VPA), carbamazepine (CBZ) and phenytoin (PHT) reported to the US Toxic
      Exposure Surveillance System. Of these, 30% (5046) were treated in a health care
      facility with 12 cases resulting in death. These drugs are highly protein bound
      and poorly dialyzable; however, it has been suggested that albumin-supplemented
      dialysate may enhance dialytic clearance. We investigated whether the addition of
      albumin to dialysate affects dialytic clearance of VPA, CBZ and PHT. METHODS:
      VPA, CBZ and PHT were added to a bovine blood-based in vitro continuous
      hemodialysis circuit, which included a polysulfone or an AN69 hemodialyzer. VPA,
      CBZ and PHT clearances were calculated from spent dialysate and pre-dialyzer
      plasma concentrations. VPA, CBZ and PHT clearances with control (albumin-free)
      dialysate were compared to clearances achieved with 2.5% or 5% human albumin
      containing dialysate. The influences of blood flow (180 and 270 mL/min) and
      dialysate flow (1, 2 and 4 L/h) on dialysis clearance were also assessed.
      RESULTS: The addition of 2.5% albumin to dialysate significantly enhanced
      dialytic clearance of VPA and CBZ, but not PHT. Use of 5% albumin dialysate
      further increased VPA and CBZ clearance. Overall, drug clearance was related
      directly to dialysate flow but independent of blood flow. CONCLUSION: Continuous
      hemodialysis with albumin-supplemented dialysate significantly enhanced VPA and
      CBZ, but not PHT, clearance compared to control dialysate. Continuous
      hemodialysis with albumin-supplemented dialysate may be a promising therapy to
      enhance dialytic clearance of selected highly protein-bound drugs.

PMID- 18723570
TI  - Mycophenolic acid inhibits the autocrine PDGF-B synthesis and PDGF-BB-induced
      mRNA expression of Egr-1 in rat mesangial cells.
AB  - BACKGROUND: Uncontrolled mesangial cell (MC) proliferation within the context of
      glomerular disease contributes to the development of glomerulosclerosis.
      Mesangial autocrine growth factor stimulation has been described as a pathogenic
      factor. We investigated the effects of mycophenolic acid (MPA), the active
      metabolite of the immunosuppressant mycophenolate mofetil (MMF), on proliferation
      factors of cultured rat MCs. MPA was tested on the expression of platelet-derived
      growth factor-B (PDGF-B) and its receptor beta (PDGFR-beta), the immediate early
      gene (IEG) c-fos and the early growth response gene-1 (Egr-1), and AP-1
      activation. METHODS: Growth-arrested rat MCs were stimulated with 10% fetal calf
      serum (FCS) or 10-25 ng/ml platelet-derived growth factor-BB (PDGF-BB) in the
      presence or absence of MPA (0.019-10 microM) with or without guanosine (100
      microM). MC proliferation was quantified by 5-bromo-2'-deoxyuridine (BrdU)
      incorporation and direct cell counting. Cytotoxicity of MPA was evaluated using
      the MTT and LDH tests. Protein expression of PDGF-B and its receptor PDGFR-beta
      was quantified by western blot analysis. The effect of MPA on gene expression of
      PDGF-B, Egr-1 and c-fos was determined by the reverse transcriptase-polymerase
      chain reaction (RT-PCR). AP-1 activation was analysed by an electrophoretic
      mobility shift assay (EMSA). RESULTS: Exposure of MCs to MPA caused a
      concentration-dependent inhibition of FCS-induced cell proliferation (cell number
      increase) with an IC50 of 0.44 +/- 0.03 microM and DNA synthesis with an IC50 of
      0.52 +/- 0.02 microM without cell cytotoxicity in the therapeutic range. MPA
      decreased the PDGF-B protein expression and mRNA self-induction of PDGF-B but did
      not alter the protein expression of PDGFR-beta. MPA strongly inhibited the PDGF
      BB-induced mRNA expression of Egr-1 decreasing to 7.6 +/- 2.5% after 30 min (P
      <or= 0.001) and to 4.7 +/- 3.1% after 1 h (P <or= 0.05), both being compared to
      the maximal expression induced by PDGF-BB. PDGF-BB-induced c-fos expression under
      MPA was unchanged after 30 min and decreased to 57 +/- 26% after 1 h (n.s.). MPA
      treatment did not affect PDGF-BB-induced AP-1 activity determined after 1 h and 2
      h. The inhibitory MPA effect on PDGF-BB-induced PDGF-B expression was not
      significantly restored by guanosine (56 +/- 18% versus 32 +/- 17% after 2 h,
      n.s.), and MPA inhibition of PDGF-BB-induced Egr-1 expression was not reversed by
      exogenous guanosine. CONCLUSIONS: Treatment of cultured MCs with MPA inhibits MC
      proliferation correlating with a downregulation of the PDGF-B gene and protein
      expression and a suppression of Egr-1 mRNA expression. Since exogenous guanosine
      was not able to reverse the inhibitory MPA effect on PDGF-B and Egr-1 expression,
      we conclude that the antiproliferative effect of MPA on MCs may not solely depend
      on dGTP depletion but on a specific interference with the autocrine PDGF-B
      synthesis and Egr-1 expression of MCs.

PMID- 18723571
TI  - CD4+CD25+ T-cell populations expressing CD134 and GITR are associated with
      disease activity in patients with Wegener's granulomatosis.
AB  - BACKGROUND: An increased CD4(+) CD25(+) T-cell population is observed in
      Wegener's granulomatosis (WG). This T-cell population is not well characterized
      yet and their contribution to the disease pathogenesis remains obscure. METHODS:
      Thirty patients with WG and 18 healthy controls (HC) were included in this study.
      The disease activity and extension were measured by the Birmingham Vasculitis
      Activity Score (BVAS) and the Disease Extent Index (DEI). Lymphocytes from
      peripheral blood were analysed by FACS for the expression of CD4, CD25, CD134 and
      GITR. Cytokine expression in these subsets was assessed too. Nasal, lung and
      renal tissues from WG patients were immunohistochemically stained for CD3 and
      CD134. RESULTS: The percentage of CD134(+) as well as GITR(+) expressing
      CD4(+)CD25(+) lymphocytes was increased in patients as compared to HC (37 +/- 12%
      versus 27 +/- 8%, P = 0.005; 18 +/- 9% versus 11 +/- 6%, P = 0.003). The
      expression of CD134 and GITR showed a significant correlation with disease
      activity (r = 0.5, P = 0.009; r = 0.55, P = 0.001). Most of these displayed the
      phenotype of effector memory T-cells (94 +/- 4% and 91 +/- 6%). CD134 T-cells
      were found in tissues affected by WG. CONCLUSIONS: CD4(+)CD25(+) effector memory
      T-cells expressing CD134 and GITR seem to play a role in disease mechanisms, as
      suggested by their close association with disease activity and their
      participation in inflammatory process.

PMID- 18723572
TI  - Clerocidin selectively modifies the gyrase-DNA gate to induce irreversible and
      reversible DNA damage.
AB  - Clerocidin (CL), a microbial diterpenoid, reacts with DNA via its epoxide group
      and stimulates DNA cleavage by type II DNA topoisomerases. The molecular basis of
      CL action is poorly understood. We establish by genetic means that CL targets DNA
      gyrase in the gram-positive bacterium Streptococcus pneumoniae, and promotes
      gyrase-dependent single- and double-stranded DNA cleavage in vitro. CL-stimulated
      DNA breakage exhibited a strong preference for guanine preceding the scission
      site (-1 position). Mutagenesis of -1 guanines to A, C or T abrogated CL cleavage
      at a strong pBR322 site. Surprisingly, for double-strand breaks, scission on one
      strand consistently involved a modified (piperidine-labile) guanine and was not
      reversed by heat, salt or EDTA, whereas complementary strand scission occurred at
      a piperidine-stable -1 nt and was reversed by EDTA. CL did not induce cleavage by
      a mutant gyrase (GyrA G79A) identified here in CL-resistant pneumococci. Indeed,
      mutations at G79 and at the neighbouring S81 residue in the GyrA breakage-reunion
      domain discriminated poisoning by CL from that of antibacterial quinolones. The
      results suggest a novel mechanism of enzyme inhibition in which the -1 nt at the
      gyrase-DNA gate exhibit different CL reactivities to produce both irreversible
      and reversible DNA damage.

PMID- 18723573
TI  - An artificial processivity clamp made with streptavidin facilitates oriented
      attachment of polymerase-DNA complexes to surfaces.
AB  - Single molecule analysis of individual enzymes can require oriented
      immobilization of the subject molecules on a detection surface. As part of a
      technology development project for single molecule DNA sequencing, we faced the
      multiple challenges of immobilizing both a DNA polymerase and its DNA template
      together in an active, stable complex capable of highly processive DNA synthesis
      on a nonstick surface. Here, we report the genetic modification of the archaeal
      DNA polymerase 9 degrees N in which two biotinylated peptide 'legs' are inserted
      at positions flanking the DNA-binding cleft. Streptavidin binding on either side
      of the cleft both traps the DNA template in the polymerase and orients the
      complex on a biotinylated surface. We present evidence that purified polymerase
      DNA-streptavidin complexes are active both in solution and immobilized on a
      surface. Processivity is improved from <20 nt in the unmodified polymerase to
      several thousand nucleotides in the engineered complexes. High-molecular weight
      DNA synthesized by immobilized complexes is observed moving above the surface
      even as it remains tethered to the polymerase. Pre-formed polymerase-DNA
      streptavidin complexes can be stored frozen and subsequently thawed without
      dissociation or loss of activity, making them convenient for use in single
      molecule analysis.

PMID- 18723574
TI  - Accurate taxonomy assignments from 16S rRNA sequences produced by highly parallel
      pyrosequencers.
AB  - The recent introduction of massively parallel pyrosequencers allows rapid,
      inexpensive analysis of microbial community composition using 16S ribosomal RNA
      (rRNA) sequences. However, a major challenge is to design a workflow so that
      taxonomic information can be accurately and rapidly assigned to each read, so
      that the composition of each community can be linked back to likely ecological
      roles played by members of each species, genus, family or phylum. Here, we use
      three large 16S rRNA datasets to test whether taxonomic information based on the
      full-length sequences can be recaptured by short reads that simulate the
      pyrosequencer outputs. We find that different taxonomic assignment methods vary
      radically in their ability to recapture the taxonomic information in full-length
      16S rRNA sequences: most methods are sensitive to the region of the 16S rRNA gene
      that is targeted for sequencing, but many combinations of methods and rRNA
      regions produce consistent and accurate results. To process large datasets of
      partial 16S rRNA sequences obtained from surveys of various microbial
      communities, including those from human body habitats, we recommend the use of
      Greengenes or RDP classifier with fragments of at least 250 bases, starting from
      one of the primers R357, R534, R798, F343 or F517.

PMID- 18723575
TI  - Time-independent maternal and infant factors and time-dependent infant
      morbidities including HIV infection, contribute to infant growth faltering during
      the first 2 years of life.
AB  - Studies investigating the predictors of growth in infants born to HIV-infected
      women in developing countries are limited. Using data from 886 Tanzanian HIV
      infected women and their infants, we examined the impact of maternal
      socioeconomic and immunological status, infant characteristics at birth, and HIV,
      diarrhea and respiratory infections on infants' monthly length-for-age (LAZ) and
      length-for-weight (WLZ) z-scores during the first 2 years of life. We used
      restricted cubic splines to estimate average adjusted growth curves by categories
      of each predictor. LAZ decreased significantly during the first 2 years. WLZ
      increased from birth to 4 months but decreased significantly thereafter. Greater
      maternal schooling significantly reduced deterioration in LAZ and WLZ scores from
      birth to 24 months, while maternal CD4 cell counts >or=200 mm(-3) at baseline
      were associated with reduced deterioration in LAZ scores. Infants born pre-term
      or with low-birth weight were significantly more stunted and wasted than their
      reference groups at all time points though their rate of growth faltering was
      slower. Infant-HIV status was strongly associated with significantly greater
      deterioration in LAZ and WLZ scores, beginning at about 4 months of age. Episodes
      of diarrhea or respiratory infections were related to significantly lower WLZ but
      not LAZ scores, independent of infant-HIV status. In conclusion, maternal
      schooling, immunological status and infant infections are important predictors of
      early growth in children born to HIV-positive women.

PMID- 18723576
TI  - From Guard to Decoy: a new model for perception of plant pathogen effectors.
AB  - The Guard Model for disease resistance postulates that plant resistance proteins
      act by monitoring (guarding) the target of their corresponding pathogen effector.
      We posit, however, that guarded effector targets are evolutionarily unstable in
      plant populations polymorphic for resistance (R) genes. Depending on the absence
      or presence of the R gene, guarded effector targets are subject to opposing
      selection forces (1) to evade manipulation by effectors (weaker interaction) and
      (2) to improve perception of effectors (stronger interaction). Duplication of the
      effector target gene or independent evolution of a target mimic could relax
      evolutionary constraints and result in a decoy that would be solely involved in
      effector perception. There is growing support for this Decoy Model from four
      diverse cases of effector perception involving Pto, Bs3, RCR3, and RIN4. We
      discuss the differences between the Guard and Decoy Models and their variants,
      hypothesize how decoys might have evolved, and suggest ways to challenge the
      Decoy Model.

PMID- 18723577
TI  - Type B response regulators of Arabidopsis play key roles in cytokinin signaling
      and plant development.
AB  - The type B Arabidopsis Response Regulators (ARRs) of Arabidopsis thaliana are
      transcription factors that act as positive regulators in the two-component
      cytokinin signaling pathway. We employed a mutant-based approach to perform a
      detailed characterization of the roles of ARR1, ARR10, and ARR12 in plant growth
      and development. The most pronounced phenotype was found in the arr1-3 arr10-5
      arr12-1 triple loss-of-function mutant, which showed almost complete
      insensitivity to high levels of exogenously applied cytokinins. The triple mutant
      exhibited reduced stature due to decreased cell division in the shoot, enhanced
      seed size, increased sensitivity to light, altered chlorophyll and anthocyanin
      concentrations, and an aborted primary root with protoxylem but no metaxylem.
      Microarray analysis revealed that expression of the majority of cytokinin
      regulated genes requires the function of ARR1, ARR10, and ARR12. Characterization
      of double mutants revealed differing contributions of the type B ARRs to mutant
      phenotypes. Our results support a model in which cytokinin regulates a wide array
      of downstream responses through the action of a multistep phosphorelay that
      culminates in transcriptional regulation by ARR1, ARR10, and ARR12.

PMID- 18723578
TI  - RACK1 functions in rice innate immunity by interacting with the Rac1 immune
      complex.
AB  - A small GTPase, Rac1, plays a key role in rice (Oryza sativa) innate immunity as
      part of a complex of regulatory proteins. Here, we used affinity column
      chromatography to identify rice RACK1 (for Receptor for Activated C-Kinase 1) as
      an interactor with Rac1. RACK1 functions in various mammalian signaling pathways
      and is involved in hormone signaling and development in plants. Rice contains two
      RACK1 genes, RACK1A and RACK1B, and the RACK1A protein interacts with the GTP
      form of Rac1. Rac1 positively regulates RACK1A at both the transcriptional and
      posttranscriptional levels. RACK1A transcription was also induced by a fungal
      elicitor and by abscisic acid, jasmonate, and auxin. Analysis of transgenic rice
      plants and cell cultures indicates that RACK1A plays a role in the production of
      reactive oxygen species (ROS) and in resistance against rice blast infection.
      Overexpression of RACK1A enhances ROS production in rice seedlings. RACK1A was
      shown to interact with the N terminus of NADPH oxidase, RAR1, and SGT1, key
      regulators of plant disease resistance. These results suggest that RACK1A
      functions in rice innate immunity by interacting with multiple proteins in the
      Rac1 immune complex.

PMID- 18723579
TI  - Angiotensin II stimulates water and NaCl intake through separate cell signalling
      pathways in rats.
AB  - Angiotensin II (AngII) stimulation of water and NaCl intake is a classic model of
      the behavioural effects of hormones. In vitro studies indicate that the AngII
      type 1 (AT(1)) receptor stimulates intracellular pathways that include protein
      kinase C (PKC) and mitogen-activated protein (MAP) kinase activation. Previous
      studies support the hypotheses that PKC is involved in AngII-induced water, but
      not NaCl intake and that MAP kinase plays a role in NaCl consumption, but not
      water intake, after injection of AngII. The present experiments test these
      hypotheses in rats using central injections of AngII in the presence or absence
      of a PKC inhibitor or a MAP kinase inhibitor. Pretreatment with the PKC inhibitor
      chelerythrine attenuated AngII-induced water intake, but NaCl intake was
      unaffected. In contrast, pretreatment with U0126, a MAP kinase inhibitor, had no
      effect on AngII-induced water intake, but attenuated NaCl intake. These data
      support the working hypotheses and significantly extend our earlier findings and
      those of others. Perhaps more importantly, these experiments demonstrate the
      remarkable diversity of peptide receptor systems and add support for the
      surprising finding that intracellular signalling pathways can have divergent
      behavioural relevance.

PMID- 18723580
TI  - Purinergic cotransmission.
AB  - Adenosine 5'-triphosphate (ATP) is a cotransmitter with classical transmitters in
      most nerves in the peripheral and central nervous systems, although the
      proportions vary between tissues and species and in different developmental and
      pathophysiological circumstances. There was early evidence that ATP was released
      together with acetylcholine (ACh) from motor nerves supplying skeletal muscle,
      although it was considered at the time as a molecule involved in the vesicular
      uptake and storage of ACh. Later it was shown that in the developing
      neuromuscular junction, released ATP acted on P2X receptor ion channels as a
      genuine cotransmitter with ACh. Adenosine triphosphate was shown to be released
      from sympathetic nerves supplying the guinea-pig taenia coli in 1971. Soon after,
      the possibility was raised that ATP was coreleased with noradrenaline from
      sympathetic nerves to guinea-pig seminal vesicle, cat nictitating membrane and
      guinea-pig vas deferens. Sympathetic purinergic cotransmission has also been
      demonstrated in many blood vessels. Parasympathetic nerves supplying the urinary
      bladder use ACh and ATP as cotransmitters; ATP acts through P2X ionotropic
      receptors, whereas the slower component of the response is mediated by the
      metabotropic muscarinic receptor. Adenosine triphosphate and glutamate appear to
      be cotransmitters in primary afferent sensory neurons. Adenosine triphosphate,
      calcitonin gene-related peptide and substance P coexist in some sensory-motor
      nerves. A subpopulation of intramural enteric nerves provides non-adrenergic, non
      cholinergic inhibitory innervation of gut smooth muscle. Three cotransmitters are
      involved, namely ATP, nitric oxide and vasoactive intestinal polypeptide. In
      recent years, studies have shown that ATP is released with ACh, noradrenaline,
      glutamate, gamma-aminobutyric acid, 5-hyroxytryptamine and dopamine in different
      subpopulations of neurons in the central nervous system.

PMID- 18723581
TI  - Cardiac and coronary function in the Langendorff-perfused mouse heart model.
AB  - The Langendorff mouse heart model is widely employed in studies of myocardial
      function and responses to injury (e.g. ischaemia). Nonetheless, marked
      variability exists in its preparation and functional properties. We examined the
      impact of early growth (8, 16, 20 and 24 weeks), sex, perfusion fluid [Ca(2+)]
      and pacing rate on contractile function and responses to 20 min ischaemia
      followed by 45 min reperfusion. We also assessed the impact of strain, and tested
      the utility of the model in studying coronary function. Under normoxic
      conditions, hearts from 8-week-old male C57BL/6 mice (2 mm free perfusate
      [Ca(2+)], 420 beats min(-1)) exhibited 145 +/- 2 mmHg left ventricular developed
      pressure (LVDP). Force development declined by approximately 15% (126 +/- 5 mmHg)
      with a reduction in free [Ca(2+)] to 1.35 mm, and by 25% (108 +/- 3 mmHg) with
      increased pacing to 600 beats min(-1). While elevated heart rate failed to modify
      ischaemic outcome, the lower [Ca(2+)] significantly improved contractile recovery
      (by >30%). We detected minimal sex-dependent differences in normoxic function
      between 8 and 24 weeks, although age modified contractile function in males
      (increased LVDP at 24 versus 8 weeks) but not females. Both male and female
      hearts exhibited age-related reductions in ischaemic tolerance, with a
      significant decline in recovery evident at 16 weeks in males and later, at 20-24
      weeks, in females (versus recoveries in hearts at 8 weeks). Strain also modified
      tolerance to ischaemia, with similar responses in hearts from C57BL/6, 129/sv,
      Quackenbush Swiss and FVBN mice, but substantially greater tolerance in BALB/c
      hearts. In terms of vascular function, baseline coronary flow (20-25 ml min(-1)
      g(-1)) was 50-60% of maximally dilated flows, and coronary reactive and
      functional hyperaemic responses were pronounced (up to 4-fold elevations in flow
      in hearts lacking ventricular balloons). These data indicate that attention to
      age (and sex) of mice will reduce variability in contractile function and
      ischaemic responses. Even small differences in perfusion fluid [Ca(2+)] also
      significantly modify tolerance to ischaemia (whereas modest shifts in heart rate
      do not impact). Ischaemic responses are additionally strain dependent, with
      BALB/c hearts displaying greatest intrinsic tolerance. Finally, the model is
      applicable to the study of vascular reactivity, providing large responses and
      excellent reproducibility.

PMID- 18723582
TI  - Management of acute bronchiolitis: can evidence based guidelines alter clinical
      practice?
AB  - BACKGROUND: Acute bronchiolitis is the most common lower respiratory tract
      infection in infants and there is no evidence that drug treatment alters its
      natural course. Despite this, most Swiss paediatricians reported in 2001
      prescribing bronchodilators and inhaled corticosteroids (ICS). This situation led
      to the creation of national guidelines followed by a tailored implementation
      programme. The aim of this study was to examine if treatment practices changed
      after the implementation of the new guidelines. METHODS: A questionnaire on
      treatment of bronchiolitis was sent to all Swiss paediatricians before (2001) and
      after (2006) creation and implementation of national guidelines (2003-2005).
      Guidelines were created in collaboration with all paediatric pulmonologists and
      implemented carefully using a multifaceted approach. RESULTS: Questionnaires were
      returned by 541 paediatricians (58%) in 2001 and by 639 (54%) in 2006. While both
      surveys showed a wide variation in the treatment of bronchiolitis between
      physicians, reported drug prescription decreased significantly between the two
      surveys. For outpatients, general use (for all patients) of bronchodilators
      dropped from 60% to 23%, and general use of ICS from 34% to 6%. For inpatients,
      general use of bronchodilators and ICS dropped from 55% to 18% and from 26% to
      6%, respectively (all p<0.001). The decrease was evident in all regions, among
      hospital and primary care physicians, and among general paediatricians and
      paediatric pulmonologists. CONCLUSIONS: National guidelines together with a
      tailored implementation programme can have a major impact on medical management
      practices in a country.

PMID- 18723583
TI  - Heterogeneity in the spatial distribution of bacterial sexually transmitted
      infections.
AB  - OBJECTIVES: Detailed knowledge of the spatial distribution of disease is required
      to inform service delivery and plan effective interventions. In order to
      elucidate the spatial epidemiology of three common sexually transmitted
      infections (STI) further, any significant spatiotemporal clustering of
      gonorrhoea, chlamydia or syphilis cases in New South Wales (NSW) was detected and
      described. METHODS: Eleven years of notified STI case data were analysed.
      Calculation of age and sex-stratified incidence rates was followed by
      spatiotemporal cluster analyses to investigate differences in the epidemiology of
      gonorrhoea, chlamydia and syphilis. RESULTS: More than one-third of all
      gonorrhoea, chlamydia and syphilis cases in NSW were detected within cluster
      areas. Gonorrhoea cases were the most highly clustered, followed by syphilis,
      then chlamydia. Clusters were highly significant and relative risk estimates
      ranged from 1.6 to 22.9. CONCLUSION: The findings establish the high degree of
      geographical heterogeneity in STI incidence in NSW and indicate that the postal
      area of residence is an important predictor of STI incidence. Geographical
      surveillance could be incorporated into routine STI surveillance to identify
      populations in need of intervention. The evidence presented in this report
      indicates a need to implement geography-specific and phase-appropriate STI
      prevention and control strategies.

PMID- 18723584
TI  - Can text messaging results reduce time to treatment of Chlamydia trachomatis?
AB  - We assessed the impact of text messaging as the preferred method of communicating
      positive Chlamydia trachomatis test results in an urban sexual health clinic.
      Following the introduction of a text messaging service to communicate positive C
      trachomatis test results to patients, the time between test and treatment in 293
      consecutive patients was compared with 303 historic controls. No significant
      difference was found in either median time to treatment for all patients (3 days
      in 2005; 4 days in 2007) or median time to treatment (both 7 days) for those not
      treated immediately. There was no significant difference in time to treatment
      between those using a landline or mobile phone. Mobile phone use was
      significantly higher in 2007. Overall, we treated more cases within 4 weeks in
      2007 (98.6% cf 96%). The lack of difference in time to treatment showed the use
      of this technology is as effective as more traditional means of communication.
      The increase in cases of C trachomatis treated within 4 weeks may reflect the
      significant increase in mobile phone use and improved ability to contact people
      rather than simply the introduction of text messaging.

PMID- 18723585
TI  - Missing pelvic inflammatory disease? Substantial differences in the rate at which
      doctors diagnose PID.
AB  - OBJECTIVES: The clinical diagnosis of pelvic inflammatory disease (PID) is
      subjective. Our aim was to determine if the pattern of diagnosis of PID among
      experienced clinicians varied compared with the diagnosis of genital warts.
      METHODS: We conducted a retrospective study of 325 PID diagnoses made by
      experienced clinicians at Melbourne Sexual Health Centre, Australia (2002-2006),
      where doctors saw 21 785 unselected female patients in a walk-in service. We
      compared the proportion of female patients diagnosed as having PID and genital
      warts between doctors and then compared doctors above (high diagnosing) and below
      (low diagnosing) the mean rate of PID diagnosis. RESULTS: There were significant
      and clinically important differences in the proportion of women diagnosed with
      having PID (0-5.7%) across 23 doctors investigated. Estimated standard deviation
      in the frequency of PID diagnosis (logit scale) was 1.26 (95% CI 0.81 to 1.95)-
      approximately four times greater than for warts. Patients seen by high (n = 4673)
      and low (n = 16 787) diagnosing doctors had similar epidemiological risk profiles
      suggesting true distribution of PID cases across doctors was similar (p>0.13).
      Women diagnosed with having PID by high diagnosing doctors compared with low
      diagnosing doctors were younger (odds ratio 1.7; 95% CI 1.1 to 2.8, p = 0.013)
      but otherwise had similar epidemiological and clinical features. CONCLUSIONS:
      Differences in diagnostic rates for PID between doctors are substantial and may
      be because of PID cases being missed by some doctors.

PMID- 18723586
TI  - Negative vascular remodelling after implantation of bioabsorbable magnesium alloy
      stents in porcine coronary arteries: a randomised comparison with bare-metal and
      sirolimus-eluting stents.
AB  - OBJECTIVE: We sought to assess vascular remodelling and neointima formation after
      implantation of bioabsorbable magnesium alloy stents (AMS). DESIGN: Randomised
      experimental study. INTERVENTIONS: AMS (n = 11), sirolimus-eluting stents
      (Cypher; n = 11) and bare-metal stents (BMS; n = 9) were randomly implanted in 31
      porcine coronary arteries (n = 11 pigs). MAIN OUTCOME MEASURES: Neointima
      formation was measured by histomorphometry at 90 days. Vascular remodelling
      defined as change in external elastic membrane area from index intervention to
      follow-up was assessed by serial intravascular ultrasound (IVUS). RESULTS: By
      histomorphometry, lumen (median (quartiles); AMS: 1.75 mm2 (1.07-3.26), Cypher
      2.52 mm2 (2.22-5.01), BMS 4.55 mm2 (3.2-7.44); p = 0.013) and external elastic
      membrane area (AMS: 5.56 mm2 (4.09-6.95), Cypher 7.95 mm2 (6.45-10.92), BMS 9.08
      mm2 (7.85-11.63); p = 0.014) were smallest after AMS implantation. By IVUS,
      external elastic membrane area at follow-up was smallest (AMS: 7.5 (2.8) mm2,
      Cypher 9.1 (2.7) mm2, BMS 9.9 (3.1) mm2; p = 0.33) and change in external elastic
      membrane area from index intervention to follow-up (remodelling; AMS: -1.0 (3.1)
      mm2, Cypher 1.0 (0.8) mm2, BMS 0.9 (1.2) mm2; p = 0.30) was greatest in the AMS
      group. In a dichotomised IVUS assessment of vascular remodelling, six AMS stents
      were remodelled (negative remodelling: n = 5; positive remodelling: n = 1) at 90
      day follow-up (AMS versus Cypher + BMS: p = 0.001). Neointima formation was
      smallest in the AMS group (p<0.05 for both histomorphometry and IVUS).
      CONCLUSION: Coronary implantation of absorbable magnesium stents, compared to two
      non-absorbable stents, was associated with the smallest lumen area at three-month
      follow-up because of negative vascular remodelling.

PMID- 18723587
TI  - The social behaviours of bacterial pathogens.
AB  - INTRODUCTION: The term quorum sensing (QS) is used to describe communication
      between bacterial cells, whereby a coordinated population response is controlled
      by diffusible signal molecules produced by individuals. SOURCES OF DATA: Studies
      on QS-mediated signalling processes in bacteria have revealed the existence of
      intricate regulatory networks to enable bacterial populations to fine tune their
      responses to environmental changes and increase their chances of survival, using
      complex signalling pathways. AREAS OF AGREEMENT: A population of bacteria
      invading a host may benefit from the coordinated release of virulence
      determinants and in vitro studies have shown that QS regulates virulence factor
      production in many species of bacteria. AREAS OF CONTROVERSY: However, the role
      of QS in vivo is less well understood, but has been demonstrated to be important
      in several pathogenic organisms. GROWING POINTS AND AREAS TIMELY FOR DEVELOPING
      RESEARCH: There is a growing interest in blocking bacterial cell-cell
      communication as a means to control infections. This review discusses QS from a
      pathogenic perspective and discusses the potential of QS as an anti-pathogenic
      target.

PMID- 18723588
TI  - Updates on improvement of human athletic performance: focus on world records in
      athletics.
AB  - INTRODUCTION: Progression of world records (WRs) in athletics is a reliable mean
      to assess the potentiality of the human body, which also reflects how society has
      evolved over time and will continue to evolve. We conducted a quantitative
      analysis of WRs in measurable Olympic events from nine representative disciplines
      (100, 400, 1500, 10,000 m, marathon, long jump, high jump, shot put and javelin
      throw) in order to identify progression and trends. SOURCES OF DATA: Data were
      gathered for the years 1900-2007 from the database of the International Olympic
      Committee. AREAS OF AGREEMENT: Overall, the relative improvement of athletic
      performance was higher in women than in men, being nearly doubled across the
      different specialities. The biggest increases were observed for javelin throw and
      shot put, in both men and women, respectively. Conversely, the improvement in
      race time was directly related to the race distance. We also observed a
      consistent significant linear model of WRs progression in time, although the
      improvement has substantially stopped or reached a plateau in several
      specialities. GROWING POINTS: The observed trend might be explained by a variety
      of factors, including social and environmental changes, natural selection,
      advances in training and sport physiology, ergogenic aids and, possibly, doping.
      EMERGING AREAS FOR DEVELOPING RESEARCH: These results are discussed in a
      multifaceted approach, taking into account several biological, environmental and
      technological issues that might explain the trends observed.

PMID- 18723589
TI  - Efficiency of histidine-associating compounds for blocking the alzheimer's Abeta
      channel activity and cytotoxicity.
AB  - The opening of the Alzheimer's Abeta channel permits the flux of calcium into the
      cell, thus critically disturbing intracellular ion homeostasis. Peptide segments
      that include the characteristic histidine (His) diad, His(13) and His(14),
      efficiently block the Abeta channel activity, blocking Abeta cytotoxicity. We
      hypothesize that the vicinal His-His peptides coordinate with the rings of His in
      the mouth of the pore, thus blocking the flow of calcium ions through the
      channel, with consequent blocking of Abeta cytotoxicity. To test this hypothesis,
      we studied Abeta ion channel activity and cytotoxicity after the addition of
      compounds that are known to have His association capacity, such as Ni(2+),
      imidazole, His, and a series of His-related compounds. All compounds were
      effective at blocking both Abeta channel and preventing Abeta cytotoxicity. The
      efficiency of protection of His-related compounds was correlated with the number
      of imidazole side chains in the blocker compounds. These data reinforce the
      premise that His residues within the Abeta channel sequence are in the pathway of
      ion flow. Additionally, the data confirm the contribution of the Abeta channel to
      the cytotoxicity of exogenous Abeta.

PMID- 18723590
TI  - High-speed high-resolution imaging of intercellular immune synapses using optical
      tweezers.
AB  - Imaging in any plane other than horizontal in a microscope typically requires a
      reconstruction from multiple optical slices that significantly decreases the
      spatial and temporal resolution that can be achieved. This can limit the
      precision with which molecular events can be detected, for example, at
      intercellular contacts. This has been a major issue for the imaging of immune
      synapses between live cells, which has generally required the reconstruction of
      en face intercellular synapses, yielding spatial resolution significantly above
      the diffraction limit and updating at only a few frames per minute. Strategies to
      address this issue have usually involved using artificial activating substrates
      such as antibody-coated slides or supported planar lipid bilayers, but synapses
      with these surrogate stimuli may not wholly resemble immune synapses between two
      cells. Here, we combine optical tweezers and confocal microscopy to realize
      generally applicable, high-speed, high-resolution imaging of almost any arbitrary
      plane of interest. Applied to imaging immune synapses in live-cell conjugates,
      this has enabled the characterization of complex behavior of highly dynamic
      clusters of T cell receptors at the T cell/antigen-presenting cell intercellular
      immune synapse and revealed the presence of numerous, highly dynamic long
      receptor-rich filopodial structures within inhibitory Natural Killer cell immune
      synapses.

PMID- 18723591
TI  - Functional halt positions of rotary FOF1-ATPase correlated with crystal
      structures.
AB  - The F(O)F(1)-ATPase is a rotary molecular motor. Driven by ATP-hydrolysis, its
      central shaft rotates in 80 degrees and 40 degrees steps, interrupted by
      catalytic and ATP-waiting dwells. We recorded rotations and halts by means of
      microvideography in laboratory coordinates. A correlation with molecular
      coordinates was established by using an engineered pair of cysteines that, under
      oxidizing conditions, formed zero-length cross-links between the rotor and the
      stator in an orientation as found in crystals. The fixed orientation coincided
      with that of the catalytic dwell, whereas the ATP waiting dwell was displaced
      from it by +40 degrees . In crystals, the convex side of the cranked central
      shaft faces an empty nucleotide binding site, as if holding it open for arriving
      ATP. Functional studies suggest that three sites are occupied during a catalytic
      dwell. Our data imply that the convex side faces a nucleotide-occupied rather
      than an empty site. The enzyme conformation in crystals seems to differ from the
      conformation during either dwell of the active enzyme. A revision of current
      schemes of the mechanism is proposed.

PMID- 18723592
TI  - An altered mode of calcium coordination in methionine-oxidized calmodulin.
AB  - Oxidation of methionine residues in calmodulin (CaM) lowers the affinity for
      calcium and results in an inability to activate target proteins fully. To
      evaluate the structural consequences of CaM oxidation, we used infrared
      difference spectroscopy to identify oxidation-dependent effects on protein
      conformation and calcium liganding. Oxidation-induced changes include an increase
      in hydration of alpha-helices, as indicated in the downshift of the amide I' band
      of both apo-CaM and Ca(2+)-CaM, and a modification of calcium liganding by
      carboxylate side chains, reflected in antisymmetric carboxylate band shifts.
      Changes in carboxylate ligands are consistent with the model we propose: an Asp
      at position 1 of the EF-loop experiences diminished hydrogen bonding with the
      polypeptide backbone, an Asp at position 3 forms a bidentate coordination of
      calcium, and an Asp at position 5 forms a pseudobridging coordination with a
      calcium-bound water molecule. The bidentate coordination of calcium by conserved
      glutamates is unaffected by oxidation. The observed changes in calcium ligation
      are discussed in terms of the placement of methionine side chains relative to the
      calcium-binding sites, suggesting that varying sensitivities of binding sites to
      oxidation may underlie the loss of CaM function upon oxidation.

PMID- 18723593
TI  - Effect of tongue exercise on protrusive force and muscle fiber area in aging
      rats.
AB  - PURPOSE: Age-related changes in tongue function may contribute to dysphagia in
      elderly people. The authors' purpose was to investigate whether aged rats that
      have undergone tongue exercise would manifest increased protrusive tongue forces
      and increased genioglossus (GG) muscle fiber cross-sectional areas. METHOD: Forty
      eight young adult, middle-aged, and old Fischer 344/Brown Norway rats received 8
      weeks of tongue exercise. Protrusive tongue forces were measured before and after
      exercise. GG muscle fiber cross-sectional area was measured in exercised rats and
      was compared with cross-sectional areas in a no-exercise control group. RESULTS:
      A significant increase in maximum tongue force was found following exercise in
      all age groups. In addition, a trend for increased GG muscle fiber cross
      sectional area and a significant increase in variability of GG muscle fiber cross
      sectional area was identified postexercise. CONCLUSION: The findings of this
      study have implications for treatment of elderly persons with dysphagia using
      tongue exercise programs. Specifically, increases in tongue force that occur
      following 8 weeks of progressive resistance tongue exercise may be accompanied by
      alterations in tongue muscle fiber morphology. These changes may provide greater
      strength and endurance for goal-oriented actions associated with the
      oropharyngeal swallow and should be investigated in future research.

PMID- 18723595
TI  - Predictors of print knowledge in children with specific language impairment:
      experiential and developmental factors.
AB  - PURPOSE: Many children with specific language impairment (SLI) demonstrate delays
      in print knowledge, yet the reasons for these delays are not well understood. The
      present study investigates the degree to which developmental risk factors and
      home literacy experiences predict the print knowledge of children with SLI.
      METHOD: Direct child measures, maternal reports, and observations from 41 mothers
      and their preschool-aged children with SLI assessed child language and
      attentional difficulties, family socioeconomic status, the frequency and quality
      of home literacy, and children's print knowledge. RESULTS: Hierarchical multiple
      regression analyses revealed that individual differences in children's oral
      language abilities did not explain individual variability in print knowledge. The
      quality of home literacy was the only significant predictor of print knowledge,
      but its influence was moderated by children's attentional difficulties.
      CONCLUSIONS: Findings reveal that language difficulty is not an adequate
      explanation for the print knowledge delays of children with SLI and suggest that
      literacy experiences may play an important role in the print knowledge attainment
      of children with SLI. The quality of home literacy appears to foster print
      knowledge by compensating for attentional difficulties in children with SLI but
      is not sufficient to promote print knowledge in children with SLI without
      attentional difficulties.

PMID- 18723596
TI  - Accuracy assessment for AG500, electromagnetic articulograph.
AB  - PURPOSE: The goal of this article was to evaluate the accuracy and reliability of
      the AG500 (Carstens Medizinelectronik, Lenglern, Germany), an electromagnetic
      device developed recently to register articulatory movements in three dimensions.
      This technology seems to have unprecedented capabilities to provide rich
      information about time-varying positions of articulators. However, strengths and
      weaknesses of the system need to be better understood before the device is used
      for speech research. METHOD: Evaluations of the sensor positions over time were
      obtained during (a) movements of the calibration device, (b) manual movements of
      sensors in a cartridge within the recording field of the cube, and (c) various
      speech tasks. RESULTS: Results showed a median error to be under 0.5 mm across
      different types of recordings. The maximum error often ranged between 1 and 2 mm.
      The magnitude of error depended somewhat on the task but largely on the location
      of the sensors within the recording region of the cube. CONCLUSION: The
      performance of the system was judged as adequate for speech movement acquisition,
      provided that specific steps are taken for minimizing error during recording and
      for validating the quality of recorded data.

PMID- 18723597
TI  - The use of tense and agreement by Hungarian-speaking children with language
      impairment.
AB  - PURPOSE: Hungarian is a null-subject language with both agglutinating and
      fusional elements in its verb inflection system, and agreement between the verb
      and object as well as between the verb and subject. These characteristics make
      this language a good test case for alternative accounts of the grammatical
      deficits of children with language impairment (LI). METHOD: Twenty-five children
      with LI and 25 younger children serving as vocabulary controls (VC) repeated
      sentences whose verb inflections were masked by a cough. The verb inflections
      marked distinctions according to tense, person, number, and definiteness of the
      object. RESULTS: The children with LI were significantly less accurate than the
      VC children but generally showed the same performance profile across the
      inflection types. For both groups of children, the frequency of occurrence of the
      inflection in the language was a significant predictor of accuracy level. The two
      groups of children were also similar in their pattern of errors. Inflections
      produced in place of the correct inflection usually differed from the correct
      form on a single dimension (e.g., tense or definiteness), though no single
      dimension was consistently problematic. CONCLUSIONS: Accounts that assume
      problems specific to agreement do not provide an explanation for the observed
      pattern of findings. The findings are generally compatible with accounts that
      assume processing limitations in children with LI, such as the morphological
      richness account. One nonmorphosyntactic factor (the retention of sequences of
      sounds) appeared to be functionally related to inflection accuracy and may prove
      to be important in a language with numerous inflections such as Hungarian.

PMID- 18723598
TI  - Age 17 language and reading outcomes in late-talking toddlers: support for a
      dimensional perspective on language delay.
AB  - PURPOSE: This study examined whether late talkers identified at 24-31 months
      continued to have weaker language and reading skills at 17 years of age than
      typically developing peers. METHOD: Language and reading outcomes at 17 years of
      age were examined in 26 children identified as late talkers with normal nonverbal
      ability and normal receptive language at intake and in 23 typically developing
      children matched at intake on age, socioeconomic status (SES), and nonverbal
      ability. RESULTS: Although late talkers performed in the average range on all
      language and reading tasks at 17 years of age, they obtained significantly lower
      Vocabulary/Grammar and Verbal Memory factor scores than SES-matched peers. The
      age 17 Vocabulary/Grammar factor had large correlations with the age 17 Verbal
      Memory and Reading/Writing factors. The age 17 Vocabulary/Grammar and
      Reading/Writing factors were strongly predicted by comparable factors at 13 years
      of age. Age 2 Language Development Survey (L. Rescorla, 1989) vocabulary score
      explained 17% of the variance in the age 17 Vocabulary/Grammar and Verbal Memory
      factors. CONCLUSIONS: Results suggest that slow language development at 24-31
      months is associated with a weakness in language-related skills into adolescence
      relative to skills manifested by typically developing peers--findings that are
      consistent with a dimensional perspective on language delay.

PMID- 18723599
TI  - Lung volume during swallowing: single bolus swallows in healthy young adults.
AB  - PURPOSE: This study examined the relationship between swallowing and lung volume
      initiation in healthy adults during single swallows of boluses differing in
      volume and consistency. Differences in lung volume according to respiratory phase
      surrounding the swallow were also assessed. METHOD: Nine men and 11 women between
      the ages of 19 and 28 years served as study participants. Lung volume and
      respiratory phase data were recorded as each participant completed 5 trials each
      of 10-mL and 20-mL water boluses by cup, and thin and thick paste boluses by
      spoon, presented in randomized order. RESULTS: Significant differences in lung
      volume at swallow initiation were found based on bolus consistency but not on
      bolus volume. No differences were found for lung volume initiation based on the
      respiratory phase surrounding the swallow or for the respiratory pattern based on
      bolus volume or consistency. CONCLUSION: Findings of this study extend the
      existing knowledge base regarding the interaction of the swallow and respiratory
      systems by identifying targeted lung volumes at swallow initiation. In addition
      to other swallow-related biomechanical events and respiratory phase relationships
      surrounding a swallow, the lung volume at swallow initiation may be an important
      consideration when investigating swallow physiology and physiopathy.

PMID- 18723600
TI  - Phonotactic probabilities at the onset of language development: speech production
      and word position.
AB  - PURPOSE: To examine the role of phonotactic probabilities at the onset of
      language development, in a new language (Dutch), while controlling for word
      position. METHOD: Using a nonword imitation task, 64 Dutch-learning children (age
      2;2-2;8 [years;months]) were tested on how they imitated segments in low- and
      high-phonotactic probability environments, in word-initial and word-final
      position. The relationship between phonological representations and vocabulary
      development was examined by comparing children's performance with their receptive
      and expressive vocabularies. RESULTS: Segments in high-phonotactic probability
      environments were at an advantage in production, in both word-initial and word
      final position. Significant correlations were found between vocabulary size and
      children's mean segment repetition accuracy for word-initial position, but not in
      word-final position. CONCLUSION: The results indicate that phonological
      representations are mediated not only by children's developing vocabularies but
      also by the structure of children's emerging lexicons.

PMID- 18723601
TI  - Complex sentence comprehension and working memory in children with specific
      language impairment.
AB  - PURPOSE: This study investigated the association of 2 mechanisms of working
      memory (phonological short-term memory [PSTM], attentional resource
      capacity/allocation) with the sentence comprehension of school-age children with
      specific language impairment (SLI) and 2 groups of control children. METHOD:
      Twenty-four children with SLI, 18 age-matched (CA) children, and 16 language- and
      memory-matched (LMM) children completed a nonword repetition task (PSTM), the
      competing language processing task (CLPT; resource capacity/allocation), and a
      sentence comprehension task comprising complex and simple sentences. RESULTS: (1)
      The SLI group performed worse than the CA group on each memory task; (2) all 3
      groups showed comparable simple sentence comprehension, but for complex
      sentences, the SLI and LMM groups performed worse than the CA group; (3) for the
      SLI group, (a) CLPT correlated with complex sentence comprehension, and (b)
      nonword repetition correlated with simple sentence comprehension; (4) for CA
      children, neither memory variable correlated with either sentence type; and (5)
      for LMM children, only CLPT correlated with complex sentences. CONCLUSIONS:
      Comprehension of both complex and simple grammar by school-age children with SLI
      is a mentally demanding activity, requiring significant working memory resources.

PMID- 18723602
TI  - Validity of eye movement methods and indices for capturing semantic (associative)
      priming effects.
AB  - PURPOSE: The purpose of this investigation was to evaluate the usefulness of eye
      movement methods and indices as a tool for studying priming effects by verifying
      whether eye movement indices capture semantic (associative) priming effects in a
      visual cross-format (written word to semantically related picture) priming
      paradigm. METHOD: In the stimuli development phase, words semantically associated
      to an array of pictures were generated based on 100 adults' association data for
      each picture. A total of 40 additional adult participants with normal language
      engaged in an eye movement experiment using the word-picture associations
      developed previously. The design consisted of each prime preceding a display
      showing 1 high-association (target) and 2 low-association (nontarget) images.
      Fixation durations, locations, and latencies were measured. RESULTS: Images
      semantically related to the prime showed greater fixation durations and shorter
      latencies compared to nontargets. Eye movement and traditional reaction time
      measures were found to correlate for some of the experimental conditions.
      CONCLUSIONS: Results showed that free-viewing eye movement measures, in which
      participants are not instructed to look at anything in particular, hold promise
      as valid indicators of priming effects. Further research in this area will help
      to advance language-processing theories in individuals with and without language
      impairment.

PMID- 18723603
TI  - C-terminal signals regulate targeting of glycosylphosphatidylinositol-anchored
      proteins to the cell wall or plasma membrane in Candida albicans.
AB  - Fungal glycosylphosphatidylinositol (GPI)-anchored proteins localize to the
      plasma membrane (PM), cell wall (CW), or both. To study signals that regulate PM
      versus CW targeting in Candida albicans, we (i) fused the N and/or C termini of
      the GPI CW protein Hwp1p and the GPI PM protein Ecm331p to green fluorescent
      protein (GFP) and (ii) expressed and localized the resulting fusions. Forty-seven
      amino acids from the C terminus of Hwp1p were sufficient to target GFP to the CW,
      and 66 amino acids from the C terminus of Ecm331p were sufficient to target GFP
      to the PM. Truncation and mutagenesis studies showed that G390 was the omega
      cleavage site in Ecm331p. Domain exchange and mutagenesis studies showed that (i)
      the 5 amino acids immediately N-terminal to the omega sites (the omega - 5 to
      omega - 1 amino acids) played key roles in targeting to the PM or CW; (ii) KK and
      FE residues at positions omega - 1 and omega - 2, respectively, targeted to the
      PM and CW; and (iii) a loss of I at position omega - 5 increased PM retention.
      Small fluorescent reporters can be used to study the peptide signals that
      regulate PM versus CW targeting of GPI proteins and may be useful for identifying
      proteins that interact with key targeting signals.

PMID- 18723604
TI  - Copper distributed by Atx1 is available to copper amine oxidase 1 in
      Schizosaccharomyces pombe.
AB  - Copper amine oxidases (CAOs) have been proposed to be involved in the metabolism
      of xenobiotic and biogenic amines. The requirement for copper is absolute for
      their activity. In the fission yeast Schizosaccharomyces pombe, cao1(+) and
      cao2(+) genes are predicted to encode members of the CAO family. While both genes
      are expressed in wild-type cells, we determined that the expression of only
      cao1(+) but not cao2(+) results in the production of an active enzyme. Site
      directed mutagenesis identified three histidine residues within the C-terminal
      region of Cao1 that are necessary for amine oxidase activity. By use of a cao1(+)
      GFP allele that retained wild-type function, Cao1-GFP was localized in the
      cytosol (GFP is green fluorescent protein). Under copper-limiting conditions,
      disruption of ctr4(+), ctr5(+), and cuf1(+) produced a defect in amine oxidase
      activity, indicating that a functionally active Cao1 requires Ctr4/5-mediated
      copper transport and the transcription factor Cuf1. Likewise, atx1 null cells
      exhibited substantially decreased levels of amine oxidase activity. In contrast,
      deletion of ccc2, cox17, and pccs had no significant effect on Cao1 activity.
      Residual amine oxidase activity in cells lacking atx1(+) can be restored to
      normal levels by returning an atx1(+) allele, underscoring the critical
      importance of the presence of Atx1 in cells. Using two-hybrid analysis, we
      demonstrated that Cao1 physically interacts with Atx1 and that this association
      is comparable to that of Atx1 with the N-terminal region of Ccc2. Collectively,
      these results describe the first example of the ability of Atx1 to act as a
      copper carrier for a molecule other than Ccc2 and its critical role in delivering
      copper to Cao1.

PMID- 18723605
TI  - Assembly of the Trypanosoma brucei 60S ribosomal subunit nuclear export complex
      requires trypanosome-specific proteins P34 and P37.
AB  - We previously identified two Trypanosoma brucei RNA binding proteins, P34 and
      P37, and determined that they are essential for proper ribosomal assembly in this
      organism. Loss of these proteins via RNA interference is lethal and causes a
      decrease in both 5S rRNA levels and formation of 80S ribosomes, concomitant with
      a decrease in total cellular protein synthesis. These data suggest that these
      proteins are involved at some point in the ribosomal biogenesis pathway. In the
      current study, we have performed subcellular fractionation in conjunction with
      immune capture experiments specific for 60S ribosomal proteins and accessory
      factors in order to determine when and where P34 and P37 are involved in the
      ribosomal biogenesis pathway. These studies demonstrate that P34 and P37
      associate with the 60S ribosomal subunit at the stage of the nucleolar 90S
      particle and remain associated subsequent to nuclear export. In addition, P34 and
      P37 associate with conserved 60S ribosomal subunit nuclear export factors
      exportin 1 and Nmd3, suggesting that they are components of the 60S ribosomal
      subunit nuclear export complex in T. brucei. Most significantly, the pre-60S
      complex does not associate with exportin 1 or Nmd3 in the absence of P34 and P37.
      These results demonstrate that, although T. brucei 60S ribosomal subunits utilize
      a nuclear export complex similar to that described for other organisms,
      trypanosome-specific factors are essential to the process.

PMID- 18723606
TI  - Transitions in sexuality: recapitulation of an ancestral tri- and tetrapolar
      mating system in Cryptococcus neoformans.
AB  - Sex is orchestrated by the mating-type locus (MAT) in fungi and by sex
      chromosomes in plants and animals. In fungi, two patterns of sexuality occur:
      bipolar with a single, typically biallelic sex determinant that promotes
      inbreeding, and tetrapolar with two unlinked, often multiallelic sex determinants
      that restrict inbreeding. Multiallelism in either bipolar or tetrapolar mating
      systems promotes outcrossing. Cryptococcus neoformans is a pathogenic bipolar
      yeast with two unusually large MAT alleles (a/alpha) spanning >100 kb,
      approximately 100-fold larger than many other fungal MAT loci. Based on
      comparative genomic analysis, this unusual MAT locus is hypothesized to have
      evolved from an ancestral tetrapolar system. In this model, the unlinked
      homeodomain (HD) transcription factor and pheromone/receptor tetrapolar loci
      acquired additional sex-related genes and then fused via chromosomal
      translocation, forming an intermediate transitional mating system (which we term
      tripolar), which then underwent recombination and gene conversion to fashion the
      extant bipolar MAT alleles. To experimentally validate this model, C. neoformans
      was engineered to have a tetrapolar mating system by relocating the MAT SXI1alpha
      and SXI2a HD genes to an unlinked genomic locale. Genetic and molecular analyses
      revealed that this modified organism could complete a tetrapolar sexual cycle.
      Analysis of progeny generated from bipolar, tripolar, and tetrapolar crosses
      provides direct experimental evidence that the tripolar state confers decreased
      fertility and therefore may represent an unstable evolutionary intermediate.
      These findings illustrate how transitions between outcrossing and inbreeding
      preference occur by involving sex determinant linkage and collapse from
      multiallelic to biallelic sex determination, providing insights into both fungal
      sex evolution and early steps in sex chromosome evolution.

PMID- 18723607
TI  - TOR1 and TOR2 have distinct locations in live cells.
AB  - TOR is a structurally and functionally conserved Ser/Thr kinase found in two
      multiprotein complexes that regulate many cellular processes to control cell
      growth. Although extensively studied, the localization of TOR is still ambiguous,
      possibly because endogenous TOR in live cells has not been examined. Here, we
      examined the localization of green fluorescent protein (GFP) tagged, endogenous
      TOR1 and TOR2 in live S. cerevisiae cells. A DNA cassette encoding three copies
      of green fluorescent protein (3XGFP) was inserted in the TOR1 gene (at codon
      D330) or the TOR2 gene (at codon N321). The TORs were tagged internally because
      TOR1 or TOR2 tagged at the N or C terminus was not functional. The TOR1(D330
      3XGFP) strain was not hypersensitive to rapamycin, was not cold sensitive, and
      was not resistant to manganese toxicity caused by the loss of Pmr1, all
      indications that TOR1-3XGFP was expressed and functional. TOR2-3XGFP was
      functional, as TOR2 is an essential gene and TOR2(N321-3XGFP) haploid cells were
      viable. Thus, TOR1 and TOR2 retain function after the insertion of 748 amino
      acids in a variable region of their noncatalytic domain. The localization
      patterns of TOR1-3XGFP and TOR2-3XGFP were documented by imaging of live cells.
      TOR1-3XGFP was diffusely cytoplasmic and concentrated near the vacuolar membrane.
      The TOR2-3XGFP signal was cytoplasmic but predominately in dots at the plasma
      membrane. Thus, TOR1 and TOR2 have distinct localization patterns, consistent
      with the regulation of cellular processes as part of two different complexes.

PMID- 18723608
TI  - Triple genetic identities for the complete hydatidiform mole, placenta and co
      existing fetus after transfer of a single in vitro fertilized oocyte: case report
      and possible mechanisms.
AB  - We found different genotypes for the complete hydatidiform mole (CHM), placenta
      and co-existing fetus derived from a single in vitro fertilized human oocyte by
      the analysis of short tandem repeat (STR) DNA markers. The molar tissue was found
      to be heterozygously androgenetic. The fetus and placenta contained identical
      maternal, but different paternal genomes. Two models were proposed to account for
      the identification of triple genetic identities in a single fertilized oocyte. In
      the first model, the oocyte was fertilized by a diploid sperm, resulting in
      diandric triploidy. Premature cytokinesis resulted in early splitting of a
      cytoplasmic fragment with one copy of the replicated sperm chromosome, which
      developed into a heterozygous CHM. The bipolar spindle in syngamy pulled the
      other copy of sperm chromosomes and replicated oocyte chromosomes to form two
      blastomeres, which develop into the fetus and placenta, respectively. In the
      second model, the oocyte was fertilized by two haploid sperms, followed by
      tripolar spindle formation. Whatever is the mechanism, this case provides direct
      evidence that CHM can be derived from an oocyte containing an intact maternal
      genome.

PMID- 18723609
TI  - Long-term observation of 64 patients with roentgenographically occult lung cancer
      treated with external irradiation and intraluminal irradiation using low-dose
      rate iridium.
AB  - OBJECTIVE: Therapeutic results of intraluminal irradiation were analyzed in 64
      patients with roentgenographically occult lung cancer (ROLC). METHODS: The
      subjects were 64 patients who underwent intraluminal irradiation between 1987 and
      2003. Radiotherapy was performed by combining external irradiation with
      intraluminal irradiation using low-dose-rate iridium (four 370-MBq wires) through
      a catheter with a spacer. The doses of radiation were 0-70 Gy (median value 46
      Gy) by external irradiation and 10-60 Gy (median value 29.3 Gy) by intraluminal
      irradiation. RESULTS: The therapeutic effect was CR in 63 patients and PR in 1
      patient, and local recurrence was observed in a PR case and in seven of the 63
      patients who showed CR. The 5-year overall and relapse-free survival rates were
      56 (95% CI, 43-69%) and 55% (95% CI, 43-68%), respectively. Fatal pulmonary
      hemorrhage was observed in one case. CONCLUSIONS: Considering the facts that ROLC
      often occurs as multiple cancers and that many patients with ROLC have reduced
      lung function, radiation therapy by a combination of intraluminal and external
      irradiation may replace surgery as the first choice for the treatment of this
      disease.

PMID- 18723610
TI  - Stabilization of the pertussis toxin secretion apparatus by the C terminus of
      PtlD.
AB  - Pertussis toxin (PT) is secreted from Bordetella pertussis by a type IV secretion
      system, known as the Ptl transporter, that comprises nine different proteins,
      PtlA to PtlI. In this study, we found that PtlD is required for the stability of
      three Ptl proteins, PtlE, PtlF, and PtlH. A region limited to the C-terminal 72
      amino acids of PtlD (amino acids 392 to 463) was sufficient for maintaining the
      stability of PtlE, PtlF, and PtlH, although this region was not sufficient to
      support secretion of the toxin. Further analysis demonstrated that a stretch of
      10 amino acids at the C-terminal end of PtlD (amino acids 425 to 434) contributes
      to transporter stability.

PMID- 18723611
TI  - The carboxyl-terminal domain of TraR, a Streptomyces HutC family repressor,
      functions in oligomerization.
AB  - Efficient conjugative transfer of the Streptomyces plasmid pSN22 is accomplished
      by regulated expression of the tra operon genes, traA, traB, and spdB. The TraR
      protein is the central transcriptional repressor regulating the expression of the
      tra operon and itself and is classified as a member of the HutC subfamily in the
      helix-turn-helix (HTH) GntR protein family. Sequence information predicts that
      the N-terminal domain (NTD) of TraR, containing an HTH motif, functions in
      binding of DNA to the cis element; however, the function of the C-terminal region
      remains obscure, like that for many other GntR family proteins. Here we
      demonstrate the domain structure of the TraR protein and explain the role of the
      C-terminal domain (CTD). The TraR protein can be divided into two structural
      domains, the NTD of M1 to R95 and the CTD of Y96 to E246, revealed by limited
      proteolysis. Domain expression experiments revealed that both domains retained
      their function. An in vitro pull-down assay using recombinant TraR proteins
      revealed that TraR oligomerization depended on the CTD. A bacterial two-hybrid
      system interaction assay revealed that the minimum region necessary for this
      binding is R95 to P151. A mutant TraR protein in which Leu121 was replaced by His
      exhibited a loss of both oligomerization ability and repressor function. An in
      vitro cross-linking assay revealed preferential tetramer formation by TraR and
      the minimum CTD. These results indicate that the C-terminal R95-to-P151 region of
      TraR functions to form an oligomer, preferentially a tetramer, that is essential
      for the repressor function of TraR.

PMID- 18723612
TI  - Functional studies of multiple thioredoxins from Mycobacterium tuberculosis.
AB  - Cytoplasmic protein reduction via generalized thiol/disulfide exchange reactions
      and maintenance of cellular redox homeostasis is mediated by the thioredoxin
      superfamily of proteins. Here, we describe the characterization of the
      thioredoxin system from Mycobacterium tuberculosis, whose genome bears the
      potential to encode three putative thioredoxins from the open reading frames
      designated trxAMtb, trxBMtb, and trxCMtb. We show that all three thioredoxins,
      overproduced in Escherichia coli, are able to reduce insulin, a model substrate,
      in the presence of dithiothreitol. However, we observe that thioredoxin reductase
      is not capable of reducing TrxAMtb in an NADPH-dependent manner, indicating that
      only TrxBMtb and TrxCMtb are the biologically active disulfide reductases. The
      absence of detectable mRNA transcripts of trxAMtb observed when M. tuberculosis
      strain H37Rv was cultivated under different growth conditions suggests that
      trxAMtb expression may be cryptic. The measured redox potentials of TrxBMtb and
      TrxCMtb (-262+/-2 mV and -269+/-2 mV, respectively) render these proteins
      somewhat more oxidizing than E. coli thioredoxin 1 (TrxA). In E. coli strains
      lacking components of cytoplasmic protein reduction pathways, heterologous
      expression of the mycobacterial thioredoxins was able to effectively substitute
      for their function.

PMID- 18723613
TI  - ESAT-6-like protein secretion in Bacillus anthracis.
AB  - Proteins of the WXG100 family represent the prototypical substrates of bacterial
      type VII secretion systems that typically encompass 100 residues, lack canonical
      signal peptides, and form helix-turn-helix hairpin structures with WXG positioned
      in the turn element. Bacillus anthracis encodes six WXG100 proteins, herein
      referred to as EsxB, EsxL, EsxP, EsxQ, EsxV, and EsxW. With the exception of
      EsxB, B. anthracis proteins harbor C-terminal extensions that are appended to
      canonical WXG domains. When cultured in liquid broth, B. anthracis secretes two
      substrates, EsxB and EsxW, into the extracellular environment. EsxB is required
      for the stability and secretion of EsxW; however, EsxW is dispensable for EsxB
      secretion. In agreement with the hypothesis that EsxB binding to substrates
      promotes recognition and secretion by the type VII pathway, EsxB is reported to
      interact with EsxB and EsxW. Unlike deletions in mycobacterial EsxB, deletion of
      five N- or C-terminal residues does not affect the ability of mutant B. anthracis
      EsxB to travel the type VII pathway and initiate secretion of EsxW. Translational
      fusion of ubiquitin to the N or C terminus of EsxB also had no effect, while
      ubiquitin insertion into the center turn abrogated secretion. Anthrax-infected
      guinea pigs mounted humoral immune responses to EsxB, EsxP, and EsxW, which
      suggests that B. anthracis activates the type VII secretion pathway during
      infection.

PMID- 18723614
TI  - Use of CDP-glycerol as an alternate acceptor for the teichoic acid polymerase
      reveals that membrane association regulates polymer length.
AB  - The study of bacterial extracellular polysaccharide biosynthesis is hampered by
      the fact that these molecules are synthesized on membrane-resident carrier
      lipids. To get around this problem, a practical solution has been to synthesize
      soluble lipid analogs and study the biosynthetic enzymes using a soluble system.
      This has been done for the Bacillus subtilis teichoic acid polymerase, TagF,
      although several aspects of catalysis were inconsistent with the results obtained
      with reconstituted membrane systems or physiological observations. In this work
      we explored the acceptor substrate promiscuity and polymer length disregulation
      that appear to be characteristic of TagF activity away from biological membranes.
      Using isotope labeling, steady-state kinetics, and chemical lability studies, we
      demonstrated that the enzyme can synthesize poly(glycerol phosphate) teichoic
      acid using the elongation substrate CDP-glycerol as an acceptor. This suggests
      that substrate specificity is relaxed in the region distal to the glycerol
      phosphate moiety in the acceptor molecule under these conditions. Polymer
      synthesis proceeded at a rate (27 min(-1)) comparable to that in the
      reconstituted membrane system after a distinct lag period which likely
      represented slower initiation on the unnatural CDP-glycerol acceptor. We
      confirmed that polymer length became disregulated in the soluble system as the
      polymers synthesized on CDP-glycerol acceptors were much larger than the polymers
      synthesized on the membrane or previously found attached to bacterial cell walls.
      Finally, polymer synthesis on protease-treated membranes suggested that proper
      length regulation is retained in the absence of accessory proteins and provided
      evidence that such regulation is conferred through proper association of the
      polymerase with the membrane.

PMID- 18723615
TI  - Genome sequence of the fish pathogen Renibacterium salmoninarum suggests
      reductive evolution away from an environmental Arthrobacter ancestor.
AB  - Renibacterium salmoninarum is the causative agent of bacterial kidney disease and
      a significant threat to healthy and sustainable production of salmonid fish
      worldwide. This pathogen is difficult to culture in vitro, genetic manipulation
      is challenging, and current therapies and preventative strategies are only
      marginally effective in preventing disease. The complete genome of R.
      salmoninarum ATCC 33209 was sequenced and shown to be a 3,155,250-bp circular
      chromosome that is predicted to contain 3,507 open-reading frames (ORFs). A total
      of 80 copies of three different insertion sequence elements are interspersed
      throughout the genome. Approximately 21% of the predicted ORFs have been
      inactivated via frameshifts, point mutations, insertion sequences, and putative
      deletions. The R. salmoninarum genome has extended regions of synteny to the
      Arthrobacter sp. strain FB24 and Arthrobacter aurescens TC1 genomes, but it is
      approximately 1.9 Mb smaller than both Arthrobacter genomes and has a lower G+C
      content, suggesting that significant genome reduction has occurred since
      divergence from the last common ancestor. A limited set of putative virulence
      factors appear to have been acquired via horizontal transmission after divergence
      of the species; these factors include capsular polysaccharides, heme
      sequestration molecules, and the major secreted cell surface antigen p57 (also
      known as major soluble antigen). Examination of the genome revealed a number of
      ORFs homologous to antibiotic resistance genes, including genes encoding beta
      lactamases, efflux proteins, macrolide glycosyltransferases, and rRNA
      methyltransferases. The genome sequence provides new insights into R.
      salmoninarum evolution and may facilitate identification of chemotherapeutic
      targets and vaccine candidates that can be used for prevention and treatment of
      infections in cultured salmonids.

PMID- 18723616
TI  - The origins of 168, W23, and other Bacillus subtilis legacy strains.
AB  - Bacillus subtilis is both a model organism for basic research and an industrial
      workhorse, yet there are major gaps in our understanding of the genomic heritage
      and provenance of many widely used strains. We analyzed 17 legacy strains dating
      to the early years of B. subtilis genetics. For three--NCIB 3610T, PY79, and SMY-
      we performed comparative genome sequencing. For the remainder, we used
      conventional sequencing to sample genomic regions expected to show sequence
      heterogeneity. Sequence comparisons showed that 168, its siblings (122, 160, and
      166), and the type strains NCIB 3610 and ATCC 6051 are highly similar and are
      likely descendants of the original Marburg strain, although the 168 lineage shows
      genetic evidence of early domestication. Strains 23, W23, and W23SR are identical
      in sequence to each other but only 94.6% identical to the Marburg group in the
      sequenced regions. Strain 23, the probable W23 parent, likely arose from a
      contaminant in the mutagenesis experiments that produced 168. The remaining
      strains are all genomic hybrids, showing one or more "W23 islands" in a 168
      genomic backbone. Each traces its origin to transformations of 168 derivatives
      with DNA from 23 or W23. The common prototrophic lab strain PY79 possesses
      substantial W23 islands at its trp and sac loci, along with large deletions that
      have reduced its genome 4.3%. SMY, reputed to be the parent of 168, is actually a
      168-W23 hybrid that likely shares a recent ancestor with PY79. These data provide
      greater insight into the genomic history of these B. subtilis legacy strains.

PMID- 18723617
TI  - Suppressor analysis of the MotB(D33E) mutation to probe bacterial flagellar motor
      dynamics coupled with proton translocation.
AB  - MotA and MotB form the stator of the proton-driven bacterial flagellar motor,
      which conducts protons and couples proton flow with motor rotation. Asp-33 of
      Salmonella enterica serovar Typhimurium MotB, which is a putative proton-binding
      site, is critical for torque generation. However, the mechanism of energy
      coupling remains unknown. Here, we carried out genetic and motility analysis of a
      slowly motile motB(D33E) mutant and its pseudorevertants. We first confirmed that
      the poor motility of the motB(D33E) mutant is due to neither protein instability,
      mislocalization, nor impaired interaction with MotA. We isolated 17
      pseudorevertants and identified the suppressor mutations in the transmembrane
      helices TM2 and TM3 of MotA and in TM and the periplasmic domain of MotB. The
      stall torque produced by the motB(D33E) mutant motor was about half of the wild
      type level, while those for the pseudorevertants were recovered nearly to the
      wild-type levels. However, the high-speed rotations of the motors under low-load
      conditions were still significantly impaired, suggesting that the rate of proton
      translocation is still severely limited at high speed. These results suggest that
      the second-site mutations recover a torque generation step involving stator-rotor
      interactions coupled with protonation/deprotonation of Glu-33 but not maximum
      proton conductivity.

PMID- 18723618
TI  - Purification and characterization of the bacterial UDP-GlcNAc:undecaprenyl
      phosphate GlcNAc-1-phosphate transferase WecA.
AB  - To date, the structural and functional characterization of proteins belonging to
      the polyprenyl-phosphate N-acetylhexosamine-1-phosphate transferase superfamily
      has been relentlessly held back by problems encountered with their overexpression
      and purification. In the present work and for the first time, the integral
      membrane protein WecA that catalyzes the transfer of the GlcNAc-1-phosphate
      moiety from UDP-GlcNAc onto the carrier lipid undecaprenyl phosphate, yielding
      undecaprenyl-pyrophosphoryl-GlcNAc, the lipid intermediate involved in the
      synthesis of various bacterial cell envelope components, was overproduced and
      purified to near homogeneity in milligram quantities. An enzymatic assay was
      developed, and the kinetic parameters of WecA as well as the effects of pH,
      salts, cations, detergents, and temperature on the enzyme activity were
      determined. A minimal length of 35 carbons was required for the lipid substrate,
      and tunicamycin was shown to inhibit the enzyme at submicromolar concentrations.

PMID- 18723619
TI  - The Anabaena sp. strain PCC 7120 gene all2874 encodes a diguanylate cyclase and
      is required for normal heterocyst development under high-light growth conditions.
AB  - The genome of the heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120
      harbors 14 genes containing a GGDEF diguanylate cyclase domain. We found that
      inactivation of one of these genes, all2874, caused abnormal heterocyst
      development. The all2874 mutant showed a pronounced reduction in heterocyst
      frequency during diazotrophic growth and reduced vegetative cell size compared to
      the wild type. The severity of the mutant phenotype varied with light intensity;
      at high light intensity, the mutant phenotype was accentuated, whereas at low
      light intensity the phenotype was similar to wild type. Under high-light growth
      conditions, the initial heterocyst frequency and pattern for the all2874 mutant
      were normal, but within 4 days following nitrogen step-down, many intervals
      between heterocysts increased to as many as 200 vegetative cells, whereas in the
      wild type the intervals were less than 25 vegetative cells. Filaments containing
      these unusually long vegetative cell intervals between heterocysts also contained
      intervals of normal length. An all2874 mutant strain carrying a P(patS)-gfp
      transcriptional reporter fusion failed to show normal upregulation of the
      reporter, which indicates that the decrease in heterocyst frequency is due to an
      early block in differentiation before induction of the patS gene, which in the
      wild type takes place 8 h after nitrogen step-down. Genetic epistasis experiments
      suggest that All2874 acts upstream of the master regulator HetR in
      differentiating cells. We also showed that purified All2874 functions as a
      diguanylate cyclase in vitro. We hypothesize that All2874 is required for the
      normal regulation of heterocyst frequency under high-light growth conditions.

PMID- 18723620
TI  - Characterization of spores of Bacillus subtilis that lack most coat layers.
AB  - Spores of Bacillus subtilis have a thick outer layer of relatively insoluble
      protein called the coat, which protects spores against a number of treatments and
      may also play roles in spore germination. However, elucidation of precise roles
      of the coat in spore properties has been hampered by the inability to prepare
      spores lacking all or most coat material. In this work, we show that spores of a
      strain with mutations in both the cotE and gerE genes, which encode proteins
      involved in coat assembly and expression of genes encoding coat proteins,
      respectively, lack most extractable coat protein as seen by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, as well as the great majority of the
      coat as seen by atomic force microscopy. However, the cotE gerE spores did retain
      a thin layer of insoluble coat material that was most easily seen by microscopy
      following digestion of these spores with lysozyme. These severely coat-deficient
      spores germinated relatively normally with nutrients and even better with
      dodecylamine but not with a 1:1 chelate of Ca(2+) and dipicolinic acid. These
      spores were also quite resistant to wet heat, to mechanical disruption, and to
      treatment with detergents at an elevated temperature and pH but were exquisitely
      sensitive to killing by sodium hypochlorite. These results provide new insight
      into the role of the coat layer in spore properties.

PMID- 18723621
TI  - Sigma32-mediated negative regulation of Salmonella pathogenicity island 1
      expression.
AB  - Salmonella pathogenicity island 1 (SPI1) enables infecting salmonellae to invade
      the intestinal epithelium and induce a proinflammatory response and macrophage
      cell death. SPI1 expression is controlled by a complex cascade with several
      transcriptional regulators within the island and global regulators outside it.
      Previously, we reported that DnaK-depleted salmonellae could neither invade
      epithelial cells nor secrete SPI1-encoded proteins, suggesting that DnaK is
      involved in the expression of SPI1. Here, we found that DnaK is involved in SPI1
      expression through inhibition of sigma(32) protein, which directs the
      transcription of a group of genes in response to various global stresses.
      Overproduction of sigma(32) resulted in decreased levels of the SPI1-specific
      transcriptional regulators HilD and HilA. Further analysis demonstrated that the
      sigma(32)-mediated system negatively regulates HilD and HilA at the
      posttranslational and transcriptional levels, respectively. The executioner of
      this negative regulation was shown to be a sigma(32)-induced protein ATP
      dependent Lon protease, which specifically degrades HilD. Since HilD can activate
      hilA transcription, is at the top of the hierarchical SPI1 regulatory loop, and
      has a dominant role, the posttranslational control of HilD by Lon is critically
      important for precise expression of SPI1. Consequently, we suggest that SPI1
      expression is controlled by the feedback regulatory loop in which sigma(32)
      induces Lon to control turnover of HilD, and DnaK, which inhibits sigma(32)
      function, leading to the modulation of lon expression. This regulation in
      response to a specific combination of environmental signals would ensure that
      SPI1 expression is restricted to a few specific locations in the host.

PMID- 18723622
TI  - Functional definition and global regulation of Zur, a zinc uptake regulator in a
      Streptococcus suis serotype 2 strain causing streptococcal toxic shock syndrome.
AB  - Zinc is an essential trace element for all living organisms and plays pivotal
      roles in various cellular processes. However, an excess of zinc is extremely
      deleterious to cells. Bacteria have evolved complex machineries (such as
      efflux/influx systems) to control the concentration at levels appropriate for the
      maintenance of zinc homeostasis in cells and adaptation to the environment. The
      Zur (zinc uptake regulator) protein is one of these functional members involved
      in the precise control of zinc homeostasis. Here we identified a zur homologue
      designated 310 from Streptococcus suis serotype 2, strain 05ZYH33, a highly
      invasive isolate causing streptococcal toxic shock syndrome. Biochemical analysis
      revealed that the protein product of gene 310 exists as a dimer form and carries
      zinc ions. An isogenic gene replacement mutant of gene 310, the Delta310 mutant,
      was obtained by homologous recombination. Physiological tests demonstrated that
      the Delta310 mutant is specifically sensitive to Zn(2+), while functional
      complementation of the Delta310 mutant can restore its duration capability,
      suggesting that 310 is a functional member of the Zur family. Two-dimensional
      electrophoresis indicated that nine proteins in the Delta310 mutant are
      overexpressed in comparison with those in the wild type. DNA microarray analyses
      suggested that 121 genes in the Delta310 mutant are affected, of which 72 genes
      are upregulated and 49 are downregulated. The transcriptome of S. suis serotype 2
      with high Zn(2+) concentrations also showed 117 differentially expressed genes,
      with 71 upregulated and 46 downregulated. Surprisingly, more than 70% of the
      genes differentially expressed in the Delta310 mutant were the same as those in
      S. suis serotype 2 that were differentially expressed in response to high Zn(2+)
      concentration, consistent with the notion that 310 is involved in zinc
      homeostasis. We thus report for the first time a novel zinc-responsive regulator,
      Zur, from Streptococcus suis serotype 2.

PMID- 18723623
TI  - Chemotaxis as an emergent property of a swarm.
AB  - We have characterized and quantified a form of bacterial chemotaxis that
      manifests only as an emergent property by measuring symmetry breaking in a swarm
      of Myxococcus xanthus exposed to a two-dimensional nutrient gradient from within
      an agar substrate. M. xanthus chemotaxis requires cell-cell contact and
      coordinated motility, as individual motile cells exhibit only nonvectorial
      movement in the presence of a nutrient gradient. Genes that specifically affect
      M. xanthus chemotaxis include at least 10 of the 53 that express enhancer binding
      proteins of the NtrC-like class, an indication that this behavior is controlled
      through transcription, most likely by a complex signal transduction network.

PMID- 18723624
TI  - NorB, an efflux pump in Staphylococcus aureus strain MW2, contributes to
      bacterial fitness in abscesses.
AB  - While remaining a major problem in hospitals, Staphylococcus aureus is now
      spreading in communities. Strain MW2 (USA400 lineage) and other community
      methicillin-resistant S. aureus strains most commonly cause skin infections with
      abscess formation. Multidrug resistance (MDR) efflux pumps contribute to
      antimicrobial resistance but may also contribute to bacterial survival by removal
      of environmental toxins. In S. aureus, NorA, NorB, NorC, and Tet38 are
      chromosomally encoded efflux pumps whose overexpression can confer MDR to
      quinolones and other compounds (Nor pumps) or tetracyclines alone (Tet38), but
      the natural substrates of these pumps are not known. To determine the role of
      these efflux pumps in a natural environment in the absence of antibiotics, we
      used strain MW2 in a mouse subcutaneous abscess model and compared pump gene
      expression as determined by reverse transcription-PCR in the abscesses and in
      vitro. norB and tet38 were selectively upregulated in vivo more than 171- and 24
      fold, respectively, whereas norA and norC were downregulated. These changes were
      associated with an increase in expression of mgrA, which encodes a
      transcriptional regulator known to affect pump gene expression. In competition
      experiments using equal inocula of a norB or tet38 mutant and parent strain MW2,
      each mutant exhibited growth defects of about two- to threefold in vivo. In
      complementation experiments, a single-copy insertion of norB (but not a single
      copy insertion of tet38) in the attB site within geh restored the growth fitness
      of the norB mutant in vivo. Our findings indicate that some MDR pumps, like NorB,
      can facilitate bacterial survival when they are overexpressed in a staphylococcal
      abscess and may contribute to the relative resistance of abscesses to
      antimicrobial therapy, thus linking bacterial fitness and resistance in vivo.

PMID- 18723625
TI  - In vivo inactivation of the mycobacterial integral membrane stearoyl coenzyme A
      desaturase DesA3 by a C-terminus-specific degradation process.
AB  - DesA3 (Rv3229c) from Mycobacterium tuberculosis is a membrane-bound stearoyl
      coenzyme A Delta(9) desaturase that reacts with the oxidoreductase Rv3230c to
      produce oleic acid. This work provides evidence for a mechanism used by
      mycobacteria to regulate this essential enzyme activity. DesA3 expressed as a
      fusion with either a C-terminal His(6) or c-myc tag had consistently higher
      activity and stability than native DesA3 having the native C-terminal sequence of
      LAA, which apparently serves as a binding determinant for a mycobacterial
      protease/degradation system directed at DesA3. Fusion of only the last 12
      residues of native DesA3 to the C terminus of green fluorescent protein (GFP) was
      sufficient to make GFP unstable. Furthermore, the comparable C-terminal sequence
      from the Mycobacterium smegmatis DesA3 homolog Msmeg_1886 also conferred
      instability to the GFP fusion. Systematic examination revealed that residues with
      charged side chains, large nonpolar side chains, or no side chain at the last two
      positions were most important for stabilizing the construct, while lesser effects
      were observed at the third-from-last position. Using these rules, a combinational
      substitution of the last three residues of DesA3 showed that either DKD or LEA
      gave the best enhancement of stability for the modified GFP in M. smegmatis.
      Moreover, upon mutagenesis of LAA at the C terminus in native DesA3 to either of
      these tripeptides, the modified enzyme had enhanced catalytic activity and
      stability. Since many proteases are conserved within bacterial families, it is
      reasonable that M. tuberculosis will use a similar C-terminal degradation system
      to posttranslationally regulate the activity of DesA3 and other proteins.
      Application of these rules to the M. tuberculosis genome revealed that
      approximately 10% the proteins encoded by essential genes may be susceptible to C
      terminal proteolysis. Among these, an annotation is known for less than half,
      underscoring a general lack of understanding of proteins that have only temporal
      existence in a cell.

PMID- 18723626
TI  - Reexamination of the role of the amino terminus of SecA in promoting its
      dimerization and functional state.
AB  - The SecA nanomotor promotes protein translocation in eubacteria by binding both
      protein cargo and the protein-conducting channel and by undergoing ATP-driven
      conformation cycles that drive this process. There are conflicting reports about
      whether SecA functions as a monomer or dimer during this dynamic process. Here we
      reexamined the roles of the amino and carboxyl termini of SecA in promoting its
      dimerization and functional state by examining three secA mutants and the
      corresponding proteins: SecADelta8 lacking residues 2 to 8, SecADelta11 lacking
      residues 2 to 11, and SecADelta11/N95 lacking both residues 2 to 11 and the
      carboxyl-terminal 70 residues. We demonstrated that whether SecADelta11 or
      SecADelta11/N95 was functional for promoting cell growth depended solely on the
      vivo level of the protein, which appeared to govern residual dimerization. All
      three SecA mutant proteins were defective for promoting cell growth unless they
      were highly overproduced. Cell fractionation revealed that SecADelta11 and
      SecADelta11/N95 were proficient in membrane association, although the formation
      of integral membrane SecA was reduced. The presence of a modestly higher level of
      SecADelta11/N95 in the membrane and the ability of this protein to form dimers,
      as detected by chemical cross-linking, were consistent with the higher level of
      secA expression and better growth of the SecADelta11/N95 mutant than of the
      SecADelta11 mutant. Biochemical studies showed that SecADelta11 and
      SecADelta11/N95 had identical dimerization defects, while SecADelta8 was
      intermediate between these proteins and wild-type SecA in terms of dimer
      formation. Furthermore, both SecADelta11 and SecADelta11/N95 were equally
      defective in translocation ATPase specific activity. Our studies showed that the
      nonessential carboxyl-terminal 70 residues of SecA play no role in its
      dimerization, while increasing the truncation of the amino-terminal region of
      SecA from 8 to 11 residues results in increased defects in SecA dimerization and
      poor in vivo function unless the protein is highly overexpressed. They also
      clarified a number of conflicting previous reports and support the essential
      nature of the SecA dimer.

PMID- 18723627
TI  - Stygiolobus rod-shaped virus and the interplay of crenarchaeal rudiviruses with
      the CRISPR antiviral system.
AB  - A newly characterized archaeal rudivirus Stygiolobus rod-shaped virus (SRV),
      which infects a hyperthermophilic Stygiolobus species, was isolated from a hot
      spring in the Azores, Portugal. Its virions are rod-shaped, 702 (+/- 50) by 22
      (+/- 3) nm in size, and nonenveloped and carry three tail fibers at each
      terminus. The linear double-stranded DNA genome contains 28,096 bp and an
      inverted terminal repeat of 1,030 bp. The SRV shows morphological and genomic
      similarities to the other characterized rudiviruses Sulfolobus rod-shaped virus 1
      (SIRV1), SIRV2, and Acidianus rod-shaped virus 1, isolated from hot acidic
      springs of Iceland and Italy. The single major rudiviral structural protein is
      shown to generate long tubular structures in vitro of similar dimensions to those
      of the virion, and we estimate that the virion constitutes a single,
      superhelical, double-stranded DNA embedded into such a protein structure. Three
      additional minor conserved structural proteins are also identified. Ubiquitous
      rudiviral proteins with assigned functions include glycosyl transferases and a S
      adenosylmethionine-dependent methyltransferase, as well as a Holliday junction
      resolvase, a transcriptionally coupled helicase and nuclease implicated in DNA
      replication. Analysis of matches between known crenarchaeal chromosomal CRISPR
      spacer sequences, implicated in a viral defense system, and rudiviral genomes
      revealed that about 10% of the 3,042 unique acidothermophile spacers yield
      significant matches to rudiviral genomes, with a bias to highly conserved protein
      genes, consistent with the widespread presence of rudiviruses in hot acidophilic
      environments. We propose that the 12-bp indels which are commonly found in
      conserved rudiviral protein genes may be generated as a reaction to the presence
      of the host CRISPR defense system.

PMID- 18723628
TI  - Trade-off between iron uptake and protection against oxidative stress: deletion
      of cueO promotes uropathogenic Escherichia coli virulence in a mouse model of
      urinary tract infection.
AB  - The periplasmic multicopper oxidase (CueO) is involved in copper homeostasis and
      protection against oxidative stress. Here, we show that the deletion of cueO in
      uropathogenic Escherichia coli increases its colonization of the urinary tract
      despite its increased sensitivity to hydrogen peroxide. The cueO deletion mutant
      accumulated iron with increased efficiency compared to its parent strain; this
      may account for its advantage in the iron-limited environment of the urinary
      tract.

PMID- 18723629
TI  - SpoT regulates DnaA stability and initiation of DNA replication in carbon-starved
      Caulobacter crescentus.
AB  - Cell cycle progression and polar differentiation are temporally coordinated in
      Caulobacter crescentus. This oligotrophic bacterium divides asymmetrically to
      produce a motile swarmer cell that represses DNA replication and a sessile
      stalked cell that replicates its DNA. The initiation of DNA replication coincides
      with the proteolysis of the CtrA replication inhibitor and the accumulation of
      DnaA, the replication initiator, upon differentiation of the swarmer cell into a
      stalked cell. We analyzed the adaptive response of C. crescentus swarmer cells to
      carbon starvation and found that there was a block in both the swarmer-to-stalked
      cell polar differentiation program and the initiation of DNA replication. SpoT is
      a bifunctional synthase/hydrolase that controls the steady-state level of the
      stress-signaling nucleotide (p)ppGpp, and carbon starvation caused a SpoT
      dependent increase in (p)ppGpp concentration. Carbon starvation activates DnaA
      proteolysis (B. Gorbatyuk and G. T. Marczynski, Mol. Microbiol. 55:1233-1245,
      2005). We observed that SpoT is required for this phenomenon in swarmer cells,
      and in the absence of SpoT, carbon-starved swarmer cells inappropriately
      initiated DNA replication. Since SpoT controls (p)ppGpp abundance, we propose
      that this nucleotide relays carbon starvation signals to the cellular factors
      responsible for activating DnaA proteolysis, thereby inhibiting the initiation of
      DNA replication. SpoT, however, was not required for the carbon starvation block
      of the swarmer-to-stalked cell polar differentiation program. Thus, swarmer cells
      utilize at least two independent signaling pathways to relay carbon starvation
      signals: a SpoT-dependent pathway mediating the inhibition of DNA replication
      initiation, and a SpoT-independent pathway(s) that blocks morphological
      differentiation.

PMID- 18723630
TI  - The transcriptional factors MurR and catabolite activator protein regulate N
      acetylmuramic acid catabolism in Escherichia coli.
AB  - The MurNAc etherase MurQ of Escherichia coli is essential for the catabolism of
      the bacterial cell wall sugar N-acetylmuramic acid (MurNAc) obtained either from
      the environment or from the endogenous cell wall (i.e., recycling). High-level
      expression of murQ is required for growth on MurNAc as the sole source of carbon
      and energy, whereas constitutive low-level expression of murQ is sufficient for
      the recycling of peptidoglycan fragments continuously released from the cell wall
      during growth of the bacteria. Here we characterize for the first time the
      expression of murQ and its regulation by MurR, a member of the poorly
      characterized RpiR/AlsR family of transcriptional regulators. Deleting murR
      abolished the extensive lag phase observed for E. coli grown on MurNAc and
      enhanced murQ transcription some 20-fold. MurR forms a stable multimer (most
      likely a tetramer) and binds to two adjacent inverted repeats within an operator
      region. In this way MurR represses transcription from the murQ promoter and also
      interferes with its own transcription. MurNAc-6-phosphate, the substrate of MurQ,
      was identified as a specific inducer that weakens binding of MurR to the
      operator. Moreover, murQ transcription depends on the activation by cyclic AMP
      (cAMP)-catabolite activator protein (CAP) bound to a class I site upstream of the
      murQ promoter. murR and murQ are divergently orientated and expressed from
      nonoverlapping face-to-face (convergent) promoters, yielding transcripts that are
      complementary at their 5' ends. As a consequence of this unusual promoter
      arrangement, cAMP-CAP also affects murR transcription, presumably by acting as a
      roadblock for RNA polymerase.

PMID- 18723632
TI  - Science rebooted: what the trend toward online collaboration might mean for a
      journal like The Biological Bulletin.

PMID- 18723633
TI  - Evolutionary and structural diversification of the larval nervous system among
      marine bryozoans.
AB  - Regardless of the morphological divergence among larval forms of marine
      bryozoans, the larval nervous system and its major effector organs (musculature
      and ciliary fields) are largely molded on the basis of functional demands of
      feeding, ciliary propulsion, phototactic behaviors, and substrate exploration.
      Previously published ultrastructural information and immunohistochemical
      reconstructions presented here indicate that neuronal pathways are largely
      ipsilateral, with more complex synaptic connections localized within the nerve
      nodule. Multiciliated sensory-motor neurons diversify structurally and
      functionally on the basis of their position along the axis of swimming largely
      due to the functional demands of photoklinotaxis and substrate exploration.
      Vesiculariform, buguliform, and ascophoran coronate larvae all have patches of
      sensory neurons bordering the pyriform organ's ciliated groove (juxtapapillary
      cells and border cells) that are active during substrate selection. Despite their
      simplified form, cyclostome larvae maintain swimming and probing behaviors with
      sensory-motor systems functionally similar to those of some parenchymella and
      planula larval types. Considering the evolutionary relationships among the
      morphological grades of marine bryozoans, particular lineages within the
      gymnolaemates have independently evolved larval traits that convey a greater
      range of sensory abilities and increased propulsive capacity. The larval nervous
      system of bryozoans may be evolutionarily derived from the pretrochal region of a
      trochophore-like larval form.

PMID- 18723634
TI  - Identification of chemosensory sensilla mediating antennular flicking behavior in
      Panulirus argus, the Caribbean spiny lobster.
AB  - Crustaceans sample odorants by a rapid series of flicks of the two flagella
      composing the distal segments of each of the paired antennules. The lateral
      flagella contain aesthetasc sensilla that house unimodal chemosensory neurons.
      Nine types of nonaesthetasc setae with putative chemosensory and mechanosensory
      functions are distributed on the lateral and medial flagella. Sensory neurons in
      aesthetascs and nonaesthetasc sensilla terminate in separate regions of the
      brain, the olfactory lobe, and the lateral antennular neuropil, resulting in two
      odorant-processing pathways. Distilled water ablation of flagella and excision of
      specific setae were used to identify chemosensory sensilla mediating antennular
      flick behavior in Panulirus argus. The flick rates of sham-ablated and ablated or
      excised lobsters toward squid extract were compared. Complete attenuation of
      flick response to squid extract occurred as a result of (1) distilled water
      ablation of lateral flagella, (2) excision of aesthetascs and asymmetric
      sensilla, and (3) excision of aesthetascs. Distilled water ablation of medial
      flagella resulted in a mean flick rate 52% of that observed for sham-ablated
      lobsters toward squid extract. Flicking was unaffected by excision of asymmetric,
      guard, or companion sensilla. We propose that odorant mediation of flicking
      behavior requires both the aesthetasc and nonaesthetasc pathways.

PMID- 18723631
TI  - Toll receptor 4 Asp299Gly polymorphism and its association with preterm birth and
      premature rupture of membranes in a South American population.
AB  - Preterm birth (PTB) is a worldwide health problem and remains the leading cause
      of perinatal morbidity and mortality. Systemic and local intrauterine infections
      have been implicated in the pathogenesis of preterm labor and delivery. Common
      pathways between PTB, premature rupture of ovular membranes (PROM) and altered
      molecular routes of inflammation have been proposed. There is evidence to support
      a genetic component in these conditions. Lipopolysaccharide (LPS), a component of
      the cell wall of Gram-negative bacteria, is thought to play a key role in
      eliciting an inflammatory response. LPS is recognized by proteins of the innate
      immune system, including Toll-like receptor 4 (TLR4). Individuals from some
      European countries carrying the variant alleles resulting in an amino acid
      substitution (Asp299Gly) are at increased risk of Gram-negative infections and
      premature birth. The objective of this study was to determine if preterm newborns
      have different allele frequency of the Asp299Gly TLR4 variant from healthy term
      neonates in Uruguay. The impact of PROM was also examined. There was an increase
      in the risk for fetuses carrying the Asp299Gly substitution in TLR4 of being
      severely premature (<33 weeks) and to present PROM at the same time.

PMID- 18723635
TI  - Rhythms of locomotion expressed by Limulus polyphemus, the American horseshoe
      crab: I. Synchronization by artificial tides.
AB  - Limulus polyphemus, the American horseshoe crab, has an endogenous clock that
      drives circatidal rhythms of locomotor activity. In this study, we examined the
      ability of artificial tides to entrain the locomotor rhythms of Limulus in the
      laboratory. In experiments one and two, the activity of 16 individuals of L.
      polyphemus was monitored with activity boxes and "running wheels." When the crabs
      were exposed to artificial tides created by changes in water depth, circatidal
      rhythms were observed in animals exposed to 12.4-h "tidal" cycles of either water
      depth changes (8 of 8 animals) or inundation (7 of 8 animals). In experiment
      three, an additional 8 animals were exposed to water depth changes under cyclic
      conditions of light and dark and then monitored for 10 days with no imposed
      artificial tides. Most animals (5) clearly synchronized their activity to the
      imposed artificial tidal cycles, and 3 of these animals showed clear evidence of
      entrainment after the artificial tides were terminated. Overall, these results
      demonstrate that the endogenous tidal clock that influences locomotion in Limulus
      can be entrained by imposed artificial tides. In the laboratory, these tidal cues
      override the influence of light/dark cycles. In their natural habitat, where both
      tidal and photoperiod inputs are typically always present, their activity rhythms
      are likely to be much more complex.

PMID- 18723636
TI  - Rhythms of locomotion expressed by Limulus polyphemus, the American horseshoe
      crab: II. Relationship to circadian rhythms of visual sensitivity.
AB  - In the laboratory, horseshoe crabs express a circadian rhythm of visual
      sensitivity as well as daily and circatidal rhythms of locomotion. The major goal
      of this investigation was to determine whether the circadian clock underlying
      changes in visual sensitivity also modulates locomotion. To address this
      question, we developed a method for simultaneously recording changes in visual
      sensitivity and locomotion. Although every animal (24) expressed consistent
      circadian rhythms of visual sensitivity, rhythms of locomotion were more
      variable: 44% expressed a tidal rhythm, 28% were most active at night, and the
      rest lacked statistically significant rhythms. When exposed to artificial tides,
      8 of 16 animals expressed circatidal rhythms of locomotion that continued after
      tidal cycles were stopped. However, rhythms of visual sensitivity remained stable
      and showed no tendency to be influenced by the imposed tides or locomotor
      activity. These results indicate that horseshoe crabs possess at least two
      biological clocks: one circadian clock primarily used for modulating visual
      sensitivity, and one or more clocks that control patterns of locomotion. This
      arrangement allows horseshoe crabs to see quite well while mating during both
      daytime and nighttime high tides.

PMID- 18723637
TI  - Preliminary observations on the response of Chironex fleckeri (Cnidaria: Cubozoa:
      Chirodropida) to different colors of light.
AB  - Cubozoans are well known for their attraction to light and light-colored objects.
      Two highly venomous types are a public safety concern in Australian waters and
      elsewhere: Chironex fleckeri, long considered the world's deadliest animal and
      colloquially called the box jellyfish; and the irukandjis, a group of at least 10
      species that cause various degrees of debilitating illness. We were asked by the
      tourism industry whether there might be a color of light that box jellyfish and
      irukandjis are not attracted to, such that nighttime diving activities might pose
      less risk of being stung. Our preliminary trials with Chironex fleckeri indicated
      a marked positive response to lights of white, red, yellow, green, orange, and
      blue. All colors elicited a strong and directed attraction to light; however,
      medusae slowed down their pulsation rate, streamed out their tentacles, and
      performed a series of figure-eight patterns back and forth through the lighted
      area when exposed to blue light, which we interpreted as feeding behavior. This
      compares curiously with a report subsequent to our testing, in which the small,
      mangrove-inhabiting cubomedusa Tripedalia cystophora and the beach-dwelling
      Chiropsella bronzie demonstrate a peak sensitivity to blue-green light in the
      region of 500 nm, and that the former is behaviorally attracted to blue and green
      light, but ignores red. This leaves open the possibility that Irukandji species,
      which are more closely related to Tripedalia than to Chironex, may be blind to
      red.

PMID- 18723638
TI  - Cyclophilin and the regulation of symbiosis in Aiptasia pallida.
AB  - The sea anemone Aiptasia pallida, symbiotic with intracellular dinoflagellates,
      expresses a peptydyl-prolyl cis-trans isomerase (PPIase) belonging to the
      conserved family of cytosolic cyclophilins (ApCypA). Protein extracts from A.
      pallida exhibited PPIase activity. Given the high degree of conservation of
      ApCypA and its known function in the cellular stress response, we hypothesized
      that it plays a similar role in the cnidarian-dinoflagellate symbiosis. To
      explore its role, we inhibited the activity of cyclophilin with cyclosporin A
      (CsA). CsA effectively inhibited the PPIase activity of protein extracts from
      symbiotic A. pallida. CsA also induced the dose-dependent release of symbiotic
      algae from host tissues (bleaching). Laser scanning confocal microscopy using
      superoxide and nitric oxide-sensitive fluorescent dyes on live specimens of A.
      pallida revealed that CsA strongly induced the production of these known
      mediators of bleaching. We tested whether the CsA-sensitive isomerase activity is
      important for maintaining the activity of the antioxidant enzyme superoxide
      dismutase (SOD). SOD activity of protein extracts was not affected by pre
      incubation with CsA in vitro.

PMID- 18723639
TI  - Nutritional role of two algal symbionts in the temperate sea anemone Anthopleura
      elegantissima brandt.
AB  - The intertidal sea anemone Anthopleura elegantissima in the Pacific Northwest may
      host a single type of algal symbiont or two different algal symbionts
      simultaneously: zooxanthellae (Symbiodinium muscatinei) and zoochlorellae (green
      algae; Trebouxiophyceae, Chlorophyta). A seasonal comparison of zooxanthellate
      and zoochlorellate anemones showed stable symbiont population densities in summer
      and winter, with densities of zoochlorellae about 4 times those of zooxanthellae.
      Photosynthesis-irradiance curves of freshly isolated symbionts show that the
      productivity (P(max) cell) of freshly isolated zooxanthellae was about 2.5 times
      that of zoochlorellae during July; comparable rates were obtained in other
      months. Models of algal carbon flux show that zoochlorellae may supply the host
      with more photosynthetic carbon per unit anemone biomass than zooxanthellae
      supply. Zooxanthellate anemone tissue was 2 per thousand ((13)C) and 5 per
      thousand ((15)N) enriched and zoochlorellate anemone tissue was 6 per thousand
      ((13)C) and 8 per thousand ((15)N) enriched over their respective symbionts,
      suggesting that zoochlorellate anemones receive less nutrition from their
      symbionts than do zooxanthellate individuals. The disparity between predicted
      contributions from the algal carbon budgets and the stable isotopic composition
      suggests that short-term measures of algal contributions may not reflect actual
      nutritional inputs to the host. Isotopic data support the hypothesis of
      substantial reliance on external food sources. This additional nutrition may
      allow both algae to persist in this temperate intertidal anemone in spite of
      differences in seasonal photosynthetic carbon contributions.

PMID- 18723640
TI  - Morphology and gene analysis of hybrids between two congeneric sea stars with
      different modes of development.
AB  - The sea star Astropecten scoparius has feeding bipinnarian larvae, whereas its
      congener Astropecten latespinosus has nonfeeding barrel-shaped larvae. To
      investigate evolutionary changes in the development of asteroids, we performed
      reciprocal crosses between these two species with different larval forms. In the
      cross between A. scoparius eggs and A. latespinosus sperm, embryos developed into
      bipinnaria-like larvae. The larvae exhibited either a functional digestive system
      (a maternal feature) or a nonfunctional digestive system with the tip of the
      archenteron not connected to the stomodeum (a paternal characteristic). However,
      in the reciprocal cross between A. latespinosus eggs and A. scoparius sperm,
      barrel-shaped larvae resembling those of A. latespinosus were produced, in
      addition to bipinnaria-like larvae, some with functional digestive systems and
      some with nonfunctional ones. Juveniles were produced from all types of crosses.
      18S rDNA was used as a gene marker in cycle sequencing analysis to investigate
      the genetic features of these juveniles. The sequences of juveniles from
      bipinnaria-like larvae showed double-peak nucleotide signals, indicating a
      biparental genome. On the other hand, juveniles from barrel-shaped larvae from A.
      latespinosus eggs and A. scoparius sperm showed the same sequence as A.
      latespinosus juveniles. This suggests that bipinnaria-like larvae of both crosses
      are always hybrids, whereas barrel-shaped larvae develop parthenogenetically.

PMID- 18723641
TI  - Articulated coralline algae of the genus Amphiroa are highly effective natural
      inducers of settlement in the tropical abalone Haliotis asinina.
AB  - The initiation of metamorphosis in marine invertebrates is strongly linked to the
      environment. Planktonic larvae typically are induced to settle and metamorphose
      by external cues such as coralline algae (Corallinaceae, Rhodophyta). Although
      coralline algae are globally abundant, invertebrate larvae of many taxa settle in
      response to a very limited suite of species. This specificity impacts population
      structure, as only locations with the appropriate coralline species can attract
      new recruits. Abalone (Gastropoda, Haliotidae) are among those taxa in which
      closely related species are known to respond to different coralline algae. Here
      we identify highly inductive natural cues of the tropical abalone Haliotis
      asinina. In contrast to reports for other abalone, the greatest proportion of H.
      asinina larvae are induced to settle and metamorphose (92.8% to 100%
      metamorphosis by 48 h postinduction) by articulated corallines of the genus
      Amphiroa. Comparison with field distribution data for different corallines
      suggests larvae are likely to be settling on the seaward side of the reef crest.
      We then compare the response of six different H. asinina larval families to five
      different coralline species to demonstrate that induction by the best inductive
      cue (Amphiroa spp.) effectively extinguishes substantial intraspecific variation
      in the timing of settlement.

PMID- 18723642
TI  - Endonuclease activity of phenol oxidase from Musca domestica larvae.
AB  - Phenol oxidase (PO), a copper-containing enzyme with oxygenase activity, can
      convert mono- or diphenol into quinone and plays an important role in the
      arthropod melanization reaction. Here, we report a new property of PO from Musca
      domestica larvae: a thermotolerant endonuclease activity, by which PO can degrade
      plasmid DNA even after being heated to 80 degrees C for 20 min. We cloned PO
      cDNA, constructed the expression vector pVAX1-PO, and expressed it in HeLa cells.
      The expression product showed the same properties as purified PO. Our data
      indicate that PO is a bifunctional enzyme, exhibiting both oxygenase and
      endonuclease activity, suggesting new roles for this important molecule in the
      innate responses of M. domestica.

PMID- 18723643
TI  - Bacteriophages reduce experimental contamination of hard surfaces, tomato,
      spinach, broccoli, and ground beef by Escherichia coli O157:H7.
AB  - A bacteriophage cocktail (designated ECP-100) containing three Myoviridae phages
      lytic for Escherichia coli O157:H7 was examined for its ability to reduce
      experimental contamination of hard surfaces (glass coverslips and gypsum boards),
      tomato, spinach, broccoli, and ground beef by three virulent strains of the
      bacterium. The hard surfaces and foods contaminated by a mixture of three E. coli
      O157:H7 strains were treated with ECP-100 (test samples) or sterile phosphate
      buffered saline buffer (control samples), and the efficacy of phage treatment was
      evaluated by comparing the number of viable E. coli organisms recovered from the
      test and control samples. Treatments (5 min) with the ECP-100 preparation
      containing three different concentrations of phages (10(10), 10(9), and 10(8)
      PFU/ml) resulted in statistically significant reductions (P = <0.05) of 99.99%,
      98%, and 94%, respectively, in the number of E. coli O157:H7 organisms recovered
      from the glass coverslips. Similar treatments resulted in reductions of 100%,
      95%, and 85%, respectively, in the number of E. coli O157:H7 organisms recovered
      from the gypsum board surfaces; the reductions caused by the two most
      concentrated phage preparations were statistically significant. Treatment with
      the least concentrated preparation that elicited significantly less contamination
      of the hard surfaces (i.e., 10(9) PFU/ml) also significantly reduced the number
      of viable E. coli O157:H7 organisms on the four food samples. The observed
      reductions ranged from 94% (at 120 +/- 4 h posttreatment of tomato samples) to
      100% (at 24 +/- 4 h posttreatment of spinach samples). The data suggest that
      naturally occurring bacteriophages may be useful for reducing contamination of
      various hard surfaces, fruits, vegetables, and ground beef by E. coli O157:H7.

PMID- 18723644
TI  - Early attachment sites for Shiga-toxigenic Escherichia coli O157:H7 in
      experimentally inoculated weaned calves.
AB  - Weaned 3- to 4-month-old calves were fasted for 48 h, inoculated with 10(10) CFU
      of Shiga toxin-positive Escherichia coli (STEC) O157:H7 strain 86-24 (STEC O157)
      or STEC O91:H21 strain B2F1 (STEC O91), Shiga toxin-negative E. coli O157:H7
      strain 87-23 (Stx(-) O157), or a nonpathogenic control E. coli strain, necropsied
      4 days postinoculation, and examined bacteriologically and histologically. Some
      calves were treated with dexamethasone (DEX) for 5 days (3 days before, on the
      day of, and 1 day after inoculation). STEC O157 bacteria were recovered from
      feces, intestines, or gall bladders of 74% (40/55) of calves 4 days after they
      were inoculated with STEC O157. Colon and cecum were sites from which inoculum
      type bacteria were most often recovered. Histologic lesions of attaching-and
      effacing (A/E) O157(+) bacteria were observed in 69% (38/55) of the STEC O157
      inoculated calves. Rectum, ileocecal valve, and distal colon were sites most
      likely to contain A/E O157(+) bacteria. Fecal and intestinal levels of STEC O157
      bacteria were significantly higher and A/E O157(+) bacteria were more common in
      DEX-treated calves than in nontreated calves inoculated with STEC O157. Fecal
      STEC O157 levels were significantly higher than Stx(-) O157, STEC O91, or control
      E. coli; only STEC O157 cells were recovered from tissues. Identifying the
      rectum, ileocecal valve, and distal colon as early STEC O157 colonization sites
      and finding that DEX treatment enhances the susceptibility of weaned calves to
      STEC O157 colonization will facilitate the identification and evaluation of
      interventions aimed at reducing STEC O157 infection in cattle.

PMID- 18723645
TI  - Identification and characterization of lactococcal-prophage-carried
      superinfection exclusion genes.
AB  - Superinfection exclusion (Sie) proteins are prophage-encoded phage resistance
      systems. In this study, genes encoding Sie systems were identified on the genomes
      of Lactococcus lactis subsp. cremoris MG1363 and L. lactis subsp. lactis IL1403.
      These Sie systems are genetically distinct and yet were shown to act specifically
      against a particular subset of the 936 phage group. Each of the systems allows
      normal phage adsorption while affecting plasmid transduction and intracellular
      phage DNA replication, which points to the blocking of phage DNA injection as
      their common mode of action. Sie-specifying genes found on the MG1363 prophages
      are also present in various lactococcal strains, whereas the prophage-encoded Sie
      systems of IL1403 do not appear to be as widely disseminated.

PMID- 18723646
TI  - Formation of nanoscale elemental silver particles via enzymatic reduction by
      Geobacter sulfurreducens.
AB  - Geobacter sulfurreducens reduced Ag(I) (as insoluble AgCl or Ag(+) ions), via a
      mechanism involving c-type cytochromes, precipitating extracellular nanoscale
      Ag(0). These results extend the range of metals known to be reduced by Geobacter
      species and offer a method for recovering silver from contaminated water as
      potentially useful silver nanoparticles.

PMID- 18723647
TI  - Characterization of DegQVh, a serine protease and a protective immunogen from a
      pathogenic Vibrio harveyi strain.
AB  - Vibrio harveyi is an important marine pathogen that can infect a number of
      aquaculture species. V. harveyi degQ (degQ(Vh)), the gene encoding a DegQ
      homologue, was cloned from T4, a pathogenic V. harveyi strain isolated from
      diseased fish. DegQ(Vh) was closely related to the HtrA family members identified
      in other Vibrio species and could complement the temperature-sensitive phenotype
      of an Escherichia coli strain defective in degP. Expression of degQ(Vh) in T4 was
      modulated by temperature, possibly through the sigma(E)-like factor. Enzymatic
      analyses demonstrated that the recombinant DegQ(Vh) protein expressed in and
      purified from E. coli was an active serine protease whose activity required the
      integrity of the catalytic site and the PDZ domains. The optimal temperature and
      pH of the recombinant DegQ(Vh) protein were 50 degrees C and pH 8.0. A
      vaccination study indicated that the purified recombinant DegQ(Vh) was a
      protective immunogen that could confer protection upon fish against infection by
      V. harveyi. In order to improve the efficiency of DegQ(Vh) as a vaccine, a
      genetic construct in the form of the plasmid pAQ1 was built, in which the DNA
      encoding the processed DegQ(Vh) protein was fused with the DNA encoding the
      secretion region of AgaV, an extracellular beta-agarase. The E. coli strain
      harboring pAQ1 could express and secrete the chimeric DegQ(Vh) protein into the
      culture supernatant. Vaccination of fish with viable E. coli expressing chimeric
      degQ(Vh) significantly (P < 0.001) enhanced the survival of fish against V.
      harveyi challenge, which was possibly due to the relatively prolonged exposure of
      the immune system to the recombinant antigen produced constitutively, albeit at a
      gradually decreasing level, by the carrier strain.

PMID- 18723648
TI  - The deep-sea bacterium Photobacterium profundum SS9 utilizes separate flagellar
      systems for swimming and swarming under high-pressure conditions.
AB  - Motility is a critical function needed for nutrient acquisition, biofilm
      formation, and the avoidance of harmful chemicals and predators. Flagellar
      motility is one of the most pressure-sensitive cellular processes in mesophilic
      bacteria; therefore, it is ecologically relevant to determine how deep-sea
      microbes have adapted their motility systems for functionality at depth. In this
      study, the motility of the deep-sea piezophilic bacterium Photobacterium
      profundum SS9 was investigated and compared with that of the related shallow
      water piezosensitive strain Photobacterium profundum 3TCK, as well as that of the
      well-studied piezosensitive bacterium Escherichia coli. The SS9 genome contains
      two flagellar gene clusters: a polar flagellum gene cluster (PF) and a putative
      lateral flagellum gene cluster (LF). In-frame deletions were constructed in the
      two flagellin genes located within the PF cluster (flaA and flaC), the one
      flagellin gene located within the LF cluster (flaB), a component of a putative
      sodium-driven flagellar motor (motA2), and a component of a putative proton
      driven flagellar motor (motA1). SS9 PF flaA, flaC, and motA2 mutants were
      defective in motility under all conditions tested. In contrast, the flaB and
      motA1 mutants were defective only under conditions of high pressure and high
      viscosity. flaB and motA1 gene expression was strongly induced by elevated
      pressure plus increased viscosity. Direct swimming velocity measurements were
      obtained using a high-pressure microscopic chamber, where increases in pressure
      resulted in a striking decrease in swimming velocity for E. coli and a gradual
      reduction for 3TCK which proceeded up to 120 MPa, while SS9 increased swimming
      velocity at 30 MPa and maintained motility up to a maximum pressure of 150 MPa.
      Our results indicate that P. profundum SS9 possesses two distinct flagellar
      systems, both of which have acquired dramatic adaptations for optimal
      functionality under high-pressure conditions.

PMID- 18723650
TI  - Identification of lacto-N-Biose I phosphorylase from Vibrio vulnificus CMCP6.
AB  - A beta-1,3-galactosyl-N-acetylhexosamine phosphorylase (GalGlyNAcP) homolog gene
      was cloned from Vibrio vulnificus CMCP6. In synthetic reactions, the recombinant
      enzyme acted only with GlcNAc and GalNAc as acceptors in the presence of alpha-d
      galactose-1-phosphate as a donor to form lacto-N-biose I (LNB) (Galbeta1 -->
      3GlcNAc) and galacto-N-biose (GNB) (Galbeta1 --> 3GalNAc), respectively. GlcNAc
      was a much better acceptor than GalNAc. The enzyme also phosphorolysed LNB faster
      than it phosphorolysed GNB, and the k(cat)/K(m) for LNB was approximately 60
      times higher than the k(cat)/K(m) for GNB. This result indicated that the enzyme
      was remarkably different from GalGlyNAcP from Bifidobacterium longum, which has
      similar activities with LNB and GNB, and GalGlyNAcP from Clostridium perfringens,
      which is a GNB-specific enzyme. The enzyme is the first LNB-specific enzyme that
      has been found and was designated lacto-N-biose I phosphorylase. The discovery of
      an LNB-specific GalGlyNAcP resulted in recategorization of bifidobacterial
      GalGlyNAcPs as galacto-N-biose/lacto-N-biose I phosphorylases.

PMID- 18723651
TI  - Phylogenetic characterization of two novel commensal bacteria involved with
      innate immune homeostasis in Drosophila melanogaster.
AB  - During a previous study on the molecular interaction between commensal bacteria
      and host gut immunity, two novel bacterial strains, A911(T) and G707(T), were
      isolated from the gut of Drosophila melanogaster. In this study, these strains
      were characterized in a polyphasic taxonomic study using phenotypic, genetic, and
      chemotaxonomic analyses. We show that the strains represent novel species in the
      family Acetobacteraceae. Strain G707(T), a highly pathogenic organism, represents
      a new species in the genus Gluconobacter, "Gluconobacter morbifer" sp. nov. (type
      strain G707 = KCTC 22116(T) = JCM 15512(T)). Strain A911(T), dominantly present
      in the normal Drosphila gut community, represents a novel genus and species,
      designated "Commensalibacter intestini" gen. nov., sp. nov. (type strain A911 =
      KCTC 22117(T) = JCM 15511(T)).

PMID- 18723652
TI  - Isolation and identification of bifidobacteriaceae from human saliva.
AB  - Bifidobacteriaceae were isolated from saliva and infected dentine by using a
      mupirocin-based selective medium. Of the saliva samples, 94% harbored bifids. The
      mean concentration (+/- the standard error) was 4.46 (+/-0.12) log(10)(CFU per ml
      + 1), and the predominant isolates were Bifidobacterium dentium, B. longum,
      Scardovia inopinata, Parascardovia denticolens, and Alloscardovia omnicolens.

PMID- 18723653
TI  - Genetic tools for studying Capnocytophaga canimorsus.
AB  - Capnocytophaga canimorsus, a commensal bacterium from canine oral flora, has been
      isolated throughout the world from severe human infections caused by dog bites.
      Due to the low level of evolutionary relationship to Proteobacteria, genetic
      methods suitable for the genus Capnocytophaga needed to be established. Here, we
      show that Tn4351, derived from Bacteroides fragilis, could be introduced by
      conjugation into C. canimorsus and conferred resistance to erythromycin. By
      mapping and sequencing a naturally occurring plasmid isolated from a clinical
      isolate of C. canimorsus, we identified a repA gene that allowed us to construct
      Escherichia coli-Capnocytophaga shuttle vectors. Most commonly used antibiotic
      markers were not functional in C. canimorsus, but cefoxitin (cfxA), tetracycline
      (tetQ), and erythromycin (ermF) resistances could be used as markers for plasmid
      maintenance in C. canimorsus and even in some other Capnocytophaga spp. Shuttle
      vectors were introduced into C. canimorsus either by conjugation using the origin
      of transfer (oriT) of RP4 or by electrotransformation. Taking advantage of the
      promoter of ermF, an expression vector was constructed. Finally, a method that
      allows site-directed mutagenesis is described. All these genetic tools pave the
      way, not only for molecular studies of the pathogenesis of C. canimorsus, but
      also for studies of other oral Capnocytophaga species.

PMID- 18723654
TI  - Diversity and distribution of commensal fecal Escherichia coli bacteria in beef
      cattle administered selected subtherapeutic antimicrobials in a feedlot setting.
AB  - Escherichia coli strains isolated from fecal samples were screened to examine
      changes in phenotypic and genotypic characteristics including antimicrobial
      susceptibility, clonal type, and carriage of resistance determinants. The goal of
      this 197-day study was to investigate the influence of administration of
      chlortetracycline alone (T) or in combination with sulfamethazine (TS) on the
      development of resistance, dissemination of defined strain types, and prevalence
      of resistance determinants in feedlot cattle. Inherent tetracycline resistance
      was detected in cattle with no prior antimicrobial exposure. Antimicrobial
      administration was not found to be essential for the maintenance of inherently
      ampicillin-resistant and tetracycline-resistant (Tet(r)) E. coli in control
      animals; however, higher Tet(r) E. coli shedding was observed in animals
      subjected to the two treatments. At day 0, high tetracycline (26.7%), lower
      sulfamethoxazole-tetracycline (19.2%), and several other resistances were
      detected, which by the finishing phase (day 197) were restricted to ampicillin
      tetracycline (47.5%), tetracycline (31.7%), and ampicillin-tetracycline
      sulfamethoxazole (20.8%) from both treated and untreated cattle. Among the
      determinants, bla(TEM1), tet(A), and sul2 were prevalent at days 0 and 197.
      Further, E. coli from day 0 showed diverse antibiogram profiles and strain types,
      which by the finishing phase were limited to up to three, irrespective of the
      treatment. Some genetically identical strains expressed different phenotypes and
      harbored diverse determinants, indicating that mobile genetic elements contribute
      to resistance dissemination. This was supported by an increased linked
      inheritance of ampicillin and tetracycline resistance genes and prevalence of
      specific strains at day 197. Animals in the cohort shed increasingly similar
      genotypes by the finishing phase due to animal-to-animal strain transmission.
      Thus, characterizing inherent resistance and propagation of cohort-specific
      strains is crucial for determining antimicrobial resistance in cattle.

PMID- 18723655
TI  - Development of a transposon mutagenesis system in the oral spirochete Treponema
      denticola.
AB  - Here, we report successful transposon mutagenesis in the oral spirochete
      Treponema denticola. A modified Himar1 transposon, including a new antibiotic
      selection cassette for T. denticola, generated mutations affecting cell division,
      transport, and chemotaxis, among other processes. This random mutagenesis system
      should facilitate research on the biology and pathogenesis of this spirochete,
      which is associated with human periodontal diseases.

PMID- 18723649
TI  - Extensive genome rearrangements and multiple horizontal gene transfers in a
      population of pyrococcus isolates from Vulcano Island, Italy.
AB  - The extent of chromosome rearrangements in Pyrococcus isolates from marine
      hydrothermal vents in Vulcano Island, Italy, was evaluated by high-throughput
      genomic methods. The results illustrate the dynamic nature of the genomes of the
      genus Pyrococcus and raise the possibility of a connection between rapidly
      changing environmental conditions and adaptive genomic properties.

PMID- 18723656
TI  - The genome of Polaromonas sp. strain JS666: insights into the evolution of a
      hydrocarbon- and xenobiotic-degrading bacterium, and features of relevance to
      biotechnology.
AB  - Polaromonas sp. strain JS666 can grow on cis-1,2-dichloroethene (cDCE) as a sole
      carbon and energy source and may be useful for bioremediation of chlorinated
      solvent-contaminated sites. Analysis of the genome sequence of JS666 (5.9 Mb)
      shows a bacterium well adapted to pollution that carries many genes likely to be
      involved in hydrocarbon and xenobiotic catabolism and metal resistance. Clusters
      of genes coding for haloalkane, haloalkanoate, n-alkane, alicyclic acid, cyclic
      alcohol, and aromatic catabolism were analyzed in detail, and growth on acetate,
      catechol, chloroacetate, cyclohexane carboxylate, cyclohexanol, ferulate,
      heptane, 3-hydroxybenzoate, hydroxyquinol, gentisate, octane, protocatechuate,
      and salicylate was confirmed experimentally. Strain JS666 also harbors diverse
      putative mobile genetic elements, including retrons, inteins, a miniature
      inverted-repeat transposable element, insertion sequence transposases from 14
      families, eight genomic islands, a Mu family bacteriophage, and two large (338-
      and 360-kb) plasmids. Both plasmids are likely to be self-transferable and carry
      genes for alkane, alcohol, aromatic, and haloacid metabolism. Overall, the JS666
      genome sequence provides insights into the evolution of pollutant-degrading
      bacteria and provides a toolbox of catabolic genes with utility for
      biotechnology.

PMID- 18723657
TI  - Genetic structure and aggressiveness of Erysiphe necator populations during
      grapevine powdery mildew epidemics.
AB  - Isolates of the causal ascomycete of grapevine powdery mildew, Erysiphe necator,
      correspond to two genetically differentiated groups (A and B) that coexist on the
      same host. This coexistence was analyzed by investigating temporal changes in the
      genetic and phenotypic structures of E. necator populations during three
      epidemics. Group A was present only at the start of the growing season, whereas
      group B was present throughout all three epidemics. Group A was less aggressive
      in terms of germination and infection efficiency but was more aggressive than
      group B in terms of the latency period, lesion diameter, and spore production.
      Our results are consistent with a temporal differentiation of niches, preventing
      recombination, and suggest an association between the disease level and the
      frequencies of genetic groups.

PMID- 18723658
TI  - Gram-negative bacterial lipopolysaccharide retention by a positively charged new
      generation filter.
AB  - Removing endotoxins is an important target in the pharmaceutical industry and in
      clinical practice. A filter introduced into an intravenous line prevents
      microbiological contamination, but to date no filters have retained bacterial
      endotoxins. In our study, we assayed a new-generation filter which is able to
      capture endotoxins from solutions.

PMID- 18723659
TI  - Biodegradation of 2-ethylhexyl nitrate by Mycobacterium austroafricanum IFP 2173.
AB  - 2-Ethyhexyl nitrate (2-EHN) is a major additive of fuel that is used to increase
      the cetane number of diesel. Because of its wide use and possible accidental
      release, 2-EHN is a potential pollutant of the environment. In this study,
      Mycobacterium austroafricanum IFP 2173 was selected from among several strains as
      the best 2-EHN degrader. The 2-EHN biodegradation rate was increased in biphasic
      cultures where the hydrocarbon was dissolved in an inert non-aqueous-phase
      liquid, suggesting that the transfer of the hydrophobic substrate to the cells
      was a growth-limiting factor. Carbon balance calculation, as well as organic
      carbon measurement, indicated a release of metabolites in the culture medium.
      Further analysis by gas chromatography revealed that a single metabolite
      accumulated during growth. This metabolite had a molecular mass of 114 Da as
      determined by gas chromatography/mass spectrometry and was provisionally
      identified as 4-ethyldihydrofuran-2(3H)-one by liquid chromatography-tandem mass
      spectrometry analysis. Identification was confirmed by analysis of the chemically
      synthesized lactone. Based on these results, a plausible catabolic pathway is
      proposed whereby 2-EHN is converted to 4-ethyldihydrofuran-2(3H)-one, which
      cannot be metabolized further by strain IFP 2173. This putative pathway provides
      an explanation for the low energetic efficiency of 2-EHN degradation and its poor
      biodegradability.

PMID- 18723660
TI  - Growth temperature exerts differential physiological and transcriptional
      responses in laboratory and wine strains of Saccharomyces cerevisiae.
AB  - Laboratory strains of Saccharomyces cerevisiae have been widely used as a model
      for studying eukaryotic cells and mapping the molecular mechanisms of many
      different human diseases. Industrial wine yeasts, on the other hand, have been
      selected on the basis of their adaptation to stringent environmental conditions
      and the organoleptic properties that they confer to wine. Here, we used a two
      factor design to study the responses of a standard laboratory strain, CEN.PK113
      7D, and an industrial wine yeast strain, EC1118, to growth temperatures of 15
      degrees C and 30 degrees C in nitrogen-limited, anaerobic, steady-state chemostat
      cultures. Physiological characterization revealed that the growth temperature
      strongly impacted the biomass yield of both strains. Moreover, we found that the
      wine yeast was better adapted to mobilizing resources for biomass production and
      that the laboratory yeast exhibited higher fermentation rates. To elucidate
      mechanistic differences controlling the growth temperature response and
      underlying adaptive mechanisms between the strains, DNA microarrays and targeted
      metabolome analysis were used. We identified 1,007 temperature-dependent genes
      and 473 strain-dependent genes. The transcriptional response was used to identify
      highly correlated gene expression subnetworks within yeast metabolism. We showed
      that temperature differences most strongly affect nitrogen metabolism and the
      heat shock response. A lack of stress response element-mediated gene induction,
      coupled with reduced trehalose levels, indicated that there was a decreased
      general stress response at 15 degrees C compared to that at 30 degrees C.
      Differential responses among strains were centered on sugar uptake, nitrogen
      metabolism, and expression of genes related to organoleptic properties. Our study
      provides global insight into how growth temperature affects differential
      physiological and transcriptional responses in laboratory and wine strains of S.
      cerevisiae.

PMID- 18723661
TI  - Salmonella and Escherichia coli O157:H7 contamination on hides and carcasses of
      cull cattle presented for slaughter in the United States: an evaluation of
      prevalence and bacterial loads by immunomagnetic separation and direct plating
      methods.
AB  - The hide and carcass hygiene of cull cattle at slaughter in four geographically
      distant regions of the United States was examined from July 2005 to April 2006 by
      measuring the aerobic plate counts (APC) and the prevalences and loads of
      Salmonella and Escherichia coli O157:H7. The geometric mean log(10) APC CFU/100
      cm(2) levels on hides and preevisceration and postintervention carcasses ranged
      from 6.17 to 8.19, 4.24 to 6.47, and 1.46 to 1.96, respectively, and were highest
      in the summer (P < 0.0001). The average prevalences of Salmonella on hides and
      preevisceration and postintervention carcasses were 89.6% (95% confidence
      interval [CI], 85.1 to 94.0), 50.2% (95% CI, 40.9 to 59.5), and 0.8% (95% CI,
      0.18 to 1.42), respectively. The prevalences of E. coli O157:H7 were 46.9% (95%
      CI, 37.3 to 56.6) and 16.7% (95% CI, 9.8 to 23.6) on hides and preevisceration
      carcasses, respectively. Examination of the concomitant incidence of Salmonella
      and E. coli O157:H7 showed that, on average, 33.3% (95% CI, 15.9 to 69.8) of
      cattle hide and 4.1% (95% CI, 0.98 to 17.3) of preevisceration carcass samples
      were contaminated with both pathogens. The pathogen prevalence on hides and
      carcasses was not significantly affected by the season; however, significant
      differences were observed between plants with respect to the incoming pathogen
      load and the ability to mitigate hide-to-carcass transfer. In spite of these
      differences, postintervention carcass contamination was significantly reduced (P
      < 0.001), likely as a result of the use of one or more of the processing
      interventions employed at each of the four processing plants examined.

PMID- 18723662
TI  - Factors associated with cross-contamination of hides of Scottish cattle by
      Escherichia coli O157.
AB  - The putative source of hide contamination for 236 cattle in Scotland followed
      from the farm through to slaughter was determined using phage and verocytotoxin
      type data. The majority of cattle (84%) were found to have subtypes of
      Escherichia coli O157 on their hide that had not been found previously in any
      animal from the farm of origin, strongly suggesting that contamination occurred
      once animals had left the farm of origin. Using logistic regression analysis,
      several variables and factors were found to be strongly associated (P < 0.01)
      with cross-contamination of cattle hides at the univariate level; commercial
      transport to slaughter, transport with other animals, use of a crush, line
      automation, and increasing slaughterhouse throughput were all risk factors, while
      feeding hay in lairage, processing an animal earlier in a slaughter cohort, and
      cleaning the landing area poststunning were protective. In the multivariable
      model, with the slaughterhouse and the farm group included as random effects,
      factors associated with the cross-contamination of cattle hides were identified.
      Transport to the slaughterhouse by a commercial hauler had a borderline
      significant association with increased odds of an animal having a cross
      contaminated hide (odds ratio [OR] [95% confidence interval (CI)] = 5.7 [0.99,
      33.0]; P = 0.05). At the slaughterhouse, providing hay to cattle waiting in
      lairage (OR [95% CI] = 0.04 [<0.01, 1.04]; P = 0.05) and cleaning the landing
      area (OR [95% CI] = 0.03 [<0.01, 1.15,]; P = 0.06) also had a borderline
      significant association with decreased odds of an animal having a cross
      contaminated hide. Although the prevalence of carcass contamination remains very
      low, targeted intervention at the preslaughter stage may have the potential to
      reduce further the risk to public health.

PMID- 18723663
TI  - Crenarchaeota and their role in the nitrogen cycle in a subsurface radioactive
      thermal spring in the Austrian Central Alps.
AB  - Previous results from a 16S rRNA gene library analysis showed high diversity
      within the prokaryotic community of a subterranean radioactive thermal spring,
      the "Franz-Josef-Quelle" (FJQ) in Bad Gastein, Austria, as well as evidence for
      ammonia oxidation by crenarchaeota. This study reports further characterization
      of the community by denaturing gradient gel electrophoresis (DGGE) analysis,
      fluorescence in situ hybridization (FISH), and semiquantitative nitrification
      measurements. DGGE bands from three types of samples (filtered water, biofilms on
      glass slides, and naturally grown biofilms), including samples collected at two
      distinct times (January 2005 and July 2006), were analyzed. The archaeal
      community consisted mainly of Crenarchaeota of the soil-subsurface-freshwater
      group (group 1.1b) and showed a higher diversity than in the previous 16S rRNA
      gene library analysis, as was also found for crenarchaeal amoA genes. No
      bacterial amoA genes were detected. FISH analysis of biofilms indicated the
      presence of archaeal cells with an abundance of 5.3% (+/-4.5%) in the total 4',6
      diamidino-2-phenylindole (DAPI)-stained community. Microcosm experiments of
      several weeks in duration showed a decline of ammonium that correlated with an
      increase of nitrite, the presence of crenarchaeal amoA genes, and the absence of
      bacterial amoA genes. The data suggested that only ammonia-oxidizing archaea
      (AOA) perform the first step of nitrification in this 45 degrees C environment.
      The crenarchaeal amoA gene sequences grouped within a novel cluster of amoA
      sequences from the database, originating from geothermally influenced
      environments, for which we propose the designation "thermal spring" cluster and
      which may be older than most AOA from soils on earth.

PMID- 18723664
TI  - Characterization and deposition of respirable large- and small-particle
      bioaerosols.
AB  - The deposition patterns of large-particle microbiological aerosols within the
      respiratory tract are not well characterized. A novel system (the flow-focusing
      aerosol generator [FFAG]) which enables the generation of large (>10-microm)
      aerosol particles containing microorganisms under laboratory conditions was
      characterized to permit determination of deposition profiles within the murine
      respiratory tract. Unlike other systems for generating large aerosol particles,
      the FFAG is compatible with microbiological containment and the inhalational
      challenge of animals. By use of entrapped Escherichia coli cells, Bacillus
      atrophaeus spores, or FluoSphere beads, the properties of aerosols generated by
      the FFAG were compared with the properties of aerosols generated using the
      commonly available Collison nebulizer, which preferentially generates small (1-
      to 3-microm) aerosol particles. More entrapped particulates (15.9- to 19.2-fold)
      were incorporated into 9- to 17-microm particles generated by the FFAG than by
      the Collison nebulizer. The 1- to 3-microm particles generated by the Collison
      nebulizer were more likely to contain a particulate than those generated by the
      FFAG. E. coli cells aerosolized using the FFAG survived better than those
      aerosolized using the Collison nebulizer. Aerosols generated by the Collison
      nebulizer and the FFAG preferentially deposited in the lungs and nasal passages
      of the murine respiratory tract, respectively. However, significant deposition of
      material also occurred in the gastrointestinal tract after inhalation of both the
      small (89.7%)- and large (61.5%)-particle aerosols. The aerosols generated by the
      Collison nebulizer and the FFAG differ with respect to mass distribution,
      distribution of the entrapped particulates, bacterial survival, and deposition
      within the murine respiratory tract.

PMID- 18723665
TI  - Fragment-HMM: a new approach to protein structure prediction.
AB  - We designed a simple position-specific hidden Markov model to predict protein
      structure. Our new framework naturally repeats itself to converge to a final
      target, conglomerating fragment assembly, clustering, target selection,
      refinement, and consensus, all in one process. Our initial implementation of this
      theory converges to within 6 A of the native structures for 100% of decoys on all
      six standard benchmark proteins used in ROSETTA (discussed by Simons and
      colleagues in a recent paper), which achieved only 14%-94% for the same data. The
      qualities of the best decoys and the final decoys our theory converges to are
      also notably better.

PMID- 18723666
TI  - Independently silencing two photosynthetic proteins in Nicotiana attenuata has
      different effects on herbivore resistance.
AB  - Insect attack frequently down-regulates photosynthetic proteins. To understand
      how this influences the plant-insect interaction, we transformed Nicotiana
      attenuata to independently silence ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RuBPCase) activase (RCA) and RuBPCase and selected lines
      whose photosynthetic capacity was similarly reduced. Decreases in plant growth
      mirrored the decreases in photosynthesis, but the effects on herbivore
      performance differed. Both generalist (Spodoptera littoralis) and specialist
      (Manduca sexta) larvae grew larger on RCA-silenced plants, which was consistent
      with decreased levels of trypsin protease inhibitors and diterpene glycosides and
      increased levels of RuBPCase, the larvae's main dietary protein. RCA-silenced
      plants were impaired in their attack-elicited jasmonate (JA)-isoleucine
      (Ile)/leucine levels, but RuBPCase-silenced plants were not, a deficiency that
      could not be restored by supplementation with Ile or attributed to lower
      transcript levels of JAR4/6, the key enzyme for JA-Ile conjugation. From these
      results, we infer that JA-Ile/leucine signaling and the herbivore resistance
      traits elicited by JA-Ile are influenced by adenylate charge, or more generally,
      carbon availability in RCA- but not RuBPCase-silenced plants. Growth of
      generalist larvae on RuBPCase-silenced plants did not differ from growth on empty
      vector controls, but the specialist larvae grew faster on RuBPCase-silenced
      plants, which suggests that the specialist can better tolerate the protein
      deficiency resulting from RuBPCase silencing than the generalist can. We conclude
      that the plant-herbivore interaction is more influenced by the particular
      mechanisms that reduce photosynthetic capacity after herbivore attack than by the
      magnitude of the decrease, which highlights the value of understanding defense
      mechanisms in evaluating growth-defense tradeoffs.

PMID- 18723667
TI  - Abnormal chloroplast development and growth inhibition in rice thioredoxin m
      knock-down plants.
AB  - Plant cells contain several thioredoxin isoforms that are characterized by
      subcellular localization and substrate specificity. Here, we describe the
      functional characterization of a rice (Oryza sativa) thioredoxin m isoform
      (Ostrxm) using a reverse genetics technique. Ostrxm showed green tissue-specific
      and light-responsive mRNA expression. Ostrxm was localized in chloroplasts of
      rice mesophyll cells, and the recombinant protein showed dithiothreitol-dependent
      insulin beta-chain reduction activity in vitro. RNA interference (RNAi) of Ostrxm
      resulted in rice plants with developmental defects, including semidwarfism, pale
      green leaves, abnormal chloroplast structure, and reduced carotenoid and
      chlorophyll content. Ostrxm RNAi plants showed remarkably decreased F(v)/F(m)
      values under high irradiance conditions (1,000 micromol m(-2) s(-1)) with delayed
      recovery. Two-dimensional electrophoresis and matrix-assisted laser
      desorption/ionization time-of-flight analysis showed that the levels of several
      chloroplast proteins critical for photosynthesis and biogenesis were
      significantly decreased in Ostrxm RNAi plants. Furthermore, 2-Cys peroxiredoxin,
      a known target of thioredoxin, was present in oxidized forms, and hydrogen
      peroxide levels were increased in Ostrxm RNAi plants. The pleiotropic effects of
      Ostrxm RNAi suggest that Ostrxm plays an important role in the redox regulation
      of chloroplast target proteins involved in diverse physiological functions.

PMID- 18723668
TI  - 4-Chloro-alpha-cyanocinnamic acid is an advanced, rationally designed MALDI
      matrix.
AB  - Matrix-assisted laser desorption ionization (MALDI) has become an enabling
      technology for the fields of protein mass spectrometry (MS) and proteomics.
      Despite its widespread use, for example, in protein identification via peptide
      mass fingerprinting, a comprehensive model for the generation of free gas-phase
      ions has not yet been developed. All matrices in use today, such as alpha-cyano-4
      hydroxycinnamic acid (CHCA), have been found empirically and stem from the early
      days of MALDI. By systematic and targeted variation of the functional groups of
      the alpha-cyanocinnamic acid core unit, 4-chloro-alpha-cyanocinnamic acid (Cl
      CCA) was selected and synthesized, and it exhibited outstanding matrix
      properties. Key features are a substantial increase in sensitivity and a
      considerably enhanced peptide recovery in proteomic analyses because of a much
      more uniform response to peptides of different basicity. Using Cl-CCA as a matrix
      for a 1 fmol bovine serum albumin (BSA) in-solution digest, the sequence coverage
      is raised to 48%, compared with 4% for CHCA. For a gel band containing 25 fmol of
      BSA, unambiguous protein identification becomes possible with Cl-CCA. These
      findings also imply ion formation via a chemical ionization mechanism with proton
      transfer from a reactive protonated matrix species to the peptide analytes. The
      considerable increase in performance promises to have a strong impact on future
      analytical applications of MALDI, because current sensitivity limits are overcome
      and more comprehensive analyses come into reach.

PMID- 18723669
TI  - Energy-dependent fitness: a quantitative model for the evolution of yeast
      transcription factor binding sites.
AB  - We present a genomewide cross-species analysis of regulation for broad-acting
      transcription factors in yeast. Our model for binding site evolution is founded
      on biophysics: the binding energy between transcription factor and site is a
      quantitative phenotype of regulatory function, and selection is given by a
      fitness landscape that depends on this phenotype. The model quantifies
      conservation, as well as loss and gain, of functional binding sites in a coherent
      way. Its predictions are supported by direct cross-species comparison between
      four yeast species. We find ubiquitous compensatory mutations within functional
      sites, such that the energy phenotype and the function of a site evolve in a
      significantly more constrained way than does its sequence. We also find evidence
      for substantial evolution of regulatory function involving point mutations as
      well as sequence insertions and deletions within binding sites. Genes lose their
      regulatory link to a given transcription factor at a rate similar to the neutral
      point mutation rate, from which we infer a moderate average fitness advantage of
      functional over nonfunctional sites. In a wider context, this study provides an
      example of inference of selection acting on a quantitative molecular trait.

PMID- 18723670
TI  - Targeting the stromal androgen receptor in primary prostate tumors at earlier
      stages.
AB  - To differentiate roles of androgen receptor (AR) in prostate stromal and
      epithelial cells, we have generated inducible-(ind)ARKO-TRAMP and prostate
      epithelial-specific ARKO TRAMP (pes-ARKO-TRAMP) mouse models, in which the AR was
      knocked down in both prostate epithelium and stroma or was knocked out in the
      prostate epithelium, respectively. We found that loss of AR in both mouse models
      resulted in poorly differentiated primary tumors with expanded intermediate cell
      populations. Interestingly, knockdown of both epithelial and stromal AR in ind
      ARKO-TRAMP mice at earlier stages resulted in smaller primary prostate tumors
      with lower proliferation rates, and knockout of AR in pes-ARKO-TRAMP mice
      resulted in larger primary prostate tumors with higher proliferation rates. The
      differential proliferation rates, yet with similarly expanded intermediate cell
      populations, indicated that the prostate stromal AR might play a more dominant
      role than the epithelial AR to promote primary tumor proliferation at an early
      stage of tumor. Tissue recombination of human prostate stromal cell lines (WPMY1
      v or WPMY1-ARsi) with human prostate cancer epithelial cell lines (PC3-v or PC3
      AR9) further demonstrated that the AR might function as a suppressor in
      epithelial cells and a proliferator in stromal cells in the primary prostate
      tumors. The dual roles of the AR in prostate epithelium and stroma may require us
      to reevaluate the target and timing of androgen-deprivation therapy for prostate
      cancer patients and may suggest a need to develop new drugs to selectively target
      stromal AR in the primary prostate tumors at earlier stages.

PMID- 18723671
TI  - A starvation-induced noncoding RNA modulates expression of Dicer-regulated genes.
AB  - Although much has been learned about short noncoding RNAs, long noncoding
      transcripts are largely uncharacterized. Here, we describe Caenorhabditis elegans
      rncs-1, a highly base-paired, 800-nucleotide noncoding RNA expressed in
      hypodermis and intestine. Transcription of rncs-1 is modulated in response to
      food supply. Although highly double-stranded, we show that rncs-1 RNA is not a
      substrate for Dicer because of branched structures at its termini. However, rncs
      1 RNA inhibits Dicer cleavage of a second dsRNA in vitro, presumably by
      competition. We validate this observation in vivo by demonstrating that mRNA
      levels of several Dicer-regulated genes vary with changes in rncs-1 expression.
      Certain viruses express dsRNA to compete with cellular dsRNA-mediated pathways,
      and our data suggest that rncs-1 provides a cellular correlate of this
      phenomenon.

PMID- 18723672
TI  - Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29
      in cardiac fibrosis.
AB  - Acute myocardial infarction (MI) due to coronary artery occlusion is accompanied
      by a pathological remodeling response that includes hypertrophic cardiac growth
      and fibrosis, which impair cardiac contractility. Previously, we showed that
      cardiac hypertrophy and heart failure are accompanied by characteristic changes
      in the expression of a collection of specific microRNAs (miRNAs), which act as
      negative regulators of gene expression. Here, we show that MI in mice and humans
      also results in the dysregulation of specific miRNAs, which are similar to but
      distinct from those involved in hypertrophy and heart failure. Among the MI
      regulated miRNAs are members of the miR-29 family, which are down-regulated in
      the region of the heart adjacent to the infarct. The miR-29 family targets a
      cadre of mRNAs that encode proteins involved in fibrosis, including multiple
      collagens, fibrillins, and elastin. Thus, down-regulation of miR-29 would be
      predicted to derepress the expression of these mRNAs and enhance the fibrotic
      response. Indeed, down-regulation of miR-29 with anti-miRs in vitro and in vivo
      induces the expression of collagens, whereas over-expression of miR-29 in
      fibroblasts reduces collagen expression. We conclude that miR-29 acts as a
      regulator of cardiac fibrosis and represents a potential therapeutic target for
      tissue fibrosis in general.

PMID- 18723673
TI  - Subclonal phylogenetic structures in cancer revealed by ultra-deep sequencing.
AB  - During the clonal expansion of cancer from an ancestral cell with an initiating
      oncogenic mutation to symptomatic neoplasm, the occurrence of somatic mutations
      (both driver and passenger) can be used to track the on-going evolution of the
      neoplasm. All subclones within a cancer are phylogenetically related, with the
      prevalence of each subclone determined by its evolutionary fitness and the timing
      of its origin relative to other subclones. Recently developed massively parallel
      sequencing platforms promise the ability to detect rare subclones of genetic
      variants without a priori knowledge of the mutations involved. We used ultra-deep
      pyrosequencing to investigate intraclonal diversification at the Ig heavy chain
      locus in 22 patients with B-cell chronic lymphocytic leukemia. Analysis of a non
      polymorphic control locus revealed artifactual insertions and deletions resulting
      from sequencing errors and base substitutions caused by polymerase
      misincorporation during PCR amplification. We developed an algorithm to
      differentiate genuine haplotypes of somatic hypermutations from such artifacts.
      This proved capable of detecting multiple rare subclones with frequencies as low
      as 1 in 5000 copies and allowed the characterization of phylogenetic
      interrelationships among subclones within each patient. This study demonstrates
      the potential for ultra-deep resequencing to recapitulate the dynamics of clonal
      evolution in cancer cell populations.

PMID- 18723674
TI  - Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety,
      and lower survival under stress conditions.
AB  - The adrenomedullin (AM) gene, adm, is widely expressed in the central nervous
      system (CNS) and several functions have been suggested for brain AM. Until now, a
      formal confirmation of these actions using genetic models has been elusive since
      the systemic adm knockout results in embryo lethality. We have built a
      conditional knockout mouse model using the Cre/loxP approach. When crossed with
      transgenic mice expressing the Cre recombinase under the tubulin Talpha-1
      promoter, we obtained animals with no AM expression in the CNS but normal levels
      in other organs. These animals lead normal lives and do not present any gross
      morphological defect. Specific areas of the brain of animals lacking CNS AM
      contain hyperpolymerized tubulin, a consequence of AM downregulation. Behavioral
      analysis shows that mice with no AM in their brain have impaired motor
      coordination and are hyperactive and overanxious when compared to their wild-type
      littermates. Treatment with methylphenidate, haloperidol, and diazepam did not
      show differences between genotypes. Circulating levels of adrenocorticotropic
      hormone and corticosterone were similar in knockout and wild-type mice. Animals
      with no brain AM were less resistant to hypobaric hypoxia than wild-type mice,
      demonstrating the neuroprotective function of AM in the CNS. In conclusion, AM
      exerts a beneficial action in the brain by maintaining homeostasis both under
      normal and stress conditions.

PMID- 18723675
TI  - RPA phosphorylation facilitates mitotic exit in response to mitotic DNA damage.
AB  - Human replication protein A (RPA) becomes phosphorylated on the RPA2 subunit by
      cyclin B-Cdc2 during mitosis, although the functional role of this modification
      is unclear. We find that this modification stimulates RPA2 to become
      hyperphosphorylated in response to mitotic DNA damage caused by bleomycin
      treatment. Cells in which endogenous RPA2 was replaced by a mutant subunit
      lacking both Cdc2 sites had a significant defect in mitotic release into a 2N
      G(1) phase after exposure to bleomycin. An increased percentage of these mutant
      cells also was positive initially for cyclin B expression and BubR1 chromatin
      staining, indicative of an extended spindle assembly checkpoint. The mutant cells
      that experienced mitotic DNA damage also underwent apoptosis at higher levels
      than cells expressing the WT subunit. Even so, we did not find the mutation had
      any dramatic effects on the level of DNA repair in mitosis. Cells lacking ATM (a
      checkpoint factor and RPA2 kinase) also were severely defective in mitotic exit
      and were unable to support RPA hyperphosphorylation after mitotic DNA damage.
      Although checkpoint 1 effector kinase (Chk1) had a more complex role, inhibition
      of Chk1 activity with UCN-01 also reduced mitotic exit. Chk1 activation and
      mitotic RPA hyperphosphorylation were found to be independent events. Our results
      demonstrate that mitotic RPA hyperphosphorylation facilitates release of cells
      from a damaged mitosis into a 2N G(1) phase, thereby increasing cell viability.

PMID- 18723676
TI  - A critical role for the right fronto-insular cortex in switching between central
      executive and default-mode networks.
AB  - Cognitively demanding tasks that evoke activation in the brain's central
      executive network (CEN) have been consistently shown to evoke decreased
      activation (deactivation) in the default-mode network (DMN). The neural
      mechanisms underlying this switch between activation and deactivation of large
      scale brain networks remain completely unknown. Here, we use functional magnetic
      resonance imaging (fMRI) to investigate the mechanisms underlying switching of
      brain networks in three different experiments. We first examined this switching
      process in an auditory event segmentation task. We observed significant
      activation of the CEN and deactivation of the DMN, along with activation of a
      third network comprising the right fronto-insular cortex (rFIC) and anterior
      cingulate cortex (ACC), when participants perceived salient auditory event
      boundaries. Using chronometric techniques and Granger causality analysis, we show
      that the rFIC-ACC network, and the rFIC, in particular, plays a critical and
      causal role in switching between the CEN and the DMN. We replicated this causal
      connectivity pattern in two additional experiments: (i) a visual attention
      "oddball" task and (ii) a task-free resting state. These results indicate that
      the rFIC is likely to play a major role in switching between distinct brain
      networks across task paradigms and stimulus modalities. Our findings have
      important implications for a unified view of network mechanisms underlying both
      exogenous and endogenous cognitive control.

PMID- 18723677
TI  - Autoinhibitory regulation of SCF-mediated ubiquitination by human cullin 1's C
      terminal tail.
AB  - SCF (Skp1 x CUL1 x F-box protein x ROC1) E3 ubiquitin ligase and Cdc34 E2
      conjugating enzyme catalyze polyubiquitination in a precisely regulated fashion.
      Here, we describe biochemical evidence suggesting an autoinhibitory role played
      by the human CUL1 ECTD (extreme C-terminal domain; spanning the C-terminal 50
      amino acids), a region that is predicted to contact the ROC1 RING finger protein
      by structural studies. We showed that ECTD did not contribute to CUL1's stable
      association with ROC1. Remarkably, deletion of ECTD, or missense mutations
      designed to disrupt the predicted ECTD x ROC1 interaction, markedly increased the
      ability of SCF(betaTrCP2) to promote IkappaB alpha polyubiquitination and
      polyubiquitin chain assembly by Cdc34 in vitro. Thus, disruption of ECTD yields
      in vitro effects that parallel SCF activation by Nedd8 conjugation to CUL1. We
      propose that SCF may be subject to autoinhibitory regulation, in which Nedd8
      conjugation acts as a molecular switch to drive the E3 into an active state by
      diminishing the inhibitory ECTD x ROC1 interaction.

PMID- 18723678
TI  - Role of glycan synthesis in colonization of the mammalian gut by the bacterial
      symbiont Bacteroides fragilis.
AB  - Bacteroides species are the most abundant Gram-negative bacteria of the human
      colonic microbiota. These endogenous organisms are unique in that they synthesize
      an extensive number of phase-variable surface polysaccharides. Pathogenic
      bacteria phase vary expression of surface molecules for immune evasion, but the
      importance of the synthesis of multiple phase-variable polysaccharides to these
      commensal bacteria is unknown. We previously showed that a Bacteroides fragilis
      mutant unable to synthesize 4 of the 8 capsular polysaccharides and unable to
      glycosylate proteins properly is rapidly outcompeted by the wild-type strain for
      colonization of the gnotobiotic mouse intestine. In the present study, we
      constructed mutants defective only in capsule polysaccharide synthesis to define
      better the importance of these surface molecules to intestinal colonization. We
      discovered a key enzymatic activity required for synthesis of 7 of the 8 capsular
      polysaccharides. Deletion of its gene resulted in the first B. fragilis mutant
      able to synthesize only one phase-variable polysaccharide, and further mutation
      resulted in a stable acapsular mutant. We show that the acapsular mutant is
      rapidly outcompeted, but synthesis of a single polysaccharide is sufficient for
      the organism to colonize the gnotobiotic intestine competitively. These data
      demonstrate that initial colonization of the gnotobiotic mouse intestine by B.
      fragilis requires that the organism synthesize only a single polysaccharide and
      suggest that the synthesis of multiple phase-variable polysaccharides is
      important for the bacteria's long-term maintenance in the normally complex and
      competitive ecosystem.

PMID- 18723679
TI  - Androgen receptor is a tumor suppressor and proliferator in prostate cancer.
AB  - Targeting androgens/androgen receptor (AR) functions via androgen deprivation
      therapy (ADT) remains the standard treatment for prostate cancer. However, most
      tumors eventually recur despite ADT. Here we demonstrate that the prostate AR may
      function as both a suppressor and a proliferator to suppress or promote prostate
      cancer metastasis. Results from orthotopically recombining stromal WPMY1 cells
      with epithelial PC3 prostate cancer cells in mice demonstrated that restoring AR
      in epithelial PC3 cells or knockdown of AR in stromal WPMY1 cells suppressed
      prostate cancer metastasis. Knockdown of the AR in epithelial CWR22rv1 prostate
      cancer cells also resulted in increased cell invasion in vitro and in vivo.
      Restoring AR in PC3 cells (PC3-AR9) results in decreased invasion in bone lesion
      assays and in vivo mouse models. Mice lacking the prostate epithelial AR have
      increased apoptosis in epithelial luminal cells and increased proliferation in
      epithelial basal cells. The consequences of these two contrasting results led to
      the expansion of CK5/CK8-positive intermediate cells, and mice developed larger
      and more invasive metastatic tumors in lymph nodes and died earlier than wild
      type littermates. Mechanistic dissection suggested that androgens/AR might
      directly or indirectly modulate metastasis-related genes and suppression of
      TGFbeta1 signals results in the partial inhibition of AR-mediated metastasis.
      Collectively, our understanding of these opposing roles of prostatic AR may
      revolutionize the way we combat prostate cancer, and allow the development of new
      and better therapies by targeting only the proliferative role of AR.

PMID- 18723680
TI  - Executioner caspase-3 and caspase-7 are functionally distinct proteases.
AB  - Members of the caspase family of cysteine proteases play central roles in
      coordinating the stereotypical events that occur during apoptosis. Because the
      major executioner caspases, caspase-3 and caspase-7, exhibit almost
      indistinguishable activity toward certain synthetic peptide substrates, this has
      led to the widespread view that these proteases occupy functionally redundant
      roles within the cell death machinery. However, the distinct phenotypes of mice
      deficient in either of these caspases, as well as mice deficient in both, is at
      odds with this view. These distinct phenotypes could be related to differences in
      the relative expression levels of caspase-3 and caspase-7 in vivo, or due to more
      fundamental differences between these proteases in terms of their ability to
      cleave natural substrates. Here we show that caspase-3 and caspase-7 exhibit
      differential activity toward multiple substrate proteins, including Bid, XIAP,
      gelsolin, caspase-6, and cochaperone p23. Caspase-3 was found to be generally
      more promiscuous than caspase-7 and appears to be the major executioner caspase
      during the demolition phase of apoptosis. Our observations provide a molecular
      basis for the different phenotypes seen in mice lacking either caspase and
      indicate that these proteases occupy nonredundant roles within the cell death
      machinery.

PMID- 18723681
TI  - Photoprotective role of NADPH:protochlorophyllide oxidoreductase A.
AB  - A homology model of NADPH:protochlorophyllide (Pchlide) oxidoreductase A (POR;
      E.C. 1.3.33.1) of barley is developed and verified by site-directed mutagenesis.
      PORA is considered a globular protein consisting of nine alpha-helices and seven
      beta-strands. The model predicts the presence of two functionally distinctive
      Pchlide binding sites where the pigment is coordinated by cysteine residues. The
      pigment bound to the first, high-affinity Pchlide binding site is used for the
      formation of the photoactive state of the enzyme. The pigment bound to the
      second, low-affinity Pchlide binding site is involved in the PORA:PORB
      interaction, allowing for resonance energy transfer between the neighboring PORs
      in the complex. In the in vitro reconstituted light-harvesting POR:Pchlide
      complex (LHPP), light absorbed by PORA-bound Pchlide b is transferred to PORB
      bound Pchlide a. That induces the conversion of Pchlide a to chlorophyllide
      (Chlide) a. This energy transfer eliminates the possibility of Pchlide b
      photoreduction and prevents that excited triplet states of either Pchlides a or b
      accumulate and provoke singlet oxygen production. Together, our results provide a
      photoprotective role of PORA during greening.

PMID- 18723682
TI  - Structure of Vps75 and implications for histone chaperone function.
AB  - The vacuolar protein sorting 75 (Vps75) histone chaperone participates in
      chromatin assembly and disassembly at both active and inactive genes through the
      preferential binding to histone H3-H4. Vps75 is also one of two histone
      chaperones, along with antisilencing factor 1, that promotes histone H3-Lys-56
      acetylation by the regulation of Ty1 transposition protein 109 (Rtt109) histone
      acetyltransferase. Here, we report the x-ray crystal structure of Vps75 and carry
      out biochemical studies to characterize its interaction with Rtt109. We find that
      the Vps75 structure forms a homodimeric "headphone" architecture that includes an
      extended helical dimerization domain and earmuff domains at opposite ends and
      sides of the dimerization domain. Despite the similar overall architecture with
      the yeast nucleosome assembly protein 1 and human SET/TAF-1beta/INHAT histone
      chaperones, Vps75 shows several unique features including the relative
      disposition of the earmuff domains to the dimerization domain, characteristics of
      the earmuff domains, and a pronounced cleft at the center of the Vps75 dimer.
      These differences appear to correlate with the unique function of Vps75 to
      interact with Rtt109 for histone acetylation. Our biochemical studies reveal that
      two surfaces on the earmuff domain of Vps75 participate in Rtt109 interaction
      with a stoichiometry of 2:1, thus leaving the pronounced central cleft of the
      Vps75 dimer largely accessible for histone binding. Taken together, our data
      provide a structural framework for understanding how Vps75 mediates both
      nucleosome assembly and histone acetylation by Rtt109.

PMID- 18723684
TI  - The Rab5 guanylate exchange factor Rin1 regulates endocytosis of the EphA4
      receptor in mature excitatory neurons.
AB  - Ephrin signaling through Eph receptor tyrosine kinases regulates important
      morphogenetic events during development and synaptic plasticity in the adult
      brain. Although Eph-ephrin endocytosis is required for repulsive axon guidance,
      its role in postnatal brain and synaptic plasticity is unknown. Here, we show
      that Rin1, a postnatal brain-specific Rab5-GEF, is coexpressed with EphA4 in
      excitatory neurons and interacts with EphA4 in synaptosomal fractions. The
      interaction of Rin1 and EphA4 requires Rin1's SH2 domain, consistent with the
      view that Rin1 targets tyrosine phosphorylated receptors to Rab5 compartments. We
      find that Rin1 mediates EphA4 endocytosis in postnatal amygdala neurons after
      engagement of EphA4 with its cognate ligand ephrinB3. Rin1 was shown to suppress
      synaptic plasticity in the amygdala, a forebrain structure important for fear
      learning, possibly by internalizing synaptic receptors. We find that the EphA4
      receptor is required for synaptic plasticity in the amygdala, raising the
      possibility that an underlying mechanism of Rin1 function in amygdala is to down
      regulate EphA4 signaling by promoting its endocytosis.

PMID- 18723683
TI  - Rapid tolerization of virus-activated tumor-specific CD8+ T cells in prostate
      tumors of TRAMP mice.
AB  - To study T cell responses to tumors in an autochthonous model, we expressed a CD8
      T cell epitope SIYRYYGL (SIY) in the prostate of transgenic adenocarcinoma
      (TRAMP) mice (referred to as TRP-SIY), which spontaneously develop prostate
      cancer. Naive SIY-specific CD8 T cells adoptively transferred into TRP-SIY mice
      became tolerized in the prostate draining lymph nodes. Vaccination of TRP-SIY
      mice intranasally with influenza virus that expresses the SIY epitope resulted in
      generation of SIY-specific effector T cells in the lung-draining lymph nodes.
      These effector T cells expressed TNFalpha and IFNgamma, eliminated SIY peptide
      loaded target cells in vivo, and infiltrated prostate tumors, where they rapidly
      lost the ability to produce effector cytokines. A population of these T cells
      persisted in prostate tumors but not in lymphoid organs and could be induced to
      re-express effector functions following cytokine treatment in vitro. These
      findings suggest that T cells of a given clone can be activated and tolerized
      simultaneously in different microenvironments of the same host and that effector
      T cells are rapidly tolerized in the tumors. Our model provides a system to study
      T cell-tumor interactions in detail and to test the efficacy of cancer
      immunotherapeutic strategies.

PMID- 18723685
TI  - Direct observation of reaction intermediates for a well defined heterogeneous
      alkene metathesis catalyst.
AB  - Grafting of [W([triple bond]NAr)(=CHtBu)(2,5-Me(2)NC(4)H(2))(2)] on a silica
      partially dehydroxylated at 700 degrees C (SiO(2- (700))) generates the
      corresponding monosiloxy complex [([triple bond]SiO)W([triple
      bond]NAr)(=CHtBu)(2,5-Me(2)NC(4)H(2))] as the major species (approximately 90%)
      along with [([triple bond]SiO)W([triple bond]NAr)(CH(2)tBu)(2,5
      Me(2)NC(4)H(2))(2)], according to mass balance analysis, IR, and NMR studies.
      This heterogeneous catalyst displays good activity and stability in the
      metathesis of propene. Very importantly, solid state NMR spectroscopy allows
      observation of the propagating alkylidene as well as stable metallacyclobutane
      intermediates. These species have the same reactivity as the initial surface
      complex [([triple bond]SiO)W([triple bond]NAr)(=CHtBu)(2,5-Me(2)NC(4)H(2))],
      which shows that they are the key intermediates of alkene metathesis.

PMID- 18723686
TI  - Structural plasticity with preserved topology in the postsynaptic protein
      network.
AB  - The size, shape, and molecular arrangement of the postsynaptic density (PSD)
      determine the function of excitatory synapses in the brain. Here, we directly
      measured the internal dynamics of scaffold proteins within single living PSDs,
      focusing on the principal scaffold protein PSD-95. We found that individual PSDs
      undergo rapid, continuous changes in morphology driven by the actin cytoskeleton
      and regulated by synaptic activity. This structural plasticity is accompanied by
      rapid fluctuations in internal scaffold density over submicron distances. Using
      targeted photobleaching and photoactivation of PSD subregions, we show that PSD
      95 is nearly immobile within the PSD, and PSD subdomains can be maintained over
      long periods. We propose a flexible matrix model of the PSD based on stable
      molecular positioning of PSD-95 scaffolds.

PMID- 18723687
TI  - Synapse formation and clustering of neuroligin-2 in the absence of GABAA
      receptors.
AB  - GABAergic synapses are crucial for brain function, but the mechanisms underlying
      inhibitory synaptogenesis are unclear. Here, we show that postnatal Purkinje
      cells (PCs) of GABA(A)alpha1 knockout (KO) mice express transiently the alpha3
      subunit, leading to the assembly of functional GABA(A) receptors and initial
      normal formation of inhibitory synapses, that are retained until adulthood.
      Subsequently, down-regulation of the alpha3 subunit causes a complete loss of
      GABAergic postsynaptic currents, resulting in a decreased rate of inhibitory
      synaptogenesis and formation of mismatched synapses between GABAergic axons and
      PC spines. Notably, the postsynaptic adhesion molecule neuroligin-2 (NL2) is
      correctly targeted to inhibitory synapses lacking GABA(A) receptors and the
      scaffold molecule gephyrin, but is absent from mismatched synapses, despite
      innervation by GABAergic axons. Our data indicate that GABA(A) receptors are
      dispensable for synapse formation and maintenance and for targeting NL2 to
      inhibitory synapses. However, GABAergic signaling appears to be crucial for
      activity-dependent regulation of synapse density during neuronal maturation.

PMID- 18723688
TI  - A ketoreductase domain in the PksJ protein of the bacillaene assembly line
      carries out both alpha- and beta-ketone reduction during chain growth.
AB  - The polyketide signaling metabolites bacillaene and dihydrobacillaene are
      biosynthesized in Bacillus subtilis on an enzymatic assembly line with both
      nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) modules
      acting along with catalytic domains servicing the assembly line in trans. These
      signaling metabolites possess the unusual starter unit alpha-hydroxyisocaproate
      (alpha-HIC). We show here that it arises from initial activation of alpha
      ketoisocaproate (alpha-KIC) by the first adenylation domain of PksJ (a hybrid
      PKS/NRPS) and installation on the pantetheinyl arm of the adjacent thiolation (T)
      domain. The alpha-KIC unit is elongated to alpha-KIC-Gly by the second NRPS
      module in PksJ as demonstrated by mass spectrometric analysis. The third module
      of PksJ uses PKS logic and contains an embedded ketoreductase (KR) domain along
      with two adjacent T domains. We show that this KR domain reduces canonical 3
      ketobutyryl chains but also the alpha-keto group of alpha-KIC-containing
      intermediates on the PksJ T-domain doublet. This KR activity accounts for the
      alpha-HIC moiety found in the dihydrobacillaene/bacillaene pair and represents an
      example of an assembly-line dual-function alpha- and beta-KR acting on disparate
      positions of a growing chain intermediate.

PMID- 18723689
TI  - Nucleosome positioning in human HOX gene clusters.
AB  - The distribution of nucleosomes along the genome is a significant aspect of
      chromatin structure and is thought to influence gene regulation through
      modulation of DNA accessibility. However, properties of nucleosome organization
      remain poorly understood, particularly in mammalian genomes. Toward this goal we
      used tiled microarrays to identify stable nucleosome positions along the HOX gene
      clusters in human cell lines. We show that nucleosome positions exhibit sequence
      properties and long-range organization that are different from those
      characterized in other organisms. Despite overall variability of internucleosome
      distances, specific loci contain regular nucleosomal arrays with 195-bp
      periodicity. Moreover, such arrays tend to occur preferentially toward the 3'
      ends of genes. Through comparison of different cell lines, we find that active
      transcription is correlated with increased positioning of nucleosomes, suggesting
      an unexpected role for transcription in the establishment of well-positioned
      nucleosomes.

PMID- 18723690
TI  - Degeneration of dystrophic or injured skeletal muscles induces high expression of
      Galectin-1.
AB  - Muscle degenerative diseases such as Duchenne Muscular Dystrophy are incurable
      and treatment options are still restrained. Understanding the mechanisms and
      factors responsible for muscle degeneration and regeneration will facilitate the
      development of novel therapeutics. Several recent studies have demonstrated that
      Galectin-1 (Gal-1), a carbohydrate-binding protein, induces myoblast
      differentiation and fusion in vitro, suggesting a potential role for this
      mammalian lectin in muscle regenerative processes in vivo. However, the
      expression and localization of Gal-1 in vivo during muscle injury and repair are
      unclear. We report the expression and localization of Gal-1 during degenerative
      regenerative processes in vivo using two models of muscular dystrophy and muscle
      injury. Gal-1 expression increased significantly during muscle degeneration in
      the murine mdx and in the canine Golden Retriever Muscular Dystrophy animal
      models. Compulsory exercise of mdx mouse, which intensifies degeneration, also
      resulted in sustained Gal-1 levels. Furthermore, muscle injury of wild-type
      C57BL/6 mice, induced by BaCl(2) treatment, also resulted in a marked increase in
      Gal-1 levels. Increased Gal-1 levels appeared to localize both inside and outside
      the muscle fibers with significant extracellular Gal-1 colocalized with
      infiltrating CD45(+) leukocytes. By contrast, regenerating muscle tissue showed a
      marked decrease in Gal-1 to baseline levels. These results demonstrate
      significant regulation of Gal-1 expression in vivo and suggest a potential role
      for Gal-1 in muscle homeostasis and repair.

PMID- 18723691
TI  - The mycobacterial glycopeptidolipids: structure, function, and their role in
      pathogenesis.
AB  - Glycopeptidolipids (GPLs) are a class of glycolipids produced by several
      nontuberculosis-causing members of the Mycobacterium genus including pathogenic
      and nonpathogenic species. GPLs are expressed in different forms with production
      of highly antigenic, typeable serovar-specific GPLs in members of the
      Mycobacterium avium complex (MAC). M. avium and M. intracellulare, which comprise
      this complex, are slow-growing mycobacteria noted for producing disseminated
      infections in AIDS patients and pulmonary infections in non-AIDS patients.
      Previous studies have defined the gene cluster responsible for GPL biosynthesis
      and more recent work has characterized the function of the individual genes.
      Current research has also focused on the GPL's role in colony morphology, sliding
      motility, biofilm formation, immune modulation and virulence. These topics, along
      with new information on the enzymes involved in GPL biosynthesis, are the subject
      of this review.

PMID- 18723692
TI  - Plasmin therapy enhances mobilization of HPCs after G-CSF.
AB  - The role of proteinases in the mobilization of hematopoietic progenitor cells
      (HPCs) after granulocyte colony-stimulating factor (G-CSF) remains unclear. Here
      we report that genetic loss of the plasminogen activator inhibitor Pai-1 or of
      the plasmin inhibitor alpha2-antiplasmin increases HPC mobilization in response
      to G-CSF. Moreover, thrombolytic agents, such as tenecteplase and microplasmin,
      enhance HPC mobilization in mice and humans. Taken together, these findings
      identify a novel role for plasmin in augmenting HPC mobilization in response to G
      CSF.

PMID- 18723693
TI  - Targeted deletion of alpha-adducin results in absent beta- and gamma-adducin,
      compensated hemolytic anemia, and lethal hydrocephalus in mice.
AB  - In the red blood cell (RBC), adducin is present primarily as tetramers of alpha-
      and beta-subunits at spectrin-actin junctions, or junctional complexes. Mouse
      RBCs also contain small amounts of gamma-adducin. Platelets contain alpha- and
      gamma-adducin only. Adducin functions as a barbed-end actin capping protein to
      regulate actin filament length and recruits spectrin to the ends of actin
      filaments. To further define adducin's role in vivo, we generated alpha-adducin
      knockout mice. alpha-Adducin is absent in all tissues examined in homozygous null
      mice. In RBCs, beta- and gamma-adducin are also absent, indicating that alpha
      adducin is the limiting subunit in tetramer formation at the spectrin-actin
      junction. Similarly, gamma-adducin is absent in alpha-null platelets. alpha
      Adducin-null mice display compensated hemolytic anemia with features
      characteristic of RBCs in hereditary spherocytosis (HS), including spherocytes
      with significant loss of surface area, decreased mean corpuscular volume (MCV),
      cell dehydration, and increased osmotic fragility. Platelets maintain their
      normal discoid shape, and bleeding times are normal. alpha-Adducin-null mice show
      growth retardation at birth and throughout adulthood. Approximately 50% develop
      lethal communicating hydrocephalus with striking dilation of the lateral, third,
      and fourth ventricles. These data indicate that adducin plays a role in RBC
      membrane stability and in cerebrospinal fluid homeostasis.

PMID- 18723694
TI  - Snrk-1 is involved in multiple steps of angioblast development and acts via notch
      signaling pathway in artery-vein specification in vertebrates.
AB  - In vertebrates, molecular mechanisms dictate angioblasts' migration and
      subsequent differentiation into arteries and veins. In this study, we used a
      microarray screen to identify a novel member of the sucrose nonfermenting related
      kinase (snrk-1) family of serine/threonine kinases expressed specifically in the
      embryonic zebrafish vasculature and investigated its function in vivo. Using gain
      and loss-of-function studies in vivo, we show that Snrk-1 plays an essential
      role in the migration, maintenance, and differentiation of angioblasts. The
      kinase function of Snrk-1 is critical for migration and maintenance, but not for
      the differentiation of angioblasts. In vitro, snrk-1 knockdown endothelial cells
      show only defects in migration. The snrk-1 gene acts downstream or parallel to
      notch and upstream of gridlock during artery-vein specification, and the human
      gene compensates for zebrafish snrk-1 knockdown, suggesting evolutionary
      conservation of function.

PMID- 18723696
TI  - The clockwork ED.

PMID- 18723695
TI  - Differential contributions of dopamine and serotonin to orbitofrontal cortex
      function in the marmoset.
AB  - We have shown previously that the inhibitory control functions of the
      orbitofrontal cortex (OFC) are disrupted by serotonin, but not dopamine
      depletions. However, both dopamine and serotonin terminals and receptors are
      present within the OFC and thus the aim of the present study was to determine the
      differential contributions of these neurotransmitters to orbitofrontal function.
      OFC and dopamine are involved in the process by which neutral stimuli take on
      reinforcing properties, by virtue of their prior association with reward, and
      guide behavior. Thus, we compared the performance of marmosets with dopaminergic
      or serotoninergic OFC depletions on a test of conditioned reinforcement. To
      further our understanding of serotonin in behavioral flexibility, the effect of
      these depletions was also compared on the extinction of a visual discrimination.
      Monkeys with serotonin depletions of the OFC displayed stimulus-bound responding
      on both tests of conditioned reinforcement and discrimination extinction
      suggesting that orbitofrontal serotonin plays a specific role in preventing
      competing, task irrelevant, salient stimuli from biasing responding. In contrast,
      monkeys with dopamine depletion were insensitive to conditioned reinforcers and
      displayed persistent responding in the absence of reward in extinction, a pattern
      of deficits that may reflect basic deficits in the associative processing of
      reward.

PMID- 18723697
TI  - Use of helium-oxygen mixtures in the treatment of croup: a systematic review.
AB  - OBJECTIVE: To determine the effect of helium-oxygen inhalation on relieving
      symptoms and distress in children with croup as measured by the croup score, and
      to identify areas of uncertainty for future research. METHODS: Systematic review
      of prospective randomised and non-randomised controlled trials of children with
      the clinical diagnosis of croup, comparing the effect of helium-oxygen mixtures
      with placebo or any active treatment. Outcome measures were change in croup
      score, physiological parameters, hospital admission rates, need for intubation
      and adverse events. All records as identified by a systematic search strategy
      were assessed independently by two reviewers. RESULTS: Two trials were identified
      for inclusion assessing the effect of helium-oxygen inhalation in children with
      croup in an emergency department. In one trial the control group received
      humidified oxygen and in the other nebulised epinephrine. An improvement in the
      mean croup score over time was seen in the control and intervention groups of
      both trials, with no significant difference between the groups. Significant
      methodological and clinical heterogeneity in the design of the trials precluded a
      meaningful meta-analysis. CONCLUSION: At present there is no evidence to support
      the use of helium-oxygen therapy in children with croup. Methodologically well
      designed and adequately powered randomised controlled trials are needed to
      determine whether helium-oxygen inhalation as part of the initial treatment in
      croup alters outcome.

PMID- 18723699
TI  - Observational pain assessment versus self-report in paediatric triage.
AB  - OBJECTIVE: To examine if observational pain assessment can be used for purposes
      of triage in children aged >3 years. METHODS: A prospective, single blind,
      controlled trial was undertaken in children who presented to the emergency
      department (ED) with pain. Pain was assessed in the waiting room and again at
      triage before any treatment was administered using the Alder Hey Triage Pain
      Score (AHTPS), an observational tool designed for triage, and a self-report tool,
      either the Wong-Baker Faces Pain Rating Scale (WBS) for 3-7-year-old children or
      a visual analogue scale (VAS) for 8-15-year-old children. Scores were compared by
      instrument (observational and self-report) and ED location (waiting room and
      triage room). RESULTS: 75 children (29 aged 3-7 years and 46 aged 8-15 years)
      were enrolled in the study. The AHTPS scores were significantly lower than the
      scores measured by the WBS/VAS (p<0.001). The level of pain measured by both
      methods (self-report, observational) was lower in the triage room. Compared with
      the AHTPS, the WBS and VAS scored significantly lower in the triage room than in
      the waiting room (p<0.042 and p<0.006, respectively). CONCLUSIONS: Observational
      pain assessment underestimates children's perception of pain and should not be
      recommended in children aged >3 years. Triage has a calming effect on children.

PMID- 18723700
TI  - Hospital admissions with head injury following publication of NICE guidance.
AB  - BACKGROUND: A recent update suggested that the National Institute for Health and
      Clinical Excellence (NICE) guidance on head injury had led to safe early
      discharge, evidence of a reduction in the numbers of admitted patients and cost
      savings in some centres. The aim of this study was to use national Hospital
      Episodes Statistics (HES) data to determine whether admissions with head injury
      have changed since the NICE guidance was introduced. METHODS: HES data coded as
      S00-S09 "Injuries to the head" from 1998-9 to 2006-7 were examined for
      admissions, age and length of stay. RESULTS: Admissions rates did not change
      markedly until 2003 when the NICE head injury guidelines were issued. From 2003,
      admissions increased for all adult age groups but not for children. Mean length
      of stay remained constant between 1998 and 2007, so bed days increased in
      proportion to admission rates. CONCLUSION: Adult head injury admissions in
      England have increased markedly since the introduction of the NICE guidelines.
      Given that there is little evidence that hospital admission is beneficial for
      patients with minor head injury, NICE head injury guidance appears to have failed
      to promote cost effective care.

PMID- 18723701
TI  - Scant justification for interhospital transfers: a cause of reduced efficiency in
      the emergency department.
AB  - INTRODUCTION: Interhospital transfers are one of the critical points of the
      emergency system, which often cause overcrowding of the emergency department (ED)
      and limit its effectiveness. METHODS: A retrospective study was carried out,
      analyzing the clinical case files concerning the ED of the Policlinico "Umberto
      I" in Rome (Latium region, Italy) with the aim of establishing the reasons for
      the numerous unjustified transfers. RESULTS: From 1 January to 30 June 2006, 77
      597 admissions to the ED occurred, and 861 patients (1.1%) were sent from other
      hospitals. 361 patients out of 861 (41.9%) were transferred with critical
      clinical conditions. The remaining 500 patients (58.1%) were transferred
      requiring specialised care. The need for specialised care was confirmed in 230
      cases (46.0%) and therefore these transfers could be considered justified. The
      other 270 transfers (54.0%) were unjustified: 138 patients remained in the
      hospital to which they had been sent, contributing to crowding of the ED; 132
      patients were returned, thereby placing them at additional risk. CONCLUSION:
      Unfamiliarity with the regulations governing interhospital transfers is the main
      cause of scantly justified transfers and the consequent reduction in efficiency
      of the ED in the receiving hospital.

PMID- 18723702
TI  - Mass casualty incidents: are NHS staff prepared? An audit of one NHS foundation
      trust.
AB  - BACKGROUND: Lack of knowledge of an NHS trust's major incident policies by
      clinical staff may result in poorly coordinated responses during a mass casualty
      incident (MCI). AIM: To audit knowledge of the major incident policy by clinical
      staff working in a central London major acute NHS trust designated to receive
      casualties on a 24-h basis during a MCI. METHODS: A 12-question proforma was
      distributed to 307 nursing and medical staff in the hospital, designed to assess
      their knowledge of the major incident policy. Completed proformas were collected
      over a 2-month period between December 2006 and February 2007. RESULTS: A reply
      rate of 34% was obtained, with a reasonable representation from all disciplines
      ranging from nurses to consultants. Despite only 41% having read the policy in
      full, 70% knew the correct immediate action to take if informed of major incident
      activation. 76% knew the correct stand-down procedure. 56% knew the correct
      reporting point but less than 25% knew that an action card system was utilised.
      Nurses had significantly (p<0.01) more awareness of the policy than doctors.
      CONCLUSION: In view of the heightened terrorist threat in London, knowledge of
      major incident policy is essential. The high percentage of positive responses
      relating to immediate and stand-down actions reflects the rolling trust-wide MCI
      education programme and the organisational memory of the trust following several
      previous MCI in the capital. There is still scope for an improvement in
      awareness, however, particularly concerning knowledge of action cards, which are
      now displayed routinely throughout clinical areas and will be incorporated into
      induction packs.

PMID- 18723703
TI  - Epidemiology of mandibular fractures in a tertiary trauma centre.
AB  - BACKGROUND: Fractures of the mandible are common facial injuries. Patients
      frequently require hospitalisation, surgical intervention and extended periods of
      convalescence. METHODS: A prospective database of patients presenting to the Oral
      and Maxillofacial Surgery service at Christchurch Hospital during an 11-year
      period was reviewed. 1045 patients with mandibular fractures were identified.
      Variables examined included demographic data, type of fractures, mode of injury
      and treatment delivered. RESULTS: More than 90% of patients were men, with 64% in
      the 15-29 years age group. Interpersonal violence accounted for 49% of fractures,
      followed by sports (16%), falls (13%) and motor vehicle accidents (10%). The
      condyle was the most frequent fracture site (34%) and multiple fractures were
      seen in 37% of patients. Hospitalisation was required for 53% of patients with
      89% of these treatments being open reduction and internal fixation. CONCLUSION:
      Mandibular fracture is a common facial injury. The incidence is highest in young
      men who are victims of interpersonal violence. Alcohol is a major contributing
      factor. Management involved hospitalisation and surgical intervention for more
      than half of those presenting.

PMID- 18723704
TI  - Benefits of CT urography in patients presenting to the emergency department with
      suspected ureteric colic.
AB  - BACKGROUND: Ureteric colic is a common presentation in the emergency department
      and accounts for approximately 1% of all hospital admissions. Diagnosis depends
      on a typical history, clinical examination and the presence of haematuria.
      Intravenous urography has traditionally been used as the means of investigation,
      but over recent years this has been superseded by CT urography. This latter
      investigation gives potentially more information and may detect alternative or
      additional pathology which would otherwise be missed on intravenous urography.
      METHODS: 100 consecutive patients attending the emergency department with a
      provisional diagnosis of ureteric colic undergoing CT urography were studied to
      detect the incidence of alternative or incidental pathology. RESULTS: Stone
      disease was found in 58% of patients, with obstruction present in 43%. The most
      common site of obstruction was the vesicoureteric junction. Significant
      incidental or alternative pathology was found in 16% of patients. It was
      estimated that, in 12%, these findings would not have been detected by
      intravenous urography. CONCLUSION: The use of non-contrast CT urography is
      recommended in the initial investigation of patients with ureteric colic.

PMID- 18723705
TI  - "Heely"-related injuries in children.
AB  - BACKGROUND: "Heelys", or shoes with an integral wheel embedded into the heel, are
      becoming increasingly popular among children in the UK. Despite the
      manufacturer's claims about their safety, increasing numbers of patients are
      attending the emergency department with "Heely"-related injuries. AIM: To assess
      the number and type of "Heely"-related injuries seen in the emergency department
      in a busy district general hospital and to assess the number of school days lost
      as a result of these injuries as a secondary measure of the impact on education
      and lifestyle. METHOD: Medical staff working in the emergency department
      completed proformas for all children attending the department with "Heely"
      related injuries between 26 December and 26 April 2007. Data collected included
      age, sex, mechanism of injury, diagnosis and number of days off school as a
      result of the injury. RESULTS: 35 patients with "Heely"-related injuries of mean
      age 9.6 years (range 6-15) were identified during the study period. The most
      common mechanism of injury was a fall onto an outstretched hand (20/35, 57%).
      Other mechanisms of injury identified were lateral upper limb injury (7/35),
      traumatic lower limb injury (2/35), rotational lower limb injury (2/35), head
      injury (2/35) and back injury (2/35). The most common diagnosis was fracture of
      the distal radius (10/35), two of which had an associated distal ulna fracture.
      Two tibial fractures and one nasal fracture were also seen. The average number of
      days off school was 4.5 days (range 0-20). None of the children included in this
      study were using safety equipment at the time of the injury. CONCLUSIONS: The
      number of "Heely"-related injuries seen in one department over a 4-month period
      suggests a much higher incidence of injuries than the 46/100,000 found by the
      manufacturers based on Consumer Product Safety Commission data in the USA. The
      discrepancy is almost certainly due to the reluctance of UK children to use
      safety equipment and to follow the manufacturer's safety advice. Larger scale
      studies are needed to confirm the incidence of "Heely"-related injuries in
      emergency departments across the UK. If the high incidence of injuries among
      users is confirmed, primary and secondary prevention methods could be considered
      to reduce injuries.

PMID- 18723706
TI  - Can a change in policy reduce emergency hospital admissions? Effect of admission
      avoidance team, guideline implementation and maximising the observation unit.
AB  - BACKGROUND: Reduction in admissions is an important aim of emergency department
      working policy to overcome the problems of a shortage of inpatient beds,
      overcrowding, rising costs and exhausted resources. A new policy was instituted
      in the emergency department of a hospital in Kuwait with the following
      components: (1) an admission avoidance team of emergency department doctors; (2)
      implementation of disease management guidelines; and (3) maximising the use of an
      emergency department observation unit. METHODS: The effects of this policy on
      reduction in admission rates for total medical admissions and for chest pain,
      bronchial asthma, heart failure, pneumonia and pyelonephritis as selected samples
      of common medical conditions were prospectively studied over a period of 3 years
      from institution of the policy and compared with the 3-year period before the
      policy was instituted. RESULTS: There was a significant reduction in admission
      rates after institution of the new policy, with a relative reduction of 35.9% for
      total medical admissions, 52.7% for chest pain, 49.2% for bronchial asthma, 34.7%
      for heart failure, 59.1% for pneumonia and 43.3% for pyelonephritis compared with
      the period before the policy was instituted. CONCLUSION: A multidisciplinary
      emergency department policy, using as much available evidence as possible, was
      successful in significantly reducing medical hospital admissions in spite of the
      rising numbers of patients visiting the emergency department and observation
      unit.

PMID- 18723707
TI  - Audit of the safety and effectiveness of ketamine for procedural sedation in the
      emergency department.
AB  - AIM: To examine the effectiveness and safety of the sedative agents used in the
      emergency department following the introduction of ketamine as an agent for
      procedural sedation METHODS: A 2-year prospective audit of sedation practice was
      undertaken. This specifically examined the rationale behind a doctor's choice of
      sedative agent, the depth of sedation achieved, adverse events and the time taken
      to regain full orientation. RESULTS: 210 patients were included of whom 85 (40%)
      were given ketamine, 107 (51%) midazolam and 18 (9%) propofol. The median time to
      full orientation was 25 min for ketamine, 30 min for midazolam and 10 min for
      propofol. Complications occurred in 15.9% of sedations overall (14.6% of those
      given ketamine, 15.8% given midazolam and 22.2% given propofol). Apnoea and
      hypoxia most often occurred with midazolam and propofol, while hypertension and
      hypertonicity were encountered more frequently with ketamine. In addition, 19.5%
      of patients given ketamine suffered the re-emergence phenomenon. The association
      between deep sedation with no response to pain and adverse events encountered
      with midazolam does not occur with ketamine. CONCLUSIONS: Ketamine is both safe
      and effective and compares favourably with midazolam as an agent for procedural
      sedation in the emergency department. Although the re-emergence phenomenon
      occurred, no psychological sequelae were encountered after return to full
      orientation. Ketamine may be particularly useful in groups of patients at high
      risk of adverse effects with midazolam.

PMID- 18723708
TI  - Serum adenosine deaminase levels in diagnosis of acute appendicitis.
AB  - BACKGROUND: Adenosine deaminase (ADA) is found in most tissues including lymphoid
      cells and lymph nodes. It is a marker of T lymphocyte activation. The role of
      type 1 and type 2 T helper cells in appendicitis has been investigated
      experimentally. Serum ADA levels in acute appendicitis have not previously been
      studied. AIM: To assess the serum levels of ADA in patients with acute
      appendicitis. METHODS: Serum levels of ADA were investigated in 30 cases with
      acute appendicitis (mean age 26 years; male/female 17/13) and 21 healthy controls
      (mean age 40 years; male/female 11/10). Levels of ADA were compared in patients
      with acute appendicitis and healthy controls. Correlation analysis between ADA
      and other inflammatory markers (C-reactive protein (CRP), high-sensitivity CRP,
      erythrocyte sedimentation rate and white blood cell count) was also performed.
      RESULTS: Mean (SD) serum ADA levels were significantly higher in those with acute
      appendicitis than in the control group (13.41 (3.56) U/l vs 9.39 (1.22) U/l;
      p<0.001). There was no correlation between ADA and the other inflammatory markers
      investigated. CONCLUSIONS: Although serum levels of ADA do not correlate with
      other known inflammatory markers, its serum level is increased in acute
      appendicitis and it has a higher positive predictive value.

PMID- 18723709
TI  - Morphine analgesia in patients with acute appendicitis: a randomised double-blind
      clinical trial.
AB  - BACKGROUND: The administration of analgesics to patients with acute abdominal
      pain due to acute appendicitis is controversial. A study was undertaken to assess
      the analgesic effect of morphine in patients with acute appendicitis. METHODS: A
      randomised double-blind clinical trial was conducted in Sina hospital, a general
      teaching hospital, from January 2004 to March 2005. Patients scheduled for
      appendectomy were randomised to receive 0.1 mg/kg morphine sulfate or saline
      (0.9%) to a maximum dose of 10 mg over a 5 min period. Patients were examined by
      surgeons not involved in their care before and after drug administration and
      their pain intensity and signs were recorded at each visit. The physicians were
      also asked to indicate their own treatment plan. The main outcome measures were
      pain intensity using a visual analogue scale (VAS) and signs of acute
      appendicitis. A favourable reduction in VAS score was defined as a change of >13
      mm. RESULTS: Of the 71 patients enrolled in the study, 35 were allocated to
      receive morphine and 36 to receive placebo. One patient left the hospital before
      receiving morphine. No significant differences were seen between the two groups
      with regard to age, sex and initial VAS score. A more favourable change in VAS
      score was reported in the morphine group with a significantly greater reduction
      in the median VAS score than in the placebo group. Morphine administration did
      not cause significant changes in patients' signs or in the physicians' plans or
      diagnoses. No adverse events were seen in either group. CONCLUSION: Morphine can
      reduce pain in patients with acute appendicitis without affecting diagnostic
      accuracy. TRIAL REGISTRATION NUMBER: NCT00477061.

PMID- 18723710
TI  - Critical appraisal for emergency medicine 3: evaluation of a therapy.

PMID- 18723711
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Bet 1. Lactate clearance a better predictor of mortality than initial
      lactate level.

PMID- 18723713
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Bet 2. Steroids in children with erythema multiforme.

PMID- 18723714
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Bet 3. Chest physiotherapy is not useful in bronchiolitis.

PMID- 18723715
TI  - Performance of cellular phones with video telephony in the use of automated
      external defibrillators by untrained laypersons.
AB  - AIM: To evaluate the hypothesis that using an automated external defibrillator
      (AED) with video telephony-directed cellular phone instructions for untrained
      laypersons would increase the probability of successful performance of AEDs. Real
      time communication with visual images can provide critical information and
      appropriate instructions to both laypersons and dispatchers. METHODS: A
      prospective observational study was undertaken. 52 public officers with no
      previous experience in the use of a defibrillator were presented with a scenario
      in which they were asked to use an AED on a manikin according to the instructions
      given to them by cellular phones with video telephony. The proportion who
      successfully delivered a shock and the time interval from cardiac arrest to
      delivery of the shock were recorded. RESULTS: Placement of the electrode pads was
      performed correctly by all 52 participants and 51 (98%) delivered an accurate
      shock. The mean (SD) time to correct shock delivery was 131.8 (20.6) s (range 101
      202). CONCLUSION: Correct pad placement and shock delivery can be performed using
      an AED when instructions are provided via video telephone because a dispatcher
      can monitor every step and provide correct information.

PMID- 18723716
TI  - AMPDS categories: are they an appropriate method to select cases for extended
      role ambulance practitioners?
AB  - OBJECTIVES: To examine the correlation between the AMPDS prioritisation category
      at dispatch and the use of alternative clinical dispatch using data from an
      emergency care practitioner (ECP) service dispatching on likely clinical need.
      METHODS: Data for a 12-month period were reviewed for all 999 calls seen by an
      ECP and comparison was made between AMPDS code/category and outcome of the
      patient. RESULTS: 3955 cases were reviewed with all but two AMPDS code groups
      represented. All categories showed alternative pathways to the emergency
      department used by ECPs: category A, 36%; category B, 52%; category C, 44%.
      CONCLUSIONS: Clinically directed dispatch for ECPs allows utilisation of
      alternative pathways across all AMPDS categories, suggesting that AMPDS alone is
      not a good predictor of potential for avoiding emergency department attendance
      and possible hospital admission.

PMID- 18723717
TI  - Use of the pneumatic anti-shock garment.

PMID- 18723718
TI  - Phantom tumour of the lung.

PMID- 18723720
TI  - Meningitis in a butcher.
AB  - Streptococcus suis is a common pathogen in swine and infection in humans is
      rarely reported. When it does occur, it is considered an occupational risk
      associated with the handling of carcasses. Meningitis is one of the most life
      threatening manifestations of S suis infection. This case of meningitis in a
      butcher is reported to create awareness of this zoonotic disease. The report
      highlights the importance of an occupational history and a meticulous general
      physical examination looking for cuts and abrasions in patients with suspicion of
      meningitis.

PMID- 18723721
TI  - Massive abdominal wall haematoma and haemothorax due to spontaneous rupture of an
      intercostal artery.

PMID- 18723722
TI  - Neck pain and minor trauma: normal radiographs do not always exclude serious
      pathology.
AB  - A 37-year-old woman presented following a trampolining accident with neck pain
      and paraesthesia of the left arm. Cervical spine radiographs were normal and a
      provisional diagnosis of whiplash was made. Three hours later she developed
      rotational vertigo and then cerebellar signs. Magnetic resonance angiography and
      magnetic resonance imaging of the brain confirmed the diagnosis of vertebral
      artery dissection (VAD) with cerebellar embolic infarcts. She was anticoagulated
      and symptoms resolved over one week. VAD is a relatively common cause of
      posterior circulation stroke in young people. It usually presents following
      (often minor) trauma, with headache, neck pain, cerebellar, sensory and cranial
      nerve signs. However, it remains a diagnosis that is frequently missed or
      misdiagnosed.

PMID- 18723723
TI  - Atropine-resistant bradycardia due to hyperkalaemia.
AB  - Symptomatic sinus bradycardia is routinely treated in the emergency department
      with atropine and pacing. Two cases are presented that illustrate the importance
      of considering hyperkalaemia, particularly in the presence of atropine-resistant
      symptomatic bradycardia. The administration of calcium in such cases acts to
      stabilise the myocardium and resolve the bradycardia. Blood gas analysis provides
      a rapid estimate of serum potassium concentrations, facilitating timely
      treatment.

PMID- 18723724
TI  - Hyperchloraemic metabolic acidosis.
AB  - Cholestyramine carries a risk of hyperchloraemic metabolic acidosis. Being
      cognisant of this drug-induced adverse event may reduce diagnostic delays.
      Emergency physicians should be alert about this condition, in particular among
      patients with pre-existing chronic kidney disease, or who are taking
      spironolactone.

PMID- 18723725
TI  - Brachial plexus trauma: the morbidity of hemidiaphragmatic paralysis.
AB  - Phrenic nerve palsy has previously been associated with brachial plexus root
      avulsion; severe unilateral phrenic nerve injury is not uncommonly associated
      with brachial plexus injury. Brachial plexus injuries can be traumatic (gunshot
      wounds, lacerations, stretch/contusion and avulsion injuries) or non-traumatic in
      aetiology (supraclavicular brachial plexus nerve block, subclavian vein
      catheterisation, cardiac surgeries, or obstetric complications such as birth
      palsy). Despite the known association, the incidence and morbidity of a phrenic
      nerve injury and hemidiaphragmatic paralysis associated with traumatic brachial
      plexus stretch injuries remains ill-defined. The incidence of an associated
      phrenic nerve injury with brachial plexus trauma ranges from 10% to 20%; however,
      because unilateral diaphragmatic paralysis often presents without symptoms at
      rest, a high number of phrenic nerve injuries are likely to be overlooked in the
      setting of brachial plexus injury. A case report is presented of a unilateral
      phrenic nerve injury associated with brachial plexus stretch injury presenting
      with a recalcitrant left lower lobe pneumonia.

PMID- 18723728
TI  - Demographics of workplace violence: methodology is the key.

PMID- 18723729
TI  - Ketamine use in prehospital critical care.

PMID- 18723731
TI  - The importance of journey times to hospital in urban areas.

PMID- 18723732
TI  - Gut contamination of acutely poisoned patients: why is no one using the NICE
      guideline?

PMID- 18723736
TI  - Administering a glyceryl trinitrate infusion: faster is better than slower.

PMID- 18723739
TI  - Prophylactic laser photocoagulation for acute retinal necrosis. Does it raise
      more questions than answers?

PMID- 18723740
TI  - Anatomical eye model.

PMID- 18723741
TI  - Donor dislocation after DSAEK for a failed corneal graft.

PMID- 18723742
TI  - Visual impairment due to undiagnosed refractive error in working age adults in
      Britain.
AB  - BACKGROUND: Detection and treatment of undiagnosed refractive error (RE), with
      its attendant functional consequences, is a priority of VISION 2020, the global
      initiative against avoidable visual disability. The authors investigated the
      frequency of visual impairment due to undiagnosed RE and its associations with
      vision-related quality of life (VRQOL), general health and social circumstances
      in a contemporary and nationally representative population of British working-age
      adults. METHODS: 9271 members of the 1958 British birth cohort had visual acuity
      and VRQOL assessed at 44/45 years. The authors compared those with undiagnosed RE
      with those with diagnosed RE, defining undiagnosed RE as >or=0.2 logMAR units/2
      lines acuity improvement in both eyes with pinhole in individuals without current
      or prior optical treatment or ophthalmic history. RESULTS: 144/9271 (1.6%)
      individuals had undiagnosed and 3513/9271 (37.9%) diagnosed RE. 18% (24/144) of
      those with undiagnosed RE were classifiable as visually impaired. Individuals
      with undiagnosed RE were more likely to have a manual (vs non-manual) occupation
      and to be separated, divorced or widowed, and less likely to be in social or
      professional organisations. There is also some evidence that they are more likely
      to express concern, embarrassment and frustration about their eyesight and worry
      about coping with life. CONCLUSION: A significant proportion of working age
      adults in Britain appear to have undiagnosed but visually significant RE.
      Improvements in existing opportunities for detecting RE in adults could benefit
      these individuals during their working lives and avoid the serious adverse
      consequences associated with vision impairment in later life.

PMID- 18723743
TI  - The additional yield of a periodic screening programme for open-angle glaucoma: a
      population-based comparison of incident glaucoma cases detected in regular
      ophthalmic care with cases detected during screening.
AB  - AIM: To study the additional yield of a periodic screening programme for open
      angle glaucoma (OAG) by comparing, in a population-based setting, incident OAG
      (iOAG) cases detected in regular ophthalmic care with those detected during
      screening. METHODS: Participants aged 55 and over from the population-based
      Rotterdam Study underwent the same ophthalmic examination at baseline (1991-3)
      and follow-up (1997-9), including visual field testing and simultaneous stereo
      optic disc photography. Of 3842 participants, 87 (2.3%) developed iOAG during a
      mean follow-up time of 6.5 years. Of these 87 iOAG cases, 78 (90%) were included
      in this study. RESULTS: Of the 78 iOAG cases detected at follow-up, 23 (29%) had
      already been detected before during regular ophthalmic care. The remaining 55
      (71%) undetected iOAG cases more often showed glaucomatous optic neuropathy
      without glaucomatous visual field loss (29 of 55 (53%)) as compared with the
      detected cases (four of 23 (17%); p = 0.009). Of the undetected iOAG cases, only
      four had developed significant visual field loss in their better eye. CONCLUSION:
      The additional yield of a periodic OAG screening programme is lower than expected
      from published prevalence data. In the discussion, the authors estimate that-in a
      white population with a low prevalence of pseudoexfoliation-about one in 1000
      screened persons could be saved from bilateral end-stage OAG.

PMID- 18723744
TI  - Expression of glial cell-derived neurotrophic factor and its receptor in the stem
      cell-containing human limbal epithelium.
AB  - AIM: To evaluate the expression pattern of glial cell line-derived neurotrophic
      factor (GDNF) with its receptors GDNF family receptor alpha-1 (GFR alpha-1) and
      Ret in the human corneal and limbal tissues, as well as in the primary human
      limbal epithelial cultures (PHLEC). METHODS: Expression of GDNF and its
      receptors, and the co-localisation with stem cell associated and differentiation
      markers were evaluated by immunofluorescent staining, western blot analysis and
      real-time PCR in the fresh human corneoscleral tissues, as well as in the PHLEC.
      Single cell colony-forming and wound-healing assays were also evaluated in PHLEC.
      RESULTS: GDNF and GFR alpha-1 were found to be expressed by a subset of basal
      cells and co-localised with ATP-binding cassette, subfamily G (WHITE), member 2
      (ABCG2) and p63, but not with cytokeratin 3 in the human limbal basal epithelium.
      In PHLEC, they were expressed by a small population of cells in the less
      differentiated stage. The GDNF and GFR alpha-1-positive subpopulations were
      enriched for the expression of ABCG2 and p63 (p<0.01). Recombinant human GDNF
      promoted the proliferation and wound healing of epithelial cells in the PHLEC. In
      contrast, Ret was abundantly located in the human corneal epithelium except for
      the basal cells of the limbal epithelium. CONCLUSION: These findings indicate
      that GDNF and GFR alpha-1 may represent a property for the phenotype of human
      corneal epithelial precursor cells. GDNF may signal independently of Ret through
      GFR alpha-1 in the stem cell-containing limbal epithelium.

PMID- 18723746
TI  - In vitro amoebacidal activity of photodynamic therapy on Acanthamoeba.
AB  - AIM: To evaluate the effectiveness of Hypocrellins B (HB) photodynamic therapy
      (PDT) on Acanthamoeba trophozoites and cysts, and its cytotoxic potential on the
      corneal epithelial cells and stromal cells in vitro. METHODS: Acanthamoeba
      trophozoites and cysts (5 x 10(4)/ml) were incubated with various concentrations
      of HB, followed by exposure to light (>470 nm) for 30 min at a fluence rate of 50
      mW/cm(2). Survival rate was assessed using the live/dead viability/cytotoxicity
      assay and non-nutrient agar--Escherichia coli culture assay. Rabbit corneal
      epithelial cells and stromal cells were incubated with various concentrations of
      HB, followed by exposure to the same light fluence rate as above. The corneal
      cell survival rate was assessed using the live/dead viability/cytotoxicity assay.
      RESULTS: HB-PDT showed a dose-dependent inhibition on the trophozoites and cysts.
      The 100% inhibitory concentration (IC(100)) of HB was 1 microg/ml for the
      trophozoites and 20 microg/ml for the cysts. The 50% inhibitory concentration
      (IC(50)) of HB for the cysts was 3.8 microg/ml and for the trophozoites 0.23
      microg/ml. The inhibition of the HB-PDT on the rabbit corneal cells and stromal
      cells was observed, but HB without irradiation had no inhibition on the corneal
      cells. CONCLUSION: HB-PDT had amoebacidal properties in vitro and showed a better
      effectiveness on the trophozoites than the cysts. Meanwhile, HB-PDT demonstrated
      cytotoxicity on the corneal epithelial cells and stromal cells, but HB exhibited
      no appreciable cytotoxicity in the dark to the corneal cells.

PMID- 18723745
TI  - Conjunctival and corneal reactions in rabbits following short- and repeated
      exposure to preservative-free tafluprost, commercially available latanoprost and
      0.02% benzalkonium chloride.
AB  - AIM: To compare the conjunctival and corneal reactions of commercially available
      solution of latanoprost (Xalatan) and preservative-free (PF) tafluprost in
      rabbits. METHODS: The rabbits received 50 microl of phosphate-buffered saline
      (PBS), PF-tafluprost 0.0015%, latanoprost 0.005% or benzalkonium chloride (BAK)
      0.02%; all solutions were applied at 5 min intervals for a total of 15 times. The
      ocular surface toxicity was investigated using slit-lamp biomicroscopy
      examination, flow cytometry (FCM) and on imprints for CD45 and tumour necrosis
      factor-receptor 1 (TNFR1) conjunctival impression cytology (CIC) and corneal in
      vivo confocal microscopy (IVCM). Standard immunohistology also assessed
      inflammatory/apoptotic cells. RESULTS: Clinical observation and IVCM images
      showed the highest ocular surface toxicity with latanoprost and BAK, while PF
      tafluprost and PBS eyes presented almost normal corneoconjunctival aspects. FCM
      showed a higher expression of CD45+ and TNFR1+ in latanoprost- or BAK-instilled
      groups, compared with PF-tafluprost and PBS groups. Latanoprost induced fewer
      positive cells for inflammatory marker expressions in CIC specimens compared with
      BAK-alone, both of which were higher than with PF-tafluprost or PBS.
      Immunohistology showed the same tendency of toxic ranking. CONCLUSION: The
      authors confirm that rabbit corneoconjunctival surfaces presented a better
      tolerance when treated with PF-tafluprost compared with commercially available
      latanoprost or BAK solution.

PMID- 18723748
TI  - Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a
      new candidate gene for normal tension glaucoma.
AB  - AIMS: The aim of this study was to investigate the association between normal
      tension glaucoma and the candidate disease locus glaucoma 1, open angle, B
      (GLC1B) on chromosome 2. There are many reports describing the results of
      association or linkage studies for primary open angle glaucoma (POAG), with GLC1B
      as one of the loci associated with normal or moderately elevated intraocular
      pressure. However, there are few reports about the association of genes or
      defined genomic regions with normal tension glaucoma, which is the leading type
      of glaucoma in Japan. The GLC1B locus is hypothesized to be a causative region
      for normal tension glaucoma. METHODS: Genomic DNA was extracted from whole blood
      of normal tension glaucoma (n = 143) and healthy controls (n = 103) of Japanese
      origin. RESULTS: Fifteen microsatellite markers within and/or near to the GLC1B
      locus were genotyped, and their association with normal tension glaucoma was
      analysed. Two markers D2S2264 and D2S176 had significant positive associations.
      CONCLUSION: The D2S176 marker had the strongest significant association and it is
      located 24 kb from the nearest gene NCK2, which now becomes an important new
      candidate gene for future studies of its association with normal tension
      glaucoma.

PMID- 18723749
TI  - Histological determinant of mortality in retinoblastoma in Ibadan.

PMID- 18723750
TI  - How to treat recurrences after Avastin treatment for neovascular AMD: stick to
      Avastin or switch to Lucentis?

PMID- 18723751
TI  - Trabeculotomy for the treatment of glaucoma after Descemet stripping endothelial
      keratoplasty.

PMID- 18723753
TI  - Management of angle-closure glaucoma in East Asian eyes: a response to argon
      laser iridotomy-induced bullous keratopathy, a growing problem in Japan.

PMID- 18723755
TI  - Ocular blood flow and glaucoma.

PMID- 18723758
TI  - Generation of transgenic maize with enhanced provitamin A content.
AB  - Vitamin A deficiency (VAD) affects over 250 million people worldwide and is one
      of the most prevalent nutritional deficiencies in developing countries, resulting
      in significant socio-economic losses. Provitamin A carotenoids such as beta
      carotene, are derived from plant foods and are a major source of vitamin A for
      the majority of the world's population. Several years of intense research has
      resulted in the production of 'Golden Rice 2' which contains sufficiently high
      levels of provitamin A carotenoids to combat VAD. In this report, the focus is on
      the generation of transgenic maize with enhanced provitamin A content in their
      kernels. Overexpression of the bacterial genes crtB (for phytoene synthase) and
      crtI (for the four desaturation steps of the carotenoid pathway catalysed by
      phytoene desaturase and zeta-carotene desaturase in plants), under the control of
      a 'super gamma-zein promoter' for endosperm-specific expression, resulted in an
      increase of total carotenoids of up to 34-fold with a preferential accumulation
      of beta-carotene in the maize endosperm. The levels attained approach those
      estimated to have a significant impact on the nutritional status of target
      populations in developing countries. The high beta-carotene trait was found to be
      reproducible over at least four generations. Gene expression analyses suggest
      that increased accumulation of beta-carotene is due to an up-regulation of the
      endogenous lycopene beta-cylase. These experiments set the stage for the design
      of transgenic approaches to generate provitamin A-rich maize that will help
      alleviate VAD.

PMID- 18723759
TI  - Diabetes induces pulmonary artery endothelial dysfunction by NADPH oxidase
      induction.
AB  - Recent data suggest that diabetes is a risk factor for pulmonary hypertension.
      The aim of the present study was to analyze whether diabetes induces endothelial
      dysfunction in pulmonary arteries and the mechanisms involved. Male Sprague
      Dawley rats were randomly divided into a control (saline) and a diabetic group
      (70 mg/kg(-1) streptozotocin). After 6 wk, intrapulmonary arteries were mounted
      for isometric tension recording, and endothelial function was tested by the
      relaxant response to acetylcholine. Protein expression and localization were
      measured by Western blot and immunohistochemistry and superoxide production by
      dihydroethidium staining. Pulmonary arteries from diabetic rats showed impaired
      relaxant response to acetylcholine and reduced vasoconstrictor response to the
      nitric oxide (NO) synthase inhibitor L-NAME, whereas the response to
      nitroprusside and the expression of endothelial NO synthase remained unchanged.
      Endothelial dysfunction was reversed by addition of superoxide dismutase or the
      NADPH oxidase inhibitor apocynin. An increase in superoxide production and
      increased expression of the NADPH oxidase regulatory subunit p47(phox) were also
      found in pulmonary arteries from diabetic rats. In conclusion, the pulmonary
      circulation is a target for diabetes-induced endothelial dysfunction via enhanced
      NADPH oxidase-derived superoxide production.

PMID- 18723760
TI  - AICAR decreases the activity of two distinct amiloride-sensitive Na+-permeable
      channels in H441 human lung epithelial cell monolayers.
AB  - Transepithelial transport of Na(+) across the lung epithelium via amiloride
      sensitive Na(+) channels (ENaC) regulates fluid volume in the lung lumen.
      Activators of AMP-activated protein kinase (AMPK), the adenosine monophosphate
      mimetic AICAR, and the biguanide metformin decreased amiloride-sensitive apical
      Na(+) conductance (G(Na+)) in human H441 airway epithelial cell monolayers. Cell
      attached patch-clamp recordings identified two distinct constitutively active
      cation channels in the apical membrane that were likely to contribute to G(Na+):
      a 5-pS highly Na(+) selective ENaC-like channel (HSC) and an 18-pS nonselective
      cation channel (NSC). Substituting NaCl with NMDG-Cl in the patch pipette
      solution shifted the reversal potentials of HSC and NSC, respectively, from +23
      mV to -38 mV and 0 mV to -35 mV. Amiloride at 1 microM inhibited HSC activity and
      56% of short-circuit current (I(sc)), whereas 10 microM amiloride partially
      reduced NSC activity and inhibited a further 30% of I(sc). Neither conductance
      was associated with CNG channels as there was no effect of 10 microM pimoside on
      I(sc), HSC, or NSC activity, and 8-bromo-cGMP (0.3-0.1 mM) did not induce or
      increase HSC or NSC activity. Pretreatment of H441 monolayers with 2 mM AICAR
      inhibited HSC/NSC activity by 90%, and this effect was reversed by the AMPK
      inhibitor Compound C. All three ENaC proteins were identified in the apical
      membrane of H441 monolayers, but no change in their abundance was detected after
      treatment with AICAR. In conclusion, activation of AMPK with AICAR in H441 cell
      monolayers is associated with inhibition of two distinct amiloride-sensitive
      Na(+)-permeable channels by a mechanism that likely reduces channel open
      probability.

PMID- 18723761
TI  - Mice expressing BMPR2R899X transgene in smooth muscle develop pulmonary vascular
      lesions.
AB  - Familial pulmonary arterial hypertension (PAH) is associated with mutations in
      bone morphogenetic protein type II receptor (BMPR2). Many of these mutations
      occur in the BMPR2 tail domain, leaving the SMAD functions intact. To determine
      the in vivo consequences of BMPR2 tail domain mutation, we created a smooth
      muscle-specific doxycycline-inducible BMPR2 mutation with an arginine to
      termination mutation at amino acid 899. When these SM22-rtTA x TetO(7)
      BMPR2(R899X) mice had transgene induced for 9 wk, starting at 4 wk of age, they
      universally developed pulmonary vascular pruning as assessed by fluorescent
      microangiography. Approximately one-third of the time, the induced animals
      developed elevated right ventricular systolic pressures (RVSP), associated with
      extensive pruning, muscularization of small pulmonary vessels, and development of
      large structural pulmonary vascular changes. These lesions included large numbers
      of macrophages and T cells in their adventitial compartment as well as CD133
      positive cells in the lumen. Small vessels filled with CD45-positive and
      sometimes CD3-positive cells were a common feature in all SM22-rtTA x TetO(7)
      BMPR2(R899X) mice. Gene array experiments show changes in stress response, muscle
      organization and function, proliferation, and apoptosis and developmental
      pathways before RVSP increases. Our results show that the primary phenotypic
      result of BMPR2 tail domain mutation in smooth muscle is pulmonary vascular
      pruning leading to elevated RVSP, associated with early dysregulation in multiple
      pathways with clear relevance to PAH. This model should be useful to the research
      community in examining early molecular and physical events in the development of
      PAH and as a platform to validate potential treatments.

PMID- 18723762
TI  - Role played by acid-sensitive ion channels in evoking the exercise pressor
      reflex.
AB  - The exercise pressor reflex arises from contracting skeletal muscle and is
      believed to play a role in evoking the cardiovascular responses to static
      exercise, effects that include increases in arterial pressure and heart rate.
      This reflex is believed to be evoked by the metabolic and mechanical stimulation
      of thin fiber muscle afferents. Lactic acid is known to be an important metabolic
      stimulus evoking the reflex. Until recently, the only antagonist for acid
      sensitive ion channels (ASICs), the receptors to lactic acid, was amiloride, a
      substance that is also a potent antagonist for both epithelial sodium channels as
      well as voltage-gated sodium channels. Recently, a second compound, A-317567, has
      been shown to be an effective and selective antagonist to ASICs in vitro.
      Consequently, we measured the pressor responses to the static contraction of the
      triceps surae muscles in decerebrate cats before and after a popliteal arterial
      injection of A-317567 (10 mM solution; 0.5 ml). We found that this ASIC
      antagonist significantly attenuated by half (P<0.05) the pressor responses to
      both contraction and to lactic acid injection into the popliteal artery. In
      contrast, A-317567 had no effect on the pressor responses to tendon stretch, a
      pure mechanical stimulus, and to a popliteal arterial injection of capsaicin,
      which stimulated transient receptor potential vanilloid type 1 channels. We
      conclude that ASICs on thin fiber muscle afferents play a substantial role in
      evoking the metabolic component of the exercise pressor reflex.

PMID- 18723763
TI  - Formation and function of ceramide-enriched membrane platforms with CD38 during
      M1-receptor stimulation in bovine coronary arterial myocytes.
AB  - CD38 contains an ADP ribosylcyclase domain that mediates intracellular Ca(2+)
      signaling by the production of cyclic ADP-ribose (cADPR), but the mechanisms by
      which the agonists activate this enzyme remain unclear. The present study tested
      a hypothesis that a special lipid-raft (LR) form, ceramide-enriched lipid
      platform, contributes to CD38 activation to produce cADPR in response to
      muscarinic type 1 (M(1)) receptor stimulation in bovine coronary arterial
      myocytes (CAMs). By confocal microscopic analysis, oxotremorine (Oxo), an M(1)
      receptor agonist, was found to increase LR clustering on the membrane with the
      formation of a complex of CD38 and LR components such as GM(1), acid
      sphingomyelinase (ASMase), and ceramide, a typical ceramide-enriched macrodomain.
      At 80 microM, Oxo increased LR clustering by 78.8%, which was abolished by LR
      disruptors, methyl-beta-cyclodextrin (MCD), or filipin. With the use of a
      fluorescence resonance energy transfer (FRET) technique, 15.5+/-1.9% energy
      transfer rate (vs. 5.3+/-0.9% of control) between CD38 and LR component,
      ganglioside M(1) was detected, further confirming the proximity of both
      molecules. In the presence of MCD or filipin, there were no FRET signals
      detected. In floated detergent-resistant membrane fractions, CD38 significantly
      increased in LR fractions of CAMs treated by Oxo. Moreover, MCD or filipin
      attenuated Oxo-induced production of cADPR via CD38. Functionally, Oxo-induced
      intracellular Ca(2+) release and coronary artery constriction via cADPR were also
      blocked by LR disruption or ASMase inhibition. These results provide the first
      evidence that the formation of ceramide-enriched lipid macrodomains is crucial
      for Oxo-induced activation of CD38 to produce cADPR in CAMs, and these lipid
      macrodomains mediate transmembrane signaling of M(1) receptor activation to
      produce second messenger cADPR.

PMID- 18723764
TI  - Inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances
      alpha1D-adrenergic receptor constriction.
AB  - G protein-coupled receptor kinase 2 (GRK2) is a serine/theorinine kinase that
      phosphorylates and desensitizes agonist-bound G protein-coupled receptors. GRK2
      is increased in expression and activity in lymphocytes and vascular smooth muscle
      (VSM) in human hypertension and animal models of the disease. Inhibition of GRK2
      using the carboxyl-terminal portion of the protein (GRK2ct) has been an effective
      tool to restore compromised beta-adrenergic receptor (AR) function in heart
      failure and improve outcome. A well-characterized dysfunction in hypertension is
      attenuation of betaAR-mediated vasodilation. Therefore, we tested the role of
      inhibition of GRK2 using GRK2ct or VSM-selective GRK2 gene ablation in a renal
      artery stenosis model of elevated blood pressure (BP) [the two-kidney, one-clip
      (2K1C) model]. Use of the 2K1C model resulted in a 30% increase in conscious BP,
      a threefold increase in plasma norepinephrine levels, and a 50% increase in VSM
      GRK2 mRNA levels. BP remained increased despite VSM-specific GRK2 inhibition by
      either GRK2 knockout (GRK2KO) or peptide inhibition (GRK2ct). Although betaAR
      mediated dilation in vivo and in situ was enhanced, alpha(1)AR-mediated
      vasoconstriction was also increased. Further pharmacological experiments using
      alpha(1)AR antagonists revealed that GRK2 inhibition of expression (GRK2KO) or
      activity (GRK2ct) enhanced alpha(1D)AR vasoconstriction. This is the first study
      to suggest that VSM alpha(1D)ARs are a GRK2 substrate in vivo.

PMID- 18723765
TI  - The ubiquitin ligase Nedd4 mediates oxidized low-density lipoprotein-induced
      downregulation of insulin-like growth factor-1 receptor.
AB  - Oxidized low-density lipoprotein (LDL) is proatherogenic and induces smooth
      muscle cell apoptosis, which contributes to atherosclerotic plaque
      destabilization. We showed previously that oxidized LDL downregulates insulin
      like growth factor-1 receptor in human smooth muscle cells and that this is
      critical for induction of apoptosis. To identify mechanisms, we exposed smooth
      muscle cells to 60 mug/ml oxidized LDL or native LDL and assessed insulin-like
      growth factor-1 receptor mRNA levels, protein synthesis rate, and receptor
      protein stability. Oxidized LDL decreased insulin-like growth factor-1 receptor
      mRNA levels by 30% at 8 h compared with native LDL, and this decrease was
      maintained for up to 20 h. However, insulin-like growth factor-1 receptor protein
      synthesis rate was not altered by oxidized LDL. Pulse-chase labeling experiments
      revealed that oxidized LDL reduced insulin-like growth factor-1 receptor protein
      half-life to 12.2+/-1.7 h from 24.4+/-4.7 h with native LDL. This destabilization
      of insulin-like growth factor-1 receptor protein was accompanied by enhanced
      receptor ubiquitination. Overexpression of dominant-negative Nedd4 prevented
      oxidized LDL-induced downregulation of insulin-like growth factor-1 receptor,
      suggesting that Nedd4 was the ubiquitin ligase that mediated receptor
      downregulation. However, the proteasome inhibitors lactacystin, MG-132, and
      proteasome inhibitor-1 failed to block oxidized LDL-induced downregulation of
      insulin-like growth factor-1 receptor. Thus oxidized LDL downregulates insulin
      like growth factor-1 receptor by destabilizing the protein via Nedd4-enhanced
      ubiquitination, leading to degradation via a proteasome-independent pathway. This
      finding provides novel insights into oxidized LDL-triggered oxidant signaling and
      mechanisms of smooth muscle cell depletion that contribute to plaque
      destabilization and coronary events.

PMID- 18723766
TI  - Temporally controlled overexpression of cardiac-specific PI3Kalpha induces
      enhanced myocardial contractility--a new transgenic model.
AB  - The phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates multiple
      cellular processes including cell survival/apoptosis and growth. In the cardiac
      context, PI3Kalpha plays important roles in cardiac growth. We have shown that
      cardiac PI3K activity is highly regulated during development, with the highest
      levels found during the fetal-neonatal transition period and the lowest levels in
      the adult. There is a close relationship between cardiomyocyte proliferation and
      cardiac PI3K activity. In adult transgenic mice, however, the prolonged
      constitutive activation of PI3Kalpha in the heart results in hypertrophy. To
      develop a strategy to allow temporally controlled overexpression of cardiac
      PI3Kalpha, we engineered a tetracycline (tet) transactivator tet-off controlled
      transgenic mouse line with a conditional overexpression of a cardiac-specific
      fusion protein of the SH2 domain of p85 and p110alpha. Cardiac PI3K activity and
      Akt phosphorylation were significantly increased in adult mice after transgene
      induction following the removal of doxycycline for 2 wk. The heart weight-to-body
      weight ratio was not changed, and there were no signs of cardiomyopathy. The
      overexpression of PI3Kalpha resulted in increased left ventricular (LV) developed
      pressure and the maximal and minimal positive values of the first derivative of
      LV pressure, but not heart rate, as assessed in Langendorff hearts. Mice
      overexpressing PI3Kalpha also had increases in the levels of Ca(2+)-regulating
      proteins, including the L-type Ca(2+) channels, ryanodine receptors, and
      sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a. Thus the temporally controlled
      overexpression of cardiac PI3Kalpha does not induce hypertrophy or cardiomyopathy
      but results in increased contractility, probably via the increased expression of
      multiple Ca(2+)-regulating proteins. These distinct phenotypes suggest a
      fundamental difference between transgenic mice with temporal or prolonged
      activation of cardiac PI3Kalpha.

PMID- 18723767
TI  - Age-related changes in the biomechanics of left ventricular twist measured by
      speckle tracking echocardiography.
AB  - The increasing number and proportion of aged individuals in the population
      warrants knowledge of normal physiological changes of left ventricular (LV)
      biomechanics with advancing age. LV twist describes the instantaneous
      circumferential motion of the apex with respect to the base of the heart and has
      an important role in LV ejection and filling. This study sought to investigate
      the biomechanics behind age-related changes in LV twist by determining a broad
      spectrum of LV rotation parameters in different age groups, using speckle
      tracking echocardiography (STE). The final study population consisted of 61
      healthy volunteers (16-35 yr, n=25; 36-55 yr, n=23; 56-75 yr, n=13; 31 men). LV
      peak systolic rotation during the isovolumic contraction phase (Rot(early)), LV
      peak systolic rotation during ejection (Rot(max)), instantaneous LV peak systolic
      twist (Twist(max)), the time to Rot(early), Rot(max), and Twist(max), and
      rotational deformation delay (defined as the difference of time to basal Rot(max)
      and apical Rot(max)) were determined by STE using QLAB Advanced Quantification
      Software (version 6.0; Philips, Best, The Netherlands). With increasing age,
      apical Rot(max) (P<0.05), time to apical Rot(max) (P<0.01), and Twist(max)
      (P<0.01) increased, whereas basal Rot(early) (P<0.001), time to basal Rot(early)
      (P<0.01), and rotational deformation delay (P<0.05) decreased. Rotational
      deformation delay was significantly correlated to Twist(max) (R(2)=0.20, P<0.05).
      In conclusion, Twist(max) increased with aging, resulting from both increased
      apical Rot(max) and decreased rotational deformation delay between the apex and
      the base of the LV. This may explain the preservation of LV ejection fraction in
      the elderly.

PMID- 18723768
TI  - Role of endothelial nitric oxide synthase-derived nitric oxide in activation and
      dysfunction of cerebrovascular endothelial cells during early onsets of sepsis.
AB  - Sepsis-associated encephalopathy is an early manifestation of sepsis, resulting
      in a diffuse dysfunction of the brain. Recently, nitric oxide (NO) has been
      proposed to be one of the key molecules involved in the modulation of
      inflammatory responses in the brain. The aim of this study was to assess the role
      of NO in cerebrovascular endothelial cell activation/dysfunction during the early
      onsets of sepsis. To this end, we employed an in vitro model of sepsis in which
      cultured mouse cerebrovascular endothelial cells (MCVEC) were challenged with
      blood plasma (20% vol/vol) obtained from sham or septic (feces-induced
      peritonitis, FIP; 6 h) mice. Exposing MCVEC to FIP plasma for 1 h resulted in
      increased production of reactive oxygen species and NO as assessed by
      intracellular oxidation of oxidant-sensitive fluorochrome, dihydrorhodamine 123
      (DHR 123), and nitrosation of NO-specific probe, DAF-FM, respectively. The latter
      events were accompanied by dissociation of tight junction protein, occludin, from
      MCVEC cytoskeletal framework and a subsequent increase in FITC-dextran (3-kDa mol
      mass) flux across MCVEC grown on the permeable cell culture supports, whereas
      Evans blue-BSA (65-kDa mol mass) or FITC-dextran (10-kDa mol mass) flux were not
      affected. FIP plasma-induced oxidant stress, occludin rearrangement, and MCVEC
      permeability were effectively attenuated by antioxidant, 1
      pyrrolidinecarbodithioic acid (PDTC; 0.5 mM), or interfering with nitric oxide
      synthase (NOS) activity [0.1 mM nitro-L-arginine methyl ester (L-NAME) or
      endothelial NOS (eNOS)-deficient MCVEC]. However, treatment of MCVEC with PDTC
      failed to interfere with NO production, suggesting that septic plasma-induced
      oxidant stress in MCVEC is primarily a NO-dependent event. Taken together, these
      data indicate that during early sepsis, eNOS-derived NO exhibits proinflammatory
      characteristics and contributes to the activation and dysfunction of
      cerebrovascular endothelial cells.

PMID- 18723769
TI  - Theoretical model of blood flow autoregulation: roles of myogenic, shear
      dependent, and metabolic responses.
AB  - The autoregulation of blood flow, the maintenance of almost constant blood flow
      in the face of variations in arterial pressure, is characteristic of many tissue
      types. Here, contributions to the autoregulation of pressure-dependent, shear
      stress-dependent, and metabolic vasoactive responses are analyzed using a
      theoretical model. Seven segments, connected in series, represent classes of
      vessels: arteries, large arterioles, small arterioles, capillaries, small
      venules, large venules, and veins. The large and small arterioles respond
      actively to local changes in pressure and wall shear stress and to the downstream
      metabolic state communicated via conducted responses. All other segments are
      considered fixed resistances. The myogenic, shear-dependent, and metabolic
      responses of the arteriolar segments are represented by a theoretical model based
      on experimental data from isolated vessels. To assess autoregulation, the
      predicted flow at an arterial pressure of 130 mmHg is compared with that at 80
      mmHg. If the degree of vascular smooth muscle activation is held constant at 0.5,
      there is a fivefold increase in blood flow. When myogenic variation of tone is
      included, flow increases by a factor of 1.66 over the same pressure range,
      indicating weak autoregulation. The inclusion of both myogenic and shear
      dependent responses results in an increase in flow by a factor of 2.43. A further
      addition of the metabolic response produces strong autoregulation with flow
      increasing by a factor of 1.18 and gives results consistent with experimental
      observation. The model results indicate that the combined effects of myogenic and
      metabolic regulation overcome the vasodilatory effect of the shear response and
      lead to the autoregulation of blood flow.

PMID- 18723770
TI  - Embryonic stem cells attenuate myocardial dysfunction and inflammation after
      surgical global ischemia via paracrine actions.
AB  - Stem cell treatment may positively influence recovery and inflammation after
      shock by multiple mechanisms, including the paracrine release of protective
      growth factors. Embryonic stem cells (ESCs) are understudied and may have greater
      protective power than adult bone marrow stem cells (BMSCs). We hypothesized that
      ESC paracrine protective mechanisms in the heart (decreased injury by enhanced
      growth factor-mediated reduction of proinflammatory cytokines) would be superior
      to the paracrine protective mechanisms of the adult stem cell population in a
      model of surgically induced global ischemia. Adult Sprague-Dawley rat hearts were
      isolated and perfused via Langendorff model. Hearts were subjected to 25 min of
      warm global ischemia and 40 min of reperfusion and were randomly assigned into
      one of four groups: 1) vehicle treated; 2) BMSC or ESC preischemic treatment; 3)
      BMSC or ESC postischemic treatment; and 4) BMSC- or ESC-conditioned media
      treatment. Myocardial function was recorded, and hearts were analyzed for
      expression of tissue cytokines and growth factors (ELISA). Additionally, ESCs and
      BMSCs in culture were assessed for growth factor production (ELISA). ESC-treated
      hearts demonstrated significantly greater postischemic recovery of function (left
      ventricular developed pressure, end-diastolic pressure, and maximal positive and
      negative values of the first derivative of pressure) than BMSC-treated hearts or
      controls at end reperfusion. ESC-conditioned media (without cells) also conferred
      cardioprotection at end reperfusion. ESC-infused hearts demonstrated increased
      VEGF and IL-10 production compared with BMSC hearts. ESC hearts also exhibited
      decreased proinflammatory cytokine expression compared with MSC hearts. Moreover,
      ESCs in cell culture demonstrated greater pluripotency than MSCs. ESC paracrine
      protective mechanisms in surgical ischemia are superior to those of adult stem
      cells.

PMID- 18723771
TI  - Ether-linked diglycerides inhibit vascular smooth muscle cell growth via
      decreased MAPK and PI3K/Akt signaling.
AB  - Diglycerides (DGs) are phospholipid-derived second messengers that regulate PKC
      dependent signaling pathways. Distinct species of DGs are generated from
      inflammatory cytokines and growth factors. Growth factors increase diacyl- but
      not ether-linked DG species, whereas inflammatory cytokines predominately
      generate alkyl, acyl- and alkenyl, acyl-linked DG species in rat mesenchymal
      cells. These DG species have been shown to differentially regulate protein kinase
      C (PKC) isotypes. Ester-linked diacylglycerols activate PKC-epsilon and cellular
      proliferation in contrast to ether-linked DGs, which lead to growth arrest
      through the inactivation of PKC-epsilon. It is now hypothesized that ether-linked
      DGs inhibit mitogenesis through the inactivation of ERK and/or Akt signaling
      cascades. We demonstrate that cell-permeable ether-linked DGs reduce vascular
      smooth muscle cell growth by inhibiting platelet-derived growth factor-stimulated
      ERK in a PKC-epsilon-dependent manner. This inhibition is specific to the ERK
      pathway, since ether-linked DGs do not affect growth factor-induced activation of
      other family members of the MAPKs, including p38 MAPK and c-Jun NH(2)-terminal
      kinases. We also demonstrate that ether-linked DGs reduce prosurvival
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling, independent of PKC-epsilon,
      by diminishing an interaction between the subunits of PI3K and not by affecting
      protein phosphatase 2A or lipid (phosphatase and tensin homologue deleted in
      chromosome 10) phosphatases. Taken together, our studies identify ether-linked
      DGs as potential adjuvant therapies to limit vascular smooth muscle migration and
      mitogenesis in atherosclerotic and restenotic models.

PMID- 18723773
TI  - Gambling as a search for justice: examining the role of personal relative
      deprivation in gambling urges and gambling behavior.
AB  - The present article explores the hypothesis that gambling might serve a justice
      seeking function for some people, as gambling might offer a means to pursuing
      desirable outcomes that people feel they deserve but might be unable or unwilling
      to attain through conventional means. In Study 1, across two separate samples,
      self-reports of personal relative deprivation predict problem gambling and
      gambling urges over and above relevant control variables. In Study 2, the authors
      manipulate personal relative deprivation by informing participants that they have
      either less or more discretionary income than "similar others." They then give
      participants $20 and the opportunity to gamble. The results show that a greater
      percentage of participants who are "relatively deprived" (vs. "not relatively
      deprived") opt to gamble. Two manipulation validation studies demonstrate that
      the "relatively deprived" participants are preoccupied with justice during a
      modified Stroop task and feel resentful. Implications for understanding why
      people gamble are discussed.

PMID- 18723774
TI  - Determining the role of Tie-dyed1 in starch metabolism: epistasis analysis with a
      maize ADP-glucose pyrophosphorylase mutant lacking leaf starch.
AB  - In regions of their leaves, tdy1-R mutants hyperaccumulate starch. We propose 2
      alternative hypotheses to account for the data, that Tdy1 functions in starch
      catabolism or that Tdy1 promotes sucrose export from leaves. To determine whether
      Tdy1 might function in starch breakdown, we exposed plants to extended darkness.
      We found that the tdy1-R mutant leaves retain large amounts of starch on
      prolonged dark treatment, consistent with a defect in starch catabolism. To
      further test this hypothesis, we identified a mutant allele of the leaf expressed
      small subunit of ADP-glucose pyrophosphorylase (agps-m1), an enzyme required for
      starch synthesis. We determined that the agps-m1 mutant allele is a molecular
      null and that plants homozygous for the mutation lack transitory leaf starch.
      Epistasis analysis of tdy1-R; agps-m1 double mutants demonstrates that Tdy1
      function is independent of starch metabolism. These data suggest that Tdy1 may
      function in sucrose export from leaves.

PMID- 18723772
TI  - Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after
      acidosis in rat heart. Role of Ca2+/calmodulin-dependent protein kinase II.
AB  - Returning to normal pH after acidosis, similar to reperfusion after ischemia, is
      prone to arrhythmias. The type and mechanisms of these arrhythmias have never
      been explored and were the aim of the present work. Langendorff-perfused rat/mice
      hearts and rat-isolated myocytes were subjected to respiratory acidosis and then
      returned to normal pH. Monophasic action potentials and left ventricular
      developed pressure were recorded. The removal of acidosis provoked ectopic beats
      that were blunted by 1 muM of the CaMKII inhibitor KN-93, 1 muM thapsigargin, to
      inhibit sarcoplasmic reticulum (SR) Ca(2+) uptake, and 30 nM ryanodine or 45 muM
      dantrolene, to inhibit SR Ca(2+) release and were not observed in a transgenic
      mouse model with inhibition of CaMKII targeted to the SR. Acidosis increased the
      phosphorylation of Thr(17) site of phospholamban (PT-PLN) and SR Ca(2+) load.
      Both effects were precluded by KN-93. The return to normal pH was associated with
      an increase in SR Ca(2+) leak, when compared with that of control or with
      acidosis at the same SR Ca(2+) content. Ca(2+) leak occurred without changes in
      the phosphorylation of ryanodine receptors type 2 (RyR2) and was blunted by KN
      93. Experiments in planar lipid bilayers confirmed the reversible inhibitory
      effect of acidosis on RyR2. Ectopic activity was triggered by membrane
      depolarizations (delayed afterdepolarizations), primarily occurring in epicardium
      and were prevented by KN-93. The results reveal that arrhythmias after acidosis
      are dependent on CaMKII activation and are associated with an increase in SR
      Ca(2+) load, which appears to be mainly due to the increase in PT-PLN.

PMID- 18723775
TI  - sigma-1 receptor modulation of acid-sensing ion channel a (ASIC1a) and ASIC1a
      induced Ca2+ influx in rat cortical neurons.
AB  - Acid-sensing ion channels (ASICs) are proton-gated cation channels found in
      peripheral and central nervous system neurons. The ASIC1a subtype, which has high
      Ca2+ permeability, is activated by ischemia-induced acidosis and contributes to
      the neuronal loss that accompanies ischemic stroke. Our laboratory has shown that
      activation of sigma receptors depresses ion channel activity and [Ca2+](i)
      dysregulation during ischemia, which enhances neuronal survival. Whole-cell patch
      clamp electrophysiology and fluorometric Ca2+ imaging were used to determine
      whether sigma receptors regulate the function of ASIC in cultured rat cortical
      neurons. Bath application of the selective ASIC1a blocker, psalmotoxin1,
      decreased proton-evoked [Ca2+](i) transients and peak membrane currents,
      suggesting the presence of homomeric ASIC1a channels. The pan-selective sigma
      1/sigma-2 receptor agonists, 1,3-di-o-tolyl-guanidine (100 microM) and opipramol
      (10 microM), reversibly decreased acid-induced elevations in [Ca2+](i) and
      membrane currents. Pharmacological experiments using sigma receptor-subtype
      specific agonists demonstrated that sigma-1, but not sigma-2, receptors inhibit
      ASIC1a-induced Ca2+ elevations. These results were confirmed using the
      irreversible sigma receptor antagonist metaphit (50 microM) and the selective
      sigma-1 antagonist BD1063 (10 nM), which obtunded the inhibitory effects of the
      sigma-1 agonist, carbetapentane. Activation of ASIC1a was shown to stimulate
      downstream Ca2+ influx pathways, specifically N-methyl-D-aspartate and (+/-)
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate receptors and
      voltage-gated Ca2+ channels. These subsequent Ca2+ influxes were also inhibited
      upon activation of sigma-1 receptors. These findings demonstrate that sigma-1
      receptor stimulation inhibits ASIC1a-mediated membrane currents and consequent
      intracellular Ca2+ accumulation. The ability to control ionic imbalances and Ca2+
      dysregulation evoked by ASIC1a activation makes sigma receptors an attractive
      target for ischemic stroke therapy.

PMID- 18723776
TI  - Antiatherosclerotic effects of a novel synthetic tissue-selective steroidal liver
      X receptor agonist in low-density lipoprotein receptor-deficient mice.
AB  - Liver X receptor (LXR) agonists have the potential to treat atherosclerosis based
      on their ability to enhance reverse cholesterol transport. However, their side
      effects, such as induction of liver lipogenesis and triglyceridemia, may limit
      their pharmaceutical development. In contrast to the nonsteroidal LXR agonist N
      (2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1
      (trifluoromethyl)ethyl]phenyl]-benzenesulfonamide (T0901317), 3alpha, 6alpha, 24
      trihydroxy-24, 24-di(trifluoromethyl)-5beta-cholane (ATI-829), a novel potent
      synthetic steroidal LXR agonist, was a poor inducer of sterol regulatory element
      binding protein 1c expression in hepatoma HepG2 cells, whereas both compounds
      increased ABCA1 expression in macrophage THP-1 cells. In male low-density
      lipoprotein receptor-deficient mice, ATI-829 selectively activated LXR target
      gene expression in mouse intestines and macrophages but not in the liver. A
      significant increase in liver triglyceride and plasma triglyceriderich small very
      low-density lipoprotein (VLDL) was observed in T0901317 but not ATI-829-treated
      mice. Compared with vehicle-treated mice, atherosclerosis development was
      significantly inhibited in the innominate artery after treatment with either
      compound. However, in the aortic root, inhibition of atherosclerosis was only
      observed in the right (right coronary artery-associated sinus) but not the left
      coronary-related sinus (left coronary artery-associated sinus; LC) of mice
      treated with either compound. Lesions in the innominate artery were less complex
      after treatment with either compound and contained mostly macrophage foam cells.
      In contrast, LC lesions were more complex and had a large collagen-positive
      fibrous cap and less macrophage foam cell area after treatment with either
      compound. The T0901317-induced hypertriglyceridemia was accompanied by an
      increase in small triglyceride-rich VLDL that may influence LXR agonist-mediated
      antiatherosclerotic effects at certain vascular sites. ATI-829, by selectively
      activating LXR in certain tissues without inducing hypertriglyceridemia, is a
      good candidate for drug development.

PMID- 18723777
TI  - A novel human multidrug resistance gene MDR1 variant G571A (G191R) modulates
      cancer drug resistance and efflux transport.
AB  - The human multidrug resistance gene MDR1 encodes a membrane-bound transporter P
      glycoprotein (Pgp) that confers the drug resistance of cancer cells by mediating
      an ATP-dependent drug efflux transport. We and others have reported a number of
      functionally significant MDR1 variants, including G1199A and G1199T, that
      modulate cancer drug resistance and intracellular levels of antivirals. In this
      report, we describe a novel G571A variant of MDR1 detected in 6.4% of leukemia
      patients. Because this nucleotide modification gives rise to an amino acid change
      from Gly to Arg at the 191 amino acid position of Pgp, we have developed and
      characterized the functional affect of the G571A variant in stable, recombinant
      cells. Using six chemotherapeutic drugs, doxorubicin HCl, daunorubicin HCl,
      vinblastine sulfate, vincristine sulfate, taxanes (paclitaxel), and
      epipodophyllotoxin (etoposide, VP-16), we found that the MDR1(571A) variant
      selectively reduced the degree of Pgp-mediated resistance in drug-dependent
      manner. Although there was a minimal effect on doxorubicin and daunorubicin, the
      MDR1-dependent resistance on vinblastine, vincristine, paclitaxel, and etoposide
      was reduced by approximately 5-fold. The increased drug sensitivity in
      MDR1(571A), compared with MDR1(wt), paralleled the intracellular drug levels.
      These data suggest that individuals with this novel MDR1 variant, the 571A
      genotype, may be more sensitive to the specific anticancer drugs that are Pgp
      substrates.

PMID- 18723778
TI  - Providing stability in oxygenation for preterm infants: is transcutaneous oxygen
      monitoring really better than pulse oximetry?

PMID- 18723779
TI  - Neonatal intrahepatocellular lipid.
AB  - There is increasing evidence that preterm birth is a risk factor for the
      development of adiposity associated disease, although the pathophysiological
      basis is unclear. We have previously shown that preterm infants have increased
      internal abdominal (visceral) adiposity by term. In adults increased internal
      adiposity is associated with elevated intrahepatocellular lipid (IHCL). We
      measured IHCL using (1)H NMR spectroscopy in 26 infants (eight healthy preterm-at
      term and 18 term-born) and compared values with a reference group of 32 adults.
      There was no significant difference between adult and term-born IHCL content. In
      preterm-at-term infants IHCL was significantly elevated when compared with term
      born infants and with adults (IHCL CH2/water median (interquartile range):
      preterm 1.69 (1.04-3.53), term 0.21 (0-0.54) and adult 0.55 (0.08-1.57).

PMID- 18723780
TI  - Medicine or surgery for patent ductus arteriosus?

PMID- 18723781
TI  - The new nasogastric tubes: implications for neonatal practice.

PMID- 18723782
TI  - Trends in infant mortality from necrotising enterocolitis in England and Wales
      and the USA.

PMID- 18723783
TI  - Effects of time on pH and gas values in the blood contained in the umbilical cord
      of a subgroup of newborns with acidosis.

PMID- 18723784
TI  - Noise levels during neonatal helmet CPAP.

PMID- 18723785
TI  - Tissue plasminogen activator therapy for renal venous thrombosis.

PMID- 18723786
TI  - Linezolid for treatment of catheter-related cerebrospinal fluid infections in
      preterm infants.

PMID- 18723787
TI  - Postnatal glucocorticoids in preterm neonates: use in French neonatal centres in
      2006.

PMID- 18723790
TI  - Letter to the editor: one health initiative.

PMID- 18723791
TI  - Veterinary medicine is public health.
AB  - The symposium Partnerships for Preparedness: Future Directions of Schools of
      Public Health and Colleges of Veterinary Medicine documents the importance of
      further integration between the fields of veterinary medicine and public health
      to protect our nation from public-health emergencies. Current areas targeted for
      improved collaboration include academic programs, public policy, workforce
      training, and research.

PMID- 18723792
TI  - Collaboration in public health: a new global imperative.

PMID- 18723793
TI  - The importance of diversity to public health.

PMID- 18723794
TI  - Prevention and preparedness: working together to improve public health.

PMID- 18723795
TI  - Joint degree programs in public health.
AB  - Public health and veterinary medicine share a focus on population health and
      primary prevention, along with a commitment to preparedness, response, and
      recovery in the event of disease outbreaks. Public-health and veterinary
      professional degree programs share commonalities in their educational
      accreditation requirements related to epidemiology and public-health practice.
      The initiation of a number of joint professional degree programs over the last
      five years, including the joint Doctor of Veterinary Medicine and Master of
      Public Health (DVM/MPH), represents an exciting development for inter
      professional education for veterinarians interested in public health. Various
      models for joint DVM/MPH educational programs are discussed, including pre
      veterinary public-health credentialing, integrated programs, and post-DVM
      executive programs. Collaborations between colleges of veterinary medicine and
      schools of public health show great promise in both educational and research
      innovation.

PMID- 18723796
TI  - A new approach to teaching veterinary public health at the Ohio State University.
AB  - Public-health practitioners with expertise in the area of veterinary public
      health are expected to understand the prevention and control of zoonotic
      infectious diseases in both human and animal populations. This focus on multiple
      species is what makes the veterinary public health (VPH) official unique. The
      development of a new VPH specialization within the existing Master of Public
      Health (MPH) degree program at the Ohio State University represents a significant
      new collaboration between the College of Veterinary Medicine and the College of
      Public Health. The main objective of the VPH specialization is to educate and
      train professionals to provide them with the skills, knowledge, and resources
      necessary to protect and improve human health using a One Medicine approach. The
      program targets a population of students who will likely enter the professional
      veterinary medicine curriculum but have one year available to enhance their
      preparatory training in health sciences before beginning the program. A core
      series of VPH courses was initiated to complement the existing MPH course
      requirements. The program has been successful in attracting students from the
      primary target population, but it has also attracted students wanting the MPH as
      a terminal degree and veterinarians returning to school to expand their career
      options.

PMID- 18723797
TI  - A flexible approach to training veterinarians in public health: an overview and
      early assessment of the DVM/MPH dual-degree program at the University of
      Minnesota.
AB  - As a result of the growing need for public-health veterinarians, novel
      educational programs are essential to train future public-health professionals.
      The University of Minnesota School of Public Health, in collaboration with the
      College of Veterinary Medicine, initiated a dual DVM/MPH program in 2002. This
      program provides flexibility by combining distance learning and on-campus courses
      offered through a summer public-health institute. MPH requirements are completed
      through core courses, elective courses in a focus area, and an MPH project and
      field experience. Currently, more than 100 students representing 13 veterinary
      schools are enrolled in the program. The majority of initial program graduates
      have pursued public-practice careers upon completion of the program. Strengths of
      the Minnesota program design include accessibility and an environment to support
      multidisciplinary training. Continued assessment of program graduates will allow
      for evaluation and adjustment of the program in the coming years.

PMID- 18723798
TI  - The cooperative University of Iowa / Iowa State University MPH program.
AB  - Public health is an important component of veterinary medicine. In the last 10
      years, there has been growing recognition of the need to increase the number of
      veterinarians trained in public health. The Center for Food Security and Public
      Health (CFSPH) at Iowa State University (ISU), College of Veterinary Medicine,
      received a grant from the Centers for Disease Control and Prevention (CDC) to
      support veterinarians working at CFSPH while pursuing the Master of Public Health
      degree. CFSPH and ISU administrators worked with the University of Iowa (UI)
      College of Public Health to establish three cooperative programs for
      veterinarians to earn the MPH degree. This article describes how these programs
      were developed and how they operate. (1) Between 2002 and 2005, CFSPH used funds
      provided by the CDC to support 15 veterinarians as they worked for CFSPH and
      toward the MPH degree. As the program grew, distance-education methods such as
      the Internet, Polycom videoconferencing, and the Iowa Communications Network
      (ICN) were incorporated. (2) A concurrent DVM/MPH degree is now offered; students
      can complete both degrees in four years. As of January 2008, three students have
      received their DVM and MPH degrees and 16 students are enrolled in the program.
      (3) In June 2007, the UI and ISU launched a distance MPH program for
      veterinarians working in private practice, industry, and government. Eight
      veterinarians are participating in the program, which includes two two-week, in
      person summer sessions, with the remainder of the coursework taken at a distance
      via the Internet.

PMID- 18723799
TI  - The dual DVM/MPH degree at the University of Wisconsin--Madison: a uniquely
      interdisciplinary collaboration.
AB  - The University of Wisconsin-Madison (UWM) launched a new Master of Public Health
      (MPH) degree program in 2005. This 42-credit MPH degree consists of 18 core and
      14 elective course credits, two seminar credits, and eight field
      project/culminating experience credits. Unique strengths of the program include
      its strongly interdisciplinary philosophy, encompassing both health science
      (human medicine, veterinary medicine, pharmacy, nursing) and social science units
      on campus, and its emphasis on service learning through instructional and field
      project ties to the public-health community of the state and beyond. To date, the
      program has admitted 87 students, including full-time students as well as part
      time students who continue to work in the health care and/or public-health
      sectors. The program is currently proceeding with the process for accreditation
      through the Council for Education in Public Health. In 2007, a formal dual
      DVM/MPH program was approved to allow students to integrate DVM and MPH training
      and complete both degrees in a total of five years. Nine MPH students over the
      first three years of admissions have been individuals affiliated with veterinary
      medicine (five DVM students and four post-graduate veterinarians).

PMID- 18723800
TI  - The combined master of public health program at Tufts University.
AB  - The Combined Master of Public Health program at Tufts University unites medical
      and veterinary medical students in a four-year curriculum that integrates
      students' clinical studies with simultaneous studies on population health. Thirty
      years ago, Tufts University adopted a "One Medicine" approach to teaching health
      professionals. That perspective has been updated as "One Health" and is now being
      applied in a university environment that emphasizes interdisciplinary education,
      a global outlook, and civic engagement.

PMID- 18723801
TI  - Public-health education at Kansas State University.
AB  - What are veterinary medical and public-health professionals doing to remedy the
      immediate and impending shortages of veterinarians in population health and
      public practice? This question was addressed at the joint symposium of the
      Association of American Veterinary Medical Colleges and the Association of
      Schools of Public Health, held in April 2007. Thinking locally, faculty and
      students at Kansas State University (KSU) asked similar questions after attending
      the symposium: What are we doing within the College of Veterinary Medicine to
      tackle this problem? What can we do better with new collaborators? Both the
      professional veterinary curriculum and the Master of Public Health (MPH) at KSU
      provide exceptional opportunities to address these questions. Students are
      exposed to public health as a possible career choice early in veterinary school,
      and this exposure is repeated several times in different venues throughout their
      professional education. Students also have opportunities to pursue interests in
      population medicine and public health through certificate programs, summer
      research programs, study abroad, and collaborations with contributing
      organizations unique to KSU, such as its Food Science Institute, National
      Agricultural Biosecurity Center, and Biosecurity Research Institute. Moreover,
      students may take advantage of the interdisciplinary nature of public-health
      education at KSU, where collaborations with several different colleges and
      departments within the university have been established. We are pleased to be
      able to offer these opportunities to our students and hope that our experience
      may be instructive for the development of similar programs at other institutions,
      to the eventual benefit of the profession at large.

PMID- 18723802
TI  - One medicine, one university: the DVM/MPH program at the University of Illinois.
AB  - The University of Illinois at Urbana-Champaign College of Veterinary Medicine
      (UIUC-CVM) and the University of Illinois-Chicago School of Public Health (UIC
      SPH) are in the fourth year of a collaborative Doctor of Veterinary Medicine and
      Master of Public Health dual-degree program. The two campuses, one urban and one
      rural, are 150 miles apart but are sister schools within the University of
      Illinois system. This article describes the origin of the program, how the
      program functions across two campuses, its academic focus, required coursework,
      and research projects designed to fulfill the program's capstone requirements.
      The article shows how two campuses can be linked through a combination of online
      and on-site didactic coursework, briefly describes innovative proposals for
      projects within the United States and abroad, and highlights faculty committed to
      educating cross-trained public-health professionals while addressing the national
      need for veterinarians trained in public health. The authors also discuss how the
      dual-degree program has led to the formation of the Illinois Center for One
      Medicine, One Health (ICOMOH), an intra-university collaboration focusing on the
      interface of human, animal, and ecosystem health.

PMID- 18723803
TI  - Public health education at Michigan State University.
AB  - Many reports have highlighted the need for the veterinary profession to fill
      critical shortages of veterinarians in public health and food safety. Michigan
      State University's College of Veterinary Medicine offers educational programs
      within the professional veterinary curriculum, as well as graduate degree
      programs, to meet these societal needs. Within the scope of the professional
      veterinary curriculum, educational opportunities in public health include
      clerkships in veterinary public health and an innovative Web-based curriculum on
      judicious use of antimicrobials. For graduate degree programs, Michigan State
      University has a memorandum of understanding with the University of Minnesota for
      the Master of Public Health degree and an innovative Online Professional Master
      of Science in Food Safety degree program. A new option available is the
      opportunity for veterinary students to pursue the Master of Science in Food
      Safety concurrently with the DVM (DVM/MS in Food Safety). These educational
      programs will prepare graduates to meet societal needs in public health and food
      safety.

PMID- 18723804
TI  - Linking veterinary and human public-health education: collaborations at the
      University Of Tennessee.
AB  - The increasing demand for veterinarians in public health has created an
      environment for innovative educational approaches, providing opportunities for
      veterinary students to gain additional education in public health. At the
      University of Tennessee, this environment has enabled a collaboration between the
      College of Veterinary Medicine and the College of Education, Health, and Human
      Sciences to establish a veterinary concentration in an existing Master of Public
      Health degree program. The veterinary public-health concentration was approved in
      2004. In addition, other courses and initiatives have been developed at the
      College of Veterinary Medicine, creating stronger collaborations with academic
      units and public-health professionals.

PMID- 18723805
TI  - Enhancing food-safety education through shared teaching resources.
AB  - The American public is concerned about food safety, and there is a growing
      realization that we are ill equipped to handle major food-borne illness outbreaks
      and bioterrorism. Since veterinary medicine plays an important role in assuring
      the safety of our nation's food supply, we would like to present to veterinary
      and public health educators a newly emerging resource for food-safety educational
      materials. This article describes an integrative collaborative approach for the
      creation and dissemination of engaging food-safety teaching resources for
      veterinary faculty. This USDA-funded project, Design to Dissemination: Developing
      Materials and Repository for Integrative Veterinary Food Safety Education,
      involves expert teachers in diverse fields and from many veterinary schools. The
      purpose of the project is to create materials that teach students food safety
      from farm to fork, and it offers teachers clinically relevant teaching resources
      that are difficult to create or locate. The educational materials are being
      created as smaller "building blocks" of content, commonly referred to as
      "learning objects" (LOs), focused on individual learning objectives. These
      learning objects are placed in the Veterinary Food Safety Education Learning
      Object Repository, where they are catalogued, stored, and kept accessible and
      where faculty can search, evaluate, and download teaching materials to use in
      their courses. In this way the learning objects can be more easily shared and
      reused or repurposed for other courses and applications. With this article we
      hope to excite faculty in veterinary schools and public-health programs and
      encourage them to use the repository and participate in piloting the educational
      materials.

PMID- 18723806
TI  - Veterinary public health in a problem-based learning curriculum at the Western
      University of Health Sciences.
AB  - As detailed in the Association of Schools of Public Health / Association of
      American Veterinary Medical Colleges 2007 Joint Symposium on Veterinary Public
      Health, veterinary public health (VPH) can no longer be viewed as a unique sub
      specialty of veterinary medicine. Rather, its practice pervades nearly every
      aspect of the veterinary profession, regardless of whether the practitioner is
      engaged in small-animal, large-animal, research, corporate, or military practice.
      In congruence with the practice of VPH, the teaching of VPH should also pervade
      nearly every aspect of veterinary education. Accordingly, at Western University
      of Health Sciences, College of Veterinary Medicine (WU-CVM), public health is not
      simply taught as an individual course but, rather, is interwoven into almost
      every aspect of the curriculum, continually emphasizing the relevance of this
      discipline to the practice of veterinary medicine. This article outlines the
      teaching philosophy of WU-CVM, provides an overview of the curriculum, and
      describes the integral nature of public health throughout all four years of the
      educational program.

PMID- 18723807
TI  - Public health education at the University of California, Davis: past, present,
      and future programs.
AB  - This article reviews the history of public-health education at the University of
      California, Davis, from the inception of the Master of Preventive Veterinary
      Medicine Program in the School of Veterinary Medicine through the creation of the
      Master of Public Health Program offered jointly by the Schools of Medicine and
      Veterinary Medicine. The long history of collaborative teaching and research
      between the schools, as well as the university's close proximity to and
      relationship with numerous university-affiliated and state public-health
      agencies, has created remarkable opportunities for novel and creative public
      health education. The university is already anticipating the approval of a School
      of Public Health on its campus, which will create even more educational
      opportunities in both human and veterinary public-health disciplines. Given the
      projected shortfall of veterinarians entering such fields, the opportunity of a
      novel Doctor of Public Health degree program specifically suited to the needs of
      veterinary medicine is also discussed as a means of addressing this shortage.

PMID- 18723808
TI  - Veterinarians and public practice at the Virginia-Maryland Regional College of
      Veterinary Medicine: building on a tradition of expertise and partnership.
AB  - The Virginia-Maryland Regional College of Veterinary Medicine (VMRCVM), a
      regional veterinary college for Maryland and Virginia, has a long and unique
      tradition of encouraging careers in public and corporate veterinary medicine. The
      VMRCVM is home to the Center for Public and Corporate Veterinary Medicine
      (CPCVM), and each year approximately 10% of the veterinary students choose the
      public/corporate veterinary medicine track. The faculty of the CPCVM, and their
      many partners from the veterinary public practice community, teach in the
      veterinary curriculum and provide opportunities for students locally, nationally,
      and internationally during summers and the final clinical year. Graduates of the
      program work for government organizations, including the US Department of
      Agriculture, the Food and Drug Administration, and the Centers for Disease
      Control and Prevention, as well as in research, in industry, and for non
      governmental organizations. Recent activities include securing opportunities for
      students, providing career counseling for graduate veterinarians interested in
      making a career transition, delivering continuing education, and offering a
      preparatory course for veterinarians sitting the board examination for the
      American College of Veterinary Preventive Medicine. As the VMRCVM moves forward
      in recognition of the changing needs of the veterinary profession, it draws on
      its tradition of partnership and capitalizes on the excellence of its existing
      program. Future plans for the CPCVM include possible expansion in the fields of
      public health, public policy, international veterinary medicine, organizational
      leadership, and the One Health initiative. Quality assurance and evaluation of
      the program is ongoing, with recognition that novel evaluation approaches will be
      useful and informative.

PMID- 18723809
TI  - Public-health instruction necessary to supplement the veterinary professional
      curriculum: the DVM/MPH coordinated-degree program at Auburn University.
AB  - To meet long-term needs, many veterinary colleges and schools are participating
      in dual-degree DVM/MPH programs. Auburn University's College of Veterinary
      Medicine and the School of Public Health at the University of Alabama at
      Birmingham have developed a coordinated-degree curriculum in which the DVM and
      the MPH are not necessarily awarded simultaneously. Other opportunities at Auburn
      include Public Health Careers Day, trips to the Centers for Disease Control and
      Prevention, several elective courses related to veterinary epidemiology, and
      online access to the Emerging and Exotic Diseases of Animals course available
      from the Veterinary Information Network. We have been able to increase our
      students' exposure to the role of the veterinarian in public health and to
      develop a program to augment their training in public practice.

PMID- 18723810
TI  - Purdue University graduate certificate program in Veterinary Homeland Security.
AB  - Our nation lacks a critical mass of professionals trained to prevent and respond
      to food- and animal-related emergencies. Training veterinarians provides an
      immediate means of addressing this shortage of experts. Achievement of critical
      mass to effectively address animal-related emergencies is expedited by concurrent
      training of professionals and graduate students in related areas. Purdue
      University offers a Web-based Graduate Certificate in Veterinary Homeland
      Security to address this special area of need. The program is a collaborative
      effort among the Purdue University School of Veterinary Medicine, the Purdue
      Homeland Security Institute, the Indiana State Board of Animal Health, the
      Indiana State Police, and others with the overall goal of increasing capacity and
      preparedness to manage animal-related emergencies. Individuals with expertise in
      veterinary medicine, public health, animal science, or homeland security are
      encouraged to participate. The Web-based system allows courses to be delivered
      efficiently and effectively around the world and allows participants to continue
      their graduate education while maintaining full-time jobs. Participants enhance
      their understanding of natural and intentional threats to animal health,
      strengthen their skills in managing animal-health emergencies, and develop
      problem-solving expertise to become effective members of animal emergency
      response teams and of their communities. Students receive graduate credit from
      Purdue University that can be used toward the certificate and toward an advanced
      graduate degree. Currently, 70 participants from 28 states; Washington, DC;
      Singapore; and Bermuda are enrolled.

PMID- 18723811
TI  - Reviewing the undergraduate veterinary curriculum in Finland for control tasks in
      veterinary public health.
AB  - To review and develop the undergraduate veterinary curriculum on official control
      in veterinary public health, an electronic survey was sent to 204 Finnish
      veterinarians employed in the field of food hygiene in 2005. The response rate
      was 44%. Most frequently cited as strengths of the current curriculum were
      extensive education and good knowledge. Respondents considered the main
      challenges in their work to be a wide field of activity, organizational changes,
      financial resources, organization of substitutes, and collaboration with decision
      makers. Of the 23 items to be included in the undergraduate curriculum,
      therefore, respondents prioritized state and local decision making, the role of
      the public servant, and leadership and management in the area of social factors;
      in the field of practical control work, in-house control systems, organizations
      and responsibilities, control techniques, and planning and targeting of controls
      were prioritized. Of areas traditionally covered in the undergraduate curriculum,
      legislation; legal proceedings and implications of controls; risks to human,
      animal, and plant health; and hazards in feed, animal, and food production were
      stated to be the most important. Although respondents were generally content with
      their career choice, veterinary public health tasks were not their first choice
      of career path immediately after graduation. Based on these findings, more
      attention should be focused on social aspects and practical training in official
      control in the undergraduate veterinary curriculum. The survey results also
      highlight the contrasts between society's needs and veterinarians' motivations
      and career-path expectations, which pose a significant challenge for future
      curricula.

PMID- 18723812
TI  - Training veterinary personnel for effective identification and diagnosis of
      exotic animal diseases.
AB  - The requirements for exotic animal disease (EAD) training were considered at a
      workshop organized for those with responsibilities for EAD response management in
      the different states of Australia, with the objective of identifying the optimum
      strategy for training veterinarians to identify and act upon EADs. It was
      concluded that there should be specialized within-country training in EAD
      recognition for an elite group of diagnostic veterinarians who are required to
      recognize the major exotic diseases of animals, instigate the correct procedures
      to confirm the diagnosis of the disease, and undertake appropriate measures for
      effective initial management of the disease. The use of live, deliberately
      infected animals for demonstration purposes is not currently supported by any
      research indicating an improved learning outcome compared with that from
      alternatives, such as videos, necropsy specimens, and dedicated computer-aided
      learning packages. Therefore, ethical requirements to minimize the use of animals
      in teaching and research may prevent live-animal use. It is concluded that
      training should take place within each country via a course of instruction that
      includes an initial intensive course followed by continued professional
      development, with examination of knowledge at the end of each.

PMID- 18723813
TI  - Assessing bioterrorism preparedness and response of rural veterinarians:
      experiences and training needs.
AB  - Veterinarians play a unique role in emergency preparedness and response, and
      federal agencies and academic institutions therefore allocate considerable
      resources to provide training to enhance their readiness. However, the level of
      preparedness of veterinarians in many rural regions is yet to be improved. This
      article reports an assessment of the bioterrorism preparedness, specifically the
      experience and training needs, of rural veterinarians in North Texas. The study
      employed a cross-sectional design with a study population that included all
      veterinarians (N = 352) in the 37 counties within Texas Department of State
      Health Services Regions 2 and 3. Data on veterinarians practicing or residing in
      the target region were obtained from the Texas State Board of Veterinary Medical
      Examiners. The response rate was 35% (n = 121). Results indicate that chemical
      exposure was the condition most frequently seen and treated, followed by botulism
      and anthrax. The majority (80%) of respondents indicated that they had not
      previously participated in training related to bioterrorism preparedness, and
      many (41%) also indicated a willingness to participate in a state health
      department-initiated bioterrorism response plan. However, only 18% were confident
      in their ability to diagnose and treat bioterrorism cases. These results suggest
      that many North Texas veterinarians practicing in rural regions could benefit
      from additional training in bioterrorism preparedness and response. An area in
      particular need of further training is the diagnosis and treatment of Category A
      agents. Federal, state, and local health agencies are urged to increase training
      opportunities and to make additional efforts to involve veterinarians in
      bioterrorism preparedness and response.

PMID- 18723814
TI  - The need for public-health veterinarians as seen by future employers.
AB  - Future employers of veterinarians working in public health see a fast-growing
      demand. Emerging zoonotic diseases, bio-security threats, and food-safety
      problems all require the expertise of veterinarians with a focus on complex,
      global problems that span both human and animal health. The Public Health Task
      Force of the Association of American Veterinary Medical Colleges convened a group
      of stakeholders representing various branches of the US federal government, state
      and local governments, and professional societies to discuss their needs for
      public-health veterinarians. This article discusses those needs, the broader
      societal needs that require veterinarians with public-health expertise, and the
      implications of these for educational programs to train DVMs in public-health
      issues.

PMID- 18723815
TI  - Teaching nutrition to the left and right brain: an overview of learning styles.
AB  - Functioning effectively as a veterinarian requires proficiency in multiple
      learning styles. Whether the goal is to design a nutrition course, plan a
      veterinary curriculum, or help students develop interpersonal, communication, and
      leadership skills, students benefit when content, design, and delivery are
      balanced to meet their learning-style preferences. An overview of four different
      learning style models is presented: the Myers-Briggs Type Indicator (MBTI),
      Kolb's Learning Style Model, the Felder-Silverman Learning Style Model, and the
      Herrmann Brain Dominance Instrument (HBDI). A whole-brain approach (HBDI) was
      used in the development and implementation of the small-animal clinical nutrition
      course at the University of Minnesota College of Veterinary Medicine. One
      educational objective of this course is to help students develop mental
      dexterity, increasing their proficiency in both their preferred and their less
      preferred modes of learning. The instructional goals are to deliver the content
      of the small-animal clinical nutrition course through exercises that meet the
      needs of learners in each thinking quadrant (left and right, cerebral and limbic)
      at least part of the time. Examples of exercises are presented to portray a
      balanced or whole-brain approach to teaching clinical nutrition.

PMID- 18723816
TI  - Teaching and assessing nutrition competence in a changing curricular environment.
AB  - In the past, the required introductory veterinary nutrition course at Michigan
      State University's College of Veterinary Medicine (MSU-CVM) has provided 29 hours
      of didactic lectures, with student performance evaluated by short-answer or
      multiple-choice questions. Because of a 50% reduction in allotted course credits
      and a change in prerequisites for admission, the course is being redesigned to
      focus on three of 29 nutrition competencies outlined by the American College of
      Veterinary Nutrition. Professional communication skills will be developed through
      small-group learning experiences, case-based problems, and videotaped interviews
      with standardized clients to teach and assess nutrition competencies. Assessment
      strategies will differ from traditional multiple-choice examinations and include
      pre- and post-course self-efficacy ratings, written evaluations from trained
      standardized clients, and oral and written evaluations from coaches or
      facilitators.

PMID- 18723817
TI  - Teaching nutrition to student veterinary technicians.
AB  - Graduates of veterinary technology programs must have the knowledge and skills to
      understand, implement, and encourage owner compliance with appropriate feeding
      recommendations for healthy animals and therapeutic regimens to promote optimal
      health, enhance recovery, and manage chronic disease conditions. This article
      describes nutrition education for veterinary technology students at the College
      of Veterinary Medicine, Michigan State University. Veterinary technology students
      are novice learners in nutrition who prefer visual, applied, and experiential
      modes of instruction. The program uses the American College of Veterinary
      Nutrition's "Circle of Nutrition," concept maps, and case-based delivery and
      assessment.

PMID- 18723818
TI  - Resident and graduate training in veterinary nutrition.
AB  - Training programs for veterinarians seeking board certification by the American
      College of Veterinary Nutrition (ACVN) are structured in one of two ways: (1) as
      programs similar to specialty training in other clinical disciplines or (2) as
      graduate programs leading to advanced degrees combined with clinical training.
      Residency training occurs through a variety of approaches, including didactic
      coursework, case-based and applied learning, clinical training, teaching,
      research, and self-study. Challenges to successful residency and graduate
      training include low numbers of diplomates, particularly at veterinary schools;
      low numbers of applicants; small numbers of funded programs; and faculty
      promotion systems that do not reward residency or graduate training and program
      development. The mentoring of individuals seeking both board certification and a
      graduate degree presents additional considerations, including recruitment of
      individuals motivated in research and structuring a combined program that
      facilitates completion of both tasks in a timely fashion.

PMID- 18723819
TI  - SPIKE and D-PIKE: innovative experiences that engage students early and position
      them to succeed in food-supply veterinary medicine.
AB  - Recent trends in urbanization of the population, increased need for bio-security
      on large farms, and more food-animal or mixed-animal practitioners approaching
      retirement age are forcing a renewed focus on recruiting and training veterinary
      students with an interest in production-animal medicine. The increasing number of
      veterinary students coming from urban backgrounds has led to a need to expose
      these students to standard animal-production practices and to interest them in a
      career involving food animals. This article describes one such program developed
      at Iowa State University, in which 14 students obtained hands-on experience in
      all aspects of swine and dairy production across a wide sampling of herd size,
      housing style, bio-security levels, and production phases. The participating
      students, ranging from senior undergraduates to third-year veterinary students,
      gained valuable insight not only into daily farming practices but also the
      knowledge and skills necessary to provide quality veterinary care to these
      clients. The first year of this program has yielded positive feedback from all
      participants, including the veterinary practices, private producers, corporate
      sponsors, and students. Current applicants cite positive comments from past
      participants as motivating their interest in the program. This program has the
      potential to expand as an opportunity to educate selected students in the field
      of food-supply veterinary medicine and to help fill the anticipated void in this
      area.

PMID- 18723820
TI  - Historical profile of gender in Turkish veterinary education.
AB  - Women in Turkey were first given the opportunity to attend schools of higher
      education in 1914. Following the establishment of the Turkish Republic in 1923, a
      number of social, judicial, and economic reforms took place that enabled women to
      participate actively in both the public and private sectors, and, as a
      consequence, the number of women students in higher education increased rapidly.
      The first woman graduated from the veterinary school in Ankara in 1935, becoming
      the first female veterinarian in the country. Since that time, the number of
      female veterinary graduates in Turkey has steadily increased.

PMID- 18723821
TI  - Comparison of student performance after lecture-based and case-based/problem
      based teaching in a large group.
AB  - The purpose of this study was to compare traditional lecture-based (LB) and case
      based/problem-based (CB/PB) learning in a large group. Year 3 veterinary students
      at Kansas State University were asked to participate in a randomized controlled
      study. Students were grouped and randomly assigned to be taught by a CB/PB or a
      LB method. Students took identical multiple-choice examinations, one given within
      a week of the last class and a different one given four months later. There was
      no direct effect of teaching method on group scores for either examination. CB/PB
      students scored higher on higher-difficulty questions on the first examination (p
      < 0.003), but there was no effect on questions of lower and medium difficulty.
      There was no effect of teaching method on student performance for the second
      examination; however, the question difficulty category scores were all different
      (p < 0.017). Evaluation of examination scores suggests that the two teaching
      methods were of similar efficacy.

PMID- 18723822
TI  - Development and evaluation of an online computer-aided learning (CAL) package to
      promote small-animal welfare.
AB  - RATIONALE FOR THE STUDY: The aims of the study, conducted as a student research
      project in the 2004-5 session, were to develop an interactive, online computer
      aided learning (CAL) package on the topic of small-animal husbandry; to validate
      the resource as a suitable lecture replacement for first-year veterinary
      students; and to raise awareness of current guidelines and legislation relating
      to small-animal housing among local catteries and kennels and in the wider
      community. METHODOLOGY: Quantitative feedback was collected from student and
      teaching staff using paper-based questionnaires. Qualitative feedback was
      gathered from open questionnaire responses and through focus-group discussions
      with students. Student examination marks were compared for 2004 and 2005,
      allowing a comparison of student performance before and after the replacement of
      the traditional lecture with the CAL package. Ethical approval for the study was
      granted by the faculty's Ethics Committee. RESULTS AND CONCLUSIONS: The CAL
      package on small-animal housing was well received by teaching staff and students;
      student performance in examinations improved after the introduction of the CAL
      program, suggesting that it provides a suitable alternative to didactic teaching.
      The creation and distribution of the CAL package on CD-ROM and its availability
      via the Internet are intended to contribute to small-animal welfare education in
      local catteries and kennels and further afield. The package sets a precedent for
      the development of more Internet-based, student-authored CAL packages in the
      future, providing additional resources for independent learning.

PMID- 18723824
TI  - Knock down of Caenorhabditis elegans cutc-1 exacerbates the sensitivity toward
      high levels of copper.
AB  - Copper, though toxic in excess, is an essential trace element that serves as a
      cofactor in many critical biological processes such as respiration, iron
      transport, and oxidative stress protection. To maintain this balance between
      requirement and toxicity, biological systems have developed intricate systems
      allowing the preservation of homeostasis while ensuring delivery of copper to the
      appropriate cellular component. The nematode Caenorhabditis elegans was exploited
      to assess the effects of copper toxicity at the population level to identify key
      changes in life cycle traits including, lethality, brood size, generation time,
      growth, and life span. To enhance our understanding of the complexities of copper
      homeostasis at the genetic level, the expression profile and functional
      significance of a putative copper cytoplasmic metallochaperone cutc-1 were
      analyzed. Using quantitative PCR technology, cutc-1 was found to be downregulated
      with increasing CuSO(4) concentrations. However, although total (whole body)
      copper levels increased in nematodes exposed to elevated levels of copper, wild
      type and knock down of cutc-1 by RNA-mediated interference (RNAi) were
      statistically indistinguishable. Nevertheless, RNAi of cutc-1 affected brood
      size, growth and induced a marked increase in protruding vulva and bagging
      phenotypes at higher copper exposures. This indicates that cutc-1 plays a crucial
      role in the protection from excess copper.

PMID- 18723823
TI  - Coassembly of different sulfonylurea receptor subtypes extends the phenotypic
      diversity of ATP-sensitive potassium (KATP) channels.
AB  - K(ATP) channels are metabolic sensors and targets of potassium channel openers
      (KCO; e.g., diazoxide and pinacidil). They comprise four sulfonylurea receptors
      (SUR) and four potassium channel subunits (Kir6) and are critical in regulating
      insulin secretion. Different SUR subtypes (SUR1, SUR2A, SUR2B) largely determine
      the metabolic sensitivities and the pharmacological profiles of K(ATP) channels.
      SUR1- but not SUR2-containing channels are highly sensitive to metabolic
      inhibition and diazoxide, whereas SUR2 channels are sensitive to pinacidil. It is
      generally believed that SUR1 and SUR2 are incompatible in channel coassembly. We
      used triple tandems, T1 and T2, each containing one SUR (SUR1 or SUR2A) and two
      Kir6.2Delta26 (last 26 residues are deleted) to examine the coassembly of
      different SUR. When T1 or T2 was expressed in Xenopus laevis oocytes, small whole
      cell currents were activated by metabolic inhibition (induced by azide) plus a
      KCO (diazoxide for T1, pinacidil for T2). When coexpressed with any SUR subtype,
      the activated-currents were increased by 2- to 13-fold, indicating that different
      SUR can coassemble. Consistent with this, heteromeric SUR1+SUR2A channels were
      sensitive to azide, diazoxide, and pinacidil, and their single-channel burst
      duration was 2-fold longer than that of the T1 channels. Furthermore, SUR2A was
      coprecipitated with SUR1. Using whole-cell recording and immunostaining,
      heteromeric channels could also be detected when T1 and SUR2A were coexpressed in
      mammalian cells. Finally, the response of the SUR1+SUR2A channels to azide was
      found to be intermediate to those of the homomeric channels. Therefore, different
      SUR subtypes can coassemble into K(ATP) channels with distinct metabolic
      sensitivities and pharmacological profiles.

PMID- 18723825
TI  - Induction of hepatic glutathione S-transferases in male mice by prototypes of
      various classes of microsomal enzyme inducers.
AB  - The underlying need for glutathione S-transferase (Gst) induction is thought to
      be an adaptive response to chemical stress within the cell. Classical microsomal
      enzyme inducers (MEIs) increase the expression of biotransformation enzymes
      (phase I and II) and transporters through transcription factors, such as the aryl
      hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X
      receptor (PXR), peroxisome proliferator-activated receptor (PPAR) alpha, and
      nuclear factor erythroid-derived 2-related factor 2 (Nrf2). The effects of MEIs
      on the induction of hepatic Gsts in mice have not been comprehensively
      characterized. The purpose of this study was to determine the effects of 15 MEIs
      on the mRNA expression of 19 mouse Gsts. Male C57BL/6 mice were treated with
      three different activators each for AhR, CAR, PXR, PPARalpha, and Nrf2. In
      general, the Gsts are readily induced. All five transcription factors appear to
      play a role in Gst induction. The Nrf2 activators induced most Gsts (10),
      followed by the CAR, PXR, and PPARalpha activators (6-7), whereas the AhR ligands
      induced the least (1). Clofibrate, a PPARalpha agonist, induced most of the Gsts;
      however, all three PPARalpha agonists decreased Gstp1/2 mRNA. None of the 15
      inducers was able to increase or only minimally increased eight of the Gsts
      (Gsta3, Gstk1, Gstm6, Gsto1, Gstp1/2, Gstt3, Gstz1, and MGst1). Thus, the
      protection afforded by a ligand for one of these transcription factors will
      depend on the activator, as well as which Gst that detoxifies the chemicals of
      interest.

PMID- 18723826
TI  - Estimates of cancer potency of 2,3,4,7,8-pentachlorodibenzofuran using both
      nonlinear and linear approaches.
AB  - Cancer potency estimates were derived for 2,3,4,7,8-pentachlorodibenzofuran (4
      PeCDF) using data collected from the recently published National Toxicology
      Program bioassay in female Sprague-Dawley rats. By using a toxicokinetic model
      for 4-PeCDF, the dose-response relationship for combined liver tumors
      (hepatocellular adenomas and cholangiocarcinomas) in rats was assessed in terms
      of lifetime average liver concentration and lifetime average adipose
      concentration with data from both the lifetime and the stop-exposure components
      of the bioassay. Benchmark dose modeling was performed to estimate tissue
      concentrations at two points of departure (EC(10) and EC(01) and their 95% upper
      and lower confidence limits). The same toxicokinetic model with human input
      values was then used to back-extrapolate human equivalent doses that corresponded
      to the internal tissue concentration measures at the points of departure.
      Information regarding the cancer mode of action was used to support the
      development of several toxicity criterion values based on a nonlinear method,
      e.g., reference dose or tolerable daily intake. Nonlinear estimates of toxicity
      criteria based on observed noncancer toxic events as possible precursors to tumor
      formation were also derived and were similar in value to those based on combined
      liver tumors. For comparison purposes, linear estimates of cancer potency were
      also derived.

PMID- 18723827
TI  - Cigarette smoke condensate enhances respiratory syncytial virus-induced chemokine
      release by modulating NF-kappa B and interferon regulatory factor activation.
AB  - Exposure to cigarette smoke is a risk factor contributing to the severity of
      respiratory tract infections associated with respiratory syncytial virus (RSV).
      Stimulation of airway epithelial cells by either RSV or cigarette smoke
      condensate (CSC) has been shown to induce secretion of the proinflammatory
      chemokines. However, the effect of coexposure of airway epithelial cells to CSC
      and RSV on inducible chemokine production has not been previously investigated.
      The results of this study indicate that CSC costimulation significantly increased
      RSV-induced interleukin-8 (IL-8) and monocyte chemoattactant protein-1 gene and
      protein expression when compared with each stimulus alone. Promoter deletion
      studies identified the interferon stimulatory response element (ISRE) of the IL-8
      promoter as a critical region responsible for the synergistic increase of IL-8
      gene transcription during mixed exposure. CSC costimulation enhanced RSV-induced
      activation of interferon regulatory factor (IRF)-1 and IRF-7, which bind to the
      ISRE site. CSC also furthered RSV-induced activation of the transcription factor
      nuclear factor kappa B (NF-kappaB), as shown by increased NF-kappaB DNA binding
      to its specific site of the IL-8 promoter and increased NF-kappaB-driven gene
      transcription. Therefore, our data demonstrate that a combined exposure to CSC
      and RSV synergistically increases chemokine expression in airway epithelial
      cells, suggesting that CSC contributes to an exuberant immune response to RSV by
      stimulating overlapping signal transduction pathways.

PMID- 18723828
TI  - Suppression of the p53-dependent replicative senescence response by
      lysophosphatidic acid signaling.
AB  - Lysophosphatidic acid (LPA) is a lipid mediator of a large number of biological
      processes, including wound healing, brain development, vascular remodeling, and
      tumor progression. Its role in tumor progression is probably linked to its
      ability to induce cell proliferation, migration, and survival. In particular, the
      ascites of ovarian cancers is rich in LPA and has been implicated in growth and
      invasion of ovarian tumor cells. LPA binds to specific G protein-coupled
      receptors and thereby activates multiple signal transduction pathways, including
      those initiated by the small GTPases Ras, Rho, and Rac. We report here a genetic
      screen with retroviral cDNA expression libraries to identify genes that allow
      bypass of the p53-dependent replicative senescence response in mouse neuronal
      cells, conditionally immortalized by a temperature-sensitive mutant of SV40 large
      T antigen. Using this approach, we identified the LPA receptor type 2 (LPA(2))
      and the Rho-specific guanine nucleotide exchange factor Dbs as potent inducers of
      senescence bypass. Enhanced expression of LPA(2) or Dbs also results in
      senescence bypass in primary mouse embryo fibroblasts in the presence of wild
      type p53, in a Rho GTPase-dependent manner. Our results reveal a novel and
      unexpected link between LPA signaling and the p53 tumor-suppressive pathway.

PMID- 18723829
TI  - SIRT1 contributes in part to cisplatin resistance in cancer cells by altering
      mitochondrial metabolism.
AB  - Tumors frequently develop resistance to cisplatin, a platinum drug used as a
      cornerstone of present-day chemotherapy regimens, significantly decreasing its
      usefulness in the clinic. Although it is known that cisplatin-resistant (CP-r)
      cancer cells commonly grow more slowly and exhibit reduced uptake of various
      compounds, including nutrients, the effect of tumor metabolism on cisplatin
      resistance is unclear. It was found that in CP-r cells, uptake of 2-deoxyglucose
      was reduced due to dysfunction and altered morphology of mitochondria compared
      with cisplatin-sensitive parental cancer cells. The CP-r cells overexpressed
      SIRT1, a histone deacetylase that plays a central role in DNA damage response and
      transcriptional silencing. Incubation of drug-sensitive cells in low glucose
      medium induced the expression of SIRT1 and increased cellular resistance to
      cisplatin. Reduced SIRT1 expression by a SIRT1 SMART small interfering RNA duplex
      sensitized the >20-fold resistant CP-r cells to cisplatin treatment 1.5- to 2
      fold, and SIRT1 overexpression by SIRT1 cDNA transfection increased cisplatin
      resistance in cisplatin-sensitive cells by 2- to 3-fold. Our findings therefore
      suggest that reduced glucose use and altered mitochondrial metabolism mediated by
      SIRT1 is one of several alterations that contribute to cellular resistance to
      cisplatin.

PMID- 18723830
TI  - Promoter hypermethylation of the p16 gene is associated with poor prognosis in
      recurrent early-stage hepatocellular carcinoma.
AB  - Despite significant advances in the detection and treatment of hepatocellular
      carcinoma, the prognosis of patients with hepatocellular carcinoma remains very
      poor, in part due to the high incidence of recurrence. This study was aimed at
      identifying a prognostic indicator of recurrence in patients with hepatocellular
      carcinoma. We retrospectively analyzed CpG island hypermethylation of the p14,
      p15, p16, GSTP1, integrin alpha4, SYK, and CDH1 genes in fresh-frozen tissues
      from 265 patients with hepatocellular carcinoma using the methylation-specific
      PCR. The expression levels of p16 and p53 were evaluated by immunohistochemistry.
      CpG island hypermethylation was detected in 6% for p14, 21% for p15, 67% for p16,
      75% for GSTP1, 23% for integrin alpha4, 12% for SYK, and 57% for CDH1. Recurrence
      was observed in 102 (38%) of the 265 patients. There was no association between
      the risk for recurrence and hypermethylation of any gene studied. However, p16
      methylation was associated with a poor survival after surgery for recurrent stage
      I to II hepatocellular carcinomas (hazard ratio, 4.05; 95% confidence interval,
      1.15-14.20; P = 0.03). In addition, the hazard of failure after recurrence was
      about 3.80 (95% confidence interval, 1.03-14.20; P = 0.04) times higher in
      patients with p16 methylation than in those without. Negative expression of p16
      at a protein level was also associated with poor survival in recurrent stage I to
      II hepatocellular carcinomas, but p53 expression did not have a synergistic
      effect on the poor prognosis. In conclusion, the present study suggests that p16
      methylation may be associated with a poor prognosis in recurrent early-stage
      hepatocellular carcinomas.

PMID- 18723831
TI  - Platelet chemokines in vascular disease.
AB  - Platelets are a rich source of different chemokines and express chemokine
      receptors. CXCL4 is highly abundant in platelets and involved in promoting
      monocyte arrest from rolling and monocyte differentiation to macrophages. CXCL4
      can also associate with CCL5 and amplify its effect on monocytes. The
      megakaryocyte CXCL7 gene product is proteolytically cleaved into the strong
      neutrophil chemoattractant, NAP-2, which has also been implicated in repair cell
      homing to vascular lesions. Platelet adhesion can induce release of CCL2 and
      CXCL8 from endothelial cells. Conversely, the chemokines CCL17, CCL22, and CXCL12
      made by other cells amplify platelet activation. Platelet chemokines enhance
      recruitment of various hematopoietic cells to the vascular wall, fostering
      processes such as neointima formation, atherosclerosis, and thrombosis, but also
      vessel repair and regeneration after vascular injury.

PMID- 18723832
TI  - Mutagenesis from meiotic recombination is not a primary driver of sequence
      divergence between Saccharomyces species.
AB  - Local rates of recombination positively correlate with DNA sequence diversity in
      many species. To test whether this relationship stems from mutagenicity of
      meiotic recombination, studies often look for a similar association between local
      rates of recombination and sequence "divergence" between species. Because
      recombination is mutagenic in yeast, I evaluate this assay by testing whether
      noncoding DNA sequence divergence between Saccharomyces species is related to
      measures of meiotic double-strand DNA breaks or crossover rates derived from
      Saccharomyces cerevisiae. Contrary to expectation, I find that sequence
      divergence is either uncorrelated or negatively correlated with rates of both
      double-strand break and crossover. Several caveats are mentioned, but these
      results suggest that mutagenesis from meiotic recombination is not the primary
      driver of sequence divergence between Saccharomyces species. This study
      demonstrates that the association between interspecies nucleotide divergence and
      local recombination rates is not always a reliable indicator of recombination's
      mutagenicity.

PMID- 18723833
TI  - The linkage between deviant lifestyles and victimization: an examination from a
      life course perspective.
AB  - A small but growing body of research has demonstrated the merits of linking
      victimization to a life course perspective. Although cross-sectional studies have
      shown a strong association between deviant lifestyles and victimization, few have
      assessed this association from the life course perspective. Drawing data from a
      prospective, longitudinal study, the current study examines this association in a
      group of high school adolescents. Results from latent growth curve models show
      that (a) victimization and deviant lifestyles, measured as involvement in
      delinquent activities, affiliation with deviant peers, and time spent on
      unsupervised activities change over time; and (b) change in deviant lifestyle
      patterns leads to change in victimization patterns over time.

PMID- 18723834
TI  - Comment on 'electron holography on dynamic motion of secondary electrons around
      sciatic nerve tissues'.
AB  - We present an alternative interpretation of the holographic phase dislocation
      loops revealed by Shindo et al. [J. Electron Microsc. 56(1): 1-5 (2007)] around a
      charged sample. Our interpretation does not involve the motion of secondary
      electrons around a charged object. It relates, instead, to fluctuating charges on
      the sample and to the resulting Moire-type patterns in the hologram.

PMID- 18723835
TI  - Compartmental analysis of plasma and liver n-3 essential fatty acids in alcohol
      dependent men during withdrawal.
AB  - The mechanism by which chronic ethanol consumption reduces concentrations of long
      chain polyunsaturated (LCP) fatty acids (FA) in tissues of humans was
      investigated in alcohol-dependent (AD) men during early withdrawal and to a well
      matched control group by fitting the concentration-time curves of d(5)-labeled n
      3 FA from plasma and liver, which originated from an oral dose of d(5)-linolenic
      acid (d(5)-18:3n-3) ethyl ester to a compartmental model. Blood sampled over 168
      h and a liver specimen obtained 96 h after isotope administration were analyzed
      for d(5)-18:3n-3, d(5)-20:5n-3, d(5)-22:5n-3, and d(5)-22:6n-3. Plasma 20:5n-3
      and 22:5n-3 were lower in AD subjects, compared with controls (20:5n-3: -50%,
      22:5n-3: -34%). Increased amounts of d(5)-18:3n-3 were directed toward synthesis
      of d(5)-20:5n-3 in AD subjects (P < .05). However, this effect was offset by
      larger amounts of 20:5n-3 lost from plasma (control: 2.0 vs. AD: 4.2 mg d(-1)).
      In livers of AD subjects, more d(5)-18:3n-3 and d(5)-22:5n-3 were utilized for
      synthesis of d(5)-20:5n-3 (+200%) and d(5)-22:6n-3 (+210%), respectively, than
      was predicted from plasma kinetics. Although, the potential to utilize linolenic
      acid for synthesis of LCP FA was greater in AD subjects compared with controls,
      heightened disappearance rates of 20:5n-3 reduced overall plasma concentrations
      of several endogenous n-3 LCP FA.

PMID- 18723836
TI  - Training in cognitive behavioral therapy in psychiatry residency: an overview for
      educators.
AB  - In January 2001, Accreditation Council of Graduate Medical Education accredited
      general psychiatry training programs were charged with the requirement to train
      residents in cognitive-behavioral therapy (CBT) to a level of competence.
      Programs were given the responsibility to delineate standards for trainees, to
      determine measures of competence, and to provide remediation for deficiencies in
      performance. Effective education in CBT in general and child and adolescent
      psychiatry residency training can be more successful when educators understand
      the barriers to implementation of empirically supported therapies (ESTs). Robust
      training programs in CBT must take into account cultural barriers to
      psychotherapy training and the educational demands placed on residents in adult
      and child and adolescent psychiatry. Resources for training and evaluation
      materials are available to training directors and teachers.

PMID- 18723837
TI  - Disseminating evidence-based practices for adults with PTSD and severe mental
      illness in public-sector mental health agencies.
AB  - Posttraumatic stress disorder (PTSD) remains largely untreated among adults with
      severe mental illnesses (SMI). The treatment of psychotic symptoms usually takes
      precedence in the care of adults with SMI. Such oversight is problematic in that
      PTSD in SMI populations is common (19%-43%), contributes a significant illness
      burden, and hinders mental health care. Yet few public-sector mental health
      agencies routinely provide specialized services for PTSD. The purpose of the
      article is to describe strategies and efforts to disseminate trauma-focused
      empirically based practices in a public-sector mental health system. Identified
      challenges include limited resources and commitment; knowledge deficits,
      attitudes, and biases; and limited practice accountability at provider, facility,
      and system levels. Proposed strategies for overcoming these challenges are to set
      clear goals, nurture broad-based organizational commitment and key stakeholder
      involvement, implement specialty training efforts to provide information and
      change attitudes, provide ongoing supervision, conduct fidelity monitoring, and
      ensure accountability to the extent possible.

PMID- 18723838
TI  - Implementation of evidence-based services for youth: assessing provider
      knowledge.
AB  - Although provider knowledge is a potential barrier in the dissemination of
      evidence-based services for youth, research in this area is currently limited by
      a lack of instrumentation. The present study examined the utility of the
      Knowledge of Evidence-Based Services Questionnaire (KEBSQ), a 40-item self-report
      measure designed to assess reporter knowledge of evidence-based practices (EBPs)
      in the treatment of youth psychopathology. The KEBSQ items encompass practice
      elements identified in both empirically supported and unsupported protocols used
      in the treatment of four prevalent childhood problem areas: anxious/avoidant,
      depressed/withdrawn, disruptive behavior, and attention/hyperactivity. Findings
      from the present investigation lend support for the basic psychometric properties
      of the KEBSQ. Results supported temporal stability, discriminative validity, and
      sensitivity to training. Practical implications to the dissemination of EBPs,
      areas for future research, and limitations are discussed.

PMID- 18723839
TI  - Who drinks most of the total alcohol in young men--risky single occasion drinking
      as normative behaviour.
AB  - AIMS: The objectives of this study were to analyse (a) the distribution of risky
      single-occasion drinking (RSOD) among 19-year-old men in Switzerland and (b) to
      show the percentage of all alcohol consumption in the form of RSOD. METHODS: The
      study was based on a census of Swiss francophone 19-year-old men consecutively
      reporting for processing. The study was conducted at Army Recruitment Center. The
      participants were 4116 recruits consecutively enrolling for mandatory army
      recruitment procedures between 23 January and 29 August in 2007. The measures
      were alcohol consumption measured in drinks of approximately 10 g of pure
      alcohol, number of drinking occasions with six or more drinks (RSOD) in the past
      12 months and a retrospective 1 week drinking diary. RESULTS: 264 recruits were
      never seen by the research staff, 3536 of the remaining 3852 conscripts completed
      a questionnaire which showed that 7.2% abstained from alcohol and 75.5% of those
      drinking had an RSOD day at least monthly. The typical frequency of drinking was
      1-3 days per week on weekends. The average quantity on weekends was about seven
      drinks, 69.3% of the total weekly consumption was in the form of RSOD days, and
      of all the alcohol consumed, 96.2% was by drinkers who had RSOD days at least
      once a month. CONCLUSION: Among young men, RSOD constitutes the norm. Prevention
      consequently must address the total population and not only high-risk drinkers.

PMID- 18723840
TI  - What is causing the reduced drug-placebo difference in recent schizophrenia
      clinical trials and what can be done about it?
AB  - On September 18, 2007, a collaborative session between the International Society
      for CNS Clinical Trials and Methodology and the International Society for CNS
      Drug Development was held in Brussels, Belgium. Both groups, with membership from
      industry, academia, and governmental and nongovernmental agencies, have been
      formed to address scientific, clinical, regulatory, and methodological challenges
      in the development of central nervous system therapeutic agents. The focus of
      this joint session was the apparent diminution of drug-placebo differences in
      recent multicenter trials of antipsychotic medications for schizophrenia. To
      characterize the nature of the problem, some presenters reported data from
      several recent trials that indicated higher rates of placebo response and lower
      rates of drug response (even to previously established, comparator drugs), when
      compared with earlier trials. As a means to identify the possible causes of the
      problem, discussions covered a range of methodological factors such as
      participant characteristics, trial designs, site characteristics, clinical
      setting (inpatient vs outpatient), inclusion/exclusion criteria, and diagnostic
      specificity. Finally, possible solutions were discussed, such as improving
      precision of participant selection criteria, improving assessment instruments
      and/or assessment methodology to increase reliability of outcome measures,
      innovative methods to encourage greater subject adherence and investigator
      involvement, improved rater training and accountability metrics at clinical sites
      to increase quality assurance, and advanced methods of
      pharmacokinetic/pharmacodynamic modeling to optimize dosing prior to initiating
      large phase 3 trials. The session closed with a roundtable discussion and
      recommendations for data sharing to further explore potential causes and viable
      solutions to be applied in future trials.

PMID- 18723841
TI  - Gene-environment interplay between cannabis and psychosis.
AB  - Cannabis use is considered a contributory cause of schizophrenia and psychotic
      illness. However, only a small proportion of cannabis users develop psychosis.
      This can partly be explained by the amount and duration of the consumption of
      cannabis and by its strength but also by the age at which individuals are first
      exposed to cannabis. Genetic factors, in particular, are likely to play a role in
      the short- and the long-term effects cannabis may have on psychosis outcome. This
      review will therefore consider the interplay between genes and exposure to
      cannabis in the development of psychotic symptoms and schizophrenia. Studies
      using genetic, epidemiological, experimental, and observational techniques will
      be discussed to investigate gene-environment correlation gene-environment
      interaction, and higher order interactions within the cannabis-psychosis
      association. Evidence suggests that mechanisms of gene-environment interaction
      are likely to underlie the association between cannabis and psychosis. In this
      respect, multiple variations within multiple genes--rather than single genetic
      polymorphisms--together with other environmental factors (eg, stress) may
      interact with cannabis to increase the risk of psychosis. Further research on
      these higher order interactions is needed to better understand the biological
      pathway by which cannabis use, in some individuals, may cause psychosis in the
      short- and long term.

PMID- 18723843
TI  - Mechanism of cancer cell adaptation to metabolic stress: proteomics
      identification of a novel thyroid hormone-mediated gastric carcinogenic signaling
      pathway.
AB  - Gastric cancer is the second most common cancer worldwide and has a poor
      prognosis. To determine the mechanism of adaptation to metabolic stress in cancer
      cells, we used gastric cancer as a model system to reveal the potential signaling
      pathways involved. Two-dimensional polyacrylamide gel electrophoresis coupled
      with ESI-Q-TOF MS/MS analysis was used to identify differentially expressed
      proteins between gastric tumor tissues and the corresponding noncancerous
      tissues. In total, 107 spots with significant alteration (+/-over 2-fold, p <
      0.05) were positively identified by MS/MS analysis. Altered expression of
      representative proteins was validated by RT-PCR and Western blotting. Cluster
      analysis of the changed proteins revealed an interesting group of metabolic
      proteins, which suggested accumulation of triiodothyronine (T(3); the major
      functional component of thyroid hormone) and overexpression of hypoxia-induced
      factor (HIF) in gastric carcinoma. These observations were further confirmed by
      electrochemiluminescence immunoassay and immunohistochemistry. T(3)-induced
      expression of HIF1-alpha and vascular endothelial growth factor was further
      verified using a gastric cancer cell line and in vivo mouse model. Because the
      early accumulation of HIF1-alpha was found to be independent of de novo
      transcription, we also found that the cytosolic cascade phosphatidylinositol 3
      kinase/Akt pathway sensitive to T(3) stimulus was involved. Furthermore we
      demonstrated that T(3)-induced overexpression of HIF1-alpha was mediated by
      fumarate accumulation and could be enhanced by fumarate hydratase inactivation
      but inhibited by 2-oxoglutarate. These results provide evidence for alteration of
      metabolic proteins and dysfunction of thyroid hormone regulation in gastric
      tumors, and a novel thyroid hormone-mediated tumorigenic signaling pathway is
      proposed. Our findings are considered a significant step toward a better
      understanding of adaptations to metabolic stress in gastric carcinogenesis.

PMID- 18723842
TI  - Lysine acetylation is a highly abundant and evolutionarily conserved modification
      in Escherichia coli.
AB  - Lysine acetylation and its regulatory enzymes are known to have pivotal roles in
      mammalian cellular physiology. However, the extent and function of this
      modification in prokaryotic cells remain largely unexplored, thereby presenting a
      hurdle to further functional study of this modification in prokaryotic systems.
      Here we report the first global screening of lysine acetylation, identifying 138
      modification sites in 91 proteins from Escherichia coli. None of the proteins has
      been previously associated with this modification. Among the identified proteins
      are transcriptional regulators, as well as others with diverse functions.
      Interestingly, more than 70% of the acetylated proteins are metabolic enzymes and
      translation regulators, suggesting an intimate link of this modification to
      energy metabolism. The new dataset suggests that lysine acetylation could be
      abundant in prokaryotic cells. In addition, these results also imply that
      functions of lysine acetylation beyond regulation of gene expression are
      evolutionarily conserved from bacteria to mammals. Furthermore, we demonstrate
      that bacterial lysine acetylation is regulated in response to stress stimuli.

PMID- 18723844
TI  - Isolation and characterization of mAMSA-hypersensitive mutants. Cytotoxicity of
      Top2 covalent complexes containing DNA single strand breaks.
AB  - Topoisomerase II (Top2) is the primary target for active anti-cancer agents. We
      developed an efficient approach for identifying hypersensitive Top2 mutants and
      isolated a panel of mutants in yeast Top2 conferring hypersensitivity to the
      intercalator N-[4-(9-acridinylamino)-3-methoxyphenyl]methanesulphonanilide
      (mAMSA). Some mutants conferred hypersensitivity to etoposide as well as mAMSA,
      whereas other mutants exhibited hypersensitivity only to mAMSA. Two mutants in
      Top2, changing Pro(473) to Leu and Gly(737) to Val, conferred extraordinary
      hypersensitivity to mAMSA and were chosen for further characterization. The
      mutant proteins were purified, and their biochemical activities were assessed.
      Both mutants encode enzymes that are hypersensitive to inhibition by mAMSA and
      other intercalating agents and exhibited elevated levels of mAMSA-induced
      Top2:DNA covalent complexes. While Gly(737) --> Val Top2p generated elevated
      levels of Top2-mediated double strand breaks in vitro, the Pro(473) --> Leu
      mutant protein showed only a modest increase in Top2-mediated double strand
      breaks but much higher levels of Top2-mediated single strand breaks. In addition,
      the Pro(473) --> Leu mutant protein also generated high levels of mAMSA
      stabilized covalent complexes in the absence of ATP. We tested the role of single
      strand cleavage in cell killing with alleles of Top2 that could generate single
      strand breaks, but not double strand breaks. Expression in yeast of a Pro(473) -
      > Leu mutant that could only generate single strand breaks conferred
      hypersensitivity to mAMSA. These results indicate that generation of single
      strand breaks by Top2-targeting agents can be an important component of cell
      killing by Top2-targeting drugs.

PMID- 18723845
TI  - Structural analysis of a periplasmic binding protein in the tripartite ATP
      independent transporter family reveals a tetrameric assembly that may have a role
      in ligand transport.
AB  - Several bacterial solute transport mechanisms involve members of the periplasmic
      binding protein (PBP) superfamily that bind and deliver ligand to integral
      membrane transport proteins in the ATP-binding cassette, tripartite
      tricarboxylate transporter, or tripartite ATP-independent (TRAP) families. PBPs
      involved in ATP-binding cassette transport systems have been well characterized,
      but only a few PBPs involved in TRAP transport have been studied. We have
      measured the thermal stability, determined the oligomerization state by small
      angle x-ray scattering, and solved the x-ray crystal structure to 1.9 A
      resolution of a TRAP-PBP (open reading frame tm0322) from the hyperthermophilic
      bacterium Thermotoga maritima (TM0322). The overall fold of TM0322 is similar to
      other TRAP transport related PBPs, although the structural similarity of backbone
      atoms (2.5-3.1 A root mean square deviation) is unusually low for PBPs within the
      same group. Individual monomers within the tetrameric asymmetric unit of TM0322
      exhibit high root mean square deviation (0.9 A) to each other as a consequence of
      conformational heterogeneity in their binding pockets. The gel filtration elution
      profile and the small angle x-ray scattering analysis indicate that TM0322
      assembles as dimers in solution that in turn assemble into a dimer of dimers in
      the crystallographic asymmetric unit. Tetramerization has been previously
      observed in another TRAP-PBP (the Rhodobacter sphaeroides alpha-keto acid-binding
      protein) where quaternary structure formation is postulated to be an important
      requisite for the transmembrane transport process.

PMID- 18723847
TI  - Bilobar apical pseudoaneurysm after left ventricular venting in a Marfan's
      patient.
AB  - A Marfan patient presented with a bilobar apical pseudoaneurysm after repeated
      surgery. These abnormalities were demonstrated by three-dimensional-echo,
      Doppler, and CT-reconstruction. The pseudoaneurysm was related to an apical
      venting procedure. In this case, a conservative approach was chosen, although in
      general, pseudoaneurysms form an indication for operative correction, because of
      the risk of rupture and acute tamponade.

PMID- 18723846
TI  - Multiple mechanisms contribute to Schizosaccharomyces pombe origin recognition
      complex-DNA interactions.
AB  - Eukaryotic DNA replication requires the assembly of multiprotein pre-replication
      complexes (pre-RCs) at chromosomal origins of DNA replication. Here we describe
      the interactions of highly purified Schizosaccharomyces pombe pre-RC components,
      SpORC, SpCdc18, and SpCdt1, with each other and with ars1 origin DNA. We show
      that SpORC binds DNA in at least two steps. The first step likely involves
      electrostatic interactions between the AT-hook motifs of SpOrc4 and AT tracts in
      ars1 DNA and results in the formation of a salt-sensitive complex. In the second
      step, the salt-sensitive complex is slowly converted to a salt-stable complex
      that involves additional interactions between SpORC and DNA. Binding of SpORC to
      ars1 DNA is facilitated by negative supercoiling and is accompanied by changes in
      DNA topology, suggesting that SpORC-DNA complexes contain underwound or
      negatively writhed DNA. Purified human origin recognition complex (ORC) induces
      similar topological changes in origin DNA, indicating that this property of ORC
      is conserved in eukaryotic evolution and plays an important role in ORC function.
      We also show that SpCdc18 and SpCdt1 form a binary complex that has greater
      affinity for DNA than either protein alone. In addition, both proteins contribute
      significantly to the stability of the initial SpORC-DNA complex and enhance the
      SpORC-dependent topology changes in origin DNA. Thus, the formation of stable
      protein-DNA complexes at S. pombe origins of replication involves binary
      interactions among all three proteins, as well as interactions of both SpORC and
      SpCdt1-SpCdc18 with origin DNA. These findings demonstrate that SpORC is not the
      sole determinant of origin recognition.

PMID- 18723848
TI  - Transoesophageal echocardiographic diagnosis of pulmonary arteriovenous
      malformation in a patient with ischaemic stroke.
AB  - We report a case of an ischaemic stroke secondary to an isolated pulmonary
      arteriovenous malformation. In this case, transoesophageal echocardiogram played
      a pivotal role in shunt identification, exclusion of atrial septal defect, and
      definitive diagnosis and localization of the pulmonary arteriovenous
      malformations. Pulmonary arteriovenous malformations should be excluded in all
      patients with cryptogenic stroke.

PMID- 18723849
TI  - Comparison of myocardial contrast echocardiography derived myocardial perfusion
      reserve with invasive determination of coronary flow reserve.
AB  - AIMS: Invasive measurements of coronary flow reserve (CFR) by Doppler flow wire
      are an established method for determining coronary blood flow physiology.
      Myocardial contrast echocardiography (MCE) is a potential non-invasive method for
      quantifying myocardial blood flow (MBF). However, few studies have compared MCE
      derived myocardial perfusion reserve (MPR) with Doppler flow wire-derived CFR,
      measured simultaneously in human subjects. This study aimed to correlate MCE
      derived MPR with Doppler flow wire-derived CFR. METHODS AND RESULTS: Ten patients
      with at least two angiographically normal coronary arteries underwent
      simultaneous invasive Doppler flow wire measurements and MCE imaging at rest and
      at peak hyperaemia. Hyperaemia was induced by intravenous adenosine infusion.
      Doppler-derived CFR was calculated as the ratio of hyperaemic to baseline average
      peak red blood cell velocity. MPR was calculated as the hyperaemic to baseline
      ratio of the following parameters: myocardial blood volume (MBV), myocardial
      microbubble velocity (MMV), and MBF. MCE was performed using real-time and
      triggered imaging with contrast infused intravenously by bolus and continuous
      methods. Regardless of whether the contrast was infused by bolus or continuous
      methods, Doppler flow wire-derived CFR had a stronger correlation with MPR
      derived by MBV (r=0.8, P=0.05) than with MPR derived by microbubble velocity
      (r=0.3, P>0.05) or MBF (r=0.4, P>0.05). Real-time imaging with continuous
      infusion provided better correlation with CFR than triggered imaging methods or
      bolus administration. CONCLUSION: Myocardial perfusion reserve derived by real
      time infusion MBV measurements correlates with Doppler flow wire-derived CFR.
      Therefore, MPR may be a potential surrogate for Doppler flow wire-derived CFR in
      patients with angiographically normal coronary arteries.

PMID- 18723850
TI  - Stereotactic body radiation therapy in patients with pelvic recurrence from
      rectal carcinoma.
AB  - OBJECTIVE: To investigate the clinical applications of stereotactic body
      radiation therapy (SBRT) using the CyberKnife system for pelvic recurrence from
      rectal cancer with a focus on survival and toxicity. METHODS: Between 2002 and
      2006, 23 patients with recurrent rectal cancer were treated with SBRT at our
      institution. The median follow-up was 31 months. Sites of recurrence were pre
      sacral in seven patients and the pelvic wall in 16. SBRT doses ranged from 30 to
      51 Gy (median 39 Gy) and were delivered in three fractions. Response to treatment
      was assessed by computed tomography. Overall and local progression-free survival
      and toxicities were recorded. RESULTS: Four-year overall survival and local
      control rates were 24.9 and 74.3%, respectively. No prognostic factor was found
      to affect patient survival or local progression. One patient developed a severe
      radiation-related toxicity, but recovered completely after treatment.
      CONCLUSIONS: SBRT for pelvic recurrence was found to be comparable with other
      modalities with respect to overall survival and complication rates. Further
      studies are needed to confirm these preliminary results.

PMID- 18723851
TI  - Impaired arterial baroreflex function before nitrate-induced vasovagal syncope
      during head-up tilt test.
AB  - AIMS: The aim of this study was to evaluate arterial baroreflex control of heart
      rate immediately before head-up tilt test (HUT)-induced vasovagal syncope (VVS).
      METHODS AND RESULTS: We enrolled 97 otherwise healthy subjects with recurrent
      unexplained syncope. After 10 min of rest in supine position, they underwent a
      passive HUT potentiated with nitroglycerin administration after 20 min. Beat-to
      beat heart rate and systolic blood pressure were continuously recorded. Sequence
      method was used to measure two complementary parameters reflecting arterial
      baroreflex control of heart rate: the baroreflex sensitivity (BRS) and the
      baroreflex effectiveness index (BEI). Twenty-one patients fainted before nitrate
      administration (HUT+) and 37 after nitrate administration (NTG+). Immediately
      before syncope, the NTG+ patients showed significantly lower BRS values than
      those observed at the end of the test in the patients without syncope (5.5 +/-
      2.8 vs. 7.7 +/- 3.4 ms/mmHg; P = 0.004) and a significantly lower BEI (30 +/- 20%
      vs. 53 +/- 24%; P < 0.001). The HUT+ patients did not show any significant
      differences in BRS and BEI before syncope from the values observed during the
      corresponding tilt period in the other groups. CONCLUSION: A significant
      depression in BRS and BEI occurs immediately before syncope in patients who faint
      after nitrate administration, thus suggesting that arterial baroreflex
      dysfunction plays a role in mediating nitrate-induced VVS.

PMID- 18723853
TI  - Modified test statistics by inter-voxel variance shrinkage with an application to
      f MRI.
AB  - Functional magnetic resonance imaging (f MRI) is a noninvasive technique which is
      commonly used to quantify changes in blood oxygenation and flow coupled to
      neuronal activation. One of the primary goals of f MRI studies is to identify
      localized brain regions where neuronal activation levels vary between groups.
      Single voxel t-tests have been commonly used to determine whether activation
      related to the protocol differs across groups. Due to the generally limited
      number of subjects within each study, accurate estimation of variance at each
      voxel is difficult. Thus, combining information across voxels is desirable in
      order to improve efficiency. Here, we construct a hierarchical model and apply an
      empirical Bayesian framework for the analysis of group f MRI data, employing
      techniques used in high-throughput genomic studies. The key idea is to shrink
      residual variances by combining information across voxels and subsequently to
      construct an improved test statistic. This hierarchical model results in a
      shrinkage of voxel-wise residual sample variances toward a common value. The
      shrunken estimator for voxel-specific variance components on the group analyses
      outperforms the classical residual error estimator in terms of mean-squared
      error. Moreover, the shrunken test statistic decreases false-positive rates when
      testing differences in brain contrast maps across a wide range of simulation
      studies. This methodology was also applied to experimental data regarding a
      cognitive activation task.

PMID- 18723852
TI  - From enzyme to zymogen: engineering Vip2, an ADP-ribosyltransferase from Bacillus
      cereus, for conditional toxicity.
AB  - The adenosine diphosphate (ADP)-ribosyltransferase, Vip2 (vegetative insecticidal
      protein), from Bacillus cereus in combination with another protein from the same
      organism, Vip1, has insecticidal activity against western corn rootworm larvae.
      The Vip2 protein exerts its intracellular poisoning effect by modifying actin and
      preventing actin polymerization. Due to the nature of this toxin, expression of
      Vip2 in planta is lethal. In this work, we attempted to build an enzyme precursor
      (proenzyme, zymogen) that would silently reside in one biological system (e.g.
      plants or yeast) and be activated in the other (insect larvae). Our approach
      involved engineering a random propeptide library at the C-terminal end of Vip2
      and selecting for malfunctional enzyme variants in yeast. A selected proenzyme
      (proVip2) possesses reduced enzymatic activity as compared with the wild-type
      Vip2 protein, but remains a potent toxin toward rootworm larvae. In addition,
      upon analysis of the digestive fate of the engineered enzyme precursor in
      rootworm larvae, we demonstrated that 'zymogenized' Vip2 can be proteolytically
      activated by rootworm digestive enzyme machinery. This report represents an
      example of applying a protein engineering strategy for the creation of a plant
      tolerated, zymogen-like form of an otherwise toxic protein. This approach may
      outline a novel path to address challenges associated with utilizing toxic
      proteins in certain biotechnological applications.

PMID- 18723854
TI  - An overview of the use of extremity dosemeters in some European countries for
      medical applications.
AB  - Some medical applications are associated with high doses to the extremities of
      the staff exposed to ionising radiation. At workplaces in nuclear medicine,
      interventional radiology, interventional cardiology and brachytherapy,
      extremities can be the limiting organs as far as regulatory dose limits for
      workers are concerned. However, although the need for routine extremity
      monitoring is clear for these applications, no data about the status of routine
      extremity monitoring reported by different countries was collected and analysed
      so far, at least at a European level. In this article, data collected from seven
      European countries are presented. They are compared with extremity doses
      extracted from dedicated studies published in the literature which were reviewed
      in a previous publication. The analysis shows that dedicated studies lead to
      extremity doses significantly higher than the reported doses, suggesting that
      either the most exposed workers are not monitored, or the dosemeters are not
      routinely worn or not worn at appropriate positions.

PMID- 18723855
TI  - Development, implementation and quality assurance of biokinetic models within
      CONRAD.
AB  - The work of the Task Group 5.2 'Research Studies on Biokinetic Models' of the
      CONRAD project is presented. New biokinetic models have been implemented by
      several European institutions. Quality assurance procedures included
      intercomparison of the results as well as quality assurance of model formulation.
      Additionally, the use of the models was examined leading to proposals of tuning
      parameters. Stable isotope studies were evaluated with respect to their
      implications to the new models, and new biokinetic models were proposed on the
      basis of their results. Furthermore, the development of a biokinetic model
      describing the effects of decorporation of actinides by
      diethylenetriaminepentaacetic acid treatment was initiated.

PMID- 18723856
TI  - Validation of the index of consciousness during sevoflurane and remifentanil
      anaesthesia: a comparison with the bispectral index and the cerebral state index.
AB  - BACKGROUND: The purpose of this study was to validate a new level of
      consciousness monitor derived from the EEG, called the index of consciousness
      (IoC), by comparing it with the bispectral index (BIS) and the cerebral state
      index (CSI) during general anaesthesia for cardiac surgery using sevoflurane,
      remifentanil, and atracurium. METHODS: After ethical committee approval and
      written patient consent, data from 35 patients [31 males, four females, age 55
      (10) yr] were recorded during general anaesthesia for elective cardiac bypass
      surgery. All patients were induced with sevoflurane 8%, until the Observer's
      Assessment of Alertness and Sedation (OAAS) scale level 1 was reached, and then
      was set at a 1% end-tidal sevoflurane concentration. Subsequently, remifentanil
      and atracurium were administered, the trachea was intubated, and the procedure
      continued as usual. To assess accuracy, the prediction probability (Pk) was
      calculated both during induction and during maintenance. RESULTS: The Pk values
      [mean (se)] for IoC, BIS, and CSI during induction were 0.90 (0.01), 0.90 (0.01),
      and 0.88 (0.01), respectively, whereas the corresponding Pk values during
      maintenance were 0.95 (0.01), 0.94 (0.01), and 0.60 (0.01). CONCLUSIONS: The
      three indices performed equally well during the induction phase and were able to
      predict the level of consciousness of the patients satisfactorily. During
      maintenance, the IoC and the BIS showed good agreement with the clinical signs.
      The CSI was significantly influenced by the administration of atracurium;
      therefore, the agreement with the OAAS scale during the maintenance phase was
      significantly less for CSI than for IoC and BIS.

PMID- 18723857
TI  - Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates:
      secondary results from the NEOPAIN trial.
AB  - BACKGROUND: Relationships between plasma morphine concentrations and neonatal
      responses to endotracheal tube (ETT) suctioning are unknown in preterm neonates.
      METHODS: Ventilated preterm neonates (n=898) from 16 centres were randomly
      assigned to placebo (n=449) or morphine (n=449). After an i.v. loading dose (100
      microg kg(-1)), morphine infusions [23-26 weeks postmenstrual age (PMA) 10 microg
      kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); and 30-32 weeks 30 microg kg(
      1) h(-1)] were established for a maximum of 14 days. Open-label morphine (20-100
      microg kg(-1)) was given for pain or agitation. Morphine assay and neonatal
      response to ETT suctioning was measured at 20-28 and 70-76 h after starting the
      drug infusion and at 10-14 h after discontinuation of the study drug. The
      concentration-effect response was investigated using non-linear mixed effects
      models. RESULTS: A total of 5119 data points (1598 measured morphine
      concentrations and 3521 effect measures) were available from 875 neonates for
      analysis. Clearance was 50% that of the mature value at 54.2 weeks PMA
      (CLmat(50)) and increased from 2.05 litre h(-1) 70 kg(-1) at 24 weeks PMA to 6.04
      litre h(-1) 70 kg(-1) at 32 weeks PMA. The volume of distribution in preterm
      neonates was 190 litre 70 kg(-1) (CV 51%) and did not change with age. There was
      no relationship between morphine concentrations (range 0-440 microg litre(-1))
      and heart rate changes associated with ETT suctioning or with the Premature
      Infant Pain Profile. CONCLUSIONS: A sigmoid curve describing maturation of
      morphine clearance is moved to the right in preterm neonates and volume of
      distribution is increased compared with term neonates. Morphine does not alter
      the neonatal response to ETT suctioning.

PMID- 18723858
TI  - Mitochondrial processes are impaired in hereditary inclusion body myopathy.
AB  - Hereditary inclusion body myopathy (HIBM) is an adult onset, slowly progressive
      distal and proximal myopathy. Although the causing gene, GNE, encodes for a key
      enzyme in the biosynthesis of sialic acid, its primary function in HIBM remains
      unknown. To elucidate the pathological mechanisms leading from the mutated GNE to
      the HIBM phenotype, we attempted to identify and characterize early occurring
      downstream events by analyzing the genomic expression patterns of muscle
      specimens from 10 HIBM patients carrying the M712T Persian Jewish founder
      mutation and presenting mild histological changes, compared with 10 healthy
      matched control individuals, using GeneChip expression microarrays. When
      analyzing the expression profile data sets by the intersection of three statistic
      methods (Student's t-test, TNoM and Info score), we found that the HIBM-specific
      transcriptome consists of 374 differentially expressed genes. The specificity of
      the HIBM transcriptome was assessed by the minimal transcript overlap found
      between HIBM and the transcriptome of nine additional muscle disorders including
      adult onset limb girdle myopathies, inflammatory myopathies and early onset
      conditions. A strikingly high proportion (18.6%) of the overall differentially
      expressed mRNAs of known function were found to encode for proteins implicated in
      various mitochondrial processes, revealing mitochondria pathways dysregulation.
      Mitochondrial morphological analysis by video-rate confocal microscopy showed a
      high degree of mitochondrial branching in cells of HIBM patients. The subtle
      involvement of mitochondrial processes identified in HIBM reveals an unexpected
      facet of HIBM pathophysiology which could at least partially explain the slow
      evolution of this disorder and give new insights in the disease mechanism.

PMID- 18723859
TI  - Genetic and physical interaction between the NPHP5 and NPHP6 gene products.
AB  - Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease, caused
      by mutations of at least nine different genes. Several extrarenal manifestations
      characterize this disorder, including cerebellar defects, situs inversus and
      retinitis pigmentosa. While the clinical manifestations vary significantly in
      NPHP, mutations of NPHP5 and NPHP6 are always associated with progressive
      blindness. This clinical finding suggests that the gene products, nephrocystin-5
      and nephrocystin-6, participate in overlapping signaling pathways to maintain
      photoreceptor homeostasis. To analyze the genetic interaction between these two
      proteins in more detail, we studied zebrafish embryos after depletion of NPHP5
      and NPHP6. Knockdown of zebrafish zNPHP5 and zNPHP6 produced similar phenotypes,
      and synergistic effects were observed after the combined knockdown of zNPHP5 and
      zNPHP6. The N-terminal domain of nephrocystin-6-bound nephrocystin-5, and mapping
      studies delineated the interacting site from amino acid 696 to 896 of NPHP6. In
      Xenopus laevis, knockdown of NPHP5 caused substantial neural tube closure
      defects. This phenotype was copied by expression of the nephrocystin-5-binding
      fragment of nephrocystin-6, and rescued by co-expression of nephrocystin-5,
      supporting a physical interaction between both gene products in vivo. Since the N
      and C-terminal fragments of nephrocystin-6 engage in the formation of homo- and
      heteromeric protein complexes, conformational changes seem to regulate the
      interaction of nephrocystin-6 with its binding partners.

PMID- 18723860
TI  - Pollination systems of Colchicum (Colchicaceae) in southern Africa: evidence for
      rodent pollination.
AB  - BACKGROUND AND AIMS: Plants adapted for pollination by rodents tend to exhibit a
      distinct floral syndrome that includes dull coloured and geoflorous
      inflorescences and nocturnal anthesis and nectar production. On the basis of
      their floral traits, it was predicted that two African Colchicum species (C.
      scabromarginatum and C. coloratum) are rodent-pollinated. METHODS: Field studies
      were carried out in the semi-arid Succulent Karoo region of South Africa. Live
      trapping of rodents was conducted and pollen loads on the rodents were
      quantified. The daily periodicity of nectar production was determined. Selective
      exclusion and controlled pollination experiments were also conducted. KEY
      RESULTS: Live-trapped rodents were found to carry large amounts of Colchicum
      pollen on the fur of their snouts, and in their faeces. Birds were occasional
      pollinators of flowers of C. coloratum. During the evening, nectar volume and
      concentration increased for both species. When vertebrates were excluded from C.
      scabromarginatum and C. coloratum plants, there was a significant decrease in
      seed set compared with open control plants. By contrast, vertebrate exclusion did
      not significantly affect seed production of a congener, C. hantamense, which has
      floral traits associated with insect pollination. Breeding system experiments
      revealed that both C. scabromarginatum and C. coloratum require pollinators for
      seed production. Colchicum scabromarginatum is strictly self-incompatible,
      whereas C. coloratum is partially self-compatible. CONCLUSIONS: Pollination by
      rodents occurs in two African Colchicum species. C. scabromarginatum appears to
      depend exclusively on rodents for seed production, while birds and autonomous
      selfing may contribute to seed production in C. coloratum. These are the first
      records of rodent pollination in the Colchicaceae.

PMID- 18723861
TI  - Morphological and AFLP-based differentiation within the taxonomical complex
      section Caninae (subgenus Rosa).
AB  - BACKGROUND AND AIMS: The taxonomical structure of the polymorphic subgenus Rosa
      section Caninae is highly complex due to the combination of some unusual
      features: the unique polyploid chromosomal constitution, the heterogamic canina
      meiosis, the ability to hybridize interspecifically, and the predominantly
      matroclinal inheritance. Although most taxonomists agree on the subdivision of
      the section into three morphologically well-defined groups (Rubigineae, Vestitae,
      and Caninae), they disagree on the existence of smaller groups such as
      Tomentellae. The aim was to gain insight in the taxonomical structure and
      investigate the interpopulation differentiation of the polymorphic section
      Caninae by analysing morphological and AFLP-based characters of the seven most
      common Belgian dog-rose taxa. METHODS: The intersubsectional and -specific
      relationships within the dog-roses were examined using morphological and
      molecular-genetic markers. AFLP data were analysed with basic descriptive genetic
      statistics because of the lack of Hardy-Weinberg equilibrium due to the polyploid
      genetic structure and heterogamic meiosis. KEY RESULTS: Both the morphological
      and AFLP-based analyses supported the subdivision of the dog-roses in three well
      defined though partly overlapping groups, Rubigineae, Vestitae and Caninae.
      However, it was not possible to distinguish between the morphologically well
      defined taxa within the same subsection using AFLP-based data. In addition, the
      results suggested a high similarity of Rosa balsamica with subsection Caninae
      taxa. Small-scale geographical AFLP-based differentiation was observed within
      several dog-rose taxa. Surprisingly, individuals sampled at one locality and
      belonging to morphologically distinct dog-rose taxa displayed higher genetic
      similarities in comparison to their congeners sampled at different localities.
      CONCLUSIONS: The hybridogenic character of the dog-roses was reflected in the
      vague boundaries between the subsections and on the species level within the
      subsections. Indications were found for current or historical hybridization on
      the genetic structure of the population. No morphological or AFLP-based evidence
      was obtained to support the existence of the separate subsection Tomentellae.

PMID- 18723862
TI  - Home versus day rehabilitation: a randomised controlled trial.
AB  - OBJECTIVE: to assess the effect of home versus day rehabilitation on patient
      outcomes. DESIGN: randomised controlled trial. SETTING: post-hospital
      rehabilitation. PARTICIPANTS: two hundred and twenty-nine hospitalised patients
      referred for ambulatory rehabilitation. INTERVENTIONS: hospital-based day
      rehabilitation programme versus home-based rehabilitation programme. MAIN OUTCOME
      MEASURES: at 3 months, information was collected on hospital readmission,
      transfer to residential care, functional level, quality of life, carer stress and
      carer quality of life. At 6 months, place of residence, hospital re-admissions
      and mortality status were collected. RESULTS: there were significant improvements
      in the functional outcomes from baseline to 3 months for all participants. At
      discharge, carers of patients in day hospital reported higher Caregiver Strain
      Index (CSI) scores in comparison to home rehabilitation carers (4.95 versus 3.56,
      P = 0.047). Patients in day hospital had double the risk of readmission compared
      to those in home rehabilitation (RR = 2.1; 95% CI 1.2-3.9). This effect persisted
      at 6 months. CONCLUSIONS: day hospital patients are more likely to be readmitted
      to hospital possibly due to increased access to admitting medical staff. This
      small trial favours the home as a better site for post-hospital rehabilitation.

PMID- 18723864
TI  - Estimating the risk of exposure of British livestock to foot-and-mouth disease
      associated with the importation of ship and aircraft waste.
AB  - A quantitative risk assessment model was developed to estimate the frequency with
      which meat waste from ships or aircraft might expose British livestock to
      infection with foot-and-mouth disease (fmd), and investigate the factors that
      might contribute to the risk. In the model, the total weight of waste introduced
      that was contaminated with fmd was estimated to be 26 kg per year, with 90 per
      cent certainty that it would be between 10 and 53 kg. As a result, it was
      estimated that there would be a mean of 1429 years between outbreaks of fmd due
      to ship and aircraft waste, with a 90 per cent certainty that the interval would
      be between 500 and 10,000 years. These estimates were affected by three principal
      uncertainties: first, the prevalence of fmd; secondly, the probability of the
      waste being removed and fed to pigs; and thirdly, the probability that overboard
      dumping of contaminated waste might expose livestock to fmd. The effect of these
      uncertainties on the model was investigated in a sensitivity analysis.

PMID- 18723863
TI  - Pharmacokinetics of ertapenem in critically ill patients with acute renal failure
      undergoing extended daily dialysis.
AB  - BACKGROUND: Extended (daily) dialysis (EDD) is an increasingly popular mode of
      renal replacement therapy in the ICU (intensive care unit) as it combines the
      advantages of intermittent haemodialysis (IHD) and continuous renal replacement
      therapy (CRRT), i.e. excellent detoxification accompanied by cardiovascular
      tolerability. The aim of this study was to evaluate pharmacokinetics (PK) of
      ertapenem, the newest carbapenem with once-daily dosing, in critically ill
      patients with anuric acute renal failure (ARF) undergoing EDD. PATIENTS AND
      METHODS: In a single-centre, prospective, open-label study six ICU patients with
      ARF undergoing EDD were treated with 1 g ertapenem given as a single intravenous
      dose. EDD was performed using a high-flux dialyzer (polysulphone, 1.3 m(2)).
      Blood and dialysate flow were 160 mL/min, and the length of treatment was 480
      min. Plasma samples were collected at different time-points up to 24 h after
      medication. Drug concentrations were determined by a validated LC-MS method. Free
      drug concentrations were estimated using a two-class binding site equation.
      RESULTS: After a single dose of 1000 mg free ertapenem, protein-unbound plasma
      concentrations exceeded a MIC(90) value of 2 mg/L for >20 h after dosing. The
      clearance of the tested dialyzer was 38.5 +/- 14.2 mL/min. CONCLUSIONS: In
      contrast to patients undergoing regular IHD, in which a dose reduction is
      required, our data suggest that in patients treated with EDD a standard dose of
      ertapenem (1 g/day), i.e. dose for patients without renal failure, is required to
      maintain adequate plasma drug levels.

PMID- 18723865
TI  - Data quality of animal health records on Swiss dairy farms.
AB  - High-quality data are essential for veterinary surveillance systems, and their
      quality can be affected by the source and the method of collection. Data recorded
      on farms could provide detailed information about the health of a population of
      animals, but the accuracy of the data recorded by farmers is uncertain. The aims
      of this study were to evaluate the quality of the data on animal health recorded
      on 97 Swiss dairy farms, to compare the quality of the data obtained by different
      recording systems, and to obtain baseline data on the health of the animals on
      the 97 farms. Data on animal health were collected from the farms for a year.
      Their quality was evaluated by assessing the completeness and accuracy of the
      recorded information, and by comparing farmers' and veterinarians' records. The
      quality of the data provided by the farmers was satisfactory, although electronic
      recording systems made it easier to trace the animals treated. The farmers tended
      to record more health-related events than the veterinarians, although this varied
      with the event considered, and some events were recorded only by the
      veterinarians. The farmers' attitude towards data collection was positive.
      Factors such as motivation, feedback, training, and simplicity and
      standardisation of data collection were important because they influenced the
      quality of the data.

PMID- 18723866
TI  - Outbreak of canine distemper in domestic ferrets (Mustela putorius furo).
AB  - In 2006 an outbreak of canine distemper affected 14 young domestic ferrets in
      Barcelona, Spain. Their clinical signs included a reduced appetite, lethargy,
      dyspnoea, coughing, sneezing, mucopurulent ocular and nasal discharges, facial
      and perineal dermatitis, diarrhoea, splenomegaly and fever. Late in the course of
      the disease, general desquamation and pruritus, and hyperkeratotic/crusting
      dermatitis of the lips, eyes, nose, footpads, and perineal area were observed.
      None of the ferrets developed neurological signs. Non-regenerative anaemia and
      high serum concentrations of alpha- and beta-globulins were the most common
      laboratory findings. Most of the animals died or were euthanased because of
      respiratory complications. Postmortem there were no signs of lung collapse.
      Distemper was diagnosed by direct immunofluorescence of conjunctival swabs or pcr
      of several organs, and histology revealed the characteristic eosinophilic
      intracytoplasmic and intranuclear inclusion bodies of canine distemper virus in
      several organs. The minimum incubation periods calculated for six of the ferrets
      were 11 to 56 days, and in 13 of the ferrets the signs of disease lasted 14 to 34
      days. Inclusion bodies compatible with infection by herpesvirus were found in the
      lungs of one of the ferrets.

PMID- 18723867
TI  - Tetracycline-resistant Chlamydia suis isolates in Italy.

PMID- 18723868
TI  - Congenital pseudomyotonia in Chianina cattle.

PMID- 18723869
TI  - Canine leishmaniosis in the UK.

PMID- 18723870
TI  - Vaccination against bluetongue.

PMID- 18723871
TI  - Time for a rethink on the ban on swill feeding?

PMID- 18723872
TI  - Representing the profession.

PMID- 18723873
TI  - Estrogens and Alzheimer's disease: is cholesterol a link?

PMID- 18723874
TI  - Dendritic vasopressin release: reducing the flow makes blood vessels grow.

PMID- 18723875
TI  - Signaling pathways involved in sphingosine kinase activation and sphingosine-1
      phosphate release in rat myometrium in late pregnancy: role in the induction of
      cyclooxygenase 2.
AB  - We investigated the regulation of the sphingosine kinase (SphK)/sphingosine-1
      phosphate (S1P) axis and its role during pregnancy in the rat myometrium. SphK1
      and SphK2 were coexpressed in myometrium during gestation. The levels and
      activity of SphK1/2 were modest at midgestation (d 12), increased at d 19 and
      progressively declined to low at postpartum. Similar patterns were observed for
      the phosphorylation of ERK and protein kinase C (PKC). Inhibition of PKC and ERK
      reduced SphK1/2 activity. In late pregnancy, levels of cyclooxygenase 2 (COX2)
      increased in parallel to SphK levels. Using a pharmacological approach, we
      demonstrated that in primary cultures of myometrial cells from d-19 pregnant
      rats, induction of COX2 was mediated by 4beta-phorbol 12,13-dibutyrate and IL
      1beta through sequential activation of PKC, ERK1/2, and SphK1. S1P produced by
      SphK1 was released in the medium. Addition of S1P, IL-1beta or 4beta-phorbol
      12,13-dibutyrate enhanced COX2 levels via Gi protein. Interestingly, S1P was also
      released by myometrial tissues at late gestation. This event was dependent on
      PKC/ERK/SphK1. By contrast, in d-12 myometrial tissues, the release of S1P was
      markedly reduced in association with low levels of SphK1 and COX2. However,
      prolonged incubation of myometrium from midgestation led to the induction of
      COX2. This effect was blocked by SphK inhibitors, providing evidence of the close
      relationship between SphK activity and COX2 induction in rat myometrium. Overall,
      our findings provided insight into the physiological relevance of the SphK
      activation and S1P release in uterine smooth muscle during gestation.

PMID- 18723876
TI  - Endocrine-related resources from the national institutes of health.

PMID- 18723877
TI  - Metabolism of the tumor angiogenesis inhibitor 4-(N-(S
      Glutathionylacetyl)amino)phenylarsonous acid.
AB  - 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (GSAO) is a small,
      synthetic mitochondrial poison that targets angiogenic endothelial cells and is
      currently being tested in a Phase I/IIa clinical trial. The trivalent arsenical
      of GSAO reacts with and perturbs adenine nucleotide translocase of the inner
      mitochondrial membrane of endothelial cells, which leads to proliferation arrest.
      Three observations indicated that the gamma-glutamyl residue of GSAO is cleaved
      at the endothelial cell surface by gamma-glutamyl transpeptidase (gammaGT). GSAO
      was found to be an efficient substrate for gammaGT, endothelial cell accumulation
      and antiproliferative activity of GSAO was blunted by a competitive substrate and
      an active site inhibitor of gammaGT, and the level of cell surface gammaGT
      correlated strongly with the sensitivity of cells to GSAO. Using transport
      inhibitors, it was revealed that the resulting metabolite of GSAO cleavage by
      gammaGT, 4-(N-(S-cysteinylglycylacetyl)amino) phenylarsonous acid (GCAO), was
      transported across the plasma membrane by an organic anion transporter.
      Furthermore, GCAO is likely processed by dipeptidases in the cytosol to 4-(N-(S
      cysteinylacetyl)amino) phenylarsonous acid (CAO), and it is this metabolite that
      reacts with mitochondrial adenine nucleotide translocase. Taken together, our
      findings indicate that gammaGT processing of GSAO at the cell surface is the rate
      limiting step in its antiangiogenic activity. This information can explain the
      kidney toxicity at high doses of GSAO noted in preclinical studies and will aid
      in the anticipation of potential side effects in humans and in the design of
      better antimitochondrial cancer drugs.

PMID- 18723879
TI  - UBIQUITIN-SPECIFIC PROTEASE 26 is required for seed development and the
      repression of PHERES1 in Arabidopsis.
AB  - The Arabidopsis mutant Atubp26 initiates autonomous endosperm at a frequency of
      approximately 1% in the absence of fertilization and develops arrested seeds at a
      frequency of approximately 65% when self-pollinated. These phenotypes are similar
      to those of the FERTILIZATION INDEPENDENT SEED (FIS) class mutants, mea, fis2,
      fie, and Atmsi1, which also show development of the central cell into endosperm
      in the absence of fertilization and arrest of the embryo following fertilization.
      Atubp26 results from a T-DNA insertion in the UBIQUITIN-SPECIFIC PROTEASE gene
      AtUBP26, which catalyzes deubiquitination of histone H2B and is required for
      heterochromatin silencing. The paternal copy of AtUBP26 is able to complement the
      loss of function of the maternal copy in postfertilization seed development. This
      contrasts to the fis class mutants where the paternal FIS copy does not rescue
      aborted seeds. As in the fis class mutants, the Polycomb group (PcG) complex
      target gene PHERES1 (PHE1) is expressed at higher levels in Atubp26 ovules than
      in wild type; there is a lower level of H3K27me3 at the PHE1 locus. The
      phenotypes suggest that AtUBP26 is required for normal seed development and the
      repression of PHE1.

PMID- 18723878
TI  - The pleiotropic phenotype of Apc mutations in the mouse: allele specificity and
      effects of the genetic background.
AB  - Familial adenomatous polyposis (FAP) is a human cancer syndrome characterized by
      the development of hundreds to thousands of colonic polyps and extracolonic
      lesions including desmoid fibromas, osteomas, epidermoid cysts, and congenital
      hypertrophy of the pigmented retinal epithelium. Afflicted individuals are
      heterozygous for mutations in the APC gene. Detailed investigations of mice
      heterozygous for mutations in the ortholog Apc have shown that other genetic
      factors strongly influence the phenotype. Here we report qualitative and
      quantitative modifications of the phenotype of Apc mutants as a function of three
      genetic variables: Apc allele, p53 allele, and genetic background. We have found
      major differences between the Apc alleles Min and 1638N in multiplicity and
      regionality of intestinal tumors, as well as in incidence of extracolonic
      lesions. By contrast, Min mice homozygous for either of two different knockout
      alleles of p53 show similar phenotypic effects. These studies illustrate the
      classic principle that functional genetics is enriched by assessing penetrance
      and expressivity with allelic series. The mouse permits study of an allelic gene
      series on multiple genetic backgrounds, thereby leading to a better understanding
      of gene action in a range of biological processes.

PMID- 18723880
TI  - Genetic basis of sex-specific color pattern variation in Drosophila
      malerkotliana.
AB  - Pigmentation is a rapidly evolving trait that can play important roles in
      mimicry, sexual selection, thermoregulation, and other adaptive processes in many
      groups of animals. In Drosophila, pigmentation can differ dramatically among
      closely related taxa, presenting a good opportunity to dissect the genetic
      changes underlying species divergence. In this report, we investigate the genetic
      basis of color pattern variation between two allopatric subspecies of Drosophila
      malerkotliana, a widespread member of the ananassae species subgroup. In D.
      malerkotliana malerkotliana, the last three abdominal segments are darkly
      pigmented in males but not in females, while in D. malerkotliana pallens both
      sexes lack dark pigmentation. Composite interval mapping in F2 hybrid progeny
      shows that this difference is largely controlled by three quantitative trait loci
      (QTL) located on the 2L chromosome arm, which is homologous to the 3R of D.
      melanogaster (Muller element E). Using highly recombinant introgression strains
      produced by repeated backcrossing and phenotypic selection, we show that these
      QTL do not correspond to any of the candidate genes known to be involved in
      pigment patterning and synthesis in Drosophila. These results, in combination
      with similar analyses in other Drosophila species, indicate that different
      genetic and molecular changes are responsible for the evolution of similar
      phenotypic traits in different lineages. This feature makes Drosophila color
      patterns a powerful model for investigating how the genetic basis of trait
      evolution is influenced by the intrinsic organization of regulatory pathways
      controlling the development of these traits.

PMID- 18723881
TI  - Increase in quantitative variation after exposure to environmental stresses
      and/or introduction of a major mutation: G x E interaction and epistasis or
      canalization?
AB  - Why does phenotypic variation increase upon exposure of the population to
      environmental stresses or introduction of a major mutation? It has usually been
      interpreted as evidence of canalization (or robustness) of the wild-type
      genotype; but an alternative population genetic theory has been suggested by J.
      Hermisson and G. Wagner: "the release of hidden genetic variation is a generic
      property of models with epistasis or genotype-environment interaction." In this
      note we expand their model to include a pleiotropic fitness effect and a direct
      effect on residual variance of mutant alleles. We show that both the genetic and
      environmental variances increase after the genetic or environmental change, but
      these increases could be very limited if there is strong pleiotropic selection.
      On the basis of more realistic selection models, our analysis lends further
      support to the genetic theory of Hermisson and Wagner as an interpretation of
      hidden variance.

PMID- 18723882
TI  - Quantitative trait loci mapping of genome regions controlling permethrin
      resistance in the mosquito Aedes aegypti.
AB  - The mosquito Aedes aegypti is the principal vector of dengue and yellow fever
      flaviviruses. Permethrin is an insecticide used to suppress Ae. aegypti adult
      populations but metabolic and target site resistance to pyrethroids has evolved
      in many locations worldwide. Quantitative trait loci (QTL) controlling permethrin
      survival in Ae. aegypti were mapped in an F(3) advanced intercross line. Parents
      came from a collection of mosquitoes from Isla Mujeres, Mexico, that had been
      selected for permethrin resistance for two generations and a reference permethrin
      susceptible strain originally from New Orleans. Following a 1-hr permethrin
      exposure, 439 F(3) adult mosquitoes were phenotyped as knockdown resistant,
      knocked down/recovered, or dead. For QTL mapping, single nucleotide polymorphisms
      (SNPs) were identified at 22 loci with potential antixenobiotic activity
      including genes encoding cytochrome P450s (CYP), esterases (EST), or glutathione
      transferases (GST) and at 12 previously mapped loci. Seven antixenobiotic genes
      mapped to chromosome I, six to chromosome II, and nine to chromosome III. Two QTL
      of major effect were detected on chromosome III. One corresponds with a SNP
      previously associated with permethrin resistance in the para sodium channel gene
      and the second with the CCEunk7o esterase marker. Additional QTL but of
      relatively minor effect were also found. These included two sex-linked QTL on
      chromosome I affecting knockdown and recovery and a QTL affecting survival and
      recovery. On chromosome II, one QTL affecting survival and a second affecting
      recovery were detected. The patterns confirm that mutations in the para gene
      cause target-site insensitivity and are the major source of permethrin resistance
      but that other genes dispersed throughout the genome contribute to recovery and
      survival of mosquitoes following permethrin exposure.

PMID- 18723883
TI  - Sequencing and comparative analysis of a conserved syntenic segment in the
      Solanaceae.
AB  - Comparative genomics is a powerful tool for gaining insight into genomic function
      and evolution. However, in plants, sequence data that would enable detailed
      comparisons of both coding and noncoding regions have been limited in
      availability. Here we report the generation and analysis of sequences for an
      unduplicated conserved syntenic segment (CSS) in the genomes of five members of
      the agriculturally important plant family Solanaceae. This CSS includes a 105-kb
      region of tomato chromosome 2 and orthologous regions of the potato, eggplant,
      pepper, and petunia genomes. With a total neutral divergence of 0.73-0.78
      substitutions/site, these sequences are similar enough that most noncoding
      regions can be aligned, yet divergent enough to be informative about evolutionary
      dynamics and selective pressures. The CSS contains 17 distinct genes with
      generally conserved order and orientation, but with numerous small-scale
      differences between species. Our analysis indicates that the last common ancestor
      of these species lived approximately 27-36 million years ago, that more than one
      third of short genomic segments (5-15 bp) are under selection, and that more than
      two-thirds of selected bases fall in noncoding regions. In addition, we identify
      genes under positive selection and analyze hundreds of conserved noncoding
      elements. This analysis provides a window into 30 million years of plant
      evolution in the absence of polyploidization.

PMID- 18723884
TI  - Three alpha-subunits of heterotrimeric G proteins and an adenylyl cyclase have
      distinct roles in fruiting body development in the homothallic fungus Sordaria
      macrospora.
AB  - Sordaria macrospora, a self-fertile filamentous ascomycete, carries genes
      encoding three different alpha-subunits of heterotrimeric G proteins (gsa, G
      protein Sordaria alpha subunit). We generated knockout strains for all three gsa
      genes (Deltagsa1, Deltagsa2, and Deltagsa3) as well as all combinations of double
      mutants. Phenotypic analysis of single and double mutants showed that the genes
      for Galpha-subunits have distinct roles in the sexual life cycle. While single
      mutants show some reduction of fertility, double mutants Deltagsa1Deltagsa2 and
      Deltagsa1Deltagsa3 are completely sterile. To test whether the pheromone
      receptors PRE1 and PRE2 mediate signaling via distinct Galpha-subunits, two
      recently generated Deltapre strains were crossed with all Deltagsa strains.
      Analyses of the corresponding double mutants revealed that compared to GSA2, GSA1
      is a more predominant regulator of a signal transduction cascade downstream of
      the pheromone receptors and that GSA3 is involved in another signaling pathway
      that also contributes to fruiting body development and fertility. We further
      isolated the gene encoding adenylyl cyclase (AC) (sac1) for construction of a
      knockout strain. Analyses of the three DeltagsaDeltasac1 double mutants and one
      Deltagsa2Deltagsa3Deltasac1 triple mutant indicate that SAC1 acts downstream of
      GSA3, parallel to a GSA1-GSA2-mediated signaling pathway. In addition, the
      function of STE12 and PRO41, two presumptive signaling components, was
      investigated in diverse double mutants lacking those developmental genes in
      combination with the gsa genes. This analysis was further completed by expression
      studies of the ste12 and pro41 transcripts in wild-type and mutant strains. From
      the sum of all our data, we propose a model for how different Galpha-subunits
      interact with pheromone receptors, adenylyl cyclase, and STE12 and thus
      cooperatively regulate sexual development in S. macrospora.

PMID- 18723885
TI  - Tissue-specific defects are caused by loss of the Drosophila MAN1 LEM domain
      protein.
AB  - The nuclear lamina represents a protein network required for nuclear structure
      and function. One family of lamina proteins is defined by an approximately 40-aa
      LAP2, Emerin, and MAN1 (LEM) domain (LEM-D) that binds the nonspecific DNA
      binding protein, barrier-to-autointegration factor (BAF). Through interactions
      with BAF, LEM-D proteins serve as a bridge between chromosomes and the nuclear
      envelope. Mutations in genes encoding LEM-D proteins cause human laminopathies
      that are associated with tissue-restricted pathologies. Drosophila has five genes
      that encode proteins with LEM homology. Using yeast two-hybrid analyses, we
      demonstrate that four encode proteins that bind Drosophila (d)BAF. In addition to
      dBAF, dMAN1 associates with lamins, the LEM-D protein Bocksbeutel, and the
      receptor-regulated Smads, demonstrating parallel protein interactions with
      vertebrate homologs. P-element mobilization was used to generate null dMAN1
      alleles. These mutants showed decreased viability, with surviving adults
      displaying male sterility, decreased female fertility, wing patterning and
      positioning defects, flightlessness, and locomotion difficulties that became more
      severe with age. Increased phospho-Smad staining in dMAN1 mutant wing discs is
      consistent with a role in transforming growth factor (TGF)-beta/bone morphogenic
      protein (BMP) signaling. The tissue-specific, age-enhanced dMAN1 mutant
      phenotypes are reminiscent of human laminopathies, suggesting that studies in
      Drosophila will provide insights into lamina dysfunction associated with disease.

PMID- 18723886
TI  - The multiple-wing-hairs gene encodes a novel GBD-FH3 domain-containing protein
      that functions both prior to and after wing hair initiation.
AB  - The frizzled signaling/signal transduction pathway controls planar cell polarity
      (PCP) in both vertebrates and invertebrates. Epistasis experiments argue that in
      the Drosophila epidermis multiple wing hairs (mwh) acts as a downstream component
      of the pathway. The PCP proteins accumulate asymmetrically in pupal wing cells
      where they are thought to form distinct protein complexes. One is located on the
      distal side of wing cells and a second on the proximal side. This asymmetric
      protein accumulation is thought to lead to the activation of the cytoskeleton on
      the distal side, which in turn leads to each cell forming a single distally
      pointing hair. We identified mwh as CG13913, which encodes a novel G protein
      binding domain-formin homology 3 (GBD-FH3) domain protein. The Mwh protein
      accumulated on the proximal side of wing cells prior to hair formation. Unlike
      planar polarity proteins such as Frizzled or Inturned, Mwh also accumulated in
      growing hairs. This suggested that mwh had two temporally separate functions in
      wing development. Evidence for these two functions also came from temperature
      shift experiments with a temperature-sensitive allele. Overexpression of Mwh
      inhibited hair initiation, thus Mwh acts as a negative regulator of the
      cytoskeleton. Our data argued early proximal Mwh accumulation restricts hair
      initiation to the distal side of wing cells and the later hair accumulation of
      Mwh prevents the formation of ectopic secondary hairs. This later function
      appears to be a feedback mechanism that limits cytoskeleton activation to ensure
      a single hair is formed.

PMID- 18723887
TI  - The dominant cold-sensitive Out-cold mutants of Drosophila melanogaster have
      novel missense mutations in the voltage-gated sodium channel gene paralytic.
AB  - Here we report the molecular characterization of Out-cold (Ocd) mutants of
      Drosophila melanogaster, which produce a dominant, X-linked, cold-sensitive
      paralytic phenotype. From its initial 1.5-Mb cytological location within 13F1
      16A2, P-element and SNP mapping reduced the Ocd critical region to <100 kb and to
      six candidate genes: hangover, CG9947, CG4420, eIF2a, Rbp2, and paralytic (para).
      Complementation testing with para null mutations strongly suggests Ocd and para
      are allelic, as does gene rescue of Ocd semilethality with a wild-type para
      transgene. Pesticide resistance and electrophysiological phenotypes of Ocd
      mutants support this conclusion. The para gene encodes a voltage-gated sodium
      channel. Sequencing the Ocd lines revealed mutations within highly conserved
      regions of the para coding sequence, in the transmembrane segment S6 of domain
      III (I1545M and T1551I), and in the linker between domains III and IV (G1571R),
      the location of the channel inactivation gate. The G1571R mutation is of
      particular interest as mutations of the orthologous residue (G1306) in the human
      skeletal muscle sodium channel gene SCN4A are associated with cases of periodic
      paralysis and myotonia, including the human cold-sensitive disorder paramyotonia
      congenita. The mechanisms by which sodium channel mutations cause cold
      sensitivity are not well understood. Therefore, in the absence of suitable
      vertebrate models, Ocd provides a system in which genetic, molecular,
      physiological, and behavioral tools can be exploited to determine mechanisms
      underlying sodium channel periodic paralyses.

PMID- 18723888
TI  - HP1 is distributed within distinct chromatin domains at Drosophila telomeres.
AB  - Telomeric regions in Drosophila are composed of three subdomains. A chromosome
      cap distinguishes the chromosome end from a DNA double-strand break; an array of
      retrotransposons, HeT-A, TART, and TAHRE (HTT), maintains telomere length by
      targeted transposition to chromosome ends; and telomere-associated sequence
      (TAS), which consists of a mosaic of complex repeated sequences, has been
      identified as a source of gene silencing. Heterochromatin protein 1 (HP1) and HP1
      ORC-associated protein (HOAP) are major protein components of the telomere cap in
      Drosophila and are required for telomere stability. Besides the chromosome cap,
      HP1 is also localized along the HTT array and in TAS. Mutants for Su(var)205, the
      gene encoding HP1, have decreased the HP1 level in the HTT array and increased
      transcription of individual HeT-A elements. This suggests that HP1 levels
      directly affect HeT-A activity along the HTT array, although they have little or
      no effect on transcription of a white reporter gene in the HTT. Chromatin
      immunoprecipitation to identify other heterochromatic proteins indicates that TAS
      and the HTT array may be distinct from either heterochromatin or euchromatin.

PMID- 18723889
TI  - Sex-biased lethality or transmission of defective transcription machinery in
      Arabidopsis.
AB  - Unlike animals, whose gametes are direct products of meiosis, plant meiotic
      products undergo additional rounds of mitosis, developing into multicellular
      haploid gametophytes that produce egg or sperm cells. The complex development of
      gametophytes requires extensive expression of the genome, with DNA-dependent RNA
      polymerases I, II, and III being the key enzymes for nuclear gene expression. We
      show that loss-of-function mutations in genes encoding key subunits of RNA
      polymerases I, II, or III are not transmitted maternally due to the failure of
      female megaspores to complete the three rounds of mitosis required for the
      development of mature gametophytes. However, male microspores bearing defective
      polymerase alleles develop into mature gametophytes (pollen) that germinate, grow
      pollen tubes, fertilize wild-type female gametophytes, and transmit the mutant
      genes to the next generation at moderate frequency. These results indicate that
      female gametophytes are autonomous with regard to gene expression, relying on
      transcription machinery encoded by their haploid nuclei. By contrast, male
      gametophytes make extensive use of transcription machinery that is synthesized by
      the diploid parent plant (sporophyte) and persists in mature pollen. As a result,
      the expected stringent selection against nonfunctional essential genes in the
      haploid state occurs in the female lineage but is relaxed in the male lineage.

PMID- 18723890
TI  - A "FLP-Out" system for controlled gene expression in Caenorhabditis elegans.
AB  - We present a two-part system for conditional FLP-out of FRT-flanked sequences in
      Caenorhabditis elegans to control gene activity in a spatially and/or temporally
      regulated manner. Using reporters, we assess the system for efficacy and
      demonstrate its use as a cell lineage marking tool. In addition, we construct and
      test a dominant-negative form of hlh-12, a gene that encodes a basic helix-loop
      helix (bHLH) transcription factor required for proper distal tip cell (DTC)
      migration. We show that this allele can be conditionally expressed from a heat
      inducible FLP recombinase and can interfere with DTC migration. Using the same
      DTC assay, we conditionally express an hlh-12 RNAi-hairpin and induce the DTC
      migration defect. Finally, we introduce a set of traditional and Gateway
      compatible vectors to facilitate construction of plasmids for this technology
      using any promoter, reporter, and gene/hairpin of interest.

PMID- 18723891
TI  - The evolution of sex-independent transmission ratio distortion involving multiple
      allelic interactions at a single locus in rice.
AB  - Transmission ratio distortion (TRD) is frequently observed in inter- and
      intraspecific hybrids of plants, leading to a violation of Mendelian inheritance.
      Sex-independent TRD (siTRD) was detected in a hybrid between Asian cultivated
      rice and its wild ancestor. Here we examined how siTRD caused by an allelic
      interaction at a specific locus arose in Asian rice species. The siTRD is
      controlled by the S6 locus via a mechanism in which the S6 allele acts as a
      gamete eliminator, and both the male and female gametes possessing the opposite
      allele (S6a) are aborted only in heterozygotes (S6/S6a). Fine mapping revealed
      that the S6 locus is located near the centromere of chromosome 6. Testcross
      experiments using near-isogenic lines (NILs) carrying either the S6 or S6a
      alleles revealed that Asian rice strains frequently harbor an additional allele
      (S6n) the presence of which, in heterozygotic states (S6/S6n and S6a/S6n), does
      not result in siTRD. A prominent reduction in the nucleotide diversity of S6 or
      S6a carriers relative to that of S6n carriers was detected in the chromosomal
      region. These results suggest that the two incompatible alleles (S6 and S6a)
      arose independently from S6n and established genetically discontinuous
      relationships between limited constituents of the Asian rice population.

PMID- 18723892
TI  - Selection mapping of loci for quantitative disease resistance in a diverse maize
      population.
AB  - The selection response of a complex maize population improved primarily for
      quantitative disease resistance to northern leaf blight (NLB) and secondarily for
      common rust resistance and agronomic phenotypes was investigated at the molecular
      genetic level. A tiered marker analysis with 151 simple sequence repeat (SSR)
      markers in 90 individuals of the population indicated that on average six alleles
      per locus were available for selection. An improved test statistic for selection
      mapping was developed, in which quantitative trait loci (QTL) are identified
      through the analysis of allele-frequency shifts at mapped multiallelic loci over
      generations of selection. After correcting for the multiple tests performed, 25
      SSR loci showed evidence of selection. Many of the putatively selected loci were
      unlinked and dispersed across the genome, which was consistent with the diffuse
      distribution of previously published QTL for NLB resistance. Compelling evidence
      for selection was found on maize chromosome 8, where several putatively selected
      loci colocalized with published NLB QTL and a race-specific resistance gene.
      Analysis of F2 populations derived from the selection mapping population
      suggested that multiple linked loci in this chromosomal segment were, in part,
      responsible for the selection response for quantitative resistance to NLB.

PMID- 18723893
TI  - A weighted-Holm procedure accounting for allele frequencies in genomewide
      association studies.
AB  - In the context of genomewide association studies where hundreds of thousand of
      polymorphisms are tested, stringent thresholds on the raw association test P
      values are generally used to limit false-positive results. Instead of using
      thresholds based on raw P-values as in Bonferroni and sequential Sidak (SidakSD)
      corrections, we propose here to use a weighted-Holm procedure with weights
      depending on allele frequency of the polymorphisms. This method is shown to
      substantially improve the power to detect associations, in particular by favoring
      the detection of rare variants with high genetic effects over more frequent ones
      with lower effects.

PMID- 18723894
TI  - Rtf1-mediated eukaryotic site-specific replication termination.
AB  - The molecular mechanisms mediating eukaryotic replication termination and pausing
      remain largely unknown. Here we present the molecular characterization of Rtf1
      that mediates site-specific replication termination at the polar
      Schizosaccharomyces pombe barrier RTS1. We show that Rtf1 possesses two chimeric
      myb/SANT domains: one is able to interact with the repeated motifs encoded by the
      RTS1 element as well as the elements enhancer region, while the other shows only
      a weak DNA binding activity. In addition we show that the C-terminal tail of Rtf1
      mediates self-interaction, and deletion of this tail has a dominant phenotype.
      Finally, we identify a point mutation in Rtf1 domain I that converts the RTS1
      element into a replication barrier of the opposite polarity. Together our data
      establish that multiple protein DNA and protein-protein interactions between Rtf1
      molecules and both the repeated motifs and the enhancer region of RTS1 are
      required for site-specific termination at the RTS1 element.

PMID- 18723895
TI  - The rate and character of spontaneous mutation in Thermus thermophilus.
AB  - Selection of spontaneous, loss-of-function mutations at two chromosomal loci
      (pyrF and pyrE) enabled the first molecular-level analysis of replication
      fidelity in the extremely thermophilic bacterium Thermus thermophilus. Two
      different methods yielded similar mutation rates, and mutational spectra
      determined by sequencing of independent mutants revealed a variety of replication
      errors distributed throughout the target genes. The genomic mutation rate
      estimated from these targets, 0.00097 +/- 0.00052 per replication, was lower than
      corresponding estimates from mesophilic microorganisms, primarily because of a
      low rate of base substitution. However, both the rate and spectrum of spontaneous
      mutations in T. thermophilus resembled those of the thermoacidophilic archaeon
      Sulfolobus acidocaldarius, despite important molecular differences between these
      two thermophiles and their genomes.

PMID- 18723896
TI  - Does exercise motivation predict engagement in objectively assessed bouts of
      moderate-intensity exercise? A self-determination theory perspective.
AB  - This study examined the utility of motivation as advanced by self-determination
      theory (Deci & Ryan, 2000) in predicting objectively assessed bouts of moderate
      intensity exercise behavior. Participants provided data pertaining to their
      exercise motivation. One week later, participants wore a combined accelerometer
      and heart rate monitor (Actiheart; Cambridge Neurotechnology Ltd) and 24-hr
      energy expenditure was estimated for 7 days. After controlling for gender and a
      combined marker of BMI and waist circumference, results showed autonomous
      motivation to positively predict moderate-intensity exercise bouts of >or=10 min,
      or=20 min, and an accumulation needed to meet public health recommendations for
      moderate intensity activity (i.e., ACSM/AHA guidelines). The present findings add
      bouts of objectively assessed exercise behavior to the growing body of literature
      that documents the adaptive consequences of engaging in exercise for autonomous
      reasons. Implications for practice and future work are discussed.

PMID- 18723897
TI  - Development and validation of the goal content for exercise questionnaire.
AB  - Self-determination theory (SDT; Deci & Ryan, 2000) proposes that intrinsic,
      relative to extrinsic, goal content is a critical predictor of the quality of an
      individual's behavior and psychological well-being. Through three studies, we
      developed and psychometrically tested a measure of intrinsic and extrinsic goal
      content in the exercise context: the Goal Content for Exercise Questionnaire
      (GCEQ). In adults, exploratory (N = 354; Study 1) and confirmatory factor
      analyses (N = 312; Study 2) supported a 20-item solution consisting of 5 lower
      order factors (i.e., social affiliation, health management, skill development,
      image and social recognition) that could be subsumed within a 2-factor higher
      order structure (i.e., intrinsic and extrinsic). Evidence for external validity,
      temporal stability, gender invariance, and internal consistency of the GCEQ was
      found. An independent sample (N = 475; Study 3) provided further support for the
      lower order structure of the GCEQ and some support for the higher order
      structure. The GCEQ was supported as a measure of exercise-based goal content,
      which may help understand how intrinsic and extrinsic goals can motivate exercise
      behavior.

PMID- 18723898
TI  - Using social cognitive theory to predict physical activity in inner-city African
      American school children.
AB  - Researchers using social cognitive theory and employing built environment
      constructs to predict physical activity (PA) in inner-city African American
      children is quite limited. Thus, the purpose of our investigation was to evaluate
      the ability of important social cognitive variables (e.g., self-efficacy) and
      built environment constructs (e.g., neighborhood hazards) to predict African
      American children's PA. Children (N = 331, ages 10-14) completed questionnaires
      assessing social cognitive theory constructs and PA. Using multiple regression
      analyses we were able to account for 19% of the variance in PA. Based on
      standardized beta weights, the best predictors of PA were time spent outside and
      social support derived from friends. These findings illuminate the valuable role
      of PA support from peers, as well as the simple act of going outside for inner
      city African American children.

PMID- 18723899
TI  - The anxiolytic effects of exercise: a meta-analysis of randomized trials and dose
      response analysis.
AB  - A meta-analysis was conducted to examine the effects of exercise on anxiety.
      Because previous meta-analyses in the area included studies of varying quality,
      only randomized, controlled trials were included in the present analysis. Results
      from 49 studies show an overall effect size of -0.48, indicating larger
      reductions in anxiety among exercise groups than no-treatment control groups.
      Exercise groups also showed greater reductions in anxiety compared with groups
      that received other forms of anxiety-reducing treatment (effect size = -0.19).
      Because only randomized, controlled trials were examined, these results provide
      Level 1, Grade A evidence for using exercise in the treatment of anxiety. In
      addition, exercise dose data were calculated to examine the relationship between
      dose of exercise and the corresponding magnitude of effect size.

PMID- 18723900
TI  - Levels of social complexity and dimensions of peer experiences in youth sport.
AB  - We assessed young adolescent female soccer players' perceptions of their peer
      group experiences. Data were collected via interviews with 34 girls from two
      youth soccer teams (M age = 13.0 years). Following inductive discovery analysis,
      data were subjected to an interpretive theoretical analysis guided by a model of
      peer experiences (Rubin, Bukowski, & Parker, 2006). Five categories of peer
      experiences were identified across three levels of social complexity. At the
      interaction level players integrated new members into the team and learned to
      interact with different types of people. At the relationship level players
      learned about managing peer conflict. At the group level a structure of
      leadership emerged and players learned to work together. Findings demonstrated
      interfaces between peer interactions, relationships, and group processes while
      also simplifying some apparently complex systems that characterized peer
      experiences on the teams studied.

PMID- 18723901
TI  - A social neuroscience perspective on physical activity.
AB  - The objective of this investigation was to examine the cognitive characteristics
      of individuals who demonstrate successful and unsuccessful self-regulation of
      physical activity behavior. In Study 1, participants articulated 1-week
      intentions for physical activity and wore a triaxial accelerometer over the
      subsequent 7 days. Among those who were motivated to increase their physical
      activity, those who were most and least successful were administered an IQ test.
      In Study 2, a second sample of participants completed the same protocol and a
      smaller subset of matched participants attended a functional imaging (fMRI)
      session. In Study 1, successful self-regulators (SSRs) scored significantly
      higher than unsuccessful self-regulators (USRs) on a test of general cognitive
      ability, and this difference could not be accounted for by favorability of
      attitudes toward physical activity or conscientiousness. In Study 2, the IQ
      effect was replicated, with SSRs showing a full standard deviation advantage over
      USRs. In the imaging protocol, USRs showed heavier recruitment of cognitive
      resources relative to SSRs in the anterior cingulate and orbitofrontal cortex
      during performance of a Stroop task; SSRs showed heavier recruitment in the right
      dorsolateral prefrontal cortex.

PMID- 18723902
TI  - Avoidance motivation and choking under pressure in soccer penalty shootouts.
AB  - The purpose of this study was to examine the relationships between shot valence,
      avoidance behavior, and performance in soccer penalty shootouts. Video analyses
      were conducted with all penalty shootouts ever held in the World Cup, the
      European Championships, and the UEFA Champions League (n = 36 shootouts, 359
      kicks). Shot valence was assessed from the potential consequences of a shot
      outcome as follows: Shots where a goal instantly leads to victory were classified
      as positive valence shots and shots where a miss instantly leads to loss as
      negative valence shots. Avoidance behavior was defined as looking away from the
      goalkeeper or preparing the shot quickly (thus speeding up the wait). The results
      showed that avoidance behavior occurred more with negative valence shots than
      with positive shots and that players with negative valence shots performed worse
      than those with positive shots. Thus, avoidance motivation may help explain why
      professional athletes occasionally choke under pressure.

PMID- 18723903
TI  - Routine immunization, India's Achilles heel.

PMID- 18723904
TI  - TV coverage of tragedies: what is the impact on children?

PMID- 18723905
TI  - Consensus recommendations on immunization, 2008.
AB  - JUSTIFICATION: There is a need to formulate recommendations regarding use of new
      vaccines which have become recently available/will soon be available and to
      review/revise recommendations about existing vaccines in light of recent
      information. PROCESS: Following an IAPCOI meeting in March 2008, a draft
      statement was prepared and circulated among the meeting participants to arrive at
      a consensus. OBJECTIVES: To formulate recommendations pertaining to use of Tdap,
      human papilloma virus (HPV) vaccines and rotavirus vaccines and to revise
      recommendations pertaining to use of pneumococcal and inactivated poliovirus
      vaccines (IPV). These recommendations are primarily for pediatricians in office
      practice. RECOMMENDATIONS: IAP COI recommends (i) offering Tdap vaccine instead
      of Td/TT vaccine to all children/ adolescents who can afford to use the vaccine
      at the age of 10-12 yrs; (ii) offering HPV vaccine to all females who can afford
      the vaccine at the age of 10-12 years; (iii) offering both seven valent
      pneumococcal conjugate vaccine (PCV 7) and 23 valent pneumococcal polysaccharide
      vaccine (PPV 23) in all high risk children who can afford the vaccine; (iv)
      offering IPV in addition to oral poliovirus vaccine (OPV) in all children who can
      afford the vaccine at the age of 6, 10, 14 weeks and a booster at 15-18 months;
      (v) the use of oral rotavirus vaccines after one-to-one discussion with parents
      beginning age 6 weeks; and (iv) the use of PCV 7 in healthy children aged below 2
      years after one-to-one discussion with parents at the age of 6, 10, 14 weeks and
      booster at 15-18 months.

PMID- 18723906
TI  - Intravenous immunoglobulin in neonatal rhesus hemolytic disease.

PMID- 18723907
TI  - Single versus multiple courses of antenatal corticosteroids.

PMID- 18723908
TI  - Efficacy of two dose regimes of intravenous immunoglobulin in Rh hemolytic
      disease of newborn--a randomized controlled trial.
AB  - OBJECTIVE: To compare the effect of two dose regimes of IVIg (0.5 g/kg vs. 1g/kg
      given soon after birth) on duration of phototherapy in Rh-isoimmunized neonates
      32 week and above gestation. DESIGN: Randomized controlled trial. SETTING:
      Tertiary care hospital. SUBJECTS: Rh positive blood group neonates of gestation
      32 weeks and above born to Rh negative mothers having positive Direct Coombs test
      and without any major malformation. INTERVENTION: Intravenous immunoglobulin
      (IVIg) infusion over 2 h either 0.5 g/kg (low dose group, n=19) or 1.0 g/kg (high
      dose group, n=19). PRIMARY OUTCOME VARIABLE: Duration of phototherapy. RESULTS:
      The mean duration of phototherapy was 77.3+/-57.2 h in low dose group versus
      55.4+/-49 h in high dose group (mean difference=21.9; 95% CI-13.1 to 56.9). There
      was no difference in need for exchange transfusion (21% in both the groups) and
      requirement of packed red blood cells transfusion (12 transfusions in both
      groups). The duration of hospital stay was similar [8.4+/-6.9 and 13.6+/-14.8
      days, respectively (mean difference=-5.1; 95% CI-12.8 to 2.5)]. No adverse
      effects of IVIg administration were noted. CONCLUSION: Two regimens of IVIg (0.5
      g/Kg or 1 g/Kg) had comparable effect on duration of phototherapy, duration of
      hospital stay and exchange transfusion requirement, in Rh isoimmunized neonates
      of gestation 32 weeks and above.

PMID- 18723909
TI  - Single versus multiple courses of antenatal betamethasone and neonatal outcome: a
      randomized controlled trial.
AB  - OBJECTIVES: This study compared the beneficial and adverse neonatal effects of a
      single versus repeated courses of antenatal betamethasone. SETTING: Tertiary care
      hospital DESIGN: Open labeled, randomized controlled trial. PARTICIPANTS:
      Pregnant women (26-33 weeks) at risk of preterm delivery, who received one course
      of antenatal betamethasone and remained undelivered for 7 days. Those with
      uncertain gestation, major malformations and frank chorioamnionitis were
      excluded. INTERVENTIONS: Subjects were randomized to receive weekly antenatal
      betamethasone until 34 weeks or no further betamethasone. OUTCOME MEASURES:
      Primary: incidence of severe respiratory distress syndrome (RDS). Secondary:
      incidence of non-severe RDS and other neonatal morbidity; birth weight, length
      and occipito-frontal circumference (OFC); and, development and growth at 6 mo
      corrected age. RESULTS: 38 subjects were allocated to each group. Severe RDS was
      similar in multiple and single course groups (7% vs. 3% respectively, P=0.34), as
      was incidence of other morbidity. Composite outcome of RDS and or death within 28
      days tended to be less in multiple course group (P=0.07). Birth anthropometry was
      similar in the 2 groups. At 6 mo corrected age (n=44), weight and length were
      significantly lower in multiple course group (p=0.003 and P=0.007, respectively),
      whereas OFC was not different (P=0.1). There were no differences vis a vis
      neurodevelopmental outcomes. CONCLUSIONS: A single course of antenatal
      betamethasone was as efficacious as multiple courses, with respect to prevention
      of neonatal morbidity. Multiple antenatal betamethasone courses have long-term
      adverse effects on infant weight and length growth, but not on OFC and
      neurodevelopment.

PMID- 18723910
TI  - Thrombocytosis in childhood.
AB  - Thrombocytosis is a frequent finding in hemograms obtained from hospitalized and
      ambulatory children due to the widespread use of automated blood cell counters.
      Pediatricians are commonly puzzled in cases of thrombocytosis to determine the
      underlying cause and the need for therapy. The purpose of this review is to
      assist the general pediatrician into dealing with this common hematological
      finding in every day clinical practice. Fortunately, primary thrombocytosis or
      essential thrombocythemia, a clonal disease, is exceedingly rare in childhood,
      but may be associated with thromboembolic and hemorrhagic complications. On the
      other hand, secondary or reactive thrombocytosis is very common and is due to a
      variety of conditions, such as acute and chronic infections, iron deficiency,
      bleeding, hemolytic anemias, collagen vascular diseases, malignancies, drugs and
      splenectomy. Treatment of reactive thrombocytosis should be directed to the
      underlying problem alone. Administration of platelet aggregation inhibitors such
      as aspirin is unwarranted. Consultation is necessary only for the rare child with
      extreme thrombocytosis who has clinical and/or laboratory criteria consistent
      with essential thrombocythemia, or in whom a hemorrhagic or thrombotic
      complication has developed.

PMID- 18723911
TI  - Child soldiers global report 2008: a timely reminder.

PMID- 18723912
TI  - Anti malarial drugs for prevention of malaria.

PMID- 18723913
TI  - Langerhans' cell histiocytosis: experience from a single center.
AB  - Clinical profile, disease-distribution and outcome of Langerhans cell
      histiocytosis (LCH) is presented in this retrospective analysis. There were 69
      children with LCH from January 1986 to December 2004. Diagnosis was presumptive
      in the majority. The age ranged from 2 months to 12 years. Multisystem disease
      was documented in 48 (69.6%) children. Evidence of hepatic dysfunction was
      detected in 25 (36.2%). An elevated serum alkaline phosphatase was a prominent
      observation in patients with hepatic involvement. Children with localized disease
      received oral steroids, while cases with disseminated/multi-system disease were
      treated with prednisolone and, vinblastine or etoposide. 20 (54%) children with
      disseminated disease and organ dysfunction died. A favorable outcome was
      documented in all but one case with localized disease. Portal hypertension
      developed in 3 cases, all of whom had a fatal outcome. Twelve (17.4%) patients
      had diabetes insipidus. Disseminated disease with organ dysfunction was observed
      to be a predictor of fatal outcome.

PMID- 18723914
TI  - Recurrent urinary tract infection and functional voiding disorders.
AB  - This study was carried out to determine the association of recurrent urinary
      tract infections with functional voiding disorders. Sixty eight children with
      suspected functional voiding disorders were prospectively evaluated clinically
      and by non-invasive urodynamics. Invasive urodynamics were carried out when
      indicated. Group I comprised 34 children with symptoms suggestive of functional
      voiding disorders and recurrent urinary tract infections (mean age 6.3+/-2 yr)
      and Group II comprised 34 children with symptoms suggestive of functional voiding
      disorders without recurrent urinary tract infections (mean age 6.7+/-2 yr). The
      underlying bladder abnormalities in Groups I and II were detrusor instability in
      22 (64.7%) and 30 (88.2%), respectively (P>0.05) and dysynergic voiding in 10
      (29.4%), and 1 (2.9%), respectively (P<0.05). Children with recurrent urinary
      tract infections are more likely to have a dysynergic voiding pattern than
      children presenting with other symptoms of functional voiding disorders.

PMID- 18723915
TI  - Klebsiella pneumoniae brain abscess in two neonates.
AB  - We report two premature infants who developed multiple brain abscesses following
      Klebsiella pneumoniae infection. Both the cases were diagnosed by ultrasonogram
      (USG) and cranial tomography. Abscess had intraventricular communication in one
      case. One infant was managed conservatively while the other required surgical
      drainage.

PMID- 18723916
TI  - Congenital hypoaldosteronism.
AB  - Congenital hypoaldosteronism due to an isolated aldosterone biosynthesis defect
      is rare. We report a 4 month old female infant who presented with failure to
      thrive, persistent hyponatremia and hyperkalemia. Investigations revealed normal
      serum 17 hydroxy progesterone and cortisol. A decreased serum aldosterone and
      serum 18 hydroxy corticosterone levels with a low 18 hydroxy corticosterone:
      aldosterone ratio was suggestive of corticosterone methyl oxidase type I
      deficiency. She was started on fludrocortisone replacement therapy with a
      subsequent normalization of electrolytes. Further molecular analysis is needed to
      ascertain the precise nature of the mutation.

PMID- 18723917
TI  - Scarabiasis.
AB  - Scarabiasis is a condition where beetles temporarily infest the digestive tract
      and the scarabes are identified in the fly away from the anus at the time of the
      defecation. This article highlights this rare problem of scarabiasis in a 4 year
      old girl that responded to bowel cleansing and personal hygienic measures.

PMID- 18723918
TI  - Situs inversus with autosomal recessive polycystic kidney disease.

PMID- 18723919
TI  - Prescribing pattern of zinc and antimicrobials in acute diarrhea.

PMID- 18723920
TI  - Transient atrioventricular dissociation in Kawasaki disease.

PMID- 18723921
TI  - Klebsiella septicemia presenting as renal subcapsular abscess and hypertension in
      a neonate.

PMID- 18723924
TI  - Crystal identification in positron emission tomography using nonrigid
      registration to a Fourier-based template.
AB  - Modern positron emission tomography (PET) detectors are typically made from 2D
      modular arrays of scintillation crystals. Their characteristic flood field
      response (or flood histogram) must be segmented in order to correctly determine
      the crystal of annihilation photon interaction in the system. Crystal
      identification information thus generated is also needed for accurate system
      modeling as well as for detailed detector characterization and performance
      studies. In this paper, we present a semi-automatic general purpose template
      guided scheme for the segmentation of flood histograms. We first generate a
      template image that exploits the spatial frequency information in the given flood
      histogram using Fourier-space analysis. This template image is a lower order
      approximation of the flood histogram, and can be segmented with horizontal and
      vertical lines drawn midway between adjacent peaks in the histogram. The template
      is then registered to the given flood histogram by a diffeomorphic polynomial
      based warping scheme that is capable of iteratively minimizing intensity
      differences. The displacement field thus calculated is applied to the
      segmentation of the template resulting in a segmentation of the given flood
      histogram. We evaluate our segmentation scheme for a photomultiplier tube based
      PET detector, a detector with readout by a position-sensitive avalanche
      photodiode (PSAPD) and a detector consisting of a stack of photomultiplier tubes
      and scintillator arrays. Further, we quantitatively compare the performance of
      the proposed method to that of a manual segmentation scheme using reconstructed
      images of a line-source phantom. We also present an adaptive method for
      distortion reduction in flood histograms obtained for PET detectors that use
      PSAPDs.

PMID- 18723925
TI  - Image registration of a moving target phantom with helical tomotherapy: effect of
      the CT acquisition technique and action level proposal.
AB  - This study aims to quantify the effects of target motion and resultant motion
      artifacts in planning and megavoltage CT (MVCT) studies on the automatic
      registration processes of helical tomotherapy. Clinical and experimental data
      were used to derive an action level for patient repositioning on helical
      tomotherapy. Planning CT studies of a respiratory motion phantom were acquired
      using conventional and four-dimensional CT (4D CT) techniques. MVCT studies were
      acquired on helical tomotherapy in the presence and absence of target motion and
      were registered with different planning CT studies. The residual errors of the
      registration process were calculated from the registration values to quantify the
      ability of the process to detect 5 or 10 mm translations of the phantom in two
      directions. Twenty-seven registration combinations of MVCT inter-slice spacing,
      technique and resolution were investigated. The residual errors were used as an
      estimate of the localization error of the registration process, and the accuracy
      of couch repositioning was determined from couch position measurements during 866
      treatment fractions. These two parameters were used to calculate the action level
      for patient repositioning on helical tomotherapy. Automatic registration of an
      MVCT study with 0% breathing phase, average intensity and maximum intensity 4D CT
      projections did not differ from that of an MVCT study with a conventional
      planning CT. Motion artifacts in the MVCT or planning CT studies changed the
      accuracy of the automatic registration process by less than 2.0%. The action
      level for patient repositioning using MVCT studies of 6 mm inter-slice spacing
      was determined to be 0.7, 1.1 and 0.6 mm in the x-, y- and z-directions,
      respectively. These action levels have the greatest effect on treatments for
      disease sites in the brain.

PMID- 18723926
TI  - A mathematical approach for evaluating the influence of dose heterogeneity on TCP
      for prostate cancer brachytherapy treatment.
AB  - The low-dose-rate brachytherapy technique has proven suitable for the management
      of prostate cancer. However, published data generally report the clinical outcome
      and the minimum peripheral dose (mPD) to the target volume and not the actual
      dose distribution in patients. To this end, modern guidelines recommend the use
      of specific dose and volume indices describing dose distribution throughout the
      target. The introduction of a method, based on the standard linear quadratic
      model and Poisson statistics, entitled the F-factor allows the TCP from different
      DVHs to be calculated, by using the TCP from a uniform dose distribution as the
      reference. The F-factor sensitivity against radiobiological parameters and
      influence of the DVH were evaluated. We applied the F-formula on the post-plan
      DVHs of 58 patients treated with (125)I permanent seed implant brachytherapy for
      localized prostate cancer. F shows a strong correlation with dosimetric
      parameters already reported as significant predictors of the biochemical outcome.

PMID- 18723927
TI  - Linac mechanic QA using a cylindrical phantom.
AB  - Precise mechanical operation of a linear accelerator (linac) is critical for
      accurate radiation therapy dose delivery. Quantitative procedures for linac
      mechanical quality assurance (QA) used in the standard of care are time consuming
      and therefore conducted on a relatively infrequent basis. We present a method for
      evaluating the mechanical performance of a linac based on a series of projection
      portal images of a prototype cylindrical phantom with embedded radiopaque
      fiducial markers. The marker autodetection process included modeling imager
      response to the radiation beam where the projected cylinder attenuation yielded a
      non-uniform image background. The linac mechanical characteristics were estimated
      based on nonlinear multi-objective optimization of the projected marker
      locations. The estimated geometry parameters for the tested commercial model were
      gantry angle deviation 0.075 +/- 0.076 degrees (1 SD), gantry sag 0.026 +/- 0.02
      degrees , source-to-axis distance SAD 998.3 +/- 1.7 mm, source-to-detector
      distance SDD 1493 +/- 5.0 mm, couch vertical motion 0.6 +/- 0.45 mm, couch
      rotation 0.154 +/- 0.1 degrees and average linac rotation center (1.02, -0.27, 
      0.37) +/- (0.36,0.333,1.20) mm relative to the laser intersection. The imager
      shift was [-0.44, 2.6] +/- [0.20, 1.1] mm and the imager orientation was in-plane
      rotation 0.05 +/- 0.03 degrees , roll -0.14 +/- 0.09 degrees and pitch -0.9 +/-
      0.604 degrees . The performance of this procedure concerning marker detection and
      optimization was examined by comparing the detected set of marker coordinates to
      its back-calculated counterpart for three subgroups of markers: central, wall and
      intermediate relative to the center of the phantom. The maximum difference was
      less than 0.25 mm with a mean of 0.146 mm and a standard deviation of 0.07 mm.
      The clinical use of this automated procedure will allow more efficient, more
      thorough, and more frequent mechanical linac QA.

PMID- 18723928
TI  - Phase gradient mapping as an aid in the analysis of object-induced and system
      related phase perturbations in MRI.
AB  - In this note we wish to demonstrate the utility of phase gradient mapping (PGM)
      as an aid in the analysis and characterization of object-induced and system
      related macroscopic phase perturbations in MRI. To achieve this goal, phase
      gradient maps and, if applicable, field gradient maps were derived from standard
      phase images via a forward difference operator taking into account phase wraps.
      By way of phantom experiments, PGM was shown to provide reliable phase and field
      gradient information, even in regions with multiple phase wraps. Phase gradient
      mapping was further shown to allow positive identification of local phase and
      field perturbations and global discrimination between positive and negative local
      susceptibility deviations. The suitability of PGM for in vivo studies was
      demonstrated by a 3D brain examination of a healthy volunteer.

PMID- 18723929
TI  - Effect of transverse magnetic fields on dose distribution and RBE of photon
      beams: comparing PENELOPE and EGS4 Monte Carlo codes.
AB  - The application of a strong transverse magnetic field to a volume undergoing
      irradiation by a photon beam can produce localized regions of dose enhancement
      and dose reduction. This study uses the PENELOPE Monte Carlo code to investigate
      the effect of a slice of uniform transverse magnetic field on a photon beam using
      different magnetic field strengths and photon beam energies. The maximum and
      minimum dose yields obtained in the regions of dose enhancement and dose
      reduction are compared to those obtained with the EGS4 Monte Carlo code in a
      study by Li et al (2001), who investigated the effect of a slice of uniform
      transverse magnetic field (1 to 20 Tesla) applied to high-energy photon beams.
      PENELOPE simulations yielded maximum dose enhancements and dose reductions as
      much as 111% and 77%, respectively, where most results were within 6% of the EGS4
      result. Further PENELOPE simulations were performed with the Sheikh-Bagheri and
      Rogers (2002) input spectra for 6, 10 and 15 MV photon beams, yielding results
      within 4% of those obtained with the Mohan et al (1985) spectra. Small
      discrepancies between a few of the EGS4 and PENELOPE results prompted an
      investigation into the influence of the PENELOPE elastic scattering parameters
      C(1) and C(2) and low-energy electron and photon transport cut-offs. Repeating
      the simulations with smaller scoring bins improved the resolution of the regions
      of dose enhancement and dose reduction, especially near the magnetic field
      boundaries where the dose deposition can abruptly increase or decrease. This
      study also investigates the effect of a magnetic field on the low-energy electron
      spectrum that may correspond to a change in the radiobiological effectiveness
      (RBE). Simulations show that the increase in dose is achieved predominantly
      through the lower energy electron population.

PMID- 18723930
TI  - Ionization chamber volume determination and quality assurance using micro-CT
      imaging.
AB  - Ion chamber dosimetry requires a high degree of precision, at all steps within
      the dosimetric process, in order to ensure accurate dose measurements. This work
      presents a novel technique for ion chamber volume determination and quality
      assurance, using micro-computed tomography (micro-CT). Four nominally identical
      Exradin A1SL chambers (0.056 cm(3)) (Standard Imaging, WI, USA) were imaged using
      a micro-CT system (GE Locus, GE Healthcare, London, Ontario) and irradiated in a
      6 MV x-ray reference field. Air volumes were calculated from the CT datasets
      using 3D analysis software (Microview 2.1.1, General Electric Healthcare, London,
      Ontario). Differences in the volumes of each chamber determined using micro-CT
      images agreed with differences in the ionization response within 1% for each
      chamber. Calibration coefficients were then compared through cross-calibration
      with a calibrated ion chamber and from the CT-measured volumes. The average ratio
      of these values was found to be 0.958 +/- 0.009 indicating good correlation. The
      results demonstrate the promise of using micro-CT imaging for the absolute
      volumetric characterization of ion chambers. The images have the potential to be
      an important clinical tool for quality assurance of ion chamber construction and
      integrity after routine clinical usage.

PMID- 18723931
TI  - DQE analysis on a dual detector phase x-ray imaging system.
AB  - This study presents the characterization results of a newly developed dual
      detector in-line phase x-ray imaging prototype. Comparison of modulation transfer
      function (MTF), noise power spectrum (NPS) and detective quantum efficiency (DQE)
      for both detectors was conducted when they worked in the dual detection mode, in
      which two images are acquired simultaneously at a single exposure. The MTFs of
      the two detectors are almost identical, showing that the blurring caused by
      detector1 does not significantly weaken the resolving power of detector2. With a
      40 kVp and 4 cm thick BR-12 phantom filtered x-ray beam, the transmittance of
      detector1 was measured to be 32%. The characteristic response and DQE of the two
      detectors almost coincide, showing that the two detectors have similar imaging
      performance under the imaging conditions of this study. The DQE of detector2 at
      the different source to detector distances (SID) also demonstrate a high level of
      agreement, implying that the reduced exposure level caused by elongated SID did
      not degrade the performance significantly. The study validated the design of the
      dual detection configuration for phase x-ray imaging, which has the potential for
      improving the accuracy of diagnostics at clinically acceptable radiation doses.

PMID- 18723933
TI  - Fisher information and Shannon entropy for on-line detection of transient signal
      high-values in laser Doppler flowmetry signals of healthy subjects.
AB  - Laser Doppler flowmetry (LDF) is an easy-to-use method for the assessment of
      microcirculatory blood flow in tissues. However, LDF recordings very often
      present TRAnsient Signal High-values (TRASH), generally of a few seconds. These
      TRASH can come from tissue motions, optical fibre movements, movements of the
      probe head relative to the tissue, etc. They often lead to difficulties in signal
      global interpretations. In order to test the possibility of detecting
      automatically these TRASH for their removal, we process noisy and noiseless LDF
      signals with two indices from information theory, namely Fisher information and
      Shannon entropy. For this purpose, LDF signals from 13 healthy subjects are
      recorded at rest, during vascular occlusion of 3 min, and during post-occlusive
      hyperaemia. Computation of Fisher information and Shannon entropy values shows
      that, when calibrated, these two indices can be complementary to detect TRASH and
      be insensitive to the rapid increases of blood flow induced by post-occlusive
      hyperaemia. Moreover, the real-time algorithm has the advantage of being easy to
      implement and does not require any frequency analysis. This study opens new
      fields of application for Fisher information and Shannon entropy: LDF
      'denoising'.

PMID- 18723932
TI  - A practical exposure-equivalent metric for instrumentation noise in x-ray imaging
      systems.
AB  - The performance of high-sensitivity x-ray imagers may be limited by additive
      instrumentation noise rather than by quantum noise when operated at the low
      exposure rates used in fluoroscopic procedures. The equipment-invasive
      instrumentation noise measures (in terms of electrons) are generally difficult to
      make and are potentially not as helpful in clinical practice as would be a direct
      radiological representation of such noise that may be determined in the field. In
      this work, we define a clinically relevant representation for instrumentation
      noise in terms of noise-equivalent detector entrance exposure, termed the
      instrumentation noise-equivalent exposure (INEE), which can be determined through
      experimental measurements of noise-variance or signal-to-noise ratio (SNR). The
      INEE was measured for various detectors, thus demonstrating its usefulness in
      terms of providing information about the effective operating range of the various
      detectors. A simulation study is presented to demonstrate the robustness of this
      metric against post-processing, and its dependence on inherent detector blur.
      These studies suggest that the INEE may be a practical gauge to determine and
      compare the range of quantum-limited performance for clinical x-ray detectors of
      different design, with the implication that detector performance at exposures
      below the INEE will be instrumentation-noise limited rather than quantum-noise
      limited.

PMID- 18723934
TI  - Two hybrid regularization frameworks for solving the electrocardiography inverse
      problem.
AB  - In this paper, two hybrid regularization frameworks, LSQR-Tik and Tik-LSQR, which
      integrate the properties of the direct regularization method (Tikhonov) and the
      iterative regularization method (LSQR), have been proposed and investigated for
      solving ECG inverse problems. The LSQR-Tik method is based on the Lanczos
      process, which yields a sequence of small bidiagonal systems to approximate the
      original ill-posed problem and then the Tikhonov regularization method is applied
      to stabilize the projected problem. The Tik-LSQR method is formulated as an
      iterative LSQR inverse, augmented with a Tikhonov-like prior information term.
      The performances of these two hybrid methods are evaluated using a realistic
      heart-torso model simulation protocol, in which the heart surface source method
      is employed to calculate the simulated epicardial potentials (EPs) from the
      action potentials (APs), and then the acquired EPs are used to calculate
      simulated body surface potentials (BSPs). The results show that the regularized
      solutions obtained by the LSQR-Tik method are approximate to those of the
      Tikhonov method, the computational cost of the LSQR-Tik method, however, is much
      less than that of the Tikhonov method. Moreover, the Tik-LSQR scheme can
      reconstruct the epcicardial potential distribution more accurately, specifically
      for the BSPs with large noisy cases. This investigation suggests that hybrid
      regularization methods may be more effective than separate regularization
      approaches for ECG inverse problems.

PMID- 18723935
TI  - Changes in wall motion and blood flow in the outflow tract of chick embryonic
      hearts observed with optical coherence tomography after outflow tract banding and
      vitelline-vein ligation.
AB  - Optical coherence tomography (OCT) is a non-contact, non-invasive and high
      resolution imaging technique, suited to study early cardiovascular development.
      Alterations in hemodynamic conditions during early development are known to lead
      to cardiac defects, presumably as a result of changes in cardiac biomechanics
      produced by the alterations. In this paper, we demonstrate the use of a spectral
      domain OCT in visualizing and quantifying changes in cardiac wall motion and
      blood-flow velocities under normal and altered hemodynamic conditions in chicken
      embryos at an early stage of development (Hamburger-Hamilton stage HH18,
      approximately 3 days of incubation), focusing on the heart outflow tract (OFT).
      The OCT system employed acquired simultaneously microstructural and blood-flow
      images at a rate of 92 frames s(-1)with a spatial resolution of approximately 10
      microm. OCT imaging allowed in vivo visualization of the OFT microstructures,
      e.g. the lumen, cardiac cushions and myocardium. We found that alterations in
      hemodynamic conditions, through OFT banding and vitelline-vein ligation, changed
      blood-flow velocities through the OFT, as expected. Further, OCT allowed
      quantification of changes in the dynamics of OFT wall motion. Our results
      therefore establish the utility of spectral domain OCT to study the influence of
      hemodynamic conditions on heart development in intact, in vivo chicken embryo
      models.

PMID- 18723937
TI  - Introduction. Philosophy of medicine.

PMID- 18723938
TI  - Risk and disease.
AB  - The way that diseases such as high blood pressure (hypertension), high
      cholesterol, and diabetes are defined is closely tied to ideas about modifiable
      risk. In particular, the threshold for diagnosing each of these conditions is set
      at the level where future risk of disease can be reduced by lowering the relevant
      parameter (of blood pressure, low-density lipoprotein, or blood glucose,
      respectively). In this article, I make the case that these criteria, and those
      for diagnosing and treating other "risk-based diseases," reflect an unfortunate
      trend towards reclassifying risk as disease. I closely examine stage 1
      hypertension and high cholesterol and argue that many patients diagnosed with
      these "diseases" do not actually have a pathological condition. In addition,
      though, I argue that the fact that they are risk factors, rather than diseases,
      does not diminish the importance of treating them, since there is good evidence
      that such treatment can reduce morbidity and mortality. For both philosophical
      and ethical reasons, however, the conditions should not be labeled as
      pathological. The tendency to reclassify risk factors as diseases is an important
      trend to examine and critique.

PMID- 18723939
TI  - Mental illness from the perspective of theoretical neuroscience.
AB  - Theoretical neuroscience, which characterizes neural mechanisms using
      mathematical and computational models, is highly relevant to central problems in
      the philosophy of psychiatry. These models can help to solve the explanation
      problem of causally connecting neural processes with the behaviors and
      experiences found in mental illnesses. Such explanations will also be useful for
      generating better classifications and treatments of psychiatric disorders. The
      result should help to eliminate concerns that mental illnesses such as depression
      and schizophrenia are not objectively real. A philosophical approach to mental
      illness based on neuroscience need not neglect the inherently social and
      historical nature of mental phenomena.

PMID- 18723940
TI  - Constructive realism and medicine: an approach to medical ontology.
AB  - Metaphysics is an essential part of philosophy of medicine, providing the
      background for further methodological work. Current accounts of the ontology of
      particular diseases may be classified as realist or anti-realist. Because strong
      arguments can be marshaled by both of these positions, an approach to medical
      ontology that draws support from both sides of this divide would be desirable.
      Abstract models, as described by Ronald Giere, provide such an approach. After a
      review of Giere's account of mechanics, I show how abstract models can provide an
      account of the ontology of diseases.

PMID- 18723941
TI  - Do we need theory to study disease? Lessons from cancer research and their
      implications for mental illness.
AB  - This article applies general ideas from contemporary philosophy of science--chief
      among them that much good science proceeds without theories and laws--to the
      science of medicine. I claim that traditional philosophical debates over the
      nature of disease make demands on medicine that are mistaken. I demonstrate this
      philosophical error by applying the perspective of the philosophy of science to
      understanding the nature of disease in two concrete cases, cancer and depression.
      I first argue that cancer research produces various kinds of piecemeal causal
      explanation and does so without any well-developed theory of normal and malignant
      functioning, despite the rhetoric of some leading cancer researchers. I then
      defuse doubts about the scientific status of psychiatry, by demonstrating that it
      is not necessary to have a theory of normal functioning in order to understand
      and treat depression.

PMID- 18723942
TI  - Philosophy of medicine is what philosophers of medicine do.
AB  - Philosophy of medicine cannot be precisely defined because neither philosophy nor
      medicine can be precisely defined. Furthermore, philosophers of medicine do not
      constitute a well-defined class because they come not only from the fields of
      philosophy and medicine, but also from various other disciplines. Hence, I argue
      for a broad conception of philosophy of medicine that includes philosophical
      reflection on any matter considered to belong to medicine. A brief survey of the
      philosophy of medicine literature supports this view. Of the 625 articles
      surveyed for the years 1997-2006, nearly three-quarters dealt with matters of
      ethics, and of the 36 books surveyed, nearly 60% were primarily on ethics.
      Nonetheless, articles and books focusing on all other major branches of
      philosophy--metaphysics, epistemology, aesthetics, and logic--were also
      published. Moreover, many of the articles, even those primarily on ethics, dealt
      in significant ways with more than one branch of philosophy. I conclude that
      philosophy of medicine includes all sorts of philosophical reflection on medicine
      but is currently dominated by ethics. Given the stated purpose of journals and
      book series devoted to philosophy and medicine, this leaves ample room to expand
      other philosophical reflection on medicine.

PMID- 18723943
TI  - Reflections on humanizing biomedicine.
AB  - Although biomedicine is responsible for the "miracles" of modern medicine,
      paradoxically it has also led to a quality-of-care crisis in which many patients
      feel disenfranchised from the health-care industry. To address this crisis,
      several medical commentators make an appeal for humanizing biomedicine, which has
      led to shifts in the philosophical boundaries of medical knowledge and practice.
      In this paper, the metaphysical, epistemological, and ethical boundaries of
      biomedicine and its humanized versions are investigated and compared to one
      another. Biomedicine is founded on a metaphysical position of mechanistic monism,
      an epistemology of objective knowing, and an ethic of emotionally detached
      concern. In humanizing modern medicine, these boundaries are often shifted to a
      metaphysical position of dualism/holism, an epistemology of subject knowing, and
      an ethic of empathic care. In a concluding section, the question is discussed
      whether these shifts in the philosophical boundaries are adequate to resolve the
      quality-of-care crisis.

PMID- 18723944
TI  - Epistemological reflections on the art of medicine and narrative medicine.
AB  - This article challenges the widespread view that there is both a science and an
      art of medicine. Through examination of recent work in medical humanities --Jodi
      Halpern's From Detached Concern to Empathy (2001), Kathryn Montgomery's How
      Doctors Think (2006), and Rita Charon's Narrative Medicine (2006)--I argue that
      while a variety of epistemic techniques are important in medicine, it is not
      helpful to dichotomize them as "science" versus "art." I assess the epistemic
      strengths and weaknesses of narrative medicine, a recent exemplar of humanistic
      medicine.

PMID- 18723945
TI  - Evidence and ethics in medicine.
AB  - Ethics and epistemology in medicine are more closely and more interestingly
      intertwined than is usually recognized. To explore this relationship, I present a
      case study, clinical trials of extracorporeal membrane oxygenation (ECMO; an
      intervention for persistent pulmonary hypertension of the newborn).Three separate
      ethical issues that arise from this case study-whether or not it is ethical to
      perform a certain trial at all, whether stopping rules for trials are ethically
      mandated, and the issue of informed consent-are all shown to be intimately
      related to epistemological judgments about the weight of evidence. Although
      ethical issues cannot, of course, be resolved by consideration of epistemological
      findings, I argue that no informed view of the ethical issues that are raised can
      be adopted without first taking an informed view of the evidential
      epistemological ones.

PMID- 18723946
TI  - Health as intra-systemic integrity: rethinking the foundations of systems biology
      and nanomedicine.
AB  - In current research on systems biology and nanomedicine, we often find an ideal
      of a new science-based preventive medicine. I consider how disease, cause,
      explanation, diagnosis, and treatment are understood within this ideal, with
      special attention to the role of nanoscience and technology in elucidating the
      "circuit diagram" of a healthy system. I argue that the developmental systems
      theory that informed George Engel's biopsychosocial model addresses some
      deficiencies in the current systems ideal, but it needs to be integrated with an
      ethical analysis that is more attentive to the socioeconomic, cultural, and
      institutional factors that condition how we understand and manage disease. We
      also need a richer account of top-down causal paths if we are to appropriately
      understand diseases as disruptions of inter- and intra-systemic integrity.

PMID- 18723947
TI  - Medicine and the call for a moral epistemology, part II: constructing a synthesis
      of values.
AB  - The demands and needs of an individual patient require diverse value judgments to
      interpret and apply clinical data. Indeed, objective assessment takes on
      particular meaning in the context of the social and existential status of the
      patient, and thereby a complex calculus of values determines therapeutic goals. I
      have previously formulated how this moral thread of care becomes woven into the
      epistemological project as a "moral epistemology." Having argued its ethical
      justification elsewhere, I offer another perspective here: clinical choices
      employ diverse values directed at an array of goals, some of which are derived
      from a universal clinical science and others from the particular physiological,
      psychological, and social needs of the patient. Integrating these diverse
      elements that determine clinical care requires a complex synthesis of facts and
      judgments from several domains. This constructivist process relies on clinical
      facts, as well as on personal judgments and subjective assessments in an ongoing
      negotiation between patient and doctor. A philosophy of medicine must account for
      the conceptual basis of this process by identifying and addressing the judgments
      that govern the complex synthesis of these various elements.

PMID- 18723948
TI  - The changing face of "real research".
AB  - Over the past 50 years, the research agenda of clinical departments in teaching
      hospitals has broadened from one concerned primarily with physiologic studies to
      one that includes biochemistry, molecular biology, the quantitative analytic
      sciences, anthropology, and other social sciences. This memoir presents examples
      of such changes and provides examples of how the author's involvement has been
      promoted not only by his mentors, but also by those whom he has mentored.

PMID- 18723949
TI  - Beyond empathy.
AB  - Empathy is a highly desirable trait in a physician, but the term means different
      things to different people. Rather than focus on empathy, it may be more fruitful
      to consider the individual ingredients of a successful patient-physician
      engagement: scientific competency, imagination (the basis of empathy), caring
      about the patient, attentive (nonjudgmental) listening to the person's story, and
      skill in rewriting the illness story. The cardinal skill, on a sound base of
      scientific competence, is imagination. A successful engagement has beneficial
      consequences for physicians as well as patients.

PMID- 18723950
TI  - A clinicopathologic study of mantle cell lymphoma in a single center study in
      India.
AB  - We present clinical features, histopathology and results of treatment in cases of
      mantle cell lymphoma (MCL) at our hospital. We had 93 cases (2.1%) of MCL out of
      total 4301 cases of non-Hodgkin's lymphoma (NHL) in a 4-year period. It included
      68 cases (1.7%) of MCL from 3987 cases of NHL diagnosed on histopathology.
      Remaining 25 cases (7.9%) diagnosed solely on peripheral blood examination were
      excluded. Thirty-six (85%) patients had advanced-stage disease. Sixty-three were
      nodal and five were extranodal (all gastrointestinal tract). Common patterns were
      diffuse (64%), nodular (25%) and mantle zone type (11%). Sixty-two cases had
      lymphocytic while six had blastic morphology (all nodal). Tumor cells expressed
      CD20 (100%), CD43 (94%), CD5 (89%) and cyclin D1 (85%). Bone marrow was involved
      in 25 (59%) cases. Thirty-two patients could be treated. Median recurrence-free
      survival was 22.23 months. Diffuse pattern of nodal involvement had a lower
      overall survival.

PMID- 18723951
TI  - Angiogenesis in liver cirrhosis and hepatocellular carcinoma.
AB  - BACKGROUND: Angiogenesis has been well documented in hepatocellular carcinoma
      (HCC). As liver cirrhosis is considered preneoplastic condition, the aim of this
      study was to evaluate the process of angiogenesis using CD 34 as an endothelial
      cell marker in normal liver, cirrhosis and HCC. MATERIALS AND METHODS: A total of
      111 cases were included in this study, which consisted of 30 cases each of normal
      liver and cirrhosis that were all autopsy cases. Twenty-one cases of HCC included
      10 autopsy specimens, nine surgically resected specimens and two liver biopsies.
      Remaining were 30 cases of metastasis to the liver, which included 20 autopsy
      specimens, one surgically resected specimen and nine liver biopsies. The patients
      were between the age range from 17 to 80 years with 70 males and 11 females.
      Paraffin-embedded liver sections of all these cases were stained routinely by
      hematoxylin-eosin stain, while immunohistochemistry for CD 34 was performed for
      expression of endothelial cells. The positivity of CD 34 staining was evaluated
      by counting in 10 high-power field, grading was done from 0 to 4 and compared
      between normal liver, cirrhosis and HCC and metastasis. RESULTS: CD 34 was
      positive in 16/30 (53.3%) cases of cirrhosis, 18/21 (85%) cases of HCC and 26
      (86.6%) of metastasis to the liver. None of the normal liver showed any
      positivity. Grade 3 to 4 positivity was seen in 4/16 (25%) and 13/18 (72%) cases
      of cirrhosis and HCC, respectively. Amongst these, 10 were moderately
      differentiated, one well differentiated and rest two were fibrolamellar and
      sarcomatoid variants of HCC. CONCLUSION: Over expression of endothelial cell
      marker CD 34 with gradual progression was found from normal liver to cirrhosis to
      HCC and metastasis. Understanding of this process of angiogenesis might help in
      the design of efficient and safe antiangiogenic therapy for these liver
      disorders.

PMID- 18723952
TI  - Spectrum of pulmonary adenocarcinoma with ultrastructural correlation: an autopsy
      study from northern India.
AB  - BACKGROUND: In the present study, we have evaluated the use of electron
      microscopy in subtyping pulmonary adenocarcinomas, comparing the ultrastructural
      findings with the diagnosis rendered by light microscopy. MATERIALS AND METHODS:
      The gross and histologic features of 16 autopsy cases of pulmonary adenocarcinoma
      were analyzed and compared with electron microscopic features. The cytologic
      phenotypes of these cases of well-differentiated pulmonary adenocarcinoma were
      determined by electron microscopic examination. More than 200 cells in each case
      were examined, and the tumors were classified according to the predominant
      feature noted. RESULTS: Eight cases were of Clara cell origin and one case each
      of type II pneumocyte and bronchial surface cell type. The remaining 6 cases
      lacked definite discernible features of differentiation towards any specific cell
      type, other than presence of small nuclear clefts in occasional nuclei. Tumors
      with Clara cell differentiation were low cuboidal with apical snouts. Type II
      pneumocyte tumor failed to reveal any characteristic definable as light
      microscopic feature. CONCLUSION: Ultrastructural examination is the only definite
      means of identification of various cell types in the respiratory epithelium and
      hence forms an invaluable tool in classification of pulmonary adenocarcinoma.

PMID- 18723953
TI  - Mesangioproliferative glomerulonephritis: an important glomerulonephritis in
      nephrotic syndrome of young adult.
AB  - Mesangioproliferative glomerulonephritis (MesPGN) consists 10% of the total renal
      biopsy of glomerulonephritis. Aim of the present study was to find out
      clinicopathological changes in MesPGN and differences between diffuse and focal
      variety. MesPGN was seen mostly in young adults with mean age of 28.63 years for
      males and 26.3 years for females. Male predominance was noted (M:F ratio -
      1.4:1). About 70.83% patient presented with edema feet, followed by hypertension
      (29.19%), fever (16.66%), oliguria, nausea and vomiting (10.41%). Urine analysis
      in 50 patients revealed that 70% patients presented with nephrotic-range
      proteinuria, 36% patients with microscopic hematuria and 56% patients with
      leukocyturia. Statistically, no significant difference was found in clinical
      features of diffuse and focal MesPGN. Microscopic comparison between diffuse and
      focal variety showed that significant increase of focal glomerular basement
      membrane thickening, focal endothelial cell proliferation, focal smooth muscle
      hyperplasia, hyaline sclerosis and vasculitis was more common in diffuse variety.
      In focal variety, Capillary loop congestion, periglomerulitis, cloudy swelling
      and vacuolar degeneration in tubules were significantly more as compared to
      diffuse variety. Details of the clinical features, special laboratory tests and
      histological details revealed that diffuse variety had systemic diseases, which
      included Wegner's granulomatosis, microscopic polyangitis, Henoch's schonlein
      purpura, systemic lupus erythematosus (two cases) and one case each of Kimura's
      disease, pyelonephritis and tuberculosis. Only one case of focal MesPGN showed
      tuberculosis. Thus, our study concludes that MesPGN is an important cause of
      nephrotic syndrome among young adults. Secondly, search for some other diseases
      should be made and thirdly, if biopsy shows focal mesangial cell proliferations
      in minimal change glomerulonephritis (MCGN), it should be diagnosed as focal
      MesPGN rather than MCGN because these cases show recurrences.

PMID- 18723954
TI  - Pathology of pulmonary aspergillomas.
AB  - Aspergilloma refers to a fungal ball formed by saprophytic overgrowth of
      Aspergillus species and is seen secondary to cavitatory/cystic respiratory
      diseases. Paucity of clinical and pathological data of aspergilloma in India
      prompted us to analyze cases of aspergilloma over 15 years. The clinical features
      were recorded in all and correlated with detailed pathological examination.
      Aspergillomas were identified in 41 surgical excisions or at autopsy. There was
      male predominance; half the patients were in their fourth decade. Episodic
      hemoptysis was the commonest mode of presentation (85.4%). Forty aspergillomas
      were complex, occurring in cavitatory lesions (82.9%) or in bronchiectasis
      (14.6%). Simple aspergilloma was seen as an incidental finding in only one.
      Tuberculosis was the etiological factor in 31 patients, producing cavitatory or
      bronchiectatic lesions; other causes were chronic lung abscess and bronchiectasis
      (unrelated to tuberculosis). Surgical resections are endorsed in view of high
      risk of unpredictable, life-threatening hemoptysis.

PMID- 18723955
TI  - Morphometric evaluation of endometrial blood vessels.
AB  - Five hundred endometrial specimens were studied to document the changes in blood
      vessels in various phases of menstrual cycle, menstrual disturbances and in
      unexplained infertility. Sixty-three cases were taken as control and 437 cases as
      study group which included cases of dysfunctional uterine bleeding (DUB),
      endometrial polyps, fibroids, adenomyosis, infertility and atrophic endometrium.
      Using light microscopy, the vascular morphology was studied. The blood vessels
      were concentrated more in basal layer in the proliferative phase and in
      functional layer in the secretory phase. Cases of complex hyperplasia and pill
      endometrium had significantly higher vessel concentration. Congestion and
      dilatation of blood vessels were significantly higher in cases of DUB. The
      present study showed a positive correlation between endometrial angiogenesis and
      menstrual disorders. The alteration in blood vessel morphology has significant
      role in prognosis and in various anti-angiogenic therapies.

PMID- 18723956
TI  - Is seroprevalence of anti-IGM CMV among blood donors relevant in India?
AB  - BACKGROUND: Infection with cytomegalovirus (CMV) is more common in developing
      nations and the people belonging to the lower socioeconomic section of the
      society. The immunosuppressed population for whom CMV-seronegative blood products
      are requested is increasing due to advances in medical care. AIM: To study the
      prevalence of CMV antibodies among the different sexes and age groups in healthy
      blood donors. MATERIALS AND METHODS: A retrospective study was done on 5600 serum
      samples stored frozen in a repository for CMV antibodies using the ELISA
      technique. RESULTS: Five thousand three hundred and fifty (95.5%) were male and
      250 (4.5%) were female. Four cases (0.071%) out of 5600 samples were positive for
      anti-IgM CMV with 95% Confidence Interval (95% C.I) of 0.02 - 0.17. CONCLUSION:
      In a developing country like India, screening for IgM antibody on a routine basis
      may not be feasible, given the likely positive yield to be low and the cost being
      high. It is recommended that in a tertiary care hospital, blood units to be
      transfused to neonates, organ transplant recipients, those suffering from
      malignancies and other immunocompromised patients should be screened for anti-IgM
      CMV or preventive strategies like universal leucodepletion to be implemented to
      decrease the transmission of CMV in these groups of patients.

PMID- 18723957
TI  - Divergent strains of human immunodeficiency virus type 1 circulating in India,
      subtyped by heteroduplex mobility assay.
AB  - Genomic variations in HIV-1 represent a major problem in understanding disease
      progression, studying drug resistance and developing effective vaccines.
      Heteroduplex Mobility Assay (HMA) was used for analyzing HIV-1 subtypes resulting
      from genetic similarity or divergence of C2 -V3 -V5 region of envelope gene
      between HIV-1 strains obtained from clinical samples in a tertiary care center at
      Pune. DNA from the PBMCs of infected individuals was amplified by nested PCR.
      Heteroduplexes were then formed by denaturing DNA from the unknowns with DNA from
      the reference strains. The results were analyzed by polyacrylamide gel
      electrophoresis. Out of 177 samples analyzed, 170 were of subtype C (96%). Four
      samples were found to be of subtype B (2.2%); in three samples, no definitive
      assignment of subtype was possible by HMA and these perhaps could be circulating
      recombinant forms (CRFs) of HIV-1. These findings may have significant
      implications toward development of a candidate vaccine for India.

PMID- 18723958
TI  - Utility of lytic bacteriophage in the treatment of multidrug-resistant
      Pseudomonas aeruginosa septicemia in mice.
AB  - Drug resistance is the major cause of increase in morbidity and mortality in
      neonates. One thousand six hundred forty-seven suspected septicemic neonates were
      subjected for microbiological analysis over a period of 5 years. Forty-two P.
      aeruginosa were isolated and the antibiogram revealed that 28 P. aeruginosa were
      resistant to almost all the common drugs used (multidrug-resistant). The
      emergence of antibiotic-resistant bacterial strains is one of the most critical
      problems of modern medicine. As a result, a novel and most effective approaches
      for treating infection caused by multidrug-resistant bacteria are urgently
      required. In this context, one intriguing approach is to use bacteriophages
      (viruses that kill bacteria) in the treatment of infection caused by drug
      resistant bacteria. In the present study, the utility of lytic bacteriophages to
      rescue septicemic mice with multidrug-resistant (MDR) P. aeruginosa infection was
      evaluated. MDR P. aeruginosa was used to induce septicemia in mice by
      intraperitoneal (i.p.) injection of 10(7) CFU. The resulting bacteremia was fatal
      within 48 hrs. The phage strain used in this study had lytic activity against a
      wide range of clinical isolates of MDR P. aeruginosa. A single i.p. injection of
      3 x 10(9) PFU of the phage strain, administered 45 min after the bacterial
      challenge, was sufficient to rescue 100% of the animals. Even when treatment was
      delayed to the point where all animals were moribund, approximately 50% of them
      were rescued by a single injection of this phage preparation. The ability of this
      phage to rescue septicemic mice was demonstrated to be due to the functional
      capabilities of the phage and not to a nonspecific immune effect. The rescue of
      septicemic mice could be affected only by phage strains able to grow in vitro on
      the bacterial host used to infect the animals and when such strains are heat
      inactivated, they lose their ability to rescue the infected mice. Multidrug
      resistant bacteria have opened a second window for phage therapy. It would seem
      timely to begin to look afresh at this approach. A scientific methodology can
      make phage therapy as a stand-alone therapy for infections that are fully
      resistant to antibiotics.

PMID- 18723959
TI  - Prevalence of extended spectrum beta lactamase and AmpC beta lactamase producers
      among Escherichia coli isolates in a tertiary care hospital in Jaipur.
AB  - Resistance to broad spectrum beta lactams, mediated by extended spectrum beta
      lactamase (ESbetaL) and AmpC betaL enzymes is an increasing problem worldwide.
      Presence of these in clinical infections can result in treatment failure if one
      of the second or third generation cephalosporins is used. Therefore, it is
      recommended that any ESbetaL-producing organism according to the National
      Committee for Clinical Laboratory Standards (NCCLS) criteria can be reported as
      resistant to all extended spectrum beta lactam antibiotics regardless of the
      susceptibility test results. In this study, a total of 250 Escherichia coli (E.
      coli) isolates were subjected to Double disc test and AmpC disc test for the
      detection of ESbetaL- and AmpC betaL-producing strains, respectively. Prevalence
      of ESbetaL- and AmpC betaL-producing strains among E. coli isolates, over a 3
      month-period in the hospital-based population of Jaipur, was 64.80% (162/250).
      AmpC betaL producers were 24.00% (60/250) and co-existence of ESbetaL and AmpC
      betaL was detected in 8.00% (20/250) of the isolates.

PMID- 18723960
TI  - Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella
      pneumoniae in diabetic foot infections.
AB  - AIMS: Diabetic foot lesions are a major medical, social, and economic problem and
      are the leading cause of hospitalization for patients with diabetes, worldwide.
      ESBL-producing bacteria may not be detectable by routine disc diffusion
      susceptibility test, leading to inappropriate use of antibiotics and treatment
      failure. There is not much information on ESBL-producing organisms causing
      diabetic foot infection. An attempt was therefore made to study the ESBL
      producing Escherichia coli and Klebsiella pneumoniae in diabetic foot patients
      with type 2 diabetes mellitus. MATERIALS AND METHODS: A total of 134 isolates of
      E. coli and K. pneumoniae were obtained from tissue, pus swab, and wound swab
      samples from diabetic foot ulcers submitted for routine microbiological analysis
      during the period January to December 2005 from patients with diabetic foot
      infections who had type 2 diabetes mellitus, attending S. L. Raheja Hospital. The
      above isolates were tested for antimicrobial susceptibility by disc diffusion
      technique according to clinical and laboratory standards institute (CLSI)
      guidelines. The screening for ESBL production was done by phenotypic confirmatory
      test using ceftazidime disc in the presence and absence of clavulanic acid as
      recommended by CLSI. RESULTS: Among the 134 isolates, 54 (40.29%) were E. coli
      and 80 (59.70%) were K. pneumoniae; among which, ESBL production was detected in
      31 (23.13%) isolates. Of these 31, 15 (48.38%) were E. coli and 16 (51.61%) were
      K. pneumoniae. All the ESBL-producing isolates were found to be 100% sensitive to
      carbapenem (imipenem and meropenem). Mortality was found to be 3.22%, the cause
      of death being septicemia leading to multiple organ failure. CONCLUSIONS: The
      prevalence of ESBLs among members of Enterobacteriaceae constitutes a serious
      threat to the current beta-lactam therapy, leading to treatment failure and
      consequent escalation of costs. There is an urgent need to emphasize rational use
      of drugs to minimize the misuse of available antimicrobials.

PMID- 18723961
TI  - Novel route of infection in experimental model of hydatid disease.
AB  - Viable protoscolices of Echinococcus granulosus injected into Swiss-albino mice
      by two different routes, viz. intraperitoneal and subcutaneous and in two
      different concentrations of 2000 and 1000 scolices, to observe the development of
      cysts have shown that subcutaneous route of infecting a mouse model is superior
      because of its low infecting dose and longer survival period of mouse. This
      finding should be helpful in experiments to observe the effect of drugs for the
      treatment of hydatidosis, in vivo, without the need of killing the mouse.

PMID- 18723962
TI  - Phenotypic detection of inducible clindamycin resistance among Staphylococcus
      aureus isolates by using the lower limit of recommended inter-disk distance.
AB  - CONTEXT: Clindamycin is one of the important alternative antibiotics in the
      therapy of Staphylococcus aureus, particularly in methicillin-resistant S. aureus
      (MRSA) infections. Inducible clindamycin resistance (iMLS B--inducible Macrolide
      Lincosamide-Streptogramin B resistance) is a critical factor in antimicrobial
      susceptibility testing. AIMS: To know the rate of inducible clindamycin
      resistance among clinical isolates of Staphylococcus aureus in our hospital by
      Disk approximation test (D-test) using the average recommended inter-disk
      distance and comparing the results with that of D-test using the lower limit of
      recommended inter-disk distance. MATERIALS AND METHODS: A total of 51
      erythromycin-resistant and clindamycin-susceptible S. aureus isolates were
      subjected to disk approximation testing with 21 +/- 1 mm and 15 mm edge-to-edge
      distance between the clindamycin and erythromycin disks. STATISTICAL METHODS: Z
      test levels. RESULTS: Among 51 erythromycin-resistant and clindamycin-susceptible
      S. aureus isolates, 25 (49%) were recorded as inducible clindamycin resistant by
      D-test with 21 +/- 1 mm edge-to-edge distance between the clindamycin and
      erythromycin disks. When we re-tested all the 51 strains by D-test with 15 mm
      inter-disk distance, we identified 14% more iMLS B strains previously reported as
      D-test negative. Z-test for MRSA indicates that 15 mm edge-to-edge distance has
      significant advantage. CONCLUSIONS: Since the incidence of inducible clindamycin
      resistance is high (63% in our study), accurate identification of inducible
      clindamycin resistance is important to prevent therapeutic failure in infections
      caused by these strains. We suggest the use of D-test with 15 mm edge-to-edge
      inter-disk distance for detecting iMLS B .

PMID- 18723963
TI  - Evaluation of various screening tests to detect asymptomatic bacteriuria in
      pregnant women.
AB  - To evaluate the diagnostic efficacy of various screening tests in detecting
      asymptomatic bacteriuria among pregnant women. Clean catch midstream urine
      specimens were collected from 630 consecutive pregnant women and processed. Forty
      four (7.4%) of the urine samples were culture positive, with Escherichia coli as
      the predominant organism isolated (57.4%). The results of the four screening
      tests, viz., Gram's staining of uncentrifuged urine, pus cell count, nitrite test
      and leukocyte esterase (LE) test, were compared against urine culture. Gram's
      stain of the uncentrifuged urine was found to be the single most useful test with
      a sensitivity and negative predictive value (NPV) of 85.1% and 98.8%,
      respectively. Pus cell count was the least sensitive. Neither the nitrite test
      nor the LE test alone was sensitive enough with 74.4% and 61.7%, respectively.
      However, when either or both tests positive were considered, it increased the
      sensitivity and NPV comparable with Gram's staining results, with 82.9% and
      98.8%, respectively. With the potential to be used as an office diagnostic
      procedure, the combined nitrite and LE dipstick test may provide an acceptable
      alternative.

PMID- 18723964
TI  - Hepatic tuberculosis mimicking Klatskin tumor: a diagnostic dilemma.
AB  - Tubercular involvement of liver is rare and usually occurs in association with
      pulmonary or miliary tuberculosis, as diffuse involvement without recognizable
      pulmonary tuberculosis or rarely in a localized form, which presents as a
      tuberculoma or tubercular abscess. We report the case of a 22-year-old boy
      presenting with features of obstructive jaundice and a clinico-radiological
      picture highly suggestive of a perihilar cholangiocarcinoma (Klatskin tumor), but
      found to have tubercular involvement of porta hepatis. We review the literature
      on this unusual presentation, highlight the considerable diagnostic challenge
      such cases can pose, and also emphasize the need to consider tuberculosis in
      differential diagnosis of lesions involving the porta hepatis, particularly in
      areas endemic for the disease.

PMID- 18723965
TI  - Primitive neuroectodermal tumor of prostate.
AB  - Primitive neuroectodermal tumors (PNETs) are malignant proliferations of small,
      undifferentiated neuroectodermal cells occurring mainly in children and share the
      same reciprocal translocation between chromosomes 11 and 22 and the same patterns
      of biochemical and oncogene expression as osseus and extraosseus Ewing's sarcoma.
      Some PNETs occur in the brain, while others (the peripheral PNETs) occur in sites
      outside the brain, such as in the extremities, pelvis and the chest wall. They
      mostly originate in the chest, pelvis and retroperitoneum; in rare cases,
      occurrence in the head and neck area has also been seen. We present a rare case
      of primitive neuroectodermal tumor arising in the prostate gland in a 25-year-old
      male. To the best of our knowledge, this is the first documentation of a primary
      peripheral primitive neuroectodermal tumor in the prostate gland of any patient
      from India and rarely reported in English literature.

PMID- 18723966
TI  - Atypical teratoid/rhabdoid tumor of the central nervous system associated with
      congenital cataract.
AB  - Atypical teratoid /rhabdoid tumor (AT/RT) of the central nervous system is a rare
      but highly aggressive neoplasm that usually affects young children and infants
      and follows a rapidly fatal course. We report a case of AT/RT in a 3-month-old
      male infant who also had coincidental unilateral congenital cataract even though
      there was no associated congenital infectious disease.

PMID- 18723967
TI  - Primary marginal zone B-cell lymphoma of appendix.
AB  - Primary lymphomas of appendix are extremely rare tumors. The first case of
      primary lymphoma of appendix was reported by Warren in the year 1898. Incidence
      of primary lymphoma of appendix is 0.015% of all gastrointestinal lymphomas. This
      is a report of primary marginal zone B-cell lymphoma of appendix which presented
      as appendicular mass. As some cases are incidentally discovered, this case
      emphasizes that histological examination of all appendicectomy specimens is
      mandatory.

PMID- 18723968
TI  - Myofibroblastoma of breast.
AB  - Soft tissue neoplasms of breast thought to be derived from Myofibroblasts have
      been classified as myofibroblastomas. Myofibroblasts are spindle shaped
      mesenchymal cells derived from fibroblasts. These are rare neoplasms (more often
      seen in the male breast) and have same structural and immunohistochemical
      characteristics as those of solitary fibrous tumors. We present a case of an
      adult female presenting as firm breast lump diagnosed as myofibroblastoma and
      confirmed by diffuse positivity of CD34 immunohistochemical stain.

PMID- 18723969
TI  - Calcifying epithelial odontogenic tumor: report of two cases.
AB  - Calcifying epithelial odontogenic tumor (CEOT) is a rare, benign odontogenic
      tumor. It constitutes 0.4-3% of all odontogenic tumors. There is only a single
      case, which has been reported in the Indian literature that too in cytology.
      Microscopically, these are composed of large sheets of epithelial cells,
      amorphous amyloid-like material and calcification. Although these lesions are
      benign, they can be locally aggressive, but malignant transformation and
      metastasis is rare. Considering its locally aggressive nature, appropriate
      management and long-term follow-up is recommended. We describe two cases of CEOT
      involving the hard palate and leading to facial alterations.

PMID- 18723970
TI  - Osseous metaplasia in renal cell carcinoma: report of a rare case.
AB  - Focal calcifications are frequently seen in renal masses including renal cell
      carcinoma (RCC). Osseous metaplasia, on the other hand, is a rare finding in RCC.
      We report a case of RCC with radiological evidence of speckled calcification that
      showed osseous metaplasia on histopathological examination. The clinical and
      pathologic differential diagnosis for this tumor is discussed along with a review
      of the literature on this unusual phenomenon.

PMID- 18723971
TI  - Cytomegalovirus infection with lissencephaly.
AB  - Lissencephaly is a malformation of the brain in which the brain surface is
      smooth, rather than convoluted. Among the various causes of lissencephaly,
      infection by a virus during pregnancy plays an important role. Cytomegalovirus
      (CMV) is an important pathogen causing this anomaly. We present this case of a
      young female with 24-week-gestation diagnosed on ultrasound as carrying an
      anomalous fetus with lissencephalic features. At autopsy, there were multiple
      intra-nuclear CMV inclusions in the brain and the kidneys. This case is presented
      for its rarity and for the documentation of the tissue localization of CMV
      inclusions at autopsy.

PMID- 18723972
TI  - Testicular granulosa cell tumor, adult type.
AB  - Granulosa cell tumor (GCT) of the adult type is a rare and slow-growing neoplasm
      in the testis. This tumor may be associated with endocrine manifestations and
      resemble classic GCT of the ovary morphologically. It has a potential for distant
      metastasis or recurrence late in the clinical course. We report a case of
      granulose cell tumor of the testis, adult type.

PMID- 18723973
TI  - Mucosa-associated lymphoid tissue lymphoma in conjunctiva.
AB  - A case of primary mucosa-associated lymphoid tissue (MALT) lymphoma (marginal
      zone B-cell lymphoma of MALT according to WHO classification) in conjunctiva,
      which presented as a slowly growing salmon-colored mass at limbus of left eye is
      reported. Histological examination revealed a diffuse low-grade lymphoma.
      Immunohistochemical analysis using monoclonal antibodies showed that the tumor
      cells are leukocyte common antigen (CD45)+, CD20+, CD3-, CD5-, CD10- and CD43-,
      which confirmed the B-cell lineage of lymphoma. The case is being reported for
      its rarity and clinical importance of recognizing such cases because of excellent
      prognosis.

PMID- 18723974
TI  - Primary renal fibrosarcoma: a rare case report and review of literature.
AB  - Primary renal fibrosarcoma is a rare tumor. We describe a case of primary renal
      fibrosarcoma in a 54-year-old male who presented with abdominal lump and
      intermittent hematuria.

PMID- 18723975
TI  - Lymphangiectasia of small intestine presenting as intussusception.
AB  - Intussusception is defined as telescoping of a segment of gastrointestinal tract
      into an adjacent one. In small children, it is the commonest cause of intestinal
      obstruction. More than 90% of childhood intussusceptions are idiopathic. We
      report a rare case of localized small intestinal lymphangiectasia, presenting as
      intussusception in a 6-month-old male child. The child presented with features of
      acute intestinal obstruction for which he was later operated. The gross
      examination of excised ileocecal mass revealed intussusception. Histopathologic
      examination revealed lymphangiectasia of small intestine, which acted as a lead
      point for ileocecal intussusception. Postoperative period was uneventful.

PMID- 18723976
TI  - Palisaded myofibroblastoma of lymph node.
AB  - A 60-year female was presented with swelling in the left inguinal region.
      Microscopically, the left inguinal lymph node shows typical "amianthoid" fibers
      (hyalinized areas), spindle cell fascicles and hemorrhagic areas in the
      interstitial spaces with rim of lymphoid tissue. Preoperatively, patient was non
      reactive for HIV I and II. This lesion is usually mistaken as neurilemmoma and
      Kaposi's sarcoma.

PMID- 18723977
TI  - Localized amyloidosis of the urinary bladder, clinically masquerading as bladder
      cancer.
AB  - Amyloidosis is characterized by extracellular deposition of a proteinaceous,
      hyaline material. Localized deposition of amyloid in individual organs is
      uncommon. It can occur in the absence of systemic involvement. Herein, we
      describe two cases of localized amyloidosis of the urinary bladder, which
      clinically, radiologically, and on cystoscopy masqueraded as bladder cancer. A
      diagnosis of amyloidosis in both these cases was ascertained on biopsy,
      supplemented with special stains.

PMID- 18723978
TI  - Parvovirus-induced dyserythropoeisis in a child.
AB  - Most persons with parvovirus B19 infection are asymptomatic or exhibit mild,
      nonspecific, cold-like symptoms. However, hematologic problems associated with
      the infection include transient aplastic crisis, chronic red cell aplasia, mild
      neutropenia and thrombocytopenia. A rare hematologic manifestation is in the form
      of dyserythropoeisis. Herein, we present the case of a 9-year-old female with
      severe dyserythropoeisis associated with parvovirus infection.

PMID- 18723979
TI  - Bilateral angiosarcoma breast diagnosed by fine needle aspiration cytology.
AB  - Concurrent or synchronous angiosarcoma (AS) of breast is a rarity. Specific
      recognition of this neoplasm in cytological specimens is difficult and conclusive
      diagnosis in the absence of ancillary methods is achieved only uncommonly.
      Herein, we present a case of bilateral AS of breasts in a 32-year-old lady
      diagnosed by fine needle aspiration (FNA) cytology, thus enabling a definitive
      surgical approach. This case report emphasizes that when aspiration smears show
      vasoformative features consisting of microacini, arborizing microtissue fragments
      and intracytoplasmic lumen against a bloody background, diagnosis can be made
      conclusively by FNA with immunohistochemical confirmation.

PMID- 18723980
TI  - Diagnosis of metastatic carcinoid in mesenteric lymph node by fine needle
      aspiration cytology.
AB  - Although carcinoid tumor is a relatively common neoplasm in surgical pathology,
      fine needle aspiration cytology (FNAC) as a method of primary diagnosis has only
      been reported a few times. We report the case of a 55-year-old male patient who
      presented with colicky pain in the abdomen and a vague mass in the right lumbar
      region. Ultrasonographic study showed an enlarged mesenteric lymph node.
      Ultrasonography-guided FNAC revealed cellular smears with neuroendocrine cellular
      arrangement and morphology. The cytomorphologic characteristics of carcinoid
      tumors are distinctive enough for diagnosis. A diagnosis of metastatic carcinoid
      was given. 5-hydroxyindolacetic acid in 24-hour urine turned out to be high.
      Histopathology and immunohistochemistry studies also confirmed the diagnosis.
      Thus, FNAC can be a useful and safe tool in the diagnosis of carcinoid tumors.

PMID- 18723981
TI  - Cytodiagnosis of angiosarcoma of breast.
AB  - A 24-year-old female presented with swelling in the left breast for one-and-a
      half years associated with pain for last 4 months. During this period, she was
      operated twice and once again there was local recurrence, the biopsy was
      interpreted as benign vascular lesion. The case was diagnosed by preoperative
      cytology as angiosarcoma of breast, after which, she underwent modified radical
      mastectomy. Angiosarcoma of breast is uncommon with extremely bad prognosis.
      Familiarity with the clinical and pathologic features is critical in avoiding
      underdiagnosis and delayed treatment.

PMID- 18723982
TI  - Follicular thyroid carcinoma with metastasis to skin diagnosed by fine needle
      aspiration cytology.
AB  - In April 2006, a 55-year-old female presented with a thyroid mass and multiple
      skin nodules on scalp, forehead and neck. Fine needle aspiration cytology of
      thyroid mass and multiple skin nodules show tumor cells clusters in a repetitive
      microfollicular pattern on May-Grunwald-Giemsa stain suggestive of follicular
      thyroid carcinoma with metastasis to skin. Although follicular carcinoma have a
      propensity for vascular invasion and hematogenous dissemination, skin is not
      commonly involved. Only a few cases of cutaneous metastasis from follicular
      thyroid carcinoma are reported in the English language literature.

PMID- 18723983
TI  - Sporotrichoid pattern of cutaneous nocardiasis due to Nocardia asteroids.
AB  - Cutaneous nocardiosis is a rare disease, only a few cases of which have been
      reported from the world as well as in India. This infection, when in the
      lymphocutaneous form, may clinically resemble sporotrichosis, hence causing a
      diagnostic dilemma. Here, we report a case of primary cutaneous, sporotrichoid
      pattern of cutaneous nocardiosis caused by Nocardia asteroides in immunocompetent
      host. The patient was a 32-year-old farmer, with no predisposing factors, who
      presented with cutaneous nocardiosis. The diagnosis was confirmed by culture of
      the biopsy, after which the patient was treated successfully with antibacterial
      agents.

PMID- 18723984
TI  - Isolated frontal sinusitis due to Pseudallescheria boydii.
AB  - We report a case of recurrent sino-nasal fungal infection due to Pseudallescheria
      boydii (P. boydii) in a 33-year-old diabetic woman. It is very essential to
      identify P. boydii, as Miconazole is the only antifungal drug of choice. However,
      histological examination of the specimen for clinching clues such as intercalary
      conidia and chlamydoconidia plays an important role in identifying P. boydii,
      when fungal culture fails to yield the growth. On follow-up, the woman responded
      for the treatment with Miconazole and is free of symptoms, with no recurrence
      after 6 months.

PMID- 18723985
TI  - Does acute promyelocytic leukemia in Indian patients have biology different from
      the West?
AB  - Acute promyelocytic leukemia (APML) is a well-characterized malignancy with
      typical clinico-hematological and molecular features. However, Indian data on
      this malignancy are limited. This study was conducted to determine the clinico
      hematological profile of APML in India. Thirty-five patients with APML presenting
      to Hematology Department, AIIMS, New Delhi, between July 2003 and June 2005 were
      evaluated for presenting clinical features, hemogram, peripheral smear, bone
      marrow morphology and cytochemistry. Reverse transcriptase PCR (RT-PCR) for PML
      RARalpha was done in all cases. Male-to-female ratio was 0.9:1 (males--17 and
      females--18) with median age 25 years (range 11-57 years). Presenting features
      included anemia, bleeding, fever, gum hypertrophy and scrotal ulceration. All
      cases showed hypergranular abnormal promyelocytes. Median hemoglobin was 6.3 g/dL
      (range - 3.0-9.0 g/dL), total leukocyte count (TLC) was 33.88 x 10(9) /L (range -
      1-170 x 10(9) /L). Platelet count was 28 x 10(9) /L (range - 4-170 x 10(9) /L).
      All cases were positive for myeloperoxidase and sudan black (SB), whereas 60%
      cases also showed non specific esterase (NSE) positivity with 40% cases being
      fluoride sensitive. RT-PCR showed PML-RARalpha in 33/35 cases with the bcr3
      isoform being present in 24/33 positive cases (72.7%). The two cases negative for
      PML-RARalpha showed typical morphology and responded to ATRA. On statistical
      analysis, no correlation was found between bcr isoform and TLC, platelet count,
      age sex and early death. Unusual features included gum hypertrophy and scrotal
      ulceration at presentation and high median presenting TLC (33.8 x 10(9) /L).
      There was, however, no microgranular variant. Another interesting feature was a
      high incidence of NSE positivity (60%), which was fluoride sensitive in 40%.
      Moreover, the bcr3 isoform was significantly overexpressed (72.7%) in comparison
      to other studies. APML in India has certain unusual features, which may reflect a
      different biology.

PMID- 18723986
TI  - Isolated giant tuberculoma of the liver.

PMID- 18723987
TI  - Plasmablastic multiple myeloma with Dutcher bodies.

PMID- 18723988
TI  - Presacral medulloepithelioma.

PMID- 18723989
TI  - Sclerosing stromal tumor: unusual histologic features of a rare ovarian tumor.

PMID- 18723990
TI  - Schwannoma of nasal cavity with intracranial extension: a rare but interesting
      phenomenon in a benign neoplasm.

PMID- 18723991
TI  - Leiomyosarcoma of the vulva.

PMID- 18723992
TI  - Desmoplastic small round cell tumor--abdomen.

PMID- 18723993
TI  - Carcinoma cervix with atypical presentation of metastatic lesion as a cyst in the
      right deltoid muscle.

PMID- 18723994
TI  - Lymphoid aggregates in bone marrow biopsies in patients with hypereosinophilia.

PMID- 18723995
TI  - Solitary fibrous tumor of the orbit.

PMID- 18723996
TI  - Synchronous schwannomas not associated with neurofibromatosis.

PMID- 18723997
TI  - Primary plasma cell leukemia in a 30-year-old woman.

PMID- 18723998
TI  - Multilocular cystic renal cell carcinoma: a diagnostic rarity.

PMID- 18723999
TI  - Xanthogranulomatous cervicitis.

PMID- 18724000
TI  - The significance of cell block and fine needle aspiration cytology in diagnosing
      a rare presentation of hepatocellular carcinoma.

PMID- 18724001
TI  - Prevalence of HCV and HBV infection in liver disorders in the Aligarh region of
      western Uttar Pradesh.

PMID- 18724002
TI  - Occult malignant melanoma metastasizing to the stomach in an elderly patient.

PMID- 18724003
TI  - Steroid cell tumor, NOS, of ovary.

PMID- 18724004
TI  - Effect of dried-bonito broth on mood states: a pooled analysis of four randomized
      controlled human trials.
AB  - Dried-bonito broth is commonly employed as a soup and sauce base in Japanese
      cuisine and is considered to be a nutritional supplement that promotes recovery
      from fatigue. Previous human trials have indicated that the ingestion of dried
      bonito broth improves several mood states including fatigue, however, the effects
      in these studies have differed. The aim of this study was to clarify the effects
      of daily ingestion of dried-bonito broth on mood states by a pooled analysis of
      the randomized placebo-controlled trials. Five comparisons in four trials were
      selected for the pooled analysis (n = 159). The ingestion of dried-bonito broth
      significantly decreased the scores for fatigue (P = 0.032) and increased those
      for vigor (P = 0.027) compared to the placebo ingestion, suggesting that the
      dried-bonito broth improved fatigue felt in daily life. Furthermore, the
      ingestion of dried-bonito broth decreased the scores for tension-anxiety (P =
      0.004) and confusion (P = 0.008) compared to the placebo ingestion. The ingestion
      of dried-bonito broth also significantly decreased the scores for total mood
      disturbance (P = 0.005). These results suggest that the ingestion of dried-bonito
      broth improves mood states especially fatigue, vigor, tension-anxiety and
      confusion.

PMID- 18724005
TI  - VEGF and M-CSF levels in periodontal tissue during tooth movement.
AB  - It has been reported that both vascular endothelial growth factor (VEGF) and
      macrophage colonystimulating factor (M-CSF) can induce osteoclast recruitment.
      Thus, VEGF and M-CSF are considered to be closely involved in the bone remodeling
      process. The purpose of this study was to evaluate changes in VEGF and M-CSF
      expression during orthodontic treatment. The expression of VEGF and M-CSF mRNA in
      osteoblasts and fibroblasts was detected by in situ hybridization during
      experimental tooth movement in mice. Furthermore, the canine retraction side and
      the control side of orthodontic patients were compared, revealing a statistically
      significant increase in both VEGF and M-CSF concentrations in gingival crevicular
      fluid. These results suggest that orthodontic tooth movement causes an increase
      in VEGF and M-CSF levels. These factors may induce bone remodeling via
      osteoclastic bone resorption.

PMID- 18724006
TI  - The effects of dexmedetomidine on human neutrophil apoptosis.
AB  - The purpose of the present study was to evaluate the effect of dexmedetomidine,
      used as a sedative in the intensive care unit, on human neutrophil apoptosis and
      superoxide production in vitro. Neutrophils from healthy volunteers were
      incubated in different concentrations of dexmedetomidine (1, 10 and 100 ng/mL).
      Apoptosis was assessed by Hoechst 33342 staining, caspase activities and loss of
      mitochondrial transmembrane potential (MTP). Superoxide production was determined
      by the WST-1 assay. After 24 h of incubation, dexmedetomidine accelerated
      neutrophil apoptosis in a dose-dependent manner and 100 microM yohimbine did not
      inhibit the apoptosis. Treatment with 100 ng/mL of dexmedetomidine significantly
      enhanced the activation of caspases-3/7, -8 and -9, and also markedly increased
      the number of neutrophils with decreased MTP. At 24 h, the suppression of
      superoxide production was dependent on dexmedetomidine concentrations. However, a
      clinically relevant concentration (1 ng/mL) of dexmedetomidine did not affect
      neutrophil apoptosis and superoxide production. These results suggest that high
      doses of dexmedetomidine induce apoptosis without alpha(2)-adrenoceptors stimulus
      and inhibit superoxide production after long-term incubation. The mechanisms of
      dexmedetomidine-induced apoptosis are associated with the caspase cascade and
      loss of MTP.

PMID- 18724007
TI  - Changes of HCN gene expression and I(f) currents in Nkx2.5-positive
      cardiomyocytes derived from murine embryonic stem cells during differentiation.
AB  - Changes in the expression of hyperpolarization-activated cyclic nucleotide (HCN)
      gated channels and I(f) currents during the differentiation of embryonic stem
      cells into cardiac cells remain unknown. We examined changes of HCN genes in
      expression and function during the differentiation of Nkx2.5-positive cardiac
      precursor cells derived from mouse ES cells using cell sorting, RTPCR,
      immunofluorescence and whole cell patch-clamp techniques. Cs(+)-induced
      inhibition of automaticity and transcription of HCN genes increased during
      differentiation. Expressions of Nkx2.5, a marker of cardiac progenitor cell, and
      Flk1, a marker of hemangioblast, were mutually exclusive. Messenger RNA and
      proteins encoded by HCN1 and 4 genes were predominantly observed in Nkx2.5
      positive cells on day 15, although Flk1-positive cells did not express genes of
      the HCN family on that day. Cs(+)-induced prolongation of the cycle of
      spontaneous action potentials and I(f) currents were predominantly observed on
      day 15. These results suggested that a fraction of Nkx2.5-positive cardiac
      precursor cells was committed to pacemaking cells expressing I(f) channels
      predominantly encoded by HCN 1 and 4 genes.

PMID- 18724008
TI  - Chick spinal accessory lobes contain functional neurons expressing voltagegated
      sodium channels generating action potentials.
AB  - Ten pairs of protrusions, called accessory lobes (ALs), exist at the lateral
      sides of avian lumbosacral spinal cords. Histological evidence has shown that
      neurons are present in AL and behavioral evidence suggests that AL acts as a
      sensory organ of equilibrium during bipedal walking. However, there is little
      functional evidence to indicate that cells in AL have neuronal functions. To
      elucidate this point, we developed a method to dissociate cells from chick AL and
      made electrophysiological recordings with the whole-cell patch clamp technique.
      Cells dissociated by enzymatic digestion from chick AL contained two major types
      of cells. One was round with clear cytosol and the other had a round cell body,
      rich cytosolic structures and some processes. Rapidly activating inward currents
      and slowly activating outward currents were recorded in response to depolarizing
      pulses to -10 mV under the voltage clamp configuration only from the latter type
      of cells. TTX at 100 nM inhibited the inward current by 85%, indicating the
      functional expression of TTX-sensitive voltage-gated Na(+) channel (VGSC).
      Activation and inactivation kinetics of the inward currents in AL cells were
      similar to those of mammalian VGSC. The VGSC-expressing AL cells generated action
      potentials in response to depolarization under the current clamp configuration.
      These results clearly indicate that functional neurons expressing fast
      inactivating and TTXsensitive VGSC which generate action potentials exist in the
      AL of the chick. These lines of cellular evidence clearly indicate that
      functional neurons exist in ALs and further support the proposal that the chick
      ALs function as the sensory organ of equilibrium.

PMID- 18724009
TI  - Molecular effects of the tissue-nonspecific alkaline phosphatase gene
      polymorphism (787T > C) associated with bone mineral density.
AB  - Based on studies of hypophosphatasia, which is a systemic skeletal disorder
      resulting from tissuenonspecific alkaline phosphatase (TNSALP) deficiency, TNSALP
      was suggested to be indispensable for bone mineralization. Recently, we
      demonstrated that there was a significant difference in bone mineral density
      (BMD) among haplotypes, which was lowest among TNSALP (787T [Tyr-246Tyr])
      homozygotes, highest among TNSALP (787T > C [Tyr246His]) homozygotes, and
      intermediate among heterozygotes. To analyze protein translated from the TNSALP
      gene 787T > C, we performed the biosynthesis of TNSALPs using TNSALP cDNA
      expression vectors. TNSALP (787T) and TNSALP (787T > C) were synthesized
      similarly as a high-mannose-type 66-kDa form, becoming an 80-kDa form. Expression
      of the human 787T > C TNSALP gene using the cultured mouse marrow stromal cell
      line ST2 demonstrated that the protein translated from 787T > C exhibited an ALP
      specific activity similarly to that of 787T. Interestingly, the Km value for
      TNSALP in ST2 cells transfected with the 787T > C TNSALP gene was decreased
      significantly compared to that of cells carrying the 787T gene (P < 0.01). These
      results suggest that the significant difference in Km values between the proteins
      translated from 787T > C and 787T may contribute to regulatory effects on bone
      metabolism.

PMID- 18724010
TI  - The effects of examination stress on salivary cortisol, immunoglobulin A, and
      chromogranin A in nursing students.
AB  - This study aimed to assess the effects of examination stress on salivary
      cortisol, immunoglobulin A (IgA), and chromogranin A (CgA) in nursing students.
      Saliva samples were collected from 15 healthy females before and immediately
      after the one-hour examination, and two hours after the examination. Salivary
      cortisol, IgA, and CgA concentrations were determined by enzyme-linked
      immunosorbent assay. Both IgA and CgA concentrations statistically increased
      immediately after the examination (P < 0.05) and decreased two hours after the
      examination. No significant differences were observed between before and after
      the examination in the salivary cortisol concentration. These findings suggest
      that the acute stress due to the examination is associated with raised salivary
      IgA and CgA, but not cortisol.

PMID- 18724011
TI  - Primary percutaneous coronary intervention vs conservative treatment for acute ST
      elevation myocardial infarction: short- and long-term follow-up according to
      disease severity.
AB  - BACKGROUND: Because there is insufficient evidence to support primary
      percutaneous coronary intervention (PPCI) as the treatment of acute myocardial
      infarction (AMI), this study elucidated the efficacy of PPCI according to disease
      severity. METHODS AND RESULTS: Between January 1999 and June 2001, 3,021 AMI
      patients were registered at Tokyo Women's Medical University and 17 affiliated
      institutions. Of these, 1,994 patients with ST-elevation AMI were admitted within
      12 h of onset. PPCI was performed in 1,143 and 294 were treated conservatively.
      The 1,437 patients were grouped according to Thrombolysis In Myocardial
      Infarction-risk score: PPCI was performed in 59.5% of the low-risk group, 61.8%
      of the moderate-risk group, and 56.2% of the high-risk group. Cardiac death was
      the primary outcome. In the low-risk group, no significant differences were
      observed between PPCI and conservative therapy for 30-day and long-term cardiac
      mortality rates. In the moderate-risk group, the 30-day cardiac mortality rate
      for PPCI was significantly lower; however, no significant intergroup differences
      were observed for long-term cardiac mortality. In the high-risk group, 30-day and
      long-term cardiac mortality for PPCI were significantly more favourable than for
      conservative therapy (p<0.001 and p=0.0032, respectively). CONCLUSIONS: Although
      PPCI strongly correlated with low short- and long-term cardiac mortality rates in
      high-risk AMI patients, no similar correlation was found in low-risk patients.

PMID- 18724012
TI  - Demographics and changes in medical/interventional treatment of coronary artery
      disease patients over a 3.5-year period in Japan: the Japanese Coronary Artery
      Disease Study: trend examination.
AB  - BACKGROUND: Cardiovascular medicine has undergone rapid changes in recent years,
      but there are insufficient reports using large cohorts regarding these changes
      for Japanese coronary artery disease (CAD) patients. Hence, a large-scale
      prospective observational study was needed. METHODS AND RESULTS: A total of
      36,298 patients were registered over 6 periods. Patients with hypertension,
      hyperlipidemia, obesity, and impaired glucose tolerance increased in number,
      while those with old myocardial infarction (MI), smoking habit, and family
      history of CAD decreased. Regarding the trends in interventional procedures,
      stent use increased in both the whole cohort and the acute MI subgroup, while the
      use of only medical control decreased. Regarding prescription trends, angiotensin
      receptor blockers increased while nitrates decreased. CONCLUSIONS: In a period of
      3.5 years, significant changes were observed for both interventional procedures
      and medication, which might be related to the well-timed compliance of physicians
      with published evidence. However, these changes were not related to changes in
      the event rates, at least over the short term. Although careful attention should
      be paid in interpreting the results, because this is an observational study and
      the background of patients in each cohort might have been heterogeneous, such
      investigations should be constantly conducted for evidence-based practice.

PMID- 18724013
TI  - Intensive pharmacologic treatment in patients with acute non ST-segment elevation
      myocardial infarction who did not undergo percutaneous coronary intervention.
AB  - BACKGROUND: The aim of this study was to assess the impact of more aggressive
      pharmacological treatment on short-term clinical outcomes in patients with acute
      non ST-segment elevation myocardial infarction (NSTEMI) who do not undergo
      percutaneous coronary intervention (PCI). METHODS AND RESULTS: The 924 NSTEMI
      patients treated with early conservative strategy (69.2+/-12.5 years, 637 males)
      in 50 hospitals that were high-volume centers with facilities for primary PCI
      were recruited to the Korean Acute Myocardial Infarction Registry (KAMIR) from
      November 2005 to August 2007. For all patients, the pharmacotherapy index based
      on the use of drugs during hospital stay was assessed (range of points 0-10).
      Primary endpoint was the combined in-hospital mortality and morbidity and major
      adverse cardiac events during 1 month of clinical follow-up. Of the patients,
      data from 847 who were followed-up for 1 month after discharge were analyzed. The
      rate of the primary endpoint decreased with an increase of the pharmacotherapy
      index and this result was similar in the low- and high-risk groups. In the
      multivariate analysis, low pharmacotherapy index (<or=4 points) was an
      independent predictor of the primary endpoint. CONCLUSIONS: More intensive
      pharmacological treatment may improve short-term clinical outcomes in acute
      NSETMI patients who do not undergo PCI.

PMID- 18724014
TI  - Clinical outcomes and therapeutic strategy in patients with acute myocardial
      infarction according to renal function: data from the Korean Acute Myocardial
      Infarction Registry.
AB  - BACKGROUND: The aim of the present study was to evaluate the relationship between
      clinical outcomes after acute myocardial infarction (MI) and renal function by
      glomerular filtration rate (GFR) in patients with normal or mildly elevated serum
      creatinine concentrations. METHODS AND RESULTS: As part of the Korean Acute
      Myocardial Infarction Registry (KAMIR), 6,834 acute MI patients with a serum
      creatinine concentration of <or=2.0 mg/dl were enrolled from November 2005 to
      December 2006. The renal function was stratified arbitrary to 5 groups: (1)
      normal function, >90.0; (2) preserved function, 75.0-89.9; (3) mild dysfunction,
      60.0-74.9; (4) moderate dysfunction, 45.0-59.9; (5) severe dysfunction, <45
      ml.min(-1). 1.73 m(-2). Clinical characteristics, mortality and adverse events
      were analyzed among each group. Although reperfusion and medical therapies were
      underused, the rates of mortality and adverse events were increased with
      declining renal function. After adjustment with confounders, severe and moderate
      renal dysfunctions were important risk predictors of in-hospital mortality, long
      term mortality and adverse events. CONCLUSION: The spectrum of renal function,
      when it was presented by GFR, is broad and is an important risk predictor for
      adverse outcomes after acute MI, even in patients with normal or mildly elevated
      serum creatinine concentrations. Furthermore, standard treatments were underused
      in any degree of renal dysfunction.

PMID- 18724015
TI  - Hypertension is the most important component of metabolic syndrome in the
      association with ischemic heart disease in Taiwanese type 2 diabetic patients.
AB  - BACKGROUND: To evaluate the association between components of metabolic syndrome
      (MS) and ischemic heart disease (IHD) in Taiwanese patients with type 2 diabetes
      mellitus (T2DM). METHODS AND RESULTS: A total of 1,296 (604 men and 692 women)
      subjects with T2DM aged 62.5+/-11.7 (14-87) years were studied. MS was defined
      using the World Health Organization modified criteria and included more than 2 of
      hypertension, obesity, dyslipidemia and microalbuminuria. IHD was diagnosed
      through history or ischemic electrocardiogram according to the Minnesota codes.
      Results showed that MS was present in 76.2% and IHD in 36.3% of the patients,
      respectively. MS increased with age for both sexes, but there was no difference
      between men and women in the age groups of <45, 45-54 and 55-64 years. However,
      the prevalence of MS was significantly higher in women (87.7% vs 78.0%) in the
      age group>or=65 years. IHD prevalence was significantly higher in patients with
      MS, hypertension, dyslipidemia and obesity (p<0.01), and was higher with
      borderline significance for microalbuminuria (0.05<p<0.1). The respective age
      adjusted odds ratios were 3.61 (2.57-5.08), 7.10 (5.38-9.38), 1.70 (1.32-2.18),
      1.75 (1.33-2.28), and 1.11 (0.88-1.41). CONCLUSIONS: The prevalence of MS in
      subjects with T2DM is high and increases with age. The impact of different risk
      factors on IHD is diverse, with hypertension being the most important.

PMID- 18724016
TI  - Effect of intra-coronary nicorandil administration prior to reperfusion in acute
      ST segment elevation myocardial infarction.
AB  - BACKGROUND: Intravenous nicorandil infusion with percutaneous coronary
      intervention (PCI) has been reported to reduce reperfusion injury events and
      improve cardiac function in patients with acute myocardial infarction (MI).
      However, there is limited information on the use of intracoronary nicorandil.
      METHODS AND RESULTS: In the present study, 73 patients with acute ST segment
      elevation MI undergoing PCI were randomly assigned to the Nicorandil Group (n=37)
      or the Control Group (n=36). The composite endpoints were the incidences of
      ventricular arrhythmia, no-reflow and slow flow. A significant difference in the
      composite endpoint was observed in the Nicorandil Group when compared with the
      Control Group (p=0.037). The occurrence of post Thrombolysis In Myocardial
      Infarction (TIMI) grade 3 was significantly higher in the Nicorandil Group
      (p=0.019). Major adverse cardiac events during hospitalization and within 30 days
      of treatment were similar between the 2 groups. CONCLUSION: Administration of
      intracoronary nicorandil reduced the occurrence of no-reflow, slow reflow, and
      reperfusion arrhythmia, and improved the myocardial perfusion grade, TIMI flow
      during PCI and improved clinical outcomes in patients with acute MI.

PMID- 18724017
TI  - One-year clinical outcomes of dialysis patients after implantation with sirolimus
      eluting coronary stents.
AB  - BACKGROUND: The efficacy of sirolimus-eluting stents (SESs) has not been
      established in dialysis patients. METHODS AND RESULTS: This study was a non
      randomized observational single-center registry in a community hospital: data for
      80 consecutive dialysis patients who underwent percutaneous coronary intervention
      (PCI) with SES were compared with those of a historical group of consecutive 124
      dialysis patients treated with bare-metal stents (BMS). After 1 year, the
      cumulative incidence of major adverse cardiac events (MACE), comprising cardiac
      death, nonfatal myocardial infarction, stent thrombosis, or target lesion
      revascularization (TLR), was 25.2% in the SES group and 38.2% in the BMS group
      (p=0.048). In multivariate analysis, use of SES remained an independent predictor
      of MACE at 1 year after PCI (risk ratio 0.70, 95% confidence interval 0.52-0.93,
      p=0.015). Rates of TLR were 21.7% in the SES group and 30.9% in the BMS group and
      (p=0.15). Subgroup analysis showed that use of SES was effective in patients with
      small vessels, non-diabetic patients, and patients without highly calcified
      lesions. CONCLUSIONS: In dialysis patients, the implantation of SES was
      moderately effective in reducing MACE at 1 year after PCI as compared with BMS.
      However, the TLR rate at 1 year was relatively higher than previously reported.

PMID- 18724018
TI  - Health-related quality of life of outpatients with systolic and isolated
      diastolic dysfunction: Sado Heart Failure Study.
AB  - BACKGROUND: The impact of isolated diastolic dysfunction (IDD) and systolic
      dysfunction (SD) on health-related quality of life (HRQOL) is unknown. METHODS
      AND RESULTS: To evaluate HRQOL in patients with IDD and SD under treatment,
      information on outpatients aged 60-84 years was extracted from the records of
      4,500 consecutive individuals who underwent echocardiographic examination at Sado
      General Hospital. The medical records of these patients were reviewed and a
      questionnaire, including the Medical Outcome Study Short Form 36, was mailed to
      71 IDD and 99 SD patients; answers were obtained from 66 and 91 patients,
      respectively. The HRQOL of patients with cardiac dysfunction was impaired even
      when echocardiographic parameters improved with treatment. Patients with IDD
      showed an impairment of HRQOL similar to those with SD. Compared with males,
      female patients had a larger and more significant reduction in the physical and
      mental components of the HRQOL score. These scores correlated positively with
      exercise capacity in patients with IDD or SD. CONCLUSIONS: Impaired HRQOL, in
      both its mental and physical components, is a serious problem for IDD and SD
      patients under treatment. Because exercise intolerance may underlie the reduced
      HRQOL, improving exercise capacity could be an important target for managing
      outpatients with heart failure.

PMID- 18724019
TI  - Gender-related difference in left ventricular diastolic elastance during exercise
      in patients with diabetes mellitus.
AB  - BACKGROUND: Because the ratio of mitral inflow and annular velocity to stroke
      volume has been reported as an index of diastolic elastance (Ed), the hypothesis
      tested in the present study was that Ed during exercise would be more abnormal in
      female than in male patients with type 2 diabetes. METHODS AND RESULTS: Ed was
      measured at rest and during graded supine bicycle exercise (25W, 3-min
      increments) in 53 patients (27 males, mean age 53+/-14 years) with type 2
      diabetes and 53 age- and gender-matched controls. The patients with diabetes were
      divided into 2 groups by gender. Ed was not significantly different at rest
      between men and women, but was significantly higher during exercise in women than
      in men (25 W, 0.15+/-0.04 vs 0.20+/-0.07, p=0.009; 50 W, 0.16+/-0.05 vs 0.21+/
      0.08, p=0.0175). CONCLUSION: Left ventricular (LV) diastolic elastance is
      abnormal during exercise, but not at rest, in patients with diabetes without
      overt heart disease. Female gender was associated with increased LV stiffness
      during exercise among patients with type 2 diabetes.

PMID- 18724020
TI  - Extent of late gadolinium enhancement in cardiovascular magnetic resonance and
      its relation with left ventricular diastolic function in patients with
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: The aim of this study was to determine whether the extent of late
      gadolinium enhancement (LGE) is associated with left ventricular (LV) function in
      patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Forty-seven
      patients with HCM (35 males, mean age 53+/-14, 14 with LV outflow tract
      obstruction) underwent cardiovascular magnetic resonance imaging and
      comprehensive echocardiographic examination. The extent of LGE was expressed as
      LGE volume and LGE percentage of LV volume. LGE was present in 40 (85.1%) of 47
      patients. The mean LGE volume was 36.5+/-36 cm3, and the mean percentage of LV
      volume was 16.4+/-17%. Following adjustment for age, mitral regurgitation and LV
      mass index, LGE volume and percentage positively correlated with the left atrial
      volume index (r=0.388, p=0.009 and r=0.425, p=0.004, respectively). However,
      there was no significant association of functional class, ejection fraction,
      mitral flow, or annular velocities with the extent of LGE. CONCLUSIONS: In HCM
      patients, the extent of LGE positively correlated with the left atrial volume
      index, a surrogate marker of chronic diastolic burden. These findings suggest
      that myocardial scarring may be a pathologic substrate for chronic diastolic
      dysfunction in patients with HCM.

PMID- 18724021
TI  - Main pulmonary arterial distensibility: different presentation between chronic
      pulmonary hypertension and acute pulmonary embolism.
AB  - BACKGROUND: The main pulmonary arterial (PA) distensibility in patients with
      pulmonary hypertension (PH) and pulmonary embolism (PE) is uncertain. METHODS AND
      RESULTS: We enrolled 45 patients with echocardiographic signs of PH and without
      imaging evidence of PE, and another 45 who were found by multidetector-row
      computed tomography to have PE. Fifty normal patients served as a control group.
      The PA distensibility was calculated from the change in main PA diameter between
      diastole and systole, as the maximal systolic diameter minus the minimal
      diastolic diameter divided by the minimal diastolic diameter. The PA
      distensibility is lowest in PH (6.0+/-2.7%), followed by PE (12.9+/-3.4%) and
      then the normal controls (25.9+/-5.7%). Statistical analysis of data obtained
      from patients with PE or PH reveals that a PA distensibility of >8.3% could be
      used to identify PE with a sensitivity of 83% and a specificity of 82%. After a 3
      month anticoagulation, 22 of 45 PE patients had complete resolution of thrombus;
      23 had residual thrombus. The PE patients, regardless of residual thrombus
      presence, had significant improvement of PA distensibility after a 3-month
      anticoagulation, although the diameters of main PA did not shrink. CONCLUSION: PA
      distensibility is a method to distinguish acute PE from chronic PH.

PMID- 18724022
TI  - Prone position is essential for detection of pulmonary vein pseudostenosis by
      enhanced multidetector computed tomography in patients who undergo pulmonary vein
      isolation.
AB  - BACKGROUND: Pulmonary vein (PV) stenosis is a major complication of PV isolation
      (PVI) by catheter ablation, so in the present study the optimal position for
      detecting PV stenosis on enhanced multidetector computed tomography (MDCT) image
      acquisition was determined. METHODS AND RESULTS: The 64-slice enhanced MDCT was
      carried out before and after PVI in 116 consecutive patients with atrial
      fibrillation while they were in the prone position, as well as while supine. The
      supine position MDCT image showed >50% diameter stenosis of the PV in 11 (9%)
      patients before PVI (% diameter stenosis: mean 55+/-4%, range 51-65%). Greater
      than 50% diameter stenosis was seen in the left inferior PV in all 11 patients.
      The prone position attenuated the PV stenosis findings in the MDCT images in all
      11 patients (mean 9+/-6%, range 2-18%). Stenosis visualized on images acquired in
      the supine position was, therefore, concluded to be pseudostenosis caused by
      descending aorta compression. At 3 months after PVI, no significant changes in PV
      diameter were observed in these 11 patients. CONCLUSION: The present study
      demonstrated that the prone position is essential for eliminating PV
      pseudostenosis observed on supine-position enhanced MDCT images. The results also
      indicate that preexisting PV organic stenosis is rare.

PMID- 18724023
TI  - Clinical utility of 3-dimensional echocardiography in the evaluation of tricuspid
      regurgitation caused by pacemaker leads.
AB  - BACKGROUND: This study evaluated the usefulness of 3-dimensional echocardiography
      (3-DE) for identifying permanent pacemaker (PPM) or implantable cardioverter
      defibrillator (ICD) lead-related symptomatic tricuspid regurgitation (TR).
      METHODS AND RESULTS: Eighty-seven patients underwent 3-DE examination: 50
      patients with PPM, 17 with ICD, and 20 with cardiac resynchronization therapy
      devices. TR severity was classified as trivial/mild, moderate, or severe
      according to the ratio of TR area to right atrium area. The 3-DE identified the
      lead route and position at the tricuspid valve in 82 patients (94.2%). In 5
      patients, images without lead-induced artifacts could not be obtained. TR
      severity was trivial/mild in 50 patients, moderate in 20 patients, and severe in
      12 patients. In all patients with trivial/mild TR and all but 1 patient with
      moderate TR, leads were positioned on the annulus side between leaflets. Lead
      induced obstruction to tricuspid valve closing was identified in 1 patient with
      moderate TR and in 7 of 12 patients with severe TR: 4 patients had septal leaflet
      obstruction, and 4 had posterior leaflet obstruction. CONCLUSIONS: The 3-DE can
      identify the lead route and position at the tricuspid valve and lead-related
      severe TR, so may be a useful technique of diagnosing the cause of severe TR in
      patients with PPM or ICD.

PMID- 18724024
TI  - Prediction of therapeutic strategy and outcome for antenatally diagnosed
      pulmonary atresia/stenosis with intact ventricular septum.
AB  - BACKGROUND: The therapeutic strategy for pulmonary atresia (PA) and severe
      pulmonary stenosis (PS) with intact ventricular septum is controversial. Recent
      improvements in prenatal detection necessitate the identification of predictors
      of outcome for appropriate counseling and prenatal management planning. METHODS
      AND RESULTS: Echocardiograms of 18 fetuses antenatally diagnosed with PA (n=14)
      and PS (n=4) were reviewed and the total cardiac dimension (TCD) and tricuspid
      valve diameter (TVD) were measured. The right ventricular end-diastolic volume
      (RVEDV) was calculated from the right ventriculogram of the neonatal period by
      the percentage of the predicted normal value (%RVEDV). There was a positive
      correlation between TVD/TCD and %RVEDV (p<0.001). As the initial treatment,
      balloon atrioseptostomy was performed in 13 cases of TVD/TCD<0.26. As the final
      treatment, patients with TVD/TCD<0.17 underwent or were planned for the Fontan
      procedure. Patients with TVD/TCD>0.21 underwent or were planned for biventricular
      repair. Patients whose TVD/TCD was between 0.17 and 0.21 underwent or were
      planned for 1.5 ventricular repairs. CONCLUSION: TVD/TCD is a useful index for
      selecting the postnatal initial treatment for PA/PS and to predict the final
      status of the fetus. Prenatal detection and prediction of the future status is
      helpful for family counseling. Furthermore, it will help to decide the postnatal
      management prenatally.

PMID- 18724025
TI  - Effect of modified ultrafiltration on postoperative course in neonates with
      complete transposition of the great arteries undergoing arterial switch
      operation.
AB  - BACKGROUND: The purpose of the present study was to evaluate the effect of
      modified ultrafiltration (MUF) on neonates with transposition of the great
      arteries (TGA) undergoing arterial switch operation. METHODS AND RESULTS: The
      current study included 36 neonates who underwent an arterial switch operation
      between 1998 and 2006. Arterio-venous MUF was done in 15 patients (MUF-treated
      group) and the other 21 patients were controls. Parameters included hematocrit,
      hemodynamics, pulmonary function, drain loss, leak of peritoneal fluid, length of
      intubation, and intensive care unit (ICU) stay. The hematocrit increased from
      34+/-2% to 47+/-4% in the MUF-treated group. Blood pressure in the MUF-treated
      group was significantly increased without any change of central venous or left
      atrial pressure. Post-operative oxygenation in the MUF-treated group was greater
      than that of the control group (P/F ratio: 258+/-92 vs 170+/-100 mmHg, p<0.05),
      which did not contribute to decrease in intubation time (54+/-33 vs 52+/-29 h,
      p=NS). Post-operative chest drain loss and peritoneal fluid leak were comparable.
      The ICU stay in the MUF-treated group was significantly shorter than that in the
      controls (101+/-34 vs 139+/-42 h, p<0.05). CONCLUSIONS: MUF brought improvement
      in blood pressure and gas exchange capacity and subsequent shorter ICU stay. MUF
      did not have significant impact on intubation time and capillary leak.

PMID- 18724026
TI  - Metabolic syndrome predicts 10-year mortality in non-diabetic patients following
      coronary artery bypass surgery.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a risk factor for cardiovascular disease
      and mortality, but, the relationship between MetS and survival after coronary
      artery bypass grafting (CABG) remains unclear. METHODS AND RESULTS: The outcomes
      of patients with and without MetS were analyzed. Patients who had undergone CABG
      at Juntendo University Hospital between January 1984 and December 1992 were
      enrolled. The survival search was performed by the end of 2000. The patients were
      categorized by the existence of preoperative MetS using the modified American
      Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI)
      definition with body mass index instead of waist circumference. MetS was present
      in 551 (46.6%) patients and absent in 632 (53.4%). Preoperative MetS was
      associated with long-term poor prognosis in terms of all-cause death (hazard
      ratio (HR) 1.34; 95% confidence interval (CI) 1.03-1.74; p=0.028) and cardiac
      death (HR 2.31; 95% CI 1.36-3.92; p=0.002) in non-diabetic patients. These
      differences in the mortality of the 2 groups were more obvious after 10 years.
      However, among the patients with diabetes, the presence of MetS was not related
      to long-term mortality. CONCLUSIONS: Preoperative MetS predicted increased all
      cause and cardiac mortality, especially after 10 years, in non-diabetic patients
      undergoing CABG.

PMID- 18724027
TI  - Reappraisal of left ventricular to right atrial (LV-RA) shunt in pediatric
      patients with isolated perimembranous ventricular septal defect.
AB  - BACKGROUND: The purpose of this study was to investigate the follow-up results of
      perimembranous ventricular septal defect (VSD) with left ventricular to right
      atrial (LV-RA) shunt since infancy and to analyze the morphologic variations of
      this shunt. METHODS AND RESULTS: The study group comprised 232 consecutive
      pediatric patients with isolated perimembranous VSD and aneurysm, of whom 134
      (58%) had LV-RA shunts. Follow-up echocardiography was performed to assess for
      the size of both the VSD and LV-RA shunt. There were no significant differences
      between groups in terms of sex, age at the initial echocardiography, follow-up
      period, number of patients with tricuspid regurgitation, and initial VSD size.
      There was a significant difference between groups in spontaneous closure
      (p=0.039). The event-free probability (no surgical repair of the defect) was not
      significantly different between the groups (p=0.129). CONCLUSIONS: Perimembranous
      VSD with LV-RA shunt in infancy is common and associated with less chance of
      spontaneous closure. Color Doppler echocardiography can greatly improves the
      diagnostic efficacy and assist in understanding the mechanisms leading to this
      particular anomaly.

PMID- 18724028
TI  - Positive serology for dengue viral infection in pediatric patients with Kawasaki
      disease in southern Thailand.
AB  - BACKGROUND: The etiologic agent of Kawasaki disease (KD) is unknown, but may be
      dengue infection because of reported cases of concomitant KD and dengue. METHODS
      AND RESULTS: Prospective study was conducted to ascertain the relationship of
      positive serology for dengue infection in pediatric patients presenting with KD.
      A total of 65 cases were diagnosed with KD during the period of 4 years and of
      the 48 who had a complete dengue serologic study, 9 had a positive dengue titer.
      CONCLUSION: In the present study 18.7% of patients had proven dengue infection
      from a positive serologic study. Further case-control study with other pediatric
      patients presenting with acute febrile illness needs to be done to support this
      significant finding.

PMID- 18724029
TI  - Changes in the activities of daily living (ADL) in relation to the level of
      amputation of patients undergoing lower extremity amputation for arteriosclerosis
      obliterans (ASO).
AB  - BACKGROUND: The relationship between the level of amputation and the activities
      of daily living (ADL) in Japanese patients with arteriosclerosis obliterans (ASO)
      is unclear. METHODS AND RESULTS: In the present study 81 patients with ASO who
      underwent lower extremity amputation and were discharged from hospital after
      rehabilitation we evaluated. The patients were classified into 4 groups: toe
      amputation group (Toe), heel-preserving amputation group (Heel), below-knee
      amputation group (BK), and above-knee amputation group (AK). ADL at discharge and
      factors affecting the length of hospitalization were determined. Patients were
      walking at discharge in 94.5%, 94.0%, 59.0%, and 0.0% of the Toe, the Heel, BK,
      and AK group, respectively. However, the ratio of patients able to walk
      independently was 68% in the Toe group and 19% in the Heel group. In addition,
      the length of hospital stay was significant shorter in the Toe group than in the
      other groups. Factors affecting the length of hospital stay were the amputation
      level, cerebrovascular disease, reoperation, and diabetes. CONCLUSIONS: ADL are
      less affected and the length of hospital stay is shorter for patients undergoing
      toe amputation than other levels of lower extremity amputation. However, heel
      preserving amputation maintains a comparable level of ADL in terms of ambulatory
      discharge.

PMID- 18724030
TI  - Valuable markers for contrast-induced nephropathy in patients undergoing cardiac
      catheterization.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) frequently complicates cardiac
      catheterization, so the objectives of present study were to investigate the
      usefulness of cystatin C before catheterization and establish a cut-off level for
      CIN, and to examine the changes in cystatin C and several other markers in
      patients with and without CIN. METHODS AND RESULTS: Prospective study of
      consecutive 87 patients who underwent elective catheterization: moderate renal
      disease defined as glomerular filtration rate 30-59 ml . min(-1) .1.73 mm(-2);
      cystatin C and creatinine (Cr), urinary liver-type fatty acid-binding protein (L
      FABP), alpha1, beta2 microglobulins, N-acetyl-beta-D-glucosaminidase, and
      microalbumin were measured immediately before, and 1, 2, and 3 days after
      catheterization. CIN occurred in 18 patients and receiver-operating
      characteristic analysis showed a higher area-under-the-curve for cystatin C
      compared with serum Cr (0.933 vs 0.832 p=0.012). At a cut-off level of >1.2 mg/L,
      cystatin C before catheterization exhibited 94.7% (95% confidence interval: 0.851
      1.015) sensitivity and 84.8% specificity for detecting CIN. Cystatin C levels
      were higher in CIN patients than in those without CIN, even before
      catheterization (cystatin C: 1.08+/-0.22 vs 1.36+/-0.28 mg/L, p=0.007). Urinary L
      FABP was increased on days 1 and 2 in patients with moderate renal disease.
      CONCLUSION: Cystatin C was useful for predicting the occurrence of CIN. Urinary L
      FABP was the only marker of transient renotubular damage.

PMID- 18724031
TI  - Myocardial regulation of p300 and p53 by doxorubicin involves ubiquitin pathways.
AB  - BACKGROUND: Doxorubicin (Dox) depletes p300 from cardiac myocytes and induces
      apoptosis of these cells. p300 protein possesses ubiquitin ligase activity for
      the p53 tumor suppressor gene product, catalyzes p53 polyubiqutination, and
      facilitates p53 degradation in an ubiquitin-dependent manner. The present study
      investigated the ubiquitin-dependent regulation of p53 by Dox and p300 in cardiac
      myocytes. METHODS AND RESULTS: Primary cardiac myocytes from neonatal rats were
      exposed to a proteasome inhibitor, MG132, in culture. MG132 increased both p300
      and p53 protein levels in these cells, suggesting that ubiquitin-dependent
      degradation is involved in the homeostasis of these proteins. Notably, treatment
      of cardiac myocytes with Dox decreased the protein levels of p300 but markedly
      increased those of p53. By immunoprecipitation-Western blotting, it was shown
      that treatment with Dox decreased poly-ubiquitinated p53 but increased that of
      p300 in cardiac myocytes. Finally, the overexpression of p300 in cardiomyocytes
      suppressed the Dox-mediated increase in the p53 level in addition to inhibiting
      Dox-induced apoptosis. CONCLUSION: Dox reciprocally regulates p300 and p53
      through ubiquitin-dependent pathways and that p300, by its ubiquitin ligase
      activity, is partially involved in the ubiquitin-dependent degradation of p53 in
      cardiac myocytes.

PMID- 18724032
TI  - Beneficial effects of exogenous tetrahydrobiopterin on left ventricular
      remodeling after myocardial infarction in rats: the possible role of oxidative
      stress caused by uncoupled endothelial nitric oxide synthase.
AB  - BACKGROUND: Reactive oxygen species (ROS) is deeply involved in the process of
      ventricular remodeling after myocardial infarction (MI). Under oxidative stress,
      endothelial nitric oxide synthase (eNOS) can be converted to a ROS generator,
      because a relative lack of tetrahydrobiopterin (BH4), an essential cofactor for
      NO synthesis, leads to eNOS uncoupling. The uncoupled eNOS generates superoxide
      rather than NO. The possible role of ROS generated by eNOS in ventricular
      remodeling after MI was investigated. METHODS AND RESULTS: Rats were treated with
      oral BH4 supplementation starting at 3 days before coronary artery ligation. At 4
      weeks after MI, there was augmented superoxide production in association with
      reduced BH4/dihydrobiopterin (BH2) ratio and eNOS dimer/monomer protein ratio in
      the heart. Treatment with BH4 increased BH4/BH2 ratio and eNOS dimer/monomer
      ratio, and decreased superoxide production. In BH4-treated MI rats, left
      ventricular size was smaller, thickness of the non-infarcted posterior wall was
      thinner, and cardiac function was preserved compared with the control MI rats.
      CONCLUSIONS: The present study suggested that ventricular remodeling process
      after MI leads to BH4 oxidation and resulted in uncoupled eNOS-derived superoxide
      generation, which further augmented the remodeling process and deteriorated
      cardiac function.

PMID- 18724033
TI  - Biphasic elevation of bilirubin oxidation during myocardial ischemia reperfusion.
AB  - BACKGROUND: The time course of oxidative stress involving nitric oxide (NO) after
      myocardial ischemia reperfusion (MIR) has not been elucidated in detail, so the
      present study was designed to assess the dynamics of oxidative stress after MIR,
      urinary excretion of oxidized bilirubin metabolites (ie, biopyrrins) and their
      generation in various organs. METHODS AND RESULTS: Rat models of MIR were created
      by occluding the left coronary artery for 30 min followed by 48 h of reperfusion.
      Levels of urinary biopyrrins increased biphasically at 8 h and 24 h after MIR.
      Biopyrrins were upregulated in the lungs at 8 h after MIR, according to
      immunohistochemistry and ELISA, and at 24 h biopyrrin expression was increased in
      the heart and lungs. The NO synthase inhibitor, NG-monomethyl-L-arginine,
      significantly diminished biopyrrin synthesis in the heart and lungs at 24 h, but
      not in the lungs at 8 h after MIR. Hemodynamic assessment revealed increased left
      ventricle end-diastolic pressure, suggesting that lung congestion influences
      pulmonary biopyrrin formation. CONCLUSIONS: The dynamics of urinary biopyrrins
      might reflect earlier biopyrrin generation in the lungs and delayed formation in
      both the lungs and heart when NO is involved. Therefore, urinary biopyrrins can
      serve as a useful marker of systemic oxidative stress after MIR.

PMID- 18724034
TI  - Delivery route in bone marrow cell transplantation should be optimized according
      to the etiology of heart disease.
AB  - BACKGROUND: Recent studies have revealed that bone marrow cell (BMC)
      transplantation is effective not only for myocardial infarction (MI), but also
      for dilated cardiomyopathy (DCM). However, the method of administering donor
      cells remains unknown, and may differ between MI and DCM. In the present study,
      intramyocardial (IM) injection and intravenous (IV) delivery of BMC were compared
      in each etiological model. METHODS AND RESULTS: MI was induced in 72 mice and DCM
      in another 36 mice by doxorubicin. BMCs were administered IV or IM in an acute MI
      (AMI), old MI (OMI) or DCM model. In the AMI model, left ventricular (LV)
      remodeling was reduced in both the IM- and IV-groups, but only in the IM-group in
      the OMI model. In the DCM model, the LV dimension of the IV-group was smaller
      than that of the IM-group. Histological examination showed that green fluorescent
      protein (GFP) cells were equally distributed in the infarct area of the IV- and
      IM-groups in AMI, and in the IM-group in the OMI model. In the DCM model, GFP
      cells were diffusely scattered throughout the ventricular wall in the IV-group,
      but were confined to the injection site in the IM-group. CONCLUSIONS: In OMI, IM
      delivery of BMCs was more effective than IV; however, IV delivery was superior in
      DCM. Delivery route should be selected according to the etiology of heart disease
      to optimize the efficacy of BMC transplantation.

PMID- 18724035
TI  - Safety and usefulness of non-occlusion image acquisition technique for optical
      coherence tomography.
AB  - BACKGROUND: Because optical coherence tomography (OCT) requires balloon-occlusion
      to overcome image attenuation by blood, the present study investigated the safety
      and usefulness of a new non-occlusive technique. METHODS AND RESULTS: The 40
      angina patients were assigned to the continuous-flushing method or the balloon
      occlusion method group. The continuous-flushing method was superior for observing
      proximal lesions compared with the balloon-occlusion method (94% vs 55%, p=0.01).
      There were no differences between groups in the visible length and image quality.
      There were no major complications during OCT. CONCLUSIONS: The continuous
      flushing method is safe and useful for OCT.

PMID- 18724036
TI  - Variants in the nestin gene and coronary heart disease.
AB  - BACKGROUND: The intermediate filament protein, nestin, may play a role in tissue
      regeneration and nestin expression has been detected in coronary atherosclerotic
      plaques. To date, no population-based studies concerning the role of the nestin
      gene in coronary heart disease (CHD) have been reported. METHODS AND RESULTS: The
      3 SNPs in the nestin gene were genotyped in 1,494 individuals from 580 Irish
      families. rs11582300 and rs3748570 were associated with early-onset CHD (p=0.04
      and p=0.02). CONCLUSION: Nestin gene variants are associated with early-onset
      CHD. Further research on nestin's role in atherosclerosis is required.

PMID- 18724037
TI  - A case of Takotsubo cardiomyopathy complicated by ventricular septal perforation.
AB  - The patient was a 73-year-old female who developed chest pain and dyspnea 16 days
      after her husband passed away. ST segment elevation was detected on V2-5 by
      electrocardiography and emergency coronary arteriography was done for suspected
      acute myocardial infarction. No coronary arterial stenosis was present and
      ventricular septal perforation and takotsubo cardiomyopathy were diagnosed by
      left ventriculography. The perforation was closed and the patient was discharged
      23 days after surgery. This patient had a very rare case of takotsubo
      cardiomyopathy, which was complicated by ventricular septal perforation and was
      saved by surgical treatment.

PMID- 18724038
TI  - Congenital atresia of unilateral pulmonary veins associated with a single
      ventricle: a rare case report and literature review.
AB  - Congenital atresia or extreme hypoplasia of individual pulmonary veins is a rare
      condition that is usually asymptomatic if it only involves 1 or 2 segments of the
      lungs. It may be fatal if it occurs in combination with other complex cardiac
      defects. The patients often present with recurrent pulmonary infections,
      hemoptysis, or cyanosis in the latter case. A definitive diagnosis can be made by
      cardiac catheterization with selective pulmonary wedge angiography. The treatment
      of this condition is a challenge and is controversial, and the prognosis is
      usually poor. We describe the case of a male infant who suffered from shortness
      of breath and cyanosis since birth. On echocardiography and cardiac
      catheterization, he was found to have a complex congenital heart disease with a
      single ventricle (right ventricle morphology), mitral atresia, large atrial
      septal defect, and atresia of the right pulmonary veins; severe pulmonary
      hypertension was also observed. He underwent pulmonary artery banding at the age
      of 2.5 months, but he died because of a pulmonary infection at the age of 6
      months. In this report, we present this rare case and review the previous
      literature.

PMID- 18724039
TI  - Surgical removal of left ventricular ball-like thrombus following large
      transmural acute myocardial infarction using the infarction exclusion technique:
      David-Komeda procedure.
AB  - A 61-year-old man, who had suffered congestive heart failure following a large
      transmural acute myocardial infarction (AMI) of the anterior wall, developed a
      mobile ball-like thrombus in the left ventricle (LV). On the third day after
      onset of AMI, when the patient had recovered slightly from congestive heart
      failure, we performed coronary artery bypass grafting and LV thrombectomy, then
      the fragile LV wall was successfully repaired using the infarction exclusion
      technique (David-Komeda procedure).

PMID- 18724040
TI  - Recurrent syncope 20 years after mediastinal radiation therapy in a patient with
      breast cancer.
AB  - Mediastinal radiation therapy can cause progressive fibrosis and might, as a
      result, induce various cardiac problems. We encountered a patient who presented
      with recurrent syncope 20 years after radiation therapy for breast cancer. She
      had multiple cardiac problems including bilateral coronary ostial stenoses, pre
      valvular right ventricular outflow tract stenosis, and constrictive pericarditis.
      The cause of syncope was paroxysmal atrioventricular block (an 18-s long pause
      recorded by the implantable loop recorder). The patient was treated by the
      implantation of a pacemaker and did not experience syncope during 9 months of
      follow up.

PMID- 18724041
TI  - Letter by Oda regarding article "relationships between indices of obesity and its
      cardiovascular comorbidities in a Chinese population".

PMID- 18724043
TI  - Hyperleptinemia as a robust risk factor of coronary artery disease and metabolic
      syndrome in type 2 diabetic patients.
AB  - Leptin has been linked to adiposity, insulin resistance, and coronary artery
      disease (CAD). We examined whether the leptin concentrations are associated with
      the risk of CAD and metabolic syndrome (MS). The plasma leptin concentrations
      were measured in 556 diabetic patients (341 men and 215 women). The odds ratio
      (OR) of CAD and MS were increased on moving from the lowest quartile (Q1) of
      leptin concentration to the highest quartile (Q4) and remained significant after
      adjusting for age, sex, BMI, concentrations of total cholesterol, triglyceride,
      or high-sensitivity C-reactive protein (hsCRP), and treatment modalities for
      hyperglycemia. The frequency of CAD was highest in the insulin resistant group
      (Q4 of homeostasis model assessment-insulin resistance index [HOMA-IR]) at Q4 of
      leptin concentration (34.5%), compared with that of Q4 of leptin (26.4%) or HOMA
      IR (21.9%). In multivariate analysis, plasma leptin concentration was identified
      as the most significantly independent predictor for CAD (OR 10.24, 95% CI 3.01 to
      45.05). Other variables with associated with CAD were age, sex, hypertension, low
      HDL cholesterolemia, and hsCRP. In conclusion, hyperleptinemia might be an
      independent risk factor for CAD and MS in diabetic subjects. And the simultaneous
      measurement of insulin resistance and leptin concentration might be helpful for
      screening subjects with a high-risk of CAD.

PMID- 18724044
TI  - Ovarian histological findings in an adult patient with the steroidogenic acute
      regulatory protein (StAR) deficiency reveal the impairment of steroidogenesis by
      lipoid deposition.
AB  - CONTEXT: The steroidogenic acute regulatory protein (StAR) is essential for the
      production of steroid hormones. The mutations in the StAR gene typically cause
      congenital lipoid adrenal hyperplasia (lipoid CAH), characterized by severe
      adrenal insufficiency in both sexes and complete female external genitalia in
      genetic males. Affected 46, XX females feminize at puberty and menstruate but
      have progressive hypergonadotropic hypogonadism. It has been hypothesized that
      the cholesterol accumulation in the steroidogenic cells destroys the residual
      steroidogenic capacity and progressive ovarian failure occurs (two-hit model).
      Additionally, ovulation and luteinization in the patients is supposed to be
      impaired. However, those hypotheses have not been confirmed histologically.
      OBJECTIVE: We examined whether pathological findings of the ovary in a patient of
      lipoid CAH corresponded with two-hit model, and whether ovulation and
      luteinization occurred or not in the patient. SUBJECT: The ovary in an adult 46,
      XX female with a homozygous nonsense mutation (Q258X) in the StAR gene was
      examined. When the patient was age 22 yr, the ovary was resected because of
      enlargement with polycysts and subsequent torsion. RESULT: The affected ovary
      demonstrated remarkable lipoid deposition and changes of the mitochondrial
      ultrastructure. Immunohistochemical examination showed decrease of steroidogenic
      enzymes such as P450 cholesterol side-chain cleavage (P450scc). Additionally, we
      detected corpus albicans in the affected ovary. CONCLUSION: This is the first
      detailed report on ovarian histology in an adult 46, XX female with a null type
      mutation of the StAR gene (Q258X), which indicates the evidence of the impairment
      of ovarian StAR-independent steroidogenesis by lipoid deposition.

PMID- 18724045
TI  - High frequency of AML1/RUNX1 point mutations in radiation-associated
      myelodysplastic syndrome around Semipalatinsk nuclear test site.
AB  - It is known that bone marrow is a sensitive organ to ionizing radiation, and many
      patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) have
      been diagnosed in radiation-treated cases and atomic bomb survivors in Hiroshima
      and Nagasaki. The AML1/RUNX1 gene has been known to be frequently mutated in
      MDS/AML patients among atomic bomb survivors and radiation therapy-related
      MDS/AML patients. In this study, we investigated the AML1 mutations in radiation
      exposed patients with MDS/AML among the residents near the Semipalatinsk Nuclear
      Test Site (SNTS), where the risk of solid cancers and leukemias was increased due
      to the radiation effects. AML1 mutations were identified in 7 (39%) of 18
      radiation-exposed MDS/AML patients. In contrast, no AML1 mutation was found in 13
      unexposed MDS/AML cases. The frequency of AML1 mutations in radiation-exposed
      patients with MDS/AML was significantly higher compared with unexposed patients
      (p < 0.05).We also found a significant correlation between individual estimated
      doses and AML1 mutations (p < 0.05). Considering these results, AML1 point
      mutations might be a useful biomarker that differentiates radio-induced MDS/AML
      from spontaneous MDS/AML.

PMID- 18724046
TI  - Some translations in vascular neurology. The Johann Jacob Wepfer Award 2008.
AB  - 'Translation' in medicine immediately suggests 'translational research', but
      there are many other varieties of 'translation'. I have selected 4 translations
      in the field of vascular neurology in which I have been involved in different
      respects: (1) the translation of results from men to women, taking the example of
      aspirin which, in primary prevention, decreases the risk of myocardial infarction
      in men and the risk of cerebral infarction in women, the reason for this sex
      difference being so far unknown; (2) the 'inverse translational research', from
      bedside to bench, taking the example of the disease we have identified--CADASIL-
      and showing how the study of one patient and his family led to the identification
      of a gene, Notch3, so far unknown in humans and to the discovery of its key role
      in the physiology of vascular smooth muscle cells; (3) the translation from
      individual case reports to multidisciplinary trials taking the example of
      hemicraniectomy in malignant cerebral infarction and emphasizing the interest in
      such rare and severe conditions of pooling and reporting the results of
      randomized clinical trials before the results of individual trials, and (4) the
      translation from research to practice, emphasizing not the well-known 'evidence
      to practice gap' but the slippery slope of 'lack of evidence to overpractice',
      taking the example of patent foramen ovale closure in migraine.

PMID- 18724047
TI  - Report of the 17th European Stroke Conference, Nice, May 13-16, 2008.

PMID- 18724048
TI  - Estrogen receptor alpha gene polymorphisms and stroke.

PMID- 18724049
TI  - Clinical features of mild cognitive impairment differ in the research and
      tertiary clinic settings.
AB  - OBJECTIVE: Comparative analysis of subjects with mild cognitive impairment (MCI)
      diagnosed in a primary research setting and those seen in a tertiary care memory
      disorders clinic. METHODS: Subjects who received a diagnosis of MCI between July
      1, 2005, and December 31, 2006, in a longitudinal research study of normal
      cognition (n = 48) and patients diagnosed in a tertiary care referral clinic (n =
      34) were evaluated using similar methodologies. Comparative analyses of detailed
      medical, neurological and neuropsychological data are presented. RESULTS: The
      diagnosis of MCI was not accepted by 13 of 48 subjects (27%) classified as MCI in
      the primary research setting. Nondegenerative, potentially treatable causes of
      cognitive decline were found in 3 of 34 subjects (9%) seen in the tertiary
      referral clinic and in 11 of 35 subjects (31%) identified as MCI in the primary
      research setting (p = 0.02, Fisher's exact test). MCI subjects identified in the
      primary research setting were older than those referred to the memory clinic
      (mean +/- SD, 79.7 +/- 7.0 vs. 71.5 +/- 9.0 years, p < 0.0001, t test) and had
      more years of education (16.0 +/- 3.2 vs. 13.6 +/- 4.2 years, p < 0.01, t test).
      MCI subjects in the primary research setting appeared to be in a milder stage of
      disease, characterized by higher Mini-Mental State Examination scores (28.2 +/-
      1.8 vs. 25.7 +/- 1.8, p < 0.0001), and a tendency towards single domain
      involvement, predominantly memory (mean number of domains involved, 1.0 vs. 2.5,
      p < 0.0001). More advanced stages of MCI, seen in the tertiary referral
      population, had additional involvement of attention (p < 0.0001, Fisher's exact
      test) and visuospatial domains (p < 0.0002, Fisher's exact test).
      Semiquantitative grading of hippocampal and medial temporal lobe atrophy did not
      differ between groups (p = 0.81, Mann-Whitney U test). CONCLUSIONS: The diagnosis
      of MCI may be unwelcome in naive persons. Remedial causes of MCI should be
      actively investigated. Demographic and clinical characteristics of MCI differ
      between research subjects and patients referred to a tertiary care clinic.

PMID- 18724050
TI  - The genomic basis of disease, mechanisms and assays for genomic disorders.
AB  - In the past fifteen years, an emerging group of genetic diseases have been
      described that result from DNA rearrangements rather than from single nucleotide
      changes. Such conditions have been referred to as genomic disorders. The
      predominant molecular mechanism underlying the rearrangements that cause this
      group of diseases and traits is nonallelic homologous recombination (NAHR)
      (unequal crossing-over between chromatids or chromosomes) utilizing low-copy
      repeats (LCRs) (also known as segmental duplications) as substrates. In
      contradistinction to highly repetitive sequences (e.g. Alu and LINE elements),
      these higher-order genomic architectural features usually span >1kb and up to
      hundreds of kilobases of genomic DNA, share >96% sequence identity and constitute
      >5% of the human genome. Many LCRs have complex structure and have arisen during
      primate speciation as a result of serial segmental duplications. LCRs can
      stimulate and/or mediate constitutional (both recurrent and nonrecurrent),
      evolutionary, and somatic rearrangements. Recently, copy-number variations
      (CNVs), also referred to as large-scale copy-number variations (LCVs) or copy
      number polymorphisms (CNPs), parenthetically often associated with LCRs, have
      been demonstrated as a source of human variation as well as a potential cause of
      diseases. In addition to fluorescence in situ hybridization (FISH), pulsed-field
      gel electrophoresis (PFGE), and in silico analyses, multiplex ligation-dependent
      probe amplification (MLPA), and array comparative genomic hybridization (aCGH)
      with BAC and PAC clones have proven to be useful diagnostic methods for the
      detection and characterization of DNA rearrangements with the latter enabling
      high-resolution genome-wide analysis. The clinical implementation of such
      techniques is revolutionizing clinical cytogenetics.

PMID- 18724051
TI  - Gross deletions and translocations in human genetic disease.
AB  - Translocations and gross deletions constitute an important cause of both cancer
      and inherited disease. Such gene rearrangements are non-randomly distributed in
      the human genome as a consequence of selection for growth advantage and/or the
      inherent potential of some DNA sequences to be frequently involved in breakage
      and recombination. Chromosomal rearrangements are generated by a variety of
      recombinational processes, each characterised by mechanism-specific DNA sequence
      features. Various types of recombinogenic motifs have been shown to promote non
      homologous end joining whilst direct repeats may mediate homologous
      recombination. In addition, repetitive sequence elements can facilitate the
      formation of secondary structure between DNA ends at translocation or gross
      deletion breakpoints, and in so doing, may play a role in illegitimate
      recombination. Although results from DNA breakpoint studies are broadly
      consistent with a role for homologous unequal recombination in deletion
      mutagenesis and a role for non-homologous recombination in the generation of
      translocations, homologous recombination and non-homologous end joining are
      unlikely to be mutually exclusive mechanisms. Thus, chromosomal rearrangements
      will often represent the net result of multiple highly complex molecular
      interactions that are not always readily explicable.

PMID- 18724052
TI  - Nucleotide excision repair and related human diseases.
AB  - Nucleotide excision repair (NER) of DNA-lesions is the most versatile DNA repair
      mechanism involved in genome maintenance, cell and organismal preservation.
      Deciphering the stepwise mechanism of NER has mostly relied on cells from rare
      patients presenting photosensitive, recessively inherited genetic disorders such
      as xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne (CS)
      syndromes. Cells from these patients share various extents of impaired capacity
      of repairing UV-induced DNA lesions (cyclobutane pyrimidine dimers, 6-4
      pyrimidine-pyrimidone photo products) located either in transcribed DNA strands
      or in inactive DNA. We review here the essentials of NER actors and how
      impairment of their activity may lead to distinct and characteristic human
      disorders whose presentation may be limited to developmental trait (TTD; CS), or
      cumulate with cancer susceptibility toward genotoxic aggressions, most notably
      short wavelength ultraviolets.

PMID- 18724053
TI  - Oxidative damage to DNA in non-malignant disease: biomarker or biohazard?
AB  - Oxidative damage to DNA has been examined in many non-malignant conditions, in
      most cases for its utility as a marker of oxidative stress. Whilst this may prove
      useful, attempts to answer the question - why might oxidative damage be important
      in this disease? - would provide added value to the biomarker data, as well as
      give clues to pathogenesis and perhaps therapy. In this chapter, data from the
      scientific literature are considered broadly, where oxidative damage to DNA has
      been analysed either in tissues or in extracellular matrices, such as urine, in
      various groups of non-malignant disease. The lesion of primary focus is 8-hydroxy
      7,8-dihydro-2'-deoxyguanosine, only because this is the most widely measured
      lesion. By coupling biomarker information with the characteristics of the disease
      and a set of general mechanisms whereby DNA oxidation may be pathogenic
      (retrospectively derived from the literature examined), we can ascribe pathogenic
      roles for DNA oxidation in various diseases. Based on available experimental
      evidence, for a wide range of conditions, such mechanisms would include prominent
      roles for the induction of mitochondrial dysfunction, promotion of cytotoxicity
      and modulation of inflammatory responses. Our general conclusion is that,
      dependent on the disease, oxidative DNA damage may be a biomarker, biohazard or
      both of these.

PMID- 18724054
TI  - Dominant non-coding repeat expansions in human disease.
AB  - The general model that dominant diseases are caused by mutations that result in a
      gain or change in function of the corresponding protein was challenged by the
      discovery that the myotonic dystrophy type 1 mutation is a CTG expansion located
      in the 3' untranslated portion of a kinase gene. The subsequent discovery that a
      similar transcribed but untranslated CCTG expansion in an intron causes the same
      multisystemic features in myotonic dystrophy type 2 (DM2), along with other
      developments in the DM1 field, demonstrate a mechanism in which these expansion
      mutations cause disease through a gain of function mechanism triggered by the
      accumulation of transcripts containing CUG or CCUG repeat expansions. A similar
      RNA gain of function mechanism has also been implicated in fragile X tremor
      ataxia syndrome (FXTAS) and may play a role in pathogenesis of other non-coding
      repeat expansion diseases, including spinocerebellar ataxia type 8 (SCA8), SCA10,
      SCA12 and Huntington disease-like 2.

PMID- 18724055
TI  - Telomeres and telomerase in stem cells during aging and disease.
AB  - Cell cycle checkpoints induced by telomere dysfunction represent one of the major
      in vivo tumor suppressor mechanisms preventing cancer but at the same time
      provoking age dependent decline in self-renewal and regeneration of tissues and
      organs. On the other hand, telomere shortening contributes to the initiation of
      cancer by inducing chromosomal instability. Telomere function and telomerase
      activity are mainly associated with actively proliferating cells. Since stem
      cells are continuously proliferating throughout lifetime, it is of great interest
      to explore the role of telomeres and telomerase in stem cells. Although most stem
      cell compartments express telomerase, the level of telomerase activity is not
      sufficient to maintain telomere length of stem cells during aging. Stem cells
      appear to have tighter DNAdamage checkpoint control in comparison to somatic
      cells, which may reflect the need to protect this long lasting cell compartment
      against malignant transformation. These enhanced checkpoint responses may have a
      detrimental impact on stem cell function, by causing increased sensitivity
      towards senescence or apoptosis induced by telomere shortening. This review
      summarizes our knowledge on telomere dynamics and its functional impact on stem
      cells during aging and transformation.

PMID- 18724056
TI  - Retrotransposable elements and human disease.
AB  - Nearly 50% of the human genome is composed of fossils from the remains of past
      transposable element duplication. Mobilization continues in the genomes of extant
      humans but is now restricted to retrotransposons, a class of mobile elements that
      move via a copy and paste mechanism. Currently active retrotransposable elements
      include Long INterspersed Elements (LINEs), Short INterspersed Elements (SINEs)
      and SVA (SINE/VNTR/Alu) elements. Retrotransposons are responsible for creating
      genetic variation and on occasion, disease-causing mutations, within the human
      genome. Approximately 0.27% of all human disease mutations are attributable to
      retrotransposable elements. Different mechanisms of genome alteration created by
      retrotransposable elements include insertional mutagenesis, recombination,
      retrotransposition-mediated and gene conversion-mediated deletion, and 3'
      transduction. Although researchers in the field of human genetics have discovered
      many mutational mechanisms for retrotransposable elements, their contribution to
      genetic variation within humans is still being resolved.

PMID- 18724057
TI  - The spindle checkpoint and chromosomal stability.
AB  - Normal human somatic cells contain 46 chromosomes (22 pairs of autosomes and two
      sex chromosomes). Chromosome missegregation leads to abnormal numbers of
      chromosomes or aneuploidy. This form of genetic instability alters the dosages of
      large subsets of genes, which can result in severe disease phenotypes. Most human
      cancer cells are aneuploid. It is generally believed that aneuploidy contributes
      to cancer formation. The spindle checkpoint is a cell-cycle surveillance
      mechanism that ensures the fidelity of chromosome segregation during mitosis and
      meiosis. In this article, we review our current understanding of the molecular
      basis of the spindle checkpoint and the recent evidence that links the
      malfunction of this checkpoint to aneuploidy and tumorigenesis.

PMID- 18724058
TI  - Protein kinases that regulate chromosome stability and their downstream targets.
AB  - Upon genotoxic stress, checkpoint machinery in eukaryotic cells induces cell
      cycle arrest, thus allowing the cells to repair damaged DNA or stalled
      replication forks. The checkpoint machinery is mediated by phosphorylation
      cascades involving protein kinases and their target proteins. Since the genome is
      under constant threat from DNA damage due to radiation, chemicals and replication
      errors, checkpoint dysregulation can cause catastrophic DNA damage, resulting in
      chromosome instability, aneuploidy, and even tumorigenesis. Two parallel pathways
      that respond to DNA-damage stress have been extensively studied. The first is the
      ATM pathway, which responds to double-stranded DNA breaks, while the second is
      the ATR pathway, which primarily responds to agents that interfere with normal
      DNA replication. The ATM and ATR kinases activate their downstream target
      proteins by phosphorylating specific serine or threonine residues.
      Dephosphorylation by protein phosphatase (PP2A) also participates in the
      regulation of these phosphorylation signals. Of the target proteins, the two
      effector kinases CHK1 and CHK2 are particularly important because they
      phosphorylate additional substrates to maintain chromosome stability after
      various DNA damaging insults. Recent observations indicate that other protein
      kinases that control centrosome duplication and chromosome segregation during the
      cell cycle also play essential roles in maintaining genomic stability.

PMID- 18724059
TI  - The role of the APC tumor suppressor in chromosomal instability.
AB  - Colorectal cancer (CRC) still represents the model of choice to study the
      mechanisms underlying tumor initiation and progression. Accordingly, CRC has been
      central in the analysis of the role played by chromosomal instability (CIN) in
      tumor initiation and progression. Although loss of APC tumor suppressor function
      initiates the adenoma-carcinoma sequence in the vast majority of CRCs through
      constitutive activation of Wnt/beta-catenin signaling, the APC gene also
      represents a candidate CIN gene in CRC. Accordingly, two studies published in
      2001 showed that truncating Apc mutations can lead to both quantitative and
      qualitative ploidy changes in primary mouse cell lines, mainly due to kinetochore
      and centrosome abnormalities. Here, we review and discuss the more recent
      literature on APC's functional activities possibly related to its role in
      eliciting CIN in tumor initiation and progression. We propose a model where loss
      and/or truncation of APC cause mitotic spindle defects that, upon somatic
      inactivation of other putative CIN genes (e.g. spindle and cell cycle checkpoint
      genes, DNA repair, telomere maintenance, etc.) underlie aneuploidy as observed in
      the majority of CRCs.

PMID- 18724060
TI  - c-Myc, Genomic Instability and Disease.
AB  - The proto-oncogene c-myc has been the subject of intensive research since its
      discovery. It is already known that this oncogene targets multiple pathways for
      the initiation and promotion of tumor formation, and that deregulation of this
      protein is observed in numerous cancers. However, despite the plethora of
      information gathered, the exact role and mechanism of action of the protein still
      remains enigmatic. This review focuses on the role of the c-Myc protein in the
      induction of genomic instability and its link with the development of cancer. We
      briefly describe c-Myc protein, its binding partners and downstream targets as
      well as its role in inducing genomic instability and the c-myc-related diseases
      in humans and mice with regard to genomic instability. This review emphasizes the
      notions that c-Myc is a multifunctional protein which also affects the stability
      of the whole genome and triggers the initiation of a complex network of genomic
      instability and therefore acts beyond the characteristics of classical
      transcription factors that only regulate a limited number of downstream targets.
      We propose that c-Myc is a structural modifier of the genome that affects the
      nuclear organization and an important molecule in tumor cell progression through
      the induction of genomic instability.

PMID- 18724061
TI  - Nijmegen breakage syndrome and functions of the responsible protein, NBS1.
AB  - Nijmegen breakage syndrome (NBS) is a rare recessive genetic disorder,
      characterized by bird-like facial appearance, early growth retardation,
      congenital microcephaly, immunodeficiency and high frequency of malignancies. NBS
      belongs to the so-called chromosome instability syndromes; in fact, NBS cells
      display spontaneous chromosomal aberrations and are hypersensitive to DNA double
      strand break-inducing agents, such as ionizing radiations. NBS1, the gene
      underlying the disease, is located on human chromosome 8q21. The disease appears
      to be prevalent in the Eastern and Central European population where more than
      90% of patients are homozygous for the founder mutation 657del5 leading to a
      truncated variant of the protein. NBS1 forms a multimeric complex with
      MRE11/RAD50 nuclease at the C-terminus and retains or recruits them at the
      vicinity of sites of DNA damage by direct binding to histone H2AX, which is
      phosphorylated by PI3-kinase family, such as ATM, in response to DNA damage.
      Thereafter, the NBS1-complex proceeds to rejoin double-strand breaks
      predominantly by homologous recombination repair in vertebrates. NBS cells also
      show to be defective in the activation of intra-S phase checkpoint. We review
      here some cellular and molecular aspects of NBS, which might contribute to the
      clinical symptoms of the disease.

PMID- 18724062
TI  - Werner Syndrome, aging and cancer.
AB  - Werner syndrome (WS) is a rare autosomal recessive genetic instability/cancer
      predisposition disorder that displays many symptoms of premature aging. The
      mimicry of agerelated phenotypes in WS, as well as its dependence on a single
      defective gene product, has provided the impetus for studying this fascinating
      disease as a model system for normative aging and its related pathologies such as
      atherosclerosis, neoplasia, diabetes mellitus, and osteoporosis. The gene product
      defective in WS, WRN, is a member of the RecQ DNA helicase family that is widely
      distributed in all kingdoms of life, and is believed to play a central role in
      genomic stability by preferentially operating on non-canonical DNA structures.
      Although there have been considerable advances in our understanding of the
      biochemistry of WRN and its interacting protein partners, the in vivo molecular
      function(s) of WRN remain(s) elusive. In addition to summarizing the features and
      clinical progression of WS, the following chapter details our current
      understanding of the WRN protein with respect to its biochemistry and its
      interacting protein partners, and considers its putative in vivo roles in various
      DNA transactions.

PMID- 18724063
TI  - Fanconi anemia: causes and consequences of genetic instability.
AB  - Fanconi anemia (FA) is a rare recessive disease that reflects the cellular and
      phenotypic consequences of genetic instability: growth retardation, congenital
      malformations, bone marrow failure, high risk of neoplasia, and premature aging.
      At the cellular level, manifestations of genetic instability include chromosomal
      breakage, cell cycle disturbance, and increased somatic mutation rates. FA cells
      are exquisitely sensitive towards oxygen and alkylating drugs such as mitomycin C
      or diepoxybutane, pointing to a function of FA genes in the defense against
      reactive oxygen species and other DNA damaging agents. FA is caused by biallelic
      mutations in at least 12 different genes which appear to function in the
      maintenance of genomic stability. Eight of the FA proteins form a nuclear core
      complex with a catalytic function involving ubiquitination of the central FANCD2
      protein. The posttranslational modification of FANCD2 promotes its accumulation
      in nuclear foci, together with known DNA maintenance proteins such as BRCA1,
      BRCA2, and the RAD51 recombinase. Biallelic mutations in BRCA2 cause a severe FA
      like phenotype, as do biallelic mutations in FANCD2. In fact, only leaky or
      hypomorphic mutations in this central group of FA genes appear to be compatible
      with life birth and survival. The newly discovered FANCJ (= BRIP1) and FANCM (=
      Hef ) genes correspond to known DNA-maintenance genes (helicase resp. helicase
      associated endonuclease for fork-structured DNA). These genes provide the most
      convincing evidence to date of a direct involvement of FA genes in DNA repair
      functions associated with the resolution of DNA crosslinks and stalled
      replication forks. Even though genetic instability caused by mutational
      inactivation of the FANC genes has detrimental effects for the majority of FA
      patients, around 20% of patients appear to benefit from genetic instability since
      genetic instability also increases the chance of somatic reversion of their
      constitutional mutations. Intragenic crossover, gene conversion, back mutation
      and compensating mutations in cis have all been observed in revertant, and,
      consequently, mosaic FA-patients, leading to improved bone marrow function. There
      probably is no other experiment of nature in our species in which causes and
      consequences of genetic instability, including the role of reactive oxygen
      species, can be better documented and explored than in FA.

PMID- 18724065
TI  - Rab8, a vesicular traffic regulator, is involved in dengue virus infection in
      HepG2 cells.
AB  - OBJECTIVE: The pathogenesis of dengue virus (DV) has not been completely
      clarified. Rab8 regulates vesicular traffic from Golgi to plasma membrane where
      DV is matured and then delivered by exocytosis. In this study, involvement of
      Rab8 in DV serotype 2 (DV2) infection was investigated in HpeG2 cells. METHODS:
      Distributions of Rab8 and DV2, and the number of infection cells were observed by
      immunostaining. HepG2(Rab8AM) and HepG2(Rab8DN) cells were constructed to stably
      express a constitutively active mutant of Rab8 and a dominant negative mutant,
      respectively, which were assessed by flow cytometry. Production of infectious
      virions and the amounts of DV2 entry were detected by standard plaque assay.
      Viral RNA replication was detected by real-time RT-PCR. RESULTS: Rab8 showed high
      co-localization with DV2 in HpeG2 cells and the amount of DV antigen-positive
      cells decreased in HepG2(Rab8AM) and HepG2(Rab8DN) cells. Also, progeny virus
      released from those cells was drastically reduced. Infectious virions produced in
      cells were also significantly reduced, while the viral RNA replication was down
      regulated by a different level. Furthermore, viral entry into those cells was
      reduced by about 80%. CONCLUSIONS: Our data suggest that the function of Rab8 is
      important for DV2 infection, and Rab8 may be involved in DV2 infection.

PMID- 18724064
TI  - Development of human single-chain antibodies against SARS-associated coronavirus.
AB  - The outbreak of severe acute respiratory syndrome (SARS), caused by a distinct
      coronavirus, in 2003 greatly threatened public health in China, Southeast Asia as
      well as North America. Over 1,000 patients died of the SARS virus, representing
      10% of infected people. Like other coronaviruses, the SARS virus also utilizes a
      surface glycoprotein, namely the spike protein, to infect host cells. The spike
      protein of SARS virus consists of 1,255 amino acid residues and can be divided
      into two sub-domains, S1 and S2. The S1 domain mediates the binding of the virus
      to its receptor angiotensin-converting enzyme 2, which is abundantly distributed
      on the surface of human lung cells. The S2 domain mediates membrane fusion
      between the virus and the host cell. Hence two strategies can be used to block
      the infection of the SARS virus, either by interfering with the binding of the S1
      domain to the receptor or by blocking the fusion of the virus with the cell
      membrane mediated by the S2 domain. Several antibodies against the S1 domain have
      been generated and all of them are able to neutralize the virus in vitro and in
      vivo using animal models. Unfortunately, point mutations have been identified in
      the S1 domain, so that the virus isolated in the future may not be recognized by
      these antibodies. As no mutation has been found in the S2 domain indicating that
      this region is more conserved than the S1 domain, it may be a better target for
      antibody binding. After predicting the immunogenicity of the epitopes of the S2
      domain, we chemically synthesized two peptides and also expressed one of them
      using a recombinant DNA method. We screened a phage displaying library of human
      single-chain antibodies (ScFv) against the predicted epitopes and obtained a
      human ScFv which can recognize the SARS virus in vitro.

PMID- 18724066
TI  - Expression and purification of a recombinant adenovirus fiber knob in a
      baculovirus system.
AB  - OBJECTIVES: To construct a recombinant baculovirus expressing the fiber knob
      domain of human adenovirus type 2 modified by the insertion of a foreign peptide,
      purify this protein after its production in insect cells, and to test its
      properties. METHODS: Recombinant baculoviruses expressing the fiber knob were
      produced in Sf9 cells. The recombinant fiber knob was recovered from culture
      supernatants of infected cells and purified by a combination of Ni-NTA and ion
      exchange chromatography. RESULTS: Fiber knob was recovered from the culture media
      as a soluble protein. In the system used, the fiber knob is expressed fused with
      the V5 epitope and a histidine tag, which allowed purification by Ni-NTA
      chromatography. The protein was further purified by ion-exchange chromatography.
      We show that the recombinant fiber knob produced, with 31 extra amino acids in
      the C-terminus, can oligomerize and bind to the adenovirus receptor CAR, as it
      can block the infection of a recombinant type 5 adenovirus. CONCLUSIONS: The
      modified form of the fiber knob, produced in insect cells and purified by Ni-NTA
      and ion-exchange chromatography, retains the properties of oligomerization and
      binding to the fiber natural receptor, CAR. This construct has the potential to
      be a new adjuvant.

PMID- 18724067
TI  - Urinary infections due to multi-drug-resistant Escherichia coli among persons
      with HIV disease at a tertiary AIDS care centre in South India.
AB  - BACKGROUND: While the spectrum of opportunistic infections due to HIV infection
      has been widely discussed, there are very limited data available in south India
      on certain incident infections especially urinary tract infections (UTI) in HIV
      infected subjects. METHODS: Bacterial aetiology of 350 symptomatic UTI in HIV
      infected subjects and the drug resistance pattern of the Escherichia coli
      isolates tested between June 2005 and July 2007 at the YRG Centre for AIDS
      Research and Education, a tertiary HIV Referral Centre in Chennai has been
      described here. RESULTS: E. coli was the most common etiological agent of UTI in
      HIV patients, followed by Staphylococcus aureus, Klebsiella pneumoniae,
      Enterococcus faecalis, Pseudomonas aeruginosa, Proteus spp. and Staphylococcus
      epidermidis. Twenty-nine E. coli isolates were multi-drug-resistant and 83.3% of
      the isolates were resistant to sulfamethoxazole-trimethoprim. CONCLUSIONS:
      Urinary pathogens in HIV-infected patients demonstrate high antimicrobial
      resistance and with majority of therapy for UTIs being empiric, constant updates
      of the aetiological agents and their drug susceptibility pattern would largely be
      beneficial to clinicians in choosing the right drug.

PMID- 18724069
TI  - Macrophage phenotype and renal fibrosis in obstructive nephropathy.
AB  - Macrophages have classically been recognized as key players that may promote
      renal fibrosis. However, several recent studies have suggested a beneficial anti
      fibrotic role of infiltrating macrophages that acts to preserve renal
      architecture in the progressive renal scarring associated with obstructive
      nephropathy. Furthermore, recent investigations indicate a role for macrophages
      in both inflammation and repair during disease processes and this has superseded
      the classical injurious view of macrophages. As a result, the exact role of
      interstitial macrophages upon various facets of renal fibrosis is an important
      challenge that needs to be addressed. In this article, we discuss the possible
      beneficial anti-fibrotic role of infiltrating macrophages in obstructive
      nephropathy and discuss the potential mechanisms that may regulate the effect of
      macrophages upon renal interstitial fibrosis.

PMID- 18724068
TI  - Evidence for persistent vitamin D 1-alpha-hydroxylation in hemodialysis patients:
      evolution of serum 1,25-dihydroxycholecalciferol after 6 months of 25
      hydroxycholecalciferol treatment.
AB  - BACKGROUND: End-stage renal disease (ESRD) patients are thought to have impaired
      1-alpha-hydroxylase capacity, but an extrarenal source of 1,25(OH)(2)D has been
      recognized. OBJECTIVE: The aim of this study was to assess the evolution of serum
      1,25(OH)(2)D in hemodialysis (HD) patients with vitamin D deficiency after 6
      months of 25(OH)D(3) supplementation, and to identify the factors associated with
      persistent 1,25(OH)(2)D production. METHODS: HD patients in a HD center with
      vitamin D deficiency (i.e. 25(OH)D <75 nmol/l) who were not receiving any vitamin
      D derivatives or calcimimetics were studied. Patients who had previously
      undergone parathyroidectomy or nephrectomy or those with uncontrolled
      hypercalcemia or hyperphosphatemia were excluded from this study. The patients
      were administrated a dose of 10-30 microg/day of oral 25(OH)D(3) based on the
      severity of their deficiency. The serum levels of 25(OH)D and 1,25(OH)(2)D
      evolution after 6 months were recorded. Responders were defined as patients with
      an increase in serum 1,25(OH)(2)D levels greater than the median value. Changes
      in mineral metabolism parameters were compared with those in the nonresponders.
      RESULTS: Of the 253 patients, 225 (89%) were vitamin D-deficient, and 43 met the
      inclusion criteria. The patients were 72.6 +/- 10 years old and had been on
      dialysis for 71 +/- 70 months; 39% of the patients were female and 45% were
      diabetics. From baseline to 6 months of treatment, serum 25(OH)D levels increased
      from 27.8 +/- 18 to 118 +/- 34 nmol/l (p < 0.001) and serum 1,25(OH)(2)D levels
      increased from 7.7 +/- 5 to 30.5 +/- 15 pmol/l (p < 0.001) with a median increase
      of 20 pmol/l. The mean serum calcium level increased from 2.19 +/- 0.1 to 2.25 +/
      0.1 mmol/l (p = 0.009), the intact parathyroid hormone (iPTH) level decreased
      from 144 +/- 108 to 108 +/- 63 pg/ml (p = 0.05), and the bone alkaline
      phosphatase (BALP) level remained unchanged. The serum phosphate level increased
      slightly from 1.22 +/- 0.3 to 1.34 +/- 0.2 mmol/l (p = 0.04) with reduced
      hypophosphatemia. Compared with the responders (n = 24), most of the
      nonresponders (n = 19) were diabetic (63 vs. 29%, p = 0.02) and had a lesser
      increase of their 25(OH)D serum level. The serum level of FGF-23 was not
      significant. A positive correlation was observed between serum 1,25(OH)(2)D and
      serum 25(OH)D levels after 6 months of 25(OH)D(3) treatment (p = 0.02).
      CONCLUSION: The Kidney Disease Outcomes Quality Improvement (KDOQI) guidelines do
      not recommend checking and treating vitamin D deficiency in chronic kidney
      disease (CKD) stage 5 patients due to the supposed lack of 1,25(OH)(2)D
      production. These data confirm persistent renal or extra-renal production of
      1,25(OH)(2)D in HD patients after 6 months of 25(OH)D(3) administration. Diabetes
      is the main factor associated with impaired 1,25(OH)(2)D production. 25(OH)D(3
      )administration corrects vitamin D deficiency with few effects on mineral
      metabolism and stability of bone turnover markers.

PMID- 18724070
TI  - Introductory remarks. MolDiag-Paca: an integrated project funded by the European
      Union for Postgenomic Pancreatic Cancer Research.

PMID- 18724072
TI  - Pancreatic ductal adenocarcinoma: cellular origin, signaling pathways and stroma
      contribution.
AB  - Pancreatic cancer has a very poor prognosis, in part due to its diagnosis at late
      stages of the disease and to limited response to chemotherapy and radiotherapy.
      The vast majority of pancreatic cancers are classified as pancreatic ductal
      adenocarcinomas (PDACs). Despite advances in knowledge on the cellular origin of
      PDAC or the involvement of signal transduction pathways therein, many questions
      remain unanswered. In this review, we summarize recent findings and current
      hypotheses regarding these two questions. Since pancreatitis is a risk factor for
      human PDAC, and the latter proceeds with an intense fibrotic reaction, we also
      analyze the role of the stroma in PDAC progression. An improved understanding of
      these key aspects for PDAC ontogeny will open new avenues for tumor prevention,
      early detection, and improved therapy.

PMID- 18724073
TI  - Targeting human mast cells expressing g-protein-coupled receptors in allergic
      diseases.
AB  - The G-protein-coupled receptors (GPCRs) are the largest known group of integral
      membrane receptor proteins and are the most common targets of pharmacotherapy.
      Mast cells (MCs) have been reported to play an important role in allergic
      diseases, such as urticaria and bronchial asthma. There is an increasing body of
      clinical evidence that MCs are recruited into allergic reactions by non-IgE
      dependent mechanisms. Human MCs are activated and secrete histamine in response
      to neuropeptides, such as substance P and somatostatin, mediated by a GPCR,
      MRGX2. The microenvironment surrounding MCs in their resident tissues is likely
      to contain multiple factors that modify antigen-dependent MC activation. MCs
      express various GPCRs, and since the function of human MCs is modulated by
      various GPCR ligands, such as adenosine and sphingosine-1-phosphate, which are
      present in high levels in the bronchial alveolar lavage fluid of asthmatic
      patients, the GPCRs expressed on MCs may play an important role in human allergic
      diseases. The GPCRs expressed on MCs may serve as drug targets for the treatment
      of allergic diseases.

PMID- 18724099
TI  - Sentinel lymph node biopsy for patients with diagnostically controversial
      Spitzoid melanocytic tumors?
AB  - The distinction of a Spitz nevus from melanoma can be very difficult.
      Pathologists may disagree on whether a Spitzoid melanocytic proliferation is
      benign or malignant, or acknowledge uncertainty about the diagnosis. As long as
      melanoma is suspected or strongly considered, a clinical management plan is often
      adopted as if the patient had melanoma, which may include sentinel lymph node
      (SLN) biopsy for staging. The findings of the sentinel node may resolve the
      diagnostic controversy about the primary tumor, but there is also the risk for
      more diagnostic confusion, uncertainty, and errors. We review the arguments in
      favor and against SLN biopsy for patients with diagnostically controversial
      Spitzoid melanocytic tumors, summarize current experience, and illustrate
      diagnostic pitfalls. Although SLN biopsy provides prognostic information helpful
      for clinical trials, we caution against performing the procedure as a diagnostic
      adjunct.

PMID- 18724074
TI  - Anti-IgE antibody therapy for Japanese cedar pollinosis: omalizumab update.
AB  - Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollens is a
      substantial problem in Japan. Omalizumab, a novel humanized monoclonal anti
      immunoglobulin E (IgE) antibody, has already been proven to reduce symptoms
      associated with SAR. To investigate the safety and efficacy of omalizumab in the
      treatment of patients with Japanese cedar pollen-induced SAR compared to placebo
      or anti-allergic drug, two randomized, double-blind studies were conducted in
      Japan. Omalizumab (150, 225, 300, or 375 mg) or placebo was administered
      subcutaneously every 2 or 4 weeks based on serum total IgE and body weight at
      baseline. IPD was administered 300 mg per day through the season. Primary and all
      secondary efficacy variable scores were significantly lower in the omalizumab
      group than in the placebo group (P < .01) and IPD, Th2 cytokine inhibitor group
      (P < .01). Omalizumab was effective and safe in the treatment of SAR induced by
      Japanese cedar pollens. And the methods of increasing effects by combining
      omalizumab with antibody-specific immunotherapy are being considered. These
      strategy is more effective than immune-therapy alone.

PMID- 18724100
TI  - Diagnostic problems in anal pathology.
AB  - Anal squamous cell carcinoma and its precursor lesions are increasing in
      incidence in the United States and Europe. This trend predates human
      immunodeficiency virus/acquired immune deficiency syndrome and has been
      associated with persistent high-risk human papilloma virus (HPV) genotype
      infection, previous lower genital tract dysplasia/carcinoma, high frequency
      anoreceptive intercourse, heavy cigarette smoking, immunosuppression in solid
      organ transplant and immune disorders, and human immunodeficiency virus
      seropositivity. Screening protocols for at-risk patients are under active
      investigation and pathologists are often asked to assess anal canal and perianal
      biopsies for the presence of dysplasia and/or invasive carcinoma. Because
      underdiagnosis and overdiagnosis of anal cancer and precancer may lead to
      inappropriate treatment, it is important for the pathologist to be aware of
      current screening strategies, specific risk lesions, and the role of pathology in
      initial diagnosis and evaluation of anal biopsy and/or resection specimens.
      Standardized histologic criteria and uniform terminology should be used for
      reporting all anal canal and perianal squamous intraepithelial lesions. HPV
      subtyping, anal cytology, and recently identified biomarkers, such as p16 and
      Becton Dickinson ProEx C may provide additional information in problematic cases,
      but it is important to be aware of the limitations of these assays. HPV has been
      linked to all the major histologic subtypes of anal carcinoma (eg, basaloid,
      cloacogenic, transitional, etc.) and this association is strongest for anal canal
      lesions. With the possible exception of the microcystic pattern, histologic
      subtype does not seem to predict prognosis; and anal squamous cell carcinomas
      should be classified as either keratinizing or nonkeratinizing. Poorly
      differentiated squamous cell carcinomas have a worse prognosis and should be
      distinguished from poorly differentiated adenocarcinoma, melanoma, and
      neuroendocrine tumors. Very well differentiated squamous cell carcinoma with
      pushing margins (so-called giant condyloma of Buschke and Lowenstein) should be
      classified as verrucous carcinoma; this tumor shows aggressive local infiltration
      but does not metastasize. As all anal condylomata may harbor foci of high-grade
      dysplasia or invasive carcinoma, careful sectioning and complete histologic
      examination is required.

PMID- 18724101
TI  - Bladder cancer detection using FISH (UroVysion assay).
AB  - UroVysion is a fluorescence in situ hybridization assay that was developed for
      the detection of bladder cancer in urine specimens. It consists of fluorescently
      labeled DNA probes to the pericentromeric regions of chromosomes 3 (red), 7
      (green), and 17 (aqua) and to the 9p21 band (gold) location of the P16 tumor
      suppressor gene. The UroVysion assay works by detecting urinary cells that have
      chromosomal abnormalities consistent with a diagnosis of bladder cancer. Studies
      have shown that UroVysion is more sensitive than urine cytology for the detection
      of all stages and grades of bladder cancer. UroVysion is Food and Drug
      Administration-approved for the detection of recurrent bladder cancer in voided
      urine specimens from patients with a history of bladder cancer and for the
      detection of bladder cancer in voided urine specimens from patients with gross or
      microscopic hematuria, but no previous history of bladder cancer. Recent studies
      also suggest that UroVysion may be useful for assessing superficial bladder
      cancer patients' response to bacillus Calmette-Guerin therapy and in detecting
      upper tract urothelial carcinoma.

PMID- 18724102
TI  - Gray zones in brain tumor classification: evolving concepts.
AB  - The World Health Organization recently updated its classification of central
      nervous system tumors, adding 8 entities, as well as defining new variants and
      morphologic patterns of existing entities. Despite the continued refinement of
      brain tumor histologic classification and grading, there remain some diagnostic
      "gray zones" that challenge general surgical pathologists and neuropathologists
      alike. These include the presence of oligodendroglial features in (mixed)
      oligoastrocytomas and glioblastomas (GBMs), GBM variants (such as small cell
      GBM), meningioma classification and grading, medulloblastoma variants, ependymoma
      grading, the presence of "neuronal features" in otherwise morphologically classic
      gliomas, and low-grade gliomas with high Ki-67 labeling indices. In the current
      review, we discuss these issues and offer some practical guidelines for dealing
      with problematic cases.

PMID- 18724071
TI  - Biological approaches to therapy of pancreatic cancer.
AB  - Pancreatic cancer is a lethal disease and notoriously difficult to treat. Only a
      small proportion is curative by surgical resection, whilst standard chemotherapy
      for patients with advanced disease has only modest effect with substantial
      toxicity. Clearly there is a need for the continual development of novel
      therapeutic agents to improve the current situation. Improvement of our
      understanding of the disease has generated a large number of studies on
      biological approaches targeting the molecular abnormalities of pancreatic cancer,
      including gene therapy and signal transduction inhibition, antiangiogenic and
      matrix metalloproteinase inhibition, oncolytic viral therapy and immunotherapy.
      This article provides a review of these approaches, both investigated in the
      laboratories and in subsequent clinical trials.

PMID- 18724108
TI  - Healing and restoration.

PMID- 18724110
TI  - The unitary life pattern of persons experiencing serenity in recovery from
      alcohol and drug addiction.
AB  - People recovering from addiction to alcohol or drugs often acknowledge the need
      for complete change in life pattern orientation in a journey toward healing.
      Serenity is the hallmark of recovery according to the tenets of 12-step programs,
      but little is known about the actual experience of serenity in healing from
      addiction. From a perspective of unitary pattern appreciation and a method of
      unitary appreciative inquiry, this study explored the experience of serenity
      among 9 people recovering from alcohol and/or drug addiction. Results are
      portrayed in both individual and group profiles, depicted in a format that
      integrates empirical findings as poetry.

PMID- 18724109
TI  - Nurturing natural resources: the ecology of interpersonal relationships in women
      who have thrived despite childhood maltreatment.
AB  - Childhood maltreatment and its consequences are a public health issue. There
      continues to be a need for improving the lives and life prospects for survivors
      of child abuse. The important role that positive interactions can play was
      evident in a large study of women who considered themselves successful despite
      maltreatment. Interactions of import ranged from brief encounters with strangers
      to enduring relationships. Two distinct motifs emerged: The "Saw something in me"
      and "No matter what" relationships. Findings will be discussed within the context
      of extant theories with possible implications for researchers, practitioners, and
      careful, caring adults in any setting.

PMID- 18724111
TI  - Healing after disasters in early-20th-century Texas.
AB  - This historical study analyzes 2 disasters in Texas in the early 20th century:
      the 1937 school explosion in New London and the 1947 Texas City ship explosion.
      Disaster narratives and commemoration activities are examined as means of healing
      and restoration after a catastrophic event. Specifically, this article discusses
      contextual factors of time and place, Coastal and East Texas between 1937 and
      1947, and shows how these factors shaped the ways in which people made sense of
      their disaster experiences. This included not only the influence of geography but
      also economics, social position, racial characterizations, and religious beliefs.
      The article also considers conflicting and biased factors that can occur
      regarding time and place and how these factors influenced narrative
      constructions.

PMID- 18724112
TI  - Reexploring the subconcepts of the Wittmann-Price Theory Of Emancipated Decision
      Making in women's healthcare.
AB  - This study explored the 5 subconcepts (empowerment, flexible environment,
      personal knowledge, reflection, and social norms) of the Wittmann-Price Theory of
      Emancipated Decision Making (EDM) in women's healthcare, a theoretical model.
      Pain management for labor was the clinical exemplar. The correlation of EDM and
      satisfaction with the decision (SWD) was measured, and flexible environment was
      the subscale with the highest mean score. There was a significant relationship
      between EDM and SWD (r = 0.70, P < .001). Personal knowledge and flexible
      environment were the best predictors of satisfaction. This study advances the
      theory of EDM for the nursing care of women.

PMID- 18724113
TI  - The battle between hoping and suffering: a conceptual model of hope within a
      context of spinal cord injury.
AB  - The aim of this longitudinal study was to explore 10 patients' experiences of the
      meaning they attribute to the substance of hope and the process of hoping during
      the first 3 to 4 years following a spinal cord injury. This qualitative study is
      a synthesis of three empirical studies of hope and the overall aim was to deepen
      the understanding of the phenomenon of hope, based on the text representing the
      main contextual findings, to develop a theoretical framework on hope within a
      context of spinal cord injury, illustrated in the conceptual model. In
      correspondence with Ricoeur, this conceptual model, which was developed from a
      new understanding, based on a new text of the phenomenon of hope, develops a new
      and deeper understanding of the meaning of hope. Findings revealed 9 themes:
      universal hope, uncertain hope, hope as a turning point, the power of hope,
      boundless creative and flexible hope, enduring hope, despairing hope, body
      related hope, and existential hope. The conceptual model was derived from these
      themes, illustrated as The Battle between Hoping and Suffering and The Road of
      Hope. The interpretations also revealed a distinction between being in hope and
      having hope, and having a hope of improvements was the main focus at the early
      stage of rehabilitation, whereas being in hope as being just fine was the main
      focus after 3 to 4 years of rehabilitation.

PMID- 18724114
TI  - An essay on women, despair, and healing: a personal narrative.
AB  - Much of my career has focused on knowing and understanding human wholeness,
      developing praxis approaches for life patterning and healing, and inquiring into
      the lives of the women who have been abused as children and live with despair.
      Sensing the desire of people to share their stories to understand their despair
      and being discontented with fragmenting and dehumanizing approaches to practice
      and research, I sought an alternative path. This article describes the personal
      and professional journey that led me into the lives of women, the discoveries and
      revelations that emerged, and an appreciation of unimagined potentials for
      healing. It also confirmed the need for nursing to examine its underlying
      assumptions of healing.

PMID- 18724115
TI  - Home as place for healing.
AB  - Although environment is a core concept in nursing, it has had little theoretical
      or empirical attention, especially related to healing. This article explores the
      following aspects of the meaning of healing as they relate to environment as
      place: (a) healing is grounded in suffering; (b) healing is active and requires
      presence of the patient and the nurse; and (c) healing is private, spiritual, and
      profound. Home is explored as a place for healing. The article explores
      implications for the study of meaning of home, when home is not a place for
      healing, and future directions for theory and research.

PMID- 18724116
TI  - Photo stories, Ricoeur, and experiences from practice: a hermeneutic dialogue.
AB  - The purpose of this article is to demonstrate how a particular narrative approach
      in nursing, namely the photo instrument can be connected with Ricoeur's
      hermeneutic philosophy. Ricoeur's concept of mimesis, when supplemented with the
      concept of performance, is shown relevant for understanding how patients
      construct and reformulate meaning in illness experiences. A single-case study is
      presented for a tentative exploration of how the key concepts of mimesis and
      performance can broaden our understanding of practice. More specifically it
      concerned the use of photographs in a group with psychiatric patients.

PMID- 18724118
TI  - The importance of preoperative hemoglobin evaluation in large volume liposuction:
      lessons learned from our 15-year experience.
AB  - Liposuction of >5 L of total aspirate at one setting is defined as large volume
      liposuction (LVL). A retrospective chart review was performed on all patients who
      underwent LVL from January 1990 to June 2005. Sixty-two patients underwent LVL.
      The mean volume of total aspirate was 8 L (5.0-11.7 L). There were a total of 6
      patients who had complications. These included symptomatic postoperative anemia
      requiring blood transfusions on postoperative day 1 (n = 5), and an expanding
      hematoma requiring operative evacuation without transfusion (n = 1). Two of the
      patients who had blood transfusions had a history of gastric bypass and all of
      the patients were preoperatively anemic (<11.5 mg/dL). The mean follow up was 38
      months. LVL is safe when performed in healthy patients under strict guidelines.
      Hemoglobin levels of all potential LVL patients should be checked preoperatively,
      and surgery should be withheld for levels <12 g/dL.

PMID- 18724119
TI  - The effect of weight loss surgery and body mass index on wound complications
      after abdominal contouring operations.
AB  - Abdominal contouring operations are in high demand after massive weight loss.
      Anecdotally, wound problems seemed to occur frequently in this patient
      population. Our study was designed to delineate risk factors for wound
      complications after body contouring. Our retrospective institutional analysis was
      assembled from 222 patients between 2001 and 2006 who underwent either
      abdominoplasty (N = 89) or panniculectomy (N = 133). Weight loss surgery (WLS)
      before body contouring occurred in 63% of our patients. Overall the wound
      complication rate in these patients was 34%: healing-disturbance 11%, wound
      infection 12%, hematoma 6%, and seroma 14%. WLS patients had an increase in wound
      complications overall (41% vs. 22%; P < 0.01) and in all categories of wound
      complications compared with non-WLS-patients by univariate methods of analysis.
      In a multivariate regression model, only American Society of Anesthesiologists
      Physical Status Classification was a significant independent risk factor for
      wound complications. In conclusion, WLS patients are at increased risk for wound
      complications and American Society of Anesthesiologists Physical Status
      Classification is the most predictive of risk.

PMID- 18724120
TI  - Breast augmentation under general anesthesia versus monitored anesthesia care: a
      retrospective comparative study.
AB  - Breast augmentation is one of the leading esthetic surgeries, enjoying high
      satisfaction rates. Pain, nausea, and vomiting are frequent shortcomings of the
      immediate postoperative period. The aim of this study was to compare breast
      augmentation from the anesthetic point of view: general anesthesia (GA) versus
      monitored anesthesia care (MAC). The charts of 115 patients were reviewed in this
      retrospective study performed over a period of 2 years. Sixty-nine women chose to
      have the surgery done under MAC, and 46 under GA. Statistically significant
      differences were noted in both postoperative hospital stay (16.1 +/- 6.78 hours
      vs. 11.7 +/- 6.10 hours) and frequency of vomiting (mean, 0.5 vs. 0.22 times per
      patient) after GA and MAC, respectively (Mann-Whitney, P < 0.01). Postoperative
      pain, assessed using the visual analog scale, was significantly higher (mean
      visual analog scale, 5 vs. 3.27) when the prosthesis was placed in the
      submuscular plane compared with the subglandular plane (Mann-Whitney, P = 0.043).
      When offered a choice, more women preferred MAC over GA for their breast
      augmentation procedure. Less vomiting and shorter postoperative hospitalization
      were prominent in the MAC group.

PMID- 18724121
TI  - Upper cervicothoracic sympathetic block increases blood supply of unipedicled
      TRAM flap.
AB  - A prospective clinical study was conducted to evaluate the impact of upper
      cervicothoracic sympathetic block (CTGB) on blood supply of the unipedicled
      transverse rectus abdominis musculocutaneous (TRAM) flap. The use of the
      technique is first reported herein, as a manipulation improving arterial blood
      flow within the flap in high-risk patients, thus reducing postoperative
      morbidity. From March 2003 to September 2006, 28 heavy smokers, who underwent
      delayed breast reconstruction with unipedicled TRAM flap, were included in the
      study. Intraoperative upper cervicothoracic block (ganglia C5,6,7 and T1,2) was
      performed in 16 patients (group A), while 12 patients, who did not consent to
      have the blockade (group B), were the control. Clinical evaluation and
      thermographic monitoring of skin temperature, using the Thermacam A40 (FLIR
      systems, Wilsonville, OR), was used in all patients and determined the blood flow
      within the flap. All patients were monitored for early and late complications. In
      all group A patients, CTGB resulted in TRAM flap temperature increase within 9.5
      to 16 min. Flap temperature elevation was found to be significantly higher (P <
      0.001) and hospital stay was significantly shorter (P = 0.004) in group A
      patients. No CTGB or TRAM flap complications were recorded in group A patients.
      However, in group B, major fat necrosis occurred in 2 patients and partial (1/3)
      flap necrosis in 1 patient. Upper cervicothoracic sympathetic block is a
      reliable, safe, and useful technique for increasing blood flow within TRAM flaps
      in high-risk patients, like heavy smokers, and it minimizes postoperative
      morbidity.

PMID- 18724122
TI  - Intrapleural bupivicaine in latissimus dorsi breast reconstruction.
AB  - The use of intrapleural (IP) analgesia for controlling post-operative pain in
      breast reconstruction is not well documented. The objective of this study was to
      assess the value of IP bupivacaine in those patients undergoing latissimus dorsi
      breast reconstruction. Twenty-six patients received a single bupivacaine IP
      injection at induction of anesthesia. Eighteen of these patients also received a
      24-hour postoperative IP infusion. A control group of 22 patients did not receive
      an IP block. All patients had access to morphine via patient-controlled analgesia
      pumps. The 24-hour morphine requirements were recorded for each group and the
      data were analyzed by Student t test. Significance was taken at the 5% level. The
      mean morphine requirement in the control group was 39.2 mg +/- 2.89 mg. This was
      significantly greater than the requirement of the 8 patients who had a single IP
      injection of bupivacaine at induction (10.1 mg +/- 2.76 mg), P < 0.001. It was
      also significantly greater than that of the 18 patients who received an IP
      infusion (2.7 mg +/- 1.35 mg), P < 0.0001. The infusion group required
      significantly less morphine than the single injection group did, P < 0.02. No
      complications following IP injection were noted in this series. Intrapleural
      analgesia is a safe technique and significantly reduces the requirement for
      postoperative opiate analgesia in those undergoing latissimus dorsi breast
      reconstruction.

PMID- 18724123
TI  - Skin sparing nipple reconstruction with polytetrafluoroethylene implant.
AB  - This paper describes a technique in which implanted polytetrafluoroethylene is
      used to reconstruct the nipple without having to perform a local flap or graft
      from a distant site. This procedure offers the advantage of not taking skin to
      reconstruct the nipple. In addition, the projection of the nipple is provided by
      the implanted material and is not obligated to blood supplying a local tissue
      flap. For these reasons, this technique offers an attractive alternative for
      patients who have failed past techniques or have compromised vascular supply due
      to radiation therapy.

PMID- 18724125
TI  - Microsurgical scalp reconstruction after a mountain lion attack.
AB  - Mountain lion attacks on humans are rare and potentially fatal. Although few
      victims experience minor injuries, permanent disfigurement and disability is
      common among survivors of these assaults. Since 1986, a steady number of mountain
      lion attacks have been noted in California. We report a recent attack of a cougar
      on a couple hiking in California's Prairie Creek Redwoods State Park. The victim
      sustained a significant scalp injury that led to a life-threatening soft-tissue
      infection. We present an analysis of the injury pattern as it relates to the bite
      marks, the resulting degloving injury, and the surgical reconstruction. We also
      offer a current survey of the pathogens often found in cats' and mountain lions'
      bite wounds and the appropriate antibiotic treatment. Given the infrequency at
      which clinicians encounter mountain lion injuries, we recommend that after
      initial management and exclusion of life threatening injuries patients be
      transferred to a tertiary care facility capable of managing the various
      reconstructive challenges such as the one presented in this case.

PMID- 18724124
TI  - High-resolution ultrasound in the diagnosis of upper limb disorders: a tertiary
      referral centre experience.
AB  - The purpose of this study is to determine the reliability of high-resolution
      ultrasound (HRUS) in the diagnosis of upper limb disorders compared with the
      initial clinical opinion. We prospectively studied 178 patients referred for HRUS
      examination (47.2% hand, 34.8% wrist, and 18% elbow examinations) by recording
      the clinical opinion, the specific ultrasound diagnosis, and the final diagnosis,
      as established by surgery (79.9%) or follow-up (20.1%). HRUS examination was
      highly reliable in diagnosing cystic lesions, synovial disease, ligament injury
      and foreign bodies (100%), and slightly less reliable for solid lesions (82.1%)
      and nerve, bone, and tendon disorders (97%, 91.7%, 86.5%, respectively). HRUS
      examination resulted in significantly more correct diagnoses (92.1%) than the
      clinical opinion (70.8%) (McNemar test, P = 0.001). The agreement between the
      HRUS diagnosis and the clinical opinion was slight (Kappa test, k = 0.16). HRUS
      examination is more reliable than clinical examination in diagnosing upper limb
      disorders.

PMID- 18724126
TI  - Chronic postburn palmar contractures reconstruction using the medial pedis
      perforator flap.
AB  - Chronic flexion contractures of the palm of the hand impair hand function
      considerably and cause a poor esthetic appearance. Various reconstructive methods
      have been used for the treatment. However, satisfactory esthetic and functional
      results are difficult to achieve due to the unique anatomic characteristics of
      the palmar region, such as thick, cornified, stratified squamous epithelium. In
      the present study, free medialis pedis flap was used in a number of patients who
      suffered from severe palmar flexion contractures due to burn injuries. Here, the
      experience, technique, and follow-up results are presented. Eleven patients
      admitting to our department with palmar flexion contracture were reconstructed
      with free medialis pedis flap from 2004 to 2007. All were men and ranged in age
      from 19 to 22 years old (average, 21 years). In all cases, different parts of
      palmar region were covered. In all cases except 2, arterial anastomosis was done
      to proper digital arteries. Although the concomitant vein and superficial vein
      were prepared in all cases, only superficial vein of flap was used for
      anastomosis. In one case, the donor site was closed primarily, the others were
      closed with skin graft. The transplanted flaps survived with satisfactory
      recovery in function and appearance. In 2 cases, transient venous insufficiency
      was observed and resulted in possible increase in flap thickness. Grasp function
      of the hand was dramatically improved. The follow-up period ranged from 10 to 22
      months. In one case, the flap required debulking. Postoperative follow-up
      revealed no marked donor site morbidity. We determined that the medialis pedis
      flap was a remarkable alternative for palmar reconstruction of the hand and
      digits due to burn because of its glabrous skin, which was very similar to palmar
      skin, and low donor site morbidity.

PMID- 18724127
TI  - Medial sural artery perforator flap for intraoral reconstruction following cancer
      ablation.
AB  - In oral cavity reconstruction, the fasciocutaneous flaps of the distal
      extremities have always been preferred to any other kind of flap because of their
      thinness and pliability, which makes them adaptable to different areas in the
      oral cavity. The radial forearm flap is frequently considered the first choice
      for intraoral reconstruction, but the disadvantages of donor site morbidity
      include sacrificing a major artery to the hand and leaving a conspicuous donor
      site scar. The search for another primarily thinned skin flap as an alternative
      has led to the application of the medial sural artery perforator flap, which is
      harvested from the medial aspect of the upper calf. Between June 2003 and March
      2007, 22 free medial sural artery perforator flaps were transferred for intraoral
      defects after cancer ablation, including tongue and floor of mouth (15 cases),
      buccal mucosa (5 cases), retromolar trigone (1 case), and anterior floor of mouth
      (1 case). We paid attention to the major perforator (vein > or =1 mm), which was
      confirmed by the endoscope, as the vascular relay for the skin flap. The size of
      the skin paddle varied from 7.5 x 4 cm to 17 x 8 cm. The main advantage of this
      flap is that it provides thin and pliable coverage to achieve better accuracy in
      the oral cavity. Other advantages of minimizing donor site morbidity include
      maintaining the function of the medial gastrocnemius muscle, avoiding the need to
      sacrifice major arteries of the leg, and possible primary closure of the donor
      defect.

PMID- 18724128
TI  - A survey of microvascular protocols for lower extremity free tissue transfer II:
      postoperative care.
AB  - Due to the complex, and often tenuous nature of microsurgical tissue transfer,
      postoperative monitoring of free tissue flaps plays a vital role in the
      management of such patients. Some of the more challenging reconstructive problems
      occur in patients with lower extremity trauma, yet to date, no preferred protocol
      exists for the postoperative care of lower extremity free flaps. The present
      study sought to evaluate and assess current preferences in monitoring following
      lower extremity free tissue transfer. Members of the American Society of Plastic
      Surgeons (ASPS) were surveyed with regard to their choice for postoperative
      monitoring and return to dependent positioning ("dangling"). The results
      demonstrate that there is some agreement among surgeons regarding the optimal
      means for postoperative monitoring. Most rely on clinical observation in addition
      to conventional Doppler probe for an average of 4.8 days. Most surgeons follow
      their own flaps in addition to relying on the residents and nursing staff. The
      study also notes a wide variety in the times and frequencies at which dangling of
      the extremity was commenced. Most respondents initiate dangling within 2 weeks of
      surgery and begin with only 1 to 5 minutes per session.

PMID- 18724129
TI  - The value of the maxillo-malar osteotomy in the treatment of Crouzon syndrome
      with exorbitism.
AB  - Premature fusion of the cranial sutures along with midface hypoplasia, shallow
      orbits, and ocular proptosis are the principal features of Crouzon syndrome.
      Treatment varies according to the variable expressivity of the disease and
      usually begins during a child's first year with fronto-orbital advancement with
      cranial decompression. Subsequent development of midfacial hypoplasia needs
      correction. Procedures for this purpose include the Le Fort III osteotomy or its
      segmental variants, monobloc frontofacial advancement, or bipartition osteotomy.
      Adult Crouzon often presents with marked midface hypoplasia and exorbitism. We
      report an adult-diagnosed Crouzon syndrome case with typical facial features and
      exorbitism corrected by orbital decompression and zygomaticomaxillary
      advancement.

PMID- 18724130
TI  - Craniosynostotic variations in syndromic, identical twins.
AB  - Despite intense research, etiologies underlying syndromic craniosynostosis remain
      poorly understood. While syndrome-related genetic factors have garnered much
      attention, external forces likely play a large role as well. In contrast to well
      defined genetic abnormalities that may be precisely identified and statistically
      quantified, characterization of more environmental factors has proven difficult.
      Much of this challenge stems from difficulty in isolating genetic components.
      However, in the event that 2 individuals share similar genetics, a clearer
      picture of external factors impacting phenotypic differences may be drawn.
      Because monozygotic discordant twins have identical genomes, the differences
      between affected and unaffected members are the result of the environment. Here,
      we discuss identical twin females who presented with Crouzon syndrome, as well as
      variations in craniosynostosis. In addition to highlighting the impact of
      nongenetic factors on craniosynostosis phenotype, we review several environmental
      elements that may have played a role in this unusual case.

PMID- 18724131
TI  - Risk analysis of deep sternal wound infections and their impact on long-term
      survival: a propensity analysis.
AB  - The objectives of this study are to determine risk factors associated with deep
      sternal wound infections (DSWIs) following cardiac surgery, and to describe their
      impact on long-term survival. Data was obtained from a departmental database.
      Analysis included 7,978 consecutive patients who underwent cardiac surgery
      between 1997 and 2003. To identify risk factors for DSWI, regression analysis was
      performed. The probability scores obtained from logistic regression were used for
      propensity analysis of 2 groups. Kaplan-Meier analysis with log-rank test and Cox
      proportional hazard models were then used in survival analysis. DSWI developed in
      123 of 7,978 patients (1.5%). Preoperative predictors of DSWI were body mass
      index >30 kg/m(2) (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1 to
      2.4; P < 0.05), diabetes mellitus (OR, 2.4; 95% CI, 1.6 to 3.4; P < 0.001),
      urgent operation (OR, 1.7; 95% CI, 1.2 to 2.6; P < 0.05), smoking history within
      past year (OR, 2.7; 95% CI, 1.5 to 4.9; P < 0.001), smoking history within past 2
      weeks (OR, 2.6; 95% CI, 1.5 to 4.5; P < 0.001), and a history of stroke (OR, 1.9;
      95% CI, 1.1 to 3.1; P < 0.005). In addition, total length of hospital stay (OR,
      1.01; 95% CI, 1.01 to 1.02; P < 0.05) and sepsis and/or endocarditis following
      surgery (OR, 5.1; 95% CI, 2.9 to 9.0; P < 0.001) were also predictive of DSWI.
      Patients with DSWI had a prolonged total length of hospital stay (40.3 days
      versus 16.1 days; P < 0.001), and higher 30-day mortality (1.6% versus 7.3% in
      DSWI group, P < 0.05). There were no differences between groups in 4-year and 8
      year survival rates, with 77.2% and 61.8%, respectively, in patients with DSWI
      compared with 78.0% and 67.5% in patients without DSWI (P = 0.16). After
      adjustments for preoperative, intraoperative, and postoperative factors, the
      adjusted hazard ratio of long-term mortality for patients with DSWI was 0.9 (95%
      CI, 0.6 to 1.2, P = 0.39). Though DSWIs are associated with increased early
      mortality, patients undergoing cardiac surgery complicated by DSWI do not
      experience worse long-term survival.

PMID- 18724132
TI  - The design of the lateral thoracodorsal flap.
AB  - Although some of the aspects of the preoperative markings of the lateral
      thoracodorsal flap have been mentioned by its originators and subsequent authors,
      we get ongoing inquiries regarding the details of the design of the flap. These
      markings are made respecting the level of the contralateral nipple, with the
      convex inferior border of the flap extending up to the anterior axillary line,
      and with the straight superior border extending more medially over this line. We
      have used 200 lateral thoracodorsal flaps in 180 patients with no cases of more
      than marginal flap loss provided that the length of the flap was limited to a
      maximum of 17 cm. We found that this flap fills a therapeutic gap and provides a
      sound alternative to more extensive surgery.

PMID- 18724133
TI  - Chimeric gastrocnemius muscle and sural artery perforator local flap.
AB  - Under special circumstances, a chimeric form of combined flap can be
      advantageous. The formation of such a combination should be possible with any
      muscle perforator flap and its underlying muscle as a branch-based form of
      chimeric flap. In 2 patients with knee infections, this concept facilitated the
      use of local flaps only to simultaneously allow deep obliteration within the knee
      joint with the muscle portion while providing tension-free skin closure.
      Specifically, a chimeric gastrocnemius muscle and sural artery perforator flap,
      the latter based on either the medial or lateral sural source vessels, provided
      this reasonable solution. This is yet another new example of branch-based
      chimeric flaps, where the cutaneous component is a muscle perforator flap.

PMID- 18724134
TI  - A study of the effect of sartorius transposition on lymph flow after ilioinguinal
      node dissection.
AB  - Ilioinguinal dissection is associated with a high rate of lymphatic
      complications. Prolonged lymph flow causes greatest concern and preventive
      strategies are needed. A retrospective study of 28 consecutive patients
      undergoing groin dissection for melanoma metastases was performed to evaluate the
      influence of sartorius muscle transposition on lymph flow. Modification of the
      surgical technique with transposition of the sartorius muscle was not associated
      with reduced drainage time (P = 0.66). A 2-staged approach, with initial sentinel
      lymph node resection and lymph node dissection in a second operation, however,
      lead to shortened duration of the lymph flow (P = 0.01). Prolonged lymphorrhea
      was more frequent in older (P = 0.03), obese (P = 0.02) patients affected by
      diabetes mellitus (P = 0.03) and hypertension (P = 0.04).

PMID- 18724135
TI  - Influencing factors of outcome after lower-limb amputation: a five-year review in
      a plastic surgical department.
AB  - The crude major lower limb amputation procedure rate is 8.8 per 100,000 of the
      population per year in Taiwan. From January 2002 to October 2006, patients that
      received major lower limb amputation in our department were enrolled in this
      study. Retrospective chart reviews concerning different factors that can affect
      the eventual postoperative functional status were investigated. Factors that
      affected the length of hospital stay included duration before amputation (P <
      0.001) and renal function (P = 0.045). Phantom limb pain was affected by wound
      healing time (P = 0.006). Factors that affected the daily prosthesis usage time
      were initial infection status (P = 0.021), renal function (P = 0.01), patient
      educational level (P = 0.016), and pretraining waiting time (P = 0.003). The
      duration of prosthetic training was affected by patient educational level (P =
      0.004) and marital status (P = 0.024). In addition, subjective satisfaction about
      the usage of prosthesis was affected by pretraining waiting time (P = 0.001) and
      daily prosthesis usage time (P < 0.001). The daily prosthesis usage time was
      closely related to life quality improvement (P < 0.001) and subjective
      satisfaction of prosthesis usage (P < 0.001). Despite reported unchangeable
      factors like age, end-stage renal disease, dementia, coronary artery disease, and
      level of amputation, preprosthesis training waiting time significantly affected
      the satisfaction and daily usage time of the prosthesis. Surgeons can make some
      contribution to accelerate amputation wound healing and stump maturation by
      choosing the correct operating procedure, delicately managing the soft tissue,
      and ascertaining proper wound care to improve the outcome.

PMID- 18724136
TI  - Are reverse flow fasciocutaneous flaps an appropriate option for the
      reconstruction of severe postburn lower extremity contractures?
AB  - Full thickness burns involving the lower extremity can result in severe
      contractures, which impair extremity functions if they are not managed with
      proper treatment and rehabilitation. After release of postburn contracture of the
      knee, ankle, and metatarsophalangeal joints, defects often require coverage by
      flaps. Twelve distally based reverse flow flaps were performed for lower
      extremity reconstruction after release of postburn flexion contractures. All of
      the patients were male and their age ranged from 20 to 23 years, with a mean age
      of 21. After the release of the contractures, 3 flaps were used based on the
      location of the contractures. The reverse flow anterolateral thigh flap was used
      for knee reconstruction (n = 4, 33%). The reverse flow sural flap was used for
      ankle reconstruction (n = 4, 33%), and the reverse flow medial plantar flap was
      used for metatarsophalangeal reconstruction (n = 4, 33%). The sizes of the flap
      varied from 2 to 17 cm wide and 3 to 18 cm in length. All defects were covered
      successfully. Reverse fasciocutaneous tissue transfer to reconstruct the soft
      tissue defects provide early motion. Sufficient contracture release is achieved
      without displacement of anatomic landmarks. The reverse-flow flap is a reasonable
      and reliable choice for each joint level in the lower extremity.

PMID- 18724137
TI  - Gluteus maximus neural-island flap model in the rat.
AB  - Flaps that are supplied solely by intrinsic vasculatures of the nerves have been
      introduced; however, clinical applications of the muscle flaps have not been
      performed. Our aim in this study was to develop a neural-island muscle flap
      model. The study was composed of anatomic investigations (part I, n = 8),
      creation of the neural-island muscle flap model (part II, n = 40), and
      augmentation of the flap (part III, n = 20). After part I, we concluded that the
      gluteus maximus would be the most effective muscle for our model. In part II,
      gluteus maximus muscles were isolated on their motor nerves in 20 rats and, in
      the remaining 20, were harvested as grafts. A delay procedure was applied in part
      III.Average viability percentages of the graft group, acutely elevated group, and
      delayed group were 0.0% +/- 0.0%, 25.1% +/- 6.4% and 96.1% +/- 7.8%,
      respectively. This study provides a reliable muscle flap model that can be
      created as pedicled by the intrinsic vasculature of its motor nerve.

PMID- 18724138
TI  - Kappa-opioid receptor agonist protects the microcirculation of skeletal muscle
      from ischemia reperfusion injury.
AB  - BACKGROUND: Previous research has demonstrated that pretreatment with kappa
      opioid receptor (KOR) agonist protects against ischemia reperfusion (I/R) injury
      in cardiomyocytes and neuron cells through activation of protein kinase C. The
      purpose of this study is to investigate the KOR agonist's effect on I/R-injured
      cremaster muscle and its underlying mechanism. METHOD AND MATERIAL: Male Sprague
      Dawley rats were randomized into 3 groups (n = 6 each group). Group I was the
      ischemia reperfusion (I/R) injury group (4 hours of ischemia followed by 90
      minutes of reperfusion). Group II was the U-50488H (selective KOR agonist)
      pretreated group (KOR agonist + I/R injury). Group III was pretreated with U
      50488H + nor-binaltorphimine (NBI, a selective KOR antagonist) (KOR agonist +
      antagonist + I/R injury). The numbers of leukocyte rolling, adhering, and
      transmigrating, functional capillary, and swelling index of the vessel wall of
      the postcapillary venule were observed under intravital videomicroscopy.
      Biochemically, the lactate dehydrogenase, creatine phosphokinase isoenzyme,
      expression of E-selectin, and intercellular adhesion molecule-1 (ICAM-1) were
      analyzed. RESULTS: The U-50488H-pretreated group had significantly decreased the
      number of leukocyte sticking (P < 0.001) and transmigrating (P < 0.001) as
      compared with the I/R-injury group and the U-50488H + NBI-pretreated group. The
      numbers of functional capillary in the U-50488H-pretreated group were
      significantly less attenuated compared with the I/R-injury group and U-50488H +
      NBI-pretreated group (P < 0.001). The expression of the ICAM-1 in the cremaster
      muscle was evidently reduced in the U-50488H-pretreated group than in the I/R
      injury group or the U-50488H + NBI-pretreated group. CONCLUSION: Administration
      of KOR agonist protects the muscle flap microcirculation from I/R injury, which
      can be abolished by concomitant KOR antagonist administration. The KOR agonist
      induced protection from ischemia reperfusion injury may be related to decreased
      expression of adhesion molecule ICAM-1.

PMID- 18724139
TI  - Role of platelet-rich plasma in acceleration of bone fracture healing.
AB  - Platelet-rich plasma (PRP) is a common therapy for acceleration of maxillofacial
      and spinal fusion bone-graft healing. This study analyzes the therapeutic role of
      PRP during long-bone fracture healing evaluated Lewis rats. Following creation of
      unilateral open femur fractures, either 500 microL thrombin-activated PRP (PRP
      treated group) or 500 microL saline (control group) were applied once to the
      fracture site. Fracture healing was analyzed after 1 and 4 weeks. Following 4
      weeks of fracture healing, radiographic analysis demonstrated higher callus to
      cortex width ratio (P < 0.05) in the PRP group (PRP: 1.65 +/- 0.06; control: 1.48
      +/- 0.05). Three-point load bearing showed increased bone strength following PRP
      treatment (PRP: 60.85 +/- 6.06 Newton, control: 47.66 +/- 5.49 Newton). Fracture
      histology showed enhanced bone formation in the PRP group. Immunohistochemistry
      and Western-blotting demonstrated healing-associated changes in transforming
      growth factor (TGF)-beta1 and bone morphogenetic protein (BMP)-2. Our results
      suggest that PRP accelerates bone fracture healing of rat femurs via modulation
      of TGF-beta1 and BMP-2 growth factor expression.

PMID- 18724140
TI  - Face as an organ.
AB  - We propose that, the face should be regarded as an organ. We compare the anatomic
      structure and functions of the face with those of the kidney, one of the most
      commonly transplanted solid organs. Composite tissue allografts demonstrated to
      improve the quality of life. Although not classified as a life-essential
      transplant, face allotransplantation nevertheless constitutes a major
      reconstructive procedure. We emphasize the vital functions of the human face,
      underscoring that when these functions are jeopardized a patient's quality of
      life is compromised. In sum, although transplantation of solid organs is
      essential for a patient's physical survival, face allotransplantation is
      essential both for physical and social survival. Optimal social survival is what
      makes physical life worth living. Finally, when it comes to the gift of organ
      donation, it would be degrading to those signing the consent form to have the
      faces of their loved ones considered as merely skin.

PMID- 18724141
TI  - An easy way of obtaining symmetry in auricular surgery using rotated photographs.

PMID- 18724142
TI  - Outcome of treatment of mooren ulcer with topical cyclosporine a 2%.
AB  - PURPOSE: To study the clinical outcome of treatment of Mooren ulcer with topical
      cyclosporine A (CsA) 2% as an adjunct to standard therapy. METHODS: Seventeen
      eyes of 15 patients with Mooren ulcer treated with CsA 2% eyedrops were included.
      Five eyes had undergone a full-thickness patch graft for perforation and were
      started on topical CsA therapy after surgery. Topical CsA had been started in the
      other 12 eyes as an adjunct to standard medical therapy after treatment failure.
      Clinical efficacy was evaluated on the basis of reduction in lesion size, healing
      of the epithelial defect, visual recovery, and recurrence rate. RESULTS: In 12
      eyes to which topical CsA had been given as an adjunct therapy, the ulcers had
      resolved completely with various degrees of vascularization. The mean healing
      time including complete epithelization was 34.4 +/- 13.1 days (range, 14-56
      days). During the follow-up period of 12 months, recurrence had been observed in
      1 patient. No recurrence of the ulcer was seen in the 5 eyes that were started on
      topical CsA therapy after tectonic keratoplasty. A significant (P = 0.004)
      improvement was seen in the mean best-corrected visual acuity from the
      pretreatment values at 12 months. No adverse effects attributable to CsA were
      observed. CONCLUSIONS: Topical 2% CsA therapy can be a safe and useful adjunct to
      standard medical therapy in recalcitrant cases of Mooren ulcer.

PMID- 18724143
TI  - Comparison of central corneal thickness measurements by ultrasound pachymetry,
      konan noncontact optical pachymetry, and orbscan pachymetry.
AB  - PURPOSE: To assess the repeatability of two optical techniques for measurement of
      central corneal thickness and to compare the validity of these techniques with
      standard ultrasound pachymetry. METHODS: Corneal thickness was measured twice
      with Konan optical pachymetry, Orbscan optical pachymetry, and 3 times by
      conventional ultrasound pachymetry in 100 eyes of 50 healthy volunteers between
      the ages of 22 and 74 years. The repeatability of measurements of each instrument
      was determined and compared. Validity was determined by comparing the means of
      the first Konan and Orbscan measurements to the mean of standard ultrasound
      pachymetry. Intraclass correlation coefficients (ICCs) were calculated, and their
      confidence intervals (CIs) were determined. RESULTS: Repeatability of ultrasound
      pachymetry had an ICC of 0.905 (95% CI: 0.870-0.932). The Konan pachymeter had an
      ICC of 0.947 (95% CI: 0.922-0.964), and the Orbscan pachymetry yielded an ICC of
      0.972 (95% CI: 0.959-0.981). Validity of Konan pachymetry had an ICC of 0.730
      (95% CI: 0.623-0.810). Orbscan pachymetry had an ICC of 0.865 (95% CI: 0.805
      0.907). CONCLUSIONS: Both of the newer optical methods for determining corneal
      thickness produced measurements of greater repeatability than the standard
      ultrasound technique. Orbscan pachymetry provides greater repeatability (P =
      0.02) and validity (P = 0.007) than the Konan optical pachymeter.

PMID- 18724144
TI  - New test to quantify lipid layer behavior in healthy subjects and patients with
      keratoconjunctivitis sicca.
AB  - PURPOSE: Diagnostic procedures currently available to evaluate tear film lipid
      layer alterations are of limited application and do not provide quantitative
      results. The purpose of this prospective, case-control study was to develop a
      noninvasive test to measure tear lipid behavior in healthy subjects and patients
      with dry eye. METHODS: The dynamic lipid layer interference patterns (DLIP) test
      was performed on 21 patients with dry eye and 21 age-matched controls. Subjects
      in the study and control groups were asked to perform 5 forced blinks and 10
      consecutive nonforced blinks every 2 seconds to load lipids from the palpebral
      reservoir into the tear film. After recording the lipid layer interference
      patterns obtained with the Tearscope, a masked investigator counted the number of
      blinks to observe significant changes of shape, position, and number of waves of
      the interference patterns. Patients with dry eye were identified on the basis of
      the typical symptoms measured by a validated questionnaire (Ocular Surface
      Disease Index questionnaire score >10), Schirmer I test scores <10 mm/5 min, tear
      breakup time (TBUT) <7 seconds, and lissamine green conjunctival staining >4.
      RESULTS: Significant differences in Schirmer test, TBUT, and lissamine green were
      recorded between groups. The DLIP test in the dry eye group (2.4 +/- 3.1 blinks)
      was statistically decreased compared with the control group (18.1 +/- 5.9 blinks;
      P < 0.0001, t test). A significant Pearson correlation (r = 0.788) was found
      between the DLIP test and TBUT. The receiver operating characteristic curve
      defined a cutoff value of 6.5 blinks to separate healthy from dry eyes
      (sensitivity of 100%, specificity of 95%). CONCLUSIONS: The DLIP is a new test
      that can be used in clinical practice to quantify tear film lipid layer behavior
      and to diagnose dry eye.

PMID- 18724145
TI  - Visual improvement after late debridement of residual stroma after anterior
      lamellar keratoplasty.
AB  - PURPOSE: This was an observational consecutive noncomparative series of cases.
      The main outcome measure was recovery of best-corrected vision. The purpose of
      this study was to show the feasibility of enhancing visual outcome in patients
      operated with anterior lamellar keratoplasty (ALK) who have not achieved an
      adequate visual outcome. METHODS: Four eyes of 4 patients with poor visual
      recovery after ALK, with no obvious reasons to justify the outcome. RESULTS: All
      patients improved at least 4 lines of best-corrected vision (from preoperative
      mean of 20/80 to postoperative mean of 20/25) after removal of the posterior
      residual stromal bed. No complications occurred. CONCLUSIONS: Removal of the
      posterior lamellar layers is feasible even 2 years after ALK and recovers best
      corrected visual acuity in cases with no other cause of poor visual outcome after
      ALK.

PMID- 18724146
TI  - Topographic evaluation of relatives of patients with keratoconus.
AB  - PURPOSE: To evaluate topographic corneal changes in relatives of patients with
      keratoconus (KCN). METHODS: In a prospective study, 300 eyes of 150 relatives of
      45 patients with KCN were evaluated. Complete slit-lamp examination, refraction,
      and corneal topography were performed for all eyes. The topographic indices for
      diagnosis of KCN were from Rabinowitz criteria. RESULTS: The study included 84
      (56%) female and 66 (44%) male subjects. Mean age was 32.4 +/- 15 years (range,
      16-83 years). KCN was diagnosed in 14% of the subjects and another 7.3% were
      suspicious for KCN. The overall prevalence of astigmatism was 58%, including
      42.1% in the KCN group, 66.7% in the KCN suspect group, and 49.6% in the healthy
      group. Thirty-one eyes had high regular astigmatism (>1.5 D) including 17 (54.8%)
      in the KCN group and 14 (45.2%) in the healthy group. Oblique astigmatism was
      seen in 33 (11%) eyes, including 34.2% in the KCN group, 47.6% in the suspicious
      KCN group, and 4.6% in the healthy group. CONCLUSIONS: Relatives of patients with
      KCN have a high prevalence of undiagnosed KCN. Corneal topography is important
      for the diagnosis of KCN and KCN suspects in family members of patients with KCN.
      Therefore, keratorefractive surgery should be considered cautiously in these
      individuals.

PMID- 18724147
TI  - Mapping of normal corneal K-structures by in vivo laser confocal microscopy.
AB  - PURPOSE: To produce 2-dimensional reconstruction maps of normal human corneal
      fibrous structures beneath the Bowman layer (K-structures) by in vivo laser
      confocal microscopy and to show association of structures with the anterior
      corneal mosaic (ACM). METHODS: Central corneal regions of 3 healthy volunteers
      were scanned. Acquired images of K-structures for each eye were arranged and
      mapped into a subconfluent montage. For each subject, electrical tracings of K
      structures were superimposed on a slit-lamp photograph of the ACM produced by
      rubbing the eyelid. RESULTS: A mean of 677 +/- 211 images of K-structures were
      obtained for each eye. Mean dimensions of the mapped areas were 5.88 +/- 0.50
      (horizontal) and 3.51 +/- 1.37 mm (vertical). In all subjects, K-structures
      formed a netlike pattern (mean area, 0.082 +/- 0.051 mm), and electrical tracings
      had good concordance with the ACM. CONCLUSIONS: This is the first study, to our
      knowledge, to elucidate the overall distribution of K-structures in normal human
      corneas. The netlike pattern of K-structures corresponded well with ACM pattern.
      These results support the hypothesis that the K-structures are the anterior
      collagen fiber bundles running at the posterior surface of the Bowman layer and
      thus are the structural basis for ACM formation.

PMID- 18724148
TI  - Use of systemic T-lymphocyte signal transduction inhibitors in the treatment of
      atopic keratoconjunctivitis.
AB  - PURPOSE: Topical immunomodulators such as tacrolimus have revolutionized the
      treatment of atopic dermatitis. Because T lymphocytes are integral to the
      pathogenesis of atopic dermatitis, systemic treatment with T-lymphocyte signal
      transduction inhibitors should ameliorate both the dermatologic and ocular
      manifestations. We describe the successful treatment of 6 patients with severe
      atopic keratoconjunctivitis (AKC) resistant to conventional therapies. METHODS:
      Retrospective observational case series. The charts of patients with AKC assessed
      by 1 of the authors were reviewed to identify those treated with systemic T-cell
      signal transduction inhibitors. Visual acuities, previous treatments, and the
      response to systemic signal transduction inhibitors were observed and reported in
      6 patients. RESULTS: The patients had a mean duration of AKC of 21 years. Topical
      corticosteroids and antihistamines had failed to control signs and symptoms of
      the disease in all patients, and in some patients, systemic corticosteroids and
      topical cyclosporine were ineffective. Three patients were treated with systemic
      cyclosporine, and 3 were treated with systemic tacrolimus. One patient was
      subsequently treated with daclizumab in addition to tacrolimus. All 6 patients
      experienced complete remission of their AKC and an increase in visual acuity.
      CONCLUSIONS: Selective systemic immunosuppression of T lymphocytes with
      cyclosporine or tacrolimus has proved effective in the treatment of both atopic
      dermatitis and atopic keratoconjunctivitis. We advocate the consideration of
      systemic therapy in cases that are resistant to conventional treatment to resolve
      inflammation and preserve vision. Further studies in this area are advocated.

PMID- 18724149
TI  - A comparison of corneal endothelial cell changes after 1-site and 2-site
      phacotrabeculectomy.
AB  - PURPOSE: To compare the corneal endothelial cell (CEC) changes that occurred
      after phacotrabeculectomy performed at 1 or 2 sites. DESIGN: A historical cohort
      study. METHODS: The records of patients who had 1-site (n = 61) or 2-site (n =
      52) limbus-based phacotrabeculectomy over a 4-year period (2002-2005) at 1 eye
      surgery center (Vanak Eye Surgery Center, Tehran, Iran) by a single surgeon were
      reviewed, and postoperative CEC indices were measured. Preoperative CEC indices,
      performed for a then-ongoing trial, were compared with postoperative measurements
      of the last follow-ups. The main outcome measure was endothelial cell count.
      RESULTS: The median follow-up time was 12 months (range 9-24 months). There was
      no difference between the operations in improving visual acuity, lowering
      intraocular pressure, and decreasing the number of antiglaucoma medications
      required. However, 2-site surgery was associated with significantly more
      expansion in the CEC area (P < 0.001). On multivariate analysis, longer follow
      up, 2-site surgery, and grade 4 cataract density were independently associated
      with more CEC loss, and longer follow-up, 2-site surgery, and steroid-induced
      glaucoma were associated with CEC area expansion. Postoperative complications
      were not markedly different between the 2 groups. CONCLUSIONS: In both groups,
      the longer the follow-up time was, the higher the CEC loss and the CEC area
      expansion were. One-site surgery seems to cause less CEC damage than the 2-site
      operation during the median follow-up time of 1 year.

PMID- 18724150
TI  - Incidence and clinical characteristics of enterococcus keratitis.
AB  - PURPOSE: To study the incidence, clinically relevant factors, and antibiotic
      sensitivity profile of cases of enterococcal keratitis presenting at the New York
      Eye and Ear Infirmary between January 1, 1996, and December 31, 2005. METHODS:
      The records of all corneal cultures submitted to the Microbiology Laboratory of
      the New York Eye and Ear Infirmary between January 1, 1996, and December 31,
      2005, were reviewed. All cases that were positive for Enterococcus species were
      identified, and the corresponding patients' medical records were obtained and
      studied. RESULTS: There were 15 cases of enterococcal keratitis identified during
      the study period, and all were E. faecalis species. The age of the patients
      ranged from 17 to 98 years (mean age, 57.5 years). Twelve of the patients were
      women. Two patients developed keratitis in existing corneal grafts. Two patients
      were on topical steroid medications, with 1 having an existing corneal graft.
      Fourteen of the 15 had abnormalities of the ocular surface or wore contact
      lenses. Eight (53%) of the patients were soft contact lens wearers. Only 1 case
      was directly attributable to trauma. Fourteen (93%) of the bacterial isolates
      were sensitive to vancomycin. One case had intermediate sensitivity. Eleven cases
      resolved with topical antibiotics, 3 cases required penetrating keratoplasty, and
      in 1 case, the outcome is unknown. CONCLUSIONS: Enterococcus faecalis keratitis
      is associated with abnormalities of the corneal surface and contact lens wear.
      Most of the isolates were sensitive to vancomycin, although 1 was of intermediate
      sensitivity, the importance of which is not known.

PMID- 18724151
TI  - Histopathology of posterior lamellar endothelial keratoplasty graft failure.
AB  - PURPOSE: To describe the histopathologic findings and relevant clinical details
      of 3 patients undergoing penetrating keratoplasty (PK) after failure of posterior
      lamellar endothelial keratoplasty (EK). METHODS: Retrospective clinicopathologic
      case series. Patients 1 and 2 underwent EK for pseudophakic bullous keratopathy.
      Patient 3 underwent EK for persistent corneal edema secondary to a Descemet
      membrane (DM) detachment after cataract extraction. Patient 1 had persistent
      diffuse corneal edema and broad, long-standing iridocorneal adhesions that
      precluded repeat EK. Patient 2 had high intraocular pressure and severe anterior
      chamber inflammation 1 day postoperatively with subsequent noncorneal clearing
      and elected PK over repeat EK. Progressive corneal edema with resultant poor
      visual acuity after EK was the reason for PK in patient 3. RESULTS:
      Histopathologic examination disclosed thickened, edematous corneas with
      attenuated endothelium consistent with graft failure caused by endothelial
      decompensation in all 3 cases. Although various degrees of posterior lamellar
      graft detachment were observed in each instance, significant parts of each graft
      remained adherent to the host stroma or to segments of residual host DM. The
      wounds in the adherent areas, although discernible, were relatively
      inconspicuous, resembling those seen at the flap-stromal interface after laser in
      situ keratomileusis. The donor graft endothelium was atrophic in all cases, and a
      delicate retrocorneal fibrous membrane was present in 2 cases. Most of the graft
      in cases 1 and 2 remained adherent, with small areas of peripheral detachment. In
      contrast, the graft in case 3 adhered peripherally but had separated from the
      stroma centrally, forming a thin cleft. CONCLUSIONS: Histopathology suggests
      endothelial decompensation, incomplete graft adherence, and the formation of
      retrocorneal fibrous membranes as possible etiologies for EK failure. The
      adherence of endothelial grafts to residual host DM suggests that it may not be
      necessary to remove optically clear DM before endothelial graft placement. The
      inconspicuous nature of the EK interface suggests that it may not play a large
      role in image degradation, although more study is needed.

PMID- 18724152
TI  - AlphaCor keratoprosthesis: a novel approach to minimize the risks of long-term
      postoperative complications.
AB  - PURPOSE: To describe clinical outcomes of patients who underwent implantation of
      the AlphaCor keratoprosthesis, without the second stage of the procedure, in
      which the central anterior layer of the corneal stromal pocket is excised to
      expose the keratoprosthesis optic to the exterior of the eye. METHODS: Outcomes
      of 6 consecutive cases of AlphaCor implantation without the second stage of the
      procedure were retrospectively reviewed. The cases were performed at 1 tertiary
      referral center between February 2005 and December 2006. RESULTS: Each of the 6
      treated eyes had experienced failure of 2-5 human donor grafts before AlphaCor
      implantation. With a mean follow-up of 22 months (range, 14-38 months), all
      devices remained in situ at time of review. All patients had decreased pain
      compared with what they experienced preoperatively, and preoperative bullous
      keratopathy resolved after AlphaCor implantation. Two patients developed
      retroprosthetic membranes. Five patients developed elevated intraocular pressure
      requiring additional medication or surgery in the postoperative course, but 4 of
      them had preexisting glaucoma. No patients developed breakdown of the ocular
      surface, increased ocular surface disease, stromal melting, aqueous leakage,
      infection, or extrusion. CONCLUSIONS: Omitting stage 2 surgery of the AlphaCor
      implantation may decrease the incidence of complications and provide patients
      with a comfortable eye and improved cosmetic appearance in cases of bullous
      keratopathy from corneal graft failure and can be useful when there is little
      chance of a successful repeat graft and no urgency or possibility of restoring
      visual acuity better than approximately 20/200. Resolution of bullous keratopathy
      and reduction of pain was achieved despite the lack of functional endothelium.

PMID- 18724153
TI  - Biological glue in pterygium surgery with a rotational flap or sliding flaps.
AB  - PURPOSE: To compare 2 surgical approaches to conjunctival flap placement during
      pterygium surgery using a biologic adhesive: single rotational flap and double
      sliding flaps. METHODS: Thirty-three consecutive patients (34 eyes) with primary
      pterygium were assigned prospectively and randomly to receive pterygium surgery
      with either 1 rotational flap (group A, 19 eyes) or double sliding flaps (group
      B, 15 eyes) by using a biologic adhesive to secure the flaps. The patients were
      followed for 24 weeks. RESULTS: In group A, 1 (5.3%) flap was lost because of
      ischemia, whereas all the others remained in position and became fully
      integrated. In group B, 4 (26%) flaps did not retain their primary position. In 2
      (13%) eyes, the superior and inferior flaps partially dehisced, resulting in a 2-
      to 3-mm gap; in 1 (6.5%) eye, the inferior flap dehisced completely and retracted
      to the lower fornix; and in 1 (6.5%) eye, both flaps completely dehisced and
      retracted, leaving an area of bare sclera. CONCLUSIONS: The use of tissue
      adhesive is a promising technique in pterygium surgery. In this study, gluing 1
      rotational flap resulted in excellent postoperative results, but it seemed less
      suitable for use with double sliding flaps.

PMID- 18724154
TI  - Protective effect of ascorbic Acid against corneal damage by ultraviolet B
      irradiation: a pilot study.
AB  - PURPOSE: To determine the protective effect of ascorbic acid (ASA) against
      corneal damage by ultraviolet B (UVB) irradiation. METHODS: Eight rabbits
      weighing 2.1-2.5 kg were randomly divided into 3 groups: a UVB group, an ASA
      group, and a control group. The UVB group was made up of 2 rabbits that were
      exposed to 6.84 J/cm of UVB irradiation at a peak wavelength of 306 nm for 17
      min/d for 7 days. The ASA group was made up of 4 rabbits that were pretreated
      intravenously with ASA before being subjected to UVB irradiation. The control
      group was made up of 2 rabbits that were not subjected to ASA treatment or UVB
      exposure. After 7 days, the corneas were clinically evaluated for signs of
      epithelial damage, corneal haze, and neovascularization. After evaluation, the
      enucleated eyes were analyzed pathologically for signs of proliferation, nuclear
      change, inflammation, edema, and neovascularization. RESULTS: More damage was
      observed in the irradiation groups (UVB and ASA groups) than in the control group
      for all clinical and pathologic parameters (P < 0.0001). Also, when each of the
      parameters was considered, more severe changes were observed in the UVB group
      than the ASA group (P < 0.0001), with the exception of nuclear changes, for which
      the comparison was not applicable. CONCLUSIONS: ASA protected the cornea against
      UVB irradiation in this pilot study; however, further evaluation using many
      animals is needed to establish its efficacy.

PMID- 18724155
TI  - Corneal abnormalities in the NC/Nga mouse: an atopic dermatitis model.
AB  - PURPOSE: To study corneal abnormalities in the NC/Nga mouse, which is an animal
      model of atopic dermatitis. METHODS: To study histopathologic changes of the
      eyelid, conjunctiva, and cornea, we extracted the eyeballs together with upper
      and lower eyelids and fixed them for examination by light and electron microscopy
      or snap-froze them for immunohistochemistry. Transferase mediated-dUTP
      digoxigenin nick-end labeling staining was performed to detect apoptotic cells.
      In order to assess eye scratching behavior and the effect of tacroliums hydrate
      ointment, we made video recordings. RESULTS: Mice kept in a conventional room
      suffered from various grades of blepharoconjunctivitis and scratched their eyes
      furiously. Tacrolimus hydrate ointment reduced their eye-scratching behavior.
      Histopathologic study of the eyelid and conjunctiva showed that this
      blepharoconjunctivitis was caused by allergic inflammation. Mice with severe
      blepharoconjunctivitis showed thinning of the corneal epithelium, an irregular
      interface between the epithelium and stroma, subepithelial deposition of
      materials, and neovascularization of the stroma. Their corneas were cone shaped.
      Many transferase mediated-dUTP digoxigenin nick-end labeling-positive cells were
      recognized among superficial epithelial cells and keratocytes. CONCLUSIONS:
      NC/Nga mice are a useful animal model of atopic blepharoconjunctivitis. Various
      corneal disorders in these mice may depend on their eye-scratching behavior.

PMID- 18724156
TI  - Evaluation of toxicity of commercial ophthalmic fluoroquinolone antibiotics as
      assessed on immortalized corneal and conjunctival epithelial cells.
AB  - PURPOSE: To evaluate the toxicity of a variety of the fluoroquinolone antibiotics
      on the ocular surface by using tissue culture models of corneal epithelial cells
      and conjunctival epithelial cells. METHODS: Immortalized conjunctival (CCC) and
      human corneal (HCE) epithelial cells were grown and when confluent the cells
      allowed to air dry for 1 hour. Medium was then replaced with 100 microL of one of
      the following: 1) Vigamox [moxifloxacin (0.5%: MX)]; (2) Zymar [gatifloxacin
      (0.3%: GA)]; 3) Quixin [levofloxacin (0.5%: LE)]; 4) Ocuflox [ofloxacin (0.3%:
      OF)]; 5) Ciloxan [ciprofloxacin (0.3%: CP)]; 6) medium (viable control); 7)
      "normal"/physiologic saline; 8) formalin (dead control). After one hour, 150
      microL of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazonium bromide was
      added and incubated for 4 hours. After decanting, precipitate was dissolved in
      150 microL of isopropanol. Absorbance was determined at 572 nm. RESULTS: The
      lowest amount of cell death was associated with the viable control. All
      ophthalmic preparations showed both corneal and conjunctival cell toxicity. Aside
      from the viable control, normal saline showed the next lowest amount of toxicity.
      Of the topical ocular antibiotics tested, MX showed the least amount of toxicity.
      All of the other antibiotics tested were statistically indistinguishable from
      each other. CONCLUSIONS: All of the topical ocular antibiotics tested showed
      evidence of both corneal and conjunctival toxicity (MX < OF < or = LE < or = CP <
      or = GA), although only MX was statistically significant. Whether this finding
      reflects on in vivo wound healing remains to be determined. This model provides a
      rapid and cost-effective method to screen for surface toxicity of topical agents.

PMID- 18724158
TI  - Descemet-stripping automated endothelial keratoplasty: insertion using a novel
      40/60 underfold technique for preservation of donor endothelium.
AB  - PURPOSE: To describe a technique for insertion of an asymmetrically folded donor
      graft to minimize endothelial damage during Descemet-stripping automated
      endothelial keratoplasty. METHODS: The tissue is folded in a 40/60 underfold
      rather than the commonly used 60/40 overfold. It is then grasped with the
      insertion forceps by using a prone hand position. The hand is rotated clockwise
      until it is supine, bringing the 60% side of the fold anteriorly, and then the
      tissue is inserted into the anterior chamber. RESULTS: In 112 eyes, conventional
      60/40 overfold insertion technique resulted in a 36% loss in endothelial cell
      density at 6 months. In 36 eyes, the new 40/60 underfold technique results in a
      26% cell loss. This difference of 10% was statistically significant (P = 0.001).
      CONCLUSIONS: This simple modification to a commonly used folding technique
      reduces trauma to the exposed peripheral endothelium in a 60/40 overfolded
      "taco," which is due to contact with the donor trephine block or other surface.
      It is a slight modification to a commonly used technique for graft insertion and
      can be easily implemented to reduce postoperative endothelial cell loss.

PMID- 18724157
TI  - Desiccating stress decreases apical corneal epithelial cell size--modulation by
      the metalloproteinase inhibitor doxycycline.
AB  - PURPOSE: We investigated the effects of desiccating stress on murine corneal
      apical epithelial cell area and desquamation by using 4 defined parameters and
      evaluated the effects of the metalloproteinase inhibitor doxycycline on this
      process. METHODS: C57BL/6 mice were subjected to experimental dry eye (EDE) for 5
      days without or with topical therapy with doxycycline 0.025% or 0.0025% or
      vehicle 4 times a day. C57BL/6 mice that were not exposed to desiccating stress
      served as controls. Whole mount corneas from each group were immunostained for
      occludin and visualized by laser scanning confocal microscopy. The images were
      analyzed in a masked fashion, and mean individual cell area, apical cell density,
      average cell number loss, and average percent loss were recorded. RESULTS: EDE
      caused a significant decrease in apical corneal cell area (1073 +/- 135.9
      microm2), an increase in apical cell density (895.8 +/- 115.4 cells per mm2) and
      a greater percent of epithelial loss (21.29% +/- 13.40%) than controls (1341 +/-
      95.28 microm2, 714.4 +/- 55.60 cells per mm2, 2.897% +/- 3.452%, P < 0.001 for
      all, respectively). Treatment with 0.025% doxycycline preserved cell area (1337
      +/- 144.6 microm2) and the apical cell density (721.0 +/- 91.62 cells per mm2)
      and decreased percentage loss (5.117% +/- 6.757%) compared with the vehicle
      control group (1154 +/- 88.10 microm2, 830.2 +/- 49.76 cells per mm2, 22.14 +/-
      9.616%, P < 0.001 for all, respectively). CONCLUSIONS: Desiccating stress
      decreases apical corneal epithelial cell area, increases apical cell density, and
      promotes epithelial cell loss. Treatment with the metalloproteinase inhibitor
      doxycycline during desiccating stress preserves cell area and apical cell density
      and prevents EDE-induced corneal epithelial cell loss. These findings suggest
      that metalloproteinases mediate apical corneal epithelial loss during desiccating
      stress.

PMID- 18724159
TI  - Papillary conjunctivitis associated with Kikuchi disease.
AB  - PURPOSE: To describe a case of papillary conjunctivitis associated with Kikuchi
      Fujimoto disease (KFD). METHODS: Case report. RESULTS: A 35-year-old black man
      developed bilateral eye redness before developing high fevers and cervical
      lymphadenopathy. Mediastinoscopy confirmed the diagnosis of KFD. The eye redness
      resolved on a regimen of prednisone 60 mg daily and recurred after
      corticosteroids were discontinued. The patient was found to have bilateral
      papillary conjunctivitis that resolved with topical prednisolone acetate.
      CONCLUSIONS: Papillary conjunctivitis may be associated with KFD.

PMID- 18724160
TI  - Listeria monocytogenes sclerokeratitis: a case report and literature review.
AB  - PURPOSE: To report a case of Listeria monocytogenes sclerokeratitis and to review
      the literature. METHODS: Case report. RESULTS: A 25-year-old non-contact lens
      wearing male rugby player was referred with progressive infective sclerokeratitis
      unresponsive to topical antivirals and antibiotics. On examination, visual acuity
      was perception of light, and a large corneal abscess with overlying epithelial
      defect and hypopyon was present. The corneal lesion was cheesy white and raised
      with nasal scleritis. This raised the suspicion of a fungal keratitis. Empirical
      treatment with intensive topical antifungals was unsuccessful. A previous corneal
      scrape had been negative for bacteria and fungi. A corneal biopsy was performed,
      and Listeria monocytogenes was eventually isolated from enrichment culture.
      Antibiotic sensitivities showed it to be resistant to cefuroxime, methicillin,
      and ceftazidime but sensitive to all other antibiotics tested including
      ofloxacin. The treatment course was complicated by a corneal perforation that
      needed an emergency therapeutic penetrating keratoplasty. Five months later, best
      corrected visual acuity was 6/9 + 4, with a clear functioning graft. CONCLUSIONS:
      Listeria monocytogenes is a rare cause of corneal/scleral infection in humans. It
      often runs an aggressive course and responds poorly to initial intensive
      antibiotic treatment despite favorable in vitro sensitivities. It can be
      difficult to culture, and we suggest a corneal biopsy with extended incubation to
      improve diagnostic yield.

PMID- 18724161
TI  - Novel use of fibrin glue in the treatment of conjunctivochalasis.
AB  - PURPOSE: To report on the novel use of fibrin glue in the treatment of
      conjunctival resection for conjunctivochalasis. METHODS: A 78-year-old woman with
      bilateral, symptomatic conjunctivochalasis had a conjunctival resection by using
      fibrin glue, as a suture substitute, to attach the conjunctiva. RESULTS: The use
      of fibrin glue facilitated the surgical procedure, was well tolerated by the
      patient, and produced excellent results with relief of symptoms. CONCLUSIONS: The
      use of fibrin glue during the conjunctival resection was effective in simplifying
      the procedure and theoretically decreased the risk of suture-related
      complications and the postoperative irritation related to the presence of sutures
      in situ.

PMID- 18724162
TI  - Deep lamellar keratoplasty for pellucid marginal degeneration: review of
      management options for corneal perforation.
AB  - PURPOSE: To report a case of unilateral corneal perforation associated with
      pellucid marginal degeneration (PMD) and rapid onset and progression of PMD in
      the second eye. Both eyes underwent subsequent successful management with deep
      anterior lamellar keratoplasty (DALK). METHODS: Case presentation with corneal
      topographic correlation, along with the relevant literature pertaining to
      surgical techniques used in PMD. RESULTS: DALK was undertaken in both eyes with
      stable improvement in visual outcome and no rejection episode. CONCLUSIONS: DALK
      is a useful surgical alternative in the management of PMD. The technique provides
      useful visual rehabilitation in patients with PMD even in the presence of
      previous corneal perforation.

PMID- 18724163
TI  - Corneal-conjunctival squamous cell carcinoma.
AB  - PURPOSE: To report an extremely rare case of an extensive conjunctival-corneal
      invasive squamous cell carcinoma. METHODS: A healthy 68-year-old man referred to
      our department with a moderately elevated hyperemic nodular mass on his right
      ocular surface. The lesion was completely covering the corneal surface and
      involved the temporal limbus with bulbar conjunctiva. Surgical excision was
      performed with 2-mm tumor-free margins documented histologically and double
      freeze cryotherapy was applied 360 degrees for inhibition of tumor recurrence.
      RESULTS: Histopathologic examination showed a moderately differentiated squamous
      cell carcinoma. The patient achieved a complete excision with no evidence of
      recurrence during the follow-up period of 12 months. CONCLUSIONS: This case
      points out the potential for a total covering of the cornea by squamous cell
      carcinoma. Wide surgical excision and double freeze-thaw cryotherapy may decrease
      the recurrence.

PMID- 18724164
TI  - Topical fusidic acid for treatment of Clostridium perfringens Keratitis.
AB  - PURPOSE: To report the therapeutic outcome of primary corneal infection by
      Clostridium perfringens. METHODS: A 65-year-old cleaning lady had pain, decreased
      visual acuity, redness, and photophobia in her left eye for 4 days. A paracentral
      corneal ulcer with subepithelial bullae and several frothy bubbles in the ulcer
      bed was found. Two different cultures were positive for C. perfringens. RESULTS:
      Treatment with topical fusidic acid 1% was given, and the corneal infiltrate
      regressed within 6 weeks to a faint corneal opacity. CONCLUSIONS: Clostridium
      perfringens keratitis can be treated successfully with topical fusidic acid.

PMID- 18724166
TI  - Scheimpflug photographic diagnosis of pellucid marginal degeneration.
AB  - PURPOSE: We present a case of advanced bilateral pellucid marginal degeneration
      (PMD) with unilateral hydrops to show the unique properties of Scheimpflug
      imaging and its ability to display the clinical and topographic findings of PMD
      not seen on traditional placido-based topography. METHODS: Case report and
      literature review. RESULTS: A 51-year-old man was referred with a presumptive
      diagnosis of bilateral keratoconus with unilateral hydrops. Complete topographic
      evaluation showed a band of inferior thinning adjacent to the limbus and a
      Scheimpflug cross-sectional image consistent with PMD. CONCLUSIONS: We show the
      value of Scheimpflug-based topography and pachymetry maps to accurately depict
      the unique disease characteristics of PMD.

PMID- 18724165
TI  - Corneal perforation and delayed anterior chamber collapse from a devil's club
      thorn.
AB  - PURPOSE: To report the corneal perforation and delayed collapse of the anterior
      chamber caused by the thorn from a devil's club plant. METHODS: An 8-year-old
      Alaska Native girl was struck in the eye with the stalk and leaves of a devil's
      club plant. Although 3 thorns from the plant were found to be lodged
      superficially in the corneal stroma, 1 was deeply embedded to the level of
      Descemet's membrane. The thorn was surrounded by a stromal infiltrate. Four days
      after the injury, the patient suffered a sudden collapse of the anterior chamber
      after the deeply embedded thorn became dislodged. RESULTS: The corneal wound was
      sutured, and the patient had an uneventful postoperative course. CONCLUSIONS: Our
      experience suggests that devil's club corneal injuries should be examined daily
      after the initial injury. The anterior chamber may suddenly collapse after a
      deeply embedded thorn becomes dislodged.

PMID- 18724167
TI  - Intravenous immunoglobulin therapy for refractory ocular cicatricial pemphigoid:
      case report.
AB  - PURPOSE: To report the favorable outcome of a patient with severe ocular
      cicatricial pemphigoid, which was refractory to conventional treatment but
      recovered after intravenous immunoglobulin therapy. METHODS: A case report.
      RESULTS: Conventional therapy failed to control the ocular symptoms of this
      patient, which are typical of the disease. However, the patient improved
      remarkably in response to pulsed intravenous human immunoglobulin therapy.
      CONCLUSIONS: We achieved stabilization of the disease around the seventh
      intravenous immunoglobulin cycle, thus contributing to satisfactory postoperative
      evolution after limbal allograft transplantation and facilitating the performance
      of intraocular surgical procedures, such as phacoemulsification, with improvement
      in best-corrected visual acuity.

PMID- 18724168
TI  - Absence of cornea verticillata in hemizygotes of a novel mutation in fabry
      disease.
AB  - PURPOSE: To report a new pedigree of Fabry disease that does not display corneal
      involvement in hemizygotes. METHODS: A 44-year-old man presented with
      proteinuria, chronic obstructive airway disease, hypoacusia, teleangiectasis, and
      hypohidrosis. A kidney biopsy, genetic study, and ophthalmological examination
      were conducted. The patient's 66-year-old mother and 45-year-old sister were also
      investigated. RESULTS: Glomerular changes associated with Fabry disease were
      found. The diagnosis was confirmed by genetic study of the alpha-galactosidase A
      gene. In exon 2, an adenine was changed to a guanine at codon 92. This mutation
      is called D92G or Asp92Gly. This mutation has not been reported previously.
      Systemic examination showed cardiac involvement and chronic obstructive airway
      disease in the mother of the patient. The same mutation was present in the mother
      and in the sister of the patient. Cornea verticillata was not present in the
      hemizygous male. The mother and the sister of the patient showed the features of
      cornea verticillata. The patient and his mother were treated with enzyme
      replacement therapy using recombinant alpha-galactosidase A. CONCLUSIONS: We
      report here a new mutation in Fabry disease. The hemizygote did not show corneal
      manifestations as opposed to heterozygotes in the described family. The severity
      of systemic disease was not correlated with the presence of corneal deposits.

PMID- 18724169
TI  - An outbreak of fusarium keratitis associated with contact lens use in the
      northeastern United States.

PMID- 18724171
TI  - Vitamin a deficiency.

PMID- 18724173
TI  - An overview of sepsis.
AB  - The purpose of this paper was to briefly define sepsis, severe sepsis, and septic
      shock and discuss evidence-based guidelines for implementing a sepsis protocol in
      the critical care setting. In addition, this article will further educate
      critical care nurses about sepsis and strategies to improve outcomes in this
      group of patients.

PMID- 18724175
TI  - Ultrasound-assisted drug delivery for treatment of venous thrombosis: a case
      study.
AB  - Ultrasound-assisted drug delivery is a relatively new medical intervention that
      combines low-intensity ultrasound waves with infusion of a thrombolytic agent
      directly into a thrombosed vein. Studies have demonstrated that clots are
      eradicated faster, more completely, and with fewer bleeding events with the use
      of ultrasound-assisted drug delivery for treatment of deep vein thrombosis
      compared to that of traditional therapies. Critical care nurses are responsible
      for preprocedure assessment and teaching and continuous monitoring of the patient
      during therapy for effectiveness and potential complications. An advantage of
      this technology from a nursing perspective is the minimal amount of time required
      for monitoring the drug delivery system, allowing greater focus on patient
      assessment and care.

PMID- 18724176
TI  - Cardiac syndrome X: a brief overview for nurses.
AB  - Cardiac syndrome X is characterized by typical anginal symptoms and a positive
      exercise stress test in patients with normal coronary arteries confirmed by
      angiography. It is a relatively common condition seen by nurses working with
      patients undergoing cardiac catheterization. This article briefly describes the
      condition, pathophysiology, and treatment options. Nursing interventions in the
      care of these patients are also discussed.

PMID- 18724178
TI  - A personal reflection: critical care family communication.
AB  - Having a child hospitalized in a pediatric intensive care unit is very
      frightening and stressful for the parents. This second of a 2-part article
      discusses the development of "The Family Survival Guide to the Intensive Care
      Unit." This article is meant as a resource for critical care nurses.

PMID- 18724179
TI  - Innovative solutions: family presence at codes: a protocol for an oncology unit.
AB  - Family presence at codes is a concept that often elicits differing opinions from
      healthcare workers with regard to implementation, evaluation, and efficacy of the
      process. The oncology nursing service at Banner Good Samaritan Medical Center
      created a protocol to operationalize the guidelines of family presence at codes.
      The protocol was based on the Emergency Nurses Association guidelines from 2001
      and modified to complement the current practice environment and culture of the
      units. Evaluation surveys were created for both the family members present and
      staff involved in the process.

PMID- 18724183
TI  - National Heart, Lung, and Blood Institute issues first US von Willebrand disease
      clinical practice guidelines.

PMID- 18724181
TI  - An introduction to institutional review boards.
AB  - Nurses are conducting their own research studies in many healthcare institutions.
      To conduct research, the researcher will need to gain approval from an
      institutional review board or ethics committee. This article describes the role
      of the institutional review board in clinical research with human subjects.

PMID- 18724184
TI  - The nursing shortage: are we our worst enemy?

PMID- 18724185
TI  - Project Eban: a giant step forward.

PMID- 18724186
TI  - Eban HIV/STD risk reduction intervention: conceptual basis and procedures.
AB  - OBJECTIVE: To describe the Eban HIV/STD Risk Reduction Intervention being
      evaluated in the NIMH Multisite HIV/STD Prevention trial for heterosexual African
      American couples, including the integrated theoretical framework, the structure,
      core elements and procedures of the intervention, and how the content was shaped
      by culturally congruent concepts to address the needs of the study target
      population. DESIGN: The Eban HIV/STD Risk Reduction Intervention is designed to
      address multilevel individual-, interpersonal-, and community-level factors that
      contribute to HIV/STD transmission risk behaviors among heterosexual African
      American couples who are HIV serodiscordant. METHODS: The Eban HIV/STD Risk
      Reduction Intervention employs a mixed modality, couple-based approach that is
      based on an integrated ecological framework incorporating social cognitive theory
      and uses an Afrocentric paradigm that is informed by previous evidence-based
      couples HIV prevention interventions. For this randomized controlled trial,
      African American serodiscordant couples were recruited from 4 urban sites
      (Atlanta, Los Angeles, New York, and Philadelphia) and were randomized to either
      the Eban HIV/STD Risk Reduction Intervention (treatment condition) or a Health
      Promotion Intervention that served as an attentional control condition. Both
      interventions had 4 individual couple sessions and 4 group sessions, but only the
      treatment condition was focused on reducing HIV/STD risk behaviors. Behavioral
      and biological data were collected at baseline, immediately after the
      intervention, and at 6 and 12 months. The theoretical framework, core elements,
      and content of each session are described and lessons learned from this
      intervention trial are discussed. RESULTS: An HIV prevention intervention
      combining couple and group sessions can be feasibly implemented with African
      American HIV-serodiscordant couples who remain at high risk of HIV/STD
      transmission. The lessons learned from the trial suggest that the participants
      responded very well to both the couple and the group sessions. Participant
      feedback suggests that the cultural congruence of the intervention and use of
      African American cofacilitators made them feel comfortable disclosing risky
      behaviors. Participant feedback also suggests that the intervention's couple
      based focus on enhancing dyadic communication and decision-making skills was key
      to helping the couples work together to overcome barriers to using condoms.
      CONCLUSIONS: Participant and facilitator evaluations of the Eban Risk Reduction
      Intervention suggest that couples responded well to the Afrocentric content and
      mixed modalities of the intervention sessions. Couple sessions were optimal for
      enhancing interpersonal and microlevel factors, including communication, problem
      solving, and decision making.

PMID- 18724187
TI  - Eban health promotion intervention: conceptual basis and procedures.
AB  - OBJECTIVE: This article concerns the health promotion intervention that served as
      the comparison condition in Project Eban, the NIMH Multisite HIV/STD Prevention
      Trial for African American Couples. Considerable research has documented the high
      rates of chronic diseases, including heart disease, cancer, stroke, and diabetes,
      among African Americans. Many of these diseases are tied to behavioral risk
      factors-the things that people do or do not do, their diet, the amount of
      exercise they get, and their substance use practices. DESIGN: The Eban Health
      Promotion Intervention was designed to increase healthful behaviors, including
      physical activity, healthful dietary practices, ceasing cigarette smoking and
      alcohol abuse, practicing early detection and screening behaviors, and improving
      medication adherence. As a comparison condition, the Eban Health Promotion
      Intervention was designed to be structurally similar to the Eban HIV/STD Risk
      Reduction Intervention. METHODS: This article describes the intervention and how
      it was developed, integrating social cognitive theory with information collected
      in formative research to ensure that the intervention was appropriate for African
      Americans affected by HIV. CONCLUSION: Project Eban not only tests the efficacy
      of an HIV/STD risk reduction intervention for African American serodiscordant
      couples, but also tests the efficacy of an intervention addressing many of the
      other health problems common in this population.

PMID- 18724188
TI  - Methodological overview of an African American couple-based HIV/STD prevention
      trial.
AB  - OBJECTIVE: To provide an overview of the National Institute of Mental Health
      Multisite HIV/sexually transmitted disease (STD) Prevention Trial for African
      American Couples conducted in 4 urban areas: Atlanta, Los Angeles, New York, and
      Philadelphia. The rationale, study design methods, proposed data analyses, and
      study management are described. DESIGN: This is a 2-arm randomized trial,
      implementing a modified randomized block design, to evaluate the efficacy of a
      couples-based intervention designed for HIV-serodiscordant African American
      couples. METHODS: The study phases consisted of formative work, pilot studies,
      and a randomized clinical trial. The sample is 535 HIV-serodiscordant
      heterosexual African American couples. There are 2 theoretically derived
      behavioral interventions with 8 group and individual sessions: the Eban HIV/STD
      Risk Reduction Intervention (treatment) versus the Eban Health Promotion
      Intervention (control). The treatment intervention was couples based and focused
      on HIV/STD risk reduction whereas the control was individual based and focused on
      health promotion. The 2 study conditions were structurally similar in length and
      types of activities. At baseline, participants completed an audio computer
      assisted self-interview and interviewer-administered questionnaire and provided
      biological specimens to assess for STDs. Similar follow-up assessments were
      conducted immediately after the intervention, at 6 months, and at 12 months.
      RESULTS: The trial results will be analyzed across the 4 sites by randomization
      assignment. Generalized estimating equations and mixed-effects modeling are
      planned to test: (1) the effects of the intervention on STD incidence and condom
      use and on mediator variables of these outcomes and (2) whether the effects of
      the intervention differ depending on key moderator variables (eg, gender of the
      HIV-seropositive partners, length of relationship, psychological distress, sexual
      abuse history, and substance abuse history). CONCLUSIONS: The lessons learned
      from the design and conduct of this clinical trial provide guidelines for future
      couples-based clinical trials in HIV/STD risk reduction and can be generalized to
      other couples-based behavioral interventions.

PMID- 18724189
TI  - Measure of HIV/STD risk-reduction: strategies for enhancing the utility of
      behavioral and biological outcome measures for African American couples.
AB  - OBJECTIVE: Numerous studies have discussed the value of including biological
      outcome measures as a complement to behavioral outcome measures to assess the
      efficacy of HIV risk-reduction interventions. This article highlights strategies
      used to minimize the limitations of including both self-reported sexual behaviors
      and biologically confirmed sexually transmitted diseases as primary outcome
      measures in an HIV/sexually transmitted disease (STD) prevention program for
      African American serodiscordant couples (Eban). DESIGN: Couples receiving an HIV
      intervention condition (Eban) were compared with couples receiving a time
      equivalent General Health Promotion condition on behavioral and biological
      outcomes. Both behavioral and biological data were collected at baseline,
      immediately postintervention, and at 6 and 12 months postintervention. METHODS:
      Literature reviews, consulting other researchers who conducted couples studies,
      our investigative team's experience in previous HIV interventions, and formative
      work were used to develop procedures to minimize potential limitations associated
      with the inclusion of behavioral and biological outcome measures for Eban.
      RESULTS: Given the strengths of including behavioral and biological outcome
      measures, the Eban study chose to have both measures serve as primary outcomes.
      The primary behavioral outcome for the trial is the proportion of protected
      vaginal and anal intercourse episodes that occurred within the index couple in 90
      days before each follow-up assessment and over the 12-month postintervention
      follow-up period. The primary biological outcome is the proportion of
      participants (male or female study partners) with an incident STD (Chlamydia,
      gonorrhea, or trichomoniasis) over the 12-month postintervention follow-up
      period. CONCLUSIONS: Employing procedures to minimize limitations of using self
      reported sexual behaviors and STDs as complementary primary outcomes enhances
      their utility as measures of the efficacy of HIV/STD prevention interventions.

PMID- 18724190
TI  - Formative study to develop the Eban treatment and comparison interventions for
      couples.
AB  - OBJECTIVE: To describe formative and pilot-testing research that generated themes
      and procedures, curricula, and critical measures for a randomized clinical trial
      testing a Risk Reduction Intervention for HIV-serodiscordant African American
      couples (Project Eban). DESIGN: This article describes the themes that emerged
      from discussions with African American serodiscordant couples about HIV-related
      risks from focus groups with 11 couples and pilot study results with 32 couples
      across 4 sites. METHODS: In step 1, focus groups examined the need for a Risk
      Reduction Intervention for HIV-serodiscordant African American couples and
      confirmed 4 themes that formed the basis for the intervention curriculum and
      study format. In step 2, a pilot study refined the clinical trial procedures for
      this population and tested critical measures and selected portions of the
      curriculum for both the treatment and the comparison interventions. RESULTS:
      Based on these findings, stigma and psychological distress, barriers to condom
      use, insufficient support from community and service organizations, and the lack
      of skills that emphasize individual and relationship protection were ultimately
      integrated into the Risk Reduction Intervention. CONCLUSIONS: Pilot study
      findings highlighted the importance of examining gender and ethnicity in HIV
      impacted couples along with factors that heightened HIV-related risk behaviors
      that affect couples' skills and psychological adjustment. The goal was to ensure
      that a skill-based, culturally congruent, relationship-centered intervention
      could be understood and of interest to couples. Future analyses in the main trial
      will be discussed.

PMID- 18724191
TI  - Designing an audio computer-assisted self-interview (ACASI) system in a multisite
      trial: a brief report.
AB  - OBJECTIVE: To describe the advantages and limitations of an audio computer
      assisted self-interview (ACASI) system in a multisite trial with African American
      couples and to present the steps in designing, testing, and implementing a
      system. METHODS: The ACASI system evolved from a paper and pencil interview that
      was pilot tested. Based on this initial work, the paper and pencil interview was
      translated into storyboards that were the basis of the development of ACASI
      system. Storyboards consisted of 1 page per question and provided the programmers
      with the test of the question, valid responses, and any instructions that were to
      be read to the participants. Storyboards were further translated into flow
      diagrams representing each module of the survey and illustrating the skip
      patterns used to navigate a participant through the survey. Provisions were also
      made to insert a face-to-face interview, into the ACASI assessment process, to
      elicit sexual abuse history data, which typically requires specially trained data
      collectors with active listening skills to help participants reframe and
      coordinate times, places and, emotionally difficult memories. RESULTS: The ACASI
      was successfully developed and implemented in the main trial. During an exit
      interview, respondents indicated that they liked using the ACASI and indicating
      that they favored it as the method to answer questions. CONCLUSIONS: It is
      feasible to implement an ACASI system in a multisite study in a timely and
      efficient way.

PMID- 18724192
TI  - Supervision of facilitators in a multisite study: goals, process, and outcomes.
AB  - OBJECTIVE: To describe the aims, implementation, and desired outcomes of
      facilitator supervision for both interventions (treatment and control) in Project
      Eban and to present the Eban Theoretical Framework for Supervision that guided
      the facilitators' supervision. The qualifications and training of supervisors and
      facilitators are also described. DESIGN: This article provides a detailed
      description of supervision in a multisite behavioral intervention trial. The Eban
      Theoretical Framework for Supervision is guided by 3 theories: cognitive behavior
      therapy, the Model of Life-Long Supervision, and the empowerment model of
      culturally responsive supervision. METHODS: Supervision is based on the Eban
      Theoretical Framework for Supervision, which provides guidelines for implementing
      both interventions using goals, process, and outcomes. RESULTS: Because of
      effective supervision, the interventions were implemented with fidelity to the
      protocol and were standard across the multiple sites. CONCLUSIONS: Supervision of
      facilitators is a crucial aspect of multisite intervention research quality
      assurance. It provides them with expert advice, optimizes the effectiveness of
      facilitators, and increases adherence to the protocol across multiple sites.
      Based on the experience in this trial, some of the challenges that arise when
      conducting a multisite randomized control trial and how they can be handled by
      implementing the Eban Theoretical Framework for Supervision are described.

PMID- 18724193
TI  - The role of Community Advisory Boards (CABs) in Project Eban.
AB  - OBJECTIVE: To describe the theoretical principles that guided the establishment
      of Project Eban's Community Advisory Boards (CABs), their functions, and
      composition; the selection and recruitment processes; lessons learned; and
      recommendations on the use of CABs in multisite HIV clinical trial studies.
      METHODS: In the first year of Project Eban's implementation, each of the 4 sites
      formed a local CAB. Member recruitment took place during the first 6 months of
      the study. On average, each site's CAB consisted of 13-19 stakeholders, with a
      total of 62 members for the multisite study, including leaders of HIV/AIDS
      related community-based organizations (CBOs), hospital-based HIV/AIDS service
      providers, HIV/AIDS network leaders in minority communities, CBOs that serve
      predominantly black communities, and consumers. RESULTS: Each of the CAB members
      has expressed a strong commitment to assisting in the conduct of the research.
      CABs are integral to the success of the study, and their input is highly
      respected and used to improve the quality of the research. CONCLUSIONS: This
      article highlights the importance of CABs in the conduct of HIV multisite
      clinical trials and their roles in making the study culturally congruent to meet
      the needs of the black community in dealing with the HIV epidemic.

PMID- 18724194
TI  - Coxa vara in chondrodysplasia: prognosis study of 35 hips in 19 children.
AB  - BACKGROUND: To better understand anatomical and functional outcomes of coxa vara
      in chondrodysplasia according to the initial presenting hip morphology, disease
      type, and impact of surgery. METHODS: Clinical and radiographic records of 19
      children (35 hips) diagnosed with coxa vara and with osteochondrodysplasia were
      reviewed. We classified the hip radiographic findings into 2 groups: (a) group I,
      coxa vara with a fragmented and/or nonossified head; and (b) group II, coxa vara
      with a regular femoral head. Surgical indications in coxa vara included decreased
      range of hip motion (usually diminished abduction, extension, and internal
      rotation), coxa vara with progression documented on regular follow-up hip
      radiographs, and/or severe coxa vara with a Hilgenreiner epiphyseal angle (HEA)
      of 60 degrees or more. Follow-up was until the completion of growth and, for some
      patients, into early adulthood. Mean follow-up was 8 years. RESULTS: Twenty-five
      hips were operated on in 13 patients. In 23 hips, the procedure was a valgus
      osteotomy fixed by pins and wire. A pelvic extension osteotomy without valgus
      osteotomy was performed in one patient (2 hips). Coxa vara recurred in 7 hips. In
      4 of these hips, repeat surgery with hypervalgus osteotomy was indicated to stop
      epiphyseal slipping (3 hips) or to improve the arc of motion (1 hip). Functional
      outcomes were poor in coxa vara associated with poor epiphyseal development
      (nonossified or fragmented epiphysis) as seen in spondyloepiphyseal dysplasia
      congenita, spondyloepimetaphyseal dysplasia, Kniest disease, and multiple
      epiphyseal dysplasia. Coxa vara with physeal instability as observed in
      spondylometaphyseal dysplasia resulted in deformity recurrence postoperatively
      during growth. In contrast, outcome was better in cases of coxa vara with
      nonphyseal/nonepiphyseal involvement, that is, good femoral head morphology,
      stable physis, and good articular cartilage, as seen in cases of metaphyseal
      dysplasia and cleidocranial dysplasia. CONCLUSIONS: Coxa vara with physeal and
      epiphyseal involvement and severe impairment of the articular cartilage has a
      poor prognosis even after reconstructive surgery. In coxa vara with an abnormal
      physis, there were numerous postsurgical recurrences of the deformity during
      growth if the physis was not stabilized at the time of valgus osteotomy. In these
      cases, we should delay osteotomy until an HEA greater than 60 degrees. Coxa vara
      in which only the metaphysis of the femoral neck is involved, the deformity is
      milder and often requires no treatment. Indications for surgery in this group are
      increasing coxa vara, Trendelenburg gait, or an HEA greater than 60 degrees.

PMID- 18724195
TI  - Ligamentum teres tenodesis in medial approach open reduction for developmental
      dislocation of the hip.
AB  - BACKGROUND: When closed reduction of a developmental dislocation of the hip
      fails, some form of open reduction is required. In recent years, the many
      advantages of the medial approach open reduction have been emphasized. However,
      there have been suggestions that the rate of growth disturbance in the proximal
      femur and the requirement for secondary surgical procedures may be higher with
      this route than with others. The purpose of this study was to investigate the
      efficacy and safety of a modified medial approach open reduction, in which the
      stability of the reduction is enhanced by resection of the redundant ligamentum
      teres and suturing of the stump of the tendon to the anteromedial capsule.
      METHODS: The hospital records and radiographs of 92 infants and children with 109
      dislocated hips were reviewed retrospectively. Key demographic and pretreatment
      data were collected by the first author and compared with the outcome at the most
      recent follow-up. In addition, 69 children returned for a clinical evaluation by
      the first author. The outcome at the most recent follow-up was graded according
      to Severin, and associations were sought between pretreatment grade of
      dislocation according to Tonnis, the presence of ossific nucleus, changes in the
      acetabular index, the requirements for secondary surgery, associations with
      previous treatment, and the position of abduction in the postoperative cast.
      RESULTS: At a mean follow-up of 9 years, 89% of hips were classified as Severin
      grade 1 or 2. Avascular necrosis (AVN) was classified according to the system of
      Kalamchi and MacEwen. The incidence of AVN was 41%, but two thirds of these were
      grade 1 (temporary irregular ossification), and the Severin grading in these hips
      was not compromised. The presence of ossification in the capital epiphysis and a
      range of abduction of less than 60 degrees in the hip spica were noted to be
      protective against the development of AVN. Three hips redislocated and required
      additional treatment. Thirty-eight hips required a total of 44 additional
      surgical procedures. CONCLUSIONS: We have demonstrated that it is possible to use
      a medial approach for open reduction of the congenitally dislocated hip in
      combination with tenodesis of the ligamentum teres to the anteromedial joint
      capsule. The incidence of growth disturbance in the proximal femur is high and
      cumulative with long-term follow-up. However, in this large series, the rate of
      hip stability, growth disturbance, and need for secondary surgery are comparable
      to other series. We conclude that the many advantages of open reduction by the
      medial approach outweigh the disadvantages.

PMID- 18724196
TI  - Hip arthrography under general anesthesia to refine the definition of hinge
      abduction in Legg-Calve-Perthes disease.
AB  - BACKGROUND: Hinge abduction is widely accepted as a poor prognostic factor in
      Legg-Calve-Perthes disease (LCPD), whereas the exact definition of hinge
      abduction remains ill defined. The purpose of this diagnostic study was to refine
      the definition of hinge abduction in LCPD using conventional hip arthrography
      under general anesthesia. METHODS: Among 350 hips in 332 LCPD patients, we
      reviewed 92 hips in 90 patients (75 boys and 15 girls) who consecutively
      underwent arthrography under general anesthesia because of an expected poor
      prognosis. The mean age at LCPD onset was 8.2 years (range, 4-13 years). With
      respect to lateral pillar classification, 25 hips were classified as group B, 27
      as B/C border, and 40 as C. Subluxation (>or=3-mm difference from unaffected
      side) was present in 81 (88%) of the 92 hips. The modified Waldenstrom
      classification was used for evaluating the radiographic stage of disease at the
      time of arthrography: 80 hips were classified as fragmentation stage and 12 as
      reossification stage. Hinge abduction was defined as an increased subluxation
      index in maximum abduction and/or a positive impingement sign. RESULTS: Under
      this definition, 11% (10 hips) of the study group had hinge abduction. The range
      of abduction under general anesthesia (40 degrees) was significantly greater than
      in the awake condition (24 degrees, P < 0.0001). CONCLUSIONS: The subluxation
      index and the impingement sign proved to be reliable indicators for diagnosing
      hinge abduction. Conventional arthrography remains useful. General anesthesia
      provided an analgesic effect and muscle relaxation. LEVEL OF EVIDENCE: Level II
      (diagnostic study, development of diagnostic criteria on the basis of consecutive
      patients).

PMID- 18724197
TI  - The outcome of patients with hinge abduction in severe Perthes disease treated by
      shelf acetabuloplasty.
AB  - BACKGROUND: The management of patients with Perthes disease remains
      controversial. In children with hinge abduction and the potential for remodeling,
      we have performed a shelf acetabuloplasty, in an effort to contain the hip and
      allow remodeling. We report our medium-term results in a consecutive series of 27
      children with severe Perthes disease and arthrographically proven hinge
      abduction. This is the first report in the English literature to look
      specifically at the results of treating patients with hinge abduction in severe
      Perthes disease by shelf acetabuloplasty. METHODS: Twenty-seven consecutive
      children with unilateral Perthes disease and arthrographically proven hinge
      abduction were treated with a shelf acetabuloplasty. These patients have been
      prospectively reviewed with a clinical examination and radiographic assessment
      including Catterall, Salter Thompson, and Herring's lateral pillar
      classification. Radiological measurements included percentage acetabular cover,
      medial joint space, and femoral head size ratio. RESULTS: The mean postoperative
      follow-up was 62 months (range, 26-125 months). All patients were Catterall grade
      III or IV and lateral pillar grade B or C and had arthrographically proven hinge
      abduction at the time of surgery. At final follow-up, 14 hips were Stulberg
      grades 1 and 2; 10 hips, grade 3; and 3 hips, grades 4 and 5. The medial joint
      space decreased from a preoperative ratio of 1.9 to 1.4 (P = 0.002), and the
      percentage acetabular cover increased from 81% preoperatively to 97%
      postoperatively (P < 0.001). CONCLUSION: These results suggest overall good
      outcomes from a group of patients with severe Perthes disease as measured by the
      Stulberg grading when compared with historical controls. We suggest that shelf
      acetabuloplasty is a straight forward surgical procedure with good medium-term
      results in patients with severe Perthes disease who have proven hinge abduction
      preoperatively. LEVEL OF EVIDENCE: Level IV case series.

PMID- 18724198
TI  - Guided growth for fixed knee flexion deformity.
AB  - BACKGROUND: Fixed knee flexion deformity (FKFD) is an insidious problem that may
      complicate the management of patients with neuromuscular compromise due to
      cerebral palsy, spina bifida, arthrogryposis, and other conditions. The energy
      costs associated with crouch gait may become prohibitive and, with the inexorable
      progression of fixed knee flexion, secondary pain may ensue as a result of
      fragmentation of the patella and/or tibial tubercle. Concomitant or compensatory
      flexion deformity of the hips and lumbar lordosis may develop, along with "pseudo
      equinus" of the ankles. Recommended treatments for FKFD have included bracing;
      physical therapy; and, in recalcitrant cases, distal femoral osteotomy, posterior
      release, or frame distraction. However, these latter modalities are fraught with
      potential complications including neurovascular damage, loss of fixation,
      undercorrection malunion, fracture, and recurrent deformity. Considering that
      FKFD is often bilateral, the complication risks for a given patient are doubled.
      In a previous study, the senior author reported successful hemiepiphysiodesis of
      the distal anterior femur using staples. However, further experience has
      demonstrated some of the limitations of stapling including relatively slow
      correction and occasional hardware migration. This led to the development of a
      more versatile and reliable solution using a pair of anterior tension band
      plates. METHODS: In this retrospective clinical study, we are reporting this new
      technique of promoting gradual correction through guided growth of the distal
      femur, using a pair of anterior 8-plates. The correction is accomplished
      simultaneously and bilaterally, without immobilization, and may be combined with
      other operative procedures as indicated. We reviewed the charts, radiographs in a
      group of patients treated accordingly. RESULTS: In this group of 18 patients with
      29 deformities, we noted correction averaging 1.3 degrees (range, 0.0 [1 patient]
      4.8 degrees), with minimal complications. No inadvertent coronal plane
      deformities were created. Upon full correction, the plates were removed so as to
      avoid recurvatum. CONCLUSION: As an alternative to posterior capsulotomy or
      supracondylar extension osteotomy, we have found that guided growth is an
      effective and safe method of gradually correcting FKFD in growing children and
      adolescents. LEVEL OF EVIDENCE: 4 (retrospective clinical series).

PMID- 18724199
TI  - Guided growth for pathological physes: radiographic improvement during
      realignment.
AB  - BACKGROUND: Children with rickets are prone to having deformities of the lower
      extremities that are bilateral and often symmetrical. Although initially
      attributed to pathological or "sick" physes, the deformities are eventually seen
      in the metaphyses and diaphyses of the long bones; if left untreated, they may
      result in bone pain and stress fractures. The orthopaedists' role in managing
      these children is to correct and maintain alignment. Alternatively, we have
      exploited the use of hemiepiphysiodesis or guided growth, using staples or, more
      recently, the 8-plate (Orthofix, Verona, Italy). While gradually normalizing the
      mechanical axis, we have noted improvement in the appearance and width of all of
      the ipsilateral physes, not only at the knee but at the hip and ankle as well.
      This report summarizes our observations of the effects on the pathological physes
      in a group of patients with rickets who were preferentially treated with guided
      growth, often starting at a young age. METHOD: This retrospective review approved
      by an institutional review board included 14 children with rickets, including 10
      treated with staples and 4 with 8-plates, who collectively underwent a total of
      68 hemiepiphysiodeses (guided growth) and 35 osteotomies. Each was under
      appropriate medical management during the entire course of treatment, before and
      after surgery. We measured the mechanical axis deviation and anatomic angles of
      the femur and proximal tibia, noting the width and appearance of their physes at
      the hips, knees, and ankles preoperatively and upon correction of the axis.
      RESULTS: Of the 10 stapled patients, we noted 24 (45%) of 53 migrations and 41%
      rebound deformity. Four patients with 15 deformities that corrected with 8-plates
      experienced no hardware migration; for them, it is too early to comment on
      rebound deformity. While gradually correcting the mechanical axis, we have noted
      improvement in the appearance and width, not only of the pan-genu physes but also
      of remote physes at the hip and ankle. We suspect that the improved quality of
      the physes reflects not only the normalization of the mechanical axis but also
      the corresponding resolution of the waddling (varus) or circumduction (valgus)
      gait pattern. CONCLUSION: We recommend early intervention, via guided growth, to
      restore and preserve a neutral axis so that the child can enjoy a normal
      lifestyle while maximizing the growth potential of his or her physes, not only of
      the knees but the hips and ankles as well. We believe that by correcting and
      maintaining alignment, secondary bony deformities may be ameliorated and
      osteotomies for angular correction deferred if not avoided altogether. LEVEL OF
      EVIDENCE: IV (retrospective clinical series).

PMID- 18724200
TI  - Correction of simple and complex pediatric deformities using the Taylor-Spatial
      Frame.
AB  - INTRODUCTION: Correcting multiplanar lower-limb pediatric deformities requires
      complex and, in many cases, staged procedures. The Taylor-Spatial Frame (TSF) is
      a sophisticated external fixator system that can be used to treat simple to
      complex multiplanar and multiapical skeletal deformities. We describe its use in
      53 children during the last 7 years in a variety of pathologies and demonstrate
      its ease of use and versatility. METHODS: A review of medical and physiotherapy
      records, radiographs, and computed tomographic scans of all patients treated with
      a TSF between June 1999 and December 2005 at the Booth Hall Children's Hospital
      was conducted. Data recorded were etiology of deformity, sex, age, number of
      previous operations, preoperative deformity parameters, operative records and
      frame constructs, treatment regime, frame duration, follow-up protocol,
      posttreatment deformity, complications, and clinical and radiological outcome.
      RESULTS: Fifty-three patients between the ages of 12 months and 16 years (mean,
      10.7 years) underwent correction programs for 55 limbs (44 tibia and 11 femurs).
      The etiology of deformity was congenital in 39 cases and acquired in 14. We were
      able to achieve an acceptable correction of deformity (leg length discrepancy <15
      mm, angulation <5 degrees) in 52 limbs. A number of complications were
      encountered, which are discussed. DISCUSSION AND CONCLUSION: We demonstrate its
      ease of use for both surgeon and patient and its versatility in a variety of
      pathologies. The advantages of the TSF system are many. It is a simple frame
      construct, and application is easy. The plan and execution are structured with
      precise end points; it is a single-stage correction and thus avoids frame
      modifications. Any residual deformity can be further corrected by use of the same
      frame. We conclude that the TSF is an effective and efficient way to correct a
      wide variety of simple and complex often obstinate pediatric limb deformities.

PMID- 18724201
TI  - Efficacy and safety of percutaneous epiphysiodesis.
AB  - BACKGROUND: The aims of this study were to evaluate outcomes of percutaneous
      epiphysiodesis, as described by Bowen, in 97 patients and to assess complications
      and determine whether the effect of the epiphysiodesis will accurately follow the
      Moseley chart predictions. METHODS: A total of 97 patients were reviewed
      retrospectively. Fifty-six girls and 41 boys, with a mean skeletal age of 12.6
      years (range, 10-16 years) at the time of operation, were followed up until
      skeletal maturity, a mean of 3.8 years (range, 1-10 years). RESULTS: The mean
      residual leg length discrepancy (LLD) in 88 patients at maturity was 1.3 cm
      (range, 0-3.5 cm). In 9 patients, the epiphysiodesis was combined with a femoral
      lengthening or femoral shortening. The residual leg length discrepancy in these 9
      patients was 3.3 cm at maturity (range, 0-6.5 cm). Minor complications including
      knee effusion (n = 2), superficial wound infection (n = 1), and exostosis (n = 3)
      occurred in 6 patients. Failure of the epiphysiodesis was the only major
      complication seen (n = 3). CONCLUSIONS: This study shows that complications are
      infrequent when performing percutaneous epiphysiodesis and that the Moseley
      straight-line method accurately and efficaciously predicted the timing for
      percutaneous epiphysiodesis in all but one patient who had unpredictable growth
      from hemihypertrophy secondary to a hemangiomatosis.

PMID- 18724202
TI  - Salter-Harris Type III and IV medial malleolar fractures: growth arrest: is it a
      fate? A retrospective study of 48 cases with open reduction.
AB  - Salter-Harris type III and IV medial malleolar fractures (MacFarland fracture) is
      a joint fracture of the ankle in children. The fracture line passes through the
      medial part of the lower epiphyseal disk of the tibia. Prognosis is dominated by
      later risk of misalignment and osteoarthritis. The aim of this study was to
      evaluate the functional and radiological outcome of these fractures. We
      retrospectively analyzed the cases of 48 children with MacFarland fractures (31
      boys and 17 girls), mean age at the time of trauma 11 years 6 months (range, 8-15
      years). The fractures were classed into two groups according to the Salter and
      Harris classification for epiphyseal detachment: Salter III (30 cases) and Salter
      IV (18 cases). Surgical treatment was given in all cases (46 screw fixations, 2
      pin fixations). Three outcome categories were used: good (no pain, no stiffness,
      no limp, no misalignment, no surgical complication, no healing problem), fair
      (pain and/or stiffness and/or limp and/or healing problem without misalignment,
      no surgical complication), and poor (misalignment or surgical complication). Mean
      follow-up was 3 years and 3 months (24-94 months). Twenty-eight children were
      skeletally mature at the longest follow-up. The three-month postoperative
      assessment showed 35 patients with good results and 13 children with fair
      results. Ankle stiffness was noted in 6 cases, ankle pain in 4 cases, wound
      healing complications in 4 cases, limp in 1 case, and snapping in 1 case. The
      long-term outcome was considered good for 45 patients, fair for 2 patients (1
      wound adherence and 1 hypertrophic scar tissue), and poor for 1 patient (6-degree
      varus deformity). We did not note leg-length discrepancy or malunion at the
      longest follow-up. Our results show that growth arrest after MacFarland fracture
      is no fate. We used surgery more than is generally reported by other teams,
      opting for surgery as soon as the displacement was >or=1 mm. Surgical treatment
      was arthrotomy in all cases to achieve anatomical reduction under direct view,
      followed by osteosynthesis. We believe that it is difficult to evaluate if the
      reduction is perfect under the control of the intensifier screen alone.
      Arthrotomy did not lead to ankle stiffness, in any of our patients at longest
      follow-up.

PMID- 18724203
TI  - Inflatable bouncer-related fractures in children.
AB  - BACKGROUND: Inflatable bouncers or moonbouncers are very popular in private and
      public settings and are usually perceived as very safe attractions, but are
      associated with frequent fractures in children. To date, there are no
      publications in the medical literature about these types of injuries. The purpose
      of this study was to show skeletal injuries related to inflatable bouncer use,
      describe their characteristics, and determine possible risk factors and
      preventive measures. METHODS: Demographic data and injury characteristics were
      analyzed for all patients who were treated for inflatable bouncer-associated
      injuries in the pediatric fracture clinic of a level I trauma center from October
      2002 to March 2007. RESULTS: Forty-nine patients were treated for inflatable
      bouncer-related fractures. Children ranged in age from 1.5 to 15 years old (mean
      age, 7.8 years) with a male-female ratio of approximately 3:1. The most commonly
      injured region was the upper extremity (65.5%, n = 32). The most commonly injured
      area was the elbow (31%, n = 15), and the most common single diagnosis was
      supracondylar humerus fracture (22%, n = 11). Diaphyseal long bone fractures were
      found in 18% (n = 9) of the patients and nondiaphyseal in 71% (n = 35). One
      patient (2%) had an open fracture. Mechanisms of injury included collision of 1
      person with another (67%), falling out of a bouncer onto a hard object outside
      the device (19%), and twisting motion to the leg (14%). There was no adult
      supervision in many of the incidents (43%), and the presence of different-aged
      children inside the jumper took place in 52% cases. CONCLUSIONS: Inflatable
      bouncers can cause serious orthopaedic injuries. Children playing in the bouncer
      should be placed in small groups according to their size and should be closely
      supervised at all times. STUDY DESIGN: Case series. Level IV evidence.

PMID- 18724204
TI  - Manipulation of pediatric supracondylar fractures of humerus in prone position
      under general anesthesia.
AB  - BACKGROUND: Displaced pediatric supracondylar fractures are usually treated with
      manipulation and fixation with Kirschner wires. The procedure is commonly
      performed with the patient in supine position. Reducing and stabilizing the
      fracture with the patient in supine position are associated with various risks
      and technical difficulties. METHODS: We describe a technique of manipulative
      reduction and fixation of pediatric supracondylar fractures by positioning the
      patient prone. RESULTS: We have used this technique in 455 patients and prefer it
      to the commonly described method of fracture reduction and stabilization with the
      patient supine. CONCLUSIONS: Positioning the patient prone simplifies the
      reduction and provides adequate exposure to insert Kirschner wires safely from
      both medial and lateral aspects. Positioning the C-arm is easily achieved, and
      good radiographs are obtained without disturbing the reduced fracture. LEVEL OF
      EVIDENCE: Level III.

PMID- 18724205
TI  - Decreased body mass index and restrictive lung disease in congenital thoracic
      scoliosis.
AB  - BACKGROUND: Pediatric patients with congenital thoracic scoliosis often have
      restrictive lung disease and low body weight for age. In other patients with
      respiratory disorders, the work of breathing can increase basal metabolic demands
      and predispose patients to cachexia. The primary study aim was to determine if
      severity of restrictive lung disease, as measured by pulmonary spirometry,
      correlates to decreased body mass index (BMI) in patients with congenital
      thoracic scoliosis. A secondary study aim was to determine what patient factors
      and radiographic measures correlate to low BMI. METHODS: Forty-nine consecutive
      patients with congenital thoracic scoliosis underwent pulmonary function testing,
      spinal radiographs, and BMI percentile for age calculations. Severity of
      restrictive lung disease was quantified by the forced vital capacity percentile
      (FVC%). The BMI percentile for age was also ranked as normal, moderately, or
      markedly decreased (0, <1, or <2 SDs below normal, respectively). The t tests
      were performed between BMI rank and FVC% as well as forced expiratory volume in 1
      second (FEV1). A stepwise multivariate linear regression analysis was performed
      between BMI percentile and FVC%, age, sex, type and extent of previous spine
      fusion, radiographic measures, and pulmonary spirometry measures. RESULTS: The
      mean BMI percentile for all patients was 43% (range, 2%-98%). Both FVC% and FEV1
      percentile were significantly decreased in patients with abnormal BMI (77% vs
      51%, P = 2.78 *10(-1) for FVC%; 75% vs 52%, P = 0.00021 for FEV1 percentile).
      Multivariate analysis showed that FVC% was the only tested variable that
      significantly correlated to BMI percentile. There was a 13.6 times higher risk of
      having an abnormal BMI in patients with moderate to severe restrictive lung
      disease. CONCLUSIONS: Decreased pulmonary function compromise strongly correlates
      to low BMI in patients with congenital thoracic scoliosis. When considering
      moderate to severe restrictive lung disease as defined by FVC%, patients are at
      much higher risk of being significantly underweight. Body mass index is another
      important sign of thoracic insufficiency syndrome in these patients. LEVEL OF
      EVIDENCE: Prognostic case-control study, level III.

PMID- 18724206
TI  - Do adolescents with a severe idiopathic scoliosis have higher locations of the
      conus medullaris than healthy adolescents?
AB  - BACKGROUND: Based on the "uncoupled neuro-osseous growth" theory, the
      hypothesized etiology of adolescent idiopathic scoliosis (AIS), a shorter spinal
      cord or a higher conus location, could be found in AIS patients. However, there
      are no case-control studies with large samples regarding the conus position in
      AIS patients. This study is performed to determine the positions of the conus
      medullaris in AIS patients with a large curve magnitude when compared with
      healthy adolescents and to investigate the relationships of the conus locations
      with patients' age, sex, curve magnitude, and curve pattern. METHODS: Two hundred
      forty AIS patients with a Cobb angle greater than 40 degree were included in this
      study, and 120 age-matched healthy adolescents were recruited to serve as
      controls. Both AIS patients and healthy controls displayed normal on neurological
      examinations. On sagittal magnetic resonance images of the spine in both groups,
      the position on the conus medullaris relative to lumbar vertebrae and
      intervertebral disk space was measured according to a standard method. RESULTS:
      There was no significant difference in the distributions of the positions of the
      conus medullaris in AIS patients and healthy controls (P = 0.448). In both
      groups, the mean position of the conus medullaris was located at the same level,
      which was the lower 1/3 of L1 (range: the middle third of T12 to L2-3 disk
      space). The conus positions were neither significantly different among
      adolescents of different ages (P = 0.662 in AIS and P = 0.897 in controls) nor
      between boys and girls (P = 0.875 in AIS and P = 0.675 in controls). It was shown
      that the conus position was not significantly different among AIS patients with
      different curve severity (F = 0.314, P = 0.731) and curve patterns (F = 0.097, P
      = 0.756). CONCLUSIONS: The mean and the distribution of the conus locations were
      similar for AIS patients and the controls. No significant associations of the
      conus position with curve severity and with curve patterns were found, indicating
      that the conus location might not be involved in the pathogenesis and curve
      progression of AIS. LEVEL OF EVIDENCE: Level III.

PMID- 18724207
TI  - Rectus femoris transfer in children with cerebral palsy: evaluation of transfer
      site and preoperative indicators.
AB  - BACKGROUND: Rectus femoris transfer (RFT) is a treatment option for children with
      cerebral palsy (CP) who exhibit a stiff-knee gait pattern. The rectus femoris
      muscle is transferred to different sites to overcome problems such as tripping
      and falling. Indications for RFT often include preoperative decreased knee range
      of motion (KROM) during swing phase, reduced peak knee flexion in swing (PKFSW),
      abnormal rectus femoris firing patterns on electromyography recordings, and a
      positive Duncan-Ely test. This study investigated the effect of different RFT
      sites on kinematic outcome variables and evaluated the relationship between
      commonly used preoperative surgical indicators and postoperative changes in
      kinematics. METHODS: Thirty-eight patients with CP, who underwent RFT, with
      preoperative and postoperative instrumented gait analyses, were evaluated and
      divided by transfer site: semitendinosus, sartorius, and gracilis. Preoperative
      and postoperative comparisons were made for 5 knee kinematic variables: range of
      motion (KROM), peak flexion at loading response, peak extension at terminal
      stance, PKFSW, and peak extension at terminal swing. Analysis was performed in
      accordance to different transfer sites and overall postoperative change. RESULTS:
      When all limbs were analyzed together for the 5 outcome variables, it was found
      that patients experienced significant (P < 0.05) improvements in sagittal-plane
      kinematics in 3 of the outcome variables: KROM, PKFSW, and peak extension at
      terminal swing. Patients had a significant improvement in postoperative KROM when
      the preoperative KROM was less than 80% of normal. Electromyography pattern and
      Duncan-Ely test were not found to be useful indicators of surgical success.
      CONCLUSION: The authors recommend RFT in children with CP who exhibit a stiff
      knee gait, regardless of transfer site. LEVEL OF EVIDENCE: Level 3.

PMID- 18724208
TI  - Quantitative and qualitative functional evaluation of upper extremity tendon
      transfers in spastic hemiplegia caused by cerebral palsy.
AB  - BACKGROUND: The purpose of this study was to determine if upper extremity
      function and joint positioning improved after tendon transfer surgery in patients
      with spastic hemiplegia caused by cerebral palsy. METHODS: Thirteen patients with
      spastic hemiplegia underwent tendon transfer surgery at a mean age of 10.8 years
      (range, 7-24 years). Before surgery, all patients were evaluated with a
      standardized motion laboratory analysis protocol. At a mean follow-up of 3.6
      years (range, 1-10 years), 13 patients returned for a repeat motion laboratory
      analysis using the same protocol. The motion laboratory studies were then
      compared quantitatively, comparing times for completion of the Jebsen-Taylor hand
      test, and qualitatively for elbow, forearm, wrist, finger, and thumb positions
      using the validated Shriner's Hospital Upper Extremity Evaluation protocol.
      RESULTS: In timed testing on the Jebsen-Taylor hand function test, 5 patients
      improved, 5 patients remained the same, and 3 patients worsened. No statistically
      significant change in timed testing was noted for any of the 6 subtests. A
      qualitative assessment of limb position during completion of tasks showed a
      significant improvement in position for the elbow (P < 0.01), forearm (P < 0.02),
      wrist (P < 0.02), and fingers (P < 0.02). There was no significant change in
      thumb position (P < 0.85). CONCLUSIONS: Tendon transfers, especially for wrist
      extension, can be beneficial in improving upper extremity joint positioning in
      children with spastic hemiplegia. However, significant impairment in hand
      function persists.

PMID- 18724209
TI  - The impact of intrathecal baclofen on the natural history of scoliosis in
      cerebral palsy.
AB  - BACKGROUND: Intrathecal baclofen (ITB) is an effective treatment of spasticity in
      patients with cerebral palsy. However, several recent reports have raised
      concerns that the treatment may be associated with a rapid progression of
      scoliosis. The objective of this study was to further examine the effect of ITB
      treatment on the progression of scoliosis in patients with cerebral palsy.
      METHODS: Spastic cerebral palsy patients who were ITB candidates were followed
      radiographically. Baseline Cobb angles of the primary curve were measured during
      the period of ITB pump insertion and at the most recent follow-up visit. Each
      patient was matched with a control patient by the diagnosis of cerebral palsy,
      age, sex, topographic involvement, and initial Cobb angle. The mean rate of
      change in Cobb angle was compared between ITB and control patients using paired t
      test. A multiple linear regression model was used to examine the difference,
      controlling for age, sex, topographic involvement, and initial Cobb angle.
      RESULTS: Fifty ITB patients and 50 controls were included in the analysis. There
      was no statistically significant difference between the mean change in Cobb angle
      in ITB patients (6.6 degrees per year) compared with the matched control patients
      (5.0 degrees per year, P = 0.39). The results from the multiple regression
      analysis also failed to show a statistically significant difference (0.92 degrees
      per year difference between ITB patients and controls, P = 0.56). CONCLUSIONS:
      The progression of scoliosis in cerebral palsy patients with ITB treatment is not
      significantly different from those without ITB treatment. The findings suggest
      that patients receiving ITB experience a natural progression of scoliosis similar
      to the natural history reported in the literature. LEVEL OF EVIDENCE: Level III.

PMID- 18724210
TI  - Compartment syndrome after hypocalcemic tetany: a case report.
AB  - Compartment syndrome results from pathologically elevated muscle tissue pressure
      within a closed space. It is almost always related to either trauma or
      reperfusion after loss of arterial inflow from occlusion of a major blood vessel.
      We present an unusual case of nontraumatic and nonvascular compartment syndrome
      after hypocalcemia-induced sustained tetany in a 2-year-10-month-old male child
      after a neuroblastoma tumor resection. This particular cause of compartment
      syndrome has been described only once before in an adult patient.

PMID- 18724211
TI  - Analytical radiography of clubfoot after tenotomy.
AB  - The study was undertaken to determine the radiographic impact of the tenotomy
      after the Ponseti method. We report a retrospective and prospective radiographic
      analysis of 37 clubfeet after the Achilles tenotomy. The talocalcaneal angle was
      measured on lateral and anteroposterior views; the tibiotalar and the
      tibiocalcaneal angles were evaluated on the lateral view. The mean age at the
      time the last radiographic analysis was performed was 19 months (range, 13-35
      months). Both studies have the same conclusion: the Achilles tenotomy decreases
      the lateral tibiocalcaneal angle and increases the lateral talocalcaneal angle.
      Furthermore, the tenotomy effect tends to diminish with time. LEVEL OF EVIDENCE:
      therapeutic study, level IV.

PMID- 18724212
TI  - Reliability of the metaphyseal-diaphyseal angle in tibia vara as measured on
      digital images by pediatric orthopaedic surgeons.
AB  - BACKGROUND: Levine and Drennan described the tibial metaphyseal-diaphyseal angle
      (MDA) in an attempt to identify patients with infantile Blount's disease.
      Pediatric orthopaedic surgeons have debated not only the use, but also the
      reliability of this measure. Two techniques have been described to measure the
      MDA. These techniques involved using both the lateral border of the tibial cortex
      and the center of the tibial shaft as the longitudinal axis for radiographic
      measurements. The use of digital images poses another variable in the reliability
      of the MDA as digital images are used more commonly. METHODS: The radiographs of
      21 children (42 limbs) were retrospectively reviewed by 27 staff pediatric
      orthopaedic surgeons. Interobserver reliability was determined using the
      intraclass correlation coefficients (ICCs). Nine duplicate radiographs (18
      duplicate limbs) that appeared in the data set were used to calculate ICCs
      representing the intraobserver reliability. A scatter plot was created comparing
      the mean MDA determined by the 2 methods. The strength of a linear relationship
      between the 2 methods was measured with the Pearson correlation coefficient.
      Finally, we tested for a difference in variability between the 2 measures at
      angles of 11 degrees or less and greater than 11 degrees by comparing the
      variance ratios using the F test. RESULTS: The interobserver reliability was
      calculated using the ICC as 0.821 for the single-measure method and 0.992 for the
      average-measure method. The intraobserver reliability was similarly calculated
      using the ICC as 0.886 for the single-measure method and 0.940 for the average
      measure method. Pearson correlation coefficient (0.9848) revealed a highly linear
      relationship between the 2 methods (P = 0.00001). We also found that there was no
      statistically significant variability between the 2 methods of calculating the
      MDA at angles of 11 degrees or less compared with angles greater than 11 degrees
      (P = 0.596688). CONCLUSIONS: There was excellent interobserver reliability and
      intraobserver reliability among reviewers. Using either the lateral diaphyseal
      line or center diaphyseal line produces reasonable reliability with no
      significant variability at angles of 11 degrees or less or greater than 11
      degrees. LEVEL OF EVIDENCE: Level IV.

PMID- 18724213
TI  - The international registry on hand and composite tissue transplantation.
AB  - BACKGROUND: Since May 2002, all groups performing hand transplantations have
      supplied information to the International Registry on Hand and Composite Tissue
      Transplantation (IRHCCT). The analysis of all cases with follow-up information up
      to September 2007 is presented here. METHODS: From September 1998 to September
      2007, 38 hands (18 unilateral and 10 bilateral hand transplantations) and two
      digits have been reported to IRHCTT, for a total of 30 patients with a follow-up
      period ranging from 6 months to 9 years. They were 28 males and two females,
      median age of 34 years. Time since hand loss ranged from 2 months to 34 years and
      in 50% of cases the level of amputation was at wrist level. Immunosuppressive
      therapy included tacrolimus, mycophenolate mofetil, rapamycin, and steroids;
      polyclonal or monoclonal antibodies were used for induction. Topical
      immunosuppression was also employed in several cases. RESULTS: Patient survival
      was 100%. Graft survival was 100% at 1 and 2 years. Except for the Chinese
      patients, current graft survival is 95.6% and cause of graft loss was always no
      compliance to the treatment. Acute rejection episodes occurred in 85% of the
      patients within the first year and they were reversible in all compliant
      patients. Side-effects included opportunistic infections and metabolic
      complications. All patients developed protective sensibility, 90% of them
      developed tactile sensibility, and 72% also a discriminative sensibility. Motor
      recovery enabled patients to perform most daily activities. CONCLUSIONS: Hand
      transplantation is feasible with a high success rate and satisfactory functional
      outcome.

PMID- 18724214
TI  - Split-liver transplantation: an underused resource in liver transplantation.
AB  - Split-liver transplantation is an efficient tool to increase the number of liver
      grafts available for transplantation. More than 15 years after its introduction
      only the classical splitting technique has reached broad application.
      Consequently children are benefiting most from this possibility. Full-right full
      left splitting for two adult recipients has been shown to work but is hampered
      mainly by the dangers of small-for-size transplantation. A solution to this last
      problem would completely change the scope of split-liver transplantation. Organ
      allocation systems and collaboration between centers play a crucial role in the
      chances to let suitable patients profit from this valuable source of extra
      grafts.

PMID- 18724215
TI  - Incentives for living kidney donation: what does the public think?
AB  - This mini-review describes a number of recent surveys that have been performed to
      study public opinion on the idea of introducing incentives for living kidney
      donation. The results of these surveys are comparable: about a quarter of the
      population is in favor of this idea, whereas the majority is opposed or
      undecided.

PMID- 18724216
TI  - Utilization and outcomes of kidney paired donation in the United States.
AB  - BACKGROUND: Kidney paired donation (KPD) offers the best transplant option for
      patients with incompatible live kidney donors. Although studies suggest
      substantial expansion of the donor pool if fully used, few patients in the United
      States have undergone KPD. METHODS: We analyzed the 209 KPD and 89 list paired
      donation (LPD) transplants reported to United Network for Organ Sharing to better
      understand access to these modalities, clinical outcomes, and areas of potential
      expansion. RESULTS: Although many centers offer KPD/LPD, most centers have
      performed no more than a handful of transplants. As expected, outcomes with
      KPD/LPD were equivalent to direct donation matched controls. In analyzing current
      practice, we identified two limitations to KPD in its current use. First, KPD is
      likely limited now by benefiting mostly patients who are easy to identify and
      match (such as A donors with B recipients or B donors with A recipients). Second,
      although some expansion of local KPD availability has reduced travel requirements
      for patients in those areas, significant room for growth remains. CONCLUSIONS:
      Our results suggest that full utilization of KPD would encourage registration of
      and improve matching for patients who are more difficult to identify and match
      (such as highly sensitized recipients). Furthermore, expansion of KPD would
      likely reduce travel requirements and thereby improve access to this treatment
      modality.

PMID- 18724217
TI  - Ingredients for a successful living donor kidney exchange program.

PMID- 18724218
TI  - Getting the measure of renal function: determination of best predicted creatinine
      in living-donor kidney renal transplant recipients based on donor kidney
      function.

PMID- 18724219
TI  - Lung transplantation for lymphangioleiomyomatosis: the French experience.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare disease, leading in some
      cases to end-stage respiratory failure. Lung transplantation (LT) represents a
      therapeutic option in advanced pulmonary LAM. METHODS: We conducted a
      retrospective multicenter study of 44 patients who underwent LT for LAM at 9
      centers in France between 1988 and 2006. RESULTS: All patients were women with a
      mean age of 41+/-10 years at LT. There were 34 single-lung transplants and 11
      bilateral transplants (one retransplantation). Prior clinical events related to
      LAM were present in 75% of the patients and previous thoracic surgical procedures
      were noted in 86.6% of cases. At the latest preoperative evaluation, 30 patients
      had an obstructive pattern (mean forced expiratory volume in 1 second: 26%+/-14%
      of predicted) and 15 had a combined restrictive and obstructive pattern, with a
      mean KCO=27%+/-8.8% of predicted, PaO2=52.8+/-10.4 and PaCO2=42.6+/-9.8 mm Hg.
      Intraoperative cardiopulmonary bypass was required in 13 cases. The length of
      mechanical ventilation was 7.5+/-12.8 days. The median duration of follow-up was
      37 months. The 1, 2, 5, and 10 years survival rates were 79.6%, 74.4%, 64.7%, and
      52.4%, respectively. Extensive pleural adhesions were found in 21 patients
      leading to severe intraoperative hemorrhage. Postoperative LAM-related
      complications were pneumothorax in the native lung in five patients, chylothorax
      in six, bronchial dehiscence or stenosis in seven. There were two cases of
      recurrence of LAM. CONCLUSION: Despite a high morbidity mainly caused by previous
      surgical interventions and disease-related complications, LT is a satisfactory
      therapeutic option for end-stage respiratory failure in LAM.

PMID- 18724220
TI  - Epidemiology of BK virus in renal allograft recipients: independent risk factors
      for BK virus replication.
AB  - BACKGROUND: Identification of risk factors for BK virus (BKV) replication may
      improve transplant outcome. We investigated the impact of immunosuppressive drugs
      on the prevalence of BKV replication in recipients of human renal allografts.
      METHODS: One hundred twenty renal allograft recipients were studied prospectively
      at 1, 3, and 6 months posttransplantation to identify risk factors for BKV
      replication. BKV replication was quantified by measurement of urinary cell BKV
      VP1 mRNA levels using BKV specific primers and TaqMan probe in a real-time
      quantitative polymerase chain reaction assay. Levels of urinary cell mRNA for
      granzyme B, CD103, and transforming growth factor-beta1 were measured to
      ascertain whether BKV replication is associated with an inflammatory signature.
      RESULTS: The prevalence of BKV replication increased over time and was highest at
      6 months compared with 1 or 3 months posttransplantation (P<0.001). A logistic
      regression model analysis demonstrated that steroid maintenance therapy (odds
      ratio: 8.3, P=0.003) and induction with rabbit anti-human thymocyte globulin
      (odds ratio: 5.8, P=0.008) were independent risk factors for BKV replication.
      Neither mycophenolate mofetil dose nor tacrolimus dose or trough levels were
      different between those with or without BKV replication. The development of acute
      rejection or antirejection treatment with methylprednisolone did not increase the
      risk of BKV replication. BKV replication was associated with heightened levels of
      urinary cell mRNA for granzyme B (P<0.002), CD103 (P<0.005) but not for
      transforming growth factor-beta1 (P>0.05). CONCLUSIONS: Steroid maintenance
      therapy and induction with antithymocyte globulin are independent risk factors
      for BKV replication in renal allograft recipients treated with tacrolimus and
      mycophenolate mofetil.

PMID- 18724221
TI  - Preferential benefit of antibody induction therapy in kidney recipients with high
      pretransplant frequencies of donor-reactive interferon-gamma enzyme-linked
      immunosorbent spots.
AB  - BACKGROUND: The decision to use induction antibody therapy in kidney
      transplantation is often based on perceived patient risk, as no objective
      biomarker has been shown to predict the effectiveness of such therapy. Because
      pretransplant T-cell alloreactivity has been shown to increase the risk of poor
      posttransplant outcome, and because induction therapy is directed at alloreactive
      T cells, we hypothesized that antibody induction would preferentially benefit
      patients with high pretransplant antidonor T-cell immunity. METHODS: In a
      retrospective analysis of 130 patients who had enrolled in an immune monitoring
      study, we correlated acute rejection rates, renal allograft function, and use of
      antibody induction therapy with donor-reactive interferon-gamma enzyme-linked
      immunosorbent spot (ELISPOT) frequencies assessed pre and postkidney
      transplantation. RESULTS: Of the 32 ELISPOT (+) patients, eight received
      induction therapy and had no rejection. Of the remaining 24 ELISPOT (+) patients
      with no induction therapy, acute rejection occurred in 11 (46%), (P=0.02). Twelve
      month glomerular filtration rate was significantly higher in the eight patients
      who received induction therapy (P=0.0001). Posttransplant conversion to a
      negative ELISPOT assay occurred in 86% of patients who received induction therapy
      vs. 35% of patients who did not (P=0.02). In the ELISPOT (-) cohort, acute
      rejection rates ( approximately 15%) and glomerular filtration rates were similar
      in the 98 patients regardless of induction therapy. CONCLUSIONS: Our results
      suggest that antibody induction therapy preferentially benefits kidney transplant
      candidates with strong pretransplant donor-reactive cellular immunity. If
      confirmed prospectively, pretransplant ELISPOT assessments could be used to guide
      decision making regarding induction therapy.

PMID- 18724222
TI  - Non-melanoma skin cancer incidence and risk factors after kidney transplantation:
      a Canadian experience.
AB  - BACKGROUND: Non-melanoma skin cancer (NMSC) after kidney transplantation is
      common and can result in significant morbidity and mortality. Incidence and risk
      factors for NMSC can vary between geographic locations and there is no literature
      describing the incidence or risk factors for NMSC in Canada. METHODS: The purpose
      of this retrospective cohort study was to determine the incidence of NMSC, the
      time of development of NMSC, and risk factors (including sun exposure history)
      for NMSC in kidney transplant recipients between 1990 and 2003 in our center
      (n=926). RESULTS: We observed a 9.7% incidence of NMSC lesions after kidney
      transplant with a median time of development of a first NMSC lesion of 4 years.
      Risk factors for NMSC (multivariate analysis) include older men (>45 years), a
      history of posttransplant warts, and longer duration of residence in a northern
      climate. CONCLUSION: We conclude that NMSC is common after kidney transplantation
      in a northern climate and these individuals require disease prevention-specific
      education, more vigilant surveillance and early referral and treatment.

PMID- 18724223
TI  - The importance of cold and warm cardiac ischemia for survival after heart
      transplantation.
AB  - BACKGROUND: Ischemia time is a risk factor for mortality after heart
      transplantation that can be influenced by organizational factors such as
      transport arrangements and organ allocation. METHODS: We used the United Kingdom
      Cardiothoracic Transplant Audit database to analyze the outcome of 1491 first
      isolated orthotopic adult heart transplants performed between April 1995 and
      March 2004. Ischemia time and its components (transport time and surgical implant
      time) were related to 30-day mortality using a multivariable logistic regression
      model. RESULTS: The median total ischemia time increased from 171 min
      (interquartile range: 149-198) to 213 min (interquartile range: 181-256) during
      the study period (P<0.0001). This was due to an increase in transport times that
      was partly explained by increased organ exchange between centers and also because
      of an increase in surgical implant times. Thirty-day survival decreased over the
      study period (91%-84%) with some evidence of a linear trend towards decreasing
      survival over time (P=0.089). After correcting for other known risk factors, the
      odds ratio of death within 30 days associated with each 15 min increment in
      transport time was 1.06 (95% confidence interval: 1.01-1.12) and with each 15 min
      increment in surgical implant time was 1.11 (95% confidence interval: 1.04-1.18).
      CONCLUSION: Both transport and implant times were directly related to 30-day
      mortality after heart transplantation. Ischemia time should be considered in
      organ allocation and controlled during the heart transplant procedure.

PMID- 18724224
TI  - Reduction in erythropoietin resistance after conversion from sirolimus to enteric
      coated mycophenolate sodium.
AB  - BACKGROUND: Anemia is a known adverse effect of sirolimus (SRL) therapy.
      Sirolimus may contribute to anemia by a direct antiproliferative effect or by
      increasing inflammation, worsening kidney function, or decreasing iron
      utilization. After observing the need for high dose exogenous erythropoietin
      dosage in some patients on SRL, we hypothesized that SRL therapy may influence
      anemia by inducing a state of erythropoietin resistance. METHODS: Twenty-five
      stable renal transplant patients on maintenance tacrolimus and SRL therapy were
      enrolled in a prospective trial with conversion from SRL to enteric coated
      mycophenolate sodium. Measurement of plasma erythropoietin and red cell indices
      were performed pre- and postconversion. RESULTS: Renal function remained
      unchanged after conversion. Serum hemoglobin (Hb) increased in 18/21 (86%) of
      patients after conversion. Endogenous erythropoietin level decreased from a
      median of 28.3 (11.5-374) to 16.6 (3.1-78.8) mIU/mL, (P<0.001); and the
      erythropoietin:Hb ratio dropped from 2.7 (0.7-34.3) to 1.2 (0.2-6.7), (P<0.001);
      indicating less erythropoietin resistance after conversion. Mean corpuscular
      volume increased after conversion, but transferrin saturation and ferritin did
      not change. Conversion was complicated by posttransplant erythrocytosis in two
      patients. DISCUSSION: Conversion from SRL to enteric coated mycophenolate sodium
      led to an increase in Hb and a decrease in erythropoietin resistance in stable
      kidney transplant recipients. Increase in Hb seemed to be independent of renal
      functional changes or changes in iron sequestration.

PMID- 18724225
TI  - Parathyroidectomy followed by kidney transplantation can improve bone mineral
      density in patients with secondary hyperparathyroidism.
AB  - BACKGROUND: We studied bone mineral density (BMD) after total parathyroidectomy
      plus autotransplantation (TPTD plus AT) followed by kidney transplantation in
      patients with symptomatic secondary hyperparathyroidism. METHODS: We recruited 43
      patients who were operated on with TPTD plus AT for this study. Group A (n=36)
      patients continued hemodialysis regularly thereafter; Group B (n=7) patients were
      followed by cadaveric kidney transplantation. In group A, serum calcium,
      phosphorus, alkaline phosphatase (Alk-ptase) and intact parathyroid hormone
      (iPTH) levels were measured at baseline, 1 week, and in the late follow-up
      period. In group B, serum calcium, phosphorus, Alk-ptase and iPTH levels were
      measured at baseline, 1 week after parathyroidectomy, and in the late follow-up
      period after kidney transplantation. The BMD of lumbar spine, femur, ulna and
      radius was measured with dual x-ray absorptiometry at baseline, and again at 1
      year in group A and at 1 year after kidney transplantation in group B. RESULTS:
      At 1 week after TPTD plus AT, calcium, phosphorus, and iPTH levels decreased
      significantly but Alk-ptase did not. In the late follow up period calcium,
      phosphorus, Alk-ptase and iPTH levels decreased significantly compared with those
      at baseline. In group A, the BMD of lumbar spine, femur, ulna and radius
      increased significantly 1 year later. In group B, the BMD of femur, ulna and
      radius increased significantly 1 year after kidney transplantation, but the BMD
      of lumbar spine did not. CONCLUSION: TPTD plus AT followed by kidney
      transplantation performed for symptomatic secondary hyperparathyroidism can
      improve the BMD of femur, ulna, and radius.

PMID- 18724226
TI  - Determination of lowest possible creatinine in living-donor kidney renal
      transplant recipients based on donor kidney function.
AB  - BACKGROUND: The objective of this study was to use information from a donor to
      establish the lowest possible serum creatinine (SCr) of the recipient as a means
      of identifying early graft dysfunction. METHODS: We analyzed retrospectively 58
      pairs of living donors and recipients. The lowest possible SCr was calculated
      from four different formulae derived from Cockcroft-Gault formula: Ax(140
      recipient age)xrecipient weight/donor GFR (A, women: 1.04, men: 1.23). Donor GFR
      was represented by the following values (a) mSCrD0: measured pretransplant GFR
      for both kidneys, (b) mSCrSKD0: single transplanted kidney GFR on day 0, (c)
      eSCrD0: estimated GFR based on SCr at day 0, or (d) eSCrD30: on day 30. These
      resulting estimated SCr were tested for correlation coefficient, bias, precision,
      and accuracy in predicting the lowest observed recipient SCr during the first
      year posttransplant. RESULTS: The lowest possible SCr was 80+/-22 micromol/L for
      mSCrD0, 79.1+/-23 micromol/L for mSCrSKD0, 83+/-27 micromol/L for eSCrD0, and
      115+/-22 micromol/L for eSCrD30. Mean values for lowest possible SCr correlated
      significantly with the lowest observed SCr for all four formulae. The eSCrD0
      formula showed the best correlation (r=0.47), the smallest positive bias (20.5
      micromol/L), the highest precision (21.9 micromol/L), and the second highest
      percentage of predicted values that fell within 30% of the observed SCr (69%).
      CONCLUSION: The use of the Cockcroft-Gault derived formula with eSCrD0 may be a
      useful tool to detect early discrepancy between observed and lowest possible SCr
      value. This could help to identify patients who may require invasive
      investigations.

PMID- 18724227
TI  - The impact of hemoglobin levels on patient and graft survival in renal transplant
      recipients.
AB  - BACKGROUND: It remains unclear whether low hemoglobin levels are associated with
      increased mortality or graft loss after renal transplantation. This study
      assessed the relationship of hemoglobin levels with patient and graft survival in
      3859 patients with functioning renal transplants more than 6-months
      posttransplantation. METHODS: Detailed data was prospectively collected as part
      of the pharmacovigilance Long Term Efficacy and Safety Surveillance project.
      RESULTS: Lower hemoglobin levels were associated with graft loss on multivariate
      analysis adjusted for demographic characteristics, comorbidity, and biochemical
      variables; lower hemoglobin was associated with mortality on univariate, but not
      adjusted analysis; hemoglobin variability was associated with mortality and graft
      loss on univariate, but not multivariate analysis. Older recipient age, lower
      serum albumin, raised urea, increased comorbidity (Charlson Index), and
      angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker
      (ARB) non-use were also associated with mortality. Younger recipients, male
      recipients and those with lower serum albumin, lower body mass index, higher
      systolic blood pressure, and impaired allograft function experienced higher graft
      failure rates. CONCLUSIONS: This study suggests that full correction of
      hemoglobin levels to improve mortality in renal transplant recipients is
      unjustified; further study is required to assess the effect of hemoglobin
      correction in delaying graft failure. It also highlights other nonimmunologic
      risk factors for adverse outcomes in renal transplant recipients.

PMID- 18724228
TI  - Infiltration of nestin-expressing cells in interstitial fibrosis in chronic
      cyclosporine nephropathy.
AB  - BACKGROUND: Nestin-expressing cells play a role in the repair process of injured
      tissues and organs. This study examined the nestin-expressing cells in
      interstitial fibrosis in experimental chronic cyclosporine A (CsA) nephropathy.
      METHODS: Sprague Dawley rats were treated daily for 1 or 4 weeks with CsA (15
      mg/kg) or vehicle (VH; olive oil, 1 mg/kg). Nestin mRNA expression was evaluated
      with reverse transcriptional-polymerase chain reaction, and nestin-expressing
      cells were detected immunohistochemically. Localization of nestin was performed
      with double labeling studies for vimentin, aquaporin 1, or calbindin D28K.
      RESULTS: Nestin mRNA expression was not different between VH- and CsA-treated rat
      kidneys. Nestin-expressing cells were rarely observed in the cortex in the VH
      group, but CsA-induced renal injury caused an increase in nestin-expressing cells
      in the cortex in a time-dependent manner. Nestin-expressing cells in the CsA
      group were localized to the area of interstitial fibrosis, and the number of
      nestin-expressing cells well correlated with the score of interstitial fibrosis
      (r=0.898). Nestin-expressing cells did not express vimentin, aquaporin 1, or
      calbindin D28K. CONCLUSIONS: CsA-induced renal injury recruits nestin-expressing
      cells to injured areas, and these cells might be involved in reparative fibrosis
      in the progression of chronic CsA nephropathy.

PMID- 18724229
TI  - Interferon-gamma conditioning ex vivo generates CD25+CD62L+Foxp3+ regulatory T
      cells that prevent allograft rejection: potential avenues for cellular therapy.
AB  - BACKGROUND: Regulatory T cells (Treg) play important roles in preventing
      autoimmunity, graft-versus host disease and transplant rejection. In rodent
      transplant models, tolerance induction strategies can induce graft protective
      CD25CD4 Treg in vivo but therapeutic exploitation of active regulation will more
      likely depend on protocols that allow generation or selection of regulatory cells
      ex vivo for use as a cellular therapy. We have used adoptive transfer skin and
      islet allograft models to identify, develop and evaluate ex vivo protocols that
      generate donor-reactive, adaptive Treg. METHODS: Naive CDA CD4 T cells were
      stimulated with allogeneic antigen-presenting cell under neutral conditions or
      with cytokine modification, restimulated under identical conditions and
      subsequently analyzed for cytokine profile, phenotypic markers characteristic of
      Treg and in vivo regulatory function. RESULTS: Without modification, CD4 T cells
      default to a Th2 phenotype characterized by a dominant interleukin-4 response
      which is profoundly detrimental to allograft survival. However, addition of
      exogenous interferon-gamma suppresses interleukin-4 production without priming
      for effector function, induces suppressor of cytokine signaling-1 and results in
      up-regulation of Foxp3 and CD62L. The generation of these populations is enhanced
      by, but is independent of, the presence of naturally occurring endogenous Treg.
      Most importantly, when tested for regulatory function in vivo, these cells
      prevent rejection of both skin and islet allografts mediated by effector T cells.
      CONCLUSIONS: These data reveal an unexpected role for interferon-gamma in the
      generation of Treg ex vivo and suggest a possible route for the generation of
      regulatory cells for therapeutic use.

PMID- 18724230
TI  - Increased transplant arteriosclerosis in the absence of CCR7 is associated with
      reduced expression of Foxp3.
AB  - BACKGROUND: The chemokine receptor CCR7 plays a pivotal role in the homing of
      naive T cells and regulatory T cells to secondary lymphoid organs and the
      migration of dendritic cells into afferent lymphatic vessels. Antigen
      presentation, T cell recruitment, and expansion of regulatory cells are crucial
      events in establishing and controlling chronic allograft dysfunction. In this
      study, we report an important role for chemokine receptor CCR7 in the development
      of transplant arteriosclerosis. METHODS: Fully major histocompatibility complex
      mismatched CBA (H2) donor aortas were transplanted into BALB/c-CCR7 (H2), BALB/c
      CCR7 (H2), or BALB/c-CCR7 (H2) recipients. Grafts were analyzed by histology,
      morphometry, and immunofluorescence on day 30 after transplantation. Intragraft
      cytokine mRNA production was analyzed by realtime polymerase chain reaction on
      day 14 after transplantation. RESULTS: After implanting fully major
      histocompatibility complex-mismatched donor aortas into CCR7-deficient
      recipients, transplant arteriosclerosis was significantly elevated. CD4 depletion
      resulted in a reduction of intima proliferation in CCR7 recipients whereas CD8
      depletion had no effect. Analysis of aortic grafts from CCR7 recipients revealed
      high numbers of infiltrating CD4, F4/80, and CD205 cells. Furthermore, intragraft
      cytokine production showed higher levels of interleukin-4, interleukin-12, and
      eotaxin mRNA expression, whereas significantly lower Foxp3 mRNA expression was
      observed in CCR7 recipients. CONCLUSION: These data suggest that although
      alloantigen presentation in secondary lymphoid organs is hampered in CCR7
      deficient recipients, this process may take place within the allograft itself,
      leading to increased formation of transplant arteriosclerosis. The decrease in
      Foxp3 expression despite increased in CD4 T cell infiltration indicates a
      reduction in T regulatory cells possibly influencing the intensity of the graft
      rejection.

PMID- 18724231
TI  - Comparison of human T cell repertoire generated in xenogeneic porcine and human
      thymus grafts.
AB  - BACKGROUND: Xenogeneic thymus transplantation is an effective approach to
      achieving T cell tolerance across highly disparate xenogeneic species barriers.
      We have previously demonstrated that phenotypically normal, specifically tolerant
      human T cells are generated in porcine thymic grafts. In this study, we assessed
      the diversity of the human T cell repertoire generated in porcine thymic
      xenografts. We also examined the ability of porcine thymus grafts to coexist with
      human thymus grafts. METHODS: Fetal swine (SW) or human (HU) thymus with human
      fetal liver fragments were transplanted under the kidney capsule of 3Gy
      irradiated NOD/SCID mouse recipients. Thymus tissue was harvested approximately
      16 weeks posttransplant for analysis of mixed lymphocyte reactions and
      spectratyping of human CD4 and CD8 single positive thymocytes. RESULTS: T cell
      receptor beta genes of human CD4 and CD8 single positive cells developing in HU
      and SW thymus grafts showed similar, normal CDR3 length distributions. Human T
      cells developing in SW thymus grafts showed specific unresponsiveness to the
      major histocompatibility complex of the donor swine in mixed leukocyte reaction
      assays. In two of three animals receiving SW and HU thymus grafts under opposite
      kidney capsules, both grafts functioned. In animals with surviving SW grafts,
      thymocytes from the SW but not the HU grafts showed specific unresponsiveness to
      the SW donor. CONCLUSION: Swine thymus grafts support generation of human T cells
      with a diverse T cell receptor repertoire. Human thymocytes in human thymus
      grafts are not tolerized by the presence of an additional porcine thymus, but
      tolerance might be achieved by postthymic encounter with porcine antigens.

PMID- 18724232
TI  - Entecavir therapy for adefovir-resistant hepatitis B virus infection in kidney
      and liver allograft recipients.
AB  - The aim of our study was to assess the efficacy and safety of entecavir in kidney
      and liver-transplant recipients with chronic hepatitis B virus (HBV) infection.
      Ten male transplant patients with chronic HBV infection (eight kidney- and two
      liver-transplant patients), who have become adefovir (n=9) or lamivudine
      resistant (n=1) were given entecavir at 0.5 to 1 mg/d. All patients were HBs Ag
      positive: six were HBe Ag(-)/HBe Ab(+), and four were HBe Ag(+)/HBe Ab(-). After
      a median follow-up of 16.5 months, entecavir therapy was associated with a
      significant decrease in HBV DNA viral load, that is, 3.86 (2.71-6.46) log10
      copies/mL at baseline down to 2.94 (2.15-4) log10 copies/mL at last follow-up
      (P=0.004). Rate of HBV DNA clearance was 50% in both HBeAg(+) and HBeAg(-)
      patients. There were no significant changes in renal function or hematological
      parameters. This study demonstrates that entecavir therapy is safe and efficient
      in HBV(+) organ-transplant patients.

PMID- 18724233
TI  - Limited efficacy and unacceptable toxicity of cyclophosphamide for the induction
      of mixed chimerism and renal allograft tolerance in cynomolgus monkeys.
AB  - To induce mixed chimerism and renal allograft tolerance in cynomolgus monkeys,
      cyclophosphamide (CP) and total body irradiation (TBI) were compared as part of a
      nonmyeloablative conditioning regimen. CP induced dose-dependent neutropenia and
      lymphopenia, but hematopoietic recovery was more rapid than that observed in the
      TBI group. Absolute B cell counts after CP were significantly higher (P<0.01)
      than those in the TBI group. With CP, a total dose of 200 mg/kg with CD154
      blockade regularly induced multilineage chimerism. Nevertheless, the recipients
      failed to achieve long-term survival because of rejection (3 of 5),
      posttransplantation B cell lymphoma (1 of 5), and toxicities of CP (1 of 5). As
      previously reported, 3 Gy of TBI with either splenectomy or CD154 blockade
      induced mixed chimerism and renal allograft tolerance, with significantly less
      morbidity and mortality than that produced by CP. Thus, TBI is more effective and
      less toxic than CP as part of a nonmyeloablative regimen for the induction of
      mixed chimerism and renal allograft tolerance in cynomolgus monkeys.

PMID- 18724234
TI  - Improved renal function, with similar proteinuria, after two years of early
      tacrolimus withdrawal from a regimen of sirolimus plus tacrolimus.
AB  - Results at 1 year of a pilot randomized trial with 87 kidney graft recipients,
      comparing the maintenance treatment with sirolimus, tacrolimus and steroids
      (group I) versus tacrolimus withdrawal since the third month onward, followed by
      maintenance with SRL and steroids (group II) have shown that early elimination of
      tacrolimus may result in improved renal function and blood pressure control. At 2
      years, 26 and 25 patients in groups I and II, respectively, were analyzed in an
      on-therapy and an ITT analysis. In the on-therapy analysis, group II showed lower
      serum creatinine (1.3+/-0.2 vs. 1.6+/-0.6 mg/dL) and lower diastolic blood
      pressure (74+/-9 vs. 80+/-11 mm Hg). No acute rejections occurred during the
      second year of follow-up. In more than 90% of patients, proteinuria was less than
      1 g/d, and in 50% it was negative. In the ITT analysis, differences were found
      only in diastolic blood pressure (80+/-10 vs. 74+/-8 mm Hg in groups I and II
      respectively, P=0.009). Tacrolimus withdrawal from a combination of sirolimus and
      tacrolimus, in selected patients, may be observed at 2 years by an improvement in
      renal function and blood pressure without a higher incidence of proteinuria.

PMID- 18724235
TI  - Common iliac artery lying posterior to psoas major identified during kidney
      transplantation.

PMID- 18724236
TI  - De novo or persistent pseudomonal airway colonization after lung transplantation:
      importance for bronchiolitis obliterans syndrome?

PMID- 18724239
TI  - Intramucosal poorly differentiated colorectal carcinoma: can it be managed
      conservatively?

PMID- 18724240
TI  - Esophageal polypoid dysplasia of gastric foveolar phenotype with focal
      intramucosal carcinoma associated with Barrett's esophagus.
AB  - We describe a rare case of esophageal polypoid dysplasia with gastric phenotype
      and focal intramucosal carcinoma associated with Barrett's esophagus. A 69-year
      old man with a long history of gastroesophageal reflux disease was initially seen
      at an outside institution for evaluation of significant dysphagia. Screening
      upper gastrointestinal endoscopic evaluation revealed a large intraluminal
      polypoid lesion occluding the distal portion of the esophagus. Surgery was
      performed with resection of the distal esophagus and proximal stomach. The
      histopathologic examination of this lesion revealed an exuberant polypoid gastric
      epithelium with areas of low-grade dysplasia, high-grade dysplasia, and focal
      intramucosal carcinoma. A few residual foci of specialized intestinal metaplasia
      consistent with Barrett's esophagus without dysplasia were identified at the
      proximal and distal ends of the lesion. Immunohistochemically, this lesion
      revealed a pattern of expression of apomucins (MUC5AC diffusely positive, MUC1
      and MUC6 focally positive, and MUC2 negative) consistent with a gastric foveolar
      phenotype. In addition, in the dysplastic areas, there was high Ki-67 labeling
      index and no overexpression of p53 protein. In our opinion, this case represents
      a precursor lesion of an extremely well-differentiated adenocarcinoma of gastric
      foveolar phenotype that has been previously documented in the stomach and in the
      duodenum and that now for the first time we report in the esophagus in
      association with Barrett's intestinal metaplasia.

PMID- 18724241
TI  - Hypothalamic papillary tumor in a patient with tuberous sclerosis.
AB  - We here report an unusual tumor of the suprasellar region featuring a papillary
      growth pattern and cytokeratin expression in a 10-year-old boy with tuberous
      sclerosis. This hitherto undescribed low-grade hypothalamic tumor extends the
      spectrum of tumors associated with the tuberous sclerosis complex.

PMID- 18724242
TI  - Multiple hybrid granular cell tumor-perineuriomas.
AB  - Hybrid peripheral nerve sheath tumors (PNSTs) are recently recognized, rarely
      reported entities. Very few hybrid PNSTs with elements of perineurioma have been
      reported. We report a case of a 47-year-old man who presented with multiple (>20)
      cutaneous nodules on all 4 extremities, present since childhood. The patient and
      his family had no history of other PNSTs, other neural-origin tumors, or genetic
      disorders, including neurofibromatosis. Five excised lesions are well
      circumscribed but unencapsulated nodular tumors composed of cytologically bland
      spindled cells with tapering nuclei and indistinct cytoplasm arranged in a
      storiform pattern in a collagenous matrix. Scattered among these cells are large
      granular eosinophilic cells. The spindled cells are epithelial membrane antigen
      positive and S-100 protein negative. The cytoplasm of the granular cells contains
      abundant S-100 protein, NK1/C3, and CD68-positive granules. Sparse nerve
      fascicles contain neurofilament-positive axons. Each tumor also contains poorly
      marginated areas that histologically resemble pure granular cell tumor, and
      superficial biopsies of these tumors can histologically resemble pure granular
      cell tumors. Considering a Schwannian origin for both perineurial and granular
      cells can provide a logical explanation for the pathogenesis of this case. To the
      best of our knowledge, our case is the first report of multiple hybrid granular
      cell tumor-perineurioma.

PMID- 18724243
TI  - Expression of pax8 as a useful marker in distinguishing ovarian carcinomas from
      mammary carcinomas.
AB  - The ovary is a common site of involvement for metastasis and the breast is one of
      the most common sources. Metastatic breast carcinoma can mimic a primary ovarian
      carcinoma. Pax8 is a crucial transcription factor for organogenesis of the
      thyroid gland, kidney, and Mullerian system, and it also regulates Wilms tumor
      suppressor gene (WT1) expression. A total of 124 cases of ovarian carcinomas (84
      serous papillary, 18 endometrioid, 12 mucinous, 10 clear cell) and 243 cases of
      invasive breast carcinomas (178 ductal, 65 lobular) were immunostained with Pax8
      and WT1 by tissue microarrays to see the differential expression. Pax8 reaction
      was found in 108 of 124 ovarian carcinomas (87.1%) generally in diffuse staining,
      including 81 of 84 serous papillary carcinomas (96.4%), 16 of 18 endometrioid
      carcinomas (88.9%), 10 of 10 clear cell carcinomas (100%), and 1 of 12 mucinous
      carcinomas (8.3%), whereas WT1 expression was seen in 78 of 124 ovarian
      carcinomas (62.9%), including 73 of 84 serous papillary carcinomas (86.9%), and 5
      of 18 endometrioid carcinomas (27.8%), with no expression in all 10 clear cell
      carcinomas and 12 mucinous carcinomas. All the mammary carcinomas were completely
      negative for Pax8, but WT1 expression was seen in 5 of 243 cases (2.1%). Pax8 is
      a useful marker in the differential diagnosis of ovarian and breast carcinomas,
      and it seems to be superior to WT1 for the diagnosis of all types of nonmucinous
      ovarian carcinomas, notably clear cell and endometrioid types where WT1
      expression is generally negative or only focal.

PMID- 18724244
TI  - Familial gastrointestinal stromal tumors caused by the novel KIT exon 17 germline
      mutation N822Y.
AB  - Gastrointestinal stromal tumors (GISTs) are most often associated with oncogenic
      mutations of the KIT gene resulting in activation of the tyrosine kinase receptor
      KIT. Familial GIST syndrome based on a hereditary predisposition to develop GIST
      owing to a germline mutation is exceedingly rare. We describe a kindred with
      familial GIST displaying a novel germline mutation in exon 17. Three siblings (2
      females, 1 male; 42 to 49 y) underwent surgery for multiple intra-abdominal
      tumors within a 3-year period. Their father had been operated on for gastric and
      jejunal tumors 20 years previously. The GIST was confirmed by
      immunohistochemistry in each sibling. Tumor and blood samples of the family
      members were analyzed for mutations in KIT and platelet-derived growth factor
      receptor (PDGFRalpha) genes. All examined lesions were of spindle cell type with
      expression of CD117. The tumor material exhibited a novel point mutation in codon
      822 in exon 17 resulting in the replacement of asparagine by tyrosine (N822Y).
      The same mutation was detected in the father's blood sample. One healthy brother
      of the 3 siblings showed a wild-type sequence of the KIT gene. The germline
      mutation in exon 17 of the KIT gene identified in this kindred is very different
      from previously reported mutations of the KIT gene in familial GIST. Although the
      penetrance of KIT mutations is as yet unknown, assessment of the unaffected
      kindred of GIST patients for the presence of this mutation could help to
      distinguish individuals at high risk from those at virtually no risk.

PMID- 18724245
TI  - Multiple sporadic gastrointestinal stromal tumors (GISTs) of the proximal stomach
      are caused by different somatic KIT mutations suggesting a field effect.
AB  - Multifocal gastrointestinal stromal tumors (GISTs) are observed in patients with
      germline KIT or PDGFRA mutations, and in those with neurofibromatosis 1. However,
      the pathogenesis of apparently sporadic multifocal gastric GISTs in adults is
      poorly understood. We analyzed 27 GISTs from 11 patients (mean age, 75 y) with 2
      to 4 tumors each. All tumors represented incidental findings in surgical (n=8)
      and autopsy (n=3) specimens and were located in the gastric body or fundus within
      < or =4 cm distance from each other. The 8 surgical cases represented 10% of
      GISTs involving the proximal stomach in our case material. Tumor size ranged from
      1.5 mm to 45 mm (mean, 9 mm). Histology revealed a uniform spindle cell
      morphology with a variable sclerosis/calcification and a low mitotic activity (<5
      mitoses/50 high-power fields). All tumors were KIT+/CD34+. Nineteen of 22 tumors
      (79%) revealed mutations in KIT exon 11 (13 deletions and 6 point mutations).
      Individual lesions from the same patient displayed different mutations in all,
      but 1 case, thus ruling out germline mutations and neurofibromatosis 1. Our
      findings indicate that multifocal gastric GISTs in elderly patients are unrelated
      to hereditary GIST syndromes. Clustering of these lesions in the proximal
      stomach, their close proximity, and the demonstration of different KIT mutations
      in individual lesions from the same patient point to the existence of distinct
      subsets of interstitial cells of Cajal with a higher propensity for different
      somatic KIT exon 11 mutations, possibly as a result of a field effect involving
      premutational epigenetic alterations or yet unidentified etiologic factors.

PMID- 18724246
TI  - Ischemic fasciitis: analysis of 44 cases indicating an inconsistent association
      with immobility or debilitation.
AB  - Ischemic fasciitis is a rare pseudosarcomatous proliferation of atypical
      fibroblasts described to be located over bony protuberances and said to develop
      most often in immobile elderly or debilitated patients. We report the
      clinicopathologic features of 44 cases of this pseudosarcomatous reactive
      fibroblastic/myofibroblastic proliferation. There were 15 female and 29 male
      patients between 23 and 96 years of age (median: 74 y). Tumor size, known in 34
      cases, ranged from 1.3 to 10 cm (median: 4.7 cm). The lesions developed mostly in
      the deep subcutis (27 cases) and infiltration of deep dermis, muscle, and
      tendinous tissue was sometimes observed. In 3 cases, the lesion developed within
      skeletal muscle. In 33 cases (76.7%), the tumor was located around the limb
      girdles and sacral region; 5 tumors each (23.3%) occurred on the chest wall and
      the back. A history of physical debilitation could be confirmed in only 7
      patients. Nine patients had a history of chronic or malignant diseases and 4
      patients had a history of local trauma. The histologic hallmark of this reactive
      proliferation is a zonal appearance with central fibrinoid degeneration/necrosis
      and cystic changes surrounded by a granulation tissuelike vascular component,
      mixed with plump amphophilic reactive fibroblasts and myofibroblasts
      morphologically similar to proliferative fasciitis. Immunohistochemistry was
      performed in 18 cases, showing focal positivity for smooth muscle actin (37.5%),
      desmin (40%), or both (14.3%), underlining the fibroblastic/myofibroblastic
      nature of these lesions, whereas S-100 and Pan-keratin were consistently
      negative. Follow-up data were available in 13 cases and ranged between 6 and 72
      months (median: 31.3 mo); local recurrence was observed in 1 case in which the
      patient was physically debilitated. Recognition of this distinct entity as a
      reactive process, by no means always associated with debilitation, is essential
      to avoid confusion with soft tissue sarcomas.

PMID- 18724247
TI  - Acinar cell carcinoma of the pancreas metastatic to the ovary: a report of 4
      cases.
AB  - We report 4 cases of acinar cell carcinoma of the pancreas, 3 presenting as
      metastases in the ovary, the first report of this circumstance, which may pose a
      broad differential diagnosis and caused significant diagnostic difficulty in all
      the cases. The average patient age was 57 (range: 28 to 81) years. In 3 cases,
      the ovarian tumors were detected before the pancreatic tumor; in 1 case, a large
      abdominal mass and ovarian tumors were discovered synchronously. The ovarian
      tumors were large, solid, white-tan on gross examination, and bilateral in 3
      cases; the single case involving only 1 ovary had 2 discrete masses of tumor.
      Microscopic examination showed highly cellular neoplasms with a small amount of
      fibrous stroma. Two cases had a predominant acinar growth pattern of cells with
      brightly eosinophilic, granular cytoplasm. In 2 cases, the pattern was
      predominantly solid-cribriform with areas of comedolike necrosis, and the cells
      had pale eosinophilic, finely granular cytoplasm. Nuclei in all cases were
      uniform with prominent nucleoli. The main differential diagnostic consideration
      was well-differentiated neuroendocrine neoplasm (carcinoid tumor); positive
      immunostaining with antibodies against chymotrypsin and trypsin and negative
      immunostaining with antibodies against synaptophysin and chromogranin helped
      exclude this diagnosis. We observed focal alpha-inhibin immunostaining in 2
      cases, which may represent a potential diagnostic pitfall, as a Sertoli cell
      tumor or unusual granulosa cell tumor may also enter the differential diagnosis.
      Inclusion of antibodies against the pancreatic enzymes chymotrypsin and trypsin
      in the immunohistochemical panel is critical in establishing the correct
      diagnosis and should be considered when evaluating ovarian tumors with
      architectural (mainly acinar) and cytologic (granular eosinophilic cytoplasm)
      characteristics that should bring a metastatic acinar cell carcinoma into
      consideration.

PMID- 18724248
TI  - Grading of invasive cribriform carcinoma on prostate needle biopsy: an
      interobserver study among experts in genitourinary pathology.
AB  - The distinction between cribriform Gleason pattern 3 and 4 prostate cancer is
      controversial. Out of 3590 prostate cancers sent to one of the authors over 7
      months, 30 needle biopsy cases were selected that possibly represented cribriform
      Gleason pattern 3 cancer. Thirty-six digital images were taken and sent to 10
      experts in prostate pathology. Consensus was defined when at least 7/10 experts
      agreed on the grade. Sixty-seven percent (n=24) of images reached consensus (23
      pattern 4; 1 pattern 3). Of the 12 nonconsensus images, 7 were favor pattern 4
      (6/10 experts agreed), 1 was favor pattern 3 (6/10 experts agreed), and 4 were
      equivocal (<6 experts agreed). The most common criteria used to call pattern 4 in
      the 23 consensus pattern 4 images were in frequency: irregular contour, irregular
      distribution of lumens, slit-like lumens, large glands, number of glands, and
      small lumens. In the only consensus pattern 3 image, criteria used were regular
      contour, small glands, regular distribution of lumens, and uniform round lumens.
      Discrepancy between experts was qualified as primarily objective (different
      criteria present) in 38%, subjective (different interpretation of the same
      criteria) in 12%, and mixed (both objective and subjective) in 50%. The most
      frequent situation with different interpretations of the same criteria were
      regular versus irregular contour and small versus large glands, with the former
      more common. Even in this highly selected set of images thought to be the best
      candidates for cribriform pattern 3 from a busy consult service, most experts
      interpreted the cribriform patterns as pattern 4. Moreover, most of the
      cribriform foci investigated (73%) were associated with more definitive pattern 4
      elsewhere on the needle biopsy specimen. In conclusion, most of the small
      cribriform cancer foci seen on needle biopsy should be interpreted as Gleason
      pattern 4 and not pattern 3.

PMID- 18724249
TI  - SIRT1 expression is associated with poor prognosis of diffuse large B-cell
      lymphoma.
AB  - Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase.
      Recently, it is suggested that SIRT1 may be involved in the development of
      malignant tumors including mouse lymphoma. Therefore, we investigated the
      prevalence and the prognostic impact of SIRT1 expression in diffuse large B-cell
      lymphoma (DLBCL). Immunohistochemical expression of SIRT1, p53, bcl2, CD10, bcl6,
      and multiple myeloma-1 (MUM1) were evaluated by using a 2 mm core from 104 DLBCL
      patients for tissue microarray. Positive expression of SIRT1 was seen in 74%
      (77/104) of patients. In total DLBCL patients, SIRT1 and p53 expression were
      significantly associated with shorter overall survival (OS) by univariate
      analysis (P=0.001 and P=0.011, respectively). SIRT1 was also an independent
      prognostic factor by multivariate analysis (P=0.01). According to the expression
      patterns of CD10, bcl6, and MUM1, germinal center B cell (GCB) types were
      represented in 38 cases (37%) and non-GCB types were represented in 66 cases
      (63%). In the GCB type, only p53 expression was associated with a significantly
      shorter OS (P=0.032). In the non-GCB type, expression of SIRT1 correlated with
      shorter OS by univariate analyses (P=0.005) and multivariate analyses (P=0.049).
      In conclusion, we showed that SIRT1 expression is a clinically significant
      prognostic indicator for DLBCL patients.

PMID- 18724250
TI  - Comparison of commercially available serologic kits for the detection of celiac
      disease.
AB  - BACKGROUND: The sensitivity and specificity of current antihuman tissue
      transglutaminase (tTG) IgA assays used to detect celiac disease reportedly
      approach 100%. In addition, the sensitivity of new generation deamidated gliadin
      peptide (alpha-DGP) antibody assays has also been reported to be similar to the
      tTG IgA assays. In routine clinical practice, however, the sensitivities and
      specificities of these tests for diagnosing celiac disease seem to be lower. AIM:
      We analyzed sensitivities and specificities of 4 IgA tTG and 3 deamidated gliadin
      peptide (alpha-DGP) kits. METHODS: The performance of 4 tTG IgA assays, A: Inova
      (Hu red blood cell), B: Binding site (rHu Ag), C: Eurospital (rHu Ag), D: Immco
      (rHu Ag) and 3 Inova alpha-DGP assays, E: alpha-DGP-IgA, F: alpha-DGP-IgG, and G:
      alpha-DGP-IgA+G was evaluated using sera from different subsets of celiac disease
      patients and controls; group 1: active celiac disease n=28, group 2: gluten-free
      diet n=54, group 3: healthy controls n=40, group 4: disease controls n=57(Crohn's
      disease n=17, chronic hepatitis n=40). RESULTS: Using the manufacturer's cut-off
      values, the sensitivities and specificities of different kits ranged from 71.4%
      to 96.4% and 87.5% to 100%, respectively. When group 1 was compared with disease
      controls, sensitivities remained the same but specificities decreased. Receiver
      operating characteristic plot derived cut-off values modified decision thresholds
      in all assays except kit (G). Kappa analysis demonstrated variable degrees of
      agreement. All assays demonstrated higher sensitivities for patients with higher
      grades of villous atrophy. CONCLUSIONS: Overall sensitivity was at or below 90%,
      which is lower than that reported in the literature. Performance of the
      recombinant and red blood cell antigen-based tTG assays was similar, whereas the
      alpha-DGP assays demonstrated lower values. Receiver operating characteristic
      plot derived cut-off values altered test results. Many factors affect the results
      of these tests and clinicians should be aware of their limitations.

PMID- 18724251
TI  - Clinical characteristics of inflammatory bowel disease in Turkey: a multicenter
      epidemiologic survey.
AB  - AIM: To investigate the epidemiologic and clinical characteristics of
      inflammatory bowel disease (IBD) patients in a large multicenter, countrywide,
      hospital-based study in Turkey. MATERIALS AND METHODS: Twelve centers uniformly
      distributed throughout Turkey reported through a questionnaire the new IBD cases
      between 2001 and 2003. The incidence of ulcerative colitis (UC) and Crohn's
      disease (CD) has been reported per 100,000 people. Epidemiologic features and
      clinical characteristics of both diseases were analyzed. RESULTS: During the
      study period, 661 patients of UC and 216 patients of CD were identified. The
      incidence in the referral population was 4.4/100,000 and 2.2/100,000 for UC and
      CD, respectively. The age of the patients showed the characteristic biphasic
      distribution with 2 peaks between 20 and 30 and 50 and 70 years. A male
      predominance was observed in both diseases. A history of smoking was detected in
      15.5% of UC patients and 49.3% of patients with CD. Family history was positive
      in 4.4% in UC and 8.3% in CD patients. Concomitant amebiasis was observed in
      17.3% of patients with UC and 1.3% of patients with CD. A history of appendectomy
      was reported in 15% of patients with CD and only 3% of patients with UC. Both
      extraintestinal and local complications were more frequent in CD patients,
      whereas arthritis was most common in both diseases. CONCLUSIONS: IBDs are
      frequently encountered in Turkey. IBD incidence is lower than North and West
      Europe but close to Middle East in our country. The majority of IBD cases are
      diagnosed in young people (20 to 40 y) with predominance in males. The rate of
      both intestinal and extraintestinal complications in our population was low when
      compared with the data reported in the literature. IBD and especially UC, can
      coexist with amebiasis or become manifest with amebic infestation. The presence
      of concomitant ameba may create confusion and cause dilemmas in the diagnosis and
      treatment of UC.

PMID- 18724252
TI  - Feasibility and findings of colonoscopy for living-donor liver transplant
      candidates.
AB  - BACKGROUND AND AIMS: Living-donor liver transplantation (LDLT) has been widely
      performed in patients with end-stage liver disease and hepatocellular carcinoma
      in Japan. Although extrahepatic cancer survey for LDLT candidates is absolutely
      required, few reports have indicated the optimal surveillance method for
      colorectal cancer. The aim of this study is to investigate the feasibility and
      findings of colonoscopy before LDLT. PATIENTS AND METHODS: From January 2004 to
      August 2006, we prospectively enrolled all of the scheduled LDLT candidates of
      our hospital for pretransplant colonoscopy examination. RESULTS: A total of 81
      patients were enrolled for colonoscopy. Of these patients, 67 (83%) could
      actually undergo colonoscopy. Patients who could not undergo colonoscopy
      exhibited more impaired liver function than those who could (median Model End
      Stage Liver Disease score; 25.5 vs. 14.5, P=0.0003). Among patients who underwent
      colonoscopy, observation of total colon was attained in 64 (96%). Neoplasia was
      found in 28 (42%) patients, including 4 patients with adenomas > or =10 mm, 1
      patient with adenomas with high-grade dysplasia, and 3 patients with invasive
      cancer. Patients who had advanced neoplasia (adenoma > or =10 mm, adenomas with
      high-grade dysplasia, or invasive cancer) were likely to have a lower performance
      status (PS) (7/8 were PS 3) than those who did not (P=0.054). CONCLUSIONS:
      Clinically significant tumors were found in a considerable portion of LDLT
      candidates, particularly in lower PS patients. Because immunosuppressive agents
      after transplantation may worsen malignant tumors, colonoscopy before
      transplantation is recommended in patients who can tolerate the procedure.

PMID- 18724253
TI  - fMRI of intrasubject variability in ADHD: anomalous premotor activity with
      prefrontal compensation.
AB  - OBJECTIVE: Children with attention-deficit/hyperactivity disorder (ADHD)
      consistently display increased intrasubject variability (ISV) in response time
      across varying tasks, signifying inefficiency of response preparation compared to
      typically developing (TD) children. Children with ADHD also demonstrate impaired
      response inhibition; inhibitory deficits correlate with ISV, suggesting that
      similar brain circuits may underlie both processes. To better understand the
      neural mechanisms underlying increased ISV and inhibitory deficits in children
      with ADHD, functional magnetic resonance imaging was used to examine the neural
      correlates of ISV during Go/No-go task performance. METHOD: Event-related
      functional magnetic resonance imaging was used to study 25 children with ADHD and
      25 TD children ages 8 to 13 years performing a simplified Go/No-go task. Brain
      behavior correlations were examined between functional magnetic resonance imaging
      activation and ISV within and between groups. RESULTS: For TD children, increased
      rostral supplementary motor area (pre-supplementary motor area) activation during
      No-go events was associated with less ISV, whereas the reverse was true for
      children with ADHD for whom increased pre-supplementary motor area activation was
      associated with more ISV. In contrast, children with ADHD with less ISV showed
      greater prefrontal activation, whereas TD children with more prefrontal
      activation demonstrated more ISV. CONCLUSIONS: These findings add to evidence
      that dysfunction of premotor systems may contribute to increased variability and
      impaired response inhibition in children with ADHD and that compensatory
      strategies eliciting increased cognitive control may improve function. However,
      recruitment of prefrontal resources as a compensatory mechanism for motor task
      performance may preclude the use of those prefrontal resources for higher order,
      more novel executive functions with which children with ADHD often struggle.

PMID- 18724254
TI  - Remission status and cortical thickness in childhood-onset schizophrenia.
AB  - OBJECTIVE: Few studies have examined prediction of schizophrenia outcome in
      relation to brain magnetic resonance imaging measures. In this study, remission
      status at the time of discharge was examined in relation to admission cortical
      thickness for childhood-onset schizophrenia probands. We hypothesized that total,
      frontal, temporal, and parietal gray matter thickness would be greater in
      patients who subsequently remit. METHOD: The relation between admission cortical
      brain thickness on magnetic resonance imaging and remission status at the time of
      discharge an average of 3 months later was examined for 56 individuals (32 males)
      ages 6 to 19 diagnosed with childhood-onset schizophrenia. Cortical thickness was
      measured across the cerebral hemispheres at admission. Discharge remission
      criteria were adapted from the 2005 Remission in Schizophrenia Working Group
      criteria. RESULTS: Patients remitted at discharge (n = 16 [29%]) had thicker
      regional cortex in left orbitofrontal, left superior, and middle temporal gyri
      and bilateral postcentral and angular gyri (p < or = .008). CONCLUSIONS: Our
      results provide neuroanatomic correlates of clinical remission in schizophrenia
      and evidence that response to treatment may be mediated by these cortical brain
      regions.

PMID- 18724255
TI  - Correlates of accommodation of pediatric obsessive-compulsive disorder: parent,
      child, and family characteristics.
AB  - OBJECTIVE: Pediatric obsessive-compulsive disorder (OCD) is a chronic, impairing
      condition associated with high levels of family accommodation (i.e.,
      participation in symptoms). Understanding of factors that may engender
      accommodation of pediatric OCD is limited. This study conducted exploratory
      analyses of parent-, child-, and family-level correlates of family accommodation,
      considering both behavioral and affective components of the response. METHOD: The
      sample included 65 youths (mean age 12.3 years, 62% male) with OCD and their
      parents who completed a standardized assessment battery composed of both clinical
      and self-report measures (e.g., Children's Yale-Brown Obsessive-Compulsive Scale,
      Brief Symptom Inventory). RESULTS: Family accommodation was common, with the
      provision of reassurance and participation in rituals the most frequent practices
      (occurring on a daily basis among 56% and 46% of parents, respectively). Total
      scores on the Family Accommodation Scale were not associated with child OCD
      symptom severity; however, parental involvement in rituals was associated with
      higher levels of child OCD severity and parental psychopathology and with lower
      levels of family organization. Comorbid externalizing symptomatology and family
      conflict were associated with parent report of worse consequences when not
      accommodating. CONCLUSIONS: Although these findings must be interpreted in light
      of potential type I error, they suggest that accommodation is the norm in
      pediatric OCD. Family-focused interventions must consider the parent, child, and
      family-level variables associated with this familial response when teaching
      disengagement strategies.

PMID- 18724257
TI  - Trajectories of childhood aggression and inattention/hyperactivity: differential
      effects on substance abuse in adolescence.
AB  - OBJECTIVE: Aggression and hyperactivity/inattention each are linked to risk of
      alcohol use disorder (AUD), but their unique contributions remain ambiguous. The
      present study disaggregated these two domains developmentally and examined the
      relation between childhood behavior trajectories and adolescent substance use.
      METHOD: A total of 335 children of alcoholic and nonalcoholic fathers were
      studied prospectively. Parallel process latent trajectory class analysis was
      developed with behavioral ratings by parents and teachers of aggression and
      inattention/hyperactivity across ages 7 to 16. Membership in the four latent
      classes was used as a predictor for problem adolescence alcohol use and substance
      onset. RESULTS: Youths in the four latent trajectory classes differed in number
      of alcohol problems at age 16: healthy class (39% of sample, mean 2.1 alcohol
      related problems), inattentive/hyperactive but not aggressive (33%; mean 2.7
      problems), aggressive but not inattentive/hyperactive (4%, mean 5.0 problems),
      and comorbid (24%; mean 4.0 problems). Survival analysis revealed that the
      aggressive, comorbid, and inattentive/hyperactive classes had significantly
      earlier onsets of drinking, drunkenness, and marijuana use than the healthy
      class. Illicit drug use was also significantly increased in the comorbid,
      aggressive, and inattentive/hyperactive classes compared to the healthy class.
      CONCLUSIONS: Three levels of behavioral risk of substance abuse exist, the
      highest having trajectories of increased aggressive and inattentive/hyperactive
      problems throughout childhood, the next involving only an increased
      inattentive/hyperactive behavioral trajectory, and the lowest involving those
      with neither type of problem. Children with both inattention/hyperactivity and
      aggression have the greatest need for childhood intervention to prevent substance
      abuse in adolescence.

PMID- 18724256
TI  - CBCL pediatric bipolar disorder profile and ADHD: comorbidity and quantitative
      trait loci analysis.
AB  - OBJECTIVE: The pediatric bipolar disorder profile of the Child Behavior Checklist
      (CBCL-PBD), a parent-completed measure that avoids clinician ideological bias,
      has proven useful in differentiating patients with attention
      deficit/hyperactivity disorder (ADHD). We used CBCL-PBD profiles to distinguish
      patterns of comorbidity and to search for quantitative trait loci in a genomewide
      scan in a sample of multiple affected ADHD sibling pairs. METHOD: A total of 540
      ADHD subjects ages 5 to 18 years were assessed with the Schedule for Affective
      Disorders and Schizophrenia for School-Age Children-Present and Lifetime version
      and CBCL. Parents were assessed with the Schedule for Affective Disorders and
      Schizophrenia-Lifetime version supplemented by the Schedule for Affective
      Disorders and Schizophrenia for School-Age Children for disruptive behavioral
      disorders. Patterns of psychiatric comorbidity were contrasted based on the CBCL
      PBD profile. A quantitative trait loci variance component analysis was used to
      identify potential genomic regions that may harbor susceptibility genes for the
      CBCL-PBD quantitative phenotype. RESULTS: Bipolar spectrum disorders represented
      less than 2% of the overall sample. The CBCL-PBD classification was associated
      with increased generalized anxiety disorder (p =.001), oppositional defiant
      disorder (p =.008), conduct disorder (p =.003), and parental substance abuse (p
      =.005). A moderately significant linkage signal (multipoint maximum lod score =
      2.5) was found on chromosome 2q. CONCLUSIONS: The CBCL-PBD profile distinguishes
      a subset of ADHD patients with significant comorbidity. Linkage analysis of the
      CBCL-PBD phenotype suggests certain genomic regions that merit further
      investigation for genes predisposing to severe psychopathology.

PMID- 18724258
TI  - Neuropsychiatric disorders associated with streptococcal infection: a case
      control study among privately insured children.
AB  - OBJECTIVE: To assess whether antecedent streptococcal infection(s) increase the
      risk of subsequent diagnosis of obsessive-compulsive disorder (OCD), Tourette
      syndrome (TS), other tic disorders, attention-deficit/hyperactivity disorder
      (ADHD), or major depressive disorder (MDD) in a national sample of privately
      insured children. METHOD: Using health insurance claims data, we compared the
      prior year's occurrence of streptococcal infection in children ages 4 to 13 years
      with OCD, TS, or tic disorder newly diagnosed between January 1998 and December
      2004 to that of a cohort of matched controls. Conditional logistic regression
      models were used to determine the association of prior streptococcal sore throat
      or scarlet fever with a diagnosis of OCD, TS, or tic disorder. We repeated the
      analyses for two other infectious diseases (otitis media and sinusitis) and one
      noninfectious condition (migraine). We also investigated the potential
      specificity of this association by performing similar analyses focused on newly
      diagnosed ADHD and newly diagnosed MDD. RESULTS: Subjects with newly diagnosed
      OCD, TS, or tic disorder were more likely than controls to have had a diagnosis
      of streptococcal infection in the previous year (odds ratio 1.54, 95% confidence
      interval 1.29-2.15). Prior streptococcal infection was also associated with
      incident diagnoses of ADHD (odds ratio 1.20, 95% confidence interval 1.06-1.35)
      and MDD (odds ratio 1.63, 95% confidence interval 1.12-2.30). CONCLUSIONS: These
      findings provide epidemiologic evidence that some pediatric-onset
      neuropsychiatric disorders, including OCD, tic disorders, ADHD, and MDD, may be
      temporally related to prior streptococcal infections. Whether this is the result
      of a nonspecific stress response or secondary to an activation of the immune
      system remains to be determined.

PMID- 18724260
TI  - The impact of surgery in the management of the head and neck carcinoma involving
      the carotid artery.
AB  - OBJECTIVES/HYPOTHESIS: To demonstrate the feasibility of the carotid artery
      dissection and/or resection and reanastomosis, and to show its positive impact on
      survival and disease control rates for the head and neck carcinomas involving the
      carotid artery. STUDY DESIGN: Tertiary center (Comprehensive Cancer Center). Case
      series review. METHODS: The data of 90 patients with head and neck malignancies
      involving the carotid artery were operated for the carotid artery dissection
      and/or resection, and reanastomosis in the last 10 years were retrospectively
      reviewed and analyzed. RESULTS: Eighty (89%) of the 90 patients' head and neck
      malignancies were squamous cell carcinoma. Fifty-two (65%) and 28 (35%) of 80
      patients were recurrent and stage IV disease, respectively. There was no stage I
      to III disease. Carotid artery was dissected and preserved in 64 (71.1%) of the
      90 patients. Eighteen (20%) of 90 patients needed carotid artery dissection with
      resection and reanastomosis. Eight (8.9%) patients were unresectable. Sixty (75%)
      of 80 patients needed reconstruction with regional or free flaps and grafts.
      Overall 2- and 5-year estimated survivals were 32.4% and 27.8% for all; 14.3% and
      10.7% for recurrent; 64.3% and 57.8% for stage IV previously untreated; and 22.0%
      and 22.0% for carotid artery resected-reanastomosed patients, respectively.
      CONCLUSIONS: The carotid artery dissection without resection is an achievable
      goal in majority of patients with the advanced stage head and neck carcinoma
      involving the carotid artery. Resection and reanastomosis of carotid artery,
      especially in the previously untreated carotid involved patients, is a feasible
      surgery and achieves better survival and disease control rates when compared with
      the unresected or recurrent disease patients.

PMID- 18724261
TI  - Quantitative assessment of laryngeal muscle morphology after recurrent laryngeal
      nerve injury: right vs. left differences.
AB  - OBJECTIVES/HYPOTHESIS: Reports of laryngeal response to denervation are
      inconsistent. Some document atrophy and fibrosis in denervated laryngeal muscles,
      whereas others indicate resistance to atrophy. Spontaneous reinnervation has also
      been documented. The goal of this study was to clarify the effects of nerve
      injury and reinnervation on thyroarytenoid (TA) and posterior cricoarytenoid
      (PCA) muscles. STUDY DESIGN: Laboratory experiment. METHODS: TA and PCA muscles
      of cats were harvested 5 to 6 months after transecting right or left recurrent
      laryngeal nerve (RLN). Images of muscle cross-sections were acquired and studied
      using an image analysis workstation. Cross-sectional areas as well as total cross
      sectional area of randomly selected muscle fibers were recorded. RESULTS: TA
      reinnervation was robust on both sides, but there was less reinnervation of the
      PCA muscle after left-sided RLN lesion than after right-sided injury.
      CONCLUSIONS: Differences in reinnervation after RLN injury could contribute to
      the higher clinical incidence of left- vs. right-sided laryngeal paralysis.

PMID- 18724262
TI  - Is cognitive functioning detrimentally affected after early, induced menopause?
AB  - OBJECTIVE: Investigations into the cognitive effects of surgically and chemically
      induced menopause are frequently combined with naturally occurring menopause and
      hormone therapy. However, there is some evidence that women who undergo surgical
      menopause may experience more cognitive decline post surgery as well as more
      benefit from subsequent hormone therapy use than women who experience naturally
      occurring menopause. Little is known about the effects of chemically induced
      menopause on cognitive function. The aim of this review was to examine whether
      premature menopause affects cognitive functioning. DESIGN: PubMed, MEDLINE, and
      PsychINFO searches of the literature published from 1988 to 2007 pertaining to
      the understanding of the relationships between induced menopause and cognitive
      dysfunction were reviewed. Those combining induced menopause with natural
      menopause, those involving a disease process (eg, dementia), and animal studies
      were excluded. RESULTS AND CONCLUSIONS: Although smaller prospective studies have
      found that surgical menopause is associated with specific deficits in the memory
      (visual and verbal) and verbal fluency domains, larger randomized, controlled
      trials have generally found no effect of surgical menopause on cognitive
      functioning. The effects of chemical menopause are harder to assess as only three
      prospective trials have explicitly investigated the effect of induced menopause
      in the context of breast cancer treatment, and the results remain inconclusive.
      However, as surgical and chemical menopause both comprise the abrupt withdrawal
      of estrogen, there is the potential that this process may exert neurobiological
      effects that are different from those occurring with natural menopause and
      further prospective investigations comprising pre- and postsurgical/chemotherapy
      neuropsychological assessments are warranted.

PMID- 18724263
TI  - Long-term risk of depressive and anxiety symptoms after early bilateral
      oophorectomy.
AB  - OBJECTIVE: We studied the long-term risk of depressive and anxiety symptoms in
      women who underwent bilateral oophorectomy before menopause. DESIGN: We conducted
      a cohort study among all women residing in Olmsted County, MN, who underwent
      bilateral oophorectomy before the onset of menopause for a noncancer indication
      from 1950 through 1987. Each member of the bilateral oophorectomy cohort was
      matched by age with a referent woman from the same population who had not
      undergone an oophorectomy. In total, we studied 666 women with bilateral
      oophorectomy and 673 referent women. Women were followed for a median of 24
      years, and depressive and anxiety symptoms were assessed using a structured
      questionnaire via a direct or proxy telephone interview performed from 2001
      through 2006. RESULTS: Women who underwent bilateral oophorectomy before the
      onset of menopause had an increased risk of depressive symptoms diagnosed by a
      physician (hazard ratio = 1.54, 95% CI: 1.04-2.26, adjusted for age, education,
      and type of interview) and of anxiety symptoms (adjusted hazard ratio = 2.29, 95%
      CI: 1.33-3.95) compared with referent women. The findings remained consistent
      after excluding depressive or anxiety symptoms that first occurred within 10
      years after oophorectomy. The associations were greater with younger age at
      oophorectomy but did not vary across indications for the oophorectomy. In
      addition, treatment with estrogen to age 50 years in women who underwent
      bilateral oophorectomy at younger ages did not modify the risk. CONCLUSIONS:
      Bilateral oophorectomy performed before the onset of menopause is associated with
      an increased long-term risk of depressive and anxiety symptoms.

PMID- 18724265
TI  - Chronic multifocal osteomyelitis due to Clostridium difficile in an adolescent
      with sickle cell anemia.

PMID- 18724264
TI  - Red clover extract: a putative source for simultaneous treatment of menopausal
      disorders and the metabolic syndrome.
AB  - OBJECTIVE: Currently, red clover extract is used to treat menopausal disorders as
      an alternative to classic hormone therapy. Several human and animal studies have
      attributed hypolipidemic, hypoglycemic, or antiatherosclerotic effects to red
      clover extract or isoflavones. This study was designed to determine the
      peroxisome proliferator-activated receptor (PPAR) gamma activation by red clover
      extract. DESIGN: The PPARgamma binding affinities and the transactivation
      activities of red clover extracts, isoflavones, and their metabolites were
      analyzed. The presence of specific substances in the extracts was proved by high
      performance liquid chromatography/electrospray ionization/mass spectrometry.
      RESULTS: The red clover extracts and the compounds genistein and biochanin A were
      potent PPARgamma ligands and activators. Several metabolites exerted higher
      binding affinities or transactivational activities than their precursor
      molecules. 6-Hydroxydaidzein exerted a more than 100-fold higher binding affinity
      than its precursor daidzein. The maximal transactivational activity of 6
      hydroxydaidzein and 3'-hydroxygenistein exceeded even that of rosiglitazone, a
      known PPARgamma agonist. Equol and O-desmethylangolensin showed an approximately
      fivefold higher binding affinity and, in the case of O-desmethylangolensin, a
      fourfold higher PPARgamma agonistic activity than the precursor. The daily dose
      of Menoflavon forte, a widely used red clover extract for treatment of menopausal
      disorders, provides theoretically 15% to 30% of the daily recommended dose of
      rosiglitazone. Considering the more active metabolites formed, activity must be
      higher in vivo. CONCLUSIONS: This study shows that red clover extracts, the major
      compounds, and especially several main metabolites exert significant PPARgamma
      binding and transactivational activity. Red clover extract, which is currently
      used for treating menopausal disorders, could be simultaneously used for
      ameliorating the metabolic syndrome.

PMID- 18724266
TI  - A cluster of childhood empyema cases in Brooklyn.

PMID- 18724267
TI  - Host's response in otitis media: understanding genetic susceptibility.
AB  - Increasing evidence is emerging on genetic factors affecting host's response to
      infection in the middle ear. This review summarizes current knowledge on the
      field and on the contribution of nonspecific barriers, innate, and adaptive
      immunity. Better understanding of susceptibility to this very common disease will
      facilitate identification of high-risk individuals and optimization of prevention
      and treatment.

PMID- 18724268
TI  - Development of amplitude-integrated electroencephalography and interburst
      interval in the rat.
AB  - Continuous monitoring of electrocortical brain activity with amplitude-integrated
      electroencephalography (aEEG) is important in neonatology. aEEG is affected by,
      for example, maturity, encephalopathy, and drugs. Neonatal research uses rat pups
      of different ages. Postnatal day (P) 7 rats are suggested to be equivalent
      neurodevelopmentally to near-term infants. We hypothesized that
      electroencephalography (EEG) and aEEG in P1-P21 rats follow the same
      developmental pattern with respect to background activity and the longest
      interburst interval (IBI) as that seen in infants from 23-wk gestational age (GA)
      to post-term. We examined aEEG and EEG on 49, unsedated rat pups with two
      clinical monitors. aEEG traces were analyzed for lower and upper margin
      amplitude, bandwidth and the five longest IBI in each trace were measured from
      the raw EEG. The median longest IBI decreased linearly with age by 5.24 s/d on
      average. The lower border of the aEEG trace was <5 microV until P7 and rose
      exponentially reaching 10 microV by P12. This correlated strongly with the
      decrease in IBI; both reflect increased continuity of brain activity with
      postnatal age. Based on aEEG trace analysis, the rat aEEG pattern at P1
      corresponds to human aEEG at 23-wk gestation; P7 corresponds to 30-32 wk and P10
      to 40-42 wk.

PMID- 18724269
TI  - Black women in the United States decrease their number of recent sex partners:
      temporal trends from the national survey of family growth.

PMID- 18724270
TI  - Antimicrobial susceptibility of Neisseria gonorrhoeae strains isolated in 2004
      2006 in Bangui, Central African Republic; Yaounde, Cameroon; Antananarivo,
      Madagascar; and Ho Chi Minh Ville and Nha Trang, Vietnam.
AB  - GOAL: To investigate the in vitro antimicrobial susceptibility of Neisseria
      gonorrhoeae strains isolated in 2004 and 2005 in Bangui, Central African
      Republic; Yaounde, Cameroon; Antananarivo, Madagascar; and Ho Chi Minh Ville and
      Nha Trang, Vietnam. STUDY DESIGN: Antimicrobial susceptibility testing was
      performed by both disk diffusion and agar dilution methods according to Clinical
      and Laboratory Standards Institute (CLSI) recommendations. Minimum inhibitory
      concentrations (MICs) to 5 antimicrobials (penicillin G, ceftriaxone,
      ciprofloxacin, spectinomycin, and tetracycline) were determined when feasible.
      Penicillinase-producing N. gonorrhoeae (PPNG) was analyzed by the paper
      acidometric method (nitrocefin test). RESULTS: Thirty N. gonorrhoeae isolates
      from Bangui could be studied, 79 from Yaounde, 126 from Antananarivo, 56 from Nha
      Trang, and 126 from Ho Chi Minh Ville in 2004 and 2005. Unfortunately, because of
      problems of electricity supply, no strains could be recovered for the
      determination of MICs in Yaounde, and only 68 strains could be tested in
      Antananarivo and 121 in Ho Chi Minh Ville. Patterns of resistance were similar in
      Antananarivo, Bangui, and Yaounde but different from those observed in Vietnam.
      Ciprofloxacin was highly effective in Africa, but nearly all strains in Vietnam
      were resistant to this drug. Overall, ceftriaxon and spectinomycin were the best
      antibiotics, with one strain resistant to spectinomycin in Antananrivo and one
      strain resistant to ceftriaxon in Ho Chi Minh Ville. CONCLUSIONS: Ciprofloxacin
      remains highly efficient in Madagascar and Central Africa, ceftriaxone and
      spectinomycin should be used as the first-line antimicrobial agents in treating
      gonorrhea in Vietnam.

PMID- 18724271
TI  - Basic principles of polarity establishment and maintenance. Conference on
      Mechanisms of Cell Polarity.

PMID- 18724272
TI  - HAND transcription factors are required for neonatal sympathetic neuron survival.
AB  - Expression of the basic helix-loop-helix transcription factor HAND2 begins early
      in sympathetic neuron development and is essential for the differentiation of
      noradrenergic neurons. Here, we show that the expression of HAND2 and related
      HAND1 are maintained in sympathetic neurons throughout fetal and postnatal
      development when these neurons depend on target-derived nerve growth factor (NGF)
      for survival. Short interfering RNA knockdown of endogenous HAND2 and, to a
      lesser extent, HAND1 in neonatal sympathetic neurons cultured with NGF, reduced
      the expression of the NGF receptor tyrosine kinase TrkA (tropomyosin-related
      kinase A), as well as neuronal survival. Chromatin immunoprecipitation analysis
      showed that NGF promotes HAND2 binding to the TrkA minimal enhancer and that
      transfection of sympathetic neurons with a TrkA expression plasmid rescued the
      neurons from HAND knockdown. These findings show that HAND transcription factors
      have a crucial function in sustaining the survival of neonatal sympathetic
      neurons with NGF by a feed-forward loop that maintains the expression of TrkA.

PMID- 18724273
TI  - PR-SET7 and SUV4-20H regulate H4 lysine-20 methylation at imprinting control
      regions in the mouse.
AB  - Imprinted genes are important in development and their allelic expression is
      mediated by imprinting control regions (ICRs). On their DNA-methylated allele,
      ICRs are marked by trimethylation at H3 Lys 9 (H3K9me3) and H4 Lys 20 (H4K20me3),
      similar to pericentric heterochromatin. Here, we investigate which histone
      methyltransferases control this methylation of histone at ICRs. We found that
      inactivation of SUV4-20H leads to the loss of H4K20me3 and increased levels of
      its substrate, H4K20me1. H4K20me1 is controlled by PR-SET7 and is detected on
      both parental alleles. The disruption of SUV4-20H or PR-SET7 does not affect
      methylation of DNA at ICRs but influences precipitation of H3K9me3, which is
      suggestive of a trans-histone change. Unlike at pericentric heterochromatin,
      however, H3K9me3 at ICRs does not depend on SUV39H. Our data show not only new
      similarities but also differences between ICRs and heterochromatin, both of which
      show constitutive maintenance of methylation of DNA in somatic cells.

PMID- 18724274
TI  - Synthetic biology: discovering new worlds and new words.

PMID- 18724275
TI  - Two non-infectious forms of endophthalmitis after intravitreal triamcinolone and
      cataract extraction.

PMID- 18724276
TI  - Photoreceptor integrity and visual acuity in cystoid macular oedema associated
      with retinitis pigmentosa.
AB  - AIMS: To assess the correlation between macular morphology and visual acuity in
      retinitis pigmentosa (RP) patients with cystoid macular oedema (CME). DESIGN:
      Retrospective cross-sectional study. PATIENTS AND METHODS: Forty-one eyes of 25
      RP patients with CME. Patients underwent cross-sectional scans with optical
      coherence tomography (Stratus OCT). Age, total retinal thickness, photoreceptor
      thickness, and the transverse and vertical lengths of the cystoid space were
      measured. Correlation between visual acuity and each of the measurements were
      examined. Additionally, the status of the inner segment/outer segment junction
      (IS/OS) was classified as being absent, discontinuous, or distinct. Measurements
      were then compared among the three groups. RESULTS: Total retinal thickness or
      photoreceptor thickness was not correlated with visual acuity. There was a
      correlation between the transverse length of the cystoid space and visual acuity,
      although the correlation coefficient was weak (r=0.30). The logMAR visual acuity
      in the IS/OS absent group (0.67+/-0.43) was worse than that seen in the IS/OS
      discontinuous (0.22+/-0.19) or IS/OS distinct groups (0.07+/-0.16) (P<0.001).
      CONCLUSIONS: When monitoring CME associated with RP, the status of IS/OS is the
      essential parameter that needs to be examined.

PMID- 18724277
TI  - The role of registries in facilitating clinical research in BMT: examples from
      the Center for International Blood and Marrow Transplant Research.
AB  - Observational databases, such as those maintained by the Center for International
      Blood and Marrow Transplant Research (CIBMTR) and the European Blood and Marrow
      Transplant Group (EBMT), play an important role in facilitating research into
      hematopoietic SCT (HCT) outcomes. The CIBMTR maintains a large database of the
      outcome of BMTs performed in 450 centers in 47 countries, including information
      on 240,000 transplant recipients and adding information on about 14,000 new
      transplants per year. The database has data for 9000 survivors followed for 10 or
      more years. The database may facilitate the understanding of outcomes by
      addressing questions difficult to answer through clinical trials. Clinical
      databases may also aid the development of optimal designs for prospective
      clinical trials. Use of the CIBMTR database for trial design and monitoring is an
      integral part of the US Blood and Marrow Transplant Clinical Trials Network (BMT
      CTN). The establishment of international outcomes registries was an important
      component of advances in HCT over the past three decades. Future progress will be
      further enhanced by inter-registry collaboration through the Worldwide Blood and
      Marrow Transplant Group (WBMT).

PMID- 18724278
TI  - Bone marrow and stem cell transplantation: Malaysian experience.
AB  - Malaysia conducted the first BMT in the country in 1987. Since then, there have
      been 1155 transplantations performed in a total of eight transplant centres. A
      majority of the transplantations were allogeneic, including myeloablative and
      nonmyeloablative. A vast majority of donors are HLA identical siblings. The mean
      age of transplanted patients was 26 years. The major reason for transplantation
      was hematological malignancies. The overall survival was 60% for allogeneic
      transplantation and 52% for autologous transplantation. The most common cause of
      death in transplanted patients was the underlying disease followed by infection
      related complications. Currently, the government is expanding the existing public
      cord blood bank as well as the local donor registry.

PMID- 18724279
TI  - Present and future of hematology and stem cell transplantation in Morocco.
AB  - The first hematology department in Morocco was created in Casablanca in 1980 and
      it is still the only public facility where adult patients can be treated for
      hematological diseases. Two other units treat pediatric hematological disorders
      and cancer. Some patients are treated in private clinics located primarily in
      Casablanca and Rabat. The public hospitals have very limited resources and rely
      heavily on nongovernmental organizations (NGOs) for the care of these patients.
      The NGOs have also played an important role in developing successful cooperative
      programs with hospitals and groups in Europe and the United States. Till 2004,
      all patients who needed BMT and could afford the cost went to Europe. In 2004,
      SCT was initiated in Casablanca, with a four-bed ward set up and properly
      equipped. By May 2007, 27 patients have received autologous PBSCs. With 15
      patients in continuous CR, the program is considered a success so far. The
      development of allogeneic transplantation in Morocco planned in the current year
      is also considered a real challenge.

PMID- 18724281
TI  - Allogeneic stem cell transplantation for chronic myeloid leukemia-status in 2007.
AB  - Whereas until 2000 allo-SCT was the recommended treatment for all new patients
      with CML who were eligible on grounds of age and donor availability, approaches
      to initial therapy have changed very substantially since the introduction of
      imatinib mesylate. Today topical questions are (1) Should any newly diagnosed
      patient receive SCT as primary therapy? (2) How should imatinib failure be
      defined? (3) Should a patient who has failed imatinib but is still in chronic
      phase be offered an SCT or further treatment with a 'second-generation' TKI? (4)
      Would prior treatment with imatinib or concomitant delay to transplant adversely
      affect the subsequent results of allo-SCT? (5) Once the decision to proceed with
      allo-SCT is taken, how exactly should this be performed? (6) If a patient
      relapses after allo-SCT, how should he/she be treated? These questions will be
      addressed, but definitive answers may not yet be possible.

PMID- 18724280
TI  - Hematopoietic stem cell transplantation in Oman.
AB  - Hematopoietic SCT (HSCT) is an integral part of the management of patients with
      hematologic disorders. The Sultanate of Oman, with a population of 2.3 million,
      has an HSCT program based in the Sultan Qaboos University (SQU) hospital.
      Initiated in 1995, this two-bed unit continues to be the only program in the
      country. Between June 1995 and August 2006, a total of 128 patients underwent
      HSCT in this center, averaging about 10-12 transplants per year. The median age
      of these patients was 11 years (2 months to 45 years). Hematologic malignancies
      (49%) and inherited disorders (42%) constituted the major transplant indications,
      whereas BM failure accounted for the remaining. The majority of transplants
      carried out so far have been HLA-matched sibling-donor allogeneic HSCTs. Among
      the inherited disorders, homozygous beta-thalassemia and primary immunodeficiency
      are important transplant indications in this center. The approximate cost of an
      uncomplicated transplant in this center is US$50,000. The success of this program
      has now led to the initiation of a new and larger HSCT complex to provide the
      opportunity for more patients to benefit from this treatment modality within the
      country.

PMID- 18724282
TI  - The stem cell transplant program in Pakistan--the first decade.
AB  - Stem cell transplantation is curative in a number of otherwise fatal
      hematological diseases. In Pakistan, SCT was started in October 1995 at Dr
      Ziauddin Hospital by Dr Tahir Shamsi and his team. The first case was of a young
      man suffering from AML. In 1999, allogeneic BMT was started at Bismillah Taqee
      Institute of Health Sciences and Blood Diseases Centre, Karachi. In 2001, the
      Armed Forces Bone Marrow Transplant Centre, started functioning. Since then, over
      350 allogeneic stem cell transplants have been carried out in these latter two
      centers. Another 50 autologous procedures were carried out in all centers. In
      2004, a third center started transplants at the Aga Khan Hospital. The main
      indications for transplant are aplastic anemia, beta-thalassemia major and
      hematological malignancies. HLA-identical sibling donors provide stem cells for
      the recipient. In 70% of cases, a matched donor is identified. In sharp contrast
      to the rest of the world, the majority of transplants are allogeneic, donor
      recipient pairs are CMV positive and fungal infection, tuberculosis and malaria
      are particular problems. The early results are promising, with transplant-related
      mortality reported to be 10-20%, whereas long-term survival is reported to be 78,
      72 and 49% in aplastic anemia, beta-thalassemia major and leukemia, respectively.
      Financial constraints, poor socioeconomic status, poor transfusion services,
      trained human resources and difficulty in keeping pace with technological
      advances are major hurdles in the growth of transplant medicine. Government
      support is badly needed to strengthen existing facilities and to develop more
      centers.

PMID- 18724283
TI  - The status of blood and marrow transplantation in Philippines.
AB  - The first blood and marrow transplant in Philippines was successfully performed
      in 1990, but despite this early start and the opening of two other transplant
      centers, only 21 transplants have been performed in two of the three existing
      transplant centers. The low number of transplants is due to several factors
      including the prohibitive cost.

PMID- 18724284
TI  - Stem cell transplantation programme at Singapore General Hospital.
AB  - The adult transplant programme at Singapore General Hospital (SGH) was
      established in 1985 and more than 820 transplants have been performed to date. An
      average of about 60 adult transplants (autologous and allogeneic) are performed
      each year. Transplants offered at SGH run the range from autologous to mismatched
      cord and unrelated transplants. Special interests of the transplant programme
      include non-myeloablative transplants in aplastic anaemia, cell therapy protocols
      including cytokine-induced killer cells, patterns of GVHD, cord blood
      transplantation for autoimmune diseases and graft engineering. A cGMP (good
      manufacturing practice) cell therapy laboratory was recently established to
      facilitate bench-to-bedside translational cell therapy trials. A BMT consortium
      has been formed among the various paediatric and adult transplant centres for
      harmonization of protocols and research activities.

PMID- 18724285
TI  - Immunohematopoietic stem cell transplantation: introduction and 35 years of
      development in South Africa--the historical and scientific perspective.
AB  - Bone marrow was the traditional graft source when we introduced these procedures
      to South Africa. Technical details were established using rabbits as the
      experimental model with translation into a formally structured clinical programme
      at the University of Cape Town, based in the Groote Schuur Hospital, in 1972.
      Lack of any infrastructure was overcome by the acquisition of the first
      continuous-flow cell separator in sub-Sahara to provide for granulocyte
      transfusions. This was shortly followed by creating a dedicated platelet donor
      panel and establishing a specialized laboratory for clonogenic assays, flow
      cytometry, and programmed freezing and by including cryopreservation. Development
      was constant and seamless but four distinct periods are recognizable. First,
      guided and constantly encouraged by Professor E Donnall Thomas, was the use of an
      unfractionated mononuclear population derived from multiple sternal and iliac
      crest aspirations where complications, as in other centres, included rejection
      and, particularly troublesome, acute as well as chronic GVHD. The second was
      centred on CsA in association with Professor Jean Borel at Sandoz in Basle,
      leading to a decrease in the incidence and severity of the latter immunologic
      phenomena but not to their abrogation. Third was the opportunity of working with
      Professor Herman Waldmann and Dr Geoff Hale, first in Cambridge and latterly in
      Oxford, on immunosuppression achieved by ex vivo T-cell depletion within the
      broad ambit of the Campath users group. It was here that there was pioneered the
      alternative new approach of adding the anti-CD 52 MoAb only to the graft in what
      has become known as the in-the-bag technique. The fourth, securely based on early
      laboratory and clinical experiences, was a switch to the use of PBSCs mobilized
      into the circulation with stimulatory peptides. In 1995, this original transplant
      team relocated to a new academic centre in the private sector and has continued
      to actively refine the programme over the subsequent decade: the facility at
      Groote Schuur hospital continues independently. Early recognition that
      accountability for these expensive and high profile procedures was an important
      obligation led to consecutive transplants being reported to the International and
      Autologous registries and now continuing to the Centre for Bone Marrow Transplant
      Research concurrently with the European Bone Marrow Transplant Registry. This
      disciplined approach has ensured that all data undergo constant audit and, on
      such a basis, underpin the unbroken accreditation extending over more than three
      and a half decades. With difficulties in finding sibling donors, a further
      achievement was the creation of The South African Bone Marrow Registry and now a
      proposal to also start a national transplant registry that will complement the
      survey currently being conducted, on a worldwide basis, by the European Group for
      Blood and Marrow Transplantation. It is concluded that a properly constituted and
      functioning multidisciplinary team can cost-effectively carry out
      immunohematopoietic stem cell grafting even in an under-resourced country with an
      outcome approximating that reported from recognized First World reference
      centres. The caveat is that, outside such comprehensive units, results may be
      less impressive, thereby arguing for resource allocation being directed to
      academically designated, rather than incentive-driven, preferred providers.

PMID- 18724286
TI  - Current status of hematopoietic stem cell transplantation in Taiwan.
AB  - In Taiwan, hematopoietic SCT (HSCT) has been used to treat patients with
      hematological diseases since 1983. Since then, more than 2200 patients have
      undergone HSCT in 15 large hospitals. The disease entities included acute
      leukemia in 37% of cases, non-Hodgkin's lymphoma in 26%, CML in 10%, multiple
      myeloma in 7% and severe aplastic anemia in 6%. The conditioning regimens used
      were mainly myeloablative (84% of cases). Non-myeloablative regimens were
      fludarabine-based. The average age of allogeneic recipients was at least 10 years
      older than those in the era before their application. The grafts of all patients
      were derived from peripheral blood in 85% of cases, BM in 13% and cord blood (CB)
      in 2%. Forty percent of HSCT patients received autologous grafts, whereas more
      than 25% of allogeneic HSCT patients received grafts from unrelated donors, and
      overall, there were more than 200 Taiwan HSCT recipients. Currently, CB has been
      used successfully in pediatric patients with thalassemia major and also in adult
      patients with hematological malignancy. After transplantation, there was a
      relatively lower prevalence of acute GVHD. However, a relatively higher
      proportion of hepatitis B carriers in the recipients had led to a higher
      incidence of viral reactivation and clinical hepatitis, which was dramatically
      decreased following lamivudine prophylaxis. In conclusion, HSCT has been
      successfully adapted to routine clinical care in Taiwan. Several important
      findings contributing to the progress of HSCT in the past two decades have also
      been noticed on this island.

PMID- 18724287
TI  - Hematopoietic stem cell transplantation in Thailand.
AB  - Hematopoietic SCT was first performed in Thailand in 1986. At present, there are
      FOUR active centers: Siriraj, Ramathibodi, Chulalongkorn and Pramongkutklao
      Hospitals. The annual number of transplants varies from 120 to 150 cases.
      Although the number of eligible patients is high, only a proportion of the
      patients can undergo hematopoietic SCT due to the high cost of the procedure. The
      overall results are comparable to those reported in the Western countries. The
      incidence of acute GVHD is low, whereas chronic GVHD is high, especially in those
      who receive PBSC.

PMID- 18724288
TI  - Allogeneic hematopoietic stem cell transplantation in Tunisia.
AB  - In 1998, the Tunisian team of the 'Centre National de Greffe de Moelle Osseuse'
      initiated allogeneic hematopoietic SCT (AHSCT) in Tunisia. As of June 2007,
      information was collected about 299 patients with a first AHSCT and 12 additional
      retransplants. The median age was 19 years (range 2-49 years). The main
      indications were aplastic anemia (n=106, 36%), leukemia and nonmalignant
      disorders (n=153, 51%), Fanconi anemia (n=26, 9%) and other nonmalignant
      disorders (n=14, 4%). Preparative regimens depended on indication. All donors
      were HLA geno-identical. The stem cell sources were BM (87%) and PBSCs (13%). At
      the time of analysis, 200 patients (67%) were alive after a median follow-up of
      42 months (range 3-112 months). The overall TRM rate was 17%. Outcome depended on
      indication. According to our results, allogeneic HSCT is potentially curative for
      hematological diseases, but it is a toxic approach for malignant disorders.

PMID- 18724289
TI  - Current status of blood and marrow transplantation for patients with AML.
AB  - During the past decade it has become apparent that patients can be transplanted
      successfully after preparation with regimens of reduced intensity. Reduced
      intensity preparations have resulted in lower morbidity and mortality during the
      pre-engraftment period, but have not reduced later occurring infections, GVHD and
      relapse. Outcome-determining risk factors that characterize patients at diagnosis
      as well as during their course include age, cytogenetic configuration,
      hematopoietic elements and a previous history of myelodysplasia or cytoreductive
      therapy for a pre-existing malignancy. These factors are complemented by the
      response to induction therapy and subsequent treatments as well as by the
      duration of the response. More recently, gene expression profiling of leukemic
      cells has added a new dimension to simultaneously assessed biological risk
      factors that may ultimately lead to individuation of therapy.

PMID- 18724290
TI  - Turkish Transplant Registry: a comparative analysis of national activity with the
      EBMT European Activity Survey.
AB  - SCT is a curative approach using chemo-, radio- and immunotherapy for malignant
      and non-malignant hematological disorders. The European Group for Blood and
      Marrow Transplantation (EBMT) has been collecting yearly data on a survey basis
      since 1990. The variables within the survey are limited to detailed indications,
      number of patients, transplant type, stem cell source, type of conditioning
      regimen and donor type. The transplant rates in certain indications, patterns of
      stem cell source selection and donor availability and alternative donor use were
      analyzed in detail. The Turkish transplant registry data within EBMT-European
      Activity Survey (EBMT-EAS) were delivered by the EBMT Activity Survey Office. We
      compared the national data with the international EBMT-EAS data pool.

PMID- 18724291
TI  - Current status of hematopoietic stem cell transplantations in Vietnam.
AB  - In Vietnam, the first three cases of Allo-BMT were successfully performed in 1995
      at the Blood Transfusion and Hematology Hospital (BT-H) of Ho Chi Minh City.
      Donors were HLA fully matched siblings (HLA-A, HLA-B and HLA-DRB1). The patients
      were a 26-year-old man with CML in chronic phase (CP), a 12-year-old woman with
      beta-thalassemia/Hb E and a 9-year-old girl with beta-thalassemia/Hb E. All
      patients were engrafted with the median time to recover ANC>0.5 x 10(9)/l, and
      platelet count >20 x 10(9)/l was 16 and 38 days. At 12 years after
      transplantation, all three patients are alive and well. Today, Vietnam has five
      SCT centers; in the north, there are three centers: 108 Military Hospital,
      Pediatric Institute and Blood transfusion and Hematology Institute; in the middle
      of Vietnam is Hue Hospital and in the south, the BT-H Hospital of Ho Chi Minh
      City. Until now, 65 patients have had SCT in Vietnam; among them, 52 patients had
      SCT at the BT-H Hospital, Ho Chi Minh City. Because of no connection of data
      between different SCT centers, we present here only the results performed at the
      BT-H Hospital, Ho Chi Minh City. With Allo-SCT we performed 19 cases with 3
      procedures: BMT (4 cases), PBSC (6 cases) and cord blood transplantation (9
      cases); patients were diagnosed with AML (n=7), ALL (n=1), CML (n=5) and beta
      thalassemia (n=6). Following transplantation, 7 patients (36.84%) relapsed, 12
      (63.16%) remained alive and overall survival times: 6.81+/-1.35 years, disease
      free survival times: 6.69+/-1.4 years (range 0.5-12 years). With Auto-SCT: since
      November 1996, we have performed 33 cases of autologous PBSC transplantation
      consisting of without cryopreservation (24 cases) and with cryopreservation (9
      cases); patients were diagnosed with AML in CR1 (n=21), ALL in CR1 (n=6), CML in
      CP (n=5) and non-Hodgkin's lymphoma in CR1 (n=1). The median age of the patients
      was 35 years (range 18-46). The median time to recover ANC >0.5 x 10(9)/l and
      platelet count >20 x 10(9)/l was 14 days (range 9-25 days) and 35 days (range 9
      120 days). Following transplantation, 18 patients (54.50%) relapsed, 15 (45.45%)
      remained alive and overall survival times: 5.74+/-0.82 years and disease-free
      survival times: 5.48+/-0.92 years. There was no statistically significant
      difference of overall survival and disease-free survival between Allo-SCT and
      Auto-SCT procedures (P>0.05). These preliminary data suggest that HSCTs have been
      used as one of the standard treatments for hematological diseases and
      malignancies in Vietnam and that cord blood is an alternative source of
      hematopoietic stem cells for allogeneic transplantation in children.

PMID- 18724292
TI  - Allogeneic hematopoietic cell transplantation for adults with ALL.
AB  - ALL is a heterogeneous disease, and outcomes vary by patient age, immunophenotype
      and clinical, cytogenetic and molecular features. Modern treatment strategies use
      a risk-adapted approach. The optimal post-remission therapy for adults with ALL
      remains unclear. Available data indicate no consensus as to whether there is an
      advantage to allogeneic hematopoietic cell transplant (Allo-HCT) over
      chemotherapy for the consolidation of adults with ALL with standard risk features
      while in the first CR (CR1). However, Allo-HCT is recommended in CR1 for patients
      with high-risk ALL, for those in a second CR (CR2) and for certain other subsets
      of patients with this disease.

PMID- 18724293
TI  - Transplantation for children with acute lymphoblastic leukemia.
AB  - EFS for children with ALL continues to increase and is predicted to reach 90%
      with current therapy. Better understanding of leukemia cell biology and
      pharmacogenetics has led to the design of more effective treatment and also
      refined the prognostic features associated with a poor outcome. ALL characterized
      by the translocation t(9;22) or t(4;11), or by a hypodiploid karyotype or by an
      incomplete response to induction therapy is likely to relapse. SCT for ALL is
      largely used to treat patients failing primary chemotherapy but is selectively
      included as part of initial therapy for children at high risk for relapse. If SCT
      is going to become the primary therapy for children with ALL in first remission,
      the regimen-related mortality must approach 0%, and the risk for severe acute and
      chronic GVHD should be less than 5%. Salvage therapy after ALL relapse remains
      the major indication for SCT. The time required to find a suitable match has led
      to the use of cord blood and haploidentical related donors as stem cell sources.
      For children who relapse, SCT is likely to remain the principal option to promote
      survival. Efforts to reduce both the risk of relapse and the transplant regimen
      toxicity, both immediate and delayed, must continue.

PMID- 18724294
TI  - Current status of autologous hematopoietic stem cell transplantation in myeloma.
AB  - High-dose melphalan with autologous hematopoietic SCT (HSCT) improves response
      rates and survival in myeloma. This is despite the fact that unlike other
      hematologic malignancies treated with high-dose therapy and autotransplantation,
      autografted myeloma patients continue to relapse several years after
      transplantation and the procedure is not curative in the majority of patients.
      However, patients surviving for several years with essentially normal quality of
      life may be considered to be 'operationally cured.' Also, unlike with other
      hematologic malignancies relapsing after an autograft, recurrent disease can be
      treated with novel agents or repeat high-dose chemotherapy and autologous or
      allogeneic HSCT--and long-term survival is seen in a number of patients after
      relapse. Although tandem transplantation is clearly superior to a single
      autograft, it is unclear if this should be offered to all patients routinely or
      only to those not attaining CR after one transplant. It is also unclear if novel
      agents should be used before transplantation or reserved for relapse. Despite
      their excellent activity, there is no evidence that novel agents such as
      thalidomide, bortezomib and lenalidomide can replace high-dose chemotherapy and
      HSCT, and the best strategy is to use all options in all eligible patients at
      appropriate stages of the disease.

PMID- 18724295
TI  - The US National Marrow Donor Program role in unrelated donor hematopoietic cell
      transplantation.
AB  - The National Marrow Donor Program (NMDP) is headquartered in Minneapolis,
      Minnesota, USA. Established in 1986, the NMDP currently operates the world's
      largest registry of unrelated adult donors and umbilical cord blood (UCB) units.
      Since its inception, the NMDP has benefited from continuous financial support
      provided by the US government through a series of contracts and grant awards.
      This funding has supported a large network of donor centers and the recruitment
      of millions of potential adult hematopoietic cell (HC) donors. More recently, the
      federal government has also supported a national registry for UCB units and
      expansion of the available UCB inventories. Today, the NMDP registry lists more
      than 6.7 million adult donors and 68,000 UCB units. Seventy-seven percent (5.2
      million) of the adult donors and virtually all of the UCB units are fully typed
      for HLA A, B and DR. An additional 5 million donors are available for search
      through international collaborations. The NMDP currently facilitates more than
      3600 recipients each year totaling more than 29,000 transplants since 1987.

PMID- 18724296
TI  - Allogeneic transplantation following nonmyeloablative conditioning for aggressive
      lymphoma.
AB  - Allogeneic hematopoietic SCT following myeloablative conditioning is associated
      with a high nonrelapse mortality and usually reserved for young, medically fit
      patients. The use of allogeneic stem cells is associated with a less risk of
      relapse, but is also associated with the risk of GVHD. The increased antitumor
      activity is due to graft-vs-tumor immune responses. The newer use of
      nonmyeloablative or reduced-intensity conditioning has decreased the toxicity of
      this approach and allows the treatment of older patients or those with medical
      comorbidities that preclude the use of a myeloablative regimen. A
      nonmyeloablative regimen using fludarabine and 2 Gy TBI was developed in Seattle
      that reliably allows allogeneic engraftment from either matched related or
      unrelated donor stem cell sources. Here we describe our results using this
      regimen in multicenter studies for the treatment of aggressive non-Hodgkin's
      lymphoma (NHL) and mantle cell NHL.

PMID- 18724297
TI  - High-dose chemotherapy and autologous stem cell transplantation for Hodgkin's
      lymphoma in the kingdom of Saudi Arabia: King Faisal specialist hospital and
      research center experience.
AB  - We report our experience with high-dose chemotherapy (HDC) and autologous SCT
      (ASCT) in 66 patients out of 113 (113 patients out of 153 had complete analysis)
      with primary refractory Hodgkin's lymphoma (PR-HL) who received salvage
      chemotherapy followed by BEAM as HDC. Median age at ASCT was 23 years. Before
      salvage chemotherapy, stages I:II:III:IV were 2:21:14:29, bulky disease 27%,
      involvement of mediastinum 79%, spleen 26% and extranodal site 47%; 92% had ESHAP
      (etoposide, methylprednisolone, high-dose cytarabine, cisplatin) as salvage. Post
      ASCT evaluation showed response in 50 patients (76%), complete response (CR) in
      37 (56%), partial response in 14 (21%), no response or stable disease in three
      (5%) and progressive disease in 10 (15%) patients. Six patients achieved CR after
      XRT (5) or surgery (1), making a total with CR of 43 (65%). From diagnosis and
      HDC, median follow-up is 38.5 and 22.8 months and median overall survival 78 and
      57 months, respectively. EFS and overall survival (OS) are 36 and 64%,
      respectively. In all 47% patients are in CR. Twenty-two (33%) patients died of
      the disease. Multivariate analysis showed elevated lactic dehydrogenase (LDH) for
      EFS (P=0.041) and mediastinal involvement for OS (P=0.038) as negative prognostic
      factors. In conclusion, EFS and OS are only 36 and 64%, respectively. Elevated
      LDH and mediastinal involvement are poor prognostic factors.

PMID- 18724298
TI  - Hematopoietic stem cell transplantation in thalassemia.
AB  - SCT still remains the only cure currently available for patients with
      thalassemia. Results of transplants in this disease have steadily improved over
      the last two decades due to improvements in preventive strategies, effective
      control of transplant-related complications and development of new preparative
      regimens. Currently, high-resolution HLA typing has enabled physicians to perform
      transplants from unrelated volunteer donors for thalassemia with results
      comparable with those obtained employing an HLA-identical sibling. The
      probabilities for obtaining thalassemia-free survival after transplant in
      thalassemia from an HLA-identical donor, family member or MUD are between 85 and
      87%. Therefore, when an HLA-identical donor is present, the transplant of
      allogeneic stem cell should be performed as allogeneic gene therapy. In the light
      of advances in transplantation for thalassemia, patients with an HLA-identical
      donor should be offered SCT.

PMID- 18724299
TI  - Treatment strategies for patients with severe aplastic anemia.
AB  - Treatment strategies for patients with severe aplastic anemia (SAA), depend on
      the severity of the disease, the age of the patient and the availability of a
      family donor. Progress in the past has included the early use of combined
      immunosuppressive therapy (IST) and better matching strategies to select
      unrelated donors. Currently, the actuarial 10-year survival in 2479 patients
      registered within the European Group for Blood and Marrow Transplantation (EBMT),
      is 73 and 68% for patients receiving first-line BMT or IST. The outcome of BMT
      has significantly improved since 1996, and this is true for both matched sibling
      donor BMT as well as for alternative donor BMT. Survival is significantly better
      in children (<16 years) as compared with adults (79 vs 68%, P<0.0001). In
      contrast, there has been no significant improvement over time for patients
      receiving IST. Again, results were significantly better in children compared with
      adults (81 versus 70%, P=0.001), especially in very severe aplasia (83 versus
      62%, P=0.0002). This report outlines some of these results as a basis for
      treatment strategies in SAA.

PMID- 18724300
TI  - Matched-related allogeneic stem cell transplantation in Saudi patients with
      Fanconi anemia: 10 year's experience.
AB  - Allogeneic SCT is curative for bone marrow failure in Fanconi anemia (FA)
      patients but the optimal conditioning regimen is undetermined. We report here our
      experience with 56 FA patients who underwent allogeneic matched related SCT. The
      conditioning regimen varied according to time of SCT and disease status at SCT;
      22 patients (group A) received Cy 20 mg/kg, thoraco-abdominal radiation and
      antithymocyte globulins (ATG); and 34 patients (group B) received Cy 60 mg/kg and
      ATG. Median time to engraftment was similar (14 days) in both groups. Hemorrhagic
      cystitis was significantly more common in group B. Overall survival and event
      free survival of all patients were 85 and 78.3% respectively. For groups A and B
      respectively, overall survival was 72.5 and 96.9% (P=0.013); and event-free
      survival was 72.5 and 82.3% (P=0.3). The use of the nonradiation Cy/ATG regimen
      in matched related SCT for FA patients offers better overall and event-free
      survival.

PMID- 18724301
TI  - Hematopoietic cell transplantation for correction of primary immunodeficiencies.
AB  - The first hematopoietic cell transplants in humans with durable success were
      reported in 1968, in three patients with primary immunodeficiencies who received
      grafts from HLA-matched siblings (two with SCID and one with Wiskott-Aldrich
      syndrome). Significant progress has been made in correcting lethal primary
      immunodeficiencies (PIDs) with hematopoietic transplantation in the ensuing 40
      years due to several factors: (1) ability to phenotype and quantitate (CD34+)
      hematopoietic stem cells, (2) advent of high-resolution tissue typing, (3)
      availability of closely matched unrelated donor bone marrow, peripheral blood
      stem cells, and cord blood, and (4) the application of reduced intensity
      conditioning regimens pre-transplant. Furthermore, the genetic basis of the
      majority of lethal PIDs has been defined, allowing more accurate studies of the
      natural history of the disorders without HCT intervention, and providing a
      compelling rationale for early transplantation in disorders with median survivals
      of 15-20 years. In the current era, we can identify several factors, which
      influence the ultimate success of HCT for PID. These include the age at
      transplant and general health of the patient. Young age is associated with fewer
      comorbidities and less frequent pre-transplant exposure to herpes family and
      enteric viruses, thus lowering the risks of related post-transplant
      complications. The careful selection of pre-transplant conditioning can
      significantly reduce early TRM in patients with certain immunodeficiencies, and
      increase the probability of durable engraftment in others. Because of the
      specific needs of children with PIDs, HCT from unrelated donors should, ideally,
      be performed in centers with extensive expertise and experience in the treatment
      of such disorders. In such centers, donor selection based on high-resolution
      tissue typing, younger age and specific viral immunity has led to survival rates
      following matched unrelated donor HCT for PIDs, which are very similar to those
      obtained with HCT from matched sibling donors. While ultimate success rates are
      similar, transplant-related management of children receiving unrelated grafts is
      considerably more complicated and prolonged than following matched sibling HCT.

PMID- 18724302
TI  - Stem cell transplantation for primary immunodeficiencies: King Faisal Specialist
      Hospital experience from 1993 to 2006.
AB  - Primary immunodeficiencies constitute a group of highly complex congenital
      disorders most of which are characterized by poor prognosis with high mortality
      and morbidity. Hematopoietic SCT became an established therapy for such
      disorders. The first clear-cut report of successful allogenic SCT in 1968 dealt
      with the treatment of a patient with primary immunodeficiency, that is, SCID and
      Wiskott-Aldrich syndrome. Starting with this pioneering experience in 1968,
      hundreds of SCID patients and hundreds of patients affected by other life
      threatening forms of primary immunodeficiency throughout the world have benefited
      from SCT. Presently, hematopoietic SCT from an HLA-matched sibling donor confers
      at least 80% chance of cure for children affected by primary immunodeficiency and
      about a 70% chance of cure when a fully HLA-matched related donor is available.
      This high success rate is the consequence of better management of nutrition and
      the infection problem affecting these patients at the time of disease.
      Conversely, when a related HLA-mismatched donor is used, the survival rate is
      significantly lower than that of patients receiving SCT from either an HLA
      matched sibling or a fully matched HLA-unrelated donor. Optimal results and
      outcome of SCT are highly dependent on early and correct diagnosis of these
      disorders. SCT should be applied early in the course of the disease to prevent
      irreversible complications from the primary disease and/or infection. We present
      the data on outcome for primary immunodeficiency transplantation at King Faisal
      Specialist Hospital from 1993 to 2006.

PMID- 18724303
TI  - Stem cells: the challenge and opportunities.
AB  - Recent studies have clearly identified that hematopoietic stem cells (HSC) are
      part of a hierarchical organization defined by cells able to initiate long-term
      repopulation (LT-HSC) of injured BM followed by populations with transient
      repopulation ability. As HSCs are able to supply blood cells for the lifespan of
      the individual, LT-HSCs undergo an aging process. The consequences of aging are
      an increase in the stem cell pool size, increased self-renewal and production of
      cells with expression of myeloid-specific genes and genes commonly expressed in
      myeloid leukemia. The age-related increased incidence of myeloproliferative
      disorders is therefore not surprising. Marrow cells circulate and migrate to a
      number of different organs. Previously assumed tissue and organ specificities
      appear to be less stringent and primitive cells residing in one organ may
      contribute to the structural and functional regeneration of other organs. It is
      intriguing to speculate that cells and cytokines used in appropriate
      concentrations may be able to repair damaged organs by using the defective organ
      as a scaffold, thus reducing the need for the transplantation of solid organs.

PMID- 18724304
TI  - The Japan Marrow Donor Program, the Japan Cord Blood Bank Network and the Asia
      Blood and Marrow Transplant Registry.
AB  - The annual number of hematopoietic stem cell transplants in Japan is about 3500,
      which are performed by more than 300 medical teams throughout the country. The
      Japan Marrow Donor Program (JMDP), initiated in 1991, has recruited 300,000
      volunteer donors, accepted 20,000 patients and has facilitated more than 8000
      unrelated bone marrow transplants. The Japan Cord Blood Bank Network (JCBN),
      which started in 1999, has collected 20,000 cord blood units and facilitated 4000
      cord blood transplants up to now. To fulfill the requirement for HSCT,
      international collaborations as well as domestic efforts are considered to be
      important for the future. The Center for International Blood and Marrow
      Transplant Research (CIBMTR) and European Blood and Marrow Transplant Group
      (EBMT) initiated a movement to create a common clinical record form last winter
      and called on the Asia-Pacific Blood and Marrow Transplantation Group (APBMT) to
      join them. Globalization of patient and donor registration for HSCT has become
      realistic and this could contribute to both the further improvement of patient
      outcomes and to further donor safety.

PMID- 18724305
TI  - Haploidentical hematopoietic cell transplantation.
AB  - Haploidentical hematopoietic stem cell transplantation (HSCT) provides an
      opportunity for nearly all patients to benefit from HCT when a HLA genotypically
      matched sibling is not available. Initial results with the use of mismatched
      allografts led to limited enthusiasm due to GVHD and infectious complications
      resulting in unacceptable treatment-related morbidity and mortality. Recent
      advances with effective T-cell depletion, the use of 'megadoses' of stem cells,
      better antimicrobial therapy and reduced intensity conditioning has significantly
      decreased the early transplant-related mortality and GVHD. These modifications
      also enabled robust and prompt engraftment and led to enhancing the therapeutic
      benefits of haploidentical transplantation. However, the cardinal problems
      related to delayed immune reconstitution causing post-transplant infectious
      complications and relapse remain, limiting the efficacy of haploidentical
      transplant. Preliminary data have demonstrated the great potential in the use of
      adoptive cellular immunity and selective allodepletion in rapidly reconstituting
      immunity without GVHD. The encouraging reports from haploidentical transplant
      using noninherited maternal antigen (NIMA)-mismatched donors or natural killer
      (NK) alloreactive donors may greatly increase the donor availability and open a
      way to more appropriate donor selection in HLA-haploidentical HSCT. Future
      challenges remain in determining the safest approach for haploidentical
      transplant with minimal risk of GVHD, while preserving effective GVL activity and
      promoting prompt immune reconstitution.

PMID- 18724306
TI  - Unrelated cord blood transplantation in pediatric patients: the experience of the
      King Faisal Specialist Hospital & Research Center.
AB  - For patients lacking a suitable matched related donor, unrelated cord blood
      transplantation (UCBT) has emerged as a valid alternative with many advantages
      such as easy procurement and acceptable toxicity even with partial HLA
      mismatches. We report here our experience at King Faisal Specialist Hospital
      Research Center (KFSHRC) of 63 patients who underwent partially matched UCBT.

PMID- 18724307
TI  - Immune modulation and chronic graft-versus-host disease.
AB  - As more and more patients undergoing allogeneic hematopoietic SCT (HSCT) survive
      the early post-transplant period, the number of individuals at risk for chronic
      GVHD has grown. Treatment for established cGVHD remains unsatisfactory. No
      experimental agent has demonstrated superiority to steroids alone in a randomized
      clinical trial. Distinguishing chronic from acute graft-versus-host disease is a
      major issue. The importance of achieving clarity in cGVHD diagnosis is critical
      as efforts are undertaken to understand its pathogenesis and to design definitive
      trials that can target prevention and/or treatment. Immune tolerance to self
      antigens may be broken in cGVHD, giving rise to the autoimmune manifestations of
      the disorder. Recent attention has focused on CD4+CD25 regulatory T cells and
      their relationship to cGVHD. Significant enthusiasm has emerged for manipulating
      Treg either ex vivo or in vivo for clinical benefit. Another immunomodulatory
      approach to cGVHD might be the targeting of B lymphocytes and the antibodies they
      produce. As efforts continue to devise strategies to treat and prevent chronic
      GVHD, it is important to acknowledge the link between cGVHD and freedom from
      relapse, at least for certain malignancies.

PMID- 18724309
TI  - CMV infections after hematopoietic stem cell transplantation.
AB  - CMV can cause disease in several different organs after SCT. Seropositivity
      remains a major risk factor for TRM in unrelated SCT patients. In a study using
      the EBMT registry, CMV-seropositive patients receiving seropositive unrelated
      donor grafts had improved survival and reduced TRM compared with those receiving
      seronegative grafts, and a similar result was found in a single center study.
      Preventive measures can be divided into prevention of a primary infection or
      recurrence of CMV (prophylaxis) or prevention of development of disease when a
      reactivation has occurred (preemptive therapy). The standard therapy for CMV
      pneumonia has been i.v. ganciclovir combined with high-dose Ig, but this standard
      has never been evaluated in a controlled study and more recent studies have
      questioned whether the addition of Ig improves outcome.

PMID- 18724308
TI  - Why are there regional differences in stem cell transplantation activity? An EBMT
      analysis.
AB  - Differences in the number of hematopoietic SCTs (HSCT), in transplant rates, in
      indications and in techniques between countries have been reported. They were
      attributed mainly to differences in the economic situation of the countries or to
      differences in prevalences of the disease. On the basis of the results of the
      annual activity survey on HSCT of the European Blood and Marrow Transplantation
      (EBMT), we have analyzed the factors associated with differences between more
      than 600 teams participating from more than 40 countries over a time span of 15
      years. The results show a more complex situation. The gross national income per
      capita, number of transplant teams per 10 million inhabitants or per 10,000 km2,
      team size and team experience all impact on transplant activity. Furthermore,
      hitherto unknown factors must add to the decisions to perform or not to perform
      HSCT. These data illustrate that more research is needed to understand the
      mechanism of HSCT activity and to enable health-care agencies to provide the
      necessary infrastructure.

PMID- 18724310
TI  - Blood and marrow transplantation in the People's Republic of China.
AB  - Syngeneic BMT was first performed successfully in China in 1964. In 1981,
      allogeneic BMT was applied in an acute leukemia patient with success. Since then,
      the number of BMTs has been increasing gradually, especially since the 1990s.
      More than 2000 stem cell transplants per year have been performed in recent years
      in more than 50 BMT units in mainland China. A survey of 16 BMT units from 1986
      to 2005 indicates that the predominant types of transplantation performed are
      identical sibling (36%), related mismatched/haploidentical (11.2%), unrelated
      (7.5%) and autologous (44.5%) and that the distribution of disease entities and
      prevalent diseases being transplanted are AML (31%), ALL (16.1%), CML (19.1%) and
      lymphoid malignancy (22.2%). The number of transplants from unrelated donor or
      related mismatched/haploidentical donor has increased significantly in the past 5
      years. BM and G-CSF-mobilized peripheral blood are used about equally often as a
      source of hematopoietic stem cells, or they are used in combination. Umbilical
      cord blood is used least often. Leukemias for allogeneic and lymphoid
      malignancies for autologous BMT continue to increase, but the increase in BMT for
      CML has been slow since 2004. By the end of 2007, HLA data were available on more
      than 700,000 individuals in the Chinese Marrow Donor Program, and 800 stem cell
      donations have been carried out from these. Related HLA-mismatched/haploidentical
      BMT has achieved comparable outcomes in terms of severe acute GVHD, chronic GVHD,
      relapse, treatment-related mortality, disease-free survival (DFS) and overall
      survival (OS) with HLA-identical sibling transplantation in the author's two BMT
      units. Cord blood co-infusion as the third-party cells could significantly reduce
      the incidence and severity of acute GVHD, steroid-refractory acute GVHD and
      extensive chronic GVHD without an increase in leukemia relapse and could improve
      DFS and OS.

PMID- 18724311
TI  - Hematopoietic stem cell transplantation in Egypt.
AB  - Hematopoietic SCT is now an established treatment modality with definitive
      indications for many hematological disorders. However, this line of treatment
      requires tremendous resources, and it becomes increasingly difficult for
      transplanters practicing in the developing world to reconcile the difference
      between what is possible and what is available. On the basis of 18 years of
      experience and more than 1300 transplants, this article will focus on special
      issues, which we think are important for hematopoietic SCT practices in
      developing countries, taking the program in Egypt as an example that may be
      applicable to other countries in the developing world. The SCT program in Egypt
      started in 1989 on a narrow scale. In 1997, the transplant rate increased
      dramatically with the opening of the SCT unit at the Nasser Institute. Our team
      is registered in the Center for International Blood and Marrow Transplant
      Research. The total number of transplants performed till June 2007 is 1362; 80%
      of the cases are allogeneic and 20% autologous. There are seven other centers in
      Egypt performing mainly autologous transplants.

PMID- 18724312
TI  - Stem cell transplantation in India.
AB  - This paper outlines the BMT activity in India and describes in some detail the
      transplant program at the Christian Medical College, Vellore. In September 2005,
      data from six transplant centers in India were collected and a total of 1540
      transplants have been performed in a country of over one billion population. At
      the center in Vellore, from October 1986 to December 2006, a total of 626
      transplants have been performed in 595 patients, with 28 patients having more
      than one transplant. Thalassemia accounted for a third of these transplants: the
      country has over 20 million carriers and 10,000 children are born each year with
      thalassemia major. The average cost of allogeneic BMT in India is around $15,000
      20,000, and this is considerably lower than the cost in the West. India needs to
      develop more transplant centers with adequately trained personnel, as there is
      great need for them. Improvements in the economy mean that more patients can
      afford this treatment.

PMID- 18724313
TI  - The hematopoietic stem cell transplantation in Indonesia: an unsolved dilemma.
AB  - Allogeneic BMT was performed in Indonesia, but had to be stopped prematurely
      because of the small number of patients. In the beginning, only patients with
      sufficient financial resources to travel to western countries could undergo
      transplant procedures. When neighbouring countries (Singapore and Malaysia) began
      performing transplant, patients were referred to those centres. In both
      countries, the procedure is more economical and therefore patients come from a
      broader range of economic classes. The Indonesian hematologist must deal with the
      post-transplantation side effects, such as GVHD, which are mostly of the chronic
      type of GVHD. The types of the post-transplant complications do not differ too
      much from other centres and need the same treatment used in the transplant
      centres. Hematologists in Indonesia also treat complications of HSCT performed in
      other countries. When there is no recovery of HSCT development in Indonesia so
      far, many commercially oriented companies or centres from other countries see
      Indonesia as a good commercial market and offer services, some of which are not
      scientifically sound. One of the main problems is umbilical cord blood stem cell
      banking from foreign countries, which is eagerly offered to parents expecting a
      baby. Moreover, parents are not fully protected by law. In conclusion, Indonesia
      needs to revive its own HSCT program to serve and protect its own patients of
      being used as commercial targets by other countries.

PMID- 18724314
TI  - Bone marrow and stem cell transplantation at King Hussein cancer center.
AB  - Bone marrow and stem cell transplantation in Jordan has been performed since the
      1990s, but the first comprehensive program was established at King Hussein Cancer
      Center (KHCC) in March 2003. The program, in addition to other health care
      institutions in Amman, serves approximately 5.6 million Jordanians. Also, we
      treat several patients per year from neighboring Arab countries. The program at
      KHCC performs an average of 80 transplants per year. During the past 4 years 320
      patients received transplants at KHCC; 26% of them received an autologous graft
      and 74% allogeneic grafts. Of the allogeneic grafts 91% were taken from matched
      family members, 6.7% were haploidentical from one of the parents, and 2.3% were
      from an unrelated donor or umbilical cord blood. The actuarial overall survival
      among all patients has been around 65%. The most common indication for
      transplantation at KHCC was leukemia/MDS followed by benign nonmalignant
      hematological/immune deficiency/metabolic disorders, with thalassemia major being
      the most common among this group. The cost of SCT is variable and depends on many
      factors including the type of transplant and the attending post-transplant
      complications. The average charge for autologous transplant (both adults and
      pediatrics) is 24,695 JD (one JD equals 1.42 USD), and the average charge for
      allogeneic transplant (both adults and pediatrics) excluding haploidentical
      transplant is 46,787 JD. We have not noticed any peculiar patterns of
      complications following BMT; however, we have seen a high incidence of chronic
      GVHD following minitransplant with fludarabine and single-dose TBI (Seattle
      protocol). At the inception of the program, invasive fungal infection mainly
      related to building construction, and central line complications were
      significant. Measures implemented to control such complications were successful
      to a large extent. We report our results to the EBMT group and we are accredited
      as an unrelated transplantation center. Although from a young program, our group
      has presented abstracts to international conferences.

PMID- 18724315
TI  - The activity of hematopoietic stem cell transplantation in Korea.
AB  - Since the first successful allogeneic hematopoietic SCT (HSCT) was performed in
      Korea in 1983, there has been a noticeable progress in both the quantity and
      quality of HSCT over 24 years. There are 38 HSCT centers in Korea and the number
      of both allogeneic and autologous HSCTs has been increasing every year. As of
      December 2006, a total of 9561 HSCTs have been carried out in Korea, including
      5617 allogeneic (59%) and 3944 autologous HSCTs (41%). The main indications were
      acute leukemia (3979, 78% allogeneic); lymphoma (1244, 90% autologous); myeloma
      (939, 92% autologous) and aplastic anemia (938). Characteristically, severe
      aplastic anemia accounts for a considerable proportion of transplants (10%),
      compared with western countries. Recently, there has been a marked increase in
      the number of unrelated transplants and the usage of PBSCs. The pattern of
      infectious diseases associated with HSCT is quite different. The rapid expansion
      of unrelated donor pools worldwide has changed the outlook of an unrelated donor
      search in Korea.

PMID- 18724316
TI  - Hematopoietic stem cell transplantation in Lebanon: first comprehensive report.
AB  - Hematopoietic SCT (HSCT) has become a curative therapeutic strategy for several
      malignant and nonmalignant diseases. We report the comprehensive results of the
      first 10 years of experience in HSCT from the two major BMT units in Lebanon:
      Makassed University Hospital and the American University of Beirut Medical
      Center. The median and the 5-year overall survival (OS) were 97 months and 58%,
      respectively, for the 84 patients who received allogeneic HSCT, and 60 months and
      50%, respectively, for the 228 patients who received autologous BMT. The results
      for myeloablative allogeneic transplantation were as follows: AML (n=28, 5-year
      OS 58%, 5-year disease-free survival (DFS) 48%), CML (n=9, 5-year OS 66%, 5-year
      DFS 52%), ALL (n=13, 2-year OS 10%, 2-year DFS 10%), thalassemia (n=10, 5-year
      transfusion-free survival 67%). The results for autologous HSCT were as follows:
      diffuse large B-cell lymphoma (DLBCL) in relapse (n=37, 5-year OS 68%, 5-year
      progression-free survival (PFS) 65%), Hodgkin's lymphoma (n=55, 5-year OS 55%, 5
      year PFS 36%), and first-line multiple myeloma (n=71, 5-year OS 53%, 5-year PFS
      24%). For allogeneic transplanted patients, the cumulative TRM was 23% and the
      incidence of acute GVHD was 23%. For autografted patients, TRM was 2.6%. These
      results indicate that despite the relatively low socioeconomic status of the
      Lebanese population, both allogeneic and autologous HSCT are feasible with
      outcomes similar to developed countries.

PMID- 18724317
TI  - A body of evidence.

PMID- 18724318
TI  - Finite resources.

PMID- 18724319
TI  - Green dentistry.

PMID- 18724320
TI  - The hall technique.

PMID- 18724322
TI  - Retirement concern.

PMID- 18724321
TI  - Dry socket secrets.

PMID- 18724324
TI  - Four year study will examine effectiveness of recall intervals.

PMID- 18724325
TI  - Investment of 75M pounds sterling for dentistry in Scotland.

PMID- 18724326
TI  - Damning inquiry report calls for training in learning disabilities to be made
      mandatory.

PMID- 18724328
TI  - More than a quarter of the population not seeing a dentist, national survey
      reveals.

PMID- 18724332
TI  - Pre-operative fasting for intravenous conscious sedation used in dental
      treatment: are conclusions based on relative risk management or evidence?
AB  - Intravenous sedation is a widely used pharmacological method of patient
      management commonly used in dental surgery for the treatment of anxious patients.
      Variety exists in fasting regimes between different centres offering dental
      sedation, with some advocating starvation in line with general anaesthesia
      protocols and others not enforcing starvation at all. The currently available
      guidelines on fasting protocols are ambiguous and open to interpretation partly
      because they are based on expert opinion rather than evidence-based research.
      This article reviews the available evidence on the subject of pre-operative
      fasting and discusses current guidelines.

PMID- 18724333
TI  - Access to special care dentistry, part 5. Safety.
AB  - This article considers the delivery of efficient and effective dental services
      for patients whose disability and/or medical condition may not be obvious and
      which consequently can present a hidden challenge in the dental setting. Knowing
      that the patient has a particular condition, what its features are and how it
      impacts on dental treatment and oral health, and modifying treatment accordingly
      can minimise the risk of complications. The taking of a careful medical history
      that asks the right questions in a manner that encourages disclosure is key to
      highlighting hidden hazards and this article offers guidance for treating those
      patients who have epilepsy, latex sensitivity, acquired or inherited bleeding
      disorders and patients taking oral or intravenous bisphosphonates.

PMID- 18724340
TI  - Nine years of DentEd--a global perspective on dental education.
AB  - This paper describes the three successive and successful DentEd projects, funded
      by the European Union, that established a productive thematic network which
      identified common content within the dental curriculum. It then developed an
      agreed professional profile, with a defined set of competences and a modular
      curriculum for all new dental graduates based on the European Credit Transfer
      System and trends in learning and assessment. The three phases took nine years to
      complete. Phase one investigated all aspects of dental undergraduate education
      and included over 30 visits to different dental schools by teams of dental
      educators. Phase two built on this work and included further visits to dental
      schools. Phase three refined the competency framework that had been developed in
      phase two and culminated in a global dental conference which finalised position
      papers on all aspects of dental education. The work and recommendations of the
      ICT in dental education group are considered in detail in the paper. The projects
      provided the stimulus for a number of European and international collaborations,
      including the web-based International Federation of Dental Education and
      Associations (IFDEA) Knowledge Centre and the International Virtual Dental School
      (IVIDENT), both of which aim to make increasingly sophisticated ICT-based
      educational material available worldwide and to promote international
      understanding.

PMID- 18724357
TI  - STING is an endoplasmic reticulum adaptor that facilitates innate immune
      signalling.
AB  - The cellular innate immune system is essential for recognizing pathogen infection
      and for establishing effective host defence. But critical molecular determinants
      responsible for facilitating an appropriate immune response-following infection
      with DNA and RNA viruses, for example-remain to be identified. Here we report the
      identification, following expression cloning, of a molecule (STING; stimulator of
      interferon genes) that appears essential for effective innate immune signalling
      processes. It comprises five putative transmembrane regions, predominantly
      resides in the endoplasmic reticulum and is able to activate both NF-kappaB and
      IRF3 transcription pathways to induce expression of type I interferon (IFN-alpha
      and IFN-beta ) and exert a potent anti-viral state following expression. In
      contrast, loss of STING rendered murine embryonic fibroblasts extremely
      susceptible to negative-stranded virus infection, including vesicular stomatitis
      virus. Further, STING ablation abrogated the ability of intracellular B-form DNA,
      as well as members of the herpesvirus family, to induce IFN-beta, but did not
      significantly affect the Toll-like receptor (TLR) pathway. Yeast two-hybrid and
      co-immunoprecipitation studies indicated that STING interacts with RIG-I and with
      SSR2 (also known as TRAPbeta), which is a member of the translocon-associated
      protein (TRAP) complex required for protein translocation across the endoplasmic
      reticulum membrane following translation. Ablation by RNA interference of both
      TRAPbeta and translocon adaptor SEC61beta was subsequently found to inhibit
      STING's ability to stimulate expression of IFN-beta. Thus, as well as identifying
      a regulator of innate immune signalling, our results imply a potential role for
      the translocon in innate signalling pathways activated by select viruses as well
      as intracellular DNA.

PMID- 18724358
TI  - Regulatory networks define phenotypic classes of human stem cell lines.
AB  - Stem cells are defined as self-renewing cell populations that can differentiate
      into multiple distinct cell types. However, hundreds of different human cell
      lines from embryonic, fetal and adult sources have been called stem cells, even
      though they range from pluripotent cells-typified by embryonic stem cells, which
      are capable of virtually unlimited proliferation and differentiation-to adult
      stem cell lines, which can generate a far more limited repertoire of
      differentiated cell types. The rapid increase in reports of new sources of stem
      cells and their anticipated value to regenerative medicine has highlighted the
      need for a general, reproducible method for classification of these cells. We
      report here the creation and analysis of a database of global gene expression
      profiles (which we call the 'stem cell matrix') that enables the classification
      of cultured human stem cells in the context of a wide variety of pluripotent,
      multipotent and differentiated cell types. Using an unsupervised clustering
      method to categorize a collection of approximately 150 cell samples, we
      discovered that pluripotent stem cell lines group together, whereas other cell
      types, including brain-derived neural stem cell lines, are very diverse. Using
      further bioinformatic analysis we uncovered a protein-protein network (PluriNet)
      that is shared by the pluripotent cells (embryonic stem cells, embryonal
      carcinomas and induced pluripotent cells). Analysis of published data showed that
      the PluriNet seems to be a common characteristic of pluripotent cells, including
      mouse embryonic stem and induced pluripotent cells and human oocytes. Our results
      offer a new strategy for classifying stem cells and support the idea that
      pluripotency and self-renewal are under tight control by specific molecular
      networks.

PMID- 18724359
TI  - Identification of ALK as a major familial neuroblastoma predisposition gene.
AB  - Neuroblastoma is a childhood cancer that can be inherited, but the genetic
      aetiology is largely unknown. Here we show that germline mutations in the
      anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and
      that activating mutations can also be somatically acquired. We first identified a
      significant linkage signal at chromosome bands 2p23-24 using a whole-genome scan
      in neuroblastoma pedigrees. Resequencing of regional candidate genes identified
      three separate germline missense mutations in the tyrosine kinase domain of ALK
      that segregated with the disease in eight separate families. Resequencing in 194
      high-risk neuroblastoma samples showed somatically acquired mutations in the
      tyrosine kinase domain in 12.4% of samples. Nine of the ten mutations map to
      critical regions of the kinase domain and were predicted, with high probability,
      to be oncogenic drivers. Mutations resulted in constitutive phosphorylation, and
      targeted knockdown of ALK messenger RNA resulted in profound inhibition of growth
      in all cell lines harbouring mutant or amplified ALK, as well as in two out of
      six wild-type cell lines for ALK. Our results demonstrate that heritable
      mutations of ALK are the main cause of familial neuroblastoma, and that germline
      or acquired activation of this cell-surface kinase is a tractable therapeutic
      target for this lethal paediatric malignancy.

PMID- 18724360
TI  - TMEM16A confers receptor-activated calcium-dependent chloride conductance.
AB  - Calcium (Ca(2+))-activated chloride channels are fundamental mediators in
      numerous physiological processes including transepithelial secretion, cardiac and
      neuronal excitation, sensory transduction, smooth muscle contraction and
      fertilization. Despite their physiological importance, their molecular identity
      has remained largely unknown. Here we show that transmembrane protein 16A
      (TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca(2+)-activated
      chloride channel that is activated by intracellular Ca(2+) and Ca(2+)-mobilizing
      stimuli. With eight putative transmembrane domains and no apparent similarity to
      previously characterized channels, ANO1 defines a new family of ionic channels.
      The biophysical properties as well as the pharmacological profile of ANO1 are in
      full agreement with native Ca(2+)-activated chloride currents. ANO1 is expressed
      in various secretory epithelia, the retina and sensory neurons. Furthermore,
      knockdown of mouse Ano1 markedly reduced native Ca(2+)-activated chloride
      currents as well as saliva production in mice. We conclude that ANO1 is a
      candidate Ca(2+)-activated chloride channel that mediates receptor-activated
      chloride currents in diverse physiological processes.

PMID- 18724362
TI  - Photoswitchable fluorescent proteins enable monochromatic multilabel imaging and
      dual color fluorescence nanoscopy.
AB  - Fluorescent proteins that can be reversibly photoswitched between a fluorescent
      and a nonfluorescent state are important for innovative microscopy schemes, such
      as protein tracking, fluorescence resonance energy transfer imaging, sub
      diffraction resolution microscopy and others. However, all available monomeric
      reversibly switchable fluorescent proteins (RSFPs) have similar properties and
      switching characteristics, thereby limiting their use. Here, we introduce two
      bright green fluorescent RSFPs, bsDronpa and Padron, generated by extensive
      mutagenesis of the RSFP Dronpa, with unique absorption and switching
      characteristics. Whereas bsDronpa features a broad absorption spectrum extending
      into the UV, Padron displays a switching behavior that is reversed to that of all
      green fluorescent RSFPs known to date. These two RSFPs enable live-cell
      fluorescence microscopy with multiple labels using a single detection color,
      because they can be distinguished by photoswitching. Furthermore, we demonstrate
      dual-color fluorescence microscopy with sub-diffraction resolution using bsDronpa
      and Dronpa whose emission maxima are separated by <20 nm.

PMID- 18724361
TI  - Vancomycin-resistant enterococci exploit antibiotic-induced innate immune
      deficits.
AB  - Infection with antibiotic-resistant bacteria, such as vancomycin-resistant
      Enterococcus (VRE), is a dangerous and costly complication of broad-spectrum
      antibiotic therapy. How antibiotic-mediated elimination of commensal bacteria
      promotes infection by antibiotic-resistant bacteria is a fertile area for
      speculation with few defined mechanisms. Here we demonstrate that antibiotic
      treatment of mice notably downregulates intestinal expression of RegIIIgamma
      (also known as Reg3g), a secreted C-type lectin that kills Gram-positive
      bacteria, including VRE. Downregulation of RegIIIgamma markedly decreases in vivo
      killing of VRE in the intestine of antibiotic-treated mice. Stimulation of
      intestinal Toll-like receptor 4 by oral administration of lipopolysaccharide re
      induces RegIIIgamma, thereby boosting innate immune resistance of antibiotic
      treated mice against VRE. Compromised mucosal innate immune defence, as induced
      by broad-spectrum antibiotic therapy, can be corrected by selectively stimulating
      mucosal epithelial Toll-like receptors, providing a potential therapeutic
      approach to reduce colonization and infection by antibiotic-resistant microbes.

PMID- 18724363
TI  - Identification of a copper-binding metallothionein in pathogenic mycobacteria.
AB  - A screen of a genomic library from Mycobacterium tuberculosis (Mtb) identified a
      small, unannotated open reading frame (MT0196) that encodes a 4.9-kDa, cysteine
      rich protein. Despite extensive nucleotide divergence, the amino acid sequence is
      highly conserved among mycobacteria that are pathogenic in vertebrate hosts. We
      synthesized the protein and found that it preferentially binds up to six Cu(I)
      ions in a solvent-shielded core. Copper, cadmium and compounds that generate
      nitric oxide or superoxide induced the gene's expression in Mtb up to 1,000-fold
      above normal expression. The native protein bound copper within Mtb and partially
      protected Mtb from copper toxicity. We propose that the product of the MT0196
      gene be named mycobacterial metallothionein (MymT). To our knowledge, MymT is the
      first metallothionein of a Gram-positive bacterium with a demonstrated function.

PMID- 18724364
TI  - A domino effect in antifolate drug action in Escherichia coli.
AB  - Mass spectrometry technologies for measurement of cellular metabolism are opening
      new avenues to explore drug activity. Trimethoprim is an antibiotic that inhibits
      bacterial dihydrofolate reductase (DHFR). Kinetic flux profiling with (15)N
      labeled ammonia in Escherichia coli reveals that trimethoprim leads to blockade
      not only of DHFR but also of another critical enzyme of folate metabolism:
      folylpoly-gamma-glutamate synthetase (FP-gamma-GS). Inhibition of FP-gamma-GS is
      not directly due to trimethoprim. Instead, it arises from accumulation of DHFR's
      substrate dihydrofolate, which we show is a potent FP-gamma-GS inhibitor. Thus,
      owing to the inherent connectivity of the metabolic network, falling DHFR
      activity leads to falling FP-gamma-GS activity in a domino-like cascade. This
      cascade results in complex folate dynamics, and its incorporation in a
      computational model of folate metabolism recapitulates the dynamics observed
      experimentally. These results highlight the potential for quantitative analysis
      of cellular metabolism to reveal mechanisms of drug action.

PMID- 18724368
TI  - MYO5B mutations cause microvillus inclusion disease and disrupt epithelial cell
      polarity.
AB  - Following homozygosity mapping in a single kindred, we identified nonsense and
      missense mutations in MYO5B, encoding type Vb myosin motor protein, in
      individuals with microvillus inclusion disease (MVID). MVID is characterized by
      lack of microvilli on the surface of enterocytes and occurrence of intracellular
      vacuolar structures containing microvilli. In addition, mislocalization of
      transferrin receptor in MVID enterocytes suggests that MYO5B deficiency causes
      defective trafficking of apical and basolateral proteins in MVID.

PMID- 18724371
TI  - Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to
      promote T cell cytotoxicity.
AB  - The acquisition of cytotoxic effector function by CD8(+) T cells is crucial for
      the control of intracellular infection and tumor invasion. However, it remains
      unclear which signaling pathways are required for the differentiation of CD8(+)
      cytotoxic T lymphocytes. We show here that Notch2-deficient T cells had impaired
      differentiation into cytotoxic T lymphocytes. In addition, dendritic cells with
      lower expression of the Notch ligand Delta-like 1 induced the differentiation of
      cytotoxic T lymphocytes less efficiently. We found that the intracellular domain
      of Notch2 interacted with a phosphorylated form of the transcription factor
      CREB1, and together these proteins bound the transcriptional coactivator p300 to
      form a complex on the promoter of the gene encoding granzyme B. Our results
      suggest that the highly regulated, dynamic control of T cell cytotoxicity depends
      on the integration of Notch2 and CREB1 signals.

PMID- 18724372
TI  - Critical function for Naip5 in inflammasome activation by a conserved carboxy
      terminal domain of flagellin.
AB  - Inflammasomes are cytosolic multiprotein complexes that sense microbial infection
      and trigger cytokine production and cell death. However, the molecular components
      of inflammasomes and what they sense remain poorly defined. Here we demonstrate
      that 35 amino acids of the carboxyl terminus of flagellin triggered inflammasome
      activation in the absence of bacterial contaminants or secretion systems. To
      further elucidate the host flagellin-sensing pathway, we generated mice deficient
      in the intracellular sensor Naip5. These mice failed to activate the inflammasome
      in response to the 35 amino acids of flagellin or in response to Legionella
      pneumophila infection. Our data clarify the molecular basis for the cytosolic
      response to flagellin.

PMID- 18724374
TI  - Small functional groups for controlled differentiation of hydrogel-encapsulated
      human mesenchymal stem cells.
AB  - Cell-matrix interactions have critical roles in regeneration, development and
      disease. The work presented here demonstrates that encapsulated human mesenchymal
      stem cells (hMSCs) can be induced to differentiate down osteogenic and adipogenic
      pathways by controlling their three-dimensional environment using tethered small
      molecule chemical functional groups. Hydrogels were formed using sufficiently low
      concentrations of tether molecules to maintain constant physical characteristics,
      encapsulation of hMSCs in three dimensions prevented changes in cell morphology,
      and hMSCs were shown to differentiate in normal growth media, indicating that the
      small-molecule functional groups induced differentiation. To our knowledge, this
      is the first example where synthetic matrices are shown to control induction of
      multiple hMSC lineages purely through interactions with small-molecule chemical
      functional groups tethered to the hydrogel material. Strategies using simple
      chemistry to control complex biological processes would be particularly powerful
      as they could make production of therapeutic materials simpler, cheaper and more
      easily controlled.

PMID- 18724373
TI  - Sensing of 'danger signals' and pathogen-associated molecular patterns defines
      binary signaling pathways 'upstream' of Toll.
AB  - In drosophila, molecular determinants from fungi and Gram-positive bacteria are
      detected by circulating pattern-recognition receptors. Published findings suggest
      that such pattern-recognition receptors activate as-yet-unidentified serine
      protease cascades that culminate in the cleavage of Spatzle, the endogenous Toll
      receptor ligand, and trigger the immune response. We demonstrate here that the
      protease Grass defines a common activation cascade for the detection of fungi and
      Gram-positive bacteria mediated by pattern-recognition receptors. The serine
      protease Persephone, shown before to be specific for fungal detection in a
      cascade activated by secreted fungal proteases, was also required for the sensing
      of proteases elicited by bacteria in the hemolymph. Hence, Persephone defines a
      parallel proteolytic cascade activated by 'danger signals' such as abnormal
      proteolytic activities.

PMID- 18724375
TI  - Highly compressed ammonia forms an ionic crystal.
AB  - Ammonia is an important compound with many uses, such as in the manufacture of
      fertilizers, explosives and pharmaceuticals. As an archetypal hydrogen-bonded
      system, the properties of ammonia under pressure are of fundamental interest, and
      compressed ammonia has a significant role in planetary physics. We predict new
      high-pressure crystalline phases of ammonia (NH(3)) through a computational
      search based on first-principles density-functional-theory calculations. Ammonia
      is known to form hydrogen-bonded solids, but we predict that at higher pressures
      it will form ammonium amide ionic solids consisting of alternate layers of
      NH(4)(+) and NH(2)(-) ions. These ionic phases are predicted to be stable over a
      wide range of pressures readily obtainable in laboratory experiments. The
      occurrence of ionic phases is rationalized in terms of the relative ease of
      forming ammonium and amide ions from ammonia molecules, and the volume reduction
      on doing so. We also predict that the ionic bonding cannot be sustained under
      extreme compression and that, at pressures beyond the reach of current static
      loading experiments, ammonia will return to hydrogen-bonded structures consisting
      of neutral NH(3) molecules.

PMID- 18724376
TI  - An efficient and versatile system for acute and chronic modulation of renal
      tubular function in transgenic mice.
AB  - We describe a transgenic mouse line, Pax8-rtTA, which, under control of the mouse
      Pax8 promoter, directs high levels of expression of the reverse tetracycline
      dependent transactivator (rtTA) to all proximal and distal tubules and the entire
      collecting duct system of both embryonic and adult kidneys. Using crosses of Pax8
      rtTA mice with tetracycline-responsive c-MYC mice, we established a new,
      inducible model of polycystic kidney disease that can mimic adult onset and that
      shows progression to renal malignant disease. When targeting the expression of
      transforming growth factor beta-1 to the kidney, we avoided early lethality by
      discontinuous treatment and successfully established an inducible model of renal
      fibrosis. Finally, a conditional knockout of the gene encoding tuberous sclerosis
      complex-1 was achieved, which resulted in the early outgrowth of giant polycystic
      kidneys reminiscent of autosomal recessive polycystic kidney disease. These
      experiments establish Pax8-rtTA mice as a powerful tool for modeling renal
      diseases in transgenic mice.

PMID- 18724377
TI  - Brain-type creatine kinase has a crucial role in osteoclast-mediated bone
      resorption.
AB  - Osteoclasts differentiate from precursor cells of the monocyte-macrophage lineage
      and subsequently become activated to be competent for bone resorption through
      programs primarily governed by receptor activator of nuclear factor-kappaB ligand
      in cooperation with macrophage colony-stimulating factor. Proteins prominently
      expressed at late phases of osteoclastogenesis and with a supportive role in
      osteoclast function are potential therapeutic targets for bone-remodeling
      disorders. In this study, we used a proteomics approach to show that abundance of
      the brain-type cytoplasmic creatine kinase (Ckb) is greatly increased during
      osteoclastogenesis. Decreasing Ckb abundance by RNA interference or blocking its
      enzymatic activity with a pharmacological inhibitor, cyclocreatine, suppressed
      the bone-resorbing activity of osteoclasts grown in vitro via combined effects on
      actin ring formation, RhoA GTPase activity and vacuolar ATPase function.
      Activities of osteoclasts derived from Ckb-/- mice were similarly affected. In
      vivo studies showed that Ckb-/- mice were better protected against bone loss
      induced by ovariectomy, lipopolysaccharide challenge or interleukin-1 treatment
      than wild-type controls. Furthermore, administration of cyclocreatine or
      adenoviruses harboring Ckb small hairpin RNA attenuated bone loss in rat and
      mouse models. Our findings establish an important role for Ckb in the bone
      resorbing function of osteoclasts and underscore its potential as a new molecular
      target for antiresorptive drug development.

PMID- 18724378
TI  - RPN2 gene confers docetaxel resistance in breast cancer.
AB  - Drug resistance acquired by cancer cells has led to treatment failure. To
      understand the regulatory network underlying docetaxel resistance in breast
      cancer cells and to identify molecular targets for therapy, we tested small
      interfering RNAs (siRNAs) against 36 genes whose expression was elevated in human
      nonresponders to docetaxel for the ability to promote apoptosis of docetaxel
      resistant human breast cancer cells (MCF7-ADR cells). The results indicate that
      the downregulation of the gene encoding ribophorin [corrected] II (RPN2), which
      is part of an N-oligosaccharyl transferase complex, most efficiently induces
      apoptosis of MCF7-ADR cells in the presence of docetaxel. RPN2 silencing induced
      reduced glycosylation of the P-glycoprotein, as well as decreased membrane
      localization, thereby sensitizing MCF7-ADR cells to docetaxel. Moreover, in vivo
      delivery of siRNA specific for RPN2 markedly reduced tumor growth in two types of
      models for drug resistance. Thus, RPN2 silencing makes cancer cells
      hypersensitive response to docetaxel, and RPN2 might be a new target for RNA
      interference-based therapeutics against drug resistance.

PMID- 18724379
TI  - The actin cytoskeleton of kidney podocytes is a direct target of the
      antiproteinuric effect of cyclosporine A.
AB  - The immunosuppressive action of the calcineurin inhibitor cyclosporine A (CsA)
      stems from the inhibition of nuclear factor of activated T cells (NFAT) signaling
      in T cells. CsA is also used for the treatment of proteinuric kidney diseases. As
      it stands, the antiproteinuric effect of CsA is attributed to its
      immunosuppressive action. Here we show that the beneficial effect of CsA on
      proteinuria is not dependent on NFAT inhibition in T cells, but rather results
      from the stabilization of the actin cytoskeleton in kidney podocytes. CsA blocks
      the calcineurin-mediated dephosphorylation of synaptopodin, a regulator of Rho
      GTPases in podocytes, thereby preserving the phosphorylation-dependent
      synaptopodin-14-3-3 beta interaction. Preservation of this interaction, in turn,
      protects synaptopodin from cathepsin L-mediated degradation. These results
      represent a new view of calcineurin signaling and shed further light on the
      treatment of proteinuric kidney diseases. Novel calcineurin substrates such as
      synaptopodin may provide promising starting points for antiproteinuric drugs that
      avoid the serious side effects of long-term CsA treatment.

PMID- 18724381
TI  - Pharmacology of the short QT syndrome N588K-hERG K+ channel mutation:
      differential impact on selected class I and class III antiarrhythmic drugs.
AB  - BACKGROUND AND PURPOSE: The short QT syndrome (SQTS) is associated with cardiac
      arrhythmias and sudden death. The SQT1 form of SQTS results from an inactivation
      attenuated, gain-of-function mutation (N588K) to the human ether-a-go-go-related
      gene (hERG) potassium channel. Pharmacological blockade of this mutated hERG
      channel may have therapeutic value. However, hERG-blocking potencies of canonical
      inhibitors such as E-4031 and D-sotalol are significantly reduced for N588K-hERG.
      Here, five hERG-blocking drugs were compared to determine their relative
      potencies for inhibiting N588K channels, and two other inactivation-attenuated
      mutant channels were tested to investigate the association between impaired
      inactivation and altered drug potency. EXPERIMENTAL APPROACH: Whole-cell patch
      clamp measurements of hERG current (I(hERG)) mediated by wild-type and mutant
      (N588K, S631A and N588K/S631A) channels were made at 37 degrees C CHO cells. KEY
      RESULTS: The N588K mutation attenuated I(hERG) inhibition in the following order:
      E-4031>amiodarone>quinidine>propafenone>disopyramide. Comparing the three
      inactivation mutants, the two single mutations, although occurring in different
      modules of the channel, attenuated inactivation to a nearly identical degree,
      whereas the double mutant caused considerably greater attenuation, permitting the
      titration of inactivation. Attenuation of channel inhibition was similar between
      the single mutants for each drug, and was significantly greater with the double
      mutant. CONCLUSIONS AND IMPLICATIONS: The degree of drug inhibition of hERG
      channels may vary based on the level of channel inactivation. Drugs previously
      identified as useful for treating SQT1 have the least dependence on hERG
      inactivation. In addition, our findings indicate that amiodarone may warrant
      further investigation as a potential treatment for SQT1.

PMID- 18724382
TI  - Effect of hypouricaemic and hyperuricaemic drugs on the renal urate efflux
      transporter, multidrug resistance protein 4.
AB  - BACKGROUND AND PURPOSE: The xanthine oxidase inhibitors allopurinol and
      oxypurinol are used to treat hyperuricaemia, whereas loop and thiazide diuretics
      can cause iatrogenic hyperuricaemia. Some uricosuric drugs and salicylate have a
      bimodal action on urate renal excretion. The mechanisms of action of these hypo-
      and hyperuricaemic drugs on the handling of urate in renal tubules have not been
      fully elucidated. Recently, we identified the multidrug resistance protein (MRP)
      4 as a luminal efflux transporter for urate in the proximal tubule. EXPERIMENTAL
      APPROACH: Here, we studied the effect of these drugs on [(14)C]urate transport
      using human embryonic kidney 293 cells overexpressing human MRP4 and in membrane
      vesicles isolated from these cells. KEY RESULTS: Allopurinol stimulated MRP4
      mediated cellular urate efflux and allopurinol and oxypurinol both markedly
      stimulated urate transport by MRP4 in membrane vesicles. Bumetanide and
      torasemide had no effect, whereas furosemide, chlorothiazide,
      hydrochlorothiazide, salicylate, benzbromarone and sulfinpyrazone inhibited urate
      transport, at concentrations ranging from nanomolar up to millimolar. Probenecid
      stimulated urate transport at 0.1 microM and inhibited transport at higher
      concentrations. CONCLUSIONS AND IMPLICATIONS: These data suggest that inhibition
      of MRP4-mediated urate efflux by furosemide and thiazide diuretics could have an
      important function in their hyperuricaemic mechanisms. Furthermore, stimulation
      of MRP4-mediated renal urate efflux could be a new mechanism in the hypouricaemic
      action of allopurinol and oxypurinol. In conclusion, MRP4 may provide a potential
      target for drugs affecting urate homoeostasis, which needs to be further
      evaluated in vivo.

PMID- 18724383
TI  - Human embryonic stem cells and lung regeneration.
AB  - Human embryonic stem cells are pluripotent cells derived from the inner cell mass
      of preimplantation stage embryos. Their unique potential to give rise to all
      differentiated cell types has generated great interest in stem cell research and
      the potential that it may have in developmental biology, medicine and
      pharmacology. The main focus of stem cell research has been on cell therapy for
      pathological conditions with no current methods of treatment, such as
      neurodegenerative diseases, cardiac pathology, retinal dysfunction and lung and
      liver disease. The overall aim is to develop methods of application either of
      pure cell populations or of whole tissue parts to the diseased organ under
      investigation. In the field of pulmonary research, studies using human embryonic
      stem cells have succeeded in generating enriched cultures of type II pneumocytes
      in vitro. On account of their potential of indefinite proliferation in vitro,
      embryonic stem cells could be a source of an unlimited supply of cells available
      for transplantation and for use in gene therapy. Uncovering the ability to
      generate such cell types will expand our understanding of biological processes to
      such a degree that disease understanding and management could change
      dramatically.

PMID- 18724384
TI  - Differential enhancement of leukaemia cell differentiation without elevation of
      intracellular calcium by plant-derived sesquiterpene lactone compounds.
AB  - BACKGROUND AND PURPOSE: All-trans retinoic acid (ATRA) induces complete remission
      in a majority of acute promyelocytic leukaemia patients, but resistance of
      leukaemic cells to ATRA and its toxicity, such as hypercalcaemia, lead to a
      limitation of treatment. Therefore, combination therapies with differentiation
      enhancing agents at non-toxic concentrations of ATRA may overcome its side
      effects. Here, we investigated the effect of plant-derived sesquiterpene lactone
      compounds and their underlying mechanisms in ATRA-induced differentiation of
      human leukaemia HL-60 cells. EXPERIMENTAL APPROACH: HL-60 cells were treated with
      four sesquiterpene lactones (helenalin, costunolide, parthenolide and
      sclareolide) and cell differentiation was determined by NBT reduction, Giemsa and
      cytofluorometric analyses. Signalling pathways were assessed by western blotting,
      gel-shift assay and kinase activity determinations and intracellular calcium
      levels were determined using a calcium-specific fluorescent probe. KEY RESULTS:
      Helenalin, costunolide and parthenolide, but not sclareolide, increased ATRA
      induced HL-60 cell differentiation into a granulocytic lineage. Signalling
      kinases PKC and ERK were involved in the ATRA-induced differentiation enhanced by
      all of the effective sesquiterpene lactones, but JNK and PI3-K were involved in
      the ATRA-induced differentiation enhanced by costunolide and parthenolide.
      Enhancement of cell differentiation closely correlated with inhibition of NF
      kappaB DNA-binding activity by all three effective compounds. Importantly,
      enhancement of differentiation induced by 50 nM ATRA by the sesquiterpene
      lactones was not accompanied by elevation of basal intracellular calcium
      concentrations. CONCLUSIONS AND IMPLICATIONS: These results indicate that plant
      derived sesquiterpene lactones may enhance ATRA-mediated cell differentiation
      through distinct pathways.

PMID- 18724385
TI  - The antioxidant activity of chondroitin-4-sulphate, in carbon tetrachloride
      induced acute hepatitis in mice, involves NF-kappaB and caspase activation.
AB  - BACKGROUND AND PURPOSE: Reactive oxygen species (ROC) are the main causes of
      carbon tetrachloride (CCl4)-induced acute liver injury. Chondroitin-4-sulphate
      (C4S) is known to inhibit lipid peroxidation through antioxidant mechanisms.
      Activation of nuclear factor (NF)-kappaB and caspases may strongly intensify
      inflammation and cell damage, in addition to that directly exerted by ROS. We
      investigated whether treatment with C4S, besides exerting antioxidant activity,
      was able to modulate NF-kappaB and apoptosis activation in CCl4-induced liver
      injury in mice. EXPERIMENTAL APPROACH: Acute hepatitis was induced in mice by an
      i.p. injection of CCl(4). Varying doses of C4S were administered i.p. 1 h before,
      6 and 12 h after CCl4 injection. 24 h after CCl4 injection, the mice were killed
      for biochemical and histological analysis. KEY RESULTS: CCl4 injection produced:
      marked elevation of alanine aminotransferase and aspartate aminotransferase;
      hepatic membrane lipid peroxidation, assayed by 8-isoprostane levels; and
      depletion of reduced glutathione and superoxide dismutase. CCl4 also decreased NF
      kappaB translocation and IkBalpha, and increased gene expression of mRNA and
      protein of metalloproteases (MMP)-2 and -9, and of pro- and cleaved forms of
      caspases-3 and -7. There was also increased liver polymorphonuclear infiltration,
      evaluated by elastase assay, and hepatic cell disruption.C4S treatment inhibited
      lipid peroxidation; blocked NF-kappaB activation and IkBalpha protein loss;
      decreased mRNA and proteins for MMPs and caspases; restored endogenous
      antioxidants; limited hepatic polymorphonuclear accumulation and tissue damage.
      CONCLUSIONS AND IMPLICATIONS: As antioxidants may inhibit NF-kappaB and caspase
      activation, we hypothesize that treatment with C4S was able to inhibit NF-kappaB
      and apoptosis activation in hepatic injury.

PMID- 18724386
TI  - Endogenous and synthetic agonists of GPR119 differ in signalling pathways and
      their effects on insulin secretion in MIN6c4 insulinoma cells.
AB  - BACKGROUND AND PURPOSE: GPR119 is a G protein-coupled receptor that is
      preferentially expressed in islet cells and mediates insulin secretion. Oleoyl
      lysophosphatidylcholine and oleoylethanolamide (OEA) act as endogenous ligands
      for this receptor, whereas PSN375963 and PSN632408 are two recently reported
      synthetic agonists. In this study, we explored mechanisms underlying GPR119
      induced insulin secretion. In addition, we assessed the potential utility of the
      synthetic agonists as tools for exploring GPR119 biology. EXPERIMENTAL APPROACH:
      We examined natural and synthetic GPR119 agonist activity at GPR119 in MIN6c4 and
      RINm5f insulinoma cells. We evaluated insulin secretion, intracellular calcium
      [Ca(2+)](i), ion channel involvement and levels of cAMP. KEY RESULTS: We report
      that increases in insulin secretion induced by OEA were associated with increased
      cAMP and a potentiation of glucose-stimulated increases in [Ca(2+)](i). We also
      demonstrate that ATP-sensitive K(+) and voltage-dependent calcium channels were
      required for GPR119-mediated increases in glucose-stimulated insulin secretion.
      In contrast to OEA, the synthetic GPR119 agonist PSN375963 and PSN632408 have
      divergent effects on insulin secretion, cAMP and intracellular calcium in MIN6c4
      cells. CONCLUSIONS AND IMPLICATIONS: The endogenous ligand OEA signals through
      GPR119 in a manner similar to glucagon-like peptide-1 (GLP-1) and its receptor
      with respect to insulin secretion, [Ca(2+)](i) and cAMP. In addition, PSN375963
      and PSN632408 substantially differ from OEA and from one another. These studies
      suggest that the commercially available synthetic agonists, although they do
      activate GPR119, may also activate GPR119-independent pathways and are thus
      unsuitable as GPR119-specific pharmacological tools.

PMID- 18724387
TI  - Inhibition of fatty acid amide hydrolase produces PPAR-alpha-mediated analgesia
      in a rat model of inflammatory pain.
AB  - BACKGROUND AND PURPOSE: We have previously demonstrated antinociceptive effects
      of fatty acid amide hydrolase (FAAH) inhibition that were accompanied by
      increases in the levels of endocannabinoids (ECs) in the hind paw. Here, the
      effects of the FAAH inhibitor URB597 (3'-carbamoyl-biphenyl-3-yl
      cyclohexylcarbamate) on responses of spinal neurons were studied. EXPERIMENTAL
      APPROACH: Extracellular single-unit recordings of dorsal horn neurons were made
      in anaesthetized rats with hind paw inflammation induced by lambda-carrageenan.
      Effects of intraplantar pre-administration of URB597, or vehicle, on carrageenan
      evoked expansion of peripheral receptive fields of spinal neurons and
      mechanically evoked responses of neurons were studied. The cannabinoid receptor
      type 1 (CB(1)) antagonist AM251 (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4
      dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) and the peroxisome
      proliferator-activated receptor (PPAR)-alpha antagonist GW6471 ([(2S)-2-[[(1Z)-1
      methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl]amino]-3-[4-[2-(5-methyl-2
      phenyl-4-oxa zolyl)ethoxy]phenyl]propyl]-carbamic acid ethyl ester) were used to
      investigate the roles of these receptors in mediating the effects of URB597. KEY
      RESULTS: URB597 (25 microg in 50 microL) pretreatment significantly inhibited
      carrageenan-evoked receptive field expansion and this was significantly reversed
      by co-administration of the PPAR-alpha antagonist but not the CB(1) antagonist.
      Pretreatment with the PPAR-alpha receptor agonist WY14643 ([[4-chloro-6-[(2,3
      dimethylphenyl)amino]-2-pyrimidinyl]thio]acetic acid) also significantly
      inhibited receptive field expansion. URB597 (25 or 100 microg in 50 microL) had
      no significant effect on mechanically evoked responses of spinal neurons.
      CONCLUSIONS AND IMPLICATIONS: URB597 inhibited receptive field expansions but not
      mechanically evoked responses of spinal neurons in rats with hind paw
      inflammation. These effects were blocked by PPAR-alpha receptor antagonism. These
      data support the contention that URB597 exerts its antinociceptive effects by
      indirect inhibition of sensitization of neuronal responses at least partly
      through PPAR-alpha activation due to enhanced EC levels.

PMID- 18724389
TI  - The WW domain containing E3 ubiquitin protein ligase 1 upregulates ErbB2 and EGFR
      through RING finger protein 11.
AB  - The WW domain containing E3 ubiquitin protein ligase 1 (WWP1) is a homologous to
      the E6-associated protein C terminus-type E3 ligase frequently overexpressed in
      human prostate and breast cancers due to gene amplification. Previous studies
      suggest that WWP1 promotes cell proliferation and survival; however, the
      mechanism of WWP1 action is still poorly understood. Here, we showed that WWP1
      upregulates and maintains erythroblastic leukemia viral oncogene homolog 2
      (ErbB2) and epithelial growth factor receptor (EGFR) in multiple cell lines. WWP1
      depletion dramatically attenuates the EGF-induced ERK phosphorylation. WWP1 forms
      a protein complex with RING finger protein 11 (RNF11), a negative regulator of
      ErbB2 and EGFR. The protein-protein interaction is through the first and third WW
      domains of WWP1 and the PY motif of RNF11. Although WWP1 is able to ubiquitinate
      RNF11 in vitro and in vivo, WWP1 neither targets RNF11 for degradation nor
      changes RNF11's cellular localization. Importantly, inhibition of RNF11 can
      rescue WWP1 siRNA-induced ErbB2 and EGFR downregulation and growth arrest.
      Finally, we demonstrated that RNF11 is overexpressed in a panel of prostate and
      breast cancer cell lines with WWP1 expression. These findings suggest that WWP1
      may promote cell proliferation and survival partially through suppressing RNF11
      mediated ErbB2 and EGFR downregulation.

PMID- 18724388
TI  - Prostate tumor progression is mediated by a paracrine TGF-beta/Wnt3a signaling
      axis.
AB  - Transforming growth factor (TGF)-beta is an important paracrine factor in
      tumorigenesis. Ligand binding of the type I and II TGF-beta receptors initiate
      downstream signaling. The role of stromal TGF-beta signaling in prostate cancer
      progression is unknown. In mice, the conditional stromal knockout of the TGF-beta
      type II receptor expression (Tgfbr2(fspKO)) resulted in the development of
      prostatic intraepithelial neoplasia and progression to adenocarcinoma within 7
      months. Clinically, we observed a loss of TGF-beta receptor type II expression in
      69% of human prostate cancer-associated stroma, compared to 15% of stroma
      associated with benign tissues (n=140, P-value <0.0001). To investigate the
      mechanism of paracrine TGF-beta signaling in prostate cancer progression, we
      compared the effect of the prostatic stromal cells from Tgfbr2(fspKO) and floxed
      TGF-beta type II receptor Tgfbr2(floxE2/floxE2) mice on LNCaP human prostate
      cancer cells in vitro and tissue recombination xenografts. Induction of LNCaP
      cell proliferation and tumorigenesis was observed by Tgfbr2(fspKO) prostate
      stroma as a result of elevated Wnt3a expression. Neutralizing antibodies to Wnt3a
      reversed LNCaP tumorigenesis. The TGF-beta inhibition of Wnt3a expression was in
      part through the suppression of Stat3 activity on the Wnt3a promoter. In
      conclusion, the frequent loss of stromal TGF-beta type II receptor expression in
      human prostate cancer can relieve the paracrine suppression of Wnt3a expression.

PMID- 18724391
TI  - Nausea and vomiting with high-dose chemotherapy and stem cell rescue therapy: a
      review of antiemetic regimens.
AB  - Stem cell transplantation, using high-dose chemotherapy with or without TBI, is
      usually associated with significant nausea and vomiting. A variety of antiemetic
      regimens have been studied to control nausea and vomiting associated with the
      preparative therapy phase of SCT. We review the most significant studies and
      highlight the limitations of many of these studies. In addition, we review the
      few studies with the use of aprepitant as an antiemetic in combination with a
      5HT(3) antagonist and a steroid. The American Society of Clinical Oncology
      guideline for antiemetic use for treatment regimens that are highly emetogenic is
      reviewed regarding recommendations for SCT preparative regimens. On the basis of
      this review of published data, we recommend the basic outline for an effective
      antiemetic investigational approach to the study and to the control of nausea and
      vomiting during the preparative phase of treatment for SCT.

PMID- 18724390
TI  - Overlapping gene expression profiles of cell migration and tumor invasion in
      human bladder cancer identify metallothionein 1E and nicotinamide N
      methyltransferase as novel regulators of cell migration.
AB  - Cell migration is essential to cancer invasion and metastasis and is spatially
      and temporally integrated through transcriptionally dependent and independent
      mechanisms. As cell migration is studied in vitro, it is important to identify
      genes that both drive cell migration and are biologically relevant in promoting
      invasion and metastasis in patients with cancer. Here, gene expression profiling
      and a high-throughput cell migration system answers this question in human
      bladder cancer. In vitro migration rates of 40 microarray-profiled human bladder
      cancer cell lines were measured by radial migration assay. Genes whose expression
      was either directly or inversely associated with cell migration rate were
      identified and subsequently evaluated for their association with cancer stage in
      61 patients. This analysis identified genes known to be associated with cell
      invasion such as versican, and novel ones, including metallothionein 1E (MT1E)
      and nicotinamide N-methyltransferase (NNMT), whose expression correlated
      positively with cancer cell migration and tumor stage. Using loss of function
      analysis, we show that MT1E and NNMT are necessary for cancer cell migration.
      These studies provide a general approach to identify the clinically relevant
      genes in cancer cell migration and mechanistically implicate two novel genes in
      this process in human bladder cancer.

PMID- 18724392
TI  - Long-term lymphoid-restricted split chimerism after myeloablative allogeneic BMT
      for bcr-abl+ ALL.

PMID- 18724393
TI  - Outcome of second allogeneic transplants using reduced-intensity conditioning
      following relapse of haematological malignancy after an initial allogeneic
      transplant.
AB  - Disease relapse following an allogeneic transplant remains a major cause of
      treatment failure, often with a poor outcome. Second allogeneic transplant
      procedures have been associated with high TRM, especially with myeloablative
      conditioning. We hypothesized that the use of reduced-intensity conditioning
      (RIC) would decrease the TRM. We performed a retrospective national multicentre
      analysis of 71 patients receiving a second allogeneic transplant using RIC after
      disease relapse following an initial allogeneic transplant. The majority of
      patients had leukaemia/myelodysplasia (MDS) (N=57), nine had lymphoproliferative
      disorders, two had myeloma and three had myeloproliferative diseases. A total of
      25% of patients had unrelated donors. The median follow-up was 906 days from the
      second allograft. The predicted overall survival (OS) and TRM at 2 years were 28
      and 27%, respectively. TRM was significantly lower in those who relapsed late
      (>11 months) following the first transplant (2 years: 17 vs 38% in early
      relapses; P=0.03). Two factors were significantly associated with a better
      survival: late relapse (P=0.014) and chronic GVHD following the second transplant
      (P=0.014). These data support our hypothesis that the second RIC allograft
      results in a lower TRM than using MA. A proportion of patients achieved a
      sustained remission even when relapsing after a previous MA transplant.

PMID- 18724394
TI  - The harvest and use of autologous back-up grafts for graft failure or severe GVHD
      after allogeneic hematopoietic stem cell transplantation: a survey of the
      European Group for Blood and Marrow Transplantation.
AB  - Autologous hematopoietic stem cells (HSCs) harvested as back-up prior to
      allogeneic hematopoietic SCT (HSCT) may potentially be useful in the treatment of
      graft failure or in cases with severe GVHD. Here, we studied the general policies
      and indications for autologous back-up harvest among the European Group for Blood
      and Marrow Transplantation centers in the year 2003. The outcome of patients
      receiving autologous back-up transfusion between 1998 and 2002 was evaluated
      retrospectively. The responses from 94 centers showed that 48 centers had a
      general policy with variable indications for autologous back-up harvest. Thirty
      five patients with graft failure (25), GVHD (8) or relapse (2) retransplanted
      with autologous back-ups were reported. Autologous back-up transfusion was
      performed at a median of 35 days (patients with graft failure) or 90 days
      (patients with GVHD) after allogeneic HSCT. Within 100 days after autologous
      HSCT, 21 patients died from treatment-related complications (19) or relapse (2).
      Estimated overall survival at 1 year was 16% (95% CI 0-32%) for patients treated
      for graft failure and 13% (95% CI 0-37%) for GVHD patients. In conclusion, our
      data demonstrate that the indication for autologous back-up harvests is limited
      and that general storage and use cannot be recommended unless in selected
      prospective studies.

PMID- 18724395
TI  - Combination of CsA, MTX and low-dose, short-course mycophenolate mofetil for GVHD
      prophylaxis.
AB  - In an effort to reduce the incidence and severity of acute GVHD (aGVHD), we have
      developed a new prophylaxis regimen combining cyclosporine and MTX with a short
      30-day course of low-dose (500 mg per day) mycophenolate mofetil. This regimen
      was studied prospectively 100 patients undergoing HLA-matched and 1-antigen
      mismatched allogeneic peripheral blood SCT from related donors. The cumulative
      incidence of aGVHD was 16% (grades II-IV (9.5%) and grades III-IV (1%)). The
      cumulative incidence of chronic GVHD (cGVHD) was 53% with 28% extensive cGVHD.
      The cumulative incidence of transplant-related mortality at 100 days and 3 years
      were 6 and 13%. The estimated probabilities of disease-free survival at 3 years
      in standard- and high-risk patients were 77 and 30%, respectively (P<0.0001). The
      estimated probabilities of overall survival at 3 years in standard- and high-risk
      patients were 77 and 37%, respectively (P<0.0001). These data show a substantial
      decrease in the risk of developing aGVHD without an increase in relapse or any
      adverse impact on survival in standard-risk patients.

PMID- 18724396
TI  - Influenza vaccination in hematopoietic SCT recipients.
AB  - Influenza is a potentially serious infection after hematopoietic SCT (HSCT).
      Vaccination is the main prophylactic approach in individuals at an increased risk
      for severe influenza disease or post-influenza complications. No controlled study
      on the efficacy of influenza vaccination has been performed in HSCT recipients
      and also studies evaluating the antibody response are limited by their small
      sizes and by that vaccinations have been performed at varying times after HSCT.
      The reports show that serological response rates are lower in HSCT patients than
      in healthy individuals. However, patients receiving influenza vaccine at 6 months
      or later after HSCT have a lower risk for virological confirmed influenza. The
      documentation for efficacy if patients are vaccinated earlier than 6 months after
      HSCT is mostly lacking but it has been shown that T-cell responses can be
      elicited after vaccination. Therefore, currently available recommendations
      suggest starting earlier when the risk for influenza is high, especially during
      ongoing community outbreaks. Two vaccine doses are recommended in children below
      the age of 9 years, who have not been previously vaccinated against influenza.
      Vaccination of family members, close contacts and health-care workers is
      recommended.

PMID- 18724397
TI  - High prevalence of metabolic syndrome after allogeneic hematopoietic cell
      transplantation.
AB  - We conducted a cross-sectional study to estimate the prevalence of metabolic
      syndrome, a clustering of risk factors associated with cardiovascular disease,
      among 86 adults who had allogeneic hematopoietic-cell transplant (HCT) as
      compared with 258 age- and gender-matched US population controls selected from
      the 2005-2006 National Health and Nutrition Examination Survey database. The
      median age at study enrollment was 50 years (range, 21-71), and patients were at
      a median of 3 years (range, 1-21) from HCT. The prevalence of metabolic syndrome
      was 49% (95% confidence intervals (CI), 38-60%) among HCT recipients, a 2.2-fold
      (95% CI, 1.3-3.6, P=0.002) increase compared with controls. The prevalence rates
      of elevated blood pressure and hypertriglyceridemia were significantly higher
      among HCT recipients than among controls, but the prevalence rates of abdominal
      obesity, elevated blood glucose and low high-density lipoprotein cholesterol were
      not. HCT survivors with metabolic syndrome were more likely to have
      microalbuminuria (43 vs 10%) and elevated creatinine (31 vs 11%). No patient,
      donor or transplant characteristics were associated with the diagnosis of
      metabolic syndrome. We conclude that metabolic syndrome occurs frequently among
      allogeneic HCT survivors who are seen by transplant physicians. Approaches to
      screening, prevention and management of metabolic syndrome should be developed
      for HCT recipients.

PMID- 18724398
TI  - Chances and pitfalls of chemical cross-linking with amine-reactive N
      hydroxysuccinimide esters.
AB  - In this report we summarize our experiences with the reaction products of N
      hydroxysuccinimide (NHS) esters, which are widely used for chemical cross-linking
      of lysine residues in proteins. We describe the products, which should be
      scrutinized during data analysis using customized software when NHS esters are
      employed for chemical cross-linking. Reaction products of NHS esters were
      observed not only with lysines, but also with serines, tyrosines, and threonines.
      This report is intended to be a practical guide for those working in the field of
      chemical cross-linking and mass spectrometry.

PMID- 18724399
TI  - Unilateral diaphragmatic paralysis and segmental motor paresis following herpes
      zoster.
AB  - We report the case of a 73-year-old woman who complained of acute onset of pain
      and weakness of her left shoulder and proximal arm muscles 3 weeks after a
      diagnosis of herpes zoster. Electromyography revealed involvement of the C5-6
      myotomes and the upper trunk of the brachial plexus. Chest X-ray and
      electromyographic studies documented paralysis of the left diaphragm. One year
      after onset, muscle strength returned to normal, but radiographic and
      electrophysiologic findings of diaphragm paralysis were unchanged.

PMID- 18724400
TI  - The hepatopulmonary syndrome.

PMID- 18724401
TI  - The hepatopulmonary syndrome.

PMID- 18724402
TI  - Osteoporosis in men.

PMID- 18724403
TI  - Osteoporosis in men.

PMID- 18724404
TI  - A dichotic listening study of attention control in older adults.
AB  - The influence of age on attentional control of bottom-up processing was
      investigated with a dichotic-listening paradigm. The typical right-ear-advantage
      (REA) without specific attentional instructions was used as a measure of bottom
      up processing (non-forced condition). Top-down attentional control was evaluated
      by instructing subjects to report only the right or left ear stimulus of the
      dichotic pair (forced-right, forced-left conditions). Both young and old
      participants showed a REA in the non-forced condition and an increased REA in the
      forced-right condition. The old group failed, however, to use attention to
      modulate the REA to the same degree as the younger participants in the forced
      left condition. Only the young group showed a significant left ear advantage
      (LEA). The results are discussed in relation to cognitive decline in normal aging
      and in early stages of dementia.

PMID- 18724405
TI  - Diagnosis: pituitary gigantism in a 2 1/2-year old child.

PMID- 18724406
TI  - Epidemiology.

PMID- 18724407
TI  - Reply to Blazer et al.: flawed challenges to "Acetylcholinesterase inhibitors and
      Gulf War illnesses".

PMID- 18724408
TI  - Potassium transport and plant salt tolerance.
AB  - Salinity is a major abiotic stress affecting approximately 7% of the world's
      total land area resulting in billion dollar losses in crop production around the
      globe. Recent progress in molecular genetics and plant electrophysiology suggests
      that the ability of a plant to maintain a high cytosolic K+/Na+ ratio appears to
      be critical to plant salt tolerance. So far, the major efforts of plant breeders
      have been aimed at improving this ratio by minimizing Na+ uptake and transport to
      shoot. In this paper, we discuss an alternative approach, reviewing the molecular
      and ionic mechanisms contributing to potassium homeostasis in salinized plant
      tissues and discussing prospects for breeding for salt tolerance by targeting
      this trait. Major K+ transporters and their functional expression under saline
      conditions are reviewed and the multiple modes of their control are evaluated,
      including ameliorative effects of compatible solutes, polyamines and supplemental
      calcium. Subsequently, the genetic aspects of inheritance of K+ transport
      'markers' are discussed in the general context of salt tolerance as a polygenic
      trait. The molecular identity of 'salt tolerance' genes is analysed, and
      prospects for future research and breeding are examined.

PMID- 18724409
TI  - Role of magnesium in carbon partitioning and alleviating photooxidative damage.
AB  - Magnesium (Mg) deficiency exerts a major influence on the partitioning of dry
      matter and carbohydrates between shoots and roots. One of the very early
      reactions of plants to Mg deficiency stress is the marked increase in the shoot
      to-root dry weight ratio, which is associated with a massive accumulation of
      carbohydrates in source leaves, especially of sucrose and starch. These higher
      concentrations of carbohydrates in Mg-deficient leaves together with the
      accompanying increase in shoot-to-root dry weight ratio are indicative of a
      severe impairment in phloem export of photoassimilates from source leaves.
      Studies with common bean and sugar beet plants have shown that Mg plays a
      fundamental role in phloem loading of sucrose. At a very early stage of Mg
      deficiency, phloem export of sucrose is severely impaired, an effect that occurs
      before any noticeable changes in shoot growth, Chl concentration or
      photosynthetic activity. These findings suggest that accumulation of
      carbohydrates in Mg-deficient leaves is caused directly by Mg deficiency stress
      and not as a consequence of reduced sink activity. The role of Mg in the phloem
      loading process seems to be specific; resupplying Mg for 12 or 24 h to Mg
      deficient plants resulted in a very rapid recovery of sucrose export. It appears
      that the massive accumulation of carbohydrates and related impairment in
      photosynthetic CO2 fixation in Mg-deficient leaves cause an over-reduction in the
      photosynthetic electron transport chain that potentiates the generation of highly
      reactive O2 species (ROS). Plants respond to Mg deficiency stress by marked
      increases in antioxidative capacity of leaves, especially under high light
      intensity, suggesting that ROS generation is stimulated by Mg deficiency in
      chloroplasts. Accordingly, it has been found that Mg-deficient plants are very
      susceptible to high light intensity. Exposure of Mg-deficient plants to high
      light intensity rapidly induced leaf chlorosis and necrosis, an outcome that was
      effectively delayed by partial shading of the leaf blade, although the Mg
      concentrations in different parts of the leaf blade were unaffected by shading.
      The results indicate that photooxidative damage contributes to development of
      leaf chlorosis under Mg deficiency, suggesting that plants under high-light
      conditions have a higher physiological requirement for Mg. Maintenance of a high
      Mg nutritional status of plants is, thus, essential in the avoidance of ROS
      generation, which occurs at the expense of inhibited phloem export of sugars and
      impairment of CO2 fixation, particularly under high-light conditions.

PMID- 18724410
TI  - Heritabilities of copper-accumulating traits in Labrador retrievers.

PMID- 18724411
TI  - A new case of centric fusion in cattle: rob(21;23).

PMID- 18724412
TI  - A phosducin (PDC ) gene mutation does not cause progressive retinal atrophy in
      Korean miniature schnauzers.

PMID- 18724413
TI  - Beneficial effects of potassium on human health.
AB  - Until recently, humans consumed a diet high in potassium. However, with the
      increasing consumption of processed food, which has potassium removed, combined
      with a reduction in the consumption of fruits and vegetables, there has been a
      large decrease in potassium intake which now, in most developed countries,
      averages around 70 mmol day-1, i.e. only one third of our evolutionary intake.
      Much evidence shows that increasing potassium intake has beneficial effects on
      human health. Epidemiological and clinical studies show that a high-potassium
      diet lowers blood pressure in individuals with both raised blood pressure and
      average population blood pressure. Prospective cohort studies and outcome trials
      show that increasing potassium intake reduces cardiovascular disease mortality.
      This is mainly attributable to the blood pressure-lowering effect and may also be
      partially because of the direct effects of potassium on the cardiovascular
      system. A high-potassium diet may also prevent or at least slow the progression
      of renal disease. An increased potassium intake lowers urinary calcium excretion
      and plays an important role in the management of hypercalciuria and kidney stones
      and is likely to decrease the risk of osteoporosis. Low serum potassium is
      strongly related to glucose intolerance, and increasing potassium intake may
      prevent the development of diabetes that occurs with prolonged treatment with
      thiazide diuretics. Reduced serum potassium increases the risk of lethal
      ventricular arrhythmias in patients with ischaemic heart disease, heart failure
      and left ventricular hypertrophy, and increasing potassium intake may prevent
      this. The best way to increase potassium intake is to increase the consumption of
      fruits and vegetables.

PMID- 18724415
TI  - Significant colonic neoplasia prevalence and ASGE recommendations: is it time for
      a change?
AB  - GOALS AND BACKGROUND: To Evaluate the indications versus diagnostic yield of
      significant colonic neoplasia (SCN) in the open-access era and screening
      colonoscopy. STUDY: During 6-year period, all procedural data were obtained from
      all consecutive patients who underwent colonoscopies. Indications were compared
      with American Society for Gastrointestinal Endoscopy guidelines. RESULTS: In all
      22,341 procedures were included in the study. Indications were divided into 3
      groups: Screening (21.89% of the procedures), surveillance (17.60%) and
      symptoms/signs (60.51%). A total of 2867 patients (12.83%) had SCNs. Of these,
      278 (7.00%) SCNs were found in the group less than 50 years of age and 2589 in
      the group over the age of 50 years (14.10%). SCN as per indication frequency was
      12.69% in the symptom/sign group (subdivided to 7.24% and 14.01% in the under 50
      and over 50, age groups, respectively); screening 13.37% (5.48% and 15.09%,
      respectively); surveillance 12.64% (8.48% and 13.19%, respectively). The
      indications leading to the highest SCN rate (over 25%) were: abnormal imaging,
      elevated carcinoembryonic antigen, and rectal pain. CONCLUSIONS: Colonoscopy is a
      unique screening tool that can detect neoplastic lesions. SCN prevalence in our
      study was between 13% and 15% for all indications in patients above 50 years of
      age. This emphasizes performing a screening colonoscopy for the entire population
      over the age of 50 years, regardless of the indication. We feel that American
      Society for Gastrointestinal Endoscopy guidelines should be reassessed. The
      revised criteria should state that the primary indication, are all people over
      the age of 50 years, who should have a colonoscopy performed, unless otherwise
      contraindicated.

PMID- 18724416
TI  - [Experimental hemorrhagic stroke].
AB  - The authors propose the technique of experimental haemorrhagic stroke of a
      hypertensive type in non-narcotized rats produced by means of gravity overload in
      the caudocranial vector with the use of a special centrifuge.

PMID- 18724414
TI  - Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA
      prime-protein boost HIV-1 vaccine in healthy human volunteers.
AB  - An optimally effective AIDS vaccine would likely require the induction of both
      neutralizing antibody and cell-mediated immune responses, which has proven
      difficult to obtain in previous clinical trials. Here we report on the induction
      of human immunodeficiency virus type-1 (HIV-1)-specific immune responses in
      healthy adult volunteers that received the multi-gene, polyvalent, DNA prime
      protein boost HIV-1 vaccine formulation, DP6-001, in a Phase I clinical trial.
      Robust cross-subtype HIV-1 specific T cell responses were detected in IFN-gamma
      ELISPOT assays. Furthermore, we detected high titer serum antibody responses that
      recognized a wide range of primary HIV-1 Env antigens and also neutralized
      pseudotyped viruses that express the primary Env antigens from multiple HIV-1
      subtypes. These findings demonstrate that the DNA prime-protein boost approach is
      an effective immunization method to elicit both humoral and cell-mediated immune
      responses in humans, and that a polyvalent Env formulation could generate broad
      immune responses against HIV-1 viruses with diverse genetic backgrounds.

PMID- 18724417
TI  - [Rheology, hemolysis and peripheral blood indices in macaccus rhesus monkeys in
      health and posthemorrhagic period].
AB  - Twenty monkeys (macaccus rhesus) were examined by the following parameters:
      deformability of erythrocytes and mononuclear leukocytes, hemolytic activity of
      the serum, free hemoglobin of the serum and viscosity of plasma. The data
      obtained are accepted as standard because literature data on hemorrheology of
      monkeys are absent. Compared to relevant indices in humans, monkeys have
      increased hematocrit, serum hemolytic activity, erythrocytic rigidity index.
      Seven monkeys were used as the model of "donor" (6-8% blood loss). The above
      indices were measured before exfusion and on days 2, 7, 14 and 21 after exfusion.
      Maximal changes in rheology and hemolysis were observed on day 2 and 7 after
      blood loss which correlated with deviations of the red sprout of hemogeny.

PMID- 18724418
TI  - [Changes in oral mucosa microcirculation during adaptation to dentures in
      patients with complete anodontia].

PMID- 18724419
TI  - [Activation of cerebral antioxidant mechanisms in electric stimulation of the
      paleocerebellar cortex].
AB  - Electrical stimulations (ES, 100 Hz) of the paleocerebellar cortex (Iuvula and
      flocculus) were performed in male Wistar rats. Similar stimulations of the
      frontal cortical zones were used as control. Lipid peroxidation intensity was
      estimated spectrophotometrically by the level of products reacting with
      thiobarbituric acid. It is shown that ES of the cerebellar cortex caused a
      decrease of the above products in the brain hemispheres. Increased absorption of
      14C methionine by ventral hippocampal structures and 3H triptophane by ventral
      hippocampus, brain stem and the "rest" tissue of the brain was registered in
      response to electrostimulations. The findings are discussed in terms of
      activation of antioxidant mechanisms in brain structures.

PMID- 18724420
TI  - [Biomechanical assessment and morphofunctional changes in skin structures in
      pathogenesis of wound process].

PMID- 18724421
TI  - [Chromosome 17 abnormalities in medulloblastomas and their prognostic value].
AB  - The cytogenetic profile of chromosome 17 was studied in 180 medlloblastomas by
      the interphasic FISH technique, which revealed the high incidence of this
      aberration and its association with the poor clinical course of the disease. The
      interphasic cytogenetic analysis of chromosome 17 abnormalities in
      medulloblastoma biopsy specimens may be recommended for its inclusion into a
      complex of laboratory diagnostic methods used in the examination of these tumors.

PMID- 18724422
TI  - [Hemispherotomy in the treatment of drug-resistant symptomatic epilepsy in
      patients with Rasmussen's encephalitis].

PMID- 18724423
TI  - [Successful endovascular treatment for orbital varix: case report and literature
      review].
AB  - The pathogenesis and clinical manifestations of orbital varix and choice of its
      surgical treatment are described. Complete occlusion of abnormal portions of the
      superior ophthalmic vein with preserved blood flow along the main trunk is a
      specific feature of this observation. By analyzing the data available in the
      literature and their clinical observation of successful endovascular treatment
      for orbital varix with a complete regression of its clinical symptoms, the
      authors substantiate indications for transvenous orbital varix occlusion.

PMID- 18724424
TI  - [Intramedullary abscess of spinal cord as a complication of existing dermal
      sinus].
AB  - The paper describes a rare case of intramedullary spinal cord abscess in an
      infant after dermal sinus. In discussion with literature review the contemporary
      approach to patients with this pathology is highlighted.

PMID- 18724425
TI  - [Modern classification approach to central nervous system tumors].
AB  - Central nervous system (CNS) tumors cannot be, for a number of reasons,
      organically included into the existing tumor classification system - TNM. This
      hampers the registration and systematization of CNS tumors, the acquisition of
      valid data on their prevalence, and the organization of treatment in patients
      with CNS tumors. A variant of a classification of CNS tumors is proposed, which
      takes into account the specific features of this group of neoplasms.

PMID- 18724426
TI  - [C-reactive protein is a vector of fatty acid transfer to the cells that directly
      realize the systemic inflammatory response syndrome].

PMID- 18724427
TI  - [Saliva in clinical laboratory diagnosis (a review of literature)].

PMID- 18724428
TI  - [Analytical characteristics micromatrix semiquantitative method used in serial
      tests with video digital registration].
AB  - A multiplex analytical system has been developed to carry out microformat latex
      agglutination tests with video digital registration. The system makes it possible
      to apply less than 1 microl drops of latex and samples in the matrix format to a
      carrier and to make the test in 30 points at once, as well as to record and to
      interpret the results of the test, by keeping analytical information for each
      sample. Comparison of the results of determination of the serum levels of C
      reactive protein, rheumatoid factor, and antistreptolysine in the system
      developed by the authors with the results obtained in the macroagglutination test
      by the immunoturbidimetric technique leads to the conclusion that the methods are
      comparable. The proposed type of a latex agglutination test based on a matrix
      approach and miniaturization assures efficient production and the quality of
      laboratory studies.

PMID- 18724429
TI  - [Criteria for intoxication in the evaluation of severity of endotoxicosis, the
      efficiency of ozone therapy and traditional treatment in patients with diabetes
      mellitus complicated by pyonecrotic lesions of the lower extremities].
AB  - The severity of endotoxicosis was evaluated in 128 patients with type 2 diabetes
      mellitus complicated by pyonecrotic lesions of the lower extremities. There was
      evidence for a reduction in serum albumin concentration, which led to diminished
      detoxication capacities of the body. Concurrently, the effective albumin
      concentration and the binding capacity of both albumin and plasma became lower,
      which suggested higher blood toxicity. There was imbalance between the formation,
      accumulation and binding, utilization and elimination of toxic products, as
      confirmed by a rise in calculated intoxication criteria. Traditional therapy did
      not cause a significant reduction, which requires special detoxication therapy.
      Ozone therapy, an oxidative detoxication method substantially diminishes the
      severity of endogenous intoxication, as supported by an increase in the total
      concentration of albumin and its functional properties.

PMID- 18724430
TI  - [Design of an immunochip for separate detection of hepatitis C virus antibodies].
AB  - A test kit as an immunochip designed for the diagnosis of hepatic C virus (HCV)
      has a high sensitivity and specificity. Recombinant HCV antigens were separately
      immobilized on the activated slides together with internal controls. Serum test
      results were red by ScanArray Express. K-factor and corresponding value of cut
      off were calculated for each antigen and internal controls. Comparative
      evaluation of the sensitivity and specificity of the immunochip was carried out
      by commercial ELISA test kits and linear blotting analyses on 448 blood samples
      containing and free from NCV antibodies.

PMID- 18724431
TI  - [Calcium homeostasis and nitric oxide processes in children with migraine].
AB  - Eighty-one children aged 6 to 17 years who had migraine were examined by clinical
      and biochemical studies. The activity of Ca2(+)-ATPase and the levels of total
      intracellular calcium of platelets and plasma nitrites were studied in the attack
      free period. Children with migraine were fond to have elevated levels of stable
      nitric oxide metabolites (nitrites). The level of intracellular calcium was 2
      times greater than that in healthy children of the same age, which was followed
      by compensatory Ca2(+)-ATPase activation. There was a relationship of the
      parameters of calcium homeostasis and the plasma level of nitrites to the
      clinical and pathogenetic manifestations of migraine.

PMID- 18724432
TI  - [Absence of hepatitis C virus RNA in ambiguous results of mass blood screening
      for hepatitis C virus antibodies].
AB  - The purpose of the study was to elucidate whether hepatitis C virus (HCV) RNA was
      present in the blood of patients from a Moscow therapeutic-and-prophylactic
      institution with uncertain results of a study of anti-HCV that were obtained
      using the algorithm developed for mass screening. The two-stage scheme of testing
      the serum for anti-HCV, which was obligatory in accordance with the Order of the
      Ministry of Health of the Russian Federation, was supplemented by a study the
      samples having a low optical density samples and those with controversial results
      in the test systems with the expanded spectrum of detectable anti-HCV, the
      instructions of which comprises criteria for an uncertain result. Sera with
      uncertain results of anti-HCV tests were assessed by two polymerase chain
      reaction (PCR) techniques for HCV RNA. The cDNA fragments complementary to HCV
      RNA were detected in the sera obtained from two elderly persons in PCR when a
      signal was recorded in agarose gel. The other real-time PCR failed to detect RNA
      in none sera with an uncertain result as to anti-HCV.

PMID- 18724433
TI  - Inform parents of teen's STI?

PMID- 18724435
TI  - Finding the right depression medication.  STAR*D and other studies provide
      guidance, but the research continues.

PMID- 18724436
TI  - Involuntary outpatient commitment.  An update about the controversies and
      possible alternatives.

PMID- 18724437
TI  - Alzheimer's and driving ability.  Knowing when it may be time for someone to
      surrender the car keys.

PMID- 18724438
TI  - Anti-inflammatory drugs may not protect cognitive function.

PMID- 18724439
TI  - What is Munchhausen's syndrome by proxy and why is it not in the DSM-IV?

PMID- 18724441
TI  - Update on preventing mother-to-child transmission. Post-partum therapy for moms
      and infants, plus drug resistance in offspring. Press release from U.S. Centers
      for Disease Control and Prevention.

PMID- 18724440
TI  - Antiretroviral therapy roundup from CROI. Report on newer drugs in development
      and some already approved drugs.

PMID- 18724442
TI  - Death of a vaccine. CROI update on the unexpected failure of the STEP Study.

PMID- 18724443
TI  - The price of surviving HIV. Aging and complications.

PMID- 18724444
TI  - Prevention updates from CROI. Suppression of genital herpes, circumcision, and
      serosorting as prevention.

PMID- 18724445
TI  - Tesamorelin for fat accumulation. 52-week effects and safety of tesamorelin
      (growth hormone releasing factor) in HIV patients with fat accumulation.

PMID- 18724446
TI  - Co-infection at the 2008 Retrovirus Conference. Liver fibrosis, hep c treatment,
      and the role of ART.

PMID- 18724447
TI  - Clinical trial update. The Setpoint Study (Study A5217). A randomized study
      comparing immediate treatment vs. treatment as indicated in newly-infected HIV
      positive patients.

PMID- 18724448
TI  - Delivery past due: global precedent set   under Canada's Access to Medicines
      Regime.
AB  - Four years to the month after Parliament passed a law to enable the supply of
      lower-cost generic medicines to developing countries in need, the first exports
      are finally about to happen. In this article, Richard Elliott provides an
      overview of recent developments under Canada's Access to Medicines Regime (CAMR),
      and identifies key reforms needed to streamline the regime so that it can more
      easily be used to address public health problems in developing countries.

PMID- 18724449
TI  - Developing guidance for HIV prosecutions:   an example of harm reduction?
AB  - Extensive discussion of the global trend towards the prosecution of individuals
      for HIV transmission has tended to focus on arguments of principle for or against
      such prosecutions. There has been less examination of how, where prosecutions are
      taking place, the community, the voluntary sector and relevant professional
      bodies (hereinafter the "HIV sector") can mitigate ensuing harm and maximise
      fairness and understanding in the criminal justice process. In England and Wales,
      where prosecutions for reckless HIV transmission have been taking place since
      2003, the HIV sector persuaded the Crown Prosecution Service (CPS) to consult on
      the production of Legal Guidance for CPS prosecutors and caseworkers (hereinafter
      "Guidance") in this area of law, as well as an accompanying Policy Statement. In
      this article, Yusef Azad describes both the process and the outcome, and attempts
      an initial assessment of whether this intervention has benefited people living
      with HIV.

PMID- 18724450
TI  - Access to condoms in U.S. prisons.
AB  - Despite overwhelming evidence that condom use prevents the transmission of HIV,
      U.S. prison officials continue to limit the availability of condoms to
      incarcerated persons. Concern for transmission of HIV in prison and in the
      community upon prisoners'release has increased the interest of some policymakers
      in the issue. In this article, Megan McLemore addresses security concerns as well
      as human rights arguments in support of efforts to adopt a public health approach
      to harm reduction in U.S. prisons.

PMID- 18724451
TI  - Legislation imposing mandatory   minimum sentences for drug   offences passes
      second reading.
AB  - Bill C-26, An Act to amend the Controlled Drugs and Substances Act, passed second
      reading in the House of Commons on 16 April 16 2008, and was referred to the
      Standing Committee on Justice and Human Rights. The legislation has been proposed
      as a component of the National Anti-Drug Strategy.

PMID- 18724452
TI  - Manitoba legislation would authorize testing   for HIV without informed consent.
AB  - Manitoba's Health Minister has introduced legislation that would authorize the
      forced testing of people for HIV and other infections in some situations of
      possible occupational and non-occupational exposure to blood or other bodily
      fluids.

PMID- 18724453
TI  - Organ donation regulations limit   donations from gay men.
AB  - New federal regulations intended to protect the health and safety of transplant
      recipients came into force on 7 December 2007.

PMID- 18724454
TI  - Complaint filed concerning judge's conduct.
AB  - During a trial in December 2007, when it was disclosed that the complainant was
      living with HIV and hepatitis C, the presiding judge ordered the complainant to
      be masked or testify electronically from another courtroom. The Canadian HIV/AIDS
      Legal Network and the HIV& AIDS Legal Clinic of Ontario (HALCO) lodged a formal
      complaint with the Ontario Judicial Council in response to what they termed
      "shockingly discriminatory thinking and practice".

PMID- 18724455
TI  - Health Canada releases report on   supervised injection facility.
AB  - A report prepared by an expert advisory committee appointed by Health Canada has
      provided further evidence of the effectiveness of Insite, the supervised
      injection facility (SIF) located in Vancouver

PMID- 18724456
TI  - Changes to the   Immigration and Refugee   Protection Act proposed   in 2008
      Budget.

PMID- 18724457
TI  - Independent review   of prisons released.

PMID- 18724458
TI  - Legislation.  AHF: flawed global AIDS bill clears Senate committee.

PMID- 18724459
TI  - Bequest.  Microsoft philanthropist makes a record donation to HIV groups.

PMID- 18724461
TI  - Discrimination.  Alabama prisons struggle with integration of inmates with HIV.

PMID- 18724460
TI  - HIV-positive Nigerian's asylum petition remanded on appeal.

PMID- 18724462
TI  - Prisons.  Officials could be liable for HIV-positive inmate's injuries.

PMID- 18724463
TI  - Discrimination.  HIV-positive woman's discriminatory-firing claim fails.

PMID- 18724465
TI  - Native American HIV/AIDS day spotlights prevention.

PMID- 18724464
TI  - ADA.  Failure to serve summons could trip up man's injury claim.

PMID- 18724466
TI  - The invisible. A quick look at the HIV/AIDS epidemic in a group often overlooked.

PMID- 18724467
TI  - Transgender therapy and HIV. Two complicated conditions rolled into one.

PMID- 18724468
TI  - Seeking validation. Transitioning is a celebration of who you are.

PMID- 18724469
TI  - One-on-one with Alexandra Billings. The star of stage and screen talks to PA
      about the importance of love, humor, and her Chicago roots. Interview by Jeff
      Berry.

PMID- 18724470
TI  - Challenges of the young and transgender. A physician describes a population near
      and dear to his heart.

PMID- 18724471
TI  - Ginger Valdez. Glamour and grit, advocacy and outreach.

PMID- 18724472
TI  - An interview with Walter Bockting, Ph.D. A leading expert on HIV in the
      transgender community explains why there's more work to be done. Interview by
      Jeff Berry.

PMID- 18724473
TI  - Policing gender and sexuality. Transgender sex workers, HIV, and justice.

PMID- 18724474
TI  - Teo's journey. A transguy struggles with addiction and isolation, and discovers
      wellness and his identity along the way.

PMID- 18724476
TI  - Lois Bates. The essence of strength, courage, and wisdom.

PMID- 18724475
TI  - A transgender therapy primer. Basic information for hormonal treatment and drug
      interactions.

PMID- 18724477
TI  - Safer sex post-SRS: a brave new world, indeed.

PMID- 18724478
TI  - Joy Morris-Hightower. Survival and transcendence, blessed and not damned.

PMID- 18724479
TI  - Antiretroviral rounds. Is that "one pill" treatment enough?

PMID- 18724480
TI  - Protease inhibitors: emerging research explores possible link with heart disease.
      Experts say PI therapy remains essential for most.

PMID- 18724481
TI  - Adherence strategies. Stressful life events have profound impact on ART. Study
      outlines public health problem.

PMID- 18724482
TI  - Congress questions effect of abstinence-only approach. Scientists, others say
      programs fail to work.

PMID- 18724483
TI  - 'Good bacteria' may aid in slowing HIV spread.

PMID- 18724484
TI  - One STEP forward, two steps back. The quest for an HIV vaccine goes on.

PMID- 18724485
TI  - CDC: number living with HIV on steady rise. New cases stable, survivors
      increasing.

PMID- 18724486
TI  - CA's streamlined HIV testing uncovering hidden infections. Stigma becomes a non
      issue.

PMID- 18724487
TI  - Adherence strategies. Fine-dining gives patients incentive to stay on meds. Viral
      loads decreased for group.

PMID- 18724488
TI  - New CCR5 antagonist enters phase II trials. Drug would be first-line therapy.

PMID- 18724489
TI  - FDA notifications. Generic zidovudine oral solution approved.

PMID- 18724490
TI  - FDA notifications. FDA approves label change for nevirapine.

PMID- 18724491
TI  - FDA notifications. New tipranavir solution approved.

PMID- 18724492
TI  - NYC reports spate of HIV false positives with oral test. CDC: tests still play
      important role.

PMID- 18724494
TI  - While other groups decline, HIV increasing in MSM.

PMID- 18724493
TI  - Roche Labs update insert for saquinavir.

PMID- 18724495
TI  - [Purification and reactivity of foot-and-mouth disease virus non-structural
      protein 3A, 3B and 2C expressed in E. coli].
AB  - OBJECTIVE: To purify and to detect reactivity of non-structural proteins 3A, 3B
      and 2C expressed in the Escherichia coli. METHODS: FMDV NSP 3A, 3B and 2C
      containing the major B-cell antigenic sites were expressed in E. coli. We got
      renatured 2C protein by lysing of isolated inclusion body using high
      concentration of urea, and then diluted in a buffer system containing
      oxidized/reduced glutathione. Purified 3A, 3B and 2C were obtained by Ni-NTA His
      Bind Resin affinity chromatography. The reactivity of three NSPs with sera of
      different origin was measured using an indirect ELISA and Western-blot. The
      reactivity of three proteins was compared with 3ABC and 3D by detecting sera of
      clinically healthy sheep that were collected from epidemic region of Asia I FMD.
      RESULTS: Proteins 3A and 3B were solubly expressed in bacteria, and 2C was
      expressed to form inclusion body. All three products could react specifically
      with sera from FMDV infected animal by western-blot and ELISA. The high
      coincident rates were observed between 3A, 3B, 2C and 3ABC. CONCLUSION: The
      results would provide useful materials for establishment of immunoelectro
      transfer blot (EITB) diagnostic method, which could be used for differentiation
      of the FMDV infected animals from the vaccinated animals.

PMID- 18724496
TI  - Deals landscape: notable deals in the pharmaceutical industry in the second
      quarter of 2008.

PMID- 18724497
TI  - [A guideline for the use of nucleoside/tide analogues in treating chronic
      hepatitis B].

PMID- 18724498
TI  - The relevance of problem-based instruction to learning about environmental
      health.
AB  - This article examines the essence of problem-based instruction and its successful
      use in teaching classes in environmental health, The author describes experience
      gained from this style of teaching and recommends how to apply it in the academy
      to teach environmental public health courses.

PMID- 18724499
TI  - The View-Master Health Study Focus Groups.
AB  - Trichloroethylene (TCE), a common groundwater contaminant, was found at high
      levels at an Oregon work site in 1998. According to a recent report released by
      the National Research Council, "the evidence on carcinogenic risk and other
      health hazards from exposure to trichloroethylene has strengthened since 2001." A
      convenience sample of 13 former workers from the Oregon work site was recruited
      for a series of focus groups. Information obtained on plant processes, safety
      procedures, attitudes regarding medical record access, and opinions about proxy
      accuracy was subjected to qualitative content analysis. Workers recalled few
      safety policies and no training or support for control of safety. Most thought co
      workers and family members would be the best source of proxy exposure information
      and favored granting access to medical records. Job-role mobility confirmed the
      importance of using a job or task exposure matrix. Information obtained will be
      used in development of an exposure assessment interview tool.

PMID- 18724500
TI  - Role of environmental health professionals in improving the built environment.

PMID- 18724501
TI  - Public health: Seattle and King County's push for the built environment.

PMID- 18724502
TI  - Smart growth and health for the future: "our course of action" Delaware County,
      Ohio.

PMID- 18724503
TI  - Tri-County Health Department in Colorado does more than just review a development
      plan.

PMID- 18724504
TI  - Tool created to assess health impacts of development decisions in Ingham County,
      Michigan.

PMID- 18724505
TI  - Technology uses live cells to detect foodborne pathogens, toxins.

PMID- 18724506
TI  - Engaging young people in children's environmental health protection through CARE.

PMID- 18724507
TI  - Drugs in the drinking water: In fiery hearing, senators urge U.S. EPA to shift
      its paradigm.

PMID- 18724509
TI  - [Informed consent. Progress in health care relations].

PMID- 18724508
TI  - The emergence of environmental health in land use planning.

PMID- 18724510
TI  - [Scientific evidence supports the efficacy of mepentol milk in patients with
      vascular ulcer and diabetic foot].

PMID- 18724511
TI  - [Childbirth via the vagina birth canal. Breech presentation through the cervix
      uteri].
AB  - At the present time in our country, when faced with a breech presentation through
      the cervix uteri, the majority of hospitals carry out an elective Cesarean
      section. The Spanish Association of Gynecology and Obstetrics does not indicate a
      strict operating protocol for these cases. The authors carry out a transversal
      study to test a mother's and her child's state of health after having undergone
      birth through the vagina birth canal when a breech presentation through the
      cervix uteri occurred, using various parameters for their analysis. Our results
      indicate that with the mother's consent and in the situations indicated, to have
      birth via the vagina birth canal when there is a breech presentation through the
      cervix uteri can be tried.

PMID- 18724512
TI  - [Rear nasal blockage and other tricks].
AB  - From her personal perspective, the author explains diverse "tricks" and skills
      which can be put into practice when dealing with various emergency situations. In
      this article the author describes some which apply to rear nasal blockages so
      that their treatment becomes a safe, sure, easy procedure; she also describes a
      few tricks for other emergency situations medical professionals have to resolve.

PMID- 18724513
TI  - [Informed consent. Efficient communication and autonomous decision-making].
AB  - Informed consent belongs to a new way to understand doctor-patient relationships
      from a perspective permitting a principle of autonomy. Seen from this viewpoint,
      we speak of a medical relationship understood as being a mutual relationship. For
      a decision to be autonomous, it must be intentional, taken after adequately
      understanding all the pertinent information and totally free from outside
      influences. We must realize that from both theoretical and practical views
      objections exist; these include paternalism, comprehension difficulties, or
      patient refusal to exercise informed consent. Informed consent presents a reality
      and a challenge for our profession since it is much more complex than a simple
      signature on a document.

PMID- 18724514
TI  - [Cutting forceps. Classification (and II)].
AB  - The most common and also the simplest guideline to gain an efficient awareness
      about existing surgical instruments consists of, once you know their physical
      characteristics, establishing a relationship between every instrument and every
      organ or tissue, or otherwise to associate each instrument to a determined
      operating specialty, having a specified technique, etc. Through this method, a
      professional will act correctly in the majority of situations since each surgical
      specialty tends to opt for one unique model of cutting forceps in each instrument
      system both to reduce costs as to reduce the number of instruments.

PMID- 18724515
TI  - [Concordance among samples taken from a subcutaneous reservoir and a peripheral
      puncture].
AB  - Many patients who undergo phlebo-toxic treatment eventually require central vein
      access ways and of these accesses, the most common one used among oncology
      patients due to its advantages is a subcutaneous reservoir. The objective of this
      study was to verify the concordance among samples obtained from a subcutaneous
      reservoir using the rejection technique, and those obtained when using a direct
      puncture technique. This study included 22 patients who were carriers of a
      subcutaneous reservoir and who visited outpatient services during March and April
      in 2006. The study authors obtained simultaneous samples from subcutaneous
      reservoirs and from peripheral veins. These parameters were compared by means of
      an intra-class correlation coefficient. Only hematology parameters, that is
      leucocytes, hematocrits, hemoglobin and platelets, showed an adequate
      concordance.

PMID- 18724516
TI  - [Restoring treatment with continuous insulin infusion pump (BICI)].
AB  - Significant advances in the treatment of diabetes have been made over the past
      few decades, although insulin treatment is the only option available until now
      for Type I diabetes patients. Type I diabetes is generally diagnosed in youths;
      therefore, micro insulin injectors enable doctors to offer them a better life
      style, preventing future complications. Medical professionals contemplate the
      possibility to use this treatment on patients over age 60 with satisfactory
      results. Continuous insulin infusion pumps (BICI) provide physiologically
      programmable subcutaneous administration of rapid acting insulin. Due to
      technological advances, these pumps have become safer more efficient and easier
      to use which improves the glucose level in blood and enables diabetes patients to
      carry out many activities without losing metabolic control, reduces the
      incidences of hypoglycemia and improves diabetes patients' life styles.

PMID- 18724517
TI  - [Gasometric arterial extraction].
AB  - Gasometric arterial extraction comprises a simple, painful and invasive technique
      through which a nurse obtains arterial blood by a direct puncture of an artery be
      it radial, brachial or femoral, or to insert a cannula in a radial artery This
      method serves to evaluate the pulmonary gas interchange and to study alterations
      in acid-base balances. The authors' objective is to unify criteria for
      extraction, conservation and transfer of samples to laboratory. To carry out our
      study, the authors made a wide bibliographical review on the subject and arrived
      at the following conclusions: All the articles reviewed counseled medical
      personnel to follow the "SEPAR" (Spanish Association of Lung and Thoracic
      Surgery) norm, but there is no unanimous recommendation regarding the type of
      local anesthetics to use before making the puncture. Nursing personnel are those
      responsible for extracting arterial blood. The majority of authors coincide
      stating that the conservation of the sample, the time which lapses after its
      extraction and the extraction conditions affect the reliability of the results.

PMID- 18724519
TI  - [Stop the violence. Interview by Veronique Robert].

PMID- 18724520
TI  - [In some community health information centers. Interview by Jeanne Morazain].

PMID- 18724521
TI  - [High precision].

PMID- 18724522
TI  - [At the regional level].

PMID- 18724523
TI  - [Optimal preparation].

PMID- 18724524
TI  - [The wheels of communication].

PMID- 18724525
TI  - Lessons from the evolution of 401(k) retirement plans for increased consumerism
      in health care: an application of behavioral research.
AB  - Employment-based health and retirement benefit programs have followed a similar
      path of evolution. The relative decision-making roles of the employer and the
      worker have shifted from the employer to the worker, and workers are more
      responsible than perhaps they ever have been for their well being--both in terms
      of their health in general and their financial security during retirement. This
      shift has been supported, in part, by legislation--namely ERISA, the HMO Act of
      1973, the Revenue Act of 1978, and most recently, the Pension Protection Act.
      This Issue Brief does not pass judgment on this development or address who should
      bear the responsibilities of preparing workers for retirement or of rationing
      health care services. The current trend in health care design is toward increased
      "consumerism." Consumer-driven health is based on the assumption that the
      combination of greater cost sharing (by workers) and better information about the
      cost and quality of health care will engage workers to become better health care
      decision makers. It is hoped that workers will seek important, necessary, high
      quality, cost-effective care and services, and become less likely to engage
      providers and services that are unnecessary and ineffective from either a quality
      or cost perspective. As employers look ahead toward continually improved plan
      design, there may be benefits in considering the lessons learned from studying
      worker behaviors. Specifically, there is evidence about the effects of choice,
      financial incentives, and information on worker decision making. As a result of
      research in this area, many retirement plan sponsors have moved toward plan
      designs and programs that recognize the benefits of well-designed defaults,
      simplified choices, required active decision making, framing, and commitment to
      future improvements. With respect to choice, it is now known that more is not
      always better and may even be worse in some cases. Just as fewer shoppers
      actually bought a jar of jelly when it was one of 24 as opposed to one of six,
      evidence has shown that people tend to be less likely to join a company-sponsored
      retirement plan when more investment options are offered. More choice can also
      lead to lower satisfaction. It is also known that workers may not be able to
      appropriately sort through many complex alternatives and that education is not
      always as effective as employers would hope. Decision complexity often forces
      people to find a way to simplify, and one of the easiest rules of thumb is to
      pick the option with the lowest short-term cost, even when that alternative is
      more costly in the longer run. It is also known that, for good or for bad,
      choices are constructed on the fly; preferences are dynamic, and logic does not
      always apply. Financial incentives are helpful in motivating behavior, but they
      do not affect everyone's decisions. Despite significant financial incentives to
      participate in 401(k) plans, many workers choose not to. Similarly, despite many
      of the financial incentives embedded in health care plan design, it can be
      expected that these incentives will not effectively motivate and engage all
      workers. One seemingly rational approach to improve workers' decision making is
      to provide education and guidance to help them sort through complex alternatives
      and to demonstrate the value of financial incentives. Certainly, providing
      education and guidance in the form of decision support tools may be an employer's
      responsibility. However, some studies have shown that, even when "educated"
      workers have the intent to make improved decisions, they often lack follow
      through and fail to take action. In short, education and guidance may not be
      enough to foster improved health care consumerism. Some employers have begun to
      design benefit programs with a view toward overcoming behavioral tendencies that
      negatively affect workers' well-being. Newer retirement plan designs involve
      careful consideration of default choices. These defaults apply unless workers
      actively choose a different alternative. Typically, the default attempts to
      "nudge" workers toward optimal behavior. In the case of 401(k) retirement plan
      design, more employers are moving toward a default of automatic enrollment in the
      plan, with automatic investment in a diversified portfolio. Still, additional
      empirical research and experimentation may be needed to further understand the
      effects of new retirement plan design features. Future work may also precisely
      illuminate how the lessons discussed in this Issue Brief may apply to health care
      plan design that results in improved health-related behaviors. Given the
      impressive preliminary results in improving retirement planning behaviors, such
      research and experimentation are likely to be worthwhile.

PMID- 18724526
TI  - [Medical ethics and ethicotherapy II].
AB  - The care of the spiritual dimension in the framework of concept total pain
      appears to be an essential component of the care of seriously ill. In the western
      developed countries such care is provided by hospital chaplain and it is
      standardized. In the Czech Republic, pretending the care of a religious patients,
      an idea of wider approach to the spiritual care occurred, provided by spiritual
      counselor. Such opinion is advocated by a medical doctor, who deals with non
      ethical ethicotherapy, related to esoterism. Introduction of such crypto
      religious model is untrue by itself and includes several dangerous moments.

PMID- 18724527
TI  - [Metabolic syndrome and skin diseases].
AB  - Skin symptoms were originally described only in some components of the metabolic
      syndrome (e.g. in obesity, diabetes and polycystic ovary syndrome). In the last
      years several skin symptoms were described also in the metabolic syndrome. These
      relations were mostly described between psoriasis and metabolic syndrome, where
      perhaps common pathogenetic mechanisms are present. Even more important is the
      fact that physical activity, weight loss and diet treatment can have a common
      positive effect on both diseases. Also some drugs can influence both diseases
      together.

PMID- 18724528
TI  - [Conduct disorders in seven-year-old children--results of ELSPAC study. 2. Risk
      factors].
AB  - BACKGROUND: Conduct disorders related to hyperactivity and significant attention
      deficit are caused by several types of risk factors-genetic, biological,
      environmental and psychosocial. A cohort of children was followed longitudinally
      in a prospective study during the pregnancy and childhood (ELSPAC). In the age of
      7 years, marked behavioural divergences were described in 4,4% of children by
      their attending physicians. These children were also more often afflicted by
      other pathological symptoms (hyperactivity, sleep and psychomotor disorders).
      From the data collected from parents and physicians in the previous phases of
      investigation we selected possible risk factors which affect the prenatal and
      postnatal periods: prenatal exposure of children to smoking, alcohol, chemical
      substances, prenatal development complications, the level of education of
      parents, family dysfunction, alcoholism of both parents, conflicts with the
      police, mother's disturbed mental health. METHODS AND RESULTS: In the sample of
      3752 children from the city of Brno, no behavioural divergence was found in 96.5%
      of cases. The presence of one or two of the four observed divergences occurred in
      3.2% and 3 to 4 conduct disorder symptoms occurred in 0.3% children,
      significantly more often in boys. The children with conduct disorders compared to
      the children with no symptoms had significantly lower average birthweight, lower
      head circumference, their mothers had more often lower education, smoked and had
      psychological problems in childhood and as adults and the fathers had more often
      conflicts with the law. CONCLUSIONS: The ELSPAC study did not have the
      methodological possibility of studying the genetic-environmental interactions;
      nevertheless it contributes to the evidence supporting that some factors can
      negatively effect the foetal development and the unfavourable family environment
      can participate in the development of conduct disorders which can progress during
      lifetime.

PMID- 18724529
TI  - [Effect of growth factor on the phenotype of subpopulations and on the kinetics
      of CD34+ cells in the peripheral blood and in grafts of peripheral stem cells in
      patients with non-Hodgkin's lymphoma indicated for autologous peripheral blood
      stem cell transplantation].
AB  - BACKGROUND: Peripheral blood stem cells are the preferred source for
      transplantation of hematopoiesis in patients with non-Hodgkin's lymphoma.
      Application of hematopoietic growth factors is a part of the mobilization
      chemotherapy regimen. Time overlap of the highest leukocyte and CD34+ cell count
      is required for optimal graft collection. Authors analyzed the effect of two
      growth factors (leridistim and filgrastim) on the kinetics and phenotype of CD34+
      cells in patients with non-Hodgkin's lymphoma indicated for autologous peripheral
      blood stem cell transplantation. METHODS AND RESULTS: Authors analyzed phenotype
      of CD34+ cell subpopulations and their kinetics in peripheral blood and
      leukapheresis products by flow cytometry during mobilization and graft
      collection. Statistically significant differences in expression of lineage
      committed antigens between growth factors were found (CD3, CD5--T-lineage, CD56
      NK-lineage, CD20 for B-lineage, p < 0.05), as well as for lineage non-specific
      antigens (CD38, p < 0.05 and CD54, p < 0.01). The most significant divergence was
      observed between CD34+CD19+ subpopulations of leridistim and filgrastim
      stimulated blood and graft (p < 0.001). CONCLUSIONS: Expression of lineage
      committed antigens on CD34+ subpopulations between two growth factors was
      statistically different. Kinetics of CD34+ cells during mobilization regimen with
      leridistim was not superior to filgrastim concerning the quality of graft.

PMID- 18724530
TI  - [Changes in the urinary bladder caused by short-term permanent catheter
      insertion].
AB  - BACKGROUND: Short-term urinary bladder drainage using a permanent Foley catheter
      is practised frequently in hospitals. The catheter usually hurts the bladder
      mucosa and submucosa to various degrees. The aim of this study was to show
      pathological changes observed during a time period of one to 30 days of catheter
      treatment. METHODS AND RESULTS: Samples for histological testing were taken from
      the posterior wall of the bladder of deceased patients. The posterior wall
      exhibited maximal injury. Same steps were done in 10 bladders of the deceased
      patients who had not been catheterised at all. There were 41 patients in the
      tested group, of an average age 70 years (22 men and 19 women). In microscopy the
      mucosa was oedematous, hyperaemic with ectatic vessels and haemorrhages. Polyps
      were also seen, some of them haemorrhagic. Polypous cystitis was revealed in 29
      cases (70%), and various mucosal defects in 12 cases (29%). A predominance of
      fibroblasts was observed in the reactive stromal cells of the bladder wall.
      CONCLUSIONS: Polypous cystitis develops already in the first days after permanent
      catheter insertion. The recent polyps present an inflammation caused by
      mechanical injury. The number of reactive stromal cells increases only partly on
      the dependence on the duration of permanent catheter treatment. These are
      abundant in the polyps and where mucosal defects occur. The presence of these
      cells may also be influenced by spontaneous chronic inflammation or nodular
      prostate hyperplasia in men. The occurrence of eosinophilic leucocytes was not
      observed until 3 days after catheter insertion. We cannot see any relation
      between the reactive stroma cells and mastocytes or with eosinophils.

PMID- 18724531
TI  - [Formation of the urinary stones in alkaptonuria patients].
AB  - Alkaptonuria is an autosomal recessive disease with late complications (arthritis
      and ochronosis). Excretion of alkapton (homogentisic acid) in the urine is due to
      congenital lack of the enzyme homogentisate 1,2-dioxygenase, which mediates the
      essential step in the catabolism of phenylalanine and tyrosine. Urine excretion
      of homogentisic acid is very high, urine turns dark if allowed to stand or is
      alkalinized (a result of formation of polymerization products of alkapton). The
      presence of alkapton in urine has high lithogenic effect. We report 71 years old
      man suffering from alkaptonuria with present severe late complications. In this
      man black coloured urinary calculus was extracted from the urethra. This calculus
      was formed of organic amorphous part and crystallized part analyzed by X-ray
      diffraction and infrared spectroscopy identifying weddelite and whitlockite
      (1:1), and trace amounts of carbonate apatite.

PMID- 18724532
TI  - [Hypokalaemia in a suicide attempt of an adolescent girl].
AB  - In acute theophylline poisoning hypokalaemia, hyperglycaemia, and other
      electrolyte disturbances may occur. These abnormalities have been attributed to
      catecholamine excess with intracellular movement of potassium and catecholamine
      stimulated gluconeogenesis. Herein we describe a female teenager, who developed
      metabolic disturbances with significant toxic response to oral theophylline
      overdose in a suicide attempt. Severe hypokalaemia (1.8 mmol/L) was among the
      leading pathological findings, at peak theophylline concentration (68 mg/L).
      There was high plasma glucose (10.2 mmol/L). Creatinine-kinase was evidently
      abnormal (8.60 microkat/L) several hours post poisoning, while serum myoglobin
      was markedly elevated (74.8 microg/L) despite the decrease in the drug level.
      Ventricular arrhythmia with marked extra systoles has been confirmed on
      electrocardiograph. Finally, the patient recovered through intensive care
      management with theophylline level (21.1 mg/L) falling close to reference range
      after 48 hours, but relative hypokalaemia persisted despite potassium
      supplementations even after the drug level fall below detection limit. In
      conclusion, timely gastrointestinal decontamination, determination of serum drug
      levels in intervals, electrocardiography evaluation followed by treatment of
      arrhythmias, supportive care including balancing of metabolic disturbances,
      follow-up assessment of serum electrolytes, in particular potassium and
      creatinine-kinase parallel with myoglobin level assessment even after significant
      decrease in theophylline level are very important measures.

PMID- 18724533
TI  - [Sir Alexander Fleming].

PMID- 18724534
TI  - Weekly docetaxel regimens and radiation pneumonitis.

PMID- 18724535
TI  - Esophageal stenting for the palliation of malignant dysphagia.
AB  - Self-expanding metal stents (SEMS) are currently the standard for palliation of
      malignant dysphagia. Innovations in stent technology, including the advent of
      retrievable stents and the development of self-expanding plastic stents (SEPS),
      show promise to increase the possible applications for esophageal stents. This
      article reviews the indications and usage of both SEMS and SEPS in patients with
      malignant dysphagia as well as the potential complications of their use.

PMID- 18724536
TI  - Moving beyond single-modality management of malignant dysphagia.

PMID- 18724537
TI  - Balancing the benefits and risks of esophageal stenting in the palliation of
      malignant dysphagia.

PMID- 18724538
TI  - Visual analogue scales and assessment of quality of life in cancer.
AB  - Assessment of quality of life (QOL) in cancer clinical trials is important when
      comparing treatments, especially when prolonged survival is not expected. QOL
      scores may reflect physical or psychosocial functioning or distress. The choice
      of QOL instrument depends upon the definition, research hypothesis, cancer
      population, depth and sensitivity of information required, and frequency of
      measurement. A visual analogue scale (VAS) is commonly used to rate various
      subjective experiences. Potential advantages of these scales include their wide
      score range and high sensitivity; disadvantages include lower completion rates
      than other rating scales. Single-item VASs are validated for cancer QOL,
      reliable, and responsive to change. These scales may best represent an
      individual's global QOL without the constraints of predetermined domains. Single
      items are useful for frequent measurements in palliative or advanced populations
      and when information about domains is less important. Multi-item VAS QOL
      instruments vary in length and domains; they are useful in clinical trials
      enrolling patients with good performance status, but some are long and disease
      specific.

PMID- 18724539
TI  - The prognostic significance of patient-reported outcomes in pancreatic cancer
      cachexia.
AB  - Data from a clinical study of 86 pancreatic cancer patients with involuntary,
      significant weight loss (cachexia) were used to explore the relationship between
      patient-reported outcomes (PROs) and survival. In all, 28 pancreatic cancer
      patients with cachexia were given gemcitabine (Gemzar) plus 3 mg/kg of infliximab
      (Remicade), 28 were given gemcitabine plus 5 mg/kg of infliximab, and 30 were
      given gemcitabine plus placebo in a double-blinded, phase II, multicenter trial.
      PRO endpoints included scores from the Functional Assessment of Chronic Illness
      Therapy-Fatigue (FACIT-F), Functional Assessment of Anorexia/ Cachexia Therapy
      (FAACT), Brief Pain Inventory (BPI), and the Short-Form 36 general health survey
      (SF-36). Population mean scores at baseline indicated fatigue problems (FACIT-F),
      nutritional health issues (FAACT), and mild-to-moderate pain (BPI "worst pain"
      score). Baseline normalized SF-36 values for physical functioning, vitality, and
      mental health indicated substantial impairment. Baseline fatigue and physical
      functioning scores predicted survival as well as, or better than, baseline
      Karnofsky Performance Status or hemoglobin level. A cut-point in the FACIT-F
      score (median < or = 30) strongly predicted mortality; patients with greater
      fatigue had a lower median overall survival than did those with less fatigue.
      These findings supported several features of an a priori clinical-benefit model.
      Patient-reported fatigue provided powerful prognostic information; tracking of
      this symptom may be useful for treatment planning and medical monitoring of
      advanced-stage pancreatic cancer patients with cachexia. These results must be
      confirmed by larger trials.

PMID- 18724541
TI  - [The influence of guidelines of asthma management in adults in reference to
      family physicians knowledge in the field of treatment].
AB  - AIM: Assessment of the influence of the guidelines on asthma for family
      physicians in reference to their knowledge in the field of patient's treatment.
      MATERIAL AND METHODS: The assessed group consisted of 111 physicians before
      training in family medicine and guideline implemention of asthma for family
      physicians and four years later. RESULTS: The knowledge of the physicians
      accessment in the first part of the examination in the field of patient's
      treatment was low (compatibility with the guidelines was 42% in the part "General
      principles of treatment" and 65% in "Pharmacotherapy"). In the second part of the
      study, there was a statistically significant improvement (p<0.05) of the level of
      knowledge in both fields (compatibility with the guidelines was 55% in "General
      principles of treatment" and 73% in "Pharmacotherapy"). The average improvement
      for the whole Questionnaire was 12.3% (13.3% for "General principles of
      treatment" and 8.4% for "Pharmacotherapy"). CONCLUSION: Guideline Implementing
      for family physicians in the management of bronchial asthma had a significant
      influence on the improvement of knowledge about patients treatment. Provided that
      assessment of knowledge concerning treatment of patients with asthma in our study
      was declared better than real management, there is a need for modification of
      continuous medical education in order to change the behaviour of physicians.

PMID- 18724540
TI  - [Type I and II collagens and mast cells expression in the skin lesions from the
      patients with localized scleroderma].
AB  - Morphea en plaques (MP) and atrophoderma Pasini-Pierini (APP) are by most
      researchers regarded as specific types of localized scleroderma (LS), but their
      clinical picture is completely different. Fibrosing process is very complicated,
      and is connected with presence of collagen (I and III type) and extracellulare
      matrix deposits in the dermis. Probably mast cells also play an important role in
      this process. The aim of the study is estimation of the expression of type I and
      III collagens and number of mast cells in lesions from patients with APP and MP.
      36 patients were enrolled to the study. Immunohistochemical tests were performed
      to observe presence of type I and III collagens and presence of mast cells in the
      dermis. We observed that patients with APP showed lower expression of the I and
      III type collagens in the dermis than patients with MP. Expression of I type
      collagen decreases with time only among patients with MP. There was no similar
      relation for type III collagen. High and very high expression of type I and III
      collagen was observed more frequently in the active phase of the disease in
      patients with MP. Number of mast cells was higher in patients with APP than in
      MP. The number of the mast cells increases with time of disease in patients with
      MP, and there is correlation between high number of mast cells and low expression
      of the I and III collagens in the patients with MP.

PMID- 18724542
TI  - [An attempt to precise indications for treatment with systemic cryotherapy of
      patients with rheumatoid arthritis].
AB  - The prospective studies included 178 patients (43 men and 135 women) aged 30 to
      68 years, treated because of rheumatoid arthritis (R.A.). All of them were
      subjected to systemic cryotherapy, considerin the total antioxidant states in the
      serum registered before and after the cryotherapic treatment. Fluctuations of
      serum antioxidants were referred to selected clinical factors such as: sex, age,
      duration and progression of the disease. It was confirmed that among patients
      with R.A., the most beneficial clinical effects obtained through systemic
      cryotherapy may be expected in women aged up to 49 years, in whom the disease
      lasted no longer than 3 years and is in the Ist of IInd period (phase).

PMID- 18724543
TI  - [Cardiopulmonary capacity and hemodynamic changes in adults with atrial septal
      defect].
AB  - Little is known about the relation between echocardiographic parameters and
      cardiopulmonary capacity in patients with atrial septal defect (ASD). The study
      aimed to assess the value of right atrial, right ventricle and left ventricle
      dimensions and function in predicting cardiopulmonary capacity in adults with
      ASD. 52 consecutive adult patients with hemodynamic significant ASD (mean age
      38.6+/-15, range: 18-68 years; mean Qp/Qs: 2.7+/-0.7, range: 1.5-4.3) were
      enrolled into the study. The right ventricle indices were defined as follows: end
      diastolic and end-systolic area, ejection fraction (area-length method) and right
      ventricle systolic pressure (RVSP). The following right atrial parameters were
      taken into consideration: end-diastolic and end-systolic right atrial area. Left
      ventricular systolic and diastolic diameters and LV ejection fraction were
      measured as well. All patients underwent the cardiopulmonary exercise test (CPX)
      with estimation of peak oxygen uptake -VO2, anaerobic threshold -AT and VE/VCO2.
      The mean VO2 was 23.4+/-18.4 ml/kg/min (63+/-18.4% of the predicted value). The
      dimensions and ejection fraction of left ventricle did not correlate
      significantly with any CPX parameter. Echocardiographic parameters of both right
      atrial and right ventricle function were related to peak oxygen uptake in adults
      with ASD. The strongest correlation between VO2peak and RVSP was found (r=-0.7;
      p<0.001). Echocardiography seems to be efficient in predicting cardiopulmonary
      capacity in ASD patients.

PMID- 18724544
TI  - [Aggravating factors of rosacea].
AB  - Rosacea is a chronic, inflammatory skin disease which is mainly localized in the
      central region of the face. Papules and pustules appear on the erythematic
      ground. Rosacea is common in population. Four subtypes of rosacea
      (erythematoteleangiectatic rosacea, ETR; papulo - pustular rosacea, PPR; ocular
      rosacea and phymatous rosacea) are classified (according to current
      classification) and one variant rosacea (granulomatous rosacea, GR). It is
      considered that an attempt to determine of triggering factors of rosacea should
      be the first step to treatment. Then it should be tried to eliminate contact with
      them. The aim of this study was an analysis of triggering factors of rosacea. 43
      women and 26 men treated in the Dermatology Outpatient's Clinic of Jagiellonian
      University School of Medicine in Cracow were enrolled in the study. All patients
      were asked which factors trigger skin changes according to them. Patients
      mentioned most often: stress (58 percent), sun exposure (56.5 per. cent), alcohol
      (33.3 percent), exercise (29 percent), drinking coffee (21.7 percent) and hot
      meals (20.3 percent). They regarded the sun as the most strongly aggravating
      factor of rosacea (29.2 percent). It seems, that elimination and reduction of
      contact with aggravating factors is still an undervalued aspect of rosacea's
      treatment. Patients' motivation for use of prevention seems to be also very
      important. Knowledge about aggravating factors of rosacea, coming directly from
      patients' observations, may help in more effective treatment.

PMID- 18724545
TI  - [Effect of a low-energy diet on body weight and dietary intake in women after one
      year treatment].
AB  - Low-energy diet is highly recommended for obesity treatment. However, after
      success at the beginning some in some patients weight gain occurs. This study was
      aimed to evaluate changes in body weight and dietary intake in overweight and
      obese women during 1 year of a balanced low-energy diet. The study group
      comprised 70 women, aged 47.3, BMI 37.5 kg/m2. The balanced 1000 kcal diet was
      recommended. Body weight measurement, body composition assessment by BIA and
      dietary assessment were performed at entry and every 2 months of the study. Women
      were divided in 2 groups: I--women with body weight reduction achieved after 6
      and 12 months of treatment (n=38), II--women who lost weight in first 6 months
      and gained weight in the next 6 months (n=32). After 1 year treatment averaged
      body weight reduction in women was 11.9+/-8.6%. In women from group I body weight
      decrement was 16.4+/-11.2 kg (15+/-9%), and in women from group II 7.5+/-7.7 kg,
      (8.1+/-6.7%), respectively. Body fat mass decrease in group I after 6 and 12
      months was 7.8+/-6.0 kg and 11.1+/-7.9 kg, in group II 6.4+/-5.3 kg and 5.2+/-5.5
      kg, respectively. Women from group II consume more energy, carbohydrates and
      sucrose in months 6-12 than in first 6 months and more than women in group I
      (p<0.05). During 1 year in group I calcium intake and Ca/protein index increased
      statistically significant, and in group II decreased. Changes in energy and
      nutrients intake do not correlate with achieved results. After 1 year of a low
      energy diet statistically significant reduction of body weight and body fat mass
      were stated. Increase in energy, carbohydrates, sucrose intake and decrease in
      calcium intake could contribute to weight gain in studied women.

PMID- 18724546
TI  - [Possible application of lectins in diagnostics and therapy. Part I. Diagnostic
      application].
AB  - Lectins are proteins or glyco-proteins binding selectively and without the
      involvement of enzymes specific for carbohydrate ligands. Lectins are present in
      organisms on different levels of evolutionary development and play very important
      roles in life processes of these organisms. Lectins' functioning mechanism is
      based on the reaction of glycolysation. In vertebrates, functions of lectins are
      connected with cell recognition, proliferation control, adhesion, cell
      differentiation, mechanisms of organ creation, and defense mechanisms. Due to
      their ability to bind reversibly with specific carbohydrate structures, Lectins
      have commonly been used as a perfect molecular tool in various disciplines of
      biology and medicine. With the use of modern methods of lectin affinity
      chromatography (LAC) and various histochemistry methods, lectins provide
      practical application during observation of changes occurring in the cell
      membrane in different stages of physiological and pathological development of
      human or animal organisms. What is particularly important is lectins'
      contribution to studies on the isolation and structure of glycoconjugates in
      clinical pathology (including processes of tumor transformation). Serology was
      the first discipline of medicine relying on the specific activity of lectins. It
      had been based on the discoveries (by Rekonen in 1948 and Nowell in 1960) that
      proved that some lectins are able to bind with human and animal blood group
      antigens. Another discovery (by Nowell in 1960s) of mitogenic effect of PHA on
      human lymphocytes made lectins helpful and commonly used in the diagnosis of
      genetic conditions in several diseases. Proving that lectins bind differently
      with glycoconjugates of normal and tumor cells and are able to detect subtle
      neoplastic changes was a clue that lectins can be precious and useful in cancer
      treatment and diagnostics. For many years lectins inducing apoptosis, with immuno
      modulatory or antiproliferative activity and toxic lectins belonging to II-RIP
      class (Ribosome Inactivating Proteins like viscumin, ricin) have been intensively
      examined in therapy of various diseases, esp. in cancer. Currently the use of
      lectins in drug targeting is being examined (lectins as drug-carriers, the
      preparation of bioadhesive "Second Generation" drug-delivery systems). Paper
      presents below is an attempt at collecting the latest information on diagnostic
      and therapeutic application possibilities of lectins.

PMID- 18724547
TI  - [Physiological maternal changes during pregnancy and their consequence in GP
      practice].
AB  - Physiological maternal changes, as well as signs and symptoms during pregnancy
      were presented. Changes in cardiopulmonary, urinary, digestive tract, metabolic
      and endocrinal changes in the light of practical application in G-P practice were
      presented.

PMID- 18724548
TI  - [Sinusoidal obstruction disease (SOS), previous hepatic venoocclusive disease
      (VOD)--still serious complication after hematopoietic stem cell transplantation].
AB  - Hepatic venocclusive disease (VOD) lastly named sinusoidal obstruction syndrome
      (SOS) is a serious toxicity associated with high dose therapy used to prepare
      patients for stem cell transplantation. A sizable proportion of patients who
      develop VOD/SOS die. It is clear that injury to endothelial cells and hepatocytes
      in zone 3 of the liver acinus is the initial event in the pathogenesis of
      VOD/SOS. Although clinical presentation and diagnostic criteria are well known,
      the cause of VOD/SOS, its prevention and treatment remain still unclear.
      Currently treatment of VOD/SOS has largely consisted of supportive measures
      designed to maintain intravascular volume and decrease interstitial edema. Other
      treatments used with various measures of success have included substitution of
      antitrombine and glutamine or aggressive fibrinolitic and antithrombotic therapy.
      Despite these treatments, the outcome remains fairly dismal.

PMID- 18724549
TI  - [Rare pancreatic endocrine tumors].
AB  - Functional pancreatic endocrine tumors other than gastrinoma and insulinoma are
      quite rare. Some of these tumors may be part of multiple endocrine neoplasia type
      one (MEN-1) syndrome or phakomatoses. Depending on their cell type, functional
      pancreatic endocrine tumors may cause distinct clinical endocrine syndromes, such
      as the 'glucagonoma syndrome', Verner-Morrison syndrome and the 'somatostatinoma
      syndrome'. The significant progress made in recent years, especially in the field
      of imaging procedures, has brought about great improvement in the identification
      and differentiation of these neoplasms. Currently, the only curative treatment
      for islet cell tumors is complete surgical resection. The medical treatment of
      endocrine pancreatic tumours consists of somatostatin analogues, chemotherapy,
      and interferon-alpha. The purpose of this manuscript is to provide an overview of
      the contemporary etiopathogenesis, diagnosis and treatment of rare pancreatic
      endocrine tumors.

PMID- 18724550
TI  - [Venous thrombosis and thrombosinusitis of the brain--descriptions of two cases].
AB  - In two patients with headache and seeing disorders on the basis of angio-MR
      examination venous thrombosis and thrombosinusitis of the brain and of internal
      jugular was diagnosed. The cases presented pay direct attention at the
      disproportion between the scope of the thrombotic process and a low-symptom and
      nonspecific clinical picture. In the first case after applying standard heparin,
      we obtained a nearly complete recanalisation of the vessels; in the second
      patient after application of low-molecular-weight heparin recanalisation didn't
      occur. So far no standards of therapeutic proceedings have been established in
      venous thrombosis and thrombo-sinusitis of the brain. It is still a very serious
      diagnostic and therapautic problem.

PMID- 18724551
TI  - Against the odds.
AB  - The history of the development of humidifiers as a necessary accompaniment to
      mechanical ventilation is a fascinating one. In New Zealand in the 1960s, Fisher
      and Paykel, an established importer of a variety of household appliances,
      launched into the design and manufacture of humidifiers following the
      requirements envisaged at that time, for optimal use in the intensive care
      setting. This was a completely new venture for the company and led to the
      establishment of a separate Fisher and Paykel Health Care company for medical
      equipment manufacture, which has continued successfully to the present day.

PMID- 18724552
TI  - Dr Corlette and the first textbook of regional anaesthesia in Australia.
AB  - The first Australian textbook on regional anaesthesia was published in 1948 by a
      surgeon, Dr Cyril Corlette. He was 80 years old at the time but had lectured,
      published and strongly promoted regional anaesthesia his whole career. He was a
      renowned teacher and a Founder of the Royal Australasian College of Surgeons. He
      also published controversial work on heat loss under anaesthesia and anaesthetic
      mortality. This textbook, "A Surgeon's Guide to Local Anaesthesia", subtitled "A
      Manual of Shockless Surgery", helped to promote the concept of regional
      anaesthesia in Australia.

PMID- 18724553
TI  - History of analgesia and regional anaesthesia through philately.
AB  - Medical philately is the study of postage stamps commemorating events and
      pioneers in the field of medicine. In 1929, Dr Fielding H. Garrison, doyen of
      medical history, remarked that stamps were a great resource for the medical
      fraternity, something he hoped that physicians would soon recognise. His
      prediction has hardly come to fruition in the years since then, with medical
      philatelic articles rarely seen in the medical press. The history of pain
      medicine is unique, diverse and extremely interesting, with many chemists,
      physicists, philosophers, contributing in their own way over centuries to pave
      the path to present day pain medicine.

PMID- 18724554
TI  - Mismatched connections.
AB  - Historically, anaesthetic equipment manufacturers used a number of differently
      sized connectors in anaesthetic breathing systems. This gave rise to the
      potentially dangerous possibility of mismatched taper connections and a failure
      to create a gas-tight breathing system capable of ventilating a patient. The
      British Standard 3849 of 1965 attempted to correct this problem but
      manufacturers' designs, in some cases, still caused problems. The problem was
      aggravated by a move to adopt a slightly different International Standards
      Organisation design. By the time that universally-interchangeable connectors were
      widespread twenty years later disposable breathing systems had replaced the old,
      heavy metal connectors.

PMID- 18724555
TI  - The origins of the sniffing position and the Three Axes Alignment Theory for
      direct laryngoscopy.
AB  - The Three Axes Alignment Theory and the sniffing position for direct laryngoscopy
      are the anatomical basis for direct laryngoscopy. This position has been one of
      the hallmarks of airway management and yet its development is based on a small
      number of descriptive texts published between 1852 and 1944. This paper explores
      the origins of direct laryngoscopy and how the sniffing position came to be
      described. The seemingly incongruent techniques of the rigid bronchoscopist and
      direct laryngoscopist are discussed from an historical perspective.

PMID- 18724556
TI  - The Bonnievale disaster of 1907.
AB  - In a museum at the Coolgardie Railway Station, Western Australia, a most unusual
      piece of equipment is exhibited. On display is diving gear which was used in a
      dramatic rescue attempt from a flooded mine just over a hundred years ago. The
      rescue of the trapped miner rates as an epic in Australian mining history,
      alongside that of two miners in Beaconsfield, Tasmania, in 2006.

PMID- 18724557
TI  - From collection to museum: the development of the Geoffrey Kaye Museum of
      Anaesthetic History.
AB  - Located at the Australian and New Zealand College of Anaesthetists (ANZCA)
      headquarters in Melbourne, Victoria, this internationally significant collection
      was founded in 1935 by renowned Australian anaesthetist Dr Geoffrey Kaye (1903 to
      1986). Although it has always been referred to as a museum, it lacked the
      necessary management structure and infrastructure to meet museum standards. In
      March 2003, the first full-time professionally trained Museum Curator Ms
      Elizabeth Triarico, was employed by ANZCA to work with the Honorary Curator Dr
      Rod Westhorpe, and the Honorary Assistant Curator; Dr Christine Ball, to build on
      past achievements and to develop the collection into an accessible and relevant
      modern museum. Ms Triarico has extensive museum management experience with
      emphasis on management of major projects, collection management, strategic
      planning, marketing, interpretation and exhibition development. This paper
      outlines the management issues and innovative strategies involved in developing
      this important collection into a professionally managed museum based on best
      practice standards. It illustrates the benefits of introducing a clear vision and
      an agreed longterm management plan based on Museums Australia (Victoria) Museum
      Accreditation Program guidelines.

PMID- 18724558
TI  - Occupational health and safety in medical museums.
AB  - Medical museum collections provide challenges in occupational health and safety
      that do not become apparent in many other collections. During the recent
      development of the Geoffrey Kaye Museum of the Australian and New Zealand College
      of Anaesthetists, these challenges were addressed, following the guidelines of
      the Occupational Health and Safety Regulations of the State of Victoria. This
      paper details these regulations and their necessary application in this
      specialist museum.

PMID- 18724560
TI  - Building on a legacy. Team revitalizes classic hospital design.

PMID- 18724559
TI  - The Geoffrey Kaye Museum of Anaesthetic History: creating a meaningful display.
AB  - There have been several displays created at the Geoffrey Kaye museum over the
      last 20 years. The current display is the culmination of a new professional
      approach to the management of the collection. A timeline has been created to
      enhance conducted tours and to allow self-guided tours. The creation of this
      display brought new challenges to those responsible for the collection but has
      resulted in a contemporary and exciting display that has been appreciated by many
      visitors.

PMID- 18724562
TI  - Floor show. Selecting the right product for the application.

PMID- 18724561
TI  - Ambulatory advice. Seven steps to a successful hospital outpatient facility.

PMID- 18724563
TI  - Learning exchange. NFPA conference provides education for health care
      professionals.

PMID- 18724564
TI  - Testing the system. Managing hospital waste during a pandemic event.

PMID- 18724565
TI  - Recent advances in autism spectrum disorders.
AB  - OBJECTIVE: This review article provides an overview of the most recent
      developments in the literature regarding autism spectrum disorders including
      epidemiology, etiology, assessment, and management/treatment. METHOD: A review of
      the recent literature was conducted using Medline and the search term "Autism
      Spectrum Disorders." RESULTS: Autism Spectrum Disorders are more common than
      previously believed (1 in 166), and etiology appears to be multifaceted including
      both heritable and non-heritable factors. State of the art treatment includes
      comprehensive medical monitoring as well as behavioral intervention. CONCLUSIONS:
      Current and anticipated federal funding, policy changes, and large scale research
      projects provide promise for increasing knowledge about Autism Spectrum
      Disorders.

PMID- 18724566
TI  - The reliability and validity of the Chinese version of the Dysfunctional
      Attitudes Scale Form A (DAS-A) in a community sample.
AB  - OBJECTIVE: This study investigated the reliability and validity of the DAS-A in a
      sample of 308 Chinese adults in Hong Kong. METHOD: The reliability of the DAS-A
      and its relevant sub-scales was measured using internal consistency (Cronbach's
      alpha) and Guttman split-half reliability. Principal components analysis was
      performed to assess construct validity. Discriminant validity of the DAS-A was
      performed by examining whether the DAS-A could discriminate between the depressed
      and the non-depressed subjects in this study. RESULTS: The split-half reliability
      of the DAS-A was found to be r = 0.87; Cronbach's alpha was 0.945; and item-total
      correlations ranged between 0.36 and 0.75. Factor analysis revealed three factors
      that were similar to those that were found in other studies: Performance
      Evaluation, Need for Approval, and Anaclitic Self-Esteem. Discriminant validity
      suggested that the DAS-A discriminated successfully between the non-depressed and
      the depressed groups. Nevertheless, some differences were noticed in the relative
      strength of the factors and in the distribution of the scale items into the three
      factors. CONCLUSION: It was hoped that with this type of cross-cultural
      information, the universality of the constructs of the DAS-A could be reliably
      demonstrated.

PMID- 18724567
TI  - Comfort level of pediatricians and family medicine physicians diagnosing and
      treating child and adolescent psychiatric disorders.
AB  - CONTEXT: Twelve to twenty-one percent of children and adolescents have
      psychiatric disorders with at least mild functional impairment. Pediatricians and
      family medicine physicians prescribe 85% of psychotropic medications taken by
      children. However, little is known about the comfort level of these physicians
      with the diagnosis and treatment of psychiatric disorders in children. OBJECTIVE:
      To determine the comfort level of physicians in diagnosing and treating
      psychiatric disorders in children. METHOD: An anonymous survey was sent to
      pediatricians and family medicine physicians in upstate New York. Of 483 surveys,
      200 surveys were returned. OUTCOME MEASURES: To compare differences between
      pediatricians and family medicine physicians in comfort in diagnosing and
      prescribing medications for psychiatric disorders. RESULTS: After controlling for
      age, race, and years since residency, pediatricians were more comfortable in
      diagnosing (O.R. = 3.05, C.I. = 1.40-6.63) and prescribing stimulants for (O.R. =
      4.16, C.I. = 1.96-8.84) Attention Deficit Disorder. Family medicine physicians
      were more comfortable in diagnosing (O.R. = .28, C.I. = .14-.57) and prescribing
      medication for (O.R. = .44, C.I. = .22-.87) anxiety and depression. Despite the
      differences in comfort, there were no differences in the percentage of each group
      prescribing the different medications. Of those who were comfortable in making
      the diagnoses, 13%-64% were not comfortable in prescribing medications, although
      they did prescribe. CONCLUSIONS: Pediatricians and family medicine physicians who
      prescribe the majority of psychotropic medications for children report
      disconcerting degrees of discomfort with the diagnosis and treatment of
      children's psychiatric disorders. The authors discuss the multiple factors that
      may impact primary care physician's comfort in diagnosing and treating children
      and adolescents with psychiatric disorders.

PMID- 18724569
TI  - Pediatric case study and review: is it a conversion disorder?
AB  - OBJECTIVE: It is common in health care settings for adolescent patients to report
      physical symptoms that are unexplained by physical disease or pathophysiologic
      processes. The diagnosis of conversion disorder is difficult to make as many of
      these patients present to primary care with complex, difficult-to-understand
      medical symptoms. Patients can present with a medical dilemma and a symptom model
      consistent with a conversion disorder, but there is a danger of misdiagnosis
      without a thorough medical work up. METHOD: This case report describes a patient
      where the misdiagnosis of conversion disorder could have had devastating long
      lasting neurologic sequelae. It appeared as if an unconscious conflict was being
      expressed through physical symptoms as she had ongoing family stressors prior to
      the onset of mysterious symptoms. CONCLUSIONS: The patient was found to have a
      spinal cord arteriovenous malformation. This condition is relatively uncommon in
      the pediatric age group, and early diagnosis is rarely made.

PMID- 18724568
TI  - Comorbidity of depression with chronic diseases: a population-based study in
      Aleppo, Syria.
AB  - OBJECTIVE: To assess the comorbidity and correlates of depression in chronic
      diseases in the community in Aleppo, Syria. This has never been previously
      investigated in an Arab country. METHOD: We conducted a cross-sectional,
      population-based study in Aleppo on adults aged 18-65 (N = 2038). We collected
      data utilizing a structured interview questionnaire. Socio-demographics, general
      health information, and self-report of physician-diagnosed depression and chronic
      diseases active in the past year were obtained. We used logistic regression to
      estimate the odds of depression in chronic diseases and socio-demographic
      correlates of depression comorbid with chronic diseases. RESULTS: Mean age (SD)
      was 35.3 (12.1) years, 55% were female. In women, predictors of depression were
      heart disease (OR = 3.95, 95% CI: 1.50-10.40), hypertension (OR = 2.92, 95% CI:
      1.53-5.55), and kidney disease (OR = 2.96, 95% CI: 1.64-5.32). Depression
      comorbidity with any chronic disease decreased in higher socio-economic status
      (middle vs. low: OR = 0.28, 95% CI: 0.12-0.65; high vs. low: OR = 0.20, 95% CI:
      0.05-0.81). In men, predictors of depression were rheumatism (OR = 7.10, 95% CI:
      2.58-19.60) and respiratory disease (OR = 3.77, 95% CI: 1.23-11.60). Depression
      comorbidity decreased in residence in formal zones (OR = 0.22, 95% CI: 0.06
      0.80). CONCLUSION: Depression is associated with many chronic diseases in the
      community in Aleppo, a finding consistent with reports from other cultures.
      Potential gender-related risk factors were identified. Findings inform public
      mental health planning and support the delivery of depression treatment in
      primary care settings.

PMID- 18724570
TI  - Piracetam in severe breath holding spells.
AB  - BACKGROUND: Breath holding spells (BHS) are apparently frightening events
      occurring in otherwise healthy children. Generally, no medical treatment is
      recommended and parental reassurance is believed to be enough, however, severe
      BHS can be very stressful for the parents and a pharmacological agent may be
      desired in some of these children. OBJECTIVE: In this prospective study aim was
      to determine the usefulness of piracetam as prophylactic treatment for severe
      BHS. METHODS: Children were recruited from Neurology Clinic in Children's
      Hospital, Islamabad between January 2002 to December 2004. Diagnosis of BHS was
      based on characteristic history and normal physical examination. Piracetam was
      prescribed to those children who were diagnosed as severe BHS in a dose ranging
      from 50-100 mg/kg/day. Iron supplements were added if hemoglobin was less than 10
      gm%. Patients were seen at 2-4 weeks interval and follow-up was continued until 3
      months after the cessation of drug therapy. RESULTS: Fifty-two children were
      enrolled in the study, 34 boys and 18 girls. Ages ranged from 4 weeks to 5 years
      with mean age of 17 months. In 81% of children, spells disappeared completely and
      in 9% frequency was reduced to less than one per month and of much lesser
      intensity. Prophylaxis was given for 3-6 months (mean 5) duration. CONCLUSIONS:
      Piracetam is an effective prophylactic treatment for severe BHS.

PMID- 18724572
TI  - The prevalence of borderline personality among buprenorphine patients.
AB  - OBJECTIVE: In this study, we examined the prevalence of borderline personality
      disorder (BPD) in a sample of patients seeking outpatient treatment with
      buprenorphine for opioid addiction. METHOD: To assess for BPD, we used three self
      report surveys in a consecutive study sample. RESULTS: Of the 111 participants
      who completed all three measures of BPD, 49 (44.1%) exceeded the cut-off score
      indicative of BPD. CONCLUSIONS: Among individuals who are addicted to opioids and
      seeking treatment with buprenorphine, the prevalence of BPD, as mutually
      confirmed by three self-report measures, is quite high.

PMID- 18724571
TI  - Management of depression in ambulatory care for patients with medical co
      morbidities: a study from a national Electronic Health Record (EHR) network.
AB  - OBJECTIVE: Since co-morbid depression can complicate medical conditions such as
      cardiovascular disease and cancer, physicians may treat depression more
      aggressively in patients with these conditions. This study compared
      antidepressant medication use in persons with and without medical co-morbidities.
      METHODS: This cross-sectional study was conducted in a national network of
      outpatient electronic medical record users. Participants included active adult
      patients with an active diagnosis of depression as of 11/30/05 (the "prevalent"
      population, 185,029 patients) or a new episode of depression during the one-year
      period 12/1/03-11/30/04 (the "incident" population, 29,768 patients). For each
      population, four co-morbid conditions were defined--diabetes, coronary heart
      disease (CHD), stroke, and cancer. Prescription of antidepressant medication was
      compared for persons with and without each medical condition. RESULTS: The most
      common medical condition was diabetes, with cancer being the least common (7.6%
      and 2.4% of the prevalent population). Overall, 69.6% of the prevalent population
      and 76.1% of the incident population were treated with antidepressant
      medications. For the prevalent population, treatment was significantly more
      likely for patients with diabetes (OR 1.07, 95% CI 1.03-1.11) but significantly
      less likely for patients with CHD (OR 0.94 95% CI 0.90-0.99), after controlling
      for differences in age and gender. For the incident population, treatment was
      significantly more likely for persons with diabetes (OR 1.14, 95% CI 1.04-1.26),
      CHD (OR 1.23 95% CI 1.08-1.39), and stroke (OR 1.21, 95% CI 1.04-1.42).
      CONCLUSIONS: Antidepressant medication use was somewhat higher in persons with
      medical co-morbidities, although these differences were small and inconsistent.

PMID- 18724573
TI  - Privatization in a publicly funded health care system: the U.S. experience.
AB  - The United States has four decades of experience with the combination of public
      funding and private health care management and delivery, closely analogous to
      reforms recently enacted or proposed in many other nations. Extensive research,
      herein reviewed, shows that for-profit health institutions provide inferior care
      at inflated prices. The U.S. experience also demonstrates that market mechanisms
      nurture unscrupulous medical businesses and undermine medical institutions unable
      or unwilling to tailor care to profitability. The commercialization of care in
      the United States has driven up costs by diverting money to profits and by
      fueling a vast increase in management and financial bureaucracy, which now
      consumes 31 percent of total health spending. The Veterans Health Administration
      system--a network of government hospitals and clinics--has emerged as the leader
      in quality improvement and information technology, indicating the potential for
      public sector excellence and innovation. The poor performance of U.S. health care
      is directly attributable to reliance on market mechanisms and for-profit firms,
      and should warn other nations from this path.

PMID- 18724574
TI  - Even higher global inequality than previously thought: a note on global
      inequality calculations using the 2005 International Comparison Program results.
AB  - Using the new results of the International Comparison Program 2005, the author
      reestimates inequalities between mean country incomes and global inequality among
      world citizens. All types of international inequality are found to be greater
      than previously thought (that is, as calculated using earlier data on countries'
      price levels). The main reason for the higher inequalities is that domestic price
      levels in most populous Asian countries (China, India, Philippines, Bangladesh)
      are some 40 percent higher than previously estimated. This implies not only
      higher global inequality but significantly greater global poverty head counts.

PMID- 18724575
TI  - Updated U.S. Congressional Budget Office data reveal unprecedented increase in
      inequality.
AB  - The U.S. Congressional Budget Office recently updated its authoritative data
      series on household incomes, 1979-2005. The new data reveal a sharp increase in
      income inequality over the past few years. The increase in income inequality
      (both pre- and post-tax), as measured by the change in the shares of income going
      to different income classes, was greater from 2003 to 2005 than over any other
      two-year period covered by the CBO data.

PMID- 18724576
TI  - Off target: a critical review of setting goals for reducing health inequalities
      in the United Kingdom.
AB  - Health policy in the United Kingdom is devolved to the four home countries.
      Nevertheless, England, Northern Ireland, Scotland, and Wales share a common
      commitment to reducing health inequalities and have set explicit targets in areas
      such as life expectancy, cancer mortality, long-standing illness, and smoking
      prevalence. However, many of the targets leave much to be desired in terms of
      their limited conceptual scope and their selection of methods and approaches. At
      one level this might be regarded as relatively unimportant. The mere fact of
      having health inequalities targets is laudable. But because the United Kingdom
      has been in the vanguard of research and policy development to reduce health
      inequalities, a critical appraisal of the strengths and weaknesses of the
      approaches adopted in the four home countries is timely. Following a description
      of the health inequalities targets, the article focuses on experiences in England
      and Scotland as examples of contrasting approaches to target setting and
      describes progress toward meeting targets in each country. The authors then
      outline key emerging issues in relation to developing targets and measuring
      progress, including conceptual dilemmas, biased reporting, implementation
      failure, and statistical fallacy.

PMID- 18724577
TI  - What can alienation theory contribute to an understanding of social inequalities
      in health?
AB  - This article examines both the contribution and the limitations of research that
      has sought to develop a causal understanding of the psychosocial dimension of
      inequalities in health. The article seeks to revive interest in Marx's theory of
      alienation in developing the case for an alternative materialist
      conceptualization that is able to postulate the pathways from alienation as a
      psychosocial generative structure to social inequalities in health outcomes
      within late modern societies.

PMID- 18724578
TI  - Public policy implications of tobacco industry smuggling through Native American
      reservations into Canada.
AB  - From 1980 to 1994, the Canadian government enacted major tax increases on tobacco
      products. These actions initiated significant tobacco smuggling from the United
      States into Canada through a few U.S. Native American reservations to undercut
      the price of Canadian tobacco products. The tobacco industry blamed rampant
      smuggling on excessive taxation; however, research shows that the tobacco
      industry had actually promoted smuggling schemes to both increase profits and
      provide an argument for tobacco taxation reduction. Although the smuggling has
      resulted in numerous U.S. and Canadian criminal convictions of tobacco industry
      officials and partners, significant smuggling continues throughout the world. For
      the few Native Americans involved, the smuggling was lucrative and they were able
      to avoid criminal prosecution through tribal sovereignty. Industry-supported
      tobacco smuggling has had a profoundly negative effect on Canadian public health
      that must be brought to light to prevent future similar occurrences.

PMID- 18724579
TI  - Under pressure, out of control, or home alone? Reviewing research and policy
      debates on the occupational health and safety effects of outsourcing and home
      based work.
AB  - The practice of outsourcing or subcontracting of work has grown rapidly in most
      countries over the past two decades. Outsourcing, de-institutionalization, and a
      range of other practices have also resulted in a growth of home-based work. Home
      based workers, even when not part of a subcontracting process, operate in an
      isolated situation remote from their employer and other workers. Do such work
      arrangements expose workers to greater risk of injury, illness, or assault? The
      authors reviewed international studies of the occupational health and safety
      (OHS) effects of subcontracting and home-based work undertaken over the past 20
      years. Of the 25 studies analyzed, 92 percent found poorer OHS outcomes. The
      studies were examined for clues about the reasons for these negative outcomes.
      The authors also identified similarities and differences between subcontracting
      and home-based work. Despite the evidence of poor OHS outcomes, research into
      outsourcing has stalled in recent years. With notable exceptions, governments
      have taken little account of findings on these work arrangements in their laws
      and policies, in part because neoliberal ideas dominate national and global
      policy agendas. The authors examine policy challenges and regulatory responses
      and make suggestions for future research and policy interventions.

PMID- 18724580
TI  - Clinical trials in Canada: whose interests are paramount?
AB  - More than 80 percent of clinical drug trials in Canada are funded by the
      pharmaceutical industry. This article evaluates the overall state of clinical
      trials in Canada and looks at the interplay between public and private interests.
      Health Canada has adopted standards developed by the International Conference on
      Harmonization, a body that is heavily influenced by industry. Commercial
      interests are increasingly involved in recruiting patients into clinical trials
      and in running these trials. It is in industry's interests to conduct drug tests
      on people for which it is easiest to see benefits. These interests are not
      fundamentally challenged by Health Canada's policy of issuing nonmandatory
      guidelines on who should and should not be included in clinical trials. The
      outcome of clinical trials is heavily influenced by commercial sponsorship, with
      the result that trials may favor corporate interests rather than the interests of
      the public. How Health Canada deals with that possibility is not known, because
      of its strict policy of treating clinical trial data as private property. If
      clinical trials are to serve the purpose for which they are designed, developing
      reliable and objective information about new drugs, then commercial interests
      cannot be allowed to take precedence over health interests.

PMID- 18724581
TI  - Chernobyl: an unbelievable failure to help.
AB  - The disaster at the Chernobyl power reactor near Kiev, which began on April 26,
      1986, was one of the world's worst industrial accidents. Yet the global
      community, usually most generous in its aid to a stricken community, has been
      slow to understand the scope of the disaster and reach out to the most devastated
      people of Ukraine, Belarus, and Russia. This article probes the causes of this
      confusion of perception and failure of response; clearly the problem is one of
      communication. Has the International Atomic Energy Agency betrayed the victims of
      the Chernobyl disaster because of its plans to promote the "peaceful atom"
      nuclear program in the developing world? Has the World Health Organization failed
      to provide clear, reliable information on the health effects resulting from the
      disaster? Are other historical problems or actors interfering with reasonable
      handling of the late effects of a nuclear disaster? Most importantly, what can be
      done to remedy this situation, to assist those most hurt by the late effects of
      Chernobyl and prevent such injustice in future? With the current promotion of
      nuclear energy as a "solution" to global climate change, we need to take a sober
      second look at the nuclear energy experiment and management of its hazards.

PMID- 18724582
TI  - A cultural critique of community psychiatry in India.
AB  - This article is the first comprehensive cultural critique of India's official
      community mental health policy and program. Data are based on a literature review
      of published papers, conference proceedings, analyses of official policy and
      popular media, interviews with key Indian mental health professionals, and
      fieldwork in Kanpur district, Uttar Pradesh (2004-2006). The authors demonstrate
      how three influences have shaped community psychiatry in India: a cultural
      asymmetry between health professionals and the wider society, psychiatry's search
      for both professional and social legitimacy, and WHO policies that have provided
      the overall direction to the development of services. Taken together, the
      consequences are that rural community voices have been edited out. The authors
      hypothesize that community psychiatry in India is a bureaucratic and culturally
      incongruent endeavor that increases the divide between psychiatry and local rural
      communities. Such a claim requires sustained ethnographic fieldwork to reveal the
      dynamics of the gap between community and professional experiences. The
      development of culturally sensitive psychiatric theory and clinical services is
      essential to improve the mental health of rural citizens who place their trust in
      India's biomedical network.

PMID- 18724583
TI  - State health reform flatlines.
AB  - Massachusetts' recent health reform has generated laudatory headlines and a
      flurry of interest in state-based initiatives to achieve universal health
      insurance coverage. In 1988, a similar Massachusetts effort was also acclaimed
      and was imitated by several other states. Unfortunately, none of those efforts
      can be judged a success. The authors briefly review this earlier experience and
      caution against premature declaration of victory.

PMID- 18724584
TI  - The ethics of supplier relations. ACHE's Ethical Policy Statements highlight
      this, other pressing ethical issues.

PMID- 18724585
TI  - Building partnerships: addressing overuse, underuse and misuse of care.

PMID- 18724586
TI  - Innovations in medical staff planning: setting the stage for the future.

PMID- 18724587
TI  - Rising from the ashes. Fallujah's healthcare at center of transformation.

PMID- 18724588
TI  - A commitment to lifelong learning. A history of ACHE's educational programming
      and the education of the hospital administrator.

PMID- 18724589
TI  - Ethics and quality improvement. Quality care and ethical principles cannot be
      separated when considering quality improvement activities.

PMID- 18724590
TI  - Putting patients first. Helping patients make care decisions through education.

PMID- 18724591
TI  - Making the transition. How FQHCs help hospitals and the communities they serve.

PMID- 18724592
TI  - Changes possible to area wage index. Hospitals should pay close attention for
      possible revision of methodology.

PMID- 18724593
TI  - Building business know-how through simulation. Hands-on tools can optimize
      financial learning among nonfinancial staff.

PMID- 18724594
TI  - Should physicians serve on the board? Hospital-physician partnerships may need to
      be closely reviewed.

PMID- 18724595
TI  - A new challenge in patient safety. Transforming leadership infrastructure through
      widespread board engagement.

PMID- 18724596
TI  - Succeeding in the healthcare market. Making sure your organization thrives now
      and in 2011.

PMID- 18724597
TI  - 'Sic transit gloria mundi'.

PMID- 18724598
TI  - Recognition and management of transient ischaemic attack.

PMID- 18724599
TI  - Malnutrition in various care settings in the UK: the 2007 Nutrition Screening
      Week Survey.

PMID- 18724600
TI  - Can the UK guidelines for stroke be effective? Attitudes to the symptoms of a
      transient ischaemic attack among the general public and doctors.
AB  - This questionnaire-based study assessed the attitudes of the general public to
      the symptoms of a transient ischaemic attack (TIA) and determined the current
      level of knowledge about the management of TIA among doctors. The public chose to
      wait for symptom recurrence before seeking medical advice for amaurosis (41%) and
      upper limb (UL) monoparesis (51%), sensory loss (68%), or paraesthesia (95%).
      However, medical advice would be sought most often for slurred speech alone (89%)
      or combined with UL monoparesis (99%). Most physicians confirmed that these
      symptoms could represent a 'carotid TIA' but many considered diverse symptoms as
      relevant. While most general practitioners would prescribe anti-platelet therapy,
      22-40% would not refer first-time TIA patients, depending upon the presenting
      symptom. In conclusion, the general public does not recognise the importance of
      TIA symptoms and the need for rapid assessment. This is compounded by
      deficiencies in the medical management of TIA. Stroke guidelines will remain
      ineffective without public awareness campaigns and physician education.

PMID- 18724601
TI  - Physician revalidation in Europe.
AB  - Despite the increasing attention on patient mobility, there remains a lack of
      European-level interest in assuring the sustained competence of health
      professionals. Specifically, the existing European legal framework fails to
      recognise the introduction of periodic revalidation and requirements to
      participate in continuing professional development in some countries. This study
      shows that the definitions and mechanisms of revalidation vary significantly
      across member states. While some countries, eg Austria, Germany and Spain, look
      to continuing medical education as a means to promote recertification and quality
      of care, other countries, eg Belgium, France and the Netherlands, also
      incorporate peer review. In the UK the proposed revalidation scheme would include
      elements of relicensure through appraisal and feedback as well as physician
      recertification. Divergence between countries also exists in monitoring and
      enforcement. The European Commission should explore the implications for
      professional mobility of the diversity in the regulation of the medical
      profession.

PMID- 18724602
TI  - The conflict between specialist diabetes services and acute-general internal
      medicine for consultant diabetologists in the UK in 2006.
AB  - An online survey of consultant diabetologists in the UK examined the interface
      between specialist services and acute-general internal medicine (acute-GIM). Out
      of 592 consultants, 289 (49%) responded. Of these, 94% contributed to acute-GIM,
      devoting equivalent time to acute-GIM and specialist diabetes services. Of the
      respondents, 10% provided a single-handed specialist service and 78% provided
      endocrine services. The survey found the input to acute-GIM was increasing,
      partly because other specialties were opting out. The increased commitment to
      acute-GIM compromised specialist diabetes activity through reduced consultant and
      training-grade time for outpatient activity and service development. The shift to
      primary care of chronic disease led to further conflict between acute-GIM and
      delivery of a specialist service, given the current systems for provision of
      consultant-led care. The large number of specialist trainees in diabetes and
      endocrinology will require innovative commissioning mechanisms that reflect the
      need to sustain and develop specialist diabetes and endocrine care in the
      appropriate settings as well as the continued input in acute trusts for acute
      GIM.

PMID- 18724603
TI  - Clinical update: melatonin and sleep disorders.
AB  - The hormone melatonin is increasingly used for the treatment of certain sleep
      disorders, particularly those related to disturbed biological rhythms. This
      article summarises current knowledge of its mechanism of action and identifies
      situations where there is good evidence for its efficacy. The authors provide
      advice, based on their own experience and consistent published data, concerning
      the dose range of melatonin to be used and the critically important question of
      the timing of treatment. Anecdotal evidence for the use of melatonin needs to be
      replaced by data from well-controlled, preferably multi-centre, randomised
      clinical trials.

PMID- 18724604
TI  - Cardiovascular disease--the silent killer in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a multisystem disease with high rates of morbidity
      and mortality. In recent years, there has been increasing focus on the growing
      rates of cardiovascular disease (CVD) in RA, over and above expected levels
      allowing for 'traditional' risk factors. In this paper the impact of CVD in RA,
      the relative contributions of traditional risk factors and novel risk factors
      (including homocysteine, oxidised low-density lipoprotein, high-sensitivity C
      reactive protein and leptin), and the need to address cardiovascular risk in the
      fight against premature death from coronary artery and stroke disease in RA are
      discussed.

PMID- 18724605
TI  - Trends in hospital admissions for pulmonary embolism in England: 1996/7 to
      2005/6.
AB  - Pulmonary embolism (PE) can be difficult to diagnose and manage. This paper
      examines recent national trends in admission rates and mortality for PE to help
      inform clinical practice. Admissions to NHS hospitals in England between 1 April
      1996 and 31 March 2006 were studied. Trends in admission rates, the proportion of
      all admissions with PE as primary or secondary diagnosis and hospital mortality
      following PE identified. There were 251,449 admissions with a diagnosis of
      pulmonary embolus in the study period. Non-elective admission rates rose from
      28.0 per 100,000 in 1996/7 to 32.1 per 100,000 in 2005/6. There was a significant
      increase in secondary diagnosis rates and a clear seasonal pattern with excess
      admissions in winter. There was significant in-hospital mortality for both
      primary (13%) and secondary diagnosis (31%). Mortality decreased over time and
      was highest among the elderly. Pulmonary embolism is associated with a
      significant mortality although overall trends in mortality are improving in
      England. Age and comorbidities must be considered when developing guidelines and
      individual treatment plans.

PMID- 18724606
TI  - Screening for pain in patients with cognitive and communication difficulties:
      evaluation of the SPIN-screen.
AB  - ABSTRACT - The scale of pain intensity (SPIN)-screen is a simple visual tool for
      the screening and measurement of pain intensity, which is designed to be
      accessible by patients with cognitive and communication problems. It was applied
      prospectively in a consecutive cohort of 79 patients admitted to a tertiary
      specialist neurorehabilitation unit, of which 86% had significant
      cognitive/communicative disabilities. In all, 71 patients (90%) responded to the
      SPIN. Concurrent validation against a standard numbered graphic rating scale
      (NGRS) showed a strong overall correlation (rho 0.94 p < 0.0001). When the NGRS
      was converted to an equivalent six-point scale, weighted Kappa tests demonstrated
      'almost perfect' agreement (K = 0.81, SE 0.083) between the two sets of ratings.
      Repeat testing after 24 hours provided preliminary evidence for the stability and
      responsiveness of the SPIN-screen, but these require further evaluation. Of those
      who expressed a preference for one tool over the other, 70% preferred the SPIN.
      The study provides support for application of the SPIN-screen as a routine
      screening tool in this group of patients.

PMID- 18724607
TI  - Iraq: the environmental challenge to HM land forces.
AB  - In 2003, occasional military patients with hyponatraemia, hypokalaemia and
      alkalosis were encountered in Iraq. Development of central pontine myelinolysis
      in one patient indicated treatment should be cautious. Two years later, heat
      illness continued to occur during the very hot summer months and 23 cases were
      admitted to a British military field hospital near Basra, Iraq. Incidence was <
      0.15% of deployed personnel per summer month. Serum sodium and potassium
      concentrations were directly (r = 0.66, p = 0.0002) and serum sodium and
      bicarbonate concentrations inversely (r= -0.64, p = 0.002) correlated. The
      magnitude of these changes was unrelated to the glomerular filtered load of
      sodium. While blood pressure was undiminished, estimated glomerular filtration
      rate was reduced. These electrolyte changes were compatible with secondary
      hyperaldosteronism but field conditions constrained further investigation.
      Hyponatraemia was probably due to salt deficiency rather than overhydration. In
      some military personnel summer salt supplementation could be essential during
      operations in hot countries.

PMID- 18724608
TI  - Shostakovich versus the Central Committee: the power of music.
AB  - The centenary of Shostakovich's birth, celebrated in 2006, generated considerable
      interest in his life and music. During the Cold War his music was rarely played
      in the West, and it was not until after his death in 1975 that it re-emerged. The
      publication of his memoirs in the UK, in 1979, gave new insights into his life in
      Soviet Russia. Music, like art and literature, has the power to shock and can
      reflect anger and frustration at contemporary social issues. Much debate has
      focused on whether Shostakovich was a victim or mouthpiece of Communism. In order
      to fully appreciate his music, it is essential to understand his personal and
      professional life under Josef Stalin--in particular his public humiliation by the
      Central Committee, and by professional musicians who were Communist Party
      members.

PMID- 18724609
TI  - Neurology of musical performance.
AB  - Performing music at a professional level requires the integration of multimodal
      sensory and motor information and precise monitoring of the performance via
      auditory feedback. In the context of Western classical music, musicians are
      forced to reproduce highly controlled movements almost perfectly with a high
      reliability. These specialised sensorimotor skills are acquired during extensive
      training periods over many years. The superior skills of musicians are mirrored
      in functional and structural plastic adaptations of sensorimotor and auditory
      systems of the brain. Auditory-sensorimotor integration, for example, is
      accompanied by rapid modulations of neuronal connectivity in the time range of 20
      minutes. Finally, dysfunctional plasticity in musicians, known as musician's
      dystonia, leads to deterioration of extensively trained fine motor skills.
      Musician's dystonia may be caused by training induced dysplasticity with
      pathological fusion of central nervous representations in sensorimotor cortical
      and subcortical brain regions.

PMID- 18724610
TI  - Gastroenterology.

PMID- 18724611
TI  - Irritable bowel syndrome--the new inflammatory bowel disease?

PMID- 18724612
TI  - Does Helicobacter pylori protect against oesophageal adenocarcinoma, and if so,
      how?

PMID- 18724613
TI  - Personality disorder and public mental health.
AB  - The diagnosis of personality disorder often appears to tell as much about the
      diagnoser as the diagnosed. For many it describes those who are deemed personally
      offensive, and as such it is not so much a diagnosis as a value judgment, the
      product of a negative interaction between two people that is given spurious
      respectability by a medical label. It is argued that these attitudes constitute a
      disastrous misperception of the truth, as personality disturbance (diathesis) in
      its many forms, including the unsatisfactory term 'disorder', is a highly
      significant contributor to human misery and handicap and a major cost to public
      mental health. It achieves this sorry record largely through stealth, because the
      current categorical system fails to embrace the breadth and heterogeneity of
      abnormal personality and the notion of offensive immutability makes the diagnosis
      a stigmatic one. This can be avoided by recoding personality in terms of
      severity. New treatments are now beginning to show evidence of efficacy and it is
      not unreasonable to hope that a condition that has been muttered about for years
      in parentheses will now be better recognised and defined, exposed without
      misunderstanding, and managed appropriately and well.

PMID- 18724614
TI  - Hubris syndrome.
AB  - Hubris syndrome is associated with power, more likely to manifest itself the
      longer the person exercises power and the greater the power they exercise. A
      syndrome not to be applied to anyone with existing mental illness or brain
      damage. Usually symptoms abate when the person no longer exercises power. It is
      less likely to develop in people who retain a personal modesty, remain open to
      criticism, have a degree of cynicism or well developed sense of humour. Four
      heads of government in the last 100 years are singled out as having developed
      hubris syndrome: David Lloyd George, Margaret Thatcher, George W Bush and Tony
      Blair.

PMID- 18724615
TI  - Epilepsy: a review of reports, guidelines, recommendations and models for the
      provision of care for patients with epilepsy.
AB  - Epilepsy is common and has a variety of causes and associated pathologies.
      Increased understanding of the pathophysiology underlying the epilepsies and
      advances in classification, diagnostic imaging and drug treatments have led to a
      reduction in stigma and growing demand for services to be improved for patients.
      A number of important reports and guidelines have emerged in the UK in recent
      years, which are summarised here. Diagnosis, classification, management and
      models of care are discussed as well as the management of drug intractable
      seizures, status epilepticus, and approaches to special patient groups: women in
      the fertile years, the elderly and those with learning difficulties.

PMID- 18724616
TI  - Acute non-myelosuppressive complications of systemic anticancer therapy.

PMID- 18724618
TI  - Chemotherapy induced febrile neutropenia: management and prevention.

PMID- 18724617
TI  - Contemporary management of hepatocellular carcinoma.

PMID- 18724619
TI  - Cancer of unknown primary site.

PMID- 18724620
TI  - Angiogenesis as a therapeutic target in cancer.

PMID- 18724621
TI  - Balancing the risk of chronic gastrointestinal bleeding and thromboembolic events
      in a patient with a metallic aortic valve.

PMID- 18724622
TI  - Respiratory problems on the acute take: pleural disease and acute dyspnoea.

PMID- 18724623
TI  - A system for prescribing oral potassium supplements.

PMID- 18724625
TI  - The exercise pill.

PMID- 18724624
TI  - Impact of centralisation of specialist services on sister hospital specialty
      opinion demand and consultant job plans.

PMID- 18724626
TI  - Positive action would take institute forward. Interview by Nicholas Marshall.

PMID- 18724627
TI  - Ergonomic operating department design.
AB  - The conclusions of an in-depth German study into the optimal design of operating
      rooms and their associated storage / auxiliary facilities are examined by Sonja
      Koneczny, Dipl.-Ing.(FH), M.Sc., of the Experimental-OR and Ergonomics
      Department, University Hospital Tuebingen, Germany.

PMID- 18724628
TI  - Role is far from child's play.
AB  - Mike Ralph, Great Ormond Street Hospital's estates and facilities director, tells
      Health Estate Journal editor Jonathan Baillie about his life-long passion for
      engineering, a varied career in health estate, the "ups and downs" of the
      profession, his worries for its future, and the challenge of providing continuity
      of care at a top children's hospital as a major redevelopment project takes shape
      at the site's heart.

PMID- 18724629
TI  - MPs consider UK engineering's future.
AB  - The Government's Parliamentary Innovation, Universities, Science and Skills
      Committee (IUSSC), which in January launched an enquiry into the current "state"
      of the UK engineering sector, recently held a session in Westminster to hear
      evidence on the topic from expert bodies. IHEEM chief executive John Long was
      among those to draft written evidence for the Committee that not only provides an
      overview of the current UK engineering sector and its major challenges, but also
      recommends ways to maximise engineers' contribution in the future.

PMID- 18724631
TI  - 'Enabling' a better health service.

PMID- 18724630
TI  - Scaling up Scandinavian style.
AB  - In March 2010 work is due to start on the largest hospital construction project
      in Denmark's history. Tom Danielsen, a partner at leading Scandinavian
      architectural practice CF Moller, part of the international consultancy team
      which won the commission for the New University Hospital in Aarhus last December,
      describes the thinking and philosophy behind a ground-breaking development set to
      be "the size of a small town".

PMID- 18724632
TI  - Patient is king in this healthcare realm.

PMID- 18724633
TI  - Engineered approach to fire safety.

PMID- 18724634
TI  - Radical approaches spotlighted.

PMID- 18724635
TI  - A holistic vision of primary care.
AB  - A classic illustration of how integrating healthcare facilities with, or very
      close to, wider public and community services in an ambitious primary care
      setting can benefit the community via added convenience and accessibility,
      simultaneously reducing pressure on local acute health services, was provided by
      two speakers at Health Service Journal's "Rebuilding the NHS" conference in
      London. Health Estate Journal reports.

PMID- 18724636
TI  - Copper removal from an effluent generated by a plastics chromium-plating industry
      using a rotating cylinder electrode (RCE) reactor.
AB  - This work shows the application of a rotating cylinder electrode (RCE) in the
      removal of Cu(II) content from an effluent generated by a plastics chromium
      plating industry, on the laboratory scale; in particular, it deals with rinse
      water from the electrolytic copper process. This process was designed to convert
      cupric ions in solution to metal powder. The generation of metal powders in the
      RCE was achieved at Reynolds numbers between 52925 and 83183 and limiting current
      densities (J(L)) in the range of 17 to 25 mA cm(-2). The removal of Cu(II)
      (initially 922 ppm) reached 43 ppm in 10 minutes of electrolysis for Re = 83183
      and J = 25 mA cm(-2), with a space-time yield of 88 mg Cu(II) L(-1) min(-1), 95%
      current efficiency, and energy consumption of 5.3 KWh m(-3). The electrochemical
      treatment applied to waste rinse water at the RCE allows this treated water to be
      recycled back to the same rinsing process, avoiding additional consumption and
      discharge of this liquid.

PMID- 18724637
TI  - Use of shredded tire chips and tire crumbs as packing media in trickling filter
      systems for landfill leachate treatment.
AB  - Scrap tire stockpiles are breeding grounds for pests, mosquitoes and west Nile
      viruses and, thereby, become a potential health risk. This experimental study was
      carried out in six stages to determine the suitability of shredded tire materials
      in a trickling filter system to treat landfill leachate. Biochemical oxygen
      demand (BOD5), chemical oxygen demand (COD) and NH3-N removals were obtained in
      the range of 81 to 96%, 76 to 90% and 15 to 68%, respectively. The removal of
      organics appears to be largely related to total dissolved solids reduction in
      leachate. A sudden increase, from time to time, in organic content of effluent
      could be attributed to biomass sloughing and clogging in the trickling filters.
      However, tire crumbs exhibited more consistent organics removal throughout the
      experimental program. Due to the high surface area of shredded tire chips and
      crumbs, a layer of biomass, 1-2 mm thick, was attached to them and was sloughed
      off at an interval of 21 days. Apart from that, as shredded tires are
      comparatively cheaper than any other usable packing material, tire chips and tire
      crumbs appeared to be quite promising as packing media in trickling filters for
      landfill leachate treatment.

PMID- 18724638
TI  - Performance of a high-rate/high-shear activated sludge bioreactor treating
      biodegradable wastewater.
AB  - A high-rate activated sludge (HRAS) bioreactor with high shear venturi aeration
      was operated in the laboratory at various organic loading rates to evaluate
      chemical oxygen demand (COD) removal efficiency and sludge production. Organic
      loading rates two orders of magnitude higher than conventional activated sludge
      loading were investigated in the modified HRAS reactor for a period of 41 weeks.
      Filtered COD removal efficiency varied from 81 to 92 % for organic loading rates
      of 3 to 85 kg COD m(-3) d(-1). Observed sludge yield was determined to be 0.10
      0.25 g TSS produced g(-1) COD removed, under hydraulic and solids retention times
      (SRTs) approaching less than two hours and two days, respectively. Observed
      sludge yield actually declined as loading increased and SRT decreased. It was
      concluded that high-shear forces created in the reactor due to intense aeration
      at high volumetric organic loading rates increased substrate utilization rate,
      improved filtered COD removal efficiency, and kept sludge yields relatively low
      (despite the very low operating SRTs).

PMID- 18724639
TI  - Sulfur formation and recovery in a thiosulfate-oxidizing bioreactor.
AB  - This work describes the design and performance of a thiosulfate-oxidizing
      bioreactor that allowed high elemental sulfur production and recovery efficiency.
      The reactor system, referred to as a Supernatant-Recycling Settler Bioreactor
      (SRSB), consisted of a cylindrical upflow reactor and a separate aeration vessel.
      The reactor was equipped with an internal settler and packing material
      (structured corrugated PVC sheets) to facilitate both cell retention and the
      settling of the formed elemental sulfur. The supernatant from the reactor was
      continuously recirculated through the aerator. An inlet thiosulfate concentration
      of 100 mmol l(-1) was used. The reactor system was fed with 89 mmol l(-1) d(-1)
      thiosulfate reaching 98 to 100% thiosulfate conversion with an elemental sulfur
      yield of 77%. Ninety-three percent of the produced sulfur was harvested from the
      bottom of the reactor as sulfur sludge. The dry sulfur sludge contained 87%
      elemental sulfur. The inclusion of an internal settler and packing material in
      the reactor system resulted in an effective retention of sulfur and biomass
      inside the bioreactor, preventing the oxidation of thiosulfate and elemental
      sulfur to sulfate in the aerator and, therefore, improving the efficiency of
      elemental sulfur formation and recovery.

PMID- 18724640
TI  - Methodologies for determining the bioavailability and biodegradability of
      sludges.
AB  - The measurement of sludge bioavailability and biodegradability is important to
      assess the sludge potential as a source of carbon and energy during its
      biological stabilization. As the majority of biological sludge (secondary sludge)
      consists of biomass, an increase in sludge bioavailability can be achieved by
      using different techniques for cell lysis, which is aimed at releasing
      intracellular organics into the bulk solution and enhancing hydrolysis of
      particulate organic matter. This paper reviews the main methodologies currently
      used for cell lysis, which include thermal, ultrasonic and chemical techniques
      and a combination of these, as well as the analytical procedures that can be
      employed to assess the degree of lysis and sludge solubilization. In addition,
      this paper also discusses common techniques that can be used for measuring the
      biodegradability of sludge under aerobic and anaerobic conditions.

PMID- 18724641
TI  - Use of coal mining waste for the removal of acidity and metal ions Al (III), Fe
      (III) and Mn (II) in acid mine drainage.
AB  - The coal industry may generate acid mine drainage (AMD) and mining wastes, which
      may adversely affect the quality of the environment. In this study we propose the
      use of this waste in the removal of acidity and metal ions, as well as in the
      reduction of the toxicity of AMD. A physico-chemical analysis of the waste shows
      the presence of mainly SiO2, Al2O3 and Fe2O3 and a superficial area of 4.316 m2
      g(-1). The treatment of AMD with the waste resulted in an increase in pH from 2.6
      to 7.8 and removed 100% of the Al (III), 100% of the Fe (III) and 89% of the Mn
      (II). We also observed that the high toxicity of the AMD towards Daphnia magna
      (LC50 = 3.68%) and Artemia sp. (LC50 = 4.97%) was completely eliminated after
      treatment with the waste. The data obtained allow us to propose that the waste
      can be used in the treatment of AMD, providing an economic use for the waste.

PMID- 18724642
TI  - The effect of sodium chloride on the denitrification of saline fishery
      wastewaters.
AB  - The effect of sodium chloride concentration (0.47-100 g l(-1)) on the rates of
      nitrate and nitrite reduction was studied at 37 degrees C and pH 7.5 in a batch
      reactor fed with a mixture (v/v) of salmon bloodwater and synthetic substrate and
      inoculated with biomass adapted to saline conditions (24 g NaCl per litre). NaCl
      inhibited the nitrate and nitrite reduction rates; the rates were increasingly
      inhibited at increasing NaCl concentrations in the studied concentration range.
      An empiric noncompetitive model adequately quantified the effect of NaCl on the
      rates of nitrate and nitrite reduction. The maximum reduction rate (R(D,max)) in
      a low salt medium and the inhibition constant (K(I)) were determined for each
      reductive step. The calculated kinetic parameters were R(D,max) = 25.5 +/- 0.74
      mg N (g VSS h)(-1) and K(I)= 34.9 +/- 2.34 x 10(-3) g l(-1) for nitrate reduction
      and R(D,max) = 18.7 +/- 1.05 mg N (g VSS h)(-1) and K(I) = 62.5 +/- 3.32 x 10(-3)
      g l(-1) for nitrite reduction. NaCl has a greater effect on nitrite reduction
      rate than on the nitrate reduction rate.

PMID- 18724643
TI  - Organic and nitrogenous matter effects on the denitrification of saline and
      protein-rich effluents.
AB  - The separate effect of protein concentration, nitrate concentration and
      carbon/nitrogen (C/N) ratio on the rate and efficiency of nitrate reduction was
      studied in batch reactors fed with a mixture of a synthetic substrate and a
      saline protein-rich salmon-plant effluent. At a constant nitrate concentration
      (40 mg L(-1)), the specific rate of nitrate removal decreased by 60% with
      increasing initial protein concentration (392 to 1900 mg L(-1)) and
      ammonification prevailed under these conditions; meanwhile at a constant protein
      concentration (1104 mg L(-1)), the specific rate of nitrate removal increased 58
      times with increasing nitrate concentrations (0.5 to 78 mg L(-1)) and
      denitrification was the main route for nitrate reduction. The C/N ratio had an
      inverse effect on the specific rate of denitrification; the latter ranged from
      227 to 563 [mg NO3(-)-N (g VSS d)(-1)] for a C/N ratio of 163 to 16 [mg TOC
      (total organic carbon) (mg NO3(-)-N)(-1)], respectively. On the other hand, the
      ammonia production rate was proportional up to a C/N ratio of 150.

PMID- 18724644
TI  - Development of PLS calibration models from UV-Vis spectra for TOC estimation at
      the outlet of a fuel park wastewater treatment plant.
AB  - In the present work ultraviolet (UV)-visible spectra of water samples collected
      at the outlet of a fuel park wastewater treatment plant, including biological
      treatment, were acquired and used for the development of partial least squares
      (PLS) calibration models for the fast and simple estimation of total organic
      carbon (TOC). Three different PLS models were developed and compared on the basis
      of a common spectral range. The first model was obtained using spectra of raw
      samples, the second using spectra of diluted samples, to assess signal saturation
      in the UV region, and the third using spectra of both diluted and raw samples, in
      order to expand the narrow interval of TOC concentration values present in the
      original dataset. The root mean squared error of cross-validation values for the
      developed PLS models were 2.3, 1.0 and 4.4 mg Cl(-1), respectively, and the
      validation results where highly satisfactory (root mean squared error of
      prediction values of 1.8, 0.8 and 4.5 mg Cl(-1), respectively).

PMID- 18724645
TI  - Aerobic treatment of landfill leachate using a submerged membrane bioreactor-
      prospects for on-site use.
AB  - Submerged membrane bioreactor (MBR) technology for aerobic treatment of landfill
      leachate was studied in laboratory scale to evaluate its potential for on-site
      use. Three combinations of solid retention time (SRT) - hydraulic retention time
      (HRT) of 60 days - 3.5 days, 60 days - 2 days and 30 days - 1 day, were examined
      to evaluate reactor performance under varying loading and biomass conditions.
      Chemical Oxygen Demand (COD) removal ranged from 54 to 78%, depending on the
      influent leachate source and loading conditions. The MBR showed excellent
      Biological Oxygen Demand (BOD5) removal of 97% and higher, even at HRT as low as
      1 day. Complete suspended solids retention and full nitrification of the incoming
      ammonia was observed despite highly variable loading. Significant removal of
      iron, lead, manganese, cadmium and aluminum was observed. No significant changes
      in the removal efficiency of metals, ammonia, and BOD5 were observed at different
      SRT-HRT. Toxicity removal decreased with increasing HRT. The produced effluent
      met current water quality guidelines for discharge into natural streams in
      Manitoba.

PMID- 18724646
TI  - A critical review on the process of contaminant removal in Fe0-H2O systems.
AB  - A central aspect of the contaminant removal by elemental iron materials (Fe0 or
      Fe0 materials) is that reduction reactions are mediated by the iron surface
      (direct reduction). This premise was introduced by the pioneers of the reactive
      wall technology and is widely accepted by the scientific community. In the
      meantime enough evidence has been provided to suggest that contaminant reduction
      through primary corrosion products (secondary reductants) does indeed occur
      (indirect reduction). It was shown for decades that iron corrosion in the pH
      range of natural waters (4-9) inevitably yields an obstructive oxide film of
      corrosion products at the metal surface (oxide film). Therefore, contaminant
      adsorption on to corrosion products and contaminant co-precipitation with
      corrosion products inevitably occurs. For adsorbed and coprecipitated
      contaminants to be directly reduced the oxide film should be electronic
      conductive. This study argues through a literature review a series of points
      which ultimately lead to the conclusion that, if any quantitative contaminant
      reduction occurs in the presence of Fe0 materials, it takes place within the
      matrix of corrosion products and is not necessarily a direct reduction. It is
      concluded that Fe0 materials act both as source of corrosion products for
      contaminant adsorption/coprecipitation and as a generator of FeII and H2 (H) for
      possible catalytic contaminant reduction.

PMID- 18724647
TI  - Decolorization of a mixture of textile dyes using Bjerkandera sp. BOL-13.
AB  - The white-rot fungus Bjerkandera sp. BOL-13 was evaluated regarding
      decolorization of four textile dyes Reactive blue 21, Reactive black 5, Reactive
      orange 13 and Reactive yellow 206. Experiments were performed in batch and
      continuous modes. The total dye concentration in all experiments was 100 mg l(
      1). The results of the batch experiments showed that the fungus decolorized all
      dyes but at different rates. There was, however, an increase in the ultraviolet
      (UV) absorbance when a medium with a low concentration of nitrogen was used. No
      increase in UV range was observed when the nitrogen concentration was increased.
      A continuous experiment was performed to study the decolorization of a mixture of
      three of the dyes Reactive blue 21, Reactive black 5 and Reactive orange 13.
      Scanning of inlet and outlet samples showed that the absorbance at the peaks in
      the visible range decreased by 60-66%. The UV absorbance of the outlet increased
      during the first days of operation after which it decreased again to reach the
      same level as the inlet. The hydraulic retention time in the reactor was 3 days.
      The medium containing the higher nitrogen concentration was used in the
      continuous experiment.

PMID- 18724648
TI  - Tretinoin microsphere gel in facial acne vulgaris: a meta-analysis.
AB  - BACKGROUND: Acne vulgaris can persist beyond adolescence into the fourth decade
      of life or later; most patients have a combination of inflammatory and
      noninflammatory lesions. OBJECTIVE: To determine whether tretinoin microsphere
      gel (TMG) 0.04% applied once nightly is well tolerated and effective in reducing
      inflammatory and noninflammatory lesions in adolescents and adults with mild to
      moderate facial acne. METHODS: The results of 3 randomized, double-blind, vehicle
      controlled studies of TMG 0.04% applied once nightly for 12 consecutive weeks in
      a total of 629 patients, ages 11 to 49 years, were combined. Reductions in acne
      lesion counts were assessed twice monthly, and an investigator's global
      evaluation (IGE) was performed at the study endpoint (week 12). RESULTS:
      Tretinoin microsphere gel 0.04% was significantly superior to the vehicle gel in
      reducing both inflammatory and noninflammatory lesions over the 12-week treatment
      period, and produced a higher successful treatment rate than the vehicle gel, as
      judged by IGE ratings at week 12. The most frequent adverse events were erythema,
      peeling, and dryness, which were mostly mild and occurred in 59.7% to 63.3% of
      patients with TMG 0.04%, as compared with 26.9% to 51.0% of patients with the
      vehicle gel (placebo). CONCLUSION: The TMG 0.04% formulation is significantly
      superior when compared to its vehicle gel in reducing inflammatory and
      noninflammatory acne lesions over a period of 12 weeks and is well tolerated.

PMID- 18724649
TI  - Tretinoin microsphere gel in younger acne patients.
AB  - BACKGROUND: Facial acne is common in adolescents and can have a significant
      psychosocial impact. Treatments prescribed should not add stress by causing
      excessive localized irritation. OBJECTIVE: To determine whether the lowest
      concentration of tretinoin microsphere gel (TMG) currently available (0.04%)
      provides an acceptable balance of efficacy and tolerability for adolescents with
      moderate facial acne. METHODS: The findings of 2 multicenter, randomized, double
      blind, vehicle-controlled trials of TMG 0.04% applied once nightly for 12 weeks
      in 245 adolescents ages 11 to 16 years with moderate facial acne were combined.
      Patients were evaluated via changes in acne lesion counts and the occurrence of
      cutaneous and other adverse effects. RESULTS: Tretinoin microsphere gel 0.04%
      reduced total, noninflammatory, and inflammatory lesion counts to a significantly
      greater extent than the vehicle gel at 12 weeks (P<.000005). The mean percentage
      reductions in noninflammatory and inflammatory lesion counts at 12 weeks in
      females were 45.0% and 51.4%, respectively; and in males, 20.5% and 36.7%,
      respectively. Tretinoin microsphere gel 0.04% was tolerated well, with over 70%
      of patients experiencing no cutaneous adverse events (AEs). CONCLUSION: Tretinoin
      microsphere gel 0.04% is effective in significantly reducing all types of acne
      lesions in adolescents with moderate facial acne ages 11 to 16 years, and has a
      low incidence of cutaneous AEs.

PMID- 18724650
TI  - Cumulative irritation potential of topical retinoid formulations.
AB  - BACKGROUND: Localized irritation can limit treatment success with topical
      retinoids such as tretinoin and adapalene. The factors that influence irritant
      reactions have been shown to include individual skin sensitivity, the particular
      retinoid and concentration used, and the vehicle formulation. OBJECTIVE: To
      compare the cutaneous tolerability of tretinoin 0.04% microsphere gel (TMG) with
      that of adapalene 0.3% gel and a standard tretinoin 0.025% cream. METHODS: The
      results of 2 randomized, investigator-blinded studies of 2 to 3 weeks' duration,
      which utilized a split-face method to compare cumulative irritation scores
      induced by topical retinoids in subjects with healthy skin, were combined. Study
      1 compared TMG 0.04% with adapalene 0.3% gel over 2 weeks, while study 2 compared
      TMG 0.04% with tretinoin 0.025% cream over 3 weeks. RESULTS: In study 1, TMG
      0.04% was associated with significantly lower cumulative scores for erythema,
      dryness, and burning/stinging than adapalene 0.3% gel. However, in study 2, there
      were no significant differences in cumulative irritation scores between TMG 0.04%
      and tretinoin 0.025% cream. Measurements of erythema by a chromameter showed no
      significant differences between the test formulations in either study.
      CONCLUSION: Cutaneous tolerance of TMG 0.04% on the face was superior to that of
      adapalene 0.3% gel and similar to that of a standard tretinoin cream containing a
      lower concentration of the drug (0.025%).

PMID- 18724651
TI  - Photographic assessment of tretinoin microsphere gel in moderate acne.
AB  - BACKGROUND: True objective measures for assessing responsiveness to acne
      treatments are lacking. Photographic documentation can therefore be a valuable
      adjunct to treatment assessment. OBJECTIVES: To photographically document the
      ability of tretinoin microsphere gel (TMG) 0.1% in improving facial acne.
      METHODS: A standardized photographic technique was used to assess the efficacy
      and tolerability of TMG 0.1% applied once nightly for 12 weeks in an open-label
      trial involving 30 patients (Caucasian and Hispanic) ages 11 to 40 years with
      moderately severe facial acne. RESULTS: An assessment of frontal, left-sided, and
      right-sided color photographs at week 12 indicated that TMG 0.1% reduced total,
      noninflammatory, and inflammatory acne lesion counts by 47.8%, 53.5%, and 33.2%,
      respectively; and produced an "excellent/ good" investigator's global evaluation
      (4-point scale) treatment response in 63.6% of patients. Tretinoin microsphere
      gel 0.1% was well tolerated, and more than 63% of subjects did not exhibit
      cutaneous adverse effects at week 12. CONCLUSIONS: The standardized photographic
      technique proved to be a useful tool for documenting the efficacy of TMG 0.1% in
      consistently and significantly improving moderately severe facial acne over a 12
      week treatment period.

PMID- 18724652
TI  - Quality of web-based information on cannabis addiction.
AB  - This study evaluated the quality of Web-based information on cannabis use and
      addiction and investigated particular content quality indicators. Three keywords
      ("cannabis addiction," "cannabis dependence," and "cannabis abuse") were entered
      into two popular World Wide Web search engines. Websites were assessed with a
      standardized proforma designed to rate sites on the basis of accountability,
      presentation, interactivity, readability, and content quality. "Health on the
      Net" (HON) quality label, and DISCERN scale scores were used to verify their
      efficiency as quality indicators. Of the 94 Websites identified, 57 were
      included. Most were commercial sites. Based on outcome measures, the overall
      quality of the sites turned out to be poor. A global score (the sum of
      accountability, interactivity, content quality and esthetic criteria) appeared as
      a good content quality indicator. While cannabis education Websites for patients
      are widespread, their global quality is poor. There is a need for better evidence
      based information about cannabis use and addiction on the Web.

PMID- 18724653
TI  - Does the impact of anti-drinking and driving Public Service Announcements differ
      based on message type and viewer characteristics?
AB  - The purpose of this study was to inform future Public Service Announcement (PSA)
      development by examining the potential effectiveness of different types of anti
      driving under the influence (DUI) PSAs for persons with different
      characteristics. PSAs utilizing empathy, fear, and informational approaches were
      shown to persons recruited from psychology courses (n = 137) and individuals that
      were mandated to treatment following a DUI offense (n = 17). The empathy approach
      was perceived to be the most effective and evoked the most negative affect,
      followed by fear and informational approaches. Less experience with DUI, lower
      sensation seeking, higher motivation to change, and higher perception of
      dangerousness of DUI all emerged as good predictors of higher perceived
      effectiveness of anti-DUI PSAs. Gender differences in perceived effectiveness
      were examined for fear and empathy PSAs, with inconclusive findings.

PMID- 18724654
TI  - Predicting ecstasy use among young people at risk: a prospective study of
      initially ecstasy-naive subjects.
AB  - Our aim is to identify predictors of first-time ecstasy use in a prospective
      study among young people at risk. As part of the multidisciplinary Netherlands
      XTC Toxicity Study (NeXT), we monitored 188 subjects aged > or = 18 who were
      ecstasy-naive at baseline but seemed likely to start taking ecstasy in the near
      future. After an 11- to 26-month follow-up period, 160 respondents remained
      (85.1%; mean age 21.0 years, 58.1% females): 65 who took ecstasy at least once
      (ecstasy users) and 95 non-users. At baseline and four times during follow-up,
      respondents completed self-report questionnaires. Cox regression analysis was
      used to examine the effects of baseline respondent characteristics on incident
      ecstasy use. Development of peer group ecstasy use was analyzed by logistic
      regression. Intention to use ecstasy, low education, and current weekly cannabis
      use independently increased the hazard rate for first ecstasy use. Although
      ecstasy use among peers at baseline was not a predictor, the proportion of
      ecstasy users with ecstasy-using peers increased markedly during the study. Our
      results suggest that targeted prevention activities should focus in particular on
      young people who have strong intentions to take ecstasy, especially if they are
      also regular smokers of cannabis.

PMID- 18724655
TI  - Prevention of methamphetamine abuse: can existing evidence inform community
      prevention?
AB  - Little research exists on effective strategies to prevent methamphetamine
      production, distribution, sales, use, and harm. As a result, prevention
      practitioners (especially at the local level) have little guidance in selecting
      potentially effective strategies. This article presents a general causal model of
      methamphetamine use and harms that reflects the available findings from either
      research specific to methamphetamine or from alcohol and other illegal drugs, and
      suggests prevention approaches and strategies that communities might use based
      upon research evidence and experience. Community methamphetamine prevention can
      use the public health and safety perspective applied to other substance abuse
      prevention. Analyses of the complex system of intermediate variables that
      interact to affect methamphetamine use and harms suggest that multiple
      reinforcing prevention interventions may have the greatest potential
      effectiveness.

PMID- 18724656
TI  - Substitute addiction: a concern for researchers and practitioners.
AB  - An understanding of the role of substitute addictions remains unclear. This
      article examines the range and possible reward functions of substitute
      addictions. We suggest that prevention education and treatment need to take into
      account substitute addictions as an influential aspect ofrecovery. Research is
      needed to better understand the prevalence and functions of, and solutions to
      substitute addictions.

PMID- 18724658
TI  - [Developments of microfluidic chip-based capillary electrophoresis for protein
      separation].
AB  - In this paper, the developments of microfluidic chip-based capillary
      electrophoresis (CE) for protein separation in recent years are reviewed. Various
      chip-based CE systems for protein separation based on different CE separation
      modes are introduced. The approaches to suppress the adsorption of proteins on
      the surface of microchannel on chips are discussed. The application prospect for
      chip-based CE in protein separation is also proposed. Forty-seven references are
      cited.

PMID- 18724659
TI  - [Free flow electrophoresis and its application development].
AB  - The principal, separation modes, influence factors and the equipment development
      of free flow electrophoresis (FFE) are introduced. Its latest applications on
      ion, small molecule and particles separation, peptides and proteins separation,
      cells and organelles separation, enantiomers separation, microchip device and
      proteomics are reviewed with cited 73 papers.

PMID- 18724657
TI  - Adoption of evidence-based practices among substance abuse treatment providers.
AB  - This research was conducted at a Substance Abuse Forum designed to address local
      community needs by focusing on Evidence-Based Practices (EBPs) in addiction
      treatment. The purpose of the study was to assess substance abuse treatment
      professionals' readiness to adopt EBPs, experience with EBPs, and attitudes
      toward EBPs, as well as agency support for EBPs. A total of 119 addiction
      treatment providers completed pre-test measures, and 82% completed a post-test.
      Eighty-three percent of participants reported using some EBPs in the past year,
      and 75% reported currently using EBPs. Participants who were currently licensed
      or certified in addictions had less negative attitudes toward EBPs than those
      without credentials. While respondents reported agency support for EBPs, most
      expressed interest in further training. This study underscores the movement
      toward EBPs in addiction treatment and the need for effective dissemination and
      training in this area.

PMID- 18724660
TI  - [Simultaneous determination of 14 phthalate ester residues in animal innards by
      gas chromatography-mass spectrometry with electron impact ionization].
AB  - An analytical multiresidue method was developed for the simultaneous
      determination of 14 phthalate esters (PAEs) in animal innards by gas
      chromatography-mass spectrometry with electron impact ionization (GC-EI/MS).
      After the optimization of different parameters such as the extraction solvent,
      PAEs were extracted from animal innards with hexane-dichloromethane (1:1, v/v) in
      an ultrasonic bath and cleaned up on a Florisil column, then were determined by
      GC-EI/MS in selected ion monitoring mode with diphenyl phthalate (DPhP) as
      internal standard. The recovery studies were performed at 100, 200 and 400
      microg/kg levels for each PAE, and the recoveries ranged from 60% - 110% with the
      relative standard deviations between 0.8% and 10.3% for different PAEs. The
      detection limit of the method was less than 1.74 microg/kg for most of PAEs
      except dimethoxyethyl phthalate (DMEP) and di(2-ethoxyethyl) phthalate (DEEP).
      The method was linear over the range of 50.0 - 800.0 microg/kg with the
      correlation coefficients larger than 0.999 4. The method has been successfully,
      applied to the determination of 14 PAEs in six animal innards.

PMID- 18724661
TI  - [Rapid determination of volatile flavor compounds in soy sauce using head space
      solid-phase microextraction and gas chromatography-mass spectrometry].
AB  - A rapid and simple method was developed for the determination of volatile flavor
      compounds (VFCs) in soy sauce by head space solid-phase microextraction (HS-SPME)
      coupled to capillary gas chromatography-mass spectrometry (GC-MS). Five types of
      SPME fibers, including 85 microm PA, 100 microm PDMS, 75 microm CAR/PDMS, 65
      microm PDMS/DVB, 50 microm DVB/CAR/PDMS were investigated. Three parameters for
      HS-SPME in terms of adsorption time, salt concentration, and extraction
      temperature were optimized. Adsorption time tested in this study were 20, 40 and
      60 minutes; the salt concentrations were 180, 210, 250, 270 and 300 g/L; and
      extraction temperatures were 25, 35, 45, 55 and 65 degrees C. The concentrations
      of the compounds were calculated based on their relative peak areas to the
      internal standard of 2-octanol. An 85 microm PA fiber, adsorption time of 40 min,
      a temperature of 45 degrees C and NaCl concentration of 250 g/L were selected as
      th optimum conditions. This optimized method was applied to evaluate a real
      sample. As a result, 97 compounds in a soy sauce sample were isolated and
      identified successfully. The results showed that alcohols, carboxylic acids,
      esters and phenols were the major VFCs of soy sauce. The most important groups of
      volatile compounds in the soy sauce sample were ethanol, hexadecanoic acid,
      phenylethyl alcohol and 2,3-butanediol. In addition, some oxo-compounds and
      heterocyclic compounds were also found. The average relative standard deviation
      of the relative peak area was 12.1%, and the recoveries were 79.9% - 109.6%. The
      method is simple, fast and accurate with high reproducibility, high sensitivity
      and low cost.

PMID- 18724662
TI  - [Two sample pretreatment methods and their applications in the determination of
      111 pesticides and related chemicals in aquatic products].
AB  - Two sample pretreatment methods were developed and applied to determine 111
      residues of pesticides in aquatic products. For Method I, the residues were
      extracted from homogenized tissue with acetone-ethylacetate-n-hexane (1 : 1 : 1,
      v/v/v), and then were redissolved in acetonitrile; for Method II, the residues
      were extracted from homogenized tissue with acetonitrile - water under
      ultrasonication, and then were separated by liquid-liquid partition. The
      supernatants were purified using solid phase extraction (Envi-18 and PSA columns)
      prior to the GC-MS analysis. The determination was performed in selected ion
      monitoring (SIM) mode with the external calibration for quantitative analysis.
      Under the optimal conditions, the detection limits (S/N = 3) for residues of
      pesticides were in the ranges of 0.001 -0.026 mg/kg. The recoveries of Method I
      for the spiked standards at concentration of 0.25 mg/kg were 72% - 113% with the
      relative standard deviations (RSDs) of 3.4% - 12.1%. The recoveries of Method II
      were 51% - 127%, among which the recoveries for 94% pesticides were between 70%
      and 120% with the RSDs of 3.2% - 13.8%.

PMID- 18724663
TI  - [Analysis of volatile components in Qingshanlvshui tea using solid-phase
      microextraction/accelerated solvent extraction-gas chromatography-mass
      spectrometry].
AB  - The volatile components of Qingshanlvshui Tea were extracted using solid phase
      micro-extraction (SPME) and accelerated solvent extraction (ASE), and then were
      identified by gas chromatography-mass spectrometry (GC-MS). It showed that ninety
      one compounds were identified, including forty-nine by SPME, fifty-six by ASE,
      and fourteen by both of them. The main constituents were beta-myrcene, 3,5,5
      trimethyl-1,5-heptadiene, L-limonene, alpha-ocimene, beta-ocimene, beta-pinene, 2
      methylbenzaldehyde, 5-(hydroxymethyl)-2-furfural. Both SPME and ASE have their
      advantages. SPME is excellent at simplicity, rapidity, solvent-free, high
      enrichment, low detection limit, environment friendly etc. ASE has
      characteristics of time and solvent saving, automation, simplicity, as well as
      high efficiency.

PMID- 18724664
TI  - [Application of single drop microextraction in the determination of phthalate
      esters and parabens in drugs by gas chromatography-mass spectrometry].
AB  - Single drop microextraction (SDME) was used for the determination of phthalate
      esters and parabens in drugs by gas chromatography-ion trap mass spectrometry (GC
      IT/MS). The effects of the nature of extraction solvents, microdrop volume, the
      depth of microdrop in sample solution, extraction time and stirring rate on the
      extraction efficiency were investigated separately. The optimal SDME conditions,
      1.5 microL of toluene, 0.8 cm of the depth of microdrop, 1 000 r/min of stirring
      rate and 20 mm of extraction time, were obtained and used for the analysis of
      methylparaben (MP), ethylparaben (EP), propylparaben (PP), iso-propylparaben
      (IPP), butylparaben (BP), dimethyl phthalate (DMP), diethyl phthalate (DEP) and
      dibutyl phthalate (DBP) in drugs. The results showed that the working curves for
      8 phthalate esters and parabens were linear in the range of 0.032 - 80 mg/L by GC
      MS on selective ion storage mode. The limits of detection (LOD) were between 0.6
      microg/L and 1.28 mg/L, the overall recoveries were 95.85% - 148.85% with the
      relative standard deviations of 3.9% - 14.9%.

PMID- 18724665
TI  - [Determination of monoethylglycinexylidide concentration in serum using solid
      phase extraction and capillary gas chromatography-mass spectrometry].
AB  - A novel method for the determination of monoethylglycinexylidide (MEGX)
      (lidocaine metabolin) in serum using solid phase extraction (SPE) and capillary
      gas chromatography-mass spectrometry (GC-MS) was established. The serum sample
      was extracted with a CN-SPE column. An HP-5MS capillary column (15 m x 0.25 mm x
      0.1 microm) was used. The initial temperature of the column was set at 100
      degrees C, held for 1 min, then raised to 200 degrees C at 40 degrees C/min, and
      held at 200 degrees C for 0.5 min. The sample size was 2 microL, and the split
      ratio was set at 1 : 1. The carrier gas was high purity helium with a flow rate
      of 1.0 mL/min. The monitoring ions for the determination were m/z 58 for MEGX and
      m/z 86 for procaine (internal standard). The calibration curve of MEGX had good
      linear relationship in the range of 1.562 - 25 ng/mL ( r = 0.998 1). The limit of
      detection was 0.5 ng/mL. The extraction recovery ranged from 80.1% to 85.7%. The
      method advanced the quantitative analysis of MEGX in serum by combining rapid and
      efficient SPE with specific and sensitive quantitation by GC-MS.

PMID- 18724666
TI  - [Rapid determination of alkaloids in tobacco using gas chromatography-mass
      spectrometry with full scan-selected ion monitoring mode].
AB  - Simultaneous full scan-selected ion monitoring mode (Scan-SIM) is a new
      improvement method of data acquisition of gas chromatography-mass spectrometry
      (GC-MS). A method of determing alkaloids in tobacco was established by GC-MS with
      Scan-SIM. Nicotine, nornicotine, anabasine and anatabine were determined with
      scan mode, and myosmine, nicotyrine, 2,3'-bipyridyl and cotinine were determined
      with SIM mode. The average recoveries of alkaloids ranged from 94.8% to 98.8%,
      and the relative standard deviations were less than 6.0% (n = 5). Therefore, it
      is a simple, rapid, accurate method. Tobacco samples picked in different years
      were determined using this method, and the results were satisfactory.

PMID- 18724667
TI  - [Determination of flumioxazin residue in foods using gas chromatography-mass
      spectrometry].
AB  - A method for the determination of flumioxazin residue in foods by gas
      chromatography-mass spectrometry (GC-MS) has been developed. The food sample was
      extracted with acetonitrile or ethyl acetate, concentrated in a rotary
      evaporator, then dissolved in acetonitrile-methyl benzene (3 : 1, v/v) and
      purified with an NH2-solid phase extraction (SPE) column. The final extract was
      analyzed by gas chromatography-mass spectrometry with selected ion monitoring
      mode (GC-MS-SIM). External standard method was used for the quantification. The
      mean recoveries of flumioxazin spiked in foods were 79.4% - 101%, and the
      relative standard deviations were 0.242% -7.15% (n = 10). The detection limit for
      each was 0.01 mg/kg. This method has high sensitivity, veracity and is suitable
      for the determination of pesticide residues in foods.

PMID- 18724668
TI  - [Determination of ifenprodil in human plasma using liquid chromatography with
      electrospray tandem mass spectrometry].
AB  - A method for the determination of ifenprodil levels in human plasma was
      established. Ifenprodil and the internal standard (IS), ketoconazole, were
      extracted from the plasma with ethyl acetate using liquid-liquid extraction. The
      extracts were separated by high performance liquid chromatography (HPLC) using
      methanol-6 mmol/L ammonium acetate (pH value was adjusted to 7.40) (90 : 10, v/v)
      as the mobile phase, and were then detected using mass spectrometry (MS).
      Electrospray source was applied and operated in positive ion mode. Selected
      reaction monitoring (SRM) mode with the transition of m/z 326.1 --> 308.2 was
      used to quantify ifenprodil, and m/z 531.0 --> 82.1 for IS. The excellent
      sensitivity and selectivity of the HPLC-MS/MS method allowed quantitation and
      identification of ifenprodil at low levels with a run time of 6.0 min. The assay
      was linear over the range from 0.25 to 50 microg/L. The intra-day and inter-day
      precisions measured as relative standard deviations (RSDs) were less than 2.7%
      and less than 6.5%, respectively. The average recoveries varied between 101.3%
      and 105.0%, and the detection limit was 0.08 microg/L. Due to its simplicity and
      accuracy, the established method is suitable for the application in a
      pharmaceutical study of the intervenous drop infusion of ifenprodil tartrate.

PMID- 18724669
TI  - [Determination of simvastatin in human plasma using ultra-performance liquid
      chromatography-tandem mass spectrometry].
AB  - A rapid, sensitive and specific method has been developed for the determination
      of simvastatin in human plasma with ultra-performance liquid chromatography
      tandem mass spectrometry. Simvastatin and the internal standard (lovastatin) were
      extracted from human plasma with diethyl ether-n-hexane-isopropanol (80: 20 : 3,
      v/v/v), then separated on a Waters ACQUITY UPLC BEH C18 column (50 mm x 2.1 mm,
      1.7 microm) with isocratic elution at a flow rate of 0.25 mL/min. The mobile
      phase was composed of 85% acetonitrile and 15% water (containing 10 mmol/L
      ammonium acetate). Electrospray ionization (ESI) source was applied and operated
      in positive ion mode. Multiple reaction monitoring (MRM) mode with the
      transitions of m/z 419. 2 --> m/z 199.0 and m/z 405. 0 --> m/z 199.0 was used to
      quantify simvastatin and the internal standard, respectively. The linear
      calibration curve was obtained in the concentration range of 0.051 - 20.4 ng/mL.
      The lower limit of quantification was 0.051 ng/mL. The inter-day and intra-day
      precision (relative standard deviation) were less than 10%, and the accuracy
      (relative error) was within -2.7% - 0% calculated from quality control samples.
      The mean extraction recovery of simvastatin was 91.6%. The method was proved to
      be selective, sensitive, rapid and suitable for the pharmacokinetic study of
      simvastatin.

PMID- 18724670
TI  - [Fast separation and preparation of proteomics samples of human serum using high
      performance hydrophobic interaction chromatographic cake].
AB  - A method for the fast separation of human serum and enrichment of low abundance
      proteins was developed using offline 2D liquid chromatography (2D-LC) consisted
      of chromatographic cake (10 mm x 20 mm i. d.) and reversed-phase liquid
      chromatography (RPLC). The protein after separation and enrichment was detected
      using matrix assisted laser desorption/ ionization time of flight mass
      spectrometry (MALDI-TOF MS). This method was validated by four standard proteins
      at very low concentration. It was found that the detection limits were 1
      pmol/microL for the enriched cytochrome-c and myoglobin, and 0.1 pmol/microL for
      enriched lysozyme and insulin. This method has been applied to the proteomic
      research of human serum, and it was found that the signal intensity and the
      number of detected proteins/peptides in MALDI-TOF MS increased with the increase
      of the loading sample volume of the human serum on chromatographic cake. A total
      of 285 fractions (M(r) < 15 000) were found when 1.0 mL serum sample was loaded
      on the chromatographic cake. In addition, cytochrome-c in low abundance was also
      separated and enriched successfully when 1 microg cytochrome-c was added into 0.5
      mL original serum. The results showed that 2D-LC consisting of the
      chromatographic cake and RPLC was successfully applied to not only the fast
      separation and preparation of human serum sample with large loading volume in one
      cycle of analysis, but also the efficient isolation and enrichment of the lower
      abundance proteins/peptides in human serum. Moreover, it successfully increased
      the detection efficiency of the low abundance proteins/peptides in human serum
      with MALDI-TOF MS.

PMID- 18724671
TI  - [Analysis of chlorogenic acids in Helianthus tuberosus Linn leaves using high
      performance liquid chromatography-mass spectrometry].
AB  - To identify chlorogenic acids in Helianthus tuberosus Linn leaves, a method of
      high performance liquid chromatography-ultraviolet-mass spectrometry (HPLC-UV-MS)
      was developed. HPLC analysis was performed on an Inertsil ODS-3 column (250 mm x
      4.6 mm, 5 microm). The mobile phase consisted of 1% acetic acid (A) and methanol
      (B). A gradient program was adopted as follows: 0 - 10 min, 20% B to 35% B; 10 -
      25 min, 35% B to 50% B; 25 - 35 min, 50% B to 80% B. The flow rate was set at 1.0
      mL/min and the column temperature was 35 degrees C. HPLC chromatogram was
      extracted at 327 nm. The mass spectrometer used was a TSQ triple quadrupole MS
      equipped with an electrospray ionization (ESI) interface. Initially, the mass
      spectrometer was programmed to perform full scan ranging from m/z 250 - 1 200.
      For MS/MS, negative ion monitoring mode was used and the collision energy was set
      at 10 - 45 eV. By analyzing UV characteristics and MS fragmentation patterns, 7
      chlorogenic acids were assigned to be three categories, i. e., three
      caffeoylquinic acids, one feruloylquinic acid and three dicaffeoylquinic acids.
      As the results of the method development efforts, an effective and fast method
      for the qualitative identification of the chlorogenic acids in Helianthus
      tuberosus Linn leaves was established.

PMID- 18724672
TI  - [Determination of melamine residue in feeds by ultra performance liquid
      chromatography coupled with electrospray tandem mass spectrometry].
AB  - A method for fast determination melamine residue in feeds was established. An
      ultra performance liquid chromatography coupled with electrospray ionization
      quadrupole tandem mass spectrometry (UPLC-ESI-MS/MS) was used. The residue was
      quantified with multiple reaction monitoring (MRM) mode. The method was validated
      and good results were obtained with respect to precision, repeatability and
      spiked recovery. The limit of detection was 10 microg/kg for melamine, and the
      linear range was from 10 to 5 000 1g/kg. The average recoveries were between 83%
      and 94% in the spiked range of 10 - 100 microg/kg, and the relative standard
      deviations (RSDs) were between 4.2% and 6.5%. The method has good repeatability
      and high sensitivity, and can be applied for the determination of melamine
      residue in feeds.

PMID- 18724673
TI  - [Isolation and identification of lipopeptides produced by Bacillus subtilis using
      high performance liquid chromatography and electrospray ionization mass
      spectrometry].
AB  - Bacillus subtilis JA produces a broad spectrum of bioactive lipopeptides with
      great potential applications in agriculture and industry. Crude lipopeptides were
      extracted with 100% methanol from the precipitate which was obtained by adding 6
      mol/L HCl to the cell-free culture broth. The crude extract was separated on a
      Diamonsil C18 column (5 microm, 250 mm x 4.6 mm) in reversed-phase high
      performance liquid chromatography (HPLC) system to separate the lipopeptide
      homologues. Five peaks were eluted from HPLC. Electrospray ionization mass
      spectrometry (ESI-MS) was used to analyze each HPLC fraction. The results showed
      three series of ion peaks. According to the values of m/z, the three series of
      ions were classified into surfactin, iturin and fengycin homologues, which were
      well-known biosurfactants produced by B. subtilis strains. The major ions were
      structurally characterized using tandem mass spectrometry. This study suggested a
      reasonable method for the isolation and identification of lipopeptides produced
      by B. subtilis strains.

PMID- 18724674
TI  - [Simultaneous determination of sulfonamides and fluoroquinolones residues in
      chicken by high performance liquid chromatography-electrospray tandem mass
      spectrometry].
AB  - A method was developed for the simultaneous determination of 10 residual
      antibiotics--three sulfonamides (sulfadiazine, sulfamethazine and
      sulfamethoxydiazine) and seven fluoroquinolones (enoxacin, norfloxacin,
      enrofloxacin, fleroxacin, levofloxacin, lomefloxacin and ciprofloxacin) in
      chicken by high performance liquid chromatography-electrospray tandem mass
      spectrometry (HPLC-ESI-MS2). The sample was extracted with 2% acetic acid
      acetonitrile for three times and defatted with n-hexane, then purified by an ENVI
      18 solid-phase extraction column. After evaporation, the residue was dissolved in
      the mobile phase of 1 mL. The HPLC separation was performed with a gradient
      elution program of acetonitrile and water (containing 0.05% formic acid) as the
      mobile phase. The identification and quantification were done with mass
      spectrometry. MS2 fragmentation pathways of the ten antibiotics were also
      analyzed. Good linearities were observed in the range from 0.02 to 2.0 mg/L with
      correlation coefficients above 0.998 8. The limits of detection (LOD) were 1.10 
      6.85 microg/kg and the limits of quantification (LOQ) were 3.68 -22.85 microg/kg.
      The average recoveries of 10 antibiotics ranged from 68.9% to 102.6% with
      relative standard deviations below 8.6% (n = 3). The experimental results show
      that this method is of high sensitivity, good reproducibility, better
      determination capacity and shorter analysis time. The method can be used for the
      multi-residue analysis of sulfonamides and fluoroquinolones in animal foods.

PMID- 18724675
TI  - [Determination of Sudan Red dyes in eggs using liquid chromatography-tandem mass
      spectrometry and matrix solid-phase dispersion technique].
AB  - A new method was established for determining Sudan Red I - IV dyes in eggs using
      liquid chromatography-tandem mass spectrometry (LC-MS/MS). The target analytes in
      eggs such as hen eggs, duck eggs and preserved eggs, were extracted by solid
      phase dispersion technique with a mixture of chloroform-acetonitrile (9: 1, v/v).
      The chromatographic separation was achieved on a ZORBAX SB-C18 column. The
      identification and quantification were performed using MS/MS with multiple
      reaction monitoring (MRM) and electrospray ionizatio in positive mode. The
      linearity ranges of Sudan Red I - IV dyes were 0.5 - 100 ng/g, 5.0 - 100 ng/g,
      1.0 - 100 ng/g and 2.0 - 100 ng/g, respectively, and all linear correlation
      coefficient were higher than 0.99. The recoveries of Sudan Red dyes in eggs were
      between 87.3% and 113% with the relative standard deviations less than 9.1%. The
      detection limits of this method were 0.1 microg/kg for Sudan Red I, 2.0 microg/kg
      for Sudan Red II , 0.2 microg/kg for Sudan Red III and 0.4 microg/kg for Sudan
      Red IV, which could meet the monitoring requirements of the Suda Red dyes both
      abroad and home.

PMID- 18724676
TI  - Simultaneous determination of gatifloxacin and ambroxol hydrochloride from tablet
      dosage form using reversed-phase high performance liquid chromatography.
AB  - A reversed-phase high performance liquid chromatography (HPLC) method was
      developed, validated, and used for the quantitative determination of gatifloxacin
      (GA) and ambroxol hydrochloride (AM), from its tablet dosage form.
      Chromatographic separation was performed on a HiQ Sil C18 column (250 mm x 4.6
      mm, 5 microm), with a mobile phase comprising of a mixture of 0.01 mol/L
      potassium dihydrogen orthophosphate buffer and acetonitrile (70 : 30, v/v), and
      pH adjusted to 3 with orthophosphoric acid, at a flow rate of 1 mL/min, with
      detection at 247 nm. Separation was completed in less than 10 min. As per
      International Conference on Harmonisation (ICH) guidelines the method was
      validated for linearity, accuracy, precision, limit of quantitation, limit of
      detection, and robustness. Linearity of GA was found to be in the range of 10 -60
      microg/mL and that for AM was found to be 5 - 30 microg/mL. The correlation
      coefficients were 0.999 6 and 0.999 3 for GA and AM respectively. The results of
      the tablet analysis (n = 5) were found to be 99.94% with +/- 0.25% standard
      deviation (SD) and 99.98% with +/- 0.36% SD for GA and AM respectively. Percent
      recovery of GA was found to be 99.92% - 100.02% and that of AM was 99.86% -
      100.16%. The assay experiment shows that the method is free from interference of
      excipients. This demonstrates that the developed HPLC method is simple, linear,
      precise, and accurate, and can be conveniently adopted for the routine quality
      control analysis of the tablet.

PMID- 18724677
TI  - [Preparation of asiaticoside and madecassoside from the extract of Centella
      asiatica (L.) Urb using preparative high performance liquid chromatography].
AB  - A high performance liquid chromatographic (HPLC) method was successfully used to
      separate asiaticoside and madecassoside from the extract of Centella asiatica
      (L.) Urb. The raw material containing 20% asiaticoside and 45% madecassoside was
      dissolved in methanol and used for the preparation of the pure compounds. The
      flow rate of the mobile phase, injection volume and detection wavelength were
      optimized. The optimum operation parameters were then selected as follows: a C18
      column (50 mm x 200 mm, 5 microm) with methanol-water (60 : 40, v/v) as the
      mobile phase at a flow rate of 100 mL/min, the detection wavelength of 220 nm,
      and the injection volume of 1.5 mL at the concentration of 40 mg/mL. Asiaticoside
      and madecassoside the can be obtained in a 20 min runtime, and the purities of
      the products were detected by melting point, thin layer chromatography (TLC) and
      HPLC method. The results showed that the purities of products were above 98%. The
      effective and rapid method has been successfully applied and to the preparation
      of asiaticoside and madecassoside from Centella asiatica (L. ) Urb.

PMID- 18724678
TI  - [Preparation of three capsaicinoid components using preparative high performance
      liquid chromatography].
AB  - A method was established for the isolation of three capsaicinoid components from
      capsaicinoids using preparative high performance liquid chromatography (Pre
      HPLC). A preparative PRC-ODS column (250 mm x 21.5 mm, 13 microm) was used in the
      preparation process. By isocratic elution with methanol-water (70 : 30, v/v) as
      the mobile phase at a flow rate of 15 mL/min followed by concentration, three
      capsaicinoid components were obtained from 80% capsaicinoids, and subsequently
      identified by 1H NMR (nuclear magnetic resonance) and EI-MS (electron impact-mass
      spectrometry) as nordihydrocapsaicin, capsaicin and dihydrocapsaicin, and the
      purities of the three components analyzed by HPLC were 98.12%, 99.93% and 100.7%
      with yields of 60.1%, 58.9% and 72.3%, respectively.

PMID- 18724679
TI  - [Relationship of resistance to diseases and water-soluble amino acids in Konjac
      leaves].
AB  - Reversed-phase high performance liquid chromatography was used to analyze water
      soluble amino acids in the normal Amorphophallus Konjac, Amorphophallus albus,
      Amorphophallus bulbifer, and the soft rot Amorphophallus Konjac, to determine the
      relationship of the different soft-rot resistant Konjac varieties and the
      proportion and content of the multiple water-soluble amino acids. The results
      showed that there are remarkable differences in the content and proportion of
      water-soluble amino acids in different resistant varieties and the same variety
      of normal and diseased leaves of Amorphophallus. In this study, the bank of
      fingerprint 15 chromatogram was established and can be used to analyze the
      related characteristic peaks and the resistance of Amorphophallus.

PMID- 18724680
TI  - [Establishment and application of a two-dimensional liquid chromatographic system
      (NPLC x RPLC)].
AB  - A two-dimensional liquid chromatographic system (NPLC x RPLC) has been developed.
      Normal phase liquid chromatography (NPLC) with a Hypersil SiO2 column (50 mm x
      4.6 mm) was used as the first dimension, and reversed-phase liquid chromatography
      (RPLC) with a Kromasil C18 column (250 mm x 4.6 mm) was used as the second
      dimension. The interface was a ten-port, two-position valve with two storage
      loops. As to improve the compatibility of the two dimensional mobile phase and be
      good for adjusting the selectivity of separation, 1,4-dioxane was used in the
      mobile phase of the first dimension, and isopropyl alcohol was used in the mobile
      phase of the second dimension based on the characters of the organic solvents. By
      raising the temperature of the second dimension, the incompatibility of the two
      dimensional mobile phases was avoided. A Chinese potent medicine, Zhengtian Wan,
      was analyzed by this system. The total peak capacity reached 1 220.

PMID- 18724681
TI  - [Preparation of affinity chromatographic packings by immobilization of Cibacron
      Blue F3GA based on monodispersed non-porous hydrophilic poly (glycidylmethacry-co
      ethylenedimethacrylate) particles and their application].
AB  - An affinity chromatographic packing was prepared by the immobilization of
      Cibacron Blue F3GA as dye ligands on the base of monodispersed, 3.0 microm non
      porous hydrophilic poly glycidylmethacry-co-ethylenedimethacrylate) particles.
      The effects of the ionic strength, organic solvent in the mobile phase and flow
      rate on protein retention were investigated on the chromatographic stationary
      phase. The apparent dissociation constant between the immobilized Cibacron Blue
      F3 GA and lysozyme (Lys) was 5.26 x 10(-5) mol/L which was evaluated by frontal
      chromatography. Purifications of Lys from egg white and bovine serum albumin
      (BSA) from blood were performed on the dye-ligand chromatographic column,
      separately, and the purities of the obtained fractions were determined by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The purities of the
      purified Lys and BSA were determined to be 5% and 92%, respectively.

PMID- 18724682
TI  - [Separation and purification of porcine hemoglobin from porcine blood].
AB  - In order to perform the isolation and purification of porcine hemoglobin from
      porcine blood. A three-step method, utilizing ultrafiltration, DEAE-Sepharose
      Fast Flow anion-exchange chromatography and Sephadex G-75 gel exclusion
      chromatography in sequence, for the separation and purification of porcine
      hemoglobin was developed. The obtained hemoglobin was analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), high-performance size
      exclusion chromatography and reversed-phase high performance liquid
      chromatography. Through the three-step purification process, the purity of the
      obtained hemoglobin was more than 99% with a concentration of 1.328 g/L.

PMID- 18724683
TI  - [Analysis of computational chemistry for the coordination character of Cu2+ and
      quercetin and kaempferol].
AB  - A model based on computational chemistry was established to simulate the
      coordination character of Cu2+ and flavone compounds. Grid program package in
      MVD2007 was used in calculating the simulation of the coordination effect between
      Cu2+ and two flavone compounds, kaempferol and quercetin, both of which have the
      lowest-energy conformation. Then the potential energy surface of interactional
      force field and relative binding energy were obtained. By comparing the relative
      binding energy of the two different compounds and analyzing the result of high
      performance liquid chromatographic (HPLC) method, it is indicated that the link
      between Cu2+ and kaempferol is stronger than that between Cu2+ and quercetin. A
      good correlation between the values of relative binding energies and the HPLC
      result suggests that the calculation method is reliable, and hence provides a
      theoretical basis for the separation in the area of coordination chemistry.

PMID- 18724684
TI  - [Simultaneous determination of canthaxanthin and astaxanthin in feedstuffs using
      solid phase extraction-reversed-phase high performance liquid chromatography].
AB  - A method was developed for the simultaneous determination of canthaxanthin and
      astaxanthin in feedstuffs using reversed-phase high performance liquid
      chromatography (RP-HPLC). The sample was extracted by acetonitrile, and cleaned
      up by an LC-NH2 column. An Agilent ZORBAX Eclipse XDB-C18 analytical column (150
      mm x 4.6 mm, 5 microm) was used and kept at 25 degrees C. Acetonitrile-methanol
      (95 : 5, v/v) was used as the mobile phase at a flow rate of 1.0 mL/min. The
      detection was performed by a diode array detector at 474 nm. The quantitive
      analysis of external standard calibration curves was used. The linear ranges of
      the method for canthaxanthin and astaxanthin were 1.0 - 30.0 mg/L (r = 0.999 0)
      and 1.0 - 20.0 mg/L (r = 0.999 1), respectively. The average recoveries were 90% 
      101% with the relative standard deviations of 0.62% - 3.68%. The detection
      limits were 0.84 and 0.60 mg/L for canthaxanthin and astaxanthin, respectively.
      The method is simple, precise, sensitive and reproductive. It can be used to
      determine the contents of canthaxanthin and astaxanthin in feedstuffs.

PMID- 18724685
TI  - [Determination of streptomycin residue in royal jelly by high performance liquid
      chromatography with post-column derivatization].
AB  - A reliable and sensitive method was introduced for the analysis of streptomycin
      in royal jelly. The method was based on a separation by a C8 analytical column
      with beta-naphthoquinone-4-sulfonate post-column derivatization and fluorescence
      detection. The clean-up of the extract was done by solid-phase extraction,
      firstly with an octadecyl cartridge and secondly with a cation-exchange
      cartridge. The linear range was 0.02 - 0.5 mg/L and the correlation coefficient
      was 0.995 8. The limits of detection (S/N = 3) and quantitation (S/N = 10) of
      streptomycin were 0.005 mg/kg and 0.01 mg/kg, respectively. The recoveries ranged
      from 84.0% to 104.0% with the relative standard deviations not larger than 7.9%.
      The method reduced the possibility of the false positive, and it could meet the
      need of the current work.

PMID- 18724686
TI  - [Determination of triazolam in human urine by gas chromatograph-micro electron
      capture detector].
AB  - Triazolam is often abused in criminal activities. It is necessary to develop a
      simple, fast and sensitive method for determining triazolam in human urine. After
      the triazolam in urine was extracted with ether at pH 9, the analysis was
      performed on an HP-5 capillary column with gas chromatograph-micro electron
      capture detector (GC-muECD). The calibration curve of triazolam showed good
      linearity in the range of 0.2 - 50 ng/mL with the correlation coefficient of
      0.999 5. The inter-day relative standard deviation (RSD) and intra-day RSD were
      4.17% and 5.31%, respectively. The average recovery was 93.9%. This simple,
      sensitive and accurate method can be easily implemented for monitoring triazolam
      in urine.

PMID- 18724687
TI  - Adventitious roots and secondary metabolism.
AB  - Plants are a rich source of valuable secondary metabolites and in the recent
      years plant cell, tissue and organ cultures have been developed as an important
      alternative sources for the production of these compounds. Adventitious roots
      have been successfully induced in many plant species and cultured for the
      production of high value secondary metabolites of pharmaceutical, nutraceutical
      and industrial importance. Adoption of elicitation methods have shown improved
      synthesis of secondary metabolites in adventitious root cultures. Development of
      large-scale culture methods using bioreactors has opened up feasibilities of
      production of secondary metabolites at the industrial levels. In the present
      review we summarize the progress made in recent past in the area of adventitious
      root cultures for the production of secondary metabolites.

PMID- 18724688
TI  - [Regulatory genes of geldanamycin biosynthesis].
AB  - Two LAL family regulatory genes, gdmRI and gdmRII, were identified in the
      geldanamycin biosynthetic gene cluster of Streptomyces hygroscopicus 17997.
      Disruption of the two regulatory genes resulted in absolute elimination of
      geldanamycin biosynthesis. The complementation experiments using a single wild
      type gene could restore geldanamycin production. These results indicated that
      both gdmRI and gdmRII were positive regulatory genes of the geldanamycin
      biosynthesis.

PMID- 18724689
TI  - [Molecular cloning, recombinant expression and characterization of lysozyme from
      Chinese shrimp Fenneropenaeus chinensis].
AB  - Lysozyme hydrolyses bacterial cell walls and acts as a nonspecific innate
      immunity molecule against the invasion of bacterial pathogens. We cloned the cDNA
      of lysozyme from Fenneropenaeus chinensis and named Fc-lysozyme (FcLyz in short).
      The full length of the gene was of 709 bp, and the open reading frame (477 bp)
      encoded 158 amino acids. The predicted protein had a signal peptide (-1--18
      residue) and molecular weight of the mature protein (residue 1-140) was of 16.2
      kD. A Lyz 1 domain (residue 1-130) in the lysozyme was found by SMART analysis.
      The results of semiquantity RT-PCR showed that FcLyz was constitutively expressed
      in tested tissues in a low level in normal shrimp, and up-regulated in hemocytes,
      heart, hepatopancreas and gill of bacterial challenged shrimp. The DNA fragment
      of mature Fc-Lys was subcloned to pET-30a (+) expression vector, the recombinant
      plasmid was transformed into Escherichia coli BL21 (DE3) and then induced by
      isopropylthio-beta-D-galactoside (IPTG). The antibacterial activity of the
      purified recombinant FcLys was analyzed and minimal inhibitory concentration
      (MIC) was assayed. The recombinant protein showed high antibacterial activity
      against some Gram-positive bacteria, and MIC reached 3.43 micromol/L, and
      relatively low activity against Gram-negative bacteria. All together, the Fc-Lys
      was regulated by pathogen infection and had antibacterial activity. This
      suggested that the FcLyz may be one of the important molecules against pathogens
      in innate immunity of the shrimp.

PMID- 18724690
TI  - [Screening of T7 phage-display cDNA library from liver of Microtus fortis with
      extracts of schistosomulum and characterization of the positive clones].
AB  - Microtus fortis is naturally resisitent to Schistosoma japonicum. In order to
      find schistosome-resistence-related genes of Microtus fortis, a T7 phage-display
      cDNA library from liver of Microtus fortis was screened with the soluble lysate
      of schistosomula. The specific phages were enriched 375-fold after 3 rounds of
      biopanning. Ninety-two positive clones picked at random were sequenced and 19
      ESTs including 6 unreported genes were obtained. Compared with the negative phage
      clone control, five positive clones, No.4 (GenBank Accession No.: EW968294),
      No.13 (GenBank Accession No.: EW968303), No.14 (GenBank Accession No.: EW968304),
      No.15 (GenBank Accession No.: EW968305) and No.18 (GenBank Accession No.:
      EW968308) could induce significantly higher schistosomula mortality rate when co
      cultivated with schistosomula. According to the function analysis and the
      shistosomula-killing effect in vitro, the genes encoding CASP8 and FADD-like
      apoptosis regulator isoform protein, alpha-2-HS-glycoprotein, M4 protein, R3H
      domain (binds single-stranded nucleic acids) isoform 2 and 3 previously
      unreported proteins (No.14, No.15 and No.18) obtained here, were schistosomiasis
      resistence-related genes of Microtus fortis.

PMID- 18724692
TI  - [Sequential expression of Wnt/beta-catenin signal pathway related genes and
      adipocyte transcription factors during porcine adipose tissue development].
AB  - To evaluate the influence of Wnt/beta-catenin signal pathway on the porcine
      adipose tissue development and explore the mechanism, we detected the mRNA
      expression of Wnt/beta-catenin signal pathway related genes: beta-catenin,
      GSK3beta, Fzl and adipogenic transcription factors: PPARy, C/EBPalpha and early
      differentiation marker gene LPL with semi-quantitative (SQ) RT-PCR method.
      Immunohistochemical method (IHC) was applied to qualitatively measure the
      sequential expression of beta-catenin protein. The results of SQ RT-PCR showed
      that beta-catenin highly expressed at the first day after birth, then decreased
      to a low plateau after 60 days, the expression of GSK3beta and Fzl also decreased
      with the development process of the porcine adipose tissue development. However,
      the sequential expression of PPARgamma, C/EBPalpha, LPL appeared to be an
      opposite manner and kept at a high level after 60 days. The result of IHC showed
      that the expression of beta-catenin protein was strong in nucleus and cytoplasm
      at the first day after birth, then tended to decline with the process of adipose
      tissue development and could be only found in cytoplasm after 30-day old. These
      results suggest that beta-catenin plays an important role in the undifferentiated
      state maintenance of preadipocytes and the inhibition of porcine adipose tissue
      development, the mechanism maybe due to its regulation function on the adipogenic
      transcription factors PPARy, C/EBPalpha and early differentiation marker gene
      LPL.

PMID- 18724691
TI  - [Construction of recombinant retroviral vector carrying Lab gene of foot-and
      mouth disease virus and its expression in bovine kidney (MDBK) cells].
AB  - In this study, foot-and-mouth disease virus (FMDV) strain OA/58 RNAs were used as
      templates for RT-PCR. By the molecular cloning, the Lab gene encoding leader
      protease called Lpro were cloned in retroviral vector pBPSTR1 to obtain
      reconstruction retroviral vector termed pBPSTR1-Lab. At different concentrations
      of puromycin and tetracycline respectively in the cell culture mediums, the
      growth of bovine kidney cells (MDBK) showed that the optimal puromycin resistant
      selection concentration was 3 microg/mL and tetracycline regulatory concentration
      was 1 microg/mL. Pseudotyped retroviral virus particles were produced by
      transiently co-tansfecting GP2-293 cells with a retroviral vector DNA and VSV-G
      plasmid. Then MDBK cells were infected by pseudotyped retroviral virus and were
      continually seeded in the medium at the optimal tetracycline regulatory
      concentration and puromycin selection concentration for 12 days to obtain
      puromycin resistant colonies whose genomes contained the Lab gene. After
      tetracycline removal, synthesis of Lpro induced severe morphological changes in
      the puromycin resistant MDBK cells. PCR and Western blotting proved that a stable
      MDBK cell line inducibly expressing the Lab gene under the control of
      tetracycline was obtained. The experiment might provide a basis for studying that
      Lpro of FMDV plays an important role in MDBK cell pathogenesis.

PMID- 18724693
TI  - [GAPDH activity and immunogenicity of Staphylococcus aureus recombinant GapC
      protein].
AB  - In order to characterize the Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      activity, immunogenicity and immunoprotection of the Staphylococcus aureus (S.
      aureus) surface protein GapC, gapC gene of S. aureus was amplified from strain
      BMSA/855/23-1 by PCR, and was inserted into pQE-30 vector subsequently. The
      recombinant plasmid, designated as pQE/gapC, was transformed into E. coli strain
      M15 (pREP4). The recombinant GapC fusion proein was successfully expressed in E.
      coli M15 induced with IPTG and its GAPDH activity was confirmed by GAPDH activity
      assay. Then, the recombinant GapC protein, inactivated S. aureus whole cell and
      placebo (PBS) were administrated to healthy rabbits respectively. The IgG
      antibody titers, concentration of IFN-gamma and IL-4 cytokines in immunized
      rabbit sera were measured with Enzyme-Linked Immunosorbnent Assay (ELISA).
      Finally, immunized rabbits were challenged with S. aureus strain Wood46 to
      evaluate the immunoprotection. The IgG antibody titers against GapC and whole
      cell in rabbit sera reached their peaks at day 28 after boost immunization
      (1:64,000). The concentration of IL-4 and IFN-gamma in GapC groups rabbit sera
      increased significantly (P<0.05) at day 14 after boost immunization, while the
      concentration of those in whole cell group did not increase (P>0.05) compared
      with the placebo group. 4 rabbits in 5 of the protein immunized group were
      protected against challenge with 1 x 10(8) CFU S. aureus. The results above
      indicate that the expressed recombinant GapC protein have high GAPDH activity and
      immunogenicity, can also protect against S. aureus challenge to some extent. S.
      aureus GapC protein could be an attractive target for further genetic engineering
      vaccine.

PMID- 18724694
TI  - [Phage resistance of Corynebacterium crenatum conferred by the restriction and
      modification system cglI].
AB  - In order to prevent phage contamination in amino acid fermentation, we introduced
      the restriction and modification system cglI gene complex into Corynebacterium
      crenatum and studied their phage-resistance. The cglI gene complex was amplified
      from Corynebacterium glutamicum by PCR and constructed into pJL23 vector. The
      recombinant strains were obtained by transformation of the recombinant plasmid
      pJL23-cglI into C. crenatum. Results showed that the recombinant strains
      possessed strong phage-resistance activity and broad phage-resistance spectrum,
      demonstrating the feasibility of using cglI gene complex for construction of
      phage-resistance recombinant C. crenatum strains and presenting a powerful way to
      solve the problem of phage contamination in amino acid fermentation industry.

PMID- 18724695
TI  - [Construction and biological characteristic for the recombinant modified vaccinia
      virus ankara co-expressing modified GP5 and M protein of porcine reproductive and
      respiratory syndrome virus].
AB  - Modified ORF5 (MORF5) and ORF6 gene of PRRSV were cloned into two multiple
      cloning sites of MVA transfer vector pLR-gpt to construct the recombinant plasmid
      pLR-MORF5/ORF6. Homologous recombination between pLR-MORF5/ORF6 and the wtMVA on
      BHK-21 cell line was mediated with liposome by infecting the cell with 0.01 MOI
      wtMVA two hours before transfecting the recombinant plasmid into the cell. When
      the cytopathic effect (CPE) was obvious, virus was collected from the cell plate
      and the recombinant virus was selected with drug selecting medium (2% MXHAT).
      After 12 cycles of selection, rMVA with a selection marker Eco gpt was obtained
      and named as rMVAgpt-MGP5/M. By infecting BHK-Cre expressing Cre recombinant
      enzyme, the Eco gpt marker in rMVAgpt-MGP5/M was deleted and this rMVA was named
      as rMVA-MGP5/M. The insertion of MORF5 and ORF6 into the MVA genome was confirmed
      with PCR analysis and the expression of MGP5 and M protein was identified with
      Western blot and IFA. Through biological study on the recombinant MVA, no obvious
      difference was observed between rMVA-MGP5/M and the wtMVA regarding to the CPE
      and growth curve. The recombinant MVA constructed in this study could coexpress
      the modified GP5 and M protein and the expressed product had good
      immunocompetence. Furthermore, the insertion of the MORF5 and ORF6 into MVA
      genome had no obvious effect on the replication and biological characteristics of
      this virus.

PMID- 18724696
TI  - [Construction of adenoviral vector encoding soluble human sTNFRI-IgGFc cDNA and
      its expression in human airway smooth muscle cells (HASMCs)].
AB  - Tumour necrosis factor (TNF-a) is a pro-inflammatory cytokine that has been
      implicated in many aspects of the airway pathology in asthma, and which has
      recently been highlighted as potentially important in refractory asthma. To study
      the feasibility of local treatment of asthma with recombinant adenovirus vector
      carrying soluble extra-cellular region of TNF receptor I-IgGFc (sTNFRI-IgGFc)
      fusion protein, The sTNFRI-IgGFc gene was subcloned into the adenovirus shuttle
      plasmid pDC316, the products were co-transfected into HEK293 cell line with
      helper plasmid pBHGloxDeltaE1,3Cre. The recombinant adenovirus (Ad-sTNFRI-IgGFc)
      was produced by homologous recombination of above 2 plasmids in HEK293 cells.
      After identification with PCR, Ad-sTNFRI-IgGFc was amplified and purified, its
      titer was measured by TCID50 assay. The transcription and expression of sTNFRI
      IgGFc gene in transfected human airway smooth muscle cells (HASMCs) was detected
      by RT-PCR, ELISA and immunological histochemistry. The anti-TNF activity assay of
      transfected HASMCs culture supernatant was measured by MTT. Ad-sTNFRI-IgGFc was
      successfully constructed with the titer of 3x10(10) TCID50/mL. Ad-sTNFRI-IgGFc
      can transfect HASMC with high efficacy. The transcription of sTNFRI-IgGFc mRNA
      and the expression of protein were confirmed in the transfected HASMCs. Moreover,
      the product in 100 microL expression supernatant could completely antagonize the
      cytolytic effect of 2ng TNFa on L929 cells, even at 1/64 dilution. This study
      forms the basement of the experiment study on local treatment of asthma with
      adenovirus expressing sTNFRI-IgGFc.

PMID- 18724697
TI  - [Characterization of murine leukemia virus recombinants bearing PRRSV GP5
      glycoproteins].
AB  - The highly virulent PRRSV isolate strain HN-1/06 was cultivated on Marc-145. To
      study the viral entry mechanisms, the GP5 gene of PRRSV isolate was amplified by
      RT-PCR and cloned into pcDNA3.0 to generate the expressing plasmid pcDNA-GP5.
      pcDNA-GP5 was transfected into 293T by the calcium phosphate precipitation
      method. Analysis of flow cytometry confirmed that the GP5 proteins were expressed
      in surface of the 293T cells. Then 293T cells were transfected with pcDNA-GP5,
      pHIT60 and pHIT111 plasmids to generate pseudotyping virus. The pseudotyping
      virus supernatant was harvested 48 hours post-transfection and was detected by
      Western blotting and infection assay. Western blotting indicated that the GP5
      glycoproteins were incorporated into the retroviral pseudotyped virus. Infection
      assay showed that the pseudotyped virus infected 293T and Mark-145 cell. The
      pseudotyped virus could be used to further study infectious mechanism of PRRSV.

PMID- 18724698
TI  - [The application of a new-type bioreactor in the ex vivo expansion of
      hematopoietic stem/progenitor cells].
AB  - Based on the requirement of culture conditions for hematopoietic stem and
      progenitor cells (HSPCs) ex vive expansion, we developed a new-type bioreactor by
      combining superiorities of static and stirred culture models. Stem cell factor
      (SCF), thrombopoietin (TPO), FLT-3 ligand(Flt-3) were used as the cytokines
      cocktails. The effects of the static and cyclic culture on the expansion
      characteristics of CD34+ selected cells were compared in the new-type bioreactor.
      After 7 d cultures, the expansion of total cells in the static culture was 13.86
      +/- 4.26 fold, higher than that in the cyclic culture (7.23 +/- 2.67 fold). The
      analysis of the fold expansion and the proportion of CD34+ cells showed that
      there was no marked difference between the static culture and the cyclic culture.
      However, the fold expansion and the proportion of CD34+CD38- cells were higher in
      the cyclic culture than those in the static culture (3.90 +/- 0.85 versus 1.82 +/
      0.58), which reflected more primary CD34+CD38- cells were obtained in the cyclic
      culture. The above results demonstrated that both the static culture and the
      cyclic culture could be used in ex vive expansion of CD34+ cells with the new
      type bioreactor. In static culture hematopoietic stem cells differentiated into
      progenitor cells, whilst the cyclic culture favored the expansion of primary
      HSPCs.

PMID- 18724699
TI  - [Somatic hybridization between Brassica napus and Eruca sativa mill].
AB  - In order to expand gene resources and improve Brassica napus cultivars,
      protoplasts isolated from hypocotyls of Brassica napus cv. Huayou No. 3 and Eruca
      sativa were fused by PEG-high Ca2+-high pH. Fusion frequency was up to 18.2% when
      fusion system contained 5 x 10(5) protoplasts/mL, and when PEG concentration of
      fusion agents were 35% and when fusion time was 25 min. Then the fused
      protoplasts were cultured by the method of thin liquid layer at the density of 1
      x 10(5) protoplasts/mL in improved KM8p medium supplemented with 1.0 mg/L 2,4-D,
      0.5 mg/L NAA, 0.5 mg/L 6-BA, 200 mg/L inositol, 300 mg/L protein hydrolysate, and
      the combinations of 0.1 mol/L sucrose and 0.2 mol/L glucose and 0.2 mol/L
      mannitol for osmotic regulator, the frequency of callus regeneration was up to
      6.8%. When the micro-calli transferred to the proliferation medium that contained
      B5 salts, 0.087 mol/L sucrose, 0.2 mg/L 2,4-D, 0.5 mg/L NAA, 0.2 mg/L 6-BA and
      0.5% Agar, pH 5.8, have grown up to 3-5 mm of diameter, the calli were
      transferred to the differentiation medium that contained MS salts, 0.087 mol/L
      sucrose, 0.1 mg/L IAA, 0.8 mg/L 6-BA, 0.8% Agar, pH5.8, the shoots were
      regenerated in 4 weeks and its frequency was up to 32.8%. Then 2-3 cm shoots were
      transferred to 1/2 MS medium with 0.5 mg/L IBA+0.2mg/L 6-BA, plantlets were
      obtained in 14 days and the plantlet frequency was up to 88%. When the
      protoplasts of Eruca sativa were treated with UV radiation for 2 minutes calli
      and plantlets have been regenerated, treated for 4 min only calli have been
      regenerated, and treated for more than 5 min calli have not been regenerated. The
      callus regeneration and callus proliferation and plant regeneration from
      symmetric fusion were more than from asymmetric fusion. 16 hybrid plantlets have
      been regenerated on 21 piece of hybrid calli identified by cytology method.

PMID- 18724700
TI  - [Germination and propagartors of artificial seeds of Dendrobium huoshanense].
AB  - The artificial seeds of Dendrobium huoshanese was produced with Auxiliary buds,
      Protocorm-like bodies, and adventitious shoots. By using orthogonal experiment,
      we studied the effect of Maltose (%), hormone rate between 6-BA (mgx L(-1)) and
      NAA (mgL(-1)), active carbon (%), sodium alginate (%), time of ion exchange (min)
      on germination rate of artificial seeds of D. huoshanese. Then the leaking rate
      of maltose and variation of pH value of artificial seed capsule during vegetating
      of artificial seeds of D. huoshanese was measured. The results show that maltose
      played the most important role in inducing D. huoshanese artificial seeds to
      germinate. The optimal combination was: maltose 4%, hormone rate between 6-BA (mg
      x L(-1)) and NAA (mg x L(-1)) 10:1, active carbon 0.1%, sodium Alginate 4%, time
      of ion exchange is 10 min. Protocorm-like bodies were appropriate propagartor,
      the germination rate of artificial seeds of D. huoshanese takeing Protocorm-like
      bodies as the propagartors is 90.1%. After germination, the survival rate of
      seedlings of artificial seeds was 80.6%, the leaking rate of maltose of
      artificial seed capsule was 0.52%, and the pH value of artificial seed capsule
      decreased during the process of vegetation of artificial seeds. After having been
      stored at 4 degrees C for 20 d, the germination rate of artificial seeds of D.
      huoshanese takeing Auxiliary buds, Protocorm-like bodies, Adventitious shoots as
      the propagartors were 3.3%, 10.6%, 5.2%. Under natural conditions the germination
      rate was 13.8% after 10.0 g/L carbendazim was appended into artificial seed
      capsule. This result provides a foundation of manufacture and further study of
      the artificial seeds of D. huoshanese.

PMID- 18724701
TI  - [Transient gene expression of soluble VEGFR2: I-IV].
AB  - The extracelluar domain I-IV of target gene VEGFR2 (Vascular endothelial growth
      factor receptor 2) was cloned from villus of trimester abortion by RT-PCR, and
      linked to the expression vectors. Then, the transfection conditions were
      optimized in serum-free suspension culture HEK293 using GFP (Green fluorescence
      protein) as the report gene. The results showed that the optimal transfection
      efficiency and cell number were obtained when the ratio of foreign DNA: PEI = 1:2
      (W/W), DNA = 1.5 g /10(6) cells and shaking speed (120 r/min) in serum free
      medium in the beginning 4 hours of transfection. After optimizing the
      transfection conditions, the expression vector was successfully constructed for
      transient gene expression in HEK293, COS-7, and CHO-K1. The result shows that the
      target protein was only detected in CHO-K1 supernatant. Because of the C-terminal
      8-His tag of target protein, target protein was subsequently purified using Ni2+
      IDA and 5 mg purified protein was obtained in 1.5 L supernatant of CHOK1.

PMID- 18724702
TI  - [Immobilized lipase catalyzed synthesis of vitamin A plamitate].
AB  - The synthesis of vitamin A plamitate in organic solvent with vitamin A acetate
      and ethyl palmitate with immobilized lipase from Candida sp. was studied. The
      influences of solvent, the molar ratio of substrates, the reaction temperature
      and time, and the water concentration were optimized and the best result was
      obtained by transesterification from 0.100 g vitamin A acetate and 0.433 g ethyl
      palmitic, at 30 degrees C, in 10 mL petroleum ether, containing 0.2% of water
      (V/V), with 1.1 g lipase. In these conditions, the yield of vitamin A palmitate
      reached 83% in 12 h. The immobilized lipase was reused about 5 batches.

PMID- 18724703
TI  - [Cutinase production from short-chain organic acids by Thermobifida fusca].
AB  - We studied cutinase production from short-chain organic acids by Thermobifida
      fusca WSH03-11 to evaluate the possibility of converting municipal sludge to high
      value-added products. The optimum organic acid (8.0 g/L) and nitrogen source (1.5
      g/L) concentrations were determined by the single factor experiments with butyric
      acid, propionic acid and acetic acid as the carbon sources. When lactic acid was
      used as the carbon source, the optimum organic acid (3.0 g/L) and nitrogen source
      (1.0 g/L) concentrations were obtained. Cutinase production by T. fusca WSH03-11
      was further improved with butyric acid (by 31.0%), propionic acid (by 13.3%),
      acetic acid (by 43.8%) and lactic acid (by 73.2%) as carbon source, respectively,
      with the optimized cutin concentrations. Among these four short-chain organic
      acids, the average specific consumption rate of acetic acid was the highest,
      higher than that of propionic acid 1.3-folds, butyric acid 2.0-folds and lactic
      acid 2.2-folds. The highest cutinase activity reached 52.4 u/mL with butyric acid
      (8 g/L) as the sole carbon source, higher than that of lactic acid (3 g/L) 1.7
      folds, acetic acid (8 g/L) 2.5-folds and propionic acid (8 g/L) 3.2-folds. The
      yield of cutinase activity on lactic acid (12.70 u/mg) higher than that of
      butyric acid 1.4-folds, propionic acid 3.0-folds and acetic acid 3.8-folds. T.
      fusca WSH03-11 consumed acetic acid firstly in mixed acids carbon sources, and
      the consumption of butyric acid was inhibited. Further studies indicated that the
      consumption rate of butyrate was decreased by 66.7% in the presence of 0.5 g/L
      acetic acid in the mixed acids. This was the first report concerning the
      production of cutinase by T. fusca with mixed organic acids as the carbon
      sources. The results presented here provided a novel and efficient approach to
      produce high value-add products from municipal sludge, and also established a
      foundation for the industrial production of cutinase by T. fusca WSH03-11 with
      cheap carbon sources from the processing of municipal sludge.

PMID- 18724704
TI  - [GSH fermentation process modeling using entropy-criterion based RBF neural
      network model].
AB  - The prediction accuracy and generalization of GSH fermentation process modeling
      are often deteriorated by noise existing in the corresponding experimental data.
      In order to avoid this problem, we present a novel RBF neural network modeling
      approach based on entropy criterion. It considers the whole distribution
      structure of the training data set in the parameter learning process compared
      with the traditional MSE-criterion based parameter learning, and thus effectively
      avoids the weak generalization and over-learning. Then the proposed approach is
      applied to the GSH fermentation process modeling. Our results demonstrate that
      this proposed method has better prediction accuracy, generalization and
      robustness such that it offers a potential application merit for the GSH
      fermentation process modeling.

PMID- 18724705
TI  - [Construction of a new brewing yeast strain with secretive alpha-amylase activity
      and reduced diacetyl production].
AB  - Saccharomycopsis fibuligera possesses high alpha-amylase and glucoamylase
      activities that enable it to utilize raw starch as a carbon source. A expression
      cassette containing the promoter sequence of 3-phosphogylycerate kinase gene
      (PGK1p), the alpha factor signal sequence from Saccharomyces cerevisiae and the
      alpha-amylase coding sequence of S. fibuligera was constructed. The alpha-amylase
      expression cassette was inserted in the ILV2 locus of industrial brewer's yeast
      strain YSF-5 encoding alpha-acetolactate synthase (AHAS) by homologous
      recombination. The transformed yeast strain was selected on the media with starch
      as the sole carbon source and verified by PCR. The transformant exhibited
      secretive alpha-amylase activity, low AHAS activity and reduced diacetyl
      production. Effects of temperature, pH, and metal ions on the activity of the
      alpha-amylase expressed by the transformant were examined. The fermentation
      performance of host strain YSF-5 and the transformant was also examined.

PMID- 18724706
TI  - [Regulation of key enzymes in tryptophan biosynthesis pathway in Escherichia
      coli].
AB  - To improve tryptophan production in Escherichia coli, key genes in the tryptophan
      biosynthesis pathway -aroG, trpED, trpR and tnaA were manipulated. TrpR gene was
      knocked out to eliminate the repression on the key genes controlling tryptophan
      biosynthesis and transportation on bacteria chromosome, and the tryptophan
      degradation was blocked by tnaA gene knockout. Then the bottleneck in tryptophan
      biosynthesis pathway was removed by co-expressing aroGfbr gene and trpEDfbr gene.
      Compared with the MG1655, the tryptophan production of trpR knockout and double
      genes knockout strains was improved 10-folds and about 20-folds, respectively.
      After the trpEDfbr was expressed, the tryptophan production increased to 168
      mg/L, and when the aroGfbr and trpEDfbr were co-expressed, the tryptophan
      production increased to 820 mg/L. This work laid the foundation for further
      construction of higher-efficient engineered strain for tryptophan production.

PMID- 18724707
TI  - Computational and structural investigation of deleterious functional SNPs in
      breast cancer BRCA2 gene.
AB  - In this work, we have analyzed the genetic variation that can alter the
      expression and the function in BRCA2 gene using computational methods. Out of the
      total 534 SNPs, 101 were found to be non synonymous (nsSNPs). Among the 7 SNPs in
      the untranslated region, 3 SNPs were found in 5' and 4 SNPs were found in 3' un
      translated regions (UTR). Of the nsSNPs 20.7% were found to be damaging by both
      SIFT and PolyPhen server among the 101 nsSNPs investigated. UTR resource tool
      suggested that 2 SNPs in the 5' UTR region and 4 SNPs in the 3' UTR regions might
      change the protein expression levels. The mutation from asparagine to isoleucine
      at the position 3124 of the native protein of BRCA2 gene was most deleterious by
      both SIFT and PolyPhen servers. A structural analysis of this mutated protein and
      the native protein was made which had an RMSD value of 0.301 nm. Based on this
      work, we proposed that this most deleterious nsSNP with an SNPid rs28897759 is an
      important candidate for the cause of breast cancer by BRCA2 gene.

PMID- 18724708
TI  - [The rescue of H1N1 subtype swine influenza virus].
AB  - The swine influenza virus (SIV) strain A/Swine/TianJin/01/2004(H1N1) (A/S/TJ/04)
      was rescued successfully by an eight-plasmid rescue system. The cDNAs of SIV 8
      gene segments were synthesized by RT-PCR and cloned into the RNA polymerase I/II
      bidirection expression vector PHW2000 independently, resulting in 8 recombinant
      plasmids. The 8 recombinant plasmids were cotransfected into COS-1 cell, 30 h
      later TPCK-trypsin was added to 0.5 microg/mL. The COS-1 cell and supernatant
      were harvested 48 h after cotransfection and were inoculated into the allantoic
      cavity of 9-day-old specific-pathogen free (SPF) chicken eggs. The allantoic
      fluid of dead eggs was harvested and passaged 3 generations in SPF chicken eggs
      to get infective virus. The successful rescue of A/S/TJ/04 SIV was identified by
      hemagglutination assay, hemagglutination inhibition assay, sequence analysis and
      electron microscope observation. The successful rescue of SIV built a platform
      for the research of the relationship between genome structure and function of
      SIV, the mechanisms of trans-species transmission of influenza virus and for the
      generation of new SIV as vaccine.

PMID- 18724709
TI  - [Stability analysis of CHO cell line expressing heterologous rhBMP2].
AB  - Bone morphogenetic protein 2 (BMP2), which belongs to the transforming growth
      factor-beta (TGF-beta) superfamily, is a multifunctional molecule with distinct
      abilities to induce bone formation. BMP2 has been identified to have eminent
      pharmaceutical importance for clinical application. We previously constructed
      stable cell line in Chinese hamster ovary cells (CHO) that highly expressed
      recombinant human BMP2 (rhBMP2). For large-scale production of the recombinant
      protein used in clinical application, it is critical to have both high expression
      and stability of the protein. In the present study, the stability of the cell
      line (rCHO(hBMP2)-C8) with the highest expression, as well as the stability of
      rhBMP2 protein were investigated systematically. We cultured the rCHO (hBMP2)-C8
      cell line in the presence or absence of MTX for two months, the cell growth and
      rhBMP2 production characteristics were examined during the culture; we found the
      duration that the rCHO(hBMP2)-C8 cell line could secret rhBMP2 continually into
      the serum-free medium. Moreover, we detected the temperature sensitivity of
      rhBMP2 in culture medium. This study will contribute to our understanding for
      further producing rhBMP2 by large-scale culture technology.

PMID- 18724710
TI  - [Purification and characterization of a beta-D-xylosidase from Leifsonia
      shinshuensis DICP 16].
AB  - A beta-D-xylosidase from Leifsonia shinshuensis DICP 16 was purified to apparent
      homogeneity using a combination of ammonium sulfate precipitation, DE 52 anion
      exchange, Q-Sepharose Fast Flow anion-exchange, Toyopearl Butyl 650C hydrophobic
      interaction and Sephacryl S-300 HR gel-permeation chromatography. The purified
      xylosidase consisted of two same subunits and had the relative molecular weight
      of 180 kD as determined by SDS-PAGE and gel-permeation chromatography. The
      maximal beta-D-xylosidase activity occurred at 55 degrees C and pH 7.0. It was
      stable at 45 degrees C and retained its original activity for 60 min. The
      stability declined rapidly when the temperature rose above 55 degrees C. The
      xylosidase was stable in the pH range from 6.0 to 11.0 for 20 h. At pH 7.0 and 45
      degrees C the Km for p-nitrophenyl-beta-D-xylopyranoside (pNPX) was 1.04 mmol/L
      and the Vmx was 0.095 mmol nitrophenol/min/mg xylosidase. The enzyme was
      inhibited strongly by Fe2+ and Cu2+. It exhibited low levels of activity against
      other artificial substrates, compared to its activity against pNPX. When
      different natural xylosides were used as the substrates, the xylosidase showed
      distinct hydrolysis ability. It could hydrolyze 20-C, beta-(1-->6)-xyloside of
      ginsenoside Rb3 (G-Rb3) into ginsenoside Rd, but did not hydrolyze the other beta
      D-glucosidic bonds of G-Rb3. Additionally, the xylosidase could not hydrolyze C-7
      xylosyl-bearing taxanes.

PMID- 18724711
TI  - [Cloning of foot-and-mouth disease virus integrin receptor beta1 subunit and
      antibody production to its ligand-binding domain].
AB  - We produced beta1 gene which is about 2400 bp by reverse transcription polymerase
      chain reaction (RT-PCR) from bovine trachea, reclaimed and purified, then cloned
      the amplified fragment to pGEM-T easy vector, confirmed by sequencing. The immune
      dominant epitope of beta1 gene was chosen by computer analysis and then
      syncretized ligand-binding domain from 346 bp to 843 bp of ecytoplasm with six
      histidine, expressed LBD protein massly in E. coli BL21 (DE3), and identified by
      SDS-PAGE. The fusion protein was purified with Ni-NTA affinity chromatography and
      immunized New Zealand rabbits preparing of its polyclonal antibody, the specific
      antibody titer was above 1:12,800 detected by indirect ELISA, the result of
      Western blot showed that this antibody could be recognized by LBD fusion protein.

PMID- 18724712
TI  - [The pTA29-barnase chimeric gene transformation of Brassica campestris L. subsp.
      chinensis Makino var. parachinensis mediated by agrobacterium].
AB  - In order to induce male sterility of Brassica campestris L. subsp. chinensis
      Makino var. parachinensis, we introduced the chimeric pTA29-barnase gene into it
      by Agrobacteriumtume faciens transformation. We obtained the transgenic plants,
      and determined them by PCR, Southern blotting and RT-PCR analysis. Results
      indicated that the RNase (barnase) gene had been transferred into genome of
      plant, and its expression level was different among transformation plants. All
      transgenic plants were male sterile; there was no vigor or a little pollen
      without fertility in the anther of transgenic plants. The transgenic plants
      failed to produce seeds under the condition self-control pollination, but hybrid
      seeds set were obtained when these transgenic plants were cross-pollinated
      artificially with normal pollen from untransformed plants. Progeny from cross
      pollinated maintainer line with transgenic plants segregated in the 1:1 for male
      sterility and male fertility, and these phenotypes corresponded directly to the
      presence or absence of the chimeri TA29-barnase gene. The male fertile plants of
      co-separated progenies could die by spraying 10 mg/L PPT in cotyledon seedling
      stage. The hybrid F1 between male sterility and other varieties showed heterosis
      in yield and growth. All these show that it is an efficient method to induce male
      sterility in Brassica campestris L. subsp. chinensis Makino var. parachinensis by
      TA29-barnase ene, there is potential on heterosis breeding of Brassica campestris
      L. subsp. chinensis Makino var. parachinensis.

PMID- 18724713
TI  - [Effect of different tags on pulldown assays implemented by LMO2 fusion protein].
AB  - Pulldown assay is an in vitro method for studies of protein-protein interactions,
      in which tagged proteins are usually expressed as the bait to enrich other
      proteins that could bind to them. In this technology, the GST tag is broadest
      used for its modest size and hydrophilic property. In most cases, the GST tag
      could increase the hydrophility of the fusion protein and help to avoid the
      formation of inclusion bodies. However, in the other few cases, the target
      protein may be strongly hydrophobic or have complicated structures that were hard
      to fold and assemble in correct conformations without champerons, and even the
      existence of GST tag could not make them soluble. These proteins were always
      expressed as inclusion bodies and had no functions. LMO2 was a small molecular
      weight and insoluble protein, in this study, GST system and MBP system were used
      to express GST-LMO2 and MBP-LMO2 fusion proteins, respectively. We found that GST
      LMO2 fusion protein was expressed as inclusion bodies whereas MBP-LMO2 fusion
      protein was expressed in soluble form. Moreover, the production rate of MBP-LMO2
      was also much higher than GST-LMO2. Then MBP-LMO2 fusion proteins and renatured
      GST-LMO2 fusion proteins were used as bait in pulldown assay to study the
      interaction between LMO2 and endogenous GATA1 in K562 cells. Western blot
      analyses showed that both of these proteins could bind to endogenous GATA1 in
      K562 cells, but recovered GATA1 protein by MBP-LMO2 fusion protein was much more
      than GST-LMO2 fusion protein. These results suggest that using of MBP system is a
      helpful attempt in the case of studying small molecular weight, strong
      hydrophobic proteins.

PMID- 18724714
TI  - [Development and application of real-time quantitative RT- PCR assay for the
      detection of hepatitis E virus].
AB  - Hepatitis E virus (HEV) sequences including four major genotypes representative
      strains available in GenBank were aligned with the DNAMAN software. The highly
      conserved internal region of ORF2 was then subjected to design primers and a
      probe. Furthermore, a 0.3 kb fragment of HEV ORF2 containing the amplification
      region was transcribed in vitro to synthese cRNA standard and a universal real
      time TaqMan PCR assay was optimized and developed to detect and quantify main
      genotypes RNA of HEV. The specificity and reliability of the real-time RT-PCR was
      confirmed by testing genotype I HEV, genotype IV HEV and clinical samples. The
      detection limit of real-time RT-PCR was found 2.0 x 10(1) copies per reaction
      using in vitro transcribed cRNA. Compared with nested RT-PCR in diagnosis of HEV,
      the real-time RT-PCR developed was 10 to 100-fold more sensitive than the nested
      RT-PCR. The detection results from 54 clinical specimens indicated real-time RT
      PCR was a rapid, sensitive and reproducible diagnostic method for HEV. This assay
      will be useful as an early and rapid diagnostic assay for HEV.

PMID- 18724715
TI  - [Synthesis and identification of penicillic-acid antigens from Penicillium
      cyclopium].
AB  - To establish a new immune assay for Penicillic Acid (PA) from Penicillium
      cyclopium, we studied the synthesis of conjugated complete antigens for
      penicillic acid. PA was conjugated to bovine serum album (BSA) and ovalbumin
      (OVA) by 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide hydrochloride (EDC). The
      artificial antigens PA-BSA and PA-OVA were identified by ultraviolet
      spectrometric scanning, SDS-PAGE and immunization. Results showed that the
      absorption peak of conjugation were different from that of the carrier protein
      alone and of the PA. The conjugated ratio of PA and BSA was 23.2:1 and that of PA
      and OVA was 10.4:1. Balb/c mice were immunized by the artificial antigen of PA
      BSA, with PA-OVA as coating antigen. The average titer of antiserums was more
      than 12 800 by indirect ELISA. The obtained antigens offered a basis for
      developing immunoassay method.

PMID- 18724716
TI  - [Prokaryotic expression and purification of moloney murine leukemia virus reverse
      transcriptase and verification of the activity].
AB  - To produce the reverse transcriptase of moloney murine leukemia virus (MMLV-RT)
      through gene recombination, MMLV-rt gene was amplified by polymerase chain
      reaction (PCR) with specifically designed primers bearing restriction enzyme
      sites. Five mutation sites increasing the solution of the target protein were
      introduced through Site-directed mutation. After verification by sequencing, the
      gene was cloned into the expression vector pET15b to construct the recombinant
      plasmid pET15b-MMLV-rt. Purified MMLV-RT was obtained by affinity chromatography
      (Ni3+-NTA beads). Molecular weight and purity of MMLV-RT were analyzed with SDS
      PAGE. Enzyme activity was characterized with RT-PCR. We successfully constructed
      the recombinant plasmid pET15b-MMLV-rt and obtained the MMLV-RT fusion protein
      with 6His on the N-terminus. Recombinant protein was purified through Ni3+-NTA
      beads based affinity chromatography, the purity of which was 96%. The Activity of
      the enzyme was high. MMLV-RT of 96% purity was obtained with the prokaryotic
      expression technique, which serves as the basis for mass production of this
      enzyme.

PMID- 18724717
TI  - Quantifying the complexities of Saccharomyces cerevisiae's ecosystem engineering
      via fermentation.
AB  - The theory of niche construction suggests that organisms may engineer
      environments via their activities. Despite the potential of this phenomenon being
      realized by Darwin, the capability of niche construction to generally unite
      ecological and evolutionary biology has never been empirically quantified. Here I
      quantify the fitness effects of Saccharomyces cerevisiae's ecosystem engineering
      in a natural ferment in order to understand the interaction between ecological
      and evolutionary processes. I show that S. cerevisiae eventually dominates in
      fruit niches, where it is naturally initially rare, by modifying the environment
      through fermentation (the Crabtree effect) in ways which extend beyond just
      considering ethanol production. These data show that an additional cause of S.
      cerevisiae's competitive advantage over the other yeasts in the community is due
      to the production of heat via fermentation. Even though fermentation is less
      energetically efficient than respiration, it seems that this trait has been
      selected for because its net effect provides roughly a 7% fitness advantage over
      the other members of the community. These data provide an elegant example of
      niche construction because this trait clearly modifies the environment and
      therefore the selection pressures to which S. cerevisiae, and other organisms
      that access the fruit resource, including humans, are exposed to.

PMID- 18724718
TI  - Estimating nonlinear interaction strengths: an observation-based method for
      species-rich food webs.
AB  - Efforts to estimate the strength of species interactions in species-rich,
      reticulate food webs have been hampered by the multitude of direct and indirect
      interactions such systems exhibit and have been limited by an assumption that
      pairwise interactions display linear functional forms. Here we present a new
      method for directly measuring, on a per capita basis, the nonlinear strength of
      trophic species interactions within such food webs. This is an observation-based
      method, requiring three pieces of information: (1) species abundances, (2)
      predator and prey-specific handling times, and (3) data from predator-specific
      feeding surveys in which the number of individuals observed feeding on each of
      the predator's prey species has been tallied. The method offers a straightforward
      way to assess the completeness of one's sampling effort in accurately estimating
      interaction strengths through the construction of predator-specific prey
      accumulation curves. The method should be applicable to a variety of systems in
      which empirical estimates of direct interaction strengths have thus far remained
      elusive.

PMID- 18724719
TI  - Indirect effects of an exploited predator on recruitment of coral-reef fishes.
AB  - The more ecologists examine the role of trait-mediated indirect interactions
      (TMIIs), especially in regulating predator-prey interactions, the more we
      recognize their fundamental role in structuring food webs. However, most
      empirical evidence for TMIIs comes from studies that are either conducted in
      laboratory or mesocosm venues or are restricted to simple food webs involving
      lower trophic-level animals. Here, I quantified the direct and indirect effects
      of interactions between high-level vertebrate predators on their vertebrate prey
      using a field experiment. Specifically, I tested how varying densities of a large
      bodied, top predator (Nassau grouper; Epinephelus striatus) affected persistence,
      growth, and behavior of two smaller-bodied, intermediate predators (coney and
      graysby groupers; Cephalopholis fulva and C. cruentata) on 20 isolated patch
      reefs in the Bahamas. Large-bodied groupers are capable of consuming their
      smaller-bodied counterparts, and previous observational studies have indicated
      that local abundances of these groupers are negatively correlated. I measured the
      effects of interactions among groupers on lower trophic-level prey by quantifying
      recruitment of coral-reef fishes to the reefs. The field experiment demonstrated
      a strong trophic cascade that was entirely mediated by modified behavior of the
      intermediate predators. These results indicate that indirect, nonlethal
      interactions in natural systems can have strong cascading effects even at high
      trophic levels and in high-diversity food webs. Incorporating the complexity of
      such indirect effects into fisheries management may improve the sustainability of
      fished populations and strengthen marine conservation efforts; however these
      results also indicate that the effects of fishing are complex and difficult to
      predict.

PMID- 18724720
TI  - Sea ice cover and its influence on Adelie Penguin reproductive performance.
AB  - The relationship between Adelie Penguins (Pygoscelis adeliae) and ice is well
      established, with sea ice influencing penguin populations through a variety of
      processes operating at different spatial and temporal scales. To further explain
      the relationship between sea ice and Adelie Penguin reproductive performance, we
      investigated the relative importance of various measures of sea ice cover on
      breeding success at Bechervaise Island, East Antarctica. Our results show a clear
      distinction in the response of penguins to different types of ice, as well as to
      the timing of the presence of sea ice. Nearshore sea ice, which is composed
      primarily of fast ice during the guard stage of the breeding season, had an
      overwhelmingly strong and negative impact on penguin reproductive performance.
      The influence of winter and offshore guard-stage ice was only evident in
      conjunction with nearshore ice. Predicting Adelie Penguin population growth in
      relation to changes in the sea ice environment may be complicated because penguin
      ice interactions vary according to the type of sea ice present, the season in
      which it is present, and the processes contributing to population growth that are
      influenced by sea ice.

PMID- 18724721
TI  - Habitat type determines herbivory controls over CO2 fluxes in a warmer Arctic.
AB  - High-latitude ecosystems store large amounts of carbon (C); however, the C
      storage of these ecosystems is under threat from both climate warming and
      increased levels of herbivory. In this study we examined the combined role of
      herbivores and climate warming as drivers of CO2 fluxes in two typical high
      latitude habitats (mesic heath and wet meadow). We hypothesized that both
      herbivory and climate warming would reduce the C sink strength of Arctic tundra
      through their combined effects on plant biomass and gross ecosystem
      photosynthesis and on decomposition rates and the abiotic environment. To test
      this hypothesis we employed experimental warming (via International Tundra
      Experiment [ITEX] chambers) and grazing (via captive Barnacle Geese) in a three
      year factorial field experiment. Ecosystem CO2 fluxes (net ecosystem exchange of
      CO2, ecosystem respiration, and gross ecosystem photosynthesis) were measured in
      all treatments at varying intensity over the three growing seasons to capture the
      impact of the treatments on a range of temporal scales (diurnal, seasonal, and
      interannual). Grazing and warming treatments had markedly different effects on
      CO2 fluxes in the two tundra habitats. Grazing caused a strong reduction in CO2
      assimilation in the wet meadow, while warming reduced CO2 efflux from the mesic
      heath. Treatment effects on net ecosystem exchange largely derived from the
      modification of gross ecosystem photosynthesis rather than ecosystem respiration.
      In this study we have demonstrated that on the habitat scale, grazing by geese is
      a strong driver of net ecosystem exchange of CO2, with the potential to reduce
      the CO2 sink strength of Arctic ecosystems. Our results highlight that the large
      reduction in plant biomass due to goose grazing in the Arctic noted in several
      studies can alter the C balance of wet tundra ecosystems. We conclude that
      herbivory will modulate direct climate warming responses of Arctic tundra with
      implications for the ecosystem C balance; however, the magnitude and direction of
      the response will be habitat-specific.

PMID- 18724722
TI  - Global potential net primary production predicted from vegetation class,
      precipitation, and temperature.
AB  - Net primary production (NPP), the difference between CO2 fixed by photosynthesis
      and CO2 lost to autotrophic respiration, is one of the most important components
      of the carbon cycle. Our goal was to develop a simple regression model to
      estimate global NPP using climate and land cover data. Approximately 5600 global
      data points with observed mean annual NPP, land cover class, precipitation, and
      temperature were compiled. Precipitation was better correlated with NPP than
      temperature, and it explained much more of the variability in mean annual NPP for
      grass- or shrub-dominated systems (r2 = 0.68) than for tree-dominated systems (r2
      = 0.39). For a given precipitation level, tree-dominated systems had
      significantly higher NPP (approximately 100-150 g C m(-2) yr(-1)) than non-tree
      dominated systems. Consequently, previous empirical models developed to predict
      NPP based on precipitation and temperature (e.g., the Miami model) tended to
      overestimate NPP for non-tree-dominated systems. Our new model developed at the
      National Center for Ecological Analysis and Synthesis (the NCEAS model) predicts
      NPP for tree-dominated systems based on precipitation and temperature; but for
      non-tree-dominated systems NPP is solely a function of precipitation because
      including a temperature function increased model error for these systems. Lower
      NPP in non-tree-dominated systems is likely related to decreased water and
      nutrient use efficiency and higher nutrient loss rates from more frequent fire
      disturbances. Late 20th century aboveground and total NPP for global potential
      native vegetation using the NCEAS model are estimated to be approximately 28 Pg
      and approximately 46 Pg C/yr, respectively. The NCEAS model estimated an
      approximately 13% increase in global total NPP for potential vegetation from 1901
      to 2000 based on changing precipitation and temperature patterns.

PMID- 18724723
TI  - Quantifying the abundance of co-occurring conifers along Inland Northwest (USA)
      climate gradients.
AB  - The occurrence and abundance of conifers along climate gradients in the Inland
      Northwest (USA) was assessed using data from 5082 field plots, 81% of which were
      forested. Analyses using the Random Forests classification tree revealed that the
      sequential distribution of species along an altitudinal gradient could be
      predicted with reasonable accuracy from a single climate variable, a growing
      season dryness index, calculated from the ratio of degree-days >5 degrees C that
      accumulate in the frost-free season to the summer precipitation. While the
      appearance and departure of species in an ascending altitudinal sequence were
      closely related to the dryness index, the departure was most easily visualized in
      relation to negative degree-days (degree-days < 0 degrees C). The results were in
      close agreement with the works of descriptive ecologists. A Weibull response
      function was used to predict from climate variables the abundance and occurrence
      probabilities of each species, using binned data. The fit of the models was
      excellent, generally accounting for >90% of the variance among 100 classes.

PMID- 18724724
TI  - Primary production and rain use efficiency across a precipitation gradient on the
      Mongolia Plateau.
AB  - Understanding how the aboveground net primary production (ANPP) of arid and
      semiarid ecosystems of the world responds to variations in precipitation is
      crucial for assessing the impacts of climate change on terrestrial ecosystems.
      Rain-use efficiency (RUE) is an important measure for acquiring this
      understanding. However, little is known about the response pattern of RUE for the
      largest contiguous natural grassland region of the world, the Eurasian Steppe.
      Here we investigated the spatial and temporal patterns of ANPP and RUE and their
      key driving factors based on a long-term data set from 21 natural arid and
      semiarid ecosystem sites across the Inner Mongolia steppe region in northern
      China. Our results showed that, with increasing mean annual precipitation (MAP),
      (1) ANPP increased while the interannual variability of ANPP declined, (2) plant
      species richness increased and the relative abundance of key functional groups
      shifted predictably, and (3) RUE increased in space across different ecosystems
      but decreased with increasing annual precipitation within a given ecosystem.
      These results clearly indicate that the patterns of both ANPP and RUE are scale
      dependent, and the seemingly conflicting patterns of RUE in space vs. time
      suggest distinctive underlying mechanisms, involving interactions among
      precipitation, soil N, and biotic factors. Also, while our results supported the
      existence of a common maximum RUE, they also indicated that its value could be
      substantially increased by altering resource availability, such as adding
      nitrogen. Our findings have important implications for understanding and
      predicting ecological impacts of global climate change and for management
      practices in arid and semiarid ecosystems in the Inner Mongolia steppe region and
      beyond.

PMID- 18724725
TI  - Plant-soil feedback: testing the generality with the same grasses in serpentine
      and prairie soils.
AB  - Plants can alter soil properties in ways that feed back to affect plant
      performance. The extent that plant-soil feedback affects co-occurring plant
      species differentially will determine its impact on plant community structure.
      Whether feedback operates consistently across similar plant communities is little
      studied. Here, the same grasses from two eastern U.S. serpentine grasslands and
      two midwestern tallgrass prairie remnants were examined for plant-soil feedback
      in parallel greenhouse experiments. Native soils were homogenized and cultured
      (trained) for a year with each of the four grasses. Feedback was evaluated by
      examining biomass variation in a second generation of (tester) plants grown in
      the trained soils. Biomass was lower in soils trained by conspecifics compared to
      soils trained by heterospecifics in seven of 15 possible cases; biomass was
      greater in conspecific soils in one other. Sorghastrum nutans exhibited lower
      biomass in conspecific soils for all four grasslands, so feedback may be
      characteristic of this species. Three cases from the Hayden prairie site were
      explained by trainer species having similar effects across all tester species so
      the relative performance of the different species was little affected; plants
      were generally larger in soils trained by Andropogon gerardii and smaller in
      soils trained by S. nutans. Differences among sites in the incidence of feedback
      were independent of serpentine or prairie soils. To explore the causes of the
      feedback, several soil factors were measured as a function of trainer species:
      nutrients and pH, arbuscular mycorrhizal (AM) spore communities, root
      colonization by AM fungi and putative pathogens, and functional diversity in
      bacterial communities as indicated by carbon substrate utilization. Only
      variation in nutrients was consistent with any patterns of feedback, and this
      could explain the greater biomass in soils trained by A. gerardii at Hayden.
      Feedback at Nottingham (one of the serpentine sites) differed, most notably for
      A. gerardii, from that of similar past studies that used different experimental
      protocols. To understand the consequences of feedback for plant community
      structure, it is important to consider how multiple species respond to the same
      plant-induced soil variation as well as differences in the feedback detected
      between greenhouse and field settings.

PMID- 18724726
TI  - Scale-dependent responses of plant biodiversity to nitrogen enrichment.
AB  - Experimental studies demonstrating that nitrogen (N) enrichment reduces plant
      diversity within individual plots have led to the conclusion that anthropogenic N
      enrichment is a threat to global biodiversity. These conclusions overlook the
      influence of spatial scale, however, as N enrichment may alter beta diversity
      (i.e., how similar plots are in their species composition), which would likely
      alter the degree to which N-induced changes in diversity within localities
      translate to changes in diversity at larger scales that are relevant to policy
      and management. Currently, it is unclear how N enrichment affects biodiversity at
      scales larger than a small plot. We synthesized data from 18 N-enrichment
      experiments across North America to examine the effects of N enrichment on plant
      species diversity at three spatial scales: small (within plots), intermediate
      (among plots), and large (within and among plots). We found that N enrichment
      reduced plant diversity within plots by an average of 25% (ranging from a
      reduction of 61% to an increase of 5%) and frequently enhanced beta diversity.
      The extent to which N enrichment altered beta diversity, however, varied
      substantially among sites (from a 22% increase to an 18% reduction) and was
      contingent on site productivity. Specifically, N enrichment enhanced beta
      diversity at low-productivity sites but reduced beta diversity at high
      productivity sites. N-induced changes in beta diversity generally reduced the
      extent of species loss at larger scales to an average of 22% (ranging from a
      reduction of 54% to an increase of 18%). Our results demonstrate that N
      enrichment often reduces biodiversity at both local and regional scales, but that
      a focus on the effects of N enrichment on biodiversity at small spatial scales
      may often overestimate (and sometimes underestimate) declines in regional
      biodiversity by failing to recognize the effects of N on beta diversity.

PMID- 18724727
TI  - Perturbations alter community convergence, divergence, and formation of multiple
      community states.
AB  - Environmental perturbations (e.g., disturbance, fertilization) commonly shift
      communities to a new mean state, but much less is known about their effects on
      the variability (dispersion) of communities around the mean, particularly when
      perturbations are combined. Community dispersion may increase or decrease
      (representing a divergence or convergence among communities) if changing
      environmental conditions alter species interactions or magnify small initial
      differences that develop during community assembly. We used data from an
      experimental study of disturbance and fertilization in a low-productivity
      grassland to test how these two perturbations affect patterns of species
      composition and abundance. We found that a one-time biomass reduction decreased
      community dispersion, which persisted over four growing seasons. Conversely,
      continuous fertilization increased community dispersion and, when combined with
      disturbance, led to the formation of three distinct community states. These
      results illustrate that perturbations can have differing effects on community
      dispersion. Attention to the variance in community responses to perturbations
      lends insight into how ecological interactions determine community structure,
      which may be missed when focusing only on mean responses. Furthermore, multiple
      perturbations may have complex effects on community dispersion, yielding
      convergence or divergence patterns that are difficult to predict based on
      analysis of single factors.

PMID- 18724728
TI  - Fire reduces morphospace occupation in plant communities.
AB  - The two main assembly processes claimed to structure plant communities are
      habitat filtering and competitive interactions. The set of species growing in
      fire-prone communities has been filtered in such a way that species without fire
      persistence traits have not successfully entered the community. Because plant
      traits are evolutionarily conserved and fire traits are correlated with other
      plant traits, communities under high fire frequency should not include all
      possible trait combinations, and thus the morphospace occupation by species in
      these communities should be lower than expected by chance (underoccupied). In
      contrast, communities under low fire frequency would lack the filtering factor,
      and thus their underoccupation of the morphospace is not expected. We test this
      prediction by comparing the morphospace occupation by species in communities
      located in the western Mediterranean Basin, five of them subject to high fire
      frequency (HiFi) and four to low fire frequency (LowFi). We first compile a set
      of morphological and functional traits for the species growing on the nine sites,
      then we compute the morphospace occupation of each site as a convex hull volume,
      and finally, to assert that our results are not a product of a random branching
      pattern of evolution, we simulate our traits under a null model of neutral
      evolution and compare the morphospace occupation of the simulated traits with the
      results from the empirical data. The results suggest that, as predicted, there is
      a clear differential morphospace occupation between communities under different
      fire regimes in such a way that the morphospace is underoccupied in HiFi
      communities only. The simulation of a neutral evolutionary model does not
      replicate the observed pattern of differential morphospace occupation, and thus
      it should be attributed to assembly processes. In conclusion, our results suggest
      that fire is a strong community assembling process, filtering the species that
      have fire-persistent traits and thus assembling phenotypically and
      phylogenetically clustered communities with vacant zones in the morphospace.

PMID- 18724729
TI  - Coexistence of three specialist aphids on common milkweed, Asclepias syriaca.
AB  - Coexistence of host-specific herbivores on plants is believed to be governed by
      interspecific interactions, but few empirical studies have systematically
      unraveled these dynamics. We investigated the role of several factors in
      promoting coexistence among the aphids Aphis nerii, Aphis asclepiadis, and
      Myzocallis asclepiadis that all specialize on common milkweed (Asclepias
      syriaca). Competitive exclusion is thought to occur when interspecific
      competition is stronger than intraspecific competition. Consequently, we
      investigated whether predators, mutualists, or resource quality affected the
      strength of intra- vs. interspecific competition among aphids in factorial
      manipulations of competition with exposure to predation, ants, and variable plant
      genotypes in three separate experiments. In the predation x competition
      experiment, predators reduced aphid per capita growth by 66%, but the strength of
      intra- and interspecific competition did not depend on predators. In the ants x
      competition experiment, ants reduced per capita growth of A. nerii and M.
      asclepiadis (neither of which were mutualists with ants) by approximately one
      half. In so doing, ants ameliorated the negative effects of these competitors on
      ant-tended A. asclepiadis by two-thirds, representing a novel benefit of ant
      aphid mutualism. Nevertheless, ants alone did not explain the persistence of
      competitively inferior A. asclepiadis as, even in the presence of ants,
      interspecific competition remained stronger than intraspecific competition. In
      the plant genotype x competition experiment, both A. asclepiadis and M.
      asclepiadis were competitively inferior to A. nerii, with the strength of
      interspecific competition exceeding that of intraspecific competition by 83% and
      23%, respectively. Yet these effects differed among milkweed genotypes, and there
      were one or more plant genotypes for each aphid species where coexistence was
      predicted. A synthesis of our results shows that predators play little or no role
      in preferentially suppressing competitively dominant A. nerii. Nonetheless, A.
      asclepiadis benefits from ants, and A. asclepiadis and M. asclepiadis may escape
      competitive exclusion by A. nerii on select milkweed genotypes. Taken as a whole,
      the coexistence of three host-specific aphid species sharing the same resource
      was promoted by the dual action of ants as antagonists and mutualists and by
      genetic diversity in the plant population itself.

PMID- 18724730
TI  - Evolution of polyploidy and the diversification of plant-pollinator interactions.
AB  - One of the major mechanisms of plant diversification has been the evolution of
      polyploid populations that differ from their diploid progenitors in morphology,
      physiology, and environmental tolerances. Recent studies have indicated that
      polyploidy may also have major effects on ecological interactions with herbivores
      and pollinators. We evaluated pollination of sympatric diploid and tetraploid
      plants of the rhizomatous herb Heuchera grossulariifolia (Saxifragaceae) along
      the Selway and Salmon Rivers of northern Idaho, USA, during four consecutive
      years. Previous molecular and ecological analyses had indicated that the
      tetraploid populations along these two river systems are independently derived
      and differ from each other in multiple traits. In each region, we evaluated
      floral visitation rate by all insect visitors, pollination efficacy of all major
      visitors, and relative contribution of all major pollinators to seed set. In both
      regions, diploid and tetraploid plants attracted different suites of floral
      visitors. Most pollination was attributable to several bee species and the moth
      Greya politella. Lasioglossum bees preferentially visited diploid plants at Lower
      Salmon but not at Upper Selway, queen Bombus centralis preferentially visited
      tetraploids at both sites, and worker B. centralis differed between sites in
      their cytotype preference. Hence, diploid and autotetraploid H. grossulariifolia
      plants act essentially as separate ecological species and may experience partial
      reproductive isolation through differential visitation and pollination by their
      major floral visitors. Overall the results, together with recent results from
      other studies, suggest that the repeated evolution of polyploidy in plants may
      contribute importantly to the structure and diversification of ecological
      interactions in terrestrial communities.

PMID- 18724731
TI  - Nectar secondary compounds affect self-pollen transfer: implications for female
      and male reproduction.
AB  - Pollen movement within and among plants affects inbreeding, plant fitness, and
      the spatial scale of genetic differentiation. Although a number of studies have
      assessed how plant and floral traits influence pollen movement via changes in
      pollinator behavior, few have explored how nectar chemical composition affects
      pollen transfer. As many as 55% of plants produce secondary compounds in their
      nectar, which is surprising given that nectar is typically thought to attract
      pollinators. We tested the hypothesis that nectar with secondary compounds may
      benefit plants by encouraging pollinators to leave plants after visiting only a
      few flowers, thus reducing self-pollen transfer. We used Gelsemium sempervirens,
      a plant whose nectar contains the alkaloid gelsemine, which has been shown to be
      a deterrent to foraging bee pollinators. We found that high nectar alkaloids
      reduced the total and proportion of self-pollen received by one-half and one
      third, respectively. However, nectar alkaloids did not affect female reproduction
      when we removed the potential for self-pollination (by emasculating all flowers
      on plants). We then tested the assumption that self-pollen in combination with
      outcrossed pollen depresses seed set. We found that plants were weakly self
      compatible, but self-pollen with outcrossed pollen did not reduce seed set
      relative to solely outcrossed flowers. Finally, an exponential model of pollen
      carryover suggests that high nectar alkaloids could benefit plants via increased
      pollen export (an estimate of male function), but only when pollinators were
      efficient and abundant and plants had large floral displays. Results suggest that
      high nectar alkaloids may benefit plants via increased pollen export under a
      restricted set of ecological conditions, but in general, the costs of high nectar
      alkaloids in reducing pollination balanced or outweighed the benefits of reducing
      self-pollen transfer for estimates of female and male reproduction.

PMID- 18724732
TI  - Seed dispersal of desert annuals.
AB  - We quantified seed dispersal in a guild of Sonoran Desert winter desert annuals
      at a protected natural field site in Tucson, Arizona, USA. Seed production was
      suppressed under shrub canopies, in the open areas between shrubs, or both by
      applying an herbicide prior to seed set in large, randomly assigned removal plots
      (10-30 m diameter). Seedlings were censused along transects crossing the
      reproductive suppression borders shortly after germination. Dispersal kernels
      were estimated for Pectocarya recurvata and Schismus barbatus from the change in
      seedling densities with distance from these borders via inverse modeling.
      Estimated dispersal distances were short, with most seeds traveling less than a
      meter. The adhesive seeds of P. recurvata went farther than the small S. barbatus
      seeds, which have no obvious dispersal adaptation. Seeds dispersed farther
      downslope than upslope and farther when dispersing into open areas than when
      dispersing into shrubs. Dispersal distances were short relative to the pattern of
      spatial heterogeneity created by the shrub and open space mosaic. This suggests
      that dispersal could contribute to local population buildup, possibly
      facilitating species coexistence. Overall, these results support the hypothesis
      that escape in time via delayed germination is likely to be more important for
      desert annuals than escape in space.

PMID- 18724733
TI  - Savanna tree density, herbivores, and the herbaceous community: bottom-up vs. top
      down effects.
AB  - Herbivores choose their habitats both to maximize forage intake and to minimize
      their risk of predation. For African savanna herbivores, the available habitats
      range in woody cover from open areas with few trees to dense, almost-closed
      woodlands. This variation in woody cover or density can have a number of
      consequences for herbaceous species composition, cover, and productivity, as well
      as for ease of predator detection and avoidance. Here, we consider two
      alternative possibilities: first, that tree density affects the herbaceous
      vegetation, with concomitant "bottom-up" effects on herbivore habitat
      preferences; or, second, that tree density affects predator visibility, mediating
      "top-down" effects of predators on herbivore habitat preferences. We sampled
      sites spanning a 10-fold range of tree densities in an Acacia drepanolobium
      dominated savanna in Laikipia, Kenya, for variation in (1) herbaceous cover,
      composition, and species richness; (2) wild and domestic herbivore use; and (3)
      degree of visibility obstruction by the tree layer. We then used structural
      equation modeling to consider the potential influences that tree density may have
      on herbivores and herbaceous community properties. Tree density was associated
      with substantial variation in herbaceous species composition and richness. Cattle
      exhibited a fairly uniform use of the landscape, whereas wild herbivores, with
      the exception of elephants, exhibited a strong preference for areas of low tree
      density. Model results suggest that this was not a response to variation in
      herbaceous-community characteristics, but rather a response to the greater
      visibility associated with more open places. Elephants, in contrast, preferred
      areas with higher densities of trees, apparently because of greater forage
      availability. These results suggest that, for all but the largest species, top
      down behavioral effects of predator avoidance on herbivores are mediated by tree
      density. This, in turn, appears to have cascading effects on the herbaceous
      vegetation. These results shed light on one of the major features of the
      "landscape of fear" in which African savanna herbivores exist.

PMID- 18724734
TI  - Interactions between macroparasites and microparasites drive infection patterns
      in free-ranging African buffalo.
AB  - Epidemiological studies typically focus on single-parasite systems, although most
      hosts harbor multiple parasite species; thus, the potential impacts of co
      infection on disease dynamics are only beginning to be recognized. Interactions
      between macroparasites, such as gastrointestinal nematodes, and microparasites
      causing diseases like TB, AIDS, and malaria are particularly interesting because
      co-infection may favor transmission and progression of these important diseases.
      Here we present evidence for strong interactions between gastrointestinal worms
      and bovine tuberculosis (TB) in free-ranging African buffalo (Syncerus caffer).
      TB and worms are negatively associated at the population, among-herd, and within
      herd scales, and this association is not solely the result of demographic
      heterogeneities in infection. Combining data from 1362 buffalo with simple
      mechanistic models, we find that both accelerated mortality of co-infected
      individuals and TB transmission heterogeneity caused by trade-offs in immunity to
      the two types of parasites likely contribute to observed infection patterns. This
      study is one of the first to examine the relevance of within-host immunological
      trade-offs for understanding parasite distribution patterns in natural
      populations.

PMID- 18724735
TI  - Parasites prevent summer breeding in white-footed mice, Peromyscus leucopus.
AB  - Food and parasites can independently play a role in destabilizing population
      fluctuations of animals, and yet, more than 50 years ago, David Lack proposed
      that these two factors should act in concert. We examined the role of these
      factors on the vital rates of free-living white-footed mice (Peromyscus leucopus)
      over the summer and autumn months. We used a replicated factorial experiment in
      which deer exclosures doubled acorn availability and anthelmintic application
      reduced gastrointestinal helminths. Specifically, we wanted to know if either
      factor or an interaction between the two accounted for the midsummer breeding
      hiatus observed in this species. We found no influence of habitat quality on
      mouse breeding, vital rates, or demography; however, anthelmintic treatment
      resulted in mice continuing to reproduce during the hiatus at the same rate as
      previously, and they also exhibited increased body condition, growth rate, and
      survival. These results provide evidence that gastrointestinal helminths reduce
      P. leucopus reproductive output in central Pennsylvania, and these effects on
      reproduction could play a role in the unstable dynamics of small mammals.

PMID- 18724736
TI  - Multiple causes of variable tick burdens on small-mammal hosts.
AB  - Blood meals by blacklegged ticks (Ixodes scapularis) on vertebrate hosts serve to
      transmit the agents of several zoonotic diseases, including Lyme disease, human
      babesiosis, and human granulocytic anaplasmosis, between host and tick. If ticks
      are aggregated on hosts, a small proportion of hosts may be responsible for most
      transmission events. Therefore, a key element in understanding and controlling
      the transmission of these pathogens is identifying the group(s) or individuals
      feeding a disproportionate number of ticks. Previous studies of tick burdens,
      however, have focused on differences in mean annual burdens between one or a few
      groups of hosts, ignoring both the strong seasonal dynamics of I. scapularis and
      their aggregation on hosts. We present a statistical modeling framework that
      predicts burdens on individual hosts throughout the year as a function of
      temporal-, site-, and individual-specific attributes, as well as the degree of
      aggregation in a negative binomial distribution. We then fit alternate versions
      of this model to an 11-year data set of I. scapularis burdens on white-footed
      mice (Peromyscus leucopus) and eastern chipmunks (Tamias striatus) to explore
      which factors are important to predicting tick burdens. We found that tick
      burdens are a complex function of many extrinsic and intrinsic factors, including
      seasonality. Specifically: (1) burdens on mice and chipmunks increased with
      densities of host-seeking ticks in a manner that suggests hosts become saturated.
      (2) Chipmunks draw larval ticks away from mice, which are efficient reservoirs of
      the Lyme disease bacterium, and mice draw nymphs away from chipmunks, which are
      key nymphal hosts. (3) While individual correlates were statistically important,
      the relationships were complex, and no group or correlate (sex, age, mass) could
      explain which hosts fed a disproportionate number of ticks. (4) Ticks were
      strongly aggregated on hosts within and across groups suggesting that some
      undiscovered quality of individual hosts was responsible for the aggregation. (5)
      Those individuals that fed more nymphs than expected, and are thus more likely to
      be infected with the Lyme disease agent, also tend to feed and infect more larvae
      than expected. Predicting which individuals those are is not yet possible.

PMID- 18724737
TI  - Habitat-mediated variation in predation risk by the American marten.
AB  - The probability of prey encounter, attack, capture, and kill are often
      hypothesized to depend on habitat structure, but field evidence in terrestrial
      systems is rare. We tested whether predation efficiency by the American marten
      (Martes americana) and fear of predation by their primary prey, the red-backed
      vole (Clethrionomys gapperi), differed between 20- to 50-year-old regenerating
      forest stands and older uncut stands. Our results showed that the frequency of
      prey encounter, prey attack, and prey kill were higher in old uncut forests,
      despite the fact that small-mammal density was similar to that in younger logged
      forests. These differences in predation efficiency were linked to higher
      abundance of coarse woody debris, which seems to offer sensory cues to martens,
      thereby increasing the odds of hunting success. Red-backed voles in regenerating
      forest stands exhibited increased wariness compared to voles living in old uncut
      forest, suggestive of a behavioral response to habitat-mediated variation in
      predation risk.

PMID- 18724738
TI  - A hierarchical model for spatial capture-recapture data.
AB  - Estimating density is a fundamental objective of many animal population studies.
      Application of methods for estimating population size from ostensibly closed
      populations is widespread, but ineffective for estimating absolute density
      because most populations are subject to short-term movements or so-called
      temporary emigration. This phenomenon invalidates the resulting estimates because
      the effective sample area is unknown. A number of methods involving the
      adjustment of estimates based on heuristic considerations are in widespread use.
      In this paper, a hierarchical model of spatially indexed capture-recapture data
      is proposed for sampling based on area searches of spatial sample units subject
      to uniform sampling intensity. The hierarchical model contains explicit models
      for the distribution of individuals and their movements, in addition to an
      observation model that is conditional on the location of individuals during
      sampling. Bayesian analysis of the hierarchical model is achieved by the use of
      data augmentation, which allows for a straightforward implementation in the
      freely available software WinBUGS. We present results of a simulation study that
      was carried out to evaluate the operating characteristics of the Bayesian
      estimator under variable densities and movement patterns of individuals. An
      application of the model is presented for survey data on the flat-tailed horned
      lizard (Phrynosoma mcallii) in Arizona, USA.

PMID- 18724739
TI  - New multidimensional functional diversity indices for a multifaceted framework in
      functional ecology.
AB  - Functional diversity is increasingly identified as an important driver of
      ecosystem functioning. Various indices have been proposed to measure the
      functional diversity of a community, but there is still no consensus on which are
      most suitable. Indeed, none of the existing indices meets all the criteria
      required for general use. The main criteria are that they must be designed to
      deal with several traits, take into account abundances, and measure all the
      facets of functional diversity. Here we propose three indices to quantify each
      facet of functional diversity for a community with species distributed in a
      multidimensional functional space: functional richness (volume of the functional
      space occupied by the community), functional evenness (regularity of the
      distribution of abundance in this volume), and functional divergence (divergence
      in the distribution of abundance in this volume). Functional richness is
      estimated using the existing convex hull volume index. The new functional
      evenness index is based on the minimum spanning tree which links all the species
      in the multidimensional functional space. Then this new index quantifies the
      regularity with which species abundances are distributed along the spanning tree.
      Functional divergence is measured using a novel index which quantifies how
      species diverge in their distances (weighted by their abundance) from the center
      of gravity in the functional space. We show that none of the indices meets all
      the criteria required for a functional diversity index, but instead we show that
      the set of three complementary indices meets these criteria. Through simulations
      of artificial data sets, we demonstrate that functional divergence and functional
      evenness are independent of species richness and that the three functional
      diversity indices are independent of each other. Overall, our study suggests that
      decomposition of functional diversity into its three primary components provides
      a meaningful framework for its quantification and for the classification of
      existing functional diversity indices. This decomposition has the potential to
      shed light on the role of biodiversity on ecosystem functioning and on the
      influence of biotic and abiotic filters on the structure of species communities.
      Finally, we propose a general framework for applying these three functional
      diversity indices.

PMID- 18724740
TI  - Distinguishing stressors acting on land bird communities in an urbanizing
      environment.
AB  - Urbanization has profound influences on ecological communities, but our
      understanding of causal mechanisms is limited by a lack of attention to its
      component stressors. Published research suggests that at landscape scales,
      habitat loss and fragmentation are the major drivers of community change, whereas
      at local scales, human activity and vegetation management are the primary
      stressors. Little research has focused on whether urbanization stressors may
      supplant natural factors as dominant forces structuring communities. We used
      model selection to determine the relative importance of urban development, human
      activity, local and landscape vegetation, topography, and geographical location
      in explaining land bird species richness, abundance, and dominance. We analyzed
      the entire community and groups of species based on ecological characteristics,
      using data collected in remnant forests along a gradient of urban development in
      the Lake Tahoe basin, California and Nevada, USA. Urbanization stressors were
      consistently among the principal forces structuring the land bird community.
      Strikingly, disturbance from human activity was the most important factor for
      richness in many cases, surpassing even habitat loss from development. Landscape
      scale factors were consistently more important than local-scale factors for
      abundance. In demonstrating considerable changes in land bird community
      structure, our results suggest that ecosystem function in urban areas may be
      severely compromised. Such changes compel local- and landscape-scale management,
      focused research, and long-term monitoring to retain biodiversity in urban areas
      to the extent possible.

PMID- 18724741
TI  - Sex-specific effects of albumen removal and nest environment manipulation on Barn
      Swallow nestlings.
AB  - In avian species, maternal provisioning to the eggs is predicted to be more
      valuable for the offspring under adverse environmental conditions and intense
      sibling competition. However, studies manipulating both the amount of maternal
      pre-hatching resources and the harshness of post-hatching environment have seldom
      been performed to date. In this experimental study of Barn Swallow (Hirundo
      rustica) nestlings, we tested the consequences of a reduction in the albumen
      content of the eggs for fitness-related offspring traits, while performing an
      unbalanced partial cross-fostering soon after hatching, either increasing or
      decreasing brood size by one nestling. By molecular sexing of the chicks, we
      additionally tested for sex-specific sensitivity of individual nestlings to
      experimental treatments and to sex ratio variation in nestmates. We predicted
      that chicks hatching from albumen-deprived eggs should suffer more than control
      chicks from the harsher rearing conditions of enlarged broods. However, although
      albumen removal depressed chick body mass, chicks hatching from control eggs did
      not fare better than those hatching from eggs with reduced albumen content in
      enlarged vs. reduced broods. Albumen removal had sex-specific effects on
      immunity, with males, but not females, hatching from eggs with reduced albumen
      content showing a lower T-cell-mediated immune response than controls, suggesting
      that the two sexes were differentially susceptible to resource deprivation during
      early ontogeny. In addition, both immune response and chick body mass at age 7
      days, when maximum growth rate is attained, declined with an increasing
      proportion of male nestmates. The effect of brood size manipulation on chick body
      mass at age 12 days, when peak body mass is attained, was also found to depend on
      brood sex composition, in that an increase in the proportion of male nestmates
      depressed offspring body mass in reduced broods, while the reverse was true in
      enlarged broods. On the whole, these findings suggest that sex differences may
      exist in environmental sensitivity and patterns of resource allocation among
      different body functions, and that brood size variation and sex composition may
      affect offspring fitness-related traits.

PMID- 18724742
TI  - An unusual trophic subsidy and species dominance in a tropical stream.
AB  - In classical theory, species are assumed to achieve dominance through competitive
      exclusion, but if food resources are limiting, cross-habitat trophic subsidies
      could also underpin dominance. The impact of dominant species on community
      dynamics may depend on the energy base of population size. We report on an
      unusual, spatially subsidized population of a tropical, stream-dwelling crab that
      dominates the benthic fauna of a Kenyan stream. Diet and stable isotope analyses
      indicated that this crab is a true omnivore, with terrestrial subsidies
      dominating both plant and animal resources. Unusually, the animal prey included
      almost no aquatic invertebrates. Instead, a single species of ant constituted
      approximately 35% of the annual diet (stomach contents analysis) and up to 90% of
      assimilated nitrogen (estimates from stable isotope analysis). Ants may be
      pivotal to enabling crab dominance, and this crab may be largely disconnected
      from the local trophic network for its dietary needs. The paucity of other
      invertebrates in the stream community suggests that this super-dominant crab is a
      strong interactor that suppresses aquatic invertebrate populations. Common
      stabilizing attributes of spatially subsidized food webs (e.g., asynchronous prey
      availability, wide feeding niche, consumer migration) were absent from this
      system, and although apparently stable, it may be vulnerable to disturbance in
      the donor habitat.

PMID- 18724743
TI  - Fish distributions and nutrient cycling in streams: can fish create
      biogeochemical hotspots?
AB  - Rates of biogeochemical processes often vary widely in space and time, and
      characterizing this variation is critical for understanding ecosystem
      functioning. In streams, spatial hotspots of nutrient transformations are
      generally attributed to physical and microbial processes. Here we examine the
      potential for heterogeneous distributions of fish to generate hotspots of
      nutrient recycling. We measured nitrogen (N) and phosphorus (P) excretion rates
      of 47 species of fish in an N-limited Neotropical stream, and we combined these
      data with population densities in each of 49 stream channel units to estimate
      unit- and reach-scale nutrient recycling. Species varied widely in rates of N and
      P excretion as well as excreted N:P ratios (6-176 molar). At the reach scale,
      fish excretion could meet >75% of ecosystem demand for dissolved inorganic N and
      turn over the ambient NH4 pool in <0.3 km. Areal N excretion estimates varied 47
      fold among channel units, suggesting that fish distributions could influence
      local N availability. P excretion rates varied 14-fold among units but were low
      relative to ambient concentrations. Spatial variation in aggregate nutrient
      excretion by fish reflected the effects of habitat characteristics (depth, water
      velocity) on community structure (body size, density, species composition), and
      the preference of large-bodied species for deep runs was particularly important.
      We conclude that the spatial distribution of fish could indeed create hotspots of
      nutrient recycling during the dry season in this species-rich tropical stream.
      The prevalence of patchy distributions of stream fish and invertebrates suggests
      that hotspots of consumer nutrient recycling may often occur in stream
      ecosystems.

PMID- 18724744
TI  - How many animals really do the Levy walk? Comment.

PMID- 18724745
TI  - Can stable isotope ratios provide for community-wide measures of trophic
      structure? Comment.

PMID- 18724746
TI  - Microbial quality of raw aquacultured fish fillets procured from Internet and
      local retail markets.
AB  - The microbial quality of raw fillets of aquacultured catfish, salmon, tilapia,
      and trout was evaluated. A total of 272 fillets from nine local and nine Internet
      retail markets were tested. Mean values were 5.7 log CFU/g for total aerobic
      mesophiles, 6.3 log CFU/g for psychrotrophs, and 1.9 log most probable number
      (MPN) per gram for coliforms. Differences in these microbial levels between the
      two kinds of markets and among the four types of fish were not significant (P >
      0.05), except that Internet trout fillets had about 0.8-log higher aerobic
      mesophiles than did trout fillets purchased locally. Although Escherichia coli
      was detected in 1.4, 1.5, and 5.9% of trout, salmon, and tilapia, respectively,
      no sample had > or = 1.0 log MPN/g. However, E. coli was found in 13.2% of
      catfish, with an average of 1.7 log MPN/g. About 27% of all fillets had Listeria
      spp., and a positive correlation between the prevalence of Listeria spp. and
      Listeria monocytogenes was observed. Internet fillets had a higher prevalence of
      both Listeria spp. and L. monocytogenes than did those fillets purchased locally.
      L. monocytogenes was present in 23.5% of catfish but in only 5.7, 10.3, and 10.6%
      of trout, tilapia, and salmon, respectively. Salmonella and E. coli O157 were not
      found in any sample. A follow-up investigation using catfish operation as a model
      revealed that gut waste exposed during evisceration is a potential source of
      coliforms and Listeria spp.

PMID- 18724747
TI  - Survival of Listeria monocytogenes strains in a dry sausage model.
AB  - The survival of five inoculated Listeria monocytogenes strains (DCS 31, DCS 184,
      AT3E, HT4E, and HR5E) was studied in dry fermented sausages prepared using two
      different starter cultures (starter A and B) with or without a protective
      Lactobacillus plantarum DDEN 2205 strain. L. monocytogenes was detected
      throughout ripening in every sausage sample in which the L. plantarum DDEN 2205
      strain had not been used. The use of either starter A, with a high concentration
      of protective culture, or starter B, with a low concentration of protective
      culture, resulted in L. monocytogenes-negative sausages after 17 days of
      ripening. Differential survival was noted among the L. monocytogenes strains
      during fermentation. Strains AT3E and DCS 31 survived in sausages with protective
      cultures more often than did the other strains, whereas HT4E and HR5E were
      inhibited during ripening by all starter and protective cultures used. Protective
      cultures such as L. plantarum may be used as part of a hurdle strategy in dry
      sausage processing, but variations in susceptibility of different L.
      monocytogenes strains can create problems if other hurdles are not included.

PMID- 18724748
TI  - Comparison of the stress response of Listeria monocytogenes strains with sprout
      colonization.
AB  - Twenty-nine strains of the foodborne pathogen Listeria monocytogenes were tested
      for their ability to colonize alfalfa, radish, and broccoli sprouts and their
      capacity to withstand acid and oxidative stress, two stresses common to the
      sprouting environment. Wide variation in the ability of different strains to
      colonize alfalfa sprouts were confirmed, but the variations among radish and
      broccoli sprouts were not as large. With a few exceptions, strains that were poor
      colonizers of alfalfa tended to be among the poorer colonizers of radish and
      broccoli and vice versa. The strains also were variable in their resistance to
      both acid and oxidative stress. Statistical analysis revealed no correlation
      between acid stress and sprout colonization, but there was a positive correlation
      between resistance to oxidative stress and colonization of all three sprout
      types. Although the response to oxidative stress is important for L.
      monocytogenes virulence, it also may be important for life outside of a host.

PMID- 18724749
TI  - 60-day aging requirement does not ensure safety of surface-mold-ripened soft
      cheeses manufactured from raw or pasteurized milk when Listeria monocytogenes is
      introduced as a postprocessing contaminant.
AB  - Because of renewed interest in specialty cheeses, artisan and farmstead producers
      are manufacturing surface-mold-ripened soft cheeses from raw milk, using the 60
      day holding standard (21 CFR 133.182) to achieve safety. This study compared the
      growth potential of Listeria monocytogenes on cheeses manufactured from raw or
      pasteurized milk and held for > 60 days at 4 degrees C. Final cheeses were within
      federal standards of identity for soft ripened cheese, with low moisture targets
      to facilitate the holding period. Wheels were surface inoculated with a five
      strain cocktail of L. monocytogenes at approximately 0.2 CFU/ cm2 (low level) or
      2 CFU/cm2 (high level), ripened, wrapped, and held at 4 degrees C. Listeria
      populations began to increase by day 28 for all treatments after initial
      population declines. From the low initial inoculation level, populations in raw
      and pasteurized milk cheese reached maximums of 2.96 +/- 2.79 and 2.33 +/- 2.10
      log CFU/g, respectively, after 60 days of holding. Similar growth was observed in
      cheese inoculated at high levels, where populations reached 4.55 +/- 4.33 and
      5.29 +/- 5.11 log CFU/g for raw and pasteurized milk cheeses, respectively. No
      significant differences (P < 0.05) were observed in pH development, growth rate,
      or population levels between cheeses made from the different milk types.
      Independent of the milk type, cheeses held for 60 days supported growth from very
      low initial levels of L. monocytogenes introduced as a postprocess contaminant.
      The safety of cheeses of this type must be achieved through control strategies
      other than aging, and thus revision of current federal regulations is warranted.

PMID- 18724750
TI  - Survival and growth of acid-adapted and unadapted Salmonella in and on raw
      tomatoes as affected by variety, stage of ripeness, and storage temperature.
AB  - Consumption of raw round and Roma tomatoes has been associated with outbreaks of
      salmonellosis. A study was done to determine whether survival and growth of
      Salmonella in and on tomatoes is affected by variety of tomato, stage of
      ripeness, and storage temperature. The influence of acid adaptation of cells and
      site of inoculation on survival and growth was studied. Salmonella grew in stem
      scar and pulp tissues of round, Roma, and grape tomatoes stored at 12 and 21
      degrees C but not in those tomatoes stored at 4 degrees C. Survival and growth
      was largely unaffected by variety and stage of ripeness at the time of
      inoculation. The pathogen did not grow on the skin of grape tomatoes stored at 4,
      12, and 21 degrees C. Survival and growth of Salmonella inoculated into stem scar
      and pulp tissues of round and Roma tomatoes were unaffected by exposure of cells
      to an acidic (pH 4.75) environment before inoculation. Results emphasize the
      importance of preventing contamination of tomatoes with Salmonella at all stages
      of ripeness, regardless of variety or previous exposure of cells to an acidic
      environment.

PMID- 18724751
TI  - Low incidence of foodborne pathogens of concern in raw milk utilized for
      farmstead cheese production.
AB  - Overall milk quality and prevalence of four target pathogens in raw milk destined
      for farmstead cheesemaking was examined. Raw milk samples were collected weekly
      from June to September 2006 from 11 farmstead cheese operations manufacturing raw
      milk cheese from cow's, goat's, and sheep's milk. Samples were screened for
      Listeria monocytogenes, Staphylococcus aureus, Salmonella, and Escherichia coli
      O157:H7 both quantitatively (direct plating) and qualitatively (PCR). Overall,
      96.8% of samples had standard plate counts of < 100,000 CFU/ml, 42.7% of which
      were < 1,000 CFU/ml. Although no federal standards exist for coliforms in raw
      milk, 61% of samples tested conformed to pasteurized milk standards under the
      U.S. Pasteurized Milk Ordinance (PMO) at < 10 CFU/ml. All cow and sheep milk
      samples and 93.8% of goat milk samples were within the limits dictated by the PMO
      for somatic cell counts. Of the 11 farms, 8 (73%) produced samples that were
      positive for S. aureus, which was detected in 34.6% (46 of 133) of milk samples.
      L. monocytogenes was isolated from three milk samples (2.3%), two of which were
      from the same farm. E. coli O157:H7 was recovered from one sample of goat's milk
      for an overall incidence of 0.75%. Salmonella was not recovered from any of the
      133 samples. The findings of this study suggest that most raw milk intended for
      farmstead cheesemaking is of high microbiological quality with a low incidence of
      pathogens. These data will help inform risk assessments associated with the
      microbiological safety of farmstead cheeses, particularly those manufactured from
      raw milk.

PMID- 18724752
TI  - Survival and transfer of murine norovirus 1, a surrogate for human noroviruses,
      during the production process of deep-frozen onions and spinach.
AB  - The reduction of murine norovirus 1 (MNV-1) on onions and spinach by washing was
      investigated as was the risk of contamination during the washing procedure. To
      decontaminate wash water, the industrial sanitizer peracetic acid (PAA) was added
      to the water, and the survival of MNV-1 was determined. In contrast to onions,
      spinach undergoes a heat treatment before freezing. Therefore, the resistance of
      MNV-1 to blanching of spinach was examined. MNV-1 genomic copies were detected
      with a real-time reverse transcription PCR assay in PAA-treated water and
      blanched spinach, and PFUs (representing infectious MNV-1 units) were determined
      with a plaque assay. A < or = 1-log reduction in MNV-1 PFUs was achieved by
      washing onion bulbs and spinach leaves. More than 3 log PFU of MNV-1 was
      transmitted to onion bulbs and spinach leaves when these vegetables were washed
      in water containing approximately 5 log PFU/ml. No decline of MNV-1 occurred in
      used industrial spinach wash water after 6 days at room temperature. A
      concentration of 20 ppm of PAA in demineralized water (pH 4.13) and in potable
      water (pH 7.70) resulted in reductions of 2.88 +/- 0.25 and 2.41 +/- 0.18 log
      PFU, respectively, after 5 min of exposure, but no decrease in number of genomic
      copies was observed. No reduction of MNV-1 PFUs was observed on frozen onions or
      spinach during storage for 6 months. Blanching spinach (80 degrees C for 1 min)
      resulted in at least 2.44-log reductions of infectious MNV-1, but many genomic
      copies were still present.

PMID- 18724753
TI  - Aqueous matrix compositions and pH influence feline calicivirus inactivation by
      high pressure processing.
AB  - The individual effects of pH (pH 3 to 8), NaCl (0 to 21%), sucrose (0 to 70%),
      and whey protein (0 to 2%) on pressure resistance of feline calicivirus (FCV) in
      Dulbecco's modified Eagle medium with 10% fetal bovine serum were determined. At
      pH 3 through 8, the virus was more resistant to pressure at a pH of < or = 5.2.
      For FCV samples with sucrose (up to 40%) or NaCl (up to 12%), the amount of FCV
      inactivated by pressure was inversely proportional to the sucrose or NaCl
      concentration. For example, a treatment of 250 MPa at 20 degrees C for 5 min
      reduced the FCV titer by 5.1 log PFU/ml without added sucrose and by 0.9 log
      PFU/ml with 40% sucrose. Reduced pressure sensitivity with increasing NaCl and
      sucrose concentrations was not a simple function of water activity. Different PFU
      reductions were observed for NaCl and sucrose samples with equivalent water
      activity. When protein at concentrations up to 2% did not provide a protective
      effect. The combined effect of NaCl and sucrose at 4 and 20 degrees C on pressure
      resistance of FCV also was examined. When both NaCl and sucrose were added to the
      FCV stock, they had an additive effect on increasing the pressure resistance of
      FCV. The individual (6% NaCl or 20% sucrose) and combined (6% NaCl plus 20%
      sucrose) resistance effects did not abrogate enhanced inactivation for pressure
      treatments at 4 degrees C compared with those at 20 degrees C. Aqueous matrix
      compositions, in particular different concentrations of NaCl and sucrose or
      different pH values, can substantially alter the efficiency of virus inactivation
      by high pressure processing.

PMID- 18724754
TI  - Carvacrol and cinnamaldehyde facilitate thermal destruction of Escherichia coli
      O157:H7 in raw ground beef.
AB  - The heat resistance of a four-strain mixture of Escherichia coli O157:H7 in raw
      ground beef in both the absence and presence of the antimicrobials carvacrol and
      cinnamaldehyde was tested at temperatures ranging from 55 to 62.5 degrees C.
      Inoculated meat packaged in bags was completely immersed in a circulating water
      bath, cooked for 1 h to an internal temperature of 55, 58, 60, or 62.5 degrees C,
      and then held for predetermined lengths of time ranging from 210 min at 55
      degrees C to 5 min at 62.5 degrees C. The surviving bacteria were enumerated by
      spiral plating onto tryptic soy agar overlaid with sorbitol MacConkey agar.
      Inactivation kinetics of the pathogens deviated from first-order kinetics. D
      values (time for the bacteria to decrease by 90%) in the control beef ranged from
      63.90 min at 55 degrees C to 1.79 min at 62.5 degrees C. D-values determined by a
      logistic model ranged from 43.18 min (D1, the D-value of a major population of
      surviving cells) and 89.84 min (D2, the D-value of a minor subpopulation) at 55
      degrees C to 1.77 (D1) and 0.78 min (D2) at 62.5 degrees C. The thermal death
      times suggested that to achieve a 4-D reduction, contaminated processed ground
      beef should be heated to an internal temperature of 60 degrees C for at least
      30.32 min. Significantly increased sensitivity to heat (P < 0.05) was observed
      with the addition and/or increasing levels of carvacrol or cinnamaldehyde from
      0.5 to 1.0%. The observed thermal death times may facilitate the design of
      acceptance limits at critical control points for ground beef at lower times and
      temperatures of heating.

PMID- 18724755
TI  - Effects of high pressure, subzero temperature, and pH on survival of Listeria
      monocytogenes in buffer and smoked salmon.
AB  - High pressure processing is a novel food preservation technology, applied for
      over 15 years in the food industry to inactivate spoilage and pathogenic
      microorganisms. Many studies have shown the differential resistance of bacterial
      cells to high pressure. Listeria monocytogenes is a bacterium able to grow at
      refrigerated temperature and to survive for a long time in minimally processed
      foods such as raw smoked fish. The freezing process does not cause significant
      decline of L. monocytogenes. The phase diagram of water under pressure permits a
      pressure treatment under subzero temperature, without the disadvantages of
      freezing for food quality. The aim of this study was to estimate if combined
      effects of pressure and subzero temperature could increase the destruction of L.
      monocytogenes in buffer and in smoked salmon. We investigated effects of high
      pressure processing (100, 150, and 200 MPa) combined with subzero temperatures (
      10, -14, and -18 degrees C) and pH (7.0 and 4.5). Results showed that the most
      effective high-pressure treatment to inactivate L. monocytogenes was 200 MPa, -18
      degrees C, and pH 4.5. The relevance of pressure holding time and the synergistic
      effect of pressure coupled with the subzero temperature to inactivate bacteria
      are highlighted. Modifications of physical properties (color and texture) were a
      lightening of color and an increase of toughness, which might be accepted by
      consumers, since safety is increased.

PMID- 18724756
TI  - Cold atmospheric plasma disinfection of cut fruit surfaces contaminated with
      migrating microorganisms.
AB  - The efficacy of cold atmospheric gas plasmas against Escherichia coli type 1,
      Saccharomyces cerevisiae, Gluconobacter liquefaciens, and Listeria monocytogenes
      Scott A was examined on inoculated membrane filters and inoculated fruit
      surfaces. Inoculated samples were exposed to a cold atmospheric plasma plume
      generated by an AC voltage of 8 kV at 30 kHz. The cold atmospheric plasma used in
      this study was very efficient in reducing the microbial load on the surfaces of
      filter membranes. However, its efficacy was markedly reduced for microorganisms
      on the cut surfaces. This lack of effect was not the result of quenching of
      reactive plasma species responsible for microbial inactivation but principally
      the result of the migration of microorganisms from the exterior of the fruit
      tissue to its interior. The velocity of migration through melon tissues was
      estimated to be around 300 microm min(-1) for E. coli and S. cerevisiae and
      through mango tissues to be 75 to 150 microm min(-1). These data can serve as
      operational targets for optimizing the performance of gas plasma inactivation
      processes. The current capabilities of cold atmospheric plasmas are reviewed and
      ways to improve their bactericidal efficacy are identified and discussed.
      Considerable scope exists to enhance significantly the efficacy of cold
      atmospheric plasmas for decontaminating fresh cut fruits.

PMID- 18724757
TI  - Effects of potassium sorbate on postharvest brown rot of stone fruit.
AB  - The effect of potassium sorbate (K-sorb), a low-toxicity chemical, to control
      Monilinia spp. was investigated. Preliminary in vitro studies found the MIC of K
      sorb for conidial germination and mycelial growth was, respectively, 260 and
      1,250 mg/ liter. Immersion of naturally infected peach and nectarine fruit in a
      solution (15 g/liter) of K-sorb for 120 s reduced brown rot by over 80% in four
      of five trials. Although treated fruits showed a significant reduction in
      firmness with respect to the control, they did not reach the overripe stage and
      retained acceptable quality parameters. In an attempt to elucidate the mechanism
      of action for K-sorb, the inhibition of enzymatic activity by K-sorb was also
      tested. In a radial diffusion assay, the addition of K-sorb to agarose reduced
      polygalacturonase (PG) activity across the concentrations considered. The
      greatest reduction (54.3%, with respect to the control) was obtained at a sorbate
      concentration of 15 g/liter. PG kinetic activity of Monilinia laxa observed by a
      spectrophotometric assay peaked after 40 min in all samples tested. PG activity
      was significantly higher in the control than in the samples with increased K-sorb
      concentrations. In conclusion, based on these findings, K-sorb can be recommended
      as a low-toxicity antifungal compound against Monilinia spp. in peaches and
      nectarines with its mode of action probably depending in part on the inhibition
      of PG activity in M. laxa.

PMID- 18724758
TI  - Standardized inspections of food premises during the 2004 Athens Olympic Games:
      descriptive analysis and risk factors for unsatisfactory results.
AB  - Standardized inspections of food premises are part of environmental health
      systems implemented worldwide. The food safety strategy for the 2004 Olympic
      Games included standardized inspections to ensure uniformity and consistency of
      procedures and effective electronic management of data. Inspections were carried
      out by 196 inspectors in the five Olympic cities: Athens, Thessalonica, Volos,
      Iraklio, and Patra. From January 2003 to September 2004, a total of 1,249 food
      premises were inspected. An unsatisfactory inspection result (C grade) was
      received by 347 (27.8%) food premises, a relatively satisfactory result (B grade)
      was received by 332 (26.6%), and a satisfactory result (A grade) was received by
      570 (45.6%). About 16% of inspected premises did not hold a valid permit.
      Unsatisfactory inspection results were more frequent for premises located in the
      two largest Greek cities in comparison with the other smaller cities (relative
      risk = 1.95, 95% confidence interval [CI] = 1.36 to 2.80). Based on logistic
      regression analysis, unsatisfactory inspection results were positively associated
      with food premises that were not located on a ground floor (odds ratio [OR] =
      2.56, 95% CI = 1.39 to 4.73) and negatively associated with application of hazard
      analysis critical control point (HACCP) principles (OR = 0.27, 95% CI = 0.10 to
      0.71). Food hygiene education through formal training programs should be
      encouraged to improve compliance of food premises. Food premises located on hotel
      floors and serving buffet meals are at higher risk for unsatisfactory conditions.
      Businesses that implemented a HACCP system within their operations to ensure food
      safety operated under more hygienic conditions. Future inspections by Public
      Health Authorities should involve elements of audit after the legislation for the
      application of HACCP principles.

PMID- 18724759
TI  - Hand washing frequencies and procedures used in retail food services.
AB  - Transmission of viruses, bacteria, and parasites to food by way of improperly
      washed hands is a major contributing factor in the spread of foodborne illnesses.
      Field observers have assessed compliance with hand washing regulations, yet few
      studies have included consideration of frequency and methods used by sectors of
      the food service industry or have included benchmarks for hand washing. Five 3-h
      observation periods of employee (n = 80) hand washing behaviors during menu
      production, service, and cleaning were conducted in 16 food service operations
      for a total of 240 h of direct observation. Four operations from each of four
      sectors of the retail food service industry participated in the study: assisted
      living for the elderly, childcare, restaurants, and schools. A validated
      observation form, based on 2005 Food Code guidelines, was used by two trained
      researchers. Researchers noted when hands should have been washed, when hands
      were washed, and how hands were washed. Overall compliance with Food Code
      recommendations for frequency during production, service, and cleaning phases
      ranged from 5% in restaurants to 33% in assisted living facilities. Procedural
      compliance rates also were low. Proposed benchmarks for the number of times hand
      washing should occur by each employee for each sector of food service during each
      phase of operation are seven times per hour for assisted living, nine times per
      hour for childcare, 29 times per hour for restaurants, and 11 times per hour for
      schools. These benchmarks are high, especially for restaurant employees.
      Implementation would mean lost productivity and potential for dermatitis; thus,
      active managerial control over work assignments is needed. These benchmarks can
      be used for training and to guide employee hand washing behaviors.

PMID- 18724760
TI  - Food safety knowledge and behaviors of women, infant, and children (WIC) program
      participants in the United States.
AB  - Although the incidence of foodborne illnesses has declined, thousands of cases
      are still reported in the United States. In conjunction with industry efforts to
      reduce foodborne pathogens, consumers play an important role in decreasing
      foodborne illnesses. To assess food safety knowledge and food handling behaviors
      of low-income, high-risk populations, a study was conducted with participants of
      the Special Supplemental Food Program for Women, Infants, and Children (WIC). A
      survey was conducted with 1,598 clients from 87 WIC agencies nationwide.
      Descriptive statistics, chi-square analyses, t tests, and analyses of variance
      were calculated. A majority of respondents received food safety information from
      WIC (78.7%), family (63.1%), and television (60.7%). Most respondents recognized
      the necessity for washing and sanitizing cutting boards and utensils (94.3%), but
      only 66.1% knew the correct ways to sanitize. Using a thermometer to ensure
      doneness of meat was least recognized (23.7%) and used by even fewer respondents
      (7.7%). The majority (77.4%) used color of meat and/or juices when checking the
      doneness of ground beef items. Over half of the respondents (58.4%) used
      acceptable thawing methods, but many thawed frozen meats on the counter (21.0%)
      or in a sink filled with water (20.6%). There were significant differences in
      thawing methods, overall knowledge scores, and overall behavior scores among
      different racial and ethnic groups. White respondents had higher knowledge scores
      than did Hispanics, and blacks had lower behavior scores than did individuals in
      the other racial and ethnic groups. Results of the study suggested the need for
      food safety education for low-income consumers and different messages to be
      delivered to specific demographic groups.

PMID- 18724761
TI  - Operational practices associated with foodborne disease outbreaks in the catering
      industry in England and Wales.
AB  - Catering businesses continue to be the most common setting for foodborne disease
      outbreaks. In a study of catering businesses in England and Wales, operational
      practices relating to the supply, preparation, and service of food in 88
      businesses associated with outbreaks were compared with those practices at 88
      control businesses. Operational practices did not differ significantly between
      case and control businesses but larger small medium-size enterprise (SME)
      businesses were more likely to be associated with foodborne disease outbreaks
      than were micro-SME businesses. Businesses associated with outbreaks of
      Salmonella infection were less likely to use local or national suppliers but
      instead used regional suppliers, especially for eggs. This practice was the only
      significantly independent operational practice associated with outbreaks of
      Salmonella infection. Regional egg suppliers also were more likely to be used by
      businesses associated with outbreaks attributed to food vehicles containing eggs.
      Businesses associated with egg-associated outbreaks were less likely to use eggs
      produced under an approved quality assurance scheme, suggesting that the
      underlying risk associated with using regional suppliers may relate to the use of
      contaminated eggs.

PMID- 18724762
TI  - Discovery and development of educational strategies to encourage safe food
      handling behaviors in cancer patients.
AB  - Foodborne infections pose a threat to cancer patients who are immunocompromised
      because of disease or medical therapy. Comprehensive food safety education can
      raise cancer patients' awareness of risk for foodborne infections and encourage
      risk-reducing behavior. The objectives of this study were to assess food safety
      informational needs of cancer patients and to determine factors that may
      influence prospective educational interventions that foster risk-reducing
      behaviors. Focus groups with cancer patients were formed, and interviews with
      health professionals working with cancer patients were conducted. Findings were
      used to develop three educational resource prototypes for cancer patients.
      Information from two additional focus groups and interviews with cancer patients
      was used to evaluate the prototypes before revision and finalization. There was a
      general awareness among focus group participants that chemotherapy increased
      their susceptibility to foodborne illness and infections. Participants had a
      basic knowledge of safe food handling practices but did not necessarily link
      their awareness of increased susceptibility for infection with their routine food
      handling practices. When informed of specific high-risk foods, there was
      skepticism about compliance due to disbelief of the risk, personal preferences
      for the high-risk food, and lack of information about how to use the
      recommendation. Most of the health care providers agreed that food safety
      information should be provided by dietitians, physicians, and nurses, but
      physicians stated they had little time to do so. Cancer patients expressed
      positive attitudes toward the educational resource prototypes and willingness to
      follow the food safety recommendations provided.

PMID- 18724763
TI  - Comparison of Shiga-like toxin II expression between two genetically diverse
      lineages of Escherichia coli O157:H7.
AB  - The existence of two separate lineages of Escherichia coli O157:H7 has previously
      been reported, and research indicates that one of these lineages (lineage I)
      might be more pathogenic toward human hosts. We postulated that the lineage more
      pathogenic expresses higher levels of Shiga toxin 2 (Stx2) than do the
      nonpathogenic lineage II. A comprehensive set of methodologies were used to
      investigate the difference in Stx2 protein and mRNA expression between the two
      lineages. An initial Stx2-specific enzyme-linked immunosorbent assay was
      conducted, and lineage I overall demonstrated significantly more toxin proteins
      expressed (P < 0.01). Gene expression analyses all showed significantly higher
      stx2 gene expression in lineage I (P = 0.02). PCR mapping revealed a possible
      explanation for decreased amounts of stx2 transcripts in the potentially
      nonpathogenic lineage II isolates, suggesting that genomic changes have modified
      the toxin-encoding region of the phage. This study provides additional data to
      support the existence of two diverse lineages of E. coli O157:H7, one of which
      may have lower pathogenic potential in relation to human hosts. The PCR described
      also provides a possible screening tool for E. coli O157 populations to
      differentiate these lineages. This study provides useful information on the
      ecology of E. coli O157, with broad implications within the clinical, scientific,
      and livestock industries.

PMID- 18724764
TI  - Antimicrobial resistance and association with class 1 integrons in Escherichia
      coli isolated from turkey meat products.
AB  - The objective of this study was to quantify the role of class 1 integrons in
      antimicrobial resistance in Escherichia coli isolated from turkey meat products
      purchased from retail outlets in the Midwestern United States. Of 242 E. coli
      isolates, 41.3% (102 of 242) tested positive for class 1 integrons. A significant
      association was shown between presence of class 1 integrons in E. coli isolates
      and the resistance to tetracycline, ampicillin, streptomycin, gentamicin,
      sulfisoxazole, and trimethoprim-sulfamethoxazole. Attributable risk analysis
      revealed that for every 100 E. coli isolates carrying class 1 integrons,
      resistance was demonstrated for ampicillin (22%), gentamycin (48%), streptomycin
      (29%), sulfisoxazole (40%), trimethoprim-sulfamethoxazole (7%), and tetracycline
      (26%). Non-integron-related antimicrobial resistance was demonstrated for
      ampicillin (65%), gentamycin (16.9%), streptomycin (42.1%), sulfisoxazole
      (35.8%), and tetracycline (49.7%). Population-attributable fraction analysis
      showed that class 1 integrons accounted for the following resistances:
      gentamycin, 71% (50 of 71), amoxicillin-clavulanic acid, 19.6% (6 of 33),
      nalidixic acid, 34% (7 of 21), streptomycin, 28% (30 of 107), sulfisoxazole, 38%
      (40 of 106), and tetracycline, 14%, (26 of 185). In conclusion, although class 1
      integrons have been implicated in resistance to antimicrobial agents, other non
      integron resistance mechanisms seem to play an important part.

PMID- 18724765
TI  - Prevalence and characterization of Salmonella in bovine lymph nodes potentially
      destined for use in ground beef.
AB  - A potential source of pathogenic bacteria in ground beef is the lymphatic system,
      specifically the lymph nodes. Bacteria have been isolated from the lymph nodes of
      cattle at slaughter; however, most studies have dealt with mesenteric lymph
      nodes, which are not normally incorporated into ground beef. The objective of the
      current study was to determine the prevalence and multidrug-resistance status of
      Salmonella in bovine lymph nodes associated with lean and fat trimmings that
      might be utilized in ground beef production. Bovine lymph nodes (n = 1,140) were
      collected from commercial beef processing plants. Half of the lymph nodes sampled
      were obtained from cull cow and bull processing plants, and the remainder were
      obtained from fed beef processing plants. Lymph nodes located in chuck and flank
      adipose tissue were collected for this study. Salmonella prevalence in the lymph
      node samples was low, with an overall prevalence of 1.6% and a 95% confidence
      interval of 0.85 to 2.3%. Lymph nodes from cull cattle carcasses had a higher
      prevalence of Salmonella than did those from fed cattle carcasses. Lymph nodes
      from the flanks of cow and bull carcasses had the highest prevalence at 3.86%,
      whereas lymph nodes from the chuck region of fed cattle carcasses had the lowest
      prevalence at 0.35%. Three of the 18 Salmonella-positive lymph node samples
      contained multidrug-resistant Salmonella, and all 3 samples were from cull
      cattle.

PMID- 18724766
TI  - Detection of human enteric viruses in Japanese clams.
AB  - A total of 57 clam packages that were collected from supermarkets and fish
      markets from 11 different sites in western Japan between 8 December 2005 and 6
      September 2006 were examined for human enteric viruses (i.e., norovirus, Aichi
      virus, rotavirus, adenovirus, hepatitis A virus, and astrovirus), using PCR and
      reverse transcription PCR. Sixty-one percent of the packages were contaminated
      with one type of virus, 9% had two different types of viruses, 28% had three
      different types of viruses, and 9% had at least four different types of viruses.
      Thirty-one (54%) of 57 packages were contaminated with noroviruses. Norovirus
      genogroup I and genogroup II sequences were detected in 24 and 23 packages,
      respectively, and these sequences belonged to nine genogroup I and eight
      genogroup II genotypes. Aichi viruses were found in 19 (33%) of 57 packages, and
      these belonged to genogroup A. Rotaviruses (group A) were detected in 14 (42%) of
      33 of packages and 9 of 14 rotavirus-positive packages contained two or more
      rotavirus genogroup types. Adenoviruses (Ad40 and Ad41) were detected in 17 (52%)
      of 33 packages. One of the 57 (2%) packages was positive with hepatitis A virus
      (subtype IA). Astrovirus was not detected in any of the packages. This is the
      first study to detect such a high level of contamination in Japanese clams. These
      results represent an important finding because the Japanese clams were considered
      suitable for human consumption. Further studies are needed to determine the
      health risks associated with eating these highly contaminated clams.

PMID- 18724767
TI  - Seasonal tracking of histo-blood group antigen expression and norovirus binding
      in oyster gastrointestinal cells.
AB  - Noroviruses (NORs) are the most common cause of viral gastroenteritis outbreaks.
      Outbreaks are often associated with the consumption of contaminated oysters and
      generally occur between the months of November and March, when oysters produce
      the highest levels of glycogen. Oyster glycogen has been proposed as playing a
      role in NOR accumulation. Recent research indicates that histo-blood group
      antigens (HBGAs) function as viral receptors on human gastrointestinal cells. In
      this study, oyster glycogen was tested to determine whether it contains HBGA-like
      molecules and whether it plays a role in NOR binding. The correlation between the
      amount of HBGA expression and NOR binding also was measured. We also tested
      whether seasonal changes affected HBGA expression and binding of recombinant
      NORs. The results indicate that recombinant NOR binding is highly correlated with
      HBGA expression in Virginica (Crassostrea virginica), Pacific (Crassostrea
      gigas), and Kumamato (Crassostrea sikamea) oysters, but the association does not
      have a seasonal pattern. No obvious trend in either HBGA expression or
      recombinant NOR binding by month was noted. A significant increase in recombinant
      NOR binding was observed in Virginica and Pacific oysters in a season not
      generally associated with NOR gastroenteritis outbreaks. A significant increase
      in HBGA expression also was observed for Pacific and Virginica oysters in the
      same season. Paradoxically, HBGA expression and NOR binding both were higher in
      oysters produced in the non-NOR gastroenteritis season (April through October)
      than in those produced in the NOR gastroenteritis season (November through
      March), suggesting that seasonal NOR gastroenteritis outbreaks are not associated
      with high levels of HBGA expression or NOR binding.

PMID- 18724768
TI  - Antimicrobial activity of extracts of edible wild and cultivated mushrooms
      against foodborne bacterial strains.
AB  - The antimicrobial activity of aqueous, methanol, hexane, and ethyl acetate
      extracts from edible wild and cultivated mushrooms against nine foodborne
      pathogenic bacterial strains (Escherichia coli O157:H7, Salmonella Enteritidis,
      Shigella sonnei, Vibrio parahaemolyticus, Yersinia enterocolitica, Bacillus
      cereus, Clostridium perfringens, Listeria monocytogenes, and Staphylococcus
      aureus) was screened with a disk diffusion assay. Twenty-nine of the 48 species
      tested had antimicrobial activity. Methanol, ethyl acetate, and aqueous extracts
      accounted for 92.8% of the positive assays, whereas the hexane extracts accounted
      for only 7.2%. Gram-positive bacteria were more sensitive than gram-negative
      bacteria to fungal extracts, and C. perfringens was the most sensitive
      microorganism. Aqueous extracts from Clitocybe geotropa and Lentinula edodes had
      the highest antimicrobial activity against all the bacterial strains tested.

PMID- 18724769
TI  - Bacterial flora of processed broiler chicken skin after successive washings in
      mixtures of potassium hydroxide and lauric acid.
AB  - Changes in the size of populations of different groups of bacteria composing the
      normal flora of processed broiler skin were examined after each of five
      consecutive washings in mixtures of potassium hydroxide (KOH) and lauric acid
      (LA). Portions of skin from commercially processed broiler carcasses were washed
      in distilled water (control) or in mixtures of 0.25% KOH-0.5% LA or 0.5% KOH-1%
      LA by using a stomacher laboratory blender to agitate the skin in the solutions.
      After each wash, skin was transferred to fresh solutions, and washing was
      repeated to provide samples washed one to five times in each solution. Bacteria
      in rinsates of the washed skin were enumerated on plate count (PC) agar,
      Staphylococcus (STA) agar, Levine eosin methylene blue (EMB) agar, lactic acid
      bacteria (LAB) agar, and Perfringens (PER) agar with TSC supplement. Selected
      isolates recovered on each medium were identified. Overall, no significant
      differences were observed in numbers of bacteria recovered on PC, STA, or EMB
      agars from skin after repeated washing in water, but there were significant
      reductions in the number of bacteria recovered on LAB and PER agars. Repeated
      washing of skin in 0.25% KOH-0.5% LA or 0.5% KOH-1% LA generally produced
      significant reductions in the number of bacteria recovered on all media.
      Furthermore, no bacteria were recovered on PER agar from skin washed five times
      in 0.25% KOH-0.5% LA. Likewise, no bacteria were recovered on EMB or LAB agars
      from skin washed three or more times in 0.5% KOH-1% LA or on PER agar from skin
      washed four or five times in this solution. Staphylococcus spp. were identified
      as the skin isolates with the highest degree of resistance to the bactericidal
      activity of KOH-LA. Findings indicate that although bacteria may be continually
      shed from poultry skin after repeated washings, bactericidal surfactants can be
      used to remove and kill several types of bacteria found on the surface of the
      skin of processed broilers.

PMID- 18724770
TI  - Production of mycotoxins by Penicillium expansum inoculated into apples.
AB  - We investigated the production of mycotoxins in apple fruits inoculated with
      spores of 40 strains of apple blue mold, Penicillium expansum. Patulin and
      citrinin contents in the extracts from apples stored at 25 degrees C for 12 days
      after inoculation were determined by high-performance liquid chromatography
      (HPLC) analysis with UV and fluorescence detection. Patulin and citrinin were
      produced by 90% (36) and 80% (32) of the 40 strains, indicating that P. expansum
      is a consistent producer of these mycotoxins. The patulin content in the extracts
      was substantially higher than the citrinin content. Other mycotoxins whose
      production in pure culture has been reported were simultaneously detected with
      high-resolution liquid chromatography-mass spectrometry (LC-MS) analysis with the
      positive ion mode of electrospray ionization. Along with patulin and citrinin,
      expansolides A and B were identified based on the HPLC and LC-MS spectral data
      and detected in 88% (35) of the extracts. The results indicate that P. expansum
      is a consistent producer of expansolides A and B in rotten areas of apple fruits.
      The findings raise the possibility that products from decayed apples might
      contain expansolides A and B in addition to patulin and citrinin.

PMID- 18724771
TI  - A rapid fluorescence assay for danofloxacin in beef muscle: effect of muscle type
      on limit of quantitation.
AB  - A simple, rapid fluorescence screening assay was applied to the analysis of beef
      muscle for danofloxacin at the U.S. tolerance level of 200 ng/g. Muscle samples
      were homogenized in acetic acid-acetonitrile, the resultant mixture centrifuged,
      and fluorescence of the supernatants was then measured. The significant
      difference between the fluorescence of control muscle sample extracts and
      extracts of samples fortified at 200 ng/g allowed for successful discrimination
      between the samples. Setting a threshold level at the average 200 ng/g fortified
      sample extract fluorescence -3sigma allowed for identification of potentially
      violative samples. Successful analysis of a group of blind fortified samples over
      a range of concentrations was accomplished in this manner, without any false
      negative results. The limits of quantitation for danofloxacin, as well as
      enrofloxacin, using this assay were determined in three types of beef muscle
      (hanging tenderloin, neck, and eye round steak), as well as in serum. Significant
      differences in limits of quantitation were found among the three different muscle
      types examined, with hanging tenderloin muscle providing the lowest value. This
      work not only shows the potential for use of the fluorescence screening assay as
      an alternative to currently used microbial or antibody-based assays for the
      analysis of danofloxacin in beef muscle, but also suggests that assays using beef
      muscle may vary in performance depending on the specific muscle selected for
      analysis.

PMID- 18724772
TI  - Bioprotective potential of lactic acid bacteria in malting and brewing.
AB  - Lactic acid bacteria (LAB) are naturally associated with many foods or their raw
      ingredients and are popularly used in food fermentation to enhance the sensory,
      aromatic, and textural properties of food. These microorganisms are well
      recognized for their biopreservative properties, which are achieved through the
      production of antimicrobial compounds such as lactic acid, diacetyl,
      bacteriocins, and other metabolites. The antifungal activity of certain LAB is
      less well characterized, but organic acids, as yet uncharacterized proteinaceous
      compounds, and cyclic dipeptides can inhibit the growth of some fungi. A variety
      of microbes are carried on raw materials used in beer brewing, rendering the
      process susceptible to contamination and often resulting in spoilage or inferior
      quality of the finished product. The application of antimicrobial-producing LAB
      at various points in the malting and brewing process could help to negate this
      problem, providing an added hurdle for spoilage organisms to overcome and leading
      to the production of a higher quality beer. This review outlines the
      bioprotective potential of LAB and its application with specific reference to the
      brewing industry.

PMID- 18724773
TI  - Safety aspects and implications of regulation of probiotic bacteria in food and
      food supplements.
AB  - The application of living bacteria as probiotics in food or food supplements
      requires a careful safety assessment. This review summarizes key issues
      concerning the safety aspects of bacteria added to particular products marketed
      for improvement of general health or treatment of (post)infectious symptoms. The
      bacteria used in such products should be completely safe; however, it can be
      challenging to provide evidence for absence of all virulence properties. In some
      cases, virulence factors have been detected in probiotic bacterial strains, and
      the implications of these traits for safety assessments are discussed. Horizontal
      gene transfer can result in acquisition of virulence genes or antimicrobial
      resistance in probiotic bacteria. Antimicrobial resistance in these bacteria can
      possibly aid the spread of undesired resistance in intestinal bacterial
      populations. The relative risk of such gene transfers is considered. The
      generation of complete bacterial genome sequences can both resolve and create
      safety issues. Current practices of safety assessment procedures in the United
      States and the European Union are briefly reviewed and a future outlook is
      provided.

PMID- 18724775
TI  - Alterations in methylation and expression levels of imprinted genes H19 and Igf2
      in the fetuses of diabetic mice.
AB  - The study aimed to reveal alterations in expression and methylation levels of the
      growth-related imprinted genes H19 and Igf2 in fetuses of diabetic mice. Diabetes
      was induced in female mice by intraperitoneal injection of streptozotocin. DNA
      and total RNA were extracted from fetuses obtained from diabetic and control dams
      on embryonic day (E) 14. Real-time RT-PCR analysis revealed that the mRNA
      expression of Igf2 in fetuses from diabetic mice was 0.65-fold of the control
      counterparts. Bisulfite genomic sequencing demonstrated that the methylation
      level of the H19-Igf2 imprint control region was 19.1% higher in diabetic fetuses
      than in those of control dams. In addition, the body weight of pups born to
      diabetic dams was 26.5% lower than that of the control group. The results
      indicate that maternal diabetes can affect fetal development by means of altered
      expression of imprinted genes. The modified genomic DNA methylation status of
      imprinting genes may account for the change in gene expression.

PMID- 18724776
TI  - Embryonic stem cells derived from C57BL/6J and C57BL/6N mice.
AB  - Mouse embryonic stem (ES) cells with the C57BL/6 genetic background allow the
      generation of knockout mice without the need to backcross to C57BL/6. However,
      C57BL/6 ES cells whose pluripotency after homologous recombination has been
      confirmed are not yet available from public cell banks. To facilitate the use of
      ES cells derived from C57BL/6 sublines in both biologic and medical research, we
      demonstrated that the use of knockout serum replacement as a medium supplement
      and 8-cell blastomeres as recipient embryos allowed establishment of ES cells and
      production of germline chimeric mice, respectively. Under effective conditions, a
      large number of ES cell lines were established from C57BL/6J and C57BL/6N
      blastocysts. The majority of ES cells in many cell lines obtained from both
      strains showed a normal chromosome number. Germline chimeric mice were generated
      from C57BL/6J and C57BL/6N ES cells. Finally, the ES cell line B6J-S1UTR, derived
      from C57BL/6J, was used for successful production of gene knockout mice. C57BL/6J
      ES (B6J-S1UTR and B6J-23UTR) and C57BL/6N ES (B6N-22UTR) cells are available from
      the cell bank of the BioResource Center at RIKEN Tsukuba Institute
      (http://www.brc.riken.jp/lab/cell/english/).

PMID- 18724777
TI  - Embryo transfer rederivation of C.B-17/Icr-Prkdc(scid) mice experimentally
      infected with mouse parvovirus 1.
AB  - We determined whether embryos derived from C.B-17/Icr-Prkdc(scid) (SCID) mice
      infected with mouse parvovirus (MPV) 1b and mated to MPV-naive B6C3F1 mice would
      transmit virus to naive recipient female mice and rederived progeny. Viral DNA
      was detected by quantitative PCR (qPCR) in lymphoid tissues, gonad, sperm, and
      feces of all MPV1b-inoculated SCID mice. Viral DNA was detected in 1 of 16
      aliquots of embryos from infected male SCID mice and in 12 of 18 aliquots of
      embryos from infected female SCID mice. All recipient female mice implanted with
      embryos from infected SCID male mice and their progeny were negative by serology
      and qPCR. In contrast, 3 of 5 recipient female mice implanted with embryos from
      infected SCID female mice and 14 of 15 progeny mice from these recipients were
      seropositive by multiplex fluorescent immunoassay (MFI) for MPV capsid antigen
      (rVP2). All of these mice were negative by MFI for parvovirus nonstructural
      protein antigen (rNS1) and by qPCR, with the exception of 1 recipient female
      mouse that displayed weak rNS1 seroreactivity and low levels of MPV DNA in
      lymphoid tissues. Seroreactivity to rVP2 declined over time in all progeny mice
      from infected SCID female mice until all were seronegative by 20 wk of age,
      consistent with maternal antibody transfer. Given that the high levels of MPV
      contamination detected in our experimentally infected SCID mice are unlikely in
      naturally infected immunocompetent mice, these data indicate that embryo transfer
      rederivation is effective for the eradication of MPV from infected colonies.

PMID- 18724774
TI  - The guinea pig as a model of infectious diseases.
AB  - The words 'guinea pig' are synonymous with scientific experimentation, but much
      less is known about this species than many other laboratory animals. This animal
      model has been used for approximately 200 y and was the first to be used in the
      study of infectious diseases such as tuberculosis and diphtheria. Today the
      guinea pig is used as a model for a number of infectious bacterial diseases,
      including pulmonary, sexually transmitted, ocular and aural, gastrointestinal,
      and other infections that threaten the lives of humans. Most studies on the
      immune response to these diseases, with potential therapies and vaccines, have
      been conducted in animal models (for example, mouse) that may have less
      similarity to humans because of the large number of immunologic reagents
      available for these other species. This review presents some of the diseases for
      which the guinea pig is regarded as the premier model to study infections because
      of its similarity to humans with regard to symptoms and immune response.
      Furthermore, for diseases in which guinea pigs share parallel pathogenesis of
      disease with humans, they are potentially the best animal model for designing
      treatments and vaccines. Future studies of immune regulation of these diseases,
      novel therapies, and preventative measures require the development of new
      immunologic reagents designed specifically for the guinea pig.

PMID- 18724778
TI  - Minute virus of mice: antibody response, viral shedding, and persistence of viral
      DNA in multiple strains of mice.
AB  - Minute virus of mice (MVM) is a major concern for laboratory animal facilities
      because it remains with considerably high prevalence despite strict barrier
      systems. The aim of this study was to elucidate potential risks associated with
      MVM infection by investigating the role of the genetic background on antibody
      production and persistence as well as viral shedding. Mice of various strains and
      stocks were inoculated oronasally with the immunosuppressive strain MVMi; in
      addition, natural infection was modeled through contact exposure. As determined
      by serology, seroconversion and serum levels of IgG differed considerably among
      strains and stocks, especially in the contact-exposed group. For example,
      C57BL/6J mice responded well to exposure in contrast to FVB/N, NMRI, ICR, and
      C3H/HeN mice. Titration studies indicated that the viral dose necessary to induce
      seroconversion was strain-dependent. Experiments to dissect the role of the major
      histocompatibility complex haplotype in the response to MVMi gave inconclusive
      results. To detect viral persistence, spleens and feces were analyzed by PCR at
      16 wk after exposure, and the infectivity of PCR-positive spleens was
      investigated by IP and oronasal inoculation of naive mice. Although DNA was
      detected in the spleens of some mice, feces remained negative, and naive mice
      were not infected by inoculation. In addition, viral shedding declined rapidly
      after day 20 postinoculation. In summary, the data show that seroconversion and
      antibody response to MVMi infection depend on the genetic background of mice,
      with the infective dose being a critical factor. The role of viral DNA in
      chronically infected mice will require further elucidation.

PMID- 18724779
TI  - An acute osteomyelitis model in traumatized rat tibiae involving sand as a
      foreign body, thermal injury, and bimicrobial contamination.
AB  - The multfactorial nature of bone injuries in modern warfare and emergency trauma
      patients warrants enhancement of existing models. To develop a more appropriate
      model, rat tibiae (n = 195) were mechanically injured, divided into 2 groups
      (with or without thermal injury), and contaminated with a range of Staphylococcus
      aureus (Cowan 1) inocula. In some experiments, S. aureus inocula also contained
      Escherichia coli or foreign bodies (sand or soil). The primary outcome measure
      was the amount of S. aureus remaining in the tibia (tibial bacterial load) 24 h
      after contamination, reported as log10 cfu/g bone. S. aureus showed ID50 and ID95
      values of 72 and 977 cfu, respectively. Values were lower than seen previously by
      using S. aureus strain SMH. S. aureus tibial bacterial loads were higher in
      tibiae with mechanical and thermal injury (log10 4.15 +/- 0.27 cfu/g) versus
      mechanical injury alone (log10 3.1 +/- 0.47 cfu/g, P = 0.028). The addition of E.
      coli to the S. aureus inoculum had no effect on tibial bacterial loads (S. aureus
      only, log10 4.24 +/- 0.92 cfu/g; S. aureus + E. coli, log10 4.1 +/- 1.0 cfu/g, P
      = 0.74). Sand, added as a foreign body, increased tibial bacterial load. Combined
      mechanical and thermal trauma of the tibia is associated with increased S. aureus
      tibial bacterial loads, increasing the risk of acute osteomyelitis. Understanding
      the interplay of mechanical and thermal injuries, bimicrobial contamination, and
      foreign bodies may improve our understanding of traumatic bone injuries and the
      pathogenesis of osteomyelitis.

PMID- 18724780
TI  - P26-based serodiagnosis for Bartonella spp. infection in cats.
AB  - Bartonella henselae P26 has been identified as an immunodominant antigen
      expressed during feline infection. We used antisera from cats experimentally
      infected with B. henselae (n = 6), B. clarridgeiae (n = 4), or B. koehlerae (n =
      2) and from a sample of naturally infected cats (B. henselae, n = 34; B.
      clarridgeiae, n = 1) to evaluate recombinant P26 (rP26) as a serodiagnostic
      antigen. Immunoblots using antisera from cats infected with B. henselae and B.
      clarridgeiae reacted strongly with rP26, whereas B. koehlerae antisera did not. A
      capture ELISA was designed to evaluate the kinetics of rP26 IgG in sera from
      experimentally infected cats. For B. henselae and B. clarridgeiae antisera, the
      kinetic profiles of reactivity were similar for rP26 capture ELISA and Bartonella
      spp. indirect fluorescence assay. However, for B. koehlerae antisera, reactivity
      in rP26 capture ELISA was consistently low. The serodiagnostic potential of rP26
      capture ELISA was evaluated using sera from cats with known Bartonella sp.
      exposure histories. All 24 (100%) uninfected cats were seronegative, and 33 of 35
      (94.3%) cats bacteremic for Bartonella spp. were seropositive. We propose that
      rP26-based serology can serve as a useful adjunct tool for the diagnosis of
      feline infection with B. henselae and B. clarridgeiae, but it may not be useful
      for feline infection with B. koehlerae.

PMID- 18724782
TI  - Interstitial myocardial fibrosis in a captive chimpanzee (Pan troglodytes)
      population.
AB  - The clinical and necropsy records of 36 (25 male and 11 female) chimpanzees age
      10 to 40 y old that died over a 6-y period (2001 to 2006) were reviewed. All
      animals had annual physical exams that included electrocardiograms and serial
      blood pressures. Nine of the 36 animals had a complete cardiac evaluation by a
      board certified veterinary cardiologist, and 7 of the 36 animals (19%) were
      diagnosed with some form of cardiomyopathy. Systemic hypertension was noted in 3
      cases. Cardiac arrhythmias (ventricular ectopy) were seen in 15 (12 male and 3
      female) of the 36 animals (42%). Sudden cardiac death (SCD) occurred in 13 (11
      male and 2 female) chimps (36%) and was the leading cause of death (n = 13),
      followed by renal failure (n = 9) and septicemia (n = 3). Histologic examination
      of the hearts revealed interstitial myocardial fibrosis (IMF) in 29 chimpanzees
      (81%), and all of the animals that died suddenly due to cardiac causes had IMF to
      varying degrees. More data will be needed to identify the possible causes of IMF
      in captive chimpanzees, and IMF may be associated with arrhythmias and SCD in
      these animals.

PMID- 18724783
TI  - Lateral femoral hernias in a line of FVB/NHsd mice: a new confounding lesion
      linked to genetic background?
AB  - Several strains of transgenic mice derived from an inbred FVB/NHsd colony
      developed large masses on 1 or both flanks. Although originally suspected to be a
      phenotypic anomaly related to genetic modifications, nontransgenic littermates
      subsequently were affected with equal frequency, inculpating the FVB/NHsd founder
      colony. The masses were subcutaneous, soft, and exophytic and appeared over the
      course of a few weeks. Female mice were affected more frequently than males.
      Gross examination revealed the masses to consist of uni- or bilateral hernias of
      variable size, occasionally containing small or large intestine (or both), cecum,
      mesenteric adipose tissue, male reproductive organs, and ureters. All hernial
      sacs pouched through the femoral triangle laterally to the femoral vessels and
      therefore were classified as lateral femoral hernias. Lateral femoral hernias
      have not previously been described in the veterinary literature and have never
      been described as background lesions in a strain of mice. Our findings suggest
      likely genetic drift in this strain of FVB/NHsd mice, causing a background lesion
      that confounded phenotypic analyses of transgenic mice derived from this strain.

PMID- 18724781
TI  - Androgen resistance in squirrel monkeys (Saimiri spp.).
AB  - The goal of this study was to understand the basis for high androgen levels in
      squirrel monkeys (Saimiri spp.). Mass spectrometry was used to analyze serum
      testosterone, androstenedione, and dihydrotestosterone of male squirrel monkeys
      during the nonbreeding (n = 7) and breeding (n = 10) seasons. All hormone levels
      were elevated compared with those of humans, even during the nonbreeding season;
      the highest levels occurred during the breeding season. The ratio of testosterone
      to dihydrotestosterone in squirrel monkeys is high during the breeding season
      compared to man. Squirrel monkeys may have high testosterone to compensate for
      inefficient metabolism to dihydrotestosterone. We also investigated whether
      squirrel monkeys have high androgens to compensate for low-activity androgen
      receptors (AR). The response to dihydrotestosterone in squirrel monkey cells
      transfected with AR and AR-responsive reporter plasmids was 4-fold, compared with
      28-fold in human cells. This result was not due to overexpression of cellular
      FKBP51, which causes glucocorticoid and progestin resistance in squirrel monkeys,
      because overexpression of FKBP51 had no effect on dihydrotestosterone-stimulated
      reporter activity in a human fibroblast cell line. To test whether the inherently
      low levels of FKBP52 in squirrel monkeys contribute to androgen insensitivity,
      squirrel monkey cells were transfected with an AR expression plasmid, an AR
      responsive reporter plasmid, and a plasmid expressing FKBP52. Expression of
      FKBP52 decreased the EC50 or increased the maximal response to
      dihydrotestosterone. Therefore, the high androgen levels in squirrel monkeys
      likely compensate for their relatively low 5 alpha-reductase activity during the
      breeding season and AR insensitivity resulting from low cellular levels of
      FKBP52.

PMID- 18724784
TI  - Suicide and life-threatening behavior. In this issue.

PMID- 18724785
TI  - Antidepressant prescription and suicide rates: effect of age and gender.
AB  - To determine whether the effect of antidepressant exposure on suicide rate is
      modified by age and gender in Hungary, annual antidepressant prescription rates
      and suicide rates of about 10 million inhabitants between 1999-2005 were analyzed
      by age and gender groups. The suicide rate was inversely related to the increased
      use of antidepressants in both genders. The strongest association was found in
      the oldest age groups, where the increase in antidepressant use was highest,
      while there was no association in the under 20 or 50-69 age groups in either
      gender. Antidepressant prescription rate was related to suicide rate after
      controlling for divorce rate or unemployment rate, but not after controlling for
      alcohol consumption rate.

PMID- 18724786
TI  - What do suicide survivors tell us they need? Results of a pilot study.
AB  - Few studies have examined the natural coping efforts used by suicide survivors,
      or have identified specific problems and needs survivors experience following the
      death of a significant other by suicide. In the present study, we used a newly
      developed needs assessment survey to examine four areas of natural coping
      efforts: practical, psychological, and social difficulties; formal and informal
      sources of support; resources utilized in healing; and barriers to finding
      support since the loss. Sixty-three adult survivors of suicide were recruited
      from suicide survivor conferences and support groups. Results indicate that
      participants experienced high levels of psychological distress since the suicide,
      including elevated symptoms of depression, guilt, anxiety, and trauma.
      Participants experienced substantial difficulties in the social arena (e.g.,
      talking with others about the suicide). The majority of the sample viewed
      professional help as beneficial; although many informal sources of support were
      also valued (e.g., one-to-one contact with other survivors). Depression and a
      lack of information about where to find help served as barriers to help-seeking
      behaviors for our participants. Participants who reported higher levels of
      functional impairment were more likely to report higher levels of psychological
      distress, social isolation, and barriers to seeking help. Future research with a
      longitudinal and more inclusive sample is needed to build on these preliminary
      findings and to provide a solid foundation for evidenced-based interventions with
      survivors.

PMID- 18724787
TI  - Prevalence of suicidal ideation among boys and men assessed annually from ages 9
      to 29 years.
AB  - In a sample of 206 boys (90% Caucasian), self-reported suicidal ideation (SI;
      ages 12 to 29) and parent-reported youth suicidal talk (ages 9 to 20) were
      assessed annually by questionnaire. One-week point prevalence of self-reported SI
      ranged from 2.6% to 16.3%. New cases emerged across adolescence; by age 29, 57.3%
      self-reported SI at least once. SI was associated with clinically significant
      elevations on concurrent depressive symptoms. Nearly one quarter (24.8%) of
      parents reported suicidal talk by their son by age 20. Parent- and self-reports
      showed low correspondence. SI was more common than retrospective studies suggest.
      Parent-reports and one-time self-reports are likely to miss large numbers of
      adolescent boys who may be at risk.

PMID- 18724788
TI  - Correlates of suicidality among patients with psychotic depression.
AB  - The independent association of age and other factors with suicidality in patients
      with major depression with psychotic features was examined. Of the 183 study
      participants, 21% had a suicide attempt during the current episode. Male gender,
      Hispanic background, past suicide attempt, higher depression scores, and higher
      cognitive scores were each independently associated with greater intensity of
      current suicidality. Older age was independently associated with a lower risk of
      a lifetime suicide attempt. These findings reinforce the evidence that patients
      with psychotic depression are at high risk for suicide and underscore the
      importance of examining correlates of suicidality specific to patients with
      psychotic depression.

PMID- 18724789
TI  - Current suicide proneness and past suicidal behavior in adjudicated adolescents.
AB  - Youth recently assigned to probation (n = 233) were assessed for current suicide
      proneness, depression, and hopelessness, as well as for recent suicide ideation,
      previous suicide ideation, or suicide attempt(s). The Life Attitudes Schedule
      Short Form (LAS-SF) was used to assess suicide proneness. As per the LAS-SF,
      suicide proneness was defined broadly to include current engagement in overtly
      suicidal behavior as well as in risk-taking and potentially injury-producing
      behaviors, coupled with a lack of engagement in health and safety behaviors, or
      self-enhancement behaviors. As expected, current suicide proneness was
      significantly associated with a history of suicide ideation and attempts, recent
      ideation, and current depression and hopelessness for adjudicated youth. Gender
      differences were obtained between the strength of the association between suicide
      proneness and depressive symptoms. A subgroup of adjudicated youth (n = 39) was
      then interviewed about their suicidal behaviors. Among other things, these youth
      indicated that the majority of their previous suicide attempts were committed
      impulsively.

PMID- 18724790
TI  - Suicidal ideation in college students varies across semesters: the mediating role
      of belongingness.
AB  - The interpersonal-psychological theory of suicidal behavior (Joiner, 2005)
      proposes that the need to belong is fundamental; when met it can prevent suicide
      and when thwarted it can substantially increase the risk for suicide. We
      investigate one source of group-wide variation in belongingness among college
      students--changes in the social composition of college campuses across academic
      semesters--as an explanation for variation in suicidal ideation across the
      academic year. Our results indicate that in a sample of college students at a
      large southern state university (n = 309), suicidal ideation varied across
      academic semesters, with highest levels in summer compared to both spring and
      fall. Differences in suicidal ideation between summer and spring were, in large
      part, accounted for by belongingness. Theoretical, as well as practical,
      implications are discussed regarding mechanisms for seasonal variation in
      suicidal ideation.

PMID- 18724791
TI  - Social and racial correlates of Russian roulette.
AB  - The epidemiology of a neglected form of suicidal behavior, Russian roulette, is
      addressed. Also tested is an explanation of racial differences based on the
      opportunity theory of deviant behavior related to the availability of revolvers,
      necessary weapons with which to play Russian roulette. Data refer to 15 cases of
      Russian roulette found through a search of the medical examiner's suicide files
      (N = 1,412) and 75 matched controls who suicided by a gunshot to the head. The
      results support an opportunity perspective: 80% of the Russian roulette victims
      were African American compared to 30.7% of the controls. Further, among the
      controls, Blacks were three times more likely than Whites to use revolvers in
      suicides, a pattern indicating Blacks' greater access to revolvers. Russian
      roulette victims were entirely male, significantly younger, and less apt to be
      married than the control group.

PMID- 18724792
TI  - Identifying the risk of deliberate self-harm among young prisoners by means of
      coping typologies.
AB  - Self-harming behavior during incarceration has been a topic of increasing
      attention in recent years. Some authors attribute these episodes to the high
      level of stress that imprisonment generates coupled with a low quality of coping
      strategies employed by inmates. The main aim of this study was to identify, by
      means of coping typologies, prisoners at higher risk of self-harming behavior.
      The results highlighted the fact that coping typologies permitted the
      classification of inmates into four groups and the identification of those at
      lower and higher risk of self-harming. The group at greater risk was the one that
      used more avoidance and less approach coping.

PMID- 18724793
TI  - Inpatient suicide in a Chinese psychiatric hospital.
AB  - Little is known about the risk factors for suicide among psychiatric inpatients
      in China. In this study we identified the risk factors of suicide among
      psychiatric inpatients at Guangzhou Psychiatric Hospital. All psychiatric
      inpatients who died by suicide during the 1956-2005 period were included in this
      study. Using a case-control design, 64 inpatients with schizophrenia who died by
      suicide were compared with a matched 64 controls. The results indicate that the
      rate of suicide was 133.1/100,000 admissions (95%CI 103.4-162.9). There were no
      significant differences in the method, location, or time of suicide between male
      and female inpatients. The number of hospitalizations was significantly larger in
      the suicide group than that in the control group. In logistic regression
      analyses, guilty thought, depressive mood, and suicidal ideation and suicide
      attempt 1 month before hospital admission were identified as independent
      predictors of suicide among inpatients with schizophrenia. The findings of risk
      factors for schizophrenic inpatient suicide should be taken into account when
      developing interventions to prevent suicide among these patients.

PMID- 18724794
TI  - Attempted suicide among Iranian population.
AB  - Predictors of suicide attempts in Iran, to distinguish any similarities and
      differences of these predictors between suicide attempts in Iran and other
      developed and developing countries and to investigate the relation between
      general psychiatric symptoms and repetition of suicidal attempts were assessed.
      The validated Farsi version of the General Health Questionnaire-28 (GHQ-28) was
      used to assess multiple dimensions of quality of life of suicide attempters as
      depression, anxiety, social dysfunction, and somatic symptoms. Pivotal
      differences emerged in the clinical profiles of suicide attempters living in a
      developing country versus developed countries. In developing countries, those who
      attempt suicides are more likely to have no psychiatric disorder and are less
      likely to have used alcohol as part of the suicide attempt, but are more likely
      to have been assaulted physically or verbally. The results on the GHQ-28 indicate
      that the process through which individuals move from suicidal thought to action
      may decrease multiple dimensions of quality of life.

PMID- 18724795
TI  - Socio-cultural features and sex profile of the individuals with serious suicide
      attempts in southeastern Turkey: a one-year survey.
AB  - Our objective was to elucidate potential causes of higher rates of suicide
      attempts in females compared to males in southeastern Turkey through a 1-year
      survey. Gender-related differences observed in 96 subjects who attempted suicide
      by poisoning for the first time were as follows: in comparison to male, females
      were predominantly within the age interval of 15-24 years, experienced more
      stressful events in the previous week before suicide attempt, had lower education
      level, and had a lower rate of employment. One year after the suicide attempt,
      unfavorable attitude of family, lack of support, persisting unfavorable lifestyle
      comparable with that prior to the first attempt, and higher rates of domestic
      violence were more pronounced in females compared to males. These findings might
      be contributing factors to the higher suicide attempt rates observed in females
      compared to the males.

PMID- 18724796
TI  - A comment on Rory C. O'Connor's "The relations between perfectionism and
      suicidality: a systematic review".

PMID- 18724797
TI  - Of love and death: the emerging role of romantic disruption in suicidal behavior.

PMID- 18724799
TI  - Efficient genetic reprogramming of unmodified somatic neural progenitors uncovers
      the essential requirement of Oct4 and Klf4.
AB  - Significant breakthroughs have been recently achieved in reprogramming somatic
      cells to a pluripotent embryonic state by the ectopic expression of specific
      transcription factors. One of the major drawbacks of reprogramming strategies
      lays in the low efficiency of the process. It is likely that the required complex
      epigenetic-remodeling events could be cell-type specific and more rational
      approaches to cell source selection might help to improve the outcome of the
      procedure. Because the use of somatic stem cells, and specifically neural stem
      cells (NSCs), as nuclear donors significantly increased the efficiency of somatic
      cell nuclear transfer, we aimed to determine whether genetically unmodified
      somatic NSCs could be more easily reprogrammed to pluripotency than unmodified
      mouse embryonic fibroblasts. Retroviral transduction of the factors Oct4, Sox2,
      Klf4, and c-Myc successfully reverted NSCs to a pluripotent embryonic stem cell
      like state with a 2-fold efficiency increase, faster kinetic, and with a lower
      number of viral integrations. Quantification analysis of reprogramming-associated
      genes revealed that NSCs endogenously expressed high levels of Sox2 and c-Myc.
      Accordingly, NSCs could be successfully induced to pluripotency through the
      ectopic viral expression of the other two factors (Oct4 and Klf4). These findings
      suggest that endogenous expression of reprogramming genes could help the
      reprogramming process and somatic stem cells might be more prone to reprogramming
      due to their specific genetic background. Genetic-based somatic cell screening
      might provide essential information for the selection of alternative cell sources
      more suitable to direct reprogramming.

PMID- 18724801
TI  - Household survey in two provinces in Viet Nam estimates HIV prevalence in an
      urban and a rural population.
AB  - A household-based population study interviewed 2,553 women and 1,984 men aged 15
      49 years in urban (Ho Chi Minh City) and rural (Thai Binh) provinces in Viet Nam
      between July and August 2005. The survey response rate was high--approximately
      97% of households and 93% of adults overall, with a >92% acceptance of HIV
      testing among eligible adults. The unadjusted estimated population HIV prevalence
      was 0.3% (confidence interval [CI]: 0.1-0.6%) in Thai Binh and 0.7% (CI: 0.3-1.3)
      in Ho Chi Minh City (HCMC), compared with the national estimates and projections
      of 0.352% and 1.250%, respectively, for 2005. The ratio of male-to-female
      prevalence was 10.5:1 in Thai Binh and 1.3:1 in HCMC. A low level of men reported
      purchasing sex in the last 12 months (2.4%) and there were low self-reports of
      sexually transmitted infections in all adults (5%). A correct knowledge of
      HIV/AIDS prevention methods was high in both provinces (83%), although only 24.8%
      of women knew of the use of antiretroviral therapy to prevent vertical
      transmission of HIV. The observed population prevalence was consistent with
      recent projections in Thai Binh, although lower than expected in HCMC, indicating
      the substantial downward revisions of projected population HIV prevalence may
      need to be extended. The unequal sex prevalence ratio is consistent with the
      projected trends of increasing male-to-female sexual transmission in urban areas.
      The results and experience of this study will inform future population based
      surveys in Viet Nam and the broader Asian region.

PMID- 18724802
TI  - A report on the effect of commencing enfuvirtide on peripheral neuropathy.
AB  - Enfuvirtide is the first fusion inhibitor approved for use in HIV treatment and
      is a useful therapeutic option for highly treatment experienced individuals.
      Passive reporting has associated increased neuropathy rates with enfuvirtide use
      in some early studies but not others. The aim of this study was to describe any
      functional or clinical changes consistent with neuropathy among enfuvirtide
      users. A prospective cohort study of patients commencing or continuing
      enfuvirtide at a state HIV referral service, including clinical and sensory
      threshold monitoring, was conducted. A total of 14 patients were studied. All had
      advanced HIV disease and 13 (93%) had symptoms and/or signs consistent with
      neuropathy at baseline. Patients who entered the study on enfuvirtide-based
      therapy remained neurologically stable throughout follow-up. Eleven patients were
      assessed preand postenfuvirtide. No evidence was found for any clear effect of
      enfuvirtide on neuropathic symptoms, neuropathic signs, or sensory thresholds at
      a cohort level (p > 0.3 for all, Wilcoxon signed rank test). However, three (21%)
      patients experienced worsening of existing neuropathy symptoms (transient in two
      cases) and two (14%) patients' symptoms improved with enfuvirtide commencement.
      Breakthrough HIV viremia was associated with worsening symptoms in two patients
      at 5 and 18 months of enfuvirtide use. This study found no clear effect on
      peripheral nerves from enfuvirtide. Although limited by a small sample size, this
      study involved patients who would have been particularly vulnerable to a
      neurotoxin, with advanced HIV disease and a high rate of baseline neurological
      abnormalities. We observed no clear evidence of neurotoxicity from enfuvirtide in
      this population.

PMID- 18724803
TI  - Simple adherence assessments to predict virologic failure among HIV-infected
      adults with discordant immunologic and clinical responses to antiretroviral
      therapy.
AB  - We evaluated the association between two antiretroviral therapy (ART) adherence
      measurements--the medication possession ratio (MPR) and patient self-report--and
      detectable HIV viremia in the setting of rapid service scale-up in Lusaka,
      Zambia. Drug adherence and outcomes were assessed in a subset of patients
      suspected of treatment failure based on discordant clinical and immunologic
      responses to ART. A total of 913 patients were included in this analysis, with a
      median time of 744 days (Q1, Q3: 511, 919 days) from ART initiation to viral load
      (VL) measurement. On aggregate over the period of follow-up, 531 (58%) had
      optimal adherence (MPR > or =95%), 306 (34%) had suboptimal adherence (MPR 80
      94%), and 76 (8%) had poor adherence (MPR <80%). Of the 913 patients, 238 (26%)
      had VL > or =400 copies/ml when tested. When compared to individuals with optimal
      adherence, there was increasing risk for virologic failure in those with
      suboptimal adherence [adjusted relative risk (ARR): 1.3; 95% confidence interval
      (CI): 1.0, 1.6] and those with poor adherence (ARR: 1.7; 95% CI: 1.3, 2.4) based
      on MPR. During the antiretroviral treatment course, 676 patients (74%) reported
      no missed doses. The proportion of patients with virologic failure did not differ
      significantly among those reporting any missed dose from those reporting perfect
      adherence (26% vs. 26%, p = 0.97). Among patients with suspected treatment
      failure, a lower MPR was associated with higher rates of detectable viremia.
      However, the suboptimal sensitivity and specificity of MPR limit its utility as a
      sole predictor of virologic failure.

PMID- 18724804
TI  - NK-associated regulatory receptors in a structured HAART interruption of HIV-1
      positive individuals.
AB  - Since highly active antiretroviral therapy (HAART) was introduced a decade ago,
      it has been shown to be effective in keeping HIV-1 replication under control.
      Nevertheless, it is also known that HAART has certain limitations, such as its
      inability to completely inhibit the viral replication that maintains virus
      reservoirs, its high toxicity when the treatment is maintained for long periods
      of time, and the appearance of viral resistance to the therapy. These limitations
      have led to the introduction of structured treatment interruption (STI) of
      antiretroviral therapy, the principle of which is to reduce the clinical
      complications of HAART, and hypothetically to boost the cellular immune response
      of the patient host. The aim of this study was to analyze for the first time the
      impact of STI on the innate immune system. Specifically, we analyzed NK cells and
      their regulatory receptors (KIRs, NKG2, NCRs, and ILTs) and the cytokines that
      might control the NK response. Six months after the initiation of STI, the
      results revealed in most patients a significant increase in NK cells expressing
      ILT2 and NKp46 receptors. Slight or no changes were observed in other parameters
      studied, either during interruption or when HAART was reintroduced. Our data show
      that the STI strategy, irrespective of whether it improved the patients' clinical
      evolution, induced functional phenotype changes in NK cell subsets.

PMID- 18724806
TI  - Swiss MedLab 2008: International Congress, September 16-19, 2008, Montreux,
      Switzerland. Abstracts.

PMID- 18724807
TI  - 4th Biologie Prospective Santorini Conference, September 21-23, 2008, Santorini,
      Greece. Abstracts.

PMID- 18724805
TI  - CD4+ T-cell decline after the interruption of antiretroviral therapy in ACTG
      A5170 is predicted by differential expression of genes in the ras signaling
      pathway.
AB  - Patterns of expressed genes examined in cryopreserved peripheral blood
      mononuclear cells (PBMCs) of seropositive persons electing to stop antiretroviral
      therapy in the AIDS Clinical Trials Group Study A5170 were scrutinized to
      identify markers capable of predicting the likelihood of CD4+ T-cell depletion
      after cessation of antiretroviral therapy (ART). A5170 was a multicenter, 96
      week, prospective study of HIV-infected patients with immunological preservation
      on ART who elected to interrupt therapy. Study entry required that the CD4 count
      was greater than 350 cells/mm(3) within 6 months of ART initiation. Median nadir
      CD4 count of enrollees was 436 cells/mm(3). Two cohorts, matched for clinical
      characteristics, were selected from A5170. Twenty-four patients with an absolute
      CD4 cell decline of less that 20% at week 24 (good outcome group) and 24 with a
      CD4 cell decline of >20% (poor outcome group) were studied. The good outcome
      group had a decline in CD4+ Tcell count that was 50% less than the poor outcome
      group. Significance analysis of microarrays identified differential gene
      expression (DE) in the two groups in data obtained from Affymetrix Human FOCUS
      GeneChips. DE was significantly higher in the poor outcome group than in the good
      outcome group. Prediction analysis of microarrays (PAM-R) identified genes that
      classified persons as to progression with greater than 80% accuracy at therapy
      interruption (TI) as well as at 24 weeks after TI. Gene set enrichment analysis
      (GSEA) identified a set of genes in the Ras signaling pathway, associated with
      the downregulation of apoptosis, as significantly upregulated in the good outcome
      group at cessation of ART. These observations identify specific host cell
      processes associated with differential outcome in this cohort after TI.

PMID- 18724808
TI  - An improved quality control for bisulfite-PCR-based DNA methylation analysis:
      cycle threshold value.
AB  - BACKGROUND: The diagnostic potential of DNA methylation has generated a need for
      quality control systems in its analysis. Here, we tested whether cycle threshold
      (Ct) values from real-time quantitative PCR correlate better with the reliability
      of bisulfite-PCR methylation analyses than spectrophotometric concentrations.
      METHODS: A total of 18 cell line DNA samples were quantified for beta-actin
      (ACTB) Ct and spectrophotometric values from 1-microL volumes. A further 1 microL
      was analyzed in quintuplicate for bisulfite DNA ACTB by MethyLight. Correlations
      between Ct and spectrophotometric values, and MethyLight qualitative (detection
      in all replicates) and quantitative (Ct value standard deviation <1) reliability
      were compared. To validate the findings, the same comparisons were made in 40
      formalin-fixed, paraffin-embedded tissue (FFPET) samples analyzed by methylation
      specific PCR of MLH1. RESULTS: Using optimal thresholds, Ct values correctly
      identified 6/7 (86%) and 11/11 (100%) cell line samples to be qualitatively, and
      7/7 (100%) and 4/4 (100%) quantitatively reliable and unreliable, respectively.
      The corresponding frequencies for spectrophotometry were 6/8 (75%), 10/10 (100%),
      6/8 (75%) and 2/3 (67%), respectively. In FFPET DNA, the respective values for
      qualitative reliability for Ct values were 25/25 (100%) and 11/15 (73%), and
      11/14 (79%) and 8/26 (31%) for spectrophotometry. CONCLUSIONS: Ct values could be
      useful indicators for gauging the suitability of samples for methylation
      analysis, in particular from FFPET.

PMID- 18724809
TI  - Can E-cadherin and CD34 be used as indicators of prognosis for hepatocellular
      carcinoma patients?
AB  - BACKGROUND: The high postoperative recurrence of hepatocellular carcinoma (HCC)
      is a problem that would benefit from the identification of indicators of
      recurrence and prognosis. In the past few years, research has shown that E
      cadherin and CD34 can be used as indicators of the invasion of malignant tumors.
      In the present study, we investigated the expression of E-cadherin and CD34 in
      HCC patients. METHODS: Expression levels of E-cadherin and CD34 in 41 HCC samples
      were detected using two-step immunohistochemical methods and compared with
      clinical pathological parameters and survival rate. RESULTS: The positive rates
      of E-cadherin and CD34 expression in 41 HCC cases were 48.78% and 100%,
      respectively. Expression of E-cadherin was significantly lower in patients with
      larger tumors, a high risk invasion and Edmondson classification III or IV
      (p<0.05). There was a significant relationship between CD34 expression and age
      and tumor invasiveness (p<0.05). There was no significant relationship between
      expression of CD34 and E-cadherin by Spearman statistical analysis (p>0.05). The
      survival rate in patients with negative expression of E-cadherin was
      significantly lower. CONCLUSIONS: The expression of CD34 cannot be used singly as
      a prognostic indicator for HCC patients. The co-expression of E-cadherin and CD34
      cannot be used as a prognostic indicator for HCC patients. Clin Chem Lab Med
      2008;46:1122-6.

PMID- 18724810
TI  - Determination of serum creatinine by Jaffe method and how to calibrate to
      eliminate matrix interference problems.
AB  - BACKGROUND: The calibration of Jaffe method for serum creatinine using one serum
      based standard complemented with artificial matrix compensating standard's Jaffe
      interfering substances allows two-point calibration with results well comparable
      with enzymatic methods. METHOD: Spectrophotometry was used. RESULTS: Jaffe
      procedures compensating serum/plasma intereferents by subtracting a constant
      amount of creatinine poorly overcompensate creatinine in children. Two-point
      calibration with a pair of primary serum standards certified by the reference
      measurement procedure (isotope-dilution, mass spectrometry) or with a pair of
      secondary standards linked to primary materials could provide results well
      agreeable with enzymatic determination. Such a calibration comprises an
      absorbance offset corresponding to other-than-creatinine Jaffe-interfering
      chromogens present in standards in the calibration line, while a two-point
      calibration combining one standard with physiological saline/water always grossly
      distorts calibration line. We calculated/prepared artificial serum matrices
      capable of compensating Jaffe-interfering chromogens in serum standards. The
      combination of even one standard with its artificial matrix also enables two
      point calibration with practically the same results as with a pair of primary
      standards. CONCLUSIONS: A two-point calibration of Jaffe method for serum
      creatinine combining only one serum standard with creatinine solution matching
      standard's allow matrix-present interferents present results well comparable with
      enzymatic determination, providing the standard is attested/linked to the
      reference measurement procedure.

PMID- 18724811
TI  - Non-homogeneous separation of triglycerides, gamma-glutamyltransferase, C
      reactive protein and lactate dehydrogenase after centrifugation of lithium
      heparin tubes.
AB  - BACKGROUND: Clinical chemistry testing is influenced by a variety of
      preanalytical variables, including sample preparation. The presence of a diluted
      plasma layer at the top of primary tubes containing plasma citrate has recently
      been reported. However, no indication is available so far on the potential non
      homogeneous distribution of clinical chemistry analytes during centrifugation of
      primary tubes containing lithium-heparin as an additive. METHODS: A total of 40
      lithium-heparin plasma samples were collected from volunteers and immediately
      centrifuged. An aliquot was obtained from the upper 0.4 mL of plasma (upper
      aliquot), 1.0 mL of plasma was discarded, and a second aliquot (lower aliquot)
      was obtained from the remaining plasma. The concentrations of alanine
      aminotransferase, albumin, alkaline phosphatase, amylase, amylase pancreatic,
      aspartate aminotransferase, direct bilirubin, total bilirubin, blood urea
      nitrogen, calcium, chloride, cholesterol, C-reactive protein (CRP), creatinine,
      creatine kinase, gamma-glutamyltransferase (GGT), glucose, high-density
      lipoprotein-cholesterol, iron, lactate dehydrogenase (LDH), magnesium, phosphate,
      potassium, total protein, sodium, triglycerides and uric acid were assayed on a
      Roche/Hitachi Modular System P according to the manufacturer's specifications and
      using proprietary reagents. Sodium, chloride and potassium were measured on a
      Roche/Hitachi Modular System using indirect ion-selective electrode methods.
      RESULTS: We observed a statistically significant difference between the upper and
      lower aliquots for CRP (3.88+/-0.67 vs. 3.94+/-0.68 mg/L; p=0.025), GGT (32.1+/
      8.0 vs. 31.8+/-8.0 U/L; p=0.013), LDH (395+/-19 vs. 386+/-20 U/L; p=0.010) and
      triglycerides (1.29+/-0.09 vs. 1.27+/-0.09 mmol/L; p=0.001); results for the
      other analytes were not significantly different. In no case did the mean
      percentage bias recorded between aliquots exceed the current analytical quality
      specifications for desirable bias. CONCLUSIONS: The results of our investigation
      show that plasma layer stratification might occur in primary lithium-heparin
      tubes for a limited number of routine clinical chemistry tests, introducing a
      statistically significant bias in the measurement of GGT, LDH, triglycerides and
      CRP in the upper vs. the bottom section. When delayed testing is necessary for
      these parameters, we suggest that plasma should be separated after centrifugation
      and appropriately mixed before delayed/repeated analysis or aliquoting.

PMID- 18724812
TI  - Computer-assisted detection of monoclonal components: results from the
      multicenter study for the evaluation of CASPER (Computer Assisted Serum Protein
      Electrophoresis Recognizer) algorithm.
AB  - BACKGROUND: To investigate the potential use of Artificial Neural Network (ANN)
      in the evaluation of serum protein electrophoresis, we set up a multicenter study
      involving six Italian laboratories. For this purpose, we developed an algorithm
      named CASPER (Computer Assisted Serum Protein Electrophoresis Recognizer).
      METHODS: A total of 59,516 samples from the six centers were divided into three
      groups. Training and validation sets were used to develop the neural network,
      whereas evaluation set was used to test the performance of CASPER in recognizing
      abnormal electrophoretic profiles. RESULTS: CASPER showed 93.0% sensitivity and
      47.4% specificity. CASPER sensitivity and specificity ranged in the six sites
      from 88% (site 3) to 97% (site 5) and from 36% (site 6) to 53% (site 3),
      respectively. Sensitivity for gamma zone was 94.6%, for beta zone 89.7% and for
      oligoclonal patterns 92.0%. CONCLUSIONS: The sensitivity of the CASPER algorithm
      does not allow us to recommend its use as a replacement for the visual
      inspection, but it could be helpful in avoiding accidental misclassifications by
      the operator. Moreover, the CASPER algorithm may be a useful tool for training
      operators and students. This study evidenced a high inter-observer variability,
      which should be addressed in a dedicated study. Data set to train and validate
      ANNs should contain a huge range and an adequate number of different
      abnormalities.

PMID- 18724813
TI  - Optimization of imprecision and cost saving on hemoglobin A 1c controls through
      aliquot freezing.

PMID- 18724814
TI  - Estimation of glomerular filtration rate by the modification of diet in renal
      disease (MDRD) equation in patients with sickle cell disease.

PMID- 18724815
TI  - Development of monoclonal antibodies specific for the human sodium-dependent
      phosphate co-transporter NaPi2b.
AB  - Homeostasis of inorganic phosphate in the human body is maintained by regulated
      absorption, metabolism, and excretion. Sodium-dependent phosphate transporters
      (NaPi) mediate the transport of inorganic phosphate (P(i)) in cells in response
      to dietary phosphate consumption, hormones, and growth factors. NaPi2b is a
      member of the sodium-dependent phosphate transporter family, with a distinct
      pattern of expression and regulation. Signaling pathways activated by mitogens,
      glucocorticoids, and metabolic factors have been implicated in regulating P(i)
      transport via NaPi2b. Inactivation of NaPi2b function by mutations has been
      linked to human pathologies, such as pulmonary alveolar microlithiasis. In this
      study, we describe the generation and characterization of monoclonal antibodies
      against human NaPi2b. The monoclonal antibodies were shown to recognize
      specifically transiently overexpressed and endogenous NaPi2b in commonly used
      immunoassays, including Western blotting, immunoprecipitation, and
      immunohistochemistry. These properties make them particularly valuable reagents
      for elucidating NaPi2b function in health and disease.

PMID- 18724824
TI  - Effect of Borrelia burgdorferi genotype on the sensitivity of C6 and 2-tier
      testing in North American patients with culture-confirmed Lyme disease.
AB  - BACKGROUND: A potential concern with any serologic test to detect antibodies to
      Borrelia burgdorferi is whether the epitopes incorporated in the test provide
      sufficient cross-reactivity to detect infection with all of the pathogenic
      strains of the species. This is a particular concern for the C6 test, which is
      based on reactivity to a single peptide. METHODS: C6 testing and 2-tier testing
      were performed on acute-phase serum samples obtained from >158 patients with
      erythema migrans for whom the genotype of the borrelial isolate was defined on
      the basis of an analysis of the 16S-23S ribosomal DNA spacer region and/or on the
      genetic variation of the outer surface protein C gene (ospC). The sonicated whole
      cell-based enzyme-linked immunosorbent assay, the immunoblots used in the 2-tier
      testing, and the C6 assay all used antigens from B. burgdorferi sensu stricto
      strain B31. RESULTS: The sensitivity of C6 testing (69.5%) was greater than that
      of 2-tier testing (38.9%) (P<.001); the difference in sensitivity, however, was
      statistically significant only for patients infected with 2 of the 3 ribosomal
      spacer type-defined genotypes. The lower sensitivity of 2-tier testing was
      attributable to the low sensitivity of the immunoblot tests, rather than the
      first-tier enzyme-linked immunosorbent assay. There was also a trend for the
      sensitivity of 2-tier testing to vary according to the ospC genotype for the 14
      genotypes represented in the study (P=.07); this relationship was not observed
      with C6 testing. CONCLUSIONS: Lack of sensitivity of the C6 test because of
      strain diversity seems less likely to be a limitation of this serologic test,
      compared with 2-tier testing in North American patients with early Lyme disease.

PMID- 18724825
TI  - Relationship of pneumocystis antibody response to severity of chronic obstructive
      pulmonary disease.
AB  - Pneumocystis colonization has been associated with severity of chronic
      obstructive pulmonary disease (COPD). The relationship of Pneumocystis antibody
      status to COPD severity has not been investigated, but antibody levels might
      relate to both colonization susceptibility and COPD progression. We investigated
      anti-Pneumocystis antibody titers and airway obstruction in a cohort of patients
      with COPD. Undetectable anti-Pneumocystis antibody titer was an independent
      predictor of more-severe airway obstruction, although use of inhaled
      corticosteroids is a possible confounder of this effect.

PMID- 18724826
TI  - Three-year prospective study to improve the management of blood-exposure
      incidents.
AB  - OBJECTIVE: Throughout 2003-2005, all blood-exposure incidents registered by an
      expert counseling center in The Netherlands accessible by telephone 24 hours a
      day, 7 days a week, were analyzed to assess quality improvement in the center's
      management of such incidents. The expert center was established to handle blood
      exposure incidents that occur both inside and outside of a hospital. Infection
      control practitioners carried out risk assessment, made the practical
      arrangements associated with managing incidents, and carried out treatment and
      follow-up, all in accordance with standardized procedures. DESIGN: We analyzed
      the time it took for exposed individuals to report the incident, the time
      required to perform a human immunodeficiency virus (HIV) test for the source
      individual when needed, occurrence of injuries, hepatitis B (HBV) vaccination
      status of exposed individuals, and adherence to protocol at the expert center.
      RESULTS: A mean of 465 incidents was registered during each year of the 3-year
      study period. Although 698 (50%) of 1,394 reported exposures took place in a
      hospital, 704 (50%) took place outside of a hospital, and 460 (33%) occurred at a
      time other than regular office hours. HIV tests for source individuals were
      performed increasingly quickly over the course of the 3-year study period because
      of earlier reporting and improvements in practical matters associated with
      performing and processing the tests. The percentage of healthcare workers
      employed outside a hospital who were vaccinated against HBV increased from 34%
      (52 of 152) to 70% (119 of 170) during the 3-year study period. Consequently, the
      administration of immunoglobulin and unnecessary laboratory testing were reduced.
      In assessing the quality of the expert center, flaws in the handling of incidents
      were identified in 148 (37%) of 396 incidents analyzed in 2003, compared with 38
      (8%) of 461 incidents analyzed in 2005. CONCLUSIONS: The practical matters
      associated with management of blood-exposure incidents, such as timely reporting
      and administration of prophylaxis, should be optimized for incidents that occur
      at times other than regular office hours and outside of hospitals. The
      establishment of a 24-hour centralized counseling facility that was open 7 days a
      week to manage blood exposures resulted in significant improvements in incident
      management and better care.

PMID- 18724827
TI  - Effects of myofascial induction techniques on physiologic and psychologic
      parameters: a randomized controlled trial.
AB  - OBJECTIVES: The objective was to determine the effect of myofascial techniques on
      the modulation of physiologic and psychologic variables. DESIGN: Forty-one (41)
      healthy male volunteers were randomly assigned to an experimental or control
      group. INTERVENTIONS: The experimental group underwent 3 manual therapy
      modalities: suboccipital muscle technique, compression of fourth intracranial
      ventricle, and deep cervical fascia technique. The control group remained in a
      resting position for the same time period under the same environmental
      conditions. OUTCOME MEASURES: Temperature, heart rate, and systolic and diastolic
      blood pressure (BP) were measured before, during, and after the intervention.
      State and trait anxiety levels and depression level were evaluated before and
      after the intervention. RESULTS: Repeated-measures analysis of variance revealed
      a significant time x groups interaction [F = 4.7(1,40); p = 0.036] for state
      anxiety. There were no significant time x group interaction effects for
      depression [F = 0.33(1,40); p = 0.57] or trait anxiety [F = 3.76(1,40), p =
      0.060]. Among physiologic parameters, a significant time x group interaction was
      found for systolic BP [F = 2.86(6,240); p = 0.033] and heart rate [F =
      2.89(6,240); p = 0.036]. CONCLUSIONS: Psychologic modulation is observed after
      application of manual therapy techniques, with a decrease in state anxiety in the
      experimental group. Heart rate and systolic BP were modulated during the course
      of myofascial induction techniques. All of these effects were observed up to 20
      minutes after the therapy.

PMID- 18724828
TI  - Marked hyperthyroxinemia during amiodarone treatment revealing thyroid hormone
      resistance syndrome.

PMID- 18724829
TI  - Cytocompatibility of a novel, longitudinally microstructured collagen scaffold
      intended for nerve tissue repair.
AB  - Traumatic injury to the nervous system induces functional deficits as a result of
      axonal destruction and the formation of scar tissue, cystic cavitation, and
      physical gaps. Bioengineering bridging materials should ideally act as cell
      carriers for the implantation of axon growth-promoting glia, as well as
      supporting integration with host cell types. Here, we describe the
      cytocompatibility of a novel, micro-structured porcine collagen scaffold
      containing densely packed and highly orientated channels that, in three
      dimensional (3D) tissue culture, supports attachment, proliferation, aligned
      process extension, and directed migration by populations of glial cells
      (olfactory nerve ensheathing cells and astrocytes) and orientated axonal growth
      by neurons (differentiated human SH-SY5Y neuroblastoma cell line). The seeded
      glia required several weeks to penetrate deeply into the highly porous scaffold,
      where they adopted an orientated morphology similar to that displayed in simple
      2D cultures. The direct interaction between SH-SY5Y-derived nerve fibers and the
      collagen scaffold also resulted in highly orientated axonal growth. It is likely
      that biocompatible scaffolds that are capable of promoting glial cell attachment,
      migration, and highly orientated process outgrowth will be important for future
      repair strategies for traumatically injured nervous tissues.

PMID- 18724830
TI  - Ex vivo cultivation of corneal limbal epithelial cells in a thermoreversible
      polymer (Mebiol Gel) and their transplantation in rabbits: an animal model.
AB  - We evaluated the efficacy of autologous expanded corneal epithelial cell
      transplants derived from harvested limbal biopsy cultured on a thermoreversible
      polymer (Mebiol Gel) for the management of unilateral limbal stem cell deficiency
      (LSCD). Corneal limbal biopsies from 12 rabbits were cultured on a
      thermoreversible polymer Mebiol Gel at 37 degrees C. Cells were harvested from
      the dishes after 3 weeks by reducing temperature to 4 degrees C. Autologous
      transplantation was undertaken to reconstruct the experimentally induced limbal
      stem cell deficiency in the rabbit eyes. The corneas of both eyes of all rabbits
      were harvested later for molecular studies. Reparative surgery was a total
      success in seven rabbits, partial success in two, and failure in three eyes.
      Histology of the seven successful eyes showed the successful growth of the
      corneal epithelium. Immunohistochemistry and reverse transcriptase polymerase
      chain reaction showed the cornea phenotype and stem cell-associated markers in
      the limbus of the seven successful eyes, indicating the homing of these cells
      into limbus. In the three failure cases and in the two control rabbit eyes, used
      in the study, histology showed presence of goblet cells and vascularization in
      the stroma with abortive formation of corneal epithelium. Our results suggest
      that transplantation of autologous limbal epithelial cells grown in
      thermoreversible polymer Mebiol Gel may restore a nearly normal ocular epithelial
      surface in eyes with unilateral LSCD.

PMID- 18724831
TI  - Cell-matrix interactions improve beta-cell survival and insulin secretion in
      three-dimensional culture.
AB  - Controlled matrix interactions were presented to pancreatic beta-cells in three
      dimensional culture within poly(ethylene glycol) hydrogels. Dispersed MIN6 beta
      cells were encapsulated in gel environments containing the following entrapped
      extracellular matrix (ECM) proteins: collagen type I, collagen type IV,
      fibrinogen, fibronectin, laminin, and vitronectin. In ECM-containing gels, beta
      cell survival was significantly better than in gels without ECM over 10 days.
      Correspondingly, apoptosis in encapsulated beta-cells was less in the presence of
      each matrix protein, suggesting the ability of individual matrix interactions to
      prevent matrix signaling-related apoptosis (anoikis). MIN6 beta-cells cultured in
      gels containing collagen type IV or laminin secreted more insulin in response to
      glucose stimulation than beta-cells in all other experimental conditions.
      Variations in collagen type IV or laminin concentration between 10 microg/mL and
      250 microg/mL did not affect insulin secretion. Finally, beta-cell function in
      hydrogels presenting both collagen type IV and laminin revealed synergistic
      interactions. With a total protein concentration of 100 microg/mL, three gel
      compositions of varying ratios of collagen type IV to laminin (25:75, 50:50, and
      75:25) were tested. In the presence of 25 microg/mL of collagen type IV and 75
      microg/mL of laminin, beta-cell insulin secretion was greater than with laminin
      or collagen type IV individually. These results demonstrate that specific,
      rationally designed extracellular environments promote isolated beta-cell
      survival and function.

PMID- 18724832
TI  - Monolayer and spheroid culture of human liver hepatocellular carcinoma cell line
      cells demonstrate distinct global gene expression patterns and functional
      phenotypes.
AB  - Understanding cell biology of three-dimensional (3D) biological structures is
      important for more complete appreciation of in vivo tissue function and advancing
      ex vivo organ engineering efforts. To elucidate how 3D structure may affect
      hepatocyte cellular responses, we compared global gene expression of human liver
      hepatocellular carcinoma cell line (HepG2) cells cultured as monolayers on tissue
      culture dishes (TCDs) or as spheroids within rotating wall vessel (RWV)
      bioreactors. HepG2 cells grown in RWVs form spheroids up to 100 mum in diameter
      within 72 h and up to 1 mm with long-term culture. The actin cytoskeleton in
      monolayer cells show stress fiber formation while spheroids have cortical actin
      organization. Global gene expression analysis demonstrates upregulation of
      structural genes such as extracellular matrix, cytoskeletal, and adhesion
      molecules in monolayers, whereas RWV spheroids show upregulation of metabolic and
      synthetic genes, suggesting functional differences. Indeed, liver-specific
      functions of cytochrome P450 activity and albumin production are higher in the
      spheroids. Enhanced liver functions require maintenance of 3D structure and
      environment, because transfer of spheroids to a TCD results in spheroid
      disintegration and subsequent loss of function. These findings illustrate the
      importance of physical environment on cellular organization and its effects on
      hepatocyte processes.

PMID- 18724836
TI  - Sixth European Workshop on Periodontology of the European Academy of
      Periodontology at the Charterhouse at Ittingen, Thurgau, Switzerland.

PMID- 18724833
TI  - Neuroprotective and antiinflammatory properties of a novel demethylated
      curcuminoid.
AB  - A demethylated derivative of curcumin (DC; 67.8% bisdemethylcurcumin, 20.7%
      demethylmonodemethoxycurcumin, 5.86% bisdemethoxycurcumin, 2.58%
      demethylcurcumin) was prepared by using a 95% extract of curcumin (C(95); 72.2%
      curcumin, 18.8% monodemethoxycurcumin, 4.5% bisdemethoxycurcumin). DC increased
      glutathione and reduced reactive oxygen species (ROS) in HT4 neuronal cells. In a
      model of glutamate-induced death of HT4, DC was more effective than C(95) in
      neuroprotection. The protective effects of DC were retained even when DC was
      withdrawn from culture media after pretreatment. DC treatment, unlike an equal
      dose of C(95), completely spared glutamate-induced loss of cellular GSH. Both DC
      and C(95) prevented glutamate-induced elevation of cellular ROS but failed to
      attenuate glutamate-induced elevation of intracellular calcium. In human
      microvascular endothelial cells (HMECs) challenged with TNF-alpha, GeneChip
      analysis revealed that only a subcluster of 23 TNF-alpha-inducible genes were
      uniquely sensitive to C(95). In sharp contrast, 1,065 TNF-alpha-inducible genes
      were sensitive to DC but not to C(95), suggesting that DC was more effective in
      antagonizing the effects of TNF-alpha on HMECs. Functional analysis identified
      that the genes uniquely sensitive to DC belonged in four functional categories:
      cytokine-receptor interaction, focal adhesion, cell adhesion, and apoptosis. Real
      time PCR as well as ELISA studies demonstrated that TNF-alpha-inducible CXCL10
      and CXCL11 expression was sensitive to DC but not to C(95). Flow-cytometry
      studies recognized ICAM-1 and VCAM-1 as TNF-alpha-inducible adhesion molecules
      that were uniquely sensitive to DC. Taken together, DC exhibited promising
      neuroprotective and antiinflammatory properties that must be characterized in
      vivo.

PMID- 18724837
TI  - Innovations in non-surgical periodontal therapy: Consensus Report of the Sixth
      European Workshop on Periodontology.
AB  - INTRODUCTION: The remit of this working group was to update the existing
      knowledge base in non-surgical periodontal therapy. The published systematic
      reviews from the fourth EAP Workshop formed the starting point for this update
      and in addition specific innovations not covered in previous workshops were
      included. MATERIAL AND METHODS: The literature was systematically searched and
      critically reviewed. Five manuscripts were produced in five specific topics
      identified as areas where innovative approaches have been developed in non
      surgical periodontal therapy and which were deemed to be strategically important
      for patient care and clinical practice. RESULTS: The results and conclusions of
      the review process are presented in the following papers, together with the group
      consensus statements, clinical implications and directions for future research: A
      systematic review of the effects of full mouth debridement with and without
      antiseptics in patients with chronic periodontitis. Advances in Power Driven
      Instrumentation. Laser application in non-surgical periodontal therapy - a
      systematic review. Antimicrobial therapy in periodontitis: the use of systemic
      antimicrobials against the subgingival biofilm. The cost-effectiveness of
      supportive periodontal-care for patients with chronic periodontitis.

PMID- 18724838
TI  - A systematic review of the effects of full-mouth debridement with and without
      antiseptics in patients with chronic periodontitis.
AB  - OBJECTIVES: To assess the clinical and microbiological effects of full-mouth
      debridement with (FMD) and without the use of antiseptics [full-mouth scaling and
      root planing (FMSRP)] in comparison with conventional staged debridement (CSD) in
      patients with chronic periodontitis after at least 6 months. MATERIAL AND
      METHODS: The search in MEDLINE (PubMed), covering a period of 1975 to October
      2007, and hand searching yielded 207 titles. Forty-two abstracts and 17 full-text
      articles were screened for inclusion. RESULTS: Twelve articles allowed a direct
      comparison of FMD with CSD, FMSRP with CSD and FMD with FMSRP. Probing pocket
      depth reductions were significantly greater (0.2 mm) with FMD and FMSRP compared
      with CSD. Moreover, a modest reduction in BOP (9%) favoured FMD. Likewise,
      clinical attachment levels were improved by 0.2-0.4 mm in favour of FMD and
      FMSRP, respectively. In all comparisons, single-rooted teeth and deep pockets
      benefitted slightly from FMD and FMSRP. Limited differences in the changes of the
      subgingival microbiota were noted between the treatment modalities. CONCLUSIONS:
      Despite the significant differences of modest magnitude, FMD or FMSRP do not
      provide clinically relevant advantages over CSD. Hence, all three treatment
      modalities may be recommended for debridement in the initial treatment of
      patients with chronic periodontitis.

PMID- 18724839
TI  - Advances in power driven pocket/root instrumentation.
AB  - OBJECTIVES: The primary aim was: "Does power-driven pocket/root instrumentation
      offer a clinical advantage over hand instrumentation"? Secondary aim was to
      update knowledge base of power-driven instrumentation post Tunkel et al. (2002).
      MATERIAL AND METHODS: A literature search of power-driven instruments (in vitro,
      in vivo and controlled clinical trials) was performed from April 2001 using
      similar criteria to Tunkel et al. (2002). Primary outcome was whether power
      driven instruments offered an advantage over hand instrumentation; secondary
      outcomes were effect on root surface, effectiveness of new instrument designs,
      and role of biophysical effects such as cavitation. RESULTS: From a total of 41
      studies, 14 studies involved comparison of power-driven devices with hand
      instrumentation for non-surgical therapy. These were subdivided into new designs
      of power instrumentation, full-mouth debridement and irrigation and patient
      acceptance. Use of power-driven instrumentation provides similar clinical
      outcomes compared with hand instrumentation. Difficulty of pooling studies
      continues to hinder the drawing of definitive conclusions. CONCLUSION: Newer
      designs of powered instruments have not shown any benefit when compared with
      other ultrasonic devices in non-surgical periodontal therapy. New in vitro
      research shows there is variation in the performance of different tip designs and
      generators, but its clinical relevance remains unknown.

PMID- 18724840
TI  - Laser application in non-surgical periodontal therapy: a systematic review.
AB  - OBJECTIVES: The primary aim was to address the following focused question: What
      is the clinical effect of laser application compared with mechanical debridement
      in non-surgical periodontal therapy in patients with chronic periodontitis? A
      secondary aim was to survey the relevant literature in relation to safety of
      laser applications. MATERIAL AND METHODS: Electronic databases of the PubMed and
      the Cochrane Library were searched and completed by manual searches up to
      December 2007. RESULTS: Following screening, 12 publications (11 studies) were
      eligible for the review. A meta-analysis could not be performed due to the
      heterogeneity of the studies. The results from a narrative synthesis indicate
      that Er:YAG laser monotherapy resulted in similar clinical outcomes, both in the
      short and the long term (up to 24 months), compared with mechanical debridement.
      There is insufficient evidence to support the clinical application of either
      CO(2), Nd:YAG, Nd:YAP, or different diode laser wavelengths. CONCLUSIONS: The
      Er:YAG laser seems to possess characteristics most suitable for the non-surgical
      treatment of chronic periodontitis. Research conducted so far has indicated that
      its safety and effects might be expected to be within the range reported for
      conventional mechanical debridement. However, the evidence from the evaluated
      studies is weak.

PMID- 18724841
TI  - Antimicrobial therapy in periodontitis: the use of systemic antimicrobials
      against the subgingival biofilm.
AB  - OBJECTIVES: The aim was to answer three relevant questions: can systemic
      antimicrobials be efficacious if the biofilm is not disrupted? Can the type of
      debridement of the subgingival biofilm impact upon the clinical outcomes of the
      adjunctive antimicrobial therapy? Is the efficacy of the adjunctive systemic
      antimicrobial therapy dependent on the quality of the debridement of the
      subgingival biofilm and the sequence debridement-antibiotic usage? MATERIAL AND
      METHODS: Relevant papers were searched, critically analysed and their data were
      extracted. RESULTS: For the first question, studies assessing susceptibility of
      bacteria in biofilms, and clinical studies evaluating systemic antimicrobials as
      monotherapy, were reviewed. For the second question, clinical studies comparing
      systemic antimicrobials as adjuncts to non-surgical debridement or to periodontal
      surgery and clinical trials using systemic antibiotics with periodontal surgery
      were evaluated. For the third question, a previous systematic review was updated.
      CONCLUSION: If systemic antimicrobials are indicated in periodontal therapy, they
      should be adjunctive to mechanical debridement. There is not enough evidence to
      support their use with periodontal surgery. Indirect evidence suggests that
      antibiotic intake should start on the day of debridement completion, debridement
      should be completed within a short time (preferably <1 week) and with an adequate
      quality, to optimize the results.

PMID- 18724842
TI  - The cost-effectiveness of supportive periodontal care for patients with chronic
      periodontitis.
AB  - OBJECTIVE: To systematically evaluate the evidence for effectiveness of
      supportive periodontal care (SPC) provided in specialist care and general
      practice for patients with chronic periodontitis; to construct a model for the
      cost effectiveness of SPC. SEARCH STRATEGY: Electronic database searches of
      MEDLINE, EMBASE and SCOPUS were performed with hand searching of relevant
      journals and Workshops of Periodontology. SELECTION CRITERIA: SPC for patients
      with chronic periodontitis, at least 12 months follow-up and clinical attachment
      level as a primary outcome. RESULTS: Three articles addressed the question (Nyman
      et al. 1975, Axelsson & Lindhe 1981, Cortellini et al. 1994): Deltas CAL for
      patients undergoing "specialist" SPC were 0.1 mm (2 years), 0.2 mm (6 years) and 
      0.01 mm (3 years) respectively. In generalist care the Deltas CAL during SPC were
      -2.2, -1.8 and -2.8 mm. Differences between specialist and generalist SPC were an
      extra 20.59 tooth years and 3.95 mm attachment loss for generalist SPC.
      Incremental cost-effectiveness ratios were an extra 288 euros for one tooth year
      or an extra 1503 euros/1 mm reduction in loss of attachment for SPC delivered in
      specialist care. CONCLUSION: SPC delivered in specialist as compared with general
      practice will result in greater stability of clinical attachment but this will be
      achieved at relatively greater cost.

PMID- 18724843
TI  - Periodontal tissue engineering and regeneration: Consensus Report of the Sixth
      European Workshop on Periodontology.
AB  - AIM: To review the scientific preclinical background and clinical studies of
      current methods of periodontal regeneration in the treatment of infrabony defects
      and soft tissue deficiencies. METHOD: Five commissioned review papers including
      two systematic reviews were scrutinized by a group of experts in order to derive
      consensus conclusions, clinical relevance/implications and to propose future
      research requirements. RESULTS: The following five papers were assessed: 1.
      Biological mediators and periodontal regeneration: a review of enamel matrix
      proteins at the cellular and molecular levels. 2. Regeneration of periodontal
      tissues: combination of barrier membranes and grafting materials - Biological
      foundation and preclinical evidence. 3. Clinical outcomes with bioactive agents
      alone or in combination with grafting or GTR 4. Treatment of gingival recession
      with coronally advanced flap procedures. A systematic review. 5. Soft tissue
      management at implant sites.

PMID- 18724844
TI  - Biological mediators and periodontal regeneration: a review of enamel matrix
      proteins at the cellular and molecular levels.
AB  - BACKGROUND: Despite a large body of clinical and histological data demonstrating
      beneficial effects of enamel matrix proteins (EMPs) for regenerative periodontal
      therapy, it is less clear how the available biological data can explain the
      mechanisms underlying the supportive effects of EMPs. OBJECTIVE: To analyse all
      available biological data of EMPs at the cellular and molecular levels that are
      relevant in the context of periodontal wound healing and tissue formation.
      METHODS: A stringent systematic approach was applied using the key words "enamel
      matrix proteins" OR "enamel matrix derivative" OR "emdogain" OR "amelogenin". The
      literature search was performed separately for epithelial cells, gingival
      fibroblasts, periodontal ligament cells, cementoblasts,
      osteogenic/chondrogenic/bone marrow cells, wound healing, and bacteria. RESULTS:
      A total of 103 papers met the inclusion criteria. EMPs affect many different cell
      types. Overall, the available data show that EMPs have effects on: (1) cell
      attachment, spreading, and chemotaxis; (2) cell proliferation and survival; (3)
      expression of transcription factors; (4) expression of growth factors, cytokines,
      extracellular matrix constituents, and other macromolecules; and (5) expression
      of molecules involved in the regulation of bone remodelling. CONCLUSION: All
      together, the data analysis provides strong evidence for EMPs to support wound
      healing and new periodontal tissue formation.

PMID- 18724845
TI  - Regeneration of periodontal tissues: combinations of barrier membranes and
      grafting materials - biological foundation and preclinical evidence: a systematic
      review.
AB  - BACKGROUND: Regenerative periodontal therapy aims to predictably restore the
      tooth's supporting periodontal tissues and should result in formation of a new
      connective tissue attachment (i.e. new cementum with inserting periodontal
      ligament fibres) and new alveolar bone. Histologic evidence from preclinical
      models has demonstrated periodontal regeneration following treatment with barrier
      membranes, various types of grafting materials or a combination thereof. However,
      it is still not clear to what extent a combination of barrier membranes and
      grafting materials may additionally enhance the regeneration process compared
      with barrier membranes alone, grafting materials alone or open flap debridement.
      OBJECTIVES: To review with a systematic approach all preclinical (i.e. animal)
      studies presenting histologic support for periodontal regeneration using the
      combination of barrier membranes and grafting materials. MATERIAL AND METHODS:
      Based on a focused question, an electronic and manual search was conducted for
      animal studies presenting histological data for the effect of the combined use of
      barrier membranes and grafting materials on the treatment of periodontal defects.
      A systematic approach was followed by two independent reviewers including
      eligibility criotateria for study inclusion, outcome measures determination,
      screening method, data extraction, data synthesis and drawing of conclusions.
      RESULTS: Ten papers completely fulfilling the inclusion criteria were selected.
      All relevant data from the selected papers were extracted and recorded in
      separate tables according to the types of periodontal defects treated (i.e. supra
      alveolar defects, intrabony defects, furcation defects and fenestration defects)
      with the combination of barrier membranes and grafting materials. Most studies
      have demonstrated periodontal regeneration following the combination approach.
      Most studies demonstrated superior histologic healing following the combination
      of barrier membranes and grafting materials than following open flap debridement.
      Histologically superior healing following the combination of barrier membranes
      and grafting materials when compared with barrier membranes alone or grafting
      materials alone were only obtained in non-contained two wall intrabony and
      supraalveolar defects. CONCLUSION: Within its limits the present analysis
      indicates that: (a) The combination of barrier membranes and grafting materials
      may result in histological evidence of periodontal regeneration, predominantly
      bone repair. (b) No additional benefits of combination treatments were detected
      in models of three wall intrabony, Class II furcation or fenestration defects.
      (c) In supra-alveolar and two wall intrabony (missing buccal wall) defect models
      of periodontal regeneration, the additional use of a grafting material gave
      superior histological results of bone repair to barrier membranes alone. (d) In
      one study using a supra-alveolar model, combined graft and barrier membrane gave
      a superior result to graft alone.

PMID- 18724846
TI  - Clinical outcomes with bioactive agents alone or in combination with grafting or
      guided tissue regeneration.
AB  - AIM: The purpose of the present review was to determine the clinical effect of
      the use of bioactive agents (BAs) for the treatment of intra-osseous and
      furcation defects. MATERIAL AND METHODS: The effectiveness of the BAs was
      evaluated when used in addition to open flap debridement either alone or in
      association with grafts and/or guided tissue regeneration (GTR). Among the
      included agents, recombinant human platelet-derived growth factor-BB (rhPDGF-BB),
      platelet-rich plasma (PRP), commercially available enamel matrix derivative
      (cEMD) and peptide P-15 (P-15) have been clinically tested for treating
      periodontal defects. RESULTS AND CONCLUSIONS: The results of the present review
      indicate that: (1) cEMD either alone or in combination with grafts can be
      effectively used to treat intra-osseous defects and the clinical results appear
      to be stable long term; (2) the additional use of a graft seems to enhance the
      clinical outcome of cEMD; (3) the combined use of rhPDGF-BB and P-15 with a graft
      biomaterial has shown beneficial effects in intra-osseous defects; (4)
      contrasting results were reported for PRP and graft combinations; and (5) limited
      evidence supports the use of BAs either alone or in association with graft/GTR
      for the treatment of furcation defects.

PMID- 18724847
TI  - Treatment of gingival recession with coronally advanced flap procedures: a
      systematic review.
AB  - BACKGROUND: The treatment of buccal gingival recessions is a common requirement
      due to aesthetic concern or root sensitivity. The aim of this manuscript was to
      systematically review the literature on coronally advanced flap (CAF) alone or in
      combination with tissue grafts, barrier membranes (BM), enamel matrix derivative
      (EMD) or other material for treating gingival recession. MATERIAL AND METHODS:
      Randomized clinical trials on treatment of Miller Class I and II gingival
      recessions with at least 6 months of follow-up were identified. Data sources
      included electronic databases and hand-searched journals. The primary outcome
      variable was complete root coverage (CRC). The secondary outcome variables were
      recession reduction, clinical attachment gain, keratinized tissue gain, aesthetic
      satisfaction, root sensitivity, post-operative patient pain and complications.
      RESULTS: A total of 794 Miller Class I and II gingival recessions in 530 patients
      from 25 RCTs were evaluated in this systematic review. CAF was associated with
      mean recession reduction and CRC. The addition of connective tissue graft (CTG)
      or EMD enhanced the clinical outcomes of CAF in terms of CRC, while BM did not.
      The results with respect to the adjunctive use of acellular dermal matrix were
      controversial. CONCLUSIONS: CTG or EMD in conjunction with CAF enhances the
      probability of obtaining CRC in Miller Class I and II single gingival recessions.

PMID- 18724848
TI  - Soft tissue management at implant sites.
AB  - BACKGROUND: Dental implants are widely used to replace lost teeth. It was
      suggested that surgical manipulation/augmentation of peri-implant soft tissue may
      be beneficial to increase the width/thickness of keratinized tissue (KT) and to
      enhance aesthetic outcomes of implant therapy. The aim of this paper was to
      provide a narrative review of the literature concerning soft tissue management at
      implant sites. MATERIAL AND METHODS: Clinical studies were identified with both
      medline and hand searches. Three topics were considered in this review: (i) the
      significance of KT at implant sites, (ii) the surgical techniques to increase KT
      and (iii) soft tissue stability around implants. RESULTS: Several papers
      concerning soft tissue management at implant sites were identified, mainly expert
      opinions, case reports and case series. In addition, a systematic review was
      selected. Generally, the level of evidence was weak. So far, literature analysis
      showed that (i) the width of KT did not influence the survival rate of dental
      implants; (ii) there is no evidence to recommend a specific technique to
      preserve/augment KT; and (iii) factors including bone level, KT and implant
      features have not been shown to be associated with future mucosal recession
      around dental implants. CONCLUSION: Although scientific evidence in most part is
      lacking, soft tissue augmentation at implant sites may need to be considered in
      some clinical situations.

PMID- 18724849
TI  - Advances in bone augmentation to enable dental implant placement: Consensus
      Report of the Sixth European Workshop on Periodontology.
AB  - BACKGROUND: Bone augmentation procedures to enable dental implant placement are
      frequently performed in practice. METHODS: In this session the European Workshop
      on Periodontology discussed the evidence in support of the procedures and
      examined both adverse events and implant performance in the augmented bone. While
      the available evidence improved both in quantity and quality since previous
      workshops the conclusions that could be drawn were limited by elements of design
      and/or reporting that are amenable to improvement. RESULTS: With regards to
      lateral bone augmentation, a sizable body of evidence supports its use to enable
      dental implant placement. The group recognized the potential for vertical ridge
      augmentation procedures to allow implant placement in clinical practice but
      questioned the applicability of these data to a wider array of operators and
      clinical settings. With regards to sinus floor augmentation, perforation of the
      sinus membrane, graft infection and graft loss resulting in inability of implant
      placement were the major reported adverse events. In cases with <6 mm of residual
      bone height, 17% of subjects experienced implant loss in the first 3 years
      following lateral window augmentation. After trans-alveolar sinus floor
      augmentation 11% of subjects experienced implant loss over 3 years. Significant
      research activity (both pre-clinical and clinical) was identified in the area of
      growth factors-induced bone augmentation. Initial clinical trials support the
      potential of BMP-2. CONCLUSIONS: Clinically, the consensus highlighted that bone
      augmentation procedures can fail and that implants placed in these areas do not
      necessarily enjoy the high long-term survival rates of dental implants placed in
      pristine sites. The consensus emphasized the research need to answer questions
      on: (i) long-term performance of dental implants placed in augmented bone; (ii)
      the clinical performance of dental implants placed in augmented or pristine
      sites; and (iii) the clinical benefits of bone augmentation with respect to
      alternative treatments.

PMID- 18724850
TI  - Clinical outcomes of implants following lateral bone augmentation: systematic
      assessment of available options (barrier membranes, bone grafts, split
      osteotomy).
AB  - OBJECTIVE: To compare the clinical outcomes related to implants following lateral
      augmentation procedures (GBR, bone grafts, split osteotomy) with implants placed
      in pristine sites. MATERIAL AND METHODS: A systematic review of all prospective
      studies of implants placed simultaneously or as a second surgery following
      lateral augmentation compared with implants placed in pristine bone with 6 months
      of loading was performed. RESULTS: From 435 potentially relevant publications,
      125 full-text publications were screened and four were identified as fulfilling
      the inclusion criteria. Three studies compared implants placed with simultaneous
      GBR or with a bone substitute and one with autogenous bone graft as a staged
      procedure. The implant survival at the augmented sites irrespective of the
      procedure used varied from 91.7% to 100% and from 93.2% to 100% at the control
      sites for a period between 12 and 59.1 months. CONCLUSIONS: Within the limits of
      the systematic review there was evidence that the evaluated augmentation
      techniques result in similar implant survival between augmented and pristine
      sites. The small number of retrieved studies fulfilling the inclusion criteria
      limited the conclusions regarding the success of the augmentation and its effect
      on the survival of the implants. Properly designed randomized controlled clinical
      trials on this topic are needed.

PMID- 18724851
TI  - Clinical outcomes of vertical bone augmentation to enable dental implant
      placement: a systematic review.
AB  - BACKGROUND: This review addressed the focused question of what is the
      predictability of vertical ridge augmentation techniques for patients, who were
      diagnosed with insufficient alveolar bone volume for the placement of dental
      implants. MATERIAL AND METHODS: A systematic online review of three main
      databases was performed between 1966 and 1 November 2007. Four groups of vertical
      bone augmentation techniques have been identified and evaluated: (1) guided bone
      regeneration, (2) distraction osteogenesis, (3) onlay bone grafting, and (4) an
      array of different techniques. Data extraction was based on the following
      outcomes: (a) success and failure rate of the procedure (vertical bone
      gain/loss), (b) complication rate of the procedure, and (c) implant survival,
      success and failure rate. RESULTS: The initial search identified 189 papers from
      the electronic database. The review produced seven papers for GBR, 13 reporting
      distraction osteogenesis, five for onlay bone grafting and three describing
      different techniques. CONCLUSIONS: For the concept of vertical ridge augmentation
      to enable dental implant placement, there are clinical and histological data
      supporting its potential use. Given the confined number of investigators using
      these techniques and the low number of patient treatments reported in the
      literature, the generalizability of this approach is limited at this time.

PMID- 18724852
TI  - A systematic review of the success of sinus floor elevation and survival of
      implants inserted in combination with sinus floor elevation.
AB  - OBJECTIVES: The objectives of this systematic review were to assess the survival
      rate of grafts and implants placed with sinus floor elevation. MATERIAL AND
      METHODS: An electronic search was conducted to identify studies on sinus floor
      elevation, with a mean follow-up time of at least 1 year after functional
      loading. RESULTS: The search provided 839 titles. Full-text analysis was
      performed for 175 articles resulting in 48 studies that met the inclusion
      criteria, reporting on 12,020 implants. Meta-analysis indicated an estimated
      annual failure rate of 3.48% [95% confidence interval (CI): 2.48%-4.88%]
      translating into a 3-year implant survival of 90.1% (95% CI: 86.4%-92.8%).
      However, when failure rates was analyzed on the subject level, the estimated
      annual failure was 6.04% (95% CI: 3.87%-9.43%) translating into 16.6% (95% CI:
      10.9%-24.6%) of the subjects experiencing implant loss over 3 years. CONCLUSION:
      The insertion of dental implants in combination with maxillary sinus floor
      elevation is a predictable treatment method showing high implant survival rates
      and low incidences of surgical complications. The best results (98.3% implant
      survival after 3 years) were obtained using rough surface implants with membrane
      coverage of the lateral window.

PMID- 18724853
TI  - A systematic review of the success of sinus floor elevation and survival of
      implants inserted in combination with sinus floor elevation. Part II:
      transalveolar technique.
AB  - OBJECTIVES: The objectives of this systematic review were to assess the survival
      rate of implants placed in sites with transalveolar sinus floor elevation.
      MATERIAL AND METHODS: An electronic search was conducted to identify prospective
      and retrospective cohort studies on transalveolar sinus floor elevation, with a
      mean follow-up time of at least 1 year after functional loading. Failure and
      complication rates were analyzed using random-effects Poisson regression models
      to obtain summary estimates/ year proportions. RESULTS: The search provided 849
      titles. Full-text analysis was performed for 176 articles, resulting in 19
      studies that met the inclusion criteria. Meta-analysis of these studies indicated
      an estimated annual failure rate of 2.48% (95% confidence interval (95% CI): 1.37
      4.49%) translating to an estimated survival rate of 92.8% (95% CI): 87.4-96.0%)
      for implants placed in transalveolarly augmented sinuses, after 3 years in
      function. Furthermore, subject-based analysis revealed an estimated annual
      failure of 3.71% (95% CI: 1.21-11.38%), translating to 10.5% (95% CI: 3.6-28.9%)
      of the subjects experiencing implant loss over 3 years. CONCLUSION: Survival
      rates of implants placed in transalveolar sinus floor augmentation sites are
      comparable to those in non-augmented sites. This technique is predictable with a
      low incidence of complications during and post-operatively.

PMID- 18724854
TI  - Assessment of the potential of growth factors for localized alveolar ridge
      augmentation: a systematic review.
AB  - OBJECTIVE: To systematically assess the literature regarding the clinical,
      histological, and radiographic outcome of bone morphogenetic proteins (BMP-2, BMP
      7), growth/differentiation factor-5 (GDF-5), platelet-derived growth factor
      (PDGF), and parathyroid hormone (PTH) for localized alveolar ridge augmentation.
      MATERIAL AND METHODS: Five separate Medline searches were performed in duplicate
      for human and animal studies, respectively. The primary outcome of the included
      studies was bone regeneration of localized alveolar ridge defects or craniofacial
      defects. RESULTS: In six human studies, BMP-2 affected local bone augmentation
      with increasing volume for higher doses. A majority (43 of 45) of animal studies
      using BMP-2 showed a positive effect in favour of the growth factor (GF). In six
      of eight studies, a positive effect was associated with the use of BMP-7. Only
      one animal study was included for GDF-5 revealing statistically significantly
      higher bone volume. Regarding PDGF, statistically significantly higher bone
      volume was observed in five of 10 included studies. Four animal studies using PTH
      revealed statistically significantly more bone regeneration compared with
      controls. CONCLUSIONS: Differing levels and quantity of evidence were noted to be
      available for the GFs evaluated, revealing that BMP-2, BMP-7, GDF-5, PDGF, and
      PTH may stimulate local bone augmentation to various degrees. Human data for the
      potential of rhBMP-2 are supportive.

PMID- 18724855
TI  - Peri-implant diseases: Consensus Report of the Sixth European Workshop on
      Periodontology.
AB  - Issues related to peri-implant disease were discussed. It was observed that the
      most common lesions that occur, i.e. peri-implant mucositis and peri-implantitis
      are caused by bacteria. While the lesion of peri-implant mucositis resides in the
      soft tissues, peri-implantitis also affects the supporting bone. Peri-implant
      mucositis occurs in about 80% of subjects (50% of sites) restored with implants,
      and peri-implantitis in between 28% and 56% of subjects (12-40% of sites). A
      number of risk indicators were identified including (i) poor oral hygiene, (ii) a
      history of periodontitis, (iii) diabetes and (iv) smoking. It was concluded that
      the treatment of peri-implant disease must include anti-infective measures. With
      respect to peri-implant mucositis, it appeared that non-surgical mechanical
      therapy caused the reduction in inflammation (bleeding on probing) but also that
      the adjunctive use of antimicrobial mouthrinses had a positive effect. It was
      agreed that the outcome of non-surgical treatment of peri-implantitis was
      unpredictable. The primary objective of surgical treatment in peri-implantitis is
      to get access to the implant surface for debridement and decontamination in order
      to achieve resolution of the inflammatory lesion. There was limited evidence that
      such treatment with the adjunctive use of systemic antibiotics could resolve a
      number of peri-implantitis lesions. There was no evidence that so-called
      regenerative procedures had additional beneficial effects on treatment outcome.

PMID- 18724856
TI  - Definition and prevalence of peri-implant diseases.
AB  - OBJECTIVES: The aim of the current review was to describe the prevalence of peri
      implant diseases including peri-implant mucositis and peri-implantitis. MATERIAL
      AND METHODS: A MEDLINE search (PubMed) until December 2007 was conducted and
      different keywords related to the prevalence of peri-implant diseases were used.
      Cross-sectional and longitudinal studies including > or =50 implant-treated
      subjects exhibiting a function time of > or =5 years were considered. RESULTS AND
      CONCLUSION: The current review revealed that only a few studies provided data on
      the prevalence of peri-implant diseases. Cross-sectional studies on implant
      treated subjects are rare and data from only two study samples were available.
      Peri-implant mucositis occurred in approximately 80% of the subjects and in 50%
      of the implants. Peri-implantitis was found in 28% and > or =56% of subjects and
      in 12% and 43% of implant sites.

PMID- 18724857
TI  - Peri-implant diseases: diagnosis and risk indicators.
AB  - BACKGROUND: Peri-implant diseases include peri-implant mucositis, describing an
      inflammatory lesion of the peri-implant mucosa, and peri-implantitis, which also
      includes loss of supporting bone. METHODS: A literature search of the Medline
      database (Ovid), up to 21 January 2008 was carried out using a systematic
      approach, in order to review the evidence for diagnosis and the risk indicators
      for peri-implant diseases. RESULTS: Experimental and clinical studies have
      identified various diagnostic criteria including probing parameters, radiographic
      assessment and peri-implant crevicular fluid and saliva analyses. Cross-sectional
      analyses have investigated potential risk indicators for peri-implant disease
      including poor oral hygiene, smoking, history of periodontitis, diabetes, genetic
      traits, alcohol consumption and implant surface. There is evidence that probing
      using a light force (0.25 N) does not damage the peri-implant tissues and that
      bleeding on probing (BOP) indicates presence of inflammation in the peri-implant
      mucosa. The probing depth, the presence of BOP, and suppuration should be
      assessed regularly for the diagnosis of peri-implant diseases. Radiographs are
      required to evaluate supporting bone levels around implants. The review
      identified strong evidence that poor oral hygiene, a history of periodontitis and
      cigarette smoking, are risk indicators for peri-implant disease. Future
      prospective studies are required to confirm these factors as true risk factors.

PMID- 18724858
TI  - Non-surgical treatment of peri-implant mucositis and peri-implantitis: a
      literature review.
AB  - OBJECTIVES: To review the literature on non-surgical treatment of peri-implant
      mucositis and peri-implantitis. MATERIAL AND METHODS: A search of PubMed and The
      Cochrane Library of the Cochrane Collaboration (CENTRAL) as well as a hand search
      of articles were conducted. Publications and articles accepted for publication up
      to November 2007 were included. RESULTS: Out of 437 studies retrieved a total of
      24 studies were selected for the review. Thus the available evidence for non
      surgical treatment of peri-implant mucositis and peri-implantitis is scarce.
      CONCLUSIONS: It was observed that mechanical non-surgical therapy could be
      effective in the treatment of peri-implant mucositis lesions. Furthermore, the
      adjunctive use of antimicrobial mouth rinses enhanced the outcome of mechanical
      therapy of such mucositis lesions. In peri-implantitis lesions non-surgical
      therapy was not found to be effective. Adjunctive chlorhexidine application had
      only limited effects on clinical and microbiological parameters. However,
      adjunctive local or systemic antibiotics were shown to reduce bleeding on probing
      and probing depths. Minor beneficial effects of laser therapy on peri-implantitis
      have been shown; this approach needs to be further evaluated. There is a need for
      randomized-controlled studies evaluating treatment models of non-surgical therapy
      of peri-implant mucositis and peri-implantitis.

PMID- 18724859
TI  - Surgical treatment of peri-implantitis.
AB  - OBJECTIVES: To review the literature on surgical treatment of peri-implantitis.
      MATERIAL AND METHODS: A search of PubMed and as well as a hand search of articles
      were conducted. Publications and articles accepted for publication up to November
      2007 were included. RESULTS: A total of 43 studies were selected for the review.
      Only 13 of these were studies in humans and only one study directly addressed
      disease resolution. Thus the available evidence for surgical treatment of peri
      implantitis is extremely limited. ANIMAL STUDIES: Re-osseointegration can occur
      on previously contaminated surfaces. The surface characteristics are decisive for
      regeneration and re-osseointegration. No single surface decontamination method
      appears to be distinctly superior. Open debridement with surface decontamination
      can achieve resolution. HUMAN STUDIES: Access surgery has been investigated in
      one study demonstrating that resolution occurred in 58% of the lesions. No single
      method of surface decontamination (chemical agents, air abrasives and lasers) was
      found to be superior. The use of regenerative procedures such as bone graft
      techniques with or without the use of barrier membranes has been reported with
      various degrees of success. However, it must be stressed that such techniques do
      not address disease resolution but rather merely attempt to fill the osseous
      defect.

PMID- 18724860
TI  - Periodontal diseases and health: Consensus Report of the Sixth European Workshop
      on Periodontology.
AB  - INTRODUCTION: The remit of this group was to update the knowledge base on
      periodontal diseases and health. MATERIAL AND METHODS: The literature was
      systematically searched and critically reviewed in five specific topics. RESULTS:
      Prevalence of periodontitis: The data suggest a trend towards a lower prevalence
      of periodontitis in recent years. Adverse pregnancy outcome: The findings
      indicate a likely association between periodontal disease and an increased risk
      of adverse pregnancy outcomes. There is no evidence that treating periodontal
      disease decreases the rate of adverse pregnancy outcomes. Prevalence and
      distribution of periodontal pathogens: Genetic analysis of bacteria has
      demonstrated an unanticipated diversity within species. Carriage rates and
      particular subsets of these species vary between ethnic groups. Few of these
      differences can be related to differences in disease prevalence. Diabetes
      mellitus: Evidence on the association supports the concept of increased severity
      but not extent of periodontitis in subjects with poorly controlled diabetes. It
      is inconclusive that periodontal treatment results in improved metabolic control.
      Cardiovascular diseases: Evidence suggests that having periodontitis contributes
      to the total infectious and inflammation burden and may contribute to
      cardiovascular events and stroke in susceptible subjects. The impact of
      periodontal therapy must be further investigated.

PMID- 18724861
TI  - Has the prevalence of periodontitis changed during the last 30 years?
AB  - AIM: This paper reviews global trends in the change in prevalence of
      periodontitis over the last 30 years. MATERIAL AND METHODS: The epidemiology of
      periodontal disease is briefly reviewed together with the current classification
      system and the clinical and radiographic diagnostic methodology in periodontal
      disease. RESULTS: This review identifies the very limited number of studies that
      provide prevalence data over time, and this data is discussed in comparison with
      those stemming from a few corresponding studies from countries outside Europe.
      CONCLUSIONS: The data indicate a possible trend of a lower prevalence of
      periodontitis in recent years.

PMID- 18724862
TI  - Prevalence and distribution of principal periodontal pathogens worldwide.
AB  - BACKGROUND: Detailed genetic analysis of bacteria has demonstrated an
      unanticipated genetic diversity within species, which often reveals evolutionary
      lineages that are disproportionately associated with infection. There is evidence
      that some evolutionary lineages of bacteria have adapted to particular ethnic
      groups. AIM: This review analyzes to what extent observed differences in
      periodontal disease prevalence among ethnically or geographically distinct
      populations may be explained by restricted host adaptation of clones of principal
      periodontal pathogens. RESULTS: Carriage rates of several putative periodontal
      pathogens and particular subsets of these species vary between ethnic groups. Few
      of these differences can, with the limited information available, be directly
      related to differences in periodontal disease prevalence. Asian populations are
      regularly colonized with Actinobacillus actinomycetemcomitans serotype c with
      questionable pathogenic potential. Conversely, the JP2 clone of A.
      actinomycetemcomitans has enhanced virulence and causes significantly higher
      prevalence of aggressive periodontitis in adolescents whose descent can be traced
      back to the Mediterranean and Western parts of Africa. Some genetically distinct
      types of Porphyromonas gingivalis are more associated with disease than others,
      but additional work is required to relate this to clinical differences.
      CONCLUSIONS: Studies that take into account differences linked to the genetics of
      both patients and potential pathogens are likely to give better insight into the
      aetiology of periodontal diseases.

PMID- 18724863
TI  - Cardiovascular disease and periodontitis: an update on the associations and risk.
AB  - BACKGROUND: Associations between periodontitis and cardiovascular diseases have
      been recognized. MATERIAL AND METHODS: New literature since the last European
      Workshop on Periodontology has been reviewed. RESULTS: The lack of reliable
      epidemiological data on disease prevalence makes an assessment of the
      associations and risks between periodontitis and cardiovascular diseases
      difficult. Two recent meta-analysis reports have identified associations between
      periodontitis and cardiovascular diseases (odds ratios: 1.1-2.2). Different
      surrogate markers for both disease entities, including serum biomarkers, have
      been investigated. Brachial artery flow-mediated dilatation, and carotid intima
      media thickness have in some studies been linked to periodontitis. Studies are
      needed to confirm early results of improvements of such surrogate markers
      following periodontal therapy. While intensive periodontal therapy may enhance
      inflammatory responses and impair vascular functions, studies are needed to
      assess the outcome of periodontal therapies in subjects with confirmed
      cardiovascular conditions. Tooth eradication may also reduce the systemic
      inflammatory burden of individuals with severe periodontitis. The role of
      confounders remain unclear. CONCLUSIONS: Periodontitis may contribute to
      cardiovascular disease and stroke in susceptible subjects. Properly powered
      longitudinal case-control and intervention trials are needed to identify how
      periodontitis and periodontal interventions may have an impact on cardiovascular
      diseases.

PMID- 18724865
TI  - Effects of diabetes mellitus on periodontal and peri-implant conditions: update
      on associations and risks.
AB  - OBJECTIVES: To review the evidence for the association between diabetes and
      periodontal and peri-implant conditions and the impact of periodontal therapy in
      subjects with diabetes. MATERIAL AND METHODS: A search of MEDLINE-PubMed was
      performed up to and including December 2007. The search was limited to clinical
      studies published in English. Publications on animal studies were excluded. The
      selection criteria included all levels of available evidence. RESULTS: Evidence
      on the association between diabetes and periodontitis supports the concept of
      increased severity but not extent of periodontitis in subjects with poorly
      controlled diabetes. Subjects with controlled diabetes do not show an increase in
      extent and severity of periodontitis. Periodontitis is associated with poor
      glycaemic control and diabetes-related complications. It is inconclusive that
      periodontal therapy with or without the use of antibiotics results in
      improvements of glycaemic control and of markers of systemic inflammation.
      Evidence is lacking to indicate that implant therapy in subjects with diabetes
      yields long-term outcomes comparable with those of non-diabetic subjects.
      CONCLUSIONS: Poorly controlled diabetes may be considered a risk factor for
      increased severity of periodontitis. The effects of periodontal therapy on
      glycaemic control and systemic inflammation is not proven beyond doubt and need
      to be confirmed in large-scale randomized-controlled clinical trials.

PMID- 18724864
TI  - A critical assessment of adverse pregnancy outcome and periodontal disease.
AB  - BACKGROUND: Pre-term birth is a major cause of infant mortality and morbidity
      that has considerable societal, medical, and economic costs. The rate of pre-term
      birth appears to be increasing world-wide and efforts to prevent or reduce its
      prevalence have been largely unsuccessful. AIM: To review the literature for
      studies investigating periodontal disease as a possible risk factor for pre-term
      birth and adverse pregnancy outcomes. MAIN FINDINGS AND CONCLUSION: Variability
      among studies in definitions of periodontal disease and adverse pregnancy
      outcomes as well as widespread inadequate control for confounding factors and
      possible effect modification make it difficult to base meaningful conclusions on
      published data. However, while there are indications of an association between
      periodontal disease and increased risk of adverse pregnancy outcome in some
      populations, there is no conclusive evidence that treating periodontal disease
      improves birth outcome. Based on a critical qualitative review, available
      evidence from clinical trials indicates that, although non-surgical mechanical
      periodontal treatment in the second trimester of pregnancy is safe and effective
      in reducing signs of maternal periodontal disease, it does not reduce the rate of
      pre-term birth. Clinical trials currently underway will further clarify the
      potential role of periodontal therapy in preventing adverse birth outcomes.
      Regardless of the outcomes of these trials, it is recommended that large,
      prospective cohort studies be conducted to assess risk for adverse pregnancy
      outcome in populations with periodontal disease. It is critical that periodontal
      exposure and adverse birth outcomes be clearly defined and the many potential
      confounding factors and possible effect modifiers for adverse pregnancy outcome
      be controlled in these studies. If periodontal disease is associated with higher
      risk of adverse pregnancy outcome in these specific populations, large
      multicenter randomized-controlled trials will be needed to determine if
      prevention or treatment of periodontal disease, perhaps combined with other
      interventions, has an effect on adverse pregnancy outcome in these women.

PMID- 18724866
TI  - Malaria incidence in Limpopo Province, South Africa, 1998-2007.
AB  - BACKGROUND: Malaria is endemic in the low-altitude areas of the northern and
      eastern parts of South Africa with seasonal transmission. The aim of this
      descriptive study is to give an overview of the malaria incidence and mortality
      in Limpopo Province for the seasons 1998-1999 to 2006-2007 and to detect trends
      over time and place. METHODS: Routinely collected data on diagnosed malaria cases
      and deaths were available through the provincial malaria information system. In
      order to calculate incidence rates, population estimates (by sex, age and
      district) were obtained from Statistics South Africa. The Chi squared test for
      trend was used to detect temporal trends in malaria incidence over the seasons,
      and a trend in case fatality rate (CFR) by age group. The Chi squared test was
      used to calculate differences in incidence rate and CFR between both sexes and in
      incidence by age group. RESULTS: In total, 58,768 cases of malaria were reported,
      including 628 deaths. The mean incidence rate was 124.5 per 100,000 person-years
      and the mean CFR 1.1% per season. There was a decreasing trend in the incidence
      rate over time (p < 0.001), from 173.0 in 1998-1999 to 50.9 in 2006-2007. The CFR
      was fairly stable over the whole period. The mean incidence rate in males was
      higher than in females (145.8 versus 105.6; p < 0.001); the CFR (1.1%) was
      similar for both sexes. The incidence rate was lowest in 0-4 year olds (78.3), it
      peaked at the ages of 35-39 years (172.8), and decreased with age from 40 years
      (to 84.4 for those > or = 60 years). The CFR increased with increasing age (to
      3.8% for those > or = 60 years). The incidence rate varied widely between
      districts; it was highest in Vhembe (328.2) and lowest in Sekhukhune (5.5).
      CONCLUSION: Information from this study may serve as baseline data to determine
      the course and distribution of malaria in Limpopo province over time. In the
      study period there was a decreasing trend in the incidence rate. Furthermore, the
      study addresses the need for better data over a range of epidemic-prone settings.

PMID- 18724867
TI  - Variable size computer-aided detection prompts and mammography film reader
      decisions.
AB  - INTRODUCTION: The purpose of the present study was to investigate the effect of
      computer-aided detection (CAD) prompts on reader behaviour in a large sample of
      breast screening mammograms by analysing the relationship of the presence and
      size of prompts to the recall decision. METHODS: Local research ethics committee
      approval was obtained; informed consent was not required. Mammograms were
      obtained from women attending routine mammography at two breast screening centres
      in 1996. Films, previously double read, were re-read by a different reader using
      CAD. The study material included 315 cancer cases comprising all screen-detected
      cancer cases, all subsequent interval cancers and 861 normal cases randomly
      selected from 10,267 cases. Ground truth data were used to assess the efficacy of
      CAD prompting. Associations between prompt attributes and tumour features or
      reader recall decisions were assessed by chi-squared tests. RESULTS: There was a
      highly significant relationship between prompting and a decision to recall for
      cancer cases and for a random sample of normal cases (P < 0.001). Sixty-four per
      cent of all cases contained at least one CAD prompt. In cancer cases, larger
      prompts were more likely to be recalled (P = 0.02) for masses but there was no
      such association for calcifications (P = 0.9). In a random sample of 861 normal
      cases, larger prompts were more likely to be recalled (P = 0.02) for both mass
      and calcification prompts. Significant associations were observed with prompting
      and breast density (p = 0.009) for cancer cases but not for normal cases (P =
      0.05). CONCLUSIONS: For both normal cases and cancer cases, prompted mammograms
      were more likely to be recalled and the prompt size was also associated with a
      recall decision.

PMID- 18724868
TI  - Interfield dysbalances in research input and output benchmarking: visualisation
      by density equalizing procedures.
AB  - BACKGROUND: Historical, social and economic reasons can lead to major differences
      in the allocation of health system resources and research funding. These
      differences might endanger the progress in diagnostic and therapeutic approaches
      of socio-economic important diseases. The present study aimed to assess different
      benchmarking approaches that might be used to analyse these disproportions.
      Research in two categories was analysed for various output parameters and
      compared to input parameters. Germany was used as a high income model country.
      For the areas of cardiovascular and respiratory medicine density equalizing
      mapping procedures visualized major geographical differences in both input and
      output markers. RESULTS: An imbalance in the state financial input was present
      with 36 cardiovascular versus 8 respiratory medicine state-financed full clinical
      university departments at the C4/W3 salary level. The imbalance in financial
      input is paralleled by an imbalance in overall quantitative output figures: The
      36 cardiology chairs published 2708 articles in comparison to 453 articles
      published by the 8 respiratory medicine chairs in the period between 2002 and
      2006. This is a ratio of 75.2 articles per cardiology chair and 56.63 articles
      per respiratory medicine chair. A similar trend is also present in the
      qualitative measures. Here, the 2708 cardiology publications were cited 48337
      times (7290 times for respiratory medicine) which is an average citation of 17.85
      per publication vs. 16.09 for respiratory medicine. The average number of
      citations per cardiology chair was 1342.69 in contrast to 911.25 citations per
      respiratory medicine chair. Further comparison of the contribution of the 16
      different German states revealed major geographical differences concerning
      numbers of chairs, published items, total number of citations and average
      citations. CONCLUSION: Despite similar significances of cardiovascular and
      respiratory diseases for the global burden of disease, large input and output
      imbalances have been revealed in the present study which point to a need for
      changes in funding policies. The present study supplies data that could be used
      for decision making in the field of health systems funding.

PMID- 18724869
TI  - Detection of genome-wide polymorphisms in the AT-rich Plasmodium falciparum
      genome using a high-density microarray.
AB  - BACKGROUND: Genetic mapping is a powerful method to identify mutations that cause
      drug resistance and other phenotypic changes in the human malaria parasite
      Plasmodium falciparum. For efficient mapping of a target gene, it is often
      necessary to genotype a large number of polymorphic markers. Currently, a
      community effort is underway to collect single nucleotide polymorphisms (SNP)
      from the parasite genome. Here we evaluate polymorphism detection accuracy of a
      high-density 'tiling' microarray with 2.56 million probes by comparing single
      feature polymorphisms (SFP) calls from the microarray with known SNP among
      parasite isolates. RESULTS: We found that probe GC content, SNP position in a
      probe, probe coverage, and signal ratio cutoff values were important factors for
      accurate detection of SFP in the parasite genome. We established a set of SFP
      calling parameters that could predict mSFP (SFP called by multiple overlapping
      probes) with high accuracy (> or = 94%) and identified 121,087 mSFP genome-wide
      from five parasite isolates including 40,354 unique mSFP (excluding those from
      multi-gene families) and approximately 18,000 new mSFP, producing a genetic map
      with an average of one unique mSFP per 570 bp. Genomic copy number variation
      (CNV) among the parasites was also cataloged and compared. CONCLUSION: A large
      number of mSFP were discovered from the P. falciparum genome using a high-density
      microarray, most of which were in clusters of highly polymorphic genes at
      chromosome ends. Our method for accurate mSFP detection and the mSFP identified
      will greatly facilitate large-scale studies of genome variation in the P.
      falciparum parasite and provide useful resources for mapping important parasite
      traits.

PMID- 18724870
TI  - Signal transduction around thymic stromal lymphopoietin (TSLP) in atopic asthma.
AB  - Thymic stromal lymphopoietin (TSLP), a novel interleukin-7-like cytokine,
      triggers dendritic cell-mediated inflammatory responses ultimately executed by T
      helper cells of the Th2 subtype. TSLP emerged as a central player in the
      development of allergic symptoms, especially in the airways, and is a prime
      regulatory cytokine at the interface of virus- or antigen-exposed epithelial
      cells and dendritic cells (DCs). DCs activated by epithelium-derived TSLP can
      promote naive CD4+ T cells to adopt a Th2 phenotype, which in turn recruite
      eosinophilic and basophilic granulocytes as well as mast cells into the airway
      mucosa. These different cells secrete inflammatory cytokines and chemokines
      operative in inducing an allergic inflammation and atopic asthma. TSLP is, thus,
      involved in the control of both an innate and an adaptive immune response. Since
      TSLP links contact of allergen with the airway epithelium to the onset and
      maintainance of the asthmatic syndrome, defining the signal transduction
      underlying TSLP expression and function is of profound interest for a better
      understandimg of the disease and for the development of new therapeutics.

PMID- 18724871
TI  - Insertion polymorphisms of SINE200 retrotransposons within speciation islands of
      Anopheles gambiae molecular forms.
AB  - BACKGROUND: SINEs (Short INterspersed Elements) are homoplasy-free and co
      dominant genetic markers which are considered to represent useful tools for
      population genetic studies, and could help clarifying the speciation processes
      ongoing within the major malaria vector in Africa, Anopheles gambiae s.s. Here,
      we report the results of the analysis of the insertion polymorphism of a nearly
      200 bp-long SINE (SINE200) within genome areas of high differentiation (i.e.
      "speciation islands") of M and S A. gambiae molecular forms. METHODS: A SINE-PCR
      approach was carried out on thirteen SINE200 insertions in M and S females
      collected along the whole range of distribution of A. gambiae s.s. in sub-Saharan
      Africa. Ten specimens each for Anopheles arabiensis, Anopheles melas, Anopheles
      quadriannulatus A and 15 M/S hybrids from laboratory crosses were also analysed.
      RESULTS: Eight loci were successfully amplified and were found to be specific for
      A. gambiae s.s.: 5 on 2L chromosome and one on X chromosome resulted monomorphic,
      while two loci positioned respectively on 2R (i.e. S200 2R12D) and X (i.e. S200
      X6.1) chromosomes were found to be polymorphic. S200 2R12D was homozygote for the
      insertion in most S-form samples, while intermediate levels of polymorphism were
      shown in M-form, resulting in an overall high degree of genetic differentiation
      between molecular forms (Fst = 0.46 p < 0.001) and within M-form (Fst = 0.46 p <
      0.001). The insertion of S200 X6.1 was found to be fixed in all M- and absent in
      all S-specimens. This led to develop a novel easy-to-use PCR approach to
      straightforwardly identify A. gambiae molecular forms. This novel approach allows
      to overcome the constraints associated with markers on the rDNA region commonly
      used for M and S identification. In fact, it is based on a single copy and
      irreversible SINE200 insertion and, thus, is not subjected to peculiar
      evolutionary patterns affecting rDNA markers, e.g. incomplete homogenization of
      the arrays through concerted evolution and/or mixtures of M and S IGS-sequences
      among the arrays of single chromatids. CONCLUSION: The approach utilized allowed
      to develop new easy-to-use co-dominant markers for the analysis of genetic
      differentiation between M and S-forms and opens new perspectives in the study of
      the speciation process ongoing within A. gambiae.

PMID- 18724872
TI  - Predictors of HIV infection and prevalence for syphilis infection among injection
      drug users in China: community-based surveys along major drug trafficking routes.
AB  - OBJECTIVE: To assess the predictors and prevalence of HIV infection among
      injection drug users in highly endemic regions along major drug trafficking
      routes in three Chinese provinces. METHODS: We enrolled participants using
      community outreach and peer referrals. Questionnaire-based interviews provided
      demographic, drug use, and sexual behavior information. HIV was tested via ELISA
      and syphilis by RPR. RESULTS: Of the 689 participants, 51.8% were HIV-infected,
      with persons living in Guangxi having significantly lower prevalence (16.4%) than
      those from Xinjiang and Yunnan (66.8% and 67.1%, respectively). Syphilis
      seropositivity was noted in 5.4%. Longer duration of IDU, greater awareness of
      HIV transmission routes, and living in Xinjiang or Yunnan were associated with
      HIV seropositivity on multivariable analysis. Independent risk factors differed
      between sites. In Guangxi, being male and having a longer duration of IDU were
      independent risk factors for HIV infection; in Xinjiang, older age and sharing
      needles and/or syringes were independent factors; in Yunnan, more frequent drug
      injection, greater awareness of HIV transmission routes, and higher income were
      independent predictors of HIV seropositivity. CONCLUSION: Prevalence rates of HIV
      among IDUs in China are more than two out of three in some venues. Risk factors
      include longer duration of IDU and needle sharing. Also associated with HIV were
      factors that may indicate some success in education in higher risk persons, such
      as higher knowledge. A systemic community-level intervention with respect to
      evidenced-based, population-level interventions to stem the spread of HIV from
      IDU in China should include needle exchange, opiate agonist-based drug treatment,
      condom distribution along with promotion, and advocacy for community-based VCT
      with bridges to HIV preventive services and care.

PMID- 18724873
TI  - Stigmatising attitude of medical students towards a psychiatry label.
AB  - BACKGROUND: The aim of this study is to evaluate the effect of a psychiatric
      label attached to an apparently normal person on the attitude of final year
      medical students at a Nigerian university. METHODS: A questionnaire with sections
      on demographic information, a single-paragraph case description illustrating a
      normal person, a social distance scale and questions on expected burden was used
      to elicit responses from 144 final year medical students who have had previous
      exposure to psychiatric posting. The students consisted of two randomly assigned
      groups; group A received a case description with a psychiatric label attached
      while group B received the same case description but without a psychiatric label.
      RESULTS: A total of 68 (47.2%) of the students responded to the questionnaire
      with the attached psychiatric label, while 76 (52.8%) responded to the
      questionnaire without the attached label. There was no statistical difference in
      age (p = 0.187) and sex (p = 0.933) between the two groups of students. The
      students who responded to the questionnaire with the attached psychiatric label
      would not rent out their houses (p = 0.003), were unwilling to have as their next
      door neighbour (p = 0.004), or allow their sister to get married (p = 0.000) to
      the man depicted in the case description compared with those that responded to
      the questionnaire without label. This group also felt that the man would exhaust
      them both physically (p = 0.005) and emotionally (p = 0.021) in any relationship
      with him. CONCLUSION: These results strengthen the view that stigma attached to
      mental illness is not limited to the general public; medical students are also
      part of the stigmatizing world. There is, therefore, a need to incorporate issues
      concerning stigma and its reduction as a core component of the mental health
      curriculum of medical schools.

PMID- 18724874
TI  - Predictors of health-related quality of life in patients with colorectal cancer.
AB  - BACKGROUND: Most studies that have identified variables associated with the
      health-related quality of life (HRQL) of patients with colorectal cancer have
      been cross-sectional or included patients with other diagnoses. The objectives of
      this study were to identify predictors of HRQL in patients with colorectal cancer
      and interpret the clinical importance of the results. METHODS: We conducted a
      population-based longitudinal study of patients identified through three regions
      of the California Cancer Registry. Surveys were completed by 568 patients
      approximately 9 and 19 months post-diagnosis. Three HRQL outcomes from the
      Functional Assessment of Cancer Therapy--Colorectal (FACT-C) were evaluated:
      social/family well-being (SWB), emotional well-being (EWB) and the Trial Outcome
      Index (TOI), which is a colorectal cancer-specific summary measure of physical
      function and well-being. Sociodemographic, cancer/health, and healthcare
      variables were assessed in multivariable regression models. We computed the
      difference in predicted HRQL scores corresponding to a large difference in a
      predictor variable, defined as a 1 standard deviation difference for interval
      variables or the difference relative to the reference category for nominal
      variables. The effect of an explanatory variable on HRQL was considered
      clinically meaningful if the predicted score difference was at least as large as
      the minimally important difference. RESULTS: Common predictors of better TOI, SWB
      and EWB were better general health and factors related to better perceived
      quality of cancer care. Predictor variables in addition to general health and
      perceived quality of care were identified only for SWB. Being married/living as
      married was associated with better SWB, whereas being male or of Hispanic
      ethnicity was associated with worse SWB. Among the sociodemographic,
      cancer/health, and healthcare variables evaluated, only Hispanic ethnicity had a
      clinically meaningful effect on an HRQL outcome. CONCLUSION: Our findings,
      particularly the information on the clinical importance of predictor variables,
      can help clinicians identify patients who may be at risk for poor future HRQL.
      Potentially modifiable factors were related to perceived quality of cancer care;
      thus, future research should evaluate whether improving these factors improves
      HRQL.

PMID- 18724875
TI  - Anticipation of pain enhances the nociceptive transmission and functional
      connectivity within pain network in rats.
AB  - BACKGROUND: Expectation is a very potent pain modulator in both humans and
      animals. There is evidence that pain transmission neurons are modulated by
      expectation preceding painful stimuli. Nonetheless, few studies have examined the
      influence of pain expectation on the pain-related neuronal activity and the
      functional connectivity within the central nociceptive network. RESULTS: This
      study used a tone-laser conditioning paradigm to establish the pain expectation
      in rats, and simultaneously recorded the anterior cingulate cortex (ACC), the
      medial dorsal thalamus (MD), and the primary somatosensory cortex (SI) to
      investigate the effect of pain expectation on laser-induced neuronal responses.
      Cross-correlation and partial directed coherence analysis were used to determine
      the functional interactions within and between the recorded areas during
      nociceptive transmission. The results showed that under anticipation condition,
      the neuronal activity to the auditory cue was significantly increased in the ACC
      area, whereas those to actual noxious stimuli were enhanced in all the recorded
      areas. Furthermore, neuronal correlations within and between these areas were
      significantly increased under conditions of expectation compared to those under
      non-expectation conditions, indicating an enhanced synchronization of neural
      activity within the pain network. In addition, information flow from the medial
      (ACC and MD) to the lateral (SI cortex) pain pathway increased, suggesting that
      the emotion-related neural circuits may modulate the neuronal activity in the
      somatosensory pathway during nociceptive transmission. CONCLUSION: These results
      demonstrate that the nociceptive processing in both medial and lateral pain
      systems is modulated by the expectation of pain.

PMID- 18724876
TI  - The newest frontier: ethical landscapes in electronic healthcare.

PMID- 18724877
TI  - Bioethics, business ethics, and science: bioinformatics and the future of
      healthcare.

PMID- 18724878
TI  - Privacy issues in clinical genomic medicine, or Marcus Welby, M.D., meets the
      $1000 genome.

PMID- 18724879
TI  - "The cure is in hand"? The brave new world of handheld computers in medicine.

PMID- 18724880
TI  - Ethical challenges of telemedicine and telehealth.

PMID- 18724881
TI  - An analysis of factors underlying e-health disparities.

PMID- 18724882
TI  - An architecture for privacy in a networked health information environment.

PMID- 18724883
TI  - Organizational repertoires and rites in health information security.

PMID- 18724884
TI  - Net effect: professional and ethical challenges of medicine online.

PMID- 18724886
TI  - The use of aggression in primary school boys' decisions about inclusion in and
      exclusion from playground football games.
AB  - BACKGROUND: Sociometric studies have shown that some aggressive boys are popular,
      perceived as popular or cool, dominant, and central in the peer group (Estell,
      Cairns, Farmer, & Cairns, 2002; Milich & Landau, 1984; Prinstein & Cillessen,
      2003; Rodkin, Farmer, Pearl, & Van Acker, 2006). This is not predicted by social
      information processing (SIP) models which see aggression as socially incompetent,
      resulting from distorted understanding of the social world (e.g. Crick & Dodge,
      1994). However, sociologists of childhood have argued that some aggressive boys
      are popular because they use aggression to gain status and dominance, to
      undermine those of lower status, and to achieve hegemonic masculinity (Adler &
      Adler, 1998; Ferguson, 2000; Renold, 2007). AIMS: This study aims to connect
      psychological and sociological literatures, asking whether social processes of
      status formation contribute to the link between popularity and aggression
      identified sociometrically. SAMPLE: The paper describes case studies of three
      boys, aged between 8 and 10 years, attending a London primary school. METHODS:
      Sociometric data on liking, disliking, and aggression are combined with
      ethnographic and interview data for each case study. RESULTS: The data show that
      one way in which aggression aids popularity and dominance is through boys'
      strategic use of aggression to enforce decisions about inclusion and exclusion in
      desirable activities. It can be difficult for individual boys to achieve
      acceptance without resorting to aggression. CONCLUSIONS: The data provide support
      for sociological explanations of aggression in terms of status and inclusion, and
      challenge the SIP claim that aggressive children are socially incompetent and
      biased.

PMID- 18724887
TI  - Chronic pain syndrome associated with health anxiety: a qualitative thematic
      comparison between pain patients with high and low health anxiety.
AB  - OBJECTIVES: Based on the high prevalence of health anxiety among patients with
      chronic pain and the conceptual overlap between the diagnostic criteria for
      hypochondriasis and pain disorder, it has been suggested that the cognitive
      behavioural theory of severe and persistent health anxiety can be applied to
      understand the problems presented by a subgroup of chronic pain patients. This
      study aimed to provide qualitative data to complement the progress of the
      existing experimental research and theory development. DESIGN: A cross-sectional
      design with two groups was adopted. METHOD: In-depth semi-structured interviews
      were conducted with 60 chronic pain patients seeking medical treatment from a
      specialist clinic, and theoretical thematic analysis was performed on a subset of
      interview transcripts drawn from the five most health anxious and the five least
      health anxious of this sample. RESULTS: Five themes emerged from the analysis,
      and they concerned (1) pain appraisal, (2) pain preoccupation, (3) coping
      strategies, (4) self-identity, and (5) suicidal ideation. Differences were
      observed between the health anxious and non-health anxious pain patients
      consistently across all these themes. CONCLUSIONS: The phenomenological
      information both informs and supports the idea that the cognitive-behavioural
      model of health anxiety can be adapted for the understanding of and development
      of treatments for pain patients with health anxiety. The findings also challenge
      the common practice of 'lumping' pain patients into a single group and underline
      the importance of matching treatments to the patients' psychological
      characteristics.

PMID- 18724888
TI  - [Antiandrogenic effects of cypermethrin and beta-cypermethrin].
AB  - OBJECTIVE: To investigate the antiandrogenic activities of cypermethrin and beta
      cypermethrin in vitro and in vivo. METHODS: Transcriptional activation assay
      based on MDA-kb2 cell was used to determine the antiandrogenic effect of
      cypermethrin and beta-cypermethrin in vitro. The cells were treated by 10(-8),
      10(-7), 10(-6) and 10(-5) mol/L of cypermethrin and beta-cypermethrin with 1.0
      nmol/L DHT at the same time. The effects of antagonism towards the androgenic
      receptor were studied. In in vivo assays, Hershberger assay was used to determine
      the antiandrogenic activities of cypermethrin and beta-cypermethrin. Six-week-old
      castrated male SD rats were administered by cypermethrin (7, 21 and 63 mg/kg) and
      beta-cypermethrin (6, 18 and 54 mg/kg). After 7-day treatments, all rats were
      euthanized and androgen-responsive tissues were excised and weighed respectively.
      RESULTS: The in vitro experiments showed that 10(-6) and 10(-5) mol/L
      cypermethrin could inhibit significantly the antagonism activity towards the
      androgenic receptor of DHT. In in vivo tests, the weight of seminal vesicle,
      ventral prostate, dorsolateral prostate and preputial glands in the 63 mg/kg
      cypermethrin [(52.8 +/- 7.1), (42.4 +/- 8.9), (36.6 +/- 4.5) and (43.4 +/- 11.1)
      mg] decreased significantly compared with those in the control group. In 21 mg/kg
      cypermethrin treated group only the weights of ventral prostate and dorsolateral
      prostate decreased significantly, and in 7 mg/kg cypermethrin only the weight of
      dorsolateral prostate decreased (P < 0.05). For beta-cypermethrin, any
      antiandrogen effect in in vivo and in vitro experiments was not found in all the
      groups. CONCLUSION: Cypermethrin is a moderate antiandrogen that elicits
      antiandrogenic effects at least partly by antagonizing AR and beta-cypermethrin
      is not an antiandrogen in our experiments.

PMID- 18724889
TI  - [Effect of humidity and temperature on filter and gravimetric measurement of
      ambient particulate matter in a balance room].
AB  - OBJECTIVE: To assess the effects of the alteration of humidity and (or)
      temperature on weight of filters without and with ambient particulate matter in a
      balance room. METHODS: The mass of blank dust sampling filters were weighed under
      (18 +/- 1) degrees C and (28 +/- 1) degrees C respectively, with the humidity
      varying from 35% relative humidity (RH) to 100% RH in a balance room. Then the
      blank filters were divided into two groups and were used to sample total dust and
      respirable dust. After sampling, the loaded filters were re-weighed under above
      conditions and the mass difference before and after the sampling were compared
      and analyzed. RESULTS: The vibration of the average mass of filters varied from
      0.10 to 0.13 mg and from 0.06 to 0.09 mg under the temperatures of (18 +/- 1)
      degrees C and (28 +/- 1) degrees C respectively; When both the temperature and
      humidity changed, it varied from 0.12 to 0.16 mg. The deviation of average mass
      difference ranged from 0.07 to 0.10 mg and from 0.04 to 0.08 mg under the two
      temperatures mentioned above; When both the temperature and humidity changed, it
      varied from 0.09 to 0.14 mg. The average mass of blank filters and loaded filters
      were all positively correlated with the change of humidity (P < 0.01). No effects
      of humidity on the average mass difference of the loaded filters were observed.
      The average mass differences of loaded filters and blank filters under (18 +/- 1)
      degrees C were significantly higher than that under (28 +/- 1) degrees C (P <
      0.01) when humidity was not changed. CONCLUSION: The alteration of humidity and
      (or) temperature in a balance room attributes to the deviation of the measurement
      of the mass of filters and thus affects the gravimetric measurements of ambient
      particulate matter.

PMID- 18724890
TI  - [A test of screening to predict lung cancer among dust-exposed tin miners with
      sputum imaging cytometry].
AB  - OBJECTIVE: To evaluate efficacy of sputum imaging cytometry in early diagnosis on
      lung cancer among tin miners exposed to dust and analyze possible risk factors
      related to lung cancer among tin miners. METHODS: From a cohort of tin miners in
      Guangxi Province, a total of 345 male tin miners higher than 45 years old and
      with high exposure to crystalline silica dust were randomly selected as the
      objects. Imaging cytometry was used to implement the sputum analysis for the
      screening on lung cancer according to the experience diagnostic standard. All
      objects were then followed up to the end of 2006. Clinical diagnosis of lung
      cancer was used as the golden standard to evaluate the efficacy of screening.
      RESULTS: From 1998 to 2006, 11 new cases were diagnosed as clinical lung cancer.
      Except of age and exposure to occupational hazards, smoking status (P = 0.0384)
      and mean smoking dose (P = 0.0078) were significantly associated with lung
      cancer, and the adjusted odds ratio of high level to the low was 18.21 (2.15
      approximately 154.39). The sensitivity, specificity and Youden's index of the
      sputum imaging cytometry for the experience diagnosis were 27.3%, 83.9% and 11.2%
      respectively. According to the ROC curve analysis, area under ROC Curve (AUC) of
      C2.5 (the percentage when the DNA index ranged from 1.25 to 2.50) was 0.647
      (0.525 approximately 0.768), with the optimal operating point (OOP) of 1.70%.
      Sensitivity, specificity, agreement rate, positive predictive value, negative
      predictive value and Youden's index for predicting lung cancers in high-exposure
      tin miners were found to be 72.7%, 62.3%, 62.6%, 6.0%, 98.6% and 35.0%
      respectively. CONCLUSION: Smoking is confirmed as an important risk factor of
      lung cancer in tin miners. The diagnostic efficiency can be improved if the
      diagnostic point of C2.5 is adjusted to 1.70%.

PMID- 18724891
TI  - [Effects of prenatal exposure to low level lead on expression of GAP-43 in
      hippocampus of rat's offspring].
AB  - OBJECTIVE: To observe the effects of prenatal exposure to low level lead on the
      protein and mRNA expression of growth-associated protein (GAP-43) in hippocampus
      of rat's offspring, and to explore the molecular mechanisms of lead on learning
      and memory. METHODS: The pregnant rats were randomizedly divided into 4 groups
      and provided with doubly evaporated water in control group and 125, 250, 500 mg/L
      lead acetate solution via drinking water in treatment groups respectively during
      pregnancy. When the rat's offspring was 1, 21, 60 days old, the lead content in
      hippocampus was measured by hydride generation atomic absorption spectrometry,
      and the GFAP protein and mRNA expression at hippocampal CA1 region were observed
      by immunohistochemistry and in situ hybridization. RESULTS: The content of lead
      in the hippocampus was (1.64 +/- 0.32), (2.33 +/- 0.42) and (3.28 +/- 0.58)
      microg/L, and (0.94 +/- 0.18), (1.27 +/- 0.26) and (1.79 +/- 0.42) microg/L
      respectively in the low, middle and high lead dosage group when the rat's
      offspring was one day and 21 day old. When the rat's offspring was 1, 21 days
      old, the content of lead in hippocampus in treatment groups was significant
      higher than that of control (P < 0.05), the integral optical density of GAP-43
      protein and mRNA expression (except low dosage treatment at 21 d) were
      significantly decreased compared with the control (P < 0.01, P < 0.05), but there
      was no significant difference at 60-day old offsprings for the parameters above.
      CONCLUSION: Exposure to low level lead during pregnancy could inhibit the GAP-43
      protein and mRNA expression in hippocampus of rat's offspring, which may be one
      of the molecular mechanisms of lead on learning and memory.

PMID- 18724893
TI  - [Effect of coking oven emissions on level of serum oxidation-reduction and
      peripheral white blood cellular ras P21 and P53 in coke oven workers].
AB  - OBJECTIVE: To explore the adverse effects of coking oven emissions (COE) on the
      serum oxidation-reduction and relevant genes in the exposed workers. METHODS:
      Fifty-six coke oven workers and forty controls were investigated. Serum
      Malondialdehyde (MDA) levels and the activities of total superoxide dismutases (T
      SOD) were measured by spectrophotometrical method. Immunohistochemical method was
      used to assess the P21 and P53 levels in peripheral white blood cells. RESULTS:
      Compared with controls, the individuals exposed to COE had significantly
      increased levels of serum MDA [(5.30 +/- 2.29) nmol/mL, P < 0.01] and markedly
      decreased levels of T-SOD [(100.04 +/- 10.75) NU/mL]. Additionally, the median
      levels of P53 and P21 were markedly increased in the exposed individuals compared
      with the controls (21.4% and 23.2%, respectively, all P < 0.05). CONCLUSION: The
      findings indicate that occupational exposure to COE causes the rise of serum
      oxidation-reduction MDA and the fall of T-SOD, and increasing expression levels
      of P21 and P53 proteins before the occurrence of apparent clinical symptoms.

PMID- 18724894
TI  - [Effects of melatonin on nerve cell apoptosis and expression of Bcl-2 &
      cytochrome C genes in rat cerebrum with deltamethrin induction].
AB  - OBJECTIVE: To study the effects of melatonin (MT) on nerve cell apoptosis and the
      expression of bcl-2 and cytochrome C genes in rat cerebrum with deltamethrin
      induction. METHODS: 35 male Wistar rats were randomly divided into five groups
      (eight rats per group): olive oil control, deltamethrin-treated (12.5 mg/kg),
      deltamethrin plus melatonin (25.0 mg/kg, 50 mg/kg and 100 mg/kg respectively)
      group. Animal models were established by intraperitoneal injection deltamethrin
      in rats. Nerve cell apoptosis and the protein expression of bcl-2 and cytochrome
      C genes were detected by flow cytometry with PI staining and immunohistochemistry
      respectively. RESULTS: Compared with DM group (20.73 +/- 3.34), the positive
      expression gradation of the bcl-2 protein in nerve cell was increased
      significantly in MT groups (DM + MT(25) was 45.26 +/- 3.84, DM + MT(50) 39.4 +/-
      4.04 and DM + MT(100) 34.4 +/- 4.52) (P < 0.05) but significantly lower than the
      control group (59.33 +/- 4.03). Compared with DM group (34.86 +/- 4.15), the
      cytochrome C protein in nerve cell was decreased significantly in MT groups
      (20.53 +/- 3.17, 28.73 +/- 2.61 and 28.66 +/- 4.82 respectively) (P < 0.05).
      Compared with DM group (23.06 +/- 3.63), the apoptotic rate in nerve cell was
      decreased significantly in MT groups [(15.0 +/- 1.77)%, (14.88 +/- 1.84)% and
      (11.75 +/- 1.93)% respectively] (P < 0.05). CONCLUSION: MT can protect nerve cell
      against deltamethrin induced brain injury by inhibiting nerve cell apoptosis,
      downregulate the protein expression of cytochrome C gene and upregulate the
      protein expression of bcl-2 gene.

PMID- 18724895
TI  - [mRNA expression levels of p53 and DNA damage and repair genes in peripheral
      blood lymphocytes of benzene-exposed workers].
AB  - OBJECTIVE: To investigate the relationship between the mRNA expression levels of
      p53-mediating DNA damage and repair genes in the peripheral blood lymphocytes of
      workers and their exposures to benzene in their working environment. METHODS: The
      mRNA expression levels of p53 and related genes were determined by SYBR Green I
      chimeric fluorescence quantitative real-time RT-PCR analysis in peripheral blood
      lymphocytes of 72 workers, who were classified into group A (46 direct exposure
      to benzene) and group B (26 indirect exposure to benzene) based on their
      positions, and 29 controls. The differences of gene expression levels were
      analyzed by software REST 2005. Meanwhile, the peripheral blood leukocytes,
      hemoglobin and platelet of workers and controls were counted. Benzene content was
      measured in the samples of toluene, used as raw material, and spraying agents and
      benzene, toluene and xylene concentrations in the air of workplaces were
      monitored. RESULTS: There were no significant differences in the mRNA expression
      levels of p53, Ku80, Ape1 and Mdm-2 between group A or group B and control group
      (P > 0.05). The expression up-regulation of p21 mRNA was found, but without
      significant difference (P > 0.05). However, the mRNA expression levels of Rad51,
      Bcl-2, Bax, Xpa and Xpc in group A and Rad51 in group B were downregulated
      significantly (P < 0.05 or P < 0.01). Moreover, both the counts of white blood
      cell, hemoglobin and platelet in group A were (4.93 +/- 1.27) x 10(9)/L, (123.97
      +/- 11.80) g/L and (124.02 +/- 41.22) x 10(9)/L respectively and platelet in
      group B (135.80 +/- 39.44) x 10(9)/L were significantly lower than in control
      group (P < 0.05 or P < 0.01). CONCLUSION: The mRNA expression levels of some p53
      mediating DNA damage and repair genes are downregulated in the workers
      chronically exposed to low benzene concentration. The working environment impacts
      on health of group A workers are greater than the ones of group B.

PMID- 18724897
TI  - [Analysis of pneumoconiosis death cases in Yunnan province between 1950 and
      2000].

PMID- 18724896
TI  - [Effect of dioxin on apoptosis of osteogenic sarcoma cells and regulation on gene
      expression of insulin-like growth factor binding protein 6].
AB  - OBJECTIVE: To investigate the effect of the environmental carcinogenic factor
      TCDD (2, 3, 7, 8-tetrachlorodibenzo-p-dioxin) on cell apoptosis and gene
      regulation of insulin-like growth factor binding protein 6 (IGFBP-6) in
      osteogenic sarcoma (SaOS-2) cells. METHODS: The SaOS-2 cells were cultured with
      TCDD (1 x 10(-9), 1 x 10(-8), 1 x 10(-7) mol/L) for 24 hours. The MTT reduction
      assay and flow cytometry were used to measure the cell proliferation and the cell
      apoptosis in TCDD-treated SaOS-2 cells. The Nitrophenol phosphate salt method was
      used to measure activity of alkaline phosphatase (ALP) in SaOS-2 cells. The IGFBP
      6 mRNA and protein in SaOS-2 cells were detected by reverse transcription
      polymerase chain reaction (RT-PCR) and western blotting analysis. RESULTS: SaOS-2
      cell proliferation was up-regulated with TCDD (1 x 10(-9), 1 x 10(-8), and 1 x
      10(-7) mol/L) about 20%, 47% and 93% (18.4 +/- 4.5, 22.5 +/- 3.6 and 29.4 +/-
      4.2), respectively. The synthesis of ALP was up-regulated about 28%, 95%, and
      142% (1.12 +/- 0.28, 1.58 +/- 0.14 and 1.96 +/- 0.17), respectively (P < 0.05).
      The cell apoptosis was down-regulated in dose-dependent biological manner about
      5%, 26% and 52%, respectively (P < 0.05). The expression of IGFBP-6 mRNA and
      protein was decreased in 1 x 10(-7) mol/L TCDD-treated SaOS-2 cells about 76% and
      72% (P < 0.05). CONCLUSION: TCDD at low concentration may have the negative
      effect on cell apoptosis and down-regulation on gene expression of IGFBP-6 in
      SaOS-2 cells.

PMID- 18724898
TI  - [Investigation on status and need of classification of pneumoconiosis control in
      Tangshan city].

PMID- 18724899
TI  - [Analysis of influence of work experience on training outcome of diagnosis
      criterion of pneumoconiosis].

PMID- 18724900
TI  - [Treatment of acrolein inhalation induced lung injury].

PMID- 18724901
TI  - [Drug resistance of imipenem-resistant Pseudomonas aeruginosa of lower
      respiratory tract in pulmonary heart disease of coal worker's pneumoconiosis].

PMID- 18724902
TI  - [Report on analysis of lung biopsy of pneumoconiosis exposed to antimony
      trioxide].

PMID- 18724903
TI  - [Significance of determination of serum xanthine oxidase and lipid peroxidation
      indexes in acute organophosphorus poisoning].

PMID- 18724904
TI  - [Teratogenic effect of R-d-trans-prallethrin on rats].

PMID- 18724905
TI  - [Change of endothelin-1 and nitrogen monoxide in rats with paraquat poisoning].

PMID- 18724906
TI  - [Therapeutic effects of gamma-hydroxybutyrate and sodium dimercapto sulphonate on
      rats with acute tetramine poisoning].

PMID- 18724907
TI  - [Comparison of chest films of pneumoconiosis taken by high-voltage X-ray and by
      computed X-ray].

PMID- 18724908
TI  - [Comparison of computed X-ray and high-voltage X-ray films in screening and
      survey of pneumoconiosis].

PMID- 18724909
TI  - [Gas chromatography for determination of serum methyl parathion and dimethoate].

PMID- 18724910
TI  - [Advance of research on role of c-Jun in tumorigenesis].

PMID- 18724911
TI  - [Analysis of morbidity of pneumoconiosis in welders of ship building industry].

PMID- 18724912
TI  - [Clinical excellence and information technologies].

PMID- 18724913
TI  - [Knowledge of and opinions on violence against women among health professionals
      in specialized care].
AB  - OBJECTIVE: The aim of this study was to evaluate knowledge of gender violence
      among health workers/medical staff in specialized healthcare and their opinions
      on the subject. A further aim was to identify the organizational barriers
      perceived by these workers and their proposals to enhance the early detection of
      this phenomenon and care of victims. METHOD: We performed an observational, cross
      sectional study based on an anonymous survey of health workers/medical staff
      working in the pediatrics, obstetrics or emergency departments of two hospitals
      in health district 8 of Madrid. RESULTS: Overall, health professionals had
      average knowledge about gender violence. A total of 58.2% believed that physical
      abuse of women was associated with the lower social classes, while 72.8% believed
      that victims were uneducated women, housewives or foreigners; 67.6 % believed
      that aggressors were alcoholic, drug addicted or unemployed men. Almost all
      health professionals (97.7%) considered that gender violence against women was an
      important problem that usually went undetected. However, 66.7% did not include
      this phenomenon in the differential diagnosis of women with physical injuries.
      Notable among the organizational obstacles identified were workload, lack of
      training and information, and the absence of a protocol. CONCLUSIONS: Knowledge
      of gender violence among health professionals was average, with no significant
      differences between hospitals or among the three categories of staff surveyed.
      Stereotyped beliefs were found among health professionals who, nevertheless,
      believed they had an important role in detecting battered women. Reducing the
      organizational barriers detected could improve the care of these patients.

PMID- 18724914
TI  - [Factors predicting new tuberculosis infections and tuberculin conversions in a
      contact tracing system].
AB  - OBJECTIVE: To study new cases of latent tuberculosis (TB) infection, active TB
      and tuberculin conversions detected by means of a system for tracing the contacts
      of TB patients and to analyze the factors that predict the appearance of new
      cases. METHOD: We performed a longitudinal, prospective study of all contacts of
      patients with active TB in the health district of Vigo, Pontevedra, in 2005 and
      2006. The total rate of positive tuberculin test results and the percentage of
      tuberculin conversions at the end of the study were analyzed. The predictive
      factors for positive results were identified by a multivariate analysis. RESULTS:
      A total of 742 contacts of patients with TB were studied. The mean age of
      contacts was 35 years (SD=19.1) and 406 (54.7%) were women. Most (91.8%) were
      contacts of pulmonary TB patients, 70.4% were contacts of bacilliferous patients
      and 40.2% were highly exposed. The study was completed with 540 (72.8%) cases,
      280 (51.9%) of which were infected or diseased. Of the 297 contacts who completed
      the study 12 weeks later, 37 (12.5%) showed tuberculin conversion. The factors
      independently associated with a positive tuberculin test result were male sex,
      age >or= 30 years old, and degree of contact (high exposure in contacts and
      positive sputum smear in the index case); the two latter factors were predictive
      for tuberculin conversion. CONCLUSION: Contact tracing of TB patients was an
      effective strategy in our area. The factors most closely related to positive
      tuberculin test results, particularly to conversion, were positive direct
      microscopy of sputum for the index case and high exposure. Strategies to improve
      adherence to this kind of study should be sought.

PMID- 18724915
TI  - [Hospital nurses' knowledge of the patient care plan for immediate life
      threatening situations].
AB  - OBJECTIVE: To evaluate knowledge of nurses in adult hospital units in Txagorritxu
      Hospital (Vitoria) on care plans for immediate life-threatening (ILT) situations
      and to determine their self-evaluation of knowledge of cardiopulmonary
      resuscitation and the main sociodemographic characteristics that could influence
      the need for better training in this field. METHOD: We performed a cross
      sectional, analytical, observational study through a survey of 207 nurses in
      adult hospital units. Data were collected using a self-administered 20-item
      questionnaire. Five of these items measured knowledge of the care plan for ILT
      situations. RESULTS: The response rate was 74.39%. Of the five questions
      measuring knowledge, 32.4% of the nurses answered four or more questions
      correctly. Of the total, 38.3% knew when to activate the ILT plan; 12.99% did not
      know how to remove or lower the bed head when the patient was experiencing an ILT
      situation, and 24.03% did so with difficulty. No significant differences were
      found in nurses' experience, age, or the percentage of correct responses.
      CONCLUSIONS: Training courses should be organized to enable nurses to act in an
      ILT situation, including when to activate the care plan, how to perform the
      measures, and how to handle the center's materials/equipment.

PMID- 18724916
TI  - [Satisfaction and personal experience of subcutaneous vascular access in 50
      oncological patients].
AB  - OBJECTIVE: To describe the personal experience of patients with central venous
      access (CVA) devices: satisfaction, fears and concerns, the influence of the
      devices on their daily lives, and the healthcare received. METHOD: We performed a
      descriptive, longitudinal, prospective study in a sample of 50 patients with CVA
      devices withdrawn in the Angiography Unit of the Hospital de Navarra between
      August 1, 2006 and March 1, 2007. A 26-item questionnaire (Likert-like 5-point
      scale) was used. The statistical analysis was performed using the SPSS 13.0
      package. RESULTS: Fifty patients were interviewed, 18 men and 32 women, with a
      mean age of 52.54 years. The most frequent disease was colon cancer. The mean
      catheter dwell time was 369.52 days and the most frequent complication was
      hematoma. CONCLUSIONS: The patients were satisfied with the device and would be
      willing to have another inserted, if necessary. Patients tended not to worry
      about complications and perceived the catheter as a foreign body. Arm movement
      was hardly restricted. Nursing care of the device was deficient in some patients.

PMID- 18724917
TI  - [Factors associated with long-term retention among nurses in an intensive care
      unit].
AB  - OBJECTIVE: To identify which factors motivate nurses with more than 10 years'
      experience in the ICU of the Hospital General Universitario de Alicante to stay
      in the unit and to analyze the reasons for leaving in nurses who left this ICU
      after more than 10 years. METHOD: We performed a descriptive, observational,
      cross-sectional study. Thirty-two nurses who had worked in the ICU for more than
      10 years completed a written questionnaire. In the 18 nurses that had left the
      ICU, the reasons for leaving were determined. The results are expressed in
      relative frequencies and percentages. RESULTS: Twenty nurses (62%) continued to
      work in the ICU because they liked the service and five (16%) because they had
      not been able to work in a position they liked more. Of the nurses who had left
      the ICU after 10 or more years, 67% had done so to work on a fixed shift.
      CONCLUSIONS: Most of the nurses who had worked for more than 10 years in the ICU
      stayed because they liked the service, while most of those who left did so to
      work fixed shifts.

PMID- 18724918
TI  - [Where to begin?: the qualitative research question].
AB  - A qualitative research question reflects the researcher's paradigm and should be
      consistent with the proposed research method. A research question implies
      engaging in a process that defines the research area, subject, question, and
      place of the study. Because this process is interactive and changes during the
      course of the investigation, the beginnings are necessarily provisional. The
      qualitative research question is constructed, is central to the research process,
      and differs from what is commonly expected of a research question. Once
      formulated, the pertinence of the research question must be argued. Justifying a
      study does not imply an exhaustive literature review, but rather a selective one,
      by selecting the data that support the need for the study and the relevance of
      the research question. In practice, constructing a research question involves two
      phases: a first phase of intuitive reasoning and a second phase of theoretical
      and practical reasoning. A qualitative study can be prompted by distinct factors,
      common ones being personal experience, conversations with colleagues, lines of
      research, and the library.

PMID- 18724919
TI  - [Insertion and maintenance of peripheral venous catheters in neonates].
AB  - Insertion of peripheral venous catheters in premature and term newborns is a
      common practice in neonatology units and neonatal intensive care units. Nurses
      are responsible for the insertion and maintenance of peripheral venous catheters
      and for the prevention of complications. Although this technique is routine, a
      series of recommendations, supported by evidence-based practice, should be bourne
      in mind when inserting these catheters. Following these recommendations
      guarantees successful insertion, and the absence of risks and complications. To
      achieve this aim, the following steps should be carried out: preparing the
      material, selecting the vein, selecting the catheter, cleaning and disinfecting
      the area, inserting the catheter, fixing the catheter, and restoring intravenous
      therapy. In addition, attention must be paid to potential risks in order to
      resolve them as quickly as possible, thereby avoiding complications.

PMID- 18724920
TI  - [Case report: a gastrectomized patient under treatment with chemotherapy and
      radiotherapy].
AB  - The adjuvant treatment of gastric cancer includes radiotherapy and chemotherapy.
      The patient underwent gastrectomy on November 10, 2006 and began adjuvant
      chemotherapy (McDonald scheme) on january 2, 2007, finishing on june 1, 2007.
      Radiotherapy was started on February 6, 2007 and finished on March 16, 2007. The
      care plan presented was designed following the Virginia Henderson model and is
      routinely used at the Reina Sofia Hospital. This care plan follows the NANDA, NOC
      and NIC taxonomies and is based on the following nursing diagnoses: risk of
      infection, fear, and disposition to improve knowledge. During the clinical
      course, two new nursing diagnoses were identified: deterioration of oral mucosa
      and skin integrity.

PMID- 18724923
TI  - [The electrocardiogram as a nursing technique: quality of the
      electrocardiographic trace].

PMID- 18724924
TI  - [The Guthrie test: another perspective of the heel prick test in the newborn].

PMID- 18724925
TI  - Toxicity testing moves from the legislature to the petri dish-and back.
AB  - With the growing cost of using animals to test the safety of new chemicals and an
      increasing backlog of chemicals awaiting testing, the quest for cell-based in
      vitro alternatives for toxicity testing is gaining momentum.

PMID- 18724926
TI  - Proteomics joins the search for microRNA targets.
AB  - Two recent studies published in Nature (Baek et al. 2008; Selbach et al., 2008)
      analyze changes in the proteome in response to individual microRNAs (miRNAs).
      This approach is a powerful means to identify miRNA targets and to quantify the
      contribution of translational repression to posttranscriptional gene silencing by
      miRNAs.

PMID- 18724927
TI  - Senescence: not just for tumor suppression.
AB  - Cellular senescence provides an intrinsic barrier to tumor development by
      preventing the proliferation of cells that are at risk for malignant
      transformation. In this issue, Krizhanovsky et al. (2008) report that senescence
      is an important player not only in tumor suppression but also in the response of
      liver tissue to injury.

PMID- 18724928
TI  - Gle1 does double duty.
AB  - During nuclear export, Gle1 (the nuclear-pore-associated mRNA export factor)
      activates the DEAD-box protein Dbp5 to remodel exported mRNA-protein complexes on
      the cytoplasmic face of the nuclear pore complex. In this issue, Bolger et al.
      (2008) now report additional roles for Gle1 in translation initiation and
      termination.

PMID- 18724929
TI  - Silencing HIV-1 In Vivo.
AB  - RNA interference holds great promise for antiviral therapy, but delivering
      effective quantities of small interfering RNAs (siRNAs) into the right target
      cells in vivo represents a major challenge. Kumar et al. (2008) now report a
      technique to target siRNAs specifically to T cells to suppress viral infection in
      a humanized mouse model of HIV/AIDS.

PMID- 18724930
TI  - Linking retroelements to autoimmunity.
AB  - In this issue, Stetson et al. (2008) report a mechanism by which host cells avert
      an autoimmune response to self-nucleic acids. They show that the nuclease Trex1
      prevents the accumulation of DNA derived from endogenous retroelements that, if
      left unchecked, trigger elevated production of type I interferons leading to
      autoimmunity.

PMID- 18724931
TI  - A tale of too many centrosomes.
AB  - Having the correct number of centrosomes is crucial for proper chromosome
      segregation during cell division and for the prevention of aneuploidy, a hallmark
      of many cancer cells. Several recent studies (Basto et al., 2008; Kwon et al.,
      2008; Yang et al., 2008) reveal the importance of mechanisms that protect against
      the consequences of harboring too many centrosomes.

PMID- 18724932
TI  - Trex1 prevents cell-intrinsic initiation of autoimmunity.
AB  - Detection of nucleic acids and induction of type I interferons (IFNs) are
      principal elements of antiviral defense but can cause autoimmunity if
      misregulated. Cytosolic DNA detection activates a potent, cell-intrinsic
      antiviral response through a poorly defined pathway. In a screen for proteins
      relevant to this IFN-stimulatory DNA (ISD) response, we identify 3' repair
      exonuclease 1 (Trex1). Mutations in the human trex1 gene cause Aicardi-Goutieres
      syndrome (AGS) and chilblain lupus, but the molecular basis of these diseases is
      unknown. We define Trex1 as an essential negative regulator of the ISD response
      and delineate the genetic pathway linking Trex1 deficiency to lethal
      autoimmunity. We show that single-stranded DNA derived from endogenous
      retroelements accumulates in Trex1-deficient cells, and that Trex1 can metabolize
      reverse-transcribed DNA. These findings reveal a cell-intrinsic mechanism for
      initiation of autoimmunity, implicate the ISD pathway as the cause of AGS, and
      suggest an unanticipated contribution of endogenous retroelements to
      autoimmunity.

PMID- 18724934
TI  - The regulation and evolution of a genetic switch controlling sexually dimorphic
      traits in Drosophila.
AB  - Sexually dimorphic traits play key roles in animal evolution and behavior. Little
      is known, however, about the mechanisms governing their development and
      evolution. One recently evolved dimorphic trait is the male-specific abdominal
      pigmentation of Drosophila melanogaster, which is repressed in females by the
      Bric-a-brac (Bab) proteins. To understand the regulation and origin of this
      trait, we have identified and traced the evolution of the genetic switch
      controlling dimorphic bab expression. We show that the HOX protein Abdominal-B
      (ABD-B) and the sex-specific isoforms of Doublesex (DSX) directly regulate a bab
      cis-regulatory element (CRE). In females, ABD-B and DSX(F) activate bab
      expression whereas in males DSX(M) directly represses bab, which allows for
      pigmentation. A new domain of dimorphic bab expression evolved through multiple
      fine-scale changes within this CRE, whose ancestral role was to regulate other
      dimorphic features. These findings reveal how new dimorphic characters can emerge
      from genetic networks regulating pre-existing dimorphic traits.

PMID- 18724933
TI  - A sequence motif within chromatin entry sites directs MSL establishment on the
      Drosophila X chromosome.
AB  - The Drosophila MSL complex associates with active genes specifically on the male
      X chromosome to acetylate histone H4 at lysine 16 and increase expression
      approximately 2-fold. To date, no DNA sequence has been discovered to explain the
      specificity of MSL binding. We hypothesized that sequence-specific targeting
      occurs at "chromatin entry sites," but the majority of sites are sequence
      independent. Here we characterize 150 potential entry sites by ChIP-chip and ChIP
      seq and discover a GA-rich MSL recognition element (MRE). The motif is only
      slightly enriched on the X chromosome ( approximately 2-fold), but this is
      doubled when considering its preferential location within or 3' to active genes
      (>4-fold enrichment). When inserted on an autosome, a newly identified site can
      direct local MSL spreading to flanking active genes. These results provide strong
      evidence for both sequence-dependent and -independent steps in MSL targeting of
      dosage compensation to the male X chromosome.

PMID- 18724935
TI  - The mRNA export factor Gle1 and inositol hexakisphosphate regulate distinct
      stages of translation.
AB  - Gene expression requires proper messenger RNA (mRNA) export and translation.
      However, the functional links between these consecutive steps have not been fully
      defined. Gle1 is an essential, conserved mRNA export factor whose export function
      is dependent on the small molecule inositol hexakisphosphate (IP(6)). Here, we
      show that both Gle1 and IP(6) are required for efficient translation termination
      in Saccharomyces cerevisiae and that Gle1 interacts with termination factors. In
      addition, Gle1 has a conserved physical association with the initiation factor
      eIF3, and gle1 mutants display genetic interactions with the eIF3 mutant nip1-1.
      Strikingly, gle1 mutants have defects in initiation, whereas strains lacking
      IP(6) do not. We propose that Gle1 functions together with IP(6) and the DEAD-box
      protein Dbp5 to regulate termination. However, Gle1 also independently mediates
      initiation. Thus, Gle1 is uniquely positioned to coordinate the mRNA export and
      translation mechanisms. These results directly impact models for perturbation of
      Gle1 function in pathophysiology.

PMID- 18724936
TI  - The GET complex mediates insertion of tail-anchored proteins into the ER
      membrane.
AB  - Tail-anchored (TA) proteins, defined by the presence of a single C-terminal
      transmembrane domain (TMD), play critical roles throughout the secretory pathway
      and in mitochondria, yet the machinery responsible for their proper membrane
      insertion remains poorly characterized. Here we show that Get3, the yeast homolog
      of the TA-interacting factor Asna1/Trc40, specifically recognizes TMDs of TA
      proteins destined for the secretory pathway. Get3 recognition represents a key
      decision step, whose loss can lead to misinsertion of TA proteins into
      mitochondria. Get3-TA protein complexes are recruited for endoplasmic reticulum
      (ER) membrane insertion by the Get1/Get2 receptor. In vivo, the absence of
      Get1/Get2 leads to cytosolic aggregation of Get3-TA complexes and broad defects
      in TA protein biogenesis. In vitro reconstitution demonstrates that the Get
      proteins directly mediate insertion of newly synthesized TA proteins into ER
      membranes. Thus, the GET complex represents a critical mechanism for ensuring
      efficient and accurate targeting of TA proteins.

PMID- 18724937
TI  - Opposing Wnt pathways orient cell polarity during organogenesis.
AB  - The orientation of asymmetric cell division contributes to the organization of
      cells within a tissue or organ. For example, mirror-image symmetry of the C.
      elegans vulva is achieved by the opposite division orientation of the vulval
      precursor cells (VPCs) flanking the axis of symmetry. We characterized the
      molecular mechanisms contributing to this division pattern. Wnts MOM-2 and LIN-44
      are expressed at the axis of symmetry and orient the VPCs toward the center.
      These Wnts act via Fz/LIN-17 and Ryk/LIN-18, which control beta-catenin
      localization and activate gene transcription. In addition, VPCs on both sides of
      the axis of symmetry possess a uniform underlying "ground" polarity, established
      by the instructive activity of Wnt/EGL-20. EGL-20 establishes ground polarity via
      a novel type of signaling involving the Ror receptor tyrosine kinase CAM-1 and
      the planar cell polarity component Van Gogh/VANG-1. Thus, tissue polarity is
      determined by the integration of multiple Wnt pathways.

PMID- 18724938
TI  - Senescence of activated stellate cells limits liver fibrosis.
AB  - Cellular senescence acts as a potent mechanism of tumor suppression; however, its
      functional contribution to noncancer pathologies has not been examined. Here we
      show that senescent cells accumulate in murine livers treated to produce
      fibrosis, a precursor pathology to cirrhosis. The senescent cells are derived
      primarily from activated hepatic stellate cells, which initially proliferate in
      response to liver damage and produce the extracellular matrix deposited in the
      fibrotic scar. In mice lacking key senescence regulators, stellate cells continue
      to proliferate, leading to excessive liver fibrosis. Furthermore, senescent
      activated stellate cells exhibit gene expression profile consistent with cell
      cycle exit, reduced secretion of extracellular matrix components, enhanced
      secretion of extracellular matrix-degrading enzymes, and enhanced immune
      surveillance. Accordingly natural killer cells preferentially kill senescent
      activated stellate cells in vitro and in vivo, thereby facilitating the
      resolution of fibrosis. Therefore, the senescence program limits the fibrogenic
      response to acute tissue damage.

PMID- 18724939
TI  - Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies.
AB  - Posttranslational modification of proteins with polyubiquitin occurs in diverse
      signaling pathways and is tightly regulated to ensure cellular homeostasis.
      Studies employing ubiquitin mutants suggest that the fate of polyubiquitinated
      proteins is determined by which lysine within ubiquitin is linked to the C
      terminus of an adjacent ubiquitin. We have developed linkage-specific antibodies
      that recognize polyubiquitin chains joined through lysine 63 (K63) or 48 (K48). A
      cocrystal structure of an anti-K63 linkage Fab bound to K63-linked diubiquitin
      provides insight into the molecular basis for specificity. We use these
      antibodies to demonstrate that RIP1, which is essential for tumor necrosis factor
      induced NF-kappaB activation, and IRAK1, which participates in signaling by
      interleukin-1beta and Toll-like receptors, both undergo polyubiquitin editing in
      stimulated cells. Both kinase adaptors initially acquire K63-linked
      polyubiquitin, while at later times K48-linked polyubiquitin targets them for
      proteasomal degradation. Polyubiquitin editing may therefore be a general
      mechanism for attenuating innate immune signaling.

PMID- 18724941
TI  - SnapShot: Nonmotor proteins in spindle assembly.

PMID- 18724942
TI  - A little hope amidst war.

PMID- 18724940
TI  - Global mapping of the topography and magnitude of proteolytic events in
      apoptosis.
AB  - Proteolysis is a key regulatory process that promotes the (in)activation,
      translocation, and/or degradation of proteins. As such, there is considerable
      interest in methods to comprehensively characterize proteolytic pathways in
      biological systems. Here, we describe a robust and versatile proteomic platform
      that enables direct visualization of the topography and magnitude of proteolytic
      events on a global scale. We use this method to generate a proteome-wide map of
      proteolytic events induced by the intrinsic apoptotic pathway. This profile
      contained 91 characterized caspase substrates as well as 170 additional proteins
      not previously known to be cleaved during apoptosis. Surprisingly, the vast
      majority of proteolyzed proteins, regardless of the extent of cleavage, yielded
      persistent fragments that correspond to discrete protein domains, suggesting that
      the generation of active effector proteins may be a principal function of
      apoptotic proteolytic cascades.

PMID- 18724943
TI  - Methadone-associated sudden cardiac death?

PMID- 18724945
TI  - Blood pressure reduction in the elderly: how low is too low?

PMID- 18724946
TI  - Statins and cancer risk: decrease or increase?

PMID- 18724948
TI  - Systolic hypertension is also the neglected stepsister of aortic stenosis.

PMID- 18724950
TI  - Troponins: not always a myocardial infarction.

PMID- 18724951
TI  - Crucial role of laboratory tests in modern medicine.

PMID- 18724953
TI  - A rare nasal tip skin metastasis of a basaloid squamous cell carcinoma of the
      larynx.

PMID- 18724954
TI  - Adult-onset homocystinuria arteriopathy mimics fibromuscular dysplasia.

PMID- 18724955
TI  - Acute phase reaction with intravenous ibandronate.

PMID- 18724956
TI  - Middle-age initiation of alcohol consumption unlikely to cause addiction.

PMID- 18724957
TI  - How green is the green journal?

PMID- 18724958
TI  - When guidelines need guidance...

PMID- 18724959
TI  - Treatment of osteoporosis: all the questions we still cannot answer.
AB  - Many questions remain with regard to the treatment of osteoporosis. The increase
      in bone mineral density due to bisphosphonates accounts for only a quarter of
      their antifracture action. The studies of bone mineral density equivalences that
      have validated certain modes of administration are therefore not relevant. No
      comparative study on the same patient cohort has been carried out, and the
      inclusion criteria of the pilot studies on the drugs currently available are all
      different. This makes any comparison impossible, and thus, the choice of
      treatment is subjective. Certain combinations (antiresorptive drugs and anabolic
      agents) are logical, but no major study is available to validate them. Drugs with
      a long latency period could interfere with later treatments or allow therapeutic
      windows, but the data in the literature in support of these hypotheses are
      scarce. The osteoporotic patient will require treatment for 10 to 30 years,
      depending on the age at diagnosis, but the available data on the efficacy and
      nontoxicity of the drugs are based on studies of a duration of only 3 or 5 years.

PMID- 18724960
TI  - Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and
      therapeutic options.
AB  - Diabetic cardiomyopathy is the presence of myocardial dysfunction in the absence
      of coronary artery disease and hypertension. Hyperglycemia seems to be central to
      the pathogenesis of diabetic cardiomyopathy and to trigger a series of
      maladaptive stimuli that result in myocardial fibrosis and collagen deposition.
      These processes are thought to be responsible for altered myocardial relaxation
      characteristics and manifest as diastolic dysfunction on imaging. Sophisticated
      imaging technologies also have permitted the detection of subtle systolic
      dysfunction in the diabetic myocardium. In the early stages, these changes appear
      reversible with tight metabolic control, but as the pathologic processes become
      organized, the changes are irreversible and contribute to an excess risk of heart
      failure among diabetic patients independently of common comorbidities, such as
      coronary artery disease and hypertension. Therapeutic agents specifically
      targeting processes that lead to these pathophysiologic changes are in the early
      stages of development. Although glycemic control and early administration of
      neurohormonal antagonists remain the cornerstones of therapeutic approaches,
      newer treatment targets are currently being explored.

PMID- 18724962
TI  - Frostbite.

PMID- 18724963
TI  - From gut to bone.

PMID- 18724961
TI  - Discerning patterns of human immunodeficiency virus risk in healthy young adults.
AB  - Previous research has questioned the effectiveness of existing methods to
      identify individuals at high risk for contracting and transmitting human
      immunodeficiency virus and other sexually transmitted diseases. Thus, new
      approaches are needed to provide these individuals with risk-reduction
      strategies. We review our research on young adults' sexual decision making by
      using theories and methods from social and cognitive sciences. Four patterns of
      condom use and associated levels of risks and beliefs were identified. These
      patterns suggest value in targeting intervention strategies to individuals at
      different levels of risk. The findings also imply that the monogamous population
      may be at higher risk for infection than they realize. Primary-care physicians
      are the first line of contact for many individuals in the health care system and
      may be in the best position to screen for at-risk individuals. Given the time
      demands and other barriers, easy-to-use, evidence-based guidelines for such
      screening are needed. We propose such guidelines for primary-care physicians to
      use in identifying an individual's risk, from which custom-tailored intervention
      strategies can be developed.

PMID- 18724964
TI  - Unintended consequences. Vena cava filter migration.

PMID- 18724965
TI  - Inka dinka don't. Herpes zoster.

PMID- 18724966
TI  - Three's company: an unusual clue.

PMID- 18724967
TI  - A ticking time bomb--high pressure pulmonary artery aneurysm.

PMID- 18724968
TI  - Serum total bilirubin level, prevalent stroke, and stroke outcomes: NHANES 1999
      2004.
AB  - BACKGROUND: Bilirubin inhibits experimental atherosclerosis, is inversely
      associated with carotid plaque burden, and confers neuroprotection in
      experimental stroke. Clinical data addressing the association of bilirubin with
      stroke are not available. We hypothesized that higher bilirubin levels would be
      associated with reduced stroke prevalence and improved stroke outcomes. METHODS:
      We used the National Health and Nutrition Examination Survey 1999 to 2004, a
      nationally representative cross-sectional examination of the United States
      civilian population, to examine the association of bilirubin with stroke. Of
      13,214 adult participants with data on stroke history, serum total bilirubin
      level, and stroke risk factors, 453 reported a history of stroke. Of these, 138
      participants reported an adverse stroke outcome, defined as a long-term health
      problem or disability due to stroke. We performed multivariable logistic
      regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) with
      adjustment for demographic characteristics and stroke risk factors. RESULTS:
      After multivariable adjustment, a 1.71 micromol/L (0.1 mg/dL) increment in
      bilirubin level was associated with a 9% reduced odds of stroke (OR 0.91; 95% CI,
      0.86-0.96) among all participants and with a 10% reduced odds of an adverse
      stroke outcome (OR 0.90; 95% CI, 0.80-1.00) among participants with a history of
      stroke. CONCLUSIONS: These results suggest that a higher serum total bilirubin
      level is associated with reduced stroke prevalence and improved stroke outcomes.
      Our findings support the hypothesis that bilirubin may protect from stroke events
      and from neurologic damage in stroke.

PMID- 18724970
TI  - Early sustained ventricular arrhythmias complicating acute myocardial infarction.
AB  - OBJECTIVE: Sustained ventricular arrhythmias complicate 2% to 20% of acute
      myocardial infarctions (MIs) and are associated with increased in-hospital
      mortality. However, it remains unclear whether successful mechanical
      revascularization improves outcomes in these patients. The objective of this
      analysis was to identify predictors of sustained ventricular arrhythmias after
      acute MI and to determine the influence of successful revascularization on in
      hospital mortality. METHODS: We conducted a retrospective cohort study of all
      patients who underwent percutaneous coronary intervention for acute MI in New
      York State between 1997 and 1999. RESULTS: Of the 9015 patients who underwent
      percutaneous coronary intervention for acute MI, 472 (5.2%) developed sustained
      ventricular tachycardia (VT) or ventricular fibrillation (VF) before
      revascularization. After multivariable adjustment, independent predictors of
      sustained VT/VF included cardiogenic shock (odds ratio [OR], 4.10; 95% confidence
      interval [CI], 3.20-5.58; P <.001), heart failure (OR, 2.86; 95% CI, 2.24-3.67: P
      <.001), chronic kidney disease (OR, 2.58; 95% CI, 1.27-5.23; P=.009), and
      presentation within 6 hours of symptom onset (OR, 1.46; 95% CI, 1.18-1.81;
      P=.001). Patients with sustained VT/VF had greater in-hospital mortality (16.3%
      vs 3.7%, P <.001). Although successful percutaneous coronary intervention was
      associated with decreased in-hospital mortality in patients with VT/VF (P <.001),
      patients with sustained VT/VF and successful revascularization experienced
      increased mortality compared with patients without sustained ventricular
      arrhythmias (P <.001). CONCLUSION: Among patients undergoing percutaneous
      coronary intervention for acute MI, sustained VT/VF remains a significant
      complication associated with a 4-fold increased risk of in-hospital mortality.
      Early mortality is reduced after successful percutaneous coronary intervention,
      but remains elevated in this high-risk group.

PMID- 18724969
TI  - COPD as a systemic disease: impact on physical functional limitations.
AB  - PURPOSE: Although chronic obstructive pulmonary disease (COPD) has a major impact
      on physical health, the specific impact of COPD on physical functional
      limitations has not been characterized clearly. We aimed to elucidate the
      physical functional limitations that are directly attributable to COPD compared
      to a matched referent group without the condition. METHODS: We used the Function,
      Living, Outcomes, and Work (FLOW) cohort study of adults with COPD (n=1202) and
      referent subjects matched by age, sex, and race (n=302) to study the impact of
      COPD on the risk of a broad array of functional limitations using validated
      measures: lower extremity function (Short Physical Performance Battery [SPPB]),
      submaximal exercise performance (Six Minute Walk Test [SMWT]), standing balance
      (Functional Reach Test), skeletal muscle strength (manual muscle testing with
      dynamometry), and self-reported functional limitation (standardized item
      battery). Multivariate analysis was used to control for confounding by age, sex,
      race, height, educational attainment, and cigarette smoking. RESULTS: COPD was
      associated with poorer lower extremity function (mean SPPB score decrement for
      COPD vs referent -1.0 points; 95% CI, -1.25 to -0.73 pts) and less distance
      walked during the SMWT (-334 feet; 95% CI, -384 to -282 ft). COPD also was
      associated with weaker muscle strength in every muscle group tested, including
      both the upper and lower extremities (P<.0001 in all cases) and with a greater
      risk of self-reported functional limitation (OR 6.4; 95% CI, 3.7 to 10.9).
      CONCLUSIONS: A broad array of physical functional limitations were specifically
      attributable to COPD. COPD affects a multitude of body systems remote from the
      lung.

PMID- 18724971
TI  - Excess heparin dosing among fibrinolytic-treated patients with ST-segment
      elevation myocardial infarction.
AB  - BACKGROUND: Although the use of heparin with fibrinolytics is associated with
      more rapid ST-segment resolution and increased infarct-related artery patency
      among patients with ST-segment elevation myocardial infarction (STEMI), its
      associated increase in bleeding risk is well documented and might be augmented by
      excess heparin dosing. METHODS: We sought to characterize the incidence and
      associated bleeding risk of excess heparin dosing among patients with STEMI
      treated with fibrinolysis who were enrolled in the Can Rapid Risk Stratification
      of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation
      of the American College of Cardiology/American Heart Association Guidelines
      initiative. Excess dosing was defined as a bolus more than 60 U/kg or an infusion
      more than 12 U/kg/h per American College of Cardiology/American Heart Association
      guidelines and was further stratified into major and mild excess (major defined
      as a bolus>70 U/kg or infusion >15 U/kg/h). RESULTS: Among 964 fibrinolytic
      treated patients with STEMI, 758 (79%) received adjunctive unfractionated heparin
      therapy. Of these, 368 patients (49%) received excess dosing of unfractionated
      heparin and 137 patients (18%) received major excess heparin dosing. Factors
      significantly associated with excess dosing included low body weight and female
      sex. Patients who received major excess dosing had higher unadjusted rates of
      major bleeding (19.2% vs 12.4%, P=.004) and transfusion (13.5% vs 4.7%, P=.0002)
      than patients without excess dosing. After adjustment, a trend persisted for the
      association with higher transfusion risk (odds ratio 1.39 [0.61-3.14]).
      CONCLUSION: Approximately half of fibrinolytic-treated patients with STEMI in
      contemporary practice received an excess dose of unfractionated heparin. Careful
      attention to dosing is needed to limit the compounded bleeding risk when heparin
      is added to fibrinolytic therapy.

PMID- 18724973
TI  - The eldest of older adults living with HIV: response and adherence to highly
      active antiretroviral therapy.
AB  - OBJECTIVE: The study objective was to analyze the characteristics and the
      response to therapy in the eldest of the older adults living with human
      immunodeficiency virus. METHODS: The study included a cohort of patients with
      human immunodeficiency virus aged 55 years or more on initiating highly active
      antiretroviral therapy (HAART). Immunologic and virologic response, morbidity,
      and mortality were assessed. Patients were categorized as aged less than 65 years
      and 65 years or more. RESULTS: A total of 112 patients were included (82 patients
      aged<65 years and 30 patients aged> or =65 years). There were no differences
      between the age groups in baseline characteristics, survival, and virologic
      response. There was a trend toward better adherence and a lower CD4+ cell
      increase after HAART in the older group. CONCLUSION: A relationship was found
      between lower CD4+ cell increase after HAART and advanced age. We found the best
      adherence to treatment in the eldest of the older adults, and this has been shown
      to be the only protective independent factor related to virologic failure.

PMID- 18724972
TI  - Sex differences in environmental and genetic factors for hypertension.
AB  - BACKGROUND: Sex differences are observed in many aspects of mammalian
      cardiovascular function and pathology. Hypertension is more common in men than in
      women of the same age. Although the effects of gonadal hormones on blood pressure
      are considered contributing factors, the reasons for sex differences in
      hypertension are still not fully understood. The present study was undertaken to
      compare the differences in several environmental and genetic factors between men
      and women in the Hei Yi Zhuang, an isolated subgroup of the Zhuang minority in
      China. METHODS: Information on demography, diet, and lifestyle was collected in
      835 women and 834 men aged 15 to 84 years. Genotyping of angiotensin-converting
      enzyme, adrenergic receptor beta(3), aldehyde dehydrogenase 2, calpastatin,
      connexin 37, hepatic lipase, lipoprotein lipase, peroxisome proliferator
      activated receptor gamma, thyrotropin-releasing hormone receptor, and von
      Willebrand factor also was performed in these subjects. RESULTS: The levels of
      systolic and diastolic blood pressure, and the prevalence, awareness, and
      treatment of hypertension were lower in women than in men (P < .05). Hypertension
      was positively associated with age, physical activity, alcohol consumption, body
      mass index, waist circumference, hyperlipidemia, total energy, total fat, sodium
      intake, and sodium/potassium ratio, and negatively associated with education
      level, total dietary fiber, potassium intake, angiotensin-converting enzyme,
      aldehyde dehydrogenase 2, and hepatic lipase genotypes in men (P < .05).
      Hypertension was positively associated with age, hyperlipidemia, total energy,
      total fat, sodium intake, sodium/potassium ratio, calpastatin, and von Willebrand
      factor genotypes, and negatively associated with education level, total dietary
      fiber, potassium, calcium intake, lipoprotein lipase, and thyrotropin-releasing
      hormone receptor genotypes in women (P < .05). CONCLUSION: Sex differences in the
      prevalence of hypertension in the Hei Yi Zhuang population may be mainly
      attributed to the differences in dietary habits, lifestyle choices, sodium and
      potassium intakes, physical activity level, and some genetic polymorphisms.

PMID- 18724974
TI  - Physicians, their appearance, and the white coat.

PMID- 18724975
TI  - Mind over body: the diving bell and the butterfly.

PMID- 18724976
TI  - How to ensure our readers' trust: the proper attribution of authors and
      contributors.

PMID- 18724977
TI  - Calcification of hydrophilic acrylic intraocular lenses.

PMID- 18724978
TI  - Clues as to the pathophysiology of retinal hemorrhages in Shaken Baby syndrome
      determined with optical coherence tomography.

PMID- 18724979
TI  - Distinguishing between infectious and noninfectious endophthalmitis after
      intravitreal triamcinolone injection.

PMID- 18724980
TI  - The pathogenesis of age-related macular degeneration.

PMID- 18724981
TI  - Dome-shaped macula in eyes with myopic posterior staphyloma.

PMID- 18724984
TI  - Pars planitis: a 20-year study of incidence, clinical features, and outcomes.

PMID- 18724985
TI  - Simultaneous determination of major to ultratrace elements in geological samples
      by fusion-dissolution and inductively coupled plasma mass spectrometry
      techniques.
AB  - A method has been developed for the simultaneous quantification of major to
      ultratrace elements in geological samples using quadrupole ICP-MS techniques. The
      sample preparation involves fusion with LiBO2 and dilution in HNO3-HF which
      allows complete decomposition of refractory minerals and quantification of the
      elements of interest. The effects of high Total Dissolved Solids (TDS) and Li in
      the solution are minimized using a matrix-tolerant interface and conditioning the
      instrument with LiBO2 solution. The signal drift is moreover controlled using
      conventional internal standards and specific Drift Correction Standards (DCS). A
      key issue of the technique is the external calibration using selected Certified
      Reference Materials (CRM). Depending on the sample type and analytes of interest
      three optimized programmable modes are used sequentially: Standard, Collision
      Cell (CCT) and Kinetic Energy Discrimination (KED) mode. The method allows to
      quantify more than 40 elements in concentrations from tens-of-percent to <0.1 ppm
      levels during a single experiment. The method has been validated through the
      analysis of different CRMs with recovery factors of ca. 100% and typical 2sigma
      errors of <10%.

PMID- 18724986
TI  - On-line redox speciation analysis of antimony using l-proline immobilized on
      controlled pore glass and hydride generation inductively coupled plasma optical
      emission spectrometry for detection.
AB  - L-proline was immobilized on controlled pore glass to study the ability of this
      material for the separation and preconcentration of Sb(III) and Sb(V). The
      substrate was packed in a minicolumn and incorporated in a flow injection system.
      The effluents of the on-line solid phase extraction (before and after elution)
      were directly coupled to the hydride generation inductively coupled plasma
      optical emission spectrometry system. The effect of pH, sample (and eluent)
      volume, flow rates of sample loading and elution on separation of Sb(III) e Sb(V)
      were evaluated. Our experiments demonstrated that Sb(V) was not retained and it
      was selectively determined during the loading step, while retained Sb(III) was
      determined after elution. The proposed system was also used for the selective
      preconcentration of Sb(III). In this case, a preconcentration factor of 11 and a
      limit of detection of 90 ng L(-1) for Sb(III) were achieved when 8 mL of sample
      were loaded into the column. The speciation analysis of inorganic Sb in river
      water and effluent samples was performed using the proposed method. The values
      obtained for total Sb (obtained by sum of Sb(III) and Sb(V)) were in good
      agreement with expected values. Recoveries of Sb(III) and Sb(V) in the river
      water Standard Reference Material 1640 (from National Institute of Standard and
      Technology) and spiked river waters were between 83 and 111%.

PMID- 18724987
TI  - Covalent binding of sensor phases--a recipe for stable potentials of solid-state
      ion-selective sensors.
AB  - In this work, a new concept of the solid-state sensors free from EMF
      instabilities is proposed. In order to prevent the formation of an aqueous layer
      underneath the ion-selective membrane, instead of improving the hydrophobicity of
      the monolayer, the moieties terminated with acrylate groups were incorporated
      within the redox-active monolayer structure. It allowed to "sew" all phases of
      the sensor (i.e., the transducer, the intermediate layer and the ion-selective
      membrane) and to obtain a stable and durable ion-selective sensor. It is shown
      that newly designed monolayer containing both the ferrocene- and the acrylate
      terminated molecules does not affect the working parameters of the electrode,
      such as selectivity or the slope of the calibration curve, although the EMF drift
      of the sensor is significantly reduced to 0.2 mV per day.

PMID- 18724988
TI  - Evaluation of liquid-liquid microextraction using polypropylene microporous
      membranes for the determination of organophosphorus flame retardants and
      plasticizers in water samples.
AB  - In this work, the suitability of the microporous membrane liquid-liquid
      extraction (MMLLE) technique for the concentration of several organophosphate
      esters (OPs) in water samples is assessed. Analytes were first extracted into a
      few microlitres of an organic solvent, immobilized in the pores of a hollow
      polypropylene membrane, and then determined by gas chromatography with nitrogen
      phosphorus detection (GC-NPD). Main parameters controlling the efficiency of the
      extraction step were identified and their effects on the performance of the
      technique discussed. Under final working conditions, 2 cm long polypropylene
      membranes, containing about 7 microL of octanol in the pores, were dipped in a
      glass vial filled with 115 mL of water with a 30% of sodium chloride. Extractions
      were carried out for 12h, at room temperature, under magnetic stirring. After
      that, analytes were recovered from the membrane with 0.2 mL of ethyl acetate.
      This extract was mixed with the internal standard (50 microL of a tripentyl
      phosphate solution in the same solvent) and finally reduced to ca. 50 microL.
      Overall enrichment factors for the optimized method ranged from 35 to 1400 times,
      and the achieved limits of quantification from 0.008 to 0.12 ng mL(-1), depending
      on the considered compound. Globally, the method showed an acceptable linearity
      and precision for all species, except for tris(2-ethylhexyl) phosphate (TEHP).
      Performance of the MMLLE approach is compared with that reported for other solid-
      and liquid-phase microextraction techniques and its suitability for the analysis
      of real water samples discussed.

PMID- 18724989
TI  - Simultaneous isolation of six fluoroquinolones in serum samples by selective
      molecularly imprinted matrix solid-phase dispersion.
AB  - A simple and sensitive method for the simultaneous determination of six
      fluoroquinolones from serum samples was developed by selective molecularly
      imprinted matrix solid-phase dispersion (MI-MSPD) coupled with chromatographic
      separation. By using ethylene glycol dimethacrylate as crosslinker and
      reformative methanol-water system as reaction medium, the improved water
      compatible imprinted polymers were synthesized which show higher affinity to
      template and its analogues in aqueous environment. The molecularly imprinted
      polymers (MIPs) were applied as the selective dispersant of matrix solid-phase
      dispersion (MSPD) could selectively extracted the six fluoroquinolones from
      serum, while interferences originated from serum matrices were eliminated
      simultaneously. Good linearity was obtained in a range of 0.05-100 microg mL(-1)
      with the correlation coefficients >0.999. The average recoveries of the six
      fluoroquinolones at four different spiked levels (0.25-10 microg mL(-1)) were
      ranged from 72.2% to 114.1% with the relative standard deviations less than 6.6%.
      This method is simple and sensitive, and can be used as an alternative tool to
      the existing HPLC methods for analyzing the residues of fluoroquinolones in
      biological samples.

PMID- 18724990
TI  - Monitoring of sulfonamide antibacterial residues in milk and egg by polymer
      monolith microextraction coupled to hydrophilic interaction chromatography/mass
      spectrometry.
AB  - A simple, rapid, and sensitive method for the determination of traces of thirteen
      sulfonamide antibacterials in milk and eggs is presented. This method is based on
      the combination of polymer monolith microextraction (PMME) technique with
      hydrophilic interaction chromatography/mass spectrometry (HILIC/MS). The
      extraction was performed with a poly(methacrylic acid-ethylene glycol
      dimethacrylate) monolithic capillary column while the subsequent separation was
      carried out on a Luna NH2 column by HILIC. To obtain optimum results, several
      parameters relating to HILIC and PMME were investigated. After optimization,
      acetonitrile (contain 0.05% formic acid, v/v) was used as the elution solution,
      which was well compatible with the mobile phase in HILIC. Good linearities were
      obtained for thirteen SAs with the correlation coefficients (R2) above 0.997. The
      limits of detection (S/N=3) of the method were found to be 0.4-5.7 ng mL(-1) of
      SAs in whole milk and 0.9-9.8 ng g(-1) of SAs in eggs. The recoveries of thirteen
      SAs in two matrices ranged from 80.4 to 119.8%, with relative standard deviations
      less than 11.8%.

PMID- 18724991
TI  - Flow injection-photoinduced-chemiluminescence determination of ziram and zineb.
AB  - A simple, sensitive and rapid method for the determination of the pesticides
      ziram and zineb was described. This new method was based on the coupling of FIA
      methodology and direct chemiluminescent detection; this approach had not been
      used up to now with these pesticides. The additional use of an 'on line'
      photochemical reaction, which was performed by using a photoreactor consisting of
      a long piece of PTFE helically coiled around a 15W low-pressure lamp, increased
      by a factor >20 the chemiluminometric response of the pesticides. An additional 3
      fold improvement in the analytical signal was also achieved by using quinine as
      sensitizer. The obtained throughputs were very high (121 and 101 h(-1) for ziram
      and zineb, respectively); this feature together with its low limit of detection
      (1 ng mL(-1)) makes this method particularly well suited to routine analyses of
      environmental samples. On the other hand, its applicability to two members of the
      dithiocarbamate family of pesticides, makes it promising for the determination of
      the rest of the members of this family. The method was demonstrated by
      application to spiked water samples from different origins (ground, river and
      irrigation).

PMID- 18724992
TI  - A microchip-based flow injection-amperometry system with mercaptopropionic acid
      modified electroless gold microelectrode for the selective determination of
      dopamine.
AB  - A novel chip-based flow injection analysis (FIA) system has been developed for
      automatic, rapid and selective determination of dopamine (DA) in the presence of
      ascorbic acid (AA). The system is composed of a polycarbonate (PC) microfluidic
      chip with an electrochemical detector (ED), a gravity pump, and an automatic
      sample loading and injection unit. The selectivity of the ED was improved by
      modification of the gold working microelectrode, which was fabricated on the PC
      chip by UV-directed electroless gold plating, with a self-assembled monolayer
      (SAM) of 3-mercaptopropionic acid (MPA). Postplating treatment methods for
      cleaning the surface of electroless gold microelectrodes were investigated to
      ensure the formation of high quality SAMs. The effects of detection potential,
      flow rate, and sampling volume on the performance of the chip-based FIA system
      were studied. Under optimum conditions, a detection limit of 74 nmol L(-1) for DA
      was achieved at the sample throughput rate of 180 h(-1). A RSD of 0.9% for peak
      heights was observed for 19 runs of a 100 micromol L(-1) DA solution.
      Interference-free determination of DA could be conducted if the concentration
      ratio of AA-DA was no more than 10.

PMID- 18724993
TI  - Multiresidue determination of triarylmethane and phenothiazine dyes in fish
      tissues by LC-MS/MS.
AB  - The occurrence of residues of malachite green and its leuco-metabolite in tissues
      of farmed fish for human consumption have long been of concern and there is
      extensive literature on methods of analysis and surveillance for these compounds.
      Recently, concern has been expressed that the use of other related compounds in
      place of malachite green may go undetected. This paper describes a new method for
      extending the range of triarylmethane and related phenothiazine dyes that can be
      detected in fish. In this procedure 13 parent compounds are monitored, with any
      potential leuco-forms being oxidized back to the parent prior to determination.
      The method utilizes a buffer-acetonitrile extraction followed by liquid-liquid
      extraction. Oxidant is added and the extracts further purified by cation exchange
      chromatography. Final determination is carried out using LC-MS/MS. The method has
      been validated to the standards of Commission Decision 2002/657/EC.

PMID- 18724994
TI  - Fluorescence enhancement effect for the determination of DNA with calcein-cetyl
      trimethyl ammonium bromide system.
AB  - A new spectrofluorimetric method was developed for the determination of trace
      amounts of DNA using the calcein as a fluorescent probe. In the presence of
      appropriate amounts of the cationic surfactant cetyl trimethyl ammonium bromide
      (CTAB), the anionic dye calcein dimerizes. The weak fluorescence intensity of the
      dimer was enhanced by adding DNA at pH 6-7. The interaction between calcein-CTAB
      and DNA was studied on the basis of this behavior and a new method was developed
      for determining DNA. Under the optimal conditions, the enhanced fluorescence
      intensity was in proportion to the concentration of DNA in the range of 4.0x10(
      6) to 8.0x10(-5) g L(-1) for fsDNA and thermally denatured ctDNA (4.5x10(-6) to
      9.0x10(-5) g L(-1)). The detection limits (S/N=3) were 2.0x10(-6) and 2.2x10(-6)
      g L(-1), respectively. This method was used for determining the concentration of
      DNA in synthetic samples with satisfactory results.

PMID- 18724995
TI  - Anti-Her-2 monoclonal antibody conjugated polymer fluorescent nanoparticles probe
      for ovarian cancer imaging.
AB  - Fluorescent nanoparticles (FNPs) with unique optical properties may be useful as
      biosensors in living cancer cell imaging and cancer targeting. A novel kind of
      polymer fluorescent nanoparticles (PFNPs) was synthesized and its application for
      ovarian cancer imaging with fluorescence microscopy imaging technology was
      presented in this study. The PFNPs were synthesized with precipitation
      polymerization by using methacrylic acid (MAA) as monomer, trimethylolpropane
      trimethacrylate (Trim) as cross-linker, azobisisobutyronitrile (AIBN) as radical
      initiator and butyl rhodamine B (BTRB) as fluorescent dye. And the fluorescent
      dye was embedded into the three-dimensional network of the polymer when the
      polymer was produced. With this method the PFNPs can be prepared easily. And then
      the PFNPs were successfully modified with anti-Her-2 monoclonal antibody. The
      fluorescence probe based on anti-Her-2 monoclonal antibody conjugated PFNPs has
      been used to detect ovarian cancer cells with fluorescence microscopy imaging
      technology. The experimental results demonstrate that the anti-Her-2 monoclonal
      antibody conjugated PFNPs can effectively recognize ovarian cancer cells and
      exhibit good sensitivity and exceptional photostability, which would provide a
      novel way for the diagnosis and curative effect observation of ovarian cancer
      cells.

PMID- 18724996
TI  - Computer screen photo-excited surface plasmon resonance imaging.
AB  - Angle and spectra resolved surface plasmon resonance (SPR) images of gold and
      silver thin films with protein deposits is demonstrated using a regular computer
      screen as light source and a web camera as detector. The screen provides multiple
      angle illumination, p-polarized light and controlled spectral radiances to excite
      surface plasmons in a Kretchmann configuration. A model of the SPR reflectances
      incorporating the particularities of the source and detector explain the observed
      signals and the generation of distinctive SPR landscapes is demonstrated. The
      sensitivity and resolution of the method, determined in air and solution, are
      0.145 nm pixel(-1), 0.523 nm, 5.13x10(-3) RIU degree(-1) and 6.014x10(-4) RIU,
      respectively, encouraging results at this proof of concept stage and considering
      the ubiquity of the instrumentation.

PMID- 18724997
TI  - Differential scanning calorimetry: a potential tool for discrimination of olive
      oil commercial categories.
AB  - Differential scanning calorimetry thermograms of five commercial categories of
      olive oils (extra virgin olive oil, olive oil, refined olive oil, olive-pomace
      oil and refined olive-pomace oil) were performed in both cooling and heating
      regimes. Overlapping transitions were resolved by deconvolution analysis and all
      thermal properties were related to major (triacylglycerols, total fatty acids)
      and minor (diacylglycerols, lipid oxidation products) chemical components. All
      oils showed two well distinguishable exothermic events upon cooling.
      Crystallization enthalpies were significantly lower in olive oils due to a more
      ordered crystal structure, which may be related to the higher triolein content.
      Pomace oils exhibited a significantly higher crystallization onset temperature
      and a larger transition range, possibly associated to the higher amount of
      diacylglycerols. Heating thermograms were more complex: all oils exhibited
      complex exo- and endothermic transitions that could differentiate samples
      especially with respect to the highest temperature endotherm. These preliminary
      results suggest that both cooling and heating thermograms obtained by means of
      differential scanning calorimetry may be useful for discriminating among olive
      oils of different commercial categories.

PMID- 18724998
TI  - Brain stimulation, revolutions, and the shifting time domain of depression.

PMID- 18724999
TI  - Approach to chest pain: noncardiac and angina. Foreword.

PMID- 18725000
TI  - Approach to chest pain: noncardiac and angina. Introduction.

PMID- 18725001
TI  - Classification, natural history, epidemiology, and risk factors of noncardiac
      chest pain.

PMID- 18725002
TI  - Health care seeking behaviors, psychological factors, and quality of life of
      noncardiac chest pain.

PMID- 18725003
TI  - Chest pain units.

PMID- 18725004
TI  - Pathophysiology of noncardiac chest pain: not only acid.

PMID- 18725005
TI  - Evaluation and diagnosis of noncardiac chest pain.

PMID- 18725006
TI  - Treatment of non-cardiac chest pain.

PMID- 18725007
TI  - Chronic stable angina pectoris.

PMID- 18725008
TI  - Quiz page September 2008: progressive paraplegia in a long-term hemodialysis
      patient. Brown tumor compressing the thoracic spinal column.

PMID- 18725009
TI  - Practicable frequent hemodialysis: a proposal to meet the needs of patients and
      the requirements of Medicare.

PMID- 18725010
TI  - Statins for slowing kidney disease progression: an as yet unproven indication.

PMID- 18725011
TI  - NGAL in acute kidney injury: from serendipity to utility.

PMID- 18725012
TI  - Improving outcomes in hemodialysis patients: the need for well-designed clinical
      trials.

PMID- 18725013
TI  - "Artificial" hemodialysis versus "natural" hemofiltration.

PMID- 18725014
TI  - A population-based screening for microalbuminuria among relatives of CKD
      patients: the Kidney Evaluation and Awareness Program in Sheffield (KEAPS).
AB  - BACKGROUND: Microalbuminuria has been used to detect subjects at risk of
      cardiovascular disease and chronic kidney disease (CKD) in patients with
      diabetes, those with hypertension, and the general population. However, relatives
      of patients with CKD have not been investigated for microalbuminuria in the
      United Kingdom. STUDY DESIGN: A cross-sectional study evaluating the prevalence
      of microalbuminuria in relatives of patients with CKD compared with the general
      population of Sheffield, England. SETTING & PARTICIPANTS: Participants in the
      Kidney Evaluation and Awareness Program in Sheffield, a population-based
      screening program for microalbuminuria. 274 relatives of patients with CKD were
      studied and compared with an age- and sex-matched control group from the general
      population. PREDICTOR: Family history of CKD. MEASUREMENT & OUTCOMES: Screening
      tools included a questionnaire collating information for demographics, lifestyle,
      and medical and family history of diabetes, hypertension, and CKD. Urine samples
      were collected for microalbuminuria estimation. Microalbuminuria measurements
      were obtained by using immunonephelometry. Microalbuminuria thresholds were
      defined using albumin-creatinine ratio. RESULTS: The prevalence of
      microalbuminuria was 9.5% in those with a family history of CKD. This was
      significantly greater than the prevalence of 1.4% in the age- and sex-matched
      control group with no family history of CKD (P = 0.001). Independent determinants
      of microalbuminuria in the study population in an adjusted logistic regression
      model were family history of diabetes (odds ratio [OR], 2.88; 95% confidence
      interval, 1.17 to 7.04), obesity (OR, 3.29; 95% confidence interval, 1.61 to
      6.69), and family history of CKD (OR, 6.96; 95% confidence interval, 3.48 to
      13.92). LIMITATIONS: Cross-sectional snapshot analysis, microalbuminuria measured
      once. CONCLUSIONS: The prevalence of microalbuminuria in relatives of patients
      with CKD is greater than in an age- and sex-matched control group from the
      general population. The prognostic value of microalbuminuria in this category of
      at-risk population remains to be determined in longitudinal studies.

PMID- 18725015
TI  - A systematic review of kidney transplantation from expanded criteria donors.
AB  - BACKGROUND: During the past few years, there has been renewed interest in the use
      of expanded criteria donors (ECD) for kidney transplantation to increase the
      numbers of deceased donor kidneys available. More kidney transplants would result
      in shorter waiting times and limit the morbidity and mortality associated with
      long-term dialysis therapy. STUDY DESIGN: Systematic review of the literature.
      SETTING & POPULATION: Kidney transplantation population. SELECTION CRITERIA FOR
      STUDIES: Studies were identified by using a comprehensive search through MEDLINE
      and EMBASE databases. Inclusion criteria were case series, cohort studies, and
      randomized controlled trials assessing kidney transplantation in adult recipients
      using ECDs. PREDICTOR: A special focus was given to studies comparing the
      evolution of kidney transplantation between standard criteria donors (defined as
      a donor who does not meet criteria for donation after cardiac death or ECD) and
      ECDs (defined as any brain-dead donor aged > 60 years or a donor aged > 50 years
      with 2 of the following conditions: history of hypertension, terminal serum
      creatinine level >or= 1.5 mg/dL, or death resulting from a cerebrovascular
      accident). OUTCOMES: Criteria used to define and select ECDs, practice patterns,
      long-term outcomes, early complications, and some patient issues, such as
      selection criteria and immunosuppressive management. RESULTS: ECD kidneys have
      worse long-term survival than standard criteria donor kidneys. The optimal ECD
      kidney for donation depends on adequate glomerular filtration rate and acceptable
      donor kidney histological characteristics, albeit the usefulness of biopsy is
      debated. LIMITATIONS: This review is based mainly on data from observational
      studies, and varying amounts of bias could be present. We did not attempt to
      quantitatively analyze the effect of ECD kidneys on kidney transplantation
      because of the huge heterogeneity found in study designs and definitions of ECD.
      CONCLUSIONS: Based on the available evidence, we conclude that patients younger
      than 40 years or scheduled for kidney retransplantation should not receive an ECD
      kidney. Patients 40 years or older, especially with diabetic nephropathy or
      nondiabetic disease, but a long expected waiting time for kidney transplantation,
      show better survival receiving an ECD kidney than remaining on dialysis therapy.

PMID- 18725016
TI  - Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) is a protein belonging to the
      lipocalin superfamily initially found in activated neutrophils, in accordance
      with its role as an innate antibacterial factor. However, it subsequently was
      shown that many other types of cells, including in the kidney tubule, may produce
      NGAL in response to various injuries. The increase in NGAL production and release
      from tubular cells after harmful stimuli of various kinds may have self-defensive
      intent based on the activation of specific iron-dependent pathways, which in all
      probability also represent the mechanism through which NGAL promotes kidney
      growth and differentiation. NGAL levels predict the future appearance of acute
      kidney injury after treatments potentially detrimental to the kidney and even the
      acute worsening of unstable nephropathies. Furthermore, recent evidence also
      suggests that NGAL somehow may be involved in the pathophysiological process of
      chronic renal diseases, such as polycystic kidney disease and glomerulonephritis.
      NGAL levels clearly correlate with severity of renal impairment, probably
      expressing the degree of active damage underlying the chronic condition. For all
      these reasons, NGAL may become one of the most promising next-generation
      biomarkers in clinical nephrology and beyond.

PMID- 18725017
TI  - Balkan nephropathy: evolution of our knowledge.
AB  - Balkan endemic nephropathy (BEN), originally described in the late 1950s as a
      chronic tubulointerstitial kidney disease, is identified by its unique
      epidemiological features. The most remarkable characteristic of BEN is the focal
      topographical nature that characterizes its occurrence at the global, national,
      and even household level. BEN affects only certain endemic rural foci along
      tributaries of the Danube River in the Balkan countries of Bosnia, Bulgaria,
      Croatia, Romania, and Serbia. The spatial distribution has remained astonishingly
      unchanged with time because the disease affects the same endemic clusters as 50
      years ago. The natural course of the disease is characterized by universal
      development of end-stage renal disease and the frequent development of upper
      urinary tract tumors, posing a substantial disease burden to the afflicted areas.
      The greatest challenge in the study of BEN has been the elucidation of its cause.
      The unique features of the disease, in particular its endemic nature and the long
      incubation period required for the disease to develop, have led to the proposal
      that BEN represents a unique environmental disease. The quest for the responsible
      environmental factor has been long and diverse, and although no definitive answer
      has been provided to date, converging lines of evidence support the theory that
      long-term consumption of food contaminated with aristolochic acid underlies the
      pathogenesis of BEN. The present review describes the evolution of our knowledge
      of BEN in relation to the development of the main theories for its pathogenesis.

PMID- 18725018
TI  - Remission of aseptic inflammatory ascites after nephrectomy of a failed
      allograft.

PMID- 18725019
TI  - The TREAT study answers a question, not the question.

PMID- 18725022
TI  - Vascular access surveillance: no benefit?

PMID- 18725024
TI  - Osmotic nephrosis and contrast media.

PMID- 18725025
TI  - Urothelial carcinoma in kidney transplant recipients: conversion from calcineurin
      inhibitor to proliferation signal inhibitor?

PMID- 18725027
TI  - Safety of outpatient kidney biopsy: one center's experience with 178 native
      kidney biopsies.

PMID- 18725028
TI  - Hypersensitivity to inulin: a rare and mostly benign event.

PMID- 18725029
TI  - The role of HIV infection and drug and alcohol dependence in hospital mortality
      among critically ill patients.
AB  - PURPOSE: Critical care outcomes among HIV-infected patients have improved because
      of advances in HIV therapy and general improvements in intensive care unit (ICU)
      management. There is a high co-occurrence of drug and alcohol dependence among
      HIV-infected patients, and the independent role of drug and alcohol dependence
      among patients with and without HIV infection in outcomes of critical illness is
      unclear. MATERIALS AND METHODS: We analyzed a prospectively collected database of
      7015 index ICU admissions at 2 teaching hospitals between January 1999 and
      January 2006. The ICU diagnoses were determined from prospective chart review and
      classified according to the dictionary of diagnoses developed by the Intensive
      Care National Audit and Research Council. We used logistic regression to
      determine the independent association of drug and alcohol dependence as well as
      HIV infection with in-hospital mortality. Covariates that were adjusted for
      included acute drug overdose, Acute Physiology and Chronic Health Evaluation II
      score, age, sex, hospital site, and socioeconomic variables. RESULTS: Of all
      patients, 4.4% (309 of 7015) were HIV infected; and of these, 56% (173 of 309)
      had a history of drug and alcohol dependence, whereas only 7.4% (502 of 6706) of
      the HIV-negative group had a history of drug and alcohol dependence. Drug and
      alcohol dependence was not independently associated with hospital mortality in
      either the model including all admissions (adjusted odds ratio [AOR] 0.80; 95%
      confidence interval [CI] 0.62-1.03) or the model including pneumonia and sepsis
      admissions only (AOR 0.92; 95% CI 0.59-1.41). Infection with HIV was
      independently associated with hospital mortality (AOR 2.16; 95% CI 1.60-2.93).
      CONCLUSIONS: Although HIV infection is associated with increased hospital
      mortality, drug and alcohol dependence is not associated with an increased
      hospital mortality independent of HIV infection.

PMID- 18725030
TI  - Families' interactions with physicians in the intensive care unit: the impact on
      family's satisfaction.
AB  - PURPOSE: The objective of this study is to correlate the levels of satisfaction
      of family members, with their perception of the way information was offered and
      assistance delivered during the patient's stay in the intensive care unit (ICU).
      MATERIALS AND METHODS: This is a prospective study conducted in a 13-bed mixed
      ICU in a tertiary cancer. Family members were enrolled 2 days after admission if
      the patient remained in the ICU. Questions derived from a previous study assessed
      the quality of the information and support received (Crit Care Med 1998;
      26:1187). To generate the satisfaction criteria, families fulfilled a Portuguese
      version of the Critical Care Family Needs Inventory. RESULTS: One hundred sixty
      four families were interviewed between May 2002 and May 2003. Insufficient
      information concerning the consequences of disease was a determinant of
      dissatisfaction (odds ratio [OR], 3.35; confidence interval [CI], 1.3-8.8), as
      well as insufficient information given by the ICU doctors (OR, 3.85; CI, 1.2
      12.2). Accessibility of doctors was a major determinant of dissatisfaction when
      considered inadequate (OR, 6.92; CI, 2.3-20.6), and it was associated to a
      conflict regarding prognosis (P = .017). CONCLUSION: Family satisfaction and
      understanding in the ICU may improve if the doctors are more accessible to
      provide information and the staff strive to better explain the patient's
      condition.

PMID- 18725031
TI  - The role of transport intervals in outcomes for critically ill patients who are
      transferred to referral centers.
AB  - PURPOSE: The aim of this study was to determine the association between transport
      intervals (including time from call to arrival of transport team at the sending
      hospital, time spent by the transport team in the sending hospital, and transport
      time between the sending and receiving hospital) and intensive care unit (ICU)
      and hospital length of stay and hospital mortality at the receiving hospital.
      MATERIALS AND METHODS: This was a retrospective, stratified cohort study
      involving all patients 15 years and older who were transferred from one hospital
      to another of equal or larger size in British Columbia, Canada, and who spent at
      least 1 day in an ICU or coronary care unit (CCU) at the receiving hospital
      during 1999 (n = 1930). Data were obtained from 6 administrative databases and
      linked using generalized software. RESULTS: After adjustment for age, sex,
      comorbidity, and diagnostic group, longer time from call to arrival of paramedics
      at the sending hospital was associated with a shorter length of ICU/CCU stay
      (rate ratio [RR], 0.91; 95% confidence interval [CI], 0.86-0.97) for survivors
      and a longer length of hospital (RR, 1.12; 95% CI, 1.05-1.21) and ICU/CCU (RR,
      1.14; 95% CI, 1.04-1.25) stay for nonsurvivors in the higher-priority air
      transport group, and with a slightly shorter length of hospital stay (RR, 0.97;
      95% CI, 0.95-0.99) for all patients in the lower-priority air transport group.
      Longer time spent by paramedics at the sending hospital was associated with a
      shorter length of hospital stay (RR, 0.79; 95% CI, 0.65-0.96) for survivors in
      the higher-priority air transport group. Longer time for transport between the
      sending and receiving hospitals was associated with a longer length of ICU/CCU
      stay (RR, 1.69; 95% CI, 1.26-2.27) for survivors in the higher-priority air
      transport group but a slightly shorter length of ICU/CCU stay (RR, 0.97; 95% CI,
      0.95-0.99) for all patients in the ground transport group. There were no
      associations between transport times and hospital mortality. CONCLUSIONS:
      Transport intervals are independently associated with ICU/CCU and hospital
      lengths of stay at the receiving hospital for critically ill adults transferred
      to referral centers.

PMID- 18725032
TI  - Analysis of risk factors associated with complications of hyperbaric oxygen
      therapy.
AB  - PURPOSE: The aim of this study was to verify independent risk factors of pressure
      equalization problems associated with hyperbaric oxygen (HBO(2)) therapy.
      METHODS: We reviewed a single-institutional study of 1609 patients with 17604
      treatments who had HBO(2) therapy in a multiplace chamber, in which the factors
      examined and their relationship to complications were assessed, using
      multivariate analyses, to determine the significantly independent risk factors of
      complications related to HBO(2) therapy. RESULTS: The compression rate was 0.067
      atmospheres absolute/min (6.8 kPa/min). Pressure equalization problems of the
      middle ear, expressed as pain or discomfort, such as cranial sinus pain, and
      teeth pain were observed in 156 patients (9.7%). Sixty-six of them could not
      continue HBO(2) therapy because of these problems. Peripheral circulatory
      disorders with refractory ulcers or nonhealing wounds and the interval between
      clinical symptoms and the first day of HBO(2) therapy were independent risk
      factors of pressure equalization problems. Independent risk factors of cessation
      due to pressure equalization problems were identified as age more than 61 years,
      female sex, and interval between symptoms and the first day of HBO(2) therapy.
      CONCLUSION: It is suggested that chamber compression must be performed with
      particular care when patients have peripheral circulatory disorders and have
      short interval between clinical symptoms and the first day of HBO(2) therapy.

PMID- 18725033
TI  - Factors predicting adherence to the Canadian Clinical Practice Guidelines for
      nutrition support in mechanically ventilated, critically ill adult patients.
AB  - PURPOSE: The aim of this study was to determine factors that are associated with
      adherence to the Canadian nutrition support clinical practice guidelines (CPGs).
      MATERIALS AND METHODS: We conducted a secondary analysis of data from a
      prospective observational cohort study of nutrition support practices in 58
      intensive care units (ICUs) across Canada, grouped into 50 clusters. Adequacy of
      enteral nutrition (EN) (energy received from EN / energy prescribed by the
      dietitian x 100), was used as a marker of adherence to the guidelines. We applied
      hierarchical modeling techniques to examine the impact of various hospital, ICU,
      and patient factors on EN adequacy. RESULTS: The overall average EN adequacy was
      51.3% (SE, 1.8%). In a multiple regression analysis, after adjusting for varying
      days of observation, hospital type (academic 54.3% vs community 45.2%, P < .001),
      admission category of the patient (medical 60.2% vs surgical 39.2%, P < .001),
      and sex of the patient (male 46.5% vs female 52.8%, P < .001) were found to be
      significant predictors of EN adequacy and adherence to the Canadian nutrition
      support CPGs. CONCLUSIONS: Specific hospital, ICU, and patient characteristics
      influence adherence to the Canadian nutrition support CPGs. Further research is
      required to illuminate the mechanisms by which female and surgical patients and
      community hospitals lead to lower guideline adherence.

PMID- 18725034
TI  - The importance of differentiating between elective and emergency postoperative
      critical care patients.
AB  - PURPOSE: The purpose of the study is to demonstrate the importance of separately
      analyzing data on elective and emergency surgery patients admitted
      postoperatively to intensive and intermediate care units. MATERIALS AND METHODS:
      A prospective observational study was performed in a tertiary care university
      hospital to assess the demographic and clinical differences between emergency and
      elective surgical patients (>14 years old). Group 1 included patients transferred
      to a floor bed or the ambulatory surgery unit for discharge home after a short
      stay (<12 hours) in the postanesthesia care unit. Group 2 patients were admitted
      to the cardiothoracic intensive care unit (ICU), neurosurgical ICU, general ICU,
      or for an extended intermediate care postanesthesia care unit stay (>12 hours).
      RESULTS: In groups 1 (n = 1059), there were significant differences between the
      elective and emergency patients. Emergency, as compared with elective group 2 (n=
      1883) patients, experienced more severe preexisting illnesses (ie, had higher
      American Society of Anesthesiology classifications), underwent different and
      shorter operations, required prolonged postoperative mechanical ventilation,
      required longer ICU stays, and had higher mortality. CONCLUSIONS: Substantial
      differences between elective and emergency surgery patients have important
      implications when conducting and reporting research on the nature, extent, and
      outcome of postoperative ICU care.

PMID- 18725035
TI  - Hospital mortality among adults admitted to and discharged from intensive care on
      weekends and evenings.
AB  - PURPOSE: Patient care may be inconsistent during off hours. We sought to
      determine whether adults admitted to or discharged from intensive care units
      (ICUs) on evenings and weekends have increased mortality rates. MATERIALS AND
      METHODS: All adults admitted to ICUs in the Calgary Health Region, Alberta,
      Canada, during 2000 to 2006 were included. The in-hospital mortality risk was
      assessed with admissions or discharges on weekdays (Monday to Friday) and daytime
      (8:00 am to 5:59 pm) as compared with weekends (Saturday and Sunday) and nights
      (6:00 pm to 7:59 am). RESULTS: Intensive care unit admissions (n = 20466)
      occurred during weekends in 18%, nights in 41%, and nights and/or weekends in
      49%. Among the 17864 survivors to ICU discharge, 26% were discharged on weekends,
      21% at night, and 41% on nights and/or weekends. Increased crude mortality rates
      were associated with both admission (24% vs 14%, P < .0001) and discharge (12% vs
      5%, P < .0001) during nights as compared with days. Admission to (26% vs 16%, P <
      .0001) but not discharge from (6% vs 7%, P = .42) ICU during weekends as compared
      with weekdays was associated with increased mortality. After controlling for
      confounding variables using logistic regression analyses, neither weekend
      admission nor discharge was associated with death. However, both night admission
      and discharge were independently associated with mortality. CONCLUSIONS: Our
      observations of excess risk associated with admission to or discharge from ICU at
      night merits further exploration as to whether it may reflect inconsistencies in
      care after hours.

PMID- 18725036
TI  - Characteristics and outcomes of patients receiving a medical emergency team
      review for respiratory distress or hypotension.
AB  - PURPOSE: To describe the characteristics and outcomes of patients receiving a
      medical emergency team (MET) review for the MET syndromes of respiratory distress
      or hypotension and to assess the effect of delayed MET activation on their
      outcomes. MATERIALS AND METHODS: We retrospectively analyzed the medical records
      of 2 cohorts of 100 patients for each of the MET syndromes of respiratory
      distress and hypotension. We collected information on patient demographics,
      comorbidities, presence of sepsis, and patient outcome. We documented the
      presence and duration of delayed MET activation. RESULTS: Patients with
      respiratory distress were more likely to be postoperative (40% vs 28%, P = .07),
      but less likely to have a history of congestive cardiac failure (12% vs 22%, P =
      .06). Sepsis was present in 58% of cases. The hospital mortality for MET calls
      due to respiratory distress and hypotension was 38% and 35%, respectively (P =
      .77). Delayed MET calls occurred in 50% of patients with the MET syndrome of
      respiratory distress and in 39% of those with hypotension (P = .11). The median
      duration of delay was 12 hours in patients with respiratory distress compared to
      5 hours for patients with hypotension (P = .016). A delay in making a MET call
      was associated with an increase in mortality (odds ratio, 2.10; 95% confidence
      interval, 1.01-4.34; P = .045). CONCLUSIONS: Patients receiving MET calls for
      respiratory distress or hypotension were elderly and had a mortality greater than
      35%. In many cases, MET activation was delayed. This delay was associated with
      increased mortality.

PMID- 18725037
TI  - District nurses' attitudes toward patient consent: the case of mechanical
      ventilation on amyotrophic lateral sclerosis patients: results from a French
      national survey.
AB  - PURPOSE: In France, a recent law emphasizes patient rights and prohibits unwanted
      therapies in end-of-life care. As end-of-life home care is increasing, we aimed
      to assess French district nurses' attitudes toward terminally ill patients'
      autonomy. MATERIALS AND METHODS: We used data from a nationwide telephone survey
      conducted in 2005 among a random sample of French district nurses (n = 602).
      Nurses' attitudes were assessed with a clinical case describing a patient
      (randomly defined as a male or a female aged 50 years) having amyotrophic lateral
      sclerosis (ALS) who urgently needs mechanical ventilation. Nurses were asked
      whether patient consent was necessary before performing intubation/tracheotomy,
      and the analysis took into account various covariates, including nurses'
      religiosity, nurses' attitudes toward living wills, and patient sex. RESULTS:
      Overall, 44% of nurses considered that an ALS patient with respiratory failure
      should always be intubated (53% for a female patient, 40% for a male patient, P <
      .01), and after intubation, 27% upheld tracheotomy without considering patient
      consent as a necessary prerequisite (39% among male nurses, 30% among female
      nurses, P < .05). Poor communication with terminal patients and hostility toward
      living will were also predictive of willingness to perform both mechanical
      ventilation and tracheotomy without patient consent. CONCLUSIONS: A significant
      part of French district nurses may have a disturbing propensity to support
      intubation and tracheotomy with insufficient attention paid to the patient's
      will. Further research should investigate potential causal factors (such as
      increased workload) as well as sex-related attitudes in nurse-patient
      relationship.

PMID- 18725038
TI  - Modeling in-hospital patient survival during the first 28 days after intensive
      care unit admission: a prognostic model for clinical trials in general critically
      ill patients.
AB  - OBJECTIVE: The objective of the study was to develop a model for estimating
      patient 28-day in-hospital mortality using 2 different statistical approaches.
      DESIGN: The study was designed to develop an outcome prediction model for 28-day
      in-hospital mortality using (a) logistic regression with random effects and (b) a
      multilevel Cox proportional hazards model. SETTING: The study involved 305
      intensive care units (ICUs) from the basic Simplified Acute Physiology Score
      (SAPS) 3 cohort. PATIENTS AND PARTICIPANTS: Patients (n = 17138) were from the
      SAPS 3 database with follow-up data pertaining to the first 28 days in hospital
      after ICU admission. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The database
      was divided randomly into 5 roughly equal-sized parts (at the ICU level). It was
      thus possible to run the model-building procedure 5 times, each time taking four
      fifths of the sample as a development set and the remaining fifth as the
      validation set. At 28 days after ICU admission, 19.98% of the patients were still
      in the hospital. Because of the different sampling space and outcome variables,
      both models presented a better fit in this sample than did the SAPS 3 admission
      score calibrated to vital status at hospital discharge, both on the general
      population and in major subgroups. CONCLUSIONS: Both statistical methods can be
      used to model the 28-day in-hospital mortality better than the SAPS 3 admission
      model. However, because the logistic regression approach is specifically designed
      to forecast 28-day mortality, and given the high uncertainty associated with the
      assumption of the proportionality of risks in the Cox model, the logistic
      regression approach proved to be superior.

PMID- 18725039
TI  - Conscious sedation in the critically ill ventilated patient.
AB  - PURPOSE: The aim of sedation is to provide comfort and minimize anxiety. However,
      adverse effects are noteworthy, and the optimal end point of sedation in
      intensive care unit patients is still debated. We analyzed if a level 2 on the
      Ramsay Scale (ie, awake, cooperative, oriented, tranquil patient) is suitable for
      an invasive therapeutic approach. MATERIALS AND METHODS: Forty-two patients
      requiring respiratory support and sedation for at least 4 days were enrolled in a
      prospective interventional cohort study aiming at maintaining patients awake and
      collaborative. The Ramsay score was recorded 3 times a day. Once a day, the nurse
      in charge evaluated adequacy of sedation according to the compliance with nursing
      care and therapeutic maneuvers in the previous 24 hours. Data were collected
      until patients were ventilated. RESULTS: Overall, 264 of 582 days were classified
      as conscious. Sedation was adequate in 93.9% of them. In conscious days, a higher
      Simplified Acute Physiology Score II score and male sex significantly correlated
      with inadequate sedation. CONCLUSIONS: In a population of severe intensive care
      unit patients, conscious sedation was achieved in almost half of the days spent
      on ventilation. The positive implications (eg, on length of weaning and cost of
      sedation) of a conservative sedation strategy may be highly relevant.

PMID- 18725040
TI  - Starling's equation and bedside critical care.

PMID- 18725041
TI  - Discrepancy between inferior vena cava and right atrial oxygen saturations as a
      sign of ischemia in the mesenteric circulation.
AB  - We describe the case of a 72-year-old patient admitted to intensive care
      following abdominal surgery. Venous oxygen saturations from the right atrium and
      superior vena cava (SVC) showed large variation due to ongoing ischemia in the
      mesentric circulation. If trends in venous oxygen saturation are to be followed,
      serial samples must be taken from the same central venous catheter (CVC) port.

PMID- 18725042
TI  - Reducing pain in patients undergoing cardiac surgery after implementation of a
      quality improvement postoperative pain treatment program.
AB  - PURPOSE: The aim of this study was to test the effectiveness of a quality
      improvement postoperative pain treatment program after cardiac surgery. MATERIALS
      AND METHODS: This was a prospective, quasiexperimental study using nonequivalent
      groups comprising 3 periods: baseline (group baseline), implementation of the
      algorithm for acute pain management, and reassessment (group reassessment).
      Inclusion of 133 patients after elective cardiac surgery at an 18-bed surgical
      intensive care unit (SICU) at a Swiss university hospital. The algorithm was
      implemented by training, pocket guidelines, regular audits, and feedback. The
      implementation period was completed when the adherence to 2 of 3 process
      indicators attained at least 70% over 2 months. Visual analog scales (VAS) for
      pain, morphine consumption, pain perception, and sleep quality were assessed
      during stay in SICU and after 1 month and 6 months. RESULTS: The assessment
      included 79 patients at baseline and 54 in the reassessment periods. Pain
      intensity at rest decreased from 2.7 +/- 1.4 to 2.2 +/- 1.4 cm (VAS; P = .008).
      Retrospective perception of pain intensity at rest decreased from 3.8 +/- 2.2 to
      2.6 +/- 1.8 (P = .004). The proportion of patients with no pain or often without
      pain increased from 11% to 37% (P = .005). The number of patients with sleep
      disturbances decreased from 68% to 35% (P = .012). No differences were observed
      at 1 and 6 months postoperatively. CONCLUSIONS: After algorithm implementation in
      the SICU, pain intensity at rest decreased and quality of sleep improved.

PMID- 18725043
TI  - Risk factors for the development of early-onset delirium and the subsequent
      clinical outcome in mechanically ventilated patients.
AB  - OBJECTIVES: The aim of the study was to investigate the risk factors of
      developing early-onset delirium in mechanically ventilated patients and determine
      the subsequent clinical outcomes. METHODS: Confusion assessment method for the
      intensive care unit (ICU) was used to assess the enrolled mechanically ventilated
      patients for delirium. The risk factors of developing delirium and clinical
      outcomes were determined in these subjects. RESULTS: Delirium was present in 31
      (21.7%) of 143 patients in the first 5 days. In multivariable analysis,
      hypoalbuminemia (odds ratio, 5.94; 95% confidence interval, 1.23-28.77) and
      sepsis (odds ratio, 3.65; 95% confidence interval, 1.03-12.9) increased the risk
      of developing delirium in mechanically ventilated patients. The patients with
      delirium had a higher in-hospital mortality (67.7% vs 33.9%, respectively; P =
      .001) and longer duration of mechanical ventilation (19.5 +/- 15.8 vs 9.3 +/- 8.8
      days, respectively; P = .003) than patients without delirium. The incidence of
      nosocomial pneumonia was increased in delirious patients (64.5% vs 38.4%, P =
      .01) compared with nondelirious patients, whereas the lengths of ICU or hospital
      stay were similar between both groups. CONCLUSIONS: Mechanically ventilated
      patients with sepsis or hypoalbuminemia were more vulnerable to develop delirium
      in their early stay in the ICU. Early-onset delirium is associated with prolonged
      duration of mechanical ventilation and higher incidence of nosocomial pneumonia,
      leading to a higher mortality.

PMID- 18725044
TI  - Investigation of heart rate and blood pressure variability, baroreflex
      sensitivity, and approximate entropy in acute brain injury patients.
AB  - PURPOSE: The purpose of the study was to investigate longitudinally over time
      heart rate (HR) and blood pressure variability and baroreflex sensitivity in
      acute brain injury patients and relate them with the severity of neurologic
      dysfunction and outcome. METHODS: Data from 20 brain injured patients due to
      multiple causes and treated in the intensive care unit were used, with HR and
      blood pressure recorded from monitors and analyzed on a daily basis. We performed
      power spectral analysis estimating low frequencies (LF: 0.04-0.15 Hz), high
      frequencies (HF: 0.15-0.4 Hz), and their ratio and calculated the approximate
      entropy, which assesses periodicity within a signal and transfer function (TF),
      that estimates baroreflex sensitivity. Heart rate variance was considered as a
      measure of HR variability. RESULTS: Nonsurvivors (brain dead) had lower
      approximate entropy (0.65 +/- 0.24 vs 0.84 +/- 0.26, P < .05) and lower variance
      mean values (0.48 +/- 0.54 vs 1.29 +/- 0.42 ms(2)/Hz, P < .01), lower LF and HF
      minimum values (0.31 +/- 0.88 vs 1.11 +/- 0.46, P < .01; and 0.27 +/- 0.42 vs
      0.86 +/- 0.30, P < .01, respectively), lower LF/HF (0.22 +/- 0.29 vs 0.62 +/-
      0.28, P < .01), and lower TF mean values (0.43 +/- 0.29 vs 1.11 +/- 0.74, P <
      .05) during their whole stay in the intensive care unit in relation with
      survivors. The mean variance (P < .05), mean TF (P < .05), and mean LF/HF (P <
      .05) were significantly successful in separating survivors from nonsurvivors.
      CONCLUSIONS: We conclude that in acute brain injury patients, low variability,
      low baroreflex sensitivity, and sustained decrease in LF/HF of HR signals are
      linked with a high mortality rate.

PMID- 18725045
TI  - Early decompressive craniectomy for patients with severe traumatic brain injury
      and refractory intracranial hypertension--a pilot randomized trial.
AB  - PURPOSE: The aims of this study were to test the feasibility and to assess
      potential recruitment rates in a pilot study preliminary to a phase III
      randomized trial of decompressive craniectomy surgery in patients with diffuse
      traumatic brain injury (TBI) and refractory intracranial hypertension. MATERIALS
      AND METHODS: A study protocol was developed, inclusion and exclusion criteria
      were defined, and a standardized surgical technique was established. Neurologic
      outcomes were assessed 6 months after injury with a validated structured
      questionnaire and a single trained assessor blind to treatment group. RESULTS:
      During the 8-month pilot study at a level 1 trauma center in Melbourne,
      Australia, 69 intensive care patients with severe TBI were assessed for
      inclusion. Six patients were eligible, and 5 (8%) were randomized. Six months
      after injury, 100% of patients received outcome assessments. Key improvements to
      the multicenter Decompressive Craniectomy study protocol were enabled by the
      pilot study. CONCLUSIONS: In patients with severe TBI and refractory intracranial
      hypertension, the frequency of favorable neurologic outcomes (independent living)
      was low and similar to predicted values (40% favorable). A future multicenter
      phase III trial involving 18 neurotrauma centers with most sites conservatively
      recruiting at just 25% of the pilot study rate would require at least 5 years to
      achieve an estimated 210-patient sample size. Collaboration with neurotrauma
      centers in countries other than Australia and New Zealand would be required for
      such a phase III trial to be successful.

PMID- 18725046
TI  - Safety of percutaneous dilational tracheostomy in hematopoietic stem cell
      transplantation recipients requiring long-term mechanical ventilation.
AB  - PURPOSE: Recent reports have shown that the outcome of mechanically ventilated
      patients after hematopoietic stem cell transplantation (HSCT) has improved. This
      study was conducted to clarify if percutaneous dilational tracheostomy is safe in
      this group of patients and to report the outcome of HSCT recipients requiring
      long-term mechanical ventilation. METHODS: A retrospective review of our 8-year
      experience with patients with acute respiratory insufficiency after HSCT,
      requiring long-term mechanical ventilation and percutaneous dilational
      tracheostomy and an analysis of patient outcomes were made. RESULTS: Percutaneous
      dilational tracheostomy was safely performed in all 51 patients. Although 1
      patient (2%) developed a pneumothorax that required drainage, stoma infections or
      severe bleeding complications were not observed. Of the 51 patients in the study,
      14 (27%) survived the intensive care unit stay, and 10 of them were ventilated
      for more than 20 days. The intensive care unit survival rate for the period from
      1998 to 2001 was 11% compared with 38% for the period from 2002 to 2005 (P =
      .053). CONCLUSIONS: Percutaneous dilational tracheostomy can be safely performed
      on patients with acute respiratory failure after HSCT. This procedure did not
      result in postoperative wound infections or significant bleeding complications.
      Furthermore, the results of our study indicate that today even patients with
      prolonged mechanical ventilation (>20 days) have a chance of long-term survival.

PMID- 18725047
TI  - Reduced heart rate multiscale entropy predicts death in critical illness: a study
      of physiologic complexity in 285 trauma patients.
AB  - PURPOSE: We have shown previously that reduced integer heart rate variability
      (HRVi) predicts death in trauma patients. We hypothesized that heart rate
      multiscale entropy (MSE), a potential measurement of physiologic complexity,
      would predict death more robustly than HRVi. MATERIALS AND METHODS: Two hundred
      eighty-five patients had heart rate data meeting completeness and density
      criteria (>12 hours, >/=0.4 Hz) available in the first 24 hours after admission.
      Missing data points were interpolated, and a publicly available algorithm (MSE of
      Costa et al; Phys Rev E Stat Nonlin Soft Matter Phys. 2005;71[2 Pt 1]) was
      applied (www.physionet.org, m = 2, r = 0.15). Integer heart rate variability was
      computed using methods described previously (percentage of 5-minute intervals
      having heart rate SD between 0.3 and 0.6). Sample entropy was compared between
      survivors and nonsurvivors at each scale factor using Wilcoxon rank sum test.
      Logistic regression was used to assess risk of death based on HRVi, MSE, and/or
      covariates (age, sex, injury severity). RESULTS: Decreased HRVi and MSE each
      predicted hospital mortality (median day of death, 3; mean, 7.1). Multiscale
      entropy-based risk stratification (area under the receiver operating
      characteristic curve [AUC] = 0.76, scale 15) was superior to HRVi (AUC = 0.70),
      but this difference in AUC was not statistically significant. Multiscale entropy
      stratified patients by mortality at every scale factor (P < .001). CONCLUSIONS:
      Multiscale entropy and HRVi measured within the first 24 hours each identify
      trauma patients at increased risk of subsequent hospital death.

PMID- 18725048
TI  - Heat shock factor 1 inhibits nuclear factor-kappaB nuclear binding activity
      during endotoxin tolerance and heat shock.
AB  - RATIONALE: Sepsis, endotoxin tolerance, and heat shock (HS) all display down
      regulation of innate immunity. We hypothesize that HS factor 1 (HSF-1) induces
      competitive inhibition of nuclear factor-kappaB (NF-kappaB)-induced signal
      transduction in both endotoxin tolerance and HS. OBJECTIVES: We compared
      endotoxin tolerance and HS in RAW 264.7 cells. We transfected cells with an HS
      protein 70 (HSP70) plasmid to test whether HSP70 is the mediator of HS-induced NF
      kappaB inhibition. We studied the effects of endotoxin stimulation and HS, both
      separately and together, on "wild-type" cells, cells transfected with the HSP70
      plasmid, and cells transfected with vehicle. FINDINGS: Heat shock protein 70
      plasmid-transfected cells had increased HSP70 expression and demonstrated
      decreased nitric oxide (NO) release and inducible NO synthase messenger RNA
      expression in response to endotoxin compared with wild-type and empty plasmid
      transfected cells. Heat shock completely abolished subsequent NO and inducible NO
      synthase messenger RNA expression in wild-type cells. Heat shock factor 1 reached
      maximum expression 60 to 90 minutes after HS. Heat shock protein 70-transfected
      cells still displayed endotoxin-induced NF-kappaB nuclear binding, whereas
      endotoxin tolerance, HS, and exposure to HSF-1, but not exposure to an unrelated
      promoter, inhibited NF-kappaB nuclear binding. CONCLUSIONS: Endotoxin tolerance
      and HS appear to share a common immune suppressive effect, possibly through HSF-1
      mediated competitive inhibition of NF-kappaB nuclear binding.

PMID- 18725049
TI  - Histamine 2 receptor antagonists vs intravenous proton pump inhibitors in a
      pediatric intensive care unit: a comparison of gastric pH.
AB  - PURPOSE: The aim of this study was to assess gastric pH in critically ill
      pediatric patients receiving intravenous stress ulcer medication. MATERIALS AND
      METHODS: A prospective study was done in 48 patients with a gastric tube in place
      who were receiving either ranitidine or a proton pump inhibitor and no enteral
      nutrition. Daily peak and trough gastric pHs were measured. RESULTS: The median
      age was 7 years 5 months (range, 1 month to 19 years), the median weight was 31
      kg (range, 3-130 kg), and the median pediatric risk of mortality 2 (PRISM2) score
      was 12.5 (range, 0-31). All patients were intubated and 8 received dialysis. The
      average trough pH was 4.4 +/- 1.6 in the ranitidine group, 4.9 +/- 1.8 in the
      once daily proton pump inhibitor group, and 5.0 +/- 1.2 in the twice daily proton
      pump inhibitor group (P = .16). The average peak pH was 5.3 +/- 1.8 in the
      ranitidine group, 5.9 +/- 1.6 in the once daily proton pump inhibitor group, and
      6.0 +/- 1.0 in the twice daily proton pump inhibitor group (P = .06). Three (10%)
      of 28 trough pH measurements in the twice daily proton pump inhibitor group were
      more acidic than 4 vs 24 (40%) of 60 in the ranitidine group, and 22 (40%) of 56
      in the once daily proton pump inhibitor group (P = .02). One (4%) of 27 peak pH
      measurements in the twice daily proton pump inhibitor group were more acidic than
      4 vs 13 (20%) of 61 in the ranitidine group, and 9 (16%) of 56 in the once daily
      proton pump inhibitor group (P = .12). Three patients (6%; 95% confidence
      interval, 0.51%-16%) developed upper gastrointestinal bleeding, and 4 patients
      (8%; 95% confidence interval, 0%-13%) developed ventilator-acquired pneumonia.
      CONCLUSIONS: Many critically ill pediatric patients receiving stress ulcer
      prophylaxis have a trough or peak gastric pH more acidic than 4.

PMID- 18725050
TI  - Ciprofloxacin pharmacokinetics in critically ill patients: a prospective cohort
      study.
AB  - PURPOSE: Optimal dosing of antibiotics is important for efficacy and avoidance of
      resistance. Fluoroquinolones are frequently used to treat severe infections in
      critically ill patients. We studied ciprofloxacin pharmacokinetics after
      administration of 400 mg twice a day (bid) intravenously (IV). MATERIAL AND
      METHODS: Serum concentrations were measured in 32 intensive care unit patients
      (age, 68.7 +/- 17.4 years; Sepsis-related Organ Failure Assessment (SOFA) scores,
      7.3 +/- 3.4). Blood samples were drawn at 7 time points after ciprofloxacin
      infusion. We evaluated whether areas under the curve (AUCs) exceeded minimal
      inhibitory concentration (MIC) values of 0.125, 0.25, 0.5, 1.0, and 2.0 mg/L by
      125 times and peak concentrations (C(max)) 10 x MIC (C(max)/MIC >10). RESULTS:
      The AUC/MIC more than 125 was achieved in 100% for MIC 0.125. For MIC values
      0.25, 0.5, 1.0, and 2.0, results were 84%, 31%, 3%, and 0%, respectively (P <
      .01). The C(max)/MIC more than 10 for MIC values of 0.125, 0.25, 0.5, 1.0, and
      2.0 was realized in 100%, 97%, 69%, 25%, and 0%, respectively (P < .01). Female
      sex, SOFA(pulmonary) points, and SOFA(renal) points predicted higher AUC.
      Cumulative SOFA scores were most predictive of high AUCs. CONCLUSIONS:
      Ciprofloxacin 400 mg bid IV leads to inadequate AUC/MIC and C(max)/MIC ratios in
      many cases. Effective killing concentrations were only achieved in pathogens with
      MIC less than 0.25. As bacteria in intensive care unit patients often exceed this
      threshold, we recommend to use higher doses of ciprofloxacin (1200 mg daily) to
      ensure optimal bacterial killing and avoid antibiotic resistance.

PMID- 18725051
TI  - A case of severe hyperkalemia: fast, safe and effective treatment is required.

PMID- 18725052
TI  - Health effects of soda drinking in adolescent girls in the United Arab Emirates.
AB  - BACKGROUND: There is a growing concern in the medical and scientific communities
      about the harmful effects associated with carbonated soft drinks. In several
      observational studies, intake of carbonated beverages was associated with reduced
      bone mass, decreased calcium level in the blood, and increased fracture risk.
      Soda drinks is a contributing factor in the prevalence and incidence of both
      dental caries and obesity especially among adolescents and young adults so they
      are more likely to be diagnosed as diabetic. OBJECTIVES: This study aims at
      studying the prevalence of soda drinking among adolescent girls and discovering
      its health effects. SUBJECTS AND METHODS: A cross-sectional study was designed,
      and a multistage random sample was performed in schools and colleges in Dubai. A
      total of 275 students were selected. A self-administrative questionnaire was
      distributed and blood, and urine samples were collected. Anthropometric measures
      and laboratory investigations (lipid profile, renal function, and blood and urine
      electrolytes) were done. RESULTS: Age range was 10 to 22 years, with mean of 16.2
      years. Prevalence of soda drinking was 81.8%. About half of the ever-drinkers
      (47.5%) have tried to quit drinking. There was no significant difference in body
      mass index between drinkers and nondrinkers (chi(2) = 2.1, P > .05). The
      concentration of blood sodium was less in drinkers, whereas the concentrations of
      urea and creatinine were not affected by drinking. There was no significant
      difference in blood calcium between drinkers and non drinkers (P > .05). Drinkers
      were associated with higher risk of increased calcium and phosphorus excretion in
      urine (odds ratio, 1.1; 95% confidence interval, 0.38-3.3). CONCLUSION: Soda
      drinking was associated with higher risk of obesity and decreasing level of blood
      calcium and increasing urinary calcium excretion, which may lead to osteoporosis
      later in life. Soda drinking did not have any effect on renal function tests in
      our study group.

PMID- 18725053
TI  - Microsatellite polymorphism of the human leptin gene and risk of obesity.
AB  - BACKGROUND: Leptin is a hormone mainly produced by adipose tissue. It acts on
      both energy intake and expenditure to maintain relative stability of body weight
      and energy storage over long period of time. Variation in size of the
      tetranucleotide repeat located at the 3' end of leptin gene (LEP3'HVR) can
      influence leptin expression. OBJECTIVES: To predict the association of LEP3'HVR
      and obesity. MATERIALS AND METHODS: A case control study consisting of 40
      individuals with normal BMI (control group) and 35 individuals with abnormal BMI.
      LEP3'HVR polymorphic region was amplified by polymerase chain reaction, and
      fragments were analyzed by agarose gel electrophoresis. Statistical analysis was
      done using SPSS (SPSS, Chicago, Ill). RESULTS: The frequency of LEP3'HVR class I
      was 52.8% in individuals with abnormal BMI versus 42.5% in the individuals with
      normal BMI. The homozygous class I (I/I) genotype was identified in 40% of the
      individuals with abnormal BMI vs 25% of the control group. Individuals with I/I
      genotypes showed a higher prevalence of obesity when compared with homozygous
      class II/II genotype (odds ratio, 1.9; 95% confidence interval, 0.6-5.6).
      CONCLUSION: Class (I/I) genotype of LEP3'HVR was associated with increase risk of
      obesity.

PMID- 18725054
TI  - Polymorphism of glutathione S-transferases as genetic risk factors for the
      development of complications in type 2 diabetes mellitus.
AB  - BACKGROUND: Diabetes is characterized by chronic hyperglycemia that produces
      dysregulation of cellular metabolism and result in excess free radical production
      and oxidative stress. Glutathione S-transferases (GSTs) are a family of
      multifunctional enzymes that work as antioxidants. Therefore, diminished
      expression of GSTs may result in a reduced body defense against oxidative stress,
      followed by development of diabetic complications. OBJECTIVES: To investigate the
      possible association between GSTM1 and GSTT1 polymorphism and the occurrence of
      complications in type 2 DM and to study the other risk factors for complications
      in DM. METHODS: Twenty noncomplicated type 2 diabetic patients and 40 complicated
      type 2 diabetic patients were enrolled in the study. The GSTM1 and GSTT1
      genotypes were identified by polymerase chain reaction of peripheral blood DNA
      samples. Analysis of data was done by using SPSS (SPSS, Chicago, Ill). RESULTS:
      The frequencies of null GSTM1 and GSTT1 genotypes were 55% (11/20) and 40%
      (8/20), respectively, in noncomplicated DM group. The frequencies of null GSTM1
      and GSTT1 genotype in complicated DM group were 57.5% (23/40) and 60% (24/40),
      respectively. The null GSTT1 genotype was more prevalent in the group of
      complicated DM with odds ratio (odds ratio, 2.3; 95% confidence interval, 0.75
      6.7) when compared with noncomplicated DM. CONCLUSION: Our data provide evidence
      that diabetics with null GSTT1 genotypes are substantially at higher risk for
      developing complications.

PMID- 18725058
TI  - A review of special education law.
AB  - Children with disabilities require special education and related services that
      are as diverse as the individual children themselves. Special education is not
      necessarily a special classroom but a well thought-out program of collaborative
      interventions leading to educational goals set forth by a multidisciplinary team.
      Effective special education is guided by both state and federal laws that protect
      the rights of the child and encourage certain universal core principles. Special
      needs children are entitled to a free and appropriate education with related
      services in the least restrictive environment. Pediatricians and pediatric
      subspecialists are in a unique position to develop a medical home for the
      disabled child, and in doing so must be well-versed in both case law and federal
      legislation as it applies to special education, in an effort to be a child's best
      advocate. A chronological review of case law and federal legislation, including
      the Individuals with Disabilities Education Act, No Child Left Behind Act, and
      recent amendments, are discussed, and their relevance to physician practice is
      detailed.

PMID- 18725059
TI  - Neonatal sinovenous thrombosis: presentation and association with imaging.
AB  - Few studies have examined when children with neonatal sinovenous thrombosis come
      to medical attention, risk factors associated with time of presentation, what
      clinical presentations are more likely to occur early or late, or whether the
      timing of presentation or severity of clinical presentation correlate with
      radiographic findings. Chi-square and Fisher's exact tests were used to explore
      associations in a cohort of 59 neonates with sinovenous thrombosis. Most (66%)
      came to medical attention within 48 hours of birth (defined as early
      presentation). Most (88%) had multiple comorbidities. Respiratory distress (P =
      0.005), hypoxia (P = 0.02), poor tone (P = 0.05), fetal distress (P < 0.001),
      preterm delivery (P = 0.044), and low Apgar score (P = 0.018) were associated
      with early presentation. Infant dehydration was associated with late presentation
      (P < 0.001). Time of presentation was not associated with radiographic severity.
      Presentation with difficult-to-control seizures was marginally associated with
      hemorrhage (P = 0.096) but no other measure of radiographic severity. Neonates
      with sinovenous thrombosis often present within 48 hours, with multiple
      comorbidities and presenting signs, some of which are associated with time of
      presentation. Neither timing of presentation nor presence or absence of severe
      seizures can be used to predict findings on radiographic imaging.

PMID- 18725060
TI  - Rapid eye movement latency in children and adolescents.
AB  - Rapid eye movement sleep distribution changes during development, but little is
      known about rapid eye movement latency variation in childhood by age, sex, or
      pathologic sleep states. We hypothesized that: (1) rapid eye movement latency
      would differ in normal children by age, with a younger cohort (1-10 years)
      demonstrating shorter rapid eye movement latency than an older group (>10-18
      years); (2) rapid eye movement latency in children would differ from typical
      adult rapid eye movement latency; and (3) intrinsic sleep disorders (narcolepsy,
      pediatric obstructive sleep apnea syndrome) would disrupt normal developmental
      patterns of rapid eye movement latency. A retrospective chart review included
      data from clinic visits and of rapid eye movement latency and other parameters
      measured by overnight polysomnography. Participants included 98 control children,
      90 children with obstructive sleep apnea syndrome, and 13 children with
      narcolepsy. There were no statistically significant main effects of age category
      or sex on rapid eye movement latency. Rapid eye movement latency, however,
      exhibited a significant inverse correlation with age within the older control
      children. Healthy children exhibited rapid eye movement latencies significantly
      longer than adults. Normal control patients demonstrated significantly longer
      rapid eye movement latency than obstructive sleep apnea syndrome and narcolepsy
      patients.

PMID- 18725061
TI  - Spectrum of polysomnographic abnormalities in children with epilepsy.
AB  - This study sought to evaluate polysomnographic abnormalities in a cohort of 40
      children with epilepsy who underwent a sleep study because of various sleep
      complaints. Retrospective analyses included polysomnographic variables,
      antiepileptic drugs, type of epilepsy, and seizure control. The subgroup with
      epilepsy and obstructive sleep apnea syndrome was compared with 11 children who
      manifested uncomplicated obstructive sleep apnea syndrome. Thirty-three patients
      (83%) exhibited snoring (42.5%), sleep-disordered breathing (obstructive
      hypoventilation, 12.5%; obstructive sleep apnea, 20%; and upper-airway resistance
      syndrome, 7.5%), or periodic limb movements of sleep (10%). Children with poor
      seizure control demonstrated significantly lower sleep efficiency, a higher
      arousal index, and a higher percentage of rapid-eye-movement sleep compared with
      children who were seizure-free or exhibited good seizure control. Patients with
      epilepsy and obstructive sleep apnea had significantly a higher body mass index,
      longer sleep latency, a higher arousal index, and a lower apnea-hypopnea index,
      but significantly more severe desaturation compared with patients with
      uncomplicated obstructive sleep apnea. A significant proportion of children with
      epilepsy referred for polysomnography with diverse sleep problems manifest sleep
      disordered breathing, including obstructive sleep apnea syndrome.

PMID- 18725062
TI  - Lack of valproic acid-associated weight gain in prepubertal children.
AB  - We evaluated whether prepubertal children treated with valproic acid did not gain
      excessive weight. This retrospective study of children with epilepsy, aged <12
      years at enrollment, examined weight gain associated with valproic acid or
      carbamazepine monotherapy. There was no significant difference between the
      valproic acid (n = 31) and carbamazepine (n = 49) treated groups in average
      duration of therapy or mean age. Body mass index scores at the beginning and end
      of the study were used to evaluate weight gain, while compensating for gains in
      height. For valproic acid, the linear mixed model detected no gain in body mass
      index z-scores over time (T = 0.25, DF = 17.3, P = 0.80), though it detected a
      significant gain in body mass index z-scores for carbamazepine (T = 2.32, DF =
      36.7, P = 0.02). Results for McNemar chi-square tests were similar. No
      significant proportion change occurred among children on valproic acid (chi(2) =
      2.0, P = 0.15), whereas a significant increase in the proportion of overweight
      children occurred on carbamazepine (chi(2) = 4.5, P = 0.03). We detected no
      excessive weight gain for children on valproic acid, whereas this was
      demonstrated for a similar socioeconomic group on carbamazepine.

PMID- 18725063
TI  - Alpha-methyl-l-tryptophan positron emission tomography in epilepsy with cortical
      developmental malformations.
AB  - Preliminary studies suggest that alpha[(11)C]methyl-l-tryptophan positron
      emission tomography can detect the epileptic focus within malformations of
      cortical development. We determined the sensitivity and specificity of alpha
      [(11)C]methyl-l-tryptophan positron emission tomography in identifying epileptic
      focus in children with intractable, neocortical epilepsy with and without
      malformations of cortical development. Seventy-three epileptic children were
      classified into lesional and nonlesional groups, and compared regarding focal
      increased alpha-[(11)C]methyl-l-tryptophan uptake. The sensitivity and
      specificity of focal increased alpha-[(11)C]methyl-l-tryptophan uptake, using
      intracranial electroencephalogram localization of seizure onset as the standard,
      were compared between lesional and nonlesional groups. The specificity of alpha
      [(11)C]methyl-l-tryptophan positron emission tomography for detecting seizure
      onset lobe was equally high in lesional (97%) and nonlesional groups (100%),
      whereas sensitivity was higher in the lesional than the nonlesional group (47%
      versus 29%; P = 0.047). The incidence of alpha-[(11)C]methyl-l-tryptophan uptake
      abnormality was higher in the lesional than the nonlesional group (P < 0.01).
      Alpha-[(11)C]methyl-l-tryptophan positron emission tomography localized and
      visualized epileptogenic regions in 25% of patients with nonlocalizing magnetic
      resonance imaging. Although overall sensitivity of alpha-[(11)C]methyl-l
      tryptophan positron emission tomography in identifying neocortical epileptic
      focus is modest, specificity is extremely high. When an alpha-[(11)C]methyl-l
      tryptophan focus is detected, it likely represents the epileptogenic region to be
      resected.

PMID- 18725064
TI  - Brainstem auditory outcomes and correlation with neurodevelopment after perinatal
      asphyxia.
AB  - We used brainstem auditory-evoked responses and neurodevelopmental assessment to
      detect abnormalities and correlations between such responses and
      neurodevelopmental outcomes in 78 children (aged 4-12 years) who survived
      perinatal asphyxia. Twenty children had brainstem auditory-evoked response
      abnormalities, including increased threshold, reduced wave V amplitude, decreased
      V/I amplitude ratio, and prolonged I-V interval. Thirty-seven exhibited
      neurodevelopmental deficits, including cerebral palsy and developmental delay.
      The remaining 41 exhibited no deficits. Brainstem auditory-evoked response
      abnormalities were evident in 15 of 37 (40.5%) children with neurodevelopmental
      deficits, but in only 5 of 41 (12.2%) with no deficits, which differed
      significantly (chi(2) = 8.2, P < 0.05). The sensitivity, specificity, positive
      predictive value, and false-negative rate of brainstem auditory-evoked responses
      to reflect neurodevelopmental outcomes were 40.5%, 87.8%, 75.0%, and 59.5%,
      respectively. These findings suggest that in children who survive perinatal
      asphyxia, brainstem auditory impairment occurs more frequently in those with
      versus those without neurodevelopmental deficits. Brainstem auditory-evoked
      responses display a moderate correlation with clinically determined
      neurodevelopmental outcomes. Despite limitations, brainstem auditory-evoked
      response is valuable for assessing auditory and neurodevelopmental outcomes after
      perinatal asphyxia.

PMID- 18725065
TI  - Neurocardiogenic syncope complicating pediatric transcranial magnetic
      stimulation.
AB  - Pediatric applications of transcranial magnetic stimulation are rapidly
      expanding, but lack the safety data established for adults. Transcranial magnetic
      stimulation-induced neurocardiogenic syncope may represent an age-dependent
      adverse event that is essentially undescribed in the transcranial magnetic
      stimulation literature. We report on 2 adolescents (of 10 children studied) with
      transcranial magnetic stimulation-related neurocardiogenic syncope, identify
      modifiable risk factors, and suggest measures to improve the safety of future
      pediatric transcranial magnetic stimulation studies.

PMID- 18725066
TI  - Reye syndrome and reye-like syndrome.
AB  - Reye syndrome is an acute metabolic encephalopathy, largely affecting children
      and adolescents. In Reye-like syndrome, because of inborn errors of metabolism,
      hypoglycemia, hypoketonemia, elevated ammonia, and organic aciduria are often
      evident. It is well-known that fatty-acid oxidation defects can present as Reye
      like syndrome. The most commonly diagnosed metabolic disorder in association with
      Reye syndrome has been medium-chain acyl coenzyme A dehydrogenase deficiency. The
      present consensus seems to be that Reye syndrome is very rare, and that any child
      suspected of manifesting this disorder should undergo investigations for inborn
      errors of metabolism. We recently treated a child with "Reye-like illness" who
      possibly manifested a long-chain acyl dehydrogenase deficiency, and who had also
      ingested aspirin. We discuss the possible pathogenesis of the disorder in this
      child. The end results of mitochondrial dysfunction in Reye syndrome and Reye
      like illness may be similar.

PMID- 18725067
TI  - Craniectomy in herpetic encephalitis.
AB  - The morbidity and mortality of herpes simplex encephalitis have decreased since
      the 1980s with the use of antivirals, but have remained stable in the last couple
      of years. One cause of morbidity is the development of focal hemorrhagic necrosis
      and edema in the temporal lobe, giving rise to space-occupying lesions, with a
      subsequent elevation of intracranial pressure. In some cases, the necrosis and
      edema can be refractory to medical treatment, with fatal outcome. Under these
      circumstances, some authors proposed decompressive craniectomy to treat severe
      intracranial hypertension and prevent serious neurologic deficits. We report the
      clinical outcomes of 2 adolescents affected with herpes simplex encephalitis who
      developed, during the course of their illness, severe intracranial hypertension
      refractory to medical treatment. Decompressive surgery was undertaken, with good
      outcomes in both patients.

PMID- 18725068
TI  - Infant botulism type Ba: first culture-confirmed case in the United Arab
      Emirates.
AB  - We report on a 3-month-old girl with culture-confirmed infant botulism caused by
      a rare double toxin-producing Clostridium botulinum type Ba. This case was not
      related to honey-feeding. The clinical course was prolonged, with minimal
      spontaneous improvement at onset, and a period of fluctuating motor weakness and
      nasogastric feeding dependence afterward. Neurophysiologic studies produced
      normal results. Human botulism immune globulin was administered empirically on
      day 23 of presentation, with rapid full recovery. This case highlights the
      importance of pursuing diagnoses of infant botulism despite normal results of
      neurophysiologic testing and no history of honey-feeding. Our case also
      demonstrates a favorable response to human botulism immune globulin, despite the
      relatively late treatment.

PMID- 18725069
TI  - Sleep-disordered breathing in Chiari malformation type 1.
AB  - Type 1 Chiari malformation is defined as an elongation of the cerebellar tonsils
      >6 mm below the foramen magnum. Central sleep apnea is a well-recognized sign,
      and can be an initial presentation, of this malformation. Obstructive sleep apnea
      is not a widely recognized sign of Chiari type 1 malformation, though there were
      a few case reports. We present a 13-year-old girl who presented at our
      respiratory clinic with excessive nighttime snoring. Magnetic resonance imaging
      revealed a Chiari type 1 malformation requiring decompression. We emphasize the
      importance of including cervicomedullary junction disorders in the differential
      diagnosis of apnea, and we review the literature concerning mixed apneas and
      obstructive sleep apneas in Chiari type 1 malformation.

PMID- 18725070
TI  - Neuromyelitis optica in a young child with positive serum autoantibody.
AB  - Relapsing neuromyelitis optica is rare in children. The identification of a
      highly specific serum autoantibody marker (neuromyelitis optica-immunoglobulin G)
      differentiates neuromyelitis optica from other demyelinating disorders,
      particularly in clinically challenging cases. We present a child with multiple
      episodes of transverse myelitis and optic neuritis with positive neuromyelitis
      optica-immunoglobulin G titers, consistent with a diagnosis of relapsing
      neuromyelitis optica. Serial titers of neuromyelitis optica-immunoglobulin G
      normalized during remission.

PMID- 18725071
TI  - Rituximab and intravenous immunoglobulins for relapsing postinfectious opsoclonus
      myoclonus syndrome.
AB  - We describe 2 children with postinfectious opsoclonus-myoclonus syndrome.
      Although the patients initially responded to monotherapy with methylprednisolone,
      intravenous immunoglobulins, or rituximab, they manifested persistent neurologic
      deficits and relapsing signs. Treatment with rituximab in combination with
      intravenous immunoglobulin, however, resulted in significant longterm clinical
      improvement.

PMID- 18725072
TI  - Vertebral artery dissection in a patient with Wildervanck syndrome.
AB  - Vertebral artery dissection as a cause of stroke is rarely reported in children.
      The association between vertebral artery dissection and Klippel-Feil syndrome is
      also very rare. We report on a case of vertebral artery dissection with posterior
      circulation involvement in a child with Klippel-Feil syndrome after a hard
      physical-training lesson. She was also diagnosed with Wildervanck syndrome, with
      additional clinical findings. Vertebral artery dissection should be considered in
      patients with Klippel-Feil syndrome who present with acute-onset neurologic
      signs. Movements such as hyperextension with rotation of the neck should be
      avoided in these cases.

PMID- 18725073
TI  - High-dose midazolam in convulsive status epilepticus.

PMID- 18725074
TI  - Proceedings of the 9th NPY International Meeting, March 16-20, 2008, Okinawa,
      Japan.

PMID- 18725075
TI  - Role of hypothalamic AMP-kinase in food intake regulation.
AB  - Adenosine monophosphate-activated protein kinase (AMPK) functions as a cellular
      fuel gauge that regulates metabolic pathways in nutrient metabolism. Recent
      studies have strongly implicated that AMPK in the hypothalamus regulates energy
      metabolism by integrating inputs from multiple hormones, peptides,
      neurotransmitters, and nutrients. Leptin is an adipocyte hormone that regulates
      food intake and energy expenditure in peripheral tissues. Leptin inhibits AMPK
      activity in the arcuate and paraventricular hypothalamus, and its inhibition is
      necessary for the anorexic effect of leptin. Alteration of hypothalamic AMPK
      activity is sufficient to change food intake and body weight. Furthermore,
      fasting/refeeding, glucose, and melanocortin receptor alter AMPK activity in the
      hypothalamus. Adiponectin has also been shown to increase food intake by
      activating AMPK in the arcuate hypothalamus. Recent data have shown that acetyl
      coenzyme A carboxylase/malonyl-coenzyme A/carnitine palmitoyltransferase-1/fatty
      acid oxidation and mammalian target of rapamycin signalings are putative
      downstream pathways for food intake regulation in response to hypothalamic AMPK.
      Thus, these results suggest that food intake and nutrient metabolism are
      coordinately regulated by the common signaling pathway of AMPK in the
      hypothalamus.

PMID- 18725076
TI  - Emergence of ghrelin as a treatment for cachexia syndromes.
AB  - Cachexia is a constellation of symptoms that amount to body wasting in the
      setting of a variety of chronic illnesses, including cancer, heart failure,
      chronic kidney disease, and acquired immunodeficiency syndrome. Cachexia is
      particularly worrisome clinically because it is associated with a worsened
      prognosis of the underlying disease. Despite a large amount of study in this
      area, no single agent has been shown to have consistent efficacy in human trials.
      One promising class in this setting is ghrelin receptor agonists. Ghrelin binds
      to the growth hormone secretagogue-1a receptor in appetite-regulating centers in
      the brain, increasing expression of neuropeptide Y and agouti-related peptide
      during short-term treatment. Ghrelin has also been shown to have anti
      inflammatory properties, which is significant, given that cachexia is thought to
      be produced at least partly by inflammation induced by the underlying disease.
      Animal studies have demonstrated efficacy using growth hormone secretagogue
      receptor agonists to treat cachexia caused by cancer, chemotherapy, and chronic
      kidney disease. Limited human trials using ghrelin or ghrelin receptor agonists
      in cancer and heart disease have shown improved appetite and body mass during
      treatment, although longer-term trials are needed to confirm sustained effects.
      Also uncertain--but an intriguing possibility--is whether the improved weight
      gain with ghrelin treatment might also lessen the severity of the underlying
      disease and improve outcomes.

PMID- 18725077
TI  - Cachexia and neuropeptide Y.
AB  - Cachexia or wasting disease occurs commonly in diseases that have an
      overproduction of proinflammatory cytokines associated with them. The hallmarks
      of cachexia are loss of lean and adipose tissue, anorexia, anemia, memory
      disturbance, and sickness behavior. This review suggests that increased inducible
      nitric oxide synthase production in the hypothalamus leads to severe anorexia and
      that this is the pathway through which proinflammatory cytokines produce
      anorexia. Orexigenic peptides, such as neuropeptide, ghrelin, and orexin A, and
      anorectic peptides, such as leptin, produce their effects through neuronal nitric
      oxide synthase. Activation of neuronal nitric oxide synthase results in increased
      adenosine monophosphate kinase and a decrease in malonyl coenzyme A, leading to
      increased food intake.

PMID- 18725079
TI  - Hypothalamic neuronal histamine regulates body weight through the modulation of
      diurnal feeding rhythm.
AB  - Hypothalamic neuronal histamine and its H(1) receptor (H(1)-R), a leptin
      signaling pathway in the brain, regulate body weight and adiposity by affecting
      food intake and energy expenditure. Glucagon-like peptide-1 and/or corticotrophin
      releasing hormone mediate leptin signaling to neuronal histamine. Leptin-induced
      suppression of food intake and upregulation of uncoupling protein-1 expression in
      brown adipose tissue were partially attenuated in histamine H(1)-R knockout
      (H(1)KO) mice. H(1)KO mice developed maturity-onset obesity. Hyperphagia and
      decreased energy expenditure assessed by the expression of uncoupling protein-1
      mRNA were observed in older (48-wk-old) obese H(1)KO mice but not in younger (12
      wk-old) non-obese H(1)KO mice. However, the diurnal feeding rhythm was impaired
      even in younger non-obese animals. Specifically, disruption of the feeding rhythm
      developed before the onset of obesity in H(1)KO mice. Correction of these
      abnormal feeding rhythms with scheduled feeding improved the obesity and
      associated metabolic disorders in the H(1)KO mice. These findings suggest that
      histamine H(1)-R is crucial for regulating the feeding rhythm and in mediating
      the effects of leptin. Early disruption of H(1)-R-mediated functions in H(1)KO
      mice may lead to hyperphagia and decreased energy expenditure, which may
      contribute to the development of obesity in these animals.

PMID- 18725078
TI  - Disruption in the leptin-NPY link underlies the pandemic of diabetes and
      metabolic syndrome: new therapeutic approaches.
AB  - Multidisciplinary research from my and my colleagues' laboratory has shown that
      disruption at various levels of leptin signaling to the interactive hypothalamic
      network of neuropeptide Y (NPY) and cohorts contributes to the antecedent
      pathophysiologic sequelae of the disease cluster of the metabolic syndrome.
      Disruptions in NPY signaling due to high or low abundance of NPY and cognate
      receptors dysregulate the homeostatic milieu to promote hyperinsulinemia,
      hyperglycemia, fat accrual, and overt diabetes. Hyperleptinemia induced by
      consumption of energy-rich diets inhibits leptin transport across the blood-brain
      barrier and thereby produces leptin insufficiency in the hypothalamus. Sustained
      leptin insufficiency results in loss of hypothalamic restraint on pancreatic
      insulin secretion and diminished glucose metabolism and energy expenditure. This
      chain of events culminates in hyperinsulinemia, hyperglycemia, and diabetes. Our
      recent studies have shown that increasing the supply of leptin centrally by gene
      therapy reinstates the restraint on hypothalamic NPY signaling and ameliorates
      diabetes and the attendant disease cluster of the metabolic syndrome. Thus, newer
      therapies that would enhance leptin transport across the blood-brain barrier in a
      timely manner or reinstate leptin restraint on NPY signaling through central
      leptin gene therapy or pharmacologically with leptin mimetics are likely to
      curtail the pathophysiologic sequelae of diabetes and related ailments of the
      metabolic syndrome.

PMID- 18725080
TI  - Weight regain after Roux-en-Y: a significant 20% complication related to PYY.
AB  - OBJECTIVE: Roux-en-Y gastric bypass (RYGB) produces rapid and dramatic weight
      loss in very heavy obese patients. Up to 20% cannot sustain their weight loss
      beyond 2 to 3 y after surgery. METHODS: To identify putative etiologic factors
      producing post-RYGB weight regain, a literature survey of metabolic changes in
      very obese and a review of our diet-induced obese RYGB rat model data was done.
      RESULTS: Weight regain suggests an imbalance in physiologic mechanisms regulating
      appetite and metabolic rate. Weight regain occurred in 25% of our rats, produced
      by return to presurgical energy intake levels. The 75% of rats that sustained
      weight loss secreted a significantly larger amount of peptide YY (PYY) while
      suppressing leptin secretion; those that failed were unable to develop or sustain
      a sufficiently large plasma PYY:leptin ratio. Metabolic consequences of this
      failure included reversal of initial postsurgical increases in peripheral fatty
      acid oxidation, anorexigenic activity in the hypothalamic arcuate nucleus and
      paraventricular nucleus, and the expression of uncoupling protein-2 in adipose
      tissues, and decreases in hepatic lipogenesis, free tri-iodothyronine secretion,
      expression of orexigenic activity in the arcuate nucleus and paraventricular
      nucleus, expression of adenosine monophosphate kinase in adipose tissues,
      skeletal muscle mitochondrial mass, and endocannabinoid content and appetite.
      CONCLUSION: Weight regain after RYGB occurs in approximately 20% of patients and
      constitutes a serious complication. Weight regain-promoting consequences are
      attributed to a failure to sustain elevated plasma PYY concentrations, indicating
      that combining RYGB with pharmacologic stimulation of PYY secretion in patients
      after RYGB who exhibit inadequate PYY concentration may increase long-term
      success of surgical weight reduction in morbidly obese adults.

PMID- 18725081
TI  - Novel functions of orexigenic hypothalamic peptides: from genes to behavior.
AB  - The regulation of energy balance depends on the precise co-ordination of multiple
      peripheral and central systems. Much recent research has highlighted the
      importance of behavioral mechanisms is this control and suggested that the
      regulation of body weight shares central nervous system pathways in common with
      other complex behaviors, including learning and drug addiction. We present a
      brief review of some of this work and highlight the novel functions for central
      orexigenic neuropeptides. We review evidence that organisms engage in critical
      regulatory behaviors before and after ingestion has occurred. Additional evidence
      supports the idea that appetitive mechanisms are engaged that are critical for
      the regulation of intake during the act of ingestion. We briefly discuss the
      recent work on the potential role for central nervous system reward centers, how
      those might be critically linked to the central regulation of food intake, and
      how they may be dysregulated by the abundance of highly palatable, energy-dense
      foods.

PMID- 18725082
TI  - Neural networks of several novel neuropeptides involved in feeding regulation.
AB  - Novel neuropeptides acting as G-protein-coupled receptor (GPCR) ligands are known
      to be localized in the brain and play a range of physiologic functions, one of
      which is feeding regulation. We describe the distribution and localization of
      these recently identified GPCR ligands and review their involvement in neuronal
      networks, particularly in feeding regulation. This review addresses aspects of
      some novel GPCR ligands, including feeding-regulating neuropeptides such as
      orexin, ghrelin, and galanin-like peptide and other known neuropeptides such as
      neuropeptide Y and pro-opiomelanocortin. These neuropeptides have been studied by
      our research group and others, particularly with regard to interactions in the
      hypothalamus of neurons containing these neuropeptides. In the hypothalamus,
      cross-talk among such neurons plays a key role in determining feeding states and
      feeding behavior. We describe some structural and functional characteristics of
      these neuropeptides and summarize the known interactions between the different
      kinds of feeding-regulating neurons and leptin-targeting neurons in the
      hypothalamus. Moreover, we present a new strategy for analyzing neural circuits
      involving these feeding-regulating GPCR ligands in the brain, with research in
      this field aided by the use of transgenic mouse models. We also present our
      recent results that involve aspects of feeding regulation, energy homeostasis,
      and body temperature regulation. Research in this field will serve the important
      role of clarifying neurologically based causes for appetite dysfunctions and
      diseases and may help in establishing new therapies for patients with such
      conditions.

PMID- 18725083
TI  - Emerging role of autoantibodies against appetite-regulating neuropeptides in
      eating disorders.
AB  - OBJECTIVE: Recent findings of autoantibodies directed against melanocortin
      peptides suggest that these autoantibodies may represent a source of variability
      in peptidergic signaling that can be responsible for altered appetite and emotion
      in eating disorders. However, it is still unknown if autoantibodies directed
      against some other appetite-regulating neuropeptides and peptide hormones exist
      in healthy human subjects and if these autoantibodies can regulate appetite and
      emotion. METHODS: We determined the presence of autoantibodies against some key
      appetite-regulating neuropeptides and peptide hormones in sera of human subjects
      and in rats, and used animal models to study the role of alpha-melanocyte
      stimulating hormone autoantibodies in food intake and anxiety. RESULTS:
      Immunoglobulin G and A autoantibodies against alpha-melanocyte-stimulating
      hormone, neuropeptide Y, agouti-related protein, ghrelin, leptin, and some other
      neuropeptides or peptide hormones involved in appetite control were present in
      healthy humans and rats. Animal models including active and passive transfer
      showed that alpha-melanocyte-stimulating hormone autoantibodies are involved in
      the regulation of feeding and anxiety. Sequence homology was found between
      neuropeptides and proteins from some members of intestinal microflora, whereas
      germ-free rats showed altered levels of autoantibodies directed against several
      neuropeptides. CONCLUSION: Autoantibodies directed against appetite-regulating
      neuropeptides and peptide hormones are emerging as important participants in the
      peptidergic mechanisms controlling motivated behavior. Furthermore, these
      autoantibodies could provide a link in the gut-brain axis and may represent new
      biological targets for the diagnosis and treatment of eating disorders.

PMID- 18725084
TI  - NPY and its involvement in axon guidance, neurogenesis, and feeding.
AB  - OBJECTIVES: The role of neuropeptides in nervous system function is still in many
      cases undefined. In the present study we examined a possible role of the 36-amino
      acid neuropeptide Y (NPY) with regard to three functions: axon guidance and
      attraction/repulsion, adult neurogenesis, and control of food intake. METHODS:
      Growth cones from embryonic dorsal root ganglion neurons were studied in culture
      during asymmetrical gradient application of NPY. Growth cones were monitored over
      a 60-min period, and final turning angle and growth rate were recorded. In the
      second part the NPY Y(1) and Y(2) receptors were studied in the subventricular
      zone, the rostral migratory stream, and the olfactory bulb in normal mice and
      mice with genetically deleted NPY Y(1) or Y(2) receptors. In the third part an
      anorectic mouse was analyzed with immunohistochemistry. RESULTS: 1) NPY elicited
      an attractive turning response and an increase in growth rate, effects exerted
      via the NPY Y(1) receptor. 2) The NPY Y(1) receptor was expressed in neuroblasts
      in the anterior rostral migratory stream. Mice deficient in the Y(1) or Y(2)
      receptor had fewer proliferating precursor cells and neuroblasts in the
      subventricular zone and rostral migratory stream and fewer neurons in the
      olfactory bulb expressing calbindin, calretinin or tyrosine hydroxylase. 3) In
      the anorectic mouse markers for microglia were strongly upregulated in the
      arcuate nucleus and in projection areas of the NPY/agouti gene-related protein
      arcuate system. CONCLUSION: NPY participates in several mechanisms involved in
      the development of the nervous system and is of importance in the control of food
      intake.

PMID- 18725085
TI  - Y1 receptor knockout increases nociception and prevents the anti-allodynic
      actions of NPY.
AB  - OBJECTIVE: Recent pharmacologic studies in our laboratory have suggested that the
      spinal neuropeptide Y (NPY) Y1 receptor contributes to pain inhibition and to the
      analgesic effects of NPY. To rule out off-target effects, the present study used
      Y1-receptor-deficient (-/-) mice to further explore the contribution of Y1
      receptors to pain modulation. METHODS AND RESULTS: Y1(-/-) mice exhibited reduced
      latency in the hotplate test of acute pain and a longer-lasting heat allodynia in
      the complete Freund's adjuvant (CFA) model of inflammatory pain. Y1 deletion did
      not change CFA-induced inflammation. Upon targeting the spinal NPY systems with
      intrathecal drug delivery, NPY reduced tactile and heat allodynia in the CFA
      model and the partial sciatic nerve ligation model of neuropathic pain.
      Importantly, we show for the first time that NPY does not exert these anti
      allodynic effects in Y1(-/-) mice. Furthermore, in nerve-injured CD1 mice,
      concomitant injection of the potent Y1 antagonist BIBO3304 prevented the anti
      allodynic actions of NPY. Neither NPY nor BIBO3304 altered performance on the
      Rotorod test, arguing against an indirect effect of motor function. CONCLUSION:
      The Y1 receptor contributes to pain inhibition and to the analgesic effects of
      NPY.

PMID- 18725086
TI  - Molecular recognition of the NPY hormone family by their receptors.
AB  - Many G-protein-coupled receptors belong to families of different receptor
      subtypes, which are recognized by a variety of distinct ligands. We summarize the
      current state of the art of the multireceptor/multiligand system of the so-called
      Y-receptor family. This family consists of four G-protein-coupled Y receptors in
      humans (hY(1), hY(2), hY(4), and hY(5)) and is activated by the so-called
      neuropeptide Y hormone family, which consists of three native peptide ligands
      named neuropeptide Y, pancreatic polypeptide, and peptide YY. We recently
      reported that one conserved aspartate residue in the third extracellular loop is
      essential for ligand binding in all four Y receptors, but binds the endogenous
      ligands in a different mode by interacting with different ligand arginine
      residues. By combining peptide synthesis to obtain chemically modified
      neuropeptide Y, peptide YY, and pancreatic polypeptide analogs, receptor
      mutagenesis, and receptor chimeras, we could trace binding and signaling to a
      molecular level. The data on the variation of the ligands and an overview of the
      currently known mutagenesis data are summarized and specific models for the
      binding mode of the three ligands in all four receptors are provided.

PMID- 18725087
TI  - SIR 2008 annual meeting film panel case: Arterial endofibrosis.

PMID- 18725088
TI  - SIR 2008 annual meeting film panel case: Abernethy malformation.

PMID- 18725089
TI  - SIR 2008 annual meeting film panel case: Alagille syndrome.

PMID- 18725090
TI  - Sixty-four-detector CT angiography of infrarenal aortic neck length and
      angulation: prospective analysis of interobserver variability.
AB  - PURPOSE: To quantify the interobserver variability of abdominal aortic aneurysm
      (AAA) neck length and angulation measurements. MATERIALS AND METHODS: A total of
      25 consecutive patients scheduled for endovascular AAA repair underwent follow-up
      64-row computed tomographic (CT) angiography in 0.625-mm collimation. AAA neck
      length and angulation were determined by four blinded, independent readers. AAA
      neck length was defined as the longitudinal distance between the first transverse
      CT slice directly distal to the lowermost renal artery and the first transverse
      CT slice that showed at least a 15% larger outer aortic wall diameter versus the
      diameter measured directly below the lowermost renal artery. Infrarenal AAA neck
      angulation was defined as the true angle between the longitudinal axis of the
      proximal AAA neck and the longitudinal axis of the AAA lumen as analyzed on three
      dimensional CT reconstructions. RESULTS: Mean deviation in aortic neck length
      determination was 32.3% and that in aortic neck angulation was 32.1%.
      Interobserver variability of aortic neck length and angulation measurements was
      considerable: in any reader combination, at least one measurement difference was
      outside the predefined limits of agreement. CONCLUSIONS: Assessment of the
      longitudinal extension and angulation of the infrarenal aortic neck is associated
      with substantial observer variability, even if measurement is carried out
      according to a standardized protocol. Further studies are mandatory to assess
      dedicated technical approaches to minimize variance in the determination of the
      longitudinal extension and angulation of the infrarenal aortic neck.

PMID- 18725091
TI  - Acute lower gastrointestinal hemorrhage: minimally invasive management with
      microcatheter embolization.
AB  - PURPOSE: To evaluate the efficacy of superselective embolization therapy in the
      management of acute lower gastrointestinal (LGI) hemorrhage, including any
      bleeding distal to the ligament of Treitz. MATERIALS AND METHODS: Between June
      and August 2007, 20 patients with acute LGI bleeding underwent superselective
      transcatheter arterial embolization (TAE) at the authors' institution. The
      bleeding had different causes. All patients were treated with use of
      microcatheters. The following embolic agents were used: microcoils (n = 16),
      polyvinyl alcohol (PVA) particles (n = 2), and a combination of microcoils and
      PVA particles (n = 2). Outcome measures included technical success (complete
      cessation of bleeding as documented at completion angiography), clinical success
      (resolution of signs or symptoms of LGI bleeding within 30 days after TAE), and
      the rate of major and minor complications. RESULTS: The identified bleeding
      sources were as follows: jejunal branch, branch of middle colic artery, branch of
      ileocolic artery, ileal branch, branch of left colic artery, branch of sigmoid
      artery, branch of the superior rectal artery, and branch of the middle rectal
      artery. Technical success with effective control of active bleeding was achieved
      in all patients (100%). Clinical success attributed to TAE was documented in 18
      of the 20 patients (90%). Major complications included death due to pulmonary
      embolism, heart infarction, and multiorgan failure in the 3rd week after TAE; a
      procedure-related colonic infarction occurred in one patient. A minor
      complication occurred in one patient who developed a groin hematoma. CONCLUSIONS:
      Superselective embolization may be used for effective, minimally invasive control
      of acute LGI bleeding.

PMID- 18725092
TI  - Embedded inferior vena cava filter removal: use of endobronchial forceps.
AB  - PURPOSE: Removing a retrievable inferior vena cava (IVC) filter can be extremely
      difficult with the use of standard techniques if the filter is tilted and
      embedded in the wall of the IVC. The use of rigid endobronchial forceps has been
      described in case reports to remove embedded IVC filters, and the present report
      describes the use of this technique to remove a series of tip-embedded IVC
      filters in two separate institutions. MATERIALS AND METHODS: The medical records
      were reviewed of 21 consecutive patients at two institutions who underwent
      attempted IVC filter removal with rigid endobronchial forceps over a 34-month
      period. The mean age of patients was 32.4 years (range, 14.1-54.1 y). The
      patients had the following filters: Recovery (n = 6), G2 (n = 10), Gunther Tulip
      (n = 4), and OptEase (n = 1). RESULTS: Rotational or biplane venography was used
      to confirm that the filters were tilted and embedded in the wall of the IVC in
      all 21 patients. Rigid endobronchial forceps were used successfully to remove 20
      embedded IVC filters in 21 patients. There was one case of failure to remove an
      embedded suprarenal G2 filter. There were no major complications. CONCLUSIONS:
      Rigid endobronchial forceps may be used as a reliable option for removal of
      embedded IVC filters.

PMID- 18725093
TI  - Safety and efficacy of CT-guided percutaneous cryoablation for renal cell
      carcinoma.
AB  - PURPOSE: Image-guided percutaneous cryoablation is a treatment alternative for
      selected patients with renal cell carcinoma (RCC). The objective of the present
      study was to present the safety and efficacy of percutaneous cryoablation.
      MATERIALS AND METHODS: The study included 51 lesions in 46 consecutive patients
      treated with computed tomography (CT)-guided percutaneous cryoablation. Results
      were based on 40 RCCs with follow-up. Patients had baseline history and physical
      and laboratory examinations and renal CT or magnetic resonance (MR) imaging and
      were followed every 3 months. Biopsy of all lesions was performed before or at
      the time of the procedure. Efficacy was defined as a complete lack of enhancement
      on follow-up contrast agent-enhanced CT or MR imaging. Lesion size was also
      followed and correlated with lack of enhancement. Short- and long-term
      complications were tabulated. RESULTS: The technical success rate was 100%, with
      20% of cases requiring some form of thermal protection of an adjacent organ.
      During follow-up (median, 28 weeks; range, 4-81 weeks), the efficacy rate was
      100% for lesions smaller than 7 cm. The incidence of significant complications
      was 18% (8% CTAE), mostly (10%) intercostal or genitofemoral nerve injury. All
      patients with complications recovered fully, and there were no mortalities. There
      was no change in creatinine levels, and no patient developed renal failure as a
      result of cryoablation. CONCLUSIONS: CT-guided percutaneous cryoablation resulted
      in complete response for lesions as large as 4 cm. It may also be a viable
      alternative for nonsurgical candidates with lesions as large as 7 cm. It has a
      high efficacy rate, and its modest complications are not only comparable to those
      of other treatment modalities, but also appear to be reversible.

PMID- 18725094
TI  - Comparison of percutaneous and surgical approaches to renal tumor ablation:
      metaanalysis of effectiveness and complication rates.
AB  - PURPOSE: To determine the effectiveness and complication rates of ablation of
      renal cell carcinoma (RCC) performed with a percutaneous approach versus a
      surgical approach. MATERIALS AND METHODS: A search performed on PubMed identified
      series of renal tumor ablations. Keywords searched included "radiofrequency"
      (RF), "cryoablation", "cryosurgery", "cryotherapy", "ablation", "renal",
      "kidney", and "RCC". Review articles were excluded from the search of English
      language literature from January 1996 through August 2006. Inclusion criteria
      were (i) more than one case, (ii) use of RF ablation or cryoablation, (iii)
      effectiveness based on follow-up imaging, and (iv) report of complication rate.
      Effectiveness was defined by the proportion of tumors without residual
      enhancement after one treatment session (ie, primary effectiveness) or after
      repeated treatments (ie, secondary effectiveness). Major complications were
      defined as events with substantial morbidity, disability, or increasing level of
      care. Metaanalysis was performed on primary effectiveness, secondary
      effectiveness, and major complication rates with a random-effects model.
      Differences were considered significant if the 95% CIs did not overlap. RESULTS:
      Forty-six series (28 percutaneous, 18 surgical) met all inclusion criteria. The
      primary effectiveness rate for the percutaneous group (87%) was significantly
      lower than that in the surgical group (94%; P < .05). The secondary effectiveness
      rate in the percutaneous treatment group (92%) was not significantly different
      from that in the surgical treatment group (95%; P > .05). The major complication
      rate in the percutaneous treatment group (3%) was significantly lower than that
      in the surgical treatment group (7%; P < .05). CONCLUSIONS: Based on a
      metaanalysis, when ablating renal tumors, a percutaneous approach was safer than
      an open or laparoscopic approach and was equally effective. However, more than
      one procedure was needed to treat the tumor completely.

PMID- 18725095
TI  - Factors associated with failed retrieval of the Gunther Tulip inferior vena cava
      filter.
AB  - PURPOSE: To identify potential factors associated with failed retrieval of the
      Gunther Tulip inferior vena cava (IVC) filter. MATERIALS AND METHODS: A
      retrospective review was performed of patients who underwent placement of the
      Gunther Tulip filter with at least one attempt at filter retrieval over a 3-year
      period. Patient demographics, filter dwell time, filter angulation, and filter
      leg protrusion were analyzed. RESULTS: A total of 188 patients were included in
      the study. Primary retrieval success was achieved in 166 patients (88.3%), for an
      overall retrieval success rate of 94.2%. The overall mean dwell time was 63 days,
      whereas the mean dwell time in cases of retrieval failure was 95.4 days. A total
      of seven filters were in place for longer than 6 months, four of which were
      successfully retrieved. The degree of filter tilt was not found to be
      significantly related to retrieval success (P = .36), even though filter
      angulation was commonly cited as a reason for retrieval failure. On venography,
      90.9% of filters that could not be retrieved showed leg protrusion beyond the
      lumen of the IVC. Finally, increasing patient age also correlated with retrieval
      failure (P = .01). CONCLUSIONS: Prolonged dwell time and increasing patient age
      are associated with failed filter retrieval. However, even filters in place for
      extended periods can be safely removed.

PMID- 18725096
TI  - Long-term outcome of percutaneous transhepatic therapy for benign bilioenteric
      anastomotic strictures.
AB  - PURPOSE: To evaluate the long-term outcomes of a percutaneous transhepatic
      approach in benign bilioenteric anastomoses with calibration of the stenosis to
      15 F and extended internal/external drainage. MATERIALS AND METHODS: Between
      February 2000 and May 2007, the efficacy of this percutaneous transhepatic
      procedure was retrospectively studied in 39 patients with benign postoperative
      bilioenteric anastomotic strictures. The main purpose of the protocol was to
      repair the anastomosis by calibration of the stenosis to 15 F with a silicone
      drain and perform internal/external drainage for at least 1 year. The follow-up
      period ranged from 12 to 65 months (mean, 34.4 months), and outcomes were
      classified according to the patient's clinical symptoms and laboratory parameters
      and the need for further interventions. RESULTS: The procedure was successful in
      38 of 39 patients. Four patients were lost to follow-up during or after drainage.
      The duration of drainage (41 internal catheters in 34 patients) ranged from 126
      days to 488 days (mean, 346 d). Twenty-seven patients had positive outcomes
      during the mean follow-up of 34 months, and six patients had negative outcomes.
      The bile duct patency probability according to the Kaplan-Meier method was and
      70.6% at 34 months after drain removal. CONCLUSIONS: Percutaneous treatment of
      benign biliary strictures with calibrated stent implantation and extended
      drainage has good long-term results and may be an effective alternative to
      surgery. Advantages over surgery are its minimal invasiveness and reduced risk of
      complications.

PMID- 18725097
TI  - The effect of rectal Foley catheterization on rectal bleeding rates after
      transrectal ultrasound-guided prostate biopsy.
AB  - PURPOSE: To assess whether Foley catheterization of the rectum after transrectal
      ultrasound (TRUS)-guided prostate biopsy decreases complication rates. MATERIALS
      AND METHODS: Between June 2000 and September 2006, 275 consecutive patients were
      evaluated after undergoing TRUS-guided prostate biopsy. All procedures were
      performed on an outpatient basis. Patients were divided into two groups. In the
      first group (n = 134), a Foley catheter was inserted into the rectum and inflated
      to 50 cm(3) after TRUS-guided biopsy. In the second group (n = 141),
      catheterization was performed without balloon placement. Rectal bleeding,
      hematuria, hematospermia, infection, and acute urinary retention rates were
      compared between groups. RESULTS: The mean ages of the patients were 63.3 years
      +/- 5.6 and 62.1 years +/- 7.2 years in the Foley catheter group and control
      group, respectively (P = .112). Hematuria, hematospermia, infection, and rectal
      bleeding occurred in 31 (23.1%), 30 (22.4), nine (6.7%), and two patients (1.5%),
      respectively, in the Foley catheter group; and in 36 (25.5%), 36 (25.5%), 11
      (7.8%), and 25 patients (17.7%), respectively, in the control group. The
      incidences of infection, hematuria, and hematospermia were not significantly
      different between groups (P > .05). In contrast, the rectal bleeding rate was
      significantly lower in the Foley catheter group (1.5%) than in the control group
      (17.7%; P = .001). CONCLUSIONS: Although it has no effect on other complications,
      TRUS-guided prostate biopsy with rectal Foley catheterization is a useful,
      practical method to decrease or prevent rectal bleeding.

PMID- 18725099
TI  - Feasibility of stent-graft placement with real-time MR fluoroscopy in a nonrigid
      aortic phantom.
AB  - PURPOSE: To evaluate the feasibility of using real-time magnetic resonance (MR)
      fluoroscopic guidance to place a stent-graft mounted on a guide wire in a
      nonrigid aortic phantom. MATERIALS AND METHODS: Real-time fast low-angle shot and
      true fast imaging with steady-state precession MR imaging sequences were used for
      device tracking. A modified fiber-optic guide wire and catheter embedded with
      titanium oxide in predefined positions were used for navigation in a homemade
      silicone thoracic aortic phantom. RESULTS: Susceptibility artifacts caused by the
      modified guide wire and catheters mounted in the descending thoracic aorta of the
      phantom were found to enable adequate determination of the guide wire position in
      relation to the surrounding anatomy and to cause no image distortion. Real-time
      MR imaging enabled visualization of both the vessel lumen and the delivery system
      with the mounted stent-graft, providing an image quality sufficient for
      successful localization of the lesion and deployment of the stent-graft.
      CONCLUSIONS: The results of this study prove the possibility of passive guidance
      in MR imaging-guided stent placement in vitro. The modified guide wire can be
      used with interventional commercial catheters and recent implant devices with
      selective tracking in the surrounding anatomy.

PMID- 18725098
TI  - Real-time MR imaging-guided laser atrial septal puncture in swine.
AB  - PURPOSE: The authors performed this study to report their initial preclinical
      experience with real-time magnetic resonance (MR) imaging-guided atrial septal
      puncture by using a MR imaging-conspicuous blunt laser catheter that perforates
      only when energized. MATERIALS AND METHODS: The authors customized a 0.9-mm
      clinical excimer laser catheter with a receiver coil to impart MR imaging
      visibility at 1.5 T. Seven swine underwent laser transseptal puncture under real
      time MR imaging. MR imaging signal-to-noise ratio profiles of the device were
      obtained in vitro. Tissue traversal force was tested with a calibrated meter.
      Position was corroborated with pressure measurements, oximetry, angiography, and
      necropsy. Intentional non-target perforation simulated serious complication.
      RESULTS: Embedded MR imaging antennae accurately reflected the position of the
      laser catheter tip and profile in vitro and in vivo. Despite having an increased
      profile from the microcoil, the 0.9-mm laser catheter traversed in vitro targets
      with similar force (0.22 N +/- 0.03) compared with the unmodified laser. Laser
      puncture of the atrial septum was successful and accurate in all animals. The
      laser was activated an average of 3.8 seconds +/- 0.4 before traversal. There
      were no sequelae after 6 hours of observation. Necropsy revealed 0.9-mm holes in
      the fossa ovalis in all animals. Intentional perforation of the aorta and atrial
      free wall was evident immediately. CONCLUSIONS: MR imaging-guided laser puncture
      of the interatrial septum is feasible in swine and offers controlled delivery of
      perforation energy by using an otherwise blunt catheter. Instantaneous soft
      tissue imaging provides immediate feedback on safety.

PMID- 18725100
TI  - Entrance surface dose during three-dimensional imaging with a flat-panel detector
      angiography system.
AB  - PURPOSE: To measure the entrance surface dose (ESD) during three-dimensional (3D)
      imaging of a phantom and evaluate a method to estimate ESD with use of dose-area
      product (DAP) values. MATERIALS AND METHODS: The present study used an
      angiographic unit with a digital flat-panel system for 3D imaging. DAP values and
      ESDs were evaluated on square phantoms with thicknesses of 12.0, 15.0, 18.0,
      21.0, and 25.0 cm with use of 5-second acquisitions. ESDs were measured on the
      lateral and posterior surfaces of the square phantom. DAP values and ESDs were
      also evaluated on a human-shaped phantom with various table heights, with ESDs
      measured on the phantom surfaces on the posterior centerline, right middle
      axillary line, and their midpoint. RESULTS: The posterior ESDs were 7.3 mGy, 12.1
      mGy, 18.8 mGy, 26.9 mGy, and 38.5 mGy for the square phantoms with thicknesses of
      12 cm, 15 cm, 18 cm, 21 cm, and 25 cm, respectively. The DAP and the posterior
      ESDs were correlated (r = 0.998, P < .0001). The regression equation was D = DAP
      x 0.0014, where D was the posterior ESD (mGy). For the human-shaped phantom, the
      posterolateral ESD tended to be slightly larger than the posteromedial ESD, with
      the differences less than 10%. The estimated doses based on this relationship
      were almost equal to the actual posterolateral doses for each table height.
      CONCLUSIONS: The ESD of a single 3D imaging study was considerably lower than the
      thresholds for radiation skin injuries. The DAP values are useful to estimate the
      maximum patient ESD during 3D imaging.

PMID- 18725101
TI  - Simulation in training: one-year experience using an efficiency index to assess
      interventional radiology fellow training status.
AB  - PURPOSE: To compare objective fellow and expert efficiency indices for an
      interventional radiology renal artery stenosis skill set with the use of a high
      fidelity simulator. MATERIALS AND METHODS: The Mentice VIST simulator was used
      for three different renal artery stenosis simulations of varying difficulty,
      which were used to grade performance. Fellows' indices at three intervals
      throughout 1 year were compared to expert baseline performance. Seventy-four
      simulated procedures were performed, 63 of which were captured as audiovisual
      recordings. Three levels of fellow experience were analyzed: 1, 6, and 12 months
      of dedicated interventional radiology fellowship. The recordings were compiled on
      a computer workstation and analyzed. Distinct measurable events in the procedures
      were identified with task analysis, and data regarding efficiency were extracted.
      Total scores were calculated as the product of procedure time, fluoroscopy time,
      tools, and contrast agent volume. The lowest scores, which reflected efficient
      use of tools, radiation, and time, were considered to indicate proficiency.
      Subjective analysis of participants' procedural errors was not included in this
      analysis. RESULTS: Fellows' mean scores diminished from 1 month to 12 months
      (42,960 at 1 month, 18,726 at 6 months, and 9,636 at 12 months). The experts'
      mean score was 4,660. In addition, the range of variance in score diminished with
      increasing experience (from a range of 5,940-120,156 at 1 month to 2,436-85,272
      at 6 months and 2,160-32,400 at 12 months). Expert scores ranged from 1,450 to
      10,800. CONCLUSIONS: Objective efficiency indices for simulated procedures can
      demonstrate scores directly comparable to the level of clinical experience.

PMID- 18725102
TI  - Hyperperfusion syndrome after external carotid artery stent placement in a case
      of bilateral internal carotid occlusion and external carotid stenosis.
AB  - The authors describe a patient with bilateral internal carotid artery occlusion,
      bilateral external carotid artery (ECA) stenosis, and suboptimal collateral
      circulation from the right ECA to the right cerebral hemisphere. The patient
      manifested clinical and radiographic signs of hyperperfusion syndrome following
      stent placement in the right ECA. This represents a rare case of a stent placed
      in the ECA of a patient in addition to the development of hyperperfusion syndrome
      after the procedure.

PMID- 18725103
TI  - Pubic bone cement osteoplasty for pubic insufficiency fractures.
AB  - The purpose of this report is to describe two cases of pubic bone insufficiency
      fractures refractory to conservative management treated with percutaneous cement
      osteoplasty. Both patients initially presented with severe pelvic pain and
      immobility and were treated conservatively without relief. The patients
      subsequently underwent percutaneous cement osteoplasty of the pubic bone and
      experienced complete pain relief immediately after the procedures. Both patients
      were followed up to 1 year, and were pain free throughout. Percutaneous cement
      osteoplasty may be an effective treatment for pubic bone insufficiency fractures.

PMID- 18725104
TI  - Two stiffs and a jerk.

PMID- 18725105
TI  - Re: Right renal artery in vivo stent fracture.

PMID- 18725106
TI  - An overview of hypofractionation and introduction to this issue of seminars in
      radiation oncology.

PMID- 18725107
TI  - Clinical experience shows that catastrophic late effects associated with ablative
      fractionation can be avoided by technological innovation.
AB  - The development of high-precision radiation therapy delivery technology has
      expedited a burgeoning interest in ultrabrief, intensified treatment courses that
      yield tumoricidal effects of unprecedented potency. Whereas novel medical
      treatments that provide enhanced clinical benefits can be associated with
      escalated risks of toxicity, it is absolutely essential for radiation oncologists
      to exercise caution and discipline as these new strategies are evaluated and
      implemented in the clinic. However, it is argued here that clinical experiences
      reported to date already support the durable safety and efficacy of so-called
      "ablative" schedules of radiation therapy. Furthermore, until the cancer problem
      is solved once and for all, it is the obligation of the radiation oncology
      community to continue to pursue new means to improve on results of the past.

PMID- 18725108
TI  - Some cases of severe normal tissue toxicity can be anticipated with ablated
      fractionated radiation with appropriate long-term follow-up.
AB  - As new technologies have allowed physicians to both better image and characterize
      malignant disease as well as deliver radiation dose with high precision and
      accuracy, there has been a resurgence in interest in hypofractionated or even
      single-fraction radiation therapy schemas. Late-reacting tissues have a low
      alpha/beta ratio (compared with early reacting tissues) and are therefore more
      sensitive to increments in fraction size. When we hypofractionate, we may lose
      some of the biological advantages associated with fractionation while we may
      simultaneously increase our risk of damaging late-responding normal tissues. The
      ideal 4 R's for tumor cells are exactly opposite those 4 R's ideally desired for
      normal tissues, and this represents the major dilemma to the practicing radiation
      oncologist. The long-term safety profile for modern hypofractionated radiation
      schemes will depend on the area and volume treated, the total dose delivered, and
      the level of baseline function observed before initiating radiation therapy.
      These issues are raised in the context of hypofractionation for central nervous
      system malignancies, lung cancers, pelvic malignancies, head and neck cancers,
      and breast cancers. If we are careful when choosing the site (and most
      importantly the volume), it is likely that hypofractionation may benefit our
      patients. However, history has taught us to be very careful when using
      hypofractionation to large volumes or when incorporating critical structures.
      With appropriate long-term follow-up, some cases of severe normal tissue toxicity
      can be anticipated. Hypofractionation should continue to be studied in randomized
      clinical trials, with a particular focus on careful follow-up.

PMID- 18725110
TI  - The linear-quadratic model is inappropriate to model high dose per fraction
      effects in radiosurgery.
AB  - The linear-quadratic (LQ) model is widely used to model the effect of total dose
      and dose per fraction in conventionally fractionated radiotherapy. Much of the
      data used to generate the model are obtained in vitro at doses well below those
      used in radiosurgery. Clinically, the LQ model often underestimates tumor control
      observed at radiosurgical doses. The underlying mechanisms implied by the LQ
      model do not reflect the vascular and stromal damage produced at the high doses
      per fraction encountered in radiosurgery and ignore the impact of radioresistant
      subpopulations of cells. The appropriate modeling of both tumor control and
      normal tissue toxicity in radiosurgery requires the application of emerging
      understanding of molecular-, cellular-, and tissue-level effects of high
      dose/fraction-ionizing radiation and the role of cancer stem cells.

PMID- 18725109
TI  - The linear-quadratic model is an appropriate methodology for determining
      isoeffective doses at large doses per fraction.
AB  - The tool most commonly used for quantitative predictions of dose/fractionation
      dependencies in radiotherapy is the mechanistically based linear-quadratic (LQ)
      model. The LQ formalism is now almost universally used for calculating
      radiotherapeutic isoeffect doses for different fractionation/protraction schemes.
      In summary, the LQ model has the following useful properties for predicting
      isoeffect doses: (1) it is a mechanistic, biologically based model; (2) it has
      sufficiently few parameters to be practical; (3) most other mechanistic models of
      cell killing predict the same fractionation dependencies as does the LQ model;
      (4) it has well-documented predictive properties for fractionation/dose-rate
      effects in the laboratory; and (5) it is reasonably well validated,
      experimentally and theoretically, up to about 10 Gy/fraction and would be
      reasonable for use up to about 18 Gy per fraction. To date, there is no evidence
      of problems when the LQ model has been applied in the clinic.

PMID- 18725111
TI  - Exploring the possibility of unique molecular, biological, and tissue effects
      with hypofractionated radiotherapy.
AB  - High-dose hypofractionated radiotherapy is feasible because of technological
      advances that allow for the precise delivery of radiation to a target volume that
      contains a limited amount of normal tissue. No longer constrained by the normal
      tissue response of large fields, very large doses of radiation can be delivered.
      However, with the application of high doses of radiation to very precise
      treatment volumes, we find ourselves wondering if the fundamental principles that
      govern conventional radiotherapy apply. The conventions of tumor hypoxia,
      reoxygenation, tumor repopulation, and intrinsic radiosensitivity are all likely
      to be unique or play new roles in tumor or normal tissue response. With that in
      mind, we highlight several facets of tumor or normal tissue response in which a
      better understanding of tumor biology and radiation biology could be beneficial
      to the application of high dose per fraction treatment modalities or in which
      caution should be exercised.

PMID- 18725112
TI  - Rationale, conduct, and outcome using hypofractionated radiotherapy in prostate
      cancer.
AB  - Hypofractionated radiation therapy for prostate cancer has become of increasing
      interest with the recognition of a potential improvement in therapeutic ratio
      with treatments delivered in larger-sized fractions. In addition, the associated
      reduction in fraction number produces attractive cost and patient convenience
      advantages as well. A still limited but growing number of hypofractionation
      trials have reported acceptable short-term levels of toxicity and biochemical
      control, but most have insufficient follow-up to ensure the long-term safety and
      efficacy of this approach. This situation will improve as many currently active
      trials mature, particularly several high-value randomized trials. In contrast,
      extreme hypofractionation, with schedules delivering only on the order of 5
      fractions, is truly in its infancy for prostate cancer, with extremely limited
      tolerance and efficacy information currently available. Several uncertainties in
      the radiobiology of hypofractionation mitigate for an organized, cautious
      investigational approach. The fractionation response (alpha/beta ratio) of
      prostate cancers and, for that matter, late-responding normal tissues, has yet to
      be rigorously defined. Additionally, the linear-quadratic (LQ) model used in the
      design of hypofractionation schedules is subject to its own uncertainties,
      particularly with respect to the upper limit of fraction sizes for which it
      remains valid. Contemporary dose-escalated radiation therapy is already highly
      effective, making it imperative that ongoing and future studies of
      hypofractionation be performed in carefully designed, randomized clinical trials.
      Clinical validation permitting, the adaptation of hypofractionation as a standard
      of care could profoundly influence future management of localized prostate
      cancer.

PMID- 18725113
TI  - Clinical experience using hypofractionated radiation schedules in breast cancer.
AB  - Hypofractionation is attractive for whole- or partial-breast irradiation because
      it permits treatment to be given with fewer fractions in a shorter period of time
      and at less cost. A number of cohort studies suggest that hypofractionation may
      be given to the whole breast safely and with good local control. Recent
      randomized trials have confirmed that hypofractioned whole-breast irradiation is
      equivalent to more conventional whole-breast irradiation with respect to local
      recurrence and cosmetic outcome. Recently, there has been a renewed interest in
      hypofractionation for the delivery of partial-breast irradiation using a number
      of techniques including high-dose rate brachytherapy, 3-dimensional conformal
      radiation using external-beam techniques, and intraoperative therapy. Early
      cohort studies report good local control and acceptable morbidity. Randomized
      trials are now underway to compare this approach to conventional whole-breast
      irradiation.

PMID- 18725114
TI  - The implementation of ablative hypofractionated radiotherapy for stereotactic
      treatments in the brain and body: observations on efficacy and toxicity in
      clinical practice.
AB  - Radiosurgery has a long history dating back to the 1950s. Only in the last decade
      or so have advances in radiation delivery and visualization allowed export of
      this paradigm to extracranial sites. This review evaluates the efficacy and
      safety of such ablative radiation courses using dose per fraction schedules of 10
      Gy or above. Retrospective published experience in functional and benign tumor
      radiosurgery is reviewed. Prospective controlled clinical trials in ablative
      cancer therapy of early-stage lung cancer and metastatic disease in the brain,
      liver, and spine are reviewed.

PMID- 18725115
TI  - Conflicts of interest, ghostwriters, and the importance of disclosure.

PMID- 18725116
TI  - The role of viscosupplementation in the ankle using hylan G-F 20.
AB  - The use of intra-articular injections of high molecular weight elastoviscous
      solutions of hyaluronan or hylans (cross-linked derivatives of hyaluronan) to
      treat arthritis is termed viscosupplementation. The function of
      viscosupplementation is to restore the rheologic properties of synovial fluid.
      Although anecdotal data exist, no long-term studies regarding the use of
      viscosupplementation in the ankle have been published to date. The goal of this
      clinical trial was to compare pain reduction following ankle arthroscopy versus
      that following ankle arthroscopy combined with weekly intra-articular
      instillation of hylan G-F 20 during the first 3 postoperative weeks. In the
      series of patients described in this report, we found that both treatment groups
      experienced statistically significantly decreased pain following the intervention
      (P = .002 and P = .0009 for the arthroscopy alone and arthroscopy plus hylan
      groups, respectively), and that those who received 3 intra-articular injections
      of hylan G-F 20 following ankle arthroscopy improved statistically significantly
      (P = .0014) more than did those who underwent arthroscopy as a sole therapy.
      These preliminary results suggest that viscosupplementation combined with
      arthroscopy may be more beneficial than arthroscopy alone, and provide further
      insight into the role of viscosupplementation in the treatment of ankle
      osteoarthritis. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 18725117
TI  - Analysis of gastrocnemius recession and medial column procedures as adjuncts in
      arthroereisis for the correction of pediatric pes planovalgus: a radiographic
      retrospective study.
AB  - The radiographic outcomes of 28 feet in 20 pediatric patients with pes
      planovalgus treated with subtalar arthroereisis, arthroereisis combined with
      gastrocnemius recession, or arthroereisis combined with gastrocnemius recession
      and medial column reconstruction were retrospectively analyzed. Preoperative and
      postoperative radiographic angles for talar declination, calcaneal inclination,
      and first metatarsal declination in the lateral view, and the angle formed
      between the longitudinal axis of the talus and the longitudinal axis of the
      lesser tarsus in the anteroposterior view were compared. Overall, analyses
      revealed statistically significant differences in the preoperative and
      postoperative radiographic angles for the 4 measured angles. Analysis by
      treatment group revealed statistically significant differences in correction of
      the angle measured in the anteroposterior view. Arthroereisis with gastrocnemius
      recession showed the greatest correction of this angle (median 19 degrees, range
      11 degrees to 34 degrees) compared with the other treatment groups. There were no
      statistically significant differences in the degree of correction of the
      calcaneal inclination or talar declination angles, whereas a statistically
      significant difference in the correction of first metatarsal declination was
      observed. The greatest degree of angular change was achieved with medial column
      reconstruction (median 7 degrees, range 0 degrees to 9 degrees). Gastrocnemius
      recession displayed a notable effect on the correction of transverse plane
      deformity when used as an adjunct to arthroereisis. However, medial column
      reconstruction has a negative impact on the degree of correction in the
      transverse plane when it is used as an adjunct to arthroereisis and gastrocnemius
      recession. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 18725118
TI  - Long-term results after operatively treated Achilles tendon rupture: fibrin glue
      versus suture.
AB  - The use of fibrin glue for repairing Achilles tendon ruptures was introduced in
      the 1980s. Although fibrin glue has been in regular use since that time, suturing
      remains the standard for surgical repair. Studies have indicated that, in the
      short term, fibrin glue is as effective as suturing. To date, there have been no
      long-term studies comparing the outcomes of these 2 techniques. This study
      compares the long-term results of surgical repair of Achilles tendon rupture with
      sutures versus fibrin glue. Forty-two patients who had undergone Achilles tendon
      repair with either suture or fibrin glue took part in a follow-up examination
      after an average of 12.1 years. The fibrin group consisted of 31 patients and the
      suture group consisted of 11 patients. Patients treated with fibrin glue reached
      a higher modified Thermann score (adapted from Weber), achieved equal results in
      an isokinetic force measurement, and showed fewer complications. The authors
      concluded that the use of fibrin glue for the repair of ruptured Achilles tendon
      is a suitable alternative to traditional sutures. LEVEL OF CLINICAL EVIDENCE: 2.

PMID- 18725119
TI  - Radiographic evaluation of endoscopic gastrocnemius recession, subtalar joint
      arthroereisis, and flexor tendon transfer for surgical correction of stage II
      posterior tibial tendon dysfunction: a pilot study.
AB  - The best procedure for surgical correction of stage II posterior tibial tendon
      dysfunction has long been a source of debate among foot and ankle surgeons. A
      combination of endoscopic gastrocnemius recession, subtalar joint arthroereisis,
      and flexor digitorum longus tendon transfer has been used in an attempt to avoid
      some of the complications seen with calcaneal osteotomies, and to allow an
      earlier return to function and weight bearing. A retrospective analysis of
      preoperative and postoperative radiographic changes in 10 patients for whom
      surgical correction of the deformity was performed between 2003 and 2006 is
      presented as a pilot study. Seven radiographic variables considered standard for
      the radiographic assessment of posterior tibial tendon dysfunction were measured.
      The outcome measure of interest was the return of radiographic variables to
      normal ranges following surgical correction of the deformity. In addition,
      preoperative and postoperative clinical outcomes were assessed to evaluate the
      long-term clinical benefits of this trio of procedures. Radiographic values were
      noted to return to normal ranges in all cases following this trio of surgical
      procedures; these changes were statistically significant (P < or = .05). These
      preliminary results suggest that this surgical combination provides satisfactory
      correction of deformity in patients presenting with stage II posterior tibial
      tendon dysfunction. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 18725120
TI  - Reliability of a computer-aided color-coded video-based system for clinical
      assessment of the foot.
AB  - There is a need for a user-friendly system that can provide quick and reliable
      assessment of foot disorders. The study described in this report was undertaken
      to determine the inter-rater and intra-rater reliability of a computer-aided,
      color-coded, video-based system developed for the assessment of foot alignment in
      patients with and without pes cavus deformity. Initially, 15 pedal angles were
      repetitively measured 7 times on 6 color-coded images of both feet, in 20 healthy
      adults. From the 7 repetitive measurements, the intra-class correlation was
      calculated and analysis of variance was used to estimate the minimum number of
      trials that would be necessary to identify a statistically significant difference
      in the measurements. To determine intra-rater reliability, 5 examiners evaluated
      a single set of data taken from 10 subjects. Additionally, data were obtained for
      20 subjects with pes cavus deformity. The average intra-class correlation
      coefficient (ICC) for the anglular measurements for 2 to 7 trials was 0.98 +/-
      0.06, while the intra-rater reliability was 0.90 +/- 0.14. No statistically
      significant differences were observed between right and left foot angles in able
      bodied subjects; whereas, in the pes cavus group, 8 different angular
      measurements were observed to be statistically significantly different. The
      results of this investigation indicate that a computer-aided, color-coded, video
      based system can be used to make reliable measurements of postural alignment in
      patients with and without pes cavus. LEVEL OF CLINICAL EVIDENCE: 5.

PMID- 18725121
TI  - Septic diabetic foot is not necessarily an indication for amputation.
AB  - Management of the septic foot is a challenge in diabetic patients, and this
      condition often progresses to amputation in an effort to alleviate otherwise
      incurable infection. We designed and followed a protocol for the management of
      the septic diabetic foot and, after 2 years (May 2004 through June 2006), we
      analyzed the data related to 31 septic feet of 139 patients. The treatment
      protocol consisted of blood glucose control, intravenous antibiotic therapy,
      controlling comorbidities, revascularization, ulcer drainage and irrigation,
      systematic debridement, dressing changes and wound care, and amputation if
      necessary. The outcomes of interest were amputation and limb salvage. The
      analyses showed that frequent drainage and debridement, along with
      revascularization when indicated and possible, resulted in 4 (12.9%) major (below
      the-knee) amputations and 3 transmetatarsal amputations. Of the 7 amputations, 3
      were associated with ischemia, 4 with neuropathy, and 1 with neuropathy and
      ischemia. In follow-up, 1 patient with a prior history of septic diabetic foot
      required major amputation. Based on these findings, it is concluded that the
      septic diabetic foot is not necessarily an indication for amputation, and
      aggressive management by means of metabolic and surgical care can lead to a
      favorable outcome. LEVEL OF CLINICAL EVIDENCE: 2.

PMID- 18725122
TI  - Levels of endothelial nitric oxide synthase and calcitonin gene-related peptide
      in the Charcot foot: a pilot study.
AB  - The pathogenesis of Charcot neuroarthropathy is unclear. To investigate the
      possibility that decreased levels of calcitonin gene-related peptide and
      endothelial nitric oxide synthase are involved in the process, we studied bone
      samples from healthy subjects (n = 4), subjects with diabetic neuropathy (n = 4),
      and subjects with Charcot neuroarthropathy (n = 4). A statistically significant
      difference was found in endothelial nitric oxide synthase expression between bone
      specimens in patients with diabetic neuropathy, Charcot neuroarthropathy, and
      normal bone (P = .008). A trend toward calcitonin gene-related peptide
      intensification was observed in normal bone as compared to diabetic neuropathy
      and Charcot neuroarthropathy bone specimens, but it did not reached statistical
      significance (P = .23). This pilot study suggests that abnormal calcitonin gene
      related peptide and endothelial nitric oxide synthase activity may play a role in
      the development of Charcot neuroarthropathy. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 18725123
TI  - Use of an acellular regenerative tissue matrix in combination with vacuum
      assisted closure therapy for treatment of a diabetic foot wound.
AB  - Diabetic foot ulcers can be difficult to treat for a variety of reasons, and may
      result in amputation. The use of skin grafts can often be a useful method of
      achieving wound coverage and subsequent healing of diabetic foot ulcers; however,
      this method of treatment requires creation of a donor site wound that adds to the
      patient's overall wound burden. Application of an acellular regenerative tissue
      matrix may eliminate the need for harvesting a skin graft in order to cover a
      nonhealing wound. The use of vacuum-assisted wound closure has been shown to
      promote an environment that enhances wound bed contraction and surface
      epithelialization. The combination of an acellular regenerative tissue matrix
      with vacuum-assisted wound closure can be used to promote healing in the
      management of a nonhealing diabetic foot wound. LEVEL OF CLINICAL EVIDENCE: x.

PMID- 18725124
TI  - Correction of severe foot and ankle contracture due to CRPS using external
      fixation and pain management: report of a pediatric case.
AB  - Complex regional pain syndrome-induced dystonia is a severe deformity that can
      affect the lower extremities and hinder ambulation. Although a number of
      conservative treatments have been described for this condition, we are not aware
      of any publications describing the use of surgical intervention for the treatment
      of this condition. In this report, we describe the case of a pediatric patient
      with a severe lower extremity deformity in conjunction with chronic pain
      syndrome. A concerted, interdisciplinary treatment approach was undertaken for
      the management of this patient, and this included contributions from a foot and
      ankle surgeon, a pain specialist, an internist, a physical therapist, and a
      psychiatrist. The primary goal of the treatment strategy was to recreate a
      plantigrade, weight-bearing lower extremity, while controlling pain. To this end,
      gradual correction of deformity was achieved using an external fixator and, by 6
      months after the surgery, the patient was for the first time in years ambulating
      on the realigned lower extremity. After 3 years of follow-up, she maintained an
      activity level that was equal to that which she enjoyed before the injury. LEVEL
      OF CLINICAL EVIDENCE: 4.

PMID- 18725125
TI  - Bilateral ankle dislocation without malleolar fracture.
AB  - Dislocation of the ankle joint without a concomitant malleolar fracture is rare.
      With all reported cases to date being unilateral injuries, we present the case of
      a 28-year-old male who sustained bilateral ankle dislocations without associated
      ankle fractures following a road traffic accident. Ten months after the trauma,
      the patient had returned to work with minimal sequelae related to the injury. To
      our knowledge, this is the first case of its kind to be reported. LEVEL OF
      CLINICAL EVIDENCE: 4.

PMID- 18725126
TI  - Ankle arthroplasty alternatives with allograft and external fixation: preliminary
      clinical outcome.
AB  - Tibiotalar joint reconstruction for the treatment of osteoarthritic and post
      traumatic arthritic joint remains controversial and unsatisfactory. While the
      current literature recommends joint arthrodesis as a gold standard, current
      developments in allograft technology may aid in the repair of articular damage;
      avoid any metallic implant wear, failure, and revision; and preserve normal
      musculoskeletal biomechanics. The purpose of this retrospective study was to
      report the early clinical outcomes of ankle arthroplasty with allograft and with
      the application of a monolateral external fixation in the treatment of ankle
      arthritis. Eighteen patients (18 ankles, n = 18) with end-stage ankle arthritis,
      underwent surgical intervention. The mean preoperative AOFAS score was 32.0 +/-
      1.1 (30-33) while the postop was 87.33 +/- 7.6 (81-97) (P = .000). There were no
      complications associated with the allograft material. There were also no
      complications with the external fixator. The early clinical outcome results
      provided an optimistic view of this procedure as another alternative treatment
      for the arthritic ankle, with subjective patient improvement and satisfaction, as
      well as a statistically significant and functionally increased range of motion
      and joint space and objective improvements. Allograft implantation with external
      fixation for the arthritic tibiotalar joint provided encouraging preliminary
      results and patient satisfaction mirroring current outcomes from shoulder and
      animal studies. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 18725127
TI  - Revisional total ankle arthroplasty because of a large tibial bone cyst.
AB  - Osteoarthritis of the ankle can occur secondary to alteration of the articular
      surfaces, such as in the posttraumatic setting, or because of gradual
      degeneration as a result of biomechanical dysfunction. Although primary
      inflammatory ankle arthritis rarely occurs, the majority of cases of ankle
      osteoarthritis occur after bony trauma, ligamentous injury, congenital deformity,
      or previous surgical intervention. Although ankle arthrodesis was shown to be
      successful and reliable, and although it remains the gold standard for surgical
      intervention after nonsurgical care of the arthritic ankle has been exhausted, a
      reasonable return to a dynamic lifestyle can be limited by fusion of the ankle.
      With the ever-increasing prevalence of favorable objective outcomes after
      implantation of late-model ankle endoprostheses, total ankle arthroplasty has
      become a popular alternative to arthrodesis. As the number of total ankle
      replacements increases in the population, particularly in cases involving younger
      and more active patients, surgeons will encounter more cases that require
      revisional total ankle replacement. We describe a patient who underwent the
      exchange of one total ankle endoprosthesis for another, in the presence of a
      large cyst about the tibial component of the implant. LEVEL OF CLINICAL EVIDENCE:
      4.

PMID- 18725128
TI  - Nocardiosis causing pedal actinomycetoma: a case report and review of the
      literature.
AB  - Madura foot is rarely encountered in clinical practice in the United States, and
      a recent review of the biomedical literature revealed only 24 cases reported
      worldwide since 1981. In this report, we describe the case of a patient who
      presented with an advanced pedal Nocardia mycetoma. Although this condition is
      not unheard of, we felt that the rarity of the condition warranted reporting.
      LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 18725129
TI  - Spontaneous rupture of the anterior tibial tendon in a diabetic patient: results
      of operative treatment.
AB  - Spontaneous rupture of the tibialis anterior tendon is infrequently seen as a
      clinical entity. In this report, we describe the case of a diabetic neuropathic
      patient that underwent successful surgical repair of a spontaneously ruptured
      tibialis anterior tendon with no other factors that would render the tendon
      susceptible to injury or rupture. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 18725130
TI  - Application of a constrained external fixator frame for treatment of a fixed
      equinus contracture.
AB  - Ankle equinus can result from congenital, traumatic, neurological, and
      pathological etiologies. Corrective methods have been described in the literature
      using a combination of soft tissue releases or osseous procedures with reported
      complications. We present a case report of a patient with a post-traumatic fixed
      equinus deformity of 28 degrees at maximum dorsiflexion, treated successfully
      through gradual correction using a modified constrained external fixator. The
      patient maintained a rectus foot and was able to perform all daily activities at
      the final follow-up. Fixed equinus deformities can be difficult to manage.
      Gradual correction with an external fixator is a reasonable treatment option.
      LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 18725131
TI  - Reconstruction of the extruded talus with large allograft interfaces: a report of
      3 cases.
AB  - Although replant of the extruded talus would be preferable at the time of initial
      management, some patients present with a talus that had not been recovered. A
      series of 3 cases of the extruded talus that were reconstructed with large
      allograft interfaces are presented. Two of the cases had femoral head allografts
      and the other used morcellized cancellous allograft. Several orthobiologic
      substances were used in various proportions for each case. All 3 resulted in a
      solid union with minimal shortening of the extremity. LEVEL OF CLINICAL EVIDENCE:
      4.

PMID- 18725132
TI  - Glomus tumor in the second toe: a clinical insight.
AB  - Glomus tumors are rare benign tumors commonly occurring in the digits of the
      hand. Surprisingly, considering the fingertips are of a similar make-up to the
      toes, there have been few reports of glomus tumor in the toes. The present case
      highlights a glomus tumor observed in the right second toe of a 56-year-old
      Indian female who presented with the classical triad of spontaneous pain, cold
      hypersensitivity, and pressure tenderness. There was a delay in diagnosis for
      approximately 18 years by various general practitioners who were not aware of the
      rare presentation of the glomus tumor. The tumor, which measured 5 x 3 mm, was
      excised from the nail bed of the toe. Histopathological inspection confirmed the
      diagnosis of glomus tumor. We believe that reporting this rare case may make
      clinicians more aware of this unusual diagnosis. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 18725133
TI  - Recurrent pedal hobnail (Dabska-retiform) hemangioendothelioma with forefoot
      reconstructive surgery using a digital fillet flap.
AB  - An 8-year-old female presented with a recurrent hobnail (Dabska-retiform)
      hemangioendothelioma of her right foot. After initial tumor excision and
      subsequent recurrence, the patient underwent a successful tumor resection and
      forefoot reconstruction using a fillet of second digit flap. In an attempt to
      create a plantigrade foot, while sufficiently removing this rare pedal tumor, the
      authors employed the use of a fillet of second digit flap. Specific surgical
      techniques and the histopathological assessment of this rare vascular neoplasm
      are discussed. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 18725134
TI  - Osteotome axial twist (OAT) technique: a simple method for exposing arthritic
      foot joints in preparation for arthrodesis.

PMID- 18725135
TI  - Drs. Clements, Motley, Garrett, and Carpenter reply to Drs. Ozturk, Ozkan, and
      Yalcin.

PMID- 18725136
TI  - Biliary interventions--Part 1. Introduction.

PMID- 18725137
TI  - Cholecystostomy and transcholecystic biliary access.
AB  - Percutaneous cholecystostomy represents a minimally invasive procedure for
      providing gallbladder decompression, often in critically ill patient populations.
      Indications for this procedure include calculous and acalculous cholecystitis,
      gallbladder perforation, malignant obstruction, percutaneous biliary stone
      removal, biliary duct drainage, and diagnostic imaging of the gallbladder and
      biliary ductal system. In addition, gallbladder access provided by percutaneous
      cholecystostomy may serve to carry additional procedures, such as cholangiograms,
      gallstone dissolution, and lithotripsy. Review of prior imaging studies including
      ultrasound, CT, and hepatobiliary scans are essential to planning the procedure,
      by helping to determine the access route: transhepatic versus transperitoneal.
      The transhepatic route is preferred in cases of large ascities, bowel
      interposition, and offers the advantage of greater catheter stability. On the
      other hand, the transperitoneal route is preferred in the setting of coagulopathy
      and liver disease. Initial access is gained via insertion of an 18- to 22-gauge
      needle, followed by use of the Seldinger technique or trocar system to
      catheterize the gallbladder. Overall technical success rate for percutaneous
      cholecystostomy is greater than 95%. Clinical improvement is achieved in 56 to
      93% of patients. Complications occur in 3 to 13% of cases and are mainly acute
      and minor. Major complications such as bile peritonitis, significant hemorrhage,
      and hemo/pneumothorax affect less than 5% of patients. However, sepsis and
      reported 30-day mortality rates of up to 25% are usually related to underlying
      morbidities in critically ill patients. Catheters may be removed once the fistula
      track has matured.

PMID- 18725138
TI  - Percutaneous transhepatic biliary drainage.
AB  - Over the past three decades, endoscopic and percutaneous biliary drainage have
      become readily available in most hospital settings and these minimally invasive
      techniques have revolutionized the treatment of patients with biliary
      obstruction. In the past, treatment of biliary obstruction had required surgery
      under general anesthesia and an extended hospital stay. Currently, the same
      patient can most often be treated either endoscopically as an outpatient or
      during a short hospital stay after percutaneous drainage under moderate sedation.
      This article reviews the indications and technique of percutaneous transhepatic
      cholangiography and biliary drainage.

PMID- 18725139
TI  - Transhepatic techniques for accessing the biliary tract.
AB  - Gaining access to the biliary tract by minimal invasive image-guided techniques
      is the forefront procedure for interventionalists to manage biliary disease. The
      technical know how and learned maneuvers are the fundamental skill sets of an
      interventional radiologist. This article details the technical maneuvers that can
      be utilized to gain access to the biliary tract with a needle and/or
      catheter/wire combinations. These techniques include (1) fluoroscopic-guided
      needle localization from a percutaneous transhepatic approach, (2) different
      types of wire access/entry into the biliary system, (3) the use of intrabiliary
      snares as targets for secondary/additional biliary access, (4) recannulating
      transhepatic biliary tracts after inadvertent discontinuation of percutaneous
      biliary drains, and (5) ultrasound-guided left-sided biliary duct access.

PMID- 18725140
TI  - Management of malignant biliary obstruction.
AB  - Malignant bile duct obstruction is not uncommon, particularly in the later stages
      of disease, and may result in significant deterioration in the patient's quality
      of life, particularly if the patient becomes pruritic. Patients who have
      undergone previous intervention such as surgery with bilioenteric bypass,
      sphincterotomy, or endoscopic retrograde cholangiopancreatography may present
      with cholangitis. In addition, obstructive jaundice may preclude the use of
      certain chemotherapeutic agents either because of increased toxicity or because
      they require hepatic metabolism or excretion. This article discusses the
      indications for drainage in this patient population, technical considerations
      that may be unique to this patient population, and technical suggestions for
      performing drainage that may be helpful.

PMID- 18725141
TI  - Biliary complications after orthotopic liver transplantation.
AB  - Liver transplantation has made many advances since its inception in the early
      1970s. Despite volumes of basic science and clinical research related to liver
      transplantation, biliary complications continue to present the interventional
      radiologist with challenging cases in all transplant centers. Biliary
      complications can range from minor complications such as contained bile leaks to
      severe complications such as biliary necrosis resulting from hepatic artery
      thrombosis. Minor complications may require minimal or no intervention, whereas
      the more severe complications can require urgent surgery. To treat biliary
      complications such as anastomotic strictures, nonanastomotic strictures, biliary
      leaks, sludge or biliary necrosis, an accurate diagnosis must first be obtained.
      One must also be aware of how these complications can impair both allograft and
      transplant patient survival. With this information one can then plan a treatment
      knowing the potential success rates of specific treatments. Using proper
      technique with this information at hand can greatly increase the success rate in
      treating the spectrum of biliary complications. Interventional radiology serves a
      critical role in diagnosis and treatment of these liver transplant biliary
      complications and is important to the success of all transplant programs.

PMID- 18725142
TI  - Management of bleeding after percutaneous transhepatic cholangiography or
      transhepatic biliary drain placement.
AB  - Bleeding complications occur in 2 to 3% of percutaneous transhepatic biliary
      drains. These complications include: hemothorax, hemoperitoneum, subcapsular
      hepatic bleeding, hemobilia, melena, and bleeding from the percutaneous biliary
      drain. The bleeding sites can be classified into (1) perihepatic bleed sites
      (hemothorax, hemoperitoneum, subcapsular hepatic hematoma), (2) gastrointestinal
      bleeding (hemobilia and/or melena), and (3) bleeding from the percutaneous
      biliary drain itself, which is the most common clinical presentation. There are
      several bleeding sources. These include skin-bleeds, intercostal artery, portal
      vein, hepatic vein, and the hepatic artery. There are a variety of maneuvers that
      can be utilized in the management of bleeding percutaneous biliary drains. These
      include tractography, angiography, tract embolization, arterial embolization, and
      tract site changes. This article proposes a protocol for approaching bleeding
      complications after percutaneous biliary drain placement and details the
      diagnostic and therapeutic procedures in the management of these bleeding
      complications.

PMID- 18725143
TI  - A kaleidoscope of science.

PMID- 18725145
TI  - The third decade of the Journal of Nutrition Education (1988-1997): vibrant
      expansion in research content, audiences, and topics for nutrition education.

PMID- 18725146
TI  - Nutrition students improve attitudes after a guided experiential assignment with
      older adults.
AB  - OBJECTIVE: Develop, implement, and evaluate an intervention (a guided
      experiential assignment) to improve nutrition students' attitudes toward working
      with older adults. DESIGN: A quasi-experimental design with an additional
      qualitative component (mixed methods). SETTING: A North Central land-grant
      university. PARTICIPANTS: 100 college students from an upper-level community
      nutrition course. INTERVENTION: Students were randomly assigned to conduct a
      guided experiential assignment (dietary behavior change project) working with
      either an older adult (intervention, n = 52) or a younger adult (comparison, n =
      48). Each student conducted 3 client interviews and completed a project report by
      responding to reflective questions about changes in beliefs, values, and self
      efficacy in working with older adults. MAIN OUTCOME: The primary outcome was
      attitudes toward older adults as changed in reference to students' beliefs,
      values, and self-efficacy in working with other adults. Additional outcomes were
      knowledge of aging and interest in working with older adults. ANALYSIS: General
      linear model multivariate/univariate analysis and content analysis were conducted
      on the quantitative and qualitative data, respectively. RESULTS: The intervention
      group had significantly increased scores on attitudes toward older adults
      relative to the comparison group. This finding appeared as a result of changes in
      beliefs about older adults and the increased value and self-efficacy in working
      with this group by most students in the intervention group. CONCLUSION AND
      IMPLICATIONS: Completion of a guided experiential assignment with older adults in
      the community was an effective method to improve students' attitudes. Used in the
      curriculum for nutrition students, this technique might help to improve both
      attitudes toward and self-efficacy in working with older adults.

PMID- 18725147
TI  - Internet-based interventions have potential to affect short-term mediators and
      indicators of dietary behavior of young adults.
AB  - OBJECTIVE: Evaluate a theory-based, Internet-delivered nutrition education
      module. DESIGN: Randomized, treatment-control design with pre-post intervention
      assessments. SETTING AND PARTICIPANTS: Convenience sample of 160 young adults
      (aged 18-24) recruited by community educators in 4 states. Study completers (n =
      96) included a mix of racial/ethnic groups and family demographics, but were
      predominately white females without children. INTERVENTION: A Transtheoretical
      Model (TTM)-based, stage-tailored Internet program, F&V (Fruit & Vegetable)
      Express Bites, was delivered to treatment group participants; controls received
      nontailored messages in a comparable format. MAIN OUTCOME MEASURES AND ANALYSIS:
      TTM constructs at baseline, immediately postviewing, and at 30-day follow-up were
      compared via chi-square, McNemar's test, and logistic regression. Qualitative use
      and acceptability indicators were collected postviewing (treatment only).
      RESULTS: Of baseline respondents, 86.5% completed the study. At follow-up, self
      efficacy, decisional balance, and selected processes improved for both groups,
      with only marginal advantages for the theory-based version. Fruit and vegetable
      consumption changes were similar for both groups. Qualitative measures of
      knowledge, confidence, and motivation improved (not measured for controls).
      Favorable ratings of treatment program acceptability and personal relevance were
      reported. CONCLUSIONS AND IMPLICATIONS: The Internet is a favorable option for
      reaching young adults with nutrition messages. This study did not identify strong
      advantages of theory-based tailoring, especially for fruit consumption, which had
      weaker barriers than vegetable consumption among this target audience.

PMID- 18725148
TI  - Nutrient intake and nutritional status indicators of participant and
      nonparticipant pupils of a parent-supported school lunch program in Kenya.
AB  - OBJECTIVE: To compare nutrient intake and indicators of nutritional status of
      western Kenyan pupil participants and nonparticipants of a parent-supported
      school lunch program. DESIGN: Pupils and their caregivers were interviewed to
      assess their 24-hour dietary intake and the socioeconomic status of the family.
      Pupils' weights and heights were measured. SETTING: Eight randomly selected
      schools with parent-supported school lunch programs in Emuhaya, western Kenya.
      PARTICIPANTS: 320 pupils aged between 10 and 12 years in Standard 5 and Standard
      6 were disaggregated into school lunch participants (n = 160) and nonparticipants
      (n = 160). MAIN OUTCOME MEASURES: Pupils' energy and protein intake; nutritional
      status indicators; household socioeconomic characteristics. ANALYSIS: Independent
      t test for comparison of group means; chi-square for socioeconomic
      characteristics. Level of significance was P = .05. RESULTS: Energy and protein
      consumption of participants was higher than that of the nonparticipants. Severe
      underweight, severe stunting, and severe wasting were significantly higher among
      the nonparticipants. Hunger and a higher absenteeism rate from school were more
      commonly reported among the nonparticipants. CONCLUSIONS AND IMPLICATIONS: This
      study demonstrates the interaction of poverty, nutrition status, and education.
      To improve the nutritional status and academic performance of the students whose
      parents cannot afford to participate in school lunch programs, funding from
      external sources is essential.

PMID- 18725149
TI  - Validating the food behavior questions from the elementary school SPAN
      questionnaire.
AB  - BACKGROUND: The School Physical Activity and Nutrition (SPAN) questionnaire was
      developed as a surveillance instrument to measure physical activity, nutrition
      attitudes, and dietary and physical activity behaviors in children and
      adolescents. The SPAN questionnaire has 2 versions. OBJECTIVE: This study was
      conducted to evaluate the validity of food consumption items from the elementary
      school version of the SPAN questionnaire. DESIGN: Validity was assessed by
      comparing food items selected on the questionnaire with food items reported from
      a single 24-hour recall covering the same reference period. SETTING: 5 elementary
      schools in Indiana. PARTICIPANTS: Fourth-grade student volunteers (N = 121) from
      5 elementary schools. MAIN OUTCOME MEASURE: Agreement between responses to SPAN
      questionnaire items and reference values obtained through 24-hour dietary recall.
      ANALYSIS: The agreement between the questionnaire and the 24-hour recall was
      measured using Spearman correlation, percentage agreement, and kappa statistic.
      RESULTS: Correlation between SPAN item responses and recall data ranged from .25
      (bread and related products) to .67 (gravy). The percentage agreement ranged from
      26% (bread and related products) to 90% (gravy). The kappa statistic varied from
      .06 (chocolate candy) to .60 (beans). CONCLUSIONS AND IMPLICATIONS: Results from
      this study indicate that the SPAN questionnaire can be administered in the
      classroom quickly and easily to measure many previous day dietary behaviors of
      fourth graders. However, questions addressing consumption of "vegetables,"
      "candy," and "snacks" need further investigation.

PMID- 18725150
TI  - Discrepancy between snack choice intentions and behavior.
AB  - OBJECTIVE: To investigate dietary constructs that affect the discrepancy between
      intentioned and actual snack choice. DESIGN: Participants indicated their
      intentioned snack choice from a set of 4 snacks (2 healthful, 2 unhealthful). One
      week later, they actually chose a snack from the same set. Within 1 week after
      the actual choice, they completed a questionnaire that evaluated several dietary
      constructs. SETTING: Worksite cafeterias. PARTICIPANTS: Office employees in the
      Netherlands (N = 585, 65% male, mean age 39.6 years [standard deviation = 9.2],
      83% highly educated). MAIN OUTCOME MEASURES: Snack choice intentions and actual
      snack choices (healthful vs unhealthful). Demographic and dietary constructs.
      ANALYSIS: Student t tests, chi-square tests, and logistic regression (P < .05).
      RESULTS: Forty-nine percent of the participants (n = 285) intended to choose a
      healthful snack. Of this group, 27% (n = 78) chose an unhealthful snack instead.
      Ninety-two percent (n = 276) of the unhealthful intenders did indeed choose an
      unhealthful snack. None of the dietary constructs significantly predicted the
      failure to enact a healthful snack choice intention. CONCLUSIONS AND
      IMPLICATIONS: Although a substantial discrepancy between healthful intentions and
      actual snack choice was demonstrated, the evaluated constructs do not adequately
      measure the psychological process by which intention is converted into practice.
      Further studies are required to further investigate this process.

PMID- 18725151
TI  - How to strengthen and enhance WIC nutrition education.

PMID- 18725152
TI  - A Family Bookbag program reaches parents with messages about healthful eating and
      physical activity and improves family reading time.

PMID- 18725153
TI  - Changes in physical activity from walking to school.

PMID- 18725154
TI  - The Milwaukee Inventory for the Dimensions of Adult Skin Picking (MIDAS): initial
      development and psychometric properties.
AB  - This article describes the development and initial psychometric properties of the
      Milwaukee Inventory for the Dimensions of Adult Skin picking (MIDAS), a measure
      designed to assess "automatic" and "focused" skin picking. Data were collected
      from 92 participants who completed an anonymous internet-based survey. Results of
      an exploratory factor analysis revealed a two-factor solution. Factors 1
      ("focused" picking scale) and 2 ("automatic" picking scale) each consisted of 6
      items, and preliminary data demonstrated adequate internal consistency, good
      construct validity, and good discriminant validity. The MIDAS provides
      researchers with a reliable and valid assessment of "automatic" and "focused"
      skin picking.

PMID- 18725155
TI  - CYP11A1 and CYP17 promoter polymorphisms associate with hyperandrogenemia in
      polycystic ovary syndrome.
AB  - OBJECTIVE: To analyze promoter regions of CYP11A1 and CYP17 for putative
      variations in a defined group of women with polycystic ovary syndrome (PCOS) and
      to study their association with androgen levels. DESIGN: Retrospective study.
      SETTING: A secondary referral center for infertility at National Institute for
      Research in Reproductive Health, Mumbai, India. PATIENT(S): One hundred women
      whose condition was diagnosed on the basis of the Rotterdam consensus were
      compared against 100 age-matched controls. INTERVENTION(S): A single sample of
      blood was collected after overnight fast on day 3 of the menstrual cycle. MAIN
      OUTCOME MEASURE(S): Plasma levels of T, androstenedione, 17alpha
      hydroxyprogesterone, and DHEAS and nucleotide sequence of promoter regions of
      CYP11A1 and CYP17 genes. RESULT(S): Polymorphisms in promoter regions of the two
      key androgen-regulating genes, CYP11A1 and CYP17, were found to be significantly
      associated with T levels in the cohort of well-characterized PCOS cases as
      compared with controls. The significance was greater in the PCOS cases with both
      the polymorphisms. CONCLUSION(S): Our study carried out in a defined group of
      Indian women with PCOS suggests for the first time an individual, as well as
      combined, association of polymorphisms in CYP11A1 and CYP17 promoters with T
      levels.

PMID- 18725156
TI  - Cost-minimization analysis of jumbo reusable forceps versus disposable forceps in
      a high-volume ambulatory endoscopy center.
AB  - BACKGROUND: Endoscopists worldwide are faced with the challenge of choosing the
      most cost-effective and durable equipment. There are limited data comparing the 2
      major options for endoscopic forceps: disposable and reusable. Disposable forceps
      are marketed as the cost-effective alternative to reusable forceps. OBJECTIVE:
      This study was designed to provide a prospective assessment of the survival and
      cost of reusable versus disposable forceps to allow more educated decisions when
      purchasing endoscopic equipment. DESIGN: A 24-month prospective study in a high
      volume ambulatory endoscopy center (AEC) with 71 Olympus jumbo reusable forceps
      (OJRF). A "cost of OJRF per procedure" was generated to compare to the estimated
      cost of disposable forceps per procedure. SETTING: Gastrointestinal Associates PA
      of Jackson, Mississippi, which performs approximately 24,000 outpatient
      procedures per year. PATIENTS: General patient population of this AEC undergoing
      colonoscopy. MAIN OUTCOME MEASUREMENTS: Mean cost of forceps per procedure and
      survival of reusable forceps. Cost was derived from purchase price, cleaning
      costs, repair/maintenance costs, and number of uses. RESULTS: Over the 24-month
      period, the total cost per procedure was $3.27. The mean number of uses per OJRF
      was 166.3. Sixty-eight percent of the forceps required no repair throughout the 2
      year study, and only 1 forceps was deemed beyond repair. For comparison,
      disposable forceps were assigned a cost per procedure of $10.00 on the basis of
      conservative market price. Over a 2-year period this cost-per-procedure
      difference resulted in a cost savings of $79,482. LIMITATIONS: Failure to
      determine the average life-span of OJRF because 98% were still functioning
      properly after 2 years and an average of 166.3 procedures. Evaluation did not
      include storage and disposal costs, which would add a miniscule additional cost
      to disposable costs. The study also does not address some of the other arguments
      for disposables such as performance (quality of specimen) compared with
      reusables. The estimated average number of uses and durability was only studied
      for the OJRF. Other forceps may have different average cost per use and
      durability. CONCLUSIONS: In a large-volume AEC, OJRF are vastly more durable than
      resusable forceps reported in prior studies and are vastly more cost-effective
      than disposable forceps. A longer study period would have only revealed more
      dramatic cost savings and durability.

PMID- 18725157
TI  - EMR of large, sessile, sporadic nonampullary duodenal adenomas: technical aspects
      and long-term outcome (with videos).
AB  - BACKGROUND: EMR is a viable alternative to surgery for removal of large mucosal
      neoplastic lesions of the entire GI tract. Few studies have, however, been
      published on the safety, efficacy, and technical aspects of EMR in the duodenum.
      OBJECTIVE: Our purpose was to evaluate the efficacy and safety of EMR of large
      (>15 mm) duodenal adenomas. DESIGN: Retrospective evaluation of a defined patient
      cohort. SETTING: Tertiary academic referral center. PATIENTS: Patients with large
      (>15 mm) sporadic nonampullary duodenal adenomas managed by a standardized
      technique who were referred by other specialist endoscopists for endoscopic
      treatment. METHODS: Five-year data from patients undergoing EMR for large
      duodenal adenomas were reviewed retrospectively. Immediate and delayed
      complications were recorded. RESULTS: Twenty-one lesions were removed by EMR in
      23 patients (mean age 62.2 years, 13 female, 10 male). The mean size of lesions
      resected was 27.6 mm (median 20 mm, range 15-60 mm). Post-EMR histologic
      examination revealed mucosal adenocarcinoma in 1, low-grade tubulovillous adenoma
      (TVA) in 16, high- or focal high-grade TVA in 3 patients, and 1 with both high
      grade TVA and carcinoid. EMR was performed successfully in 18 patients during a
      single session. Two patients required 2 sessions and 1 required 3 sessions for
      complete resection. The median follow-up was 13 months (range 4-44 months).
      During follow-up, 5 patients had minor residual adenomas that were treated
      successfully with snare resection and/or argon plasma coagulation. One patient
      had EMR site bleeding. There were no perforations. LIMITATION: Retrospective
      study. CONCLUSION: EMR for large sporadic nonampullary duodenal adenomas is a
      safe and effective technique.

PMID- 18725158
TI  - Preferred designs, outcomes, and analysis strategies for treatment trials in
      idiopathic recurrent acute pancreatitis.

PMID- 18725159
TI  - A closer look at same-day bidirectional endoscopy.
AB  - BACKGROUND: Same-day bidirectional endoscopy (BDE) is commonly used in clinical
      practice. OBJECTIVE: Our purpose was to determine the frequency, patient
      demographics, indications, and significant endoscopic findings for patients
      undergoing BDE. DESIGN: Retrospective study with a national endoscopic database.
      SETTING: Diverse clinical practice settings in the United States, including 75%
      from private practice. PATIENTS: A total of 591,074 adult patients had upper or
      lower endoscopy; 66,265 patients (11.2%) with same-day BDE and a subgroup (n =
      9067) with a common indication for both upper and lower examinations are the
      subjects of this analysis. MAIN OUTCOME MEASUREMENTS: Age, sex, and procedure
      indication were analyzed in all subjects. Significant endoscopic findings were
      measured in patients with a single indication of anemia, a positive fecal occult
      blood test (FOBT), or abdominal pain/dyspepsia (pain) for both upper and lower
      endoscopy. METHODS: The Clinical Outcomes Research Initiative (CORI) national
      endoscopic database was analyzed to determine the number of patients who
      underwent same-day BDE between 2000 and 2004. Patients with a single indication
      of anemia, positive fecal occult blood test (FOBT), or abdominal pain/dyspepsia
      (pain) on both EGD and colonoscopy were included for the analysis of endoscopic
      findings. Significant upper GI findings were defined as suspected malignancy,
      arteriovenous malformation (AVM), ulcer, Barrett's esophagus, and stricture.
      Significant lower GI findings included suspected malignancy, polyp >9 mm, and
      AVM. RESULTS: A total of 591,074 patients had upper and/or lower endoscopy;
      66,265 patients (11.2%) had same-day BDE. The majority of patients were female
      (52.1%), and the mean age of patients with BDE was 60.8 years. A total of 6538
      patients (9.9%) had anemia, 1169 (1.8%) had a positive FOBT, and 1360 (2.1%) had
      pain as the sole indication for both examinations. After adjustment for age and
      sex, significant findings were higher in patients with anemia than in those with
      pain (odds ratio 1.89; 95% CI, 1.59-2.26) and for patients with positive FOBT
      versus pain (odds ratio 1.83; 95% CI, 1.48-2.26). LIMITATIONS: Retrospective
      analysis with possible bias. Fewer patients with pain had significant findings
      compared to the other two groups (P value <.0001). CONCLUSIONS: More than 10% of
      patients undergoing upper or lower endoscopy receive same-day BDE. BDE commonly
      revealed important conditions in patients with anemia or positive FOBT.
      Bidirectional endoscopy commonly revealed important pathology in patients with
      anemia or positive FOBT. Patients with pain had a lower prevalence of serious
      findings compared to the other groups studied. The benefits of BDE in patients
      with pain are uncertain and require additional investigation.

PMID- 18725160
TI  - Feeding sows with high fibre diet around farrowing and early lactation: impact on
      intestinal activity, energy balance related parameters and litter performance.
AB  - The effects of fibre in diets for periparturient sows are poorly documented.
      Three weeks before farrowing, 41 sows (LACT) were fed a diet containing 3.8%
      crude fibre. Other 40 sows (FIBRE) received a diet containing 7% crude fibre. We
      estimated the intestinal activity of the sows with a daily qualitative evaluation
      of their faeces. The FIBRE group had a qualitative faeces score value of 2.1+/
      1.3 and the LACT group had a value of 1.2+/-1.1 (P<0.001). Individual daily water
      consumption was higher in the FIBRE group than in the LACT group (P<0.001).
      Piglet weight gain at day 5 was higher in the FIBRE group (P<0.05). The energy
      balance related parameters did not differ between the treatments. Concluding,
      diets containing more fibre can be successfully used around farrowing reducing
      prolonged constipation of sows with no negative effect on their energy balance
      related parameters.

PMID- 18725161
TI  - Selective removal of estrogenic compounds by molecular imprinted polymer (MIP).
AB  - A molecular imprinted polymer (MIP) was synthesized and used for selective
      removal of estrogenic compounds. The study on the mass balance of template as
      well as template leakage revealed that almost all the template could be extracted
      out of the polymer and no template leakage could be detected in aqueous solution.
      In acetonitrile, MIP could adsorb more E2 than non-template imprinted polymer
      (NIP) by more than 3.5 times. In aqueous solution, MIP showed reduced selectivity
      for E2 with a 10% difference in adsorption capacity between MIP and NIP. With an
      initial E1, E2, EE2 and BPA concentration of 4 microM in aqueous solution and
      adsorbent concentrations of 0.01-0.5mg/mL, the maximum adsorption capacities of
      MIP for E1, E2, EE2 and BPA were 92.8, 95.8, 115.4 and 57.4 micromol/g polymer,
      respectively. According to the adsorption isotherms for E1, E2, EE2 and BPA, a
      physical adsorption model containing three types of binding sites, namely,
      specific binding site, semi-specific binding site and non-specific binding site,
      was proposed to interpret the adsorption performance of MIP.

PMID- 18725162
TI  - An alternative to specious linearization of environmental models.
AB  - The solution of a number of environmental models is incorrectly obtained by
      linearizing a nonlinear analytical solution. The linearization can yield a model
      that includes a common variable on both sides of the equal sign (i.e., ratio
      analysis), which in calibration causes highly inflated goodness-of-fit
      statistics. These specious practices continue likely because of tradition, i.e.,
      "that is the way it is done". Goodness-of-fit statistics that result from these
      erroneous practices do not accurately reflect the actual prediction accuracy of
      the model. Additionally, the linearly calibrated coefficients can be poor
      estimators of the true coefficients. The goal of this paper is to demonstrate the
      pitfalls of models based on ratio analyses. Several environmental models are used
      to demonstrate the erroneous procedure. Monte Carlo simulation is used to show
      the distribution of the true correlation coefficient and compare it to the
      distribution that results from the erroneous linearization. Linearization can
      produce correlation coefficients above 0.9 when the actual correlation is near 0.
      Nonlinear least squares algorithms can be used to more accurately fit nonlinear
      data to nonlinear models.

PMID- 18725163
TI  - Alcohol production through volatile fatty acids reduction with hydrogen as
      electron donor by mixed cultures.
AB  - In this research we demonstrated a new method to produce alcohols. It was
      experimentally feasible to produce ethanol, propanol and butanol from solely
      volatile fatty acids (VFAs) with hydrogen as electron donor. In batch tests, VFAs
      such as acetic, propionic and butyric acids were reduced by mixed microbial
      cultures with a headspace of 1.5 bar of hydrogen. Observed alcohol concentrations
      were 3.69+/-0.25 mM of ethanol, 8.08+/-0.85 mM of propanol and 3.66+/-0.05 mM of
      n-butanol. The conversion efficiency based on the electron balance was 55.1+/
      5.6% with acetate as substrate, 50.3+/-4.7% with propionate and 46.7+/-2.2% with
      n-butyrate. Methane was the most predominant by-product in each batch experiment,
      33.6+/-9.6% of VFA and hydrogen was converted to methane with acetate as
      substrate; which was 27.1+/-7.1% with propionate and 36.6+/-2.2% with n-butyrate.
      This VFAs reducing renewable fuel production process does not require
      carbohydrates like fermentable sugars, but uses biomass with high water content
      or low sugar content that is unsuitable as feedstock for current fermentation
      processes. This so-called low-grade biomass is abundantly present in many
      agricultural areas and is economically very attractive feedstock for the
      production of biofuels.

PMID- 18725164
TI  - Particle-associated polycyclic aromatic hydrocarbons in the atmospheric
      environment of Zonguldak, Turkey.
AB  - Airborne fine (PM(2.5)) and coarse (PM(2.5-10)) particulate matter was collected
      from January to December in 2007 in Zonguldak, Turkey using dichotomous Partisol
      2025 sampler. Fourteen selected polycyclic aromatic hydrocarbons (PAHs) in
      particulate matter were determined simultaneously by high-performance liquid
      chromatography with fluorescence detection (HPLC-FL) and seasonal distributions
      were examined. The source identification of PAHs in airborne particulates was
      performed by principal component analysis (PCA) in combination with diagnostic
      ratios. The predominant PAHs determined in PM(2.5) were pyrene, fluoranthene,
      benzo[a]anthracene, chrysene, benzo[b]fluoranthene and benzo[a]pyrene. The total
      concentrations of PAHs were up to 464.0 ng m(-3) in fine and 28.0 ng m(-3) in
      coarse fraction in winter, whereas in summer times were up to 22.9 and 3.0 ng m(
      3) respectively. Approximately 93.3% of total PAHs concentration was determined
      in PM(2.5) in winter and 84.0% in summer. The concentration levels of PAHs
      fluctuate significantly within a year with higher means and peak concentrations
      in the winter compared to that of summer times. Higher benzo(a)pyrene-equivalent
      (BaPE) concentrations of PAHs were obtained for PM(2.5) especially in winter. The
      results obtained from PCA in combination with diagnostic ratios revealed that
      coal combustion and vehicle emissions were the major pollutant sources for both
      PM(2.5) and PM(2.5-10) associated PAHs in studied area. Two principal components
      for PM(2.5) and three for PM(2.5-10) were identified and these accounted for 89.4
      and 85.2% of the total variance respectively. The emissions from coal combustion
      were estimated to be the main source of PAHs in the ambient air particulates with
      contributions of 80.8% of total variance for PM(2.5) and 53.8% for PM(2.5-10).

PMID- 18725165
TI  - Parish classification or dwelling coordinate for exposure assessment in
      environmental epidemiology - a comparative study using Geographical Information
      System.
AB  - BACKGROUND: Two previous epidemiological studies on the incidence of total
      malignancies in Sweden after the Chernobyl accident have shown consistently
      increased risks. The first study used an analogue map on (137)Cs from 1986 to
      classify individuals in terms of the parish they lived in. In the second study,
      dwelling coordinates were matched to a digital map from the year 2000 to assess
      the individual exposure. To establish the accuracy of the exposure assessment
      using the larger unit of parish, instead of coordinates, we decided to compare
      the methods. METHODS: On the analogue map eleven isolines on the deposition of
      (137)Cs (kBq/m(2)) were used to classify all individuals in each of the 450
      parishes. Using the digital map, by contrast, each dwelling with its inhabitants
      could be matched to (137)Cs deposition at a coordinate level. A population
      weighted average of (137)Cs deposition was calculated for each parish. In total,
      1,126,960 individuals and 450 parishes were included and analysed into six
      different exposure categories. RESULTS: Using the new parish exposure index, 111
      out of the 450 parishes were reclassified as a result of the increased resolution
      of the digital map (86 parishes) or unequal distribution of the population
      compared with the deposition (25 parishes). Seventy-five per cent of the parishes
      remained in the same exposure category as on the analogue map. CONCLUSION: Using
      dwelling coordinates for exposure assessment may not always be superior to parish
      classification. Nor is it always a cost-effective way of estimating the exposure,
      especially if the exposure in a parish is relatively homogenous or if parishes
      can be merged into broader categories with little intra-parish difference.

PMID- 18725166
TI  - Embryonal rhabdomyosarcoma of the uterine cervix in a 41-year-old woman treated
      with radical hysterectomy and adjuvant chemotherapy.
AB  - BACKGROUND: Cervical embryonal rhabdomyosarcoma (ERMS) mostly affects young
      girls. The current treatment protocols are based on trials done on patients under
      21 years old. ERMS in women over 40 is rare, and studies on treatment and outcome
      are limited. CASE: We report a case of a 41 year-old woman with cervical ERMS who
      was treated with radical hysterectomy followed by chemotherapy. She is currently
      disease-free. CONCLUSION: Cervical ERMS in women over the age of 40 can be
      treated using protocols established for the pediatric population.

PMID- 18725167
TI  - A less radical treatment option to the fertility-sparing radical trachelectomy in
      patients with stage I cervical cancer.
AB  - The purpose of the two pilot studies was to determine the feasibility and safety
      of using less-radical fertility-preserving surgery: laparoscopic lymphadenectomy
      with sentinel lymph node identification (SLNI) followed by a large cone or simple
      trachelectomy (LAP-I protocol) and the LAP-III protocol, which includes
      neoadjuvant chemotherapy (NAC). LAP-I: Forty women underwent laparoscopic SLNI,
      frozen-section analysis, and a complete pelvic lymphadenectomy as the first step
      of treatment. Seven days after final histopathological processing of dissected
      nodes, a large cone or simple vaginal trachelectomy was performed in patients
      with negative nodes. Nine women had a tumor larger than 20 mm, prompting the
      administration of three cycles of NAC before surgery. LAP-I: Six frozen sections
      were positive (15%). In these cases, a type III Wertheim was immediately
      performed. There were no false-negative SLNs. There was one central recurrence,
      but after chemoradiation therapy, there was no evidence of the disease 62 months
      post-treatment. Twenty-four of 32 women whose reproductive ability had been
      maintained tried to conceive. Of these 24 women, 17 became pregnant (71%
      pregnancy rate). Eleven mothers gave birth to 12 children (1 at 24 weeks, 1 at 34
      weeks, 1 at 36 weeks, and 9 between 37 and 39 weeks). LAP-III: Nine patients were
      included. In 7 of these 9 women, reproductive ability was maintained, with 3
      women becoming pregnant (1 full term and 2 ongoing). SLNI improves safety in
      fertility-sparing surgery. Large cone or simple trachelectomy combined with
      laparoscopic pelvic lymphadenectomy can be a feasible method that yields a high,
      successful pregnancy rate. NAC followed by fertility-sparing surgery is an
      experimental alternative treatment for larger tumors.

PMID- 18725168
TI  - Practical application of seminal plasma.
AB  - Natural mating deposits a large number of sperm in a high volume of seminal
      plasma. Semen processed for AI has the seminal plasma greatly diluted, and
      processing of boar sperm for cryopreservation removes all seminal plasma. Boar
      sperm were evaluated for the impact of seminal plasma on the functional status of
      boar sperm. Seminal plasma prevented or reversed capacitation in frozen-thawed
      boar sperm. However, supplementing frozen-thawed semen doses with 10% seminal
      plasma did not significantly affect the number of sperm found in the utero-tubal
      sperm reservoir, nor did it affect farrowing rates.

PMID- 18725169
TI  - Molecular dynamics study of heparin based coatings.
AB  - Heparin based surface coatings can be used to improve the biocompatibility of
      metallic surfaces such as vascular stents. Here, we report molecular dynamics
      simulations of a macromolecular conjugate of heparin used to prepare such
      surfaces. The structural properties of the heparin conjugate are investigated for
      different degrees of hydration, to allow comparison with spectroscopic results.
      The simulations show that the polymer becomes more compact with an increasing
      degree of inter-chain interactions as the hydration increases. This is also
      accompanied by changes in the interaction patterns among the heparin chains,
      where counter ions become looser associated with the disaccharide units and their
      strong interactions can be partly replaced by water molecules and heparin
      hydroxyl groups. The structural information that can be obtained from computer
      simulations of this type of coatings can be very valuable for understanding and
      further development of functional interfaces, since very little is known
      experimentally regarding their detailed structural properties.

PMID- 18725170
TI  - Cardiomyocyte-targeted siRNA delivery by prostaglandin E(2)-Fas siRNA polyplexes
      formulated with reducible poly(amido amine) for preventing cardiomyocyte
      apoptosis.
AB  - A cardiomyocyte-targeted Fas siRNA delivery system was developed using
      prostaglandin E(2) (PGE(2))-modified siRNA polyplexes formed by a reducible
      poly(amido amine) to inhibit cardiomyocyte apoptosis. PGE(2), which was used as a
      specific ligand for cardiomyocyte targeting, was conjugated to the terminal-end
      of the sense siRNA (PGE(2)-siRNA). The reducible cationic copolymer, synthesized
      via Michael-type polyaddition of 1,6-diaminohexane and cystamine bis-acrylamide
      (poly(DAH/CBA)), tightly condensed the PGE(2)-siRNA conjugate to form nanosize
      polyplexes having a diameter of 100-150 nm. The PGE(2)-siRNA/poly(DAH/CBA)
      polyplexes decomplexed to release PGE(2)-siRNA in a cytosolic reducing
      environment due to the degradation of the reducible poly(DAH/CBA). The cellular
      uptake of the PGE(2)-siRNA/poly(DAH/CBA) polyplex was increased in rat
      cardiomyocytes (H9C2 cells) due to PGE(2) receptor-mediated endocytosis. When
      H9C2 cells were transfected with siRNA against Fas, a key regulator of ischemia
      induced apoptosis, the PGE(2)-Fas siRNA/poly(DAH/CBA) polyplex delivery system
      led to a significant increase in Fas gene silencing, resulting in inhibition of
      cardiomyocyte apoptosis. The PGE(2)-Fas siRNA/poly(DAH/CBA) polyplex did not
      induce interferon-alpha in peripheral blood mononuclear cells. These results
      suggest that the PGE(2)-Fas siRNA/poly(DAH/CBA) polyplex formulation may be
      clinically applicable as a cardiomyocyte-targeted Fas siRNA delivery system to
      inhibit apoptosis in cardiovascular disease.

PMID- 18725171
TI  - Hydrochemistry of urban groundwater, Seoul, Korea: the impact of subway tunnels
      on groundwater quality.
AB  - Hydrogeologic and hydrochemical data for subway tunnel seepage waters in Seoul
      (Republic of Korea) were examined to understand the effect of underground tunnels
      on the degradation of urban groundwater. A very large quantity of groundwater (up
      to 63 million m3 year(-1)) is discharged into subway tunnels with a total length
      of 287 km, resulting in a significant drop of the local groundwater table and the
      abandonment of groundwater wells. For the tunnel seepage water samples (n = 72)
      collected from 43 subway stations, at least one parameter among pathogenic
      microbes (total coliform, heterotrophic bacteria), dissolved Mn and Fe, NH4+,
      NO3(-), turbidity, and color exceeded the Korean Drinking Water Standards.
      Locally, tunnel seepage water was enriched in dissolved Mn (avg. 0.70 mg L(-1),
      max. 5.58 mg L(-1)), in addition to dissolved Fe, NH4+, and pathogenic microbes,
      likely due to significant inflow of sewage water from broken or leaking sewer
      pipes. Geochemical modeling of redox reactions was conducted to simulate the
      characteristic hydrochemistry of subway tunnel seepage. The results show that
      variations in the reducing conditions occur in urban groundwater, dependent upon
      the amount of organic matter-rich municipal sewage contaminating the aquifer. The
      organic matter facilitates the reduction and dissolution of Mn- and Fe-bearing
      solids in aquifers and/or tunnel construction materials, resulting in the
      successive increase of dissolved Mn and Fe. The present study clearly
      demonstrates that locally significant deterioration of urban groundwater is
      caused by a series of interlinked hydrogeologic and hydrochemical changes induced
      by underground tunnels.

PMID- 18725172
TI  - Evaluation of contamination by blood aerosols produced during various healthcare
      procedures.
AB  - This study aimed to quantify the blood content of aerosols produced during
      dental, maxillofacial and autopsy procedures and to identify those activities
      which involve the greatest risk of infection due to exposure to blood-containing
      aerosols. A total of 132 air samples were taken in several dental cubicles, a
      maxillofacial operating theatre and an autopsy room. The concentration of
      haemoglobin (Hb) in the samples was quantified and, for each day of sampling, the
      concentration of blood/m(3) of air aspirated (muL blood/m(3) air) was calculated.
      Hb was detected in 38.64% of samples. The mean concentration of Hb in the samples
      was 0.10+/-0.19 microg Hb/m(3) of aspirated air, with a range of 0-0.72 microg
      Hb/m(3). No statistically significant differences in the concentration of blood
      aerosol per m(3) of aspirated air were noted among the three types of activity
      analysed (P>0.05). Although there is, as yet, no concrete proof of the risk of
      infection through blood-containing aerosols, minimising the production and
      dispersal of aerosols and spatters is strongly recommended.

PMID- 18725173
TI  - Investigation of the antioxidant properties of some new 4-hydroxycoumarin
      derivatives.
AB  - The aim of this investigation was to measure the activity of four 4
      hydroxycoumarin derivatives - three of them were described before and one was
      newly synthesized. The substances were ethyl 2-[(4-hydroxy-2-oxo-2H-chromen-3
      yl)(4-hydroxyphenyl)methyl]-3-oxobutanoate (SS-14), 4-[1-(4-hydroxy-2-oxo-2H
      chromen-3-yl)-2-(ethoxycarbonyl)-3-oxobutyl]benzoic acid (SS-17), ethyl 2-[(4
      hydroxy-2-oxo-2H-chromen-3-yl)(3-nitrophenyl)methyl]-3-oxobutanoate (SS-21) and
      ethyl 2-[(3,4,5-trimethoxyphenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-3
      oxobutanoate (T-2). The synthesis of T-2 consists of two steps. First step was
      Knoevenagel reaction between 3,4,5-trimethoxybenzaldehyde and ethylacetoacetate.
      Ethyl 2-(3,4,5-trimethoxy)-phenylmethyleneacetoacetate was the product. Second
      step was Michael addition reaction between the latter product and 4
      hydroxycoumarin. All the compounds were tested in vitro for antioxidant activity
      in hypochlorous system. The assay was based on the luminol-dependent
      chemiluminescence of free radicals, which decreased in the presence of 4
      hydroxycoumarin derivative. Compound SS-14 (ethyl 2-[(4-hydroxy-2-oxo-2H-chromen
      3-yl)(4-hydroxyphenyl)methyl]-3-oxobutanoate) expresses the best scavenger
      activity at the highest concentration (10(-4)mol/L).

PMID- 18725174
TI  - Structure-based analysis reveals hydration changes induced by arginine
      hydrochloride.
AB  - Arginine hydrochloride has been used to suppress protein aggregation during
      refolding and in various other applications. We investigated the structure of hen
      egg-white lysozyme (HEL) and solvent molecules in arginine hydrochloride solution
      by X-ray crystallography. Neither the backbone nor side-chain structure of HEL
      was altered by the presence of arginine hydrochloride. In addition, no stably
      bound arginine molecules were observed. The number of hydration water molecules,
      however, changed with the arginine hydrochloride concentration. We suggest that
      arginine hydrochloride suppresses protein aggregation by altering the hydration
      structure and the transient binding of arginine molecules that could not be
      observed.

PMID- 18725175
TI  - Calcium, calcium-sensing receptor and colon cancer.
AB  - There is much evidence that dietary Ca(2+) loading reduces colon cell
      proliferation and carcinogenesis in humans and rodents, but during carcinogenesis
      it becomes ineffective or even tumor-promoting. We are beginning to see how
      Ca(2+) balances the continuous massive cell production in colon crypts by driving
      the terminal differentiation and eventually the apoptosis of the cells mainly on
      the mucosal surface, and how this Ca(2+) control is lost during colon
      carcinogenesis. The rapid proliferation of the transit-amplifying (TA) progeny of
      the colon stem cells is driven by the so-called "Wnt" signaling mechanism, which
      involves the stimulation of proliferogenic genes such as those for c-Myc and
      cyclin D1 and the silencing of the gene for the cell cycle-stopping
      p21(Cip1/WAF1) protein by nuclear beta-catenin*Tcf-4 complexes. TA cells avoid
      mitotic damage and premature apoptosis by expressing the protein survivin. It
      appears that TA cell cycling stops and terminal differentiation starts when the
      cells reach a higher level in the crypt where there is enough lumenal Ca(2+) to
      stimulate the expression and activation of CaSRs (Ca(2+)-sensing receptors), the
      signals from which stimulate the expression of E-cadherin. Along with this, the
      APC (adenomatous polyposis coli) protein appears and some of it enters the
      nucleus. There it makes the TA cells susceptible to the eventual apoptotic
      balancing by stopping survivin expression and the beta-catenin*Tcf-4 complex from
      driving further cell cycling by releasing beta-catenin from the nucleus, and
      delivering it to cytoplasmic APC*axin*GSK-3beta complexes for ultimate
      proteasomal destruction. Cytoplasmic beta-catenin is then prevented from
      returning to the nucleus by either being intercepted and destroyed by
      APC*axin*GSK-3beta complexes or locked by the emerging E-cadherin into membrane
      adherens junctions which tie the cell into the sheet of proliferatively shut-down
      cells with APC-dependent cytoskeletons moving to the mouth of the crypt and onto
      the flat mucosal surface. A common first step in sporadic colon carcinogenesis is
      the loss of functional APC which disorients upwardly directed migration and
      causes the retention of nuclear beta-catenin and proliferogenic beta-catenin*Tcf
      4 complexes as well as genomic instability. Eventually the balance between cell
      proliferation and terminal differentiation and death is radically tipped in
      favour of proliferation by the appearance of apoptosis-resistant, survivin
      expressing clones of Ca(2+)-insensitive cells which are locked into the
      proliferative, mutation-prone mode because of CaSR-disabling gene mutations which
      prevent the stimulation of E-cadherin expression and terminal differentiation.

PMID- 18725176
TI  - The enhanced adsorption of dibenzothiophene onto cerium/nickel-exchanged zeolite
      Y.
AB  - The investigations for selective adsorption of dibenzothiophene (DBT) over Ce/Ni
      loaded Y zeolites with the emphasis on the effect of Ce as a cocation in the Ni
      loaded Y zeolite are carried out in an attempt to produce more effective
      adsorbents for the desulfurization from transportation fuels. The promotional
      effects of Ce and coexisting toluene in the model fuel as well as contact time
      and adsorbent dose on the adsorptive performance were examined. The sulfur uptake
      strongly depends on the amount of Ce in the zeolite structure. The sorption data
      is varied according to both Langmuir and Freundlich isotherm models. The maximum
      sorption capacity by theoretically calculation is 22.2mg/g at 25 degrees C. The
      Langmuir constants b=5.82 mL/mg and the Freundlich constants K=1.042 L/mg and
      1/n=0.4 are evaluated. Ni/Ce-loaded Y zeolites (NiCeY) and NiY, CeY, NaY zeolites
      were used as adsorbents for the removal of DBT from model fuel containing 500
      mg/L sulfur with 5 vol% of toluene by a batch method under ambient conditions.
      NiCeY exhibits higher adsorptive selectivity for DBT than NiY and CeY, indicating
      that NiCeY is a more effective adsorbent to remove sulfur compounds from
      transportation fuels.

PMID- 18725177
TI  - Dedifferentiated thyroid cancer: a therapeutic challenge.
AB  - Human papillary dedifferentiated thyroid cancer (HPDTC) represents a therapeutic
      dilemma. Targeted therapy (RET proto-oncogene or BRAF-targeting drugs) are
      promising treatments for HPDTC. Also PPARg agonists are another exciting field
      for redifferentiating therapy of HPDTC. However, even if many new approaches for
      the therapy of HPDTC are emerging, until now a significant clinical impact on
      survival by the use of these drugs is still lacking. In the future, the
      identification of patients who are likely to benefit from each therapeutic option
      will be important. In this view particular importance should be given to
      development of primary cells from the single patient by fine needle aspiration
      samples, as recently observed in anaplastic thyroid cancer. In fact,
      chemosensitivity tests in primary tumoral cells may help in detecting responsive
      patients and in preventing the administration of inactive drugs to those
      unresponsive.

PMID- 18725178
TI  - Cognitive impairment in bipolar disorder: neurodevelopment or neurodegeneration?
      An ECNP expert meeting report.
AB  - This is a report arising from an ECNP expert meeting. Recent studies have
      focussed on cognitive problems in manic-depressive illness and a few have
      addressed premorbid neuropsychological functioning. The results are not fully
      consistent but seem to point to a neurodegenerative model, rather than a
      neurodevelopmental one, for some cognitive domains. There is agreement that
      cognitive dysfunction is highly correlated with psychosocial functioning. The
      neurobiological and clinical implications of recent findings will be discussed.
      Treatments to reduce subsyndromal symptoms and relapses may indirectly improve
      neurocognitive deficits and this should be better documented. Moreover,
      neurocognitive impairment in bipolar disorder should be considered a potential
      therapeutic target, so that research should focus on new drugs and psychological
      interventions, including neurocognitive rehabilitation, addressed to improve not
      only the cognition but also the functional outcome of this population.

PMID- 18725179
TI  - Synthesis and biological evaluation of 2-amino-3-(3',4',5'-trimethoxybenzoyl)-6
      substituted-4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivatives as antimitotic
      agents and inhibitors of tubulin polymerization.
AB  - Microtubules are among the most successful targets of compounds potentially
      useful for cancer therapy. A new series of inhibitors of tubulin polymerization
      based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)-4,5,6,7
      tetrahydrothieno[b]pyridine molecular skeleton was synthesized and evaluated for
      antiproliferative activity, inhibition of tubulin polymerization, and cell cycle
      effects. The most promising compound in this series was 2-amino-3-(3,4,5
      trimethoxybenzoyl)-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[b]pyridine, which
      inhibits cancer cell growth with IC(50)-values ranging from 25 to 90 nM against a
      panel of four cancer cell lines, and interacts strongly with tubulin by binding
      to the colchicine site. In this series of N(6)-carbamate derivatives, any further
      increase in the length and in the size of the alkyl chain resulted in reduced
      activity.

PMID- 18725180
TI  - Novel anticancer agents, kayeassamins C-I from the flower of Kayea assamica of
      Myanmar.
AB  - A CHCl3-soluble fraction of 70% EtOH extract of the flower of Kayea assamica from
      Myanmar exhibited 100% preferential cytotoxicity (PC(100)) against human
      pancreatic cancer PANC-1 cells under nutrient-deprived conditions at 1 microg/mL.
      Bioassay-guided fractionation and isolation afforded nine new coumarins,
      kayeassamins A (8), B (9), and C-I (1-7), together with nine known coumarins (10
      18). The structures of these compounds were identified by extensive spectroscopic
      techniques as well as by comparison with published data. Absolute configuration
      at C-1' of 1 was established as S-configuration by the modified Mosher method.
      All the isolates were evaluated for their in vitro preferential cytotoxicity
      using novel anti-austerity strategy. Among them, the novel coumarins,
      kayeassamins A (8), B (9), D (2), E (3), and G (5) exhibited the most potent
      preferential cytotoxicity (PC(100) 1 microM) in a concentration- and time
      dependent manner and induced apoptosis-like morphological changes of PANC-1 cells
      within 24 h of treatment. Based on the observed cytotoxicity, structure-activity
      relationships have been established.

PMID- 18725181
TI  - Disaggregation of amphotericin B by sodium deoxycholate micellar aggregates.
AB  - Amphotericin B (AmB) is present as aggregates in aqueous media. Sodium
      deoxycholate (NaDC) is known to cause disaggregation of AmB and to form monomers,
      as is observed by the increase of absorbance at 414 nm. By following the
      fluorescence intensity at 472 nm (lambda(ex) 335 nm), it was found that with
      increasing NaDC concentration there is a progressive disaggregation of AmB
      leading to increase in both monomeric and dimeric forms. Although the presence of
      dimeric AmB form in NaDC micellar media is known, observation of the growth of
      the dimeric species is novel. Studies in fluorescence lifetime and steady state
      fluorescence anisotropy also support this conclusion. As NaDC (at ca. 10 mM) is
      the preferred choice of medium for AmB delivery and AmB aggregation has been
      implicated for its toxicity, the observation of dimeric AmB at these NaDC
      concentrations assumes significance.

PMID- 18725182
TI  - Nephrin and podocin loss is prevented by mycophenolate mofetil in early
      experimental diabetic nephropathy.
AB  - Several works in the setting of early experimental diabetic nephropathy using
      anti-inflammatory drugs, such as mycophenolate mofetil (MMF), have shown that
      prevention of the development or amelioration of renal injury including
      proteinuria. The exact mechanisms by which anti-inflammatory drugs lower the
      albuminuria have no still to clarify well. In this study, diabetes was induced by
      injection of streptozotocin after uninephrectomy. Rats were randomly divided into
      three groups: control group, diabetic group and diabetic group treated with MMF.
      Elevated 24h urinary albumin excretion rate was markedly attenuated by MMF
      treatment. In diabetic rats receiving no treatment, there were increase in ED-1+
      cells in the glomeruli, which were effectively suppressed by MMF treatment. The
      expression of nephrin and podocin protein was reduced in the glomeruli from
      diabetic rats, and MMF treatment significantly increased the expression of
      nephrin and podocin. The expression of IL-1, TNF-alpha and 3-NT protein in the
      glomeruli were significantly increased in diabetic rats, which were all
      significantly inhibited by MMF treatment. Our results show that MMF could
      decrease urinary albumin excretion, which mechanism may be at least partly
      correlated with upregulated expression of nephrin and podocin in the glomeruli of
      diabetic rat.

PMID- 18725183
TI  - Quantitative approach to ultrasonic emulsion separation.
AB  - Ultrasound of 2 MHz was irradiated to the emulsion prepared from canola oil and
      water and flocculation of the oil droplets occurred immediately. By putting the
      emulsion sample in a thin glass cell and setting it in bath type irradiation
      equipment, the progress of the separation was quantitatively monitored with the
      optical absorbance. The use of the cell enables visual observation of the
      behavior of oil droplets. Pictures show the formation of flocks of the dispersed
      phase and the appearance of checkered pattern consisting of flocks at a regular
      interval. The observation indicates that the action of radiation forces on oil
      droplets, which causes the flocculation. The flocks started to rise after
      stopping irradiation with holding their shape. The rising rate of the flocks was
      significantly greater than that of oil droplets in the original emulsion.
      Ultrasonic irradiation caused a rapid decrease in the absorbance, which expresses
      a progress of the separation. Effects of two major operation parameters, power
      and time on the separation degree were examined. The degree improved with
      increasing power input and irradiation time. The dataset was arranged in a plot
      of normalized separation degree against the input energy. The plot suggests that
      effective separation was attained with a lower power input and a longer
      irradiation time. The plot provides a guide for setting condition for the
      separation.

PMID- 18725184
TI  - A Q312X mutation in the hemojuvelin gene is associated with cardiomyopathy due to
      juvenile haemochromatosis.
AB  - BACKGROUND AND AIMS: Juvenile haemochromatosis (JH) is an autosomal recessive
      iron disorder characterized by the early onset of secondary cardiomyopathy. The
      candidate modifier genes are hemojuvelin (HJV) and hepcidin antimicrobial peptide
      (HAMP). In the Japanese population, the prevalence of JH is quite low. The
      influence of HJV mutation on the JH phenotype is still unclear. METHODS AND
      RESULTS: We searched for possible mutations in a Japanese family with 2 members
      who were JH patients with severe heart failure. To search for possible variants
      in the HJV and HAMP genes, we performed direct sequencing in the family members.
      A homozygous nonsense mutation in exon 4 of HJV (Q312X) was identified in the JH
      patients and their mother. Three individuals in the family were heterozygous for
      this mutation. Subsequently, we evaluated the frequency of Q312X mutation in a
      large population (n=361) without heart failure, using allele-specific real-time
      PCR assay. No Q312X mutation was detected in this population. In the patients
      with the homozygous HJV mutation, iron loading revealed high serum ferritin
      concentration with accompanying elevated transferrin iron saturation. In
      contrast, ferritin levels were within the normal range in individuals with the
      heterozygous mutation. CONCLUSIONS: We found a nonsense mutation in the HJV gene.
      This mutation elevates ferritin levels and leads to JH associated with severe
      cardiomyopathy.

PMID- 18725185
TI  - Clinical efficacy of dim light melatonin onset testing in diagnosing delayed
      sleep phase syndrome.
AB  - BACKGROUND: Delayed Sleep Phase Syndrome (DSPS) arises from biological clock
      desynchrony and accounts for 10% of chronic insomnia patients. Currently DSPS is
      diagnosed based on sleep/wake cycle disruptions rather than examining the
      underlying biological clock alterations. The objective of the study was to
      determine the sensitivity and specificity of the Dim Light Melatonin Onset (DLMO)
      Test in diagnosing DSPS in a clinical setting. METHODS: Fifty-six patients (mean
      age 28 years) symptomatic of DSPS participated in the study. Following an initial
      assessment of DSPS using sleep diaries, participants underwent two consecutive
      nights of polysomnography (PSG), with an imposed sleep period on the second night
      to demonstrate the delay in the timing of habitual sleep period and to thereby
      confirm DSPS. Circadian phase delays were also measured using melatonin secretion
      profiles, and the efficacy of diagnosing DSPS using DLMO was compared to using
      sleep diaries and PSG. Melatonin secretion was assayed for each individual by
      ELISA using saliva samples. RESULTS: Main outcome measures included the time of
      melatonin secretion onset, clinical sensitivity and specificity of the DLMO test.
      The time of melatonin secretion onset was significantly delayed in DSPS patients.
      Clinical sensitivity and specificity of the DLMO test in diagnosing DSPS were
      90.3% and 84.0%, respectively. CONCLUSIONS: The DLMO test is an accurate tool for
      differentiating between sleep disorder patients with or without underlying
      circadian rhythm disruption. It is effective for phase typing DSPS patients in a
      clinical setting.

PMID- 18725186
TI  - Hypothalamic mechanisms coordinating cardiorespiratory function during exercise
      and defensive behaviour.
AB  - Defensive behaviour evoked by mild or moderate psychological stress as well as
      increased activity and arousal are part of everyday life in humans and other
      animals. Both defensive behaviour and exercise are associated with marked and
      often quite stereotyped changes in autonomic and respiratory function. These
      patterned responses are generated by feed-forward or "central command"
      mechanisms, and are also modulated by feedback from peripheral receptors. In this
      review we first describe the pattern of autonomic and respiratory changes
      associated with defensive behaviour and exercise, and then discuss the central
      mechanisms that generate these patterned responses in the light of recent
      studies, with a particular focus on the role of the dorsomedial hypothalamus
      (DMH). We consider the hypothesis that the cardiorespiratory changes associated
      with defensive behaviour and exercise may, at least in part, be driven by common
      central mechanisms. Finally, we discuss the possible role of the DMH in
      generating circadian rhythms in arterial blood pressure and heart rate, and also
      in generating longer-term increases in sympathetic activity in some types of
      hypertension.

PMID- 18725187
TI  - On scaffold designing for bone regeneration: A computational multiscale approach.
AB  - Scaffold design for bone tissue engineering applications involves many parameters
      that directly influence the rate of bone tissue regeneration onto its
      microstructural surface. To improve scaffold functionality, increasing interest
      is being focused on in vitro and in vivo research in order to obtain the optimal
      scaffold design for a specific application. However, the evaluation of the effect
      of each specific scaffold parameter on tissue regeneration using these techniques
      requires costly protocols and long-term experiments. In this paper, we elucidate
      the effect of some scaffold parameters on bone tissue regeneration by means of a
      mathematically based approach. By virtue of in silico experiments, factors such
      as scaffold stiffness, porosity, resorption kinetics, pore size and pre-seeding
      are analyzed in a specific bone tissue application found in the literature. The
      model predicts the in vivo rate of bone formation within the scaffold, the
      scaffold degradation and the interaction between the implanted scaffold and the
      surrounding bone. Results show an increasing rate of bone regeneration with
      increasing scaffold stiffness, scaffold mean pore size and pre-seeding, whereas
      the collapse of the scaffold occurs for a faster biomaterial resorption kinetics.
      Requiring further experimental validation, the model can be useful for the
      assessment of scaffold design and for the analysis of scaffold parameters in
      tissue regeneration.

PMID- 18725188
TI  - Presence of corrosion products and hypersensitivity-associated reactions in
      periprosthetic tissue after aseptic loosening of total hip replacements with
      metal bearing surfaces.
AB  - Aseptic loosening of articular implants is frequently associated with tissue
      reactions to wear particles. Some patients, who had received metal-on-metal
      articulations, present early symptoms including persistent pain and implant
      failure. These symptoms raise the suspicion about the development of an
      immunological response. Furthermore, the generation of rare corrosion products in
      association with metallic implants has been observed. Corrosion products are
      known to enhance third-body wear and contribute to the loss of the implant. The
      purpose of this study was to investigate periprosthetic tissue containing solid
      corrosion products after aseptic loosening of second-generation metal-on-metal
      total hip replacements made of low-carbon cobalt-chromium-molybdenum alloy for
      the presence of immunologically determined tissue changes. Periprosthetic tissue
      of 11 cases containing uncommon solid deposits was investigated by light
      microscopy. In order to confirm the presence of corrosion products, additional
      methods including scanning electron microscopy (SEM) investigation, energy
      dispersive X-ray (EDX) and Fourier transform infrared microspectroscopy (FTIR)
      analysis were used. All investigated cases revealed solid chromium orthophosphate
      corrosion products as well as metallic wear particles to a various extent.
      Moreover, various intense tissue reactions characteristic of immune response were
      observed in all cases. The simultaneous presence of corrosion products and
      hypersensitivity-associated tissue reaction indicates that a relationship between
      corrosion development and implant-related hypersensitivity may exist.

PMID- 18725189
TI  - A peptide containing residues 26-44 of tau protein impairs mitochondrial
      oxidative phosphorylation acting at the level of the adenine nucleotide
      translocator.
AB  - Having confirmed that adenovirus-mediated overexpression of NH(2)-tau fragment
      lacking the first 25 aminoacids evokes a potent neurotoxic effect, sustained by
      protracted stimulation of NMDA receptors, in primary neuronal cultures we
      investigated whether and how chemically synthesized NH(2)-derived tau peptides,
      i.e. NH(2)-26-44 and NH(2)-1-25 fragments, affect mitochondrial function. We
      tested both fragments on each step of the processes leading to ATP synthesis via
      oxidative phosphorylation: i) electron flow via the respiratory chain from
      physiological substrates to oxygen with the activity of each individual complex
      of the respiratory chain investigated in some detail, ii) membrane potential
      generation arising from externally added succinate and iii) the activity of both
      the adenine nucleotide translocator and iv) ATP synthase. Oxidative
      phosphorylation is not affected by NH(2)-1-25 tau fragment, but dramatically
      impaired by NH(2)-26-44 tau fragment. Both cytochrome c oxidase and the adenine
      nucleotide translocator are targets of NH(2)-26-44 tau fragment, but adenine
      nucleotide translocator is the unique mitochondrial target responsible for
      impairment of oxidative phosphorylation by the NH(2)-26-44 tau fragment, which
      then exerts deleterious effects on cellular availability of ATP synthesized into
      mitochondria.

PMID- 18725191
TI  - Molecular organization of 2-(2,4-dihydroxylphenyl)-5,6-dichlor 1,3-benzothiazole
      in monomolecular layers formed with diphytanoylphosphatidylcholine: a linear
      dichroism-FTIR study.
AB  - 2-(2,4-Dihydroxylphenyl)-5,6-dichlor 1,3-benzothiazole (dHBBT) has very strong
      antifungal and antitumoral properties in relation to human cancer cells. The aim
      of this research was to analyze the binding process of dHBBT molecules to the
      lipid membrane formed from DPhPC at the air-water interface. The effect of dHBBT
      on the organization of lipid membranes formed with diphytanoylphosphatidylcholine
      (DPhPC) was studied with the application of monomolecular layer technique, FTIR
      spectroscopy and linear dichroism-FTIR. On the basis of linear dichroism
      experiments the mean orientation angle theta between the molecular axis and the
      normal to monolayer surface was determined. Mean value was calculated at theta=72
      degrees and indicates a horizontal orientation of dHBBT molecules in the lipid
      membrane formed from DPhPC. dHBBT molecules have considerable influence on the
      orientation of DPhPC acyl chains. The mean value of the angle between normal to
      monolayer surface and the main axis of the acyl chain is approximately 45 degrees
      for DPhPC, while for the lipid monolayer containing dHBBT it is approximately 18
      degrees. Such extreme changes in orientation of acyl chains indicate a clear
      influence of the relationship on the dynamic and structural properties of the
      monolayer formed from DPhPC. Biological activity of dHBBT molecules is tightly
      associated with its molecular organization. The results of the research presented
      in this work are potentially valuable in respect of the development of
      pharmacologically active preparations of dHBBT.

PMID- 18725190
TI  - Amyloid-beta peptide induces temporal membrane biphasic changes in astrocytes
      through cytosolic phospholipase A2.
AB  - Oligomeric amyloid-beta peptide (Abeta) is known to induce cytotoxic effects and
      to damage cell functions in Alzheimer's disease. However, mechanisms underlying
      the effects of Abeta on cell membranes have yet to be fully elucidated. In this
      study, Abeta 1-42 (Abeta(42)) was shown to cause a temporal biphasic change in
      membranes of astrocytic DITNC cells using fluorescence microscopy of Laurdan.
      Abeta(42) made astrocyte membranes became more molecularly-disordered within the
      first 30 min to 1 h, but gradually changed to more molecularly-ordered after 3 h.
      However, Abeta(42) caused artificial membranes of vesicles made of rat whole
      brain lipid extract to become more disordered only. The trend for more
      molecularly-ordered membranes in astrocytes induced by Abeta(42) was abrogated by
      either an NADPH oxidase inhibitor, apocynin, or an inhibitor of cytosolic
      phospholipase A(2) (cPLA(2)), but not by an inhibitor of calcium-independent
      PLA(2) (iPLA(2)). Apocynin also suppressed the increased production of superoxide
      anions (O(2)(-)) and phosphorylation of cPLA(2) induced by Abeta(42). In
      addition, hydrolyzed products of cPLA(2), arachidonic acid (AA), but not
      lysophosphatidylcholine (LPC) caused astrocyte membranes to become more
      molecularly-ordered. These results suggest (1) a direct interaction of Abeta(42)
      with cell membranes making them more molecularly-disordered, and (2) Abeta(42)
      also indirectly makes membranes become more molecularly-ordered by triggering the
      signaling pathway involving NADPH oxidase and cPLA(2) in astrocytes.

PMID- 18725193
TI  - Fine epitope mapping of humanized anti-IgE monoclonal antibody omalizumab.
AB  - Omalizumab is a humanized anti-IgE antibody that inhibits IgE binding to its
      receptors on mast cells and basophils, thus blocking the IgE-mediated release of
      pharmacologic mediators from these cells. Previous studies have indicated that
      omalizumab binds to the Cepsilon3 domain of IgE, which is the binding site of IgE
      receptors, but the precise epitope recognized by omalizumab is unknown. In this
      study, we employed the phage display peptide library technology to select
      peptides binding to omalizumab. A striking peptide sequence motif was recovered,
      which is homologous to the sequence (424)HLP(426) within the Cepsilon3 domain of
      IgE-Fc. Our results further indicated that omalizumab specifically bound to the
      synthesized peptide "(421)THPHLPRALMRS(432)" containing the (424)HLP(426) motif
      in IgE-Fc. We therefore conclude that the (424)HLP(426) motif is the omalizumab
      epitope. This epitope overlaps with the high-affinity IgE receptor-binding site,
      thus providing insights into the structural basis for the mechanism of action of
      omalizumab.

PMID- 18725192
TI  - Molecular cloning, expression, and characterization of a novel endo-alpha-N
      acetylgalactosaminidase from Enterococcus faecalis.
AB  - We report here the molecular cloning, expression and characterization of a novel
      endo-alpha-N-acetylgalactosaminidase, classified into the GH101 family, from
      Enterococcus faecalis (endo-EF). The recombinant endo-EF was found to catalyze
      the liberation of core1-disaccharides (Galbeta1-3GalNAc) from core1-pNP (Galbeta1
      3GalNAcalpha-pNP) like other GH101 family enzymes. However, endo-EF seems to
      differ in specificity from the GH101 enzymes reported to date, because it was
      able to release trisaccharides from core2-pNP (Galbeta1-3[GlcNAcbeta1
      6]GalNAcalpha-pNP) and tetrasaccharides from Gal-core2-pNP (Galbeta1-3[Galbeta1
      3GlcNAcbeta1-6]GalNAcalpha-pNP). Interestingly, the enzyme could transfer not
      only core1-disaccharides but also core2-trisaccharides to alkanols generating
      alkyl-oligosaccharides. Endo-EF should facilitate O-glycoprotein research.

PMID- 18725194
TI  - Thermodynamic analysis of the heterodimerization of leucine zippers of Jun and
      Fos transcription factors.
AB  - Jun and Fos are components of the AP1 family of transcription factors and bind to
      the promoters of a diverse multitude of genes involved in critical cellular
      responses such as cell growth and proliferation, cell cycle regulation, embryonic
      development and cancer. Here, using the powerful technique of isothermal
      titration calorimetry, we characterize the thermodynamics of heterodimerization
      of leucine zippers of Jun and Fos. Our data suggest that the heterodimerization
      of leucine zippers is driven by enthalpic forces with unfavorable entropy change
      at physiological temperatures. Furthermore, the basic regions appear to modulate
      the heterodimerization of leucine zippers and may undergo at least partial
      folding upon heterodimerization. Large negative heat capacity changes
      accompanying the heterodimerization of leucine zippers are consistent with the
      view that leucine zippers do not retain alpha-helical conformations in isolation
      and that the formation of the native coiled-coil alpha-helical dimer is attained
      through a coupled folding-dimerization mechanism.

PMID- 18725195
TI  - Up-regulation of E-cadherin by small activating RNA inhibits cell invasion and
      migration in 5637 human bladder cancer cells.
AB  - Recent studies have reported that chemically synthesized small duplex RNAs
      complementary to promoters of target genes can specifically induce gene
      expression in several cancer cell lines. Such dsRNA, referred to as small
      activating RNA (saRNA), are involved in the recently described phenomenon called
      RNA activation (RNAa). Recent findings show that saRNA can inhibit cell
      proliferation and viability via up-regulation of p21(WAF1/CIP1) (p21) in human
      bladder cancer cells. In the present study, we demonstrate that induction of E
      cadherin expression by saRNA leads to suppression of migration and invasion of
      5637 human bladder cancer cells in vitro. The elevated E-cadherin expression was
      confirmed at transcriptional and protein levels after transfection of a 21
      nucleotide dsRNA targeting the E-cadherin promoter (dsEcad). Furthermore, this
      inhibitory effect was associated with relocalization of beta-catenin from the
      nucleus to the plasma membrane and decreased beta-catenin-mediated
      transactivation. These data suggest that activation of E-cadherin by saRNA may
      have a therapeutic benefit for bladder and other types of cancer.

PMID- 18725196
TI  - VIP induces PKA-mediated rapid and sustained phosphorylation of HSP20.
AB  - The small molecular weight heat shock protein HSP20 has been proposed to regulate
      smooth muscle relaxation in a manner dependent on its phosphorylated state. We
      present the first evidence of HSP20 phosphorylation in response to a naturally
      occurring neurotransmitter. HSP20 was rapidly phosphorylated in colonic circular
      smooth muscle cells exposed to the physiologically relevant relaxant
      neuropeptide, Vasoactive Intestinal Peptide (VIP). HSP20 phosphorylation was
      significantly and substantially increased by 30s following VIP treatment and
      remained elevated for 30 min. VIP-induced HSP20 phosphorylation was dose
      dependent. Both basal and VIP-induced HSP20 phosphorylations were solely mediated
      by Protein Kinase A. Maximal phosphorylation of HSP20 was induced by the same VIP
      concentration range which induces maximal relaxation. Increased phosphorylation
      of HSP20 occurred in both cytosolic and particulate cell fractions. Our findings
      represent evidence for neurogenic modulation of the cyclic molecular regulation
      of relaxation required for peristalsis via a VIP-PKA-HSP20 pathway.

PMID- 18725197
TI  - Development and precise characterization of phospho-site-specific antibody of
      Ser(357) of IRS-1: elimination of cross reactivity with adjacent Ser(358).
AB  - Antibodies that recognize specifically phosphorylated sites on proteins are
      widely utilized for studying the regulation and biological function of
      phosphoproteins. The proposed strategy is a powerful, analytical tool allowing
      the generation of phospho-site specific antibodies albeit adjacent
      phosphorylation sites are present. Here, we demonstrate the assessment and
      elimination of cross reactivity of phospho-site-specific-Ser(357) IRS-1 antibody.
      While determining the specificity of p-Ser(357) antiserum we came across the
      cross reactivity of the antiserum with adjacent Ser(358) which was successfully
      abolished by an improved immuno-purification method. The specificity of the
      purified antiserum was then verified by indirect ELISA, results of ELISA were
      also mirrored in the experiments carried out in BHK-IR cells using different
      mutants of IRS-1 carrying mutations at either Ser(357)/Ser(358)/Ser(357/358).
      Immuno-purified-p-Ser(357) did not react with IRS-1 Ala(357) and IRS-1
      Ala(357/358). In conclusion, the present study describes generation and
      characterization of p-Ser(357) IRS-1 antibody, which reacts with IRS-1 in site
      specific and phosphorylation state-dependent manner without showing cross
      reactivity to adjacent Ser(358). This antibody can be effectively used to further
      clarify the inhibitory role of Ser(357) in insulin signal transduction.

PMID- 18725198
TI  - Cell shape regulation by Gravin requires N-terminal membrane effector domains.
AB  - Gravin (AKAP12, SSeCKS) is a scaffolding protein that acts as a potent inhibitor
      of tumor metastasis in vivo and in vitro, and regulates morphogenesis during
      vertebrate gastrulation. Despite being implicated in many cellular processes,
      surprisingly little is known about the mechanism by which Gravin elicits cell
      shape changes. In this work, we use in vitro cell spreading assays to demonstrate
      that the Gravin N-terminus containing the three MARCKS-like basic regions (BRs)
      is necessary and sufficient to regulate cell shape in vitro. We show that the
      conserved phosphorylation sites in the BRs are essential for their function in
      these assays. We further demonstrate that the Gravin BRs are necessary for in
      vivo function during gastrulation in zebrafish. Together, these results provide
      an important step forward in understanding the mechanism of Gravin function in
      cell shape regulation and provide valuable insight into how Gravin acts as a
      cytoskeletal regulator.

PMID- 18725200
TI  - Arabidopsis AAL-toxin-resistant mutant atr1 shows enhanced tolerance to
      programmed cell death induced by reactive oxygen species.
AB  - The fungal AAL-toxin triggers programmed cell death (PCD) through perturbations
      of sphingolipid metabolism in AAL-toxin-sensitive plants. While Arabidopsis is
      relatively insensitive to the toxin, the loh2 mutant exhibits increased
      susceptibility to AAL-toxin due to the knockout of a gene involved in
      sphingolipid metabolism. Genetic screening of mutagenized loh2 seeds resulted in
      the isolation of AAL-toxin-resistant mutant atr1.Atr1 displays a wild type
      phenotype when grown on soil but it develops less biomass than loh2 on media
      supplemented with 2% and 3% sucrose. Atr1 was also more tolerant to the reactive
      oxygen species-generating herbicides aminotriazole (AT) and paraquat. Microarray
      analyses of atr1 and loh2 under AT-treatment conditions that trigger cell death
      in loh2 and no visible damage in atr1 revealed genes specifically regulated in
      atr1 or loh2. In addition, most of the genes strongly downregulated in both
      mutants were related to cell wall extension and cell growth, consistent with the
      apparent and similar AT-induced cessation of growth in both mutants. This
      indicates that two different pathways, a first controlling growth inhibition and
      a second triggering cell death, are associated with AT-induced oxidative stress.

PMID- 18725199
TI  - Molecular cloning, expression, and characterization of mouse amine N
      sulfotransferases.
AB  - By searching the GenBank database, we recently identified a novel mouse cytosolic
      sulfotransferase (SULT) cDNA (IMAGE Clone ID 679629) and a novel mouse SULT gene
      (LOC 215895). Sequence analysis revealed that both mouse SULTs belong to the
      cytosolic SULT3 gene family. The recombinant form of these two newly identified
      SULTs, designated SULT3A1 and SULT3A2, were expressed using the pGEX-4T-1
      glutathione S-transferase fusion system and purified from transformed BL21
      Escherichia coli cells. Both purified SULT3A1 and SULT3A2 exhibited strong amine
      N-sulfonating activities toward 1-naphthylamine among a variety of endogenous and
      xenobiotic compounds tested as substrates. Kinetic constants of the sulfation of
      1-naphthylamine and 1-naphthol by these two enzymes were determined.
      Collectively, these results imply that these two amine-sulfonating SULT3s may
      play essential roles in the metabolism and detoxification of aromatic amine
      compounds in the body.

PMID- 18725201
TI  - In vitro differentiation of human adipose tissue-derived stem cells into cells
      with pancreatic phenotype by regenerating pancreas extract.
AB  - Pancreas extract from regenerating pancreas after partial pancreatectomy is known
      to contain factors that induce islet neogenesis in animals with streptozotocin
      (STZ)-induced diabetes [A.A. Hardikar, R.R. Bhonde, Modulating experimental
      diabetes by treatment with cytosolic extract from the regenerating pancreas,
      Diabetes Res. Clin. Pract. 46 (1999) 203-211]. In this study, we evaluate the
      effects of regenerating pancreas extract (RPE) from 90% partially
      pancreatectomized rats on induction of pancreatic differentiation of human
      adipose tissue-derived stem cells (hASCs). We found that undifferentiated hASCs
      expressed OCT-3/4, Nanog, and REX-1, markers of embryonic stem cells (ESCs).
      Genes involved in early pancreas development showed increased expression in RPE
      treated culture. Sox17 and IPF-1 were expressed only in RPE-treated culture.
      Immunocytochemical analysis showed C-peptide-positive cells in RPE-treated
      culture but not in undifferentiated hASCs. In conclusion, hASCs have the
      characteristics of ESCs and the potential to differentiate into pancreas cell
      lineages phenotypically in response to RPE.

PMID- 18725202
TI  - The significance of disulfide bonding in biological activity of HB-EGF, a
      mutagenesis approach.
AB  - A site-directed mutagenesis approach was taken to disrupt each of 3 disulfide
      bonds within human HB-EGF by substituting serine for both cysteine residues that
      contribute to disulfide bonding. Each HB-EGF disulfide analogue (HB-EGF
      Cys/Ser(108/121), HB-EGF-Cys/Ser(116/132), and HB-EGF-Cys/Ser(134/143)) was
      cloned under the regulation of the mouse metallothionein (MT) promoter and stably
      expressed in mouse fibroblasts. HB-EGF immunoreactive proteins with M(r) of 6.5,
      21 and 24 kDa were observed from lysates of HB-EGF and each HB-EGF disulfide
      analogue. HB-EGF immunohistochemical analyses of each HB-EGF stable cell line
      demonstrated ubiquitous protein expression except HB-EGF-Cys/Ser(108/121) and HB
      EGF-Cys/Ser(116/132) stable cell lines which exhibited accumulated expression
      immediately outside the nucleus. rHB-EGF, HB-EGF, and HB-EGF(134/143) proteins
      competed with 125I-EGF in an A431 competitive binding assay, whereas HB-EGF
      Cys/Ser(108/121) and HB-EGF-Cys/Ser(116/132) failed to compete. Each HB-EGF
      disulfide analogue lacked the ability to stimulate tyrosine phosphorylation of
      the 170 kDa EGFR. These results suggest that HB-EGF-Cys/Ser(134/143) antagonizes
      EGFRs.

PMID- 18725203
TI  - An abnormal pK(a) value of internal histidine of the insulin molecule revealed by
      neutron crystallographic analysis.
AB  - Insulin is stored in pancreatic beta-cell as hexameric form with Zn2+ ions, while
      the hormonally active form is monomer. The hexamer requires the coordination of
      Zn2+ ions to the HisB10. In order to reveal the mechanism of the hexamerization
      of insulin, we investigated the Zn2+ free insulin at pD6.6 and pD9 by neutron
      crystallographic analyses. HisB10 is doubly protonated not only at pD6.6 but also
      at pD9, indicating an abnormal pK(a) of this histidine. It is suggested that
      HisB10 acts on a strong cation capture and contributes to the high stability of
      the hexameric form in pancreas.

PMID- 18725204
TI  - Cloning and functional analysis of novel short-chain cis-prenyltransferases.
AB  - cis-Prenyltransferase catalyzes the synthesis of Z,E-mixed prenyl diphosphates by
      sequential condensation of isopentenyl diphosphate with allylic diphosphate. cis
      Prenyltransferases can be classified into three subgroups: short-, medium-, and
      long-chain cis-prenyltransferase, according to their product chain lengths. cis
      Farnesyl diphosphate synthase from Mycobacterium tuberculosis has been the only
      example as short-chain cis-prenyltransferase so far characterized. In this study,
      we cloned the novel short-chain cis-prenyltransferases from three different
      bacteria, and characterized their enzymatic activities to compare and elucidate a
      common feature of the short-chain cis-prenyltransferases. Furthermore, we
      identified a specific isoleucine that is conserved in short-chain cis
      prenyltransferases and located in close proximity of the omega-end of the geranyl
      diphosphate. Several site-directed mutants with respect to the isoleucine residue
      synthesized longer prenyl chain products and showed broader allylic substrate
      specificity. These results suggested that the isoleucine plays an important role
      in the substrate specificity and chain length determination mechanism of cis
      prenyltransferase.

PMID- 18725205
TI  - Caveolin-1 regulates BMPRII localization and signaling in vascular smooth muscle
      cells.
AB  - Recent studies demonstrate the interaction of BMPRII and caveolin-1 in various
      cell types. In this study we test the hypothesis that caveolin-1 interacts with
      and regulates BMPRII-dependent signaling in vascular smooth muscle cells. We
      demonstrate that BMPRII localizes to caveolae and directly interacts with
      caveolin-1 in mouse aortic smooth muscle cells. We demonstrate that this
      interaction is mediated by the caveolin-1 scaffolding domain and is regulated by
      caveolin-1 phosphorylation. Downregulation of caveolin-1 via siRNA resulted in a
      loss of BMP-dependent SMAD phosphorylation and gene regulation. Further studies
      revealed that loss of caveolin-1 results in decreased BMPRII membrane
      localization and decreased association of BMPRII with the type I BMP receptor
      BMPRIa. Dominant negative caveolin-1 decreased BMPRII membrane localization
      suggesting a role for caveolin-1 in BMPRII trafficking. Taken together, our
      findings establish caveolin-1 as an important regulator of downstream signaling
      and membrane targeting of BMPRII in vascular smooth muscle cells.

PMID- 18725206
TI  - Immunotherapy of hepatocellular carcinoma with a vaccine based on xenogeneic
      homologous alpha fetoprotein in mice.
AB  - alpha-Fetoprotein (AFP) is a diagnostic marker for the presence of hepatocellular
      carcinoma, and a potential target for immunotherapy. Unfortunately, the immunity
      to AFP is presumably difficult to elicit because of immune tolerance acquired
      during the development of immune system. In the present study, we used AFP as a
      model antigen to explore the feasibility of the immunotherapy of AFP-positive
      liver cancer by the breaking of immune tolerance against AFP in a cross-reaction
      between the xenogeneic homologues and self molecules. Recombinant rat AFP was
      prepared as a vaccine, and mouse AFP was prepared as a control. Immunized with
      rat AFP was effective at protective and therapeutic antitumor immunity in
      hepatocellular carcinoma model in mice. Both humoral and cellular immune
      responses may be responsible for the antitumor activity against AFP-positive
      tumor cells, and no marked side effects were observed in the immunized mice.
      Thus, our study may provide an effective vaccine strategy for the treatment of
      AFP-positive hepatocellular carcinoma, and may be of importance to further
      exploration of the breaking of immune tolerance to self molecules.

PMID- 18725207
TI  - Age- and sex-dependent expression of multiple murine hepatic hydroxysteroid
      sulfotransferase (SULT2A) genes.
AB  - Hydroxysteroid sulfotransferase (SULT2A) enzymes play important roles in hepatic
      steroid and xenobiotic metabolism. Unlike humans, which express one SULT2A,
      inspection of mouse genome information indicated the presence of seven SULT2A
      genes within a cluster on chromosome 7. The age- and sex-dependent expressions of
      the seven murine SULT2A family members were characterized in the livers of
      C57BL/6 mice using real-time RT-PCR. The transcripts for three of the SULT2A
      forms (NCBI reference/model sequences XM_001471624, NM_009286 and NM_001111296)
      were abundant in pre-pubertal male and female mouse liver but were essentially
      silenced in the livers of adult male mice. The mRNAs of three other SULT2A forms
      (NM_001101534, XM_894052 and NM_001081325) were also expressed in pre-pubertal
      male and female mouse liver, but at markedly reduced levels relative to those of
      the abundant forms. The mRNA levels of these lower-abundance forms were further
      suppressed in adult animals. A seventh SULT2A mRNA (XM_983034) was expressed in
      adult male and female mouse liver, but was not detected in pre-pubertal mouse
      liver of either sex. Full-length amplifications with primers targeting
      untranslated regions confirmed that all SULT2A forms were expressed. However,
      while the XM_001471624, NM_001111296, NM_001101534, XM_894052 and NM_001081325
      transcripts were detected at their predicted sizes, the NM_009286 and XM_983034
      transcripts each lacked two predicted exons. These results demonstrate that seven
      murine SULT2As display different profiles of age- and sex-dependent hepatic
      expression.

PMID- 18725208
TI  - A novel approach to non-biased systematic random sampling: a stereologic estimate
      of Purkinje cells in the human cerebellum.
AB  - Non-biased systematic sampling using the principles of stereology provides
      accurate quantitative estimates of objects within neuroanatomic structures.
      However, the basic principles of stereology are not optimally suited for counting
      objects that selectively exist within a limited but complex and convoluted
      portion of the sample, such as occurs when counting cerebellar Purkinje cells. In
      an effort to quantify Purkinje cells in association with certain
      neurodegenerative disorders, we developed a new method for stereologic sampling
      of the cerebellar cortex, involving calculating the volume of the cerebellar
      tissues, identifying and isolating the Purkinje cell layer and using this
      information to extrapolate non-biased systematic sampling data to estimate the
      total number of Purkinje cells in the tissues. Using this approach, we counted
      Purkinje cells in the right cerebella of four human male control specimens, aged
      41, 67, 70 and 84 years, and estimated the total Purkinje cell number for the
      four entire cerebella to be 27.03, 19.74, 20.44 and 22.03 million cells,
      respectively. The precision of the method is seen when comparing the density of
      the cells within the tissue: 266,274, 173,166, 167,603 and 183,575 cells/cm3,
      respectively. Prior literature documents Purkinje cell counts ranging from 14.8
      to 30.5 million cells. These data demonstrate the accuracy of our approach. Our
      novel approach, which offers an improvement over previous methodologies, is of
      value for quantitative work of this nature. This approach could be applied to
      morphometric studies of other similarly complex tissues as well.

PMID- 18725209
TI  - Effects of endothelial NOS antagonism within the periaqueductal gray on
      cardiovascular responses and neurotransmission during mechanical, heat, and cold
      nociception.
AB  - Nitric oxide (NO) is synthesized from L-arginine using NO synthase (NOS) enzyme
      that exists as 3 isoforms: endothelial (eNOS), neuronal (nNOS), and inducible
      (iNOS). We examined the role of eNOS within the dorsolateral periaqueductal gray
      mater (dlPAG) on cardiovascular responses along with glutamate and GABA
      concentrations during mechanical-, heat-, and cold-induced nociception in
      anesthetized rats. Mechanical stimulus was applied by a 10-second hindpaw pinch
      that increased mean arterial pressure (MAP) and heart rate (HR). Bilateral
      microdialysis of a selective eNOS antagonist, L-N(5)-(1-iminoethyl)ornithine (L
      NIO; 10 microM), into the dlPAG had no effect on MAP or HR during a mechanical
      stimulation. Heat stimulus was generated by immersing a hindpaw metatarsus in a
      water-bath at 52 degrees C for 10 s which increased glutamate, GABA, MAP and HR.
      Administration of L-NIO into the dlPAG augmented cardiovascular responses and
      glutamate increase, but attenuated GABA changes during the heat stimulus. In
      contrast, application of a cold stimulus by immersing the hindpaw at 10 degrees C
      for 10 s resulted in decreases in MAP, HR, and glutamate. However, there was an
      increase in GABA concentration. Following microdialysis of L-NIO into the dlPAG,
      the responses to the cold stimulus was reversed i.e., the cold stimulus induced
      pressor and tachycardic responses, augmented glutamate, and attenuated GABA
      levels. These results demonstrate that eNOS within the dlPAG plays a differential
      role on the cardiovascular system during heat- and cold-mediated nociception via
      modulating glutamatergic/GABAergic neurotransmission. However, the mechanical
      stimulation had no effect on cardiovascular responses following eNOS antagonism
      within the dlPAG.

PMID- 18725210
TI  - Antioxidants prevent the cytotoxicity of manganese in RBE4 cells.
AB  - Manganese (Mn) is an essential trace element required for ubiquitous enzymatic
      reactions. Chronic overexposure to this metal may, however, promote potent
      neurotoxic effects. The mechanism of Mn toxicity is not well established, but
      several studies indicate that oxidative stress and mitochondria play major roles
      in the Mn-induced neurodegenerative processes that lead to dysfunction in the
      basal ganglia. The aim of this study was to address the toxic effects of MnCl2
      and MnSO4 on the immortalized rat brain microvessel endothelial cell line (RBE4)
      and to characterize toxic mechanism associated with exposure to Mn. The
      cytotoxicity of Mn in RBE4 cells was evaluated using the LDH and the MTT assays.
      A significant increase was noted in LDH release from RBE4 cells exposed for 24 h
      to MnCl2 at concentrations of 800 microM and MnSO4 at concentrations > or = 400
      microM (p < 0.05) when compared with control unexposed cells. The MTT assay
      established significant decrease in cellular viability upon exposure to MnCl2 at
      concentrations > or = 100 microM and to MnSO4 at concentrations > or = 50 microM
      (p < 0.05). Thus, the cytotoxicity assays showed that the MTT assay was more
      sensitive than the LDH assay, suggesting that mitochondrial changes precede other
      toxic effects of Mn. In addition, upon exposure to MnCl2 (200 and 800 microM),
      intracellular reduced glutathione (GSH) levels in RBE4 cells decreased as Mn
      exposure concentrations increased (p < 0.05). To confirm the oxidative hypothesis
      of Mn cytotoxicity, co-exposure of MnCl2 with antioxidant agents (N
      acetylcysteine [NAC] or Trolox) were carried out. The cellular viability was
      evaluated using the MTT assay. A significant decrease in Mn cytotoxicity was
      observed in co-exposed cells confirming that (1) oxidative stress plays a
      critical role in the mechanism of Mn toxicity, and (2) antioxidants may offer a
      useful therapeutic modality to reverse the aberrant effects of Mn.

PMID- 18725211
TI  - Prevention of axonal injury using calpain inhibitor in chronic progressive
      experimental autoimmune encephalomyelitis.
AB  - Axonal injury is the major correlate of permanent disability in neurodegenerative
      diseases such as multiple sclerosis (MS), especially in secondary-progressive MS
      which follows relapsing-remitting disease course. Proteolytic enzyme, calpain, is
      a potential candidate for causing axonal injury. Most current treatment options
      only target the inflammatory component of MS. Previous work using calpain
      inhibitor CYLA in our laboratory showed significant reduction in clinical sign,
      demyelination and tissue calpain content in acute experimental autoimmune
      encephalomyelitis (EAE). Here we evaluated markers of axonal injury (amyloid
      precursor protein, Na(v)1.6 channels), neuronal calpain content and the effect of
      CYLA on axonal protection using histological methods in chronic EAE [myelin
      oligodendrocyte glycoprotein (MOG)-induced disease model of MS]. Intraperitoneal
      application of CYLA (2 mg/mouse/day) significantly reduced the clinical signs,
      tissue calpain content, demyelination and inflammatory infiltration of EAE.
      Similarly, markers for axonal injury were barely detectable in the treated mice.
      Thus, this novel drug, which markedly suppresses the disease course, axonal
      injury and its progression, is a candidate for the treatment of a
      neurodegenerative disease such as multiple sclerosis.

PMID- 18725212
TI  - VEGF increases blood-brain barrier permeability to Evans blue dye and tetanus
      toxin fragment C but not adeno-associated virus in ALS mice.
AB  - Entry of most compounds into the CNS is impeded by the blood-brain barrier (BBB).
      Because vascular endothelial growth factor (VEGF) is important in the formation
      and maintenance of the BBB and is known to modulate BBB permeability in newborn
      rodents, we tested the hypothesis that VEGF may enhance BBB permeability in adult
      mice. We examined the effect of VEGF on the CNS distribution of three different
      agents: a small molecule (Evans blue dye) that is known to bind plasma proteins,
      an exogenous protein (tetanus toxin fragment C; TTC), and a viral vector
      (recombinant adeno-associated virus serotype 2/5 marked with lacZ; rAAV2/5-lacZ).
      Pretreatment with VEGF (20 mug; i.v.) increased permeability of the BBB to Evans
      blue dye and TTC as detected by augmented concentrations of these substances in
      the cerebrum, brainstem, and spinal cord. By contrast, VEGF did not alter BBB
      permeability to AAV2/5-lacZ, as defined by beta-galactosidase activity assay.
      These data demonstrate the potential utility of VEGF for pharmacological
      modulation of the BBB, and indicate that the increase in BBB permeability
      mediated by VEGF is limited by the size of the delivered substance.

PMID- 18725214
TI  - Anisomycin infusion in amygdala impairs consolidation of odor aversion memory.
AB  - Conditioned odor aversion (COA) results from the association between a novel odor
      and a delayed visceral illness. Basolateral amygdala is crucial for COA learning
      but its importance in COA consolidation remains to be demonstrated. We
      investigated whether infusion of anisomycin, a protein synthesis inhibitor, in
      the basolateral amygdala impaired COA consolidation. COA was greatly impaired
      when anisomycin was infused immediately before odor-malaise pairing, but not
      between odor and malaise. This suggests that the formation of odor
      representation, rather than malaise integration, within the amygdala has been
      disrupted. Anisomycin infusion before acquisition did not affect short-term
      memory (tested 4 h after odor-malaise pairing) but dramatically impaired long
      term COA memory (tested 3 days later). This indicates specific consolidation
      impairment. Control experiments indicated that anisomycin infusion did not affect
      amygdala functionality and olfactory perception and did not induce cell death in
      the amygdala. Moreover, anisomycin treatment induced an important decrease (65
      70%) of LiCl-induced Fos protein expression in the basolateral and the central
      nuclei of the amygdala but not in adjacent piriform cortex indicating a reliable
      and localized protein synthesis inhibition. These findings suggest the pivotal
      role of the basolateral amygdala, and possibly the central amygdala, in COA
      memory consolidation.

PMID- 18725213
TI  - Event-related fast optical signal in a rapid object recognition task: improving
      detection by the independent component analysis.
AB  - Noninvasive recording of fast optical signals presumably reflecting neuronal
      activity is a challenging task because of a relatively low signal-to-noise ratio.
      To improve detection of those signals in rapid object recognition tasks, we used
      the independent component analysis (ICA) to reduce "global interference"
      (heartbeat and contribution of superficial layers). We recorded optical signals
      from the left prefrontal cortex in 10 right-handed participants with a continuous
      wave instrument (DYNOT, NIRx, Brooklyn, NY). Visual stimuli were pictures of
      urban, landscape and seashore scenes with various vehicles as targets (target-to
      non-target ratio 1:6) presented at ISI=166 ms or 250 ms. Subjects mentally
      counted targets. Data were filtered at 2-30 Hz and artifactual components were
      identified visually (for heartbeat) and using the ICA weight matrix (for
      superficial layers). Optical signals were restored from the ICA components with
      artifactual components removed and then averaged over target and non-target
      epochs. After ICA processing, the event-related response was detected in 70%-100%
      of subjects. The refined signal showed a significant decrease from baseline
      within 200-300 ms after targets and a slight increase after non-targets. The
      temporal profile of the optical signal corresponded well to the profile of a
      "differential ERP response", the difference between targets and non-targets which
      peaks at 200 ms in similar object detection tasks. These results demonstrate that
      the detection of fast optical responses with continuous-wave instruments can be
      improved through the ICA method capable to remove noise, global interference and
      the activity of superficial layers. Fast optical signals may provide further
      information on brain processing during higher-order cognitive tasks such as rapid
      categorization of objects.

PMID- 18725215
TI  - The influence of gender and personality traits on individual difference in
      auditory mismatch: a magnetoencephalographic (MMNm) study.
AB  - The mismatch negativity (MMN; and its magnetic counterpart, MMNm) is widely used
      to assess early-stage auditory cortical function in humans and its impairment in
      various neuropsychiatric disorders. To establish MMN as a useful clinical tool
      for objective monitoring of auditory cortical function in an individual, we
      investigated the effect of gender and personality traits on individual difference
      in MMNm in healthy subjects. Participants were 88 healthy adults (31 women and 57
      men). The MMNm in response to the duration or frequency change of tones and those
      in response to across-phoneme change between vowels /a/ and /o/ were recorded
      using 204-channel whole-head magnetoencephalography. The temperament and
      character inventory (TCI) was used to assess individual personality traits. Women
      were associated with significantly delayed peak latency of phonetic MMNm for the
      right hemisphere compared with men. Men had greater strength of tonal duration
      MMNm for the left hemisphere than women. Additionally, the persistence score
      predicted the strength of phonetic MMNm for the left hemisphere in the combined
      sample and the tonal duration MMNm for the left hemisphere in men; reward
      dependence predicted the latency of the tonal duration MMNm for the left
      hemisphere in men; and cooperativeness predicted the strength of the tonal
      frequency MMNm for the right hemisphere in women. These results suggest that
      gender and personality traits have an effect on individual variability of the
      MMNm. Our observation may provide useful information to establish MMN/MMNm as a
      clinical tool for monitoring auditory cortical function on an individual basis.

PMID- 18725216
TI  - Fructose-1,6-bisphosphate does not preserve ATP in hypoxic-ischemic neonatal
      cerebrocortical slices.
AB  - Fructose-1,6-bisphosphate (FBP), an endogenous intracellular metabolite in
      glycolysis, was found in many preclinical studies to be neuroprotective during
      hypoxia-ischemia (HI) when administered exogenously. We looked for HI
      neuroprotection from FBP in a neonatal rat brain slice model, using 14.1 T
      (1)H/(31)P/(13)C NMR spectroscopy of perchloric acid slice extracts to ask: 1) if
      FBP preserves high energy phosphates during HI; and 2) if exogenous [1-(13)C]FBP
      enters cells and is glycolytically metabolized to [3-(13)C]lactate. We also
      asked: 3) if substantial superoxide production occurs during and after HI,
      thinking such might be treatable by exogenous FBP's antioxidant effects.
      Superfused P7 rat cerebrocortical slices (350 mum) were treated with 2 mM FBP
      before and during 30 min of HI, and then given 4 h of recovery with an FBP-free
      oxygenated superfusate. Slices were removed before HI, at the end of HI, and at 1
      and 4 h after HI. FBP did not improve high energy phosphate levels or change (1)H
      metabolite profiles. Large increases in [3-(13)C]lactate were seen with (13)C
      NMR, but the lactate fractional enrichment was always (1.1+/-0.5)%, implying that
      all of lactate's (13)C was natural abundance (13)C, that none was from metabolism
      of (13)C-FBP. FBP had no effect on the fluorescence of ethidium produced from
      superoxide oxidation of hydroethidine. Compared to control slices, ethidium
      fluorescence was 25% higher during HI and 50% higher at the end of recovery.
      Exogenous FBP did not provide protection or enter glycolysis. Its use as an
      antioxidant might be worth studying at higher FBP concentrations.

PMID- 18725217
TI  - Follicle survival and growth to antral stages in short-term murine ovarian
      cortical transplants after Cryologic solid surface vitrification or slow-rate
      freezing.
AB  - This study was designed to asses murine preantral follicle survival and growth,
      after cryopreservation of ovarian tissue by two different methodologies, solid
      surface vitrification by the Cryologic vitrification method (CVM) and slow-rate
      freezing (SRF). Cryotreated tissue was stored in liquid nitrogen for 24h, and
      upon warming follicle viability was assessed by live/dead fluorescent probes, and
      by 7-day autotransplantation of both cryotreated tissue types to the left and
      right kidney capsule of the donor animals (n=16). The live/dead assay immediately
      upon tissue warming did not allow a distinction to be made in terms of follicle
      viability between the CVM and SRF cryoprocedure. In grafted tissue, follicular
      survival and growth was assessed by conventional histological examination and
      proliferating cell nuclear antigen immunohistochemistry. In each experimental
      group (control, CVM and SRF), follicles were classified according to
      developmental stage, and a comparison of the proportions of follicle stages
      between the three groups was executed by statistical analysis of variance. The
      fraction of primordial follicles in CVM and SRF grafts significantly decreased as
      compared to control tissue, whereas intermediary and primary follicles
      significantly increased. The proportion of secondary and antral follicles after
      SRF was significantly larger than after CVM, but did not differ significantly
      between CVM and control tissue. The observed massive follicle activation is a
      typical transplantation effect, but testifies to the survival of cryopreserved
      follicles. In both types of cryotreated tissue, growing follicles, including
      antral stage, were present in grafts from all recipient animals. The
      significantly more abundant further developed stages in SRF treated tissue,
      however, suggest that CVM treated tissue may have suffered a growth disadvantage.
      To our knowledge, this is the first time that the CVM technique has been utilized
      to vitrify preantral follicles.

PMID- 18725218
TI  - Trypanosoma cruzi: an analysis of the minicircle hypervariable regions diversity
      and its influence on strain typing.
AB  - The current intraspecific nomenclature in Trypanosoma cruzi describes two major
      lineages, named T. cruzi I and T. cruzi II, and five sublineages within T. cruzi
      II, named IIa, IIb, IIc, IId and IIe. The polymorphism of minicircle
      hypervariable regions (mHVRs) of T. cruzi has been used in many studies for the
      molecular characterization of parasite populations directly from biological
      samples. However, the molecular bases that allow strain typing by these markers
      are still unclear. In this work we examined forty cloned mHVRs sequences of CL
      Brener reference strain (IIe sublineage), and we found a predominant group of
      sequences, with 40% of frequency in this strain, with a 97% of identity among
      them. Out of the forty clones analyzed, we identified other less representative
      types, and a few unique ones. This predominant sequence is also present in
      different reference strains belonging to the other main T. cruzi lineages and
      sublineages (TcI, IIa, IIb, IIc and IId) although in a many thousand times lower
      frequency than in the CL-Brener strain, as shown by semiquantitative PCR.
      Similarly, predominant mHVR sequences previously described for TcIId strains,
      were clearly more frequent (many thousand times higher) in the IId reference
      strain analyzed by us (Mncl2) than within the reference strains belonging to the
      other lineages and sublineages. The analysis of the cloned sequences shows that
      more sequences than just the major one contribute to define the global pattern of
      mHVRs RFLP in the CL-Brener strain. The possible usefulness of these predominant
      sequences for typing TcIId and TcIIe sublineages by semiquantitative PCR, as well
      as the possible role of these sequences in genotype identification by mHVR probes
      are discussed.

PMID- 18725219
TI  - Stabilization of beta-catenin induces pancreas tumor formation.
AB  - BACKGROUND & AIMS: beta-Catenin signaling within the canonical Wnt pathway is
      essential for pancreas development. However, the pathway is normally down
      regulated in the adult organ. Increased cytoplasmic and nuclear localization of
      beta-catenin can be detected in nearly all human solid pseudopapillary neoplasms
      (SPN), a rare tumor with low malignant potential. Conversely, pancreatic ductal
      adenocarcinoma (PDA) accounts for the majority of pancreatic tumors and is among
      the leading causes of cancer death. Whereas activating mutations within beta
      catenin and other members of the canonical Wnt pathway are rare, recent reports
      have implicated Wnt signaling in the development and progression of human PDA.
      Here, we sought to address the role of beta-catenin signaling in pancreas
      tumorigenesis. METHODS: Using Cre/lox technology, we conditionally activated beta
      catenin in a subset of murine pancreatic cells in vivo. RESULTS: Activation of
      beta-catenin results in the formation of large pancreatic tumors at a high
      frequency in adult mice. These tumors resemble human SPN based on morphologic and
      immunohistochemical comparisons. Interestingly, stabilization of beta-catenin
      blocks the formation of pancreatic intraepithelial neoplasia (PanIN) in the
      presence of an activating mutation in Kras that is known to predispose
      individuals to PDA. Instead, mice in which beta-catenin and Kras are concurrently
      activated develop distinct ductal neoplasms that do not resemble PanIN lesions.
      CONCLUSIONS: These results demonstrate that activation of beta-catenin is
      sufficient to induce pancreas tumorigenesis. Moreover, they indicate that the
      sequence in which oncogenic mutations are acquired has profound consequences on
      the phenotype of the resulting tumor.

PMID- 18725220
TI  - A controlled pharmacogenetic trial of sibutramine on weight loss and body
      composition in obese or overweight adults.
AB  - BACKGROUND & AIMS: Weight loss in response to sibutramine is highly variable. We
      assessed the association of specific markers of polymorphisms of candidate
      alpha2A adrenoreceptor, 5-HT transporter, and GNbeta3 genes and weight loss with
      sibutramine. METHODS: We conducted a randomized, double-blind, pharmacogenetic
      study of behavioral therapy and sibutramine (10 or 15 mg daily) or placebo for 12
      weeks in 181 overweight or obese participants. We measured body weight, body mass
      index, body composition, gastric emptying, and genetic variation (alpha2A C1291G,
      5-HTTLPR, and GNbeta3 C825T genotypes). Analysis of covariance was used to assess
      treatment effects on and associations of the specific markers of candidate genes
      with weight loss and body composition. RESULTS: Sibutramine, 10 and 15 mg, caused
      weight loss (P = .009); there was a statistically significant gene by dose
      interaction for GNbeta3 genotype. For each candidate gene, significant treatment
      effects at 12 weeks were observed (P < .017) for all specific genotype variants
      (Delta weight loss in the 2 sibutramine doses vs placebo): alpha2A CC (Delta,
      approximately 5 kg), GNbeta3 TC/TT (Delta, approximately 6 kg), and 5-HTTLPR
      LS/SS (Delta, approximately 4.5 kg). Gene pairs resulted in significantly greater
      sibutramine treatment effects on weight (both P < .002): in participants with 5
      HTTLPR LS/SS with GNbeta3 TC/TT; Delta, approximately 6 kg and those with alpha2A
      CC with GNbeta3 TC/TT; Delta, approximately 8 kg; however, effects were not
      synergistic. Treatment with sibutramine also resulted in significantly greater
      reduction of body fat for specific alpha2A CC and GNbeta3 TC/TT genotype variants
      individually (both P < .02). CONCLUSIONS: Patient selection based on candidate
      genes may enhance response to multidimensional sibutramine and behavioral therapy
      for obesity.

PMID- 18725221
TI  - Definition of phenotypic characteristics of childhood-onset inflammatory bowel
      disease.
AB  - BACKGROUND & AIMS: Childhood-onset inflammatory bowel disease (IBD) might be
      etiologically different from adult-onset IBD. We analyzed disease phenotypes and
      progression of childhood-onset disease and compared them with characteristics of
      adult-onset disease in patients in Scotland. METHODS: Anatomic locations and
      behaviors were assessed in 416 patients with childhood-onset (276 Crohn's disease
      [CD], 99 ulcerative colitis [UC], 41 IBD type unclassified [IBDU] diagnosed
      before seventeenth birthday) and 1297 patients with adult-onset (596 CD, 701 UC)
      IBD using the Montreal classification. RESULTS: At the time of diagnosis in
      children, CD involved small bowel and colon (L3) in 51% (138/273), colon (L2) in
      36%, and ileum (L1) in 6%; the upper gastrointestinal (GI) tract (L4) was also
      affected in 51%. In 39%, the anatomic extent increased within 2 years. Behavioral
      characteristics progressed; 24% of children developed stricturing or penetrating
      complications within 4 years (vs 9% at diagnosis; P < .0001; odds ratio [OR],
      3.32; 95% confidence interval [CI], 1.86-5.92). Compared with adults, childhood
      onset disease was characterized by a "panenteric" phenotype (ileocolonic plus
      upper GI [L3+L4]; 43% vs 3%; P < .0001; OR, 23.36; 95% CI, 13.45-40.59) with less
      isolated ileal (L1; 2% vs 31%; P < .0001; OR, 0.06; 95% CI, 0.03-0.12) or colonic
      disease (L2; 15% vs 36%; P < .0001; OR, 0.31; 95% CI, 0.21-0.46). UC was
      extensive in 82% of the children at diagnosis, versus 48% of adults (P < .0001;
      OR, 5.08; 95% CI, 2.73-9.45); 46% of the children progressed to develop extensive
      colitis during follow-up. Forty-six percent of children with CD and 35% with UC
      required immunomodulatory therapy within 12 months of diagnosis. The median time
      to first surgery was longer in childhood-onset than adult-onset patients with CD
      (13.7 vs 7.8 years; P < .001); the reverse was true for UC. CONCLUSIONS:
      Childhood-onset IBD is characterized by extensive intestinal involvement and
      rapid early progression.

PMID- 18725222
TI  - Murine embryonic stem cell-derived pancreatic acinar cells recapitulate features
      of early pancreatic differentiation.
AB  - BACKGROUND & AIMS: Acinar cells constitute 90% of the pancreas epithelium, are
      polarized, and secrete digestive enzymes. These cells play a crucial role in
      pancreatitis and pancreatic cancer. However, there are limited models to study
      normal acinar cell differentiation in vitro. The aim of this work was to generate
      and characterize purified populations of pancreatic acinar cells from embryonic
      stem (ES) cells. METHODS: Reporter ES cells (Ela-pur) were generated that stably
      expressed both beta-galactosidase and puromycin resistance genes under the
      control of the elastase I promoter. Directed differentiation was achieved by
      incubation with conditioned media of cultured fetal pancreatic rudiments and
      adenoviral-mediated co-expression of p48/Ptf1a and Mist1, 2 basic helix-loop
      helix transcription factors crucial for normal pancreatic acinar development and
      differentiation. RESULTS: Selected cells expressed multiple markers of acinar
      cells, including digestive enzymes and proteins of the secretory pathway,
      indicating activation of a coordinated differentiation program. The genes coding
      for digestive enzymes were not regulated as a single module, thus recapitulating
      what occurs during in vivo pancreatic development. The generated cells displayed
      transient agonist-induced Ca(2+) mobilization and showed a typical response to
      physiologic concentrations of secretagogues, including enzyme synthesis and
      secretion. Importantly, these effects did not imply the acquisition of a mixed
      acinar-ductal phenotype. CONCLUSIONS: These studies allow the generation of
      almost pure acinar-like cells from ES cells, providing a normal cell-based model
      for the study of the acinar differentiation program in vitro.

PMID- 18725223
TI  - Impact of wide-angle, high-definition endoscopy in the diagnosis of colorectal
      neoplasia: a randomized controlled trial.
AB  - BACKGROUND & AIMS: It is essential to optimize standard colonoscopy technique to
      be able to increase polyp detection. We sought to compare the performance of
      colonoscopy using a high-definition, wide-angle endoscope (HDE) versus a standard
      colonoscope (SC) for the detection of colorectal neoplasia. PATIENTS AND METHODS:
      All consecutive consenting adult patients referred from primary care centers were
      included and randomly assigned at a 1:1 ratio to undergo HDE or SC. Times to
      reach and withdraw from the cecum were measured. Morphology, size, location, and
      pathologic diagnosis of each polyp were recorded. Sample size calculation
      resulted in a total of 682 patients needed. RESULTS: A total of 693 consecutive
      patients fulfilled all inclusion criteria (73 excluded owing to insufficient
      bowel preparation). Each arm included 310 patients with no baseline
      characteristic differences. Time to reach the cecum was slightly superior for SC
      (8.9 +/- 4.8 minutes vs 8.2 +/- 4.5 minutes; P = .055). Pathology examination was
      feasible in 418 lesions (272 adenomas, 109 hyperplastic polyps, and 37
      inflammatory lesions). Both techniques detected a similar number and type of
      lesions, and there were no differences in the distribution along the colon, in
      the degree of dysplasia, or morphology of adenomas. The per-patient basis
      analyses demonstrated that there were no differences between the 2 arms of the
      study in the detection rates of polyps (SC, 0.84 +/- 1.59; HDE, 0.83 +/- 1.30),
      adenomas (0.45 +/- 1.07 vs 0.43 +/- 0.87), small adenomas (0.22 +/- 0.71 vs 0.28
      +/- 0.78), flat adenomas (0.30 +/- 0.91 vs 0.21 +/- 0.63), or hyperplastic polyps
      (0.16 +/- 0.50 vs 0.18 +/- 0.54). CONCLUSION: HDE did not detect significantly
      more colorectal neoplasia than SC.

PMID- 18725224
TI  - Antiviral suppression vs restoration of RIG-I signaling by hepatitis C protease
      and polymerase inhibitors.
AB  - BACKGROUND & AIMS: Expression of the nonstructural protein (NS)3/4A protease in
      cells infected with hepatitis C virus (HCV) results in cleavage of the
      mitochondrial antiviral-signaling protein (MAVS) and disruption of signaling
      pathways that lead to viral activation of interferon regulatory factor 3 (IRF-3)
      and synthesis of type 1 interferons (IFN-alpha/beta). High concentrations of
      inhibitors of NS3/4A reverse this signaling defect, but quantitative analyses of
      this potential therapeutic effect are lacking. This study quantitatively assessed
      the rescue of IRF-3 signaling by NS3/4A inhibitors, compared with in vitro
      antiviral activity. METHODS: Antiviral activities of 2 NS3/4A protease inhibitors
      (TMC435350 and an analog, TMC380765) and a nonnucleoside polymerase inhibitor
      (Tib-3) were determined in HCV replicon cells and in cells infected with genotype
      1a and 2a viruses. The capacity to rescue IRF-3 activation in these cells was
      assessed by monitoring IFN-beta promoter activity following challenge with Sendai
      virus. Inhibitor-induced changes in NS3 and MAVS expression were assessed in
      immunoblots. RESULTS: Both protease inhibitors were capable of rescuing IFN-beta
      promoter activation but only at concentrations approximately 100-fold the
      antiviral 50% effective concentration (EC(50)) for genotype 1 virus. No rescue
      was observed with the polymerase inhibitor, even at a concentration 600-fold
      greater than the EC(50). IRF-3 activation did not correlate with reductions in
      NS3/4A levels or detection of full-length MAVS. Overexpression of the product of
      NS3/4A cleavage of MAVS did not result in a dominant-negative effect on
      signaling. CONCLUSIONS: NS3/4A protease inhibitors can restore IRF-3 signaling in
      HCV-infected cells but only at concentrations far in excess of the antiviral
      EC(50).

PMID- 18725225
TI  - In silico analyses of peptide paracrines/hormones in Aphidoidea.
AB  - The Aphidoidea is an insect superfamily comprising most of the known aphid
      species. While small in size, these animals are of considerable economic
      importance as many members of this taxon are serious agricultural pests,
      inflicting physical damage upon crop plants and serving as vectors in the
      transmission of viral plant diseases. In terms of identifying the
      paracrines/hormones used to modulate behavior, particularly peptides, members of
      the Aphidoidea have largely been ignored, as it is not tractable to isolate the
      large pools of tissue needed for standard biochemical investigations. Here, a
      bioinformatics approach to peptide discovery has been used to overcome this
      limitation of scale. Specifically, in silico searches of publicly accessible
      aphidoidean ESTs were conducted to identify transcripts encoding putative
      peptides precursors, with the mature peptides contained within them deduced using
      peptide processing software and homology to known arthropod sequences. In total,
      39 ESTs encoding putative peptides precursors were identified from four aphid
      species: Acyrthosiphon pisum (14 ESTs), Aphis gossypii (four ESTs), Myzus
      persicae (20 ESTs) and Toxoptera citricida (one EST). These precursors included
      ones predicted to encode isoforms of B-type allatostatin, crustacean cardioactive
      peptide, FMRFamide-related peptide (both myosuppressin and short neuropeptide F
      subfamilies), insect kinin, orcokinin, proctolin,
      pyrokinin/periviscerokinin/pheromone biosynthesis activating neuropeptide,
      SIFamide and tachykinin-related peptide. In total, 83 peptides were characterized
      from the identified precursors, most novel, including two B-type allatostatins
      possessing the variant -WX(7)Wamide motif, two N-terminally extended proctolin
      isoforms and an N-terminally truncated and substituted SIFamide. Collectively,
      these results expand greatly the number of known/predicted aphid peptide
      paracrines/hormones, and provide a strong foundation for future molecular and
      physiological investigations of peptidergic control in this insect group.

PMID- 18725226
TI  - Accumulation of diverse parasite genotypes within the bivalve second intermediate
      host of the digenean Gymnophallus sp.
AB  - The complex life cycle of digenean trematodes with alternating stages of asexual
      multiplication and sexual reproduction can generate interesting within-host
      population genetic patterns. Metacercarial stages found in the second
      intermediate host are generally accumulated from the environment. Highly mobile
      second intermediate hosts can sample a broad range of cercarial genotypes and
      accumulate genetically diverse packets of metacercariae, but it is unclear
      whether the same would occur in systems where the second intermediate host is
      relatively immobile and cercarial dispersal is the sole mechanism that can
      maintain genetic homogeneity at the population level. Here, using polymorphic
      microsatellite markers, we addressed this issue by genotyping metacercariae of
      the trematode Gymnophallus sp. from the New Zealand cockle Austrovenus
      stutchburyi. Despite the relatively sessile nature of the second intermediate
      host of Gymnophallus, very high genotypic diversity of metacercariae was found
      within cockles, with only two cockles harbouring multiple copies of a single
      clonal lineage. There was no evidence of population structuring at the scale of
      our study, suggesting the existence of a well-mixed population. Our results
      indicate that (i) even relatively sessile second intermediate hosts can
      accumulate a high diversity of genotypes and (ii) the dispersal ability of
      cercariae, whether passive or not, is much greater than expected for such small
      and short-lived organisms. The results also support the role of the second
      intermediate host as an accumulator of genetic diversity in the trematode life
      cycle.

PMID- 18725227
TI  - Amfor expression in the honeybee brain: a trigger mechanism for nurse-forager
      transition.
AB  - The honeybee's colony fitness relies on an optimized age-dependent division of
      labor. Transition from nursing activities to foraging activities is associated
      with an increase in the expression of the Amfor gene. Ben-Shahar et al. [Ben
      Shahar, Y., Robichon, A., Sokolowski, M.B., Robinson, G.E., 2002. Influence of
      gene action across different time scales on behavior. Science 296, 741-744]
      showed that the Amfor transcripts and their gene products are involved in
      regulating the transition from one task to the next. In this study, we
      investigated the trajectory of the expression of this gene in the brain over
      time. The expression pattern could contribute to our understanding of the
      involvement of Amfor in the transition process. Is there a gradual increase in
      transcript or a peak in expression triggering a downstream path of multiple
      differential gene expression? Hereto, bees were sampled from colonies containing
      marked 1-day-old bees every 2 or 3 days around the expected time of transition
      from nurse to forager, from day 13 to 25. To quantify Amfor transcript in the
      brain, we developed a real-time RT-PCR assay, based on Taqman technology, using
      fluorescent probes. Results revealed a trigger mechanism rather than a continued
      elevation of Amfor expression. The appearance of an Amfor expression peak
      suggests that under normal physiological conditions foraging behavior is, at
      least in part, due to a trigger-effect of Amfor.

PMID- 18725228
TI  - Effects of Heliothis virescens ascovirus (HvAV-3e) on a novel host, Crocidolomia
      pavonana (Lepidoptera: Crambidae).
AB  - Ascoviruses are double-stranded DNA viruses which cause fatal disease in
      lepidopteran host larvae. They induce a unique pathology, causing cleavage of
      host cells into virion-containing vesicles. With the single exception of
      Diadromus pulchellus ascovirus, all ascoviruses have been exclusively reported
      from the Noctuidae. To investigate whether Heliothis virescens AV (HvAV-3e) has a
      broader host range at the family level, larvae of Crocidolomia pavonana F.
      (Lepidoptera: Crambidae), a major pest of brassica crops in tropical and sub
      tropical regions of the Old World and Australasia, were inoculated with HvAV-3e.
      Larvae were readily infected by the ascovirus and feeding, growth and survival
      were significantly affected. However, the milky white discolouration of the
      haemolymph which is characteristic of ascovirus infection in noctuid hosts was
      not apparent. In further contrast to infected noctuid host larvae that do not
      develop to the pupal stage, a significant proportion of infected C. pavonana
      larvae pupated but all were killed at this stage. Thus, C. pavonana appears to be
      a semi-permissive host of the ascovirus, the presence of such hosts in the field
      might be an explanation for the conundrum for the ascovirus-noctuid-wasp
      relationship, helping explain the persistence of the ascovirus.

PMID- 18725229
TI  - C4-dicarboxylates sensing mechanism revealed by the crystal structures of DctB
      sensor domain.
AB  - C(4)-dicarboxylates are the major carbon and energy sources during the symbiotic
      growth of rhizobia. Responses to C(4)-dicarboxylates depend on typical two
      component systems (TCS) consisting of a transmembrane sensor histidine kinase and
      a cytoplasmic response regulator. The DctB-DctD system is the first identified
      TCS for C(4)-dicarboxylates sensing. Direct ligand binding to the sensor domain
      of DctB is believed to be the first step of the sensing events. In this report,
      the water-soluble periplasmic sensor domain of Sinorhizobium meliloti DctB
      (DctBp) was studied, and three crystal structures were solved: the apo protein, a
      complex with C(4) succinate, and a complex with C(3) malonate. Different from the
      two structurally known CitA family of carboxylate sensor proteins CitA and DcuS,
      the structure of DctBp consists of two tandem Per-Arnt-Sim (PAS) domains and one
      N-terminal helical region. Only the membrane-distal PAS domain was found to bind
      the ligands, whereas the proximal PAS domain was empty. Comparison of DctB, CitA,
      and DcuS suggests a detailed stereochemistry of C(4)-dicarboxylates ligand
      perception. The structures of the different ligand binding states of DctBp also
      revealed a series of conformational changes initiated upon ligand binding and
      propagated to the N-terminal domain responsible for dimerization, providing
      insights into understanding the detailed mechanism of the signal transduction of
      TCS histidine kinases.

PMID- 18725230
TI  - A game-theoretic model of kleptoparasitic behavior in polymorphic populations.
AB  - Kleptoparasitism, the stealing of food by one animal from another, is a
      widespread biological phenomenon. In this paper we build upon earlier models to
      investigate a population of conspecifics involved in foraging and, potentially,
      kleptoparasitism. We assume that the population is composed of four types of
      individuals, according to their strategic choices when faced with an opportunity
      to steal and to resist an attack. The fitness of each type of individual depends
      upon various natural parameters, for example food density, the handling time of a
      food item and the probability of mounting a successful attack against resistance,
      as well as the choices that they make. We find the evolutionarily stable
      strategies (ESSs) for all parameter combinations and show that there are six
      possible ESSs, four pure and two mixtures of two strategies, that can occur. We
      show that there is always at least one ESS, and sometimes two or three. We
      further investigate the influence of the different parameters on when each type
      of solution occurs.

PMID- 18725231
TI  - Mathematical modelling of tumour acidity.
AB  - Acid-mediated tumour invasion is receiving increasing experimental and clinical
      attention. Previous models proposed to describe this phenomenon failed to capture
      key properties of the system, such as the existence of the benign steady state,
      or predicted incorrectly the size of the inter-tissue gap. Here we show that
      taking proper account of quiescence ameliorates these drawbacks as well as
      revealing novel behaviour. The simplicity of the model allows us to fully
      identify the key parameters controlling different aspects of behaviour.

PMID- 18725232
TI  - Co-expression of cytokeratin 8 and breast cancer resistant protein indicates a
      multifactorial drug-resistant phenotype in human breast cancer cell line.
AB  - AIMS: The aim was to determine whether increased CK8 and BCRP expression
      cooperatively contribute to multidrug resistance (MDR) in MCF-7/MX cells.
      Accumulating evidence suggests that the development and maintenance of cancer MDR
      involves complex multimodal mechanisms that interact concomitantly and
      complementarily. In this report, we observed elevated expression of cytokeratin 8
      (CK8) in MCF-7/MX, a mitoxantrone (MX)-selected human breast tumor cell line with
      the MDR phenotype known as overexpression of breast cancer resistant protein
      (BCRP). MAIN METHODS: Gene transfection methods were used to express CK8 and BCRP
      in NIH3T3 fibroblasts, individually or in combination. KEY FINDINGS: Taken
      together, our present study suggests that CK8 together with BCRP may play
      significant roles in conferring the multifactorial MDR phenotype of MCF-7/MX
      cells, but may act independently via potentially different mechanisms. Although
      expressing either CK8 or BCRP alone was able to confer resistance to
      mitoxantrone, cells co-expressing both proteins demonstrated significantly
      increased drug resistance. Furthermore, RNAi knockdown of CK8 and BCRP, alone and
      in combination, in MCF-7/MX cells significantly attenuated their resistance to
      chemotherapeutic agents. Interestingly, in contrast to inhibition of BCRP
      expression via anti-BCRP shRNA vector transfection, reversal of mitoxantrone
      resistance by transfection with anti-CK8 shRNA was not accompanied by an increase
      in intracellular drug accumulation. SIGNIFICANCE: Combinational approaches that
      target multiple drug-resistance-related molecules/pathways in cancer cells may
      represent more efficacious strategies to overcome MDR.

PMID- 18725233
TI  - Global stability of an SIR epidemic model with information dependent vaccination.
AB  - We study the global behavior of a non-linear susceptible-infectious-removed (SIR)
      like epidemic model with a non-bilinear feedback mechanism, which describes the
      influence of information, and of information-related delays, on a vaccination
      campaign. We upgrade the stability analysis performed in d'Onofrio et al. [A.
      d'Onofrio, P. Manfredi, E. Salinelli, Vaccinating behavior, information, and the
      dynamics of SIR vaccine preventable diseases, Theor. Popul. Biol. 71 (2007) 301)
      and, at same time, give a special example of application of the geometric method
      for global stability, due to Li and Muldowney. Numerical investigations are
      provided to show how the stability properties depend on the interplay between
      some relevant parameters of the model.

PMID- 18725234
TI  - Tissue factor-containing microparticles released from mesangial cells in response
      to high glucose and AGE induce tube formation in microvascular cells.
AB  - Hyperglycaemia and the associated formation of advanced glycation end-products
      (AGE) have been implicated in the pathogenesis of diabetic vasculopathy. In
      addition to its role in coagulation, tissue factor (TF) is known to regulate
      vascular proliferation and angiogenesis. In this study, the influence of AGE and
      glucose on the expression of TF in human renal mesangial cells (HRMC) and the
      subsequent induction of capillary formation by human dermal microvascular
      endothelial cells (HDMEC) were measured. Furthermore, the activity of TF,
      incorporated into microparticles was investigated. Both AGE and elevated glucose
      were capable of upregulating the expression of TF expression in a concentration
      dependent manner in HRMC but not in HDMEC. This TF antigen and activity in the
      conditioned media from HRMC was associated with microparticles. Moreover, the
      formation of capillaries was readily induced on supplementation of HDMEC with
      conditioned media, from AGE-treated or high glucose-treated HRMC but not on
      incubation of HDMEC with either AGE or hyperphysiological concentrations of
      glucose. Furthermore, the rate of capillary formation was suppressed on
      incubation of the conditioned media with a polyclonal antibody against TF but not
      against VEGF. This study indicates that TF-containing microparticles are an
      important pro-inflammatory mediator acting as a mediator between elevated glucose
      and the development of diabetic vasculopathy by altering the angiogenic
      properties of endothelial cells and offers one explanation for the correlation
      between diabetes and microvascular disease.

PMID- 18725235
TI  - Bidirectional translational research: Progress in understanding addictive
      diseases.
AB  - The focus of this review is primarily on recent developments in bidirectional
      translational research on the addictions, within the Laboratory of the Biology of
      Addictive Diseases at The Rockefeller University. This review is subdivided into
      major interacting aspects, including (a) Investigation of neurobiological and
      molecular adaptations (e.g., in genes for the opioid receptors or endogenous
      neuropeptides) in response to cocaine or opiates, administered under laboratory
      conditions modeling chronic patterns of human self-exposure (e.g., chronic
      escalating "binge"). (b) The impact of such drug exposure on the hypothalamic
      pituitary-adrenal (HPA) axis and interacting neuropeptidergic systems (e.g.,
      opioid, orexin and vasopressin). (c) Molecular genetic association studies using
      candidate gene and whole genome approaches, to define particular systems involved
      in vulnerability to develop specific addictions, and response to pharmacotherapy.
      (d) Neuroendocrine challenge studies in normal volunteers and current addictive
      disease patients along with former addicts in treatment, to investigate
      differential pharmacodynamics and responsiveness of molecular targets, in
      particular those also investigated in the experimental and molecular genetic
      approaches as described above.

PMID- 18725237
TI  - Modulation of emotions associated with images of human pain using anodal
      transcranial direct current stimulation (tDCS).
AB  - Viewing images of other humans in pain elicits a variety of responses including
      distress, anxiety, and a sensation that is similar to pain. We aimed to evaluate
      whether transcranial direct current stimulation (tDCS) could be effective in
      modulating the emotional aspects of pain as to further explore mechanisms of tDCS
      in pain relief. Twenty-three healthy subjects rated images with respect to
      unpleasantness and discomfort/pain (baseline), and then received stimulation with
      tDCS under four different conditions of stimulation: anodal tDCS of the left
      primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), occipital
      cortex (V1); and sham tDCS. The order of conditions was randomized and
      counterbalanced across subjects. During each stimulation session (after 3 min of
      stimulation), subjects were shown a new set of aversive images and were again
      asked to rate the images with respect to unpleasantness and discomfort/pain. The
      results showed that ratings of unpleasantness and discomfort/pain were
      significantly decreased during DLPFC tDCS only, as compared to baseline and sham
      tDCS. The other conditions of stimulation (M1 and V1 tDCS) did not result in any
      significant changes. These results support the notion that DLPFC is a critical
      area for the emotional processing of pain and also suggests that DLPFC may be a
      potential target of stimulation for alleviation of pain with a significant
      emotional-affective component. Our results also suggest that the mechanism of
      tDCS in modulating emotional pain involve pathways that are independent of those
      modulating the somatosensory perception of pain.

PMID- 18725236
TI  - Neurobiological substrates for the dark side of compulsivity in addiction.
AB  - Drug addiction can be defined by a compulsion to seek and take drug, loss of
      control in limiting intake, and the emergence of a negative emotional state when
      access to the drug is prevented. Drug addiction impacts multiple motivational
      mechanisms and can be conceptualized as a disorder that progresses from
      impulsivity (positive reinforcement) to compulsivity (negative reinforcement).
      The construct of negative reinforcement is defined as drug taking that alleviates
      a negative emotional state. The negative emotional state that drives such
      negative reinforcement is hypothesized to derive from dysregulation of key
      neurochemical elements involved in reward and stress within the basal forebrain
      structures involving the ventral striatum and extended amygdala. Specific
      neurochemical elements in these structures include not only decreases in reward
      neurotransmission, such as decreases in dopamine and opioid peptide function in
      the ventral striatum, but also recruitment of brain stress systems, such as
      corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal
      from all major drugs of abuse produces increases in reward thresholds, increases
      in anxiety-like responses, and increases in extracellular levels of CRF in the
      central nucleus of the amygdala. CRF receptor antagonists also block excessive
      drug intake produced by dependence. A brain stress response system is
      hypothesized to be activated by acute excessive drug intake, to be sensitized
      during repeated withdrawal, to persist into protracted abstinence, and to
      contribute to the compulsivity of addiction. Other components of brain stress
      systems in the extended amygdala that interact with CRF and may contribute to the
      negative motivational state of withdrawal include norepinephrine, dynorphin, and
      neuropeptide Y. The combination of loss of reward function and recruitment of
      brain stress systems provides a powerful neurochemical basis for a negative
      emotional state that is responsible for the negative reinforcement driving, at
      least in part, the compulsivity of addiction.

PMID- 18725238
TI  - More than (where the target) meets the eyes: disrupted visuomotor transformations
      in optic ataxia.
AB  - Visually guided reaching entails multiple coordinate frame transformations
      between retina-centered target location and body-centered limb location. Reaching
      errors in optic ataxia (OA) may be caused by disruptions to these
      transformations. Consistent with this proposal, previous studies report that
      reaching errors in OA depend primarily on the location of a target relative to
      the patient's gaze regardless of its location relative to the head or body
      midline. We attempted to replicate this finding by testing KE, a patient with OA
      following bilateral parietal and left premotor lesions (as well as significant
      non-specific white matter disease) on a reaching task that varied the orientation
      of his head and torso while holding the gaze-relative position of the target
      constant (always foveated). In contrast to previous reports, we observed that
      rotating the head or body away from the midline led to decreased reaching
      accuracy. Further analyses showed that multiple visuomotor transformation steps
      might have been disrupted in KE. These results suggest that gaze-relative target
      position is not the sole determinant of reaching errors in all OA patients.

PMID- 18725240
TI  - Experimentally manipulating perceptions regarding acupuncture elicits different
      responses to the identical acupuncture stimulation.
AB  - Excessive expectancy or an aversion to acupuncture makes it difficult to evaluate
      the efficacy of acupuncture during clinical trials. We investigated whether
      experimental manipulations of the perception of acupuncture could elicit
      different responses to identical acupuncture stimulation. Seventeen participants
      were assessed with the acupuncture belief scale (ABS) and by measuring tactile
      and pain sensitivity. Identical acupuncture-related pictures and either positive
      (positive group; n=9) or negative (negative group, n=8) statements related to
      treatment were presented, and participants used the self-assessment manikin (SAM)
      to rate each acupuncture-related image. Participants were stimulated with the
      same intensity for 5 min and then evaluated for acupuncture-induced, self
      reported pain. Heart rate variability (HRV) was measured before and after the
      acupuncture stimulation. Participants in the negative group were less valenced
      and more aroused in response to the same acupuncture picture compared to those in
      the positive group. Negative cognition regarding acupuncture modality resulted in
      a change of the relationship between the pre-experimental expectancy of
      acupuncture and self-reported pain. The negative group produced an increased low
      frequency component of HRV after acupuncture, whereas the positive group did not.
      Subjective and sympathetic responses to acupuncture can be modified by
      perception. Our findings may help to understand the psychological factors related
      to acupuncture modality.

PMID- 18725239
TI  - Differential effects of orthographic and phonological consistency in cortex for
      children with and without reading impairment.
AB  - One of the central challenges in mastering English is becoming sensitive to
      consistency from spelling to sound (i.e. phonological consistency) and from sound
      to spelling (i.e. orthographic consistency). Using functional magnetic resonance
      imaging (fMRI), we examined the neural correlates of consistency in 9-15-year-old
      Normal and Impaired Readers during a rhyming task in the visual modality. In line
      with our previous study [Bolger, D.J., Hornickel, J., Cone, N. E., Burman, D. D.,
      & Booth,J. R. (in press). Neural correlates of orthographic and phonological
      consistency effects in children. Human Brain Mapping], for Normal Readers, lower
      phonological and orthographic consistency were associated with greater activation
      in several regions including bilateral inferior/middle frontal gyri, bilateral
      anterior cingulate cortex as well as left fusiform gyrus. Impaired Readers
      activated only bilateral anterior cingulate cortex in response to decreasing
      consistency. Group comparisons revealed that, relative to Impaired Readers,
      Normal Readers exhibited a larger response in this network for lower phonological
      consistency whereas orthographic consistency differences were limited. Lastly,
      brain-behavior correlations revealed a significant relationship between skill
      (i.e. Phonological Awareness and non-word decoding) and cortical consistency
      effects for Impaired Readers in left inferior/middle frontal gyri and left
      fusiform gyrus. Impaired Readers with higher skill showed greater activation for
      higher consistency. This relationship was reliably different from that of Normal
      Readers in which higher skill was associated with greater activation for lower
      consistency. According to single-route or connectionist models, these results
      suggest that Impaired Readers with higher skill devote neural resources to
      representing the mapping between orthography and phonology for higher consistency
      words, and therefore do not robustly activate this network for lower consistency
      words.

PMID- 18725241
TI  - Applications of estradiol and testosterone assays in the management of the
      infertile female patient.
AB  - A collaborative effort to improve steroid hormone measurements in patient care
      was convened by the Centers for Disease Control in March 2008 to discuss the need
      for enhanced performance and standardization of clinical estradiol and
      testosterone assays. This article discusses the current status of estradiol and
      testosterone assays in the treatment of infertile women to include the assessment
      of ovarian reserve, ovulation induction and follicle tracking, ovarian
      hyperstimulation syndrome, and the role of testosterone in fertility management.

PMID- 18725242
TI  - In silico identification of anthropogenic chemicals as ligands of zebrafish sex
      hormone binding globulin.
AB  - Anthropogenic compounds with the capacity to interact with the steroid-binding
      site of sex hormone binding globulin (SHBG) pose health risks to humans and other
      vertebrates including fish. Building on studies of human SHBG, we have applied in
      silico drug discovery methods to identify potential binders for SHBG in zebrafish
      (Danio rerio) as a model aquatic organism. Computational methods, including;
      homology modeling, molecular dynamics simulations, virtual screening, and 3D QSAR
      analysis, successfully identified 6 non-steroidal substances from the ZINC
      chemical database that bind to zebrafish SHBG (zfSHBG) with low-micromolar to
      nanomolar affinities, as determined by a competitive ligand-binding assay. We
      also screened 80,000 commercial substances listed by the European Chemicals
      Bureau and Environment Canada, and 6 non-steroidal hits from this in silico
      screen were tested experimentally for zfSHBG binding. All 6 of these compounds
      displaced the [(3)H]5alpha-dihydrotestosterone used as labeled ligand in the
      zfSHBG screening assay when tested at a 33 microM concentration, and 3 of them
      (hexestrol, 4-tert-octylcatechol, and dihydrobenzo(a)pyren-7(8H)-one) bind to
      zfSHBG in the micromolar range. The study demonstrates the feasibility of large
      scale in silico screening of anthropogenic compounds that may disrupt or highjack
      functionally important protein:ligand interactions. Such studies could increase
      the awareness of hazards posed by existing commercial chemicals at relatively low
      cost.

PMID- 18725243
TI  - Seasonal dynamics of cylindrospermopsin and cyanobacteria in two German lakes.
AB  - Cylindrospermopsin (CYN) is a potent hepatotoxin produced by different
      cyanobacteria of the order Nostocales. Questions of major concern are: which
      species produce CYN, which are the seasonal patterns of CYN dynamics and how are
      they regulated? Therefore, we studied for the first time the seasonal dynamics of
      particulate and dissolved CYN concentrations, cyanobacterial abundance and
      environmental factors in two German lakes over 2 years. Total CYN reached maximum
      concentrations of 0.34 and 1.80 microg L(-1) in Melangsee and Langer See,
      respectively. In both lakes, maxima of the dissolved CYN fraction occurred later
      in the season than those of the particulate fraction, and it reached higher
      concentrations. This indicates that CYN is poorly decomposed and accumulates in
      the water. The cyanobacterial community in both lakes included several
      potentially CYN-producing species that did not correlate with CYN concentrations.
      Significant correlations between the particulate CYN concentrations and species
      biovolume were only found for Aphanizomenon gracile (r(s)=0.803) in Langer See
      indicating that this species is a CYN producer. Different correlations of CYN
      with abiotic factors in the two lakes indicate the presence of further undetected
      CYN producers as well as different regulation mechanisms of their dynamics and
      the variability of CYN.

PMID- 18725244
TI  - Solanaceous steroidal glycoalkaloids and poisoning by Solanum torvum, the
      normally edible susumber berry.
AB  - Ingestion of immature, environmentally stressed, or cultivar-specific Solanum
      species (particularly the potato) has been previously associated with
      gastrointestinal and neurological symptoms caused by solanaceous steroidal
      glycoalkaloids (SGAs). We report on two geographically, temporally disparate
      outbreaks of poisoning by susumber berries (Solanum torvum- Solanaceae) and on
      detection of alkaloids not present in non-toxic berries. Five family members in
      New York City participated in a traditional evening meal containing Jamaican
      susumber berries. All those consuming berries were symptomatic the following
      morning with varying degrees of gastrointestinal distress, dizziness, slurred
      speech, cranial nerve deficits, and ataxia. The most seriously afflicted patient
      developed hypertension, confusion, proximal upper extremity weakness, and
      hypercapnic respiratory failure requiring prolonged mechanical ventilation. A
      separate cohort of six patients in Toronto ate unripe Jamaican susumber berries.
      They presented 14h post-ingestion with varying degrees of diarrhea, weakness,
      facial paralysis, slurred speech, ataxia, early hypertension, and proximal
      weakness. Two patients had ventilatory decompensation; one required intubation.
      Poisonous berries appeared indistinguishable from non-toxic varieties. We
      isolated solasonine, larger amounts of solamargine, and other steroidal
      glycoalkaloids in the toxic berry strains. S. torvum poisoning can produce
      significant neurological and gastrointestinal effects which appear to be mediated
      by SGAs present in the berries.

PMID- 18725245
TI  - Dual-probe real-time PCR assay for detection of variola or other orthopoxviruses
      with dried reagents.
AB  - A real-time, multiplexed polymerase chain reaction (PCR) assay based on dried PCR
      reagents was developed. Only variola virus could be specifically detected by a
      FAM (6-carboxyfluorescein)-labeled probe while camelpox, cowpox, monkeypox and
      vaccinia viruses could be detected by a TET (6-carboxytetramethylrhodamine)
      labeled probe in a single PCR reaction. Approximately 25 copies of cloned variola
      virus DNA and 50 copies of genomic orthopoxviruses DNA could be detected with
      high reproducibility. The assay exhibited a dynamic range of seven orders of
      magnitude with a correlation coefficient value greater than 0.97. The sensitivity
      and specificity of the assay, as determined from 100 samples that contained
      nucleic acids from a multitude of bacterial and viral species were 96% and 98%,
      respectively. The limit of detection, sensitivity and specificity of the assay
      were comparable to standard real-time PCR assays with wet reagents. Employing a
      multiplexed format in this assay allows simultaneous discrimination of the
      variola virus from other closely related orthopoxviruses. Furthermore, the
      implementation of dried reagents in real-time PCR assays is an important step
      towards simplifying such assays and allowing their use in areas where cold
      storage is not easily accessible.

PMID- 18725246
TI  - A new and rapid genotypic assay for the detection of neuraminidase inhibitor
      resistant influenza A viruses of subtype H1N1, H3N2, and H5N1.
AB  - The neuraminidase of influenza viruses is the target of the inhibitors
      oseltamivir and zanamivir. Recent reports on influenza viruses with reduced
      susceptibility to neuraminidase inhibitors (NAI) are a cause for concern. Several
      amino acid substitutions, each as a consequence of one single nucleotide
      mutation, are known to confer resistance to NAI. An increase of NAI-resistant
      viruses appears to be likely as a result of a wider application of NAI for
      treatment and prophylaxis of seasonal influenza infections. Monitoring the
      occurrence and spread of resistant viruses is an important task. Therefore, RT
      PCR assays were developed with subsequent pyrosequencing analysis (PSQ-PCR).
      These assays allow a rapid, high-throughput and cost-effective screening of
      subtype A/H1N1, A/H3N2, and A/H5N1 viruses. Various specimens such as respiratory
      swabs, allantoic fluid, or cell-propagated viruses can be used and results are
      available within hours. Several A/H1N1, A/H3N2, and A/H5N1 viruses isolated from
      human and avian specimens were tested to evaluate the method. Positive controls
      encoding resistance-associated mutations were created using site-directed
      mutagenesis. The results obtained with these controls showed that the assay can
      discriminate clearly the wild-type virus from a mutant virus. The detection limit
      of minor virus variants within the viral quasispecies amounts to 10%.

PMID- 18725247
TI  - Electroconvulsive stimulations normalizes stress-induced changes in the
      glucocorticoid receptor and behaviour.
AB  - Animal models of chronic stress, such as 21 days of 6h/daily restraint stress
      cause changes in neuronal morphology in the hippocampus and alter behaviour.
      These changes are partly mediated by the glucocorticoids. The objective of this
      study was threefold: (1) to study how this particular chronic stress paradigm
      influences expression of hippocampal glucocorticoid receptor mRNA, (2) to study
      the effect of previous repeated restraint stress on the behaviours executed in
      the forced swim test (FST) (e.g. a novel inescapable stress situation) and (3) to
      investigate the modulating effect of electroconvulsive stimulations (ECS) on the
      neural and behavioural effects of the stress paradigm. The study shows that
      restraint stress lowered glucocorticoid receptor mRNA levels in all hippocampal
      regions, including the CA3 region which is the site of the characteristic
      dendritic reorganization seen in this model. Furthermore, stressed rats displayed
      higher increases in immobility and decreased latency to immobility subjected to
      the novel stressor of the FST than non-stressed rats. ECS abolished both the
      neural and behavioural effects of the restraint stress and thus protected against
      the deleterious effects of the stress paradigm. The clinical relevance of these
      findings is discussed.

PMID- 18725248
TI  - Temporal course of word recognition in skilled readers: a magnetoencephalography
      study.
AB  - The goal of the study was to investigate the neural circuit recruited by adult
      readers during performance of a lexical decision task by assessing the relative
      timing of neurophysiological activity in the brain regions that comprise this
      circuit. The time course of regional activation associated with lexical decision
      was studied in 17 adult volunteers using magnetoencephalography. Following
      activity in mesial occipital cortices, activation progressed to lateral and
      ventral occipito-temporal regions (often encompassing the posterior portion of
      the middle temporal gyrus), followed by activity in the superior temporal gyri
      (STGp), motor/premotor cortices, and the inferior frontal gyrus. The latency of
      STGp activation relative to the latency of the motor response to the word stimuli
      did not support critical involvement of this area in lexical decision. Timing,
      word length, and word frequency effects found for activity in each area are
      discussed in relation to the purported roles of each region into the brain
      circuit for reading.

PMID- 18725249
TI  - Joining the dots: production, processing and targeting of U snRNP to nuclear
      bodies.
AB  - The spliceosome is the RNP complex than catalyses the removal of introns from the
      Uridine-rich small nuclear ribonucleoproteins (U snRNPs) that make up the main
      components of this complex. The production of these RNPs is an intricate process,
      involving several key stages. These include: 1) the transcription of the U
      snRNAs; 2) their nuclear export; 3) the cytoplasmic assembly of the U snRNP; 4)
      their nuclear import; 5) their processing within Cajal bodies and the nucleolus;
      and 6) their storage in interchromatin granule clusters (IGCs). This review
      focuses on each of these stages, discussing the key complexes involved as well as
      the trafficking and targeting mechanisms involved.

PMID- 18725251
TI  - Gas chromatographic metabolic profiling: a sensitive tool for functional
      microbial ecology.
AB  - Microbial metabolomics, which consists of a non-targeted analysis of the
      metabolites released from ('exometabolome') or existing in ('endometabolome') a
      cell has mostly been used to study the metabolism of particular microbes.
      Metabolomes also represent a picture of microbial activity and we suggest that
      the exometabolome may also contain pertinent information for studying microbial
      interaction networks. Gas chromatography coupled to mass spectrometry is the most
      commonly used technique in metabolomics studies. It allows a wide range of
      metabolites to be detected but requires the derivatisation of compounds prior to
      detection. This type of non-targeted analysis can introduce biases to the
      detection and quantification of the different metabolites, particularly at the
      extraction and derivatisation steps. The aims of this study, therefore, were to
      quantify the sources of variability and to test the sensitivity of the GC
      metabolic profiling approach to small environmental changes such as shifts in
      temperature. The temperature sensitivity of metabolic profiles was compared with
      that of catabolic profiles obtained using Biolog microplates. Analytical
      variability was compared with biological variability by incubating bacterial
      strains isolated from soil with fructose at 20 degrees C and by replicating each
      step of the protocol (incubation, extraction and derivatisation). For both the
      endo- and the exometabolome, more than 70% of the total variability was of
      biological origin and principal components analysis clearly separated the strains
      along the first ordination axis. The endometabolome distinguished bacterial
      strains at the species level only, whereas separation was evident at the species
      and group level with the exometabolome. Temperature had a significant but
      differential effect on the metabolite production of the bacterial strains whilst
      their catabolic profiles remained relatively unaffected. The exometabolome was
      more sensitive to temperature shifts than the endometabolome, suggesting that
      this pool may be of interest for studies in environmental functional ecology.

PMID- 18725252
TI  - Facial affect manifested by multiple oscillations.
AB  - The present study describes electrophysiological differentiation of "Facial
      Expressions" by using the method of event-related oscillations (EROs). These
      measures were used to assess electrical manifestations of emotional expressions
      of 20 healthy subjects exposed to neutral, angry, and happy" faces. The present
      study extended previous analysis to frequency windows of delta (0.5-3.5 Hz) and
      theta (5-8.5 Hz) oscillations. No significant differences among responses to
      various face expression stimuli were observed, however, topological differences
      in response to all facial expressions were found. Delta oscillatory responses in
      the parietal-temporal-occipital locations were larger than the frontal and
      central locations, whereas theta oscillatory responses in the right temporal
      occipital electrodes were larger than the right central electrodes. Assessment of
      topologically distributed multiple oscillations opens a new avenue for
      understanding of the electrophysiology of recognition of "faces" and "facial
      expressions".

PMID- 18725250
TI  - Cellular functions of cardiolipin in yeast.
AB  - Cardiolipin (CL), the signature lipid of mitochondria, plays a critical role in
      mitochondrial function and biogenesis. The availability of yeast mutants blocked
      in CL synthesis has facilitated studies of the biological role of this lipid.
      Perturbation of CL synthesis leads to growth defects not only during respiratory
      growth but also under conditions in which respiration is not essential. CL was
      shown to play a role in mitochondrial protein import, cell wall biogenesis, aging
      and apoptosis, ceramide synthesis, and translation of electron transport chain
      components. The genetic disorder Barth syndrome (BTHS) is caused by mutations in
      the tafazzin gene resulting in decreased total CL levels, accumulation of
      monolysocardiolipin (MLCL), and decreased unsaturated fatty acyl species of CL.
      The variation in clinical presentation of BTHS indicates that other physiological
      factors play a significant role in modifying the phenotype resulting from
      tafazzin deficiency. Elucidating the functions of CL is expected to shed light on
      the role of this important lipid in BTHS and other disorders of mitochondrial
      dysfunction.

PMID- 18725253
TI  - Episodic memory decay along the adult lifespan: a review of behavioral and
      neurophysiological evidence.
AB  - The ability to learn and remember new information declines along life. Empirical
      evidence reveals that this deficit occurs unevenly with different types of
      memory. Episodic memory, which is referred to as the ability to remember our own
      experiences in a determined temporal and spatial context, is especially
      vulnerable to aging. Episodic information can be retrieved with or without the
      context information that took place when the episodic event was encoded. There is
      agreement that, with advancing age, the source information related to an episodic
      event is more susceptible to be forgotten than the event; however, there is no
      consensus regarding the age at which this decline begins, the speed of source
      memory decline along life or the possible changes, due to aging, in
      neurophysiological activity during encoding of source information that is
      subsequently correctly retrieved. In an attempt to answer the first two issues, a
      behavioral study with 552 subjects from 20 to 80 years of age was conducted,
      which provided evidence of the exact age at which source memory starts to decline
      and of the speed of this memory loss along life. To address the last question,
      event-related potentials were recorded while young and old adults encoded source
      information, to investigate whether older adults generate memory traces different
      from young adults during encoding.

PMID- 18725254
TI  - Are oscillatory brain responses generally reduced in schizophrenia during long
      sustained attentional processing?
AB  - Deficits in sustained attention and vigilance were assessed for oscillatory
      delta, theta, alpha, and gamma EEG activity during an auditory continuous
      performance task in patients with schizophrenia and healthy controls by
      quantifying peak-to-peak amplitudes of averaged and single-trial data. Averaged
      data indicated significantly reduced amplitudes in schizophrenia patients in all
      analyzed frequency bands, mainly at anterior locations. Single-trial analysis
      suggested that the amplitude reductions observed in the averaged delta, theta,
      and alpha response in patients originated from increased inter-trial phase
      variability. Gamma activity maximum amplitudes were reduced at the single-trial
      level. The findings imply that EEG activity in patients with schizophrenia can be
      characterized by multiple deficits in oscillatory networks, which indicates a
      disturbance in the temporal integration and interaction of all frequency
      components and their inter-trial variability.

PMID- 18725255
TI  - Modulation of the startle reflex by pleasant and unpleasant music.
AB  - The issue of emotional feelings to music is the object of a classic debate in
      music psychology. Emotivists argue that emotions are really felt in response to
      music, whereas cognitivists believe that music is only representative of
      emotions. Psychophysiological recordings of emotional feelings to music might
      help to resolve the debate, but past studies have failed to show clear and
      consistent differences between musical excerpts of different emotional valence.
      Here, we compared the effects of pleasant and unpleasant musical excerpts on the
      startle eye blink reflex and associated body markers (such as the corrugator and
      zygomatic activity, skin conductance level and heart rate). The startle eye blink
      amplitude was larger and its latency was shorter during unpleasant compared with
      pleasant music, suggesting that the defensive emotional system was indeed
      modulated by music. Corrugator activity was also enhanced during unpleasant
      music, whereas skin conductance level was higher for pleasant excerpts. The
      startle reflex was the response that contributed the most in distinguishing
      pleasant and unpleasant music. Taken together, these results provide strong
      evidence that emotions were felt in response to music, supporting the emotivist
      stance.

PMID- 18725256
TI  - Controlled release of active as a consequence of the die diameter in solid lipid
      extrusion.
AB  - The aim of the study was the investigation of dependency of the release profile
      on the original diameters of milled extrudates manufactured by solid lipid
      extrusion. Different die diameters in the range of 0.3 mm to 5.0 mm were used.
      The extrudates were milled and sieved. The fractions between 315 microm and 400
      microm were investigated within their shape, surface area and dissolution
      profiles by using the dissolution tester and the disintegration tester for short
      time dissolution tests. Different pH-media were used for the release tests: pH
      1.2 to imitate release conditions in the stomach and pH 7.4 to imitate conditions
      in the mouth. The chosen active enrofloxacin, a derivate of 3-quinolinecarboxylic
      acid, offers different solubilities in these release media. Two conclusions of
      this study were obtained: In the case of slightly solubility of active in the
      medium there was no dependency of the released active on the die diameter. If the
      active was very slightly soluble in the release medium a dependency between the
      two parameters was found. Having bad tasting actives like enrofloxacin, this
      achievement has an enormous impact on the manufacturing processes: a reduction of
      die diameters and therefore reduction of released amount of active will lead to
      taste masking.

PMID- 18725257
TI  - Solid-in-oil nanodispersion shows a possibility of transdermal protein delivery.

PMID- 18725258
TI  - P-glycoprotein (Abcb1) is involved in absorptive drug transport in skin.
AB  - The purpose of the present study was to investigate the role of P-glycoprotein (P
      gp) in drug disposition in skin. The distribution of P-gp substrates (rhodamine
      123 and itraconazole) to the skin after administration from the epidermal side
      was lower in P-gp gene knockout (mdr1a/1b(-/-)) mice than that in wild-type mice.
      Coadministration of propranolol, a P-gp inhibitor, decreased the distribution of
      itraconazole to the skin in wild-type mice, but not in mdr1a/1b(-/-) mice. These
      results suggest that P-gp contributes to the influx (from the epidermal side) of
      its substrates into skin, although P-gp is generally involved in efflux of drugs
      from various tissues. This finding was supported by the lower vectorial transport
      of rhodamine 123 from the epidermal to the hypodermal side in mdr1a/1b(-/-) mice
      in Ussing-type chamber experiments and by the immunohistochemical localization of
      P-gp throughout the dermal layer. Distribution of itraconazole after intravenous
      administration, on the other hand, was higher in mdr1a/1b(-/-) mice than that in
      wild-type mice, suggesting that P-gp transports this drug from the skin to the
      circulation. The present findings are the first to demonstrate involvement of P
      gp in dermal drug disposition.

PMID- 18725259
TI  - Homocysteine decreases blood flow to the brain due to vascular resistance in
      carotid artery.
AB  - An elevated level of Homocysteine (Hcy) is a risk factor for vascular dementia
      and stroke. Cysthathionine beta Synthase (CBS) gene is involved in the clearance
      of Hcy. Homozygous individuals for (CBS-/-) die early, but heterozygous for (CBS
      /+) survive with high levels of Hcy. The gamma-Amino Butyric Acid (GABA) presents
      in the central nervous system (CNS) and functions as an inhibitory
      neurotransmitter. Hcy competes with GABA at the GABA(A) receptor and affects the
      CNS function. We hypothesize that Hcy causes a decrease in blood flow to the
      brain due to increase in vascular resistance (VR) because of arterial remodeling
      in the carotid artery (CA). Blood pressure and blood flow in CA of wild type
      (WT), CBS-/+, CBS-/+ GABA(A)-/- double knockout, and GABA(A)-/- were measured. CA
      was stained with trichrome, and the brain permeability was measured. Matrix
      Metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase (TIMP
      3, TIMP-4), elastin, and collagen-III expression were measured by real-time
      polymerase chain reaction (RT-PCR). Results showed an increase in VR in CBS
      /+/GABA(A)-/-double knockout>CBS-/+/>GABA(A)-/- compared to WT mice. Increased
      MMP-2, MMP-9, collagen-III and TIMP-3 mRNA levels were found in GABA(A)-/-, CBS
      /+, CBS-/+/GABA(A) double knockout compared to WT. The levels of TIMP-4 and
      elastin were decreased, whereas the levels of MMP-2, MMP-9 and TIMP-3 increased,
      which indirectly reflected the arterial resistance. These results suggested that
      Hcy caused arterial remodeling in part, by increase in collagen/elastin ratio
      thereby increasing VR leading to the decrease in CA blood flow.

PMID- 18725260
TI  - Targeting subcapsular antigens for prevention of Klebsiella pneumoniae
      infections.
AB  - Vaccination strategies against Klebsiella pneumoniae have largely focussed on the
      polysaccharide capsule. However, the large number and high prevalence of
      individual capsular serotypes limits the widespread applicability of capsule
      based vaccines. This study establishes that immunization with purified LPS can
      protect mice against lethal challenge with K. pneumoniae, and that subcapsular
      antibodies directed against purified LPS can be used to treat and/or prevent
      experimental K. pneumoniae infection in mice. This approach offers potential for
      prophylaxis and/or therapy against drug-resistant strains of K. pneumoniae.

PMID- 18725261
TI  - The influence of CD4+ CD25+ Foxp3+ regulatory T cells on the immune response to
      rotavirus infection.
AB  - Rotavirus (RV) infection of the intestine is the major cause of severe
      dehydrating diarrhea in infants around the world. Although protective immunity
      against RV, especially acquired B and T-cell responses, has been extensively
      studied, our understanding of RV immunity remains incomplete. In addition, the
      interaction between various protective immune mechanisms in the gut and specific
      enteric immune suppressor systems that normally exert a regulatory function on
      mucosal immunity has not been extensively investigated. Among the candidate
      suppressor systems, we hypothesized that CD4+ CD25+ Foxp3+ regulatory T (Treg)
      cells may play a role in modulating RV immunity since such cells are naturally
      present in large numbers in the intestine and function nonspecifically. Here we
      demonstrate that neonatal murine RV (EC) infection induces an expansion of the
      Treg cell population and the magnitude of the T cell mediated immune response is
      modulated by Treg cells. Accordingly, when natural Treg cells in neonatal mice
      were depleted before virus infection, both CD4+ and CD8+ T-cell responses to RV,
      such as proliferation and IFN-gamma secretion, were enhanced in mesenteric lymph
      nodes (MLNs) and the spleen. Interestingly, increased proliferation of CD19+ B
      cells from Treg cell depleted animals was also observed. Finally, we analyzed the
      in vivo effect of the Treg cell depletion on diarrheal disease, virus shedding
      and IgA RV-specific response. Treg cell depletion did not affect these functions.
      Our studies of immune modulatory Treg cells in the RV infection model may promote
      a better understanding of the basis for RV immunity as well as providing valuable
      clues for the development of more immunogenic RV vaccines.

PMID- 18725262
TI  - Rebuttal to letter to the editor. Dr. Qin (Volume 51, 2008).

PMID- 18725263
TI  - Interaction between serotonin 5-HT1A receptors and beta-endorphins modulates
      antidepressant response.
AB  - Interactions between serotonergic and the endogenous opioid systems have been
      suggested to be involved in the etiopathogenesis of depression and in the
      mechanism of action of antidepressants. Activation of serotonin 5-HT1A receptors
      has been shown to increase plasma beta-endorphin (beta-END) levels in animal
      studies and in healthy humans. OBJECTIVES: To assess interaction abnormalities
      between 5-HT1A receptors and the endogenous opioid system in patients with major
      depression and the possible modulating effect of citalopram. METHODS: The beta
      END response to the 5-HT1A receptor agonist, buspirone (30 mg), was measured in
      30 patients with major depression and in 30 age- and sex-matched healthy controls
      before and after an 8-week treatment with citalopram. Pre-treatment score of the
      Hamilton Rating Scale for Depression (HRSD) was >or=17. Antidepressant response
      was defined by a 50% decrease in the HRSD. Pre- and post-treatment maximum peak
      response (Deltamax) and the area under the curve (AUC) of beta-END response were
      compared. Three time points were measured (60, 90 and 120 min). We also examined
      the correlations between the beta-END response and the antidepressant response.
      Buspirone plasma levels were not measured. RESULTS: At baseline, beta-END
      response was similar in patients and controls. After 8 weeks of citalopram
      treatment depressed patients showed a significant decrease in the beta-END
      response (Deltamax: p<.001; AUC: p<.001). A significant correlation between the
      beta-END reduction in the response and the reduction in the HRSD score (r=.656;
      p<.001) was observed. CONCLUSIONS: Changes in interaction between 5-HT1A receptor
      system and the endogenous opioid system may play a role both in the mechanism of
      action and response to antidepressant drugs.

PMID- 18725264
TI  - Medicinal properties of mangosteen (Garcinia mangostana).
AB  - Many tropical plants have interesting biological activities with potential
      therapeutic applications. Garcinia mangostana Linn. (GML) belongs to the family
      of Guttiferae and is named "the queen of fruits". It is cultivated in the
      tropical rainforest of some Southeast Asian nations like Indonesia, Malaysia, Sri
      Lanka, Philippines, and Thailand. People in these countries have used the
      pericarp (peel, rind, hull or ripe) of GML as a traditional medicine for the
      treatment of abdominal pain, diarrhea, dysentery, infected wound, suppuration,
      and chronic ulcer. Experimental studies have demonstrated that extracts of GML
      have antioxidant, antitumoral, antiallergic, anti-inflammatory, antibacterial,
      and antiviral activities. The pericarp of GML is a source of xanthones and other
      bioactive substances. Prenylated xanthones isolated from GML have been
      extensively studied; some members of these compounds possess antioxidant,
      antitumoral, antiallergic, anti-inflammatory, antibacterial, antifungal and
      antiviral properties. Xanthones have been isolated from pericarp, whole fruit,
      heartwood, and leaves. The most studied xanthones are alpha-, beta-, and gamma
      mangostins, garcinone E, 8-deoxygartanin, and gartanin. The aim of this review is
      to summarize findings of beneficial properties of GML's extracts and xanthones
      isolated from this plant so far.

PMID- 18725265
TI  - Characterization of three human sec14p-like proteins: alpha-tocopherol transport
      activity and expression pattern in tissues.
AB  - Three closely related human sec14p-like proteins (hTAP1, 2, and 3, or SEC14L2, 3,
      and 4, respectively) have been described. These proteins may participate in
      intracellular lipid transport (phospholipids, squalene, tocopherol analogues and
      derivatives) or influence regulatory lipid-dependent events. Here, we show that
      the three recombinant hTAP proteins associate with the Golgi apparatus and
      mitochondria, and enhance the in vitro transport of radioactively labeled alpha
      tocopherol to mitochondria in the same order of magnitude as the human alpha
      tocopherol transfer protein (alpha-TTP). hTAP1 and hTAP2 are expressed in several
      cell lines, whereas the expression level of hTAP3 is low. Expression of hTAP1 is
      induced in human umbilical cord blood-derived mast cells upon differentiation by
      interleukin 4. In tissues, the three hTAPs are detectable ubiquitously at low
      level; pronounced and localized expression is found for hTAP2 and hTAP3 in the
      perinuclear region in cerebellum, lung, liver and adrenal gland. hTAP3 is well
      expressed in the epithelial duct cells of several glands, in ovary in endothelial
      cells of small arteries as well as in granulosa and thecal cells, and in testis
      in Leydig cells. Thus, the three hTAPs may mediate lipid uptake, secretion,
      presentation, and sub-cellular localization in a tissue-specific manner, possibly
      using organelle- and enzyme-specific docking sites.

PMID- 18725266
TI  - Proteomic approach to the identification of novel delta-lactoferrin target genes:
      Characterization of DcpS, an mRNA scavenger decapping enzyme.
AB  - The expression of the transcription factor DeltaLf is deregulated in cancer
      cells. Its overexpression provokes cell cycle arrest along with antiproliferative
      effects and we recently showed that the Skp1 gene promoter was a target of
      DeltaLf. Skp1 belongs to the Skp1/Cullin-1/F-box ubiquitin ligase complex
      responsible for the ubiquitination and the proteosomal degradation of numerous
      cellular regulators. The transcriptional activity of DeltaLf is highly controlled
      and negatively regulated by O-GlcNAc, a dynamic post-translational modification
      known to regulate the functions of many intracellular proteins. We, therefore,
      constructed a DeltaLf-M4 mutant corresponding to a constitutively active DeltaLf
      isoform in which all the glycosylation sites were mutated. In order to discover
      novel targets of DeltaLf transcriptional activity and to investigate the impact
      of the O-GlcNAc regulation on this activity in situ we compared the proteome
      profiles of DeltaLf- and DeltaLf-M4-expressing HEK293 cells versus null plasmid
      transfected cells. A total of 14 differentially expressed proteins were
      visualized by 2D electrophoresis and silver staining and eight proteins were
      identified by mass spectrometry analyses (MALDI-TOF; LC-MS/MS), all of which were
      upregulated. The identified proteins are involved in several processes such as
      mRNA maturation and stability, cell viability, proteasomal degradation, protein
      and mRNA quality control. Among these proteins, only DcpS and TCPB were also
      upregulated at the mRNA level. Analysis of their respective promoters led to the
      detection of a cis-regulating element in the DcpS promoter. The S1(DcpS) is 80%
      identical to the S1 sequence previously described by He and Furmanski [Sequence
      specificity and transcriptional activation in the binding of lactoferrin to DNA,
      Nature 373 (1995) 721-724]. Reporter gene analyses and ChIP assays demonstrated
      that DeltaLf interacts specifically with the DcpS promoter in vivo. These data
      established that DcpS, a key enzyme in mRNA decay, is a new target of DeltaLf
      transcriptional activity.

PMID- 18725267
TI  - Thermodynamic characterization of the palm tree Roystonea regia peroxidase
      stability.
AB  - The structural stability of a peroxidase, a dimeric protein from royal palm tree
      (Roystonea regia) leaves, has been characterized by high-sensitivity differential
      scanning calorimetry, circular dichroism, steady-state tryptophan fluorescence
      and analytical ultracentifugation under different solvent conditions. It is shown
      that the thermal and chemical (using guanidine hydrochloride (Gdn-HCl))
      folding/unfolding of royal palm tree peroxidase (RPTP) at pH 7 is a reversible
      process involving a highly cooperative transition between the folded dimer and
      unfolded monomers, with a free stabilization energy of about 23 kcal per mol of
      monomer at 25 degrees C. The structural stability of RPTP is pH-dependent. At pH
      3, where ion pairs have disappeared due to protonation, the thermally induced
      denaturation of RPTP is irreversible and strongly dependent upon the scan rate,
      suggesting that this process is under kinetic control. Moreover, thermally
      induced transitions at this pH value are dependent on the protein concentration,
      allowing it to be concluded that in solution RPTP behaves as dimer, which
      undergoes thermal denaturation coupled with dissociation. Analysis of the kinetic
      parameters of RPTP denaturation at pH 3 was accomplished on the basis of the
      simple kinetic scheme N-->kD, where k is a first-order kinetic constant that
      changes with temperature, as given by the Arrhenius equation; N is the native
      state, and D is the denatured state, and thermodynamic information was obtained
      by extrapolation of the kinetic transition parameters to an infinite heating
      rate. Obtained in this way, the value of RPTP stability at 25 degrees C is ca. 8
      kcal per mole of monomer lower than at pH 7. In all probability, this quantity
      reflects the contribution of ion pair interactions to the structural stability of
      RPTP. From a comparison of the stability of RPTP with other plant peroxidases it
      is proposed that one of the main factors responsible for the unusually high
      stability of RPTP which enhances its potential use for biotechnological purposes,
      is its dimerization.

PMID- 18725268
TI  - Upregulation of matrix metalloproteinase-9 dependent on hyaluronan synthesis
      after sciatic nerve injury.
AB  - Using a rat chronic constriction injury (CCI) model, we analyzed the expression
      and activity of matrix metalloproteinase-9 (MMP-9) after sciatic nerve injury and
      its relationship with hyaluronan (HA). MMP-9 expression and activity were induced
      after the nerve injury. We found that CCI rats with oral administration of 4
      methylunbelliferone (4-MU), which was a hyaluronan synthases inhibitor, exhibited
      reduced MMP-9 activity and mRNA expression compared with CCI rats that were not
      given 4-MU. MMP modulatory factors, such as TIMPs and uPA, did not change after
      the 4-MU was administered. This result indicated that the upregulation of MMP-9
      after nerve injury in CCI rats was dependent on HA synthesis and was useful for
      the treatment of nerve injuries.

PMID- 18725269
TI  - Neural circuitry of play fighting in golden hamsters.
AB  - In hamsters, play fighting matures gradually into adult aggression. As these two
      behaviors share many similarities in this species, we predicted that a single
      neural circuitry controls their offensive component. The goal of the present
      study was to identify neural systems associated with offensive play fighting in
      male juvenile golden hamsters. The neural circuitry related to this behavior was
      identified through quantification of c-Fos immunolabeling. We also looked for
      vasopressin cells possibly associated with play fighting. We found that areas
      previously associated with offensive aggression in adult hamsters, including the
      ventrolateral hypothalamus, the medial amygdala, and the bed nucleus of the stria
      terminalis, also showed enhanced c-Fos expression after play fighting. In
      addition, vasopressin neurons in the nucleus circularis and the medial division
      of the supraoptic nucleus expressed enhanced c-Fos immunolabeling in juveniles
      after play fighting, as previously reported in adult hamsters after aggression.
      Finally, enhanced c-Fos expression associated with play fighting was also found
      in areas previously unexplored in adult hamsters, such as the prefrontal cortex.
      Together, our results support the hypothesis of a single core neural circuitry
      controlling the offensive components of play fighting and adult aggression
      throughout puberty in hamsters.

PMID- 18725270
TI  - Extracellular signal-regulated kinases mediate melittin-induced hypersensitivity
      of spinal neurons to chemical and thermal but not mechanical stimuli.
AB  - Subcutaneous melittin injection causes central plasticity at the spinal level in
      wide-dynamic-range (WDR) neurons, which are hypersensitive to various nociceptive
      stimuli. Previous behavioral studies demonstrated that the mitogen-activated
      protein kinases (MAPKs) extracellular signal-regulated kinase 1/2(ERK1/2), p38
      MAPK, and c-Jun N-terminal kinase are involved in both peripheral and spinal
      processing of melittin-induced nociception and hypersensitivity. Yet the
      functional roles of the three MAPKs vary among different stimulus modalities, and
      must be further studied at the cellular level in vivo. In this report,
      extracellular single unit recordings were performed to investigate whether
      activation of ERK1/2 in the primary injury site of melittin is essential to the
      establishment of a spinally sensitized state. Localized peripheral administration
      of a single dose of the MEK inhibitor U0126 (1 MUg/10 MUl) significantly
      suppressed neuronal hyper-responsiveness to thermal stimulus and chemical
      (melittin)-induced tonic firing of WDR neurons after full establishment of a
      spinally sensitized state. However, U0126 failed to affect mechanical
      hypersensitivity to both noxious and non-noxious stimuli. Melittin-induced
      enhancement of thermal hypersensitivity was also greatly inhibited by a single
      dose of capsazepine, a thermal nociceptor (TRPV1) blocker. These results suggest
      that activation of the ERK signaling pathway in the periphery is likely necessary
      for maintenance of a spinally sensitized state; activation of ERK1/2 in the
      primary injury site may regulate TRPV1, leading to dorsal horn hypersensitivity
      to thermal and chemical stimuli. ERK signaling pathways are not likely to be
      associated with melittin-induced dorsal horn hypersensitivity to mechanical
      stimuli.

PMID- 18725271
TI  - Cloning and functional analysis of the promoter region of the human Disc large
      gene.
AB  - A number of studies have demonstrated the involvement of human Disc large (DLG1)
      in the control of both cell polarity and maintenance of tissue architecture.
      However, the mechanisms controlling DLG1 transcription are not fully understood.
      This is relevant since DLG1 is lost in many tumours during the later stages of
      malignant progression. Therefore, we performed the cloning and functional
      analysis of a genomic 5' flanking region of the DLG1 open reading frame with
      promoter activity. We analyzed the activity of a series of 5' deletion constructs
      of the DLG1 promoter and determined the minimal essential sequences that are
      required for promoter activity as well as cis-elements that regulate
      transcription. We found, within the DLG1 promoter sequences, consensus-binding
      sites for the Snail family of transcription factors that repress the expression
      of epithelial markers and are up-regulated in a variety of tumours. Snail
      transcription factors repress the transcriptional activity of the DLG1 promoter
      and, ectopically expressed Snail proteins bind to the native DLG1 promoter. These
      data suggest a role for Snail transcription factors in the control of DLG1
      expression and provide a basis for understanding the transcriptional regulation
      of DLG1.

PMID- 18725273
TI  - A biochemical and genetic study of Leishmania donovani pyruvate kinase.
AB  - Here we present a biochemical and molecular biology study of the enzyme pyruvate
      kinase (PYK) from the parasitic protozoa Leishmania donovani. The PYK gene was
      cloned, mutagenised and over expressed and its kinetic parameters determined.
      Like in other kinetoplastids, L. donovani PYK is allosterically stimulated by the
      effector fructose 2,6 biphosphate and not by fructose 1,6 biphosphate. When the
      putative effector binding site of L. donovani PYK was mutagenised, we obtained
      two mutants with extreme kinetic behavior: Lys453Leu, which retained a sigmoidal
      kinetics and was little affected by the effector; and His480Gln, which deployed a
      hyperbolic kinetics that was not changed by the addition of the effector.
      Molecular Dynamics (MD) studies revealed that the mutations not only altered the
      effector binding site of L. donovani PYK but also changed the folding of its
      domain C.

PMID- 18725272
TI  - Estimates of natural selection due to protein tertiary structure inform the
      ancestry of biallelic loci.
AB  - We consider the inference of which of two alleles is ancestral when the alleles
      have a single nonsynonymous difference and when natural selection acts via
      protein tertiary structure. Whereas the probability that an allele is ancestral
      under neutrality is equal to its frequency, under selection this probability
      depends on allele frequency and on the magnitude and direction of selection
      pressure. Although allele frequencies can be well estimated from intraspecific
      data, small fitness differences have a large evolutionary impact but can be
      difficult to estimate with only intraspecific data. Methods for predicting
      aspects of phenotype from genotype can supplement intraspecific sequence data.
      Recently developed statistical techniques can assess effects of phenotypes, such
      as protein tertiary structure on molecular evolution. While these techniques were
      initially designed for comparing protein-coding genes from different species, the
      resulting interspecific inferences can be assigned population genetic
      interpretations to assess the effect of selection pressure, and we use them here
      along with intraspecific allele frequency data to estimate the probability that
      an allele is ancestral. We focus on 140 nonsynonymous single nucleotide
      polymorphisms of humans that are in proteins with known tertiary structures. We
      find that our technique for employing protein tertiary structure information
      yields some biologically plausible results but that it does not substantially
      improve the inference of ancestral human allele types.

PMID- 18725274
TI  - Two forms of secreted and thermostable luciferases from the marine copepod
      crustacean, Metridia pacifica.
AB  - We cloned two forms of the secreted and thermostable luciferase genes, MpLuc1 and
      MpLuc2, from the marine copepod, Metridia pacifica. The 840-bp MpLuc1 cDNA
      comprised a 630-bp open reading frame encoding a 210-amino acid polypeptide (22.7
      kDa). MpLuc1 had the closest homology with Metridia longa luciferase. The 753-bp
      MpLuc2 cDNA consisted of a 567-bp open reading frame (20.3 kDa), and it had the
      closest homology with Gaussia princeps luciferase. Single-specimen genomic PCR
      confirmed the presence of two luciferase genes in M. pacifica, and single
      specimen RT-PCR revealed that both luciferase mRNAs were expressed. Both MpLuc1
      and MpLuc2 (MpLucs) specifically reacted with the substrate coelenterazine
      producing identical bioluminescent spectra (lambdamax, 485 nm), but with
      different kinetics. Adding salt such as MgCl2 and CaCl2 to the reaction mixture
      significantly enhanced MpLuc1 and MpLuc2 activities. Wild-type MpLucs were
      remarkably thermostable; MpLuc1 retained about 60% of the original activity even
      after incubation at 90 degrees C for 30 min. MpLucs expressed in NIH-3T3 and HeLa
      cells were largely secreted into the culture medium. Continuous monitoring of
      secreted MpLuc1 driven by the c-fos promoter demonstrated the potential
      usefulness of MpLuc1 in nondisruptive reporter assays.

PMID- 18725275
TI  - The complete mitochondrial genome of Parafronurus youi (Insecta: Ephemeroptera)
      and phylogenetic position of the Ephemeroptera.
AB  - The first complete mitochondrial genome of a mayfly, Parafronurus youi
      (Arthropoda: Insecta: Pterygota: Ephemeroptera: Heptageniidae), was sequenced
      using a long PCR-based approach. The genome is a circular molecule of 15,481 bp
      in length, and encodes the set of 38 genes. Among them, 37 genes are found in
      other conservative insect mitochondrial genomes, and the 38(th) unique gene is
      trnM-like (trnM2). The duplication-random loss model can be used to explain one
      of the translocations at least. The A+T content of the control region is 57%, the
      lowest proportion detected so far in Hexapoda. Based on the nucleotide dataset
      and the corresponding amino acid dataset of 12 protein-coding genes, Bayesian
      inference and maximum likelihood analyses yielded stable support for the
      relationship of the three basal clades of winged insects as
      Ephemeroptera+(Odonata+Neoptera).

PMID- 18725276
TI  - Cyclosporine A loaded SLNs: evaluation of cellular uptake and corneal
      cytotoxicity.
AB  - Cyclosporine A (CsA) loaded solid lipid nanoparticles (SLNs) for topical
      ophthalmic applications were prepared by high shear homogenization and ultrasound
      method using Compritol 888 ATO, Poloxamer 188 and Tween 80, to investigate the
      cellular uptake of rabbit corneal epithelial cells (RCE) and to evaluate the
      cytotoxicity. The size of the optimized formulation was 225.9+/-5.5 nm with a
      polydispersity index of 0.253+/-0.05. The zeta potential and entrapment
      efficiency was detected as -16.9+/-0.7 mV and 95.6%, respectively. The CsA
      release was found to be enzyme (lipase/co-lipase complex) dependent. SLNs were
      sterilized at 110 and 121 degrees C. The cytotoxicity was evaluated in vitro by
      means of RCE cells and was higher at 121 degrees C sterilization temperature,
      probably due to a supposed leakage of Tween 80 following lipid re
      crystallization. The permeation and penetration of CsA across/into the corneal
      cells were evaluated using in vitro and ex vivo experiments. The cellular uptake
      was investigated by replacing CsA with the fluorescent dye Rhodamine B. The
      penetration enhancement properties were supported by confocal laser scanning
      microscopy analysis. The internalization of SLNs in cornea and in RCE cell lines
      was confirmed, pointing out the possibility of CsA targeting to the cornea.

PMID- 18725277
TI  - Semi-permeable nanocapsules of konjac glucomannan-chitosan for enzyme
      immobilization.
AB  - Carboxymethyl konjac glucomannan-chitosan (CKGM-CS) nanocapsules, spontaneously
      prepared under very mild conditions by electrostatic complexation, were used for
      immobilizing L-asparaginase. The matrix has semi-permeability to allow the
      substrate and product to pass through and to keep L-asparaginase in the matrix to
      prevent leaking. The cell-like hydrogel matrix was prepared in aqueous system
      without organic solvents and reagents. The process of the preparation does not
      denature the enzyme and the activity of the immobilized and native enzyme is very
      similar. The activity, stability, and characters of the enzyme-loaded
      nanocapsules were studied. The results indicated the immobilized enzyme has
      better stability and activity in contrast to the native enzyme. These studies may
      supply a new material for the immobilization of pH and temperature-sensitive
      enzyme.

PMID- 18725278
TI  - 'Buchu' -Agathosma betulina and Agathosma crenulata (Rutaceae): a review.
AB  - South Africa has offered the world two indigenous aromatic plants from which
      commercially important natural products have been developed: Pelargonium
      graveolens (and its hybrids) the source of geranium oil and Agathosma betulina,
      from which 'Buchu' oil is produced. Despite the historical use of 'Buchu' and the
      commercial interest developed around this coveted indigenous resource the
      (limited) research has not been coherently assembled. This overview aims to unite
      aspects on the botany, traditional and modern day uses, chemistry and
      pharmacological data on 'Buchu' which is undeniably one of South Africa's most
      renowned botanical assets.

PMID- 18725279
TI  - Traditional Chinese medicine for atopic eczema: PentaHerbs formula suppresses
      inflammatory mediators release from mast cells.
AB  - BACKGROUND: PentaHerbs formula (PHF) containing Cortex Moutan, root bark of
      Paeonia suffruticosa Andr. (Ranunculaceae), Cortex Phellodendri, bark of
      Phellodendron chinensis Schneid. (Rutaceae), Flos Lonicerae, flower of Lonicera
      japonica Thunb. (Capri-foliaceae), Herba Menthae, aerial part of Mentha
      haplocalyx Briq. (Labiatae) and Rhizoma Atractylodis, rhizome of Atractylodes
      lancea (Thunb.) DC. (Compositae) at the ratio of 2:2:2:1:2 was useful in the
      management of eczema. AIM OF THE STUDY: Since the mechanism of action of PHF is
      not known, we aimed to investigate the actions of PHF on mast cell activation.
      MATERIALS AND METHODS: Effects of aqueous extracts of PHF and individual
      component herb on mediator release from rat peritoneal mast cells (RPMCs) and
      cytokine production from HMC-1 were investigated. RESULTS: PHF, Cortex Moutan and
      Herba Menthae significantly attenuated histamine release and prostaglandin D(2)
      synthesis from RPMC activated by anti-IgE and compound 48/80 (p<0.05). While Flos
      Lonicerae and Rhizoma Atractylodis suppressed only mediator release from compound
      48/80 activated RPMC, Cortex Phellodendri potentiated only anti-IgE induced
      mediator release (p<0.05). However, with the exception of Cortex Moutan, PHF and
      the other four component herbs failed to affect cytokine production in HMC-1.
      CONCLUSIONS: Although individual herbs demonstrated different modulating effects
      on mast cells, inhibition of inflammatory mediator release from mast cells would
      contribute to the therapeutic efficacy of PHF.

PMID- 18725280
TI  - A historical, scientific and commercial perspective on the medicinal use of
      Pelargonium sidoides (Geraniaceae).
AB  - ETHNOPHARMACOLOGICAL CONTEXT: A detailed review of the ethnobotany and commercial
      history of Pelargonium sidoides is presented, together with a brief summary of
      pre-clinical and clinical scientific results that support the use of the plant in
      modern, evidence-based phytomedicines. The aim is to identify the main factors
      responsible for the success in product development. MATERIALS AND METHODS: The
      literature studied includes all modern scientific papers and also old documents
      and books that are no longer readily accessible. RESULTS: Available
      ethnobotanical information shows that several tuberous Pelargonium species
      (including Pelargonium sidoides) are important traditional medicines with a rich
      ethnobotanical history. A summary of the interesting history of the commercial
      development of Stevens' Cure or Umckaloabo in Europe is presented. Scientific
      evidence for the efficacy of the product, mainly as a treatment for acute
      bronchitis, is reviewed. These include numerous in vitro studies as well as 18
      clinical studies. The botanical identity of the plant and its complex mixture of
      coumarins and other chemical constituents are summarised. CONCLUSIONS: The use of
      Pelargonium stems or tubers for a variety of ailments (including the
      complications of dysentery) is an important but hitherto under-estimated part of
      traditional medicine in southern Africa. Key elements in the successful
      development of Pelargonium sidoides from a profound traditional remedy to a
      highly successful phytomedicine include the choice of species, a favourable cost
      benefit ratio, innovative marketing over many years, good scientific evidence of
      the botanical and chemical identity of the product and convincing proof of
      concept.

PMID- 18725281
TI  - Evaluation of selected tropical seaweeds for in vitro anti-trichomonal activity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Human parasitic infections are a serious problem
      in tropical and sub-tropical developing countries. Trichomoniasis, responsible
      for the annual infection of 180 million people, is a common sexually transmitted
      disease caused by the protozoan Trichomonas vaginalis. Traditionally seaweeds
      have been used in folk medicine by coastal people in Asia and the Caribbean to
      treat parasitic infections and are a valuable source of novel anti-trichomonals.
      AIM OF THE STUDY: In our search for therapeutical alternatives to anti-protozoal
      chemotherapy, we collected a selection of 25 tropical seaweeds (12 Rhodophyta, 5
      Phaeophyta and 8 Chlorophyta) from the coast of Yucatan (Mexico) in order to
      undertake ethnopharmacological and chemotaxonomic investigations. MATERIALS AND
      METHODS: Organic algal extracts were tested for their anti-trichomonal properties
      on the growth inhibition of Trichomonas vaginalis. The cytotoxicity of seaweed
      extracts on mammal cell lines was also assessed. RESULTS: The results indicated
      that 44% of the seaweeds studied had high to moderate anti-trichomonal activity.
      Lobophora variegata and Udotea conglutinata showed the maximal anti-trichomonal
      activity with IC(50) values of 1.39 and 1.66microg/ml, respectively, with good
      selectivity. CONCLUSIONS: Lobophora variegata and Udotea conglutinata
      demonstrated promising anti-trichomonal potential and have been selected for
      further bio-guided fractionation and isolation of active anti-trichomonal
      compounds.

PMID- 18725282
TI  - A new approach to study medicinal plants with tannins and flavonoids contents
      from the local knowledge.
AB  - AIM OF THE STUDY: The present work tested the power of different methodological
      strategies for identifying plants that could be interesting in terms of their
      phenolic compounds (especially flavonoids and tannins) by comparing a new index
      in which priority-determining criteria are based on the free-listing technique as
      well as on two randomized methods for choosing plants within an ethnodirected
      based approach. MATERIALS AND METHODS: The present study was undertaken in the
      rural area of the municipality of Altinho located in the central region of
      Pernambuco State, northeastern Brazil. The ethnobotanical survey was divided into
      three different stages. The first stage was a general survey of 101 individuals
      on the use and knowledge of medicinal plants within the community. During the
      second stage local specialists were selected on the basis of the quality and
      quantity of information they offered during the initial phase of the
      investigation. The third stage consisted of returning to the specialists a final
      time in order to apply the free-listing technique. We also assumed that a plant
      could demonstrate anti-inflammatory and healing effects even without the presence
      of the compounds of interest of this study. RESULTS: There is a strong
      association between tannin content and the effects popularly attributed to wound
      healing and anti-inflammatory plants. No relationships were observed between
      plants used by the community to treat inflammation or healing with their
      flavonoid contents. CONCLUSION: Thus, identifying Caatinga medicinal plants known
      with anti-inflammatory activity and healing capacities is a good criterion for
      identifying species with high levels of tannins, although these same criteria are
      not useful for identifying plants with high flavonoid contents.

PMID- 18725283
TI  - Effects of compounds from Kaempferia parviflora on nitric oxide, prostaglandin E2
      and tumor necrosis factor-alpha productions in RAW264.7 macrophage cells.
AB  - Kaempferia parviflora Wall. ex Baker, is one of the plants in the Zingiberaceae
      family, locally known in Thai as kra-chai-dam. The rhizome of this plant has been
      used for treatment of gout, apthous ulcer and abscesses. Since K. parviflora
      rhizomes have long been used for treatment of inflammation and possessed marked
      nitric oxide (NO) inhibitory activity (IC(50)=7.8microg/ml), we thus investigated
      the inhibitory activity of compounds isolated from this plant against
      lipopolysaccharide (LPS)-induced NO release in RAW264.7 cells. From bioassay
      guided fractionation of K. parviflora, seven methoxyflavones were isolated from
      the hexane fraction and were tested for their anti-inflammatory effects. Among
      the isolated compounds, compound 5 (5-hydroxy-3,7,3',4'-tetramethoxyflavone)
      exhibited the highest activity against NO release with an IC(50) value of
      16.1microM, followed by 4 (IC(50)=24.5microM) and 3 (IC(50)=30.6microM). Compound
      5 was also tested on LPS-induced prostaglandin E(2) (PGE(2)) and tumor necrosis
      factor-alpha (TNF-alpha) releases from RAW264.7 cells. It was revealed that 5
      showed appreciable inhibitory effect on PGE(2) release (IC(50)=16.3microM), but
      inactive on TNF-alpha (IC(50)>100microM). These findings may support the use in
      Thai traditional medicine of K. parviflora for treatment of inflammatory-related
      diseases through the inhibition of NO and PGE(2) releases but partly due to that
      of TNF-alpha.

PMID- 18725284
TI  - Emerging high-throughput approaches to analyze bioremediation of sites
      contaminated with hazardous and/or recalcitrant wastes.
AB  - Sustainable development requires the promotion of environmental management and a
      constant search for new technologies to treat a wide range of aquatic and
      terrestrial habitats contaminated by increasing anthropogenic activities.
      Bioremediation, i.e. the elimination of natural or xenobiotic pollutants by
      living organisms, is an environmentally friendly and cost-effective alternative
      to physico-chemical cleanup options. However, the strategy and outcome of
      bioremediation in open systems or confined environments depend on a variety of
      physico-chemical and biological factors that need to be assessed and monitored.
      In particular, microorganisms are key players in bioremediation applications, yet
      their catabolic potential and their dynamics in situ remain poorly characterized.
      To perform a comprehensive assessment of the biodegradative potential of a
      contaminated site and efficiently monitor changes in the structure and activities
      of microbial communities involved in bioremediation processes, sensitive, fast
      and large-scale methods are needed. Over the last few years, the scientific
      literature has revealed the progressive emergence of genomic high-throughput
      technologies in environmental microbiology and biotechnology. In this review, we
      discuss various high--throughput techniques and their possible--or already
      demonstrated-application to assess biotreatment of contaminated environments.

PMID- 18725285
TI  - Influence of age and movement complexity on kinematic hand movement parameters in
      childhood and adolescence.
AB  - Development of fine motor functions, especially drawing and handwriting, are
      crucial for performance in school, autonomy in everyday life and the general
      human development. A variety of neurological and psychiatric conditions in
      childhood and adolescence stunt the normal development of fine motor skills. We
      sought to define the normal development of the kinematic parameters of fine motor
      movement and determine the influence of gender, laterality of handedness and
      extracurricular training on fine motor skills. One hundred and eighty-seven
      children and adolescents (mean age: 11.6 years (+/-S.D.: 3.58), range: 6-18
      years) were included in the study. Participants performed drawing and handwriting
      tasks on a digitizing graphic tablet. Movement and pressure data were transferred
      to a computer using a sensor-equipped pen and post-processed using CSWIN.
      Movements were segmented into strokes and several kinematic parameters were
      calculated. The kinematic parameters that were analyzed represented speed
      (frequency and stroke peak velocity), automation (number of direction changes of
      velocity per stroke), variability (variation coefficient of stroke peak velocity)
      and pressure. Progression of kinematic parameters for each movement domain of the
      handwriting and circle drawing tasks correlated significantly with age (Pearson's
      correlation, p<0.003). Speed, automation and pressure increased with age, whereas
      variability decreased. Nonlinear regressions revealed maturation of hand
      movements at a certain age. Age of completed maturation depended on the task
      complexity (drawing circles vs. handwriting) and kinematic parameters. In the
      speed and automation domains, handwriting movements finish maturing later than
      circle drawing. Male subjects drew circles at significantly higher speeds than
      female subjects. Fine motor practice and laterality of handedness did not
      influence kinematic parameters. A repeated measure ANOVA confirmed the
      significant interdependency between age and complexity level for speed and
      automation (p<0.001). The digitizing graphic tablet is an extremely valuable tool
      in determining the normal development of hand movement skills of children and
      adolescents by measuring relevant daily tasks like handwriting and drawing. In
      our study, we showed that future analyses of impaired movement in children and
      adolescents need to take age and gender into consideration. Furthermore,
      differences were observed in the maturation of different task complexities, the
      complex fine motor function reaching maturity later than basic and repetitive
      movement patterns.

PMID- 18725286
TI  - High-resolution melting curve analysis for genotyping of common SNP in MTHFR gene
      using fixed-cell suspension.
AB  - Genetic variation in MTHFR might explain the interindividual differences in both
      therapeutic and toxic responses to the treatment of cancer and rheumatoid
      arthritis with methotrexate, and can be involved in the sensitivity of developing
      diseases like cancer and congenital anomalies. We investigated the common
      sequence variation, C677T, in the MTHFR gene in fixed-cell specimens archived
      after chromosomal analysis using a novel gene scanning method based on post PCR
      analysis of high-resolution melting curves (HRM). These fixed specimens were
      stored after routine chromosomal analysis for 1 year at -20 degrees C in a 3:1
      methanol:acetic acid solution. The method revealed a distinct pattern between
      homozygous and heterozygous alleles. Sensitivity and specificity of the HRM based
      method were comparable to that obtained by a hybridization probe. While the
      success rate for genotyping of a common SNP in MTHFR was similar to the
      hybridization probe approach, the HRM based method was more cost-effective and
      had a shorter turnaround time.

PMID- 18725287
TI  - Zincergic innervation from the anterior olfactory nucleus to the olfactory bulb
      displays plastic responses after mitral cell loss.
AB  - Zinc ions are selectively accumulated in certain neurons (zinc-enriched neurons).
      The mouse olfactory bulb is richly innervated by zinc-enriched terminals. Here,
      the plasticity of the zincergic system was studied in the olfactory bulb of the
      Purkinje Cell Degeneration mutant mouse, an animal with specific postnatal
      neurodegeneration of the main projection neurons of the olfactory bulb. The
      analysis focused particularly on the anterior olfactory nucleus since most
      centrifugal afferents coming to the olfactory bulb arise from this structure.
      Zinc-enriched terminals in the olfactory bulb and zinc-enriched somata in the
      anterior olfactory nucleus were visualized after selenite injections.
      Immunohistochemistry against the vesicular zinc transporter was also carried out
      to confirm the distribution pattern of zinc-enriched terminals in the olfactory
      bulb. The mutant mice showed a clear reorganization of zincergic centrifugal
      projections from the anterior olfactory nucleus to the olfactory bulb. First, all
      zincergic contralateral neurons projecting to the olfactory bulb were absent in
      the mutant mice. Second, a significant increase in the number of stained somata
      was detected in the ipsilateral anterior olfactory nucleus. Since no noticeable
      changes were observed in the zinc-enriched terminals in the olfactory bulb, it is
      conceivable that mitral cell loss could induce a reorganization of zinc-enriched
      projections coming from the anterior olfactory nucleus, probably directed at
      balancing the global zincergic centrifugal modulation. These results show that
      zincergic anterior olfactory nucleus cells projecting to the olfactory bulb
      undergo plastic changes to adapt to the loss of mitral cells in the olfactory
      bulb of Purkinje Cell Degeneration mutant mice.

PMID- 18725288
TI  - Dimethoxyaurones: Potent inhibitors of ABCG2 (breast cancer resistance protein).
AB  - A series of 4,6-dimethoxyaurones were synthesized by reacting 4,6
      dimethoxybenzofuran-3(2H)-one with various benzaldehydes in a base-catalyzed
      aldol reaction. A Z configuration was assigned to the aurones based on
      spectroscopic and crystallographic data. The aurones were tested for their
      ability to modulate ABCG2 (breast cancer resistance protein)-mediated multidrug
      resistance in vitro. Several members (0.5 microM) increased the accumulation of
      mitoxantrone (MX) in human breast cancer cells (MDA-MB-231) transfected with
      ABCG2 and re-sensitized these cells to the cytotoxic effects of MX. In the re
      sensitization assay, aurones at 0.5 microM reduced the resistance of the
      transfected cells to MX to just twice that of the parental cells, exceeding
      fumitremorgin C (FTC) tested at the same concentration. The aurones (10 microM)
      also increased calcein-AM accumulation in MDCKII/MDR1 cells that were transfected
      with ABCB1 (P-glycoprotein), at levels comparable to verapamil tested at the same
      concentration. Structure-activity analysis showed that substitution of the
      benzylidene ring B of the aurone template was less important for ABCG2
      inhibition, with little variation in activity noted for compounds with an
      unsubstituted ring B or one that was substituted. In contrast, substitution of
      ring B gave rise to better inhibitors of ABCB1. A preference for the 3' position
      of ring B was noted. There was also some indication from the data that aurones
      with good ABCG2 inhibitory activity were poor ABCB1 inhibitors and vice versa,
      but further confirmation would be required. Limited antiproliferative activity
      (>70% cell survival) was observed for many aurones on four different cell lines.
      Thus, functionalized 4,6-dimethoxyaurones are promising ABCG2 inhibitors that
      combine good activity at submicromolar concentrations with limited
      antiproliferative activity.

PMID- 18725289
TI  - De novo biosynthetic pathways: rational design of microbial chemical factories.
AB  - Increasing interest in the production of organic compounds from non-petroleum
      derived feedstocks, especially biomass, is a significant driver for the
      construction of new recombinant microorganisms for this purpose. As a discipline,
      Metabolic Engineering has provided a framework for the development of such
      systems. Efforts have traditionally been focused, first, on the optimization of
      natural producers, later progressing towards re-construction of natural pathways
      in heterologous hosts. To maximize the potential of microbes for biosynthetic
      purposes, new tools and methodologies within Metabolic Engineering are needed for
      the proposition and construction of de novo designed pathways. This review will
      focus on recent advances towards the design and assembly of biosynthetic
      pathways, and provide a Synthetic Biology perspective for the construction of
      microbial chemical factories.

PMID- 18725290
TI  - Engineering the spatial organization of metabolic enzymes: mimicking nature's
      synergy.
AB  - A growing body of evidence indicates that many cellular reactions within
      metabolic pathways are catalyzed not by free-floating 'soluble' enzymes, but via
      one or more membrane-associated multienzyme complexes. This type of
      macromolecular organization has important implications for the overall
      efficiency, specificity, and regulation of metabolic pathways. An ever-increasing
      number of biochemical and genetic studies on primary and secondary metabolism
      have laid a solid foundation for this model, providing compelling evidence in
      favor of the so-called channeling of intermediates between enzyme active sites
      and colocalization of enzymes inside a cell. In this review, we discuss several
      of nature's most notable multifunctional enzyme systems including the AROM
      complex and tryptophan synthase, each of which provides new fundamental insights
      into the structural organization of metabolic machinery within living cells. We
      then focus on the growing body of literature related to engineering strategies
      using protein chimeras and post-translational assembly mechanisms. Common among
      these techniques is the desire to mimic natural enzyme organization for
      optimizing the production of valuable metabolites with industrial and medical
      importance.

PMID- 18725291
TI  - Mimicking stem cell niches to increase stem cell expansion.
AB  - Niches regulate lineage-specific stem cell self-renewal versus differentiation in
      vivo and are composed of supportive cells and extracellular matrix components
      arranged in a three-dimensional topography of controlled stiffness in the
      presence of oxygen and growth factor gradients. Mimicking stem cell niches in a
      defined manner will facilitate production of the large numbers of stem cells
      needed to realize the promise of regenerative medicine and gene therapy. Progress
      has been made in mimicking components of the niche. Immobilizing cell-associated
      Notch ligands increased the self-renewal of hematopoietic (blood) stem cells.
      Culture on a fibrous scaffold that mimics basement membrane texture increased the
      expansion of hematopoietic and embryonic stem cells. Finally, researchers have
      created intricate patterns of cell-binding domains and complex oxygen gradients.

PMID- 18725292
TI  - Feast or famine: autophagy control and engineering in eukaryotic cell culture.
AB  - Autophagy is a degradative process playing a role in both cell death and cell
      survival. Its presence is well conserved both in lower and higher eukaryotes.
      Recent studies have shown that activation or inhibition of autophagy may be
      possible in biotechnologically important species including mammalian cells and
      filamentous fungi using both environmental manipulation and genetic engineering.
      As our understanding of the autophagic biochemical pathways increases and
      monitoring methods become more user-friendly, the potential exists to obtain an
      optimum level of autophagy. This may allow for maximum cell survival and
      production of proteins and other metabolites in these industrially important
      eukaryotes.

PMID- 18725294
TI  - Microinjection as a tool of mechanical delivery.
AB  - Microinjection to single cells has been widely used in the studies of
      transduction-challenged cells, transgenic animal production, and in vitro
      fertilization to mechanically transfer DNAs, RNA interferences, sperms, proteins,
      peptides, and drugs. The advantages of microinjection include the precision of
      delivery dosage and timing, high efficiency of transduction as well as low
      cytotoxicity. However, manual microinjection is labor intensive and time
      consuming, which limits the application of this technique to large number of
      cells in a sample. New cell culture matrix ensuring all cells grow in a desired
      position and orientation is needed for application of high throughput automatic
      injection systems, which will significantly increase injection speed, cell
      survival, and success rates.

PMID- 18725293
TI  - Gene module level analysis: identification to networks and dynamics.
AB  - Nature exhibits modular design in biological systems. Gene module level analysis
      is based on this module concept, aiming to understand biological network design
      and systems behavior in disease and development by emphasizing on modules of
      genes rather than individual genes. Module level analysis has been extensively
      applied in genome wide level analysis, exploring the organization of biological
      systems from identifying modules to reconstructing module networks and analyzing
      module dynamics. Such module level perspective provides a high level
      representation of the regulatory scenario and design of biological systems,
      promising to revolutionize our view of systems biology, genetic engineering as
      well as disease mechanisms and molecular medicine.

PMID- 18725295
TI  - A green light for engineered algae: redirecting metabolism to fuel a
      biotechnology revolution.
AB  - Microalgae have the potential to revolutionize biotechnology in a number of areas
      including nutrition, aquaculture, pharmaceuticals, and biofuels. Although algae
      have been commercially cultivated for over 50 years, metabolic engineering now
      seems necessary in order to achieve their full processing capabilities. Recently,
      the development of a number of transgenic algal strains boasting recombinant
      protein expression, engineered photosynthesis, and enhanced metabolism encourage
      the prospects of designer microalgae. Given the vast contributions that these
      solar-powered, carbon dioxide-sequestering organisms can provide to current
      global markets and the environment, an intensified focus on microalgal
      biotechnology is warranted. Ongoing advances in cultivation techniques coupled
      with genetic manipulation of crucial metabolic networks will further promote
      microalgae as an attractive platform for the production of numerous high-value
      compounds.

PMID- 18725296
TI  - Signaling by death receptors in the nervous system.
AB  - Cell death plays an important role both in shaping the developing nervous system
      and in neurological disease and traumatic injury. In spite of their name, death
      receptors can trigger either cell death or survival and growth. Recent studies
      implicate five death receptors--Fas/CD95, TNFR1 (tumor necrosis factor receptor
      1), p75NTR (p75 neurotrophin receptor), DR4, and DR5 (death receptors-4 and -5)-
      in different aspects of neural development or degeneration. Their roles may be
      neuroprotective in models of Parkinson's disease, or pro-apoptotic in ALS and
      stroke. Such different outcomes probably reflect the diversity of transcriptional
      and posttranslational signaling pathways downstream of death receptors in neurons
      and glia.

PMID- 18725297
TI  - Signaling by synaptogenic molecules.
AB  - Multiple signaling pathways initiate and specify the formation of synapses in the
      central nervous system. General principles that organize nascent synapses have
      emerged from the studies in multiple model organisms. These include the synapse
      organizing roles of dedicated synaptic adhesion molecules, synaptic signaling
      following receptor-ligand interactions, and the regulation of synapse formation
      by secreted molecules. Intracellularly, a range of effectors subsequently
      regulates signaling steps and cytoskeletal changes. Together, a blueprint of
      synapse formation is emerging into which these distinct signaling steps will need
      to be integrated temporally and spatially.

PMID- 18725298
TI  - Components of the NGF signaling complex are altered in mdx mouse superior
      cervical ganglion and its target organs.
AB  - We previously reported that in the superior cervical ganglion (SCG) of dystrophic
      mdx mice, which lack full-length dystrophin, there is a loss of neurons
      projecting to SCG muscular targets, like the iris. Nonetheless, surviving
      neurons, innervating either iris or submandibular gland (SuGl), a SCG non
      muscular target, underwent reduced axon defasciculation and terminal branching.
      Here we report that, during early post-natal development, levels of pro-apoptotic
      proNGF in mdx mouse iris, but not in the SuGl, are higher than in the wild-type.
      This increase, along with reduced levels of NGF receptors (TrkA and p75NTR) in
      SCG, may be partly responsible for the observed loss of neurons projecting to the
      iris. These alterations, combined with a reduction in polysialylated-NCAM and
      neurofilament protein levels in SCG, may also account for reduced axon
      defasciculation and terminal branching in mdx mouse SCG targets.

PMID- 18725299
TI  - Gene expression analysis defines differences between region-specific GABAergic
      neurons.
AB  - Gamma-aminobutyric acid (GABA)ergic neurons are a diverse group of inhibitory
      neurons playing crucial roles in information processing. We analyzed the gene
      expression of regionally defined GABAergic neurons from the cortex, olfactory
      bulb, striatum, and cerebellum of glutamate decarboxylase 67-green fluorescence
      protein (GAD67-GFP) knock-in mice. We introduce a generally applicable method for
      singularization of brain cells, flow cytometric enrichment, and global mRNA
      amplification for sensitive gene expression profiling. Systematic quantification
      elicited a high dynamic range of GABAergic cell numbers in different brain
      regions. Clustering of our gene expression results revealed major differences
      between hind and forebrain GABAergic neurons indicating that the development of
      GABAergic neurons depends on their regional location. While GABAergic neurons of
      the forebrain are characterized by three main groups of transcription factors of
      the Distal-less-family, the POU-family, and ETS/FOX family, specific members of
      the ZIC- and LHX-family of transcription factors appear to define hindbrain
      inhibitory neurons.

PMID- 18725300
TI  - Opioids modulate pain facilitation from the dorsal reticular nucleus.
AB  - During chronic pain, the supraspinal pain modulatory system undergoes plastic
      changes with enhancement of facilitation transmission at the spinal cord. The
      changes induced by chronic pain at descending modulation often affect opioidergic
      modulation, and were never described for a key facilitatory component of the
      system, the dorsal reticular nucleus (DRt). Neurochemical characterization of the
      DRt-spinal pathway showed that delta-opioid receptors are positioned as to
      indirectly modulate the activity of non-projecting DRt neurons, whereas neurons
      expressing mu-opioid receptors project to the spinal dorsal horn or act as
      interneurons, the latter of which co-expressing GABA(B) receptors. In
      monoarthritic rats, the expression of mu-opioid receptors decreased in the DRt
      whereas the levels of endogenous enkephalin remained unaltered. To increase the
      opioidergic inhibition of the DRt, we locally injected selective agonists of
      delta- and mu-opioid receptors or a viral vector containing the human
      preproenkephalin transgene. Injection of the Herpes Simplex viral vector encoding
      preproenkephalin induced thermal hypoalgesia in non-inflamed animals and
      hyperalgesia in monoarthritic rats. The opioid agonists [D-Ala(2), Glu(4)]
      deltorphin (DELT) and [D-Ala(2), NMePhe(4)Gly-ol(5)]-enkephalin (DAMGO) induced
      thermal hyperalgesia in both non-inflamed and monoarthritic rats, but with lower
      doses in the latter group. The present study shows that opioidergic neurons at
      the DRt are modulated by GABAergic cells herein controlling the descending
      facilitation of pain transmission. The DRt exhibits plastic changes during
      chronic inflammatory pain, with decrease opioid receptor expression which may
      account for increased descending facilitation during chronic pain.

PMID- 18725301
TI  - A simple novel method for the preparation of noncovalent homodimeric,
      biologically active human interleukin 10 in Escherichia coli-enhancing protein
      expression by degenerate PCR of 5' DNA in the open reading frame.
AB  - DNA inserts encoding human interleukin 10 (hIL-10), optimized for codon usage and
      secondary RNA structure, were purchased from several commercial sources and
      subcloned into a pMon vector. Despite the optimization, protein expression was
      nil. We therefore subjected the 5' segment of the cDNA encoding N-terminal amino
      acids 2-11 to degenerate PCR in order to create a small library of 130K
      theoretical cDNA combinations that would not change the respective amino acid
      sequence and tested their expression. After screening over 320 colonies 10 hIL-10
      clones encoding the original amino acid sequence were identified. Three
      nucleotide substitutions were sufficient to ensure reasonable protein expression.
      Subsequently, hIL-10 was expressed in Escherichia coli, refolded and purified to
      homogeneity, yielding over 95% electrophoretically pure noncovalent homodimeric
      protein, which was biologically active in MC/9 cells. The yield of recombinant
      hIL-10 from 10L of fermentation culture was 60mg and a protocol for its long-term
      storage as a carrier-free lyophilized powder at -20 degrees was developed.

PMID- 18725302
TI  - Expression of a Trichoderma reesei beta-xylanase gene in Escherichia coli and
      activity of the enzyme on fiber-bound substrates.
AB  - A recombinant gene Xyn2 (570bp) encoding the main Trichoderma reesei Rut C-30
      endo-beta-1,4-xylanase was successfully cloned and expressed in Escherichia coli
      BL21 under the control of strong bacteriophage T7 transcription and translation
      signals. The molecular weight of the recombinant protein was estimated by SDS
      PAGE to be 24 kDa. The expressed protein was purified by Ni(2+)-NTA affinity
      chromatography and enzyme activity assay verified the protein as a xylanase. Like
      with the T. reesei Xyn2, the optimal activity of the recombinant Xyn2 was at 50
      degrees C. However, the recombinant xylanase had an improved thermostability and
      more than 70% of its activity remained after 30 min incubation at 60 degrees C.
      In addition, the recombinant xylanase was active over the range of pH 3.5-7.5
      with maximum activity at pH 5.0. The enzyme was highly specific towards xylans
      but exhibited very low activities towards cellulosic substrates. Using Birchwood
      xylan, the determined apparent K(m) and k(cat) values were 0.11 mg/ml and 106 s(
      1), respectively. These properties should make the enzyme an attractive candidate
      for various industrial applications.

PMID- 18725303
TI  - Expression of Candida antarctica lipase B in Pichia pastoris and various
      Escherichia coli systems.
AB  - Candida antarctica lipase B (CALB) carrying a point mutation, N74S, resulting in
      a non-glycosylated protein was actively expressed in Pichia pastoris yielding 44
      mg/L which was similar to that of the glycosylated CALB wild type expressed in P.
      pastoris. Hence, the major obstacle in the Escherichia coli expression of CALB is
      not the lack of glycosylation. To understand and improve the expression of CALB
      in E. coli, a comprehensive investigation of four different systems were tested:
      periplasmic expression in Rosetta (DE3), cytosolic expression in Rosetta-gami
      2(DE3) and Origami 2(DE3) as well as co-expression with chaperones groES and
      groEL in Origami B(DE3), all using the pET-22b(+) vector and the T7lac promoter.
      Furthermore the E. coli expression was carried out at three different
      temperatures (16, 25 and 37 degrees C) to optimise the expression. Periplasmic
      expression resulted in highest amount of active CALB of the four systems,
      yielding a maximum of 5.2mg/L culture at 16 degrees C, which is an improvement to
      previous reports. The specific activity of CALB towards tributyrin in E. coli was
      found to be the same for periplasmic and cytosolic expression. Active site
      titration showed that the CALB mutant N74S had a lower specific activity in
      comparison to wild type CALB regardless of expression host. The expected protein
      identity was confirmed by LC-ESI-MS analysis in E. coli, whereas in P. pastoris
      produced CALB carried four additional amino acids from an incomplete protein
      processing.

PMID- 18725304
TI  - Improved specimen reconstruction by Hilbert phase contrast tomography.
AB  - The low signal-to-noise ratio (SNR) in images of unstained specimens recorded
      with conventional defocus phase contrast makes it difficult to interpret 3D
      volumes obtained by electron tomography (ET). The high defocus applied for
      conventional tilt series generates some phase contrast but leads to an incomplete
      transfer of object information. For tomography of biological weak-phase objects,
      optimal image contrast and subsequently an optimized SNR are essential for the
      reconstruction of details such as macromolecular assemblies at molecular
      resolution. The problem of low contrast can be partially solved by applying a
      Hilbert phase plate positioned in the back focal plane (BFP) of the objective
      lens while recording images in Gaussian focus. Images recorded with the Hilbert
      phase plate provide optimized positive phase contrast at low spatial frequencies,
      and the contrast transfer in principle extends to the information limit of the
      microscope. The antisymmetric Hilbert phase contrast (HPC) can be numerically
      converted into isotropic contrast, which is equivalent to the contrast obtained
      by a Zernike phase plate. Thus, in-focus HPC provides optimal structure factor
      information without limiting effects of the transfer function. In this article,
      we present the first electron tomograms of biological specimens reconstructed
      from Hilbert phase plate image series. We outline the technical implementation of
      the phase plate and demonstrate that the technique is routinely applicable for
      tomography. A comparison between conventional defocus tomograms and in-focus HPC
      volumes shows an enhanced SNR and an improved specimen visibility for in-focus
      Hilbert tomography.

PMID- 18725305
TI  - Phylogenetic relationships of Middle American cichlids (Cichlidae, Heroini) based
      on combined evidence from nuclear genes, mtDNA, and morphology.
AB  - Heroine cichlids are the second largest and very diverse tribe of Neotropical
      cichlids, and the only cichlid group that inhabits Mesoamerica. The taxonomy of
      heroines is complex because monophyly of most genera has never been demonstrated,
      and many species groups are without applicable generic names after their removal
      from the catch-all genus Cichlasoma (sensu Regan, 1905). Hence, a robust
      phylogeny for the group is largely wanting. A rather complete heroine phylogeny
      based on cytb sequence data is available [Concheiro Perez, G.A., Rican O., Orti
      G., Bermingham, E., Doadrio, I., Zardoya, R. 2007. Phylogeny and biogeography of
      91 species of heroine cichlids (Teleostei: Cichlidae) based on sequences of the
      cytochrome b gene. Mol. Phylogenet. Evol. 43, 91-110], and in the present study,
      we have added and analyzed independent data sets (nuclear and morphological) to
      further confirm and strengthen the cytb-phylogenetic hypothesis. We have analyzed
      a combined cytb-nuclear (RAG1 and two S7 introns) data set of 48 species
      representing main heroine lineages to achieve further resolution of heroine
      higher taxonomic levels and a combined cytb-morphological data set of 92 species
      to stabilize generic taxonomy. The recovered phylogenies supported the
      circumamazonian--CAM--Heroini (sensu Concheiro Perez et al., 2007) as a
      monophyletic group, that could be divided into six main clades: (1)
      australoheroines (the southernmost heroine genus Australoheros), (2) nandopsines
      (the Antillean genus Nandopsis), (3) caquetaines (including the north western
      Amazonian genera Caquetaia and Heroina), (4) astatheroines (including Astatheros,
      Herotilapia and Rocio), (5) amphilophines (including Amphilophus and related
      genera), and (6) herichthyines (including Herichthyis and related genera).
      Nuclear and mitochondrial data partitions arrived at highly congruent topologies.
      Suprageneric relationships were influenced mainly by the nuclear signal, as well
      as the most basal phylogenetic position of Australoheros within CAM heroines. The
      new phylogeny of the tribe Heroini provides robust framework to stabilize the
      taxonomy of the group and for future comparative studies on these morphologically
      and ecologically diverse freshwater fishes. Morphology was mostly informative at
      the genus level and aid in determining the monophyly and composition of heroine
      genera. Upon acceptance of all putative genera, as recovered in this study, the
      Heroini would be with 35 genera the most genus-rich clade of Neotropical
      cichlids.

PMID- 18725306
TI  - Dating of divergences within the Rattus genus phylogeny using whole mitochondrial
      genomes.
AB  - The timing and order of divergences within the genus Rattus have, to date, been
      quite speculative. In order to address these important issues we sequenced six
      new whole mitochondrial genomes from wild-caught specimens from four species,
      Rattus exulans, Rattus praetor, Rattus rattus and Rattus tanezumi. The only rat
      whole mitochondrial genomes available previously were all from Rattus norvegicus
      specimens. Our phylogenetic and dating analyses place the deepest divergence
      within Rattus at approximately 3.5 million years ago (Mya). This divergence
      separates the New Guinean endemic R. praetor lineage from the Asian lineages.
      Within the Asian/Island Southeast Asian clade R. norvegicus diverged earliest at
      approximately 2.9Mya. R. exulans and the ancestor of the sister species R. rattus
      and R. tanezumi subsequently diverged at approximately 2.2Mya, with R. rattus and
      R. tanezumi separating as recently as approximately 0.4Mya. Our results give both
      a better resolved species divergence order and diversification dates within
      Rattus than previous studies.

PMID- 18725307
TI  - Phylogenetic relationships among zooxanthellae (Symbiodinium) associated to
      excavating sponges (Cliona spp.) reveal an unexpected lineage in the Caribbean.
AB  - Phylogenetic relationships of symbiotic dinoflagellate lineages, distributed in
      all tropical and subtropical seas, suggest strategies for long distance dispersal
      but at the same time strong host specialization. Zooxanthellae (Symbiodinium:
      Dinophyta), which are associated to diverse shallow-water cnidarians, also engage
      in symbioses with some sponge species of the genus Cliona. In the Caribbean,
      zooxanthellae-bearing Cliona has recently become abundant due to global warming,
      overfishing, and algae abundance. Using molecular techniques, the symbionts from
      five excavating species (Clionacaribbaea, C. tenuis, C. varians, C. aprica and C.
      laticavicola) from the southern and southwestern Caribbean were surveyed. Several
      DNA sequence regions were used in order to confirm zooxanthellae identity; 18S
      rDNA, domain V of chloroplast large subunit (cp23S), internal transcribed spacer
      2 (ITS2), and ITS2 secondary structure. Sequence analyses corroborated the
      presence of three zooxanthellae clades: A, B, and G. Presence of clades A and B
      in common boring sponges of the Caribbean fit with the general pattern of the
      province. The discovery of clade G for the first time in any organism of the
      Atlantic Ocean leads us to consider this unusual finding as a phylogenetic relict
      through common ancestors of sponge clades or an invasion of the sponge from the
      Indo-Pacific.

PMID- 18725308
TI  - Establishment and functional characterization of a tracheal epithelial cell line
      RTEC11 from transgenic rats harboring temperature-sensitive simian virus 40 large
      T-antigen.
AB  - A tracheal epithelial cell line RTEC11 was established from transgenic rats
      harboring temperature-sensitive simian virus 40 large T-antigen. The cells grew
      continuously at a permissive temperature of 33 degrees C but not at a non
      permissive temperature of 39 degrees C. Morphological and functional
      investigations demonstrated that the cells were polarized epithelial cells
      maintaining a regulated permeability barrier function. Interestingly, the
      expression levels of Muc1 (mucin 1) and Scgb1a1 (uteroglobin), non-ciliated
      secretory cell markers, and Tubb4 (tubulin beta 4), a ciliated cell marker, were
      significantly increased under the cell growth-restricted condition. Global gene
      expression and computational network analyses demonstrated a significant genetic
      network associated with cellular development and differentiation in cells
      cultured at the non-permissive temperature. The tracheal epithelial cell line
      RTEC11 with unique characteristics should be useful as an in vitro model for
      studies of the physiological functions and gene expression of tracheal epithelial
      cells.

PMID- 18725309
TI  - Adenoviral-mediated interleukin-18 expression in mesenchymal stem cells
      effectively suppresses the growth of glioma in rats.
AB  - Glioma is the most common primary intracranial malignant tumor. Despite advances
      in surgical techniques and adjuvant radio- and chemotherapies, the prognosis for
      patients with glioma remains poor. We have explored the effects of using
      genetically modified mesenchymal stem cells (MSCs) to treat malignant glioma in
      rats. Mesenchymal stem cells isolated from Sprague-Dawley rats can directly
      suppress the growth of C6 cells in vitro. MSCs transplanted intratumorally can
      also significantly inhibit the growth of glioma and prolong survival in C6 glioma
      bearing models. MSCs producing Interleukin-18 infected by adenoviral vector
      inhibited glioma growth and prolonged the survival of glioma-bearing rats.
      Transplantation of IL-18 secreting MSCs was associated with enhanced T cell
      infiltration and long-term anti-tumor immunity. Thus, IL-18 may be an effective
      adoptive immunotherapy for malignant glioma. When used in conjunction with MSCs
      as targeting vehicles in vivo, IL-18 may offer a promising new treatment option
      for malignant glioma.

PMID- 18725310
TI  - Centrosome overduplication and mitotic instability in PKD2 transgenic lines.
AB  - Polycystin-2 (PC-2), a protein encoded by PKD2 and involved in autosomal dominant
      polycystic kidney disease (ADPKD), is a non-selective cationic channel recently
      implicated in the function of primary cilia. We recently constructed a new animal
      model in the form of a transgenic mouse with a BAC-containing human PKD2 inserted
      in its genome. Two transgenic mouse lines overexpressing human PKD2 showed
      mitotic instability. Fibroblasts from these transgenic mouse lines have abnormal
      chromosomal numbers. These lines also have supernumerary centrosomes. PC-2
      overexpression is associated with mitotic instability and centrosome
      overduplication. PC-2 therefore seems to play a role in centrosome duplication,
      and this hypothesis is being evaluated in other models.

PMID- 18725311
TI  - Central administration of galanin stimulates feeding behavior in chicks.
AB  - Galanin is recognized as one of the orexigenic peptides in the brain of mammals
      and fishes. The amino acid sequence of chicken galanin and its distribution in
      the brain are similar to those of mammals, suggesting that the brain galanin
      might be related to feeding regulation in chicks. The purpose of the present
      study was to investigate whether intracerebroventricular (ICV) injection of
      galanin affected feeding behavior of chicks (Gallus gallus). The injection of
      galanin increased food intake of layer and broiler chicks. We also found that the
      galanin-induced feeding behavior was attenuated in layer chicks by the co
      injection of yohimbine and beta-funaltrexamine, which are the antagonists of
      adrenergic alpha-2 receptor and opioid mu-receptor, respectively. It is therefore
      possible that the orexigenic effect of galanin is mediated by these receptors.

PMID- 18725312
TI  - Vitellin-binding proteins in the nematode Oscheius tipulae (Nematoda,
      Rhabditida).
AB  - We describe the first application of a non-radioactive ligand-blotting technique
      to the characterization of proteins interacting with nematode vitellins.
      Chromatographically purified vitellins from the free-living nematode Oscheius
      tipulae were labeled with fluorescein in vitro. Ligand-blotting assays with
      horseradish peroxidase-conjugated anti-fluorescein antibodies showed that labeled
      vitellins reacted specifically with a polypeptide of approximately 100 kDa, which
      we named P100. This polypeptide is a specific worm's vitellin-binding protein
      that is present only in adult worms. Blots containing purified O. tipulae
      vitellin preparations showed no detectable signal in the 100 kDa region, ruling
      out any possibility of yolk polypeptides self-assembling under the conditions
      used in our assay. Experiments done in the presence of alpha-methyl mannoside
      ruled out the possibility of vitellins binding to P100 through mannose residues.
      Triton X-114 fractionation of whole worm extracts showed that P100 is either a
      membrane protein or has highly hydrophobic regions.

PMID- 18725313
TI  - Metabolic engineering of the non-sporulating, non-solventogenic Clostridium
      acetobutylicum strain M5 to produce butanol without acetone demonstrate the
      robustness of the acid-formation pathways and the importance of the electron
      balance.
AB  - The primary alcohol/aldehyde dehydrogenase (coded by the aad gene) is responsible
      for butanol formation in Clostridium acetobutylicum. We complemented the non
      sporulating, non-solvent-producing C. acetobutylicum M5 strain (which has lost
      the pSOL1 megaplasmid containing aad and the acetone-formation genes) with aad
      expressed from the phosphotransbutyrylase promoter and restored butanol
      production to wild type levels. Because no acetone was produced, no acids
      (acetate or butyrate) were re-assimilated leading to high butyrate but especially
      acetate levels. To counter acetate production, we examined thiolase
      overexpression in order reduce the acetyl-CoA pool and enhance the butyryl-CoA
      pool. We combined thiolase overexpression with aad overexpression aiming to also
      enhance butanol formation. While limiting the formation of acetate and ethanol,
      the butanol titers were not improved. We also generated acetate kinase (AK) and
      butyrate kinase (BK) knockout (KO) mutants of M5 using a modified protocol to
      increase the antibiotic-resistance gene expression. These strains exhibited
      greater than 60% reduction in acetate or butyrate formation, respectively. We
      complemented the AKKO M5 strain with aad overexpression, but could not
      successfully transform the BKKO M5 strain. The AKKO M5 strain overexpressing aad
      produced less acetate, but also less butanol compared to the M5 aad
      overexpression strain. These data suggest that loss of the pSOL1 megaplasmid
      renders cells resistant to changes in the two acid-formation pathways, and
      especially so for butyrate formation. We argue that the difficulty in generating
      high butanol producers without acetone and acid production is hindered by the
      inability to control the electron flow, which appears to be affected by unknown
      pSOL1 genes.

PMID- 18725314
TI  - Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in
      human synovial cells through a protein moiety.
AB  - Borrelia burgdorferi invasion of mammalian joints results in genesis of Lyme
      arthritis. Other than spirochete lipids, existence of protein antigens, which are
      abundant in joints and participate in B. burgdorferi-induced host inflammatory
      response, is unknown. Here, we report that major products of the B. burgdorferi
      basic membrane protein (bmp) A/B operon that are induced in murine and human
      joints, possess inflammatory properties. Compared to the wild type B.
      burgdorferi, an isogenic bmpA/B mutant induced significantly lower levels of pro
      inflammatory cytokines TNF-alpha and IL-1beta in cultured human synovial cells,
      which could be restored using bmpA/B-complemented mutants, and more directly,
      upon addition of recombinant BmpA, but not BmpB or control spirochete proteins.
      Non-lipidated and lipidated versions of BmpA induced similar levels of cytokines,
      and remained unaffected by treatment with lipopolysaccharide inhibitor, polymyxin
      B. The bmpA/B mutant was also impaired in the induction of NF-kappaB and p38 MAP
      kinase signaling pathways in synovial cells, which were activated by non
      lipidated BmpA. These results show that a protein moiety of BmpA can induce
      cytokine responses in synovial cells via activation of the NF-kappaB and p38 MAP
      kinase pathways and thus, could potentially contribute to the genesis of Lyme
      arthritis.

PMID- 18725315
TI  - Dendritic cells from C57BL/6 mice undergo activation and induce Th1-effector cell
      responses against Campylobacter jejuni.
AB  - Food-borne Campylobacter jejuni (Cj) is an important cause of enteritis. We
      showed that C57BL/6 and congenic interleukin (IL)-10(-/-) mice serve as models of
      Cj colonization and enteritis, respectively. Thus, C57BL/6 mice are resistant to
      Cj induced disease. Because dendritic cells (DCs) are central to regulating
      adaptive immune responses, we investigated the interaction of Cj with murine bone
      marrow-derived DCs (BM-DCs) to assess bacterial killing, DC activation, and the
      ability of Cj-infected BM-DCs to stimulate Campylobacter-specific T cell
      responses in vitro. BM-DCs challenged with Cj efficiently internalized and killed
      Cj 11168 and significantly upregulated surface MHC-II, CD40, CD80 and CD86
      demonstrating a mature phenotype. Infected BM-DCs secreted significant amounts of
      tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-12p70. Formalin-killed Cj
      also induced maturation of BM-DCs with similar cytokine production but at a
      significantly lower magnitude than live bacteria. Maximal activation of murine BM
      DCs required internalization of Cj; attachment alone was not sufficient to elicit
      significant responses. Also, various strains of Cj elicited different magnitudes
      of cytokine production from BM-DCs. Finally, in a coculture system, Cj-infected
      BM-DCs induced high level interferon-gamma (INF-gamma) production from CD4+T
      cells indicating Th1 polarization. Thus, DCs from resistant C57BL/6 mice initiate
      T cell responses against Cj.

PMID- 18725317
TI  - Interleukin-23: immunological roles and clinical implications.
AB  - Increasing evidence has revealed the importance of IL-23, which closely resembles
      IL-12 both structurally and immunologically, in linking innate and adaptive
      immunity. IL-23, produced by activated type 1 macrophages and dendritic cells
      (DC), possesses unique roles in the differentiation and expansion of memory T
      cells. IL-23 has been associated with several inflammatory diseases such as
      rheumatoid arthritis, inflammatory bowel disease (IBD) and Helicobacter pylori
      associated gastritis, mainly due to its capacity to induce a strong Th1 type
      immune response. IL-23 is also associated with Th17 responses and the cytokine
      produced by the antigen presenting cells (APC), i.e. IL-12 vs IL-23 determines in
      part if a response is Th1 or Th17. Recent studies have also associated chronic
      inflammatory diseases such as IBD, psoriasis and myocardial infarction with
      polymorphisms of the IL-23 receptor complex. The current review focuses on the
      immunological role of IL-23 and possible therapeutic avenues for inflammatory
      diseases.

PMID- 18725318
TI  - 24(S),25-epoxycholesterol: a messenger for cholesterol homeostasis.
AB  - The oxysterol 24(S),25-epoxycholesterol is made in a shunt in the cholesterol
      biosynthetic pathway in all cholesterogenic cells. Evidence is emerging that
      endogenous 24(S),25-epoxycholesterol can work at several levels to control acute
      cholesterol homeostasis. For instance, this oxysterol suppresses activation of
      the master regulators of cholesterol homeostasis, the sterol regulatory element
      binding proteins. Indeed, 24(S),25-epoxycholesterol appears to serve as a measure
      of cholesterol synthesis and to protect against surges in the production of this
      potentially cytotoxic molecule. In addition, endogenous 24(S),25-epoxycholesterol
      is a natural ligand for the liver X receptors which induce expression of
      cholesterol efflux-related genes. Levels of endogenous 24(S),25-epoxycholesterol
      can be artificially elevated by partially inhibiting the step after the start of
      the shunt, catalysed by oxidosqualene cyclase. The idea of manipulating a self
      governing pathway for the production of a physiological regulator, that can
      enhance cholesterol removal and decrease uptake and synthesis, is attractive and
      warrants further evaluation.

PMID- 18725319
TI  - Zn(II)-dependent histone deacetylase inhibitors: suberoylanilide hydroxamic acid
      and trichostatin A.
AB  - Suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza) and trichostatin A
      (TSA) are inhibitors of the Zn(II)-dependent class I and class II histone
      deacetylases (HDACs), which are enzymes that operate in concert with histone
      acetyltransferases (HATs) to regulate the acetylation status of the epsilon-amino
      group of lysine residues of nucleosomal histones in chromatin. An increased level
      of histone acetylation resulting from the SAHA or TSA inhibition of Zn(II)
      dependent HDACs relaxes the chromatin structure and upregulates transcription.
      The links made in the 1990s between the inhibition of HDAC activity and the
      suppression of tumor growth have brought the design of HDAC inhibitors (HDACi) to
      the forefront of oncology research. SAHA has anticancer activity against
      hematologic and solid tumors and has been approved by the FDA for the treatment
      of cutaneous T-cell lymphoma. The increased molecular-level understanding of
      class I and class IIa HDACs from X-ray crystallography highlights differences in
      the residues distal to the active site and in the cavity size, which has
      implications for HDACi substrate specificity and enzyme mechanism. Results from
      HDAC-focussed activity-based protein profiling experiments may lead to the design
      of molecules that are class-specific HDACi.

PMID- 18725320
TI  - The design, structures and therapeutic potential of protein epitope mimetics.
AB  - Using a biologically relevant peptide or protein structure as a starting point
      for lead identification represents one of the most powerful approaches in modern
      drug discovery. Here, we focus on the protein epitope mimetic (PEM) approach,
      where folded 3D structures of peptides and proteins are taken as starting points
      for the design of synthetic molecules that mimic key epitopes involved in protein
      protein and protein-nucleic acid interactions. By transferring the epitope from a
      recombinant to a synthetic scaffold that can be produced by parallel
      combinatorial methods, it is possible to optimize target affinity and specificity
      as well as other drug-like ADMET properties. The PEM technology is a powerful
      tool for target validation, and for the development of novel PEM-based drugs.

PMID- 18725316
TI  - Endocannabinoids in the retina: from marijuana to neuroprotection.
AB  - The active component of the marijuana plant Cannabis sativa, Delta9
      tetrahydrocannabinol (THC), produces numerous beneficial effects, including
      analgesia, appetite stimulation and nausea reduction, in addition to its
      psychotropic effects. THC mimics the action of endogenous fatty acid derivatives,
      referred to as endocannabinoids. The effects of THC and the endocannabinoids are
      mediated largely by metabotropic receptors that are distributed throughout the
      nervous and peripheral organ systems. There is great interest in endocannabinoids
      for their role in neuroplasticity as well as for therapeutic use in numerous
      conditions, including pain, stroke, cancer, obesity, osteoporosis, fertility,
      neurodegenerative diseases, multiple sclerosis, glaucoma and inflammatory
      diseases, among others. However, there has been relatively far less research on
      this topic in the eye and retina compared with the brain and other organ systems.
      The purpose of this review is to introduce the "cannabinergic" field to the
      retinal community. All of the fundamental works on cannabinoids have been
      performed in non-retinal preparations, necessitating extensive dependence on this
      literature for background. Happily, the retinal cannabinoid system has much in
      common with other regions of the central nervous system. For example, there is
      general agreement that cannabinoids suppress dopamine release and presynaptically
      reduce transmitter release from cones and bipolar cells. How these effects relate
      to light and dark adaptations, receptive field formation, temporal properties of
      ganglion cells or visual perception are unknown. The presence of multiple
      endocannabinoids, degradative enzymes with their bioactive metabolites, and
      receptors provides a broad spectrum of opportunities for basic research and to
      identify targets for therapeutic application to retinal diseases.

PMID- 18725321
TI  - Aflatoxin B1-induced TP53 mutational pattern in normal human cells using the
      FASAY (Functional Analysis of Separated Alleles in Yeast).
AB  - Mutations in the TP53 gene are the most common alterations in human tumours. In
      hepatocellular carcinoma (HCC) related to exposure to aflatoxin B1, a specific
      G>T transversion in codon 249 is classically described as a hot spot. However,
      AFB1 is suspected to be a potent carcinogen in tissues other than the liver. By
      using the FASAY functional assay in yeast, the present study aimed at depicting
      the mutational pattern of TP53 in normal human fibroblasts after in vitro
      exposure to AFB1. Molecular analysis of mutants revealed that codon 245 was the
      main hot spot, whereas no mutations were found in codon 249. The locations of
      mutations within GG and GC/CG sequences are well in accordance with AFB1-adduct
      location data. In our assay with normal human fibroblasts, AFB1 mainly induced
      G>A transitions, followed by G>T and A>G mutations. This suggests that G>T
      transversions at codon 249 were likely the result of a selection bias in human
      HCC rather than a true fingerprint of AFB1 adducts. Indeed, a comparison of the
      mutation pattern with that found in human HCC excluding codon 249 reveals that
      the two spectra are quite similar. Furthermore, the similarity between our in
      vitro spectrum with that identified in AFB1-induced lung tumours in mice suggests
      that AFB1 may be a potent lung carcinogen in humans.

PMID- 18725322
TI  - Influence of food ration, copper exposure and exercise on the energy metabolism
      of common carp (Cyprinus carpio).
AB  - The present study was conducted to extend the understanding of the combined
      physiological effects of different food rations in combination with sublethal
      levels of copper in common carp (Cyprinus carpio). Fish acclimated to low (0.5%
      body weight) and high (5% body weight) food rations were exposed to 1 microM
      copper for a period of 28 days and kept for a further 14 days in copper free
      water to examine their recovery. Measurements of oxygen consumption, ammonia
      excretion and ammonia accumulation in plasma and muscle were done at various time
      intervals during the experimental period. Overall, oxygen consumption and ammonia
      excretion rates were significantly affected by food ration in both copper free
      and copper exposed fish. Additional challenges, such as copper exposure and/or
      exercise, significantly increased plasma and muscle ammonia in the fish fed a
      high food ration. Muscle ammonia levels in general responded slower (first
      increase after 72 h) and recovered within 2 weeks of exposure. There was a
      significant correlation between plasma ammonia levels, muscle ammonia levels and
      ammonia excretion rates. Influence of copper in terms of ammonia excretion and
      plasma ammonia accumulation was observed in high ration fish but low ration fish
      remained unaffected. This clearly indicates that ammonia metabolism was
      significantly influenced by copper in this group of fish showing that during
      unfavourable environmental conditions a high amount of food supply may turn
      deleterious to fish.

PMID- 18725323
TI  - Heavy metals generate reactive oxygen species in terrestrial and aquatic ciliated
      protozoa.
AB  - Reactive oxygen species (ROS) induction by exposure to heavy metals (Cd, Cu or
      Zn) in diverse free-living ciliated protozoa (Tetrahymena sp. and three strains
      of Colpoda steinii, isolated from freshwater and soils with different level of
      metal pollution) has been evaluated. Using specific fluorophores, such as 2',7'
      dichlorofluorescein diacetate, hydroethidine and dihydrorhodamine 123, and a
      fluorescence microscope with the program MetaMorph Imaging System 4.0, we have
      analyzed both the average fluorescence emission and the heterogeneous
      distribution of fluorescence in control and treated cells. This is the first time
      that these fluorophores are used to detect ROS production in ciliated protozoa.
      All metals generate ROS, mainly superoxide and peroxides, showing a remarkable
      inter- and intra-specific variations. Likewise, resistance against each metal was
      also very diverse. Cu and specially Cd, the most toxic heavy metal for these
      ciliates, are the best oxidative stress inducers. However, a correlation between
      fluorescence emission intensity and cellular metal sensitivity for each strain
      cannot be established. Results are discussed and compared with similar findings
      previously published in other unicellular and pluricellular organisms.

PMID- 18725324
TI  - Wogonin inhibits microglial cell migration via suppression of nuclear factor
      kappa B activity.
AB  - Previously, we and others have demonstrated that wogonin, an active component
      from the root of Scutellaria baicalensis Georgi, has a neuroprotective effect in
      cerebral ischemic insult. The neuroprotective effect of wogonin may at least in
      part be due to its anti-inflammatory properties. Microglial cells, well-known
      residential macrophages in the central nervous system, migrate to the ischemic
      lesion and play a pivotal role in the development of chronic inflammation. In the
      present study, we observed that wogonin potently inhibited microglial migration
      toward a chemokine, monocyte chemoattractant protein-1 (MCP-1). The anti
      migratory effect of wogonin was provoked at nanomolar concentrations, at which
      wogonin did not significantly inhibit the production of cytokines and chemokines.
      NF-kappaB has previously shown to regulate microglial cell migration, and
      activation of cAMP-signaling pathway has also been associated with inhibition of
      microglial cell motility. In the present study, wogonin at low micromolar
      concentrations completely suppressed the activity of NF-kappaB in MCP-1
      stimulated microglia, and NF-kappaB inhibitors such as N-acetyl cysteine and
      pyrrolidinedithiocarbamate inhibited the MCP-1-induced migration of microglial
      cells. However, wogonin did not stimulate the production of cAMP in microglial
      cells. Our results indicate that the anti-inflammatory activity of wogonin is
      exerted at least in part by suppressing microglial cell motility via inhibition
      of NF-kappaB activity.

PMID- 18725325
TI  - Exploring the complex relationships between infections and autoimmunity.

PMID- 18725326
TI  - Therapeutic potential of CD8+ cytotoxic T lymphocytes in SLE.
AB  - Recent evidence supports the idea that following a break in tolerance, CD8
      cytotoxic T lymphocytes (CTL) may be an important but unrecognized mechanism for
      limiting expansion of autoreactive B cells. Failure of this mechanism could allow
      persistence of CD4 T cell driven polyclonal B cell activation resulting in
      clinical lupus. Although CD8 CTL failure may occur early in disease, work in mice
      supports the concept that therapeutic CTL enhancement may be both practical and
      beneficial in lupus. Devising such therapy for humans will first require an
      understanding of the in vivo mechanisms critical in CTL expansion and down
      regulation, particularly in the lupus setting which may differ from CTL
      generation in other clinical settings (e.g. tumors, infections).

PMID- 18725327
TI  - Chronic fatigue syndrome with autoantibodies--the result of an augmented adjuvant
      effect of hepatitis-B vaccine and silicone implant.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) that defines by prolonged fatigue and
      other manifestations, was recently integrated into a spectrum of central
      sensitivity syndromes including several diseases as fibromylagia. CFS etiology is
      multi-factorial commonly triggered by infectious agents. Vaccines, induce an
      immune response similarly to infections, and may trigger just like infections
      autoimmune diseases, CFS and fibromyalgia. Furthermore vaccines contain an
      adjuvant which enhances their immune stimulation. CASE PRESENTATION: A 56-year
      old woman was diagnosed with CFS accompanied by fibromyalgia, demyelination and
      autoantibodies. Her illness begun following the 2nd dose of hepatitis-B vaccine,
      and was aggravated by the 3rd vaccination. She underwent silicone breast
      implantation 6 years before vaccination with no adverse events. However, between
      the 2nd and 3rd vaccination she suffered a breast injury with local inflammation.
      Upon explanation of her breast implants silicone leak was observed. DISCUSSION:
      Vaccines have been reported to precede CFS mainly following exposure to multiple
      vaccinations (e.g. the Gulf war syndrome), or as an adverse response to the
      vaccine adjuvant (e.g. the macrophagic myofasciitis syndrome). Silicone is
      considered an adjuvant to the immune system, and may induce "the adjuvant
      disease". Silicone implant, especially silicone leak relationship with
      autoimmunity and CFS has been the focus of considerable debates. CONCLUSION: Our
      patient illness started following hepatitis-B vaccine, suggesting that it was
      caused or accelerated by vaccination. In parallel to vaccination our patient
      suffered from breast injury, which might represent the time of silicone leak. The
      exposure to the adjuvant, silicone, might have augmented her immune response to
      the vaccine. To the best of our knowledge this is the first case of combined
      adverse effect to vaccine and silicone. Vaccine safety in individuals with
      silicone implants requires further studies.

PMID- 18725328
TI  - Nucleotide-dependent self-assembly of Nucleoside Diphosphate Kinase (NDPK) in
      vitro.
AB  - In addition to their role in nucleotide homeostasis, members of the Nucleoside
      Diphosphate Kinase (NDPK) family have been implicated in tumor metastasis, cell
      migration and vesicle trafficking. Although its role in most cases depends on
      nucleotide catalysis, a precise understanding of how the catalytic activity of
      NDPK supports its function in diverse processes is lacking. Here we report that
      wild type, but not catalytically inactive (H118C) NDPKB, undergoes dynamic self
      assembly into ordered 20-25 nm diameter filaments in vitro. Self-assembly is
      nucleoside triphosphate dependent, GTP being most effective at promoting polymer
      formation. In addition, polymerization appears to depend on formation of the
      phosphoryl-Histidine intermediate of the enzyme, suggesting a previously
      unappreciated conformational change in NDPK during its catalytic cycle. We
      hypothesize that the observed nucleotide-dependent self-assembly property of
      NDPKB may reflect a key feature of NDPK enzymes that enables their function in
      diverse processes.

PMID- 18725329
TI  - Role of residues in the adenosine binding site of NAD of the Ascaris suum malic
      enzyme.
AB  - Ascaris suum mitochondrial malic enzyme catalyzes the divalent metal ion
      dependent conversion of l-malate to pyruvate and CO(2), with concomitant
      reduction of NAD(P) to NAD(P)H. In this study, some of the residues that form the
      adenosine binding site of NAD were mutated to determine their role in binding of
      the cofactor and/or catalysis. D361, which is completely conserved among species,
      is located in the dinucleotide-binding Rossmann fold and makes a salt bridge with
      R370, which is also highly conserved. D361 was mutated to E, A and N. R370 was
      mutated to K and A. D361E and A mutant enzymes were inactive, likely a result of
      the increase in the volume in the case of the D361E mutant enzyme that caused
      clashes with the surrounding residues, and loss of the ionic interaction between
      D361 and R370, for D361A. Although the K(m) for the substrates and isotope effect
      values did not show significant changes for the D361N mutant enzyme, V/E(t)
      decreased by 1400-fold. Data suggested the nonproductive binding of the cofactor,
      giving a low fraction of active enzyme. The R370K mutant enzyme did not show any
      significant changes in the kinetic parameters, while the R370A mutant enzyme gave
      a slight change in V/E(t), contrary to expectations. Overall, results suggest
      that the salt bridge between D361 and R370 is important for maintaining the
      productive conformation of the NAD binding site. Mutation of residues involved
      leads to nonproductive binding of NAD. The interaction stabilizes one of the
      Rossmann fold loops that NAD binds. Mutation of H377 to lysine, which is
      conserved in NADP-specific malic enzymes and proposed to be a cofactor
      specificity determinant, did not cause a shift in cofactor specificity of the
      Ascaris malic enzyme from NAD to NADP. However, it is confirmed that this residue
      is an important second layer residue that affects the packing of the first layer
      residues that directly interact with the cofactor.

PMID- 18725330
TI  - Non-native glyceraldehyde-3-phosphate dehydrogenase can be an intrinsic component
      of amyloid structures.
AB  - Interactions between different forms of glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) and amyloid-beta peptide (1-42) were investigated by direct (surface
      plasmon resonance) and indirect (kinetics of spontaneous and GroEL/S-assisted
      reactivation of denatured GAPDH) methods. It was demonstrated that non-native
      forms of GAPDH obtained by different ways (cold denaturation, oxidation of the
      enzyme, and its unfolding in guanidine hydrochloride) efficiently bind to soluble
      amyloid-beta peptide (1-42) yielding a stable complex. Native tetrameric GAPDH
      does not interact with soluble amyloid-beta peptide (1-42), neither non-native
      forms of GAPDH interact with aggregated amyloid-beta peptide (1-42). The results
      suggest that non-native GAPDH species can be involved in the formation of amyloid
      structures during Alzheimer's disease, binding to soluble amyloid-beta peptide (1
      42).

PMID- 18725331
TI  - Simultaneous refolding and purification of a recombinant lipase with an intein
      tag by affinity precipitation with chitosan.
AB  - A strategy for simultaneous purification and refolding of proteins overexpressed
      with an intein tag is described. A recombinant lipase overexpressed in
      Escherichia coli ER2566 with the intein tag and obtained as inclusion bodies was
      solubilized in buffer containing 8 M urea or cetyltrimethylammonium bromide. The
      solubilized lipase was precipitated with chitosan and the affinity complex of the
      polymer with the fusion protein was obtained. The intein tag was cleaved with
      dithiothreitol and the refolded lipase was obtained in active form. Activity
      recovery of 80% was observed and the enzyme had a specific activity of 2965
      units/mg. The purified lipase showed a single band on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The purity and activity recovery were
      comparable with that of the preparation obtained by using the commercial kit
      which utilizes chromatography on chitin beads. The purified and refolded lipase
      was characterized by fluorescence and CD spectroscopy.

PMID- 18725332
TI  - 1.4Mb recurrent 22q11.2 distal deletion syndrome, two new cases expand the
      phenotype.
AB  - We report two new patients with the 1.4Mb recurrent 22q11.2 distal deletion
      syndrome. Features common to both children, as well as to several of the
      previously reported cases, include normal palate, smooth philtrum, hypoplastic
      alae nasi and delayed development. Both children are small but not growth
      retarded, and are microcephalic. Their developmental delay is global and most
      pronounced for language acquisition. One child has unilateral sensorineural
      hearing loss and encopresis, and the other child has treatment-responsive
      nocturnal epileptogenic activity. These two new cases confirm the recurrent
      nature of the deletion and help to further delineate the phenotype.

PMID- 18725334
TI  - Molecular basis for affected cartilage formation and bone union in fracture
      healing of the streptozotocin-induced diabetic rat.
AB  - Most studies have focused on the association between diabetes mellitus (DM) and
      impaired osseous healing, but there is also evidence that diabetes impairs
      cartilage formation during fracture healing. To investigate the molecular
      mechanisms by which diabetes affects endochondral ossification, experiments were
      performed in a model of rat closed fracture healing complicated with diabetes.
      Diabetic rats were created by a single intravenous injection of streptozotocin
      (STZ), while controls were treated with vehicle alone. Fractures were made 2
      weeks after STZ injection. Animals were killed at 4, 7, 10, 14, 21, 28 and 42
      days following fracture, and samples were subject to radiographic, histological
      and molecular analyses. In the DM group, a significantly smaller cartilaginous
      callus was formed compared with controls throughout healing, with the cartilage
      area being reduced rapidly after day 14. When the bone union rate was evaluated
      radiographically on day 28, DM calluses exhibited a lower rate than controls.
      However, when evaluated on day 42, both groups showed an equivalent union rate.
      Cellular proliferation of chondroprogenitor cells and proliferating chondrocytes
      in soft calluses of the DM group was significantly reduced during early stages of
      healing (days 4 and 7), but no longer reduced thereafter. Moreover, expression
      levels of collagen type II, type X and osteopontin (OPN) were constantly low in
      the DM group. These results show the molecular basis for diminished cartilage
      formation and delayed union in fracture healing of the STZ-induced diabetic rats.

PMID- 18725333
TI  - An insight into the salivary transcriptome and proteome of the soft tick and
      vector of epizootic bovine abortion, Ornithodoros coriaceus.
AB  - The salivary glands of blood-sucking arthropods contain a redundant 'magic
      potion' that counteracts their vertebrate host's hemostasis, inflammation, and
      immunity. We here describe the salivary transcriptome and proteomics (sialome) of
      the soft tick Ornithodoros coriaceus. The resulting analysis helps to consolidate
      the classification of common proteins found in both soft and hard ticks, such as
      the lipocalins, Kunitz, cystatin, basic tail, hebraein, defensin, TIL domain,
      metalloprotease, 5'-nucleotidase/apyrase, and phospholipase families, and also to
      identify protein families uniquely found in the Argasidae, such as the
      adrenomedullin/CGRP peptides, 7DB, 7 kDa, and the RGD-containing single-Kunitz
      proteins. Additionally, we found a protein belonging to the cytotoxin protein
      family that has so far only been identified in hard ticks. Three other unique
      families common only to the Ornithodoros genus were discovered. Edman
      degradation, 2D and 1D-PAGE of salivary gland homogenates followed by tryptic
      digestion and HPLC MS/MS of results confirms the presence of several proteins.
      These results indicate that each genus of hematophagous arthropods studied to
      date evolved unique protein families that assist blood feeding, thus
      characterizing potentially new pharmacologically active components or
      antimicrobial agents.

PMID- 18725335
TI  - A longitudinal study of the relationship of physical activity to bone mineral
      accrual from adolescence to young adulthood.
AB  - Physical activity in adolescence is beneficial for increasing bone mineral
      accrual; however, it's unclear whether these benefits persist into adulthood.
      This prospective study investigated whether physically active adolescents
      maintained their higher bone mineral content (BMC) into the third decade of life
      when compared to their less active peers. Data were from 154 subjects (82 females
      and 72 males) who participated in the University of Saskatchewan's Pediatric Bone
      Mineral Accrual Study (1991-1997), entry age 8 to 15 years. Participants returned
      for follow-up as young adults (2002-2006), follow-up age 23 to 30 years. Dual
      energy X-ray absorptiometry was used to measure BMC of total body (TB), lumbar
      spine (LS), total hip (TH) and femoral neck (FN) annually from 1991 to 1997 and
      from 2002 to 2006. Peak height velocity (PHV) was determined for each child as a
      measure of maturity. Age and gender-specific activity Z-scores were calculated
      for each participant based on the mean physical activity scores obtained from bi
      annual questionnaire data during childhood and adolescence. Subjects were ranked
      into three adolescent activity groups: active, average and inactive (top, middle
      two, and bottom quartiles, respectively). Analysis of covariance (ANCOVA) was
      used to compare adjusted TB, LS, TH and FN BMC across the three adolescent
      activity groups at 1 year post PHV and in young adulthood. When compared to the
      inactive group, active males had 8% greater adjusted BMC at the TB, 13% at the LS
      and 11% at the TH (p<0.05) in adolescence. Active females also had 8% and 15%
      more adjusted BMC (p<0.05) at the TB and LS, respectively, during adolescence. In
      young adulthood the male and female adolescent active groups were still
      significantly more active than their peers (p>0.05). It was found that active
      adolescent males had 8-10% more adjusted BMC at the TB, TH and FN (p<0.05) in
      young adulthood and that active adolescent females had 9% and 10% more adjusted
      BMC at the TH and FN. These results suggest that the skeletal benefits of
      physically activity in adolescents are maintained into young adulthood.

PMID- 18725336
TI  - [Review: delta-storage pool disease].
AB  - Platelet storage pool disease is a qualitative platelet disorder associated with
      variable degrees of reduction in the numbers and contents of dense granules
      (delta-granules). Electron microscopy is the major tool for biological diagnosis.
      Patients presenting with this platelet disorder generally show a mild bleeding
      syndrome.

PMID- 18725337
TI  - [Prognosis of chronic lymphocytic leukemia: focus on recent biomarkers].
AB  - Early stages of chronic lymphocytic leukemia (CLL), which are the most frequent
      at diagnosis, have an extremely variable individual prognosis, as some patients
      remain stable for years whereas others develop aggressive forms of the disease
      less or more rapidly. Individual prognosis evaluation of early stages of CLL is
      then a challenge for physicians; also clinico-hematological stages are still the
      evaluation basis, numerous biological markers are helpful in providing
      independent information on patient prognosis. It is useful to distinguish the
      classical prognosis factors, described in the 1980s, and the recent markers
      described from the end of the 1990s, which are widely validated for certain,
      whereas for others further investigations are needed to confirm their prognostic
      impact. We propose to detail in this review these new prognostic factors of CLL,
      especially the different serum markers, cytogenetical abnormalities of pathologic
      lymphocytes, mutational status of the immunoglobulin genes (IgVH) and CD38 and
      ZAP-70 expression.

PMID- 18725338
TI  - [Alpha 1 antitrypsin polymorphism associated to asthma and emphysema in a central
      Tunisian population].
AB  - INTRODUCTION: more than 100 alleles have been described on the alpha 1
      antitrypsin gene. Normal variants (PiM1, PiM2 and PiM3) encodes AAT molecules
      which are different but functional and normally secreted. The more frequent risk
      variants are PiS and PiZ. In this study, an AAT polymorphism analysis in
      correlation with pulmonary diseases was conducted. MATERIAL AND METHODS: analyses
      were performed on 96 asthmatics, 67 emphysema cases and 318 control subjects.
      Alpha 1 antitrypsin phenotypes were studied by quantitative determination of AAT
      concentration and isoelectrofocusing. Genotyping was performed by RFLP PCR.
      RESULTS: PiM1, PiM2, PiM3, PiS and PiZ allelic frequencies were calculated
      (0.7395, 0.2291, 0.0156, 0.0104, 0.0052 in asthmatics; 0.7547, 0.1716, 0.0298,
      0.0298, 0.0149 in emphysema patients and 0.8030, 0.1525, 0.0408, 0.006, 0.0000 in
      controls, respectively). Results showed an increase in PiM2 allele frequencies in
      both patients' groups compared to controls. Allelic frequencies difference is
      significant only with the asthmatic group (p=0,0179). PiS and PiZ deficiency
      alleles are more prevalent in the emphysema (0.0298, 0.0149) than in the
      asthmatic subjects (0.0104, 0.0052). Meanwhile, no significant difference in PiS
      and PiZ allelic frequencies was observed between patients and controls.
      CONCLUSION: PiM2 allele can be considered as genetic risk factor for asthma. PiS
      and PiZ alleles are very rare in Tunisia in comparison with the European
      population, leading to a very small contribution in pulmonary diseases
      pathogenesis in Tunisia.

PMID- 18725339
TI  - [Routine use of serial plasmatic CA 15-3 determinations during the follow-up of
      patients treated for breast cancer. Evaluation as factor of early diagnosis of
      recurrence].
AB  - PURPOSE: at our institution, CA 15-3 assays are routinely used for the early
      diagnosis of recurrence during the follow-up of patients treated for breast
      cancer, although published guidelines do not recommend this procedure. So, we
      decided to totally re-assess the usefulness of this policy. PATIENTS AND METHODS:
      all records of patients presenting a first recurrence, local (50 cases) or
      metastatic (88 cases), of breast cancer during 2003 were re-examined. An increase
      in CA 15-3 concentration of more than 25% was considered significant. RESULTS: an
      increase was observed in 18% of non metastatic recurrences. These increases had a
      prognostic value. CA 15-3 levels remained stable in 23% of metastasis cases and
      increased in 77%. In 14% of cases, the increase in CA 15-3 levels confirmed a
      clinically or radiologically suspected metastasis. Moreover, increased CA 15-3
      levels in the absence of suggestive clinical or radiological signs led to the
      diagnosis in 18% of metastasis, 50% of which involved the bone. CONCLUSION: our
      study demonstrates that CA 15-3 is useful for the early diagnosis of recurrence.
      Eighteen per cent of metastases were diagnosed by a marker increase alone. CA 15
      3 assays could be useful in the early management of these metastases in patients
      treated for breast cancer.

PMID- 18725340
TI  - [Urinary ammonium: validation of an enzymatic method and reliability with an
      indirect urine ammonium estimation].
AB  - Urinary ammonium excretion is the best parameter to quantify net acid excretion
      by the kidney. As measurement of ammonium excretion is not routinely available,
      clinicians use formulas to estimate NH(4)+ excretion. However, the measurement of
      urinary NH(4)+ concentration can be performed by an automatically method, which
      is suitable for clinical practice. The aim of this study is to evaluate the
      validity of the enzymatic method of ammonium determination with Ammonia SL
      Elitech Diagnostics reagent on an Olympus AU 2700 analyzer, which use 1/100
      diluted urine samples. A clinico-biological study allowed us to compare
      measurements obtained during a 30 months' period with the above enzymatic method
      with results obtained by a formula of calculation. Variations coefficients (CV%)
      of repeatability were less than 2.4% and, those of reproducibility tests less
      than 2,6%. Linearity was verified from 0.62 mmol/L to 158 mmol/L. Analytical
      sensitivity was 0.52 mmol/L and the correlation obtained with the assay used to
      date in the laboratory was excellent (y = 1.11 x - 1.72 ; r = 0.98). There is a
      significant positive correlation between measured concentrations obtained with
      this enzymatic method and urinary ammonium concentration estimates using the
      modified urine osmolal gap in two groups of patients, with and without mild
      chronic renal failure. As urine ammonium estimation is not reliable for detecting
      small changes in ammonium excretion, it must be absolutely measured when renal
      functional tests are performed. The assay described in this paper is simple,
      automatic and offers for the clinician accurate matter for the measurement of
      NH(4)+ excretion.

PMID- 18725341
TI  - [A novel fixed paraffin-embedded tissue processing for proteomic analysis].
AB  - Human tissues are an important biological material for the discovery of
      biomarkers and identification of novel therapeutic targets. Formalin fixed and
      paraffin embedded (FFPE) tissue represents the most abundant supply of archival
      material for clinical and molecular analyses. Although FFPE preserves the
      cellular and architectural morphologic details in tissue sections, formalin
      facilitates the formation of protein-protein crosslinks rendering FFPE tissues
      refractory to many protein studies. The aim of this study was to assess the
      feasibility of proteomic investigations of a new non-toxic fixative using a
      comprehensive panel of proteomic methods. Tissues were processed for quality and
      quantity of protein conservation, as compared to frozen and FFPE tissues using
      complementary proteomic analysis approaches. Similar protein patterns were
      observed between our tissue fixative protocol and frozen tissues using mono and
      bidimensional electrophoresis and protein identification by mass spectrometry was
      not affected. Several proteins were successfully detected using western blot and
      immunohistochemistry showed comparable results between both tissue storage
      methods. We demonstrate that our new fixative protocol represents an easy-to-use
      alternative to FFPE compatible with both current diagnostic pathology practice
      and tissue proteomic investigations.

PMID- 18725342
TI  - [Decentralization of the immunological monitoring of people living with HIV/AIDS
      in a limiting setting with a low HIV seroprevalence: the experience of Senegal].
AB  - Our work aimed to propose a manual method of counting CD4 T lymphocytes which is
      an alternative magnetic immunoseparation followed by a reading with a
      fluorescence microscope as an alternative to the automated flow cytometry. This
      alternative technique is easier for use, less expensive and could answer the
      difficulties encountered for the monitoring CD4 T cells count in developing
      countries. The specific objectives were: 1) to train the technicians of the
      peripheral sites in order to make the numeration of the CD4 T lymphocytes more
      accessible at the peripheral level; 2) to equip the sites with necessary
      facilities for the T lymphocytes CD4 count; 3) to put in place a system of
      quality control permitting the reliability of the results. A hundred and fifty
      patients have been enrolled in three care services for people living with
      HIV/AIDS in Dakar. This population was constituted of 119 seropositive and 31
      seronegative patients acting as control group to have some patients with high
      rates of T lymphocytes CD4. For the follow-up at peripheral level, the patients
      were constituted of the active line of the patients living with HIV/AIDS
      supported in the targeted sites. The measurements allowed studying concordances
      for different rates of lymphocytes: 0 to 199, 200 to 499 and over 500 cells by
      mm3. The results showed also a very good correlation (r = 0.97 or r = 0.98
      according to the operator) between the two methods for CD4 rates inferior to 500
      cells by mm3 among both the negative group and the HIV positive patients. We also
      discussed the profit of decentralization for the program and the patient, as well
      as the setting up of an external quality control to validate the alternative
      technique. According to the results, the Dynabeads is well correlated with the
      Facscount. It is a technique that can be used as an alternative in the zones with
      limited resources, low prevalence and for a small number of samples.

PMID- 18725343
TI  - [A new automated haematology analyser: the Excell 2280].
AB  - Excell 2280 analyser is a new automated haematology analyser manufactured by Drew
      Scientific Inc, Texas, USA, and distributed in France by MAXMAT S.A.,
      Montpellier. It can achieve 80 complete blood cell counts per hour, with
      leukocyte differential counts. Three sampling possibilities are included: a
      direct one (open tubes, 180 microL), a blood saver one (80 microL) and an
      automatic, through-the-cap one (180 microL). The analytic principles are:
      electrical impedance for cell counting (WBC, RBC, platelets, MCV) and
      RBC/platelet sizing; and a new multidimensional optical system using a laser
      light scattering flow cytometer for WBC counting and classification. We evaluated
      the Excell 2280 in our laboratory: we quantified intra-run and within-run
      variations, correlations between the automatic and the direct sampling method,
      stability of the results over time, linearity of the detections and finally
      correlation between results obtained with this analyzer and the Gen'S one from
      Beckman-Coulter Inc. The obtained results were within the theoretical ranges
      given by the manufacturer. The presence of any abnormal result, or of any flag,
      must systematically lead to check the blood smear. This new automated haematology
      analyser appears to be convenient for emergency room-related laboratories, and
      for routine small-to-medium laboratories.

PMID- 18725344
TI  - [Clinical value of the blood measurement of the free light chains of
      immunoglobulins].
AB  - Monoclonal free light chains are found in the serum and urine of patients with B
      cell proliferative disorders, including multiple myeloma. Measuring free light
      chains in serum is useful for the diagnosis and monitoring of free light chains
      diseases. Moreover it could be interesting in the monitoring of treated multiple
      myeloma with complete immunoglobulin and of monoclonal gammapathy of undetermined
      significance (MGUS). The goal of our work was to analyze a large cohort of
      patients with multiple myeloma or MGUS from January 2003 to August 2006 in order
      to better understand the interest of free light chains.

PMID- 18725345
TI  - [Enterovirus-related pericarditis and mediastinitis after heart surgery: a case
      report].
AB  - We report a case of enterovirus related pericarditis associated to mediastinitis
      in a hospitalised 53-year-old male after heart surgery. Mediastinitis caused by
      enterovirus has not previously been described.

PMID- 18725346
TI  - [Multiple osteonecroses and venous thrombosis: one case of patient with a novel
      mutation of protein C (N102S) and heterozygous for FV Leiden].
AB  - The association of a thrombo-embolic venous disease and multiple osteonecroses
      occurring in the presence of biological risk factors for thrombosis is rarely
      described in the literature. We report here the case of a 35-year old patient
      with such clinical manifestations. This patient is heterozygous for a novel
      mutation of the protein C gene (N102S) and for FV Leiden polymorphism. The
      clinical history is characterized by numerous thrombo-embolic venous episodes
      associated with several episodes of epiphysis osteonecrosis requiring two hip
      total prostheses and two knee total prostheses. The particular clinical features
      here are the multiple osteonecroses and the unusual localisation of brain and
      genital thromboses. The absence of both venous thromboembolic and osteonecrosis
      events in the relatives presenting the same genetic pattern suggests broad
      phenotype variations in the clinical expression of these genetic abnormalities.
      In osteonecrosis associated with thrombophilia, some authors have proposed
      treatment with stanazolol, which increase circulating protein C concentration.
      The effectiveness of this drug among such patients should be evaluated by
      clinical studies.

PMID- 18725347
TI  - [Discrepancy between two methods of D-dimers measurement: one case of human anti
      mouse antibody interference].
AB  - Quantification of D-dimers is the major biometry step in the diagnostic of an
      episode of the venous thromboembolic disease. The measurement of D-dimers can be
      performed with ELISA or immunoturbidimetric methods suited to emergency, using a
      mouse monoclonal antibody as capture and/or revelation antibody. Therefore, the
      presence in patient's plasma of human antibody mouse (HAMA) that binds the mouse
      antiglobulin used in immunoassays can lead to false negative or false positive
      results. In a young woman presenting repetitive thoracic pain suggestive of a
      pulmonary embolism, a major discrepancy was found between one result of D-dimers
      above the cut-off with an immunoturbidimetric method (STA Liatest D-DI;
      Diagnostica Stago) and one result below the cut-off with a sandwich method (Vidas
      D-Dimer Exclusion; bioMerieux). HAMA, which is known to be responsible for this
      type of discrepancy, was detected in the patient serum. The false positive result
      probably impaired with the management of patient. Taking in charge the patient
      should take into account the possible presence of this antibody. Interference by
      heterophilic antibodies is not easily detected by the laboratory. Even if their
      frequency is low, it remains a difficult problem for the biologist. Suspicion
      generally arises from inconsistency between the clinical data and immunoassay
      results. A good communication between physician and biologist should avoid to
      providing false negative or positive results.

PMID- 18725348
TI  - [Peripheral blood Sezary cells and the diagnosis of Sezary syndrome].
AB  - Sezary syndrome (SS) is a rare and aggressive cutaneous lymphoma, and its
      diagnosis is based both on clinical, histological and biological features. None
      of these criteria taken alone is specific, and the two clinical observations
      reported here agree with this. Peripheral blood involvement, due to the presence
      of a variable number of Sezary cells, has been recently fully delineated by the
      ISCL/EORTC international organizations, and taken into account in the diagnosis
      and the prognosis of this syndrome. Identification and quantification of
      peripheral blood Sezary cells on the blood smear is an essential criterion for
      the diagnosis and is sufficient when associated with relevant clinical or/and
      histological grounds. Flow cytometry is another tool to demonstrate Sezary cells
      within the peripheral blood mononuclear cells. The authors discuss about the
      respective advantages and limits of morphology and flow cytometry in the
      identification and enumeration of circulating Sezary cells. Molecular biology is
      helpful in peculiar situations.

PMID- 18725349
TI  - [Pediatric osteoarticular infections caused by Kingella kingae from 1995 to 2006
      at CHRU de Tours].
AB  - Use of molecular biology shows that Kingella kingae is a pathogen frequently
      involved in osteoarticular infections in young children. This study describes the
      cases of osteoarticular infections due to K. kingae which happened from 1995 to
      2006 in the CHRU of Tours. The description is based on clinical and biological
      features. A K. kingae specific polymerase chain reaction was performed in our
      laboratory in order to improve K. kingae osteoarticular infections diagnosis, and
      is detailed here.

PMID- 18725350
TI  - [Interference of labile glycated hemoglobin on HbA(1c) assay by a high pressure
      liquid chromatography method].
AB  - HbA(1c) assay by high pressure liquid chromatography remains submitted to
      interferences, among which that of labile HbA(1c) in 1 to 2% of samples. We have
      evaluated the interference of labile HbA(1c) on HbA(1c) assay using Variant II
      analyzer (Biorad), by in vitro formation of labile glycated haemoglobin and by
      evaluation of two protocols of elimination of labile HbA(1c) (wash and incubation
      of red blood cells in saline solution, or incubation in the wash/dilution
      solution of the analyzer). Levels of labile HbA(1c) higher than 4.5 % lead to
      underestimation of HbA(1c). The different protocols tested proved efficient and
      were adapted to routine conditions. The fastest method is the incubation of red
      blood cells in the wash/dilution solution for at least two hours, or more if
      labile fraction is unusually high.

PMID- 18725351
TI  - [A monoclonal immunoglobulin M not visible on the profile of serum capillary
      electrophoresis].
AB  - We report a case of an invisible monoclonal IgM on the profile of the serum
      electrophoresis carried out by the Paragon CZE 2000 system. This case is about a
      84 years old man followed for a Waldenstrom disease. The level of the monoclonal
      IgM given at the time of the preceding visit one year before was 10 g/L. The
      electrophoresis is reproduced in two other laboratories using respectively the
      Hydrasys and Capillarys techniques which have both shown the presence of the
      monoclonal peak. At this occasion the frequency of these anomalies of migration
      and the recommendations to avoid the erroneous interpretation of the
      electrophoresis are discussed. The vigilance and the competence of the biologist
      are essential to avoid this rare pitfall, induced by the new principle of the
      capillary electrophoresis.

PMID- 18725352
TI  - [A case of hypernatremic dehydration due to breast-feeding].
AB  - The authors report an 11-day-old exclusively breast-fed female, with a birth
      weight of 3 300 g, who had suffered from dehydration stage I, with acute renal
      failure and metabolic acidosis, with 170 mmol/L of serum sodium. Renal
      ultrasounds were normal but the rate of sodium in mother's milk was three times
      higher than controls (87 versus 21 mmol/L). Intravenous rehydration allowed the
      correction of hydroelectrolytic disorders.

PMID- 18725353
TI  - [PPAR alpha-L162V, frequency and relationship with type 2 diabetes among black
      Senegalese people].
AB  - PPARs are supposed to be involved in pathogenesis of diabetes and its
      complications. According to some authors, L162V PPARalpha gene polymorphism would
      be associated to dyslipidemia susceptibility during diabetes, whereas for some
      authors, it rather would confer resistance to these metabolic abnormalities. The
      aim of this study is to search the relationship between this polymorphism and the
      occurrence of diabetes and its complications within a Senegalese black population
      constituted of 261 diabetic and 128 controls, by comparing alleles frequencies.
      Genomic analysis for alleles identification has been performed by the allelic
      discrimination technic TaqMan 5' Nuclease, after DNA extraction (Nucleon Bacc2.
      Amersham Int.). The results of genetic variants analysis revealed that L162V
      PPARalpha polymorphism would not be present among Senegalese black population,
      and consequently, should not be involved in diabetes onset.

PMID- 18725354
TI  - Medicine 2.0: social networking, collaboration, participation, apomediation, and
      openness.
AB  - In a very significant development for eHealth, broad adoption of Web 2.0
      technologies and approaches coincides with the more recent emergence of Personal
      Health Application Platforms and Personally Controlled Health Records such as
      Google Health, Microsoft HealthVault, and Dossia. "Medicine 2.0" applications,
      services and tools are defined as Web-based services for health care consumers,
      caregivers, patients, health professionals, and biomedical researchers, that use
      Web 2.0 technologies and/or semantic web and virtual reality approaches to enable
      and facilitate specifically 1) social networking, 2) participation, 3)
      apomediation, 4) openness and 5) collaboration, within and between these user
      groups. The Journal of Medical Internet Research (JMIR) publishes a Medicine 2.0
      theme issue and sponsors a conference on "How Social Networking and Web 2.0
      changes Health, Health Care, Medicine and Biomedical Research", to stimulate and
      encourage research in these five areas.

PMID- 18725355
TI  - SOMWeb: a semantic web-based system for supporting collaboration of distributed
      medical communities of practice.
AB  - BACKGROUND: Information technology (IT) support for remote collaboration of
      geographically distributed communities of practice (CoP) in health care must deal
      with a number of sociotechnical aspects of communication within the community. In
      the mid-1990s, participants of the Swedish Oral Medicine Network (SOMNet) began
      discussing patient cases in telephone conferences. The cases were distributed
      prior to the conferences using PowerPoint and email. For the technical support of
      online CoP, Semantic Web technologies can potentially fulfill needs of knowledge
      reuse, data exchange, and reasoning based on ontologies. However, more research
      is needed on the use of Semantic Web technologies in practice. OBJECTIVES: The
      objectives of this research were to (1) study the communication of distributed
      health care professionals in oral medicine; (2) apply Semantic Web technologies
      to describe community data and oral medicine knowledge; (3) develop an online
      CoP, Swedish Oral Medicine Web (SOMWeb), centered on user-contributed case
      descriptions and meetings; and (4) evaluate SOMWeb and study how work practices
      change with IT support. METHODS: Based on Java, and using the Web Ontology
      Language and Resource Description Framework for handling community data and oral
      medicine knowledge, SOMWeb was developed using a user-centered and iterative
      approach. For studying the work practices and evaluating the system, a mixed
      method approach of interviews, observations, and a questionnaire was used.
      RESULTS: By May 2008, there were 90 registered users of SOMWeb, 93 cases had been
      added, and 18 meetings had utilized the system. The introduction of SOMWeb has
      improved the structure of meetings and their discussions, and a tenfold increase
      in the number of participants has been observed. Users submit cases to seek
      advice on diagnosis or treatment, to show an unusual case, or to create
      discussion. Identified barriers to submitting cases are lack of time, concern
      about whether the case is interesting enough, and showing gaps in one's own
      knowledge. Three levels of member participation are discernable: a core group
      that contributes most cases and most meeting feedback; an active group that
      participates often but only sometimes contribute cases and feedback; and a large
      peripheral group that seldom or never contribute cases or feedback. CONCLUSIONS:
      SOMWeb is beneficial for individual clinicians as well as for the SOMNet
      community. The system provides an opportunity for its members to share both high
      quality clinical practice knowledge and external evidence related to complex oral
      medicine cases. The foundation in Semantic Web technologies enables formalization
      and structuring of case data that can be used for further reasoning and research.
      Main success factors are the long history of collaboration between different
      disciplines, the user-centered development approach, the existence of a
      "champion" within the field, and nontechnical community aspects already being in
      place.

PMID- 18725357
TI  - Oral zinc for treating diarrhoea in children.

PMID- 18725356
TI  - Identification and characterization of Arabidopsis indole-3-butyric acid response
      mutants defective in novel peroxisomal enzymes.
AB  - Genetic evidence suggests that indole-3-butyric acid (IBA) is converted to the
      active auxin indole-3-acetic acid (IAA) by removal of two side-chain methylene
      units in a process similar to fatty acid beta-oxidation. Previous studies
      implicate peroxisomes as the site of IBA metabolism, although the enzymes that
      act in this process are still being identified. Here, we describe two IBA
      response mutants, ibr1 and ibr10. Like the previously described ibr3 mutant,
      which disrupts a putative peroxisomal acyl-CoA oxidase/dehydrogenase, ibr1 and
      ibr10 display normal IAA responses and defective IBA responses. These defects
      include reduced root elongation inhibition, decreased lateral root initiation,
      and reduced IBA-responsive gene expression. However, peroxisomal energy
      generating pathways necessary during early seedling development are unaffected in
      the mutants. Positional cloning of the genes responsible for the mutant defects
      reveals that IBR1 encodes a member of the short-chain dehydrogenase/reductase
      family and that IBR10 resembles enoyl-CoA hydratases/isomerases. Both enzymes
      contain C-terminal peroxisomal-targeting signals, consistent with IBA metabolism
      occurring in peroxisomes. We present a model in which IBR3, IBR10, and IBR1 may
      act sequentially in peroxisomal IBA beta-oxidation to IAA.

PMID- 18725358
TI  - Quantifying the potential role of unmeasured confounders: the example of
      influenza vaccination.
AB  - BACKGROUND: The validity of non-randomized studies using healthcare databases is
      often challenged because they lack information on potentially important
      confounders, such as functional health status and socioeconomic status. In a
      study quantifying the effects of influenza vaccination among community-dwelling
      elderly we assessed whether additional information on not routinely available
      covariates was indeed associated with exposure to influenza vaccination and
      could, therefore, have led to residual confounding in healthcare databases.
      METHODS: We randomly selected 500 persons aged 65 years and older from the
      computerized Utrecht General Practitioner database. Information on exposure
      status and on demographics, co-morbidity status, prior healthcare use and
      medication use was extracted from the database. A questionnaire was used to
      obtain additional information on not routinely available risk factors [e.g.
      functional health status (SF-20), smoking status and alcohol consumption].
      Missing data from the questionnaire was imputed and multivariable logistic
      regression analysis was applied to quantify the influence of covariates on the
      prediction of exposure to influenza vaccination. Within an existing dataset the
      potential impact of functional health status on the relation between influenza
      vaccination and mortality was simulated. RESULTS: We obtained questionnaire data
      from 365 of 500 (73%) subjects. The model including routinely available data from
      the database appeared accurate in predicting exposure to influenza vaccination (c
      statistic 0.86, 95% CI: 0.82-0.89). Functional health status was the only
      additional characteristic measured with the questionnaire that was not similar in
      vaccinated and unvaccinated subjects. However, extending the multivariable
      regression model with functional health status did not significantly improve the
      prediction of exposure to influenza vaccination, nor did it affect the relation
      between influenza vaccination and mortality. CONCLUSION: The potential for
      unmeasured confounding on the association between influenza vaccination and
      health outcomes as quantified in healthcare databases seems small for non
      randomized intervention studies within extensive and reliable databases.

PMID- 18725359
TI  - Is the incidence of psychotic disorder in decline? Epidemiological evidence from
      two decades of research.
AB  - BACKGROUND: It is unclear whether the incidence of first episode psychoses is in
      decline. We had the opportunity to determine whether incidence had changed over a
      20-year period in a single setting, and test whether this could be explained by
      demographic or clinical changes. METHODS: The entire population at-risk aged 16
      54 in Nottingham over three time periods (1978-80, 1993-95 and 1997-99) were
      followed up. All participants presenting with an ICD-9/10 first episode psychosis
      were included. The remainder of the population at-risk formed the denominator.
      Standardized incidence rates were calculated at each time period with possible
      change over time assessed via Poisson regression. We studied six outcomes:
      substance-induced psychoses, schizophrenia, other non-affective psychoses, manic
      psychoses, depressive psychoses and all psychotic disorders combined. RESULTS:
      Three hundred and forty-seven participants with a first episode psychosis during
      1.2 million person-years of follow-up over three time periods were identified.
      The incidence of non-affective or affective psychoses had not changed over time
      following standardization for age, sex and ethnicity. We observed a linear
      increase in the incidence of substance-induced psychosis, per annum, over time
      (incidence rate ratios: 1.15; 95% CI 1.05-1.25). This could not be explained by
      longitudinal changes in the age, sex and ethnic structure of the population at
      risk. CONCLUSIONS: Our findings suggest psychotic disorders are not in decline,
      though there has been a change in the syndromal presentation of non-affective
      disorders, away from schizophrenia towards other non-affective psychoses. The
      incidence of substance-induced psychosis has increased, consistent with increases
      in substance toxicity over time, rather than changes in the prevalence or
      vulnerability to substance misuse. Increased clinical and popular awareness of
      substance misuse could also not be excluded.

PMID- 18725360
TI  - Commentary: Ecologic studies in identifying dietary risk factors for coronary
      heart disease and cancer.

PMID- 18725361
TI  - Commentary: Lactose and ischaemic heart disease: a sweet hypothesis ... but
      nothing more!

PMID- 18725362
TI  - Commentary: Lactose and ischaemic heart disease: a weak 28-year-old hypothesis.

PMID- 18725363
TI  - Hypothesis: is lactose a dietary risk factor for ischaemic heart disease?
AB  - The prevalence of primary adult lactose malabsorption (LM) in 23 ethnic groups
      was matched with national data on milk consumption and mortality rates from
      ischaemic heart disease (HD). In 6 other ethnic groups prevalence of LM was
      related to unquantified assessments of milk consumption and frequency of IHD. On
      the available data, populations with a prevalence of LM over 30%, and whose
      consumption of milk is low or is largely in low lactose form, have a lower risk
      of IHD mortality than populations with a prevalence of LM under 30% and a high
      milk consumption. There is evidence against attributing these findings to genetic
      linkage between susceptibility to IHD mortality and persistent lactose
      absorption, or to differences in socio-economic development, cigarette
      consumption or intake of animal fats. The findings are compatible with an
      hypothesis that, if the correlation reported previously between milk consumption
      and IHD mortality is causal, lactose could be the responsible dietary factor.

PMID- 18725364
TI  - Violence, psychological distress and the risk of suicidal behaviour in young
      people in India.
AB  - BACKGROUND: Suicide among young people has emerged as a major public health issue
      in many low- and middle-income (LAMI) countries. Suicidal behaviour including
      ideation and attempt are the most important predictors of completed suicide and
      offer critical points for intervention. The aim of this study is to estimate the
      prevalence and risk factors for suicidal behaviour in young people in India.
      METHOD AND FINDINGS: Cross-sectional study of 3662 youth (16-24 years) from rural
      and urban communities in Goa, India. Suicidal behaviour during the recent 3
      months and associated factors were assessed using a structured interview. Overall
      144; 3.9% [95% confidence interval (CI) 3.3-4.6] youth reported any suicidal
      behaviour in the previous 3 months. Suicidal behaviour was found to be associated
      with female gender Odds ratio (OR) 6.5 (95% CI 3.9-10.8), not attending school or
      college OR 1.6 (95% CI, 1.01-2.6), independent decision making OR 2.5 (95% CI 1.5
      4.3), premarital sex OR 3.2 (95% CI 1.6-6.3), physical abuse at home OR 3.3 (95%
      CI 1.8-6.1), life time experience of sexual abuse OR 3.3 (95% CI 1.8-6.0) and
      probable common mental disorders (CMD) OR 9.5 (95% CI 6.3-14.5). Gender
      segregated analysis found independent decision making (P=0.68 for interaction),
      rural residence (P=0.01 for interaction) and premarital sex (P=0.41 for
      interaction) retained association with suicidal behaviour only among females
      (P<0.05). The population attributable fraction estimates were largest for CMD
      (42.8% for females; 35.9% for males); physical abuse in one's home (12.5% for
      females; 12.4% for males); sexual abuse (12.1% in females; 22.3% in males); and
      making independent decisions (22.9% for females). Analyses of the risk factors
      for the relatively less common outcome of suicide attempts found a similar set of
      factors as for suicidal behaviour; in addition, alcohol use was also an
      independent risk factor. CONCLUSION: Violence and psychological distress are
      independently associated with suicidal behaviour; factors associated with gender
      disadvantage-in particular for rural women, may increase their vulnerabilities.
      Prevention programs for youth suicide in India need to address both the
      structural determinants of gender disadvantage, and the individual experiences of
      violence and poor mental health.

PMID- 18725365
TI  - Commentary: Kristian Feyer Andvord's studies on the epidemiology of tuberculosis
      and the origin of generation cohort analysis.

PMID- 18725366
TI  - Commentary: Kristian Andvord--an under recognized star in the epidemiological
      firmament.

PMID- 18725367
TI  - Commentary: Tuberculosis down the generations--a comment on 'Continued studies of
      Tuberculosis as a generation illness' by Kr F Andvord.

PMID- 18725368
TI  - Commentary: Reconciling historical epidemiological, bacteriological and
      immunological observations in tuberculosis.

PMID- 18725369
TI  - Continued studies of tuberculosis considered as a generation illness. (1932).

PMID- 18725370
TI  - Functional characterization of DEAD-box RNA helicases in Arabidopsis thaliana
      under abiotic stress conditions.
AB  - DEAD-box RNA helicases have been implicated to have a function during stress
      adaptation processes, but their functional roles in plant stress responses remain
      to be clearly elucidated. Here, we assessed the expression patterns and
      functional roles of two RNA helicases, AtRH9 and AtRH25, in Arabidopsis thaliana
      under abiotic stress conditions. The transcript levels of AtRH9 and AtRH25 were
      up-regulated markedly in response to cold stress, whereas their transcript levels
      were down-regulated by salt or drought stress. Phenotypic analysis of the
      transgenic plants and T-DNA-tagged mutants showed that the constitutive
      overexpression of AtRH9 or AtRH25 resulted in the retarded seed germination of
      Arabidopsis plants under salt stress conditions. AtRH25, but not AtRH9, enhanced
      freezing tolerance in Arabidopsis plants. Both AtRH9 and AtRH25 complemented the
      cold-sensitive phenotype of BX04 Escherichia coli mutant cells, but AtRH25 had
      much more prominent complementation ability than AtRH9. An in vitro nucleic acid
      binding assay showed that AtRH9 binds equally to all homoribopolymers, whereas
      AtRH25 binds preferentially to poly(G). Taken together, these results demonstrate
      that AtRH9 and AtRH25 impact on the seed germination of Arabidopsis plants under
      salt stress conditions, and suggest that the difference in cold tolerance
      capability between AtRH9 and AtRH25 arises from their different nucleic acid
      binding properties.

PMID- 18725371
TI  - Effect of serum albumin on serum sodium: necessity to consider the Donnan effect.

PMID- 18725372
TI  - The impact of statin use on atrial fibrillation.
AB  - The aim of the present systematic review is to present an overview of the
      evidence linking atrial fibrillation (AF), inflammation and oxidative stress,
      with emphasis on the potential of statins to decrease the incidence of different
      types of AF, including new-onset AF, after electrical cardioversion (EC) and
      after cardiac surgery. Observational and clinical trials have studied the impact
      of statin therapy on new-onset, post-EC or postoperative AF. Data from different
      observational trials have shown that treatment with statins significantly reduces
      the incidence of new-onset AF in the primary and secondary prevention. The data
      are insufficient to recommend the use of statins before EC. Finally,
      perioperative statin therapy may represent an important non-antiarrhythmic
      adjunctive therapeutic strategy for the prevention of postoperative AF.

PMID- 18725373
TI  - Pyomyositis of the iliacus muscle complicated with septic sacroiliitis.
AB  - We report a rare case of pyomyositis of the iliacus muscle in a 29-year-old
      woman. After 2 weeks of adequate treatment, secondary septic sacroiliitis
      occurred, a complication that had not been described previously. Pyomyositis of
      the iliacus muscle must be considered in the differential diagnosis of acute pain
      in the hip region.

PMID- 18725375
TI  - Covering the uninsured in 2008: current costs, sources of payment, and
      incremental costs.
AB  - People uninsured for any part of 2008 spend about $30 billion out of pocket and
      receive approximately $56 billion in uncompensated care while uninsured.
      Government programs finance about 75 percent of uncompensated care. If all
      uninsured people were fully covered, their medical spending would increase by
      $122.6 billion. The increase represents 5 percent of current national health
      spending and 0.8 percent of gross domestic product. However, it is neither the
      cost of a specific plan nor necessarily the same as the government's costs, which
      could be higher, depending on plans' financing structures and the extent of crowd
      out.

PMID- 18725374
TI  - The psoriatic arthritis cost evaluation study: a cost-of-illness study on tumour
      necrosis factor inhibitors in psoriatic arthritis patients with inadequate
      response to conventional therapy.
AB  - OBJECTIVE: To evaluate costs, benefits and cost-effectiveness of anti-TNF agents
      in PsA patients with inadequate response to conventional treatment. METHODS: A
      total of 107 patients, from nine Italian rheumatology centres, with different
      forms of PsA were given anti-TNF treatment, mainly etanercept (87%). Information
      on resource use, health-related quality of life, disease activity, function and
      laboratory values were collected at baseline and through out the 12 months of
      therapy. Cost (expressed in euro 2007) and utility (measured by EuroQol) before
      and after anti-TNF therapy initiation were compared in order to estimate the
      incremental cost per quality-adjusted life year (QALY) gained, and cost
      effectiveness acceptability curve was calculated. RESULTS: At the end of 12
      months, there was a significant increase in direct cost due to an increase of
      drug cost caused by TNF inhibitors that was only partially offset by the decrease
      in indirect cost. In the last 6 months of therapy, the direct cost increased by
      euro5052, the cost for the National Health System (NHS) by euro5044 and the
      social cost by euro4638. However, a gain of 0.12 QALY resulted in a cost per QALY
      gained of euro40 876 for the NHS and of euro37 591 for the society. The
      acceptability curve showed that there would be a 97% likelihood that anti-TNF
      therapy would be considered cost-effective at willingness-to-pay threshold of
      euro60 000 per QALY gained. CONCLUSION: Cost-effectiveness ratios are within the
      commonly accepted willingness-to-pay threshold. These results need to be
      confirmed in larger samples of patients.

PMID- 18725377
TI  - Identification of target genes for a MYB-type anthocyanin regulator in Gerbera
      hybrida.
AB  - Genetic modification of the flavonoid pathway has been used to produce novel
      colours and colour patterns in ornamental plants as well as to modify the
      nutritional and pharmaceutical properties of food crops. It has been suggested
      that co-ordinate control of multiple steps of the pathway with the help of
      regulatory genes would lead to a more predictable control of metabolic flux.
      Regulation of anthocyanin biosynthesis has been studied in a common ornamental
      plant, Gerbera hybrida (Asteraceae). An R2R3-type MYB factor, GMYB10, shares high
      sequence similarity and is phylogenetically grouped together with previously
      characterized regulators of anthocyanin pigmentation. Ectopic expression of
      GMYB10 leads to strongly enhanced accumulation of anthocyanin pigments as well as
      to an altered pigmentation pattern in transgenic gerbera plants. Anthocyanin
      analysis indicates that GMYB10 specifically induces cyanidin biosynthesis in
      undifferentiated callus and in vegetative tissues. Furthermore, in floral tissues
      enhanced pelargonidin production is detected. Microarray analysis using the
      gerbera 9K cDNA array revealed a highly predicted set of putative target genes
      for GMYB10 including new gene family members of both early and late biosynthetic
      genes of the flavonoid pathway. However, completely new candidate targets, such
      as a serine carboxypeptidase-like gene as well, as two new MYB domain factors,
      GMYB11 and GMYB12, whose exact function in phenylpropanoid biosynthesis is not
      clear yet, were also identified.

PMID- 18725376
TI  - Vascular calcifications, vertebral fractures and mortality in haemodialysis
      patients.
AB  - BACKGROUND: Vascular calcifications and the bone fractures caused by abnormal
      bone fragility, also called osteoporotic fractures, are frequent complications
      associated with chronic kidney diseases (CKD). The aim of this study was to
      investigate the association between vascular calcifications, osteoporotic bone
      fractures and survival in haemodialysis (HD) patients. METHODS: A total of 193 HD
      patients were followed up to 2 years. Vascular calcifications and osteoporotic
      vertebral fractures (quoted just as vertebral fractures in the text) were
      assessed by thoracic, lumbar spine, pelvic and hand X-rays and graded according
      to their severity. Clinical, biochemical and therapeutic data gathered during the
      total time spent on HD were collected. RESULTS: The prevalence of aortic
      calcifications was higher in HD patients than in a random-based general
      population (79% versus 37.5%, P < 0.001). Total time on any renal replacement
      therapy (RRT) and diabetes were positively associated with a higher prevalence of
      vascular calcifications. In addition to these factors, time on HD was also
      positively associated with the severity of vascular calcifications, and higher
      haemoglobin levels were associated with a lower prevalence of severe vascular
      calcifications in large and medium calibre arteries. The prevalence of vertebral
      fractures in HD patients was similar to that of the general population (26.5%
      versus 24.1%). Age and time on HD showed a positive and statistically significant
      association with the prevalence of vertebral fractures. Vascular calcifications
      in the medium calibre arteries were associated with a higher rate of prevalent
      vertebral fractures. In women, severe vascular calcifications and vertebral
      fractures were positively associated with mortality [RR = 3.2 (1.0-10.0) and RR =
      4.8 (1.7-13.4), respectively]. CONCLUSIONS: Positive associations between
      vascular calcifications, vertebral fractures and mortality have been found in
      patients on HD.

PMID- 18725378
TI  - Phospholipase A2beta mediates light-induced stomatal opening in Arabidopsis.
AB  - Phospholipase A(2) (PLA(2)) catalyses the hydrolysis of phospholipids into
      lysophospholipids and free fatty acids. Physiological studies have indicated that
      PLA(2) is involved in stomatal movement. However, genetic evidence of a role of
      PLA(2) in guard cell signalling has not yet been reported. To identify PLA(2)
      gene(s) that is (are) involved in light-induced stomatal opening, stomatal
      movement was examined in Arabidopsis thaliana plants in which the expression of
      PLA(2) isoforms was reduced or knocked-out. Light-induced stomatal opening in
      PLA(2)alpha knockout plants did not differ from wild-type plants. Plants in which
      PLA(2)beta was silenced by RNA interference exhibited delayed light-induced
      stomatal opening, and this phenotype was reversed by exogenous lysophospholipids,
      which are products of PLA(2). Stomatal opening in transgenic plants that over
      expressed PLA(2)beta was faster than wild-type plants. The expression of
      PLA(2)beta was localized to the endoplasmic reticulum of guard cells, and
      increased in response to light in the mature leaf. Aristolochic acid, which
      inhibits light-induced stomatal opening, inhibited the activity of purified
      PLA(2)beta. Collectively, these results provide evidence that PLA(2)beta is
      involved in light-induced stomatal opening in Arabidopsis.

PMID- 18725379
TI  - Lessons from recent accidents in radiation therapy in France.
AB  - Many accidents in radiotherapy have been reported in France over the last years.
      This is due to the recent legal obligation to declare to the national safety
      authorities any significant incident relative to the use of ionising radiation
      including medical applications. The causes and consequences of the most serious
      events in radiotherapy are presented in this paper. Lessons can be learned from
      possible technical dysfunctions, from human errors or organisational weaknesses
      as to how such events can be prevented. The technical aspects are addressed here:
      in particular, dosimetric issues.

PMID- 18725380
TI  - Analysis of computational problems expressing the overall uncertainties: photons,
      neutrons and electrons.
AB  - In the frame of the EU Coordination Action CONRAD (coordinated network for
      radiation dosimetry), WP4 was dedicated to work on computational dosimetry with
      an action entitled 'Uncertainty assessment in computational dosimetry: an
      intercomparison of approaches'. Participants attempted one or more of eight
      problems. This paper presents the results from problems 4-8-dealing with the
      overall uncertainty budget estimate; a short overview of each problem is
      presented together with a discussion of the most significant results and
      conclusions. The scope of the problems discussed here are: the study of a (137)Cs
      calibration irradiator; the manganese bath technique; the iron sphere experiment
      using neutron time-of-flight technique; the energy response of a RADFET detector
      and finally the sensitivity and uncertainty analysis for the recoil-proton
      telescope discussed in the companion paper.

PMID- 18725381
TI  - Bladder cancer risks in workers manufacturing chemicals for the rubber industry.
AB  - AIM: To investigate bladder cancer risks in workers from a factory manufacturing
      chemicals for the rubber industry. METHODS: The mortality (1955-2005) and cancer
      morbidity experience (1971-2005) of a cohort of 2160 male production workers from
      a chemical factory in north Wales were investigated. Exposure estimates (or
      surrogates) were developed for four chemicals: 2-mercaptobenzothiazole (MBT),
      aniline, phenyl-beta-naphthylamine (PBN) and ortho-toluidine. Two analytical
      approaches were used, indirect standardization and Poisson regression. RESULTS:
      Based on mortality rates for the general population, there was a statistically
      significant (P < 0.01) excess mortality from bladder cancer in the 611 study
      subjects potentially exposed to one or more of the four chemicals being
      investigated (observed 11, standardized mortality ratio 278, 95% confidence
      interval 139-497). There was no excess bladder cancer mortality in the remaining
      1555 workers. A similar contrast was also shown for bladder cancer incidence.
      There were 56 study subjects who had suffered from bladder cancer (malignant or
      benign). In simultaneous analyses of the four exposure history variables, Poisson
      regression showed a significant positive trend for bladder cancer risk in
      relation to cumulative duration of employment in the ortho-toluidine department
      (P < 0.05) and non-significant positive trends in relation to cumulative duration
      of employment in the PBN department and to cumulative exposure to MBT.
      CONCLUSIONS: Some members of this cohort have suffered from occupational bladder
      cancer. Exposure to ortho-toluidine appears to be responsible for part of this
      excess and the manufacture of PBN and exposure to MBT may also have been
      involved.

PMID- 18725382
TI  - Does exercise cause asthma?
AB  - BACKGROUND: The Israel Defence Forces needed to define the correlation between
      physical activity and asthma. AIM: To determine whether combat unit (CU) soldiers
      are more susceptible to exercise-induced asthma (EIA) than other military units.
      METHODS: A follow-up study of recruits with normal clinical and pulmonary
      function tests over a period of 30 months after having been assigned to CU,
      maintenance units (MU) or clerical tasks (CT). The participants chosen had
      already been subjected to additional tests 6 weeks after induction to eliminate
      any cases of active asthma. RESULTS: Out of 799 subjects, 125 developed asthma
      during the follow-up. Twenty-one per cent of those in the CU developed asthma
      against 15% in the MU and 5% in the CT. The relative risks for newly diagnosed
      asthma were 3.7 for CU/CT (P < 0.001), 2.7 for MU/CT (P < 0.001) and 1.4 for
      CU/MU (P < 0.05). EIA was observed as the only manifestation of asthma in 32% of
      the soldiers posted in CU compared to 13 and 11% in MU and CT, respectively.
      CONCLUSION: The increased risk of EIA in CU compared to MU and CT may indicate
      that any one or all the factors associated with CU service conditions could
      contribute to this increased risk of uncovering the mild cases of asthma,
      especially EIA, that had been overlooked up to the time of induction into the
      army.

PMID- 18725383
TI  - Cephalometric evaluation of Class II malocclusion treatment with cervical
      headgear and mandibular fixed appliances.
AB  - The present study aimed to evaluate the cephalometric changes in Class II
      patients treated exclusively with cervical headgear (CHG) in the maxillary arch
      and fixed appliances in the mandibular arch as compared with a control group. The
      sample comprised 82 lateral cephalograms obtained pre- (T1) and post- (T2)
      treatment/observation of 41 subjects, divided into two groups: group 1-25 Class
      II division 1 patients (20 females and five males), with a mean pre-treatment age
      of 10.4 years, treated for a mean period of 2.5 years and group 2-16 Class II
      untreated subjects (12 females and four males), with a mean initial age of 9.9
      years, followed for a mean period of 2.2 years. Treatment changes between the
      groups were compared by means of t-tests. The results showed restriction of
      maxillary forward displacement and also a restriction in maxillary length growth,
      improvement in the maxillomandibular relationship, restriction of mandibular
      incisor vertical development, reduction in overjet and overbite, and improvement
      in molar relationship. It was concluded that this treatment protocol corrected
      the Class II malocclusion characteristics primarily through maxillary forward
      growth restriction.

PMID- 18725384
TI  - Estimation of nucleotide diversity, disequilibrium coefficients, and mutation
      rates from high-coverage genome-sequencing projects.
AB  - Recent advances in sequencing strategies have made it feasible to rapidly obtain
      high-coverage genomic profiles of single individuals, and soon it will be
      economically feasible to do so with hundreds to thousands of individuals per
      population. While offering unprecedented power for the acquisition of population
      genetic parameters, these new methods also introduce a number of challenges, most
      notably the need to account for the binomial sampling of parental alleles at
      individual nucleotide sites and to eliminate bias from various sources of
      sequence errors. To minimize the effects of both problems, methods are developed
      for generating nearly unbiased and minimum-sampling-variance estimates of a
      number of key parameters, including the average nucleotide heterozygosity and its
      variance among sites, the pattern of decomposition of linkage disequilibrium with
      physical distance, and the rate and molecular spectrum of spontaneously arising
      mutations. These methods provide a general platform for the efficient utilization
      of data from population-genomic surveys, while also providing guidance for the
      optimal design of such studies.

PMID- 18725385
TI  - Cox-2 inactivates Smad signaling and enhances EMT stimulated by TGF-beta through
      a PGE2-dependent mechanisms.
AB  - Although it is well established that mammary tumorigenesis converts transforming
      growth factor-beta (TGF-beta) from a tumor suppressor to a tumor promoter, the
      molecular, cellular and microenvironmental mechanisms underlying the dichotomous
      nature of TGF-beta in mammary epithelial cells (MECs) remains to be determined
      definitively. Aberrant upregulation of the inducible cyclooxygenase, Cox-2,
      occurs frequently in breast cancers and is associated with increasing disease
      severity and the acquisition of metastasis; however, the impact of Cox-2
      expression on normal and malignant MEC response to TGF-beta remains unknown. We
      show here that TGF-beta induced Cox-2 expression in normal MECs during their
      acquisition of an epithelial-mesenchymal transition (EMT) phenotype. Moreover,
      stable Cox-2 expression in normal MECs stimulated their invasion, EMT and
      anchorage-independent growth and inhibited their activation of Smad2/3 by TGF
      beta. Conversely, antagonizing TGF-beta signaling in malignant, metastatic MECs
      significantly reduced their expression of Cox-2 as well as enhanced their
      activation of Smad2/3 by TGF-beta. Along these lines, elevated Cox-2 expression
      elicited prostaglandin E(2) (PGE(2)) production and the autocrine activation of
      EP receptors, which antagonized Smad2/3 signaling in normal and malignant MECs.
      Importantly, rendering normal and malignant MECs Cox-2 deficient inhibited their
      production of PGE(2) and acquisition of an EMT morphology as well as potentiated
      their nuclear accumulation of Smad2/3 and transcription of plasminogen activator
      inhibitor-1 and p15 messenger RNA. Collectively, our findings establish Cox-2 as
      a novel antagonist of Smad2/3 signaling in normal and malignant MECs; they also
      suggest that chemotherapeutic targeting of Cox-2 may offer new inroads in
      restoring the tumor-suppressing activities of TGF-beta in malignant, metastatic
      breast cancers.

PMID- 18725386
TI  - Plant flavonoid apigenin inactivates Akt to trigger apoptosis in human prostate
      cancer: an in vitro and in vivo study.
AB  - Inappropriate activation of phosphatidylinositol 3-kinase-Akt signaling
      contributes to the development of several human malignancies. Modulation of Akt
      activity is a strategy that may be valuable in chemopreventive and
      chemotherapeutic regimens. We have previously demonstrated that apigenin, a plant
      flavone, causes decreased survival in human prostate cancer cells. However, the
      molecular mechanism underlying this observation remains elusive. In the present
      study, we investigated the mechanisms of apigenin action on human prostate cancer
      PC-3 cells, which possess constitutively active Akt. Treatment of PC-3 cells with
      apigenin (5-40 microM) resulted in significant dose- and time-dependent decrease
      in Akt phosphorylation at Serine473. Apigenin-mediated dephosphorylation of Akt
      resulted in inhibition of its kinase activity, which was confirmed by reduced
      phosphorylation of proapoptotic proteins BAD and glycogen synthase kinase-3,
      essential downstream targets of Akt. Hypophosphorylation of BAD resulted in
      reduced interaction with 14-3-3beta protein after 20 microM apigenin exposure to
      PC-3 cells for 24 h. Inactivation of Akt seems to be associated with
      downregulation of insulin-like growth factor receptor 1 protein level and
      inhibition of its autophosphorylation upon apigenin treatment. Exposure to
      apigenin significantly induced caspase-9 activity and decreased the survival of
      PC-3 cells in a dose-dependent manner. Furthermore, Serine473 phosphorylation of
      ectopically expressed Akt in DU145 cells was significantly reduced upon 20 microM
      apigenin treatment. In vivo, apigenin intake through gavage resulted in
      inactivation of Akt and induction of apoptosis in PC-3 tumors. These results
      suggest that Akt inactivation and dephosphorylation of BAD is a critical event,
      at least in part, in apigenin-induced decreased cell survival and apoptosis.

PMID- 18725387
TI  - YAP1 is involved in mesothelioma development and negatively regulated by Merlin
      through phosphorylation.
AB  - We previously reported the results of bacterial artificial chromosome array
      comprehensive genomic hybridization of malignant pleural mesotheliomas (MPMs),
      including two cases with high-level amplification in the 11q22 locus. In this
      study, we found that the YAP1 gene encoding a transcriptional coactivator was
      localized in this amplified region and overexpressed in both cases, suggesting it
      as a candidate oncogene in this region. We analyzed the involvement of YAP1 in
      MPM proliferation, as well as its functional and physical interaction with Merlin
      encoded by the neurofibromatosis type 2 (NF2) tumor suppressor gene, which is
      frequently mutated in MPMs. YAP1-RNA interference suppressed growth of a
      mesothelioma cell line NCI-H290 with NF2 homozygous deletion, probably through
      cell-cycle arrest and apoptosis induction, whereas YAP1 transfection promoted the
      growth of MeT-5A, an immortalized mesothelial cell line. We also found that the
      introduction of NF2 into NCI-H290 induced phosphorylation at serine 127 of YAP1,
      which was accompanied by reduction of nuclear localization of YAP1, whereas
      nuclear localization of a YAP1 S 127A mutant was not affected. Furthermore,
      results of immunoprecipitation and in vitro pull-down assays indicated a physical
      interaction between Merlin and YAP1. These results suggest that YAP1 is involved
      in mesothelial cell growth and that the transcriptional coactivator activity of
      YAP1 is functionally inhibited by Merlin through the induction of phosphorylation
      and cytoplasmic retention of YAP1. This is the first report of negative
      regulatory signaling from Merlin to YAP1 in mammalian cells. Future studies of
      transcriptional targets of YAP1 in MPMs may shed light on the molecular
      mechanisms of MPM development and lead to new therapeutic strategies.

PMID- 18725388
TI  - Comparing nose-throat swabs and nasopharyngeal aspirates collected from children
      with symptoms for respiratory virus identification using real-time polymerase
      chain reaction.
AB  - OBJECTIVES: The objective of this study was to calculate sensitivity values for
      the detection of major respiratory viruses of childhood by using combined nose
      throat swabs and nasopharyngeal aspirates. METHODS: Children who had symptoms and
      presented to a pediatric teaching hospital and had a diagnostic respiratory
      specimen collected were enrolled, and paired nose-throat swab and nasopharyngeal
      aspirate specimens were collected. Parents were asked to collect the nose-throat
      swab specimen in the first instance but could defer to a health care worker if
      unwilling. Nose-throat swab collectors were asked to rate perceived quality of
      collection. All nasopharyngeal aspirates were collected by a health care worker
      by using a standard protocol. Real-time polymerase chain reaction for 8
      respiratory viruses was performed in our hospital's diagnostic laboratory.
      RESULTS: Paired nose-throat swab/nasopharyngeal aspirate specimens were collected
      during 303 illnesses, with at least 1 respiratory virus identified in 186 (61%).
      For the major pathogens of childhood, influenza A virus and respiratory syncytial
      virus, collection by using the nose-throat swab had a sensitivity of 91.9% and
      93.1%, respectively. A health care worker collected 219 (72%) of the nose-throat
      swab specimens; concordance with the nasopharyngeal aspirate was not related to
      health care worker collection or perceived quality of collection. CONCLUSIONS:
      Nose-throat swab specimens, in combination with sensitive molecular testing, are
      a less invasive diagnostic respiratory specimen with adequate sensitivity for use
      in the clinic and hospital outpatient settings and large-scale community studies
      through parent collection. For children who present to a hospital in which an
      avian or pandemic strain of influenza virus is reasonably part of the
      differential diagnosis, nasopharyngeal aspirates or a similar collection
      technique (eg, nasal washes) should continue to be used.

PMID- 18725389
TI  - Free radical injury and blood-brain barrier permeability in hypoxic-ischemic
      encephalopathy.
AB  - OBJECTIVES: The purpose of this work was to evaluate the extent of free radical
      injury in newborns with hypoxic ischemic encephalopathy by measuring plasma
      levels of malondialdehyde and nitric oxide and to assess the blood-brain barrier
      permeability by measuring the cerebrospinal fluid albumin/plasma albumin ratio.
      METHODS: This prospective observational study was conducted over a period of 2
      years at Sir Sundarlal Hospital, Banaras Hindu University. The study population
      consisted of 43 term neonates with perinatal asphyxia who subsequently developed
      hypoxic ischemic encephalopathy. Twenty normal gestational age- and gender
      matched healthy infants without any perinatal asphyxia served as control
      subjects. Peripheral venous blood samples were analyzed for malondialdehyde,
      total plasma nitrates/nitrites, and albumin levels between 12 and 24 hours of
      life. To assess the blood-brain barrier permeability, the cerebrospinal fluid
      albumin/plasma albumin ratio was measured. Correlation among the levels of
      malondialdehyde, nitrates/nitrites, and blood-brain barrier permeability was
      calculated. Data were analyzed by using SPSS 10 software. RESULTS: Plasma
      malondialdehyde and nitrate/nitrite levels were significantly higher in infants
      with hypoxic ischemic encephalopathy compared with control subjects. Although
      there was a progressive increment in plasma levels of malondialdehyde with
      increasing severity of hypoxic ischemic encephalopathy, the differences were not
      statistically significant. Plasma nitrate/nitrite levels were almost similar in
      all stages of hypoxic ischemic encephalopathy. Plasma albumin levels were
      comparable in infants with hypoxic ischemic encephalopathy and control subjects,
      whereas cerebrospinal fluid albumin levels and blood-brain barrier permeability
      were significantly higher in infants with hypoxic ischemic encephalopathy.
      Significant correlation was observed between plasma malondialdehyde and
      nitrate/nitrite levels with blood-brain barrier permeability. CONCLUSIONS:
      Increased plasma levels of malondialdehyde and nitrates/nitrites are found to be
      associated with hypoxic ischemic encephalopathy, indicating the possible role of
      free radical injury in its causation. Increased blood-brain barrier permeability
      may be another contributory factor to the progression of the disease.

PMID- 18725390
TI  - The role of secondary cytoreduction in the management of the first relapse in
      epithelial ovarian cancer.
AB  - BACKGROUND: The aim of this study was to investigate the benefit of secondary
      cytoreduction (SCR) in the first relapse in epithelial ovarian cancer and to
      attempt to define selection criteria for SCR. PATIENTS AND METHODS: A
      retrospective population-based study on recorded information from 789 patients
      treated at the Norwegian Radium Hospital during 1985-2000 for their initial
      recurrence. In all, 217 had SCR and 572 were treated with chemotherapy alone.
      RESULTS: Median survival time (MST) was 1.1 years for the chemotherapy group.
      Complete optimal cytoreduction (COC) was achieved in 35% of all 217 patients, in
      49% of the patients operated with debulking intent and in 52% if bowel surgery
      was done with debulking intent. MST was 4.5 versus 0.7 years for 0 versus>2 cm
      residual disease, respectively. Residual disease after SCR, treatment-free
      interval (TFI) and age were found to be prognostic factors for overall survival
      (OS) in multivariate analysis. Localised tumour was found to be the only
      significant factor to predict COC. CONCLUSIONS: SCR followed by chemotherapy
      gives a clear survival benefit compared with chemotherapy and should be offered
      when the tumour is localised. The combination of COC, TFI >24 months and age
      </=39 years identifies a group of patients with the best OS.

PMID- 18725391
TI  - Estrogens, oral contraceptives and hormonal replacement therapy increase the
      incidence of cutaneous melanoma: a population-based case-control study.
AB  - BACKGROUND: Multiple studies showed conflicting results on the association
      between oral contraceptive (OC) use and the development of cutaneous melanoma
      (CM). We investigated the association between estrogen use and CM incidence.
      PATIENTS AND METHODS: Data from PHARMO Pharmacy database and PALGA, the pathology
      database in The Netherlands, were linked. Women, >or=18 years, with a pathology
      report of a primary CM from 1 January 1991 to 14 December 2004 and >or=3 years of
      follow-up before CM diagnosis were eligible cases. Controls were matched for age
      and geographic region. Multivariate logistic regression was used to calculate
      adjusted odds ratio (OR) and 95% confidence interval (CI) for the association
      between CM incidence and estrogen use, OCs and hormonal replacement therapy
      (HRT), separately. RESULTS: In total, 778 cases and 4072 controls were included.
      CM risk was significantly associated with estrogen use (>or=0.5 year; adjusted OR
      = 1.42, 95% CI 1.19-1.69). This effect was cumulative dose dependent (P trend <
      0.001). CM risk was also significantly associated with the use of HRT (>or=0.5
      year: OR = 2.08; 95% CI 1.37-3.14) and OC (>or=0.5 year: OR = 1.28; 95% CI 1.06
      1.54). CONCLUSION: Our study suggests a cumulative dose-dependent increased risk
      of CM with the use of estrogens.

PMID- 18725392
TI  - Cancer in adolescents and young adults in north Netherlands (1989-2003):
      increased incidence, stable survival and high incidence of second primary
      tumours.
AB  - BACKGROUND: Lack of survival improvement in adolescents and young adults (AYA)
      with cancer has led to increased awareness of this young population. DESIGN: We
      carried out a population-based study of incidence and survival of primary tumours
      and second primary tumours in patients aged 12-24 in north Netherlands. Age
      specific incidence rates per 100,000 and 3-year moving means were calculated.
      Factors associated with incidence and survival were assessed using a Poisson
      model, log-rank test and multivariate Cox proportional hazards analysis. RESULTS:
      From 1989 to 2003 a total of 1118 patients were diagnosed. The total age-specific
      incidence rates per 100,000 were as follows: males: 13.4 (12-15 years), 26.9 (16
      19 years) and 27.5 (20-24 years) and females: 13.9, 20.7 and 20.7. Male : female
      ratio was 1.32. The overall estimated annual percentage change (EAPC) in
      incidence was 2.15% (P < 0.01). Five-year survival was 80.8% and did not improve
      during the study period. With median follow-up of 5.5 years (range 0.0-16.0) in
      our cohort the standardized incidence ratio (SIR) of second primary tumours was
      30.55 (95% confidence interval = 19.96-44.76, P < 0.05). CONCLUSIONS: The total
      incidence of cancer in AYA increased (EAPC = 2.15%). Survival was unchanged. The
      SIR of a second primary tumour in this young cohort increased 31-fold. Further
      research is needed to study this increasing incidence and optimise treatment
      outcome in these young patients.

PMID- 18725393
TI  - Loss of enterocyte mass is accompanied by diminished turnover of enterocytes
      after myeloablative therapy in haematopoietic stem-cell transplant recipients.
AB  - BACKGROUND: Intestinal mucosal barrier injury (MBI), resulting from myeloablative
      conditioning for haematopoietic stem-cell transplantation (HSCT), is an important
      cause of morbidity. Despite its frequency, recognition presents a challenge,
      while the aetiology needs still to be unravelled. The relationship between
      enterocyte mass and enterocyte loss was explored by examining citrulline serum
      levels and by assessing circulating intestinal fatty acid-binding protein (I
      FABP) and ileal bile acid-binding protein (I-BABP), proteins released by dying
      mature enterocytes. PATIENTS AND METHODS: Thirty-four adult patients with
      haematological malignancy received allogeneic HSCT (HSCT day 0) 12 days after
      being given idarubicin, cyclophosphamide and total body irradiation as
      myeloablative conditioning, a regimen known to induce oral and intestinal MBI.
      Serum levels of citrulline, I-FABP and I-BABP were measured on HSCT days -12, -6,
      0, +7, +14 and +21. RESULTS: Myeloablative conditioning resulted in a significant
      decrease in serum citrulline with the nadir on HSCT day +7; thereafter, levels
      rose gradually. Simultaneously, a significant decrease in I-FABP and I-BABP
      levels occurred from the day of transplant until day +14. CONCLUSIONS:
      Simultaneous reduction and subsequent increase of citrulline and I-FABP and I
      BABP levels following cytotoxic treatment show that enterocyte mass corresponds
      to lower rate of dying enterocytes, indicating reduced turnover of enterocytes.
      Assessment of enterocyte turnover and mass offers opportunities for evaluation of
      new MBI therapies.

PMID- 18725394
TI  - The broad effects of the functional IL-10 promoter-592 polymorphism: modulation
      of IL-10, TIMP-3, and OPG expression and their association with periodontal
      disease outcome.
AB  - Periodontal diseases are infectious diseases, in which periodontopathogens
      trigger chronic inflammatory and immune responses that lead to tissue
      destruction. It occurs through the generation of metalloproteinases and the
      activation of bone resorption mechanisms. Anti-inflammatory cytokines such as IL
      10 seem to attenuate periodontal tissue destruction through the induction of
      tissue inhibitors of metalloproteinases (TIMPs) and the inhibitor of
      osteoclastogenesis osteoprotegerin (OPG). A high individual variation in levels
      of IL-10 mRNA is verified in periodontitis patients, which is possibly determined
      by genetic polymorphisms. In this study, the IL-10 promoter -592C/A single
      nucleotide polymorphism (SNP), which is associated with a decrease in IL-10
      production, was analyzed by RFLP in 116 chronic periodontitis (CP) patients and
      173 control (C) subjects, and the IL-10, TIMPs, and OPG mRNA expression levels in
      diseased gingival tissues were determined by real-time-PCR. The IL-10-592 SNP CA
      (P=0.0012/OR=2.4/CI:1.4-4.1), AA (P=0.0458/OR=2.3/CI:1.1-4.9), and CA+AA
      (P=0.0006/OR=2.4/CI:1.4-3.4) genotypes and the allele A (P=0.0036/OR=1.7/CI:1.2
      2.4) were found to be significantly more prevalent in the CP group when compared
      with control subjects. Both CA and AA genotypes were associated with lower levels
      of IL-10, TIMP-3, and OPG mRNA expression in diseased periodontal tissues and
      were also associated with disease severity as mean pocket depth. Taken together,
      the results presented here demonstrate that IL10-592 SNP is functional in CP,
      being associated with lower levels of IL-10 mRNA expression, which is supposed to
      consequently decrease the expression of the downstream genes TIMP-3 and OPG, and
      influence periodontal disease outcome.

PMID- 18725395
TI  - Human dendritic cells differentiated in hypoxia down-modulate antigen uptake and
      change their chemokine expression profile.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells and fine-tune
      the immune response. We have investigated hypoxia's effects on the
      differentiation and maturation of DCs from human monocytes in vitro, and have
      shown that it affects DC functions. Hypoxic immature DCs (H-iDCs) significantly
      fail to capture antigens through down-modulation of the RhoA/Ezrin-Radixin-Moesin
      pathway and the expression of CD206. Moreover, H-iDCs released higher levels of
      CXCL1, VEGF, CCL20, CXCL8, and CXCL10 but decreased levels of CCL2 and CCL18,
      which predict a different ability to recruit neutrophils rather than monocytes
      and create a proinflammatory and proangiogenic environment. By contrast, hypoxia
      has no effect on DC maturation. Hypoxic mature DCs display a mature phenotype and
      activate both allogeneic and specific T cells like normoxic mDCs. This study
      provides the first demonstration that hypoxia inhibits antigen uptake by DCs and
      profoundly changes the DC chemokine expression profile and may have a critical
      role in DC differentiation, adaptation, and activation in inflamed tissues.

PMID- 18725396
TI  - Characterization of phenotypically distinct B-cell subsets and receptor
      stimulated mitogen-activated protein kinase activation in human cord blood B
      cells.
AB  - Human cord blood (CB) is a valuable source of hematopoietic stem cells, but
      clinical reports have indicated slow recovery of B-cell development and function
      after CB transplantation. To investigate the basis of these B-cell defects in
      reconstitution, we characterized B cells purified from CB. We compared B-cell
      receptor activation and B-cell subsets in CB, bone marrow (BM), and peripheral
      blood (PB). We found that in CB B cells activation of extracellular signal
      regulated kinase (ERK) and p38 following ligation of CD40 but not of the B-cell
      antigen receptor (BCR) was inefficient. The patterns of expression of CD5, CD34,
      and CD40 in the B-cell population of CB were similar to those in PB rather than
      in BM. The B cells in CB contained an increased proportion of B cells expressing
      a high level of CD24 and a low proportion of B cells expressing CD27, pointing to
      the presence of circulating CD24high immature transitional and CD27(-) naive B
      cells. CD40-mediated activation of ERK and p38 was also minimal in these B cells
      of CB. These findings may account for the functional defects of B cells in
      transplanted CB.

PMID- 18725397
TI  - The in vivo mitochondrial two-step maturation of human frataxin.
AB  - Deficiency in the nuclear-encoded mitochondrial protein frataxin causes
      Friedreich ataxia (FRDA), a progressive neurodegenerative disorder associating
      spinocerebellar ataxia and cardiomyopathy. Although the exact function of
      frataxin is still a matter of debate, it is widely accepted that frataxin is a
      mitochondrial iron chaperone involved in iron-sulfur cluster and heme
      biosynthesis. Frataxin is synthesized as a precursor polypeptide, directed to the
      mitochondrial matrix where it is proteolytically cleaved by the mitochondrial
      processing peptidase to the mature form via a processing intermediate. The mature
      form was initially reported to be encoded by amino acids 56-210 (m(56)-FXN).
      However, two independent reports have challenged these studies describing two
      different forms encoded by amino acids 78-210 (m(78)-FXN) and 81-210 (m(81)-FXN).
      Here, we provide evidence that mature human frataxin corresponds to m(81)-FXN,
      and can rescue the lethal phenotype of fibroblasts completely deleted for
      frataxin. Furthermore, our data demonstrate that the migration profile of
      frataxin depends on the experimental conditions, a behavior which most likely
      contributed to the confusion concerning the endogenous mature frataxin.
      Interestingly, we show that m(56)-FXN and m(78)-FXN can be generated when the
      normal maturation process of frataxin is impaired, although the physiological
      relevance is not clear. Furthermore, we determine that the d-FXN form, previously
      reported to be a degradation product, corresponds to m(78)-FXN. Finally, we
      demonstrate that all frataxin isoforms are generated and localized within the
      mitochondria. The clear identification of the N-terminus of mature FXN is an
      important step for designing therapeutic approaches for FRDA based on frataxin
      replacement.

PMID- 18725398
TI  - The role of violence in street crime: a qualitative study of violent offenders.
AB  - Studies on the motivation for violent street crime, such as robbery and assault,
      have tended to draw on either the rational choice or the subcultural perspective.
      This study explores the extent to which violence on the street can be explained
      by rational factors associated with the successful commission of the offence or
      social factors related to street culture. The study is based on qualitative
      interviews with 55 violent street offenders who were serving sentences for street
      robbery and assault in six prisons in the United Kingdom. The findings, based on
      accounts of 101 incidents of street violence, identified four main explanations
      for street violence: (a) successful offence enactment, (b) buzz and excitement,
      (c) status and honor, and (d) informal justice. The article concludes that there
      might be benefits in combining the insights of both perspectives by generating an
      integrated theory that would properly explain both the rational and the seemingly
      irrational components of street violence.

PMID- 18725399
TI  - A direct interaction between the Utp6 half-a-tetratricopeptide repeat domain and
      a specific peptide in Utp21 is essential for efficient pre-rRNA processing.
AB  - The small subunit (SSU) processome is a ribosome biogenesis intermediate that
      assembles from its subcomplexes onto the pre-18S rRNA with yet unknown order and
      structure. Here, we investigate the architecture of the UtpB subcomplex of the
      SSU processome, focusing on the interaction between the half-a-tetratricopeptide
      repeat (HAT) domain of Utp6 and a specific peptide in Utp21. We present a
      comprehensive map of the interactions within the UtpB subcomplex and further show
      that the N-terminal domain of Utp6 interacts with Utp18 while the HAT domain
      interacts with Utp21. Using a panel of point and deletion mutants of Utp6, we
      show that an intact HAT domain is essential for efficient pre-rRNA processing and
      cell growth. Further investigation of the Utp6-Utp21 interaction using both
      genetic and biophysical methods shows that the HAT domain binds a specific
      peptide ligand in Utp21, the first example of a HAT domain peptide ligand, with a
      dissociation constant of 10 muM.

PMID- 18725400
TI  - Poly(A)-binding protein-interacting protein 1 binds to eukaryotic translation
      initiation factor 3 to stimulate translation.
AB  - Poly(A)-binding protein (PABP) stimulates translation initiation by binding
      simultaneously to the mRNA poly(A) tail and eukaryotic translation initiation
      factor 4G (eIF4G). PABP activity is regulated by PABP-interacting (Paip)
      proteins. Paip1 binds PABP and stimulates translation by an unknown mechanism.
      Here, we describe the interaction between Paip1 and eIF3, which is direct, RNA
      independent, and mediated via the eIF3g (p44) subunit. Stimulation of translation
      by Paip1 in vivo was decreased upon deletion of the N-terminal sequence
      containing the eIF3-binding domain and upon silencing of PABP or several eIF3
      subunits. We also show the formation of ternary complexes composed of Paip1-PABP
      eIF4G and Paip1-eIF3-eIF4G. Taken together, these data demonstrate that the eIF3
      Paip1 interaction promotes translation. We propose that eIF3-Paip1 stabilizes the
      interaction between PABP and eIF4G, which brings about the circularization of the
      mRNA.

PMID- 18725401
TI  - Embryonic stem cell-specific miR302-367 cluster: human gene structure and
      functional characterization of its core promoter.
AB  - MicroRNAs (miRNAs) play a central role in the regulation of multiple biological
      processes including the maintenance of stem cell self-renewal and pluripotency.
      Recently, the miRNA cluster miR302-367 was shown to be differentially expressed
      in embryonic stem cells (ESCs). Unfortunately, very little is known about the
      genomic structure of miRNA-encoding genes and their transcriptional units. Here,
      we have characterized the structure of the gene coding for the human miR302-367
      cluster. We identify the transcriptional start and functional core promoter
      region which specifically drives the expression of this miRNA cluster. The
      promoter activity depends on the ontogeny and hierarchical cellular stage. It is
      functional during embryonic development, but it is turned off later in
      development. From a hierarchical standpoint, its activity decays upon
      differentiation of ESCs, suggesting that its activity is restricted to the ESC
      compartment and that the ESC-specific expression of the miR302-367 cluster is
      fully conferred by its core promoter transcriptional activity. Furthermore,
      algorithmic prediction of transcription factor binding sites and knockdown
      studies suggest that ESC-associated transcription factors, including Nanog,
      Oct3/4, Sox2, and Rex1 may be upstream regulators of miR302-367 promoter. This
      study represents the first identification, characterization, and functional
      validation of a human miRNA promoter in stem cells. This study opens up new
      avenues to further investigate the upstream transcriptional regulation of the
      miR302-367 cluster and to dissect how these miRNAs integrate in the complex
      molecular network conferring stem cell properties to ESCs.

PMID- 18725403
TI  - Primary care identification of infants at high risk for overweight and obesity.

PMID- 18725404
TI  - Anxiety, fear of cancer, and perceived risk of cancer following lung cancer
      screening.
AB  - BACKGROUND: Lung cancer screening can result in a high rate of indeterminate
      findings and has not yet been proven to be efficacious in reducing mortality. To
      date, the psychological consequences of receiving an indeterminate screening
      result are not known. METHODS: Four hundred individuals were recruited into this
      study. Participants completed 4 surveys: baseline, after lung screening results
      were known, and at 6 and 12 mo after screening. Demographics, state/trait
      anxiety, fear of cancer, and perceived risk of lung cancer were measured. Mixed
      model regressions were used to determine whether the levels and time trends of
      outcome variables were different among individuals with different screening
      outcomes. RESULTS: An indeterminate screening result increased state anxiety of
      participants, although anxiety then decreased over time. The objective risk of
      cancer is lower for individuals with an indeterminate screen than their initial
      perceived risk, and screening did not change their perceived risk of cancer.
      Those with a suspicious screening result had increased perceived risk of cancer
      and fear of cancer after screening, and these effects also diminished over time.
      Individuals with a negative screen had a temporary reduction in perceived risk of
      cancer. CONCLUSIONS: Individuals who are screened for lung cancer and receive an
      indeterminate or suspicious screening result have some negative psychological
      effects from being screened. The results suggest that individuals who are
      considering screening should be fully informed of the risk of negative
      psychosocial consequences and that individuals who have been screened should
      receive clear and detailed information on interpreting screening results.

PMID- 18725402
TI  - The Schizosaccharomyces pombe Pfh1p DNA helicase is essential for the maintenance
      of nuclear and mitochondrial DNA.
AB  - Schizosaccharomyces pombe Pfh1p is an essential member of the Pif family of 5'-3'
      DNA helicases. The two Saccharomyces cerevisiae homologs, Pif1p and Rrm3p,
      function in nuclear DNA replication, telomere length regulation, and
      mitochondrial genome integrity. We demonstrate here the existence of multiple
      Pfh1p isoforms that localized to either nuclei or mitochondria. The catalytic
      activity of Pfh1p was essential in both cellular compartments. The absence of
      nuclear Pfh1p resulted in G(2) arrest and accumulation of DNA damage foci, a
      finding suggestive of an essential role in DNA replication. Exogenous DNA damage
      resulted in localization of Pfh1p to DNA damage foci, suggesting that nuclear
      Pfh1p also functions in DNA repair. The absence of mitochondrial Pfh1p caused
      rapid depletion of mitochondrial DNA. Despite localization to nuclei and
      mitochondria in S. pombe, neither of the S. cerevisiae homologs, nor human PIF1,
      suppressed the lethality of pfh1Delta cells. However, the essential nuclear
      function of Pfh1p could be supplied by Rrm3p. Expression of Rrm3p suppressed the
      accumulation of DNA damage foci but not the hydroxyurea sensitivity of cells
      depleted of nuclear Pfh1p. Together, these data demonstrate that Pfh1p has
      essential roles in the replication of both nuclear and mitochondrial DNA.

PMID- 18725405
TI  - Beyond utilitarianism: a method for analyzing competing ethical principles in a
      decision analysis of liver transplantation.
AB  - BACKGROUND: The utilitarian foundation of decision analysis limits its usefulness
      for many social policy decisions. In this study, the authors examine a method to
      incorporate competing ethical principles in a decision analysis of liver
      transplantation for a patient with acute liver failure (ALF). METHODS: A Markov
      model was constructed to compare the benefit of transplantation for a patient
      with ALF versus the harm caused to other patients on the waiting list and to
      determine the lowest acceptable 5-y posttransplant survival for the ALF patient.
      The weighting of the ALF patient and other patients was then adjusted using a
      multiattribute variable incorporating utilitarianism, urgency, and other
      principles such as fair chances. RESULTS: In the base-case analysis, the strategy
      of transplanting the ALF patient resulted in a 0.8% increase in the risk of death
      and a utility loss of 7.8 quality-adjusted days of life for each of the other
      patients on the waiting list. These harms cumulatively outweighed the benefit of
      transplantation for an ALF patient having a posttransplant survival of less than
      48% at 5 y. However, the threshold for an acceptable posttransplant survival for
      the ALF patient ranged from 25% to 56% at 5 y, depending on the ethical
      principles involved. DISCUSSION: The results of the decision analysis vary
      depending on the ethical perspective. This study demonstrates how competing
      ethical principles can be numerically incorporated in a decision analysis.

PMID- 18725406
TI  - Labor market productivity costs for caregivers of children with spina bifida: a
      population-based analysis.
AB  - BACKGROUND: Caregiver productivity costs are an important component of the
      overall cost of care for individuals with birth defects and developmental
      disabilities, yet few studies provide estimates for use in economic evaluations.
      OBJECTIVE: This study estimates labor market productivity costs for caregivers of
      children and adolescents with spina bifida. METHODS: Case families were recruited
      from a state birth defects registry in Arkansas. Primary caregivers of children
      with spina bifida (N = 98) reported their employment status in the past year and
      demographic characteristics. Controls were abstracted from the Current Population
      Survey covering the state of Arkansas for the same time period (N = 416).
      Estimates from regression analyses of labor market outcomes were used to
      calculate differences in hours worked per week and lifetime costs. RESULTS:
      Caregivers of children with spina bifida worked an annual average of 7.5 to 11.3
      hours less per week depending on the disability severity. Differences in work
      hours by caregivers of children with spina bifida translated into lifetime costs
      of $133,755 in 2002 dollars using a 3% discount rate and an age- and sex-adjusted
      earnings profile. Including caregivers' labor market productivity costs in
      prevention effectiveness estimates raises the net cost savings per averted case
      of spina bifida by 48% over the medical care costs alone. CONCLUSIONS:
      Information on labor market productivity costs for caregivers can be used to
      better inform economic evaluations of prevention and treatment strategies for
      spina bifida. Cost-effectiveness calculations that omit caregiver productivity
      costs substantially overstate the net costs of the intervention and underestimate
      societal value.

PMID- 18725407
TI  - Obtaining utility estimates of the health value of commonly prescribed treatments
      for asthma and depression.
AB  - BACKGROUND: Comparing the costs and health value associated with alternative
      quality improvement efforts is useful. This study employs expert panel
      methodology to elicit numerical estimates based on a 0 to 1 utility scale of the
      health benefit of usual treatment patterns for 2 medical conditions. METHOD: The
      approach includes development of clinical profiles and derivation of treatment
      benefit estimates via the elicitation of utility ratings before and after
      treatment. Clinical profiles specified characteristics of patient groups,
      treatments to be rated, and their combinations. A panel of 13 asthma and
      depression experts made a series of utility ratings (before any new treatment, 1
      or 3 mo later with no treatment, 1 or 3 mo after initiating various common
      treatments) for adult patient groups with depression or asthma. The panel
      convened to discuss discrepancies and subsequently made final ratings. Treatment
      benefit estimates were derived from the ratings made by the panelists after the
      panel meeting. RESULTS: The treatment benefit estimates had face validity and
      minimal variability, indicating considerable consensus among experts. Treatment
      benefit estimates ranged from -0.03 to 0.25 for depression and from -0.04 to 0.24
      for asthma. There was minimal variation in the estimates for both conditions (the
      estimates' standard deviations ranged from 0.01 to 0.06). Comparisons of the
      treatment benefit estimates before and after the expert panel meeting indicated
      substantial convergence, and evidence suggests that the benefit estimates are
      comparable across the 2 health conditions. CONCLUSION: Comparable estimates of
      treatment benefit for distinct health conditions can be obtained from experts
      using the expert panel methodology.

PMID- 18725408
TI  - Characterization of the Ca2+ -regulated ezrin-S100P interaction and its role in
      tumor cell migration.
AB  - Ezrin is a multidomain protein providing regulated membrane-cytoskeleton contacts
      that play a role in cell differentiation, adhesion, and migration. Within the
      cytosol of resting cells ezrin resides in an autoinhibited conformation in which
      the N- and C-terminal ezrin/radixin/moesin (ERM) association domains (ERMADs)
      interact with one another. Activation of the ezrin membrane-cytoskeleton linker
      function requires an opening of this interdomain association that can result from
      phosphatidylinositol 4,5-bisphosphate binding to the N-ERMAD and threonine 567
      phosphorylation in the C-ERMAD. We have shown that ezrin can also be activated by
      Ca(2+)-dependent binding of the EF-hand protein S100P. We now provide a
      quantitative analysis of this interaction and map the respective binding sites to
      the F2 lobe in the ezrin N-ERMAD and a stretch of hydrophobic residues in the C
      terminal extension of S100P. Phospholipid binding assays reveal that S100P and
      phosphatidylinositol 4,5-bisphosphate compete to some extent for at least
      partially overlapping binding sites in N-ERMAD. Using interaction-competent as
      well as interaction-incompetent S100P derivatives and permanently active ezrin
      mutants, we also show that the protein interaction and a resulting activation of
      ezrin promote the transendothelial migration of tumor cells. Thus, a
      prometastatic role of ezrin and S100P that had been proposed based on their
      overexpression in highly metastatic cancers is probably due to a direct
      interaction between the two proteins and the S100P-mediated activation of ezrin.

PMID- 18725409
TI  - Charged amino acid residues 997-1000 of human apolipoprotein B100 are critical
      for the initiation of lipoprotein assembly and the formation of a stable
      lipidated primordial particle in McA-RH7777 cells.
AB  - We previously demonstrated that a portion, or perhaps all, of the residues
      between 931 and 1000 of apolipoprotein (apo) B100 are required for the initiation
      of apoB-containing particle assembly. Based on our structural model of the first
      1000 residues of apoB (designated as apoB:1000), we hypothesized that this domain
      folds into a three-sided lipovitellin-like "lipid pocket" via a hairpin-bridge
      mechanism. We proposed that salt bridges are formed between four tandem charged
      residues 717-720 in the turn of the hairpin bridge and four tandem complementary
      residues 997-1000 located at the C-terminal end of the model. To identify the
      specific motif within residues 931 and 1000 that is critical for apoB particle
      assembly, apoB:956 and apoB:986 were produced. To test the hairpin-bridge
      hypothesis, the following mutations were made: 1) residues 997-1000 deletion
      (apoB:996), 2) residues 717-720 deletion (apoB:1000Delta717-720), and 3)
      substitution of charged residues 997-1000 with alanines (apoB:996 + 4Ala).
      Characterization of particles secreted by stable transformants of McA-RH7777
      cells demonstrated the following. 1) ApoB:956 did not form stable particles and
      was secreted as large lipid-rich aggregates. 2) ApoB:986 formed both a lipidated
      particle that was denser than HDL(3) and large lipid-rich aggregates. 3) Compared
      with wild-type apoB:1000, apoB:1000Delta717-720 displayed the following: (i)
      significantly diminished capacity to form intact lipidated particles and (ii)
      increased propensity to form large lipid-rich aggregates. 4) In striking contrast
      to wild-type apoB:1000, (i) apoB:996 and apoB:996 + 4Ala were highly susceptible
      to intracellular degradation, (ii) only a small proportion of the secreted
      proteins formed stable HDL(3)-like lipoproteins, and (iii) a majority of the
      secreted proteins formed large lipid-rich aggregates. We conclude that the first
      1000 amino acid residues of human apoB100 are required for the initiation of
      nascent apoB-containing lipoprotein assembly, and residues 717-720 and 997-1000
      play key roles in this process, perhaps via a hairpin-bridge mechanism.

PMID- 18725410
TI  - Activation mechanism of recombinant Der p 3 allergen zymogen: contribution of
      cysteine protease Der p 1 and effect of propeptide glycosylation.
AB  - The trypsin-like protease Der p 3, a major allergen of the house dust mite
      Dermatophagoides pteronyssinus, is synthesized as a zymogen, termed proDer p 3.
      No recombinant source of Der p 3 has been described yet, and the zymogen
      maturation mechanism remains to be elucidated. The Der p 3 zymogen was produced
      in Pichia pastoris. We demonstrated that the recombinant zymogen is glycosylated
      at the level of its propeptide. We showed that the activation mechanism of proDer
      p 3 is intermolecular and is mediated by the house dust mite cysteine protease
      Der p 1. The primary structure of the proDer p 3 propeptide is associated with a
      unique zymogen activation mechanism, which is different from those described for
      the trypsin-like family and relies on the house dust mite papain-like protease
      Der p 1. This is the first report of a recombinant source of Der p 3, with the
      same enzymatic activity as the natural enzyme and trypsin. Glycosylation of the
      propeptide was found to decrease the rate of maturation. Finally, we showed that
      recombinant Der p 3 is inhibited by the free modified prosequence T(P1)R.

PMID- 18725412
TI  - Proline-directed pseudo-phosphorylation at AT8 and PHF1 epitopes induces a
      compaction of the paperclip folding of Tau and generates a pathological (MC-1)
      conformation.
AB  - Tau, a neuronal microtubule-associated protein that aggregates in Alzheimer
      disease is a natively unfolded protein. In solution, Tau adopts a "paperclip"
      conformation, whereby the N- and C-terminal domains approach each other and the
      repeat domain ( Jeganathan, S., von Bergen, M., Brutlach, H., Steinhoff, H. J.,
      and Mandelkow, E. (2006) Biochemistry 45, 2283-2293 ). In AD, Tau is in a
      hyperphosphorylated state. The consequences for microtubule binding or
      aggregation are a matter of debate. We therefore tested whether phosphorylation
      alters the conformation of Tau. To avoid the ambiguities of heterogeneous
      phosphorylation we cloned "pseudo-phosphorylation" mutants of Tau where
      combinations of Ser or Thr residues were converted into Glu. These mutations were
      combined with FRET pairs inserted in different locations to allow distance
      measurements. The results show that the paperclip conformation becomes tighter or
      looser, depending on the pseudo-phosphorylation state. In particular, pseudo
      phosphorylation at the epitope of the diagnostic antibody AT8* (S199E + S202E +
      T205E) moves the N-terminal domain away from the C-terminal domain. Pseudo
      phosphorylation at the PHF1 epitope (S396E + S404E) moves the C-terminal domain
      away from the repeat domain. In both cases the paperclip conformation is opened
      up. By contrast, the combination of AT8* and PHF1 sites leads to compaction of
      the paperclip, such that the N-terminus approaches the repeat domain. The
      compaction becomes even stronger by combining pseudo-phosphorylated AT8*, AT100,
      and PHF1 epitopes. This is accompanied by a strong increase in the reaction with
      conformation-dependent antibody MC1, suggesting the generation of a pathological
      conformation characteristic for Tau in AD. Furthermore, the compact paperclip
      conformation enhances the aggregation to paired helical filaments but has little
      influence on microtubule interactions. The data provide a framework for the
      global folding of Tau dependent on proline-directed phosphorylation in the
      domains flanking the repeats and the consequences for pathological properties of
      Tau.

PMID- 18725411
TI  - Functional adhesiveness of the CX3CL1 chemokine requires its aggregation. Role of
      the transmembrane domain.
AB  - In its native form, the chemokine CX3CL1 is a firmly adhesive molecule promoting
      leukocyte adhesion and migration and hence involved, along with its unique
      receptor CX3CR1, in various inflammatory processes. Here we investigated the role
      of molecular aggregation in the CX3CL1 adhesiveness. Assays of bioluminescence
      resonance energy transfer (BRET) and homogeneous time-resolved fluorescence
      (HTRF) in transfected cell lines and in primary cells showed specific signals
      indicative of CX3CL1 clustering. Truncation experiments showed that the
      transmembrane domain played a central role in this aggregation. A chimera with
      mutations of the 12 central transmembrane domain residues had significantly
      reduced BRET signals and characteristics of a non-clustering molecule. This
      mutant was weakly adhesive according to flow and dual pipette adhesion assays and
      was less glycosylated than CX3CL1, although, as we demonstrated, loss of
      glycosylation did not affect the CX3CL1 adhesive potency. We postulate that cell
      surfaces express CX3CL1 as a constitutive oligomer and that this oligomerization
      is essential for its adhesive potency. Inhibition of CX3CL1 self-assembly could
      limit the recruitment of CX3CR1-positive cells and may be a new pathway for anti
      inflammatory therapies.

PMID- 18725413
TI  - The diversity of O-linked glycans expressed during Drosophila melanogaster
      development reflects stage- and tissue-specific requirements for cell signaling.
AB  - Appropriate glycoprotein O-glycosylation is essential for normal development and
      tissue function in multicellular organisms. To comprehensively assess the
      developmental and functional impact of altered O-glycosylation, we have
      extensively analyzed the non-glycosaminoglycan, O-linked glycans expressed in
      Drosophila embryos. Through multidimensional mass spectrometric analysis of
      glycans released from glycoproteins by beta-elimination, we detected novel as
      well as previously reported O-glycans that exhibit developmentally modulated
      expression. The core 1 mucin-type disaccharide (Galbeta1-3GalNAc) is the
      predominant glycan in the total profile. HexNAcitol, hexitol, xylosylated
      hexitol, and branching extension of core 1 with HexNAc (to generate core 2
      glycans) were also evident following release and reduction. After Galbeta1
      3GalNAc, the next most prevalent glycans were a mixture of novel, isobaric,
      linear, and branched forms of a glucuronyl core 1 disaccharide. Other less
      prevalent structures were also extended with HexA, including an O-fucose glycan.
      Although the expected disaccharide product of the Fringe glycosyltransferase,
      (GlcNAcbeta1-3)fucitol, was not detectable in whole embryos, mass spectrometry
      fragmentation and exoglycosidase sensitivity defined a novel glucuronyl
      trisaccharide as GlcNAcbeta1-3(GlcAbeta1-4)fucitol. Consistent with the spatial
      distribution of the Fringe function, the GlcA-extended form of the Fringe product
      was enriched in the dorsal portion of the wing imaginal disc. Furthermore, loss
      of Fringe activity reduced the prevalence of the O-Fuc trisaccharide. Therefore,
      O-Fuc glycans necessary for the modulation of important signaling events in
      Drosophila are, as in vertebrates, substrates for extension beyond the addition
      of a single HexNAc.

PMID- 18725414
TI  - Irreversible oxidation of the active-site cysteine of peroxiredoxin to cysteine
      sulfonic acid for enhanced molecular chaperone activity.
AB  - The thiol (-SH) of the active cysteine residue in peroxiredoxin (Prx) is known to
      be reversibly hyperoxidized to cysteine sulfinic acid (-SO(2)H), which can be
      reduced back to thiol by sulfiredoxin/sestrin. However, hyperoxidized Prx of an
      irreversible nature has not been reported yet. Using an antibody developed
      against the sulfonylated (-SO(3)H) yeast Prx (Tsa1p) active-site peptide
      (AFTFVCPTEI), we observed an increase in the immunoblot intensity in proportion
      to the H(2)O(2) concentrations administered to the yeast cells. We identified two
      species of hyperoxidized Tsa1p: one can be reduced back (reversible) with
      sulfiredoxin, and the other cannot (irreversible). Irreversibly hyperoxidized
      Tsa1p was identified as containing the active-site cysteine sulfonic acid (Tsa1p
      SO(3)H) by mass spectrometry. Tsa1p-SO(3)H was not an autoxidation product of
      Tsa1p-SO(2)H and was maintained in yeast cells even after two doubling cycles.
      Tsa1p-SO(3)H self-assembled into a ring-shaped multimeric form was shown by
      electron microscopy. Although the Tsa1p-SO(3)H multimer lost its peroxidase
      activity, it gained approximately 4-fold higher chaperone activity compared with
      Tsa1p-SH. In this study, we identify an irreversibly hyperoxidized Prx, Tsa1p
      SO(3)H, with enhanced molecular chaperone activity and suggest that Tsa1p-SO(3)H
      is a marker of cumulative oxidative stress in cells.

PMID- 18725415
TI  - Protein-tyrosine phosphatase alpha regulates stem cell factor-dependent c-Kit
      activation and migration of mast cells.
AB  - The role of protein-tyrosine phosphatase alpha (PTPalpha) in mast cell function
      was investigated in tissues and cells from PTPalpha-deficient mice. Bone marrow
      derived mast cells (BMMCs) lacking PTPalpha exhibit defective stem cell factor
      (SCF)-dependent polarization and migration. Investigation of the molecular basis
      for this reveals that SCF/c-Kit-stimulated activation of the Fyn tyrosine kinase
      is impaired in PTPalpha(-/-) BMMCs, with a consequent inhibition of site-specific
      c-Kit phosphorylation at tyrosines 567/569 and 719. Although c-Kit-mediated
      activation of phosphatidylinositol 3-kinase and Akt is unaffected, profound
      defects occur in the activation of downstream signaling proteins, including
      mitogen-activated protein kinases and Rho GTPases. Phosphorylation and
      interaction of Fyn effectors Gab2 and Shp2, which are linked to Rac/JNK
      activation in mast cells, are impaired in PTPalpha(-/-) BMMCs. Thus, PTPalpha is
      required for SCF-induced c-Kit and Fyn activation, and in this way regulates a
      Fyn-based c-Kit signaling axis (Fyn/Gab2/Shp2/Vav/PAK/Rac/JNK) that mediates mast
      cell migration. These defective signaling events may underlie the altered tissue
      resident mast cell populations found in PTPalpha(-/-) mice.

PMID- 18725416
TI  - Molecular basis of the Bohr effect in arthropod hemocyanin.
AB  - Flash photolysis and K-edge x-ray absorption spectroscopy (XAS) were used to
      investigate the functional and structural effects of pH on the oxygen affinity of
      three homologous arthropod hemocyanins (Hcs). Flash photolysis measurements
      showed that the well-characterized pH dependence of oxygen affinity (Bohr effect)
      is attributable to changes in the oxygen binding rate constant, k(on), rather
      than changes in k(off). In parallel, coordination geometry of copper in Hc was
      evaluated as a function of pH by XAS. It was found that the geometry of copper in
      the oxygenated protein is unchanged at all pH values investigated, while
      significant changes were observed for the deoxygenated protein as a function of
      pH. The interpretation of these changes was based on previously described
      correlations between spectral lineshape and coordination geometry obtained for
      model compounds of known structure (Blackburn, N. J., Strange, R. W., Reedijk,
      J., Volbeda, A., Farooq, A., Karlin, K. D., and Zubieta, J. (1989) Inorg. Chem.,
      28, 1349-1357). A pH-dependent change in the geometry of cuprous copper in the
      active site of deoxyHc, from pseudotetrahedral toward trigonal was assigned from
      the observed intensity dependence of the 1s --> 4p(z) transition in x-ray
      absorption near edge structure (XANES) spectra. The structural alteration
      correlated well with increase in oxygen affinity at alkaline pH determined in
      flash photolysis experiments. These results suggest that the oxygen binding rate
      in deoxyHc depends on the coordination geometry of Cu(I) and suggest a structural
      origin for the Bohr effect in arthropod Hcs.

PMID- 18725417
TI  - Delta protein kinase C interacts with the d subunit of the F1F0 ATPase in
      neonatal cardiac myocytes exposed to hypoxia or phorbol ester. Implications for
      F1F0 ATPase regulation.
AB  - Mitochondrial protein kinase C isozymes have been reported to mediate both
      cardiac ischemic preconditioning and ischemia/reperfusion injury. In addition,
      cardiac preconditioning improves the recovery of ATP levels after
      ischemia/reperfusion injury. We have, therefore, evaluated protein kinase C
      modulation of the F(1)F(0) ATPase in neonatal cardiac myocytes. Exposure of cells
      to 3 or 100 nM 4beta-phorbol 12-myristate-13-acetate induced co
      immunoprecipitation of delta protein kinase C (but not alpha, epsilon, or zeta
      protein kinase C) with the d subunit of the F(1)F(0) ATPase. This co
      immunoprecipitation correlated with 40+/-3% and 72+/-9% inhibitions of oligomycin
      sensitive F(1)F(0) ATPase activity, respectively. We observed prominent
      expression of delta protein kinase C in cardiac myocyte mitochondria, which was
      enhanced following a 4-h hypoxia exposure. In contrast, hypoxia decreased
      mitochondrial zetaPKC levels by 85+/-1%. Following 4 h of hypoxia, F(1)F(0)
      ATPase activity was inhibited by 75+/-9% and delta protein kinase C co
      immunoprecipitated with the d subunit of F(1)F(0) ATPase. In vitro incubation of
      protein kinase C with F(1)F(0) ATPase enhanced F(1)F(0) activity in the absence
      of protein kinase C activators and inhibited it in the presence of activators.
      Recombinant delta protein kinase C also inhibited F(1)F(0) ATPase activity.
      Protein kinase C overlay assays revealed delta protein kinase C binding to the d
      subunit of F(1)F(0) ATPase, which was modulated by diacylglycerol,
      phosphatidylserine, and cardiolipin. Our results suggest a novel regulation of
      the F(1)F(0) ATPase by the delta protein kinase C isozyme.

PMID- 18725418
TI  - A Replication-Limited Recombinant Mycobacterium bovis BCG vaccine against
      tuberculosis designed for human immunodeficiency virus-positive persons is safer
      and more efficacious than BCG.
AB  - Tuberculosis is the leading cause of death in AIDS patients, yet the current
      tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG), is
      contraindicated for immunocompromised individuals, including human
      immunodeficiency virus-positive persons, because it can cause disseminated
      disease; moreover, its efficacy is suboptimal. To address these problems, we have
      engineered BCG mutants that grow normally in vitro in the presence of a
      supplement, are preloadable with supplement to allow limited growth in vivo, and
      express the highly immunoprotective Mycobacterium tuberculosis 30-kDa major
      secretory protein. The limited replication in vivo renders these vaccines safer
      than BCG in SCID mice yet is sufficient to induce potent cell-mediated and
      protective immunity in the outbred guinea pig model of pulmonary tuberculosis. In
      the case of one vaccine, rBCG(mbtB)30, protection was superior to that with BCG
      (0.3-log fewer CFU of M. tuberculosis in the lung [P < 0.04] and 0.6-log fewer
      CFU in the spleen [P = 0.001] in aerosol-challenged animals [means for three
      experiments]); hence, rBCG(mbtB)30 is the first live mycobacterial vaccine that
      is both more attenuated than BCG in the SCID mouse and more potent than BCG in
      the guinea pig. Our study demonstrates the feasibility of developing safer and
      more potent vaccines against tuberculosis. The novel approach of engineering a
      replication-limited vaccine expressing a recombinant immunoprotective antigen and
      preloading it with a required nutrient, such as iron, that is capable of being
      stored should be generally applicable to other live vaccine vectors targeting
      intracellular pathogens.

PMID- 18725419
TI  - Role of NleH, a type III secreted effector from attaching and effacing pathogens,
      in colonization of the bovine, ovine, and murine gut.
AB  - The human pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 colonizes
      human and animal gut via formation of attaching and effacing lesions. EHEC
      strains use a type III secretion system to translocate a battery of effector
      proteins into the mammalian host cell, which subvert diverse signal transduction
      pathways implicated in actin dynamics, phagocytosis, and innate immunity. The
      genomes of sequenced EHEC O157:H7 strains contain two copies of the effector
      protein gene nleH, which share 49% sequence similarity with the gene for the
      Shigella effector OspG, recently implicated in inhibition of migration of the
      transcriptional regulator NF-kappaB to the nucleus. In this study we investigated
      the role of NleH during EHEC O157:H7 infection of calves and lambs. We found that
      while EHEC DeltanleH colonized the bovine gut more efficiently than the wild-type
      strain, in lambs the wild-type strain exhibited a competitive advantage over the
      mutant during mixed infection. Using the mouse pathogen Citrobacter rodentium,
      which shares many virulence factors with EHEC O157:H7, including NleH, we
      observed that the wild-type strain exhibited a competitive advantage over the
      mutant during mixed infection. We found no measurable differences in T-cell
      infiltration or hyperplasia in colons of mice inoculated with the wild-type or
      the nleH mutant strain. Using NF-kappaB reporter mice carrying a transgene
      containing a luciferase reporter driven by three NF-kappaB response elements, we
      found that NleH causes an increase in NF-kappaB activity in the colonic mucosa.
      Consistent with this, we found that the nleH mutant triggered a significantly
      lower tumor necrosis factor alpha response than the wild-type strain.

PMID- 18725420
TI  - ZapA, a virulence factor in a rat model of Proteus mirabilis-induced acute and
      chronic prostatitis.
AB  - Our knowledge of pathogenesis has benefited from a better understanding of the
      roles of specific virulence factors in disease. To determine the role of the
      virulence factor ZapA, a 54-kDa metalloproteinase of Proteus mirabilis, in
      prostatitis, rats were infected with either wild-type (WT) P. mirabilis or its
      isogenic ZapA(-) mutant KW360. The WT produced both acute and chronic prostatitis
      showing the typical histological progressions that are the hallmarks of these
      diseases. Infection with the ZapA(-) mutant, however, resulted in reduced levels
      of acute prostatitis, as determined from lower levels of tissue damage, bacterial
      colonization, and inflammation. Further, the ZapA(-) mutant failed to establish a
      chronic infection, in that bacteria were cleared from the prostate, inflammation
      was resolved, and tissue was seen to be healing. Clearance from the prostate was
      not the result of a reduced capacity of the ZapA(-) mutant to form biofilms in
      vitro. These finding clearly define ZapA as an important virulence factor in both
      acute and chronic bacterial prostatitis.

PMID- 18725421
TI  - Escherichia coli O157:H7 survives within human macrophages: global gene
      expression profile and involvement of the Shiga toxins.
AB  - Escherichia coli O157:H7 is an important food-borne pathogen that specifically
      binds to the follicle-associated epithelium in the intestine, which rapidly
      brings this bacterial pathogen in contact with underlying human macrophages. Very
      little information is available about the interaction between E. coli O157:H7 and
      human macrophages. We evaluated the uptake and survival of strain EDL933 during
      infection of human macrophages. Surprisingly, EDL933 survived and multiplied in
      human macrophages at 24 h postinfection. The global gene expression profile of
      this pathogen during macrophage infection was determined. Inside human
      macrophages, upregulation of E. coli O157:H7 genes carried on O islands (such as
      pagC, the genes for both of the Shiga toxins, and the two iron transport system
      operons fit and chu) was observed. Genes involved in acid resistance and in the
      SOS response were upregulated. However, genes of the locus of enterocyte
      effacement or genes involved in peroxide resistance were not differentially
      expressed. Many genes with putative or unknown functions were upregulated inside
      human macrophages and may be newly discovered virulence factors. As the Shiga
      toxin genes were upregulated in macrophages, survival and cytotoxicity assays
      were performed with isogenic Shiga toxin mutants. The initial uptake of Shiga
      toxins mutants was higher than that of the wild type; however, the survival rates
      were significantly lower at 24 h postinfection. Thus, Shiga toxins are implicated
      in the interaction between E. coli O157:H7 and human macrophages. Understanding
      the molecular mechanisms used by E. coli to survive within macrophages may help
      in the identification of targets for new therapeutic agents.

PMID- 18725422
TI  - The interaction of Streptococcus pneumoniae with plasmin mediates transmigration
      across endothelial and epithelial monolayers by intercellular junction cleavage.
AB  - The precise mechanisms by which Streptococcus pneumoniae overcomes epithelial and
      endothelial barriers to access underlying human tissues remain to be determined.
      The plasminogen system is highly important for the tissue barrier degradation
      which allows cell migration. Plasminogen is known to interact with pneumococci
      via enolase, glyceraldehyde-3-phosphate dehydrogenase, and choline-binding
      protein E. These observations prompted us to evaluate the role of this
      proteolytic system in the pneumococcal invasion process. We observed that coating
      of S. pneumoniae R6 strain with plasminogen or inactivated plasmin increased
      adherence to pulmonary epithelial A549 and vascular endothelial EaHy cells in
      vitro. This indicates that plasminogen-mediated adherence is independent of the
      protease activity and involves plasminogen binding to receptors on eukaryotic
      cell surfaces. Conversely, decreased adherence of bacterial cells coated with
      active plasmin was observed, indicating that the protease activity limits
      bacterial attachment on the cell surface. We were then interested in
      investigating the role of the proteolytic plasmin activity in the traversal of
      tissue barriers. We observed that adherence of plasmin-coated D39 (encapsulated)
      or R6 (unencapsulated) pneumococci induced sporadic disruptions of EaHy and A549
      monolayer cell junctions. This was not observed when plasmin was inhibited by
      aprotinin. Endothelial junction disorganization may proceed by proteolysis of the
      cell junction components. This is supported by our observation of the in vitro
      cleavage by plasmin bound to pneumococci of recombinant vascular endothelial
      cadherin, the main component of endothelial adherens junctions. Finally, junction
      damage induced by plasmin may be related to tissue barrier traversal, as we
      measured an increase of S. pneumoniae transmigration across epithelial A549 and
      endothelial EaHy layers when active plasmin was present on the bacterial surface.
      Our results highlight a novel function for the plasminogen recruitment at the
      bacterial surface in facilitating adherence of pneumococci to endothelial and
      epithelial cells, while active plasmin degrades intercellular junctions. This
      process promotes migration of pneumococci through cell barriers by a pericellular
      route, a prerequisite for dissemination of S. pneumoniae in the host organism.

PMID- 18725424
TI  - The roles of physiological and subjective stress in the effectiveness of a
      placebo on experimentally induced pain.
AB  - OBJECTIVE: To examine whether reduction of negative emotions and associated
      autonomic activity could explain placebo analgesia, and to test the effect of
      experimenter gender on the placebo analgesic response. METHODS: Sixty-three (n =
      32 females) students participated in a within-subjects design where subjects were
      tested on two separate days, one day for the experimental condition (placebo) and
      one day for the natural history condition. In the experimental condition, the
      participants received capsules containing lactose with information that the
      capsules were a high dose of a potent painkiller. In the natural history
      condition, the procedures were identical except that the placebo capsules were
      not administrated. The experimenters were blinded to the fact that all
      participants received placebo. Pain was induced by a thermode holding +46 degrees
      C with duration of 240 seconds to the forearm. Electrocardiogram was measured to
      obtain data for analysis of heart rate variability. Subjective measurements
      consisted of pain intensity, pain unpleasantness, stress, arousal, and mood.
      RESULTS: The results showed a placebo effect on pain intensity and a concomitant
      reduction in subjective stress and cardiac activity. Stepwise regressions
      revealed that reduced subjective stress was the only predictor for the placebo
      analgesic response. Contrary to our hypothesis, male subjects displayed increased
      placebo analgesia when a male acted as experimenter. CONCLUSIONS: The results
      indicate that reduced negative emotional activation could be a mechanism in
      placebo analgesia and that experimenter gender is probably not systematically
      related to placebo analgesia.

PMID- 18725423
TI  - Temporal delay of peak T-cell immunity determines Chlamydia pneumoniae pulmonary
      disease in mice.
AB  - Severe chlamydial disease typically occurs after previous infections and results
      from a hypersensitivity response that is also required for chlamydial
      elimination. Here, we quantitatively dissected the immune and disease responses
      to repeated Chlamydia pneumoniae lung infection by multivariate modeling with
      four dichotomous effects: mouse strain (A/J or C57BL/6), dietary protein content
      (14% protein and 0.3% L-cysteine-0.9% L-arginine, or 24% protein and 0.5% L
      cysteine-2.0% L-arginine), dietary antioxidant content (90 IU alpha-tocopherol/kg
      body weight versus 450 IU alpha-tocopherol/kg and 0.1% g L-ascorbate), and time
      course (3 or 10 days postinfection). Following intranasal C. pneumoniae
      challenge, C57BL/6 mice on a low-protein/low-antioxidant diet, but not C57BL/6
      mice on other diets or A/J mice, exhibited profoundly suppressed early lung
      inflammatory and pan-T-cell (CD3delta(+)) and helper T-cell (CD45) responses on
      day 3 but later strongly exacerbated disease on day 10. Contrast analyses
      characterized severe C. pneumoniae disease as being a delayed-type
      hypersensitivity (DTH) response with increased lung macrophage and Th1 cell
      marker transcripts, increased Th1:Th2 ratios, and Th1 cytokine-driven
      inflammation. Results from functional analyses by DTH, enzyme-linked immunospot,
      and immunohistofluorescence assays were consistent with the results obtained by
      transcript analysis. Thus, chlamydial disease after secondary infection is a
      temporal dysregulation of the T-cell response characterized by a profoundly
      delayed T-helper cell response that results in a failure to eliminate the
      pathogen and provokes later pathological Th1 inflammation. This delayed T-cell
      response is under host genetic control and nutritional influence. The mechanism
      that temporally and quantitatively regulates the host T-cell population is the
      critical determinant in chlamydial pathogenesis.

PMID- 18725425
TI  - Positive psychological well-being and mortality: a quantitative review of
      prospective observational studies.
AB  - OBJECTIVE: To review systematically prospective, observational, cohort studies of
      the association between positive well-being and mortality using meta-analytic
      methods. Recent years have witnessed increased interest in the relationship
      between positive psychological well-being and physical health. METHODS: We
      searched general bibliographic databases: Medline, PsycINFO, Web of Science, and
      PubMed up to January 2008. Two reviewers independently extracted data on study
      characteristics, quality, and estimates of associations. RESULTS: There were 35
      studies (26 articles) investigating mortality in initially healthy populations
      and 35 studies (28 articles) of disease populations. The meta-analyses showed
      that positive psychological well-being was associated with reduced mortality in
      both the healthy population (combined hazard ratio (HR) = 0.82; 95% Confidence
      Interval (CI) = 0.76-0.89; p < .001) and the disease population (combined HR =
      0.98; CI = 0.95-1.00; p = .030) studies. There were indications of publication
      bias in this literature, although the fail-safe numbers were 2444 and 1397 for
      healthy and disease population studies, respectively. Intriguingly, meta-analysis
      of studies that controlled for negative affect showed that the protective effects
      of positive psychological well-being were independent of negative affect. Both
      positive affect (e.g., emotional well-being, positive mood, joy, happiness,
      vigor, energy) and positive trait-like dispositions (e.g., life satisfaction,
      hopefulness, optimism, sense of humor) were associated with reduced mortality in
      healthy population studies. Positive psychological well-being was significantly
      associated with reduced cardiovascular mortality in healthy population studies,
      and with reduced death rates in patients with renal failure and with human
      immunodeficiency virus-infection. CONCLUSIONS: The current review suggests that
      positive psychological well-being has a favorable effect on survival in both
      healthy and diseased populations.

PMID- 18725426
TI  - Physical and mental comorbidity of headache in a nationally representative sample
      of US adults.
AB  - OBJECTIVE: To investigate the contribution of comorbidity to health utilization
      and negative health perception in a large-scale population-based study.
      Comorbidity of headache with physical and mental disorders has been reported
      frequently in clinical samples. METHODS: This concern was addressed using
      combined 6-year data from the 1999 to 2004 National Health Examination and
      Nutrition Survey (n = 31,126 adults), nationally representative datasets of the
      US population. Measures of physical disorders were based on standardized
      interviews of chronic conditions, and mental disorders were assessed by the
      Composite International Diagnostic Interview for Diagnostic and Statistical
      Manual of Mental Disorders, 4th Edition. RESULTS: The 3-month prevalence of
      severe headaches or migraine in the US general population was 22.73%, with
      females and young adults having greater rates than males and older adults. Adults
      with headache had increased odds for a variety of physical disorders (including
      asthma, rheumatoid arthritis, and stroke) and mental disorders (including
      depression, generalized anxiety disorder, and panic disorder). Adults with
      headache were more likely to rate their health as "fair or poor" (17.9% versus
      6.1%), to seek health care four or more times in a year (43.3% versus 22.7%), and
      to endorse physical and mental limitations. Health utilization and negative
      health perception were more strongly influenced by comorbid mental disorders than
      physical disorders. CONCLUSIONS: The results from this nationally representative
      sample provide new information on the interrelationships of headache with mental
      and physical disorders. The greater impact of comorbid mental compared with
      physical disorders on healthcare utilization and health perception has important
      implications for the clinical evaluation and treatment of headache in the
      population.

PMID- 18725427
TI  - Glycemic instability and spontaneous energy intake: association with knowledge
      based work.
AB  - OBJECTIVE: To further document the impact of knowledge-based work (KBW) on
      spontaneous energy intake and glucose homeostasis. METHODS: We used a within
      subjects experimental design, in which each participant was engaged in each of
      the three 45-minute conditions followed by an ad libitum buffet, 1) resting in a
      sitting position; 2) reading a document and writing a summary; or 3) performing a
      battery of computerized tests. Fourteen female students (mean age: 22.8 +/- 2.3
      years, mean body mass index: 22.4 +/- 2.5 kg/m(2)) were recruited to participate.
      Plasma glucose, insulin, and cortisol levels at seven time-points, and appetite
      sensation markers were measured at each experimental condition. RESULTS: The mean
      ad libitum energy intake after the reading-writing and the automated test-battery
      conditions exceeded that measured after rest by 848 kJ and 1057 kJ, respectively
      (p < .05). No specific dietary preference was detected, as reflected by the
      comparable percent of energy from each macronutrient in the three conditions. No
      significant difference in appetite sensation markers was observed among the three
      conditions. Mean cortisol level over 45 minutes in the two KBW conditions was
      significantly higher (p < .05) compared with the control condition. Finally, a
      significant increase in variations in plasma glucose and insulin levels was
      observed as compared with the control condition (p < .01). CONCLUSIONS: This
      study showed that KBW acutely induces an increase in spontaneous energy intake,
      and promotes an increased fluctuation in plasma glucose and insulin levels. This
      study contributes to the documentation of a new risk factor for a positive energy
      balance, with the potential to lead to overweight in the long-term.

PMID- 18725428
TI  - Major depression, C-reactive protein, and incident ischemic heart disease in
      healthy men and women.
AB  - OBJECTIVE: To investigate how C-reactive protein (CRP) and major depressive
      disorder (MDD) relate to each other and to incident ischemic heart disease (IHD).
      Studies have shown that both depression and raised CRP concentration predict IHD
      and that elevated CRP is linked with increased risk of depression. METHODS: A
      prospective case-control study of healthy men and women, aged 45 to 79 years, was
      undertaken within the United Kingdom European Prospective Investigation into
      Cancer (EPIC)-Norfolk study. CRP concentration was measured for 726 (fatal or
      nonfatal) IHD cases and 1688 matched controls who completed a baseline MDD self
      assessment, defined by restricted Diagnostic and Statistical Manual of Mental
      Disorders, 4th Edition diagnostic criteria. RESULTS: Past-year MDD was associated
      with increased CRP concentration levels (4.31 mg/L for participants who reported
      episodes of MDD in the past year versus 3.65 mg/L for those who did not; p =
      .003), and the odds ratio for incident IHD associated with higher CRP
      concentration was 2.02 (comparing the top versus bottom quartile of CRP; 95%
      Confidence Interval (CI) = 1.52-2.68), adjusted for cigarette smoking, diabetes,
      systolic blood pressure, body mass index, and cholesterol. The association
      between past-year MDD and IHD was independent of CRP (odds ratio = 1.55; 95% CI =
      1.01-2.37, with adjustments as above, and additionally for CRP). CONCLUSIONS:
      Evidence from this study is supportive of an association between MDD and CRP
      although it suggests that CRP does not account for the association between MDD
      and future IHD.

PMID- 18725429
TI  - Trait anger management style moderates effects of actual ("state") anger
      regulation on symptom-specific reactivity and recovery among chronic low back
      pain patients.
AB  - OBJECTIVES: We examined whether "state" anger regulation-inhibition or expression
      among chronic low back pain (CLBP) patients would affect lower paraspinal (LP)
      muscle tension following anger-induction, and whether these effects were
      moderated by trait anger management style. METHOD: Eighty-four CLBP patients
      underwent harassment, then they regulated anger under one of two conditions: half
      expressed anger by telling stories about people depicted in pictures, whereas
      half inhibited anger by only describing objects appearing in the same pictures.
      They completed the anger-out and anger-in subscales (AOS; AIS) of the anger
      expression inventory. RESULTS: General Linear Model procedures were used to test
      anger regulation condition by AOS/AIS by period interactions for physiological
      indexes. Significant three-way interactions were found such that: a) high trait
      anger-out patients in the inhibition condition appeared to show the greatest LP
      reactivity during the inhibition period followed by the slowest recovery; b) high
      trait anger-out patients in the expression condition appeared to show the
      greatest systolic blood pressure (SBP) reactivity during the expression period
      followed by rapid recovery. CONCLUSIONS: Results implicate LP muscle tension as a
      potential physiological mechanism that links the actual inhibition of anger
      following provocation to chronic pain severity among CLBP patients. Results also
      highlight the importance of mismatch situations for patients who typically
      regulate anger by expressing it. These CLBP patients may be at particular risk
      for elevated pain severity if circumstances at work or home regularly dictate
      that they should inhibit anger expression.

PMID- 18725431
TI  - Persistence of posttraumatic stress symptoms 12 and 36 months after acute
      coronary syndrome.
AB  - OBJECTIVES: To assess the prevalence and predictors of posttraumatic stress
      symptoms in patients at 12 and 36 months post hospital admission for an acute
      coronary syndrome (ACS). There is increasing recognition that posttraumatic
      stress may develop in the aftermath of an acute cardiac event. However, there has
      been little research on the longer-term prevalence of posttraumatic stress
      disorder (PTSD). METHODS: Posttraumatic stress symptoms were assessed at 12
      months in 213 patients with ACS and in 179 patients at 36 months. Predictor
      variables included clinical, demographic, and emotional factors measured during
      hospital admission. RESULTS: At 12 months post ACS, 26 (12.2%) patients qualified
      for a diagnosis of PTSD; 23 (12.8%) patients were identified with PTSD at 36
      months. Posttraumatic symptoms at 12 months were associated with younger age,
      ethnic minority status, social deprivation, cardiac symptom recurrence, history
      of depression, depressed mood during admission, hostility, and Type D
      personality. In multiple regression, depressed mood during admission and
      recurrent cardiac symptoms were independent predictors of posttraumatic symptoms
      (R(2) = 0.507, p < .001). At 36 months, posttraumatic stress symptoms were
      independently predicted by posttraumatic symptom levels at 12 months and
      depressed mood during admission (R(2) = 0.635, p < .001). CONCLUSION:
      Posttraumatic stress symptoms persist for at least 3 years after an acute cardiac
      event. Early emotional responses are important in predicting longer-term
      posttraumatic stress. It is important to identify patients at risk for
      posttraumatic stress as they are more likely to experience reduced quality of
      life.

PMID- 18725430
TI  - Nighttime heart rate and survival in depressed patients post acute myocardial
      infarction.
AB  - OBJECTIVES: To determine if: 1) depressed patients with a recent acute myocardial
      infarction (AMI) have higher nighttime heart rate (HR) than nondepressed
      patients, and 2) elevated nighttime HR is associated with decreased survival post
      AMI. Depression is a risk factor for mortality post AMI. It is also associated
      with sleep disturbances and with elevated HR, which may be more pronounced at
      night. Resting and 24-hour HR have been found to predict mortality in patient and
      community samples. METHODS: Ambulatory electrocardiographic data were obtained
      from 333 depressed patients and 383 nondepressed patients with recent AMI. They
      were followed for up to 30 months (median = 24 months). RESULTS: Depressed
      patients had higher nighttime HR (70.7 +/- 0.7 versus 67.7 +/- 0.6 beats per
      minute (bpm); p = .001), and daytime HR (76.4 +/- 0.7 versus 74.2 +/- 0.6 bpm; p
      = .02) than nondepressed patients, even after adjusting for potential confounds.
      Depression (hazard ratio (Haz R) = 2.19; p = .02) and nighttime HR (Haz R = 1.03;
      p = .004), but not daytime HR, predicted survival after adjusting for other major
      predictors and for each other. The interaction between nighttime HR and
      depression on survival approached, but did not achieve, significance (p = .08).
      CONCLUSIONS: Mean day and nighttime HR values are higher in depressed patients
      than in nondepressed patients post AMI. Depression and elevated nighttime HR, but
      not daytime HR, are independent predictors of survival in these patients.
      Although depressed patients have a higher nighttime HR than nondepressed
      patients, nighttime HR predicts mortality in both depressed and nondepressed
      patients.

PMID- 18725432
TI  - Educational attainment and the heritability of self-reported hypertension among
      male Vietnam-era twins.
AB  - OBJECTIVE: To investigate the potential for gene x environment interaction in
      hypertension by examining the extent to which educational attainment modifies the
      heritability of hypertension in male twins. Prior twin and family studies have
      established that hypertension runs in families and is heritable. In addition,
      epidemiological research indicates that the prevalence of hypertension differs by
      socioeconomic factors, such as educational attainment. METHODS: Twin structural
      equation modeling was used to examine educational attainment as a moderator of
      heritability of hypertension. Participants were 4301 monozygotic and 3414
      dizygotic male Vietnam-era twins who provided data on both education (in years)
      and self-report of physician diagnosis of hypertension or medication usage.
      RESULTS: Heritability was 17 points lower among co-twins concordant for
      educational attainment of < or =14 years (0.46, 95% CI = 0.32-0.57) relative to
      co-twins concordant for >14 years of education (0.63, 95% CI = 0.54-0.71). The
      significant moderation of the heritability (p = .04) was confirmed in twin models
      examining educational attainment as a continuous moderator of hypertension.
      CONCLUSIONS: These results demonstrate that the expression of genetic
      vulnerability to hypertension can vary as a function of environmental factors,
      including education level, and that nongenetic pathways may differentially
      contribute to risk among those with fewer years of education.

PMID- 18725433
TI  - Patterns of objective physical functioning and perception of mood and fatigue in
      posttreatment breast cancer patients and healthy controls: an ambulatory
      psychophysiological investigation.
AB  - OBJECTIVE: To monitor objective physiological and self-report measures among
      apparently disease-free breast cancer patients (n = 33) in the first 2 years of
      posttreatment recovery, using a cross-sectional design, and compare findings with
      women without histories of cancer or other serious disorders (n =33). Time-since
      treatment also served as an independent variable. Few studies have examined
      adjustment of breast cancer patients after primary treatment or objectively
      characterized posttreatment, everyday patterns of functioning. METHODS: A 24-hour
      ambulatory minute-by-minute cardiorespiratory functioning and accelerometry
      activity were measured during one day, together with multiple repeated
      assessments of mood and fatigue. Traditional retrospective measures of well-being
      were also evaluated. Our ambulatory methodology permitted estimation of
      physiological rhythms of cardiorespiratory and accelerometry activity. RESULTS:
      Patients reported lower ambulatory levels of energy and poorer mood during the
      daytime than controls. Time-since-treatment was related directly to both
      momentary mood and energy as well as to objective measures of activity and
      respiratory parameters. Retrospective self-reports of impaired mood and symptoms
      persisted in patients, independently of time-since-treatment and of ambulatory
      physical or physiological activity. Ambulatory self-report data were associated
      with concurrent respiratory measures. Chemotherapy-related elevation of heart
      rate was found but was unrelated to self-report measures. CONCLUSIONS: Impaired
      sense of well being based on retrospective measures is not associated with
      pattern of physical or physiological functioning after treatment for breast
      cancer. However, ambulatory, momentary levels of mood and fatigue seem to be
      related to concurrent ventilatory activity and time-since-treatment. This is the
      first investigation that relates ambulatory and retrospective measures of affect
      and fatigue to concurrent, real-life physical functioning.

PMID- 18725434
TI  - Covariance between psychological and endocrine responses to pharmacological
      challenge and psychosocial stress: a question of timing.
AB  - OBJECTIVE: To test if the covariance of hypothalamus-pituitary-adrenal (HPA) axis
      and subjective-psychological responses to stress is dependent on different
      dynamics of these systems. Although stress theories typically assume substantial
      correlations of psychological and endocrine stress responses, studies have
      produced inconsistent results. One reason for this might be imperfect coupling of
      the different stress response systems. However, inconsistent correlations might
      also be a result of different on-/offsets of these stress responses, i.e.,
      specific dynamics of the systems. METHODS: HPA axis indicators and subjective
      psychological states were repeatedly and synchronously measured in a
      pharmacological challenge test (injection of corticotropin-releasing hormone and
      infusion of arginine vasopressin; Study 1; n = 42) and a psychosocial stress
      situation (Trier Social Stress Test; Study 2; n = 219). Cross-correlation
      analysis was used to test for lag effects in HPA axis reactivity and
      psychoendocrine responses. RESULTS: Analyses revealed high cross-correlations of
      adrenocorticotropic hormone with cortisol responses (up to r = .80 in Study 1 and
      r = .56 in Study 2) and positive associations of psychological with endocrine
      stress responses (up to r = .48 in Study 1 and r = .54 in Study 2) at nonzero
      lags. Subjective-psychological responses preceded HPA axis responses. Moreover,
      high levels of cortisol were associated with lower later levels of anxiety and
      activation. CONCLUSIONS: The findings suggest that psychoendocrine stress
      responses are more closely coupled than previous studies suggested. Due to
      different dynamics of the systems, endocrine responses lag behind psychological
      responses.

PMID- 18725435
TI  - Staphylococcus aureus PBP4 is essential for beta-lactam resistance in community
      acquired methicillin-resistant strains.
AB  - Recent cases of infections caused by community-acquired methicillin-resistant
      Staphylococcus aureus (MRSA) (CA-MRSA) strains in healthy individuals have raised
      concerns worldwide. CA-MRSA strains differ from hospital-acquired MRSAs by virtue
      of their genomic background and increased virulence in animal models. Here, we
      show that in two common CA-MRSA isolates, USA300 and MW2 (USA400), a loss of
      penicillin binding protein 4 (PBP4) is sufficient to cause a 16-fold reduction in
      oxacillin and nafcillin resistance, thus demonstrating that mecA, encoding PBP2A,
      is not the sole determinant of methicillin resistance in CA-MRSA. The loss of
      PBP4 was also found to severely affect the transcription of PBP2 in cells after
      challenge with oxacillin, thus leading to a significant decrease in peptidoglycan
      cross-linking. Autolysis, which is commonly associated with the killing mechanism
      of penicillin and beta-lactams, does not play a role in the reduced resistance
      phenotype associated with the loss of PBP4. We also showed that cefoxitin, a
      semisynthetic beta-lactam that binds irreversibly to PBP4, is synergistic with
      oxacillin in killing CA-MRSA strains, including clinical CA-MRSA isolates. Thus,
      PBP4 represents a major target for drug rediscovery against CA-MRSA, and a
      combination of cefoxitin and synthetic penicillins may be an effective therapy
      for CA-MRSA infections.

PMID- 18725436
TI  - Effect of electrical current on the activities of antimicrobial agents against
      Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis
      biofilms.
AB  - Bacterial biofilms are resistant to conventional antimicrobial agents. Prior in
      vitro studies have shown that electrical current (EC) enhances the activities of
      aminoglycosides, quinolones, and oxytetracycline against Pseudomonas aeruginosa,
      Klebsiella pneumoniae, Staphylococcus epidermidis, Escherichia coli, and
      Streptococcus gordonii. This phenomenon, known as the bioelectric effect, has
      been only partially defined. The purpose of this work was to study the in vitro
      bioelectric effect on the activities of 11 antimicrobial agents representing a
      variety of different classes against P. aeruginosa, methicillin-resistant
      Staphylococcus aureus (MRSA), and S. epidermidis. An eight-channel current
      generator/controller and eight chambers delivering a continuous flow of fresh
      medium with or without antimicrobial agents and/or EC to biofilm-coated coupons
      were used. No significant decreases in the numbers of log(10) CFU/cm(2) were seen
      after exposure to antimicrobial agents alone, with the exception of a 4.57-log
      unit reduction for S. epidermidis and trimethoprim-sulfamethoxazole. We detected
      a statistically significant bioelectric effect when vancomycin plus 2,000
      microamperes EC were used against MRSA biofilms (P = 0.04) and when daptomycin
      and erythromycin were used in combination with 200 or 2,000 microamperes EC
      against S. epidermidis biofilms (P = 0.02 and 0.0004, respectively). The results
      of these experiments indicate that the enhancement of the activity of
      antimicrobial agents against biofilm organisms by EC is not a generalizable
      phenomenon across microorganisms and antimicrobial agents.

PMID- 18725437
TI  - Is 60 days of ciprofloxacin administration necessary for postexposure prophylaxis
      for Bacillus anthracis?
AB  - Sixty days of ciprofloxacin administration at 500 mg every 12 h is currently
      recommended for the prophylaxis of inhalational exposure to Bacillus anthracis.
      We examined Bacillus anthracis (Delta-Sterne strain) in our hollow-fiber
      infection model. We measured the ciprofloxacin concentrations achieved and the
      number of organisms present before heat shock (total population) and after heat
      shock (spore population). We fit a mathematical model to these data. Monte Carlo
      simulation with differing initial spore burdens (3, 5, and 6.9 log(10) CFU/ml)
      demonstrated that 35 days of this regimen would completely clear the spore burden
      in 95% of patients. Durations of 110 days did not achieve 99.9% eradication,
      irrespective of initial burden, because of between-patient variance in drug
      pharmacokinetics. Given the absence of person-to-person transmission for Bacillus
      anthracis, adverse drug effects with long-term ciprofloxacin administration, and
      the possibility of engendering resistance in bodily flora, shorter prophylaxis
      duration should be given consideration, along with careful monitoring of all
      exposed individuals.

PMID- 18725438
TI  - Pharmacodynamic modeling of aminoglycosides against Pseudomonas aeruginosa and
      Acinetobacter baumannii: identifying dosing regimens to suppress resistance
      development.
AB  - To facilitate optimal dosing regimen design, we previously developed a
      mathematical model using time-kill study data to predict the responses of
      Pseudomonas aeruginosa to various pharmacokinetic profiles of meropenem and
      levofloxacin. In this study, we extended the model to predict the activities of
      gentamicin and amikacin exposures against P. aeruginosa and Acinetobacter
      baumannii, respectively. The input data were from a time-kill study with 10(7)
      CFU/ml of bacteria at baseline. P. aeruginosa ATCC 27853 was exposed to
      gentamicin (0 to 16x MIC; MIC = 2 mg/liter), and A. baumannii ATCC BAA 747 was
      exposed to amikacin (0 to 32x MIC; MIC = 4 mg/liter) for 24 h. Using the
      estimates of the best-fit model parameters, bacterial responses to various
      fluctuating aminoglycoside exposures (half-life, 2.5 h) over 72 h were predicted
      via computer simulation. The computer simulations were subsequently validated
      using an in vitro hollow-fiber infection model with similar aminoglycoside
      exposures. A significant initial reduction in the bacterial burden was predicted
      for all gentamicin exposures examined. However, regrowth over time due to
      resistance emergence was predicted for regimens with a maximum concentration of
      the drug (C(max))/MIC (dosing frequency) of 4 (every 8 h [q8h]), 12 (q24h), and
      36 (q24h). Sustained suppression of bacterial populations was forecast with a
      C(max)/MIC of 30 (q12h). Similarly, regrowth and suppression of A. baumannii were
      predicted and experimentally verified with a three-dimensional response surface.
      The mathematical model was reasonable in predicting extended bacterial responses
      to various aminoglycoside exposures qualitatively, based on limited input data.
      Our approach appears promising as a decision support tool for dosing regimen
      selection for antimicrobial agents.

PMID- 18725439
TI  - Efficacy of single-dose liposomal amphotericin B or micafungin prophylaxis in a
      neutropenic murine model of invasive pulmonary aspergillosis.
AB  - In a neutropenic murine model of invasive pulmonary aspergillosis, prophylaxis
      with single doses of liposomal amphotericin B or micafungin at >or=5 mg/kg of
      body weight improved animal survival and suppressed the lung fungal burden for up
      to 7 days after infection, demonstrating the potential utility of infrequent
      dosing with these antifungals.

PMID- 18725440
TI  - Real-time PCR detection of gyrA and parC mutations in Streptococcus pneumoniae.
AB  - Fluoroquinolone resistance in Streptococcus pneumoniae mainly involves stepwise
      mutations predominantly in the parC and gyrA genes. We have developed a single
      run real-time PCR assay for detection of the four most common mutations in the
      quinolone resistance-determining regions of these genes. This assay provides a
      useful tool for both clinical and epidemiological use.

PMID- 18725441
TI  - In vitro activities of tigecycline and 10 other antimicrobials against
      nonpigmented rapidly growing mycobacteria.
AB  - We evaluated the in vitro activities of tigecycline and 10 other antibiotics
      against clinical isolates of nonpigmented rapidly growing mycobacteria. Fifteen
      collection strains and 165 clinical isolates were included in the study.
      Tigecycline showed the highest activity among all antibiotics studied: all the
      strains were inhibited by 1 mg/liter.

PMID- 18725442
TI  - In vitro activity of OPT-80 tested against clinical isolates of toxin-producing
      Clostridium difficile.
AB  - Agar dilution antimicrobial susceptibility testing (CLSI, M11-A7, 2007) performed
      for 208 toxin-producing clinical isolates of Clostridium difficile resulted in
      OPT-80 MICs ranging from 0.06 to 1 microg/ml, with 90% of the isolates inhibited
      by a concentration of 0.5 microg/ml. The in vitro activity of OPT-80 was
      independent of the susceptibilities of isolates to nine other antimicrobial
      agents.

PMID- 18725443
TI  - In vitro activity of ceftaroline against Streptococcus pneumoniae isolates
      exhibiting resistance to penicillin, amoxicillin, and cefotaxime.

PMID- 18725444
TI  - Plasmid-mediated quinolone resistance determinants qnrA, qnrB, and qnrS among
      clinical isolates of Enterobacteriaceae in a Korean hospital.
AB  - Screening of 368 consecutive nonreplicate clinical isolates of Enterobacteriaceae
      resistant to nalidixic acid and at least one extended-spectrum beta-lactam
      revealed the presence of qnrA, qnrB, and qnrS determinants, and identified novel
      qnrB variants, in Citrobacter freundii isolates. This study also revealed, for
      the first time, the linkage of qnrB, armA, and extended-spectrum and/or AmpC-type
      beta-lactamase genes on large conjugative plasmids.

PMID- 18725445
TI  - Plasmodium falciparum strains harboring dihydrofolate reductase with the I164L
      mutation are absent in Malawi and Zambia even under antifolate drug pressure.
AB  - The Plasmodium falciparum dihydrofolate reductase (PfDHFR) enzyme is the target
      of pyrimethamine, a component of the antimalarial pyrimethamine-sulfadoxine.
      Resistance to this drug is associated primarily with mutations in the Pfdhfr
      gene. The I164L mutant allele is of particular interest, because strains
      possessing this mutation are highly resistant to pyrimethamine and to
      chlorproguanil, a component of chlorproguanil-dapsone. A recent study from Malawi
      reported this mutation at a prevalence of 4.7% in parasites from human
      immunodeficiency virus-positive pregnant women by using a real-time PCR method.
      These observations have huge implications for the use of pyrimethamine
      sulfadoxine, chlorproguanil-dapsone, and future antifolate-artemisinin
      combinations in Africa. It was imperative that this finding be rigorously tested.
      We identified a number of critical limitations in the original genotyping
      strategy. Using a refined and validated real-time PCR strategy, we report here
      that this mutation was absent in 158 isolates from Malawi and 42 isolates from
      Zambia collected between 2003 and 2005.

PMID- 18725446
TI  - Darunavir inhibitory quotient predicts the 48-week virological response to
      darunavir-based salvage therapy in human immunodeficiency virus-infected protease
      inhibitor-experienced patients.
AB  - The aim of this study was to evaluate the relationship between the virological
      response to darunavir-based salvage antiretroviral therapy and the darunavir
      genotypic and virtual inhibitory quotients (gIQ and vIQ, respectively). Thirty
      seven HIV-infected patients failing protease inhibitor-based antiretroviral
      regimens who started salvage therapy containing darunavir-ritonavir were
      prospectively studied. The primary outcome of the study was a viral load (VL) of
      <50 copies/ml at week 48. The trough concentrations of darunavir in plasma, the
      number of darunavir resistance mutations, the change in the 50% inhibitory
      concentration (IC(50)) of darunavir in the virtual phenotype, and the darunavir
      gIQ and vIQ were correlated with the virological outcome in regression analyses
      adjusted by the number of active drugs in the background regimen. The VL was <50
      copies/ml in 56.8% of patients at week 48. Changes in the VL were not
      significantly associated with the darunavir concentration (P = 0.304), the number
      of darunavir resistance mutations (P = 0.695), or the change in the IC(50) (P =
      0.750). However, patients with darunavir vIQs of >or=1.5 had a 12-fold greater
      chance of achieving a >or=1 log(10) reduction in the VL (odds ratio [OR], 12.7;
      95% confidence interval [95% CI], 1.9 to 81.6; P = 0.007), and a 5-fold greater
      chance of achieving a VL of <50 copies/ml (OR, 5.4; 95% CI, 1.2 to 24.5; P =
      0.028), at week 48 than patients with darunavir vIQs of <1.5. The positive and
      negative predictive values of this darunavir vIQ cutoff for achieving a VL of <50
      copies/ml at week 48 were 70% and 69%, respectively. The darunavir vIQ predicts
      virological response to darunavir-based salvage therapy better than the darunavir
      trough concentration or resistance mutations alone. We suggest targeting a
      darunavir vIQ of 1.5 for achieving long-term viral suppression.

PMID- 18725447
TI  - A plasmid-borne blaOXA-58 gene confers imipenem resistance to Acinetobacter
      baumannii isolates from a Lebanese hospital.
AB  - We investigated the basis of the carbapenem resistance of 17 multidrug-resistant
      Acinetobacter baumannii clinical isolates collected from 2004 to 2005 at the
      Saint George University Hospital in Beirut, Lebanon. A. baumannii isolates were
      clonally related and were susceptible to colistin and trimethoprim
      sulfamethoxazole, susceptible or intermediate to ampicillin-sulbactam and
      meropenem, and resistant to all other antimicrobials. Conjugation experiments
      demonstrated that resistance to imipenem could be transferred along with a
      plasmid containing the carbapenem-hydrolyzing oxacillinase bla(OXA-58) gene. The
      plasmid that we called pABIR was 29,823 bp in size and showed a novel mosaic
      structure composed of two origins of replication, four insertion sequence (IS)
      elements, and 28 open reading frames. The bla(OXA-58) gene was flanked by IS18
      and ISAba3 elements at the 5' and 3' ends, respectively. The production of the
      carbapenem-hydrolyzing oxacillinase OXA-58 was apparently the only mechanism for
      carbapenem resistance in A. baumannii isolates causing the outbreak at the
      Lebanese Hospital.

PMID- 18725448
TI  - Oseltamivir-ribavirin combination therapy for highly pathogenic H5N1 influenza
      virus infection in mice.
AB  - We studied the effects of a neuraminidase inhibitor (oseltamivir) and an
      inhibitor of influenza virus polymerases (ribavirin) against two highly
      pathogenic H5N1 influenza viruses. In vitro, A/Vietnam/1203/04 virus (clade 1)
      was highly susceptible to oseltamivir carboxylate (50% inhibitory concentration
      [IC(50)] = 0.3 nM), whereas A/Turkey/15/06 virus (clade 2.2) had reduced
      susceptibility (IC(50) = 5.5 nM). In vivo, BALB/c mice were treated with
      oseltamivir (1, 10, 50, or 100 mg/kg of body weight/day), ribavirin (37.5, 55, or
      75 mg/kg/day), or the combination of both drugs for 8 days, starting 4 h before
      virus inoculation. Monotherapy produced a dose-dependent antiviral effect against
      the two H5N1 viruses in vivo. Three-dimensional analysis of the drug-drug
      interactions revealed that oseltamivir and ribavirin interacted principally in an
      additive manner, with several exceptions of marginal synergy or marginal
      antagonism at some concentrations. The combination of ribavirin at 37.5 mg/kg/day
      and oseltamivir at 1 mg/kg/day and the combination of ribavirin at 37.5 mg/kg/day
      and oseltamivir at 10 mg/kg/day were synergistic against A/Vietnam/1203/04 and
      A/Turkey/15/06 viruses, respectively. These optimal oseltamivir-ribavirin
      combinations significantly inhibited virus replication in mouse organs, prevented
      the spread of H5N1 viruses beyond the respiratory tract, and abrogated the
      cytokine response (P < 0.01). Importantly, we observed clear differences between
      the efficacies of the drug combinations against two H5N1 viruses: higher doses
      were required for the protection of mice against A/Turkey/15/06 virus than for
      the protection of mice against A/Vietnam/1203/04 virus. Our preliminary results
      suggest that oseltamivir-ribavirin combinations can have a greater or lesser
      antiviral effect than monotherapy, depending on the H5N1 virus and the
      concentrations used.

PMID- 18725449
TI  - Dominance of blaCTX-M within an Australian extended-spectrum beta-lactamase gene
      pool.
AB  - bla(CTX-M) genes, particularly bla(CTX-M-15), are the dominant extended-spectrum
      beta-lactamase (ESBL) genes among clinical isolates of Escherichia coli and
      Klebsiella pneumoniae in Sydney, Australia, where we also found one example of
      bla(CTX-M-62), encoding a novel enzyme conferring ceftazidime resistance. ESBL
      genes were present in diverse community isolates and in a variety of associated
      conjugative plasmids.

PMID- 18725450
TI  - Characterization of TolC efflux pump proteins from Pasteurella multocida.
AB  - Two TolC homologs, PM0527 and PM1980, were identified for Pasteurella multocida.
      A pm0527 mutant displayed increased susceptibility to a range of chemicals,
      including rifampin (512-fold) and acridine orange (128-fold). A pm1980 mutant
      showed increased susceptibility to rifampin, ceftazidime, and vancomycin.

PMID- 18725451
TI  - Proposed MIC and disk diffusion microbiological cutoffs and spectrum of activity
      of retapamulin, a novel topical antimicrobial agent.
AB  - Retapamulin, the first pleuromutilin antimicrobial agent approved for the topical
      treatment of skin infections in humans, was tested against 987 clinical isolates
      representing 30 species and/or resistance groups. MICs were determined along with
      disk diffusion zone diameters using a 2-microg disk. Population distribution and
      MIC versus disk zone diameter scattergrams were analyzed to determine
      microbiological MIC cutoff values and inhibition zone correlates. Minimum
      bactericidal concentrations were performed on a smaller subset of key species.
      The retapamulin MIC(90) against 234 Staphylococcus aureus isolates and 110
      coagulase-negative staphylococci was 0.12 microg/ml. Retapamulin MIC(90)s ranged
      from 0.03 to 0.06 microg/ml against beta-hemolytic streptococci including 102
      Streptococcus pyogenes, 103 Streptococcus agalactiae, 59 group C Streptococcus,
      and 71 group G Streptococcus isolates. The MIC(90) against 55 viridans group
      streptococci was 0.25 microg/ml. Retapamulin had very little activity against 151
      gram-negative bacilli and most of the Enterococcus species tested. Based on the
      data from this study, for staphylococci, MICs of <or=0.5, 1, and >or=2 microg/ml
      with corresponding disk diffusion values of >or=20 mm, 17 to 19 mm, and <or=16 mm
      can be proposed for susceptible, intermediate, and resistant microbiological
      cutoffs, respectively. For beta-hemolytic streptococci, a susceptible-only MIC of
      <or=0.25 microg/ml with a corresponding disk diffusion value of >or=15 mm can be
      proposed for susceptible-only microbiological cutoffs.

PMID- 18725452
TI  - Genetic basis of multidrug resistance in Acinetobacter baumannii clinical
      isolates at a tertiary medical center in Pennsylvania.
AB  - A total of 49 unique clinical isolates of multidrug-resistant (MDR) Acinetobacter
      baumannii identified at a tertiary medical center in Pittsburgh, Pennsylvania,
      between August 2006 and September 2007 were studied for the genetic basis of
      their MDR phenotype. Approximately half of all A. baumannii clinical isolates
      identified during this period qualified as MDR, defined by nonsusceptibility to
      three or more of the antimicrobials routinely tested in the clinical microbiology
      laboratory. Among the MDR isolates, 18.4% were resistant to imipenem. The
      frequencies of resistance to amikacin and ciprofloxacin were high at 36.7% and
      95.9%, respectively. None of the isolates was resistant to colistin or
      tigecycline. The presence of the carbapenemase gene bla(OXA-23) and the 16S rRNA
      methylase gene armA predicted high-level resistance to imipenem and amikacin,
      respectively. bla(OXA-23) was preceded by insertion sequence ISAba1, which likely
      provided a potent promoter activity for the expression of the carbapenemase gene.
      The structure of the transposon defined by ISAba1 differed from those reported in
      Europe, suggesting that ISAba1-mediated acquisition of bla(OXA-23) may occur as
      an independent event. Typical substitutions in the quinolone resistance
      determining regions of the gyrA and parC genes were observed in the ciprofloxacin
      resistant isolates. Plasmid-mediated quinolone resistance genes, including the
      qnr genes, were not identified. Fifty-nine percent of the MDR isolates belonged
      to a single clonal group over the course of the study period, as demonstrated by
      pulsed-field gel electrophoresis.

PMID- 18725453
TI  - The beta-galactoside binding immunomodulatory lectin galectin-3 reverses the
      desensitized state induced in neutrophils by the chemotactic peptide f-Met-Leu
      Phe: role of reactive oxygen species generated by the NADPH-oxidase and
      inactivation of the agonist.
AB  - Neutrophils interacting with a chemoattractant gradually become nonresponsive to
      further stimulation by the same agonist, a process known as desensitization.
      Receptor desensitization is a highly regulated process that involves different
      mechanisms depending on which receptor-ligand pair that is studied. Galectin-3, a
      member of a large family of beta-galactoside-binding lectins, has been suggested
      to be a regulator of the inflammatory process, augmenting or directly triggering
      the neutrophil functional repertoire. We show here that the desensitized state of
      neutrophils interacting with the chemotactic peptide fMLF is broken by galectin-3
      and that this is achieved through an oxygen radical-mediated inactivation of the
      chemoattractant. The effect was inhibited by the competitor lactose and required
      the affinity of galectin-3 for N-acetyllactosamine, a saccharide typically found
      on cell surface glycoproteins. The latter was shown using a galectin-3 mutant
      that lacked N-acetyllactosamine binding activity, and this protein was not
      active. The mechanism behind the inactivation of the chemoattractant was found to
      depend on the ability of galectin-3 to induce a neutrophil generation/secretion
      of reactive oxygen species which in combined action with myeloperoxidase
      inactivated the peptides.

PMID- 18725454
TI  - High-resolution structure of the stable plasminogen activator inhibitor type-1
      variant 14-1B in its proteinase-cleaved form: a new tool for detailed interaction
      studies and modeling.
AB  - Wild-type plasminogen activator inhibitor type-1 (PAI-1) rapidly converts to the
      inactive latent state under conditions of physiological pH and temperature. For
      in vivo studies of active PAI-1 in cell culture and in vivo model systems, the 14
      1B PAI-1 mutant (N150H-K154T-Q319L-M354I), with its stabilized active
      conformation, has thus become the PAI-1 of choice. As a consequence of the
      increased stability, the only two forms likely to be encountered are the active
      or the cleaved form, the latter either free or complexed with target proteinase.
      We hereby report the first structure of the stable 14-1B PAI-1 variant in its
      reactive center cleaved form, to a resolution of 2.0 A. The >99% complete
      structure represents the highest resolved structure of free cleaved PAI-1. This
      high-resolution structure should be of great use for drug target development and
      for modeling protein-protein interactions such as those of PAI-1 with
      vitronectin.

PMID- 18725455
TI  - Structural evidence for substrate-induced synergism and half-sites reactivity in
      biotin carboxylase.
AB  - Bacterial acetyl-CoA carboxylase is a multifunctional biotin-dependent enzyme
      that consists of three separate proteins: biotin carboxylase (BC), biotin
      carboxyl carrier protein (BCCP), and carboxyltransferase (CT). Acetyl-CoA
      carboxylase is a potentially attractive target for novel antibiotics because it
      catalyzes the first committed step in fatty acid biosynthesis. In the first half
      reaction, BC catalyzes the ATP-dependent carboxylation of BCCP. In the second
      half-reaction, the carboxyl group is transferred from carboxybiotinylated BCCP to
      acetyl-CoA to produce malonyl-CoA. A series of structures of BC from several
      bacteria crystallized in the presence of various ATP analogs is described that
      addresses three major questions concerning the catalytic mechanism. The structure
      of BC bound to AMPPNP and the two catalytically essential magnesium ions resolves
      inconsistencies between the kinetics of active-site BC mutants and previously
      reported BC structures. Another structure of AMPPNP bound to BC shows the
      polyphosphate chain folded back on itself, and not in the correct (i.e.,
      extended) conformation for catalysis. This provides the first structural evidence
      for the hypothesis of substrate-induced synergism, which posits that ATP binds
      nonproductively to BC in the absence of biotin. The BC homodimer has been
      proposed to exhibit half-sites reactivity where the active sites alternate or
      "flip-flop" their catalytic cycles. A crystal structure of BC showed the ATP
      analog AMPPCF(2)P bound to one subunit while the other subunit was unliganded.
      The liganded subunit was in the closed or catalytic conformation while the
      unliganded subunit was in the open conformation. This provides the first
      structural evidence for half-sites reactivity in BC.

PMID- 18725456
TI  - Crystal structure of the human receptor activity-modifying protein 1
      extracellular domain.
AB  - Receptor activity-modifying protein (RAMP) 1 forms a heterodimer with calcitonin
      receptor-like receptor (CRLR) and regulates its transport to the cell surface.
      The CRLR.RAMP1 heterodimer functions as a specific receptor for calcitonin gene
      related peptide (CGRP). Here, we report the crystal structure of the human RAMP1
      extracellular domain. The RAMP1 structure is a three-helix bundle that is
      stabilized by three disulfide bonds. The RAMP1 residues important for cell
      surface expression of the CRLR.RAMP1 heterodimer are clustered to form a
      hydrophobic patch on the molecular surface. The hydrophobic patch is located near
      the tryptophan residue essential for binding of the CGRP antagonist, BIBN4096BS.
      These results suggest that the hydrophobic patch participates in the interaction
      with CRLR and the formation of the ligand-binding pocket when it forms the
      CRLR.RAMP1 heterodimer.

PMID- 18725457
TI  - Identification of a nuclear localization signal in suppressor of cytokine
      signaling 1.
AB  - Suppressor of cytokine signaling (SOCS) proteins are inducible feedback
      inhibitors of janus kinase and signal transducer and activators of transcription
      signaling pathways. In addition, SOCS1 has been identified to regulate stability
      of nuclear NF-kappaB subunits. However, details about the regulation of the
      nuclear pool of SOCS1 are unknown. Using different experimental approaches, we
      observed that SOCS1 but no further SOCS family members localized to the nucleus
      when expressed in various cell lines. Nuclear transport was confirmed for
      endogenous SOCS1 in macrophages stimulated with IFN-gamma. Sequence analysis
      revealed a bipartite nuclear localization signal (NLS) located between the src
      homology 2 (SH2) domain and the SOCS box of SOCS1. Deletion of this region,
      introduction of a series of R/A point mutations, or substitution of this sequence
      with the respective region of SOCS3 resulted in loss of nuclear localization.
      Fusion of the SOCS1-NLS to cytokine-inducible SH2 region containing protein (CIS)
      resulted in nuclear localization of this otherwise cytoplasmic protein. SOCS1
      mutants with loss of nuclear localization were still effective in suppressing IFN
      alpha-mediated STAT1 tyrosine phosphorylation. However, they showed decreased
      inhibition of IFN-gamma-mediated induction of CD54. The results identify a
      hitherto unknown transport of SOCS1 into the nucleus which extends the spectrum
      of SOCS1 inhibitory activity.

PMID- 18725458
TI  - Epoxyeicosatrienoic acids and the soluble epoxide hydrolase are determinants of
      pulmonary artery pressure and the acute hypoxic pulmonary vasoconstrictor
      response.
AB  - Recent findings have indicated a role for cytochrome P-450 (CYP) epoxygenase
      derived epoxyeicosatrienoic acids (EETs) in acute hypoxic pulmonary
      vasoconstriction (HPV). Given that the intracellular concentration of EETs is
      determined by the soluble epoxide hydrolase (sEH), we assessed the influence of
      the sEH and 11,12-EET on pulmonary artery pressure and HPV in the isolated mouse
      lung. In lungs from wild-type mice, HPV was significantly increased by sEH
      inhibition, an effect abolished by pretreatment with CYP epoxygenase inhibitors
      and the EET antagonist 14,15-EEZE. HPV and EET production were greater in lungs
      from sEH(-/-) mice than from wild-type mice and sEH inhibition had no further
      effect on HPV, while MSPPOH and 14,15-EEZE decreased the response. 11,12-EET
      increased pulmonary artery pressure in a concentration-dependent manner and
      enhanced HPV via a Rho-dependent mechanism. Both 11,12-EET and hypoxia elicited
      the membrane translocation of a transient receptor potential (TRP) C6-V5 fusion
      protein, the latter effect was sensitive to 14,15-EEZE. Moreover, while acute
      hypoxia and 11,12-EET increased pulmonary pressure in lungs from TRPC6(+/-) mice,
      lungs from TRPC6(-/-) mice did not respond to either stimuli. These data
      demonstrate that CYP-derived EETs are involved in HPV and that EET-induced
      pulmonary contraction under normoxic and hypoxic conditions involves a TRPC6
      dependent pathway.

PMID- 18725459
TI  - Quantitative intracellular magnetic nanoparticle uptake measured by live cell
      magnetophoresis.
AB  - Superparamagnetic iron oxide (SPIO) particles have been used successfully as an
      intracellular contrast agent for nuclear MRI cell tracking in vivo. We present a
      method of detecting intracellular SPIO colloid uptake in live cells using cell
      magnetophoresis, with potential applications in measuring intracellular MRI
      contrast uptake. The method was evaluated by measuring shifts in mean and
      distribution of the cell magnetophoretic mobility, and the concomitant changes in
      population frequency of the magnetically positive cells when compared to the
      unmanipulated negative control. Seven different transfection agent (TA) -SPIO
      complexes based on dendrimer, lipid, and polyethylenimine compounds were used as
      test standards, in combination with 3 different cell types: mesenchymal stem
      cells, cardiac fibroblasts, and cultured KG-1a hematopoietic stem cells.
      Transfectol (TRA) -SPIO incubation resulted in the highest frequency of
      magnetically positive cells (>90%), and Fugene 6 (FUG) -SPIO incubation the
      lowest, below that when using SPIO alone. A highly regular process of cell
      magnetophoresis was amenable to intracellular iron mass calculations. The results
      were consistent in all the cell types studied and with other reports. The cell
      magnetophoresis depends on the presence of high-spin iron species and is
      therefore expected to be directly related to the cell MRI contrast level.

PMID- 18725461
TI  - In reference to lamborn et Al. (Neuro-oncology. 2008;10:162-170).

PMID- 18725460
TI  - Phase II preradiation R115777 (tipifarnib) in newly diagnosed GBM with residual
      enhancing disease.
AB  - Glioblastoma multiforme (GBM) is a lethal primary malignant brain tumor in
      adults. R115777 (tipifarnib) is an oral agent with antiproliferative effects,
      being a potent and selective inhibitor of farnesyltransferase. This multicenter,
      open-label phase II study was designed to evaluate the efficacy and safety of
      R115777 given after surgery and prior to radiation in patients with newly
      diagnosed and residual enhancing GBM. Following surgery, an MRI confirmed the
      presence of residual enhancing tumor. Patients on enzyme-inducing antiseizure
      drugs (EIASDs) received 600 mg twice per day, and those not on EIASDs received
      300 mg twice per day. One to three monthly cycles of R115777 were administered,
      and radiation was initiated with progression or after three cycles. A cycle
      consisted of 3 weeks of continuous R115777 followed by a 1-week rest. MRI was
      done monthly. The primary end point was overall survival; secondary end points
      were tumor response rate and toxicity. A total of 28 confirmed GBM patients
      entered the study; 15 patients (54%) were on EIASDs. The overall median time of
      survival was 7.7 months. There were no tumor responses. Eight patients (29%) had
      stable disease as the best response. The study was stopped early due to
      progression of the disease in 12 patients (48%). A total of 24 patients (85%)
      were off study before the planned treatment schedule for radiation therapy.
      R115777 administered prior to radiation therapy in patients with newly diagnosed
      GBM and residual enhancing disease did not result in any measurable responses or
      improvement in survival. R115777 administered prior to radiation therapy is not
      recommended for patients with newly diagnosed GBM.

PMID- 18725462
TI  - Remembering Benjamin Franklin Trump.

PMID- 18725463
TI  - Cervical, mandibular, and parotid lymph nodes of dogs naturally infected with
      Leishmania infantum: a histopathologic and immunohistochemistry study and its
      correlation with facial skin lesions.
AB  - The parasite load in cervical, mandibular, and parotid lymph nodes and in the
      skin of the nose and the pinna from dogs infected with Leishmania infantum were
      investigated by histologic and immunohistochemical studies. Twenty-two infected
      dogs with and without signs of infection were examined to demonstrate correlation
      of signs with parasite load and the correlation of facial skin lesions with
      parasites in regional lymph nodes. Chronic inflammation of the skin was
      demonstrated in infected dogs that had no gross skin lesions, confirming that
      normal-appearing skin can harbor the parasite, likely playing a role in
      transmission. Dogs with facial skin lesions showed a higher parasite load in
      parotid lymph nodes than dogs without lesions of the facial skin, based on
      Leishman-Donovan unit analysis. Based on immunohistochemical analysis, parasite
      load in parotid and cervical nodes was correlated with that of skin of the nose
      and pinna, as was the parasite load in mandibular lymph nodes and skin of the
      external nose. We demonstrated a logical involvement of the lymphatic vessels and
      their specific anatomic draining sites.

PMID- 18725464
TI  - Arterial calcification in race horses.
AB  - Calcification of large arteries has been sporadically reported in horses. The
      pathogenesis is still unknown, but recent studies in humans suggest that this is
      a regulated biomineralizing process. This study surveyed the prevalence,
      distribution, and severity of vascular calcification in Thoroughbred and
      Standardbred racehorses. Histopathologic, ultrastructural imaging, and energy
      dispersive X-ray elemental analyses were used to examine the lesions.
      Calcification of the tunica media, predominantly the pulmonary artery, was found
      in 82% of horses (83/101). Young adult horses (mean [SD] age in years, 4.44 +/-
      2.17) of both breeds and sexes were similarly affected. Lesions appeared as white
      to-yellowish, hard, and gritty plaques of variable size. On microscopic
      examination, elastic fibers within the tunica media were thinned, fragmented, and
      calcified, and surrounded by dense collagen matrix. Elemental analysis showed
      distinct peaks for calcium and phosphorus, consistent with hydroxyapatite
      mineral. The frequent occurrence of calcification in the tunica media of large
      pulmonary arteries of young racing horses indicates the need to investigate its
      pathogenesis and potential clinical implications.

PMID- 18725465
TI  - Neuropathology of italian cats in feline spongiform encephalopathy surveillance.
AB  - Feline spongiform encephalopathy (FSE) is a transmissible spongiform
      encephalopathy associated with the consumption of feedstuffs contaminated with
      tissue from bovine spongiform encephalopathy-affected cattle and characterized by
      the accumulation in the central nervous system of an abnormal isoform of the
      prion protein (PrP(sc)). Clinically, it presents as a progressive fatal
      neurologic syndrome that is not easily distinguished from other feline neurologic
      conditions. Most cases of FSE have been reported in England, where it was first
      detected in 1990, but a few cases have been reported from other European
      countries. To identify possible cases of FSE in Italy, the Italian Ministry of
      Health funded a 2-year surveillance project during which the brains from 110
      domestic cats with neurologic signs were evaluated histologically for spongiform
      encephalopathy and immunohistochemically to detect PrP(sc). Although no cases of
      FSE were found, the study proved useful in monitoring the Italian cat population
      for other neurologic diseases: neoplasia (21.8%), toxic-metabolic encephalopathy
      (18.2%), granulomatous encephalitis (15.5%), suppurative encephalitis (4.6%),
      trauma (3.6%), circulatory disorders (3.6%), degeneration (2.7%), nonsuppurative
      encephalitis (2.7%), and neuromuscular diseases (1.8%). No histologic lesions
      were found in 20% of the brains, and samples from 5.5% of the cats were rejected
      as unsuitable.

PMID- 18725466
TI  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      in four calves.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA),
      or Bland-White-Garland syndrome, is a rare congenital malformation described in
      children and adults. In this condition, the left coronary artery, which normally
      originates from the left coronary sinus in the aorta, instead originates from the
      pulmonary trunk, which results in retrograde flow of blood away from the
      myocardium into the lower-pressure pulmonary artery. Myocardial hypoxic-ischemic
      injury results in cardiac dysfunction, failure, and eventually in patient death
      if not surgically repaired. This report describes gross and microscopic findings
      in 4 beef calves with ALCAPA. All the calves had a history of being found dead
      with few or no premonitory signs, 2 shortly after sudden strenuous exercise.
      Gross necropsy lesions suggestive of heart failure included cardiomegaly with
      atrial and ventricular dilation and/or ventricular hypertrophy, and hepatomegaly.
      Dissection of each heart revealed the origin of the left coronary artery arising
      in the pulmonary trunk above the anterior cusp of the pulmonic valve. No
      degeneration; mineralization; and fiber loss, with replacement by fibrous
      connective tissue, predominantly in the left ventricular papillary muscle and the
      interventricular septum. Changes observed in the liver and lungs, including
      hepatomegaly, sinusoidal congestion, centrilobular fibrosis, and pulmonary
      congestion, edema, and intra-alveolar pigment-laden macrophages were consistent
      with heart failure.

PMID- 18725467
TI  - Porcine circovirus 2 inclusion bodies in pulmonary and renal epithelial cells.
AB  - Porcine circovirus 2 (PCV2) is the cause of postweaning multisystemic wasting
      syndrome (PMWS). The most common lesions of PMWS are lymphohistiocytic to
      granulomatous lymphadenitis, interstitial pneumonia and interstitial nephritis,
      with intracytoplasmic amphophilic botryoid inclusion bodies in macrophages. In
      addition to these typical changes, intracytoplasmic botryoid inclusion bodies
      were observed in bronchial, bronchial glandular, and renal tubular epithelium of
      several pigs from 4 different farms in Western and Eastern Canada. PCV2 inclusion
      bodies were demonstrated to be located in the cytoplasm of epithelial cells by
      immunohistochemical staining for PCV2 and cytokeratin antigens and by
      ultrastructural demonstration of viral particles in the inclusion bodies within
      renal tubular epithelium.

PMID- 18725468
TI  - Systemic reactive angioendotheliomatosis-like syndrome in a steer presumed to be
      persistently infected with bovine viral diarrhea virus.
AB  - Unusual proliferative intravascular lesions were seen in multiple organs of a 2
      year-old Corriente steer presumed to be persistently infected with bovine viral
      diarrhea virus (BVDV), based on widespread immunohistochemical detection of BVDV
      antigen. Proliferations of spindle cells, which were immunohistochemically
      positive for von Willebrand factor-related antigen, partially-to-completely
      occluded vessel lumens and were supported by cells that were
      immunohistochemically positive for smooth muscle actin. Distribution and
      character of the intraluminal proliferations are strikingly similar to those
      described in feline systemic reactive angioendotheliomatosis, a rare entity of
      unknown cause. The presence of occasional intravascular thrombi suggests that the
      proliferative vasculopathy was associated with an underlying thrombotic process
      with immunohistochemical similarities to thrombotic thrombocytopenic purpura of
      humans. Death of the steer was due to hemorrhage from a castration wound, which
      may indicate thrombocytopenia or platelet dysfunction. The role of persistent
      BVDV infection in the formation of the intravascular lesions is unknown.

PMID- 18725469
TI  - Cervical spinal chordoma with chondromatous component in a dog.
AB  - A 7-year-old male Belgian Shepherd dog was presented with sudden onset of lateral
      recumbency and tetraparesis. At the level of the third cervical vertebra,
      magnetic resonance imaging demonstrated an intrameningeal and intramedullary mass
      lesion. The animal was subsequently euthanatized. A necropsy revealed a
      semitranslucent solid mass infiltrating dorsal and ventral dura mater and the
      spinal cord. Histologic examination revealed a lobulated pleomorphic mass, mainly
      resembling undifferentiated cartilage interspersed by spindle-shaped and
      polygonal cells with highly vacuolated cytoplasm (physaliphorous cells).
      Immunohistochemistry of the tumor cells demonstrated dual expression of vimentin
      and cytokeratin. Based on the histologic and immunohistochemical results, the
      diagnosis of a chordoma with chondromatous component was made.

PMID- 18725470
TI  - Characterization of uterine granular cell tumors in B6C3F1 mice: a
      histomorphologic, immunohistochemical, and ultrastructural study.
AB  - The granular cell tumor is most often a benign neoplasm of uncertain origin. Four
      uterine granular cell tumors in control and treated female B6C3F1 mice were
      identified in chronic studies at the National Toxicology Program. Two tumors
      occurred in untreated control animals and 2 in treated animals receiving
      different compounds. Tissue sections were evaluated histologically and stained
      with hematoxylin and eosin, periodic acid-Schiff with diastase resistance,
      Masson's trichrome, toluidine blue, phosphotungstic acid-hematoxylin, and stained
      immunohistochemically with a panel of antibodies to muscle (desmin, alpha smooth
      muscle actin), neural (S-100, neuron specific enolase), epithelial (wide-spectrum
      cytokeratin), and macrophage (F4/80) markers. The main histomorphologic feature
      of tumor cells was the presence of abundant cytoplasmic eosinophilic granules
      that stained positive for periodic acid-Schiff with diastase resistance. Tumors
      varied in appearance and were comprised of sheets and nests of round to polygonal
      cells with distinct borders. Nuclei were hyperchromatic, pleomorphic, and
      centrally to eccentrically located and often contained single nucleoli.
      Occasional multinucleated giant cells were observed. Tumors were pale pink and
      homogeneous with trichrome stain and negative with toluidine blue. Three tumors
      had positive to weakly positive immunoreactivity for desmin, and 1 was positive
      for alpha smooth muscle actin. Expression of S-100, wide-spectrum cytokeratin,
      and neuron-specific enolase was negative for all tumors. Ultrastructurally,
      prominent electron-dense cytoplasmic granules were abundant and contained
      secondary lysosomes with heterogeneous lysosomal contents. The characteristics of
      these uterine granular cell tumors were suggestive of a myogenic origin.

PMID- 18725471
TI  - Laboratory findings, histopathology, and immunophenotype of lymphoma in domestic
      ferrets.
AB  - Lymphoma is a common tumor in ferrets, but anatomic distribution,
      histomorphology, immunophenotype, laboratory abnormalities, and response to
      chemotherapy are incompletely defined. In this study, lymphoma was diagnosed by
      histopathology of tumor tissue in 29 ferrets ranging in age from 0.8 to 8.5
      years, including 12 males and 17 females. Tumors involved the viscera of the
      abdominal cavity (n = 11), thoracic cavity (n = 1), or abdominal and thoracic
      cavities (n = 7); the skin (n = 2); or the viscera of both body cavities plus
      other sites (n = 8). Microscopically, all tumors had diffuse architecture.
      Assessment by histomorphology and immunophenotype classified tumors as peripheral
      T-cell lymphoma (n = 17), anaplastic large T-cell lymphoma (n = 5), anaplastic
      large B-cell lymphoma (n = 4), diffuse large B-cell lymphoma (n = 1), and Hodgkin
      like lymphoma (n = 2). Cytologic evaluation of tumor tissue was diagnostic in 11
      of 13 cases. Twenty-two of 27 ferrets had anemia, 2 had leukemia, and 5 were
      neutropenic. Common comorbid disorders were adrenal disease (n = 27) and
      insulinoma (n = 6). Tumors most frequently involved mesenteric lymph nodes, while
      enlargement of peripheral lymph nodes was uncommon (n = 3). Ferrets with Hodgkin
      like lymphoma had massive enlargement of single lymph nodes. Mean survival of
      ferrets not immediately euthanized was 5.0 months (T-cell lymphoma) and 8.4
      months (B-cell lymphoma). Ferrets treated with chemotherapy survived an average
      of 4.3 months (T-cell lymphoma, n = 9) or 8.8 months (B-cell lymphoma, n = 4).
      Results indicate that lymphomas in ferrets most commonly affect abdominal
      viscera, may be amenable to cytologic diagnosis, are frequently associated with
      anemia and, in some cases, may be chemosensitive, resulting in relatively long
      survival times.

PMID- 18725472
TI  - Spontaneous tumors in domestic hamsters.
AB  - A total of 90 tumors from 85 domestic hamsters (70 Djungarian hamsters and 15
      Syrian hamsters) were examined by histology. In the Djungarian hamsters, 64
      neoplastic and 11 non-neoplastic lesions were identified, whereas 14 Syrian
      hamsters showed neoplastic disease, and one showed non-neoplastic disease. The
      Djungarian hamsters showed a high prevalence of neoplastic disease, similarly to
      laboratory Djungarian hamsters. In the Djungarian hamsters, almost all tumors
      were integumental, whereas hematopoietic tumors were the most common type in the
      Syrian hamsters. The most common integumental tumors in the Djungarian hamsters
      were mammary tumors, atypical fibromas and papillomas, and a spectrum of
      integumental tumors that have not been reported in laboratory Djungarian hamsters
      were identified. Most mammary tumors occurred in the females, whereas all
      atypical fibromas were observed in the males. In the Syrian hamsters,
      plasmacytomas and lymphomas were the most common tumors. The small number of
      Syrian hamsters in this study may reflect the low prevalence of spontaneous
      tumors seen in laboratory Syrian hamsters. The mean age of the affected hamsters
      was 19.8 months, which is relatively advanced. To our knowledge, this is the
      first comprehensive study of tumors in domestic hamsters.

PMID- 18725473
TI  - Malignant amelanotic melanoma behind the left eye in a female Crj:CD(SD)IGS rat:
      a case report.
AB  - A tumor behind the left eye in a female Crj:CD(SD)IGS rat was investigated
      histopathologically, immunohistopathologically, and electron microscopically. The
      tumor invaded and destroyed orbital tissues and bones. It consisted of various
      tumor cells; namely, spindle-shaped, epithelioid, anaplastic melanoma cells, and
      had prominent eosinophilic cytoplasm and nuclei with a greater variation in size.
      Immunohistochemically, almost all of the tumor cells were positive for
      antimelanoma, PNL2 antibody. Ultrastructurally, the tumor cells were rich in
      small vesicles containing fine granules and filamentous structures. This is the
      first report describing an amelanotic melanoma in the head of an albino rat.

PMID- 18725474
TI  - Naturally occurring multiple perineuriomas in a chicken (Gallus domesticus).
AB  - A 2-year-old, male Japanese native fowl (Gallus gallus domesticus) was presented
      with an inability to feed and torticollis. At a necropsy, there were cylindrical
      enlargements and yellow discoloration of multiple peripheral nerves, including
      nerves of the lumbosacral plexus, brachial plexus, and spinal ganglia. On
      histologic examination, these lesions consisted of diffuse proliferations of
      spindle cells with characteristic onion bulb-like structures around residual
      axons. The spindle cells were immunohistochemically positive for glucose
      transporter 1 (GLUT1) and negative for S-100 alpha/beta proteins. On the basis of
      microscopic, histologic, and immunohistochemical findings, the tumors were
      diagnosed as multiple perineuriomas.

PMID- 18725475
TI  - Ganglioneuroma of the brachial plexus in two cockatiels (Nymphicus hollandicus).
AB  - Ganglioneuroma involving the brachial plexus, paraspinal ganglia, and cervical
      thoracic spinal cord was diagnosed in 2 adult cockatiels (Nymphicus hollandicus).
      Both birds had a chronic 1-year history of ataxia and perching difficulty. At
      necropsy, each bird had a unilateral, firm, gelatinous white to tan multilobular
      mass at the thoracic inlet expanding and partially obliterating the brachial
      plexus and cervical spinal cord. Histologically, the masses were characterized by
      a locally infiltrative neoplasm comprised of spindloid cells forming streams and
      sheets with interspersed distinct neuron cell bodies consistent with ganglion
      cells. The spindloid cell population was immunohistochemically positive for
      neurofilament protein in one of the birds.

PMID- 18725476
TI  - Oviduct adenocarcinoma in some species of captive snakes.
AB  - This article reports 5 cases of oviduct adenocarcinoma in adult captive snakes
      from Smithsonian's National Zoological Park. This neoplasm was found in 1 of each
      of the following species: emerald tree boa (Corallus caninus), Amazonian tree boa
      (Corallus enydris enydris), Burmese rock python (Python molurus bivittatus),
      Northern pine snake (Pituophis melanoleucus melanoleucus), and corn snake (Elaphe
      guttata). Grossly, tan to red firm masses were found within oviducts in 3 cases.
      In an additional 2 cases, the primary tumor was detected only histologically.
      Microscopically, neoplasms were papillary, and often extended transmurally. The
      neoplastic cells were polygonal and organized in acini or cords, with often
      abundant fibrovascular stroma. Hemorrhages and necrosis were present in all
      cases. Inflammation, myxomatous material, desmoplasia, and bacteria were often
      observed. Histologic evidence of metastasis was present in all cases. Solid
      metastases were seen in all animals except the Northern pine snake and involved
      several organs including the liver, lung, and heart. Emboli of neoplastic cells
      were observed in all animals but the Burmese rock python and corn snake.

PMID- 18725477
TI  - REVIEW paper: pathophysiology of myocardial reperfusion injury: the role of
      genetically engineered mouse models.
AB  - Coronary heart disease is the leading cause of death worldwide, affecting
      millions of men and women each year. Following an acute myocardial infarction,
      early and successful reperfusion therapy with thrombolytic therapy or primary
      percutaneous coronary intervention plays an important role in minimizing tissue
      injury associated with cessation of blood flow. The process of restoring blood
      flow to the ischemic myocardium, however, can induce additional injury. This
      phenomenon, termed myocardial ischemia-reperfusion (MI-R) injury, can
      paradoxically reduce the beneficial effects of myocardial reperfusion. MI-R
      injury is characterized by the formation of oxygen radicals upon reintroduction
      of molecular oxygen to the ischemic tissue, resulting in widespread lipid and
      protein oxidative modifications, mitochondrial injury, and cell death. In
      addition, studies have shown that MI-R is characterized by an inappropriate
      immune response in the microcirculation, resulting in leukocyte-endothelial cell
      interactions mediated by the upregulation of both leukocyte and endothelial cell
      adhesion molecules. Furthermore, MI-R ameliorates the production of certain
      cardioprotective factors such as nitric oxide. Advances in the generation of
      genetically modified mouse models enable researchers to identify the functional
      importance of genes involved in these processes.

PMID- 18725478
TI  - Commentary: regulatory toxicology and the critical path: predicting long-term
      outcomes from short-term studies.

PMID- 18725479
TI  - REVIEW paper: mare reproductive loss syndrome.
AB  - An epidemic of early fetal loss (EFL), late fetal loss (LFL), fibrinous
      pericarditis, and unilateral uveitis which occurred during the spring of 2001,
      are together now known as the mare reproductive loss syndrome (MRLS). A similar
      epidemic with less intensity was reported during the same period of time from
      southern Ohio, West Virginia, and Tennessee. The same syndrome with lesser
      intensity recurred in 2002. The estimated economic loss from the syndrome in 2001
      and 2002 together was approximately $500 million. Both EFL and LFL were
      characterized by the absence of specific clinical signs in aborting mares.
      Nonhemolytic Streptococcus spp. and Actinobacillus spp. accounted for 65% of the
      organisms isolated from fetuses submitted for a postmortem during the MRLS period
      in 2001 and 2002. The pathologic findings in fetoplacental units of LFL included
      bronchopneumonia and funisitis, and there were no findings in EFL. Epidemiologic
      studies conducted in 2001 suggested an association between the presences of
      eastern tent caterpillars (ETC) in pastures with MRLS. Experimental studies in
      pregnant mares by exposure to ETC, or administration by stomach tube or with feed
      material, reproduced EFL and LFL. Similar experimental studies in mouse, rats,
      and goats with ETC were unsuccessful. Currently, 2 hypotheses are proposed for
      MRLS. One hypothesis proposes that an ETC-related toxin with secondary
      opportunistic bacterial invasion of the fetus leads to MRLS. The second
      hypothesis suggests that a breach of gastrointestinal mucosal integrity by hairs
      of ETC leads to a bacteremia and results in MRLS. In 2004, a similar equine
      abortion storm was reported from Australia and caterpillar exposure was
      identified as a risk factor for the abortion. In 2006, the syndrome was observed
      in Florida and New Jersey.

PMID- 18725480
TI  - Invasive micropapillary mammary carcinoma in a male cat: first report.

PMID- 18725484
TI  - Pilot study to assess the influence of beta-blockade on mitral regurgitant volume
      and left ventricular work in degenerative mitral valve disease.
AB  - BACKGROUND: A medical treatment that decreases the likelihood of left ventricular
      (LV) dysfunction or symptoms would benefit patients with moderate to severe
      degenerative mitral regurgitation. The aim of this pilot study was to determine
      the short-term effects of a beta-blocker on mitral regurgitant volume and LV work
      in these patients. METHODS AND RESULTS: Twenty-five patients with moderate or
      severe degenerative mitral regurgitation were randomized in a double-blind
      crossover study to the beta(1)-selective adrenergic blocker metoprolol (mean
      daily dose, 119 mg; range 23.75 to 190 mg) and placebo for 14+/-3 days. At the
      end of each treatment period, ascending aortic flow and LV stroke volume were
      measured by cardiac magnetic resonance imaging, and mitral regurgitant volume was
      calculated. On beta-blocker, heart rate decreased from 65+/-10 by 10+/-7 bpm
      (mean+/-SD) and systolic blood pressure decreased from 138+/-18 by 16+/-12 mm Hg
      (P<0.0001 for both). No significant change occurred in LV ejection fraction (from
      65+/-5%; change, -0.6+/-2.7%; P=0.3) or mitral regurgitant volume (from 59+/-36
      mL; change, 3+/-13 mL; P=0.3), but forward stroke volume increased from 89+/-21
      by 5+/-11 mL (P=0.03). Because heart rate was lower on metoprolol, cardiac output
      decreased from 5.68+/-1.04 by 0.56+/-0.78 L/min (P=0.001), but a greater decrease
      occurred in LV output, from 9.51+/-2.22 by 1.30+/-1.08 L/min (P<0.0001). Mitral
      regurgitant volume per minute decreased from 3.83+/-2.41 by 0.74+/-1.00 L/min
      (P=0.001). The decrease in LV work on beta-blocker (mean, 21%; 95% confidence
      interval, 15 to 27) was greater (P=0.001) than the decrease in cardiac output
      (mean, 9%; 95% confidence interval, 3 to 15). CONCLUSIONS: In this pilot study,
      short-term treatment with a beta-blocker did not change mitral regurgitant volume
      per beat but decreased LV work in patients with moderate to severe degenerative
      mitral regurgitation. Further research is needed to determine whether longer-term
      treatment with beta-blockers will decrease progressive LV dysfunction and
      symptomatic deterioration.

PMID- 18725485
TI  - Delayed arterial healing and increased late stent thrombosis at culprit sites
      after drug-eluting stent placement for acute myocardial infarction patients: an
      autopsy study.
AB  - BACKGROUND: The long-term safety of drug-eluting stents (DES) for acute
      myocardial infarction (AMI) remains uncertain. Using autopsy data, we evaluated
      the pathological responses of the stented segment in patients treated with DES
      for AMI and compared with patients with stable angina. METHODS AND RESULTS: From
      the CVPath Registry of 138 DES autopsies, we identified 25 patients who presented
      with AMI and had an underlying necrotic core with a ruptured fibrous cap. Twenty
      six patients who had stable angina with thick-cap fibroatheroma treated by DES
      were selected as controls. Histomorphometric analysis was performed in patients
      with >30-day stent duration. We compared the response to stenting at the culprit
      site in these 2 groups and to nonculprit sites within each stent. Late stent
      thrombosis was significantly less frequent in stable (11%) than in AMI (41%;
      P=0.04) patients. Although neointimal thickness in the AMI culprit site was
      significantly less (median, 0.04 mm; interquartile range [IQR], 0.02 to 0.09 mm),
      the prevalence of uncovered struts (49%; IQR, 16% to 96%), fibrin deposition
      (63+/-28%), and inflammation (35%; IQR, 27% to 49%) were significantly greater
      compared with the culprit site in stable patients (neointimal thickness: 0.11 mm
      [IQR, 0.07 to 0.21 mm], P=0.008; uncovered struts: 9% [IQR, 0% to 39%], P=0.01;
      fibrin: 36+/-27%, P=0.008; inflammation, 17% [IQR, 7% to 25%], P=0.003) and the
      nonculprit site within each stent. CONCLUSIONS: Vessel healing at the culprit
      site in AMI patients treated with DES is substantially delayed compared with the
      culprit site in patients receiving DES for stable angina, emphasizing the
      importance of underlying plaque morphology in the arterial response to DES. Our
      data suggest an increased risk of thrombotic complications in patients treated
      with DES for AMI.

PMID- 18725486
TI  - Fhl-1, a new key protein in pulmonary hypertension.
AB  - BACKGROUND: Pulmonary hypertension (PH) is a severe disease with a poor
      prognosis. Different forms of PH are characterized by pronounced vascular
      remodeling, resulting in increased vascular resistance and subsequent right heart
      failure. The molecular pathways triggering the remodeling process are poorly
      understood. We hypothesized that underlying key factors can be identified at the
      onset of the disease. Thus, we screened for alterations to protein expression in
      lung tissue at the onset of PH in a mouse model of hypoxia-induced PH. METHODS
      AND RESULTS: Using 2-dimensional polyacrylamide gel electrophoresis in
      combination with matrix-assisted laser desorption/ionization time-of-flight
      analysis, we identified 36 proteins that exhibited significantly altered
      expression after short-term hypoxic exposure. Among these, Fhl-1, which is known
      to be involved in muscle development, was one of the most prominently upregulated
      proteins. Further analysis by immunohistochemistry, Western blot, and laser
      assisted microdissection followed by quantitative polymerase chain reaction
      confirmed the upregulation of Fhl-1, particularly in the pulmonary vasculature.
      Comparable upregulation was confirmed (1) after full establishment of hypoxia
      induced PH, (2) in 2 rat models of PH (monocrotaline-treated and hypoxic rats
      treated with the vascular endothelial growth factor receptor antagonist SU5416),
      and (3) in lungs from patients with idiopathic pulmonary arterial hypertension.
      Furthermore, we demonstrated that regulation of Fhl-1 was hypoxia-inducible
      transcription factor dependent. Abrogation of Fhl-1 expression in primary human
      pulmonary artery smooth muscle cells by small-interfering RNA suppressed, whereas
      Fhl-1 overexpression increased, migration and proliferation.
      Coimmunoprecipitation experiments identified Talin1 as a new interacting partner
      of Fhl-1. CONCLUSIONS: Protein screening identified Fhl-1 as a novel protein
      regulated in various forms of PH, including idiopathic pulmonary arterial
      hypertension.

PMID- 18725487
TI  - Dynamic mechanism for initiation of ventricular fibrillation in vivo.
AB  - BACKGROUND: Dynamically induced heterogeneities of repolarization may lead to
      wave-front destabilizations and initiation of ventricular fibrillation (VF). In a
      computer modeling study, we demonstrated that specific sequences of premature
      stimuli maximized dynamically induced spatial dispersion of refractoriness and
      predisposed the heart to the development of conduction block. The purpose of this
      study was to determine whether the computer model results pertained to the
      initiation of VF in dogs in vivo. METHODS AND RESULTS: Monophasic action
      potentials were recorded from right and left ventricular endocardium in
      anesthetized beagle dogs (n=11) in vivo. Restitution of action potential duration
      and conduction time and the effective refractory period after delivery of the
      basic stimulus (S(1)) and each of 3 premature stimuli (S(2), S(3), S(4)) were
      determined at baseline and during verapamil infusion. The effective refractory
      period data were used to determine the interstimulus intervals for a sequence of
      4 premature stimuli (S(2)S(3)S(4)S(5)=CL(VF)) for which the computer model
      predicted maximal spatial dispersion of refractoriness. Delivery of CL(VF) was
      associated with discordant action potential duration alternans and induction of
      VF in all dogs. Verapamil decreased spatial dispersion of refractoriness by
      reducing action potential duration and conduction time restitution in a dose
      dependent fashion, effects that were associated with reduced inducibility of VF
      with CL(VF). CONCLUSIONS: Maximizing dynamically induced spatial dispersion of
      repolarization appears to be an effective method for inducing VF. Reducing
      spatial dispersion of refractoriness by modulating restitution parameters can
      have an antifibrillatory effect in vivo.

PMID- 18725488
TI  - Incidence and prognostic implication of unrecognized myocardial scar
      characterized by cardiac magnetic resonance in diabetic patients without clinical
      evidence of myocardial infarction.
AB  - BACKGROUND: Silent myocardial infarctions (MIs) are prevalent among diabetic
      patients and inflict significant morbidity and mortality. Although late
      gadolinium enhancement (LGE) imaging by cardiac magnetic resonance (CMR) can
      provide sensitive characterization of myocardial scar, its prognostic
      significance in diabetic patients without any clinical evidence of MI is unknown.
      METHODS AND RESULTS: We performed clinically indicated CMR imaging in 187
      diabetic patients who were grouped by the absence (study group, n=109) or
      presence (control group, n=78) of clinical evidence of MI (clinical history of MI
      or Q waves on ECG). CMR imaging and follow-up were successful in 107 study
      patients (98%) and 74 control patients (95%). Cox regression analyses were
      performed to associate LGE with major adverse cardiovascular events (MACE),
      including death, acute MI, new congestive heart failure or unstable angina,
      stroke, and significant ventricular arrhythmias. LGE by CMR was present in 30 of
      107 study patients (28%). At a median follow-up of 17 months, 38 of 107 patients
      (36%) experienced MACE, which included 18 deaths. Presence of LGE was associated
      with a >3-fold hazards increase for MACE and for death (hazard ratio, 3.71 and
      3.61; P<0.001 and P=0.007, respectively). Adjusted to a model that combines
      patient age, sex, ST or T changes on ECG, and left ventricular end-systolic
      volume index, LGE maintained a >4-fold hazards increase for MACE (adjusted hazard
      ratio, 4.13; 95% confidence interval, 1.74 to 9.79; P=0.001). In addition, LGE
      provided significant prognostic value with MACE and with death adjusted to a
      diabetic-specific risk model for 5-year events. The presence of LGE was the
      strongest multivariable predictor of MACE and death by stepwise selection in the
      study patients. CONCLUSIONS: CMR imaging can characterize occult myocardial scar
      consistent with MI in diabetic patients without clinical evidence of MI. This
      imaging finding demonstrates strong association with MACE and mortality hazards
      that is incremental to clinical, ECG, and left ventricular function combined.

PMID- 18725489
TI  - Drug-eluting versus bare metal stents in patients with st-segment-elevation
      myocardial infarction: eight-month follow-up in the Drug Elution and Distal
      Protection in Acute Myocardial Infarction (DEDICATION) trial.
AB  - BACKGROUND: Implantation of drug-eluting stents (DES) limits the rate of coronary
      restenosis in most patients with coronary artery disease, but data are scarce
      with regard to their use in patients with ST-segment-elevation myocardial
      infarction and in connection with distal protection of the microvascular
      perfusion during primary percutaneous coronary intervention. METHODS AND RESULTS:
      We randomly assigned 626 patients referred within 12 hours from symptom onset of
      an ST-elevation myocardial infarction to have a DES or a bare metal stent
      implanted in the infarct-related lesion with or without distal protection during
      primary percutaneous coronary intervention. Quantitative coronary angiography was
      performed during the index treatment and 8 months later. The primary end point
      was loss of the lumen diameter in the infarct-related lesion induced by
      neointimal proliferation. Patients were comparable with regard to baseline
      demographic and angiographic characteristics. The mean late lumen loss was
      significantly lower in patients treated with a DES (0.06 mm; SD, 0.66 mm) than in
      patients who had a bare metal stent implanted (0.47 mm; SD, 0.69 mm; P<0.001).
      The rate of the composite end point of cardiac death, recurrent myocardial
      infarction, and target lesion revascularization was 8.6% in the DES group versus
      14.4% in the bare metal stent group (P=0.03). Cardiac death occurred in 4.2% and
      1.6% of the patients (P=0.09) and stent thrombosis occurred in 2.0% and 2.6%
      (P=0.72), respectively. CONCLUSIONS: Implantation of DES improves the
      angiographic outcome and need for repeat revascularization without increasing the
      short-term risk of stent thrombosis but has a tendency to increase cardiac death
      in patients with ST-segment-elevation myocardial infarction.

PMID- 18725490
TI  - Long-term safety and efficacy of percutaneous coronary intervention with stenting
      and coronary artery bypass surgery for multivessel coronary artery disease: a
      meta-analysis with 5-year patient-level data from the ARTS, ERACI-II, MASS-II,
      and SoS trials.
AB  - BACKGROUND: Randomized trials that studied clinical outcomes after percutaneous
      coronary intervention (PCI) with bare metal stenting versus coronary artery
      bypass grafting (CABG) are underpowered to properly assess safety end points like
      death, stroke, and myocardial infarction. Pooling data from randomized controlled
      trials increases the statistical power and allows better assessment of the
      treatment effect in high-risk subgroups. METHODS AND RESULTS: We performed a
      pooled analysis of 3051 patients in 4 randomized trials evaluating the relative
      safety and efficacy of PCI with stenting and CABG at 5 years for the treatment of
      multivessel coronary artery disease. The primary end point was the composite end
      point of death, stroke, or myocardial infarction. The secondary end point was the
      occurrence of major adverse cardiac and cerebrovascular accidents, death, stroke,
      myocardial infarction, and repeat revascularization. We tested for
      heterogeneities in treatment effect in patient subgroups. At 5 years, the
      cumulative incidence of death, myocardial infarction, and stroke was similar in
      patients randomized to PCI with stenting versus CABG (16.7% versus 16.9%,
      respectively; hazard ratio, 1.04, 95% confidence interval, 0.86 to 1.27; P=0.69).
      Repeat revascularization, however, occurred significantly more frequently after
      PCI than CABG (29.0% versus 7.9%, respectively; hazard ratio, 0.23; 95%
      confidence interval, 0.18 to 0.29; P<0.001). Major adverse cardiac and
      cerebrovascular events were significantly higher in the PCI than the CABG group
      (39.2% versus 23.0%, respectively; hazard ratio, 0.53; 95% confidence interval,
      0.45 to 0.61; P<0.001). No heterogeneity of treatment effect was found in the
      subgroups, including diabetic patients and those presenting with 3-vessel
      disease. CONCLUSIONS: In this pooled analysis of 4 randomized trials, PCI with
      stenting was associated with a long-term safety profile similar to that of CABG.
      However, as a result of persistently lower repeat revascularization rates in the
      CABG patients, overall major adverse cardiac and cerebrovascular event rates were
      significantly lower in the CABG group at 5 years.

PMID- 18725491
TI  - Longitudinal strain delay index by speckle tracking imaging: a new marker of
      response to cardiac resynchronization therapy.
AB  - BACKGROUND: In heart failure patients with left ventricular dyssynchrony,
      contractility in delayed segments does not fully contribute to end-systolic
      function. We quantified this reserve of contraction related to mechanical
      dyssynchrony to predict response to cardiac resynchronization therapy by the
      strain delay index, which was defined as the sum of the difference between peak
      and end-systolic strain across 16 segments. METHODS AND RESULTS: In 100 heart
      failure patients (ejection fraction=26+/-9%, QRS=154+/-29 ms, 94% in New York
      Heart Association class III), we studied left ventricular dyssynchrony before
      cardiac resynchronization therapy by the strain delay index using longitudinal
      strain by 2D speckle tracking and by the SD of time to peak myocardial velocity
      in 12 segments. The optimal cutoff value of the strain delay index to predict
      response to cardiac resynchronization therapy was determined in a retrospective
      group (n=65) and then confirmed in a validation group (n=35). Left ventricular
      end-systolic volume reduction at 3 months >15% (responder) occurred in 64 of 100
      patients. In the retrospective group, the strain delay index but not the SD of
      time to peak myocardial velocity was greater in responders (n=42/65) than
      nonresponders (35+/-8% versus 19+/-7%, P<0.0001), and the optimal cutoff value to
      identify response to cardiac resynchronization therapy was 25%. In the validation
      group, strain delay index > or =25% identified 82% (18/22) of responders and 92%
      (12/13) of nonresponders. Among the entire population (n=100), strain delay index
      correlated with reverse remodeling in both the ischemic (r=-0.68, P<0.0001) and
      nonischemic (r=-0.68, P<0.0001) population. CONCLUSIONS: Use of the strain delay
      index with longitudinal strain by speckle tracking has a strong predictive value
      for predicting response to cardiac resynchronization therapy in both ischemic and
      nonischemic patients.

PMID- 18725492
TI  - Public reporting of 30-day mortality for patients hospitalized with acute
      myocardial infarction and heart failure.

PMID- 18725493
TI  - Cardiology patient pages. How are our hospitals measuring up?: "hospital
      compare": a resource for hospital quality of care.

PMID- 18725494
TI  - Impact of in-hospital revascularization on survival in patients with non-ST
      elevation acute coronary syndrome and congestive heart failure.
AB  - BACKGROUND: Patients with non-ST-elevation acute coronary syndrome complicated by
      congestive heart failure (CHF) have a poor prognosis. The aims of this study were
      to describe the use of revascularization in non-ST-elevation acute coronary
      syndrome and CHF and to analyze its impact on survival. METHODS AND RESULTS: In
      the Global Registry of Acute Coronary Events, 29 844 patients with non-ST
      elevation acute coronary syndrome were enrolled at 120 hospitals in 14 countries
      between April 1999 and June 2007; 4953 had CHF at presentation. One fifth of the
      patients with CHF underwent revascularization versus 35% of those without CHF
      (P<0.001). Among CHF patients, revascularized patients had lower-risk baseline
      clinical characteristics than nonrevascularized patients and were more likely to
      receive evidence-based cardiac medications. Hospital rates were not affected by
      revascularization (adjusted hazard ratio 0.97, 95% confidence interval 0.72 to
      1.33, P=0.87). Death from discharge to 6-month follow-up was lower in patients
      who underwent revascularization than in those who did not (odds ratio 0.51, 95%
      confidence interval 0.35 to 0.74, P<0.001). This difference persisted after
      adjustment for GRACE risk score variables, country, and propensity for
      revascularization (odds ratio 0.58, 95% confidence interval 0.40 to 0.85,
      P=0.005). When revascularization as a time-varying covariate was taken into
      account in an adjusted Cox regression, the rate of death was again lower in
      patients undergoing revascularization (hazard ratio 0.64, 95% confidence interval
      0.45 to 0.93, P=0.02). CONCLUSIONS: This observational study suggests a low use
      of in-hospital revascularization in non-ST-elevation acute coronary syndrome
      patients with CHF. The consistent reduction in postdischarge death in
      revascularized patients suggests that broader application of revascularization in
      this high-risk group may be beneficial.

PMID- 18725495
TI  - Sleep apnea and cardiovascular disease: an American Heart Association/american
      College Of Cardiology Foundation Scientific Statement from the American Heart
      Association Council for High Blood Pressure Research Professional Education
      Committee, Council on Clinical Cardiology, Stroke Council, and Council On
      Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood
      Institute National Center on Sleep Disorders Research (National Institutes of
      Health).

PMID- 18725496
TI  - Images in cardiovascular medicine. Markedly dilated right heart 17 years after
      initial treatment repaired by total right ventricular exclusion and total
      cavopulmonary connection.

PMID- 18725497
TI  - Images in cardiovascular medicine. Placement of a left ventricular pacing lead
      after balloon angioplasty of a coronary vein stenosis: coronary sinus obstruction
      as a complication after mitral valve operation.

PMID- 18725498
TI  - Letter by Gasparrini and Gorini regarding article, "Effect of the Italian smoking
      ban on population rates of acute coronary events".

PMID- 18725500
TI  - Noninvasive assessment of cardiac electrophysiology for predicting arrhythmogenic
      risk: are we getting closer?

PMID- 18725501
TI  - Cardiac resynchronization therapy for heart failure: a hammer in search of nails.

PMID- 18725502
TI  - Primary prevention of stroke: impact of healthy lifestyle.

PMID- 18725503
TI  - Impaired tissue perfusion: a pathology common to hypertension, obesity, and
      diabetes mellitus.

PMID- 18725504
TI  - Images in cardiovascular medicine. Brugada-like ECG pattern in severe
      hypothermia.

PMID- 18725505
TI  - Identification of Ginkgo biloba as a novel activator of pregnane X receptor.
AB  - Pregnane X receptor (PXR; NR1I2) is a ligand-activated transcription factor that
      plays a role not only in drug metabolism and transport but also in various other
      biological processes. Ginkgo biloba is a herbal medicine commonly used to manage
      memory impairment. Treatment of primary cultures of rat hepatocytes with G.
      biloba extract increases the mRNA expression of CYP3A23, which is a target gene
      for rat PXR. The present study was conducted to test the hypothesis that G.
      biloba extract activates PXR. Treatment of mouse PXR (mPXR) or human PXR (hPXR)
      transfected HepG2 cells with G. biloba extract at 200 microg/ml increased mPXR
      and hPXR activation by 3.2- and 9.5-fold, respectively. Dose-response analysis
      showed a log-linear increase in hPXR activation by the extract over the range of
      200 to 800 microg/ml. To determine whether G. biloba extract induces hPXR target
      gene expression, cultured LS180 human colon adenocarcinoma cells were treated for
      72 h with the extract. G. biloba extract at 200, 400, and 800 microg/ml increased
      CYP3A4 mRNA expression by 1.7-, 2.4-, and 2.5-fold, respectively. The same
      concentrations of the extract increased CYP3A5 (1.3-3.6-fold) and P-glycoprotein
      (ABCB) 1 (2.7-6.4-fold) mRNA expression. At concentrations (5 and 10 microM) that
      did not down-regulate PXR gene expression and were not cytotoxic, L-sulforaphane
      (an hPXR antagonist) decreased CYP3A4, CYP3A5, and ABCB1 gene expression in cells
      treated with G. biloba extract. In summary, G. biloba extract activated mPXR and
      hPXR in a cell-based reporter gene assay and induced CYP3A4, CYP3A5, and ABCB1
      gene expression in hPXR-expressing LS180 cells.

PMID- 18725506
TI  - Intravenous formulation of N-hydroxy-N'-(4-n-butyl-2-methylphenyl)formamidine
      (HET0016) for inhibition of rat brain 20-hydroxyeicosatetraenoic acid formation.
AB  - N-hydroxy-N'-(4-n-butyl-2-methylphenyl)formamidine (HET0016) is a potent
      inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) formation by specific
      cytochrome P450 isoforms. Previous studies have demonstrated that administration
      of HET0016 inhibits brain formation of 20-HETE and reduces brain damage in a rat
      model of thromboembolic stroke. Delineation of the dose, concentration, and
      neuroprotective effect relationship of HET0016 has been hampered by the relative
      insolubility of HET0016 in aqueous solutions and the lack of information
      concerning the mechanism and duration of HET0016 inhibition of brain 20-HETE
      formation. Therefore, it was the purpose of this study to develop a water-soluble
      formulation of HET0016 suitable for intravenous (i.v.) administration and to
      determine the time course and mechanism of brain 20-HETE inhibition after in vivo
      dosing. In this study we report that HET0016 is a noncompetitive inhibitor of rat
      brain 20-HETE formation, which demonstrates a tissue concentration range for
      brain inhibition. In addition, we demonstrate that complexation of HET0016 with
      hydroxypropyl-beta-cyclodextrin results in increased aqueous solubility of
      HET0016 from 34.2 +/- 31.2 to 452.7 +/- 63.3 microg/ml. Administration of the
      complex as a single HET0016 i.v. dose (1 mg/kg) rapidly reduced rat brain 20-HETE
      concentrations from 289 to 91 pmol/g. Collectively, these data demonstrate that
      the i.v. formulation of HET0016 rapidly penetrates the rat brain and
      significantly inhibits 20-HETE tissue concentrations. These results will enable
      future studies to determine biopharmaceutics of HET0016 for inhibition of 20-HETE
      after cerebral ischemia.

PMID- 18725507
TI  - Modulation of cytochrome P450 gene expression and arachidonic acid metabolism
      during isoproterenol-induced cardiac hypertrophy in rats.
AB  - Several cytochrome P450 (P450) enzymes have been identified in the heart, and
      their levels have been reported to be altered during cardiac hypertrophy.
      Moreover, there is a strong correlation between P450-mediated arachidonic acid
      metabolites and the pathogenesis of cardiac hypertrophy. Therefore, we
      investigated the effect of isoproterenol-induced cardiac hypertrophy on the
      expression of several P450 genes and their associated P450-derived metabolites of
      arachidonic acid. Cardiac hypertrophy was induced by seven daily i.p. injections
      of 5 mg/kg isoproterenol. Thereafter, the heart, lung, liver, and kidney were
      harvested, and the expression of different genes was determined by real-time
      polymerase chain reaction. Heart microsomal protein from control or isoproterenol
      treated rats was incubated with 50 microM arachidonic acid, and arachidonic acid
      metabolites were determined by liquid chromatography-electron spray ionization
      mass spectrometry. Our results show that isoproterenol treatment significantly
      increased the heart/body weight ratio and the hypertrophic markers. In addition,
      there was a significant induction of CYP1A1, CYP1B1, CYP4A3, and soluble epoxide
      hydrolase and a significant inhibition of CYP2C11 and CYP2E1 in the hypertrophied
      hearts as compared with the control. CYP1A1, CYP2E1, and CYP4A3 gene expression
      was induced in the kidney, and CYP4A3 was induced in the liver of isoproterenol
      treated rats. Isoproterenol treatment significantly reduced 5,6-, 8,9-, 11,12-,
      and 14,15-epoxyeicosatrienoic acid formation and significantly increased their
      corresponding 8,9-, and 14,15-dihydroxyeicosatrienoic acid and the 20
      hydroxyeicosatetraenoic acid metabolite. In conclusion, isoproterenol-induced
      cardiac hypertrophy alters arachidonic acid metabolism and its associated P450
      enzymes, suggesting their role in the development and/or progression of cardiac
      hypertrophy.

PMID- 18725508
TI  - Identification of hydroxywarfarin binding site in human UDP
      glucuronosyltransferase 1a10: phenylalanine90 is crucial for the glucuronidation
      of 6- and 7-hydroxywarfarin but not 8-hydroxywarfarin.
AB  - Recent studies show that the extrahepatic human UDP-glucuronosyltransferase
      (UGT)1A10 is capable of phase II glucuronidation of several major cytochrome P450
      metabolites of warfarin (i.e., 6-, 7-, and 8-hydroxywarfarin). This study expands
      on this finding by testing the hypothesis that the UGT1A10 F(90)-M(91)-V(92)
      F(93) amino acid motif is important for proper recognition and conjugation of
      hydroxywarfarin derivatives. Site-directed mutagenesis studies demonstrate that
      F(90) is critical for 6- and 7-hydroxywarfarin glucuronidation based on the
      complete loss of enzymatic activity toward these substrates. In contrast, V92A
      and F93A mutants lead to higher rates of substrate turnover, have minimum changes
      in K(m) values, and demonstrate substrate inhibition kinetics. A completely
      different activity profile is observed in the presence of 8-hydroxywarfarin. No
      change in either activity or affinity is observed with F90A when compared with
      wild type, whereas F93A and V92A mutants show increases in V(max) (3- and 10
      fold, respectively) and minimum changes in K(m). Liquid chromatographytandem mass
      spectrometry studies show that enzymatic products produced by mutants are
      identical to wild-type products produced in the presence of 6-, 7-, and 8
      hydroxywarfarin. Because F(90) is not critical for the glucuronidation of 8
      hydroxywarfarin, there is likely another, different amino acid responsible for
      binding this compound. In addition, an inhibitory binding site may be formed in
      the presence of 6- and 7-hydroxywarfarin. This new knowledge and continued
      characterization of the hydroxywarfarin binding site(s) for UGT1A10 will help
      elucidate the molecular mechanism of hydroxywarfarin glucuronidation and
      potentially result in more effective anticoagulant therapies.

PMID- 18725509
TI  - Metabolic profiling and cytochrome P450 reaction phenotyping of
      medroxyprogesterone acetate.
AB  - Medroxyprogesterone acetate (MPA) is one of the most frequently prescribed
      progestins for conception, hormone replacement therapy, and adjuvant endocrine
      therapy. MPA has a low oral bioavailability because of extensive metabolism;
      however, its metabolism was poorly documented. This study was intended to profile
      the phase I metabolites of MPA and the cytochrome P450 (P450) isoforms involved.
      After MPA was incubated with human liver microsomes and the NADPH-generating
      system, five main metabolites (namely M-1, M-2, M-3, M-4, and M-5) were isolated
      by high-performance liquid chromatography. Three major metabolites (M-2, M-4, and
      M-3) were tentatively identified to be 6beta-, 2beta-, and 1beta-hydroxy MPA by
      liquid chromatography/mass spectrometry and (1)H nuclear magnetic resonance. By
      consecutive metabolism of purified M-2, M-3, and M-4, M-1 and M-5 were proposed
      to be 2beta-, 6beta-dihydroxy MPA, and 1,2-dehydro MPA, respectively. CYP3A4 was
      identified to be the isoform primarily involved in the formation of M-2, M-3, and
      M-4 in studies with specific P450 inhibitors, recombinant P450s, and correlation
      analysis. Rat and minipig liver microsomes were included evaluating species
      differences, and the results showed little difference among the species. In human
      liver microsomes, the K(m) values ranged from 10.0 to 11.2 muM, and the V(m)
      values ranged from 194 to 437 pmol/min/mg for M-2, M-3, and M-4. In conclusion,
      CYP3A4 was the major P450 isoform involved in MPA hydroxylation, with 6beta,
      2beta, and 1beta being the possible hydroxylation sites. Minipig and rat could be
      the surrogate models for man in MPA pharmacokinetic studies.

PMID- 18725510
TI  - The molecular basis of CYP2D6-mediated N-dealkylation: balance between metabolic
      clearance routes and enzyme inhibition.
AB  - N-dealkylation is a commonly observed metabolic reaction for drugs containing
      secondary and tertiary amines. On searching the literature, it is obvious that
      this reaction is far less common among cytochrome P450 2D6 catalyzed reactions
      compared with other cytochromes P450. The CYP2D6 pharmacophore and characteristic
      features in the active site cavity suggest a favored substrate orientation that
      prevents N-dealkylation from occurring. In this study, the literature was
      searched for N-dealkylated and non-N-dealkylated CYP2D6 substrates. The
      hypothesis that was suggested and confirmed demonstrated that N-dealkylation
      occurs by this enzyme when the preferred site of metabolism is blocked toward
      other oxidative metabolic pathways. An interesting observation was also that
      addition of stable groups at preferred sites of metabolism generally improved the
      metabolic stability but also resulted in retained or increased inhibition of the
      enzyme. In addition, the effect of pH on N- and O-dealkylation of
      dextromethorphan was shown to be consistent with the hypothesis that an ionized
      amino function favored substrate dockings resulting in O-dealkylation.

PMID- 18725511
TI  - The role of human hepatic cytochrome P450 isozymes in the metabolism of racemic
      3,4-methylenedioxy-methamphetamine and its enantiomers.
AB  - The entactogen, 3,4-methylenedioxy-methamphetamine (MDMA), is a chiral drug that
      is mainly metabolized by N-demethylation and demethylenation. The involvement of
      cytochrome P450 (P450) isozymes in these metabolic steps has been studied by
      inhibition assays with human liver microsomes and, in part, with heterologously
      expressed human P450 isozymes. However, a comprehensive study on the involvement
      of all relevant human P450s has not been published yet. In addition, the
      chirality of this drug was not considered in these in vitro studies. The aim of
      the present work was to study the contribution of human P450 isozymes in the N
      demethylation and demethylenation of racemic MDMA and its single enantiomers.
      MDMA and its enantiomers were incubated using heterologously expressed human
      P450s, and the metabolites were quantified by gas chromatography-mass
      spectrometry after derivatization with S-heptafluorobutyrylprolyl chloride. The
      highest contribution for the N-demethylation as calculated from the enzyme
      kinetic data, were obtained for CYP2B6 (R,S-MDMA), CYP1A2 (R-MDMA), and CYP2B6 (S
      MDMA). In the case of the demethylenation, the isozyme with the highest
      contribution to net clearance for R,S-MDMA, R-MDMA, and S-MDMA was CYP2D6. For
      the first time, marked enantioselectivity was observed for N-demethylation and
      demethylenation by CYP2C19 with a preference for the S-enantiomers. In addition,
      CYP2D6 showed preference for S-MDMA in the case of demethylenation. None of the
      other isozymes showed major preferences for certain enantiomers. In conclusion,
      therefore, the different pharmacokinetic properties of the MDMA enantiomers may
      be caused by enantioselective metabolism by CYP2C19 and CYP2D6.

PMID- 18725512
TI  - Physical activity in relation to total, advanced, and fatal prostate cancer.
AB  - Physical activity has been inconsistently related to total prostate cancer and
      few studies have examined whether this association varies by disease
      aggressiveness. We examined physical activity in relation to total, advanced, and
      fatal prostate cancer in the NIH-AARP Diet and Health Study. At baseline (1995
      1996), 293,902 men ages 50 to 71 years completed a questionnaire inquiring about
      current frequency of vigorous exercise of at least 20 min of duration, as well as
      frequency of exercise during adolescence (ages 15-18). We used proportional
      hazards regression to calculate multivariate relative risks (RR) and 95%
      confidence intervals (95% CI). During up to 8.2 years of follow-up, 17,872
      prostate cancer cases were identified, including 1,942 advanced and 513 fatal
      cases. Comparing frequent (5+ times per week) versus infrequent (less than once
      per week) vigorous exercise, exercise at baseline was not associated with risk of
      total prostate cancer (RR, 1.01; 95% CI, 0.96-1.07; P(trend) = 0.78), advanced
      prostate cancer (RR, 1.14; 95% CI, 0.97-1.33; P(trend) = 0.25), or fatal prostate
      cancer (RR, 0.90; 95% CI, 0.67-1.20; P(trend) = 0.12). Increasing level of
      vigorous exercise during adolescence was associated with a small 3% reduction in
      total prostate cancer risk (frequent versus infrequent exercise during
      adolescence: RR, 0.97; 95% CI, 0.91-1.03; P(trend) = 0.03) but was not associated
      with risk of advanced prostate cancer (RR, 0.95; 95% CI, 0.78-1.14; P(trend) =
      0.18) or fatal prostate cancer (RR, 0.96; 95% CI, 0.67-1.36; P(trend) = 0.99).
      Neither vigorous exercise at baseline nor exercise during adolescence was related
      to risk of total, advanced, or fatal prostate cancer in this large prospective
      cohort.

PMID- 18725513
TI  - Estrogen plus progestin and risk of benign proliferative breast disease.
AB  - Women with benign proliferative breast disease are at increased risk of
      subsequent breast cancer. Estrogens and progesterone exert proliferative effects
      on mammary epithelium, and combined hormone replacement therapy has been
      associated with increased breast cancer risk. We tested the effect of conjugated
      equine estrogen plus progestin on the risk of benign proliferative breast disease
      in the Women's Health Initiative (WHI) randomized controlled trial. In the WHI
      trial of estrogen plus progestin, 16,608 postmenopausal women were randomly
      assigned either to 0.625 mg/day of conjugated equine estrogen plus 2.5 mg/day of
      medroxyprogesterone acetate or to placebo. Baseline and annual breast exams and
      mammograms were required. The trial was terminated early (average follow-up, 5.5
      years). We identified women who had had a biopsy for benign breast disease, and
      subjected histologic sections from the biopsies to standardized review. Overall,
      178 incident cases of benign proliferative breast disease were ascertained in the
      estrogen plus progestin group and 99 in the placebo group. The use of estrogen
      plus progestin was associated with a 74% increase in the risk of benign
      proliferative breast disease [hazard ratio, 1.74; 95% confidence interval (CI),
      1.35-2.25]. For benign proliferative breast disease without atypia the hazard
      ratio was 2.00 (95% CI, 1.50-2.66), while for atypical hyperplasia it was 0.76
      (95% CI, 0.38-1.52). The risk varied little by levels of baseline
      characteristics. The results of this study suggest that the use of estrogen plus
      progestin may increase the risk of benign proliferative breast disease.

PMID- 18725514
TI  - On the trail of the 'new head' in Les Treilles.
AB  - The vertebrate brain develops in association with neighboring tissues: neural
      crest, placodes, mesoderm and endoderm. The molecular and evolutionary
      relationships between the forming nervous system and the other craniofacial
      structures were at the focus of a recent meeting at the Fondation des Treilles in
      France. Entitled 'Relationships between Craniofacial and Neural Development', the
      meeting brought together researchers working on diverse species, the findings of
      whom provide clues as to the origin and diversity of the brain and facial regions
      that are involved in forming the 'new head' of vertebrates.

PMID- 18725515
TI  - Distinct sequential cell behaviours direct primitive endoderm formation in the
      mouse blastocyst.
AB  - The first two lineages to differentiate from a pluripotent cell population during
      mammalian development are the extraembryonic trophectoderm (TE) and the primitive
      endoderm (PrE). Whereas the mechanisms of TE specification have been extensively
      studied, segregation of PrE and the pluripotent epiblast (EPI) has received
      comparatively little attention. A current model of PrE specification suggests PrE
      precursors exhibit an apparently random distribution within the inner cell mass
      of the early blastocyst and then segregate to their final position lining the
      cavity by the late blastocyst. We have identified platelet-derived growth factor
      receptor alpha (Pdgfralpha) as an early-expressed protein that is also a marker
      of the later PrE lineage. By combining live imaging of embryos expressing a
      histone H2B-GFP fusion protein reporter under the control of Pdgfra regulatory
      elements with the analysis of lineage-specific markers, we investigated the
      events leading to PrE and EPI lineage segregation in the mouse, and correlated
      our findings using an embryo staging system based on total cell number. Before
      blastocyst formation, lineage-specific factors are expressed in an overlapping
      manner. Subsequently, a gradual progression towards a mutually exclusive
      expression of PrE- and EPI-specific markers occurs. Finally, cell sorting is
      achieved by a variety of cell behaviours and by selective apoptosis.

PMID- 18725516
TI  - Single-cell gene profiling defines differential progenitor subclasses in
      mammalian neurogenesis.
AB  - Cellular diversity of the brain is largely attributed to the spatial and temporal
      heterogeneity of progenitor cells. In mammalian cerebral development, it has been
      difficult to determine how heterogeneous the neural progenitor cells are, owing
      to dynamic changes in their nuclear position and gene expression. To address this
      issue, we systematically analyzed the cDNA profiles of a large number of single
      progenitor cells at the mid-embryonic stage in mouse. By cluster analysis and in
      situ hybridization, we have identified a set of genes that distinguishes between
      the apical and basal progenitors. Despite their relatively homogeneous global
      gene expression profiles, the apical progenitors exhibit highly variable
      expression patterns of Notch signaling components, raising the possibility that
      this causes the heterogeneous division patterns of these cells. Furthermore, we
      successfully captured the nascent state of basal progenitor cells. These cells
      are generated shortly after birth from the division of the apical progenitors,
      and show strong expression of the major Notch ligand delta-like 1, which soon
      fades away as the cells migrate in the ventricular zone. We also demonstrated
      that attenuation of Notch signals immediately induces differentiation of apical
      progenitors into nascent basal progenitors. Thus, a Notch-dependent feedback loop
      is likely to be in operation to maintain both progenitor populations.

PMID- 18725517
TI  - A crucial role for hnRNP K in axon development in Xenopus laevis.
AB  - We report that hnRNP K, an RNA-binding protein implicated in multiple aspects of
      post-transcriptional gene control, is essential for axon outgrowth in Xenopus.
      Its intracellular localization was found to be consistent with one of its known
      roles as an mRNA shuttling protein. In early embryos, it was primarily nuclear,
      whereas later it occupied both the nucleus and cytoplasm to varying degrees in
      different neuronal subtypes. Antisense hnRNP K morpholino oligonucleotides (MOs)
      microinjected into blastomeres suppressed hnRNP K expression from neural plate
      stages through to at least stage 40. Differentiating neural cells in these
      embryos expressed several markers for terminally differentiated neurons but
      failed to make axons. Rescue experiments and the use of two separate hnRNP K MOs
      were carried out to confirm that these effects were specifically caused by
      knockdown of hnRNP K expression. For insights into the involvement of hnRNP K in
      neuronal post-transcriptional gene control at the molecular level, we compared
      effects on expression of the medium neurofilament protein (NF-M), the RNA for
      which binds hnRNP K, with that of peripherin, another intermediate filament
      protein, the RNA for which does not bind hnRNP K. hnRNP K knockdown compromised
      NF-M mRNA nucleocytoplasmic export and translation, but had no effect on
      peripherin. Because eliminating NF-M from Xenopus axons attenuates, but does not
      abolish, their outgrowth, hnRNP K must target additional RNAs needed for axon
      development. Our study supports the idea that translation of at least a subset of
      RNAs involved in axon development is controlled by post-transcriptional
      regulatory modules that have hnRNP K as an essential element.

PMID- 18725518
TI  - Gsk3beta/PKA and Gli1 regulate the maintenance of neural progenitors at the
      midbrain-hindbrain boundary in concert with E(Spl) factor activity.
AB  - Neuronal production in the midbrain-hindbrain domain (MH) of the vertebrate
      embryonic neural tube depends on a progenitor pool called the ;intervening zone'
      (IZ), located at the midbrain-hindbrain boundary. The progressive recruitment of
      IZ progenitors along the mediolateral (future dorsoventral) axis prefigures the
      earlier maturation of the MH basal plate. It also correlates with a lower
      sensitivity of medial versus lateral IZ progenitors to the neurogenesis
      inhibition process that maintains the IZ pool. This role is performed in
      zebrafish by the E(Spl) factors Her5 and Her11, but the molecular cascades
      cooperating with Her5/11, and those accounting for their reduced effect in the
      medial IZ, remain unknown. We demonstrate here that the kinases Gsk3beta and cAMP
      dependent protein kinase A (PKA) are novel determinants of IZ formation and
      cooperate with E(Spl) activity in a dose-dependent manner. Similar to E(Spl), we
      show that the activity of Gsk3beta/PKA is sensed differently by medial versus
      lateral IZ progenitors. Furthermore, we identify the transcription factor Gli1,
      expressed in medial IZ cells, as an antagonist of E(Spl) and Gsk3beta/PKA, and
      demonstrate that the neurogenesis-promoting activity of Gli1 accounts for the
      reduced sensitivity of medial IZ progenitors to neurogenesis inhibitors and their
      increased propensity to differentiate. We also show that the expression and
      activity of Gli1 in this process are, surprisingly, independent of Hedgehog
      signaling. Together, our results suggest a model in which the modulation of
      E(Spl) and Gsk3beta/PKA activities by Gli1 underlies the dynamic properties of IZ
      maintenance and recruitment.

PMID- 18725519
TI  - Hedgehog signaling to distinct cell types differentially regulates coronary
      artery and vein development.
AB  - Vascular development begins with formation of a primary capillary plexus that is
      later remodeled to give rise to the definitive vasculature. Although the
      mechanism by which arterial and venous fates are acquired is well understood,
      little is known about when during vascular development arterial and venous
      vessels emerge and how their growth is regulated. Previously, we have
      demonstrated that a hedgehog (HH)/vascular endothelial growth factor (VEGF) and
      angiopoeitin 2 (ANG2) signaling pathway is essential for the development of the
      coronary vasculature. Here, we use conditional gene targeting to identify the
      cell types that receive HH signaling and mediate coronary vascular development.
      We show that HH signaling to the cardiomyoblast is required for the development
      of coronary veins, while HH signaling to the perivascular cell (PVC) is necessary
      for coronary arterial growth. Moreover, the cardiomyoblast and PVC appear to be
      the exclusive cell types that receive HH signals, as ablation of HH signaling in
      both cell types leads to an arrest in coronary development. Finally, we present
      evidence suggesting that coronary arteries and veins may be derived from distinct
      lineages.

PMID- 18725521
TI  - Stimulation of Toll-like receptor 3 and 4 induces interleukin-1beta maturation by
      caspase-8.
AB  - The cytokine interleukin (IL)-1beta is a key mediator of the inflammatory
      response and has been implicated in the pathophysiology of acute and chronic
      inflammation. IL-1beta is synthesized in response to many stimuli as an inactive
      pro-IL-1beta precursor protein that is further processed by caspase-1 into mature
      IL-1beta, which is the secreted biologically active form of the cytokine.
      Although stimulation of membrane-bound Toll-like receptors (TLRs) up-regulates
      pro-IL-1beta expression, activation of caspase-1 is believed to be mainly
      initiated by cytosolic Nod-like receptors. In this study, we show that
      polyinosinic:polycytidylic acid (poly[I:C]) and lipopolysaccharide stimulation of
      macrophages induces pro-IL-1beta processing via a Toll/IL-1R domain-containing
      adaptor-inducing interferon-beta-dependent signaling pathway that is initiated by
      TLR3 and TLR4, respectively. Ribonucleic acid interference (RNAi)-mediated
      knockdown of the intracellular receptors NALP3 or MDA5 did not affect poly(I:C)
      induced pro-IL-1beta processing. Surprisingly, poly(I:C)- and LPS-induced pro-IL
      1beta processing still occurred in caspase-1-deficient cells. In contrast, pro-IL
      1beta processing was inhibited by caspase-8 peptide inhibitors, CrmA or vFLIP
      expression, and caspase-8 knockdown via RNAi, indicating an essential role for
      caspase-8. Moreover, recombinant caspase-8 was able to cleave pro-IL-1beta in
      vitro at exactly the same site as caspase-1. These results implicate a novel role
      for caspase-8 in the production of biologically active IL-1beta in response to
      TLR3 and TLR4 stimulation.

PMID- 18725520
TI  - Toll-like receptor and IL-12 signaling control susceptibility to contact
      hypersensitivity.
AB  - Allergic contact hypersensitivity (CHS) is a T cell-mediated inflammatory skin
      disease. Interleukin (IL)-12 is considered to be important in the generation of
      the allergen-specific T cell response. Loss of IL-12 function in IL-12Rbeta2
      deficient mice, however, did not ameliorate the allergic immune response,
      suggesting alternate IL-12-independent pathways in the induction of CHS. Because
      exposure to contact allergens always takes place in the presence of microbial
      skin flora, we investigated the potential role of Toll-like receptors (TLRs) in
      the induction of CHS. Using mice deficient in TLR4, the receptor for bacterial
      lipopolysaccharide (LPS), IL-12 receptor (R) beta2, or both, we show that the
      concomitant absence of TLR4 and IL-12Rbeta2, but not the absence of TLR4 or IL
      12Rbeta2 alone, prevented DC-mediated sensitization, generation of effector T
      cells, and the subsequent CHS response to 2,4,6-trinitro-1-chlorobenzene (TNCB),
      oxazolone, and fluorescein isothiocyanate. Introduction of the TLR4 transgene
      into the TLR4/IL-12Rbeta2 mutant restored the CHS inducibility, showing a
      requirement for TLR4 in IL-12-independent CHS induction. Furthermore, the
      concomitant absence of TLR2 and TLR4 prevented the induction of CHS to TNCB in IL
      12-competent mice. Finally, CHS was inducible in germ-free wild-type and IL
      12Rbeta2-deficient mice, but not in germ-free TLR4/IL-12Rbeta2 double deficient
      mice, suggesting that the necessary TLR activation may proceed via endogenous
      ligands.

PMID- 18725522
TI  - Limited tumor infiltration by activated T effector cells restricts the
      therapeutic activity of regulatory T cell depletion against established melanoma.
AB  - Interference with inhibitory immunological checkpoints controlling T cell
      activation provides new opportunities to augment cancer immunotherapies. Whereas
      cytotoxic T lymphocyte-associated antigen-4 blockade has shown promising
      preclinical and clinical results, therapeutic CD4(+)CD25(+) T reg cell depletion
      has failed to consistently enhance immune-based therapies. Using B16/BL6, a
      transplantable murine melanoma model, we show a dichotomy between the effects of
      T reg cell depletion on tumor rejection dependent on whether depletion occurs
      before (prophylactic) or after (therapeutic) tumor engraftment. Failure to
      promote rejection with therapeutic depletion is not related to lack of T reg cell
      depletion, to elimination of CD25(+) effector T cells, or to a failure to enhance
      systemic antitumor T cell responses, but correlates with failure of effector
      cells to infiltrate the tumor and increase the intratumor ratio of effector T
      cell/T reg cell. Finally, systemic antitumor responses generated upon therapeutic
      T reg cell depletion are significantly stronger than those generated in the
      presence of T reg cells, and are capable of eliciting rejection of established
      tumors after transfer into immunoablated recipients receiving combination
      immunotherapy. The data demonstrate a dissociation between measurable systemic
      responses and tumor rejection during CD25-directed T reg cell depletion, and
      suggest an alternative, clinically applicable strategy for the treatment of
      established tumors.

PMID- 18725523
TI  - Blimp-1 directly represses Il2 and the Il2 activator Fos, attenuating T cell
      proliferation and survival.
AB  - Mice with a T cell-specific deletion of Prdm1, encoding Blimp-1, have aberrant T
      cell homeostasis and develop fatal colitis. In this study, we show that one
      critical activity of Blimp-1 in T cells is to repress IL-2, and that it does so
      by direct repression of Il2 transcription, and also by repression of Fos
      transcription. Using these mechanisms Blimp-1 participates in an autoregulatory
      loop by which IL-2 induces Prdm1 expression and thus represses its own expression
      after T cell activation, ensuring that the immune response is appropriately
      controlled. This activity of Blimp-1 is important for cytokine deprivation
      induced T cell death and for attenuating T cell proliferation in antigen-specific
      responses both in vitro and in vivo.

PMID- 18725524
TI  - A critical role for Apc in hematopoietic stem and progenitor cell survival.
AB  - The adenomatous polyposis coli (Apc) tumor suppressor is involved in the
      initiation and progression of colorectal cancer via regulation of the Wnt
      signaling cascade. In addition, Apc plays an important role in multiple cellular
      functions, including cell migration and adhesion, spindle assembly, and
      chromosome segregation. However, its role during adult hematopoiesis is unknown.
      We show that conditional inactivation of Apc in vivo dramatically increases
      apoptosis and enhances cell cycle entry of hematopoietic stem cells (HSCs)/
      hematopoietic progenitor cells (HPCs), leading to their rapid disappearance and
      bone marrow failure. The defect in HSCs/HPCs caused by Apc ablation is cell
      autonomous. In addition, we found that loss of Apc leads to exhaustion of the
      myeloid progenitor pool (common myeloid progenitor, granulocyte-monocyte
      progenitor, and megakaryocyte-erythroid progenitor), as well as the lymphoid
      primed multipotent progenitor pool. Down-regulation of the genes encoding Cdkn1a,
      Cdkn1b, and Mcl1 occurs after acute Apc excision in candidate HSC populations.
      Together, our data demonstrate that Apc is essential for HSC and HPC maintenance
      and survival.

PMID- 18725525
TI  - Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity.
AB  - A new regulatory T (T reg) cell-specific, FoxP3-GFP-hCre bacterial artificial
      chromosome transgenic mouse was crossed to a conditional Dicer knockout (KO)
      mouse strain to analyze the role of microRNAs (miRNAs) in the development and
      function of T reg cells. Although thymic T reg cells developed normally in this
      setting, the cells showed evidence of altered differentiation and dysfunction in
      the periphery. Dicer-deficient T reg lineage cells failed to remain stable, as a
      subset of cells down-regulated the T reg cell-specific transcription factor
      FoxP3, whereas the majority expressed altered levels of multiple genes and
      proteins (including Neuropilin 1, glucocorticoid-induced tumor necrosis factor
      receptor, and cytotoxic T lymphocyte antigen 4) associated with the T reg cell
      fingerprint. In fact, a significant percentage of the T reg lineage cells took on
      a T helper cell memory phenotype including increased levels of CD127, interleukin
      4, and interferon gamma. Importantly, Dicer-deficient T reg cells lost
      suppression activity in vivo; the mice rapidly developed fatal systemic
      autoimmune disease resembling the FoxP3 KO phenotype. These results support a
      central role for miRNAs in maintaining the stability of differentiated T reg cell
      function in vivo and homeostasis of the adaptive immune system.

PMID- 18725526
TI  - Dicer-dependent microRNA pathway safeguards regulatory T cell function.
AB  - Regulatory T (T reg) cells are indispensable for preventing autoimmunity.
      Incumbent to this role is the ability of T reg cells to exert their suppressor
      function under inflammatory conditions. We found that T reg cell-mediated
      tolerance is critically dependent on the Dicer-controlled microRNA (miRNA)
      pathway. Depletion of miRNA within the T reg cell lineage resulted in fatal
      autoimmunity indistinguishable from that in T reg cell-deficient mice. In disease
      free mice lacking Dicer in all T cells or harboring both Dicer-deficient and 
      sufficient T reg cells, Dicer-deficient T reg cells were suppressive, albeit to a
      lesser degree, whereas their homeostatic potential was diminished as compared
      with their Dicer-sufficient counterparts. However, in diseased mice, Dicer
      deficient T reg cells completely lost suppressor capacity. Thus, miRNA preserve
      the T reg cell functional program under inflammatory conditions.

PMID- 18725527
TI  - The RNAseIII enzyme Drosha is critical in T cells for preventing lethal
      inflammatory disease.
AB  - MicroRNAs (miRNAs) are implicated in the differentiation and function of many
      cell types. We provide genetic and in vivo evidence that the two RNaseIII
      enzymes, Drosha and Dicer, do indeed function in the same pathway. These have
      previously been shown to mediate the stepwise maturation of miRNAs (Lee, Y., C.
      Ahn, J. Han, H. Choi, J. Kim, J. Yim, J. Lee, P. Provost, O. Radmark, S. Kim, and
      V.N. Kim. 2003. Nature. 425:415-419), and genetic ablation of either within the T
      cell compartment, or specifically within Foxp3(+) regulatory T (T reg) cells,
      results in identical phenotypes. We found that miRNA biogenesis is indispensable
      for the function of T reg cells. Specific deletion of either Drosha or Dicer
      phenocopies mice lacking a functional Foxp3 gene or Foxp3(+) cells, whereas
      deletion throughout the T cell compartment also results in spontaneous
      inflammatory disease, but later in life. Thus, miRNA-dependent regulation is
      critical for preventing spontaneous inflammation and autoimmunity.

PMID- 18725529
TI  - Nitric oxide-mediated modulation of synaptic activity by astrocytic P2Y
      receptors.
AB  - We investigated the mechanism of synaptic suppression by P2Y receptors in mixed
      hippocampal cultures wherein networked neurons exhibit synchronized Ca(2+)
      oscillations (SCO) due to spontaneous glutamatergic synaptic transmission.
      Pharmacological studies suggested that SCO suppression was mediated by P2Y2/P2Y4
      receptors. Immunostaining studies and characterization of ATP/UTP-stimulated
      Ca(2+) responses in solitary neurons and astrocytes revealed that the SCO
      attenuation was effectuated by astrocytes. We demonstrate that nitric oxide
      released from activated astrocytes causes synaptic suppression by inhibiting
      neurotransmitter release. Physiological concentrations of ATP and UTP evoked NO
      production in astrocytes. SCO suppression was considerably diminished by removal
      of extracellular NO by membrane-impermeable scavenger c-PTIO or by pretreatment
      of cells with nitric oxide synthase inhibitor L-NAME. The nitric oxide donor
      DETA/NO effectively suppressed the SCO. ATP/UTP inhibited KCl-induced exocytosis
      at presynaptic terminals in an NO-dependent manner. In the absence of exogenously
      added ATP/UTP, both the NO scavenger and NOS inhibitor enhanced the frequency of
      SCO, implying that astrocytes release NO during spontaneous synaptic activity and
      exert a suppressive effect. We report for the first time that under physiological
      conditions astrocytes use NO as a messenger molecule to modulate the synaptic
      strength in the networked neurons.

PMID- 18725530
TI  - Preventing voltage-dependent gating of anthrax toxin channels using engineered
      disulfides.
AB  - The channel-forming component of anthrax toxin, (PA(63))(7), is a heptameric
      water-soluble protein at neutral pH, but under acidic conditions it spontaneously
      inserts into lipid bilayers to form a 14-stranded beta-barrel ion-conducting
      channel. This channel plays a vital role in anthrax pathogenesis because it
      serves as a conduit for the membrane translocation of the two enzymatic
      components of anthrax toxin, lethal factor and edema factor. Anthrax channels
      open and close in response to changes in transmembrane voltage, a property shared
      by several other pore-forming toxins. We have discovered an unexpected phenomenon
      in cysteine-substituted channels that provides a window into this gating process:
      their normal voltage-dependent gating can be abolished by reaction with
      methanethiosulfonate (MTS) reagents or exposure to oxidizing conditions.
      Remarkably, this perturbation is seen with cysteines substituted at sites all
      along the approximately 100 A length of the channel's beta-barrel. In contrast,
      reaction with N-ethylmaleimide, a thiol-reactive compound that does not form a
      mixed disulfide, does not affect gating at any of the sites tested. These
      findings, coupled with our biochemical detection of dimers, have led us to
      conclude that MTS reagents are catalyzing the formation of intersubunit disulfide
      bonds that lock channels in a conducting state, and that voltage gating requires
      a conformational change that involves the entire beta-barrel.

PMID- 18725531
TI  - A carboxy-terminal inter-helix linker as the site of phosphatidylinositol 4,5
      bisphosphate action on Kv7 (M-type) K+ channels.
AB  - The regulation of M-type (KCNQ [Kv7]) K(+) channels by phosphatidylinositol 4,5
      bisphosphate (PIP(2)) has perhaps the best correspondence to physiological
      signaling, but the site of action and structural motif of PIP(2) on these
      channels have not been established. Using single-channel recordings of chimeras
      of Kv7.3 and 7.4 channels with highly differential PIP(2) sensitivities, we
      localized a carboxy-terminal inter-helix linker as the primary site of PIP(2)
      action. Point mutants within this linker in Kv7.2 and Kv7.3 identified a
      conserved cluster of basic residues that interact with the lipid using
      electrostatic and hydrogen bonds. Homology modeling of this putative PIP(2)
      binding linker in Kv7.2 and Kv7.3 using the solved structure of Kir2.1 and Kir3.1
      channels as templates predicts a structure of Kv7.2 and 7.3 very similar to the
      Kir channels, and to the seven-beta-sheet barrel motif common to other PIP(2)
      binding domains. Phosphoinositide-docking simulations predict affinities and
      interaction energies in accord with the experimental data, and furthermore
      indicate that the precise identity of residues in the interacting pocket alter
      channel-PIP(2) interactions not only by altering electrostatic energies, but also
      by allosterically shifting the structure of the lipid-binding surface. The
      results are likely to shed light on the general structural mechanisms of
      phosphoinositide regulation of ion channels.

PMID- 18725532
TI  - Mutations of nonconserved residues within the calcium channel alpha1-interaction
      domain inhibit beta-subunit potentiation.
AB  - Voltage-dependent calcium channels consist of a pore-forming subunit
      (Ca(V)alpha(1)) that includes all the molecular determinants of a voltage-gated
      channel, and several accessory subunits. The ancillary beta-subunit (Ca(V)beta)
      is a potent activator of voltage-dependent calcium channels, but the mechanisms
      and structural bases of this regulation remain elusive. Ca(V)beta binds
      reversibly to a conserved consensus sequence in Ca(V)alpha(1), the alpha(1)
      interaction domain (AID), which forms an alpha-helix when complexed with
      Ca(V)beta. Conserved aromatic residues face to one side of the helix and strongly
      interact with a hydrophobic pocket on Ca(V)beta. Here, we studied the effect of
      mutating residues located opposite to the AID-Ca(V)beta contact surface in
      Ca(V)1.2. Substitution of AID-exposed residues by the corresponding amino acids
      present in other Ca(V)alpha(1) subunits (E462R, K465N, D469S, and Q473K) hinders
      Ca(V)beta's ability to increase ionic-current to charge-movement ratio (I/Q)
      without changing the apparent affinity for Ca(V)beta. At the single channel
      level, these Ca(V)1.2 mutants coexpressed with Ca(V)beta(2a) visit high open
      probability mode less frequently than wild-type channels. On the other hand,
      Ca(V)1.2 carrying either a mutation in the conserved tryptophan residue (W470S,
      which impairs Ca(V)beta binding), or a deletion of the whole AID sequence, does
      not exhibit Ca(V)beta-induced increase in I/Q. In addition, we observed a shift
      in the voltage dependence of activation by +12 mV in the AID-deleted channel in
      the absence of Ca(V)beta, suggesting a direct participation of these residues in
      the modulation of channel activation. Our results show that Ca(V)beta-dependent
      potentiation arises primarily from changes in the modal gating behavior. We
      envision that Ca(V)beta spatially reorients AID residues that influence the
      channel gate. These findings provide a new framework for understanding modulation
      of VDCC gating by Ca(V)beta.

PMID- 18725533
TI  - Eran Meshorer: getting a chromatin perspective. Interview by Caitlin Sedwick.

PMID- 18725534
TI  - Self-eating from an ER-associated cup.
AB  - Since the first morphological description of autophagosomes in the early 1960s,
      two critical questions have been a matter of intense investigation and debate:
      what is the origin of the autophagosomal membrane and how is it formed? A study
      by Axe et al. (E.L. Axe, S.A. Walker, M. Manifava, P. Chandra, H.L. Roderick, A.
      Habermann, G. Griffiths, and N.T. Ktistakis. 2008. J. Cell Biol. 182:685-701)
      provides evidence that cup-shaped protrusions from the endoplasmic reticulum,
      named omegasomes, serve as platforms for autophagosome biogenesis in mammalian
      cells.

PMID- 18725535
TI  - Phosphorylation of the Arp2/3 complex is necessary to nucleate actin filaments.
AB  - The actin-related protein 2/3 (Arp2/3) complex is the primary nucleator of new
      actin filaments in most crawling cells. Nucleation-promoting factors (NPFs) of
      the Wiskott-Aldrich syndrome protein (WASP)/Scar family are the currently
      recognized activators of the Arp2/3 complex. We now report that the Arp2/3
      complex must be phosphorylated on either threonine or tyrosine residues to be
      activated by NPFs. Phosphorylation of the Arp2/3 complex is not necessary to bind
      NPFs or the sides of actin filaments but is critical for binding the pointed end
      of actin filaments and nucleating actin filaments. Mass spectrometry revealed
      phosphorylated Thr237 and Thr238 in Arp2, which are evolutionarily conserved
      residues. In cells, phosphorylation of only the Arp2 subunit increases in
      response to growth factors, and alanine substitutions of Arp2 T237 and T238 or
      Y202 inhibits membrane protrusion. These findings reveal an additional level of
      regulation of actin filament assembly independent of WASP proteins, and show that
      phosphorylation of the Arp2/3 complex provides a logical "or gate" capable
      integrating diverse upstream signals.

PMID- 18725536
TI  - TGFbeta induces SIK to negatively regulate type I receptor kinase signaling.
AB  - Signal transduction by transforming growth factor beta (TGFbeta) coordinates
      physiological responses in diverse cell types. TGFbeta signals via type I and
      type II receptor serine/threonine kinases and intracellular Smad proteins that
      regulate transcription. Strength and duration of TGFbeta signaling is largely
      dependent on a negative-feedback program initiated during signal progression. We
      have identified an inducible gene target of TGFbeta/Smad signaling, the salt
      inducible kinase (SIK), which negatively regulates signaling together with Smad7.
      SIK and Smad7 form a complex and cooperate to down-regulate the activated type I
      receptor ALK5. We further show that both the kinase and ubiquitin-associated
      domain of SIK are required for proper ALK5 degradation, with ubiquitin
      functioning to enhance SIK-mediated receptor degradation. Loss of endogenous SIK
      results in enhanced gene responses of the fibrotic and cytostatic programs of
      TGFbeta. We thus identify in SIK a negative regulator that controls TGFbeta
      receptor turnover and physiological signaling.

PMID- 18725537
TI  - Heat shock and oxygen radicals stimulate ubiquitin-dependent degradation mainly
      of newly synthesized proteins.
AB  - Accumulation of misfolded oxidant-damaged proteins is characteristic of many
      diseases and aging. To understand how cells handle postsynthetically damaged
      proteins, we studied in Saccharomyces cerevisiae the effects on overall protein
      degradation of shifting from 30 to 38 degrees C, exposure to reactive oxygen
      species generators (paraquat or cadmium), or lack of superoxide dismutases.
      Degradation rates of long-lived proteins (i.e., most cell proteins) were not
      affected by these insults, even when there was widespread oxidative damage to
      proteins. However, exposure to 38 degrees C, paraquat, cadmium, or deletion of
      SOD1 enhanced two- to threefold the degradation of newly synthesized proteins. By
      1 h after synthesis, their degradation was not affected by these treatments.
      Degradation of these damaged cytosolic proteins requires the ubiquitin-proteasome
      pathway, including the E2s UBC4/UBC5, proteasomal subunit RPN10, and the CDC48
      UfD1-NPL4 complex. In yeast lacking these components, the nondegraded
      polypeptides accumulate as aggregates. Thus, many cytosolic proteins proceed
      through a prolonged "fragile period" during which they are sensitive to
      degradation induced by superoxide radicals or increased temperatures.

PMID- 18725538
TI  - Autophagosome formation from membrane compartments enriched in
      phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic
      reticulum.
AB  - Autophagy is the engulfment of cytosol and organelles by double-membrane vesicles
      termed autophagosomes. Autophagosome formation is known to require
      phosphatidylinositol 3-phosphate (PI(3)P) and occurs near the endoplasmic
      reticulum (ER), but the exact mechanisms are unknown. We show that double FYVE
      domain-containing protein 1, a PI(3)P-binding protein with unusual localization
      on ER and Golgi membranes, translocates in response to amino acid starvation to a
      punctate compartment partially colocalized with autophagosomal proteins.
      Translocation is dependent on Vps34 and beclin function. Other PI(3)P-binding
      probes targeted to the ER show the same starvation-induced translocation that is
      dependent on PI(3)P formation and recognition. Live imaging experiments show that
      this punctate compartment forms near Vps34-containing vesicles, is in dynamic
      equilibrium with the ER, and provides a membrane platform for accumulation of
      autophagosomal proteins, expansion of autophagosomal membranes, and emergence of
      fully formed autophagosomes. This PI(3)P-enriched compartment may be involved in
      autophagosome biogenesis. Its dynamic relationship with the ER is consistent with
      the idea that the ER may provide important components for autophagosome
      formation.

PMID- 18725539
TI  - In vivo reconstitution of autophagy in Saccharomyces cerevisiae.
AB  - Autophagy is a major intracellular degradative pathway that is involved in
      various human diseases. The role of autophagy, however, is complex; although the
      process is generally considered to be cytoprotective, it can also contribute to
      cellular dysfunction and disease progression. Much progress has been made in our
      understanding of autophagy, aided in large part by the identification of the
      autophagy-related (ATG) genes. Nonetheless, our understanding of the molecular
      mechanism remains limited. In this study, we generated a Saccharomyces cerevisiae
      multiple-knockout strain with 24 ATG genes deleted, and we used it to carry out
      an in vivo reconstitution of the autophagy pathway. We determined minimum
      requirements for different aspects of autophagy and studied the initial protein
      assembly steps at the phagophore assembly site. In vivo reconstitution enables
      the study of autophagy within the context of the complex regulatory networks that
      control this process, an analysis that is not possible with an in vitro system.

PMID- 18725540
TI  - SopB promotes phosphatidylinositol 3-phosphate formation on Salmonella vacuoles
      by recruiting Rab5 and Vps34.
AB  - Salmonella colonizes a vacuolar niche in host cells during infection. Maturation
      of the Salmonella-containing vacuole (SCV) involves the formation of
      phosphatidylinositol 3-phosphate (PI(3)P) on its outer leaflet. SopB, a bacterial
      virulence factor with phosphoinositide phosphatase activity, was proposed to
      generate PI(3)P by dephosphorylating PI(3,4)P2, PI(3,5)P2, and PI(3,4,5)P3. Here,
      we examine the mechanism of PI(3)P formation during Salmonella infection. SopB is
      required to form PI(3,4)P2/PI(3,4,5)P3 at invasion ruffles and PI(3)P on nascent
      SCVs. However, we uncouple these events experimentally and reveal that SopB does
      not dephosphorylate PI(3,4)P2/PI(3,4,5)P3 to produce PI(3)P. Instead, the
      phosphatase activity of SopB is required for Rab5 recruitment to the SCV. Vps34,
      a PI3-kinase that associates with active Rab5, is responsible for PI(3)P
      formation on SCVs. Therefore, SopB mediates PI(3)P production on the SCV
      indirectly through recruitment of Rab5 and its effector Vps34. These findings
      reveal a link between phosphoinositide phosphatase activity and the recruitment
      of Rab5 to phagosomes.

PMID- 18725541
TI  - uPAR promotes formation of the p130Cas-Crk complex to activate Rac through
      DOCK180.
AB  - The urokinase-type plasminogen activator receptor (uPAR) drives tumor cell
      membrane protrusion and motility through activation of Rac; however, the pathway
      leading from uPAR to Rac activation has not been described. In this study we
      identify DOCK180 as the guanine nucleotide exchange factor acting downstream of
      uPAR. We show that uPAR cooperates with integrin complexes containing beta(3)
      integrin to drive formation of the p130Cas-CrkII signaling complex and activation
      of Rac, resulting in a Rac-driven elongated-mesenchymal morphology, cell
      motility, and invasion. Our findings identify a signaling pathway underlying the
      morphological changes and increased cell motility associated with uPAR
      expression.

PMID- 18725542
TI  - Integrins control the positioning and proliferation of follicle stem cells in the
      Drosophila ovary.
AB  - Adult stem cells are maintained in specialized microenvironments called niches,
      which promote self-renewal and prevent differentiation. In this study, we show
      that follicle stem cells (FSCs) in the Drosophila melanogaster ovary rely on cues
      that are distinct from those of other ovarian stem cells to establish and
      maintain their unique niche. We demonstrate that integrins anchor FSCs to the
      basal lamina, enabling FSCs to maintain their characteristic morphology and
      position. Integrin-mediated FSC anchoring is also essential for proper
      development of differentiating prefollicle cells that arise from asymmetrical FSC
      divisions. Our results support a model in which FSCs contribute to the formation
      and maintenance of their own niche by producing the integrin ligand, laminin A
      (LanA). Together, LanA and integrins control FSC proliferation rates, a role that
      is separable from their function in FSC anchoring. Importantly, LanA-integrin
      function is not required to maintain other ovarian stem cell populations,
      demonstrating that distinct pathways regulate niche-stem cell communication
      within the same organ.

PMID- 18725544
TI  - Contribution of down-regulation of intestinal and hepatic cytochrome P450 3A to
      increased absorption of cyclosporine A in a rat nephrosis model.
AB  - This study examined the contribution of changes in regulation of intestinal and
      hepatic cytochrome P450 3A (CYP3A) and multidrug resistance transporter 1 (Mdr1)
      to absorption of cyclosporine A (CsA) in a rat nephrosis model. Interleukin (IL)
      6 was also measured. Puromycin aminonucleoside at a dose of 20 mg/100 g was
      administered intravenously. Tissue samples were dissected out from the upper and
      middle intestines and liver after development of nephrosis to measure the
      expression levels of mRNA and protein. CsA at a dose of 0.5 mg/100 g was
      administered into a closed loop of the upper and middle intestines. Blood from
      the inferior vena cava (IVC) and portal vein was taken until 30 min after
      administration. The expression levels of CYP3A decreased markedly, whereas those
      of Mdr1 showed large interindividual variations for all of the tissues in the
      nephrotic rats. Plasma concentrations of CsA reached higher levels in the
      nephrotic than in the control rats and were higher when administered from the
      upper than the middle intestine in both the portal vein and IVC. IL-6 increased
      in urine in the nephrotic rats. In summary, intestinal and hepatic CYP3A were
      down-regulated in the nephrosis model accompanying the increased levels of IL-6.
      Consistent results were not obtained for the regulation of Mdr1. In conclusion,
      these findings suggest that the down-regulation of CYP3A in the upper intestine
      and liver predominantly contributes to the increase in CsA absorption, and Mdr1
      showed less contribution in this rat nephrosis model.

PMID- 18725543
TI  - Inhibition of anandamide hydrolysis by cyclohexyl carbamic acid 3'-carbamoyl-3-yl
      ester (URB597) reverses abuse-related behavioral and neurochemical effects of
      nicotine in rats.
AB  - Emerging evidence suggests that the rewarding, abuse-related effects of nicotine
      are modulated by the endocannabinoid system of the brain. For example,
      pharmacological blockade or genetic deletion of cannabinoid CB(1) receptors can
      reduce or eliminate many abuse-related behavioral and neurochemical effects of
      nicotine. Furthermore, doses of Delta(9)-tetrahydrocannabinol and nicotine that
      are ineffective when given alone can induce conditioned place preference when
      given together. These previous studies have used systemically administered CB(1)
      receptor agonists and antagonists and gene deletion techniques, which affect
      cannabinoid CB(1) receptors throughout the brain. A more functionally selective
      way to alter endocannabinoid activity is to inhibit fatty acid amide hydrolase
      (FAAH), thereby magnifying and prolonging the effects of the endocannabinoid
      anandamide only when and where it is synthesized and released on demand. Here, we
      combined behavioral and neurochemical approaches to evaluate whether the FAAH
      inhibitor URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester) could alter
      the abuse-related effects of nicotine in rats. We found that URB597, at a dose
      (0.3 mg/kg) that had no behavioral effects by itself, prevented development of
      nicotine-induced conditioned place preference (CPP) and acquisition of nicotine
      self-administration. URB597 also reduced nicotine-induced reinstatement in both
      CPP and self-administration models of relapse. Furthermore, in vivo microdialysis
      showed that URB597 reduced nicotine-induced dopamine elevations in the nucleus
      accumbens shell, the terminal area of the brain's mesolimbic reward system. These
      findings suggest that FAAH inhibition can counteract the addictive properties of
      nicotine and that FAAH may serve as a new target for development of medications
      for treatment of tobacco dependence.

PMID- 18725545
TI  - Travel medicine and HIV infection.
AB  - The number of HIV-infected persons who travel is increasing. This increase arises
      from those who have benefited from advances in antiretroviral therapy. The key to
      successful travel is careful pre-trip planning although many patients do not
      obtain advice before travelling. Travel advice for HIV patients is becoming
      increasingly specialized, and includes travel vaccination and highly active
      antiretroviral therapy-related issues. A closer collaboration between HIV and
      travel health clinics could provide better care for HIV-infected individuals.

PMID- 18725546
TI  - How men with non-chlamydial, non-gonococcal urethritis are managed in
      Australasia.
AB  - The aim of this study was to ascertain how sexual health physicians in Australia
      and New Zealand manage men with chlamydia-negative non-gonococcal urethritis
      (NGU), particularly in relation to the notification of their female sexual
      partners. In July 2006, a cross-section survey was sent out to all the members of
      the Australasian Chapter of Sexual Health Medicine. Seventy-three percent of
      sexual health physicians believed that female partners of men who present with
      chlamydia-negative NGU were at risk of adverse reproductive health outcomes. At
      least 62% usually initiated some form of partner notification of female partners
      of men with chlamydia-negative NGU. However, only 19% (21/111) of sexual health
      physicians routinely tested for, and only 65% sometimes tested for, pathogens
      other than Neisseria gonorrhoeae and Chlamydia trachomatis in men presenting with
      NGU. These included Mycoplasma genitalium, herpes simplex virus, ureaplasma
      species, Trichomonas vaginalis and adenoviruses.

PMID- 18725547
TI  - Measuring the gap: from Home Office to the National Health Service in the
      provision of a one-stop shop sexual health service in a female prison in the UK.
AB  - The Genitourinary (GU) Medicine Service was transferred from the Home Office to
      the NHS from April 2006 at this female prison to give prisoners access to the
      same quality of health care as the general public. Medline search showed no
      published data on the prevalence of sexually transmitted infections (STIs) among
      female prisoners in the UK. The main aim was to develop a one stop sexual health
      shop and to determine the prevalence and risk factors for STIs, to determine the
      uptake rate for HIV testing, hepatitis B vaccination and cervical cytology along
      with requests for usage of contraceptive services. Challenges were met when
      introducing change to bring the services in line with the local GU medicine
      clinic. Review of the service at one year along with retrospective case note
      review from May 2006 to August 2007 was done. Of the 545 new patients seen,
      history of substance abuse, IVDU, sexual abuse, sex worker and past history of
      hepatitis C virus and chlamydia were 86%, 41%,12%, 6%, 17% and 24%
      respectively.The uptake rate for both STI screen and blood-borne viruses (BBVs)
      testing was high at 87% and 69.3% respectively. STI was diagnosed in 19.6%.
      Prevalence rates were: Trichomonas vaginalis (TV) 8.2%, chlamydia 5.3%,
      gonorrhoea 0.2%, genital warts 5.3%, HIV 0.8%, hepatitis C virus 12% and
      hepatitis B virus 11%. The uptake rate for 1(st) dose hepatitis B vaccination and
      cervical cytology were 70% and 92% respectively, 36 accessed contraceptive
      services. Provision of one stop shop in a female prison is feasible and
      practical. STIs, particularly TV, and BBVs prevalence is high among the female
      inmates. Prevention methods targeting this population needs to be intensified.

PMID- 18725548
TI  - Condom 'turn offs' among adults: an exploratory study.
AB  - An exploratory study compared the prevalence of multiple types of condom
      associated 'turn offs' in men and women. Nearly 2000 people completed a web-based
      questionnaire. Data were analysed from 464 men and women who reported that
      condoms had turned them off the last time they were used. Gender differences were
      not observed for the majority (9) of 15 turn offs. The most common turn offs
      related to loss of pleasure. For example, more than three-quarters of the men and
      nearly 40% of the women reported decreased sexual sensation (P = 0.0001). Putting
      on condoms was reported by 43.2% of the men versus 30.2% of the women (P = 0.02).
      Smell was a relatively frequent turn off, with about one-third indicating this
      issue and no significant gender difference (P = 0.32). Turn offs pertaining to
      arousal and orgasm were also common. Findings suggest that numerous physical and
      psychological condom turn offs may be experienced by men and women while using
      male condoms. Although some turn offs differed as a function of gender, there was
      remarkable similarity between men and women.

PMID- 18725549
TI  - Genotypic distribution of hepatitis C among hepatitis C and HIV co-infected
      patients in Brazil.
AB  - Information on hepatitis C virus (HCV) genotypic distribution among HIV-HCV co
      infected patients is lacking in Brazil as well as other Latin American countries.
      The objective of this study was to evaluate the level of exposure to different
      risk factors associated with HCV transmission among a group of co-infected
      patients and to characterize the genotypic distribution of HCV in this cluster. A
      series of 100 HIV-HCV co-infected patients was analysed. The data to be analysed
      were collected from specific laboratory tests. Information was collected through
      a questionnaire. HCV genotyping was carried out by sequencing the 5' non-coding
      region of HCV. Chi-square and Fischer association tests or Kruskal-Wallis test
      were used to study the association between HCV transmission-related variables and
      the established genotypes. In conclusion, exposure to multiple risk factors
      associated with HCV transmission was common among HIV co-infected patients and an
      association between HCV genotype 3 and intravenous drug user was observed.

PMID- 18725550
TI  - Independent clinical predictors of impaired response to hepatitis B vaccination
      in HIV-infected persons.
AB  - Protective response rates to hepatitis B (HB) vaccination have been reported as
      low as 18-62% in HIV-infected persons. The relative importance of various
      predictors for this poor response has not been fully characterized. In this
      retrospective cohort study, we examined the relationship between clinical
      characteristics and vaccine non-response (HB surface antibody <10 IU/L) among
      patients attending an urban HIV clinic. Among the 97 patients who met the
      inclusion criteria, 43 (44%) developed a protective antibody response. In
      multivariate analyses, age >40 years (odds ratio [OR] 3.03 [95% confidence
      interval [CI], 1.14-8.06]; P = 0.026) and alcohol abuse (OR 4.92 [95% CI, 1.72
      20.89]; P = 0.007) were independent predictors of failure to develop vaccine
      response. In addition, CD4 nadir <200 (OR 7.24 [95% CI, 1.91-27.41]; P = 0.004),
      rather than CD4 current to vaccination, remained a strong independent risk
      factor. Patients with HIV viral suppression on highly active antiretroviral
      therapy had a significantly lower rate of vaccine failure (OR 0.31 [95% CI, 0.11
      0.91]; P = 0.033), after adjusting for these other covariates. Our findings
      underscore the importance of confirming seroconversion after HB vaccination in
      HIV-infected patients and initiating vaccination early in the course of HIV
      infection.

PMID- 18725551
TI  - Prevalence and predictors of high-risk human papillomavirus infection in a
      population-based sample of women in rural Uganda.
AB  - High-risk genital human papillomavirus (HPV) infection is aetiologically linked
      to cervical cancer; however, data on the prevalence and determinants of high-risk
      HPV infection in Uganda are limited. We conducted a population-based cross
      sectional survey among 18-49-year-old women in rural Southwest Uganda. The
      primary outcome was presence or absence of high-risk HPV DNA (for genotypes 16,
      18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68) in the genital secretions as
      determined by HPV DNA Hybrid Capture 2 assay (Digene Corp, Beltsville, MD, USA).
      In 314 women who participated, the prevalence of high-risk HPV was 17.2% (54/314;
      95% confidence interval [CI]: 13-21). Older women had a lower proportion of high
      risk HPV infection; with a 9% decrease in the odds ratio (OR) of high-risk HPV
      infection per year increase in age (OR = 0.91; 95% CI: 0.86, 0.96). The odds of
      detecting high-risk HPV infection was higher among women who were previously
      tested positive for HIV (OR = 12.1; 95% CI: 2.8, 52.3). In this population of
      rural Ugandan women, the prevalence of high-risk cervical HPV infection was high.
      Information on predictors of high-risk HPV infection and intention to receive a
      vaccine can guide future immunization initiatives for young sexually active
      women.

PMID- 18725552
TI  - Human papillomavirus detection and typification in cutaneous and mucosal lesions
      of HIV-seropositive patients.
AB  - High-risk human papillomavirus (HPV) in a lesion is related to an increased
      chance of neoplasic transformation, especially when with immunosuppression, as in
      HIV infection. We investigated HPV frequency in cutaneous and mucosal lesions of
      HIV-seropositive male patients. The frequency of malignancy, its association with
      the HPV type detected and some clinical variables were also assessed. A total of
      38 lesions from 27 patients were studied in a period of 18 months. The biopsied
      fragment was submitted to HPV detection and typification, through polymerase
      chain reaction with generic (MY09/11) and specific (types 6, 11, 16 and 18)
      primers. HPV frequency was 63.2%, with detection of HPV types 6, 11 or 16 in 18
      lesions and with multi-infection in three. There was low detection of high-risk
      HPV (type 16, 18.4%) and no HPV type 18. Of the lesions, 36.8% were already
      premalignant or malignant, and the frequency of moderate or severe dysplasia was
      higher in the study patients than that described in the HIV-seronegative
      population. High-risk HPV (type 16) was detected in four benign lesions and low
      risk HPV (type 6) in three premalignant genital lesions. There was no significant
      association between the clinical variables and an increase in the prevalence of
      premalignant or malignant lesions.

PMID- 18725553
TI  - Black and minority ethnic men who have sex with men: a London genitourinary
      medicine clinic experience.
AB  - The aim was to examine sexual behaviour and rates of sexually transmitted
      infections (STIs) in black and minority ethnic (BME) men who have sex with men
      (MSM) attending a London genitourinary medicine clinic. A case-note review of BME
      MSM (n = 203) attending our service between 1 April 2005 and 31 March 2006 was
      carried out. BME MSM were those who self-identified as being of Black (Caribbean,
      African or Other), South Asian (Indian, Pakistani, Bangladeshi or Sri Lankan) and
      Chinese/South-East Asian (Malaysian, Thai, Filipino, Japanese) ethnicities.
      Consecutively attending self-identified white British (WB) MSM (n = 203) were
      used as a comparative group. BME MSM were significantly more likely to report
      unprotected anal intercourse with casual male partners in the preceding three
      months (P = 0.0016) and were more likely to report female sexual partners (P =
      0.0018). Rectal gonorrhoea was more common in WB MSM (P = 0.02). Numbers of other
      bacterial STIs and HIV infection were similar in both groups. The higher reported
      rates of risk behaviour in BME MSM are of concern and support the need for
      focussed sexual health promotion.

PMID- 18725554
TI  - Qualitative and quantitative aspects of the serological diagnosis of early
      syphilis.
AB  - The aim of the present study was to evaluate the use of various serological tests
      in the diagnosis of early syphilis. The Murex enzyme immunoassay (EIA) test was
      used for screening; the Venereal Diseases Research Laboratory (VDRL) test, the
      Treponema pallidum particle agglutination assay (TPPA) and the Mercia
      antitreponemal IgM EIA were used in all the patients with a positive screening
      test and in those with suspected syphilis or in known contacts. In 89 cases of
      primary syphilis, the Murex EIA screening test was positive in 67 (75%) patients,
      the Mercia IgM EIA in 80 (90%) cases, the VDRL in 60 (67%) cases and the TPPA in
      85 (96%) cases. All the tests were positive in 68 patients with secondary
      syphilis. In 72 cases of early latent syphilis, the Murex EIA screening test was
      positive in 68 (94%) patients, the Mercia IgM EIA in 50 (69%) cases, the VDRL in
      61 (85%) cases and the TPPA in 68 (94%) cases. The Mercia IgM EIA was the only
      test positive in four (6%) of these cases; these four patients were known
      contacts. Antibody titres in the VDRL and TPPA increased as the infection
      progressed.

PMID- 18725556
TI  - Expanding HIV rapid testing via point-of-care paraprofessionals.
AB  - HIV counselling and testing has traditionally been performed by highly trained
      professionals in clinical settings. With HIV rapid testing, a reliable and easy
      to use diagnostic tool, paraprofessionals can be trained to administer on-site
      HIV testing in a variety of non-traditional settings, broadening the HIV
      detection rates. Our objective was to create a robust and sustainable
      paraprofessional training module to facilitate off-site HIV rapid testing in non
      clinical settings. Trainees attended a series of training sessions involving HIV
      education, rapid test instructions and communication techniques. After these
      sessions, trainees competently carried out HIV rapid testing in homeless shelters
      throughout the Los Angeles county. Agencies motivated to expand HIV screening
      programmes may use trained paraprofessionals to administer a full range of
      services (recruitment, pretest counselling, test administration, interpretation
      of results, post-test counselling and documentation) through this training model
      and enabling more highly trained healthcare providers to focus efforts on
      patients identified as HIV-positive.

PMID- 18725555
TI  - Management of under-16-year olds in UK genitourinary medicine clinics: British Co
      operative Clinical Group.
AB  - In 2004, the management of under-16-year olds in UK genitourinary (GU) medicine
      clinics was surveyed. Questionnaires were sent to 185 lead GU medicine
      consultants. A total of 111 questionnaires were returned (60%). Ninety-eight
      percent of respondents managed young people aged 13-16. Fifty percent managed
      under 13-year-olds. Twenty-nine percent of respondents ran dedicated young
      people's clinics. Ninety-eight percent were aware of the National Guidelines, and
      74% had adopted them. Fifty-seven percent had a named departmental child
      protection lead. Thirty-seven percent of consultants had received training
      specific to child protection issues in GU medicine. Improvements had been made
      since a similar survey published in 2001, but the need for further training was
      still apparent.

PMID- 18725557
TI  - Attending an STI Foundation course increases chlamydia testing in primary care,
      but not HIV testing.
AB  - The Sexually Transmitted Infection Foundation course (STIF) is a recommended
      training course for UK general practitioners (GPs) and others delivering sexual
      health services in the community. We assessed the impact of attending the course
      on testing for HIV and chlamydia. Thirty-one GPs attending Brighton STIF courses
      were identified and the laboratory database was searched to identify all
      chlamydia and HIV tests they requested in the three months prior to attending,
      the first three months after attending and the subsequent three months. Three
      hundred and eight chlamydia tests were performed precourse, 390 postcourse and
      342 in the following three months. This represented a significant increase from
      baseline to postcourse (P = 0.007), which was lost by three to six months (P =
      0.25). The proportion of positives did not change. A total of 98, 111 and 131 HIV
      tests were performed in the three time periods of which; none were positive.
      Barriers other than training may need to be overcome to increase HIV testing in
      primary care.

PMID- 18725559
TI  - Unilateral penile swelling: an unusual presentation of primary syphilis?
AB  - Primary syphilis is characterized by a solitary, painless, indurated ulcer
      (chancre) at the site of inoculation, with associated inguinal lymph nodes that
      are enlarged, rubbery, painless and discrete. We report a case of syphilis that
      presented with penile swelling associated with tender lymphadenopathy and review
      the literature concerning this unusual presentation of early syphilis.

PMID- 18725558
TI  - Prevalence and predictors of herpes simplex virus type 2 infection among female
      sex workers in Yunnan Province, China.
AB  - The objective of this study was to determine the seroprevalence of herpes simplex
      virus type 2 (HSV-2), and to evaluate the relationship between HSV-2 infection
      and sociodemographic factors and the sexual practices of female sex workers
      (FSWs) in Kaiyuan city, Yunnan Province, China. This cross-sectional study
      involved 737 FSWs and was carried out from March to May 2006 with confidential
      interviews and laboratory tests for HSV-2 and other sexually transmitted
      infections (STI). HSV-2 was the most common STI (68%), followed by Chlamydia
      trachomatis (26%), Trichomonas vaginalis (11%), Neisseria gonorrhoeae (8%) and
      syphilis (7%). Prevalence of HIV-1 was 10.3%. Adjusted odds ratios of HSV-2
      seroprevalence were 2.6 (95% CI [confidence interval]: 1.30-5.38) for HIV-1
      infection, 2.0 (95% CI: 1.33-3.16) for vaginal douching, 2.0 (95% CI: 0.45-0.86)
      for condom breaking or falling off during sexual intercourse with the client in
      the previous week, 1.8 (95% CI: 1.07-3.18) for > or =5 years of commercial sex
      work, 1.6 (95% CI: 1.08-2.33) for > or =5 clients in the previous week, 0.6 (95%
      CI: 0.45-0.86) for > or =9 years of education. This study identifies a very high
      prevalence of HSV-2 infections among FSWs in Yunnan Province, with only a few who
      reported a prior history of genital herpes. HSV-2 serological screening and
      suppressive therapy should be considered for study populations. Education on the
      importance of diagnosis, treatment and prevention may help control the spread of
      HSV-2 infection.

PMID- 18725560
TI  - Fatal outcome of nevirapine-associated toxic epidermal necrolysis.
AB  - The irregular use of antiretroviral therapy (ART) can result in ART-resistance
      but can also lead to a sensitization between agents with a cross-sensitivity. We
      report a case of nevirapine-associated toxic epidermal necrolysis resulting in
      death in an HIV-infected man.

PMID- 18725561
TI  - Successful prevention of multidrug resistant HIV mother-to-child transmission
      with enfuvirtide use in late pregnancy.
AB  - The availability of antiretroviral therapy has dramatically reduced the risk of
      HIV mother-to-child transmission (MTCT). However, mothers infected with multidrug
      resistant HIV (MDR-HIV) are at increased risk of MTCT. We report the case of a
      pregnant patient infected with MDR-HIV in whom MTCT was avoided with enfuvirtide
      use in late pregnancy and elective caesarean section.

PMID- 18725562
TI  - Patient-delivered partner medication.

PMID- 18725563
TI  - Reassessment of BV causation.

PMID- 18725564
TI  - Achieving 48-hour access targets in genitourinary medicine.

PMID- 18725565
TI  - Penicillin treatment for early syphilis in the presence of HIV-1 infection: the
      long or the short of it?

PMID- 18725566
TI  - VEGF-D: a modifier of embryonic lymphangiogenesis.

PMID- 18725567
TI  - Shear tango: dance of the ADAMTS13/VWF complex.

PMID- 18725568
TI  - Where does von Willebrand factor go?

PMID- 18725569
TI  - Genomic complexity in chronic lymphocytic leukemia.

PMID- 18725570
TI  - Complement dances with T cells.

PMID- 18725571
TI  - Diamond-Blackfan anemia: a new facet.

PMID- 18725572
TI  - GASing up iron delivery via STAT5.

PMID- 18725573
TI  - Blood group antigens reveal their maker.

PMID- 18725576
TI  - Valganciclovir versus valaciclovir for prevention of alemtuzumab-induced
      cytomegalovirus reactivation: what are the implications for routine clinical
      practice?

PMID- 18725574
TI  - CD4 T cells: fates, functions, and faults.
AB  - In 1986, Mosmann and Coffman identified 2 subsets of activated CD4 T cells, Th1
      and Th2 cells, which differed from each other in their pattern of cytokine
      production and their functions. Our understanding of the importance of the
      distinct differentiated forms of CD4 T cells and of the mechanisms through which
      they achieve their differentiated state has greatly expanded over the past 2
      decades. Today at least 4 distinct CD4 T-cell subsets have been shown to exist,
      Th1, Th2, Th17, and iTreg cells. Here we summarize much of what is known about
      the 4 subsets, including the history of their discovery, their unique cytokine
      products and related functions, their distinctive expression of cell surface
      receptors and their characteristic transcription factors, the regulation of their
      fate determination, and the consequences of their abnormal activation.

PMID- 18725577
TI  - SNP309 as predictor for sensitivity of CLL cells to the MDM2 inhibitor nutlin-3a.

PMID- 18725575
TI  - B lymphocytes: how they develop and function.
AB  - The discovery that lymphocyte subpopulations participate in distinct components
      of the immune response focused attention onto the origins and function of
      lymphocytes more than 40 years ago. Studies in the 1960s and 1970s demonstrated
      that B and T lymphocytes were responsible primarily for the basic functions of
      antibody production and cell-mediated immune responses, respectively. The decades
      that followed have witnessed a continuum of unfolding complexities in B-cell
      development, subsets, and function that could not have been predicted. Some of
      the landmark discoveries that led to our current understanding of B lymphocytes
      as the source of protective innate and adaptive antibodies are highlighted in
      this essay. The phenotypic and functional diversity of B lymphocytes, their
      regulatory roles independent of antibody production, and the molecular events
      that make this lineage unique are also considered. Finally, perturbations in B
      cell development that give rise to certain types of congenital immunodeficiency,
      leukemia/lymphoma, and autoimmune disease are discussed in the context of normal
      B-cell development and selection. Despite the significant advances that have been
      made at the cellular and molecular levels, there is much more to learn, and cross
      disciplinary studies in hematology and immunology will continue to pave the way
      for new discoveries.

PMID- 18725579
TI  - Blood pressure in children with chronic kidney disease: a report from the Chronic
      Kidney Disease in Children study.
AB  - To characterize the distribution of blood pressure (BP), prevalence, and risk
      factors for hypertension in pediatric chronic kidney disease, we conducted a
      cross-sectional analysis of baseline BPs in 432 children (mean age 11 years; 60%
      male; mean glomerular filtration rate 44 mL/min per 1.73 m(2)) enrolled in the
      Chronic Kidney Disease in Children cohort study. BPs were obtained using an
      aneroid sphygmomanometer. Glomerular filtration rate was measured by iohexol
      disappearance. Elevated BP was defined as BP >or=90th percentile for age, gender,
      and height. Hypertension was defined as BP >or=95th percentile or as self
      reported hypertension plus current treatment with antihypertensive medications.
      For systolic BP, 14% were hypertensive and 11% were prehypertensive (BP 90th to
      95th percentile); 68% of subjects with elevated systolic BP were taking
      antihypertensive medications. For diastolic BP, 14% were hypertensive and 9% were
      prehypertensive; 53% of subjects with elevated diastolic BP were taking
      antihypertensive medications. Fifty-four percent of subjects had either systolic
      or diastolic BP >or=95th percentile or a history of hypertension plus current
      antihypertensive use. Characteristics associated with elevated BP included black
      race, shorter duration of chronic kidney disease, absence of antihypertensive
      medication use, and elevated serum potassium. Among subjects receiving
      antihypertensive treatment, uncontrolled BP was associated with male sex, shorter
      chronic kidney disease duration, and absence of angiotensin-converting enzyme
      inhibitor or angiotensin receptor blocker use. Thirty-seven percent of children
      with chronic kidney disease had either elevated systolic or diastolic BP, and 39%
      of these were not receiving antihypertensives, indicating that hypertension in
      pediatric chronic kidney disease may be frequently under- or even untreated.
      Treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor
      blockers may improve BP control in these patients.

PMID- 18725580
TI  - Impact of high-normal blood pressure on the risk of cardiovascular disease in a
      Japanese urban cohort: the Suita study.
AB  - Few prospective studies have examined the association between high-normal blood
      pressure and cardiovascular disease (CVD) in Asia. We examined the impact of high
      normal blood pressure on the incidence of CVD in a general urban population
      cohort in Japan. We studied 5494 Japanese individuals (ages 30 to 79 years
      without CVD at baseline) after completing a baseline survey who received follow
      up through December 2005. Blood pressure categories were defined on the basis of
      the ESH-ESC 2007 criteria. In 64 391 person-years of follow-up, we documented the
      incidence of 346 CVD events. The frequencies of high-normal blood pressure and
      hypertension Stage 1 and Stage >or=2 were 18.0%, 20.1%, and 10.1% for men and
      15.9%, 15.6%, and 8.8% for women, respectively. Antihypertensive drug users were
      also classified into the baseline blood pressure categories. Compared with the
      optimal blood pressure group, the multivariable hazard ratios (95% confidence
      intervals) of CVD for normal and high-normal blood pressure and hypertension
      Stage 1 and Stage >or=2 were 2.04 (1.19 to 3.48), 2.46 (1.46 to 4.14), 2.62 (1.59
      to 4.32), and 3.95 (2.37 to 6.58) in men and 1.12 (0.59 to 2.13), 1.54 (0.85 to
      2.78), 1.35 (0.75 to 2.43), and 2.86 (1.60 to 5.12) in women, respectively. The
      risks of myocardial infarction and stroke for each blood pressure category were
      similar to those of CVD. Population-attributable fractions of high-normal blood
      pressure and hypertension for CVD were 12.2% and 35.3% in men and 7.1% and 23.4%
      in women, respectively. In conclusion, high-normal blood pressure is a risk
      factor for the incidence of stroke and myocardial infarction in a general urban
      population of Japanese men.

PMID- 18725581
TI  - Effect of olmesartan on tissue expression balance between angiotensin II receptor
      and its inhibitory binding molecule.
AB  - We previously cloned a novel molecule interacting with angiotensin II (Ang II)
      type 1 receptor protein (ATRAP) and showed it to be an endogenous inhibitor of
      Ang II type 1 receptor signaling in cardiovascular cells. In this study, we
      tested a hypothesis that the balance of tissue expression of ATRAP and Ang II
      type 1 receptor is regulated in a tissue-specific manner during the development
      of hypertension and related cardiac hypertrophy. Concomitant with blood pressure
      increase and cardiac hypertrophy in spontaneously hypertensive rats, there was a
      constitutive decrease in the ratio of cardiac expression of ATRAP to Ang II type
      1 receptor. However, treatment with olmesartan, an Ang II type 1 receptor
      specific antagonist, either at a depressor or subdepressor dose, recovered the
      suppressed cardiac ATRAP to Ang II type 1 receptor ratio, which was accompanied
      by a decrease in Ang II type 1 receptor density, an inhibition of p38 mitogen
      activated protein kinase activity, and a regression of cardiac hypertrophy.
      Furthermore, Ang II stimulation suppressed the ATRAP to Ang II type 1 receptor
      ratio with hypertrophic responses in both the cardiomyocytes and rat hearts.
      These findings show a tissue-specific regulatory balancing of the expression of
      ATRAP and Ang II type 1 receptor during the development of hypertension and
      cardiac remodeling and further suggest that the upregulation of the tissue ATRAP
      to Ang II type 1 receptor ratio may be one of the therapeutic benefits of
      olmesartan beyond its blood pressure-lowering effect.

PMID- 18725582
TI  - Hypertension in children with chronic kidney disease: a call to action.

PMID- 18725583
TI  - No midpregnancy fall in diastolic blood pressure in women with a low educational
      level: the Generation R Study.
AB  - Low socioeconomic status has been associated with preeclampsia. The underlying
      mechanism, however, is unknown. Preeclampsia is associated with relatively high
      blood pressure levels in early pregnancy and with an absent midpregnancy fall in
      blood pressure. At present, little is known about the associations among
      socioeconomic status, blood pressure level in early pregnancy, blood pressure
      change during pregnancy, and preeclampsia. We studied these associations in 3142
      pregnant women participating in a population-based cohort study. Maternal
      educational level (high, midhigh, midlow, and low) was used as an indicator of
      socioeconomic status. Systolic and diastolic blood pressure was measured in
      early, mid-, and late pregnancy. Relative to women with high education, those
      with low and midlow education had higher mean systolic and diastolic blood
      pressure levels in early pregnancy; this was explained largely by a higher
      prepregnancy body mass index. Although women with high, midhigh, and midlow
      education had a significant midpregnancy fall in diastolic blood pressure, those
      with low education did not (change from early to midpregnancy: -0.38 mm Hg; 95%
      CI: -1.33 to 0.58). The latter could not be explained by prepregnancy body mass
      index, smoking, or alcohol consumption during pregnancy. The absence of a
      midpregnancy fall also tended to be related to the development of preeclampsia,
      especially among women with a low educational level (OR: 3.8; 95% CI: 0.80 to
      18.19). The absence of a midpregnancy fall in diastolic blood pressure in women
      with a low education level may be a sign of endothelial dysfunction that is
      manifested during pregnancy. This might partly explain these women's
      susceptibility to preeclampsia.

PMID- 18725584
TI  - Restorative effect of atrial natriuretic peptide or chronic neutral endopeptidase
      inhibition on blunted cardiopulmonary vagal reflexes in aged rats.
AB  - Arterial baroreflex function diminishes with age, but whether cardiopulmonary
      vagal reflexes are similarly altered with physiological aging has not been fully
      elucidated. In this study, predominantly cardiac high pressure mechanoreceptor
      activated (ramp baroreflex) and cardiopulmonary chemoreceptor-activated (von
      Bezold-Jarisch reflex) vagal reflexes in conscious, instrumented rats were
      impaired by 30% to 40% (P<0.05) in 24-month-old (n=12) compared with 6-month-old
      rats (n=12). To determine whether this is a restorable deficit, the influence of
      atrial natriuretic peptide (ANP), either by infusion or blockade of its
      breakdown, was studied. ANP infusion was previously shown to enhance Bezold
      Jarisch reflex and ramp baroreflex bradycardia in young adult rats. The present
      study confirmed that vagal reflex augmentation by ANP (50 pmol/kg per minute)
      also occurs in old rats (increased by 60+/-18% (Bezold-Jarisch reflex) and 91+/
      15% (ramp baroreflex; P<0.05). Direct vagal stimulation in anesthetized animals
      showed that the target for ANP was not the cardiac vagus itself in old rats
      (n=7), although in young rats only, we confirmed the published finding that ANP
      enhances vagal bradycardia (by 58+/-14%, n=7). Neutral endopeptidase 24.11
      degrades ANP and several other peptides. The neutral endopeptidase inhibitor
      candoxatrilat (5 mg/kg per day IV for 7 to 9 days) restored vagal reflex
      bradycardia in old rats (n=6) to levels similar to those in young neutral
      endopeptidase inhibitor-treated rats (n=6). Impaired cardiopulmonary vagal reflex
      control of heart rate is thus a feature of normal aging, and this deficit may be
      ameliorated by either ANP infusion or chronic neutral endopeptidase inhibition.

PMID- 18725585
TI  - Teaching NeuroImage: spinal extradural arachnoid cyst: a rare cause of back pain.

PMID- 18725586
TI  - Patient page. The placebo effect.

PMID- 18725588
TI  - Copper deficiency myeloneuropathy: a clue to clioquinol-induced subacute myelo
      optic neuropathy?

PMID- 18725589
TI  - Cognitive assessment and quantitative magnetic resonance metrics can help to
      identify benign multiple sclerosis.
AB  - BACKGROUND: The definition of benign multiple sclerosis (B-MS) is still
      controversial. This mainly takes into account the subject's motor ability, with
      little or no relevance to other important features such as cognition. Moreover,
      no paraclinical markers are currently available to reliably identify patients who
      will remain benign in the long term. OBJECTIVES: To assess, by using quantitative
      magnetic resonance (MR) metrics, differences in tissue damage between B-MS
      patients after dividing them into two groups on the basis of their cognitive
      performance. METHODS: Forty-seven B-MS patients (Expanded Disability Status Scale
      score </=3.0 and disease duration >/=15 years) underwent neuropsychological
      assessment through the Rao Brief Repeatable Battery and the Stroop Test. At that
      time, B-MS patients underwent conventional brain MR and magnetization transfer
      (MT) imaging. White matter lesion load, global and regional brain volumes, and MT
      ratio (MTr) in lesions and normal-appearing brain were measured. Quantitative MR
      measures were compared in cognitively impaired (CI-MS) and cognitively preserved
      (CP-MS) patients and in 24 demographically matched healthy controls. Test
      performance was correlated with MR changes in specific cortical regions. RESULTS:
      Eleven patients were classified as CI-MS, and 36 were classified as CP-MS. Both
      T2-weighted and T1-weighted lesion loads were higher (p = 0.05 and 0.001) in CI
      MS than in CP-MS patients. Furthermore, CI-MS patients were characterized by more
      pronounced decrease in neocortical volume (p = 0.005) and cortical MTr (p = 0.02)
      values than CP-MS patients. Finally, test performance correlated significantly
      with MR changes in relevant cortical regions. CONCLUSIONS: Cognitive assessment
      and quantitative magnetic resonance can help to reliably identify benign multiple
      sclerosis patients.

PMID- 18725590
TI  - Natural history of SMA IIIb: muscle strength decreases in a predictable sequence
      and magnitude.
AB  - OBJECTIVE: To assess the natural progression of muscle weakness in spinal
      muscular atrophy (SMA) IIIb. METHODS: Ten patients with SMA IIIb were followed
      for at least 10 years. Age at disease onset varied between 9 and 18 years.
      Patients were initially seen 2 to 10 years after disease onset. They were
      evaluated at approximately 2, 5, 10, 15, and 20 years of disease duration
      depending on the timing of their initial visit after onset. Medical Research
      Council (MRC) scale was used with particular attention to proximal muscles.
      RESULTS: The MRC grade declined with years in all of the muscles. The decline was
      usually not more than by one MRC grade for each 5-year period. There were 5-10
      year periods when some muscles appeared to remain stationary. The succession of
      weakness was first triceps, then biceps and deltoid for upper extremity muscles
      and first thigh adductors, then iliopsoas, then quadriceps femoris, then
      hamstrings, thigh abductors, and gluteus maximus for lower extremity muscles.
      There was a remarkable uniformity between patients in the MRC grade for each
      muscle at each stage: in the first 5 years of the disease, triceps, iliopsoas,
      thigh adductors, and quadriceps femoris were the muscles which had noticeable
      weakness. CONCLUSIONS: These findings show that strength in spinal muscular
      atrophy IIIb decreases over time, explaining the progressive functional loss. The
      sequence of weakness in the lower extremities suggests that the disease starts
      segmentally involving the upper lumbar segments of the medulla spinalis
      initially. The slowness of the deterioration may have implications for clinical
      trials.

PMID- 18725591
TI  - Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial
      neurosurgery.
AB  - BACKGROUND: Antiepileptic drugs are routinely given after craniotomy. Though
      phenytoin (PHT) is still the most commonly used agent, levetiracetam (LEV) is
      increasingly administered for this purpose. This retrospective study compared the
      use of LEV and PHT as monotherapy prophylaxis following supratentorial
      neurosurgery. METHODS: Patients receiving LEV monotherapy after supratentorial
      craniotomy were reviewed and compared to a control group of patients receiving
      PHT monotherapy. RESULTS: One of 105 patients taking LEV and 9/210 patients
      taking PHT had seizures within 7 days of surgery (p = 0.17). Adverse drug
      reactions requiring change in therapy during hospitalization occurred in 1/105
      patients taking LEV and 38/210 patients taking PHT (p < 0.001). Among patients
      followed for at least 12 months, 11/42 (26%) treated with LEV vs 42/117 (36%)
      treated with PHT developed epilepsy (p = 0.34); 64% remained on LEV, while 26%
      remained on PHT (p = 0.03). CONCLUSIONS: Both levetiracetam (LEV) and phenytoin
      (PHT) were associated with a low risk of early postoperative seizures and a
      moderate risk of later epilepsy. LEV was associated with significantly fewer
      early adverse reactions than PHT and with a higher retention rate in patients who
      were followed for at least 1 year and developed epilepsy.

PMID- 18725592
TI  - Second consensus statement on the diagnosis of multiple system atrophy.
AB  - BACKGROUND: A consensus conference on multiple system atrophy (MSA) in 1998
      established criteria for diagnosis that have been accepted widely. Since then,
      clinical, laboratory, neuropathologic, and imaging studies have advanced the
      field, requiring a fresh evaluation of diagnostic criteria. We held a second
      consensus conference in 2007 and present the results here. METHODS: Experts in
      the clinical, neuropathologic, and imaging aspects of MSA were invited to
      participate in a 2-day consensus conference. Participants were divided into five
      groups, consisting of specialists in the parkinsonian, cerebellar, autonomic,
      neuropathologic, and imaging aspects of the disorder. Each group independently
      wrote diagnostic criteria for its area of expertise in advance of the meeting.
      These criteria were discussed and reconciled during the meeting using consensus
      methodology. RESULTS: The new criteria retain the diagnostic categories of MSA
      with predominant parkinsonism and MSA with predominant cerebellar ataxia to
      designate the predominant motor features and also retain the designations of
      definite, probable, and possible MSA. Definite MSA requires neuropathologic
      demonstration of CNS alpha-synuclein-positive glial cytoplasmic inclusions with
      neurodegenerative changes in striatonigral or olivopontocerebellar structures.
      Probable MSA requires a sporadic, progressive adult-onset disorder including
      rigorously defined autonomic failure and poorly levodopa-responsive parkinsonism
      or cerebellar ataxia. Possible MSA requires a sporadic, progressive adult-onset
      disease including parkinsonism or cerebellar ataxia and at least one feature
      suggesting autonomic dysfunction plus one other feature that may be a clinical or
      a neuroimaging abnormality. CONCLUSIONS: These new criteria have simplified the
      previous criteria, have incorporated current knowledge, and are expected to
      enhance future assessments of the disease.

PMID- 18725593
TI  - The placebo treatments in neurosciences: New insights from clinical and
      neuroimaging studies.
AB  - Placebo (PL) treatment is a method utilized as a control condition in clinical
      trials. A positive placebo response is seen in up to 50% of patients with
      Parkinson disease (PD), pain syndromes, and depression. The response is more
      pronounced with invasive procedures or advanced disease. Physiologic and
      biochemical changes have been studied in an effort to understand the mechanisms
      underlying placebo-related clinical improvement. In PD, objective clinical
      improvements in parkinsonism correlate with dopaminergic activation of the
      striatum, documented by PET and with changes in cell firings of the subthalamic
      nucleus documented by single cell recordings. Dopaminergic pathways mediating
      reward may underlie PL-mediated improvement in PD. In pain syndromes, endogenous
      opioid release triggered by cortical activation, especially the rostral anterior
      cingulated cortex, is associated with PL-related analgesia and can be reversed by
      opioid antagonists. Covert treatment of an analgesic is less effective than overt
      treatment, suggesting an expectation component to clinical response. In
      depression, PL partially imitates selective serotonin reuptake inhibitor-mediated
      brain activation. Diseases lacking major "top-down" or cortically based
      regulation may be less prone to PL-related improvement.

PMID- 18725594
TI  - Levetiracetam as a possible cause of fulminant liver failure.

PMID- 18725595
TI  - Carrier erythrocyte entrapped thymidine phosphorylase therapy for MNGIE.

PMID- 18725597
TI  - Reflections: neurology and the humanities. The case of the collapsing man.

PMID- 18725598
TI  - Hearing and seeing: Unusual early signs of Wernicke encephalopathy.

PMID- 18725599
TI  - Kick and rush: paradoxical kinesia in Parkinson disease.

PMID- 18725600
TI  - Rating the approachability of faces in ALS.

PMID- 18725601
TI  - An alternative method for estimating efficacy of the AN1792 vaccine for Alzheimer
      disease.

PMID- 18725603
TI  - Microresearch: borrowing from the microfinance experience.

PMID- 18725604
TI  - Stopping anticoagulant therapy after an unprovoked venous thromboembolism.

PMID- 18725605
TI  - Cancer and cholesterol: understanding the V-shaped association in patients with
      diabetes.

PMID- 18725606
TI  - Concerns about health care warnings and their impact on prescribing behaviour.

PMID- 18725607
TI  - Fault/no fault part 2: uneasy bedfellows.

PMID- 18725608
TI  - Virtually better.

PMID- 18725609
TI  - Big pharma and good corporate citizenship.

PMID- 18725611
TI  - Novel changes proposed to United Kingdom's National Health Service.

PMID- 18725612
TI  - Four years later, roadblocks to AIDS drugs overcome.

PMID- 18725613
TI  - The intersection of faith, family and survival.

PMID- 18725614
TI  - Identifying unprovoked thromboembolism patients at low risk for recurrence who
      can discontinue anticoagulant therapy.
AB  - BACKGROUND: Whether to continue oral anticoagulant therapy beyond 6 months after
      an "unprovoked" venous thromboembolism is controversial. We sought to determine
      clinical predictors to identify patients who are at low risk of recurrent venous
      thromboembolism who could safely discontinue oral anticoagulants. METHODS: In a
      multicentre prospective cohort study, 646 participants with a first, unprovoked
      major venous thromboembolism were enrolled over a 4-year period. Of these, 600
      participants completed a mean 18-month follow-up in September 2006. We collected
      data for 69 potential predictors of recurrent venous thromboembolism while
      patients were taking oral anticoagulation therapy (5-7 months after initiation).
      During follow-up after discontinuing oral anticoagulation therapy, all episodes
      of suspected recurrent venous thromboembolism were independently adjudicated. We
      performed a multivariable analysis of predictor variables (p < 0.10) with high
      interobserver reliability to derive a clinical decision rule. RESULTS: We
      identified 91 confirmed episodes of recurrent venous thromboembolism during
      follow-up after discontinuing oral anticoagulation therapy (annual risk 9.3%, 95%
      CI 7.7%-11.3%). Men had a 13.7% (95% CI 10.8%-17.0%) annual risk. There was no
      combination of clinical predictors that satisfied our criteria for identifying a
      low-risk subgroup of men. Fifty-two percent of women had 0 or 1 of the following
      characteristics: hyperpigmentation, edema or redness of either leg; D-dimer > or
      = 250 microg/L while taking warfarin; body mass index > or = 30 kg/m(2); or age >
      or = 65 years. These women had an annual risk of 1.6% (95% CI 0.3%-4.6%). Women
      who had 2 or more of these findings had an annual risk of 14.1% (95% CI 10.9%
      17.3%). INTERPRETATION: Women with 0 or 1 risk factor may safely discontinue oral
      anticoagulant therapy after 6 months of therapy following a first unprovoked
      venous thromboembolism. This criterion does not apply to men.

PMID- 18725615
TI  - Independent associations between low-density lipoprotein cholesterol and cancer
      among patients with type 2 diabetes mellitus.
AB  - BACKGROUND: The risk association between low-density lipoprotein (LDL)
      cholesterol and cancer remains controversial and largely unexplored for people
      not receiving statin therapy. METHODS: We examined the risk association between
      LDL cholesterol and cancer among patients with type 2 diabetes mellitus who were
      free of cancer at enrolment and whose statin use was known. We considered a
      variety of nonlinear relationships in our analysis. RESULTS: During a median
      follow-up period of 4.90 years, cancer developed in 270 (4.4%) of 6107 patients.
      Among the 3800 patients who did not receive statin therapy, the risk association
      between LDL cholesterol and cancer was represented by a V-shaped curve. Compared
      with patients whose LDL cholesterol was at least 2.80 mmol/L but less than 3.80
      mmol/L, the risk of cancer, death from any cause or the composite outcome of
      cancer or death was greater among those with an LDL cholesterol level of less
      than 2.80 mmol/L (hazard ratio for cancer 1.74, 95% confidence interval [CI] 1.20
      2.52) and those with an LDL cholesterol level of 3.80 mmol/L or greater (hazard
      ratio for cancer 1.87, 95% CI 1.29-2.71). Using 3.8 mmol/L as a reference point,
      we found that the hazard ratio for cancer for every millimole per litre absolute
      change in LDL cholesterol was 1.54 (95% CI 1.19-1.99) among patients not using
      statins; the hazard ratio was reduced to 1.24 (1.01-1.53) for the entire sample
      (statin users and those not using statins). These associations persisted after
      adjustment for covariates and exclusion of patients with less than 2.5 years of
      follow-up. INTERPRETATION: Among patients with type 2 diabetes, the association
      between LDL cholesterol and cancer was V-shaped, whereby both low and high levels
      of LDL cholesterol were associated with elevated risk of cancer.

PMID- 18725616
TI  - Effect of regulatory warnings on antipsychotic prescription rates among elderly
      patients with dementia: a population-based time-series analysis.
AB  - BACKGROUND: Three warnings of serious adverse events associated with the use of
      atypical antipsychotic drugs among elderly patients with dementia were sent to
      health care professionals in Canada. We assessed the impact of these warnings on
      prescription rates of antipsychotic drugs in this patient population. METHODS: We
      used prescription drug claims data from Ontario to calculate prescription rates
      of atypical and conventional antipsychotic drugs among elderly patients with
      dementia from May 1, 2000, to Feb. 28, 2007. We performed a time-series analysis
      to estimate the effect of each warning on rates of antipsychotic drug use.
      RESULTS: Before the first warning, growth in the use of atypical antipsychotics
      was responsible for an increasing rate of overall antipsychotic use. Each warning
      was associated with a small relative decrease in the predicted growth in the use
      of atypical antipsychotic drugs: a 5.0% decrease after the first warning, 4.9%
      after the second and 3.2% after the third (each p < 0.05). The overall
      prescription rate of antipsychotic drugs among patients with dementia increased
      by 20%, from 1512 per 100 000 elderly patients in September 2002, the month
      before the first warning, to 1813 per 100 000 in February 2007, 20 months after
      the last warning. INTERPRETATION: Although the warnings slowed the growth in the
      use of atypical antipsychotic drugs among patients with dementia, they did not
      reduce the overall prescription rate of these potentially dangerous drugs. More
      effective interventions are necessary to improve postmarket drug safety in
      vulnerable populations.

PMID- 18725617
TI  - Heterochromia.
AB  - A patient was noted to have 2 different eye colours and miosis in her left eye.
      She ultimately received a diagnosis of congenital Horner syndrome. Determinants
      of eye colour and possible clinical significance are discussed.

PMID- 18725618
TI  - Testimonials versus evidence.

PMID- 18725620
TI  - The departure of death notices.

PMID- 18725621
TI  - Purple urine bag syndrome.

PMID- 18725622
TI  - Pertussis mortality and public misperceptions.

PMID- 18725623
TI  - Suppression of E-protein activity interferes with the development of BCR-ABL
      mediated myeloproliferative disease.
AB  - E-proteins are a class of helix-loop-helix (HLH) proteins, which play multiple
      roles throughout lymphoid development. The DNA binding activities of the E
      proteins are regulated by a distinct class of antagonistic HLH proteins, named
      Id1-4. Here we demonstrate that Id2 deficient mice in a C57BL/6 genetic
      background exhibit increased cellularity in the granulocyte/myeloid progenitor
      compartment and show significantly higher numbers of maturing neutrophils. Within
      6 months of age, Id2 deficient mice succumbed from overwhelming granulocytosis.
      The disease closely mimicked the distinctive features of human chronic myeloid
      leukemia: leukocytosis with maturing neutrophils, splenomegaly, hepatomegaly, and
      myeloid infiltration into peripheral tissues, including spleen, liver, and lungs.
      Strikingly, forced Id2 expression in murine bone marrow cells substantially
      delayed the onset of myeloproliferative disease (MPD). Collectively, these
      studies show that suppression of E-protein activity interferes with the
      development of BCR-ABL-mediated MPD.

PMID- 18725624
TI  - Flying in silence: Echolocating bats cease vocalizing to avoid sonar jamming.
AB  - Although it has been recognized that echolocating bats may experience jamming
      from the signals of conspecifics, research on this problem has focused
      exclusively on time-frequency adjustments in the emitted signals to minimize
      interference. Here, we report a surprising new strategy used by bats to avoid
      interference, namely silence. In a quantitative study of flight and vocal
      behavior of the big brown bat (Eptesicus fuscus), we discovered that the bat
      spends considerable time in silence when flying with conspecifics. Silent
      behavior, defined here as at least one bat in a pair ceasing vocalization for
      more than 0.2 s (200 ms), occurred as much as 76% of the time (mean of 40% across
      7 pairs) when their separation was shorter than 1 m, but only 0.08% when a single
      bat flew alone. Spatial separation, heading direction, and similarity in call
      design of paired bats were related to the prevalence of this silent behavior. Our
      data suggest that the bat uses silence as a strategy to avoid interference from
      sonar vocalizations of its neighbor, while listening to conspecific-generated
      acoustic signals to guide orientation. Based on previous neurophysiological
      studies of the bat's auditory midbrain, we hypothesize that environmental sounds
      (including vocalizations produced by other bats) and active echolocation evoke
      neural activity in different populations of neurons. Our findings offer
      compelling evidence that the echolocating bat switches between active and passive
      sensing to cope with a complex acoustic environment, and these results hold broad
      implications for research on navigation and communication throughout the animal
      kingdom.

PMID- 18725625
TI  - Synthetic glycopeptide vaccines combining beta-mannan and peptide epitopes induce
      protection against candidiasis.
AB  - The first fully synthetic glycopeptide vaccines against a fungal disease have
      been used to combat disseminated candidiasis in mice. Six T cell peptides found
      in Candida albicans cell wall proteins were selected by algorithm peptide epitope
      searches; each was synthesized and conjugated to the fungal cell wall beta-mannan
      trisaccharide [beta-(Man)(3)] by novel saccharide-peptide linker chemistry to
      create glycopeptide conjugates. The six proteins were selected because of
      expression during human candidiasis and cell wall association and included:
      fructose-bisphosphate aldolase (Fba); methyltetrahydropteroyltriglutamate (Met6);
      hyphal wall protein-1 (Hwp1); enolase (Enol); glyceraldehyde-3-phosphate
      dehydrogenase (Gap1); and phosphoglycerate kinase (Pgk1). By immunization
      protocols favoring production of protective antibody, the beta-(Man)(3)-Fba, beta
      (Man)(3)-Met6 and beta-(Man)(3)-Hwp1 induced protection evidenced by survival and
      reduced kidney fungal burden, the beta-(Man)(3)-Eno1 and beta-(Man)(3)-Gap1 gave
      moderate protection, and the beta-(Man)(3)-Pgk1 slightly enhanced disease. For
      the beta-(Man)(3)-Fba conjugate, protection was uniquely acquired through
      immunity against the carbohydrate and the Fba peptide. This approach based on
      fully synthetic chemically defined immunogens should be generally useful in
      vaccine development.

PMID- 18725626
TI  - Heparin promotes the growth of human embryonic stem cells in a defined serum-free
      medium.
AB  - A major limitation in developing applications for the use of human embryonic stem
      cells (HESCs) is our lack of knowledge of their responses to specific cues that
      control self-renewal, differentiation, and lineage selection. HESCs are most
      commonly maintained on inactivated mouse embryonic fibroblast feeders in medium
      supplemented with FCS, or proprietary replacements such as knockout serum
      replacement together with FGF-2. These undefined culture conditions hamper
      analysis of the mechanisms that control HESC behavior. We have now developed a
      defined serum-free medium, hESF9, for the culture of HESCs on a type I-collagen
      substrate without feeders. In contrast to other reported media for the culture of
      HESCs, this medium has a lower osmolarity (292 mosmol/liter), l-ascorbic acid-2
      phosphate (0.1 microg/ml), and heparin. Insulin, transferrin, albumin conjugated
      with oleic acid, and FGF-2 (10 ng/ml) were the only protein components. Further,
      we found that HESCs would proliferate in the absence of exogenous FGF-2 if
      heparin was also present. However, their growth was enhanced by the addition of
      FGF-2 up to 10 ng/ml although higher concentrations were deleterious in the
      presence of heparin.

PMID- 18725627
TI  - Surfen, a small molecule antagonist of heparan sulfate.
AB  - In a search for small molecule antagonists of heparan sulfate, we examined the
      activity of bis-2-methyl-4-amino-quinolyl-6-carbamide, also known as surfen.
      Fluorescence-based titrations indicated that surfen bound to glycosaminoglycans,
      and the extent of binding increased according to charge density in the order
      heparin > dermatan sulfate > heparan sulfate > chondroitin sulfate. All charged
      groups in heparin (N-sulfates, O-sulfates, and carboxyl groups) contributed to
      binding, consistent with the idea that surfen interacted electrostatically.
      Surfen neutralized the anticoagulant activity of both unfractionated and low
      molecular weight heparins and inhibited enzymatic sulfation and degradation
      reactions in vitro. Addition of surfen to cultured cells blocked FGF2-binding and
      signaling that depended on cell surface heparan sulfate and prevented both FGF2-
      and VEGF(165)-mediated sprouting of endothelial cells in Matrigel. Surfen also
      blocked heparan sulfate-mediated cell adhesion to the Hep-II domain of
      fibronectin and prevented infection by HSV-1 that depended on glycoprotein D
      interaction with heparan sulfate. These findings demonstrate the feasibility of
      identifying small molecule antagonists of heparan sulfate and raise the
      possibility of developing pharmacological agents to treat disorders that involve
      glycosaminoglycan-protein interactions.

PMID- 18725628
TI  - Dynamics of ligand substitution in labile cobalt complexes resolved by ultrafast
      T-jump.
AB  - Ligand exchange of hydrated metal complexes is common in chemical and biological
      systems. Using the ultrafast T-jump, we examined this process, specifically the
      transformation of aqua cobalt (II) complexes to their fully halogenated species.
      The results reveal a stepwise mechanism with time scales varying from hundreds of
      picoseconds to nanoseconds. The dynamics are significantly faster when the
      structure is retained but becomes rate-limited when the octahedral-to-tetrahedral
      structural change bottlenecks the transformation. Evidence is presented, from
      bimolecular kinetics and energetics (enthalpic and entropic), for a reaction in
      which the ligand assists the displacement of water molecules, with the retention
      of the entering ligand in the activated state. The reaction time scale deviates
      by one to two orders of magnitude from that of ionic diffusion, suggesting the
      involvement of a collisional barrier between the ion and the much larger complex.

PMID- 18725629
TI  - Magnetic alignment in grazing and resting cattle and deer.
AB  - We demonstrate by means of simple, noninvasive methods (analysis of satellite
      images, field observations, and measuring "deer beds" in snow) that domestic
      cattle (n = 8,510 in 308 pastures) across the globe, and grazing and resting red
      and roe deer (n = 2,974 at 241 localities), align their body axes in roughly a
      north-south direction. Direct observations of roe deer revealed that animals
      orient their heads northward when grazing or resting. Amazingly, this ubiquitous
      phenomenon does not seem to have been noticed by herdsmen, ranchers, or hunters.
      Because wind and light conditions could be excluded as a common denominator
      determining the body axis orientation, magnetic alignment is the most
      parsimonious explanation. To test the hypothesis that cattle orient their body
      axes along the field lines of the Earth's magnetic field, we analyzed the body
      orientation of cattle from localities with high magnetic declination. Here,
      magnetic north was a better predictor than geographic north. This study reveals
      the magnetic alignment in large mammals based on statistically sufficient sample
      sizes. Our findings open horizons for the study of magnetoreception in general
      and are of potential significance for applied ethology (husbandry, animal
      welfare). They challenge neuroscientists and biophysics to explain the proximate
      mechanisms.

PMID- 18725630
TI  - Psychologically induced cooling of a specific body part caused by the illusory
      ownership of an artificial counterpart.
AB  - The sense of body ownership represents a fundamental aspect of our self
      awareness, but is disrupted in many neurological, psychiatric, and psychological
      conditions that are also characterized by disruption of skin temperature
      regulation, sometimes in a single limb. We hypothesized that skin temperature in
      a specific limb could be disrupted by psychologically disrupting the sense of
      ownership of that limb. In six separate experiments, and by using an established
      protocol to induce the rubber hand illusion, we demonstrate that skin temperature
      of the real hand decreases when we take ownership of an artificial counterpart.
      The decrease in skin temperature is limb-specific: it does not occur in the
      unstimulated hand, nor in the ipsilateral foot. The effect is not evoked by
      tactile or visual input per se, nor by simultaneous tactile and visual input per
      se, nor by a shift in attention toward the experimental side or limb. In fact,
      taking ownership of an artificial hand slows tactile processing of information
      from the real hand, which is also observed in patients who demonstrate body
      disownership after stroke. These findings of psychologically induced limb
      specific disruption of temperature regulation provide the first evidence that:
      taking ownership of an artificial body part has consequences for the real body
      part; that the awareness of our physical self and the physiological regulation of
      self are closely linked in a top-down manner; and that cognitive processes that
      disrupt the sense of body ownership may in turn disrupt temperature regulation in
      numerous states characterized by both.

PMID- 18725631
TI  - Global alignment of multiple protein interaction networks with application to
      functional orthology detection.
AB  - Protein-protein interactions (PPIs) and their networks play a central role in all
      biological processes. Akin to the complete sequencing of genomes and their
      comparative analysis, complete descriptions of interactomes and their comparative
      analysis is fundamental to a deeper understanding of biological processes. A
      first step in such an analysis is to align two or more PPI networks. Here, we
      introduce an algorithm, IsoRank, for global alignment of multiple PPI networks.
      The guiding intuition here is that a protein in one PPI network is a good match
      for a protein in another network if their respective sequences and neighborhood
      topologies are a good match. We encode this intuition as an eigenvalue problem in
      a manner analogous to Google's PageRank method. Using IsoRank, we compute a
      global alignment of the Saccharomyces cerevisiae, Drosophila melanogaster,
      Caenorhabditis elegans, Mus musculus, and Homo sapiens PPI networks. We
      demonstrate that incorporating PPI data in ortholog prediction results in
      improvements over existing sequence-only approaches and over predictions from
      local alignments of the yeast and fly networks. Previous methods have been
      effective at identifying conserved, localized network patterns across pairs of
      networks. This work takes the further step of performing a global alignment of
      multiple PPI networks. It simultaneously uses sequence similarity and network
      data and, unlike previous approaches, explicitly models the tradeoff inherent in
      combining them. We expect IsoRank-with its simultaneous handling of node
      similarity and network similarity-to be applicable across many scientific
      domains.

PMID- 18725632
TI  - Mating induces an immune response and developmental switch in the Drosophila
      oviduct.
AB  - Mating triggers physiological and behavioral changes in females. To understand
      how females effect these changes, we used microarray, proteomic, and comparative
      analyses to characterize gene expression in oviducts of mated and unmated
      Drosophila females. The transition from non-egg laying to egg laying elicits a
      distinct molecular profile in the oviduct. Immune-related transcripts and
      proteins involved in muscle and polarized epithelial function increase, whereas
      cell growth and differentiation-related genes are down-regulated. Our combined
      results indicate that mating triggers molecular and biochemical changes that
      mediate progression from a "poised" state to a mature, functional stage.

PMID- 18725633
TI  - Electron injection into organic semiconductor devices from high work function
      cathodes.
AB  - We show that polymer light-emitting diodes with high work-function cathodes and
      conjugated polyelectrolyte injection/transport layers exhibit excellent
      efficiencies despite large electron-injection barriers. Correlation of device
      response times with structure provides evidence that the electron-injection
      mechanism involves redistribution of the ions within the polyelectrolyte electron
      transport layer and hole accumulation at the interface between the emissive and
      electron-transport layers. Both processes lead to screening of the internal
      electric field and a lowering of the electron-injection barrier. The hole and
      electron currents are therefore diffusion currents rather than drift currents.
      The response time and the device performance are influenced by the type of
      counterion used.

PMID- 18725634
TI  - Inhibition of the fungal fatty acid synthase type I multienzyme complex.
AB  - Fatty acids are among the major building blocks of living cells, making lipid
      biosynthesis a potent target for compounds with antibiotic or antineoplastic
      properties. We present the crystal structure of the 2.6-MDa Saccharomyces
      cerevisiae fatty acid synthase (FAS) multienzyme in complex with the antibiotic
      cerulenin, representing, to our knowledge, the first structure of an inhibited
      fatty acid megasynthase. Cerulenin attacks the FAS ketoacyl synthase (KS) domain,
      forming a covalent bond to the active site cysteine C1305. The inhibitor binding
      causes two significant conformational changes of the enzyme. First, phenylalanine
      F1646, shielding the active site, flips and allows access to the nucleophilic
      cysteine. Second, methionine M1251, placed in the center of the acyl-binding
      tunnel, rotates and unlocks the inner part of the fatty acid binding cavity. The
      importance of the rotational movement of the gatekeeping M1251 side chain is
      reflected by the cerulenin resistance and the changed product spectrum reported
      for S. cerevisiae strains mutated in the adjacent glycine G1250. Platensimycin
      and thiolactomycin are two other potent inhibitors of KSs. However, in contrast
      to cerulenin, they show selectivity toward the prokaryotic FAS system. Because
      the flipped F1646 characterizes the catalytic state accessible for platensimycin
      and thiolactomycin binding, we superimposed structures of inhibited bacterial
      enzymes onto the S. cerevisiae FAS model. Although almost all side chains
      involved in inhibitor binding are conserved in the FAS multienzyme, a different
      conformation of the loop K1413-K1423 of the KS domain might explain the observed
      low antifungal properties of platensimycin and thiolactomycin.

PMID- 18725635
TI  - Neural correlates of partial lexical activation.
AB  - As a spoken word unfolds over time, it is temporarily consistent with the
      acoustic forms of multiple words. Previous behavioral research has shown that, in
      the face of temporary ambiguity about how a word will end, multiple candidate
      words are briefly activated. Here, we provide neural imaging evidence that
      lexical candidates only temporarily consistent with the input activate
      perceptually based semantic representations. An artificial lexicon and novel
      visual environment were used to target human MT/V5 and an area anterior to it
      which have been shown to be recruited during the reading of motion words.
      Participants learned words that referred to novel objects and to motion or
      color/texture changes that the objects underwent. The lexical items corresponding
      to the change events were organized into phonologically similar pairs differing
      only in the final syllable. Upon hearing spoken scene descriptions in a
      posttraining verification task, participants showed greater activation in the
      left hemisphere anterior extent of MT/V5 when motion words were heard than when
      nonmotion words were heard. Importantly, when a nonmotion word was heard, the
      level of activation in the anterior extent of MT/V5 was modulated by whether
      there was a phonologically related competitor that was a motion word rather than
      another nonmotion word. These results provide evidence of activation of a
      perceptual brain region in response to the semantics of a word while lexical
      competition is in process and before the word is fully recognized.

PMID- 18725636
TI  - Formation of gullies on Mars: link to recent climate history and insolation
      microenvironments implicate surface water flow origin.
AB  - Features seen in portions of a typical midlatitude Martian impact crater show
      that gully formation follows a geologically recent period of midlatitude
      glaciation. Geological evidence indicates that, in the relatively recent past,
      sufficient snow and ice accumulated on the pole-facing crater wall to cause
      glacial flow and filling of the crater floor with debris-covered glaciers. As
      glaciation waned, debris-covered glaciers ceased flowing, accumulation zones lost
      ice, and newly exposed wall alcoves continued as the location for limited
      snow/frost deposition, entrapment, and preservation. Analysis of the insolation
      geometry of this pole-facing crater wall, and similar occurrences in other
      craters at these latitudes on Mars, shows that they are uniquely favored for
      accumulation of snow and ice, and a relatively more rapid exposure to warmer
      summer temperatures. We show that, after the last glaciation, melting of residual
      snow and ice in alcoves could have formed the fluvial channels and sedimentary
      fans of the gullies. Recent modeling shows that top-down melting can occur in
      these microenvironments under conditions similar to those currently observed on
      Mars, if small amounts of snow or frost accumulate in alcoves and channels.
      Accumulation and melting is even more favored in the somewhat wetter, relatively
      recent geological past of Mars, after the period of active glaciation.

PMID- 18725637
TI  - Navigating networks by using homophily and degree.
AB  - Many large distributed systems can be characterized as networks where short paths
      exist between nearly every pair of nodes. These include social, biological,
      communication, and distribution networks, which often display power-law or small
      world structure. A central challenge of distributed systems is directing messages
      to specific nodes through a sequence of decisions made by individual nodes
      without global knowledge of the network. We present a probabilistic analysis of
      this navigation problem that produces a surprisingly simple and effective method
      for directing messages. This method requires calculating only the product of the
      two measures widely used to summarize all local information. It outperforms prior
      approaches reported in the literature by a large margin, and it provides a formal
      model that may describe how humans make decisions in sociological studies
      intended to explore the social network as well as how they make decisions in more
      naturalistic settings.

PMID- 18725638
TI  - Both maltose-binding protein and ATP are required for nucleotide-binding domain
      closure in the intact maltose ABC transporter.
AB  - The maltose transporter MalFGK(2) of Escherichia coli is a member of the ATP
      binding cassette superfamily. A periplasmic maltose-binding protein (MBP)
      delivers maltose to MalFGK(2) and stimulates its ATPase activity. Site-directed
      spin labeling EPR spectroscopy was used to study the opening and closing of the
      nucleotide-binding interface of MalFGK(2) during the catalytic cycle. In the
      intact transporter, closure of the interface coincides not just with the binding
      of ATP, as seen with isolated nucleotide-binding domains, but requires both MBP
      and ATP, implying that MBP stimulates ATPase activity by promoting the closure of
      the nucleotide-binding interface. After ATP hydrolysis, with MgADP and MBP bound,
      the nucleotide-binding interface resides in a semi-open configuration distinct
      from the fully open configuration seen in the absence of any ligand. We propose
      that P(i) release coincides with the reorientation of transmembrane helices to an
      inward-facing conformation and the final step of maltose translocation into the
      cell.

PMID- 18725639
TI  - RID1, encoding a Cys2/His2-type zinc finger transcription factor, acts as a
      master switch from vegetative to floral development in rice.
AB  - Transition from the vegetative phase to reproductive phase is a crucial process
      in the life cycle of higher plants. Although the molecular mechanisms of
      flowering regulation have been extensively characterized in a number of plant
      species, little is known regarding how the transition process initiates. Here, we
      show that the Rice Indeterminate 1 (RID1) gene acts as the master switch for the
      transition from the vegetative to reproductive phase. RID1 encodes a Cys-2/His-2
      type zinc finger transcription factor that does not have an ortholog in
      Arabidopsis spp. A RID1 knockout (rid1), mutated by T-DNA insertion, never headed
      after growing for >500 days under a range of growth conditions and is thus
      referred to as a never-flowering phenotype. This mutation-suppressed expression
      of the genes is known to be involved in flowering regulation, especially in the
      Ehd1/Hd3a pathway and a series of RFT homologs. RID1 seems to be independent of
      the circadian clock. A model was proposed to place RID1 in the molecular pathways
      of flowering regulation in rice, for which there are two indispensable elements.
      In the first, RID1 is controlling the phase transition and initiation of floral
      induction. In the other, the Hd3a/RFL1/FTL complex acts as the immediate inducer
      of flowering. Loss of function in either element would cause never-flowering.
      Once the phase transition is induced with the activation of RID1, flowering
      signal is transduced and regulated through the various pathways and eventually
      integrated with FT-like proteins to induce flowering.

PMID- 18725640
TI  - Efficient reproduction of cynomolgus monkey using pronuclear embryo transfer
      technique.
AB  - One of the technical bottlenecks in producing nonhuman primate models is that
      current assisted reproductive techniques, such as in vitro culture and frozen
      conservation of multicell-stage embryos, often result in poor embryo quality and
      subsequently lead to low birth rates. We investigated whether pronuclear embryo
      transfer can be used as an effective means for improving pregnancy and live birth
      rates of nonhuman primates. We collected 174 metaphase II oocytes by laparoscopy
      from 22 superovulated mature females and then fertilized these eggs using either
      in vitro fertilization or intracytoplasmic sperm injection, resulting in a 33.3%
      and a 50% fertilization rate, respectively. These 66 fertilized pronuclear-stage
      embryos were then tubally transferred to 30 recipients and led to 7 births and 1
      abortion. Importantly, we observed that the highest live birth rate of
      approximately 64% was obtained when the transfer of pronuclear embryos was
      performed in the presence of new corpus luteum in the ovary of recipients between
      24 h and 36 h after estradiol peak. Therefore, our experiments demonstrate that
      by matching the critical time window in the recipient's reproductive cycle for
      achieving optimal embryo-uterine synchrony, pronuclear embryo transfer technology
      can significantly improve the pregnancy rate and live birth of healthy baby
      monkeys. This efficient method should be valuable to the systematic efforts in
      construction of various transgenic primate disease models.

PMID- 18725641
TI  - Recent climate extremes alter alpine lake ecosystems.
AB  - Here, we show that alpine lake ecosystems are responsive to interannual variation
      in climate, based on long-term limnological and meteorological data from the
      Canadian Rockies. In the 2000s, in years with colder winter temperatures, higher
      winter snowfall, later snowmelt, shorter ice-free seasons, and dryer summers,
      relative to the 1990s, alpine lakes became clearer, warmer, and mixed to deeper
      depths. Further, lakes became more dilute and nutrient-poor, the latter leading
      to significant declines in total phytoplankton biomass. However, increased
      concentrations of dissolved organic carbon in lake water stimulated the
      appearance of small mixotrophic algal species, partially offsetting the decline
      in autotrophic phytoplankton biomass and increasing algal species richness. The
      climate regime in the 2000s altered the physical, chemical, and biological
      character and the function of high-elevation aquatic ecosystems. Forecasts of
      increased climatic variability in the future pose serious ramifications for both
      the biodiversity and ecosystem function of high-elevation lakes.

PMID- 18725642
TI  - Increasing cloning possibilities using artificial zinc finger nucleases.
AB  - The ability to accurately digest and ligate DNA molecules of different origins is
      fundamental to modern recombinant DNA research. Only a handful of enzymes are
      capable of recognizing and cleaving novel and long DNA sequences, however. The
      slow evolution and engineering of new restriction enzymes calls for alternative
      strategies to design novel and unique restriction enzymes capable of binding and
      digesting specific long DNA sequences. Here we report on the use of zinc finger
      nucleases (ZFNs)-hybrid synthetic restriction enzymes that can be specifically
      designed to bind and cleave long DNA sequences-for the purpose of DNA
      recombination. We show that novel ZFNs can be designed for the digestion of
      specific sequences and can be expressed and used for cloning purposes. We also
      demonstrate the power of ZFNs in DNA cloning by custom-cloning a target DNA
      sequence and assembling dual-expression cassettes on a single target plasmid, a
      task that rarely can be achieved using type-II restriction enzymes. We
      demonstrate the flexibility of ZFN design and the ability to shuffle monomers of
      different ZFNs for the digestion of compatible recognition sites through ligation
      of compatible ends and their cleavage by heterodimer ZFNs. Of no less importance,
      we show that ZFNs can be designed to recognize and cleave existing DNA sequences
      for the custom-cloning of native target DNA molecules.

PMID- 18725643
TI  - Lignin degradation in wood-feeding insects.
AB  - The aromatic polymer lignin protects plants from most forms of microbial attack.
      Despite the fact that a significant fraction of all lignocellulose degraded
      passes through arthropod guts, the fate of lignin in these systems is not known.
      Using tetramethylammonium hydroxide thermochemolysis, we show lignin degradation
      by two insect species, the Asian longhorned beetle (Anoplophora glabripennis) and
      the Pacific dampwood termite (Zootermopsis angusticollis). In both the beetle and
      termite, significant levels of propyl side-chain oxidation (depolymerization) and
      demethylation of ring methoxyl groups is detected; for the termite, ring
      hydroxylation is also observed. In addition, culture-independent fungal gut
      community analysis of A. glabripennis identified a single species of fungus in
      the Fusarium solani/Nectria haematococca species complex. This is a soft-rot
      fungus that may be contributing to wood degradation. These results transform our
      understanding of lignin degradation by wood-feeding insects.

PMID- 18725644
TI  - Structural basis for suppression of a host antiviral response by influenza A
      virus.
AB  - Influenza A viruses are responsible for seasonal epidemics and high mortality
      pandemics. A major function of the viral NS1A protein, a virulence factor, is the
      inhibition of the production of IFN-beta mRNA and other antiviral mRNAs. The NS1A
      protein of the human influenza A/Udorn/72 (Ud) virus inhibits the production of
      these antiviral mRNAs by binding the cellular 30-kDa subunit of the cleavage and
      polyadenylation specificity factor (CPSF30), which is required for the 3' end
      processing of all cellular pre-mRNAs. Here we report the 1.95-A resolution X-ray
      crystal structure of the complex formed between the second and third zinc finger
      domain (F2F3) of CPSF30 and the C-terminal domain of the Ud NS1A protein. The
      complex is a tetramer, in which each of two F2F3 molecules wraps around two NS1A
      effector domains that interact with each other head-to-head. This structure
      identifies a CPSF30 binding pocket on NS1A comprised of amino acid residues that
      are highly conserved among human influenza A viruses. Single amino acid changes
      within this binding pocket eliminate CPSF30 binding, and a recombinant Ud virus
      expressing an NS1A protein with such a substitution is attenuated and does not
      inhibit IFN-beta pre-mRNA processing. This binding pocket is a potential target
      for antiviral drug development. The crystal structure also reveals that two amino
      acids outside of this pocket, F103 and M106, which are highly conserved (>99%)
      among influenza A viruses isolated from humans, participate in key hydrophobic
      interactions with F2F3 that stabilize the complex.

PMID- 18725646
TI  - Endocrine therapy and bone loss in breast cancer: time to close in the RANK(L)?

PMID- 18725645
TI  - Actin-binding cleft closure in myosin II probed by site-directed spin labeling
      and pulsed EPR.
AB  - We present a structurally dynamic model for nucleotide- and actin-induced closure
      of the actin-binding cleft of myosin, based on site-directed spin labeling and
      electron paramagnetic resonance (EPR) in Dictyostelium myosin II. The actin
      binding cleft is a solvent-filled cavity that extends to the nucleotide-binding
      pocket and has been predicted to close upon strong actin binding. Single-cysteine
      labeling sites were engineered to probe mobility and accessibility within the
      cleft. Addition of ADP and vanadate, which traps the posthydrolysis biochemical
      state, influenced probe mobility and accessibility slightly, whereas actin
      binding caused more dramatic changes in accessibility, consistent with cleft
      closure. We engineered five pairs of cysteine labeling sites to straddle the
      cleft, each pair having one label on the upper 50-kDa domain and one on the lower
      50-kDa domain. Distances between spin-labeled sites were determined from the
      resulting spin-spin interactions, as measured by continuous wave EPR for
      distances of 0.7-2 nm or pulsed EPR (double electron-electron resonance) for
      distances of 1.7-6 nm. Because of the high distance resolution of EPR, at least
      two distinct structural states of the cleft were resolved. Each of the
      biochemical states tested (prehydrolysis, posthydrolysis, and rigor), reflects a
      mixture of these structural states, indicating that the coupling between
      biochemical and structural states is not rigid. The resulting model is much more
      dynamic than previously envisioned, with both open and closed conformations of
      the cleft interconverting, even in the rigor actomyosin complex.

PMID- 18725647
TI  - Cerebrovascular disease risk in older head and neck cancer patients after
      radiotherapy.
AB  - PURPOSE: Cerebrovascular disease is common in head and neck cancer patients, but
      it is unknown whether radiotherapy increases the cerebrovascular disease risk in
      this population. PATIENTS AND METHODS: We identified 6,862 patients (age > 65
      years) from the Surveillance, Epidemiology, and End Results (SEER) -Medicare
      cohort diagnosed with nonmetastatic head and neck cancer between 1992 and 2002.
      Using proportional hazards regression, we compared risk of cerebrovascular events
      (stroke, carotid revascularization, or stroke death) after treatment with
      radiotherapy alone, surgery plus radiotherapy, or surgery alone. To further
      validate whether treatment groups had equivalent baseline risk of vascular
      disease, we compared the risks of developing a control diagnosis, cardiac events
      (myocardial infarction, percutaneous coronary intervention, coronary artery
      bypass graft, or cardiac death). Unlike cerebrovascular risk, no difference in
      cardiac risk was hypothesized. RESULTS: Mean age was 76 +/- 7 years. Ten-year
      incidence of cerebrovascular events was 34% in patients treated with radiotherapy
      alone compared with 25% in patients treated with surgery plus radiotherapy and
      26% in patients treated with surgery alone (P < .001). After adjusting for
      covariates, patients treated with radiotherapy alone had increased
      cerebrovascular risk compared with surgery plus radiotherapy (hazard ratio [HR] =
      1.42; 95% CI, 1.14 to 1.77) and surgery alone (HR = 1.50; 95% CI, 1.18 to 1.90).
      However, no difference was found for surgery plus radiotherapy versus surgery
      alone (P = .60). As expected, patients treated with radiotherapy alone had no
      increased cardiac risk compared with the other treatment groups (P = .63 and P =
      .81). CONCLUSION: Definitive radiotherapy for head and neck cancer, but not
      postoperative radiotherapy, was associated with excess cerebrovascular disease
      risk in older patients.

PMID- 18725648
TI  - Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors
      for nonmetastatic breast cancer.
AB  - PURPOSE: Adjuvant aromatase inhibitor therapy is well established in
      postmenopausal women with hormone receptor-positive breast cancer, but such
      therapy is complicated by accelerated bone loss and increased fracture risk. We
      investigated the ability of denosumab, a fully human monoclonal antibody against
      receptor activator of nuclear factor-kappaB ligand, to protect against aromatase
      inhibitor-induced bone loss. PATIENTS AND METHODS: Eligible women with hormone
      receptor-positive nonmetastatic breast cancer treated with adjuvant aromatase
      inhibitor therapy were stratified by duration of aromatase inhibitor therapy (<
      or = 6 v > 6 months), received supplemental calcium and vitamin D, and were
      randomly assigned to receive placebo (n = 125) or subcutaneous denosumab 60 mg (n
      = 127) every 6 months. At enrollment, all patients were required to have evidence
      of low bone mass, excluding osteoporosis. The primary end point was percentage
      change from baseline at month 12 in lumbar spine bone mineral density (BMD).
      RESULTS: At 12 and 24 months, lumbar spine BMD increased by 5.5% and 7.6%,
      respectively, in the denosumab group versus placebo (P < .0001 at both time
      points). Increases were observed as early as 1 month and were not influenced by
      duration of aromatase inhibitor therapy. Increases in BMD were also observed at
      the total hip, total body, femoral neck, and the predominantly cortical one-third
      radius. Bone turnover markers decreased with denosumab treatment. Overall
      incidence of treatment-emergent adverse events (AEs) was similar between
      treatment groups. CONCLUSION: In women with nonmetastatic breast cancer and low
      bone mass who were receiving adjuvant aromatase inhibitor therapy, twice-yearly
      administration of denosumab led to significant increases in BMD over 24 months at
      trabecular and cortical bone, with overall AE rates similar to those of placebo.

PMID- 18725649
TI  - Trends in survival over the past two decades among white and black patients with
      newly diagnosed stage IV breast cancer.
AB  - PURPOSE: Overall, breast cancer mortality has been declining in the United
      States, but survival studies of patients with stage IV disease are limited. The
      aim of this study was to evaluate trends in and factors affecting survival in a
      large population-based cohort of patients with newly diagnosed stage IV breast
      cancer. PATIENTS AND METHODS: We searched the Surveillance, Epidemiology, and End
      Results registry to identify female patients with stage IV breast cancer
      diagnosed between 1988 and 2003. Patients were divided into three groups
      according to year of diagnosis (1988 to 1993, 1994 to 1998, and 1999 to 2003).
      Survival outcomes were estimated by the Kaplan-Meier method, and Cox models were
      fit to determine the characteristics independently associated with survival.
      RESULTS: We identified 15,438 patients. Median age was 62 years. Median follow-up
      was 16 months, 18 months, and 11 months in periods 1988 to 1993, 1994 to 1998,
      and 1999 to 2003, respectively. Median breast cancer-specific survival was 23
      months. In the multivariate model, earlier year of diagnosis, grade 3 disease,
      increasing age, being unmarried, hormone receptor-negative disease, and no
      surgery were all independently associated with worse overall and breast cancer
      specific survival. With each successive year of diagnosis, black patients had an
      increasingly greater risk of death compared with white patients (hazard ratio,
      1.03; 95% CI, 1.00 to 1.06; P = .031). CONCLUSION: The survival of patients with
      newly diagnosed stage IV breast cancer has modestly improved over time, but these
      data suggest that the disparity in survival between black and white patients has
      increased.

PMID- 18725650
TI  - Force measurements on the posterior oblique ligament and superficial medial
      collateral ligament proximal and distal divisions to applied loads.
AB  - BACKGROUND: There is limited information regarding load responses of the
      posterior oblique and superficial medial collateral ligaments to applied loads.
      HYPOTHESES: The degree of knee flexion affects loads experienced by the posterior
      oblique ligament and both divisions of the superficial medial collateral
      ligament. The posterior oblique ligament provides significant resistance to
      valgus and internal rotation forces near knee extension. Different load responses
      are experienced by proximal and distal divisions of the superficial medial
      collateral ligament. STUDY DESIGN: Descriptive laboratory study. METHODS: Twenty
      four nonpaired, fresh-frozen cadaveric knees were tested. Buckle transducers were
      applied to the proximal and distal divisions of the superficial medial collateral
      and posterior oblique ligaments. Applied loads at 0 degrees, 20 degrees, 30
      degrees, 60 degrees, and 90 degrees of knee flexion consisted of 10 N m valgus
      loads, 5 N.m internal and external rotation torques, and 88 N anterior and
      posterior drawer loads. RESULTS: External rotation torques produced a
      significantly higher load response on the distal superficial medial collateral
      ligament than did internal rotation torques at all flexion angles with the
      largest difference at 90 degrees (96.6 vs 22.5 N). For an applied valgus load at
      60 degrees of knee flexion, loads on the superficial medial collateral ligament
      were significantly higher in the distal division (103.5 N) than the proximal
      division (71.9 N). The valgus load response of the posterior oblique ligament at
      0 degrees of flexion (19.1 N) was significantly higher than at 30 degrees (10.6
      N), 60 degrees (7.8 N), and 90 degrees (6.8 N) of flexion. At 0 degrees of knee
      flexion, the load response to internal rotation on the posterior oblique ligament
      (45.8 N) was significantly larger than was the response on both divisions of the
      superficial medial collateral ligament (20 N for both divisions). At 90 degrees
      of flexion, the load response to internal rotation torques reciprocated between
      these structures with a significantly higher response in the distal superficial
      medial collateral ligament division (22.5 N) than the posterior oblique ligament
      (9.1 N). CONCLUSION: The superficial medial collateral ligament experienced the
      largest load response to applied valgus and external rotation torques; the
      posterior oblique ligament observed the highest load response to internal
      rotation near extension. CLINICAL RELEVANCE: This study provides new knowledge of
      the individual biomechanical function of the main medial knee structures in an
      intact knee and will assist in the interpretation of clinical knee motion testing
      and provide evidence for techniques involving repair or reconstruction of the
      posterior oblique ligament and both divisions of the superficial medial
      collateral ligament.

PMID- 18725651
TI  - Improved muscle healing after contusion injury by the inhibitory effect of
      suramin on myostatin, a negative regulator of muscle growth.
AB  - BACKGROUND: Muscle contusions are the most common muscle injuries in sports
      medicine. Although these injuries are capable of healing, incomplete functional
      recovery often occurs. HYPOTHESIS: Suramin enhances muscle healing by both
      stimulating muscle regeneration and preventing fibrosis in contused skeletal
      muscle. STUDY DESIGN: Controlled laboratory study. METHODS: In vitro: Myoblasts
      (C2C12 cells) and muscle-derived stem cells (MDSCs) were cultured with suramin,
      and the potential of suramin to induce their differentiation was evaluated.
      Furthermore, MDSCs were cocultured with suramin and myostatin (MSTN) to monitor
      the capability of suramin to neutralize the effect of MSTN. In vivo: Varying
      concentrations of suramin were injected in the tibialis anterior muscle of mice 2
      weeks after muscle contusion injury. Muscle regeneration and scar tissue
      formation were evaluated by histologic analysis and functional recovery was
      measured by physiologic testing RESULTS: In vitro: Suramin stimulated the
      differentiation of myoblasts and MDSCs in a dose-dependent manner. Moreover,
      suramin neutralized the inhibitory effect of MSTN on MDSC differentiation. In
      vivo: Suramin treatment significantly promoted muscle regeneration, decreased
      fibrosis formation, reduced myostatin expression in injured muscle, and increased
      muscle strength after contusion injury. CONCLUSION: Intramuscular injection of
      suramin after a contusion injury improved overall skeletal muscle healing.
      Suramin enhanced myoblast and MDSC differentiation and neutralized MSTN's
      negative effect on myogenic differentiation in vitro, which suggests a possible
      mechanism for the beneficial effects that this pharmacologic agent exhibits in
      vivo. CLINICAL RELEVANCE: These findings could contribute to the development of
      biological treatments to aid in muscle healing after experiencing a muscle
      injury.

PMID- 18725652
TI  - Incidence of associated injuries with acute acromioclavicular joint dislocations
      types III through V.
AB  - BACKGROUND: Traumatic acromioclavicular (AC) joint dislocations are common
      injuries among the active population. The injury mechanism requires excessive
      force delivered by a fall or blow to the shoulder. Associated injuries may occur
      and remain undetected if they are masked by the painful and prominent AC joint
      injury. HYPOTHESIS: Intra-articular injuries associated with high-grade AC joint
      dislocations are common. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: Between 2002 and 2007, 77 patients (68 male, 9 female; average age, 35.5
      years; range, 17-62 years) were surgically treated for acute AC joint
      dislocations (Rockwood type III, 5; type IV, 30; and type V, 42). All patients
      underwent diagnostic glenohumeral joint arthroscopy. Concomitant intra-articular
      injuries were identified and treated. RESULTS: Intra-articular injuries were
      found in 14 of 77 patients (18.2%). Superior labral anterior posterior (SLAP)
      lesions were observed in 11 of 77 patients 14.3% (SLAP I, 3; II, 2; III, 3; and
      IV, 3). Nineteen percent of Rockwood V lesions had associated SLAP lesions (SLAP
      I excluded), whereas only 3.4% of Rockwood IV lesions showed SLAP lesions. A
      complete supraspinatus tear was detected in 1 case, and partial articular-sided
      supraspinatus tears were detected in 2 cases. Four patients sustained an
      accompanying fracture. CONCLUSION: Concomitant injuries to the shoulder girdle
      obtained during traumatic AC joint separation may be more frequent than
      previously thought. Clinical diagnosis may be difficult in the setting of an
      acute and painful dislocated AC joint. Shoulder arthroscopy during arthroscopic
      AC joint stabilization may aid in detecting associated injuries.

PMID- 18725653
TI  - Hamstring graft size prediction: a prospective clinical evaluation.
AB  - BACKGROUND: Recently we retrospectively collected clinical data to predict
      hamstring graft diameter. Prospective data collection will improve and further
      define prediction of hamstring graft size. HYPOTHESIS: Clinical anthropometric
      data can be used to predict hamstring graft size. STUDY DESIGN: Cohort study
      (prevalence); Level of evidence, 1. METHODS: Fifty consecutive patients with
      anterior cruciate ligament deficiency scheduled for reconstruction using
      hamstring autograft were prospectively evaluated. Preoperatively we recorded
      height, weight, body mass index, age, gender, leg length, thigh length, shank
      length, bilateral thigh circumference, and Tegner score. Intraoperative
      measurements of both the gracilis and semitendinosus tendons were made, including
      absolute length before fashioning the graft and final diameter of the quadrupled
      graft using sizing tubes calibrated to 0.5 mm. Bivariate correlation coefficients
      (Pearson r) were calculated to identify relationships among clinical data and
      intraoperatively measured hamstring graft length and diameter. RESULTS: Strongest
      correlations for graft lengths were height and leg length measurements. Shorter
      persons with shorter leg, thigh, and shank lengths tended to have shorter
      gracilis and semitendinosus grafts. Likewise, the strongest correlations for
      graft diameter were weight and thigh circumference. Self-reported activity level
      and age did not correlate. Gender comparison revealed that women who were
      shorter, lighter, and had smaller body mass indices were more likely to have
      smaller graft diameters and shorter graft lengths. CONCLUSION: Patients weighing
      less than 50 kg, less than 140 cm in height, with less than 37 cm thigh
      circumference, and with body mass index less than 18 should be considered at high
      risk for having a quadrupled hamstring graft diameter less than 7 mm. When
      separated by gender, small graft diameters are most likely in older, short,
      female subjects with small thigh circumferences or young, skinny, male subjects
      with small thigh circumferences and low body mass index. Common clinical
      measurements can be used for preoperative identification of patients at risk for
      insufficient graft tissue and would be useful for patient counseling and
      alternative graft source planning.

PMID- 18725654
TI  - Repair of large chondral defects of the knee with autologous chondrocyte
      implantation in patients 45 years or older.
AB  - BACKGROUND: Autologous chondrocyte implantation (ACI) has become an accepted
      option for the treatment of chondral defects in carefully selected patients.
      Current recommendations limit this procedure to younger patients, as insufficient
      data are available to conclusively evaluate outcomes in patients older than 45
      years. HYPOTHESIS: Cartilage repair with ACI in patients older than 45 years
      results in substantially different outcomes than those previously reported for
      younger age groups. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      This prospective cohort study reviewed patients > or =45 years of age at the time
      of treatment with ACI. The clinical evaluation included a patient satisfaction
      questionnaire and four validated rating scales: Short Form-36, Modified
      Cincinnati Rating Scale, WOMAC (Western Ontario and McMaster Universities)
      Osteoarthritis Index, and the Knee Society Score. RESULTS: A total of 56 patients
      > or =45 years of age were treated with ACI. The average patient age at index
      surgery was 48.6 years (range, 45-60 years). The minimum follow-up was 2 years
      (range, 2-11 years; mean, 4.7 years). The cohort included 36 men and 20 women.
      The mean transplant size was 4.7 cm(2) per defect (range, 1-15.0 cm(2)) and 9.8
      cm(2) per knee (range, 2.5-31.6 cm(2)). Twenty-eight patients (50%) underwent
      concomitant osteotomies to address malalignment. There were 8 failures (14%): 6
      of 15 (40%) in patients receiving workers' compensation (WC) and 2 of 41 (4.9%)
      in non-WC patients. Additional arthroscopic surgical procedures were required in
      24 patients (43%) for periosteal-related problems and adhesions; 88% of these
      patients experienced lasting improvement. At their latest available follow-up,
      72% of patients rated themselves as good or excellent, 78% felt improved, and 81%
      would again choose ACI as a treatment option. CONCLUSION: Our results showed a
      failure rate of ACI in older patients that is comparable with rates reported in
      younger patient groups. The procedure is associated with a substantial rate of
      reoperations, mostly for the arthroscopic treatment of graft hypertrophy, similar
      to that in younger patients.

PMID- 18725655
TI  - Distinct response time distributions in attention deficit hyperactivity disorder
      subtypes.
AB  - OBJECTIVE: To address the issue of response time (RT) profiles in hyperactive
      impulsive (ADHD-HI), inattentive (ADHD-IA), and combined (ADHD-C) subtypes of
      ADHD. We hypothesized that children with ADHD-HI should respond more rapidly than
      children without ADHD and children with ADHD-IA and ADHD-C should respond more
      slowly than children without ADHD. METHOD: Four groups (3 ADHD groups and 1 non
      ADHD group) each composed of 16 children (7-13 years old) performed a
      visuospatial choice task. RESULTS: ANOVA indicated very variable RTs for each
      ADHD subtype when controlling for individual RT. ANOVA performed on RT
      distribution showed significant differences between the ADHD and non-ADHD groups:
      biased to fast responses in ADHD-HI and biased to slow responses in ADHD-IA and
      ADHD-C. CONCLUSION: The results suggest that response time profiles were abnormal
      in all ADHD subtypes and were markedly different between children meeting
      criteria for ADHD-HI and those meeting criteria for ADHD-IA or ADHD-C.

PMID- 18725656
TI  - Children with attention deficits concentrate better after walk in the park.
AB  - OBJECTIVE: In the general population, attention is reliably enhanced after
      exposure to certain physical environments, particularly natural environments.
      This study examined the impacts of environments on attention in children with
      ADHD. METHOD: In this within subjects design, each participant experienced each
      of three treatments (environments) in single blind controlled trials. Seventeen
      children 7 to 12 years old professionally diagnosed with ADHD experienced each of
      three environments-a city park and two other well-kept urban settings-via
      individually guided 20-minute walks. Environments were experienced 1 week apart,
      with randomized assignment to treatment order. After each walk, concentration was
      measured using Digit Span Backwards. RESULTS: Children with ADHD concentrated
      better after the walk in the park than after the downtown walk (p = .0229) or the
      neighborhood walk (p = .0072). Effect sizes were substantial (Cohen's d =.52 and
      .77, respectively) and comparable to those reported for recent formulations of
      methylphenidate. CONCLUSION: Twenty minutes in a park setting was sufficient to
      elevate attention performance relative to the same amount of time in other
      settings. These findings indicate that environments can enhance attention not
      only in the general population but also in ADHD populations. "Doses of nature"
      might serve as a safe, inexpensive, widely accessible new tool in the tool kit
      for managing ADHD symptoms.

PMID- 18725657
TI  - Two new rating scales for assessment of ADHD symptoms in italian preschool
      children: a comparison between parent and teacher ratings.
AB  - OBJECTIVE: Two new rating scales are presented for the assessment of ADHD
      symptoms in Italian preschool children, and the agreement between parents and
      teachers on the presence of an ADHD profile is examined. METHOD: The scales were
      administered to parents and teachers of 180 children with a mean age of 5 years
      and 9 months, attending final year of the Italian preschool system
      (kindergarten). RESULTS: Despite the good psychometric properties of the scales,
      parent and teacher agreement was poor and parents endorsed more symptomatic
      behaviors in their children than the teachers, especially for the hyperactive
      dimension, although they did not necessarily associate these with the presence of
      a potential problem. CONCLUSIONS: The low correspondence between teachers and
      parents shows that ADHD rating scales, although useful screening instruments, are
      not sufficient for diagnosis and must be combined with other tools.

PMID- 18725659
TI  - Editorial: East meets West. Whither our orthopaedic journals?

PMID- 18725658
TI  - An altered pattern of circulating apolipoprotein E3 isoforms is implicated in
      preeclampsia.
AB  - Preeclampsia is a common pregnancy complication that is an important cause of
      preterm birth and fetal growth restriction. Because there is no diagnostic test
      yet available for preeclampsia, we used a proteomic approach to identify novel
      serum/plasma biomarkers for this condition. We conducted case control studies
      comparing nulliparous women who developed preeclampsia at 36-38 weeks of
      gestation with healthy nulliparous women matched by gestational age at sampling.
      Serum/plasma was depleted of six abundant proteins and analyzed by two
      dimensional gel electrophoresis (n = 12 per group) and difference gel
      electrophoresis (n = 12 per group). Differences in abundance of protein spots
      were detected by univariate and multivariate statistical analyses. Proteins were
      identified by mass spectrometry and expression of selected proteins was validated
      by immunoblotting. Proteins whose concentrations were selectively associated with
      preeclampsia included apolipoprotein E (apoE), apoC-II, complement factor C3c,
      fibrinogen, transthyretin, and complement factor H-related protein 2. An increase
      in a deglycosylated isoform of apoE3 and concomitantly decreased amounts of one
      apoE3 glycoisoform were identified in preeclamptic plasma and confirmed by
      immunoblotting. Altered production of these preeclampsia-related apoE3 isoforms
      might impair reverse cholesterol transport, contributing to arterial damage.
      These findings point to a novel mechanistic link between preeclampsia and
      subsequent cardiovascular disease.

PMID- 18725660
TI  - Understanding of informed consent and surgeon liability by the public and
      patients.
AB  - PURPOSE: To evaluate understanding of the fundamental concepts of informed
      consent by the public and patients. METHODS: Questionnaires were distributed to
      any persons (aged more than 16 years) attending the Palmerston North Hospital
      (excluding in-patients). The first 1000 completed questionnaires were analysed
      using the Chi squared test. RESULTS: The fundamental concepts of informed consent
      were not appreciated by most respondents; only 18%, 13%, and 5% of them agreed
      with its implications in terms of self-autonomy, confidentiality, and battery,
      respectively. 64% of respondents preferred to take sole responsibility to decide
      which procedure to undergo, 31% preferred to be guided by the surgeon, and 5% by
      a brief explanation only. 21% of the respondents considered the surgeon liable in
      the event of an unmentioned rare complication, 43% considered the surgeon not
      liable, and 34% were undecided. CONCLUSION: Understanding of medico-legal
      implications of informed consent (e.g. self-autonomy, confidentiality, and
      battery) by the public and patients is poor. Their expectations regarding self
      autonomy seem unrealistic. It is time for surgeons, legal experts, and the public
      to confer and make informed consent a practical, user-friendly tool rather than
      the legal obstacle that it is today.

PMID- 18725661
TI  - Proximal femoral nail failures in extracapsular fractures of the hip.
AB  - PURPOSE: To review patients with proximal femoral nails (PFNs) in our hospital
      that developed complications and needed revision. METHODS: Between January 2000
      and June 2006, records of 216 patients with PFN fixations for traumatic
      extracapsular trochanteric fractures (n=160), pathological fractures (n=23), and
      as a prophylactic measure for metastasis (n=33) were retrospectively reviewed.
      The injury mechanism, reduction technique and quality, and time to and cause of
      implant failure were recorded. RESULTS: 12 PFNs failed: 8 in the trauma group, 3
      in the pathological group, and one in the prophylactic nailing group. Two PFNs
      broke at the proximal lag screw level at a later stage secondary to non-union of
      the pathological fractures. One broke at the level of the distal locking screw at
      an early stage, as the locking holes were too close to the fracture. CONCLUSION:
      Poorly reduced fractures tend to fail early, whereas late failures are due to non
      union. Good reduction with minimal dissection, the use of appropriate nail
      length, and proper positioning of the nail and screws are necessary to avoid
      failure or revision.

PMID- 18725662
TI  - Mini-incision dynamic condylar screw fixation for comminuted subtrochanteric hip
      fractures.
AB  - PURPOSE: To review the results of indirect reduction and mini-incision dynamic
      condylar screw (DCS) fixation for comminuted subtrochanteric femoral fractures.
      METHODS: 29 men and 14 women aged 25 to 65 (mean, 44) years with comminuted
      subtrochanteric femoral fractures underwent indirect reduction and mini-incision
      DCS fixation. Fractures were classified according to the AO classification (10
      type 32B and 33 type 32C) and Seinsheimer classification (6 type III, 15 type IV,
      and 22 type V). Functional outcomes were assessed using the Harris hip score and
      Merle d'Aubigne score. RESULTS: The mean time to full weight bearing was 11
      (range, 8-19) weeks. The mean time to union was 16 (range, 13-22) weeks. There
      were no cases of non-union or implant failure after a mean follow-up period of 25
      (range, 18-30) months. Seven patients had a mean limb length discrepancy of 1.5
      (range, 1-2) cm. Two patients had coxa vara and persistent limp. According to the
      Harris hip score, functional results were excellent in 12 and good in 31
      patients. The mean Harris hip score was 88 (range, 80-99) and the mean Merle
      d'Aubigne score was 17 (range, 14-18). There was no deep infection or avascular
      necrosis of the femoral head. Restriction of knee flexion beyond 90 degrees was
      noted in 2 patients. CONCLUSION: Results of indirect reduction and mini-incision
      DCS fixation for comminuted subtrochanteric femoral fractures are favourable.
      Proper planning and execution of the technique is required to achieve good
      functional outcomes and avoid complications. Preservation of vascularity of the
      medial fragments leads to rapid callus formation and early union and hence avoids
      implant failure and secondary bone grafting.

PMID- 18725663
TI  - Conventional muscle-reflection approach versus mini-incision muscle-splitting
      approach in dynamic hip screw fixation.
AB  - PURPOSE: To compare the short-term results of conventional versus mini-incision
      approaches to dynamic hip screw (DHS) fixation. METHODS: 41 geriatric patients
      with either basal femoral neck or intertrochanteric fractures (Kyle types I to
      III) who underwent closed reduction and DHS fixation by a single surgeon were
      retrospectively reviewed. From January 2001 to June 2005, 6 men and 19 women aged
      60 to 94 (median, 83) years underwent DHS fixation through a conventional muscle
      reflection approach with a skin incision of 10 cm or more. From July 2005 to
      March 2006, 9 men and 7 women aged 67 to 95 (median, 81) years underwent DHS
      fixation through a mini-incision (4 cm) approach at the lower border of the
      lesser trochanter. Operating time, drain output and duration of drain placement,
      decrease in haemoglobin level and receipt of blood transfusions, deterioration in
      ambulation status, analgesic intake, duration of hospital stay, and bone healing
      time for the 2 groups were compared. An independent observer retrospectively
      assessed the fracture pattern, reduction quality, and bone healing time. RESULTS:
      Compared to patients in the conventional group, those in the mini-incision group
      had shorter operating times (50 vs 43 minutes, p=0.02), a higher proportion whose
      drain was removed within 24 hours (28% vs 69%, p=0.01), and consumed fewer
      dosages of oral analgesics within 48 hours (8 vs 5, p=0.001). Classification of
      the fracture pattern in 21 of 38 patients were consistent between the surgeon and
      observer. The Kappa value for agreement was 0.32, denoting marginal agreement
      (p=0.003). Reduction quality (p=0.66) and bone healing time (p=0.73) assessed by
      the observer were not significantly different between the 2 groups. CONCLUSION:
      The short-term clinical outcome of mini-incision DHS fixation for geriatric
      pertrochanteric fractures was favourable.

PMID- 18725664
TI  - Twin hook fixation for proximal femoral fractures.
AB  - PURPOSE: To report results of twin hook fixation for proximal femoral fractures
      in comparison to those fixed with the conventional lag screw. METHODS: Between
      August 2005 and July 2006, 2 men and 15 women aged 74 to 94 (mean, 85) years with
      proximal femoral fractures underwent open reduction and internal fixation using
      the twin hook system. The tip-apex distance was compared with that in 20 patients
      treated with the sliding hip screw between August 2004 and July 2005. RESULTS: In
      the 17 patients, the hook was inserted into the centre of the femoral head. Bone
      union was achieved and no intra- or post-operative cut-out or device failure was
      encountered. In patients using the twin hook and sliding hip screw respectively,
      the mean tip-apex distance was 22.3 mm and 14.6 mm (p<0.001). CONCLUSION: Using
      the twin hook system requires more surgical skill than using the sliding hip
      screw, because failure to insert the pin into the centre of the femoral head
      risks intra-articular perforation by the hooks.

PMID- 18725665
TI  - Open intramedullary Kirschner wire versus screw and plate fixation for unstable
      forearm fractures in children.
AB  - PURPOSE: To compare the outcomes of intramedullary Kirschner wire versus screw
      and plate fixation for unstable forearm fractures in children aged older than 10
      years. METHODS: Records of 32 children aged 10 to 15 (mean, 12) years with
      displaced fractures of the radius and ulna were retrospectively reviewed. 17 boys
      and 4 girls underwent intramedullary Kirschner wiring, whereas 10 boys and one
      girl underwent plating. All patients had been initially treated with closed
      reduction and casting. Indications for surgical intervention were fractures with
      angulation of >10 degrees and total displacement. Patients were followed up for a
      mean of 24 (range, 13-40) months. Angulation and range of movements of the elbow,
      wrist, and forearm, as well as clinical and cosmetic results were compared.
      RESULTS: Both treatments achieved excellent clinical outcomes, but intramedullary
      Kirschner wiring resulted in better cosmesis, shorter operating times, easier
      hardware removal, and lower implant costs. CONCLUSION: Intramedullary Kirschner
      wiring is a better option than plating for the treatment of unstable forearm
      fractures in older children.

PMID- 18725666
TI  - "S" Quattro external fixation for complex intra-articular thumb fractures.
AB  - PURPOSE: To report outcomes in 10 patients who underwent dynamic "S" Quattro
      external fixation for complex fractures of the base of the thumb. METHODS: Nine
      men and one woman aged 18 to 69 (mean, 31) years underwent "S" Quattro external
      fixation for complex fractures of the base of the thumb. The dominant hand was
      involved in 8 patients. Three patients had Bennett fractures, 5 had Rolando
      fractures, one had an open multi-fragmented fracture, and one had a fracture
      subluxation. Four of them had had prior (failed) treatment with splints and/or
      Kirschner wires. The "S" Quattro external fixator was applied for a mean of 4.9
      weeks. Patients were followed up in an out-patient setting for a mean of 10.7
      months until bone union and removal of the external fixator. Finger flexor
      function was assessed based on total active movement (TAM). Functional outcomes
      were assessed using the Disability of Arm, Shoulder and Hand (DASH)
      questionnaire. RESULTS: No pin-site infection, malunion, or non-union was
      encountered. Mean loss of TAM was 7.5 degrees. Five patients lost 10 degrees or
      more, 2 of whom lost 20 degrees (one with an open comminuted fracture and one was
      elderly). Four patients regained full TAM and 6 attained more than 75% TAM
      compared to the contralateral thumb. At the 3-year follow-up, the mean DASH score
      was 3.4. Four patients reported no functional disability. Poorer outcomes were
      reported in the 2 patients who once had lost 20 degrees of TAM. CONCLUSION: The
      "S" Quattro external fixator is recommended as a primary and definitive treatment
      modality for complex intra-articular thumb fractures when conservative and other
      surgical interventions have failed.

PMID- 18725667
TI  - The use of qualitative cultures for detecting infection in open tibial fractures.
AB  - PURPOSE: To determine the role of qualitative cultures for detecting infection in
      open tibial fractures. METHODS: From January 2003 to December 2004, 95 men and 13
      women (mean age, 34 years) with open tibial fractures in one or both limbs and
      without any other sites of infection were prospectively studied. Patients who had
      been treated with intravenous or oral antibiotics before presentation and/or had
      undergone debridement or other surgery were excluded. RESULTS: Infection was not
      correlated with age, sex, interval from injury to debridement, and cause of
      fracture. The association of infection with predebridement cultures was stronger
      (odds ratio=12.5) than that with postdebridement cultures (odds ratio=4.7).
      CONCLUSION: Pre- and post-debridement cultures have a role in detecting infection
      in open tibial fractures. For detecting infection, predebridement cultures have
      better sensitivity, while postdebridement cultures have better specificity.

PMID- 18725668
TI  - Computed tomography-guided radiofrequency ablation of osteoid osteomas.
AB  - PURPOSE: To report on 14 patients with osteoid osteomas treated by computed
      tomography-guided radiofrequency ablation. METHODS: Nine males and 5 females aged
      13 to 45 (mean, 25) years with osteoid osteomas were included. The proximal tibia
      was the commonest site involved. A bipolar 18-gauge radiofrequency probe with a 9
      mm active tip was used. A 4.5-mm hollow drill was introduced into the nidus.
      Energy application was started at 2 W and increased to a maximum of 5 W. Heat was
      applied for 4 to 6 minutes at 90 degrees Celsius. RESULTS: 12 (86%) of the 14
      patients had prompt pain relief; the remaining 2 underwent a repeat ablation.
      After a mean follow-up period of 19 (range, 9-25) months, no patient had pain
      recurrence. CONCLUSION: Radiofrequency ablation is a minimally invasive and cost
      effective treatment for osteoid osteomas.

PMID- 18725669
TI  - Tumour volume and lung metastasis in patients with osteosarcoma.
AB  - PURPOSE: To assess the association between tumour volume and occurrence of lung
      metastasis in patients with osteosarcoma and to determine the cut-off value.
      METHODS: Records of 70 patients with histopathologically confirmed primary
      osteosarcoma in the extremities who had magnetic resonance imaging and computed
      tomography of the thorax less than one month before treatment were reviewed, with
      reference to the official report of tumour dimensions and lung metastasis by
      radiologists. The status of lung metastasis was assessed. Tumour volume was
      measured using the formula for an ellipsoidal mass. RESULTS: Of the 70 patients
      with osteosarcoma, 33 (47%) had evidence of lung metastasis. Tumour volume was
      directly associated with occurrence of lung metastasis (p=0.048). The proportion
      having lung metastasis when the primary tumour volume exceeded 371 cm3 was 69%,
      compared to 34% in those with smaller tumours. CONCLUSION: Larger tumours are
      more likely to correlate with lung metastasis. Both features are predictive of
      patient survival and prognosis.

PMID- 18725670
TI  - Effect of the Deyo score on outcomes and costs in shoulder arthroplasty patients.
AB  - PURPOSE: To evaluate the effect of preoperative comorbidity status (defined by
      the Deyo index) on hospital mortality, postoperative complications, length of
      hospital stay, and hospital costs for shoulder arthroplasty patients. METHODS:
      The overall mean hospital mortality and postoperative complication rates, and
      length of hospital stay and hospital costs stratified by the Deyo score were
      compared using the Pearson Chi squared test and the F-test, respectively. The
      effects of the Deyo score on hospital mortality and postoperative complications
      were estimated using multiple logistic regression. The length of hospital stay
      and hospital costs were estimated using multiple linear regression. The magnitude
      of the estimated effects of the Deyo score on the 4 outcomes were expressed as
      crude odds ratios (ORs) and adjusted ORs for age, race, gender, surgeon volume,
      and hospital volume. RESULTS: Higher Deyo scores tended to be associated with
      higher hospital mortality, length of hospital stay, postoperative complications,
      and hospital costs. Compared with the referent group (Deyo score=0), patients
      with the highest Deyo scores (5-36) exhibited adjusted ORs of 11.8 for hospital
      mortality (p=0.011) and 1.1 for developing postoperative complications (p=0.098),
      and had the highest length of hospital stay (mean, 4.1 days) and hospital costs
      (mean, US$18,549). CONCLUSION: The Deyo score was a predictor of outcomes and
      costs in the shoulder arthroplasty population. By identifying relevant factors,
      health care providers can better determine who should be referred for shoulder
      arthroplasty and what should be considered when assessing risks and benefits.

PMID- 18725671
TI  - Comparison of functional and radiological outcomes after computer-assisted versus
      conventional total knee arthroplasty: a matched-control retrospective study.
AB  - PURPOSE: To compare the radiological and functional outcomes of patients who
      underwent either computer-assisted or conventional total knee arthroplasty (TKA).
      METHODS: Two groups of 50 patients each underwent either computer-assisted or
      conventional TKA were retrospectively studied. Patients were matched according to
      body mass index (BMI), gender, and age. Three senior orthopaedic surgeons with
      comparable experience performed all surgeries, using 3 different prostheses. The
      surgical approach and peri- and postoperative regimens were the same. The
      mechanical axis and the tibial and femoral angles were measured using
      standardised long-leg weight-bearing radiographs. Overall function was assessed
      using the Short Form-12 (SF-12) and International Knee Society (IKS) scores.
      RESULTS: No intra-operative technical difficulties were encountered in either
      group. The computer-assisted group resulted in more consistent and accurate
      alignments in both the coronal and sagittal planes and better SF-12 and IKS
      scores. In obese patients (BMI=30 kg/m2 or more), computer-assisted TKA provided
      better alignment than the conventional technique. CONCLUSION: Computer-assisted
      TKA improves implant positioning, limb alignment, and overall functional outcome.
      It may be particularly advantageous for obese patients.

PMID- 18725672
TI  - Midterm outcome of the Duracon total knee arthroplasty.
AB  - PURPOSE: To present midterm results of Duracon total knee arthroplasty (TKA)
      performed between 1991 and 2001. METHODS: One man and 43 women (65 knees) aged 46
      to 84 (mean, 63) years who underwent primary TKAs using the Duracon prosthesis
      performed by a single surgeon were followed up for a mean of 8.5 (range, 5-11)
      years. All TKAs were cruciate-retaining and cemented, with only 9 of the patellae
      resurfaced. The diagnosis was osteoarthritis in 42 patients (61 knees), and
      rheumatoid arthritis in 2 patients (4 knees). Patients were assessed using the
      Knee Society Clinical Rating System, the Oxford Knee Score, and the Knee Society
      Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. RESULTS:
      The mean Knee Society knee score was 86 (range, 43-100) and the function score
      was 68 (0- 100). 94% of patients reported no or only mild pain. The mean Oxford
      Knee Score was 19. There was no patellofemoral complication, deep vein thrombosis
      or pulmonary embolism. Complications included a superficial infection and an
      uncontrolled deep infection. One patient had the insert exchanged for wear at the
      11-year follow-up, and another had the polyethylene insert and tibial tray
      revised after a motorcycle accident. CONCLUSION: The Duracon TKA had good midterm
      clinical results with absence of patellofemoral complications.

PMID- 18725673
TI  - Harris-Galante II acetabular cup: a survival analysis.
AB  - PURPOSE: To determine the survival rate of the Harris-Galante (HG) II cup and
      identify factors contributing to failure. METHODS: 271 primary total hip
      arthroplasties (THAs) performed between 1992 and 1999 in our hospitals using the
      HG II acetabular cup were retrospectively reviewed due to a high incidence of
      liner dissociation. RESULTS: 48 THAs were revised, 32 (67%) of which were due to
      liner dissociation. The Kaplan-Meier 10-year survival rate was 73%. Dislocation
      (p<0.001) and acetabular size (p=0.042) were independent predictors of acetabular
      component failure in the Cox's regression model. CONCLUSION: The long-term
      outcome of the HG II cup is unsatisfactory. Although the HG II cup is no longer
      produced, numerous patients have this prosthesis in situ and should be reviewed
      regularly, as liner dissociation and retroacetabular osteolysis may occur.

PMID- 18725674
TI  - Cone femoral prosthesis for osteoarthritis of the hip with femoral dysplasia.
AB  - PURPOSE: To assess the clinical and radiological outcomes of total hip
      replacement (THR) using the cone femoral prosthesis. METHODS: Four men and 15
      women (26 hips) aged 19 to 78 (mean, 45) years underwent THR for osteoarthritis
      of the hip with femoral dysplasia using the cone femoral prosthesis. Only 17
      patients (24 hips) were available for review. Pain and functional limitation were
      assessed using the Oxford hip score. Stable fixation by bone ingrowth was defined
      as no subsidence or radiolucent lines around the prosthesis. RESULTS: The mean
      follow-up duration was 50 (range, 25-92) months. The mean Oxford hip score
      improved from 44 (range, 32-54) preoperatively to 17 (range, 12-28) at the latest
      follow-up. Prosthesis survival was 100%. All prostheses showed stable integration
      with bony ingrowth and no measurable subsidence. 15 hips had excessive
      anteversion of 25 to 90 degrees. No patient had venous thromboembolism, deep
      prosthetic infections or dislocations. CONCLUSION: The cone prosthesis is less
      complex and expensive than the modular prosthesis. The early functional and
      radiological outcomes were excellent, with marked improvement in pain and
      function. This constitutes effective treatment for osteoarthritis of the hip with
      femoral dysplasia.

PMID- 18725675
TI  - Laminoplasty for patients aged 75 years or older with cervical myelopathy.
AB  - PURPOSE: To assess the neurological and walking status of 56 elderly patients
      after cervical myelopathy to determine whether the surgery was justified.
      METHODS: Records of 23 men and 33 women aged 75 to 86 (mean, 79) years who
      underwent laminoplasty for cervical myelopathy were retrospectively reviewed.
      They had been followed up for a mean of 3.5 (range, 0.2-8.6) years. Walking
      status was assessed according to long-term care insurance criteria. In 45
      patients with more than 2 years of follow-up, neurological status was evaluated
      according to the Japanese Orthopaedic Association (JOA) score. Neurological
      recovery rate was classified as excellent, good, fair, poor, and worse. RESULTS:
      Postoperatively, of the 47 patients still living, 22 could walk independently, 22
      required assistance outdoors, 2 were using a wheelchair, and one was bedridden.
      The mean JOA score was 9.7 preoperatively, 12.2 one year postoperatively, and
      11.8 at final assessment (p<0.001). The mean neurological recovery rate was 29%
      at one-year follow-up and 24% at final assessment (p=0.06). CONCLUSION: Although
      excellent results were not expected in elderly patients, surgery to maintain
      independent walking status was justified in most of our patients.

PMID- 18725676
TI  - V osteotomy and Ilizarov technique for residual idiopathic or neurogenic
      clubfeet.
AB  - PURPOSE: To report the treatment outcomes of V osteotomy and Ilizarov technique
      for residual idiopathic or neurogenic clubfeet. METHODS: 13 patients (14 feet)
      aged 8 to 18 years underwent V osteotomy via the calcaneus and talus, followed by
      gradual distraction of soft tissue and bone for foot reconstruction. Eight of the
      clubfeet were idiopathic and had undergone previous surgeries. The remaining 6
      were neurogenic and their pathologies were: Charcot-Marie-Tooth disease (n=2),
      myelomeningocele (n=2), neurofibromatosis (n=1), and distal arthrogryposis (n=1).
      Three of them had undergone previous surgeries. The Ilizarov frames were retained
      for 3 to 6 months and the patients were followed up for 1.8 to 8.9 years. Range
      of movement of the ankle and foot, appearance and position, gait, pain, function,
      and patient satisfaction were assessed according to the modified clubfoot grading
      system. The talo-1st metatarsal angle was measured on anteroposterior
      radiographs. RESULTS: Scores associated with the appearance and position of the
      foot, and thus patient satisfaction were significantly improved, but not for
      range of movement, pain, and function. The mean preoperative and final talo-1st
      metatarsal angles were 39.7 and 8.7 degrees, respectively (p<0.01). Ten feet
      achieved the plantigrade position, one had residual equinus, and 3 had residual
      adduction and supination. CONCLUSION: Patient satisfaction improved significantly
      despite no major improvement in pain, function, and range of movement of the
      ankle and foot. This reflects the importance of the appearance and position of
      the foot, and justifies the decision to undergo this long and demanding
      procedure.

PMID- 18725677
TI  - Autologous versus pooled human serum for articular chondrocyte growth.
AB  - PURPOSE: To evaluate the effect of autologous human serum (AHS) versus pooled
      human serum (PHS) versus foetal bovine serum (FBS) for growth of articular
      chondrocytes and formation of chondrocytefibrin constructs. METHODS: Experiments
      with monolayer culture expansion of human articular chondrocytes were performed
      using basic culture media supplemented with 10% AHS, PHS, or FBS. Growth kinetics
      and specific phenotypic expression of the serially expanded chondrocytes were
      evaluated. Large-scale culture expansion was used to obtain about 30 million
      cells to form chondrocyte-fibrin constructs. All constructs were implanted
      subcutaneously at the dorsum part of athymic nude mice for 8 weeks. The in vivo
      constructs were evaluated using histological and gene expression studies.
      RESULTS: The morphology of primary cultured chondrocytes (P0) was polygonal and
      became more elongated and larger after serial passages (P1, P2, and P3). This was
      comparable for AHS, PHS, and FBS. Total cell yields accumulated for AHS (28
      million) and PHS (41 million) were significantly higher than those for FBS (4
      million). After 8 weeks of implantation, in vivo chondrocyte-fibrin constructs
      demonstrated a glistening white and firm texture, comparable to normal hyaline
      cartilage. All constructs exhibited histo-architectural characteristics of well
      distributed cartilage-isolated cells embedded within basophilic ground substance.
      Presence of accumulated proteoglycans cartilage-rich matrix was indicated by
      positive orange-red Safranin O staining. During monolayer culture expansion,
      collagen type II gene expression was down-regulated, while collagen type I gene
      expression was up-regulated. Collagen type II--the specific chondrogenesis marker
      -was re-expressed in the in vivo chondrocyte-fibrin construct. CONCLUSION: AHS
      and PHS are better than FBS for in vitro cultivation of human articular
      chondrocytes.

PMID- 18725678
TI  - Autologous chondrocyte transplantation in the repair of full-thickness focal
      cartilage damage in rabbits.
AB  - PURPOSE: To compare the efficacy of autologous chondrocyte transplantation (ACT)
      versus non-operative measures for cartilage repair in rabbits. METHODS: Nine New
      Zealand white rabbits were used. Identical focal defects were created in the
      articular cartilage of both knees. One month later, the right knee was repaired
      via ACT, while the left knee was left untreated (control group). The quality of
      cartilage tissues in both knees was compared 3 months later, according to the
      quantitative analysis of glycosaminoglycan (GAG) in the cartilage and macroscopic
      examination of histology using the Brittberg/International Cartilage Research
      Society (ICRS) score. RESULTS: Microscopic examination showed enhanced
      regeneration following ACT repair. Quantification analysis revealed significantly
      higher cellular expression of GAG in the ACT-treated knees (1.12 vs 0.81
      microgram GAGs/mg protein, p=0.008). The mean Brittberg/ICRS score was
      significantly higher in the treated knees (6.00 vs 1.89, p=0.007). CONCLUSION:
      ACT is superior to non-operative measures for repairing focal cartilage defects,
      as determined by favourable histological and immunohistological outcomes at the
      cellular level.

PMID- 18725679
TI  - The use of hydroxyapatite blocks for innominate osteotomy: a report of three
      cases.
AB  - We evaluated the use of hydroxyapatite blocks as spacers in pelvic osteotomy. The
      hydroxyapatite blocks fused with autologous bone tissue within 10 months and were
      highly biocompatible even after 10 years. They prevent pelvic deformities and are
      as effective as autogenous bone grafts.

PMID- 18725680
TI  - Acute plastic bowing of the forearm in adults: a report of two cases.
AB  - We report 2 adult cases where the diagnosis of acute plastic bowing of the
      forearm was either delayed or missed. In a 21-year-old man, ulnar bowing was
      missed and fixation was not performed because the patient had no limitation to
      his range of movement or pain. In a 24-year-old woman, the presentation of bowing
      in both the ulna and radius was delayed and corrective osteotomy was necessary
      for restoration of full range of movement. Prompt diagnosis enables manual
      reposition for easy restoration of full range of movement.

PMID- 18725681
TI  - Axillary artery injury secondary to displaced proximal humeral fractures: a
      report of two cases.
AB  - We report 2 cases of axillary artery injury secondary to low-energy proximal
      humeral fractures. In case 1, early diagnosis based on signs of acute ischaemia
      of the arm enabled early treatment and a favourable outcome. In case 2, there
      were no signs of ischaemia or neurological deficit, resulting in delayed
      diagnosis and increased severity of the injury. The patient developed a false
      aneurysm and sepsis and eventually died. A high index of suspicion is necessary
      for diagnosing an axillary artery injury. We recommend that all patients with
      proximal humeral fractures with severe medial displacement of the shaft and a
      bone spike should routinely undergo Doppler ultrasound scanning to rule out
      vascular injuries and the presence of a false aneurysm.

PMID- 18725682
TI  - Brachial artery aneurysm rupture in a patient with neurofibromatosis: a case
      report.
AB  - Peripheral vascular manifestations of neurofibromatosis are rare but may result
      in fatal haemorrhaging when they rupture. Surgeons should be aware of this life
      threatening condition. We report a case of 35-year-old woman with
      neurofibromatosis who presented with a swollen and tender mass around her right
      arm. Angiography revealed 2 aneurysms in the brachial artery. Surgical occlusion
      revealed a large amount of clotted blood within the subfascial space, and the
      bleeding point was identified as a pinpoint opening in the aneurysm. The brachial
      artery abutting the aneurysm and the surrounding soft tissues was extremely
      brittle and fragile, with massive oozing during dissection. The brachial artery
      was irreparable and was resected after ligation of the artery and surrounding
      soft tissues and the aneurysm. Despite an uneventful recovery, the patient died
      on day 4.

PMID- 18725683
TI  - Verrucous carcinoma of the foot: a case report.
AB  - We present a case of verrucous carcinoma of the foot in a 34-year-old man. This
      is a rare, locally invasive, well-differentiated, low-grade squamous cell
      carcinoma, with human papilloma virus as a possible causative agent. It follows a
      chronic course and mimics a variety of skin lesions, delaying diagnosis by up to
      15 years. The definitive diagnosis is made histologically, and treatment by wide
      local excision is recommended. Our patient underwent wide local excision and
      partial 5th metatarsal amputation because of invasive disease, local infection,
      and peripheral vascular disease. There were no postoperative complications. At
      the 10-year follow-up, there were no signs of tumour recurrence.

PMID- 18725684
TI  - Ilizarov technique for correction of the Shepherd's crook deformity: a report of
      two cases.
AB  - We report 2 patients with fibrous dysplasia who underwent correction, using the
      Ilizarov technique, of Shepherd's crook deformities and pathological fractures of
      the left femurs. A 12-year-old boy underwent an opening wedge osteotomy and a 48
      degree gradual correction, whereas a 43-year-old woman underwent a 34-degree
      acute correction without osteotomy at the fracture site. Both patients could
      initiate early weight bearing. Final leg function was excellent and alignment was
      maintained. No complications were encountered. Both patients had no difficulty
      sleeping and no major complaints about the Ilizarov technique. It is more
      important to achieve accurate alignment than resection of the lesion. The
      Ilizarov technique is effective for treating the Shepherd's crook deformity in
      patients with fibrous dysplasia.

PMID- 18725685
TI  - Osteosynthesis for a T-shaped fracture of the femoral neck and trochanter: a case
      report.
AB  - Ipsilateral fractures of the femoral neck and trochanter are uncommon. We report
      a 30-year-old man with a T-shaped fracture separating the trochanter and neck
      from the head. He underwent osteosynthesis using a dynamic compression plate,
      screws, and pins. Bone union occurred 4 months postoperatively. At the one-year
      follow-up, the patient was free of pain and had no evidence of avascular
      necrosis. It is important to preserve the femoral head in young patients by
      preventing further compromise of the tenuous blood supply.

PMID- 18725686
TI  - Osteoid osteoma of the talus: a case report.
AB  - Diagnosing osteoid osteomas in the small bones of the hands and feet is difficult
      because of their atypical presentations. We report an 8-year-old boy who
      presented with pain in the left ankle and a limp. Plain radiographs of the ankle
      and foot were normal; the diagnosis was eventually made using magnetic resonance
      imaging.

PMID- 18725687
TI  - Histiocytic osteolysis secondary to hyperbilirubinaemia: a case report.
AB  - A 6-year-old boy with Alagille syndrome, characterised by marked
      hyperbilirubinaemia, presented with malunion of a pathological fracture of the
      femur with local bone atrophy and insufficient callus formation. During
      corrective osteotomy, it was noted that the femur was stained dark green,
      suggestive of bilirubin deposition. Histology of the resected bone revealed the
      presence of many histiocytes and osteoclast-like multinucleate giant cells
      containing bilirubin particles in the cytoplasm causing bone resorption. These
      findings suggest that bilirubin may activate macrophages to form osteoclast-like
      multinucleate giant cells, resulting in histiocytic osteolysis.

PMID- 18725688
TI  - Surgical wound mucormycosis necessitating hand amputation: a case report.
AB  - We report an unusual case of cutaneous mucormycosis in a 17-year-old man who had
      no risk factors for fungal infection. The aggressive nature of cutaneous
      mucormycosis is illustrated. A high index of suspicion is crucial for identifying
      and preventing progression of this disease, which can lead to limb amputation,
      even death. Extra vigilance should be given to those who are immunocompromised,
      including those receiving short courses of steroids. Early recognition, prompt
      surgical intervention and initiation of an appropriate antifungal treatment are
      crucial in the management of this rare but potentially limb- and life-threatening
      infection.

PMID- 18725689
TI  - Dextrose prolotherapy for recalcitrant coccygodynia fractures.

PMID- 18725691
TI  - Prediction of peak forces for a shortening smooth muscle tissue subjected to
      vibration.
AB  - The objective of the present study is to investigate the peak forces for a
      tracheal smooth muscle tissue subjected to an applied longitudinal vibration
      following isotonic shortening. A non-linear finite element analysis was carried
      out to simulate the vibratory response under experimental conditions that
      corresponds to forced length oscillations at 33 Hz for 1 second. The stiffness
      change and hysteresis estimated from the experimental data was used in the
      analysis. The finite element results of peak forces are compared to the
      experimental data obtained. The comparison of results indicate that the approach
      and the vibratory response obtained may be useful for describing the cross-bridge
      de-attachments within the cells as well as connective tissue connections
      characteristic of tracheal smooth muscle tissue.

PMID- 18725692
TI  - Comparison of cellular proliferation on dense and porous PCL scaffolds.
AB  - In this contribution, PCL (poly-epsilon caprolactone) scaffolds were prepared by
      solvent-casting/particle-leaching technique in the presence of two pore formers,
      PEG(4000) or sucrose molecules in different quantities (0, 10, 20, 30, 40, 50, 55
      w/w% PEG(4000)/PCL; 10, 20 w/w% Sucrose/PCL). The surface and bulk properties of
      the resulting scaffolds were studied by SEM, DSC and FTIR. SEM photographs showed
      that, macroporosity was obtained in the PCL structures prepared with sucrose
      crystals while microporous structure was obtained in the presence of PEG(4000)
      molecules. Average pore diameters calculated from SEM photographs were 40.1 and
      191.2 mum for 40% PEG(4000)/PCL and 10% Sucrose/PCL scaffolds, respectively. The
      DSC and FTIR results confirmed that there is no any interaction between pore
      formers and PCL during structural formation, and both pore formers, PEG(4000) and
      sucrose, remained independently in the scaffolds. L929 mouse fibroblast cells
      were seeded onto PCL structures and maintained during 7 days to evaluate cell
      proliferation. Cell culture results showed that, 10% Sucrose/PCL scaffold was the
      most promising substrate for L929 cell growth due to 3-D architecture and
      macroporous structure of the scaffold.

PMID- 18725693
TI  - Culture medium study of human mesenchymal stem cells for practical use of tissue
      engineering and regenerative medicine.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells that have potential to
      differentiate into various phenotypes and appear useful for therapeutic
      applications in regenerative medicine. Mesenchymal Stem Cell Basal Medium (MSCBM;
      Cambrex) is a widespread and suitable medium used in MSC cultivation, but it is
      extremely difficult to use generally for clinical treatment because of its
      unclear traceability and cost. Assessment of cost-effectiveness is a critical
      issue for successful practical application; therefore, we have evaluated the
      effects of a generally used medium, Dulbecco's Modified Eagle's Medium (D-MEM) on
      the expansion of MSCs in comparison with MSCBM. To isolate human MSCs, bone
      marrow aspirates were taken and cultured in MSCBM or D-MEM. Proliferation assay
      indicated that MSCs isolated in both media showed a similar growth rate. When
      supplemented with osteo-inductive reagents, alkaline phosphatase activity was not
      significantly different between cells in D-MEM and MSCBM. Moreover, the cells
      expressed identical mesenchymal lineage markers, but not endothelial and
      hematopoietic lineage markers. Our findings suggest that cells obtained from bone
      marrow and cultured in D-MEM might possess proliferative capacity and the
      potential to differentiate into an osteogenic lineage. In conclusion, D-MEM might
      be a suitable basal medium for the cultivation of MSCs for clinical applications.

PMID- 18725694
TI  - Electron beam irradiated UHMWPE: degrading action of air and hyaluronic acid.
AB  - Ultra high molecular weight polyethylene, both pure and electron beam irradiated,
      was exposed to air and hyaluronic acid. Physical and mechanical analyses were
      performed in order to check the polymeric change due to the treatment. Pure
      UHMWPE, in fact, was modified by the hyaluronic acid that plasticizes the
      polymer. The electron irradiation cross links the chains and prevents their
      sliding in acid presence. A low irradiation dose is preferable rather than an
      high one. Low doses induce low amount of free radicals, witch react with oxygen
      and hyaluronic acid inducing low polymer degrade maintaining the initial
      mechanical performance. High doses degrade significantly the polymer
      properties.100 kGy irradiation in air can be applicable on the polyethylene as
      well as a compromise between the low mechanical performance improving and the
      material degradation.

PMID- 18725695
TI  - Mechanical characterization of ultra-high molecular weight polyethylene
      hydroxyapatite nanocomposites.
AB  - An experimental study of Ultra-High Molecular Weight Polyethylene (UHMWPE) and
      hydroxyapatite (HAP) nanocomposites for the purpose of joint prosthesis is
      investigated under quasi-static and dynamic loading conditions. By employing
      compression mold process, five different volume fractions of hydroxyapatite
      nanoparticle reinforced nanocomposites are made. Quasi-static tension and
      compression tests are performed using ASTM test methods. Dynamic compression
      characterization is performed using split Hopkinson pressure bar technique. The
      nanocomposite performance as a function of volume fraction under a typical
      loading rate is investigated. The results of the fabricated nanocomposites are
      compared with currently employed UHMWPE in the joint implants. For comparison
      purposes, separate sets of tests are performed on currently employed UHMWPE. This
      comparison provides a valid measure to identify the optimum volume fraction of
      hydroxyapatite that can be used without compromising the integrity of the UHMPWPE
      in joint prosthesis.

PMID- 18725697
TI  - A longitudinal study of the relationship between empowerment and burnout among
      registered and assistant nurses.
AB  - The relation between empowerment and burnout was investigated using a two-wave
      and two-variable panel model. A questionnaire was completed on two occasions, one
      year apart, by 1,356 nurses. The paths in the model were estimated using
      regression analyses and the following results were obtained: (a) empowerment is a
      stable state; (b) higher levels of empowerment are related to lower levels of
      burnout, when empowerment and burnout are studied at the same point in time; (c)
      higher prior levels of empowerment can be associated with higher later levels of
      burnout, when empowerment and burnout are studied at different points in time;
      (d) for assistant nurses, but not for registered nurses, prior higher levels of
      burnout resulted in lower later levels of empowerment, indicating a reciprocal
      relation between the two concepts. The results imply that what is a protective
      factor from a cross-sectional perspective may be a risk factor from a
      longitudinal perspective.

PMID- 18725696
TI  - Low density lipoprotein adsorption on sol-gel derived alumina for blood
      purification therapy.
AB  - Among the clinical treatments of Familial Hyper cholesterolemia patients to
      reduce the concentration of low density lipoprotein (LDL), blood purification
      therapy is most suitable in which a blood-compatible adsorbent is employed. In
      the present study, alumina powders were prepared via a sol-gel route to develop a
      LDL-adsorbent Aluminum tri2-propoxide was hydrolyzed and subsequently calcined up
      to 1200 degrees C. Surface charge density and pore size distribution were
      measured, and the phases were identified. The alumina calcined above 400 degrees
      C had excellent blood compatibility in terms of endogenous clotting parameters,
      i.e., partial thromboplastin time: (PTT), prothrombin time: (PT), and the amount
      of fibrinogen: (Fib). The amount of LDL-adsorption (DeltaW(LDL)) increased with
      the calcining temperature, showing a good linear correlation to surface charge
      density. The 1200 degrees C sample consisted only of alpha-alumina, and was
      greatest in DeltaW(LDL). All samples involved pores smaller than 20 nm but not
      the pores large enough to accommodate LDL molecules (20-25 nm). From those
      results, it was concluded for the present alumina particles that the surface
      charge density was the primary factor and that the chemical activity of alpha
      alumina also contributed to the excellent LDL-adsorption for the 1200 degrees C
      sample, while entrapping LDL in the pores was not an active mechanism.

PMID- 18725698
TI  - Prevalence of job strain among Indian foundry shop floor workers.
AB  - Global competition in manufacturing sector demand higher productivity levels. In
      this context, workers in this sector are set with high output targets, leading to
      job strain. In addition to the strain, hazardous conditions also prevail in some
      of the manufacturing processes like foundry activities. This paper attempts to
      appraise the prevalence of job strain among foundry shop floor workers in India
      with the help of Demands-Control model [8]. In this study, data was collected
      through a survey using 49-item Job Content Questionnaire (JCQ) [9], a widely used
      and well-validated test for job strain. Then the data was subjected to
      statistical analysis after ascertaining the reliability. This survey has revealed
      that 25% of workers in foundry were experiencing high job strain. Hazardous
      working conditions, limited decision making authority, etc. appear to be the main
      contributing factors for the higher levels of strain.

PMID- 18725699
TI  - Carrying loads and postural sway in standing: the effect of load placement and
      magnitude.
AB  - This study investigated the effect that load magnitude, load location, and the
      dimensions that the base of support have on postural sway in standing while
      wearing a backpack, single strapped bag, briefcase, or purse. Subjects were
      instructed to carry a load of 10% or 20% of their body weight with either their
      feet spaced shoulder width apart or together for a period of 45 seconds.
      Medial/lateral and anterior/posterior center of pressure (COP) displacement and
      COP velocity were calculated. Overall, it was found that an increase in load
      magnitude produced an increase in postural sway and velocity of COP. In addition,
      a large increase in the medial/lateral COP velocity was observed when subjects
      carried a briefcase, single strapped bag, or purse. Additionally, a larger COP
      sway was recorded in conditions of standing with decreased base of support (feet
      together). These findings suggest the importance of considering the way we carry
      loads in order not only to place less strain on the body and to minimize our
      efforts, but to optimize postural control as well.

PMID- 18725700
TI  - The presence of musculoskeletal disorders among amateur bowlers.
AB  - BACKGROUND: With increasing numbers of adults taking part in amateur athletic
      activity during leisure hours there have been indications that amateur athletic
      activity may have negative effects on musculoskeletal disease. A literature
      review focusing on musculoskeletal injuries among bowlers provided only limited
      references. STUDY OBJECTIVES: Studying the characteristic of bowlers complaining
      of musculoskeletal disorders in general and of upper extremity cumulative trauma
      disorders specifically, and locating the factors that statistically predict
      musculoskeletal disorders among Israeli bowlers. METHODS: The research population
      includes 98 amateur bowlers who attended two bowling clubs (cluster sampling).
      Musculoskeletal disorders of the research population were assessed by subjective
      report using the Standardized Nordic Questionnaires. Further use was made of
      questionnaires concerning bio-demographic data, work assessment, and the
      characteristics of the bowling game. RESULTS: Sixty two percent of bowlers
      reported the presence of musculoskeletal symptoms in one or more of their body
      joints during the preceding year. Regression analysis with the number of painful
      joints in the upper extremities as a dependent variable revealed one main
      predictor: the number of leagues in which the bowler participated (beta = 0.22, p
      < 0.03). When the dependent variable was the number of painful joints in the
      entire body, the statistical predictor was the average achievement of the bowlers
      (beta = 0.40, p < 0.001). CONCLUSIONS: Research findings shed light on the unique
      musculoskeletal disorders of bowlers. Bowlers should be instructed with regard to
      what are the safe limits of their leisure activities.

PMID- 18725701
TI  - Conceptual framework of sickness absence and return to work, focusing on both the
      individual and the contextual level.
AB  - AIM: The aim of this study is to give an overview of the individual and workplace
      level factors affecting sickness absence and return to work based on
      international literature. Categorizing the individual and workplace level factors
      in a conceptual framework encompasses both sickness absence and return to work.
      Testing the practical use of the conceptual framework "The Dynamic Work
      Disability Model" in study design and interpretation of five studies in a Danish
      context. METHODS: The project features five prospective cohort studies focusing
      on associations between work environment and different sickness absence and
      return to work outcomes. These five studies utilize two different work
      environment cohorts and a national sickness absence register data. The following
      analyses were performed: Logistic, Cox, multilevel logistic and Poisson
      regressions. RESULTS: A research project on sickness absence and return to work
      designed according to the "The Dynamic work Disability Model" contributed to an
      understanding of the proportions and basic epidemiology of work disability in a
      Danish labor market context. The use of "The Dynamic Work Disability Model"
      helped in designing and structuring the research project's sub-studies and
      supported a more systematic interpretation of the findings.

PMID- 18725702
TI  - Effects of government policies on the work of home care personnel and their
      occupational health and safety.
AB  - The health sector in Quebec (Canada) is dealing with profound macro-economic and
      macro-organizational changes. This article is interested in the impact of these
      changes on the work of home health aides (HHAs) and home care nurses and their
      occupational health and safety (OHS). The study was carried out in the home care
      services (HCS) of four local community service centres (CLSC) with different
      organizational characteristics. It is based on an analysis by triangulation of 66
      individual and group interviews, 22 observed workdays and 35 observed
      multidisciplinary or professional meetings, as well as on administrative
      documents. HHAs are experiencing an erosion of their job because the relational
      and affective aspects of their work are disappearing. This may be due to an
      increase in their physical workload, leading to an increase in musculoskeletal
      problems and, to a lesser extent, in psychological health problems. Nurses are
      seeing an increase in the volume of invisible work that they have to do, which
      also has the effect of decreasing the relational aspects of their activity. The
      increasingly numerous psychological health problems are the consequence of this
      change in their profession. This study also shows that managers' decisions at the
      local level can reduce or increase the work constraints of HHAs and nurses.
      Examples of good practices for HHAs are the stabilization of clienteles and the
      possibility of organizing their itinerary, while for nurses, it is in how
      clientele follow-up tools are implemented. This article discusses the effects of
      government policies and decisions on the work and OHS of home care personnel. To
      address this subject, we use a specific analysis of the workload of home health
      aides (HHAs) and nurses. We will show the relationships between managers'
      organizational choices to respond to governmental constraints and the resulting
      work changes. We will also look at their consequences on occupational health and
      safety (OHS) and on the work of different personnel.

PMID- 18725703
TI  - Development of a carpal tunnel syndrome screening method using structured
      interviews and vibrotactile testing.
AB  - Carpal tunnel syndrome (CTS) is a debilitating and expensive health problem. An
      inexpensive screening method that would differentiate between people who do not
      have CTS and those that may have CTS would be useful. The screening methodology
      investigated here had two phases: a structured interview and provocative
      vibrotactile testing (VT). The control group (n = 36) was composed of
      asymptomatic college students and faculty, the case group was composed of
      patients currently visiting an occupational medicine clinic for symptoms
      consistent with CTS. The case group was subdivided into positive and negative for
      nerve conduction latency, NCL+ (n = 21) and NCL- (n = 13), respectively. Using a
      scored, structured interview, 33 of the controls and none of the symptomatic
      cases were identified as non-CTS. The results from the provocative flexion VT
      indicated that if the difference between the age corrected baseline and the
      threshold at 15 minutes is 15 microm or more, the subject was likely to be NCL+
      (odds ratio 12.6, 95% CI 3.8 to 41.8). Further research may improve this
      screening methodology to not only determine whether or not a person has CTS, but
      also to determine the level of median nerve impingement or damage.

PMID- 18725704
TI  - Multi-professional vocational rehabilitation group meetings with female clients:
      a qualitative study.
AB  - Many women require vocational rehabilitation before they can return to work. The
      objective with the present study was to describe female clients' situation during
      the rehabilitation process, as it became apparent during the rehabilitation
      meetings with the various actors involved. The clients' diagnoses varied, but the
      majority was affected with musculoskeletal disorders. The meetings were audio
      taped and transcribed verbatim, after which they were analysed by qualitative
      content analysis. The following themes emerged: Adaptation to the rehabilitation
      group; client's health status; the workplace's significance for rehabilitation;
      and the client's decision-point. Conflict between health and work was immensely
      important for rehabilitation. Differences in attitude were apparent during the
      rehabilitation meetings, as some clients were passive and exercised less
      influence on the planning, than the other more active clients did.

PMID- 18725705
TI  - Physical training of combat diving candidates: implications for the prevention of
      musculoskeletal injuries.
AB  - Physical training (PT) is a significant component in the operational preparation
      for Canadian Forces (CF) combat divers. However, in developing the various
      components of a PT program, consideration must be given to the potential for
      increasing the risk of injury. Indeed, all PT programs should incorporate
      components that minimize risks of injury, thereby attempting to prevent injury.
      This report identifies high-risk activities associated with PT during a CF Combat
      Diving Course and contains recommendations for PT modifications. Major high-risk
      activities identified were: inappropriate exercises, errors in exercise
      prescription, particularly in intensity and duration and incorrect lifting
      methods. From a specificity of training perspective, there is little support for
      the incorporation of 'dry land flutter kick' (i.e., repetitive, unsupported
      alternating straight leg raises), or high repetitions of push-ups, sit-ups and
      chin-ups in the training of CF combat diving candidates. Excessive use of these
      exercises, as performed during training, pose a high-risk for injury and are not
      recommended.

PMID- 18725706
TI  - Which work factors determine job satisfaction?
AB  - BACKGROUND: Job satisfaction is associated with mental health. Employees could be
      counselled on how they feel about their work. If specific aspects of their job
      are causing particular dissatisfaction, they could be assisted to appropriately
      change these aspects. OBJECTIVE: There is no 'gold standard' indicating the
      aspects that should be taken into account when job satisfaction is measured. This
      study investigated which work factors determine job satisfaction. METHOD: A self
      report questionnaire was sent to a random sample of 822 out of 1908 active
      employees. The questionnaire examined overall job satisfaction as well as
      satisfaction with specific work aspects using valid single-item measures.
      RESULTS: The response rate was 63%. Overall job satisfaction was 5.3 +/- 1.3 on a
      Likert-scale ranging from 1 (strongly disagree) to 7 (strongly agree). The work
      factors explained 54% of the variance in job satisfaction. Specific satisfaction
      with task variety, colleagues, working conditions, and workload were positively
      related to overall job satisfaction, as were career perspectives and job
      autonomy. CONCLUSION: Task variety, working conditions, workload, and career
      perspectives determine the greater part of job satisfaction. An instrument
      including these factors would provide beneficial information beyond current
      measures of job satisfaction.

PMID- 18725707
TI  - Content validity and utility of the Assessment of Work Performance (AWP).
AB  - In the area of work rehabilitation, many decisions about future interventions for
      the client are based on the results of various kinds of assessments. Therefore,
      it is important that the assessment instruments used are adequate, useful, and
      reliable. The purpose of this study was to investigate the content validity and
      utility of the instrument Assessment of Work Performance (AWP) which is used to
      assess an individual's observable (working) skills during work performance, i.e.
      how efficient and appropriate a client performs a work activity. A questionnaire
      was answered by 67 respondents who used the AWP in various work rehabilitation
      settings in Sweden. The result indicates content validity and utility for the AWP
      that supports further testing of the instrument.

PMID- 18725708
TI  - Organizational impact on psychosocial working conditions.
AB  - Using a multilevel approach, this study explores how job demands and control are
      dependent on the organizational context in which work is performed. The data set
      consisted of 3,485 employees at 51 establishments divided into 141 sub-units and
      belonging to 10 parent organizations. Data were collected by means of a survey
      answered by the employees and structured interviews conducted with operative
      managers at participating establishments. The results showed that a significant
      proportion of the variance in job demands and control was attributed to the
      organization, and that the three organizational levels varied in terms of their
      impact on the two psychosocial dimensions. More specifically, job demands were
      mostly affected by the establishment level, while the sub-unit level seemed to be
      the most important for job control. It is concluded that in studies of working
      conditions, the organizational context should be considered.

PMID- 18725709
TI  - Self-rated quality of life among the young unemployed and the young in work in
      northern Sweden.
AB  - This study analysed self-assessed quality of life (QoL), using a QoL
      questionnaire (Hornquist's QLcs) covering life spheres, somatic health, mental
      well-being, cognitive ability, social and family life, activity, financial
      situation, meaning in life and a global score "entire life", for young people
      aged 18-24 in a population-based cross-sectional study in northern Sweden. Of
      these, 651 were unemployed and 2802 were in work (employed, students and in
      military service). Results showed that the young unemployed exhibited poorer QoL
      than the young in work and the greatest difference was found regarding their
      financial situation. Young men rated somatic health and mental well-being higher
      than young women. However, QoL in other essential domains was rated higher by
      young women in work. Close friends and money reserve were important for all
      participants, no matter whether they were employed or not. The risk of being
      young and unemployed was greater if the person had a worse financial situation,
      shorter education, and fewer leisure activities with other people. Finally, it
      was concluded that while QoL is poorer when in unemployment - both for the young
      and those who are older (aged 25-64) - psychological well-being, in contrast to
      several previous studies, is even poorer for young people than for those who are
      older. This is worrying in a public health perspective and could have
      implications for unemployment policies for younger and less well-educated age
      groups.

PMID- 18725710
TI  - Workplace health interventions in small enterprises: a Swedish longitudinal
      study.
AB  - This article has a two-fold approach. First, it investigates relationships
      between work organizational factors, and health and performance outcomes. Second,
      it compares two change strategy approaches in workplace health interventions by
      studying changes of these factors and outcomes. The sample consisted of ten
      Swedish small enterprises including 102 individuals, who answered a before and
      after questionnaire about organizational factors and outcomes. The leaders were
      interviewed and answered a questionnaire about performed workplace health
      interventions. Statistical methods used were reliability tests, correlation
      analyses and t-tests. Results indicate rather strong links between indicators of
      respectful leadership, creative work and team spirit, and the outcome indicators
      self-assessed health and judged workplace adaptability in association with
      customer satisfaction. The results concerning changes of determinants and
      outcomes (after workplace health interventions) showed significant differences
      between enterprises using a broad change strategy and those using an
      expert/problem-based strategy with the former having more favourable results. The
      leader interview results also point at obstacles concerning workplace change
      processes as lack of resources, insufficient competence and influence of external
      factors. The study results suggest that work organizational factors and
      integrated models for workplace health intervention are of importance for health
      and performance outcomes in small enterprises.

PMID- 18725711
TI  - Disadvantagement-related correlates of career optimism among college and
      university students with disabilities.
AB  - This paper describes research regarding factors predicting career optimism for a
      group of postsecondary students with disabilities (N = 208) who were enrolled in
      seven colleges and universities in four states. Career optimism was defined as a
      student's self-confidence regarding his or her ability to choose, maintain, and
      advance in an appropriate career. The proposed model incorporated variables
      related to employment discrimination and disincentives such as perceived impact
      of disability on one's education and quality of life, racial/ethnic status,
      gender, and presence of disability benefits. Results indicated that two aspects
      of "disadvantagement," specifically severity of perceived impact of disability
      and racial/ethnic status, were significant predictors of career optimism.
      Implications of the findings were discussed in terms of informational
      interventions, curricula, development of self-advocacy and self-determination,
      and research topics.

PMID- 18725712
TI  - Supermarket workers: their work and their health, particularly their self
      reported musculoskeletal problems and compensable injuries.
AB  - A literature review revealed that cashiers are the most studied of all
      supermarket workers, while little is known about other types of employees.
      However, cashiers are far from being the only supermarket workers affected by
      musculoskeletal disorders. The musculoskeletal health of supermarket employees
      other than cashiers was therefore examined for one company. Two sources of data
      were used: compensation statistics (from the company's 57 corporate supermarkets)
      and self-reported questionnaires (administered in 4 selected stores). These
      sources provided very different descriptive statistics, both in terms of the size
      of problems (depending on which aspects were compared, compensation statistics
      depicted 2 to 18 times fewer disorders than self-reports), and in terms of which
      body regions were most affected. There were also discrepancies with regard to
      identifying those departments which were most at risk (wrappers according to self
      reports, delicatessen according to compensation reports). According to self
      reports, 83% of workers (excluding cashiers) reported at least one
      musculoskeletal disorder over a 12-month period, and 32% had problems severe
      enough to impede regular activities. Different approaches to calculating rates
      were also used within each data source. Calculations using the number of hours
      worked annually by all workers were deemed to be the best. The significance of
      these results for supermarket employees and in terms of intervention and
      prevention in other sectors is examined.

PMID- 18725713
TI  - Extent and sources of occupational stress in university staff.
AB  - Canadian higher education sector has undergone numerous changes during the past
      decades. Increased student enrolments, massive cuts in human resources and
      constant restructuring are changes likely to have had a considerable impact on
      all employees (e.g., administrative, trades, and faculty). While many studies
      conducted in different countries have shown that stress in universities is a
      problem of alarming proportions, to date, no study of the entire staff of a
      university has been carried out in Canada. This research uses an approach based
      on the prevention and management of the sources of occupational stress to study
      1086 employees of a Quebec university. Data were collected by means of
      questionnaires and semi-structured interviews. It was found that the proportion
      of individuals who reported a high level of psychological distress was twice as
      high (40%) than that reported for a Quebec-wide sample (20%). Work overload, the
      relationship with one's superior and participation in decision making were
      systematically reported as high risks to employees' health. It was found that
      human resources management practices have not followed the rapid organizational
      changes which affected the university in the past years. The results are
      discussed in light of the risk management approach.

PMID- 18725714
TI  - Simultaneous bio-reduction of trichloroethene, trichloroethane, and chloroform
      using a hydrogen-based membrane biofilm reactor.
AB  - The contamination of water by chlorinated solvents is recognized as a serious and
      widespread problem throughout the industrialized world. Here, we focus on three
      chlorinated solvents that are among those most commonly detected and that have
      distinct chemical features: trichloroethene (TCE), trichloroethane (TCA), and
      chloroform (CF). Because many contaminated waters contain mixtures of the
      chlorinated solvents, a treatment technology that detoxifies all of them
      simultaneously is highly desirable. The membrane biofilm reactor (MBfR) is a
      recent technological advance that makes it possible to deliver H(2) gas to
      bacteria efficiently and safely, despite hydrogen's low water solubility and risk
      of forming a combustible atmosphere when mixed with air. The objectives of this
      work are to document whether or not the three chlorinated compounds can be
      dechlorinated simultaneously in a H(2)-based MBfR and to determine if competitive
      or inhibitory interactions affect bio-reduction of any of the solvents. The main
      finding is a demonstration that directly using H(2) as the electron donor makes
      it possible to bio-reduce combinations of different chlorinated solvents. This
      finding supports that the H(2)-based MBfR can treat multiple chlorinated solvents
      in one step, addressing a common groundwater situation. We saw possible evidence
      of inhibition by CF at a concentration greater than about 1 muM, competition for
      H(2) from sulfate and nitrate reductions, and possible inhibition of TCE
      reduction from the accumulation of chloroethane (CA) or chloromethane (CM).

PMID- 18725715
TI  - Trophic structure of stream macroinvertebrate communities revealed by stable
      isotope analysis.
AB  - The trophic structure of a macroinvertebrate community was investigated using
      carbon and nitrogen stable isotopes analysis (delta(13)C and delta(15)N) at three
      longitudinal sites along the main channel of the Hirose River, Japan, and at an
      outlet site of the tributary reservoir. Along the main channel, primal food
      supply gradually changed from allochthonous to autochthonous source. The
      percentage of autochthonous origin of the macroinvertebrate community calculated
      by a carbon-mixing model (=38-83%) increased with that of suspended fine
      particulate organic matter (FPOM = 21-67%), a main resource for filtering
      collectors that dominated the communities. The lowest percentage of autochthonous
      in the lake outlet community (=21%) was a result of the notably low percentage
      autochthonous of FPOM due to the decomposition of allochthonous coarse
      particulate organic matter (e.g., leaf) strained in the reservoir. Predators had
      higher mean delta(15)N than non-predators in three sites. The average enrichments
      of delta(15)N signature per trophic level for all sites were 3.82 per thousand
      from producers to first consumers and 1.24 per thousand from first to second
      consumers. Our data suggest the strong potential for stable isotope analysis to
      enhance our understanding of the trophic structure of stream macroinvertebrate
      community.

PMID- 18725716
TI  - Comparative survival of enteric indicators, E. coli and somatic and F-RNA
      bacteriophages on turf-grass irrigated with recycled water.
AB  - The aim of this study was to elucidate whether the current withholding period of
      4 hours following irrigation of public recreational areas with some classes of
      recycled water, as prescribed in some Australian state regulations, is valid or
      whether the holding time can be reduced under specified ambient conditions. A
      secondary objective was to evaluate laboratory simulations of ambient field
      conditions for microbial survival experiments. Results suggest that the currently
      prescribed 4 hour withholding period achieves a reduction of health risk
      associated with bacterial enteric pathogens that would not otherwise occur if the
      withholding period was reduced. However, this may not be the case for viral
      enteric pathogens as the survival of bacteriophages, PRD-1 and MS-2 on turf-grass
      did not significantly change even after 6 hours, except PRD-1 under high solar
      conditions. These results suggest that bacteriophages, PRD-1 and MS-2 are more
      conservative indicators of enteric pathogen survival on UV exposed turf-grass
      compared with E. coli. The simulations of field conditions in the laboratory were
      somewhat problematic, with the variations in natural conditions that occur
      temporally, sometimes for short periods, difficult to reproduce.

PMID- 18725717
TI  - Zero Liquid Discharge approach in plating industry: treatment of degreasing
      effluents by electrocoagulation and anodic oxidation.
AB  - Degreasing waste effluents issued from a surface treatment plant were treated by
      electrochemical techniques in an attempt to reduce COD so that clean water can be
      returned to the rinse bath. Electrocoagulation, both with iron and aluminium
      anodes, and anodic oxidation with boron doped diamond (BDD) anodes were tested.
      In the electrocoagulation tests, the nature of the anodes did not impact
      significantly the reduction of COD. Electrocoagulation showed good COD removal
      rates, superior to 80%, but it was not able to reduce COD down to low levels.
      Anodic oxidation was able to reduce COD down to discharge limits; the oxidation
      efficiency was superior to 50%. Economical calculations show that anodic
      oxidation is best used as a polishing step after electrocoagulation. The bulk of
      the COD would be reduced by electrocoagulation and, then, anodic oxidation would
      reduce COD below discharge limits. The maximum treatable flow is somewhat
      hindered by the small sizes of current BDD installation but it would reach 600
      m(3)/year if anodic oxidation is coupled with electrocoagulation, the operational
      cost being 2.90 Euros /m(3).

PMID- 18725718
TI  - The use of microcalorimetry to compare the biological activity of a CAS and a MBR
      sludge-application to pharmaceutical active compounds.
AB  - Micropollutants removal, such as pharmaceutical substances, during wastewater
      treatment processes is becoming a greater issue everyday. In order to optimize
      it, their biodegradation processes have to be better understood. So far,
      microcalorimetry has been used worldwide to investigate chemical reactions. For
      few years now it has also been developed to model and control biological
      processes. In the case of micropollutants, respirometry is, most of the time, not
      precise enough to determine biodegradation. That is why, microcalorimetric
      experiments have been set up. For this purpose, a 2 L Bio-RC1 (Mettler-Toledo)
      has been modified to reach a resolution of 5-10 mW.L(-1).In this study, the
      biodegradation rate of standard substrates (Ethanol and Ammonia) by an activated
      sludge from a full-scale CAS and one from a MBR pilot plant operating in parallel
      have been compared by means of microcalorimetry. Then few trials to determine the
      biodegradation of selected pharmaceutical substances, as well as the eventual
      inhibition induced by them have been made. The first results did not exhibit any
      biological activity. However, they have displayed inhibition for both studied
      substances.

PMID- 18725719
TI  - Comparative efficacy of five different rep-PCR methods to discriminate
      Escherichia coli populations in aquatic environments.
AB  - Development of efficient techniques to discriminate the sources of E. coli in
      aquatic environments is essential to improve the surveillance of fecal pollution
      indicators, to develop strategies to identify the sources of fecal contamination,
      and to implement appropriate management practices to minimize gastrointestinal
      disease transmission. In this study the robustness of five different rep-PCR
      methods, such as REP-PCR, ERIC-PCR, ERIC2-PCR, BOX-PCR and (GTG)(5)-PCR were
      evaluated to discriminate 271 E. coli strains isolated from two watersheds
      (Lakelse Lake and Okanagan Lake) located in British Columbia, Canada. Cluster
      analysis of (GTG)(5)-PCR, BOX-PCR, REP-PCR, ERIC-PCR and ERIC2-PCR profiles of
      271 E. coli revealed 43 clusters, 35 clusters, 28 clusters, 23 clusters and 14
      clusters, respectively. The discriminant analysis of rep-PCR genomic fingerprints
      of 271 E. coli isolates yielded an average rate of correct classification
      (watershed-specific) of 86.8%, 82.3%, 78.4%, 72.6% and 55.8% for (GTG)(5)-PCR,
      BOX-PCR, REP-PCR, ERIC-PCR and ERIC2-PCR, respectively. Based on the results of
      cluster analysis and discriminant function analysis, (GTG)(5)-PCR was found to be
      the most robust molecular tool for differentiation of E. coli populations in
      aquatic environments.

PMID- 18725720
TI  - Optimization of the indole photodegradation on supported TiO(2): influences of
      temperature, concentration, TiO(2) amount and flow rate.
AB  - This work describes the photodegradation of aqueous indole solutions by using
      TiO(2) supported on cellulose fibres. Four parameters were studied: the indole
      concentration; the TiO(2) amount; the temperature and the flow rate. Central
      composite experimental design was used to determine the influences of the
      parameters on the indole degradation percentage. We demonstrate that in our
      experimental domain the quasi complete degradation of indole is in all cases
      reached and more interestingly that it is possible to find unique values of
      TiO(2) amount and flow rate leading to optimised photodegradation of indole in
      the studied domains of temperature and indole concentration.

PMID- 18725721
TI  - Effects of different hydraulic models on predicting longitudinal profiles of
      reactive pollutants in activated sludge reactors.
AB  - This paper presents effects of dispersion on predicting longitudinal ammonia
      concentration profiles in activated sludge bioreactor located at "Wschod" WWTP in
      Gdansk. The aim of this study was to use the one-dimensional advection-dispersion
      Equation (ADE) to simulate the flow conditions (based on the inert tracer
      concentrations in selected points) and longitudinal profile of reactive pollutant
      (based on the ammonia concentration profiles in selected points). The simulation
      results were compared with the predictions obtained using a traditional "tanks-in
      series" (TIS) approach, commonly used in designing biological reactors. The use
      of dispersion coefficient calculated from an empirical formula resulted in
      substantial differences in the tracer concentration distributions in two sampling
      points in the bioreactor. Simulations using the one-dimensional ADE and TIS
      model, with the nitrification rate incorporated as the source term, revealed that
      the hydraulic model plays a minor role compared to the biochemical
      transformations in predicting the longitudinal ammonia concentration profiles.

PMID- 18725722
TI  - A framework for planning of sustainable water and sanitation systems in peri
      urban areas.
AB  - There are billions of people around the world that lack access to safe water
      supply and basic sanitation, a situation which puts the affected in severe health
      conditions as well as economical and social despair. Many of those lacking
      adequate water supply and sanitation systems can be found at the fringe of the
      cities in so called peri-urban areas, especially in the developing world.
      Planning in these areas is highly complex due to challenging environmental and
      physical conditions, high population density and unclear institutional
      boundaries. This article presents a framework aiming to support the planning
      process for sustainable water and sanitation systems in peri-urban areas. The
      suggested framework is based on different available planning approaches from a
      review of literature and websites of organisations and companies. It consists of
      a recommendation of important steps in the planning process as well as supporting
      tools. Further, it incorporates a set of sustainability criteria important for
      the peri-urban context and allows for the development of site specific systems.
      The framework has the aim to be flexible for different planning situations, and
      for suiting planners with different perspectives and amount of resources.

PMID- 18725723
TI  - Amoebae-resisting bacteria in drinking water: risk assessment and management.
AB  - Free-living amoebae have been detected in a large number of man-made water
      systems, including drinking water distribution systems. Some of these amoebae can
      host amoebae-resisting bacteria, and thus act potentially as reservoirs and
      vehicles for a number of pathogens. The objectives of this study were to
      characterize the amoebae and amoebae-resisting bacteria present in different raw
      waters used for drinking water production, and to assess the efficiency of
      different treatments applied for drinking water production in removing or
      inactivating these amoebae. The preliminary results of this study confirm the
      presence of amoebae and amoebae-resisting bacteria in raw waters used for
      drinking water production. Due to their capacity to encyst, most of these amoebae
      are extremely resistant to disinfection processes. In these conditions,
      preventing the dissemination of these micro-organisms through drinking water will
      mainly require their physical removal by clarification and filtration processes.
      The particular hazard that amoebae-resisting bacteria represent in drinking water
      production should be taken into account in any risk assessment conducted in the
      framework of a water safety plan, and control strategies based on physical
      removal rather than disinfection should be adopted where necessary.

PMID- 18725724
TI  - Detection and source identification of faecal pollution in non-sewered catchment
      by means of host-specific molecular markers.
AB  - Multiple host-specific molecular markers were used to detect the sources of
      faecal pollution in a mixed land use non-sewered catchment in Southeast
      Queensland, Australia. These markers included human-specific Bacteroides (HF183
      and HF134), cattle-specific Bacteroides (CF128), dog-specific Bacteroides
      (BacCan) and human-specific enterococci surface protein (esp) markers. The
      sensitivity and specificity of these markers were determined by testing 197
      faecal samples from 13 host groups. The overall sensitivity and specificity of
      these markers was high (sensitivity>/=85% and specificity>/=93%) indicating their
      suitability for detecting the sources of faecal pollution. Of the 16 samples
      collected from the study area, 14 (87%) were positive for at least one of the
      molecular marker tested. Amongst all the markers, cattle-specific CF128 was more
      prevalent than others, followed by human-specific HF183 which was consistently
      detected in samples collected from sites within close proximity to urban
      development. Significant correlations were found between E. coli and enterococci
      concentrations with the positive/negative results of human-specific Bacteroides
      HF183 (p<0.001, p<0.0001) and HF134 (p<0.001, p<0.004) markers. No correlations
      were found between faecal indicators (E. coli or enterococci) with the CF128 or
      BacCan markers. A significant correlation was also found between enterococci
      concentrations and the presence/absence of the esp marker (p<0.02). Based on the
      results, it appears that the host-specific markers such as HF183 and esp are a
      sensitive measure of sources of human faecal pollution in surface waters in
      Southeast Queensland, Australia.

PMID- 18725725
TI  - Identifying common traits among Australian irrigators using cluster analysis.
AB  - In Australia there is a growing awareness that the over-allocation of water
      entitlements to irrigators needs to be reduced so that environmental flow
      allocations can be increased. This means that some water will need to be acquired
      from irrigators and returned to the environment. Most current water reform
      policies assume that irrigators are solely motivated by profit and will be
      willing sellers of water, but this might be an untenable approach. Authorities
      will need to consider new ways of encouraging the participation of irrigators in
      water reform. The main aim of this research was to identify the non-commercial
      influences acting on irrigators' behaviour, especially the influence of the
      values that they hold toward family, land, water, community and lifestyle. The
      study also aimed to investigate whether it is possible to group irrigators
      according to these values and then use the groupings to describe how these might
      affect their willingness to participate in environmental reforms. We clustered
      the irrigators into three groups with differing orientations; (i) Investors [25%]
      profit oriented, (ii) Lifestylers [25%]-lifestyle oriented, (iii) Providers [50%]
      family-succession oriented. This research indicates that when designing policy
      instruments to acquire water for environmental purposes policy-makers should pay
      more attention to the factors influencing irrigators' decision making, especially
      non-commercial factors.

PMID- 18725727
TI  - Treatment of a landfill leachate containing compounds of pharmaceutical origin.
AB  - Paper reports the results of landfill leachate treatment with membrane
      bioreactor, nanofiltration and ozonation. Investigated leachate encompasses a
      number of specific compounds of pharmaceutical origin, including a suite of by
      products deriving from the production of vitamin C and propyphenazone. Low
      biodegradability was observed in MBR (16%) for propyphenazone, while the removal
      of intermediates from the vitamin C-synthesis was moderate, reaching 30% for
      diacetone sorbose (DAS) and 69% for diacetone alpha-keto-gulonic acid (DAG).
      Ozonation almost completely removed propyphenazone but failed to significantly
      oxidise intermediates from the vitamin C-synthesis. Nanofiltration of the
      leachate succeeded to remove 99% of DAG and 79% of propyphenazone which made it
      the most efficient among techniques used.

PMID- 18725728
TI  - Alternative water sources and endotoxin.
AB  - The primary objective of this preliminary study was to ascertain the
      concentration of endotoxin in a variety of Australian water types, including
      recycled water. A total of 42 sampling sites were surveyed, the majority on at
      least 2 separate occasions (total number of samples analysed was 76). Samples
      were collected from a variety of locations throughout Australia including:
      drinking water distribution (12), drinking water reservoir (4), wastewater
      treatment train (11) and finished recycled water (15). Class A recycled waters,
      defined microbiologically in Australian regulations as having <10 E. coli per 100
      mL, where the treatment train did not include membrane filtration, gave rise to
      an average measured endotoxin concentration of 2.030 Endotoxin Units (EU) per mL
      (N=7). For recycled Class A water samples, where membrane filtration was part of
      the treatment train (N=3) the average endotoxin concentration was 41 EU/mL.
      Measured endotoxin concentrations in drinking water varied from <4 to 119 EU/mL.
      Results of this preliminary study indicate that endotoxin concentrations in
      recycled water may be reduced to levels at least as low as those found in
      drinking water but for some recycled waters, where membrane filtration is not
      practiced, higher endotoxin concentrations may persist.

PMID- 18725729
TI  - Modelling of enhanced CSO treatment in secondary clarifiers with a modified
      Activated Sludge Model no. 3.
AB  - An alternative approach for combined water treatment as opposed to its CSO
      discharge into receiving water is its bypass to the inlet of secondary clarifiers
      (SC). To analyse the processes and to evaluate the performance of this approach,
      experiments and numerical modelling were carried out. In batch and pilot scale
      experiments major effects were identified and quantified. The Activated Sludge
      Model No. 3 (ASM3) was modified to simulate the batch and pilot scale experiments
      for implementation of the bypass-specific processes and thus to set up an overall
      balance of the relevant compounds. With some modifications of ASM3, good
      agreement of the modelling results with measurements of COD, nitrogen and
      phosphorus were achieved.

PMID- 18725730
TI  - Electricity production and microbial biofilm characterization in cellulose-fed
      microbial fuel cells.
AB  - Converting biodegradable materials into electricity, microbial fuel cells (MFCs)
      present a promising technology for renewable energy production in specific
      applications. Unlike typical soluble substrates that have been used as electron
      donors in MFC studies, cellulose is unique because it requires a microbial
      consortium that can metabolize both an insoluble electron donor (cellulose) and
      electron acceptor (electrode). In this study, electricity generation and the
      microbial ecology of cellulose-fed MFCs were analyzed using a defined co-culture
      of Clostridium cellulolyticum and Geobacter sulfurreducens. Fluorescent in situ
      hybridization and quantitative PCR showed that when particulate MN301 cellulose
      was used as sole substrate, most Clostridium cells were found adhered to
      cellulose particles in suspension, while most Geobacter cells were attached to
      the electrode. By comparison, both bacteria resided in suspension and biofilm
      samples when soluble carboxymethyl cellulose was used. This distinct function
      related distribution of the bacteria suggests an opportunity to optimize reactor
      operation by settling cellulose and decanting supernatant to extend cellulose
      hydrolysis and improve cellulose-electricity conversion.

PMID- 18725731
TI  - Evaluation of the impact of single-walled carbon nanotubes in an activated sludge
      wastewater reactor.
AB  - This paper evaluated the impact of single-walled carbon nanotubes (SWCNTs) on the
      performance and activated sludge properties in an activated sludge wastewater
      reactor. The reactor was shock loaded with 270 mg/L of 90% purified SWCNTs after
      the reactor reached quasi-steady state and the reactor was monitored for 18 days
      after the shock loading. Various experimental parameters were measured and
      compared. Overall the addition of SWCNTs did not negatively impact the
      performance of the activated sludge reactor; on the other hand, SWCNTs improved
      sludge settleability and sludge dewaterability. The cake solids of the sludge
      were increased and the activated sludge flocs became less negatively charged. The
      positive impacts were more significant in Phase II (after running the reactor for
      one solids retention time, SRT) than that in Phase III (after running for
      additional 1.5 SRT).

PMID- 18725732
TI  - Potential of in-situ sensors with ion-selective electrodes for aeration control
      at wastewater treatment plants.
AB  - A pilot-scale activated sludge wastewater treatment plant (WWTP) operated with
      nitrification and pre-denitrification was monitored with a set of on-line sensors
      for over 3 years. Wet-chemistry ex-situ analyzers, UV and UV-Visible in-situ
      sensors and in-situ sensors based on ion-selective electrodes (ISE) were used.
      New ISE sensors for ammonium, nitrate and nitrite, adapted to water and
      wastewater matrices, have been released in recent years, With adequate quality
      control they proved to be highly accurate and reliable in WWTP influents and
      activated sludge (AS) reactors even at the end of the biological treatment zone,
      working at low ammonium concentrations (1-2 mgN/l). The ammonium measurement was
      used to test several feed-forward and feed-back aeration control strategies. The
      first aim was to keep inorganic nitrogen compounds, i.e. ammonium, nitrate and
      particularly nitrite, as low as possible in the effluent, and within Swiss
      national standards (<2.0 mgNH(4)-N/l, <0.3 mgNO(2)-N/l, 24 h average). All the
      strategies were successful at keeping ammonium low and subsequently at gaining
      denitrification capacity to significantly reduce the total nitrogen discharge.
      Some control strategies however generated temporary peaks of ammonium or even
      accumulation of nitrite.

PMID- 18725733
TI  - Optimisation of aeration for activated sludge treatment with simultaneous
      nitrification denitrification.
AB  - Following a promising study at pilot scale a new aeration control law has been
      implemented at a full scale wastewater treatment plant displaying a conventional
      activated sludge process. The new control law is based on the direct measurements
      of ammonium and nitrate concentration in the biological tank by ion selective
      electrodes. This control law features a cascade of two Predictive Function
      Controls and calculates an optimal air flow rate to be provided to the biomass
      through fine bubble diffusers. The results obtained at the full scale plant
      confirmed the high performance of this control strategy allowing to substantially
      reduce the amount of diffused air while providing an easy means to manage the
      effluent quality to the plant operator.

PMID- 18725734
TI  - 2005 poliovirus eradication: poliovirus presence in Cyprus 2 years after.
AB  - The last case of polio in Cyprus caused by a wild-type poliovirus occurred in
      1995. Since then Cyprus belongs to the countries considered poliovirus-free by
      the WHO. The aim of this study was to confirm the absence of any circulating wild
      type polioviruses and to monitor vaccine-derived polioviruses in Cyprus by
      analysis of sewages. During the course of this study no wild-type polioviruses
      were identified, although the identification of viable oral poliovirus vaccine
      isolates confirmed the presence and circulation of poliovirus vaccine strains in
      sewage in Cyprus.

PMID- 18725735
TI  - Characteristics of bacterial and viral contamination of urban waters: a case
      study in Xi'an, China.
AB  - In order to gain knowledge on the presence of bacteria and viruses in urban
      waters, the authors started a long-term study on the microbiological quality of
      urban lakes and rivers in Xi'an, China. In the current study, enteroviruses were
      chosen as typical viruses and RT-nested PCR was conducted for their detection.
      Universal primers were designed for simultaneous detection of poliovirus,
      coxsackievirus, and enterovirus 71 which are the most frequently encountered
      enteroviruses in China. The RT-nested PCR protocol established in this study
      showed high sensitivity and specificity. The detection limit was equivalent to
      0.038 CCID50 per litre by applying a modified adsorption-elution concentration
      method. No cross-reactivity was observed using the genome of pathogenic bacteria
      as of PCR template. The occurrence of enteroviruses was compared with fecal
      coliform count in a 6-month period from July to December 2006 for the urban
      waters. As a result, it was noticed that the presence of enteroviruses might not
      relate to the fecal coliform count so much. Statistical analysis also indicated
      that there was no significant correlation between the presence of enteroviruses
      and that of total bacteria, total coliform, and fecal coliform.

PMID- 18725736
TI  - Removal of EDTA from low pH printed-circuit board wastewater in a fluidized zero
      valent iron reactor.
AB  - Fluidized zero valent iron (ZVI) process was adopted to reduce
      ethylenediaminetetraacetic acid (EDTA) from low pH printed-circuit board (PCB)
      wastewater for two reasons: (1) low pH of the wastewater favoring the ZVI
      reaction; (2) higher ZVI utilization for fluidized process due to abrasive motion
      of the ZVI. The results showed that the degradation of EDTA was greatly enhanced
      under acidic pH, longer hydraulic detention time (HRT) and presence of dissolved
      oxygen (DO). Without addition of oxygen, 65% of EDTA was removed with capacity of
      7.33 mg EDTA/g ZVI at pH 2, ZVI dosage of 424 g/L and HRT 10 min. With 6.8 mg/L
      of DO, 83% of EDTA was reduced with capacity of 19.01 mg EDTA/g ZVI for the same
      experimental condition. The presence of oxygen/ZVI initiated a Fenton type
      reaction to reduce EDTA. The end product after EDTA degradation was analyzed by
      high performance liquid chromoagraphy (HPLC), where propionic acid (C(2)H(5)COOH)
      was observed, indicating EDTA (oxidation number for carbon is 2) was oxidized to
      propionic acid (oxidation number for carbon is 3). Nitrogen species was also
      measured and the nitrogen in EDTA was converted to ammonium instead of nitrate
      and nitrite.

PMID- 18725737
TI  - An integrated approach in a municipal WWTP: anaerobic codigestion of sludge with
      organic waste and nutrient removal from supernatant.
AB  - Co-digestion appears to be an interesting solution to increase the biogas
      production of poorly performing under-loaded digesters of waste activated sludge.
      In the Florence WWTP anaerobic codigestion could increase nitrogen and phosphorus
      loading rates and thus lower the nutrient removal efficiency. In order to develop
      an integrated solution to upgrade the Florence WWTP, the different process units
      were tested in experimental plants. Anaerobic codigestion with source-collected
      organic solid waste in a pilot-scale bioreactor showed an increase of GPR from
      0.15 to 0.45 Nl biogas/l/d with 23% of organic waste loaded. Autotrophic nitrogen
      removal was carried out in two lab-scale pilot plants which were fed with a real
      anaerobic supernatant after phosphate removal via struvite formation. The
      nitritation MBBR has been working for one year at steady-state conditions with a
      perfect nitrite/ammonium ratio equal to 1:1. Anammox biomass enrichment was
      performed in a suspended biomass SBR and the specific nitrogen removal rate
      increased from 1.7 to 58 gN/kgVSS/d in 375 days.

PMID- 18725738
TI  - Study on control of micro-pollutants by BAC filtration.
AB  - The objective of this research was to evaluate removal efficiency of micro
      pollutants in a BAC filter that followed ozonation for long term operation. The
      experimental results showed that after continuous operation for one year BAC
      filter still maintained a removal of 15 approximately 20% for COD(Mn) and 20
      approximately 30% of removal for UV(254). Correlative analysis based on lots of
      data found that empty bed contact time (EBCT) instead of flow rate could
      obviously impact on removal effect of micro-pollutants in BAC filter. And the
      optimal relationship between EBCT and removal effect of micro-pollutants for BAC
      filter was logarithm. On the other hand, long term running of BAC filter proved
      that there was a good removal of chloroform formation potential, but the removal
      of brominated trihalomethane formation potential decline with further
      bromization, even there appeared to be formation of bromoform in BAC filter.

PMID- 18725739
TI  - Comparison of two molecular methods used for subtyping of Legionella pneumophila
      1 strains isolated from a hospital water supply.
AB  - The results of the pulsed-field gel electrophoresis and the sequence-based typing
      (using the loci flaA, pilE, asd, mip, mompS and proA) were compared for subtyping
      of Legionella pneumophila 1 strains isolated from a hospital water supply.
      Molecular typing was carried out on 61 isolates (38% of the positive samples)
      selected on space and temporal criteria in order to follow the evolution of the
      water-system colonization. For all the 61 isolates, the sequence of the amplified
      mip gene fragment identified Legionella pneumophila strain Wadsworth. Genotype
      testing by PFGE analysis showed three different patterns, correspondent to three
      SBT types according to the allelic profiles. Both PFGE and SBT indicated the
      circulation and the persistence in the hospital potable water-system of three
      types randomly distributed in space and time. The two molecular methods adopted
      showed a 100% concordance, although a low degree of genetic heterogeneity
      characterized the isolates. The electrophoretic patterns were sufficiently
      unambiguous to consider PFGE a highly discriminatory typing method, but the SBT
      technique besides accurately characterizing isolates, was able to identify
      Legionella strains through analysis of the mip gene. A typing method with this
      level of discriminatory power has great potential for assisting in
      epidemiological studies.

PMID- 18725740
TI  - Modeling anaerobic digestion of dairy manure using the IWA Anaerobic Digestion
      Model no. 1 (ADM1).
AB  - The Anaerobic Digestion Model No. 1 (ADM1) can be used to describe treatment of
      dairy manure once manure characteristics have been incorporated in the model. In
      this paper a parameter set is presented that can be used with ADM1 for simulation
      of dairy manure digester performance. Model results have been verified with bench
      scale experiments and reported data from full-scale systems. Model predictions
      fit experimental data best for biogas composition and digester effluent COD.
      Simulated biogas productions were inconsistent with measurements from three
      different digesters. The model overpredicted acetogenesis, resulting in higher
      simulated than observed acetate concentrations. However, total volatile acid
      concentrations were simulated reasonably well. The model consistently predicted
      higher inorganic nitrogen than measured or reported results, indicating a need
      for further research in that area. The presented model and associated parameter
      set can be used to simulate and optimize the performance of full-scale dairy
      manure digesters.

PMID- 18725741
TI  - Marine macroalga Sargassum horneri as biosorbent for heavy metal removal: roles
      of calcium in ion exchange mechanism.
AB  - Brown seaweed Sargassum horneri, a troublesome biomass scattered along the
      seashore, was utilized as a biosorbent for Pb(II) removal from aqueous solutions.
      The Pb(II) adsorption by brown seaweed was enhanced by pretreatment with CaCl(2),
      and the Langmuir adsorption isotherm equation showed a maximum capacity of a
      Q(max) of 0.696 mmol/g and a b value of 94.33 L/mmol. Results obtained from the
      mass-balance equation derived from the simulation model of the Langmuir
      adsorption isotherm suggested that the adsorption performance of brown seaweed
      biosorbent was sufficient to reduce the concentration of Pb(II) to meet the range
      of WHO guideline. The mechanism, as elucidated using pH monitoring, adsorption
      rate and ion exchange model, involved the rapid pH change of metal solutions that
      led to high reaction rate and Pb(II) uptake in the first 30 min of the
      biosorption process. The energy X-ray analysis's result confirmed the sharp
      reduction of calcium content in the biosorbent after Pb(II) adsorption. The
      amount of calcium ions released from the biosorbent was about 1.5 times the
      amount of Pb(II) adsorbed and proved the role of calcium in the ion exchange
      mechanism. These adsorption equilibrium and mechanistic studies provide useful
      information for system design and performance prediction of biosorption
      processes.

PMID- 18725742
TI  - Assessing crucial stress on life cycle of fish in suburban streams.
AB  - To assess crucial stresses to fish survival in suburban streams, a Life Cycle
      Risk Assessment (LCRA) was developed and verified by comparing with field survey
      results. In LCRA, 8 stresses produced by human activities were taken into
      consideration, referring to the literature. Field survey was conducted over 2
      years to identify the present existence and distributions of fishes in 3 streams,
      which have different pollution levels and morphologies. Field survey results
      demonstrated that species of fishes and their populations were different in 3
      streams and varied with location. Crucial stresses frequently identified by the
      LCRA were depletion of dissolved oxygen (DO), disappearances of habitats (e.g.
      deep and shallow), disappearance of spawning area, and existence of obstructions
      in the streams. Furthermore, most LCRA results regarding existence or non
      existence of 15 fishes at 7 different sites were fairly in good agreement with
      field survey results. From these results, we concluded the present LCRA would be
      a useful tool in assessing crucial stress as well as in predicting fish species
      that are able to survive in streams.

PMID- 18725743
TI  - Kasza: design of a closed water system for the greenhouse horticulture.
AB  - The need for a closed and sustainable water system in greenhouse areas is
      stimulated by the implementation in the Netherlands of the European Framework
      Directive. The Dutch national project Kasza: Design of a Closed Water System for
      the Greenhouse Horticulture will provide information how the water system in a
      greenhouse horticulture area can be closed. In this paper the conceptual design
      of two systems to close the water cycle in a greenhouse area is described. The
      first system with reverse osmosis system can be used in areas where desalination
      is required in order to be able to use the recycle water for irrigation of all
      crops. The second system with advanced oxidation using UV and peroxide can be
      applied in areas with more salt tolerant crops and good (low sodium) water
      sources for irrigation. Both systems are financially feasible in new greenhouse
      areas with substantial available recycle water.

PMID- 18725744
TI  - Getting ready for climate change implications for the western USA.
AB  - Water users throughout the western United States have faced supply problems from
      the conception of modern civilization. Today, climate change, population growth,
      and declining water quality combine with the age-old problem of finding
      sufficient water resources in a region with a largely arid climate. Climate
      change in particular poses a significant threat to the sustainability of water
      supplies in the western United States (the West). Casting aside all debate about
      who and what is responsible for climate change, the public and water utilities
      alike must be prepared to address its effects on water supplies.

PMID- 18725745
TI  - Use of chitosan for chromium removal from exhausted tanning baths.
AB  - A novel approach, based on chitosan heavy-metal sequestrating ability, is
      proposed for chromium(III) removal from spent tanning liquor. Experimental
      results, obtained at lab-scale using real wastewater, are presented and
      discussed. Resulting efficiencies are extremely high, and strongly dependent on
      chitosan dose and pH value. Comparative analyses with other polysaccharides is
      also carried out showing that amine groups are more efficient than carboxyl and
      sulphate ones. Chromium recovery from sorption complexes and chitosan
      regeneration is finally proposed to optimize the whole process.

PMID- 18725746
TI  - Mutagenic fate of insecticide fenitrothion in the environment-mutagenicity
      increases both by anaerobic biodegradation and photodegradation.
AB  - In the present study, our objectives were (1) using the Ames assay, to evaluate
      the change in mutagenicity of a fenitrothion-containing solution during aerobic
      biodegradation, anaerobic biodegradation, and photodegradation, and (2) to
      identify possible mutagenic transformed products (TPs) that contributed
      substantially to any increase in mutagenicity. Mutagenicity of the fenitrothion
      containing solution did not increase during aerobic biodegradation with any of
      the tested bacterial strains. In contrast, the mutagenicity increased for strain
      YG1029 during anaerobic biodegradation because of the generation of a strongly
      mutagenic TP, amino-fenitrothion. During photodegradation, mutagenicities
      increased slightly for YG1021 and YG1024, possibly owing to the production of a
      previously unreported mutagenic TP.

PMID- 18725771
TI  - Rifle wounds: a review of range and location as pertaining to manner of death.
AB  - Given the prevalence of rimfire and centerfire rifle usage in both suicidal and
      homicidal cases, there is a paucity of articles in the literature that focus
      specifically on rifle wounds. Gunshot wounds, in general, have been extensively
      studied with articles focusing on the types of injuries, weapons used, wound
      locations and weapon range. We designed a study to examine the characteristics of
      rifle wounds, including both centerfire and rimfire rifles, especially pertaining
      to location and range of the wound. All deaths due to rifles examined at the
      Bexar County Medical Examiner's Office between 1988 and 2004 were reviewed. A
      total of 509 cases were identified, with 233 suicides and 266 homicides. We found
      that the average age of suicide victims (41.6 years) tended to be older than that
      of homicide victims (32.6 years). Suicides tended to be contact wounds to the
      head whereas homicides most often had multiple wound locations sustained from a
      distant range. The most common location to the head of suicidal wounds was
      intraoral whereas homicidal head wounds were more often to the temporoparietal
      region. We developed odds ratios for assessing the manner of death given a wound
      location or range; however, we caution that every case should be analyzed based
      upon it's unique circumstances and not solely its statistical probability.

PMID- 18725772
TI  - The timing of histologic changes in liver lacerations.
AB  - Microscopic examination was performed on 55 cases of traumatic liver lacerations
      incurred from fatal motor vehicle accidents. None of the deaths was due to the
      liver injury. In 38 of 55 cases, the decedent was pronounced dead at the scene.
      Microscopic examination of the liver lacerations in these 38 cases revealed no
      histologic changes related to the trauma. In 17 of 55 cases, the decedent was
      transported to the emergency room (ER) with a "survival time" (from Emergency
      Medical Service arrival to the time of pronouncement) of 15 minutes to 7 hours
      and 10 minutes. Nine of these 17 had vital signs at the scene. Five of the 17 had
      neutrophilic infiltration and hepatocyte necrosis at the site of the laceration.
      Four of these had vitals signs at the scene. Survival time of the 5 patients with
      a vital reaction at their liver injury ranged from 51 minutes to 7 hours and 10
      minutes.

PMID- 18725773
TI  - Nonnatural deaths of adolescents and teenagers: Fulton County, Georgia, 1985
      2004.
AB  - CONTEXT: Childhood deaths are carefully scrutinized by many different government
      agencies, fatality review panels, researchers, and other groups. Many such
      deaths, especially those that involve external causes such as injury and
      poisoning, are amenable to prevention. Characterizing the causes and
      circumstances of nonnatural childhood deaths may provide information that is
      useful for development of prevention strategies and programs. METHODS: This is a
      retrospective review of all nonnatural deaths investigated and certified by the
      Fulton County Medical Examiner involving persons 10 to 19 years of age during the
      years 1985-2004, inclusive. Cases were identified by searching electronic death
      investigation files maintained during the study period. Demographic and
      circumstantial information were tabulated for homicides, suicides, motor-vehicle
      fatalities, and other accidental deaths, and crude death rates were calculated
      for each 5-year period during the study. RESULTS: During the 20 year period there
      were 961 nonnatural deaths among persons 10 to 19 years of age. Most deaths were
      due to homicide (48%) followed by motor-vehicle fatalities (30%), suicide (12%),
      and nontraffic accidental fatalities (10%). Black males had the highest death
      rates among the homicide, suicide, and nontraffic accidental deaths, although the
      rates for each of these were lower in the most recent 5 year period than the
      first 5-year period. The number of deaths increased in each category as age
      increased, and this observation was most marked for homicides and least marked
      for nontraffic accidental deaths. Firearms were involved in 88% of homicides and
      61% of suicides. Most nontraffic accidental deaths were due to water-related
      accidents, followed by drug and/or alcohol toxicity, fire-related injuries, and
      accidental firearms injuries. CONCLUSIONS: Homicide accounts for almost half of
      all deaths among persons 10 to 19 years of age. Black males are at particularly
      high risk for nonnatural death in comparison with other race/sex groups,
      especially for homicide. If effective firearm fatality prevention strategies and
      programs could be implemented, data in this study suggests that such a measure
      alone could cut in half the nonnatural mortality rate in the 10 to 19 year age
      group in Fulton County. Although homicide and suicide rates have declined, there
      remains room for improvement in these areas, as is the case for traffic-related
      and other accidental fatalities.

PMID- 18725774
TI  - Investigative and autopsy findings in sport aircraft-related deaths in southwest
      Florida.
AB  - Aircraft designated for sport or recreational use only, including ultralights,
      experimental aircraft and light-sport aircraft, have become increasingly popular.
      Because of their relative safety and the rarity of fatalities resulting from
      crashes of these aircraft, the forensic literature contains little information
      concerning the pathologic findings in such deaths. We report 9 deaths resulting
      from 6 sport aircraft crashes in southwest Florida, 6 pilots and 3 passengers.
      The vehicles involved 3 experimental aircraft, 1 ultralight and 2 "ultralight
      like" aircraft. The patterns of injuries included trauma predominantly to the
      chest (3 cases), abdomen (1) or head (1), as well as multiple blunt force
      injuries involving the chest and abdomen (1) or the head and torso (3). Extremity
      fractures were found in only 2 cases, whereas injuries to the symphysis pubis
      were found in six. No "control-type" injuries were identified. These cases
      illustrate the varied pathologies associated with deaths due to crashes of sport
      aircraft and reveal the lack of uniformity associated with the investigations of
      such deaths.

PMID- 18725775
TI  - Homicides committed by youth assailants: a retrospective study.
AB  - The pediatric population has received considerable attention in the forensic
      community; the youth assailant of homicide, however, is understudied. The authors
      retrospectively reviewed all cases referred to the Forensic Pathology Section of
      the Medical University of South Carolina between January 1991 and May 2006. Cases
      included in the study were homicides in which 1 or more assailants were 19 years
      of age or younger. The cases were examined as to the cause and manner of death,
      victim age, gender, race, incident location, weapon used, assailant-victim
      relationship, assailant age, gender, race, motive, and postmortem toxicology
      results. Assailant information was obtained from forensic records at Medical
      University of South Carolina, police department records, and online search
      engines of South Carolina State newspaper archives confirmed by law enforcement
      reports. The youth assailants were predominantly black men, 15 to 19 years of age
      (range, 4-19 years). Most victims were black male acquaintances, and the motive
      was most often an argument. The most common cause of death was cerebral
      laceration because of a gunshot wound. The incident occurred in the home in 41%
      of cases, followed by the street in 31%. Victim toxicology was frequently
      positive for cocaine, marijuana, and alcohol.

PMID- 18725776
TI  - Accidental drug deaths in Fulton County, Georgia, 2002: characteristics, case
      management and certification issues.
AB  - BACKGROUND AND OBJECTIVES: Historically, the duty of the medical examiner in
      assigning cause and manner of death in drug-related death cases has been fraught
      with controversial challenges. The lack of standardization in certifying drug
      related deaths may involve differences among practicing forensic pathologists in
      their approach to such cases. The central objectives of the present study include
      characterization of current drug death patterns and the variability among medical
      examiners with respect to autopsy performance and death certification practices
      in one county medical examiner's office. MATERIALS AND METHODS: Death
      certificates, scene information/investigative reports, autopsy reports, and
      toxicological laboratory results for each of the 100 cases of drug-related death
      occurring in 2002 in Fulton County, Georgia were reviewed. Comparison of overall
      autopsy rates and autopsy rates in drug-related death cases for each medical
      examiner individually and for the group collectively was performed. In examining
      cocaine-related deaths (most common), statistical analysis was performed for
      comparison of drug concentrations (cocaine and benzoylecgonine) between deaths
      certified as cocaine toxicity (poisoning) versus cocaine-complicating disease or
      causing an adverse event such as cerebral hemorrhage. RESULTS: Causes of
      accidental drug deaths included cocaine 40%, mixed drug intoxication 37%, opioids
      10%, ethanol 7%, and prescription medication (nonopioid) 5%. Overall total
      autopsy rates in 2002 for each of the 6 independent medical examiners ranged from
      51% to 69% (mean 64%), whereas autopsy rates in drug-related death ranged from
      55% to 91% (mean 81%). In review of the subset of 40 cocaine-related deaths, 25%
      were certified as cocaine toxicity (poisoning), with the remaining 75% certified
      as cocaine-complicating disease or causing and adverse event. Autopsy rates in
      cocaine-related deaths were as follows: cocaine toxicity 80%, cocaine
      complicating disease 77.3%, and cocaine causing adverse event 62.5%. Thirty-eight
      percent of cocaine-related deaths were considered to be of "low suspicion" for
      drug involvement at the time the death was reported to the medical examiner with
      the remaining 62% being of "high suspicion". Autopsy rates were somewhat lower in
      the low suspicion group (67%) versus the high suspicion group (72%). Comparison
      of drug levels between cocaine-related death certification groups was performed.
      No statistically significant difference was shown in drug levels (cocaine, P >
      0.3; benzoylecgonine, P > 0.2) between deaths certified as cocaine toxicity
      versus those certified as cocaine-complicating disease or causing adverse event.
      CONCLUSIONS: In Fulton County, accidental drug deaths in 2002 most often involved
      cocaine either alone or in combination with opiates and/or alcohol. Cocaine,
      opiates, or both were involved in greater than three-fourths (77%) of all drug
      related deaths. The majority of all decedents were black (57%) and male (76%)
      with an average age of 42.2 years. Cocaine and ethanol were more frequently
      detected in black decedents, whereas opiates and polydrug abuse were more common
      in white decedents throughout the period studied. Preliminary investigation
      showed a high index of suspicion for the specific drug involved in virtually all
      opiate and alcohol cases, and in 62% of cocaine-related cases. Overall, the 100
      accidental drug deaths in 2002 accounted for 7.5% of all deaths investigated and
      certified by the Fulton County Medical Examiner's Office. Our study provides
      further evidence to support the lack of correlation between serum drug levels and
      the mechanism of drug toxicity in cocaine-related deaths. No statistically
      significant differences were shown in parent cocaine or benzoylecgonine
      concentrations between those cases certified as toxicities or poisonings versus
      those cases certified as aggravating underlying disease or causing an adverse
      event. In addition, 62% of the cocaine-related death cases were considered
      initially to be of high suspicion for drug-related death, thus emphasizing the
      strong importance of scene information/investigative reports in evaluating drug
      death cases and in formulating plans of action to handle each individual case.
      Among the drug-death cases handled by 6 staff medical examiners at the Fulton
      County Medical Examiner's Office, variation existed in autopsy performance and
      death certification practices. These issues are discussed in the context of the
      National Association of Medical Examiners' (NAME) Position Paper on Cocaine, NAME
      Forensic Autopsy Performance Standards, and other relevant literature. Most
      variations relate to completeness of the cause-of-death statement (whether or not
      comorbid conditions are included) rather than classification of manner of death
      within the office. However, specific wording in the cause of death may have
      significant ramifications regarding drug-related mortality statistics processed
      by the vital statistics system, with possible under-representation of drug
      related deaths in single-cause mortality data.

PMID- 18725777
TI  - Fatalities associated with the termination of electrical services.
AB  - The worldwide dependence on electricity to support the needs of today's society
      is often taken for granted and, as such, the hazards associated with the
      termination of electrical services are often neglected. Whether electrical
      services are unintentionally terminated as the result of severe weather or
      intentionally terminated as the result of nonpayment of utility bills, the
      ensuing conditions may lead to injury or death in affected individuals. We
      performed a retrospective review of all deaths investigated by the Onondaga
      County Medical Examiner's Office between 1999 and 2004. Our case database was
      searched for causes of death that included hypothermia, hyperthermia, carbon
      monoxide, fire, electrocution, and/or electricity. Further review of these cases
      was undertaken to determine the potential relationship between the death and the
      termination of electrical services. Seven fatalities were found to be associated
      with the termination of electrical services. Four fatalities resulted from its
      unintentional termination and 3 were a consequence of intentional termination. In
      reporting these deaths, we hope to emphasize the potential dangers associated
      with the termination of electrical services and explore the informational
      programs and public health laws that are in place to limit the associated
      potential negative outcomes.

PMID- 18725778
TI  - Case report of suicide by inhalation of nitrogen gas.
AB  - Nitrogen is an inert gas that is a normal constituent of the air that we breathe.
      It is a suffocating gas that does not support life and that can be a cause of
      death by the displacement of oxygen in the atmosphere. The majority of deaths
      associated with nitrogen have occurred in the setting of scuba diving. Although
      other suffocating gases have been used as a means of committing suicide, the
      literature contains little information about the use of nitrogen as a suicidal
      agent. A case of a 50-year-old man who committed suicide using a homemade suicide
      device and nitrogen gas is presented.

PMID- 18725779
TI  - Prodromal psychosis as an etiology of suicide: a case report and review of the
      literature.
AB  - Suicides without apparent antecedent causes present great difficulties for
      medical examiners and families alike. A case is presented of a young male suicide
      victim whose antemortem course did not demonstrate apparent psychopathology to
      either his family or fellow students. A journal written by the decedent was
      found, however, which revealed extensive ruminations on death, depressive
      symptomatology, and evidence of possible delusions, and hallucinations. We opine
      that this represents the prodrome of a psychotic process, possibly schizophrenia,
      and the decedent's suicide was a response to his awareness of his deteriorating
      mental status. The prodrome of schizophrenia is a well-described entity that
      manifests as a decline in social and occupational functioning, along with
      increasingly bizarre behavior. Prodromal psychosis could represent an explanation
      for some cases of suicide seemingly without causation.

PMID- 18725780
TI  - Sudden death due to congenital pericardial defect: an autopsy case.
AB  - Pericardial defects are rare in childhood and outcome is usually benign. Patients
      may be asymptomatic, but chest pain, emboli, arrhythmia, and sudden death have
      been described in the literature. We report the case of a 12-year-old boy who
      suddenly died after mild exercise. A left-sided pericardial defect with a
      diameter of 8 cm was detected on medico-legal autopsy.

PMID- 18725781
TI  - Giant cell myocarditis with cardiac tamponade: a rare combination.
AB  - Giant cell myocarditis (GCM) is a rare but fatal disease of idiopathic origin. It
      results in focal necrosis of myocardium. This is a case report of middle aged
      Malaysian Indian female who died due to cardiac tamponade due to rupture
      myocardium and tear in the root of aorta. On naked eye examination, it simply
      resembled as recent as well as old fibrotic areas of myocardial infarction. She
      was clinically diagnosed as a case of obstructive cardiomyopathy with
      atrioventricular block, and was on pace maker. There was subendocardial fibrosis
      and left ventricular transmural infarction in the left ventricle. On
      histopathology, this was diagnosed as GCM, there were widespread areas of
      inflammatory cellular infiltration within the myocardium with multinucleated
      giant cells and granulomas interspersed with lymphocytes. Microscopic field
      showed up to 10 multinucleated giant cells. In this case, there were focal areas
      at multiple locations and caused uneven thickness in the left ventricle wall.
      Idiopathic GCM is very rare and causation of hemopericardium is the unique
      feature of this case. In this case the direct link of GCM with aortitis and
      rupture of left ventricle wall resulting in hemopericardium is shown. This case
      is documented through macroscopic as well as microscopic photographs in H&E, Ziel
      Nelson, and GMS staining.

PMID- 18725782
TI  - Sudden death in a 27-year-old man with Chiari I malformation.
AB  - We present a case of a witnessed sudden death of a 27-year-old adult man with no
      antecedent trauma who subsequently was found to have a previously undiagnosed
      Chiari I malformation. Cases of sudden unprovoked respiratory collapse in
      children and adults with Chiari I malformation have been well documented, leading
      to death in some children. There have also been rare examples of sudden death in
      adults with Chiari I malformation; however, these decedents experienced recent
      trauma. This is a unique example of a witnessed sudden death of an adult with
      previously undiagnosed Chiari I malformation in the absence of trauma.

PMID- 18725783
TI  - Asphyxiating death due to basal lingual cyst (thyroglossal duct cyst) in two
      month-old infant is potentially aggravated after central catheterization with
      forced positional changes.
AB  - There are various causes of possible upper airway obstruction in infants.
      Particularly, large cysts on the base of tongue may cause severe airway
      obstruction by a mass effect on the hypopharynx and by displacing the epiglottis.
      Of these basal lingual cysts, thyroglossal duct cyst is rare but occasionally its
      remnants can be found at the base of the tongue. Although they are pathologically
      benign, basal lingual cysts may result in death by asphyxia. There are a few
      reported cases of asphyxia caused by basal lingual cyst. All died suddenly in the
      bed or cot while sleeping without any significant symptoms and signs. The authors
      experienced a unique case of death due to airway obstruction by basal lingual
      cyst (thyroglossal duct cyst), confirmed by postmortem examination, probably
      aggravated after central catheterization in 2-month-old infant who had open heart
      surgery for atrial and ventricular septal defect and report with a literature
      review.

PMID- 18725784
TI  - A case of Ludwig angina: a case report and review of the literature.
AB  - Ludwig angina is a rapidly progressing submaxillary, submandibular, and
      sublingual necrotizing cellulitis of the floor of the mouth that can have lethal
      consequences due to airway obstruction. Various aerobic and anaerobic
      microorganisms, and less often fungi, have been implicated to cause Ludwig
      angina, including oral flora such as streptococci and staphylococci. Early
      recognition and the use of parenteral antibiotics can prevent mortality and
      morbidity. We report a case of a 25-year-old white man who was admitted to the
      hospital by his dentist after being diagnosed with Ludwig angina secondary to
      periodontal abscesses involving teeth #17 and #32. Although antibiotics were
      administered, while in the hospital, the decedent had difficulty swallowing and
      was drooling. He suddenly began to have seizure-like activity thought to be
      anoxic myoclonus. The decedent was aggressively resuscitated and taken to the
      operating room for neck exploration and a tracheostomy. Neck exploration revealed
      severe necrotizing acute inflammation of the deep soft tissues and musculature of
      the neck. He remained on life support for 7 days until he was declared brain
      dead. Ludwig angina is a progressive cellulitis that often results in death by
      asphyxia. Ludwig angina can be complicated by subsequent deep neck infection. The
      underlying etiologies and common scenarios are examined, and significant autopsy
      findings and dissecting procedures are discussed. The pathophysiology of Ludwig
      angina is studied with a review of the current literature.

PMID- 18725785
TI  - Death related to nasal surgery: case report with review of therapy-related
      deaths.
AB  - The investigation of deaths that are suspected to be related to medical therapy
      present several challenges for the forensic pathologist. In all such cases, it is
      important for the pathologist to understand the therapy/procedure that may have
      played a role in death. As such, review of medical records and possible
      consultation with various medical specialists before autopsy can provide valuable
      information to ensure proper evaluation in any given case.Herein, we describe a
      rare death occurring as a complication of septoplasty, nasal polypectomy, and
      intranasal endoscopic ethmoidectomy, which are common surgical procedures
      performed by otolaryngology/head and neck surgeons. An otherwise healthy 58-year
      old woman underwent the elective surgical procedures for a deviated nasal septum,
      multiple nasal polyps, and chronic ethmoid sinusitis. Following surgery, the
      patient never awoke from general anesthesia, and further evaluation before death
      revealed a basilar subarachnoid hemorrhage. Autopsy disclosed basilar
      subarachnoid hemorrhage, a traumatic defect of the right cribiform plate, and
      associated anterior cerebral artery injury with frontal lobe damage. No vascular
      anomalies were present. The cause of death was attributed to complications
      related to nasal surgery, and the manner of death was ruled "accident."Following
      the presentation of this case, the authors discuss these common nasal surgical
      procedures, including a summary of their known complications. In addition, the
      authors address and review the topic of deaths related to medical therapy.

PMID- 18725786
TI  - The concept of forensic emergency medicine as illustrated by an unusual
      complication of pulmonary artery catheterization.
AB  - Forensic pathologists are regularly confronted with emergency and invasive
      medical procedures performed on critically ill or traumatized patients. Basic
      knowledge of such procedures and their possible complications is therefore
      mandatory in medico-legal practice. In this article, we describe a very unusual
      complication of pulmonary artery catheterization: through-and-through perforation
      of the carotid artery, initially without hemodynamic consequence. Death resulted
      from an aggravation of the preexisting cerebral edema (secondary to a
      craniocerebral trauma). The misplacement of the pulmonary artery catheter was
      clinically missed because the guidewire was initially deflected on the cervical
      spine towards the subclavian vein where the catheter--by chance--entered the
      circulatory system and followed its normal route further. The forensic importance
      of leaving all invasive medical devices in situ on a deceased person when a
      medico-legal autopsy is to be expected and the mutual interaction between
      emergency and forensic medicine (forensic emergency medicine) are discussed.

PMID- 18725787
TI  - An unusual death by transcranial stab wound: homicide or suicide?
AB  - Penetrating stab wounds of the brain are uncommonly seen in modern times and
      occur almost exclusively in homicides. We report an unusual death by self
      stabbing. A 24-year-old man was found dead at home, the handle of a kitchen knife
      protruding from his forehead. Data such as the psychiatric history of the victim,
      the multiplicity and site of wounds, the implement used, the presence of
      hesitation, and defense wounds were studied to elucidate the manner of death, and
      the suicidal nature of the event was established after police investigation.
      Atypical injuries require a careful forensic investigation, and medico-legal
      aspects of the differentiation between homicide and suicide are discussed in this
      particular case. A review of the literature revealed few cases of suicidal
      transcranial stab wounds.

PMID- 18725788
TI  - Perforation of the superior vena cava during ECMO catheterization in two neonates
      with congenital diaphragmatic hernia: a cause of accidental death.
AB  - Congenital diaphragmatic hernia (CDH) is a defect seen in approximately 1 in 3500
      live births. A complication of CDH is the herniation of abdominal contents into
      the chest cavity through the defect, which may prevent normal intrauterine
      development of the lungs. The resultant pulmonary hypoplasia and pulmonary
      hypertension causes respiratory distress in the newborn, usually requiring some
      form of intervention before the defect is surgically corrected (Embryology for
      Surgeons. Baltimore, MD: Williams & Wilkins; 1994:491-539). Extracorporeal
      membrane oxygenation, which involves cannulation of the superior vena cava (SVC),
      is often used to manage these infants. However, the mediastinal shift that often
      occurs with CDH can cause an abnormal acute angulation of the SVC, which during
      cannulation can result in trauma and possible perforation of the SVC. We present
      2 autopsy cases where the infants accidentally died as a result of extracorporeal
      membrane oxygenation cannulation.

PMID- 18725789
TI  - An unusual cause of sudden child death.
AB  - Since the rise of HIV/AIDS in Sub-Saharan Africa, there has been a massive
      promotion of condom use. Unfortunately, this promotion has not always been
      accompanied with instructions for safe use. In this case report, we describe a
      small child who aspirated a condom and subsequently died.

PMID- 18725790
TI  - Vertebral artery rupture in a sudden death case after mild trauma.
AB  - We report a case of subarachnoid hemorrhage at the skull base with possible
      rupture of a vertebral artery, and we present a new method to investigate rupture
      of this artery. In this method, the brain stem and cerebrum are divided with
      ligation of the internal carotid artery and basilar artery, and milk is injected
      from the original part of the vessel to find the rupture. We show that this
      method is particularly useful for cases of subarachnoid hemorrhage at the skull
      base in which there may be rupture of a vertebral artery.

PMID- 18725791
TI  - Atherosclerosis: a medicolegal tool in exhumed decomposed bodies.
AB  - An exhumed body of 40-year-old Hindu man was brought for repostmortem after 10
      days of death with history of allegation of assault by mob. The body was in the
      advanced stage of decomposition with adipocere formation over chest, thigh, and
      arms. In the present case, atherosclerosis was present in the coronaries and
      aorta sufficiently enough to deduce the cause of death and to substantiate the
      first autopsy findings even in highly decomposed exhumed body.

PMID- 18725793
TI  - Tuberculosis in the developing world: recent advances in diagnosis with special
      consideration of extensively drug-resistant tuberculosis.
AB  - PURPOSE OF REVIEW: Globally tuberculosis is mainly diagnosed by sputum smear
      microscopy, which fails to detect half of all cases and fails to identify drug
      resistance. Inadequate global tuberculosis control through the directly observed
      therapy short course strategy alone and the growing threat of multidrug-resistant
      and extensively drug-resistant tuberculosis has driven recent development of new
      commercial and noncommercial tests, which are most desperately needed in resource
      limited, high-burden settings. This review outlines the range of options
      currently available, highlighting particularly those recent developments with
      greatest potential for addressing the growing multidrug-resistant and extensively
      drug-resistant disaster as it affects those communities least technically and
      financially capable of controlling it. RECENT FINDINGS: Simplification of
      molecular-diagnostic techniques, rapid-liquid culture and the use of colorimetric
      indicators have improved the sensitivity, speed and reliability of tuberculosis
      and multidrug-resistant tuberculosis detection, while decreasing cost and
      bringing diagnosis closer towards (though still some way from) the point-of-care.
      SUMMARY: Global tuberculosis control in 2008 demands the use of new tools for
      more sensitive and rapid detection of active disease and of drug resistance.
      Improved technologies are available for reference laboratories but for settings
      where resources and technical capacity are limited there is little ready for
      field implementation. The pipeline is promising, but in the interim wider use of
      liquid culture and manual or colorimetric drug susceptibility testing should be
      promoted.

PMID- 18725794
TI  - Tick-borne encephalitis virus, ticks and humans: short-term and long-term
      dynamics.
AB  - PURPOSE OF REVIEW: Much public health concern and scientific interest has been
      kindled by significant increases in incidence of tick-borne encephalitis over the
      past 1-2 decades. It is the most important vector-borne disease of humans in
      Europe, for which excellent long-term data allow robust quantitative analyses.
      RECENT FINDINGS: Despite the increasing tendency to attribute all increases in
      vector-borne diseases to climate change, there is no convincing evidence that the
      appearance of new foci in Sweden, Switzerland, France and Germany during this
      century, or the upsurge in cases within well recognized endemic regions, is due
      to the recorded minor extensions of infectious ticks into higher altitudes and
      latitudes and into winter periods, in response to warmer conditions. Rather,
      there is now good evidence of greater human exposure to infected ticks through
      altered socioeconomic circumstances (in addition to higher densities of tick
      feeding deer--not reviewed here), so far best quantified for Central and Eastern
      Europe. SUMMARY: Increased awareness of tick-borne encephalitis and understanding
      of the changing risk factors, including the role of human behaviour, will ensure
      better personal protection against infection, including vaccination and avoidance
      of high-risk activities.

PMID- 18725796
TI  - Chagas disease and the US blood supply.
AB  - PURPOSE OF REVIEW: To describe new developments in blood-bank screening and
      management of patients with chronic Trypanosoma cruzi infection in the United
      States. RECENT FINDINGS: The first US Food and Drug Administration licensed
      serological test for T. cruzi blood screening went into widespread usage in
      January 2007. More than 500 confirmed T. cruzi-infected donations were detected
      by mid-June 2008. Until recently, drug therapy was recommended for acute and
      congenital infections, but seldom for chronic infections, which were believed to
      respond poorly. However, in the 1990s, efficacy was demonstrated in two placebo
      controlled trials of benznidazole in children with chronic T. cruzi infection. In
      2006, a nonrandomized, nonblinded trial demonstrated that benznidazole treatment
      may slow progression of cardiomyopathy and decrease mortality risk in infected
      adults. SUMMARY: Blood-bank screening will continue to detect T. cruzi-infected
      donors. Based on recent data, antitrypanosomal treatment is recommended for all
      acute and congenital T. cruzi infections, reactivated infection, and chronically
      infected children. In adults aged 19-50 years without advanced heart disease,
      treatment should generally be offered; management should be individualized for
      older adults. Less toxic, more effective drugs, a sensitive, specific assay for
      response to treatment, and improved healthcare access would promote more
      effective management.

PMID- 18725795
TI  - Arginine, nitric oxide, carbon monoxide, and endothelial function in severe
      malaria.
AB  - PURPOSE OF REVIEW: Parasiticidal therapy of severe falciparum malaria improves
      outcome, but up to 30% of these patients die despite best therapy. Nitric oxide
      is protective against severe disease, and both nitric oxide and arginine (the
      substrate for nitric oxide synthase) are low in clinical malaria. Parasitized red
      blood cell interactions with endothelium are important in the pathophysiology of
      malaria. This review describes new information regarding nitric oxide, arginine,
      carbon monoxide, and endothelial function in malaria. RECENT FINDINGS: Low
      arginine, low nitric oxide production, and endothelial dysfunction are common in
      severe malaria. The degree of hypoargininemia and endothelial dysfunction
      (measured by reactive hyperemia-peripheral artery tonometry) is proportional to
      parasite burden and severity of illness. Plasma arginase (an enzyme that
      catabolizes arginine) is elevated in severe malaria. Administering arginine
      intravenously reverses hypoargininemia and endothelial dysfunction. The cause(s)
      of hypoargininemia in malaria is unknown. Carbon monoxide (which shares certain
      functional properties with nitric oxide) protects against cerebral malaria in
      mice. SUMMARY: Replenishment of arginine and restoration of nitric oxide
      production in clinical malaria should diminish parasitized red blood cells
      adherence to endothelium and reduce the sequelae of these interactions (e.g.
      cerebral malaria). Arginine therapy given in addition to conventional antimalaria
      treatment may prove to be beneficial in severe malaria.

PMID- 18725797
TI  - Recent developments leading toward a paradigm switch in the diagnostic and
      therapeutic approach to human leishmaniasis.
AB  - PURPOSE OF REVIEW: To identify recent papers showing how human and parasite
      genetics influence leishmaniasis, and how understanding of the immunopathology
      may be utilized in immunotherapy for these diseases. RECENT FINDINGS: Progress
      has been made in recent years showing the complexity within populations of
      Leishmania spp. and indicating that different strains lead to diverse clinical
      pictures and responses to treatment. Thus detection of parasite genetic tags for
      the precise identification of infecting strains, and for predictive diagnosis of
      clinical and therapeutic fates seems now possible. Host genetic loci involved in
      disease outcome have been detected, which may also be explored for better case
      management. These developments in diagnosis will demand expanding the therapeutic
      arsenal to take their expected effect. This is starting to be fulfilled by
      immunotherapies successfully employed to treat cases refractory to standard first
      line drugs, as the result of a more profound comprehension of the immunopathology
      of the leishmaniases. SUMMARY: The knowledge mounting has already helped explain
      why different patients present different forms of leishmaniasis and respond
      differently to treatment, and may be on the verge of catalyzing a major change in
      the already over a century old paradigm of diagnosing and managing these
      patients.

PMID- 18725798
TI  - New insights into Entamoeba histolytica pathogenesis.
AB  - PURPOSE OF REVIEW: Entamoeba histolytica is an important global pathogen and a
      leading cause of parasitic death worldwide. This article summarizes significant
      research findings over the last year. RECENT FINDINGS: Efforts have focused
      primarily on identification of novel virulence determinants in E. histolytica,
      transcriptional profiling during tissue invasion and stage conversion, and
      characterization of basic cell biological processes. Additionally, new techniques
      for gene silencing have been identified. SUMMARY: A comprehensive examination of
      the parasite lifestyle on a whole genome level has been undertaken, allowing
      identification of new virulence genes and signaling pathways and processes
      relevant to amebic biology.

PMID- 18725799
TI  - Recent developments in dermatological syndromes in returning travelers.
AB  - PURPOSE OF REVIEW: Dermatoses are one of the three most common healthcare
      problems in returning travelers. Knowledge of imported dermatoses among Western
      physicians is however limited. In order to provide more effective pretravel
      counseling and better posttravel diagnosis and treatment, improvement is called
      for. This review highlights the most recent developments regarding dermatological
      syndromes in returning travelers. RECENT FINDINGS: The spectrum of travel-related
      dermatoses is broad, including tropical and cosmopolitan infections as well as
      environmental skin diseases. New infections such as Panton-Valentine leukocidin
      positive Staphylococcus aureus infections have begun to emerge in returning
      travelers. Localized cutaneous leishmaniasis can be managed with multiple drug
      therapies, but precise identification of the species allows tailored therapeutic
      management. Clearer definitions of cutaneous larva migrans, a syndrome, and
      creeping eruption, a cutaneous sign, have been established lately whereas the
      term hookworm-related cutaneous larva migrans is more widely used to define the
      corresponding disease. Lastly, chikungunya has emerged as a cause of febrile
      exanthema among travelers returning from endemic areas and has to be
      distinguished from dengue and measles. SUMMARY: Bacterial infections continue to
      be the main cause of consultation in returning travelers. Most of these
      infections are cosmopolitan and are secondary to arthropod exposure. Conversely,
      tropical skin infections are less commonly observed.

PMID- 18725800
TI  - New advances in Clostridium difficile infection: changing epidemiology,
      diagnosis, treatment and control.
AB  - PURPOSE OF REVIEW: Clostridium difficile infection and Clostridium difficile
      associated diarrhea (CDAD) are growing worldwide health threats. Recent studies
      have identified new host risk factors, diagnostic approaches and therapies of
      CDAD. The present review focuses on scientific papers published in the past 18
      months in an attempt to provide the latest information on the topic. RECENT
      FINDINGS: We are seeing an increasing number of patients with Clostridium
      difficile infection developing their illness in the community, although many were
      recently discharged from a healthcare setting suggesting an acquisition of
      infection in the hospital environment. The use of gastric acid-altering drugs
      that facilitate intestinal transit of the bacteria, antibacterial drugs that
      deplete colonic flora and presence of inflammatory bowel disease are risk factors
      for CDAD. Fulminant CDAD is increasing, complicated by leukocytosis (peripheral
      white blood cell count >16,000/mm), hypoalbuminemia, renal failure and emergency
      colectomy, with overall rise in CDAD disease mortality rates. Although vancomycin
      is recommended for severe cases of CDAD, recurrence rates remain high. Control of
      Clostridium difficile infection in the hospital setting focuses on disinfection
      of the environment and antibiotic stewardship policies. Anti-Clostridium
      difficile vaccines are in development. SUMMARY: CDAD is an increasing health
      problem throughout the United States, Canada and Europe with rising mortality
      rate. Occurrence of CDAD outside of healthcare settings and in pediatric
      populations represents newly emerging problems. New treatments are needed.

PMID- 18725801
TI  - Advances in the diagnosis and treatment of hepatitis B.
AB  - PURPOSE OF REVIEW: Hepatitis B virus is responsible for much morbidity and
      mortality worldwide. Although the armament of drugs licensed for its treatment
      grows, it is increasingly apparent that the efficacy of these drugs is dependent
      upon much more that their pharmacology. RECENT FINDINGS: A better understanding
      of the natural history of chronic hepatitis B infection together with recent
      advances in the molecular biology of antiviral resistance have given added
      dimensions to physicians' decision-making thought processes. SUMMARY: The present
      review outlines the recent advances in diagnostic testing that enable a better
      understanding of an individual patient's phase of illness and also how such
      information can update treatment choices better. In the second part of this
      review, the licensed therapies and their relative merits are discussed, as is
      their role in managing resistance to antiviral therapy.

PMID- 18725802
TI  - Intestinal nematodes: disease burden, deworming and the potential importance of
      co-infection.
AB  - PURPOSE OF REVIEW: Intestinal nematodes affect the world's poorest communities
      through clinical morbidity associated with heavy infection and the economic
      consequences of reduced productivity. RECENT FINDINGS: There has been a
      significant increase in funding and global support for mass treatment programmes.
      Local epidemiology is necessary if these programmes are to target the most
      affected communities, and new mapping tools and mathematical modeling
      methodologies are identifying the high degree of spatial heterogeneity and the
      relevance of polyparasitism in estimating attributable morbidity. Recent meta
      analyses have highlighted the limited evidence base for many of the claims for
      treatment benefit. Programme evaluations are beginning to demonstrate good
      outcomes, but further work is required to assess public health benefit and
      sustainability of these campaigns. New drugs have been identified which may be
      necessary to counteract resistance; vaccine studies show early promise as a
      potentially sustainable approach in the longer term. Research on the impact of
      helminths and treatment on other diseases continues, with reassuring evidence
      that mass treatment does not increase prevalence of allergy, and potential
      treatment benefit for patients with HIV. The relationship with malaria is of
      particular concern, and further studies are needed to assess how best to
      integrate control of these diseases. SUMMARY: There has been a major scale-up of
      mass treatment in recent years. In this climate, it is vital that such programmes
      are appropriately evaluated, and that well designed controlled trials assess the
      role of deworming in other groups.

PMID- 18725803
TI  - Update on hepatobiliary flukes: fascioliasis, opisthorchiasis and clonorchiasis.
AB  - PURPOSE OF REVIEW: Hepatobiliary flukes--Fasciola, Opisthorchis, Clonorchis- are
      a major public health problem in east Asia, east Europe, Africa and Latin
      America. The present review focuses on current knowledge of clinical, diagnostic
      and treatment aspects caused by hepatobiliary flukes that can be applied to
      current protocols in endemic areas. RECENT FINDINGS: Specific risk factors and
      geographic areas for these flukes have been heavily reported recently, with
      millions of people infected worldwide. Human cases in nonendemic areas, related
      to immigration and the international food trade (i.e. raw vegetables and fish),
      have also been reported. Diagnostic imaging changes include track-like lesions
      that are a characteristic feature of acute fascioliasis on computed tomography
      scanning of the liver. Newly available diagnostic serological tests may detect
      early infection and, therefore, help reduce severe clinical complications such as
      recurrent cholangitis, cholecystitis, hepatic tumours, cysts, calcification,
      cholelithiasis, pancreatitis, most importantly, cholangiocarcinoma related to
      Opisthorchis viverrini and possibly Clonorchis sinensis, and liver fibrosis
      associated with Fasciola hepatica infections. Highly effective antiparasitic
      treatment is available for all flukes. SUMMARY: There is a better understanding
      of risk factors, clinical manifestations and complications, novel diagnosis tests
      and effective treatment, which together should help reduce the morbidity and
      mortality of these infections.

PMID- 18725804
TI  - Antimicrobial resistance in typhoidal and nontyphoidal salmonellae.
AB  - PURPOSE OF REVIEW: Increasing occurrence of antimicrobial resistance in both
      typhoidal and nontyphoidal salmonellae is a major public health problem. Recent
      studies documenting the occurrence and types of resistance, with particular
      reference to quinolones and extended spectrum cephalosporins, and new approaches
      to treatment are reviewed. RECENT FINDINGS: Community and hospital-based studies
      in different Asian and African countries show widely variable rates of resistance
      in Salmonella enterica serovars Typhi and Paratyphi A. Occurrence of multidrug
      resistance has declined in some areas, but the incidence of decreased
      ciprofloxacin susceptibility has reached high levels, particularly in the Indian
      subcontinent, and isolates with full resistance to this antimicrobial are
      increasingly reported. Similar variability in resistance rates occurs among
      nontyphoidal salmonellae, with variation between serovars and by region. There
      are reports of plasmid-mediated qnr genes and a variety of extended spectrum
      cephalosporin resistance genes in nontyphoidal serovars. Two randomized
      controlled trials report gatifloxacin as a potential treatment option in enteric
      fever caused by multidrug-resistant isolates with decreased ciprofloxacin
      susceptibility. SUMMARY: Patterns of resistance in Salmonella are constantly
      changing. Continual surveillance of resistance levels is critical for clinicians
      to keep abreast of treatment options, but it is often lacking in resource-poor
      regions of the world with the highest disease burden.

PMID- 18725805
TI  - Hepatitis E virus.
AB  - PURPOSE OF REVIEW: Hepatitis E is an emerging infectious disease. This review
      will focus on recent advances in the zoonotic transmission, global distribution
      and control of hepatitis E. RECENT FINDINGS: Hepatitis E virus infection is known
      to cause waterborne epidemics and sporadic infections in developing countries.
      Recently, there have been several reports on zoonotic foodborne autochthonous
      infections of hepatitis E in developed countries. Hepatitis E typically causes
      self-limited acute infection. Recent reports have documented hepatitis E virus
      causing chronic hepatitis and cirrhosis in patients after solid organ
      transplantation. High incidence and severity of hepatitis E in pregnant women
      have been re-confirmed. The reason for high mortality in pregnant women remains
      ill understood. A recombinant hepatitis E vaccine has been evaluated in a phase
      2, randomized, placebo-controlled trial in Nepal and was found to be well
      tolerated and efficacious. SUMMARY: There has been considerable advance in
      understanding the epidemiology of hepatitis E virus infections in western
      countries. The occurrence of chronic hepatitis in organ transplant recipients
      opens a new chapter in hepatitis E epidemiology. The report on an efficacious and
      well tolerated recombinant vaccine gives hope for control of the disease in the
      near future.

PMID- 18725806
TI  - Progress in understanding norovirus epidemiology.
AB  - PURPOSE OF REVIEW: Noroviruses are now recognized as important causes of illness,
      and their incidence, impact, or both appear to have changed in recent years. This
      review focuses on studies that provide new knowledge needed to understand their
      transmission, pathogenesis, evolutionary changes and options for control. RECENT
      FINDINGS: Noroviruses have become important causes of hospitalization for
      gastroenteritis in children worldwide, with prevalences and clinical impact in
      the same range as those observed for rotaviruses - contrary to earlier findings.
      The repertoire of viruses recognized is expanding with newly found related
      viruses in different animal species. Direct zoonotic transmission appears to be
      rare, but genetic mixing of animal and human viruses seems plausible with the
      finding that common human strains replicate in pigs and cattle. A major finding
      was the evolutionary mechanism behind the success of the GII4 strains that are
      dominant in outbreak based surveillance data. The studies in developing countries
      show that the diversity of viruses involved in these settings is broader.
      SUMMARY: The data described show that the success of noroviruses is determined by
      an intricate interplay between virus evolution and susceptibility of the host,
      both genetically and immunologically. The impact of noroviruses as cause of
      significant illness in children worldwide has been underestimated and needs to be
      taken seriously. Evidence-based prevention and intervention strategies are
      urgently needed.

PMID- 18725807
TI  - Current world literature. Tropical and travel-associated diseases.

PMID- 18725808
TI  - Emergence of resistance mutations preceding virologic failure in patients
      receiving antiretroviral therapy.

PMID- 18725809
TI  - The Influence of a HAART regimen on the expression of HIV-associated Kaposi
      sarcoma.

PMID- 18725810
TI  - Coronary artery calcification on electron beam computed tomography: a 6-year
      follow-up study of HIV-infected patients.

PMID- 18725811
TI  - Endorsement of a genocidal HIV conspiracy as a barrier to HIV testing in South
      Africa.

PMID- 18725815
TI  - HIV and cardiometabolic abnormalities: new perspectives and treatment update.

PMID- 18725816
TI  - HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular
      risk in HIV-infected patients.
AB  - It has been demonstrated that patients on highly active antiretroviral therapy
      are at increased risk for developing metabolic abnormalities that include
      elevated levels of serum triglycerides and low-density lipoprotein cholesterol
      and reduced levels of high-density lipoprotein cholesterol. This dyslipidemia is
      similar to that seen in the metabolic syndrome, raising the concern that highly
      active antiretroviral therapy also potentially increases the risk for
      cardiovascular complications. This paper reviews the contribution of both HIV
      infection and the different components of highly active antiretroviral therapy to
      dyslipidemia and the role of these abnormalities toward increasing the risk of
      cardiovascular disease in HIV-infected patients; therapeutic strategies to manage
      these risks are also considered.

PMID- 18725817
TI  - Insulin resistance and diabetes mellitus associated with antiretroviral use in
      HIV-infected patients: pathogenesis, prevention, and treatment options.
AB  - The contribution of current antiretroviral treatment regimens to the long-term
      survival of HIV-infected individuals is accompanied by increased risk of glucose
      metabolism abnormalities in this patient population. The risk of insulin
      resistance and diabetes in HIV-infected patients receiving antiretroviral
      treatment stems from 2 sources: exposure to the same environmental factors that
      have led to an increased incidence of these conditions in the general population
      and the negative effects on glucose metabolism inherent to components of
      antiretroviral treatment regimens. This article reviews the pathogenesis and
      diagnosis of insulin resistance and diabetes and the contribution of components
      of antiretroviral therapy regimens to increased risk for these conditions.
      Optimization of antiretroviral treatment regimens for HIV-infected patients with
      or at increased risk for development of abnormalities in glucose metabolism is
      discussed.

PMID- 18725818
TI  - Management of morphologic changes associated with antiretroviral use in HIV
      infected patients.
AB  - Morphological changes related to altered distribution of regional adipose tissue
      are well characterized as a potential complication of antiretroviral treatment
      regimens that can be physically disfiguring and negatively affect the quality of
      life. Lipoatrophy and lipohypertrophy often occur independently of one another,
      and the risk of developing these conditions has been associated with specific
      antiretroviral medications but can also be influenced by a number of host
      factors. This review details our current understanding of the etiologies of
      lipoatrophy and lipohypertrophy, including evidence from recent clinical trials,
      and describes strategies available to manage these conditions. The potential
      increase in risk of cardiovascular disease associated with these metabolic
      disturbances is also discussed.

PMID- 18725819
TI  - Improving colorectal cancer screening through research in primary care settings.

PMID- 18725820
TI  - Preferences for colorectal cancer screening among racially/ethnically diverse
      primary care patients.
AB  - BACKGROUND: Incorporating patients' preferences into colorectal cancer (CRC)
      screening recommendations has been identified as a potential mechanism for
      increasing adherence. This study used conjoint analysis to describe variation in
      CRC screening preferences among racially/ethnically diverse primary care
      patients. METHODS: We recruited patients ages 50-80 of a large practice-based
      research network stratified by white, African American, or Hispanic
      race/ethnicity to complete a preference assessment instrument. Participants were
      asked to rate 8 hypothetical CRC screening test scenarios comprised of different
      combinations of 5 attributes and 6 scenarios designed to depict guideline
      recommended CRC screening tests (eg, fecal occult blood test, flexible
      sigmoidoscopy, colonoscopy, and double contrast barium enema) including new
      technology (eg, virtual colonoscopy, fecal immunochemical test). Responses were
      used to calculate the overall importance of test attributes, the relative
      importance of attribute levels, and to identify factors associated with
      preferences. RESULTS: Two hundred twelve primary care patients were recruited to
      the study (74 white, 60 African American, 78 Hispanic). Of the guideline
      recommended tests, 37% preferred COL, 31% FOBT, 15% BE, and 9% SIG. Ratings of
      new technology tests were significantly (P < 0.05) higher than ratings of
      guideline-recommended tests. The order of the importance of attributes was: what
      the test involved (37%), accuracy (19%), frequency (17%), discomfort (15%), and
      preparation (13%). Part-worth utilities for 1 attribute showed that collecting a
      stool sample was most preferable and endoscopy without sedation least preferable.
      Multivariate regression found that race/ethnicity and specific test attributes
      were independently associated (P < 0.05) with test preferences. CONCLUSIONS:
      Primary care patients have distinct preferences for CRC screening tests that can
      be linked to test attributes. Racial/ethnic variations in test preferences
      persist when controlling for attributes. Tailoring screening recommendations to
      patients' preferences may increase screening adherence.

PMID- 18725821
TI  - Perceptions of Iowa family physicians regarding colorectal cancer screening.
AB  - BACKGROUND: Fewer than half of Americans have been screened for colorectal cancer
      (CRC), a largely preventable disease. METHODS: All physician members (n = 1030)
      of the Iowa Academy of Family Physicians were mailed a 3-page investigator
      developed survey about their attitudes, barriers, and practices regarding CRC
      screening. RESULTS: The usable response rate was 29%. Forty-three percent
      practiced in rural settings. Ninety-five percent felt that they were well
      informed about American Cancer Society guidelines and 90% tried to follow the
      guidelines. Most doctors (88%) disagreed with the statement that there was "no
      time to adequately discuss screening," but they would like more time to discuss
      screening. Only 40% felt their medical records were organized to easily determine
      screening status, 40% encouraged office staff to participate in screening, and
      16% had a written policy regarding CRC screening. Physicians estimated that they
      recommend screening to 78% of their patients and that 54% of their patients were
      actually up-to-date. Discussion of CRC screening was strongly dependent on visit
      type, with physicians estimating that CRC screening is discussed at 11% of acute
      visits, 42% of chronic visits, and 87% of health maintenance visits. Several
      office system factors were associated with a recommendation for screening in a
      multivariable linear regression model (R = 0.33). CONCLUSIONS: Although nearly
      all physicians felt that they were well informed about American Cancer Society
      guidelines and tried to follow guidelines for CRC screening, few had office
      systems to facilitate screening. Physicians would like more time to discuss
      screening. Office systems likely have the most potential to improve CRC screening
      among patients attending primary care practices.

PMID- 18725822
TI  - A provider intervention to improve colorectal cancer screening in county health
      centers.
AB  - BACKGROUND: Publicly-funded health centers serve disadvantaged populations who
      underuse colorectal cancer screening (CRC). Because physicians play a key role in
      patient adherence to screening, provider interventions within health center
      practices could improve the delivery/utilization of CRC screening. METHODS: A 2
      group study design was used with 4 pairs of health centers randomized to the
      intervention or control condition. The provider intervention featured academic
      detailing of the small practice groups, followed by a strategic planning session
      with the entire health center staff using SWOT analysis. The outcome measure of
      provider endoscopy referral/fecal occult blood test dispensing and/or completion
      of CRC screening was determined by medical record audit (n = 2224). The
      intervention effect was evaluated using generalized estimating equations. Pre
      post intervention patient surveys (n = 281) were conducted. RESULTS: Chart audits
      of the 1 year period before and after the intervention revealed a 16% increase
      from baseline in CRC screening referral/dispensing/completion among intervention
      centers, compared with a 4% increase among controls, odds ratio (OR) = 2.25 (1.67
      3.04) P < 0.001. Intervention versus control health center patient self-reports
      of lack of physician recommendation as a reason for not having CRC screening
      declined from baseline to follow-up (P = 0.04). CONCLUSIONS: Provider
      referrals/dispensing/completion of CRC screening within health centers was
      significantly improved and barriers reduced through a provider intervention
      combining continuing medical education with a team building strategic planning
      exercise.

PMID- 18725823
TI  - Implementing an intervention to promote colon cancer screening through e-mail
      over the Internet: lessons learned from a pilot study.
AB  - BACKGROUND: Colon cancer screening (CRCS) tests are underused. Multiple CRCS
      options may confuse patients and lead to inaction. E-mail between patients and
      physicians may raise awareness about CRCS and allow physicians to answer
      questions about test options. OBJECTIVES: To develop and implement an electronic
      intervention, the InterNet LETter (NetLET), to increase interest in and use of
      CRCS among patients with and without e-mail access at home or work. RESEARCH
      METHODS: During 2004-2005, 97 patients over 49 years old were recruited during a
      clinic visit. Patients with e-mail at home or work were assigned to the private
      access arm; patients without e-mail but willing to use the public library system
      were assigned to the public access arm. Within each arm, patients were randomized
      to the NetLET or control group. The NetLET consisted of a personalized e-mail
      from the physician reminding the patient to undergo CRCS and providing a link to
      a webpage with information about CRCS. Control groups were mailed a reminder
      letter from their physician. All were mailed a fecal occult blood test (FOBT)
      kit. RESULTS: In the public access intervention group, only 1 of 11 patients
      viewed the NetLET. In the private access intervention group, 10 of 42 viewed it.
      Eleven of 42 (26%) private access intervention group participants, and 8 of 35
      (23%) private access control group participants returned an FOBT. No public
      access intervention group patients, but 3 of 9 control group patients, returned
      an FOBT. CONCLUSIONS: We concluded that it was not feasible to implement the
      NetLET, but reasons for lack of success differed for the private and public
      access arms.

PMID- 18725824
TI  - Tailored navigation in colorectal cancer screening.
AB  - BACKGROUND: Colorectal cancer (CRC) screening is underutilized. Effective methods
      to increase screening use are needed. This study sought to determine the impact
      of tailored navigation on CRC screening in primary care. METHODS: The study
      included 154 primary care practice patients who were 50 or more years of age,
      were eligible for CRC screening, and had an office visit within 2 years before
      study initiation. Baseline telephone survey data were collected on participant
      sociodemographic characteristics, psychosocial factors, and screening test [fecal
      occult blood test (FOBT) or colonoscopy] decision stage. By comparing decision
      stage data, we identified that test with the highest decision stage (ie,
      preferred screening test). Participants who preferred FOBT were sent an FOBT kit
      and a reminder. Those preferring colonoscopy were sent colonoscopy instructions.
      After this mailing, a study patient navigator made a telephone call to guide
      participants towards screening. Six-month end point survey and medical records
      data were obtained. Univariable and multivariable analyses were performed to
      identify predictors of screening and of change in preferred screening test
      decision stage. RESULTS: At end point, 63 (41%) study participants had screened.
      From baseline to end point, overall screening preference increased for 75 (63%)
      participants. Age and perceived salience and coherence (ie, screening is
      important and sensible) were positive, significant predictors of screening use (P
      = 0.02 and P = 0.05, respectively); while only age predicted change in overall
      screening preference (P = 0.03). CONCLUSIONS: Study participant screening use and
      preference increased. Age and attitudes predicted outcomes. Randomized trials are
      needed to determine intervention impact at the population level.

PMID- 18725825
TI  - Data systems to evaluate colorectal cancer screening practices and outcomes at
      the population level.

PMID- 18725826
TI  - Implications of new colorectal cancer screening technologies for primary care
      practice.

PMID- 18725827
TI  - Practice-based research networks: laboratories for improving colorectal cancer
      screening in primary care practice.

PMID- 18725828
TI  - Modeling the decision to undergo colorectal cancer screening: insights on patient
      preventive decision making.
AB  - BACKGROUND: Little is known about how patients decide whether or not to undergo
      colorectal cancer screening. Although low screening rates evidence the outcome of
      these decisions, the processes patients use to balance benefits, risks, and costs
      with their own values and preferences are unclear. To increase screening rates,
      and ultimately save lives, it is important for providers to be aware of how
      patients make screening decisions. OBJECTIVES: The purpose of this study was to
      identify patterns of patient colorectal cancer screening decisions that might be
      supported by health care providers. POPULATION: In this study, we focused on
      people from Central Kentucky--a region with historically low screening rates.
      METHOD: We interviewed patients using a semi-structured format. Three members of
      the research team independently analyzed each interview transcript for factors
      that influenced the decision, and a pictorial representation of each decision
      process, based on Kurt Lewin's theory of decision making, was constructed for
      each participant. The individual decision processes were compared with identify
      patterns. RESULTS: Seventeen women and 13 men made up the sample. We discerned 7
      decision patterns. CONCLUSIONS: This research documents 7 patterns and identifies
      common driving and restraining forces.

PMID- 18725829
TI  - Informed decision-making and colorectal cancer screening: is it occurring in
      primary care?
AB  - BACKGROUND: Current recommendations advise patients to participate in the
      decision-making for selecting a colorectal cancer (CRC) screening option. The
      degree to which providers communicate the information necessary to prepare
      patients for participation in this process is not known. OBJECTIVE: To assess the
      level of informed decision-making occurring during actual patient-provider
      communications on CRC screening and test for the association between informed
      decision-making and screening behavior. RESEARCH DESIGN: Observational study of
      audiotaped clinic visits between patients and their providers in the primary care
      clinic at a Veterans Administration Medical Center. SUBJECTS: Male patients, age
      50-74 years, presenting to a primary care visit at the study site. MEASURES: The
      Informed Decision-Making (IDM) Model was used to code the audiotapes for 9
      elements of communication that should occur to prepare patients for participation
      in decision-making. The primary outcome is completion of CRC screening during the
      study period. RESULTS: The analytic cohort consisted of 91 patients due for CRC
      screening who had a test ordered at the visit. Six of the 9 IDM elements occurred
      in < or =20% of the visits with none addressed in > or =50%. CRC screening
      occurred less frequently for those discussing "pros and cons" (12% vs. 46%, P =
      0.01) and "patient preferences" (6% vs. 47%, P = 0.001) compared with those who
      did not. CONCLUSIONS: We found that a lack of informed decision-making occurred
      during CRC screening discussions and that particular elements of the process were
      negatively associated with screening. Further research is needed to better
      understand the effects of informed decision-making on screening behavior.

PMID- 18725830
TI  - Meeting the needs of diverse populations: an overview and commentary.

PMID- 18725831
TI  - Increasing patient/physician communications about colorectal cancer screening in
      rural primary care practices.
AB  - BACKGROUND: Rural populations as well as less educated people in the United
      States are less likely to receive colorectal cancer (CRC) screening than people
      living in urban areas and more educated people. METHODS: We tested a computer
      tablet, Patient/Provider Communication Assistant (PPCA), which collected data,
      educated patients, and printed personalized notes to patients and providers
      encouraging conversation about CRC screening. Mixed model analyses using a
      prepost quasi-experimental design compared patient results during the comparison
      and intervention periods in 5 rural primary care practices on provider discussion
      about CRC screening, provider recommendation, and patient intention to be
      screened. Models including age, education, and literacy measures as covariates
      were examined. RESULTS: Providers talked with patients about CRC screening in
      general, and colonoscopy specifically more frequently after the PPCA than with
      the comparison group (P values = 0.04 and 0.01, respectively). Providers
      recommended CRC screening more often to patients in the intervention group than
      to the comparison group (P = 0.02). Patients planned to be screened, specifically
      with colonoscopy, more frequently after the intervention than in the comparison
      group (P = 0.003). There were no interactions between group and any of the
      covariates. Ninety-five percent of the patients, regardless of age or education,
      found the PPCA easy to use. CONCLUSIONS: Results indicated increased provider
      discussion and recommendation, and patients' intentions to obtain CRC screening,
      and in particular colonoscopy, for patients exposed to the intervention,
      regardless of the patients' age or literacy levels. The PPCA is a promising
      intervention method that is acceptable to rural patients.

PMID- 18725832
TI  - Interactive, culturally sensitive education on colorectal cancer screening.
AB  - BACKGROUND: Increasing colorectal cancer screening (CRCS) can have a substantial
      positive impact on morbidity and mortality. OBJECTIVES: The purpose of this
      report is to describe the development and feasibility testing of a computer
      based, theory-guided educational program designed to increase CRCS. RESEARCH
      DESIGN: This mixed-methods study used focus groups and subsequent randomized
      controlled trial design. SUBJECTS: Participants (N = 199) were randomized to an
      intervention or control group; 75% were African American; mean age was 57.36 (SD
      = 6.8); 71% were male. MEASURES: Previously validated measures on knowledge,
      beliefs, and screening test adherence were used to establish pre- and post
      intervention perceptions. Feasibility was measured by response and completion
      rates, and participants' perceptions of the program. RESULTS: Before feasibility
      testing, the program was presented to 2 focus groups. Changes were made to the
      program based on discussion, leading to a visually appealing, easy to understand
      and navigate, self-paced program. In the RCT pilot test that followed, of the
      participants in the intervention group, 80% said the education helped them decide
      to get CRCS; 49% agreed it helped them overcome barriers; 91% agreed it was
      useful, 68% thought it raised new concerns about cancer, but only 30% said it
      made them worry about CRC; 95% agreed their doctor's office should continue
      giving such education, and 99% said they would inform family about the program.
      CONCLUSIONS: The response rate of 83% demonstrated feasibility of conducting
      colorectal cancer education in the primary care setting; overall the program was
      well received; participants averaged 23 minutes to complete it. Participants
      sought no help from attending data collectors and navigated the revised touch
      screen program with ease. Computer-based education is feasible in primary care
      clinics.

PMID- 18725833
TI  - Personalized screening for colorectal cancer.

PMID- 18725835
TI  - Innovative provider- and health system-directed approaches to improving
      colorectal cancer screening delivery.

PMID- 18725834
TI  - Development of intervention materials for individuals with limited English
      proficiency: lessons learned from "Colorectal Cancer Screening in Chinese
      Americans".
AB  - BACKGROUND: According to recent US census data, 52 million people reported
      speaking a language other than English at home, and almost 45% of this population
      reported limited English proficiency (LEP). Colorectal cancer (CRC) ranks among
      the top 3 most common cancers for several Asian ethnic groups, yet screening
      remains underutilized by Asian Americans. OBJECTIVES: This article describes the
      development of culturally and linguistically appropriate intervention materials
      for individuals with LEP. We discuss lessons learned from this research and
      implications for the translation of research into practice. METHODS: The Health
      Behavior Framework served as the conceptual model for this study, and qualitative
      findings guided the development of our intervention materials (a video and
      pamphlet). To recommend Western preventive behaviors, the research team bridged
      the gap between Western and Chinese values and beliefs by devoting particular
      attention to: (1) the target population's sociocultural values and health
      beliefs; and (2) unique linguistic features of the Chinese language. RESULTS: Key
      lessons learned from this study include the importance of: (1) a conceptual
      framework to guide intervention development; (2) incorporating sociocultural
      values and health beliefs into the intervention; (3) addressing and capitalizing
      on complex linguistics issues; (4) using qualitative methodology in cross
      cultural research; and (5) contributions from a multicultural and multilingual
      research team. Other lessons relate to the translation of research findings into
      practice. We surmise that lessons learned from this study may be pertinent to the
      promotion of CRC screening among other patient groups with LEP and applicable to
      additional cancer screening tests.

PMID- 18725836
TI  - Impact of a generalizable reminder system on colorectal cancer screening in
      diverse primary care practices: a report from the prompting and reminding at
      encounters for prevention project.
AB  - BACKGROUND: Computerized reminder systems (CRS) show promise for increasing
      preventive services such as colorectal cancer (CRC) screening. However, prior
      research has not evaluated a generalizable CRS across diverse, community primary
      care practices. We evaluated whether a generalizable CRS, ClinfoTracker, could
      improve screening rates for CRC in diverse primary care practices. METHODS: The
      study was a prospective trial to evaluate ClinfoTracker using historical control
      data in 12 Great Lakes Research In Practice Network community-based, primary care
      practices distributed from Southeast to Upper Peninsula Michigan. Our outcome
      measures were pre- and post-study practice-level CRC screening rates among
      patients seen during the 9-month study period. Ability to maintain the CRS was
      measured by days of reminder printing. Field notes were used to examine each
      practice's cohesion and technology capabilities. RESULTS: All but one practice
      increased their CRC screening rates, ranging from 3.3% to 16.8% improvement. t
      tests adjusted for within practice correlation showed improvement in screening
      rates across all 12 practices, from 41.7% to 50.9%, P = 0.002. Technology
      capabilities impacted printing days (74% for high technology vs. 45% for low
      technology practices, P = 0.01), and cohesion demonstrated an impact trend for
      screening (15.3% rate change for high cohesion vs. 7.9% for low cohesion
      practices). CONCLUSIONS: Implementing a generalizable CRS in diverse primary care
      practices yielded significant improvements in CRC screening rates. Technology
      capabilities are important in maintaining the system, but practice cohesion may
      have a greater influence on screening rates. This work has important implications
      for practices implementing reminder systems.

PMID- 18725837
TI  - Implementing colorectal cancer screening in community health centers: addressing
      cancer health disparities through a regional cancer collaborative.
AB  - BACKGROUND: The population served by Federally Qualified Health Centers (FQHCs)
      has lower levels of cancer screening compared with the general population and
      suffers a disproportionate cancer burden. To address these disparities, 3 federal
      agencies and a primary care association established and tested the feasibility of
      a Regional Cancer Collaborative (RCC) in 2005. METHODS: RCC faculty implemented a
      learning model to improve cancer screening across 4 FQHCs that met explicit
      organizational readiness criteria. Regional faculty trained "care process
      leaders," who worked with primary care teams to plan and implement practice
      changes. FQHCs monitored progress across the following measures of screening
      implementation: self-management goal-setting; number and percent screened for
      breast, cervical, and colorectal cancer; percent timely results notification; and
      percent abnormal screens evaluated within 90 days. Progress and plans were
      reviewed in regular teleconferences. FQHCs were encouraged to create local
      communities of practice (LCOP) involving community resources to support cancer
      screening and to participate in a monthly teleconference that linked the LCOPs
      into a regional community of practice. Summary reports and administrative data
      facilitated a process evaluation of the RCC. chi test and test of trends compared
      baseline and follow-up screening rates. RESULTS: The RCC taught the collaborative
      process using process leader training, teleconferences, 2 regional meetings, and
      local process improvement efforts. All organizations created clinical tracking
      capabilities and 3 of the 4 established LCOPs, which met monthly in an regional
      community of practice. Screening documentation increased for all 3 cancers from
      2005 to 2007. Colorectal cancer screening increased from 8.6% to 21.2%.
      CONCLUSIONS: A regional plan to enable collaborative learning for cancer
      screening implementation is feasible, and improvements in screening rates can
      occur among carefully selected organizations.

PMID- 18725838
TI  - Is the type of Medicare insurance associated with colorectal cancer screening
      prevalence and selection of screening strategy?
AB  - BACKGROUND: Medicare managed care (MMC) plans may be better positioned to deliver
      preventive services than fee-for-service (FFS) insurers. We assessed whether
      beneficiaries in MMC plans were more likely than those in traditional FFS
      insurance to receive colorectal cancer (CRC) screening and whether type of
      insurance was associated with use of specific screening strategies. METHODS: We
      studied 10,173 respondents to the 2000 Medicare Current Beneficiary Survey
      representing 24,394,204 US Medicare beneficiaries. We identified 4 CRC screening
      strategies: (1) interval-appropriate screening, (2) fecal occult blood testing
      (FOBT) within the past 2 years, (3) colonoscopy or sigmoidoscopy within the past
      5 years, and (4) primary invasive screening (interval-appropriate colonoscopy or
      sigmoidoscopy without FOBT). Using a propensity score model to adjust for the
      nonrandom selection of insurance based on sociodemographic characteristics and
      other respondent-reported "care-seeking" variables, we compared the adjusted
      percentage of MMC and FFS beneficiaries screened using each CRC screening
      strategy. RESULTS: In this sample, 21.6% of Medicare beneficiaries were
      continuously enrolled in MMC, 61.3% had FFS with supplemental insurance, and
      17.1% had FFS coverage alone. Just over 51% of beneficiaries received interval
      appropriate CRC screening. Interval-appropriate CRC screening was reported by
      54.7% in FFS with supplemental insurance, 52.9% in MMC, and 36.3.% in the FFS
      group without supplemental insurance (P < 0.001). Use of the FOBT strategy was
      more common in MMC compared with FFS with or without supplemental insurance.
      Adjustment for sociodemographic characteristics and care-seeking propensity had a
      sizable impact on differences in screening prevalence, but did not substantially
      alter the conclusions. CONCLUSIONS: In 2000, the type of Medicare insurance was
      associated with differences in the prevalence of interval-appropriate CRC
      screening with lower prevalence among FFS beneficiaries who lacked supplemental
      insurance. Although managed care did not produce more CRC screening than
      supplemental insurance, managed care plans seem to have encouraged FOBT testing
      over other strategies.

PMID- 18725839
TI  - Improvement in the diagnostic evaluation of a positive fecal occult blood test in
      an integrated health care organization.
AB  - BACKGROUND: Screening for fecal occult blood can be effective in reducing
      colorectal cancer mortality only if positive tests are appropriately followed up
      with complete diagnostic evaluation (ie, colonoscopy or flexible sigmoidoscopy
      with double contrast barium enema) and treatment. OBJECTIVES: To examine whether
      rates of complete diagnostic evaluation after a positive fecal occult blood test
      (FOBT) have improved over time after the implementation of tracking systems and
      physician guidelines within a large integrated health care organization. RESEARCH
      DESIGN: From 1993 to 2005, 8513 positive FOBTs were identified on 8291 enrollees
      aged 50-79 of a large health care system. Automated records were used to identify
      repeat FOBTs, colonoscopy, flexible sigmoidoscopy, and double-contrast barium
      enema within 1 year after the positive FOBT. National rates of complete
      diagnostic evaluation were estimated from the 2005 National Health Interview
      Survey. RESULTS: In this integrated health care organization, the percentage of
      positive FOBTs followed by complete diagnostic evaluation within 1 year increased
      from 57-64% in 1993-1996 to 82-86% from 2000-2005. Use of repeat FOBT after a
      positive FOBT decreased from 28-31% in 1993-1996 to 6-11% in 2000-2005. Based on
      the National Health Interview Survey, only 52% of positive FOBTs in 2000-2005
      were followed by complete diagnostic evaluation nationally. CONCLUSIONS:
      Adherence to recommendations for complete diagnostic evaluation after a positive
      FOBT has greatly improved over time in an integrated group medical practice.
      Through the use of tracking systems and screening guidelines, it may be possible
      to reach levels of follow-up that are comparable to those observed in randomized
      trials.

PMID- 18725840
TI  - Evaluating approaches to increase uptake of colorectal cancer screening: lessons
      learned from pilot studies in diverse primary care settings.

PMID- 18725841
TI  - Do surgical quality gaps cause healthcare disparities?

PMID- 18725842
TI  - Socioeconomic status and surgical mortality in the elderly.
AB  - BACKGROUND: Although racial disparities in the quality of surgical care are well
      described, the impact of socioeconomic status on operative mortality is
      relatively unexplored. METHODS: We used Medicare data to identify all patients
      undergoing 1 of 6 common, high risk surgical procedures between 1999 and 2003. We
      constructed a summary measure of socioeconomic status for each US ZIP code using
      data from the 2000 US Census linked to the patient's ZIP code of residence. We
      assessed the effects of socioeconomic status on operative mortality rates while
      controlling for other patient characteristics and then examined the extent to
      which disparities in operative mortality could be attributed to differences in
      hospital factors. RESULTS: Socioeconomic status was a significant predictor of
      operative mortality for all 6 procedures in crude analyses and in those adjusted
      for patient characteristics. Comparing the lowest quintile of socioeconomic
      status to the highest, the adjusted odds ratios (OR) and 95% confidence intervals
      (CI) ranged from OR = 1.17; 95% CI: 1.10-1.25 for colectomy to OR = 1.39; 95% CI:
      1.18-1.65 for gastrectomy. After further adjustment for hospital factors, the
      odds ratio associated with socioeconomic status for coronary artery bypass (OR =
      1.14; 95% CI: 1.09-1.19), aortic valve replacement (OR = 1.13; 95% CI: 1.04
      1.23), and mitral valve replacement (OR = 1.11; 95% CI: 1.00-1.23) were
      diminished, and those for lung resection (OR = 0.93; 95% CI: 0.81-1.07),
      colectomy (OR = 1.04; 95% CI: 0.98-1.12), and gastrectomy (OR = 1.11; 95% CI:
      0.90-1.38) were reduced and also were no longer statistically significant. Within
      hospitals, there were only small differences in adjusted operative mortality by
      patient socioeconomic status. CONCLUSIONS: Patients with lower socioeconomic
      status have higher rates of adjusted operative mortality than patients with
      higher socioeconomic status across a wide range of surgical procedures. These
      disparities in surgical outcomes are largely attributable to differences between
      the hospitals where patients of higher and lower socioeconomic status tend to
      receive surgical treatment.

PMID- 18725843
TI  - Racial disparities in term induction of labor rates in Illinois.
AB  - OBJECTIVE: To determine whether the increase in the rate of labor induction at
      term is significantly different among women of different races. STUDY DESIGN:
      Data from the National Center for Health Statistics were used to identify
      pregnant women with singletons at 37-41 weeks gestation from 1991 to 2003 in
      Illinois. The independent association between the induction rate at term and
      maternal race was evaluated using longitudinal regression. Covariates considered
      were maternal demographic and obstetrical characteristics; those that changed the
      estimated association between race and induction of labor by at least 20% were
      included in the final model. RESULTS: The mean annual induction rates rose
      significantly during the study period both for the entire population and for each
      racial group. After adjusting for maternal demographic characteristics,
      obstetrical risk factors for medically-indicated induction, and for county-level
      malpractice premium charges, each 1% increase in the proportion of the white and
      non-white/non-African American populations within a county was associated with
      significantly higher induction rates (74% and 92%, respectively) in the county.
      CONCLUSIONS: Although induction rates have increased for all women, the rate of
      rise has increased disproportionately among women of non-African American race.

PMID- 18725844
TI  - Perceived discrimination in health care and health status in a racially diverse
      sample.
AB  - BACKGROUND: Despite the surge of recent research on the association between
      perceived discrimination and health-related outcomes, few studies have focused on
      race-based discrimination encountered in health care settings. This study
      examined the prevalence of such discrimination, and its association with health
      status, for the 3 largest race/ethnic groups in the United States. METHODS: Data
      were drawn from the 2004 Behavioral Risk Factor Surveillance System survey. The
      primary variables were perceived racial discrimination in health care and self
      reported health status. Multivariable logistic regression was used to compare the
      prevalence of perceived discrimination for whites, African Americans, and
      Hispanics, and to examine the association between perceived discrimination and
      health status, controlling for sex, age, income, education, health care coverage,
      affordability of medical care, racial salience, and state. RESULTS: Perceived
      discrimination was reported by 2%, 5.2%, and 10.9% of whites, Hispanics, and
      African Americans, respectively. Only the difference between African Americans
      and whites remained significant in adjusted analyses [odds ratio (OR) = 3.22, 95%
      confidence interval (CI) = 2.46-4.21]. Racial/ethnic differences in perceived
      discrimination depended on income, education, health care coverage, and
      affordability of medical care. Perceived discrimination was associated with worse
      health status for the overall sample (OR = 1.71, 95% CI = 1.35-2.16). Stratified
      analyses revealed that this relationship was significant for whites (OR = 2.00,
      95% CI = 1.45-2.77) and African Americans (OR = 1.95, 95% CI = 1.39-2.73), but
      not for Hispanics (OR = 0.55, 95% CI = 0.24-1.22). CONCLUSIONS: Perceived racial
      discrimination in health care is much more prevalent for African Americans than
      for whites or Hispanics. Furthermore, such discrimination is associated with
      worse health both for African Americans and for whites.

PMID- 18725845
TI  - Self-rated mental health and racial/ethnic disparities in mental health service
      use.
AB  - BACKGROUND: Studies of health service use for emotional problems show that the
      majority of those with disorders do not seek professional help. In addition,
      mental health service use is lower among members of minority communities,
      compared with non-Hispanic whites. OBJECTIVE: To examine the role of self
      reported mental health as an indicator of awareness of mental conditions and as
      an influence in the process of seeking mental health care. RESEARCH DESIGN: We
      conducted cross-sectional analyses of nationally representative data from the
      Medical Expenditure Panel Survey (MEPS) for 2000-2004. MEASURES: In-person
      interviews obtained data on self-rated mental health (SRMH), ambulatory mental
      health visits, and purchase of prescription medications to treat mental
      conditions. Respondents completed the SF-12 health status survey; analyses
      included the SF-12 mental component summary (MCS) as a measure of emotional
      symptoms. Analyses included only those who provided self-reports of MCS and SRMH.
      RESULTS: SRMH was related to any ambulatory visit and any medication purchase for
      mental health treatment, controlling for MCS, and other sociodemographic and
      clinical variables. The association between SRMH and service use was weaker for
      black and Hispanic respondents than for whites. In addition, the magnitude of the
      association between SRMH and MCS was weaker for black and Hispanic respondents
      than for whites. CONCLUSIONS: Racial/ethnic differences in service use may arise
      in part from different propensities to interpret emotional symptoms as reflecting
      one's mental health and then to seek professional intervention for emotional
      problems. SRMH may be useful as an indicator of the extent to which people
      acknowledge the existence of emotional problems.

PMID- 18725846
TI  - Race/Ethnicity and patient confidence to self-manage cardiovascular disease.
AB  - BACKGROUND: Minority populations bear a disproportionate burden of chronic
      disease, due to higher disease prevalence and greater morbidity and mortality.
      Recent research has shown that several factors, including confidence to self
      manage care, are associated with better health behaviors and outcomes among those
      with chronic disease. OBJECTIVE: To examine the association between minority
      status and confidence to self-manage cardiovascular disease (CVD). STUDY SAMPLE:
      Survey respondents admitted to 10 hospitals participating in the "Expecting
      Success" program, with a diagnosis of CVD, during January-September 2006 (n =
      1107). RESULTS: Minority race/ethnicity was substantially associated with lower
      confidence to self-manage CVD, with 36.5% of Hispanic patients, 30.7% of Black
      patients, and 16.0% of white patients reporting low confidence (P < 0.001).
      However, in multivariate analysis controlling for socioeconomic status and
      clinical severity, minority status was not predictive of low confidence.
      CONCLUSIONS: Although there is an association between race/ethnicity and
      confidence to self-manage care, that relationship is explained by the association
      of race/ethnicity with socioeconomic status and clinical severity.

PMID- 18725847
TI  - Equity of access to outpatient care and hospitalization among older community
      residents in Brazil.
AB  - OBJECTIVE: To determine whether, as mandated by Brazilian law, health care
      (outpatient care, hospitalization) among older community residents is based on
      health-related criteria and not on other characteristics. RESEARCH DESIGN: Cross
      sectional, population-representative. SUBJECTS: Multistage, random sample of 7040
      household residents aged >or=60 years in the state of Rio Grande do Sul, Brazil.
      MEASURES: Structured in-person interviews to determine sociodemographic
      characteristics, self-reported health conditions, psychiatric status, outpatient
      service use within the previous 6 months, and number of hospitalizations within
      the previous 12 months. RESULTS: Seventy two percent reported an outpatient
      visit, 20% reported hospitalization. In controlled analyses, being female, older,
      unemployed, having private health insurance, increased the odds of an outpatient
      visit. Males, older persons, the insured, and more educated were more likely to
      report hospitalization. Race/ethnicity and religious affiliation were not
      associated with outpatient or hospital use. Pneumonia, heart disease, and urinary
      tract infection were particularly associated with both outpatient visits and
      hospitalization; diabetes, hypertension, and cancer with outpatient visit;
      stroke, cancer and psychiatric disorder with hospitalization; and heart disease,
      pneumonia, and psychiatric disorder with multiple hospitalizations. CONCLUSIONS:
      Use of health services did not differ by race/ethnicity or religion, but private
      health insurance facilitated outpatient access, and increased education
      facilitated hospitalization. Gender, age, and employment status likely reflected
      differential health needs. Improved access is needed for older persons lacking
      private health insurance, and those with little education. Patients with
      psychiatric problems merit increased attention to reduce excessive
      hospitalization.

PMID- 18725848
TI  - The association between nursing factors and patient mortality in the Veterans
      Health Administration: the view from the nursing unit level.
AB  - CONTEXT: Nurse staffing is not the same across an entire hospital. Nursing care
      is delivered in geographically-based units, with wide variation in staffing
      levels. In particular, staffing in intensive care is much richer than in
      nonintensive care acute units. OBJECTIVE: To evaluate the association of in
      hospital patient mortality with registered nurse staffing and skill mix comparing
      hospital and unit level analysis using data from the Veterans Health
      Administration (VHA). DESIGN, SETTINGS, AND PATIENTS: A retrospective
      observational study using administrative data from 129,579 patients from 453
      nursing units (171 ICU and 282 non-ICU) in 123 VHA hospitals. METHODS: We used
      hierarchical multilevel regression models to adjust for patient, unit, and
      hospital characteristics, stratifying by whether or not patients had an ICU stay
      during admission. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: : Of the
      129,579 patients, mortality was 2.9% overall: 6.7% for patients with an ICU stay
      compared with 1.6% for those without. Whether the analysis was done at the
      hospital or unit level affected findings. RN staffing was not significantly
      associated with in-hospital mortality for patients with an ICU stay (OR, 1.02;
      95% CI, 0.99-1.03). For non-ICU patients, increased RN staffing was significantly
      associated with decreased mortality risk (OR, 0.91; 95% CI, 0.86-0.96). RN
      education was not significantly associated with mortality. CONCLUSIONS: Our
      findings suggest that the association between RN staffing and skill mix and in
      hospital patient mortality depends on whether the analysis is conducted at the
      hospital or unit level. Variable staffing on non-ICU units may significantly
      contribute to in-hospital mortality risk.

PMID- 18725849
TI  - Tamoxifen for breast cancer risk reduction: impact of alternative approaches to
      quality-of-life adjustment on cost-effectiveness analysis.
AB  - BACKGROUND: In cost-effectiveness analysis (CEA), the effects of health-care
      interventions on multiple health dimensions typically require consideration of
      both quantity and quality of life. OBJECTIVES: To explore the impact of
      alternative approaches to quality-of-life adjustment using patient preferences
      (utilities) on the outcome of a CEA on use of tamoxifen for breast cancer risk
      reduction. RESEARCH DESIGN: A state transition Markov model tracked hypothetical
      cohorts of women who did or did not take 5 years of tamoxifen for breast cancer
      risk reduction. Incremental quality-adjusted effectiveness and cost-effectiveness
      ratios (ICERs) for models including and excluding a utility adjustment for
      menopausal symptoms were compared with each other and to a global utility model.
      SUBJECTS: Two hundred fifty-five women aged 50 and over with estimated 5-year
      breast cancer risk >or=1.67% participated in utility assessment interviews.
      MEASURES: Standard gamble utilities were assessed for specified tamoxifen-related
      health outcomes, current health, and for a global assessment of possible outcomes
      of tamoxifen use. RESULTS: Inclusion of a utility for menopausal symptoms in the
      outcome-specific models substantially increased the ICER; at the threshold 5-year
      breast cancer risk of 1.67%, tamoxifen was dominated. When a global utility for
      tamoxifen was used in place of outcome-specific utilities, tamoxifen was
      dominated under all circumstances. CONCLUSIONS: CEAs may be profoundly affected
      by the types of outcomes considered for quality-of-life adjustment and how these
      outcomes are grouped for utility assessment. Comparisons of ICERs across analyses
      must consider effects of different approaches to using utilities for quality-of
      life adjustment.

PMID- 18725850
TI  - The impact of symptoms and impairments on overall health in US national health
      data.
AB  - OBJECTIVE: To assess the effects on overall self-rated health of the broad range
      of symptoms and impairments that are routinely asked about in national surveys.
      DATA: We use data from adults in the nationally representative Medical
      Expenditure Panel Survey (MEPS) 2002 with validation in an independent sample
      from MEPS 2000. METHODS: Regression analysis is used to relate impairments and
      symptoms to a 100-point self-rating of general health status. The effect of each
      impairment and symptom on health-related quality of life (HRQOL) is estimated
      from regression coefficients, accounting for interactions between them. RESULTS:
      Impairments and symptoms most strongly associated with overall health include
      pain, self-care limitations, and having little or no energy. The most prevalent
      are moderate pain, severe anxiety, moderate depressive symptoms, and low energy.
      Effects are stable across different waves of MEPS, and questions cover a broader
      range of impairments and symptoms than existing health measurement instruments.
      CONCLUSIONS: This method makes use of the rich detail on impairments and symptoms
      in existing national data, quantifying their independent effects on overall
      health. Given the ongoing availability of these data and the shortcomings of
      traditional utility methods, it would be valuable to compare existing HRQOL
      measures to other methods, such as the one presented herein, for use in tracking
      population health over time.

PMID- 18725851
TI  - Survey response style and differential use of CAHPS rating scales by Hispanics.
AB  - BACKGROUND: Previous Consumer Assessments Of Healthcare Providers And Systems
      (CAHPS) studies have shown that Hispanics report care that is similar to or less
      positive than for non-Hispanic whites, yet have more positive ratings of care.
      OBJECTIVE: To examine differential use of the 0-10 rating scales in the CAHPS
      health plan survey by Hispanic ethnicity and insurance status (Medicaid vs.
      commercial managed care). DATA: CAHPS 2.0H adult Medicaid and commercial data
      submitted to the National Committee for Quality Assurance. MEASURES: The
      dependent variables are the CAHPS 2.0 ratings of care: personal doctor or nurse,
      specialists, and health care received. Ratings were categorized into 4 levels: 0
      4, 5-8, 9, and 10. The independent variable is a 4-level categorical variable:
      Hispanic Medicaid, Hispanic commercial, (non-Hispanic) white Medicaid, and (non
      Hispanic) white commercial. Six potential confounders were controlled: gender,
      age, education, self-rated health, survey mode, and survey language. ANALYSIS:
      Multinomial logistic regression was used to test for differences in extreme
      response styles. RESULTS: Hispanics exhibited a greater tendency toward extreme
      responding in the CAHPS ratings than non-Hispanic whites-in particular, they were
      more likely than whites in commercial plans to endorse a "10," and often, scores
      of 4 or less, relative to an omitted category of "5" to "8." CONCLUSIONS: The
      observed higher Hispanic ratings may be partially attributed to differences in
      response style rather than superior care. This suggests caution in the use of
      central tendency measures and the proportion of 10 ratings when examining
      racial/ethnic differences in CAHPS ratings of care. It is advisable to consider
      pooling responses at the top end (eg, 9 and 10) and lower end (eg, 0-6) of the
      response scale when making racial/ethnic comparisons.

PMID- 18725852
TI  - Adaptation of Bayesian data mining algorithms to longitudinal claims data: coxib
      safety as an example.
AB  - INTRODUCTION: Bayesian data mining methods have been used to evaluate drug safety
      signals from adverse event reporting systems and allow for evaluation of multiple
      endpoints that are not prespecified. Their adaptation for use with longitudinal
      data such as administrative claims has not been previously evaluated or
      validated. METHODS: In this pilot study, we evaluated the feasibility of adapting
      data mining methods using the empirical Bayes Multi-item Gamma Poisson Shrinkage
      (MGPS) algorithm to longitudinal administrative claims data. The Medicare Current
      Beneficiary Survey was used to identify a cohort of Medicare enrollees who were
      exposed to cyclooxygenase selective (coxib) or nonselective nonsteroidal anti
      inflammatory drugs (NS-NSAIDs) from 1999 to 2003. Empirical Bayes MGPS algorithm
      was used to simultaneously evaluate 259 outcomes associated with current use of
      coxibs versus NS-NSAIDs while adjusting for key covariates and multiple
      comparisons. For comparison, a parallel analysis used traditional epidemiologic
      methods to evaluate the relationship between coxib versus NS-NSAID use and acute
      myocardial infarction, with the goal of establishing the concurrent validity of
      the data mining approach. RESULTS: Among 9431 Medicare beneficiaries using NSAIDs
      and considering all 259 possible outcomes, empirical Bayes MGPS identified an
      association between current celecoxib use and acute myocardial infarction
      (Empirical Bayes Geometric Mean ratio 1.91) but not other outcomes. Rofecoxib use
      was associated with acute cerebrovascular events (Empirical Bayes Geometric Mean
      ratio 1.85) and several other diagnoses that likely represented indications for
      the drug. Results from the analyses using traditional epidemiologic methods were
      similar and indicated that the data mining results were valid. DISCUSSION:
      Bayesian data mining methods seem useful to evaluate drug safety using
      administrative data. Further work will be needed to extend these findings to
      different types of drug exposures and to other claims databases.

PMID- 18725853
TI  - Multilevel modeling of regional variation in equity in health care.
AB  - BACKGROUND: The use of a concentration index is recommended to estimate
      socioeconomic equity in health and health services. Methods for the analysis of
      concentration indices have been developed in several studies. However, these
      methods do not take into consideration clustering within areas, which is
      necessary in a comprehensive study of regional variations in equity. OBJECTIVES:
      The study aims to develop a statistical method to assess variations in
      socioeconomic inequities in the use of health services in relation to need in
      different regions. METHODS: Concentration index methods were developed further
      and the advantages of multilevel modeling were exploited. As an empirical example
      we analyzed revascularizations in 2001-2003 among the Finnish population.
      RESULTS: The average inequity indices for the income distribution of
      revascularizations in Finland obtained with multilevel and standard regression
      modeling were comparable, but confidence intervals were smaller with multilevel
      modeling. Inequity indices for different areas estimated using multilevel
      modeling were more conservative and had smaller confidence intervals than indices
      estimated using the standard approach. CONCLUSIONS: The proposed approach is an
      efficient way of estimating regional variations in the socioeconomic equity of
      health care use. It enables the inclusion of need in the model and takes into
      account the varying need for services in different population groups and areas.
      In addition, the advantages of using multilevel modeling to estimate indices
      include the possibility to take into account dependence between observations
      within regions and to overcome the problems associated with random error in small
      regions.

PMID- 18725854
TI  - Utilities should not be multiplied: evidence from the preference-based scores in
      the United States.
AB  - OBJECTIVE: Several estimators exist when average utility scores are not available
      for patient populations with multiple disease conditions. The multiplicative
      estimator is a widespread choice among them. Our study is to empirically test the
      accuracy of the multiplicative estimator and compare it with other estimators.
      METHODS: The Medical Expenditure Panel Survey (MEPS) has a nationally
      representative sample of the US civilian noninstitutionalized population. Using
      the pooled 2001 and 2003 data, a sample of 40,846 individuals with EQ-5D index
      scores were categorized into 238 disease condition categories. The study focus
      was the difference between the estimated and the observed mean scores for each
      comorbid pair, with the observed one presumed to be the true value. RESULTS: The
      scores estimated by multiplying the 2 mean scores of the corresponding disease
      conditions on average had a statistically significantly larger difference (P <
      0.0001) from the observed ones (-0.094) than simply picking the smaller mean of
      the 2 paired conditions (difference = 0.025), the larger mean of the 2
      (difference = 0.071), the average of the 2 means (difference = 0.048), or the
      mean of the condition with smaller sample size of the pair (difference = 0.049).
      However, the multiplicative estimator performed better than the additive
      estimator (sum of the means minus 1, difference = -0.123). CONCLUSIONS:
      Multiplication is not a good estimate when the average utility score for patients
      with 2 disease conditions is not readily available. The lower of the 2 utility
      scores had the least error among those estimators that we compared. Further
      research with an experimental design is warranted before a specific alternative
      can be firmly recommended.

PMID- 18725855
TI  - Health impact of hospital restrictions on seriously ill hospitalized patients:
      lessons from the Toronto SARS outbreak.
AB  - BACKGROUND: Restrictions on non-urgent hospital care imposed to control the 2003
      Toronto severe acute respiratory syndrome outbreak led to substantial disruptions
      in hospital clinical practice, admission, and transfer patterns. OBJECTIVES: We
      assessed whether there were unintended health consequences to seriously ill
      hospitalized patients. STUDY DESIGN, SETTING, AND POPULATION: Population-based
      longitudinal cohort study of patients residing in Toronto or an urban control
      region with an incident admission for 1 of 7 serious conditions in the 3 years
      before, or the 4 months during or after restrictions. OUTCOME MEASURES: Short
      term mortality, overall readmissions, cardiac readmissions for acute myocardial
      infarction patients, serious complications for very low birth weight babies, and
      quality of care measures, comparing adjusted rates across time periods within
      regions. RESULTS: Mortality, readmission, and complication rates did not change
      for any condition during or after severe acute respiratory syndrome restrictions.
      Although rates of invasive cardiac procedures for acute myocardial infarction
      patients decreased 11-37% in Toronto, rates of nonfatal cardiac outcomes did not
      change. CONCLUSIONS: Restrictions on non-urgent hospital utilization and hospital
      transfers may be a safe public health strategy to employ to control nosocomial
      outbreaks or provide hospital surge capacity for up to several months, in large,
      well-developed healthcare systems with good availability of community-based care.

PMID- 18725856
TI  - How many walked through the door?: the effect of hurricane Katrina evacuees on
      Houston emergency departments.
AB  - BACKGROUND: Hurricane Katrina necessitated the evacuation of over 200,000 New
      Orleans residents into Houston in the days after landfall. The already stressed
      emergency departments (EDs) were faced with a potential influx of patients
      suffering injuries and conditions exacerbated by the hurricane and resulting
      devastation. OBJECTIVE: To examine the effect of Katrina evacuees on Houston EDs
      after the hurricane. DESIGN: Data from visits to 25 Houston EDs in 2005 (n =
      875,750) were analyzed to evaluate the impact of visits by Katrina evacuees (n =
      8427). MEASURES: Descriptive counts of ED visits by individuals with a FEMA
      designated disaster area zip code due to Katrina. RESULTS: In September,
      immediately after Katrina, Houston-area EDs reported the lowest monthly total
      visits in 2005 despite treating 4518 evacuees that month. On aggregate, the
      increase in visits by evacuees did not overwhelm area EDs, as they coincided with
      a decrease in ED utilization by nonevacuees and over 20,000 evacuees were seen at
      medical clinics in the large shelters. The highest number of evacuee visits to an
      individual ED was 86, on September 1. The peak day of visits, totaling 364,
      occurred on September 3. The ED that bore 15% of total visits saw no more than 19
      evacuees daily. Evacuee and nonevacuee visits dropped dramatically when hurricane
      Rita threatened Houston. CONCLUSIONS: Houston EDs experienced an increase in
      visits by Katrina evacuees in the hurricane's aftermath. However, the initial
      surge of visits was modest and corresponded with decreases in visits by
      nonevacuees and medical care provided in large shelters.

PMID- 18725857
TI  - Decreasing use of controlled-release oxycodone: response to Morden et al, June
      2008 Medical Care.

PMID- 18725859
TI  - Cost-effectiveness of hearing aids in the hearing-impaired elderly: a
      probabilistic approach.
AB  - OBJECTIVE: Hearing aids are the principal tool for rehabilitation of hearing
      loss, one of the most prevalent impairments among elderly adults, but cost
      utility ratings for hearing aid use are limited. DESIGN: Cost-effectiveness
      analysis. SETTING AND PATIENTS: A multistate Markov model was constructed to
      model 50- to 80-year-old patients moving between states, including normal
      hearing, mild, moderate, or severe hearing loss. Parameters assigned in the model
      are partly derived from the Medline source (1966-2005) and partly from data on
      hearing-impaired elders (n = 96) in a tertiary care center in Taiwan. To address
      uncertainty, most of the parameters were specified by distributions, rather than
      base-case values. A probabilistic approach with Monte Carlo simulations was
      performed to produce an acceptability curve, showing the probabilities of being
      cost-effective given threshold values of willingness to pay (WTP). MAIN OUTCOME
      MEASURES: Hearing-related quality-adjusted life-years and cost in US dollars and
      Euros. RESULTS: The incremental costs for gaining an additional hearing-related
      quality-adjusted life-years in women and men were US $13,615 (Euro 10,826) and
      9,702 (Euro 7,715), respectively. The probability of being cost-effective
      increased to 53% in women and 65% in men given a WTP of US $12,000 (Euro 9,542).
      The probabilities of being cost-effective to reach plateau were 67% for women and
      78% for men given a WTP of US $20,000 (Euro 15,904). CONCLUSION: By modeling
      different degrees of hearing loss with a multistate model, hearing aid use was
      demonstrated to be a cost-effective strategy to rehabilitate the hearing-impaired
      elderly. These results can assist policy makers in allocating health resources
      appropriately and effectively.

PMID- 18725858
TI  - Quality of life in patients with idiopathic sudden hearing loss: comparison of
      different therapies using the Medical Outcome Short Form (36) Health Survey
      questionnaire.
AB  - BACKGROUND: Cause and underlying pathogenic mechanisms of idiopathic sudden
      hearing loss (ISHL) are not fully understood, resulting in the widespread use of
      different polypragmatic treatment approaches, which have not been finally
      validated in randomized controlled trials. Quality of life (QoL) can provide
      helpful additional information when selecting the most appropriate therapy within
      current options. METHODS: In a prospective, multicenter, randomized, controlled
      clinical study, Rheopheresis-a method of therapeutic apheresis-was compared with
      a standard therapy consisting of either intravenous corticosteroids or
      hemodilution using pure-tone and speech audiometry. Quality of life as secondary
      outcome parameter was documented using the German Medical Outcome Short Form (36)
      Health Survey questionnaire. RESULTS: Two hundred forty patients were included in
      this trial. All three treatment options proved to be of equal efficacy regarding
      absolute and relative hearing gain or speech discrimination. Quality of life
      measured in Medical Outcome Short Form (36) Health Survey scores was less than
      the level of the normal German population at baseline for all groups, and
      mentally, ISHL patients felt more impaired than patients who have chronic hearing
      impairment. Rheopheresis treatment led to a higher QoL at the time of the follow
      up visit compared with the drug-based therapies and compared with a large
      representative sample of the German general population. DISCUSSION: Treatments
      leading to accelerated recovery in combination with a minimal number of
      therapeutic interventions, for example, Rheopheresis, seemed to have a
      considerable effect on QoL. Because there is a dearth of evidence of efficacy for
      any treatment option in ISHL, QoL can provide additional information when
      choosing the most appropriate treatment option.

PMID- 18725860
TI  - Autologous serum eardrops therapy with a chitin membrane for closing tympanic
      membrane perforations.
AB  - OBJECTIVE: Office treatment for chronic tympanic membrane (TM) perforations has
      limitations, and alternative methods to myringoplasty are sometimes needed. Serum
      lacks antigenicity and contains a large variety of growth factors known to
      modulate proliferation of various tissues to promote wound healing effects. Our
      purpose was to evaluate the feasibility of autologous serum eardrops therapy with
      a chitin membrane for closing TM perforations. INTERVENTION: In the outpatient
      clinic, the perforation margin was cauterized with silver nitrate, and the
      perforation was covered with a chitin membrane. Patients were instructed to apply
      autologous serum eardrops daily. Patients were examined every 2 weeks, and the
      procedure was repeated. RESULTS: We treated 19 sequential patients with chronic
      TM perforation in 1 ear between October 2005 and September 2007. Closure of the
      TM was achieved in 11 (58%) of 19 ears, and reduction of the perforation size was
      observed in 2 ears (11%). Closure rates for small, medium, and large perforations
      were 57 (8 of 14), 0 (0 of 1), and 75% (3 of 4), respectively. Closure rates for
      perforations attributable to intratympanic dexamethasone treatment, after
      myringoplasty and chronic otitis media were 67 (2 of 3), 67 (2 of 3), and 54% (7
      of 13), respectively. Time for closure took from 15 to 175 days, with an average
      of 68 days (5.9 clinic visits). During autologous serum eardrop therapy with a
      chitin membrane, no remarkable side effects in the treated ears were observed.
      Measurement of the concentration of the epidermal growth factor, transforming
      growth factor beta1, fibronectin, and interleukin 6 in the serum showed no
      decrease in 14 days, suggesting activity remained stable in that period.
      CONCLUSION: Autologous serum eardrops therapy with a chitin membrane, which
      requires no surgical intervention, was found to be a promising office-based
      technique for the closure of chronic TM perforations because of its ease,
      safeness, and feasibility. However, additional studies are needed to
      independently analyze the specific benefits of the serum drops and the chitin
      membrane.

PMID- 18725861
TI  - Regional myo-inositol concentration in mild cognitive impairment Using 1H
      magnetic resonance spectroscopic imaging.
AB  - The goal was to assess regional patterns of metabolite abnormalities in mild
      cognitive impairment (MCI) and Alzheimer disease (AD) patients using proton
      magnetic resonance spectroscopy imaging at 1.5 Tesla. Fourteen MCI, 17 AD, and 16
      healthy control (HC) subjects were studied. MCI was associated with higher myo
      inositol (mIn) concentration in right parietal white matter compared with HC and
      lower mIn levels in frontal white matter compared with AD. AD was associated with
      higher mIn concentration in frontal and parietal white matter compared with HC. N
      acetylaspartate (NAA) concentration of white matter was similar in all groups,
      whereas NAA concentration of gray matter showed a trend toward lower values in
      the right parietal lobe in AD compared with MCI and HC. A mIn increase in white
      matter in absence of significant NAA reduction suggests that mIn is a more robust
      and sensitive marker of white matter pathology in AD and MCI than NAA.
      Furthermore, the dissociation between mIn and NAA alterations in white matter
      could provide important information regarding the role of glial and neuronal
      damage in MCI and AD.

PMID- 18725862
TI  - Older Americans' risk-benefit preferences for modifying the course of Alzheimer
      disease.
AB  - Alzheimer disease (AD) is a progressive, ultimately fatal neurodegenerative
      illness affecting millions of patients, families, and caregivers. Effective
      disease-modifying therapies for AD are desperately needed, but none currently
      exist on the market. Thus, accelerating the discovery, development, and approval
      of new disease-modifying drugs for AD is a high priority for individuals,
      physicians, and medical decision makers. Potentially disease-modifying drugs
      likely will have significant therapeutic benefits but also may have treatment
      related risks. We quantified older Americans' treatment-related risk tolerance by
      eliciting their willingness to accept the risk of treatment-related death or
      permanent severe disability in exchange for modifying the course of AD. A stated
      choice survey instrument was administered to 2146 American residents 60 years of
      age and older. On average, subjects were willing to accept a 1-year risk of
      treatment-related death or permanent severe disability from stroke of over 30%
      for a treatment that prevents AD from progressing beyond the mild stage. Thus,
      most people in this age cohort are willing to accept considerable risks in return
      for disease-modifying benefits of new AD drugs. These results are consistent with
      other studies indicating that individuals view AD as a serious, life threatening
      illness that imposes heavy burdens on both patients and caregivers.

PMID- 18725863
TI  - Global and temporal cortical folding in patients with early-onset schizophrenia.
AB  - OBJECTIVE: Adult-onset schizophrenia has repeatedly been associated with
      disturbances in the temporal lobes and alterations in cortical folding, which are
      thought to reflect neurodevelopmental impairment. Early-onset schizophrenia (EOS;
      onset before 18 years) is considered to involve even more pronounced
      neurodevelopmental deviance across a wide range of brain structural measures. We
      hypothesized that overall alteration of cortical folding also applies to EOS, and
      EOS involves prominent structural aberrations in superior temporal and collateral
      sulci. METHOD: Magnetic resonance T1 images of 51 patients with EOS and 59
      healthy participants were investigated. A fully automated method was applied to
      the images to extract, label, and measure the sulcus area in the whole cortex.
      Cortical folding was assessed by computing global sulcal indices (the ratio
      between total sulcal area and total outer cortex area) for each hemisphere and
      local sulcal indices (the ratio between the area of labeled sulcus and total
      outer cortex area in the corresponding hemisphere) for superior temporal and
      collateral sulci. RESULTS: Relative to healthy individuals, patients with EOS had
      significantly lower global sulcal indices in both hemispheres and a lower local
      sulcal index in the left collateral sulcus. CONCLUSIONS: Reduced hemispheric
      sulcation appears to be a feature of schizophrenia, irrespective of age at onset.
      Structural aberration involving the left collateral sulcus may contribute to
      neurobiological substrate of EOS.

PMID- 18725864
TI  - Is the menopausal transition stressful? Observations of perceived stress from the
      Seattle Midlife Women's Health Study.
AB  - OBJECTIVE: To describe changes in the levels of perceived stress in relation to
      menopausal transition (MT)-related factors (MT stage, hot flash severity, urinary
      estrone glucuronide, urinary follicle-stimulating hormone, hormone therapy),
      aging and age-related changes, and psychosocial factors (income adequacy, role
      burden, social support, parenting, employment, history of sexual abuse, depressed
      mood). DESIGN: A subset of participants (N = 418) in the longitudinal Seattle
      Midlife Women's Health Study provided data during the late reproductive and early
      and late MT stages or early postmenopause (PM) from 1990 to 2005, including
      menstrual calendars for staging the MT, annual health reports, and first morning
      urine specimens (assayed for estrone and follicle-stimulating hormone).
      Multilevel modeling was used to test patterns of perceived stress related to MT
      related and aging-related factors and psychosocial factors with as many as 1,814
      observations from 418 women per factor. Age was centered at 47.9 years. RESULTS:
      The effects of the MT-related factors were not significant, although the stress
      ratings decreased during PM by 0.11 units (P = 0.06). In analyses with age as a
      covariate and with each covariate added separately, employment was associated
      with significantly higher levels of stress (beta = 0.14, P < 0.0001), as was
      history of sexual abuse (beta = 0.11, P = 0.03) and depressed mood (beta = 0.02,
      P < 0.0001). Improvement in each of the factors of role burden, social support,
      and income adequacy was associated with significantly lower perceived stress
      (beta = -0.19, -0.13, and -0.10, respectively; P < 0.0001 for all). Negative
      appraisal of aging changes and perceived poorer health were both associated with
      significantly higher stress levels (beta = 0.08, P < 0.0001 for both) and
      depressed mood (beta = -0.02, P < 0.0001). A multivariate model included
      significant effects of employment, perceived health, and depressed mood (beta =
      0.24, -0.04, and 0.02, respectively; P < 0.0001 for all). CONCLUSIONS: Being
      employed, experiencing depressed mood, and perceiving one's health as poor were
      more important in women's evaluation of their daily stress than severity of hot
      flashes, MT-related factors, or other social factors. Clinicians working with
      women going through the MT should remain vigilant to the impact of social
      circumstances of women's lives, especially employment, as well as focusing on the
      psychosocial and endocrine features of this transition.

PMID- 18725865
TI  - Newer antidepressants for hot flashes--should their efficacy still be up for
      debate?
AB  - OBJECTIVE: Newer antidepressants have been shown in clinical trials to reduce hot
      flashes, although not as well as do hormones. Nonetheless, a recently published
      meta-analysis and subsequent editorial raised doubts with regard to the utility
      of newer antidepressants for treating hot flashes. Concerns about the lack of
      efficacy of newer antidepressants on hot flashes were based in large part on
      results of two placebo-controlled, double-blind trials, one evaluating
      venlafaxine and the other individually evaluating both fluoxetine and citalopram.
      These two studies have repeatedly been put forward as evidence that newer
      antidepressants are not definitively proven to reduce hot flashes. DESIGN: Raw
      data from these two randomized, placebo-controlled trials evaluating second
      generation antidepressants for hot flashes were obtained. These data and
      subsequent study conclusions are evaluated and discussed in the context of other
      published trial data regarding the use of newer antidepressants for treating hot
      flashes. RESULTS: Examination of the raw data from these two trials revealed that
      neither employed a baseline period of hot flash determination against which to
      calculate changes over time from baseline. CONCLUSIONS: Recognition that these
      two trials cannot be used to look at hot flash frequency or score changes from
      baseline limits their ability to inform the efficacy literature about the use of
      newer antidepressants for hot flash reduction.

PMID- 18725866
TI  - Changes in skin topography during hormone therapy.
AB  - The influence of female sex hormones on skin aging has repeatedly been
      investigated with contradictory results. In our study, the skin roughness of
      eight women receiving hormone therapy decreased significantly by approximately
      15% in 12 months. Our results provide new evidence of the antiaging effect of
      female sex hormones.

PMID- 18725867
TI  - Serotonin (5-hydroxytryptamine) transporter inhibition causes bone loss in adult
      mice independently of estrogen deficiency.
AB  - OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) treat depression by
      antagonizing the serotonin (5-hydroxytryptamine) transporter (5-HTT). These drugs
      may also have skeletal effects given the presence of functional serotonergic
      pathways in bone and evidence demonstrating detrimental effects of SSRIs on
      postmenopausal bone changes. This study aimed to explore the influence of an SSRI
      (fluoxetine hydrochloride) on the bone changes associated with estrogen
      deficiency in adult mice. DESIGN: Adult, female, Swiss-Webster mice underwent
      ovariectomy (OVX) or sham OVX and were treated daily for 4 weeks with either
      fluoxetine hydrochloride (5 or 20 mg/kg) or a vehicle solution (control). In vivo
      assessments of hindlimb areal and tibial volumetric bone mineral density were
      performed at baseline and after 4 weeks of intervention. Femurs and lumbar
      vertebrae were subsequently removed and assessed ex vivo for bone mineral density
      and trabecular bone architecture and turnover. RESULTS: In vivo and ex vivo
      skeletal measures found no interactions between OVX (estrogen deficiency) and 5
      HTT inhibition, indicating that the skeletal effects of these interventions were
      independent. 5-HTT inhibition had detrimental skeletal effects, with the
      fluoxetine-treated groups having reduced bone mineral density and altered
      trabecular architecture. These changes resulted from both a decrease in bone
      formation and increase in bone resorption. CONCLUSIONS: These data indicate that
      a commonly prescribed SSRI has a negative influence on the adult skeleton,
      independent of estrogen deficiency. This finding supports clinical data
      demonstrating SSRI use to be associated with accelerated bone loss after
      menopause and highlights a need for further research into the skeletal effects of
      SSRIs.

PMID- 18725868
TI  - Prescription opioid dependence is associated with poorer outcomes in disabling
      spinal disorders.
AB  - STUDY DESIGN: Prospective outcomes study involving patients with chronic
      disabling occupational spinal disorders (CDOSD) diagnosed with (n = 199) or
      without (n = 1124) postinjury opioid-dependence disorder (ODD), based on the
      Diagnostic and Statistical Manual of Mental Disorders-fourth edition cirteria.
      OBJECTIVE: To determine whether prescription opioid dependence, assessed at the
      beginning of rehabilitation treatment, is associated with poorer treatment
      outcomes in patients with CDOSDs attending an interdisciplinary rehabilitation
      program. SUMMARY OF BACKGROUND DATA: Controversy exists regarding the risk of
      iatrogenic ODD and treatment outcomes when long-term opioid therapy is used in
      the treatment of chronic nonmalignant pain conditions. METHODS: A consecutive
      sample of patients with CDOSDs [n = 1323; mean (SD) length of disability = 18.8
      (20.7) months] attending a tertiary referral center received intensive physical
      reactivation and pain/disability management interventions, based on a functional
      restoration model, including detoxification from opioids. One-year outcomes
      included return to work, work retention, healthcare utilization, new surgeries,
      recurrent injuries, and disability claim settlement. RESULTS: Prevalence of ODD
      in this CDOSD population on entering the rehabilitation program was 15%. Even
      after adjusting for relevant demographic factors and comorbid psychiatric
      disorders, opioid-dependent patients were 1.7 times [95% confidence interval
      (CI): 1.0, 2.7] less likely to return to work, 2 times (95% CI: 1.3, 3.0) less
      likely to retain work at the 1-year interview, and 1.7 times (95% CI: 1.2, 2.5)
      more likely to engage in healthcare utilization from new providers, compared with
      nonopioid-dependent patients. CONCLUSIONS: Iatrogenic prescription opioid
      dependence may be a risk factor for less successful long-term work and health
      outcomes, even after detoxification from opioids as part of an interdisciplinary
      functional rehabilitation program. Chronic prescription opioid dependence in this
      patient population is also associated with a significantly higher prevalence of
      comorbid psychiatric conditions, both axis I and II.

PMID- 18725869
TI  - Bone morphogenetic protein (RhBMP-2) as a substitute for iliac crest bone graft
      in multilevel adult spinal deformity surgery: minimum two-year evaluation of
      fusion.
AB  - STUDY DESIGN: Prospective, single center, nonblinded radiographic analysis of
      anterior and posterior adult spinal deformity fusions performed with bone
      morphogenetic protein (rhBMP-2). OBJECTIVE: To determine the ability of rhBMP-2
      to achieve multilevel spinal fusion in the deformity patient. SUMMARY OF
      BACKGROUND DATA: No previous study has evaluated rhBMP-2 for multilevel adult
      spinal deformity fusion with 2-year results. We postulated fusion could be
      achieved without distant autogenous graft harvest. METHODS: Prospective analysis
      was performed for 98 patients (308 levels; mean age, 51.4 years) who underwent
      multilevel anterior or posterior spinal fusion (PSF) with minimum 2-year follow
      up (average, 2.6 years). Group 1 (10 mg/level) contained 47 patients (109 levels;
      2.33 levels/patient) who underwent anterior spinal fusion (ASF): BMP on an
      absorbable collagen sponge (ACS) with a titanium mesh cage. Group 2 (20 mg/level)
      included 43 patients (156 levels; 3.63 levels/patient) with PSF: BMP on an ACS
      with local bone graft (LBG) and bulking agent [tricalcium
      phosphate/hydroxyapatite (TCP-HA)]. Group 3 (40 mg/level) contained 8 patients
      (43 levels; 5.38 levels/patient) with PSF: rhBMP-2 and TCP-HA with no autologous
      bone. Confounding negative factors were present in the study population: medical
      comorbidities (26%), tobacco use (17%), revision surgery (34%), previous
      laminectomy (51%), and preoperative pseudarthrosis (27%). Postoperative films
      (AP, lateral, oblique) were evaluated by independent observers. Average fusion
      grade was based on a published scale. RESULTS: Overall fusion rate was 95%.
      (group 1 91%, group 2 97%, group 3 100%). No confounding factor demonstrated a
      detrimental statistical significance to fusion. CONCLUSION: In multilevel ASF,
      BMP (10 mg/level) generates fusion without autogenous bone. In multilevel PSF,
      BMP (20 mg/level) with LBG and TCP-HA produced fusion. BMP (40 mg/level) and TCP
      HA without LBG achieved fusion. In multilevel spinal fusion, rhBMP-2 eliminated
      the necessity for iliac crest bone graft and yielded an excellent fusion rate.

PMID- 18725870
TI  - Point of view.

PMID- 18725871
TI  - Is research presented at the scoliosis research society annual meeting influenced
      by industry funding?
AB  - STUDY DESIGN: All abstracts submitted to the 2006 SRS annual meeting were
      reviewed. OBJECTIVE: To determine the rate of funding in abstracts submitted for
      presentation at the 2006 Annual Scoliosis Research Society (SRS) meeting and
      whether funding produced bias toward a positive outcome. SUMMARY OF BACKGROUND
      DATA: Financial conflicts of interest have been attributed to bias in research.
      METHODS: Three members the SRS Program Committee reviewed 610 abstracts submitted
      for presentation at the 2006 annual meeting. The committee's average grade was
      correlated with type of funding (industry, professional society, university);
      abstract conclusions (favorable, unfavorable, or only descriptive); and subject
      category [adolescent idiopathic scoliosis (AIS), motion preservation, etc.].
      RESULTS: Of the 610 submitted articles, 72% (n = 440) were unfunded. Of the 170
      funded articles, 140 were supported by industry, 7 by government agency, 8 by
      professional societies, 4 by universities, and 11 by private foundations. There
      was no statistically significant difference between the reviewers' grades of
      funded versus unfunded articles (P = 0.39). Comparing AIS articles to all the
      other categories, the number of funded articles were significantly greater only
      in motion preservation (P < 0.001) and genetics (P = 0.039). When a
      consultant/employee relationship was present, there was a significant difference
      in the proportion of funded articles and favorable findings (P = 0.048).
      CONCLUSION: The higher percentage of funded articles in motion preservation and
      genetics compared to AIS articles could reflect a bias in those 2 areas. However,
      although there were more funded articles in those 2 areas there were not more
      funded, favorable articles (motion preservation P = 0.059, and genetics P = 0.3).
      Thus, certain categories attracted more funding than others but there was not a
      bias toward favorable findings within the funded articles unless the funding was
      due to a consultant/employee relationship.

PMID- 18725873
TI  - Sleeping beauty vector system moves toward human trials in the United States.

PMID- 18725876
TI  - The clone ranger?

PMID- 18725877
TI  - Fighting fire with fire: effects of oncolytic virotherapy on underlying viral
      hepatitis in hepatocellular carcinoma.

PMID- 18725878
TI  - Peptide-conjugated antisense therapy takes a skip ahead.

PMID- 18725879
TI  - Resistant hypertension: a clinical syndrome in search of a definition.

PMID- 18725880
TI  - Unraveling the genetic predisposition for aortic aneurysms: is it time for
      tailored medicine?

PMID- 18725881
TI  - Determinants of nondipping in nocturnal blood pressure and specific
      nonpharmacological treatments for nocturnal hypertension.

PMID- 18725884
TI  - ERAAP prevents leader dominance?

PMID- 18725885
TI  - Characterizing the glycome of the mammalian immune system.
AB  - The outermost layer of all immune cells, the glycocalyx, is composed of a complex
      mixture of glycoproteins, glycolipids and lectins, which specifically recognize
      particular glycan epitopes. As the glycocalyx is the cell's primary interface
      with the external environment many biologically significant events can be
      attributed to glycan recognition. For this reason the rapidly expanding glycomics
      field is being increasingly recognized as an important component in our quest to
      better understand the functioning of the immune system. In this review, we
      highlight the current status of immune cell glycomics, with particular attention
      being paid to T- and B-lymphocytes and dendritic cells. We also describe the
      strategies and methodologies used to define immune cell glycomes.

PMID- 18725886
TI  - International bowel function extended spinal cord injury data set.
AB  - STUDY DESIGN: International expert working group. OBJECTIVE: To develop an
      International Bowel Function Extended Spinal Cord Injury (SCI) Data Set
      presenting a standardized format for the collection and reporting of an extended
      amount of information on bowel function. SETTING: Working group consisting of
      members appointed by the American Spinal Injury Association (ASIA) and the
      International Spinal Cord Society (ISCoS). METHODS: A draft prepared by the
      working group was reviewed by Executive Committee of the International SCI
      Standards and Data Sets and later by the ISCoS Scientific Committee and the ASIA
      Board. Relevant and interested scientific and professional organizations and
      societies (around 40) were also invited to review the data set and it was posted
      on the ISCoS and ASIA websites for 3 months to allow comments and suggestions.
      The ISCoS Scientific Committee, ISCoS Council and ASIA Board received the data
      set for final review and approval. RESULTS: The International Bowel Function
      Basic SCI Data Set includes 26 items providing a thorough description of bowel
      related symptoms as well as clinical assessment of anal sphincter function and
      description of total gastrointestinal or segmental colorectal transit times.
      CONCLUSION: An International Bowel Function Extended SCI Data Set has been
      developed. This Data Set is mainly for research purposes and it should be used in
      combination with the information obtained from the International SCI Core Data
      Set and the International Bowel Function Basic SCI Data Set.

PMID- 18725887
TI  - International bowel function basic spinal cord injury data set.
AB  - STUDY DESIGN: International expert working group. OBJECTIVE: To develop an
      International Bowel Function Basic Spinal Cord Injury (SCI) Data Set presenting a
      standardized format for the collection and reporting of a minimal amount of
      information on bowel function in daily practice or in research. SETTING: Working
      group consisting of members appointed by the American Spinal Injury Association
      (ASIA) and the International Spinal Cord Society (ISCoS). METHODS: A draft
      prepared by the working group was reviewed by Executive Committee of the
      International SCI Standards and Data Sets, and later by ISCoS Scientific
      Committee and the ASIA Board. Relevant and interested scientific and professional
      (international) organizations and societies (approximately 40) were also invited
      to review the data set and it was posted on the ISCoS and ASIA websites for 3
      months to allow comments and suggestions. The ISCoS Scientific Committee, Council
      and ASIA Board received the data set for final review and approval. RESULTS: The
      International Bowel Function Basic SCI Data Set includes the following 12 items:
      date of data collection, gastrointestinal or anal sphincter dysfunction unrelated
      to SCI, surgical procedures on the gastrointestinal tract, awareness of the need
      to defecate, defecation method and bowel care procedures, average time required
      for defecation, frequency of defecation, frequency of fecal incontinence, need to
      wear pad or plug, medication affecting bowel function/constipating agents, oral
      laxatives and perianal problems. CONCLUSION: An International Bowel Function
      Basic SCI Data Set has been developed.

PMID- 18725888
TI  - Reticular formation and spinal cord injury.
AB  - STUDY DESIGN: Compact literature review to provide basic knowledge of the
      reticular formation (RF) for clinicians. SETTING: United Kingdom. MATERIALS AND
      METHODS: The anatomical findings were collected from very recently published and
      well-edited books on neuroscience instead of hundreds of articles that contain
      materials still requiring test of time and difficult for busy clinicians to
      digest. Other individual references on specific issues such as a micturition
      centre, source of sildenafil citrate and so on are added. Clinical considerations
      discuss commonly encountered problems of spinal cord injury service and science.
      Every clinical condition is discussed in conjunction with the anatomy and
      physiology of the RF. RESULTS: This section involves anatomy. (1) The core RF is
      located in the brain stem. The RF proper is divided into three longitudinal
      zones: the lateral (sensory), the medial (motor) and the midline (all others)
      zone. The midline zone is essential for wakefulness and consciousness. (2) Other
      brain stem structures sharing functions of the RF proper: periaqueductal grey
      (PAG), red nuclei, inferior olivary nucleus and precerebellar nucleus. PAG is
      almost related to all functions of the central nervous system, whereas the others
      are more connected to cerebellar functions of movements. (3) Spinal cord RF is
      located in the intermediolateral zone. It sends ascending and receives descending
      signals to coordinate and modulate motor, sensory and other functions.
      DISCUSSION: This section involves clinical consideration. Multisystem damage,
      muscle contraction, upper urinary tract, sexual behaviour, skin trophic, pain,
      sleep apnoea, cross-system damages, spinal cord repair and comprehensive
      management are discussed to enlighten the clinical importance of the RF.

PMID- 18725889
TI  - The effectiveness of physical interventions for people with spinal cord injuries:
      a systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVES: To provide a quantitative analysis
      of all randomized controlled trials designed to determine the effectiveness of
      physical interventions for people with spinal cord injury (SCI). SETTING: Sydney,
      Australia. METHODS: A search was conducted for randomized controlled trials
      involving physical interventions for people with SCI. Two reviewers independently
      rated methodological quality using the PEDro scale and extracted key findings
      from the trials. RESULTS: Four thousand five hundred and forty three abstracts
      were identified of which 31 trials met the inclusion criteria. Trials examined
      the effectiveness of fitness and strength training (n=7), gait training (n=5),
      hand therapy (n=3), stretch (n=4), acupuncture (n=3), hand splinting (n=2) and
      other related therapies (n=7). Six trials reported a between-group mean
      difference with a clearly important treatment effect on at least one outcome
      measure. These trials supported the use of fitness, strength and gait training as
      well as acupuncture. CONCLUSION: There is initial evidence supporting the
      effectiveness of some physical interventions for people with SCI. However, there
      is a pressing need for high-quality trials to determine the effectiveness of all
      physical interventions commonly administered in clinical practice.

PMID- 18725890
TI  - Differential modulation of diet-induced obesity and adipocyte functionality by
      human apolipoprotein E3 and E4 in mice.
AB  - OBJECTIVE: Apolipoprotein E (apoE), a key protein in lipid metabolism, is highly
      expressed in adipose tissues. Studies have shown that human APOE*4 is associated
      with a lower body mass index but with a greater risk of coronary heart disease
      compared with other APOE alleles. To define the isoform-specific role of apoE in
      regulating the expandability and functionality of adipose tissues, we
      investigated the effects of diet-induced obesity in mice whose endogenous Apoe
      gene has been replaced by either the human APOE*3 or APOE*4 allele. RESULTS:
      After 8 weeks on a Western-type high-fat diet, male APOE4 mice displayed impaired
      tolerance to glucose and fat overload compared with APOE3 mice. Subcutaneous fat
      tissues in APOE4 and APOE3 mice after high fat feeding were not different. In
      contrast, although epididymal fat tissues in APOE4 mice gained 30% less weight
      during the high fat feeding than in APOE3 mice, they showed impaired insulin
      stimulated glucose uptake ex vivo. Epididymal APOE4 adipocytes were larger in
      size than APOE3 adipocytes, and expressed reduced levels of mRNA for peroxisome
      proliferator-activated receptor gamma2 and adiponectin, important markers of
      adipocyte functionality. Adenoviral expression of apoE3 in apoE-null culture
      adipocytes induced adiponectin mRNA in a dose-dependent manner, but the induction
      was significantly blunted in cells overexpressing apoE4. However, in contrast to
      the apoE3-expressing cells, Glut1, but not Glut4, expression levels were
      positively correlated with increased apoE4 mRNA, suggesting that apoE4 expression
      in adipocyte interferes in insulin-sensing pathways. CONCLUSION: Dysfunctional
      epididymal adipose tissues contribute to the accelerated impairment of glucose
      tolerance in APOE4 mice fed a Western-type diet. Our results underscore the
      importance of functionality of individual fat depots rather than total fat mass
      as a determinant for metabolic disturbance during diet-induced obesity.

PMID- 18725891
TI  - Metabolic and behavioral responses to high-fat feeding in mice selectively bred
      for high wheel-running activity.
AB  - OBJECTIVE: Increased dietary fat intake is a precipitating factor for the
      development of obesity and associated metabolic disturbances. Physically active
      individuals generally have a reduced risk of developing these unhealthy states,
      but the underlying mechanisms are poorly understood. In the present study, we
      investigated the effects of feeding a high-fat diet (HFD) on obesity development
      and fuel homeostasis in male and female mice with a trait for increased physical
      activity and in their controls. METHODS: Male and female mice selectively bred
      for a high level of wheel running behavior over 30 generations and nonselected
      controls (background strain Hsd:ICR) were maintained on a standard lab chow high
      carbohydrate diet (HCD) or on an HFD (60% fat). Food intake, body weight,
      indirect calorimetry parameters, spontaneous locomotor activity and several
      hormones relevant to metabolism and energy balance were measured. RESULTS: On
      HFD, mice reduced food intake and increased body fat mass and plasma leptin
      levels, with the notable exception of the selected females, which increased their
      ingested calories without any effects on body mass or plasma leptin levels. In
      addition, they had an elevated daily energy expenditure (DEE), increased
      spontaneous cage activity ( approximately 700% relative to controls) and higher
      resting metabolic rate (RMR) on the HFD compared with feeding the HCD. The
      selected males also had a higher DEE compared with controls, but no interaction
      with diet was observed. On HCD, adiponectin levels were higher in selected male,
      but not female, mice relative to controls. A marked increase in the level of
      plasma adiponectin was observed on the HFD in selected females, an effect of diet
      that was not observed in selected males. CONCLUSION: Genetically based high
      locomotor activity renders female, but not male, mice resistant to HFD-induced
      obesity by alterations in behavioral, endocrine and metabolic traits that
      facilitate fat utilization rather than limiting HFD intake.

PMID- 18725892
TI  - Obesity enhances gastrointestinal tumorigenesis in Apc-mutant mice.
AB  - Epidemiological evidence indicates a link between obesity and human colon cancer.
      A putative association between obesity and colon tumorigenesis has been explored
      experimentally using chemical carcinogens administered to obese rodents. The main
      objective of this study was to generate a new mouse line that displays both
      obesity and intestinal tumorigenesis. To this end, we have generated C57BLKS
      mLepr(db/db); Apc(1638N/+) mice combining both db and Apc mutations. The db
      mutation results in obesity and type 2 diabetes, the Apc mutation is a key
      initiating event of intestinal neoplasia. All mice were euthanized at 6 months of
      age and all regions of the gastrointestinal tract examined for tumors. The
      results show that the combination of Apc(1638N/+) and db mutations not only
      enhanced mutant Apc-driven small intestinal tumorigenesis but also induced
      gastric and colonic tumors. Homozygous db mice did not develop gastrointestinal
      neoplasia. These findings indicate that obesity associated with type 2 diabetes
      promotes gastrointestinal tumorigenesis in Apc-deficient mice and provides
      evidence of a mechanistic link between obesity and colorectal neoplasia.

PMID- 18725893
TI  - The mitigating influence of time preference on the relation between smoking and
      BMI scores.
AB  - OBJECTIVE: Prior studies have found a strong negative relation between smoking
      and body mass index (BMI). Smoking and unhealthy eating both imply a preference
      for utility in the present at the expense of future consumption. This analysis
      seeks to proxy this preference through a composite index of equally weighted
      intertemporal behaviors to isolate the impact of smoking upon BMI independent of
      time discounting. DESIGN: Ordinary least squares regression is used to analyze
      BMI score based on a number of key independent variables. SUBJECTS: A total of
      2970 individuals who provided data for the United States Department of
      Agriculture's (USDA) Continuing Survey of Food Intakes by Individuals (CSFII)
      1994-1996, as well as the Diet and Health Knowledge Survey (DHKS). RESULTS:
      Adding time preference to a multivariate model inflates the magnitude of the
      smoking effect, consistent with discounted utility theory. CONCLUSIONS: Results
      suggest that full effect of the non-intertemporal aspects of smoking (e.g., the
      substitution of cigarettes for food) on BMI scores may be underestimated in
      previous studies that fail to account for the mitigating influence of time
      preference.

PMID- 18725894
TI  - Undernutrition during suckling in rats elevates plasma adiponectin and its
      receptor in skeletal muscle regardless of diet composition: a protective effect?
AB  - OBJECTIVE: Nutrition during critical periods in early life may increase the
      subsequent risk of obesity, hypertension and metabolic diseases in adulthood. Few
      studies have focused on the long-term consequences of poor nutrition during the
      suckling period on the susceptibility to developing obesity when exposed to a
      palatable cafeteria-style high-fat diet (CD) after weaning. DESIGN: This study
      examined the impact of early undernutrition, followed by CD exposure, on blood
      pressure, hormones and genes important for insulin sensitivity and metabolism and
      skeletal muscle mRNA expression of adiponectin receptor 1 (AdipoR1), carnitine
      palmitoyl-transferase I (CPT-1), cytochrome c oxidase 4 (COX4) and peroxisome
      proliferator-activated receptor alpha (PPARalpha). Following normal gestation,
      Sprague-Dawley rat litters were adjusted to 18 (undernourished) or 12 (control)
      pups. Rats were weaned (day 21) onto either palatable CD or standard chow.
      RESULTS: Early undernourished rats were significantly lighter than control by 17
      days, persisting into adulthood only when animals were fed chow after weaning.
      Regardless of litter size, rats fed CD had doubled fat mass at 15 weeks of age,
      and significant elevations in plasma leptin, insulin and adiponectin.
      Importantly, undernutrition confined to the suckling period, elevated circulating
      adiponectin regardless of post-weaning diet. Blood pressure was reduced in early
      undernourished rats fed chow, and increased by CD. Early undernutrition was
      associated with long-term elevations in the expression of AdipoR1, CPT-1, COX4
      and PPARalpha in skeletal muscle. CONCLUSION: This study demonstrates the
      important role of early nutrition on body weight and metabolism, suggesting early
      undernourishment enhances insulin sensitivity and fatty-acid oxidation. The long
      term potential benefit of limiting nutrition in the early postnatal period
      warrants further investigation.

PMID- 18725895
TI  - Urinary sucrose and fructose as biomarkers of sugar consumption: comparison of
      normal weight and obese volunteers.
AB  - Using urinary sugars as a biomarker of consumption, we have previously shown that
      obese people consume significantly more sugars than individuals of normal weight.
      However, there is concern that recovery of this biomarker may differ between
      normal weight and obese individuals. A total of 19 subjects, divided into two
      groups according to their body mass index (BMI) (normal weight BMI < or = 25
      kg/m(2), n=10; obese BMI > or = 30 kg/m(2), n=9), participated in a randomized
      crossover dietary intervention study of three diets providing 13, 30 and 50% of
      energy from sugars for 4 days each while living in a volunteer suite. The mean
      urinary sucrose and fructose excretions in 24-h urine increased with increasing
      sugar consumption over the three dietary periods in both BMI groups and were
      significantly different between the diets (P < 0.01). There was no significant
      interaction effect of BMI class on the mean urinary excretions of these sugars
      with different sugar intakes, either as absolute values or expressed as a
      percentage of total sugar intake. In conclusion, BMI does not affect the validity
      of sucrose and fructose excretions in 24-h urine collections used as biomarkers
      to estimate total sugar consumption.

PMID- 18725897
TI  - Credibility crisis in pediatric psychiatry.

PMID- 18725896
TI  - A case of permanent pacemaker lead infection.
AB  - BACKGROUND: A 70-year-old man with diabetes mellitus, fever of unknown origin and
      oliguria was admitted to hospital. Blood cultures were positive for a
      Staphylococcus aureus infection and antibiotic therapy was started. A year
      previously the patient had received a DDD pacemaker to treat sick sinus syndrome
      with intermittent atrioventricular block. Transthoracic echocardiography showed
      severe tricuspid regurgitation and a mass attached to the ventricular pacemaker
      lead; transesophageal echocardiography showed the same finding but additionally
      showed a vegetation on the tricuspid septal leaflet and a mass attached to the
      atrial pacemaker lead. Coronary angiography revealed a lesion that occluded 70%
      of the proximal left anterior descending artery and occlusion of the proximal
      right coronary artery. INVESTIGATIONS: Electrocardiography, transthoracic
      echocardiography, transesophageal echocardiography, multidetector thoracic CT,
      coronary angiography, blood cultures and laboratory testing. DIAGNOSIS: Pacemaker
      lead infection and tricuspid valve endocarditis. MANAGEMENT: The patient was
      surgically treated under cardiopulmonary bypass during which the pacemaker system
      was removed and an accurate debridement of the tricuspid tissue was performed.

PMID- 18725898
TI  - The injured brain.

PMID- 18725899
TI  - Epigenetic control of myelin repair.
AB  - Although the CNS has a robust innate ability to repair demyelinated axons, this
      capacity appears to dissipate with age. A study in this issue suggests that
      epigenetic processes participate in myelin repair and that the epigenetic
      response is less dynamic in older individuals.

PMID- 18725900
TI  - Octopamine fuels fighting flies.
AB  - The neural basis of aggression is poorly understood. A study in this issue used
      genetic scalpels to dissect the circuitry of the fly brain and identified a small
      cluster of octopaminergic neurons that can make a fly fighting mad.

PMID- 18725902
TI  - Rhythms of memory.
AB  - Mitogen-activated Protein Kinases (MAPKs) are critical for the formation of
      stable long-term memories. New work shows that circadian MAPK activity cycling is
      important in the formation of new hippocampus-dependent memories.

PMID- 18725901
TI  - Finding coherence in spontaneous oscillations.
AB  - Spontaneous ultra-slow oscillations in brain signals are ubiquitous, although
      their source and function remain unknown. A new study now reports that this
      activity is correlated between functionally related areas across hemispheres in
      humans.

PMID- 18725903
TI  - Is radioiodine more likely than antithyroid drugs to worsen ophthalmopathy in
      patients with Graves disease?

PMID- 18725904
TI  - Does growth hormone therapy benefit body composition and glucose homeostasis in
      girls with Turner syndrome?

PMID- 18725905
TI  - New-onset diabetes in an obese adolescent: diagnostic dilemmas.
AB  - BACKGROUND: A 14-year-old, obese, African American boy presented to his
      pediatrician with polyuria, polydipsia, and a significant unintentional weight
      loss. He was dehydrated, with high levels of blood sugar and urinary ketones. He
      had no history of previous illnesses and was not taking any medications. He had a
      family history of type 2 diabetes mellitus. INVESTIGATIONS: Physical examination
      included assessing stigmata of insulin resistance, and measuring blood pressure,
      pulse, and BMI. Blood samples were obtained for measurement of venous blood pH,
      bicarbonate, serum glucose, electrolytes, HbA(1C), aminotransferases and lipids.
      Urine was sampled for measurement of ketones. Subsequently, measurements of
      fasting C-peptide and immunoassays for insulin autoantibodies (IAA), islet-cell
      autoantibodies (ICA-512) and glutamic acid decarboxylase autoantibodies (GAD-65)
      were performed. DIAGNOSIS: New-onset diabetes mellitus with diabetic
      ketoacidosis, initially diagnosed as type 2 diabetes mellitus, but later
      determined as type 1 diabetes mellitus. MANAGEMENT: After treatment of diabetic
      ketoacidosis with hydration and insulin infusion, the patient was discharged on
      subcutaneous insulin. He was diagnosed with type 2 diabetes mellitus and was
      transferred to oral insulin-sensitizing agents. He re-presented 18 months later
      with an insulin requirement during an asthma exacerbation treated with steroids.
      Due to the worsening of his diabetic symptoms, the patient was tested for islet
      autoantibodies and was found to be positive for GAD-65 and IAA, that is,
      diagnostic of type 1 diabetes mellitus. He has continued to require subcutaneous
      insulin.

PMID- 18725906
TI  - Is secretion of glucagon-like peptide-1 reduced in type 2 diabetes mellitus?

PMID- 18725907
TI  - Moving towards the use of targeted therapies in thyroid cancer.

PMID- 18725910
TI  - What is the optimal management approach for pediatric patients with severe
      ulcerative colitis?

PMID- 18725908
TI  - Soybean GmMYB76, GmMYB92, and GmMYB177 genes confer stress tolerance in
      transgenic Arabidopsis plants.
AB  - MYB-type transcription factors contain the conserved MYB DNA-binding domain of
      approximately 50 amino acids and are involved in the regulation of many aspects
      of plant growth, development, metabolism and stress responses. From soybean
      plants, we identified 156 GmMYB genes using our previously obtained 206 MYB
      unigenes, and 48 were found to have full-length open-reading frames. Expressions
      of all these identified genes were examined, and we found that expressions of 43
      genes were changed upon treatment with ABA, salt, drought and/or cold stress.
      Three GmMYB genes, GmMYB76, GmMYB92 and GmMYB177, were chosen for further
      analysis. Using the yeast assay system, GmMYB76 and GmMYB92 were found to have
      transactivation activity and can form homodimers. GmMYB177 did not appear to have
      transactivation activity but can form heterodimers with GmMYB76. Yeast one-hybrid
      assay revealed that all the three GmMYBs could bind to cis-elements TAT AAC GGT
      TTT TT and CCG GAA AAA AGG AT, but with different affinity, and GmMYB92 could
      also bind to TCT CAC CTA CC. The transgenic Arabidopsis plants overexpressing
      GmMYB76 or GmMYB177 showed better performance than the GmMYB92-transgenic plants
      in salt and freezing tolerance. However, these transgenic plants exhibited
      reduced sensitivity to ABA treatment at germination stage in comparison with the
      wild-type plants. The three GmMYB genes differentially affected a subset of
      stress-responsive genes in addition to their regulation of a common subset of
      stress-responsive genes. These results indicate that the three GmMYB genes may
      play differential roles in stress tolerance, possibly through regulation of
      stress-responsive genes.

PMID- 18725911
TI  - Dietary counseling or dietary supplementation for malnourished patients with
      chronic pancreatitis?

PMID- 18725912
TI  - The epidemiology of obsessive-compulsive disorder in the National Comorbidity
      Survey Replication.
AB  - Despite significant advances in the study of obsessive-compulsive disorder (OCD),
      important questions remain about the disorder's public health significance,
      appropriate diagnostic classification, and clinical heterogeneity. These issues
      were explored using data from the National Comorbidity Survey Replication, a
      nationally representative survey of US adults. A subsample of 2073 respondents
      was assessed for lifetime Diagnostic and Statistical Manual of Mental Disorders,
      4th edn (DSM-IV) OCD. More than one quarter of respondents reported experiencing
      obsessions or compulsions at some time in their lives. While conditional
      probability of OCD was strongly associated with the number of obsessions and
      compulsions reported, only small proportions of respondents met full DSM-IV
      criteria for lifetime (2.3%) or 12-month (1.2%) OCD. OCD is associated with
      substantial comorbidity, not only with anxiety and mood disorders but also with
      impulse-control and substance use disorders. Severity of OCD, assessed by an
      adapted version of the Yale-Brown Obsessive Compulsive Scale, is associated with
      poor insight, high comorbidity, high role impairment, and high probability of
      seeking treatment. The high prevalence of subthreshold OCD symptoms may help
      explain past inconsistencies in prevalence estimates across surveys and suggests
      that the public health burden of OCD may be greater than its low prevalence
      implies. Evidence of a preponderance of early onset cases in men, high
      comorbidity with a wide range of disorders, and reliable associations between
      disorder severity and key outcomes may have implications for how OCD is
      classified in DSM-V.

PMID- 18725913
TI  - Association of prealbumin level with mortality in patients with acute kidney
      injury.
AB  - Acute kidney injury (AKI) is common in hospitalized patients, a population with a
      high prevalence of malnutrition. Pre-existing malnutrition is associated with
      adverse outcomes in patients with AKI. This Practice Point commentary discusses a
      study by Perez Valdevieso et al. that examined the association between serum
      prealbumin level and mortality in patients with AKI. Adjusted multivariate
      analyses showed that a serum prealbumin level below the group median (11 mg/dl)
      was independently predictive of in-hospital mortality and that for every 5 mg/dl
      increase in serum prealbumin level, in-hospital mortality decreased by 29%. A
      decreased serum prealbumin concentration at the time of renal consultation for
      AKI independently predicted poor prognosis. It is unknown whether this adverse
      prognostic association is primarily caused by malnutrition, a negative acute
      phase response to inflammation, transcapillary leak, or a combination of factors.
      Serum prealbumin levels may aid prognostic stratification and clinical decision
      making in AKI and should be included in future studies. There is no evidence that
      attempting to raise low prealbumin levels through aggressive nutritional support
      improves outcomes in AKI.

PMID- 18725914
TI  - More-intensive renal replacement therapy has no benefit in critically ill
      patients with acute kidney injury.

PMID- 18725915
TI  - Is it beneficial to treat hypertension in patients aged 80 years or older?
AB  - Blood pressure lowering has clear beneficial effects in terms of reducing the
      risk of stroke, cardiovascular events and cardiovascular mortality in the general
      population, but it is unclear whether treating hypertension in individuals aged
      >or=80 years is beneficial. This Practice Point commentary discusses a recent
      randomized, prospective study by Beckett et al., which found that
      antihypertensive therapy with indapamide-with or without perindopril--was
      associated with significant decreases in the rate of death from stroke, rate of
      heart failure and risk of all--cause mortality in individuals aged 80 years or
      older. These results indicate that treating hypertension in individuals in this
      age-group is no longer contraindicated because of a lack of evidence.

PMID- 18725916
TI  - Remission of proteinuria in primary glomerulonephritis: we know the goal but do
      we know the price?
AB  - Membranous nephropathy, focal segmental glomerulosclerosis and IgA nephropathy
      are the most commonly recognized types of primary glomerulonephritis that
      progress to end-stage renal disease. Persistent proteinuria is a major
      determinant of such progression. Reduction of proteinuria slows progression of
      renal disease and improves renal survival, but many of the agents used to reduce
      proteinuria carry a considerable risk of toxicity. The assessment of benefit
      versus risk of these medications can be further complicated by the temporal
      disconnect between the onset of benefit and of serious adverse events. In
      addition, relapses are common in these disorders and there is often a need for
      retreatment. Such retreatment might lead to repeated and/or prolonged drug
      exposure and to the oversight or underestimation of the cumulative dose of these
      agents because of the potentially extended interval between relapses.
      Consequently, it is very important to constantly review each patient's status and
      take into account their age, comorbid conditions and cumulative drug exposure
      when assessing treatment options. The potentially delayed development of adverse
      events also emphasizes the need for long-term surveillance of patients who
      receive immunosuppressive treatment for glomerular disease, often well beyond
      their drug exposure period and even when the treatment has been successful.

PMID- 18725917
TI  - Lymphocyte depletion for kidney transplantation: back to the past?

PMID- 18725918
TI  - Neuroimaging, impaired states of consciousness, and public outreach.

PMID- 18725919
TI  - Eye signs in patients with parkinsonism: do they predict the development of
      multiple system atrophy?

PMID- 18725920
TI  - Neuroleptic discontinuation during dementia care: a recent trial and its
      implications for practice.

PMID- 18725921
TI  - Concomitant DFMO and sulindac chemoprevention of colorectal adenomas: a major
      clinical advance.
AB  - In a randomized, placebo-controlled, double-blind clinical trial by Meyskens et
      al. the combination of difluoromethylornithine and sulindac has been shown to be
      strikingly effective for prevention of sporadic colorectal adenomas. This
      concomitant use of two drugs to suppress the progression of preneoplastic lesions
      represents the first major clinical success of the application of the principle
      of 'combination chemoprevention'. Neither drug alone has previously had clinical
      utility at the low doses used in this trial. The combination of the two agents
      has provided synergistic efficacy in suppression of carcinogenesis, while
      minimizing any undesirable adverse effects. This study should be the impetus for
      further clinical investigation of the use of multiple drugs for chemoprevention
      of cancer.

PMID- 18725922
TI  - The impact of histopathologic diagnosis on the proper management of testis
      neoplasms.
AB  - BACKGROUND: A 45-year-old man underwent a right orchiectomy for a rapidly growing
      testicular mass. After histologic and imaging examinations the patient was
      diagnosed with stage I (T1N0M0) seminoma. Approximately 2 months after surgery
      the patient began to complain of abdominal pain and a CT scan revealed a bulky
      retroperitoneal mass. The patient did not receive the planned prophylactic
      radiotherapy and was treated with combined cisplatin, etoposide and bleomycin
      chemotherapy; after the completion of this treatment he achieved complete
      remission. Three years later, and while still undergoing follow-up, the patient
      developed multiple neurological motor deficits. INVESTIGATIONS: Brain MRI and CT
      guided biopsy. DIAGNOSIS: Diffuse large B-cell lymphoma of the testis, relapsing
      in the central nervous system. MANAGEMENT: High-dose methotrexate alone or in
      combination with high-dose cytarabine.

PMID- 18725923
TI  - Host control of malaria infections: constraints on immune and erythropoeitic
      response kinetics.
AB  - The two main agents of human malaria, Plasmodium vivax and Plasmodium falciparum,
      can induce severe anemia and provoke strong, complex immune reactions. Which
      dynamical behaviors of host immune and erythropoietic responses would foster
      control of infection, and which would lead to runaway parasitemia and/or severe
      anemia? To answer these questions, we developed differential equation models of
      interacting parasite and red blood cell (RBC) populations modulated by host
      immune and erythropoietic responses. The model immune responses incorporate both
      a rapidly responding innate component and a slower-responding, long-term antibody
      component, with several parasite developmental stages considered as targets for
      each type of immune response. We found that simulated infections with the highest
      parasitemia tended to be those with ineffective innate immunity even if
      antibodies were present. We also compared infections with dyserythropoiesis
      (reduced RBC production during infection) to those with compensatory
      erythropoiesis (boosted RBC production) or a fixed basal RBC production rate.
      Dyserythropoiesis tended to reduce parasitemia slightly but at a cost to the host
      of aggravating anemia. On the other hand, compensatory erythropoiesis tended to
      reduce the severity of anemia but with enhanced parasitemia if the innate
      response was ineffective. For both parasite species, sharp transitions between
      the schizont and the merozoite stages of development (i.e., with standard
      deviation in intra-RBC development time <or=2.4 h) were associated with lower
      parasitemia and less severe anemia. Thus tight synchronization in asexual
      parasite development might help control parasitemia. Finally, our simulations
      suggest that P. vivax can induce severe anemia as readily as P. falciparum for
      the same type of immune response, though P. vivax attacks a much smaller subset
      of RBCs. Since most P. vivax infections are nonlethal (if debilitating)
      clinically, this suggests that P. falciparum adaptations for countering or
      evading immune responses are more effective than those of P. vivax.

PMID- 18725924
TI  - The effect of a DeltaK280 mutation on the unfolded state of a microtubule-binding
      repeat in Tau.
AB  - Tau is a natively unfolded protein that forms intracellular aggregates in the
      brains of patients with Alzheimer's disease. To decipher the mechanism underlying
      the formation of tau aggregates, we developed a novel approach for constructing
      models of natively unfolded proteins. The method, energy-minima mapping and
      weighting (EMW), samples local energy minima of subsequences within a natively
      unfolded protein and then constructs ensembles from these energetically favorable
      conformations that are consistent with a given set of experimental data. A unique
      feature of the method is that it does not strive to generate a single ensemble
      that represents the unfolded state. Instead we construct a number of candidate
      ensembles, each of which agrees with a given set of experimental constraints, and
      focus our analysis on local structural features that are present in all of the
      independently generated ensembles. Using EMW we generated ensembles that are
      consistent with chemical shift measurements obtained on tau constructs. Thirty
      models were constructed for the second microtubule binding repeat (MTBR2) in wild
      type (WT) tau and a DeltaK280 mutant, which is found in some forms of
      frontotemporal dementia. By focusing on structural features that are preserved
      across all ensembles, we find that the aggregation-initiating sequence, PHF6*,
      prefers an extended conformation in both the WT and DeltaK280 sequences. In
      addition, we find that residue K280 can adopt a loop/turn conformation in WT
      MTBR2 and that deletion of this residue, which can adopt nonextended states,
      leads to an increase in locally extended conformations near the C-terminus of
      PHF6*. As an increased preference for extended states near the C-terminus of
      PHF6* may facilitate the propagation of beta-structure downstream from PHF6*,
      these results explain how a deletion at position 280 can promote the formation of
      tau aggregates.

PMID- 18725926
TI  - Viral paratransgenesis in the malaria vector Anopheles gambiae.
AB  - Paratransgenesis, the genetic manipulation of insect symbiotic microorganisms, is
      being considered as a potential method to control vector-borne diseases such as
      malaria. The feasibility of paratransgenic malaria control has been hampered by
      the lack of candidate symbiotic microorganisms for the major vector Anopheles
      gambiae. In other systems, densonucleosis viruses (DNVs) are attractive agents
      for viral paratransgenesis because they infect important vector insects, can be
      genetically manipulated and are transmitted to subsequent generations. However,
      An. gambiae has been shown to be refractory to DNV dissemination. We discovered,
      cloned and characterized the first known DNV (AgDNV) capable of infection and
      dissemination in An. gambiae. We developed a flexible AgDNV-based expression
      vector to express any gene of interest in An. gambiae using a two-plasmid helper
      transducer system. To demonstrate proof-of-concept of the viral paratransgenesis
      strategy, we used this system to transduce expression of an exogenous gene
      (enhanced green fluorescent protein; EGFP) in An. gambiae mosquitoes. Wild-type
      and EGFP-transducing AgDNV virions were highly infectious to An. gambiae larvae,
      disseminated to and expressed EGFP in epidemiologically relevant adult tissues
      such as midgut, fat body and ovaries and were transmitted to subsequent mosquito
      generations. These proof-of-principle data suggest that AgDNV could be used as
      part of a paratransgenic malaria control strategy by transduction of anti
      Plasmodium peptides or insect-specific toxins in Anopheles mosquitoes. AgDNV will
      also be extremely valuable as an effective and easy-to-use laboratory tool for
      transient gene expression or RNAi in An. gambiae.

PMID- 18725925
TI  - Molecular epidemiology of A/H3N2 and A/H1N1 influenza virus during a single
      epidemic season in the United States.
AB  - To determine the spatial and temporal dynamics of influenza A virus during a
      single epidemic, we examined whole-genome sequences of 284 A/H1N1 and 69 A/H3N2
      viruses collected across the continental United States during the 2006-2007
      influenza season, representing the largest study of its kind undertaken to date.
      A phylogenetic analysis revealed that multiple clades of both A/H1N1 and A/H3N2
      entered and co-circulated in the United States during this season, even in
      localities that are distant from major metropolitan areas, and with no clear
      pattern of spatial spread. In addition, co-circulating clades of the same subtype
      exchanged genome segments through reassortment, producing both a minor clade of
      A/H3N2 viruses that appears to have re-acquired sensitivity to the adamantane
      class of antiviral drugs, as well as a likely antigenically distinct A/H1N1 clade
      that became globally dominant following this season. Overall, the co-circulation
      of multiple viral clades during the 2006-2007 epidemic season revealed patterns
      of spatial spread that are far more complex than observed previously, and
      suggests a major role for both migration and reassortment in shaping the
      epidemiological dynamics of human influenza A virus.

PMID- 18725927
TI  - Modeling ChIP sequencing in silico with applications.
AB  - ChIP sequencing (ChIP-seq) is a new method for genomewide mapping of protein
      binding sites on DNA. It has generated much excitement in functional genomics. To
      score data and determine adequate sequencing depth, both the genomic background
      and the binding sites must be properly modeled. To develop a computational
      foundation to tackle these issues, we first performed a study to characterize the
      observed statistical nature of this new type of high-throughput data. By linking
      sequence tags into clusters, we show that there are two components to the
      distribution of tag counts observed in a number of recent experiments: an initial
      power-law distribution and a subsequent long right tail. Then we develop in
      silico ChIP-seq, a computational method to simulate the experimental outcome by
      placing tags onto the genome according to particular assumed distributions for
      the actual binding sites and for the background genomic sequence. In contrast to
      current assumptions, our results show that both the background and the binding
      sites need to have a markedly nonuniform distribution in order to correctly model
      the observed ChIP-seq data, with, for instance, the background tag counts modeled
      by a gamma distribution. On the basis of these results, we extend an existing
      scoring approach by using a more realistic genomic-background model. This enables
      us to identify transcription-factor binding sites in ChIP-seq data in a
      statistically rigorous fashion.

PMID- 18725928
TI  - Divergent evolution of CHD3 proteins resulted in MOM1 refining epigenetic control
      in vascular plants.
AB  - Arabidopsis MOM1 is required for the heritable maintenance of transcriptional
      gene silencing (TGS). Unlike many other silencing factors, depletion of MOM1
      evokes transcription at selected loci without major changes in DNA methylation or
      histone modification. These loci retain unusual, bivalent chromatin properties,
      intermediate to both euchromatin and heterochromatin. The structure of MOM1
      previously suggested an integral nuclear membrane protein with chromatin
      remodeling and actin-binding activities. Unexpected results presented here
      challenge these presumed MOM1 activities and demonstrate that less than 13% of
      MOM1 sequence is necessary and sufficient for TGS maintenance. This active
      sequence encompasses a novel Conserved MOM1 Motif 2 (CMM2). The high conservation
      suggests that CMM2 has been the subject of strong evolutionary pressure. The
      replacement of Arabidopsis CMM2 by a poplar motif reveals its functional
      conservation. Interspecies comparison suggests that MOM1 proteins emerged at the
      origin of vascular plants through neo-functionalization of the ubiquitous
      eukaryotic CHD3 chromatin remodeling factors. Interestingly, despite the
      divergent evolution of CHD3 and MOM1, we observed functional cooperation in
      epigenetic control involving unrelated protein motifs and thus probably diverse
      mechanisms.

PMID- 18725929
TI  - Structure and dynamics of interphase chromosomes.
AB  - During interphase chromosomes decondense, but fluorescent in situ hybridization
      experiments reveal the existence of distinct territories occupied by individual
      chromosomes inside the nuclei of most eukaryotic cells. We use computer
      simulations to show that the existence and stability of territories is a kinetic
      effect that can be explained without invoking an underlying nuclear scaffold or
      protein-mediated interactions between DNA sequences. In particular, we show that
      the experimentally observed territory shapes and spatial distances between marked
      chromosome sites for human, Drosophila, and budding yeast chromosomes can be
      reproduced by a parameter-free minimal model of decondensing chromosomes. Our
      results suggest that the observed interphase structure and dynamics are due to
      generic polymer effects: confined Brownian motion conserving the local
      topological state of long chain molecules and segregation of mutually unentangled
      chains due to topological constraints.

PMID- 18725930
TI  - Genic and global functions for Paf1C in chromatin modification and gene
      expression in Arabidopsis.
AB  - In budding yeast, intragenic histone modification is linked with transcriptional
      elongation through the conserved regulator Paf1C. To investigate Paf1C-related
      function in higher eukaryotes, we analyzed the effects of loss of Paf1C on
      histone H3 density and patterns of H3 methylated at K4, K27, and K36 in
      Arabidopsis genes, and integrated this with existing gene expression data. Loss
      of Paf1C did not change global abundance of H3K4me3 or H3K36me2 within chromatin,
      but instead led to a 3' shift in the distribution of H3K4me3 and a 5' shift in
      the distribution of H3K36me2 within genes. We found that genes regulated by plant
      Paf1C showed strong enrichment for both H3K4me3 and H3K27me3 and also showed a
      high degree of tissue-specific expression. At the Paf1C- and PcG-regulated gene
      FLC, transcriptional silencing and loss of H3K4me3 and H3K36me2 were accompanied
      by expansion of H3K27me3 into the promoter and transcriptional start regions and
      further enrichment of H3K27me3 within the transcribed region. These results
      highlight both genic and global functions for plant Paf1C in histone modification
      and gene expression, and link transcriptional activity with cellular memory.

PMID- 18725931
TI  - C. elegans nucleostemin is required for larval growth and germline stem cell
      division.
AB  - The nucleolus has shown to be integral for many processes related to cell growth
      and proliferation. Stem cells in particular are likely to depend upon nucleolus
      based processes to remain in a proliferative state. A highly conserved nucleolar
      factor named nucleostemin is proposed to be a critical link between nucleolar
      function and stem-cell-specific processes. Currently, it is unclear whether
      nucleostemin modulates proliferation by affecting ribosome biogenesis or by
      another nucleolus-based activity that is specific to stem cells and/or highly
      proliferating cells. Here, we investigate nucleostemin (nst-1) in the nematode C.
      elegans, which enables us to examine nst-1 function during both proliferation and
      differentiation in vivo. Like mammalian nucleostemin, the NST-1 protein is
      localized to the nucleolus and the nucleoplasm; however, its expression is found
      in both differentiated and proliferating cells. Global loss of C. elegans
      nucleostemin (nst-1) leads to a larval arrest phenotype due to a growth defect in
      the soma, while loss of nst-1 specifically in the germ line causes germline stem
      cells to undergo a cell cycle arrest. nst-1 mutants exhibit reduced levels of
      rRNAs, suggesting defects in ribosome biogenesis. However, NST-1 is generally not
      present in regions of the nucleolus where rRNA transcription and processing
      occurs, so this reduction is likely secondary to a different defect in ribosome
      biogenesis. Transgenic studies indicate that NST-1 requires its N-terminal domain
      for stable expression and both its G1 GTPase and intermediate domains for proper
      germ line function. Our data support a role for C. elegans nucleostemin in cell
      growth and proliferation by promoting ribosome biogenesis.

PMID- 18725932
TI  - Deep sequencing analysis of small noncoding RNA and mRNA targets of the global
      post-transcriptional regulator, Hfq.
AB  - Recent advances in high-throughput pyrosequencing (HTPS) technology now allow a
      thorough analysis of RNA bound to cellular proteins, and, therefore, of post
      transcriptional regulons. We used HTPS to discover the Salmonella RNAs that are
      targeted by the common bacterial Sm-like protein, Hfq. Initial transcriptomic
      analysis revealed that Hfq controls the expression of almost a fifth of all
      Salmonella genes, including several horizontally acquired pathogenicity islands
      (SPI-1, -2, -4, -5), two sigma factor regulons, and the flagellar gene cascade.
      Subsequent HTPS analysis of 350,000 cDNAs, derived from RNA co
      immunoprecipitation (coIP) with epitope-tagged Hfq or control coIP, identified
      727 mRNAs that are Hfq-bound in vivo. The cDNA analysis discovered new, small
      noncoding RNAs (sRNAs) and more than doubled the number of sRNAs known to be
      expressed in Salmonella to 64; about half of these are associated with Hfq. Our
      analysis explained aspects of the pleiotropic effects of Hfq loss-of-function.
      Specifically, we found that the mRNAs of hilD (master regulator of the SPI-1
      invasion genes) and flhDC (flagellar master regulator) were bound by Hfq. We
      predicted that defective SPI-1 secretion and flagellar phenotypes of the hfq
      mutant would be rescued by overexpression of HilD and FlhDC, and we proved this
      to be correct. The combination of epitope-tagging and HTPS of immunoprecipitated
      RNA detected the expression of many intergenic chromosomal regions of Salmonella.
      Our approach overcomes the limited availability of high-density microarrays that
      have impeded expression-based sRNA discovery in microorganisms. We present a
      generic strategy that is ideal for the systems-level analysis of the post
      transcriptional regulons of RNA-binding proteins and for sRNA discovery in a wide
      range of bacteria.

PMID- 18725933
TI  - An Sp1/Sp3 binding polymorphism confers methylation protection.
AB  - Hundreds of genes show aberrant DNA hypermethylation in cancer, yet little is
      known about the causes of this hypermethylation. We identified RIL as a frequent
      methylation target in cancer. In search for factors that influence RIL
      hypermethylation, we found a 12-bp polymorphic sequence around its transcription
      start site that creates a long allele. Pyrosequencing of homozygous tumors
      revealed a 2.1-fold higher methylation for the short alleles (P<0.001). Bisulfite
      sequencing of cancers heterozygous for RIL showed that the short alleles are 3.1
      fold more methylated than the long (P<0.001). The comparison of expression levels
      between unmethylated long and short EBV-transformed cell lines showed no
      difference in expression in vivo. Electrophorectic mobility shift assay showed
      that the inserted region of the long allele binds Sp1 and Sp3 transcription
      factors, a binding that is absent in the short allele. Transient transfection of
      RIL allele-specific transgenes showed no effects of the additional Sp1 site on
      transcription early on. However, stable transfection of methylation-seeded
      constructs showed gradually decreasing transcription levels from the short allele
      with eventual spreading of de novo methylation. In contrast, the long allele
      showed stable levels of expression over time as measured by luciferase and
      approximately 2-3-fold lower levels of methylation by bisulfite sequencing
      (P<0.001), suggesting that the polymorphic Sp1 site protects against time
      dependent silencing. Our finding demonstrates that, in some genes,
      hypermethylation in cancer is dictated by protein-DNA interactions at the
      promoters and provides a novel mechanism by which genetic polymorphisms can
      influence an epigenetic state.

PMID- 18725934
TI  - Identification and functional analysis of light-responsive unique genes and gene
      family members in rice.
AB  - Functional redundancy limits detailed analysis of genes in many organisms. Here,
      we report a method to efficiently overcome this obstacle by combining gene
      expression data with analysis of gene-indexed mutants. Using a rice NSF45K oligo
      microarray to compare 2-week-old light- and dark-grown rice leaf tissue, we
      identified 365 genes that showed significant 8-fold or greater induction in the
      light relative to dark conditions. We then screened collections of rice T-DNA
      insertional mutants to identify rice lines with mutations in the strongly light
      induced genes. From this analysis, we identified 74 different lines comprising
      two independent mutant lines for each of 37 light-induced genes. This list was
      further refined by mining gene expression data to exclude genes that had
      potential functional redundancy due to co-expressed family members (12 genes) and
      genes that had inconsistent light responses across other publicly available
      microarray datasets (five genes). We next characterized the phenotypes of rice
      lines carrying mutations in ten of the remaining candidate genes and then carried
      out co-expression analysis associated with these genes. This analysis effectively
      provided candidate functions for two genes of previously unknown function and for
      one gene not directly linked to the tested biochemical pathways. These data
      demonstrate the efficiency of combining gene family-based expression profiles
      with analyses of insertional mutants to identify novel genes and their functions,
      even among members of multi-gene families.

PMID- 18725935
TI  - Bacillus anthracis secretes proteins that mediate heme acquisition from
      hemoglobin.
AB  - Acquisition of iron is necessary for the replication of nearly all bacterial
      pathogens; however, iron of vertebrate hosts is mostly sequestered by heme and
      bound to hemoglobin within red blood cells. In Bacillus anthracis, the spore
      forming agent of anthrax, the mechanisms of iron scavenging from hemoglobin are
      unknown. We report here that B. anthracis secretes IsdX1 and IsdX2, two NEAT
      domain proteins, to remove heme from hemoglobin, thereby retrieving iron for
      bacterial growth. Unlike other Gram-positive bacteria, which rely on cell wall
      anchored Isd proteins for heme scavenging, B. anthracis seems to have also
      evolved NEAT domain proteins in the extracellular milieu and in the bacterial
      envelope to provide for the passage of heme.

PMID- 18725936
TI  - HIV traffics through a specialized, surface-accessible intracellular compartment
      during trans-infection of T cells by mature dendritic cells.
AB  - In vitro, dendritic cells (DCs) bind and transfer intact, infectious HIV to CD4 T
      cells without first becoming infected, a process known as trans-infection. trans
      infection is accomplished by recruitment of HIV and its receptors to the site of
      DC-T cell contact and transfer of virions at a structure known as the infectious
      synapse. In this study, we used fluorescent microscopy to track individual HIV
      particles trafficking in DCs during virus uptake and trans-infection. Mature DCs
      rapidly concentrated HIV into an apparently intracellular compartment that lacked
      markers characteristic of early endosomes, lysosomes, or antigen-processing
      vesicles. Live cell microscopy demonstrated that the HIV-containing compartment
      was rapidly polarized toward the infectious synapse after contact with a T cell;
      however, the bulk of the concentrated virus remained in the DCs after T cell
      engagement. Individual virions were observed emerging from the compartment and
      fusing with the T cell membrane at the infectious synapse. The compartmentalized
      HIV, although engulfed by the cytoplasm, was fully accessible to HIV envelope
      specific inhibitors and other membrane-impermeable probes that were delivered to
      the cell surface. These results demonstrate that HIV resides in an invaginated
      domain within DCs that is both contiguous with the plasma membrane and distinct
      from endocytic vesicles. We conclude that HIV virions are routed through this
      specialized compartment, which allows individual particles to be delivered to T
      cells during trans-infection.

PMID- 18725937
TI  - Evolutionary and transmission dynamics of reassortant H5N1 influenza virus in
      Indonesia.
AB  - H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the
      Asian poultry industry since their recurrence in 2003. The viruses pose a threat
      of emergence of a global pandemic influenza through point mutation or
      reassortment leading to a strain that can effectively transmit among humans. In
      this study, we present phylogenetic evidences for the interlineage reassortment
      among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and
      identify the potential genetic parents of the reassorted genome segments.
      Parsimony analyses of viral phylogeography suggest that the reassortant viruses
      may have originated from greater Jakarta and surroundings, and subsequently
      spread to other regions in the West Java province. In addition, Bayesian methods
      were used to elucidate the genetic diversity dynamics of the reassortant strain
      and one of its genetic parents, which revealed a more rapid initial growth of
      genetic diversity in the reassortant viruses relative to their genetic parent.
      These results demonstrate that interlineage exchange of genetic information may
      play a pivotal role in determining viral genetic diversity in a focal population.
      Moreover, our study also revealed significantly stronger diversifying selection
      on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence
      of the reassortant viruses, respectively. We discuss how the corresponding
      mutations might drive the adaptation and onward transmission of the newly formed
      reassortant viruses.

PMID- 18725938
TI  - HIV-1 Nef targets MHC-I and CD4 for degradation via a final common beta-COP
      dependent pathway in T cells.
AB  - To facilitate viral infection and spread, HIV-1 Nef disrupts the surface
      expression of the viral receptor (CD4) and molecules capable of presenting HIV
      antigens to the immune system (MHC-I). To accomplish this, Nef binds to the
      cytoplasmic tails of both molecules and then, by mechanisms that are not well
      understood, disrupts the trafficking of each molecule in different ways.
      Specifically, Nef promotes CD4 internalization after it has been transported to
      the cell surface, whereas Nef uses the clathrin adaptor, AP-1, to disrupt normal
      transport of MHC-I from the TGN to the cell surface. Despite these differences in
      initial intracellular trafficking, we demonstrate that MHC-I and CD4 are
      ultimately found in the same Rab7(+) vesicles and are both targeted for
      degradation via the activity of the Nef-interacting protein, beta-COP. Moreover,
      we demonstrate that Nef contains two separable beta-COP binding sites. One site,
      an arginine (RXR) motif in the N-terminal alpha helical domain of Nef, is
      necessary for maximal MHC-I degradation. The second site, composed of a di-acidic
      motif located in the C-terminal loop domain of Nef, is needed for efficient CD4
      degradation. The requirement for redundant motifs with distinct roles supports a
      model in which Nef exists in multiple conformational states that allow access to
      different motifs, depending upon which cellular target is bound by Nef.

PMID- 18725939
TI  - Elusive origins of the extra genes in Aspergillus oryzae.
AB  - The genome sequence of Aspergillus oryzae revealed unexpectedly that this species
      has approximately 20% more genes than its congeneric species A. nidulans and A.
      fumigatus. Where did these extra genes come from? Here, we evaluate several
      possible causes of the elevated gene number. Many gene families are expanded in
      A. oryzae relative to A. nidulans and A. fumigatus, but we find no evidence of
      ancient whole-genome duplication or other segmental duplications, either in A.
      oryzae or in the common ancestor of the genus Aspergillus. We show that the
      presence of divergent pairs of paralogs is a feature peculiar to A. oryzae and is
      not shared with A. nidulans or A. fumigatus. In phylogenetic trees that include
      paralog pairs from A. oryzae, we frequently find that one of the genes in a pair
      from A. oryzae has the expected orthologous relationship with A. nidulans, A.
      fumigatus and other species in the subphylum Eurotiomycetes, whereas the other A.
      oryzae gene falls outside this clade but still within the Ascomycota. We
      identified 456 such gene pairs in A. oryzae. Further phylogenetic analysis did
      not however indicate a single consistent evolutionary origin for the divergent
      members of these pairs. Approximately one-third of them showed phylogenies that
      are suggestive of horizontal gene transfer (HGT) from Sordariomycete species, and
      these genes are closer together in the A. oryzae genome than expected by chance,
      but no unique Sordariomycete donor species was identifiable. The postulated HGTs
      from Sordariomycetes still leave the majority of extra A. oryzae genes
      unaccounted for. One possible explanation for our observations is that A. oryzae
      might have been the recipient of many separate HGT events from diverse donors.

PMID- 18725940
TI  - Predicting human nucleosome occupancy from primary sequence.
AB  - Nucleosomes are the fundamental repeating unit of chromatin and comprise the
      structural building blocks of the living eukaryotic genome. Micrococcal nuclease
      (MNase) has long been used to delineate nucleosomal organization. Microarray
      based nucleosome mapping experiments in yeast chromatin have revealed regularly
      spaced translational phasing of nucleosomes. These data have been used to train
      computational models of sequence-directed nuclesosome positioning, which have
      identified ubiquitous strong intrinsic nucleosome positioning signals. Here, we
      successfully apply this approach to nucleosome positioning experiments from human
      chromatin. The predictions made by the human-trained and yeast-trained models are
      strongly correlated, suggesting a shared mechanism for sequence-based
      determination of nucleosome occupancy. In addition, we observed striking
      complementarity between classifiers trained on experimental data from weakly
      versus heavily digested MNase samples. In the former case, the resulting model
      accurately identifies nucleosome-forming sequences; in the latter, the classifier
      excels at identifying nucleosome-free regions. Using this model we are able to
      identify several characteristics of nucleosome-forming and nucleosome-disfavoring
      sequences. First, by combining results from each classifier applied de novo
      across the human ENCODE regions, the classifier reveals distinct sequence
      composition and periodicity features of nucleosome-forming and nucleosome
      disfavoring sequences. Short runs of dinucleotide repeat appear as a hallmark of
      nucleosome-disfavoring sequences, while nucleosome-forming sequences contain
      short periodic runs of GC base pairs. Second, we show that nucleosome phasing is
      most frequently predicted flanking nucleosome-free regions. The results suggest
      that the major mechanism of nucleosome positioning in vivo is boundary-event
      driven and affirm the classical statistical positioning theory of nucleosome
      organization.

PMID- 18725941
TI  - Progesterone from the cumulus cells is the sperm chemoattractant secreted by the
      rabbit oocyte cumulus complex.
AB  - Sperm chemotaxis in mammals have been identified towards several female sources
      as follicular fluid (FF), oviduct fluid, and conditioned medium from the cumulus
      oophorus (CU) and the oocyte (O). Though several substances were confirmed as
      sperm chemoattractant, Progesterone (P) seems to be the best chemoattractant
      candidate, because: 1) spermatozoa express a cell surface P receptor, 2)
      capacitated spermatozoa are chemotactically attracted in vitro by gradients of
      low quantities of P; 3) the CU cells produce and secrete P after ovulation; 4) a
      gradient of P may be kept stable along the CU; and 5) the most probable site for
      sperm chemotaxis in vivo could be near and/or inside the CU. The aim of this
      study was to verify whether P is the sperm chemoattractant secreted by the rabbit
      oocyte-cumulus complex (OCC) in the rabbit, as a mammalian animal model. By means
      of videomicroscopy and computer image analysis we observed that only the CU are a
      stable source of sperm attractants. The CU produce and secrete P since the
      hormone was localized inside these cells by immunocytochemistry and in the
      conditioned medium by enzyme immunoassay. In addition, rabbit spermatozoa express
      a cell surface P receptor detected by western blot and localized over the
      acrosomal region by immunocytochemistry. To confirm that P is the sperm
      chemoattractant secreted by the CU, the sperm chemotactic response towards the
      OCC conditioned medium was inhibited by three different approaches: P from the
      OCC conditioned medium was removed with an anti-P antibody, the attractant
      gradient of the OCC conditioned medium was disrupted by a P counter gradient, and
      the sperm P receptor was blocked with a specific antibody. We concluded that only
      the CU but not the oocyte secretes P, and the latter chemoattract spermatozoa by
      means of a cell surface receptor. Our findings may be of interest in assisted
      reproduction procedures in humans, animals of economic importance and endangered
      species.

PMID- 18725942
TI  - A potential role for Drosophila mucins in development and physiology.
AB  - Vital vertebrate organs are protected from the external environment by a barrier
      that to a large extent consists of mucins. These proteins are characterized by
      poorly conserved repeated sequences that are rich in prolines and potentially
      glycosylated threonines and serines (PTS). We have now used the characteristics
      of the PTS repeat domain to identify Drosophila mucins in a simple bioinformatics
      approach. Searching the predicted protein database for proteins with at least 4
      repeats and a high ST content, more than 30 mucin-like proteins were identified,
      ranging from 300-23000 amino acids in length. We find that Drosophila mucins are
      present at all stages of the fly life cycle, and that their transcripts localize
      to selective organs analogous to sites of vertebrate mucin expression. The
      results could allow for addressing basic questions about human mucin-related
      diseases in this model system. Additionally, many of the mucins are expressed in
      selective tissues during embryogenesis, thus revealing new potential functions
      for mucins as apical matrix components during organ morphogenesis.

PMID- 18725943
TI  - Dynamical systems analysis of mitochondrial BAK activation kinetics predicts
      resistance to BH3 domains.
AB  - INTRODUCTION: The molecular mechanism underlying mitochondrial BAK activation
      during apoptosis remains highly controversial. Two seemingly conflicting models
      have been proposed. In one, BAK requires so-called activating BH3 only proteins
      (aBH3) to initiate its conformation change. In the other, displacement from
      inhibitory pro-survival BCL-2 proteins (PBPs) and monomerization of BAK by PBP
      selective dissociator BH3-only proteins (dBH3) is sufficient.
      METHODOLOGY/PRINCIPAL FINDINGS: To better understand the kinetic implications of
      these conflicting but highly evidence-based models, we have conducted a
      deterministic, dynamical systems analysis to explore the kinetics underlying the
      first step of BAK activation, as a non-linear reaction system. We show that dBH3
      induced BAK activation is efficient, even in the absence of aBH3s, provided
      constitutive interaction of PBPs with open conformation BAK occurs in an
      adenoviral E1B 19K-like manner. The pattern of PBP expression robustly predicts
      the efficacy of dBH3s. CONCLUSION: Our findings accommodate the prevailing BAK
      activation models as potentially coexisting mechanisms capable of initiating BAK
      activation, and supports a model based approach for predicting resistance to
      therapeutically relevant small molecule BH3 mimetics.

PMID- 18725944
TI  - Prefrontal norepinephrine determines attribution of "high" motivational salience.
AB  - Intense motivational salience attribution is considered to have a major role in
      the development of different psychopathologies. Numerous brain areas are involved
      in "normal" motivational salience attribution processes; however, it is not clear
      whether common or different neural mechanisms also underlie intense motivational
      salience attribution. To elucidate this a brain area and a neural system had to
      be envisaged that were involved only in motivational salience attribution to
      highly salient stimuli. Using intracerebral microdialysis, we found that natural
      stimuli induced an increase in norepinephrine release in the medial prefrontal
      cortex of mice proportional to their salience, and that selective prefrontal
      norepinephrine depletion abolished the increase of norepinephrine release in the
      medial prefrontal cortex induced by exposure to appetitive (palatable food) or
      aversive (light) stimuli independently of salience. However, selective
      norepinephrine depletion in the medial prefrontal cortex impaired the place
      conditioning induced exclusively by highly salient stimuli, thus indicating that
      prefrontal noradrenergic transmission determines approach or avoidance responses
      to both reward- and aversion-related natural stimuli only when the salience of
      the unconditioned natural stimulus is high enough to induce sustained
      norepinephrine outflow. This affirms that prefrontal noradrenergic transmission
      determines motivational salience attribution selectively when intense
      motivational salience is processed, as in conditions that characterize
      psychopathological outcomes.

PMID- 18725945
TI  - Falling towards forgetfulness: synaptic decay prevents spontaneous recovery of
      memory.
AB  - Long after a new language has been learned and forgotten, relearning a few words
      seems to trigger the recall of other words. This "free-lunch learning" (FLL)
      effect has been demonstrated both in humans and in neural network models.
      Specifically, previous work proved that linear networks that learn a set of
      associations, then partially forget them all, and finally relearn some of the
      associations, show improved performance on the remaining (i.e., nonrelearned)
      associations. Here, we prove that relearning forgotten associations decreases
      performance on nonrelearned associations; an effect we call negative free-lunch
      learning. The difference between free-lunch learning and the negative free-lunch
      learning presented here is due to the particular method used to induce
      forgetting. Specifically, if forgetting is induced by isotropic drifting of
      weight vectors (i.e., by adding isotropic noise), then free-lunch learning is
      observed. However, as proved here, if forgetting is induced by weight values that
      simply decay or fall towards zero, then negative free-lunch learning is observed.
      From a biological perspective, and assuming that nervous systems are analogous to
      the networks used here, this suggests that evolution may have selected
      physiological mechanisms that involve forgetting using a form of synaptic drift
      rather than synaptic decay, because synaptic drift, but not synaptic decay,
      yields free-lunch learning.

PMID- 18725946
TI  - Reverse and conventional chemical ecology approaches for the development of
      oviposition attractants for Culex mosquitoes.
AB  - Synthetic mosquito oviposition attractants are sorely needed for surveillance and
      control programs for Culex species, which are major vectors of pathogens causing
      various human diseases, including filariasis, encephalitis, and West Nile
      encephalomyelitis. We employed novel and conventional chemical ecology approaches
      to identify potential attractants, which were demonstrated in field tests to be
      effective for monitoring populations of Cx. p. quinquefasciatus in human
      dwellings. Immunohistochemistry studies showed that an odorant-binding protein
      from this species, CquiOBP1, is expressed in trichoid sensilla on the antennae,
      including short, sharp-tipped trichoid sensilla type, which house an olfactory
      receptor neuron sensitive to a previously identified mosquito oviposition
      pheromone (MOP), 6-acetoxy-5-hexadecanolide. CquiOBP1 exists in monomeric and
      dimeric forms. Monomeric CquiOBP1 bound MOP in a pH-dependent manner, with a
      change in secondary structure apparently related to the loss of binding at low
      pH. The pheromone antipode showed higher affinity than the natural stereoisomer.
      By using both CquiOBP1 as a molecular target in binding assays and gas
      chromatography-electroantennographic detection (GC-EAD), we identified nonanal,
      trimethylamine (TMA), and skatole as test compounds. Extensive field evaluations
      in Recife, Brazil, a region with high populations of Cx. p. quinquefasciatus,
      showed that a combination of TMA (0.9 microg/l) and nonanal (0.15 ng/microl) is
      equivalent in attraction to the currently used infusion-based lure, and superior
      in that the offensive smell of infusions was eliminated in the newly developed
      synthetic mixture.

PMID- 18725947
TI  - Induction of blood brain barrier tight junction protein alterations by CD8 T
      cells.
AB  - Disruption of the blood brain barrier (BBB) is a hallmark feature of immune
      mediated neurological disorders as diverse as viral hemorrhagic fevers, cerebral
      malaria and acute hemorrhagic leukoencephalitis. Although current models
      hypothesize that immune cells promote vascular permeability in human disease, the
      role CD8 T cells play in BBB breakdown remains poorly defined. Our laboratory has
      developed a novel murine model of CD8 T cell mediated central nervous system
      (CNS) vascular permeability using a variation of the Theiler's virus model of
      multiple sclerosis. In previous studies, we observed that MHC class II(-/-) (CD4
      T cell deficient), IFN-gammaR(-/-), TNF-alpha(-/-), TNFR1(-/-), TNFR2(-/-), and
      TNFR1/TNFR2 double knockout mice as well as those with inhibition of IL-1 and
      LTbeta activity were susceptible to CNS vascular permeability. Therefore, the
      objective of this study was to determine the extent immune effector proteins
      utilized by CD8 T cells, perforin and FasL, contributed to CNS vascular
      permeability. Using techniques such as fluorescent activated cell sorting (FACS),
      T1 gadolinium-enhanced magnetic resonance imaging (MRI), FITC-albumin leakage
      assays, microvessel isolation, western blotting and immunofluorescent microscopy,
      we show that in vivo stimulation of CNS infiltrating antigen-specific CD8 T cells
      initiates astrocyte activation, alteration of BBB tight junction proteins and
      increased CNS vascular permeability in a non-apoptotic manner. Using the
      aforementioned techniques, we found that despite having similar expansion of CD8
      T cells in the brain as wildtype and Fas Ligand deficient animals, perforin
      deficient mice were resistant to tight junction alterations and CNS vascular
      permeability. To our knowledge, this study is the first to demonstrate that CNS
      infiltrating antigen-specific CD8 T cells have the capacity to initiate BBB tight
      junction disruption through a non-apoptotic perforin dependent mechanism and our
      model is one of few that are useful for studies in this field. These novel
      findings are highly relevant to the development of therapies designed to control
      immune mediated CNS vascular permeability.

PMID- 18725948
TI  - A dominant X-linked QTL regulating pubertal timing in mice found by whole genome
      scanning and modified interval-specific congenic strain analysis.
AB  - BACKGROUND: Pubertal timing in mammals is triggered by reactivation of the
      hypothalamic-pituitary-gonadal (HPG) axis and modulated by both genetic and
      environmental factors. Strain-dependent differences in vaginal opening among
      inbred mouse strains suggest that genetic background contribute significantly to
      the puberty timing, although the exact mechanism remains unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: We performed a genome-wide scanning for linkage
      in reciprocal crosses between two strains, C3H/HeJ (C3H) and C57BL6/J (B6), which
      differed significantly in the pubertal timing. Vaginal opening (VO) was used to
      characterize pubertal timing in female mice, and the age at VO of all female mice
      (two parental strains, F1 and F2 progeny) was recorded. A genome-wide search was
      performed in 260 phenotypically extreme F2 mice out of 464 female progeny of the
      F1 intercrosses to identify quantitative trait loci (QTLs) controlling this
      trait. A QTL significantly associated was mapped to the DXMit166 marker (15.5 cM,
      LOD = 3.86, p<0.01) in the reciprocal cross population (C3HB6F2). This QTL
      contributed 2.1 days to the timing of VO, which accounted for 32.31% of the
      difference between the original strains. Further study showed that the QTL was B6
      dominant and explained 10.5% of variation to this trait with a power of 99.4% at
      an alpha level of 0.05.The location of the significant ChrX QTL found by genome
      scanning was then fine-mapped to a region of approximately 2.5 cM between marker
      DXMit68 and rs29053133 by generating and phenotyping a panel of 10 modified
      interval-specific congenic strains (mISCSs). CONCLUSIONS/SIGNIFICANCE: Such
      findings in our study lay a foundation for positional cloning of genes regulating
      the timing of puberty, and also reveal the fact that chromosome X (the sex
      chromosome) does carry gene(s) which take part in the regulative pathway of the
      pubertal timing in mice.

PMID- 18725949
TI  - HYAL1 and HYAL2 inhibit tumour growth in vivo but not in vitro.
AB  - BACKGROUND: We identified two 3p21.3 regions (LUCA and AP20) as most frequently
      affected in lung, breast and other carcinomas and reported their fine physical
      and gene maps. It is becoming increasingly clear that each of these two regions
      contains several TSGs. Until now TSGs which were isolated from AP20 and LUCA
      regions (e.g.G21/NPRL2, RASSF1A, RASSF1C, SEMA3B, SEMA3F, RBSP3) were shown to
      inhibit tumour cell growth both in vitro and in vivo. METHODOLOGY/PRINCIPAL
      FINDINGS: The effect of expression HYAL1 and HYAL2 was studied by colony
      formation inhibition, growth curve and cell proliferation tests in vitro and
      tumour growth assay in vivo. Very modest growth inhibition was detected in vitro
      in U2020 lung and KRC/Y renal carcinoma cell lines. In the in vivo experiment
      stably transfected KRC/Y cells expressing HYAL1 or HYAL2 were inoculated into
      SCID mice (10 and 12 mice respectively). Tumours grew in eight mice inoculated
      with HYAL1. Ectopic HYAL1 was deleted in all of them. HYAL2 was inoculated into
      12 mice and only four tumours were obtained. In 3 of them the gene was deleted.
      In one tumour it was present but not expressed. As expected for tumour suppressor
      genes HYAL1 and HYAL2 were down-expressed in 15 fresh lung squamous cell
      carcinomas (100%) and clear cell RCC tumours (60-67%). CONCLUSIONS/SIGNIFICANCE:
      The results suggest that the expression of either gene has led to inhibition of
      tumour growth in vivo without noticeable effect on growth in vitro. HYAL1 and
      HYAL2 thus differ in this aspect from other tumour suppressors like P53 or
      RASSF1A that inhibit growth both in vitro and in vivo. Targeting the
      microenvironment of cancer cells is one of the most promising venues of cancer
      therapeutics. As major hyaluronidases in human cells, HYAL1 and HYAL2 may control
      intercellular interactions and microenvironment of tumour cells providing
      excellent targets for cancer treatment.

PMID- 18725950
TI  - A feature-based approach to modeling protein-DNA interactions.
AB  - Transcription factor (TF) binding to its DNA target site is a fundamental
      regulatory interaction. The most common model used to represent TF binding
      specificities is a position specific scoring matrix (PSSM), which assumes
      independence between binding positions. However, in many cases, this simplifying
      assumption does not hold. Here, we present feature motif models (FMMs), a novel
      probabilistic method for modeling TF-DNA interactions, based on log-linear
      models. Our approach uses sequence features to represent TF binding
      specificities, where each feature may span multiple positions. We develop the
      mathematical formulation of our model and devise an algorithm for learning its
      structural features from binding site data. We also developed a discriminative
      motif finder, which discovers de novo FMMs that are enriched in target sets of
      sequences compared to background sets. We evaluate our approach on synthetic data
      and on the widely used TF chromatin immunoprecipitation (ChIP) dataset of
      Harbison et al. We then apply our algorithm to high-throughput TF ChIP data from
      mouse and human, reveal sequence features that are present in the binding
      specificities of mouse and human TFs, and show that FMMs explain TF binding
      significantly better than PSSMs. Our FMM learning and motif finder software are
      available at http://genie.weizmann.ac.il/.

PMID- 18725952
TI  - Case report: vancomycin-induced thrombocytopenia in a burn patient.
AB  - OBJECTIVE: Report an unusual cause of thrombocytopenia in a burn patient and
      provide a brief review of causes of thrombocytopenia in critically ill patients.
      METHODS: Case report format and selected review of PubMed search including the
      search terms thrombocytopenia, critical illness, and vancomycin. RESULTS: Reports
      of vancomycin-induced thrombocytopenia are uncommon. CONCLUSION: Drug-induced
      thrombocytopenia is a rare but important consideration in the evaluation of
      thrombocytopenia in critically ill patients. An increasing number of patients are
      treated with potentially causative agents including vancomycin and the diagnosis
      may be easily overlooked.

PMID- 18725951
TI  - Self containment, a property of modular RNA structures, distinguishes microRNAs.
AB  - RNA molecules will tend to adopt a folded conformation through the pairing of
      bases on a single strand; the resulting so-called secondary structure is critical
      to the function of many types of RNA. The secondary structure of a particular
      substring of functional RNA may depend on its surrounding sequence. Yet, some
      RNAs such as microRNAs retain their specific structures during biogenesis, which
      involves extraction of the substructure from a larger structural context, while
      other functional RNAs may be composed of a fusion of independent substructures.
      Such observations raise the question of whether particular functional RNA
      substructures may be selected for invariance of secondary structure to their
      surrounding nucleotide context. We define the property of self containment to be
      the tendency for an RNA sequence to robustly adopt the same optimal secondary
      structure regardless of whether it exists in isolation or is a substring of a
      longer sequence of arbitrary nucleotide content. We measured degree of self
      containment using a scoring method we call the self-containment index and found
      that miRNA stem loops exhibit high self containment, consistent with the
      requirement for structural invariance imposed by the miRNA biogenesis pathway,
      while most other structured RNAs do not. Further analysis revealed a trend toward
      higher self containment among clustered and conserved miRNAs, suggesting that
      high self containment may be a characteristic of novel miRNAs acquiring new
      genomic contexts. We found that miRNAs display significantly enhanced self
      containment compared to other functional RNAs, but we also found a trend toward
      natural selection for self containment in most functional RNA classes. We suggest
      that self containment arises out of selection for robustness against
      perturbations, invariance during biogenesis, and modular composition of
      structural function. Analysis of self containment will be important for both
      annotation and design of functional RNAs. A Python implementation and Web
      interface to calculate the self-containment index are available at
      http://kim.bio.upenn.edu/software/.

PMID- 18725953
TI  - The effect of magnetic fields on wound healing: experimental study and review of
      the literature.
AB  - OBJECTIVE: Magnets are purported to aid wound healing despite a paucity of
      scientific evidence. The purpose of this study was to evaluate the effect of
      static magnetic fields on cutaneous wound healing in an animal model. The
      literature was reviewed to explore the historical and scientific basis of magnet
      therapy and to define its current role in the evidence-based practice of plastic
      surgery. METHODS: Standardized wounds were created on the backs of 33 Sprague
      Dawley rats, which were divided into 3 groups with either a 23 gauss magnet
      (group 1), a sham magnet (group 2), or nothing (group 3) positioned over the
      wound. The rate of wound closure by secondary intention was compared between the
      groups. Literature review was conducted through searches of PubMed and Ovid
      databases for articles pertinent to magnets and wound healing. RESULTS: Wounds in
      the magnet group healed in an average of 15.3 days, significantly faster than
      those in either the sham group (20.9 days, P = .006) or control group (20.3 days,
      P < .0001). There was no statistically significant difference between the sham
      and control groups (P = .45). CONCLUSIONS: An externally applied, low-power,
      static magnetic field increases the rate of secondary healing. Review of the
      literature reveals conflicting evidence regarding the use of magnetic energy to
      aid the healing of bone, tendon, and skin. Level I studies are lacking and
      difficult to execute but are needed to define conclusively the role of magnets in
      clinical practice.

PMID- 18725954
TI  - Nodular fasciitis of the hand over the metacarpophalangeal joint: a case report.
AB  - OBJECTIVE: This study describes a case of nodular fasciitis involving the hand
      and reviews the neoplasm's pertinent clinical, histologic, and pathologic
      features. METHODS: The patient's chart, operative record, histologic specimens,
      and relevant literature were reviewed. RESULTS: We report a case of nodular
      fasciitis involving the hand of a 55-year-old woman that was treated with
      marginal excision. CONCLUSIONS: Nodular fasciitis is a self-limited, benign soft
      tissue tumor composed of fibroblasts and myofibroblasts that typically afflicts
      younger patients and rarely presents in the hand. Because of its presentation, it
      can be easily mistaken for a malignant neoplasm. However, most cases represent a
      reactive and therefore a polyclonal process. Marginal excision generally provides
      definitive treatment.

PMID- 18725955
TI  - Femtosecond laser nanoaxotomy properties and their effect on axonal recovery in
      C. elegans.
AB  - We present a study characterizing the properties of femtosecond laser nanosurgery
      applied to individual axons in live Caenorhabditis elegans (C. elegans) using
      nano-Joule laser pulses at 1 kHz repetition rate. Emphasis is placed on the
      characterization of the damage threshold, the extent of damage, and the
      statistical rates of axonal recovery as a function of laser parameters. The
      ablation threshold decreases with increasing number of pulses applied during
      nanoaxotomy. This dependency suggests the existence of an incubation effect. In
      terms of extent of damage, the energy per pulse is found to be a more critical
      parameter than the number of pulses. Axonal recovery improves when surgery is
      performed using a large number of low energy pulses.

PMID- 18725956
TI  - Neuropeptide receptor transcriptome reveals unidentified neuroendocrine pathways.
AB  - Neuropeptides are an important class of molecules involved in diverse aspects of
      metazoan development and homeostasis. Insects are ideal model systems to
      investigate neuropeptide functions, and the major focus of insect neuropeptide
      research in the last decade has been on the identification of their receptors.
      Despite these vigorous efforts, receptors for some key neuropeptides in insect
      development such as prothoracicotropic hormone, eclosion hormone and allatotropin
      (AT), remain undefined. In this paper, we report the comprehensive cloning of
      neuropeptide G protein-coupled receptors from the silkworm, Bombyx mori, and
      systematic analyses of their expression. Based on the expression patterns of
      orphan receptors, we identified the long-sought receptor for AT, which is thought
      to stimulate juvenile hormone biosynthesis in the corpora allata (CA).
      Surprisingly, however, the AT receptor was not highly expressed in the CA, but
      instead was predominantly transcribed in the corpora cardiaca (CC), an organ
      adjacent to the CA. Indeed, by using a reverse-physiological approach, we
      purified and characterized novel allatoregulatory peptides produced in AT
      receptor-expressing CC cells, which may indirectly mediate AT activity on the CA.
      All of the above findings confirm the effectiveness of a systematic analysis of
      the receptor transcriptome, not only in characterizing orphan receptors, but also
      in identifying novel players and hidden mechanisms in important biological
      processes. This work illustrates how using a combinatorial approach employing
      bioinformatic, molecular, biochemical and physiological methods can help solve
      recalcitrant problems in neuropeptide research.

PMID- 18725957
TI  - Bradykinin [corrected] B1 receptor antagonism is beneficial in renal ischemia
      reperfusion injury.
AB  - Previously we have demonstrated that bradykinin B1 receptor deficient mice (B1KO)
      were protected against renal ischemia and reperfusion injury (IRI). Here, we
      aimed to analyze the effect of B1 antagonism on renal IRI and to study whether
      B1R knockout or antagonism could modulate the renal expression of pro and anti
      inflammatory molecules. To this end, mice were subjected to 45 minutes ischemia
      and reperfused at 4, 24, 48 and 120 hours. Wild-type mice were treated intra
      peritoneally with antagonists of either B1 (R-954, 200 microg/kg) or B2 receptor
      (HOE140, 200 microg/kg) 30 minutes prior to ischemia. Blood samples were
      collected to ascertain serum creatinine level, and kidneys were harvested for
      gene transcript analyses by real-time PCR. Herein, B1R antagonism (R-954) was
      able to decrease serum creatinine levels, whereas B2R antagonism had no effect.
      The protection seen under B1R deletion or antagonism was associated with an
      increased expression of GATA-3, IL-4 and IL-10 and a decreased T-bet and IL-1beta
      transcription. Moreover, treatment with R-954 resulted in lower MCP-1, and higher
      HO-1 expression. Our results demonstrated that bradykinin B1R antagonism is
      beneficial in renal IRI.

PMID- 18725958
TI  - Quantifying data quality for clinical trials using electronic data capture.
AB  - BACKGROUND: Historically, only partial assessments of data quality have been
      performed in clinical trials, for which the most common method of measuring
      database error rates has been to compare the case report form (CRF) to database
      entries and count discrepancies. Importantly, errors arising from medical record
      abstraction and transcription are rarely evaluated as part of such quality
      assessments. Electronic Data Capture (EDC) technology has had a further impact,
      as paper CRFs typically leveraged for quality measurement are not used in EDC
      processes. METHODS AND PRINCIPAL FINDINGS: The National Institute on Drug Abuse
      Treatment Clinical Trials Network has developed, implemented, and evaluated
      methodology for holistically assessing data quality on EDC trials. We
      characterize the average source-to-database error rate (14.3 errors per 10,000
      fields) for the first year of use of the new evaluation method. This error rate
      was significantly lower than the average of published error rates for source-to
      database audits, and was similar to CRF-to-database error rates reported in the
      published literature. We attribute this largely to an absence of medical record
      abstraction on the trials we examined, and to an outpatient setting characterized
      by less acute patient conditions. CONCLUSIONS: Historically, medical record
      abstraction is the most significant source of error by an order of magnitude, and
      should be measured and managed during the course of clinical trials. Source-to
      database error rates are highly dependent on the amount of structured data
      collection in the clinical setting and on the complexity of the medical record,
      dependencies that should be considered when developing data quality benchmarks.

PMID- 18725959
TI  - The actin-binding protein capulet genetically interacts with the microtubule
      motor kinesin to maintain neuronal dendrite homeostasis.
AB  - BACKGROUND: Neurons require precise cytoskeletal regulation within neurites,
      containing microtubule tracks for cargo transport in axons and dendrites or
      within synapses containing organized actin. Due to the unique architecture and
      specialized function of neurons, neurons are particularly susceptible to
      perturbation of the cytoskeleton. Numerous actin-binding proteins help maintain
      proper cytoskeletal regulation. METHODOLOGY/PRINCIPAL FINDINGS: From a Drosophila
      forward genetic screen, we identified a mutation in capulet--encoding a conserved
      actin-binding protein--that causes abnormal aggregates of actin within dendrites.
      Through interaction studies, we demonstrate that simultaneous genetic
      inactivation of capulet and kinesin heavy chain, a microtubule motor protein,
      produces elongate cofilin-actin rods within dendrites but not axons. These rods
      resemble actin-rich structures induced in both mammalian neurodegenerative and
      Drosophila Alzheimer's models, but have not previously been identified by loss of
      function mutations in vivo. We further demonstrate that mitochondria, which are
      transported by Kinesin, have impaired distribution along dendrites in a capulet
      mutant. While Capulet and Cofilin may biochemically cooperate in certain
      circumstances, in neuronal dendrites they genetically antagonize each other.
      CONCLUSIONS/SIGNIFICANCE: The present study is the first molecularly defined loss
      of function demonstration of actin-cofilin rods in vivo. This study suggests that
      simultaneous, seemingly minor perturbations in neuronal dendrites can synergize
      producing severe abnormalities affecting actin, microtubules and
      mitochondria/energy availability in dendrites. Additionally, as >90% of
      Alzheimer's and Parkinson's cases are sporadic this study suggests mechanisms by
      which multiple mutations together may contribute to neurodegeneration instead of
      reliance on single mutations to produce disease.

PMID- 18725960
TI  - Tyrosine phosphorylation of the UDP-glucose dehydrogenase of Escherichia coli is
      at the crossroads of colanic acid synthesis and polymyxin resistance.
AB  - BACKGROUND: In recent years, an idiosyncratic new class of bacterial enzymes,
      named BY-kinases, has been shown to catalyze protein-tyrosine phosphorylation.
      These enzymes share no structural and functional similarities with their
      eukaryotic counterparts and, to date, only few substrates of BY-kinases have been
      characterized. BY-kinases have been shown to participate in various physiological
      processes. Nevertheless, we are at a very early stage of defining their
      importance in the bacterial cell. In Escherichia coli, two BY-kinases, Wzc and
      Etk, have been characterized biochemically. Wzc has been shown to phosphorylate
      the UDP-glucose dehydrogenase Ugd in vitro. Not only is Ugd involved in the
      biosynthesis of extracellular polysaccharides, but also in the production of UDP
      4-amino-4-deoxy-L-arabinose, a compound that renders E. coli resistant to
      cationic antimicrobial peptides. METHODOLOGY/PRINCIPAL FINDINGS: Here, we studied
      the role of Ugd phosphorylation. We first confirmed in vivo the phosphorylation
      of Ugd by Wzc and we demonstrated that Ugd is also phosphorylated by Etk, the
      other BY-kinase identified in E. coli. Tyrosine 71 (Tyr71) was characterized as
      the Ugd site phosphorylated by both Wzc and Etk. The regulatory role of Tyr71
      phosphorylation on Ugd activity was then assessed and Tyr71 mutation was found to
      prevent Ugd activation by phosphorylation. Further, Ugd phosphorylation by Wzc or
      Etk was shown to serve distinct physiological purposes. Phosphorylation of Ugd by
      Wzc was found to participate in the regulation of the amount of the
      exopolysaccharide colanic acid, whereas Etk-mediated Ugd phosphorylation appeared
      to participate in the resistance of E. coli to the antibiotic polymyxin.
      CONCLUSIONS/SIGNIFICANCE: Ugd phosphorylation seems to be at the junction between
      two distinct biosynthetic pathways, illustrating the regulatory potential of
      tyrosine phosphorylation in bacterial physiology.

PMID- 18725961
TI  - Risk factors for congenital cryptorchidism in a prospective birth cohort study.
AB  - BACKGROUND: Risk factors for congenital cryptorchidism were investigated in a
      prospective birth cohort study in Denmark and Finland from 1997 to 2001.
      METHODOLOGY AND PRINCIPAL FINDINGS: In total, 2,496 boys were examined for
      cryptorchidism at birth (cryptorchid/healthy: 128/2,368) and three months old
      (33/2,215). Information on risk factors was obtained antenatally
      (questionnaire/interview) or at birth from birth records. Use of nicotine
      substitutes during pregnancy (n = 40) and infertility treatment by intrauterine
      insemination (n = 49) were associated with an increased risk for cryptorchidism,
      adjusted odds ratio (95% confidence interval) (OR (95%CI)) 3.04 (95%CI 1.00-9.27)
      and 3.01 (95%CI 1.27-7.15), respectively. No association was seen for mothers (n
      = 79) who had infertility treatment in form of intracytoplasmic sperm injection
      (ICSI) or in vitro fertilization (IVF) treatment (OR 0.71 95%CI 0.21-2.38). In
      total, 728 (29%) reported to have smoked during pregnancy, however, no increased
      risk among maternal smokers was found. Furthermore, we found statistically
      significant associations between cryptorchidism and low birth weight,
      prematurity, being small for gestational age, substantial vaginal bleeding, and
      breech presentation, which are in accordance with other studies. CONCLUSIONS AND
      SIGNIFICANCE: Our study revealed two novel risk factors for cryptorchidism:
      intrauterine insemination and the use of nicotine substitutes in pregnancy. This
      suggests that cryptorchidism may not only be associated to genetic factors, but
      also to maternal lifestyle and exposure.

PMID- 18725962
TI  - Bioactive endophytes warrant intensified exploration and conservation.
AB  - BACKGROUND: A key argument in favor of conserving biodiversity is that as yet
      undiscovered biodiversity will yield products of great use to humans. However,
      the link between undiscovered biodiversity and useful products is largely
      conjectural. Here we provide direct evidence from bioassays of endophytes
      isolated from tropical plants and bioinformatic analyses that novel biology will
      indeed yield novel chemistry of potential value. METHODOLOGY/PRINCIPAL FINDINGS:
      We isolated and cultured 135 endophytic fungi and bacteria from plants collected
      in Peru. nrDNAs were compared to samples deposited in GenBank to ascertain the
      genetic novelty of cultured specimens. Ten endophytes were found to be as much as
      15-30% different than any sequence in GenBank. Phylogenetic trees, using the most
      similar sequences in GenBank, were constructed for each endophyte to measure
      phylogenetic distance. Assays were also conducted on each cultured endophyte to
      record bioactivity, of which 65 were found to be bioactive.
      CONCLUSIONS/SIGNIFICANCE: The novelty of our contribution is that we have
      combined bioinformatic analyses that document the diversity found in
      environmental samples with culturing and bioassays. These results highlight the
      hidden hyperdiversity of endophytic fungi and the urgent need to explore and
      conserve hidden microbial diversity. This study also showcases how undergraduate
      students can obtain data of great scientific significance.

PMID- 18725963
TI  - A Comparative Study of Galvanic Replacement Reactions Involving Ag Nanocubes and
      AuCl(2) or AuCl(4).

PMID- 18725964
TI  - Psychosocial Moderators the Effects of Transitioning Into Filial Caregiving on
      Mental and Physical Health.
AB  - A life-course theoretical perspective guided this study to examine how effects on
      mental and physical health (depressive symptoms, hostility, global happiness,
      self-esteem, personal mastery, psychological wellness, self-rated physical
      health) of transitioning into filial caregiving for a sole surviving parent are
      moderated by prior relationship quality, filial obligation, race or ethnicity,
      education, income, employment status, marital status, and parental status.
      Results from models estimated using longitudinal data from 1,060 adults aged 25
      to 65 years at baseline (National Survey of Families and Households, 1987 to
      1994) suggested that life-course and contextual factors do contribute to
      patterning health risks of caregiving, often in different ways for men and women:
      For example, low income puts daughter caregivers at greater risk for decline in
      physical health, combining employment with filial caregiving is more problematic
      for daughters' mental health, and being an unmarried filial caregiver is more
      problematic for men. Heterogeneity in the experience of filial care needs further
      attention in future research.

PMID- 18725965
TI  - Cerebral arterial gas embolism following cardiopulmonary bypass surgery.

PMID- 18725966
TI  - How is spatial context learning integrated over signal versus noise? A primacy
      effect in contextual cueing.
AB  - Over repeated exposure to particular visual search displays, subjects are able to
      implicitly extract regularities that then make search more efficient-a phenomenon
      known as contextual cueing. Here we explore how the learning involved in
      contextual cueing is formed, maintained, and updated over experience. During an
      initial training phase, a group of signal first subjects searched through a
      series of predictive displays (where distractor locations were perfectly
      correlated with the target location), followed with no overt break by a series of
      unpredictive displays (where repeated contexts were uncorrelated with target
      locations). A second noise first group of subjects encountered the unpredictive
      displays followed by the predictive displays. Despite the fact that both groups
      had the same overall exposure to signal and noise, only the signal first group
      demonstrated subsequent contextual cueing. This primacy effect indicates that
      initial experience can result in hypotheses about regularities in displays-or the
      lack thereof-which then become resistant to updating. The absence of regularities
      in early stages of training even blocked observers from learning predictive
      regularities later on.

PMID- 18725967
TI  - MPW1K Performs Much Better than B3LYP in DFT Calculations on Reactions that
      Proceed by Proton-Coupled Electron Transfer (PCET).
AB  - DFT calculations have been performed with the B3LYP and MPW1K functional on the
      hydrogen atom abstraction reactions of ethenoxyl with ethenol and of phenoxyl
      with both phenol and alpha-naphthol. Comparison with the results of G3
      calculations shows that B3LYP seriously underestimates the barrier heights for
      the reaction of ethenoxyl with ethenol by both proton-coupled electron transfer
      (PCET) and hydrogen atom transfer (HAT) mechanisms. The MPW1K functional also
      underestimates the barrier heights, but by much less than B3LYP. Similarly,
      comparison with the results of experiments on the reaction of phenoxyl radical
      with alpha-naphthol indicates that the barrier height for the preferred PCET
      mechanism is calculated more accurately by MPW1K than by B3LYP. These findings
      indicate that the MPW1K functional is much better suited than B3LYP for
      calculations on hydrogen abstraction reactions by both HAT and PCET mechanisms.

PMID- 18725968
TI  - Non-Redox Assisted Oxygen-Oxygen Bond Homolysis in Titanocene Alkylperoxide
      Complexes: [Cp(2)Ti(eta-OOBu)L], L = Cl, OTf, Br, OEt(2), Et(3)P.
AB  - The titanium(IV) alkylperoxide complex Cp(2)Ti(OO(t)Bu)Cl (1) is formed on
      treatment of Cp(2)TiCl(2) with NaOO(t)Bu in THF at -20 degrees C. Treatment of 1
      with AgOTf at -20 degrees C gives the triflate complex Cp(2)Ti(OO(t)Bu)OTf (2),
      which is rapidly converted to the bromide Cp(2)Ti(OO(t)Bu)Br (3) on addition of
      (n)Bu(4)NBr. The X-ray crystal structures of 1 and 3 both show eta(1)-OO(t)Bu
      ligands. Complex 2 is stable only below -20 degrees C; (1)H, (13)C, and (19)F NMR
      spectra suggest that it also contains an eta(1)-OO(t)Bu ligand. Removal of the
      chloride from 1 with [Ag(Et(2)O)(2)]BAr'(4) (Ar' = 3,5-(CF(3))(2)C(6)H(3)))
      yields the etherate complex [Cp(2)Ti(OO(t)Bu)(OEt(2))]BAr'(4) (4). Again,
      coordination of a fourth ligand to the Ti center indicates an eta(1)-OO(t)Bu
      ligand in 4. These peroxide complexes do not directly oxidize olefins or
      phosphines. For instance, the cationic etherate complex 4 reacts with excess
      Et(3)P simply by displacement of the ether to form [Cp(2)Ti(eta(1)
      OO(t)Bu)(Et(3)P)]BAr'(4) (5). Compounds 1-5 all decompose by O-O bond homolysis,
      based on trapping and computational studies. The lack of direct oxygen atom
      transfer reactivity is likely due to the eta(1) coordination of the peroxide and
      the inability to adopt more reactive eta(2) geometry. DFT calculations indicate
      that the steric bulk of the (t)Bu group inhibits formation of the hypothetical
      [Cp(2)Ti(eta(2)-OO(t)Bu)](+) species.

PMID- 18725969
TI  - Transgene-induced gene silencing is not affected by a change in ploidy level.
AB  - BACKGROUND: Whole genome duplication, which results in polyploidy, is a common
      feature of plant populations and a recurring event in the evolution of flowering
      plants. Polyploidy can result in changes to gene expression and epigenetic
      instability. Several epigenetic phenomena, occurring at the transcriptional or
      post-transcriptional level, have been documented in allopolyploids (polyploids
      derived from species hybrids) of Arabidopsis thaliana, yet findings in
      autopolyploids (polyploids derived from the duplication of the genome of a single
      species) are limited. Here, we tested the hypothesis that an increase in ploidy
      enhances transgene-induced post-transcriptional gene silencing using
      autopolyploids of A. thaliana. METHODOLOGY/PRINCIPAL FINDINGS: Diploid and
      tetraploid individuals of four independent homozygous transgenic lines of A.
      thaliana transformed with chalcone synthase (CHS) inverted repeat (hairpin)
      constructs were generated. For each line diploids and tetraploids were compared
      for efficiency in post-transcriptional silencing of the endogenous CHS gene. The
      four lines differed substantially in their silencing efficiency. Yet, diploid and
      tetraploid plants derived from these plants and containing therefore identical
      transgene insertions showed no difference in the efficiency silencing CHS as
      assayed by visual scoring, anthocyanin assays and quantification of CHS mRNA.
      CONCLUSIONS/SIGNIFICANCE: Our results in A. thaliana indicated that there is no
      effect of ploidy level on transgene-induced post-transcriptional gene silencing.
      Our findings that post-transcriptional mechanisms were equally effective in
      diploids and tetraploids supports the use of transgene-driven post
      transcriptional gene silencing as a useful mechanism to modify gene expression in
      polyploid species.

PMID- 18725970
TI  - Microbial prevalence, diversity and abundance in amniotic fluid during preterm
      labor: a molecular and culture-based investigation.
AB  - BACKGROUND: Preterm delivery causes substantial neonatal mortality and morbidity.
      Unrecognized intra-amniotic infections caused by cultivation-resistant microbes
      may play a role. Molecular methods can detect, characterize and quantify microbes
      independently of traditional culture techniques. However, molecular studies that
      define the diversity and abundance of microbes invading the amniotic cavity, and
      evaluate their clinical significance within a causal framework, are lacking.
      METHODS AND FINDINGS: In parallel with culture, we used broad-range end-point and
      real-time PCR assays to amplify, identify and quantify ribosomal DNA (rDNA) of
      bacteria, fungi and archaea from amniotic fluid of 166 women in preterm labor
      with intact membranes. We sequenced up to 24 rRNA clones per positive specimen
      and assigned taxonomic designations to approximately the species level. Microbial
      prevalence, diversity and abundance were correlated with host inflammation and
      with gestational and neonatal outcomes. Study subjects who delivered at term
      served as controls. The combined use of molecular and culture methods revealed a
      greater prevalence (15% of subjects) and diversity (18 taxa) of microbes in
      amniotic fluid than did culture alone (9.6% of subjects; 11 taxa). The taxa
      detected only by PCR included a related group of fastidious bacteria, comprised
      of Sneathia sanguinegens, Leptotrichia amnionii and an unassigned, uncultivated,
      and previously-uncharacterized bacterium; one or more members of this group were
      detected in 25% of positive specimens. A positive PCR was associated with
      histologic chorioamnionitis (adjusted odds ratio [OR] 20; 95% CI, 2.4 to 172),
      and funisitis (adjusted OR 18; 95% CI, 3.1 to 99). The positive predictive value
      of PCR for preterm delivery was 100 percent. A temporal association between a
      positive PCR and delivery was supported by a shortened amniocentesis-to-delivery
      interval (adjusted hazard ratio 4.6; 95% CI, 2.2 to 9.5). A dose-response
      association was demonstrated between bacterial rDNA abundance and gestational age
      at delivery (r(2) = 0.42; P<0.002). CONCLUSIONS: The amniotic cavity of women in
      preterm labor harbors DNA from a greater diversity of microbes than previously
      suspected, including as-yet uncultivated, previously-uncharacterized taxa. The
      strength, temporality and gradient with which these microbial sequence types are
      associated with preterm delivery support a causal relationship.

PMID- 18725971
TI  - The critical role of partially exposed N-terminal valine residue in stabilizing
      GH10 xylanase from Bacillus sp.NG-27 under poly-extreme conditions.
AB  - BACKGROUND: Understanding the mechanisms that govern protein stability under poly
      extreme conditions continues to be a major challenge. Xylanase (BSX) from
      Bacillus sp. NG-27, which has a TIM-barrel structure, shows optimum activity at
      high temperature and alkaline pH, and is resistant to denaturation by SDS and
      degradation by proteinase K. A comparative circular dichroism analysis was
      performed on native BSX and a recombinant BSX (R-BSX) with just one additional
      methionine resulting from the start codon. The results of this analysis revealed
      the role of the partially exposed N-terminus in the unfolding of BSX in response
      to an increase in temperature. METHODOLOGY: We investigated the poly
      extremophilicity of BSX to deduce the structural features responsible for its
      stability under one set of conditions, in order to gain information about its
      stability in other extreme conditions. To systematically address the role of the
      partially exposed N-terminus in BSX stability, a series of mutants was generated
      in which the first hydrophobic residue, valine (Val1), was either deleted or
      substituted with various amino acids. Each mutant was subsequently analyzed for
      its thermal, SDS and proteinase K stability in comparison to native BSX.
      CONCLUSIONS: A single conversion of Val1 to glycine (Gly) changed R-BSX from
      being thermo- and alkali- stable and proteinase K and SDS resistant, to being
      thermolabile and proteinase K-, alkali- and SDS- sensitive. This result provided
      insight into the structure-function relationships of BSX under poly-extreme
      conditions. Molecular, biochemical and structural data revealed that the poly
      extremophilicity of BSX is governed by a partially exposed N-terminus through
      hydrophobic interactions. Such hitherto unidentified N-terminal hydrophobic
      interactions may play a similar role in other proteins, especially those with TIM
      barrel structures. The results of the present study are therefore of major
      significance for protein folding and protein engineering.

PMID- 18725972
TI  - Individual differences in the amount and timing of salivary melatonin secretion.
AB  - The aim of this study was to examine individual differences in a large sample of
      complete melatonin profiles not suppressed by light and search for possible
      associations between the amount and timing of melatonin secretion and a multitude
      of lifestyle variables. The melatonin profiles were derived from saliva samples
      collected every 30 minutes in dim light from 85 healthy women and 85 healthy men
      aged 18-45 years. There was a large individual variability in the amount of
      melatonin secreted with peak values ranging from 2 to 84 pg/ml. The onset of
      melatonin secretion ranged from 18:13 to 00:26 hours. The use of hormonal birth
      control, reduced levels of employment, a smaller number of days on a fixed sleep
      schedule, increased day length and lower weight were associated with an increased
      amplitude of melatonin secretion. The use of hormonal birth control, contact
      lenses, a younger age, and lower ratings of mania and paranoia were associated
      with a longer duration of melatonin secretion. An earlier occurrence of the onset
      of melatonin secretion was associated with an earlier wake time, more morningness
      and the absence of a bed partner. Lifestyle and behavioral variables were only
      able to explain about 15% of the individual variability in the amount of
      melatonin secretion, which is likely because of a substantial genetic influence
      on the levels of melatonin secretion.

PMID- 18725974
TI  - Breast tumor cells with PI3K mutation or HER2 amplification are selectively
      addicted to Akt signaling.
AB  - BACKGROUND: Dysregulated PI3K/Akt signaling occurs commonly in breast cancers and
      is due to HER2 amplification, PI3K mutation or PTEN inactivation. The objective
      of this study was to determine the role of Akt activation in breast cancer as a
      function of mechanism of activation and whether inhibition of Akt signaling is a
      feasible approach to therapy. METHODOLOGY/PRINCIPAL FINDINGS: A selective
      allosteric inhibitor of Akt kinase was used to interrogate a panel of breast
      cancer cell lines characterized for genetic lesions that activate PI3K/Akt
      signaling: HER2 amplification or PI3K or PTEN mutations in order to determine the
      biochemical and biologic consequences of inhibition of this pathway. A variety of
      molecular techniques and tissue culture and in vivo xenograft models revealed
      that tumors with mutational activation of Akt signaling were selectively
      dependent on the pathway. In sensitive cells, pathway inhibition resulted in D
      cyclin loss, G1 arrest and induction of apoptosis, whereas cells without pathway
      activation were unaffected. Most importantly, the drug effectively inhibited Akt
      kinase and its downstream effectors in vivo and caused complete suppression of
      the growth of breast cancer xenografts with PI3K mutation or HER2 amplification,
      including models of the latter selected for resistance to Herceptin. Furthermore,
      chronic administration of the drug was well-tolerated, causing only transient
      hyperglycemia without gross toxicity to the host despite the pleiotropic normal
      functions of Akt. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that breast
      cancers with PI3K mutation or HER2 amplification are selectively dependent on Akt
      signaling, and that effective inhibition of Akt in tumors is feasible and
      effective in vivo. These findings suggest that direct inhibition of Akt may
      represent a therapeutic strategy for breast and other cancers that are addicted
      to the pathway including tumors with resistant to Herceptin.

PMID- 18725975
TI  - Genetic variability of hepatitis C virus before and after combined therapy of
      interferon plus ribavirin.
AB  - We present an analysis of the selective forces acting on two hepatitis C virus
      genome regions previously postulated to be involved in the viral response to
      combined antiviral therapy. One includes the three hypervariable regions in the
      envelope E2 glycoprotein, and the other encompasses the PKR binding domain and
      the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients
      to combined therapy (interferon alpha-2a plus ribavirin) for which samples were
      obtained before initiation of therapy and after 6 or/and 12 months of treatment.
      A range of 25-100 clones per patient, genome region and time sample were
      sequenced. These were used to detect general patterns of adaptation, to identify
      particular adaptation mechanisms and to analyze the patterns of evolutionary
      change in both genome regions. These analyses failed to detect a common adaptive
      mechanism for the lack of response to antiviral treatment in these patients. On
      the contrary, a wide range of situations were observed, from patients showing no
      positively selected sites to others with many, and with completely different
      topologies in the reconstructed phylogenetic trees. Altogether, these results
      suggest that viral strategies to evade selection pressure from the immune system
      and antiviral therapies do not result from a single mechanism and they are likely
      based on a range of different alternatives, in which several different changes,
      or their combination, along the HCV genome confer viruses the ability to overcome
      strong selective pressures.

PMID- 18725976
TI  - Cre-dependent expression of multiple transgenes in isolated neurons of the adult
      forebrain.
AB  - BACKGROUND: Transgenic mice with mosaic, Golgi-staining-like expression of
      enhanced green fluorescent protein (EGFP) have been very useful in studying the
      dynamics of neuronal structure and function. In order to further investigate the
      molecular events regulating structural plasticity, it would be useful to express
      multiple proteins in the same sparse neurons, allowing co-expression of
      functional proteins or co-labeling of subcellular compartments with other
      fluorescent proteins. However, it has been difficult to obtain reproducible
      expression in the same subset of neurons for direct comparison of neurons
      expressing different functional proteins. PRINCIPAL FINDINGS: Here we describe a
      Cre-transgenic line that allows reproducible expression of transgenic proteins of
      choice in a small number of neurons of the adult cortex, hippocampus, striatum,
      olfactory bulb, subiculum, hypothalamus, superior colliculus and amygdala. We
      show that using these Cre-transgenic mice, multiple Cre-dependent transgenes can
      be expressed together in the same isolated neurons. We also describe a Cre
      dependent transgenic line expressing a membrane associated EGFP (EGFP-F). Crossed
      with the Cre-transgenic line, EGFP-F expression starts in the adolescent
      forebrain, is present in dendrites, dendritic protrusions, axons and boutons and
      is strong enough for acute or chronic in vivo imaging. SIGNIFICANCE: This triple
      transgenic approach will aid the morphological and functional characterization of
      neurons in various Cre-dependent transgenic mice.

PMID- 18725977
TI  - Estimating receptive fields from responses to natural stimuli with asymmetric
      intensity distributions.
AB  - The reasons for using natural stimuli to study sensory function are quickly
      mounting, as recent studies have revealed important differences in neural
      responses to natural and artificial stimuli. However, natural stimuli typically
      contain strong correlations and are spherically asymmetric (i.e. stimulus
      intensities are not symmetrically distributed around the mean), and these
      statistical complexities can bias receptive field (RF) estimates when standard
      techniques such as spike-triggered averaging or reverse correlation are used.
      While a number of approaches have been developed to explicitly correct the bias
      due to stimulus correlations, there is no complementary technique to correct the
      bias due to stimulus asymmetries. Here, we develop a method for RF estimation
      that corrects reverse correlation RF estimates for the spherical asymmetries
      present in natural stimuli. Using simulated neural responses, we demonstrate how
      stimulus asymmetries can bias reverse-correlation RF estimates (even for
      uncorrelated stimuli) and illustrate how this bias can be removed by explicit
      correction. We demonstrate the utility of the asymmetry correction method under
      experimental conditions by estimating RFs from the responses of retinal ganglion
      cells to natural stimuli and using these RFs to predict responses to novel
      stimuli.

PMID- 18725973
TI  - Predominant role of host genetics in controlling the composition of gut
      microbiota.
AB  - BACKGROUND: The human gastrointestinal tract is inhabited by a very diverse
      symbiotic microbiota, the composition of which depends on host genetics and the
      environment. Several studies suggested that the host genetics may influence the
      composition of gut microbiota but no genes involved in host control were
      proposed. We investigated the effects of the wild type and mutated alleles of the
      gene, which encodes the protein called pyrin, one of the regulators of innate
      immunity, on the composition of gut commensal bacteria. Mutations in MEFV lead to
      the autoinflammatory disorder, familial Mediterranean fever (FMF, MIM249100),
      which is characterized by recurrent self-resolving attacks of fever and
      polyserositis, with no clinical signs of disease in remission.
      METHODOLOGY/PRINCIPAL FINDINGS: A total of 19 FMF patients and eight healthy
      individuals were genotyped for mutations in the MEFV gene and gut bacterial
      diversity was assessed by sequencing 16S rRNA gene libraries and FISH analysis.
      These analyses demonstrated significant changes in bacterial community structure
      in FMF characterized by depletion of total numbers of bacteria, loss of
      diversity, and major shifts in bacterial populations within the Bacteroidetes,
      Firmicutes and Proteobacteria phyla in attack. In remission with no clinical
      signs of disease, bacterial diversity values were comparable with control but
      still, the bacterial composition was substantially deviant from the norm.
      Discriminant function analyses of gut bacterial diversity revealed highly
      specific, well-separated and distinct grouping, which depended on the allele
      carrier status of the host. CONCLUSIONS/SIGNIFICANCE: This is the first report
      that clearly establishes the link between the host genotype and the corresponding
      shifts in the gut microbiota (the latter confirmed by two independent
      techniques). It suggests that the host genetics is a key factor in host-microbe
      interaction determining a specific profile of commensal microbiota in the human
      gut.

PMID- 18725978
TI  - CHEK2 mutations affecting kinase activity together with mutations in TP53
      indicate a functional pathway associated with resistance to epirubicin in primary
      breast cancer.
AB  - BACKGROUND: Chemoresistance is the main obstacle to cure in most malignant
      diseases. Anthracyclines are among the main drugs used for breast cancer therapy
      and in many other malignant conditions. Single parameter analysis or global gene
      expression profiles have failed to identify mechanisms causing in vivo resistance
      to anthracyclines. While we previously found TP53 mutations in the L2/L3 domains
      to be associated with drug resistance, some tumors harboring wild-type TP53 were
      also therapy resistant. The aim of this study was; 1) To explore alterations in
      the TP53 gene with respect to resistance to a regular dose epirubicin regimen (90
      mg/m(2) every 3 week) in patients with primary, locally advanced breast cancer;
      2) Identify critical mechanisms activating p53 in response to DNA damage in
      breast cancer; 3) Evaluate in vitro function of Chk2 and p14 proteins
      corresponding to identified mutations in the CHEK2 and p14((ARF)) genes; and 4)
      Explore potential CHEK2 or p14((ARF)) germline mutations with respect to family
      cancer incidence. METHODS AND FINDINGS: Snap-frozen biopsies from 109 patients
      collected prior to epirubicin (as preoperative therapy were investigated for
      TP53, CHEK2 and p14((ARF)) mutations by sequencing the coding region and
      p14((ARF)) promoter methylations. TP53 mutations were associated with
      chemoresistance, defined as progressive disease on therapy (p = 0.0358; p =
      0.0136 for mutations affecting p53 loop domains L2/L3). Germline CHEK2 mutations
      (n = 3) were associated with therapy resistance (p = 0.0226). Combined, mutations
      affecting either CHEK2 or TP53 strongly predicted therapy resistance (p = 0.0101;
      TP53 mutations restricted to the L2/L3 domains: p = 0.0032). Two patients
      progressing on therapy harbored the CHEK2 mutation, Arg95Ter, completely
      abrogating Chk2 protein dimerization and kinase activity. One patient (Epi132)
      revealed family cancer occurrence resembling families harboring CHEK2 mutations
      in general, the other patient (epi203) was non-conclusive. No mutation or
      promoter hypermethylation in p14((ARF)) were detected. CONCLUSION: This study is
      the first reporting an association between CHEK2 mutations and therapy resistance
      in human cancers and to document mutations in two genes acting direct up/down
      stream to each other to cause therapy failure, emphasizing the need to
      investigate functional cascades in future studies.

PMID- 18725979
TI  - Virulence in murine model shows the existence of two distinct populations of
      Brazilian Vaccinia virus strains.
AB  - Brazilian Vaccinia virus had been isolated from sentinel mice, rodents and
      recently from humans, cows and calves during outbreaks on dairy farms in several
      rural areas in Brazil, leading to high economic and social impact. Some
      phylogenetic studies have demonstrated the existence of two different populations
      of Brazilian Vaccinia virus strains circulating in nature, but little is known
      about their biological characteristics. Therefore, our goal was to study the
      virulence pattern of seven Brazilian Vaccinia virus strains. Infected BALB/c mice
      were monitored for morbidity, mortality and viral replication in organs as
      trachea, lungs, heart, kidneys, liver, brain and spleen. Based on the virulence
      potential, the Brazilian Vaccinia virus strains were grouped into two groups. One
      group contained GP1V, VBH, SAV and BAV which caused disease and death in infected
      mice and the second one included ARAV, GP2V and PSTV which did not cause any
      clinical signals or death in infected BALB/c mice. The subdivision of Brazilian
      Vaccinia virus strains into two groups is in agreement with previous genetic
      studies. Those data reinforce the existence of different populations circulating
      in Brazil regarding the genetic and virulence characteristics.

PMID- 18725980
TI  - Seroprevalence and risk factors of chikungunya virus infection in Mayotte, Indian
      Ocean, 2005-2006: a population-based survey.
AB  - BACKGROUND: Since 2006, Chikungunya virus (CHIKV) has re-emerged as an important
      pathogen of global concern. However, individual and household factors associated
      with the acquisition and the magnitude of clinically silent CHIKV infections
      remain poorly understood. In this present study, we aimed to investigate the
      seroprevalence, estimate the proportion of symptomatic illness and identify the
      risk factors for CHIKV infection in the primo-exposed population of Mayotte.
      METHODS/ PRINCIPAL FINDINGS: We conducted a household-based cross sectional
      serosurvey in Mayotte in November and December 2006 using complex multistage
      cluster sampling. To produce the results representative of the island population
      aged 2 years or older, sample data were adjusted with sample weights. Explanatory
      and multiple logistic regression analyses were performed to investigate
      associations between CHIKV infection seropositivity (presence of IgM and/or IgG
      to CHIKV by enzyme-linked immunoabsorbent assay) and risk factors. A total of
      1154 individuals were analyzed. The overall seroprevalence of CHIKV infection was
      37.2% (95% CI = 33.9-40.5), 318 (72.3%) of the seropositive participants reported
      symptoms consistent with a CHIKV infection during the epidemic period. Risk
      factors for CHIKV seropositivity among adults (aged 15 years and older) were male
      gender, low socioeconomic index, schooling < or = 6 years and living in makeshift
      housing. CONCLUSIONS: Our findings indicate that roughly one out of four CHIKV
      infections is asymptomatic. Conditions associated with poverty may be considered
      as critical in CHIKV acquisition. Thus, these conditions should be taken into
      account in the development of future prevention strategies of CHIKV disease.

PMID- 18725981
TI  - Bad seeds produce bad crops: a single stage-process of prostate tumor invasion.
AB  - It is a commonly held belief that prostate carcinogenesis is a multi-stage
      process and that tumor invasion is triggered by the overproduction of proteolytic
      enzymes. This belief is consistent with data from cell cultures and animal
      models, whereas is hard to interpret several critical facts, including the
      presence of cancer in "healthy" young men and cancer DNA phenotype in
      morphologically normal prostate tissues. These facts argue that alternative
      pathways may exist for prostate tumor invasion in some cases. Since degradation
      of the basal cell layer is the most distinct sign of invasion, our recent studies
      have attempted to identify pre-invasive lesions with focal basal cell layer
      alterations. Our studies revealed that about 30% of prostate cancer patients
      harbored normal appearing duct or acinar clusters with a high frequency of focal
      basal cell layer disruptions. These focally disrupted basal cell layers had
      significantly reduced cell proliferation and tumor suppressor expression, whereas
      significantly elevated degeneration, apoptosis, and infiltration of
      immunoreactive cells. In sharp contrast, associated epithelial cell had
      significantly elevated proliferation, expression of malignancy-signature markers,
      and physical continuity with invasive lesions. Based on these and other findings,
      we have proposed that these normal appearing duct or acinar clusters are derived
      from monoclonal proliferation of genetically damaged stem cells and could
      progress directly to invasion through two pathways: 1) clonal in situ
      transformation (CIST) and 2) multi-potential progenitor mediated "budding"
      (MPMB). These pathways may contribute to early onset of prostate cancer at young
      ages, and to clinically more aggressive prostate tumors.

PMID- 18725982
TI  - Peroxisome Proliferator-Activated Receptors (PPARs) as Potential Inducers of
      Antineoplastic Effects in CNS Tumors.
AB  - The peroxisome proliferator-activated receptors (PPARs) are ligand-inducible
      transcription factors which belong to the superfamily of nuclear hormone
      receptors. In recent years it turned out that natural as well as synthetic PPAR
      agonists exhibit profound antineoplastic as well as redifferentiation effects in
      tumors of the central nervous system (CNS). The molecular understanding of the
      underlying mechanisms is still emerging, with partially controverse findings
      reported by a number of studies dealing with the influence of PPARs on treatment
      of tumor cells in vitro. Remarkably, studies examining the effects of these drugs
      in vivo are just beginning to emerge. However, the agonists of PPARs, in
      particular the thiazolidinediones, seem to be promising candidates for new
      approaches in human CNS tumor therapy.

PMID- 18725983
TI  - PPARalpha Ligands as Antitumorigenic and Antiangiogenic Agents.
AB  - Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear
      receptor family of ligand-activated transcription factors. This subfamily is
      composed of three members-PPARalpha, PPARdelta, and PPARgamma-that differ in
      their cell and tissue distribution as well as in their target genes. PPARalpha is
      abundantly expressed in liver, brown adipose tissue, kidney, intestine, heart,
      and skeletal muscle; and its ligands have been used to treat diseases such as
      obesity and diabetes. The recent finding that members of the PPAR family,
      including the PPARalpha, are expressed by tumor and endothelial cells together
      with the observation that PPAR ligands regulate cell growth, survival, migration,
      and invasion, suggested that PPARs also play a role in cancer. In this review, we
      focus on the contribution of PPARalpha to tumor and endothelial cell functions
      and provide compelling evidence that PPARalpha can be viewed as a new class of
      ligand activated tumor "suppressor" gene with antiangiogenic and antitumorigenic
      activities. Given that PPAR ligands are currently used in medicine as
      hypolipidemic drugs with excellent tolerance and limited toxicity, PPARalpha
      activation might offer a novel and potentially low-toxic approach for the
      treatment of tumor-associated angiogenesis and cancer.

PMID- 18725984
TI  - Laparoscopic extravesical ureteral reimplantation: technique.
AB  - Laparoscopic extravesical ureteral reimplantation in children is currently a
      technically demanding procedure with sparse literature to aid in mastering the
      learning curve. We present our most recent technique and lessons learned after 20
      cases in children 4-15 years of age. The literature is also reviewed to
      encapsulate the current state-of-the-art.

PMID- 18725985
TI  - Chondrosarcoma and peroxisome proliferator-activated receptor.
AB  - Induction of differentiation and apoptosis in cancer cells by ligands of
      PPARgamma is a novel therapeutic approach to malignant tumors. Chondrosarcoma
      (malignant cartilage tumor) and OUMS-27 cells (cell line established from grade
      III human chondrosarcoma) express PPARgamma. PPARgamma ligands inhibited cell
      proliferation in a dose-dependent manner, and induced apoptosis of OUMS-27. The
      higher-grade chondrosarcoma expressed a higher amount of antiapoptotic Bcl-xL in
      vivo. The treatment of OUMS-27 by 15d-PGJ(2), the most potent endogenous ligand
      for PPARgamma, downregulated expression of Bcl-xL and induced transient
      upregulation of proapoptotic Bax, which could accelerate cytochrome c release
      from mitochondria to the cytosol, followed by induction of caspase-dependent
      apoptosis. 15d-PGJ(2) induced the expression of CDK inhibitor p21 protein in
      human chondrosarcoma cells, which appears to be involved in the mechanism of
      inhibition of cell proliferation. These findings suggest that targeted therapy
      with PPARgamma ligands could be a novel strategy against chondrosarcoma.

PMID- 18725986
TI  - Technique of intravesical laparoscopy for ureteric reimplantation to treat VUR.
AB  - The prevalence of vesicoureteral reflux (VUR) has been estimated as 0.4 to 1.8%
      among the pediatric population. In children with urinary tract infection, the
      prevalence is typically from 30-50% with higher incidence occurring in infancy.
      When correction of VUR is determined to be necessary, traditionally open ureteral
      reimplantation by a variety of techniques has been the mainstay of treatment.
      This approach is justified because surgical correction affords a very high
      success rate of 99% in experienced hands and a low complication rate. In that
      context the purpose of presenting our surgical technique: laparoscopic
      intravesical ureteric reimplantation is to highlight the use of laparoscopy to
      perform ureteric reimplantation for the management of pediatric VUR.

PMID- 18725987
TI  - TreeGenes: A forest tree genome database.
AB  - The Dendrome Project and associated TreeGenes database serve the forest genetics
      research community through a curated and integrated web-based relational
      database. The research community is composed of approximately 2 000 members
      representing over 730 organizations worldwide. The database itself is composed of
      a wide range of genetic data from many forest trees with focused efforts on
      commercially important members of the Pinaceae family. The primary data types
      curated include species, publications, tree and DNA extraction information,
      genetic maps, molecular markers, ESTs, genotypic, and phenotypic data. There are
      currently ten main search modules or user access points within this PostgreSQL
      database. These access points allow users to navigate logically through the
      related data types. The goals of the Dendrome Project are to (1) provide a
      comprehensive resource for forest tree genomics data to facilitate gene discovery
      in related species, (2) develop interfaces that encourage the submission and
      integration of all genomic data, and to (3) centralize and distribute existing
      and novel online tools for the research community that both support and ease
      analysis. Recent developments have focused on increasing data content, functional
      annotations, data retrieval, and visualization tools. TreeGenes was developed to
      provide a centralized web resource with analysis and visualization tools to
      support data storage and exchange.

PMID- 18725988
TI  - Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent
      feedback loop in human cancer.
AB  - Numerous studies have established a causal link between aberrant mammalian target
      of rapamycin (mTOR) activation and tumorigenesis, indicating that mTOR inhibition
      may have therapeutic potential. In this study, we show that rapamycin and its
      analogs activate the MAPK pathway in human cancer, in what represents a novel
      mTORC1-MAPK feedback loop. We found that tumor samples from patients with biopsy
      accessible solid tumors of advanced disease treated with RAD001, a rapamycin
      derivative, showed an administration schedule-dependent increase in activation of
      the MAPK pathway. RAD001 treatment also led to MAPK activation in a mouse model
      of prostate cancer. We further show that rapamycin-induced MAPK activation occurs
      in both normal cells and cancer cells lines and that this feedback loop depends
      on an S6K-PI3K-Ras pathway. Significantly, pharmacological inhibition of the MAPK
      pathway enhanced the antitumoral effect of mTORC1 inhibition by rapamycin in
      cancer cells in vitro and in a xenograft mouse model. Taken together, our
      findings identify MAPK activation as a consequence of mTORC1 inhibition and
      underscore the potential of a combined therapeutic approach with mTORC1 and MAPK
      inhibitors, currently employed as single agents in the clinic, for the treatment
      of human cancers.

PMID- 18725989
TI  - Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate
      cancer in a preclinical mouse model.
AB  - The AKT/mammalian target of rapamycin (AKT/mTOR) and ERK MAPK signaling pathways
      have been shown to cooperate in prostate cancer progression and the transition to
      androgen-independent disease. We have now tested the effects of combinatorial
      inhibition of these pathways on prostate tumorigenicity by performing preclinical
      studies using a genetically engineered mouse model of prostate cancer. We report
      here that combination therapy using rapamycin, an inhibitor of mTOR, and
      PD0325901, an inhibitor of MAPK kinase 1 (MEK; the kinase directly upstream of
      ERK), inhibited cell growth in cultured prostate cancer cell lines and tumor
      growth particularly for androgen-independent prostate tumors in the mouse model.
      We further showed that such inhibition leads to inhibition of proliferation and
      upregulated expression of the apoptotic regulator Bcl-2-interacting mediator of
      cell death (Bim). Furthermore, analyses of human prostate cancer tissue
      microarrays demonstrated that AKT/mTOR and ERK MAPK signaling pathways are often
      coordinately deregulated during prostate cancer progression in humans. We
      therefore propose that combination therapy targeting AKT/mTOR and ERK MAPK
      signaling pathways may be an effective treatment for patients with advanced
      prostate cancer, in particular those with hormone-refractory disease.

PMID- 18725990
TI  - Misfolded proteins activate factor XII in humans, leading to kallikrein formation
      without initiating coagulation.
AB  - When blood is exposed to negatively charged surface materials such as glass, an
      enzymatic cascade known as the contact system becomes activated. This cascade is
      initiated by autoactivation of Factor XII and leads to both coagulation (via
      Factor XI) and an inflammatory response (via the kallikrein-kinin system).
      However, while Factor XII is important for coagulation in vitro, it is not
      important for physiological hemostasis, so the physiological role of the contact
      system remains elusive. Using patient blood samples and isolated proteins, we
      identified a novel class of Factor XII activators. Factor XII was activated by
      misfolded protein aggregates that formed by denaturation or by surface
      adsorption, which specifically led to the activation of the kallikrein-kinin
      system without inducing coagulation. Consistent with this, we found that Factor
      XII, but not Factor XI, was activated and kallikrein was formed in blood from
      patients with systemic amyloidosis, a disease marked by the accumulation and
      deposition of misfolded plasma proteins. These results show that the kallikrein
      kinin system can be activated by Factor XII, in a process separate from the
      coagulation cascade, and point to a protective role for Factor XII following
      activation by misfolded protein aggregates.

PMID- 18725991
TI  - The elusive physiologic role of Factor XII.
AB  - Physiologic hemostasis upon injury involves many plasma proteins in a well
      regulated cascade of proteolytic reactions to form a clot. Deficiency of blood
      coagulation Factors VIII, IX, or XI is associated with hemophilia. Factor XII
      (FXII) autoactivates by contact with a variety of artificial or biologic
      negatively charged surfaces (contact activation), resulting in blood coagulation
      and activation of the inflammatory kallikrein-kinin and complement systems.
      However, surprisingly, individuals deficient in FXII rarely suffer from bleeding
      disorders. Most biologic surfaces that activate FXII become expressed in disease
      states. Investigators have long searched for physiologic activators of FXII and
      its role in vivo. In this issue of the JCI, Maas et al. show that misfolded
      protein aggregates produced during systemic amyloidosis allow for plasma FXIIa
      and prekallikrein activation and increased formation of kallikrein-C1 inhibitor
      complexes, without Factor XIa activation and coagulation (see the related article
      beginning on page 3208). This study describes a novel biologic surface for FXII
      activation and activity, which initiates inflammatory events independent of
      hemostasis.

PMID- 18725992
TI  - Platelet adhesion: a game of catch and release.
AB  - The interaction of circulating platelets with the vessel wall involves a process
      of cell catch and release, regulating cell rolling, skipping, or firm adhesion
      and leading to thrombus formation in flowing blood. In this regard, the
      interaction of platelet glycoprotein Ibalpha (GPIbalpha) with its adhesive
      ligand, vWF, is activated by shear force and critical for platelet adhesion to
      the vessel wall. In this issue of the JCI, Yago and colleagues show how gain-of
      function mutations in the GPIbalpha-binding vWF A1 domain disrupt intramolecular
      interactions within WT vWF A1 that regulate binding to GPIbalpha and flow
      enhanced platelet rolling and adhesion (see the related article beginning on page
      3195). Together, these studies reveal molecular mechanisms regulating GPIbalpha
      vWF bond formation and platelet adhesion under shear stress.

PMID- 18725993
TI  - Cotargeting survival signaling pathways in cancer.
AB  - Mammalian target of rapamycin (mTOR) is a component of a signaling pathway
      (PTEN/PI3K/AKT) that is frequently dysregulated in cancer. However, its precise
      relationship to the MAPK cascade (Ras/Raf/MEK/ERK), another pathway often
      implicated in tumorigenesis, has not been well defined. Recent evidence from
      tissue specimens obtained from patients who have received mTOR inhibitors
      suggests that ERK may be activated in response to mTOR interruption. In this
      issue of the JCI, Waugh Kinkade et al. and Carracedo et al. examine the
      relationship between these pathways in prostate and breast cancer cell model
      systems (see the related articles beginning on pages 3051 and 3065,
      respectively). Their findings suggest a link between inhibition of mTOR and ERK
      activation, possibly reflecting interruption of a novel negative S6K1-dependent
      feedback loop. Significantly, both groups observed that simultaneous inhibition
      of MEK/ERK and mTOR resulted in substantially enhanced antitumor effects both in
      vitro and in vivo. Together, these findings suggest that concurrent interruption
      of complementary signaling pathways warrants further investigation in cancer
      therapy.

PMID- 18725994
TI  - Inhibition of angiogenic factor production from murine mast cells by an
      antiallergic agent (epinastine hydrochloride) in vitro.
AB  - Angiogenesis is an important event both in the development of allergic
      inflammatory responses and in the pathophysiology of tissue remodeling in
      allergic diseases. In the present study, therefore, we examined the influence of
      antihistamines on angiogenesis through the choice of epinastine hydrochloride
      (EP) and murine mast cells in vitro. Mast cells (5 x 10(5) cells/mL)
      presensitized with murine IgE specific for ovalbumin (OVA) were stimulated with
      10 ng/mL OVA in the presence of various concentrations of EP for 4 hours. The
      levels of angiogenesis factors, keratinocyte-derived chemokine (KC), tumor
      necrosis factor-alpha (TNF), and vascular endothelial growth factor (VEGF) in
      culture supernatants, were examined by ELISA. We also examined mRNA expression
      for the angiogenesis factors by RT-PCR. EP significantly inhibited the production
      of KC, TNF, and VEGF induced by IgE-dependent mechanism at more than 25 ng/mL.
      Semiquantitative analysis using RT-PCR showed that EP also significantly reduced
      mRNA expressions for KC, TNF, and VEGF. These results strongly suggest that EP
      suppresses angiogenesis factor production through the inhibition of mRNA
      expression in mast cells and results in favorable modification of clinical
      conditions of allergic diseases.

PMID- 18725995
TI  - Detection of large numbers of novel sequences in the metatranscriptomes of
      complex marine microbial communities.
AB  - BACKGROUND: Sequencing the expressed genetic information of an ecosystem
      (metatranscriptome) can provide information about the response of organisms to
      varying environmental conditions. Until recently, metatranscriptomics has been
      limited to microarray technology and random cloning methodologies. The
      application of high-throughput sequencing technology is now enabling access to
      both known and previously unknown transcripts in natural communities.
      METHODOLOGY/PRINCIPAL FINDINGS: We present a study of a complex marine
      metatranscriptome obtained from random whole-community mRNA using the GS-FLX
      Pyrosequencing technology. Eight samples, four DNA and four mRNA, were processed
      from two time points in a controlled coastal ocean mesocosm study (Bergen,
      Norway) involving an induced phytoplankton bloom producing a total of 323,161,989
      base pairs. Our study confirms the finding of the first published
      metatranscriptomic studies of marine and soil environments that
      metatranscriptomics targets highly expressed sequences which are frequently
      novel. Our alternative methodology increases the range of experimental options
      available for conducting such studies and is characterized by an exceptional
      enrichment of mRNA (99.92%) versus ribosomal RNA. Analysis of corresponding
      metagenomes confirms much higher levels of assembly in the metatranscriptomic
      samples and a far higher yield of large gene families with >100 members,
      approximately 91% of which were novel. CONCLUSIONS/SIGNIFICANCE: This study
      provides further evidence that metatranscriptomic studies of natural microbial
      communities are not only feasible, but when paired with metagenomic data sets,
      offer an unprecedented opportunity to explore both structure and function of
      microbial communities--if we can overcome the challenges of elucidating the
      functions of so many never-seen-before gene families.

PMID- 18725996
TI  - Multimodal Pressure Flow Analysis: Application of Hilbert Huang Transform in
      Cerebral Blood Flow Regulation.
AB  - Quantification of nonlinear interactions between two nonstationary signals
      presents a computational challenge in different research fields, especially for
      assessments of physiological systems. Traditional approaches that are based on
      theories of stationary signals cannot resolve nonstationarity-related issues and,
      thus, cannot reliably assess nonlinear interactions in physiological systems. In
      this review we discuss a new technique "Multi-Modal Pressure Flow method (MMPF)"
      that utilizes Hilbert-Huang transformation to quantify dynamic cerebral
      autoregulation (CA) by studying interaction between nonstationary cerebral blood
      flow velocity (BFV) and blood pressure (BP). CA is an important mechanism
      responsible for controlling cerebral blood flow in responses to fluctuations in
      systemic BP within a few heart-beats. The influence of CA is traditionally
      assessed from the relationship between the well-pronounced systemic BP and BFV
      oscillations induced by clinical tests. Reliable noninvasive assessment of
      dynamic CA, however, remains a challenge in clinical and diagnostic medicine.In
      this brief review we: 1) present an overview of transfer function analysis (TFA)
      that is traditionally used to quantify CA; 2) describe the a MMPF method and its
      modifications; 3) introduce a newly developed automatic algorithm and engineering
      aspects of the improved MMPF method; and 4) review clinical applications of MMPF
      and its sensitivity for detection of CA abnormalities in clinical studies. The
      MMPF analysis decomposes complex nonstationary BP and BFV signals into multiple
      empirical modes adaptively so that the fluctuations caused by a specific
      physiologic process can be represented in a corresponding empirical mode. Using
      this technique, we recently showed that dynamic CA can be characterized by
      specific phase delays between the decomposed BP and BFV oscillations, and that
      the phase shifts are significantly reduced in hypertensive, diabetics and stroke
      subjects with impaired CA. In addition, the new technique enables reliable
      assessment of CA using both data collected during clinical test and spontaneous
      BP/BFV fluctuations during baseline resting conditions.

PMID- 18725997
TI  - Kriging and Semivariogram Deconvolution in the Presence of Irregular Geographical
      Units.
AB  - This paper presents a methodology to conduct geostatistical variography and
      interpolation on areal data measured over geographical units (or blocks) with
      different sizes and shapes, while accounting for heterogeneous weight or kernel
      functions within those units. The deconvolution method is iterative and seeks the
      pointsupport model that minimizes the difference between the theoretically
      regularized semivariogram model and the model fitted to areal data. This model is
      then used in area-to-point (ATP) kriging to map the spatial distribution of the
      attribute of interest within each geographical unit. The coherence constraint
      ensures that the weighted average of kriged estimates equals the areal datum.This
      approach is illustrated using health data (cancer rates aggregated at the county
      level) and population density surface as a kernel function. Simulations are
      conducted over two regions with contrasting county geographies: the state of
      Indiana and four states in the Western United States. In both regions, the
      deconvolution approach yields a point support semivariogram model that is
      reasonably close to the semivariogram of simulated point values. The use of this
      model in ATP kriging yields a more accurate prediction than a naive point kriging
      of areal data that simply collapses each county into its geographic centroid. ATP
      kriging reduces the smoothing effect and is robust with respect to small
      differences in the point support semivariogram model. Important features of the
      point-support semivariogram, such as the nugget effect, can never be fully
      validated from areal data. The user may want to narrow down the set of solutions
      based on his knowledge of the phenomenon (e.g., set the nugget effect to zero).
      The approach presented avoids the visual bias associated with the interpretation
      of choropleth maps and should facilitate the analysis of relationships between
      variables measured over different spatial supports.

PMID- 18725998
TI  - Borane B-C Bond Cleavage by a Low-Coordinate Iron Hydride Complex and N-N Bond
      Cleavage by the Hydridoborate Product.
AB  - The iron(II) hydride dimers [L(R)Fe(MU-H)(2)FeL(R)] (L(Me) = 2,4-bis(2,6
      diisopropylphenylimino) pent-3-yl; L(tBu) = 2,2,6,6-tetramethyl-3,5-bis(2,6
      diisopropylphenylimino)hept-4-yl) abstract hydrocarbyl groups from BR'(3) (R' =
      Et, Ph) to give L(R)FeR' and L(R)Fe(MU-H)(2)BR'(2). Mechanistic studies with R =
      R' = Me are consistent with a process in which the hyride dimer opens one Fe-H
      bond, and subsequent B-H bond formation is concerted with dissociation of an Fe-H
      unit. Cleavage of boron-carbon bonds is likely to proceed at least in part from
      transient quaternary borate anions. In a separate bond-breaking reaction,
      L(Me)Fe(MU-H)(2)BEt(2) reacts with N(2)H(4) to eject H(2) from the bridging
      hydrides and cleave the N-N bond in the diaminoborate complex L(Me)Fe(MU
      NH(2))(2)BEt(2). These novel bond-breaking reactions are facilitated by the low
      coordination number at the iron(II) center.

PMID- 18726000
TI  - In reply to Zou et al. "New amyloid plaques or a game of hide-and-seek?".

PMID- 18725999
TI  - Platelet glycoprotein Ibalpha forms catch bonds with human WT vWF but not with
      type 2B von Willebrand disease vWF.
AB  - Arterial blood flow enhances glycoprotein Ibalpha (GPIbalpha) binding to vWF,
      which initiates platelet adhesion to injured vessels. Mutations in the vWF A1
      domain that cause type 2B von Willebrand disease (vWD) reduce the flow
      requirement for adhesion. Here we show that increasing force on GPIbalpha/vWF
      bonds first prolonged ("catch") and then shortened ("slip") bond lifetimes. Two
      type 2B vWD A1 domain mutants, R1306Q and R1450E, converted catch bonds to slip
      bonds by prolonging bond lifetimes at low forces. Steered molecular dynamics
      simulations of GPIbalpha dissociating from the A1 domain suggested mechanisms for
      catch bonds and their conversion by the A1 domain mutations. Catch bonds caused
      platelets and GPIbalpha-coated microspheres to roll more slowly on WT vWF and WT
      A1 domains as flow increased from suboptimal levels, explaining flow-enhanced
      rolling. Longer bond lifetimes at low forces eliminated the flow requirement for
      rolling on R1306Q and R1450E mutant A1 domains. Flowing platelets agglutinated
      with microspheres bearing R1306Q or R1450E mutant A1 domains, but not WT A1
      domains. Therefore, catch bonds may prevent vWF multimers from agglutinating
      platelets. A disintegrin and metalloproteinase with a thrombospondin type 1 motif
      13 (ADAMTS-13) reduced platelet agglutination with microspheres bearing a
      tridomain A1A2A3 vWF fragment with the R1450E mutation in a shear-dependent
      manner. We conclude that in type 2B vWD, prolonged lifetimes of vWF bonds with
      GPIbalpha on circulating platelets may allow ADAMTS-13 to deplete large vWF
      multimers, causing bleeding.

PMID- 18726001
TI  - Regulation of the Arabidopsis GSK3-like kinase BRASSINOSTEROID-INSENSITIVE 2
      through proteasome-mediated protein degradation.
AB  - Glycogen synthase kinase 3 (GSK3) is a unique serine/threonine kinase that is
      implicated in a variety of cellular processes and is regulated by phosphorylation
      or protein-protein interaction in animal cells. BIN2 is an Arabidopsis GSK3-like
      kinase that negatively regulates brassinosteroid (BR) signaling. Genetic studies
      suggested that BIN2 is inhibited in response to BR perception at the cell surface
      to relieve its inhibitory effects on downstream targets; however, little is known
      about biochemical mechanisms of its inhibition. Here, we show that BIN2 is
      regulated by proteasome-mediated protein degradation. Exogenous application of a
      BR biosynthesis inhibitor and an active BR increased and decreased the amount of
      BIN2 proteins, respectively. Interestingly, the gain-of-function bin2-1 mutation
      significantly stabilizes BIN2, making it unresponsive to BR-induced BIN2
      depletion. Exogenous application of different plant growth hormones revealed that
      BIN2 depletion is specifically induced by BR through a functional BR receptor,
      while treatment of a proteasome inhibitor, MG132, not only prevented the BR
      induced BIN2 depletion but also nullified the inhibitory effect of BR on the BIN2
      kinase activity. Taken together, our results strongly suggest that proteasome
      mediated protein degradation constitutes an important regulatory mechanism for
      restricting the BIN2 activity.

PMID- 18726002
TI  - Cuticular lipid mass and desiccation rates in Glossina pallidipes:
      interpopulation variation.
AB  - Tsetse flies, Glossina pallidipes (Diptera: Glossinidae) are said to have strong
      dispersal tendencies. Gene flow among these populations is estimated to be the
      theoretical equivalent of no more than one or two reproducing flies per
      generation, thereby raising the hypothesis of local regimes of natural selection.
      Flies were sampled from four environmentally diverse locations in Kenya to
      determine whether populations are homogeneous in desiccation tolerance and
      cuticular lipids. Cuticular hydrocarbon fractions known to act as sex pheromones
      do not differ among populations, thereby eliminating sexual selection as an
      isolating mechanism. Cuticular lipid quantities vary among populations and are
      not correlated with prevailing temperatures, humidities, and normalized density
      vegetation indices. Females demonstrate a stronger correlation than males between
      cuticular lipid mass and body weight. Desiccation rates also vary among
      populations, but are not correlated with the amounts of cuticular lipid. Chemical
      analysis of cuticular hydrocarbons by gas chromatography-mass spectroscopy shows
      that one of the four populations has more 11,15- and 11,21-dimethyl-31
      hydrocarbon on females. These results are discussed in the context of population
      differences and estimates of gene flow.

PMID- 18726003
TI  - Preconditioning of carbon monoxide releasing molecule-derived CO attenuates LPS
      induced activation of HUVEC.
AB  - OBJECTIVE: To investigate the effects and potential mechanisms of preconditioning
      of tricarbonyldichlororuthenium (III) dimer (CORM-2)-liberated CO on LPS-induced
      activation of endothelial cells (HUVEC). METHODS: HUVEC were pretreated with CORM
      2 at the concentration of 50 or 100 microM for 2 hrs, washed and stimulated with
      LPS (10 microg/ml) for additional 4 hrs. Activation (oxidative stress) of HUVEC
      was assessed by measuring intracellular oxidation of DHR 123 or nitration of DAF
      FM, specific H(2)O(2) and NO fluorochromes, respectively. The expression of HO-1,
      iNOS (Western blot) and ICAM-1 (cell ELISA) proteins and activation of
      inflammation-relevant transcription factor, NF-kappaB (EMSA) were assessed. In
      addition, PMN adhesion to HUVEC was also assessed. RESULTS: The obtained data
      indicate that pretreatment of HUVEC with CORM-2 results in: 1) decrease of LPS
      induced production of ROS and NO; 2) up-regulation of HO-1 but decrease in iNOS
      at the protein levels; 3) inhibition of LPS-induced activation of NF-kappaB; and
      4) downregulation of expression of ICAM-1, and this was accompanied by a decrease
      of PMN adhesion to LPS-stimulated HUVEC. CONCLUSIONS: Preconditioning of CO
      liberated by CORM-2 elicited its anti-inflammatory effects by interfering with
      the induction of intracellular oxidative stress. In addition, it also supports
      the notion that CO is a potent inhibitor of iNOS and NF-kappaB.

PMID- 18726004
TI  - Aberrant c-erbB2 expression in cell clusters overlying focally disrupted breast
      myoepithelial cell layers: a trigger or sign for emergence of more aggressive
      cell clones?
AB  - Our recent studies revealed that cell clusters overlying focal myoepithelial cell
      layer disruption (FMCLD) had a significantly higher frequency of genetic
      instabilities and expression of invasion-related genes than their adjacent
      counterparts within the same duct. Our current study attempted to assess whether
      these cell clusters would also have elevated c-erbB2 expression. Human breast
      tumors (n=50) with a high frequency of FMCLD were analyzed with double
      immunohistochemistry, real-time RT-PCR, and chromogenic in situ hybridization for
      c-erbB2 protein and gene expression. Of 448 FMCLD detected, 404 (90.2%) were
      associated with cell clusters that had intense c-erbB2 immunoreactivities
      primarily in their cytoplasm, in contrast to their adjacent counterparts within
      the same duct, which had no or barely detectable c-erbB2 expression. These c
      erbB2 positive cells were arranged as tongue-like projections, "puncturing" into
      the stroma, and about 20% of them were in direct continuity with tube-like
      structures that resembled blood vessels. Aberrant c-erbB2 expression was also
      seen in clusters of architecturally normal-appearing ducts that had distinct
      cytological abnormalities in both ME and epithelial cells, whereas not in their
      clear-cut normal counterparts. Molecular assays detected markedly higher c-erbB2
      mRNA and gene amplification in cell clusters associated with FMCLD than in those
      associated with non-disrupted ME cell layers. Our findings suggest that cell
      clusters overlying FMCLD may represent the precursors of pending invasive
      lesions, and that aberrant c-erbB2 expression may trigger or signify the
      emergence of biologically more aggressive cell clones.

PMID- 18726005
TI  - Highly Cooperative Tetrametallic Ruthenium-mu-Oxo-mu-Hydroxo Catalyst for the
      Alcohol Oxidation Reaction.
AB  - The tetrametallic ruthenium-oxo-hydroxo-hydride complex
      {[(PCy(3))(CO)RuH](4)(mu(4)-O)(mu(3)-OH)(mu(2)-OH)} (1) was synthesized in two
      steps from the monomeric complex (PCy(3))(CO)RuHCl (2). The tetrameric complex 1
      was found to be a highly effective catalyst for the transfer dehydrogenation of
      alcohols. Complex 1 showed a different catalytic activity pattern towards primary
      and secondary benzyl alcohols, as indicated by the Hammett correlation for the
      oxidation reaction of p-X-C(6)H(4)CH(2)OH (rho = -0.45) and p-X
      C(6)H(4)CH(OH)CH(3) (rho = +0.22) (X = OMe, CH(3), H, Cl, CF(3)). Both a
      sigmoidal curve from the plot of initial rate vs [PhCH(OH)CH(3)] (K(0.5) = 0.34
      M; Hill coefficient, n = 4.2+/-0.1) and the phosphine inhibition kinetics
      revealed the highly cooperative nature of the complex for the oxidation of
      secondary alcohols.

PMID- 18726006
TI  - Talking across time: Using reported speech as a communicative resource in
      amnesia.
AB  - BACKGROUND: Patients with amnesia may have more than pure memory deficits, as
      evidenced by reports of subtle linguistic impairments on formal laboratory tasks
      in the amnesic patient HM. However, little attention has been given to the impact
      of memory impairments on language use in regular, colloquial interactions. We
      analysed reported speech use by individuals with amnesia. Reported speech (RS),
      in which speakers represent thoughts/words from another time and/or place,
      requires management of two temporal frames, making it an interesting discourse
      practice in which to explore the impact of memory deficits on interactional
      aspects of communication. AIMS: This study: (1) documents frequency, type, and
      temporal contexts of reported speech used in discourse samples; (2) compares
      reported speech use by amnesic and comparison participants; (3) examines the
      interactional character of reported speech use in these discourse samples.
      METHODS AND PROCEDURES: Derived from a broader study of the discourse practices
      of individuals with amnesia, this study uses quantitative group comparisons and
      close discourse analysis to analyse reported speech episodes (RSEs) in
      interactional discourse samples between a clinician and each of 18 participants,
      9 individuals with amnesia and 9 comparison participants (NC). OUTCOMES AND
      RESULTS: Reported speech was used by all participants. However, significantly
      fewer RSEs were produced in amnesia sessions (273) than in NC sessions (554). No
      significant group differences were observed for type or temporal domain. In
      addition, for the participants with amnesia, post-amnesia past RSEs differed
      qualitatively from the other RSEs in the data. CONCLUSIONS: These findings have
      important implications for understanding the interdependent relationship of
      memory and language, point to the value of examining interactional aspects of
      communication in the empirical study of brain-behaviour relationships, and
      reconceptualise interaction as a target in the remediation of functional
      communication following brain injury.

PMID- 18726007
TI  - An Analysis of Alternatives to New York City's Current Marijuana Arrest and
      Detention Policy.
AB  - During the 1990s, the New York Police Department (NYPD) instituted a policy of
      arresting and detaining people for minor offenses that occur in public as part of
      their quality-of-life (hereafter QOL) policing initiative. The number of NYPD
      arrests for smoking marijuana in public view (MPV) increased from 3,000 in 1994
      to over 50,000 in 2000, and have been about 30,000 in the mid 2000s. Most of
      these arrestees (84%) have been minority; blacks have been 2.7 more likely and
      Hispanics 1.8 times more likely to be detained than whites for an MPV arrest.
      Minorities have been most likely to receive more severe dispositions, even
      controlling for demographics and prior arrest histories.This paper examines the
      pros and cons of the current policy; this is compared with possible alternatives
      including the following: arrest and issue a desk appearance ticket (DAT); issue a
      non-criminal citation (violation); street warnings; and tolerate public marijuana
      smoking. The authors recommend that the NYPD change to issuing DATs on a routine
      basis. Drug policy reformers might wish to further pursue changing statutes
      regarding smoking marijuana in public view into a violation (noncriminal) or
      encourage the wider use of street warnings. Any of these policy changes would
      help reduce the disproportionate burden on minorities associated with the current
      arrest and detention policy. These policies could help maintain civic norms
      against smoking marijuana in public.

PMID- 18726009
TI  - Photodynamic effect of lanthanide derivatives of meso-tetra(N-methyl-4
      pyridyl)porphine against Staphylococcus aureus.
AB  - Photodynamic therapy (PDT), used for cancer treatment, is also an alternative
      method for eradication of drug-resistant bacteria. This method utilizes a
      nontoxic light-activated dye, called a photosensitizer, and visible light to
      produce reactive oxygen species that lead to bacterial cell death. The purpose of
      this study was to investigate the bactericidal effect of PDT using lanthanide
      derivatives of meso-tetra(N-methyl-4-pyridyl)porphine against Staphylococcus
      aureus strains. The new photosensitizers appeared to be photodynamically
      ineffective. No enhancement of antistaphylococcal activity of TMPyP was observed
      after the conjugation of the porphyrin with lanthanide ions. Additionally, a
      significant difference in the susceptibility of two bacterial strains to
      unmodified TMPyP was observed.

PMID- 18726008
TI  - The essential function of Swc4p - a protein shared by two chromatin-modifying
      complexes of the yeast Saccharomyces cerevisiae - resides within its N-terminal
      part.
AB  - The Swc4p protein, encoded by an essential gene, is shared by two chromatin
      remodeling complexes in Saccharomyces cerevisiae cells: NuA4 (nucleosome
      acetyltransferase of H4) and SWR1. The SWR1 complex catalyzes ATP-dependent
      exchange of the nucleosomal histone H2A for H2AZ (Htz1p). The activity of NuA4 is
      responsible mainly for the acetylation of the H4 histone but also for the
      acetylation of H2A and H2AZ. In this work we investigated the role of the Swc4p
      protein. Using random mutagenesis we isolated a collection of swc4 mutants and
      showed that the essential function of Swc4p resides in its N-terminal part,
      within the first 269 amino acids of the 476-amino acid-long protein. We also
      demonstrated that Swc4p is able to accommodate numerous mutations without losing
      its functionality under standard growth conditions. However, when swc4 mutants
      were exposed to methyl methanesulfonate (MMS), hydroxyurea or benomyl, severe
      growth deficiencies appeared, pointing to an involvement of Swc4p in many
      chromatin-based processes. The mutants' phenotypes did not result from an
      impairment of histone acetylation, as in the mutant which bears the shortest
      isolated variant of truncated Swc4p, the level of overall H4 acetylation was
      unchanged.

PMID- 18726010
TI  - Oligoarenes as molecular backbones of catalysts: synthesis and applications.
AB  - This feature article highlights our recent work on oligoarene-type catalysts. We
      developed a synthetic method for multifunctionalized oligoarenes using a
      repetitive two-step strategy. The method was then applied to the preparation of
      oligoarene-type phosphines, which were used for palladium-catalyzed cross
      coupling of halobenzenes with Grignard reagents.

PMID- 18726011
TI  - Synthetic applications of carbolithiation transformations.
AB  - Carbolithiation reactions are exceptionally versatile transformations which have
      been utilised in a remarkably diverse and creative manner. In this review we
      outline the background and scope of these reactions and then focus on their use
      in organic synthesis with a particular emphasis on literature examples published
      since 2000.

PMID- 18726012
TI  - Alkylpyrrolidiniumtrialkoxysilyl iodides as organic iodide sources for dye
      sensitised solar cells.
AB  - Two new alkylpyrrolidiniumtriethoxysilyl iodides have been developed as iodide
      sources for DSSCs; the compound with an undecyl spacer between the siloxane and
      the pyrrolidinium moieties furnished higher open circuit voltages than the propyl
      analogue and higher efficiencies at low light intensity.

PMID- 18726013
TI  - Anti-Markovnikov hydroarylation of styrenes catalyzed by an in situ generated
      ruthenium complex.
AB  - An efficient and practical catalytic system for the anti-Markovnikov ruthenium
      catalyzed hydroarylation of styrenes with acetophenone, allowing a
      straightforward access to bibenzyl backbones, is described for the first time:
      this process, involving regioselective C-H bond activation, is complementary to a
      Friedel-Crafts type reaction giving the branched adduct.

PMID- 18726014
TI  - Transcription monitoring using fused RNA with a dye-binding light-up aptamer as a
      tag: a blue fluorescent RNA.
AB  - The "light-up" RNA aptamer-Hoechst pair can be used as a fluorescent tag to
      monitor transcription processes.

PMID- 18726015
TI  - X-Shaped polyphilics: liquid crystal honeycombs with single-molecule walls.
AB  - X-Shaped ternary five-block molecules, composed of a rigid p-terphenyl core, two
      terminal glycerol groups and two flexible n-alkyl or semiperfluorinated chains
      fixed laterally to opposite sides of the terphenyl moiety, form liquid
      crystalline phases built up of honeycomb-like arrays of polygonal cylinders,
      where the rod-like aromatic cores form cylinder walls with a thickness equal to
      the width of a single molecule.

PMID- 18726016
TI  - Highly efficient construction of large molecular cavity using 1,3-alternate
      tetraoxacalix[2]arene[2]triazine as a platform.
AB  - In the presence of K(2)CO(3) in refluxing THF, dichloro-substituted
      tetraoxacalix[2]arene[2]triazine, a readily available macrocyclic compound from
      cyanuric acid chloride and benzyl 1,3-dihydroxybenzoate, underwent highly
      efficient nucleophilic displacement reactions with bis-nucleophilic reagents of
      different geometry, length and chirality in a 2+2 fashion to produce large and
      size-tunable cavity bis-tetraoxacalix[2]arene[2]triazines in good to excellent
      yields.

PMID- 18726017
TI  - Chloroalkylsulfonate ionic liquids by ring opening of sultones with organic
      chloride salts.
AB  - An efficient route to prepare ionic liquids with chloroalkylsulfonate anions is
      presented; the synthesis proceeds in a one-step ring-opening reaction of sultones
      with an organic chloride salt and provides a very attractive access to new anion
      functionalised ionic liquids.

PMID- 18726018
TI  - Protein modulation of electrochemical signals: application to immunobiosensing.
AB  - Herein we present a label-free immunobiosensor based on the modulation of
      amperometric signals of surface bound redox species when immersed in a protein
      environment which is applicable to either the detection of antibodies or the
      detection of small molecules such as drugs or pesticides.

PMID- 18726019
TI  - Monomeric, dimeric and hexameric resorcin[4]arene assemblies with alcohols in
      apolar solvents.
AB  - Resorcin[4]arenes in an apolar solvent containing alcohols exist in three forms
      of self-assembled aggregates which have been characterised by the technique of
      diffusion NMR spectroscopy.

PMID- 18726020
TI  - Facile and highly efficient synthesis of fluorinated heterocycles via Prins
      cyclization in ionic liquid hydrogen fluoride salts.
AB  - Prins cyclization of homoallylic alcohols, thiols, and amines with various
      aldehydes in an ionic liquid HF salt (Et(4)NF.5HF) afforded the corresponding 4
      fluorinated heterocycles in excellent yields.

PMID- 18726022
TI  - Triethylsilane as a mild and efficient reducing agent for the preparation of
      alkanethiol-capped gold nanoparticles.
AB  - The reaction of HAuCl(4).4H(2)O and n-C(12)H(25)SH with 1 equiv. of Et(3)SiH in
      an organic solvent affords spherical gold nanoparticles (AuNPs) with narrow
      dispersity.

PMID- 18726021
TI  - The first example of enamine-Lewis acid cooperative bifunctional catalysis:
      application to the asymmetric aldol reaction.
AB  - (-)-Sparteine directed lithiation of N-Boc-pyrrolidine, alkylation with
      chloromethylboronate pinacol ester and acid-based deprotection provides
      homoboroproline HX salt in 94% ee, which is then an efficient enamine-type
      pyrrolidine catalyst in an asymmetric aldol reaction when neutralised and
      especially when esterified in situ with a tartrate ester, for example, providing
      90% ee of the aldol adduct derived from acetone and p-nitrobenzaldehyde.

PMID- 18726023
TI  - Direct generation of hydrogen peroxide from formic acid and O2 using
      heterogeneous Pd/gamma-Al2O3 catalysts.
AB  - Hydrogen peroxide formation is achieved with remarkable productivity at ambient
      conditions (25 degrees C and atmospheric pressure) in aqueous medium using a
      heterogeneous catalytic system; formic acid is decomposed in the presence of a
      continuous flow of O(2) over Pd/gamma-Al(2)O(3) catalyst leading to the
      generation of hydrogen peroxide; the addition of a negligible amount of bromide
      ion improves the selectivity of the reaction.

PMID- 18726024
TI  - Biaryl phosphite-oxazolines from hydroxyl aminoacid derivatives: highly efficient
      modular ligands for Ir-catalyzed hydrogenation of alkenes.
AB  - High enantioselectivities and activities are achieved in the Ir-catalyzed
      hydrogenation of several unfunctionalized olefins using modular biaryl phosphite
      oxazoline ligands from hydroxyl aminoacid derivatives; the presence of a biaryl
      phosphite group is crucial to this success.

PMID- 18726025
TI  - Synthetic paramontroseite VO2 with good aqueous lithium-ion battery performance.
AB  - Synthetic paramontroseite VO(2) has been successfully obtained using a simple
      chemical reaction route for the first time after fifty years; the paramontroseite
      phase shows a conducting property and good aqueous lithium ion battery
      performance.

PMID- 18726026
TI  - Nanometre resolution using high-resolution scanning electron microscopy
      corroborated by atomic force microscopy.
AB  - The resolving power of high-resolution scanning electron microscopy was judged
      using topographical height data from atomic force microscopy in order to assess
      the technique as a tool for understanding nanoporous crystal growth.

PMID- 18726027
TI  - Giant molecular spoked wheels in giant voids: two-dimensional molecular self
      assembly goes big.
AB  - We present here the formation of giant pores in surface-confined molecular
      networks of a triangular-shaped dehydrobenzo-[12]annulene derivative: the
      diameter of the pores reaches over 7 nm and the giant pores are used as templates
      to accommodate a giant molecular spoked wheel, which allows us to observe
      rotational and adsorption-desorption dynamics of single guest molecules.

PMID- 18726028
TI  - Proline-functionalised calix[4]arene: an anion-triggered hydrogelator.
AB  - A water-soluble, chiral calix[4]arene has been found to form hydrogels when
      triggered by the presence of specific anions, with efficacy linked to the
      Hofmeister series; the gel properties are modified by the associated cations, and
      gelation can be reversibly switched off by increasing pH.

PMID- 18726029
TI  - Controlled self-assembly and templated metallization of fibrinogen nanofibrils.
AB  - Fibrinogen (Fg) nanofibrils were prepared by the ethanol-induced self-assembly of
      Fg molecules, which can be used as fibrous scaffolds to organize gold
      nanoparticles (NPs).

PMID- 18726030
TI  - A simple chemosensor for Hg2+ and Cu2+ that works as a molecular keypad lock.
AB  - A new chemosensor which can detect Hg(2+) in water and Hg(2+)/Cu(2+) in
      acetonitrile and its application as a molecular keypad lock using Cu(2+) and F(-)
      as ionic inputs are demonstrated.

PMID- 18726031
TI  - Manipulating the cavity of a porous material changes the photoreactivity of
      included guests.
AB  - Changing an ether to a ketone within the framework of a bis-urea macrocycle has
      little effect on the supramolecular assembly of this building block into porous
      crystals but introduces a triplet sensitizer into the framework that dramatically
      alters the photochemical reactions of included guests.

PMID- 18726032
TI  - Cruciform oligo(phenylenevinylene) with a bipyridine bridge: synthesis, its
      rhenium(I) complex and photovoltaic properties.
AB  - A cruciform-shaped oligo(phenylenevinylene) (OPV) with a phosphorescent
      rhenium(I) chromophore incorporated at the centre and grafted triphenylamines
      around the periphery was designed as a new organic photovoltaic material, in
      which the chelation of rhenium(I) to the cruciform successfully constructs a
      three-dimensional intramolecular charge transfer system and extends the exciton
      lifetime; as a result, the rhenium-OPV complex shows a power conversion
      efficiency almost two times that of the metal ion-free parent compound.

PMID- 18726033
TI  - Molecular recognition in bisurea thermoplastic elastomers studied with pyrene
      based fluorescent probes and atomic force microscopy.
AB  - Fluorescence spectroscopy and atomic force microscopy (AFM) measurements using
      bisurea-pyrene probes show that they are randomly dispersed in the hard blocks of
      thermoplastic elastomers with matching bisurea groups, whereas they phase
      separate from polymers with non-matching or no bisurea groups.

PMID- 18726034
TI  - Thermally stable and photoreactive polylactides by the terminal conjugation of
      bio-based caffeic acid.
AB  - Caffeic acid terminally conjugated with polylactide showed high thermal stability
      and photoreactivity, and may be useful as a functional polylactide in the
      environmental and medical fields.

PMID- 18726035
TI  - Reversible solid optical sensor based on acyclic-type receptor immobilized SBA-15
      for the highly selective detection and separation of Hg(II) ion in aqueous media.
AB  - An acyclic receptor immobilized mesoporous silica (ARMS) was prepared by sol-gel
      reaction and its optical sensing ability was studied upon the addition of heavy
      metal ions in aqueous solution.

PMID- 18726036
TI  - Invisible photochromism of diarylethene derivatives.
AB  - Diarylethene derivatives with oxidized thiophene rings shift their absorption
      band to a shorter wavelength in the UV region upon photocyclization; no color
      change was observed during the photochromic reaction, and the invisible
      photochromism is advantageous for devices used under room light.

PMID- 18726037
TI  - Synthesis, structures, and properties of nine-, twelve-, and eighteen-membered N
      benzyloxyethyl cyclic alpha-peptoids.
AB  - N-Benzyloxyethyl cyclic alpha-peptoids of various size were prepared and their
      conformational features were investigated by means of computational,
      spectroscopic, and X-ray crystallographic studies.

PMID- 18726038
TI  - Supermolecule density functional calculations on the water exchange of aquated
      Al(III) species in aqueous solution.
AB  - Supermolecule density functional calculations suggest the dissociative (D)
      mechanism for the water exchange of aquated Al(iii) species in aqueous solution
      and the calculated results agree well with experimental data.

PMID- 18726039
TI  - A photosensitive {Ru-NO}6 nitrosyl bearing dansyl chromophore: novel NO donor
      with a fluorometric on/off switch.
AB  - The synthesis, fluorescence properties and NO photolability of
      [(Me(2)bpb)Ru(NO)(Ds-im)]BF(4), a {Ru-NO}(6) nitrosyl-fluorophore conjugate, have
      been investigated and its potential as a trackable NO donor has been evaluated.

PMID- 18726040
TI  - Multiple weak supramolecular interactions stabilize a surprisingly twisted As2L3
      assembly.
AB  - A combined crystallographic, DFT and NMR spectroscopic study of a flexible
      As(2)(3) assembly reveals temperature dependent conformational behavior in
      solution and a highly asymmetric structure stabilized by As-pi and edge-to-face
      aromatic interactions.

PMID- 18726041
TI  - [Cognitive impairment in normal pressure hydrocephalus (NPH). A proposal for
      clinical evaluation protocol].
AB  - Normal pressure hydrocephalus (NPH) is characterized by gait disturbance, urinary
      incontinence and dementia, and is associated with variable ventricular
      enlargement. The most accepted treatment of NPH is the placement of a
      cerebrospinal fluid shunt. Owing to the characteristics of the patients and the
      invasive nature of the surgical treatment, it is fundamental to detect those
      patients who could obtain a greater benefit from the treatment.
      Neuropsychological assessment of these patients could significantly contribute to
      a better diagnosis of NPH, determining a cognitive deterioration profile for
      these patients, allowing the assessment of treatment efficacy and helping to
      detect other additional causes of dementia. The aim of this study is to describe
      the cognitive deterioration profile of NPH patients and to present the clinical,
      functional and neuropsychological assessment protocol used in our hospital.

PMID- 18726042
TI  - [Osseous orbitotomies using a coronal flap: a retrospective study of 87
      intraorbital lesions].
AB  - OBJECTIVE: To present our experience in 80 patients with intraorbital tumours and
      lesions who underwent 87 osseous orbitotomies with coronal incision during a 12
      year period. MATERIAL, METHODS AND RESULTS: Hemangioma was the most frequent
      histologic diagnosis, being the intraconical retrobulbar compartment the most
      common location. Bilateral presentation of lesions occurred in 7 patients.
      Lateral and supero-lateral orbitotomies were preferably applied (87.35%). In
      90.80% of cases some kind of osteosynthesis was employed, 51.75% with bio
      resorbable plates. Intraoperative exposure or dura mater breakage occurred in 10
      patients. 45 transitory and 21 permanent postoperative complications were seen,
      being the nervous ones (diplopia and ptosis) the most frequent. Most of these
      were spontaneously solved in a short time period. 15 patients required multi
      disciplinary collaboration with neurosurgery. CONCLUSIONS: Coronal incision
      allows any bone orbitotomy, with security, guarantee and good aesthetic and
      functional results. Lateral and supero-lateral orbitotomies provide an ideal
      extradural approach to the retrobulbar compartment. An approach to the apex,
      orbital channel and medial compartment to the optic nerve, usually requires a
      combined neurosurgical approach through anterior cranial fossa. Orbitotomy
      fixation with bio-resorbable ostheosynthesis is an alternative to titanium
      plates. They can even be a first choice in paediatric age. The morbidity of this
      surgical technique is low.

PMID- 18726043
TI  - [Radiation-induced cranial tumors: clinical series and literature review].
AB  - Radiation induced tumors are well-known but rare complications of radiotherapy.
      Meningiomas are the most common radiation-induced (RI) cranial tumors, followed
      by gliomas and sarcomas, while other tumors as haemangioblastomas remain
      extremely exceptional. We present 7 patients with RI brain tumors diagnosed and
      treated at our institution between 1990 and 2006. Retrospective review of their
      clinical charts is supplied. All patients were irradiated during childhood as a
      treatment for another disease, and fulfilled the criteria of RI neoplasia. Four
      patients developed meningiomas and three developed other tumors (one
      glioblastoma, one softtissue sarcoma and one hemangioblastoma). In all cases a
      complete surgical removal was achieved. Preoperative assessment based on MRI
      supplied the correct diagnosis in six patients. The most important risks factors
      described in the literature for developing RI tumors are the age at which
      radiotherapy was administered and the dose of radiation applied. Differential
      diagnosis of RI tumors includes any tumor appearing after radiotheraphy,
      especially recurrences of the primary disease, as RI neoplasias are a rare
      complication. Even in cases with complete surgical resection, prognosis of this
      clinical entity is basically related to the histology of the RI tumor.

PMID- 18726044
TI  - [Embolization of indirect carotid-cavernous sinus fistula through the ophthalmic
      vein].
AB  - Indirect or dural carotid cavernous fistulas are abnormal connections between the
      cavernous sinus and meningeal branches of the external and/or internal carotid
      arteries. Most of them are idiopathic and occurs spontaneously. Symptoms vary
      from a tiny episcleral injection to a severe visual loss. Conservative therapy is
      recomended in cases with few symptoms and no leptomeningeal drainage, as
      spontaneous resolution is not infrequent. Whenever symptoms worsen, treatment of
      the fistula should be prescribed. Nowadays, transvenous endovascular treatment
      consisting of packing the cavernous sinus is the first choice. In most cases,
      cavernous sinus can be approached through the inferior petrosal sinus. However,
      sometimes that is not possible, and an approach directly through the superior
      ophthalmic vein could be necessary. We report a case of a patient with a dural
      carotid cavernous fistula treated with embolization of the cavernous sinus
      through the ophthalmic vein.

PMID- 18726045
TI  - Giant cell glioblastoma: review of the literature and illustrated case.
AB  - Giant cell glioblastoma is an infrequent variety of glioblastoma (5% of the
      cases). It has deserved a separate category in the World Health Organization
      classification of grade IV tumors. The clinical, imaging, histological and
      immunohistochemical characteristics, and the genetic alterations are reviewed.
      Treatment and prognosis are discussed and updated. The case of a patient that
      survived 19 months and died of spinal leptomeningeal metastases is illustrated.

PMID- 18726046
TI  - [Forestier-Rotes-Querol's disease. Ossification of the anterior cervical
      longitudinal ligament as a cause of dysphagia].
AB  - Forestier's disease or diffuse idiophatic skeletal hyperostosis is a systemic
      reumathological abnormality of unknown etiology. It produces
      calcificationossification of the anterior longitudinal ligament. The low dorsal
      region is the most affected in the raquis. These patients are tipically
      asymptomatic or with few symptoms (minimal joint pain, spinal pain, stiffness).
      Dysphagia is the most common symptom when the disease affects the cervical spine;
      less frequent is dyspnea, both secondary to extrinsic compression of the
      esophagus and trachea. Neurological complaints are quite rare. In the 1970s
      Resnick described specific radiological criteria for the diagnosis of Forestier's
      disease that are still used today. It affects men more frequently than women
      (2:1); the peak occurrence is in patients in their 60s. We present two cases
      diagnosed by severe difficulty with deglution, a 84 years-old woman and a 54
      years-old man; we operated on them for surgical decompression of the esophagus
      with resection of osteophytes C3-C4 and C5-C6 respectively through a conventional
      anterolateral neck approach. Relief of difficulty in swallowing was immediately
      ensued.

PMID- 18726047
TI  - Anterior third ventricle meningiomas. Report of two cases.
AB  - Third ventricle meningiomas are rare, representing approximately 0.15% of all
      meningiomas. The majority of third ventricular meningiomas are located
      posteriorly in the pineal region. Less commonly, they arise in the anterior part
      of the third ventricle. We report the cases of two patients with large and giant
      meningiomas originating in the anterior part of the third ventricle.

PMID- 18726048
TI  - [Spontaneous resolution of an asymptomatic intracranial arachnoid cyst].
AB  - Arachnoid cysts are commonly considered to be benign, congenial,
      extraparenchymatous anomalies. Small cyst are common incidental findings in
      children and adults. The aetiology and natural history of arachnoid cysts are not
      fully understood. In most cases, the presence of the cysts is detected on CT
      scans or MRI performed for other reasons. In the literature, there have been few
      documented cases of arachnoid cysts with spontaneous regression. We reports the
      case of a silvian arachnoid cyst, which disappeared spontaneously during the 13
      year-follow-up period. We review the cases previously reported and the mechanisms
      underlying the resolution of the arachnoid cysts are discussed.

PMID- 18726049
TI  - A cystic amelanotic melanoma metastasis to the brain: case report.
AB  - As far as we know, cyst formation in intracranial melanoma is rare, and only 15
      cases of intracranial amelanotic melanoma have been reported until now. A
      yellowish mass was observed in the frontal lobe. The content of the cyst
      consisted of old hematoma, xanthochromic fluid and necrotic tissue, was evacuated
      and the cyst wall was totally resected. No abnormal pigmentation was noted in the
      cyst wall and surrounding brain tissue. The imaging features of metastatic
      melanomas are distinctive due to the presence of melanin and the propensity for
      hemorrhage. Both hemorrhage and melanin can produce T1-weighted hyperintensity
      and T2-weighted signal intensity loss.

PMID- 18726050
TI  - Biodiversity offsets: two New Zealand case studies and an assessment framework.
AB  - Biodiversity offsets are increasingly being used for securing biodiversity
      conservation outcomes as part of sustainable economic development to compensate
      for the residual unavoidable impacts of projects. Two recent New Zealand examples
      of biodiversity offsets are reviewed-while both are positive for biodiversity
      conservation, the process by which they were developed and approved was based
      more on the precautionary principal than on any formal framework. Based on this
      review and the broader offset literature, an environmental framework for
      developing and approving biodiversity offsets, comprising six principles, is
      outlined: (1) biodiversity offsets should only be used as part of an hierarchy of
      actions that first seeks to avoid impacts and then minimizes the impacts that do
      occur; (2) a guarantee is provided that the offset proposed will occur; (3)
      biodiversity offsets are inappropriate for certain ecosystem (or habitat) types
      because of their rarity or the presence of threatened species within them; (4)
      offsets most often involve the creation of new habitat, but can include
      protection of existing habitat where there is currently no protection; (5) a
      clear currency is required that allows transparent quantification of values to be
      lost and gained in order to ensure ecological equivalency between cleared and
      offset areas; (6) offsets must take into account both the uncertainty involved in
      obtaining the desired outcome for the offset area and the time-lag that is
      involved in reaching that point.

PMID- 18726051
TI  - Adaptation as a political process: adjusting to drought and conflict in Kenya's
      drylands.
AB  - In this article, we argue that people's adjustments to multiple shocks and
      changes, such as conflict and drought, are intrinsically political processes that
      have uneven outcomes. Strengthening local adaptive capacity is a critical
      component of adapting to climate change. Based on fieldwork in two areas in
      Kenya, we investigate how people seek to access livelihood adjustment options and
      promote particular adaptation interests through forming social relations and
      political alliances to influence collective decision-making. First, we find that,
      in the face of drought and conflict, relations are formed among individuals,
      politicians, customary institutions, and government administration aimed at
      retaining or strengthening power bases in addition to securing material means of
      survival. Second, national economic and political structures and processes affect
      local adaptive capacity in fundamental ways, such as through the unequal
      allocation of resources across regions, development policy biased against
      pastoralism, and competition for elected political positions. Third, conflict is
      part and parcel of the adaptation process, not just an external factor inhibiting
      local adaptation strategies. Fourth, there are relative winners and losers of
      adaptation, but whether or not local adjustments to drought and conflict compound
      existing inequalities depends on power relations at multiple geographic scales
      that shape how conflicting interests are negotiated locally. Climate change
      adaptation policies are unlikely to be successful or minimize inequity unless the
      political dimensions of local adaptation are considered; however, existing power
      structures and conflicts of interests represent political obstacles to developing
      such policies.

PMID- 18726052
TI  - When has an abandoned field become a semi-natural grassland or heathland?
AB  - This study presents a meta-analysis of a collective dataset describing the
      succession from abandoned fields to semi-natural grassland and heathland
      vegetation over the past century. The study objectives were to develop a method
      for statistical discrimination between abandoned fields and semi-natural habitats
      and to analyze the probability that an abandoned field had developed into a semi
      natural habitat. A statistical classification model was developed, based on lists
      of vascular plants from 2059 plots from Danish semi-natural grasslands and
      heathlands, and abandoned fields of varying age. This model was shown to
      discriminate effectively between abandoned fields and semi-natural habitats, and
      it was found to be potentially useful for the detection of abandoned fields
      approaching semi-natural vegetation. We suggest that the model may help clarify
      restoration targets and assess biological condition in formerly cultivated areas.
      Statistical modeling revealed that succession age, period of abandonment and
      succession trajectory had significant effects on the probability that abandoned
      fields reached the semi-natural phase. Our study indicates that restoration
      projects targeting grassland and heathland should take local species pools and
      soil fertility into account.

PMID- 18726053
TI  - [Sarcopenia and whole body vibration training: an overview].
AB  - The loss of muscle mass, muscle strength and muscle endurance-capability in the
      elderly is summarized under the term 'sarcopenia'. This phenomenon is widespread
      in the older population and is a large financial burden for the health system. As
      a consequence of sarcopenia, functional and metabolic consequences occur. These
      among other things are associated with a loss of the independent lifestyle and
      the appearance of various age-related chronic diseases. An intervention with
      whole body vibration training can increase muscle strength, especially in older
      people with a low level of muscle strength, similar to resistance training. A
      strength increase is mainly attributed to improved inter- and intramuscular
      coordination. A muscle hypertrophy is also possibly realizable with people with
      low base level. A low injury-risk and the only rare appearance of side-effects
      makes whole body vibration training an interesting preventive intervention for
      older people.

PMID- 18726054
TI  - The effects of body mass index on cerebral blood flow velocity.
AB  - OBJECTIVE: Obesity is a risk factor for cerebrovascular disease. We aimed to
      determine the effects of high body mass index (BMI) on cerebral blood flow
      regulation in patients with type-2 diabetes mellitus, hypertension, and stroke.
      METHODS: We analyzed data from 90 controls, 30 diabetics, 45 hypertensives, and
      32 ischemic stroke patients who underwent transcranial Doppler for evaluation of
      blood flow velocities (BFV) in the middle cerebral arteries (MCA) and
      cerebrovascular resistance (CVR) during supine rest and head-up tilt. This study
      was a cross-sectional analysis. We used a structural equation multiple indicators
      modeling to determine the effects of BMI and other background variables (age,
      sex, race, smoking, alcohol use, and systolic blood pressure) on cerebral BFV.
      RESULTS: Higher BMI (P = 0.02) and age (P = 0.004) were associated with lower
      mean BFV during baseline, independent of diagnosis of diabetes mellitus,
      hypertension or stroke, and after adjusting for all background variables and
      vessel diameters. Men, especially those with stroke, had a lower mean BFV than
      women (P = 0.01). CVR increased with BMI (P = 0.001) at baseline and during head
      up tilt (P = 0.02), and was elevated in obese subjects (P = 0.004) compared to
      normal weight subjects across all groups. INTERPRETATION: High BMI is associated
      with a reduction in cerebral BFV and increased CVR. These findings indicate that
      obesity can adversely affect cerebral blood flow and resistance in the
      cerebrovascular bed, independent of diagnosis of type-2 diabetes, hypertension or
      stroke. Obesity may contribute to cerebromicrovascular disease, and affect
      clinical functional outcomes of the older population.

PMID- 18726055
TI  - Antibody testing as a diagnostic tool in autonomic disorders.
AB  - Some forms of peripheral autonomic dysfunction (especially enteric neuropathy and
      subacute panautonomic failure) occur as autoimmune phenomena either in isolation
      or in the context of cancer. Autoimmune autonomic ganglionopathy is an example of
      a severe, but potentially treatable, antibody-mediated form of autonomic failure.
      Diagnostic evaluation of autonomic disorders can be supplemented by testing for
      paraneoplastic antibodies and antibodies against membrane receptors. The
      diagnostic antibodies most commonly associated with dysautonomia are
      paraneoplastic antibodies (anti-Hu and CRMP-5) and ganglionic acetylcholine
      receptor antibodies.

PMID- 18726056
TI  - Reversal of tetraparesis due to staphylococcal cervical spondylodiscitis
      associated with anterior epidural abscess after conservative treatment.

PMID- 18726057
TI  - Endonasal endoscopic repair of ethmoid roof cerebrospinal fluid fistula by
      suturing the dura.
AB  - INTRODUCTION: Over the past 20years, improvement in surgical techniques as well
      advances in surgical instruments for sinus surgery has led to surgical closure of
      cerebrospinal fluid (CSF) leak using endoscopic approach. Minimally invasive and
      having lower post op morbidity, compared to traditional intracranial techniques,
      repairing CSF leak endoscopically has evolved to become the standard practice for
      management of CSF leak. DISCUSSION: Widespread use of endoscope in sinus surgery
      have made us more familiar with the anatomy of the sinuses as well as the skull
      base. In this paper, we will describe our experience of CSF repair by suturing
      dura under endoscopic guidance for the repair of small ethmoid roof (<1.2cm)
      defects.

PMID- 18726058
TI  - Adverse effects of topical papaverine on auditory nerve function.
AB  - BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to
      manage vasospasm during various neurosurgical operations. Transient cranial nerve
      dysfunction has been described in a few cases with topical papaverine. This study
      supports previous reports and provides neurophysiological evidence of an adverse
      effect on the auditory nerve. METHODS: We conducted a retrospective review of 70
      consecutive microvascular decompression operations and studied those patients who
      received topical papaverine for vasospasm. Topical papaverine was used as a
      direct therapeutic action to manage vasospasm in a total of 11 patients. The
      timing of papaverine application and ongoing operative events was reviewed
      relative to changes in neurophysiological recordings. Brainstem auditory evoked
      potentials (BAEPs) were routinely used to monitor cochlear nerve function during
      these operations. FINDINGS: A temporal relationship was found between topical
      papaverine and BAEP changes leading to complete waveform loss. The average
      temporal delay between papaverine and the onset of an adverse BAEP change was 5
      min. In 10 of 11 patients, BAEP waves II/III-V completely disappeared within 2 to
      25 min after papaverine. Eight of these 10 patients had complete loss of BAEP
      waveforms within 10 min. One patient showed no recovery of later waves and a
      delayed profound sensorineural hearing loss. The average recovery time of BAEP
      waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical
      papaverine for the treatment of vasospasm was associated with the onset of a
      transient disturbance in neurophysiological function of the ascending auditory
      brainstem pathway. The complete disappearance of BAEP waveforms with a consistent
      temporal delay suggests a possible adverse effect on the proximal eighth nerve.
      Recommendations to avoid potential cranial nerve deficits from papaverine are
      provided.

PMID- 18726059
TI  - Meningioma--an unusual cause of a forehead lump.
AB  - CASE REPORT: A patient presenting with a forehead lump secondary to an
      intraosseous meningioma is described. In addition, diagnosis and management of
      meningiomata are discussed.

PMID- 18726060
TI  - Outcome of myelomeningocoele repair in sub-Saharan Africa: the Nigerian
      experience.
AB  - OBJECTIVE: Early repair of myelomeningocoele (MM) is associated with decreased
      morbidity and mortality. In sub-Saharan Africa, the peculiar harsh economic and
      social realities make late presentation, malnutrition and sepsis at presentation
      prevalent. As these factors may affect surgical repair, the aim of this study was
      to review the outcome of repair of MM in this peculiar patient population.
      MATERIALS AND METHODS: A prospective study of patients with MM who presented at
      the Lagos State University Teaching Hospital, Lagos, Nigeria over a 12 month
      period was studied. Follow up ranged from 8 weeks to 1 year. RESULTS: Five
      patients died while awaiting surgery. Thirty-six patients, 24 males and 12 female
      infants with MM were operated on during the study period. Majority of the
      patients were operated on or after the seventh day of life. The median age at
      surgery was 11th day of life (range second day-2 years). The mean surface area of
      the myelomeningocoele was 26.4 cm(2) (range 12.6-62.9 cm(2)). The post-operative
      morbidity and mortality was five and one, respectively. CONCLUSIONS: Intracranial
      sepsis is the main cause of death in MM patients who are not operated on time.
      The patients we are seeing are probably those that survived to present at the
      hospital; by that time primary closure is usual without the need for complex
      plastic procedures. Delay in presentation even with associated malnutrition and
      local sepsis seems not to significantly affect the outcome of MM repair.

PMID- 18726061
TI  - Temporal mediobasal tumors: a proposal for classification according to surgical
      anatomy.
AB  - OBJECTIVE: Development of a classification for temporal mediobasal tumors based
      on anatomical and neuroradiological aspects to help evaluate surgical
      accessibility and risk. METHODS: Preoperative magnetic resonance imaging,
      surgical approaches and outcomes of 235 patients with a temporal mediobasal tumor
      were analyzed retrospectively. Surgical landmarks were defined in accordance with
      operative anatomy. Previous classifications of these tumors were reviewed and a
      new classification system was developed. RESULTS: The new classification system
      recognises four types of temporal mediobasal tumor based on anatomical landmarks,
      location, and size. Type A comprises lesions confined to the uncus, hippocampus,
      parahippocampus, and/or amygdala. Type B comprises lesions in the area
      immediately lateral to the structures where type A tumors are located but sparing
      lateral gyri. Type C tumors are larger lesions, which occupy the area of type A
      and type B simultaneously. Type D tumors originate from the temporal mediobasal
      region and invade into the adjacent structures of the temporal stem, insular
      cortex, claustrum, putamen, or pallidum. The area occupied by a tumor in the
      axial plane was divided into anterior (a) and posterior (p) subregions.
      Progressive grading from A to D and from "a" to "p" was based on the view that
      larger and more posteriorly growing tumors were more difficult to remove. Lesions
      located in the anterior subregion (n = 173) were easier to remove by the
      transsylvian route (39%) or after partial anterior lobectomy (32%). For the
      posterior lesions (n = 62), a subtemporal approach was more appropriate (75%).
      CONCLUSIONS: Based on a series of 235 temporal mediobasal tumors, a
      classification system was designed to aid in decision making about operability,
      surgical risk, and approach.

PMID- 18726062
TI  - Intrasellar plasmacytoma: an unusual presentation of multiple myeloma.
AB  - INTRODUCTION: Plasmacytomas are unusual causes of a sellar mass. Occasionally,
      they can be misdiagnosed as a nonfunctioning adenoma because of radiological and
      clinical similarities. LITERATURE REVIEW: We reviewed the pertinent literature
      and discuss here in the light of an illustrative case of our own. DISCUSSION: A
      70-year-old woman presented with a recurrent hypophysial mass. Initial diagnosis
      of a nonfunctioning pituitary adenoma was later overruled by a repeat biopsy,
      which showed a plasmacytoma. The tumor stained positively for CD138 and kappa
      light chain. Further studies confirmed the diagnosis of multiple myeloma. The
      patient was successfully treated with radiotherapy followed by systemic
      chemotherapy. Because they have different therapeutic implications,
      extramedullary plasmacytomas involving pituitary gland should be considered in
      the differential diagnosis of a nonfunctioning pituitary mass.

PMID- 18726064
TI  - Trigemino-cardiac reflex may be refractory to conventional management in adults.

PMID- 18726065
TI  - Outcome of cerebral amyloid angiopathic brain haemorrhage.
AB  - BACKGROUND: Abnormal amyloid protein can be deposited in the wall of cerebral
      arteries leading to fragility and intracerebral haematoma in patients with
      cerebral amyloid angiopathy. Diagnosis can be done only histologically. The
      indication of surgically treating intracerebral haemorrhage caused by amyloid
      angiopathy is controversial. There are studies showing a high mortality and a
      high rate of recurrent bleeding. Others show almost no recurrent bleeding and a
      very low mortality and a third party states that even when recurrent
      intracerebral haemorrhage occurs, re-evacuation should be performed. In the
      present retrospective study a population of 99 patients suffering from cerebral
      amyloid angiopathy-related cerebral haemorrhage has been studied, to investigate
      the surgical outcome. METHOD: Ninety-nine patients were histologically diagnosed
      with cerebral amyloid angiopathy in our department from 1991-2004. The outcome
      has been established by the Glascow Outcome Score. FINDINGS: It could be shown
      that intraventricular bleeding and age >75 years increased the mortality after
      operative evacuation. Recurrent bleeding occurred in 22% of patients. After re
      evacuation at least half of the patients survived leading to the suggestion to re
      operate a recurrent bleeding since patients have a chance to survive even when
      the Glascow Outcome Score is 3. The overall mortality in the observed population
      was 16% and 11% had a very good neurological recovery based on a Glascow Outcome
      Score of 4-5. The operative outcome in amyloid angiopathy related intracerebral
      haemorrhage is similar to this of intracerebral haemorrhage induced by other
      causes like hypertensive bleeding. CONCLUSIONS: Possible cerebral amyloid
      angiopathy is no contraindication for evacuation of brain-haematoma, and
      especially not in patients younger than 75 years old without an intraventricular
      haemorrhage.

PMID- 18726066
TI  - A "self adhering" prosthesis for hernia repair: experimental study.
AB  - BACKGROUND: Prosthetic reinforcement is now routine in the management of inguinal
      and incisional hernia, and it significantly reduces the risk of recurrence. After
      surgery, chronic pain is often attributed to the characteristics of the mesh and
      to the method of fixation in the wound, with a potential risk of nerve or muscle
      injuries. AIM: To evaluate the properties of a new "self adhering" prosthesis in
      an experimental animal study. MATERIALS AND METHODS: The self adhering
      prosthesis, a lightweight (40 mg/m(2)) polypropylene mesh coated with a synthetic
      glue on one side, was implanted laparoscopically in pigs. Removal of the
      prosthesis was performed at one day, one week and one month post operatively. A
      macroscopic and microscopic evaluation was performed. The results, using a
      quantitative score, were compared to those of a control group using the same
      polypropylene mesh without glue, but fixed by staples. RESULTS: The operative
      time was significantly lower in the self adhering group: 23 min (15-32) versus 31
      min (21-40) (P = 0.01). The average time interval from the introduction of the
      mesh into the preperitoneal space until the appearance of the first tough
      adhesion was 3 min (2-4). In the control group, the mesh handling time was 8.3
      min (5-14) (P = 0.01). At the time of implantation, the score was at a maximum
      value in all cases for the self adhering prostheses, especially concerning
      handling and adhesiveness. Upon removal, this score was noted to be good or very
      good in 90-100% of the cases. There was a good integration in the muscle
      confirmed histologically, and there was no shrinkage, no mobilisation and no
      migration. At one month, the thickness of the fibrosis at the limits of the
      meshes was significantly higher for the self adhering prostheses (P = 0.02).
      CONCLUSION: In this experimental study, the self adhering prosthesis demonstrated
      its adhesive properties and its ability to be well tolerated, with a good
      macroscopic and microscopic integration into the abdominal wound. This should
      allow us to perform a clinical prospective study in an open and laparoscopic
      approach with the double objective of reducing post operative pain induced by
      mechanical fixation and decreasing the cost of these procedures by reducing the
      operative time and by eliminating staple fixation.

PMID- 18726067
TI  - Improvement of reduced serum cartilage oligomeric matrix protein levels in
      systemic juvenile idiopathic arthritis patients treated with the anti-interleukin
      6 receptor monoclonal antibody tocilizumab.
AB  - In this study, we determined serum cartilage oligomeric matrix protein (COMP)
      levels in systemic juvenile idiopathic arthritis (sJIA) patients during both the
      active and the remission phases to investigate how the growth cartilage turnover
      changed under tocilizumab treatment. Specimens were collected from 201 healthy
      children under 16 years of age with no growth impairment, and paired sera were
      collected from 11 sJIA patients treated with tocilizumab. Disease activity was
      assessed from white blood cell count, erythrocyte sedimentation rate, C-reactive
      protein, and ferritin, and the COMP concentration was determined by sandwich
      enzyme-linked immunosorbent assay. Serum COMP concentrations were found
      independent of age, and the mean value in healthy children was 17.74+/-5.6 U/L.
      The mean serum COMP in sJIA patients during the active phase was 10.75+/-3.9 U/L,
      lower than that of healthy children. The mean serum COMP in the remission phase
      (14.89+/-3.9 U/L) was significantly higher than that in the active period
      (P<0.05). These results suggested that in sJIA patients, a reduced serum COMP
      concentration is a useful marker of active disease and growth impairment, and
      that the growth cartilage turnover suppressed during the active phase is improved
      in the remission phase under tocilizumab treatment.

PMID- 18726068
TI  - In vivo growth-inhibition of Sarcoma 180 by an alpha-(1-->4)-glucan-beta-(1-->6)
      glucan-protein complex polysaccharide obtained from Agaricus blazei Murill.
AB  - Agaricus blazei Murrill, a native mushroom of Brazil, has been widely consumed in
      different parts of the world due to its anticancer potential. This effect is
      generally attributed to its polysaccharides; however, the precise structure of
      these has not been fully characterized. To better understand the relationship
      between polysaccharide structures and antitumor activity, we investigated the
      effect of the intraperitoneally (i.p.) or orally (p.o.) administered alpha-(1-
      >4)-glucan-beta-(1-->6)-glucan-protein complex polysaccharide from A. blazei
      alone or in association with 5-fluorouracil (5-FU) in tumor growth using Sarcoma
      180 transplanted mice. Hematological, biochemical, and histopathological analyses
      were performed in order to evaluate the toxicological aspects of the
      polysaccharide treatment. The polysaccharide had no direct cytotoxic action on
      tumor cells in vitro. However, the polysaccharide showed strong in vivo antitumor
      effect. Thus, the tumor growth-inhibitory effect of the polysaccharide is
      apparently due to host-mediated mechanisms. The histopathological analysis
      suggests that the liver and the kidney were not affected by polysaccharide
      treatment. Neither enzymatic activity of transaminases (AST and ALT) nor urea
      levels were significantly altered. In hematological analysis, leucopeny was
      observed after 5-FU treatment, but this effect was prevented when the treatment
      was associated with the polysaccharide. In conclusion, this polysaccharide
      probably could explain the ethnopharmacological use of this mushroom in the
      treatment of cancer.

PMID- 18726070
TI  - The cell-cell adhesion molecule E-cadherin.
AB  - This review is dedicated to E-cadherin, a calcium-dependent cell-cell adhesion
      molecule with pivotal roles in epithelial cell behavior, tissue formation, and
      suppression of cancer. As founder member of the cadherin superfamily, it has been
      extensively investigated. We summarize the structure and regulation of the E
      cadherin gene and transcript. Models for E-cadherin-catenin complexes and cell
      junctions are presented. The structure of the E-cadherin protein is discussed in
      view of the diverse functions of this remarkable protein. Homophilic and
      heterophilic adhesion are compared, including the role of E-cadherin as a
      receptor for pathogens. The complex post-translational processing of E-cadherin
      is reviewed, as well as the many signaling activities. The role of E-cadherin in
      embryonic development and morphogenesis is discussed for several animal models.
      Finally, we review the multiple mechanisms that disrupt E-cadherin function in
      cancer: inactivating somatic and germline mutations, epigenetic silencing by DNA
      methylation and epithelial to mesenchymal transition-inducing transcription
      factors, and dysregulated protein processing.

PMID- 18726071
TI  - Differential regulation of collagen types I and III expression in cardiac
      fibroblasts by AGEs through TRB3/MAPK signaling pathway.
AB  - Advanced glycation end products (AGEs) play an important role in collagen
      deposition in diabetic cardiomyopathy. TRB3, a mammalian homolog of Drosophila
      tribbles, functions to increase glucose intolerance and regulates cell
      proliferation. We demonstrated that AGEs induce collagen type I expression but
      inhibit collagen type III expression, accompanied by increased TRB3 expression.
      Furthermore, the collagen type I induced byAGEs was down-regulated after
      inhibition of ERK and p38-MAPK, the collagen type III reduced by AGEs was up
      regulated after inhibition of ERK. The expression of collagen types I and III
      regulated by AGEs through MAPK was partly reversed after treatment with TRB3
      siRNA. It suggests that the TRB3/MAPK signaling pathway participates in the
      regulation of collagen types I and III by AGEs and may provide new therapeutic
      strategies for diabetic cardiomyopathy.

PMID- 18726072
TI  - Recombinant scorpine: a multifunctional antimicrobial peptide with activity
      against different pathogens.
AB  - Scorpine is an antimicrobial peptide whose structure resembles a hybrid between a
      defensin and a cecropin. It exhibits antibacterial activity and inhibits the
      sporogonic development of parasites responsible for murine malaria. In this
      communication we report the production of scorpine in a heterelogous system,
      using a specific vector containing its cloned gene. The recombinantly expressed
      scorpine (RScp) in (Anopheles gambie) cells showed antibacterial activity against
      (Bacillus subtilis) and (Klebsiella pneumoniae), at 5 and 10 microM,
      respectively. It also produced 98% mortality in sexual stages of (Plasmodium
      berghei) at 15 microM and 100% reduction in (Plasmodium falciparum) parasitemia
      at 5 microM. RScp also inhibited virus dengue-2 replication in C6/36 mosquito
      cells. In addition, we generated viable and fertile transgenic (Drosophila) that
      overexpresses and correctly secretes RScp into the insect hemolymph, suggesting
      that the generation of transgenic mosquitoes resistant to different pathogens may
      be viable.

PMID- 18726069
TI  - Serum amyloid A: an acute-phase protein involved in tumour pathogenesis.
AB  - The synthesis of acute-phase protein serum amyloid A (SAA) is largely regulated
      by inflammation- associated cytokines and a high concentration of circulating SAA
      may represent an ideal marker for acute and chronic inflammatory diseases.
      However, SAA is also synthesized in extrahepatic tissues, e.g. human carcinoma
      metastases and cancer cell lines. An increasing body of in vitro data supports
      the concept of involvement of SAA in carcinogenesis and neoplastic diseases.
      Accumulating evidence suggests that SAA might be included in a group of
      biomarkers to detect a pattern of physiological events that reflect the growth of
      malignancy and host response. This review is meant to provide a broad overview of
      the many ways that SAA could contribute to tumour development, and accelerate
      tumour progression and metastasis, and to gain a better understanding of this
      acute-phase reactant as a possible link between chronic inflammation and
      neoplasia.

PMID- 18726073
TI  - The discovery of alpha-Klotho and FGF23 unveiled new insight into calcium and
      phosphate homeostasis.
AB  - 1The traditional view of calcium homeostasis is that it is maintained by two
      essential reactions. First, changes in extracellular Ca2+ are sensed in several
      distinct cell types, stimulating the secretion of parathyroid hormone (PTH),
      1,25(OH)(2) D and calcitonin in response to the body's requirement. Second, these
      calcitropic hormones then act on the calcium-translocating cells of the kidney,
      bone, and intestine to restore calcium balance. Recent progress indicates that
      alpha-Klotho and fibroblast growth factor (FGF) 23 are key players that integrate
      the multi-step regulatory system of calcium homeostasis that rapidly adjusts the
      extracellular calcium concentration and continuously maintains its concentration
      within a narrow physiological range. alpha-Klotho and FGF23 are also found to be
      major players in the regulatory system of phosphate homeostasis. Here, the
      demonstration of the molecular functions of alpha-Klotho and FGF23 has recently
      given new insight into the field of calcium and phosphate homeostasis.

PMID- 18726074
TI  - Lack of complete 1p19q deletion in a consecutive series of 12 WHO grade II
      gliomas involving the insula: a marker of worse prognosis?
AB  - 1p19q codeletion in WHO grade II glioma (GIIG) is claimed to be a marker of
      better outcome and chemosensitivity. Through the molecular study of 12 insular
      GIIG, our goal was to investigate a possible anatomo-molecular relationship in
      insula, specific brain sub-region, known to be involved with high frequency in
      GIIG. Loss of heterozygosity on 1p and 19q chromosomes was assessed in all
      tumors. None complete deletion of the 1p and 19q arms chromosomes and partial
      deletions in 3 patients were retrieved in the 11 WHO grade II oligodendrogliomas
      and one oligo-astrocytoma analyzed. Discrepancy between our results and the high
      reported incidence of 1p19q codeletion in oligodendrogliomas could mean that
      insular GIIG has a specific molecular pattern. We hypothesize that prognosis of
      insular GIIG is worse than in other locations, with reduced chemosensitivity.
      Thanks to minimization of surgical risks, surgery might be a first intention
      therapeutic option proposed in the GIIG.

PMID- 18726075
TI  - Towards engineering increased pantothenate (vitamin B(5)) levels in plants.
AB  - Pantothenate (vitamin B(5)) is the precursor of the 4'-phosphopantetheine moiety
      of coenzyme A and acyl-carrier protein. It is made by plants and microorganisms
      de novo, but is a dietary requirement for animals. The pantothenate biosynthetic
      pathway is well-established in bacteria, comprising four enzymic reactions
      catalysed by ketopantoate hydroxymethyltransferase (KPHMT), L: -aspartate-alpha
      decarboxylase (ADC), pantothenate synthetase (PS) and ketopantoate reductase
      (KPR) encoded by panB, panD, panC and panE genes, respectively. In higher plants,
      the genes encoding the first (KPHMT) and last (PS) enzymes have been identified
      and characterised in several plant species. Commercially, pantothenate is
      chemically synthesised and used in vitamin supplements, feed additives and
      cosmetics. Biotransformation is an attractive alternative production system that
      would circumvent the expensive procedures of separating racemic intermediates. We
      explored the possibility of manipulating pantothenate biosynthesis in plants.
      Transgenic oilseed rape (Brassica napus) lines were generated in which the E.
      coli KPHMT and PS genes were expressed under a strong constitutive CaMV35SS
      promoter. No significant change of pantothenate levels in PS transgenic lines was
      observed. In contrast plants expressing KPHMT had elevated pantothenate levels in
      leaves, flowers siliques and seed in the range of 1.5-2.5 fold increase compared
      to the wild type plant. Seeds contained the highest vitamin content, indicating
      that they might be the ideal target for production purposes.

PMID- 18726076
TI  - Gastroprotective and anti-oxidative properties of ascorbic acid on indomethacin
      induced gastric injuries in rats.
AB  - Reactive oxygen species (ROS) have been implicated in the etiology of
      indomethacin-induced gastric mucosal damage. This study investigated ascorbic
      acid (vitamin C)'s protective effects against oxidative gastric mucosal damage
      induced by indomethacin. Ascorbic acid is a powerful antioxidant because it can
      donate a hydrogen atom and form a relatively stable ascorbyl free radical. We
      have investigated alterations in the levels of myeloperoxidase, antioxidant
      system enzymes (glutathione S-transferase, superoxide dismutase, glutathione
      reductase, catalase, glutathione peroxidase), lipid peroxidation and glutathione,
      as markers for ulceration process following oral administration of ascorbic acid,
      famotidine, lansoprazole, and ranitidine in rats with indomethacin-induced
      ulcers. In the present study, we found that (1) ascorbic acid, famotidine,
      lansoprazole and ranitidine reduced the development of indomethacin-induced
      gastric damages; (2) the administration of indomethacin caused a significant
      decrease in the levels of superoxide dismutase, glutathione peroxidase,
      glutathione S-transferase and glutathione, and an increase in the lipid
      peroxidation level; (3) the administration of ascorbic acid reversed the trend,
      inducing a significant increase of these enzymes' levels and a reduction in lipid
      peroxidation level in tissues; and (4) catalase, glutathione reductase and
      myeloperoxidase activities, increased by indomethacin, were found to be lower in
      the ascorbic acid, famotidine, lansoprazole and ranitidine-treated groups. The
      results indicate that the gastroprotective properties of ascorbic acid could be
      related to its positive effects on the antioxidant system and myeloperoxidase
      activity in indomethacin-induced gastric ulcers in rats.

PMID- 18726078
TI  - [Blood clots in erythrocyte concentrates during transfusion].
AB  - BACKGROUND: The presence of multiple blood clots in leucocyte-depleted
      erythrocyte concentrates during a transfusion gave rise to an investigation to
      find the exact cause. MATERIALS AND METHODS: Determination of the various blood
      group systems was carried out using the gel centrifugation method and also the
      polymerase chain reaction (PCR) using sequence-specific primers. In addition the
      human leucocyte antigens (HLA) class 1 and class 2 markers were determined with
      molecular biological methods. RESULTS: The erythrocytes in the blood bags
      containing the blood clots showed a mixed-field agglutination in each blood group
      where the donor and recipient had different phenotypes. The HLA groups, however,
      could be solely attributed to the patient, since during the preparation of
      erythrocyte concentrates all leucocytes are removed and only very few residual
      cells containing DNA are present. CONCLUSIONS: To the best of our knowledge, this
      is the first detailed report on blood clots from patient blood in erythrocyte
      concentrates, which occurred during a transfusion. The retrograde filling of the
      blood bag with patient blood during the transfusion led to coagulation in the
      bag. Therefore, careful attention must be taken when dealing with stored blood
      and corresponding training must be regularly carried out.

PMID- 18726077
TI  - In the rat brain acetyl-L-carnitine treatment modulates the expression of genes
      involved in neuronal ceroid lipofuscinosis.
AB  - Acetyl-L-carnitine (ALC) is a naturally occurring substance that, when
      administered at supraphysiological concentration, is neuroprotective. It is a
      molecule of considerable interest for its clinical application in various neural
      disorders, including Alzheimer's disease and painful neuropathies. Suppression
      subtractive hybridization methodology was used for the generation of subtracted
      cDNA libraries and the subsequent identification of differentially expressed
      transcripts in the rat brain after ALC treatment. The method generates an
      equalized representation of differentially expressed genes irrespective of their
      relative abundance and it is based on the construction of forward and reverse
      cDNA libraries that allow the identification of the genes which are regulated by
      ALC. We report that ALC treatment: (1) upregulates lysosomal H(+)/ATPase gene
      expression and (2) downregulates myelin basic protein gene expression. The
      expression of these genes is altered in some forms of neuronal ceroid
      lipofuscinosis (NCL) pathologies. In this case, ALC might rebalance the disorders
      underlying NCL disease represented by a disturbance in pH homeostasis affecting
      the acidification of vesicles transported to lysosomal compartment for
      degradation. This study provides evidence that ALC controls genes involved in
      these serious neurological pathologies and provides insights into the ways in
      which ALC might exert its therapeutic benefits.

PMID- 18726079
TI  - [Sedation of infants with congenital hyperinsulinism during PET CAT scanning. A
      case collection].
AB  - Infants with congenital hyperinsulinism may require a positron emission
      tomography examination with 18F-labeled L-DOPA for the evaluation and planning of
      surgical interventions. To obtain optimal results it is important for the child
      to be in a stress-free situation because a stable glucose homoeostasis must be
      maintained by intravenous glucose infusion. The infant needs to lie calm over a
      long period of time to obtain optimal results. Sedation for this purpose can be
      achieved with a continuous infusion of propofol and should be carried out by an
      anesthesiologist. Additionally blood glucose measurements must be regularly
      carried out and the glucose infusion must be adjusted to prevent hypoglycemia.

PMID- 18726080
TI  - A new bolosaurid parareptile, Belebey chengi sp. nov., from the Middle Permian of
      China and its paleogeographic significance.
AB  - A new bolosaurid parareptile, Belebey chengi sp. nov., is described from
      Dashankou, Gansu Province, China, a Middle Permian locality which is known mostly
      for its therapsid fauna. The material consists of well-preserved mandibular and
      anterior skull remains and currently represents the largest and latest surviving
      member of Bolosauridae. Phylogenetic analysis of bolosaurid interrelationships,
      the first analysis of any clade of Early Permian parareptiles, indicates that the
      new taxon groups consistently with the other (Russian) members of the genus
      Belebey, and forms the sister clade to the genus Bolosaurus from North America.
      The Early Permian Eudibamus cursoris from Germany falls into the basal most
      position within Bolosauridae. Our analysis also shows that the split between the
      main bolosaurid lineages must have occurred near or before the Permo
      Carboniferous boundary and that the paleo-equatorial region of Laurasia probably
      served as the center of origination for these parareptiles. A similar pattern can
      be found in other clades of Paleozoic amniotes, suggesting that this may be the
      general trend in early amniote evolution.

PMID- 18726081
TI  - [A new look at the corticostriatal-thalamocortical circuit in sporadic
      Parkinson's disease].
AB  - The traditional model of corticostriatal-thalamocortical projections, with
      indirect and direct pathways, provides a simplified and useful explanation for
      the motor deficits (hypokinesia, bradykinesia) that develop in the course of
      sporadic Parkinson's disease. In the classic model, major emphasis is placed on
      the dopamine deficiency in the dorsal striatum that occurs as a result of
      neuronal loss in the substantia nigra of the midbrain. Nevertheless, because the
      pathological process that underlies Parkinson's disease also involves many key
      nondopaminergic connectivities, a revised model is needed that incorporates these
      projections. The focus on damage to nondopaminergic and extranigral sites is
      becoming increasingly important for clinical practice.

PMID- 18726082
TI  - [Macrophagic myofascitis vs atypical Whipple's disease].
AB  - A 39-year-old man presented pronounced asthenia and diffuse myalgias 8 months
      after a vaccination against the tetanus toxoid. Muscle biopsy disclosed
      infiltration of the perimysium and endomysium by densely packed, PAS-positive
      macrophages. Tropheryma whippelii detection in blood and faeces allowed the
      initial assumption of atypical Whipple's disease with isolated muscle
      involvement. However, the histological detection of aluminium-containing
      macrophages by means of Morin stain immunofluorescence established the diagnosis
      of macrophagic myofascitis in an obviously asymptomatic T. whippelii carrier.

PMID- 18726083
TI  - [Diagnostic imaging of venous disease: Part I: methods in the diagnosis of veins
      and thrombosis].
AB  - Diseases of the venous system are common. A variety of diagnostic imaging methods
      are available. Of these, ultrasound with color-coded duplex sonography is the
      preferred method in the diagnosis of vein diseases, especially in patients with
      suspected deep venous thrombosis (DVT) and varicosis. Compression sonography is a
      very accurate test in the diagnosis of DVT of the lower and upper extremities in
      symptomatic patients. Still today, phlebography is an important tool in the
      diagnosis of venous diseases. Computed tomography (CT) plays an important role in
      disorders of the superior and inferior vena cava and of the iliac vein. Today,
      the role of MR venography in vein diseases is limited.

PMID- 18726084
TI  - [Scientific advances in German-language research in urology. Status report on the
      first year of the "new era of reckoning in urology"].

PMID- 18726085
TI  - Mitochondrial dysfunction and delayed hepatotoxicity: another lesson from
      troglitazone.
AB  - AIMS/HYPOTHESIS: Troglitazone was approved for treatment of type 2 diabetes
      mellitus, but by 2000 it had been removed from all world markets due to severe
      drug-induced liver injury. Even today, we still do not know how many patients
      sustained a long-term liver injury. No system is in place to acquire that
      knowledge. Regarding toxicity mechanisms, controversy persists as to which ones
      are class effects of thiazolidinediones (TZDs) and which are unique to
      troglitazone. This study aims to provide long-term outcome data and new insights
      on mechanisms of troglitazone-induced liver injury. METHODS: This case series
      reports the liver injuries sustained by eleven type 2 diabetic patients treated
      with troglitazone between 1997 and 2000. Exhaustive review of medical records was
      performed for all patients. Long-term outcomes were available for all the non
      fatal cases. A comprehensive literature review was also performed. RESULTS: Long
      term liver injury progressing to cirrhosis was identified in seven patients. All
      eleven cases had liver injury patterns consistent with troglitazone toxicity.
      Analysis of these cases and of the experimental troglitazone toxicity data points
      to mitochondrial toxicity as a central factor. The general clinical patterns of
      mitochondrial hepatotoxic events are reviewed, as are the implications for other
      members of the TZD family. CONCLUSIONS/INTERPRETATION: This analysis enables the
      liver injury induced by troglitazone to be better understood. In future cases of
      delayed drug-induced liver injury that progresses after discontinuation, the
      possibility of mitochondrial toxicity should be considered. When appropriate,
      this can then be evaluated experimentally. Such proactive investigation may
      anticipate clinical risk before a large-scale therapeutic misadventure occurs.
      Drug-induced liver injury due to mitochondrial hepatotoxins may be less
      unpredictable than has previously been surmised.

PMID- 18726086
TI  - Evaluation of insulin antibodies and placental transfer of insulin aspart in
      pregnant women with type 1 diabetes mellitus.

PMID- 18726088
TI  - Antagonist-precipitated and discontinuation-induced withdrawal in morphine
      dependent rhesus monkeys.
AB  - RATIONALE: Upon discontinuation of chronic opioid treatment, withdrawal typically
      peaks in 1-3 days and decreases markedly within 1 week; however, persistent
      physiological changes have been reported long after other signs have waned.
      OBJECTIVE: The goal of this study was to compare the discriminative stimulus,
      directly observable signs, and physiological effects of withdrawal in morphine
      treated monkeys. MATERIALS AND METHODS: Monkeys received 5.6 mg/kg/12 h morphine
      and discriminated 0.0178 mg/kg naltrexone while responding under a fixed-ratio 5
      schedule of stimulus-shock termination. Drug discrimination, behavioral
      observation, and telemetry were used to monitor the emergence of withdrawal, as
      well as any persistent changes, following discontinuation of morphine treatment.
      RESULTS: Naltrexone dose (0.001-0.032 mg/kg, s.c.) was positively related with
      indices of withdrawal. In the discrimination study, monkeys responded on the
      naltrexone lever 1-5 days following discontinuation of treatment; thereafter,
      they responded exclusively on the saline lever. After discontinuation of
      morphine, the frequency of observable signs peaked within 2-3 days and most were
      not significantly increased after 5 days. In contrast, increased heart rate and
      body temperature persisted for 14 days, returning to values obtained prior to
      discontinuation by 21 days. CONCLUSIONS: To the extent that discriminative
      stimulus effects of withdrawal in nonhumans are predictive of subjective reports
      of withdrawal in humans, these data indicate that effective treatments for opioid
      dependence must address not only the short-term subjective components of
      withdrawal but also, and perhaps more importantly, lingering behavioral and
      physiological effects that might contribute to relapse long after chronic drug
      use is discontinued.

PMID- 18726089
TI  - A new solid-phase extraction disk based on a sheet of single-walled carbon
      nanotubes.
AB  - A new kind of solid-phase extraction disk based on a sheet of single-walled
      carbon nanotubes (SWCNTs) is developed in this study. The properties of such
      disks are tested, and different disks showed satisfactory reproducibility. One
      liter of aqueous solution can pass through the disk within 10-100 min while still
      allowing good recoveries. Two disks (DD-disk) can be stacked to enrich phthalate
      esters, bisphenol A (BPA), 4-n-nonylphenol (4-NP), 4-tert-octylphenol (4-OP) and
      chlorophenols from various volumes of solution. The results show that SWCNT disks
      have high extraction ability for all analytes. The SWCNT disk can extract polar
      chlorophenols more efficiently than a C(18) disk from water solution. Unlike the
      activated carbon disk, analytes adsorbed by the new disks can be eluted
      completely with 8-15 mL of methanol or acetonitrile. Finally, the DD-disk system
      is used to pretreat 1000-mL real-world water samples spiked with BPA, 4-OP and 4
      NP. Detection limits of 7, 25, and 38 ng L(-1) for BPA, 4-OP, and 4-NP,
      respectively, were achieved under optimized conditions. The advantages of this
      new disk include its strong adsorption ability, its high flow rate and its easy
      preparation.

PMID- 18726087
TI  - [Pain therapy for the lower extremities].
AB  - Pain therapy after surgical procedures of the lower extremity is an important
      goal, whereas insufficient analgesia leads to an essential reduction of the
      patient's mobility and convalescence. If possible, regional anaesthetic and
      intrathecal procedures for pre-, intra- and postoperative analgesia should be
      used. Systemic analgesics should not be used preoperatively, whereas non-opioids
      and opioids are recommended postoperatively. Surgical options that adequately
      reduce pain are intra-articular injection of local anaesthetics alone or in
      combination with opioids and cooling and physiotherapeutic treatment regimens
      after joint procedures. There is no scientific rationale as an argument for
      inserting drains. The surgical approach depends more on the individual patient's
      anatomical characteristics. Whereas the regional analgesic regimen is more
      effective than systemic therapy, sufficient tools for pain reduction during
      surgical procedures of the lower extremity are at the orthopaedic surgeon's
      disposal, too.

PMID- 18726090
TI  - Methods for detection of GMOs in food and feed.
AB  - This paper reviews aspects relevant to detection and quantification of
      genetically modified (GM) material within the feed/food chain. The GM crop
      regulatory framework at the international level is evaluated with reference to
      traceability and labelling. Current analytical methods for the detection,
      identification, and quantification of transgenic DNA in food and feed are
      reviewed. These methods include quantitative real-time PCR, multiplex PCR, and
      multiplex real-time PCR. Particular attention is paid to methods able to identify
      multiple GM events in a single reaction and to the development of microdevices
      and microsensors, though they have not been fully validated for application.

PMID- 18726091
TI  - Sensitivity to relative disparity in early visual cortex of pigmented and albino
      ferrets.
AB  - To investigate binocular interactions as the neuronal substrate for disparity
      sensitivity in the ferret (Mustela putorius furo), we measured the effects of
      relative horizontal disparities on responses of neurons in areas 17 and 18 of the
      visual cortex. Stimulation by moving bars and sinusoidal gratings showed that
      about half of our sample in pigmented ferrets was sensitive to relative
      horizontal disparity. This also included many neurons, which were classified as
      only monocularly activated when testing either eye alone. However, the tuning
      width was about two or three times coarser (median tuning width 4 degrees of
      visual angle) than that in the cat. In albino ferrets, only 8% of the neurons in
      the early visual cortex displayed some sort of disparity-dependent binocular
      interactions, but none could be clearly identified as relative disparity-coding
      neuron.

PMID- 18726092
TI  - Paradoxical inter-hemispheric transfer after section of the cerebral commissures.
AB  - Section of the forebrain commissures blocks the normally strong transfer of
      information between the two cerebral hemispheres. Although memory for a visual or
      tactile task is restricted to one hemisphere, animals may show high level
      transfer of a motor habit, and they are typically able to use combinations of eye
      and hand which require links between the two sides of the cerebral cortex. The
      evidence for paradoxical transfer is reviewed, as well as experiments that show
      that the cerebellum is the likely route for the spared communications between the
      two sides of the brain.

PMID- 18726093
TI  - Magnetic resonance imaging of lung infections in children.
AB  - The advantages and limitations of MRI in lung infections in children have not
      been well established. This article illustrates the MRI findings in children with
      pneumonia caused by Mycoplasma pneumoniae, Streptococcus pneumoniae, and other
      pathogens. Lung parenchymal, pleural, and lymph node abnormalities are well
      characterized by MRI. Loculation of pleural fluid is detected in children with
      empyema. Contrast enhancement may be useful in the differentiation of active
      inflammation from noninflammatory changes. MRI can be particularly useful in the
      follow-up of children with chronic pulmonary diseases.

PMID- 18726094
TI  - Transport at the nanoscale: temperature dependence of ion conductance.
AB  - Temperature dependent ion conductance in nanopores is measured in a wide range of
      electrolyte concentrations and compared with molecular modeling. Single outer
      membrane protein F (OmpF) channels from E. coli are reconstituted into planar
      lipid bilayers. In qualitative agreement with the experimental data, applied
      field molecular dynamics unraveled atomistic details of the ion transport.
      Comparing the temperature dependence of the channel conductance with that of the
      bulk conductivity in the range from 0 to 90 degrees C revealed that at low salt
      concentrations the transport is mainly driven along the pore surface. Increasing
      the salt concentration saturates the surface charge transport and induces ion
      transport in the center of the nanopore. The confinement of the nanopore then
      favors the formation of ion pairs. Stepping up the temperature reduces the life
      time of the ion pairs and increases the channel conductance more than expected
      from the bulk behavior.

PMID- 18726095
TI  - Prokaryotic expression of a constitutively expressed Tephrosia villosa defensin
      and its potent antifungal activity.
AB  - Plant defensins are small, highly stable, cysteine-rich antimicrobial peptides
      produced by the plants for inhibiting a broad-spectrum of microbial pathogens.
      Some of the well-characterized plant defensins exhibit potent antifungal activity
      on certain pathogenic fungal species only. We characterized a defensin, TvD1 from
      a weedy leguminous herb, Tephrosia villosa. The open reading frame of the cDNA
      was 228 bp, which codes for a peptide with 75 amino acids. Expression analyses
      indicated that this defensin is expressed constitutively in T. villosa with leaf,
      stem, root, and seed showing almost similar levels of high expression. The
      recombinant peptide (rTvD1), expressed in the Escherichia coli expression system,
      exhibited potent in vitro antifungal activity against several filamentous soil
      borne fungal pathogens. The purified peptide also showed significant inhibition
      of root elongation in Arabidopsis seedlings, subsequently affecting the extension
      of growing root hairs indicating that it has the potential to disturb the plant
      growth and development.

PMID- 18726096
TI  - Nucleophosmin mutations in Chinese adults with acute myelogenous leukemia.
AB  - Recently, mutations in the nucleophosmin (NPM1) gene were detected in 50-60% of
      adult acute myelogenous leukemia (AML) patients, mainly with a normal karyotype.
      In this study, we detected typical NPM1 mutations (types A, B, D) in untreated
      Chinese AML patients using real-time quantitative polymerase chain reaction (RQ
      PCR) followed by sequence analysis. The detection rate of NPM1 mutations in 220
      AML patients was 16.4%, including 107 (14.2%) with the French-American-British
      (FAB) subtype M2, 43 (2.3%) with M3, and 52 (30.8%) with M4/M5. Only one case
      each with an NPM1 mutation was detected in four M0, seven M1, five M6, and two M7
      cases. Eight patients were followed up after treatment, and five patients in
      hematologic remission continued to test negative for NPM1 mutations within 2-14
      months of follow-up. Sequence analysis revealed that all the 36 positive cases
      were heterozygous for the mutation with 4-bp insertions at nt 959; the 36 cases
      included 29 (80.6%) cases with type A, four (11.1%) cases with type B, and one
      rare DD-3 mutation. We also detected two new mutations, namely, CTCG and CAAG
      insertions, named BJ-01 and BJ-02, respectively. Further, 38.9% (14/36) patients
      with NPM1 mutations simultaneously exhibited internal tandem duplications in the
      FLT3 gene, and 66.7% (22/33) patients did not express CD34. The results
      demonstrated that RQ-PCR was a reliable and sensitive method for detecting NPM1
      mutations, for screening AML, and for the quantitative analysis of minimal
      residual diseases.

PMID- 18726097
TI  - Analysis of reactivation of hepatitis B virus in the treatment of B cell non
      Hodgkin's lymphoma in Hokkaido.

PMID- 18726098
TI  - A phase II study of oxaliplatin in combination with doxorubicin as first-line
      systemic chemotherapy in patients with inoperable hepatocellular carcinoma.
AB  - PURPOSE: We designed a phase II trial of the combination with oxaliplatin and
      doxorubicin for patients with unresectable HCC to evaluate the overall response
      rate (ORR) and the toxicity. METHODS: Forty patients with inoperable, systemic
      chemotherapy naive HCC were enrolled. Finally, 32 patients received oxaliplatin
      (130 mg/m(2)) and doxorubicin (60 mg/m(2)) every 3 weeks. RESULTS: Eighty-two
      treatment cycles were administered (median 2 cycles, range 1-6). There was no
      treatment-related mortality. The ORR was 15.6% (95% CI, 3.3-28.7) with five
      partial responses. The median overall survival and median overall progression
      free survival were 31 weeks (95% CI, 22-40 weeks) and 12 weeks (95% CI, 5-19
      weeks). Nausea and peripheral neuropathy were most frequent non-hematologic
      toxicities (nausea, n = 15; peripheral neuropathy, n = 10). The most frequent
      grade 3-4 hematologic adverse event was neutropenia (14 of 82 cycles) including
      three cases of febrile neutropenia. CONCLUSIONS: The combination of oxaliplatin
      and doxorubicin showed modest activity and a tolerable toxicity profile in
      advanced HCC patients.

PMID- 18726099
TI  - Involvement of putative response regulator genes of the rice blast fungus
      Magnaporthe oryzae in osmotic stress response, fungicide action, and
      pathogenicity.
AB  - Rice blast fungus (Magnaporthe oryzae) has ten histidine kinases (HKs), one
      histidine-containing phosphotransfer protein (HPt), and three response regulators
      (RRs) as putative components of the two-component signal transduction system
      (TCS). Here, we constructed knockout mutants of two putative RR genes (MoSSK1,
      MoSKN7) and a RR homolog gene (MoRIM15) to analyze the roles of TCS in
      environmental adaptation and pathogenicity. The DeltaMossk1 strain had increased
      sensitivity to high osmolarity and decreased sensitivity to fludioxonil. The
      DeltaMoskn7 strain had slightly decreased sensitivity to fludioxonil. The
      involvement of MoSkn7 in the osmoresponse was obvious only on the DeltaMossk1
      background. These results show that MoSsk1 and MoSkn7 are major and minor
      contributors, respectively, in the high osmolarity response and fludioxonil
      action. The DeltaMossk1 strain was more osmosensitive than the predicted upstream
      HK gene disruptant Deltahik1, which shows sugar-specific high osmolarity
      sensitivity. The DeltaMossk1 and DeltaMoskn7 strains showed enhanced hyphal
      melanization, suggesting that RRs regulate hyphal melanization. MoSsk1 and
      MoRim15 are required for full virulence, because the DeltaMossk1 and DeltaMorim15
      strains exhibited reduced virulence. These results suggest that the putative RRs
      of the rice blast fungus are involved in the osmotic stress response, fludioxonil
      action, and pathogenicity.

PMID- 18726100
TI  - Analysis of manganese-regulated gene expression in the ligninolytic basidiomycete
      Ceriporiopsis subvermispora.
AB  - In this work, we explore the use of the unbiased cDNA-AFLP strategy to identify
      genes involved in Mn(2+) homeostasis in Ceriporiopsis subvermispora. In this
      ligninolytic white-rot fungus, whose genome has not yet been sequenced, three Mn
      peroxidase genes responding to Mn(2+) have been characterized. Using cDNA-AFLP to
      identify transcript-derived fragments (TDFs), a total of 37 differentially
      expressed cDNA fragments were identified by comparing band intensities among cDNA
      AFLP patterns obtained from mycelia from cultures supplemented with different
      concentrations of Mn(2+). Of 21 differentially expressed TDFs, nine were
      classified as upregulated, five as downregulated and seven as unregulated. Of
      these, six upregulated and two downregulated TDFs were selected for further
      characterization. The expected TDFs for the known Mn peroxidases were not
      isolated, but several genes encoding proteins related to protein sorting, storage
      and excretion of excess Mn(2+) were identified. Transcripts induced under Mn(2+)
      supplementation exhibited homologies to the elongation factor eEF3, a HDEL
      sequence binding protein and the ARD1 subunit of the N-acetyltransferase complex,
      among others. Overall, the results obtained in this study suggest a complex
      picture of Mn(2+) homeostasis and provide the possibility to search for common
      regulatory elements in the promoters of the novel putatively identified genes.

PMID- 18726101
TI  - Circulating E-selectin and tumor necrosis factor-alpha in extraarticular
      involvement and joint disease activity in rheumatoid arthritis.
AB  - In this cross-sectional study, we assessed the relationship between circulating
      TNF-alpha and E-selectin (sE-selectin) with extraarticular involvement and
      severity of joint disease in RA. We compared 56 patients who had RA and
      extraarticular involvement (ExRA) with a group of 84 patients with only articular
      involvement (non-ExRA). ExRA had higher circulating TNF-alpha than non-ExRA (32
      +/- 9 vs. 28 +/- 6 pg/mL, P = 0.002). sE-selectin levels did not differ between
      both groups. sE-selectin correlated with tender joint count (rho = 0.19, P =
      0.03), morning stiffness (rho = 0.19, P = 0.03), severity of pain (rho = 0.21, P
      = 0.02), disease activity (assessed by the patient) (rho = 0.21, P = 0.02), HAQ
      DI (rho = 0.29, P = 0.004), and rheumatoid factor titers (rho = 0.31, P =
      <0.001). Circulating TNF-alpha had no correlation with sE-selectin or disease
      activity. We concluded that sE-selectin correlated with severity of joint
      disease, further follow-up studies should evaluate if sE-selectin is useful as
      prognosis marker for progression of articular damage.

PMID- 18726102
TI  - Pravastatin, a 3-hydroxy-3-methyl-glutharyl coenzyme A inhibitor does not show
      pleiotropic effects in patients with systemic lupus erythematosus.

PMID- 18726103
TI  - [Introduction to the topic: instrument-based anterior chamber diagnosis].

PMID- 18726104
TI  - The role of preoperative antibiotics in the prevention of wound infection after
      day case surgery for inguinal hernia in children in Ile Ife, Nigeria.
AB  - PURPOSE: Day case surgery for inguinal hernia had been an established practice of
      the Paediatric Surgery Unit, OAUTHC, Ile Ife for about two decades. In a
      retrospective review of the practice from the same center, a high incidence of
      postoperative wound infection was noted, which was attributed to the poor
      personal hygiene of the patients. This prospective study, therefore, was
      performed to evaluate the role of a single dose of preoperative antibiotic (using
      gentamicin) in the prevention of these wound infections after day case surgery
      for inguinal hernia in children. METHODS: This was a prospective study carried
      out over a period of 8 months from 11 April 2004 to 20 December 2004. During this
      period, 88 children aged from birth to 15 years were randomized into two groups
      of equal numbers to undergo elective inguinal herniotomy. The children in the
      test group received prophylactic intravenous gentamicin, 30 min before a groin
      crease incision was made, while those in the control group did not. All patients
      were subsequently followed up for 32 days for any evidence of a wound infection.
      RESULTS: There were 104 wounds in the ratio of 50:54 in the control and test
      groups, respectively. All 54 wounds of the children who received prophylactic
      gentamicin healed primarily and without complication. Five cases of wound
      infections occurred in the control group, giving an infection rate of 4.8% (P <
      0.041). Staphylococcus aureus was the single pathogen isolated from the infected
      postherniotomy wounds and this organism was wholly sensitive to gentamicin.
      CONCLUSION: From the findings in this study, administration of preoperative
      gentamicin has a role in the prevention of wound infection after day case surgery
      for inguinal hernias in susceptible children. Preoperative intravenous gentamicin
      is therefore recommended as a prophylactic measure against wound infection after
      day case surgery for inguinal hernias in those children at risk of wound
      infection.

PMID- 18726105
TI  - Clinical implications of a slight increase in the gene dosage of MYCN in
      neuroblastoma determined using quantitative PCR.
AB  - INTRODUCTION: Recently, determining the MYCN status in neuroblastoma (NB) using
      the quantitative PCR (Q-PCR) and FISH instead of the Southern blotting (SB) has
      been recommended. In order to assess the implications of the gene dosage of MYCN
      in NB, the MYCN status was evaluated using Q-PCR on DNA extracted from small
      areas of NB specimens obtained using laser capture microdissection (LCM).
      MATERIALS AND METHODS: MYCN gene dosages (MYCN/NAGK) were determined in 63
      primary NB block samples, as well as in 243 microdissected tissues from 63
      samples using Q-PCR. In 23 of 63 cases, the MYCN gene status was evaluated using
      FISH. RESULTS: Nine block samples with the amplification of MYCN based on SB
      showed a remarkable increase of the MYCN gene dosage using Q-PCR. Twelve of 54
      block samples with no amplification of MYCN based on SB showed a slight increase
      of the MYCN gene dosage (3.56 > or == MYCN/NAGK > 1.84), and 8 of these 12 cases
      were in the advanced stage. Among these 12 cases, 1 case had several LCM areas
      with a high copy number of MYCN and several LCM areas which showed no increase of
      MYCN gene. Another case showed a slight increase in the MYCN gene dosage (3.65 <
      or == MYCN/NAGK < or == 4.82) in all LCM areas. In addition, a large number of
      cells with the MYCN gain were found using FISH in the block sample. In 2 other
      cases of 12 cases, although no LCM areas showed an increased gene dosage of MYCN,
      a small number of cells with MYCN amplification were found using FISH were found
      in the block sample. CONCLUSION: A slight increase in the gene dosage of MYCN
      detected by Q-PCR may indicate that the NB tissue contains a small number of
      cells with the MYCN amplification or a large number of cells with the MYCN gain,
      which are associated with the aggressive progression of NB.

PMID- 18726106
TI  - Retrospective review of outcome after surgical treatment of enchondromas in the
      hand.
AB  - BACKGROUND: Tumours of the skeleton of the hand are rare. While the majority of
      bone tumours are benign (89.4%), a small number show signs of malignancy (4.4%).
      Among the benign bone tumours of the skeleton of the hand, enchondromas are the
      most common, at 35-65%. METHODS: In the period from 1998 to 2005, a total of 35
      enchondromas on the hand were diagnosed at the Trauma Center Lorenz Boehler.
      These were 16 women and 19 men with an average age of 36 years (age range 16-66).
      The most common site of an enchondroma was the proximal phalanx in 17 cases,
      followed by the metacarpal bone in 8 cases and the middle phalanx in 5 cases. In
      five patients, an enchondroma was found in the carpal bones. Twenty-nine patients
      underwent surgery. RESULTS: The follow-up findings (average follow-up time, 47
      months) were assessed in accordance with the formula outlined by Wilhelm and
      Feldmaier. Twenty-five of 27 patients who underwent follow-up examination showed
      an excellent result. In two patients, the result was assessed as good on account
      of restricted mobility caused by increased scar formation. No recurrence was
      detected in X-ray controls. CONCLUSION: Enchondromas of the hand are usually
      detected after a bagatelle trauma. For accurate diagnosis, conventional X-ray
      examination and if necessary, a contrast medium MRI should be performed.
      Histological investigation is compulsory due to the risk of malignancy. Depending
      on its spread, the defect in the extirpation cavity should be filled with
      autogenous spongy bone.

PMID- 18726107
TI  - The use of plasmapheresis for rapid hormonal control in severe hyperthyroidism
      caused by a partial molar pregnancy.
AB  - INTRODUCTION: The hormone human chorionic gonadotropin (hCG), secreted by molar
      tissue, is structurally similar to thyroid-stimulating hormone (TSH).
      Hyperthyroidism in trophoblastic disease is thought to be the result of TSH
      receptor activation by extremely elevated levels of hCG. Significant elevations
      in hCG levels are less common in cases of partial moles. MATERIALS AND METHODS:
      We describe a patient with partial molar pregnancy in which the levels of hCG and
      thyroid hormones were significantly high. It was not possible to decrease the
      elevated thyroid hormone concentrations to safer levels using medical treatment
      strategies only. Since the patient's vaginal bleeding increased gradually,
      plasmapheresis was used to rapidly control the thyroid hormones during the
      preoperative preparation of the patient for anesthesia and surgery. After the
      evacuation of the molar tissue, the levels of the thyroid hormones detected after
      the plasmapheresis started to decrease even further. CONCLUSION: Plasmapheresis
      may be used as an alternative to antithyroid medication for the rapid control of
      thyroid hormones in cases of severe hyperthyroidism caused by molar pregnancy.

PMID- 18726108
TI  - Primary malignant melanoma of the cervix: report of a case.
AB  - BACKGROUND: To present a case of primary malignant melanoma of the cervix. CASE:
      The patient was admitted with the complaint of vaginal bleeding. Gynecological
      examination revealed a dark, papillary mass on the posterior lip of the cervix.
      Histopathology showed a malignant neoplasm with increased vascularity, indicating
      the possibility of a primary uterine cervical melanoma. Diagnosis of malignant
      melanoma was confirmed with immunohistochemistry, which showed diffuse positive
      reactions for S-100 protein and HBM-45, with no reaction for epithelial markers,
      namely cytokeratin AE1/AE3 and epithelial membrane antigen. An extensive search
      for a melanotic lesion in skin and in uveal tract was performed to verify the
      distinct site of melanoma. The tumor was stage IB1 according to the International
      Federation of Gynecology and Obstetrics classification.The patient underwent
      radical Wertheim-Meigs hysterectomy, bilateral salpingo-oopherectomy, and
      retroperitoneal pelvic lympadenectomy. Radiotherapy or chemotherapy was not
      performed in the postoperative period. She is now free of the disease 10 months
      after the operation. CONCLUSION: Primary malignant melanoma of the cervix is a
      rare cervical malignancy.

PMID- 18726109
TI  - Acute pancreatitis: a rare cause of acute abdomen in pregnancy.
AB  - Pancreatitis in pregnancy is rare and occurs in approximately 1 in 1,000 to 1 in
      10,000 births. Acute pancreatitis rarely complicates pregnancy, can occur during
      any trimester but over half (52%) occur during the third trimester and rarely
      during post-partum period. A case of idiopathic pancreatitis in pregnancy has
      been reported. Pancreatitis often presents as an acute abdomen and can have
      lethal effect on the mother and the fetus.

PMID- 18726110
TI  - Fetal therapy in twin reserve arterial perfusion sequence pregnancies with
      alcohol ablation or bipolar cord coagulation.
AB  - OBJECTIVE: We aimed to evaluate perinatal outcome of seven pregnancies with twin
      reserve arterial perfusion sequence. MATERIALS AND METHODS: Study group included
      seven cases of acardiac twins. Out of seven acardiac twins, two cases were
      followed without interventions. We performed four alcohol ablation and one
      bipolar coagulation. For alcohol ablation, a 20-gauge needle guided with color
      Doppler USG was directed to abdominal insertion site of the single umbilical
      artery of the acardiac twin, and 1.0-2.0 mL of absolute alcohol was injected. For
      bipolar coagulation of the umbilical cord, we used 3.5 mm laparoscopic trocar and
      3.0 mm bipolar forceps. The procedures were performed under the guidance of
      transabdominal ultrasonography. RESULTS: Gestational age of the cases at
      diagnosis and at delivery was 15-32 and 17-38 weeks, respectively. Two cases
      without intervention were lost at 17 and 32 weeks. The mean time of procedure for
      bipolar coagulation and alcohol ablation were 30 and 10 min, respectively. One of
      the four cases of alcohol ablation group was aborted although alcohol ablation
      was successful. Another one case was aborted after alcohol ablation due to lost
      of fetal cardiac activity of the pump fetus. In two other cases, umbilical cord
      ablation with alcohol was successful, and they delivered live birth at 36 and 38
      weeks. In one case, we performed bipolar cord coagulation successfully, and the
      case delivered live birth at 39 weeks. The overall survival rate for intrauterine
      surgery was 60% (N 3/5). CONCLUSION: In twin reserve arterial perfusion sequence
      pregnancies with findings of poor prognosis, alcohol ablation or bipolar cord
      coagulation as fetal therapy under the guidance of ultrasonography can be done
      successfully, and should be offered as a choice to families upon discussion of
      intervention or follow-up with own complications.

PMID- 18726111
TI  - Plantar flexion: an effective training for peripheral arterial disease.
AB  - This study examined whether a training intervention likely to elicit adaptations
      in the leg could result in reduced leg pain and increased whole body physical
      capacity. Twenty-seven peripheral arterial disease (PAD) patients were randomized
      to either an individual leg plantar flexion training group (TG) training 4 x 4
      min intervals at 80% of maximal work rate three times per week for 8 weeks or a
      control group. The TG significantly increased plantar flexion peak oxygen uptake
      and power output by 23.5 and 43.9%, respectively. Treadmill peak oxygen uptake
      (VO(2peak)) significantly increased 12.3% in the TG and was associated with a
      significant increased time to exhaustion of 20.0% when treadmill walking. Eleven
      of 14 patients no longer reported leg pain limitations at VO(2peak). No
      differences in cardiac output measured at VO(2peak), or walking economy were
      observed. Plantar flexion training was effective in increasing VO(2peak) and
      walking performance, and may be a useful strategy in treatment of PAD.

PMID- 18726112
TI  - Minimally invasive video-assisted subtotal parathyroidectomy with thymectomy for
      secondary hyperparathyroidism.
AB  - BACKGROUND: Secondary hyperparathyroidism (sHPT) is common in patients with
      chronic renal failure. Bilateral cervical exploration is optimal for patients
      with sHPT. The aims of this clinical trial are to evaluate the feasibility of
      video-assisted subtotal parathyroidectomy as an alternative surgical treatment
      for sHPT. METHODS: This prospective study included 12 consecutive patients with
      sHPT. Surgical indications included a high intact parathormone level, enlarged
      parathyroid glands, high bone turnover and conditions refractory to medical
      treatment of hypercalcemia and hyperphosphatemia. RESULTS: All patients underwent
      minimally invasive video-assisted subtotal parathyroidectomy and trans-cervical
      thymectomy. Four cervical glands were found in all patients and intrathymic
      glands were identified in three (25%) patients. CONCLUSION: Minimally invasive
      video-assisted subtotal parathyroidectomy offers an alternative method, and this
      technique can be performed safely for sHPT.

PMID- 18726113
TI  - A shotgun phosphoproteomics analysis of embryos in germinated maize seeds.
AB  - To better understand the role that reversible protein phosphorylation plays in
      seed germination, we initiated a phosphoproteomic investigation of embryos of
      germinated maize seeds. A total of 776 proteins including 39 kinases, 16
      phosphatases, and 33 phosphoproteins containing 36 precise in vivo
      phosphorylation sites were identified. All the phosphorylation sites identified,
      with the exception of the phosphorylation site on HSP22, have not been reported
      previously (Lund et al. in J Biol Chem, 276, 29924-29929, 2001). Assayed with QRT
      PCR, the transcripts of ten kinase genes were found to be dramatically up
      regulated during seed germination and those of four phosphatase genes were up
      regulated after germination, which indicated that reversible protein
      phosphorylation occurred and complex regulating networks were activated during
      this period. At least one-third of these phosphoproteins are key components
      involved in biological processes which relate to seed germination, such as DNA
      repair, gene transcription, RNA splicing and protein translation, suggesting that
      protein phosphorylation plays an important role in seed germination. As far as we
      know, this is the first phosphoproteomic study on a monocot and it will lay a
      solid foundation for further study of the molecular mechanisms of seed
      germination and seedling development.

PMID- 18726115
TI  - Effectiveness of pamidronate in severe neonatal hypercalcemia caused by
      subcutaneous fat necrosis: a case report.
AB  - Subcutaneous fat necrosis of the newborn (SCFN) is a panniculitis that develops
      in fatty areas during the first weeks of life after foetal distress or perinatal
      complications. Prognosis is generally good with complete regression, but it can
      be complicated by metabolic abnormalities like hypoglycemia,
      hypertriglyceridemia, thrombocytopenia, and also potentially life-threatening
      hypercalcemia. We report a case of severe hypercalcemia complicating SCFN in a
      newborn who was treated with hyperhydration, furosemide, prednisone, and
      pamidronate.

PMID- 18726114
TI  - The endometrial hyperplasias revisited.
AB  - The proliferating lesions in the endometrium form a morphological continuum
      extending from benign to malignant, through a transitional pre-invasive stage.
      Within this spectrum, several classifications of endometrial hyperplasia have
      been developed over the years in which the precancerous lesions gained a
      substantial distinction, although not without inconsistencies in definitions and
      terminology. The revised WHO 1994 classification explicitly recognizes
      cytological atypia as the defining feature for distinguishing genuine
      hyperplastic lesions (simple and complex endometrial hyperplasia) from those that
      are potentially precancerous (simple and complex atypical endometrial
      hyperplasia) and puts an end to the verbal anarchy by adopting a common language
      of communication. This taxonomy, however, was criticized for complexity and low
      level of reproducibility. Thus, in the name of improved reproducibility a new
      classification was recently proposed which (a) combines simple and complex
      endometrial hyperplasia within one diagnostic category known as endometrial
      hyperplasia and (b) defines new criteria for recognising the precancerous
      lesions: a monoclonal growth, known as endometrial intraepithelial neoplasia
      (EIN), comprising clusters of crowded glands, greater than 1 mm in diameter,
      having a cytologically altered epithelium. The EIN concept was challenged of not
      being independently tested and received with great enthusiasm by some scholars
      and relative skepticism by others.

PMID- 18726116
TI  - Loss of PTEN function may account for reduced proliferation pathway sensitivity
      to LY294002 in human prostate and bladder cancer cells.
AB  - PURPOSE: Inhibition of phosphoinositide 3 (PI3)-kinase pathway is attractive for
      cancer treatment. To examine the role of the phosphatase and tensin homolog
      (PTEN) in the development of resistance to the treatment. METHODS: We cultured
      human prostate cancer cells (DU145 and PC-3 cells) and bladder cancer cells (EJ-1
      and UM-UC-3 cells) with a PI3-kinase inhibitor, LY294002 for more than 6 weeks
      and cell proliferation was studied. Activation of Akt1 and ERK was examined by
      immunoblotting. We introduced the wild type PTEN in UM-UC-3 cells and their
      proliferation along with the signaling pathways was also examined. RESULTS: After
      6 weeks, proliferation pathway sensitivity to LY294002 was reduced in cells
      expressing PTEN, but not in PTEN-null cells. PD98059, a MAPK/ERK kinase
      inhibitor, significantly inhibited proliferation of PTEN-expressing cells, but
      not PTEN-null cells. Stable PTEN expression in PTEN-null UM-UC-3 cells increased
      serum-induced ERK activation and sensitivity to PD98059-treatment, and reduced
      sensitivity to LY294002 after 6 weeks of exposure. CONCLUSIONS: Loss of PTEN
      function may protect against resistance to PI3-kinase inhibitors through an
      addiction to the PI3-kinase/Akt pathway.

PMID- 18726117
TI  - EGFR R497K polymorphism is a favorable prognostic factor for advanced lung
      cancer.
AB  - INTRODUCTION: It has been reported that the R497K polymorphism of the epidermal
      growth factor receptor (EGFR) gene has attenuated functions in ligand binding,
      tyrosine kinase activation, and growth stimulation. On other hand, EGFR gene
      mutations at kinase domain in non-small cell lung cancer (NSCLC) have been
      examined for their ability to predict sensitivity to gefitinib or erlotinib.
      MATERIALS AND METHODS: We investigated the EGFR mutations and/or R497K
      polymorphism statuses in 225 surgically treated NSCLC cases. 192 adenocarcinoma
      cases were included. The presence or absence of EGFR polymorphism of exon 13 was
      analyzed by PCR-RFLP method. RESULTS: EGFR mutations at kinase domain were found
      from 95 of 225 lung cancer patients. In 86.2% of patients, homo- or heterozygous
      Lys497 allele was present. No correlation existed between R497K EGFR genotype and
      clinico-pathological features, such as gender, smoking status, and pathological
      subtypes. CONCLUSIONS: EGFR mutation status was not correlated with R497KEGFR
      genotype of lung cancers. In node-negative patients, R497KEGFR genotype was not
      correlated with disease outcome. In node-positive patients, however, R497K EGFR
      was significantly associated with better overall survival. This association was
      attributable to neo-adjuvant or adjuvant chemotherapy. In 46 total gefitinib
      treated NSCLC patients, the prognosis was not different between the EGFR wild
      type (GG) patients and AG+AA patients. R497KEGFR polymorphism might be associated
      with favorable prognosis of advanced lung cancers and correlated with
      chemosensitivity.

PMID- 18726118
TI  - Gender influences monoallelic expression of ATP10A in human brain.
AB  - Human chromosome 15q11-13 and the syntenic region of mouse chromosome 7 contain
      multiple imprinted genes necessary for proper neurodevelopment. Due to
      imprinting, paternal 15q11-13 deficiencies lead to Prader-Willi syndrome (PWS)
      while maternal 15q11-13 deficiencies cause Angelman syndrome (AS). The mechanisms
      involved in parental imprinting of this locus are conserved between human and
      mouse, yet inconsistencies exist in reports of imprinting of the maternally
      expressed gene Atp10a/ATP10A. Excess maternal 15q11-13 dosage often leads to
      autism-spectrum disorder therefore further investigation to characterize the true
      imprinting status of ATP10A in humans was warranted. In this study, we examined
      allelic expression of ATP10A transcript in 16 control brain samples, and found
      that 10/16 exhibited biallelic expression while only 6/16 showed monoallelic
      expression. Contrary to the expectation for a maternally expressed imprinted
      gene, quantitative RT-PCR revealed significantly reduced ATP10A transcript in
      Prader-Willi syndrome brains with two maternal chromosomes due to uniparental
      disomy (PWS UPD). Furthermore, a PWS UPD brain sample with monoallelic ATP10A
      expression demonstrated that monoallelic expression can be independent of
      imprinting. Investigation of factors that may influence allelic ATP10A expression
      status revealed that gender has a major affect, as females were significantly
      more likely to have monoallelic ATP10A expression than males. Regulatory
      sequences were also examined, and a promoter polymorphism that disrupts binding
      of the transcription factor Sp1 also potentially contributes to allelic
      expression differences in females. Our results show that monoallelic expression
      of human ATP10A is variable in the population and is influenced by both gender
      and common genetic variation.

PMID- 18726119
TI  - Molecular heterogeneity of tumor endothelium.
AB  - Tumors depend on a vascular supply for their growth. Tumor blood vessels, which
      are derived from normal tissue vasculature, display a markedly abnormal
      phenotype. Tumor endothelial properties are highly varied in space and time. An
      important goal is to delineate the range of phenotypes in tumor endothelium and
      to identify tumor endothelial-specific molecular signatures. This information
      should lead to a more complete understanding of the mechanisms of tumor growth,
      the discovery of new therapeutic targets, and the development of biomarkers for
      diagnosis and surveillance. The goals of this review are to outline recent
      advances in dissecting tumor endothelial-cell-specific gene expression, to
      address mechanisms of phenotypic heterogeneity in tumor vascular beds, and to
      discuss the therapeutic implications of these findings.

PMID- 18726120
TI  - Changes in distribution of basic nuclear proteins and chromatin organization
      during spermiogenesis in the greater bandicoot rat, Bandicota indica.
AB  - Male germ cells of the greater bandicoot rat, Bandicota indica, have recently
      been categorized into 12 spermiogenic steps based upon the morphological
      appearance of the acrosome and nucleus and the cell shape. In the present study,
      we have found that, in the Golgi and cap phases, round spermatid nuclei contain
      10-nm to 30-nm chromatin fibers, and that the acrosomal granule forms a huge cap
      over the anterior pole of nucleus. In the acrosomal phase, many chromatin fibers
      are approximately 50 nm thick; these then thickened to 70-nm fibers and
      eventually became 90-nm chromatin cords that are tightly packed together into
      highly condensed chromatin, except where nuclear vacuoles occur.
      Immunocytochemistry and immunogold localization with anti-histones, anti
      transition protein2, and anti-protamine antibodies suggest that histones remain
      throughout spermiogenesis, that transition proteins are present from step 7
      spermatids and remain until the end of spermiogenesis, and that protamines appear
      at step 8. Spermatozoa from the cauda epididymidis have been analyzed by acid
      urea Triton X-100 polyacrylamide gel electrophoresis for basic nuclear proteins.
      The histones, H2A, H3, H2B, and H4, transitional protein2, and protamine are all
      present in sperm extracts. These findings suggest that, in these sperm of unusual
      morphology, both transition proteins and some histones are retained, a finding
      possibly related to the unusual nuclear form of sperm in this species.

PMID- 18726121
TI  - Monitoring of activated sludge settling ability through image analysis:
      validation on full-scale wastewater treatment plants.
AB  - In recent years, a great deal of attention has been focused on the research of
      activated sludge processes, where the solid-liquid separation phase is frequently
      considered of critical importance, due to the different problems that severely
      affect the compaction and the settling of the sludge. Bearing that in mind, in
      this work, image analysis routines were developed in Matlab environment, allowing
      the identification and characterization of microbial aggregates and protruding
      filaments in eight different wastewater treatment plants, for a combined period
      of 2 years. The monitoring of the activated sludge contents allowed for the
      detection of bulking events proving that the developed image analysis methodology
      is adequate for a continuous examination of the morphological changes in
      microbial aggregates and subsequent estimation of the sludge volume index. In
      fact, the obtained results proved that the developed image analysis methodology
      is a feasible method for the continuous monitoring of activated sludge systems
      and identification of disturbances.

PMID- 18726122
TI  - [Addition is also a disease].

PMID- 18726123
TI  - [PTSD and chronic pain: development, maintenance and comorbidity--a review].
AB  - In addition to posttraumatic stress disorder (PTSD) many traumatized individuals
      also suffer from chronic pain. Understanding the development and maintenance of
      these two disorders and how they interact is of crucial importance for treatment.
      This article provides an overview of the current literature on mechanisms of
      development, maintenance and comorbidity of PTSD and chronic pain. Moreover the
      perpetual avoidance model and its implications for practical application are
      presented.

PMID- 18726125
TI  - ESJ: Expert comment on Number and cost of claims linked to minor cervical trauma.

PMID- 18726124
TI  - Intra- and inter-observer reliability of determining radiographic sagittal
      parameters of the spine and pelvis using a manual and a computer-assisted
      methods.
AB  - Sagittal imbalance is a significant factor in determining clinical treatment
      outcomes in patients with deformity. Measurement of sagittal alignment using the
      traditional Cobb technique is frequently hampered by difficulty in visualizing
      landmarks. This report compares traditional manual measurement techniques to a
      computer-assisted sagittal plane measurement program which uses a radius arc
      methodology. The intra and inter-observer reliability of the computer program has
      been shown to be 0.92-0.99. Twenty-nine lateral 90 cm radiographs were measured
      by a computer program for an array of sagittal plane measurements. Ten
      experienced orthopedic spine surgeons manually measured the same parameters
      twice, at least 48 h apart, using a digital caliper and a standardized
      radiographic manual. Intraclass correlations were used to determine intra- and
      interobserver reliability between different manual measures and between manual
      measures and computer assisted-measures. The inter-observer reliability between
      manual measures was poor, ranging from -0.02 to 0.64 for the different sagittal
      measures. The intra-observer reliability in manual measures was better ranging
      from 0.40 to 0.93. Comparing manual to computer-assisted measures, the ICC ranged
      from 0.07 to 0.75. Surgeons agreed more often with each other than with the
      machine when measuring the lumbar curve, the thoracic curve, and the spino-sacral
      angle. The reliability of the computer program is significantly higher for all
      measures except for lumbar lordosis. A computer-assisted program produces a
      reliable measurement of the sagittal profile of the spine by eliminating the need
      for distinctly visible endplates. The use of a radial arc methodology allows for
      infinite data points to be used along the spine to determine sagittal
      measurements. The integration of this technique with digital radiography's
      ability to adjust image contrast and brightness will enable the superior
      identification of key anatomical parameters normally not available for
      measurement on traditional radiographs, improving the consistency of sagittal
      measurement.

PMID- 18726126
TI  - Cemento-osseous dysplasia, a radiological mimic of periapical dental abscess.
AB  - In the imaging evaluation of Emergency Department patients presenting with facial
      pain, there is a condition that can mimic the radiographic appearance of a
      periapical dental abscess. This condition, cemento-osseous dysplasia, may appear
      similar on dental X-rays, panoramic radiographs, and computed tomography
      examinations to and must be distinguished from the more common periapical abscess
      in order to avoid inappropriate intervention. This review highlights the easy
      confusion of these two entities based on radiographic appearance and the clinical
      implications of such a mistake and suggests some approaches to avoid this error.

PMID- 18726127
TI  - Abdominal pain: a presentation of a vena cava aplasia complicated by thrombosis.
AB  - This case report describes a young man presenting with iliac fossa pain secondary
      to iliac vein thrombus due to inferior vena cava aplasia. No other identifiable
      risk factor or cause for deep vein thrombosis was demonstrated.

PMID- 18726128
TI  - Monitoring growth phase-related changes in phosphatidylcholine-specific
      phospholipase C production, adhesion properties and physiology of Bacillus cereus
      vegetative cells.
AB  - The physiological status and metabolic heterogeneity of Bacillus cereus cells
      within a culture during an 8-h batch fermentation process was measured using flow
      cytometry (FCM). Concurrently, production of the toxin, PC-PLC, and the extent of
      cell adhesion of live and dead cells were monitored using novel fluorescent
      assays. Flow cytometry analysis detected growth phase-related changes in the
      physiological profiles of cells over the course of the fermentation, with
      variation in the percentage of cells displaying membrane damage and intracellular
      esterase and redox activities. As the exponential phase proceeded, populations
      became more uniform in terms of protein content as measured using FCM in tandem
      with a cell tracking dye, with the majority of cells becoming membrane intact,
      esterase positive and redox active. PC-PLC activity appeared strongly related to
      cell density. Permeabilisation of cells was accompanied by a loss in adherent
      properties, while 25-100% of cells with intracellular esterase activity possessed
      adhesion properties. Cells in late exponential phase appeared to have reduced
      adherence properties compared to cells in early exponential or lag phase. As well
      as demonstrating the utility of FCM for measuring heterogeneity in terms of cell
      physiological status throughout the course of batch cultures, the methods
      utilised in this study could be used to relate processes such as toxin production
      or cell adhesion to cell physiological state.

PMID- 18726129
TI  - Matched pair analyses of stage IV breast cancer with or without resection of
      primary breast site.
AB  - BACKGROUND: Reports demonstrate improved survival of stage IV breast cancer
      patients with primary cancer resection. This may result from selection for
      surgery, rather than biological processes. METHODS: We performed matched-pair
      analysis that minimized potential bias in selecting surgery for primary cancer.
      Chart review was also performed of 5-year survivors to assess selection bias
      affecting breast surgery. RESULTS: 19,464 breast cancer patients were identified;
      808 (4.2%) were stage IV: 622 were analyzed after eliminating wrong diagnoses or
      staging, and limiting patients to Massachusetts residents. Matched-pair analysis
      narrowed or eliminated apparent survival benefit associated with primary site
      surgery in several comparisons. When the impact of the sequence of systemic and
      surgical treatments was studied in stage IV patients, 90% 2-year survival
      occurred in patients receiving chemotherapy first, in contrast to receiving
      chemotherapy simultaneously with or after surgery, suggesting selection for
      delayed surgery after excellent response to initial chemotherapy. In bone
      metastases, the 2-year survival advantage occurred with chemotherapy before
      surgery; no difference in survival with or without surgery occurred when these
      treatments were simultaneous. Among 5-year survivors, frequency of primary site
      surgery after excellent response to systemic therapy, breast surgery in stage III
      patients incorrectly classified as stage IV, and frequency of oligo metastases
      all indicated selection bias. CONCLUSIONS: Case selection bias in primary breast
      cancer resection in state IV patients may explain most, if not all, the apparent
      survival advantage of such surgery.

PMID- 18726130
TI  - Personal genomics and genome-wide association studies: novel discoveries but
      limitations for practical personalized medicine.

PMID- 18726132
TI  - Letter to the editor--Early ERCP for gallstone pancreatitis: for whom and when?:
      Behrns KE, Ashley WS, Hunter JG, Carr-Locke DC, J Gastroenterol Surg 2008;12:629
      633.

PMID- 18726131
TI  - Neural progenitor cell-mediated delivery of interferon beta improves
      neuroblastoma response to cyclophosphamide.
AB  - BACKGROUND: We have shown that continuous systemic delivery of interferon beta
      (IFN-beta) remodels dysfunctional tumor vasculature, thereby improving tumor
      perfusion and enhancing delivery and efficacy of chemotherapeutic drugs. We
      hypothesized that because of their inherent tumor tropism, neural progenitor
      cells (NPCs) engineered to express IFN-beta could also effect maturation of tumor
      vasculature without generating high systemic levels of IFN-beta. METHODS: Mice
      with luciferase-expressing disseminated human neuroblastoma were divided into
      four groups of equal tumor burden by bioluminescence imaging: (1) untreated
      controls; (2) NPC-IFN-beta only; (3) cyclophosphamide (CTX) only; and (4) NPC-IFN
      beta in combination with CTX. Two million NPC-IFN-beta cells were administered
      twice, 7 days apart, starting 21 days after tail vein administration of tumor
      cells. CTX was administered every 6 days for three doses. Mice were killed at 6
      weeks, livers and kidneys weighed, and tumor removed for immunohistochemical
      staining for endothelial cells (CD34), pericytes (alpha-SMA), apoptosis (TUNEL
      [terminal deoxynucleotidyl transferase dUTP nick-end labeling]), and diI-labeled
      NPCs. RESULTS: Fluorescent-labeled NPCs confirmed localization of these cells to
      tumors. The alpha-SMA/CD34 ratio, a marker for vascular maturation, greatly
      increased in NPC-IFN-beta-treated tumors compared with controls. Bioluminescent
      signal from luciferase-expressing tumor cells, reflecting tumor burden, was lower
      with combination therapy than control or either monotherapy, and combination
      therapy resulted in far less tumor burden by weight in the kidneys and liver.
      CONCLUSIONS: Targeted delivery of IFN-beta with NPCs produced low circulating
      levels of IFN-beta, yet the maturing effect on the tumor vasculature and the
      enhanced efficacy of adjuvant therapy was maintained. Thus, combination therapy
      of NPC-IFN-beta with CTX warrants further investigation for the treatment of high
      risk neuroblastoma patients.

PMID- 18726133
TI  - Who should do NOTES? Initial endoscopic performance of laparoscopic surgeons
      compared to gastroenterologists and untrained individuals.
AB  - INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) is a
      multidisciplinary surgical technique. If conventional endoscopic instrumentation
      can be easily mastered, surgeons with laparoscopic experience could head NOTES
      interventions. MATERIALS AND METHODS: Thirty individuals were tested for
      endoscopic dexterity. Group 1 included seven gastroenterologists, group 2
      included 12 laparoscopically experienced surgeons lacking endoscopic experience,
      and group 3 included 11 interns who had no hands-on endoscopic or surgical
      experience. Each individual repeated an easy (T1), medium (T2), and difficult
      (T3) task ten times with endoscopic equipment on a NOTES skills-box. RESULTS:
      Group 3 had significantly poorer performances for all three tasks compared to the
      other groups. No significant differences were seen between groups 1 and 2 for T1
      and T2. The initial T3 performance of group 1 was better than that of group 2,
      but their performance after repetition was not statistically different. Groups 2
      and 3 improved significantly with repetition, and group 2 eventually performed as
      well as group 1. CONCLUSIONS: The data indicate that laparoscopic surgeons
      quickly learned to handle the endoscopic equipment. This suggests that a lack of
      endoscopic experience does not handicap laparoscopic surgeons when performing
      endoscopic tasks. Based on their knowledge of anatomy and the complication
      management acquired during surgical education, surgeons are well equipped to take
      the lead in interdisciplinary NOTES collaborations.

PMID- 18726134
TI  - Preoperative biliary drainage in patients with obstructive jaundice: history and
      current status.
AB  - RATIONALE: Preoperative biliary drainage (PBD) has been introduced to improve
      outcome after surgery in patients suffering from obstructive jaundice due to a
      potentially resectable proximal or distal bile duct/pancreatic head lesion. In
      experimental models, PBD is almost exclusively associated with beneficial
      results: improved liver function and nutritional status; reduction of systemic
      endotoxemia; cytokine release; and, as a result, an improved immune response.
      Mortality was significantly reduced in these animal models. Human studies show
      conflicting results. FINDINGS: For distal obstruction, currently the "best
      evidence" available clearly shows that routine PBD does not yield the appreciated
      improvement in postoperative morbidity and mortality in patients undergoing
      resection. Moreover, PBD harbors its own complications. However, most of the
      available data are outdated or suffer from methodological deficits. CONCLUSION:
      The highest level of evidence for PBD to be performed in proximal obstruction, as
      well as over the preferred mode, is lacking but, nevertheless, assimilated in the
      treatment algorithm for many centers. Logistics and waiting lists, although
      sometimes inevitable, could be factors that might influence the decision to opt
      for PBD, as well as an extended diagnostic workup with laparoscopy (on
      indication) or scheduled preoperative chemotherapy.

PMID- 18726136
TI  - Externally provoked freezing of gait in open runways in advanced Parkinson's
      disease results from motor and mental collapse.
AB  - Freezing of gait (FOG) in Parkinson's disease (PD) is defined as a sudden
      inability to maintain effective stepping movements. However, its pathophysiology
      remains unclear. The objectives are: (1) To assess the contribution of both
      spatial (walking speed, stride length) and temporal parameters (cadence, stride
      time) and their coefficients of variation to the genesis of FOG in PD. (2) To
      evaluate whether and how externally imposed modifications of self-determined gait
      would elicit FOG. We included ten patients with advanced PD, and with daily off
      drug FOG episodes. We focused on walking in an open runway. For each subject, we
      manipulated gait by externally imposing four changes in walking speed and four
      changes in cadence. FOG episodes, often with a long duration of more than 5-s,
      were observed mostly under conditions with a high imposed cadence. The steps that
      immediately preceded these episodes were mainly characterized by an increase in
      cadence and an increase in stride length variability. The results also underscore
      that FOG can be elicited in a laboratory setting when patients are placed under
      considerable strain, at least in advanced stages of PD. Patients were unable to
      adequately negotiate the extreme imposed cadence condition, and this resulted in
      frequent FOG episodes, even while walking in an open runway. Placing advanced PD
      patients into extreme imposed conditions leads to a motor wise and mental
      collapse response, culminating in FOG. Future work should establish the relevance
      of these findings for the more common forms of FOG, including brief episodes
      during turning or gait initiation.

PMID- 18726137
TI  - Physical activity, exercise, depression and anxiety disorders.
AB  - There is a general belief that physical activity and exercise have positive
      effects on mood and anxiety and a great number of studies describe an association
      of physical activity and general well-being, mood and anxiety. In line,
      intervention studies describe an anxiolytic and antidepressive activity of
      exercise in healthy subjects and patients. However, the majority of published
      studies have substantial methodological shortcomings. The aim of this paper is to
      critically review the currently available literature with respect to (1) the
      association of physical activity, exercise and the prevalence and incidence of
      depression and anxiety disorders and (2) the potential therapeutic activity of
      exercise training in patients with depression or anxiety disorders. Although the
      association of physical activity and the prevalence of mental disorders,
      including depression and anxiety disorders have been repeatedly described, only
      few studies examined the association of physical activity and mental disorders
      prospectively. Reduced incidence rates of depression and (some) anxiety disorders
      in exercising subjects raise the question whether exercise may be used in the
      prevention of some mental disorders. Besides case series and small uncontrolled
      studies, recent well controlled studies suggest that exercise training may be
      clinically effective, at least in major depression and panic disorder. Although,
      the evidence for positive effects of exercise and exercise training on depression
      and anxiety is growing, the clinical use, at least as an adjunct to established
      treatment approaches like psychotherapy or pharmacotherapy, is still at the
      beginning. Further studies on the clinical effects of exercise, interaction with
      standard treatment approaches and details on the optimal type, intensity,
      frequency and duration may further support the clinical administration in
      patients. Furthermore, there is a lack of knowledge on how to best deal with
      depression and anxiety related symptoms which hinder patients to participate and
      benefit from exercise training.

PMID- 18726138
TI  - SNAP-25 genotype influences NAA/Cho in left hippocampus.
AB  - The SNAP-25 gene is an integral part of the vesicle docking and fusion machinery
      that controls neurotransmitter release. Several post mortem studies revealed a
      reduction of SNAP-25 protein in the hippocampus of patients with schizophrenia
      and bipolar disorder (BD). Thirty-eight patients with schizophrenia, BD or
      obsessive-compulsive disorder and 17 healthy controls participated in the study.
      Proton magnetic resonance spectroscopy in left hippocampus was performed in each
      individual. Three single nucleotide polymorphisms (SNP) of the SNAP-25 gene were
      genotyped. Individuals with the homozygous CC genotype of the DdeI SNP presented
      a significantly higher ratio of N-acetyl-aspartate (NAA)/choline-containing
      compounds (Cho) in the left hippocampus compared to the group of individuals with
      the homozygous TT genotype. The SNAP-25 genotype may modulate synaptic plasticity
      and neurogenesis in the left hippocampus, and altered NAA/Cho ratio may be an
      indicator for this genetic modulation of neuronal function in the hippocampus.

PMID- 18726139
TI  - Continuous versus pulsatile administration of rotigotine in 6-OHDA-lesioned rats:
      contralateral rotations and abnormal involuntary movements.
AB  - Sustained drug delivery providing continuous dopaminergic stimulation is thought
      to prevent or delay the induction of motor complications (dyskinesia) in
      Parkinson's disease, whereas pulsatile administration is supposed to promote
      them. This study investigated the inducibility of sensitization and abnormal
      involuntary movements (AIMs), comparing continuous and pulsatile administration
      of rotigotine with pulsatile administration of 3,4-dihydroxy-L-phenylalanine (L
      DOPA) for reference. Rats were unilaterally lesioned with 6 hydroxydopamine (6
      OHDA). For pulsatile administration, L-DOPA-methylester (10 mg/kg L-DOPA i.p.) or
      rotigotine (1 mg/kg i.p.) were administered once or twice daily. For continuous
      administration, a slow release formulation of rotigotine was injected s.c. at a
      dose of 1 mg/kg every 48 h (experiment I) or every 24 h (experiment II).
      Pulsatile administration of rotigotine and L-DOPA caused contraversive rotations
      increasing progressively upon each successive treatment. AIMs started to occur
      after the second administration of L-DOPA but hardly after pulsatile rotigotine.
      Continuous rotigotine increased rotations, which reached a plateau after the
      second administration. No AIMs were observed under continuous administration. The
      continuous administration of rotigotine did not induce sensitization or AIMs,
      suggesting that continuous stimulation of dopaminergic receptors by rotigotine
      has no propensity to induce dyskinesia in this experimental model.

PMID- 18726140
TI  - Prediction of protein structural classes by Chou's pseudo amino acid composition:
      approached using continuous wavelet transform and principal component analysis.
AB  - A prior knowledge of protein structural classes can provide useful information
      about its overall structure, so it is very important for quick and accurate
      determination of protein structural class with computation method in protein
      science. One of the key for computation method is accurate protein sample
      representation. Here, based on the concept of Chou's pseudo-amino acid
      composition (AAC, Chou, Proteins: structure, function, and genetics, 43:246-255,
      2001), a novel method of feature extraction that combined continuous wavelet
      transform (CWT) with principal component analysis (PCA) was introduced for the
      prediction of protein structural classes. Firstly, the digital signal was
      obtained by mapping each amino acid according to various physicochemical
      properties. Secondly, CWT was utilized to extract new feature vector based on
      wavelet power spectrum (WPS), which contains more abundant information of
      sequence order in frequency domain and time domain, and PCA was then used to
      reorganize the feature vector to decrease information redundancy and
      computational complexity. Finally, a pseudo-amino acid composition feature vector
      was further formed to represent primary sequence by coupling AAC vector with a
      set of new feature vector of WPS in an orthogonal space by PCA. As a showcase,
      the rigorous jackknife cross-validation test was performed on the working
      datasets. The results indicated that prediction quality has been improved, and
      the current approach of protein representation may serve as a useful
      complementary vehicle in classifying other attributes of proteins, such as enzyme
      family class, subcellular localization, membrane protein types and protein
      secondary structure, etc.

PMID- 18726141
TI  - Glutamate is the chemotaxis-inducing factor in placental extracts.
AB  - Human placental extracts are known to help wound healing. Rapid migration of
      neutrophils to the wound site is a prerequisite to the wound healing process. Gel
      filtration analysis of heat-treated placental extract gave the initial cue to the
      small nature of the migration promoting factor of the extract. HPLC analysis of
      the extract revealed glutamate to be the predominant free amino acid. Our studies
      show that glutamate at an optimum concentration of 8 microM induced phenotypic
      neutrophil chemotaxis, as seen in the time lapse and transwell assays. Glutamate
      was also found to induce chemokinesis of the neutrophil, though the stimulation
      of chemotaxis was more pronounced. The glutamate induced chemotaxis was
      accompanied by polarization of the actin cytoskeleton, and by polymerization of F
      actin. These data indicate that glutamate has a strong chemotactic functionality
      in the neutrophil, which could be of interest both therapeutically and in further
      investigation of the molecular basis of chemotaxis.

PMID- 18726142
TI  - A psychosocial risk assessment model (PRAM) for use with pregnant and postpartum
      women in primary care settings.
AB  - Recognition of high rates of mental health morbidity and mortality that affect
      women during the perinatal period has prompted the development of psychosocial
      risk assessment programs. Designed to identify women, at risk, during routine
      health checks and delivered by primary care health service providers, these fit
      within a primary prevention and early intervention strategic approach to the
      reduction of perinatal mental illness and reflect an integrated approach to
      perinatal health services delivery. This paper describes the development and use
      of the psychosocial risk assessment model (PRAM) at the Royal Hospital for Women
      in Sydney, Australia. Data is presented on 2,142 women who attended the Antenatal
      Midwives Clinic between 2002 and 2005. The PRAM guides primary care staff to
      quickly identify women experiencing emotional distress and/or psychosocial
      problems during pregnancy or postnatal checks. Measures used in pregnancy are the
      symptom-based Edinburgh Depression Scale and the psychosocial risk-based
      Antenatal Risk Questionnaire. In postnatal setting the Postnatal Risk
      Questionnaire is used. Scores can be used to compute a Psychosocial Risk Index
      (PRI) to guide individualized care planning, define needs for referral and
      classify groups for clinical and research purposes. Based on the PRI, among 2,142
      women assessed in pregnancy 70.6% were classified as low/no risk (no
      interventions indicated currently), 24.1% as medium risk (in need of monitoring),
      and 5.3% as high risk (complex). The PRAM offers a conceptual framework, methods
      and measures for brief psychosocial assessment with clinical and research
      applications. Postpartum follow up studies of women assessed during pregnancy
      have commenced. Randomized controlled trials and cross-cultural studies are now
      indicated to strengthen the evidence base for the model.

PMID- 18726143
TI  - Influence of oxytocin or epidural analgesia on personality profile in
      breastfeeding women: a comparative study.
AB  - Women undergo physiological and psychological changes during pregnancy, labor and
      lactation. The psychological adaptations can be affective, cognitive and
      behavioral and can be measured by dimensional personality instruments. This study
      aims to compare (1) the personality profile in mothers after birth with a
      normative group of non-lactating women and to examine (2) whether the personality
      profile differs 2 days, 2 months and 6 months after birth between mothers who
      have been exposed to epidural anesthesia, oxytocin administration or neither.
      Sixty-nine primiparae were assigned to four groups: mothers having received
      oxytocin infusion during labor (OT iv group, n = 9), mothers having received
      epidural analgesia with/without oxytocin infusion (EDA group, n = 23), mothers
      having received 10 iU oxytocin intramuscularly after birth (OT im group, n = 15)
      and mothers having received none of these treatments (unmedicated group, n = 22).
      At 2 days and 2 and 6 months postpartum mothers completed the Karolinska Scales
      of Personality (KSP). The unmedicated, the OT iv- and OT im groups scored
      significantly lower on anxiety and aggression related scales and higher on the
      socialization subscale during the entire observation period when compared with a
      normative group. These differences were not observed in the EDA group 2 days
      postpartum. At 2 and 6 months postpartum, the scores of the EDA group had changed
      significantly and were almost similar to the KSP scores of the other groups.
      ANCOVA analysis revealed that OT infusion, over and above the effects of EDA, was
      associated with decreased levels of several anxiety and aggression subscales. We
      conclude that women who received exogenous oxytocin during labor show similar
      positive personality traits during breastfeeding such as reduction in anxiety and
      aggression and increasing socialization, including maternal behavior, that have
      previously been ascribed to endogenous oxytocin. More importantly, these effects
      were not seen at 2 days postpartum in women who received epidural anesthesia
      during labor.

PMID- 18726144
TI  - Immunotherapy of type 1 diabetes.
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which the insulin-producing
      beta cells are destroyed. Diabetic patients manage their hyperglycemia by daily
      insulin injections. However, insulin therapy is by no means a cure. Accordingly,
      a significant effort has been ongoing to develop immunotherapies that effectively
      prevent and/or treat T1D in the clinic. This review focuses on antigen- and
      antibody-based immunotherapies and discusses the respective strengths and
      weaknesses of these approaches.

PMID- 18726145
TI  - Abnormalities in the handling of intracellular bacteria in Crohn's disease: a
      link between infectious etiology and host genetic susceptibility.
AB  - The etiology of Crohn's disease (CD) is still poorly understood, but recent
      advances have highlighted the importance of the innate immune system and the
      critical relationship between the gut flora and the intestinal mucosa. Several
      combinations of genetic factors predisposing to CD have been described, with the
      most significant replicable associations including genes for intracellular
      receptors of bacterial cell walls (NOD2/CARD15) and for bacterial clearance and
      antigen processing via autophagy (ATG16L1 and IRGM). One theoretical link between
      susceptibility genes NOD2/CARD15, ATG16L1, and IRGM is that CD is primarily
      induced by the presence of a dysfunctional immunological response to persistent
      infection by intracellular bacterial pathogens such as Mycobacterium avium
      subspecies paratuberculosis or adherent-invasive Escherichia coli, both first
      rank candidates on the basis of host genetic susceptibility, which concerns
      impaired functions in the defense against intracellular bacteria.

PMID- 18726146
TI  - Host immune response in B-cell lymphomas: friend or foe?
AB  - The interaction of B-cell malignancies with the host immune system is a dynamic
      and bilateral process. Certain lymphomas more commonly arise within a background
      of autoimmunity or chronic infection. Initiation of these tumors is commonly
      reliant on antigenic stimulation and/or T-cell help. Apart from its tumor-fueling
      role, the host immune response plays a critical role in cancer immunosurveillance
      and immunoediting. The concept of immunoediting holds that the immune system
      sculpts the tumor's immunogenicity in a dynamic process that involves three
      essential phases: elimination, equilibrium, and escape. Data obtained by studying
      gene-targeted animals and human lymphomas that support the critical role of the
      immune response in the initiation, progression, and immunoediting of lymphoid
      malignancies are summarized here. A thorough understanding of this interaction
      will lead to the identification of more rational treatment targets and improved
      immunotherapies in B-cell lymphomas.

PMID- 18726147
TI  - Role of the Wnt/beta-catenin network in regulating hematopoiesis.
AB  - The Wnt/beta-catenin pathway plays a significant role in several aspects of cell
      biology, including the stimulation of gene expression, growth, and mobility. Wnt
      proteins activate at least three cascades: Wnt/beta-catenin, Wnt/Ca(2+), and
      planar cell polarity. beta-Catenin is not only a very important element of many
      intracellular signaling pathways, including the Wnt pathway, but it also takes
      part in creating intercellular adhesive junctions. When overexpressed or mutated
      it functions as an oncogen. The Wnt/beta-catenin signaling pathway has been shown
      to play an important role in controlling the proliferation, survival, and
      differentiation of hematopoietic cells. Thus any aberrant signaling through this
      pathway may have a negative influence on hematopoiesis. Indeed, some recent
      findings suggest that Wnt/beta-catenin signaling is dysregulated in leukemias and
      lymphomas. All these data position the Wnt/beta-catenin signaling network as a
      critically important regulator of hematopoiesis and justify future efforts to
      better understand its role in the process of physiological and pathological
      hematopoiesis. The present review summarizes recent advances in this field.

PMID- 18726148
TI  - Ras pathway activation in gliomas: a strategic target for intranasal
      administration of perillyl alcohol.
AB  - INTRODUCTION: Targeted therapy directed at specific molecular alterations is
      already creating a shift in the treatment of cancer patients. Malignant gliomas
      commonly overexpress the oncogenes EGFR and PDGFR and contain mutations and
      deletions of the tumor suppressor genes PTEN and TP53. Some of these alterations
      lead to activation of the P13K/Akt and Ras/MAPK pathways, which provide targets
      for therapy. Perillyl alcohol (POH), the isoprenoid of greatest clinical
      interest, was initially considered to inhibit farnesyl protein transferase.
      Follow-up studies revealed that POH suppresses the synthesis of small G proteins,
      including Ras. Intranasal delivery allows drugs that do not cross the blood-brain
      barrier to enter the central nervous system. Moreover, it eliminates the need for
      systemic delivery, thereby reducing unwanted systemic side effects. MATERIALS AND
      METHODS: Applying this method, a phase I/II clinical trial of POH was performed
      in patients with relapsed malignant gliomas after standard treatment: surgery,
      radiotherapy, and chemotherapy. POH was administrated in a concentration of 0.3%
      volume/volume (55 mg) four times daily in an interrupted administration schedule.
      The objective was to evaluate toxicity and progression-free survival (PFS) after
      six months of treatment. The cohort consisted of 37 patients, including 29 with
      glioblastoma multiforme (GBM), 5 with grade III astrocytoma (AA), and 3 with
      anaplastic oligodendroglioma (AO). Neurological examination and suitable image
      analysis (computed tomography (CT), magnetic resonance imaging (MRI)) established
      disease progression. Complete response was defined as neurological stability or
      improvement of conditions, disappearance of CT/MRI tumor image, and
      corticosteroid withdraw; partial response (PR) as > or =50 reduction of CT/MRI
      tumor image, neurological stability, or improvement of conditions and
      corticosteroid requirement; progressive course (PC) as > or =25 increase in
      CT/MRI tumor image or the appearance of a new lesion; and stable disease as a
      lack of any changes in the CT/MR tumor image or neurological status. RESULTS:
      After six months of treatment, PR was observed in 3.4% (n=1) of the patients with
      GBM and 33.3% (n=1) with AO; stable disease in 44.8% (n=13) with GBM, 60% (n=3)
      with AA, and 33.3% (n=1) with AO; and PC in 51.7% (n=15) with GBM, 40% (n=2),
      with AA and 33.3% (n=1) AO. PFS (sum of PRs and stable disease) was 48.2% for
      GBM, 60% for AA, and 66.6% for AO patients. CONCLUSIONS: The preliminary results
      indicate that intranasal administration of the signal transduction inhibitor POH
      is a safe, noninvasive, and low-cost method. There were no toxicity events and
      the regression of tumor size in some patients is suggestive of antitumor
      activity.

PMID- 18726149
TI  - Relationship between impaired apoptosis of lymphocytes and distribution of
      dendritic cells in peripheral blood and synovial fluid of children with juvenile
      idiopathic arthritis.
AB  - INTRODUCTION: The pathogenesis of juvenile idiopathic arthritis (JIA) is not
      fully understood. Recently the present authors described disturbed apoptosis of
      JIA lymphocytes in both peripheral blood (PB) and synovial fluid (SF) as well as
      an abnormal distribution of blood dendritic cells (BDCs) between the PB and SF in
      this disease. Possible relationships between these events during the development
      of JIA process are assessed here. MATERIALS AND METHODS: Lymphocyte apoptosis and
      BDC counts were assessed in the PB and SF of untreated JIA children. Lymphocyte
      apoptosis was analyzed by the Annexin-V/propydium iodide assay. Total DC (TDC)
      number was based on the sum of three BDC subpopulations determined using a panel
      of monoclonal antibodies against BDC antigens (BDCA): myeloid type 1 (mDC1, BDCA
      1(+)/HLA-DR(+)/CD19(-)), myeloid type 2 (mDC2, BDCA-3(+)/HLA-DR(+)/CD14(-)), and
      plasmacytoid (pDC, BDCA-2(+)/HLA-DR(+)/CD123(+)). Cells were enumerated by the
      flow cytometric "single-platform" method. The concentration of tumor necrosis
      factor (TNF)-alpha and the distribution of particular lymphocyte subtypes in both
      PB and SF were also investigated. RESULTS: There was significant positive
      correlation between apoptosis of PB lymphocytes and SF TDC count (p=0.002) as
      well as SF TNF-alpha concentration (p=0.007). SF TNF-alpha levels also correlated
      with SF TDC count (p=0.003). Moreover, JIA SF was distinctly enriched with CD4+
      and CD8+ T lymphocytes and included CD4(+)/CD25(high) cells as well. There was
      significant positive correlation between the number of CD4(+)/CD25(high) cells
      and SF JIA BDC count (p=0.015). CONCLUSIONS: These data suggest a possible link
      between impaired apoptosis of PB/SF lymphocytes and increased recruitment of PB
      BDCs to SF and other elements of the immune system in JIA, including regulatory
      CD4+/CD25high cells.

PMID- 18726150
TI  - Faux pas detection and intentional action in Asperger Syndrome. A replication on
      a French sample.
AB  - In the present study, we investigated mind reading abilities in a group of adults
      with Asperger Syndrome (AS) by using the faux pas task, an advanced test of
      theory of mind (Baron-Cohen et al. (1999). Journal of Autism and Developmental
      Disorders, 29, 407-418). The faux pas is a particular case of a non-intentional
      action reflecting an involuntary socially inappropriate behavior. Here,
      individuals with AS over-detected faux pas stories, failed to provide correct
      justifications of the speaker's behavior and were unaware of the mistaken belief
      and of the resulting emotional impact, whereas they appeared to be responsive to
      social rule violations. We hypothesized that because of an impaired theory-of
      mind, individuals with AS may develop compensatory cognitive strategies based on
      overlearned abstract knowledge about normative rules.

PMID- 18726151
TI  - Relationship of race-, sexual orientation-, and HIV-related discrimination with
      adherence to HIV treatment: a pilot study.
AB  - Adherence to highly active antiretroviral therapy (HAART) must be close to
      perfect in order to maintain suppression of HIV viral load, and to prevent the
      development of drug resistant strains of HIV. People living with HIV (PLWH) often
      report low levels of adherence. One variable that has been linked to poor
      adherence is perceived discrimination; however, research has generally not
      considered the possible unique effects of different types of discrimination on
      adherence. The present pilot study aimed to examine the association of three
      types of discrimination (due to HIV+ status, race, or sexual orientation) with
      adherence among 57 PLWH. Logistic regression analyses were conducted to
      demonstrate the relationships between each type of discrimination and self
      reported adherence. Racial discrimination significantly predicted lower adherence
      levels, whereas sexual orientation- and HIV-related discrimination did not.
      Results underscore the importance of addressing discrimination issues,
      specifically racial, when designing interventions to improve adherence to HAART.

PMID- 18726152
TI  - Validation of a questionnaire to assess self-reported colorectal cancer screening
      status using face-to-face administration.
AB  - PURPOSE: The aim of this study was to assess the accuracy of a National Cancer
      Institute (NCI)-developed colorectal cancer screening questionnaire. METHODS: We
      conducted 36 cognitive interviews and made iterative changes to the questionnaire
      to improve comprehension. The revised questionnaire was administered face-to-face
      to 201 participants. The primary outcome was agreement between questionnaire
      responses and medical records for whether or not a participant was up-to-date for
      any colorectal cancer screening test. RESULTS: Comprehension of descriptions and
      questions was generally good; however, the barium enema description required
      several revisions. The sensitivity of the questionnaire for up-to-date screening
      status was 94%, specificity 63%, and concordance 88%. CONCLUSIONS: The modified
      questionnaire was highly sensitive for determining if a person was up-to-date for
      any colorectal cancer screening test, although the specificity was low. Given the
      difficulty of obtaining all relevant records, self-report using this
      questionnaire is a reasonable option for identifying people who have undergone
      testing.

PMID- 18726153
TI  - Lansoprazole for long-term maintenance therapy of erosive esophagitis: double
      blind comparison with ranitidine.
AB  - In a study evaluating the efficacy and safety of lansoprazole to prevent the
      relapse of erosive esophagitis (EE), 206 of 241 patients (85%) healed after open
      label treatment with lansoprazole 30 mg once daily for 8 weeks and received
      double-blind maintenance treatment with lansoprazole 15 mg once daily or
      ranitidine 150 mg twice daily for up to 1 year. At 1 year, 67% of lansoprazole
      treated and 13% of ranitidine-treated patients remained healed (P<0.001).
      Lansoprazole-treated patients experienced significantly greater symptom relief
      (P<0.001), and, if asymptomatic at entry into the maintenance phase, remained
      asymptomatic for significantly longer than ranitidine-treated patients (P<0.001).
      Symptom status correlated with healing (P=0.001), supporting the symptom-directed
      management of EE. Both treatments were well tolerated and no unexpected events
      occurred. Daily therapy with lansoprazole to prevent the relapse of EE is
      effective, well tolerated, and superior to ranitidine in the maintenance of
      healing and symptom relief.

PMID- 18726154
TI  - Synbiotics decrease the incidence of septic complications in patients with severe
      SIRS: a preliminary report.
AB  - The purpose of this study was to evaluate if synbiotic therapy can correct the
      deteriorated gut flora and environment in patients with severe systemic
      inflammatory response syndrome (SIRS). Twenty-nine SIRS patients, who fulfilled a
      serum C-reactive protein (CRP) level >10 mg/dl, received synbiotics
      (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides) (S
      group) and were compared with previous observations in 26 patients without
      synbiotics (NS group). Analysis of fecal flora confirmed that patients in the S
      group had significantly greater levels of beneficial Bifidobacterium,
      Lactobacillus, and total organic acids (particularly short-chain fatty acids)
      than those in the NS group. The incidence of infectious complications such as
      enteritis, pneumonia, and bacteremia was significantly lower in the S group than
      in the NS group. Synbiotics maintain the gut flora and environment and decrease
      the incidence of septic complications in patients with severe SIRS. Further
      randomized controlled study is necessary to determine the effects of synbiotics.

PMID- 18726155
TI  - Treatment models for treating patients with combined mental illness and
      developmental disability.
AB  - The presence of co-occurring psychiatric disorders among individuals with
      developmental disability (DD) requires clinicians to adjust and modify standard
      mental health assessment and treatment planning. In particular, assessment
      includes input from a multi-disciplinary team and as a result, diagnosis is
      frequently a synthesis of data from many different points of view. Treatment
      planning and implementation commonly include a collection of highly specialized,
      individualized programs that focus on the long term management of both disorders.
      Crises and recurrence of mental disorders are commonplace in part due to the
      presence of ongoing risk and vulnerability factors for mental disorders. As a
      result, the need for emergency interventions, specialized respite services,
      hospitalization and other transition services is extensive. The quality,
      availability and access to these services vary considerably. Many programs are
      concentrated in metropolitan or university-based centers and pose hardships based
      on geographic distance. The availability and utilization of services is affected
      by political, economic, socio-cultural and psychological forces that impact both
      the willingness to use services and the distribution of professionals trained and
      qualified to manage individuals with dual diagnoses. The complex interaction
      between each of these factors determines the structure, function, and capacity
      for innovation built into current service models.

PMID- 18726156
TI  - Anxiety disorders in persons with developmental disabilities: empirically
      informed diagnosis and treatment. Reviews literature on anxiety disorders in DD
      population with practical take-home messages for the clinician.
AB  - Anxiety disorders are common in individuals with developmental disabilities
      (DDs), although they may not be diagnosed and treated as often as they are in
      patients without DDs. Patients with mental retardation, autism, and other
      pervasive developmental disorders may exhibit comorbid anxiety disorders, such as
      generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), phobias,
      and other anxiety symptoms at much higher rates than in the general population,
      but identification of these comorbid anxiety disorders may be made more difficult
      by the presence of the DD and concurrent difficulties with communication, other
      behavior problems, the lack of standardized assessments specific to diagnosing
      patients with DDs and psychiatric comorbidities, and the need for greater
      collateral sources of assessment information. In addition, systematic study of
      the treatment of anxiety in patients with DD is limited to a relatively small
      number of empirical studies done specifically in these patients along with case
      reports and theoretical reviews on the extension and modification of more well
      studied treatments used for anxiety in patients without DDs. The present article
      reviews the literature on the prevalence, features, assessment and diagnosis of
      anxiety disorders in individuals with DDs, and also reviews empirical studies of
      pharmacological and psychological treatment of patients with comorbid anxiety and
      DD and summarizes the findings. Recommendations are made to guide treatment and
      further research in this area.

PMID- 18726157
TI  - Diagnosis and treatment of aggression in individuals with developmental
      disabilities.
AB  - Aggressive behavior is a common referral problem for individuals with
      developmental disabilities (DD), placing them at risk for institutionalization,
      social isolation, physical restraint, over-use of medication to treat behavior
      problems, exclusion from services, and becoming a victim of abuse. Aggression
      strains relationships between individuals being supported and their caregivers,
      whether professionals or family members. The treatment of aggression is persons
      with DD, with or without comorbid mental illness, remains a controversial area
      and changes in practice have been slow to come. The evidence related to
      pharmacotherapy and psychological treatment is, in general, either lacking or
      poor. This does not suggest that these treatments are necessarily ineffective but
      that there is not enough good quality evidence to support their usefulness. This
      review considers the prevalence and correlates of aggression, as well as possible
      causative factors. The relationship between mental illness, intellectual
      disability and aggression is explored. The psychopharmacological and
      psychological treatment literature is reviewed with implications for clinical
      care and future research.

PMID- 18726158
TI  - Diagnosis and treatment of mood disorders in adults with developmental
      disabilities.
AB  - While the idea that individuals with developmental disabilities (DD) can suffer
      from mental illness has been largely accepted since the late 1980's, this is
      still an underserved and poorly studied population. In particular, mood disorders
      have traditionally been misdiagnosed, under-recognized and poorly treated.
      Through the years, reported rates of mood disorders in adults with DD have varied
      widely. Recent epidemiological studies have focused on community samples and find
      rates of mood disorders from 3 to 8.1%. Mood disorders are found to be more
      prevalent than psychotic disorders or anxiety disorders. The empirical literature
      on assessment of mood symptoms in adults with DD is limited, particularly in
      individuals with severe and profound DD. Several tools have been developed to
      assist in identification and diagnosis. However, the work on their psychometric
      properties and validity studies is still quite limited. The treatment literature
      is sparse and focused primarily on pharmacotherapy. This review considers the
      epidemiology and diagnosis of mood disorders in individuals with DD. Recent
      developments in assessment are reviewed. The literature regarding pharmacological
      treatment with antidepressants, mood stabilizers, electroconvulsive therapy and
      antipsychotics is summarized and the current state of psychological treatments
      for mood disorders in persons with DD is presented. Implications for clinical
      care and future research are considered.

PMID- 18726159
TI  - A review of empirical evidence of somatic treatment options for the MI/DD
      population.
AB  - This article reviews recent evidence in the literature for the use of
      psychotropic and other somatic treatments in the management of patients with
      mental retardation (MR). The search methodology included peer-reviewed English
      language publications in PubMed and PsychINFO with the words Mental Retardation,
      Intellectual Disability, Developmental Disability and Mental Disorders/Drug
      Therapy or Antipsychotic medications, Psychiatric Somatic therapies, Neuroleptic
      Drugs, Antidepressants and Electroconvulsive Therapy from 1998 to 2008. The
      review revealed few randomized controlled trials on the medications frequently
      prescribed for patients with MR. Three RCTs of Risperidone in children, one
      combining adults and children and one with adults only are discussed. There was
      one RCT involving Quetiapine and one on Citalopram. There is little evidence to
      support the scope of psychotropic medication use in the MR population though the
      field is advancing. The contribution of psychiatric illness to challenging
      behaviors is not systematically addressed in the literature.

PMID- 18726160
TI  - Ingestion of black chokeberry fruit extract leads to intestinal and systemic
      changes in a rat model of prediabetes and hyperlipidemia.
AB  - This report presents a complex analysis of changes proceeding in the gut, blood
      and internal organs of rats with induced oxidative stress, glucose intolerance
      and hyperlipidemia after dietary supplementation with an extract from black
      chokeberry (Aronia melanocarpa) fruit, that is a condensed source of polyphenols
      (714 mg/g), especially anthocyanin glycosides (56.6%). The disturbances mimicking
      those observed in metabolic syndrome were induced by a high-fructose diet and
      simultaneous single injection of streptozotocin (20 mg/kg). Dietary
      supplementation with the chokeberry fruit extract (0.2%) decreased activity of
      maltase and sucrase as well as increased activity of lactase in the mucosa of the
      small intestine. Its ingestion led also to the improvement of antioxidant status,
      especially, the concentration of a lipid peroxidation indicator (TBARS) in organ
      tissues (liver, kidney and lung) was normalized; some cholesterol-lowering and
      distinct hypoglycemic actions were also observed. The mechanism of glucose
      reduction is likely to be multifactorial, and we suggest the factors related with
      the decreased activity of mucosal disaccharidases important for further
      investigation. In conclusion, chokeberry fruit derivatives may act as a promising
      supplementary therapeutic option in the prevention and treatment of disorders
      occurring in metabolic syndrome, as well as their complications.

PMID- 18726161
TI  - New insights into the mechanisms of fibrosis and sclerosis in diabetic
      nephropathy.
AB  - Progression of diabetic nephropathy (DN) is manifested by gradual scarring of
      both the renal glomerulus and tubulointerstitial region. Over the past several
      years, the general understanding of the pathogenic factors that lead to renal
      fibrosis in DN has expanded considerably. In this review, some of the important
      factors that appear to be involved in driving this fibrosing process are
      discussed, with special emphasis on newer findings and insights. It is now clear
      that multiple cell types in the kidney contribute to progressive fibrosis in DN.
      New concepts about bradykinin, TGF-beta and eNOS signaling as well as JAK/STAT
      activation and the central role of inflammation in both glomerular and
      tubulointerstitial fibrosis are discussed.

PMID- 18726163
TI  - Preservation of duplicate genes by originalization.
AB  - Neofunctionalization, subfunctionalization and increasing gene dosage were
      proposed to be the possible ways to explain duplicate-gene preservation in
      previous studies. However, in some natural populations, such as yeast
      Saccharomyces cerevisiae, a considerable proportion of the duplicate genes
      originated from ancient whole genomic duplication (WGD) is preserved till now,
      which cannot be sufficiently explained by these mechanisms. In this article, we
      present another possible way to explain this conundrum-originalization, by which
      duplicate genes are both preserved intact at a high frequency in the population
      under only purifying selection. With approximate equal rates of mutation at the
      two duplicated loci, analytical, numerical and simulation results consistently
      show that the mean time to nonfunctionalization for unlinked haploinsufficient
      gene duplication might become markedly prolonged, which results from
      originalization. These theoretical results imply that originalization might be an
      alternative effective and temporary way of preserving duplicate genes.

PMID- 18726162
TI  - Methodologies for segregation analysis and QTL mapping in plants.
AB  - Most characters of biological interest and economic importance are quantitative
      traits. To uncover the genetic architecture of quantitative traits, two
      approaches have become popular in China. One is the establishment of an
      analytical model for mixed major-gene plus polygenes inheritance and the other
      the discovery of quantitative trait locus (QTL). Here we review our progress
      employing these two approaches. First, we proposed joint segregation analysis of
      multiple generations for mixed major-gene plus polygenes inheritance. Second, we
      extended the multilocus method of Lander and Green (1987), Jiang and Zeng (1997)
      to a more generalized approach. Our methodology handles distorted, dominant and
      missing markers, including the effect of linked segregation distortion loci on
      the estimation of map distance. Finally, we developed several QTL mapping
      methods. In the Bayesian shrinkage estimation (BSE) method, we suggested a method
      to test the significance of QTL effects and studied the effect of the prior
      distribution of the variance of QTL effect on QTL mapping. To reduce running
      time, a penalized maximum likelihood method was adopted. To mine novel genes in
      crop inbred lines generated in the course of normal crop breeding work, three
      methods were introduced. If a well-documented genealogical history of the lines
      is available, two-stage variance component analysis and multi-QTL Haseman-Elston
      regression were suggested; if unavailable, multiple loci in silico mapping was
      proposed.

PMID- 18726164
TI  - Equine placenta expresses glutamine synthetase.
AB  - In most mammalian species the developing fetus utilizes large amounts of
      glutamine derived both from the maternal circulation and synthesized de novo in
      the placenta. The present study was designed to determine the role of the
      placenta in glutamine synthesis in the horse. The placentae from eight
      Standardbred mares were sampled immediately after parturition together with
      additional tissues obtained at necropsy from three Standbred mares during
      diestrous. Glutamine synthetase protein was detectable in the non-pregnant horn
      of the placenta in amounts similar to those seen in gluteus muscle, but the
      amount in the pregnant horn was two times greater than in the non-pregnant horn.
      Glutamine was the second most abundant amino acid in amniotic fluid at a
      concentration of 310 +/- 26 micromole/L with that of glycine being 535 +/- 48
      micromole/L. The most abundant amino acids in placental tissue were glycine
      (3,732 +/- 194 micromole/Kg), glutamate (3,500 +/- 343 micromole/Kg) and
      glutamine (2,836 +/- 208 micromole/Kg). The results illustrate the importance of
      glutamine to the equine fetus and establish that the placenta, particularly the
      pregnant horn, has considerable capacity for glutamine synthesis.

PMID- 18726165
TI  - Prevalence of Toxoplasma gondii and Neospora caninum infections in sheep from
      Federal District, central region of Brazil.
AB  - Serum samples from 1028 sheep were collected from 32 herds within Federal
      District, in the central region of Brazil. The samples were examined by indirect
      fluorescent antibody test (IFAT) using sera diluted 1:64 and 1:50 as cut-off
      values for the detection of antibodies against Toxoplasma gondii and Neospora
      caninum, respectively. The observed prevalence for T. gondii infection was 38.22%
      (26.81%<CI 0.95<49.62%), and the titers ranged from 64 to 65536. The observed
      prevalence for N. caninum infection was 8.81% (7.08%<CI 0.95<10.53%). The titers
      ranged from 50 to 51200. The reactant sera to both pathogens corresponded to
      4.67% of the samples. The risk factors were not determined because of the absence
      of negative herds for T. gondii and the high proportion of positive herds for N.
      caninum (87.50%). The prevalence for T. gondii infection was significantly higher
      among males than in females. The present work is the first report on
      seroprevalence of T. gondii and N. caninum in sheep from Federal District and
      shows that infection by both parasites is widespread in the ovine population from
      this region.

PMID- 18726166
TI  - Proteins and peptidases from conidia and mycelia of Scedosporium apiospermum
      strain HLPB.
AB  - The conidia-mycelia transformation is an essential step during the life cycle of
      the fungal human pathogens of the Pseudallescheria boydii complex. In the present
      study, we have analyzed the protein and peptidase profiles in two distinct
      morphological stages, conidia and mycelia, of Scedosporium apiospermum sensu
      stricto. Proteins synthesized by the mycelia, migrating at the ranges of 62-48
      and 22-18 kDa, were not detected from the conidial extract. Conidia produced a
      single cellular peptidase of 28 kDa able to digest copolymerized albumin, while
      mycelia yielded 6 distinct peptidases ranging from 90 to 28 kDa. All proteolytic
      enzymes were active at acidic pH and fully inhibited by 1,10-phenanthroline,
      characterizing these activities as metallo-type peptidases. Quantitative
      peptidase assay, using soluble albumin, showed a high metallopeptidase production
      in mycelial cells in comparison with conidia. The regulated expression of
      proteins and peptidases in different morphological stages of S. apiospermum
      represents a potential target for isolation of stage-specific markers for
      biochemical and immunological analysis.

PMID- 18726167
TI  - Intussusception in the adult: an unsuspected case of Peutz-Jeghers syndrome with
      review of the literature.
AB  - Peutz-Jeghers syndrome is an uncommon genetic defect in the signal pathways of
      growth. The incidence has most recently been estimated to be in the range of 1
      per 120,000 live births [1]. It is characterized by hamartomas throughout the
      gastrointestinal tract, mucocutaneous melanotic spots and increased
      predisposition to malignancy. The infrequent presentation of this syndrome in
      most practice combined with some less well-known diagnostic features may
      contribute to a misdiagnosis. Further, understanding of the genetic defect
      leading to the phenotypic syndrome and the future implications of this defect
      continue to evolve. Therefore we present a review in the setting of a case of
      misdiagnosed Peutz-Jeghers syndrome to portray illuminating features of the
      syndrome and review the literature.

PMID- 18726168
TI  - Recurring MLH1 deleterious mutations in unrelated Chinese Lynch syndrome families
      in Singapore.
AB  - Lynch syndrome is an autosomal dominant disorder due to mutations in DNA mismatch
      repair genes, causing young onset colorectal cancer and extra-colonic cancers
      such as endometrial and stomach cancers. We genotyped MLH1 and MSH2 in patients
      suspected to have Lynch syndrome and correlated patient clinical characteristics
      and family history with deleterious mutations. Eighty-five unrelated patients
      participated. Comprehensive sequencing was performed for MLH1 and MSH2, including
      all coding regions, splice-site junctions and promoter regions. Of the 29
      different mutations found, 11 were deleterious, of which 10 were in MLH1 and 1 in
      MSH2. Three recurring MLH1 deleterious mutations were found in two unrelated
      Chinese patients each, and haplotype analysis suggested common ancestral origin
      for the recurring mutations and possible founder effect. Families with clinical
      diagnosis of HNPCC (i.e. family history which fulfills the Amsterdam I/II
      criteria) was the strongest predictor for finding a deleterious mutation, and
      stomach cancer was the most commonly reported extra-colonic cancer in families
      found with a deleterious MLH1 or MSH2 mutation. The observation of recurring
      deleterious MLH1 mutations in our study suggests possible founder effect and may
      have implications on genetic testing in Asia.

PMID- 18726169
TI  - Molecular identification and characterization of a gene associated with the onset
      of tapping panel dryness (TPD) syndrome in rubber tree (Hevea brasiliensis
      Muell.) by mRNA differential display.
AB  - In rubber tree (Hevea brasiliensis), tapping panel dryness (TPD) syndrome is
      considered as a complex physiological disorder which affects latex biosynthesis.
      To identify differentially expressed genes between healthy and TPD-affected
      trees, mRNA differential display reverse transcriptase polymerase chain reaction
      (DDRT-PCR) analysis was performed. We isolated 10 differentially expressed cDNA
      fragments of which one cDNA encoding a putative TOM20 like protein was
      identified. The cDNA (1,024 bp), corresponding to the HbTOM20 gene (H evea b
      rasiliensis Translocase of the Outer Mitochondrial Membrane), contained an open
      reading frame to code for 202 amino acid protein with a theoretical pI value of
      9.5 and the calculated protein M (W) was 23.5 kDa. The predicted amino acid
      sequence contained conserved domains of TOM20 like proteins in the N-terminal.
      The protein HbTOM20 has 32% and 27% similarity to Populus TOM20 and Solanum
      TOM20, respectively. Both semi-quantitative RT-PCR and Northern blot results
      revealed that the HbTOM20 expression was significantly down-regulated in TPD
      affected trees compared to healthy one. Accumulation of HbTOM20 mRNA transcripts
      was significantly higher in the bark tissues collected from healthy region than
      that of partially affected by TPD (partially dried) while barely detectable in
      completely TPD-affected area. Differential expression pattern was noticed in
      three rubber clones representing various degrees of TPD tolerance. These results
      suggest that down-regulation of HbTOM20 in TPD-affected trees may play an
      important role in alteration of mitochondrial metabolism resulting in impaired
      latex biosynthesis.

PMID- 18726170
TI  - High prevalence of hepatitis B virus pre-S mutation and its association with
      hepatocellular carcinoma in Qidong, China.
AB  - We investigated the frequency and the clinical relevance of hepatitis B virus
      (HBV) pre-S mutations in Qidong, China. The results showed HBV pre-S mutants were
      detected in 48.4% (47/97) of patients with HBV infection. Both pre-S deletion and
      pre-S2 start codon mutations were more frequently found in HCC than in CH
      patients (51.1% vs. 18.0%, P < 0.01 and 21.2% vs. 8.0%, P = 0.06). In most cases,
      pre-S mutants coexisted with the wild-type HBV strain. Longitudinal observation
      clearly revealed that in four of five cases, HBV deletion mutants emerged during
      the course of HBV infection and eventually became the predominant or exclusive
      viral population at the stage of HCC. Thus, it was concluded that HBV pre-S
      mutations were highly prevalent and closely related to HCC in Qidong. Our results
      also provided direct evidence that pre-S deletion mutants were not acquired from
      the beginning of infection but arose de novo during the progression of liver
      disease.

PMID- 18726171
TI  - Six novel begomoviruses infecting tomato and associated weeds in Southeastern
      Brazil.
AB  - The incidence of tomato-infecting begomoviruses has sharply increased in Brazil
      following the introduction of the B biotype of the whitefly vector in the early
      1990s. Five definitive species and six tentative species have been described
      since then. Here, we report the detection of members of an additional six novel
      species, three in tomato and three infecting weeds that are commonly associated
      with tomato fields: Blainvillea rhomboidea, Sida rhombifolia and Sida micrantha.
      Tomato and weed samples were collected in two major tomato-growing regions of
      southeastern Brazil in 2005 and 2007. Two of the novel viruses were present in
      tomato plants collected in Paty do Alferes, Rio de Janeiro state. Three novel
      viruses were present in weed samples collected in Coimbra, Minas Gerais state.
      One virus was present in tomato samples collected at both locations. Genome
      features indicate that all six species are typical New World, bipartite
      begomoviruses. However, the viruses belonging to two of the novel species did not
      cluster with the Brazilian viruses in a phylogenetic tree. These species could
      represent a distinct lineage of New World begomoviruses, found in Brazil for the
      first time.

PMID- 18726172
TI  - Side-chain oxidative damage to cysteine on a glassy carbon electrode.
AB  - In this paper, oxidative damage to the cysteine (CySH) side-chain on a glassy
      carbon electrode (GCE) was investigated. Voltammetric studies show that there are
      three anodic peaks for the oxidation of CySH, which arise from (1) the oxidation
      of the -SH side-chain, forming cystine (0.71 V, vs. SCE) and (2) CySO( x )H, x =
      2, 3 (0.98 V vs. SCE), and (3) the oxidation of the amino acid carboxyl group
      (around 1.51 V vs. SCE). The influence of dissolved oxygen, pH, scan rate, scan
      time, temperature and CySH concentration were investigated and the oxidative
      mechanism proposed. The peaks near 0.71 and 0.98 V are the promising candidates
      for measuring the oxidation of CySH on the GCE. This paper provides a new
      strategy for researching oxidative damage of amino acids, sulfur-containing
      peptides and proteins.

PMID- 18726173
TI  - The bacterial LexA transcriptional repressor.
AB  - Bacteria respond to DNA damage by mounting a coordinated cellular response,
      governed by the RecA and LexA proteins. In Escherichia coli, RecA stimulates
      cleavage of the LexA repressor, inducing more than 40 genes that comprise the SOS
      global regulatory network. The SOS response is widespread among bacteria and
      exhibits considerable variation in its composition and regulation. In some well
      characterised pathogens, induction of the SOS response modulates the evolution
      and dissemination of drug resistance, as well as synthesis, secretion and
      dissemination of the virulence. In this review, we discuss the structure of LexA
      protein, particularly with respect to distinct conformations that enable
      repression of SOS genes via specific DNA binding or repressor cleavage during the
      response to DNA damage. These may provide new starting points in the battle
      against the emergence of bacterial pathogens and the spread of drug resistance
      among them.

PMID- 18726174
TI  - Take the 'A' train: on fast tracks to the cell surface.
AB  - Cholesterol, certain lipids, membrane-bound and soluble proteins, as well as
      viruses that are synthesized in the endoplasmic reticulum (ER), reach the plasma
      membrane (PM) via non-classical pathway(s) that remain poorly understood. Typical
      for this transport is (i) its insensitivity to brefeldin A (BFA), which
      dissociates selected coat complexes from membranes, resulting in the disassembly
      of the Golgi apparatus; (ii) its rapid kinetics as compared to the classical
      secretory pathway; and (iii) its role in the trafficking of lipid raft
      components. Based on results showing that the intermediate compartment (IC) at
      the ER-Golgi boundary constitutes a stable tubular network that maintains its
      dynamics in the presence of BFA, we propose that two bidirectional Golgi-bypass
      pathways to the PM exist, a direct route from early IC elements, and another,
      reminiscent of the yeast secretory pathway, from late IC elements via the
      endosomal system. These pathways have implications for the organization of the
      secretory processes in different cell types.

PMID- 18726175
TI  - Endosome protein sorting: motifs and machinery.
AB  - The steady-state localisation of membrane proteins in the endocytic system is the
      result of many sorting events that occur at various points throughout the
      endosomal pathway. A protein that has been endocytosed from the plasma membrane
      or sorted at the trans-Golgi network (TGN) and transported to an endosome will
      ultimately be delivered to one of three destinations: the plasma membrane, the
      TGN or the lysosome. Where a membrane protein is trafficked to depends on the
      interactions between sorting motifs present in the membrane protein and the
      machinery that can decode these motifs. Much of the protein machinery that
      recognises sorting motifs is conserved from yeast to man, and in this review I
      will discuss this machinery and the motifs that govern endosomal protein sorting.

PMID- 18726176
TI  - Phosphoinositides as regulators of membrane trafficking in health and disease.
AB  - Membrane trafficking is crucial in the homeostasis of the highly
      compartmentalized eukaryotic cells. This compartmentalization occurs both at the
      organelle level, with distinct organelles maintaining their identities while also
      intensely interchanging components, and at a sub-organelle level, with adjacent
      subdomains of the same organelle containing different sets of lipids and
      proteins. A central question in the field is thus how this compartmentalization
      is established and maintained despite the intense exchange of components and even
      physical continuities within the same organelle. The phosphorylated derivatives
      of phosphatidylinositol, known as the phosphoinositides, have emerged as key
      components in this context, both as regulators of membrane trafficking and as
      finely tuned spatial and temporal landmarks for organelle and sub-organelle
      domains. The central role of the phosphoinositides in cell homeostasis is
      highlighted by the severe consequences of the derangement of their metabolism
      caused by genetic deficiencies of the enzymes involved, and from the systematic
      hijacking of phosphoinositide metabolism that pathogens operate to promote their
      entry and/or survival in host cells.

PMID- 18726177
TI  - Membrane fusion: SNAREs and regulation.
AB  - SNARE (SNAP receptor) proteins drive intracellular membrane fusion and contribute
      specificity to membrane trafficking. The formation of SNAREpins between membranes
      is spatially and temporally controlled by a network of sequentially acting
      accessory components. These regulators add an additional layer of specificity,
      arrest SNAREpin intermediates, lower the energy required for fusion, and couple
      membrane fusion to triggering signals. The functional activity of some of these
      regulators determines the plasticity of regulated exocytosis.

PMID- 18726178
TI  - Regulation of secretory vesicle traffic by Rab small GTPases.
AB  - Secretion is a fundamental biological activity of all eukaryotic cells by which
      they release certain substances in the extracellular space. It is considered a
      specialized mode of membrane trafficking that is achieved by docking and fusion
      of secretory vesicles to the plasma membrane (i.e., exocytosis). Secretory
      vesicle traffic is thought to be regulated by a family of Rab small GTPases,
      which are regulators of membrane traffic that are common to all eukaryotic cells.
      Classically, mammalian Rab3 subfamily members were thought to be critical
      regulators of secretory vesicle exocytosis in neurons and endocrine cells, but
      recent genetic and proteomic studies indicate that Rab3 is not the sole Rab
      isoform that regulates secretory vesicle traffic. Rather, additional Rab
      isoforms, especially Rab27 subfamily members, are required for this process. In
      this article I review the current literature on the function of Rab isoforms and
      their effectors in regulated secretory vesicle traffic.

PMID- 18726179
TI  - Myosins in the secretory pathway: tethers or transporters?
AB  - It is generally thought that microtubule-associated motors insure long-range
      movements of the secretory vesicles from the center of the cell to its periphery,
      while myosins insure short-range movements at the cell periphery. However,
      several of the myosins that have been reported during the last decade to be
      involved in the exocytic pathway are not processive, meaning that they do not
      have the ability to move cargos along actin polymers. We will review here the
      possible mechanisms by which these myosins could contribute to the traffic of
      secretory proteins from the Golgi complex to the plasma membrane.

PMID- 18726180
TI  - The life cycle of a transport vesicle.
AB  - Vesicular transport is the basic communication mechanism between different
      compartments in a cell and with the environment. In this review I discuss the
      principles of vesicle generation and consumption with particular emphasis on the
      different types of coat proteins and the timing of the shedding of the coat
      proteins from transport containers. In recent years it has become clear that
      there are more coat complexes than the classical COPI, COPII and clathrin coats.
      These additional coats may generate vesicles that transport cargo in a temporally
      and/or spatially controlled manner. Work over the last years suggests that GTP
      hydrolysis occurs early during vesicle biogenesis, destabilizing the coat perhaps
      before fission of the vesicle from the donor membrane occurs. Recent findings
      imply, however, that tethers at the receiving compartment specifically detect the
      coat on vesicle.

PMID- 18726181
TI  - Membrane traffic in the secretory pathway.
AB  - During the last 20 years remarkable achievements have been made in the
      understanding of the molecular basis of membrane traffic in the secretory
      pathway. A combination of morphological, biochemical and genetical approaches
      revealed the identity of various compartments and transport intermediates, and
      provided basic functional insights into membrane trafficking. Recently, live cell
      imaging approaches further refined our understanding of the underlying mechanisms
      of budding, transport and fusion of transport containers, led to the discovery of
      new pathways and triggered new concepts as to how membrane traffic is
      orchestrated. This multi-author review highlights recent advances in membrane
      traffic by focusing on transport vesicles as the central mediators of
      communication in the secretory pathway.

PMID- 18726183
TI  - Proliferating cell nuclear antigen: a proteomics view.
AB  - Proliferating cell nuclear antigen (PCNA), a cell cycle marker protein, is well
      known as a DNA sliding clamp for DNA polymerase delta and as an essential
      component for eukaryotic chromosomal DNA replication and repair. Due to its
      mobility inside nuclei, PCNA is dynamically presented in a soluble or chromatin
      associated form. The heterogeneity and specific modifications of PCNA may reflect
      its multiple functions and the presence of many binding partners in the cell. The
      recent proteomics approaches applied to characterizing PCNA interactions revealed
      multiple PCNA partners with a wide spectrum of activity and unveiled the possible
      existence of new PCNA functions. Since more than 100 PCNA-interacting proteins
      and several PCNA modifications have already been reported, a proteomics point of
      view seems exactly suitable to better understand the role of PCNA in cellular
      functions.

PMID- 18726184
TI  - Asymptomatic cerebellopontine angle and lateral ventricle metastases from renal
      cell carcinoma: case report and literature review.
AB  - Tumors rarely metastasize to the cerebellopontine angle. We report the first
      instance of simultaneous metastasis of renal cell carcinoma to the
      cerebellopontine angle and the lateral ventricle. A 51-year-old man presented
      with anemia and fatigue owing to stomach metastases from renal cell carcinoma 8
      years after undergoing partial left nephrectomy for grade II clear cell renal
      carcinoma and radical right nephrectomy for grade III clear cell renal carcinoma.
      He also suffered metastases to the lung, both adrenal glands, the L-3 vertebra,
      and the brain (asymptomatic, but revealed by magnetic resonance imaging): a 1-cm
      (maximum diameter) mass in the left medullary cistern and a 2-cm (maximum
      diameter) mass in the right lateral ventricle trigone. Both brain lesions were
      treated with stereotactic radiosurgery, followed by gross-total resection of the
      right trigonal mass 7 months later. Both tumors shrank significantly, but the
      patient died from progressive systemic cancer 1 year after diagnosis of brain
      metastasis.

PMID- 18726182
TI  - Molecular physiology of mammalian glucokinase.
AB  - The glucokinase (GCK) gene was one of the first candidate genes to be identified
      as a human "diabetes gene". Subsequently, important advances were made in
      understanding the impact of GCK in the regulation of glucose metabolism.
      Structure elucidation by crystallography provided insight into the kinetic
      properties of GCK. Protein interaction partners of GCK were discovered. Gene
      expression studies revealed new facets of the tissue distribution of GCK,
      including in the brain, and its regulation by insulin in the liver. Metabolic
      control analysis coupled to gene overexpression and knockout experiments
      highlighted the unique impact of GCK as a regulator of glucose metabolism. Human
      GCK mutants were studied biochemically to understand disease mechanisms. Drug
      development programs identified small molecule activators of GCK as potential
      antidiabetics. These advances are summarized here, with the aim of offering an
      integrated view of the role of GCK in the molecular physiology and medicine of
      glucose homeostasis.

PMID- 18726185
TI  - Immune mediated neurologic dysfunction as a paraneoplastic syndrome in renal cell
      carcinoma.
AB  - OBJECTIVE: To describe a case of cerebellar ataxia associated with renal cell
      carcinoma. CASE REPORT: A 53-year-old Caucasian male with a history of
      Schizophrenia presented with generalized weakness, nausea, vomiting, severe
      weight loss, and progressively worsening gait difficulty associated with multiple
      falls. Physical examination revealed profound ataxia with inability to ambulate
      despite normal strength. The patient also appeared cachectic. A contrast-enhanced
      CT of the abdomen/pelvis showed a 10.4 x 8.3 cm(2) left renal mass.
      Histopathology of the tissue revealed morphology consistent with renal cell
      carcinoma. Paraneoplastic antibodies including anti-Hu, anti-Ma, anti-Ri, and
      anti-Yo were negative, however, biotinylated serum analysis was positive for
      hippocampal and cerebellar Purkinje cells. DISCUSSION: The pathogenesis of
      paraneoplastic neurological syndromes is believed to be associated with antibody
      and T-cell mediated response to antigens shared between the tumor and neural
      tissue. Though serum from this patient was negative for well-characterized
      antibodies, further testing revealed the presence of proteins binding to the
      hippocampal region of the midbrain and the cerebellum, and to components of the
      extracellular matrix of the tumor which may suggest partially characterized or as
      yet uncharacterized antibodies directed against renal cell tumor tissue and the
      nervous system. This possibility is supported by the observed symptom resolution
      upon tumor resection. The described case introduces a possible association
      between an antibody, which may be specific to paraneoplastic neurological
      syndromes, and renal cell carcinoma.

PMID- 18726186
TI  - Acute infarction of meningioma demonstrated by diffusion-weighted MR imaging.

PMID- 18726187
TI  - Corrosion resistance evaluation of a Ca- and P-based bioceramic thin coating in
      Ti-6Al-4V.
AB  - The objective of this study was to physico/chemically characterize and determine
      the corrosion resistance of a Calcium-Phosphate (Ca-P) based bioceramic thin
      coating processed by a sputtering process on titanium alloy (Ti-6Al-4V). The
      samples utilized in this study were uncoated and coated disks of 10 mm diameter
      by 3 mm thickness. The coating was characterized by SEM, XPS + ion beam milling
      (IBM), thin-film mode XRD, and atomic force microscope (AFM) (n = 3). Coated and
      uncoated Ti-6Al-4V disk surfaces were tested in Phosphate Buffered Saline (PBS)
      at 25 degrees C through an area of 0.79 cm(2). A three-electrode cell set-up was
      used with a saturated calomel electrode (SCE) and a platinum wire as reference
      and counter electrodes. After 3, 17, and 25 days of immersion, electrochemical
      impedance spectroscopy (EIS) experiments were performed (n = 3). The EIS tests
      were carried out in potentiostatic mode at the open circuit potential (OCP). The
      frequency range considered was from 100 kHz to 10 mHz, using 10 mV root mean
      square as the amplitude of the perturbation signal. A potentiodynamic
      polarization scan using a frequency response analyzer potentiostat, was acquired
      following 3 days of immersion in PBS. The potentiodynamic polarization scans (n =
      3) were carried out with a scan rate of 1 mV/s ranging from -0.8V(SCE) to
      3.0V(SCE). RESULTS: The physico/chemical characterization showed an amorphous Ca-
      and P-based coating of approximately 400-700 nm thickness with Ca-P nanometer
      size particles embedded in a Ca-P matrix. The Bode phase angle diagrams showed
      highly capacitive results at low and medium frequencies for both surfaces tested.
      The polarization curves showed low current densities at the corrosion potential
      (E (corr)), in the order of 10(-8)A/cm(2), typical of passive materials with
      protective surface films. Coated sample current densities were comparable to the
      uncoated samples. CONCLUSION: Coated and uncoated samples were stable in the test
      solution with a protective film maintained throughout the 25 day immersion test
      period.

PMID- 18726188
TI  - Vesicular stomatitis virus matrix protein gene enhances the antitumor effects of
      radiation via induction of apoptosis.
AB  - Vesicular stomatitis virus (VSV) matrix (M) protein can directly induce apoptosis
      by inhibiting host gene expression when it is expressed in the absence of other
      viral components. Previously, we found that the M protein gene complexed to DOTAP
      cholesterol liposome (Lip-MP) can suppress malignant tumor growth in vitro and in
      vivo; however, little is known regarding the biological effect of Lip-MP combined
      with radiation. The present study was designed to determine whether Lip-MP could
      enhance the antitumor activity of radiation. LLC cells treated with a combination
      of Lip-MP and radiation displayed apparently increased apoptosis compared with
      those treated with Lip-MP or radiation alone. Mice bearing LLC or Meth A tumors
      were treated with intratumoral or intravenous injections of Lip-MP and radiation.
      The combined treatment significantly reduced mean tumor volumes compared with
      either treatment alone in both tumor models and prolonged the survival time in
      Meth A tumor models and the intravenous injection group of LLC tumor models.
      Moreover, the antitumor effects of Lip-MP combined with radiation were greater
      than their additive effects when compared with the expected effects of the
      combined treatment in vivo. This study suggests that Lip-MP enhanced the
      antitumor activity of radiation by increasing the induction of apoptosis.

PMID- 18726189
TI  - Mathematical modeling identified c-FLIP as an apoptotic switch in death receptor
      induced apoptosis.
AB  - Apoptosis is an essential process to get rid of injured or unwanted cells. In
      this study, we proposed a mathematical modeling for death receptor mediated
      apoptosis to investigate the role of c-FLIP in controlling the balance between
      apoptosis and survival. In order to get insight into how NF-kappa B mediated pro
      survival pathway affects the outcome of our modeling, we implemented reduced
      models without taking such regulation into consideration. Our simulation revealed
      that c-FLIP could act as a pivotal death or life switch and this switch-like
      behavior is bistable, irreversible, and robust. We introduce a new term,
      probability apoptosis, to delineate the likelihood in occurrence of apoptosis
      events. This simulation system is plausible and may offer several valuable
      clinical indications for the abnormal apoptosis related disease, such as cancer.

PMID- 18726190
TI  - Lupulone, a hop bitter acid, activates different death pathways involving
      apoptotic TRAIL-receptors, in human colon tumor cells and in their derived
      metastatic cells.
AB  - Our study aimed to compare death signalling pathways triggered by lupulone in
      TRAIL-sensitive human colon cancer cells (SW480) and in their derived TRAIL
      resistant metastatic cells (SW620). Lupulone (40 microg/ml) up-regulated
      expression of TRAIL DR4/DR5 death receptors at the cell surface of both cell
      lines, even in the absence of exogenous TRAIL ligand. Cell death induced by
      lupulone was inhibited in SW480 and SW620 cells exposed to blocking anti-DR4/DR5
      antibodies. In SW480 cells, lupulone triggered cell death through a cross-talk
      between TRAIL-DR4/DR5 and the mitochondrial (intrinsic) pathways involving
      caspase-8 activation and Bid protein cleavage. As a consequence mitochondrial
      cytochrome c was released into the cytosol and activation of caspases-9 and -3
      was observed. In the metastatic SW620 cells, lupulone restored the sensibility of
      these cells to TRAIL ligand and activated the extrinsic apoptotic pathway via
      DR4/DR5 death receptors and the involvement of the caspase-8/caspase-3 cascade.
      The demonstration that lupulone is able to activate TRAIL-death signalling
      pathways even in TRAIL resistant cancer cells highlights the potential of this
      natural compound for cancer prevention and therapy.

PMID- 18726191
TI  - Selected markers of proliferation and apoptosis in the parathyroid lesions: a
      spatial visualization and quantification.
AB  - The aim of the paper was to apply a method for quantitative assessment of
      proliferation and apoptosis markers, based on their 3D visualization, in cases of
      parathyroid adenoma and hyperplasia. Material was obtained from 49 patients (32
      females and 17 males) with primary hyperparahyroidism. Quantitative
      immunohistochemistry studies of Ki-67, proliferating cell nuclear antigen (PCNA)
      and bcl-2 were performed on digital microscopy images with the use of 3D
      visualization. The use of spatial visualization method allowed us to perform
      objective quantitative assessment of the studied immunohistochemical markers. The
      average cell nuclear fraction of Ki67+ was 1.8% in hyperplasia and 1.9% in
      adenoma cases while 3.5% in the controls. The highest expression of PCNA was
      found in parathyroid hyperplasia (22.9%) and significantly decreased in adenoma
      (12.5%) and in the control group (16.8%). The lower expression of bcl-2 in
      hyperplasia cases (mean area fraction of 0.172 per 1 mum(2), in contrast to 0.643
      in adenomas and 0.648 in control) suggested that principal cells can be ready for
      apoptosis and may confirm the important role of bcl-2 protein in etiopathogenesis
      of hyperplasia of the parathyroid gland while PCNA might be a useful marker for
      differentiating adenoma from early hyperplasia in primary hyperparahyroidism
      cases.

PMID- 18726192
TI  - Strategies for the identification of loci responsible for the pathogenesis of
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic, debilitating disease, which manifests
      itself by de-myelination of the central nervous system (CNS). MS is predominantly
      found in Caucasians of European decent and is more prominent in females than
      males. MS is one of the most prevalent causes of disability of young adults in
      the world. The exact cause of MS is not known, however genetic susceptibility to
      MS is linked to the major histocompability complex (MHC). Self reactive CD4+ T
      cells, specific for CNS antigens, such as myelin basic protein (MBP), myelin
      oligodendrocyte glycoprotein (MOG) and proteolipid protein (PLP), are detectable
      in MS patients along with pathogenic autoantibodies specific to these CNS
      antigens produced by B cells. These observations suggest that MS is an autoimmune
      disease. Epidemiology of MS along with the analysis of sibling pairs and twins
      suggest that the multiple genetic factors and their interaction with environment
      contribute to disease susceptibility. Recent developments and advancements in
      genetic analysis may aid in accurate determination of genetic risk factors for
      the development of MS. We review these developments, advances in technology and
      discuss recent results in this article.

PMID- 18726193
TI  - Expression and secretion of barley alpha-amylase and A.niger glucoamylase
      inSaccharomyces cerevisiae.
AB  - cDNAs of barley alpha-amylase andA. niger glucoamylase were cloned in oneE. coli
      yeast shuttle plasmid resulting in the construction of expression secretion
      vector pMAG15. pMAG15 was transformed intoS. cerevisiae GRF18 by protoplast
      transformation. The barley alpha-amylase andA. niger glucoamylase were
      efficiently expressed under the control of promoter and terminator of yeast PGK
      gene and their own signal sequence. Over 99% of the enzyme activity expressed was
      secreted to the medium. The recombinant yeast strain, S.cerevisiae GRF18
      (pMAG15), hydrolyzes 99% of the starch in YPS medium containing 15% starch in 47
      h. The glucose produced can be used for the production of ethanol.

PMID- 18726194
TI  - Expression of truncated and fused green fluorescent protein genes and analysis of
      their properties.
AB  - The green fluorescent protein (GFP) of the jellyfishAequorea victoria is an
      unusual protein with strong visible absorbance and fluorescence from a
      chromophore, which is generated by cyclization and oxidation of the protein's own
      Ser-Tyr-Gly sequence at position 65-67. The mutant of Ser65 to Thr gives
      fluorescence intensity sixfold greater than that of the wild type. Several
      expression vectors containing different truncated lengths or chimericgfp genes
      were introduced. The relationship between the structure and fluorescence
      properties of GFP was discussed.

PMID- 18726195
TI  - Molecular evidence on maize specific DNA fragment transferred into wheat through
      sexual hybridization.
AB  - Nearly 100 maize-specific repeated DNA clones were screened from a maize random
      genomic library, and used for RFLP analysis of two wheat DH populations from
      wheat and maize crosses. The result showed that a maize fragment in clone MR64
      was transferred into two wheat DH lines, i.e. No. 18 in common wheat DHs and No.
      15 in persicum wheat DHs, in which strong hybridization signals were detected. It
      is first proved at DNA level that some maize-specific DNA can be transferred into
      wheat DH progenies through fertilization at low frequency. Sequencing revealed
      that the size of the cloned insert DNA is 695 bp, containing 58% A + T. Southern
      hybridization to maize genome with several restriction enzymes indicated that
      MR64 is a dispersed repeat with 2-3 dominant tandem units. Its sequence
      structure, methylation pattern, copy number and chromosomal distribution were
      also determined. The possible mechanism of alien DNA transfer was discussed.

PMID- 18726196
TI  - Energy transfer kinetics of phycoerythrocyanin trimer from cyanobacteriumAnabaena
      variabilis (II).
AB  - The excitation energy transfer processes in trimeric PEC have been studied by
      using steady-state and time-resolved fluorescence spectra techniques in detail.
      The results indicate that the energy transfer processes should take place between
      alpha(84)-PVB and beta(84)-or beta(155)-PCB chromophores with the time constants
      34.7 ps and 175-200 ps individually; in contrast with monomeric PEC, from time
      resolved fluorescence anisotropic spectrum technique, the decay constant of 45 ps
      which was assigned to the energy transfer time among three beta(84)-PCB
      chromophores was observed and the energy levels of beta(84)-and/or beta(155)-PCB
      chromophores were confirmed to turn over in trimeric PEC.

PMID- 18726197
TI  - Expression of tachykinin receptors inXenopus oocytes injected with poly (A)(+)
      RNA from cat dorsal root ganglion.
AB  - The expression of the types of tachykinin receptors in the dorsal root ganglion
      (DRG) neurons by means ofXenopus oocyte expressing system was studied. Poly(A)(+)
      RNAs were extracted from cat cervical and lumbar DRG. Two days after injection of
      Poly (A)(+) RNAs, the oocytes were recorded with the two-electrode voltage clamp
      technique. In the oocytes injected with DRG poly(A)(+) RNA, [Sar(9),
      Met(O(2))(11)]-substance P(Sar -SP, 1 mumol/L), neurokinin A (NKA, 1 mumol/L) or
      [beta-Ala(8)]-neurokinin A((4-10)) (Ala-NKA, 1 mumol/L) produced an inward
      current comprising a rapid spike and a long sustained oscillatory component for
      several minutes. Sar-SP induced response was blocked by NK-1 antagonist L-668,
      169 (1 mumol/L), but not by NK-2 antagonist L-659, 877(1mumol/L). In contrast,
      Ala-NKA and NKA responses were only blocked by L-659, 877. The oocytes injected
      with DH Poly(A)(+)RNA also responded to Sar-SP and NKA with similar inward
      currents, which were selectively blocked by L-668, 169 and L-659, 877,
      respectively. These tachykinins-induced responses had a potent desensitization.
      The present data indicate expression of NK-1 and NK-2 receptors in DRG neurons,
      suggesting that there may be tachykinin autoreceptors on the nociceptive primary
      afferent terminals.

PMID- 18726198
TI  - Injecting skin fibroblasts into muscles to express human clotting factor IX cDNA.
AB  - Primary rabbit skin fibroblasts (RSF) containing lacZ reporter gene or human
      clotting factor IX (hFIX) cDNA could long-termly exist and be expressed after
      being implanted in rabbit muscles. Among them, the beta-glactosidase expression
      lasted at least 3 months, and hFIX expression lasted 1 month. These results will
      be helpful to organically combine the advantages of both skin fibroblasts and
      muscle, and provide a new way for somatic gene therapy of hemophilia B and other
      genetic diseases.

PMID- 18726199
TI  - Possibility of biological micromachining used for metal removal.
AB  - Besides the physical and chemical machining methods, a biological machining
      method has been presented. The experimental results show that machining of pure
      iron, pure copper and constantan by a special bacterium,Thiobacillus
      ferrooxidans, was possible. A micro gear and grooves on pure copper piece were
      bio-machined. The depth of the groove so bio-machined was directly dependent on
      the machining time. The biomachining mechanism has been analyzed from the
      electron-transport chain (ETC) in the T.ferrooxidans membrane, and its developing
      direction has been also discussed.

PMID- 18726200
TI  - Binding of activator SyrM to the site ofnodD3 P1 region ofRhizobium meliloti.
AB  - The nodD3 gene ofRhizobium meliloti is transcribed via promoter P1 or P2. Gel
      retardation assay showed binding of SyrM to the P1 upstream region of nodD3.
      DNaseI footprint analysis demonstrated that the binding site of SyrM in nodD3 P1
      region consists of two inverted repeat sequences arranged in tandem. SyrM seems
      to bind to DNA in the form of dimer or tetramer and requires the two inverted
      repeat sequences for binding.

PMID- 18726201
TI  - Monoclonal antibody, a novel probe for protein folding.
AB  - Two monoclonal antibodies (McAb2C9, McAb1E5) against Staphylococcal nuclease R
      (SNase R) and its N-terminal peptide fragments were prepared, purified and
      characterized. Further studies show that the intact enzyme SNase R and its seven
      N-terminal peptide fragments differ in their interaction with McAb2C9. SNase R,
      SNR121, SNR102, SNR79 and SNR52 can bind to McAb2C9 readily, while fragments of
      SNR141, SNR135, SNR110 react with the antibody poorly. If this difference is due
      to diverse extent of exposure of the specific epitope in the fragments, it is
      suggested that the conformation of the peptide is subjected to continuous
      adjustments through chain elongation until the biologically active protein is
      formed. This result supports Tsou's hypothesis of nascent peptide folding
      experimentally.

PMID- 18726202
TI  - Plasmalemma hyperpolarity and culture of sense and antisenseabp transgenic
      tobacco protoplasts.
AB  - The relationship among transfer and expression of auxin binding protein gene
      (abp), auxin (NAA)-induced plasmalemma hyperpolarity and sensibility to auxin
      during protoplast culture was studied by measuring transmembrane potential
      difference (Em) and culturing the protoplasts of sense and antisenseabp
      transgenic tobacco. The concentration of NAA inducing the highest degree of
      hyperpolarity of senseabp transgenic tobacco protoplasts was lower than the
      control, and in protoplast culture, their sensibility to auxin increased. The
      concentration of antisenseabp transgenic tobacco protoplasts was higher than the
      control, and in protoplast culture, their sensibility to auxin decreased. These
      results demonstrated that ABP synthesized in endoplasmic reticulum needed to
      transport to cell membrane and functioned there.

PMID- 18726203
TI  - N-glycosidase mechanism of Trichosanthin.
AB  - The interactions between TCS and AMP, ADO, TUB., CMP were studied by
      crystallographic method, which confirmed that TCS specially recognizes ADE, but
      does not recognize cytosine. When TCS interacts with mononucletide, the ligand
      with or without phosphate is not important. The proton H(+) of guanidinum group
      of Arg163 is shared by N(3) of ADE, but is not received by N(7). This enriches
      the model of N-glycosidase mechanism about TCS and AMP. This model should suit to
      the interaction between RIPs and AMP, and reflect the main interaction between
      RIPs and rRNA. However, the interaction between RIPs and rRNA is more
      complicated. To comprehensively understand recognition and catalysis of RIPs
      against rRNA, at least the RIP/RNA segment complex crystal structure should be
      determined. This RNA segment should contain stem and loop with GAGA sequence.

PMID- 18726204
TI  - Identification and characterization of scaffold-associated region (SAR) of rRNA
      gene of silkwormAttacus ricini.
AB  - identify the specific nuclear scaffold-bound DNA sequence in rRNA gene clusters
      of silkwormAttacus ricini, the detergent-like salt lithium 3', 5'
      diiodosalicylate (LIS) was used for the preparation of nuclear scaffold. Through
      Southern hybridization, using different DNA stretches of rRNA gene as the probe,
      a scaffold-associated region (SAR) in the 5-non transcribed spacer (NTS) of rRNA
      gene has been identified. Exonuclease III digestion was used to narrow down the
      sequence of matrix attachment fragment. It was defined as a specific attachment
      site within the SacII-EcoRI fragment. It is about 1 kb in length and AT-rich (>
      70%). Computer analysis of the SAR sequencing data showed that there are
      topoisomerase II cleavage sites, ATATTT box, and yeast autonomously replication
      sequence (ARS). The d(AT)(18) specific DNA sequence of the SAR, which was
      determined previously, was an S1 nuclease hypersensitive site. It might be a cis
      element of DNA-signal characteristic for SAR.

PMID- 18726205
TI  - Membrane molecules in induction of apoptosis of thymocytes by mouse thymic
      dendritic cells which express Fas ligands.
AB  - Apoptosis of thymocytes is involved in the negative selection of thymus, but it
      remains unclear how the cell death of thymocytes is regulated by the thymic
      stromal cells. By using immunohistochemistry, TdT-mediated dUTP nick end labeling
      (TUNEL) and flow cytometry methods, it was found that Fas ligand was expressed in
      the thymic medulla and a mouse thymic medullary type dendritic cell line (MTSC4).
      The DNA fragmentation and TUNEL positive staining of thymocytes were detected in
      6 h of cocultures with MTSC4. 97 % of the thymocytes which bound to MTSC4 were
      Fas antigen positive cells. The DNA fragmentation of thymocytes induced by MTSC4
      was inhibited by the addition of 20 mmol/L N-acetyl galactosamin monosaccharide
      and the pretreatment of a monoclonal antibody (PF-18-3) which recognized a
      putative antigen on MTSC4. These results suggested that the mechanisms of
      induction of cell death by stromal cells may include the interactions of multiple
      cell surface molecules, in addition to the Fas/Fas ligand system.

PMID- 18726206
TI  - Biophysical meanings of orientation and deformation of RBCs in shear flow field
      of low viscosity with new Ektacytometry.
AB  - The rheological behavior of RBCs treated with WGA of different concentrations was
      measured by the recently developed new Ektacytometry method in suspending medium
      of low viscosity. The biophysical meanings of the orientation index (DI)(or) and
      the small deformation index (DI)(d) in the new Ektacytometry were explained by
      comparison with the results using the fluorescence polarization technique and the
      electron spin resonance technique (ESR).

PMID- 18726207
TI  - Effect of mouse thymic medullary epithelial cell line on thymocyte development
      and functional maturationin vivo.
AB  - Thymic medullary type epithelial cell line (MTEC1), which expressed H-2D(d) and
      Ia(d), was derived from BALB/c mouse. MTEC1 cells were introduced by intrathymic
      injection into irradiated H-2(b) mice reconstituted with H-2(bxd) F1bone marrow
      cells. Two months later, the injected MTEC1 cells were found to be still present
      in the recipient thymus. Splenocytes from chimeric mice, inin vitro functional
      assays, were analyzed to investigate whether the MTEC1 cellsin vivo could induce
      the production of H-2(d) restricted antigen-specific T cells. The H-2(d)
      restricted VSV-antigen specific proliferating and IL-2 producing T cells as well
      as H-2(d) restricted influenza virus specific cytotoxic T cells were found in
      chimeric mice injected with MTEC1 cells, and these cells were shown to be
      tolerant to H-2(d) selfantigen. On the contrary, H-2(d) restricted antigen
      specific and H-2(d) self-antigen tolerant T cells were not shown in control mice
      injected with saline. These results suggest that intrathymically injected MTEC1
      cells could induce T lineage cell development and functional maturation in the
      intact thymus. A hypothesis of "second thymic selection" in thymic medulla has
      been postulated and its implication discussed.

PMID- 18726209
TI  - mRNA differential display between sterile and fertile anther of rice and analysis
      of cDNA differential fragments.
AB  - Rice anther and leaf mRNAs from two cytoplasmic male sterile lines (Maxie A and
      Congguong 41A) were compared with those from their maintainers and F(1) hybrids
      by using mRNA differential display to study gene expression pattern in sterile
      anther during pollen abortion. Anther cDNA differential bands between sterile and
      fertile plants were more than those of leaf. It was indicated that the expression
      of fertility gene(s) in the anther was more activable and sufficient than in the
      leaf. The gene transcript pattern in one of different types of anther was not
      only associated with its pollen sterility degree but also with its stage of
      pollen abortion. The anthers with full or partial sterility or with early
      abortion produced more cDNA differential bands than those fertile or late
      abortion anthers. In twelve recovered differential cDNA fragments, two were
      probably associated with male sterility, i. e. one is (AB(4)A(5)), which was
      specifically expressed in the sterile anther, and the other (AB(3)B(2)), which
      contained some sequence homologous to a mitochondrial gene (coxII) and whose
      expression was partially suppressed in the sterile anther.

PMID- 18726208
TI  - An ABA-binding protein with nucleic acid-binding property.
AB  - Maize cDNA expression library was screened using the antibodies against ABA
      binding proteins (ABBP). From 200 000 separated phage plaques, only one cDNA
      clone coding for a polypeptide was obtained. It shows 60%-65% homology to the
      genes of nucleic acid-binding proteins in mammalia. However, about 120 cDNA
      clones coding maize 17s rRNA were unexpectedly obtained. In view of this, the
      ABBP purified by ABA affinity chromatography and the antibodies derived from the
      purified ABBP were examined. It is found that rRNA is indeed present in the ABBP.
      In addition, the obtained antibodies could recognize RNA as well as ABBP. It is
      suggested that the ABBP have nucleic acid-binding property and can form a complex
      with rRNA.

PMID- 18726210
TI  - Structural and functional analysis of a MADS box containing genomic DNA sequence
      cloned from rice.
AB  - A putative MADS box gene (RgMADS1) was cloned by screening a rice genomic library
      with a heterogeneous MADS box probe derived from Antirrhinum majus squamosa gene.
      Sequencing and Southern analysis showed that RgMADS1 contains a highly conserved
      MADS box sequence, - whereas the rice genome contains numbers of MADS box genes.
      A chimera gene of RgMADS1 under the control of CaMV 35S promoter was constructed
      and used to transform Arabidopsis. Some transformants exhibited abnormal
      phenotypes in their flowers, which were reflected in the floral structure, number
      and setting position. Therefore, RgMADS1 is likely a member of rice MADS box gene
      family and may be involved in the floral establishment and function control in
      the rice developmental process.

PMID- 18726211
TI  - Cloning of alpha-amylase gene from Schwanniomyces occidentalis and expression in
      Saccharomyces cerevisiae.
AB  - The cloning of alpha-amylase gene of S. occidentalis and the construction of
      starch digestible strain of yeast, S. cerevisiae AS. 2. 1364 with ethanol
      tolerance and without auxotrophic markers used in fermentation industry were
      studied. The yeast/E. coli shuttle plasmid YCEp1 partial library of S.
      occidentalis DNA was constructed and alpha-amylase gene was screened in
      S.cerevisiae by amylolytic activity. Several transformants with amylolysis were
      obtained and one of the fusion plasmids had an about 5.0 kb inserted DNA
      fragment, containing the upstream and downstream sequences of alpha-amylase gene
      fromS. occidentalis. It was further confirmed by PCR and sequence determination
      that this 5.0 kb DNA fragment contains the whole coding sequence of alpha
      amylase. The amylolytic test showed that when this transformant was incubated on
      plate of YPDS medium containing 1% glucose and 1% starch at 30 degrees Celsius
      for 48 h starch degradation zones could be visualized by staining with iodine
      vapour. alpha-amylase activity of the culture filtratate is 740-780 mU/mL and
      PAGE shows that the yeast harboring fusion plasmids efficiently secreted alpha
      amylase into the medium, and the amount of the recombinant alpha-amylase is more
      than 12% of the total proteins in the culture filtrate. These results showed that
      alpha-amylase gene can be highly expressed and efficiently secreted inS.
      cerevisiae AS. 2.1364, and the promotor and the terminator of alpha-amylase gene
      fromS. occidentalis work well inS. cerevisiae AS. 2.1364.

PMID- 18726212
TI  - Auditory response and intrinsic link with sound-production in singing male
      cicada.
AB  - In the black cicada (C. atrata Fabricius), the quiescent males are sensitive to
      stimulating sound-pulses of about 70 dB (SPL); the latent periods and amplitudes
      of compound action potentials of the auditory nerve (called "auditory nerve
      potential (AP)" for short) which are corresponding one by one to stimulating
      sound-pulses are (3.92 +/-0.28) ms and (0.32+/-0.22) mV on an average,
      respectively. Although the singing males are nonreactive to outside stimulating
      sound-pulses, they are still sensitive to calling pulses mingling in stimulating
      sound-pulses; the latent periods and amplitudes of auditory nerve potentials are
      (4.16 +/- 0.43) ms and (0.46 +/- 0.25) mV, respectively. In singing males the
      negative potential before each auditory nerve potential characterizes that the
      intrinsic link exists between sounding and auditory nerve system.

PMID- 18726213
TI  - A mechanism underlying stimulation and inhibition of protein kinase C by lyso-PC:
      A role of membrane physical state.
AB  - Lysophosphatidylcholine (lyso-PC) biphasically regulates the diacylglycerol
      induced activation of protein kinase C (PKC). In common parlance, lyso-PC
      stimulates PKC at low concentrations, but, conversely, inhibits it at high
      concentrations. The activity of purified PKC from rat brains was measured in the
      vesicles made up of dipalmitoylphosphatidylserine (DPPS), 1, 2-sn-diolein (DOG)
      and different molar ratios of 1-palmitoyl-sn-glycerol-3-phosphoryl-choline (C16:0
      lyso-PC). The effect, i. e. stimulation or inhibition on PKC by C16:0 lyso-PC,
      depends on DPPS and DOG concentrations as well as its own concentration. When the
      concentration of DOG is stable, this C16:0 lyso-PC action depends on C16:0 lyso
      PCIDPPS molar ratio. Differential scanning calorimetry (DSC), two fluorescence
      probes and light scattering were used to analyze the physical characteristics of
      membrane, including thermotropic phase behavior, the turbidity, the lipid
      molecular acyl chains packing and the head group spacing. The more adulteration
      of C16:0 lyso-PC in liposome bilayer membrane, the looser acyl chains pack, and
      the broader head group spacing. DSC results show that there are two immiscible
      lipid areas in the membrane: C16:0 lyso-PC-rich area and C16: 0 lyso-PC-poor
      area. When C16:0 lyso-PC/DPPS molar ratio was 0.234, the two areas had the
      broadest boundary and the activation of PKC was the highest. When the ratio was
      over 0.434, the phase transition of DPPS disappeared; micelle tended to
      substitute the structure of bilayer; the activity of PKC was inhibited
      completely. DOG can stabilize the bilayer structure of membrane, so the C16:0
      lyso-PC/DPPS molar ratios to inhibit PKC in lipid mixture with DOG are higher
      than that without DOG. The ability of C16:0 lyso-PC to change the physical
      properties and the structure of membrane plays an important role in its effect on
      PKC activation.

PMID- 18726214
TI  - NodD binds to target DNA in isologous octamer.
AB  - NodD, the major regulatory protein of nodulation, was partially purified from
      Rhizobium leguminosarum 8401(pIJ1518), and its binding sequences within nodF
      promoter of R. l. bv. viciae were determined by DNase I footprinting. A series of
      techniques based on gel retardation were used to analyze the NodD-target DNA
      interaction, showing that NodD binds to target DNA in isologous octamer.

PMID- 18726216
TI  - Raman spectroscopic study of space structure of membrane proteins and membrane
      lipids in photodamaged human erythrocyte sensitized by hypocrellin B.
AB  - Laser Raman spectroscopy was used to investigate the photodamage characteristics
      of human erythrocyte membranes sensitized by hypocrellin B (HB) at the molecular
      level. It brought to light that the essence of the changes of erythrocyte
      membranes' functions caused by membrane protein cross-linking and membrane lipid
      peroxidation, including increase of fluidity and ion permeability of membranes,
      etc., was that the orderly structure of erythrocyte membranes had been damaged by
      the active oxygen ((1)O(2), O(2)(-) and, OH) generated by HB, including the
      decrease of alpha-helix, beta-sheet and the increase of random coil in the main
      chain of membrane proteins, the decrease of mercapto groups, indole rings, p
      hydroxy phenyl rings, monosubstituted phenyl rings, etc. in the side-chain, and
      the changes of the conformations of membrane lipids as well. With the increase of
      the irradiation time, the trans conformation of membrane lipids increased first,
      then decreased. On the contrary, the gauche conformation decreased first, then
      increased. In addition, the decrease of the intensities of the lines assigned to
      bending vibration of the conformation-insensitive CH(2) and CH(3) of membrane
      proteins and lipids suggested that break of their chains had occurred.

PMID- 18726215
TI  - Role of calcium in apoptosis of HL-60 cells induced by harringtonine.
AB  - The effect of Ca(2+) on HT-induced apoptosis in HL-60 cells was examined.
      Characteristics of apoptosis induced by harringtonine (HT) or campothecin (CAM)
      could not be abolished by extracellular calcium chelator EGTA; however, an
      intracellular Ca(2+) chelator BAPTA-AM could block HT or CAM-induced HL-60 cell
      apoptosis. Requirement of intracellular calcium for HT-induced apoptosis is
      further supported by the fact that intracellular Ca(2+) -depleted HL-60 cells
      could not undergo HT-induced apoptosis. No significant increase of intracellular
      Ca(2+) was found after HT treatment. By using video enhancement contrast
      microscopy (VEC), the dynamic changes of intracellular calcium distribution over
      the whole period of apoptosis in the same individual cell were detected. The
      results demonstrated the movement of Ca(2+) from cytosol to nucleus after
      initiation of apoptosis by treatment with HT.

PMID- 18726217
TI  - Isolation and mapping of bacterial artificial chromosome (BAC) clone containing
      telomere-associated sequence.
AB  - Using single primer (TTTAGGG)(3) or (CCCTAAA)(3)CCC corresponding to rice
      telomeric repeat sequences, two fragments were amplified from rice genomic DNA
      and named Tas1 and Tas2. These two fragments did not show polymorphism between
      the mapping parents. Tasl was found to hybridize to rice telomeric regions by in
      situ hybridization (FISH). Then a rice bacterial artificial chromosome (BAC)
      library was constructed and Tasl was used to screen it. One positive clone was
      identified. A single copy sequence of this BAC clone was mapped at the end of the
      6th chromosome of rice.

PMID- 18726218
TI  - Sox and Zfx genes in giant panda.
AB  - By using PCR cloning techniques, the DNA sequences of the HMG box regions of six
      Sox genes (pSox) and the zinc finger domains of two Zfx genes (pZfx) in the giant
      panda were identified. The giant panda Sox genes fell into two subfamilies, SOX
      S1 and SOX-S2. The pSox and pZfx genes of the giant panda were highly homologous
      to the corresponding genes in mammals and revealed close substitution rates to
      those in the primates.

PMID- 18726219
TI  - Isolation and partial molecular characterization of heat-stable growth factor
      from human placenta.
AB  - A heat-stable growth factor has been purified to homogeneity from human placenta.
      Purification procedure involved extraction with acidic medium, precipitation
      using ethanol, DE-52 ion-exchange chromatography, and reversed-phase HPLC. The
      purified preparation has been named human placental growth factor-1 (HPGF-1),
      which simulates the proliferation of some cell lines, such as human amniotic
      cell, mouse marrow tumor cell, and mouse fibroblast cell. The growth factor has
      an approximate molecular weight of 1 900. It is a glycopeptide which contains a
      polypeptide chain consisting of 10 amino acid residues with molecular weight of 1
      195. The N-terminal residue of the polypeptide chain part is phenylalanine. The
      molecular weight of non-peptide part is 682. The isoelectric point of the growth
      factor is pI 6.8.

PMID- 18726220
TI  - Cloning and expression of 5, 10-Methylenetetrahydrofolate reductase (MTHFR) gene.
AB  - Hyperhomocysteinemia is an independent risk factor of cardiovascular diseases and
      birth defects. One of the important factors causing hyperhomocysteinemia is
      decrease of 5,10-Methylenetetrahydrofolate reductase. Human and rat MTHFR cDNAs
      with RT-PCR were isolated, a prokaryodytic expression vector containing human
      MTHFR cDNA was constructed, and human MTHFR protein was expressed inE. coli. It
      was also found that the expression of rat MTHFR could be promoted by IL-1 and
      homocysteine.

PMID- 18726221
TI  - Application of radiation hybrid in gene mapping.
AB  - Radiation hybrid (RH) mapping technique was exploited to determine chromosome
      locations of 26 human novel full length cDNAs recently cloned. All these cDNA
      clones were isolated from human cord blood CD (+) (34) cells and may be related
      to regulation of hematopoiesis. 23 genes were successfully mapped to chromosomal
      positions, while RH analyses were not possible in the remaining 3 cases. RH
      technique is indeed a powerful tool for mapping novel cDNA sequences due to its
      rapidity, precision, convenience and reproducibility.

PMID- 18726222
TI  - Nicotinic acetylcholine receptor is involved in acetylcholine regulating stomatal
      movement.
AB  - In animal cells, actions of acetylcholine depend on its binding to specific
      receptors. Activation of nicotinic acetylcholine receptor can affect the membrane
      permeability to ions directly. As concerned about acetylcholine regulating
      stomatal movement, nicotinic acetylcholine receptor may also be involved.
      Experiments with nicotinic acetylcholine receptor antagonist (D-tubocurarine) and
      agonist (nicotine) showed that nicotinic acetylcholine receptor was involved in
      acetylcholine inducing stomatal opening. In addition, these effects of D
      tubocurarine and nicotine on stomatal movement can only be found in medium
      containing K(+) while no effects can be found in medium containing Ca(2+), The
      result by Western blotting showed that at least alpha-and beta-subunits of
      nicotinic receptor existed in microsomes of guard cell protoplasts. It was found
      that the distribution of nicotinic acetylcholine receptor was mainly on the
      surface of protoplasts as shown by FITC labelled alpha-bungarotoxin. The results
      above show that nicotinic acetylcholine receptor exists in guard cells and
      mediates acetylcholine to induce stomatal opening.

PMID- 18726223
TI  - Identification of a novel DNA-binding protein to osmotin promoter.
AB  - One novel osmotin promoter, binding-protein (OPBP1) gene, was isolated from salt
      adapted tobacco suspension cells using yeast one-hybrid system. The OPBP1
      interacted specifically in vivo with FA, a DNA sequence from the 5 upstream
      region of osmotin gene, which was essential for osmotin responsiveness. The
      deduced amino acid sequence of OPBP1 contained a conserved motif of a new gene
      family, AP2 family. This protein did not contain the typical motif found in the
      most known DNA-binding proteins and transcription factors.

PMID- 18726224
TI  - FSHB subunit gene is associated with major gene controlling litter size in
      commercial pig breeds.
AB  - An insertion fragment in porcine FSHbeta subunit gene was cloned by PCR.
      Sequencing data show that the insertion is a retroposon of 292 bp sitting in
      intron I at the site between + 809 and +810 base. Based on these results, a PCR
      programme was created to genotype animal individuals in different pig breeds at
      FSW locus and polymorphism of FSHbeta gene was analyzed. With the combination of
      genotype and litter size of sows, it was demonstrated that FSHbeta locus is
      closely associated with major gene controlling litter size in commercial pig
      breeds, such as Yorkshire, Landrace, Durco. Averagely the AA sows give more 1.5
      piglets than BB sows do per litter.

PMID- 18726225
TI  - Breeding technology of alloplasmic wheat.
AB  - Novel wheat bearing alloplasm was bred via nucleo substitution backcross. Through
      comparative study between the hornonucleo-heterocytoplasmic lines and
      homocytoplasm-heteronuclear lines, it was shown that a portion of the alloplasm
      types were able to produce useful genetic effects on wheat yield, grain quality,
      tolerance of salt and resistance to diseases. Among the species studied, the
      cytoplasm of Aegilops crassa, Ae. squarrosa and Ae. vcntricosa contributed the
      best effect. Specific combination of nuclear genes and cytoplasmic genes
      conferred specific characteristics and degree of nucleoplasmic heterosis. The
      alloplasmic wheat lines with cytoplasm substituted were successfully bred with
      good quality and resistance to disease and harsh conditions. In particular, the
      new variety of nucleoplasmic hybrid having Ae. crassa cytoplasm proved the best
      in production test, demonstration and regional test and was consequently pre
      approved for large-scale plantation. The probing of the genetic variations and
      the utilization of alloplasmic wheat was proven to be valuable for both genetic
      study and breeding of new varieties.

PMID- 18726226
TI  - Raman spectroscopic characteristics of microcosmic and photosensitive damage on
      space structure of liposomes sensitized by hypocrellin and its derivatives.
AB  - Raman spect-pic characteristics of microcosmic and photosensitive damage on space
      structure of DP-PC liposomes sensitized by hypocrellin and its derivatives are
      obvious. The trans conformation decreased and the gauche conformation increased.
      The longitudinal order-parameter in chains and the lateral order-parameter
      between chains decreased in different degrees. The lateral packing became loose.
      Photodamage on the liposomes sensitized by 5-Br-hypocrellin B was stronger than
      that by hypocrellins A and B.

PMID- 18726227
TI  - Transient expression of hepatitis B virus surface antigen (HBsAg) and human
      erythropoietin (hEPO) genes in milk after direct introduction into ewe.
AB  - The ability to deliver nonviral DNA directly into animals would provide major
      practical and economic benefits. To pursue this potential, as a preliminary
      approach, the expression in mammary epithelial cells with nonviral DNA ending
      HBsAg and hEPO was investigated by in vivo delivery directly into mammary gland
      Either the bovine asl-casein-HBsAg or the WAE-hEPO gene construct was introduced
      into mammary glands of dm by mammary artery injection. A single injection of
      10(11) copies of DNA construct was implemented for a doe. Transient expression of
      the constructs in milk collected from milk letdown by induction up to 19 d after
      injection was measured with an hEPO ELISA kit from Boehringer Mannheim (Cat. No.
      1 693 417) for rhEPO, and a HBsAg-ELISA kit (Abbott Lab. USA) for rHBsAg. The
      treated animals showed mean concentration of recombinant molecules at 16 microg/L
      for rHBsAg, and 2 mg/L for rhEPO in milk.

PMID- 18726228
TI  - Baculovirus-mediated gene transfer into mammalian cells.
AB  - A kind of cytotoxinic gene barnase was cloned downstream of Immediate early
      promoter from cytomegalovirus (CMV). Recombinant virus vAcCMVBar was constructed
      using Bac-to-Bac system by insertion of the expression cassette into the
      polyhedrin gene locus of Autographa californica nuclear polyhedrosis virus
      (AcNPV). Cytotoxinic effect caused by expression of barnase was observed in four
      mammalian cells after vAcCMVBar infection Dose-dependent analysis revealed that
      one of the cells HICAM was the most sensitive to the virus infection. It was.
      shown that AcNPV could be used as gene transfer vector in mammalian cells and
      that barnase is the suitable report gene which could be detected more easily than
      that commonly used.

PMID- 18726229
TI  - Nuclear matrix of the most primitive eukaryote Archezoa.
AB  - Accumulating evidence suggests that unicellular Archezoa are the most primitive
      eukaryotes and their nuclei are of significance to the study of evolution of the
      eukaryotic nucleus. Nuclear matrix is an ubiquitous important structure of
      eukaryotic nucleus; its evolution is certainly one of the most important parts of
      the evolution of nucleus. To study the evolution of nuclear matrix, nuclear
      matrices of Archezoa are investigated.Giardia lamblia cells are extracted
      sequentially. Both embedment-free section EM and whole mount cell EM of the
      extracted cells show that, like higher eukaryotes, this species has a residual
      nuclear matrix in its nucleus and rich intermediate filaments in its cytoplasm,
      and the two networks connect with each other to form a united network. But its
      nuclear matrix does not have nucleolar matrix and its lamina is not as typical as
      that of higher eukaryotes; Western blotting shows that lamina of Giardia and two
      other Archezoa Entanzoeba invadens and Trichomonas vaginali all contain only one
      polypeptide each which reacts with a mammalia anti-lamin polyclonal serum and is
      similar to lamin B (67 ku) of mammalia in molecular weight. According to the
      results and references, it is suggested that nuclear matrix is an early
      acquisition of the eukaryotic nucleus, and it and the "eukaryotic chromatin" as a
      whole must have originated very early in the process of evolution of eukaryotic
      cell, and their origin should be an important prerequisite of the origin of
      eukaryotic nucleus: in the lamin (gene) family, B-type lamins (gene) should be
      the ancestral type and that A-type lamins (gene) might derive therefrom.

PMID- 18726230
TI  - Changes of characteristics of preoptic neurons and NA metabolism in hypothalamus
      of ground squirrel (Citelleus Dautieus) in different seasons and hibernating
      phases.
AB  - The unit firing activities of neurons in the preoptic area (POA) of ground
      squirrel hypothalamic tissue slices were recorded and the metabolism of NA in
      hypothalamus was measured with high performance liquid chromatography (HPLC).
      Thermosensitivity, proportions, the critical temperature (Tc) and the lowest
      temperature (TL) of firing activity of the above-mentioned neurons, and NA
      metabolism in hypothalamus were compared in different seasons and hibernating
      phases. In comparison with that in summer euthermar, it was shown that (i) the
      percentage and thermosensitivity of the POA neurons varied respectively in the
      hibernating phases; (ii) TL and Tc of the POA neurons in winter, both euthermar
      and hibernation, were markedly decreased; (iii) the POA neurons in hibernation
      became much more sensitive to NA, and the response of cold-sensitive neurons to
      NA changed from inhibiting pattern in summer to exciting one in hibernation; (iv)
      the contents and metabolism of NA in hypothalamus decreased significantly in the
      entering phase and deep hibernation phase, while the metabolism of NA increased
      remarkably in the arousal phase. These changes might explain the regulatory
      mechanism how ground squirrel actively decreases body temperature (Tb) in
      entering into hibernation and quickly recovers body temperature in arousal phase.

PMID- 18726231
TI  - Isolation and properties of an extremely thermophilic xylanolytic bacterium.
AB  - A strain of extremely thermophilic, anaerobic, xylanolytic bacterium was isolated
      from the hot spring in Kangding County, Sichuan Province, and it was gram
      reaction negative, immobile, non-sporeformative with its cells arranged single or
      in pairs, 0.7-1.0 mum wide and 2.0-5.0 mum long. After being cultured at 75
      degrees Celsius for 3 d on xylan agar rolling tube, its colonies were rounded,
      convex, smooth in margin and transparent, and could not produce pigments, but
      could produce carbon dioxide, hydrogen, lactic acid, acetic acid and trace
      ethanol during the fermentation of xylan.

PMID- 18726232
TI  - Relationship between visual learning/memory ability and brain cAMP level in
      Drosophila.
AB  - Using the flight simulator system, the operant conditioned visual flight
      orientation behavior in Drosophila was studied. It was demonstrated that the
      visual learning performance is associated with age; flies learn more reliably at
      3-4 days than at 1-2 days of age; the cAMP level of brain is also increasing with
      age; the brain cAMP content of nonlearner flies of wild type is much higher than
      that of normal flies; the cAMP level of brain increased abnormally after being
      fed with caffeine, and the learning performance decreased. These results imply
      that a moderate range of cAMP level is necessary for the visual learning and
      memory process. Abnormally high or low level of cAMP causes defects of learning
      and memory ability.

PMID- 18726233
TI  - Nuclear reassembly in vitro is independent of nucleosome/chromatin assembly.
AB  - It was shown that nuclear reassembly was induced by small pieces of DNA fragments
      in cell-free extracts of Xenopus. In an attempt to learn the relationship between
      the nuclear reassembly and nucleosome/chromatin assembly, limited amounts of CM
      Cellulose are used to eliminate the capacity of the egg extract S-150 to assemble
      chromatin. while the forming of nucleosomes is checked with DNA supercoiling by
      plasmid DNA pBR322 incubated in the extract, and further analysed by micrococcal
      nuclease digestion. This depleted extract is then used to induce nuclear
      reassembly around demembraned sperms with membrane vesicles. It is found that CM
      Cellulose depletes histones H2A and H2B efficiently and blocks the assembly of
      nucleosomes, the demembraned sperms are yet reconstituted into nuclei in the
      treated S-150, although the chromatin in reassembled nuclei does not produce
      protected DNA fragments when digested with micrococcal nuclease. It suggests that
      in the cell-free system of Xenopus, DNA can be formed into nuclei without
      assembly of nucleosomes or chromatin.

PMID- 18726234
TI  - Synergistic effects of focus ultrasound with different frequency and
      hematoporphyrin on human tumor cells.
AB  - Human hematopoietic cell K(562), human melenoma cell LiBr and human stomach
      cancer cells were exposed to ultrasound (US, 1.75 W/cm(2), 1.4, 2.16 and 2.4
      MHz)in vitro in the presence or absence of hematoporphyrin (Hp, 100 microg/mL).
      The cell damaging effects of treatments were determined by means of the Trypan
      Blue dye exclusion test, MTT test and FDA test. The experimental results showed
      that the same cell line had different sensibilities to the US of different
      frequencies, and different cell line had different damage at the same acoustical
      radiation. The combined treatment with US and Hp enhanced greatly the cell
      damage, and no sensibility of insonation cells to US with Hp was observed. The
      cell damage tests showed that the results of MTT test corresponded well with that
      of Trypan Blue dye test.

PMID- 18726235
TI  - Molecular cloning, sequence analysis and expression studies of a novel GAmyb
      homologous gene, hvmyb.
AB  - Using a known GAmyb gene as the probe, two fully identical clones were isolated
      from a barley aleurone cDNA library. Sequence analysis showed that their 5'
      termini are highly homologous to the 3' termini of GAmyb (97%) and their 3'
      termini share no significant homology with any myb genes. Therefore, the deduced
      protein may hold intact putative GAmyb activation domain but lack the normal DNA
      binding domain. Northern blot reveals that hvmyb expression in barley aleurone
      layers is strongly up-regulated by gibberellin (GA) and down-regulated by
      abscisic acid (APIA). The tissue-and developmental-stage-specificity of hvmyb was
      also found, which was only expressed in barley aleurone cells and dropped to non
      detectable level soon after germination.

PMID- 18726236
TI  - Solution structure of N-terminal segment of hepatitis B virus surface antigen Pre
      S1.
AB  - A synthetic peptide, the N-terminus of hepatitis B virus surface antigen Pre-S1,
      was studied by two-dimensional NMR techniques. A series of(1)H nuclear magnetic
      resonance experiments were used to complete the identification of spin systems
      and sequential assignments of this 28-residue peptide. 157 distance constraints
      and 55 dihedral angle constraints were obtained. 20 structures with the lowest
      target function were selected by the distance geometry program DIANA. Energy
      minimization and the following 100 ps time-averaged restrained molecular dynamics
      (TR-MD) simulation in aqueous solution were performed for each conformer. After
      TRMD simulation, three locally convergent regions corresponding to residues 22
      31, 36-40, 41-46 were found. The averaged pairwise root-mean-square deviation
      (RMSD) of backbone atoms for them were (1.71+/-0.49)A, (0.76 +/-0.31)A, (1.05 +/-
      0.52)A, respectively. Four reverse turns found in these regions, residues 22-25,
      37-40, 41-44 and 43-46, correspond to several important antibody binding sites
      revealed in relevant immunological research.

PMID- 18726237
TI  - RFLP mapping and race specificity of bacterial blight resistance genes (QTLs) in
      rice.
AB  - By using a set of 315 recombinant inbred lines (RILs) from the cross Lemont
      (japonica) x Teqing (indica) and a complete linkage map with 186 well distributed
      RFLP markers and 3 morphological markers, a major gene (Xa4) and 10 QTLs and 9
      pairs of epistasis loci conferring horizontal resistance to three strains of
      Xanthomonas oryxa pv oryza (Xoo) were mapped. The Teqing allele at Xa4 on
      chromosome 11 acts as a dominant resistant gene against pathogen race CR4 and
      CX08, but as an additive QTL with a significantly (47%) reduced effect against
      the virulent strain, CR6. The major gene Xa4 exhibited stronger degree of race
      specificity. Most QTLs showed consistent levels of resistance against all three
      Xoo strains. The results suggest that a high level durable resistance to Xoo may
      be achieved by cumulative effects of multiple QTL.

PMID- 18726238
TI  - Expression of human transforming growth factor beta1 in E. coli (I) : Direct
      expression in cytoplasm.
AB  - PCR technique is used to amplify the mature peptide gene of human transforming
      growth factor pl (hTGFbeta1); the gene is verified by full-length sequence
      analysis. In DHSalpha/pBV220 expression system, hTGFbeta1 attains expression in
      the cytoplasm of E. coli up to 16%. The recombinant protein is proved to be the
      monomer of hTGFbetal by N-terminal amino acids analysis and immunoblotting. After
      refolding of the monomer protein in vitro in glutathione system or CHPAS/DMSO
      system, the dimeric protein accumulates to 30% in the refolding mixture. The
      recombinant protein is purified to homogeneity on silver staining, and is shown
      to have strong biological activity from MTT bioassay on MvlLu cells.

PMID- 18726239
TI  - Electro-acupuncture-mediated gene transfer.
AB  - Gene transfer is one of the key techniques in gene therapy application.
      Unfortunately, it seems that by now, there still exists no approach with
      simplicity, easiness, efficiency and safety. A novel method for gene delivery,
      electro-acupuncture needle-mediated gene transfer which combined the Chinese
      traditional acupuncture with modem gene introduction, was developed. With
      acupuncture needle carrying exogenous gene into muscle after direct electronic
      stimuli, efficient gene delivery was achieved.

PMID- 18726240
TI  - Mental health implications of migration: a review of mental health community
      studies on Russian-speaking immigrants in Israel.
AB  - INTRODUCTION: Since late 1980s, 1,001,726 immigrants arrived in Israel from the
      former Soviet Union (FSU). A review of community studies on the mental health of
      these immigrants is presented. METHOD: Israeli studies from the past two decades
      were reviewed. Presented are findings on the prevalence of psychological distress
      and psychiatric disorders as well as on a number of risk factors among FSU
      immigrants. RESULTS: Higher psychological distress and psychiatric morbidity were
      consistently found among FSU immigrants compared to the Israel-born. Social
      support was identified as a major stress-mitigating factor in migration. Most
      studies reveal the persistence of psychological distress among FSU immigrants
      during the first 5 years following migration, with a risk period around the
      second and third years following migration. DISCUSSION: Findings from Israel
      corroborate some findings on immigrants in other countries but as they are
      limited to a single immigrant population, replication of these studies is
      necessary.

PMID- 18726241
TI  - Measuring observed mental state in acute psychiatric inpatients.
AB  - BACKGROUND: Relationships within acute psychiatric units between patient-level
      experiences and events and fluctuations in mental state have rarely been
      examined. AIM: Data from a multi-centre service evaluation (11 units, 5,546
      admissions) were used to examine mental state patterns and associations with
      clinical characteristics, events and adverse incidents. METHOD: During the 12
      month evaluation period, nursing staff completed shift-level ratings using a new
      rating scale, the observed mental state (OMS) scale, which assessed active
      psychopathology (emotional distress, disinhibition, psychosis, cognitive
      impairment) and withdrawal (45,885 sets of day/afternoon shift ratings). RESULTS:
      The OMS scale performed satisfactorily and is worth considering elsewhere (e.g.,
      active psychopathology: internal consistency, alpha=0.72; short-term stability,
      r=0.72; sensitivity to change, adjusted standardised difference, ASD=0.71).
      Levels of active psychopathology were much higher on shifts in which reportable
      (ASD=1.47) and less serious aggression occurred (ASD=1.44), compared with other
      shifts in which pro re nata medications were also administered (ASD=0.76),
      suggesting that medication usage often followed these events, and possibly that
      agitation and distress levels either rose rapidly or went initially unnoticed on
      these shifts. Although mental state improved steadily across the admission, one
      fifth of the patients with schizophrenia received OMS psychosis ratings in the
      moderate to severe range during the days prior to discharge. CONCLUSIONS:
      Observed mental state ratings were strongly linked with diagnosis and reflected
      key events and incidents. Routine recording using the OMS scale may assist
      clinical decision-making and evaluation in acute psychiatric units.

PMID- 18726242
TI  - Persistent depressive disorders and social stress in people of Pakistani origin
      and white Europeans in UK.
AB  - INTRODUCTION: We compared depression, social stress and treatment in people of
      Pakistani origin and white Europeans living in an UK city. METHOD: In a
      population-based two-phase sample of 1,856 adults we interviewed 651 (77%) of
      eligible participants, using the schedule for clinical assessment in
      neuropsychiatry and life events and difficulties schedule. We identified 216
      people with depressive and 208 with subthreshold disorder; after 6-months we re
      interviewed 398 (94% response). RESULTS: Depressive disorder was more common in
      Pakistani women only (31.1% [24.1-38.0] vs.19.3% [14.1-24.5]) and persisted more
      often in Pakistanis over 50 years of age (90 vs.66%, P = 0.023). New episodes of
      depressive disorder occurred in 17% of participants who had subthreshold disorder
      at baseline in each ethnic group. Persistent depression in the Pakistani group
      was associated with continuing problems of disabling physical illness and close
      relationships. Treatment was limited and not associated with persistent
      depression. CONCLUSIONS: Persistent depressive disorder in older people of
      Pakistani origin is associated with potentially remediable factors.

PMID- 18726244
TI  - Native medicinal plants commercialized in Brazil - priorities for conservation.
AB  - A majority of the native medicinal plants that are commercialized in Brazil are
      harvested from natural populations. In addition to this essentially unrestrained
      collecting, these plants have been heavily impacted by the cutting and the
      fragmentation of forest formations throughout the country. Considering the
      limited availability of natural resources, threats to species diversity, and the
      necessity of conservation efforts in light of the rapid exhaustion of natural
      ecosystems, it is becoming exceedingly important to establish conservation
      priorities. The present work sought to identify the native medicinal plants
      harvested for industrial purposes and to establish conservation priorities for
      the species of highest commercial value. To that end, a survey of Brazilian
      industrial products that use medicinal plants was undertaken in 54 shops in the
      city of Recife (Pernambuco, NE Brazil). The survey noted information concerning
      the commercial name of the product, its plant composition and pharmaceutical
      presentation, therapeutic indications, as well as the laboratory that produced
      it. Only native species were considered. A total of 74 different native species
      used to produce more than 300 types of products were encountered in the present
      survey. Twelve species demonstrated significant versatility (Species which had
      the highest numbers of different therapeutic indications and body systems), and
      58.33% of these plants were trees. Destructive collecting predominates (58.11%),
      greatly affecting taxa collected exclusively from wild populations (86.49%). The
      intensive use of exclusively wild species and the destructive harvesting
      techniques employed in gathering them create serious problems that will threaten
      the availability of these resources to future generations.

PMID- 18726245
TI  - Effect of sampling method on contaminant measurement in pore-water and surface
      water at two uranium operations: can method affect conclusions?
AB  - This paper describes a comparison of two methods of sediment pore-water sampling
      and two methods of surface water sampling that were used in a broader
      investigation of cause(s) of adverse effects on benthic invertebrate communities
      at two Saskatchewan uranium operations (Key Lake and Rabbit Lake). Variables
      measured and compared included pH, ammonia, DOC, and trace metals. The two types
      of sediment pore-water samples that were compared are centrifuged and 0.45-microm
      filtered sediment core samples vs. 0.2-microm dialysis (peeper) samples. The two
      types of surface water samples that were compared are 53-microm filtered Van Dorn
      horizontal beta samples vs. 0.2-microm dialysis (peeper) samples. Results showed
      that 62% of the sediment core pore water values were higher than the
      corresponding peeper pore-water measurements, and that 63% of the Van Dorn
      surface water measurements were lower than corresponding peeper surface water
      measurements. Furthermore, only 24% and 14% of surface water and pore-water
      measurements, respectively, fell within +/-10% range of one another; 73% and 50%,
      respectively, fell within +/-50%. Although somewhat confounded by differences in
      filtering method, the observed differences are believed to primarily be related
      to small, vertical differences in the environment sampled. Despite observed
      differences in concentrations of toxicologically relevant variables generated by
      the different sampling methods, the weight of evidence (WOE) conclusions drawn
      from each set of exposure data on the possible cause(s) of in situ toxicity to
      Hyalella azteca from a related study were the same at each uranium operation.
      However, this concurrence was largely due to other dominant lines of evidence.
      The WOE conclusions at Key Lake were dominated by the toxicity response of H.
      azteca in relation to exposure chemistry, where as the WOE conclusions at Rabbit
      Lake were informed by exposure chemistry, the toxicological response of H.
      azteca, and whole-body contaminant concentrations in the test organisms. Had
      these multiple lines of evidence not been available, differences in exposure
      chemistry generated by the different sampling methods could have substantially
      influenced the identification of potential causes of in situ toxicity.

PMID- 18726243
TI  - Cardiovascular protection for all individuals at high risk: evidence-based best
      practice.
AB  - Patients with cardiovascular risk factors are largely undertreated, for many
      reasons. Vulnerable individuals may not be aware of the risks they are facing or
      an individual's risk of cardiovascular disease may be underestimated,
      particularly among those at high risk. Furthermore, in individuals identified as
      being at high total cardiovascular risk, the full spectrum of therapeutic options
      may not be implemented or patients may not adhere to the treatment prescribed. We
      address these critical issues by summarizing the existing guidelines: our
      ultimate goal is to encourage the optimal management of individuals at high total
      cardiovascular risk according to evidence-based medicine, with the expectation
      that this will improve outcomes.

PMID- 18726246
TI  - Reproductive biology of freshwater fishes from the Venezuelan floodplains.
AB  - This review describes the endocrine changes that occur during the annual
      reproductive cycle of Pygocentrus cariba, Pimelodus blochii, and Oxydoras
      sifontesi and their relationships with the environmental characteristics of
      Venezuelan floodplains. Most reproductive studies of teleosts have focused on
      changes that occur during annual cycles in temperate species but, in tropical
      fish, this has been examined less frequently. P. cariba, P. blochii, and O.
      sifontesi are seasonal breeders widely distributed along the Orinoco River. Under
      natural conditions they have an annual gonadal cycle closely related to changes
      in the annual hydrology cycle of the Orinoco River which defines two seasons on
      the floodplain: inundation and isolation. The reproductive cycle of these species
      seems to be controlled by cues from the external environment. Relevant data about
      gonadal maturation, for example gonadosomatic index and sexual hormones
      secretion, are contrasted. The role of catecholamines in neuroendocrine control
      of the reproductive axis is also considered in this work.

PMID- 18726247
TI  - A comparison of the humoral and cell-mediated response of pigs experimentally
      infected with either influenza or PRRS viruses.

PMID- 18726248
TI  - Chinese tomato yelIow Ieaf curl virus- a new species of geminivirus.
AB  - Chine tomato yellow leaf curl virus (TYLCV-CHI) and other geminiviruses were
      analysed with 20 monoclonaI antibodies. It was shown that TYLCV-CHI is
      serclogicaIly close to Chinese tabacco Ieaf curl virus (TbLCV-CHI). The fragment
      of TYLCV-CHI DNA including the common region (CR), N-terminal of coat protein
      gene and AV1 gene was amplified by PCR and cloned, and its DNA sequence was
      determined. These raults showed that TYLCV-CHI is different from other known
      geminiviruses in the world, and is a new whitefly-transmitted gerninivirus.

PMID- 18726249
TI  - Molecular mechanism of diapause in insect (I) : Expression of diapause hormone
      gene and incubation temperature in embryonic stage ofBombyx mori.
AB  - The embryonic diapause of the silkworn,Bombyx mori, is induced by the diapause
      hormone (DH) which is secreted from the suboesophageal ganglion of pupae. The
      diapause nature of bivoltine strains uses environmental stimuli as the initial
      signal to determine the diapause nature. The experiments showed that DH gene
      expreon is a direct response to the environmend stimulus, such as high incubation
      temperature. The cDNA from the embryonic stage wa cloned and sequenm analysis
      showed the cDNA encoding DH. Expmion patterns of the DH gene in embryonic stage
      are different ar incubation temperatures 15 degrees C and 25 degrees C,
      suggesting that the incubation tempcreturt as an environmental signal is kept
      within the body to control the DH gene expmion at the pupal stage, so that the
      embryonic diapause of next generation can be determined.

PMID- 18726250
TI  - Differential effects of ca(2+) and Mg (2+) on endonuclease activation in isolated
      promyelocytic HL-60 cell nuclei.
AB  - In autodigestion assays, endonucleaw activity in non-apoptotic HL-60 promydocytic
      leukemia cell nuclei cleaved the chromatin of he autologous cells to an
      oligonucleosomal length pattern. Both EGTA and EDTA inhibited the activation of
      endonuclease activity in isolated HL-60 cell nuclei. The inhibition by EDTA could
      be reversed by exogenous Ca(2+). but not by exogenous Mg(2+). In Ca(2+)/Mg(2+)
      free nuclei digation buffer, addition of Ca(2-->) (1-10 mmol/L) induced
      endonuclease activity in the isolated nuclei, while addition of Mg(2+) had no
      effect. In the presence of Ca(2+)(0.1 mmol/L), endonuclease activity was enhanced
      by exogenous Mg(2+) (0.1-10mmol/L). These results suggest that the endonuclease
      responsible for internucleosomal DNA fragmentation in HL-60 cells during
      apoptosis is activated by Ca(2+) and further modulated by Mg(2+) in the presence
      of ca(2+).

PMID- 18726251
TI  - Raman spectroscopic study of DNA after photosensitive damage caused by
      hypocrellins A and B.
AB  - Laser Raman spectroscopy provided the direct evidence for microcosmic photodamage
      in space structure of DNA molecule. When photosensitive damage was made to space
      structure of calf thymus DNA by hypocrellins A and B. the Raman characteristic
      frequencies and the intensities of the bands assigned to various groups of the
      components of DNA (phosphate backbone dsoxyribose and four bases) changed at
      various degrees. There were not only the strsnd breakage, but also the breakage
      of some H-bonds and disruption of vertical base-base stacking interactions. The
      photosensitive damage of hypocrellin B on DNA was stronger than that of
      hypocrellin A on DNA.

PMID- 18726252
TI  - Variation of wheatgrass chromosomes in wheat-wheatgrass alien addition line "TAI
      27" revealed by fluorescencein situ hybridization (FISH).
AB  - The Karyotyp of the primary wheat-whastgrass alien addition line TAI-27 was 2n =
      44 in which all d the chromosomes were metacentric and subrmetacentric. However,
      in the progeny of TAI-27 a pair of chromosomes had become small chromosomea in
      the two morphologically different plants. Fluorescence in situ hybridizstionm
      (FISH) technique was used to analyze the two different plants. The observations
      indicate that a pair of small chromosomes in one varietion line are from
      wheatgrass. In another variation line, a pair of small chromosomes are also from
      whest-grass, while another pair of wheatgrass chromosomes have substituted the
      wheat chromosomes. TAI-27 and its variant lines showed a high level of resistance
      to barley yellow dwarf virus (BYDV). The pessible explanation for such a
      variation and the potential use of the variant lines were discussed briefly.

PMID- 18726253
TI  - Isolation and characterization of five rice telomere-associated sequences.
AB  - Acoording to the telomere-repeated sequences of rice, two primers: (TTTAGGG11)(3)
      and (CCC-TAA.A)(3)CCC were used to amplify rice telomere-assciated sequences
      (TASs). Fox PCR template preparation. total DNA was digested with restrictive
      endonuclease and then ligated. Using the ligates or total DNA sa template, eight
      fragments were obtained with the single primer by the PCR reaction. To confirm
      that the sequences are derived from telomeric DNA, we conducted Bal31 digestion
      analysis. Of the eight fragments, seven were susceptible to Bal31 treatment,
      suggesting that they were TASs. These DNA fragments were further demonstrated u,
      be rice sub-telomeric sequences by RFLP mapping Five sequences have been mapped
      to the distal ends on rice chromme 5,6,7 and 9, and two other sequences have been
      mapped at interstitial sites, suggesting that (TTTAGGG)(n). also exist in the
      middle of rice chromosomes-All eight fragments were sequenced and characterized.

PMID- 18726254
TI  - Influence of loop sequence on relative stability of bimolecular triplex DNA.
AB  - The structures of 20 bimolecular triplexes have been built and simuleted by
      molecular mechanics. The sequence of pyrimidine strand is 5'-dTTCTTTC-L(1) TTTI
      (3)CTTTTcTT-3, where the five nucleotides underlined cornpaw Ioop sequences. L(1)
      and L(5) represent varied residues. The sequences of purine strands are 5'
      dGAAAAGAA-3' and the reversed orientation 5'-dAAGAAAG-3'. The influence of
      different loop sequences and compositicm on the relative stability of twenty
      triplexes have bem energetically analyzed. The results indicate that 5'-loop
      triplexes are more stable than 3'-loop ones and the stacking interaction of
      purines with their adjacent basw are stronger than that of pyrimidines. The
      stability of triplexes is mainly determined by the first and last nucleotides in
      the loop.

PMID- 18726255
TI  - Production and characterization of a human single-chain Fv to collagenase IV.
AB  - The over-expression of collagenase IV in tumor tissues was found to be closely
      related to tumor metastasis. Collagenase IV has been therefore considered as one
      of the novel indicative molecules for tumor diagnosis and treatment. Based on
      phage display antibody library technique, a single-chain Fv specific for
      colbgenase IV was successfully cloned. This antibody, referred to as hCo4, was
      mainly composed of variable regions from heavy and liiht chains, with its
      molecular weight of 27 ku. The engineered antibody bound to collagenase IV
      specifically. The affinity of hCo4 was found to be the same as that of a single
      chain antibody constructed from a monoclonal antibody to collagenase IV. Since
      hCo4 is the smallest among all the antibodies specific for collagenase IV and it
      is of human origin, it has a potential to be applied for tumor irnmunotherapy and
      for the study of the relationship between collagenase IV and tumor metastasis.

PMID- 18726256
TI  - Somatic cell cryopreservation and protoplast regeneration of important disease
      resistant wild riceOryza meyeriana Baill.
AB  - Oryza meyeriana Baill is one of the three wild rice species found in Chiia.O.
      mcyeriana possesses valuable characteristics but is reluctant in cell culturein
      vitro. In a series of experiments, callus with no regeneration ability was
      induced from young panicle ofO. meyeriana. The callus was subcultured and
      propagated. Embryogenic cell clones were obtained after cryopreswation.
      Suspension cultures were established and protoplasts were isolated and
      regenerated into plants. Results of artificial inoculation ofXanthomonas
      campestris pv.Oryzae showed that the strong resistance did not change in the
      regenerated plants. The development of protoplast-to-plant system is an important
      progress towards utilization ofO. meyeriana via cellular engineering. The
      experiments demonstrated that cryopreservation of plant calli was a new way to
      obtain embryogenic cell line.

PMID- 18726257
TI  - Synthesis and blood compatibility of rutile-type titanium oxide coated LTI
      carbon.
AB  - Titanium oxide films were synthesized by ion beam enhanced deposition, where the
      films were prepared by depositing titanium atoms and simultaneously bombarding
      with Xe(+) ions at an energy of 40 keV in an O(2) environment. The titanium oxide
      films exhibit rutile-type structure with (100) orientation and the O/Ti ratio is
      about 2:1. Ti(2+), Ti(3+) and Ti(4+) coexist in the films.In vitro andin vivo
      investigations were used to investigate the blood compatibility of titanium oxide
      films. The results show that the blood compatibility of rutile-type titanium
      oxide fi is better than that of low temperature isotropic pyrolytic carbon (LTI
      carbon), which is widely used to fabricate artificial heart valve. It is thought
      that rutile-type titanium oxide coated LTI-carbon most probably becomes new
      biomaterial to fabricate artificial heart valves.

PMID- 18726258
TI  - Expression and regulation of hFIX minigene and cDNA driven by beta-casein gene in
      mouse mammary gland.
AB  - Mammary gland specific expression vectors for human clotting factor IX (hFIX) and
      LacZ reporter gene driven by bovine beta-casein gene were constructed. Vectors
      were packaged by stearylamine (SA) liposome and were transferred to lactating
      mice via tail vein. Both hFIX and Lac2 gene could be expressed in the mammary
      gland of the treated mice. The highest production of hFIX protein was 80.28 ng
      per mL milk, and more than 85% of hFIX protein appeared to be gamma-carboxylation
      and biologically active. The results suggested that the 2.0 kb sequence of beta
      casein gene including promoter, exon 1 was effective to drive hFIX gene
      expression in mammary gland and intron 1 of beta-casein gene had an effect on the
      tissue specific expression. The expression level in mouse milk injected with hFIX
      minigene vector containing hFIX endogenous intron 1 was increased by above 3
      times of that injected with hFIX cDNA vector.

PMID- 18726259
TI  - Crystal structure of pokeweed antiviral protein from seeds ofPhytolacca americana
      at 0.25 nm.
AB  - Crystals of pokeweed antiviral protein (PAP) from seeds ofPhytolacca americana
      with high diffraction ability were grown from high protein concentration (100
      mg/mL) solution at high temperature (33 degrees C). The crystal structure was
      solved by use of molecular replacement method and refied by use of molecular
      dynamic method at 0.25 nm to anR factor of 18.15% with standard deviations from
      standard geometry of 0.001 6 nm and 2.04 for bond lengths and bond angles,
      respectively. Comparison with two other PAPS revealed, near the active center, a
      sequence- and structure-variable region, consisting of the loop connecting the
      fifth beta-strand with the second alpha-helix and including a proposed active
      residue, suggesting this loop probably to be related to difference in activity.

PMID- 18726260
TI  - Correlation between expression of cadherin and gap junctional communication in
      human lung carcinoma cells.
AB  - The correlation between expression of ca(2+)-dependent cell adhesion molecule,
      cadherin, and gap junctional intercellular communication (GJIC) in human lung
      carcinoma PG cell line and connexin43 (Cx43) cDNA transfected PG cell clones was
      investigated. Results from immunoblotting and immunofluorescent staining revealed
      that cultured normal human lung cells (RF) expressed N-cadherin. However, the
      expression level of Kcadherin in PG cells was very low in comparison with normal
      RF cells. The Cx43 transfected PG clones exhibited comparable levels of Cx43
      protein, but varied in the level of N-cadherin expression and in the function of
      GJIC as measured by scrape-loading and dye transfer (SLDT) method. Positive
      correlation between N-cadherin and GJIC was demonstrated. Thein vitro andin uivo,
      growth examination results suggest that N-cadherin mediated cell-cell adhesions
      and Cx43 functional expression, the GJIC, may work coordinately with each other
      in regulation of cell growth and differentiation. Deficiency in both GJIC and
      cell adhesion may be crucial for cell transformation.

PMID- 18726261
TI  - Construction of a fusion protein between N-terminal 153 peptide of thrombopoietin
      and erythropoietin.
AB  - Thrombopoietin (TPO) functions as a regulator of megakaryocytes in their
      differentiation and maturation, and is a candidate pharmaceutical for the curing
      of thrombocytopenia. Erythropoietin (EPO) is a hematopoietic cytokine that
      regulates the level of red blood cell. It is widely used in renal anemia and
      tumor associated anemia, and is proved to be safe and effective. In order to
      study the possibility of using TPO-EPO fusion protein for the curing of anemia
      and thrombocytopenia induced by high dose chemotherapy, a fusion gene is
      constructed by linking TPO N-terminal 153 peptideand EPO mature peptide-coding
      region. The fusion gene is expressed in mammalian cells, revealing that the
      expression product can support the growth of TPO responsive Ba/F3-mpl cells and
      EPO dependent Bet-2 cells in the absence of any other stimulating cytokine. It
      also stimulates the formation of erythroid colonies and megakaryocytic colonies
      in semi-solid bone marrow cultures. These results indicate that the fusion
      protein has both thein vitro activities of TPO and EPO. The preliminaryin vivo
      experiment reveals that the TPO-EPO fusion protein containing cell supernatant
      raises the platelet level by 37 % in mice, while its function on erythroid
      hematopoiesis remains to be determined. These results indicate that the
      construction of TPO-EPO fusion protein and the further study of its use in high
      dose chemotherapy are possible.

PMID- 18726262
TI  - Effect of adeno-associated virus-mediated transfer of low density lipoprotein
      receptor gene on treatment of hypercholesterolemia.
AB  - Low density lipoprotein receptor (LDL-R) plays an important role in removing LDL
      from plasma and preventing prbducing atherosclerosis. To test hepatic
      reconstitution of LDLR expression is sufficient for metabolic correction of
      subjects with hypercholesterolemia; a recombinant adeno-associated virus (rAAV)
      carrying the human LDL receptor cDNA (AAV/LDL-R) was constructed. Using
      adenosome, a complex of ademviral capsid protein and lipsome, to transfer the
      rAAV into livers of rabbits with experimental hypercholesterolemia could elicit
      the production of LDL-R and lower plasma cholesterol level. These results
      demonstrate that AAV-mediated transfer of LDL-R gene may provide an alternative
      means to gene therapy of hypercholesterolemia.

PMID- 18726263
TI  - Statistical recovering of incomplete genotypic information of DNA molecular
      markers.
AB  - Genetic information provided by a dominant marker about the genotype is partial
      or incomplete, and a missing marker provides no information at all. In the
      present study, based on some basic genetic and statistical principles, a general
      algorithm is proposed to systematically recover the genotypic information of all
      dominant and missing markers on a genome for individuals from an F(2) population.
      The recovered information can then increase the efficiency and precision in
      mapping quantitative trait loci (QTL) and marker assisted selection (MAS). The
      derived method can be easily extended to other populations consisting of all 3
      genotypes on each marker locus, such as populations derived from an F(2) by
      selfing or random mating.

PMID- 18726264
TI  - Spatiotemporal organization of simple-cell receptive fields in area 18 of cat's
      cortex.
AB  - Spatiotemporal structures of receptive-fields (RF) have been studied for simple
      cells in area 18 of eat by measuring the temporal transfer function (TTF) over
      different locations (subregions) within the RF. The temporal characteristics of
      different subregions differed from each other in the absolute phase shift (APS)
      to visual stimuli. Two types of relationships can be seen: (i)The APS varied
      continuously from one subregion to the next: (ii) A 180 degrees -phase jump was
      seen as the stimulus position changed somewhere within the receptive field.
      Spatiotemporal receptive field profiles have been determined by applying reverse
      Fourier analysis to responses in the frequency domain. For the continuous type,
      spatial and temporal characteristics cannot be dissociated (space time
      inseparable) and the spatiotemporal structure is oriented. On the contrary, the
      spatial and temporal characteristics for the jumping type can be dissociated
      (space-time separable) and the structure is not oriented in the space-time plane.
      Based on the APSs measured at different subregions, the optimal direction of
      motion and optimal spatial frequency of neurons can be predicted.

PMID- 18726265
TI  - Isolation, properties and spatial site analysis of gamma subunits of B
      phycoerythrin and R-phycoerythrin.
AB  - Polysiphonia urceolata R-phycoerythrin and Porphyridium cruentum B-phycoerythrin
      were degraded with proteinaseK, and then the nearly native gamma subunits were
      isolated from the reaction mixture. The process of degradation of phycoerythrin
      with proteinaseK showed that the gamma subunit is located in the central cavity
      of (alphabeta)(6) hexamer of phycoerythrin. Comparative analysis of the spectra
      of the native phycoerythrin, the phycoerythrin at pH 12 and the isolated gamma
      subunit showed that the absorption peaks of phycoerythrobilins on alpha or beta
      subunit are at 535 nm (or 545 nm) and 565 nm, the fluorescence emission maximum
      at 580 nm; the absorption peak of phycoerythrobilins on the isolated gamma
      subunit is at 589 nm, the fluorescence emission peak at 620 nm which overlaps the
      absorption maximum of C-phycocyanin and perhaps contributes to the energy
      transfer with high efficiency between phycoerythrin and phycocyanin in
      phycobilisome; the absorption maximum of phycourobilin on the isolated gamma
      subunit is at 498 nm, which is the same as that in native phycoerythrin, and the
      fluorescence emission maximum at 575 nm.

PMID- 18726266
TI  - A novel strategy for construction of immuno-PCR gene probe and its preliminary
      application in diagnosis.
AB  - An alpha-fetoprotein (AFP) antibody gene probe was constructed using chlorophyll
      molecule as a coupler between protein and dsDNA. The preliminary study on the
      detection of AFP using this novel probe was performed by immuno-PCR. and the
      results indicated that the sensitivity of the gene probe by immuno-PCR is 10(4)
      10(5) times higher compared with ELI SA. The construction of immuno-PCR gene
      probe in this way not only completely prevents the protein from contacting with
      organic solvent and maintains the native conformation of the proteins, but also
      anchors protein to dsDNA in a fixed orientation and makes PCR amplification more
      efficient. The gene probe thus constructed is stable for at least 6 months at
      room temperature. This new approach is exquisite, simple, less expensive, and
      suitable to a variety of applications.

PMID- 18726267
TI  - Crystal structure of R22L trichosanthin.
AB  - Crystals of R22L TCS were grown by vapour diffusion method. X-ray diffraction
      data were collected to 0.191 nm resolution on a Siemens X-200B area detector. The
      XENGEN programme was applied to data processing; the data were used to 0.22 nm.
      The structure was determined by the difference Fourier method and refined using X
      PLOR programme. The final R factor was 0.182. The rms deviation of bond length
      and bond angle were 0.0013 nm and 2.770 degrees respectively. In R22L TCS, two
      water molecules occupy the space left by Arg changed to Leu. The side chain of
      Gin168 rotates abut 50 degrees . The OE2 atom of Glu168 links to the NZ atom of
      Lya165 through water molecule. The new hydrogen bond net partially replaces the
      Arg22 function. The effect of the conservative hydrogen bonds between secondary
      structures on the conformation of active pocket was discussed.

PMID- 18726268
TI  - Mechanism of regulating the expression of lambdaN gene by ribosomal protein at
      translational level.
AB  - In ribosomal protein S12 mutant or L24 mutant the expression of lambdaN gene was
      depressed at translational level. To study its mechanism the lambdaN gene region
      of lambdaN -lacZ gene fusion was trimmed from its 5' end to 3' end with DNA
      exonuclease III (DNA exoIII) in order to alter the TIR (translational initiation
      region) and the coding region of lambdaN gene. After DNA sequencing 23 species of
      different lambdaN-lacZ fused genes were obtained. The beta-galactosidase
      activities of these deletants in ribosomal protein mutant were compared with that
      in wild type strain. The result indicated that (i) S12 mutant could affect 305
      subunit's binding to the TIR of lambdaN gene messenger and cause the difficulty
      in forming 30s initiation complex and then decrease the efficiency of
      translational initiation; (ii) in S12 mutant the coding region of lambdaN gene
      also affected the expression lambdaN gene; (iii) in L24 mutant the inhibition of
      lambdaN gene expression was not related to translational initiation and the 5'
      end of the coding region of lambdaN gene, but related to the 3' end of lambdaN
      gene.

PMID- 18726269
TI  - Purification and properties of glutamate synthase from Streptomyces lincolnensis.
AB  - Glulamale synthase (EC 1.4.1. 14) was purified to homogeneity from 8 cell-free
      extract of Streptomyces lincolnensis by precipitation with streptomycin sulfate
      and ammonium sulfate, and column chromatography on DEAE cellulose, Sepharose 6B,
      DEAE-sephadex A-50, hydroxyapatite and Sephadex G-150. The enzyme activity is
      stabilized by addition of alpha-ketoglutarate, PMSF, EDTA, beta-mercaptoethanol
      and glycerol. The native enzyme has a molecular weight of 138 000 and is composed
      of two nonidentical subunits with molecular weights of 81 000 and 57 000.
      Spectroscopic examination of the enzyme gave absorption maximum at 280 and none
      at 380 and 440 nm, indicating the absence of iron and flavin. The enzyme shows
      optimum activity at pH 7.2 and 30 degrees C. Km values for alpha-ketoglutarate, L
      glutamine and NADH were 417, 435, and 52.1 micromol/L, respectively. When NADPH
      was substituted lor NADH as reductant, there was approximately 13% of the control
      activity. The activity of this glutamate synthase is inhibited by its products
      (i.e. glutamate and NAD), several metal ions, amino acids and tricarboxylic acid
      cycle intermediates.

PMID- 18726270
TI  - Expression of structural proteins of hepatitis C virus (HCV) in mammalian cells.
AB  - The vaccinia viral vector containing T7 promoter was used to construct the
      expression plasmids carrying HCV structural genes of C, El and E2/NS1. These
      genes were transiently expressed in mammalian cells in the presence of the T7 RNA
      polymerase which was provided by the recombinant vaccinia virus vTT7. Expression
      of mature core protein, envelope protein El and E2 was detected by Western blot
      using HCV patient sera as the primary antibodies. It was found that the sera from
      different HCV patients reacted differently with the expressed products, so did
      the sera collected at different times from the same patient, from whom the HCV
      structural genes were isolated. Among six mammalian cell lines, Vero and HeLa
      were the most suitable for the expression of C, El and E2-The recombinant
      vaccinia viruses have been constructed to constantly produce the C, El and E2
      proteins for further research.

PMID- 18726271
TI  - A modified hepatitis B surface antigen carrying both preS1 and preS2 epitopes.
AB  - The DNA fragments coding for preS2(120-146) and preS1(21-47) amplified by PCR
      were fused to both 5' and 3' ends of S gene at the position of amino acid 223.
      The fusion gene was placed downstream of the promoter P7.5 of the universal
      vaccinia viral vector pGJP-5 and the recombinant vaccinia virus vS2SSI was then
      selected by invivo homogeneous recombination. Fusion protein S2SS1 could be
      expressed in the mammalian cells infected with vS2SSl. The investigation of
      expression, secretion, antigenicity and particle assembly of the S2SS1 protein
      demonstrated that S2SS1 protein could be assembled into particles which presented
      preSl, preS2 and S antigenicity and be efficiently secreted from the cells. It
      also showed that the level of its expression and secretion approached to that of
      the S protein expressed by the recombinant vaccinia virus.

PMID- 18726272
TI  - Effects of calmodulin and calmodulin binding protein BP-10 on phosphorylation of
      thylakoid membrane protein.
AB  - Light-induced phosphorylation of endogenous thylakoid membrane protein can be
      inhibited markedly by a novel inhibitor CaMBP-10 which is discovered and isolated
      from plant. The inhibitory effect of BP-10 can be eliminated by addition of CaM.
      At the same time, the phosphorylation can also be inhibited by EGTA or CaM
      antagonists, such as TFP (trifluoperazine) and W-7 (N-(6-aminohexyl)-5-chloro-l
      naphthalene sulfonamide). This result implies that (i) Ca(2+) and CaM most likely
      participate in and regulate plant photosynthesis; (ii) the kinase that catalyzes
      thylakoid membrane protein phosphorylation can be regulated by Ca(2+) and CaM.
      However, the further experiments indicate that BP-10 has no effect on
      dephosphorylation of thylakoid phosphoproteins.

PMID- 18726273
TI  - Fine structure and assembly in vitro of nuclear lamina in plant cells.
AB  - The fine structure of the nuclear lamina (NL) in sperm cells of Ginkgo biloba was
      visualised using high resolution low-voltage scanning electron microscopy
      (LVSEM). It was shown that the nuclear lamina was composed of 10 nm filaments
      which formed a fine network. Lamins were purified from cultured carrot suspension
      cells and assembled in vitro. Long 8-12 nm diameter filaments were seen and
      sometimes subfilaments could be distinguished. Western blot of filament
      preparations showed that these contained the 66 and 84 ku lamins. These data
      demonstrate that plant lamins are capable of assembling into filaments in vitro.

PMID- 18726274
TI  - A novel liver-directed gene delivery system using an autonomously replicating
      vector specifically expressed in AFP positive hepatoma cells.
AB  - A composite EBV-based expression vector, pEBAF, was constructed with the 5'
      flanking sequence of human alpha-fetoprotein gene as a promoter. Complexed to
      galactosylated histone, this vector with a foreign DNA insertion could be
      transferred into hepatic cells via the asialoglycoprotein receptor mediated
      endocytosis pathway. It was replicated as an episome, and its expression was
      restricted to the AFP positive hepatoma cells. This new gene delivery method has
      the following advantages: (i) absence of a potential toxicity is related to viral
      vectors; (ii) the targeting is specific to AFP positive hepatoma cells; (iii) the
      introduction of the EBV replicon into this system results in the high level
      expression and long-term maintenance of the transferred gene. This novel gene
      delivery system has potential applications in gene therapy for the treatment of
      hepatocellular carcinoma.

PMID- 18726275
TI  - In vitro enhancing effects of thymic dendritic cells on apoptotic cell death of
      thymocytes.
AB  - Using terminal deoxynucleotide transferase-mediated dUTP-digoxigenin nick end
      labeling (TUNEL) assay and propidium iodide-DNA staining flow cytometry assay,
      the effects of mouse thymic dendritic cells (MTSC4) on the process of programmed
      cell death of thymocytes in vitro were investigated. It was noticed that
      thymocytes bound to MTSC4 used in this study. That the percentages of apoptotic
      nuclei of the bound thymocytes on MTSC4 were much higher than those of medium
      cultured thymocytes, while the bound thymocytes on mouse thymic epithelial cell
      (MTEC1) showed much lower percentages of apoptosis. FACS analysis quantitatively
      confirmed the observation. Phenotype analysis showed that MTSC4 induced the
      deletion of CD4 + CD8 + cells and CD4 + CD8-.cells in 18 h of coculture. The
      results suggest that the negative selection of medullary thymocytes may be
      achieved by thymic dendritic cells through their enhancing effects on apoptosis.

PMID- 18726276
TI  - Attenuation of seizure in P77PMC rats with an HSV-vector expressing IL-1ra in
      brain.
AB  - Cloned human IL-1ra (IL-1 receptor antagonist, IL-1ra) cDNA is inserted into
      pHSVLac, resulting in recombinant named pHSV-IL-1ra. pHSVLac and pHSV-IL-lra were
      packaged into HSV-1 particles using HSV-1 ts K as helper virus. The results
      showed that: (i) vero cell infected by pHSV-IL-1ra particles showed IL-1ra
      expression; expression of beta-galactosidase is observed in meninges and some
      neurons closed to ventricular and maintained for 8 weeks in rats after
      intracerebroventricular injection of pHSV-IL-1ra particles; (ii) transgenic
      expression of IL-lra by pHSVIL-lra injection significantly inhibited seizure
      attacks of P77PMC rat. These studies indicate that HSV-1 vector expressing IL-1ra
      in brain attenuated seizure attacks of P77PMC rat.

PMID- 18726277
TI  - Construction of antisense RNA expression vectors and correction of splicing
      defect in human beta-globin gene (IVS-2-654 C-->T mutant) in HeLa cells.
AB  - The antisense fragments, which were available in in vitro system, were cloned
      into the mammalian expression vector pcDNA3, and were transfected into H654
      cells, a mammalian cell line stably expressing the thalassaemic (IVS-2-654 C-->T)
      human beta-globin gene. In these transfected cells, the level of correctly
      spliced beta-globin mRNA in total beta-globin mRNA (beta/(beta + beta*)) was
      improved from 0.07 (0 d) to 0.22 (3 d), and this effect persisted for up to 15 d
      post transfection. All the results demonstrated that antisense RNAs were able to
      be transcribed from the antisense fragment expression vectors stably and
      effectively suppressed aberrant splicing pattern of the mutated beta-globin gene
      (IVS-2-654 C-->T) and restored correct splicing pathway. This work provided a
      novel approach with potential clinical significance to gene therapy of this kind
      of splicing mutants including beta-thalassaemia (IVS-2-654 C-->T) by antisense
      RNAs.

PMID- 18726278
TI  - Therapeutic effects on experimental metastatic tumor-bearing mice by vaccination
      with GM-CSF gene-modified and tumor antigen-pulsed macrophages.
AB  - Macrophages, with potent cytotoxic and antigen-presenting activities, can be used
      in cancer treatment. The biological characteristics and antitumor effect of GM
      CSF gene-modified and tumor antigen-pulsed macrophages were investigated. The
      high levels of GM-CSF could be detected in the supernatants of macrophages after
      gene transfer. The cytotoxicity and the expression of MHC class II molecules of
      the gene-modified macrophages increased significantly and the antigen-presenting
      ability was enhanced. The gene-modified macrophages were then pulsed with tumor
      antigen and used to treat the experimental pulmonary metastastic mice. The number
      of pulmonary metastases was reduced significantly and the cytotoxicity of the CTL
      induced from the splenocytes of the tumor-bearing mice also increased. The
      results demonstrated that adenovirus-mediated GM-CSF gene transfer can activate
      macrophages to some extent and GM-CSF gene-modified, antigen-pulsed macrophages
      may be a new type of effective effector cells in the immunogene therapy of
      cancer.

PMID- 18726279
TI  - Preparation and characterization of monoclonal antibodies against adenylate
      kinase.
AB  - Six hybridoma cell lines that can continuously secrete monoclonal antibodies
      against adenylate kinase (AK) have been produced. The characteristics including
      the subclass and molecular weight of monoclonal antibodies manufactured by these
      strains are also determined. Further studies show that the two monoclonal
      antibodies McAb3D3 and McAb4D8 bind easily with AK absorbed on microtitration
      plates, with affinity constants of 8.4 x 10(8) M(-1) and 9.6 x 10(8) M(-1), while
      their interactions to AK in solution are much weaker, with affinity constants of
      7.0 x 10(4) M(-1) and 3.9x10(6) M(-1), respectively. Thus, McAb3D3 and McAb4D8
      react preferentially to the immobilized AKs. Since proteins are often partially
      denatured when absorbed on microtitration plates, it is suggested that both
      McAb3D3 and McAb4D8 are directed against non-native AK.

PMID- 18726280
TI  - Biological function of modified nucleotides T(54) and Psi(55) of yeast tRNA(Ala).
AB  - The 3' half molecule of yeast tRNA(Ala) (nucleotides 36-75) was hybridized with a
      DNA fragment (5'GGAATCGAACC 3') and the hybrid was then digested with E. coli
      RNase H (from Boehringer). The enzyme can specifically cleave the 3' half
      molecule at the 3' side of nucleotide Psi(55), thus a fragment C(36)-Psi(55) was
      prepared. The 3'-terminal T or TPsi of this fragment was removed by one or two
      cycles of periodate oxidation and beta-elimination. The products were fragments
      C(36)-T(54) and C(36)-G(53). Three yeast tRNA(Ala) fragments C(56)-A(76), U(55)
      A(76) (with Psi(55) replaced by U), U(54)-A(76) (with T(54)Psi(55) replaced by
      UU) were synthesized and ligated with three prepared fragments (C(36)-Psi(55),
      C(36)-T(54) and C(36)-G(53)) respectively by T4 RNA ligase. The products were
      further ligated with the 5' half molecule (nucleotides 1-35). Using this method,
      one reconstituted yeast tRNA(Ala) (tRNAr) and two yeast tRNA(ALa) analogs: (i)
      tRNAa with U(55) instead of Psi(55); (ii) tRNAb with U(54)U(55) instead of
      T(54)Psi(55) were synthesized. The charging and incorporation activities of these
      three tRNAs were determined. In comparison with the reconstituted tRNA, the
      charging activity was 75% for tRNAa and 45% for tRNAb and the incorporation
      activity was 65% for tRNAa and 70% for tRNAb. These results suggest that the
      modified nucleotides T(54) and Psi(55) play an important role in yeast tRNA(Ala)
      function.

PMID- 18726281
TI  - Relation between nuclear envelope and nuclear lamina in nuclear assembly in
      vitro.
AB  - Xenopus laevis egg extracts cell-free nuclear assembly system was used as an
      experimental model to study the process of nuclear lamina assembly in nuclear
      reconstitution in vitro. The experimental results showed that lamin was involved
      in the nuclear assembly in vitro. The assembly of nuclear lamina was preceded by
      the assembly of nuclear matrix, and probably, inner nuclear matrix assembly
      provided the basis for nuclear lamina assembly. Inhibition of normal assembly of
      nuclear lamina, by preincubating egg extracts cell-free system with anti-lamin
      antibodies, resulted in abnormal assembly of nuclear envelope, suggesting that
      nuclear envelope assembly is closely associated with nuclear lamina assembly.

PMID- 18726282
TI  - Immunomodulated signaling in macrophages: Studies on activation of Raf-1, MAPK,
      cPLA(2) and secretion of IL-12.
AB  - Little is known about the mechanism and signal transduction by LPS-mediated
      immunomodulation of murine peritoneal macrophages. It is found that the signal
      molecules of the down-stream of Ras, Raf-1, MAPK p44, and MAPK p42 are
      phosphorylated, and cPLA(2) is activated with a significant increase of the
      release of [ H(3) ] AA by macrophages in response to LPS and PMA. Compared with
      the very recent finding that LPS and PMA trigger the activation and translocation
      of PKC-alpha and PKC-epsilon, these findings suggest that there is a connection
      between PKC signaling pathway and the Raf-1/MAPK pathway and that the activation
      of these main signaling events may be closely related to the secretion of IL-12
      during LPS-induced modulation of macrophages.

PMID- 18726283
TI  - Four types of potassium currents in motor nerve terminals of snake.
AB  - The experiments were performed on transversus abdominis muscle of Elaphe dione by
      subendothelial recording. The results indicate that in snake motor nerve endings
      there exist four types of K(+) channels, i.e. voltage-dependent fast and slow
      K(+) channels, Ca(2+)-activated K(+) channel and ATP-sensitive K(+) channel. (i)
      The typical wave form of snake terminal current was the double-peaked negativity
      in standard solution. The first peak was attributed to Na(+) influx (I(Na)) in
      nodes of Ranvier. The second one was blocked by 3,4-aminopyridine (3,4-DAP) or
      tetraethylammonium (TEA), which corresponded to fast K(+) outward current
      (I(k.f)) through the fast K(+) channels in terminal part. (ii) After I(K.F) as
      well as the slow K(+) current (I(K.S)) were blocked by 3, 4-DAP, the TEA
      sensitive Ca(2 +)-dependent K(+) current (I(K(Ca))) passing through Ca(2 +)
      activated K(+) channel was revealed, whose amplitude depended on [K(+)](o) and
      [ca(2+) ](o). It was blocked by Ba(2+), Cd(2+) or Co(2+). (iii) I(K.F) and
      I(K(Ca)) were blocked by TEA, while I(K. S) was retained. It was sensitive to 3,4
      DAP, partially blocked by ethanol (200 mmol/L) or beta-bungarotoxin (2
      micromol/L), and enhanced by low pH (6.4-6.7). This is the first report that
      certain current component of motor nerve terminal is sensitive to pH in the range
      of 6. 4-7. 5. (iv) That diazoxide (200 micromol/L) increased the second negative
      peak and the effect was eliminated after further addition of glibenclamide (50
      micromol/L) was taken as evidence for the presence of ATP-sensitive K(+) current
      (I(K.ATP)) at snake nerve terminal.

PMID- 18726284
TI  - Mismatch negativity of ERP in cross-modal attention.
AB  - Event-related potentials were measured in 12 healthy youth subjects aged 19-22
      using the paradigm "cross-modal and delayed response" which is able to improve
      unattended purity and to avoid the effect of task target on the deviant
      components of ERP. The experiment included two conditions: (i) Attend visual
      modality, ignore auditory modality; (ii) attend auditory modality, ignore visual
      modality. The stimuli under the two conditions were the same. The difference wave
      was obtained by subtracting ERPs of the standard stimuli from that of the deviant
      stimuli. The present results showed that mismatch negativity (MMN), N2b and P3
      components can be produced in the auditory and visual modalities under attention
      condition. However, only MMN was observed in the two modalities under inattention
      condition. Auditory and visual MMN have some features in common: their largest
      MMN wave peaks were distributed respectively over their primary sensory
      projection areas of the scalp under attention condition, but over fronto-central
      scalp under inattention condition. There was no significant difference between
      the amplitudes of visual and auditory MMN. Their amplitudes and the scalp
      distribution were unaffected by attention, thus suggesting that MMN amplitude is
      an important index reflecting automatic processing in the brain. However, the
      latency of the auditory and visual MMN were affected by attention, showing that
      MMN not only reflects automatic processing but also probably relates to control
      processing.

PMID- 18726285
TI  - Genetic distances between Chinese populations calculated on gene frequencies of
      38 loci.
AB  - Genetic distances were calculated for Han subpopulations in different provinces,
      cities and autonomous regions and ethnic minorities in China by using gene
      frequency data of 38 loci, and genetic trees were constructed. The results showed
      that, among both Han and ethnic minorities, there were two types, i.e. southern
      and northern Mongoloids, with Yangtze River as boundary. Therefore, both African
      origin theory and local origin theory about the modern man should answer the
      question: when did these two types separate and how did they develop. This paper
      also conclusively proved genetically that the Han subpopulations in different
      regions are genetically close to the local ethnic minorities, which indicates
      that much blood of ethnic minorities has mixed into Han, at the same time, some
      blood of Han also has mixed into the local ethnic minorities.

PMID- 18726286
TI  - Effect of lysophosphatidylcholine on behavior and structure of
      phosphatidylcholine liposomes.
AB  - Differential scanning calorimetry (DSC), fluorescence polarization and X-ray
      diffraction were performed to investigate the kinetics of the micellar to the
      lamellar phase transition of dipalmitoylphosphatidylcholine/1
      palmitoylphosphatidylcholine (16:0 LPC/DPPC) liposomes at gel phase. With a 16:0
      LPC concentration up to 27 mol% only the sharp main transition with relatively
      high enthalpy (DeltaH) values of DPPC was observed. Increasing 16 : 0 LPC
      concentration, the phase transition was broadened and the transition enthalpy was
      decreased and finally totally disappeared. The fluorescence probes of 3AS, 9AS,
      12AS, and 16AP were employed, respectively, to detect the mobility of various
      sites of carbon chains of DPPC or 16:0 LPC/DPPC liposomes. It was shown that DPPC
      liposomes formed in the absence of 16:0 LPC always had a fluidity gradient in
      both gel and liquid-crystalline phase, while in the presence of 14.1 mol% and
      27.0 mol% 16:0 LPC in the mixtures, the fluidity gradient tended to disappear
      below 40 degrees C. In the case of 27.0 mol% 16:0 LPC in the 16:0 LPC/DPPC
      mixtures the polarization of the sixteenth carbon of acyl chains was similar to
      that of the sixth at 10 degrees C. Small-angle X-ray diffraction showed that when
      increasing 16:0 LPC concentration there was a significant decrease in the 16:0
      LPC/DPPC liposome thickness. Thickness of the lipid layer of DPPC was 7.30 nm,
      but those of the samples containing 14.1 mol% and 27.0 mol% of 16:0 LPC were
      reduced to 6.79 and 5.52 nm at 25 degrees C, respectively. Wide-angle X-ray
      diffraction showed that a reflection appeared at 0.42 nm with a broad shoulder
      around 0.41 nm in pure DPPC at a lipid concentration of 300 mg/mL at 25 degrees
      C. In the 16:0 LPC/DPPC system, a single sharp reflection appeared at 0.41 nm. It
      can be concluded that DPPC forms an interdigitated gel phase in the presence of
      16:0 LPC concentration below 30 mol%, above this concentration micellization of
      the bilayers occurs. The interdigitated structures were destabilized slowly with
      16:0 LPC concentration increasing, and finally the 16:0 LPC/DPPC bilayers fit
      into the micelles with its concentration up to 60 mol%.

PMID- 18726287
TI  - A new baculovirus of cultured shrimps.
AB  - By means of ultrathin section, negative staining and sucrose gradient ultra
      centrifugation, a new baculovirus has been discovered and purified in lymphoid
      organs and such tissues as muscles of the shrimps which have been spontaneously
      attacked by diseases and artificially infected. With a diameter of 96-112 nm,
      this is the thickest baculovirus of shrimps ever known. In the center is the high
      density nucleus. Between the capsid and the envelope is a broad space, which is
      not found in any of the baculoviruses of the prawns ever reported. On the surface
      of the purified nucleocapsid, there is a subunit of the spiral arrangement, which
      is also characteristic of this virus. It has not been observed and found in the
      epithelial cells of the livers, intestines and cheeks, which is quite different
      from the fact that prawn baculoviruses infect a certain epithepilial cell of the
      above-mentioned ones without exception. The viruses only multiplicate inside the
      core of target cells, which will not form occluded bodies or inclusion bodies. It
      is a new virus which has never been reported. It is called lymphoid cell nuclear
      baculovirus (LNBV).

PMID- 18726288
TI  - A ketoreductase gene from Streptomyces mycarofaciens 1748 DNA involved in
      biosynthesis of a spore pigment.
AB  - An efficient plasmid transformation system for S. mycarofaciens 1748 has been
      established. In order to determine the function of MKR gene in S. mycarofaciens
      1748, the gene disruption experiment was carried out. For this purpose the
      plasmid pKC1139 was used. A recombinant strain with white spore appeared, in
      contrast to the grey-colour spore of S. mycarofaciens 1748. This suggested that
      homologous recombination between plasmid-borne MKR gene sequence and the
      chromosome of S. mycarofaciens 1748 had occurred. A Southern hybridization
      experiment using a-(32)P-labelled MKR gene as probe indicated that the desired
      integration event had occurred in the recombinant. The result of gene disruption
      showed that the alteration of this gene in the chromosome of S. mycarofaciens
      1748 made sporulating colonies remain white instead of taking on the typical grey
      colour of sporulating wild type colonies, suggesting that MKR gene is involved in
      the biosynthesis of a spore pigment. The recombinant strain was incubated with
      fermentation medium optimised for midecamycin production. A TLC assay showed that
      the recombinant strain produced midecamycin in quantities comparable to that of
      S. mycarofaciens 1748. A pCN8B12 was a clone from genomic library of midecamycin
      producing strain which contained a 28-kb DNA insert. The 28-kb DNA fragment
      contained act I-homologous and act III-homologous regions. he PKS (act I
      homologous) and MKR (act III-homologous) genes that define spore pigment of
      midecamycin producing strain were localized by restriction endonuclease digestion
      with pCN8B12, indicating that they are separated by about 10 kb DNA. The
      polyketide synthase gene cluster of similar organization has not been reported
      yet.

PMID- 18726289
TI  - Human augmenter of liver regeneration: Molecular cloning, biological activity and
      roles in liver regeneration.
AB  - The complete amino acid sequence of human augmenter of liver regeneration (hALR)
      was reported by deduction from nucleotide sequence of its complementary DNA. The
      cDNA for hALR was isolated by screening a human fetal liver cDNA library and the
      sequencing of this insert revealed an open reading frame encoding a protein with
      125aa and highly homologous (87%) with rat ALR encoding sequence. The recombinant
      hALR expressed from its cDNA in transient expression experiments in cos-7 cells
      could stimulate DNA synthesis of HTC hepatoma cell in the dose-dependent and heat
      resistant way. Northern blot analysis with rat ALR cDNA as probe confirmed that
      ALR mRNA was expressed in the normal rat liver at low level and that dramatically
      increased in the regenerating liver after partial hepatectomied rat. This size of
      hALR mRNA is 1.4 kb long and expressed in human fetal liver, kidney and testis.
      These findings indicated that liver itself may be the resource of ALR and
      suggested that ALR seems to be an important paracrined regulator of liver
      regeneration.

PMID- 18726290
TI  - Molecular characterization of suppression of hepatitis B virus transcription by
      hepatitis C virus core protein.
AB  - To further elucidate the molecular mechanisms underlying the suppression of
      hepatitis B virus (HBV) expression by the hepatitis C virus (HCV) core protein,
      five molecular clones of HCV cDNA sequence containing the 5' noncoding (5'NC) and
      the core regions have been isolated from Chinese HBV- and HCV-coinfected
      patients. Sequence comparison and phylogenetic analysis showed that the HCV
      sequence cloned from coinfected individuals is indistinguishable from that
      identified in other patients. Cotransfection assay confirmed that the core
      protein expressed from one of the cloned sequence is capable of suppressing the
      expression of hepatitis B surface and e antigens (HBsAg and HBeAg, respectively).
      Deletion mapping revealed that the C-terminal hydrophobic region of the HCV. core
      is necessary for the suppression. Results from reporter assays demonstrated that
      HCV core protein interacts with the HBV C promoter and enhancer II elements and
      down-regulates the transcription of HBV as well as other cellular and
      heterologous viral genes in both hepatic and non-hepatic cell lines. Taken
      together, the findings suggest HCV core protein as a multifunctional negative
      regulator of transcription critically involved in the molecular interactions
      between HBV and HCV, and between HCV and the cell.

PMID- 18726291
TI  - Characterization of progenies of Triticum aestivum-Psathyrostachys juncea
      derivatives by using genomic in-situ hybridization.
AB  - Using genomic in-situ hybridization (GISH) technique, 7 translocation-addition
      lines, 6 translocation and translocation-addition lines, 2 ditelosomic addition
      lines and 1 translocation line were identified from Triticum aestivum L. 
      Psathyrostachys juncea (Fisch.) Nevski intergeneric hybrids, of which
      translocation-addition and translocation and translocation-addition lines were
      not found in other reports. No substitutions and disomic additions were detected
      in the, hybrids and breakages occurred in all P. juncea chromosomes studied.
      Results have shown that the improved GISH technique is a rapid and economical
      method for use in this field.

PMID- 18726292
TI  - Exon structure requirements for yeast tRNA ligase.
AB  - Different nucleotides were introduced into nucleotides 32, 37 and 38 of yeast
      tRNA(Phe) precursors via oligonucleotide directed mutations. Pre-tRNAs were
      prepared using T7-transcription in vitro and spliced with the purified yeast tRNA
      endonuclease and tRNA ligase. It is demonstrated that tRNA ligase activities will
      be inhibited by the 5'-double-stranded end of 3'-halves.

PMID- 18726293
TI  - Prediction of mutant activity and its application in molecular design of tumor
      necrosis factor-alpha.
AB  - Two models for prediction of the activity and stability of site-directed
      mutagenesis on tumor necrosis factor-alpha are established. The models are based
      on straightforward structural considerations, which do not require the
      elaboration of sitedirected mutagenesis on the protein core and the hydrophobic
      surface area by analyzing the pmperties of the mutated amino acid residues. The
      reliabilities of the models have been tested by analyzing the mutants of tumor
      necrosis factor-alpha (TNF-alpha) whose two leucine residues (L29, L157) were
      mutated. Based on these models, a TNFalpha mutant with high activity was created
      by molecular design.

PMID- 18726294
TI  - Double-gating mechanism and diversity of an adenosine triphosphate (ATP)
      sensitive K(+) channel in neurons acutely dissociated from rat neocortex.
AB  - Classically, ion channels are classified into 2 groups: chemical-sensitive
      (ligand-gated) and voltage sensitive channels. Single ATP-sensitive K(+) (K-ATP)
      channel currents were recorded in acutely dissociated rat neocortical neurons
      using patch clamp technique. A type of K-ATP channel has been found to be gated
      not only by intracellular ATP, but also by membrane potential (V(m)), and proved
      to be a novel mechanism underlying the gating of ion channels, namely bi-gating
      mechanism. The results also show that the K-ATP channels possess heterogeneity
      and diversity. These types of K-ATP channels have been identified in 40.12% of
      all patches, which are different in activation-threshold and voltage-sensitivity.
      The present experiment studied the type-3 K-ATP channel with a unitary
      conductance of about 80 pS in detail (n = 15). Taking account of all the
      available data, a variety of K-ATP channels are suggested to exist in body, and
      one type of them is bi-gated by both chemical substances and membrane potentials.
      This property of the K-ATP channels may be related to their pathophysiological
      function.

PMID- 18726295
TI  - Construction of a recombinant human GM-CSF/MCAF fusion protein and study on itsin
      vitro andin vivo antitumor effects.
AB  - A novel cytokine fusion protein was constructed by fusing granulocyte macrophage
      colony stimulating factor (GM-CSF) with monocyte chemotactic activating factor
      (MCAF), which acts as a factor directing effector cells (monocytes) to a target
      site. The recombinant human GM-CSF/MCAF fusion protein could sustain the growth
      of GMCSF-dependent cell line TF1 and was chemotactic for monocytes. Thein vitro
      antitumor effect showed that rhGM-CSF/MCAF could activate monocytes to inhibit
      the growth of several human tumor cell lines, including a promyelocyte leukemia
      cell line HL-60, a lung adenocarcinoma cell line A549, a hepatoma cell line SMMC
      7721 and a melanoma cell line Bowes. Furthermore, the cytotoxicity of monocytes
      activated by rhGM-CSF/MCAF against HL-60 and A549 was greater than that activated
      by GM-CSF or MCAF alone, even greater than that activated by a combination of GM
      CSF and MCAF, suggesting that the fusion protein has synergistic or enhanced
      effects. Thein vivo antitumor effect indicated that rhGM-CSF/MCAF had marked
      antitumor effect against A549 tumor in nude mice and even completely suppressed
      tumor formation. rhGM-CSF/MCAF was significantly more effective in inhibiting
      tumor growth than rhGM-CSF. Histological analysis showed that tumor site injected
      with rhGM-CSF/MCAF was infiltrated by a large number of monocytes while a sparse
      infiltration of monocytes was observed at the tumor site injected with rhGM-CSF
      or normal saline, suggesting that the antitumor effect of rhGM-CSF/MCAF was
      mediated by the recruitment of a large number of monocytes to the tumor site.

PMID- 18726296
TI  - Molecular fluctuation in living cells.
AB  - The concept of molecular fluctuation in living cells is introduced. Many
      apparently different experimental facts in living cells, including the velocity
      non-uniformity of organelle movement, the saltatory movement of transport
      vesicles in axoplasmic transport, the chromosome oscillation during metaphase in
      mitosis and the pauses in the chromosome movement during anaphase are explained
      using a unified viewpoint. A method of determination of average number of the
      attached motor protein molecules from the experimental data is also proposed.

PMID- 18726297
TI  - In vitro flowering ofDendrobium candidum.
AB  - Dendrobium candidum, a wild orchid species from China, normally requires three to
      four years of cultivation before it can produce flowers. The effects of plant
      hormones and polyamines on flower initiation of this species in tissue culture
      were investigated. The addition of spermidine, or BA, or the combination of NAA
      and BA to the culture medium can induce protocorms or shoots to flower within
      three to six months with a frequency of 31.6%-45.8%. The flowering frequency can
      be further increased to 82.8 % on the average by pre-treatment of protocorms in
      an ABA-containing medium followed by transfer onto MS medium with BA. The
      induction of precocious flowering depends on the developmental stage of the
      experimental materials (protocorms, shoots and plantlets) used, and usually
      occurs only when mt formation is inhibited.

PMID- 18726298
TI  - Spontaneous and light-induced photon emission from intact brains of chick
      embryos.
AB  - Photon emission (PE) and light-induced photon emission(LPE) of intact brains
      isolated from chick embryos have been measured by using the single photon
      counting device. Experimental results showed that the intensity level of photon
      emission was detected to be higher from intact brain than from the medium in
      which the brain was immerged during measuring, and the emission intensity was
      related to the developmental stages, the healthy situation of the measured
      embryos, and the freshness of isolated brains as well. After white light
      illumination, a short-life delayed emission from intact brains was observed, and
      its relaxation behavior followed a hyperbolic rather than an exponential law.
      According to the hypothesis of biophoton emission originating from a delocalized
      coherent electromagnetic field and Frohlich' s idea of coherent long-range
      interactions in biological systems, discussions were made on the significance of
      photon emission in studying cell communication, biological regulation, living
      system's relevance to its environment, and also on the relations between the
      detected photon emission and the coherent electromagnetic field. The detected
      photon emission should be comprehended in the manner of the interactions between
      the intrinsic fields within the living systems and their environmental external
      fields.

PMID- 18726299
TI  - Construction of a trivalent candidateShigella vaccine strain with host-vector
      balanced-lethal system.
AB  - A trivalent liveShigella vaccine candidate FSD01 against S.flexneri 2a, S.sonnei
      and S.dysenteriae I was constructed. This candidate strain was based on the
      S.flexneri 2a vaccine T32. By homologous recombination exchange, the
      chromosomalasd gene of T32 was site-specifically inactivated, resulting in the
      strain unable to grow normally in LB broth, while anotherasd gene of S.mutans was
      employed to construct an Asd(+) complementary vector. This combination ofasd (-)
      host/Asd(+) vector formed a balanced-lethal expression system in T32 strain. By
      use of this system, two important protective antigen genes coding for S.sonnei
      Form I antigen and Shiga toxin B subunit were cloned and expressed in T32, which
      led to the construction of trivalent candidate vaccine FSD01. Experimental
      results showed that this strain was genetically stable, but its recombinant
      plasmid was non-resistant. Moreover, it was able to effectively express trivalent
      antigens in one host and induce protective responses in mice against the
      challenges of the above threeShigella strains.

PMID- 18726300
TI  - Ultrastructure and function of follicle cell in the ovary ofBranchiostoma
      belcheri.
AB  - The ultrastructure of follicle cells in the ovary at different developmental
      stages ofBranchiostoma has been observed in detail with a transmission electron
      microscope. The results indicate that only one kind of follicle cell exists with
      structural features related to steroid hormone biosynthesis: (i) oval or round
      mitochondria with tubules; (ii) smooth surfaced endoplasmic reticulum; (iii)
      several large lipid droplets in the cytoplasm; (iv) a well developed Golgi
      complex and tubular rough surfaced endoplasmic reticulum, as can be found in
      mammalian theca interna cells. In addition, as steroid hormone synthesizing
      cells, they obviously play an important role in the phagocytosis of relict
      gametes and cellular debris and may have a nutritive function for the oocytes.
      They can produce abundant secretory granules in stages III-IV ovaries. In mature
      ovaries they transform into flat epithelial cells with numerous microfilaments
      which may play a role in ovulation.

PMID- 18726301
TI  - Differential effects of nitric oxide on rod and cone pathways in carp retina.
AB  - The effects of nitric oxide (NO) on electroretinograms and light responses of
      horizontal cells intracellularly recorded from isolated, superfused carp retinas
      were studied. Sodium nitroprusside (SNP), an NO donor, suppressed scotopic b
      wave, while enhancing photopic b wave, and the effects could be blocked by
      hemoglobin, an NO chelator. Furthermore, following SNP application, light
      responses of rod horizontal cells were reduced in size and those of cone
      horizontal cells were increased. These results suggest that NO suppresses the
      activity of rod pathway, but enhances that of cone pathway in the outer retina.
      Moreover, the effects of methylene blue, an inhibitor of soluble guanylate
      cyclase, on rod and cone horizontal cells were just opposite to those of SNP,
      implying that the effects of NO may be mediated by cGMP.

PMID- 18726302
TI  - A model for visual image-background discrimination by relative movement.
AB  - Biologically plausible electronic neural network setup for real time processing
      motion image information was built. Using this setup the first part of the model
      was examined and real time discrimination of moving object image was realized
      from complex background in high resolution. Afterimages may play an important
      role in filtering moving object image and the aperture problem should be
      separated into two parts: the first part, i.e. the incomplete filtered moving
      object image, can be better resolved by parallel integration of multi-channel
      visual information, however, the second part, i.e. the inaccurate measurement
      results for movement direction, may only get certain compensation by visual
      integration.

PMID- 18726303
TI  - A multilayer neural network model for perception of rotational motion.
AB  - A multilayer neural nerwork model for the perception of rotational motion has
      been developed using Reichardt's motion detector array of correlation type,
      Kohonen's self-organized feature map and Schuster-Wagner's oscillating neural
      network. It is shown that the unsupervised learning could make the neurons on the
      second layer of the network tend to be self-organized in a form resembling
      columnar organization of selective directions in area MT of the primate's visual
      cortex. The output layer can interpret rotation information and give the
      directions and velocities of rotational motion. The computer simulation results
      are in agreement with some psychophysical observations of rotational perception.
      It is demonstrated that the temporal correlation between the oscillating neurons
      would be powerful for solving the "binding problem" of shear components of
      rotational motion.

PMID- 18726304
TI  - Increasing drug resistance in human lung cancer cells by mutant-type p53 gene
      mediated by retrovirus.
AB  - Human mutant-type (mt) p53 cDNA was synthesized and cloned from human lung cancer
      cell line GL containing mt-p53 gene by using polymerase chain reaction (PCR). It
      was confirmed that the mt-p53 cDNA contained the complete coding sequence of p53
      gene but mutated at codon 245 (G-->T) and resulted in glycine to cysteine by
      sequencing analysis. The retroviral vector pD53M of the mt-p53 was constructed
      and introduced into the drug-sensitive human lung cancer cells GAO in which p53
      gene did not mutate. The transfected GAO cells strongly expressed mutant-type p53
      protein by immunohistochemistry, showing that pD53M vector could steadily express
      in GAO cells. The drug resistance to several anticancer agents of GAO cells
      infected by pD53M increased in varying degrees, with the highest increase of 4
      fold,in vitro andin vivo. By quantitative PCR and flow cytometry (FCM) analyses,
      the expression of MDR1 gene and the activity of P-glycoprotein (Pgp) did not
      increase, the expression of MRP gene and the activity of multidrug resistance
      related protein (Mrp) increased slightly. These results indicated that the drug
      resistance associated with mt-p53 gene might be somewhat correlated with MRP/Mrp
      but not with MDR1/Pgp. It was possible to modify the tumor drug resistance by
      changing status of p53 gene.

PMID- 18726305
TI  - Sequence analysis of lacZ(-) mutations induced by ion beam irradiation in double
      stranded M13mp18DNA.
AB  - While M13mp18 double-stranded DNA was irradiated with ion beam, and transfected
      intoE. coli JM103, a decrease of transfecting activity was discovered. The lacZ(
      ) mutation frequency at 20% survival could reach (3.6-16.8) x 10(4), about 2, 3
      10 times that of unirradiated M13DNA. Altogether, 27 IacZ(-)mutants were
      selected, 10 of which were used for sequencing. 7 of the sequenced mutants show
      base changes in 250-bp region examined (the remaining 3 mutants probably have
      base changes outside the regions sequenced). 5 of the base-changed mutants
      contain more than one mutational base sites (some of them even have 5-6
      mutational base sites in 250-bp region examined); this dense distribution of base
      changes in polysites has seldom been seen in X-rays, Y-rays or UV induced DNA
      mutations. Our experiments also showed that the types of base changes include
      transitions(50%), transversions (45%) and deletion (5%); no addition or
      duplication was observed. The transitions were mainly C-->T and A-->G; the
      transversions were mainly C-->A and C-->G. The mutations involving cytosine
      residue (in the template strand) constitute about 60% of all the base changes
      observed. In comparison with the surrounding sequences of mutational base sites,
      the base located between TG and CT is found to be easily substituted.

PMID- 18726306
TI  - Alterations of cardiac and lymphocyte beta- adrenoceptors in rat with chronic
      heart failure.
AB  - The alterations of cardiac and lymphocyte beta-adrenoceptors were observed in the
      rats with chronic heart failure produced by constriction of both abdominal aorta
      and renal artery. The results showed that beta(1)-adrenoceptor density and mRNA
      levels were increased, whereas these levels remained unchanged for beta(2). The
      concentrationcontractile response curve for isoproterenol was shifted m the right
      in cardiac atrium, whereas the concentration-CAMP accumulation response curve for
      isoproterenol in myocardium was not changed. The number of beta-adrenoceptom in
      blood lymphocyte was markedly reduced. Thus in the heart-failure rats the density
      of cardiac beta-adrenoceptor was increased accompanying reduced beta
      adrenoceptormediated positive inotropic response, suggesting a post adenylate
      cyclase dysfunction or impaired contractile components. In contrast, the
      alteration of beta-adrenoceptor in lymphocyte is consistent with the reduced beta
      adrenoceptor-mediated inotropic response in heart.

PMID- 18726307
TI  - Selective reversal of drug resistance in drug-resistant lung adenocarcinoma cells
      by tumor-specific expression of mdrl ribozyme gene mediated by retrovirus.
AB  - According to the fact that CEA gene expressed only in lung adenocarcinoma and not
      in normal lung cells, a retroviral vector (pCEAMR) was constructed which carried
      the CEA promoter coupled to MDRl ribozyme gene. pCEAMR was introduced into drug
      resistant lung adenocarcinoma cells GAOK with CEA expression and HeLaK without
      CEA expression; the expression of pCEAMR and drug resistance in the infected
      cells were analyzedin vitro andin vivo; pCEAMR expressed only in CEA-producing
      GAOK cells and not in non-CEA-producing HeLa cells. The drug resistance to
      doxorubicin (DOX) decreased 91.5% in the infected GAOK cells and did not change
      in the infected HeLa cells. In nude mice, DOX could obviously inhibit the growth
      of the infected GAOK tumors, and had no effect on the growth of the infected HeLa
      cells. These results indicated that MDRl ribozyme gene regulated by CEA promoter
      expressed only in human adenocarcinoma cells and reversed their drug resistance
      selectively. This gene-drug therapy might serve as an effective treatment method
      for patients with CEA-producing lung cancers which was usually refractory to
      conventional chemotherapy.

PMID- 18726308
TI  - Selective suppression of rod signal transmission by cobalt ions of low levels in
      carp retina.
AB  - Selective suppression of rod signal transmission by cobalt ions was reported in
      carp retina. Using 10 munol/L Co(2+), rod-driven horizontal cells were
      hyperpolarized and light responses were completely suppressed in superfused,
      isolated retina, while cone-driven horizontal cells were almost unaffected.
      Similarly, scotopic electroretinographic bwave was suppressed by 10 munol/L
      Co(2+), while the photopic b-wave remained unaffected. Furthermore, the glutamate
      isolated receptor potential (PIII) was not altered by low Co(2+) under dark
      adapted conditions. Other divalent ions with high affinity to calcium channels,
      such as cadmium and manganese ions, did not show similar suppressive effect on
      the rod horizontal cells. When rod horizontal cells were hyperpolarized by 10
      munol/L Co(2+), the use of 3 mmol/L glutamate caused a significant depolarization
      of the cells, indicating that Co(2+) application did not impair the ability of
      these cells to respond to glutamate. On the other hand, application of 200
      munol/L beta-hydroxyaspartate, a glutamate transport blocker, mimicked the effect
      of low Co(2+), suggesting a possibility that the low Co(2+) effect might be
      related to a blockade of glutamate uptake by rods.

PMID- 18726309
TI  - Phylogeny of 12 species of genusGlycine Willd. reconstructed with internal
      transcribed region in nuclear ribosomal DNA.
AB  - The ITS-Is of 24 accessions belong to 10 species of subgenusGlycine, and 2
      species of subgenusSoja of genusGlycine were amplified, cloned and sequenced.
      According to the homology of the sequences, the phylogeny of the 24 accessions
      were reconstructed. The reconstructed dendrogram showed that there were some
      divergent genomic types found in the previously classified species, such asG.
      tomentella, G. canescens andG. tabacina, and they might be some cryptic species
      by morphologic analysis.

PMID- 18726310
TI  - Genetic diversity analysis by RAPD inCathaya argyrophylla Chun et Kuang.
AB  - Genetic diversity level ofCathaya argyrophylla was confirmed by random amplified
      polymorphic DNA (RAPD) markers. Seventy five samples (individuals), collected
      from Hunan and Sichuan provinces of China were used in the study. 21 10-mer
      oligonucleotide primers detected 106 sites, and 34 (32%) of them were
      polymorphic. The level of genetic variation in C.argyrophylla was lower than
      those of other conifers, and was considered to be associated with the complexity
      of habitats. The percentages of polymorphic sites (PPS) in the Hunan and Sichuan
      populations were 18% and 25% respectively. 7.99% of genetic variation existed
      between the two populations; this value was higher than the mean value (6.8%)
      among populations in conifers displayed by allozyme. Some subpopulations ofC.
      argyrophylla were greatly differentiated because of site mutation and genetic
      drift. The highest value of genetic difference between subpopulations amounted to
      16. 23%. In addition, a concept of diversity coefficient (DC), a value used to
      measure the genetic diversity level, and its calculation were proposed. The low
      genetic diversity level ofC. argyrophylla was thought to be one of the factors
      causing its endangered status.

PMID- 18726311
TI  - Subzonal fertilization of mouse round spermatids.
AB  - Mouse round spermatids were electrofused with homologous mature oocytes to
      examine the behaviour of their nuclei within the ooplasm and the abilities of
      development. A single spermatid was injected in the perivitelline space of a
      mature oocyte and an electron fusion pulse was given. The best round spermatid
      oocyte pairs (RS-O) fusion took place at 20-30 s AC (1 MHz, 50V/cm) followed by a
      single fusion DC pulse (3 700-3 800 V/cm, 25 mus) and another 30 s AC current.
      The total survival rate and fusion rate of RS-O were 89.0% (575/646) and 61.9 %
      (356/575), respectively. 49.2 % (175/356) of fused oocytes developed to 2PN
      stage. The concentration of Ca(2+) in the fusion medium produced no significant
      effect on the above targets. The 2PN development rate of the fused RS-O from the
      oocytes collected 14-16 h after hCG injection was higher than others. 32.6%
      (57/175) of the 2PN oocytes had fully developed spermatid (male) and oocyte
      (female) pronuclei. The rest spermatid-derived pronuclei remained small in size
      throughout the pronuclear stage. 192 fertilized eggs were transferred surgically
      into the oviducts of the pseudopregnant female mouse. 12 offspring were produced.

PMID- 18726312
TI  - 126Gln is the residue of human IL-2 binding to IL-2R gamma subunit.
AB  - The 126Gln of human interleukin-2 (IL-2) is a conserved amino acid residue. After
      substitution of 126Gln with Asp, the binding abilities of this mutant to
      different composites of IL-2 receptor (R) subunits have been determined. Results
      show that 126AspIL-2 has higher affinity to IL-2R alpha beta gamma complex and
      normal affinity to IL-2R alpha beta complex, but loses its binding ability to IL
      2R beta gamma complex, demonstrating that the 126Gln is the residue of human IL-2
      which binds to IL-2R gamma subunit.

PMID- 18726313
TI  - Mechanism of enhancement of prochymosin renaturation by solubilization of
      inclusion bodies at alkaline pH.
AB  - The renaturation efficiency of recombinant prochymosin depends on not only the
      renaturation conditions but also the solubilization (denaturation) conditions.
      Compared with pH 8, solubilization of prochymosin-containing inclusion bodies at
      pH 11 (8 mol/L urea) results in onefold increase of renaturation efficiency (
      approximately 40% vs. approximately 20 %). Alkaline pH facilitates the
      solubilization of inclusion bodies via the breakage of intermolecular disulfide
      bonds. Moreover, alkaline pH renders prochymosin molecules to be in a more
      reduced and more unfolded state which undergoes refolding readily.

PMID- 18726314
TI  - Influences of cerebellar interpositus nucleus and fastigial nucleus on neuronal
      activity of lateral hypothalamic area.
AB  - Stimulation of cerebellar interpositus nucleus and fastigial nucleus could
      influence the neuronal activity of lateral hypothalamic area in the cat, and some
      of the neurons which respond to the cerebellar stimulations are glucose-sensitive
      neurons. These results suggest that the cerebellum is involved not only in motor
      control, but also in the regulation of non-somatic functions through the
      cerebello-hypothalamic pathways.

PMID- 18726315
TI  - Selection of substrate recognition sequence of protein kinase with ferric
      chelation affinity chromatography.
AB  - Protein kinase substrate phage (PKS phage) was constructed by fusing the
      substrate recognition consensus sequence of CAMP-dependent protein kinase (cAPK)
      with bacteriophage minor coat protein g3p and by displaying it on the surface of
      filamentous bacteriophage fd. Phosphorylationin vitro by cAPK showed a unique
      labelled band of approximately 60 ku, which was consistent with the molecular
      weight of the PKS-g3p fusion protein. Some weakly phosphorylated bands for both
      PKS phage and wild-type phage were also observed. Phage display random 15-rner
      peptide library phosphorylated by cAPK was selected with ferric (Fe(3+))
      chelation affinity resin. After 4 rounds of screening, phage clones were picked
      out to determine the displayed peptide sequences by DNA sequencing. The results
      showed that 5 of 14 sequenced phages displayed the cAPK recognition sequence
      motif (R)RXS/T. Theirin vitro phosphorylation analyses revealed the specific
      labelled bands corresponding to the positive PKS phages with and without the
      typical (R)RXS/T sequence motif. It suggested that the new method of using ferric
      (Fe(3+)) chelation affinity chromamraphy to identify the substrate specificity of
      protein kinase from random peptide library was feasible.

PMID- 18726316
TI  - Quenching of fluorescence in membrane protein by hypocrellin B.
AB  - The hypocrellin B (HB) was used as a fluorescence quencher to study the basic
      physical charactcristics of HB in membrane systems, including the diffusion speed
      of quencher from aqueous phase into membrane phase, the partition coefficient (P)
      of quenchtr between membrane and water, and the fluorescence quenching constant
      of protein (K(sv); K(q),). The experimental results show that the quenching of
      fluorescence in membrane protein by HB can be determined by the principle of
      dynamic quenching. The experimental process of fluorescence quenching was
      observed in detail by using the ESR technique. The signal of HB- was found to
      arise from an electron transfer from excited trytophan to HB.

PMID- 18726317
TI  - Sequential conformation change and activation of chicken liver dihydrofolate
      reductase in low concentration of guanidine hydrochloride.
AB  - The conformation changes of dihydrofolate reductase (DHFR) from chicken liver in
      guanidine hydrochloride were monitored by protein intrinsic fluorescence,
      hydrophobic fluorescence probe TNS and limited proteolysis by proteinase K. The
      kinetics of the enzyme denaturation were also studied and compared with its
      activity changes. It was indicated by the enhanced fluorescence of 2-p
      toluidinylnaphthalene (TNS) that a subtle conformational change of the enzyme in
      dilute GuHCl parallels GuHCl-induced activation. At GuHCl concentration higher
      than 0. 75 mol/L, the conformational change can be detected by increased
      susceptibility of the enzyme to proteinase K, but no significant gross
      conformational change of the enzyme molecule is observed by intrinsic
      fluorescence up to a GuHCl concentration of 1.2 mol/L. The results suggest that
      the denaturation of DHFR by GuHCl does not follow strictly the two-state model.
      The enzyme seems to open up sequentially with increasing concentrations of
      denaturants, mainly at the active site first, until to a critical concentration
      of the denaturant the overall conformation change of the molecule may occur
      cooperatively. Activation of DHFR in low GuHCl concentration is due to the subtle
      conformational change at the active site of the enzyme. Although the
      conformational change at the active site decreases the affinity of the enzyme for
      the substrates, it accelerates the velocity of the limiting step in the catalytic
      reaction, i.e. the velocity of the dissociation of products from the ternary
      complex.

PMID- 18726318
TI  - Sequence variation and genetic diversity in the giant panda.
AB  - About 336-444 bp mitochondrial D-loop region and tRNA gene were sequenced for 40
      individuals of the giant panda which were collected from Mabian, Meigu, Yuexi,
      Baoxing, Pingwu, Qingchuan, Nanping and Baishuijiang, respectively. 9 haplotypes
      were found in 21 founders. The results showed that the giant panda has low
      genetic variations, and that there is no notable genetic isolation among
      geographical populations. The ancestor of the living giant panda population
      perhaps appeared in the late Pleistocene, and unfortunately, might have suffered
      bottleneck attacks. Afterwards, its genetic diversity seemed to recover to some
      extent.

PMID- 18726319
TI  - Characterization of sequences downstream from transcriptional start site
      ofRhizobium meliloti nifHDK promoter.
AB  - In freeliving state, the nifHDK promoter P1 ofRhizbium meliloti is induced in
      response to microaerobiosis and expressed to a high level, while the fixABCX
      promoter P2 is not. The sequences upstream from both P1 and P2 share extended
      homology (about 85%), which are about 160 bp in length, but the sequences
      downstream of the respective transcriptional start site are different. When the
      downstream sequence (DS) of P2 was replaced by the corresponding fragment from+
      17 to + 61 of P1, the expression of P2 is greatly increased under freeliving
      condition by lowering the oxygen tension, and the activity of P2 promoter can
      also be significantly enhanced inE. coli by the NifA protein. The difference
      between the DS regions of P1 and P2 promoter resulted in different expressions of
      P1 and P2 promoter under freeliving microaerobic condition and inE. coli. The
      expression of P2 does not depend on the downstream sequences from the promoter
      element during symbiosis. Primer extension experiments identified the
      transcriptional start site of P2. Transcription from P2 was not changed when P2
      promoter region was inserted by P1 DS. Under symbiotic conditions, levels of
      expression of P2 were independent of the P1 DS region. It indicates that the
      regulations of P2 under symbiotic conditions are different from those under
      freeliving conditions.

PMID- 18726320
TI  - Fusion expression of mutated cecropin CMIV inE. coli.
AB  - A cDNA coding mutated cecropin CMIV fromBombyx mori was synthesized according to
      its amino acid sequence usingE. coli biased codons. The gene was cloned into the
      fusion expression vector pEZZ318 and was expressed inE. coli HB101. The fusion
      protein produced was purified by affinity chromatography to yield 26 mg/L fusion
      product. The anti-bacterial activities of recombinant cecropin CMIV were
      recovered after cleavage by chemical method.

PMID- 18726321
TI  - Combined therapy of p53-wt and drug in an orthotopic multidrug-resistant human
      lung cancer model.
AB  - Balb/c nu/nu mice were inoculated intratracheally with multidrug-resistant human
      lung cancer cells GLK containing p53 mutation at codon 245 and treated with
      intratracheal instillation of p53-wt retroviral vector (pDOR53W) to increase cell
      chemosensitivity, and then with intraperitoneal injection of doxorubicin. 30 d
      after tumor cell inoculation, 75% of the control mice showed macroscopic tumors
      in the lung. Sole pDOR53W suppressed GLK tumor formation in 68% of mice; sole
      doxorubicin 33.3%, but the combination of pDOR53W and doxorubicin 88.9 %. The
      exogenous p53 sequence was detected and confirmed in the tumor that grew after
      treatment with pDOR53W retroviral vector by PCR and Southern blot hybridization
      with p53 cDNA. These results suggested that direct administration of a retroviral
      vector expressing p53-wt combined with treatment of anticancer agent was an
      effective therapeutic method for multidrug-resistant human lung cancer.

PMID- 18726322
TI  - Regulation of purine biosynthetic genes expression inSalmonella typhimurium IV
      O(c) mutation site ofpurG and its function analysis.
AB  - Salmonella typhimurium 5 phosphoribosylformylglycinamide (FGAR) amidotransferase
      encoded bypurG gene catalyzes the conversion of FGAR to formylglycinamide
      ribonucleotide (FGAM) in the presence of glu- tamine and ATP for thede novo
      purine nucleotide biosynthesis.purG gene is negatively regulated by a repressor
      operator system. The O(+) purG and O(c) purG were cloned respectivelyin vivo.
      Restriction enzymes analysis of preliminary clones pLBG-1 (O(+)) and pLBG-2
      (O(c)) were carried out. The hybrid plasmids pLB1933 (O(+)) and pLB1927 (O(c))
      containing 5' control region ofpurG were constructed and the DNA sequences were
      determined respectively, DNA sequences data showed that O(c) mutation ofpurG
      occurred at the 3rd position of 16 bp PUR box in the 5' control region (G-->A).
      Gel retardation experiment indicated that the repressor bound well with O(+) PUR
      box, but not with O(c) PUR box. The result strongly supported the idea that PUR
      box is the binding region of repressor protein and the 3rd position base G of PUR
      box is essential for the binding function with repressor protein.

PMID- 18726323
TI  - In vivo transcription of two promoters, P(TH4) and P (TH270) involved in
      regulation ofStreptomyces differentiation.
AB  - The promoters, P(TH4) and P(TH270) involved in the regulation ofStreptomyces
      coelicolor differentiation were subcloned intoStreptomyces promoter, i.e. probe
      plasmid pIJ4083, and the recombinant plasmids, pIJ4470 and pIJ4471, were
      constructed. Two promoters could drive the expression of reporter gene encoding
      catechol dioxygenase when pIJ4470 and pIJ4471 were introduced into some white
      mutants (C85, C70, C71, C17 and C119). The total RNA was isolated from these
      strains containing recombinant plasmid. Probes were prepared by labelling 5'-ends
      of P(TH4) and P(TH270) DNA fragments using radioisotope. DNA -RNA hybridization
      was carried out with the probes and RNAs isolated from different strains. The S1
      mapping result showed that all RNAs from strains of C85/pIJ4470, C85/4471,
      C70/pIJ4470, C70/pIJ4471 and C17/pIJ4470 as well as C17/pIJ4471 gave rise to
      strong positive hybridization signal, whereas RNAs from C71/pIJ4470 and
      C71/pIJ4471 did not give any positive signal. RNAs from C119/pIJ4470 and
      C119/pIJ4471 gave weak hybridization signal. The result indicated that the
      transcription of both P(TH4) and P(TH270) promoters might depend onwhiG, an
      essential gene inStreptomyces differentiation, and partially depend on whiH, but
      they did not depend on other differentiation genes (whiA, whiB andurhiI).

PMID- 18726324
TI  - Conformation of 60-residue peptide fragment from N-terminal of porcine kidney
      fructose 1,6-bisphosphatase.
AB  - Limited digestion of fructose 1, 6-bisphosphatase with subtilisin produces an S
      peptide with an about 60-residue peptide fragment that is non-covalently
      associated with the enzyme. The 60-residue peptide fragment consists of the most
      part of allosteric site for AMP binding. It could be separated from S-protein by
      gel filtration with a Sephadex G-75 column equilibrated with 9% formic acid.
      According to X-ray diffraction results the S-peptide consists of two alpha
      helices without beta-strand and the alpha-helix content is about 60% in the 60
      residue-peptide fragment. When the enzyme is subjected to limited proteolysis
      with subtilisin, the secondary structure of the enzyme does not show a detectable
      change in CD spectrum. The CD spectra of the isolated S-peptide were measured
      under different concentrations. In the absence of GuHCl, S-peptide had 30% alpha
      helix and 38.5% turn-like structure but had no beta-strand, suggesting that the N
      terminal 60-residue fragment, which is synthesized initially by ribosome, would
      form a conformation spontaneously similar to that of the isolated 60-residue
      peptide, i.e. about 30% alpha-helix and 30% turn-like structure. As the
      elongation of the peptide chain of the enzyme proceeds, the newly synthesized
      segment or the final entire enzyme, in turn, affects the conformation of prior
      peptide segment and adjusts its conformation to the final native state. The
      content of alpha-helix did not increase as perturbing the conformation of S
      peptide by adding ethanol, cyclohexane or a small amount of SDS. On the contrary,
      the ordered structure was slightly decreased, indicating that the difference of
      conformations of S-peptide in the isolated form and in the associated protein was
      not an artifact produced by isolation process.

PMID- 18726325
TI  - Iron components in PS II particles of spinach by Mossbauer spectroscopy.
AB  - Mossbauer spectrum measured for the iron components of photosystem II (PS II)
      particles of spinach is a superposition of 4 doublets. Quadrupole splitting and
      chemical shifting of doublets I-IV are characteristics of proteins with oxidized
      cytochrome b-559, reduced cytochrome b-559, Fe(3+)-Q complex and Fe(2+) -Q
      complex respectively. After the PS II particles are treated with La(3+), two
      doublets of Fe(2+) disappear and Fe(2+) is converted into Fe(3+), indicating that
      the reduced cytochrome b-559 has been converted into the oxidized cytochrome b
      559, and Fe(2+) -Q complex into Fe(3+) -Q complex. The Mossbauer spectrum of PS
      II particles treated with La(3+) and Ca(2+) shows that Ca(2+) can weaken the
      inhibitory effect of La(3+) in part, and a portion of the reduced cytochrome b
      559 and Fe-Q complex still exist.

PMID- 18726326
TI  - The role of gamma-aminobutyric acid and its receptors in the nucleus of basal
      optic root in pigeons.
AB  - The effects of gamma-aminobutyric acid (GABA) and its antagonists bicuculline and
      2-hydroxysaclofen on neuronal firings in the nucleus of basal optic root (nBOR)
      in pigeons were studied by using extracellular recording and microiontophoretic
      techniques. The results suggest that GABA may be an inhibitory neurotransmitter
      or modulator within nBOR, functioning by means of main mediation of GABA(A)
      receptors and of minor mediation of GABA(B) receptors. Furthermore, GABA and its
      GABA(A) receptors are involved in the modulation of directional selectivity in
      part of nBOR neurons.

PMID- 18726327
TI  - Construction of expression vectors and study on single-chain antibody and
      reshaping single-domain antibody against CD3.
AB  - Two vectors, pWAI80 and pROH80, for expression of single-chain Fv fragments
      (ScFv) were constructed. The anti-CD3 VH and VL genes were amplified from UCHT1
      cells by RT-PCR and sequenced. Both genes were cloned in pWAI80 to express native
      ScFv and pROH80 for GST-ScFv fusion protein expression. The expression products
      were analysed by ELISA and Western blot. The combining site of OKT3 was modeled.
      Human Ig LS1 and Nd were selected as acceptors of CDRs of OKT3 VL and VH to
      construct a reshaping antibody against CD3. By comparing OKT3, LS1 and Nd with
      their own family sequences, some residues were changed and the reshaping VL and
      VH genes were designed. The full VH gene was assembled in three steps with eight
      chemically synthesized oligonucleotide fragments using overlapping PCR and
      sequenced. The VH gene was expressed as active protein in pCOMB3 and as inclusion
      bodies in pGEX-4T-1 by ELISA and Western blot analysis.

PMID- 18726328
TI  - Sequencing and bacterial expression of a novel murine alpha interferon gene.
AB  - A murine new alpha interferon gene (mIFN-alphaB) was found by primer-based
      sequencing method in a murine genomic DNA library. The gene was cloned and its
      sequence was determined. It was expressed inEscherichia coli under the control of
      the P(L) promoter which resulted in antiviral activity on mouse L-cells. The
      sequence of mIFN-alphaB has been accepted by GENEBANK.

PMID- 18726329
TI  - New red flower germplasm lines of cotton selected from hybrid ofGossypium
      hirsutum XG. bickii.
AB  - By means of dropping GA(3)(50 ppm) and NAA (40 ppm) on the hybrid boll-embryo
      culturein vitro, one F(1) plant ofG. hirsutum x G. bickii was obtained; when F(1)
      branches were grafted on upland cotton and then back-crossed with upland cotton
      under short-day and cooler-night condition, some BC(1) seeds could be harvested.
      The characteristic segregation was very violent in early generation. Through 3
      times of back-crossing and selecting, ten stable hybrid lines with the character
      of both male parent (viz. red petal-purple spot and strong fibre) and female
      parent (plant type, earliness, white fibre, lint length, etc.) were established.
      These lines were assigned as HB red flower lines (HBRL). Transference of
      character ofG. bickii to upland cotton was proved to be successful for the first
      time. These new germplasms may play an important role in both the genetic
      research and new cotton variety breeding.

PMID- 18726330
TI  - Construction of a novel fusion protein harboring mouse interferon gamma and
      epidermal growth factor receptor binding domain and enhancement of its antitumor
      activity.
AB  - A novel fusion protein harboring mouse interferon gamma and epidermal growth
      factor receptor binding domain was constructed with the method of genetic and
      protein engineering. The fusion protein kept complete antiviral activity with the
      titer of 10(8) IU per liter of culture. The EGF-RBD of the fusion protein
      exhibited competitive binding activity against(125)I-mEGF for mEGF receptors on
      A431 cells. The fusion protein was shown to be more potent in inhibiting the
      growth of cultured mouse breast carcinoma cells than interferon gamma.
      Experimental data on mouse B16 malignant melanoma model indicated that the tumor
      weight of fusion protein-treated group was statistically significantly smaller
      than that of interferon gamma -treated group. The work here provides a
      necessarily reliable clue for the upcoming clinical employment of a novel class
      of targeting interferons.

PMID- 18726331
TI  - Experimental study and mechanism analysis on bioeffects by nanosecond
      electromagnetic pulses.
AB  - The athermal bioeffects caused by nanosecond electromagnetic pulses with body
      cells was studied by using a broad band transverse EM-wave cell (BTEM CELL). The
      experimental system and preliminary mechanism analysis were presented.

PMID- 18726332
TI  - An analytical model for bidirectional reflectance factor of multicomponent
      vegetation canopies.
AB  - Based on radiative transfer theory in vegetation and geometric-optical
      principles, an analytical physical model for calculating multiangular,
      multispectral reflectance over a non-random, multiple component vegetation canopy
      is developed. This model is derived by taking advantages of the previous leaf
      canopy and multicomponent canopy BRF models. It quantitatively accounts for both
      the impact of foliage elements' orientation on the canopy hotspot through an
      innovative algorithm to estimate the hotspot function for any arbitrarily
      oriented foliage element and contributions of all foliage elements to the
      reflectance by multiple scattering. Thus, it is characterized by more completely
      considering the integrative influence of spatial variations in optical and
      structural properties of all foliage elements on canopy reflectance than any
      previous analytical BRF models. Simulation results from this model demonstrate
      that canopy hotspot becomes strongest when the mean inclination angle of foliage
      elements is around 20 degrees , and then it rapidly decreases with an increase in
      that angle. Comparison with field measured BRF data shows that this model can
      reproduce the angular asymmetrical distribution of canopy BRF, a feature of
      natural vegetation's reflectance which all leaf canopy models cannot reproduce.

PMID- 18726333
TI  - Transformation of maize embryogenic calli mediated by ultrasonication and
      regeneration of fertile transgenic plants.
AB  - An insecticidal protein gene isolated fromBacillus thuringiensis was transferred
      into maize by using ultrasonication. The fertile transgenic plants and their
      progeny were obtained. The Southern hybridization results indicated that the
      foreign gene had integrated into the maize genome. It has been found that the
      acoustic intensity and the duration of treatment are the important parameters
      influencing transformation efficiency by ultrasonication. The maximum relative
      transformation frequency of 34.1 % was achieved after 30 min of sonication at 0.
      5 W/cm(2) acoustic intensity. With appropriate parameters the ultrasonication can
      make a number of micropores formed on the cell surface and minimize the treatment
      damage to the foreign DNA molecules, thus facilitating the DNA molecules to enter
      the cells.

PMID- 18726334
TI  - Induction of small-segment-translocation between wheat and rye chromosomes.
AB  - A new approach to produce wheat-rye translocation, based on the genetic
      instability caused by monosomic addition of rye chromosome in wheat, is
      described. 1 283 plants from the selfed progenies of monosomic addition lines
      with single chromosome of inbred rye line R12 and complete chromosome complement
      of wheat cultivar Mianyang 11 were cytologically analyzed on a plant-by-plant
      basis by the improved C-banding technique. 63 of the plants, with 2n = 42, were
      found containing wheat-rye translocation or substitution, with a frequency of
      4.91%. Compared with the wheat parent, other 32 plants with 2n = 42 exhibited
      obvious phenotypic variation, but their component of rye chromosome could not be
      detected using the C-banding technique.In situ hybridization with a biotin-la
      beled DNA probe was used to detect rye chromatin and to determine the insertion
      sites of rye segments in the wheat chromosomes. In 20 out of the 32 variant wheat
      plants, small segments of rye chromosomes were found being inserted into
      different wheat chromosomes and form small-segment-translocation (SS
      translocation). The physical mapping of the translocated small segments of rye
      chromosomes indicated that alien insertion could occur in both the terminal and
      intermediate regions of wheat chromosomes. The technique described appeared to be
      an effective means to induce SS translocation. The wide application of SS
      translocation in the study of molecular cytogenetics and plant breeding is also
      discussed.

PMID- 18726335
TI  - Dedifferentiating initiation and embryogenesis from freshly-isolated microspores
      of barley.
AB  - By using DNA-specific fluorescent dye and a confocal laser scanning microscope,
      the present study was designed to investigate the cytological characteristics of
      dedifferentiating initiation during pretreatment and embryogenesis during culture
      in freshly-isolated microspores of barley, and the difference in main
      developmental pathway between freshly-isolated and cold-treated microspores. The
      results revealed that (i) freshly-isolated microspores started the initiation
      within 12 h of mannitol pretreatment, whose main cytological characteristics were
      that: cell volume was obviously extended; the volume of nuclei and nucleoli were
      also greatly increased; nucleoli were extremely clear and highly condensed; N/C
      ratio was very high; (ii) all the pretreatment methods led to the initiation of
      the microspores, thus triggering the embryogenic process; (iii) pretreatment
      methods influenced the main developmental pathway of microspores by changing the
      pattern of the first mitosis. The cold-treated microspores formed main
      developmental pathway via A patterns, but freshly-isolated microspores via B
      pattern.

PMID- 18726336
TI  - Theoretical investigation on peripheral ligands of oxygen-evolving center in
      photosystem II.
AB  - The interaction between the Mn-cluster and its peripheral ligands in oxygen
      evolving center is still unclear. Theoretical investigation on the coordination
      of histidine, H(2)O, and CI to Mn2O2 units in OEC is conducted. The following
      conclusions are obtained: (i) both histidine and H(2)O molecule, bound to the two
      Mn ions, respectively, are vertical to the Mn2O2 plane, and maintain a large
      distance; (ii) the two H(2)O molecules cannot bind to the same Mn2O2 unit. Based
      on Mn-cluster structure in OEC, we theoretically predict that two H(2)O molecules
      bind to the two Mn ions at the "C"-shaped open end in S(0) state, while two His
      residues at the closed end. Cl ion can only terminally ligate at the open end.
      Individual valence for the four Mn ions in S(0) state is assigned.

PMID- 18726337
TI  - Effect of light intensity on partitioning of photosynthetic electron transport to
      photorespiration in four subtropical forest plants.
AB  - Photosynthetic rate (P(n)) and the partitioning of noncyclic photosynthetic
      electron transport to photorespiration (J(O)) in seedlings of four subtropical
      woody plants growing at three light intensities were studied in the summer time
      by measurements of chlorophyll fluorescence and CO(2) exchange. Except Schima
      superba, an upper canopy tree species, the tree species Castanopsis fissa and two
      understory shrubs Psychotria rubra, Ardisia quinquegona had the highest P (n) at
      36% of sunlight intensity. The total photosynthetic electron transport rate
      (J(F)) and the ratio of J (O)/J(F) were elevated in leaves under full sunlight.J
      (O)/J(F) ratio reached 0.5-0.6 and coincided with the increasing of oxygenation
      rate of Rubisco (V(O)), the activity of glycolate oxidase and photorespiration
      rate at full sunlight. It is suggested that an increasing partitioning proportion
      of photosynthetic electron transport to photorespiration might be one of the
      protective regulation mechanisms in forest plant under strong summer light and
      high temperature conditions.

PMID- 18726338
TI  - Simulated biological effects of microgravity on phospholipid and energy
      metabolism of chicken embryonic brain cells studied by(31)P-NMR spectroscopy.
AB  - Levels of phosphomonoester (PME), phosphodiester (PDE), ATP and pH in brain cells
      of chicken embryos rotated for 24 h in a clinostat during the period of hatching
      the 13th day (E13) and 15th day (E15) embryos were investigated by using(31)P-NMR
      spectroscopy. Significant increases in the values of PME, ATP and pH were
      identified after E13 rotating for 24 h. With the same treatment, differences were
      obtained in the phospholipid and energy metabolism of E15, but no significant
      levels have been reached. The calorimetric assay (malachite green method) was
      used for measuring the activity of total ATPase. A dramatic decrease was evident
      in the activity of ATPase in brain cells of rotated E13 and E15. The former is
      more sensitive than the latter. All the levels mentioned above could restore in
      24 h after the rotation stopped, except that the level of ATP was still higher
      than the control.

PMID- 18726339
TI  - Introduction of a rice blight resistance gene,Xa21, into five Chinese rice
      varieties through an Agrobacterium-mediated system.
AB  - A cloned gene, Xa21 was transferred into five widely-used Chinese rice varieties
      through an Agrobacterium- mediated system, and over 110 independent transgenic
      lines were obtained. PCR and Southern analysis of transgenic plants revealed the
      integration of the whole Xa21 gene into the host genomes. The integrated Xa21
      gene was stably inherited, and segregated in a 3: 1 ratio in the selfed T(1)
      generation when one copy of the gene was integrated in the transformants.
      Inoculation tests displayed that transgenic T(0) plants and Xa21 PCR-positive
      T(1) plants were highly resistant to bacterial blight disease. The selected Xa21
      homozygous resistant transgenic lines with desirable qualities may be propagated
      as new varieties or utilized in hybrid rice breeding.

PMID- 18726340
TI  - Molecular mapping of split rice spikelet mutant srs-1 and analysis of its
      homeotic function in rice.
AB  - srs-1, a new floral organ identity gene in rice, was mapped using RAPD and RFLP
      markers. Firstly, the cross was made between "ZhaiYeQing 8" (ZYQ8, indica) and
      split rice spikelet (SRS, japonica) mutant. The ratio of wild-type individuals
      and mutant plants in F(2) population is 3:1, which indicates that the mutant
      characteristics are controlled by single recessive gene,srs-1. Consequently, BSA
      method was adopted and 520 random 10-mer primers were used to screen polymorphic
      bands between two bulks. Six primers could amplify polymorphic bands, of which
      S465 generates the most stable RAPD patterns. Then, S465 that cosegregates in
      F(2) population has been converted into an RFLP marker successfully.
      Furthermore,srs-1 gene was mapped on chromosome 3 using DH mapping population.
      The effect of srs-1 gene results in the mutant of split rice spikelet. The mutant
      has longer and softer palea/lemma than those of wild-type, and two small
      palea/lemma-like organs between palea and lemma. In addition, there is a flower
      with three stamens and carpel in the axil of lemma. Thus, there are nine stamens
      and two carpels in the spikelet of mutant,srs-1 gene may belong to homeotic gene
      of class A according to the mutant characteristics and ABC model.

PMID- 18726341
TI  - Structure and function of sawB, a gene involved in differentiation of
      Streptomyces ansochromogenes.
AB  - A partial DNA library of Streptomyces ansochromogenes 7100 was constructed by
      using plasmid pl J702 as vector and white mutant W19 as recipient. About 3 000
      clones were obtained, two of which gave rise to the grey phenotype as wild type
      7100. The plasmids were isolated from two transformants. The result indicated
      that the 5.2 kb and 5.8 kb DNA fragments were inserted into plJ702. The resulting
      recombinant plasmids were designated as pNL-1 and pNL-2 respectively. The 1.25 kb
      Pstl I -Apa I DNA fragment from pNL-1 was recognized as its complementarity to
      W19 strain. The nucleotide sequence of the 3.0 kb Pst I DNA fragment including
      1.25 kb was determined and analyzed. The result indicated that this DNA fragment
      contains one complete open reading frame (ORF1) which encodes a protein with 295
      amino acid residues, and this gene was designated as sawB. The deduced protein
      has 81% amino acid identities in comparison with that encoded by whiH in
      Streptomyces coelicolor. The function of sawB gene was studied by using strategy
      of gene disruption, and the resulting sawB mutant failed to form spores and
      produced loosely coiled aerial hyphal. The result showed that sawB is closely
      related to hyphal coiling and sporulation in S. ansochromogenes, and also
      indicated that the sawB can complement whiH mutant (C119) to restore the grey
      phenotype of Streptomyces coelicolor J 1501 (wild type).

PMID- 18726342
TI  - Regeneration of foreign genes co-transformed plants of Medicago sativa L by
      Agrobacterium rhizogenes.
AB  - Gene encoding sulphur amino acid-rich protein (HNP) and rol genes were
      transferred into Medicago sativa L (alfalfa) mediated by Agrobacterium
      tumafeciens. Regeneration of transgenic plants was induced successfully from
      hairy root tissue of cotyledon in alfalfa. Cotyledon tissues were an ideally
      transformed recipient. There was a negative correlation between age of hairy
      roots and embryogenesis frequency in alfalfa. Production of co-transformed plants
      with greater yield and super quality was important for development of new alfalfa
      varieties.

PMID- 18726343
TI  - Molecular cloning and expression analysis of HAG1 in the floral organs of
      Hyacinthus orientalis L.
AB  - HAG1 gene was isolated from the floral organs of Hyacinthus orientalis L. by
      using RT-PCR. Sequence analysis showed that this gene was homologous to AGAMOUS.
      Northern hybridization indicated that HAG1 was specifically expressed in floral
      organs using 3' end of HAG1 as a probe. Further, transcript of this gene was not
      detected in differentiating tepals induced by lower concentration of hormones,
      however, it was detected in differentiating stemans by higher concentration of
      hormones in vitro. It is possible that there is a close relationship between the
      concentration of hormones, homeotic genes and identities of floral organs.

PMID- 18726344
TI  - Golgi 58K-like protein in pollens and pollen tubes of Lilium davidii.
AB  - In animal cells, Golgi apparatus is located near the microtubule organizing
      center (MTOC) and its position is determined partly by 58K protein. By sodium
      dodecyl-sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immuno-blotting
      methods, a 58K-like protein has been found in pollen grains and pollen tubes of
      Lilium davidii. Its molecular weight is very similar to that of the 58K protein
      of animal cells. By immunofluorescence labeling, under a confocal laser scanning
      microscope (CLSM), the animal 58K antibody revealed a punctate staining in pollen
      grains and pollen tubes, which is consistent with the distribution of Golgi
      apparatus in plant cells. In addition, immuno-gold labeling and transmission
      electron microscopy showed that the 58K-like protein bound mainly to the membrane
      of vesicles-like structure near Golgi apparatus. This is the first demonstration
      of the 58K-like protein in plant cells.

PMID- 18726345
TI  - Prediction on the binding domain between human interleukin-6 and its receptor.
AB  - Based on the spatial conformations of human interleukin-6 (hIL-6) derived from
      nuclear magnetic resonance analysis and human interleukin-6 receptor (hIL-6R)
      modeled with homology modeling method using human growth hormone receptor as
      template, the interaction between hIL-6 and its receptor (hIL-6R) is studied with
      docking program according to the surface electrostatic potential analysis and
      spatial conformation complement. The stable region structure composed of hIL-6
      and hIL-6R is obtained on the basis of molecular mechanism optimization and
      molecular dynamics simulation. The binding domain between hIL-6 and hIL-6R is
      predicted theoretically. Furthermore, the especial binding sites that influence
      the interaction between hIL-6 and hIL-6R are confirmed. The results lay a
      theoretical foundation for confirming the active regions of hIL-6 and designing
      novel antagonist with computer-guided techniques.

PMID- 18726346
TI  - Cloning of a regulatory gene from Streptomyces cattleya and study on its cis
      acting element.
AB  - Primers were designed from the highly conserved protein regions of luxl, one of
      the two component regulatory genes in prokaryotic, and an about 180 bp DNA from
      Streptomyces cattleya was amplified by PCR. Using this fragment as a probe,
      Southern hybridization was accomplished with chromosome DNA of S. cattleya,
      leading to the cloning of the foreign DNA into pBluescript (SK-). DNA sequencing
      and frame analysis showed an intact ORF consisting of 1800 bp; the G+C
      composition was 69.3%. Upstream from the ORF was a 249 bp AT rich region,
      downstream of the ORF several complicated secondary structures were found. DNA
      binding assay by gel retardation demonstrated the presence of a protein that
      specifically bound to the 249 bp AT rich region. The region also showed anomalous
      electrophoretic mobility at low temperature, like that of a bent DNA molecule,
      indicating that the region contains a cis-acting element.

PMID- 18726347
TI  - Three-dimensional structure and function study on the active region in the
      extracellular ligand-binding domain of human IL-6 receptor.
AB  - In this study the three-dimensional (3-D) model of the ligand-binding domain
      (V106-P322) of human interleukin-6 receptor (hIL-6 R) was constructed by computer
      guided homology modeling technique using the crystal structure of the ligand
      binding domain (K52-L251) of human growth hormone receptor (hGHR) as templet.
      Furthermore, the active binding region of the 3-D model of hIL-6R with the ligand
      (hIL-6) was predicted. In light of the structural characteristics of the active
      region, a hydrophobic pocket shielded by two hydrophilic residues (E115 and E505)
      of the region was identified by a combination of molecular modelling and the site
      directed or double-site mutation of the twelve crucial residues in the ligand
      binding domain of hIL-6R (V106-P322). We observed and analyzed the effects of
      these mutants on the spatial conformation of the pocket-like region of hIL-6 R.
      The results indicated that any site-directed mutation of the five Cys residues
      (four conservative Cys residues: Cys121, Cys132, Cys165, Cys176; near membrane
      Cys residue: Cys193) or each double-site mutation of the five residues in WSEWS
      motif of hIL-6R (V106-P322) makes the corresponding spatial conformation of the
      pocket region block the linkage between hIL-6 R and hIL-6. However, the influence
      of the site-directed mutation of Cys211 and Cys277 individually on the
      conformation of the pocket region benefits the interaction between hIL-6R and hIL
      6. Our study suggests that the predicted hydrophobic pocket in the 3-D model of
      hIL-6R (V106-P322) is the critical molecular basis for the binding of hIL-6R with
      its ligand, and the active pocket may be used as a target for designing small hIL
      6R-inhibiting molecules in our further study.

PMID- 18726348
TI  - Intracellular expression of a single-chain antibody directed against type IV
      collagenase inhibits the growth of lung cancer xenografts in nude mice.
AB  - It was documented that type IV collagenase with two subtypes of 72 ku/MMP-2 and
      92 ku/MMP-9 plays an important role in tumor invasion and metastasis. The
      endoplasmic reticulum (ER)-retained, single chain Fv antibody fragment (scFv) was
      used to inhibit the function of type IV collagenase. For expression in mammalian
      cells, the assembled scFv M97 gene with ER retention signal encoding 6 additional
      amino acids (SEKDEL) was reamplified by PCR. The amplified fragments were cloned
      into the pcDNA3.1 vector. The resulting plasmid was sequenced and then introduced
      into PG cells, a highly metastatic human lung cancer cell line, by lipofectAMINE
      method. The result of intrabody gene therapy showed that type IV collegenase
      expression was down regulated significantly as measured by ELISA. The biological
      behavior of PG cell, such as the ability of in vitro invasion through Matrigel,
      colony formation on soft agar, was also inhibited by scFv M97 transfection.
      Animal experiments in a xenograft model of human lung cancer showed that scFv M97
      transfection significantly prolonged the survival time of nude mice. The results
      indicate that intracellular antibody technology represents a novel and efficient
      way to abrogate selectively the activity of type IV collagenase.

PMID- 18726349
TI  - Cloning and characterization of a cDNA encoding human differentiation antigen
      5D4.
AB  - A 1 846 bp cDNA is isolated from a human tonsil cell lambda gt 11 cDNA library
      (ATCC No. 37546) with mAb 5D4 reactive strongly with human B cell line 3D5, but
      weakly with human B cell line Daudi and human T cell line Jurkat as a probe. RT
      PCR also shows a strong reaction in 3D5 cell and a weak reaction in Daudi and
      Jurkat cell for 5D4 mRNA. There is an open reading frame from 88 to 1 209 bp in
      5D4 cDNA encoding a 374 AA protein. Both the Northern blot analysis and the two
      consecutive stop codens before start coden demonstrate that the cDNA is a full
      length cDNA. Secondary structure prediction suggests that there are a region from
      295 to 334 AA in the protein with strong hydrophobicity and a transmembrane helix
      region with high score from 313 to 334 AA with an orientation from the inside to
      the outside of the cell.

PMID- 18726350
TI  - Identification of phosphorylation sites of proteins by high performance liquid
      chromatography-electrospray ionization-quadrupole ion trap mass spectrometry.
AB  - The phosphorylation sites of two phosphorylated proteins, bovine beta-casein and
      myelin basic protein (MBP), were identified by high performance liquid
      chromatography-electrospray ionization-quadrupole ion trap mass spectrometry
      (HPLC-ESI-QITMS). The tryptic digest of each protein was separated by HPLC, the
      molecular weight of each peptide was determined by ESI-QITMS on line, and MS/MS
      spectrum of each peptide was simultaneously obtained by the combination of
      collision-induced desorption (CID) technique and tandem mass spectrometry (MS/MS)
      of QITMS. The phosphorylated peptide was identified by looking into whether the
      difference between the observed and predicted molecular weights of a peptide is
      80 u or its integral multiple. Then the phosphorylation site was identified
      through manual interpretation of the MS/MS spectrum of the phosphorylated peptide
      or automatic SEQUEST data base-searching.

PMID- 18726351
TI  - Comparative study on direction selectivity and functional organization of the
      primary visual cortical cells in monkeys and cats.
AB  - Although the directionally selective cells in many visual cortical areas are
      organized in columnar manner, the functional organization of direction
      selectivity of area Vl in the monkey still remains unclear. We quantitatively
      studied the proportion of directionally selective cells, direction selectivity
      and the functional organization of the striate cortical cells in the monkey and
      compared those with the cat. The results show that the direction selectivity and
      directional organization of striate cortical cells in the monkey are
      significantly weaker than those in the cat, suggesting that the species
      difference between the two kinds of animal is related to their different anatomic
      pathways.

PMID- 18726352
TI  - Promoting effect of IFN-gamma on the expression of LPS-induced IL-12 p40 and p35
      mRNA in murine suppressor macrophages.
AB  - We detected the expression of IL-12 p40/p35 mRNA by semi-quantitative RT-PCR and
      silver staining, and studied the molecular interaction between the IL-12
      expression and the NF-eB activation induced by LPS and IFN-gamma/LPS in murine
      peritoneal suppressor macrophages (MPSMs). It was found that IFN-gamma strongly
      enhanced the LPS-induced IL-12 p40 and p35 mRNA expression. Both p40 and p35 mRNA
      levels were approximately equal. IFN-a also greatly promoted the LPS-induced
      secretion of IL-12 p70 in MPSMs. The Proteasome Inhibitor I (PSI) could block the
      expression of IL-12 p40 and p35 mRNA, and the degradation of IkappaBalpha induced
      by LPS or LPS/IFN-gamma. EMSA showed that LPS could augment the NF-kappaB binding
      activity to p40 promoter DNA. However, IFN-gamma could neither enhance the LPS
      induced NF-kappaB activity nor promote the degradation of IkappaBalpha. Taken
      together, the data suggest: (i) IFN-gamma/LPS could strongly induce the
      expression of IL-12 p40 and p35 mRNA; both the expression levels were equal; this
      phenomenon coincided with the high-level secretion of IL-12 p70 induced by IFN
      gamma/LPS; (ii) NF-kappaB signal pathway is essential for IFN-gamma/LPS to induce
      IL-12 mRNA expression; (iii) by blocking the degradation of IkappaB, the PSI
      suppresses the IL-12 p40/p35 mRNA expression induced by LPS and IFN-gamma/LPS;
      (iv) NF-kappaB signal may not be involved in the mechanism by which IFN-gamma
      enhanced the expression of the LPS-induced IL-12 p40/p35 mRNA.

PMID- 18726353
TI  - Sequence of mitochondrial DNA cytochrome oxidase II inCryptopygus nanjiensis and
      Phylogeny of Apterygota.
AB  - The mitochondrial cytochrome oxidase II (Co II) from four different
      apterygotensCryptopygus nanjiensis (Collembola),Neanura latior
      (Collembola),Gracilentulus maijiawensis (Protura) andLepidocampa weberi (Diplura)
      were sequenced. Their A+T content, number of nucleotide substitutions, TV/TV
      ratio, and Tamura-Nei's distance were calculated. A series of phylogenetic trees
      were constructed by parsimony and distance methods using a crustaceanArtemia
      franciscana as outgroup. Finally the evolutionary trend A+T content of CO II
      genetic divergence and phylogenetic relationship of apterygotan groups were
      discussed.

PMID- 18726354
TI  - The onset of foreign gene transcription in nuclear-transferred embryos of fish.
AB  - The transcriptional onset ofhGH-transgene in fish was studied in the following
      three cases: the first is inMThGH-transgenic F(4) common carp (Cyprinus carpio)
      embryos, the second is in nuclear-transferred embryos supported by the transgenic
      F(4) embryonic nuclei, and the third is in nuclear-transferred embryos supported
      by the transgenic F(4) tail-fin nuclei. RT-PCR results show that thehGH-transgene
      initiates its transcriptional activity from early-gastrula stage, the early
      blastula stage and even 16-cell stage in the first, second and third cases,
      respectively. It looks like that fish egg cytoplasm could just offer a very
      restricted reprogramming on transcriptional activity of specific gene in
      differentiated cell nuclei by nuclear transplantation.

PMID- 18726355
TI  - Comparative study on the responses of maxillary sensilla styloconica of cotton
      bollwormHelicoverpa armigera and Oriental tobacco budwormH. assulta larvae to
      phytochemicals.
AB  - Using the electro-physiological technique, the sensory mechanisms of maxillary
      sensilla styloconica to stimulants and deterrents were explored on two closely
      related species, the generalistHelicoverpa armigera and the specialistH. assulta.
      The results showed that: (i) in both species, cells sensitive to sucrose and
      azadirachtin were mainly in the lateral sensillum styloconicum, and those to
      inositol were in the medial sensillum styloconicum; (ii) sensitivity of medial
      sensillum styloconicum inH. assulta to inositol was higher than that inH.
      armigera; (iii) among 6 tested deterrents, only azadirachtin evoked high impulse
      discharge from the lateral sensillum styloconicum in both insects; (iv) the
      deterrents could disturb stimulants evoking impulse discharge from maxillary
      sensilla styloconica of both species in different degrees: To sucrose evoking
      impulses on lateral sensillum styloconicum, forH. armigera capsaicin had a strong
      inhibition and gossypol had a weak inhibition, while forH. assulta tannic acid,
      gossypol, and tomatine all had strong inhibition except nicotine and capsaicin;
      to inositol evoking impulses on medial sensilum styloconicum, forH. armigera
      inhibition of tomatine was strong but that of gossypol was weak; and forH.
      assulta inhibition of gossypol was strong but that of nicotine was weak.

PMID- 18726356
TI  - cDNA cloning, chromosome mapping and expression characterization of human
      geranylgeranyl pyrophosphate synthase.
AB  - Geranylgeranyl pyrophosphate (GGPP) mainly participates in post-translational
      modification for various proteins including Rho/Rac, Rap and Rab families, as
      well as in regulation for cell apoptosis. Geranylgeranyl pyrophosphate synthase
      (GGPPS), which catalyzes the condensation reaction between farnesyl diphosphate
      and isopentenyl diphosphate, is the key enzyme for synthesizing GGPP. We report
      the isolation of a gene transcript showing high homology withDrosophila GGPPS
      cDNA. The transcript is 1 466 bp in length and contains an intact open reading
      frame (ORF) ranging from nt 239 to 1 138. This ORF encodes a deduced protein of
      300 residues with calculated molecular weight of 35 ku. The deduced protein shows
      57.5% identity and 75% similarity withDrosophila GGPPS, and contains five
      characteristic domains of prenyltransferases. Northern hybridization revealed
      that humanGGPPS was expressed highest in heart, and moderately in spleen, testis,
      brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. No obvious
      bands were detected in other examined tissues. TheGGPPS gene was located on human
      chromosome 1q43 by Radiation Hybrid mapping method. It was proved that there was
      a putative predisposing gene for prostate cancer in this region, and that analogs
      of GGPP can inhibit the geranylgeranylation of p21rap protein in PC-3 prostate
      cancer cell lines. These facts suggest thatGGPPS may be one of the candidate
      genes for prostate cancer.

PMID- 18726357
TI  - A comparative analysis ofafuzzless-lintless mutant ofGossypium hirsutum L. cv. Xu
      142.
AB  - Afuzzless-lintless (fl) seed mutant ofGossypium hirsutum L. cv. Xu-142 was
      investigated to study cotton fiber development. Scanning electron microscopy
      revealed that fiber initials were virtually absent fromfl ovules. RT-PCR analysis
      showed that the steady-state levels of transcripts of the fiber-specificE6
      andExpansin genes were high in wild type (WT) ovules during the fiber initiation
      and elongation stages, and peaked around 15 days post anthesis (DPA), but only a
      trace amount of these transcripts was detectable infl ovules of all developmental
      stages investigated.CotmybA, a member of theMyb family, exhibited a clear
      expression in developing WT ovules, but the expression was abnormal infl ovules.
      Application of GA(3), or GA(3) plus IAA, to the culture medium rescuedin vitro
      fiber initiation and growth offl ovules only partially. In addition,
      transcription ofE6 andExpansin genes ofin vitro cultured WT andfl ovules
      responded similarly to exogenous hormones. The hormones had less effect onCotmybA
      transcription in ovules culturedin vitro, and again the WT andfl ovules showed a
      similar expression. These results suggest that the abnormal or extremely low
      level of expression ofE6, Expansin andCotmybA genes in developingfl seeds is
      related to the absence of seed-hairs, and the mechanism underlying needs further
      investigation.

PMID- 18726358
TI  - Interactions between HMG proteins and the core sequence of DNaseI hypersensitive
      site 2 in the locus control region (LCR) of the human beta-like globin gene
      cluster.
AB  - HMG proteins are abundant chromosomal non-histone proteins. It has been suggested
      that the HMG proteins may play an important role in the structure and function of
      chromatin. In the present study, the binding of HMG proteins (HMG1/2 and
      HMG14/17) to the core DNA sequence of DNaseI hypersensitive site 2 (HS2core DNA
      sequence, -10681-10970 bp) in the locus control region (LCR) of the human beta
      like globin gene cluster has been examined by using both thein vitro nucleosome
      reconstitution and the gel mobility shift assays. Here we show that HMG1/2 can
      bind to the naked HS2core DNA sequence, however, HMG14/17 cannot. Using thein
      vitro nucleosome reconstitution we demonstrate that HMG14/17 can bind to the
      HS2core DNA sequence which is assembled into nucleosomes with the core histone
      octamer transferred from chicken erythrocytes. In contrast, HMG1/2 cannot bind to
      the nucleosomes reconstitutedin vitro with the HS2core DNA sequence. These
      results indicate that the binding patterns between HMG proteins and the HS2core
      DNA sequence which exists in different states (the naked DNA or thein vitro
      reconstituted nucleosomal DNA) are quite different. We speculate that HMG
      proteins might play a critical role in the regulation of the human beta-like
      globin gene's expression.

PMID- 18726359
TI  - Identification and cloning of the cDNA of a Rb-associated protein RAP140a.
AB  - Rb exerts important physiological functions in cell-cycle control, gene
      expression, cell differentiation, apoptosis, development and tumorigenesis by
      interacting with many cellular proteins. Using human partial Rb as bait, we
      screened a human fetal brain cDNA library through yeast two-hybrid system and
      obtained six novel cDNA fragments. Among them, one cDNA fragment corresponds to
      two different transcripts, 7 kb and 9 kb in Northern blot analysis. These two
      transcripts showed uniform distribution in various human tissues. We cloned the
      full-length cDNA of a 7.2 kb transcript through three times PCR amplifications.
      It was namedRAP140a and predicted to encode a 1 233 amino acids hydrophilic
      protein.RAP140a was mapped to chromosome 3p13-p14. 1. RAP140a may be functionally
      related to the intracellular translocation of Rb or other proteins.

PMID- 18726360
TI  - Cloning and characterization of a novel deletion mutant of heterogeneous nuclear
      ribonucleoprotein M4 from human dendritic cells.
AB  - To identify differentially expressed genes from antigen-stimulated human
      dendritic cells (DC), subtractive cloning was adopted and more than ten novel
      genes differentially expressed were cloned. One is a deletion mutant of
      heterogeneous nuclear ribonucleoprotein (hnRNP) M4 in which the residues from 159
      to 197 of hnRNP M4 have been absent. The deletion mutant was shown to be co
      expressed with hnRNP M4 in cell lines. The mutant was expressed in antigen
      stimulated DC but not in normal DC. Northern blot analysis revealed the presence
      of a major hnRNP M4 deletion mutant mRNA transcript of 2.4 kilobase with the
      highest levels in peripheral lymphocytes, lung, liver and spleen. It was also
      expressed in bone marrow-derived stromal cells (BMSC), BMSC treated with several
      cytokines but not in BMSC treated with TNF-alpha. The results revealed a new
      member of hnRNP family and suggested that hnRNP would participate in antigen
      process and presentation.

PMID- 18726361
TI  - Mediation by calcium/calmodulin-dependent protein kinase II of suppression of
      GABA(A) receptors by NMDA.
AB  - Using nystatin-perforated whole-cell recording configuration, the modulatory
      effect of N-methyl-D-aspartate (NMDA) on gamma-aminobutyric acid (GABA)-activated
      whole-cell currents was investigated in neurons freshly dissociated from the rat
      sacral dorsal commissural nucleus (SDCN). The results showed that: (i) NMDA
      suppressed GABA-and muscimol (Mus)-activated currents (I(gaba) and I(Mus)),
      respectively in the Mg(2+)-free external solution containing 1 mumol/L glycine at
      a holding potential (V ( H )) of -40 mV in SDCN neurons. The selective NMDA
      receptor antagonist, D-2-amino-5-phosphonovaleric acid (APV, 100 gammamol/L),
      inhibited the NMDA-evoked currents and blocked the NMDA-induced suppression of
      I(gaba); (ii) when the neurons were incubated in a Ca(2+)-free bath or pre-loaded
      with a membrane-permeable Ca(2+) chelator, BAPTA AM (10 mumol/L), the inhibitory
      effect of NMDA on I(GAba) disappeared. Cd(2+) (10 mumol/L) or La(3+) (30
      mumol/L), the non-selective blockers of voltage-dependent calcium channels, did
      not affect the suppression of I(gaba) by NMDA application; (iii) the suppression
      of I(GAba) by NMDA was inhibited by KN-62, a calcium/calmodulin-dependent protein
      kinase II (CaMKII) inhibitor. These results indicated that the inhibition of GABA
      response by NMDA is Ca(2+)-dependent and CaMKII is involved in the process of the
      Ca(2+)-dependent inhibition.

PMID- 18726362
TI  - Inhibition of the growth of human hepatoma cell line bothin vitro andin vivo by
      transducing CKI genep21 ( WAF-1 ) with GE7 targeting gene delivery system.
AB  - The EGF receptor-mediated targeting gene delivery system GE7 was used to
      transduce exogenous genepCEP-p21 ( WAF-1 ) into human hepatocellular carcinoma
      cell bothin vitro andin vivo. Afterin vitro transduction of the exogenous gene,
      the growth of the cell lines SMMC-7721 and BEL-7402 was significantly inhibited
      compared with the control. On day 8 the inhibition rates of the above cell lines
      reached 56.0% and 66.7%, respectively. Thein vivo experiment showed that the
      growth of human hepatoma transplanted in nude mice injected with GE7 gene
      delivery system subcutaneously once a week for 3 weeks was remarkably inhibited
      compared with that of untransfected control. The average tumor weight of the
      experiment group was (0.083 +/-0.043) g, while that of the control group was
      (0.281 +/-0.173) g. The difference is significant (P<0.05). It was indicated that
      GE7 gene delivery system could efficiently transduce exogenous genepCEP-p21 ( WAF
      1 ) into hepatoma cell with high EGF receptor expression, and inhibit the cell
      growth with high efficacy bothin vivo andin vitro.

PMID- 18726363
TI  - Genetic analysis of morphological index and its related taxonomic traits for
      classification of indica/japonica rice.
AB  - A doubled haploid population derived from anther culture of ZYQ8/JX17 F(1), a
      typical indica and japonica hybrid, was used in this study. Morphological index
      and its related taxonomic traits were investigated in 121 DH lines. The
      quantitative trait loci (QTLs) for morphological index and its related taxonomic
      traits were analyzed. Two major QTLs for leaf hairiness, three QTLs for
      length/width of grain, one QTL for color of hull when heading, one QTL for
      hairiness of hull, two QTLs for length of the first and second panicle internode,
      and one major QTL and two QTLs for phenol reaction were detected. Four QTLs for
      morphological index were also identified on chromosomes 1, 3, 4 and 6,
      respectively, three of which on chromosomes 1, 3 and 6, respectively, were found
      to be located in the same chromosome regions where some QTLs for the related
      taxonomic traits were located.

PMID- 18726364
TI  - Conservation of ribosomal protein gene ordering in 16 complete genomes.
AB  - The organization of ribosomal proteins in 16 prokaryotic genomes was studied as
      an example of comparative genome analyses of gene systems. Hypothetical ribosomal
      protein-containing operons were constructed. These operons also contained
      putative genes and other non-ribosomal genes. The correspondences among these
      genes across different organisms were clarified by sequence homology
      computations. In this way a cross tabulation of 70 ribosomal proteins genes was
      constructed. On average, these were organized into 9-14 operons in each genome.
      There were also 25 non-ribosomal or putative genes in these mainly ribosomal
      protein operons. Hence the table contains 95 genes in total. It was found that:
      (i) the conservation of the block of about 20 r-proteins in the L3 and L4 operons
      across almost the entire eubacteria and archaebacteria is remarkable; (ii) some
      operons only belong to eubacteria or archaebacteria; (iii) although the ribosomal
      protein operons are highly conserved within domain, there are fine variations in
      some operons across different organisms within each domain, and these variations
      are informative on the evolutionary relations among the organisms. This method
      provides a new potential for studying the origin and evolution of old species.

PMID- 18726365
TI  - Molecular phylogenetic systematics of twelve species of Acipenseriformes based on
      mtDNA ND4L-ND4 gene sequence analysis.
AB  - Acipenseriformes is an endangered primitive fish group, which occupies a special
      place in the history of ideas concerning fish evolution, even in vertebrate
      evolution. However, the classification and evolution of the fishes have been
      debated. The mitochondrial DNA (mtDNA) ND4L and partial ND4 genes were first
      sequenced in twelve species of the order Acipenseriformes, including endemic
      Chinese species. The following points were drawn from DNA sequences analysis: (i)
      the two species of Huso can be ascribed to Acipenser, (ii) A. dabryanus is the
      mostly closely related to A. sinensis, and most likely the landlocked form ofA.
      sinensis; (iii) genus Acipenser in trans-Pacific region might have a common
      origin; (iv) mtDNA ND4L and ND4 genes are the ideal genetic markers for
      phylogenetic analysis of the order Acipenseriformes.

PMID- 18726366
TI  - Fine-mapping of an Arabidopsis cell death mutation locus.
AB  - An Arabidopsis cell death mutation locus was mapped to chromosome 2 between /GS1
      and mi421. The YAC clone ends, CIC9A3R, CIC11C7L, CIC2G5R and RFLP marker CDs3
      within this interval, were used to probe TAMU BAC library and 31 BAC clones were
      obtained. A BAC contig encompassing the mutation locus, which consists of T6P5,
      T7M23, T12A21, T8L6 and T18A18, was identified by Southern hybridization with the
      BAC ends as probes. 11 CAPS and 12 STS markers were developed in this region.
      These results will facilitate map-based cloning of the genes and sequencing of
      the genomic DNA in this region.

PMID- 18726367
TI  - Determination of phylogenetic position of Pipizini (Diptera: Syrphidae): based on
      molecular biological and morphological data.
AB  - Based on the sequence analysis of 5.8S subunit and internal transcribed spacers
      (ITS) of ribosomal RNA gene (rDNA), the molecular phylogenetic tree of
      representative species of Pipizini and three groups of Syrphidae with different
      feeding habits (seven species belong to six genera) was constructed. Meanwhile,
      the phylogenetic tree of tribes (including Pipizini and other 17 tribes of
      Syrphidae) was constructed using morphological characteristics of adults and
      larvae and the number of chromosomes. Both the results show that the relationship
      between Pipizini and predatory groups is closer than that between Pipizini and
      saprophagous groups. So it is suggested that Pipizini be transferred from
      Milesiinae to Syrphinae.

PMID- 18726368
TI  - The function of a regulatory gene, scrX related to differentiation in
      Streptomyces coelicolor.
AB  - A new gene, scrX from Streptomyces coelicolor was cloned and sequenced. It
      consists of 660 base pair, encoding a peptide of 220 amino acids. There are three
      rare codons in scrX which are AAA, AAA and ATA. scrX gene may be a typical
      differentiation regulator which was strictly controlled at translational level.
      The comparison of amino acids also revealed that ScrX belonged to Ic1R family
      which acted in transcriptional regulation of prokaryote. Studies on gene function
      by gene disruption and complementation indicated that scrX may play a positive
      regulation role in spore formation of Streptomyces coelicolor.

PMID- 18726369
TI  - Using yeast two-hybrid system to detect interactions of ATP synthase subunits
      from Spinacia oleracea.
AB  - Subunit interactions among the chloroplast ATP synthase subunits were studied
      using the yeast two-hybrid system. Various pairwise combinations of genes
      encoding alpha, beta, gamma, delta and epsilon subunits of Spinach ATP synthase
      fused to the binding domain or activation domain of GAL4 DNA were introduced into
      yeast and then expression of a reporter gene encoding beta-galactosidase was
      detected. Of all the combinations, that of gamma and epsilon subunit genes showed
      the highest level of reporter gene expression, while those of alpha and beta, a
      and epsilon, beta and epsilon and beta and delta induced stable and significant
      reporter gene expression. The combination of delta and epsilon as well as that of
      delta and gamma induced weak and unstable reporter gene expression. However,
      combinations of alpha and gamma, beta and gamma and alpha and delta did not
      induce reporter gene expression. These results suggested that specific and strong
      interactions between gamma and epsilon, alpha and beta, alpha and epsilon, beta
      and epsilon and beta and delta subunits, and weak and transient interactions
      between delta and epsilon and delta and gamma subunits occurred in the yeast cell
      in the two-hybrid system. These results give a new look into the structural
      change of ATP synthase during catalysis.

PMID- 18726370
TI  - Differential recognition of MHC class I molecules of xeno-/allo-endothelial cells
      by human NK cells.
AB  - Using human umbilical vein endothelial cells (HUVEC) and porcine aortic
      endothelial cells (PAEC) as target cells, human peripheral blood NK cells (PBNK)
      and NK92 cells as effector cells, the differential cytotoxicities of NK cells to
      allo- and xeno-endothelial cells were studied. The influence of MHC class I
      molecules on the cytotoxicity of human NK cells was assayed using acid treatment,
      and blockades of MHC class I antigens, CD94 and KIR (NKB1). The results indicated
      that the killing of PAEC by the two kinds of NK cells is higher than that of
      HUVEC. After acid treatment, the cytotoxicity of the two kinds of NK cells to
      PAEC and HUVEC is significantly enhanced, but the magnitude of the enhancement is
      different. The enhancement of NK killing to acid treated HUVEC is much greater
      than that to PAEC. Blockade of CD94 mAb did not alter the NK cytotoxicity, while
      blockade of NKB1 mAb enhanced the cytotoxicity of PBNK to HUVEC and PAEC by 95%
      and 29% respectively. The results above suggested that the differential
      recognition of MHC I molecules of xeno-endothelial cells by human NK cells could
      be the major reason for higher NK cytotoxicity to PAEC. KIR might be the primary
      molecule that transduced inhibitory signals when endothelial cells were injured
      by NK cells.

PMID- 18726371
TI  - Expression and regulation of mRNAs for insulin-like growth factor-I receptor and
      LH receptor in corpora lutea.
AB  - Relationship between insulin-like growth factor-I receptor (IGF-IR) and
      luteinizing hormone receptor (LHR) mRNA expression as well as their regulation
      was determined in rat corpora lutea (CL). In the CL of estrous cycle rat, LHR
      mRNA positive CL expressed high level of mRNA of IGF-IR. While the expression of
      LHR mRNA decreased on estrus, the CL still expressed relatively high level of IGF
      IR mRNA. In pseudopregnant rat CL, the expression level of LHR mRNA was low on
      day 1, the most intense signals were detected on day 8, the signals of LHR mRNA
      became undetectable on day 14. In contrast to LHR expression, the high level of
      IGF-IR mRNA was observed in pseudopregnant CL of day 1, and thereafter its
      signals were detected from day 2 to day 14. Pregnant rat CL expressed both LHR
      and IGF-IR mRNAs. IGF-I stimulated LHR expression in CL. PGF(2alpha) inhibited
      expression of IGF-IR and LHR. PGE(2) negated the inhibiting effects of
      PGF(2alpha). These data suggest that IGF-I may be involved in regulating CL
      function, and maintaining CL structure through changes in expression of its
      receptors. Inhibited expression of IGF-IR by PGF(2alpha) may be part of
      mechanisms for regression of CL.

PMID- 18726372
TI  - Recording of calcium transient and analysis of calcium removal mechanisms in
      cardiac myocytes from rats and ground squirrels.
AB  - With confocal microscopy, we recorded calcium transients and analyzed calcium
      removal rate at different temperatures in cardiac myocytes from the rat, a non
      hibernator, and the ground squirrel, a hibernator. The results showed a
      remarkable increase of the diastolic level of calcium transients in the rat but
      no detectable change in the ground squirrel. Calcium transient of the ground
      squirrel, compared with that of the rat at the same temperature, had a shorter
      duration and showed a faster calcium removal. As indicated by the pharmacological
      effect of cyclopiazonic acid, calcium uptake by sarcoplasmic reticulum (SR) was
      the major mechanism of calcium removal, and was faster in the ground squirrel
      than in the rat. Our results confirmed the essential role of SR in hypothermia
      tolerant adaptation, and negated the importance of Na-Ca exchange. We postulated
      the possibility to improve hypothermia-tolerance of the cardiac tissue of non
      hibernating mammals.

PMID- 18726373
TI  - Complete nucleotide sequence and genome organization of tobacco mosaic virus
      isolated from Vicia faba.
AB  - Based on reported TMV-U1 sequence, primers were designed and fragments covering
      the entire genome of TMV broad bean strain (TMV-B) were obtained with RT-PCR.
      These fragments were cloned and sequenced and the 5' and 3' end sequences of
      genome were confirmed with RACE. The complete sequence of TMV-B comprises 6 395
      nucleotides (nt) and four open reading frames, which correspond to 126 ku (1 116
      amino acids), 183 ku (1 616 amino acids), 30 ku (268 amino acids) and 17.5 ku
      proteins (159 amino acids). The complete nucleotide sequence of TMV-B is 99.4%
      identical to that of TMV-U1. The two virus isolates share the same sequence of
      5', 3' non-coding region and 17.5 K ORF, and 6, 1 and 3 amino acid changes are
      found in 126 K protein, 54 K protein and 30 K protein, respectively. The possible
      mechanism on the infection of TMV-B in Vicia faba is discussed.

PMID- 18726374
TI  - Preliminary investigation of sequence-independent DNA binding proteins in rat
      skeletal muscle sarcoplasmic reticulum and their function.
AB  - To observe the binding of plasmid DNA to non-nuclear DNA binding proteins in
      sarcoplasmic reticulum (SR) and the effects of this binding on SR function,
      sarcoplasmic reticulum proteins in rat skeletal muscle were isolated by
      differential centrifuge and sucrose density-gradient centrifuge. The results
      showed that there are two sequence-independent DNA binding proteins in SR
      proteins, the molecular weights of which are 83 and 58 ku, respectively. Ca(2+)
      uptake and release of SR were remarkably promoted by the binding of plasmid DNA
      to DNA binding proteins in SR, the mechanism is probably through increasing of
      Ca(2+)-ATPase activity in SR and changing of character of Ca(2+) release channel
      ryanodine receptors induced by the binding. These results suggest that there
      exist DNA binding proteins in SR and its binding to DNA may affect Ca(2+)
      transport of SR.

PMID- 18726375
TI  - Regulating role of acetylcholine and its antagonists in inward rectified K(+)
      channels from guard cell protoplasts of Vicia faba.
AB  - The inward rectified potassium current of Vicia faba guard cell protoplasts
      treated with acetylcholine (ACh) or the antagonists of its receptors were
      recorded by employing the patch clamp technique. The results show that ACh at
      lower concentrations increases the inward K(+) current, in contrast, ACh at
      higher concentrations inhibits it. Treated with d-Tubocurarine (d-Tub), an
      antagonist of the nicotine ACh receptor (nAChR) inhibits the inward K(+) current
      by 30%. Treated with atropine (Atr), an antagonist of the muscarine (Mus) ACh
      receptor (mAChR) also inhibits it by 36%. However, if guard cell protoplasts are
      treated with d-Tub and Atr together, the inward K(+) current is inhibited by 60% 
      75%. Tetraethylammonium chloride (TEA), a strong inhibitor of K(+) channels has
      no effect on the inward K(+) current regulated by ACh, suggesting that there are
      inward K(+) channels modulated by AChRs on the membrane of the guard cell
      protoplasts. These data demonstrate an ACh-regulated mechanism for stomatal
      movement.

PMID- 18726376
TI  - Temperature-dependence and conformational basis of inositol 1,4,5-trisphosphate
      receptor regulated by Ca(2+).
AB  - The inositol 1,4,5-trisphosphate (InsP(3)) receptor was purified from bovine
      cerebellum and reconstituted in liposomes composed of phosphatidylcholine (PC)
      and phosphatidylethanolamine (PE) (1:1) successfully. No effect of Ca(2+)
      concentration on [(3)H]-InsP(3) binding to unreconstituted InsP(3) receptor could
      be observed either at 4 degrees C or at 25 degrees C, whereas the effect of
      [Ca(2+)] on reconstituted InsP(3) receptor depended on the temperature. The
      Ca(2+) concentration outside the proteolipsome ([Ca(2+)](o)) had no detectable
      effect on InsP(3) binding to InsP(3) receptor at 4 degrees C. In contrast, with
      increase of [Ca(2+)](o) from 0 to 100 nmol/L at 25 degrees C, the InsP(3) binding
      activity increased gradually. Then the InsP(3) binding activity was decreased
      drastically at higher [Ca(2+)](o) and inhibited entirely at 50 mumol/L
      [Ca(2+)](o). Conformational studies on intrinsic fluorescence of the
      reconstituted InsP(3) receptor and its quenching by KI and HB indicated that the
      global conformation of reconstituted InsP(3) receptor could not be affected by
      [Ca(2+)](o) at 4 degrees C. While at 25 degrees C, the effects of 10 mumol/L
      [Ca(2+)](o) on global, membrane and cytoplasmic conformation of the reconstituted
      InsP(3) receptor were different significantly from that of 100 nmol/L
      [Ca(2+)](o).

PMID- 18726377
TI  - Human single chain antibody to vascular endothelial growth factor: gene cloning,
      high-level expression, affinity maturation and bioactivity.
AB  - Using antibody phage display technique, a human single chain antibody to vascular
      endothelial growth factor (VEGF) has been cloned. The antibody expression reached
      45% of the total bacterial proteins. The purification and refolding of the
      antibody were completed in one step by using gel filtration chromatograph. ELISA
      analysis showed that the antibody not only specifically bound to human VEGF, but
      also competitively inhibited VEGF reacting with its receptors. In order to raise
      the affinity of the single chain antibody, its heavy chain variable region was
      randomly mutated using error-prone PCR and an antibody mutant library was
      constructed, from which a mutant with higher affinity was screened out. The three
      dimensional structure and binding affinity of wild type and mutant antibody were
      compared. Our study provided a potential reagent for tumor angiogenic therapy and
      a significant model for antibody high-level expression and affinity maturation.

PMID- 18726378
TI  - Screening of proteins that interact with human thrombopoietin receptor c-Mpl
      using yeast two-hybrid system.
AB  - Thrombopoietin (TPO) is the major cytokine involved in platelet production and
      exerts its effects via the receptor c-Mpl. The yeast two-hybrid system has been
      used to screen the proteins interacting with c-Mpl. First, the cDNA fragment of c
      Mpl intracellular domain was cloned into two-hybrid vector pAS2, and the
      resulting plasmid is designated as pASMM. Then a human placenta cDNA library was
      screened using the pASMM as a target plasmid. Seven positive clones were isolated
      from 150 000 independent transformants. Sequence analysis of one of the positive
      clones demonstrates that a part of coding sequence of vimentin from 611 bp to 3'
      end and flanking non-translation region was obtained. Therefore, there is an
      interaction between vimentin and TPO receptor. The results suggest that
      cytoskeletal protein may play an important role in TPO signal transduction
      pathway.

PMID- 18726379
TI  - Isolation of a (+)- delta-cadinene synthase gene CAD1-A and analysis of its
      expression pattern in seedlings ofGossypium arboreum L.
AB  - The cotton sesquiterpene cyclase, (+)-delta-cadinene synthase, is encoded by a
      gene family, which can be divided into two subfamilies:CAD1-A and CAD1-C. The
      geneCAD1-A was isolated fromG. arboreum. In situ hybridization performed on seven
      day-old cotton seedlings localized transcripts of both the CAD1 -A and CAD1 -C
      mainly in lateral root primordium and apical ground meristem, vascular tissues of
      emerging lateral roots, and also in procambium and some subepidermal cells of the
      hypocotyl. The CAD1 -A promoter showed a similar tissue-specificity in transgenic
      tobacco plants. Histochemistry showed occurrence of sesquiterpene aldehydes in
      outer cells of the lateral root tips, as well as in pigment glands. The CAD1 gene
      expression in G.arboreum seedlings and the spatial pattern of sesquiterpene
      biosynthesis constitute a chemical defense machinery in cotton seedlings.

PMID- 18726380
TI  - Cloning and characterization of the glutamate dehydrogenase gene inBacillus
      licheniformis.
AB  - ThegdhA genes of IRC-3 GDH(-)strain and IRC-8 GDH(+) strain were cloned, and they
      both successfully complemented the nutritional lesion of anE. coli glutamate
      auxotroph, Q100 GDH(-). However, thegdhA gene from the mutant IRC-8 GDH(+) strain
      failed to complement the glutamate deficiency of the wild type strain IRC-3.
      ThegdhA genes of the wild type and mutant origin were sequenced separately. No
      nucleotide difference was detected between them. Further investigations indicated
      that thegdhA genes were actively expressed in both the wild type and the mutant.
      Additionally, no GDH inhibitor was found in the wild type strain IRC-3. It is
      thus proposed that the inactivity of GDH in wild type is the result of the
      deficiency at the post-translational level of thegdhA expression. Examination of
      the deduced amino acid sequence ofBacillus licheniformis GDH revealed the
      presence of the motifs characteristic of the family I-type hexameric protein,
      while the GDH ofBacillus subtilis belongs to family II.

PMID- 18726381
TI  - Sequence analysis of keratin-like proteins and cloning of intermediate filament
      like cDNA from higher plant cells.
AB  - Two keratin-like proteins of 64 and 55 ku were purified from suspension cells
      ofDaucus carota L., and their partial amino acid sequences were determined. The
      homological analysis showed that the sequence from the 64 ku protein was highly
      homological to beta-glucosidase, and that from the 55 ku protein had no
      significant homologue in GenBank. Using conservative sequence of animal IF
      proteins as primer, we cloned a cDNA fragment fromDaucus carota L. Southern blot
      and Northern blot results indicated that this cDNA fragment was a single copy
      gene and expressed both in suspension cells and leaves. Homological analysis
      revealed that it had moderate homology to a variety of alpha-helical proteins.
      Our results might shed more light on molecular characterization of IF existence
      in higher plant.

PMID- 18726382
TI  - Expression and regulation of mRNAs for insulin-like growth factor (IGF-I), IGF
      binding protein-2, and LH receptor in the process of follicular atresia.
AB  - Expression of mRNAs for IGF-I, IGF-binding protein-2 (IGFBP-2), and LH receptor
      (LHR) as well as their regulations during induced follicular atresia was
      determined. 26-day-old female rats received 15 IU pregnant mare serum
      gonadotropins (PMSG). Through detection, it was demonstrated that apoptosis
      occurred in some small antral follicles after 48 h of PMSG treatment. At 96 h,
      apoptosis occurred in preovulatory follicles. At 120 h, numerous apoptotic cells
      appeared in preovulatory follicles. IGF-I was mainly expressed in preantral and
      small antral follicles from 48 to 120 h. At 48 and 96 h, the theca cells of
      preantral and antral follicles expressed high level of IGFBP-2 mRNA. At 48 h,
      there were strong signals of LHR mRNA in granulosa cells, but the LHR signals in
      granulosa cells significantly decreased at 96 and 120 h (p<0.001). Both epidermal
      growth factor (EGF) and IGF-I inhibited apoptosis in preantral and antral
      follicles. Meanwhile, it was observed that EGF promoted IGF-I mRNA expression,
      and in preovulatory follicles, IGF-I stimulated LHR mRNA expression. These
      results show that the interaction between ECF and IGF-I may be involved in the
      regulation of atresia of follicles at different stages of development.

PMID- 18726383
TI  - Gamma-aminobutyric acid and GABA(A) receptors are involved in directional
      selectivity of pretectal neurons in pigeons.
AB  - The present study describes the effects of gamma-aminobutyric acid (GABA) and its
      antagonists, bicuculline and 2-hydroxysaclofen, on visual responses of neurons in
      the pigeon nucleus lentiformis mesencephali (nLM). The results indicate that GABA
      significantly reduces both spontaneous activity and visual responsiveness, and
      GABA(A) antagonist bicuculline but not GABA(B) antagonist 2-hydroxysaclofen
      enhances visual responses of nLM cells examined. Furthermore, inhibition produced
      by motion in the null-direction of pretectal neurons is diminished by bicuculline
      but not by 2-hydroxysaclofen. It is therefore concluded that the null-direction
      inhibition of directional cells in the pigeon nLM is predominantly mediated by
      GABA and GABA(A) receptors. This inhibition may at least in part underlie
      directional asymmetry of optokinetic responses.

PMID- 18726384
TI  - Molecular replacement studies on crystal structure of allophycocyanin from red
      algaePorphyra yezoensis.
AB  - Using the crystal structure of allophycocyanin from cyanobacteriumSpirulina
      platensis (APC-SP) as a search model, the crystal structure of allophycocyanin
      from red algaePorphyra yezoensis (APC-PY) has been studied by molecular
      replacement methods. The APC-PY crystals (Form 3) belong to the space group of
      R32, cell dimensions a =b = 10.53 nm,c = 18.94 nm, alpha= beta = 90 degrees ,
      gamma= 120 degrees ; there is one alphabeta monomer in each crystallographic
      asymmetric unit in the cell. The translation function search gave a unique peak
      with a correlation coefficient (Cc) of 67.0% and an R-factor of 36.1 % for
      reflection data from 1.0 to 0.4 nm. Using the results by molecular replacement,
      the initial model of APC-PY was built, and the coincidence of the chromophore in
      APC-PY initial model with its2F (o)- F(c) OMIT map further confirms the results
      by molecular replacement.

PMID- 18726385
TI  - The role of hepatitis B virus x gene in development of primary hepatocellular
      carcinoma.
AB  - Primary hepatocellular carcinoma (HCC) is one of the most common cancers
      occurring in human, and there is strong epidemiological evidence suggesting that
      persistent hepatitis B virus (HBV) infection is the most important risk factor
      for its development.HBx gene was found to be a transactivator recently. Its
      continuous expression in hepatocytes may transactivate cellular genes which can
      play a certain role in development of HCC. TheHBx gene fragment was used to
      construct a recombinant eukaryotic expression vector pCEP4 and introduced into
      HepG2 cells. The effect ofHBx gene on HCC cells growth and its molecular
      mechanism in HCC cells regulation were investigated.

PMID- 18726386
TI  - Structures of nucleolus and transcription sites of rRNA genes in rat liver cells.
AB  - We observed the ultrastructure of nucleolus in rat liver cells by conventional
      electron microscopy, and employed cytochemistry NAMA-Ur DNA specific stain method
      to analyze the distribution and position of nucleolar DNAin situ. The results
      showed that nucleolar DNA of rat liver cells comes from nucleolus-associated
      chromatin, and continuously extends in the dense fibrillar component (DFC) of
      nucleolus, localizes at the periphery of fibrillar center (FC) and in DFC.
      Furthermore, by employing anti-DNA/RNA hybrid antibodies, we directly and
      selectively labeled transcription sites of rRNA genes and testified that
      localization of transcription sites not only to DFC but also to the periphery of
      FC.

PMID- 18726387
TI  - Isolation and characterization of a human apoptosis-inducing gene with yeast two
      hybrid system.
AB  - asy gene is a novel apoptosis-inducing gene, but its mechanism is unclear. To
      investigate the mechanism ofasy inducing apoptosis, a novel gene encoding ASY
      interacting protein (asyip) is isolated from human lung cell line (WI-38) cDNA
      library with yeast two-hybrid system. Theasyip gene is constitutively expressed
      as two mRNA transcripts with the size of 1.8 and 2.7 kb in various human tissues
      at different levels. Sequence analysis of full-length cDNA reveals that the two
      alternative transcripts ofasyip gene contain common 5' end and different 3' end,
      and share a common open reading frame encoding a polypeptide of 236 amino acids.
      Two protein kinase C phosphorylation sites and two casein kinase II
      phosphorylation sites are found in ASYIP amino acid sequence. Two highly
      hydrophobic regions encoding potentially two transmembrane domains are present.
      The ASYIP protein contains a C-terminal endoplasmic reticulum retrieval signal
      (Lys-Lys-Lys-Ala-Glu). Immunoprecipitation assay confirmed the interaction of ASY
      and ASYIP in mammalian cells. Compared withasy gene, overexpression ofasyip gene
      can inhibit growth of tumor cell Saos2 and induce cell apoptosis with a low
      efficiency.

PMID- 18726388
TI  - Cloning and structural and expressional characterization of BcpLH gene
      preferentially expressed in folding leaf of Chinese cabbage.
AB  - Vegetative growth of Chinese cabbage undergoes the four successive stages which
      are characterized with the definite types of juvenile, rosette, folding and head
      leaves. From shoot tips of Chinese cabbage at early folding stage, we constructed
      a cDNA library and screened the differentially expressed cDNA clones using the
      cDNAs derived from developing folding leaves and rosette leaves as probes. One
      complete length of cDNA clone is designated asBcpLH. Computer alignment matched
      BcpLH to the domains of double-stranded RNA binding (DBRM) and the homologous
      regions were recognized between BcpLH and human and mouse double-stranded RNA
      binding protein TRBP. PCR expression analysis shows that during vegetative
      growthBcpLH gene was expressed preferentially in folding leaves at folding stage.
      Transcripts ofBcpLH gene were increased when plants were sprayed with IAA. It is
      deduced thatBcpLH gene may be related to initiation of folding leaf and leafy
      head and induced by auxin in the aspect of transcriptional expression.

PMID- 18726389
TI  - Effect of phosphatidylglycerol on conformation and micro-environment of tyrosyl
      residue in photosystem II.
AB  - The structural aspects in the interaction of phosphatidylglycerol (PG) with
      photosystem II (PSII), mainly the effect of PG on conformation and
      microenvironment of tyrosine residues of PSII proteins were studied by Fourier
      transform infrared (FTIR) spectroscopy. It was found that the binding of PG to
      PSII particle induces changes in the conformation and micropolarity of phenol
      ring in the tyrosine residues. In other words, the PG effect on the PSII results
      in blue shift of the stretch vibrational band in the phenol ring from 1620 to
      1500 cm(-1) with the enhancement of the absorbance intensity. Additionally, a new
      spectrum of hydrogen bond was also observed. The results imply that the hydrogen
      bond formation between the OH group of phenol and one of PG might cause changes
      in the structures of tyrosine residues in PSII proteins.

PMID- 18726390
TI  - Extracellular calmodulin: A polypeptide signal in plants?
AB  - Traditionally, calmodulin (CaM) was thought to be a multi-functional receptor for
      intracellular Ca(2+) signals. But in the last ten years, it was found that CaM
      also exists and acts extracellularly in animal and plant cells to regulate many
      important physiological functions. Laboratory studies by the authors showed that
      extracellular CaM in plant cells can stimulate the proliferation of suspension
      cultured cell and protoplast; regulate pollen germination and pollen tube
      elongation, and stimulate the light-independent gene expression of Rubisco small
      subunit (rbcS). Furthermore, we defined the trans-membrane and intracellular
      signal transduction pathways for extracellular CaM by using a pollen system. The
      components in this pathway include heterotrimeric G-protein, phospholipase C,
      IP(3), calcium signal and protein phosphorylation etc. Based on our findings, we
      suggest that extracellular CaM is a polypeptide signal in plants. This idea
      strongly argues against the traditional concept that there is no intercellular
      polypeptide signal in plants.

PMID- 18726391
TI  - Expansion of CD34(+) cells from human umbilical cord blood by FL and/or TPO gene
      transfected human marrow stromal cell lines.
AB  - To elucidate the effect of gene transfected marrow stromal cell on expansion of
      human cord blood CD34(+) cells, a culture system was established in which FL and
      TPO genes were transfected into human stromal cell line HFCL. To establish gene
      transfected stromal cells co-culture system, cord blood CD34(+) cells were
      purified by using a magnetic beads sorting system. The number of all cells and
      the number of CD34(+) cells and CFC (CFU-GM and BFU-E) were counted in different
      culture systems. The results showed that in all 8 culture systems, SCF+IL-3+HFT
      manifested the most potent combination, with the number of total nucleated cells
      increasing by (893.3 +/-52.1)-fold, total progenitor cells (CFC) by (74.5 +/-5.2)
      fold and CD34(+) cells by 15.7-fold. Maximal expansions of CFC and CD34(+) cells
      were observed at the end of the second week of culture. Within 14 days of
      culture, (78.1 +/- 5.5)-fold and (57.0 +/- 19.7)-fold increases in CFU-GM and BFU
      E were obtained. Moreover, generation of LTC-IC from amplified CD34(+) cells
      within 28 days was found only in two combinations, i.e. SCF+IL-3+FL+TPO and
      SCF+IL-3+HFT, and there was no significant difference between these two groups
      statistically. These results suggest that human umbilical cord blood CD34(+)
      cells can be extensively expanded ex vivo by using gene transfected stromal cells
      along with cytokines.

PMID- 18726392
TI  - A neural network model on self-organizing emergence of simple-cell receptive
      field with orientation selectivity in visual cortex.
AB  - In order to probe into the self-organizing emergence of simple cell orientation
      selectivity, we tried to construct a neural network model that consists of LGN
      neurons and simple cells in visual cortex and obeys the Hebbian learning rule. We
      investigated the neural coding and representation of simple cells to a natural
      image by means of this model. The results show that the structures of their
      receptive fields are determined by the preferred orientation selectivity of
      simple cells. However, they are also decided by the emergence of self
      organization in the unsupervision learning process. This kind of orientation
      selectivity results from dynamic self-organization based on the interactions
      between LGN and cortex.

PMID- 18726393
TI  - Effect of lesion of nucleus robustus archistriatalis on call in bramble finch
      (Fringilla montifringilla).
AB  - The lesion of nucleus robustus archistriatalis (RA) has no effect on normal short
      calls in the bramble finch, but affects significantly the temporal and acoustic
      features of learned long calls. It causes the principal frequency of basic sound
      in monotone long calls to increase 500 cents, and to lose two upper partials. The
      lesion of RA not only results in the increased sound length of loud-sound and
      shortened coda of variable-tone long calls by 13.4%-22.1% and 21.2%-24.2% on
      average, respectively, but also makes the frequency rising coefficient (FRC) of
      even order partial tone in loud-sound drop 18.5%-25.8% on an average, and the
      step-up rate decrease 22.7% -24.0% on an average with the increase of
      frequencies. These results show that the control of temporal and frequency
      features of learned calls by RA matches to each other. Moreover, the lesion of
      bilateral RA can confuse the vocal pattern, and the produced long call has the
      character of both the mono- and variable-tone long calls. The prelude shows
      rising frequency, and the loud sound is monotone sound.

PMID- 18726394
TI  - Initial function analysis of a novel erythroid differentiation related gene
      EDRF1.
AB  - Erythroid differentiation depends on the establishment of specific patterns of
      gene expression. Hypersensitive site 2 (HS2, serving as a major enhancer of
      globin genes)-binding proteins may be involved in its natural open chromosomal
      environment formation. Previously we prepared monoclonal antibodies against HS2
      binding nuclear proteins of terminal differentiated erythroid cells. By utilizing
      the monoclonal antibodies, we screened lambda-gt11 human fetal liver cDNA
      expression library and obtained one cDNA clone, which was named erythroid
      differentiation related gene (EDRF1, Genbank accession number AF040247),
      encompassing an entire open reading frame. We investigated the expression pattern
      of EDRF1 by RT-PCR technique. And a clue to the function of EDRF1 has been found
      from confirmation of high levels of EDRF1 mRNA in differentiated K562 and human
      fetal liver tissue. To illuminate the function of EDRF1 in K562 cells, sense and
      antisense EDRF1 constructs were prepared and transfected into K562 cells. alpha
      globin mRNA was down-regulated and EpoR (erythropoietin receptor) mRNA expression
      was increased in antisense transfected cells. Cells transfected with sense
      construct grew more slowly than control cells suggested by [(3)H] thimidine
      incorporation experiments. Suppression of K562 proliferation was accompanied by
      increased spontaneous hemoglobin synthesis demonstrated by spectrometry. K562
      cells transfected with sense construct exhibited reduced clongenicity compared
      with control cells in methycellulose culture. These data provided the evidence
      that EDRF1 can influence globin expression and hemoglobin synthesis in K562 cells
      and modulated self-renewal in K562 cells.

PMID- 18726395
TI  - Screening of human vascular endothelial growth factor (VEGF) receptor Flt-1
      domain and study on its biological activity.
AB  - Four human vascular endothelial growth factor receptor Flt-1 cDNA fragments
      containing extracellular domain loops 2, 1-2, 2-3 and 1-3 respectively were
      amplified from human placental cDNA library by PCR and used for screening ligand
      binding domains by yeast two-hybrid system. The result showed that, not only loop
      1-3, but also the smaller fragment loop 2-3 could bind to hVEGF(165). Recombinant
      expression plasmids pPIC9K/Flt-1(1-3) and pPIC9K/Flt-1(2-3) were constructed and
      transformed to Pichia. pastoris host strain GS115, cultured in flasks, and
      expressed under the induction of 1% methanol. The expressed product existed in
      supernatant in the form of soluble molecules and contained more than 60% of total
      protein after being induced for 4d. After being purified by CM-Sepharose FF and
      Sephacryl S-100 chromatography, its purity reached above 90%. Biological assay in
      vitro showed that the binding capacity of expressed soluble Flt-1 (2-3) to
      hVEGF(165) and its inhibiting effect on the proliferation of human umbilical
      veins endothelial cells (HUVEC) stimulated with hVEGF(165) were close to those of
      sFlt-1(1-3). Animal test showed that sFlt-1(2-3) could inhibit the formation of
      regenerate blood vessels stimulated with hVEGF(165) significantly.

PMID- 18726396
TI  - Mediation of flowering by a calmodulin-dependent protein kinase.
AB  - A calmodulin-dependent protein kinase (MCK1) appeared important in regulating
      flowering in tobacco. The expression of modified MCK1 that lacks the C-terminal
      including calmodulin-binding domain upsets the flowering developmental program,
      leading to the abortion of flower primordia initiated on the main axis of the
      plant and, as well, caused the prolongation of the vegetative phase in axillary
      buds. The abortion process of flowers began first in the developing anthers and
      subsequently the entire flower senesces. In axillary buds the prolonged
      vegetative phase was characterized by atypical elongated, narrow, twisted leaves.
      These results suggested a role for calmodulin-dependent protein kinase homologs
      in mediating flowering.

PMID- 18726397
TI  - Directional tunings independent of orientation in the primary visual cortex of
      the cat.
AB  - A family of moving 'random-line' patterns was developed and used to study the
      directional tuning of 91 single units in cat primary visual cortex (V1). The
      results suggest that, in addition to the well-known orientation-dependent
      mechanism, there is also some kind of orientation-independent mechanism
      underlying the direction selectivity. The directional tuning of the neurons
      varies in accordance with the increase of orientation or non-orientation element
      in the stimulus.

PMID- 18726398
TI  - Influence of pigment substitution on the electrochemical properties of
      Rhodobacter sphaeroides 601 reaction centers.
AB  - With the help of pigment substitution, self-assembled monolayer film and square
      wave voltammetry, the influence of pigment substitution on the electrochemical
      properties of Rhodobacter sphaeroides 601 reaction centers was investigated.
      Results showed that the charge separation could also be driven by externally
      electric field, similar to the primary photochemical reaction in purple bacterial
      reaction center. On the surface of Au electrode, a self-assembled monolayer film
      (the RC-PDDA-DMSA film) was made up of 2,3-dimercaptosuccinic acid (DMSA), poly
      dimethyldiallylammonium chloride (PDDA) and reaction center (RC). When square
      wave voltammetry was used to study the RC-PDDA-DMSA film, four redox pairs in the
      photochemical reaction of RC were observed by changing frequency. With nonlinear
      fitting, the standard potential of P/P(+) and the corresponding electrode
      reaction rate constant were determined to be 0.522 V and 13.04 S(-1),
      respectively. It was found that the redox peak at -0.02 V changed greatly when
      bacteriopheophytin was substituted by plant pheophytin in the reaction center.
      Further studies indicated that this change resulted from the decrease in electron
      transfer rate between Bphe(-)/Bphe (Phe(-)/Phe) and Q(A) (-)/Q(A) after pigment
      substitution. After investigations of spectra and electrochemical properties of
      different RCs and comparisons of different function groups of pigments, it was
      indicated that the phytyl tail, similar to other substituted groups of
      pheophytin, affected the efficiencies of pigment substitution.

PMID- 18726399
TI  - Computational analysis and prediction for exons of PAC579 genomic sequence.
AB  - To isolate the novel genes related to human hepatocellular carcinoma (HCC), we
      sequenced P1-derived artificial chromosome PAC579 (D17S926 locus) mapped in the
      minimum LOH (loss of heterozygosity) deletion region of chromosome 17p13.3 in
      HCC. Four novel genes mapped in this genomic sequence area were isolated and
      cloned by wet-lab experiments, and the exons of these genes were located. 0-60 kb
      of this genomic sequence including the genes of interest was scanned with five
      different computational exon prediction programs as well as four splice site
      recognition programs. After analyzing and comparing the computationally predicted
      results with the wet-lab experiment results, some potential exons were predicted
      in the genomic sequence by using these programs.

PMID- 18726400
TI  - Differential expression and characterization analysis of a new gene with WD
      domains in fish oogenesis.
AB  - A new gene with WD domains is cloned and characterized according to its
      differential transcription and expression between previtellogenic oocytes (phase
      I oocytes) and fully-grown oocytes (phase V oocytes) from natural gynogenetic
      silver crucian carp (Carassius auratus gibelio) by using the combinative methods
      of suppressive subtraction hybridization, SMART cDNA synthesis and RACE-PCR. The
      full-length cDNA is 1870 bp. Its 5' untranslated region is 210 bp, followed by an
      open reading frame of 990 bp, which has the typical vertebrate initiator codon of
      ANNATG. The open reading frame encodes a protein with 329 amino acids. It has 670
      bp of 3' untranslated region and an AATAAA polyadenylation signal. Because it has
      92% homology to STRAP (serine-threonine kinase receptor-associated protein), a
      recently reported gene, we named it FSTRAP (fish STRAP). Virtual Northern
      blotting indicated that the FSTRAP was transcribed in fully-grown oocytes (phase
      V oocytes), but not in previtellogenic oocytes (phase I oocytes). RT-PCR analysis
      showed that FSTRAP was transcribed in brain, heart, kidney, muscle, ovary, spleen
      and testis, but not in liver. And its mRNA could be detected in the oocytes from
      phase II to phase V. Western blotting also showed that FSTRAP protein could be
      detected in brain, heart, kidney, muscle, ovary, spleen and testis except liver.
      Results of Western blotting on various oocytes were also similar to the RT-PCR
      data. FSTRAP protein was not expressed in the previtellogenic oocytes. Its
      expression initiated from phase II oocytes after vitellogenesis, and was
      consistent with the mRNA transcription.

PMID- 18726401
TI  - Molecular mechanism of effect of rotating constant magnetic field on organisms.
AB  - The effect of RCMF-magnetic therapy apparatus on signal substances was studied.
      The radioimmunoassay (RIA) suggested that the magnetic field increased beta
      endorphin markedly in plasma. ELISA indicated that the magnetic field inhibited
      vomiting reaction induced by chemotherapy drug, with reversible decrease of
      serotonin (5-HT) level in brains, small intestine tissue and serum. Furthermore,
      the bioeffect of magnetic fields on 5-HT level presented a typical window effect
      and post-effect, and the inhibitory effect of magnetic field on the emesis was
      parallel to the decrease level of 5-HT. This result implied that the decrease of
      5-HT might be the basis of rotating constant magnetic field (RCMF) inhibiting
      drug-induced emesis. The nitric acid reductase-spectrophotometry and nicotinamide
      adenine dinucleotide-diaphorase/arginine-vasopressin (AVP) cytochemistry
      technique showed that the magnetic field induced nitric oxide (NO) increase in
      hypothalamus and the high NO(A) level lasted for 3 hours. The results suggested
      that NO(A) increases after the treatment of the magnetic field in hypothalamus,
      which may result from strong expression of NO-ergic neuron in paraventricular
      hypothalamic nucleus (PVN), periventricular hypothalamic nucleus (PEN) and
      supraoptic nucleus (SON). The coexistence of NO and AVP may play an important
      role in the regulation of endocrine and neuroendocrine by the magnetic field. And
      our data also confirmed that the magnetic field increased the content of NO so
      strongly that high NO level lasted for 3 hours, also made neuropeptide Y (NPY)
      cell in medulla stained heavily.

PMID- 18726402
TI  - Y-chromosome haplotype distribution in Han Chinese populations and modern human
      origin in East Asians.
AB  - We investigated the distribution of Y-chromosome haplotype using 19 Y-SNPs in Han
      Chinese populations from 22 provinces of China. Our data indicate distinctive
      patterns of Y chromosome between southern and northern Han Chinese populations.
      The southern populations are much more polymorphic than northern populations. The
      latter has only a subset of the southern haplotypes. This result confirms the
      genetic difference observed between southern and northern ethnic populations in
      East Asia. It supports the hypothesis that the first settlement of modern humans
      of African origin occurred in the southern part of East Asia during the last Ice
      Age, and a northward migration led to the peopling of northern China.

PMID- 18726403
TI  - Secretion expression of recombinant glucagon inEscherichia coli.
AB  - A novel approach for the preparation of recombinant human glucagon was described.
      An expression vector pAGluT, containing phoA promoter, phoA signal peptide and
      glucagon gene, was constructed by means of genetic engineering.Escherichia coli
      strain YK537 was transformed with pAGluT. High-level secretory expression of
      recombinant human glucagon was achieved. The expression yield of recombinant
      human glucagon was found to be 80 mg/L, approximately 30% of the total proteins
      in supernatant. The biological activities and the physicochemical properties of
      the purified recombinant human glucagon were found to be the same as that of
      native glucagon. In addition, our results suggested that phoA expression system
      may be suitable for the expression of other small peptides.

PMID- 18726404
TI  - Photo-induced electron transfer between hypocrellins and nano-sized semiconductor
      CdS : -EPR study on the kinetics of photosensitized reduction in HA-CdS and HB
      CdS systems.
AB  - Both HA-CdS and HB-CdS (Hys-CdS, Hys represents HA, HB) complex systems were
      established according to the dynamics of heterogeneous electron-transfer
      process[Formula: see text]. In these systems, the electron transferring
      from(1)Hys* to conduction band of CdS is feasible. Determined from the
      fluorescence quenching, the apparent association constants (K(app)) between
      Hypocrellin A (HA), Hypocrellin B. (HB) and CdS sol. were about 940 (mol/L)(-1),
      934 (mol/L)(-1), respectively. Fluorescence lifetime measurements gave the rate
      constant for the electron transfer process from(1)HA*,(1)HB* into conduction band
      of CdS semiconductor as 5.16 x 10(9) s(-1), 5.10 x 10(9) s(-1), respectively.
      TEMPO (2,2,6,6-tetramethy-1-piperdinyloxy), a stable nitroxide radical, was used
      in the kinetic study of the reduction reaction taking place on the surface of a
      CdS colloidal semiconductor, kinetics equation of the reaction was determined
      with the electron paramagnetic resonance (EPR) method, and the reaction order of
      TEMPO is zero. When Hys were added, the rate of EPR increased greatly. By
      comparing rate constants, the Hys-CdS systems were revealed to be about 350 times
      more efficient than CdS sol. alone in the photoreduction of TEMPO under visible
      light. It suggests that Hys can be used as efficient sensitizers of a colloidal
      semiconductor in the application of solar energy.

PMID- 18726405
TI  - NBS-LRR resistance gene homologues in rice.
AB  - Twenty three DNA fragments with a size of about 520 bp have been cloned from rice
      genome by PCR amplification using primers designed according to the conserved
      region of most plant resistance (R) genes which have Nucleotide Binding Site
      (NBS) and Leucine-Rich Repeat (LRR) domains. Homologous comparison showed that
      these fragments contained typical motifs of the NBS-LRR resistance gene class,
      kinase 1a, kinase 2a, kinase 3a and domain 2. Thus they were named R gene
      homologous sequences (RS). These RS were divided into 4 groups by clustering
      analysis and mapped onto chromosomes 1, 3, 4, 7, 8, 9, 10 and 11, respectively,
      by genetic mapping. Ten RS were located in the chromosomal intervals where known
      R genes had been mapped. Further RFLP analysis of an RS, RS13, near the bacterial
      blight resistance geneXa4 locus on chromosome 11 among near isogenic lines and
      pyramiding lines ofXa4 showed that RS13 was possibly amplified from the gene
      family ofXa4.

PMID- 18726406
TI  - Recombination with coat protein transgene in a complementation system based
      onCucumber mosaic virus (CMV).
AB  - In order to study the feasibility ofCucumber mosaic virus (CMV) as an expression
      vector, the full-length cDNA of RNA 3 from strain SD was cloned and the sequence
      around the start codon of the coat protein (CP) gene was modified to create anNsi
      I site for insertion of foreign genes. The CP gene was replaced by the green
      fluorescent protein (GFP) gene. The cDNAs of Fny RNAs 1 and 2 and the chimeric SD
      RNA 3 were cloned between the modified 35S promoter and terminator. Tobacco
      protoplasts were transfected with a mixture of the viral cDNAs containing 35S
      promoter and terminator as a replacement vector and expressed GFP. A
      complementation system was established when the replacement vector was inoculated
      onto the transgenic tobacco plants expressing SD-CMV CP. GFP was detected in the
      inoculated leaves in 5 of 18 tested plants and in the first upper systemic leaf
      of one of the 5 plants ten days after inoculation. However, no GFP could be
      detected in all the plants one month after inoculation. Recombination between the
      CMV vector and the CP transgene was proved by retro-transcriptional polymerase
      chain reaction (RT-PCR) and verified by DNA sequencing. Our results argue against
      the feasibility of the CMV-based replacement vector trans-complemented by the CP
      transgene, and at the same time, enlighten ways to improve the CMV-based
      expression vector and the biosafety of CMV CP-mediated virus resistant transgenic
      plants.

PMID- 18726407
TI  - Selection and design of high affinity DNA ligands for mutant single-chain
      derivatives of the bacteriophage 434 repressor.
AB  - Single-chain repressor RR(Tres) is a derivative of bacteriophage 434 repressor,
      which contains covalently dimerized DNA-binding domains (amino acids 1-69) of the
      phage 434 repressor. In this single-chain molecule, the wild type domain R is
      connected to the mutant domain R(TRES) by a recombinant linker in a head-to-tail
      arrangement. The DNA-contacting amino acids of R(TRES) at the -1, 1, 2, and 5
      positions of the a3 helix are T, R, E, S respectively. By using a randomized DNA
      pool containing the central sequence -CATACAAGAAAGNNNNNNTTT-, a cyclic,in vitro
      DNA-binding site selection was performed. The selected population was cloned and
      the individual members were characterized by determining their binding affinities
      to RR(Tres) The results showed that the optimal operators contained the TTAC or
      TTCC sequences in the underlined positions as above, and that the Kd values were
      in the 1 x 10(-12) mol/L-1 x 10(11) mol/L concentration range. Since the affinity
      of the natural 434 repressor to its natural operator sites is in the 1 x 10(-9)
      mol/L range, the observed binding affinity increase is remarkable. It was also
      found that binding affinity was strongly affected by the flanking bases of the
      optimal tetramer binding sites, especially by the base at the 5' position. We
      constructed a new homodimeric single-chain repressor R(TRES)R(TRES) and its DNA
      binding specificity was tested by using a series of new operators designed
      according to the recognition properties previously determined for the R(TREs)
      domain. These operators containing the consensus sequenceGTAAGAAARNTTACN
      orGGAAGAAARNTTCCN (R is A or G) were recognized by R(TRES)R(TRES) specifically,
      and with high binding affinity. Thus, by using a combination of random selection
      and rational design principles, we have discovered novel, high affinity protein
      DNA interactions with new specificity. This method can potentially be used to
      obtain new binding specificity for other DNA-binding proteins.

PMID- 18726408
TI  - Study on the molecular basis of glucoamylase overproduction of a mutant
      strainAspergillus niger T21.
AB  - The molecular basis for increasing of the glucoamylase (GLA) production of
      anAspergillus niger mutant T21 was investigated. Northern blot analysis showed
      that the amount ofglaA specific mRNA ofA. niger T21 was about 20 times higher
      than that of its start strainA. niger AS 3.795. The twoglaA promoter fusions
      (PglaA)-uidAs were respectively introduced intoA. niger. Analysis of GUS activity
      of the transformants revealed that thePglaA activity of the strain T21 is about 3
      times stronger than that of the strain AS 3.795. It is considered to be one of
      the reasons for the increase ofglaA transcriptional level in the strain T21.
      However, comparing with the 20 times increase in the amount of glaA mRNA the
      alteration oftrans regulation should be the most important reason for that. The
      results of deletion analysis of 5'-c/s region ofA. niger T21glaA gene indicated
      that the region from-408 to-513 bp upstream of ATG is responsible for the high
      level expression ofglaA.

PMID- 18726409
TI  - Comparative study of symmetric and asymmetric somatic hybridization between
      common wheat andHaynaldia villosa.
AB  - Symmetric and asymmetric protoplast fusion between long term cell suspension
      derived protoplasts ofTriticum aestivum (cv. Jinan 177) and protoplasts
      ofHaynaldia villosa prepared from one-year-old embryogeneric calli was performed
      by PEG method. In asymmetric fusion, donor calli were treated with gamma ray at a
      dose of 40, 60, 80 Gy (1.3 Gy/min) respectively and then used to isolate
      protoplasts. Results of morphological, cytological, biochemical (isozyme) and 5S
      rDNA spacer sequence analysis revealed that we obtained somatic hybrid lines at
      high frequency from both symmetric and asymmetric fusion. Hybrid plants were
      recovered from symmetric and low dose gamma-fusion combinations. GISH (genomicin
      situ hybridization) analysis proved exactly the existence of both parental
      chromosomes and the common occurrence of several kinds of translocation between
      them in the hybrid clones regenerated from symmetric and asymmetric fusion. And
      the elimination of donor DNA in hybrid clones regenerated from asymmetric fusion
      combinations was found to increase with the increasing gamma doses. It is
      concluded that transference and recombination of nuclear DNA can be achieved
      effectively by symmetric and asymmetric fusion, hybrids with small fragment
      translocation which are valuable in plant breeding can be obtained directly by
      asymmetric fusion.

PMID- 18726410
TI  - Developmental stage-related expression and identification of murine erythroid
      differentiation-denucleation factor (MEDDF).
AB  - Using MEDDF cDNA fragment in plasmid pBS-SK-MEDDF as template the coding sequence
      was cloned into pGEM-T-Easy plasmid by PCR method to delete non-coding sequence.
      After DNA sequencing it was confirmed that the clone sequence was correct, the
      coding region then was inserted into the vector pET-30a betweenBamH I andHind III
      to construct eukaryotic expression vector. It was found that the specific protein
      was up to 40% of total bactorial proteins in certain high-expressionE. coli. High
      titer of anti-sera was detected by inoculating New Zealand rabbits with purified
      MEDDF protein as an antigen. By using immunocytochemical staining it was
      demonstrated that the expression of MEDDF was exhibited in a developmental stage
      specific manner, suggesting that MEDDF may play a certain role in the initiation
      of murine erythroid terminal differentiation and nuclear condensation. As for the
      expression of MEDDF appearing in granulocytes and megakaryocyter in murine bone
      marrow, it may indicate that there is an original relationship between the
      proteins and differentiation of murine myelogenous lineage.

PMID- 18726411
TI  - Molecular cloning and identification of naturally occurring human
      antisenseangiopoietin-1: Gna-1.
AB  - One novel cDNA fragment was obtained from vascular endothelial cells by
      differential display reverse transcription PCR technique. By using this fragment
      as probe, we screened the human artery cDNA library and obtained one cDNA clone
      which is 2198 bp in length. After sequencing and homology researching, we found
      that the clone contained a region of 851 bp in length complementary to that of
      humanangiopoietin-1 cDNA, encoding the partial fibrinogen-like domain and 3' non
      translational region. It was inferred that this clone was a naturally occurring
      antisense RNA of humanangiopoietin-1, designated asGna-1. Gna-1 does not encode
      protein. The transcription ofGna-1 in human umbilical vein endothelial cells and
      ECV304 cells was confirmed by RT-PCR method.Gna-1 may be involved in regulating
      the function ofangiopoietin-1, and play a significant role in angiogenesis.

PMID- 18726412
TI  - Paternal inheritance of mitochondrial DNA in the sheep (Ovine aries).
AB  - Paternal inheritance of mitochondria DNA in sheep was discovered by examination
      of 152 sheep from 38 hybrid families for mtDNA D-loop polymorphisms using PCR
      RFLP, amplification of repeated sequence somain, and PCR-SSCP of the D-loop 5'
      end region of a 253 bp fragment. Our findings have provided the first evidence of
      paternal inheritance of mtDNA in sheep and possible mechanisms of paternal
      inheritance were discussed.

PMID- 18726413
TI  - Importance of over-dominance as the genetic basis of heterosis in rice.
AB  - In populations derived from commercial hybrid rice combination Shanyou 10, F(1)
      heterosis and F(2) inbreeding depression were observed on grain yield (GYD) and
      number of panicles (NP). Using marker loci evenly distributed on the linkage map
      as fixing factors, the F(2) population was divided into sub-populations. In a
      large number of sub-populations, significant correlations were observed between
      heterozygosity and GYD, and between heterozygosity and NP. This was especially
      true in type III sub-populations in which the genotype of a fixing factor was
      heterozygotes. In type III sub-populations, 15 QTL for GYD and 13 QTL for NP were
      detected, of which the majority exhibited over-dominance effects for increasing
      the trait values. This study showed that over-dominance played an important role
      in the genetic control of heterosis in rice.

PMID- 18726414
TI  - Purification, crystallization and preliminary crystallographic investigations of
      selenium-containing phycocyanin from selenium-rich algae (Spirulina platensis).
AB  - The selenium-containing phycocyanin from the selenium-rich algae (Spirulina
      platensis) has been crystallized in two crystal forms by the hanging-drop vapor
      diffusion techniques. A chromatographic procedure of gel filtration and anion
      exchange was used for purification. Form I crystal with space group P2(1) and
      cell parameters a =108.0 A, b= 117.0 A, c = 184.0 A, beta= 90.2 degrees and
      12(alphabeta) units in the asymmetric unit was obtained by using (NH(4))(2)SO(4)
      as precipitant. These crystals diffract up to 2.8 A. Form II crystal obtained by
      using PEG4000 as precipitant belongs to space group P6(3) with unit cell
      constants a = 155.0 A, c = 40.3 A, gamma =120.0 degrees and one(alphabeta) unit
      in the asymmetric unit. The crystals diffract beyond 2.9 A. The possible stacking
      forms of phycocyanin molecules in the first crystal form were discussed.

PMID- 18726415
TI  - GABA/progesterone-induced polyphosphoinositide (PPI) breakdown and its role in
      the acrosome reaction of guinea pig spermatozoa in vitro.
AB  - To investigate whether GABA/progesterone (P(4)) stimulates PPI breakdown and its
      role in the acrosome reaction (AR), spermatozoa of guinea pig were preincubated
      in MCM-LCa(2+) for 5.5 h and then labeled with [(32)P]pi for 1 h. Samples were
      washed through a three-step gradient Percoll, adjusted to 5x10(7) cells/mL and
      exposed to 2 mmol/L Ca(2+), 5 micromol/L GABA, 10 micromol/L P(4) and other
      agents. Lipids were separated by t.l.c. and radioactivity in spots determined by
      scintillation counting. The AR was assessed by phase-contrast microscopy. The
      results showed that (i) when spermatozoa were treated with GABA,(32)P-label
      diminished rapidly in phosphatidylinositol 4, 5-bisphosphate (PIP(2)),
      phosphatidylinositol 4-phosphate (PIP), and increased in phosphatidic acid (PA).
      The loss of label from PPI was almost completed by 10 min. The time-course of the
      AR was much slower than PPI when spermatozoa reached a maximal response by 15
      min; (ii) the pattern of PPI hydrolysis and stimulation of AR was similar for the
      three agonists tested; their potency followed the order A23187>progesterone> or
      =GABA; (iii) GABA-induced PIP(2) hydrolysis and rise in PA and the AR were
      prevented by inclusion of 10 mmol/L neomycin; (iv) the loss of PIP(2) labeling
      and the increase in PA labeling abolished when spermatozoa were exposed to EGTA
      or Ca(2+) channel blocker. These results indicate that GABA or P(4)-induced PPI
      breakdown is an important and essential event in the series of changes to
      membrane fusion during the AR of guinea pig spermatozoa and this effect is
      mediated via calcium by activation of phosphatidylinositol-specific phospholipase
      C.

PMID- 18726416
TI  - Expression of cytochrome P4502E1 in human liver: Relationship between genotype
      and phenotype in Chinese.
AB  - Polymorphic cytochrome P4502E1 (CYP2E1) plays an important role in the metabolic
      activation of many carcinogens. We have previously shown that the c1/c1 genotype
      recognized by Rsa I in the 5'-regulatory region of the CYP2E1 may be a
      susceptibility factor for developing esophageal cancer and lung cancer in
      Chinese. The present study was to investigate the relationship between the Rsa I
      genotype and the expression of CYP2E1 in human livers. A total of 50 liver
      specimens were genotyped for CYP2E1 and assayed for CYP2E1 protein contents and
      functional activity by using specific antibody in immunoblot and a probe
      substrate,p-nitrophenol. A considerable interindividual variation in CYP2E1
      protein (20-fold) and functional activity (56-fold) was observed among these
      liver samples. However, when they were categorized according to genotype, the
      mean content of CYP2E1 protein was significantly higher among individuals with
      the c1/c1 genotype than that among those having c1/c2 or c2/c2 genotype [124.0+/
      83.9 pmol/mg (n = 28) versus 65.5 +/-38.9 pmol/mg (n = 22),P<0.01]. The mean
      activity of CYP2E1 towards p-nitrophenol for the c1/c1 genotype was also higher
      than that for the variant genotypes (198.4+/-27.8 pmol/min/mg versus 101.2 +/
      18.1 pmol(-1) . min(-1) . mg(-1),P<0.01). Also, the protein levels and functional
      activity showed a significant correlation (r = 0.68,P<0.01). These results
      demonstrate an association between the Rsa I genotype and the phenotype of CYP2E1
      in our samples, and the data are compatible with the assumption that CYP2E1 c1/c1
      genotype is a susceptibility factor for certain cancers in Chinese.

PMID- 18726417
TI  - Resistance of SKW6 cell to apoptosis induction with anti-Fas antibody upon
      transduction of a reverse fragment to a cDNA encoding human 6A8 alpha
      mannosidase.
AB  - The effect of transduction with a reverse fragment to a cDNA encoding human 6A8
      alpha-mannosidase on apoptosis induction of human B cell line SKW6 by anti-Fas
      antibody was tested. Apoptosis-inducer of anti-Fas monoclonal antibody was used
      to induce apoptosis in SKW6 cells. Giemsa's staining, Annexin-V-FLUOS staining
      and DNA ladder test were used to determine the events of apoptosis. Indirect
      immunofluorescent staining with anti-Fas antibody was performed to detect the
      surface Fas expression. In a time-course test of 12, 24 and 36 h for apoptosis
      induction by anti-Fas antibody, DNA ladder was observed in the wild-type SKW6
      cells in a time-dependent fashion. Mock transduction had no effect on DNA ladder
      production. However, no DNA ladder was detected in the rAAV-antisense 6A8 cDNA
      transduced SKW6. Results from Annexin-V-FLUOS staining on anti-Fas antibody
      treated cells revealed that the staining-positive rate in the rAAV-antisense 6A8
      cDNA-transduced SKW6 cells was decreased in comparison to that in the wild-type
      and the mock-transduced cells. Giemsa's staining observation showed that the
      number of dying (with apoptotic bodies) and dead cells was reduced in the rAAV
      antisense 6A8 cDNA-transduced SKW6 cells in comparison with that in the wild-type
      and the mock-transduced cells upon anti-Fas antibody induction. The transduction
      did not affect the expression of Fas molecular on cell surface. 100% cells in all
      the groups showed Fas expression. The SKW6 cells became resistant to apoptosis
      induction by anti-Fas antibody upon transduction with a reverse fragment to a
      cDNA encoding human 6A8 alpha-mannosidase. The transduction did not affect the
      expression of Fas molecule on cells.

PMID- 18726418
TI  - Differential modulation by AMPA of signals from red- and green-sensitive cones in
      carp retinal luminosity-type horizontal cells.
AB  - Intracellular recordings were made from luminosity-type horizontal cells (LHCs)
      in the isolated superfused carp retina and the effect of AMPA (alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid), a glutamate receptor agonist, on
      these cells was studied. AMPA suppressed the responses of LHCs driven by red
      sensitive (R-) cones whereas it potentiated the responses driven by green
      sensitive (G-) cones. The AMPA effect could be completely blocked by GYKI 53655,
      a specific AMPA receptor antagonist, indicating the exclusive involvement of AMPA
      preferring receptors. The AMPA effect persisted in the presence of picrotoxin
      (PTX) or dihydrokainic acid (DHK), suggesting that the feedback from LHCs onto
      cones and glutamate transporters on cones may not be involved. It is suggested
      that there may exist different AMPA receptor subtypes with distinct
      characteristics on LHCs, which mediate signal transfer from R-and G-cones to
      LHCs, respectively.

PMID- 18726419
TI  - Simultaneous multi-parameter observation of Harringtonine-treating HL-60 cells
      with both two-photon and confocal laser scanning microscopy.
AB  - Harringtonine (HT), a kind of anticancer drug isolated from Chinese herb
      Cephalotaxus hainanensis Li, can induce apoptosis in promyelocytic leukemia HL-60
      cells. With both two-photon laser scanning microscopy and confocal laser scanning
      microscopy in combination with the fluorescent probe Hoechst 33342,
      tetramethyrhodamine ethyl ester (TMRE) and Fluo 3-AM, we simultaneously observed
      HT-induced changes in nuclear morphology, mitochondrial membrane potential and
      intracellular calcium concentration ([Ca(2+)](i)) in HL-60 cells, and developed a
      real-time, sensitive and invasive method for simultaneous multi-parameter
      observation of drug-treating living cells at the level of single cell.

PMID- 18726420
TI  - Preliminarily functional analysis of a cloned novel human gene ADAM29.
AB  - ADAM is a family of type I integral membrane proteins which are characterized by
      sharing a disintegrin and metalloprotease domain and involved in many important
      physiological processes such as fertilization, neurogenesis and inflammatory
      response. A novel human ADAM gene-ADAM29, which was cloned in our laboratory, is
      exclusively expressed in human testis and contains a potential fusion domain. A
      full-length cDNA of ADAM29 was obtained by using multiple-step PCR. Phylogenetic
      tree of known mammalian ADAMs specifically expressed in testis was reconstructed.
      Polyclonal antiserum was raised by immunizing the rabbits with sub-peptide of
      ADAM29 (Leu268-Asp374) as immunogen. The result of immunohistochemical test on
      human testis showed that ADAM29 is expressed in different stages of
      spermatogenesis and in interstitial cells. ADAM29 may play a certain role in the
      signal transduction during the maturation of testis-associated cells.

PMID- 18726421
TI  - Isolation of pea matrix attachment region and study on its function in transgenic
      tobaccos.
AB  - A DNA fragment containing consensus sequence of matrix attachment region (MAR)
      has been isolated from pea genome. Compared with original DNA sequence, one 115
      bp-long repeat sequence is deleted in the obtained DNA sequence. DNA fragments
      located upstream and downstream of repeat DNA sequence respectively share 84% and
      93% homology to the corresponding original sequence, and contain A-box or T-box
      and TATAA sequence, which is characteristics short sequence of MARs. To test the
      function of the DNA sequence, the plant expression vectors in which beta
      glucuronidase gene (GUS, uidA) was used as reporter gene were constructed and
      transferred into tobaccos via Agrobacterium- mediated transformation procedure.
      Quantitative GUS assay showed that the average level of uidA expression was
      increased twofold for the presence of MAR, and the highest level of GUS activity
      of transgenic plants could be increased six times. The results cited above
      suggest that the isolated DNA sequence contains consensus sequence of MARs and
      has capability to increase expression level of gene in transgenic plants.

PMID- 18726422
TI  - Isolation and characterization of a new defense gene from soybean.
AB  - A cDNA clone of a single-copy gene designated SbPRP was isolated and
      characterized from 2-week-old soybean seedlings. It putatively encodes a
      bimodular protein similar to developmentally regulated proteins in other plant
      species. The deduced amino acid sequence consists of 126 amino acids with a
      distinct proline-rich domain (17 amino acids) and a long hydrophobically cysteine
      rich domain (84 amino acids), plus a signal peptide of 25 amino acids in N
      terminal. SbPRP mRNA transcripts accumulated in an organ specific manner. It can
      be detected in leaves and epicotyls of soybean seedlings, whereas virtually
      expression signal of SbPRP was not detected in cotyledons, hypocotyls and roots.
      Further Northern hybridization suggested that SbPRP steady-state mRNA level
      accumulated differentially not only in response to salicylic acid, but to the
      inoculation of soybean mosaic virus Sa strain. Also it was responsive to drought
      treatment and salt (NaCl) stress. Therefore it is likely that SbPRP functions as
      a defense gene in soybean.

PMID- 18726423
TI  - Cell biological mechanism for triggering of ABA accumulation under water stress
      in Vicia faba leaves.
AB  - Water stress-induced ABA accumulation is a cellular signaling process from water
      stress perception to activation of genes encoding key enzymes of ABA
      biosynthesis, of which the water stress-signal perception by cells or triggering
      mechanism of the ABA accumulation is the center in the whole process of ABA
      related-stress signaling in plants. The cell biological mechanism for triggering
      of ABA accumulation under water stress was studied in leaves of Vicia faba.
      Mannitol at 890 mmol * kg(-1) osmotic concentration induced an increase of more
      than 5 times in ABA concentration in detached leaf tissues, but the same
      concentration of mannitol only induced an increase of less than 40 % in ABA
      concentration in protoplasts. Like in detached leaf tissues, ABA concentration in
      isolated cells increased more than 10 times under the treatment of mannitol at
      890 mmol * kg(-1) concentration, suggesting that the interaction between
      plasmalemma and cell wall was essential to triggering of the water stress-induced
      ABA accumulation. Neither Ca(2+)-chelating agent EGTA nor Ca(2+)channel activator
      A23187 nor the two cytoskeleton inhibitors, colchicine and cytochalasin B, had
      any effect on water stress-induced ABA accumulation. Interestingly water stress
      induced ABA accumulation was effectively inhibited by a non-plasmalemma-permeable
      sulfhydryl-modifier PCMBS (p-chloromercuriphenyl-sulfonic acid), suggesting that
      plasmalemma protein(s) may be involved in the triggering of water stress-induced
      ABA accumulation, and the protein may contain sulfhydryl group at its function
      domain.

PMID- 18726424
TI  - Single nucleotide polymorphism analysis on chicken extracellular fatty acid
      binding protein gene and its associations with fattiness trait.
AB  - Fattiness is an important parameter to estimate meat quality, which has high
      heritability. In this experiment, F(2) chickens derived from Broilers crossing to
      Silky were used to study the effect of extracellular fatty acid binding protein
      (EX-FABP) gene on abdominal fat accumulation. 1.6 kb of the 5' region of the gene
      was amplified by six pairs of primers, and then single nucleotide polymorphisms
      (SNPs) were detected by the technique of single strand conformation polymorphism
      (SSCP) and then confirmed by sequencing. There were four nucleotides variations
      found, A-G at-1807, C-A at -1805, T-C at -1011 and a C insertion at -1000
      respectively. The result of least square analysis suggests that the birds with BB
      genotype defined by the second pair of primer have a higher abdominal fat weight
      and abdominal fat percentage than the birds with the other genotypes (AA and AB).
      It implied that EX-FABP gene could be a candidate locus or linked to a major gene
      to significantly affect abdominal fat traits in chicken.

PMID- 18726425
TI  - Change of cholinergic transmission and memory deficiency induced by injection of
      beta-amyloid protein into NBM of rats.
AB  - The change of cholinergic transmission of beta-amyloid protein (beta-AP) treated
      rats was studied by intracerebral microdialysis sampling combined with HPLC
      analysis. beta-AP(1-40) was injected into nucleus basalis magnocellularis (NBM).
      Passive avoidance response test (step-down test) and delayed alternation task
      were used for memory testing. The impairment of memory after injection of beta
      AP(1-40) into NBM exhibited mainly the deficiency of short-term working memory.
      One week after injection of beta-AP(1-40) the release of acetylcholine (ACh) from
      frontal cortex of freely-moving rats decreased significantly, and the response of
      cholinergic nerve ending to the action of high [K(+)] solution was rather weak.
      In control animals the percentage of increase of ACh-release during behavioral
      performance was 57%, while in beta-AP(1-40)-treated rats it was 34%. The
      temporary increase of the ACh-release of the rat put into a new place was also
      significantly diminished in beta-AP(1-40) -treated rats. The results show that
      the injection of beta-AP(1-40) into NBM impairs the cholinergic transmission in
      frontal cortex, and the impairment of cholinergic transmission may be the main
      cause of the deficit of working memory.

PMID- 18726426
TI  - Three-dimensional structure of the Chinese Sacbrood bee virus.
AB  - The RNA of Chinese Sacbrood Bee Virus (CSBV) was purified and used as template to
      obtain a 1096 bp cDNA fragment by RT-PCR amplification. This DNA fragment was
      cloned into pGEM-T Easy Vector for sequencing. Analyses of the sequenced CSBV RNA
      fragment revealed a nucleotide sequence homology of 87.6% and a deduced amino
      acid sequence homology of 94.6% with that of the Sacbrood Virus (SBV), indicating
      that CSBV is a different but highly homologous virus of SBV. The three
      dimensional (3D) structure of CSBV was determined at 2.5 nm resolution by using
      electron cryo-microscopy (cryoEM) and computer reconstruction methods. The 3-D
      structure showed that the capsid has aT = 1 (or P = 3) icosahedral capsid shell
      with a smooth surface. There were 12 pentons at its icosahedral vertices (5-fold
      axes) and 132 holes penetrating the shell. The 3-D structure also revealed
      densities corresponding to the CSBV genome, suggesting icosahedrally-ordered RNA
      organization, a novel feature not previously reported for any picornaviruses.

PMID- 18726427
TI  - Gene cloning, expression and purification of human mitochondrial tRNA(Leu(UUR))
      and its mutant.
AB  - Genes of human mitochondrial tRNA(Leu(UUR)) (mtRNA(Leu(UUR))) and its mutant
      (mtRNA(Leu(M))) were synthesized and inserted into the plasmid pGEM-9Zf(-)
      respectively.E.coli JM 109 was transformed by the recombinant plasmids containing
      the target genes. The mtRNA(Leu(UUR)) and mtRNA(Leu(M)) were expressed up to
      19.10% and 17.76% of total small RNA respectively. They were purified to 54%
      homogeneity by DEAE-sepharose-CL4B column chromatography and finally repurified
      by 15% PAGE/urea. Their kinetic parameters forE.coli LeuRS were measured. The
      results showed that the value of k(cal)/ K(m) of mtRNA(Leu(M)) was about one
      fifth of that of mtRNA(Leu(UUR)) and indicated the leucine acceptability of
      mtRNA(Leu(M)) was much lower than that of mtRNA(Leu(UUR)).

PMID- 18726428
TI  - Establishment of murine Smad5 double knockout ES cells and the studies on their
      properties.
AB  - Smad5 is an intracellular transducer of TGF-beta signals. Targeted disruption of
      murine Smad5 gene resulted in embryonic lethal. To study the function of Smad5 in
      organgenesis, we generated Smad5 double knockout ES cells by homologous
      recombination. We deleted the neo gene of the Smad5 targeted ES cells using Cre
      LoxP system. Smad5 double knockout ES cells were obtained by transfecting the
      targeted ES cells using the same targeting construct. The results of chimeric
      study showed that Smad5 might play an important role during the development of
      heart and neural tube.Smad5 double knockout ES cells formed teratoma when
      injected subcutaneously into nude mice. They differentiated into several types of
      cells, including neural cells, muscle cells, chondrocytes, endothelial cells and
      glandaceous cells. Smad5 double knockout ES cells are useful for studying the
      function of Smad5 mediated TGF-beta during the organgenesis and the in vitro
      differentiation of ES cells.

PMID- 18726429
TI  - Comparison on the genotoxic effects of nuclear vs cytoplasmic irradiation from
      the alteration of CD59 gene locus.
AB  - Using microbeam to irradiate human-hamster hybrid A(L) cells with defined number
      of a particles in a highly localized spatial region, this paper showed that
      cytoplasmic irradiation induced very little toxicity. For example, the cell
      killing by 4 a particle traversal through the cytoplasm was about 10%, and about
      70% cells survived after their cytoplasm was irradiated with 32 a particles. In
      contrast, the survival fractions for nuclear irradiation at the same doses were
      35% and less than 1% respectively. Mutation induction showed that while nuclear
      irradiation induced 3-4-fold more CD59 (-) mutants than cytoplasmic irradiation
      at equivalent particle traversal, at an equitoxic dose level of 90% survival, the
      latter exposure mode induced 3.3-fold more mutants than nuclear irradiation.
      Moreover, using multiplex PCR to analyze five marker genes on chromosome 11 (WT,
      CAT, PTH, APO-A1 and RAS), the results showed that the majority of mutants
      induced by cytoplasmic irradiation had retained all of the marker genes analyzed.
      By comparison, the proportion of mutants suffering loss of additional chromosomal
      markers increased with increasing number of particle traversal through nuclei.

PMID- 18726430
TI  - The responses to illusory contours of neurons in cortex areas 17 and 18 of the
      cats.
AB  - Responses to illusory contours (ICs) were sampled from neurons in cortical areas
      17 and 18 of the anesthetized cats. For ICs sensitive cells, the differences of
      receptive field properties were compared when ICs and real contour stimuli were
      applied. Two hundred orientation or direction selective cells were studied. We
      find that about 42 percent of these cells were the ICs sensitive cells. Although
      their orientation or direction tuning curves to ICs bar and real bars were
      similar, the response modes (especially latency and time course) were different.
      The cells' responses to ICs were independent of the spatial phases of sinusoidal
      gratings, which composed the ICs. The cells' optimal spatial frequency to
      composing gratings the ICs was much higher than the one to moving gratings.
      Therefore, these cells really responded to the ICs rather than the line ends of
      composing gratings. For some kinds of velocity-tuning cells, the optimal velocity
      to moving ICs bar was much lower than the optimal velocity to moving bars. The
      present results demonstrate that some cells in areas 17 and 18 of cats have the
      ability to respond to ICs and have different response properties of the receptive
      fields to ICs and luminance boundaries via different neural mechanisms.

PMID- 18726431
TI  - Cardiolipin is essential for higher proton translocation activity of
      reconstituted F(0).
AB  - The F(0) membrane domain of F(0)F(1)-ATPase complex had been purified from
      porcine heart mitochondria. SDS-PAGE with silver staining indicated that the
      purity of F(0) was about 85% and the sample contained no subunits of F(1)-ATPase.
      The purified F(0) was reconstituted into liposomes with different phospholipid
      composition, and the effect of CL (cardiolipin), PA (phosphatidic acid), PI
      (phosphatidylinositol) and PS (phosphatidylserine) on the H(+) translocation
      activity of F(0) was investigated. The results demonstrated that CL, PA and PI
      could promote the proton translocation of F(0) with the order of CLPA>PI, while
      PS inhibited it. Meanwhile ADM (adriamycin) severely impaired the proton
      translocation activity of F(0) vesicles containing CL, which suggested that CL's
      stimulation of the activity of reconstituted F(0) might correlate with its non
      bilayer propensity. After F(0) was incorporated into the liposomes containing PE
      (phosphatidylethanolamine), DOPE (dioleoylphosphatidylethanolamine) as well as
      DEPE (dielaidoylphosphatidylethanolamine), it was found that the proton
      translocation activity of F(0) vesicles increased with the increasing content of
      PE or DOPE, which has high propensity of forming non-bilayer structure, but was
      independent of DEPE. The dynamic quenching of the intrinsic fluorescence of
      tryptophan by HB (hypocrellin B) as well as fluorescent spectrum of acrylodan
      labeling F(0) at cysteine indicated that CL could induce F(0) to a suitable
      conformation resulting in higher proton translocation activity.

PMID- 18726432
TI  - Separation of a tungus producing taxol.
AB  - An endogenous filariform fungus has been separated from a tree named Taxus
      growing in the Aba region, Sichuan, China. The fungus is fermented in fluid
      medium for 3 weeks at 25 degrees C, then the HPLC and MALDI-TOF analysis of the
      zymotic fluid show that the zymotic fluid contains taxol. So it is a fungus which
      can produce taxol. It is named Taxomyces sp. temporarily.

PMID- 18726433
TI  - Expression pattern and functional analysis of a MADS-box gene M79 from rice.
AB  - Using a degenerated primer and a T-primer, a MADS-box gene, M79, was amplified by
      RT-PCR from rice fluorescence at meiosis stage and then cloned. Sequence analysis
      shows that M79 shares 98.2% homology with OsMADS7 at DNA level while only 92% at
      the amino acid level. The transcript of M79 possesses five different
      polyadenylation sites. Only a single copy of M79 gene has been found in rice
      genome, which is located on chromosome 8. M79 is expressed specifically in flower
      organs, from pre-meiosis stage through pollen maturation. Ectopic expression of
      M79 in T(0) and T(1) transgenic rice results in early-flowering, implying that
      M79 is involved in controlling the flowering time. In the same time, M79 may be
      involved in controlling the branching process to make more flower buds.

PMID- 18726434
TI  - Involvement of transcriptional enhancers in the regulation of developmental
      expression of yellow gene.
AB  - Upstream regulatory region and flanking DNA of yellow gene were isolated and
      cloned from a Drosophila genomic library. A vector containing yellow gene and
      regulatory elements was constructed using the recombinant DNA technique. Then
      this vector was integrated into Drosophila genome by genetic transformation.
      Using both FLP/FRT and Cre/LoxP site-specific recombination systems, two new
      yellow alleles were created at the same position in the genome of transgenic
      flies. Results from genetic and molecular analysis indicated that transcriptional
      enhancers regulate the developmental expression of the transgene. Furthermore,
      interactions between new-created yellow alleles were observed. Such interactions
      can influence markedly the expression of yellow gene during development. This
      effect may also be a form of enhancer-mediated gene expression.

PMID- 18726435
TI  - The complete genome of Enterovirus 71 China strain.
AB  - Five overlapping clones covering the full genome of Enterovirus 71 China strain
      SHZH98 were obtained and then the sequences were determined by the chain
      termination method. It showed that the full length of EV71 SHZH98 genome (not
      including Poly A tail) is 7408 bp. There are some diversities on the lengths and
      sequences of 5' UTR and 3' UTR between SHZH98 and the other EV71 strains. In P1
      capsid region, which is closely associated with viral immunogenicity, EV71 strain
      SHZH98 shares the highest homology with Taiwan strains; but in P2 and P3 non
      structural gene regions there are higher identities with Coxsakievirus A16 and
      EV71 strains MS, BrCr than with Taiwan strains. Phylogenetic tree constructed by
      structural gene region indicates that China strain SHZH98 has a closer
      relationship with Taiwan strains, however, in the non-coding region it has a
      closer relationship with Coxsakievirus A16, EV71 strains MS and BrCr. EV71 China
      strain was analyzed at the molecular level. The results will contribute to the
      basic study on enteroviruses and the EV71 prevention in China.

PMID- 18726436
TI  - Functional analysis of three amino acid residues of purR repressor, Trpl47, Gln
      218 and Gln-292 in Salmonella typhimurium.
AB  - The amber mutation sites of 6 purR(am) mutants were determined by cloning and DNA
      sequencing. The results showed that the mutations were distributed at three
      different sites in PurR coding region, G(721)(-->A), C(933)(-->T) and C(1155)(-
      >T), which respectively turn Trp-147, Gln-218 and Gln-292 of PurR into TAG
      terminal codon. To determine the effect of the three amino acid residues on
      regulatory function of PurR protein 5 different kinds of tRNA suppressor genes,
      Su3, Su4, Su6, Su7 and Su9 were used for creating the PurR protein variants with
      single amino acid substitution. The results indicated that Cys, Glu, Gly, His and
      Arg which substituted Trp-147 respectively all could not recover the regulation
      function of PurR. It confirmed that Trp-147 is a critical amino acid for the PurR
      function. Gln-292 substituted respectively by the same amino acids also could not
      recover the PurR function, demonstrating that Gln-292 is also an important amino
      acid residue in PurR.

PMID- 18726437
TI  - Three-dimensional structure of the inner core of rice dwarf virus.
AB  - Rice dwarf virus (RDV) is a double-shelled icosahedral virus. Using electron
      cryomicroscopy and computer reconstruction techniques, we have determined a 3.3
      nm resolution three-dimensional (3D) structure of the inner shell capsid without
      the outer shell and viral RNA. The results show that the inner shell is a thin,
      densely packed, smooth structure, which provides a scaffold for the full virus. A
      total of 120 copies of the major inner shell capsid protein P3 forms 60 dimers
      arranged in a T=1 icosahedral lattice. A close examination on the subunit packing
      of the T=1 inner core P3 with that of the T=13/ outer shell P8 indicated that P8
      trimers connect with P3 through completely non-equivalent, yet highly specific,
      intermolecular interactions.

PMID- 18726438
TI  - Initial hydrodynamic study on a new intraaortic axial flow pump: Dynamic aortic
      valve.
AB  - Rotary blood pumps have been researched as implantable ventricular assist devices
      for years. To further reduce the complex of implanted axial pumps, the authors
      proposed a new concept of intraaortic axial pump, termed previously as "dynamic
      aortic valve (DAV)". Instead of being driven by an intraaortic micro-electric
      motor, it was powered by a magnetic field from outside of body. To ensure the
      perfusion of coronary artery, the axial flow pump is to be implanted in the
      position of aortic valve. It could serve as either a blood pump or a mechanical
      valve depending on the power input. This research tested the feasibility of the
      new concept in model study. A column, made from permanent magnet, is jointed to
      an impeller in a concentric way to form a "rotor-impeller". Supported by a
      hanging shaft cantilevered in the center of a rigid cage, the rotor-impeller can
      be turned by the magnetic field in the surrounding space. In the present
      prototype, the rotor is 8 mm in diameter and 15 mm in length, the impeller has 3
      vanes with an outer diameter of 18 mm. The supporting cage is 22 mm in outer
      diameter and 20 mm in length. When tested, the DAV prototype is inserted into the
      tube of a mock circuit. The alternative magnetic field is produced by a rotating
      magnet placed side by side with the rotor-impeller at a distance of 30 mm. Once
      the alternative magnetic field is presented in the surrounding space, the DAV
      starts to turn, leading to a pressure difference and liquid flow in the tube. The
      flow rate or pressure difference is proportioned to rotary speed. At the maximal
      output of hydraulic power, the flow rate reached 5 L/min against an afterload of
      100 mmHg. The maximal pressure difference generated by DAV at a rotation rate of
      12600 r/min was 147 mmHg. The preliminary results demonstrated the feasibility of
      "DAV", further research on this concept is justifiable.

PMID- 18726439
TI  - Construction and immunogenicity prediction of Plasmodium falciparum CTL epitope
      minigene vaccine.
AB  - The minigenes encoding Plasmodium falciparum CTL epitopes restricted to human MHC
      class I molecular HLA-A2 and HLA-B51, which were both at high frequency among
      Chinese population, were constructed as mono-epitope CTL vaccines named
      pcDNA3.1/tr and pcDNA3.1/sh. The minigenes of the two epitopes were then tandem
      linked to form a dimeric CTL epitope minigene recombinant vaccine. After DNA
      transfection, the epitope minigenes were expressed respectively in two human cell
      lines, each bearing one MHC class I molecule named CIR/HLA-A2.1 and K562/HLA-B51.
      The intracellular expression of the CTL epitope minigenes not only enhanced the
      stability of HLA-A2.1 and HLA-B51 molecules but also increased the assemblage of
      MHC class I molecules on cell surfaces, which testified the specific process and
      presentation of those endogenous expressed epitopes. For the cells transfected
      with the dimeric minigene encoding two tandem linked epitopes, the expression and
      presentation of each epitope were also detected on cell membranes that bore
      different MHC class I molecules. It meant that the adjacency of the two CTL
      epitopes did not interfere with the specific process and presentation of each
      epitope. Compared with the ordinary CTL studies that inoculated synthesized
      epitope peptides with peripheral blood cells, this work aimed to process the
      epitopes directly inside HLA class I allele specific human cells, and thus
      theoretically imitated the same procedure in vivo. It was also an economical way
      to predict the immunogenicity of CTL epitopes at an early stage especially in
      laboratories with limited financial resource.

PMID- 18726440
TI  - Sequence analysis of a soil-borne wheat mosaic virus isolate from Italy shows
      that it is the same virus as European wheat mosaic virus and Soil-borne rye
      mosaic virus.
AB  - The complete sequence of the two RNAs of a furovirus isolate from durum wheat in
      Italy was determined. Sequence comparisons and phylogenetic analysis were done to
      compare the Italian virus with Soil-borne wheat mosaic virus (SBWMV) from the USA
      and with furovirus sequences recently published as European wheat mosaic virus
      (EWMV), from wheat in France, and Soil-borne rye mosaic virus (SBRMV), from rye
      and wheat in Germany. Over the entire genome, the Italian isolate RNA1 and RNA2
      had respectively 97.5% and 98.6% nucleotide identity with EWMV, 95.5% and 85.8%
      with SBRMV-G and 70.6% and 64.5% with SBWMV. The Italian isolate was therefore
      clearly distinct from SBWMV The European isolates all appear to belong to the
      same virus and the name Soil-borne cereal mosaic virus may resolve earlier
      ambiguities.

PMID- 18726462
TI  - Event-related potentials study on cross-modal discrimination of Chinese
      characters.
AB  - Event-related potentials (ERPs) were measured in 15 normal young subjects (18-22
      years old) using the "cross-modal and delayed response" paradigm, which is able
      to improve inattention purity. The stimuli consisted of written and spoken single
      Chinese characters. The presentation probability of standard stimuli was 82.5%
      and that of deviant stimuli was 17.5%. The attention components were obtained by
      subtracting the ERPs of inattention condition from those of attention condition.
      The results of the N1 scalp distribution demonstrated a cross-modal difference.
      This result is in contrast to studies with non-verbal as well as with English
      verbal stimuli. This probably reflected the brain mechanism feature of Chinese
      language processing. The processing location of attention was varied along with
      verbal/ non-verbal stimuli, auditory/visual modalities and standard/deviant
      stimuli, and thus it has plasticity. The early attention effects occurred before
      the exogenous components, and thus provided evidence supporting the early
      selective theory of attention. According to the relationship of N1 and Nd1, the
      present result supported the viewpoint that the N1 enhancement was caused by
      endogenous components overlapping with exogenous one rather than by pure
      exogenous component.

PMID- 18726463
TI  - Laser-induced tobacco protoplast fusion.
AB  - Laser tweezers can manipulate small particles, such as cells and organelles. When
      coupling them with laser microbeam selective fusion of two tobacco protoplasts
      containing some chloroplast was achieved. Physical and biological variables that
      affect laser trapping and laser-induced fusion were also discussed. The results
      show that the effect of chloroplast content and distribution on the yield of cell
      fusion is remarkable.

PMID- 18726464
TI  - CS3 fimbriae of enterotoxigenic Escherichia coli as chimeric expression carriers
      of heterologous antigenic determinants.
AB  - CS3 fimbriae, which are the strong immunogen, are produced by human
      enterotoxigenic Escherichia coli (ETEC). The possibility of using CS3 as a
      carrier of foreign antigenic determinants was investigated. A SacII site sequence
      was inserted into the structural gene of CS3 subunit by site-specific mutagenesis
      based on analyzing and predicting the properties of the proteins. A recombinant
      strain expressing CS3/CTP3 hybrid fimbriae was constructed by inserting the
      sequence encoding CTP3 into the SacII site created by directed mutagenesis in the
      structural gene of CS3 subunit and transforming the recombinant plasmid into the
      host of DH5alpha. The result of SDS-PAGE showed that the hybrid CS3/CTP3
      molecules were the fusion proteins with molecular masses of about 18.5 ku.
      Inoculating mice orally and intraperitoneally showed that both antibodies against
      CS3 and CTP3 were elicited. These results indicate that CS3 pili could be an
      exposure vector for heterologous antigenic determinants and become a powerful
      tool for the development of oral vaccines directed against mucosal pathogens.

PMID- 18726465
TI  - Investigation of various structures of DNA molecules (III) : Coil-globe
      transition of lambda-DNA induced by cationic surfactant.
AB  - The structure transition of lambda-DNA induced by cationic surfactant cellar
      media was investigated by using CD, SEM and AFM. The experimental data of CD
      revealed that lambda-DNA can be induced from B-form to a collapsed structure with
      the addition of the cationic surfactant CTAB to the system. The condensed process
      of lambda-DNA from coil state to small globular state (diameter about 1.25
      microm) and finally big globular state (diameter about 5.4 microm) was observed
      by using SEM and AFM.

PMID- 18726466
TI  - Immunolocation of antisperm monoclonal antibody 6B10 and corresponding antigen.
AB  - An antisperm monoclonal antibody 6B10 was produced by hybridoma technique of the
      isotype IgG. The monoclonal antibody was purified by means of ammonium sulfate
      precipitation and protein A-Sepharose C1-4B affinity chromatography. SDS
      polyacrylamide gel electrophoresis was used to evaluate the purity of the
      antibody. Evaluation of the sperm acrosomal status was determined by
      chlortetracycline (CTC) staining. It was found that monoclonal antibody 6B10 can
      inhibit the sperm acrosome reaction induced by progesterone. The corresponding
      antigen recognized by monoclonal antibody 6B10 was located on the plasma membrane
      of the sperm acrosome by indirect immunofluorescent microscopy and
      immunoelectronmicroscopy. Sperm protein was extracted by 1% Triton X-100. The
      molecular weight of the antigen is 50 ku, detected by Western blot. The antigen
      is a key protein in the sperm acrosome reaction and may be the receptor of
      progesterone on the sperm acrosome. It may either be developed as a candidate
      contraceptive vaccine or be used as a tool in pest/rodent management.

PMID- 18726467
TI  - Antigen changes of monoclonal antibody MSH27 in process of post-testicular
      maturation (in mice).
AB  - An anti-mouse spermatozoon monoclonal antibody, MSH27, as well as its purified
      antigen, can block sperm-egg membrane fusion. As a candidate protein for sperm
      egg membrane fusion, the sperm antigen was investigated in the process of post
      testicular maturation (PTM). The molecule was produced in testes and located on
      the plasma membrane of the postacrosomal area of the spermatozoon. However, the
      epitope recognized by the MSH27 (MSH27Ep) was not exposed until the occurrence of
      the acrosome reaction. In the process of fertilization, spermatozoa must complete
      the acrosome reaction before penetrating across the zona pellucidas (ZPs) to
      approach the plasma membrane of eggs. The effects of the acrosome reaction and
      penetration of the ZP on the exposure of the MSH27Ep were also studied. It was
      shown that the percentage of the spermatozoa with the MSH27Ep exposed increased
      followed with their mature status in PTM. In fact, it had a linear correlativity
      with the rate of the acrosome reaction. After spermatozoa had passed ZPs, almost
      all of them became the MSH27-positive in immuno-staining compared with only a
      part of the spermatozoa after the acrosome reaction. In a word, the exposure of
      MSH27Ep was coincident with attaining the ability to penetrate the plasma
      membrane of eggs.

PMID- 18726468
TI  - Theoretical study on primary reaction of photosynthetic bacteria.
AB  - Theoretical calculation was carried out on the primary electron donor P(870) of
      photosynthetic bacteria. The results show that: (i) the bimolecular structure of
      the primary electron donor is more advantageous in energy than monomolecular
      structure; (ii) the initial configuration of primary electron donor is no longer
      stable and changes to the configuration with lower energy and chemical reactivity
      after the charge separation. In the P(870), such structural change is completed
      through the rotation of C(3) acetyl, so the oxygen atom of acetyl interacts with
      the magnesium atom of another bacterio-chlorophyll molecule, and the total energy
      and chemical reactivity are reduced evidently. It is suggested that the
      structural change of the primary electron donor is important in preventing the
      occurrence of charge recombination during the primary reaction and maintaining
      the high efficiency of the conversion of sun-light to chemical energy. A new
      mechanism of primary reaction has been proposed, which can give reasonable
      explanations to the results of kinetic and site mutation studies.

PMID- 18726469
TI  - Amplification, analysis and chromosome mapping of novel homeobox-containing and
      homeobox-flanking sequences in rice.
AB  - Homeobox genes, widely distributed among animal and plant kingdoms, play an
      important role in developmental process. Several homeobox conserved fragments
      were amplified by PCR and the flanking regions were also obtained by an LM-PCR
      procedure. Sequencing and Southern analysis showed that they belong to a homeobox
      gene family of rice. Six homeobox-containing fragments were mapped on the
      molecular linkage map of rice. They were located on chromosomes 3, 4 and 7
      respectively. It is noteworthy that there are 4 homeobox fragments located on
      rice chromosome 3 and the result is also consistent with the comparative genomics
      between rice and maize.

PMID- 18726470
TI  - DNA immunization with fusion genes containing HCV core region and HBV core
      region.
AB  - The eucaryotic expression plasmids were constructed to express the complete
      (HCc191) or the truncated (HCc69 and HCc40) HCV core genes, solely or fused with
      the HBV core gene (HBc144). These constructions were transiently expressed in COS
      cells under the control of the CMV promoter. The antigenicity of HBc and HCc
      could be detected in the expression products by ELISA and Western blot. The mice
      immunized with these expression plasmids efficiently produced the anti-HCc
      antibodies, and also anti-HBc antibodies when the plasmids contained the fusion
      genes. In addition, the antibodies induced by the fusion genes were more
      persistent than those induced by the non-fusion HCV core genes. These indicate
      that the fusion of HCc genes to HBc gene is in favor of the immunogenicity of
      HCc, while the immunogenicity of HBc is not affected.

PMID- 18726471
TI  - Development and identification of wheat-Ag.pulcherrimum addition line and
      substitution line with BYDV resistance.
AB  - Breeding materials derived from CPI113500, amphidiploid of T. turgidum x
      Ag.pulcherrimum with barley yellow dwarf virus (BYDV) resistance, were evaluated
      by using BYDV resistance test, morphology observation, cytogenetics analysis,
      aneuploid analysis, isozyme electrophoresis, in situ hybridization. Two new
      germplasms resistant to BYDV were obtained. They were T.aestivum-Ag. pulcherrimum
      disomic addition line 96S16-11, and T. aestivum-Ag. pulcherrimum disomic
      substitution line 96W14-9.

PMID- 18726472
TI  - T7 RNA polymerase transcription of Escherichia coli isoacceptors tRNA(Leu).
AB  - The T7 promoter and the gene encoding tRNA(Leu) were synthesized chemically and
      cloned into plasmid pUC19, where the gene was transcribed in vitro with T7 RNA
      polymerase purified. It was found that spermidine had a negative effect on T7
      transcription. The amount of transcribed tRNA was about 250 times that of the
      template DNA under optimal reaction conditions. The unmodified tRNA(1) (Leu) and
      tRNA(2) (Leu) had similar leucine accepting ability, which however was only one
      fourth that of the native modified ones. This result indicated that the modified
      nucleotides of tRNA(Leu) played some though not key roles in its aminoacylation.

PMID- 18726473
TI  - Engineering human interferon alpha1c/86D with phage display technology.
AB  - Human interferon-alpha1c/86D (IFNalpha1c/86D) was functionally displayed on the
      surface of the filamentous bacteriophage using a phagemid vector system
      (pCANTAB5E). The key amino acid residues involved in the receptor binding were
      further defined with phage displayed 6-mer peptide library and two neutralizing
      antibodies against linear epitopes on the IFN-alpha1b, indicating that residues
      30, 33, 34, (AB-loop) and residues 124, 126, 127 (D helix, DE-loop) were more
      critical than the adjacent residues for recognition of receptor. In addition, a
      cassette mutagenesis library was generated by fully randomizing the sequence of
      the four positions 29, 31, 32 and 35 in AB-loop, and used to select phage-IFN
      variants with WISH-based panning method. Three phage-IFN variants were isolated
      to possess more antiviral activity in the range of 4-16-fold than parental phage
      IFN after IPTG-induced soluble expression. The results suggest that phage
      displayed phage-IFN alpha1c/86D variants with increased specific activity might
      be obtained after purification procedures.

PMID- 18726474
TI  - Adenovirus-mediated transfer of RA538 gene and its antitumor effect.
AB  - The RA538 cDNA was transferred into human ovarian cancer cell line SK-OV-3 and
      human melanoma cell line WM-983A by its recombinant adenoviral vector constructed
      through homologous recombination. It was demonstrated that the recombinant
      adenovirus could transfer RA538 gene with high efficiency, and could obviously
      inhibit tumor growth, with the inhibiting rates of 85% and 73% respectively, at
      the same time greatly repress the colony forming ability of the cells. The
      therapeutic experiments on transplanted subcutaneous tumor model in nude mice
      demonstrated that RA538 could significantly inhibit tumor growth. Flow cytometry
      and DNA fragmentation analysis indicated that RA538 could induce the cell cycle
      G1 arrest/apoptosis of the tumor cells. The expression of c-myc gene was found
      pronouncedly reduced by Western blot analysis. These results suggest that the
      RA538 recombinant adenovirus could be a promising drug in cancer gene therapy.

PMID- 18726475
TI  - Inhibition of metastasis to lung of a human nasopharyngeal carcinoma cell line
      CNE- 2L2 transfected with pRc/ CMV-antisense 6A8 cDNA in nude mice.
AB  - The growth of CNE-2L2 cell, a cloned line of human nasopharyngeal carcinoma with
      a high potentiality of metastasis to lung was inhibited to a certain extent after
      transfection with a recombinant antisense expression vector of a cDNA encoding a
      human alpha-mannosidase (pRc/CMV-antisense 6A8 cDNA) (the Genbank accession
      number of 6A8 cDNA is U37248) in comparison with that of the cell transfected
      with the Mock and of the wild cell. Two months after a subcutaneous inoculation
      of CNE-2L2 cell into the axilla of nude mice metastatic lesions in the lung were
      observed in 9/10 mice (90%) with grade III in 8 mice and grade II in one mouse in
      the wild cell group, in 6/8 mice (75 %) with grade III in one mouse, grade II in
      2 mice and grade I in 3 mice in the Mock-transfection group, in only 3/10 mice
      (30%) with all grade I in pRc/CMV-antisense 6A8 cDNA-transfection group.

PMID- 18726476
TI  - A novel receptor-targeted gene delivery system for cancer gene therapy.
AB  - Some growth factor receptors, such as insulin like growth factor I and II
      receptor (IGF I R, IGF II R) and epidermal growth factor receptor (EGF R), have
      been proved to be over-expressed in a variety of human cancers derived from
      different tissue origins. Based on this molecular alteration, a polypeptide
      conjugate gene delivery system was designed and synthesized. It contains three
      essential moieties: a ligand oligopeptide (LOP) for receptor recognition, a
      polycationic polypeptide (PCP) such as protamine (PA) or poly-L-lysine (PL) as a
      backbone for DNA binding and an endosome-releasing oligopeptide (EROP) such as
      influenza haemagglutinin oligopeptide (HA20) for endosomolysis. These components
      are covalently conjugated as LOP-PCP-HA20 or in the form of a mixture of LOP-PCP
      and HA20-PCP. A 14 amino acid E5 was designed and synthesized as LOP for IGF I R
      and IGF II R, and a 16 amino acid GE7 as LOP for EGF R. Both E5 and GE7 systems
      could form stable complex with the plasmid DNA as E5-PCP/ DNA/PCP-HA20 and GE7
      PCP/DNA/PCP-HA20. Using bacterial beta-galactosidase gene (pSVbeta-gal) as a
      reporter, the present system is able to efficiently target exogenous gene to
      human cancer cells of different tissue types with high efficiency both in vitro
      and in implanted tumors in nude mice. It was also demonstrated that the
      transduced genes were highly expressed in cancer cells both in vitro and in vivo.
      The present system will provide a novel effective vehicle to target therapeutic
      genes into cancer cells in gene therapy.

PMID- 18726477
TI  - Effect of tracheosyringeal denervation on call in greenfinch (Carduelis sinica).
AB  - After sections of left or right tracheosyringeal nerve (NXIIts), greenfinches may
      repeat everyday calls, with no effect on temporal properties. It is suggested
      that either side of syrinx may produce sound alone and ipsilateral innervation of
      NXIIts for the syringeal muscles. After section of left NXIIts, the bird produces
      the vocal pattern of partial tone increase, and effects on the sound intensity
      and sentence length average 1.4 and 2.8 times those after section of right
      NXIIts, suggesting that the innervation of NXIIts has left side dominance. After
      bilateral section of NXIIts, the call rhythm in company with expiratory motions
      is 98-146 times/min, on an average, and lose all sentence types and syllable
      structure of normal call. But the call spectra produced by tympaniform membrane
      vibrations without innervation still reserve frequency components similar to the
      tonic frequency and harmonics of normal calls.

PMID- 18726478
TI  - A novel gene-samfR involved in early stage of Streptomyces ansochromogenes
      differentiation.
AB  - A 4.6 kb DNA fragment was cloned from the DNA library of Streptomyces
      ansochromogenes using a partial DNA fragment located in the downstream of
      promoter-P(TH4) as probe. The experiments revealed that this DNA fragment
      consists of saw D gene and a 1.4 kb Pvu II fragment which can accelerate mycelium
      formation o fS. ansochromogenes. The nucleotide sequence of 1.4 kb DNA fragment
      was determined and analysed; the result indicated that the fragment contains one
      complete open reading frame (ORF) which encodes a protein with 213 amino acids,
      and this gene was designated as samfR. The deduced protein has 36% amino acid
      identities and 52% amino acid similarities in comparison with that encoded by
      hppR gene, which is involved in the regulation of catabolism for 3-(3
      hydroxyphenyl) propionate (3HPP) in Rhodococcus globerulus. The function of samfR
      gene was studied using strategy of gene disruption, and the resulting samfR
      mutant failed to form aerial hyphae and spores, its development and
      differentiation stopped at the stage of substrate mycelium in contrast with wild
      type strain. The results showed that the samfR gene is closely related to S.
      ansochromogenes differentiation.

PMID- 18726479
TI  - Preparation and epitope characterization of monoclonal antibodies against firefly
      luciferase.
AB  - The 6-His tagged firefly luciferase was highly expressed inE. coli and purified
      to homogeneity by affinity chromatography and gel filtration. After immunizing
      Balb/c mice with the antigen, 6 hybridomas clones were found to secrete
      monoclonal antibodies (mAbs) and the mAbs were also purified separately. The
      competitive binding experiments show that 2 mAbs can bind heat-denatured antigen
      or its proteolytic fragments but not the native luciferase, suggesting that their
      epitopes might be accommodated in the internal segments of the protein. On the
      other hand, the other 4 mAbs are capable of binding both native and denatured
      antigens. It infers that their epitopes locate in the segments on the protein
      surface. The results also suggest that the six mAbs are all sequence-specific.

PMID- 18726480
TI  - Expression of tPA, LH receptor and inhibin alpha, beta(A) subunits during
      follicular atresia in rats.
AB  - By using DNA 3'-end labeling, immunocytochemistry and mRNA in situ hybridization
      detection techniques, the expression of inhibin subunits and LH receptor in the
      granulosa cells and tissue-type plasminogen activator (tPA) in the oocytes has
      been studied in relation to follicular development and atresia. The results
      demonstrated that: (i) tPA activity in the oocytes of normal developing follicles
      is undetectable, and increases significantly in the follicle undergoing atresia;
      (ii) the production of inhibin subunits in granulosa cells is negatively
      correlated with the expression of oocyte tPA activity, indicating that they may
      be an important regulator of oocyte tPA production and follicular development;
      (iii) in atretic follicles, granulosa cells do not express LH receptor and
      inhibin subunits. It is therefore suggested that tPA may play a role in oocyte
      self-destruction and clearance in some of atretic follicles, and inhibin of
      granulosa-origin might be an inhibitory factor for the translation of tPA in the
      oocyte.

PMID- 18726481
TI  - Study of thrombopoietin for gene therapy of thrombocytopenia.
AB  - Thrombopoietin (TPO) is likely to he a potent, specific and reliable medication
      in the treatment of thrombocytopenia. A TPO-highly-expressed plasmid pcDNA3-TPO
      was constructed and a primary study was made on the expression of TPO cDNA in
      vitro and gene transfer study for thrombocytopenia in vivo. rhTPO showed complete
      and stable bioactivity by a series of indicators. High expression of TPO was
      detected in plasma from healthy mice or thrombocytopenia mice model receiving
      direct intramuscular injection of pcDNA3-TPO. And the platelet level of healthy
      mice peaked to 1.9-fold of baseline. Mice with CTX-induced thrombocytopenia
      achieved profound nadirs, acceleration of recovery, even 1.8-2.0-fold supranormal
      levels of peripheral platelet counts. The results offered experimental support
      for clinical application of gene therapy for thrombocytopenia via direct
      intramuscular injection of TPO cDNA.

PMID- 18726482
TI  - Construction and characterization of a bacterial artificial chromosome library of
      thermo-sensitive genic male-sterile rice 5460S.
AB  - In order to develop a detailed physical map of the thermo-sensitive genic male
      sterile (TGMS) gene-encompassing region and finally clone the TGMS gene, a high
      quality rice bacterial artificial chromosome (BAC) library from TGMS rice 5460S
      was constructed. The method of constructing BAC library was examined and
      optimized. The 5460S library consists of 19 584 BAC clones with an average insert
      size of 110 kb, which represents about 5 times rice haploid genome equivalents.
      Rice inserts of up to 140 kb and 250 kb were isolated and appeared stable after
      100 generations of serial growth. Hybridization of BAC clones with mitochondrial
      and chloroplastic genes as probes demonstrated that this library has no
      organellar contamination. The 5460S library was screened with 3 molecular markers
      linked to tms 1 gene as probes and at least 1 BAC clone was identified with each
      probe. The insert ends of positive clones were successfully isolated using
      thermal asymmetric interlaced PCR (TAIL-PCR) technique.

PMID- 18726483
TI  - The complete genomic sequence of egg drop syndrome virus strain AAV-2.
AB  - In the search for the genome of egg drop syndrome virus (EDSV-76) Chinese strain
      AAV-2, part of restriction endonuclease physical map is analyzed, the complete
      genomic library is organized. On basis of this, the complete genome nucleotide
      sequences (32 838 bp in length, including terminal structures) are determined.
      The data analysis shows: compared with the other Adenoviruses, strain AAV-2 has
      more disparity on genomic structure and the distribution of open reading frame
      (ORF). There are no clear E1, E3 and E4 regions in AAV-2 genome. Two segments
      located at both ends of genome (1.1 kb and 8.3 kb in length respectively) have no
      homology with the other adenovirus genomes. In addition, strain AAV-2 genome
      lacks ORFs encoding ElA, pV and pIX, which are common ORFs encoding early, lately
      proteins in Adenovirus. This reveals differences between EDSA-76, the sole
      standard strain of group III Avian Adenoviruses, and the other Avian Adenoviruses
      for the first time. It will help the search for Avian Adenovirus and will also
      help the search of all Adenoviruses.

PMID- 18726484
TI  - The positive and negative control actions of PTPase on IL-2 signaling.
AB  - The tyrosine phosphorylation of intracellular proteins was greatly increased
      after the treatment of cells with sodium n-vanadate, the inhibitor of protein
      tyrosine phosphatase (PTPase). It was found by using EMSA that during this period
      the signal transducer and activator of transcription 5 (STAT5) were tyrosine
      phosphorylated and activated STAT5 may bind to v-interferon activated sequence
      (GAS). Contrast to the activation of STAT5 by interleukin-2 (IL-2), the
      activation for STATS by sodium n-vanadate cannot be completely blocked by the
      inhibitor of protein tyrosine kinase (PTK). In addition, sodium n-vanadate may
      augment the IL-2 up-regulation on the expression of reporter genes containing GAS
      in their promoter regions. All the results here show that PTPase may negatively
      regulate the JAK-STAT signal transduction pathway induced by IL-2. However, the
      inhibition of PTPase activity may block the induction of tnf-beta gene and c-myc
      gene transcription by IL-2 and ultimately results in cell death. Therefore,
      PTPase plays positive or negative control roles on different signaling pathways
      induced by IL-2. Both actions of PTPase are offered through its phosphatase
      activity.

PMID- 18726485
TI  - Fast repair of dAMP hydroxyl radical adduct by verbascoside via electron
      transfer.
AB  - DNA damaged by oxygen radicals has been implicated as a causative event in a
      number of degenerative diseases, including cancer and aging. So it is very
      important to look for ways in which either oxygen radicals are scavenged prior to
      DNA damage or damaged DNA is repaired to supplement the cells' inadequate repair
      capacity. The repair activity and its mechanism of verbascoside, isolated from
      Pedicularis species, towards dAMP-OH . was studied with pulse radiolytic
      technique. On pulse irradiation of nitrous oxide saturated 2 mmol/L dAMP aqueous
      solution containing verbascoside, the transient absorption spectrum of the
      hydroxyl adduct of dAMP decayed with the formation of that of the phenoxyl
      radical of verbascoside well under 100 microseconds after electron pulse
      irradiation. The result indicated that dAMP hydroxyl adducts can be repaired by
      verbascoside. The rate constants of the repair reaction was deduced to be 5.9 x
      10(8) dm(3) * mol(-1) * s(-1). A deeper understanding of this new repair
      mechanism will undoubtedly help researchers explore new prevent and/or
      intervening medicine.

PMID- 18726486
TI  - Skeletal muscle-specific expression of human blood coagulation factor IX rescues
      factor IX deficiency mouse by AAV-mediated gene transfer.
AB  - The efficacy of recombinant adeno-associated virus (AAV) vector to deliver and
      express human blood clotting factor IX (hFIX) gene in skeletal muscle of
      coagulation factor IX deficiency mouse strain (FactorIX-knockout) is evaluated.
      The muscle creatine kinase enhancer (MCK) and beta-actin promoter (betaA) were
      used to drive the hFIX minigene (hFIXml), which was flanked by AAV inverted
      terminal repeats (ITRs). Following intramuscular injection of high titer (2.5 x
      10(11) vector genomes/mL) of rAAV, increased hFIX expression (256 ng/mL of
      plasma) was achieved. The time course of hFIX expression demonstrated that the
      expression level gradually increased over a period of two weeks before anti-hFIX
      antibodies developed in mouse circulating plasma. Those results provided a
      promising evidence that rAAV-mediated gene transfer and skeletal muscle-specific
      expression of hFIX is a feasible strategy for treating patients for hemophilia B.

PMID- 18726487
TI  - Mechanisms of arsenic trioxide induced apoptosis of human cervical cancer HeLa
      cells and protection by Bcl-2.
AB  - It was recently reported that arsenic trioxide (As(2)O(3)) can induce complete
      remission in patients with acute promyelocytic leukemia (APL). In this present
      article, the biological effect of (As(2)O(3)) on human cervical cancer HeLa cells
      and HeLa cells overexpressing Bcl-2 is studied. By MTT and colony forming ability
      assays, morphology alteration, flow cytometric analysis, DNA gel electrophoresis
      and in situ cell death detection (TUNEL), it was found that As(2)O(3) inhibited
      the growth of HeLa cells and induced G2/M arrest and apoptosis of the cells. RT
      PCR, Northern blot, Western blot analysis revealed that As(2)O(3) induced HeLa
      cell apoptosis possibly via decreasing the expression of c-myc and viral genes.
      HeLa cells overexpressing Bcl-2 partly resist As(2)O(3) induced apoptosis, which
      might be relative to preventing the cells from As(2)O(3) caused G2/M block,
      downregulation of c-myc gene expression and inhibition of viral gene expression
      was also noted. However, it was found that As(2)O(3) at a high concentration
      could also induce apoptosis of HeLa cells overexpressing Bcl-2 possibly mainly
      via downregulating Bcl-2 expression and slightly inhibiting viral gene
      expression.

PMID- 18726488
TI  - Tracking bacterial growth in liquid media and a new bacterial life model.
AB  - By increasing viscosity of liquid media above 8.4 centipoise (cp) i.e. 0.084 g *
      cm(-1) * s(-1), individual growth and family formation of Escherichia coli was
      continuously observed in real-time for up to 6 h. The observations showed
      primarily unidirectional growth and reproduction of E. coli and suggested more
      than one reproduction in the observed portion of E. coli life span. A new
      bacterial life model is proposed: each bacterium has a stable cell polarity that
      ultimately transforms into two bacteria of different generations; the life cycle
      of a bacterium can contain more than one reproduction cycle; and the age of a
      bacterium should be defined by its experienced chronological time. This new
      bacterial life model differs from the dominant concepts of bacterial life but
      complies with all basic life principles based on direct observation of
      macroorganisms.

PMID- 18726489
TI  - Expression of recombinant rat Neurotrophin-3 in Chinese hamster ovary cells.
AB  - The CHO cell line stably producing recombinant rat NT-3 was established. The
      insertion of rNT-3 cDNA into transferred cell gonome was analyzed with Southern
      blot. The expressed protein was identified by Dot ELISA (enzyme-linked
      immunosorbent assay) and Western blot. Western blot showed a clear specific band
      of about 14 ku for NT-3. The mean level of rNT-3 in four NT-3cDNA/CHO cell lines
      was about 2 100 ng/10(6) cells/48 h determined by EIA. The conditioned-medium
      (CM) of NT-3cDNA/CHO cells could promote the fiber outgrowth of the dissociated
      dorsal root ganglion of 8-day-old chick embryos, which shows a dose-response
      relationship. A half-maximal concentration of the biological activity (EC50) of
      the recombinant protein was approximately 16.7 ng/mL. The MoAb 3W3 of NT-3 could
      neutralize the biological activity of the rNT-3.

PMID- 18726490
TI  - Mapping of a BYDV resistance gene from Thinopyrum intermedium in wheat background
      by molecular markers.
AB  - The wheat line H960642 is a homozygous wheat-Thinopyrum intermedium translocation
      line with resistance to BYDV by genomic in situ hybridization (GISH) and RFLP
      analysis. The genomic DNA of Th. intermedium was used as a probe, and common
      wheat genomic DNA as a blocking in GISH experiment. The results showed that the
      chromosome segments of Th. intermedium were transferred to the distal end of a
      pair of wheat chromosomes. RFLP analysis indicated that the translocation line
      H960642 is a T7DS-7DL-7XL translocation by using 8 probes mapped on the
      homoeologous group 7 in wheat. The translocation breakpoint is located between
      Xpsr680 and Xpsr965 about 90-99 cM from the centromere. The RFLP markers psr680
      and psr687 were closely linked with the BYDV resistance gene. The gene is located
      on the distal end of 7XL around Xpsr680 and Xpsr687.

PMID- 18726491
TI  - Translocation of chicken heart apocytochrome c and its mutants (C17S, H18D)
      across mitochondrial membrane.
AB  - The dependence of import of chicken heart apocytochrome c on its transformation
      to holoform by heme attachment was studied. Results showed that there was no
      difference in the translocation of apocytochrome c across the mitochondrial
      membrane in the presence or absence of hemin + dithionite. Furthermore, two heme
      unattached mutants (H18D. C17S) were prepared, which could still be accumulated
      in mitochondria, but their import velocity was obviously reduced.

PMID- 18726492
TI  - Murine neurofibroma reversion by antisense RNA for HTLV-I tax.
AB  - Neurofibroma cell lines derived from mice transgenic for HTLV-I LTR tax express
      high levels of HTLV-I tax mRNA and protein and exhibit a transformed phenotype. A
      retrovirus vector carrying HTLV-I tax cDNA in reversed transcriptional
      orientation was stably transfected into the neurofibroma cells. Antisense RNA
      inhibited expression of the tax gene with a decrease of more than 40% in both tax
      mRNA and protein. Tax antisense RNA reversed the transformed phenotype as
      exhibited by dramatic changes in cell morphology and growth characteristics.
      Expression of several cellular genes which are activated by Tax protein including
      GM-CSF, IL-6, LT/TNF, c-myc and LIF was down-regulated, while M-CSF and c-src
      proto-oncogene expressions were up-regulated. Accumulation of beta-actin mRNA was
      not affected. The changes that occurred in the tax antisense expressing
      neurofibroma cells could be the consequence of the decreased concentration of Tax
      protein. These results also indicate that HTLV-I Tax protein is crucial for
      maintaining the transformed cell morphology, growth and proliferation of murine
      neurofibroma cells and suggest that deregulation of endogenous cellular genes by
      Tax protein is the mechanism through which neurofibromas occur in tax mice.

PMID- 18726493
TI  - Direct differentiation of ears and tassels from cultured shoot apices of maize.
AB  - In vitro morphogenesis of inflorescences from the cultured corn seedling shoot
      tips was obtained on modified Murashige and Skoog (MS) medium in complete
      darkness. Some shoot tip meristems excised from seedlings of inbred line 515,
      inbred line 8112 and their filial generations would directly give rise to florets
      on modified MS medium supplemented with 2.0 mg/L N(6) -bezyladenine (6-BA) in
      five or six weeks. On the medium with 1.0 mg/L 6-BA and 0.2 mg/L 2, 4
      dichlorophenoxy acetic acid (2,4-D), the explants swelled first, and produced
      multiple shoot clumps, then the culture of the shoot tips from all of the six
      inbred lines in experiment would ultimately initiate to develop ears and tassels
      accompanied by multiple shoot clumps developing on the medium with 1.0 mg/L 6-BA
      and 0.2 mg/L indole-3-butyric acid (IBA). The developmental patterns of the corn
      inflorescences were similar to the controls of normal plants in the field, but
      the number of the ears was much more than that of the tassels in vitro. It seemed
      that proper kinds and concentrations of exogenous hormones were necessary for the
      initiation and development of the inflorescences. The genotype of explants was
      responsible for the response to culture conditions. It could be inferred that
      there were different control mechanisms existing in the vegetative and
      reproductive developmental processes of maize, because the cultured shoot tips
      could directly produce the reproductive organs.

PMID- 18726494
TI  - Construction of shuttle, expression vector of human tumor necrosis factor alpha
      (hTNF-alpha) gene and its expression in a cyanobacterium, Anabaena sp. PCC 7120.
AB  - The construction of the shuttle, expression vector of human tumor necrosis factor
      alpha (hTNF-alpha) gene and its expression in a cyanobacterium Anabaena sp. PCC
      7120 was reported. The 700-bp hTNF cDNA fragments have been recovered from
      plasmid pRL-rhTNF, then inserted downstream of the promoter PpsbA in the plasmid
      pRL439. The resultant intermediary plasmid pRL-TC has further been combined with
      the shuttle vector pDC-8 to get the shuttle, expression vector pDGTNF. The
      expression of the rhTNF gene in Escherichia coli has been analyzed by SDS-PAGE
      and thin-layer scanning, and the results show that the expressed TNF protein with
      these two vectors is 16.9 percent (pRL-TC) and 15.0 percent (pDC-TNF) of the
      total proteins in the cells, respectively, while the expression level of TNF gene
      in plasmid pRL-rhTNF is only 11.8 percent. Combined with the participation of the
      conjugal and helper plasmids, pDC-TNF has been introduced into Anabaena sp PCC
      7120 by triparental conjugative transfer, and the stable transgenic strains have
      been obtained. The existence of the introduced plasmid pDC-TNF in recombinant
      cyanobacterial cells has been demonstrated by the results of the agarose
      electrophoresis with the extracted plasmid samples and Southern blotting with
      alpha-(32)P labeled hTNF cDNA probes, while the expression of the hTNF gene in
      Anabaena sp. PCC 7120 has been confirmed by the results of Western blotting with
      extracted protein samples and human TNF-alpha monoclonal antibodies. The
      cytotoxicity assays using the mouse cancer cell line L929 proved the cytotoxicity
      of the TNF in the crude extracts from the transgenic cyanobacterium Anabaena sp.
      PCC 7120.

PMID- 18726495
TI  - Composition and structure of nucleolar skeleton (nucleolar matrix) : Actin and
      fibrillarin are two main protein components of nucleolar skeleton.
AB  - Purified nucleoli of HeLa cells were treated sequentially with nonionic
      detergent, nucleic acid enzyme, low salt and high salt. The residual nucleolar
      structure termed nucleolar skeleton (nucleolar matrix) was shown as a fine
      network under electron microscope with DGD embedding-unembedding technique. Such
      structures of BHK-21 cell and mouse liver cell are similar to that of HeLa cell.
      The protein composition of the nucleolar skeleton of HeLa cells was analyzed. The
      protein composition of such nucleolar residual shows obvious difference from the
      compositions of nuclear matrix and chromosome scaffold. The major protein
      composition of the nucleolar skeleton of HeLa cells contains 6-7 polypeptides.
      Their molecular weights are about 48, 43, 36 and 33 ku. Further studies show that
      actin and fibrillarin are two major protein components of nucleolar skeleton of
      HeLa cells.

PMID- 18726496
TI  - Screening and identification of receptor antagonist for shiga toxin from random
      peptides displayed on filamentous bacteriophages.
AB  - The bacteriophage clones which can bind with shiga toxin B subunit (StxB) and
      inhibit cytotoxicity of shiga toxin were obtained by using antibody capturing
      method from a 15-mer random peptide library displayed on the surface of
      bacteriophage fd. Among them, one peptide encoded by the random DNA region of a
      selected bacteriophage (A12) was synthesized and tested in vitro and in vim,
      where the peptide competed with the receptor of shiga toxin to bind StxB, and
      inhibited the cytotoxicity and enterotoxicity of shiga toxin. The peptide can
      also block other apparently unrelated StxB binding bacteriophage (A3), which
      suggests that there are overlapping StxB interaction sites for those ligands with
      different sequences. The results provide a demonstration of bacteriophage display
      to screen peptide ligands for a small and/or unable biotinylated molecule by
      antibodies-capturing strategy, and take the lead for the development of receptor
      antagonists for shiga toxin.

PMID- 18726497
TI  - Sequence analysis of leader and trailer regions of rice yellow stunt rhabdovirus
      and characterization of their in vivo transcripts.
AB  - The 3' leader and the 5' trailer of the rice yellow stunt rhabdovirus (RYSV)
      genomic RNA have been cloned and sequenced. Sequence data indicate that the RYSV
      leader region is composed of 203 nucleotides (nt) and the trailer region 191 nt.
      The terminal 9 nt of the two regions are complementary and capable of forming a
      putative panhandle structure common to rhabdovirus genomes. In comparison with
      the leader or trailer sequences of other rhabdoviruses reported so far, both the
      leader and trailer of RYSV are the longest and there is no obvious sequence
      homology between the counterparts except for a few terminal nt and the UGUU motif
      in the leader sequences. Polyadenylated plus-strand leader RNA has been detected
      in RYSV-infected rice plants by 3' RACE. This is the second example in
      rhabdoviruses following the report for sonchus yellow net virus (SYNV) for
      existence of a polyadenylated leader RNA. No polyadenylated plus-strand
      transcripts of the RYSV trailer have been found using the similar method.

PMID- 18726498
TI  - Studies on kinetics and thermodynamics of biomachining pure copper.
AB  - The kinetics and thermodynamics of biomachining pure copper by Thiobacillus
      ferrooxidans were quantitatively analyzed. The kinetic effect of bacteria on the
      ion-cycle between Fe(2+) and Fe(3+) and the thermodynamic effect of hydrolysis on
      the changes of pH in biomachining processes were expounded through six series of
      experiment. Finally a model of ion-cycle in the biomachining processes was
      proposed, and the measures for maintaining the stable equilibrium of the ion
      cycle were also discussed.

PMID- 18726499
TI  - Insulin and insulin mutants stimulate glucose uptake in rat adipocytes.
AB  - A simple method to determine the in vitro biological activity of insulin by
      measuring glucose uptake in the rat adipocytes is presented here. In the presence
      of insulin, the glucose uptake is 5-6 times more than the basal control. And the
      uptake of D-[3-(3)H]-glucose is linear as the logarithm of insulin concentration
      from 0.2 microg/L to 1.0 microg/L. Glucose and 3-O-methyl-glucose inhibit D-[3
      (3)H]-glucose uptake into adipocytes. By this method, the in vitro biological
      activity of [B(2)-Lys]-insulin and [B(3)-Lys]-insulin was measured to be 61.6%
      and 154% respectively, relative to that of insulin.

PMID- 18726500
TI  - Analysis and location of a rice BAC clone containing telomeric DNA sequences.
AB  - BAC2, a rice BAC clone containing (TTTAGGG)(n) homologous sequences, was analyzed
      by Southern hybridization and DNA sequencing of its subclones. It was disclosed
      that there were many tandem repeated satellite DNA sequences, called TA352, as
      well as simple tandem repeats consisting of TTTAGGG or its variant within the
      BAC2 insert. A 0. 8 kb (TTTAGGG)(n)-containing fragment in BAC2 was mapped in the
      telomere regions of at least 5 pairs of rice chromosomes by using fluorescencein
      situ hybridization (FISH). By RFLP analysis of low copy sequences the BAC2 clone
      was localized in one terminal region of chromosome 6. All the results strongly
      suggest that the telomeric DNA sequences of rice are TTTAGGG or its variant, and
      the linked satellite DNA TA352 sequences belong to telomere-associated sequences.

PMID- 18726501
TI  - A new model of phycobilisome in Spirulina platensis.
AB  - Phycobilisomes (PBS) were isolated from blue-green alga Spirulina platensis.
      Scanning tunneling microscope was used to investigate the three-dimensional
      structure of PBS deposited on freshly cleaved highly oriented pyrolytic graphite
      (HOPG) in ambient condition at room temperature. The results showed that the rods
      of PBS radiated from the core to different directions in the space other than
      arrayed in one plane, which was different from the typical hemi-discoidal model
      structure. The diameter of PBS was up to 70 nm, and the rod was approximately 50
      nm in length. Similar results were observed in Langmuir-Blodgett (LB) film of
      PBS. The dissociated PBS could reaggregate into rod-like structures and easily
      form two-dimensional membrane while being absorbed on HOPG, however, no intact
      PBS was observed. The filling-space model structure of PBS in Spirulina platensis
      with STM from three-dimensional real space at nanometer scale was found, which
      showed that this new structural model of PBS surely exists in blue-green algae
      and red algae. The function of this structural model of PBS was also discussed.

PMID- 18726502
TI  - Refined structure of basic phospholipase A2 from venom of Agkistrodon halys
      Pallas in orthorhombic crystal form I at 0.25 nm resolution.
AB  - The basic phospholipase A2 from the venom of Agkistrodon halys Pallas is a potent
      hemolytic toxin and anticoagulant. The accurate rotation and translation
      parameters of the molecules in orthorhombic crystal form I were successfully
      obtained using the fitting refinement technique. The structure was refined in the
      resolution range of 0.6-0.25 nm using least square refinement with non
      crystallographic two fold symmetry restraint, and resulted in the final R factor
      of 20.1 %, and the rms deviations from ideal stereochemistry were 0.001 3 nm for
      bond lengths and 1.32 degrees for bond angles. The overall architecture of the
      present structure was similar to that of the determined structure of the
      orthorhombic crystal form II, with a few differences in the regions of the beta
      wing and Ca(2+) -binding Imp. The dimers formed by the two molecules in the
      asymmetric unit in both crystal forms were also similar. However, one of the
      monomers showed an orientational difference of 5.5 degrees along the dimer
      interface in the two crystal forms, suggesting the flexibility of the interface
      of the dimer to some degree. The molecular packing of the dimer in crystal form I
      was much more compact than that in crystal form II.

PMID- 18726503
TI  - Transfer of E. coli gutD gene into maize and regeneration of salt-tolerant
      transgenic plants.
AB  - GutD gene, encoding a key enzyme (glucitol-6-phosphate dehydrogenase) of sugar
      alcohol metabolic pathway inE. coli, was transferred into maize. Results of
      Southern and Western blotting analysis certified that this gene had integrated
      and been expressed in transgenic maize plants and their progeny. The synthesis
      and accumulation of sorbitol were detected in transgenic maize plants and a
      preliminary nutrient solution culture experiment showed that gutD transgenic
      maize plants had an increased tolerance to salt stress compared with
      nontransgenic ones.

PMID- 18726504
TI  - Reduction of lesion growth rate of late blight plant disease in transgenic potato
      expressing harpin protein.
AB  - Using harpin protein gene from apple fire blight pathogen Erwinia amylovora and
      potato prp1-1 promoter as main DNA elements, the feasibility of using pathogen
      infection-induced hypersensitive response was explored as a new strategy of
      engineering fungal disease resistance. Three plant transformation vectors were
      constructed and 68 transgenic potato plants were produced through Agrobacterium
      mediated transformation method. Southern, Northern and Western blot analysis
      demonstrated the insertion, transcription and protein expression of harpin
      protein gene in transgenic plants. Disease resistance test using a complex race
      of Phytophthora infestans as challenging pathogen showed that both constitutive
      and pathogen infection-induced expression of harpin protein gene in transgenic
      potato reduced the lesion growth rate of fungus. Among plants where harpin
      protein gene expression was induced only by fungus infection, two plants were
      found to be highly resistant to P.infestans infection. Fungal hyphae were not
      produced on total of 30 inoculated leaves from the two resistant plants and
      necrotic lesion was limited to inoculation area. The results highlighted that
      engineered hypersensitive response in plants was a very promising approach to
      produce fungal disease resistant genotype.

PMID- 18726505
TI  - A study on population genetic structure of Oryzu meyeriana (Zoll. et Mor. ex
      Steud.) Baill. from Yunnan and its in situ conservation significance.
AB  - In order to determine genetic diversity of Oryza meyeriana (Zoll. et Mor. ex
      Steud.) Baill., 12 enzyme systems encoded by 17 loci were electrophoretically
      analyzed in 164 individuals of seven populations from Simao Prefecture, Yunnan
      Province, China. In comparison with those seed plants with the same life history
      and breeding systems, as well as the other species in the genus Oryza, the
      species shows rather low levels of genetic diversity (A = 1.1,P = 8.0 %, Ho =
      0.004 and He = 0.015) within populations and high genetic differentiation among
      populations. F(st) was up to 0. 649, suggesting that 64. 9% of total genetic
      variability exists among populations. Considering high genetic differentiation
      among populations from a limited geographic region, most of the populations of
      the species are worth being protected, and therefore, great natural protection
      regions should theoretically be established in which a great deal of populations
      should be involved for developing in situ conservation management. Meanwhile,
      some priory localities for in situ conservation of O. meyerzana in Yunnan
      Province, were proposed.

PMID- 18726506
TI  - Gene therapy for rat renal anemia with implantation of erythropoietin-transgenic
      myoblasts.
AB  - To investigate whether an erythropoietin (EPO) gene-based therapy could serve as
      an alternative to the repeated injection of rhEPO in treatment to renal anemia,
      the genetically modified myoblasts of rats, named Myo/ EPO, were implanted
      through intramuscular injection to model rats with renal anemia. The hemoglobin
      (Hb) and hematocrit (HCT) of the rats increased from (92.5 +/-3.0) g/L and 0.29+/
      0.04 to the peak values of (103.8 +/-5.0) g/L and 0. 32 +/-0. 04 respectively 14
      d after implantation, and sustained the pre-implantation level for 90 d.
      Otherwise, the control rats implanted with Myo/X, which carried the parent
      retroviral vector, gradually became severe in anemia. The PCR detection for hEPO
      cDNA in the rat muscle adjacent to injection sites indicated that the Myo/EPO
      cells survived for a long period in the muscle of rats. The results primarily
      demonstrate that myoblast gene transfer of EPO is effective for the treatment of
      rat renal anemia.

PMID- 18726507
TI  - Coil-1 of rod domain of NF-L is essential for its assemblyin vivo.
AB  - Neurofilaments take highly ordered structures composed of parallel mays of 10 nm
      filaments linked to each other with frequent cross-bridge. It is composed of
      three components named NF-L, NF-M and NF-H. NF-L is able to form filamentous
      network alone in Sf9 cells, while M could not. To identify which domain is
      essential for the assembly of NF-L, two chimera proteins named ML and MML were
      constructed: ML was composed of the head domain of NF-M and other domains of NF
      L; MML was composed of the head and Coil-1 domains of NF-M and Coil-2 and tail
      domains of NF-L. ML was not only able to form filaments in Sf9 cells, but also co
      assemble with NF-M into parallel filamentous bundles. MML could not assemble into
      filaments. Thus the Coil-1 domain of NF-L was essential for its assembly.

PMID- 18726508
TI  - An inhibitor selective for collagen-stimulated platelet aggregation from the
      salivary glands of hard tickHaemaphysalis longicornis and its mechanism of
      action.
AB  - Soluble materials of salivary glands fromHaemaphysalis longicornis were found to
      inhibit collagen, ADP, and thrombin-stimulated platelet aggregation. One
      inhibitory component was purified to salivary gland homogeneity by a combination
      of gel filtration, ion-exchange, and C(8) reverse phase HPLC. The purified
      activity, named longicomin, is a protein of molecular weight 16 000 on SDS-PAGE
      under both reduced and nonreduced conditions. Collagen-mediated aggegation of
      platelets in plasma and of washed platelets (IC(50) was approximately 60 nmol/L)
      was inhibited with the same efficacy. No inhibition of aggregation stimulated by
      other effectors, including ADP, arachidonic acid, thrombin, ristocetin, calcium
      ionophore A23187, thromboxane A2 mimetic U46619 and 12-O-phorbol-13-myristate
      acetate, was observed. Longiconin had no effect on platelet adhension to
      collagen. Not only platelet aggregation but also release reaction, and increase
      of intracellar ca(2+) level of platelets in response to collagen were completely
      eliminated by longicomin. Increasing amounts of collagen are able to overcome the
      inhibition of aggregation by longicomin, indicating that longicomin probably
      shares with collagen a common receptor. In addition, collagen fibers did not emit
      fluorescence after incubation with isothocyanate-conjugated longicornin,
      indicating that longicomin did not bind directly to collagen fibers. The
      identification and isolation of longicomin demonstrates the existence of a new
      type of platelet inhibitor that should be useful to better undentand the
      mechanism of collagen stimulation of platelets.

PMID- 18726509
TI  - A novel recombinant adeno-associated virus vector packaging system with HSV-1
      amplicon providing helper functions.
AB  - A novel packaging system for producing recombinant adeno-associated virus (rAAV)
      vector was described. Instead of the conventional method for rAAV production by
      two-plasmid co-transfection followed by superinfection with adenovirus 5, an HSV
      1 amplicon system expressing AAV-2 rep and cap genes from their native promoters
      was used to provide complete helper functions for rAAV replicating and packaging.
      This HSV-1 amplicon stock consisted of two kinds of infectious HSV-1 virions, a
      replicating-defective HSV-I amplicon pseudovirus harboring multi-copies of AAV-2
      rep and cap gene and a temperature-sensitive HSV-1 mutant strain ts-KOS. High
      titer rAAV was generated with this new packaging system. This packaging system
      gives a simple and scaleable process for rAAV production.

PMID- 18726510
TI  - Characteristics of photosensitization of Pheophorbide a in liposomal media.
AB  - Pheophorbide a (PPa), a decomposition product of chlorophyll a, is a
      photosensitizer. The photosensitization mechanisms (Type I and Type 11) of PPa in
      simple buffer solutions and in buffer solutions containing double-layered DPPC
      liposomes have been studied using techniques of ESR, spin-trapping, spin
      counteraction and laser flash photolysis. The results showed that adding DPPC
      liposomes to the buffer solution caused an increase of efficiency of
      generating(1)O(2) and PPa-by photoactivating PPa. The increase could be ascribed
      to the disaggregation of hydrophobic PPa caused by the addition of liposomes and
      the protective effect of liposomal media on the triplet state of PPa. It is
      concluded that the photosensitization of PPa in liposomal systems is different
      from that in simple aqueous solutions, and shows higher efficacy. The results
      will be useful to elucidating the mechanisms of photodynamic therapy of cancer.

PMID- 18726511
TI  - Tobacco floral homeotic geneNfbp6 is specifically expressed during pollen and
      ovule development.
AB  - Nfbp6 was a floral homeotic gene isolated from tobacco. It showed high homology
      with other class C genes. Usingin situ hybridization technique, the expression
      ofNfbp6 was investigated in various stages of flower development. The results
      showed thatNfbp6 was expressed at low level during the initiation period of
      stamen and carpel primordia. In the later stage of flower bud development, the
      transcription level ofNfbp6 gene increased especially during the formation of
      pollen and ovule. TheNfbp6 gene expression was also observed in the transmitting
      tissue of style, stomium and circular cell clusters of the anther.

PMID- 18726512
TI  - Assembly characteristics of plant keratin intermediate filamentsin vitro.
AB  - After selective extraction and purification, plant keratin intermediate filaments
      were reassembledin vitro. Scanning tunneling microscope (STM) and transmission
      electron microscope (TEM) micrographs showed that acidic keratins and basic
      keratins can assemble into dimers and further into 10 nm filamentsin vitro. In
      higher mcation images, it can be seen that fully assembled plant keratin
      intermediate filaments consist of several thinner filaments of 3 nm in diameter,
      which indicates the formation of protofilaments in the assembly processes. One of
      the explicit features of plant keratin intermediate filaments is a 24-25 nm
      periodic structural repeat alone the axis of both the 10 nm filaments and
      protofilarnents. The periodic repeat is one of the fundamental characteristic of
      all intermediate filaments, and demonstrates the half staggered arrangement of
      keratin molecules within the filaments.

PMID- 18726513
TI  - The terminal structure plays an important role in the biological activity of
      cecropin CMIV.
AB  - Antibacterial peptides have received increasing attention as a new pharmaceutical
      substance. But the molecular mechanism of lysis is still poorly understood. CMIV
      gene and mutant CMIV gene in GST fusion system were expressed. After cleaving
      with different cleavage reagents, the peptide with an excess of N-terminus and
      with an un-amidated C-terminus stopped the activity while the peptide with an
      excess Asn at the C-terminus had the activity level the same as natural CMIV. The
      results showed that the terminal structure of cecropin CMIV played an important
      role in its biological activity.

PMID- 18726514
TI  - Effect of DNA methylation on protein-DNA interaction of HL-60 cells.
AB  - HL-60 cells have been induced with differentiation index 16% by S-adenosyl-L
      methionine (SAM) as inducer in the presence of optimum concentration of 10
      pmol/L. The methylation level of genome DNA determined by HPLC is increased
      during cell differentiation. When restriction endonucleaseHae III,Sma I,Sal
      I,XhoI andHind III which are sensitive to 5-methyicytoside were used to cleave
      the genome DNA, a resistance effect was found. The interaction between DNA and
      DNA binding proteins is changed by using gel retarding test.

PMID- 18726515
TI  - Molecular cloning, expression analysis and chromosomal mapping of salt-responsive
      cDNAs in rice (Orym sativa L.).
AB  - By using differential display PCR (DD-PCR) technique, two salt-inducible and one
      salt-repressed cDNA fragments were isolated from rice. The three cDNA fragments
      were characterized respectively as partial sequence of rice S-adenosylmethionine
      decarboxylase (SAMDC) gene, a new member of translation elongation factor 1A gene
      (namedREF1 A), and a novel gene whose function is unknown (namedSRG1). The full
      length cDNA of SAMDC gene (namedSAMDC1) was further isolated by RT-PCR approach
      and the deduced polypeptide was found to be homologous to SAMDC proteins of other
      plants, yeast and buman. Northern hybridization revealed that expression of
      SAMDCl and REFlA was induced, while SRGl was dramatically repressed, by salinity
      stress. Southern blot analysis demonstrated that SAMDCl and SRGl were present as
      a single copy gene in rice genome, whereas riceREF1 A gene was organized as a
      gene family. TheREF1 A,SAMDC1, andSRG1 genes were located on chromosome 3,4, and
      6 respectively by RFLP mapping approach using ZYQ8/JX17 DH population and RFLP
      linkage maps.

PMID- 18726516
TI  - Using a GFP-gene fusion technique to study the cell cycle-dependent distribution
      of calmodulin in living cells.
AB  - In this study, a green fluorescent protein (GFP)-calmodulin (CaM) fusion gene
      method was used to examine the distribution of calmodulin during various stages
      of cell cycle. First, it was found that the distribution of CaM in living cells
      changes with the cell cycle. CaM was found mainly in the cytoplasm during G1
      phase. It began to move into the nucleus when the cell entered S phase. At G2
      phase, CaM became more concentrated in the nucleus than in cytoplasm. Second, the
      accumulation of CaM in the nucleus during G2 phase appeared to be related to the
      onset of mitosis, since inhibiting the activation of CaM at this stage resulted
      in blocking the nuclear membrane breakdown and chromatin condensation. Finally,
      after the cell entered mitosis, a high concentration of CaM was found at the
      polar regions of the mitotic spindle. At this time, inhibiting the activity of
      CaM would cause a dismption of the spindle structure. The relationship between
      the stage-specific distribution of CaM and its function in regulating the
      progression of cell cycle was discussed.

PMID- 18726517
TI  - A novel snoRNA gene cluster in yeast is transcribed as polycistronic pre-snoRNAs.
AB  - Small nucleolar RNAs (snoRNAs) play an important role in eukaryotic rRNA
      biogenesis. By combination of a computer search of EMBL database and experimental
      procedure, a novel snoRNA coding sequence (Z8) was screened out and characterized
      from yeastSaccharomyces cerevisiue genome. Z8 snoRNA gene codes a boxC/D
      antisense snoRNA which guides, deduced from structure analysis, the 2'-O-ribose
      methylation at U(2421) of 25S rRNA. After disruption of Z8 snoRNA gene, the
      methylation at corresponding site was abolished, but no gmwth delay was observed
      in various cultural temperatures. Z8 DNA is the first gene of a gene cluster
      consisting of three cognate snoRNA genes which are located on an intergenic
      region of chromosome XIII. This gene cluster is co-transcribed as a polycistronic
      precursor from a + 247 bp U snoRNA gene promoter, followed by processing to
      release individual snoRNAs, representing a new expression pattern of snoRNA
      genes.

PMID- 18726518
TI  - A method of active conformation search based on active and inactive analogues and
      its application to allylamine antimycotics.
AB  - A new program ACSBAIA (Active Conformation Search Based on Active and Inactive
      Analogues) for determination of the active conformations was developed based on
      the rationales that specific functional groups of active analogues could reach
      and interact with the active site of target receptor by means of the change of
      conformations, but that of inactive analogues could not interact with the active
      site owing to conformational restriction. The program consisted of 4 sub
      programs: conformation sampling system, active conformation constraint system,
      inactive conformation exclusion system, and activity prediction system.
      Pharmacophoric conformation of allylamine antimycotics was studied by this
      method. Activities of 2 analogues were predicted and tested. The results
      suggested that the method was scientific and practical. The application of this
      method was not restricted by the three-dimensional structural knowledge of target
      receptor. In the absence of structural information about the receptor, the method
      was particularly applicable.

PMID- 18726519
TI  - Construction of serial deletants and chimeras of multi-kringle containing
      molecules and primary analysis of their functions.
AB  - In comparison of amino acid sequences of 4 kringles of both macrophage
      stimulating protein (MSP) and hepatocyte growth factor (HGF), consensus motif
      sequence was determined. According to this consensus sequence, a pair of
      universal primen were designed. In combination with specific upstream or
      downstream primer of MSP or HGF respectively, serial fragments containing variant
      number of kringle (from 1 to 4) can be obtained by once PCR. By ligating the C
      terminal and N terminal fragments with different combination, serial deletants
      and chimeras of MSP and HGF were constructed. Sequence analysis showed that the
      degeneracy for universal primers and the sequences of those constructed deletants
      and chimeras are desired. Biological assay of these deletants revealed that wild
      type MSP can inhibit the growth of some tumor cell lines and that kringle 1 of
      MSP is essential for function as that of HGF.

PMID- 18726520
TI  - Analysis of nucleotide sequence of wheat yellow mosaic virus genomic RNAs.
AB  - Wheat yellow mosaic virus (WYMV) isolate HC was used for viral cDNA synthesis and
      sequencing. The results show that the viral RNAl is 7 629 nucleotides encoding a
      polyprotein with 2 407 amino acids, from which seven putative proteins may be
      produced by an autolytic cleavage processing besides the viral coat protein. The
      RNA2 is 3 639 nucleotides and codes for a polyprotein of 903 amino acids, which
      may contain two putative non-structural proteins. Although WYMV shares a
      similarity in genetic organization to wheat spindle streak mosaic virus (WSSMV),
      the identities in their nucleotide sequences or deduced amino acid sequences are
      as low as 70 % and 75 % respectively. Based on this result, it is confirmed that
      WYMV and WSSMV are different species withinBymmirus.

PMID- 18726522
TI  - Chondrogenic differentiation of mouse embryonic stem cells promoted by mature
      chondrocytes.
AB  - In order to direct embryonic stem (ES) cells to differentiate into chondrocytes,
      a chondrogenic environment provided by mature chondrocytes was investigated. Flk
      1 positive cells sorted from pre-differentiated mouse ES cells were mixed with
      adult porcine articular chondrocytes, seeded on biodegradable scaffolds, and then
      implanted subcutaneously into nude mice. The cell-scaffold complexes formed
      cartilage tissues after 4 weeks, which was demonstrated by histology and anti
      type II collagen antibody staining. Positive staining of mouse Major
      Histocompatibility Complex class I molecules confirmed that part of the
      chondrocytes were derived from mouse ES cells. The current study established a
      new approach for directing ES cell differentiation.

PMID- 18726521
TI  - Involvement of insulin in early development of mouse one-cell stage embryos.
AB  - Recent studies have suggested that growth factors and hormones play important
      roles in cell proliferation and differentiation during early embryonic
      development. In the present study, we examined the expression and localization of
      insulin in the mouse oocytes and one-cell stage embryos by quantitative ELISA, RT
      PCR, Western blot and immunofluorescence. In the mouse oocytes and one-cell stage
      embryos, expression of insulin was uniformly distributed in the cytoplasm. We
      also examined the expression, activity and localization of mTOR (mammalian target
      of rapamycin) and p70S6K. The expression of mTOR and p70S6K was not significantly
      different at the cell cycle of mouse one-cell stage embryos. mTOR and S6K were
      distributed evenly in the cytoplasm at G1, G2 and M phase phase, but at S phase,
      the distribution of mTOR and S6K was around the pronucleus. At different phases,
      the activity of mTOR fluctuated. We also used the PI3K specific inhibitor
      Wortmannin to investigate the cleavage rate of eggs. The result showed that the
      rate obviously decreased. When the mTOR specific inhibitor Rapamycin was used,
      the first mitotic division of the mouse one-cell stage embryo was delayed. These
      results suggested that insulin was expressed both in mouse oocytes and one-cell
      stage embryos, and may play functional roles in regulation of mouse early
      embryogenesis by activating the signal pathway of PI3K/PKB/mTOR/S6K.

PMID- 18726523
TI  - Establishing a human pancreatic stem cell line and transplanting induced
      pancreatic islets to reverse experimental diabetes in rats.
AB  - The major obstacle in using pancreatic islet transplantation to cure type I and
      some type II diabetes is the shortage of the donors. One of ways to overcome such
      obstacle is to isolate and clone pancreatic stem cells as "seed cells" and induce
      their differentiation into functional islets as an abundant transplantation
      source. In this study, a monoclonal human pancreatic stem cell (mhPSC) line was
      obtained from abortive fetal pancreatic tissues. Pancreatic tissues were taken
      from abortive fetus by sterile procedures, and digested into single cells and
      cell clusters with 0.1% type IV collagenase. Cultured in modified glucose-low
      DMEM with 10% fetal bovine serum (FBS), these single cells and cell clusters
      adhered to culture dishes, and then primary epidermal-like pancreatic stem cells
      started to clone. After digesting with 0.25% trypsin and 0.04% EDTA, fibroblasts
      and other cells were gradually eliminated and epithelioid pancreatic stem cells
      were gradually purified during generations. Using clone-ring selection, the
      mhPSCs were obtained. After addition of 10 ng/mL epidermal growth factor (EGF) in
      cell culture medium, the mhPSCs quickly grew and formed a gravelstone-like
      monolayer. Continuously proliferated, a mhPSC line, which was derived from a male
      abortive fetus of 4 months old, has been passed through 50 generations. More than
      1 x 10(9) mhPSCs were cryo-preserved in liquid nitrogen. Karyotype analysis
      showed that the chromosome set of the mhPSC line was normal diploid.
      Immunocytochemistry results demonstrated that the mhPSC line was positive for the
      pdx1, glucagon, nestin and CK19, and negative for the insulin, CD34, CD44 and
      CD45 protein expression. RT-PCR revealed further that the mhPSCs expressed
      transcription factors of the pdx1, glucagon, nestin and CK19. Also, in vitro
      induced with beta-mercaptoethanol, the mhPSCs differentiated into nerve cells
      that expressed the NF protein. Induced with nicotinamide, the mhPSCs
      differentiated into functional islet-like clusters, as identified by dithizone
      staining, which expressed the transcription factor of the insulin and secreted
      the insulin and C-peptide. Furthermore, the transplantation of mhPSCs-induced
      pancreatic islets into the subcapsular region of the kidney in streptozotocin
      induced diabetic rats could reduce blood glucose levels and prolong the life
      time.

PMID- 18726524
TI  - Microscopic hyperspectral imaging studies of normal and diabetic retina of rats.
AB  - A microscopic hyperspectral imager was developed based on the microscopic
      technology and the spectral imaging technology. Some microscopic hyperspectral
      images of retina sections of the normal, the diabetic, and the treated rats were
      collected by the new imager. Single-band images and pseudo-color images of each
      group were obtained and the typical transmittance spectrums were extracted. The
      results showed that the transmittance of outer nuclear layer cells of the
      diabetic group was generally higher than that of the normal. A small absorption
      peak appeared near the 180th band in the spectrum of the diabetic group and this
      peak weakened or disappeared in the spectrum of the treated group. Our findings
      indicate that the microscopic hyperspectral images include wealthy information of
      retina sections which is helpful for the ophthalmologist to reveal the
      pathogenesis of diabetic retinopathy and explore the therapeutic effect of drugs.

PMID- 18726525
TI  - Immunomodulatory effects of Caulerpa racemosa var peltata polysaccharide and its
      selenizing product on T lymphocytes and NK cells in mice.
AB  - A polysaccharide, CrvpPS, was isolated from Caulerpa racemosa var peltata. It was
      reacted with nano-selenium in distilled water containing ascorbic acid (Vit C) to
      form a stable CrvpPS-nano-Se complex. The immunomodulatory effects of CrvpPS and
      CrvpPS-nano-Se on T lymphocytes subgroups and NK cells in mice were investigated.
      After intragastric administration for 10 days separately, both CrvpPS and CrvpPS
      nano-Se showed significant stimulatory functions to thymus gland of mice.
      Moreover, the CrvpPS-nano-Se induced the percentage of CD3+, CD3+CD4+, NK cells
      and the CD4+/CD8+ value to increase significantly (P < 0.05) when analyzed by
      flow cytometry, which is better than the CrvpPS, sucrose-nano-Se, and even the
      positive drug levamisole.

PMID- 18726526
TI  - Effects of SO2 derivatives on sodium currents in acutely isolated rat hippocampal
      lead-exposed neurons.
AB  - In this study, the effects of acute SO2 derivatives and chronic lead exposure
      together on sodium currents (I(Na)) were investigated in acutely isolated rat
      hippocampal neurons by using the whole-cell patch clamp techniques. We found that
      chronic lead exposure hardly reduced the amplitudes of I(Na). In the normal
      condition, sodium current started to appear at around -70 mV, and reached the
      peak current at around -40 mV. After chronic lead exposure, the data changed to 
      70 and -30 mV. After adding SO2 derivatives, the data changed to -80 and -40 mV,
      respectively. SO2 derivatives caused a significant increase of I(Na) in
      hippocampal chronic-lead exposed neurons. Chronic lead exposure induced a right
      shift of the activation curve and a left shift of the inactivation curve of
      sodium channels. SO2 derivatives caused negative shifts of the activation and
      inactivation curves of I(Na) in hippocampal chronic-lead exposed neurons. Lead
      exposure put off the time reaching the peak of I(Na) activation. SO2 derivatives
      increased the time constants of inactivation after lead exposure. The interaction
      of lead and SO2 derivatives with voltage-dependent sodium channels may lead to
      changes in electrical activity and contribute to worsening the neurotoxicological
      damage.

PMID- 18726527
TI  - Infusion of methylphenidate into the basolateral nucleus of amygdala or anterior
      cingulate cortex enhances fear memory consolidation in rats.
AB  - The psychostimulant methylphenidate (MPD; also called Ritalin) is a blocker of
      dopamine and norepinephrine transporter. It has been clinically used for
      treatment of Attention Deficit and Hyperactivity Disorder (ADHD). There have been
      inconsistent reports regarding the effects of systemically administered MPD on
      learning and memory, either in animals or humans. In the present study, we
      investigated the effect of direct infusion of MPD into the basolateral nucleus of
      amygdala (BLA) or the anterior cingulate cortex (ACC) on conditioned fear memory.
      Rats were trained on a one-trial step-through inhibitory avoidance task. MPD was
      infused bilaterally into the BLA or the ACC, either at '0' or 6 h post-training.
      Saline was administered as control. Memory retention was tested 48 h post
      training. Intra-BLA or intra-ACC infusion of MPD '0' h but not 6 h post-training
      significantly improved 48-h memory retention: the MPD-treated rats had
      significant longer step-through latency than controls. The present results
      indicate that action of MPD in the BLA or the ACC produces a beneficial effect on
      the consolidation of inhibitory avoidance memory.

PMID- 18726528
TI  - Association of beta-fibrinogen gene -148C/T and -455G/A polymorphisms and
      coronary artery disease in Chinese population: a meta analysis.
AB  - The purpose of our study was to evaluate the correlation between the beta
      fibrinogen gene -148C/T and -455G/A polymorphisms and susceptibility to coronary
      artery disease in the Chinese population using a meta-analytic approach. Eligible
      studies about this correlation were identified by searching the PubMed, EMBASE,
      and CNKI databases. Of the 13 identified, 7 (with 1488 cases and 1234 controls)
      involved the -148C/T polymorphism and 9 (with 1023 cases and 1081 controls)
      involved the -455G/A polymorphism. No publication bias was detectable and
      heterogeneity testing found significant differences between the ORs for both
      groups of studies. The combined OR for the 7 studies on susceptibility to
      coronary artery disease in -148T allele carriers compared to the -148C/C wild
      type homozygotes was 1.31 (95%CI: 0.94-1.84, P = 0.11). The combined OR for the 9
      studies on susceptibility to coronary artery disease in -455A allele carriers
      compared to the -455G/G wild-type homozygotes was 1.75 (95%CI: 1.24-2.46, P =
      0.001). Our results suggest the absence of an association between the beta
      fibrinogen gene -148C/T polymorphism and susceptibility to coronary artery
      disease and the possibility that -455G/A polymorphism (in particular, allele A)
      increases susceptibility to this disease in the Chinese population.

PMID- 18726529
TI  - Study on the structure of heteropolymer pp38/pp24 and its enhancement on the bi
      directional promoter upstream of pp38 gene in Marek's disease virus.
AB  - In the latest report, Chloramphenicol acetyltransferase (CAT) gene was used as a
      reporter to investigate the influence of pp38 on its upstream bi-directional
      promoter, and it was found that the co-expression of pp38 and pp24 can
      significantly enhance the transactivity of the bi-directional promoter between
      pp38 gene and 1.8-kb mRNA transcript in genome of Marek's disease virus (MDV). In
      this study, enhanced green fluorescence protein (EGFP) gene was used as another
      reporter to further investigate the promoter activity. The transfection shows the
      promoter has the complete activity under the condition of co-expression of pp38
      and pp24 in the same cells. Immunoprecipitation test was used to verify the
      structure of pp38/pp24 heteropolymer. The pp38-specific monoclonal antibody H19
      was used in this test, and pp38, pp24 or both were prepared from the pcDNA-pp38,
      pcDNA-pp24 or pBud-pp38-pp24 transfected chicken embryonic fibroblast (CEF),
      respectively. Immunoprecipitation indicates that pp24 could be co-precipitated
      with pp38 by MabH19, implying that pp24 and pp38 were able to form a
      heteropolymer in the natural condition. The two separated tests clarify that pp38
      and pp24 form a heteropolymer, which enhances the activity of the promoter.

PMID- 18726530
TI  - Localization and secretory pathways of a 58K-like protein in multi-vesicular
      bodies in callus of Arabidopsis thaliana.
AB  - Multi-vesicular bodies in endocytosis and protoplasts are special cellular
      structures that are considered to be originated from invagination of plasma
      membranes. However, the genesis and function of multi-vesicular bodies, the
      relationship with Golgi bodies and cell walls, and their secretory pathways
      remain controversial and ambiguous. Using a monoclonal antibody against an animal
      58K protein, we have detected, by Western blotting and confocal microscopy, that
      a 58K-like protein is present in the calli of Arabidopsis thaliana and Hypericum
      perforatum. The results of immuno-electron microscopy showed that the 58K-like
      protein was located in the cisternae of Golgi bodies, secretory vesicles, multi
      vesicular bodies, cell walls and vacuoles in callus of Arabidopsis thaliana,
      suggesting that the multi-vesicular bodies may be originated from Golgi bodies
      and function as a transporter carrying substances synthesized in Golgi bodies to
      cell walls and vacuoles. It seems that multi-vesicular bodies have a close
      relationship with the development of the cell wall and vacuole. The possible
      secretory pathways of multi-vesicular bodies might be in exocytosis, in which
      multi-vesicular bodies carry substances to the cell wall for its construction,
      and in endocytosis, in which multi-vesicular bodies carry substances to the
      vacuole for its development, depending on what they carry and where the materials
      are transported. We hence propose that there is more than one pathway for the
      secretion of multi-vesicular bodies. In addition, our results provided a paradigm
      that a plant molecule, such as the 58k-like protein in callus of Arabidopsis
      thaliana, can be detected using a cross-reactive monoclonal antibody induced by
      an animal protein, and illustrate the existence of analog molecules in both
      animal and plant kingdoms.

PMID- 18726531
TI  - Quantitative trait locus analysis of lateral branch-related traits in cucumber
      (Cucumis sativus L.) using recombinant inbred lines.
AB  - A group of 224 recombinant inbred lines (RILs) was derived from a narrow cross
      between 2 cucumber (Cucumis sativus L.) lines, namely, S94 (Northern China type
      with weak lateral branch growth potential and early lateral branch sprouting
      time) and S06 (Northern European type with strong lateral branch growth potential
      and late lateral branch sprouting time). These lines were then used for
      investigating lateral branch-related traits. A total of 36 quantitative trait
      loci (QTLs) were detected for the following 4 lateral branch-related traits:
      lateral branch average length (LBAL), lateral branch total length (LBTL), lateral
      branch number (LBN), and first lateral branch node (FLBN). Further, each QTL
      explained 3.1% (lbtl2.1, spring) to 32.3% (lbn2.3, spring) of the observed
      phenotypic variance. Eleven QTLs (lbal1.1, lbtl1.1, lbn1.2, flbn1.2, etc.) for
      different traits were found to be clustered on the e23m18d-ME23EM6c section (7.4
      cM) of linkage group (LG) 1; further, 15 QTLs (lbal2.1, lbtl2.1, lbn2.1, flbn2.1,
      etc.) were found to be clustered on the S94A1-ME4SA4a section (13.9 cM) of LG2.
      Twenty-one QTLs explained more than 10% of the phenotypic variance. Moreover,
      lbtl1.3 (autumn, 26.2%, logarithm of odds (LOD) = 17.4; spring, 26.9%, LOD =
      17.9) had stable position and contribution in both seasons. Several sequence
      anchor markers (CMBR40, F, CS30, S94A1, CSWTA11B, etc.) were closely linked with
      some QTLs for LBAL, LBTL, LBN, and FLBN, which can be used for the marker
      assisted selection to improve the plant architecture in cucumber breeding.

PMID- 18726532
TI  - Changes in extreme high-temperature tolerance and activities of antioxidant
      enzymes of sacred lotus seeds.
AB  - Sacred lotus (Nelumbo nucifera Gaertn. 'Tielian') seed is long-lived and
      extremely tolerant of high temperature. Water content of lotus and maize seeds
      was 0.103 and 0.129 g H2O [g DW](-1), respectively. Water content, germination
      percentage and fresh weight of seedlings produced by surviving seeds gradually
      decreased with increasing treatment time at 100 degrees C. Germination percentage
      of maize (Zea mays L. 'Huangbaogu') seeds was zero after they were treated at 100
      degrees C for 15 min and that of lotus seeds was 13.5% following the treatment at
      100 degrees C for 24 h. The time in which 50% of lotus and maize seeds were
      killed by 100 degrees C was about 14.5 h and 6 min, respectively. With increasing
      treatment time at 100 degrees C, relative electrolyte leakage of lotus axes
      increased significantly, and total chlorophyll content of lotus axes markedly
      decreased. When treatment time at 100 degrees C was less than 12 h, subcellular
      structure of lotus hypocotyls remained fully intact. When treatment time at 100
      degrees C was more than 12 h, plasmolysis gradually occurred, endoplasmic
      reticulum became unclear, nuclei and nucleoli broke down, most of mitochondria
      swelled, lipid granules accumulated at the cell periphery, and organelles and
      plasmolemma collapsed. Malondialdehyde (MDA) content of lotus axes and cotyledons
      decreased during 0 -12 h of the treatment at 100 degrees C and then increased. By
      contrast, the MDA content of maize embryos and endosperms increased during 5-10
      min of the treatment at 100 degrees C and then decreased slightly. For lotus
      seeds: (1) activities of superoxide dismutase (SOD) and glutathione reductase
      (GR) of axes and cotyledons and of catalase (CAT) of axes increased during the
      early phase of treatment at 100 degrees C and then decreased; and (2) activities
      of ascorbate peroxidase (APX) and dehydroascorbate reductase (DHAR) of axes and
      cotyledons and of CAT of cotyledons gradually decreased with increasing treatment
      time at 100 degrees C. For maize seeds: (1) activities of SOD and DHAR of embryos
      and endosperms and of GR of embryos increased during the early phase of the
      treatment at 100 degrees C and then decreased; and (2) activities of APX and CAT
      of embryos and endosperms and of GR of endosperms rapidly decreased with
      increasing treatment time at 100 degrees C. With decrease in seed germination,
      activities of SOD, APX, CAT, GR and DHAR of axes and cotyledons of lotus seeds
      decreased slowly, and those of embryos and endosperms of maize seeds decreased
      rapidly.

PMID- 18726533
TI  - Genetic diversity of root-nodulating bacteria isolated from pea (Pisum sativum)
      in subtropical regions of China.
AB  - Diversity of 42 isolates from effective nodules of Pisum sativum in different
      geographical regions of China were studied using 16S rRNA gene RFLP patterns, 16S
      rRNA sequencing, 16S-23S rRNA intergenic spacer (IGS) region RFLP patterns and G
      C rich random amplified polymorphic DNA (RAPD). The isolates were distributed in
      two groups on the basis of their 16S rRNA gene RFLP patterns. The 16S rRNA gene
      sequences of strains from 16S rRNA gene RFLP patterns group I were very closely
      related (identities higher than 99.5%) to Rhizobium leguminosarum USDA 2370.
      Group II consisting of WzP3 and WzP15 was closely related to Rhizobium etli
      CFN42. The analysis of the 16S-23S IGS RFLP patterns divided the isolates into 18
      genotypes and four groups. Group I was clustered with R. leguminosarum USDA2370.
      Group II consisted of YcP2, YcP3 and CqP7. The strains of group III were
      distributed abroad. Group IV consisted of WzP3, WzP15 and R. etli CFN42. RAPD
      divided the isolates into nine clusters in which group IV only consisted of YcP2
      and the strains of group V and IX were from Wenzhou and Xiantao, respectively.
      This assay demonstrated the geographical effect on genetic diversity of pea
      rhizobia.

PMID- 18726535
TI  - Labour market conditions, labour force activity and prevalence of psychiatric
      disorders.
AB  - BACKGROUND: At a population level, the extent that labour market conditions
      influence labour force activity among people with psychiatric disorders, remains
      equivocal. Similarly equivocal is the hypothesised relationship between economic
      conditions and the reported prevalence of specific psychiatric disorders. We
      investigated these issues by examining the extent that labour market conditions
      were associated with change in labour force activity among people with anxiety
      disorders, affective disorders, and schizophrenia, in comparison to healthy
      working age adults. METHODS: Data files were provided by the Australian Bureau of
      Statistics (ABS) from a population survey conducted in 1998 and replicated in
      2003. Multi-stage probability samples were obtained in 1998 (N(1) = 37,580) and
      2003 (N(2) = 36,088). Adults with schizophrenia, depression, and anxiety
      disorders were compared to healthy working age adults. RESULTS: Greater labour
      demand in 2003 was positively associated with increased labour force
      participation among healthy adults. The proportions actively looking for work
      declined among healthy adults and among those with anxiety disorders. Full-time
      employment significantly increased among healthy working age residents. The
      proportions employed part-time significantly increased in all groups except among
      people with schizophrenia. CONCLUSION: These results support policies which
      remove disincentives and increase access to the more intensive evidence-based
      employment programs even when labour market conditions are improving.

PMID- 18726534
TI  - Psychological distress, depression and generalised anxiety in Turkish and
      Moroccan immigrants in Belgium: a general population study.
AB  - BACKGROUND: This study assesses the prevalence of and risk and protective factors
      for common mental health complaints in a general population sample of Turkish and
      Moroccan immigrants living in Belgium. Focus is on between- and within-group
      variation. METHODS: The study is based on pooled data from the Belgian Health
      Interview Surveys 2001 and 2004 and focuses on the Turkish and Moroccan immigrant
      population aged 18-65 (N = 147 Turks, N = 359 Moroccans). Mental health status is
      assessed with the General Health Questionnaire-12 and the Symptom Checklist 90-R
      subscales for depression and generalised anxiety. Risk and protective factors
      considered are gender, age, household type, labor market position, educational
      level, household income, homeownership, being foreign- or native born and social
      support. RESULTS: Between-group variance was not significant. Within-group
      analysis showed significant effects of gender and social support. Although not
      significant, the results suggested positive associations between social adversity
      and mood status. In addition, there was a tendency for higher risks for
      psychological distress, depression and generalised anxiety in foreign-born as
      compared to Belgian-born Turkish and Moroccan immigrants.

PMID- 18726536
TI  - Responses of a free-living marine nematode community to mercury contamination:
      results from microcosm experiments.
AB  - A microcosm experiment was used to examine the effects of mercury contamination
      on a free-living nematode community in a Tunisian lagoon. Sediments were
      contaminated with three mercury concentrations (low, 0.084 ppm; medium, 0.167
      ppm; and high, 0.334 ppm), and effects were examined after 60 days. Results from
      multiple-comparison tests showed significant differences between nematode
      assemblages from undisturbed control and those from mercury treatments. Most
      univariate measures decreased significantly with increasing level of Hg
      contamination. Results from multivariate analyses of the species abundance data
      demonstrated that responses of nematode species to mercury contamination were
      varied: Araeolaimus bioculatus was eliminated at all the mercury doses tested and
      seemed to be an intolerant species to mercury contamination; Marylynnia
      stekhoveni increased at low and medium concentrations and appeared to be an
      "opportunistic" species at these doses, whereas Prochromadorella neapolitana,
      which increased at all doses tested (0.084, 0.167, and 0.334 ppm), seemed to be a
      "mercury-resistant" species.

PMID- 18726537
TI  - First evidence of altered immune responses and resistance to air exposure in the
      clam Chamelea gallina exposed to benzo(a)pyrene.
AB  - Effects of benzo(a)pyrene [B(a)P] (at a nominal concentration of 0.5 mg/L) on
      immune responses of the clam Chamelea gallina were investigated after 1, 7, and
      12 days exposure. Total hemocyte count (THC), hemocyte volume, phagocytic
      activity, lysozyme-like activity in both hemocyte lysate (HL) and cell-free
      hemolymph (CFH) were measured. As unexpected alterations in hemocyte adhesion
      capability were observed in short-term hemocyte cultures for phagocytosis assays
      after a 1-day exposure, an adhesion test (not included in the original
      experimental setup) was performed after 7 and 12 days of exposure only. The
      survival-in-air test was carried out to evaluate general stress conditions in
      B(a)P-exposed clams. No alterations in THC was observed, whereas exposure for 7
      and 12 days to B(a)P significantly decreased phagocytic activity and adhesion
      capability when compared with controls. Significant decreases in lysozyme
      activity were observed in CFH and HL, with respect to controls. B(a)P was also
      shown to alter the resistance to air exposure of clams. The LT(50) values fell
      from 9 days in control clams to 7 days in 1-day-exposed animals, and from 6 days
      in control clams to 5 days in 7-day-exposed bivalves. No significant variations
      in LT(50) values were recorded after 12 days of exposure. Results highlight a
      relationship between B(a)P exposure and alterations in hemocyte functionality and
      suggest that the contaminant induced irreversible immunosuppression in C.
      gallina, by altering phagocytic activity, adhesion capability, and enzymatic
      activity. Conversely, reduction in resistance to air exposure was reversible,
      suggesting that impairment of important physiological functions of clams occurred
      in the first phases of exposure only.

PMID- 18726538
TI  - Spatial variability of trace metals and inorganic nutrients in surface waters of
      Todos Santos Bay, Mexico in the summer of 2005 during a red tide algal bloom.
AB  - Dissolved and particulate metals (Ag, Cd, Co, Cu, Ni, and Zn) and nutrients
      (PO(4), NO(3), and H(4)SiO(4)) were measured in Todos Santos Bay (TSB) in August
      2005. Two sources producing local gradients were identified: one from a dredge
      discharge area (DDA) and another south of the port and a creek. The average
      concentrations of dissolved Cd and Zn (1.3 and 15.6 nM, respectively) were higher
      by one order of magnitude than the surrounding Pacific waters, even during
      upwelling, and it is attributed to the presence of a widespread and long-lasting
      red tide coupled with some degree of local pollution. A clear spatial gradient
      (10 to 6 pM), from coast to offshore, of dissolved Ag was evident, indicating the
      influence of anthropogenic inputs. The particulate fraction of all metals, except
      Cu, showed a factor of ~3 decrease in concentrations from the DDA to the interior
      of the bay. The metal distributions were related to the bay's circulation by
      means of a numerical model that shows a basically surface-wind-driven offshore
      current with subsurface compensation currents toward the coast. Additionally, the
      model shows strong vertical currents over the DDA. Principal component analysis
      revealed three possible processes that could be influencing the metal
      concentrations within TSB: anthropogenic inputs (Cd, Ag, and Co), biological
      proceses (NO(3), Zn, and Cu), and upwelling and mixing (PO(4), H(4)SiO(4), Cd,
      and Ni). The most striking finding of this study was the extremely high Cd
      concentrations, which have been only reported in highly contaminated areas. As
      there was a strong red tide, it is hypothesized that the dinoflagellates are
      assimilating the Cd, which is rapidly remineralized and being concentrated on the
      stratified surface layers.

PMID- 18726539
TI  - Effects of copper sulfate on growth, development, and escape behavior in Epidalea
      calamita embryos and larvae.
AB  - Epidalea calamita embryos at Gosner stages 3 and 19, and larvae at Gosner stage
      25, were exposed to different copper sulfate concentrations, ranging from 0.05 to
      0.40 mg Cu L(-1), in 96-h acute toxicity tests. Embryonic and larval mortality,
      development, growth, and larval escape behavior were evaluated. LC(50) at 96 h
      obtained at Gosner stages 3, 19, and 25 were 0.22, 0.08, and 0.11 mg Cu L(-1),
      respectively. Embryonic and larval developments were delayed after 96 h of copper
      sulfate exposure. Growth was also affected and individuals in control treatments
      grew to twice the size of those exposed to copper concentrations over 0.2 mg Cu
      L(-1) during the experiments initiated at Gosner stage 19. Escape behavior was
      altered after 96 h of copper sulfate exposure; larvae showed shorter distances
      moved and abnormal displacement types. However, after 4 days of recovery process,
      most of the larvae showed normal escape behavior. For amphibians that develop in
      temporary wetlands, increased development time, lower size, and altered escape
      behavior might have repercussions on the number of individuals that can
      successfully complete metamorphosis and, consequently, on recruitment.

PMID- 18726540
TI  - Accumulation of environmental contaminants in wood duck (Aix sponsa) eggs, with
      emphasis on polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans.
AB  - We measured polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), organochlorine
      pesticides, and mercury in wood duck (Aix sponsa) eggs collected near a North
      Carolina (USA) bleached kraft paper mill. Samples were taken a decade after the
      mill stopped using molecular chlorine. Using avian toxic equivalency factors,
      2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TEQ) concentrations were
      1-30 pg/g fresh wet weight in eggs (n = 48) collected near the mill in 2002-2005
      and were significantly higher than those from a reference site (<1 pg/g) 25 km
      away. Geometric mean wood duck egg TEQs (6 pg/g) were one-fifth those measured at
      this site prior to the cessation of molecular chlorine bleaching. Concentrations
      of mercury in wood duck eggs from nests of the Roanoke River sites ranged from
      0.01 to 0.14 microg/g (geometric mean, 0.04 microg/g) and were significantly
      higher than those from the reference site, where concentrations did not exceed
      0.04 microg/g (geometric mean, 0.02 mug/g). All concentrations were lower than
      those associated with adverse effects in birds. The congener profiles, lack of
      contamination in reference site eggs, and decline in contaminant concentrations
      after process changes at the mill provide strong evidence that mill discharges
      influenced contamination of local wood duck eggs. Collectively, the results
      indicate that the wood duck is an effective sentinel of the spatial and temporal
      extent of PCDD, PCDF, and mercury contamination.

PMID- 18726541
TI  - Total and methyl mercury concentrations in seabird feathers and eggs.
AB  - Seabirds are used frequently as indicators of mercury contamination in marine
      ecosystems, but few studies have examined the forms of mercury found in seabird
      tissues. Here we compare concentrations of total and organic mercury in feathers
      (n=5) of six sympatric nesting seabirds and in egg components of Leach's storm
      petrels from Machias Seal Island, New Brunswick, Canada, during the 2006 breeding
      season. Essentially all (82-133%) mercury found in seabird feathers and egg
      components was methyl mercury, with no interspecific differences in percentage
      methyl mercury. This pattern is consistent with the hypothesis that feather-molt
      and egg production eliminate toxic methyl mercury, while inorganic forms from
      demethylation in the liver remain in internal tissues. Additional studies across
      more species, and comparisons with percentage methyl mercury in internal tissues,
      are required to validate this theory.

PMID- 18726542
TI  - Bronchial anatomy of left lung: a study of multi-detector row CT.
AB  - Familiarity with prevailing pattern and variations in the bronchial tree is not
      only essential for the anatomist to explain bronchial variation in bronchial
      specimens, but also useful for guiding bronchoscopy and instructing pulmonary
      segmental resection. The purpose of this study was designed to demonstrate
      various branching patterns of left lung with 3D images, with special attention
      given to identify the major types at transverse thin-section CT. Two hundred and
      sixteen patients with routine thorax scans were enrolled. The images of bronchial
      tree, virtual bronchoscopy were reconstructed using post-processing technique of
      multi-detector row CT. We attempted to classify the segmental bronchi by
      interpreting the post-processing images, and identified them in transverse thin
      section CT. Our results showed that the segmental bronchial ramifications of the
      left superior lobe were classified into three types mainly, i.e., common stem of
      apical and posterior segmental bronchi (64%, 138/216); trifurcation (23%,
      50/216); common stem of apical and anterior segmental bronchi (10%, 22/216), and
      they could be identified at two typical sections of transverse thin-section CT.
      There were two major types in left basal segmental bronchi, i.e., bifurcation
      (75%, 163/216), trifurcation (18%, 39/216), and they could also be identified at
      two typical sections of transverse thin-section CT. In conclusion, our study have
      offered simplified branching patterns of bronchi and demonstrated various unusual
      bronchial branching patterns perfectly with 3D images, and have also revealed how
      to identify the main branching patterns in transverse thin-section CT.

PMID- 18726543
TI  - Anatomo-histological analysis of the juncturae and their relations to the
      extensor tendons to the dorsum of the hand.
AB  - The juncturae tendinum (JT) may coordinate the extension of hand, force
      redistribution and the stabilization of the metacarpophalangeal joint. The JT
      were studied for their gross appearance, shape, thickness, location and
      histological examination with the dorsum of the hand in 54 cadavers. The JT were
      identified into three groups according to their anatomo-histological features.
      The type 1 was observed in 57.4% of the cases in the second IMC and in 16.7% of
      the cases in the third IMC. The type 2 was detected in 3.7% of the cases in the
      second IMC and in 59.3% of the cases in the third IMC space. The type of 3Y was
      accounted for 14.8% JT in the third IMC space and 53.7% JT in the fourth space.
      The type of 3r was found in 5.55% of the cases in the third IMC and in 37% of the
      cases in the fourth IMC space. In the histologic examination, the fibers of types
      1 and 2 JTs were straight. Type 3 JTs were composed of regularly oriented
      parallel and crosswise bundles of tendineous tissue. This study is important in
      terms of giving accurate knowledge on the anatomo-histological analysis of the
      JTs and their relations to the extensor tendons to the dorsum of the hand. An
      understanding of the structures of the JTs and the interactions between the
      tendons of the fingers is of utmost importance in hand assessment, during the
      reconstructive procedures such as considering the tendons to be transferred.

PMID- 18726544
TI  - Effects of cholinesterase inhibitors on rat nicotinic receptor levels in vivo and
      in vitro.
AB  - Cholinesterase inhibitors (ChEIs) are the mainstay of treatment for AD but differ
      by secondary mechanisms of action. We determine the effects of sub-chronic dosing
      of ChEIs on alpha7 and non-alpha7 nAChRs and determine if differences can be
      observed between them. Sprague-Dawley rats were administered donepezil,
      galantamine; rivastigmine at two doses each, in saline SQ twice daily or with
      nicotine (0.4 mg/kg) as a positive control. After 14 days the animals were
      sacrificed, and the levels of nAChRs were measured using [3H]-EPI to measure non
      alpha7 nAChRs and [3H]-MLA to measure alpha7 nAChRs. In the cortex, all compounds
      tested at the higher doses significantly increased the levels of both [3H]-EPI
      and [3H]-MLA. In the hippocampus all compounds significantly increased [3H]-EPI
      but had no effect on [3H]-MLA binding. No effects were observed in the striatum
      with treatment. There were no differences observed among the ChEIs. In cell
      cultures, none of the ChEIs increased non-alpha7 or alpha7 receptor binding.
      Treatment with ChEIs result in similar increases in receptor levels which suggest
      that the increases in nAChRs may be due simply to the increases in synaptic
      levels of acetylcholine.

PMID- 18726545
TI  - Attention and amygdala activity: an fMRI study with spider pictures in spider
      phobia.
AB  - Facilitated detection of threatening visual cues is thought to be adaptive. In
      theory, detection of threat cues should activate the amygdala independently from
      allocation of attention. However, previous studies using emotional facial
      expressions as well as phobic cues yielded contradictory results. We used fMRI to
      examine whether the allocation of attention to components of superimposed spider
      and bird displays modulates amygdala activation. Nineteen spider-phobic women
      were instructed to identify either a moving or a stationary animal in briefly
      presented double-exposure displays. Amygdala activation followed a dose-response
      relationship: Compared to congruent neutral displays (two birds), amygdala
      activation was most pronounced in response to congruent phobic displays (two
      spiders) and less but still significant in response to mixed displays (spider and
      bird) when attention was focused on the phobic component. When attention was
      focused on the neutral component, mixed displays did not result in significant
      amygdala activation. This was confirmed in a significant parametric graduation of
      the amygdala activation in the order of congruent phobic displays, mixed displays
      with attention focus on the spider, mixed displays with focus on the bird and
      congruent neutral displays. These results challenge the notion that amygdala
      activation in response to briefly presented phobic cues is independent from
      attention.

PMID- 18726546
TI  - Modification of adenovirus type 5 tropism for a preferential transduction of
      human papillomavirus-positive cancer cells.
AB  - Human group C adenoviruses can infect many cell types, and this is due to the
      widespread expression of their receptor, the coxsackievirus and adenovirus
      receptor (CAR). Adenovirus vectors for cancer gene therapy could be significantly
      improved if their tropism were restricted to tumor cells. In this work,
      previously identified peptides that target human papillomaviruses (HPV)
      transformed cells were inserted into the HI loop of a non-CAR-binding fiber.
      These modified fiber proteins were able to assemble into adenovirus particles. We
      demonstrated that these modifications ablated the native tropism of adenovirus
      type 5, and these modified adenoviruses were shown to preferentially transduce
      HPV-transformed cell lines.

PMID- 18726547
TI  - The block of intracellular calcium release affects the pollen tube development of
      Picea wilsonii by changing the deposition of cell wall components.
AB  - Two potent drugs, neomycin and TMB-8, which can block intracellular calcium
      release, were used to investigate their influence on pollen tube growth and cell
      wall deposition in Picea wilsonii. Apart from inhibiting pollen germination and
      pollen tube growth, the two drugs largely influenced tube morphology. The drugs
      not only obviously disturbed the generation and maintenance of the tip-localized
      Ca(2+) gradient but also led to a heavy accumulation of callose at the tip region
      of P. wilsonii pollen tubes. Fourier transform infrared (FTIR) spectroscopy
      analysis showed that the deposition of cell wall components, such as carboxylic
      acid, pectins, and other polysaccharides, in pollen tubes was changed by the two
      drugs. The results obtained from immunolabeling with different pectin and
      arabinogalactan protein antibodies agreed well with the FTIR results and further
      demonstrated that the generation and maintenance of the gradient of cross-linked
      pectins, as well as the proportional distribution of arabinogalactan proteins in
      tube cell walls, are essential for pollen tube growth. These results strongly
      suggest that intracellular calcium release mediates the processes of pollen
      germination and pollen tube growth in P. wilsonii and its inhibition can lead to
      abnormal growth by disturbing the deposition of cell wall components in pollen
      tube tips.

PMID- 18726548
TI  - Expansins and coleoptile elongation in wheat.
AB  - Expansins are now generally accepted to be the key regulators of wall extension
      during plant growth. The aim of this study was to characterize expansins in wheat
      coleoptiles and determine their roles in regulating cell growth. Endogenous and
      reconstituted wall extension activities of wheat coleoptiles were measured. The
      identification of beta-expansins was confirmed on the basis of expansin activity,
      immunoblot analysis, and beta-expansin inhibition. Expansin activities of wheat
      coleoptiles were shown to be sensitive to pH and a number of exogenously applied
      factors, and their optimum pH range was found to be 4.0 to 4.5, close to that of
      alpha-expansins. They were induced by dithiothreitol, K(+), and Mg(2+), but
      inhibited by Zn(2+), Cu(2+), Al(3+), and Ca(2+), similar to those found in
      cucumber hypocotyls. An expansin antibody raised against TaEXPB23, a vegetative
      expansin of the beta-expansin family, greatly inhibited acid-induced extension of
      native wheat coleoptiles and only one protein band was recognized in Western blot
      experiments, suggesting that beta-expansins are the main members affecting cell
      wall extension of wheat coleoptiles. The growth of wheat coleoptiles was closely
      related to the activity and expression of expansins. In conclusion, our results
      suggest the presence of expansins in wheat coleoptiles, and it is possible that
      most of them are members of the beta-expansin family, but are not group 1 grass
      pollen allergens. The growth of wheat coleoptiles is intimately correlated with
      expansin expression, in particularly that of beta-expansins.

PMID- 18726549
TI  - Assistive devices: usage in patients with rheumatoid arthritis.
AB  - We describe the usage of various assistive devices and identify factors
      associated with usage in patients with rheumatoid arthritis (RA). A cross
      sectional, multicentre study was performed in three outpatient rheumatology
      clinics in the Netherlands. Two hundred forty patients with RA participated in
      the study. The main measures were questionnaires and a semi-structured interview
      regarding the possession and usage of 21 common assistive devices in the ISO9999
      categories orthopaedic footwear, personal care, mobility, household and
      adaptations for housing. Potential factors associated with usage included
      sociodemographic variables, health status, quality of life, coping strategies,
      self-efficacy, outcome expectations and satisfaction. Out of 240 patients, 213
      (89%) had one or more assistive devices in possession (median number of devices
      3.0, interquartile range 3.0). The proportions of patients never using a device
      in possession varied between 8% for orthopaedic insoles and 23% for grab bars.
      The main factors related to usage varied among categories, but common
      determinants were a specific impairment or disability, satisfaction with the
      device or related services, self-efficacy and the number of devices in
      possession. In conclusion, in patients with RA, possession rates are high, with
      23% or less of the devices in possession being abandoned. Overall, satisfaction
      rates were high. Factors associated with usage varied among categories and
      comprised, apart from the number of devices in possession and variables related
      to health status, also aspects of satisfaction with the device or related
      services or self-efficacy. The latter findings underline the need for a
      systematic evaluation of the outcomes of assistive devices by prescribing health
      professionals or suppliers in every individual case.

PMID- 18726551
TI  - Abstracts of the 33rd Annual Meeting of the International Urogynecological
      Association. Taipei, Taiwan. September 13-17, 2008.

PMID- 18726550
TI  - The Bath metrology index as assessed by a trained and an untrained rater in
      patients with spondylarthropathy: a study of intra- and inter-rater agreements.
AB  - The Bath ankylosing spondylitis metrology index (BASMI; range 0-10) has gained
      widespread use in daily clinical practice as an objective measure of spinal
      stiffness not only in patients with ankylosing spondylitis (AS) but also in
      patients with other spondylarthropathies (SpA). We examined intra-rater and inter
      rater reproducibility of BASMI scoring in 30 Danish patients with SpA (median age
      40 years, range 22-56 years) fulfilling the European Spondylarthropathy Study
      Group criteria, 25 of them satisfying the modified New York Criteria for AS.
      Measurements were performed twice on two different days (median interval 7 days,
      range 4-11) by a trained physiotherapist (PT) and by an untrained nurse who had
      undergone a single 1-h training session with the PT. The median BASMI score
      obtained by the PT on the two test days was 3.5 (range 1-8) and 3.0 (range 1-8),
      respectively (NS). Test-retest BASMI scores from the PT were significantly
      correlated (r(s) = 0.95, p < 0.0001). The 95% likely range for the difference
      between a patient's BASMI scores from two tests was +/-1.4 corresponding to a
      minimal detectable difference of +/-2 in the individual patient as the scale
      consists of intervals of 1. Similar results were achieved by the nurse. BASMI
      scores obtained by the two raters were significantly inter-correlated (r(s) =
      0.95, p < 0.0001). The mean difference between paired BASMI scores obtained by
      the nurse and the PT on test day 1 was -0.2 with a minimal detectable difference
      of +/-2. A similar result was found using data from test day 2. In conclusion, a
      change in BASMI less than 2 may be due solely to expected random measurement
      error. A single 1-h training session allowed an untrained nurse to obtain BASMI
      results almost identical to those of an experienced PT.

PMID- 18726552
TI  - A point-prevalence study for MRSA in a German university hospital to identify
      patients at risk and to evaluate an established admission screening procedure.
AB  - BACKGROUND: Due to the enormous increase in the number of MRSA-patients, in July
      2004, an extended admission screening protocol was implemented in ICUs and
      surgical wards at Hannover Medical School. PATIENTS AND METHODS: In 2005, a point
      prevalence study (also known as a cross-sectional study) was conducted to
      determine the prevalence of MRSA and Panton-Valentine leukocidin (PVL) among
      inpatients, to identify patients at risk for MRSA colonization and to evaluate
      compliance with admission screening. Inpatients were screened by taking cultures
      from nose, throat and skin lesions. S. aureus isolates were tested for
      antimicrobial susceptibility and PVL. MRSA was analyzed by staphylococcal protein
      A (spa) typing. RESULTS: Of 509 inpatients, 145 (28%) were S. aureus carriers. 27
      (19%) inpatients were MRSA positive, i.e., the MRSA point-prevalence was 5.3%
      (95% CI, 3.49; 7.70). spa type t032 was predominant in 67% of the MRSA
      inpatients. The PVL gene was present in one (0.2%) methicillin-susceptible
      strain. Comparison with data retrieved from the local hospital MRSA database
      showed that, the status of 37% of the MRSA had previously remained undetected
      (10/27). Consequently, MRSA colonization was newly identified in 2.0% (10/509) of
      the patients. Compliance with admission screening failed in three cases.
      Nosocomial acquisition was identified in three patients. Four other patients
      harbouring MRSA were newly identified on wards without routine screening (three
      neurological, one internal medicine ward). CONCLUSION: Despite extended admission
      screening, 37% of all MRSA-positive inpatients were missed. The neurological
      patients were identified as a further risk group and were included in the
      admission screening procedure established.

PMID- 18726553
TI  - Sinus surgery combined with antifungal therapy is effective in the treatment of
      invasive Aspergillus sinusitis in neutropenic patients with cancer.
AB  - BACKGROUND: Invasive Aspergillus sinusitis (IAS) is associated with high
      mortality and poor response to antifungal therapy in patients with hematologic
      malignancies (HM). PATIENTS AND METHODS: We identified 353 patients with invasive
      aspergillosis of whom 39 patients had IAS. Of the 39 patients, 13 underwent sinus
      surgery (SS) in addition to the antifungal therapy, and the remaining 26 control
      patients received antifungal therapy alone. Most patients with IAS had underlying
      leukemia (85%). Both groups had comparable clinical characteristics such as
      gender, age, underlying disease, neutropenia at the onset, persistent
      neutropenia, graft-vs-host-disease, and comparable antifungal therapy. RESULTS:
      Overall response was 7 (53.2%) in the SS group vs 5 (19.2%) in the control group
      (p = 0.06). Among the subgroup of patients with neutropenia at the onset of
      infection, the response rate in the SS group was significantly better than in the
      non-SS group (57% vs 11.8%, respectively; p = 0.028). CONCLUSION: In neutropenic
      patients with IAS and underlying HM, SS significantly improved the response to
      antifungal therapy. Additional studies are warranted.

PMID- 18726554
TI  - Brain abscess due to Panton-Valentine leukocidin-positive Staphylococcus aureus.
AB  - Panton-Valentine leukocidin (PVL) is a cytotoxin produced by Staphylococcus
      aureus that exhibits highly specific lytic activity against polymorphonuclear
      cells, monocytes, and macrophages. A 34-year-old man admitted for right parietal
      brain abscess and thickened dura mater in close proximity to a lytic bone lesion
      is presented. The abscess culture yielded methicillin-sensitive S. aureus that
      produced PVL. The patient did well after surgery and antibiotic treatment. A
      hematogenous infection, route of bone infection with progression to dura mater
      and brain parenchyma was hypothesized. To our knowledge this is the first
      reported case of a brain abscess due to PVL-positive S. aureus.

PMID- 18726555
TI  - Hand infections following penetrating fish fins or bones injuries (FFBI): a
      large, hospital based, retrospective study.
AB  - BACKGROUND: The incidence of hand infections caused by penetrating fish fins or
      bones injuries (FFBI) is likely to increase following worldwide constant growth
      of fishery production and consumption. Because data on these infections are
      scarce, the purposes of this study were to describe their clinical
      characteristics and disease course, and to analyze risk factors for a complicated
      disease course. METHODS: We studied retrospectively all cases of hospitalized
      patients with hand infections following FFBI over the years 1999-2006 in a single
      medical center. Demographic data, underlying diseases, clinical characteristics
      and disease course were analyzed for each case. Univariate and multivariate
      analysis were used for analyzing risk factors for a complicated hospitalization
      course. RESULTS: There were 122 separate episodes of hand infections following
      FFBI among 116 patients, with a mean age (+/- SD) of 52 +/- 19.7. The majority of
      cases were women (51.6%), and they arrived significantly later to the hospital
      after injury. Predisposing conditions (diabetes mellitus, liver disease,
      rheumatologic disorder, malignancy or chronic steroid treatment) were present in
      25% of cases. Most of the cases presented with cellulitis. Cultures of either
      blood or wound were obtained in approximately 1/3 of cases, and 40% of them
      yielded an isolate. Ceftazidime and doxycycline were administered to 68.8% and
      96.7% of cases, respectively. Surgical debridement was performed in 34.4% of
      cases, but there was no case of death or limb amputation. The presence of fever
      (p = 0.0005) and a predisposing condition (p = 0.035) were independently
      correlated with a complicated hospitalization course. CONCLUSIONS: The overall
      prognosis in this largest cohort of hand infections following FFBI was favorable,
      but immune dysfunction carried a complicated course.

PMID- 18726556
TI  - A de novo desmoid tumor of the surgical site following foramen magnum meningioma
      resection in a patient with Gardner's Syndrome: a case report and review of the
      literature.
AB  - BACKGROUND: Gardner's Syndrome is a familial adenomatous polyposis (FAP) syndrome
      that presents with colorectal polyps, craniofacial osteomas, lipomas, epidermoid
      cysts, and ampullary cancers. These patients are at significant risk for
      developing desmoid tumors, which are locally infiltrating fibromatous lesions.
      These are most commonly found in the abdominal cavity, but may be extra
      abdominal. Although FAP-associated desmoid tumors often occur at sites of
      surgical scarring, this is the first report following resection of an
      intracranial meningioma. CASE DESCRIPTION: We present a patient with Gardner's
      Syndrome who underwent resection of a foramen magnum meningioma and subsequently
      developed a de novo desmoid tumor at the surgical site. She had a complete
      surgical resection of the tumor but did not receive adjuvant therapy. At the time
      of her death 7 years after her desmoid tumor resection, she had no evidence of a
      recurrence at the skull base. CONCLUSION: This case report emphasizes the need
      for careful follow-up in patients with Gardner's Syndrome who undergo resection
      of a meningioma or other neurosurgical procedure. Adjuvant therapy may be of
      value in these patients.

PMID- 18726557
TI  - Alternative transcription initiation of the nitrilase gene (BrNIT2) caused by
      infection with Plasmodiophora brassicae Woron. in Chinese cabbage (Brassica rapa
      L.).
AB  - In clubroot disease, gall formation is induced by infection with the obligate
      biotroph Plasmodiophora brassicae, and cell hypertrophy is dependent on increased
      auxin levels. The enzyme nitrilase is suggested to play an important role in
      auxin biosynthesis in plants. Here, we investigated the expression of nitrilase
      genes in clubroot disease in Chinese cabbage (Brassica rapa L.). We isolated four
      isogenes of nitrilase (BrNIT1, BrNIT2, BrNIT3, and BrNIT4) from Chinese cabbage.
      When a BrNIT2-specific probe was used for Northern blot hybridization, enhanced
      accumulation of a 1.4 kb mRNA and additional shorter transcripts (1.1 kb) were
      only detected in clubbed roots 25 days postinoculation (dpi) onward. The
      expression of BrNIT1 was not strongly affected by infection with P. brassicae.
      BrNIT3 expression was detected in the roots at 10 and 20 dpi, and the expression
      was less in clubbed roots than in healthy roots at 20 dpi. Analysis of the
      transcription initiation point of the BrNIT2 gene suggests that 1.1 kb
      transcripts were generated by alternative transcription initiation between the
      second intron and the third exon. The sequence from the second intron to half of
      the third exon (+415 to +1037, 623 bp) had promoter activity in Arabidopsis
      during clubroot formation. Therefore, our results suggest that transcriptional
      regulation of BrNIT2 might be involved in auxin overproduction during clubroot
      development.

PMID- 18726558
TI  - Cross-regulatory mechanisms in hormone signaling.
AB  - Recent studies suggest that hormones act through a web of interacting responses
      rather than through isolated linear pathways. This signal integration
      architecture may be one mechanism for increasing the specificity of outcomes in
      different cellular contexts. Several common themes for cross-regulation between
      pathways can be observed. Here, we propose a classification scheme for different
      levels of signaling pathway cross-regulation. This scheme is based on which parts
      of the individual pathways are acting as information conduits between pathways.
      Examples from the recent plant hormone biology literature are used to illustrate
      the different modes of interaction.

PMID- 18726559
TI  - A putative role for the plasma membrane potential in the control of the
      expression of the gene encoding the tomato high-affinity potassium transporter
      HAK5.
AB  - A chimeric CaHAK1-LeHAK5 transporter with only 15 amino acids of CaHAK1 in the N
      terminus mediates high-affinity K(+) uptake in yeast cells. Kinetic and
      expression analyses strongly suggest that LeHAK5 mediates a significant
      proportion of the high-affinity K(+) uptake shown by K(+)-starved tomato (Solanum
      lycopersicum) plants. The development of high-affinity K(+) uptake, putatively
      mediated by LeHAK5, was correlated with increased LeHAK5 mRNA levels and a more
      negative electrical potential difference across the plasma membrane of root
      epidermal and cortical cells. However, this increase in high-affinity K(+) uptake
      was not correlated with the root K(+) content. Thus, (i) growth conditions that
      result in a hyperpolarized root plasma membrane potential, such as K(+)
      starvation or growth in the presence of NH(4) (+), but which do not decrease the
      K(+) content, lead to increased LeHAK5 expression; (ii) the presence of NaCl in
      the growth solution, which prevents the hyperpolarization induced by K(+)
      starvation, also prevents LeHAK5 expression. Moreover, once the gene is induced,
      depolarization of the plasma membrane potential then produces a decrease in the
      LeHAK5 mRNA. On the basis of these results, we propose that the plant membrane
      electrical potential plays a role in the regulation of the expression of this
      gene encoding a high-affinity K(+) transporter.

PMID- 18726560
TI  - Antibacterial activity of two limonoids from Swietenia mahagoni against multiple
      drug-resistant (MDR) bacterial strains.
AB  - Solvent partitioning followed by column chromatography of the MeOH extract of the
      seeds of Swietenia mahagoni afforded two limonoids, swietenolide (1) and 2
      hydroxy-3-O-tigloylswietenolide (2). The compounds were identified by
      spectroscopic means. The antibacterial activity of these compounds was assessed
      against eight multiple-drug-resistant bacterial strains (clinical isolates) by
      the conventional disc diffusion method. While both compounds were active against
      all test organisms, compound 2 displayed overall more potent activity than
      compound 1.

PMID- 18726561
TI  - Effects of selenium and low levels of lead on mammary tumor development and
      growth in MMTV-infected female mice.
AB  - Selenium (Se) has been demonstrated in previous studies to inhibit mammary
      tumorigenesis in C3H mice infected with the murine mammary tumorvirus, MMTV. The
      antitumorigenic effects of Se in this animal model of breast cancer were
      subsequently shown to be counteracted by Se-antagonistic elements. Lead (Pb), for
      example, was found to abolish the anticarcinogenic effects of Se at 5 ppm in the
      drinking water. The present study was undertaken to explore the effects of Pb at
      just 0.5 ppm in the water, i.e., at a level comparable to the concentrations of
      Pb that have been measured in the tap water of older homes in some communities.
      Groups of 30 female virgin C3H/St mice infected with MMTV maintained on Torula
      yeast-based diets containing either 0.15 or 0.65 ppm of yeast-based organic Se
      and received either deionized water or water containing 0.5 ppm Pb as the acetate
      over their entire postweaning lifespan. In the control group on deionized water
      and the 0.15 ppm Se feed, the tumor incidence was 78.6%, which is normal for this
      strain. Increasing the Se content of the feed to 0.65 ppm lowered the tumor
      incidence to 30%, demonstrating the antitumorigenic effect of Se. In the
      experimental groups, the Pb-exposed mice on the 0.15 ppm Se feed developed signs
      of chronic Pb toxicity as evidenced by diminished weight gain that persisted up
      to the age of 10 months, during which period the animals remained tumor-free.
      Thereafter, weight gains ensued to near the values of the controls, and the
      tumors began to develop in rapid succession until the final tumor incidence of
      73.7% was reached. In the group of mice on the 0.65 ppm Se feed, the toxic
      effects of Pb were diminished, as evidenced by the normal weight gains during the
      first 10 months but with concomitant physiological inactivation of Se, causing
      82.6% of the mice to develop tumors, with the first tumor to appear at the age of
      5 months, 7 months earlier than in the Pb-unexposed controls. In addition, tumor
      growth rates in this group were greatly accelerated and the survival of the tumor
      bearing animals was significantly shortened. Direct evidence for the interactions
      of Pb with Se were obtained by determinations of the two elements in the livers,
      kidneys, and hair of tumor-free and tumor-bearing mice. However, the exposure of
      the mice to Pb in the water also altered the levels of Zn, Cu, Fe, and Cr in the
      organs and tissues, more so in tumor-bearing than tumor-free animals. The present
      study demonstrates the need to consider the interactions of Se with other trace
      elements in discussions of its mechanism of anticarcinogenic action.

PMID- 18726562
TI  - Evaluating sequelae after head and neck cancer from the patient perspective with
      the help of the International Classification of Functioning, Disability and
      Health.
AB  - Functioning is recognized increasingly as an important study outcome with head
      and neck cancer (HNC). The International Classification of Functioning,
      Disability and Health, as adopted by the World Health Organization in 2001, is
      based on a comprehensive bio-psycho-social view. The objective of this study was
      to evaluate functioning from the patient perspective and to classify the results
      using the comprehensive view of the ICF. Patients with HNC were interviewed on
      their problems in daily life using qualitative methodology. Sampling of patients
      followed the maximum variation strategy. Sample size was determined by
      saturation. All individual interviews were digitally recorded and transcribed
      verbatim. Interview texts were divided into meaning units and the concepts
      contained in the meaning units were linked to the ICF according to established
      linking rules. The transcribed data were analyzed and linked by a second health
      professional and the degree of consensus was calculated using kappa statistics.
      Concordance of identified ICF categories among different tumor locations was also
      measured with kappa statistics. Until saturation was reached, 18 patients were
      interviewed: seven patients with oral cancer, five with hypopharyngeal cancer and
      six with laryngeal cancer. Thousand four hundred and sixty-two (1,462) different
      concepts were translated into the ICF using 104 different, second-level ICF
      categories. These ICF categories are presented in detail. From the patient
      perspective, the ICF components (a) Body functions, (b) Activities and
      participation and (c) contextual Environmental factors are equally represented,
      while (d) Body structures show by far the least number of categories. The
      concordance between different tumor locations rages between 0.53 and 0.58
      (confidence interval 0.42-0.70). The degree of consensus in the linking process
      was 0.58 (confidence interval 0.45-0.73). The ICF classification can display
      problems with functioning following HNC sufficiently. For patients with HNC Body
      functions, Activities and participation in every-day life and contextual
      Environmental factors are equally relevant. Therefore, rehabilitation of these
      patients must not confine itself to anatomical and (patho-) physiologic changes,
      but should move towards a more comprehensive view including the individual
      patient's demands on daily life and the given individual contextual
      circumstances.

PMID- 18726563
TI  - Dehydroepiandrosterone (DHEA) prevents the prostanoid imbalance in mesenteric bed
      of fructose-induced hypertensive rats.
AB  - BACKGROUND: In previous studies we reported an altered prostanoid (PR) release
      pattern in mesenteric vessels in fructose (F)-overloaded rats, an experimental
      model of insulin resistance and hypertension. Dehydroepiandrosterone (DHEA) and
      its precursor Dehydroepiandrosterone sulfate (DHEA-S) are the most abundant
      circulating steroid hormones produced by the adrenal and recent studies in both
      cells and animals suggest that DHEA may have acute non-genomic actions that mimic
      both metabolic and vascular actions of insulin. AIM OF THE STUDY: This study was
      to analyze in F-overloaded rats, the effects of DHEA treatment on arterial blood
      pressure and the PR production in mesenteric vessels and aorta. METHODS: Male 6
      week-old Sprague-Dawley rats were randomly divided in four groups: a control
      group (C), a DHEA (30 mg/kg/sc/48 h)-treated group (D), a fructose (10% w/v in
      drinking water)-fed group (F), and both treatments simultaneously group (FD). The
      systolic blood pressure (SBP) was measured by tail cuff method and glycemia and
      triglyderidemia were measured by enzymatic assays. The mesenteric beds of all
      groups were dissected, and incubated in Krebs solution. The PR released were
      measured by HPLC. RESULTS: F overload increased SBP and triglyceridemia and
      decreased the mesenteric vasodilatory PR release. DHEA treatment prevented the
      increment in SBP and triglyceridemia and decreased vasoconstrictor PR in F
      treated rats. CONCLUSION: DHEA normalize the PGI(2)/TX ratio, diminished in F
      overloaded rats, through the decrease in thromboxane (TX) production and this
      could be one of the mechanisms by which DHEA prevented the slight hypertension in
      F-animals.

PMID- 18726564
TI  - Increased dietary cholesterol does not increase plasma low density lipoprotein
      when accompanied by an energy-restricted diet and weight loss.
AB  - BACKGROUND: Diets enriched with dietary cholesterol, frequently from eggs, have
      been shown to produce a small but variable increase in plasma low density
      lipoprotein (LDL) cholesterol. There is evidence to suggest that energy
      restricted diets, that may contain a relatively high proportion of fat and
      cholesterol, can attenuate the cholesterol-raising effect of dietary cholesterol
      on plasma LDL. AIM OF THE STUDY: To determine the combined effects of increased
      dietary cholesterol and weight loss produced by energy restriction on plasma LDL
      cholesterol and lipoproteins. METHODS: A randomized, controlled, parallel study
      was performed in two groups of free-living volunteers on an energy-restricted
      diet for 12 weeks, one group was instructed to consume two eggs a day (n = 24),
      the other, to exclude eggs (n = 21). Dietary advice on energy restriction was
      based on the British Heart Foundation guidelines on how to lose weight for men
      and women. RESULTS: Energy intake fell by 25 and 29% in the egg-fed and non-egg
      fed groups, resulting in a moderate weight loss of 3.4 kg (P < 0.05) and 4.4 kg
      (P < 0.05), respectively. The daily intake of dietary cholesterol increased
      significantly in the egg-fed group from 278 to 582 mg after 6 weeks. The
      concentration of plasma LDL cholesterol decreased in the non-egg-fed groups after
      6 weeks (P < 0.01) and in the egg-fed and non-egg-fed at 12 weeks relative to
      baseline. There were no other significant changes in plasma lipoproteins or LDL
      particle size. CONCLUSIONS: An increased intake of dietary cholesterol from two
      eggs a day, does not increase total plasma or LDL cholesterol when accompanied by
      moderate weight loss. These findings suggest that cholesterol-rich foods should
      not be excluded from dietary advice to lose weight on account of an unfavorable
      influence on plasma LDL cholesterol.

PMID- 18726565
TI  - Peptide-based drug design: here and now.
AB  - After many years of stagnation, peptide therapeutics once again became the focus
      of innovative drug development efforts backed up by venture funds and
      biotechnology companies. Designer peptide drugs overcome the unattractive
      pharmacological properties of native peptides and protein fragments and
      frequently feature nonnatural amino acid or backbone replacements, cyclic or
      multimeric structures, or peptidic or nonpeptidic delivery modules. With their
      high specificity and low toxicity profile, biologicals offer viable alternatives
      to small molecule therapeutics. The development of peptide drugs requires
      specific considerations of this family of biopolymers. Historically, peptide
      vaccines to viral infections and antibacterial peptides led the way in clinical
      development, but recently many other diseases have been targeted, including the
      big sellers AIDS, cancer, and Alzheimer's disease. This book gives practical
      advice to the most important steps in peptide-based drug development such as
      isolation, purification, characterization, interaction with targets, structural
      analysis, stability studies, assessment of biodistribution and pharmacological
      parameters, sequence modifications, and high throughput screening. This brief
      overview provides historical background for each of the listed techniques and
      diseases.

PMID- 18726566
TI  - Strategies for the discovery, isolation, and characterization of natural
      bioactive peptides from the immune system of invertebrates.
AB  - Intensive research efforts for developing new anti-infectious drugs for human
      health rely mostly on technological advancements in high-throughput screening of
      combinatorial chemical libraries and/or natural libraries generated from
      animal/plant extracts. However, nature has done a fascinating job engineering its
      own mutational program through evolution. This results in an incredible diversity
      of natural bioactive molecules that may represent a starting matrix for
      developing new generations of therapeutics of commercial promise to control
      infectious diseases. Among the natural bioactive molecules, peptides are opening
      promising perspectives. The search for novel bioactive peptides for therapeutic
      development relies mainly on a conventional approach driven by a desired
      biological activity followed by the purification and structural characterization
      of the bioactive molecule. Nevertheless, this strategy requires large quantities
      of biological material for activity screening and is thus restrained to animal
      species of large size or that are widely distributed. During the past 10 years,
      thanks to the technological improvements of mass spectro-metry (MS) and liquid
      chromatography, highly sensitive approaches have been developed and integrated
      into the drug-discovery process. We have used several of these sensitive
      biochemical technologies to isolate and characterize defense/immune peptides from
      tiny invertebrates (essentially arthropods) and to limit investigations on a
      restricted number of individuals. These defense/immune peptides, which are mostly
      cationic molecules with a molecular mass often below 10 kDa, are the natural
      armamentarium of the living organisms, and they represent good starting matrices
      for optimization prior their development as future anti-infectious therapeutics.

PMID- 18726567
TI  - Sequence analysis of antimicrobial peptides by tandem mass spectrometry.
AB  - The emergence of new diseases as well as the increasing resistance of bacteria
      against antibiotics over the past decades has become a growing threat for humans.
      This has driven a sustained search for new agents that possess antibacterial
      activities against bacteria being resistant against conventional antibiotics and
      prompted an interest in short to medium-sized peptides called antimicrobial
      peptides (AMPs). Such peptides were isolated from different species, including
      mammals, insects, birds, fish, and plants. As these peptides circulate only at
      low concentrations in body fluids, a multidimensional purification strategy is
      obligatory to obtain pure peptides. The resulting low peptide amounts require
      highly sensitive analytical techniques to sequence the peptides, such as Edman
      degradation or mass spectrometry. Here we describe the protocols used routinely
      in our laboratory to identify peptides with antimicrobial activities by mass
      spectrometry including de novo sequence analysis.

PMID- 18726568
TI  - The spot technique: synthesis and screening of peptide macroarrays on cellulose
      membranes.
AB  - Peptide arrays are a widely used tool for drug development. For peptide-based
      drug design it is necessary to screen a large number of peptides. However, there
      are often difficulties with this approach. Most common peptide synthesis
      techniques are able to simultaneously synthesize only up to a few hundred single
      peptides. Spot synthesis is a positionally addressable, multiple synthesis
      technique offering the possibility of synthesizing and screening up to 10,000
      peptides or peptide mixtures on cellulose or other membrane surfaces. In this
      chapter we present the basic procedures and screening methods related to spot
      synthesis and outline protocols for easy-to-use detection methods on these
      peptide arrays.

PMID- 18726569
TI  - Analysis of Abeta interactions using ProteinChip technology.
AB  - Abeta peptides are now acknowledged to play a central role in the pathogenesis of
      Alzheimer's disease. Their generation results from the sequential cleavage of
      amyloid precursor protein by beta and gamma secretases. The resulting peptide
      fragments impart toxicity via their ability to form soluble oligomers and bind to
      cell membranes. In this chapter we describe the use of ProteinChip technology to
      study the physicochemical behaviour of Abeta and its mechanisms of toxicity.
      These include analyzing (1) Abeta processing and quantitation of peptide
      fragments, (2) Abeta aggregation and the quantitation of oligomers, and (3) Abeta
      lipid interactions.

PMID- 18726570
TI  - NMR in peptide drug development.

PMID- 18726571
TI  - Molecular dynamics simulations of peptides.

PMID- 18726572
TI  - Short linear cationic antimicrobial peptides: screening, optimizing, and
      prediction.
AB  - The problem of pathogenic antibiotic-resistant bacteria such as Staphylococcus
      aureus and Pseudomonas aeruginosa is worsening, demonstrating the urgent need for
      new therapeutics that are effective against multidrug-resistant bacteria. One
      potential class of substances is cationic antimicrobial peptides. More than 1000
      natural occurring peptides have been described so far. These peptides are short
      (less than 50 amino acids long), cationic, amphiphilic, demonstrate different
      three-dimensional structures, and appear to have different modes of action. A new
      screening assay was developed to characterize and optimize short antimicrobial
      peptides. This assay is based on peptides synthesized on cellulose, combined with
      a bacterium, where a luminescence gene cassette was introduced. With help of this
      method tens of thousands of peptides can be screened per year. Information gained
      by this high-throughput screening can be used in quantitative structure-activity
      relationships (QSAR) analysis. QSAR analysis attempts to correlate chemical
      structure to measurement of biological activity using statistical methods. QSAR
      modeling of antimicrobial peptides to date has been based on predicting
      differences between peptides that are highly similar. The studies have largely
      addressed differences in lactoferricin and protegrin derivatives or similar de
      novo peptides. The mathematical models used to relate the QSAR descriptors to
      biological activity have been linear models such as principle component analysis
      or multivariate linear regression. However, with the development of high
      throughput peptide synthesis and an antibacterial activity assay, the numbers of
      peptides and sequence diversity able to be studied have increased dramatically.
      Also, "inductive" QSAR descriptors have been recently developed to accurately
      distinguish active from inactive drug-like activity in small compounds.
      "Inductive" QSAR in combination with more complex mathematical modeling
      algorithms such as artificial neural networks (ANNs) may yield powerful new
      methods for in silico identification of novel antimicrobial peptides.

PMID- 18726573
TI  - Investigating the mode of action of proline-rich antimicrobial peptides using a
      genetic approach: a tool to identify new bacterial targets amenable to the design
      of novel antibiotics.
AB  - The proline-rich antimicrobial peptides (PRPs) are considered to act by crossing
      bacterial membranes without altering them and then binding to, and functionally
      modifying, one or more specific targets. This implies that they can be used as
      molecular hooks to identify the intracellular or membrane proteins that are
      involved in their mechanism of action and that may be subsequently used as
      targets for the design of novel antibiotics with mechanisms different from those
      now in use. The targets can be identified by using peptide-based affinity columns
      or via the genetic approach described here. This approach depends on chemical
      mutagenesis of a PRP-susceptible bacterial strain to select mutants that are
      either more resistant or more susceptible to the relevant peptide. The genes
      conferring the mutated phenotype can then be isolated and identified by
      subcloning and sequencing. In this manner, we have currently identified several
      genes that are involved in the mechanism of action of these peptides, including
      peptide-transport systems or potential resistance factors, which can be used or
      taken into account in drug design efforts.

PMID- 18726574
TI  - Serum stability of peptides.
AB  - Hospitals worldwide have lately reported a worrying increase in the number of
      isolated drug-resistant pathogenic microbes. This has to some extent fueled at
      least academic interest in design and development of new lead components for
      novel drug design. Much of this interest has been focused on antimicrobial
      peptides and peptides in general, primarily due to their natural occurrence and
      low toxicity. However, issues have been raised regarding the stability of peptide
      therapeutics for systemic use. The focus of this chapter is assays for measuring
      peptide stability in the presence of serum, both in vitro and in vivo.

PMID- 18726575
TI  - Preparation of glycosylated amino acids suitable for Fmoc solid-phase assembly.
AB  - Many biological interactions and functions are mediated by glycans, consequently
      leading to the emerging importance of carbohydrate and glycoconjugate chemistry
      in the design of novel drug therapeutics. Despite the challenges that
      carbohydrate moieties bring into the synthesis of glycopeptides and
      glycoproteins, considerable progress has been made during recent decades.
      Glycopeptides carrying many simple glycans have been chemically synthesized,
      enzymatic approaches have been utilized to introduce more complex glycans, and
      most recently native chemical ligation has enabled synthesis of glycoproteins
      from well-designed peptide and glycopeptide building blocks. Currently, general
      synthetic methodology for glycopeptides relies on preformed glycosylated amino
      acids for the stepwise solid-phase peptide synthesis. The formation of glycosidic
      bonds is of fundamental importance in the assembly of glycopeptides. As such,
      every glycosylation has to be regarded as a unique problem, demanding
      considerable systematic research. In this chapter we will summarize the most
      common chemical methods for the stereoselective synthesis of N- and O
      glycosylated amino acids. The particular emphasis will be given to the
      preparation of building blocks for use in solid-phase glycopeptide synthesis
      based on the 9-fluorenylmethoxycarbonyl (Fmoc) protective group strategy.

PMID- 18726576
TI  - Synthesis of O-phosphopeptides on solid phase.
AB  - Most mammalian proteins are transiently phosphorylated on seryl, threonyl, or
      tyrosyl positions by kinases and dephosphorylated by phosphatases in response to
      specific intra- or extracellular signals. Many diseases, such as cancer, are
      caused by altered kinase and phosphatase activities or changed expression levels
      of either of these enzymes. Thus phosphopeptides are important and universal
      tools to study disease-specific changes, such as protein-protein/DNA interactions
      or hyperactive kinases, using phosphopeptides or the corresponding mimics. Here
      we describe two generally applicable techniques to synthesize multiply
      phosphorylated peptides as basic tools for drug development. The phosphopeptides
      were purified to homogeneity and characterized by mass spectrometry.

PMID- 18726577
TI  - Peptidomimetics: Fmoc solid-phase pseudopeptide synthesis.
AB  - Peptidomimetic modifications or cyclization of linear peptides are frequently
      used as attractive methods to provide more conformationally constrained and thus
      more stable and bioactive peptides. Among numerous peptidomimetic approaches
      described recently in the literature, particularly attractive are pseudopeptides
      or peptide bond surrogates in which peptide bonds have been replaced with other
      chemical groups. In these peptidomimetics the amide bond surrogates possess three
      dimensional structures similar to those of natural peptides, yet with significant
      differences in polarity, hydrogen bonding capability, and acid-base character.
      The introduction of such modifications to the peptide sequence is expected to
      completely prevent protease cleavage of amide bond and significantly improve
      peptides' metabolic stability. In this chapter we consider Fmoc solid-phase
      synthesis of peptide analogs containing the amide surrogate that tend to be
      isosteric with the natural amide. This includes synthesis of peptidosulfonamides,
      phosphonopeptides, oligoureas, depsides, depsipeptides, and peptoids.

PMID- 18726578
TI  - Synthesis of toll-like receptor-2 targeting lipopeptides as self-adjuvanting
      vaccines.
AB  - Effective Th1- and Th2-type immune responses that result in protective immunity
      against pathogens can be induced by self-adjuvanting lipopeptides containing the
      lipid moiety dipalmitoyl-S-glyceryl cysteine (Pam2Cys). The potent immunogenicity
      of these lipopeptides is due to their ability to activate dendritic cells by
      targeting and signaling through Toll-like receptor-2 (TLR-2). In addition, the
      simplicity and flexibility in their design as well as their ease of chemical
      definition and characterisation makes them highly attractive vaccine candidates
      for humans and animals. We describe in this chapter the techniques involved in
      the synthesis of an immunocontraceptive lipopeptide vaccine as well as the
      experimental assays carried out to evaluate its efficiency.

PMID- 18726579
TI  - Synthesis of a multivalent, multiepitope vaccine construct.
AB  - A major challenge to contemporary peptide chemistry is to reproduce highly
      complex active sites or complexes of native proteins. In addition to the need for
      the combination of different peptide fragments, true protein mimics designed for
      therapeutic use frequently require the incorporation of multiple copies of given
      active domains in a biologically relevant spatial arrangement. Perhaps the best
      examples for this line of drug design are subunit vaccine candidates against
      extracellular domains of ion-channel proteins. One of our earlier constructs
      containing four copies of the ectodomain of the M2 protein of influenza virus
      together with two independent T-helper cell epitopes induced protective antibody
      production in mice. Here I describe an improved synthesis of the M2-based
      multiepitope and multivalent peptide construct. In general, the synthetic
      strategy outlined here can serve as a model for the orthogonal N-terminal and
      side-chain-protecting scheme during the preparation of large, complex peptides or
      small, engineered proteins.

PMID- 18726580
TI  - Cysteine-containing fusion tag for site-specific conjugation of therapeutic and
      imaging agents to targeting proteins.
AB  - Targeted delivery of therapeutic and imaging agents requires conjugation of a
      corresponding payload to a targeting peptide or protein. The ideal procedure
      should yield a uniform preparation of functionally active conjugates and be
      translatable for development of clinical products. We describe here our
      experience with site-specific protein modification via a novel cysteine
      containing fusion tag (Cys-tag), which is a 15-amino-acid (aa) N-terminal
      fragment of human ribonuclease I with the R4C substitution. Several Cys-tagged
      proteins and peptides with different numbers of native cysteines were expressed
      and refolded into functionally active conformation, indicating that the tag does
      not interfere with the formation of internal disulfide bonds. We also describe
      standardized procedures for site-specific conjugation of very different payloads,
      such as functionalized lipids and liposomes, radionuclide chelators and
      radionuclides, fluorescent dyes, drug-derivatized dendrimers, scaffold proteins,
      biotin, and polyethyleneglycol to Cys-tagged peptides and proteins, as well as
      present examples of functional activity of targeted conjugates in vitro and in
      vivo. We expect that Cys-tag would provide new opportunities for development of
      targeted therapeutic and imaging agents for research and clinical use.

PMID- 18726581
TI  - [Natural orifice transluminal endoscopic surgery in future obesity treatment].
AB  - The current trend in surgery to minimize access trauma will continue. As
      experience grows, minimally invasive surgical techniques are used increasingly in
      major surgical procedures to treat morbid obesity. Obese patients benefit most
      from its low morbidity for complications. As a result transluminal endoscopic
      surgery via natural orifices (NOTES) is obviously of great interest due to its
      potential in obesity surgery. In NOTES procedures, natural orifices such as the
      transgastric, transvaginal, transcolonic, and transvesical routes are used.
      Possible advantages are faster recovery, less pain, greater patient mobility, no
      hernias, and better cosmesis. Endoscopic intraluminal techniques and sleeve
      gastrectomy are procedures which can be best transferred into NOTES and
      associated techniques. Obesity surgery is an important element of
      gastrointestinal surgery today and has an important future role in our societies.
      Principles of minimal access surgery, as represented by NOTES, will be developed
      further and play a future role in medicine.

PMID- 18726582
TI  - [Ca scoring - standarized or after all individual?].

PMID- 18726583
TI  - Isolation and characterization of a low phytic acid rice mutant reveals a
      mutation in the rice orthologue of maize MIK.
AB  - Using a forward genetics approach, we isolated two independent low phytic acid
      (lpa) rice mutants, N15-186 and N15-375. Both mutants are caused by single gene,
      recessive non-lethal mutations, which result in approximately 75% (N15-186) and
      43% (N15-375) reductions in seed phytic acid (inositol hexakisphosphate). High
      performance liquid chromatography and GC-MS analysis of seed extracts from N15
      186 indicated that, in addition to phytic acid, inositol monophosphate was
      significantly reduced whereas inorganic phosphorus and myo-inositol were greatly
      increased when compared with wild-type. The changes observed in N15-186 resemble
      those previously described for the maize lpa3 mutant. Analysis of N15-375
      revealed changes similar to those observed in previously characterized rice lpa1
      mutants (i.e. significant reduction in phytic acid and corresponding increase in
      inorganic phosphorus with little or no change in inositol phosphate intermediates
      or myo-inositol). Further genetic analysis of the N15-186 mutant indicated that
      the mutation, designated lpa N15-186, was located in a region on chromosome 3
      between the microsatellite markers RM15875 and RM15907. The rice orthologue of
      maize lpa3, which encodes a myo-inositol kinase, is in this interval. Sequence
      analysis of the N15-186 allele of this orthologue (Os03g52760) revealed a single
      base pair change (C/G to T/A) in the first exon of the gene, which results in a
      nonsense mutation. Our results indicate that lpa N15-186 is a mutant allele of
      the rice myo-inositol kinase (OsMIK) gene. Identification and characterization of
      lpa mutants, such as N15-186, will facilitate studies on the regulation of phytic
      acid biosynthesis and accumulation and help address questions concerning the
      contribution of the inositol lipid-dependent and independent biosynthetic
      pathways to the production of seed phytic acid.

PMID- 18726584
TI  - Novel QTLs for photoperiodic flowering revealed by using reciprocal backcross
      inbred lines from crosses between japonica rice cultivars.
AB  - The rice japonica cultivars Nipponbare and Koshihikari differ in heading date and
      response of heading to photoperiod (photoperiod sensitivity). Using simple
      sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers, we
      conducted quantitative trait locus (QTL) analyses for heading date in a set of
      reciprocal backcross inbred lines (BILs) from crosses between Nipponbare and
      Koshihikari. Under natural-day conditions, transgressive segregation in days to
      heading (DTH) toward both early and late heading was observed in both BIL
      populations. QTL analyses revealed that two QTLs--on chromosomes 3 and 6--were
      involved in the difference in heading date between the parental cultivars. The
      Nipponbare allele at the QTLs on chromosomes 3 and 6 showed, respectively,
      increasing and decreasing effects on DTH in both BIL populations. The
      transgressive segregation observed in the BILs could be accounted for mainly by
      the complementary action of a set of alleles with opposing effects. Both QTLs
      were finely mapped as single Mendelian factors in secondary mapping populations
      (BC2F2 plants/BC2F3 lines). The QTL on chromosome 3 was mapped in the 1,140-kb
      interval between 94O03-4 (SSR) and OJ21G19-4 (SNP) and was designated Hd16. The
      QTL on chromosome 6 was mapped in the 328-kb interval between P548D347 (SSR) and
      0007O20 (SSR) and was designated Hd17. Both Hd16 and Hd17 were involved in
      photoperiod sensitivity, as revealed by observation of the DTH of nearly isogenic
      lines of Nipponbare under short- and long-day conditions, suggesting that allelic
      differences in both Hd16 and Hd17 account for most of the difference in
      photoperiod sensitivity between the parental cultivars.

PMID- 18726585
TI  - Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause.
AB  - The metabolic abnormalities of type 2 diabetes can be reversed reproducibly by
      bariatric surgery. By quantifying the major pathophysiological abnormalities in
      insulin secretion and insulin action after surgery, the sequence of events
      leading to restoration of normal metabolism can be defined. Liver fat levels fall
      within days and normal hepatic insulin sensitivity is restored. Simultaneously,
      plasma glucose levels return towards normal. Insulin sensitivity of muscle
      remains abnormal, at least over the weeks and months after bariatric surgery. The
      effect of the surgery is explicable solely in terms of energy restriction. By
      combining this information with prospective observation of the changes
      immediately preceding the onset of type 2 diabetes, a clear picture emerges.
      Insulin resistance in muscle, caused by inherited and environmental factors,
      facilitates the development of fatty liver during positive energy balance. Once
      established, the increased insulin secretion required to maintain plasma glucose
      levels will further increase liver fat deposition. Fatty liver causes resistance
      to insulin suppression of hepatic glucose output as well as raised plasma
      triacylglycerol. Exposure of beta cells to increased levels of fatty acids,
      derived from circulating and locally deposited triacylglycerol, suppresses
      glucose-mediated insulin secretion. This is reversible initially, but eventually
      becomes permanent. The essential time sequence of the pathogenesis of type 2
      diabetes is now evident. Muscle insulin resistance determines the rate at which
      fatty liver progresses, and ectopic fat deposition in liver and islet underlies
      the related dynamic defects of hepatic insulin resistance and beta cell
      dysfunction. These defects are capable of dramatic reversal under hypoenergetic
      feeding conditions, completely in early diabetes and to a worthwhile extent in
      more established disease.

PMID- 18726587
TI  - Wide mass range trapping using a 7-T internal source matrix-assisted laser
      desorption/ionization Fourier transform mass spectrometer.
AB  - A wide mass range trapping experiment using internal source matrix-assisted laser
      desorption-Fourier transform mass spectrometry (MALDI-FTMS) was evaluated. In
      this method, the front trap plate potential is ramped up and the rear trap plate
      potential is simultaneously decreased using a cubic cell to trap ions over a wide
      range of mass-to-charge ratios. To apply this to MS/MS experiments, a second ion
      ejection procedure would remove unwanted ions, with the selected remaining ions
      then fragmented by collision-induced dissociation. In measurements using a 7.2-T
      unshielded magnet presented here, an approximately equimolar mixture of a set of
      poly(ethylene glycol) (PEG) species for the ramped measurements had peak areas of
      1.0:1.0:1.0:1.0, as did the previously described integral method which gave peak
      areas of 1.0:1.1:1.0:1.0, in good agreement with the known composition of the
      samples deposited on the MALDI probe tip. Comparative MALDI-TOF in reflectron
      mode results were of similar quality for the equimolar mixture, giving a ratio of
      1.0:1.0:1.2:0.9. All methods failed to varying degrees when individual PEG
      compositions of the trial mixture were changed. However, the previously described
      integral method showed relatively better results for all but the PEG 8000 doubled
      mixture.

PMID- 18726586
TI  - Colorimetric method for enzymatic screening assay of ATP using Fe(III)-xylenol
      orange complex formation.
AB  - In hygiene management, recently there has been a significant need for screening
      methods for microbial contamination by visual observation or with commonly used
      colorimetric apparatus. The amount of adenosine triphosphate (ATP) can serve as
      the index of a microorganism. This paper describes the development of a
      colorimetric method for the assay of ATP, using enzymatic cycling and Fe(III)
      xylenol orange (XO) complex formation. The color characteristics of the Fe(III)
      XO complexes, which show a distinct color change from yellow to purple, assist
      the visual observation in screening work. In this method, a trace amount of ATP
      was converted to pyruvate, which was further amplified exponentially with coupled
      enzymatic reactions. Eventually, pyruvate was converted to the Fe(III)-XO
      complexes through pyruvate oxidase reaction and Fe(II) oxidation. As the assay
      result, yellow or purple color was observed: A yellow color indicates that the
      ATP concentration is lower than the criterion of the test, and a purple color
      indicates that the ATP concentration is higher than the criterion. The method was
      applied to the assay of ATP extracted from Escherichia coli cells added to cow
      milk.

PMID- 18726588
TI  - Kinetic and kinematic adaptation to anisotropic load.
AB  - Different investigators have proposed that multi-joint arm movements are planned
      with respect to either the path of the hand or the forces and torques acting
      about the moving joints. In this experiment, we examined the kinematic and
      kinetic response of the motor system when a load was applied to the forearm,
      which reduced the natural anisotropy of the arm. We asked two questions: (1) when
      the movement path changes upon the introduction of the novel load, do muscle
      torques at the shoulder and elbow remain the same as they were before the load
      was applied? and (2) when the path is restored partially as the novel load is
      learned, do changes in muscle torque occur preferentially at one or the other
      joint? Participants performed rapid arm movements to a target with and without
      the novel load attached to their arm. Changes in hand path and muscle torque
      profiles were examined immediately after the application of the load and again
      following 30 practice trials. The introduction of the load increased the
      curvature of hand paths for each participant and resulted in changes in the
      magnitude and time course of muscle torque at both joints, although to a greater
      extent at the shoulder. After practice with the load, hand paths and elbow muscle
      torques resembled those produced with no load. Muscle torques produced at the
      shoulder, however, did not return to pre-load patterns. These observations
      provide support for the idea that movements are initiated by planned muscle
      torques and that as the movement proceeds muscle torques are regulated in order
      to produce hand paths that conform approximately to a kinematic plan.

PMID- 18726589
TI  - Distortions of perceived auditory and visual space following adaptation to
      motion.
AB  - Adaptation to visual motion can induce marked distortions of the perceived
      spatial location of subsequently viewed stationary objects. These positional
      shifts are direction specific and exhibit tuning for the speed of the adapting
      stimulus. In this study, we sought to establish whether comparable motion-induced
      distortions of space can be induced in the auditory domain. Using individually
      measured head related transfer functions (HRTFs) we created auditory stimuli that
      moved either leftward or rightward in the horizontal plane. Participants adapted
      to unidirectional auditory motion presented at a range of speeds and then judged
      the spatial location of a brief stationary test stimulus. All participants
      displayed direction-dependent and speed-tuned shifts in perceived auditory
      position relative to a 'no adaptation' baseline measure. To permit direct
      comparison between effects in different sensory domains, measurements of visual
      motion-induced distortions of perceived position were also made using stimuli
      equated in positional sensitivity for each participant. Both the overall
      magnitude of the observed positional shifts, and the nature of their tuning with
      respect to adaptor speed were similar in each case. A third experiment was
      carried out where participants adapted to visual motion prior to making auditory
      position judgements. Similar to the previous experiments, shifts in the direction
      opposite to that of the adapting motion were observed. These results add to a
      growing body of evidence suggesting that the neural mechanisms that encode visual
      and auditory motion are more similar than previously thought.

PMID- 18726590
TI  - Congenital lobar emphysema: appearance on fetal MRI.

PMID- 18726591
TI  - Comparative study and expression analysis of the interferon gamma gene locus
      cytokines in Xenopus tropicalis.
AB  - Using bioinformatics approach, the genome locus containing interleukin (IL)-22,
      IL-26, and interferon gamma (IFN-gamma) genes has been identified in the
      amphibian, Xenopus tropicalis. Like that in other vertebrates such as fish,
      birds, and mammals, the Xenopus IL-22, IL-26, and IFN-gamma are clustered in the
      same chromosome and the adjacent genes are conserved. The genomic structures of
      the Xenopus IL-22, IL-26, and IFN-gamma gene were identical to that of their
      mammalian counterparts. The Xenopus IL-22 and IL-26 genes contained five exons
      and four introns while the Xenopus IFN-gamma gene consisted of four exons and
      three introns. The Xenopus IL-22, IL-26, and IFN-gamma share 14.1-41.6%, 14.6
      31.2%, and 23.7-36.5% identity to their counterparts in other species,
      respectively. Reverse-transcription polymerase chain reaction (PCR) and real-time
      quantitative PCR analyses revealed that the expression of IL-22, IL-26, and IFN
      gamma genes was significantly upregulated after simulation with bacterial
      polyliposaccharide and/or synthetic double-stranded poly(I:C), suggesting these
      cytokines like those in other vertebrates play an important role in regulating
      immune response in Xenopus.

PMID- 18726593
TI  - Multiple myeloma developing after imatinib mesylate therapy for chronic myeloid
      leukemia.

PMID- 18726592
TI  - Positive diversifying selection in avian Mx genes.
AB  - Mx proteins are interferon-induced GTPases that confer antiviral activities
      against RNA viruses. We analysed the molecular evolution of the Mx gene in birds
      using data on interspecific divergence in anseriform and galliform birds, and on
      intraspecific diversity in commercial chicken lines, local Chinese chicken breeds
      as well as in the mallard. The overall ratio of non-synonymous to synonymous
      substitution was unusually high, 0.80, indicating relaxed constraint or positive
      selection. Evidence for the latter was provided by that a total of 11-18 codons
      were found to have evolved under positive selection. The great majority of these
      codons are located in a region unique to birds at the N-terminal end of the Mx
      protein. We found an excess of non-synonymous polymorphisms relative to
      synonymous variants in all comparisons. This, together with positive Tajima's D
      values in the local Chinese chicken breeds and in the mallard suggests that
      balancing selection is acting in avian Mx genes. As such, Mx mimics the major
      histocompatibility complex system, indicating that heterozygous individuals are
      better off withstanding pathogen attack.

PMID- 18726594
TI  - The simultaneous diagnosis of Kaposi sarcoma and MDS RAEB-II in a human
      immunodeficiency virus-negative patient. A rare occurrence.

PMID- 18726595
TI  - [Practical problems in breast screening. Columnar cell lesions including flat
      epithelial atypia and lobular neoplasia].
AB  - Columnar cell lesions (CCL) and lobular neoplasia (LN) are encountered with
      increasing frequency in breast screening biopsies. CCLs are frequently associated
      with microcalcifications, whereas LN is an incidental finding in most cases. Flat
      epithelia atypia (FEA) the atypical variant of CLL, LN and atypical ductal
      hyperplasia (ADH) are frequently associated lesions. Molecular genetic studies of
      CCL, ductal carcinoma in situ (DCIS) and low grade invasive carcinomas revealed
      similar chromosomal alterations supporting the assumption that CCLs are
      neoplastic proliferations. The frequent association of FEA together with well
      differentiated invasive carcinomas provides further evidence of this concept.
      There is no internationally accepted classification of CCLs at present. CDH1-gene
      mutations are the cardinal feature of LN and invasive lobular carcinoma. In
      immunohistochemically CDH1-positive cases, alternative genetic alterations of the
      CDH1 pathway can lead to functional loss of CDH1. In our opinion morphologically
      and immunohistochemically hybrid lesions may represent this group of lobular
      lesions. Recent follow-up data suggest a higher rate of ipsilateral carcinomas in
      patients with previously diagnosed LN. It is currently an open question whether
      FEA and LN are members of a common family of intralobular proliferations, which
      are non-obligatory precursors of a low nuclear grade breast neoplasia family.

PMID- 18726596
TI  - [Central pathology review. Inclusion criterion for clinical studies of ovarian
      carcinomas?].
AB  - Currently histopathological review is not standard practice in clinical studies
      of ovarian carcinomas. Published retrospective analyses as well as own
      unpublished observations have indicated that a certain percentage of study
      patients may have ovarian lesions other than ovarian carcinomas which may be in
      conflict with study inclusion criteria. In this context, the distinction of
      ovarian carcinomas from borderline tumors, ovarian metastases, and sex cord
      tumors has been shown to be a potential pitfall. In cases of incorrect diagnoses,
      non-beneficial morbidity at unnecessary high cost may occur, in other instances,
      more adequate therapeutic modalities might be withheld from a patient. At
      present, the concept of a central histopathology review for patients with ovarian
      carcinomas is being studied prospectively in a translational research project of
      the AGO-Ovar termed "HIstologische STandardisierte Zweitbegutachtung in einem
      Studienkollektiv fortgeschrittener Ovarialkarzinome, OVAR 11t-HISTO"
      (Histological standardized review in a study collective of advanced ovarian
      cancer; http://www.mh-hannover.de/institute/pathologie/dgp:Studien).

PMID- 18726597
TI  - Interstitial lung disease associated with collagen vascular disorders: disease
      quantification using a computer-aided diagnosis tool.
AB  - The purpose of this study was to evaluate a computer-aided diagnosis (CAD) tool
      compared to human observers in quantification of interstitial lung disease (ILD)
      in patients with collagen-vascular disorders. A total of 52 patients with
      rheumatoid arthritis (n=24), scleroderma (n=14) and systemic lupus erythematosus
      (n=14) underwent thin-section CT. Two independent observers assessed the extent
      of ILD (EoILD), reticulation (EoRet) and ground-glass opacity (EoGGO). CAD
      assessed EoILD twice. Pulmonary function tests were obtained. Statistical
      evaluation used 95% limits of agreement and linear regression analysis. CAD
      correlated well with diffusing capacity (DL(CO)) (R= -0.531, P<0.0001) and
      moderately with forced vital capacity (FVC) (R= -0.483, P=0.0008). There was
      close correlation between CAD and the readers (EoILD vs. CAD: R=0.716, P<0.0001;
      EoRet vs. CAD: R=0.69, P<0.0001). Subgroup analysis including patients with
      minimal EoGGO (<15%) strengthened the correlations between CAD and the readers,
      readers and PFT, and CAD and PFT. EoILD by readers correlated strongly with
      DL(CO) (R= -0.705, P<0.0001) and moderately with FVC (R= -0.559, P=0.0002). EoRet
      correlated closely with DL(CO) and moderately with FVC (DL(CO): R= -0.663; FVC: R
      = -0.436; P <or= 0.005). The CAD system is a promising tool for ILD
      quantification, showing close correlation with human observers and physiologic
      impairment.

PMID- 18726598
TI  - Temporary metallic stent placement in the treatment of refractory benign
      esophageal strictures: results and factors associated with outcome in 55
      patients.
AB  - The purpose of this study was to evaluate the effectiveness of temporary metallic
      stenting in 55 patients with treatment-resistant benign esophageal strictures and
      to identify factors associated with clinical outcomes. Under fluoroscopic
      guidance, covered retrievable stents were placed in 55 patients with benign
      esophageal strictures and were removed with retrieval hook 1 week to 6 months
      after placement. Stent placement was successful in all patients, and the mean
      dysphagia score was reduced from 2.8 to 1.3 (p<0.001). The most common
      complications were tissue hyperproliferation (31%), severe pain (24%), and stent
      migration (25%). During follow-up (mean: 38 months), recurrence of the stricture
      necessitating balloon dilation was seen in 38 (69%) of 55 patients. Maintained
      patency rates after temporary stenting at 1, 3, and 6 months and 1, 2, and 4
      years were 58%, 43%, 38%, 33%, 26%, and 21%, respectively. In multivariate
      analysis, length (p=0.003) of the stricture was the only significant factor
      associated with maintained patency after temporary stenting. In conclusion,
      temporary metallic stenting for refractory benign esophageal strictures may be
      effective during the period of stent placement, but is disadvantaged by the high
      recurrence rates after stent removal, particularly in patients with a long length
      of stricture (>7 cm).

PMID- 18726599
TI  - The cisterna chyli: prevalence, characteristics and predisposing factors.
AB  - The purpose of this study was to determine the prevalence and characteristics of
      the cisterna chyli (CC) in a large 3,000-patient cohort and to identify potential
      predisposing factors for the development of a CC. Three thousand consecutive
      contrast-enhanced CT examinations (1,261 women, 1,739 men, mean age 61.0 years)
      of the chest and/or abdomen were included in this retrospective study. Imaging
      characteristics of the CC (size, attenuation, location) were documented as well
      as clinical information (malignant disease, pattern of metastasis). A CC was
      found in 16.1% of the patients with an average volume of 302 microl. The mean
      attenuation was 4.8 Hounsfield units (HU). Twenty percent of the CC showed CT
      densities of 15 HU and higher. Patients with malignancies showed a significantly
      (p < 0.001) higher prevalence of CC (340/1,757, 19.4%) than patients with benign
      conditions (144/1,243, 11.6%). Especially the finding of a large CC (>1,000
      microl) represents an elevated relative risk for malignancy of 1.7 (p = 0.0017).
      We found a significant association between malignant disease and the presence and
      size of a cisterna chyli. Identifying the continuity between the CC and the
      thoracic duct is a safer method to distinguish a CC from retrocrural lymph nodes
      than near-water CT attenuation alone.

PMID- 18726600
TI  - Effect of conductivity changes on the stability of electric signal waveforms in
      dwarf stonebashers (Mormyridae; Pollimyrus castelnaui, P. marianne).
AB  - The dwarf stonebasher sibling species Pollimyrus castelnaui and P. marianne use
      differences in the electric organ discharges (EODs) for species recognition. As
      EOD waveforms are affected by water conductivity changes, the reliability of
      species recognition might be impeded due to natural variability in the
      environment. EODs of P. castelnaui (N = 8) and P. marianne (N = 8) under high
      (250 microS/cm) and low (25 microS/cm) conductivity were recorded and compared.
      Local peaks of the EODs of both species were significantly and predictably
      modified due to the conductivity change but species-specific differences were
      always recognizable. The duration of the EODs was not influenced by the
      conductivity change. Temperature alterations modified the duration in a linear
      relationship, allowing the determination of Q(10) values (1.6 for P. castelnaui's
      and 1.7 for P. marianne's EODs). As the species-specific differences are not
      masked by conductivity effects, EOD discrimination seems to be a reliable species
      recognition mechanism under natural circumstances.

PMID- 18726601
TI  - Developmental changes in the effects of prostaglandin E2 in the chicken ductus
      arteriosus.
AB  - Prostaglandin E(2) (PGE(2)) is the major vasodilator prostanoid of the mammalian
      ductus arteriosus (DA). In the present study we analyzed the response of isolated
      DA rings from 15-, 19- and 21-day-old chicken embryos to PGE(2) and other
      vascular smooth muscle relaxing agents acting through the cyclic AMP signaling
      pathway. PGE(2) exhibited a relaxant response in the 15-day DA, but not in the 19
      and 21-day DA. Moreover, high concentrations of PGE(2) (>or= 3 microM in 15-day
      and >or= 1 microM in 19-day and 21-day DA) induced contraction of the chicken DA.
      The presence of the TP receptor antagonist SQ29,548, unmasked a relaxant effect
      of PGE(2) in the 19- and 21-day DA and increased the relaxation induced by PGE(2)
      in the 15-day DA. The presence of the EP receptor antagonist AH6809 abolished
      PGE(2)-mediated relaxation. The relaxant responses induced by PGE(2) and the beta
      adrenoceptor agonist isoproterenol, but not those elicited by the adenylate
      cyclase activator forskolin or the phosphodiesterase 3 inhibitor milrinone,
      decreased with maturation. High oxygen concentrations (95%) decreased the
      relaxation to PGE(2). The relaxing potency and efficacy of isoproterenol and
      milrinone were higher in the pulmonary than in the aortic side of the DA, whereas
      no regional differences were found in the response to PGE(2). We conclude that,
      in contrast to the mammalian situation, PGE(2) is a weak relaxant agent of the
      chicken DA and, with advancing incubation, it even stimulates TP vasoconstrictive
      receptors.

PMID- 18726603
TI  - RET/GDNF signalling in vagal neural crest-derived neurons of the chick embryo
      cloaca.
AB  - INTRODUCTION: The growth factor, 'Glial cell line-Derived Neurotrophic Factor'
      (GDNF), is involved in the development of enteric ganglia, using the tyrosine
      kinase receptor 'REarranged during Transfection' (RET) to stimulate the
      proliferation and differentiation of neural crest-derived precursor cells. To
      date, the presence of these signalling molecules have not been studied in the
      developing cloaca, thus the aim of this study was to investigate the distribution
      of RET and GDNF, and analyse their co-localisation in vagal-derived neurons of
      the cloaca using quail-chick chimera embryos. MATERIALS AND METHODS: Chicken
      embryos were incubated until the 10-12 somite stage. The vagal neural tube was
      microsurgically ablated in ovo and replaced with the vagal neural tube from age
      matched quail embryos. Quail-chick chimera embryos were harvested at E12, fixed
      and embedded in paraffin wax, and serially sectioned. Immunohistochemistry was
      performed using human natural killer-1 (HNK-1), quail-cell-specific perinuclear
      (QCPN), GDNF and RET antibodies. RESULTS: HNK-1 labelled all ganglia in the
      myenteric and submucosal plexuses of the cloaca, while the quail-specific QCPN
      antibody labelled all ganglia derived from the transplanted quail vagal neural
      tube (Fig. 1, a, b). RET and GDNF were found both co-localised and expressed in
      separate ganglia in the cloaca (Fig. 1, c, d). The majority of QCPN-labelled
      vagal-derived neurons also expressed RET and GDNF. Fig. 1 HNK-1 (a), QCPN (b),
      GDNF (c) and RET (d) immunoreactivity in the chick cloaca at E12. Arrows show
      ganglia displaying co-immunoreactivity for all four antibodies CONCLUSION:
      Results show that GDNF and RET signalling play a major role in ENS development in
      the chick embryo cloaca. We have shown, for the first time, that the majority of
      vagal neural crest-derived neurons co-express RET and GDNF, thus highlighting the
      importance of these signalling factors in cloacal development.

PMID- 18726602
TI  - Gut hormones in relation to body mass and torpor pattern changes during food
      restriction and re-feeding in the gray mouse lemur.
AB  - Potential implications of gut hormones in body mass and torpor and behavioral
      pattern changes induced by an incremental (40 and 80%) calorie restriction (CR)
      in long-days (LD, summer) and short-days (SD, winter) were investigated in gray
      mouse lemurs. Only 80% food-deprived LD and SD animals showed a continuous mass
      loss resulting in a 10 and 15% mass reduction, respectively. Ghrelin levels of
      all food-deprived groups increased by 2.6-fold on average and remained high after
      re-feeding while peptide YY (PYY) levels increased by 3.8-fold only in LD animals
      under 80% CR. In the re-fed SD group, body mass was positively associated with
      ghrelin and negatively associated with PYY, while no correlations were noted in
      the re-fed LD animals. Plasma glucagon-like peptide-1 (GLP-1) increased by 2.9
      fold only in LD food-restricted mouse lemurs and was negatively associated with
      the minimal body temperature. No significant correlations were reported in food
      deprived SD animals. These results suggest that ghrelin, PYY and GLP-1 may be
      related to pre-wintering fattening mechanisms and to the modulation of torpor
      expression, respectively. Such observation clearly warrants further
      investigations, but it opens an interesting area of research in torpor
      regulation.

PMID- 18726604
TI  - Deficient alpha-smooth muscle actin as a cause of functional intestinal
      obstruction in childhood.
AB  - PURPOSE: Most functional intestinal obstruction in childhood is due to defects in
      the enteric innervation. Functional intestinal obstruction due to smooth muscle
      disorders is rare. The aim of this study was to describe four patients with
      functional intestinal obstruction where the only histopathological abnormality
      was deficient, alpha-smooth muscle actin (alpha-SMA) in the circular muscle of
      their small bowel. MATERIALS AND METHODS: Resected intestinal segments from four
      children with functional intestinal obstruction were either snap frozen or
      embedded in paraffin wax, and transversely sectioned. Sections were examined by
      routine H&E staining, AChE and NADPH-diaphorase histochemistry, and
      immunohistochemistry using PGP9.5 and alpha-SMA antibodies. Normal age-matched
      tissue was used as controls. RESULTS: All four patients demonstrated normal
      innervation in the small and large bowel. We observed striking differences in the
      expression of alpha-SMA within the intestinal muscle layers in all four patients.
      There was a markedly decreased level of alpha-SMA in the smooth muscle compared
      to the longitudinal muscle in the small bowel in each patient. All other regions
      of the intestine examined showed normal levels of alpha-SMA, with similar levels
      expressed in both the circular and longitudinal muscles. CONCLUSION: The
      decreased level of alpha-SMA in the smooth muscle of these patients causes a
      serious mechanical defect, thus interfering with normal intestine motility. These
      findings suggest that patients with functional intestinal obstruction should have
      a comprehensive investigation of the intestinal smooth muscle in addition to the
      assessment of the enteric nervous system.

PMID- 18726605
TI  - Management of pulmonary hypertension in congenital diaphragmatic hernia: nitric
      oxide with prostaglandin-E1 versus nitric oxide alone.
AB  - AIM: Prostaglandin-E1 (PGE1) is used at most centers for treating pulmonary
      hypertension (PH) in congenital diaphragmatic hernia (CDH) because it has been
      regarded as effective. The aim of this study was to investigate the role of PGE1
      for treating PH in CDH. METHODS: We reviewed 49 CDH cases with echocardiography
      proven PH. PH was treated with PGE1 and nitric oxide (NO) and high frequency
      oscillatory ventilation (HFOV) from 1997 to 2001 (PG + NO; n = 19) and with NO
      and HFOV from 2002 to 2007 (NO; n = 30). RESULTS: Subject demographics, severity
      of PH, and presence of other anomalies were not significantly different between
      the two groups. In the PG + NO group, 12/19 (63.2%) survived (PG + NO-s) and 7/19
      (36.8%) died (PG + NO-d). In the NO group, 21/30 (70.0%) survived (NO-s) and 9/30
      (30.0%) died (NO-d). Survival rates were not significantly different. In the NO-s
      group, spontaneous closure of the ductus arteriosus (DA) was significantly
      earlier compared with the PG + NO-s group (P < 0.01; 4.0 +/- 0.9 vs. 9.5 +/- 2.2
      days after birth). DA diameters were significantly larger in groups that died
      compared with groups that survived (P < 0.01), and PH persisted in groups that
      died. In the NO-s group, surgery was possible significantly earlier compared with
      the PG + NO-s group (P < 0.01; 3.75 +/- 0.67 vs. 6.12 +/- 0.78 days after birth).
      No NO-s case developed a PH crisis even though PGE1 was not used. Hospital stay
      was significantly shorter in the NO-s group compared with the PG + NO-s group (P
      < 0.05; 39.9 +/- 19 vs. 53.2 +/- 23 days). CONCLUSION: Nitric oxide alone would
      appear to simplify the management of CDH with PH and provide better outcome.

PMID- 18726606
TI  - Immunohistochemical expression of somatostatin type 2A receptor in neuroendocrine
      carcinoma of uterine cervix.
AB  - INTRODUCTION: Somatostatin and its analogues inhibit the growth of various kinds
      of endocrine and exocrine cells via the somatostatin receptor (SSTR). Expression
      of SSTR2A has been reported in many well-differentiated neuroendocrine tumors and
      small numbers of poorly differentiated neuroendocrine carcinomas. SSTR2A-positive
      neuroendocrine tumors may be treatable by SS analogues. Uterine cervical
      neuroendocrine carcinoma is generally associated with poor prognosis. MATERIALS
      AND METHODS: We examined the expression of SSTR2A and other neuroendocrine
      markers [neural cell adhesion molecule (NCAM), chromogranin A, and synaptophysin]
      by immunohistochemical methods in seven neuroendocrine tumors of the uterine
      cervix: five small cell carcinomas and two large cell neuroendocrine carcinomas.
      RESULTS: SSTR2A was expressed in one small cell carcinoma and two neuroendocrine
      large cell carcinomas. The cell membrane of cells in these carcinomas showed
      strong immunohistochemical reactivity for SSTR2A. SSTR2A-positive cases are also
      frequently positive for the expression of chromogranin A. Treatment with SSTR2A
      may be effective for endocrine tumors. The results indicate the usefulness of
      SSTR2A analogs for the treatment of some uterine neuroendocrine carcinomas.

PMID- 18726607
TI  - Term delivery following successful treatment of choriocarcinoma with brain
      metastases, a case report and review of literature.
AB  - BACKGROUND: Cerebral metastases from choriocarcinoma are a poor prognostic
      indicator of outcome in both the World Health Organization and FIGO
      classification systems. Although gestational trophoblastic neoplasia has become
      the most curable of gynecological malignancies, failure rate among "high-risk"
      patients is still high despite of the use of aggressive multidrug regimens. CASE:
      A 27-year-old woman (G(4)P(2)Ab(1)) presented with hemiplegia due to brain
      metastases of choriocarcinoma 1 year after spontaneous abortion. She underwent
      craniotomy and was treated with nine courses of multiple agent etoposide,
      methotrexate, actinomycin- etoposide, and cisplatinum (EMA-EP) regimen combined
      with whole brain irradiation. She delivered a term healthy child 2 years after
      termination of treatment. CONCLUSION: Multiagent EMA-EP chemotherapy and whole
      brain irradiation with craniotomy in selected patients preserves fertility and
      may improve a patient overall prognosis.

PMID- 18726608
TI  - Prevalence of primary dysmenorrhea in young adult female university students.
AB  - OBJECTIVE: To determine the prevalence of primary dysmenorrhea and attitudes and
      behavior toward dysmenorrhea in the female students of an university toward this
      problem. MATERIALS AND METHODS: A total of 1,266 female university students were
      anonymously surveyed by doctors. RESULTS: It was found that mean age of the
      surveyed students was 21.02+/-2.13 years, mean menarche age was 13.3+/-1.4 years,
      and menstruation frequency was 32.58+/-19.8 days. Of the students, 45.3% were
      found to suffer pain in each menstruation, 42.5% in some and 12.2% in none. Of
      those with primary dysmenorrhea, 66.9% were established to take analgesic drugs.
      CONCLUSION: Prevalence of primary dysmenorrhea was found higher than that cited
      in the literature. It was established that although the rate of consultation with
      health professionals about menstruation and related changes was low, use of
      agents known to be effective in primary dysmenorrhea treatment was highly common.

PMID- 18726609
TI  - Higher-order genome organization in platypus and chicken sperm and repositioning
      of sex chromosomes during mammalian evolution.
AB  - In mammals, chromosomes occupy defined positions in sperm, whereas previous work
      in chicken showed random chromosome distribution. Monotremes (platypus and
      echidnas) are the most basal group of living mammals. They have elongated sperm
      like chicken and a complex sex chromosome system with homology to chicken sex
      chromosomes. We used platypus and chicken genomic clones to investigate genome
      organization in sperm. In chicken sperm, about half of the chromosomes
      investigated are organized non-randomly, whereas in platypus chromosome
      organization in sperm is almost entirely non-random. The use of genomic clones
      allowed us to determine chromosome orientation and chromatin compaction in sperm.
      We found that in both species chromosomes maintain orientation of chromosomes in
      sperm independent of random or non-random positioning along the sperm nucleus.
      The distance of loci correlated with the total length of sperm nuclei, suggesting
      that chromatin extension depends on sperm elongation. In platypus, most sex
      chromosomes cluster in the posterior region of the sperm nucleus, presumably the
      result of postmeiotic association of sex chromosomes. Chicken and platypus
      autosomes sharing homology with the human X chromosome located centrally in both
      species suggesting that this is the ancestral position. This suggests that in
      some therian mammals a more anterior position of the X chromosome has evolved
      independently.

PMID- 18726611
TI  - An ultrasound investigation into the morphology of the human abdominal wall
      uncovers complex deformation patterns during contraction.
AB  - The abdominal wall components, specifically muscle and connective tissue, must
      meet and accommodate a wide range of force demands for torso movement, spine
      stabilization, and respiration. It has a composite laminate nature that may lend
      itself to facilitating the required tissue responses. The purpose of this
      exploratory study was to examine the deformations of the abdominal wall
      connective tissues, with a special focus on both the internal oblique aponeurosis
      and the tendinous intersections of the rectus abdominis, using ultrasound
      imaging, during relatively simple contractions of the abdominal musculature.
      There were two main findings of this study: (1) deformations occurred in nearly
      50% of contractions that would be characterized by a simultaneous expansion in
      multiple planes; (2) the laterally generated forces of the oblique and transverse
      muscles transfer a great deal of force across the rectus abdominis muscle and
      sheath, leading to a lateral movement of the rectus muscle during abdominal
      contraction.

PMID- 18726610
TI  - Inflammatory response after phacoemulsification treated with 0.5% prednisolone
      acetate or vehicle.
AB  - PURPOSE: To compare the inflammatory response after phacoemulsification and
      intraocular lens implantation, using postoperative treatment with 0.5%
      prednisolone acetate eye drops or vehicle. DESIGN: A multi-center randomized
      double-masked vehicle-controlled, parallel group phase IV study. METHODS: Sixty
      two eyes of 62 patients undergoing phacoemulsification were examined at five
      German university eye hospitals (Mainz, Heidelberg, Bonn, Erlangen,
      Frankfurt/Main). Patients received either 0.5% prednisolone acetate eye drops
      (group 1) or vehicle eye drop solution (group 2) four times a day until day 2,
      then open-label treatment with 0.5% prednisolone acetate eye drops four times a
      day continued until day 14 for all patients. Postoperative inflammation was
      evaluated by using laser flare photometry. Secondary efficacy variables included
      visual acuity, intraocular pressure, corneal edema, bulbar conjunctival hyperemia
      and ocular discomfort. RESULTS: In group 1, median flare rose from 7.4 photon
      counts/ms preoperatively to 31.0 photon counts/ms at day 1. In group 2, the flare
      increased from 8.6 photon counts/ms preoperatively to 30.5 photon counts/ms at
      day 1. The differences between the groups were not statistically significant. At
      day 3, flare measures were reduced in group 1 but remained fairly unchanged in
      group 2 (20.8 photon counts/ms vs 32.6 photon counts/ms), which was statistically
      significant (p = 0.0055). At day 14, photon counts were comparable in both groups
      (13.0 photon counts/ms vs 11.4 photon counts/ms), respectively. Both groups were
      comparable regarding secondary efficacy variables. CONCLUSIONS: 0.5% prednisolone
      acetate appeared to be significantly more effective as vehicle in controlling
      intraocular inflammation after phacoemulsification; both groups had a similar
      safety profile.

PMID- 18726612
TI  - Anticipatory control of impending postural perturbation in elite springboard
      divers.
AB  - Among athletes, elite springboard divers (ED) should develop an optimal
      anticipatory control of postural stability, as a result of specific training.
      Postural strategies of ED and healthy subjects (HS) while expecting an impending
      perturbation were compared. The mean center of pressure (COP) position was
      analyzed during control quiet stance (cQS) and during anticipatory quiet stance
      (aQS(1-4)), i.e., in expectation of four backward translations of the support
      surface. During cQS, COP position in ED was not significantly different as
      compared to HS. During aQS(1-4,) a significant increase in the mean COP position
      was observed in both groups with ED adopting a more forward inclined vertical
      alignment than HS. In ED specific training may have resulted in a reference frame
      offset in a more anterior direction while expecting an impending perturbation. We
      suggest that leaning more forward may represent a more reliable way of coping
      with predictable perturbations of postural stability.

PMID- 18726613
TI  - The physiological effects of IGF-1 (class 1:Ea transgene) over-expression on
      exercise-induced damage and adaptation in dystrophic muscles of mdx mice.
AB  - Duchenne muscular dystrophy (DMD) is a genetic disorder in which muscle weakness
      and fragility contribute to ongoing muscle degeneration. Although exercise
      induced muscle damage is associated with adaptation that protects normal muscle
      from further damage, exploiting this process to protect dystrophic muscle has
      been avoided for fear of inducing excessive muscle degeneration. However, muscle
      specific over-expression of the class 1:Ea isoform of insulin-like growth factor
      1 (IGF-1) reduces myofibre necrosis in dystrophic mdx mice (a model for DMD) and,
      therefore, may enhance the adaptation process in response to eccentric exercise.
      To test this hypothesis, we evaluated the effect of transgenic class 1:Ea IGF-1
      over-expression on the susceptibility to muscle damage and subsequent adaptation
      in 12-week-old dystrophic mdx and non-dystrophic control mice. Experiments were
      conducted in vivo using a custom-built isokinetic mouse dynamometer to measure
      the deficit in joint torque (indicating muscle damage) after 20 maximal
      lengthening (eccentric) contractions. Adaptation to this damaging exercise was
      evaluated by repeating the protocol 7 days after the initial exercise. The over
      expression of IGF-1 significantly increased the normalised joint torque in non
      dystrophic mice and appeared to ameliorate the muscle weakness in dystrophic
      mice. All mice displayed a marked reduction in the susceptibility to muscle
      damage on day 7; however, this adaptation was unaffected by IGF-1, showing that
      IGF-1 does not protect the dystrophic muscles of adult mdx mice against damage
      resulting from maximal lengthening contractions.

PMID- 18726614
TI  - Functional characterization of key structural genes in rice flavonoid
      biosynthesis.
AB  - Rice is a model system for monocot but the molecular features of rice flavonoid
      biosynthesis have not been extensively characterized. Rice structural gene
      homologs encoding chalcone synthase (CHS), chalcone isomerase (CHI), flavanone 3
      hydroxylase (F3H), flavonoid 3'-hydroxylase (F3'H), dihydroflavonol 4-reductase
      (DFR), and anthocyanidin synthase (ANS) were identified by homology searches.
      Unique differential expression of OsF3H, OsDFR, and OsANS1 controlled by the
      Pl(w) locus, which contains the R/B-type regulatory genes OSB1 and OSB2, was
      demonstrated during light-induced anthocyanin accumulation in T65-Plw seedlings.
      Previously, F3H genes were often considered as early genes co-regulated with CHS
      and CHI genes in other plants. In selected non-pigmented rice lines, OSB2 is not
      expressed following illumination while their expressed OSB1sequences all contain
      the same nucleotide change leading to the T(64) M substitution within the
      conserved N-terminal interacting domain. Furthermore, the biochemical roles of
      the expressed rice structural genes (OsCHS1, OsCHI, OsF3H, and OsF3'H) were
      established in planta for the first time by complementation in the appropriate
      Arabidopsis transparent testa mutants. Using yeast two-hybrid analysis, OsCHS1
      was demonstrated to interact physically with OsF3H, OsF3'H, OsDFR, and OsANS1,
      suggesting the existence of a macromolecular complex for anthocyanin biosynthesis
      in rice. Finally, flavones were identified as the major flavonoid class in the
      non-pigmented T65 seedlings in which the single-copy OsF3H gene was not
      expressed. Competition between flavone and anthocyanin pathways was evidenced by
      the significant reduction of tricin accumulation in the T65-Plw seedlings.

PMID- 18726615
TI  - Natural variation in responsiveness of Arabidopsis thaliana to methyl jasmonate
      is developmentally regulated.
AB  - A number of Arabidopsis thaliana (L.) Heynh ecotypes were assayed for their
      responses to methyl jasmonate in order to determine any natural variation in
      response to this volatile signal. We observed that the regulation of methyl
      jasmonate-induced expression of the vegetative storage proteins VSP1 and VSP2 is
      linked to the developmental stage of the plants. In two ecotypes investigated
      further, Gr-3 and Col-0, it was observed that the VSP1/2 genes became non
      responsive to methyl jasmonate stimulation as the plants progressed to bolt
      formation and flowering. However, the onset of when this transcriptional
      inactivation occurred differed between the two ecotypes, with Col-0 displaying
      still high levels of transcript at the onset of flowering whereas Gr-3 showed no
      induction of VSP1/2 transcription at the same developmental stage. To our
      knowledge, this is the first time that such a pattern of regulation has been
      described for a methyl jasmonate-regulated gene. Moreover, in an F(2) population
      of a cross between these two ecotypes, the trait for 'VSP1/2 methyl jasmonate non
      responsiveness' segregated among individuals, indicating the feasibility of
      mapping the genetic components of this response.

PMID- 18726616
TI  - A germline mutation of the KIF1B beta gene on 1p36 in a family with neural and
      nonneural tumors.
AB  - Recently, the KIF1B beta gene on 1p36, a region commonly deleted in neural crest
      cancers, was found to be a proapoptotic factor for sympathetic precursors. KIF1B
      beta mutations were detected in pheochromocytomas and neuroblastomas, two
      sympathetic lineage tumors, suggesting a role for this gene in cancer. Here, we
      studied five individuals from a three-generation cancer-prone family with a KIF1B
      beta germline variant and seven of their tumors, both of neural crest and
      nonneural origin. Genetic studies including sequencing, copy number analysis and
      fluorescence in situ-hybridization (FISH) showed retention of both KIF1B beta
      alleles in all neural crest-derived tumors in this family, consistent with
      haploinsufficiency or methylation of the wild-type allele. In contrast, the lung
      adenocarcinoma from one mutation carrier had somatic loss of the wild-type allele
      in agreement with a classical two-hit inactivation. Global transcription analysis
      of KIF1B beta mutant pheochromocytomas revealed that these tumors are
      transcriptionally related to pheochromocytomas with RET and NF1 mutations but
      independent from SDH- and VHL-associated tumors. Furthermore, KIF1B beta-mutant
      tumors are uniquely enriched for pathways related to glutamate metabolism and the
      oxidative stress response. Our data start to delineate the signals that are
      disrupted by KIF1B beta dysfunction in pheochromocytomas and suggest that loss of
      this gene may also be permissive to the development of nonneural crest
      malignancies. This may imply the existence of a tissue-specific gene dosage
      requirement for its tumorigenesis.

PMID- 18726617
TI  - Monitoring of fed-batch E. coli fermentations with software sensors.
AB  - Accurate monitoring and control of industrial bioprocess requires the knowledge
      of a great number of variables, being some of them not measurable with standard
      devices. To overcome this difficulty, software sensors can be used for on-line
      estimation of those variables and, therefore, its development is of paramount
      importance. An Asymptotic Observer was used for monitoring Escherichia coli fed
      batch fermentations. Its performance was evaluated using simulated and
      experimental data. The results obtained showed that the observer was able to
      predict the biomass concentration profiles showing, however, less satisfactory
      results regarding the estimation of glucose and acetate concentrations. In
      comparison with the results obtained with an Extended Kalman Observer, the
      performance of the Asymptotic Observer in the fermentation monitoring was
      slightly better.

PMID- 18726618
TI  - Ethanol and acetate production by Clostridium ljungdahlii and Clostridium
      autoethanogenum using resting cells.
AB  - Combined gasification and fermentation technologies can potentially produce
      biofuels from renewable biomass. Gasification generates synthesis gas consisting
      primarily of CO, CO(2), H(2), N(2), with smaller amounts of CH(4), NO(x), O(2),
      C(2) compounds, ash and tars. Several anaerobic bacteria species can ferment
      bottled mixtures of pure synthesis gas constituents. However, there are
      challenges to maintaining culture viability of synthesis gas exposed cells. This
      study was designed to enhance culture stability and improve ethanol-to-acetate
      ratios using resting (non-growing) cells in synthesis gas fermentation. Resting
      cell states were induced in autotrophic Clostridium ljungdahlii cultures with
      minimal ethanol and acetate production due to low metabolic activity compared to
      growing cell production levels of 5.2 and 40.1 mM of ethanol and acetate.
      Clostridium autoethanogenum cultures were not induced into true resting states
      but did show improvement in total ethanol production (from 5.1 mM in growing
      cultures to 9.4 in one nitrogen-limited medium) as well as increased shifts in
      ethanol-to-acetate production ratios.

PMID- 18726619
TI  - Use of response surface methodology for optimizing process parameters for high
      inulinase production by the marine yeast Cryptococcus aureus G7a in solid-state
      fermentation and hydrolysis of inulin.
AB  - The optimization of process parameters for high inulinase production by the
      marine yeast strain Cryptococcus aureus G7a in solid-state fermentation (SSF) was
      carried out using central composite design (CCD), one of the response surface
      methodologies (RSMs). We found that moisture, inoculation size, the amount ratio
      of wheat bran to rice husk, temperature and pH had great influence on inulinase
      production by strain G7a. Therefore, the CCD was used to evaluate the influence
      of the five factors on the inulinase production by strain G7a. Then, five levels
      of the five factors above were further optimized using the CCD. Finally, the
      optimal parameters obtained with the RSM were the initial moisture 61.5%,
      inoculum 2.75%, the amount ratio of wheat bran to rice husk 0.42, temperature 29
      degrees C, pH 5.5. Under the optimized conditions, 420.9 U g(-1) of dry substrate
      of inulinase activity was reached in the solid-state fermentation culture of
      strain G7a within 120 h whereas the predicted maximum inulinase activity of 436.2
      U g(-1) of inulinase activity of 436.2 U g(-1) of dry weight was derived from the
      RSM regression. This is the highest inulinase activity produced by the yeast
      strain reported so far. A large amount of monosaccharides and oligosaccharides
      were detected after inulin hydrolysis by the crude inulinase.

PMID- 18726620
TI  - The R229Q mutation in NPHS2 may predispose to proteinuria in thin-basement
      membrane nephropathy.
AB  - Thin-basement-membrane nephropathy (TBMN) is characterized by persistent
      dysmorphic hematuria, and the presence of proteinuria is a risk factor for renal
      impairment. TBMN is often due to mutations in the COL4A3 and COL4A4 genes, and
      this study determined whether additional mutations in genes encoding other
      structures in the glomerular filtration barrier contributed to the development of
      proteinuria. Fifty-six unrelated individuals with TBMN including 18 (32%) with
      proteinuria > or = 300 mg/L and ten (18%) with proteinuria > or = 500 mg/L were
      studied. Deoxyribonucleic acid (DNA) was screened for NPHS2 mutations and
      variants (R138Q and P375L) using single-stranded conformational analysis (SSCA)
      and for the R229Q mutation by sequencing. DNA was also screened for ACTN4
      mutations. R229Q was more common in patients with TBMN and proteinuria > or = 500
      mg/L (p < 0.05), and a possible NPHS2 mutation (671G>A, R224H) was identified in
      one patient with proteinuria 700 mg/L. No other NPHS2 variants correlated with
      proteinuria, and no ACTN4 mutations were found. Individuals with TBMN and R229Q
      are carriers of the autosomal recessive forms of both Alport syndrome and
      familial focal segmental glomerulosclerosis (FSGS). The early demonstration of
      R229Q in individuals with TBMN may indicate those at increased risk of
      proteinuria and renal impairment.

PMID- 18726621
TI  - Cloning, extracellular expression and characterization of a predominant beta
      CGTase from Bacillus sp. G1 in E. coli.
AB  - The cyclodextrin glucanotransferase (CGTase, EC 2.4.1.19) gene from Bacillus sp.
      G1 was successfully isolated and cloned into Escherichia coli. Analysis of the
      nucleotide sequence revealed the presence of an open reading frame of 2,109 bp
      and encoded a 674 amino acid protein. Purified CGTase exhibited a molecular
      weight of 75 kDa and had optimum activity at pH 6 and 60 degrees C. Heterologous
      recombinant protein expression in E. coli is commonly problematic causing
      intracellular localization and formation of inactive inclusion bodies. This paper
      shows that the majority of CGTase was secreted into the medium due to the signal
      peptide of Bacillus sp. G1 that also works well in E. coli, leading to easier
      purification steps. When reacted with starch, CGTase G1 produced 90% beta
      cyclodextrin (CD) and 10% gamma-CD. This enzyme also preferred the economical
      tapioca starch as a substrate, based on kinetics studies. Therefore, CGTase G1
      could potentially serve as an industrial enzyme for the production of beta-CD.

PMID- 18726622
TI  - Development of a biochip using antibody-coated gold nanoparticles to detect
      specific bioparticles.
AB  - This study developed a method of detecting bioparticles such as Salmonella that
      exist in the biological samples. The method employed a substrate with interlaced
      comb-like electrodes into which the mixtures of biological samples and antibody
      coated gold nanoparticles were added. The alternative signals with appropriate
      frequency bands were then conducted into the comb-like electrodes to change the
      dielectrophoresis force. The gold-modified Salmonella can be adsorbed on the
      edges of the electrodes and isolated from various biological samples. The
      impedance of the adsorbed Salmonella on the edges of the electrodes was measured
      and comparison of the impedance between the electrodes with and without
      Salmonella can quantify the amount of the adsorbed Salmonella.

PMID- 18726623
TI  - Treatment of mixed domestic-industrial wastewater using cyanobacteria.
AB  - Alexandria Sanitary Drainage Company (ASDCO), Alexandria, Egypt has two primary
      treatment plants, the eastern and the western wastewater treatment plants (EWTP
      and WWTP) that receive mixed domestic-industrial influents and discharge into L.
      Mariut. The lake is subjected therefore to severe levels of pollution and
      dominated by members of cyanobacteria that can cope with the high pollution load
      in the lake water. Isolation and utilization of the locally generated
      cyanobacterial biomass for remediation processes of highly toxic pollutants
      offers a very efficient and cheap tool for governmental or private industrial
      activities in Alexandria and will generate a source of revenue in Egyptian
      localities. The main objective of the present study was to investigate the
      biodegradation and biosorption capacity of some potential cyanobacterial species
      dominating the lake ecosystem toward organic and inorganic contaminants polluting
      the primary-treated effluents of the EWTP and WWTP. The primary effluents were
      subjected to biological treatment using three axenic cyanobacterial strains
      (Anabaena oryzae, Anabaena variabilis and Tolypothrix ceytonica) as batch system
      for 7 days. Removal efficiencies (RE) of the different contaminants were
      evaluated and compared. Results confirmed the high efficiencies of the
      investigated species for the removal of the target contaminants which were
      species and contaminant-dependent. BOD5 and COD recorded 89.29 and 73.68% as
      maximum RE(s) achieved by Anabaena variabilis and Anabaena oryzae, respectively.
      The highest RE of the TSS recorded 64.37% achieved by Tolypothrix ceytonica,
      while 38.84% was recorded as the highest TSD RE achieved by Anabaena variabilis.
      Tolypothrix ceytonica also exhibited the highest RE for FOG recorded 93.75%.
      Concerning the contaminant metals, Tolypothrix ceytonica showed the highest
      biosorption capacity where 86.12 and 94.63% RE were achieved for Zn and Cu,
      respectively. In conclusion, results of the present study confirmed the
      advantageous potential of using the tested cyanobacterial species for the
      treatment of contaminated wastewater. Results also clearly showed the quality
      improvement of the discharged wastewater which in turn will eliminate or at least
      minimize the expected deterioration of the receiving environment.

PMID- 18726624
TI  - INDISIM-YEAST: an individual-based simulator on a website for experimenting and
      investigating diverse dynamics of yeast populations in liquid media.
AB  - Simulation modelling can be used to capture and mimic real-world microbial
      systems that, unlike the real-world, can then be experimented upon as a new kind
      of experimental milieu. Individual-based models, in which individuals interact
      dynamically with each other as structural elements in the model world, exemplify
      this view of simulation modelling. These models are more difficult to analyze,
      understand and communicate than traditional analytical models. It is good
      practice to provide executable versions that perform simulation results. INDISIM
      YEAST, developed to deal with yeast populations in liquid media, models the
      evolution of a set of yeasts by setting up rules of behavior for each individual
      cell according to its own biological regulations and characteristics. The aim of
      this work is to develop and present a website from which INDISIM-YEAST is
      accessible, and how to carry out yeast simulations to further the skills
      associated with the use of this individual-based simulator. A good and useful way
      to analyze this yeast simulator is to experiment and explore the manner in which
      it reacts to changes in parameter values, initial conditions or assumptions. The
      application results in a very versatile program that could be used in controlled
      simulation experiments via the Internet.

PMID- 18726625
TI  - Quantitative contributions of bacteria and of Deinococcus geothermalis to
      deposits and slimes in paper industry.
AB  - Deinococcus geothermalis has frequently been isolated from pink colored deposits
      of paper industry processes. Laboratory studies have shown that D. geothermalis
      is capable of forming on nonliving surfaces patchy biofilms that are resistant to
      adverse agents such as extreme pH, desiccation, solubilising detergents and
      biocides. This study was done to quantitatively assess the role of D.
      geothermalis as a biofouler in paper industry. Colored deposits were collected
      from 24 European and North American paper and board machines and the densities of
      the bacterial 16S rRNA genes and those of the red slime producers D. geothermalis
      and Meiothermus spp. were measured by QPCR (quantitative real time PCR). D.
      geothermalis was found at nine machines, usually from splash area deposits, but
      its contribution was minor, 0.001-1%, to the total bacterial burden of 8.3 to log
      10.5 log units per gram wet-weight of the deposits. When D. geothermalis was
      found in a measurable quantity, Meiothermus spp. also was found, often in bulk
      quantity (7-100% of the total bacteria). The data are in line with the properties
      of D. geothermalis known from laboratory biofilm studies, indicating this species
      is a pioneer coloniser of machine surfaces and may help other bacteria to adhere
      and grown into biofilms, rather than competing with them.

PMID- 18726627
TI  - The verbalization of multiple strategies in a variant of the traveling
      salesperson problem.
AB  - What kinds of strategies do humans employ when confronted with a complex spatial
      task, and how do they verbalize these strategies? Previous research concerned
      with the well-known traveling salesperson problem (TSP) typically aimed at the
      identification of a generally applicable heuristics that adequately represents
      human behavior in relation to the abstract task of combining points. This paper
      adopts a novel perspective in two respects. On the one hand, it addresses the
      strategies people employ when confronted with a more complex task, involving
      distractors and feature information rather than identical points. On the other
      hand, retrospective linguistic representations of the strategies used are
      analyzed in relation to the behavioral data, using discourse analytic methods.
      Results show that both the behavioral results and the verbalizations point to a
      range of strategies related to those proposed for solving abstract TSPs. However,
      in contrast to earlier accounts in the literature, the participants employ a
      repertory of multi-faceted strategies and planning processes, simplifying and
      structuring the problem space across subtasks and processes in flexible ways.
      These findings provide further insight into the nature of human strategies in
      spatial problem solving tasks and their retrospective verbalization, highlighting
      how procedures generally known in the literature may be adapted to more complex
      tasks, and how they may be verbalized spontaneously.

PMID- 18726626
TI  - 1H MR spectroscopy as a diagnostic tool for cerebral creatine deficiency.
AB  - OBJECTIVE: Total creatine (tCr) constitutes one of the most prominent signals in
      human brain MR spectra. A significant decrease in the tCr signal indicates a
      severe disorder of creatine metabolism. We describe the potential of 1H MR
      spectroscopy in differential diagnosis of creatine transporter (SLC6A8)
      deficiency syndrome. MATERIALS AND METHODS: Two siblings, a 7-year-old female
      presenting with mild psychomotor delay, and a 5-year-old male with severe
      psychomotor retardation, epilepsy and autistic spectrum of problems including
      speech delay, underwent MR examination because of suspected creatine deficiency.
      After the MRI examination, 1H MR spectroscopy using the CSI technique was
      performed. RESULTS: Metabolic images of N-acetylaspartate, tCr and choline
      concentrations showed a very low tCr signal in the male, which was approximately
      three times lower than in his sister (male/female/controls: tCr=1.6/4.6/7.5 mM).
      Despite creatine supplementation, no improvement in clinical status and tCr
      concentration in the MR spectra of the male was observed and diagnosis of SLC6A8
      deficiency was proposed. Sequence analysis of the SLC6A8 gene revealed a novel
      pathogenic frameshift mutation c.219delC; p.Asn74ThrfsX23, hemizygous in the male
      and heterozygous in the female. CONCLUSIONS: The diagnosis of X-linked mental
      retardation caused by the SLC6A8 deficiency can be independently established by
      1H MR spectroscopy.

PMID- 18726628
TI  - Numerical flow simulation in the post-endoscopic sinus surgery nasal cavity.
AB  - In this study we utilized computational fluid dynamic (CFD) techniques to
      construct a numerical simulation of nasal cavity airflow pre and post virtual
      functional endoscopic surgery (FESS). A healthy subject was selected, and CFD
      techniques were then applied to construct an anatomically and proportionally
      accurate three-dimensional nasal model based on nasal CT scans. A virtual FESS
      intervention was performed numerically on the normal nasal model using Fluent
      software. Navier-Stokes and continuity equations were used to calculate and
      compare airflow, velocity, distribution and pressure in both the pre and post
      FESS models. In the post-FESS model, there was an increase in airflow
      distribution in the maxillary, ethmoid and sphenoid sinuses, and a 13% increase
      through the area connecting the middle meatus and the surgically opened ethmoid.
      There was a gradual decrease in nasal resistance in the posterior ethmoid sinus
      region following FESS. These findings highlight the potential of this technique
      as a powerful preoperative assessment tool to aid clinical decision-making.

PMID- 18726629
TI  - Spatial synchronization of an insole pressure distribution system with a 3D
      motion analysis system for center of pressure measurements.
AB  - Insole pressure systems are often more appropriate than force platforms for
      analysing center of pressure (CoP) as they are more flexible in use and indicate
      the position of the CoP that characterizes the contact foot/shoe during gait with
      shoes. However, these systems are typically not synchronized with 3D motion
      analysis systems. The present paper proposes a direct method that does not
      require a force platform for synchronizing an insole pressure system with a 3D
      motion analysis system. The distance separating 24 different CoPs measured
      optically and their equivalents measured by the insoles and transformed in the
      global coordinate system did not exceed 2 mm, confirming the suitability of the
      method proposed. Additionally, during static single limb stance, distances
      smaller than 7 mm and correlations higher than 0.94 were found between CoP
      trajectories measured with insoles and force platforms. Similar measurements were
      performed during gait to illustrate the characteristics of the CoP measured with
      each system. The distance separating the two CoPs was below 19 mm and the
      coefficient of correlation above 0.86. The proposed method offers the possibility
      to conduct new experiments, such as the investigation of proprioception in
      climbing stairs or in the presence of obstacles.

PMID- 18726630
TI  - Biomechanical analysis of structural deformation in living cells.
AB  - Most tissues are subject to some form of physiological mechanical loading which
      results in deformation of the cells triggering intracellular mechanotransduction
      pathways. This response to loading is generally essential for the health of the
      tissue, although more pronounced deformation may result in cell and tissue
      damage. In order to determine the biological response of cells to loading it is
      necessary to understand how cells and intracellular structures deform. This paper
      reviews the various loading systems that have been adopted for studying cell
      deformation both in situ within tissue explants and in isolated cell culture
      systems. In particular it describes loading systems which facilitate
      visualisation and subsequent quantification of cell deformation. The review also
      describes the associated microscopy and image analysis techniques. The review
      focuses on deformation of chondrocytes with additional information on a variety
      of other cell types including neurons, red blood cells, epithelial cells and skin
      and muscle cells.

PMID- 18726631
TI  - Patient-specific computational fluid dynamic simulation of a bilateral
      bidirectional Glenn connection.
AB  - Computational fluid dynamics (CFD) have been used to investigate the hemodynamic
      performance in cavopulmonary anastomosis and resulted in improved operative
      design. In this study, CFD simulations were performed in a patient-specific
      bilateral bidirectional Glenn (BBDG) connection model and the power losses as
      well as flow features at different levels of predetermined pulmonary flow splits
      were calculated and compared. The control volume power loss varied between 0.64
      and 1.02 mW when the flow ratio of left pulmonary artery/right pulmonary artery
      changed from 80:20 to 20:80. The flow patterns within the connection area and the
      static pressures in the four vessels differed from each other as the pulmonary
      flow split changed. Power loss and flow patterns of this BBDG connection were
      influenced by the pulmonary flow split.

PMID- 18726636
TI  - ESNR 2008. Abstracts of the 33rd European Society of Neuroradiology Annual
      Meeting, 17th Advanced Course and 1st Interventional Advanced Course, September
      18-21, 2008, Cracow, Poland.

PMID- 18726632
TI  - Regulation of steroid hormone biosynthesis by the cytoskeleton.
AB  - Steroid hormones are synthesized in response to signaling cascades initiated by
      the trophic peptide hormones derived from the anterior pituitary. The mechanisms
      by which these peptide hormones regulate steroid hormone production are
      multifaceted and include controlling the transcription of steroidogenic genes,
      regulating cholesterol (substrate) uptake and transport, modulating steroidogenic
      enzyme activity, and controlling electron availability. Cytoskeletal polymers
      such as microfilaments and microtubules have also been implicated in regulating
      steroidogenesis. Of note, steroidogenesis is a multi-step process that occurs in
      two organelles, the endoplasmic reticulum (ER) and the mitochondrion. However,
      the precise mechanism by which substrates are delivered back and forth between
      these two organelles is unknown. In this review we will discuss the role of
      components of the cytoskeleton in conferring optimal steroidogenic potential.
      Finally, we present data that identifying a novel mechanism by which sphingosine
      1-phosphate induces mitochondrial trafficking to promote steroidogenesis.

PMID- 18726641
TI  - [Diagnostic heart catheterization].

PMID- 18726642
TI  - [Percutaneous coronary interventions (PCI)].

PMID- 18726643
TI  - [Drug-eluting coronary stents and drug eluting balloon catheters: summary of the
      position papers of the DGK].

PMID- 18726644
TI  - Effect of open heart surgery with cardiopulmonary bypass on peripheral blood
      lymphocyte apoptosis in children.
AB  - Children undergoing cardiopulmonary bypass (CPB) operations have an increased
      risk for the development of immunosuppression and severe infection. Lymphocyte
      apoptosis plays an important role in regulating immune responses. This study
      aimed to investigate the effect of open heart surgery with CPB on peripheral
      blood lymphocyte (PBL) apoptosis and the possible mechanism of lymphocyte
      apoptosis in infants and young children. This study enrolled 20 consecutive
      infants and children as a CPB group and 20 age-matched children who underwent
      patent arterial duct closure without CPB as control subjects. Samples were taken
      from peripheral blood after induction of anesthesia (preoperatively) and again 24
      h after the operations. The degree of apoptosis and the expression level of Fas
      (CD95) on PBL were measured using flow cytometry. The percentage of lymphocyte
      apoptosis significantly increased after surgery in both groups, but it was much
      higher in the children with CPB than in those without CPB (14.46%+/-4.83% vs.
      7.33%+/-1.43%; p<0.01). The expression level of Fas in the individuals with CPB
      was significantly higher than in those without CPB (52.80%+/-8.80% vs. 37.82%+/
      6.32%; p<0.01). As shown by the study findings, both surgical stress and CPB can
      induce PBL apoptosis, which may lead to lymphopenia after open heart surgery with
      CPB for infants and young children.

PMID- 18726645
TI  - Interventions complementing surgery as part of multistage treatment for
      hypoplastic left heart syndrome: one center's experience.
AB  - BACKGROUND: Interventional procedures often are used as part of multistage
      treatment for hypoplastic left heart syndrome (HLHS). This study aimed to
      evaluate the efficacy of interventions in multistage treatment of HLHS. METHODS
      AND RESULTS: Between 1999 and 2007, 78 interventions were performed for 58
      children with HLHS at different stages of surgical treatment. Group 1, involving
      30 interventions for 22 patients with postoperative pulmonary arterial stenosis,
      showed reduced pulmonary artery pressure and increased vessel diameter. Group 2,
      involving 15 interventions after the Norwood operation for 12 patients with
      aortic arch obstruction, showed success for 11 patients. Group 3, involving eight
      balloon angioplasties of narrowed Glenn anastomosis for seven patients, showed
      abolition of the pressure gradient between the superior vena cava and the right
      pulmonary artery. Group 4, involving eight interventional closures of a
      fenestration for eight patients after a Fontan operation, showed increased oxygen
      saturation for all eight patients. Group 5, involving seven interventions for six
      patients in whom venovenous collaterals were closed percutaneously, showed
      improved oxygen saturation. For Group 6, uncommon miscellaneous interventions
      were used to stabilize the patients' condition before the next surgical
      treatment. CONCLUSIONS: Interventional procedures play an important role during
      multistage treatment of HLHS. They allow for a reduction in the number of
      operations or stabilization of the patients' condition before the next surgical
      treatment.

PMID- 18726646
TI  - CT colonography: same-day tagging regimen with iodixanol and reduced cathartic
      preparation.
AB  - The purpose of the study was to test the tagging performance and patient's
      acceptance of a reduced cathartic preparation, based on iodixanol and PEG,
      administered to patients 3 h before the exam. One hundred and thirty-two
      asymptomatic patients were enrolled. As colonic cleansing we used PEG macrogol
      3350. For fluid tagging iodixanol was orally administered 3 h before the exam, in
      a total dose of 50 mL mixed with 34.8 g of PEG in 750 mL of water. Image's review
      showed 446 segments (56.4%) clean of feces and 346 segments (43.6%) with feces.
      Untagged fluid was observed in 74/706 (10.5%) segments; inhomogeneous tagging in
      129/706 (16%); the average density of fluid was 1054.74 UH in the cecum-ascending
      colon and 905.14 UH in the descending-sigmoid colon; the average difference of
      density between right and left colonic segments was 149 UH, and it was
      statistically significant (P = 0.016). No side effects related to the consumption
      of Movicol were reported. Very few side effects related to the tagging solution
      were reported: mild nausea in 7 (0.05%) patients, mild diarrhea in 10 (0.07%). An
      average rank of 9 points (SD +/- 1) on a 10-point scale (10 = no discomfort, 0 =
      severe discomfort) resulted from the self-administered questionnaire, showing an
      excellent acceptance of the preparation. Same day fluid tagging with iodixanol
      provides an optimal fluid tagging, it is completely tolerated by the patient, and
      it can be performed under medical control.

PMID- 18726648
TI  - A brief history of Orlo H. Clark.

PMID- 18726647
TI  - The accuracy of sentinel lymph node biopsy in the treatment of multicentric
      invasive breast cancer using a subareolar injection of tracer.
AB  - BACKGROUND: The aim of this study was to evaluate the feasibility and the
      accuracy of sentinel lymph node biopsy in multicentric breast cancer (MBC)
      performed by means of a subareolar (SA) injection of both 99Tc-labeled human
      albumin colloid and lymphazurin. METHODS: Between January 2002 and October 2007,
      34 patients with MBC with clinically negative axilla underwent sentinel lymph
      node biopsy (SLNB) followed by total axillary node dissection (AD). Overall
      successful identification rate of SLN was 100%; there were no false negatives and
      overall accuracy rate was 100%. RESULTS: The mean number of sentinel lymph nodes
      (SLNs) identified was 1.8 +/- 0.88 (range = 1-4); the mean number of axillary
      lymph nodes examined was 21.4 +/- 5.76 (range = 8-36). CONCLUSIONS: The authors
      conclude that SA injection of the tracer is feasible and efficacious in the
      identification of the SLN. The accuracy of SLNB in MBC is comparable to that
      obtained in unifocal disease.

PMID- 18726650
TI  - Topical sucralfate post-hemorrhoidectomy: an affordable and feasible treatment
      option.

PMID- 18726651
TI  - Prediction of lymph node status in superficial esophageal carcinoma.
AB  - BACKGROUND: Esophageal carcinoma is among the cancers with the worst prognosis.
      Real chances for cure depend on both early recognition and early treatment. The
      ability to predict lymph node involvement allows early curative treatment with
      less invasive approaches. AIMS: To determine clinicohistopathological criteria
      correlated with lymph node involvement in patients with early esophageal cancer
      (T1) and to identify the best candidate patients for local endoscopic or less
      invasive surgical treatments. METHODS: A total of 98 patients with pT1 esophageal
      cancer [67 with squamous cell carcinomas (SCC) and 31 with adenocarcinomas (ADK)]
      underwent Ivor-Lewis or McKeown esophagectomy in the period between 1980 and 2006
      at our institution. Based on the depth of invasion, lesions were classified as
      m1, m2, or m3 if mucosal, and sm1, sm2, or sm3 if submucosal. RESULTS: The rates
      of lymph node metastasis were 0% for the 27 mucosal carcinomas (T1m) and 28% for
      the 71 submucosal (T1sm) carcinomas (P < 0.001). Sm1 carcinomas were associated
      with a lower rate of lymph-node metastasis (8.3% versus 49 % sm2/3, P = 0.003).
      As for histotype, the rates of lymph node metastasis for sm1 were 0% for ADK and
      12.5% for SCC; for sm2/3 there were no significant differences. On multivariate
      analysis, depth of infiltration, lymphocytic infiltrate, angiolymphatic and
      neural invasion were significantly associated with lymph node involvement. Neural
      invasion was the single parameter with the greatest accuracy (82%); depth of
      infiltration and angiolymphatic invasion had 75% accuracy. Altogether these three
      parameters had an accuracy of 97%. Five-year survival rate was 56.7% overall:
      77.7% for T1m and 53.3% for T1sm (P = 0.048). CONCLUSIONS: The most important
      factors for predicting lymph node metastasis in early esophageal cancer are depth
      of tumor infiltration, angiolymphatic invasion, neural invasion and grade of
      lymphocytic infiltration. The best candidates for endoscopic therapy are tumors
      with high-grade lymphocytic infiltration, no angiolymphatic or neural invasion,
      mucosal infiltration or sm1 (only for ADK), and tumor <1 cm in size. For sm SCC
      and sm2/3 ADK the treatment of choice remains esophagectomy with standard
      lymphadenectomy.

PMID- 18726652
TI  - The keystone island and pedicle flap: a handy local flap for soft tissue
      reconstruction.

PMID- 18726653
TI  - Increased tissue diffusion of oxaliplatin during laparoscopically assisted versus
      open heated intraoperative intraperitoneal chemotherapy (HIPEC).

PMID- 18726654
TI  - Myths and legends in orthopaedic practice: are we all guilty?
AB  - Over years of practice, many beliefs and practices become entrenched as tried and
      tested, and we subconsciously believe they are based on scientific evidence. We
      identified nine such beliefs by interviewing orthopaedic surgeons in which
      studies (or lack thereof) apparently do not support such practices. These are:
      changing the scalpel blade after the skin incision to limit contamination;
      bending the patient's knee when applying a thigh tourniquet; bed rest for
      treatment of deep vein thrombosis; antibiotics in irrigation solution; routine
      use of hip precautions; routine use of antibiotics for the duration of wound
      drains; routine removal of hardware in children; correlation between operative
      time and infection; and not changing dressings on the floor before scrubbing. A
      survey of 186 practicing orthopaedic surgeons in academic and community settings
      was performed to assess their routine practice patterns. We present the results
      of the survey along with an in-depth literature review of these topics. Most
      surgeon practices are based on a combination of knowledge gained during training,
      reading the literature, and personal experience. The results of this survey
      hopefully will raise the awareness of the selected literature for common
      practices.

PMID- 18726655
TI  - Reliability and validity of the cross-culturally adapted German Oxford hip score.
AB  - There is currently no German version of the Oxford hip score. Therefore we sought
      to cross-culturally adapt and validate the Oxford hip score for use with German
      speaking patients (OHS-D) with osteoarthritis of the hip using a forward-backward
      translation procedure. We then assessed the new score in 105 consecutive patients
      (mean age, 63.4 years; 48 women) undergoing THA. We specifically determined: the
      number of fully completed questionnaires, reliability, concurrent validity by
      correlation with the WOMAC, Harris hip score, and SF-12, and distribution of
      floor and ceiling effects. We received 96.6% fully completed questionnaires. An
      intraclass correlation coefficient of 0.90 and Cronbach's alpha of 0.87 suggested
      the OHS-D was reliable. Correlation coefficients between the OHS-D and the WOMAC
      total score, pain subscale, stiffness subscale, and physical function subscale
      were 0.82, 0.70, 0.68, and 0.82, respectively. OHS-D correlated with the Harris
      hip score (r = 0.63) and the physical component scale of the SF-12 (r = 0.58). We
      observed no ceiling or floor effects. The OHS-D appeared a reliable and valid
      measurement tool for assessing pain and disability with German-speaking patients
      with hip osteoarthritis. LEVEL OF EVIDENCE: Level I, diagnostic study. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 18726656
TI  - Effect of gender and preoperative diagnosis on results of revision total knee
      arthroplasty.
AB  - Recent studies question an effect of gender on outcome of primary TKA. We
      questioned whether the results of revision TKA were affected by gender. We
      separated 67 revision TKAs by gender and preoperative diagnosis into four groups
      (arthrofibrosis, infection, instability, and wear and loosening). Each revision
      TKA was individually matched by age and gender to two primary TKAs. Postoperative
      Knee Society pain and function scores after revision TKA were lower than for
      primary TKA for both females and males. However, postoperative Knee Society pain
      and function scores were similar in males and females. Postoperative pain and
      function scores were lower for all revision groups compared with primary TKA,
      except for pain and function scores after revision for instability. Postoperative
      pain and function scores were higher for instability and wear or loosening than
      for arthrofibrosis. Our data suggest the results of revision TKA are affected by
      preoperative diagnosis but not gender. LEVEL OF EVIDENCE: Level III,
      retrospective matched cohort study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 18726657
TI  - To resurface or not to resurface the patella in total knee arthroplasty.
AB  - The management of the patellar articular surface at the time of primary total
      knee arthroplasty (TKA) is controversial. We used expected-value decision
      analysis to determine whether the patella should be resurfaced in TKA, and also
      whether secondary resurfacing on an unresurfaced patella is worthwhile. Outcome
      probabilities and utility values were derived from randomized controlled trials
      only. A decision tree was constructed and fold-back analysis was performed to
      ascertain the best treatment path. Sensitivity analyses were performed to
      determine the effect on decision-making of varying outcome probabilities and
      utilities. Our model showed patellar resurfacing is the best management strategy
      for the patella at the time of primary TKA. This decision is robust to changes in
      the specific data: the best path would remain the same as long as the incidence
      of persistent anterior knee pain (AKP) with resurfacing remains less than 29%
      (current mean, 12%) or the incidence of AKP after nonresurfacing falls below 12%
      (current mean, 26%). Delayed (ie, secondary) patellar resurfacing for ongoing
      patellar pain provides inferior results for the majority of patients. LEVEL OF
      EVIDENCE: Level II, decision analysis. See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 18726658
TI  - ABJS/C.T. Brighton Workshop on Musculoskeletal Trauma in Developing Countries:
      editorial comment.

PMID- 18726659
TI  - Time series analysis of treatment adherence patterns in individuals with
      obstructive sleep apnea.
AB  - BACKGROUND: Adherence to medical recommendations is often suboptimal, making
      examination of adherence data an important scientific concern. Studies that
      attempt to predict or modify adherence often face the problem that adherence as a
      dependent variable is complex and non-normally distributed. Traditional
      statistical approaches to adherence data may mask individual variability that may
      guide clinician and researcher's development of adherence interventions. In this
      study, we employ time series analysis to examine adherence patterns objectively
      in patients with obstructive sleep apnea (OSA). Although treatment adherence is
      poor in OSA, state-of-the-art adherence monitoring allows a comprehensive
      examination of objective data. PURPOSE: The purpose of the study is to determine
      the number and types of adherence patterns seen in a sample of patients with OSA
      receiving positive airway pressure (PAP). METHODS: Seventy-one moderate to severe
      OSA participants with 365 days of treatment data were studied. RESULTS: Adherence
      patterns could be classified into seven categories: (1) Good Users (24%), (2)
      Slow Improvers (13%), (3) Slow Decliners (14%), (4) Variable Users (17%), (5)
      Occasional Attempters (8%), (6) Early Drop-outs (13%), and (7) Non-Users (11%).
      CONCLUSIONS: Time series analysis provides a useful method for examining
      adherence while maintaining a focus on individual differences. Implications for
      future research are discussed.

PMID- 18726662
TI  - [Stress hyperglycemia--effect on morbidity and mortality in acute patients].

PMID- 18726665
TI  - Endovascular repair of a dissecting thoracic aortic aneurysm with contained
      rupture of the false lumen.

PMID- 18726663
TI  - [Pathophysiology and therapy of benign prostatic hyperplasia].
AB  - Benign prostatic hyperplasia (BPH) and benign prostatic enlargement (BPE) are
      among the most frequent medical disorders of elderly men and cause a number of
      annoying symptoms of the lower urinary tract (LUTS), leading to reduced quality
      of life and severe complications, including acute urinary retention. Nodular
      overgrowth of the epithelium and in particular the fibromuscular tissue is
      observed in the transition zone and periurethral areas. In particular, functional
      and phenotypic transdifferentiation of fibroblasts into myofibroblasts is a
      hallmark of the tissue remodeling in the benign hyperplastic prostate. BPH/BPE
      have a complex pathophysiology with a multitude of endocrine and local factors
      involved. Two risk factors, namely aging and circulating androgens, contribute
      significantly to risk of BPH/BPE. One of the primary initiating mechanisms
      appears to be a consequence of age-related changes in systemic sex steroid
      hormone levels accompanied by alterations in local androgen metabolism. This
      results in the disruption of the delicate balance of interacting growth factor
      signaling pathways and stromal/epithelial interactions generating a growth
      promoting and tissue remodeling microenvironment that leads to an increase in
      prostate volume. Secondarily, altered cytokine and chemoattractant production by
      the remodeled stroma promotes local inflammation that may further contribute to
      disease progression via lymphocyte-derived inflammatory cytokines and reactive
      oxygen/nitrogen species. Local hypoxia as a result of increased oxygen demands of
      proliferating cells may induce low levels of reactive oxygen species promoting
      neovascularization and fibroblast-to-myofibroblast transdifferentiation. Medical
      therapies for LUTS due to BPH/BPE have changed little over the past 15 years with
      mainstay treatments being alpha-adrenoreceptor blockade and 5alpha-reductase
      inhibitors. We provide an in depth view of the mechanisms underlying BPH/BPE and
      relate new research findings to the clinical picture with the prospect of novel
      therapeutic targets, including selective hormone antagonists/agonists, anti
      stromal therapy, vitamin-D analogues and approaches to redress the redox
      imbalance.

PMID- 18726664
TI  - The involvement of mycotoxins in the development of endemic nephropathy.
AB  - Endemic nephropathy is a human kidney disease that still escapes scientific
      explanation. It is accompanied by a high incidence of urothelial tumors in rural
      populations in endemic areas, which suggests that a natural nephrotoxic and
      carcinogenic compound may be involved in the etiology. The most imputed causative
      agent of endemic nephropathy is the mycotoxin ochratoxin A (OTA), because of its
      confirmed nephrotoxic and carcinogenic action. This paper presents a review of
      studies of OTA in food collected in the endemic areas and in blood and urine of
      their residents. Data on the co-occurrence of OTA and other nephrotoxic and
      carcinogenic mycotoxins such as citrinin and fumonisin B(1) in food are also
      presented. Unfortunately, there is no study on the co-occurrence of OTA and other
      mycotoxins in humans and there is only one study on fumonisin B(1) exposure in
      endemic areas. The paper also presents experimental data on cultured cells and
      laboratory animals treated with combinations of OTA and other nephrotoxic
      mycotoxins, because most such combinations show a synergistic effect. The
      occurrence of OTA- and aristolochic acid-DNA adducts is also presented.

PMID- 18726666
TI  - Association of stress hyperglycemia and atrial fibrillation in myocardial
      infarction.
AB  - BACKGROUND: Stress hyperglycemia has an untoward effect on prognosis in acute
      myocardial infarction (AMI). Evidence on the interrelationship between stress
      hyperglycemia and atrial fibrillation (AF) in AMI is sparse. We hypothesized that
      stress hyperglycemia and AF, both being markers of worse in-hospital prognosis,
      may be interrelated and we therefore analyzed the relationship between stress
      hyperglycemia and AF in AMI. PATIENTS AND METHODS: The study was a retrospective
      analysis of 543 patients with AMI. The average age was 63.8 +/- 10.6 years and
      54.9% were male. RESULTS: AF was more prevalent in 200 AMI patients with
      admission glucose >or= 8.0 mmol/l (15.00%) than in 343 patients with admission
      glucose < 8 mmol/l (7.87%), Pearson's chi-squared P = 0.010, OR 2.07 (95% CI
      1.180-3.637). In AMI patients with neither stress hyperglycemia nor AF, in
      hospital mortality was 1.67%; in patients with stress hyperglycemia without AF,
      the mortality was 3.85%. In patients with AF without stress hyperglycemia,
      mortality was high at 13.04%, and in patients with both stress hyperglycemia and
      AF it was extremely high at 24.14%. Hyperglycemia (r = 0.1680, P = 0.0472) but
      not AF correlated with the size of the AMI. Compared with an AF prevalence of
      8.28% in the normoglycemic group, AF was found more often (14.65%) in a group
      with diabetes mellitus (DM), Pearson's chi-squared P = 0.02, OR = 2.04 (95% CI
      1.06-3.93). There was no significant difference in the occurrence of AF between
      patients with previously diagnosed DM and those with new-onset DM (Fisher's exact
      test P = 0.34). CONCLUSIONS: Stress hyperglycemia is associated with increased
      prevalence of AF in AMI. Patients with both stress hyperglycemia at admission
      (>or= 8.0 mmol/l) and AF had almost 14.5 times higher in-hospital mortality than
      patients who had neither stress hyperglycemia nor AF. Stress hyperglycemia was an
      independent predictor of the in-hospital mortality in multivariate regression
      analysis, but AF was not.

PMID- 18726667
TI  - Comparing stress levels in children aged 2-8 years and in their accompanying
      parents during first-time versus repeated voiding cystourethrograms.
AB  - OBJECTIVES: Invasive procedures such as voiding cystourethrograms (VCUGs) cause
      distress in both children and their accompanying parents. The main purpose of
      this study was to examine whether stress levels in children and their parents
      differ during first-time and repeated VCUGs. The second objective was to examine
      the relationship between parental behavior (behavior promoting child coping and
      behavior promoting child distress), parental stress levels and child distress in
      first-time versus repeated VCUGs. METHODS: In a prospective study, the distress
      behavior of 31 children aged 2-8 years who were undergoing a repeated VCUG was
      examined. A second group of 31 children who were undergoing a VCUG for the first
      time served as a control sample. Child and parental behavior during the VCUG was
      coded by three independent observers using a standardized rating scale (CAMPIS-R,
      Blount et al.). Children reported on their stress levels using a faces scale;
      parents and radiologists rated the child's distress on a visual analog scale.
      Similarly, parents assessed their own stress levels on a visual analog scale.
      RESULTS: The stress levels of children undergoing a repeated VCUG do not differ
      from those of children undergoing a VCUG for the first time, but parental stress
      levels were significantly lower during repeated VCUGs. In both VCUG groups there
      was significant positive correlation between parental distress-promoting behavior
      and child distress, and between parental stress levels and child distress.
      Parental coping-promoting behavior showed no significant correlation with child
      distress or parental stress levels in either VCUG group. Parental stress levels
      and parental distress-promoting behavior correlated positively only for repeated
      VCUGs. Neither parental coping- nor distress-promoting behavior differed between
      first-time versus repeated VCUG groups. CONCLUSIONS: Repeated VCUGs and first
      time VCUGs are both highly distressing procedures for children. Even though
      parental stress levels are lower during repeated VCUGs, spontaneous parental
      behavior proves to be ineffective or even counterproductive in reducing the
      child's distress. Further research into efficient counseling and training methods
      for parents and children undergoing VCUGs is required.

PMID- 18726668
TI  - High seroprevalence of varicella, measles, mumps, rubella and pertussis
      antibodies in first-grade medical students.
AB  - OBJECTIVE: The aim of the study was to investigate seropositivity for five
      vaccine-preventable communicable diseases - varicella, measles, mumps, rubella
      and pertussis - in a sample of first-grade medical students. METHODS: A total of
      256 students were tested for varicella IgG antibodies. In addition, 138 of the
      students were serologically screened for measles, mumps, rubella and pertussis
      antibodies. Data on vaccination and history of measles, mumps, rubella and
      pertussis were collected. RESULTS: Immunity to varicella, measles, mumps and
      rubella was established in 97.6%, 96.4%, 97.8% and 99.3% participants,
      respectively. Anti-pertussis toxin antibodies were detected in 81.2% of the
      students. CONCLUSIONS: The rates of varicella, measles, mumps and rubella
      immunity in first-grade medical students are very high. To identify those
      students who need vaccination before commencing practical work in healthcare
      facilities, a meticulous disease and vaccination history should be taken and
      medical records should be reviewed. Medical students providing no written
      evidence of adequate vaccination status should be serologically tested and
      vaccinated if necessary.

PMID- 18726669
TI  - Serologic evidence of Anaplasma phagocytophilum infections in patients with a
      history of tick bite in central Slovakia.
AB  - The aim of this study was to determine the risks of human anaplasmosis in an area
      of central Slovakia endemic for Lyme borreliosis. The circulation of Anaplasma
      phagocytophilum in ticks and wild animals has been observed in natural foci in
      this area for several years. Samples of human sera from patients with Lyme
      borreliosis and persons with a history of recent tick bite and clinical symptoms
      indicating Lyme borreliosis were collected in central Slovakia. A total of 76
      human sera were analyzed using an indirect HGE IgG immunofluorescent assay kit.
      IgG antibodies against A. phagocytophilum were found in 19 (25%) sera (15 female,
      4 male patients). A. phagocytophilum infection was serologically confirmed in one
      (3.8%) child, 12 (38.7%) persons aged 22-56 and six (31.6%) persons older than
      56. A statistically significant difference in seroprevalence (P < 0.01) was
      observed between children (3.8%, 1/26) and adults (36%, 18/50). Antibodies
      against A. phagocytophilum were detected in seven patients with clinically
      diagnosed Lyme borreliosis and in another seven individuals with assessed
      antiborrelia antibodies. IgG antibodies against A. phagocytophilum were detected
      in five persons seronegative for borrelia. The most frequent clinical symptoms in
      patients with positive A. phagocytophilum serology were cephalalgia, arthralgia,
      myalgia, fever, exanthema, neurological symptoms and lymphadenopathy. Positive
      sera were obtained from patients living in villages and towns in the orographic
      entities Vtacnik (5/19), Stiavnicke vrchy (1/19), Kremnicke vrchy (10/19) and
      Ziarska kotlina (3/19). Our results demonstrate the risk of acquiring A.
      phagocytophilum infection in natural foci in central Slovakia. Human anaplasmosis
      should be considered in the differential diagnosis, especially in cases of acute
      febrile illness with tick-bite history.

PMID- 18726670
TI  - Transient hyperthyroidism after total parathyroidectomy for tertiary
      hyperparathyroidism: a report of two cases.
AB  - Surgical removal of enlarged parathyroid glands is the treatment of choice in
      most cases of tertiary renal hyperparathyroidism. Complications of this surgical
      procedure are rare. We report two cases of patients who developed acute
      hyperthyroidism after total parathyroidectomy with parathyroid
      autotransplantation for refractory tertiary hyperparathyroidism. The patients had
      no history or biochemical or radiologic evidence of thyroid disease. They were
      not taking drugs affecting thyroid function. Thyroid function (thyroid
      stimulating hormone, free T(3) and free T(4)) was measured preoperatively,
      immediately after surgery and again three months later. Total parathyroidectomy
      was successful in both patients. Circulating levels of parathyroid hormone were
      at the lower limit of normal values. Postoperative thyroid function tests
      demonstrated acute hyperthyroidism with a rapid increase in free T(3) and T(4)
      levels above normal and a drop in thyroid stimulating hormone below normal in
      both patients. The course of hyperthyroidism was short (normalization of fT(3)
      and fT(4) values within 14-21 days). Neither patient had symptoms of
      thyrotoxicosis. Transient hyperthyroidism may be an under-recognized complication
      of total parathyroidectomy for tertiary hyperparathyroidism. These patients
      should be monitored with thyroid function tests and assessed for clinical signs
      attributable to thyrotoxicosis.

PMID- 18726671
TI  - Genetic analyses in a variant of Mayer-Rokitansky-Kuster-Hauser syndrome (MURCS
      association).
AB  - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by the congenital
      absence of uterus and upper part of the vagina as a result of Mullerian duct
      agenesis. The combination of MRKH syndrome with renal anomalies and
      cervicothoracic dysplasia is known as MURCS association (Mullerian aplasia, Renal
      anomalies, and Cervicothoracic Somite dysplasia). The etiology remains poorly
      understood. We delineate this disease by reporting on a 16-year-old patient
      showing the cardinal features of MURCS association accompanied by a persistent
      left superior vena cava and atrial septal defect, orofacial clefting, and mild
      reduction deformities of the left hand. Fluorescence in situ hybridization did
      not show major deletions or duplications of the DiGeorge/VCFS (velocardiofacial
      syndrome) region at chromosome 22q11.1 as well as the TBX5/TBX3 region at
      12q24.1. In addition, sequencing of the TP63L (p63) gene, residing at 3q27,
      remained normal in the presented patient. Thus, we provide further evidence for
      the genetic heterogeneity of MURCS association.

PMID- 18726673
TI  - Reconfiguring a hospital towards general practice: the case of Peamount.
AB  - BACKGROUND: The decline in incidence of tuberculosis in Ireland has led Peamount
      Hospital to reconfigure its services towards the needs of general practice. AIMS:
      To ascertain views of local GPs on their current use of Peamount, and how the
      hospital might best serve their future needs. METHODS: Self-administered postal
      questionnaires sent to 151 GPs practicing in Peamount's catchment area, to
      determine their current use of services, and likely future use of proposed
      services. Total valid response rate 64% (n = 84). RESULTS: Responses indicated a
      lack of awareness of many services currently available, with a concomitant under
      use of these services. The majority of GPs would use planned future services,
      particularly expanded radiology services. CONCLUSIONS: This survey promoted
      awareness among GPs of services available at Peamount. It informed the planning
      of future services and promoted a culture of involving local GPs in the planning
      of services of which they will be the users.

PMID- 18726672
TI  - [Chemotherapy for prostate cancer].
AB  - For many years the benefit of chemotherapy in patients with prostate cancer was
      thought to be limited to palliation of late-stage disease, and thus this
      treatment option only became involved in patient care towards the end of the
      disease process, if at all. However, two landmark phase-III trials with docetaxel
      based therapy (TAX 327 and Southwest Oncology Group, SWOG, 9916) have shown a
      survival benefit for patients with hormone refractory prostate cancer (HRPC) thus
      prompting a change in patterns of care. With raising interest for
      chemotherapeutic options and clinical trials for new drugs and new indications
      (neoadjuvant therapy, adjuvant therapy, increasing PSA levels after local
      treatment, and hormone sensitive cancer) under way our goal was to review within
      the context of a multidisciplinary team the available evidence and explore the
      standard for the medical treatment of prostate cancer outside of clinical trials.
      We are carefully evaluating the current treatment recommendations based on the
      available evidence and highlight potential future treatment options but also
      discuss important clinical topics (treatment until progression versus the
      advantage of chemo holidays, definition of particular patient subgroups and
      potential second line options) for which there are no clear cut answers to date.
      The role and importance of radiotherapy, biphosphonate treatment and the medical
      management of pain and side effects is also discussed. The multitude of treatment
      options for patients with advanced prostate cancer clearly asks for a close
      collaboration between urologists, medical oncologists and radiation therapists.

PMID- 18726674
TI  - Massive pulmonary embolism immediately diagnosed by transthoracic
      echocardiography and treated with tenecteplase fibrinolysis.
AB  - We report the case of a 75-year-old woman with new onset dyspnoea, hypotension,
      and right bundle branch block. Transthoracic echocardiography (TTE) showed a
      thrombus in the right pulmonary artery and acute pulmonary embolism was
      diagnosed. The patient immediately underwent fibrinolysis with tenecteplase, with
      prompt recovery of clinical conditions and ECG anomalies. Bedside TTE might be
      helpful for immediate diagnosis of massive PE needing rapid treatment by
      fibrinolysis.

PMID- 18726676
TI  - Drug therapy and personalized health care: pharmacogenomics in perspective.

PMID- 18726675
TI  - Myocardial oxidative stress, osteogenic phenotype, and energy metabolism are
      differentially involved in the initiation and early progression of delta
      sarcoglycan-null cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is a common cause of heart failure, and
      identification of early pathogenic events occurring prior to the onset of cardiac
      dysfunction is of mechanistic, diagnostic, and therapeutic importance. The work
      characterized early biochemical pathogenesis in TO2 strain hamsters lacking delta
      sarcoglycan. Although the TO2 hamster heart exhibits normal function at 1 month
      of age (presymptomatic stage), elevated levels of myeloperoxidase, monocyte
      chemotactic protein-1, malondialdehyde, osteopontin, and alkaline phosphatase
      were evident, indicating the presence of inflammation, oxidative stress, and
      osteogenic phenotype. These changes were localized primarily to the myocardium.
      Derangement in energy metabolism was identified at the symptomatic stage (4
      month), and is marked by attenuated activity and expression of pyruvate
      dehydrogenase E1 subunit, which catalyzes the rate-limiting step in aerobic
      glucose metabolism. Thus, this study illustrates differential involvement of
      oxidative stress, osteogenic phenotype, and glucose metabolism in the initiation
      and early progression of delta-sarcoglycan-null DCM.

PMID- 18726677
TI  - Comparative studies of two araceous lectins by steady state and time-resolved
      fluorescence and CD spectroscopy.
AB  - Transitions in the tryptophan microenvironment and secondary structure of two
      monocot lectins from Sauromatum guttatum and Arisaema tortuosum under different
      denaturing conditions were studied by steady state and time resolved fluorescence
      and CD spectroscopy. The lectins exist as tetramers with a single tryptophan
      residue estimated per monomer, present in a polar environment. Quenching with
      ionic quenchers showed predominantly electropositive environment for tryptophan
      residues. Acrylamide had maximum quenching effect. A decrease in KI quenching due
      to lectin denaturation indicated redistribution of charges as a result of
      possible conformational change. The two values for lifetimes of tryptophanyl
      population (1.2-1.4 and 6.3-6.4 ns) reduced substantially on quenching or
      denaturation. Similarly, both the lectins showed a drastic loss of secondary
      structure in 5 M Gdn-HCl or 6 M Urea or at pH 2.0 and below. For the first time
      araceous lectins, like legume lectins are shown to bind adenine. The presence of
      a compact structure at alkaline pH 10.0-12.0 was observed in CD spectra.

PMID- 18726679
TI  - IL-2 family of cytokines in T regulatory cell development and homeostasis.
AB  - INTRODUCTION: Interleukin 2 (IL-2) induces an essential signal for T regulatory
      (Treg) cells. Without a functional IL-2R, only immature CD4(+) Foxp3(low)
      CD25(neg) T cells develop, and these cells fail to suppress autoreactive T cells
      in the periphery. DISCUSSION: IL-2 functions during Treg cell development by
      upregulating Foxp3 and CD25 and by increasing the number of thymic Treg cells.
      Upon exiting the thymus during neonatal life, IL-2 is responsible for rapid
      amplification of the number of Treg cells in peripheral lymph nodes to insure
      suppression of autoreactive T cells that escape negative selection, thereby
      maintaining tolerance. The homeostasis of Treg cells in mature immunocompetent
      mice also depends on IL-2. However, there is an alternative mechanism for Treg
      cells homeostasis that may represent a minor IL-2-independent pathway or the
      consequence of weak and very transient IL-2R signaling. CONCLUSION: Thus, IL-2
      provides importance signals for Treg cell development and for their homeostasis
      in peripheral immune tissues.

PMID- 18726680
TI  - Distinguishing broad autism phenotype from schizophrenia-spectrum disorders.

PMID- 18726678
TI  - The evolving systemic and local biomarker milieu at different stages of disease
      progression in rat adjuvant-induced arthritis.
AB  - INTRODUCTION: Rats with adjuvant-induced arthritis (AIA) were necropsied on 14
      occasions during preclinical, acute clinical and chronic clinical stages of AIA
      progression to characterize local (joint protein extracts) and systemic (serum)
      levels of mediators regulating inflammation and bone erosion in conjunction with
      lymphoid tissue-specific leukocyte kinetics. RESULTS: Systemic increases in
      alpha1 acid glycoprotein, tumor necrosis factor-alpha (TNFalpha), interleukin
      (IL)-17, transforming growth factor beta (TGFbeta), and chemokine (C-C motif)
      ligand 2 (CCL2) together with local IL-1alpha/beta and TGFbeta enrichment and
      local lymphoid hyperplasia preceded the onset of clinical disease and joint
      damage. Systemic upregulation of TNFalpha, IL-6, IL-17, TGFbeta, IL-18, CCL2,
      receptor activator of nuclear factor-kappabeta ligand (RANKL), and prostaglandin
      E(2) during acute and/or chronic AIA coincided with systemic leukocytosis and
      CD4+ T cell increase in blood and spleen. In contrast, progression of joint
      erosions during clinical AIA was associated with intra-articular increases in IL
      1alpha/beta, IL-6, RANKL, IL-17, TGFbeta, CCL2, and KC/GRO and also a dramatic
      decline in osteoprotegerin. CONCLUSION: These data indicate that systemic and
      local events in inflammatory arthritis are discrete processes, driven by multiple
      cellular and humoral mediators with distinct kinetic profiles.

PMID- 18726681
TI  - Working memory in schizophrenia: an EEG study using power spectrum and coherence
      analysis to estimate cortical activation and network behavior.
AB  - This study examined regional cortical activations and cortico-cortical
      connectivity in a group of 20 high-functioning patients with schizophrenia and 20
      healthy controls matched for age and sex during a 0- and a 2-back working memory
      (WM) task. An earlier study comparing schizophrenia patients with education level
      matched healthy controls revealed less "optimally" organized network during the 2
      back task, whereas a second study with healthy volunteers had suggested that the
      degree of cortical organization may be inversely proportional to educational
      level (less optimal functional connectivity in better educated individuals
      interpreted as the result of higher efficiency). In the present study, both
      groups succeeded in the 2-back WM task although healthy individuals had generally
      attained a higher level of education. First absolute power spectrum of the
      different frequency bands corresponding to the electrodes of each lobe was
      calculated. Then the mean values of coherence were calculated as an index of the
      average synchronization to construct graphs in order to characterize local and
      large scale topological patterns of cortico-cortical connectivity. The power
      spectra analyses showed signs of hypofrontality in schizophrenics with an
      asymmetry. Additionally, differences between the groups with greater changes
      during WM in healthy individuals were visible in all lobes more on the left side.
      The graph parameter results indicated decreased small-world architecture i.e.
      less optimal cortico-cortical functional organization in patients as compared to
      controls. These findings are consistent with the notion of aberrant neural
      organization in schizophrenics which is nevertheless sufficient in supporting
      adequate task performance.

PMID- 18726682
TI  - Rapid vs. standard HIV testing in bathhouses: what is gained and lost?
AB  - Previous research demonstrates that standard voluntary counseling and testing
      (VCT) in bathhouses is feasible, and is an effective means for identifying new
      HIV cases and producing short term change in risk and precautionary behaviors.
      Less is known about whether the promise shown in standard VCT will be maintained
      as rapid testing is disseminated into outreach settings such as bathhouses. This
      study aimed to compare the risk and demographic profiles of men presenting for
      rapid vs. standard VCT in a bathhouse setting, and to explore the effectiveness
      of rapid VCT in identifying new infections and changing risk and precautionary
      behaviors. Bathhouse-based VCT was conducted over the course of two years--in the
      first year, 492 men participated in standard testing, and in the following year
      528 men from the same venue participated in rapid testing. Similar percentages of
      men were found to be positive using rapid and standard testing (2.5% and 3.7%,
      respectively), although rapid testing delivered results to more individuals than
      standard testing (97% vs. 71%). Convenience samples of 133 of the standard
      testers and 161 of the rapid testers were obtained and assessed at two points:
      immediately prior to and 3 months after testing. The risk and demographic
      profiles of men participating in standard vs. rapid testing were similar,
      suggesting that rapid testing is as feasible an approach as standard testing for
      attracting men with recent histories of HIV-related risk behavior. In the 3
      months following rapid VCT, some risk and precautionary behaviors were changed
      compared to pre-VCT, but effects were smaller than in the previous study of
      standard VCT.

PMID- 18726683
TI  - Analysis of expressed sequence tags (ESTs) from Agrostis species obtained using
      sequence related amplified polymorphism.
AB  - Bentgrass (Agrostis spp.), a genus of the Poaceae family, consists of more than
      200 species and is mainly used in athletic fields and golf courses. Creeping
      bentgrass (A. stolonifera L.) is the most commonly used species in maintaining
      golf courses, followed by colonial bentgrass (A. capillaris L.) and velvet
      bentgrass (A. canina L.). The presence and nature of sequence related amplified
      polymorphism (SRAP) at the cDNA level were investigated. We isolated 80 unique
      cDNA fragment bands from these species using 56 SRAP primer combinations.
      Sequence analysis of cDNA clones and analysis of putative translation products
      revealed that some encoded amino acid sequences were similar to proteins involved
      in DNA synthesis, transcription, and signal transduction. The cytosolic
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene (GenBank accession no.
      EB812822) was also identified from velvet bentgrass, and the corresponding
      protein sequence is further analyzed due to its critical role in many cellular
      processes. The partial peptide sequence obtained was 112 amino acids long,
      presenting a high degree of homology to parts of the N-terminal and C-terminal
      regions of cytosolic phosphorylating GAPDH (GapC). The existence of common
      expressed sequence tags (ESTs) revealed by a minimum evolutionary dendrogram
      among the Agrostis ESTs indicated the usefulness of SRAP for comparative genome
      analysis of transcribed genes in the grass species.

PMID- 18726684
TI  - Molecular characterization and expression pattern of the porcine STARS, a
      striated muscle-specific expressed gene.
AB  - STARS (striated muscle activator of Rho signaling) promotes the nuclear
      localization of MRTFs and mediates SRF transcription, which provides a potential
      muscle-specific mechanism for linking changes in the actin cytoskeleton structure
      with muscle gene expression. In this study, the full-length cDNA of the porcine
      STARS was cloned. The open reading frame of this gene contains 1,155 bp and
      encodes a protein of 384 amino acids, which is 79, 73, and 77% identical with
      human, mouse, and rat STARS genes, respectively. RT-PCR revealed that STARS is
      specifically expressed in heart and skeletal muscles. STARS is also distinctly
      different in different muscle developmental stages. The result indicates that its
      expression increased gradually from 33 dpc (days postcoitum) to postnatal
      muscles, and peaked 28 days postnatal. The porcine STARS was mapped to SSC4p13
      using the somatic cell hybrid panel and the radiation hybrid panel IMpRH (LOD
      score 11.98). The data show that STARS is closely linked to marker SW871. A T/G
      single nucleotide polymorphism in the coding sequence, detected as Bsh1236I PCR
      RFLP, displays allele frequency differences in six pig breeds.

PMID- 18726685
TI  - Polymorphic variants of extracellular superoxide dismutase gene in a Romanian
      population with atheroma.
AB  - Extracellular superoxide dismutase (EC-SOD) is the main SOD isoform in the
      arterial wall contributing to cardiovascular defense against oxidative stress by
      removing the superoxide anion. In our study, the Thr40Ala and Arg213Gly
      polymorphic variants of the EC-SOD gene (SOD ( 3 )) were investigated for
      associations with atherosclerosis and other related factors in 144 subjects with
      significant atheroma (having one, two, or three major coronary arteries with >50%
      obstruction, and/or peripheral artery lesions, and/or carotid artery stenosis
      demonstrated by angiography and echography) and in 150 subjects with no
      significant atheroma. For the Arg213Gly polymorphism, only five heterozygous
      subjects were found. Although the difference in the genotype distribution for the
      Thr40Ala polymorphism was not statistically significant between patients with
      atheroma (AA 49.3%, AG 34.7%, GG 16.0%) and those without significant atheroma
      (AA 41.3%, AG 43.3%, GG 15.3%), there was an association of the Thr40 allele with
      diabetes (P = 0.03) and hypertension (P = 0.04).

PMID- 18726686
TI  - Analysis of HLA DR2&DQ6 (DRB1*1501, DQA1*0102, DQB1*0602) haplotypes in Iranian
      patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) is prototype of inflammatory demyelinating disease of the
      central nervous system .The etiology of MS remains unclear, but according to
      current data the disease develops in genetically susceptible individuals and may
      require additional environmental triggers. The human leukocyte antigen (HLA)
      class II alleles (DRB1*1501, DQA1*0102, DQB1*0602) may have the strongest genetic
      effect in MS. In this study, the role of these alleles were investigated in 183
      Iranian patients with multiple sclerosis and compared with 100 healthy
      individuals. HLA typing for DRB1*1501, DQA1*0102, DQB1*0602 was performed by
      polymerase chain reaction (PCR) amplification with sequence-specific primers (PCR
      SSP) method. The results show that, HLA DR B1*1501 was significantly more
      frequent among MS patients (46% vs. 20%, PV = 0.0006) but DQA1*0102 haplotype was
      negatively associated with MS (30% vs. 50%, PV = 0.0049) and no significant
      association was found with DQB1*0602 and MS patients in comparison with control
      group (24% and 30%, PV = 0.43). No significant correlation was observed among
      these alleles with sex, type of disease; initial symptoms, expanded disability
      status scale (EDSS), as well as age at onset and familial MS. This study
      therefore indicates that there is no association of above HLA haplotypes with
      clinical presentation, disease duration, and disability in Iranian patients with
      MS which is in line with other previous studies in different ethnic groups.

PMID- 18726688
TI  - Biofeedback treatment for headache disorders: a comprehensive efficacy review.
AB  - The aim of the present review was to critically evaluate the documented evidence
      regarding the efficacy of biofeedback for the two most prevalent headache
      conditions--migraine and tension-type headache. Drawing upon two recently
      published meta-analyses, data from 150 outcome studies, including randomized
      controlled trials as well as uncontrolled quasi-experimental designs, were
      screened. Of these, 94 studies were selected for inclusion according to
      predefined criteria. Meta-analytic integrations were carried out separately for
      the two conditions of interest. The main results were medium-to-large mean effect
      sizes for biofeedback in adult migraine and tension-type headache patients.
      Treatment effects remained stable over an average follow-up period of 14 months,
      both in completer and intention-to-treat analyses. Headache frequency was the
      primary outcome variable and showed the largest improvements. Further significant
      effects were shown for perceived self-efficacy, symptoms of anxiety and
      depression, and medication consumption. Reduced muscle tension in pain related
      areas was observed in electromyographic feedback for tension-type headache.
      Biofeedback was more effective than waiting list and headache monitoring
      conditions in all cases, while electromyographic feedback for tension-type
      headache showed additional significant effects over placebo and relaxation
      therapies. Levels of efficacy (migraine: efficacious, level 4; tension-type
      headache: efficacious and specific, level 5) and recommendations for future
      research are provided.

PMID- 18726687
TI  - Hemolysate-induced expression of intercellular adhesion molecule-1 and monocyte
      chemoattractant protein-1 expression in cultured brain microvascular endothelial
      cells via through ROS-dependent NF-kappaB pathways.
AB  - In order to determine the possible effects of hemolysate on brain microvascular
      endothelial cells (BMECs), we examined the effects of hemolysate on the
      expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte
      chemoattractant protein-1 (MCP-1), generation of reactive oxygen species (ROS),
      and NF-kappaB activation in rat BMECs. Hemolysate induced the expression of ICAM
      1 and MCP-1 in endothelial cells. In addition, hemolysate stimulated nuclear
      translocation of the p65 subunit of NF-kappaB, and NF-kappaB DNA-binding activity
      in BMECs. Furthermore, hemolysate increased ROS generation, and hemolysate
      induced ICAM-1and MCP-1 expression and NF-kappaB activation were abrogated in the
      presence of the direct scavenger of ROS. Taken together, our results indicate
      that hemolysate can induce inflammatory responses that increase expression of
      ICAM-1 and MCP-1, through ROS-dependent NF-kappaB activation in BMECs.

PMID- 18726689
TI  - Temporomandibular disorders and facial pain: a psychophysiological perspective.
AB  - This article presents a psychophysiological perspective on temporomandibular
      muscle and joint disorders (TMJD) and facial pain. After a brief introduction to
      TMJD, the article presents data, largely derived from work carried out in my
      laboratory, that address four questions: (1) What are the consequences of
      parafunctional activities? (2) Do TMJD patients engage in parafunctional
      activities? (3) Why are TMJD patients unaware of these activities? and (4) What
      are the implications of these findings for treatment? The findings suggest that
      low-level parafunctions increase pain in otherwise pain-free individuals and can
      produce symptoms sufficiently severe to meet the diagnostic criteria for TMJD
      diagnoses of myofascial pain and/or arthralgia. Patients with certain forms of
      TMJD report very high levels of parafunctional tooth contact. Their lack of
      awareness of these behaviors may arise from uncertain definitions of the term
      "clenching", from proprioceptive deficits, or from the presence of adjunctive
      behaviors. Preliminary work shows that reduction in tooth contact via habit
      reversal techniques may be a promising mechanism for reducing pain in these
      patients.

PMID- 18726690
TI  - Novel oligosaccharide has suppressive activity against human leukemia cell
      proliferation.
AB  - Various oligosaccharides containing galactose(s) and one glucosamine (or N
      acetylglucosamine) residues with beta1-4, alpha1-6 and beta1-6 glycosidic bond
      were synthesized; Galbeta1-4GlcNH(2), Galalpha1-6GlcNH(2), Galalpha1-6GlcNAc,
      Galbeta1-6GlcNH(2), Galbeta1-4Galbeta1-4GlcNH(2) and Galbeta1-4Galbeta1-4GlcNAc.
      Galalpha1-6GlcNH(2) (MelNH(2)) and glucosamine (GlcNH(2)) had a suppressive
      effect on the proliferation of K562 cells, but none of the other saccharides
      tested containing GlcNAc showed this effect. On the other hand, the proliferation
      of the human normal umbilical cord fibroblast was suppressed by none of the
      saccharides other than GlcNH(2). Adding Galalpha1-6GlcNH(2) or glucosamine to the
      culture of K562 cell, the cell number decreased strikingly after 72 h. Staining
      the remaining cells with Cellstain Hoechst 33258, chromatin aggregation was found
      in many cells, indicating the occurrence of cell death. Furthermore, all of the
      cells were stained with Galalpha1-6GlcNH-FITC (MelNH-FITC). Neither the control
      cells nor the cells incubated with glucosamine were stained. On the other hand,
      when GlcNH-FITC was also added to cell cultures, some of them incubated with
      Galalpha1-6GlcNH(2) were stained. The difference in the stainability of the K562
      cells by Galalpha1-6GlcNH-FITC and GlcNH-FITC suggests that the intake of
      Galalpha1-6GlcNH(2) and the cell death induced by this saccharide is not same as
      those of glucosamine. The isolation of the Galalpha1-6GlcNH(2) binding protein
      was performed by affinity chromatography (melibiose-agarose) and LC-MS/MS, and we
      identified the human heterogeneous ribonucleoprotein (hnRNP) A1 (34.3 kDa)
      isoform protein (30.8 kDa). The hnRNP A1 protein was also detected from the
      eluate(s) of the MelNH-agarose column by the immunological method (anti-hnRNP-A1
      and HRP-labeled anti-mouse IgG (gamma) antibodies).

PMID- 18726692
TI  - Patient and family advocacy: working with individuals with comorbid mental
      illness and developmental disabilities and their families.
AB  - There are many factors to consider when working with individuals with mental
      illness and developmental disabilities and their families. Working in
      collaboration with individuals and their families using a patient- and family
      centered care approach is vital. This approach informs the professional's values
      and practice patterns thereby allowing them to help the individual and family
      deal with common challenges and stresses such as establishing relationships with
      care providers, ensuring coordination of care, family concerns, knowledge of
      important systems of care, and the need for advocacy.

PMID- 18726691
TI  - Revealing the anti-HRP epitope in Drosophila and Caenorhabditis.
AB  - Antibodies are very often used as specific cell and/or tissue markers. An example
      of this is anti-horseradish peroxidase (HRP), an antibody raised against a plant
      glycoprotein, which was shown some twenty-five years ago to specifically stain
      neural tissue in an animal, Drosophila melanogaster. This peculiar finding was
      later expanded to other invertebrate species including Caenorhabditis elegans,
      which were also shown to bear anti-HRP epitopes. Initial experiments indicated
      that the epitopes recognised by anti-HRP in invertebrates are of carbohydrate
      nature. Indeed, more recent experiments have characterised relevant core alpha1-3
      fucosylated N-glycan structures that act as epitopes in various model and
      parasitic organisms. Moreover, a number of enzymes required for the synthesis of
      such structures have been identified. Over the years, medically-relevant roles of
      these structures have become apparent as regards allergenicity and
      immunoregulation. Although major advances have been made in understanding of the
      underlying mechanisms and structures related to the anti-HRP epitope, the in vivo
      role of the relevant epitopes in neural and other tissues is yet to be resolved.
      Current understanding of the anti-HRP epitopes synthesis and their relevance is
      discussed and elaborated.

PMID- 18726693
TI  - Variation in contents of total phenolics and flavonoids and antioxidant
      activities in the leaves of 11 Eriobotrya species.
AB  - Eriobotrya plants are known to have significant amounts of phenolics and
      flavonoids, and exhibit a strong antioxidant activity. Experiments were conducted
      to examine variation in the contents of total phenolics and flavonoids, and
      antioxidant activities in the leaves of 11 Eriobotrya species (Tibet loquat,
      Daduhe loquat, Hengchun loquat, Taiwan loquat, Oak leaf loquat, Bengal loquat,
      Fragrant loquat, Guangxi loquat, Obovate loquat, Big flower loquat, and common
      loquat, the last species include two materials, one is a cultivar 'Zaozhong 6',
      another is a wild tree). In these species, 'Zaozhong 6' loquat is a cultivar. The
      leaf extracts of 'Tibet', 'Obovate', 'Taiwan', 'Bengal' and 'Hengchun' loquats
      exhibited significantly higher contents of total flavonoids and total phenolics,
      compared with those of other species. Of these 11 species, the highest contents
      of total phenolics and total flavonoids were observed in 'Tibet' and 'Obovatae'
      loquats, respectively. The significantly stronger antioxidant abilities assessed
      by the DPPH radical scavenging activity and reducing power were obtained in the
      leaf extracts of 'Taiwan', 'Tibet', 'Bengal', 'Oak leaf', 'Hengchun' and
      'Obovate' loquats, compared with the other species. In addition, significant
      correlations were found between the contents of total phenolics or flavonoids and
      DPPH radical scavenging activity/reducing power. This work indicates that the
      leaf extracts of the wild Eriobotrya species, 'Tibet', 'Obovatae', 'Taiwan',
      'Bengal', 'Oak leaf' and 'Hengchun' loquats, exhibited significantly higher
      levels of total phenolics and flavonoids, and significantly stronger antioxidant
      activities, compared with the cultivated species, 'Zaozhong 6' loquat, which
      suggests that these wild species have a better utilization value.

PMID- 18726695
TI  - Research on transition to adulthood: building the evidence base to inform
      services and supports for youth and young adults with serious mental health
      disorders.
AB  - Since the mid-1990s, research has established a clear picture of the poor real
      life outcomes achieved by transition-age youth and young adults who have been
      diagnosed with a serious mental health disorder. The purpose of this article is
      to: (1) introduce the reader to the other eight articles in this special issue on
      Transition to Adulthood Research; (2) illustrate how each is contributing to the
      research base available to more fully understand these challenges as well as
      guide the creation of developmentally appropriate and effective services and
      supports for youth and young adults and their families; and (3) suggest future
      directions for continuing to advance this field of research and program
      implementation to improve outcomes though practice and policy improvements.

PMID- 18726694
TI  - Clinical spectrum of premature pubarche: links to metabolic syndrome and ovarian
      hyperandrogenism.
AB  - Premature pubarche-defined as the appearance of pubic hair before age 8 years in
      girls and 9 years in boys-has been traditionally considered a benign entity.
      However, recent evidence supports the notion that premature pubarche in girls may
      be a forerunner of the metabolic syndrome, and may precede the development of
      clinical ovarian androgen excess in adolescence. This sequence seems to occur
      more frequently when premature pubarche was preceded by reduced fetal growth and
      followed by excessive postnatal catch-up in height and particularly in weight;
      hyperinsulinemia appears to be a key factor in the development of this sequence
      of events. In girls with premature pubarche and a history of a low birth weight,
      puberty tends to start earlier and to have a faster course, so that final height
      may be moderately reduced. In these girls, metformin therapy may reverse the
      progression to clinical ovarian hyperandrogenism, normalize body composition and
      excess visceral fat, and delay pubertal progression without attenuating linear
      growth and bone mineralization, suggesting that adult height may be improved.
      Long-term follow-up of these patients is needed to fully determine the ultimate
      effects of insulin sensitization as well as the maintenance of these benefits
      after discontinuation of therapy.

PMID- 18726696
TI  - Comprehension of humor in children with nonverbal learning disabilities, reading
      disabilities, and without learning disabilities.
AB  - The normal development of humor in children has been well documented with a
      predictable course that is tied to social, cognitive, and linguistic development
      in children. This study explored humor comprehension in children with nonverbal
      learning disabilities (NVLD). Children with NVLD were compared with children with
      reading disabilities and a comparison group of children with no learning
      disabilities to assess their comprehension of humor. The humor test was composed
      of a joke and cartoon section. No group differences in humor comprehension were
      found when the NVLD group was defined as having visual-spatial and visual
      reasoning deficits. However, when the NVLD group was divided into children with
      and without social perceptual difficulties as defined by a direct measure of
      social comprehension, significant group differences were found in the levels of
      humor comprehension. These results support the association of humor comprehension
      with social perception and lend tentative support to the hypothesis that children
      with NVLD may not be a homogenous group. Future study directions include further
      exploration into the nature of the association between humor comprehension and
      social perception as well as closer examination of the heterogeneity of NVLD.

PMID- 18726698
TI  - Evaluation of a scaling approach for the bioequivalence of highly variable drugs.
AB  - Various approaches for evaluating the bioequivalence (BE) of highly variable
      drugs (CV > or = 30%) have been debated for many years. More recently, the FDA
      conducted research to evaluate one such approach: scaled average BE. A main
      objective of this study was to determine the impact of scaled average BE on study
      power, and compare it to the method commonly applied currently (average BE).
      Three-sequence, three period, two treatment partially replicated cross-over BE
      studies were simulated in S-Plus. Average BE criteria, using 80-125% limits on
      the 90% confidence intervals for C (max) and AUC geometric mean ratios, as well
      as scaled average BE were applied to the results. The percent of studies passing
      BE was determined under different conditions. Variables tested included within
      subject variability, point estimate constraint, and different values for
      sigma(w0), which is a constant set by the regulatory agency. The simulation
      results demonstrated higher study power with scaled average BE, compared to
      average BE, as within subject variability increased. At 60% CV, study power was
      more than 90% for scaled average BE, compared with about 22% for average BE. A
      sigma(w0) value of 0.25 appears to work best. The results of this research
      project suggest that scaled average BE, using a partial replicate design, is a
      good approach for the evaluation of BE of highly variable drugs.

PMID- 18726699
TI  - Natural enemies of mass-reared predatory mites (family Phytoseiidae) used for
      biological pest control.
AB  - Predatory mites of the family Phytoseiidae are valued natural enemies that
      provide effective pest control in greenhouses and on agricultural crops. Mass
      reared phytoseiids are occasionally associated with microorganisms and although
      their effects are not always apparent, some are pathogenic and reduce host
      fitness. Invertebrate pathogens are encountered more frequently in mass
      production systems than in nature because rearing environments often cause
      overcrowding and other stresses that favour pathogen transmission and increase an
      individual's susceptibility to disease. Although unidentified microorganisms have
      been reported in phytoseiids, bacteria and microsporidia have been detected with
      considerable frequency. The bacterium Acaricomes phytoseiuli is associated with
      an accumulation of birefringent crystals in the legs of Phytoseiulus persimilis
      and infection reduces the fitness of this spider mite predator. Wolbachia,
      detected in Metaseiulus occidentalis and other phytoseiids, may cause cytoplasmic
      incompatibilities that affect fecundity. However, the effects of Rickettsiella
      phytoseiuli on P. persimilis are unknown. Microsporidia are spore-forming
      pathogens that infect Neoseiulus cucumeris, N. barkeri, M. occidentalis and P.
      persimilis. Microsporidia cause chronic, debilitating disease and these pathogens
      often remain undetected in mass-rearings until a decrease in productivity is
      noticed. Routine screening of individuals is important to prevent diseased mites
      from being introduced into existing mass-rearings and to ensure that mite
      populations remain free from pathogens. The means by which bacteria and
      microsporidia are detected and strategies for their management in phytoseiid mass
      rearings are discussed.

PMID- 18726697
TI  - CNS delivery via adsorptive transcytosis.
AB  - Adsorptive-mediated transcytosis (AMT) provides a means for brain delivery of
      medicines across the blood-brain barrier (BBB). The BBB is readily equipped for
      the AMT process: it provides both the potential for binding and uptake of
      cationic molecules to the luminal surface of endothelial cells, and then for
      exocytosis at the abluminal surface. The transcytotic pathways present at the BBB
      and its morphological and enzymatic properties provide the means for movement of
      the molecules through the endothelial cytoplasm. AMT-based drug delivery to the
      brain was performed using cationic proteins and cell-penetrating peptides (CPPs).
      Protein cationization using either synthetic or natural polyamines is discussed
      and some examples of diamine/polyamine modified proteins that cross BBB are
      described. Two main families of CPPs belonging to the Tat-derived peptides and
      Syn-B vectors have been extensively used in CPP vector-mediated strategies
      allowing delivery of a large variety of small molecules as well as proteins
      across cell membranes in vitro and the BBB in vivo. CPP strategy suffers from
      several limitations such as toxicity and immunogenicity--like the cationization
      strategy--as well as the instability of peptide vectors in biological media. The
      review concludes by stressing the need to improve the understanding of AMT
      mechanisms at BBB and the effectiveness of cationized proteins and CPP-vectorized
      proteins as neurotherapeutics.

PMID- 18726700
TI  - Expression of glucose transporter 1 is associated with loss of heterozygosity of
      chromosome 1p in oligodendroglial tumors WHO grade II.
AB  - Objective Oligodendroglial tumors with a loss of heterozygosity of 1p (LOH1p)
      appear to have a better prognosis than oligodendrogliomas without LOH.
      Previously, we reported glucose uptake in low-grade oligodendroglial tumors to be
      related to LOH 1p status. Here, we performed an immunohistochemical study of the
      common glucose transporters (GLUT) in relation to LOH1p. Material and methods We
      examined 17 oligodendrogliomas (O II, 11 with LOH1p), 16 oligoastrocytomas (OA
      II, 5 with LOH1p) and 7 astrocytomas (A II, none with LOH1p). Confocal microscopy
      was performed for p53, GLUT-1, -3 and -12. Immunoreaction was rated
      semiquantitatively by percentage of positive cells and staining intensity on
      immunohistological stainings. Results Confocal microscopy depicted immunoreaction
      for GLUT-1, -3 and -12 in the cytoplasm of the tumor cells. Oligodendrogliomas
      revealed a lower immunoreactivity for GLUT-1 than oligoastrocytomas and
      astrocytomas (P = 0.0263). No differences in immunoreactivity were found for GLUT
      3 and GLUT-12. GLUT-1 expression in tumors with LOH 1p was significantly lower
      than in tumors with wild type 1p status (P = 0.0017). GLUT-3 and GLUT-12
      immunoreactivity was not correlated with LOH 1p. Conclusion Expression of GLUT-1
      is significantly reduced in low-grade oligodendroglial tumors harboring LOH 1p.
      Further studies should address the functional role of GLUT-1 in regard to
      chemosensitivity of oligodendrogliomas.

PMID- 18726701
TI  - Monitoring the effect of urban green areas on the heat island in Athens.
AB  - The role of urban green areas in the microclimatic conditions of cities, during
      summer, is investigated in this paper through monitoring campaigns carried out at
      the National garden, at the city centre of Athens. Two types of investigations
      were carried out: i) a microscopic one that investigated the thermal conditions
      inside the Garden and the immediate surrounding urban area and ii) a macroscopic
      one that compared the temperature profile of the Garden with that of the greater
      city centre area. It was concluded that in microscopic level, the temperature
      profile inside the National Garden and the immediate surrounding urban area did
      not showed a clear evidence of the influence of the Garden and it was dependent
      on the characteristics of each location. In a macroscopic scale, the Garden was
      found cooler than the other monitored urban locations and temperature differences
      were mainly greater during the night, especially in streets with high building
      height to street width (H/W) ratio and low traffic, while in streets with high
      anthropogenic heat during the day, the biggest temperature differences were
      recorded during the day.

PMID- 18726702
TI  - Numerical simulation on pollutant dispersion from vehicle exhaust in street
      configurations.
AB  - The impact of the street configurations on pollutants dispersion from vehicles
      exhausts within urban canyons was numerically investigated using a computational
      fluid dynamics (CFD) model. Three-dimensional flow and dispersion of gaseous
      pollutants were modeled using standard kappa - epsilon turbulence model, which
      was numerically solved based on Reynolds-averaged Navier-Stokes equations by the
      commercial CFD code FLUENT. The concentration fields in the urban canyons were
      examined in three cases of street configurations: (1) a regular-shaped
      intersection, (2) a T-shaped intersection and (3) a Skew-shaped crossing
      intersection. Vehicle emissions were simulated as double line sources along the
      street. The numerical model was validated against wind tunnel results in order to
      optimize the turbulence model. Numerical predictions agreed reasonably well with
      wind tunnel results. The results obtained indicate that the mean horizontal
      velocity was very small in the center near the lower region of street canyon. The
      lowest turbulent kinetic energy was found at the separation and reattachment
      points associated with the corner of the down part of the upwind and downwind
      buildings in the street canyon. The pollutant concentration at the upwind side in
      the regular-shaped street intersection was higher than that in the T-shaped and
      Skew-shaped street intersections. Moreover, the results reveal that the street
      intersections are important factors to predict the flow patterns and pollutant
      dispersion in street canyon.

PMID- 18726703
TI  - Albendazole enantiomeric metabolism and binding to cytosolic proteins in the
      liver fluke Fasciola hepatica.
AB  - Fascioliasis causes important economic losses in ruminant species all over the
      world. Its control is largely based on the use of the flukicidal compound
      triclabendazole (TCBZ). However, its chemically related benzimidazole
      anthelmintic albendazole (ABZ) is being successfully used to control TCBZ
      resistance flukes. This research gains some insights into the comparative
      molecular behaviour of both anthelmintics within the target fluke. The goals of
      the current work were: (i) to assess the competitive binding of ABZ and TCBZ to
      cytosolic proteins of F. hepatica, and (ii) to evaluate the enantioselective
      biotransformation of ABZ in microsomal fractions obtained from TCBZ-susceptible
      and TCBZ-resistant strains of the liver fluke. Cytosolic proteins from fluke
      specimens bound TCBZ with greater affinity (83%) than ABZ (44%) and the fraction
      of TCBZ bound to cytosolic proteins was not displaced by ABZ. The microsomes from
      both -susceptible and resistant flukes sulphoxidized ABZ into ABZ sulphoxide
      (ABZSO). However, this oxidative activity was 49% higher in microsomes from TCBZ
      resistant flukes (P < 0.001) with a predominant production of the (+) ABZSO
      enantiomer. As earlier shown for TCBZ, the results reported here confirm an
      enhanced ability for ABZ oxidation in TCBZ-resistant flukes. While this enhanced
      oxidative metabolism of ABZ may cooperate to the resistance phenomenon, other
      pharmacodynamic-based mechanisms may be involved, which would explain why,
      although being chemically-related, ABZ remains efficacious against TCBZ resistant
      flukes under field conditions.

PMID- 18726704
TI  - Biological effects of FoxJ2 over-expression.
AB  - As reported previously, we have extensively studied FoxJ2, a member of the Fork
      Head transcription factors family. While the biochemical and functional
      structures of this transcription factor are well understood, its biological
      function remains unknown. Here, we present data that address this point using
      transgenic mouse technology. We found that the birth rate and the number of
      transgenic animals obtained when transferring embryos over-expressing the FoxJ2
      protein were lower than those obtained with embryos over-expressing a control
      protein, suggesting FoxJ2 overexpression has a negative effect on embryonic
      development. Transient FoxJ2 transgenesis experiments have confirmed that FoxJ2
      over-expression has a lethal effect on embryonic development from E10.5.
      Moreover, in vitro culture of FoxJ2-microinjected embryos demonstrated a
      significant developmental blockage, indicating that FoxJ2 could also have an
      effect on pre-implantation stages. Most probably, these negative effects of FoxJ2
      over-expression during development also explain the low percentage of adult
      transgenic mice obtained. Furthermore, most of the transgenic mice that lived to
      adulthood did not show transgene expression. In fact, the only two adult
      transgenic animals (one male and one female) in which FoxJ2 transgene expression
      was detected showed a mosaic expression and died prematurely as a result of
      cardio-respiratory failure. Postmortem analysis of these animals revealed a
      hypertrophic heart and abnormal testes in the male. In order to identify genes
      regulated by FoxJ2 consistent with the phenotypes observed for FoxJ2 transgenic
      mice, EMSA assays and co-transfection experiments were carried out. Our data
      indicate that the genes coding for the gap junction protein Connexin-43 and the
      cell-cell contact protein E-Cadherin, may be good candidates for FoxJ2-regulated
      genes. Interestingly, Connexin-43 and E-Cadherin show expression patterns similar
      to FoxJ2, and the phenotypes of Connexin-43 and E-Cadherin mutants resemble those
      of our FoxJ2 transgenic animals. These data suggest that the lethal effect on
      embryonic development of FoxJ2 overexpression, as well as the alterations
      observed in the heart and testes of adult transgenic mice, could be determined by
      changes in the transcription of genes such as Connexin-43 and/or E-Cadherin.

PMID- 18726706
TI  - Effect of doe milking and supplementation using Dichrostachys cinerea pods on kid
      and doe performance in grazing goats during the dry season.
AB  - Effects of supplementation and milking of Matebele does four weeks pre-partum to
      weaning, on milk yield, kid birth weight and growth rate were studied. Forty does
      were divided into four treatments: supplemented and milked (SM), supplemented and
      not milked (SNM), not supplemented and milked (NSM); and not supplemented and not
      milked (NSNM). Supplemented goats were given 200 g/doe/day of Dichrostachys
      cinerea pods containing 19% CP. The study was carried out in September during
      time of feed unavailability and animals were grazed on rangelands for seven hours
      before being given the supplement. Fifty-six kids were born from all the
      experimental animals and 24 were singles whereas 32 were twins. Milk yield was
      higher (P < 0.05) in supplemented than non-supplemented does. Although
      supplementation had no effect on kid birth weights, growth rates were higher (P <
      0.05) in the SNM group (103 +/- 10.1 g/day) than in the SM group (74 +/- 10.8
      g/day). Among the non-supplemented groups, kids from milked does had higher (P <
      0.05) daily gains (85 +/- 10.9 g/day) than those from non-milked does (67 +/-
      10.7 g/day). Weaning weights were higher (P < 0.05) in SNM does (12.8 +/- 1.30
      g/day) than in the SM does (10.2 +/- 1.17 g/day). Among kids from the non
      supplemented does, those from milked does had superior (P < 0.05) weaning weights
      (11.2 +/- 1.23 g/day) than those from non - milked does (9.2 +/- 1.27 g/day).
      Mortalities were also lowest in kids born from SNM does. It is concluded that pre
      partum to weaning supplementation generally increases milk production which then
      increases kids growth rates and weaning weights, as well as reduce kid
      mortalities.

PMID- 18726705
TI  - Risk factors for Mycobacterium avium subspecies paratuberculosis in Fars province
      (Southern Iran) dairy herds.
AB  - A cross-sectional study was conducted from March to August 2006 in dairy herds in
      Fars province, southern Iran to determine the herd-level risk factors for
      infection with Mycobacterium avium subspecies paratuberculosis (MAP). Statistical
      analysis using multivariable logistic regression showed that contamination of
      udders of periparturient cows with manure (OR = 6.4, P = 0.02) and history of
      having suspected cases of Johne's disease in the herd (OR = 6.7, P = 0.04) were
      significantly associated with the herd infection status. No relationship between
      breed, herd size and other management practices with the infection status of the
      herd were found in this study. Implementing high sanitary measures in the farm,
      particularly with respect to manure handling and cleaning could be considered as
      one of the important aspects in controlling disease in the region as well as in
      the future educational effort.

PMID- 18726707
TI  - The extreme arrogance of anti-aging medicine.
AB  - The anti-aging medicine movement proposes to alter the human body in order to
      achieve extreme longevity. To do this it has to reverse or by-pass the multiple
      causes of human aging. These include a large number of age-associated
      pathologies, each of which is being studied in great detail in research
      laboratories around the world. The protagonists of anti-aging medicine claim that
      it will be far more successful than the combined efforts of the innumerable
      scientists carrying out this research. Aging has an extremely long evolutionary
      history, and the anatomical structure and physiology of animals is directly
      related to their finite lifespan. The anti-aging movement proposes in a few
      decades to reverse what has been the result of millions of years of evolution.

PMID- 18726708
TI  - Stanley L. Miller (1930--2007): reflections and remembrances.
AB  - An appreciation of Stanley L. Miller, the pioneer prebiotic chemist, who died
      last year.

PMID- 18726709
TI  - Defining myocardial infarction by cardiac computed tomography.

PMID- 18726710
TI  - The baseline characteristics did not differ significantly.

PMID- 18726711
TI  - Familial nasopharyngeal carcinoma in Hong Kong: epidemiology and implication in
      screening.
AB  - The pathogenetic mechanism of nasopharyngeal carcinoma (NPC) is still unclear.
      Its familial aggregation, on the other hand, has been well documented by many
      epidemiological studies. The objective of this study was to evaluate the clinical
      characteristics of familial NPC in an endemic region. Between March 1994 and
      November 2005, 1,202 consecutive patients were treated at our institution.
      Patients were divided into 2 groups according to their family history: group 1
      had at least one first-degree relative with NPC at the time of diagnosis, and
      group 2 did not. There were 125(10.4%) patients in group 1, 66% of them had
      diseased siblings, 44% had diseased parents and 2% had diseased offspring. The
      patients in group 1 were on average about 2 years younger than group 2 at
      diagnosis (47.9 vs. 49.8, P = 0.04). There were also more stage I-II patients in
      group 1 (38 [corrected] vs. 23%, P < 0.01). Although the 5 year overall survival
      was also higher with group 1 (79 vs. 69%, P < 0.01), only age, sex, T
      classification and N classification were found to be significant independent
      factors but not family history per se (P = 0.10). Similar findings were observed
      after excluding screen-detected patients from group 1. The high incidence of
      familial clustering and improved outcomes from early detection highlight the
      importance of screening among these high risk family members.

PMID- 18726712
TI  - Heat shock protein 90 is involved in regulation of hypoxia-driven proliferation
      of embryonic neural stem/progenitor cells.
AB  - Hypoxia may regulate the proliferation of diverse stem cells. Our previous study
      showed that hypoxia promoted the proliferation of embryonic neural
      stem/progenitor cells (NPCs) and that hypoxia inducible factor-1(HIF-1) was
      critical in this process. HIF-1 could be stabilized under hypoxic conditions, and
      heat shock protein 90 (HSP90) is an essential protein that controls the activity
      and stabilization of HIF-1alpha. In the present work, we investigate whether
      HSP90 is involved in proliferation of NPCs under hypoxia by regulating HIF-1alpha
      stabilization. Geldanamycin (GA), an HSP90 inhibitor, decreased the expression of
      HIF-1alpha in NPCs during hypoxia-driven proliferation and reduced the expression
      level of HIF-1alpha protein under hypoxia in a time-dependent manner. The
      proliferation of NPCs induced by hypoxia was inhibited after GA treatment for 24
      h. Another HSP90 inhibitor, radicicol, had the same effect on NPCs as GA.
      Furthermore, the expression of erythropoietin (EPO) and vascular endothelial
      growth factor (VEGF) in NPCs under hypoxia was suppressed by GA. The above data
      indicated that HSP90 might be involved in regulation of hypoxia-driven
      proliferation.

PMID- 18726713
TI  - Genetic variability of the high-affinity IgE receptor alpha-subunit
      (FcepsilonRIalpha).
AB  - Our knowledge on the variability of FCER1A gene encoding for alpha-subunit of the
      high-affinity immunoglobulin E receptor (FcepsilonRI) that plays a central role
      in the pathogenesis of allergy and related disorders, has been recently much
      extended. Last findings from FCER1A mutational screening and genetic association
      studies, followed by functional analyses of the polymorphisms, are briefly
      summarized in this mini-review. The association between FCER1A gene variants and
      total serum IgE levels seems especially interesting and, supported by functional
      analyses of polymorphisms, may provide a rationale for pharmacogenetic studies on
      anti-IgE therapy that indirectly suppresses FcepsilonRI expression.

PMID- 18726716
TI  - [Carotid stenosis in octogenarians: operate or not operate].

PMID- 18726714
TI  - TCR-MHC docking orientation: natural selection, or thymic selection?
AB  - T cell receptors (TCR) dock on their peptide-major histocompatibility complex
      (pMHC) targets in a conserved orientation. Since amino acid sidechains are the
      foundation of specific protein-protein interactions, a simple explanation for the
      conserved docking orientation is that key amino acids encoded by the TCR and MHC
      genes have been selected and maintained through evolution in order to preserve
      TCR/pMHC binding. Expectations that follow from the hypothesis that TCR and MHC
      evolved to interact are discussed in light of the data that both support and
      refute them. Finally, an alternative and equally simple explanation for the
      driving force behind the conserved docking orientation is described.

PMID- 18726717
TI  - [Clinical outcome 6 years after autologous hematopoietic stem cell
      transplantation in multiple sclerosis].
AB  - INTRODUCTION: Autologous hematopoietic stem cell transplantation (AHSCT) remains
      as an experimental treatment for severe forms of multiple sclerosis (MS). We
      describe the clinical outcome of 14 patients included in a protocol of AHSCT
      after a median follow-up period of 6 years. METHODS: 14 patients (5 relapsing
      remitting and 9 secondary progressive) with a median number of relapses in the
      year before of 3 (1-7), Expanded Disability Status Scale (EDSS) of 6 (4.5-6.5)
      and decile of the multiple Sclerosis Severity Store (MSSS) 9 (7-10) were
      included. The procedure included carmustine, cyclophosphamide, antithymocyte
      globulin and T-cell depletion by CD34+ selection. RESULTS: The 4.5-year
      progression-free survival was 71%. The 6 year actuarial probability of
      progression-free survival was 62.5% and the disease activity-free survival of
      7.1%. The median EDSS was 6 (4-8.5) and the MSSS 8 (5-10). Only 2 patients
      presented enhanced T1 lesions. No long-term complications related to the
      procedure were observed. CONCLUSION: AHSCT cannot be deemed a curative treatment
      but may cause prolonged stabilisation or change the aggressive course of the
      disease.

PMID- 18726718
TI  - [Interobserver reliability among neurology resident physicians in the diagnosis
      of primary headaches according to the 2004].
AB  - INTRODUCTION: We determine the interobserver reliability among neurology resident
      physicians when diagnosing primary headaches using the 2004 International
      Headache Classification (IHC) compared to that obtained when compared with these
      observers and those of a consensus group (CG) made up of investigators and
      observers. PATIENTS AND METHODS: The study was performed in an adult and
      pediatric population from a 4th level Colombian hospital out-patient neurology
      clinic. After informed consent was obtained from each patient, a video was
      recorded, eliminating the facial images in order to prevent patient
      identification. Two same level residents (observer 1 and observer 2) with
      previous training in the international classification of headache disorders (IHD
      2) examined the video. Each video was examined separately with the classification
      in hand, making the diagnoses. The diagnoses obtained were compared between the
      observers and with the CG. RESULTS: We obtained a kappa index: 0.64 comparing
      residents, k: 0.66 comparing resident 1 to CG and kappa index 0.70 comparing
      resident 2 to CG in the level of groups. The kappa value obtained for the
      headache type level was 0.51 interobservers, 0.61 on comparing observer one with
      CG and 0.65 on comparing observer two with CG. CONCLUSION: Our results indicate
      that there is adequate reliability in the application of the 2004 IHC
      classification in the diagnosis of primary headaches among neurology resident
      physicians.

PMID- 18726715
TI  - Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis.
AB  - FoxP3(+)CD4(+)CD25(+) regulatory T (Treg) cells are implicated in a number of
      pathologic processes including elevated levels in cancers and infectious
      diseases, and reduced levels in autoimmune diseases. Treg cells are activated to
      modulate immune responses to avoid over-reactive immunity. However, conflicting
      findings are reported regarding relative levels of Treg cells during HIV-1
      infection and disease progression. The role of Treg cells in HIV-1 diseases
      (aberrant immune activation) is poorly understood due to lack of a robust model.
      We summarize here the regulation and function of Foxp3 in Treg cells and in
      modulating HIV-1 replication. Based on recent findings from SIV/monkey and
      HIV/humanized mouse models, a model of the dual role of Treg cells in HIV-1
      infection and immuno-pathogenesis is discussed.

PMID- 18726719
TI  - [Cost effectiveness analysis of the diagnosis of carpal tunnel syndrome using
      electrophysiological studies].
AB  - INTRODUCTION: The high demand for electrophysiological studies (EP studies) in
      paucisymptomatic patients with suspected carpal tunnel syndrome (CTS) creates
      overloads in neurological examination departments. Most of these requests in the
      referenced section of our hospital come from primary health care, however it also
      comes from other specialists. Many EP Studies for CTS are normal or have minimal
      alterations so that no change in the therapeutic attitude is required. Thus, it
      is not clear whether EP studies are cost-effective for suspected CTS without
      clinical evidence of axonal degeneration. METHODS: A decision-making and economic
      evaluation model was made to compare three strategies: option A (EP Studies for
      all patients with suspected CTS), option B (prior selection by neurologist and EP
      studies only if axonal CTS was suspected) and option C (prior selection by
      neurologist and EP studies only if CTS, axonal or otherwise was suspected). The
      study was conducted over a two month period on patients referred to the neurology
      department with suspected CTS. EP studies were considered to be the proof that
      established the final diagnosis. The consequences were determined in terms of
      correct diagnoses, cost and cost/effectiveness ratio for each strategy. A total
      number of 188 studies were performed, option C being the most cost-effective, but
      also the most expensive. CONCLUSIONS: When there is neurological screening, the
      cost-effectiveness ratio is better but it is also more expensive. It is
      recommended to favor option A with intermediate cost and an acceptable cost
      effectiveness ratio. However, this also generates great pressure on bud- 45 gets
      and care facilities which means that CTS diagnosis and criteria for referring
      patients to the neurological examination departments must be improved.

PMID- 18726720
TI  - [Hyperkalemic periodic paralysis: a Spanish family with the p.Thr704Met mutation
      in the SCN4A gene].
AB  - INTRODUCTION: Hyperkalemic periodic paralysis (HYPP) is an autosomal dominant
      disease characterized by recurrent episodes of muscular weakness with increased
      blood potassium levels. Here we present the clinical, analytical,
      neurophysiological and genetic findings of family with eight affected
      individuals, five of which were available for study. PATIENTS AND METHODS: The
      five patients were subjected to complete anamnesis, neurological examination,
      routine blood analysis and genetic study. Two of the patients were also examined
      both at the clinical and neurophysiological levels. In one case, the potassium
      levels were determined during a crisis. RESULTS: Almost all patients presented 2
      to 3 episodes of muscle weakness of the limbs per day of 30-45 min, and showed
      calf hypertrophy. During the observed episodes, the paralysis was massive in the
      lower limbs and the patients showed generalized osteotendinous areflexia. The
      potassium levels of the probandus measured during one of the episodes were
      elevated. The genetic analysis showed that all the affected individuals carried
      the p.Thr704Met mutation in the a subunit of the skeletal muscle sodium channel,
      encoded by the SCN4A gene. CONCLUSIONS: Our findings correlate well with those
      reported previously in HYPP, although the frequency of the episodes is
      exceptionally high in our family. HYPP is a channelopathy caused by mutations in
      the SCN4A gene, although molecular alterations have only been identified in 70 %
      of the patients. The affected members of the studied family bear a frequent
      mutation, p.Thr704Met, associated with a severe presentation of the disease.

PMID- 18726721
TI  - [Headache among oldest old (+75 years): findings from 736 consecutive subjects in
      outpatient neurological clinic].
AB  - INTRODUCTION: Although the elderly generally suffer less often from headache,
      many authors suggest that symptomatic headache and concomitant diseases could be
      more frequent. We performed a retrospective chart review of oldest old (+75
      years) patients who seek medical attention from headache. METHODS: A
      retrospective chart review (9 years) was carried on all oldest old subjects (> or
      =75 years) who were studied from outpatient neurological clinic. Headache
      diagnosis was made according to the new classification of the International
      Headache Society. RESULTS: Seven hundred and thirty six patients were reviewed.
      77,7% were females. Median age was 81,5 years (standard desviation: 5,3). This
      subjects were 1,7% from all consultations. 89,4% subjects suffered primary
      headaches. Tensional headache was the most frequent diagnosis. Serious causes
      were unusual. No patients had headache relationship with neoplasm or infections
      diseases. Only four subjects (0,6%) had temporal arteritis. Subjects with 81
      years and more had less migraine and more Arnold's neuralgia (Greater occipital
      neuralgia). CONCLUSIONS: In our study, headache among oldest old had relationship
      with benign causes like tensional headache. Although serious causes like neoplasm
      or infections disease were not detected in our patients, temporal arteritis could
      be an important cause to screen from outpatient neurological clinic.

PMID- 18726722
TI  - [Classic paraneoplastic syndromes: diagnostic and treatment approach].
AB  - INTRODUCTION: Paraneoplastic neurological syndromes are important complications
      of cancer that are usually immune mediated. According to the clinical and
      immunological features, two groups of disorders can be considered. One group
      includes disorders mediated by antibodies against cell surface neuronal antigens;
      these syndromes often respond to treatment and have a favorable outcome. The
      other group includes disorders associated with antibodies against intracellular
      antigens; these syndromes are likely mediated by T-cell mechanisms, respond
      poorly to treatment, and have a less favorable outcome. METHODS: Clinical and
      immunological analysis, and follow-up of four patients with classical
      paraneoplastic syndromes. RESULTS: Three patients had serum and CSF antibodies to
      intracellular antigens and one had no detectable antibodies. Despite the severity
      of the symptoms, prompt detection and treatment of the tumor and immunotherapy
      modified the course of the disease and resulted in substantial improvement of the
      quality of life. CONCLUSIONS: Prompt diagnosis of the tumor and immunotherapy may
      positively impact the clinical outcome and improve the quality of life of
      patients with paraneoplastic syndromes believed to have a poor prognosis.

PMID- 18726723
TI  - [If I were to wake up clumsy and shaking (10 years later)].
AB  - The diagnosis and treatment of early Parkinson's disease (PD) has undergone
      considerable changes in the last 10 years. Identification of genes responsible
      for familial forms of the disease as well as the possibility of detecting
      dopaminergic dysfunction before the appearance of motor symptoms has opened up
      the possibility of presymptomatic diagnosis. The concept of PD is changing.
      Therapeutic strategies are quite different. Several studies support the
      recommendation of not delaying the onset of dopaminergic therapies. Nonetheless,
      neuroprotection still has not been totally demonstrated and this continues to be
      an objective of priority.

PMID- 18726724
TI  - [Medullary cavernoma: radiological evolution with conservative treatment].

PMID- 18726725
TI  - [Posterior cerebral artery territory infarcts due to carotid dissection].
AB  - INTRODUCTION: About 20% of strokes in individuals under 45 years of age are due
      to cervicocephalic artery dissection. The magnetic resonance should be the first
      option in the diagnostic process when this etiology is suspected. Posterior fetal
      circulation is a variant in the embryogenic development that may cause posterior
      territory infarcts in carotid dissections or stenosis. CASE REPORT: We report the
      case of a 51 year-old male patient, with left occipitotemporal acute infarct and
      occlusion of the internal carotid and left posterior cerebral arteries as well as
      a probable carotid origin of the posterior cerebral artery. These findings were
      found in the duplex doppler sonography and were confirmed in the cranial magnetic
      resonance which also showed a dissection in the distal segment of the left
      internal carotid artery with a mural clot. CONCLUSIONS: Posterior territory
      strokes due to spontaneous carotid dissection are rare and there are few cases
      reported in the literature. We have reviewed the previous literature on this
      topic.

PMID- 18726726
TI  - [Third cranial nerve palsy due to intracranial hypotension syndrome].
AB  - INTRODUCTION: Intracranial hypotension syndrome (IHS) is clinically defined by
      orthostatic headache due to cerebrospinal fluid (CSF) hypovolemia. It is
      frequently associated with lower cranial nerve (CN) paresis, especially the 6th
      one. However, neuropathy of the 3rd CN is rare. CASE REPORT: A 43 year old man
      presented with orthostatic headache and vertical diplopia of gradual onset.
      Clinical examination detected incomplete, pupil sparing left third CN palsy.
      Magnetic resonance imaging (MRI) of the brain and spine demonstrated typical
      abnormalities that confirmed the clinical suspicion of IHS. Lumbar puncture
      showed an opening pressure of 5 cm of water. CSF disclosed mild protein elevation
      (0.63 g/l) and lymphocytic pleocytosis (13 cells/ml). A history of spinal trauma
      three months prior to the onset of the symptoms and lumbar fractures identified
      in a spine computed tomography scan suggested the likely origin of the CSF leak.
      The symptoms responded to conservative measures in three months and a cranial MRI
      performed ten months later was normal. DISCUSSION: Third CN palsy is an extremely
      unusual manifestation of IHS and contributes to the expansion of its clinical
      spectrum.

PMID- 18726727
TI  - [Congenital absence in the left frontal-temporal region without
      neuropsychological consequences].

PMID- 18726728
TI  - [Interferon-beta and autoinmune hepatitis in multiple sclerosis: cause-effect or
      association?].

PMID- 18726729
TI  - [Paraneoplastic dermatomyositis associated with prostate cancer].

PMID- 18726730
TI  - [Thalamic lacunar infarction with pure sensitive syndrome with atrial myxoma
      presentation].

PMID- 18726731
TI  - [Representation of the nummular healdache in general consultation in neurology].

PMID- 18726732
TI  - Detection of HLA-antibodies prior to renal transplantation: prospects and
      limitations of new assays.
AB  - Donor-specific HLA antibodies are responsible for most early renal allograft
      rejections and allograft losses. Therefore, detection of HLA antibodies prior to
      transplantation is an important step in the evaluation of renal allograft
      recipients. In this mini-review we will describe recent advances in the
      techniques used to detect donor-specific HLA antibodies with emphasis on their
      potential application for patient management and their current limitations.

PMID- 18726733
TI  - Psychological response and quality of life after transplantation: a comparison
      between heart, lung, liver and kidney recipients.
AB  - PRINCIPLES: Various non-specific questionnaires were used to measure quality of
      life and psychological wellbeing of patients after organ transplantation. At
      present cross-organ studies dealing specifically with the psychological response
      to a transplanted organ are non-existent in German-speaking countries. METHODS:
      The Transplant Effects Questionnaire TxEQ-D and the SF-36 Quality of Life
      Questionnaire were used to examine the psychological response and quality of life
      of 370 patients after heart, lung, liver or kidney transplantation. The organ
      groups were compared with regard to psychosocial parameters. RESULTS: 72% of
      patients develop a feeling of responsibility for the received organ and its
      function. This feeling is even stronger towards the patient's key relationships
      i.e. family, friends, the treatment team and the donor. 11.6% worry about the
      transplanted organ. Heart and lung patients report significantly fewer concerns
      than liver and kidney patients. Overall, only a minority of patients report
      feelings of guilt towards the donor (2.7%), problems in disclosing their
      transplant to others (2.4%), or difficulties in complying with medical orders
      (3.5%). Lung transplant patients show significantly better adherence.
      CONCLUSIONS: A feeling of responsibility towards those one is close to and
      towards the donor is a common psychological phenomenon after transplantation of
      an organ. Conscious feelings of guilt and shame are harboured by only a minority
      of patients. The fact that heart and lung patients worry less about their
      transplant might have primarily to do with the greater medical and psychosocial
      support in this group.

PMID- 18726734
TI  - Routine procedures in NICUs: factors influencing pain assessment and ranking by
      pain intensity.
AB  - BACKGROUND: Pain associated with routine procedures in NICUs is often
      inadequately managed. Barriers to more appropriate pain management are nurses'
      and physicians' knowledge and the challenges of collaborative decision-making.
      Few studies describe the differing perceptions of procedural pain intensity among
      nurses and physicians in NICUs which could complicate common decision-making.
      This study set out to explore the factors influencing pain intensity assessment
      and to gain insight into a possible pain intensity classification of routine
      procedures in the NICU. METHOD: A survey was conducted among 431 neonatal health
      care professionals from 4 tertiary level NICUs. Each routine procedure was
      assessed on a 10-point visual analogue scale (VAS) assuming absence of analgesia.
      RESULTS: Multiple ANCOVA models showed that nurses rated 19 of the 27 procedures
      as significantly more painful than did physicians (p<0.05). We found no
      differences in pain assessment based on professional experience, gender or age.
      Of the 27 procedures listed, 70% were rated as painful and 44% were judged very
      painful. Ranking and classification of the pain intensity of routine procedures
      were drawn up. The general ranking of the median across all procedures shows that
      "insertion of a thoracic drain" is assessed as the most painful procedure.
      CONCLUSIONS: The majority of routine procedures in an NICU are considered to be
      painful. Nurses generally rate procedures as more painful than do physicians.
      This difference in assessment deserves exploration in regard to its impact on
      collaborative decision-making in neonate pain management.

PMID- 18726735
TI  - Management of cryptorchidism in children: guidelines.
AB  - QUESTION: To develop clinical guidelines for the management of cryptorchidism in
      pre-pubertal boys, from early diagnosis through therapy to long-term follow-up
      and prognosis. METHOD: Systematic review of articles from the medical literature,
      referenced since 1966, using validated search strategies through the following
      databases: Medline, Cochrane Database of Systematic Reviews, Cochrane Register of
      Controlled Trials, EMBASE, DARE, ACP Journal Club, National Guidelines
      Clearinghouse, Guidelines International Network. Relevant articles published
      after 1988 were taken as the basis for the statements. Each statement was graded
      on the basis of the study design and on its methodological quality (GRADE
      approach). A multidisciplinary panel of local experts discussed and evaluated
      each statement on the strength of this evidence. RESULTS: 28 statements based on
      the best available evidence were drafted. The experts agreed with all but two
      statements, which were rated uncertain. CONCLUSIONS: Cryptorchidism is best
      diagnosed clinically, and treated by surgical orchiopexy at age 6-12 months,
      without a routine biopsy. If no testis is palpable, or if other signs of
      hypovirilisation such as hypospadias are present, the chromosomal sex and
      hormonal status must be assessed. Laparoscopy is the best way of diagnosing and
      managing intra-abdominal testes.

PMID- 18726736
TI  - Observed versus estimated IQ as an index of malingering in traumatic brain
      injury: classification accuracy in known groups.
AB  - This study examined the classification accuracy of observed WAIS-III VIQ, PIQ,
      and FSIQ minus Barona-estimate differential scores in the detection of Malingered
      Neurocognitive Dysfunction (MND) in Traumatic Brain Injury (TBI) using a known
      groups design. Two hundred eleven TBI patients were assigned to one of three
      groups: Not-MND (n = 87), Indeterminate (n = 68), and MND (n = 56). A General
      Clinical Sample of 93 no-incentive patients (e.g., CVA, memory disorder) was also
      included to better study specificity. The VIQ differential accurately
      differentiated MND from Not-MND TBI patients regardless of injury severity. The
      PIQ differential was only accurate in mild TBI and did not add incremental
      validity to the VIQ differential. This study indicates that VIQ declines of
      greater than 24 points are rare except in very severe TBI. Particularly in mild
      TBI, such differentials likely indicate intentional suppression of WAIS-III
      performance consistent with MND. Clinical application is discussed.

PMID- 18726737
TI  - Use of the binomial distribution to predict impairment: application in a
      nonclinical sample.
AB  - A mathematical model based on the binomial theory was developed to illustrate
      when abnormal score variations occur by chance in a multitest battery (Ingraham &
      Aiken, 1996). It has been successfully used as a comparison for obtained test
      scores in clinical samples, but not in nonclinical samples. In the current study,
      this model has been applied to demographically corrected scores on the Halstead
      Reitan Neuropsychological Test Battery, obtained from a sample of 94 nonclinical
      college students. Results found that 15% of the sample had impairments suggested
      by the Halstead Impairment Index, using criteria established by Reitan and
      Wolfson (1993). In addition, one-half of the sample obtained impaired scores on
      one or two tests. These results were compared to that predicted by the binomial
      model and found to be consistent. The model therefore serves as a useful resource
      for clinicians considering the probability of impaired test performance.

PMID- 18726738
TI  - Use of the Personality Assessment Inventory (PAI) in neuropsychological testing
      of psychiatric outpatients.
AB  - The relationship between clinical scales of the Personality Assessment Inventory
      (PAI) and neuropsychological test results was investigated in a sample of
      psychiatric outpatients. Bivariate correlations showed only the Somatic
      Complaints scale of the PAI to be related to the Memory subscales of the
      Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
      Better performance on Trails A was negatively related to the Somatic Complaints
      (SOM), Anxiety (ANX), Depression (DEP), and Borderline Features (BOR) scales of
      the PAI. No combination of PAI scales was related to neuropsychological test
      results, and no combination of PAI scales could discriminate upper- and lower
      scoring groups on RBANS Delayed Memory or RBANS Total Index scores. In addition,
      neuropsychological status was found to be independent of all but the SOM clinical
      scale of the PAI. The results of this study provide additional evidence that the
      PAI and neuropsychological measures provide unique and essentially nonoverlapping
      data.

PMID- 18726739
TI  - The relative importance of suboperations of prospective memory.
AB  - An event-based and a time-based prospective memory (PM) task, a script generation
      task, several working memory tasks, an incidental retrospective memory task, and
      a screen clock were implemented on the computer in one integrated procedure
      lasting between one and two hours. The procedure was designed to simulate four
      working days and four nights for a white-collar employee. Sixty-eight normal
      participants completed the task. Time-based prospective memory (self-injecting
      and going to bed at preordained times of day) shared unique variance with clock
      checking, but hardly at all with incidental retrospective memory. On the other
      hand, event-based prospective memory (answering a faint telephone cue as quickly
      as possible) shared unique variance with incidental retrospective memory of
      formally task irrelevant context and less with clock checking. The latter
      correlational dissociation of event-based versus time-based PM by retrospective
      memory reached significance, inspiring the idea that administrative versus
      clerical work might each impose its own type of PM demands. In both types of PM,
      low-level abilities (use of external aids and incidental encoding of context,
      respectively) seem to be critical for good performance, more so than for high
      order executive functions. Our software is offered to the readership to
      explicitate these findings further or for other research pursuits.

PMID- 18726740
TI  - Executive functions in a Turkish sample: associations with demographic variables
      and normative data.
AB  - Attention and executive functions are affected by demographic factors. The study
      presented in this paper examines the effects of education, gender, and age on the
      scores of the Color Trail Test (CTT) (D'Elia, Satz, Uchiyama, & White, 1999) and
      the Visual Verbal Test (VVT) (Feldman & Drasgow, 1959), which are considered to
      be measures of executive functions such as attention, cognitive flexibility, set
      shifting, abstraction, and concept formation. This paper also presents the
      normative data for 611 cognitively intact adult Turkish participants (male:female
      ratio = 361:250; age range = 20-100 years, mean age = 52.038; education range = 0
      25 years, mean education = 9.01). As expected, the effects of age and education
      were significant and sizeable, but the effect of gender was small. Results showed
      that the CTT and the VVT performances were lower for higher ages and lower
      educational levels. Based on these results, the current norms for both tests were
      stratified for age and education.

PMID- 18726741
TI  - Administration frequencies of WAIS-III supplementary and optional subtests of
      board-certified clinical neuropsychologists.
AB  - The present investigation surveyed board-certified clinical neuropsychologists in
      four geographic regions of the United States regarding their administration
      practices of the WAIS-III supplementary subtests (Letter-Number Sequencing,
      Symbol Search), optional subtest (Object Assembly), and optional procedures
      (Digit Symbol-Incidental Learning and Digit Symbol-Copy). Approximately 56% of
      the surveys were returned and usable. Regardless of geographic region, Letter
      Number Sequencing and Symbol Search were the most popular of the
      supplementary/optional components because they were administered more than 70% of
      the time. The Digit Symbol-Incidental Learning and Digit Symbol-Copy procedures
      were the second most frequently administered tasks. Object Assembly was the least
      frequently administered component by practitioners across the four geographic
      regions.

PMID- 18726742
TI  - Memory and executive functions in adolescents with posttreatment Lyme disease.
AB  - Although adults with late stage posttreatment Lyme disease often experience
      difficulties in memory, little is known about the relationship between cognition
      and Lyme disease in children and adolescents. Twenty-five adolescents with late
      stage posttreatment Lyme disease (symptoms > 6 months) and 25 participants
      without Lyme disease (matched on gender, IQ, age, socioeconomic status) were
      assessed for neuropsychological functioning, depression, school functioning, and
      predisease academic achievement. The Lyme group had significant deficits in
      cognition (short-term visual memory, short-term and delayed verbal memory, all
      forms of recognition memory), as well as worse attendance, grades, and subjective
      reports of memory problems, without differing in predisease achievement or
      depression. Deficits in visual memory exceeded deficits in verbal memory-a
      striking difference from what is reported in adults. These results reveal that
      adolescents with a history of treated Lyme disease are at risk for long-term
      problems in cognition and school functioning.

PMID- 18726743
TI  - The neurocognitive outcome of nocardia: a brief, longitudinal case study.
AB  - Nocardia infection is a rare bacterial disorder that tends to affect the lungs
      and, in immunocompromised individuals, may progress to the brain. The brief,
      consecutive neuropsychological and neurobehavioral data of a 49-year-old male who
      developed multiple nocardia-related brain abscesses in the left frontal,
      occipital, and right cerebellar areas are reviewed. Neuropsychological findings
      indicated that he maintained mild-to-moderate impairments, primarily in executive
      functions, upon follow-up evaluation 43 days subsequent to baseline evaluation.
      This case demonstrates the utility of brief, serial neuropsychological screening
      in tracking the progression of an infectious process for the purposes of
      treatment planning and disposition.

PMID- 18726745
TI  - The Computerized Test of Information Processing (CTIP) by Tom Tombaugh.

PMID- 18726746
TI  - Evaluation of a fully automated method to measure the critical removal stress of
      adult barnacles.
AB  - A computer-controlled force gauge designed to measure the adhesive strength of
      barnacles on test substrata is described. The instrument was evaluated with adult
      barnacles grown in situ on Silastic T2(R)-coated microscope slides and epoxy
      replicas adhered to the same substratum with synthetic adhesive. The force per
      unit area required to detach the barnacles (critical removal stress) using the
      new automated system was comparable to that obtained with ASTM D5618 (1994) (0.19
      and 0.28 MPa compared with 0.18 and 0.27 MPa for two batches of barnacles). The
      automated method showed a faster rate of force development compared with the
      manual spring force gauge used for ASTM D5618 (1994). The new instrument was as
      accurate and precise at determining surface area as manual delineation used with
      ASTM D5618 (1994). The method provided significant advantages such as higher
      throughput speed, the ability to test smaller barnacles (which took less time to
      grow) and to control the force application angle and speed. The variability in
      measurements was lower than previously reported, suggesting an improved ability
      to compare the results obtained by different researchers.

PMID- 18726747
TI  - Age differences in susceptibility to memory interference during recall of
      categorizable but not unrelated word lists.
AB  - The authors examined how divided attention (DA) and aging affect memory, and the
      use of organizational strategies, during retrieval. Younger and older adults
      studied a list of either unrelated or categorizable words presented auditorily
      under full attention, and later recalled them under full attention or DA
      condition with a word- or digit-monitoring distracting task. The magnitude of
      memory interference did not interact with age during retrieval of unrelated
      words. During retrieval of categorizable words, older adults suffered
      significantly greater memory interference than young in both DA conditions. The
      number of categories recalled was significantly reduced by the word- but not
      digit-based distracting task, and this effect did not differ across age groups.
      The number of words recalled per category was reduced in both DA conditions, in
      both age groups. Semantic clustering, corrected for total recall score, was
      reduced in older but not younger adults, in both DA conditions. Findings suggest
      that older adults cannot make use of strategies, to the same extent as do young,
      to boost memory for categorized words under DA conditions, leading to amplified
      memory interference.

PMID- 18726748
TI  - Are age differences in verbal learning related to interstimulus interval and
      education?
AB  - The present study investigated the effects of a narrow range of interstimulus
      intervals (ISI; 1, 2, or 3 s) on word-learning performance in relation to age and
      education. Individuals (N = 338) from four age groups (24 to 76 years) with low
      or high educational attainment were randomly assigned to one of three ISI
      conditions. Older age, lower education, and shorter ISI each led to lower
      performance. However, age differences in performance were not affected by ISI.
      Furthermore, lower educated individuals needed more time to achieve the same
      performance level as higher educated individuals.

PMID- 18726749
TI  - A reassessment of negative priming within the inhibition framework of cognitive
      aging: there is more in it than previously believed.
AB  - Three negative-priming studies were carried out to examine whether this paradigm
      allows a separation of the effects of aging on access, deletion, and restraint
      control of inhibition. In each study 24 younger (18 to 35 years old) and 24 older
      (57 to 82 years old) adults were asked to identify pictures. The results reveal
      difficulties among older adults in preventing the access of distracting
      perceptual input into responses; however, the ability to restrain inappropriate
      answers and the ability to delete once-relevant information are not affected by
      age.

PMID- 18726750
TI  - Aging and focus switching in working memory: excluding the potential role of
      memory load.
AB  - Disproportionate costs of switching focal attention within working memory have
      been put forward as an explanation for age-related performance impairment on the
      n-back task. The lag (n) in the n-back task is confounded by memory load,
      however. In the current study, it was attempted to tackle this issue by
      introducing a two-digit 1-back condition. This condition was intended to bridge
      the gap between the conventional 1-back and 2-back conditions by increasing
      memory load, but not n. Twenty young (mean age = 22 years) and 20 older adults
      (mean age = 65 years) were subjected to this adapted n-back paradigm. The results
      corroborated earlier results in that, relative to the young participants, the
      older participants were disproportionately impaired in the 2-back condition
      relative to both the conventional one-digit and the two-digit 1-back conditions.
      In line with previous research, this interaction was only found in the accuracy
      scores, not in the reaction times. It was concluded that disproportionate costs
      of focus switching rather than memory load explain age-related impairment on the
      n-back task.

PMID- 18726751
TI  - Do older adults show less confidence in their monitoring of learning?
AB  - Although aging has a minimal effect on the accuracy of people's judgments of
      learning (JOLs) at predicting future memory performance, older adults may be less
      confident in these memory judgments--similar to the age declines often reported
      with memory self-efficacy. To evaluate this possibility, the authors had younger
      and older adults make JOLs for paired associates and rate their confidence in the
      accuracy of each JOL. Age-related declines in confidence in judgments were
      evident for immediate JOLs but not for delayed JOLs. Implications of these
      outcomes for theory of JOLs and explaining age-related differences in self
      regulated study are discussed.

PMID- 18726752
TI  - Are there uniform age-related changes across tasks involving inhibitory control
      through access, deletion, and restraint functions? A preliminary investigation.
AB  - According to Hasher, Zacks, and May (Attention and performance XVII. Cognitive
      regulation of performance: Interaction of theory and application, pp. 653-675,
      MIT Press, 1999), a general age-related decline of inhibitory control affects the
      contents of working memory through three kinds of functions: limiting access to
      irrelevant information, deleting information that is no longer relevant, and
      restraining the production of dominant responses. Supportive evidence has been
      found in a wide variety of experimental tasks. In the present study, age-related
      changes were examined in the same group of 34 older (aged 60 to 82) and 30
      younger (aged 19 to 30) adults performing the same set of tasks involving the
      access, deletion, or restraint function. The results indicate that age-related
      declines in inhibition are not uniform but vary depending on task-specific
      characteristics.

PMID- 18726753
TI  - Modulatory role of glutathione monoester in augmenting age-associated neuronal
      antioxidant system.
AB  - An ever-increasing number of reports show the involvement of free radicals in the
      functional and structural changes occurring in the brain as a part of the normal
      aging process. This study aimed to assess the potential efficacy of glutathione
      monoester (GME) when administered intraperitoneally (12 mg/kg body weight) for 20
      days on memory and the antioxidant defense system and lipid peroxidation in
      discrete brain regions such as cortex, striatum, and hippocampus of young and
      aged rats. Age-associated decline in memory and activities of superoxide
      dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione,
      vitamin E, and vitamin C, and elevated levels of lipid peroxidation and oxidized
      glutathione, were observed in all the brain regions studied (p < .001). GME
      administration was effective in restoring the antioxidant status and in
      decreasing lipid peroxidation level in aged rat brain regions.

PMID- 18726754
TI  - Differential effects of normal aging on memory for odor-place and object-place
      associations.
AB  - Odor-place and object-place associative memory were compared in healthy older
      (over the age of 65) and young (18 to 25 years of age) adults. Twelve spatial
      locations were defined on a tabletop board. Either six odors or six objects were
      presented one at a time and each was paired with a location on the board. The
      participant then was presented with each stimulus individually and asked to place
      it in its paired location. Older adults showed impaired odor-place associative
      memory but unimpaired object-place memory compared to young adults. Item
      recognition memory for the individual stimuli or locations used on the
      associative memory task was similar in both groups. The results suggest that odor
      place associative memory is particularly affected by age-related brain changes.

PMID- 18726755
TI  - Age-related changes in tissue and plasma zinc levels: modulation by exogenously
      administered melatonin.
AB  - Melatonin (MEL) is synthesized mainly in the pineal gland and derived from 5
      hydroxytryptophan (5-HTP). Zinc (Zn) is one of the most important trace elements
      in the body. Zn and MEL levels are changed with aging. The aim of this study was
      to investigate the age-related changes of tissue and plasma Zn levels and effect
      of MEL administration on these parameters. Male wistar rats received for 3 weeks
      subcutaneous injection of MEL (10 mg/kg). Kidney and pancreas Zn levels in old
      rats were significantly lower than middle-aged group. Spleen, small intestine,
      and plasma Zn levels were not different in middle-aged and old rats. On the other
      hand, MEL treatment increased Zn levels of small intestine and plasma in middle
      aged rats. However, kidney, spleen, and pancreas Zn levels were unaffected by MEL
      treatment.

PMID- 18726756
TI  - Legal issues in accommodating the Americans with disabilities act to the diabetic
      worker.

PMID- 18726757
TI  - Mediation and medical malpractice: the need to understand why patients sue and a
      proposal for a specific model of mediation.

PMID- 18726758
TI  - Admissible expert testimony and summary judgment: reconciling Celotex and Daubert
      after Kochert.

PMID- 18726759
TI  - Genetic counseling: legal issues surrounding nondisclosure of paternity.

PMID- 18726760
TI  - National vaccine injury compensation program: the potential impact of Cedillo for
      vaccine-related autism cases.

PMID- 18726763
TI  - Analytical performance criteria. Field evaluation of diacetyl sampling and
      analytical methods.

PMID- 18726764
TI  - Experimental validation of a target method for balancing exhaust ventilation duct
      systems with dampers.
AB  - This study tested the "Target Method" for adjusting ventilation systems. The
      Target Method is based on target hood static pressures (SPh(target)) computed in
      a manner designed to take into account the estimated effects of dampers on the
      fan, the order of damper adjustments, and the ratio of the prebalancing branch
      airflows to their goals. It is aimed at achieving a desired relative distribution
      of airflows even if the fan output is far from ideal. The method assumes the fan
      output will be adjusted after the dampers are adjusted. The method is expected to
      produce lower fan pressure requirements than some commonly used methods. The
      method was tested on a working seven-branch, full-sized exhaust ventilation
      system in the West Virginia University Exposure Assessment Laboratory. Two
      radically different target distributions were tested with two replications
      apiece. Both target distributions of airflows were substantially different from
      the initial distribution, providing a high degree of challenge to the
      methodology. For each distribution, SPh(target) values were computed for the
      first round of adjustments. Each damper was adjusted until the observed value of
      the hood static pressure was nearly equal to that damper's computed SPh(target)
      value for that distribution. Each of the other branch dampers was adjusted
      similarly in turn. After the first round of adjustments, the median ratio of SPh
      to SPh(target) provided the targets for the partial second round of adjustments.
      Twenty-point Pitot traverses were used to determine the airflow in each branch
      duct both before and after employing the adjustment method, providing the basis
      to determine the success in reaching each of the two desired distributions. The
      percentage of excess airflow (assuming ideal adjustment of the fan speed) was
      below 2.2% for all experimental trials. An unpublished study by Vivek
      Balasubramanian showed that excess airflow was 4.8% to 8.5% in the same
      experimental system after two full rounds of adjustment using the customary
      Target Method. Under poor measurement conditions, the greater uncertainty of
      pressure measurements would likely produce somewhat higher excess airflows.

PMID- 18726765
TI  - Ask your doctor if this genetic test is right for you.

PMID- 18726766
TI  - Response to open peer commentaries on "Justifying a presumption of restraint in
      animal biotechnology research".

PMID- 18726767
TI  - An unprotected public.

PMID- 18726768
TI  - Like/as: metaphor and meaning in bioethics narrative.

PMID- 18726769
TI  - Direct to confusion: lessons learned from marketing BRCA testing.
AB  - Myriad Genetics holds a patent on testing for the hereditary breast and ovarian
      cancer genes, BRCA1 and BRCA2, and therefore has a forced monopoly on this
      critical genetic test. Myriad launched a Direct-to-Consumer (DTC) marketing
      campaign in the Northeast United States in September 2007 and plans to expand
      that campaign to Florida and Texas in 2008. The ethics of Myriad's patent, forced
      monopoly and DTC campaign will be reviewed, as well as the impact of this
      situation on patient access and care, physician liability, and the future of DTC
      campaigns for genetic testing.

PMID- 18726770
TI  - Why John Stuart Mill would support restriction on DTC marketing of genetic tests.

PMID- 18726771
TI  - DTC marketing of genetic tests: the perfect storm.

PMID- 18726772
TI  - Genetic testing for vulnerable populations: what kinds of communication we need
      and do not need.

PMID- 18726773
TI  - DTC genetic services: a look across the pond.

PMID- 18726774
TI  - Consumer alert: ethical issues raised by the sale of genetic tests directly to
      consumers.

PMID- 18726775
TI  - Using lessons learned from BRCA testing and marketing: what lies ahead for whole
      genome scanning services.

PMID- 18726776
TI  - Waiting to be born: the ethical implications of the generation of "NUBorn" and
      "NUAge" mice from pre-pubertal ovarian tissue.
AB  - Oncofertility is one of the 9 NIH Roadmap Initiatives, federal grants intended to
      explore previously intractable questions, and it describes a new field that
      exists in the liminal space between cancer treatment and its sequelae, IVF
      clinics and their yearning, and basic research in cell growth, biomaterials, and
      reproductive science and its tempting promises. Cancer diagnoses, which were once
      thought universally fatal, now often entail management of a chronic disease. Yet
      the therapies are rigorous, must start immediately, and in many cases result in
      premature failure of the body's reproductive ability. In women, this loss is
      especially poignant; unlike the routine storage of sperm, which is done in men
      and boys facing similar treatment decisions, freezing oocytes in anticipation of
      fertility loss is not possible in most cases, and creating an embryo within days
      of diagnosis raises significant moral, social and medical challenges.
      Oncofertility is the study of how to harvest ovarian tissue in women facing
      cancer to preserve their gametes for future use with IVF, thus allowing the
      decisions about childbearing to be deferred and reproductive choices to be
      preserved. The research endeavor uses the capacity of the ovarian follicle to
      produce eggs in vitro. Developing the human follicle to ovulate successfully
      outside the body is scientifically difficult and ethically challenging.
      Infertility is linked to long-standing religious and moral traditions, and is
      intertwined with deeply contentious social narratives about women, families,
      illness and birth. Is the research morally permissible? Perhaps imperative if
      understood as a repair from iatrogenic harms? How are considerations of justice
      central to the work? How will vulnerable subjects be protected? What are the
      moral implications of the work for women, children and families? What are the
      implications for society if women could store ovarian tissue as a way of stopping
      the biological clock? What are the moral possibilities and challenges if eggs can
      be produced in large quantities from a stored ovarian tissue?

PMID- 18726777
TI  - Some perils of "waiting to be born": fertility preservation in girls facing
      certain treatments for cancer.

PMID- 18726778
TI  - Freezing eggs for lifestyle reasons.

PMID- 18726779
TI  - Justifying a presumption of restraint in animal biotechnology research.
AB  - Articulating the public's widespread unease about animal biotechnology has not
      been easy, and the first attempts have not been able to provide an effective tool
      for navigating the moral permissibility of this research. Because these moral
      intuitions have been difficult to cash out, they have been belittled as
      representing nothing more than fear or confusion. But there are sound
      philosophical reasons supporting the public's opposition to animal biotechnology
      and these arguments justify a default position of resistance I call the
      Presumption of Restraint. The Presumption of Restraint constitutes a
      justificatory process that sets out the criteria for permitting or rejecting
      individual biotechnology projects. This Presumption of Restraint can be
      overridden by compelling arguments that speak to a project's moral and scientific
      merit. This strategy creates a middle-of-the-road stance that can embrace
      particular projects, while rejecting others. The Presumption of Restraint can
      also serve as a model for assessing moral permissibility in other areas of
      technological innovation.

PMID- 18726780
TI  - Exercising restraint in the creation of animal-human chimeras.

PMID- 18726781
TI  - Animal biotechnology and the non-identity problem.

PMID- 18726782
TI  - Animal biotechnology: how not to presume.

PMID- 18726783
TI  - Toward a zoocentric animal ethics.

PMID- 18726784
TI  - Open to debate: moral consideration and the lab monkey.

PMID- 18726787
TI  - Metabolic effects of the obstructive sleep apnea syndrome and cardiovascular
      risk.
AB  - The obstructive sleep apnea syndrome (OSAS) is characterized by collapse of the
      upper airway during sleep, recurring apneas, intermittent hypoxemia and daytime
      somnolence. OSAS is often associated with obesity, and its prevalence is expected
      to rise due to the obesity epidemics worldwide. OSAS is associated with increased
      cardiovascular risk which appears to be normalized by treatment with nasal
      continuous positive airway pressure (nCPAP) during sleep, suggesting an
      independent role of OSAS in accelerating atherosclerosis. Insulin resistance (IR)
      and the metabolic syndrome (MetS) are often found in OSAS patients, but the
      relative role played by OSAS and obesity is still unclear. Both OSAS and MetS may
      exert negative synergistic effects on the cardiovascular system through multiple
      mechanisms (hypoxemia, sleep disruption, activation of the sympathetic nervous
      system, inflammatory activation). Besides nCPAP treatment, pharmacologic
      interventions to treat obesity and the MetS could improve cardiovascular
      prevention in OSAS.

PMID- 18726788
TI  - Action-dependent plasticity in peripersonal space representations.
AB  - The space immediately around the body is represented by multisensory integrative
      processes implemented in frontal and parietal lobes. This network has basically a
      motor function-that is, planning an approaching or defensive motor response to
      stimuli presented close to the body. Peripersonal space representations are
      highly plastic as a function of experience. Indeed, using a tool to act in far
      space can drive an elongation of peripersonal space representation towards the
      acting space. In this review functional and dynamic properties of such plasticity
      are reviewed in light of recent experimental findings from our own group and
      other laboratories.

PMID- 18726789
TI  - Review of the toxicology of chlorpyrifos with an emphasis on human exposure and
      neurodevelopment.
AB  - This review examines the large body of toxicological and epidemiological
      information on human exposures to chlorpyrifos, with an emphasis on the
      controversial potential for chlorpyrifos to induce neurodevelopmental effects at
      low doses. The results of this review demonstrate that the use of urinary 3,5,6
      trichlorpyridinol (TCPy), a metabolite of chlorpyrifos as a biomarker of
      nonoccupational exposure is problematic and may overestimate nonoccupational
      exposures to chlorpyrifos by 10-to 20-fold because of the widespread presence of
      both TCPy and chlorpyrifos-methyl in the food supply. Current "background"
      (nonoccupational) levels of exposure to chlorpyrifos are several orders of
      magnitude lower than those required to inhibit plasma cholinesterase activity,
      which is a more sensitive target than nervous system cholinesterase. However,
      several in vitro studies have identified putative neurodevelopmental mechanisms
      that are altered at concentrations of chlorpyrifos below those that inhibit
      cholinesterases. Although one human cohort study reported an association between
      maternal and cord blood chlorpyrifos levels and several measures of
      neurodevelopment, two other cohort studies that utilized urinary TCPy as a
      surrogate for chlorpyrifos exposure did not demonstrate an association. Although
      the weight of the scientific evidence demonstrates that current levels of
      chlorpyrifos exposure will not have any adverse effects on neurodevelopment that
      might result from inhibition of nervous system cholinesterases, several recent
      studies propose alternative mechanisms. Thus, further in vivo investigation on
      neurodevelopment in an appropriate animal model is needed; additional
      epidemiological studies may be warranted if a suitable, chlorpyrifos-exposed
      cohort can be identified and more rigorous measures of exposure are utilized.

PMID- 18726792
TI  - "We wanted a birth experience, not a medical experience": exploring Canadian
      women's use of midwifery.
AB  - In this study I explore Canadian women's use of midwifery to examine whether
      their choice represents a resistance to the medicalization of
      pregnancy/childbirth. Through my analysis of the data I identified eight ways the
      women's deliberate decision to pursue midwifery care represented resistance to
      medicalization. In so doing, I demonstrate how women actively assert their agency
      over reproduction thus shaping their own reproductive health experiences. The
      outcome of their resistance and resultant use of midwifery was empowerment.
      Theoretically the research contributes to understanding the intentionality of
      resistance and a continuum of resistant behavior.

PMID- 18726793
TI  - Determinants of infant-feeding choice among young women in Hilo, Hawaii.
AB  - Our multicultural island community is unique in that many young mothers live in
      multigenerational households. In this qualitative study, we examined the factors
      that influenced young mothers' infant-feeding practices in Hilo, a small rural
      town in the Hawaiian Islands. The study participants consisted of young mothers,
      health care professionals, and educators. Our findings suggest that both the
      young mother's mother and her partner are very influential in the infant-feeding
      decision. Many young women in our study bottle fed to obtain assistance in
      caretaking, and to facilitate public breastfeeding. Additionally, we explored
      young mother's views of sexuality and breastfeeding, and their health promotion
      implications.

PMID- 18726794
TI  - The social and environmental factors underlying maternal malnutrition in rural
      Bangladesh: implications for reproductive health and nutrition programs.
AB  - Levels of low birth weight (LBW) and maternal malnutrition in rural Bangladesh
      are among the highest in the world. We surveyed dietary practices among pregnant
      mothers in a rural area served by a reproductive health and nutrition program. In
      total, 30 semi-structured interviews and five focus group discussions were
      carried out, supplemented by participant observations. Despite high levels of
      awareness of nutritional dietary requirements, half the women reported unchanged
      or reduced food intake during pregnancy. Dietary taboos and food aversions were
      widely practiced. Women consistently received the last and smallest food shares
      during mealtimes. The findings highlight the need to address traditional dietary
      taboos and preferenaces, and actively target key household decisionmakers,
      namely, husbands and mothers-in-law, in nutrition behavior change communication.

PMID- 18726795
TI  - Understanding maternal breastfeeding confidence: a Gadamerian hermeneutic
      analysis of women's stories.
AB  - Our aim in this Gadamerian hermeneutic study was to understand maternal
      breastfeeding confidence and its meaning through listening to women's voices
      describing their experiences within the context of the United States. We asked 13
      women, aged 23 to 42 years, who had breastfed a child within the last 2 years to
      tell us their breastfeeding stories. Women experienced maternal breastfeeding
      confidence as a dynamic interaction between their expectations, their infant(')s
      breastfeeding behavior, and sources of support. They described experiences that
      enhanced or diminished their confidence. Health professionals can use these
      findings to plan approaches that promote and support maternal breastfeeding
      confidence.

PMID- 18726796
TI  - Accessing maternity care in rural Canada: there's more to the story than distance
      to a doctor.
AB  - Drawing upon a comparative, qualitative study of the experiences of rural women
      accessing maternity care in two Canadian provinces, we demonstrate that
      availability of services, having economic and informational resources to access
      the services offered, and the appropriateness of those services in terms of
      gender, continuity of care, confidentiality, quality of care, and cultural fit
      are key to an accurate understanding of health care access. We explore the
      implications of living rurally on each of these dimensions, thereby revealing
      both gaps in and solutions to rural maternity care access that narrower,
      proximity-based definitions miss.

PMID- 18726797
TI  - Factors affecting women's health-related behaviors and safe motherhood: a
      qualitative study from a refugee camp in eastern Sudan.
AB  - We aim to provide a deeper understanding of a broader range of potential factors
      affecting risk behaviors related to safe motherhood among refugee women in
      Eastern Sudan, thus creating a basis for further research in behavioral change.
      Risk behaviors chosen for this study follow (1) practice of female genital
      cutting, (2) adopting family planning (FP) practices, (3) usage of a skilled
      birth attendant, and (4) response to obstetric complications. Analyzing findings
      with the PRECEDE-PROCEED model, we found that factors frequently were
      uncontrollable for an individual woman, suggesting the importance of a supportive
      political, social, and educational environment for safe motherhood.

PMID- 18726798
TI  - The role of mothers in household health-seeking behavior and decision-making in
      childhood febrile illness in Okurikang/Ikot Effiong Otop community, Cross River
      State, Nigeria.
AB  - The authors examine mothers and decision making during childhood febrile illness
      in rural Nigeria in this article. Employing a cross-sectional descriptive
      community survey, we elicited information from four categories of caregivers with
      the help of structured questionnaires. Apart from sociostructural economic
      factors, the authors reveal how interlocking objectives and values as expressed
      in extended family institutions functioned to influence both behavior and
      decision making of mothers. We suggest expanding the target of health education
      in the rural areas to include the family as an extended structure.

PMID- 18726799
TI  - The patient's perception of having recovered from an eating disorder.
AB  - Our aim in this study was to describe how patients perceive having recovered from
      eating disorders. A qualitative method with a phenomenographic approach was used
      to identify various ways of experiencing recovery. Four categories emerged,
      describing how the subjects now relate in a relaxed and accepting manner to food,
      the body, themselves as individuals, and their social environment. Some perceived
      recovery as coping with emotions, while others experienced themselves as
      healthier than people in general regarding food and weight. Different aspects
      were emphasized as important for recovery. As long as patients perceive
      themselves as recovered, it is not necessary that they fulfill all conceivable
      criteria for recovery.

PMID- 18726800
TI  - Women's social position and health-seeking behaviors: is the health care system
      accessible and responsive in Pakistan?
AB  - To make the health care system more accessible and responsive to women
      particularly in developing countries, it is imperative to study the health
      seeking behaviors and factors determining utilization of health care services.
      This study was carried out in close collaboration with Aga Khan Health Services,
      Pakistan (AKHSP) and the Health Department of Northern Areas of Pakistan. Key
      findings indicate that more than one-third of women did not know the cause of
      their reported illness. There is a median delay of 3 days before a consultation.
      Local women utilize AKHSP services far more than other health services due to the
      quality of services offered and the availability of female health staff. The
      perception of receiving the required treatment is lowest for government health
      services. Consulting faith healers is a common practice. Health education and
      health promotion campaigns are needed to change existing health-seeking behaviors
      among women. Social arrangements should be thoughtfully considered to make the
      health system more responsive. More female staff needs to be deployed in
      government health facilities. A public-private partnership seems to provide a
      means to strengthen the health care system and consequently to promote women's
      health.

PMID- 18726802
TI  - The contributions of Ramon y Cajal and other Spanish authors to hypnosis.
AB  - The authors review the most important Spanish contributions to hypnosis during
      the 19th and 20th centuries, with emphasis on the work of Santiago Ramon y Cajal,
      winner of the 1906 Nobel Prize in medicine. It is widely accepted that he
      provided a basic foundation for modern neurosciences with his work on neuronal
      staining and synaptic transmission. What is missing in most accounts of his work
      is his longstanding interest and work on hypnosis and anomalous phenomena. This
      article summarizes that lost legacy, discusses other Spanish hypnosis pioneers
      and gives a brief overview of current hypnosis activities in Spain.

PMID- 18726803
TI  - Paradoxical hypnotic experiences in escaping constraining dilemmas: a clinical
      example.
AB  - Deciding how to choose from opposing options often seriously impacts people's
      final selections. Such constraining options are frequently associated with
      feelings of hopelessness, depression, or chronic pain. As an example of such
      situations, a model is presented with material from a single case that utilized
      previous contradictory experiences in the treatment of a woman patient who
      suffers from chronic pelvic pain. The case summarizes how previous experiences,
      which have been paradoxical, can serve as substrates of behavioral change, which
      in turn can emerge in a way that allows the patient to integrate these
      experiences, personally and slowly, without conscious effort.

PMID- 18726804
TI  - Israeli norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A.
AB  - A Hebrew version of the Harvard Group Scale of Hypnotic Susceptibility, Form A
      (HGSHS:A) was administered to 283 subjects. Results were compared with those
      obtained for the English original administered in the United States, Canada, and
      Australia, as well as with versions translated into Swedish, Romanian, Italian,
      Finnish, Danish, Spanish, and German. Mean scores were similar to the Canadian
      and Australian, though lower than the others. No differences were found between
      males and females. Pass rates for individual items were similar or lower than
      elsewhere. Item reliability was similar to the other non-English versions. The
      author speculates that the slightly lower scores obtained may be due to the
      larger group of subjects present in each session. Overall, the Israeli data are
      congruent with the reference samples.

PMID- 18726805
TI  - The hypnotist in the hypnosis interaction: the impact of first impressions on
      perceptions of hypnotizability.
AB  - Hypnotist perceptions of participant cues and behaviors were investigated in an
      in-depth phenomenological study focusing on the influence of participant
      hypnotizability and hypnotist style. Two hypnotists and 124 participants (63
      hypnotizable and 61 nonhypnotizable) took part. Two modifications of the
      Experiential Analysis Technique (EAT) were employed. One version involved a new
      modification where both hypnotist and participant took part together in the EAT
      session. The second version involved the EAT with the hypnotist alone as per an
      existing modification of the technique. Results extend earlier work pointing to
      the active, sentient nature of hypnotist involvement and highlight the particular
      importance of first impressions in shaping hypnotists' perceptions of participant
      hypnotizability. Results point to difficulties inherent in the hypnotist role.
      Findings overall support devoting increased attention to the nature of
      hypnotists' involvement and its implications for understanding relational
      processes in hypnosis.

PMID- 18726806
TI  - Deja vu in the laboratory: a behavioral and experiential comparison of
      posthypnotic amnesia and posthypnotic familiarity.
AB  - This experiment aimed to create a laboratory analogue of deja vu. During
      hypnosis, 1 group of high hypnotizables completed a puzzle game and then received
      a posthypnotic amnesia suggestion to forget the game (PHA condition). Another
      group of highs were not given the game but received a posthypnotic familiarity
      suggestion that it would feel familiar (PHF condition). After hypnosis, all
      participants were given the game and described their reactions to it. Whereas 83%
      of participants in both conditions passed their respective suggestions, more in
      the PHF condition felt a sense of deja vu. An EAT inquiry revealed that they
      experienced sensory fascination and confusion about the source of familiarity,
      akin to everyday deja vu. These findings highlight the value of using hypnosis as
      a laboratory analogue of deja vu and provide a framework for investigating
      clinical manifestations of this phenomenon.

PMID- 18726807
TI  - Virtual reality hypnosis in the treatment of chronic neuropathic pain: a case
      report.
AB  - This case report evaluates virtual reality hypnosis (VRH) in treating chronic
      neuropathic pain in a patient with a 5-year history of failed treatments. The
      patient participated in a 6-month trial of VRH, and her pain ratings of intensity
      and unpleasantness dropped on average 36% and 33%, respectively, over the course
      of 33 sessions. In addition, she reported both no pain and a reduction of pain
      for an average of 3.86 and 12.21 hours, respectively, after treatment sessions
      throughout the course of the VRH treatment. These reductions and the duration of
      treatment effects following VRH treatment were superior to those following a
      trial of standard hypnosis (non-VR) treatment. However, the pain reductions with
      VRH did not persist over long periods of time. The findings support the potential
      of VRH treatment for helping individuals with refractory chronic pain conditions.

PMID- 18726808
TI  - Neurophysiological attributes of the hypnotic state and the utility of hypnosis
      in pediatric medicine and burn care.
AB  - Three articles of special interest to the hypnosis community recently appeared in
      the general scientific and medical literatures. The first paper is a thoughtful
      review of the clinical applications of hypnosis in pediatric settings. The second
      article reports the findings of a randomized, controlled trial of hypnosis for
      burn-wound care, carried out at the University of Washington Medical School. The
      third article describes an innovative EEG laboratory case study tracking the
      cortex functional connectivity of a highly hypnotizable subject across various
      baseline and experimental conditions. These three articles are sturdy examples of
      how hypnosis illuminates (and is illuminated by) medical and psychological
      science.

PMID- 18726809
TI  - Values and health: tough challenges lie ahead.

PMID- 18726811
TI  - Applying the common sense model to measure representations of arsenic
      contaminated well water.
AB  - Theory-based research is needed to understand how people respond to environmental
      health risk information. Both the common sense model (CSM) of self-regulation and
      the mental models approach propose that information shapes individuals' personal
      understandings that, in turn, influence their decisions and actions. We compare
      these frameworks and explain how the CSM was applied to describe and measure
      mental representations of arsenic contaminated well water. Educational
      information, key informant interviews, and environmental risk literature were
      used to develop survey items to measure dimensions of cognitive representations
      (identity, cause, timeline, consequences, control) and emotional representations.
      Surveys mailed to 1,067 private well users with moderate and elevated arsenic
      levels yielded an 84 % response rate (n = 897). Exploratory and confirmatory
      factor analyses of data from the elevated arsenic group identified a factor
      structure that retained the CSM representational structure and was consistent
      across moderate and elevated arsenic groups. The CSM has utility for describing
      and measuring representations of environmental health risks, thus supporting its
      application to environmental health risk communication research.

PMID- 18726810
TI  - News coverage of cancer in the United States: a national sample of newspapers,
      television, and magazines.
AB  - A content analysis of cancer news coverage in a sample of local and national
      newspapers, television, and magazines was conducted for the years 2002 and 2003.
      Analyses compared proportions of mentions of cancer sites with proportional
      contribution to cancer incidence and mortality based on available epidemiological
      estimates. Analyses also examined relative attention provided to prevention,
      detection, treatment, causes, and outcomes of various cancers. Results indicated
      that coverage reflected incidence rates more closely than they did mortality
      rates, but in both cases coverage under-represented the contribution of lung
      cancer to morbidity and mortality and over-represented the contribution of breast
      cancer. Of greater public health concern was the limited coverage of prevention
      and detection even for highly preventable or relatively easily detected cancers.
      Implications of findings are discussed.

PMID- 18726812
TI  - MyStudentBody-Stress: an online stress management intervention for college
      students.
AB  - College students who have high stress levels tend to experience an increased risk
      of academic difficulties, substance abuse, and emotional problems. To enhance
      student stress management and health promoting behaviors, an online stress
      management intervention called MyStudentBody-Stress (MyStudentBody-Stress) was
      developed and tested. College students at six U.S. colleges were randomized to
      one of three conditions: MyStudentBody-Stress, a control health information
      website, or no intervention. The differences between groups on stress control and
      health behavior measures were compared at baseline, and at 1, 3, and 6 months
      after baseline. Although there were no between-group differences on primary
      outcome variables, secondary analyses indicated that MyStudentBody-Stress
      participants were more likely to increase weekly physical activity, use specific
      stress management methods, and exhibit decreased anxiety and family problems.
      These findings indicate some potentially beneficial effects of online stress
      management programming for college students. Implications for college health
      practitioners are discussed.

PMID- 18726813
TI  - Physicians who do and do not recommend children get all vaccinations.
AB  - The objectives of this study were to determine (1) the proportion of physicians
      who do and do not recommend that children receive all available vaccines and (2)
      physician characteristics, attitudes, and behaviors associated with not
      recommending children receive all vaccines. A self-administered, cross-sectional
      electronic survey of physicians was conducted in 2005. Analyses were restricted
      to pediatricians (n = 250) and family practitioners (n = 484) who indicated they
      see at least five pediatric patients per week. A total of 1,935 surveys were
      distributed, and 1,251 (65%) physicians responded. Eleven percent of the
      physicians included in the analysis did not recommend to parents that children
      receive all available vaccines. Compared with physicians who recommended all
      vaccines for children, physicians who did not were more likely to be family
      practitioners versus pediatricians (OR = 2.9, CI = 1.4-5.8), agree or be neutral
      versus disagree that they have some concerns about childhood immunization safety
      (OR = 3.1, CI = 1.8-5.2), and have <or= 3 versus >or= 8 physicians in their
      practice (OR = 2.0, CI = 1.1-3.7). We conclude that physician characteristics and
      concerns about childhood immunizations are associated with not recommending all
      childhood vaccines. Further investigation of physicians' concerns about vaccine
      safety is needed to improve health communications directed toward health care
      providers.

PMID- 18726814
TI  - Perspective: the role of numeracy in health care.
AB  - Numeracy, the "ability to understand and use numbers in daily life" is an
      important but understudied component of literacy. Numeracy-related tasks are
      common in health care and include understanding nutrition information,
      interpreting blood sugar readings and other clinical data, adjusting medications,
      and understanding probability in risk communication. While literacy and numeracy
      are strongly correlated, we have identified many patients with adequate reading
      ability but poor numeracy skills. Better tools to measure numeracy and more
      studies to assess the unique contribution of numeracy are needed. This research
      can contribute to developing interventions to improve outcomes for patients with
      poor numeracy.

PMID- 18726815
TI  - Can movie theater advertisements promote health behaviors? Evaluation of a flu
      vaccination pilot campaign.
AB  - As part of a multimedia campaign to promote annual influenza vaccination, three
      slides were shown as part of the slide show of advertisements prior to the
      beginning of previews in movie theaters in San Diego County. Intercept surveys
      were conducted following the movie. The primary target groups for the campaign
      were adults with children 6 months to 2 years of age and adults over 50 years of
      age. Overall, 88% of exposed patrons reported seeing some type of movie ad. Among
      those who recalled any ad, 24% recalled the flu advertisement. In contrast,
      recall of flu-related news coverage was high, with over 95% of exposed and
      comparison interviewees recalling news stories during the campaign period. While
      56% of those interviewed remembered one or more specific flu-related news items,
      individuals within this group who also had also been exposed to the movie ads
      were not more likely to recall flu campaign advertisements. We describe a method
      for estimating valid recalls and cost per valid exposure. Further research that
      compares movie ads with public service announcements (PSAs) in other venues is
      necessary to solidify our conclusions that movie advertising is a highly cost
      effective medium for health communication.

PMID- 18726817
TI  - Development of a liposome formulation for D-cycloserine local delivery.
AB  - Multilamellar liposomes loaded with D-cycloserine (D-CS) were prepared by a thin
      layer evaporation technique, followed by freezing and thawing cycles. Charged
      components and bioadhesive material, such as distearolylphosphatitylethanolamine
      covalently coupled with methoxypolyethyleneglycol, were used to prepare liposomes
      with different physico-chemical and technological properties. Negatively charged
      liposomes showed higher D-CS encapsulation efficiency (about 37%, w/w) than
      neutral and positively charged liposomes (about 5 and 17%, w/w, respectively).
      All formulations showed in vitro, after a burst effect, a prolonged release of
      the encapsulated drug. Lipid vesicles made of dipalmitoylphosphatidylcholine
      (DPPC) were used as a biomembrane model to evaluate in vitro the interaction of D
      CS with biological membranes. Differential scanning calorimetry was used as a
      simple and noninvasive technique of analysis. D-CS was distributed in the aqueous
      compartments of liposomes for interaction with the phospholipid polar head-groups
      (enhancement of Delta H value). However, due to its high diffusibility the drug
      was also able to freely permeate through DPPC liposomes, altering during this
      passage the hydrophobic domains of the bilayers. Stability studies were performed
      at different temperatures and pH values to assay the integrity of the drug during
      the liposome production steps. D-CS was rapidly degraded at acidic pH, but no
      significant hydrolysis was observed at pH 7.4 after 7 days.

PMID- 18726818
TI  - Preparation of aminoglycoside-loaded chitosan nanoparticles using dextran
      sulphate as a counterion.
AB  - PURPOSE: To prepare aminoglycoside (AG) (streptomycin, gentamicin and tobramycin)
      loaded chitosan nanoparticles with high drug incorporation efficiency and test
      the in vivo oral efficacy of streptomycin (SM) loaded chitosan nanoparticles in a
      Mycobacterium tuberculosis (TB) chronic infection mouse model. METHOD: Dextran
      sulphate (a polyanion) was used to shield the positive charge of AG and increase
      the drug incorporation in the chitosan nanoparticle. By varying the concentration
      of each component, the formulation of SM-loaded chitosan nanoparticle was
      optimized by monitoring the drug incorporation efficacy and particle size. The
      mechanism of the nanoparticle formation was suggested and the preparation method
      was applied to two other aminoglycosides (AG): gentamicin (GM) and tobramycin
      (TM). The resulting nanoparticles were characterized by particle diameter, drug
      incorporation efficacy, drug loading efficacy and zeta potential. The in vitro
      drug release from these nanoparticles was carried out in pH 1.2 and pH 7.4
      buffer. Preliminary in vivo oral efficacy studies of SM-loaded chitosan
      nanoparticles was performed in a Mycobacterium tuberculosis (TB) chronic
      infection mouse model. RESULTS: The optimal concentration of streptomycin
      (SM)/dextran sulphate/chitosan/tripolyphosphate (TPP) for SM nanoparticles
      preparation was 2/1.2/2/0.8 mg mL(-1). Through calculation, the optimal
      concentrations of dextran sulphate are 2.5 mg mL(-1) and 2.4 mg mL(-1) for 2 mg
      mL(-1) gentamicin and tobramycin, respectively (Table 1). The resulting AG
      chitosan nanoparticles had a high drug incorporation efficacy with particle sizes
      in the nanometre range. The in vitro drug release studies showed that more than
      60% drug is retained inside the nanoparticles in pH 1.2 buffer after 6 h. The
      preliminary in vivo results indicated that oral SM chitosan nanoparticles induced
      one log 10 reduction (p < 0.01) in growth of the bacilli and were as effective as
      subcutaneously injected aqueous SM solution at the same concentration (100 mg kg(
      1)). CONCLUSION: Dextran sulphate can significantly increase AG incorporation
      into the chitosan nanoparticles. The concentration of each component was critical
      in preparing AG-loaded chitosan nanoparticles. The chitosan nanoparticles
      designed in this study may provide a promising oral drug delivery formulation for
      AG which usually, in tuberculosis treatment, is administrated as an injectible
      preparation.

PMID- 18726819
TI  - Evaluation of the effect of media velocity on filter efficiency and most
      penetrating particle size of nuclear grade high-efficiency particulate air
      filters.
AB  - High-efficiency particulate air (HEPA) filters are widely used to control
      particulate matter emissions from processes that involve management or treatment
      of radioactive materials. Section FC of the American Society of Mechanical
      Engineers AG-1 Code on Nuclear Air and Gas Treatment currently restricts media
      velocity to a maximum of 2.5 cm/sec in any application where this standard is
      invoked. There is some desire to eliminate or increase this media velocity limit.
      A concern is that increasing media velocity will result in higher emissions of
      ultrafine particles; thus, it is unlikely that higher media velocities will be
      allowed without data to demonstrate the effect of media velocity on removal of
      ultrafine particles. In this study, the performance of nuclear grade HEPA
      filters, with respect to filter efficiency and most penetrating particle size,
      was evaluated as a function of media velocity. Deep-pleat nuclear grade HEPA
      filters (31 cm x 31 cm x 29 cm) were evaluated at media velocities ranging from
      2.0 to 4.5 cm/sec using a potassium chloride aerosol challenge having a particle
      size distribution centered near the HEPA filter most penetrating particle size.
      Filters were challenged under two distinct mass loading rate regimes through the
      use of or exclusion of a 3 microm aerodynamic diameter cut point cyclone. Filter
      efficiency and most penetrating particle size measurements were made throughout
      the duration of filter testing. Filter efficiency measured at the onset of
      aerosol challenge was noted to decrease with increasing media velocity, with
      values ranging from 99.999 to 99.977%. The filter most penetrating particle size
      recorded at the onset of testing was noted to decrease slightly as media velocity
      was increased and was typically in the range of 110-130 nm. Although additional
      testing is needed, these findings indicate that filters operating at media
      velocities up to 4.5 cm/sec will meet or exceed current filter efficiency
      requirements. Additionally, increased emission of ultrafine particles is
      seemingly negligible.

PMID- 18726820
TI  - Positive and negative gaze perception in autism spectrum conditions.
AB  - Eyes are key social features providing a wealth of information about the
      attention, interest, emotion, and intention of others. Humans are typically very
      adept at detecting gaze direction, but there is a large decrement in gaze
      discrimination ability when eye images change from positive to negative polarity.
      This is thought to show an expert system for gaze perception that applies a
      contrast-specific heuristic to determine where someone else is looking. Autism
      spectrum conditions (ASC) are characterized by social deficits including
      difficulties in face-processing and in the social use of gaze. People with ASC
      are thought to have less expertise for gaze processing compared to typical
      controls, though little research has tested this. We investigated gaze direction
      perception in typical males and females, and males with ASC using facial stimuli
      with positive or negative polarity of the eyes. Results showed that the ASC group
      was worse at judging gaze direction with positive stimuli, and showed less of a
      decrement in performance when eye stimuli changed from positive to negative
      polarity. The differences in gaze perception for the ASC group were most evident
      when information from the eyes was more difficult and ambiguous. Typical females
      performed better at gaze direction detection with positive polarity than typical
      males, who in turn performed better than males with ASC. This latter finding is
      consistent with the extreme male brain theory of autism, and with the idea that
      people with ASC have less gaze expertise.

PMID- 18726821
TI  - Valuing intervention and observation.
AB  - Understanding causal relations is fundamental to effective action but causal data
      can be confounded. We examined the value that participants placed on data derived
      from a hypothetical intervention or observation. Our materials involved a
      possible cause ("bottled water"), a possible confound ("food"), and a context ("a
      restaurant"). We supposed that participants seek to draw as specific a causal
      inference as possible from presented data and value information sources more
      highly that allow them to do so. On this basis, we predicted that in
      circumstances where an intervention removed the confounding causal factor but
      observation did not, participants would prefer data derived from an intervention
      when the possible cause was present (the bottled water was drunk) but show the
      reverse preference when the possible cause was absent (the bottled water was not
      drunk). Experiment 1 confirmed this prediction. Using a between-subjects design,
      Experiment 2 tested for a difference in confidence in causal judgements given
      identical data, including data on the confound, as a function of method of data
      collection (intervention or observation). There was no significant difference in
      confidence ratings between the two methods but confidence ratings were sensitive
      to the probability of an effect (illness) given the cause. Using a within
      subjects design, Experiment 3 revealed systematic individual differences in
      preference for the two methods. Participants were divided between those who
      considered intervention more confounded and those who considered observation more
      confounded. Our experiments point to the subtleties of participants' evaluation
      of data from studies of human beings.

PMID- 18726822
TI  - Think, blink or sleep on it? The impact of modes of thought on complex decision
      making.
AB  - This paper examines controversial claims about the merit of "unconscious thought"
      for making complex decisions. In four experiments, participants were presented
      with complex decisions and were asked to choose the best option immediately,
      after a period of conscious deliberation, or after a period of distraction (said
      to encourage "unconscious thought processes"). In all experiments the majority of
      participants chose the option predicted by their own subjective attribute
      weighting scores, regardless of the mode of thought employed. There was little
      evidence for the superiority of choices made "unconsciously", but some evidence
      that conscious deliberation can lead to better choices. The final experiment
      suggested that the task is best conceptualized as one involving "online
      judgement" rather than one in which decisions are made after periods of
      deliberation or distraction. The results suggest that we should be cautious in
      accepting the advice to "stop thinking" about complex decisions.

PMID- 18726823
TI  - Exploring the time course of semantic interference and associative priming in the
      picture-word interference task.
AB  - The picture-word interference (PWI) task is a widely used technique for exploring
      effects of semantic context on lexical access. In this task, printed words are
      superimposed over pictures to be named, with the timing of the interfering word
      relative to the picture systematically manipulated. Two experiments (N = 24
      adults in each) explored the time course of effects of associates (e.g., CARROT
      superimposed on a picture of a rabbit) versus coordinates (e.g., CHIPMUNK
      superimposed on a picture of a rabbit) on naming latencies. Associates led to
      faster picture naming than did unrelated words, with facilitative effects
      occurring at stimulus onset asynchronies (SOAs, in ms) ranging from -450 to 0.
      Coordinates led to slower naming latencies, with the interference effect
      restricted to SOAs of -150 and 0. The overlapping time course of associative
      priming and coordinate interference provides important constraints on models of
      lexical access in speech production.

PMID- 18726825
TI  - Effects of leptin replacement on risk factors for cardiovascular disease in
      genetically leptin-deficient subjects.

PMID- 18726826
TI  - Human pancreatic islets express the purinergic P2Y11 and P2Y12 receptors.

PMID- 18726827
TI  - Modulation of 11beta-hydroxysteroid dehydrogenase expression by bombesin: a
      possible mechanism for glucocorticoid resistance in androgen independent prostate
      cancer.
AB  - Treatment with glucocorticoids is one of a limited number of options for androgen
      independent prostate cancer. Neuroendocrine differentiation has been shown to
      contribute to androgen-independent prostate cancer progression. To study the
      potential link between neuroendocrine differentiation and the glucocorticoid
      action, we investigated the effects of the product of neuroendocrine
      differentiation--bombesin on glucocorticoid metabolizing enzymes--11beta
      hydroxysteroid dehydrogenases in PC-3 cells. Our Western analysis, RT-PCR, and
      activity assays demonstrate that while 18-hour exposure to bombesin reduces
      11beta-hydroxy-steroid dehydrogenases-1 profiles (activities 25% less, protein
      level 29% lower, mRNA levels 45% lower), contrarily it increases 11beta
      hydroxysteroid dehydrogenases-2 profiles (activities 34%, protein levels 100%,
      mRNA levels 120%). Blockade bombesin action with bombesin receptor antagonists
      and the enzyme degrading bombesin prevented these changes, suggesting the
      observed modulations were bombesin receptor-specific. In addition, bombesin
      increased the amounts of interleukin-8 and mRNA of vascular endothelial growth
      factor receptor 2, which were lowered in the presence of cortisol, suggesting
      that neuropeptide blockade may extend the benefits of glucocorticoids in treating
      androgen-independent prostate cancer.

PMID- 18726828
TI  - Deconvolution of insulin secretion, insulin hepatic extraction post-hepatic
      delivery rates and sensitivity during 24-hour standardized meals: time course of
      glucose homeostasis in leptin replacement treatment.
AB  - Minimally invasive methodology, mathematical model, and software for analysis of
      glucose homeostasis by deconvolution of insulin secretion, hepatic extraction,
      post-hepatic delivery, and sensitivity from 24-hour standardized meals test have
      been developed and illustrated by the study of glucose homeostasis of a
      genetically based leptin-deficient patient before and after leptin replacement
      treatment. The only genetically leptin-deficient adult man identified in the
      world was treated for 24 months with recombinant methionyl human leptin. Blood
      was collected every 7 minutes for 24 hours, with standardized meals consumed
      during the 4 visits: at baseline, one-week, 18-months, and 24-months after
      initiation of the treatment. Concentrations of insulin, C-peptide, and plasma
      glucose were measured. Insulin secretion was obtained by deconvolution of C
      peptide data. Hepatic insulin extraction was determined based on our
      modifications of the insulin kinetics model . Insulin sensitivity for each of the
      four meals was calculated by using the minimal glucose model approach. Hepatic
      extraction of insulin was the first element of glucose homeostasis to respond to
      leptin replacement treatment and increased 2-fold after one week of treatment.
      Insulin secretion and delivery rates decreased more than 2-fold and insulin
      sensitivity increased 10-fold after 24 months of treatment. Computer programs for
      analysis of 24-hour insulin secretion, extraction, delivery, and action are
      available upon request.

PMID- 18726829
TI  - Efficacy and safety of vildagliptin monotherapy during 2-year treatment of drug
      naive patients with type 2 diabetes: comparison with metformin.
AB  - The present study was a 52-week extension of a previously published, multi
      center, randomized, parallel-group study. The aim of this extension study was to
      compare the efficacy and tolerability of vildagliptin and metformin in drug-naive
      patients with type 2 diabetes over 104 weeks. The extension population comprised
      305 patients randomized to vildagliptin (100 mg daily) and 158 patients
      randomized to metformin (2 000 mg daily). Pioglitazone was added as rescue
      medication if fasting glucose was >10 mmol/l; data from patients receiving rescue
      medication were excluded from the primary analysis. Baseline HbA (1c) averaged
      8.4+/-0.1% in patients randomized to vildagliptin and 8.8+/-0.1% in those
      randomized to metformin. The adjusted mean change from baseline to study endpoint
      was -1.0+/-0.1% in vildagliptin-treated patients and -1.5+/-0.1% in those
      receiving metformin (p<0.001 vs. vildagliptin). These results were similar to
      those reported after the 1-year core phase of the study. The adjusted mean
      changes in body weight from baseline to endpoint were 0.5+/-0.4 kg and -2.5+/-0.5
      kg in the vildagliptin and metformin groups, respectively. One or more adverse
      event (AE) was reported by 82.2% of patients receiving vildagliptin and by 87.3%
      of those receiving metformin (p<0.001). Gastrointestinal AEs were more common in
      patients receiving metformin (45.6%) than in those receiving vildagliptin (25.0%,
      p<0.001 vs. metformin). One hypoglycemic event occurred after strenuous exercise
      in a single patient receiving vildagliptin (0.3%). In conclusion, both
      vildagliptin and metformin monotherapy provided clinically meaningful decreases
      in HbA (1c) over 2 years in drug-naive patients with type 2 diabetes.
      Vildagliptin was weight neutral, while weight loss was observed with metformin;
      however, metformin was associated with significantly worse gastrointestinal
      tolerability.

PMID- 18726830
TI  - Impact of menstrual cycle phase on insulin sensitivity measures and fasting
      lipids.
AB  - There is evidence to suggest that insulin sensitivity may vary in response to
      changes in sex hormone levels. However, the results of human studies designed to
      investigate changes in insulin sensitivity through the menstrual cycle have
      proved inconclusive. The aims of this study were to 1) evaluate the impact of
      menstrual cycle phase on insulin sensitivity measures and 2) determine the
      variability of insulin sensitivity measures within the same menstrual cycle
      phase. A controlled observational study of 13 healthy premenopausal women, not
      taking any hormone preparation and having regular menstrual cycles, was
      conducted. Insulin sensitivity (Si) and glucose effectiveness (Sg) were measured
      using an intravenous glucose tolerance test (IVGTT) with minimal model analysis.
      Additional surrogate measures of insulin sensitivity were calculated
      (homoeostasis model for insulin resistance [HOMA IR], quantitative insulin-to
      glucose check index [QUICKI] and revised QUICKI [rQUICKI]), as well as plasma
      lipids. Each woman was tested in the luteal and follicular phases of her
      menstrual cycle, and duplicate measures were taken in one phase of the cycle. No
      significant differences in insulin sensitivity (measured by the IVGTT or
      surrogate markers) or plasma lipids were reported between the two phases of the
      menstrual cycle or between duplicate measures within the same phase. It was
      concluded that variability in measures of insulin sensitivity were similar within
      and between menstrual phases.

PMID- 18726831
TI  - The effect of recombinant aminopeptidase A on hypertension in spontaneously
      hypertensive rats: its effect in comparison with candesartan.
AB  - An understanding of aminopeptidase A in hypertension is important, given its
      ability to cleave the N-terminal aspartic acid of potent vasoconstrictor
      angiotensin II. However, the role of aminopeptidase A in hypertension has
      received limited attention. Because we have succeeded in producing recombinant
      human aminopeptidase A, the effect of aminopeptidase A on systolic blood pressure
      in the spontaneously hypertensive rat was examined. Aminopeptidase A of 0.016
      mg/kg was administrated intravenously to spontaneously hypertensive rats and
      blood pressure was monitored for 72 h. For repeated administration,
      aminopeptidase A doses of 0.016 mg/kg and 0.1-mg/kg doses of candesartan (an
      angiotensin II receptor 1 subtype blocker) were administrated daily in
      spontaneously hypertensive rats and blood pressure was monitored for 5 d. Bolus
      intravenous injection of aminopeptidase A at a dose of 0.016 mg/kg significantly
      decreased systolic blood pressure for 36 h in spontaneously hypertensive rats. A
      comparison of the antihypertensive effects of aminopeptidase A versus candesartan
      in spontaneously hypertensive rats showed that the effective dose of
      aminopeptidase A was about one-tenth that of candesartan. These results suggest
      the novel approach of utilizing aminopeptidase A to treat hypertension by
      degrading circulating angiotensin II before it binds to the receptor 1 subtype.

PMID- 18726832
TI  - Rapid reduction of liver steatosis in omega3-depleted rats injected with a novel
      lipid emulsion.
AB  - The bolus intravenous administration of a novel medium-chain triglyceride: fish
      oil emulsion (MCT:FO) to normal subjects was recently found to increase within 60
      min the amount of long-chain polyunsaturated omega3 fatty acids ( omega3) in
      platelet and leukocyte phospholipids and, hence, was proposed as a tool to
      prevent such pathological events as cardiac arrhythmia in selected patients who
      have to undergo urgent anesthesia and/or surgery. This study investigates whether
      other cells located outside the vascular bed may also benefit from this procedure
      for replenishing phospholipids with omega3. For such a purpose, the MCT:FO
      emulsion (1.0 ml) was injected into normal or omega3-depleted rats examined, one
      hour later, for the content and fatty acid pattern of liver triglycerides and
      phospholipids. Control experiments included the administration of saline or a
      medium-chain triglyceride:olive oil emulsion. The results reveal that the bolus
      intravenous injection of MCT:FO to the omega3-depleted rats resulted in the
      enrichment of liver phospholipids in omega3 and a marked reduction in hepatic
      steatosis. In conclusion, it is proposed that such a procedure may indeed allow a
      rapid supply of omega3 not only to circulating and vascular endothelial cells but
      also to extravascular cells, with a resulting correction of the biochemical and
      biophysical defects linked to a deficiency in these fatty acids.

PMID- 18726833
TI  - Idiopathic neonatal ischemia in the upper limb: the role of the microsurgeon.
AB  - Idiopathic neonatal limb ischemia remains a rare occurrence. It is a devastating
      process that leads to complete or partial loss of affected limb or severe
      deformity. The main treatments over the years have been conservative and
      nonsurgical, such thrombolysis. Surgical treatment has traditionally been delayed
      until a line of demarcation is clear, at which time amputation of the limb
      proceeds. We present a case of idiopathic upper limb ischemia in a newborn, where
      it was clear that nonsurgical management would result in limb necrosis. A
      thrombus extended from the brachial bifurcation into both ulnar and radial
      arteries to the wrist. The plastic surgery team performed surgical decompression
      and microsurgical open thrombectomy to successfully reestablish the circulation
      to the affected hand. Eight months later, the child remains well. This is the
      first reported case in the literature where an idiopathic thrombus blocking the
      brachial, radial, and ulnar arteries is successfully treated microsurgically.

PMID- 18726834
TI  - Pregnancy in women with renal disease. Part I: general principles.
AB  - The purpose of this review is to improve the basis upon which advice on pregnancy
      is given to women with renal disease and to address issues of obstetric
      management by drawing upon the accumulated world experience. To ensure the proper
      rapport between the respect for patient's autonomy and the ethical principle of
      beneficence, the review attempts to impart up-to-date, evidence-based information
      on the predictable outcomes and hazards of pregnancy in women with chronic renal
      disease. The physiology of pregnancy from the perspective of the affected kidney
      will be discussed as well as the principal predictors of maternal and fetal
      outcomes and general recommendations of management. The available evidence
      supports the implication that the degree of renal function impairment is the
      major determinant for pregnancy outcome. In addition, the presence of
      hypertension further compounds the risks. On the contrary, the degree of
      proteinuria does not demonstrate a linear correlation with obstetric outcomes.
      Management and outcome of pregnancies occurring in women on dialysis and after
      renal transplant are also discussed. Although the outcome of pregnancies under
      chronic dialysis has markedly improved in the past decade, the chances of
      achieving a viable pregnancy are much higher after transplantation. But even in
      renal transplant recipients, the rate of maternal and fetal complications remains
      high, in addition to concerns regarding possible adverse effects of
      immunosuppressive drugs on the developing embryo and fetus.

PMID- 18726835
TI  - Meningitis in preterm neonates: importance of cerebrospinal fluid parameters.
AB  - Cerebrospinal fluid parameters are of great importance in diagnosing meningitis,
      but normal values for preterm neonates are based on small, single-center studies.
      We sought to determine current values for preterm neonate cerebrospinal fluid
      parameters and assess the association of cerebrospinal fluid parameters with
      culture proven meningitis. We performed a cohort study of the first lumbar
      puncture from 4632 neonates < 34 weeks' gestation performed in the years 1997 to
      2004 at 150 neonatal intensive care units managed by the Pediatrix Medical Group.
      We identified 95 cases of meningitis from the 4632 lumbar punctures. The area
      under the receiver operating characteristic curves for white blood cell count,
      glucose, and protein were 0.80, 0.63, and 0.72, respectively, for prediction of
      culture-proven meningitis. Cerebrospinal fluid parameters used to diagnose
      meningitis in the absence of dependable cerebrospinal fluid cultures are
      unreliable. Caution should be employed when interpreting cerebrospinal fluid
      parameters in the premature neonate.

PMID- 18726836
TI  - Chorioamnionitis and ontogeny of circulating prostaglandin and thromboxane in
      preterm infants.
AB  - Our objective was to determine the effect of chorioamnionitis on plasma
      prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) during the first week in
      preterm infants. Plasma PGE2 and TxB2 were measured at 1, 3, and 7 days of age in
      preterm infants (birth weights 501 to 1500 g), with ( N = 26) and without ( N =
      22) chorioamnionitis. Infants with maternal chorioamnionitis had significantly
      lower mean gestational age ( P = 0.0001) and birth weight ( P = 0.03) and a
      marginally higher rate of bronchopulmonary dysplasia (37% versus 12.5, P = 0.05),
      a result that may be related to the lower mean gestational age. Plasma PGE2 and
      TxB2 varied widely, more so on the first day but did not significantly differ
      between the two groups. TxB2 was lower among infants who died or developed
      morbidities. Circulating PGE2 and TxB2 concentrations in preterm infants in the
      first week vary considerably, are relatively unaltered by chorioamnionitis, and
      are lower in association with mortality and clinical morbidities. Further
      research on their role in the causation of adverse neonatal outcomes is
      necessary.

PMID- 18726837
TI  - A case-control comparison of the effectiveness of betamethasone to prevent
      neonatal morbidity and mortality in preterm twin and singleton pregnancies.
AB  - We compared the effectiveness of antenatal betamethasone for the prevention of
      neonatal morbidity and mortality in preterm twin and singleton gestations. We
      conducted a case-control study of women with twin versus singleton gestations who
      received betamethasone for risk of prematurity in a university-affiliated,
      community-based, tertiary care center between 1997 and 2005. Cases were
      identified from clinical care and pharmacy databases, then matched for neonatal
      gender and gestational age (GA) at delivery. Sixty cases and 60 controls of
      deliveries occurring between 24 and 34 weeks' gestation were identified. The mean
      GA was 30.4 +/- 2.7 weeks. There were no differences between the groups in
      maternal demographics (with the exception of maternal age), birth weight, head
      circumference, Apgar scores, need for mechanical ventilation, days on ventilator,
      intraventricular hemorrhage grade 3 or 4, necrotizing enterocolitis suspected
      sepsis, total days in neonatal intensive care unit, or neonatal deaths. No
      differences in major morbidities or mortality were found in singletons versus
      twins. Concerns that the added maternal plasma volume in multiple gestations
      could lessen the neonatal benefits of antenatal betamethasone were not
      substantiated. This study may be affected by beta-error due to small sample size
      and sampling bias as a result of a retrospective study.

PMID- 18726839
TI  - Ultrasonography of imperforate anus in neonate: an approach correlated with
      current surgical concepts.
AB  - Neonates with an imperforate anus pose a challenge to those responsible for
      diagnosing and treating the congenital abnormality. Early assessment and accurate
      diagnosis of the type of imperforate anus are essential for determining the
      appropriate surgical procedure. Transperineal ultrasonography (US) can be used to
      identify the internal fistula and to define the type of imperforate anus. Thus,
      US represents an useful noninvasive imaging modality for assisting in the
      diagnosis and appropriate management of this disease. We will describe this
      imaging technique and present different types of illustrative scans of an
      imperforate anus.

PMID- 18726841
TI  - [Diagnosis of fibromatosis colli via color-coded duplex sonography in 13
      infants].
AB  - AIM: Fibromatosis colli is the most common cause of congenital torticollis.
      Patients show a solid tumor in the region of the sternocleidomastoid muscle which
      has to be differentiated from other congenital space-occupying lesions in the
      cervical region. PATIENTS AND METHOD: 13 infants (7 boys, 6 girls) with a mean
      age of 28 +/- 21 days with fibromatosis colli were examined with a high
      resolution linear transducer via color-coded duplex sonography. The location of
      the tumor within the sternocleidomastoid muscle, delineation from surrounding
      structures, the echogenicity, and the vascularization were estimated. 3 tumors
      were surgically removed, and the other 10 infants were treated conservatively
      with physiotherapy. RESULTS: The tumors were located on the right side in 10
      patients and on the left side in 3 infants. In 10 patients the tumor was located
      in the caudal part, in 3 in the middle part of muscle. All tumors showed a good
      delineation from the surrounding structures. The volume of the tumor was 5.4 +/-
      2.7 ml. 8 tumors showed inhomogeneous echogenicity, and 5 showed homogenous
      echogenicity. 9 tumors had echopoor, 3 echogenic, 1 isoechogenic internal echoes
      compared to the contralateral healthy muscle. 13 tumors showed increased
      perfusion (10 diffusely, 3 focally) via color-coded Doppler sonography.
      CONCLUSION: Diagnosis of fibromatosis colli can be affirmed sonographically. The
      tumors are commonly located in the distal 2 / 3 of the sternocleidomastoid muscle
      and show good delineation from surrounding structures. Typically an
      inhomogeneous, echopoor tumor with increased perfusion can be shown. Additional
      diagnostic imaging modalities are usually not necessary. The treatment of choice
      is physiotherapy. In special cases with a lack of improvement, surgery is
      necessary.

PMID- 18726842
TI  - Assessment of a biliary hamartoma with contrast-enhanced sonography using two
      different contrast agents.
AB  - A 49 year old male with carcinoma of the esophagus was staged using conventional
      US of the abdomen. US revealed signs of cirrhosis and a hyporeflexive focal liver
      lesion of about 5 mm in diameter was found. Low-MI contrast-enhanced ultrasound
      (CEUS) with SonoVue (Bracco, Milano, Italy) showed an enhancement pattern which
      was typical for benign liver lesions while high-MI CEUS with Levovist (Schering,
      Berlin, Germany) revealed a contrast defect in the liver late phase (4:30 min p.
      i.) which is typical for a malignant lesion. Due to these findings the lesion was
      evaluated as a potentially malignant lesion and a biopsy was performed. Histology
      showed a benign biliary hamartoma and incomplete cirrhosis. The findings
      confirmed that liver-specific contrast agents have the ability to detect very
      small focal liver lesions not derived from hepatic tissue but may lead to a
      misinterpretation as a malignant lesion. Nevertheless biliary duct adenomas are
      benign lesions with almost the same perfusion properties as normal liver
      parenchyma. Therefore, while using SonoVue, such a misinterpretation of these
      very common but in most cases very small and not detectable lesions seems
      unlikely.

PMID- 18726843
TI  - [Involuntary placement and coercive treatment in Germany. Subtle differences
      within the legal framework].

PMID- 18726844
TI  - [Methods for assessing impaired insight in Alzheimer's disease--a critical
      review].
AB  - OBJECTIVE: Impaired insight (anosognosia) is frequently present in Alzheimer's
      disease. However, established instruments for diagnosing anosognosia are lacking.
      METHOD: This article reviews the literature on impaired insight in Alzheimer's
      disease with a focus on assessment methods that have been applied to its study.
      RESULTS: The primary methods for assessing anosognosia are clinical judgment,
      comparison of patient and caregiver reports, and comparison of patients' self
      assessment and task performance. CONCLUSIONS: While simple approaches such as
      expert rating scales can be appropriate for clinical practice, more elaborate
      procedures in research may shed light on the cognitive mechanisms involved in
      anosognosia. Previous results have shown that unawareness of deficits affects
      cognitive and emotional domains as well as activities of daily living, thus any
      diagnostic instrument should capture these different aspects. However,
      methodological issues such as the objectivity of caregiver reports or patients'
      ability to assess their own performance need to be considered in order to obtain
      reliable data.

PMID- 18726845
TI  - [Extra-medullary hematopoiesis: imaging findings].

PMID- 18726860
TI  - [Change in the contract physician regulation--greater employment freedom for the
      established radiologist?].

PMID- 18726862
TI  - [Therapy of a schwannoma of the vagal nerve--stated at the example of an
      extensive tumor].
AB  - INTRODUCTION: Schwannoma of the vagal nerve are rare and usually accidentally
      found by exploring a slowly growing and painless neck tumor. CASE: We report on a
      49-year-old patient with an extensive schwannoma of the vagal nerve. The tumor
      grew from the brainstem to the lower neck vessel sheath and destroyed the skull
      base. The tumor had already involved all nerves of the foramen jugulare. The
      surgery was performed in cooperation with the neurosurgeons. Initially the
      cervical part of the tumor was removed by transcervical approach. Then the
      endocranial part of the tumor was removed by retrosigmoidal craniotomy and
      partial petrosectomy. DISCUSSION: We have observed 5 schwannomas of the vagal
      nerve in 47,000 patients for 16 years. The diagnostic and therapeutic procedure
      is determined by the preoperative nerve function. In case of an intact nerve and
      after verifying the diagnosis of a schwannoma a detailed information given to the
      patient is absolutely necessary before any intervention. If the nerve lost its
      function there are no contraindications to resect the tumor and the nerve. Tumors
      with an intracranial extension should be treated interdisciplinarily
      (ENT/neurosurgery).

PMID- 18726863
TI  - [From the expert's office: new jurisdiction in the German social law for the
      methodology in expert opinions].

PMID- 18726864
TI  - [The sense of smell in daily life].
AB  - An intact olfactory system affects all areas of life including the creation of
      new life, partner selection, daily hygiene, food intake, and the perception of
      danger from gas and smoke. The olfactory system is most effective from
      adolescence to middle age. With advancing age the regeneration of olfactory
      receptor cells decreases, often resulting in an increasing loss of smell.
      Functional anosmia affects 5% of the general population and 10% of those over 65.
      Therefore, olfactory dysfunctions are not uncommon. The following provides an
      overview of the physiology of smell, olfactory testing, special olfactory
      dysfunctions as well as treatment and general recommendations.

PMID- 18726865
TI  - Foot temperature in type 2 diabetic patients with or without peripheral
      neuropathy.
AB  - The aim of this study was to evaluate foot temperature in type 2 diabetic
      patients with vs. without peripheral neuropathy. The study included 30 patients
      (group A: 16 men, mean age 63.23+/-7.02 years) with peripheral neuropathy and 30
      patients (group B: 17 men, mean age 62.37+/-6.73 years) without peripheral
      neuropathy. Neuropathy was diagnosed by the Diabetic Neuropathy Index (DNI). Foot
      temperature was measured with a handheld infrared thermometer (KM 814, Kane-May,
      UK) on the mid-dorsal aspect of the foot (dorsal temperature) and on the plantar
      aspect of the foot at the level of the first metatarsal head (plantar
      temperature). Dorsal temperature was significantly higher in group A than in
      group B (right foot 32.89+/-1.02 degrees C vs. 31.2+/-1.07 degrees C, p<0.001).
      The same significant difference was observed for the plantar temperature (32.2+/
      0.94 degrees C vs. 30.7+/-1.07 degrees C, p<0.001). In both groups, a significant
      positive correlation was observed between dorsal and plantar temperature (group
      A: r (s)=0.913, p<0.001; group B: r (s)=0.956, p<0.001). Finally, in group A, DNI
      score showed a significant positive correlation with dorsal temperature (r
      (s)=0.856, p<0.001), as well as plantar temperature (r (s)=0.859, p<0.001).
      CONCLUSIONS: Foot temperature is significantly higher in type 2 diabetic patients
      with neuropathy as compared to those without neuropathy. In patients with
      neuropathy, a significant positive correlation is observed between foot
      temperature and clinical severity of neuropathy.

PMID- 18726866
TI  - Genetic variability of procolipase associates with altered insulin secretion in
      non-diabetic Caucasians.
AB  - AIMS: Procolipase (CLPS) is secreted from the exocrine pancreas into the
      gastrointestinal tract and becomes proteolytically cleaved into colipase and the
      pentapeptide enterostatin. While colipase is an indispensable cofactor for
      pancreatic lipase, enterostatin acts as a hormone that inhibits insulin secretion
      and confers satiety signals to the brain, thereby restricting further food intake
      in animal models. As both high fat diet and obesity contribute to insulin
      resistance, we investigated whether genetic variability of CLPS associates with
      metabolic traits in non-diabetic humans at diabetes risk. METHODS: Tagging single
      nucleotide polymorphisms (SNPs) in the human CLPS locus on chr6p21.1 were
      selected using HapMap data. 498 humans, phenotyped for different glucose and
      lipid metabolic traits, were genotyped by bidirectional sequencing and
      multivariate linear regression analyses were undertaken. RESULTS: 2 tagging SNPs
      (rs3748050 in the Kozak sequence: A/G and rs3748051 in intron 1: A/G), covering
      100% of CLPS variability including 8 kb of its promoter, were genotyped for
      association analyses. The minor alleles of both tagging SNPs associated
      significantly with a reduced insulin secretion (-20.2%, both SNPs) in various
      estimation models derived from the oral glucose tolerance test (OGTT;
      rs3748050/51: 30 min C-peptide levels: p=0.001/0.01, insulinogenic index:
      p=0.02/0.02, AUC C-peptide/AUC glucose: p=0.01/0.01) after adjustment for
      relevant covariates. No significant associations with fasting total cholesterol
      (c), HDL-c, LDL-c, triglycerides and free fatty acids were found (all p > 0.11).
      CONCLUSIONS: CLPS genetic variability associates with insulin secretory function
      in non-diabetic humans and may represent a novel candidate gene for development
      of type 2 diabetes.

PMID- 18726868
TI  - Time trends in type 2 diabetes patients' disease management and outcomes:
      evidence from two KORA surveys in Germany.
AB  - To explore time trends in diabetes management and intermediate health outcomes of
      people with type 2 diabetes, data from two population-based survey studies were
      compared. The surveys were conducted in the Augsburg region of Southern Germany
      in 1997/98 and in 2004/05, and included physical examinations, interviews, self
      administered questionnaires and laboratory tests. Data from 334 participants aged
      40-84 were analysed, including a longitudinal sub-sample of 50 persons. Results
      show significant time trends towards improvements over the seven year period.
      Controlling for age, sex, education and duration of diabetes, people felt better
      informed about diabetes (Odds Ratio (OR) 1.87; 95% CI: 1.12, 3.14) and stated
      greater adherence to the treatment plan (OR 4.42; CI: 2.62, 7.45) as well as
      higher participation in diabetes education programmes (OR 2.20; CI: 1.44, 3.38).
      Mean haemoglobin A1c levels decreased by -0.97% from 7.3% to 6.3% (CI:-0.66%, 
      1.28%). Physical activity (> or =1 h/week) was more frequent (OR 2.75; CI: 1.65,
      4.59), although Body Mass Index increased by 1.43 kg/m (2) (CI: 0.86, 2.00). The
      positive changes in disease management and metabolic outcomes for type 2 diabetic
      patients between 1997/98 and 2004/05 indicate a shift towards greater patient
      involvement in diabetes care and possibly more efficient medical management
      practices.

PMID- 18726867
TI  - The L162V polymorphism of the peroxisome proliferator activated receptor alpha
      gene (PPARA) is not associated with type 2 diabetes, BMI or body fat composition.
AB  - BACKGROUND: The L162V single nucleotide polymorphism in PPARA is suggested to
      play an important role in the pathogenesis of type 2 diabetes, obesity, and body
      fat composition. However, clinical evidence is controversial. OBJECTIVE: Our aim
      was to investigate the relationships of the L162V SNP with type 2 diabetes, pre
      diabetes phenotypes, adiposity, and plasma lipid levels. In addition, we studied
      the associations of the L162V SNP with body fat composition, intramyocellular
      lipids, and liver fat content. Furthermore, we examined if the L162V SNP was
      associated with changes in BMI, insulin secretion, insulin resistance, body fat
      composition, intramyocellular lipids, and liver fat content in response to
      lifestyle intervention. MATERIAL AND METHODS: Data from two large cross sectional
      studies, the combined TULIP/TUEF cohorts, and the LURIC study were analysed.
      Prospective data were obtained from TULIP participants who underwent a lifestyle
      intervention. A total of 4,779 subjects were studied. BMI was measured in all
      subjects. Type 2 diabetes was diagnosed in a subgroup of the LURIC study. In the
      TULIP study total body fat, non-visceral adipose tissue, and visceral adipose
      tissue were measured with magnetic resonance tomography. Liver fat and
      intramyocellular lipid content were quantified with (1)H magnetic resonance
      spectroscopy. Insulin sensitivity and insulin secretion were estimated from oral
      glucose tolerance testing. RESULTS: The L162V SNP was neither associated with
      type 2 diabetes or BMI nor with body fat composition, intramyocellular lipids or
      liver fat content. CONCLUSIONS: According to our study, the L162V SNP does not
      have a strong impact on the pathogenesis of type 2 diabetes or obesity.

PMID- 18726869
TI  - Metabolic carcinogenesis in the Maltese population.
AB  - Endometrial adenocarcinoma has been associated with prolonged oestrogen exposure
      causing endometrial hyperplasia and adenocarcinoma. Metabolic disorders and
      nutritional factors may contribute towards obesity and the increased adipose
      production of oestrogen. The study confirms the association between endometrial
      carcinoma risk and diabetes mellitus and increased total fat intake. It further
      relates the malignancy to a prolonged natural oestrogen exposure period and
      confirms the protective role of past pregnancies.

PMID- 18726871
TI  - Vaspin (SERPINA12) genotypes and risk of type 2 diabetes: Results from the
      MONICA/KORA studies.
AB  - Vaspin has recently been identified as novel adipokine with high expression in
      adipose tissue of obese and type 2 diabetic subjects and with potentially insulin
      sensitising properties. However, the impact of vaspin gene variants on the risk
      of type 2 diabetes mellitus (T2DM) has not been determined yet. Therefore, the
      aim of our study was to investigate the association of vaspin single nucleotide
      polymorphisms (SNPs) with T2DM and obesity. We analysed the association between
      25 vaspin SNPs and T2DM in initially healthy 35-84 year-old individuals of the
      population-based, cross-sectional German KORA F3 study and assessed the
      association with measures of obesity. Genotyping was carried out with matrix
      assisted laser desorption/ionisation-time of flight mass spectrometry of allele
      dependent primer extension products and associations with T2DM and obesity were
      analysed by logistic regression analysis. Our results demonstrate a significant
      association of vaspin SNP rs2236242 with T2DM in the KORA F3 study with the AA
      genotype bearing an increased risk (adjusted OR 2.35 [1.59; 3.46] versus AT/TT).
      This association appears to be independent of obesity. Our finding corroborates
      previous studies that suggested a link between the novel adipokine vaspin and
      glucose metabolism.

PMID- 18726872
TI  - Nitrosylated proteins in monocytes as a new marker of oxidative-nitrosative
      stress in diabetic subjects with macroangiopathy.
AB  - BACKGROUND: Peroxynitrite plays an important role in the pathogenesis of diabetic
      complications. Nitrosylated protein expression in peripheral blood monocytes
      reflects intracellular peroxynitrite injury, and thus could be a marker of higher
      diagnostic and prognostic value than plasma nitrotyrosine level. The purpose of
      this pilot study was to assess if peripheral blood monocytes of diabetic subjects
      accumulate nitrosylated proteins, and if nitrosylated protein expression
      correlates with blood glucose control, variables of lipid profile, C-reactive
      protein concentration (a marker of inflammation), and differs in patients with
      and without diabetic macrovascular and microvascular complications. METHODS:
      Nitrosylated protein expression in peripheral blood monocytes (Western blot
      analysis) was assessed in 31 subjects with diabetes mellitus (29 Type 2, 2 Type
      1; 20 males, 11 females; mean age 66 years). The presence of microangiopathy was
      defined by retinopathy, albumin excretion, and/or neuropathy, and macroangiopathy
      by carotid plaques, a history of myocardial infarction, and/or stroke. RESULTS:
      Diabetic subjects accumulated significant amounts of nitrosylated proteins in
      peripheral blood monocytes. Nitrosylated protein expression positively correlated
      with body weight, blood glucose, HbA (1)C, and plasma C-reactive protein
      concentrations in the whole cohort as well as in subjects with diabetic
      macroangiopathy. CONCLUSIONS: Monocyte nitrosylated protein expression is a new
      biomarker of metabolic control and inflammation in diabetic subjects with
      macroangiopathy. A more detailed assessment of diabetic microvascular
      complications in a larger group of patients is needed to determine if this
      variable can be employed as a biomarker of the presence, severity, and
      progression of diabetic neuropathy, retinopathy, and nephropathy.

PMID- 18726873
TI  - Increased aldosterone levels in a model of type 2 diabetes mellitus.
AB  - BACKGROUND: Aldosterone is an important mediator of cardiovascular and renal
      remodeling. Type II diabetes mellitus leads to renal and cardiac end organ
      damage. We investigated the renin-angiotensin-aldosterone system in a model of
      type 2 diabetes mellitus with known diabetic nephropathy and cardiac remodeling,
      the Zucker Diabetic Fatty rat with and without ACE-inhibition (ZDF and ZDF+ACE-I)
      and its control, the Zucker Lean (ZDL) rat. METHODS: Male animals were studied
      from an age of 7-24 weeks. At ages 7, 14, 17, 20, and 23 weeks, urinary excretion
      of aldosterone-glucuronide and potassium was assessed. ACE-inhibition with
      ramipril was started orally at week 13 (1 mg/kg/d). At the end of the study rats
      were sacrificed and plasma aldosterone concentration and plasma renin activity
      were measured. Aldosterone synthase (CYP11B2) mRNA expression in the adrenals,
      kidney, heart and adipose tissue was assessed by real-time PCR. Urinary albumin
      excretion as marker for diabetic nephropathy was measured in metabolic cages and
      correlated to aldosterone. RESULTS: Plasma aldosterone concentration and
      aldosterone-glucuronide was significantly elevated in ZDF rats, and significantly
      reduced by ACE-inhibiton. In contrast, plasma renin activity was significantly
      reduced in ZDF rats and normalized by ACE-inhibition. The urinary aldosterone
      correlated significantly to albuminuria. Adrenal CYP11B2 expression was not
      significantly higher in ZDF rats. CYP11B2 mRNA was not detected in the kidney,
      heart and adipose tissue. CONCLUSION: In ZDF rats, urinary and plasma aldosterone
      levels were elevated despite reduced plasma renin activity. The reversible effect
      of ACE-inhibition shows that the up-regulation of aldosterone must be dependent
      of the renin-angiotensin-system in this type II diabetes model. The correlation
      between aldosterone and diabetic nephropathy suggests a clinical relevance of
      this observation.

PMID- 18726874
TI  - Insulinotropic effect of aqueous extract of Brassica nigra improves glucose
      homeostasis in streptozotocin induced diabetic rats.
AB  - Aqueous extract of BRASSICA NIGRA (AEBN) has been shown to have good antidiabetic
      effect along with significant decrease (p<0.01) of abnormal serum lipid levels in
      our previous study. To understand the mechanism of action, effect of oral
      administration of AEBN for two months on glycolytic and gluconeogenic enzymes was
      studied in liver and kidney tissues of rats with streptozotocin (STZ) induced
      diabetes mellitus. The activities of gluconeogenic enzymes were higher and of
      glycolytic enzymes were decreased in both the liver and kidney tissues during
      diabetes. However, in diabetic rats treated with AEBN for two months, decrease of
      serum glucose, increase of serum insulin and release of insulin from pancreas
      (shown in vitro from isolated pancreas) along with the restoration of key
      regulatory enzyme activities of carbohydrate metabolism and glycogen content were
      observed. The therapeutic role of AEBN in STZ induced diabetes as exemplified in
      this study can be attributed to the release of insulin from pancreas and change
      of glucose metabolizing enzyme activities to normal levels, thus stabilizing
      glucose homeostasis in the liver and kidney. The LD50 was found to be more than
      15 times the effective dose (ED) implying higher margin of safety for AEBN. These
      biochemical effects indicate that AEBN could be a possible new therapeutic agent
      for the treatment of diabetes.

PMID- 18726875
TI  - [Severe course of a rare non-tuberculous Mycobacteriosis (M. haemophilum) of the
      hand - case report and strategic comments].
AB  - INTRODUCTION: Mycobacterium haemophilum belongs to the group of atypical
      mycobacteria and is rarely reported as a cause of upper extremity and hand
      infections. It is of low virulence. The bacterium seems to be ubiquitous. Sources
      and mechanism of infection are poorly defined. CASE REPORT: A 48-year-old female
      patient was admitted with chronic flexor tendon synovitis of the left palm and
      distal forearm site. Three debridements were carried out and wound swabs were
      taken. No proof of bacterial colonisation was found. Histologically a
      granulomatous infection with Langerhans cells was revealed. Effectively
      calculated monotherapy with ciprofloxacin was begun. Six weeks postoperatively
      Mycobacterium haemophilum was cultivated in a colaboration with the National
      Reference Centre for Mycobacteria in Borstel. Medication was changed to triple
      therapy with clarithromycin, ethambutol and rifabutin. The patient could carry
      out her daytime job three months postoperatively. One year after first admission
      functional impairment needed to be treated by scar excision and radical flexor
      tendon tendolysis. The palmar defect was resurfaced by using a transmetacarpal
      DMCA 2 flap at the same time. An almost full range of motion was achieved with
      intensive hand and physiotherapy after a total treatment period of 15 months.
      DISCUSSION: Patients with upper extremity infections caused by atypical
      Mycobacteria need qualified hand-surgical care. The decision about need and kind
      of medicamentous treatment is based on germ differentiation and should be made in
      cooperation with the National Reference Centre for Mycobacteria in Borstel. To
      shorten the diagnostic gap between first admission and detection of Mycobacteria
      in hand infections with a non-typical course of disease we suggest a standardised
      approach.

PMID- 18726876
TI  - [Breast reconstruction with autologous tissue: current operative standards and
      new techniques].

PMID- 18726877
TI  - Polyethyleneimine-functionalized platinum nanoparticles with high
      electrochemiluminescence activity and their applications to amplified analysis of
      biomolecules.
AB  - Polyethyleneimine-functionalized platinum nanoparticles (PtNPs) with excellent
      electrochemiluminescence (ECL) properties were synthesized and applied to the
      amplified analysis of biomolecules. These particles were prepared at room
      temperature, with hyperbranched polyethyleneimine (HBPEI) as the stabilizer. The
      UV/Vis absorption spectra and transmission electron microscopy images clearly
      confirmed the formation of monodisperse PtNPs. Such particles proved to possess
      high stability against salt-induced aggregation, enabling them to be employed
      even under high-salt conditions. Owing to the existence of many tertiary amine
      groups, these particles exhibited excellent ECL behavior in the presence of
      tris(2,2'-bipyridyl)ruthenium(II). An HBPEI-coated particle possessed an ECL
      activity that was at least 60 times higher than that of a tripropylamine
      molecule. Furthermore, these particles could be immobilized on the 3
      aminopropyltriethoxysilane-treated quartz substrates to amplify the binding sites
      for carboxyl groups. Through this approach, PtNPs were applied to the amplified
      analysis of the hemin/G-quadruplex DNAzyme by using the luminol/H(2)O(2)
      chemiluminescence method.

PMID- 18726878
TI  - Luminescence resonance energy transfer sensors based on the assemblies of
      oppositely charged lanthanide/gold nanoparticles in aqueous solution.
AB  - This work demonstrates luminescence resonance energy transfer (LRET) sensors
      based on lanthanide-doped nanoparticles as donors (D) and gold nanoparticles as
      acceptors (A), combined through electrostatic interactions between the oppositely
      charged nanoparticles. Negatively charged lanthanide-doped nanoparticles,
      YVO(4):Eu and LaPO(4):Ce,Tb, with high luminescence quantum yield and good water
      solubility, are synthesized through a polymer-assisted hydrothermal method.
      Positively charged polyhedral and spherical gold nanoparticles exhibit surface
      plasmon resonance (SPR) bands centered at 623 and 535 nm, respectively. These
      bands overlap well with the emission of the Eu(3+) and Tb(3+) ions within the
      lanthanide nanoparticles. Herein, the gold nanoparticles are synthesized through
      a seed-mediated cetyltrimethylammonium bromide (CTAB)-assisted method. The
      assemblies of the oppositely charged donors and acceptors are developed into LRET
      based sensors exhibiting a donor quenching efficiency close to 100 %.

PMID- 18726879
TI  - The eligibility for local-regional treatment of peritoneal surface malignancy.
AB  - At the Fifth International Workshop on Peritoneal Surface Malignancy, held in
      Milan, the consensus on technical aspects of cytoreductive surgery (CRS) for
      peritoneal surface malignancy was obtained through the Delphi process. General
      conflicting points concerning the eligibility to the local-regional therapy were
      discussed and voted.

PMID- 18726881
TI  - Preoperative investigations in the management of peritoneal surface malignancy
      with cytoreductive surgery and perioperative intraperitoneal chemotherapy: Expert
      consensus statement.
AB  - At the Fifth International Workshop on Peritoneal Surface Malignancy, in Milan,
      the consensus on preoperative investigations for peritoneal surface malignancy
      was obtained through the Delphi process. The results showed that 100% of the
      voters considered that contrast-enhanced multi-sliced CT was the fundamental
      imaging modality, whereas MRI, PET, laparoscopy and serum tumor markers were
      regarded as useful, but not fundamental investigational modalities.

PMID- 18726880
TI  - Occupational allergy and asthma among salt water fish processing workers.
AB  - BACKGROUND: Fish processing is a common economic activity in Southern Africa. The
      aim of this study was to determine the prevalence and host determinants of
      allergic symptoms, allergic sensitization, bronchial hyper-responsiveness and
      asthma among workers processing saltwater fish. METHODS: A cross-sectional study
      was conducted on 594 currently employed workers in two processing plants involved
      in pilchard canning and fishmeal processing. A modified European Community
      Respiratory Health Survey (ECRHS) questionnaire was used. Skin prick tests (SPT)
      used extracts of common airborne allergens, fresh fish (pilchard, anchovy,
      maasbanker, mackerel, red eye) and fishmeal. Spirometry and methacholine
      challenge tests (MCTs; tidal breathing method) used ATS guidelines. RESULTS: Work
      related ocular-nasal symptoms (26%) were more common than asthma symptoms (16%).
      The prevalence of atopy was 36%, while 7% were sensitized to fish species and 26%
      had NSBH (PC(20) < or = 8 mg/ml or > or =12% increase in FEV(1) post
      bronchodilator). The prevalence of probable occupational asthma was 1.8% and fish
      allergic rhino-conjunctivitis 2.6%. Women were more likely to report work-related
      asthma symptoms (OR = 1.94) and have NSBH (OR = 3.09), while men were more likely
      to be sensitized to fish (OR = 2.06) and have airway obstruction (OR = 4.17).
      Atopy (OR = 3.16) and current smoking (OR = 2.37), but not habitual seafood
      consumption were associated with sensitization to fish. CONCLUSIONS: Based on
      comparison with previous published studies, the prevalence of occupational asthma
      to salt water fish is lower than due to shellfish. The gendered distribution of
      work and exposures in fish processing operations together with atopy and
      cigarette smoking are important determinants of occupational allergy and asthma.

PMID- 18726882
TI  - The intraoperative staging systems in the management of peritoneal surface
      malignancy.
AB  - The establishment of a rationale guideline for intraoperative staging system the
      extent of carcinomatosis is warranted. The quantitation of tumor found at the
      time of surgical exploration of the abdomen has proven to be of value in
      assessment of prognosis and treatment planning in patients with peritoneal
      carcinomatosis. Four different assessments systems have been employed more
      frequently, thus far. The advantages and disadvantages of each classification
      systems are described and discussed. The results of the Consensus of the last 5th
      International Workshop on Peritoneal Surface malignancy of Milan, December 2006
      are presented.

PMID- 18726883
TI  - Technical aspects of cytoreductive surgery.
AB  - At the Fifth International Workshop on Peritoneal Surface Malignancy, in Milan,
      the consensus on technical aspects of cytoreductive surgery (CRS) for peritoneal
      surface malignancy was obtained through the Delphi process. Five conflicting
      points were discussed: radicality of the peritonectomy procedure, cytoreduction
      of neoplastic nodules <2.5 mm, the timing of bowel anastomoses in relation to
      hyperthermic intraperitoneal chemotherapy (HIPEC) and indications of protective
      ostomies. According to the panel of experts a partial parietal peritonectomy
      restricted to the macroscopically involved regions could be indicated in all
      listed clinical conditions with the exception of peritoneal mesothelioma. No
      expert was of the opinion that a radical parietal peritonectomy is advisable
      irrespective of the disease being treated. All the experts agreed that
      electrovaporization of small (<2.5 mm) non-infiltrating metastatic nodules in the
      mesentery would be appropriate, even if theoretically the HIPEC affords
      microscopic cytoreduction. The panel also agreed that in the closed technique for
      HIPEC administration the intestinal anastomoses should be fashioned after
      completion of the perfusion. Finally when considering the place for protective
      ostomies the experts voted for a flexible approach allowing the surgeon to
      exercise discretion for individual patients.

PMID- 18726884
TI  - Postoperative residual disease evaluation in the locoregional treatment of
      peritoneal surface malignancy.
AB  - BACKGROUND: The maximum size of the residual lesions left behind after
      cytoreductive surgery for peritoneal surface malignancy has consistently been
      shown to be the main prognostic factor in this setting. However, a uniform
      assessment method and categorization for this paramount prognostic indicator is
      lacking. METHODS: In order to achieve a consensus among experts, the Delphi
      methodology was employed. Conflicting points were identified and related multiple
      choice questions were circulated among a panel of experts on peritoneal surface
      oncology. Two rounds of web-based voting were carried out. RESULTS: The
      completeness of cytoreduction (CC) Score described by Sugarbaker was considered
      the current best classification for residual disease size. The experienced
      surgeon's naked-eye estimation was considered the ideal method to assess residual
      disease size. There was agreement that the definition of CC-0 or R0 cytoreduction
      needs further specification. A redefinition of "completeness of cytoreduction"
      according to disease process was favored by the experts but not favored for the
      type of intraperitoneal chemotherapy employed. CONCLUSIONS: Following the
      experts' consensus, it is recommended that the CC score be used to categorize
      residual disease after cytoreductive surgery for peritoneal surface malignancy.
      Pending issues for further consensus development in this area have been
      identified.

PMID- 18726885
TI  - Hyperthermic intraperitoneal chemotherapy: nomenclature and modalities of
      perfusion.
AB  - Following international consensus, HIPEC should be the acronym used in the
      scientific literature to refer to the hyperthermic intraperitoneal chemotherapy.
      Several modalities of perfusion are used to deliver HIPEC: open abdominal
      technique (Coliseum), closed abdominal technique, peritoneal cavity expander,
      semi-opened abdominal technique. There is no sufficient evidence in literature
      confirming the superiority of one technique over the others in terms of outcome,
      morbidity and safety to the personnel of the operating theatre. Each option has
      its own operational advantages and disadvantages and future prospective studies
      must be conducted to establish which one is the best alternative. Today, the best
      technique is the one which is routinely used and improved into each specialized
      institution involved in the management of peritoneal surface malignancy.

PMID- 18726886
TI  - Drugs, carrier solutions and temperature in hyperthermic intraperitoneal
      chemotherapy.
AB  - At the Fifth International Workshop on Peritoneal Surface Malignancy, in Milan,
      the consensus on technical aspects of cytoreductive surgery (CRS) for peritoneal
      surface malignancy was obtained through the Delphi process. Conflicting points
      concerning drugs, carrier solution and optimal temperature for hyperthermic
      intraperitoneal chemotherapy (HIPEC) were discussed.

PMID- 18726887
TI  - Morbidity, toxicity, and mortality classification systems in the local regional
      treatment of peritoneal surface malignancy.
AB  - To reach a consensus for reporting complications related to cytoreductive surgery
      (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Reporting the
      adverse events related to CRS + HIPEC is not standardized yet. Post-operative
      complications can be divided in two categories: the effects of surgical
      manipulation per se and the toxic effects of the heated intraoperative
      chemotherapy. Additive and/or synergistic effects also exist. Different centers
      have published their experience with regard to the complications associated with
      the procedure. Various classification systems have been used which makes a
      temptative comparison of the different techniques and results almost impossible.
      An effort was made here to review the existing major classification systems: The
      Bozzetti classification, the Clavien classification (and two proposed
      modifications from Feldman et al. and Elias et al.) and the Common terminology
      criteria for adverse events (CTCAE) version 3.0 of the National Institute of
      Health (NIH) criteria. A related document was sent to an international panel of
      experts. The CTCAE was adopted by the panel of experts as the unique
      classification system to be used for reporting complications related to CRS +
      HIPEC.

PMID- 18726888
TI  - The Fifth International Workshop on Peritoneal Surface Malignancy (Milan, Italy,
      December 4-6, 2006): methodology of disease-specific consensus.
AB  - Peritoneal surface malignancies (PSM) have been traditionally regarded as
      uniformly terminal conditions. The combination of cyto-reductive surgery and
      perioperative intraperitoneal chemotherapy has changed PSM management from
      palliation to possible cure. Due to the inherent differences in biological and
      clinical behavior, the optimal adaptation of comprehensive treatment to each PSM
      is still a matter of debate. A session of "The Fifth International Workshop on
      Peritoneal Surface Malignancy" (Milan, Italy, December 4-6, 2006) was committed
      to reach a consensus pertaining to conceptual and technical aspects of the loco
      regional treatment of each PSM. The consensus developing process was based on
      principles of the Delphi method. A total of 103 international experts from 17
      countries were included in six Working Groups (WG) for each of the following PSM:
      peritoneal mesothelioma, abdominal sarcomatosis, carcinomatosis of gastric, colo
      rectal, appendiceal, and ovarian origin. Evidence reports were written by the
      respective WG. The main conflicting points (CP) regarding preoperative
      evaluation, patient eligibility, combined treatment methodology, postoperative
      follow-up and future investigational perspectives were summarized as a list of
      multiple-choice questions. Overall, 160 CP were identified. A consensus >or=51%
      of voters favoring one option was reached in 143/160 CP (89.4%). The general
      treatment guidelines and future investigational perspectives were defined.

PMID- 18726889
TI  - Consensus statement on the loco regional treatment of colorectal cancer with
      peritoneal dissemination.
AB  - Medical management with combinations of cytotoxic chemotherapy, and/or biological
      agents, has resulted in an unprecedented median survival >20 months in patients
      with Stage IV colorectal cancer. The management of disease limited to the
      peritoneal cavity has been controversial and at the present time, there is no
      published data that outlines the impact of these new therapeutic regimens when
      given to patients with colorectal cancer with metastatic disease confined to the
      peritoneum. Over the last 5 years, an increasing number of international
      treatment centers have published their prospective results using cytoreductive
      surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in the management
      of peritoneal surface malignancies of colorectal origin and have shown that good
      long-term results can be achieved with a complete cytoreduction and HIPEC.
      However, most of the surgical data comes from Phase II studies from single
      institutions and there is a wide range on inclusion/exclusion criteria, drugs,
      temperatures and methods of delivering the heated chemotherapy. This manuscript
      will analyze and discuss the results of a group of health care providers trying
      to achieve a consensus statement in the management of this group of patients.

PMID- 18726890
TI  - Consensus statement on peritoneal mesothelioma.
AB  - Diffuse malignant peritoneal mesothelioma (DMPM) has been traditionally regarded
      as a rapidly lethal disease. Recently, several independent prospective trials
      have reported improved survival with an intensive loco-regional treatment
      strategy including cytoreductive surgery (CRS) along with peri-operative intra
      peritoneal chemotherapy (PIC). However, most of the surgical data comes from mono
      institutional phase I or II studies and there is a broad range of variability
      regarding inclusion criteria, cytoreductive surgical procedures, drugs,
      temperatures and methods of delivering the heated chemotherapy (open vs. closed
      abdomen). This manuscript critically analyze and discuss the results of a group
      of health care providers trying to achieve a consensus statement in the
      management of this group of patients. The main conflicting points regarding
      preoperative evaluation, patient eligibility, combined treatment methodology,
      postoperative follow-up and future investigational perspectives were summarized
      as a list of multiple-choice questions. A questionnaire was placed on the website
      of the "5(th) International Workshop on Peritoneal Surface Malignancies" and the
      group members voted via internet. The results were presented for further debate
      during a dedicated session of the Workshop. The general treatment guidelines and
      future investigational perspectives were defined.

PMID- 18726891
TI  - Locoregional treatment of peritoneal carcinomatosis from gastric cancer.
AB  - The authors reviewed the natural history and the main features of the peritoneal
      carcinomatosis from gastric cancer briefly and analyzed the pertinent literature
      concerning the locoregional modalities for prevention and for treatment. Results
      of the web based voting by experts were also summarized. As regards the
      peritoneal perfusion with cytotoxic drugs with or without hyperthermia for
      preventing peritoneal carcinomatosis in high risk patients, there are some
      randomized clinical trials and one meta-analysis supporting a benefit of the
      procedure. However, disparity in methodology (drugs, dosage, duration of the
      treatment, addition of hyperthermia, etc.) precludes the adoption of a shared
      protocol to be used in the clinical practice in high risk patients. Once the
      peritoneal carcinomatosis is established, the approach reported in literature is
      the peritonectomy associated with hyperthermic perfusion. However, data
      supporting benefits are scanty, and limited to few centers with a specific
      experience in this field. With regard to the main questions addressed to the
      experts' panel and concerning the indications for treatment and methodology,
      there was a general consistency among the experts and agreement with the findings
      of the literature. The need for a large multicenter trial to confirm the benefit
      and risk of intraperitoneal chemotherapy was recognized by both the experts and
      the authors.

PMID- 18726892
TI  - Rcl is a novel ETV1/ER81 target gene upregulated in breast tumors.
AB  - ETV1 (ER81) is a transcription factor that can be activated by HER2/Neu, a proto
      oncoprotein often overexpressed in metastatic breast tumors. Here, we demonstrate
      that ETV1 downregulation suppresses proliferation of HER2/Neu-positive MDA-MB-231
      breast cancer cells in vitro and tumor formation in vivo, proving for the first
      time the existence of a critical role of ETV1 in breast cancer cell physiology. A
      screen for novel ETV1 target genes hinted at Rcl, an enzyme involved in
      nucleotide metabolism. To characterize the human Rcl gene, we cloned its promoter
      and found that ETV1 and HER2/Neu cooperated in activating the Rcl promoter,
      whereas a dominant-negative ETV1 molecule suppressed the Rcl promoter. Moreover,
      ETV1 and HER2/Neu synergized to upregulate the endogenous Rcl gene. ETV1 also
      bound to the Rcl promoter in vivo, indicating that Rcl is a bona fide target gene
      of ETV1. Hybridization of Rcl cDNA to a breast cancer array revealed that Rcl is
      overexpressed in approximately 40% of all breast tumors. Importantly, its
      expression significantly escalates with increasing tumor grade, strongly
      implicating that Rcl contributes to breast tumorigenesis. Since joint
      overexpression of Rcl with vascular endothelial growth factor, another target
      gene of ETV1, has been shown to induce tumor formation, Rcl may be one crucial
      effector of ETV1 and HER2/Neu in breast tumors. Furthermore, given its expression
      pattern and enzymatic function in nucleotide metabolism, Rcl presents itself as a
      novel target in breast cancer therapy via modulation of its activity by small
      molecule drugs.

PMID- 18726893
TI  - ERK activation and nuclear signaling induced by the loss of cell/matrix adhesion
      stimulates anchorage-independent growth of ovarian cancer cells.
AB  - Ovarian cancer metastasis involves the sloughing of epithelial cells from the
      ovary into the peritoneal cavity, where the cells can survive and proliferate in
      peritoneal ascites under anchorage-independent conditions. For normal epithelial
      cells and fibroblasts, cell adhesion to the extracellular matrix is required to
      prevent apoptosis and for proper activation and nuclear signaling of the ERK MAP
      kinase. The mechanisms of ERK regulation by adhesion have been determined by our
      lab and others. In this report, we elucidate a novel means of ERK regulation by
      cellular adhesion in ovarian cancer cells. We demonstrate that ERK and its
      activator MEK are robustly stimulated after cell detachment from a substratum in
      several ovarian cancer cell lines, but not a benign ovarian cell line,
      independent of serum and FAK or PAK activity. MEK and ERK activation was
      sustained for 48 h after detachment, while activation by serum or growth factors
      in adherent cells was transient. Re-attachment of suspended ovarian cells to
      fibronectin restored basal levels of MEK and ERK activity. ERK activity in
      suspended cells was dynamically controlled through an autocrine stimulatory
      pathway and prevalent phosphatase activity. Suspended cells demonstrated higher
      levels of ERK nuclear signaling to Elk1 compared to adherent cells. Inhibition of
      ERK activation with the MEK inhibitor U0126 had minor effects on adherent cell
      growth, but greatly decreased growth in soft agar. These data demonstrate a
      unique regulation of ERK by cellular adhesion and suggest a mechanism by which
      ERK may regulate anchorage-independent growth of metastatic ovarian cancer cells.

PMID- 18726894
TI  - Consensus statement on the loco-regional treatment of appendiceal mucinous
      neoplasms with peritoneal dissemination (pseudomyxoma peritonei).
AB  - Pseudomyxoma peritonei (PMP) is a rare condition mostly originating from low
      malignant potential mucinous tumours of the appendix. Although this disease
      process is minimally invasive and rarely causes haematogenous or lymphatic
      metastases, expectation of long-term survival are limited with no prospect of
      cure. Recently, the combined approach of cytoreductive surgery (CRS) and
      perioperative loco-regional chemotherapy (PLC) has been proposed as the standard
      of treatment for the disease. The present paper summarizes the available
      literature data and the main features of the comprehensive loco-regional
      treatment of PMP. The controversial issues concerning the indications and
      technical methodology in PMP management were discussed through a web-based voting
      system by internationally known experts. Results were presented for further
      evaluation during a dedicated session of "The Fifth International Workshop on
      Peritoneal Surface Malignancy (Milan, Italy, December 4-6, 2006)". The experts
      agreed that multiple prospective trials support a benefit of the procedure in
      terms of improved survival, as compared with historical controls. Concerning the
      main controversial methodological questions, there was an high grade of
      consistency among the experts and agreement with the findings of the literature.

PMID- 18726895
TI  - Hyperthermic intraperitoneal chemotherapy with and without cytoreductive surgery
      for epithelial ovarian cancer.
AB  - Women with epithelial ovarian cancer (EOC) usually present with advanced disease
      and overall only just over half survive 5 years. Even following a complete
      response to front-line treatment two-thirds will recur, with a resultant dismal
      prognosis. We review and discuss the role of surgery and hyperthermic
      intraperitoneal chemotherapy (HIPEC) in EOC and present the results of the ovary
      consensus panel (OCP) convened for the 5th International Workshop on Peritoneal
      Surface Malignancy.

PMID- 18726896
TI  - Expression of TSLC1, a candidate tumor suppressor gene mapped to chromosome
      11q23, is downregulated in unfavorable neuroblastoma without promoter
      hypermethylation.
AB  - Although it has been well documented that loss of human chromosome 11q is
      frequently observed in primary neuroblastomas, the smallest region of overlap
      (SRO) has not yet been precisely identified. Previously, we performed array
      comparative genomic hybridization (array-CGH) analysis for 236 primary
      neuroblastomas to search for genomic aberrations with high-resolution. In our
      study, we have identified the SRO of deletion (10-Mb or less) at 11q23. Within
      this region, there exists a TSLC1/IGSF4/CADM1 gene (Tumor suppressor in lung
      cancer 1/Immunoglobulin superfamily 4/Cell adhesion molecule 1), which has been
      identified as a putative tumor suppressor gene for lung and some other cancers.
      Consistent with previous observations, we have found that 35% of primary
      neuroblastomas harbor loss of heterozygosity (LOH) on TSLC1 locus. In contrast to
      other cancers, we could not detect the hypermethylation in its promoter region in
      primary neuroblastomas as well as neuroblastoma-derived cell lines. The
      clinicopathological analysis demonstrated that TSLC1 expression levels
      significantly correlate with stage, Shimada's pathological classification, MYCN
      amplification status, TrkA expression levels and DNA index in primary
      neuroblastomas. The immunohistochemical analysis showed that TSLC1 is remarkably
      reduced in unfavorable neuroblastomas. Furthermore, decreased expression levels
      of TSLC1 were significantly associated with a poor prognosis in 108 patients with
      neuroblastoma. Additionally, TSLC1 reduced cell proliferation in human
      neuroblastoma SH-SY5Y cells. Collectively, our present findings suggest that
      TSLC1 acts as a candidate tumor suppressor gene for neuroblastoma.

PMID- 18726898
TI  - AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and
      missense mutation significance.
AB  - Almost 90% of nephrogenic diabetes insipidus (NDI) is due to mutations in the
      arginine-vasopressin receptor 2 gene (AVPR2). We retrospectively examined all the
      published mutations/variants in AVPR2. We planned to perform a comprehensive
      review of all the AVPR2 mutations/variants and to test whether any amino acid
      change causing a missense mutation is significantly more or less common than
      others. We performed a Medline search and collected detailed information
      regarding all AVPR2 mutations and variants. We performed a frequency comparison
      between mutated and wild-type amino acids and codons. We predicted the mutation
      effect or reported it based on published in vitro studies. We also reported the
      ethnicity of each mutation/variant carrier. In summary, we identified 211 AVPR2
      mutations which cause NDI in 326 families and 21 variants which do not cause NDI
      in 71 NDI families. We described 15 different types of mutations including
      missense, frameshift, inframe deletion, deletion, insertion, nonsense,
      duplication, splicing and combined mutations. The missense mutations represent
      the 55.83% of all the NDI published families. Arginine and tyrosine are
      significantly (P = 4.07E-08 and P = 3.27E-04, respectively) the AVPR2 most
      commonly mutated amino acids. Alanine and glutamate are significantly (P = 0.009
      and P = 0.019, respectively) the least mutated AVPR2 amino acids. The spectrum of
      mutations varies from rare gene variants or polymorphisms not causing NDI to rare
      mutations causing NDI, among which arginine and tyrosine are the most common
      missense. The AVPR2 mutations are spread world-wide. Our study may serve as an
      updated review, comprehensive of all AVPR2 variants and specific gene locations.
      J. Cell. Physiol. 217: 605-617, 2008. (c) 2008 Wiley-Liss, Inc.

PMID- 18726897
TI  - Concurrent and longitudinal associations of basal and diurnal cortisol with
      mental health symptoms in early adolescence.
AB  - Recent biosocial theories postulate that both biological risk and the social
      context influence the development of mental health problems [Boyce and Ellis
      (2005) Development and Psychopathology, 17(2), 271-301]. Guided by this
      framework, we examined whether basal cortisol and its diurnal rhythm were
      associated with mental health symptoms in early adolescence. Because cross
      sectional and longitudinal investigations sometimes reveal different cortisol
      mental health associations, we examined the association both concurrently and
      longitudinally when children transition to middle school, a time which entails a
      major change in social context from single to multiple teachers, classrooms, and
      sets of classmates. Salivary cortisol was measured three times a day (waking,
      afternoon, and bedtime) across 3 days when adolescents were 5th graders. Mental
      health was measured when adolescents were in 5th and 7th grades, just before and
      after the transition to middle school. To deal with the substantial comorbidity
      of internalizing and externalizing symptoms at this developmental stage, mental
      health measures distinguished overall symptom severity from the preponderance of
      internalizing versus externalizing symptoms (i.e., directionality). A three-level
      Hierarchical Linear Model was used to extract basal cortisol and its diurnal
      rhythm separate from the day-to-day and within-the-day fluctuations in cortisol
      in response to daily experiences. Results were specific to symptom severity,
      suggesting that cortisol is a nonspecific risk factor for mental health symptoms
      in young adolescents. At 5th grade, low basal cortisol was associated with
      concurrent symptom severity. However, longitudinally, it was adolescents with
      high cortisol at 5th grade who were at risk for increasing mental health symptoms
      by 7th grade. Flat diurnal rhythms in 5th grade were related to levels of symptom
      severity at both 5th and 7th grades. Considering the change in social context, as
      defined by the transition to middle school, helped resolve seemingly inconsistent
      evidence that both hypo- and hyper-arousal were associated with mental health
      symptoms in early adolescence.

PMID- 18726899
TI  - The consensus statement on the locoregional treatment of abdominal sarcomatosis.
AB  - Abdominal sarcomatosis (AS) is a rare condition characterized by soft tissue
      sarcoma spreading throughout the abdomen, in the absence of extra-abdominal
      dissemination. Retroperitoneal sarcomas, pelvic sarcomas, particularly uterine
      leiomyosarcoma, and gastrointestinal stromal tumors (GISTs) most frequently give
      rise to AS. Systemic chemotherapy is the standard of care for AS from non-GIST
      sarcomas, but with an essentially palliative aim and major limitations.
      Innovative targeted therapies has deeply affected the natural history of GIST, at
      least in prolonging significantly survival in responsive patients. In this
      context, the notion that abdominal spread in the lack of extra-peritoneal lesions
      may typically occur in a number of patients, along with the dismal prognosis
      generally carried by AS, has prompted a few centers to perform cytoreductive
      surgery and perioperative intraperitoneal chemotherapy. To date, the rarity of
      these presentations makes it difficult to evaluate the clinical results and the
      role of combined local-regional treatment is still a matter of debate. This
      article presents the results of a group of experts from around the World trying
      to achieve a consensus statement in AS comprehensive management. A questionnaire
      was placed on the website of the 5th International Workshop on Peritoneal Surface
      Malignancy and the experts voted via internet.

PMID- 18726900
TI  - Treatment failure following complete cytoreductive surgery and perioperative
      intraperitoneal chemotherapy for peritoneal dissemination from colorectal or
      appendiceal mucinous neoplasms.
AB  - BACKGROUND: Peritonectomy combined with perioperative intraperitoneal
      chemotherapy is a successful treatment option for patients with peritoneal
      dissemination of appendiceal and colorectal malignancy. Despite its efficacy,
      recurrences remain a common problem. METHODS: Patients with peritoneal
      dissemination from appendiceal or colorectal malignancy who underwent complete
      cytoreduction and perioperative intraperitoneal chemotherapy were included in
      this study. Data regarding recurrent disease found on abdominal exploration
      and/or diagnostic studies was extracted from a prospective database and analyzed.
      RESULTS: Seventy patients with colorectal cancer carcinomatosis and 402 with
      appendiceal neoplasm were analyzed. Forty-nine of 70 and 111 of 402 patients
      developed documented recurrences. The median survival of 49 patients with
      colorectal cancer was 33 months while the median survival for patients with
      appendiceal neoplasms was not reached. The most common type of recurrent disease
      was a localized intra-abdominal recurrence for both appendiceal and colon cancer
      patients. Patients who underwent second surgery for recurrent disease had an
      improved survival. CONCLUSION: Additional treatments should be strongly
      considered in patients who fail an initial cytoreduction combined with
      perioperative intraperitoneal chemotherapy. This resulted in 5-year survival in
      17% of colorectal patients and 70% of the appendiceal mucinous neoplasm patients.

PMID- 18726903
TI  - Quality of life and nutritional assessment in peritoneal surface malignancy
      (PSM): recommendations for care.
AB  - Quality of life (QOL) and nutritional status of patients treated for peritoneal
      surface malignancy are important areas for ongoing assessment. A working group of
      clinicians including a dietitian, physicians, and quality of life researchers was
      formed as part of the Fifth International Workshop on Peritoneal Surface
      Malignancy. The purpose of the group was to form a consensus statement on both
      quality of life and nutritional assessment in PSM. The relevant literature from
      the quality of life and nutritional assessment in peritoneal surface malignancy
      was reviewed and integrated to form a consensus statement. Baseline and ongoing
      assessment of both quality of life and nutritional status of patients undergoing
      cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) is
      recommended.

PMID- 18726901
TI  - Hepsin colocalizes with desmosomes and induces progression of ovarian cancer in a
      mouse model.
AB  - Hepsin is a serine protease that is widely expressed in different tissues and
      cell types, most prominently in the normal liver and kidney. Overexpression of
      hepsin has been associated with prostate cancers, ovarian cancers and renal cell
      carcinomas. The physiological functions of hepsin in normal tissues and tumors
      are poorly understood. To gain insight into its function in ovarian cancer, we
      analyzed the expression and subcellular localization of hepsin protein in ovarian
      cancer cell lines and tumors. We showed that the membrane-associated hepsin
      protein is present at desmosomal junctions, where it colocalizes with its
      putative proteolytic substrate hepatocyte growth factor. Consistent with the
      growing evidence that desmosomal junctions and their constituents play a role in
      cancer progression, we demonstrated that overexpression of hepsin promotes
      ovarian tumor growth in a mouse model. The ability of ectopic hepsin to induce
      tumor growth in mice is abrogated by the mutation of 3 critical residues in the
      catalytic domain, thus implicating the enzymatic activity of hepsin in promoting
      tumor progression.

PMID- 18726906
TI  - Building on a consensus.

PMID- 18726905
TI  - Characterization of the transcriptional regulation of the regulator of G protein
      signaling 2 (RGS2) gene during 3T3-L1 preadipocyte differentiation.
AB  - Adipocyte differentiation is a complex process involving several signaling
      pathways. Molecular mechanisms regulating the very early stage of adipocyte
      differentiation is not fully appreciated yet. Several inducible genes at the
      early stage of preadipocyte differentiation have been identified, including the
      regulator of G protein signaling 2 (RGS2), a member of the RGS protein
      superfamily. This study aimed to clarify the precise induction profile of RGS2
      and to determine the essential transcription element(s) regulating RGS2
      expression in differentiating 3T3-L1 preadipocytes. RGS2 mRNA expression was
      elevated immediately at 1 h after differentiation initiation and it remained high
      until the late stage of differentiation. The putative promoter sequence
      (approximately 3,000 bp) of the mouse RGS2 gene was isolated and the RGS2
      promoter activity was significantly upregulated 3 h after inducing
      differentiation. The primary signaling pathway leading to RGS2 transcriptional
      activation appeared to be cAMP-dependent. Sequential deletion and site-directed
      mutagenesis strategies demonstrate that the RGS2 promoter sequence truncated down
      to 78 bp in size retained full inducibility by the differentiation stimuli.
      Mutation of a Sp1 site within the 78 bp region significantly blocked promoter
      activity. In addition, high expression of Sp1 transcription factor was noted
      prior to and paralleling the differentiation process. Taken together, our data
      suggest that RGS2 transcription is immediately induced via a cAMP-dependent
      pathway after initiation of 3T3-L1 differentiation and the RGS2 mRNA level
      remains consistently high throughout the differentiation progression. A Sp1 site
      within RGS2 promoter appeared to be a crucial response element to regulate RGS2
      transcription.

PMID- 18726904
TI  - Response to mercaptopurine for refractory autoimmune cytopenias in children.
AB  - BACKGROUND: Several treatment strategies are available for children with severe
      immune thrombocytopenic purpura (ITP) and other immune cytopenias refractory to
      initial therapies. 6-Mercaptopurine (6MP) is one option, however it has not been
      well studied in children, especially as a single agent, and no pediatric case
      series have been reported since 1970. PATIENTS AND METHODS: We reviewed the
      experience at our institution over 8 years, using 6MP as a steroid sparing
      treatment for children with ITP, auto-immune hemolytic anemia (AIHA) or Evans
      syndrome. A total of 29 pediatric patients were treated with 6MP from 2000 to
      2007. RESULTS: Response was defined as a rise in hemoglobin by at least 1.5 g/dl
      and to a level of 10 g/dl or greater in patients treated for anemia, or a
      platelet count >or=50 x 10(9)/L in patients treated for thrombocytopenia. We
      found an overall response rate of 83% among all patients. Fourteen percent of
      patients stopped drug because of side effects. CONCLUSIONS: These results suggest
      that 6MP can be an effective single-agent treatment for refractory immune
      cytopenias in children. Prospective studies are warranted to determine long-term
      efficacy and toxicity and to more clearly define patient populations most likely
      to respond.

PMID- 18726907
TI  - The Delphi approach to Attain consensus in methodology of local regional therapy
      for peritoneal surface malignancy.
AB  - At the Fifth International Workshop on Peritoneal Surface Malignancy (PSM), held
      in Milan, December 2006, the consensus on technical aspects of cytoreductive
      surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) was obtained
      through the Delphi process. The following topics were discussed: pre-operative
      workup; eligibility to CRS + HIPEC; intra-operative staging system; technical
      aspects of surgery; residual disease classification systems; HIPEC: nomenclature
      and modalities; drugs, carrier solution and optimal temperature; morbidity
      grading systems. Conflicting points regarding above-mentioned topics were
      elaborated and voted in two rounds by a panel of international experts in local
      regional therapy. The purpose of this manuscript is to describe the organization
      and the methodology of the consensus statements and to interpret and discuss the
      implications of the most striking results.

PMID- 18726909
TI  - Independent component analysis as a model-free approach for the detection of BOLD
      changes related to epileptic spikes: a simulation study.
AB  - EEG-fMRI in epileptic patients is commonly analyzed using the general linear
      model (GLM), which assumes a known hemodynamic response function (HRF) to
      epileptic spikes in the EEG. In contrast, independent component analysis (ICA)
      can extract Blood-Oxygenation Level Dependent (BOLD) responses without imposing
      constraints on the HRF. This technique was evaluated on data generated by
      superimposing artificial responses on real background fMRI signals. Simulations
      were run using a wide range of EEG spiking rates, HRF amplitudes, and activation
      regions. The data were decomposed by spatial ICA into independent components. A
      deconvolution method then identified component time courses significantly related
      to the simulated spikes, without constraining the shape of the HRF. Components
      matching the simulated activation regions ("concordant components") were found in
      84.4% of simulations, while components at discordant locations were found in
      12.2% of simulations. These false activations were often related to large
      artifacts that coincidentally occurred simultaneously with some of the random
      simulated spikes. The performance of the method depended closely on the
      simulation parameters; when the number of spikes was low, concordant components
      could only be identified when HRF amplitudes were large. Although ICA did not
      depend on the shape of the HRF, data processed with the GLM did not reveal the
      appropriate activation region when the HRF varied slightly from the canonical
      shape used in the model. ICA may thus be able to extract BOLD responses from EEG
      fMRI data in epileptic patients, in a way that is robust to uncertainty and
      variability in the shape of the HRF.

PMID- 18726908
TI  - Single dose of a dopamine agonist impairs reinforcement learning in humans:
      evidence from event-related potentials and computational modeling of striatal
      cortical function.
AB  - Animal findings have highlighted the modulatory role of phasic dopamine (DA)
      signaling in incentive learning, particularly in the acquisition of reward
      related behavior. In humans, these processes remain largely unknown. In a recent
      study, we demonstrated that a single low dose of a D2/D3 agonist (pramipexole)
      assumed to activate DA autoreceptors and thus reduce phasic DA bursts-impaired
      reward learning in healthy subjects performing a probabilistic reward task. The
      purpose of this study was to extend these behavioral findings using event-related
      potentials and computational modeling. Compared with the placebo group,
      participants receiving pramipexole showed increased feedback-related negativity
      to probabilistic rewards and decreased activation in dorsal anterior cingulate
      regions previously implicated in integrating reinforcement history over time.
      Additionally, findings of blunted reward learning in participants receiving
      pramipexole were simulated by reduced presynaptic DA signaling in response to
      reward in a neural network model of striatal-cortical function. These preliminary
      findings offer important insights on the role of phasic DA signals on
      reinforcement learning in humans and provide initial evidence regarding the
      spatiotemporal dynamics of brain mechanisms underlying these processes.

PMID- 18726910
TI  - Neural correlates of personally familiar faces: parents, partner and own faces.
AB  - Investigations of the neural correlates of face recognition have typically used
      old/new paradigms where subjects learn to recognize new faces or identify famous
      faces. Familiar faces, however, include one's own face, partner's and parents'
      faces. Using event-related fMRI, we examined the neural correlates of these
      personally familiar faces. Ten participants were presented with photographs of
      own, partner, parents, famous and unfamiliar faces and responded to a distinct
      target. Whole brain, two regions of interest (fusiform gyrus and cingulate
      gyrus), and multiple linear regression analyses were conducted. Compared with
      baseline, all familiar faces activated the fusiform gyrus; own faces also
      activated occipital regions and the precuneus; partner faces activated similar
      areas, but in addition, the parahippocampal gyrus, middle superior temporal gyri
      and middle frontal gyrus. Compared with unfamiliar faces, only personally
      familiar faces activated the cingulate gyrus and the extent of activation varied
      with face category. Partner faces also activated the insula, amygdala and
      thalamus. Regions of interest analyses and laterality indices showed anatomical
      distinctions of processing the personally familiar faces within the fusiform and
      cingulate gyri. Famous faces were right lateralized whereas personally familiar
      faces, particularly partner and own faces, elicited bilateral activations.
      Regression analyses show experiential predictors modulated with neural activity
      related to own and partner faces. Thus, personally familiar faces activated the
      core visual areas and extended frontal regions, related to semantic and person
      knowledge and the extent and areas of activation varied with face type.

PMID- 18726911
TI  - Pseudohomophone effects provide evidence of early lexico-phonological processing
      in visual word recognition.
AB  - Previous research using event-related brain potentials (ERPs) suggested that
      phonological processing in visual word recognition occurs rather late, typically
      after semantic or syntactic processing. Here, we show that phonological
      activation in visual word recognition can be observed much earlier. Using a
      lexical decision task, we show that ERPs to pseudohomophones (PsHs) (e.g., ROZE)
      differed from well-matched spelling controls (e.g., ROFE) as early as 150 ms
      (P150) after stimulus onset. The PsH effect occurred as early as the word
      frequency effect suggesting that phonological activation occurs early enough to
      influence lexical access. Low-resolution electromagnetic tomography analysis
      (LORETA) revealed that left temporoparietal and right frontotemporal areas are
      the likely brain regions associated with the processing of phonological
      information at the lexical level. Altogether, the results show that phonological
      processes are activated early in visual word recognition and play an important
      role in lexical access.

PMID- 18726912
TI  - The atRA-responsive gene neuron navigator 2 functions in neurite outgrowth and
      axonal elongation.
AB  - Neuron navigator 2 (Nav2) was first identified as an all-trans retinoic acid
      (atRA)-responsive gene in human neuroblastoma cells (retinoic acid-induced in
      neuroblastoma 1, RAINB1) that extend neurites after exposure to atRA. It is
      structurally related to the Caenorhabditis elegans unc-53 gene that is required
      for cell migration and axonal outgrowth. To gain insight into NAV2 function, the
      full-length human protein was expressed in C. elegans unc-53 mutants under the
      control of a mechanosensory neuron promoter. Transgene expression of NAV2 rescued
      the defects in unc-53 mutant mechanosensory neuron elongation, indicating that
      Nav2 is an ortholog of unc-53. Using a loss-of-function approach, we also show
      that Nav2 induction is essential for atRA to induce neurite outgrowth in SH-SY5Y
      cells. The NAV2 protein is located both in the cell body and along the length of
      the growing neurites of SH-SY5Y cells in a pattern that closely mimics that of
      neurofilament and microtubule proteins. Transfection of Nav2 deletion constructs
      in Cos-1 cells reveals a region of the protein (aa 837-1065) that directs
      localization with the microtubule cytoskeleton. Collectively, this work supports
      a role for NAV2 in neurite outgrowth and axonal elongation and suggests this
      protein may act by facilitating interactions between microtubules and other
      proteins such as neurofilaments that are key players in the formation and
      stability of growing neurites.

PMID- 18726913
TI  - Neuronal and glial alterations in the cerebellar cortex of maternally deprived
      rats: gender differences and modulatory effects of two inhibitors of
      endocannabinoid inactivation.
AB  - Adult animals submitted to a single prolonged episode of maternal deprivation
      (MD) [24 h, postnatal day 9-10] show behavioral alterations that resemble
      specific symptoms of schizophrenia. Accordingly, this experimental procedure has
      been proposed as an animal model of schizophrenia based on the neurodevelopmental
      hypothesis. We have recently reported that MD-induced sex-dependent alterations
      in the hippocampus of neonatal rats. In view of recent evidence for important
      implications of the cerebellum in neurodevelopmental psychiatric diseases, we
      have now addressed possible degenerative changes in the cerebellar cortex of
      neonatal Wistar rats of both genders. To evaluate the presence of degenerated
      nerve cells, we used Fluoro-Jade C staining and for the study of astrocytes, we
      employed glial fibrillary acidic protein. Further, we analyzed the modulatory
      actions of two inhibitors of endocannabinoids inactivation, the fatty acid amide
      hydrolase inhibitor N-arachidonoyl-serotonin, AA-5-HT, and the endocannabinoid
      reuptake inhibitor, OMDM-2 (daily subcutaneous injections during the postnatal
      period 7-12). The animals were sacrificed at postnatal Day 13. MD induced
      significant increases in the number of Fluoro-Jade C positive cells (indicative
      of degenerating neurons) and in the number of glial fibrillary acidic protein
      positive cells, only in males. The two cannabinoid compounds reversed or
      attenuated these effects. The present results provide new insights regarding the
      psychopathological implications of the cerebellum, the role of the
      endocannabinoid system in neural development, and the possible neurodevelopmental
      basis of gender differences in schizophrenia.

PMID- 18726915
TI  - Electrocommunication signals alone are sufficient to increase neurogenesis in the
      brain of adult electric fish, Apteronotus leptorhynchus.
AB  - Social interaction can have profound influences on the structure of the adult
      brain, but little is known about the precise stimulus feature found within social
      interaction that induces such brain plasticity. We examined the effects of social
      stimuli on cell addition and radial glial fiber formation in the brains of adult
      electric fish. These fish communicate primarily through weak, quasi-sinusoidal
      electric signals. Fish were housed in isolation, paired with another fish or
      exposed to only the electrocommunication signals of another fish for 7 days.
      After 3 days of exposure to these stimulus conditions, fish were injected with
      bromodeoxyuridine (BrdU) to mark newborn cells. We sacrificed the fish 4 days
      after BrdU injection and used immunohistochemistry to measure cell addition
      (BrdU+), the fraction of added cells that differentiated into neurons
      (BrdU+/NeuroTrace+) and the density of radial glia fibers (vimentin+) in the
      periventricular zone of the diencephalon. Fish that were exposed only to the
      electrocommunication signals of another fish and no other social stimuli had
      equivalent levels of cell addition and radial glial fiber density to fish that
      were housed with full social interaction and higher levels than fish housed in
      isolation. About 60% of the added cells differentiated into neurons; this
      fraction did not differ among treatment groups. Artificial sine wave electrical
      stimuli that mimicked electrocommunication signals were ineffective in increasing
      cell addition and glia fiber formation above those found in isolated fish. Thus,
      stimuli through a single modality are sufficient for inducing this brain
      plasticity, but the waveform or dynamic features of communication signals are
      crucial for the effect.

PMID- 18726916
TI  - Recurrence of Ewing sarcomas of the chest wall.
AB  - BACKGROUND: Ewing sarcomas (ES) of the chest wall are rare. Local recurrences
      occur in approximately 20% of these patients; however literature on this topic is
      scarce. Our aim was to analyze the influence of the extent of surgical resection
      on outcome, and to find positive prognostic factors for survival. PROCEDURE: A
      retrospective analysis of all patients who were under 18 and treated between 1977
      and 2006 for Ewing sarcoma of the chest wall was performed. RESULTS: Twenty-seven
      patients with ES were diagnosed at our institution; 14 males and 13 females.
      Twenty-three patients underwent local resection, which was complete in 13. Nine
      patients had a wide resection, including more ribs than just the affected one.
      Complete remission (CR) was achieved in 14/27 patients. Recurrence was observed
      in 13 patients: local recurrence (LR) and distant metastasis (DM) both in 7. One
      of the patients had both LR and DM. All patients with LR and two patients with DM
      only died of disease. Overall survival after 10 and 20 years was 73% and 47%,
      respectively. Complete resection, wide resection, gender, or age were no
      significant factors affecting outcome. CONCLUSIONS: Relapse carries a high
      mortality risk and none of the patients with LR eventually survived. Wide
      resection of at least a complete normal adjacent rib above and below the thoracic
      wall tumor as a fixed rule seems unnecessary.

PMID- 18726914
TI  - Identification of prostaglandin E2 receptors mediating perinatal masculinization
      of adult sex behavior and neuroanatomical correlates.
AB  - Prostaglandin E2 (PGE2) mediates the organization of male rat sexual behavior and
      medial preoptic area (MPOA) neuroanatomy during a sensitive perinatal window.
      PGE2 is up-regulated in response to estradiol, and initiates a two-fold increase
      in dendritic spines densities on neurons. All the four receptors for PGE2 and EP1
      4 are present in developing POA, a critical region controlling male sexual
      behavior. Previous studies explored that EP receptors are involved in PGE2
      induction of neonatal levels of spinophilin protein, a surrogate marker for
      dendritic spine formation, but did not assess behavioral masculinization. Here,
      we used two approaches, suppression of EP receptor expression with antisense
      oligonucleotides and activation of EP receptors with selective agonists, to test
      which receptors are necessary and sufficient, respectively, for the effects of
      PGE2 on behavior and neuronal morphology. In female rats, neonatal treatment with
      antisense oligonucleotides against EP2 or EP4 but not EP1 or EP3 completely
      prevented the expression of adult behavior organized by PGE2 exposure. The
      effects of ONO-DI-004, ONO-AE-259-01, ONO-AE-248, and ONO-AE1-329 (EP1-4 agonists
      respectively) were equivalent to PGE2 treatment, which suggests activating any EP
      receptor neonatally suffices in masculinizing sex behavior. When given alone, not
      all EP agonists increased neonatal POA spinophilin levels; yet giving each
      agonist neonatally increased adult levels. Moreover, adult spinophilin levels
      significantly correlated with two measures of male sexual behavior. The body of
      evidence suggests that EP2 and EP4 are both necessary and sufficient for PGE2
      induced masculinization of sex behavior, whereas EP1 and EP3 provide redundant
      roles.

PMID- 18726917
TI  - Transient myelodysplastic syndrome in X-linked agammaglobulinemia with a novel
      Btk mutation.
AB  - X-linked agammaglobulinemia (XLA) is a rare disorder in which recurrent
      infections occur due to low serum globulins and circulating B lymphocytes caused
      by a mutation in the Bruton tyrosine kinase (Btk) gene. While myelodysplastic
      syndrome (MDS) associated with low B lymphocyte counts has been described, clonal
      cytogenetic abnormalities in confirmed cases of XLA have never been reported. We
      describe a case of XLA with a novel Btk mutation who also had a persistent clonal
      population in the bone marrow with abnormal cytogenetics in multiple chromosomes
      that resolved 1(1/2) years after treatment with IVIG, mimicking a picture of
      transient MDS.

PMID- 18726918
TI  - Relative red blood cell enzyme levels as a clue to the diagnosis of pyruvate
      kinase deficiency.
AB  - Evaluation of two patients with transfusion dependent anemia revealed RBC
      pyruvate kinase to be 33% and 41% of the mean normal value, with normal or high
      values of other RBC enzymes. Parental PK activities were just below normal in
      three of four of the parents. Subsequent DNA analysis revealed both patients to
      be compound heterozygotes for PKLR gene mutations, two of which are previously
      undescribed. Borderline low pyruvate kinase activities with increased in other
      RBC enzyme activities should prompt consideration of measurement of parental
      enzyme activities, and confirmation by DNA analysis if available.

PMID- 18726919
TI  - Octreotide therapy in asparaginase-associated pancreatitis in childhood acute
      lymphoblastic leukemia.
AB  - Little is known about octreotide therapy in asparaginase-associated pancreatitis
      (AAP) in children. Of the 59 children with acute lymphoblastic leukemia (ALL)
      receiving E. coli L-asparaginase, 5 patients (8.5%) developed AAP. Octreotide was
      administered to four patients. Clinical and laboratory improvement were evident
      after octreotide therapy. There were no deaths and no severe adverse side effects
      were noted. No pseudocysts were detected; however, two of the four patients
      developed diabetes. One child without octreotide treatment developed chronic
      pancreatitis and pseudocyst. We conclude that octreotide therapy appears to be
      safe and potentially beneficial in the management of AAP in children.

PMID- 18726920
TI  - Risk prediction of fever in neutropenia in children with cancer: a step towards
      individually tailored supportive therapy?
AB  - BACKGROUND: Fever in severe chemotherapy-induced neutropenia (FN) is the most
      frequent manifestation of a potentially lethal complication of current intensive
      chemotherapy regimens. This study aimed at establishing models predicting the
      risk of FN, and of FN with bacteremia, in pediatric cancer patients. METHODS: In
      a single-centre cohort study, characteristics potentially associated with FN and
      episodes of FN were retrospectively extracted from charts. Poisson regression
      accounting for chemotherapy exposure time was used for analysis. Prediction
      models were constructed based on a derivation set of two thirds of observations,
      and validated based on the remaining third of observations. RESULTS: In 360
      pediatric cancer patients diagnosed and treated for a cumulative chemotherapy
      exposure time of 424 years, 629 FN were recorded (1.48 FN per patient per year,
      95% confidence interval (CI), 1.37-1.61), 145 of them with bacteremia (23% of FN;
      0.34; 0.29-0.40). More intensive chemotherapy, shorter time since diagnosis, bone
      marrow involvement, central venous access device (CVAD), and prior FN were
      significantly and independently associated with a higher risk to develop both FN
      and FN with bacteremia. The prediction models explained more than 30% of the
      respective risks. CONCLUSIONS: The two models predicting FN and FN with
      bacteremia were based on five easily accessible clinical variables. Before
      clinical application, they need to be validated by prospective studies.

PMID- 18726922
TI  - Immigrants and the use of preventive care in the United States.
AB  - Using data from the Medical Expenditure Panel Survey, we compare immigrants' use
      of preventive care with that of natives. We employ a multinomial switching
      regression framework that accounts for non-random selection into continuous
      private insurance, temporary private insurance, public insurance, and no
      insurance. Our results indicate that among the populations with continuous
      private coverage and without coverage (uninsured), immigrants, especially non
      citizens, are less likely to use preventive care than natives. We find that the
      longer immigrants stay in the US the more their use of care approximates to that
      of natives. However, for most types of care, immigrants' use of care never fully
      converges to that of natives. Among the publicly insured population, immigrants'
      use of care is similar to natives, but non-citizen immigrants are significantly
      less likely to use preventive measures. We find that the ability to speak English
      does not have a significant effect on the use of preventive care among publicly
      insured persons.

PMID- 18726921
TI  - High level of mitogen-activated protein kinase phosphatase-1 expression is
      associated with cisplatin resistance in osteosarcoma.
AB  - BACKGROUND: Cisplatin is one of the most effective chemotherapeutic agents in the
      treatment of several solid tumors including osteosarcoma (OS). Despite aggressive
      treatment, 25% of patients with OS continue to die from their disease. Since
      cisplatin based regimens have been uniformly used in OS therapy, treatment
      failure is likely due, at least in part, to cisplatin resistance. PROCEDURE: The
      objective of this study was to determine the relationship between MKP-1
      expression and cisplatin sensitivity of OS cell lines and to explore the
      mechanism underlying this relationship. Three OS cell lines were examined for
      their MKP-1 expression and cisplatin sensitivity. JNK phosphorylation and
      apoptosis induction was also measured. Western and Northern blot, flow cytometry,
      siRNA, and MTT assays were used. RESULTS: U2OS cells, which express high level of
      MKP-1, are less sensitive to cisplatin-induced cell death. Inhibition of MKP-1 by
      siRNA silencing sensitizes U2OS cells to cisplatin-induced cell death.
      Furthermore, delayed apoptosis induction following cisplatin treatment was
      observed in U2OS, in parallel to decreased JNK activation, increased MKP-1
      expression and relatively increased cisplatin resistance. Interestingly,
      triptolide, an MKP-1 inhibitor, blocks MKP-1 expression and enhances cisplatin
      induced cell death. CONCLUSION: High MKP-1 expression is associated with
      decreased sensitivity or increased resistance to cisplatin-induced cell death in
      OS cell lines, and MKP-1 could potentially be used as a marker of cisplatin
      resistance and a therapeutic target for molecular therapies.

PMID- 18726923
TI  - Role of musculature during defecation in a particle-feeding arachnid,
      Archegozetes longisetosus (Acari, Oribatida).
AB  - Most extant Chelicerata are characterized by external digestion and the ingestion
      of fluid food. Exceptions include the marine taxa, most Opiliones, and the mite
      groups Opilioacarida (Parasitiformes) and Sarcoptiformes (Acariformes), which
      ingest particulate food. This leads to different physiological and morphological
      adaptations for food processing, including the production and extrusion of solid
      fecal pellets, which are rather large in sarcoptiform mites. Few studies have
      investigated the defecation of such large fecal pellets, and available
      information is contradictory. We use a combination of non invasive microscopical
      techniques and in vivo examination to investigate the complex functional
      morphology of the anal region of the oribatid mite Archegozetes longisetosus
      Aoki. The opening of the anus is at least initiated by indirect muscular action
      via an increase of hemolymph pressure, through the action of dorsoventral muscles
      (dvm). Extrusion of the fecal pellet is accomplished by the prerectal muscle
      collar, with full opening of the anus and rotation and bowing of the plates
      probably resulting from pressure of the pellet. The sequential nature of these
      actions was demonstrated by many observations in which the anus opened only
      partially; these were concomitant with dmv contraction but pellets were not being
      extruded. All muscles directly connected to the anal and adanal regions assist in
      keeping the anus closed; they are antagonists to hydrostatic forces that are
      necessary for normal activity. Based on the literature, no obvious similarities
      were noted with defecation musculature in other particle-feeding chelicerates,
      but most muscles can be homologized with those of more specialized oribatid
      mites. The function of the outer anal muscles has been modified in both
      Euphthiracaridae and Brachypylina to assist in providing general hemolymph
      pressure.

PMID- 18726924
TI  - CAPE (caffeic acid phenethyl ester)-based propolis extract (Bio 30) suppresses
      the growth of human neurofibromatosis (NF) tumor xenografts in mice.
AB  - Dysfunction of the NF1 gene coding a RAS GAP is the major cause of
      neurofibromatosis type 1 (NF1), whereas neurofibromatosis type 2 (NF2) is caused
      primarily by dysfunction of the NF2 gene product called merlin that inhibits
      directly PAK1, an oncogenic Rac/CDC42-dependent Ser/Thr kinase. It was
      demonstrated previously that PAK1 is essential for the growth of both NF1 and NF2
      tumors. Thus, several anti-PAK1 drugs, including FK228 and CEP-1347, are being
      developed for the treatment of NF tumors. However, so far no effective NF
      therapeutic is available on the market. Since propolis, a very safe healthcare
      product from bee hives, contains anticancer ingredients called CAPE (caffeic acid
      phenethyl ester) or ARC (artepillin C), depending on the source, both of which
      block the oncogenic PAK1 signaling pathways, its potential therapeutic effect on
      NF tumors was explored in vivo. Here it is demonstrated that Bio 30, a CAPE-rich
      water-miscible extract of New Zealand (NZ) propolis suppressed completely the
      growth of a human NF1 cancer called MPNST (malignant peripheral nerve sheath
      tumor) and caused an almost complete regression of human NF2 tumor (Schwannoma),
      both grafted in nude mice. Although CAPE alone has never been used clinically,
      due to its poor bioavailability/water-solubility, Bio 30 contains plenty of
      lipids which solubilize CAPE, and also includes several other anticancer
      ingredients that seem to act synergistically with CAPE. Thus, it would be worth
      testing clinically to see if Bio 30 and other CAPE-rich propolis are useful for
      the treatment of NF patients.

PMID- 18726925
TI  - Screening for trisomy 18 by maternal age, fetal nuchal translucency, free beta
      human chorionic gonadotropin and pregnancy-associated plasma protein-A.
AB  - OBJECTIVES: To derive a model and examine the performance of first-trimester
      screening for trisomy 18 by maternal age, fetal nuchal translucency (NT)
      thickness, and maternal serum free beta-human chorionic gonadotropin (beta-hCG)
      and pregnancy-associated plasma protein-A (PAPP-A). METHODS: Prospective combined
      screening for trisomy 21 was performed at 11 + 0 to 13 + 6 weeks in 56 893
      singleton pregnancies, including 56 376 cases of euploid fetuses, 395 with
      trisomy 21 and 122 with trisomy 18. The measured free beta-hCG and PAPP-A were
      converted into a multiple of the median (MoM) and then into likelihood ratios
      (LR). Similarly, the measured NT was transformed into LRs using the mixture model
      of NT distributions. In each case the LRs for NT and the biochemical markers were
      multiplied by the age and gestation-related risk to derive the risk for trisomy
      21 and trisomy 18. Detection rates (DRs) and false-positive rates (FPRs) were
      calculated by taking the proportions with risks above a given risk threshold.
      RESULTS: In screening with the algorithm for trisomy 21, at a FPR of 3%, the
      estimated DRs of trisomies 21 and 18 were 89% and 82%, respectively. The use of
      an algorithm for trisomy 18 identified 93% of affected fetuses at a FPR of 0.2%.
      When the algorithm for trisomy 21 was used and screen positivity was fixed at a
      FPR of 3%, and in addition the algorithm for trisomy 18 was used and screen
      positivity was fixed at a FPR of 0.2%, the overall FPR was 3.1% and the DRs of
      trisomies 21 and 18 were 90% and 97%, respectively. CONCLUSIONS: A beneficial
      side effect of first-trimester combined screening for trisomy 21 is the detection
      of a high proportion of fetuses with trisomy 18. If an algorithm for trisomy 18
      in addition to the one for trisomy 21 is used, more than 95% of trisomy 18
      fetuses can be detected with a minor increase of 0.1% in the overall FPR.

PMID- 18726926
TI  - Narrative change in psychotherapy: differences between good and bad outcome cases
      in cognitive, narrative, and prescriptive therapies.
AB  - This study aimed to clarify the relationship between changes in the patients'
      narratives and therapeutic outcomes. Two patients were selected from three
      psychotherapeutic models (cognitive, narrative, and prescriptive therapies), one
      with good therapeutic outcome and the other with bad therapeutic outcome.
      Sessions from the initial, middle, and final phases for each patient were
      evaluated in terms of narrative structural coherence, process complexity, and
      content diversity. Differences between patients' total narrative production were
      found at the end of the therapeutic process. Good outcome cases presented a
      higher statistically significant total narrative change than poor outcome cases.

PMID- 18726927
TI  - Ultrasonographic anatomy of perineal structures during pregnancy and immediately
      following obstetric injury.
AB  - OBJECTIVES: To assess perineal anatomy using ultrasound before and immediately
      after delivery. METHODS: Structures in the perineum were studied by real-time two
      dimensional transvaginal and endoanal ultrasound imaging using a combined linear
      and semicircular (up to 200 degrees sector) probe. We examined 45 nulliparous
      pregnant women and 44 primiparae immediately after delivery (40 with anal
      sphincter tears and four without sphincter injury). In each case a single
      longitudinal image was later assessed by two observers in order to evaluate
      interobserver agreement. RESULTS: In pregnancy, the perineal membrane,
      puboperineal muscles, conjoined longitudinal muscle and central point were
      identified on real-time examination in 91%, 98%, 100% and 100% of cases,
      respectively. At offline evaluation of the longitudinal images obtained for each
      of the pregnant women, the percentage of cases in which each structure was
      identified by both observers ranged from 64% to 100%. In the women who were
      examined postpartum, all structures were identified by both observers in all four
      of the women without sphincter injury. In the women with sphincter tears, the
      perineal membrane, puboperineal muscles, conjoined longitudinal muscle and
      central point were found by ultrasound to be intact in 10%, 10%, 55% and 18%,
      respectively. The agreement between two observers regarding identification of
      intact structures in a single longitudinal image was good for perineal membrane
      (kappa index, 0.66), fair for puboperineal muscles (kappa index, 0.40), and poor
      for conjoined longitudinal muscle and central point (kappa index, 0.08 and 0.17,
      respectively). CONCLUSIONS: Ultrasonography might be helpful in the evaluation of
      perineal anatomy and extent of perineal tears. However, the relatively poor
      agreement between the two observers evaluating single linear transvaginal images
      implies that both transverse and longitudinal projections are necessary to obtain
      relevant information. Further studies are needed regarding the importance of
      specific sonographically identified structures and their role in pelvic floor
      dysfunction after delivery.

PMID- 18726928
TI  - Intrauterine programming of the cardiovascular system.

PMID- 18726929
TI  - Three-dimensional power Doppler derived vascular indices: what are we measuring
      and how are we doing it?

PMID- 18726931
TI  - FOXL2 mutations and genomic rearrangements in BPES.
AB  - The FOXL2 gene is one of 10 forkhead genes, the mutations of which lead to human
      developmental disorders, often with ocular manifestations. Mutations in FOXL2 are
      known to cause blepharophimosis syndrome (BPES), an autosomal dominant eyelid
      malformation associated (type I) or not (type II) with ovarian dysfunction,
      leading to premature ovarian failure (POF). In addition, a few mutations have
      been described in patients with isolated POF. Here, we review all currently
      described FOXL2 sequence variations and genomic rearrangements in BPES and POF.
      Using a combined mutation detection approach, it is possible to identify the
      underlying genetic defect in a major proportion (88%) of typical BPES patients.
      Of all genetic defects found in our BPES cohort, intragenic mutations represent
      81%. They include missense changes, frameshift and nonsense mutations, in-frame
      deletions, and duplications, that are distributed along the single-exon gene.
      Genomic rearrangements comprising both deletions encompassing FOXL2 and deletions
      located outside its transcription unit, represent 12% and 5% of all genetic
      defects in our BPES cohort, respectively. One of the challenges of genetic
      testing in BPES is the establishment of genotype-phenotype correlations, mainly
      with respect to the ovarian phenotype. Genetic testing should be performed in the
      context of genetic counseling, however, and should be systematically complemented
      by a multidisciplinary clinical follow-up. Another challenge for health care
      professionals involved in BPES is the treatment of the eyelid phenotype and the
      prevention or treatment of POF.

PMID- 18726932
TI  - Evaluation of the effect of machine settings on quantitative three-dimensional
      power Doppler angiography: an in-vitro flow phantom experiment.
AB  - OBJECTIVES: Three-dimensional (3D) ultrasound is being used increasingly to
      acquire and subsequently quantify power Doppler data within the clinical setting.
      One proprietary software package calculates three 3D vascular indices: the
      vascularization index (VI), the flow index (FI), and the vascularization flow
      index (VFI). Our aim was to evaluate how different settings affect the Doppler
      signal in terms of its quantification by these three indices within a 3D dataset.
      METHODS: A computer-driven 'flow phantom' was used to continuously pump a nylon
      particle-based blood mimic (Orgasol(trade mark)) around a closed system through a
      C-flex(trade mark) tube embedded in an agar-based tissue mimic. The test tanks
      were insonated with a modified 3D transvaginal 4-8-MHz ultrasound transducer
      (V530D) and power Doppler data were acquired over a series of different settings.
      Each experiment involved the manipulation of just one Doppler setting in order to
      study it in isolation. RESULTS: As expected, all of the power Doppler settings,
      when altered, were found to effect significant changes (P < 0.05) in the VI, FI
      and VFI. The gain and signal power had the greatest effect, producing no Doppler
      signals at the lowest settings and the highest recordable indices at the maximum
      settings. The pulse repetition frequency (PRF) was the next most influential
      setting but a Doppler signal was seen and measurable at all of the different
      settings. The other Doppler settings had a much less profound effect on the
      vascular indices, with subtle but significantly different measures across the
      full range of settings. The speed of data acquisition was also found to affect
      the vascular indices, all of which were reduced when the fast mode was used
      although the only significant effect was on the VFI. CONCLUSIONS: The VI, FI and
      VFI are all affected significantly by variations in power Doppler settings and by
      the speed of acquisition. The gain and signal power have the greatest effect on
      the power Doppler signal, followed closely by the PRF. The other settings and
      speed of acquisition also influence the signal, but to a much lesser degree. It
      is essential to maintain Doppler settings if any meaningful comparisons are to be
      made within and between subjects.

PMID- 18726933
TI  - Prenatal diagnosis of partial lumbar asoma by two- and three-dimensional
      ultrasound and computed tomography: embryological aspects and perinatal
      management.
AB  - Asoma is an unusual type of hemivertebra distinct from lateral hemivertebra in
      its underlying mechanisms, its rarity, its often isolated nature and the high
      risk of it causing medullary compression. We report a case of isolated partial
      agenesis of a vertebral body (asoma) diagnosed at 23 weeks' gestation by
      ultrasonography, in a fetus showing hyperkyphosis with vertebral canal
      disruption. The diagnosis was established using ultrasound and computed
      tomography, which allowed measurement of the angle of kyphosis and helped in the
      determination of the postnatal orthopedic prognosis. In our patient, prenatal
      diagnosis of asoma facilitated optimization of postnatal management and reduced
      the neonate's risk of developing paralysis. The main anatomical parameters in the
      determination of the orthopedic risk are the level of the anomaly, the angle of
      kyphosis and the degree of vertebral canal disruption.

PMID- 18726934
TI  - Sonographic findings of uterine sacculation during pregnancy.

PMID- 18726935
TI  - Evaluation of volume vascularization index and flow index: a phantom study.
AB  - OBJECTIVES: Three-dimensional (3D) power Doppler ultrasonography provides indices
      to quantify moving blood within a volume of interest (e.g. ovary, endometrium,
      tumor or placenta). The purpose of this study was to determine the influence of
      ultrasound instrument settings on vascularization index (VI) and flow index (FI)
      at different flow velocities, using a specially built flow phantom with a small
      tube diameter. METHODS: Blood-mimicking fluid was pumped at 10-100 mL/h through a
      plastic tube with a diameter of 0.65 mm within a virtual spherical volume
      (content 137.12 cm(3)) of a Voluson 730 Expert 3D power Doppler ultrasound
      instrument. VI and FI were determined at different pulse repetition frequency
      (PRF) settings, with minimal and maximal wall motion filter (WMF) settings. The
      measured VI was compared with the actual VI. RESULTS: The ability to measure VI
      and FI at different flow velocities was highly dependent on the PRF and WMF
      settings. In our experimental set-up, using a PRF of 0.3 kHz, flow velocities of
      about 2 cm/s and higher could be registered. Measured VI was overestimated up to
      44 times relative to actual VI. CONCLUSIONS: Our main finding in a laboratory set
      up was a considerable overestimation of moving blood volume using 3D power
      Doppler ultrasound in a single small tube. The degree of overestimation depends
      on the spatial resolution and on the settings of the ultrasound instrument. When
      small vessels are involved in a clinical setting, interpretation of VI should
      take this overestimation of moving blood volume into account.

PMID- 18726937
TI  - Life course theory as a framework to examine becoming a mother of a medically
      fragile preterm infant.
AB  - Life course theory, a sociological framework, was used to analyze the phenomenon
      of becoming a mother, with longitudinal narrative data from 34 women who gave
      birth prematurely after a high-risk pregnancy, and whose infant became medically
      fragile. Women faced challenges of mistimed birth and mothering a technologically
      dependent infant. Before social ties were established, legal and biological ties
      required mothers to make critical decisions about their infants. Liminality
      characterized mothers' early involvement with their infants. The mothers worked
      to know, love, and establish deeper attachments to this baby. The infant's
      homecoming was a key turning point; it decreased liminality of early mothering,
      increased mothers' control of infants' care, and gave them time and place to know
      their infants more intimately.

PMID- 18726938
TI  - Three-dimensional ultrasound of the urethral sphincter predicts continence
      surgery outcome.
AB  - AIM: To assess the predictive value of three-dimensional (3D) ultrasound volumes
      of the urethral sphincter in women undergoing continence surgery. MATERIALS AND
      METHODS: Women with urodynamic stress incontinence undergoing to Burch
      colposuspension were prospectively studied using videocystourethrography (VCU),
      urethral pressure profilometry (UPP) and a 3D transvaginal ultrasound scan of the
      urethra. The total urethral sphincter volume, urethral volume, maximum cross
      sectional area, and rhabdosphincter volume were calculated, preoperatively.
      Surgical outcome was assessed at 6 months using VCU. Urethral function parameters
      were correlated to surgical outcomes using the Mann-Whitney U-test. RESULTS:
      Ninety-one women were studied. Women who failed continence surgery had
      significantly smaller preoperative urethral sphincter volumes than those who had
      an objective cure (P < 0.001). UPP parameters were not found to be predictive of
      surgical outcome (P = 0.5). CONCLUSIONS: The assessment of the urethral sphincter
      using a 3D ultrasound scan predicts the outcome of continence surgery.

PMID- 18726939
TI  - Clean intermittent self-catheterization: a burden for the patient?
AB  - AIM: To assess patients' perception of clean intermittent self-catheterization
      (CISC) for voiding dysfunction. PATIENTS AND METHODS: A total of 101 patients
      performing CISC because of voiding dysfunction were invited to participate in
      this questionnaire survey. The response rate was 91% (92/101). RESULTS: The mean
      time over which CISC was performed was 5 years (standard deviation (SD) +/- 6.3)
      and the mean frequency of CISC per day was three times (SD +/- 2). Almost 80%
      (72/92) of the patients perceived CISC as easy or very easy and CISC did not
      interfere at all or interfered a little bit with work or other regular daily
      activities in more than 80% (76/92). Almost 90% (80/92) reported no or minimal
      pain while performing CISC. This did not interfere at all or interfered a little
      bit with work or other regular daily activities in almost 90% (80/92). Quality of
      life improved considerably due to CISC in more than 60% (56/92) and 12% (11/92)
      complained of a deterioration. In multivariable analysis, severe pain performing
      CISC (odds ratio 20.9, 95% confidence interval 1.7-259.9, P = 0.018) was the only
      factor that predicted poor quality of life. CONCLUSIONS: The majority of patients
      considered CISC to be an easy and painless procedure which did not interfere with
      daily activities. Consequently, quality of life improved in more than 60% of the
      patients. Therefore, CISC does not appear to be a burden for the patient and,
      from a patient's perspective, can be recommended.

PMID- 18726941
TI  - Carotid artery stent placement is safe in the very elderly (> or =80 years).
AB  - BACKGROUND: Carotid artery stent (CAS) placement is an alternative to carotid
      endarterectomy (CEA) for stroke prevention. Clinical adoption of CAS depends on
      its safety and efficacy compared to CEA. There are conflicting reports in the
      literature regarding the safety of CAS in the elderly. To address these safety
      concerns, we report our single-center 13-year CAS experience in very elderly (>
      or =80 years of age) patients. METHODS: Between 1994 and 2007, 816 CAS procedures
      were performed at the Ochsner Clinic Foundation. Very elderly patients, those >
      or =80 years of age, accounted for 126 (15%) of all CAS procedures. Independent
      neurologic examination was performed before and after the CAS procedure. RESULTS:
      The average patient age was 82.9 +/- 2.9 years. Almost one-half (44%) were women
      and 40% were symptomatic from their carotid stenoses. One-third of the elderly
      patients met anatomic criteria for high surgical risk as their indication for
      CAS. The procedural success rate was 100% with embolic protection devices used in
      50%. The 30-day major adverse coronary or cerebral events (MACCE) rate was 2.7%
      (n = 3) with all events occurring in the symptomatic patient group [death = 0.9%
      (n = 1), myocardial infarction = 0%, major (disabling) stroke = 0.9% (n = 1), and
      minor stroke = 0.9% (n = 1)]. CONCLUSION: Elderly patients, > or =80 years of
      age, may undergo successful CAS with a very low adverse event rate as determined
      by an independent neurological examination. We believe that careful case
      selection and experienced operators were keys to our success.

PMID- 18726940
TI  - Activation of hepatic stellate cells after phagocytosis of lymphocytes: A novel
      pathway of fibrogenesis.
AB  - Increased CD8-T lymphocytes and reduced natural killer (NK) cells contribute to
      hepatic fibrosis. We have characterized pathways regulating the interactions of
      human hepatic stellate cells (HSCs) with specific lymphocyte subsets in vivo and
      in vitro. Fluorescence-activated cell sorting (FACS) was used to characterize
      human peripheral blood lymphocytes (PBLs) and intrahepatic lymphocytes (IHLs)
      obtained from healthy controls and from patients with either hepatitis B virus
      (HBV) or hepatitis C virus (HCV) with advanced fibrosis. Liver sections were
      analyzed by immunohistochemistry and confocal microscopy. To investigate in vitro
      interactions, PBLs from healthy controls or patients with HCV cirrhosis were co
      cultured with an immortalized human HSC line (LX2 cells) or with primary HSCs.
      Significant alterations in lymphocyte distribution were identified in IHLs but
      not PBLs. The hepatic CD4/CD8 ratio and NK cells were significantly reduced in
      HBV/HCV patients. Expression of alpha-smooth muscle actin and infiltration of
      CD4, CD8, and NK cells were readily apparent in liver sections from patients with
      cirrhosis but not in healthy controls. Lymphocytes from each subset were in
      proximity to HSCs primarily within the periportal regions, and some were directly
      attached or engulfed. In culture, HSC activation was stimulated by HCV-derived
      CD8-subsets but attenuated by NK cells. Confocal microscopy identified lymphocyte
      phagocytosis within HSCs that was completely prevented by blocking intracellular
      adhesion molecule 1 (ICAM-1) and integrin molecules, or by irradiation of HSCs.
      LX2 knockdown of either Cdc42 or Rac1 [members of the Rho-guanosine
      triphosphatase (GTPase) family] prevented both phagocytosis and the activation of
      HSC by HCV-derived lymphocytes. CONCLUSION: The CD4/CD8 ratio and NK cells are
      significantly decreased in livers with advanced human fibrosis. Moreover, disease
      associated but not healthy lymphocytes are engulfed by cultured HSCs, which is
      mediated by the Rac1 and Cdc42 pathways. Ingestion of lymphocytes by HSCs in
      hepatic fibrosis is a novel and potentially important pathway regulating the
      impact of lymphocytes on the course of hepatic fibrosis.

PMID- 18726942
TI  - Assignment of the absolute configuration of zwitterionic and neutral
      macropodumines by means of TDDFT CD calculations.
AB  - Macropodumines B and C (1, 2) are fused pentacyclic alkaloids previously isolated
      from the Chinese medicinal plant Daphniphyllum macropodum. Macropodumine B (1)
      possesses an amazing structural feature of a cyclopentadienyl carbanion,
      stabilized as a zwitterion by an internal iminium cation, which was confirmed by
      X-ray diffraction analysis. On the basis of the X-ray geometry, the absolute
      configuration of 1 was determined by employing the solid-state CD/TDDFT approach.
      The absolute configuration of 2 was instead determined by using TDDFT CD
      calculations on DFT-optimized geometries, in comparison with CD spectra recorded
      in solution.

PMID- 18726943
TI  - Tetralogy of Fallot: evaluation by 4D spatiotemporal image correlation.

PMID- 18726944
TI  - Structure determination of chiral sulfoxide in diastereomeric bicalutamide
      derivatives.
AB  - We report on the synthesis and investigation of two diastereomers (5a and 5b) of
      a new bicalutamide analog with an asymmetric carbon atom and a chiral sulfoxide
      group. These bicalutamide analogs are novel androgen receptor antagonists with
      biological activities that depend significantly on the configuration of their
      stereogenic centers. We determined the absolute configuration at the SO center by
      combining X-ray and NMR measurements with quantum chemical calculations. Since 5a
      and 5b failed to yield satisfactory crystals for X-ray crystal structure
      determination, analogs 6a and 6b differing in only one remote functional group
      relative to the chiral sulfoxide were synthesized, which yielded satisfactory
      crystals. X-ray structure determination of 6a and 6b provided the absolute
      configuration at the chiral sulfoxide. Since the structural difference between 5
      and 6 is remote from the chiral sulfoxide, the structural assignment was extended
      from the diastereomers of 6 to those of 5 provisionally. These assignments were
      verified with the help of measured and DFT-calculated proton and carbon NMR
      chemical shifts.

PMID- 18726945
TI  - Configurationally driven folding of model tetrapeptides containing L- or D
      morpholine-3-carboxylic acids as beta-turn nucleators.
AB  - The conformational analysis by NMR, IR, and molecular modeling of tetrapeptides
      containing morpholine-3-carboxylic acid (Mor) as a proline surrogate is
      presented. The relationship between the chirality of the cyclic amino acid at
      position i+1 and the turn propensity is maintained with respect to the reference
      proline-containing peptides, although marked differences in the type of folded
      structures were observed. The conformational profile of morpholine-containing
      turn peptides as a function of the chirality of the cyclic amino acid indicated
      that the heterochiral tetrapeptide containing the D-isomer of the cyclic amino
      acid is more prone to nucleate compact folded structures, although with no
      resemblance to the beta-turn structures of D-proline-containing peptides. Also,
      the solvation system proved to influence the organization of folded structures,
      as in the more interactive CD(3)CN the model peptides showed more compact
      conformations. The L-Mor-containing peptide displayed two rotamers at the Val-Mor
      amide bond. The trans isomer did not experience any turn structures, nor any
      intramolecular hydrogen-bonds, whereas the cis isomer showed a strong preference
      for a type VI beta-turn structure, thus providing a different conformational
      asset with respect to the beta-turn structure as reported for the reference L
      proline model peptide.

PMID- 18726946
TI  - Is low bladder compliance predictive of detrusor overactivity?
AB  - AIMS: Bladder compliance (BC) expresses the relationship between bladder volume
      and bladder pressure and is generally regarded as a measure of bladder stiffness
      or distensibility. Many types of voiding dysfunction have been associated with
      low BC such as detrusor overactivity (DO). It has previously been reported that
      the presence of DO is an independent predictor of low BC. The aim of this study
      was to assess the predictive value of low BC for the diagnosis of idiopathic DO
      using ambulatory urodynamics as the gold standard investigation for comparison.
      METHODS: All patients with LUTS attending a single center for both conventional
      and ambulatory urodynamics over a 5-year period were reviewed. The predictive
      value of various set levels of BC was compared using a receiver-operator
      characteristics (ROC) curve in an attempt to find the optimal threshold of BC for
      the diagnosis of DO. RESULTS: 162 patients were identified and following
      exclusions 143 (88%) data sets were suitable for analysis. The mean (s.d.) BC in
      the 99 patients with DO was 92 (80) ml/cm H(2)O compared to 112 (91) ml/cm H(2)O
      in those who did not show DO on ambulatory urodynamics. This difference was not
      statistically significant according to a non-parametric Mann-Whitney test (P =
      0.22). Furthermore no set threshold of BC was able to provide sufficient accuracy
      for the diagnosis of DO. The area under the curve was less than 0.5 (0.47)
      indicating a level of accuracy less than "chance". CONCLUSIONS: Low bladder
      compliance is not predictive of DO in our series. It is imperative to note that
      our results are obtained from a cohort comprising predominantly female patients
      without BOO and is therefore different to previous reports concentrating on male
      patients with BOO.

PMID- 18726947
TI  - Desmopressin, as a "designer-drug," in the treatment of overactive bladder
      syndrome.
AB  - AIMS: This study looked at whether oral desmopressin, by decreasing kidney urine
      production, would prolong bladder filling-time thereby increasing the time to
      reach maximum capacity, thus reducing overactive bladder (OAB) symptoms, and
      providing an alternative method of treatment to OAB sufferers. METHODS: An
      investigator-initiated, 2-week, multi-national, multi-centre, "proof-of-concept,"
      phase IIb, double-blind, placebo-controlled, prospective, randomized, cross-over
      study was conducted using 0.2 mg of oral desmopressin in adults suffering with
      OAB. Patients were included in the trial period if they had >or=4 voids in the
      first 8-hr of the day after rising, excluding the first morning void. The primary
      endpoint was evaluation of effectiveness of desmopressin in increasing the time
      to the first OAB symptom episodes during the first 8-hr following treatment.
      RESULTS: Time to first void was 8-min later on the drug than on placebo (P =
      0.27). However, the drug led to one less void (3.2 vs. 4.2) in the same period (P
      < 0.001). There was an increase in the time to first urgency episode with a
      decrease in the number of urgency episodes in the drug days compared to placebo
      (P < 0.003). There was a subjective improvement in frequency and urgency and
      overall quality-of-life as measured by the ICIQ-OAB. Twenty-seven people reported
      adverse events which were all mild, headache being the commonest and no
      hyponatremia was recorded. CONCLUSIONS: Antidiuresis, using oral desmopressin
      tablets, is a novel, feasible and safe (short-term basis) method of treatment for
      adults with OAB, and could be considered in the armamentarium of drugs available
      for the treatment of OAB.

PMID- 18726948
TI  - Is there a relationship between glomerular filtration rate and detrusor
      overactivity in women?
AB  - AIMS: The relationship of detrusor overactivity (DO) to neuromuscular causes is
      well established, but a connection to kidney function has not yet been studied.
      We sought to evaluate whether patients with DO have differences in estimated
      glomerular filtration rate (eGFR). METHODS: After Institutional Review Board
      approval, we collected data from all patients who underwent urodynamic testing in
      our office from September 1, 2006 to February 28, 2007 and calculated eGFR using
      the equation derived from the Modification of Diet in Renal Disease (MDRD) study.
      RESULTS: Data were collected on 359 patients, who had a mean eGFR for all
      patients of 82.99 ml/min/1.73 m(2) (+/-22.2). The patients were divided into
      groups by the presence or absence of DO on filling cystometry. There was no
      significant difference in eGFR between the patients with and without DO (80.9
      ml/min/1.73 m(2) vs. 84.4, P = 0.290). CONCLUSIONS: Kidney function does not
      differ between patients with or without DO.

PMID- 18726949
TI  - Patient reported and anatomical outcomes after surgery for pelvic organ prolapse.
AB  - AIM: Primary aim was to modify Pelvic Floor Distress Inventory (PFDI) and Pelvic
      Floor Impact Questionnaire (PFIQ) to assess pelvic organ prolapse (POP) in Arabic
      Muslim women. Secondary aim was to compare functional and anatomical outcomes of
      POP repair. METHODS: Questionnaire. A characteristic (prayer) was added to PFIQ.
      Linguistic validation of questionnaires was then done. Twenty cases were enrolled
      in a pilot study to test internal consistency and reliability. Subsequent study.
      Prospective study included women with symptomatic POP >or= stage II. History,
      examination by POP-Q, and administration of PFDI and PFIQ, were done before and 6
      months after surgery. RESULTS: Questionnaire. Internal consistency of added
      question was good (Cronbach alpha = 0.78). Test-retest reliability of individual
      PFIQ items was variable. Subsequent Study. Between September 2004 and February
      2007, 78 consecutive women were included. Cystocele, rectocele, and no site
      predominated in 74.4%, 17.9% and 7.7% of cases, respectively. Preoperatively
      19.2%, 15.4% and 47.4% reported stress, urge, and mixed incontinence,
      respectively. Overall and individual urinary symptoms scores improved
      significantly after surgery. There were significant improvements in individual
      symptoms of constipation, splint to defecate and losing not well formed stools.
      Low self-esteem was most negative impact of prolapse on quality of life (QoL)
      followed by prayer. After surgery 90% of subjects had anatomical cure. After
      surgery, QoL issues are significantly related to anatomic location of prolapse as
      determined by POP-Q. CONCLUSIONS: Modified PFIQ and PFDI are suitable to assess
      POP among Muslim women. Postoperatively, many prolapse-related symptoms and QoL
      significantly improve after surgery on the short term with an anatomic cure rate
      of 90%.

PMID- 18726950
TI  - Targeting prostate cancer for focal destruction: can we find it?

PMID- 18726951
TI  - Utility of extended pattern prostate biopsies for tumor localization: pathologic
      correlations after radical prostatectomy.
AB  - BACKGROUND: Focal targeted therapy has been proposed as a potential treatment for
      localized prostate cancer in an attempt to reduce morbidity. However, these
      modalities rely heavily on accurate tumor localization to achieve total tumor
      ablation. In the current study, we sought to examine the ability of contemporary
      extended pattern prostate biopsy to predict the location of tumors. METHODS: A
      total of 281 men with prostate cancer detected via a standardized extended
      pattern biopsy template with at least 12 cores and who subsequently underwent
      radical prostatectomy were evaluated. Tumor location on biopsy, stratified by
      laterality and by site (apex vs mid-base prostate), was compared with
      corresponding locations on the prostatectomy specimen. Generalized estimating
      equation models were developed to assess the effects of clinical variables on
      pathologic agreement between biopsy and prostatectomy specimens. RESULTS: Of the
      281 prostate biopsies, the positive predictive value (PPV) of right and left
      needle biopsy was high at 97.3% and 96.7%, respectively. However, the negative
      predictive value (NPV) was low at 24.7% and 31.3%, respectively. When more
      specific locations were considered, the NPV improved at the apex. However, this
      came at a cost to the PPV. Tumor focality on prostatectomy specimen was the only
      clinical feature found to be significantly and consistently related to pathologic
      agreement. CONCLUSIONS: Contemporary extended pattern prostate biopsy, although
      able to diagnose cancers, fails to provide reliable localization of tumors to
      specific areas of the prostate. Focal therapy, which relies heavily on
      localization, should only be performed with this caveat in mind.

PMID- 18726952
TI  - Rare mutations of FGFR2 causing apert syndrome: identification of the first
      partial gene deletion, and an Alu element insertion from a new subfamily.
AB  - Apert syndrome (AS) is a severe disorder, characterized by craniosynostosis and
      complex syndactyly of the hands and feet. Two heterozygous gain-of-function
      substitutions (Ser252Trp and Pro253Arg) in exon IIIa of fibroblast growth factor
      receptor 2 (FGFR2) are responsible for >98% of cases. Here we describe two novel
      mutations in FGFR2 in the two patients in whom a mutation had not previously been
      found in our cohort of 227 AS cases. The first is a 1.93-kb deletion, removing
      exon IIIc and substantial portions of the flanking introns. This is the first
      large FGFR2 deletion described in any individual with craniosynostosis. The other
      mutation is a 5' truncated Alu insertion into exon IIIc. This is the third Alu
      insertion identified in AS; all have occurred within an interval of only 104 bp,
      representing an enrichment of over a million-fold compared to the background
      genomic rate. We show that the inserted Alu element belongs to a small subfamily,
      not previously known to be mobile, which we term Alu Yk13. Both the deletion and
      insertion are likely to act by a similar gain-of-function mechanism in which
      disruption of exon IIIc leads to illegitimate mesenchymal expression of an FGFR2
      spliceform containing the alternatively spliced exon IIIb. All the AS-associated
      Alu insertions have arisen in the paternal germline; we propose that their
      enrichment in FGFR2 is driven by positive selection of the mutant spermatogonial
      progenitors, a mechanism analogous to that explaining why the canonical AS
      nucleotide substitutions also reach exceptionally high levels in sperm.

PMID- 18726953
TI  - Surface markers for the murine oval cell response.
AB  - The biology of progenitor activation in the liver is of considerable medical and
      scientific interest. The powerful genetic tools available for the mouse make it
      an ideal model system to study this complex process involving many different cell
      types. However, reagents for the isolation and study of distinct hepatic
      subpopulations have been quite limited compared to those available for
      hematopoietic cells. To produce cell surface reactive reagents more specific for
      the oval cell response, we generated a new collection of monoclonal antibodies by
      immunization of Fischer rats with enzymatically dispersed nonparenchymal cells
      from the livers of adult mice treated with 3,5-diethoxycarbonyl-1,4
      dihydrocollidine. Each of the resulting antibodies recognized a surface antigen
      present on a liver cell subset and permitted the viable isolation of the
      associated subpopulation by fluorescence-activated cell sorting. Differential
      activity was observed on normal liver cells and at different stages of oval cell
      activation, indicating potential utility for progenitor cell identification. The
      subdivision of liver cells using these tools should facilitate the study of the
      biology of ductal and periductal hepatic cell types, including progenitors.
      CONCLUSION: A new panel of surface reactive monoclonal antibodies to support
      investigation of the murine oval cell response has been developed.

PMID- 18726954
TI  - Carotid artery stenting in elderly patients: importance of case selection.
AB  - OBJECTIVES: This study was conducted to determine if carotid stenting (CS) could
      be safely performed in the elderly. BACKGROUND: Age has been shown to be a
      predictor of neurological complications during CS. We postulated that CS could be
      safely performed in elderly patients if certain anatomical and clinical markers
      such as excessive vascular tortuosity, heavy concentric calcification of the
      lesion, and decreased cerebral reserve were avoided. METHODS: From July 2003 to
      October 2007, 142 patients aged > or =50% or asymptomatic stenosis > or =70%. All
      patients underwent carotid and cerebral angiography to determine anatomic
      suitability and stent risk. Demographic and outcome data were entered into a
      database; other data were obtained retrospectively. Independent neurology
      evaluation was performed before and at 24 hr after the procedure. RESULTS: The
      mean age was 83.2 years, 62% were male, 25.5% were symptomatic, 8.5% had
      postcarotid endarterectomy restenosis, and 6.0% had contralateral internal
      carotid artery occlusion. There were no intracranial hemorrhages or
      periprocedural myocardial infarctions. One patient had amaurosis fugax. There
      were two minor and three major strokes in-hospital (3.3%). All patients had 30
      day follow-up. One of the major strokes expired. Thus the overall 30-day stroke
      or death rate was 3.3% and major stroke or death rate was 2.0%. The 30-day stroke
      or death rate was 5.1% for symptomatic patients and 2.6% for asymptomatic
      patients. CONCLUSION: CS can be performed safely in anatomically suitable elderly
      patients with low adverse event rates. CS should remain a revascularization
      option in appropriately selected elderly patients.

PMID- 18726955
TI  - Treatment of acute limb ischemia with a percutaneous mechanical thrombectomy
      based endovascular approach: 5-year limb salvage and survival results from a
      single center series.
AB  - OBJECTIVES: The study evaluated long-term limb salvage and survival of an
      endovascular approach that incorporates mechanical thrombectomy (PMT) in the
      management of arterial thrombosis. BACKGROUND: Acute limb ischemia is associated
      with a high risk of amputation and death. Previous reports from the United States
      (U.S.) of surgical and nonsurgical treatments are limited to primarily 30 days to
      1 year. METHODS: Single-center, retrospective review of 57 consecutive patients
      (30 male, 27 female; mean age 63.8 +/- 13.8 years) treated for limb threatening
      ischemia due to thrombotic arterial occlusions. Data includes baseline
      assessments, procedural outcomes, in-hospital complications, 30-day, and long
      term follow-up. RESULTS: Ninety-three percent of patients (n = 53) presented with
      onset of symptoms (<14 days). Angiography following PMT showed thrombus removal
      complete/substantial 36 (63.6%), partial 16 (28.0%), and minimal 5 (8.8%),
      respectively. Catheter-directed thrombolysis was used after PMT in 18 patients
      (31.6%). In-hospital success with limb salvage was attained in 96.5% (n = 55)
      with mortality of 3.5% (n = 2). Thirty-day limb salvage and mortality were 94.7%
      (n = 54) and 5.3% (n = 3), respectively. At mean 5-year follow-up (mean = 62
      months), three patients have been lost to follow-up. The results of 54/57 (94.7%)
      are available. Amputation free survival was 94.7% (n = 36/38) with long-term
      mortality rate of 29.6% (n = 16/54). CONCLUSIONS: Acute limb ischemia treated
      with PMT alone or in combination with thrombolysis, followed by definitive
      therapy, results in favorable long-term limb salvage. Allowing for appreciable
      long-term mortality in vascular patients, survivors demonstrate amputation-free
      success from the initial endovascular procedure with low reintervention rate.

PMID- 18726956
TI  - Prevention of radial artery occlusion-patent hemostasis evaluation trial (PROPHET
      study): a randomized comparison of traditional versus patency documented
      hemostasis after transradial catheterization.
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy of hemostasis
      with patency in avoiding radial artery occlusion after transradial
      catheterization. BACKGROUND: Radial artery occlusion is an infrequent but
      discouraging complication of transradial access. It is related to factors such as
      sheath to artery ratio and is less common in patients receiving heparin. Despite
      being clinically silent in most cases, it limits future transradial access.
      PATIENTS AND METHODS: Four hundred thirty-six consecutive patients undergoing
      transradial catheterization were prospectively enrolled in the study. Two hundred
      nineteen patients were randomized to group I, and underwent conventional pressure
      application for hemostasis. Two hundred seventeen patients were randomized to
      group II and underwent pressure application confirming radial artery patency
      using Barbeau's test. Radial artery patency was studied at 24 hr and 30 days
      using Barbeau's test. RESULTS: Thirty-eight patients had evidence of radial
      artery occlusion at 24 hr. Twenty patients had persistent evidence of radial
      artery occlusion at 1 month. Group II, with documented patency during hemostatic
      compression, had a statistically and clinically lower incidence of radial artery
      occlusion (59% decrease at 24 hr and 75% decrease at 30 days, P < 0.05), compared
      with patients in group I. Low body weight patients were at significantly higher
      risk of radial artery occlusion. No procedural variables were found to be
      associated with radial artery occlusion. CONCLUSION: Patent hemostasis is highly
      effective in reducing radial artery occlusion after radial access and guided
      compression should be performed to maintain radial artery patency at the time of
      hemostasis, to prevent future radial artery occlusion.

PMID- 18726957
TI  - Usefulness of subcutaneous nitrate for radial access.
AB  - OBJECTIVES: We made the hypothesis that adjunction of nitrate to lidocaine for
      local anesthesia may facilitate accessibility of radial access. BACKGROUND:
      Transradial approach is associated with a clear decrease in the rate of access
      bleeding when compared with femoral approach. The diffusion of this technique
      remains limited due to the small size and the spastic profile of this artery.
      METHODS: Eighty-four consecutive patients undergoing coronary procedures using
      radial approach were randomly assigned between two types of local anesthesia
      (double blind): 5 ml lidocaine (group L)-5 ml lidocaine + 0.5 mg dinitrate
      isosorbide (group LN). The primary endpoint was the duration of radial puncture
      (from beginning of local anesthesia to sheath insertion) and the total number of
      punctures. RESULTS: Sixty-two men and 22 women (mean age 59 +/- 8 y.o.) were
      included. Mean +/- SEM access duration was 3:33 +/- 3:11 min in group L when
      compared with 2:26 +/- 1:20 min in group LN (P < 0.05). Mean number of puncture
      was 1.50 +/- 1.0 in group L when compared with 1.16 +/- 0.5 in group LN (P =
      0.05). There were no differences between two groups concerning pain score during
      anesthesia and sheath insertion. There was no difference between two groups
      concerning the rate of hypotensive and vagal reactions. Radial spasm occurred in
      four patients in group L and only one in the group LN. CONCLUSION: Local
      anesthesia using lidocaine plus nitrate is feasible and improves the
      accessibility of radial access.

PMID- 18726959
TI  - Aldehyde-alcohol dehydrogenase and/or thiolase overexpression coupled with CoA
      transferase downregulation lead to higher alcohol titers and selectivity in
      Clostridium acetobutylicum fermentations.
AB  - Metabolic engineering (ME) of Clostridium acetobutylicum has led to increased
      solvent (butanol, acetone, and ethanol) production and solvent tolerance, thus
      demonstrating that further efforts have the potential to create strains of
      industrial importance. With recently developed ME tools, it is now possible to
      combine genetic modifications and thus implement more advanced ME strategies. We
      have previously shown that antisense RNA (asRNA)-based downregulation of CoA
      transferase (CoAT, the first enzyme in the acetone-formation pathway) results in
      increased butanol to acetone selectivity, but overall reduced butanol yields and
      titers. In this study the alcohol/aldehyde dehydrogenase (aad) gene (encoding the
      bifunctional protein AAD responsible for butanol and ethanol production from
      butyryl-CoA and acetyl-CoA, respectively) was expressed from the
      phosphotransbutyrylase (ptb) promoter to enhance butanol formation and
      selectivity, while CoAT downregulation was used to minimize acetone production.
      This led to early production of high alcohol (butanol plus ethanol) titers,
      overall solvent titers of 30 g/L, and a higher alcohol/acetone ratio. Metabolic
      flux analysis revealed the likely depletion of butyryl-CoA. In order to increase
      then the flux towards butyryl-CoA, we examined the impact of thiolase (THL, thl)
      overexpression. THL converts acetyl-CoA to acetoacetyl-CoA, the first step of the
      pathway from acetyl-CoA to butyryl-CoA, and thus, combining thl overexpression
      with aad overexpression decreased, as expected, acetate and ethanol production
      while increasing acetone and butyrate formation. thl overexpression in strains
      with asRNA CoAT downregulation did not significantly alter product formation thus
      suggesting that a more complex metabolic engineering strategy is necessary to
      enhance the intracellular butyryl-CoA pool and reduce the acetyl-CoA pool in
      order to achieve improved butanol titers and selectivity.

PMID- 18726958
TI  - Significant gene expression differences in histologically "Normal" liver
      biopsies: Implications for control tissue.
AB  - Gene expression technologies allow the analysis of gene networks whose expression
      is associated with specific pathological conditions compared with normal tissue.
      We hypothesized that histologically normal tissue obtained in different ways
      (percutaneous or surgical liver biopsies), usually used as normal controls in
      gene expression studies, could have different gene expression patterns. Group A
      comprised percutaneous liver biopsies in 14 patients with mildly elevated alanine
      aminotransferase in whom all causes of liver disease had been ruled out. Group B
      comprised 14 surgical liver biopsies of nontumoral livers. All 28 specimens were
      histologically normal. Real-time quantitative reverse-transcription polymerase
      chain reaction were used to compare the messenger RNA expression of 240 selected
      genes in these two groups. Expression of 26 of the 240 genes was significantly
      different between groups A and B; 23 genes were up-regulated in group A, while
      three were down-regulated in group B. The most notable changes occurred in the
      inflammatory response family genes. Eight genes discriminated perfectly between
      groups A and B: seven up-regulated genes (PAI1, THBS1, IL8, PTGS2, CXCR4, JUN,
      and FOS), and one down-regulated gene (IHH). In chronic hepatitis C liver
      samples, a lower or higher expression of a IL8 was found depending on whether the
      controls were obtained percutaneously or surgically. CONCLUSION: Our study
      demonstrates that histologically normal liver tissue obtained in two different
      ways (percutaneous or surgical) has different gene expression patterns
      emphasizing the importance of an adequate selection of histologically normal
      controls to prevent discordant results in gene expression studies.

PMID- 18726960
TI  - Sterilization of ginseng using a high pressure CO2 at moderate temperatures.
AB  - The aim of this study was to determine the feasibility of using high pressure CO2
      for sterilization of Ginseng powder, as an alternative method to conventional
      techniques such as gamma-irradiation and ethylene oxide. The Ginseng sample used
      in this study was originally contaminated with fungi and 5 x 10(7) bacteria/g
      that was not suitable for oral use. This is the first time that high pressure CO2
      has been used for the sterilization of herbal medicine to decrease the total
      aerobic microbial count (TAMC) and fungi. The effect of the process duration,
      operating pressure, temperature, and amount of additives on the sterilization
      efficiency of high pressure CO2 were investigated. The process duration was
      varied over 15 h; the pressure between 100 and 200 bar and the temperature
      between 25 and 75 degrees C. A 2.67-log reduction of bacteria in the Ginseng
      sample was achieved after long treatment time of 15 h at 60 degrees C and 100
      bar, when using neat carbon dioxide. However, the addition of a small quantity of
      water/ethanol/H2O2 mixture, as low as 0.02 mL of each additive/g Ginseng powder,
      was sufficient for complete inactivation of fungi within 6 h at 60 degrees C and
      100 bar. At these conditions the bacterial count was decreased from 5 x 10(7) to
      2.0 x 10(3) TAMC/g complying with the TGA standard for orally ingested products.
      A 4.3 log reduction in bacteria was achieved at 150 bar and 30 degrees C,
      decreasing the TAMC in Ginseng sample to 2,000, below the allowable limit.
      However, fungi still remained in the sample. The complete inactivation of both
      bacteria and fungi was achieved within 2 h at 30 degrees C and 170 bar using 0.1
      mL of each additive/g Ginseng. Microbial inactivation at this low temperature
      opens an avenue for the sterilization of many thermally labile pharmaceutical and
      food products that may involve sensitive compounds to gamma-radiation and
      chemically reactive antiseptic agents.

PMID- 18726962
TI  - Comparative transcriptome analysis to unveil genes affecting recombinant protein
      productivity in mammalian cells.
AB  - Low temperature culture (33 degrees C) has been shown to enhance the specific
      productivity of recombinant antibodies in Chinese hamster ovary (CHO) cells but
      did not affect antibody productivity in hybridoma (MAK) cells. We probed the
      transcriptional response of both cells undergoing temperature shift using cDNA
      microarrays. Among the orthologous gene probes, common trends in the expression
      changes between CHO and MAK are not prominent. Instead, many transcriptional
      changes were specific to only one cell line. Notably, oxidative phosphorylation
      and ribosomal genes were downregulated in MAK but not in CHO. Conversely, several
      protein trafficking genes and cytoskeleton elements were upregulated in CHO but
      remained unchanged in MAK. Interestingly, at 33 degrees C, immunoglobulin heavy
      and light chain showed no significant changes in CHO, but the immunoglobulin
      light chain was downregulated in MAK. Overall, a clear distinction in the
      transcriptional response to low temperature was seen in the two cell lines. To
      further elucidate the set of genes responsible for increased antibody
      productivity, the expression data of low temperature cultures was compared to
      that of butyrate treatment which increased specific antibody productivity in both
      cell lines. Genes which are commonly differentially expressed under conditions
      that increased productivity are likely to reflect functional classes that are
      important in the productivity changes. This comparative transcriptome analysis
      suggests that vesicle trafficking, endocytosis and cytoskeletal elements are
      involved in increased specific antibody productivity.

PMID- 18726961
TI  - Optimization of an enrichment process for circulating tumor cells from the blood
      of head and neck cancer patients through depletion of normal cells.
AB  - The optimization of a purely negative depletion, enrichment process for
      circulating tumor cells (CTCs) in the peripheral blood of head and neck cancer
      patients is presented. The enrichment process uses a red cell lysis step followed
      by immunomagnetic labeling, and subsequent depletion, of CD45 positive cells. A
      number of relevant variables are quantified, or attempted to be quantified, which
      control the performance of the enrichment process. Six different immunomagnetic
      labeling combinations were evaluated as well as the significant difference in
      performance with respect to the blood source: buffy coats purchased from the Red
      Cross, fresh, peripheral blood from normal donors, and fresh peripheral blood
      from human cancer patients. After optimization, the process is able to reduce the
      number of normal blood cells in a cancer patient's blood from 4.05 x 10(9) to
      8.04 x 10(3) cells/mL and still recover, on average, 2.32 CTC per mL of blood.
      For all of the cancer patient blood samples tested in which CTC were detected (20
      out of 26 patients) the average recovery of CTCs was 21.7 per mL of blood, with a
      range of 282 to 0.53 CTC. Since the initial number of CTC in a patient's blood is
      unknown, and most probably varies from patient to patient, the recovery of the
      CTC is unknown. However, spiking studies of a cancer cell line into normal blood,
      and subsequent enrichment using the optimized protocol indicated an average
      recovery of approximately 83%. Unlike a majority of other published studies, this
      study focused on quantifying as many factors as possible to facilitate both the
      optimization of the process as well as provide information for current and future
      performance comparisons. The authors are not aware any other reported study which
      has achieved the performance reported here (a 5.66 log(10)) in a purely negative
      enrichment mode of operation. Such a mode of operation of an enrichment process
      provides significant flexibility in that it has no bias with respect to what
      attributes define a CTC; thereby allowing the researcher or clinician to use any
      maker they choose to define whether the final, enrich product contains CTCs or
      other cell type relevant to the specific question (i.e., does the CTC have
      predominantly epithelial or mesenchymal characteristics?).

PMID- 18726963
TI  - In situ magnetic separation for extracellular protein production.
AB  - A new approach for in situ product removal from bioreactors is presented in which
      high-gradient magnetic separation is used. This separation process was used for
      the adsorptive removal of proteases secreted by Bacillus licheniformis. Small,
      non-porous bacitracin linked magnetic adsorbents were employed directly in the
      broth during the fermentation, followed by in situ magnetic separation. Proof of
      the concept was first demonstrated in shake flask culture, then scaled up and
      applied during a fed batch cultivation in a 3.7 L bioreactor. It could be
      demonstrated that growth of B. licheniformis was not influenced by the in situ
      product removal step. Protease production also remained the same after the
      separation step. Furthermore, degradation of the protease, which followed first
      order kinetics, was reduced by using the method. Using a theoretical modeling
      approach, we could show that protease yield in total was enhanced by using in
      situ magnetic separation. The process described here is a promising technique to
      improve overall yield in bio production processes which are often limited due to
      weak downstream operations. Potential limitations encountered during a bioprocess
      can be overcome such as product inhibition or degradation. We also discuss the
      key points where research is needed to implement in situ magnetic separation in
      industrial production.

PMID- 18726964
TI  - Cell-free synthesis of functional proteins using transcription/translation
      machinery entrapped in silica sol-gel matrix.
AB  - Herewith we report the encapsulation of functional protein synthesis machinery in
      a silica sol-gel matrix. When the sol-gel reaction using alkoxysilane monomers
      was carried out in the presence of Escherichia coli cell extract, macromolecular
      protein synthesis machinery in the cell extract was successfully immobilized
      within a silica gel matrix, catalyzing the translation of co-immobilized DNA when
      supplied with small-molecular-weight substrates for protein synthesis. The
      efficiency of protein synthesis was affected by the pore size of the gel
      structure, which was controlled through the use of appropriate additives during
      the sol-gel reactions. To the best of our knowledge, this is the first report
      describing the reproduction of the entire set of complicated biological process
      within an inorganic gel matrix, and we expect that the developed technology will
      find many applications in numerous fields such as high-throughput gene expression
      and the development of multifunctional biosensors.

PMID- 18726965
TI  - Towards in silico liquid crystals. Realistic transition temperatures and physical
      properties for n-cyanobiphenyls via molecular dynamics simulations.
AB  - We study the important n-cyanobiphenyl (with n= 4-8) series of mesogens, using
      modelling and molecular dynamics simulations. We are able to obtain spontaneously
      ordered nematics upon cooling isotropic samples of 250 molecules. By using the
      united-atom force field developed herein, we show that the experimental isotropic
      nematic transition temperatures are reproduced within 4 K, allowing a molecular
      level interpretation of the odd-even effect along the series. Other properties,
      like densities, orientational order parameters and NMR residual dipolar couplings
      are also reproduced well, demonstrating the feasibility of predictive in silico
      modelling of nematics from the molecular structure.

PMID- 18726966
TI  - Kinetics of helix-handedness inversion: folding and unfolding in aromatic amide
      oligomers.
AB  - A series of helically folded oligoamides of 8-amino-2-quinoline carboxylic acid
      possessing 6, 7, 8, 9, 10 or 16 units are prepared following convergent synthetic
      schemes. The right-handed (P) and the left-handed (M) helical conformers of these
      oligomers undergo an exchange slow enough to allow their chromatographic
      separation on a chiral stationary phase. Thus, the M conformer is isolated for
      each of these oligomers and its slow racemization in hexane/CHCl(3) solutions is
      monitored at various temperatures using chiral HPLC. The kinetics of racemization
      at different temperatures in hexane/CHCl(3) (75:25 vol/vol) are fitted to a first
      order kinetic model to yield the kinetic constant and the Gibbs energy of
      activation for oligomers having 6, 7, 8, 9, 10 or 16 quinoline units. This energy
      gives the first quantitative measure of the exceptional stability of the helical
      conformers of an aromatic amide foldamer with respect to its partly unfolded
      conformations that occur between an M helix and a P helix. The trend of the Gibbs
      energy as a function of oligomer length suggests that helix-handedness inversion
      does not require a complete unfolding of a helical strand and may instead occur
      through the propagation of a local unfolding separating two segments of opposite
      handedness.

PMID- 18726967
TI  - Reappraisal of endosonography of ampullary tumors: correlation with
      transabdominal sonography, CT, and MRI.
AB  - PURPOSE: To reappraise the accuracy of transabdominal sonography (US), CT, MRI,
      and endosonography (EUS) in the diagnosis and staging of ampullary tumors.
      METHOD: We reviewed the medical records and the images of 41 consecutive patients
      with ampullary tumors. Tumor detection rate and accuracy of TNM (tumor-node
      metastasis) staging of malignant tumors were determined. Imaging findings were
      correlated with histopathologic findings. RESULTS: The detection rates for
      ampullary tumors were 97.6% for EUS, 81.3% for MRI, 28.6% for CT, and 12.2% for
      US (p < 0.001 for EUS versus CT; p < 0.001 for EUS versus US; p > 0.05 for EUS
      versus MRI). The accuracy in T staging for ampullary carcinomas was 72.7% for
      EUS, 53.8% for MRI, and 26.1% for CT (p < 0.01 for EUS versus CT; p > 0.05 for
      EUS versus MRI). The accuracy in N staging for ampullary carcinomas was 66.7% for
      EUS, 76.9% for MRI, and 43.5% for CT with no statistically significant difference
      between the 3 modalities. The sensitivity in detecting malignant lymph nodes was
      46.7% for EUS, 25.0% for MRI, and 0% for CT (p < 0.01 for EUS versus CT; p > 0.05
      for EUS versus MRI; p > 0.05 for MRI versus CT). Transpapillary stenting,
      advanced tumor extension (>T2), large tumor size (>2 cm), tumor differentiation,
      and endoscopic appearance of tumor growth did not significantly influence EUS
      accuracy in T or N staging (p > 0.05). CONCLUSION: EUS was superior to CT and was
      equivalent to MRI for tumor detection and T and N staging of ampullary tumors.
      Neither indwelling stents nor tumor size, differentiation, or endoscopic
      appearance affected the staging accuracy of EUS.

PMID- 18726968
TI  - Sonographic assessment of uterine and ovarian development in normal girls aged 1
      to 12 years.
AB  - PURPOSE: To provide normal references of sonographic uterine and ovarian size in
      girls aged 1-12 years. METHOD: Ninety-nine girls were enrolled in the study (mean
      age +/- SD, 6.9 +/- 2.4 years [range, 1-12 years]). Pubertal status was
      classified according to Tanner staging, whereas for height and weight assessment
      a standard stadiometer and weight scale were employed. All subjects underwent
      pelvic sonographic examination for the measurement of uterine length, volume,
      ratio of anteroposterior diameter at the fundus divided by the anteroposterior
      diameter at the cervix (fundal-cervical [F/C] ratio), and ovarian volume and
      morphology. RESULTS: A gradual increase with age was observed in all uterine and
      ovarian measurements. Cubic model analysis provided the best curve estimation for
      uterine length, uterine volume, and ovarian volume in relation to age. Uterine
      length, uterine volume, ovarian volume and F/C ratio were significantly
      correlated to both age and height. With respect to ovarian morphology, there was
      a gradual decrease in frequency of the homogeneous and the paucicystic
      appearances with increasing age. The macrocystic appearance was observed after
      the age of 6 years, and its frequency increased gradually with age. CONCLUSION:
      There is a continuous increase in size of internal female genitalia from early
      childhood until the onset of puberty. We have provided reference percentile
      charts of normal uterine length, uterine volume, and ovarian volume in girls aged
      1-12 years.

PMID- 18726969
TI  - First-trimester prenatal sonographic diagnosis of omphalocele-exstrophy
      imperforate anus-spinal defects complex.
AB  - We describe a case of omphalocele-exstrophy-imperforate anus-spinal defects
      (OEIS) diagnosed at 13 weeks' gestation by ultrasound detection of a large
      multilocular ventral wall mass into which inserted the umbilical cord, and
      thoracic hemivertebrae with kyphoscoliosis. Subsequent sonographic examinations
      at 16 and 19 weeks revealed evolution of the ventral wall mass into a classic
      omphalocele. Clinicians should recognize the significance of a large multicystic
      ventral wall mass, which should lead to a search for other anomalies suggestive
      of OEIS complex.

PMID- 18726970
TI  - A novel covalent coupling method for coating of capillaries with liposomes in
      capillary electrophoresis.
AB  - A novel covalent coupling method for coating of capillaries with liposomes has
      been developed, which includes three steps: (i) epoxy-diol coating, (ii)
      activation with 2,2,2-trifluoroethanesulfonyl chloride, and (iii) liposome
      coupling. The coating conditions, such as the reaction time and temperature of
      liposome coupling, the content of dimyristoylphosphatidylethanolamine in
      liposomes, were optimized. Vesicles were visualized on the inner silica wall as
      confirmed by atomic force microscopy. The effectiveness of the coating was
      demonstrated by investigating the effect of pH of BGE on EOF and separating
      neutral compounds. The intra- and inter-capillary variations in EOF are 4.02% RSD
      (n=30) and 6.72% RSD (n=4) respectively, and the coated capillaries can be used
      to perform analysis at least for one month without any performance deterioration
      when stored at 4 degrees C. A set of drugs with diverse structures was applied
      into the developed liposome-coated CE. The normalized capacity factor (K) was
      introduced to quantitatively evaluate drug-membrane interactions. The
      relationship between log K and the fraction dose absorbed in humans (Fa%) shows
      that the liposome-coated CE can be utilized for in vitro prediction of Fa% of
      drugs that follow the transcellular passive transport route.

PMID- 18726971
TI  - Enzymatic assay of marine bacterial phosphatases by capillary electrophoresis
      with laser-induced fluorescence detection.
AB  - Microbial ectoenzyme activities in aquatic environments are important
      determinants of polymer hydrolysis and indicators of the state of microbial
      carbon, nitrogen, and phosphorus nutrition. Marine ectoenzymes are found on the
      cell surface or in the periplasmic space of gram-negative heterotrophic bacteria.
      Phosphatases, which remove phosphate groups from substrates, are one example of
      an ectoenzyme. Enzyme assays based on-capillary electrophoresis (CE) take
      advantage of CE's high-efficiency separation, extremely low sample volume
      requirements, and its ability to electrophoretically mix and separate zones of
      enzymes, substrates, and products all in one experimental run. CE has better
      resolving power and, when utilized with laser-induced fluorescence (LIF)
      detection, it is more sensitive than chromatography. CE-LIF is a promising tool
      for determining different phosphatases within a single microbial strain as well
      as the functional diversity between strains. In this study, four bacterial
      strains were studied (Shewanella sp., TW7, BB2AT2, and Vibrio alginolyticus) with
      each yielding at least one phosphatase that was kinetically characterized. K(m)
      values were calculated and found to be in the range of 0.0725-3.35 microM,
      whereas V(max) values ranged from 1.02 x 10(-3) to 1.05 x 10(-2) microM/min. The
      large range of values demonstrates differences among the phosphatases, suggesting
      different roles for each phosphatase not only between the species but also within
      a single bacterial species. This can have the important implications for organic
      matter processing in the sea.

PMID- 18726974
TI  - Turin: a European experience--take two.

PMID- 18726972
TI  - Apigenin suppresses insulin-like growth factor I receptor signaling in human
      prostate cancer: an in vitro and in vivo study.
AB  - Deregulation of insulin-like growth factor (IGF)-I/IGF-IR signaling has been
      implicated in the development and progression of prostate cancer. Agents that can
      suppress the mitogenic activity of the IGF/IGF-IR growth axis may be of
      preventive or therapeutic value. We have previously demonstrated that apigenin, a
      plant flavone, modulates IGF signaling through upregulation of IGFBP-3. In this
      study, we investigated the mechanism(s) of apigenin action on the IGF/IGF-IR
      signaling pathway. Exposure of human prostate cancer DU145 cells to apigenin
      markedly reduced IGF-I-stimulated cell proliferation and induced apoptosis.
      Apigenin inhibited IGF-I-induced activation of IGF-IR and Akt in DU145 cells.
      Similar growth inhibitory and apoptotic responses were observed in PC-3 cells,
      which constitutively overexpress this pathway. This effect of apigenin appears to
      be due partially to reduced autophosphorylation of IGF-IR. Inhibition of p-Akt by
      apigenin resulted in decreased phosphorylation of GSK-3beta along with decreased
      expression of cyclin D1 and increased expression of p27/kip1. In vivo
      administration of apigenin to PC-3 tumor xenografts inhibited tumor growth,
      resulted in IGF-IR inactivation and dephosphorylation of Akt and its downstream
      signaling. These results suggest that inhibition of cell proliferation and
      induction of apoptosis by apigenin are mediated, at least in part, by its ability
      to inhibit IGF/IGF-IR signaling and the PI3K/Akt pathway.

PMID- 18726976
TI  - Metal-free catalytic hydrogenation of enamines, imines, and conjugated
      phosphinoalkenylboranes.

PMID- 18726977
TI  - Synergistic binding of both Lewis acids and bases to phosphinidenes.

PMID- 18726978
TI  - Synthesis of optically active boron-silicon bifunctional cyclopropane derivatives
      through enantioselective copper(I)-catalyzed reaction of allylic carbonates with
      a diboron derivative.

PMID- 18726979
TI  - Multifunctional uniform nanoparticles composed of a magnetite nanocrystal core
      and a mesoporous silica shell for magnetic resonance and fluorescence imaging and
      for drug delivery.

PMID- 18726981
TI  - Intermolecular hydroarylation of unactivated olefins catalyzed by homogeneous
      platinum complexes.

PMID- 18726980
TI  - Merging porphyrins with organometallics: synthesis and applications.
AB  - The coordination chemistry of porphyrins has traditionally involved the ability
      of the porphyrin's tetrapyrrolic core to accommodate metal ions of varying
      charges and sizes, and on the organometallic chemistry of the resulting
      metalloporphyrins. However, the organometallic chemistry of porphyrins is not
      necessarily restricted to the metal bound in the porphyrin core, but can also be
      extended to the porphyrin periphery, be it through direct metalation of the
      porphyrin macrocycle at the meso or beta position, or by attachment to or merger
      of the porphyrin skeleton with ligands, followed by metalation. This Review
      focuses on the synthetic strategies used for porphyrins with peripheral metal
      carbon bonds. The exciting results that have been produced underscore the
      importance and future potential of this field.

PMID- 18726982
TI  - Association of genetic polymorphisms at 8q24 with the risk of prostate cancer in
      a Japanese population.
AB  - BACKGROUND: Genetic factors, as well as a combination of environmental factors,
      contribute to the risk of prostate cancer (PC). Recently, genome-wide linkage
      studies found several independent single nucleotide polymorphisms (SNPs) that are
      strongly associated with PC on chromosome 8q24. METHODS: We analyzed two of these
      SNPs, rs1447295 and rs6983267, to examine association with the risk of PC in
      Japanese men. These SNPs were examined by a mismatch PCR-RFLP method in 507 PC
      patients (286 aggressive and 221 non-aggressive) and in 511 non-PC patients (124
      benign prostatic hyperplasia and 387 normal male controls) and the allele
      frequencies were then compared between groups. RESULTS: The rs1447295 A allele
      was associated with susceptibility to PC (PC vs. non-PC: P = 0.041; OR, 1.28;
      95%CI = 1.01-1.61), and was more significantly associated with disease in
      aggressive PC (aggressive PC vs. normal controls, P = 0.013; OR, 1.43; 95%CI =
      1.08-1.90). The rs6983267 G allele did not show significant association with
      susceptibility to PC (PC vs. non-PC: P = 0.967; OR, 1.00; 95%CI = 0.83-1.21).
      However, it was associated with disease in non-aggressive PC (non-aggressive PC
      vs. normal controls: P = 0.0068; OR, 1.43; 95%CI = 1.10-1.85). CONCLUSIONS: The
      two SNPs at 8q24 were associated with an increased risk of prostate cancer and
      contributed to tumor aggression in Japanese men.

PMID- 18726983
TI  - Induction of FLIP expression by androgens protects prostate cancer cells from
      TRAIL-mediated apoptosis.
AB  - BACKGROUND: Prostate tumors initially regress in response to androgen-ablation
      therapy. However, most cancers eventually relapse with an androgen-depletion
      independent (ADI) phenotype that is often more aggressive than the original
      androgen-dependent (AD) tumor. Importantly, most relapsed tumors still rely upon
      androgen receptor (AR) activity for proliferation and survival. The cellular
      Fas/FasL-associated death domain protein-like inhibitory protein (FLIP) inhibits
      activation of procaspase-8 by death receptor-mediated signaling at the cell
      surface. In the current study, we examined the androgenic regulation of FLIP and
      its contribution to protecting prostate cancer cells from death receptor-mediated
      apoptosis. METHODS: FLIP expression in tissues from intact and castrated rats as
      well as androgen-treated prostate cancer cell lines (LNCaP, C4-2, LNCaP-Rf, and
      DU-145) was monitored via Real-Time RT-PCR and immunoblot. Induction of apoptosis
      by TRAIL, the death receptor ligand, was determined via microscopic observation
      and cell counting of fragmented nuclei following fixation and staining with
      Hoechst 33285. RESULTS: FLIP mRNA and protein expression was reduced following
      castration in multiple rat tissues, including dorsolateral prostate and seminal
      vesicles. Androgenic induction of FLIP mRNA and protein was observed in isogenic
      AD LNCaP and ADI LNCaP-Rf cells, but not the isogenic ADI C4-2 cell line.
      Protection from TRAIL-induced apoptosis by androgen was completely blocked when
      LNCaP-Rf cells were depleted of endogenous FLIP via siRNA transfection.
      CONCLUSIONS: Androgenic protection from TRAIL-induced apoptosis is predominantly
      via enhanced transcription of FLIP in prostate cancer cells. Loss of androgen
      sensitivity in ADI prostate cancer cells highlights this pathway as a potential
      target for future therapy of prostate cancer.

PMID- 18726984
TI  - Imaging the effects of castration on bone turnover and hormone-independent
      prostate cancer colonization of bone.
AB  - INTRODUCTION: Tumor populations may selectively colonize bone that is being
      actively remodeled. In prostate cancer patients, androgen deprivation directly
      inhibits tumor growth initially, whilst induced bone loss may facilitate tumor
      colonization of bone by androgen-insensitive cells. We have tested this
      hypothesis using a xenograft model of early growth of prostate cancer in bone.
      METHODS: PC3 cells transfected with Green fluorescent protein (GFP) were injected
      into castrated and non-castrated athymic mice via intrabial and intracardiac
      routes. In vivo tumor growth was monitored daily and animals sacrificed 6-9 days
      following initial GFP-based detection of tumors. Tumor bearing and contra-lateral
      non-tumor bearing tibias were analyzed extensively by micro-CT and
      histology/immunohistochemistry for the presence of tumor cells and the effects of
      tumor and/or castration on bone cells and bone structure evaluated. RESULTS: GFP
      positive tumors in bone were visible from 12 days post-injection following
      intratibial injection, allowing tumors <1 mm diameter to be monitored in live
      animals. Castration did not affect tumor frequency, tumor volume, or time to
      initial appearance of tumors injected via intratibial or intracardiac routes.
      Castration decreased trabecular bone volume in all mice. Significant tumor
      induced suppression of numbers of osteoblasts, coupled with increased numbers of
      activated osteoclasts, was evident in both intact animals and castrated animals.
      CONCLUSIONS: In vivo GFP imaging allows the detection of early tumor growth at
      intra-osseous sites. Castration induces bone loss, but PC3-GFP cells are also
      capable of inducing bone remodeling in intact animals at early time points,
      independently of pre-existing castration-induced alterations to bone.

PMID- 18726986
TI  - Differential association between MAOA, ADHD and neuropsychological functioning in
      boys and girls.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is more common in boys than in
      girls. It has been hypothesized that this sex difference might be related to
      genes on the X-chromosome, like Monoamine Oxidase A (MAOA). Almost all studies on
      the role of MAOA in ADHD have focused predominantly on boys, making it unknown
      whether MAOA also has an effect on ADHD in girls, and few studies have
      investigated the relationship between MAOA and neuropsychological functioning,
      yet this may provide insight into the pathways leading from genotype to
      phenotype. The current study set out to examine the relationship between MAOA,
      ADHD, and neuropsychological functioning in both boys (265 boys with ADHD and 89
      male non-affected siblings) and girls (85 girls with ADHD and 106 female non
      affected siblings). A haplotype was used based on three single nucleotide
      polymorphisms (SNPs) (rs12843268, rs3027400, and rs1137070). Two haplotypes (GGC
      and ATT) captured 97% of the genetic variance in the investigated MAOA SNPs. The
      ATT haplotype was more common in non-affected siblings (P = 0.025), conferring a
      protective effect for ADHD in both boys and girls. The target and direction of
      the MAOA effect on neuropsychological functioning was different in boys and
      girls: The ATT haplotype was associated with poorer motor control in boys (P =
      0.002), but with better visuo-spatial working memory in girls (P = 0.01). These
      findings suggest that the genetic and neuropsychological mechanisms underlying
      ADHD may be different in boys and girls and underline the importance of taking
      into account sex effects when studying ADHD.

PMID- 18726985
TI  - The dietary bioflavonoid, quercetin, selectively induces apoptosis of prostate
      cancer cells by down-regulating the expression of heat shock protein 90.
AB  - BACKGROUND: Human and animal studies have suggested that diet-derived flavonoids,
      in particular quercetin may play a beneficial role by preventing or inhibiting
      oncogenesis, but the underlying mechanism remains unclear. The aim of this study
      is to evaluate the effect(s) of quercetin on normal and malignant prostate cells
      and to identify the target(s) of quercetin's action. METHODOLOGY: We addressed
      this question using cells in culture and investigated whether quercetin affects
      key biological processes responsible for tumor cell properties such as cell
      proliferation and apoptosis and also studied the effect of quercetin on the
      proteome of prostate cancer cells using difference gel electrophoresis (DIGE) to
      assess changes in the expression of relevant proteins. RESULTS: Our findings
      demonstrate that quercetin treatment of prostate cancer cells results in
      decreased cell proliferation and viability. Furthermore, we demonstrate that
      quercetin promotes cancer cell apoptosis by down-regulating the levels of heat
      shock protein (Hsp) 90. Depletion of Hsp90 by quercetin results in decreased cell
      viability, levels of surrogate markers of Hsp90 inhibition (intracellular and
      secreted), induced apoptosis and activation of caspases in cancer cells but not
      in normal prostate epithelial cells. Knockdown of Hsp90 by short interfering RNA
      also resulted in induction apoptosis similar to quercetin in cancer cells as
      indicated by annexin V staining. CONCLUSION: Our results demonstrate that
      quercetin down-regulates the expression of Hsp90 which, in turn, induces
      inhibition of growth and cell death in prostate cancer cells while exerting no
      quantifiable effect on normal prostate epithelial cells.

PMID- 18726987
TI  - Teen workers' exposures to occupational hazards and use of personal protective
      equipment.
AB  - BACKGROUND: Prior research indicates that working adolescents seek care for the
      toxic effects of on-the-job chemical and environmental hazard exposures. METHODS:
      This cross-sectional survey of a nationally representative sample of 866
      adolescent workers in the retail and service sector examines their exposures,
      personal protective equipment (PPE) use, and training. RESULTS: Two-thirds of
      respondents were exposed to continuous, very loud noise, 55% to thermal hazards
      and 54% to chemical hazards. Few teens reported using any PPE, though those who
      had been trained reported somewhat higher usage. CONCLUSIONS: Teens working in
      the retail and service sectors experience a variety of chemical, thermal,
      biologic and noise exposures. Efforts to eradicate such exposures need to be
      complemented by increased provision of PPE and appropriate training in their use
      by employers.

PMID- 18726988
TI  - The impact of hearing conservation programs on incidence of noise-induced hearing
      loss in Canadian workers.
AB  - BACKGROUND: Noise exposure remains one of the most ubiquitous of occupational
      hazards. Hearing conservation program legislation and the programs themselves
      were designed to lower risk of resulting occupational noise-induced hearing loss,
      but there has been no broad-based effort to assess the effectiveness of this
      policy. METHODS: The incidence of a 10-dB standard threshold shift was examined
      in a group of Canadian lumber mill workers, using annual audiogram series
      obtained from the Workers' Compensation Board of British Columbia for the period
      1979-1996 and using Cox proportional hazard models. RESULTS: Mean cumulative
      noise exposure was 98.1 dB-years. The audiograms from 22,376 individuals, among
      whom there were 2,839 threshold shifts of 10 dB or greater (i.e., a "standard
      threshold shift"), were retained in multivariable analyses. After adjusting for
      potential confounders, continuous use of hearing protection, and initial hearing
      tests later in the study period, the risk for standard threshold shift was
      reduced by 30%. Risk increased sixfold, however, in those with the highest noise
      exposure. CONCLUSIONS: Hearing conservation programs may be effective in reducing
      overall incidence of hearing loss. In the absence of noise control at source,
      however, highly exposed workers remain at unnecessary risk.

PMID- 18726989
TI  - Cross-modal transfer of the conditioned eyeblink response during interstimulus
      interval discrimination training in young rats.
AB  - Eyeblink classical conditioning (EBC) was observed across a broad developmental
      period with tasks utilizing two interstimulus intervals (ISIs). In ISI
      discrimination, two distinct conditioned stimuli (CSs; light and tone) are
      reinforced with a periocular shock unconditioned stimulus (US) at two different
      CS-US intervals. Temporal uncertainty is identical in design with the exception
      that the same CS is presented at both intervals. Developmental changes in
      conditioning have been reported in each task beyond ages when single-ISI learning
      is well developed. The present study sought to replicate and extend these
      previous findings by testing each task at four separate ages. Consistent with
      previous findings, younger rats (postnatal day--PD23 and 30) trained in ISI
      discrimination showed evidence of enhanced cross-modal influence of the short CS
      US pairing upon long CS conditioning relative to older subjects. ISI
      discrimination training at PD43-47 yielded outcomes similar to those in adults
      (PD65-71). Cross-modal transfer effects in this task therefore appear to diminish
      between PD30 and PD43-47. Comparisons of ISI discrimination with temporal
      uncertainty indicated that cross-modal transfer in ISI discrimination at the
      youngest ages did not represent complete generalization across CSs. ISI
      discrimination undergoes a more protracted developmental emergence than single
      cue EBC and may be a more sensitive indicator of developmental disorders
      involving cerebellar dysfunction.

PMID- 18726990
TI  - "APRIL hath put a spring of youth in everything": Relevance of APRIL for
      survival.
AB  - A proliferation inducing ligand (APRIL or TALL-2 and TRDL-1) was first discovered
      as a cytokine over-expressed in many transformed cells and with the capacity to
      stimulate proliferation. APRIL was shown to bind two different receptors of the
      TNF receptor superfamily: B cell maturation antigen (BCMA) and transmembrane
      activator and calcium modulator and cyclophilin ligand interactor (TACI), as well
      as heparan sulphate proteoglycans (HSPGs). APRIL has since been shown to play a
      physiological role in B cell biology, in particular the survival of plasma B
      cells in a specialized APRIL-rich niche. However, aberrant expression of APRIL
      and the subsequent activation of pro-survival pathways, is potentially the
      driving force for the survival of several B cell malignancies. APRIL has
      therefore become an important therapeutic target, but many questions regarding
      its mechanism of action still remain. It is for instance unclear what the exact
      physiological implications of the APRIL-HSPG interaction could be. Neither do we
      know the precise signals elicited by APRIL in normal or in malignant cells, and
      whether blocking these effects could provide real therapeutic gain in cancer
      patients. In this review we discuss the specific relevance of APRIL for cell
      survival, in terms of both its physiological role and its role in tumor biology,
      and highlight some of the key questions that will undoubtedly form the basis of
      future research in this field.

PMID- 18726991
TI  - Calpain-mediated androgen receptor breakdown in apoptotic prostate cancer cells.
AB  - Since androgen receptor (AR) plays an important role in prostate cancer
      development and progression, androgen-ablation has been the frontline therapy for
      treatment of advanced prostate cancer even though it is rarely curative. A
      curative strategy should involve functional and structural elimination of AR from
      prostate cancer cells. We have previously reported that apoptosis induced by
      medicinal proteasome-inhibitory compound celastrol is associated with a decrease
      in AR protein levels. However celastrol-stimulated events contributing to this AR
      decrease have not been elucidated. Here, we report that a variety of
      chemotherapeutic agents, including proteasome inhibitors, a topoisomerase
      inhibitor, DNA-damaging agents and docetaxel that cause cell death, decrease AR
      levels in LNCaP prostate cancer cells. This decrease in AR protein levels was not
      due to the suppression of AR mRNA expression in these cells. We observed that a
      proteolytic activity residing in cytosol of prostate cancer cells is responsible
      for AR breakdown and that this proteolytic activity was stimulated upon induction
      of apoptosis. Interestingly, proteasome inhibitor celastrol- and chemotherapeutic
      drug VP-16-stimulated AR breakdown was attenuated by calpain inhibitors
      calpastatin and N-acetyl-L-leucyl-L-leucyl-L-methioninal. Furthermore, AR
      proteolytic activity pulled down by calmodulin-agarose beads from celastrol
      treated PC-3 cells showed immunoreactivity to a calpain antibody. Taken together,
      these results demonstrate calpain involvement in proteasome inhibitor-induced AR
      breakdown, and suggest that AR degradation is intrinsic to the induction of
      apoptosis in prostate cancer cells.

PMID- 18726992
TI  - Reproductive and hormonal risk factors for postmenopausal luminal, HER-2
      overexpressing, and triple-negative breast cancer.
AB  - BACKGROUND: Molecular profiling studies have identified subtypes of breast cancer
      that can be approximately classified by estrogen receptor (ER), progesterone
      receptor (PR), and HER-2/neu (HER-2) expression. These molecular subtypes are
      prognostically significant, but to the authors' knowledge, differences in their
      etiologic profiles have not been established. Reproductive factors may plausibly
      be differentially correlated with the risk of different breast cancer subtypes
      because these factors are presumed to impact exposure to endogenous sex hormones.
      METHODS: The authors pooled 2 population-based, case-control studies of breast
      cancer in women ages 55 to 79 years for an analysis including 1476 controls and
      1023 cases of luminal breast cancer, 39 cases of HER-2-overexpressing breast
      cancer, and 78 cases of triple-negative breast cancer. Polytomous logistic
      regression was used to compare each case group with controls. RESULTS:
      Associations varied by molecular subtype. Early age at menarche was only found to
      be associated with risk of HER-2-overexpressing disease (odds ratio [OR] of 2.7;
      95% confidence interval [95% CI], 1.4-5.5), whereas breastfeeding for > or =6
      months was only found to be protective for luminal and triple-negative disease
      (OR of 0.8 [95% CI, 0.6-1.0] and OR of 0.5 [95% CI, 0.3-0.9], respectively). Both
      late age at menopause and the use of estrogen plus progestin hormone therapy were
      only found to be associated with risk of luminal disease (OR of 1.6 [95% CI, 1.1
      2.2] and OR of 1.7 [95% CI, 1.3-2.1], respectively). No differences in risks
      associated with parity or age at first live birth were observed by subtype.
      CONCLUSIONS: Certain reproductive factors may have a greater impact on the risk
      of certain molecular subtypes of disease compared with others. Future studies
      that further define the etiology of breast cancer subtypes will add to the
      biologic understanding of this disease.

PMID- 18726993
TI  - Incense use and respiratory tract carcinomas: a prospective cohort study.
AB  - BACKGROUND: Incense use is an integral part of daily life in large parts of Asia.
      The burning of incense is a powerful producer of particulate matter and the smoke
      contains a multitude of well-characterized carcinogens. However, to the authors'
      knowledge, no convincing association has been reported between exposure to
      incense smoke and the development of cancer. Therefore, the relation between
      incense use and the risk of respiratory tract carcinomas was analyzed in a
      prospective cohort study. METHODS: Between 1993 and 1998, a population-based
      cohort of 61,320 Singapore Chinese who were free of cancer and ages 45 to 74
      years completed a comprehensive interview regarding living conditions and dietary
      and lifestyle factors. Through linkage to population-based registries, the cohort
      was followed through 2005 and cancer occurrence determined. The relative risk for
      these cancers associated with incense use was estimated using a Cox proportional
      hazards model. RESULTS: A total of 325 upper respiratory tract (UPT) carcinomas
      and 821 lung carcinomas were observed during follow-up. Incense use was
      associated with a significantly increased risk of UPT carcinomas other than
      nasopharyngeal, whereas no overall effect was observed on lung cancer. The
      duration and intensity of incense use were associated with an increased risk of
      squamous cell carcinomas in the entire respiratory tract (P for trend = .004),
      whereas there was no significant association noted between incense use and
      nonsquamous cell carcinomas. The relative risk of squamous cell carcinomas among
      long-term incense users was 1.8 (95% confidence interval [95% CI], 1.2-2.6; P =
      .004) in the entire respiratory tract. CONCLUSIONS: The results of the current
      study indicate that long-term use of incense is associated with an increased risk
      of squamous cell carcinoma of the respiratory tract.

PMID- 18726994
TI  - Optimal dose and schedule of an HER-2/neu (E75) peptide vaccine to prevent breast
      cancer recurrence: from US Military Cancer Institute Clinical Trials Group Study
      I-01 and I-02.
AB  - BACKGROUND: E75, a HER-2/neu-derived peptide, was administered as a preventive
      vaccine with granulocyte-macrophage-colony-stimulating factor (GM-CSF) in disease
      free lymph node-positive (NP) and lymph node-negative (NN) breast cancer (BCa)
      patients. The optimal biologic dose (OBD) was determined based on toxicity and
      immunologic response. METHODS: Patients were vaccinated over 6 months (3, 4, or 6
      times) with different doses of E75 plus GM-CSF. Toxicities were graded per
      National Cancer Institute Common Terminology Criteria. GM-CSF was reduced for
      significant toxicity. Immunologic response was measured by delayed type
      hypersensitivity test (DTH), and E75-specific CD8+ T-cells were quantified with
      human leukocyte antigen-A2:immunoglobulin G dimer and flow cytometry. RESULTS:
      Ninety-nine patients (48 NP and 51 NN) were vaccinated in 7 dose groups. The OBD
      was 1000 microg E75 plus 250 microg GM-CSF monthly x 6. The optimal dose group
      (ODG, n = 29) experienced similar toxicities to the suboptimal dose group (SDG, n
      = 70), which was comprised of the remaining 6 groups. The ODG demonstrated a
      trend toward an increase in the average postvaccine dimer (0.87 +/- 0.10% vs 0.67
      +/- 0.05%; P = .07), a significantly larger DTH response (21.5 +/- 2.5 mm vs 11.3
      +/- 1.3 mm; P = .0002), and a trend toward decreased recurrences (3.4% vs 12.9%;
      P = .27). Compared with the SDG, the ODG had larger tumors (percentage > or =T2:
      55% vs 23%; P = .004), more positive lymph nodes (percentage NP: 76% vs 37%; P =
      .001), and higher grade tumors (percentage grade 3: 52% vs 30%; P = .07), but a
      shorter median follow-up time (20 months vs 32 months; P < .001). CONCLUSIONS:
      Compared with suboptimally dosed patients, the optimally dosed E75 vaccine in
      disease-free BCa patients had similar toxicity but enhanced HER-2/neu-specific
      immunity that may lead to decreased recurrences with additional follow-up.

PMID- 18726996
TI  - The use of mesenchymal (skeletal) stem cells for treatment of degenerative
      diseases: current status and future perspectives.
AB  - Human bone marrow derived-mesenchymal (skeletal) stem (MSC) cells are a group of
      non-hematopoietic stem cells residing in the perivascular niches in bone marrow.
      These cells have the capacity to differentiate mainly into mesoderm-type cells
      such as osteoblasts, chondrocytes and adipocytes and possibly but not proven to
      non-mesodermal cell types. Recently, there has been an increased interest in
      understanding the biology of MSC due to their potential use in cell-based therapy
      for multiple degenerative diseases. Here, we will provide an update on the
      current status of these novel therapeutic opportunities. J. Cell. Physiol. 218: 9
      12, 2009. (c) 2008 Wiley-Liss, Inc.

PMID- 18726995
TI  - Thrombospondin-1-induced apoptosis of brain microvascular endothelial cells can
      be mediated by TNF-R1.
AB  - Thrombospondin-1 (TSP-1) treatment of dermal microvascular endothelial cells
      (MvEC) has been shown to upregulate Fas ligand (FasL) and to induce apoptosis by
      a mechanism that requires caspase-8 activity. We have examined the potential anti
      angiogenic effects of TSP-1 on primary human brain MvEC. The addition of TSP-1 to
      primary human brain MvEC cultured as monolayers on type 1 collagen, induced cell
      death and apoptosis (evidenced by caspase-3 cleavage) in a dose- (5-30 nM) and
      time-dependent (maximal at 17 h) manner. TSP-1 treatment for 17 h induced caspase
      3 cleavage that required caspase-8 activity and the tumor necrosis factor
      receptor 1 (TNF-R1). We did not find a requirement for Fas, or the tumor necrosis
      related apoptosis-inducing ligand receptors (TRAIL-R) 1 and 2. We confirmed the
      findings using caspase inhibitors, blocking antibodies and small interfering RNA
      (siRNA). Further analysis indicated that the TSP-1 induction of caspase-3
      cleavage of primary human brain MvEC adherent to collagen required the synthesis
      of new message and protein, and that TSP-1 induced the expression of TNFalpha
      mRNA and protein. Consistent with these findings, when the primary human brain
      MvEC were propagated on collagen gels mAb anti-TNF-R1 reversed the inhibitory
      effect, in part, of TSP-1 on tube formation and branching. These data identify a
      novel mechanism whereby TSP-1 can inhibit angiogenesis-through induction of
      apoptosis in a process mediated by TNF-R1.

PMID- 18726997
TI  - Composition and significance of detergent resistant membranes in mouse
      spermatozoa.
AB  - Mammalian spermatozoa acquire the ability to fertilize an oocyte as they ascend
      the female reproductive tract. This process is characterized by a complex cascade
      of biophysical and biochemical changes collectively know as "capacitation." The
      attainment of a capacitated state is accompanied by a dramatic reorganization of
      the surface architecture to render spermatozoa competent to recognize the oocyte
      and initiate fertilization. Emerging evidence indicates that this process is
      facilitated by molecular chaperone-mediated assembly of a multimeric receptor
      complex on the sperm surface. However, the mechanisms responsible for gathering
      key recognition molecules within this putative complex have yet to be defined. In
      this study, we provide the first evidence that chaperones partition into
      detergent resistant membrane fractions (DRMs) within capacitated mouse
      spermatozoa and co-localize in membrane microdomains enriched with the lipid raft
      marker, G(M1) ganglioside. During capacitation, these microdomains coalesce
      within the apical region of the sperm head, a location compatible with a role in
      sperm-zona pellucida interaction. Significantly, DRMs isolated from spermatozoa
      possessed the ability to selectively bind to the zona pellucida of unfertilized,
      but not fertilized, mouse oocytes. A comprehensive proteomic analysis of the DRM
      fractions identified a total of 100 proteins, a number of which have previously
      been implicated in sperm-oocyte interaction. Collectively, these data provide
      compelling evidence that mouse spermatozoa possess membrane microdomains that
      provide a platform for the assembly of key recognition molecules on the sperm
      surface and thus present an important mechanistic insight into the fundamental
      cell biological process of sperm-oocyte interaction.

PMID- 18726999
TI  - Ferritin and FasL (CD95L) mediate density dependent apoptosis in primary rat
      hepatocytes.
AB  - Based on a recent description of an apoptosis stimulating property for hepatocyte
      derived isoferritins, this investigation demonstrates that ferritin, released in
      vitro from hepatocytes substantially contributes to density dependent apoptosis
      in primary hepatocytes and is significantly (P < or = 0.05) inhibited by anti-H
      ferritin antibody rH02. Furthermore, total protein release and albumin secretion
      rapidly decline in a time and density dependent mode under serum-free conditions,
      whereas ferritin secretion, which is upregulated at initial stages of primary
      culture is not affected by cell density. Supplementation with dexamethasone (DEX)
      or proliferative stimulation by epidermal growth factor (EGF) and insulin
      strongly suppresses density dependent apoptosis. Both regimens have previously
      been shown to inhibit isoferritin mediated apoptosis in hepatocytes, most likely
      by interrupting proapotitc mitochondrial signalling. Finally, FasL/Fas also
      participates in density dependent apoptosis, since apoptosis is significantly (P
      < or = 0.005) reduced in high density cultures supplemented with an anti-FasL
      antibody. This antibody has also been shown to neutralise ferritin mediated
      apoptosis in primary hepatocytes, suggesting a linkage of ferritin and Fas in
      density dependent apoptosis. In conclusion, ferritin contributes to apoptosis in
      primary hepatocytes in an autocrine, density dependent mode, involving Fas
      stimulation and proapoptotic mitochondrial signalling. With respect to liver
      physiology, these findings may indicate that ferritin plays a yet unrecognised
      role as an acute phase signalling molecule in early stages of tissue repair and
      liver regeneration, and may also be responsible for the limited ability to
      propagate human hepatocytes in culture and the limited expansion of donor cells
      in the recipient liver upon cell transplantation.

PMID- 18726998
TI  - The effect of differentiation on 1,25 dihydroxyvitamin D-mediated gene expression
      in the enterocyte-like cell line, Caco-2.
AB  - We examined 1,25 dihydroxyvitamin D (1,25(OH)(2)D(3))-induced expression of 25
      hydroxyvitamin D(3) 24-hydroxylase (CYP24) and apical calcium channel (TRPV6)
      mRNA levels in 2-, 9-, and 15-day cultures Caco-2 cells that model proliferating,
      post-proliferative, and differentiated enterocytes. 1,25(OH)(2)D(3)-induced (10
      nM, 8 h) CYP24 and TRPV6 mRNA levels were significantly greater in differentiated
      and post-proliferative than proliferating Caco-2 cells (>16X and >3X,
      respectively). Neither CYP24 mRNA half-life nor induction of a -298 bp rat CYP24
      promoter-luciferase reporter construct (10 nM 1,25(OH)(2)D(3), 24 h) were
      different between proliferating and post-proliferating Caco-2 cells. We next
      tested whether the blunted response of natural genes to 1,25(OH)(2)D(3) in
      proliferating Caco-2 cells is due to altered chromatin remodeling. VDR and
      coactivator protein levels do not increase with differentiation but the level of
      the co-repressor Alien falls by 50% with differentiation. Over-expression of
      Alien reduced 1,25(OH)(2)D(3)-induced activity of a minimal VDRE containing
      promoter-luciferase construct by more than 60% in differentiated Caco-2 cells
      while siRNA knockdown of Alien in proliferating Caco-2 cells increased
      1,25(OH)(2)D(3)-induced CYP24 mRNA level by 40%. These observations suggest that
      Alien is a regulator of VDR-mediated gene transcription in Caco-2 cells. In
      addition, we found that 1,25(OH)(2)D(3)-induced association of VDR with chromatin
      and with the CYP24 promoter was lower in proliferating cells. This suggests that
      decreased recruitment of VDR to vitamin D response elements also contributes to
      the blunted transcriptional responsiveness to 1,25(OH)(2)D(3) in proliferating
      Caco-2 cells.

PMID- 18727000
TI  - Simultaneous Doppler tracing of the mitral inflow and annular motion provides a
      useful means of evaluating left ventricular diastolic function.
AB  - BACKGROUND: In this study, we evaluated the feasibility and clinical usefulness
      of TS(E-E(') ), the time interval between the onsets of early diastolic mitral
      inflow velocity (E) and mitral annular velocity (E'), obtained by simultaneously
      tracing E and E', in terms of evaluating diastolic function. METHODS: By the
      diastolic functional status, 105 patients were allocated to abnormal relaxation,
      pseudonormal filling (PN), or normal diastolic function groups (n = 30, 43, and
      32, respectively). The TS(E-E(') ) was measured in the same cardiac cycle by the
      pulsed-wave Doppler (PWD) tracing of mitral inflow near the septal annulus with
      appropriate filter and gain settings. RESULTS: TS(E-E(') ) was prolonged in the
      PN group versus the normal group (34.1 +/- 12.2 msec versus 12.1 +/- 8.5 msec, p<
      or =0.001). The area under the receiver operating characteristic curve of TS(E
      E(') ) for the detection of PN was 0.91 (95% confidence interval [CI]; 0.85
      approximately 0.97, p<0.001), and 24.0 msec was determined to be the optimal cut
      off value (specificity 83.7%, sensitivity 90.3%). CONCLUSION: Simultaneous
      measurement of TS(E-E(') ) is feasible and clinically applicable for the grading
      of diastolic dysfunction (DD).

PMID- 18727001
TI  - Atrioventricular block: a serious complication in and after transcatheter closure
      of perimembranous ventricular septal defects.
AB  - BACKGROUND: Transcatheter closure is an effective approach for perimembranous
      ventricular septal defects (PMVSD). However, atrioventricular blocks (AVB)
      emerged possibly due to the close proximity of the PMVSD to the conduction
      system, but concern for the complication was not adequately emphasized. In this
      study, we report the incidence of AVBs, in and after transcatheter closure of a
      PMVSD, and the outcome of the complication in our center. METHODS: One hundred
      and sixty-eight PMVSD patients were accepted for transcatheter closure with
      Amplazter PMVSD occluder (AGA Medical, Plymouth, Minn., USA). The procedure was
      discontinued when a second- or third-degree AVB occurred. A steroid was
      administered to all patients who developed AVBs. Temporary pacemakers were
      inserted in patients who developed a complete AVB or Mobitz type II AVB during or
      after the procedure. RESULTS: During the follow-up period of 6-24 mo (mean 10.6
      +/- 3.9), the incidence of AVBs occurring during or after transcatheter closure
      of PMVSD was 3.5%. The AVB disappeared quickly after discontinuing the procedure
      in patients who developed AVBs during the procedure, whereas the AVBs disappeared
      between 2 and 21 d (mean 8.0 +/- 8.8) in the patients who developed AVBs after
      the procedure. However, complete right bundle branch block (CRBBB) was observed,
      and a transient complete AVB emerged after 8 mo in 1 case, incomplete right
      bundle branch block (IRBBB) in 1 case, and CRBBB and left anterior hemiblock
      (LAH) in 1 case. CONCLUSIONS: The AVB is a serious complication during and after
      transcathter closure of PMVSD. More attention should be paid to the complication,
      and multicentres are required to monitor the complication.

PMID- 18727002
TI  - Anti-Inflammatory effects of low-level laser therapy (660 nm) in the early phase
      in carrageenan-induced pleurisy in rat.
AB  - BACKGROUND AND OBJECTIVE: In the classic model of pleurisy there is little
      evidence about the anti-inflammatory effects of low-level laser therapy (LLLT) as
      well the dosage characteristics, such as wavelength, total energy, number and
      pattern of treatment. In this study we investigated the potential effects of LLLT
      on modulating the pro-inflammatory and anti-inflammatory mediators of acute
      inflammation in a rat pleurisy model. STUDY DESIGN/MATERIALS AND METHODS: A
      sample of 48 female Wistar rats were divided into control and experiential
      groups. An inflammation was induced by carrageenan (0.2 ml) injected into the
      pleural cavity. At 1, 2, and 3 hours after induction a continuous wave (20 mW)
      diode laser of the InGaAlP (660 nm) type was used in the four laser groups with
      different doses and treatment patterns. One group received a single dose of 2.1 J
      and the other three groups received a total energy of 0.9, 2.1, and 4.2 J. Four
      hours later the exudate volume, total and differential leukocytes, protein
      concentration, NO, IL-6, IL-10, TNF-alpha, and MCP-1 were measured from the
      aspirated liquid. RESULTS: All the treatment patterns and quantity of energy
      studied show significant reduction of the exudate volume (P<0.05). Using energy
      of 0.9 J only NO, IL-6, MCP-1 and IL-10 are significantly reduced (P<0.05). On
      the other hand, higher energies (2.1 and 4.2 J) significantly reduce all
      variables independently of the treatment pattern. The neutrophil migration has a
      straight correlation with the TNF-alpha (r = 0.551) and NO (r = 0.549)
      concentration. CONCLUSIONS: LLLT-660 nm induced an anti-inflammatory effect
      characterized by inhibition of either total or differential leukocyte influx,
      exudation, total protein, NO, IL-6, MCP-1, IL-10, and TNF-alpha, in a dose
      dependent manner. Under these conditions, laser treatment with 2.1 J was more
      effective than 0.9 and 4.2 J.

PMID- 18727003
TI  - Alcohol, wine, and cardiovascular health.
AB  - Studies evaluating the health benefits of alcohol and wine have demonstrated that
      moderate consumption is associated with a decrease in all-cause and
      cardiovascular mortality. Various populations and alcoholic beverages exhibit
      this effect to different degrees. Alcoholic beverages exhibit multiple mechanisms
      that may favorably influence cardiac risk potential actions on platelets,
      antioxidants, fibrinolysis, and lipids. However, other data suggest that the
      perceived benefit of alcoholic beverages in general, and wine in particular, are
      the result of socioeconomic confounders. In the absence of more rigorous
      evidence, it is not currently possible to define the role of wine in human
      health.

PMID- 18727004
TI  - The continuing value of invasive coronary angiography.
AB  - In 1975, Gofredo Gensini stated, "The primary goal of coronary arteriography is
      the identification, localization, and assessment of obstructive lesions present
      within the arteries of the heart." The operative word here is assessment. I
      interpret assessment to mean determining the pathophysiologic significance
      (ischemia versus no ischemia) of the coronary stenosis in question.

PMID- 18727006
TI  - Analysis of major proteins and fat fractions associated with mare's milk fat
      globules.
AB  - Although several studies have aimed to identify mare's milk proteins, only the
      major whey proteins and some caseins have yet been characterized. Incomplete
      sequencing of the equine genome and the difficulty of recovering highly
      hydrophobic proteins mean that little is known to date about the proteins
      associated with milk fat globules, which have been shown to play an important
      role in newborns' defense mechanisms. The fat fraction, in particular the
      distribution of unsaturated fatty acids, has been more extensively studied, but
      complex lipids are only partially elucidated. This study reports a 2-DE approach
      combined with a powerful method for de novo protein sequencing, and quali
      quantitative data on complex lipid composition determined by high performance TLC
      (HPTLC) and GC. The presence in mare's milk of long-chain highly unsaturated
      fatty acids, and the evidence of close similarity between equine and human milk
      fat globule membrane proteins, support the use of mare's milk for human
      nutrition.

PMID- 18727007
TI  - Knockouts of Se-glutathione peroxidase-1 and Cu,Zn superoxide dismutase exert
      different impacts on femoral mechanical performance of growing mice.
AB  - The objective of this study was to determine the impact of knockout of Cu,Zn
      superoxide dismutase (SOD1) and Se-glutathione peroxidase-1 (GPX1) on murine bone
      biomechanical properties. Femora samples were collected from wild-type (WT), SOD1
      knockout [SOD1(-/-)] and GPX1-knockout [GPX1(-/-)] female mice (9-wk old, n = 7-8
      per genotype) to assay for bone enzyme activities and mechanical properties in
      three point bending. Prior to testing, all mice were fed a torula yeast diet
      supplemented with 0.4 mg Se/kg as sodium selenite. Compared with the WT mice,
      SOD1(-/-) mice displayed a series of reductions (p < 0.05): 24% in body mass, 8%
      in femoral length, 43% in femoral structural strength, and 32% in bending
      stiffness. When differences in body size were accounted for, femoral failure
      moment in SOD1(-/-) mice remained lower (p < 0.05) than that of WT. Femoral
      tartrate resistant acid phosphatase activity in SOD1(-/-) was 47% greater (p <
      0.05) than the WT. In contrast, GPX1(-/-) mice showed no significant differences
      in femoral mechanical properties from those of WT mice. In conclusion, knockout
      of SOD1 exerted a greater impact on femoral mechanical characteristics than that
      of GPX1 in growing mice.

PMID- 18727008
TI  - Mechanisms of selenium chemoprevention and therapy in prostate cancer.
AB  - Prostate cancer (PC) chemoprevention has generated considerable interest in the
      last decade and selenium and combinations of selenium have been recognized as one
      of the most efficacious chemopreventive agents against PC. This review focuses on
      a discussion of the knowledge hitherto gained about the mechanisms of action of
      the various in vitro and in vivo used selenium compounds and their effects on
      cellular processes and signaling pathways. We also describe the clinical and
      preclinical studies that have contributed enormously to the knowledge about dose,
      duration of exposure, and the chemical form of selenium effective in different
      scenarios. Even though the jury is still out about whether selenium can be used
      as a chemopreventive agent in the clinic and whether studies with cell lines and
      populations at low, medium, or high risk can adequately represent the
      physiological behavior of this micronutrient, it can safely be said to offer the
      most diverse spectrum of protective effects against this particular type of
      cancer which may augur well for its future as a chemopreventive agent.

PMID- 18727009
TI  - Alternariol acts as a topoisomerase poison, preferentially affecting the IIalpha
      isoform.
AB  - Alternariol (AOH), a mycotoxin formed by Alternaria alternata, has been reported
      to possess genotoxic properties. However, the underlying mechanism of action is
      unclear. Here, we tested the hypothesis that interactions with DNA-topoisomerases
      play a role in the DNA-damaging properties of AOH. First we compared DNA-damaging
      properties of AOH with other Alternaria mycotoxins such as AOH monomethyl ether
      (AME), altenuene and isoaltenuene. AOH and AME significantly increased the rate
      of DNA strand breaks in human carcinoma cells (HT29, A431) at micromolar
      concentrations, whereas altenuene and isoaltenuene did not affect DNA integrity
      up to 100 microM. Next, we selected AOH as the most DNA-damaging Alternaria
      metabolite for further studies of interactions with DNA topoisomerases. In cell
      free assays, AOH potently inhibited DNA relaxation and stimulated DNA cleavage
      activities of topoisomerase I, IIalpha and IIbeta. Stabilisation of covalent
      topoisomerase II-DNA intermediates by AOH was also detectable in cell culture,
      and here, the IIalpha isoform was preferentially targeted. AOH is thus
      characterised as a poison of topoisomerase I and II with a certain selectivity
      for the IIalpha isoform. Since topoisomerase poisoning and DNA strand breakage
      occurred within the same concentration range, poisoning of topoisomerase I and II
      might at least contribute to the genotoxic properties of AOH.

PMID- 18727010
TI  - High level expression, purification and physico- and immunochemical
      characterisation of recombinant Pen a 1: a major allergen of shrimp.
AB  - Well-characterised and immunologically active recombinant allergens are of
      eminent importance for improvement of diagnostic tools and immunotherapy of
      allergic diseases. The use of recombinant allergens has several advantages such
      as the more precise quantification of the active substance compared to allergen
      extracts and the reduced risk of contamination with other allergenic proteins
      compared to purified natural allergens. Optimised standard protocols for
      expression and purification and a detailed physico-chemical characterisation of
      such recombinant allergens are necessary to ensure consistent quality and
      comparability of results obtained with recombinant material. In this study the
      major allergen Pen a 1 of brown shrimp (Penaeus aztecus) was expressed in E. coli
      and purified in two steps by immobilised metal chelate-affinity chromatography
      (IMAC) and size-exclusion chromatography. Identity and purity were verified with
      N-terminal sequencing and peptide mass fingerprinting. Circular dichroism and NMR
      spectroscopy indicated an alpha-helical flexible structure of rPen a 1 which is
      in accordance with the known structure of tropomyosins. Finally, the recombinant
      allergen proved to be immunologically reactive in IgE Western blot analysis and
      ELISA. This study provides a protocol for the preparation of recombinant shrimp
      tropomyosin in standardised quality.

PMID- 18727011
TI  - Relationship between the physicochemical properties of starches and the glycemic
      indices of some Jamaican yams (Dioscorea spp.).
AB  - Starch granules from round leaf yellow yam (RY), Lucea yam (LY), white yam (WY),
      and Chinese yam (CY) grown in Jamaica were isolated and the relationship between
      starch amylose content, crystallinity, microscopic properties, in vitro
      digestibility, and the glycemic index (GI) of the tubers was investigated. The
      results indicate that RY had the highest amylose content (265.30 +/- 0.09 g/kg
      starch) while CY the lowest (111.44 +/- 0.03 g/kg starch). A corresponding
      variation in starch digestibility and GI was also observed, as CY which had the
      highest in vitro digestibility had the highest GI (21.27 +/- 0.01 and 97.42 +/-
      0.62%, respectively), while RY, LY, and WY starches with low digestibility had
      lowest GI. Differences in the crystalline pattern of the different starches were
      observed, where RY, LY, and WY displayed the type B crystalline pattern while CY
      had the intermediate crystallite (type C).

PMID- 18727012
TI  - Does the lipid membrane composition of arsonoliposomes affect their anticancer
      activity? A cell culture study.
AB  - Sonicated arsonoliposomes were prepared using arsonolipid with palmitic acid acyl
      chain (C16), mixed with phosphatidylcholine (PC)-based or 1,2-distearoyl-sn
      glycero-3-phosphocholine (DSPC)-based, and cholesterol (Chol) with C16/DSPC/Chol
      8:12:10 molar ratio. PEG-lipid (1,2-distearoyl-sn-glycero-3-phosphoethanolamine
      conjugated to polyethylenoglycol 2000) containing vesicles (PEGylated
      arsonoliposomes; PC-based and DSPC-based) were also prepared. The cytotoxicity of
      these arsonoliposomes towards different cancer cells (human promyelocytic
      leukaemia NB4, Prostatic cancer PC3, human breast adenocarcinoma MDA-MB-468,
      human T-lymphocyte (MT-4) and also towards human umbilical vein endothelial cells
      (HUVECs) was evaluated by calculating the arsonoliposome-induced growth
      inhibition of the cells by the MTT assay. IC-50 values were interpolated from
      cell number/arsonoliposome concentration curves. The results reveal that all
      types of arsonoliposomes evaluated significantly inhibit the growth of most of
      the cancer cells studied (PC3, NB4, MT4) with the exception of the MDA-MB-468
      breast cancer cells which were minimally affected by arsonoliposomes; in some
      cases even less than HUVEC. Nevertheless, for the same cell type the differences
      between the different types of arsonoliposomes were significant but not
      proportional to their stability, indicating that the formation of arsonoliposomes
      with very stable membranes is not a problem for their anticancer activity.
      Thereby it is concluded that arsonoliposome composition should be adjusted in
      accordance to their in vivo kinetics and the desired, for each specific
      application, biodistribution of As and/or encapsulated drug.

PMID- 18727013
TI  - Transepithelial transport across Caco-2 cell monolayers of antihypertensive egg
      derived peptides. PepT1-mediated flux of Tyr-Pro-Ile.
AB  - This paper examines the in vitro transepithelial transport of antihypertensive
      peptides derived from egg proteins using Caco-2 cell monolayers. Ovokinin
      (FRADHPFL) was absorbed intact through the Caco-2 cell epithelium, although it
      was also susceptible to the action of brush-border aminopeptidases that yielded
      shorter fragments prior to their transport. The tripeptide YPI was resistant to
      cellular peptidases and transported through the monolayer, what suggests that the
      reduction in systemic blood pressure caused by this peptide may be mediated by
      effects at tissue level. Its pathway for transepithelial absorption was examined
      using inhibitors of the different mechanisms for oligopeptide transport in the
      intestinal tract. The main route involved in the transepithelial flux of YPI is
      probably the peptide H(+)-coupled transporter PepT1. These results highlight the
      potential of antihypertensive peptides to be used in the formulation of
      functional foods.

PMID- 18727014
TI  - Purification and characterisation of a panel of peanut allergens suitable for use
      in allergy diagnosis.
AB  - Peanut is a major cause of type 1 hypersensitive reactions including anaphylaxis.
      This results from the presence of a number of protein allergens, six of which are
      being studied as part of the EU FP6 EuroPrevall programme. These are Ara h 1 (7S
      globulin), Ara h 2, Ara h 6 (2S albumins), Ara h 3/4 (11S globulins) and Ara h 8
      (Bet v 1 homologue). Methods for the purification of Ara h 1, Ara h 3/4, Ara h 2
      and Ara h 6 from peanut seeds and for the production of recombinant Ara h 8 in
      Escherichia coli are described with spectroscopic analyses being used to confirm
      that they are authentically folded. N-terminal sequencing of the proteins
      purified from peanut seeds also revealed details of the differences between
      isoforms and their generation by proteolytic processing within the seed.
      Preliminary IgE binding studies of the purified allergens confirmed that they
      retained their immunological properties indicating their suitability for use in
      allergy diagnosis.

PMID- 18727015
TI  - Anthocyanins and their metabolites are weak inhibitors of cytochrome P450 3A4.
AB  - The cytochrome P450 enzyme cytochrome P450 3A4 (CYP3A4) controls the metabolism
      of about 60% of all drugs, and its inhibition may dramatically affect drug
      safety. Modulation of cytochrome P450 activity has been observed by constituents
      of fruit extracts including several flavonoids. The present investigation
      addresses CYP3A4 inhibition by anthocyanins, their aglycons, proanthocyanidins,
      and phenolic metabolites using a chemiluminescent assay. Test compounds inhibited
      CYP3A4 activity in a concentration-dependent manner featuring IC(50) values from
      12.2 up to 7,842 microM. In the order of decreasing effect size, anthocyanidins
      were followed by anthocyanins, proanthocyanidins, and phenolic acids. When
      compared to earlier data on furanocoumarins from grapefruit extract, the
      inhibitory activity of tested anthocyanins, and anthocyanidins was shown to be
      about 10,000-fold weaker, and was negligible for phenolic acids (>100 000-fold
      weaker). Future studies are invited to address effects of the above flavonoids on
      other CYP isoforms for more detailed toxicity profiles.

PMID- 18727018
TI  - Fermentative butanol production by Clostridia.
AB  - Butanol is an aliphatic saturated alcohol having the molecular formula of
      C(4)H(9)OH. Butanol can be used as an intermediate in chemical synthesis and as a
      solvent for a wide variety of chemical and textile industry applications.
      Moreover, butanol has been considered as a potential fuel or fuel additive.
      Biological production of butanol (with acetone and ethanol) was one of the
      largest industrial fermentation processes early in the 20th century. However,
      fermentative production of butanol had lost its competitiveness by 1960s due to
      increasing substrate costs and the advent of more efficient petrochemical
      processes. Recently, increasing demand for the use of renewable resources as
      feedstock for the production of chemicals combined with advances in biotechnology
      through omics, systems biology, metabolic engineering and innovative process
      developments is generating a renewed interest in fermentative butanol production.
      This article reviews biotechnological production of butanol by clostridia and
      some relevant fermentation and downstream processes. The strategies for strain
      improvement by metabolic engineering and further requirements to make
      fermentative butanol production a successful industrial process are also
      discussed.

PMID- 18727019
TI  - Low density, non-ablative fractional CO2 laser rejuvenation.
AB  - BACKGROUND AND OBJECTIVES: Fractional skin rejuvenation has gained increased
      interest since its introduction in 2003. Both non-ablative and ablative lasers as
      well as different treatment techniques have been devised. Recent clinical studies
      indicate that a paradigm of low spot density combined with high fluences tend to
      produce better clinical results and less risk of post-inflammatory
      hyperpigmentation in darker skin types. The present study is focused on
      investigations of the clinical outcome by non-ablative fractional CO(2)
      treatments with a single pass with low spot density. METHODS AND MATERIALS: A
      CO(2) laser was equipped with a scanner enabling it to perform fractional
      treatments with 36, 64 or 100 microthermal zones (MTZ)/cm(2). Twelve patients
      participated in the study. The perioral area was treated three times with 1-month
      intervals using a spot density of 64 MTZ/cm(2), a spot diameter of 0.5 mm, a
      micro-beam energy of 36-60 mJ, and a pulse duration of 3-5 milliseconds. Follow
      up was performed 3 months after the last treatment. RESULTS: At the 3-month
      follow-up 72.7% of the volunteers had obtained improvement in
      ultrasonographically determined dermal density, and the average improvement was
      40.2% (SD: 48.0%). This improvement was statistically significant (P<0.006).
      Eighty percent of the volunteers rated the reduction in visible perioral wrinkles
      to be fair, good or excellent. For reduction of irregular pigmentation, fair,
      good or excellent clearance was reported by 62.5% of the volunteers. CONCLUSIONS:
      The present study demonstrates subjective improvements in wrinkles, skin texture
      and mottled pigmentation as well as statistically significant objectively
      measured improvements in ultrasonographical dermal density after three non
      ablative fractional CO(2) laser treatments.

PMID- 18727020
TI  - In vivo nonmelanoma skin cancer diagnosis using Raman microspectroscopy.
AB  - BACKGROUND AND OBJECTIVES: Nonmelanoma skin cancers, including basal cell
      carcinoma (BCC) and squamous cell carcinoma (SCC), are the most common skin
      cancers, presenting nearly as many cases as all other cancers combined. The
      current gold-standard for clinical diagnosis of these lesions is histopathologic
      examination, an invasive, time-consuming procedure. There is thus considerable
      interest in developing a real-time, automated, noninvasive tool for nonmelanoma
      skin cancer diagnosis. In this study, we explored the capability of Raman
      microspectroscopy to provide differential diagnosis of BCC, SCC, inflamed scar
      tissue, and normal tissue in vivo. STUDY DESIGN: Based on the results of previous
      in vitro studies, we developed a portable confocal Raman system with a handheld
      probe for clinical study. Using this portable system, we measured Raman spectra
      of 21 suspected nonmelanoma skin cancers in 19 patients with matched normal skin
      spectra. These spectra were input into nonlinear diagnostic algorithms to predict
      pathological designation. RESULTS: All of the BCC (9/9), SCC (4/4), and inflamed
      scar tissues (8/8) were correctly predicted by the diagnostic algorithm, and 19
      out of 21 normal tissues were correctly classified. This translates into a 100%
      (21/21) sensitivity and 91% (19/21) specificity for abnormality, with a 95%
      (40/42) overall classification accuracy. CONCLUSIONS: These findings reveal Raman
      microspectroscopy to be a viable tool for real-time diagnosis and guidance of
      nonmelanoma skin cancer resection.

PMID- 18727021
TI  - Topical delivery of methotrexate via skin pretreated with physical enhancement
      techniques: low-fluence erbium:YAG laser and electroporation.
AB  - BACKGROUND AND OBJECTIVE: The high hydrophilicity and molecular weight of
      methotrexate (MTX) make it difficult to deliver via the skin route for treating
      psoriasis or rheumatoid arthritis. The objective of this study was to enhance and
      optimize the skin permeation of MTX using two physical techniques: an
      erbium:yttrium-aluminum-garnet (Er:YAG) laser and electroporation. METHODS: In
      vitro skin permeation was performed using horizontal side-by-side diffusion
      cells. The animal model utilized nude mice. The skin where epidermal
      hyperproliferation was reproduced by repeated barrier abrogation was also used as
      a permeation barrier for MTX delivery. RESULTS: Application of the laser and
      electroporation significantly enhanced the permeation of MTX. The enhancing
      effect was more pronounced after applying the laser. Er:YAG laser pretreatment on
      the skin produced a 3- to 80-fold enhancement dependent upon the magnitude of the
      laser fluence. Using electroporation, treatment with 10 pulses resulted in a
      twofold increase in MTX flux. A combination of laser pretreatment and subsequent
      electroporation for 10 minutes resulted in a higher drug permeation than either
      technique alone. However, this synergistic effect was only observed when the
      lower laser fluence (1.4 J/cm(2)) was applied. Hyperproliferative skin generally
      showed a greater variability of MTX flux and lower permeation. CONCLUSION: The
      results shown in the present study encourage further investigation of laser- and
      electroporation-assisted topical drug delivery.

PMID- 18727022
TI  - A possible mechanism for visible light-induced wound healing.
AB  - BACKGROUND AND OBJECTIVES: Chronic wounds resistant to conventional therapy have
      been treated successfully with low energy lasers and light emitting diodes (LEDs)
      in the visible and near IR region. It has been proposed that production of low
      level reactive oxygen species (ROS) following illumination is the first step of
      photobiomodulation. It was also shown that white light (400-800 nm) has similar
      stimulatory effects as lasers and LEDs. ROS at higher levels are toxic to cells
      and bacteria. STUDY DESIGN/MATERIALS AND METHODS: In the present study, we
      examined the phototoxicity of broadband (400-800 nm, 120 J/cm(2)) visible light
      on the survival of several pathogenic bacteria: Staphylococcus aureus 195,
      Pseudomonas aeruginosa 1316, Escherichia coli 1313, and Serratia marcescens.
      These bacteria were chosen due to their high prevalence in infected wounds. The
      survival of bacterial cells following illumination was monitored by counting the
      number of colony forming units before and after exposure to light. RESULTS:
      Illumination with white light, 120 J/cm(2), caused a reduction of 62%, 83%, and
      56% in the colony count of E. coli 1313, S. aureus 195 and S. marcescens,
      respectively, though no reduction in the viability of P. aeruginosa 1316 was
      demonstrated. The phototoxic effect was found to involve induction of ROS
      production by the bacteria. It was also found that illumination of S. aureus 195
      and E. coli 1313 in the presence of pyocyanin, known to be secreted by P.
      aeruginosa, had a stronger bactericidal effect compared to illumination alone.
      CONCLUSION: Visible light at high intensity can kill bacteria in infected wounds.
      Thus, illumination of infected wounds with intense visible light, prior to low
      intensity illumination for stimulating wound closure, may reduce infection and
      promote healing.

PMID- 18727024
TI  - Unipolar versus bipolar radiofrequency treatment of rhytides and laxity using a
      mobile painless delivery method.
AB  - BACKGROUND: Previous studies have shown that radiofrequency (RF) energy is a safe
      and effective treatment for rhytide-reduction. OBJECTIVE: This randomized,
      blinded, split-face study assesses the safety and efficacy of the unipolar versus
      bipolar handpieces on an RF device with a mobile delivery method for the
      treatment of rhytides and laxity using quantitative grading. METHODS: In this
      randomized, blinded, split-face design study, 10 subjects (aged 18-75 years) with
      a clinically observable excess of rhytides and laxity (minimum grade 2 out of 4)
      on the face received four treatments at 1-week intervals with random assignment
      of unipolar RF to one side and bipolar RF to the contralateral side. Each side
      received approximately four passes per treatment delivered in a mobile continuous
      manner. Results were evaluated by two blinded investigators of photographs
      employing a comprehensive 4-point grading scale at baseline, and 1- and 3-month
      follow-up visits after the final treatment. RESULTS: All subjects completed and
      responded to treatment. The blinded evaluations demonstrated the following mean
      percent improvements in grading scores of rhytides and laxity: for the unipolar
      side 6.0+/-4.6% and 4.6+/-4.8% versus the bipolar side 4.4+/-2.5 and 7.3+/-3.5%.
      The degree of improvement approached but did not achieve statistical significance
      for either handpiece, but demonstrated a trend toward improvement (P = 0.5599
      unipolar vs. 0.1108 bipolar). The treatment was painless (rated 0 out of 10 by
      all subjects) and side effects included minimal erythema which resolved within 1
      3 hours. No crusting, dyspigmentation or scarring was observed. CONCLUSION: This
      randomized, split-face study with blinded evaluations employing a quantitative
      grading scale demonstrated that minimal pass, mobile energy delivery serial
      treatments with either the unipolar or bipolar handpieces of a novel RF device
      appears to safe and painless. Each handpiece demonstrated minimal clinical
      efficacy which was not statistically significant, but with a trend toward
      improvement in rhytides and laxity of facial skin.

PMID- 18727025
TI  - Minimizing superficial thermal injury using bilateral cryogen spray cooling
      during laser reshaping of composite cartilage grafts.
AB  - Composite cartilage grafts were excised from New Zealand rabbit ears. Flat
      composite grafts (of cartilage and overlying skin graft on both surfaces) were
      obtained from each ear and cut into a rectangle measuring 50 mm by 25 mm (x by y)
      with an average thickness of approximately 1.3 mm (z), skin included. Specimens
      were manually deformed with a jig and maintained in this new position during
      laser illumination. The composite cartilage grafts were illuminated on the
      concave surface with an Nd:YAG laser (1,064 nm, 3 mm spot) at 10 W, 20 W, 30 W,
      40 W, 50 W. Cryogen spray cooling (CSC) was applied to both exterior (convex) and
      interior (concave) surfaces of the tissue to reduce thermal injury to the grafts.
      CSC was delivered: (1) in controlled applications (cryogen released when surface
      reached 40 degrees C, and (2) receiving only laser at above wattage, no CSC
      [representing the control group]. The specimens were maintained in a deformation
      for 15 minutes after illumination and serially examined for 14 days. The control
      group with no CSC caused injury to all specimens, ranging from minor to full
      thickness epidermal thermal injury. Although most levels of laser and CSC yielded
      a high degree of reshaping over an acute time period, after 14 days specimens
      exposed to 30 W, 40 W, 50 W retained shape better than those treated at 10 W and
      20 W. The specimens exposed to 50 W with controlled CSC retained its new shape to
      the highest degree over all others, and thermal injury was minimal. In
      conclusion, combinations of laser and CSC parameters were effective and practical
      for the reshaping of composite cartilage grafts.

PMID- 18727026
TI  - Effects of laser repetition rate on corneal tissue ablation for 193-nm excimer
      laser light.
AB  - BACKGROUND AND OBJECTIVE: The goal of the present work is to assess whether
      bovine corneal ablations generated at laser repetition rates of up to 400 Hz are
      comparable to ablations performed at rates consistent with current clinical laser
      systems. STUDY DESIGN/MATERIALS AND METHODS: A combination of experiments was
      used to assess a comprehensive range of ablation parameters, including ablation
      plume dynamics via imaging and transmission, corneal ablation profiles via
      scanning interferometry, and high-resolution electron microscopy of collagen
      structure following ablation. RESULTS: Using white-light interferometry analysis,
      no statistical difference was found between corneal ablation profiles created at
      60 and 400 Hz, with an average rate of 0.94 microm/pulse at 60 Hz versus 0.92
      microm/pulse at 400 Hz. In addition, based on plume imaging and transmission
      studies, the bulk ablation plume was found to dissipate on a time-scale less than
      the pulse-to-pulse separation for a laser repetition rate up to about 400 Hz. A
      persistent, diffuse gas-phase component of the ablation products was observed and
      concluded to be comparable at both repetition rates. Finally, SEM and TEM
      analysis revealed no signs of differential thermal tissue damage, including
      collagen fibril analysis, for laser repetition rates up to 400 Hz. CONCLUSIONS:
      In summary, investigation of the relative effects of excimer laser repetition
      rate on the overall corneal ablation metrics revealed no measurable difference
      under conditions typical of clinical refractive procedures. This study suggests
      that increases in ArF laser repetition rates for clinical applications (up to
      approximately 400 Hz) appear feasible.

PMID- 18727027
TI  - Scar prevention by laser-assisted scar healing (LASH): a pilot study using an 810
      nm diode-laser system.

PMID- 18727028
TI  - Measuring tissue heat penetration by scattered light measurements.
AB  - BACKGROUND AND OBJECTIVES: The monitoring of tissue morphological changes during
      clinical procedure such as laser thermotherapy, laser hair removal and others is
      important in order to prevent damage to healthy tissue. An optical system and
      method for the assessment of real time in vivo tissue morphological changes is
      proposed. MATERIALS AND METHODS: We used ex vivo chicken breast as tissue
      samples. The samples were irradiated by CO(2) laser to create thermal structural
      changes. The optical properties of the tissue samples were measured using an
      integrating sphere method. We measured the tissue heat penetration and the
      scattered light from the tissue and compared the results to Monte-Carlo
      simulation. RESULTS: Thermal interaction causes structural changes in the tissue.
      Therefore changing (increasing) the scattering properties of the tissue. We
      relate the structural changes to the scattered light pattern and proposed a
      method for controlling the thermal interaction. CONCLUSION: It is possible to
      design a real time in vivo controlling system for laser tissue thermal
      interaction that utilizes the changes in the scattered light pattern.

PMID- 18727029
TI  - Rapid cloning and purification of proteins: gateway vectors for protein
      purification by self-cleaving tags.
AB  - We have combined Invitrogen's Gateway cloning technology with self-cleaving
      purification tags to generate a new system for rapid production of recombinant
      protein products. To accomplish this, we engineered our previously reported
      DeltaI-CM cleaving intein to include a Gateway cloning recognition sequence, and
      demonstrated that the resulting Gateway-competent intein is unaffected. This
      intein can therefore be used in several previously reported purification methods,
      while at the same time being compatible with Gateway cloning. We have
      incorporated this intein into a set of Gateway vectors, which include self
      cleaving elastin-like polypeptide (ELP), chitin binding domain (CBD), phasin
      (polyhydroxybutyrate-binding), or maltose binding domain (MBD) tags. These
      vectors were verified by Gateway cloning of TEM-1 beta-lactamase and Escherichia
      coli catalase genes, and the expressed target proteins were purified using the
      four methods encoded on the vectors. The purification methods were unaffected by
      replacing the DeltaI-CM intein with the Gateway intein. It was observed that some
      purification methods were more appropriate for each target than others,
      suggesting utility of this technology for rapid process identification and
      optimization. The modular design of the Gateway system and intein purification
      method suggests that any tag and promoter can be trivially added to this system
      for the development of additional expression vectors. This technology could
      greatly facilitate process optimization, allowing several targets and methods to
      be tested in a high-throughput manner.

PMID- 18727030
TI  - Role of methoxypolyethylene glycol on the hydration, activity, conformation and
      dynamic properties of a lipase in a dry film.
AB  - A combined approach based on the use of ATR-FT/IR and steady-state fluorescence
      spectroscopy allowed to shed light on the effects of the additive
      methoxypolyethylene glycol (MePEG) on the hydration, conformation and dynamic
      properties of lipase from Burkholderia cepacia dehydrated to form a film.
      Spectroscopic data show that the additive has little effect on the structure of
      the protein; however, H/D exchange kinetic and fluorescence anisotropy suggest a
      more flexible enzyme molecule when in the presence of MePEG. By infrared
      spectroscopy, we estimated that, after conditioning the films at water activity
      of 1, the water content in the lipase dehydrated with MePEG is 5.4- and 4.7-fold
      higher than in the absence of the additive and the additive alone, respectively.
      Additionally, our infrared data suggest that MePEG acts by hindering
      intermolecular protein-protein interactions and contributing to increase the
      accessibility and flexibility of the lipase in the dehydrated solid film. These
      factors also explain the enhancement of the enzyme catalytic activity (i.e., up
      to 3.7-fold in neat organic solvent) when in the presence of MePEG. The method
      and results presented might better address the use of additives for the
      preparation of enzymes employed in non-aqueous media or of proteins used in a dry
      form in different fields of biotechnology.

PMID- 18727031
TI  - Mobilizing agents enhance fungal degradation of polycyclic aromatic hydrocarbons
      and affect diversity of indigenous bacteria in soil.
AB  - The impact of several mobilizing agents (MAs) (i.e., soybean oil, Tween-20, Tween
      80, olive-oil mill wastewaters, and randomly methylated beta-cyclodextrins) on
      the degradation performances of the white-rot fungi Irpex lacteus and Pleurotus
      ostreatus was comparatively assessed in a soil spiked with a mixture of seven
      polycyclic aromatic hydrocarbons (PAHs). Among the different MAs, soybean oil
      best supported the growth of both fungi that was twice that observed in soil in
      the absence of MAs. In addition, soybean oil positively affected PAH degradation
      by both fungi. In this case, the total weight of organic contaminants (TWOC) was
      lower than that in the absence of MAs (57.7 vs. 201.3 and 26.3 vs. 160.4 mg kg(
      1) with I. lacteus and P. ostreatus, respectively). On the other hand, the number
      of cultivable heterotrophic bacteria was significantly lower in the soil with
      soybean oil augmented with either one of the two fungi (5.21 vs. 8.71 and 0.22
      vs. 0.51 x 10(7) CFU g(-1) soil with I. lacteus and P. ostreatus, respectively).
      The effect of soybean oil was confirmed by denaturing gradient gel
      electrophoresis (DGGE) analysis of PCR-amplified 16S rRNA genes that showed a
      general decrease in biodiversity. The impact of the other MAs on bacterial
      diversity was either slightly negative or positive in incubation controls. Both
      richness and Shannon-Weaver index decreased upon treatment with P. ostreatus.
      Moreover, with this fungus the composition of the indigenous bacteria was not
      significantly affected by the type of MA used. By contrast, both indices
      increased in soil with I. lacteus in the presence of randomly methylated beta
      cyclodextrins (39 vs. 33 and 1.43 vs. 1.26, respectively) and soybean oil (19 vs.
      5 and 1.01 vs. 0.65, respectively).

PMID- 18727033
TI  - Effects of oxygen on mouse embryonic stem cell growth, phenotype retention, and
      cellular energetics.
AB  - Most embryonic stem (ES) cell research is performed with a gas phase oxygen
      partial pressure (pO(2)) of 142 mmHg, whereas embryonic cells in early
      development are exposed to pO(2) values of 0-30 mmHg. To understand effects of
      these differences, we studied murine ES (mES) growth, maintenance of stem cell
      phenotype, and cell energetics over a pO(2) range of 0-285 mmHg, in the presence
      or absence of differentiation-suppressing leukemia inhibitory factor (LIF). With
      LIF, growth rate was sensitive to pO(2) but constant with time, and expression of
      self-renewal transcription factors decreased at extremes of pO(2). Subtle
      morphological changes suggested some early differentiation, but cells retained
      the ability to differentiate into derivatives of all three germ layers at low
      pO(2). Without LIF, growth rate decreased with time, and self-renewal
      transcription factor mRNA decreased further. Gross morphological changes
      occurred, and overt differentiation occurred at all pO(2). These findings
      suggested that hypoxia in the presence of LIF promoted limited early
      differentiation. ES cells survived oxygen starvation with negligible cell death
      by increasing anaerobic metabolism within 48 h of anoxic exposure. Decreasing
      pO(2) to 36 mmHg or lower decreased oxygen consumption rate and increased lactate
      production rate. The fraction of ATP generated aerobically was 60% at or above
      142 mmHg and decreased to 0% under anoxia, but the total ATP production rate
      remained nearly constant at all pO(2). In conclusion, undifferentiated ES cells
      adapt their energy metabolism to proliferate at all pO(2) between 0 and 285 mmHg.
      Oxygen has minimal effects on undifferentiated cell growth and phenotype, but may
      exert more substantial effects under differentiating conditions.

PMID- 18727035
TI  - Human bone derived cell culture on PLGA flat sheet membranes of different
      lactide:glycolide ratio.
AB  - Providing a scaffold that can supply nutrients on a large scale (several cubic
      centimeters) is the key to successfully regenerating vascularized tissue:
      biodegradable membranes are a promising new scaffold suited to this purpose.
      Poly(lactic-co-glycolic-acid) (PLGA) flat sheet membranes of different
      lactide:glycolide ratios, prepared by phase inversion using 1-methyl-2
      pyrrolidinone (NMP) as the solvent and water as the nonsolvent, were compared by
      assessing attachment, proliferation and osteogenic function of human bone derived
      cells (HBDC). Three different lactide:glycolide ratios, 50:50, 75:25, and 100:0,
      were compared to tissue culture polystyrene (TCPS). For attachment, 50:50 and
      75:25 had similar numbers to TCPS but 100:0 had significantly fewer cells than
      TCPS. 50:50 and 75:25 had significantly lower HBDC numbers after 7 days but 100:0
      had similar numbers compared to TCPS. For proliferation the cell number on the
      membranes were similar to each other. After 3 weeks, osteoblastic function of the
      HBDC, shown by mineralization and alkaline phosphatase activity, was present but
      was significantly lower compared to the TCPS control but similar when the
      membranes were compared. PLGA membranes fabricated from a range of ratios support
      HBDC culture so the optimum scaffold composition can be selected based on other
      factors, such as degradation rate.

PMID- 18727036
TI  - Nutrient gradients in engineered cartilage: metabolic kinetics measurement and
      mass transfer modeling.
AB  - Since tissue-engineered cartilage is avascular, both nutrient supply and
      metabolic waste removal rely on diffusion. As a result, gradients of nutrients
      and wastes exist through the construct. Previous models usually calculate
      gradients of oxygen, glucose, and lactic acid separately, without taking into
      account the complex interdependence between concentrations of these substrates
      and rates of metabolism. In this study, these interactions were experimentally
      examined and incorporated into diffusion models. One-dimensional diffusion
      reaction models were developed for three typical culture conditions, that is,
      static culture, perfusion culture, and suspended culture. The profiles of oxygen,
      glucose, lactic acid, and pH in the cultured constructs were calculated
      simultaneously using measured metabolic rates. The maximum construct size and
      cell density which could be supported before nutrients were depleted in the
      construct center was identified; a function predicting the relationship between
      construct dimension and the maximum viable cell density was developed. For
      constructs incubated under static culture the model demonstrated that the
      gradients which developed through the medium could not be neglected. Perfusion
      cultures could support a considerably higher cell density than static cultures,
      while for batch cultures in a rotating bioreactor, the volume of medium also
      influences the maximum cell density that could be supported. This study provides
      useful guidance for design of engineered cartilage constructs.

PMID- 18727037
TI  - Voxel-shift and interpolation for hadamard-encoded MR images.
AB  - Although Fourier gradient phase-encoding and Hadamard radio-frequency encoding
      are two established spatial MR localization techniques, the absence of voxel
      shift and interpolation postprocessing algorithms for the latter has always
      placed it at a discouraging disadvantage. This article presents a method for
      voxel-shift and interpolation of Hadamard-encoded data and demonstrates both
      theoretically and experimentally the similarities of the respective operations
      between the two localization methods.

PMID- 18727038
TI  - Tracking the effects of crusher gradients on gradient-echo BOLD signal in space
      and time during rat sensory stimulation.
AB  - A unique method to map the effect of crusher gradients in space and time on the
      gradient echo blood oxygen level dependent (BOLD) signal is introduced. Using the
      Radial Correlation Contrast (RCC) analysis method, amplitude-RCC maps at
      different time segments and different gradient strengths were obtained. The ratio
      of amplitude-RCC cluster volumes, with and without crusher gradients, showed a
      temporal dependency with stronger volume reduction for stimulation-onset versus
      stimulation-decline. Aside from signal-to-noise ratio reduction in diffusion
      weighted images, the average temporal patterns were equal. Comparison of the data
      with and without crushers showed a stronger reduction in local coherence for
      stimulation-onset times. We hypothesize that the stimulation decline was weighted
      by extravascular effects originating in expanded veins due to their larger volume
      and long range susceptibility which couples neighboring voxels. The ratio of
      amplitude-RCC with and without crushers calculated for each voxel at each time
      segment yielded a spatial-temporal mapping of the crusher effect. These maps
      suggest that early stimulation-onset ( approximately 9 s) is weighted by flow;
      later a dynamic steady-state between intra- and extravascular effects is
      obtained. Stimulation-decline was dominated by extravascular effects, and at late
      stimulation decline as well as at early stimulation onset, clusters were small
      and localized to expected site of neuronal activity.

PMID- 18727039
TI  - Improved calibration technique for in vivo proton MRS thermometry for brain
      temperature measurement.
AB  - The most common MR-based approach to noninvasively measure brain temperature
      relies on the linear relationship between the (1)H MR resonance frequency of
      tissue water and the tissue's temperature. Herein we provide the most accurate in
      vivo assessment existing thus far of such a relationship. It was derived by
      acquiring in vivo MR spectra from a rat brain using a high field (11.74 Tesla
      [T]) MRI scanner and a single-voxel MR spectroscopy technique based on a LASER
      pulse sequence. Data were analyzed using three different methods to estimate the
      (1)H resonance frequencies of water and the metabolites NAA, Cho, and Cr, which
      are used as temperature-independent internal (frequency) references. Standard
      modeling of frequency-domain data as composed of resonances characterized by
      Lorentzian line shapes gave the tightest resonance-frequency versus temperature
      correlation. An analysis of the uncertainty in temperature estimation has shown
      that the major limiting factor is an error in estimating the metabolite
      frequency. For example, for a metabolite resonance linewidth of 8 Hz, signal
      sampling rate of 2 Hz and SNR of 5, an accuracy of approximately 0.5 degrees C
      can be achieved at a magnetic field of 3T. For comparison, in the current study
      conducted at 11.74T, the temperature estimation error was approximately 0.1
      degrees C.

PMID- 18727040
TI  - Reproducibility study of whole-brain 1H spectroscopic imaging with automated
      quantification.
AB  - A reproducibility study of proton MR spectroscopic imaging ((1)H-MRSI) of the
      human brain was conducted to evaluate the reliability of an automated 3D in vivo
      spectroscopic imaging acquisition and associated quantification algorithm. A
      PRESS-based pulse sequence was implemented using dualband spectral-spatial RF
      pulses designed to fully excite the singlet resonances of choline (Cho), creatine
      (Cre), and N-acetyl aspartate (NAA) while simultaneously suppressing water and
      lipids; 1% of the water signal was left to be used as a reference signal for
      robust data processing, and additional lipid suppression was obtained using
      adiabatic inversion recovery. Spiral k-space trajectories were used for fast
      spectral and spatial encoding yielding high-quality spectra from 1 cc voxels
      throughout the brain with a 13-min acquisition time. Data were acquired with an 8
      channel phased-array coil and optimal signal-to-noise ratio (SNR) for the
      combined signals was achieved using a weighting based on the residual water
      signal. Automated quantification of the spectrum of each voxel was performed
      using LCModel. The complete study consisted of eight healthy adult subjects to
      assess intersubject variations and two subjects scanned six times each to assess
      intrasubject variations. The results demonstrate that reproducible whole-brain
      (1)H-MRSI data can be robustly obtained with the proposed methods.

PMID- 18727041
TI  - MRI of the basement membrane using charged nanoparticles as contrast agents.
AB  - The integrity of the basement membrane is essential for tissue cellular growth
      and is often altered in disease. In this work a method for noninvasively
      detecting the structural integrity of the basement membrane, based on the
      delivery of cationic iron-oxide nanoparticles, was developed. Cationic particles
      accumulate due to the highly negative charge of proteoglycans in the basement
      membrane. The kidney was used to test this technique because of its highly
      fenestrated endothelia and well-established disease models to manipulate the
      basement membrane charge barrier. After systemic injection of cationic or native
      ferritin (CF or NF) in rats, ex vivo and in vivo MRI showed selective
      accumulation of CF, but not NF, causing a 60% reduction in signal intensity in
      cortex at the location of individual glomeruli. Immunofluorescence and electron
      microscopy demonstrated that this CF accumulation was localized to the glomerular
      basement membrane (GBM). In a model of GBM breakdown during focal and segmental
      glomerulosclerosis, MRI showed reduced single glomerular accumulation of CF, but
      a diffuse accumulation of CF in the kidney tubules caused by leakage of CF
      through the glomerulus. Cationic contrast agents can be used to target the
      basement membrane and detect the breakdown of the basement membrane in disease.

PMID- 18727042
TI  - High spectral and spatial resolution MRI of age-related changes in murine
      prostate.
AB  - The purpose of this work was to evaluate high-resolution echo-planar
      spectroscopic MRI of normal and precancerous prostatic changes in a transgenic
      mouse line. Simian virus large T-antigen transgenic male mice (N = 7, age = 34 +/
      3.7 weeks) with prostatic hyperplasia and intraepithelial neoplasia (PIN) were
      studied. High spectral and spatial resolution (HiSS) MRI of the water proton
      signal was compared to the free induction decay (FID) integral image and
      conventional gradient-echo and spin-echo imaging. Water peak-height images of the
      prostate produced from HiSS datasets showed improved contrast-to-noise ratio
      (CNR) (P < 0.03), and greater morphological detail (P < 0.004) based on texture
      analysis. Despite the high spectral resolution of the HiSS datasets, signal-to
      noise ratio (SNR) compared favorably with that of the FID integral and
      conventional images. Lobular features in HiSS images of older mice were
      consistent with hyperplasia seen on histology. A partially deuterated water
      filled catheter was inserted in the mouse rectum for susceptibility matching
      between the colon interior and exterior to minimize image artifacts. These
      preliminary results suggest that HiSS MRI provides detailed morphology of the
      murine prostate and can detect early changes associated with the development of
      cancer. HiSS MRI of patients may have similar advantages.

PMID- 18727043
TI  - Biglycan overexpression on tooth enamel formation in transgenic mice.
AB  - Previously, it was shown that the volume of forming enamel of molar teeth in
      biglycan-null mice was greater than that in genetically matched wild-type mice.
      This phenotypic change appeared to result from an increase in amelogenin
      expression, implying that biglycan directly influences amelogenin synthesis. To
      determine whether biglycan overexpression resulted in decreased amelogenin
      expression, we engineered transgenic mice to overexpress biglycan in the enamel
      organ epithelium. Biglycan overexpression did not significantly affect the
      amelogenin expression in incisor and molar teeth in 3-day postnatal transgenic
      mice. In the transgenic animals, we observed that the immature and mature enamel
      appeared normal. These results suggested that increasing the biglycan expression,
      in the cells that synthesize the precursor protein matrix for enamel, has a
      negligible influence on amelogenesis.

PMID- 18727044
TI  - Effects of pre or posttraining dorsal hippocampus D-AP5 injection on fear
      conditioning to tone, background, and foreground context.
AB  - NMDA receptor antagonist D-AP5 was injected into the dorsal hippocampus of Wistar
      rats before or immediately after the training session in fear conditioning.
      Training was conducted both with signaled (background context) or unsignaled
      (foreground context) footshocks. Contextual fear conditioning was assessed 24 h
      later and tone fear conditioning 48 h after training (only in the signaled
      footshock condition). Pretraining injections impaired conditioned fear to
      contextual features, both in background and foreground configurations, whereas
      tone fear conditioning was left intact. Posttraining injections were ineffective
      in all cases. We conclude that dorsal hippocampal NMDA receptors are required for
      contextual fear acquisition independently of context saliency and that they are
      not required to early consolidation processes.

PMID- 18727045
TI  - Hippocampal levels of phosphorylated protein kinase A (phosphor-S96) are linked
      to spatial memory enhancement by SGS742.
AB  - Cognitive enhancement by the GABA (B) receptor antagonist SGS742 has been well
      documented, but mechanisms of action are not fully elucidated. Previous work has
      proposed involvement of somatostatin-14 and protein kinase C in cognitive
      enhancement; phospho-protein kinase A (p-PKA), fyn, and phospho-fyn are known
      signaling systems for spatial memory. It was the aim of the study to determine
      hippocampal levels of these proteins following SGS742-treatment and to correlate
      them with the outcome from the Morris water maze (MWM), represented by the
      parameter "time spent in the target quadrant" during the probe trial. OF1 mice
      were used for the experiments and divided into four groups: intraperitoneal
      SGS742 and saline solution treatment, both, tested in the MWM, and two yoked
      controls. Six hours following the probe trial, hippocampal protein levels were
      determined by immunoblotting. In the MWM, time spent in the target quadrant was
      significantly enhanced by SGS742 treatment. p-PKA levels were significantly
      increased only in the SGS742-treated group tested in the MWM as compared to
      saline treatment. In yoked controls, no significant differences in p-PKA levels
      between SGS742 and saline treatment were observed. Somatostatin-14 levels were
      significantly increased in both SGS742-treated groups. No statistically
      significant changes of other protein levels were observed. We propose that GABA
      (B) antagonism represented by SGS742 treatment led to cognitive enhancement
      involving p-PKA, because yoked controls treated with SGS742 were comparable to
      yoked saline-treated controls. The finding that somatostatin-14 was also induced
      in the SGS742-treated yoked controls points to a drug side effect, and therefore
      the role of somatostatin-14 for cognitive enhancement remains open.

PMID- 18727046
TI  - Spatial memory and the monkey hippocampus: not all space is created equal.
AB  - Studies of the role of the monkey hippocampus in spatial learning and memory,
      however few, have reliably produced inconsistent results. Whereas the role of the
      hippocampus in spatial learning and memory has been clearly established in
      rodents, studies in nonhuman primates have made a variety of claims that range
      from the involvement of the hippocampus in spatial memory only at relatively
      longer memory delays, to no role for the hippocampus in spatial memory at all. In
      contrast, we have shown that selective damage restricted to the hippocampus (CA
      regions) prevents the learning or use of allocentric, spatial relational
      representations of the environment in freely behaving adult monkeys tested in an
      open-field arena. In this commentary, we discuss a unifying framework that
      explains these apparently discrepant results regarding the role of the monkey
      hippocampus in spatial learning and memory. We describe clear and strict criteria
      to interpret the findings from previous studies and guide future investigations
      of spatial memory in monkeys. Specifically, we affirm that, as in the rodent, the
      primate hippocampus is critical for spatial relational learning and memory, and
      in a time-independent manner. We describe how claims to the contrary are the
      result of experimental designs that fail to recognize, and control for,
      egocentric (hippocampus-independent) and allocentric (hippocampus-dependent)
      spatial frames of reference. Finally, we conclude that the available data
      demonstrate unequivocally that the central role of the hippocampus in
      allocentric, spatial relational learning and memory is conserved among
      vertebrates, including nonhuman primates.

PMID- 18727047
TI  - The protein kinase C phosphorylation site on GAP-43 differentially regulates
      information storage.
AB  - Protein kinase C (PKC) is known to regulate phosphorylation of substrates such as
      MARCKS, GAP-43, and the NMDA receptor, all of which have been linked to synaptic
      plasticity underlying information storage processes. Here we report on three
      transgenic mice isoforms differentiated both by mutation of the PKC site on GAP
      43 as well as by their performance in three learning situations: (1) a radial arm
      maze task, which evaluates spatial memory and its retention, (2) fear
      conditioning which assesses contextual memory, and (3) the water maze which also
      evaluates spatial memory and its retention. The present results show, for the
      first time to our knowledge, that the phosphorylation state of a single site on
      an identified brain growth- and plasticity-associated protein differentially
      regulates performance of three different memory-associated tasks.

PMID- 18727048
TI  - The human hippocampus at 7 T--in vivo MRI.
AB  - The human hippocampus plays a central role in various neuropsychiatric disorders,
      such as temporal lobe epilepsy (TLE), Alzheimer's dementia, mild cognitive
      impairment, and schizophrenia. Its volume, morphology, inner structure, and
      function are of scientific and clinical interest. Magnetic resonance (MR) imaging
      is a widely employed tool in neuroradiological workup regarding changes in brain
      anatomy, (sub-) volumes, and cerebral function including the hippocampus. Gain in
      intrinsic MR signal provided by higher field strength scanners and concomitant
      improvements in spatial resolution seem highly valuable. An examination protocol
      permitting complete, high-resolution imaging of the human hippocampus at 7 T was
      implemented. Coronal proton density, T2, T2*, and fluid-attenuated inversion
      recovery contrasts were acquired as well as an isotropic 3D magnetization
      prepared rapid acquisition gradient-echo (500 microm isotropic voxel dimension,
      noninterpolated). Observance of energy deposition restrictions within acceptable
      scan times remained challenging in the acquisition of thin, spin-echo-based
      sections. At the higher resolution enabled by 7 T, demarcation of the hippocampus
      and some internal features including gray/white matter differentiation and
      depiction of the hippocampal mantle becomes much more viable when compared with
      1.5 T; thus, in the future, this imaging technology might help in the diagnosis
      of subtle hippocampal changes.

PMID- 18727049
TI  - Distinct hippocampal regions make unique contributions to relational memory.
AB  - Neuroscientific research has shown that the hippocampus is important for binding
      or linking together the various components of a learning event into an integrated
      memory. In a prior study, we demonstrated that the anterior hippocampus is
      involved in memory for the relations among informational elements to a greater
      extent that it is involved in memory for individual elements (Giovanello et al.,
      2004. Hippocampus 14:5-8). In the current study, we extend those findings by
      further specifying the role of anterior hippocampus during relational memory
      retrieval. Specifically, anterior hippocampal activity was observed during
      flexible retrieval of learned associations, whereas posterior hippocampal
      activity was detected during reinstatement of study episodes. These findings
      suggest a functional dissociation across the long axis of human hippocampus based
      on the nature of the mnemonic process rather than the stage of memory processing
      or type of stimulus.

PMID- 18727050
TI  - Modulation of AMPA receptor-mediated ion current by pituitary adenylate cyclase
      activating polypeptide (PACAP) in CA1 pyramidal neurons from rat hippocampus.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), a neurotrophic and
      neuromodulatory peptide, was recently shown to enhance NMDA receptor-mediated
      currents in the hippocampus (Macdonald, et al. 2005. J Neurosci 25:11374-11384).
      To check if PACAP might also modulate AMPA receptor function, we tested its
      effects on AMPA receptor-mediated synaptic currents on CA1 pyramidal neurons,
      using the patch clamp technique on hippocampal slices. In the presence of the
      NMDA antagonist D-AP5, PACAP (10 nM) reduced the amplitude of excitatory
      postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by stimulation of
      Schaffer collaterals. Following a paired-pulse stimulation protocol, the paired
      pulse ratio was unaffected in most neurons, suggesting that the AMPA-mediated
      EPSC was modulated by PACAP mainly at a postsynaptic level. PACAP also modulated
      the currents induced on CA1 pyramidal neurons by applications of either glutamate
      or AMPA. The effects of PACAP were dose-dependent: at a 0.5 nM dose, PACAP
      increased AMPA-mediated current; such effect was blocked by PACAP 6-38, a
      selective antagonist of PAC1 receptors. The enhancement of AMPA-mediated current
      by PACAP 0.5 nM was abolished when cAMPS-Rp, a PKA inhibitor, was added to the
      intracellular solution. At a 10 nM concentration, PACAP reduced AMPA-mediated
      current; such effect was not blocked by PACAP 6-38. The inhibitory effect of 10
      nM PACAP was mimicked by Bay 55-9837 (a selective agonist of VPAC2 receptors),
      persisted in the presence of intracellular BAPTA and was abolished by
      intracellular cAMPS-Rp. Stimulation-evoked EPSCs in CA1 neurons were
      significantly reduced following application of the PAC1 antagonist PACAP 6-38;
      this result indicates that PAC1 receptors in the CA1 region are tonically
      activated by endogenous PACAP and enhance CA3-CA1 synaptic transmission. Our
      results show that PACAP differentially modulates AMPA receptor-mediated current
      in CA1 pyramidal neurons by activation of PAC1 and VPAC2 receptors, both
      involving the cAMP/PKA pathway; the functional significance will be discussed in
      light of the multiple effects exerted by PACAP on the CA3-CA1 synapse at
      different levels.

PMID- 18727051
TI  - Fat-water separated delayed hyperenhanced myocardial infarct imaging.
AB  - Fat deposition associated with myocardial infarction (MI) has been reported as a
      commonly occurring phenomenon. Magnetic resonance imaging (MRI) has the ability
      to efficiently detect MI using T(1)-sensitive contrast-enhanced sequences and fat
      via its resonant frequency shift. In this work, the feasibility of fat-water
      separation applied to the conventional delayed hyperenhanced (DHE) MI imaging
      technique is demonstrated. A three-point Dixon acquisition and reconstruction was
      combined with an inversion recovery gradient-echo pulse sequence. This allowed
      fat-water separation along with T(1) sensitive imaging after injection of a
      gadolinium contrast agent. The technique is demonstrated in phantom experiments
      and three subjects with chronic MI. Areas of infarction were well defined as
      conventional hyperenhancement in water images. In two cases, fatty deposition was
      detected in fat images and confirmed by precontrast opposed-phase imaging.

PMID- 18727053
TI  - Sources of hepatic glucose production by 2H2O ingestion and Bayesian analysis of
      2H glucuronide enrichment.
AB  - The contribution of gluconeogenesis to hepatic glucose production (GP) was
      quantified after (2)H(2)O ingestion by Bayesian analysis of the position 2 and 5
      (2)H-NMR signals (H2 and H5) of monoacetone glucose (MAG) derived from urinary
      acetaminophen glucuronide. Six controls and 10 kidney transplant (KTx) patients
      with cyclosporine A (CsA) immunosuppressant therapy were studied. Seven KTx
      patients were lean and euglycemic (BMI = 24.3 +/- 1.0 kg/m(2); fasting glucose =
      4.7 +/- 0.1 mM) while three were obese and hyperglycemic (BMI = 30.5 +/- 0.7
      kg/m(2); fasting glucose = 7.1 +/- 0.5 mM). For the 16 spectra analyzed, the mean
      coefficient of variation for the gluconeogenesis contribution was 10% +/- 5%.
      This uncertainty was associated with a mean signal-to-noise ratio (SNR) of 79:1
      and 45:1 for the MAG H2 and H5 signals, respectively. For control subjects,
      gluconeogenesis contributed 54% +/- 7% of GP as determined by the mean and
      standard deviation (SD) of individual Bayesian analyses. For the
      lean/normoglycemic KTx subjects, the gluconeogenic contribution to GP was 62% +/-
      7% (P = 0.06 vs. controls), while hyperglycemic/obese KTx patients had a
      gluconeogenic contribution of 68% +/- 3% (P < 0.005 vs. controls). These data
      suggest that in KTx patients, an increased gluconeogenic contribution to GP is
      strongly associated with obesity and hyperglycemia.

PMID- 18727052
TI  - Evaluation of lactate and alanine as metabolic biomarkers of prostate cancer
      using 1H HR-MAS spectroscopy of biopsy tissues.
AB  - The goal of this study was to investigate the use of lactate and alanine as
      metabolic biomarkers of prostate cancer using (1)H high-resolution magic angle
      spinning (HR-MAS) spectroscopy of snap-frozen transrectal ultrasound (TRUS)
      guided prostate biopsy tissues. A long-echo-time rotor-synchronized Carr-Purcell
      Meiboom-Gill (CPMG) sequence including an electronic reference to access in vivo
      concentrations (ERETIC) standard was used to determine the concentrations of
      lactate and alanine in 82 benign and 16 malignant biopsies (mean 26.5% +/- 17.2%
      of core). Low concentrations of lactate (0.61 +/- 0.28 mmol/kg) and alanine (0.14
      +/- 0.06 mmol/kg) were observed in benign prostate biopsies, and there was no
      significant difference between benign predominantly glandular (N = 54) and
      stromal (N = 28) biopsies between patients with (N = 38) and without (N = 44) a
      positive clinical biopsy. In biopsies containing prostate cancer there was a
      highly significant (P < 0.0001) increase in lactate (1.59 +/- 0.61 mmol/kg) and
      alanine (0.26 +/- 0.07 mmol/kg), and minimal overlap with lactate concentrations
      in benign biopsies. This study demonstrates for the first time very low
      concentrations of lactate and alanine in benign prostate biopsy tissues. The
      significant increase in the concentration of both lactate and alanine in biopsy
      tissue containing as little as 5% cancer could be exploited in hyperpolarized
      (13)C spectroscopic imaging (SI) studies of prostate cancer patients.

PMID- 18727054
TI  - Flow cytometric assessment of monocyte activation markers and circulating
      endothelial cells in patients with localized or metastatic breast cancer.
AB  - BACKGROUND: Monocyte activation in cancer patients may be reflective of
      anticancer activity. However, studies indicate that recruitment of macrophages
      can actually promote tumor growth and angiogenesis. Assessment of other
      microenvironmental cells such as circulating endothelial cells (CECs) may provide
      additional information regarding disease progression. The objective of this study
      was to assess monocyte activation and CECs in breast cancer patients and
      determine the potential clinical relevance during disease progression. METHODS:
      Patients (n = 41) with localized or metastatic breast cancer who were not
      currently receiving treatment were eligible for study inclusion. Peripheral blood
      was collected and analyzed by flow cytometry for monocyte activation (Leuko64
      assay kit), and for CECs (CD146(+)CD45(-) phenotype). RESULTS: Metastatic breast
      cancer patients demonstrated a higher monocyte CD64 index relative to normal
      donors and localized breast cancer patients (P < 0.05). Furthermore, breast
      cancer patients had a lower monocyte CD163 index relative to normal donors (P =
      0.008). Localized breast cancer patients demonstrated higher levels of
      CD146(+)CD45(-) cells CECs relative to metastatic breast cancer patients and
      normal donors. Within the localized breast cancer population, levels of
      CD146(+)CD45(-) cells increased with disease stage (P < 0.05). CONCLUSIONS: These
      results suggest that monocyte activation and CECs may play a role in breast
      cancer progression. We speculate that monocyte activation may reflect a reaction
      to metastatic cells and/or response to tissue damage caused by metastatic growth
      in distant organs. Furthermore, the observation that CECs increase with disease
      stage in localized breast cancer suggests that CECs could be a useful surrogate
      marker for disease progression in this patient population.

PMID- 18727055
TI  - Anatomy of smooth muscle cells in nonmalignant and malignant human prostate
      tissue.
AB  - Differently graded areas of human prostate adenocarcinoma were examined after
      Masson's trichrome staining or immunohistochemistry for smooth muscle alpha
      actin, type IV collagen and laminin. In addition, the ultrastructure of the
      prostatic smooth muscle cells (SMC) during glandular proliferation and epithelial
      invasion in selected tumors was studied. The SMC formed a thick layer below the
      epithelial structures in unaffected areas and were closely associated with each
      other in homotypic interactions. As the tumor grade increased, the SMC gradually
      lost interactions with each other and became atrophic. With the growth of the
      epithelial compartment, the SMC initially segregated to the tumor periphery and
      the intercellular spaces increased. In high grade tumors, the epithelial cancer
      cells invaded the spaces between the SMC. Immunohistochemical analysis of the
      basal membrane revealed increased disruption of the usually thick basal membrane,
      which became thinner and faintly stained with each of the antibodies used. We
      conclude that most SMC become atrophic following epithelial invasion in human
      tumors and that degradation of the basal membrane is an important factor in this
      process. At the ultrastructural level, different SMC phenotypes occur in
      prostatic tissues during epithelial invasion. Interconversion between these
      phenotypes is suggested and a probable relationship among them is proposed.

PMID- 18727056
TI  - Morphological variation in the allantoplacenta within the genus Mabuya (squamata:
      Scincidae).
AB  - The type IV allantoplacenta has been described for the New World tropical
      scincids lizards of the genus Mabuya; it possesses the greatest morphological
      complexity known among viviparous squamates. Although a common morphological
      pattern has been observed in the few species of this lineage in which the
      allantoplacental morphology has been studied, some morphological variations may
      be present among species and populations. Here, we report morphological variation
      of the allantoplacenta of twelve populations of the genus Mabuya distributed in
      different geographical areas in northern South America using light microscopy. It
      is found that all the populations/species conserve a general arrangement of the
      placental structures. In the embryonic hemisphere there are a placentome,
      paraplacentome, and chorionic areolas; these structures are related to
      histotrophic nutrition. At the abembryonic hemisphere, there are absorptive
      plaques for histotrophic transfer and respiratory segments for gas exchange.
      However, in some populations some distinctive features in the placentome were
      found. The presence in the uterine syncytium of non syncytialized columnar cell
      groups, and invasive cells and apical projections of the chorionic cells directed
      toward the uterine syncytium, constitute a localized endotheliochorial placenta.
      Likewise, variations found in the abembryonic region include a greater
      morphological complexity, such as the folded and delimited absorptive plaques,
      and highly folded regions at the abembryonic pole (folded respiratory segments
      integrated with folded absorptive plaques). These specializations allow a larger
      surface for the passage of nutrients and respiratory exchange. Replication and
      the regionalized differentiation of the absorptive plaques were probably
      instrumental in the emergence of specialized structures for nutrient transport
      such as the placentome and the different types of absorptive plaques. These
      developmental processes appear to underlie the evolution of the placental
      complexity within thegenus Mabuya by the morphological variation of serial
      homologous structures.

PMID- 18727057
TI  - Correlation and immunolocalization of substance P nerve fibers and activated
      immune cells in human chronic gastritis.
AB  - Neuropeptides are able to modulate cytokine production by macrophages in response
      to various stimulators and have a major role in inflammation of different organs.
      Mammalian poly (ADP-ribose) polymerase (PARP) and nuclear factor kappa B (NF
      kappaB) both have been suggested to play a crucial role in inflammatory
      disorders. Unregulated increase of tumor necrosis factor-alpha (TNF-alpha) may
      also be pathogenic in inflammatory diseases. The aim of this study was to
      investigate the correlation between the number of Substance P (SP) containing
      nerve fibers and activated immune cells using immunohisto-, immunocytochemical
      (EM) and confocal laser microscopic methods. To investigate expression and
      activation of immune cells gastric biopsy samples from patients with chronic
      gastritis were used. The number of SP containing nerve fibers and activated
      immune cells increased significantly in gastritis. Using monoclonal p65 antibody,
      activated NF-kappaB was found in inflamed mucosa but was absent in uninflamed
      mucosa. Immunobinding for the activated form of p65 of NF-kappaB was found in 22%
      of macrophages and 45% of lymphocytes. The number of immune cells showing IR for
      NF-kappaB, PARP and TNF-alpha correlated with the increasing number of SP
      containing fibres. Confocal laser microscopy was used to confirm the
      colocalization of SP in TNF-alpha and NFkappaB positive lymphocytes and mast
      cells in inflamed mucosa. Immunoelectronmicroscopic investigation confirmed that
      these cells belong to lymphocytes, mast cells and macrophages. CONCLUSIONS: The
      increase of SP in nerve fibers and in activated immune cells further activate the
      production of other proinflammatory mediators (e.g. TNF-alpha) and therefore
      generate the chronic inflammation.

PMID- 18727058
TI  - Kinetics of H2AX phosphorylation after exposure to cisplatin.
AB  - BACKGROUND: Cisplatin is a widely used cancer chemotherapeutic drug that causes
      DNA crosslinking and stimulates H2AX phosphorylation. Our goal was to assess the
      potential of gammaH2AX to help predict tumor response to cisplatin treatment.
      METHODS: The kinetics of cisplatin-induced DNA interstrand crosslinks was
      measured using the alkaline comet assay and compared with gammaH2AX formation and
      clonogenic cell survival in several DNA repair proficient or deficient human and
      rodent cell lines. RESULTS: The comet assay was effective in ranking cell lines
      according to their relative sensitivity to cisplatin based on reduced crosslink
      formation measured 6 h after drug exposure or by the failure of irs3 and UV41
      cell lines to subsequently remove crosslinks. In comparison, the initial rate of
      phosphorylation of H2AX measured over the first 6 h after cisplatin treatment was
      unrelated to drug sensitivity or crosslinking proficiency. However, for
      proliferating cell cultures, the fraction of cells that retained gammaH2AX foci
      24 h after cisplatin treatment was correlated with the fraction of cells that
      lost clonogenic potential (slope = 1.1, r(2) = 0.85). CONCLUSIONS: H2AX
      phosphorylation occurs in response to replication fork damage caused by cisplatin
      induced DNA lesions, probably interstrand crosslinks. Although early kinetics of
      gammaH2AX formation was uninformative, retention of gammaH2AX foci 24 h after
      treatment was shown to be a useful indicator of cell response to killing by
      cisplatin. However, for gammaH2AX to serve as an indicator of cell viability
      after cisplatin treatment, cells must have the opportunity to transit S phase
      during the recovery period.

PMID- 18727060
TI  - A flow-cytometry method for analyzing the composition of membrane rafts.
AB  - Membrane rafts are involved in a broad variety of biological processes. Their
      protein composition under growth factor stimulation, anti-inflammatory or
      proinflammatory microenvironments, or in the course of pathogenic infections
      still remains to be determined. However, current techniques aimed at the
      identification of particular proteins on membrane rafts are not devoid of
      pitfalls. Membrane rafts were obtained by detergent-free based differential
      centrifugation from Jurkat T cells and J774 macrophages. Membrane rafts were
      labeled with fluorochrome-labeled antibodies directed against different cell
      membrane molecules, and with fluorochrome-labeled cholera toxin B that targets
      GM1 and analyzed by flow cytometry. CD3, CD11a, and GM1 were shown to be
      differentially expressed on Jurkat T cell-derived membrane rafts, indicating
      heterogeneity in membrane rafts composition. On the other hand, it was shown in
      J774 cell-derived membrane rafts that most but not all CD14 is present in the GM1
      containing membrane fragments, thus confirming the heterogeneity of membrane
      rafts composition in other cell lines. The method described here allows the
      fluorometric assessment of the relative expression of more than one membrane raft
      component at a time, and at a single vesicle level in a fast and sensitive
      manner. This method seems to be a suitable approach to evaluate the molecular
      heterogeneity in membrane rafts composition.

PMID- 18727061
TI  - Contamination of synthetic HuD protein spanning peptide pools with a CMV-encoded
      peptide.
AB  - To detect HuD-specific T cells in patients with Hu-antibody associated
      paraneoplastic neurological syndromes (Hu-PNS), we used short-term stimulation
      assays with HuD protein spanning peptide pools (PSPP) with purities of at least
      70% and found reproducible false-positive CD8+ T-cell responses in three of 127
      individuals (two healthy controls and one Hu-PNS patient), which all shared HLA
      A*2402 and HLA-B*1801. After testing the 15-mer peptides of the HuD antigen
      separately, we discovered that the same three 15-mers yielded the CD8+ T cell
      response in those three individuals. This highly unusual result could not be
      reproduced when using new batches of peptides with a higher level of purity (>82%
      and >95%). Therefore, we assumed this response was not directed against the HuD
      peptides and analyzed the HuD 15-mers by Fourier transform ion cyclotron
      resonance (FT-ICR) tandem mass spectrometry (MS/MS), which showed the presence of
      a cytomegalovirus (CMV)-encoded peptide (AIAEESDEEEAIVAY) as a contaminant. The
      three responding individuals all were CMV-seropositive and the contaminating
      peptide appeared to fit in the binding groove of HLA-B*18. Our data reveal that
      synthetic PSPP may contain immunogenic contaminations which may cause false
      positive results in T-cell stimulation assays.

PMID- 18727062
TI  - Diagnosing left ventricular noncompaction by echocardiography and cardiac
      magnetic resonance imaging and its dependency on neuromuscular disorders.
AB  - BACKGROUND: Left ventricular hypertrabeculation (LVHT), also termed noncompaction
      LVHT, is diagnosed by echocardiography or cardiac magnetic resonance imaging
      (CMRI), and associated with neuromuscular disorders (NMD). The aim of this study
      was to assess if LVHT can be diagnosed by CMRI applying echocardiographic
      definitions. METHODS AND RESULTS: The CMRI images of 19 echocardiographically
      diagnosed LVHT patients were re-evaluated (10 female, 14-67 y of age). Left
      ventricular hypertrabeculation was diagnosed by CMRI in 9 cases. Patients with
      CMRI-diagnosed LVHT were more often females (67% versus 40%), experienced heart
      failure more often (100% versus 50%), had an LV end diastolic diameter > 57 mm
      (67% versus 40%), had an LV fractional shortening < 25% (89% versus 40%), and had
      a larger extension of LVHT than patients without CMRI-diagnosed LVHT. The
      prevalence of NMD (87%) did not differ between both groups. CONCLUSIONS:
      Echocardiographic definition for CMRI yielded the diagnosis of LVHT in only 47%.
      When looking for LVHT by CMRI, LV size, function, and extension of LVHT have to
      be considered.

PMID- 18727063
TI  - Epidemiology of heart failure in a tertiary pediatric center.
AB  - BACKGROUND: In contrast to the adult age group, epidemiologic studies on heart
      failure (HF) in the pediatric population are lacking. The aim of this prospective
      study was to analyze the epidemiology of HF during infancy and childhood.
      METHODS: Of the 1,196 children with congenital and acquired heart diseases,
      primarily diagnosed during a 10-y period in one hospital, we identified those
      patients who developed HF. RESULTS: Within 10 y, 1,196 children with heart
      disease were indexed. Heart failure occurred in 124 of these patients (10.4%): 64
      out of 1,031 children with congenital heart diseases (6.2%), 13 out of 96
      children with rhythm or conduction disturbances (13.5%), 23 out of 39 children
      with acquired heart diseases (59.0%), and 24 out of 30 children with
      cardiomyopathies (80.0%). Heart failure occurred in 72 cases (58.1%) during the
      first year of life. The incidence in infancy was much more pronounced for
      congenital heart diseases than for other cardiac conditions. The mortality
      associated with HF and its cause was also lower for children with congenital
      heart disease (4.7%) than for the other cardiac conditions (8.7%, 23.0%, and
      25.0%, for acquired heart diseases, rhythm disturbances, and cardiomyopathies,
      respectively). CONCLUSION: Clear differences exist between HF in infants and HF
      in children. Our study supports the observation that congenital heart disease is
      the most common causative factor of HF during infancy. Older children with HF are
      more likely to have acquired heart diseases, cardiomyopathies, and arrhythmias,
      and these conditions have a considerable mortality.

PMID- 18727065
TI  - Simultaneous flow cytometric detection of basophil activation marker CD63 and
      intracellular phosphorylated p38 mitogen-activated protein kinase in birch pollen
      allergy.
AB  - BACKGROUND: Phosphorylation of p38 MAPK is a crucial step in IgE-receptor
      signaling in basophils. The relation of p38 MAPK to the well-validated diagnostic
      cell surface marker CD63 has not been evaluated in a clinical allergy model.
      METHODS: Expression of CD63 and phosphorylation of p38 MAPK were analyzed flow
      cytometrically in anti-IgE-gated basophils from 18 birch pollen allergic
      patients, five grass pollen allergic patients, and five healthy individuals,
      after 3 and 20 min of stimulation with recombinant major birch pollen allergen
      (rBet v 1). Additional time points and the influence of p38 MAPK inhibitor
      SB203580 were studied in birch pollen allergic patients. RESULTS: Phospho-p38
      MAPK and CD63 were expressed dose-dependently in birch pollen allergic patient
      basophils within 1 minute of rBet v 1 stimulation. P38 MAPK phosphorylation was
      fastest and subsided gradually while CD63 expression remained elevated for at
      least 20 min. Inhibition of p38 MAPK significantly inhibited CD63 upregulation.
      With optimal stimulation of the cells (1 MUg/mL), sensitivity and specificity for
      the discrimination between patients and a group of control individuals (grass
      pollen allergic patients and healthy controls) were 94% and 100% for CD63 at 3
      and 20 min and for phospho-p38 MAPK at 3 min. CONCLUSION: Antigen-induced p38
      MAPK phosphorylation in human basophils essentially contributes to CD63
      upregulation. It is a sensitive and specific intracellular marker for allergy
      diagnosis and offers new insight into the mechanisms of basophil activation.

PMID- 18727068
TI  - The use of receiver operating characteristic analysis for detection of minimal
      residual disease using five-color multiparameter flow cytometry in acute myeloid
      leukemia identifies patients with high risk of relapse.
AB  - BACKGROUND: Multiparameter flow cytometry (MFC) has been shown to be a useful
      approach for detection of minimal residual disease (MRD). The aim of the study
      was to determine the optimal threshold that can separate patients into two groups
      in terms of leukemic residual cells and relapse status after induction and
      consolidation chemotherapy. METHODS: Five-color MFC and receiver operating
      characteristics (ROC) analysis were used to determine the optimal threshold. This
      study analyzed 54 acute myeloid leukemia (AML) patients. RESULTS: LAPs were
      detected in 51/54 (94%) patients. MRD was evaluated in the bone marrow (BM) in
      morphologic complete remission from 25 and 22 patients after induction and
      consolidation, respectively. The threshold discriminating MRD(-) from MRD(+)
      cases was set at 0.15% residual leukemic cells, a level that allowed optimal
      sensitivity and specificity for prediction of relapse, both at postinduction (P =
      0.05) and postconsolidation (P = 0.009) time points using ROC analysis. MRD level
      postinduction not only influenced relapse-free survival (RFS) (P = 0.004) but
      also overall survival (OS) (P = 0.003). Multivariate analysis showed that MRD
      level postinduction was a powerful independent prognostic factor for both RFS (P
      = 0.037) and OS (P = 0.026). CONCLUSIONS: Using the ROC analysis, the threshold
      of 0.15% was defined as the optimal value in discriminating risk categories in
      AML, and postinduction MRD assessment is able to better predict disease outcome
      than consolidation. Therefore, MRD analysis by MFC could be used for refining the
      selection of therapeutic strategies and improving clinical outcome in individual
      patients.

PMID- 18727069
TI  - Mini-issue on primary cilia in bone and cartilage: preface to presentations from
      the Sun Valley Hard Tissue Workshop, August 2007.

PMID- 18727071
TI  - The primary cilium of connective tissue cells: imaging by multiphoton microscopy.
AB  - Although the role of the primary cilium as a sensory organelle in epithelial
      cells has been elucidated significantly over the past decade, the function of
      primary cilia in connective tissue cells has been studied less extensively.
      Primary cilia have been implicated as mechanotransducers in connective tissues,
      but the mechanisms by which the cells sense loads and convert them to biochemical
      signals for tissue formation and adaptation are poorly understood. Before
      hypotheses regarding the function of the primary cilium in connective tissue
      cells can be tested, methods for quantitation of incidence as well as three
      dimensional visualization of primary cilia with respect to the extracellular
      matrix (ECM) are needed. The objective of this study was to develop a rapid
      method for visualizing primary cilia in their native ECM in a wide range of
      connective tissues. Whole-mount immunohistochemical and multiphoton microscopy
      techniques were developed to simultaneously image primary cilia, cell nuclei, and
      collagen and their relationships to each other in situ. Axonemes of primary cilia
      projecting into the ECM were successfully visualized in thick sections of growth
      plate cartilage, tendon, ligament, meniscus, intervertebral disc, and
      perichondrium. These methodologies will allow analysis of the incidence and three
      dimensional orientation of primary cilia and enable investigation of the role of
      primary cilia in normal and pathological growth and adaptation in a variety of
      musculoskeletal tissues.

PMID- 18727072
TI  - Flow cytometric detection of erythrocyte osmotic fragility.
AB  - BACKGROUND: Hereditary spherocytosis (HS) is the most common cause of inherited
      chronic hemolysis. The various tests developed for HS screening have many
      shortcomings. The purpose of this study was to develop a new, simple, reliable
      test using flow cytometry. METHODS: In this new test, deionized water, a
      hemolysis-inducing agent, is spiked to a red cell suspension during acquisition,
      and the count of red cells is measured sequentially in real-time using flow
      cytometry. In this study, the optimal parameters for this test were established,
      and the discriminatory power of the adopted protocol was verified among several
      groups with various degrees of osmotic fragility (OF). RESULTS: The established
      protocol successfully discriminated between blood analyzed immediately and blood
      stored for 24 h (P < 0.00001). With healthy individuals as a reference, the OF
      measured by this protocol was significantly decreased in patients with iron
      deficiency anemia (P = 0.030) and was significantly increased in HS patients (P =
      1.1 x 10(-9)). This new test found all 11 HS patients to have increased OF.
      CONCLUSIONS: This new test was verified to be simple, quantitative, objective,
      and cost-effective for the measurement of OF. We suggest this test as another
      effective approach for HS screening, although its assay performance will require
      further verification through more clinical trials.

PMID- 18727075
TI  - Teratogenic effect of lithium carbonate in early development of BALB/c mouse.
AB  - Lithium carbonate is used as a standard treatment for manic depression. While
      researchers have investigated the teratogenic effects of lithium carbonate on
      embryos of various animals in later stages of development, very limited work has
      been done on the probability of effects at early stages of development. In this
      study, the teratogenic effect of lithium carbonate was investigated at earlier
      preimplantation through implantation stages of development of Balb/C mouse
      embryos. A therapeutic dose (i.e., 300 mg/kg b.w.) was injected into mice
      intraperitoneally on days 3.5, 4.5, 5.5, and 6.5 of pregnancy. Then, on day 15.5
      of gestation, embryos were collected from the pregnant animals. Among the
      embryos, 71.7% were healthy, 10.7% resorbed, 3.1% showed lordosis, 8.1% were
      underdeveloped and 8.4% had eye malformations. Significant increases (P < 0.05)
      in the number of hepatic megakaryocytes and nucleated red cells were also
      observed among experimental embryos. Analysis of maternal serum proteins prepared
      from dissected animals showed a significant increase or decrease (P < 0.05) in
      the levels of serum proteins albumin, alpha2 globulin, beta globulin, and gamma
      globulin. This research on early developmental stages suggests that pregnant
      mothers need to be aware of possible teratogenic effects at early stages of
      pregnancy, although it has been thought that the egg envelope can prevent
      teratogens from entering. In this case, mothers may need to stop lithium
      carbonate treatment before they make a decision to become pregnant.

PMID- 18727074
TI  - Primary cilia: cellular sensors for the skeleton.
AB  - The primary cilium is a solitary, immotile cilium that is present in almost every
      mammalian cell type. Primary cilia are thought to function as chemosensors,
      mechanosensors, or both, depending on cell type, and have been linked to several
      developmental signaling pathways. Primary cilium malfunction has been implicated
      in several human diseases, the symptoms of which include vision and hearing loss,
      polydactyly, and polycystic kidneys. Recently, primary cilia have also been
      implicated in the development and homeostasis of the skeleton. In this review, we
      discuss the structure and formation of the primary cilium and some of the
      mechanical and chemical signals to which it could be sensitive, with a focus on
      skeletal biology. We also raise several unanswered questions regarding the role
      of primary cilia as mechanosensors and chemosensors and identify potential
      research avenues to address these questions.

PMID- 18727076
TI  - In-stent restenosis in bare metal stents versus sirolimus-eluting stents after
      primary coronary intervention for acute myocardial infarction and subsequent
      transcoronary transplantation of autologous stem cells.
AB  - BACKGROUND: Following stenting for acute myocardial infarction, transcoronary
      transplantation of granulocyte-colony stimulating factor (G-CSF) mobilized
      autologous stem cells (ASC) has been shown to result in an increased in-stent
      restenosis rate of bare metal stents (BMS). HYPOTHESIS: This study sought to
      compare the extent of neointimal growth in BMS and sirolimus-eluting stents (SES)
      after primary implantation, and subsequent transcoronary transplantation of G-CSF
      mobilized stem cells. METHODS: Patients with stenting of the left anterior
      descending coronary artery for acute anterior myocardial infarction were randomly
      assigned to receive a BMS or SES. Intracoronary stem cell injection was performed
      after G-CSF application for at least 4 d and cell apheresis. The angiograms
      obtained after cell transplantation and after 6 mo were analyzed by quantitative
      coronary angiography. RESULTS: We performed primary stenting and stem cell
      transplantion in 16 patients who received a BMS (n = 8) or an SES (n = 8). In 2
      patients with a BMS, late stent thrombosis occurred after 58 d and 177 d,
      respectively. In the remaining patients, control angiography after 6 mo revealed
      in-stent restenosis of >50% in no patients with SES but in 4 patients with BMS
      (67%). Late lumen loss and in-stent plaque volume were significantly higher in
      patients with BMS compared with patients with SES. CONCLUSIONS: Compared with
      BMS, SES impair in-stent intima hyperplasia after stenting for acute myocardial
      infarction and transcoronary transplantation of G-CSF mobilized ASC.

PMID- 18727077
TI  - Lack of pathologic Q waves: a specific marker of viability in myocardial
      hibernation.
AB  - BACKGROUND: The present study evaluates the lack of Q waves on the
      electrocardiogram (ECG) in the prediction of myocardial viability compared with
      dobutamine stress echocardiography (DSE) and rest-redistribution thallium-201 (Tl
      201) scintigraphy. HYPOTHESIS: The lack of pathologic Q waves (NoQ) may be a
      readily available and specific marker for the presence of viability. METHODS:
      Sixty four patients with stable coronary artery disease (CAD) and ventricular
      dysfunction underwent rest ECG, DSE, and Tl-201 scintigraphy before
      revascularization, and a repeat rest 2-Dimensional (2-D) echocardiogram more than
      3 mo later. RESULTS: Total viability at baseline (% of total segments) was higher
      in the NoQ group by Tl-201 scintigraphy (87 +/- 19% versus 70 +/- 20%, p = 0.008)
      and by DSE (81 +/- 20% versus 65 +/- 24%, p = 0.013). As expected, the
      sensitivity of NoQ waves was low in predicting recovery of function (23%), and
      inferior to Tl-201 (82%) and DSE (84%) (p<0.08). However, specificity of NoQ
      waves for predicting recovery of global function was high (72%); higher than Tl
      201 (50%) and DSE (45%). Positive predictive values were comparable among all
      modalities. Results were similar if the data were analyzed regionally for
      viability. CONCLUSION: Lack of pathologic Q waves is a specific and readily
      available marker of myocardial viability in patients with chronic CAD, which
      should alert the clinician for myocardial hibernation.

PMID- 18727078
TI  - Utility of CD26 in flow cytometric immunophenotyping of T-cell lymphomas in
      tissue and body fluid specimens.
AB  - BACKGROUND: CD26 is expressed by most CD4+ T cells in normal peripheral blood
      specimens. Neoplastic T cells are frequently CD26- in mycosis fungoides/Sezary
      syndrome involving the peripheral blood. However, CD26 expression by reactive and
      neoplastic T cells in solid tissues and body fluids has not been fully
      characterized by flow cytometry (FC). METHODS: Solid tissue and body fluid
      specimens were assayed for CD26 expression using four-color FC immunophenotyping,
      by qualitative assessment of population clusters, and by quantitation with
      comparison with isotype controls. Benign T cells were studied in reactive tissues
      and in the background of other malignancies. RESULTS: Many T-cell lymphomas were
      dim or negative for CD26, whereas a few were brightly positive. In the majority
      of T-cell lymphomas, CD26 expression could potentially help identify aberrant
      population clusters. T cells in reactive tissue specimens and tumor-infiltrating
      T cells were commonly dim to negative for CD26. CONCLUSIONS: Both T-cell
      lymphomas and reactive T cells in tissue and body fluid specimens often show low
      levels of CD26 expression. Therefore, quantitative methods may not reliably
      distinguish benign from neoplastic T cells in these specimens. However, CD26, in
      combination with other T-cell markers, can be helpful for identifying aberrant
      population clusters in T-cell lymphomas.

PMID- 18727079
TI  - Rapid and accurate quantification of right ventricular volume and stroke volume
      by real-time 3-dimensional triplane echocardiography.
AB  - BACKGROUND: Previous studies have demonstrated that 3-Dimensional (3-D)
      echocardiography can determine right ventricular (RV) volume accurately. However,
      this technique has not been feasible in everyday clinical practice because of the
      necessity of time-consuming off-line processes. HYPOTHESIS: A newly developed
      real-time 3-D triplane echocardiography, which acquires 3 apical rotational cross
      sectional images simultaneously, holds the promise to resolve these problems.
      METHODS AND RESULTS: Sixteen excised formalin fixed porcine hearts and 24 healthy
      human subjects underwent real-time 3-D triplane echocardiography. In an anatomic
      in vitro study, the actual volume of RV was obtained by spilling water in the RV
      cavity into a graduated cylinder for measurement, which served as a reference
      standard for comparison. For healthy subjects, the RV stroke volume (SV) was
      measured by triplane echocardiography which was compared with the left
      ventricular (LV) SV obtained by conventional 2-Dimensional echocardiography (2
      DE). Excellent correlation and agreement between 3-D triplane imaging derived RV
      volume and the actual one for excised porcine hearts were observed (r = 0.979, p
      < 0.001, mean difference 2.2 mL). In healthy human subjects, good correlation and
      agreement between 3-D triplane imaging derived RV SV and LV SV measured by 2-DE
      were obtained (r = 0.970, p < 0.001, mean difference 5.9 mL). CONCLUSIONS: Real
      time 3-D triplane echocardiography provides us a new method for rapid and
      accurate quantification of RV volume. Furthermore, this new method holds the
      promise for evaluating RV volume and SV in routine clinical practice.

PMID- 18727080
TI  - Inferring multiple maxima in intravoxel white matter fiber distribution.
AB  - A new methodology is introduced that characterizes the intravoxel orientation
      distribution function (ODF) based on a single-fiber model of the diffusion MRI
      signal. Using a Bayesian framework the probability of finding a fiber in a
      specific orientation is obtained. The proposed ODF estimation relies on a cigar
      like diffusion tensor model, the methodology is thus denominated Bayesian cigar
      like diffusion tensor (BCDT). This work makes two major contributions: 1) the
      study of single-fiber models in detecting fibers with different volume fractions
      in a voxel, and 2) the introduction of the Nth-root correction to improve the
      detection of fibers with smaller volume fractions, where N is the number of
      diffusion MRI measurements. It is demonstrated that the incomplete signal
      modeling fails to reconstruct the relative fiber volume fractions, especially
      when the intravoxel diffusion profiles have dissimilar contributions to the
      diffusion MRI signal. In this situation the fibers with smaller contributions are
      hardly detectable. The BCDT method proposed here reduces this effect by
      introducing the Nth-root correction, making multiple fibers estimable. The
      performance of the new methodology is illustrated using synthetic and real data,
      as well as the data from a phantom of intersecting capillaries.

PMID- 18727081
TI  - Balanced left ventricular myocardial SSFP-tagging at 1.5T and 3T.
AB  - The purpose of the study was to evaluate the performance of steady-state free
      precession (SSFP)-tagging at 1.5T and 3T and to define the ideal settings with
      respect to optimized tag contrast throughout the cardiac cycle for both field
      strengths. To identify optimal imaging parameters data acquisition was repeated
      for different flip angles. Left ventricular tag-tissue contrast, tag fading
      times, tag persistence, and myocardial signal-to-noise ratio (SNR) were
      quantified in basal, mid-ventricular, and apical slice locations. To assess the
      effect of field strength on image quality and artifact level, additional
      semiquantitative image grading was performed by two experienced readers. SSFP
      tagging at 3T proved superior to 1.5T and provided significantly enhanced tag
      persistence and myocardial SNR while maintaining overall image quality and
      artifact level. The definition of a tag quality index demonstrated optimal SSFP
      tagging performance for a flip angle of 20 degrees . Diastolic tag visibility was
      improved at 3T and resulted in enhanced average tag persistence of 789 +/- 128 ms
      compared to 523 +/- 40 ms at 1.5T. For SSFP-tagging at 3T the combination of T(1)
      lengthening and superior myocardial SNR is highly promising and has the potential
      to improve the depiction of tagged myocardial function throughout the entire
      cardiac cycle.

PMID- 18727082
TI  - Effects of refocusing flip angle modulation and view ordering in 3D fast spin
      echo.
AB  - Recent advances have reduced scan time in three-dimensional fast spin echo (3D
      FSE) imaging, including very long echo trains through refocusing flip angle (FA)
      modulation and 2D-accelerated parallel imaging. This work describes a method to
      modulate refocusing FAs that produces sharp point spread functions (PSFs) from
      very long echo trains while exercising direct control over minimum, center-k
      space, and maximum FAs in order to accommodate the presence of flow and motion,
      SNR requirements, and RF power limits. Additionally, a new method for ordering
      views to map signal modulation from the echo train into k(y)-k(z) space that
      enables nonrectangular k-space grids and autocalibrating 2D-accelerated parallel
      imaging is presented. With long echo trains and fewer echoes required to encode
      large matrices, large volumes with high in- and through-plane resolution matrices
      may be acquired with scan times of 3-6 min, as demonstrated for volumetric brain,
      knee, and kidney imaging.

PMID- 18727083
TI  - Comparison of parallel MRI reconstruction methods for accelerated 3D fast spin
      echo imaging.
AB  - Parallel MRI (pMRI) achieves imaging acceleration by partially substituting
      gradient-encoding steps with spatial information contained in the component coils
      of the acquisition array. Variable-density subsampling in pMRI was previously
      shown to yield improved two-dimensional (2D) imaging in comparison to uniform
      subsampling, but has yet to be used routinely in clinical practice. In an effort
      to reduce acquisition time for 3D fast spin-echo (3D-FSE) sequences, this work
      explores a specific nonuniform sampling scheme for 3D imaging, subsampling along
      two phase-encoding (PE) directions on a rectilinear grid. We use two
      reconstruction methods-2D-GRAPPA-Operator and 2D-SPACE RIP-and present a
      comparison between them. We show that high-quality images can be reconstructed
      using both techniques. To evaluate the proposed sampling method and
      reconstruction schemes, results via simulation, phantom study, and in vivo 3D
      human data are shown. We find that fewer artifacts can be seen in the 2D-SPACE
      RIP reconstructions than in 2D-GRAPPA-Operator reconstructions, with comparable
      reconstruction times.

PMID- 18727084
TI  - Prospective self-gating for simultaneous compensation of cardiac and respiratory
      motion.
AB  - Segmented cardiac acquisitions generally require the use of an electrocardiogram
      (ECG) in combination with a breathhold or a respiratory navigator placed on the
      diaphragm. These techniques necessitate patient cooperation and increase the
      complexity of cardiac imaging. The ECG signal may be distorted inside the magnet
      by interferences from radiofrequency and gradient action. Breathhold acquisition
      limits the total scan time, while navigators on the diaphragm might not fully
      reflect respiratory-induced motion of the heart. To overcome some of these
      problems, several self-gating (SG) or "wireless" techniques have recently been
      presented. All of these approaches, however, are based on either cardiac
      triggering or respiratory gating, or the data are processed retrospectively,
      reducing the efficiency of data acquisition. In this work a prospective SG
      approach for free-breathing imaging is presented that requires neither ECG gating
      nor respiratory navigation. The motion data used for cardiac triggering and
      respiratory gating are extracted from the repeatedly acquired k-space center.
      Based on computer simulations and in vivo data of the heart, it is shown that
      cardiac as well as respiratory motion can be accurately extracted in real time.
      Using the method proposed, the scan efficiency could be significantly increased
      while preserving image quality relative to retrospective SG approaches.

PMID- 18727085
TI  - Quantitative magnetization transfer imaging using balanced SSFP.
AB  - It is generally accepted that signal formation in balanced steady-state free
      precession (bSSFP) is a simple function of relaxation times and flip angle only.
      This can be confirmed for fluids, but for more complex substances, magnetization
      transfer (MT) can lead to a considerable loss of steady-state signal. Thus,
      especially in tissues, the analytical description of bSSFP requires a revision to
      fully take observed effects into account. In the first part of this work, an
      extended bSSFP signal equation is derived based on a binary spin-bath model.
      Based on this new model of bSSFP signal formation, quantitative MT parameters
      such as the fractional pool size, corresponding magnetization exchange rates, and
      relaxation times can be explored. In the second part of this work, model
      parameters are derived in normal appearing human brain. Factors that may
      influence the quality of the model, such as B(1) field inhomogeneities or off
      resonances, are discussed. Overall, good correspondence between parameters
      derived from two-pool bSSFP and common quantitative MT models is observed. Short
      repetition times in combination with high signal-to-noise ratios make bSSFP an
      ideal candidate for the acquisition of high resolution isotropic quantitative MT
      maps, as for the human brain, within clinically feasible acquisition times.

PMID- 18727086
TI  - Strongly modulating pulses for counteracting RF inhomogeneity at high fields.
AB  - A new pulse technique for counteracting RF inhomogeneity at high fields is
      reported. The pulses make use of the detailed knowledge of the voxels' B(1) and
      B(0) amplitude 2D histogram to generate, through an optimization procedure, gates
      where the flip angle is made uniform. Although most approaches to date require
      the use of parallel transmission, this method does not and therefore offers
      several advantages. The data necessary for the algorithm to determine an
      irradiation scheme requires only one transmit B(1) along with a B(0)
      inhomogeneity measurement. The use of a B(1) and B(0) amplitude 2D histogram
      instead of their spatial distribution also decreases substantially the complexity
      of the optimization problem, allowing the algorithm to find an RF solution in
      less than 30 s. Finally, the optimization procedure is based on an exact
      calculation and does not use any linear approximation. In this article, the
      theory behind the method in addition to spoiled gradient echo experimental data
      at 3T for 3D brain imaging are reported. The images obtained yield a reduction of
      the standard deviation of the sine of the flip angle by a factor of up to 15
      around the desired value, compared to when a standard square pulse calibrated by
      the scanner is used.

PMID- 18727088
TI  - In vivo 1H NMR measurement of glycine in rat brain at 9.4 T at short echo time.
AB  - Glycine is an amino acid present in mammalian brain, where it acts as an
      inhibitory and excitatory neurotransmitter. The two detectable protons of glycine
      give rise to a singlet at 3.55 ppm that overlaps with the more intense myo
      inositol resonances, and its measurement has traditionally required specific
      editing efforts. The aim of the current study was to reduce the signal intensity
      of myo-inositol relative to that of glycine by exploiting the fast signal J
      evolution of the myo-inositol spin system when using a single spin-echo
      localization method we recently introduced. Glycine was detected at TE = 20 ms
      with an average Cramer-Rao lower bound (CRLB) of 8.6% +/- 1.5% in rat brain (N =
      5), at 9.4 T. The concentration of glycine was determined using LCModel analysis
      at 1.1 +/- 0.1 mM, in good agreement with biochemical measurements previously
      reported. We conclude that at high magnetic fields, glycine can be measured at a
      relatively short echo time (TE) without additional editing efforts.

PMID- 18727087
TI  - Functional colonography of Min mice using dark lumen dynamic contrast-enhanced
      MRI.
AB  - Dark lumen MRI colonography detects colonic polyps by minimization of the
      intestinal lumen signal intensity. Here we validate the use of perfluorinated oil
      as an intestinal-filling agent for dark lumen MRI studies in mice, enabling the
      physiological characterization of colonic polyps by dynamic contrast-enhanced
      MRI. In control and Min (multiple intestinal neoplasia) mice with and without
      pretreatment with oral dextran sodium sulfate (DSS), polyps as small as 0.94 mm
      diameter were consistently identified using standard 2D gradient echo imaging
      (voxel size, 0.23 x 0.16 x 0.5 mm). In serial studies, polyp growth rates were
      heterogeneous with an average approximately 5% increase in polyp volume per day.
      In DSS-treated control mice the colon wall contrast agent extravasation rate
      constant, K(trans), and extravascular extracellular space volume fraction, v(e),
      values were measured for the first time and found to be 0.10 +/- 0.03 min(-1) and
      0.23 +/- 0.09, respectively. In DSS-treated Min mice, polyp K(trans) values (0.09
      +/- 0.04 min(-1)) were similar to those in the colon wall but the v(e) values
      were substantially lower (0.16 +/- 0.03), suggesting increased cellular density.
      The functional dark-lumen colonography approach described herein provides new
      opportunities for the noninvasive assessment of gastrointestinal disease
      pathology and treatment response in mouse models.

PMID- 18727089
TI  - Multiple-profile homogeneous image combination: application to phase-cycled SSFP
      and multicoil imaging.
AB  - Signal inhomogeneities in MRI often appear as multiplicative weightings due to
      various factors such as field-inhomogeneity dependencies for steady-state free
      precession (SSFP) imaging or receiver sensitivities for coil arrays. These signal
      inhomogeneities can be reduced by combining multiple data sets with different
      weights. A sum-of-squares combination is typically used due to its simplicity and
      near-optimal signal-to-noise ratio (SNR). However, this combination may lead to
      residual signal inhomogeneity. Alternatively, an optimal linear combination of
      the data can be performed if the weightings for individual data sets are
      estimated accurately. We propose a nonlinear combination to improve image-based
      estimates of the individual weightings. The signal homogeneity can be
      significantly increased without compromising SNR. The improved performance of the
      method is demonstrated for SSFP banding artifact reduction and multicoil (phased
      array and parallel) image reconstructions.

PMID- 18727090
TI  - Rapid radiofrequency field mapping in vivo using single-shot STEAM MRI.
AB  - Higher field strengths entail less homogeneous RF fields. This may influence
      quantitative MRI and MRS. A method for rapidly mapping the RF field in the human
      head with minimal distortion was developed on the basis of a single-shot
      stimulated echo acquisition mode (STEAM) sequence. The flip angle of the second
      RF pulse in the STEAM preparation was set to 60 degrees and 100 degrees instead
      of 90 degrees , inducing a flip angle-dependent signal change. A quadratic
      approximation of this trigonometric signal dependence together with a calibration
      accounting for slice excitation-related bias allowed for directly determining the
      RF field from the two measurements only. RF maps down to the level of the medulla
      could be obtained in less than 1 min and registered to anatomical volumes by
      means of the T(2)-weighted STEAM images. Flip angles between 75% and 125% of the
      nominal value were measured in line with other methods.

PMID- 18727091
TI  - Cerebral blood flow MRI in mice using the cardiac-spin-labeling technique.
AB  - Continuous arterial spin labeling MRI with a separate neck labeling coil provides
      a highly sensitive method to image cerebral blood flow (CBF). In mice, however,
      this has not been possible because the proximity of the neck coil to the brain
      uses the neck coil to significantly saturate the brain signal. To overcome this
      limitation the cardiac spin labeling (CSL) technique is introduced in which the
      labeling coil is placed at the heart position. To demonstrate its utility, CSL
      CBF was applied to image quantitative basal CBF and hypercapnia-induced CBF
      changes. This approach provides a practical means to image CBF with high
      sensitivity in small animals, compares favorably to existing mouse CBF imaging
      techniques, and could broaden CBF applications in mice where many brain disease
      and transgenic models are widely available.

PMID- 18727092
TI  - Low dose beta-blocker prevents ovariectomy-induced bone loss in rats without
      affecting heart functions.
AB  - Findings from animal studies have suggested that bone remodeling is under beta
      adrenergic control. However, the level of adrenergic inhibition required to
      achieve the most favorable effects on the skeleton remains unknown. To address
      this question, we compared the effects of low (0.1 mg/Kg/day), medium (5
      mg/Kg/day) or high (20 mg/Kg/day) doses of propranolol given 5 days per week for
      10 weeks in ovariectomized (OVX) rats. Characteristics of bone microarchitecture,
      biomechanical properties and bone turnover were investigated, whilst heart
      functions were assessed by echocardiography and catheterization of the left
      ventricle. We first confirmed the expression of Adrbeta2R and the absence of
      Adrbeta1R on osteoblasts by PCR and confocal microscopy. We then showed that low
      dose propranolol prevented OVX induced bone loss by increasing bone formation
      (+30% of MAR vs. placebo, P = 0.01) and decreasing bone resorption (-52% of
      osteoclast surface on bone surface vs. placebo, P = 0.01). Consequently, rats
      receiving 0.1 mg/kg/day propranolol displayed higher stress (+27%), intrinsic
      energy (+28.7%) and Young's Modulus in compression versus placebo (all, P <
      0.05). No significant effects on heart hemodynamic parameters were found in rats
      receiving this dose. In contrast, medium and high doses of propranolol had a
      negative effect on heart functions but no significant protective effects on bone
      mass in ovariectomized rats. These results, consistent with the dominant nature
      of the high bone mass phenotype and normal heart function of Adrbeta2R-deficient
      mice, suggest that low doses of beta-blockers may have a therapeutic utility in
      the treatment of osteoporosis with high selectivity for bone tissues.

PMID- 18727093
TI  - Internalization of EGF receptor following lipid rafts disruption in keratinocytes
      is delayed and dependent on p38 MAPK activation.
AB  - The receptor for epidermal growth factor (EGF) plays an important role in
      epidermal keratinocytes and is known to move out of lipid raft after cholesterol
      depletion, leading to ligand-independent activation. Accumulation of evidence
      indicates the ability of EGF receptor (EGFR) to undergo internalization without
      participation of the ligand under the control of p38 MAPK during stress
      conditions. Since cholesterol depletion using methyl-beta-cyclodextrin is known
      to induce ligand-independent activation of EGFR in keratinocytes, we investigated
      by confocal microscopy and ligand-binding tests the processing and localization
      of EGFR following lipid raft disruption. Here, we report the dimerization and the
      slow internalization of the receptor accompanied by the delayed phosphorylation
      of tyrosine 1068 and its degradation by the proteasome. We also demonstrate the
      involvement of p38 MAPK during the process of internalization, which can be
      considered as a protective response to stress. Moreover, cholesterol-depleted
      keratinocytes recover their ability to proliferate during the recovery period
      that follows lipid raft disruption.

PMID- 18727094
TI  - Molecular cloning and characterization of a new gene, Oocyte-G1.
AB  - Oocytes are recognized as a source of regulatory molecules that influence
      follicular development through an array of actions on granulosa cells. Recently,
      more and more hormones and signaling molecules were identified during follicular
      developmental processes; however, the details about their functions are still
      unclear. During efforts to clone follicular development-related genes, we
      isolated a cDNA fragment by DDRT-PCR. To obtain cDNA 5'- and 3'-end sequences, we
      screened a mouse ovarian cDNA library. After screening the library, an open
      reading frame of 2,994 bp for the new gene (Oocyte-G1), which encodes a 997
      residue protein, was cloned. Northern blot analysis revealed the presence of
      approximately 3.6 kb Oocyte-G1 mRNA in ovary, lung, kidney, testis and brain.
      Northern analysis of RNA from ovaries in vivo showed that Oocyte-G1 was weakly
      expressed on day 5 and at a moderate level on day 10. Thereafter, on day 15 or in
      adults (day 40), there was an increase in expression, followed by a decline in
      ovaries on day 20 or older (day 120). Furthermore, we studied the Ooctye-G1
      protein by using the antiserum against a peptide sequence unique to this gene in
      Western blotting and immunolocalization. The antiserum recognized a prominent
      band of approximately 110 kDa in immunoblots and signals were dispersed in
      oocytes and some cumulus granulosa cells. Our results suggest the potential role
      of Oocyte-G1 in ovarian follicular development.

PMID- 18727095
TI  - Novel MRI method to detect altered left ventricular ejection and filling patterns
      in rodent models of disease.
AB  - The aim of this study was to determine whether high-temporal-resolution (HTR)
      cardiac cine-MRI could be used to identify subtle alterations in contractility
      and diastolic function in rodent models of disease. Following standard 45-min in
      vivo MRI measurements of left ventricular (LV) volumes, a single mid-ventricular
      slice was selected for 3-min HTR imaging. Cavity volume was measured every 2.4
      ms, yielding approximately 60 images through the cardiac cycle. From these
      images, peak ejection and filling rates were calculated and two separate filling
      phases (comparable with the early (E) and late (A) phases of a Doppler
      echocardiogram) were identified during diastole. Repeated HTR imaging of the same
      animals on sequential days indicated reproducibility of E'/A' ratios of 11%. In
      chronically infarcted rat hearts, HTR imaging revealed lower peak ejection rates
      (PERs), peak early filling rates (E') and E'/A' ratios, and higher peak late
      filling rates (A') than in sham-operated rats. Diabetic db/db mouse hearts had
      the same function as controls when using standard cine-MRI, yet HTR imaging
      identified significantly lower PERs, early filling rates and E'/A' ratios in
      diabetic mouse hearts. In conclusion, the HTR MRI technique revealed changes in
      function that were below the limits of detection of standard cine-MRI.

PMID- 18727096
TI  - Positive contrast visualization of nitinol devices using susceptibility gradient
      mapping.
AB  - MRI visualization of devices is traditionally based on signal loss due to T(2)*
      effects originating from local susceptibility differences. To visualize nitinol
      devices with positive contrast, a recently introduced postprocessing method is
      adapted to map the induced susceptibility gradients. This method operates on
      regular gradient-echo MR images and maps the shift in k-space in a (small)
      neighborhood of every voxel by Fourier analysis followed by a center-of-mass
      calculation. The quantitative map of the local shifts generates the positive
      contrast image of the devices, while areas without susceptibility gradients
      render a background with noise only. The positive signal response of this method
      depends only on the choice of the voxel neighborhood size. The properties of the
      method are explained and the visualizations of a nitinol wire and two stents are
      shown for illustration.

PMID- 18727097
TI  - Susceptibility gradient mapping (SGM): a new postprocessing method for positive
      contrast generation applied to superparamagnetic iron oxide particle (SPIO)
      labeled cells.
AB  - Local susceptibility gradients result in a dephasing of the precessing magnetic
      moments and thus in a fast decay of the NMR signals. In particular, cells labeled
      with superparamagnetic iron oxide particles (SPIOs) induce hypointensities,
      making the in vivo detection of labeled cells from such a negative image contrast
      difficult. In this work, a new method is proposed to selectively turn this
      negative contrast into a positive contrast. The proposed method calculates the
      susceptibility gradient and visualizes it in a parametric map directly from a
      regular gradient-echo image dataset. The susceptibility gradient map is
      determined in a postprocessing step, requiring no dedicated pulse sequences or
      adaptation of the sequence before and during image acquisition. Phantom
      experiments demonstrated that local susceptibility differences can be quantified.
      In vivo experiments showed the feasibility of the method for tracking of SPIO
      labeled cells. The method bears the potential also for usage in other
      applications, including the detection of contrast agents and interventional
      devices as well as metal implants.

PMID- 18727098
TI  - Image-based coronary tracking and beat-to-beat motion compensation: feasibility
      for improving coronary MR angiography.
AB  - A method to reduce the effect of motion variability in MRI of the coronary
      arteries is proposed. It involves acquiring real-time low-resolution images in
      specific orthogonal orientations, extracting coronary motion from these images,
      and then using this motion information to guide high-resolution MR image
      acquisition on a beat-to-beat basis. The present study establishes the
      feasibility and efficacy of the proposed approach using human motion data in an
      offline implementation, prior to future online implementation on an MRI scanner.
      To track the coronary arteries in low-resolution real-time MR images in an
      accurate manner, a tracking approach is presented and validated. The tracking
      algorithm was run on real-time images acquired at 15-20 frames per second in four
      chamber, short-axis, and coronal views in five volunteers. The systolic and
      diastolic periods in the cardiac cycles, computed from the extracted motion
      information, had significant variability during the short time periods typical of
      cardiac MRI. It is also demonstrated through simulation analysis using human
      tracked coronary motion data that accounting for this cardiac variability by
      adaptively changing the trigger delay for acquisition on a beat-to-beat basis
      improves overall motion compensation and hence MR image quality evaluated in
      terms of SNR and CNR values.

PMID- 18727099
TI  - Modeling SSFP functional MRI contrast in the brain.
AB  - Steady-state free precession (SSFP) has recently been proposed for function MRI
      because of the potential for reducing image distortion and signal dropout.
      Several different contrast mechanisms have been suggested to explain the reported
      observations, but there has been limited work comparing theory with experiment in
      the brain. Moreover, the detailed work that has considered oxygen-dependent
      signal in SSFP outside the brain has focused on R(2) effects in the pass band,
      and largely neglected the signal contrast that occurs due to off-resonance
      effects. The article describes a model for SSFP functional contrast based on the
      convolution of the theoretical SSFP profile with the underlying frequency
      distribution. It is demonstrated that such a model must account for the effects
      of diffusion, which can alter the apparent R(2) and linespread. Monte Carlo
      simulations are used to calibrate corrections for these terms. This new model has
      the computational efficiency of the convolution model while encapsulating
      information from more time-consuming Monte Carlo simulations. This corrected
      convolution model is shown to agree well with experimental data, and model
      predictions and limitations are discussed.

PMID- 18727100
TI  - Free-breathing cine MRI.
AB  - Standard MRI cine exams for the study of cardiac function are segmented over
      several heartbeats and thus require a breath-hold to minimize breathing motion
      artifacts, which is a current limitation of this approach. The purpose of this
      study was to develop a method for the measurement and correction of respiratory
      motion that is compatible with cine imaging. Real-time images were used to
      measure the respiratory motion of heart, to allow translations, rotations, and
      shears to be measured and corrected in the k-space domain prior to a final gated
      segmented reconstruction, using the same data for both purposes. A method for
      data rejection to address the effects of through-plane motion and complex
      deformations is described (respiratory gating). A radial k-space trajectory was
      used in this study to allow direct reconstruction of undersampled real-time
      images, although the techniques presented are applicable with Cartesian k-space
      trajectories. Corrected and uncorrected free-breathing gated-segmented images
      acquired over 18 sec were compared to the current standard breath-hold Cartesian
      images using both quantitative sharpness profiles (mm(-1)) and clinical scoring
      (1 to 5 scale, 3: clinically acceptable). Free-breathing, free-breathing
      corrected, and breath-hold images had average sharpness values of 0.23 +/- 0.04,
      0.38 +/- 0.04, and 0.44 +/- 0.04 mm(-1) measured at the blood-endocardium
      interface, and clinical scores of 2.2 +/- 0.5, 4.2 +/- 0.4, and 4.7 +/- 0.5,
      respectively.

PMID- 18727101
TI  - 3D high temporal and spatial resolution contrast-enhanced MR angiography of the
      whole brain.
AB  - Sensitivity encoding (SENSE) and partial Fourier techniques have been shown to
      reduce the acquisition time and provide high diagnostic quality images. However,
      for time-resolved acquisitions there is a need for both high temporal and spatial
      resolution. View sharing can be used to provide an increased frame rate but at
      the cost of acquiring spatial frequencies over a duration longer than a frame
      time. In this work we hypothesize that a CArtesian Projection Reconstruction-like
      (CAPR) technique in combination with 2D SENSE, partial Fourier, and view sharing
      can provide 1-2 mm isotropic resolution with sufficient temporal resolution to
      distinguish intracranial arterial and venous phases of contrast passage in whole
      brain angiography. In doing so, the parameter of "temporal footprint" is
      introduced as a descriptor for characterizing and comparing time-resolved view
      shared pulse sequences. It is further hypothesized that short temporal footprint
      sequences have higher temporal fidelity than similar sequences with longer
      temporal footprints. The tradeoff of temporal footprint and temporal acceleration
      is presented and characterized in numerical simulations. Results from 11 whole
      brain contrast-enhanced MR angiography studies with the new method with SENSE
      acceleration factors R = 4 and 5.3 are shown to provide images of comparable or
      higher diagnostic quality than the unaccelerated reference.

PMID- 18727103
TI  - Role of intraflagellar transport and primary cilia in skeletal development.
AB  - Primary cilia are nonmotile microtubule-based appendages extending from the
      surface of almost all vertebrate cells. The process of intraflagellar transport
      (IFT) is responsible for building and maintaining the structure and function of
      primary cilia. Disruption of Kif3a, a component of the Kinesin-II motor complex,
      disables anterograde IFT and leads to failure in the formation and maintenance of
      cilia. Likewise, the absence of IFT88/Tg737/Polaris, a core component of the IFT
      particle, results in the loss of cilia. Although primary cilia were described on
      chondrocytes almost 40 years ago, only recently has the functional significance
      of IFT and cilia in skeletal development been uncovered through the use of mouse
      models containing mutations or deletions in genes required to make and maintain
      cilia. Together, the results indicate that primary cilia/IFT are involved in
      coordinating multiple signaling pathways within the skeleton.

PMID- 18727104
TI  - Polyvalency: a promising strategy for drug design.
AB  - The simultaneous binding of multiple ligands on one entity to multiple receptors
      on another can result in an affinity that is significantly greater than that for
      the binding of a single ligand to a single receptor. This concept of
      "polyvalency" can be used to design molecules that are potent inhibitors of
      toxins and pathogens. We describe the design of potent polyvalent inhibitors that
      neutralize anthrax toxin in vivo as well as our attempts to elucidate the
      relationship between inhibitor structure and activity. We also highlight
      promising future avenues for research in polyvalent drug design.

PMID- 18727102
TI  - Inhibition of myogenesis by Notch: evidence for multiple pathways.
AB  - Notch signaling is critical for skeletal muscle development and regeneration,
      permitting the expansion of progenitor cells by preventing premature
      differentiation. We have interrogated the pathways through which ligand-mediated
      signaling inhibits myogenesis by identifying Notch target genes and assessing
      their impact on differentiation in vitro. Notch activation led to the robust
      induction of the transcriptional repressors Hey1 and HeyL in myoblasts, but only
      constitutive expression of Hey1 blocked myogenesis. siRNA-mediated knockdown of
      Hey1 had no effect on Notch's ability to inhibit differentiation, suggesting the
      existence of additional, possibly redundant pathways. We identified 82 genes
      whose expression was activated when C2C12 myoblasts were cultured in the presence
      of the Notch ligand Dll4. One of these, MyoR, is a novel Notch-responsive gene,
      whose protein product is known to repress myogenesis in vitro. siRNA-mediated
      knockdown of MyoR alone, or in combination with Hey1, was also ineffective at
      rescuing differentiation in the presence of Dll4. Our data support a model in
      which Notch signaling inhibits myogenesis through multiple pathways, two of which
      are defined by the Notch target genes Hey1 and MyoR.

PMID- 18727105
TI  - All-trans retinoic acid and intra-amniotic endotoxin-mediated effects on fetal
      sheep lung.
AB  - All-trans retinoic acid (RA) is a potent modulator of lung development.
      Chorioamnionitis, which is frequently associated with preterm birth, causes fetal
      lung inflammation and improves lung function but also results in alveolar
      simplification and microvascular injury. Endotoxin-mediated chorioamnionitis
      reduces RA concentration in the fetal lung to 16% of control values. We
      hypothesized that administration of RA to the fetus before induction of
      chorioamnionitis would preserve septation of the distal airspaces. Time-mated
      ewes with singletons were assigned to receive a fetal intramuscular treatment
      with 20,000 IU of RA in olive oil (or olive oil only) 3 hr prior to intra
      amniotic injection of endotoxin (20 mg, E. coli 055:B5) or saline, at 124-day
      gestational age and 7 days after the fetal treatment. The right cranial lung lobe
      was processed for morphometric analysis. RA treatment did not affect
      chorioamnionitis-induced fetal and systemic inflammation or interleukin-8
      concentrations in lung tissue. RA administration alone did not alter lung
      structure. Relative to control lungs (5 +/- 3 mL/kg), lung volume increased
      similarly with endotoxin (22 +/- 4 mL/kg) or RA plus endotoxin (20 +/- 3 mL/kg; P
      < 0.05). Alveolar wall thickness was 4.2 +/- 0.3 mum after endotoxin-induced
      chorioamnionitis, 6.0 +/- 0.4 mum in controls (P < 0.05 versus endotoxin) and 5.5
      +/- 0.2 mum after RA and endotoxin (P < 0.05 versus control, n.s. versus
      endotoxin). The ratio of airspace versus tissue was 4.6 +/- 0.3 in endotoxin
      induced chorioamnionitis, 2.1 +/- 0.3 in controls and 4.1 +/- 0.5 after RA and
      endotoxin. We conclude that fetal treatment with RA did not prevent inflammation
      induced alveolar simplification.

PMID- 18727106
TI  - Abnormal myocardial and coronary vasculature development in experimental hypoxia.
AB  - Oxygen availability is one of the necessary prerequisites for normal embryonic
      development. In our previous study we found that quail embryos incubated under
      hypoxic conditions (16% O(2)) die at embryonic day (ED) 9 with signs of heart
      failure. By ED4 and ED6 we found thinner ventricular wall and increased capillary
      density. We thus hypothesized that the cause of death would lie in severe
      myocardial and coronary maldevelopment. ED6 and 7 hypoxic hearts had thinner
      ventricular wall, especially left. There was a simultaneous increase in capillary
      density, most pronounced in the interventricular septum. This site corresponds to
      an area of tissue hypoxia and ensuing increased angiogenesis, and also formation
      of ventricular conduction system. Hypoxia had a positive effect on normal
      sequence of maturation of the conduction system evaluated by optical mapping at
      ED7. In sections from ED9 hypoxic hearts we found, in addition to thinner
      ventricular walls, irregularities in development of coronary tree (missing
      coronary ostia, absence of one coronary artery, and irregular arterial wall).
      This deficiency was due to decreased myocyte proliferation rather than to
      increased apoptosis. By Indian ink injection through the left ventricle we found
      in normoxic hearts regular coronary branching pattern, while in the hypoxic ones
      there was often only an irregular plexus. Embryonic hypoxia thus leads to
      increased capillarity and trabeculation to minimize diffusion distance. In the
      subsequent period there is a failure in organization of vascular plexus into
      normal vasculature, resulting in thin compact myocardium that likely leads to
      heart failure and embryonic death.

PMID- 18727107
TI  - Glucose transporter distribution in the vessels of the central nervous system of
      the axolotl Ambystoma mexicanum (Urodela: Ambystomatidae).
AB  - The GLUT-1 isoform of the glucose transporter is commonly considered a reliable
      molecular marker of blood-brain barrier endothelia in the neural vasculature
      organized in a three-dimensional network of single vessels. The central nervous
      system of the axolotl Ambystoma mexicanum is characterized by a vascular
      architecture that contains both single and paired vessels. The presence and
      distribution of the GLUT-1 transporter are studied in this urodele using both
      immunoperoxidase histochemistry and immunogold technique. Light microscopy
      reveals immunopositivity in both parenchymal and meningeal vessels. The
      transverse-sectioned pairs of vessels do not show the same size. Furthermore, in
      the same pair, the two elements often differ in diameter. The main regions of the
      central nervous system show a different percentage of the paired structures. Only
      immunogold cytochemistry reveals different staining intensity in the two adjoined
      elements of a vascular pair. Colloidal gold particles show an asymmetric
      distribution in the endothelia of both single and paired vessels. These particles
      are more numerous on the abluminal surface than on the luminal one. The particle
      density is calculated in both vascular types. The different values could indicate
      functional differences between single and paired vessels and between the two
      adjoined elements of a pair, regarding glucose transport.

PMID- 18727108
TI  - Lymphoid tissue ontogeny in the mummichog, Fundulus heteroclitus.
AB  - Most studies that examine the ontogeny of lymphoid organ development in
      teleostean fishes use species of interest to aquaculture or genetic research and,
      to date, have focused strictly on marine or freshwater species. The mummichog,
      Fundulus heteroclitus, also known as the estuarine killifish, is a unique model
      for studies on developmental immunobiology, because it is euryhaline, has a high
      degree of thermal tolerance, and has a unique reproductive strategy. Embryonic
      and larval mummichogs were examined for the ontogeny of lymphoid tissue
      development. The first lymphoid organ to appear was the head kidney at 1 dph,
      followed by the spleen at 1 wph, and then the thymus at 3 wph. Rag-1 was
      partially cloned and sequenced and shown to be highly conserved among other
      vertebrate Rag-1 genes. Using QT-PCR to monitor the temporal expression of Rag-1,
      it was shown to reach a maximum intensity at 3 and 4 wph and then to drop to pre
      2-wph levels. Overall, this study suggests that juvenile mummichogs do not
      possess the ability to mount T- or B-cell responses until some time after 5 wph.
      Even though the estuarine killifish tolerates a wide range of salinities, the
      developmental patterns of lymphoid tissues are similar to what has been reported
      for strictly marine (stenohaline) teleosts. Thus, the mummichog should be a
      convenient model for understanding the developmental immunobiology of most marine
      teleosts.

PMID- 18727109
TI  - Association between fibromyalgia and coronary heart disease and coronary
      catheterization.
AB  - BACKGROUND: Fibromyalgia (FM) has been associated with physical and emotional
      trauma including invasive medical procedures. Both FM and ischemic heart disease
      have been linked with depression. The purpose of this study was to
      retrospectively investigate the frequency of FM symptoms and physical findings
      among patients undergoing coronary catheterization. METHODS: Consecutive patients
      who underwent coronary angiography during the previous 6 mo were recruited.
      Patients with major depression, bi-polar disorder, schizophrenia, or malignancy
      were excluded. Patients underwent dolorimetry for tender-point assessment and
      completed the fibromyalgia impact questionnaire (FIQ). Group A included patients
      with significant coronary pathology (n = 43), group B included patients with
      normal coronary arteries (n = 50), and group C included patients with normal
      controls (n = 51). A cardiological score incorporated the number of coronary
      arteries with significant pathology and left ventricular function. Chi-square or
      Fisher's exact test was used for categorical data and a one-way analysis of
      variance for continuous variables; a multivariate linear regression was performed
      to compare groups. RESULTS: Significantly increased levels of tenderness were
      discovered among patients with coronary pathology compared with healthy controls.
      Significantly increased levels of depression were also found, as well as higher
      scores on the FIQ scale. On multivariate analysis, a positive correlation was
      demonstrated between tenderness/FIQ scores and a composite cardiological score.
      CONCLUSION: Coronary angiography is associated with a significantly increased
      frequency of pain, tenderness, and depression after 6 mo, apparent in both
      patients undergoing coronary procedures and patients with normal coronaries. This
      association may impact the outcome of patients with significant coronary disease.

PMID- 18727110
TI  - Carbon-coated stents in patients with acute coronary syndromes.
AB  - BACKGROUND: For patients with ST elevation myocardial infarction (STEMI) or non
      ST elevation myocardial infarction (NSTEMI), rapid restoration of coronary blood
      flow is the primary therapeutic goal. Because of the acute nature of this
      clinical presentation, bleeding risks may not be adequately evaluated, limiting
      the use of drug-eluting stents, since premature discontinuation of antiplatelet
      therapy strongly predicts stent thrombosis. We evaluated angiographic and
      clinical results of non-drug-eluting carbon-coated stents. METHODS: In this
      prospective observational study, angiographic and clinical 6-mo results of a
      carbon-coated stent for treatment of acute lesions in native coronary arteries
      were evaluated. Angiographic main outcome measures included in-stent late loss
      and binary restenosis rate. Major adverse cardiac events (MACEs) were defined as
      any death, Q-wave myocardial infarction (MI), and target lesion
      revascularization. RESULTS: We included 320 patients with STEMI (n = 205) or
      NSTEMI (n = 115) with 360 lesions. Reference vessel diameter was 2.93 +/- 0.53 mm
      and stented length 22.7 +/- 13.8 mm. Angiographic follow-up was available in 220
      of 360 lesions (61%). In-stent late loss was 0.69 +/- 0.75 mm, with a binary
      restenosis rate of 19.1%. For the total segment late loss was 0.74 +/- 0.77 mm
      and binary restenosis rate 21.4%. Clinical follow-up for 97.4% of discharged
      patients was available. Hierarchical MACEs were death in 14 patients (4.4%), Q
      wave MI in 3 patients (0.9%), and target lesion revascularization in 39 patients
      (12.2%). CONCLUSION: In this prospective, observational study, the use of a
      carbon-coated stent for treatment of lesions in patients with STEMI or NSTEMI was
      associated with a low late loss, translating into a low binary angiographic
      restenosis rate within a 6-mo follow-up.

PMID- 18727111
TI  - Assessment of regional systolic and diastolic functions affected by atorvastatin
      in coronary artery disease using tissue Doppler imaging.
AB  - BACKGROUND: Several studies have shown regional left ventricular (LV) systolic
      and diastolic changes associated with coronary artery disease (CAD). Statins may
      have beneficial pleiotropic effects in addition to their lipid-lowering
      properties. HYPOTHESIS: We hypothesized that atorvastatin can improve regional LV
      systolic and diastolic functions in CAD patients using tissue Doppler imaging
      (TDI). METHODS: A total of 63 patients with hyperlipemia and CAD were studied.
      Forty-three patients were given 10 mg daily of atorvastatin and 20 patients were
      assigned only a low-fat diet. Tissue Doppler imaging was applied to evaluate LV
      peak systolic velocity (VS), early diastolic velocity (VE), and late diastolic
      velocity (VA) in 18 segments. The mean value of LV peak systolic velocity
      (VS(')), the mean value of early diastolic velocity (VE(')), and the mean value
      of late diastolic velocity (VA(')), in 18 segments were calculated. RESULTS:
      Compared with the baseline, VS('), and VE('), increased significantly after the
      therapy in the atorvastatin group (p < 0.05), while there was no change in the
      control group (p > 0.05). At 6 mo of therapy, a significant reduction in total
      cholesterol, triglyceride, and low-density lipoprotein (LDL) cholesterol was
      observed in the 2 groups (p < 0.05). CONCLUSIONS: These findings demonstrate that
      atorvastatin can improve regional LV systolic and diastolic functions in CAD
      patients independent of its lipid-lowering properties.

PMID- 18727112
TI  - Chromaffin cells in the amphibian urodele Triturus carnifex show ultrastructural
      features indicative of a vesicle-mediated mode of cell degranulation.
AB  - Recently, suggestive evidence for piecemeal degranulation (PMD), a particulate
      pattern of cell secretion accomplished by vesicle-mediated extracellular
      transport of granule-stored material, has been provided by electron microscopy
      investigations in chromaffin cells of different vertebrate species. In this
      study, chromaffin tissue from the interrenal gland of the amphibian urodede
      Triturus carnifex has been investigated by quantitative transmission electron
      microscopy in search for ultrastructural clues indicative of a vesicle-mediated
      mode of cell degranulation. Interestingly, a single type of chromaffin cell is
      recognizable in T. carnifex, which undergoes seasonal variations in its
      adrenaline and noradrenaline granule ratio according to an annual cycle that
      matches the trend of changes in secondary sexual characters. In this study, we
      looked for a series of ultrastructural changes regarded as highly specific for
      PMD. We calculated the percentage of (i) resting, unaltered granules (type 1
      granules); (ii) granules with changes indicative of progressive release of
      secretory materials, that is, granules with lucent areas in their cores, reduced
      electron density, disassembled matrices, and residual cores (type 2 granules);
      and (iii) membrane empty containers (type 3 granules) in chromaffin cells of T.
      carnifex during the annual cycle. We found a significant increase in type 2 and 3
      granules, accompanied by a significant decrease in type 1 granules, in the April
      and November samples. During the same seasonal periods, the number per net
      cytoplasmic area of 30-100-nm diameter electron-dense vesicles was found to be
      significantly augmented, and there was also an augmented percentage of chromaffin
      granules showing blebs or protrusions in their profiles. These ultrastructural
      data are indicative of an increased vesicle-mediated transport of chromaffin
      granule products for extracellular release in the amphibian T. carnifex in
      accordance with the increased rate of catecholamine release. This vesicle
      mediated pattern of cell secretion suits the schema of PMD. In an evolutionary
      perspective, these findings suggest that PMD is a secretory pathway that has been
      highly conserved throughout vertebrate classes. Anat Rec, 2009. (c) 2008 Wiley
      Liss, Inc.

PMID- 18727113
TI  - Detailed process of bone remodeling after achievement of osseointegration in a
      rat implantation model.
AB  - Osseointegration is regarded as the most appropriate implant-bone interface in
      dental implantation. However, damaged bone with empty osteocytic lacunae driven
      by implant cavity preparation remains even after the completion of
      osseointegration. Although previous studies have suggested the occurrence of bone
      remodeling around implants, information on its detailed process is meager. Our
      study aimed to examine the fate of bone around titanium implants after the
      establishment of osseointegration on an animal model using the rat maxilla.
      Titanium implants were inserted into prepared bone cavities of the rat maxilla.
      Bone formation and maturation processes were evaluated by double staining for
      alkaline phosphatase and tartrate-resistant acid phosphatase,
      immunohistochemistry for bone matrix proteins, vital staining with calcein, and
      elemental mapping with an electron probe microanalyzer. Bone with empty
      osteocytic lacunae or pyknosis remained between the intact preexisting and newly
      formed woven bones at post 1 month. It gradually decreased to disappear
      completely by active bone remodeling with a synchronized coordination of alkaline
      phosphatase-positive osteoblasts and tartrate-resistant acid phosphatase-reactive
      osteoclasts at post 3 months, thickening to be replaced by compact bone. Dynamic
      labeling showed two clear lines in the newly formed bone around the implant
      through this experimental period. Electron probe microanalyzer analysis
      demonstrated chronologically increased levels of Ca and P in the newly formed
      bone identical to those in the surrounding bone at post 2.5 months. These
      findings indicate that continuous bone remodeling after the achievement of
      osseointegration causes replacement of the damaged bone by compact bone as well
      as an improvement in bone quality. Anat Rec, 2009. (c) 2008 Wiley-Liss, Inc.

PMID- 18727114
TI  - Three-dimensional reconstruction of the optic canal-based on multislice helical
      CT: a comparison analysis with skull dissection of 40 postmortem cases.
AB  - Decompression operation of the optic canal via the nasal path under endoscope is
      widely used, but it is both a challenging and controversial method.
      Unsatisfactory results were largely associated with otolaryngologists' limited
      understanding of the real anatomical situations of the optic canal before
      operation. To provide otolaryngologists with the real situations and data
      preoperation, multislice helical CT was used to reconstruct the images of the
      optic canal. Using multislice helical CT-aided three-dimensional reconstructive
      methods in combination with direct anatomic measurement, we dissected and
      analyzed the shape of the optic canal and its anatomic relationship with the
      adjoining structures in 40 intact postmortem skull samples. The In-Space
      technique clearly showed the structure and the related region of the optic canal.
      The virtual endoscopy technique showed superbly the spatial appearance and
      topography of the inner optic canal and also gave the inner structure of the
      optic canal optically. There was no statistic difference in three-dimensional
      reconstructive data with that obtained by anatomical measurements and thus can be
      used to directly instruct the clinic operation. These results demonstrate that a
      combined In-Space technique with virtual endoscopy can accurately define the
      subtle structure and the related region of the optical canal. In conclusion,
      multislice helical CT-based three-dimensional reconstruction is of important
      value for clinical operations.

PMID- 18727115
TI  - Initial results of primary device closure of large muscular ventricular septal
      defects in early infancy using perventricular access.
AB  - OBJECTIVES: To report our experience with the use of the Amplatzer muscular
      ventricular septal defect (VSD) occluder, using direct right ventricle free wall
      puncture for primary closure of muscular VSDs in infants. BACKGROUND: Young
      infants with heart failure due to large or multiple muscular VSDs often require
      intervention at a stage when percutaneous device closure is impractical due to
      delivery system limitations. There are considerable benefits to avoiding bypass
      in these infants. METHODS: Patients with suitable muscular VSDs, considered too
      small for transvenous closure, underwent periventricular muscular VSD closure
      under transesophageal echo (TEE) guidance. RESULTS: Eight infants underwent the
      procedure. The median age was 14 weeks (2-41) with median weight of 4 kg (3-6.6).
      Four patients had additional VSDs and one patient had previous repair of
      coarctation. One patient had dextrocardia and severe left ventricular impairment
      due to an associated cardiomyopathy. The median VSD size was 8 mm (range, 4-10
      mm). A single device (6-12 mm) was deployed in each patient, the size chosen
      being 1-2 mm larger than the TEE measurement. Two patients had subsequent
      pulmonary artery banding, with absorbable bands, because of moderate residual
      shunting through additional VSDs. The latest echo study at a median of 7.2 weeks
      (0.5-66) post device implantation revealed no patients with a hemodynamically
      significant shunt. CONCLUSION: Perventricular muscular VSD closure can be safely
      and effectively undertaken in small infants with suitable muscular defects, and
      this strategy can avoid the need for bypass.

PMID- 18727116
TI  - The successful use of alternative routes of vascular access for performing
      pediatric interventional cardiac catheterization.
AB  - OBJECTIVE: The objective of this study is to examine the safety/efficacy of
      alternative routes of vascular access (ARVA) for successful performance of
      interventions. BACKGROUND: Complex interventional catheterizations may be
      required in children with limited vascular access, vascular constraints relative
      to size, and hemodynamic instability. Our approach has been to utilize ARVA in
      selected cases. METHODS: ARVA pertains to any vessel excluding femoral,
      jugular/subclavian veins, or umbilical access. A retrospective review performed
      on patients with an intervention utilizing ARVA between August 1995 and January
      2004 was performed. Patients were divided by clinical status: critically
      ill/emergent (A), elective cases (B). Procedural success was based on previously
      published criteria. RESULTS: Sixty-four interventions were performed in 50
      patients using 54 ARVA. ARVA utilized: radial (1), axillary (2), brachial (2),
      carotid arteries (25); brachial (2) hepatic (9) veins; and open chest/direct
      cardiac puncture (13). ARVA provided successful access to target lesions.
      Interventions included stents (30), valvuloplasty (16), angioplasty (14), and one
      each of vascular occlusion, septal occlusion, accessory pathway ablation, and
      septostomy. Group A patients were smaller (P < 0.0002) and younger (P < 0.004)
      than B. All open chest/direct cardiac and the majority (71%) of carotid arterial
      approaches were performed in group A. Fifty-six (88%) inteventions were
      successful with no difference between groups A (88%) and B (86%). There were two
      complications. Neither resulted in long-term sequelae. CONCLUSIONS: ARVA may
      provide a strategic advantage that may be safely applied to a variety of
      interventions regardless of patient size or degree of illness. These techniques
      may further extend the scope of successful interventions in children.

PMID- 18727117
TI  - A unique complication of the retrograde approach in angioplasty for chronic total
      occlusion of the coronary artery.
AB  - The retrograde approach for chronic total occlusion of coronary arteries is a new
      treatment strategy, although its attendant complications have not yet been fully
      appreciated. We report a case of isolated left ventricular cardiac tamponade
      caused by guidewire-induced perforation of the septal branch during the
      retrograde approach, which was subsequently diagnosed by computed tomography (CT)
      and which required surgical drainage. Guidewire-induced perforation of the septal
      branch was successfully treated by autologous subcutaneous tissue embolization of
      the perforated coronary artery. This is the first case of its kind to date.

PMID- 18727118
TI  - Treatment of chronic total occlusion by retrograde passage of stents through an
      epicardial collateral vessel.
AB  - Chronic total occlusion (CTO) may occur in as many as 30-40% of patients with
      coronary artery disease. Retrograde revascularization through a collateral
      channel has been described earlier. We report the first case of retrograde
      passage of a stent through an epicardial collateral to revascularize a right
      coronary artery CTO.

PMID- 18727119
TI  - Clinical inference: critically weighing the evidence from trials and registries
      to make clinical decisions.
AB  - The results of even excellent randomized trials are applicable primarily to
      patients who would have met all of the inclusion criteria and none of the
      exclusion criteria, specified in the study protocol (generalizability or external
      validity). In addition, three important sources of potential systematic error, or
      bias, are as follows: selection bias, confounding, and information bias.
      Selection bias is relevant to nearly all randomized clinical trials in terms of
      external validity, or generalizability, of even internally valid results.
      Selection bias, confounding, and information bias can all limit the internal
      validity of prospective, registry data. Carefully reading the methods sections of
      both randomized trial and registry reports, with these potential limitations in
      mind, is the first step in critically using clinical research to help make more
      informed clinical decisions.

PMID- 18727120
TI  - Serial late dilatations of expanded polytetrafluoroethylene-covered stents in
      porcine aorta.
AB  - BACKGROUND: Covered stents may be desirable for stenting of coarctations.
      OBJECTIVES: To evaluate the ability of Atrium expanded polytetrafluoroethylene
      (ePTFE)-covered stents to be implanted and then serially dilated to the size of
      the adjacent aorta during a rapid growth period in swine. METHODS: Eight
      Yorkshire pigs (7 females) with a mean weight of 18.3 +/- 0.7 kg had an Atrium
      ePTFE-covered stent deployed in the descending aorta. Five of these animals also
      had an identical Atrium bare metal stent (BMS) control deployed in the descending
      aorta. All swines were recatheterized with the first dilatation of the stents to
      14 mm at day 100. Four of these animals were recatheterized at day 145 and
      euthanized, and the remaining four swine were recatheterized with a second
      dilatation to 18-20 mm, 195 days after initial implantation. RESULTS: All stents
      were deployed without device malfunction, and both uncovered and covered stents
      were successfully dilated from 10 to 11 mm to the size of the adjacent aorta (16
      20 mm). There was no gradient across either type of stent on recatheterization
      and all stents were well sized to the native aorta. Only the size of the aorta
      limited the degree of stent dilatation. The Atrium covered stents consistently
      recoiled after maximal dilatation and required higher pressures for further
      expansion. Gross damage to the aorta was noted in two animals in which stents
      were dilated to >20% the diameter of the native aorta. In stent neointimal
      thickness was equivalent for both types of stent. CONCLUSIONS: Atrium ePTFE
      covered stents can be implanted at 10-11 mm and serially dilated to accommodate
      for rapid aortic growth. High pressure balloons are required for dilatation of
      ePTFE-covered stents. Atrium covered stents exhibited more recoil and
      foreshortening at larger diameters.

PMID- 18727121
TI  - Percutaneous closure of a complex posttraumatic muscular ventricular septal
      defect.
AB  - We report the percutaneous closure of a complex traumatic ventricular septal
      defect resulting from a stab wound to the anterior chest. The patient presented
      with heart failure 3 months after the initial trauma. Evaluation revealed a new
      large ventricular septal defect with diminished cardiac function. Closure was
      accomplished with a combination of an Amplatzer muscular ventricular septal
      defect occluder and two Amplatzer vascular plugs.

PMID- 18727122
TI  - Amplatzer vascular plug closure of a Blalock-Taussig shunt through a Glenn shunt.
AB  - We describe an unusual route and uncommon device use for the percutaneous closure
      of a modified Blalock-Taussig (BT) shunt. A 4-year-old male had presented with
      severe upper body swelling after a bidirectional Glenn shunt done one month
      earlier. The BT shunt which was clipped during the surgery was found to be
      patent. The BT shunt was finally closed from the bidirectional Glenn using an
      Amplatzer vascular plug, resulting in symptom relief.

PMID- 18727123
TI  - Staged percutaneous atrial septal defect closure and pulmonic balloon
      valvuloplasty in an adult with congenital heart disease.
AB  - Combined atrial septal defect and pulmonic stenosis, while a common occurrence in
      children, is relatively uncommon in adults. There is no widely accepted order in
      which the defects should be corrected. We report a case that highlights the
      hemodynamics and the technical dilemma of deciding which lesion to correct first.

PMID- 18727124
TI  - Time is muscle; but should it be D2B or D2T?

PMID- 18727125
TI  - One year perspective on COURAGE.
AB  - Doctor: "Ma'am you need an angioplasty". PATIENT: "Doctor, the newspaper says
      that medicine is as good as angioplasty". Doctor: "Ma'am you're having a heart
      attack". The COURAGE trial was published 1 year ago and received attention from
      the media, patients, and other medical specialties concerning the value of
      percutaneous coronary intervention. Now, 1 year later there has been time to
      reflect on COURAGE, and some newer data have emerged. The purpose of this article
      is to put into perspective the issues surrounding the COURAGE trial and suggest
      different approaches for future trials of stable coronary artery disease.

PMID- 18727126
TI  - Atraumatic complex transradial intervention using large bore sheathless guide
      catheter.
AB  - The Asahi sheathless guide catheter system is a hydrophilic catheter with a
      central dilator that does not require an introducer sheath during transradial
      percutaneous coronary intervention. Conventional sheath introducers are often 1-
      to 2F larger than the catheter itself; therefore, this system enables the use of
      a larger French catheter during procedures than would otherwise be possible using
      conventional techniques. We describe the use of a 7.5F sheathless guide catheter
      system with a smaller outer diameter than a conventional 6F introducer sheath in
      16 cases performed transradially involving rotablation, crush stent bifurcation
      lesions, 7F proximal protection, and thrombectomy devices. Such cases would
      otherwise not always be possible if performed using conventional transradial
      techniques in patients with smaller radial artery sizes.

PMID- 18727127
TI  - Weak partitioning chromatography for anion exchange purification of monoclonal
      antibodies.
AB  - Weak partitioning chromatography (WPC) is an isocratic chromatographic protein
      separation method performed under mobile phase conditions where a significant
      amount of the product protein binds to the resin, well in excess of typical
      flowthrough operations. The more stringent load and wash conditions lead to
      improved removal of more tightly binding impurities, although at the cost of a
      reduction in step yield. The step yield can be restored by extending the column
      load and incorporating a short wash at the end of the load stage. The use of WPC
      with anion exchange resins enables a two-column cGMP purification platform to be
      used for many different mAbs. The operating window for WPC can be easily
      established using high throughput batch-binding screens. Under conditions that
      favor very strong product binding, competitive effects from product binding can
      give rise to a reduction in column loading capacity. Robust performance of WPC
      anion exchange chromatography has been demonstrated in multiple cGMP mAb
      purification processes. Excellent clearance of host cell proteins, leached
      Protein A, DNA, high molecular weight species, and model virus has been achieved.

PMID- 18727128
TI  - Enhancement of transient gene expression and culture viability using Chinese
      hamster ovary cells overexpressing Bcl-x(L).
AB  - Transient gene expression (TGE) provides a method for quickly delivering protein
      for research using mammalian cells. While high levels of recombinant proteins
      have been produced in TGE experiments in HEK 293 cells, TGE efforts in the
      commercially prominent CHO cell line still suffer from inadequate protein yields.
      Here, we describe a cell-engineering strategy to improve transient production of
      proteins using CHO cells. CHO-DG44 cells were engineered to overexpress the anti
      apoptotic protein Bcl-x(L) and transiently transfected using polyethylenimine
      (PEI) in serum-free media. Pools and cell lines stably expressing Bcl-x(L) showed
      enhanced viable cell density and increased production of a glycosylated,
      therapeutic fusion protein in shake flask TGE studies. The improved cell lines
      showed fusion protein production levels ranging from 12.6 to 27.0 mg/L in the
      supernatant compared to the control cultures which produced 6.3-7.3 mg/L,
      representing a 70-270% increase in yield after 14 days of fed-batch culture. All
      Bcl-xL-expressing cell lines also exhibited an increase in specific productivity
      during the first 8 days of culture. In addition to increased production, Bcl-x(L)
      cell lines maintained viabilities above 90% and less apoptosis compared to the
      DG44 host which had viabilities below 60% after 14 days. Product quality was
      comparable between a Bcl-xL-engineered cell line and the CHO host. The work
      presented here provides the foundation for using anti-apoptosis engineered CHO
      cell lines for increased production of therapeutic proteins in TGE applications.

PMID- 18727129
TI  - Proteome-based identification of fusion partner for high-level extracellular
      production of recombinant proteins in Escherichia coli.
AB  - Extracellular production of recombinant proteins in Escherichia coli has several
      advantages over cytoplasmic or periplasmic production. However, nonpathogenic
      laboratory strains of E. coli generally excrete only trace amounts of proteins
      into the culture medium under normal growth conditions. Here we report a
      systematic proteome-based approach for developing a system for high-level
      extracellular production of recombinant proteins in E. coli. First, we analyzed
      the extracellular proteome of an E. coli B strain, BL21(DE3), to identify
      naturally excreted proteins, assuming that these proteins may serve as potential
      fusion partners for the production of recombinant proteins in the medium. Next,
      overexpression and excretion studies were performed for the 20 selected fusion
      partners with molecular weights below 40 kDa. Twelve of them were found to allow
      fused proteins to excrete into the medium at considerable levels. The most
      efficient excreting fusion partner, OsmY, was used as a carrier protein to
      excrete heterologous proteins into the medium. E. coli alkaline phosphatase,
      Bacillus subtilis alpha-amylase, and human leptin used as model proteins could
      all be excreted into the medium at concentrations ranging from 5 to 64 mg/L
      during the flask cultivation. When only the signal peptide or the mature part of
      OsmY was used as a fusion partner, no such excretion was observed; this confirmed
      that these proteins were truly excreted rather than released by outer membrane
      leakage. The recombinant protein of interest could be recovered by cleaving off
      the fusion partner by enterokinase as demonstrated for alkaline phosphatase as an
      example. High cell density cultivation allowed production of these proteins to
      the levels of 250-700 mg/L in the culture medium, suggesting the good potential
      of this approach for the excretory production of recombinant proteins.

PMID- 18727130
TI  - Non-invasive mass transfer measurements in complex biofilm-coated structures.
AB  - We demonstrate a novel application of (13)C pulsed field gradient (PFG) NMR to
      monitor mass transfer, due to both flow and diffusion, in a 3D complex porous
      support structure modified by biofilm growth. This enables timescales an order of
      magnitude larger than previously possible to be accessed with respect to
      displacement probability distribution (propagator) measurements. The evolution in
      the propagator shape with observation time to the Gaussian asymptote (constant
      dispersion coefficient) is consequently well resolved. We also simulated the
      measured displacement propagators with good agreement between experiment and
      prediction. The methodology has significant potential for the selective
      characterization of the transport of nutrients, metabolic products, pollutants
      and biocides in such complex biofilm-containing structures.

PMID- 18727131
TI  - Formulation, characterization, and in vitro evaluation of quantum dots loaded in
      poly(lactide)-vitamin E TPGS nanoparticles for cellular and molecular imaging.
AB  - We developed a novel system of poly(lactide acid)-d-alpha-tocopheryl polyethylene
      glycol 1000 succinate (PLA-TPGS) nanoparticles (NPs) for quantum dots (QDs)
      formulation to improve imaging effects and reduce side effects as well as to
      promote a sustainable imaging. The QDs-loaded PLA-TPGS NPs were prepared by a
      modified solvent extraction/evaporation method, which were then characterized by
      laser light scattering (LLS) for size and size distribution; field emission
      scanning electron microscopy (FESEM), atomic force microscopy (AFM) and
      transmission electron microscope (TEM) for surface morphology. Surface chemistry
      of the QDs-loaded PLA-TPGS NPs was analyzed by X-ray photoelectron microscopy
      (XPS) and Fourier transform infra-red spectroscopy (FTIR). Encapsulation
      efficiency of the QDs in the polymeric nanoparticles was measured by inductively
      coupled plasma optical emission spectrometry (ICP-OES). The photostability of the
      QDs formulated in the PLA-TPGS nanoparticles was investigated as changes in the
      florescence intensity versus the irradiation time. Confocal laser scanning
      microscopy (CLSM) was used to image the cellular uptake of the QDs-loaded NPs by
      MCF-7 cells. Methylthiazolyldiphenyl-tetrazolium (MTT) assay was employed to
      assess the viability of MCF-7 cells incubated with the QDs formulated by the PLA
      TPGS NPs versus the mercaptoacetic acid (MAA)-coated QDs. It was found that the
      QDs formulated in the PLA-TPGS NPs can result in higher fluorescence intensity
      and higher photostability than the bare QDs as well as lower cytotoxicity than
      the MAA-coated QDs.

PMID- 18727132
TI  - What do we know about quality of life in dementia? A review of the emerging
      evidence on the predictive and explanatory value of disease specific measures of
      health related quality of life in people with dementia.
AB  - OBJECTIVE: Given its complexity, there is growing consensus on the need to
      measure patient-rated broad outcomes like health-related quality of life (HRQL)
      as well as discrete functions like cognition and behaviour in dementia. This
      review brings together current data on the distribution, determinants and course
      of HRQL in dementia to investigate the predictive and explanatory value of
      measures of HRQL in people with dementia. DESIGN: A systematic review of papers
      in English published up to October 2007 to identify data on the use of disease
      specific measures of HRQL in dementia. RESULTS: There are no clear or consistent
      associations between socio-demographic variables and HRQL. There is no convincing
      evidence that lower cognition or greater activity limitation is associated with
      lower HRQL. There is a strong suggestion that depression is consistently
      associated with decreased HRQL in dementia. However, the magnitude of the
      associations observed is moderate only and the proportion of variance explained
      is low suggesting that depression and HRQL are different constructs. We currently
      know almost nothing about the natural history of HRQL in dementia or what
      attributes or interventions promote or inhibit HRQL life for people with
      dementia. CONCLUSIONS: While in other illnesses there may be simple association
      between HRQL and an easily measurable clinical variable, in dementia this is not
      so. There are now instruments available with which to measure disease-specific
      HRQL directly in clinical trials and other studies that can yield informative
      data.

PMID- 18727134
TI  - Factors associated with non-use of antipsychotics among older residents with
      schizophrenia in long-term institutional care.
AB  - OBJECTIVE: To investigate factors associated with non-use of antipsychotics among
      older schizophrenia residents in long-term institutional care. DESIGN: A
      retrospective study was designed using cross-sectional data gathered between 1
      January and 30 June 2006 in Finland. Data were extracted from the Resident
      Assessment Instrument (RAI) database, based on Minimum Data Set for long-term
      care facilities (MDS-LC) assessments. PARTICIPANTS: Residents with schizophrenia
      65 years or older were included, giving a total of 356 patient assessments.
      RESULTS: The prevalence of older schizophrenia residents not receiving any
      antipsychotic medication was 18.5%. Factors independently associated with non-use
      of antipsychotics in the logistic regression model were: severe degree of
      functional impairment, severely impaired vision, any diagnosis of dementia and
      severe underweight. There was a negative association between non-use of
      antipsychotics and a factor 'had arrived from a psychiatric hospital'.
      CONCLUSIONS: Severe degree of functional impairment and dementia were the main
      findings associated with non-use of antipsychotics in this resident group.

PMID- 18727133
TI  - Integrated specialty mental health care among older minorities improves access
      but not outcomes: results of the PRISMe study.
AB  - OBJECTIVE: In this secondary data analysis of Primary Care Research in Substance
      Abuse and Mental Health for the Elderly (PRIMSe) study, we hypothesized that
      older minorities who receive mental health services integrated in primary care
      settings would have greater service use and better mental health outcomes than
      older minorities referred to community services. METHOD: We identified 2,022 (48%
      minorities) primary care patients 65 years and older, who met study inclusion
      criteria and had either alcohol misuse, depression, and/or anxiety. They were
      randomized to receive treatment for these disorders in the primary care clinic or
      to a brokerage case management model that linked patients to community-based
      services. Service use and clinical outcomes were collected at baseline, three
      months and six months post randomization on all participants. RESULTS: Access to
      and participation in mental health /substance abuse services was greater in the
      integrated model than in referral; there were no treatment by ethnicity effects.
      There were no treatment effects for any of the clinical outcomes; Whites and
      older minorities in both integrated and referral groups failed to show clinically
      significant improvement in symptoms and physical functioning at 6 months.
      CONCLUSIONS: While providing services in primary care results in better access to
      and use of these services, accessing these services is not enough for assuring
      adequate clinical outcomes.

PMID- 18727135
TI  - Effects of directed gel degradation and collagenase digestion on the integration
      of neocartilage produced by chondrocytes encapsulated in hydrogel carriers.
AB  - Chondrocytes were encapsulated in non-degrading and partially degrading
      poly(ethylene glycol) (PEG) gels in apposition to native cartilage layers in
      order to examine the effects of gel degradation on the integration of regenerated
      cartilaginous matrix with native tissue. In addition, the effect of collagenase
      predigestion of the native cartilage surfaces on this integration was examined in
      studies with partially degrading co-polymer gels. Integration was quantitatively
      assessed by mechanical measurements of adhesive strength, and visualized by
      histological staining and non-destructive ultrasound analysis. Constructs with
      encapsulated chondrocytes and a non-degrading gel layer had significantly higher
      adhesive strength than partially degrading gel constructs and non-degrading gel
      constructs without cells. In addition, better maintenance of proper cell
      morphology was observed near the gel-cartilage interface in non-degrading gel
      constructs than in partially degrading gel constructs after 8 weeks of in vitro
      culture. Facile collagen distribution in the degrading gels appeared to have a
      significant effect on mechanical adhesion measurements only when the native
      cartilage surface was predigested with collagenase. Ultrasound analysis provided
      qualitative evidence of cartilaginous matrix evolution and non-destructive
      imaging of developing constructs and the interface between newly formed matrix
      and existing cartilage tissue.

PMID- 18727136
TI  - Are micropatterned substrates for directed cell organization an effective method
      to create ordered 3D tissue constructs?
AB  - Tissue-engineered constructs grown in vitro tend to have random arrangements of
      cells and extracellular matrix (ECM) and much research effort is aimed at
      developing long-range organization in tissue-engineered constructs. Contact
      guidance, which utilizes substrates with topographical patterns of the scale of
      single cells (0.1-100 microm) to limit cell adhesion to specific locations and to
      influence cell shape and orientation, is one popular method which has been used
      to generate order in cell cultures. The use of contact guidance to generate three
      dimensional (3D) order relies on the assumption that a newly forming cell or
      tissue layer will be guided by the organization of the previous layer, which has
      been organized by the patterned substrate. However, the ability for cellular
      patterns to be coupled through organized cell layers from a patterned substrate
      has not been effectively demonstrated. The results of this study demonstrate
      that, although the patterned substrate induces initial organization and
      polarization, this organization is not sustained in the successive cell/tissue
      layers that form above the initial cell layer. This finding suggests that cells
      must be in direct contact with the patterned substrate to maintain their
      polarization, orientation and positional organization. Therefore, contact
      guidance does not appear to be a promising technique to create ordered 3D tissue
      engineered constructs. Alternative techniques, in particular those involving the
      application of mechanical, electrical or flow fields, may be more useful in
      sustaining organization in multilayered constructs as the organizational
      influence extends as a field into 3D space.

PMID- 18727138
TI  - Robotic-assisted radical cystectomy.
AB  - OBJECTIVE: To evaluate the emerging role of robotic-assisted radical cystectomy
      (RARC) in the management of bladder cancer. METHODS: Review of the published
      literature on robotic-assisted radical cystectomy, including data from our
      cystectomy series of 30 patients. RESULTS: Nearly 150 procedures have been
      performed worldwide. The benefits of robotic-assisted operations are similar to
      those of laparoscopically-performed procedures. RARC appears to be technically
      safe, oncologically and functionally equivalent to open (ORC) and laparoscopic
      radical cystectomy (LRC). However, RARC offers superior ergonomics and better
      vision. These benefits come at extra initial capital expenditure and subsequent
      higher maintenance costs. CONCLUSION: With the rapid spread of robotics, it is
      likely that RARC will become the standard of care in units with access to the
      technology.

PMID- 18727137
TI  - Role of NADPH oxidase in tissue growth in a tissue engineering chamber in rats.
AB  - Previously we described a subcutaneous arteriovenous loop (AVL)-based tissue
      engineering chamber system, which contains an intrinsic circulation circuit
      created by joining the proximal ends of the femoral artery and vein with a venous
      graft. We showed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      was involved in mediating neovascularization inside the chamber. However, the
      role of NADPH oxidase in tissue formation in the chamber is unknown. In this
      study, we examined the effects of gp91ds-tat, a peptidyl inhibitor of NADPH
      oxidase, on the growth of engineered tissue blocks, using a rat chamber model.
      Chambers containing the AVL were filled with Matrigel mixed with gp91ds-tat (100
      microM) or the scrambled control peptide. At 14 days, in control chambers, most
      of the Matrigel was replaced by granulation tissues; gp91ds-tat treatment
      significantly reduced the level of reactive oxygen species and retarded the
      tissue formation process. Although the total number of blood vessels per unit
      cellularized area was not different between two groups, most vessels in gp91ds
      tat-treated tissues had smaller lumens as compared to control. The total area
      occupied by vessel lumens was much less in gp91ds-tat-treated tissues (10.3 +/-
      1.3% in control vs. 1.7 +/- 0.5% in gp91ds-tat group; p < 0.001). In vitro,
      gp91ds-tat treatment reduced proliferation and migration of cultured
      microvascular endothelial cells. Our data suggest that inhibition of NADPH
      oxidase function retards tissue formation in the tissue engineering chamber,
      which may be related to the malformed new blood vessels in the engineered tissue.

PMID- 18727139
TI  - Single session educational programme for caregivers of psychogeriatric in
      patients--results from a randomised controlled pilot study.
AB  - BACKGROUND: Family caregivers of patients with psychiatric or medical disorders
      are at risk of developing psychological distress. Studies including family
      caregivers of patients with dementia have shown that psychoeducative programmes
      reduce distress and postpone institutionalisation. Little is known about the
      effect of psychoeducation of relatives of psychogeriatric patients. The aim of
      this study was to investigate the effect of a single-session educational
      intervention of relatives of psychogeriatric in-patients. METHODS: A randomised
      controlled intervention study was carried out with 16 relatives in the
      intervention group and 14 in the control group. The intervention was carried out
      as a single session programme. Primary outcome measures were psychological well
      being and depression as measured by means of General Health Questionnaire (GHQ
      30), Impact of Event Scale (IES) and Geriatric Depression Scale (GDS). Outcome
      measures were performed at baseline, at discharge and at 3-month follow-up.
      RESULTS: Psychological distress was high. Daughters were more depressed and
      distressed than spouses. Patients' diagnoses did not seem to exert influence on
      the relatives' well-being. There was a significant worsening of psychological
      distress in the intervention group as measured by GHQ-30. CONCLUSIONS: The study
      is small and results must be interpreted with caution. Distress among relatives
      was high regardless of patient's diagnosis. The results of the intervention might
      lead us to conclude that single-session interventions towards this specific group
      of relatives do not improve psychological stress and might, in some aspects, even
      worsen it.

PMID- 18727140
TI  - A valid instrument for measuring informal care time for people with dementia.
AB  - OBJECTIVE: An economic evaluation of dementia-related interventions from a
      societal perspective should take account of informal caregiving. We assessed
      informal caregiving time and report our findings on the validity and stability of
      our results. METHODS: Within the German IDA study ('Dementia Care Initiative in
      Primary Practice'), informal care time for people with dementia living at home is
      assessed. We applied a German adaptation of the Resource Utilization in Dementia
      (RUD) questions on informal care, which distinguishes three categories of
      informal care activities: Activities of Daily Living (ADL), Instrumental ADL
      (IADL), and supervision. In contrast to the original version, we included the
      time of all informal caregivers who are involved in caring for the patient. The
      questionnaire was completed as a computer-assisted telephone interview at
      baseline and after 1 year. To test the plausibility of the questionnaire, we
      proposed seven hypotheses about the reported informal care time. RESULTS: Nearly
      all results confirmed our hypotheses. Informal care time as well as changes over
      time correlated with the physical and mental health status of the patient.
      Considering the time of other informal caregivers led to slightly higher
      correlations (not significant). The results indicate that interviewees seem to
      underestimate particularly the time of supervision of other informal caregivers.
      CONCLUSION: In sum, the instrument gives plausible results and is suited for
      measuring informal care time, as well as changes over time. If it is not possible
      to directly interview each caregiver involved, it is of great importance to
      identify and interview the primary informal caregiver in order to prevent an
      underestimation of total informal care time.

PMID- 18727141
TI  - Ion mobility adds an additional dimension to mass spectrometric analysis of
      solution-phase hydrogen/deuterium exchange.
AB  - The goal of this study was to determine the utility of adding ion mobility
      spectrometry to studies probing the solution-phase hydrogen/deuterium exchange
      (HX) of proteins. The HX profile of the Hck SH3 domain was measured at both the
      intact protein and the peptic peptide levels in the Waters Synapt HDMS system
      which uses a traveling wave to accomplish ion mobility separation prior to time
      of-flight (Tof) m/z analysis. The results indicated a similar loss of deuterium
      with or without use of mobility in the Synapt and a level of deuterium loss
      comparable with a non-mobility Q-Tof instrument. The drift time of this small
      protein and its peptic peptides did not noticeably change due to solution-based
      deuterium incorporation. Importantly, ion mobility separations provided an
      orthogonal dimension of separation in addition to the reversed-phase high
      performance liquid chromatography (RP-HPLC). The additional dimension of
      separation allowed for the deconvolution of overlapping isotopic patterns for co
      eluting peptides and extraction of valuable deuterium incorporation data for
      those peptides. Taken together, these results indicate that including ion
      mobility separation in HX MS analyses further improves the mass spectrometry
      portion of such experiments.

PMID- 18727142
TI  - Robotic choledochojejunostomy with intracorporeal Roux limb construction.
AB  - BACKGROUND: Biliary surgery can often be very complex, with difficult access
      issues, small structures to be manipulated and sutured and proximity to major
      vessels. Additionally, biliary surgery is often reoperative. All of these issues
      have the potential to be aided by the use of technology which provides three
      dimensional (3D) vision, excellent illumination and access, with steady
      instrument control under maximal magnification. The robot is such a technology
      which is currently available. METHODS: The Da Vinci robot was used to perform a
      robotic choledochojejunostomy, using five ports and a totally intracorporeal
      technique. RESULTS: Two patients were studied. There were no conversions to open
      operation. There was no mortality. One patient experienced a postoperative bile
      leak, which was successfully managed endoscopically. CONCLUSIONS: Robotic
      choledochojejunostomy with intracorporeal Roux-en-Y anastomosis is a feasible
      operation with a definite learning curve. It has potential benefits to the
      patient.

PMID- 18727143
TI  - The association of individual and facility characteristics with psychiatric
      hospitalization among nursing home residents.
AB  - OBJECTIVE: To examine resident and facility characteristics associated with
      psychiatric hospitalizations (PH) for Medicaid enrolled nursing home (NH)
      residents. METHODS: Participants were all Medicaid enrolled NH residents (n =
      32,604) from all Medicaid certified nursing homes in Florida (n = 584) with
      complete data. We used individual demographic and diagnostic characteristics, as
      well as facility characteristics, to explore risk of psychiatric hospitalization
      in this dataset. RESULTS: Using generalized estimating equations, we found that
      younger age, male gender, poor physical health, serious mental illness, dementia,
      and drug use disorder were associated with risk of psychiatric hospitalization.
      Most notably, residents under 65 were more than three times more likely to
      undergo psychiatric hospitalization and dementia was associated with a three-fold
      increase in the risk of psychiatric hospitalization. Predictors of PH differed
      somewhat for younger and older residents. Among facility characteristics, greater
      facility size, low proportion of those paying via Medicare and high proportion of
      residents with serious mental illness were associated with increased risk of
      psychiatric hospitalization, whereas, low proportion of residents paying via
      Medicaid, high proportion of residents paying via Medicare, and low proportion of
      resident with serious mental illness were associated with reduced risk.
      CONCLUSIONS: Both resident and facility characteristics impact risk for
      psychiatric hospitalization. Attention to identified predictors may reduce risk
      and improve outcomes for nursing home residents.

PMID- 18727144
TI  - Global gene expression profile of Saccharomyces cerevisiae induced by dictamnine.
AB  - Dictamnine, a natural plant product, has been reported to have antimicrobial
      activity against bacteria and fungi; however, the dictamnine response mechanisms
      of microorganisms are still poorly understood. We have shown that dictamnine has
      antimicrobial activities against the model fungus Saccharomyces cerevisiae, with
      a minimum inhibitory concentration (MIC) value of 64 microg/ml. Commercial
      oligonucleotide microarrays were used to determine the global transcriptional
      response of S. cerevisiae triggered by treatment with dictamnine. We interpreted
      our microarray data using the hierarchical clustering tool, T-profiler. Several
      major transcriptional responses were induced by dictamnine. The first was the
      induced environmental stress response, mainly under the control of the Msn2p and
      Msn4p transcription factors, and the repressed environmental stress response in
      genes containing the PAC (RNA polymerase A and C box) and rRPE (ribosomal RNA
      processing element) motifs. The second was the Upc2p-mediated response involved
      in lipid biosynthesis. The third comprised the PDR3- and RPN4-mediated responses
      involved in multidrug resistance (MDR). Finally, the TBP-mediated response was
      induced with dictamnine treatment. TBP is an essential general transcription
      factor involved in directing the transcription of genes. Quantitative real-time
      RT-PCR was performed on selected genes to verify the microarray results.
      Furthermore, morphological transitions during dictamnine exposure to S.
      cerevisiae L1190 (MATa/alpha) were examined, using confocal laser microscopy.

PMID- 18727145
TI  - Photoactivatable GFP tagging cassettes for protein-tracking studies in the
      budding yeast Saccharomyces cerevisiae.
AB  - Yeast cell biologists use a variety of fluorescent protein tags for determining
      protein localization and for measuring protein dynamics using fluorescence
      recovery after photobleaching (FRAP). Although many modern fluorescent proteins,
      such as those with photoactivatable and photoconvertible characteristics, have
      been developed, none has been exploited for studies in budding yeast. We describe
      here the construction of yeast-tagging vectors containing photoactivatable green
      fluorescent protein (PA-GFP) for analysis of protein behaviour. We tagged two
      yeast proteins, Erg6p and Num1p, with PA-GFP and demonstrated specific
      photoactivation of the fusion proteins in live cells. Fluorescence intensity
      measurements showed that a short 5 s exposure to 413 nm light is sufficient to
      produce the maximum level of activated GFP fluorescence. Local photoactivation of
      cortical Num1p-PA-GFP showed movement of the marked proteins, providing new
      insights into the behaviour of Num1p at the cell cortex. Since photoactivation
      can be achieved using standard mercury arc illumination, the PA-GFP tag
      represents a convenient and economical way to determine protein dynamics in the
      cell. Thus, the tagging modules should facilitate protein-tracking studies in a
      wide variety of cell biological processes in yeast.

PMID- 18727146
TI  - Exometabolic and transcriptional response in relation to phenotype and gene copy
      number in respiration-related deletion mutants of S. cerevisiae.
AB  - The transcriptional and metabolic impact of deleting one or both copies of a
      respiration-related gene has been studied in glucose-limited chemostats.
      Integration of literature information on phenotype with our exometabolome and
      transcriptome data enabled the identification of novel relationships between gene
      copy number, transcriptional regulation and phenotype. We found that the effect
      of complete respiratory deficiency on transcription was limited to downregulation
      of genes involved in oxidoreductase activity and iron assimilation. Partial
      respiratory deficiency had no significant impact on gene transcription. Changes
      in the copy number of two transcription-factor genes, HAP4 and MIG1, had a major
      impact on genes involved in mitochondrial function. Regulation of respiratory
      chain components encoded in the nucleus and mitochondria appears to be divided
      between Hap4p and Oxa1p, respectively. Similarly, repression of respiration may
      be imposed by the action of Mig1p and Mba1p on nuclear and mitochondrial gene
      expression, respectively. However, it is not clear whether Oxa1p and Mba1p
      regulate mitochondrial gene expression via their interaction with mitochondrial
      ribosomes or by some indirect means. The phenotype of nuclear petite mutants may
      not simply be due to the absence of respiration; e.g. Oxa1p or Bcs1p may play a
      role in the regulation of ribosome assembly in the nucleolus. Integration between
      respiration and cell growth may also result from the action of a single
      transcription factor. Thus, Hap4p targets genes that are required for respiration
      and for fitness in nutrient-limited conditions. This suggests that Hap4p may
      enable cells to adapt to nutrient limitation as well as diauxy.

PMID- 18727147
TI  - Does dementia predict adverse hospitalization outcomes? A prospective study in
      aged inpatients.
AB  - BACKGROUND: Dementia is often considered a predictor of adverse hospitalization
      outcomes. However, the relative contributions of dementia and other risk factors
      remain unclear. OBJECTIVE: To assess, in a prospective study, the relative value
      of dementia for predicting hospitalization outcomes, taking into account
      comorbidity, functional and nutritional status in 435 inpatients (age 85.3 +/-
      6.7; 207 cognitively normal, 48 with mild cognitive impairment and 180 demented)
      from the acute and rehabilitation geriatric hospital of Geneva. Hospitalization
      outcomes (death in hospital, length of stay, institutionalisation and formal home
      care needs) were predicted using logistic regression models with sociodemographic
      characteristics, cognitive status, comorbid Charlson index-CCI, functional and
      nutritional status as independent variables. RESULTS: Moderate and severe
      dementia and poor physical function strongly predicted longer hospital stay,
      institutionalization and greater home care needs in univariate analyses. CCI was
      the best single predictor, with a four-fold difference in mortality rates between
      the highest and lowest scores. In multivariate analysis, the best predictor of
      institutionalisation was dementia, whereas the best predictor of death in
      hospital or longer hospital stay was higher comorbidity score, regardless of
      cognitive status. Functional status was the best predictor of greater home care
      needs. CONCLUSIONS: Dementia in very old medically ill inpatients was predictive
      only of discharge to a nursing home. Higher levels of comorbidity and poor
      functional status were more predictive than dementia for the other three
      hospitalization outcomes. Thus, comorbid medical conditions, functional and
      nutritional status should be considered, together with cognitive assessment, when
      predicting hospitalization outcome.

PMID- 18727148
TI  - An efficient soft tissue characterization algorithm from in vivo indentation
      experiments for medical simulation.
AB  - BACKGROUND: Realistic virtual reality surgical training simulators require an
      accurate biomechanical model of in vivo soft tissue behaviour. One of the
      challenges in modelling is to characterize soft tissue properties incorporating
      the experimental measurements of organ behaviour. METHOD: Organ measurements were
      collected from intra-abdominal organs of pigs, using a robotic indenter and a
      force transducer. The constitutive model was fitted to the in vivo data using the
      Levenberg-Marquardt optimization algorithm, combined with a three-dimensional non
      linear finite element (FE) simulation. RESULTS: This paper presents an integrated
      framework for measuring, modelling and calibrating organs' material properties
      and provides parameters for modelling pigs' intra-abdominal organs. CONCLUSION:
      The calibrated mechanical models are suitable for computing accurate reaction
      forces on surgical instruments and for computing the deformations of organs. They
      also provide a useful benchmark for measuring the realism of real-time tissue
      models used in virtual reality-based surgical trainers.

PMID- 18727149
TI  - Incorporation of carbon and nitrogen atoms into proteins measured by protein
      based stable isotope probing (Protein-SIP).
AB  - The identification of metabolically active microbial key players is fundamental
      for understanding the structure and functions of contaminant-degrading
      communities. The metabolic activity can be analysed by feeding the microbial
      culture with stable-isotope-labelled substrates and subsequently tracing their
      incorporation into the biomass. In this paper we present a method which is able
      to detect the incorporation of stable isotopes from the substrate into the
      proteins of a benzene-metabolising microorganism. Pseudomonas putida strain ML2
      was grown under aerobic conditions with the substrates (12)C-benzene, (13)C
      benzene or (15)N-ammonium and (12)C-benzene. Proteins of these cultures were
      resolved by two-dimensional gel electrophoresis (2-DE) and corresponding protein
      spots were subjected to matrix-assisted laser ionization/desorption mass
      spectrometric (MALDI-MS) analysis. The proteins of the (12)C-sample were
      identified by peptide mass fingerprinting (PMF) as well as by tandem mass
      spectrometric (MS/MS) measurements. The (13)C- or (15)N-content of the peptides
      from the labelling experiments was determined by MALDI-MS/MS. The incorporation
      of heavy isotopes into the proteins from cultures grown on (13)C-benzene and
      (15)N-ammonium was determined based on the mass differences between labelled and
      non-labelled peptides as well as on the isotopic distribution of the y(1)-ion of
      arginine. The method we present here principally allows the unravelling of the
      carbon and nitrogen flow not only in pure cultures, but also in microbial
      communities consisting of many microbial species.

PMID- 18727150
TI  - Effect of age and food intake on dietary carbon turnover recorded in sheep wool.
AB  - We present the results of a series of controlled feeding experiments with sheep,
      designed to investigate the effects of age and level of food intake on the
      kinetics of incorporation of the dietary carbon signal into wool. Four different
      groups of three sheep each, ranging in age from 6 to 78 months, were fed a C(3)
      diet and switched to a C(4) diet for up to 250 days. Different quantities of the
      same C(4) diet were provided to each group, in order to achieve different growth
      rates (high, low, and no growth). Wool was repeatedly shorn from each animal and
      processed for delta(13)C analyses. Results show that newly grown wool does not
      start recording the isotope composition of the new diet immediately after the
      diet-switch. The time-lag varies according to the age of the animal, from 6 +/- 1
      days in lambs to up to 15 +/- 4 days in the older ewes. Wool from fast-growing
      lambs approached equilibrium faster than that from slow-growing lambs and young
      ewes, with old ewes being the slowest. However, 3 weeks after the diet-switch,
      the differences in wool delta(13)C values between the four different groups of
      animals were relatively small and represented less than 15% of the isotopic
      difference between the two diets. These results suggest that a single equation
      can be used to reconstruct previous diets for animals of different age, provided
      that the diet is similar and all individuals are in positive protein balance.

PMID- 18727151
TI  - First-pass dynamic contrast-enhanced MRI with extravasating contrast reagent:
      evidence for human myocardial capillary recruitment in adenosine-induced
      hyperemia.
AB  - Human myocardial (1)H(2)O T(1)-weighted dynamic contrast-enhanced MRI data were
      acquired during the brief first-pass period after injection of a very small
      gadolinium diethylenetriaminepenta-acetate (GdDTPA(2-)) dose. The shutter-speed
      pharmacokinetic effects of both transendothelial and transcytolemmal equilibrium
      water exchange processes were investigated. Our results indicate that even for
      such a short acquisition window and relatively large pseudo-first-order rate
      constant (K(trans)) for plasma/interstitium contrast reagent (CR) transfer the
      kinetics of these water exchange processes cannot be treated as infinitely fast
      or slow. However, neither the intracellular water molecule lifetime (tau(i)) nor
      its intravascular counterpart (tau(b)) are among the parameters most influential
      in analysis of the noisy data typically associated with the cardiac perfusion
      application. Thus, the actual values of water exchange kinetic rate constants are
      relatively indeterminate as this experiment is usually conducted. Combining the
      K(trans) evaluations with independently determined flow (F) values allows us to
      estimate CR permeability coefficient surface area product (P(CR)S) values. The
      fact that the P(CR)S magnitudes almost equal the K(trans) values confirms that
      GdDTPA(2-) extravasation in resting human myocardial muscle is indeed permeation
      limited and supports the validity of the K(trans) and P(CR)S estimations.
      Nevertheless the model analysis is most consistent with the results if P(CR)S is
      not assumed to be constant with changing flow. The capillary blood volume
      fraction (v(b)) is a sensitive parameter in the analysis. We also compared
      resting and hyperemic cardiac conditions, the latter resulting from the volume
      flow increase induced by adenosine arteriolar vasodilation. We found that the
      P(CR)S value increases with flow probably mostly because of an S increase
      associated with capillary recruitment. The v(b) values also increased in
      hyperemia and showed a flow-dependence with a clearly identifiable component due
      to capillary recruitment.

PMID- 18727152
TI  - The gap-filling sequence on the left arm of chromosome 2 in fission yeast
      Schizosaccharomyces pombe.
AB  - We report a gap-filling sequence between SPBPB21E7.09 (in contig c1348) and
      SPBPB10D8.01 (in contig pB10D8) on the left arm of chromosome 2 in the fission
      yeast, Schizosaccharomyces pombe. The sequence was determined from a BAC clone
      overlapping SPBPB21E7.01c (eno102) (in contig c1348) and SPBC1683.07 (mal1) (in
      contig pB10D8). The gap-filling sequence is 17,881 bp in length and contains five
      putative open reading frames, which were systematically named as SPBC460.01c,
      SPBC460.02c, SPBC460.03, SPBC460.04c and SPBC460.05. Their deduced amino acid
      sequences respectively include protein motifs corresponding to amino acid
      permease, glutathione S-transferase C-terminal domain, taurine catabolism
      dioxygenase TauD TfdA family and major facilitator superfamily, whereas their
      functions are unknown.

PMID- 18727153
TI  - Bone marrow or foetal liver cells fail to induce islet regeneration in diabetic
      Akita mice.
AB  - BACKGROUND: In this study, we carried out bone marrow and foetal liver cell
      transplantation to determine if these cells could differentiate into pancreatic
      beta-cells or promote regeneration. METHODS: To exclude an artificial or
      immunological influence for induction of diabetes to recipients, Akita mice,
      which develop diabetes spontaneously,were used. In addition, we used mice
      harbouring the transgenic green fluorescent protein (GFP) reporter for insulin 1
      gene as donors to mark donor-derived beta-cells. RESULTS: All transplanted Akita
      mice after intravenous injection showed full donor chimerism in peripheral blood
      analysis. Their diabetic state represented by blood glucose levels did not change
      after transplantation. In spite of examination of more than 200 islets in each
      group, we could not find GFP-positive cells in any of the recipients.
      CONCLUSIONS: Bone marrow cells or foetal liver cells do not differentiate to new
      pancreatic beta-cells or promote regeneration in Akita mice, a non-chemical or
      non-immune model of diabetes.

PMID- 18727154
TI  - QM/QM docking method based on the variational finite localized molecular orbital
      approximation.
AB  - We present a derivation of the semiempirical variational finite localized
      molecular orbital (VFL) approximation, which was introduced by Anikin et al. (J
      Chem Phys 2004, 121, 1266). On the basis of VFL approximation, we developed the
      novel semiempirical (quantum mechanical) QM/QM method in which a part of the
      system, including the ligand and protein active site, are treated self
      consistently, while the protein bulk is considered as carrying a frozen
      electronic density matrix. The developed method is applied toward the QM docking
      study for the p56 LCK SH2 domain. The virtual search has predicted 10 most potent
      inhibitors by searching through the database of 200,000 empirically docked poses
      of 20,000 drug-like molecules. Energy score calculation of each complex roughly
      consisting of 1700 atoms took 14.54 s of single-CPU time at the NDDO AM1 level.
      The entire computation performed on a 32-CPU cluster would be accomplished in 1
      day. Flexible ligand QM docking studies, performed on a subset of 10,000 poses,
      required 153.03 s of single-CPU time per complex. The entire calculation
      performed on the 32-CPU cluster would be finished in half-day.

PMID- 18727155
TI  - Application of error-ranked singular value decomposition for the determination of
      potential-derived atomic-centered point charges.
AB  - The present work provides a detailed investigation on the use of singular value
      decomposition (SVD) to solve the linear least-squares problem (LLS) for the
      purposes of obtaining potential-derived atom-centered point charges (PD charges)
      from the ab initio molecular electrostatic potential (V(QM)). Given the SVD of
      any PD charge calculation LLS problem, it was concluded that (1) all singular
      vectors are not necessary to obtain the optimal set of PD charges and (2) the
      most effective set of singular vectors do not necessarily correspond to those
      with the largest singular values. It is shown that the efficient use of singular
      vectors can provide statistically well-defined PD charges when compared with
      conventional PD charge calculation methods without sacrificing the agreement with
      V(QM). As can be expected, the methodology outlined here is independent of the
      algorithm for sampling V(QM) as well as the basis set used to calculate V(QM). An
      algorithm is provided to select the best set of singular vectors used for optimal
      PD charge calculations. To minimize the subjective comparisons of different PD
      charge sets, we also provide an objective criterion for determining if two sets
      of PD charges are significantly different from one another.

PMID- 18727156
TI  - Application of the dressed time-dependent density functional theory for the
      excited states of linear polyenes.
AB  - Dressed Time-Dependent Density Functional Theory (Maitra et al., J Chem Phys
      2004, 120, 5932) is applied to selected linear polyenes. Limits of validity of
      the approximation are briefly discussed. The implementation strategy is
      described. Results for the 2(1)B(u) and 2(1)A(g) states of selected linear
      polyenes are presented and compared with accessible experimental and theoretical
      results.

PMID- 18727157
TI  - Prediction of acidity in acetonitrile solution with COSMO-RS.
AB  - The COSMO-RS method, a combination of the quantum chemical dielectric continuum
      solvation model COSMO with a statistical thermodynamics treatment for realistic
      solvation simulations, has been used for the prediction of pK(a) values in
      acetonitrile. For a variety of 93 organic acids, the directly calculated values
      of the free energies of dissociation in acetonitrile showed a very good
      correlation with the pK(a) values (r(2) = 0.97) in acetonitrile, corresponding to
      a standard deviation of 1.38 pK(a) units. Thus, we have a prediction method for
      acetonitrile pK(a) with the intercept and the slope as the only adjusted
      parameters. Furthermore, the pK(a) values of CH acids yielding large anions with
      delocalized charge can be predicted with a rmse of 1.12 pK(a) units using the
      theoretical values of slope and intercept resulting in truly ab initio pK(a)
      prediction. In contrast to our previous findings on aqueous acidity predictions
      the slope of the experimental pK(a) versus theoretical DeltaG(diss) was found to
      match the theoretical value 1/RT ln (10) very well. The predictivity of the
      presented method is general and is not restricted to certain compound classes.
      However, a systematic correction of -7.5 kcal mol(-1) is required for compounds
      that do not allow electron-delocalization in the dissociated anion. The
      prediction model was tested on a diverse test set of 129 complex multifunctional
      compounds from various sources, reaching a root mean square deviation of 2.10
      pK(a) units.

PMID- 18727158
TI  - Implementation and use of a direct, partially integral-driven non-Dyson
      propagator method for molecular ionization.
AB  - The Green's function ADC(3) scheme has been for many years a successful method to
      predict theoretically the ionization (and electron affinity) spectrum of
      molecules. However, a dramatic enhancement of the method's power has come only
      recently, with the development of an approximation method to the one-particle
      Green's function which does not make direct use of the Dyson equation. In the
      present work, we present an efficient computer implementation of this novel
      approach, with first comparative tests demonstrating its enormous computational
      advantage over the conventional approach.

PMID- 18727159
TI  - Parallel Fock matrix construction program for molecular orbital calculation-
      specific computer with a hierarchical network.
AB  - A parallel Fock matrix construction program for a hierarchical network has been
      developed on the molecular orbital calculation-specific EHPC system. To obtain
      high parallelization efficiency on the hierarchical network system, a multilevel
      dynamic load-balancing scheme was adopted, which provides equal load balance and
      localization of communications on a tree-structured hierarchical network. The
      parallelized Fock matrix construction routine was implemented into a GAMESS
      program on the EHPC system, which has a tree-structured hierarchical network.
      Benchmark results on a 63-processor system showed high parallelization efficiency
      even on the tree-structured hierarchical network.

PMID- 18727160
TI  - Ab initio calculations on halogen-bonded complexes and comparison with density
      functional methods.
AB  - A systematic theoretical investigation on a series of dimeric complexes formed
      between some halocarbon molecules and electron donors has been carried out by
      employing both ab initio and density functional methods. Full geometry
      optimizations are performed at the Moller-Plesset second-order perturbation (MP2)
      level of theory with the Dunning's correlation-consistent basis set, aug-cc-pVDZ.
      Binding energies are extrapolated to the complete basis set (CBS) limit by means
      of two most commonly used extrapolation methods and the aug-cc-pVXZ (X = D, T, Q)
      basis sets series. The coupled cluster with single, double, and noniterative
      triple excitations [CCSD(T)] correction term, determined as a difference between
      CCSD(T) and MP2 binding energies, is estimated with the aug-cc-pVDZ basis set. In
      general, the inclusion of higher-order electron correlation effects leads to a
      repulsive correction with respect to those predicted at the MP2 level. The
      calculations described herein have shown that the CCSD(T) CBS limits yield
      binding energies with a range of -0.89 to -4.38 kcal/mol for the halogen-bonded
      complexes under study. The performance of several density functional theory (DFT)
      methods has been evaluated comparing the results with those obtained from MP2 and
      CCSD(T). It is shown that PBEKCIS, B97-1, and MPWLYP functionals provide
      accuracies close to the computationally very expensive ab initio methods.

PMID- 18727161
TI  - PhAST: pharmacophore alignment search tool.
AB  - We present a ligand-based virtual screening technique (PhAST) for rapid hit and
      lead structure searching in large compound databases. Molecules are represented
      as strings encoding the distribution of pharmacophoric features on the molecular
      graph. In contrast to other text-based methods using SMILES strings, we introduce
      a new form of text representation that describes the pharmacophore of molecules.
      This string representation opens the opportunity for revealing functional
      similarity between molecules by sequence alignment techniques in analogy to
      homology searching in protein or nucleic acid sequence databases. We favorably
      compared PhAST with other current ligand-based virtual screening methods in a
      retrospective analysis using the BEDROC metric. In a prospective application,
      PhAST identified two novel inhibitors of 5-lipoxygenase product formation with
      minimal experimental effort. This outcome demonstrates the applicability of PhAST
      to drug discovery projects and provides an innovative concept of sequence-based
      compound screening with substantial scaffold hopping potential.

PMID- 18727162
TI  - Effects of acidification on carbon and nitrogen stable isotopes of benthic
      macrofauna from a tropical coral reef.
AB  - Stable isotope analyses are widely used to determine trophic levels in ecological
      studies. We have investigated the effects of carbonate removal via acidification
      on the stable carbon and nitrogen isotopic composition of 33 species of tropical
      benthic macrofauna, and we report guidelines for standardizing this procedure for
      higher taxa in tropical coral reef ecosystems. Many tropical benthic
      invertebrates are small in size, and therefore body tissue isolation (separating
      organic carbon from inorganic structures) is difficult and time-consuming.
      Literature reviews of invertebrate studies show a lack of consistent procedures
      and guidelines for preparation techniques, especially for carbonate removal via
      acidification of whole individuals. We find that acidification decreases the
      delta(13)C values of samples containing carbonate, with shifts ranging from 0.21
      to 3.20 per thousand, which can be related to CaCO(3) content (assessed by a
      carbonate proxy), justifying acid pre-treatment. Carbonate-containing taxa
      benefiting from acidification included Amphinomida, Terebellida (Annelida),
      Anomura, Brachyura, Caridea, Amphipoda, Tanaidacea (Arthropoda) and Edwardsiida
      (Cnidaria). The delta(13)C shifts of samples containing no carbonate varied up to
      0.02 +/- 0.20 per thousand. As this induced delta(13)C shift was lower than the
      range of an average trophic level shift (0.5 to 1 per thousand), we conclude that
      acid pre-treatment is unnecessary. Carbonate-free taxa consisted of Eunicida,
      Phyllodocida (Annelida) and Mollusca. We note minimal impact of acidification on
      delta(15)N values except for Brachyura, which showed a shift of 0.83 +/- 0.46 per
      thousand, which is still lower than a single trophic level shift (2.9-3.8 per
      thousand). We conclude that for trophic level studies, both the delta(13)C and
      the delta(15)N of carbonate-rich macrofauna can be determined from the same
      acidified sample.

PMID- 18727163
TI  - Complete 1H and 13C data assignments of two new guaianolides isolated from
      Ainsliaea fragrans.
AB  - Two new guaianolides, 8alpha-hydroxy-11alpha,13-dihydroglucozaluzanin C and
      11alpha,13-dihydroglucozaluzanin C, were isolated from Ainsliaea fragrans, along
      with two known guaianolides, 8alpha-hydroxy-11alpha,13-dihydrozaluzanin C and
      glucozaluzanin C. The structures of the new compounds were unambiguously
      established by HR-ESI-MS, one-dimensional (1D) (DEPT), two-dimensional (2D) ((1)H
      (1)H COSY, HSQC, HMBC, ROESY) NMR experiments and by comparison with structurally
      related compounds. The known compounds were identified by comparison of spectral
      data with published references. Some NMR data of the known compounds were
      reported for the first time.

PMID- 18727164
TI  - Diffusion-weighted imaging of the entire spinal cord.
AB  - In spite of their diagnostic potential, the poor quality of available diffusion
      weighted spinal cord images often restricts clinical application to cervical
      regions, and improved spatial resolution is highly desirable. To address these
      needs, a novel technique based on the combination of two recently presented
      reduced field-of-view approaches is proposed, enabling high-resolution
      acquisition over the entire spinal cord. Field-of-view reduction is achieved by
      the application of non-coplanar excitation and refocusing pulses combined with
      outer volume suppression for removal of unwanted transition zones. The non
      coplanar excitation is performed such that a gap-less volume is acquired in a
      dedicated interleaved slice order within two repetition times. The resulting
      inner volume selectivity was evaluated in vitro. In vivo diffusion tensor imaging
      data on the cervical, thoracic and lumbar spinal cord were acquired in transverse
      orientation in each of four healthy subjects. An in-plane resolution of 0.7 x 0.7
      mm(2) was achieved without notable aliasing, motion or susceptibility artifacts.
      The measured mean +/- SD fractional anisotropy was 0.69 +/- 0.11 in the thoracic
      spinal cord and 0.75 +/- 0.07 and 0.63 +/- 0.08 in cervical and lumbar white
      matter, respectively.

PMID- 18727165
TI  - Minimising the effects of bolus dispersion in bolus-tracking MRI.
AB  - Bolus-tracking perfusion measurements in patients with vascular abnormalities are
      often unreliable, because delay and/or dispersion of the bolus within the vessels
      distorts the measured arterial input function (AIF). Erroneous measurements of
      perfusion can be identified by examining the measured response function, the
      shape of which is determined by both the tissue and arterial retention. In this
      work, an accurate response function is extracted by combining maximum-likelihood
      expectation-maximisation deconvolution, regularised using an oscillation index,
      with subsequent wavelet thresholding. Simulations show that this method recovers
      both the smooth-dispersed and the sharp-delayed response functions. This enables
      regions where the bolus is delayed and/or dispersed to be identified when the
      methodology is applied to data from patients with vascular abnormalities.
      Simulations also demonstrate robust and accurate perfusion estimates when there
      is no bolus delay and/or dispersion. The presence of delay and/or dispersion in
      the response function suggests that the perfusion measurements are erroneous, and
      that the global AIF is an inaccurate approximation to the true AIF in these
      regions. Perfusion measurements are corrected within the affected regions by
      defining a regional AIF from the independent component analysis of the dynamic
      susceptibility contrast MRI data. The regional AIF is shown to remove the delay
      and dispersion, improving the accuracy of the perfusion maps.

PMID- 18727166
TI  - Study suggests bipolar disorder is overdiagnosed.

PMID- 18727167
TI  - Psychotherapy for early childhood obsessive-compulsive disorder.

PMID- 18727169
TI  - Exposure.  Claim over contaminated transplant tissue fails.

PMID- 18727168
TI  - Federal government   diverts funding from   community-based organizations   to
      vaccine initiative.

PMID- 18727170
TI  - Missed HIV medications in prison fail to rise to violation.

PMID- 18727171
TI  - Asylum.  Review of removal order for HIV-positive Colombians denied.

PMID- 18727172
TI  - HIV diagnosis fails as defense for probation violations.

PMID- 18727173
TI  - FDA notifications. Lopinavir/ritonavir label updated.

PMID- 18727174
TI  - FDA notifications. Tentative approval granted for lamivudine/stavudine.

PMID- 18727175
TI  - With long hours, less staff nurses fear needlesticks. ANA survey finds infections
      remain major concern.

PMID- 18727176
TI  - Risk factors for infection with extended-spectrum and AmpC beta-lactamase
      producing gram-negative rods in renal transplantation.
AB  - Increasing prevalence of infections caused by multiresistant gram-negative
      enteric bacilli due to synthesis of extended-spectrum beta-lactamase (ESBL) or to
      desrepressed chromosomic AmpC beta-lactamase (AmpC) is a major concern in the
      hospitalized patient population. Renal transplant recipients are especially
      susceptible to these infections. A cohort observational study in a 3-year period
      was performed. ESBL-production was determined by phenotypic analysis based on the
      CLSI recommendations. A multi-variate logistic regression analysis was performed
      to identify independent variables associated with multi-resistant gram-negative
      bacilli infection. The study included 417 patients (61 double kidney-pancreas
      recipients). The incidence of ESBL-producing and desrepressed chromosomic AmpC
      beta-lactamase resistance was 11.8% (49 patients). The most frequent bacteria
      isolated was E. coli (35/60 isolations), followed by Klebsiella spp(12/60
      isolations). Double kidney-pancreas transplantation(OR 3.5, CI95% 1.6-7.8),
      previous use of antibiotics(OR 2.1,CI95% 1.1-4.1), posttransplant dialysis
      requirement (OR 3.1, CI95% 1.5-6.4) and posttransplant urinary obstruction (OR
      5.8, CI95% 2.2-14.9) were independent variables associated with these
      multiresistant gram-negative enteric bacilli infections. The incidence of ESBL
      producing and desrepressed AmpC beta-lactamase gram-negative enteric bacilli
      infection in our population was high. These infections are associated with
      significant morbidity after renal transplantation.

PMID- 18727177
TI  - Re: Chiropractic: a critical evaluation.

PMID- 18727178
TI  - Haiti's forgotten emergency.

PMID- 18727179
TI  - The diplomatic library.

PMID- 18727180
TI  - Mercury spill control 101.

PMID- 18727181
TI  - Did not attends: who, why, when?

PMID- 18727182
TI  - Decrease your cancer risk with weight control and lifestyle changes.  Simple
      changes in how you live can increase your chances of longevity.

PMID- 18727183
TI  - DASH redux: diet shows reduced risk of heart disease and stroke. The 11-year-old
      diet that successfully lowers blood pressure and cholesterol now shows other
      benefits.

PMID- 18727184
TI  - Polyvascular disease: the systemic nature of atherosclerosis. The greater the
      number of sites affected, the greater the risk of major cardiac event. Take steps
      to lower your odds.

PMID- 18727185
TI  - Duke leads the way in joint replacement surgery. Improved materials and advanced
      surgical techniques result in less pain, increased function and improved implant
      survival.

PMID- 18727186
TI  - New surgical procedure provides chronic headache relief. Peripheral cranial nerve
      stimulation blocks pain signals from reaching the brain.

PMID- 18727187
TI  - Surgery may be best choice for spinal stenosis. But medication and physical
      therapy also can alleviate the condition without worsening it.

PMID- 18727188
TI  - What is the significance of "rheumatoid nodules?" I have a growing nodule on the
      outer surface of of my arm. Two doctors told me they are rheumatoid nodules, but
      another says they are benign tumors of the tendon sheath. They are unsightly, but
      I don't want to go under anesthesia to have them removed. If they are RA nodules,
      could they appear in any other area of my body?

PMID- 18727189
TI  - Thailand: government re-launches war   on drugs and people who use drugs.
AB  - On 2 April 2008, Thailand Prime Minister Samak Sundarajev announced a new
      national drug strategy. Called "Thai Power, To Avoid the Danger of Drugs," the
      strategy is intended to run for six months (from April to September 2008) and
      includes a number of activities designed to reduce the number of people who use
      drugs in Thailand.

PMID- 18727190
TI  - Switzerland: statement on sexual transmission of HIV by people on ART.
AB  - In February 2006, Swiss experts issued a statement concluding that HIV-positive
      individuals who are on effective antiretroviral therapy (ART), and who do not
      have any sexually transmitted infections (STIs), cannot transmit HIV through
      sexual contact. The statement was authored by four of Switzerland's leading AIDS
      experts and was issued on behalf of the Swiss Federal Commission for HIV/AIDS.

PMID- 18727191
TI  - U.S.: PEPFAR reauthorization bills pass House, Senate committee.
AB  - On 2 April 2008, the U.S. House of Representatives passed a bill (H.R. 5501) to
      reauthorize the President's Emergency Plan for AIDS Relief (PEPFAR). The House
      bill would authorize the appropriation of US$50 billion over the next five years-
      40 percent more than the US$30 billion requested by President George W. Bush.

PMID- 18727192
TI  - HIV and human rights in U.N. drug   control policy: making inroads, barely.
AB  - Each year, U.N. member states gather for a week in Vienna at the Commission on
      Narcotic Drugs (CND), the central policy-making body within the U.N. system
      dealing with drug-related matters, "to exchange expertise, experiences and
      information on drug-related matters and to collaborate on a coordinated response
      to the global drug situation."

PMID- 18727193
TI  - Russia denies HIV   treatment to prisoner.

PMID- 18727194
TI  - ILO publishes digest of   good legislative practices   in Africa.

PMID- 18727195
TI  - U.N. Secretary-General   calls for an end to criminal   law approaches to  
      vulnerable populations.

PMID- 18727196
TI  - Refugee claimant's identity as cross-dresser must be considered in assessing
      adequacy of state protection.
AB  - On 11 December 2007, the Federal Court allowed Jose Hernandez's application for
      judicial review of a November 2006 decision by the Refugee Protection Division of
      the Immigration and Refugee Board, which found that the applicant was neither a
      Convention refugee nor a person in need of protection. Hernandez had requested
      that the Board's decision be set aside and the matter referred back to a newly
      constituted panel of the Board for re-determination.

PMID- 18727197
TI  - Case of disclosure of HIV status helps   to clarify privacy law in Ontario.
AB  - A judge in the Ontario Superior Court of Justice has dismissed a breach of
      privacy suit on the basis that the plaintiff failed to prove that the disclosure
      of his HIV status had caused him harm. The judgment set out guidelines for how
      future claims of breach of privacy should be addressed.

PMID- 18727198
TI  - HIV-positive woman's appeal for   absolute discharge dismissed on   grounds of
      public safety.
AB  - On 7 December 2007, the Nova Scotia Court of Appeal dismissed an appeal from a
      June 2007 order of the Nova Scotia Review Board providing that an HIV-positive
      woman, "K.A.S.," be discharged with conditions to reside in hospital-approved
      premises, to continue with recommended mental health treatment, and to abstain
      from alcohol and illicit drug use because she continued to present a significant
      risk to the safety of the public.

PMID- 18727199
TI  - Criminal law and HIV transmission   or exposure: seven new cases.

PMID- 18727200
TI  - Case of HIV-positive gay   transvestite referred to   new refugee panel for   re
      determination.

PMID- 18727201
TI  - Court rules that   defamation not proved   because reputation not   "materially
      affected".

PMID- 18727202
TI  - European Court of Human Rights rejects   prisoner's plea for prison needle
      exchange.
AB  - On 4 January 2008, the European Court of Human Rights declared inadmissible an
      application from prisoner John Shelley alleging a violation of his rights under
      the Convention for the Protection of Human Rights and Fundamental Freedoms
      (European Convention).

PMID- 18727203
TI  - South African High Court  defends the right to water.
AB  - The High Court of South Africa (Witwatersrand Local Division) ruled in April 2008
      that the City of Johannesburg's system for providing water in Phiri, Soweto is
      unconstitutional and unlawful.

PMID- 18727204
TI  - Court says French government's refusal to authorize adoption violates woman's
      human rights.
AB  - On 22 January 2008, the European Court of Human Rights held that there had been a
      violation of the Convention for the Protection of Human Rights and Fundamental
      Freedoms (European Convention) in the case of E.B. v. France, concerning a
      refusal by the French authorities to grant E.B.'s request to adopt a child,
      allegedly on account of her sexual orientation.

PMID- 18727205
TI  - ECHR: Ukraine held   responsible for inhuman   and degrading treatment   of HIV
      positive prisoner.

PMID- 18727206
TI  - U.S.: Texan man   acquitted in medical   marijuana case.

PMID- 18727207
TI  - Indian court rules HIV   is a ground for divorce.

PMID- 18727208
TI  - Characterization of the porcine Kisspeptins receptor gene and evaluation as
      candidate for timing of puberty in sows.
AB  - Kisspeptins receptor (KISS1R), also called GPR54, is a key regulator of puberty
      in many species. KISS1R and its genetics in pigs remain unexplored. The objective
      of this study was to characterize the porcine KISS1R gene and evaluate the
      association of KISS1R mutations with age at puberty in sows. KISS1R was assigned
      to pig chromosome 2q21-24 by radiation hybrid mapping. It has a 1438 bp full
      length cDNA and spans 3349 bp genomic sequence consisting of five exons and four
      introns. Semi-quantitative RT-PCR showed that KISS1R transcripts was particularly
      abundant in the adrenal, prostate, testis, thymus, pituary and hypothalamus.
      KISS1R mRNA content in the hypothalamus was determined by real-time quantitative
      RT-PCR, and it fluctuated during the oestrous cycle with the highest level in the
      luteal phase. Anoestrus sows had markedly lower hypothalamic KISS1R mRNA content
      than cyclic animals. Seven KISS1R SNPs were identified in the founder animals of
      a White Duroc x Erhualian intercross. One missense mutation (T/C(245)) showed
      quite different allele distribution in Chinese and Western breeds. All F(0), F(1)
      animals and 367 detailed phenotyped cyclic F(2) sows in the White Duroc x
      Erhualian intercross were genotyped for three KISS1R polymorphisms. No
      significant association of KISS1R haplotypes and haplotype pairs with age at
      puberty was observed in the resource population, indicating that mutations in
      KISS1R are not responsible for divergent age at puberty in White Duroc and
      Erhualian pigs.

PMID- 18727209
TI  - Plasma leptin levels in pigs with different leptin and leptin receptor genotypes.
AB  - A C3469T mutation at exon 3 of the pig leptin (Lep) gene has been genotyped in
      diverse pig breeds yielding controversial results with regard to its association
      with growth, fatness and carcass traits. A similar situation has been reported
      for a HpaII restriction fragment length polymorphism (RFLP) in the pig leptin
      receptor (Lepr) gene, where associations were found depending on the statistical
      model employed. The main objective of our work was to investigate if leptin
      plasma concentrations differ in pigs with different C3469T and Lepr HpaII RFLP
      genotypes. With this aim, we have measured plasma leptin levels at 160 days in 68
      Landrace pigs with different Lep C3469T and Lepr HpaII RFLP genotypes. Neither
      Lep (TT: 11.68 ng/ml, TC: 10.71 ng/ml) nor Lepr (AA: 12.6 ng/ml, AB: 10.93 ng/ml,
      BB: 11.74 ng/ml) genotypes influenced significantly plasma Lep concentration.
      Moreover, we did not find any association between Lep and Lepr genotypes and
      phenotypic variation at growth and fatness traits in a commercial population of
      320 Landrace pigs.

PMID- 18727210
TI  - Genetic markers for the production of US country hams.
AB  - The objective of this study was to determine the effect of candidate genes on
      processing quality traits of US country hams. A total of 321 fresh hams of
      unknown breed and sex were examined and data on quality and physical traits were
      collected. The hams were then processed following typical US commercial dry
      curing procedures for ham and data on additional traits were collected from the
      cured hams. Several genes involved in biological processes affecting dry-cured
      ham production were selected. Polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) tests were designed for each of the genes where
      polymorphisms were discovered and association analyses between each marker and
      the traits collected were performed. Results showed that two genetic markers were
      significantly associated with cured weight and yield: (i) a gene from the
      cathepsin family (cathepsin F) and (ii) the stearoyl-CoA desaturase (delta-9
      desaturase) gene, involved in lipid metabolism. Moreover, markers that
      significantly affected colour traits and those having a significant impact on pH
      and lipid percentage were also identified. These markers could be used for
      screening and sorting of carcasses prior to ham processing and, eventually in pig
      improvement programmes designed to select animals possessing genotypes more
      suitable for the production of dry-cured hams.

PMID- 18727211
TI  - Study on association of single nucleotide polymorphism of CAPN1 gene with muscle
      fibre and carcass traits in quality chicken populations.
AB  - This study was aimed at investigating the effect of the calpain 1 (CAPN1) gene on
      carcass and meat quality traits in eight meat-type chicken populations, including
      five pure lines (developed from Chinese local breeds) and three cross-breeds.
      Primer pairs for the Coding Sequence (CDS) region in CAPN1 were designed from the
      chicken genomic sequence database. Polymorphisms were detected by polymerase
      chain reaction (PCR)-Single Strand Conformation Polymorphism (SSCP) and DNA
      sequencing. Three single nucleotide polymorphisms (SNP; C2546T, G3535A and
      C7198A) were detected among individuals in each population. The associations of
      their haplotypes (H1 = CGA, H2 = CGC, H3 = CAA, H4 = CAC, H5 = TGA and H7 = TAA)
      with chicken breast muscle fibre and carcass traits were analysed. Results showed
      that the haplotypes were associated with live weight (LW), carcass weight (CW),
      breast muscle weight (BMW) and leg muscle weight (LMW) (p < 0.05), and were also
      related to eviscerated percentage (%EP) and breast muscle fibre density (p <
      0.01). H1H3 haplotype was dominant for LW, CW and BMW; H1H5 haplotype was
      dominant for EP; H3H4 haplotype was dominant for LMW and H1H1 haplotype was
      dominant for BFD. It was concluded that the CAPN1 gene may be a major gene
      affecting meat quality traits of chicken or it is linked with the major gene.
      H1H3, H1H5 and H3H4 were the most advantageous haplotypes for carcass traits
      whereas H1H1 was the positive haplotype for breast muscle fibre trait.

PMID- 18727213
TI  - Polymorphisms of dopamine-beta-hydroxylase in ADHD children.

PMID- 18727212
TI  - Editorial retraction.

PMID- 18727214
TI  - Zingo for local analgesia in children.

PMID- 18727215
TI  - Habitats in submerged karst of Eastern Adriatic coast--Croatian natural heritage.

PMID- 18727216
TI  - University of Medicine and Dentistry of New Jersey-New Jersey Dental School Oral
      and Maxillofacial Surgery Residency Training Program.

PMID- 18727217
TI  - Is it safe for patients on warfarin to have invasive dental procedures?

PMID- 18727218
TI  - Anatomy of observation: from the Academie Royale de la Chirurgie to the salons of
      Denis Diderot.

PMID- 18727219
TI  - Some connections among the heroes.

PMID- 18727220
TI  - From Nollet to Volta: Lavoisier and electricity.

PMID- 18727221
TI  - Garden of the empire: Catherine's appropriation of the Crimea.

PMID- 18727222
TI  - [Popular festival or state ceremony? The ritual of public execution according to
      two Parisian bourgeois, 1718-89].

PMID- 18727223
TI  - The balancing act of the naked cell: a brief history of membrane regulation of
      animal cell volume before 1978.

PMID- 18727224
TI  - Twenty-five years of K-Cl cotransport: from stimulation by a thiol reaction to
      cloning of the full-length KCCs.

PMID- 18727225
TI  - Molecular physiology of mammalian K(+)-Cl- cotransporters.

PMID- 18727226
TI  - STE20 kinases and cation-chloride cotransporters.

PMID- 18727227
TI  - Molecular physiology of the renal Na(+)-Cl- and Na(+)-K(+)-2Cl- cotransporters.

PMID- 18727228
TI  - The role of the blood-brain barrier Na-K-2Cl cotransporter in stroke.
AB  - Studies from this and other laboratories have shown that the Na-K-2Cl
      cotransporter is present in BBB endothelial cells is stimulated by factors
      present during cerebral ischemia. Further, our in situ studies have shown that
      the cotransporter resides predominantly in the luminal BBB membrane. This is
      consistent with the hypothesis that a luminal cotransporter works with abluminal
      Na/K ATPase to secrete NaCl into the brain, and during stroke, BBB cotransporter
      activity is increased such that the barrier hypersecretes NaCl and water into the
      brain, facilitating cytotoxic edema formation. Our in vivo MCAO stroke studies
      provide further support for a role of the BBB cotransporter in cerebral ede-ma
      formation. Collectively, these findings suggest that the BBB Na-K-2Cl
      cotransporter does indeed substantially contribute to cerebral edema formation in
      stroke.

PMID- 18727229
TI  - Regulation of Na-K-2Cl cotransport in red cells.

PMID- 18727230
TI  - A novel NHE1 from red blood cells of the winter flounder: regulation by multiple
      signaling pathways.

PMID- 18727231
TI  - Probing of the ICln channel pore by cysteine mutagenesis and cadmium-block.

PMID- 18727232
TI  - Volume-dependent and -independent activated anion conductances and their
      interaction in the renal inner medullary collecting duct (IMCD).

PMID- 18727233
TI  - Secretory control of basolateral membrane potassium and chloride channels in
      colonic crypt cells.

PMID- 18727234
TI  - Effects of ammonium on ion channels and transporters in colonic secretory cells.
AB  - Basolateral ammonium produces an inhibition of Cl- secretion the magnitude of
      which is dependent on the NH4+ to K+ concentration ratio. Inhibition is maximal
      at a mole fraction ratio of 0.25 K+ to NH4+. This anomalous mole fraction effect
      is due to effects on the basolateral K+ channel as well as Na(+)-K(+)-2Cl-
      cotransporter. However, only Cl- loading, not K+ loading, appears affected in an
      anomalous mole fraction manner. Transepithelial current is only slightly
      inhibited relative to equilmolar K+ by NH4+. As in other systems, both Na(+)-K(+)
      ATPase and Na(+)-K(+)-2Cl- can act in Na(+)-NH4(+)-ATPase and Na(+)-NH4(+)-2Cl-
      transport modes. NH4+ conducts through most K+ channels and thus likely through
      the apical K+ channel present in native crypt cells. This suggests that, similar
      to the kidney, colonic secretory cells have the capacity to secrete NH4+ when in
      a K(+)-secreting mode with elevated basolateral NH4+ levels.

PMID- 18727235
TI  - The volume-activated chloride current depends on phospholipase C activation and
      intracellular calcium mobilization.

PMID- 18727236
TI  - Nitric oxide (NO) modulation of Cl-dependent transporters in the kidney.

PMID- 18727237
TI  - Volume activated anion channel and astrocytic cellular edema in traumatic brain
      injury and stroke.

PMID- 18727238
TI  - Effectors and signaling events activated by cell shrinkage in ehrlich ascites
      tumor cells: implications for cell proliferation and programmed cell death.

PMID- 18727239
TI  - Water movement during apoptosis: a role for aquaporins in the apoptotic volume
      decrease (AVD).

PMID- 18727240
TI  - Apoptosis and cell volume regulation: the importance of ions and ion channels.

PMID- 18727241
TI  - Anion channel involved in induction of apoptosis and necrosis.

PMID- 18727242
TI  - Erythrocyte ion channels in regulation of apoptosis.
AB  - Erythrocytes lack mitochondria and nuclei, key organelles in the regulation of
      apoptosis. Until recently, erythrocytes were thus not considered subject to this
      type of cell death. However, exposure of erythrocytes to the Ca2+ ionophore
      ionomycin was shown to induce cell shrinkage, cell membrane blebbing and
      breakdown of phosphatidylserine asymmetry with subsequent phosphatidylserine
      exposure at the cell surface, all typical features of apoptosis. Further studies
      revealed the participation of ion channels in the regulation of erythrocyte
      "apoptosis." Osmotic shock, oxidative stress and energy depletion all activate a
      Ca2(+)-permeable non-selective cation channel in the erythrocyte cell membrane.
      The subsequent increase of Ca2+ concentration stimulates a scramblase leading to
      breakdown of cell membrane phosphatidylserine asymmetry and activates Ca2+
      sensitive K+ (Gardos) channels leading to KCl loss and (further) cell shrinkage.
      Phosphatidylserine exposure and cell shrinkage are blunted in the nominal absence
      of extracellular Ca2+, in the presence of the cation channel inhibitors amiloride
      or ethylisopropylamiloride, at increased extracellular K+ or in the presence of
      the Gardos channel inhibitors clotrimazole or charybdotoxin. Thus, increase of
      cytosolic Ca2+ and cellular loss of K+ participate in the triggering of
      erythrocyte scramblase. Nevertheless, phosphatidylserine exposure is not
      completely abrogated in the nominal absence of Ca2+, pointing to additional
      Ca2(+)-independent pathways. One of those is activation of sphingomyelinase with
      subsequent formation of ceramide which in turn leads to stimulation of
      erythrocyte scramblase. The exposure of phosphatidylserine at the extracellular
      face of the cell membrane stimulates phagocytes to engulf the apoptotic
      erythrocytes. Thus, sustained activation of the cation channels eventually leads
      to clearance of affected erythrocytes from peripheral blood. Erythropoietin
      inhibits the non-selective cation channel and thus interferes with erythrocyte
      "apoptosis." Susceptibility to scramblase activation is enhanced in thalassemia,
      sickle cell disease and glucose-6-phosphate dehydrogenase deficiency. Infection
      with Plasmodium falciparum leads to activation of the cation channel eventually
      triggering erythrocyte "apoptosis."

PMID- 18727243
TI  - Apoptosis vs. oncosis: role of cell volume and intracellular monovalent cations.
AB  - Several research teams have proposed that shrinkage and swelling in cells
      undergoing apoptosis and oncosis are not only the earliest morphological markers
      of the two modes of cell death but are also obligatory steps in the development
      of the death machinery. We examined this hypothesis as well as the role of
      monovalent cations as major intracellular osmolytes using vascular smooth muscle
      cells (VSMC) from the rat aorta and C7-MDCK cells derived from the Madin-Darby
      canine kidney. 48-hr inhibition of the Na(+)-K+ pump with ouabain did not affect
      VSMC survival and delayed serum deprivation-induced apoptosis at a step upstream
      of caspase-3 via elevation of the [Na+]i/[K+]i ratio and the expression of Na+ i
      sensitive antiapoptotic genes including mortalin. Transient and modest (15-20%)
      shrinkage observed in serum-deprived VSMC did not contribute to triggering of the
      apoptotic machinery. In contrast to VSMC, ouabain led to oncosis of C7-MDCK
      cells, indicated by swelling and resistance to the pan-caspase inhibitor z
      VAD.fmk. In these cells, the death signal was mediated by interaction of ouabain
      with the Na(+)-K(+)-ATPase alpha-subunit but was independent of the inhibition of
      Na(+)-K+ pump-mediated ion fluxes and elevation of the [Na+]i/[K+]i ratio.

PMID- 18727244
TI  - Polycystin-2 as a signal transducer.

PMID- 18727245
TI  - Further characterization of the nematode IClnN2 protein reconstituted in lipid
      bilayers.

PMID- 18727246
TI  - Hypertonicity-induced cation channels in rat hepatocytes and their intracellular
      regulation.

PMID- 18727247
TI  - Cell volume sensing and regulation in skeletal muscle cells: lessons from an
      invertebrate.

PMID- 18727248
TI  - Q-VD-OPh, next generation caspase inhibitor.

PMID- 18727249
TI  - Are membrane tyrosine kinase receptors involved in osmotransduction?

PMID- 18727250
TI  - Glial-neuronal signaling and astroglial swelling in physiology and pathology.

PMID- 18727251
TI  - Cell swelling-induced peptide hormone secretion.
AB  - Cell volume changes induced in various ways (anisosmotic environment, hormones,
      oxidative stress, substrate uptake) are an integral part of a signal transduction
      network regulating cell function. Cell swelling has received increasing attention
      as a stimulus for a variety of intracellular phenomena. One of the most
      remarkable effects of cell swelling is its powerful effect in inducing exocytosis
      of material in intracellular secretory vesicles. Secretion of essentially all so
      packaged hormones including those from hypothalamus (thyrotropin-releasing
      hormone, TRH; gonadotropin-releasing hormone, GnRH), pituitary (LH, FSH, ACTH,
      MSH, TSH, prolactin, beta endorphin), pancreas (insulin, somatostatin, glucagon),
      heart (atrial natriuretic hormone) and kidney (renin) are stimulated in a
      concentration-related manner by medium hyposmolarity or isosmolar medium
      containing permeant molecules such as ethanol or urea (reviewed in Ref. 21). Cell
      swelling-induced exocytosis is not restricted to endocrine cells and hormones;
      medium hyposmolarity also induces secretion of exocrine pancreatic enzymes and
      myeloperoxidase from human polymorphonuclear leukocytes.

PMID- 18727253
TI  - Cell volume regulation in intestinal epithelial cells.

PMID- 18727252
TI  - Volume regulation of the hippocampus.

PMID- 18727254
TI  - Regulation of epithelial electrolyte transporters through protein-protein
      interactions.

PMID- 18727255
TI  - The role of the phosphoinositide pathway in hormonal regulation of the epithelial
      sodium channel.
AB  - In summary, insulin and aldosterone stimulate phosphatidylinositol
      phosphorylation, thus indicating the existence of a regulated protein at or
      before the PI3-kinase step. Aldosterone induces the synthesis of sgk, a
      downstream element of the PI pathway. Sgk is necessary, but not rate-limiting,
      for aldosterone- and insulin-stimulated Na+ transport. However, the enzyme
      appears to be rate-limiting for the natriferic action of ADH. Insulin-stimulated
      Na+ transport, an acute response, is dependent on PI3-kinase activity but the
      magnitude of the response is not altered by a cellular excess of sgk. ADH
      stimulated transport is not dependent on PI3-kinase but is potentiated by an
      excess of sgk. The foregoing data indicate that the PI pathway is involved in
      several steps of the natriferic action of hormones and intersects with other
      pathways which regulate ENaC. Furthermore, the data are consistent with the
      hypothesis that activation of PI3-kinase may ultimately stimulate channel
      insertion as well as regulate channel endocytosis. Both of these phenomena can
      result in an increase of ENaC-mediated Na+ transport.

PMID- 18727256
TI  - Modulation of volume-sensitive taurine release from NIH3T3 mouse fibroblasts by
      reactive oxygen species.

PMID- 18727257
TI  - Hypertension in K-Cl cotransporter-3 knockout mice.

PMID- 18727260
TI  - The abuse of older people and compulsory reporting.

PMID- 18727259
TI  - Caring for the disadvantaged: a time of opportunity and challenge. Interview by
      Melissa Sweet.

PMID- 18727261
TI  - Working life.

PMID- 18727262
TI  - Abortion law needs change.

PMID- 18727263
TI  - Leaving the paper trail behind.

PMID- 18727264
TI  - Listeria monocytogenes--which of your patients is not at risk?
AB  - Listeria monocytogenes is an environmental bacterium that is capable of causing
      infection (known as listeriosis) in vulnerable people who generally acquire the
      organism following the ingestion of contaminated foods. Pregnant women are a
      particular risk group, as listeriosis in pregnancy is associated with an
      increased risk of spontaneous abortion, stillbirth, neonatal septicaemia and
      meningitis. The immunocompromised, and people over the age of 65 to 70 are also
      at increased risk of listeriosis. Listeriosis can present in a number of ways and
      may lead to significant morbidity. The mortality rate is between 11% and 60%
      depending on the age of the patient and the clinical presentation of the
      infection. There has been wide coverage in both medical and public media of the
      risk of listeriosis in pregnancy, but little has been published in general
      nursing journals. The objective of this article is to raise nurses' awareness of
      listeriosis enabling them to offer optimum advice to vulnerable patients.

PMID- 18727265
TI  - World leading exercise program for renal dialysis patients.

PMID- 18727266
TI  - Adolescent health and diabetes: time to rethink service delivery.

PMID- 18727267
TI  - Time to grow up and let nurses get on with caring for patients.

PMID- 18727268
TI  - Therapeutic approach to hepatocellular carcinoma: a difficult choice.
AB  - In this paper the most important problems regarding diagnosis and treatment of
      HCC will be discussed in detail by the Authors. In an analysis of therapeutic
      options, the methods used over the past decades will be looked at. The conclusion
      is that choices must always be made in a rational manner and with good sense.

PMID- 18727269
TI  - Hepatocellular dysplastic nodules.
AB  - The multistep process of hepatic carcinogenesis is mirrored by the morphologic
      classification of lesions detectable in cirrhosis, that include large
      regenerative nodules (LRN), low grade dysplastic nodules (LGDN) and high grade
      dysplastic nodules (HGDN). The latter belong to the "bordeline malignancy"
      cathegory requiring an accurate distinction from well-differentiated and early
      hepatocellular carcinoma. Nodules in cirrhosis are usually detected by non
      invasive imaging techniques, being the latter unable to discriminate malignant
      from non-malignant forms, particularly in the 1-2 cm sized group. Liver biopsy is
      essential in providing practical diagnostic information to hepathologists in the
      management of cirrhotic patients with US detectable nodules. The histologic
      diagnosis on liver samples is based on the accurate search of a set of cyto
      architectural features (cell atypia, cell crowding, trabecular thickness,
      microacini etc) and by a supplement of histochemical (Gomori staining) and
      immunocytochemical stainings. The latter rely upon the search of both well
      established and novel markers, targeted to evaluate stromal invasion (CK7/19),
      the vascular pattern (ASMA and CD34) or tumor markers (HSP70 and Glipican 3 among
      others). Still, the diagnostic sensitivity is limited by the type and size of
      sampling and by its representativity of the entire lesion. The best diagnostic
      approach thus requires the integration of clinical, morphological and
      immunocytochemical information with imaging data (US pattern, perfusional
      pattern, helical CT/MR pattern). Molecular data are still under evaluation as to
      their diagnostic efficacy in this controversial field. Discrepancies have emerged
      recently between Eastern and Western interpretation of these lesions,
      particularly in the cathegory of "borderline" nodules, that are mostly labelled
      as early, well differentiated HCC by eastern pathologists and as HGDN by western
      pathologists. Novel and more objective phenotypical and molecular markers are
      needed to discriminate within the grey area of borderline lesions that,
      epidemiologically, are likely distinct between eastern and western geographic
      areas. These tools might allow a better understanding of the boundaries of the
      process going from high grade dysplasia to in situ HCC and from the latter to
      microinvasive HCC and advanced HCC, for a proper clinical management and optimal
      therapy.

PMID- 18727271
TI  - Intraoperative ultrasound in surgery for hepatocellular carcinoma.
AB  - Imaging-guided therapeutic procedures have modified the approach to HCC both
      introducing new treatment modalities and also changing the policy of
      hepatectomies. Indeed, with intraoperative ultrasonography (IOUS) it is possible
      to achieve better knowledge about tumor location and staging, also with the aid
      of contrast-enhanced IOUS. However, IOUS also allows to minimise the rate of
      major hepatectomies maintaining treatment radicality and widening the indication
      at surgery. Indeed, precise definition of tumor-vessel relationship, intrahepatic
      vessel distribution and color-Doppler analysis allows performing hepatectomies
      otherwise not possible. This so-called "radical but conservative" policy has
      allowed us a safe surgical approach with minimal mortality and major morbidity
      and effective local treatment with no tumor relapses at the site of the
      resection. Techniques for safe and radical IOUS-guided liver resections for HCC
      are here discussed.

PMID- 18727270
TI  - Natural history of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a slowly growing tumor, whose natural history
      is not completely known. Since the hepatocarcinogenetic process may evolve for
      years in a stepwise fashion from premalignant to overt HCC, detection of early,
      better treatable tumors is made possible by surveillance of patients at risk. A 6
      month interval surveillance with ultrasound is considered cost-effective,
      generally leading to the identification of a single < 3 cm tumor in 50-70% of the
      patients at risk. For greater than 2 cm tumors, demonstration of arterial
      hypervascularization of the node by sonovue US, triphasic spiral CT or MRI is
      diagnostic for HCC. The diagnosis of a less than 2 cm in diameter tumor may be
      more difficult due to the risk of false negative diagnoses with contrast imaging
      technique (50% of the cases) caused by immature arterial vascularization of the
      small nodules. Prognosis largely depends on the evolutionary stage at which HCC
      is detected, i.e. a size and number of HCC nodes, vascular invasiveness and
      degree of liver impairment. The multinodular pattern of HCC, representing one
      third of all early cancers, heralds poor prognosis, especially for patients not
      fitting the Milan criteria for liver transplantation. The best prognosis is for a
      single, less than 5 cm node in compensated cirrhosis without vascular invasion,
      since this tumor is amenable to both liver transplantation and hepatic resection
      which may confer long-term survival Better survivals of cirrhotic patients with a
      recently identified tumors reflect the application of accurate criteria for tumor
      staging and stringent criteria for curative treatments. However, ageing of the
      patients, deterioration of liver function during surveillance, occurrence of
      multinodular tumors and limited access to liver transplantation may hamper
      surveillance programs effectiveness.

PMID- 18727272
TI  - Conformal and stereotactic radiotherapy in hepatocellular carcinoma.
AB  - Historically, Radiation Therapy (RT) has played a minor role in the treatment of
      hepatocellular carcinoma, especially because of toxicity related to conventional
      techniques. However, high radiation doses can now be given safely by means of 3D
      conformal techniques and other more specialized techniques. 3D-conformal RT, in
      which both target definition and treatment planning are based on three
      dimensional image data sets, provided good local control in several series. As an
      evolution of cranial radiosurgery, stereotactic body radiation therapy (SBRT) is
      currently being employed as a new tool for the treatment of HCC, as it offers the
      opportunity of achieving radioablation for tumors up to 6 cm in diameter with a
      minimal risk of radiation induced liver disease. SBRT is distinguished by the
      fact that both planning and treatment are guided by reference to a system of
      external stereotactic coordinates. As a consequence, SBRT may succeed in
      minimizing geometric treatment uncertainties, thus allowing the delivery of high
      doses to the target, given in a small number of fractions. In several published
      series of SBRT for HCC, actuarial 5-year local control rates higher than 80% have
      been achieved In short, radiation therapy should be considered as a useful
      addition to the treatment spectrum of HCC.

PMID- 18727273
TI  - Hepatic resection for hepatocellular carcinoma in cirrhosis.
AB  - Hepatocellular carcinoma is one of the most common cancers worldwide. Several
      treatment modalities have been proposed, but hepatic resection is still
      considered the first-line therapeutic option for most of the patient carries of
      HCC. The proper selection of patients candidate to hepatic resection for HCC and
      the eradication whenever is possible of the intrahepatic metastases are the most
      crucial steps for improving the surgical outcome in HCC. This article reviews the
      current state of the art of the surgical treatment of HCC.

PMID- 18727274
TI  - Bilateral breast cancer in a male patient with hepatocellular carcinoma. A case
      report.
AB  - Male breast cancer accounts for about 1% of all breast cancers and bilateral
      breast cancer in men is therefore a rare event. Data in literature indicate that
      approximately 20% of these tumours are due to a probable alteration in the
      oestrogen metabolism. Hepatocellular carcinoma (HCC) on the other hand, is a much
      more frequent tumour and in 70-80% of cases is associated with cirrhosis. The
      proven concomitance of cirrhosis and gynecomastia in HCC or previous intake of
      oestrogen in breast cancer, would indicate possible involvement of the hormonal
      metabolism in the appearance of the two neoplastic forms. To our knowledge a case
      with these two malignant diseases in the same male patient is an exceptional
      event, rarely reported in literature. The fact that the breast cancer was
      bilateral in a male patient, the diverse histogenesis of the two breast cancers
      and the association with HCC in cirrhosis, led us to investigate into any common
      eziopathogenetic elements.

PMID- 18727275
TI  - [Surgical treatment of primary hyperparathyroidism: our experience].
AB  - The Authors report their experience on 136 patients with primary
      hyperparathyroidism. Nephrolitiasis was proven in 56 patients (41.3%), 20
      patients (14.7%) were asyntomatic. Acute primary hyperparathyroidism was detected
      in 12 cases (8.8%). The preoperative localization of the diseased glands permits
      to minimize the procedure in terms of length and region of incision, extent of
      exploration and morbidity. 91.3% of the lesions were single adenoma, 7.3% double
      adenomas and 1.4% hyperplasia in MEN 1. The intraoperative PTH assay, performed
      in 90 patients (66.2%), showed a sensibility of 93.4%. Surgical treatment was
      successful in 93.4% of cases ( 127/136 patients), increasing to 97.0%
      (132/136patients) if only recurrent hyperparathyroidism was considered, with no
      mortality and morbidity of 4.4%.

PMID- 18727276
TI  - [Treatment of splenic trauma in paediatric age].
AB  - The splenic trauma in children presents some peculiarity that differentiates it
      from that one in adult age. Therefore we have see again our relative experience
      on splenic trauma, in the period 2001-2006, confronting two groups of patients,
      one of inferior age to fourteen years (A Group) and one of advanced age (B
      Group). We have estimated the following parameters: aetiology, type of lesion,
      association with others trauma, type of treatment, compliance, mortality, number
      of transfusions and hospital stay. On a total of 75 splenic trauma (M:52, F:23 of
      age comprised between 5 and 71 years) 18 belongs to the A group (medium age of
      9.2 years) and 57 to the B group (medium ages of 47.4 years). The prevailing
      aetiology in the A group is domestic accident (39%) and the fall from bicycle
      (33%), while in the B group it is the street accident (69%). The lesions found in
      pediatric age are of smaller gravity if compared with B group, for lesion gravity
      and for association with abdominal and/or extra-abdominal others trauma. In the
      children group we have performed nonoperative management or conservative surgery
      in the 83% of cases versus the 26% in the B group. The rate of conversion from a
      nonoperative treatment in to an operative treatment has been of 7%. The post
      operative complicance are absent in the A group and of 5.5% in the B group. The
      mortality rate in the surgical patients has been of the 14.3% for serious toraco
      abdominal trauma in A group and of 11.1% in B group. No mortality is detected in
      the groups with nonoperative treatment. The medium number of transfusions is of
      1.8 units in the paediatric patients and of 2.5 units in the adults. The medium
      stay in hospital is of eighteen days in the A group and of thirteen days in the B
      group. In conclusion the marked difference in the two groups examines stays in
      the type of treatment, more often nonoperative or conservative in the children
      group.

PMID- 18727277
TI  - Clinical evaluation of epithelioid angiomyolipoma.
AB  - OBJECTIVE: Epithelioid angiomyolipomas (AML) of the kidney are malignant tumors
      with aggressive clinical behavior. METHODS: The Authors report on some cases
      epithelioid AM recently diagnosed at their Institute to highlight the spectrum of
      clinical presentations. RESULTS: In all cases, renal lesions observed at computed
      tomography were suspicious for renal cell carcinoma (RCC). Histologically, these
      tumors can resemble RCC. The diagnosis of epithelioid AML was established by
      positive staining for melanoma and smooth muscle cell markers, and presence of
      perivascular epithelioid cells. Four patient presented with a renal tumor
      extending into the inferior vena cava to the level of the hepatic veins. Two
      patients developed recurrent, metastatic disease following nephrectomy.
      CONCLUSIONS: These tumors are distinguished from RCC by positive immunostaining
      for melanoma markers and smooth muscle cell markers. They resemble conventional
      RCC on imaging. Epithelioid AML, may be locally aggressive and metastasized.

PMID- 18727278
TI  - Brunner's gland hamartoma: a case report and review of literature.
AB  - BACKGROUND: Brunner's hamartoma is a quite rare neoformation whose origin is not
      completely clear. METHODS: A case of a 69-year-old man with recurrent epigastric
      pain and an endoscopic finding of a duodenal mass is reported. RESULTS: The
      complete removal of hamartoma can give a complete remission of symptoms.
      CONCLUSIONS: Hamartoma can be only diagnosed by endoscopy and histological exam;
      its therapy is always surgical, also in order to avoid possible malignant
      degeneration.

PMID- 18727279
TI  - Effects of nimodipine administration on small bowel mucosa under conditions of
      laparotomy and consequent 48-hour starvation in a rat model.
AB  - BACKGROUND/AIMS: The combination of starvation and surgical trauma induces
      disturbances to the intestinal mucosal structure and function, as well as changes
      in mucosal barrier function in the rat small bowel. The aim of the present study
      was to evaluate the effects of nimodipine administration, on intestinal mucosal
      structural changes and enterocyte apoptosis, following laparotomy and subsequent
      postsurgical starvation (PSS) in the rat. METHODS: Thirty Wistar rats were
      divided into two experimental groups: A: Control group (n=15), where the animal
      models underwent laparotomy and consequent 48-hours PSS and B: Nimodipine group
      (n=15), where the rats underwent laparotomy, followed by intraperitoneal
      nimodipine administration and consequent 48-hour (h) PSS. Small bowel mucosal
      structural changes and enterocyte epithelial apoptosis were determined 48 h
      following laparotomy. RESULTS: Nimodipine rats (group B) demonstrated a
      significant decrease in small bowel villous height in jejunum (p=0.016) and ileum
      (p=0.002). Similarly, crypt depth decreased in jejunum (p<0.001) and ileum
      (p<0.001). Nimodipine group exhibited significantly higher apoptotic index in
      ileum compared to control rats (p=0.006). CONCLUSION: Nimodipine did not protect
      the intestinal mucosa from damage caused by surgery and consequent PSS and had
      obvious damaging effects on intestinal mucosa with derangements to its structure
      and subsequent mucosal atrophy.

PMID- 18727280
TI  - CCCN's 35th anniversary.

PMID- 18727281
TI  - Chronic kidney disease in the context of cardiovascular disease: a brief
      overview.

PMID- 18727282
TI  - Prevalence of cardiovascular risk factors in grade nine students.
AB  - BACKGROUND: The Niagara Schools' Healthy Heart Program (NSHHP) is a health
      education and intervention program offered to students enrolled in a grade nine
      physical education course. The program involves completion of a family history
      and a self-report lifestyle survey, measurements of height, weight, blood
      pressure, and random total cholesterol levels, a heart education class, and CPR
      training. PURPOSE: The purpose of this study was to report the prevalence of
      cardiovascular risk for adolescents enrolled in the program. METHODS: A secondary
      analysis was conducted using data collected by the NSHHP staff to determine the
      prevalence of cardiovascular risk factors in grade nine students for the school
      year 2006. Specific risk factors studied were smoking, body mass index, total
      cholesterol level and blood pressure. RESULTS: A total of 3,639 students from 30
      schools participated. Almost 14% of students had at least one cardiovascular risk
      factor. Body mass index was found to be the highest risk factor (13.7%) and total
      random cholesterol level (5%) was found to be the lowest risk factor in this
      sample. There were differences in prevalence rates between male and female
      students for all risk factors except elevated blood pressure. Five per cent of
      the students were referred to a family physician for follow-up, mostly for high
      cholesterol readings. CONCLUSIONS: The findings suggest that adolescents do have
      cardiovascular risk factors and prevention could be targeted to this population.
      These risk factors were already established by the time the students reached
      adolescence. The findings support conducting early prevention with younger
      children and adolescents.

PMID- 18727283
TI  - Women's experiences of cardiac pain: a review of the literature.
AB  - BACKGROUND: Women experience coronary heart disease (CHD) differently than men.
      Presentations of cardiac pain for women can include vague signs and symptoms such
      as extreme fatigue, discomfort in the shoulder blades, and shortness of breath.
      Subsequently, the assessment, identification, treatment, and rehabilitation of
      women with CHD present challenging and unique opportunities for nurses because
      women experience a multiplicity of symptoms that are often not reported or
      recognized as cardiac in nature. Women have higher rates of functional disability
      and a lower prevalence of obstructive coronary heart disease, as evidenced by
      coronary angiogram, than men. It is important to understand the complexities of
      women's presentations of cardiac pain if nurses are to improve the quality of
      health experienced post diagnosis, treatment, and rehabilitation. PURPOSE: The
      purpose of this article is to identify current qualitative studies that
      specifically explore women's experiences of cardiac pain and to describe salient
      themes across the literature identifying implications for clinical practice and
      areas of further research related to women's cardiac pain experience. METHOD:
      Qualitative studies that were published in nursing literature between the years
      of 1995 and 2007 were analyzed to illustrate the current state of qualitative
      research on women's cardiac pain experiences. This review includes six articles
      that met the inclusion criteria. CONCLUSION: Results of this review revealed that
      women experience cardiac pain differently than men. Different cardiac pain
      experienced by women leads to misunderstandings of warning signs and symptoms of
      myocardial infarction and ischemic cardiac pain. Moreover, women do not recognize
      the threat of CHD, even with significant family history, and delay seeking health
      care for signs of acute myocardial infarction. Further research and education are
      warranted. Nurses need to challenge the antiquated assumptions surrounding
      women's experiences of cardiac pain. Clinicians must be cognizant of the
      importance of a thorough patient assessment, the ability to identify women at
      risk, individualizing the person's CHD experience, and providing health promotion
      strategies that educate women to recognize the signs and symptoms of CHD. Studies
      that identify the educational needs specific to women and cardiac pain are
      necessary. Educational intervention studies promoting health-related behaviour
      change that targets cardiac pain recognition for women are imperative. Future
      research examining whether the experience of changes in cardiac pain over time
      and post-intervention(s) need to be conducted.

PMID- 18727284
TI  - Evidence-based cardiovascular nursing practice: Why? For whom? Where and how?

PMID- 18727285
TI  - [Controversy and a constructive attitude].

PMID- 18727286
TI  - [Awareness and dealing with structure].

PMID- 18727287
TI  - [Non-discriminatory attitudes in nurses require "cultural competence"].

PMID- 18727288
TI  - [How can nurses become more efficient and cheaper?].

PMID- 18727289
TI  - [Interacting with agitated behaviors].

PMID- 18727290
TI  - [Struggling with self-understanding in professional recruitment].

PMID- 18727291
TI  - [Management of efflux begins before influx].

PMID- 18727292
TI  - [A service (not only) for women].

PMID- 18727293
TI  - ["Good pain management should have the label of quality care"].

PMID- 18727294
TI  - [Personality serves to lessen anxiety].

PMID- 18727295
TI  - [Respect, above all else].

PMID- 18727296
TI  - [From charity to "durable humanitarian action"].

PMID- 18727297
TI  - [Human relations, source of life and healing].

PMID- 18727298
TI  - [A case of close relations and intelligence].

PMID- 18727300
TI  - [The path of the future in question].

PMID- 18727299
TI  - [You said "pleasure"?].

PMID- 18727301
TI  - [Launching the evidence: the priority of Alzheimer disease].

PMID- 18727302
TI  - [Skin deep].

PMID- 18727303
TI  - Health savings accounts: who really benefits?

PMID- 18727304
TI  - Alleviating patient refunds doesn't have to be painful.

PMID- 18727305
TI  - Collecting at time of service.

PMID- 18727306
TI  - HAI prevention emphasized in 2009 National Patient Safety Goals.
AB  - * Having an infection control program already in place does no ensure compliance
      with new NPSGs. * Patient involvement, education are critical components in
      preventing HAIs. * New requirements mean more levels of documentation.

PMID- 18727307
TI  - Joint Commission issues staff behavior standard.
AB  - * Medical literature provides evidence that inappropriate behaviors can cause
      adverse outcomes. * The Joint Commission wants code of conduct, with consequences
      for bad behaviors. * Quality managers should emphasize a pattern of behavior
      rather than an isolated incident.

PMID- 18727308
TI  - Heparin overdose scare in 14 babies at Texas hospital.
AB  - * Properly dosing meds for pediatric patients involves unique challenges. * All
      children for whom medication is being prescribed should be weighed in kilograms.
      * Be sure to test out your CPOE system thoroughly before starting implementation.

PMID- 18727309
TI  - Reduce ED violence with training, diligent reporting.
AB  - * Encourage careful reporting of all violent incidents. * Provide training in how
      to recognize and respond to potential violence. * Do not hesitate to call local
      law enforcement for help.

PMID- 18727310
TI  - You'll need this data on patient QI involvement.
AB  - * Patients should be included in hospital committees and advisory boards. *
      Including patients in quality improvement is a new trend in health care. *
      Outcomes data should be collected to determine the impact of patients'
      involvement.

PMID- 18727311
TI  - Use proven strategies for error disclosure to patients.
AB  - * Workforce needs to be prepared and to deliver effective error disclosure. * At
      Baylor, quality, safety, and risk management are involved in error disclosure. *
      Quality professionals should get to the bottom of the problem.

PMID- 18727312
TI  - The effect for oncology of the national coverage determination for erythropoiesis
      stimulating agents.

PMID- 18727313
TI  - Improving outcomes in cardiovascular disease.

PMID- 18727315
TI  - A conversation with James K. Min, MD.

PMID- 18727314
TI  - Acute coronary syndromes.
AB  - The mortality rate for coronary artery disease has decreased steadily over the
      past 25 yeas, attributable to a great extent to advances in medical and
      mechanical interventions. Nevertheless, mortality rates for acute coronary
      syndromes remain between 4% and 7%. This article highlights treatment options and
      the challenge of implementing evidence-based recommendations.

PMID- 18727316
TI  - Heart disease and managed care.
AB  - Although the use of beta blockers has measurably improved the state of cardiac
      care in the United States, more work remains to be done. Other meritorious
      interventions for cardiovascular conditions that deserve attention by MCO's.
      Given the continuing clinical and and cost burden of heart disease, MCO's can use
      the lessons learned from the success of beta blockers in other important areas of
      cardiovascular care, including longer-term beta-blocker therapy, treatment of
      lipid disorders, and use of aspirin and thienopyridine derivatives.

PMID- 18727317
TI  - Changes in hospital readmissions for diabetes-related conditions. Differences by
      payer.

PMID- 18727318
TI  - Was Erb's Palsy caused by nurse? New trial ordered.

PMID- 18727319
TI  - 'Simian creases' prove 'prenatal' injury: no liability. Case on point: Day v.
      Zuschke, (01/03/2008) P.3d -AZ.

PMID- 18727320
TI  - OH: Failure to have physician expert's affidavit: wrongful death and survivorship
      suit dismissed.

PMID- 18727321
TI  - Nurse practitoner not insured under dr.-employer's policy. Case on point:
      Connecticut Med. Ins. Co. v. Kulikowski, (03/18/2008) A.2d -CT.

PMID- 18727322
TI  - Moving toward COP 15.

PMID- 18727323
TI  - Modelling waste generation by the telecom sector in Nigeria: the grey side of the
      impressive outing.
AB  - Since the introduction of digital mobile technology into Nigeria in 2001, there
      has been a phenomenal improvement in mobile subscription, service delivery and in
      the overall penetration of mobile telecommunication into rural areas in the
      country. For instance, the country's teledensity increased from less than 1% in
      2001 to about 25% in 2006 - an increase of more than 3000%. The aim of this paper
      is to predict improvements in telephone penetration and waste generation by the
      Nigerian telecommunications sector. This was achieved by regression analysis of
      available data on telephone subscription in the country. Our estimations indicate
      that an average of 3 million phones will be retired annually in the country.
      Considering an economic phone life of 4 years, the over 32 million phones,
      (weight estimated at about 3200 tons) in use in 2006 would be at their end-of
      life (EoL) by 2010. This volume of waste may contain up to 1800 tons of waste
      plastics, 15 tons of lead and 124 tons of copper. Our derived regression equation
      also indicates that mobile phone penetration in the country would be about 40% by
      2010. This implies that over 55 million mobile phones would be in use by 2010.
      The grey side of this impressive statistics is that waste generation by the
      telecommunications sector will also follow this trend. This paper also highlights
      the need to introduce a framework for the effective management of waste from this
      sector considering the toxicity of some of the components of mobile phones and
      accessories and the prevailing inappropriate disposal practices for such
      potentially 'toxic' materials.

PMID- 18727324
TI  - The performance of Spanish solid waste collection.
AB  - In this paper we examine street cleaning and waste collection services in Spanish
      municipalities with a population exceeding 50,000. The purpose is to identify
      factors that influence the efficiency of these services. Three input variables
      (staff, vehicles and containers) and four outputs variables (tonnage, collection
      points, collection point density and kilometres of surface area washing) are
      analyzed using an analytical model based on Data Envelopment Analysis (DEA)
      methodology. These variables, along with non-controllable input variable (Tourist
      Index), were chosen because they were shown, based on a Tobit regression
      analysis, to have a statistically significant impact on municipality behaviour.
      The results obtained show that scale inefficiency was lower than pure technical
      efficiency, the latter is linked to service management. It was observed that the
      street-cleaning activity was performed more inefficiently than that of waste
      collection. Furthermore, it was detected that municipalities can reduce the
      resources used in rendering this service by 8%. Finally, an estimation using the
      Mann-Whitney test allows us to conclude that there is no difference between the
      inefficiencies observed in municipalities managed directly by town councils and
      those which have been transferred to private companies.

PMID- 18727325
TI  - GIS-based modelling for the estimation of municipal solid waste generation and
      collection.
AB  - In the present paper, an innovative model for the estimation of municipal solid
      waste generation and collection is proposed. This model is part of an extended
      solid waste management system and uses a spatial Geodatabase, integrated in a GIS
      environment. It takes into consideration several parameters of waste generation,
      such as population density, commercial activities, road characteristics and their
      influence on the location and allocation of waste bins. Ground-based analysis was
      applied for the estimation of the inter-relations between the aforementioned
      factors and the variations in waste generation between residential and commercial
      areas. Therefore, the proposed model follows a unified categorization approach
      for residential and commercial activities and focuses on the dominant factors
      that determine waste generation in the area under study. The most important
      result of the research work presented in the current paper is an accurate
      estimation of the optimal number of waste bins and their allocation. A new
      methodology and an appropriate algorithm have been developed for this purpose in
      order to facilitate routing and waste collection. By using these results,
      municipalities aware of social, economical and environmental factors, related to
      waste management, can achieve optimal usage of their resources and offer the best
      possible services to their citizens.

PMID- 18727326
TI  - Nutrients and heavy metals distribution in thermally treated pig manure.
AB  - Ash from pig manure treated by combustion and thermal gasification was
      characterized and compared in terms of nutrient, i.e., potassium (K), phosphorus
      (P) and heavy metal, i.e., cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni)
      and zinc (Zn) contents. Total nutrient and metal concentrations were measured
      using energy dispersive X-ray fluorescence analysis. Acid (HNO3, H2SO4) and water
      extractable concentrations were also measured both in non-classified ash and in
      selected ash particle size fractions using flame atomic absorption spectrometry
      and colorimetric spectrometry. Results indicate that ash from gasified manure
      contained more water-extractable K in comparison with combusted manure whereas
      the opposite was the case with respect to P. Heavy metals Ni, Cr and Cd were
      present in higher concentrations in the fine particle size fractions (< 30 microm
      of particle diameter), whereas K, P, Zn and Cu exhibited higher concentrations in
      the coarser particle size fractions (> 30 microm).

PMID- 18727327
TI  - Describing variability of MSW composition data with the log-logistic
      distribution.
AB  - Variations in solid waste composition data are necessary as inputs to solid waste
      planning, yet uncertainty exists regarding which probability distributions might
      be generally valuable to describe the variability. Twenty-two detailed analyses
      of solid waste from British Columbia, Canada, were fitted to distributions using
      the BestFit software. Alternative distributions were ranked based on three
      goodness-of-fit parameters and twelve waste fractions. The log-logistic
      distribution was found to be the most able to fit over the wide range of
      composition types considered. The results were demonstrated to be insensitive to
      the number of waste components or to the choice of a two- or three-parameter
      distribution. Although other distributions were able to better match the waste
      composition for individual waste types, the log-logistic distribution was
      demonstrated to fit, overall, a wide variety of waste composition types.

PMID- 18727328
TI  - Utilization of kaolin processing waste for the production of porous ceramic
      bodies.
AB  - The kaolin processing industry generates large amounts of waste in producing
      countries such as Brazil. The aim of this study was to characterize kaolin
      processing waste and evaluate its suitability as an alternative ceramic raw
      material for the production of porous technical ceramic bodies. The waste
      material was physically and chemically characterized and its thermal behaviour is
      described. Several formulations were prepared and sintered at different
      temperatures. The sintered samples were characterized to determine their
      porosity, water absorption, firing shrinkage and mechanical strength. Fired
      samples were microstructurally analysed by X-ray diffraction and scanning
      electron microscopy. The results indicated that the waste consisted of quartz,
      kaolinite, and mica, and that ceramic formulations containing up to 66% of waste
      can be used for the production of ceramics with porosities higher than 40% and
      strength of about 70 MPa.

PMID- 18727329
TI  - Volatility of heavy metals during incineration of tannery sludge in the presence
      of chlorides and phosphoric acid.
AB  - Knowledge of the behaviour of heavy metals in the combustion process is a most
      important factor in selecting disposal alternatives for waste materials.
      Accordingly, in this work, the vaporization behaviour of highly concentrated
      heavy metals (Pb, Zn, Cu and Cr) in tannery sludge were investigated
      experimentally. The sludge was spiked with various chlorine compounds (i.e. PVC,
      FeCl3, CaCl2 and NaCl) and pre-treated with phosphoric acid in order to evaluate
      the capacity of enhancement and weakening of the volatility of the heavy metals
      contained in tannery sludge. The experimental results show that the vaporization
      percentages increased with increasing ratio of Cl/sludge and temperature, and the
      accelerating and increasing effect of the addition of chlorides on the
      vaporization percentage of heavy metals was dependent on the release capacity of
      chlorine radicals. The vaporization percentages of lead and zinc increased by 15
      20%, whereas those of copper and chromium increased by only about 3 and 10% at
      800 degrees C. However, heavy metals were not expected to be completely released
      in the combustion process in spite of the high ratio of Cl/sludge. Alternately,
      heavy metals contained in tannery sludge can be immobilized effectively by pre
      treatment with phosphoric acid. When the 85% phosphoric acid accounted for 10% of
      dry basis of tannery sludge, the phosphate-treated sludge showed the lowest
      vaporization percentage of about 3-15% with formation of Ca18Cu3(PO4)14,
      Ca9Cr(PO4)7, Ca19Zn2(PO4)14 and PbMgP2O7 in the bottom ash.

PMID- 18727330
TI  - Metal releases from a municipal solid waste incineration air pollution control
      residue mixed with compost.
AB  - The influence of 10 wt.% mature compost was tested on the heavy metal leachate
      emissions from a calcium-rich municipal solid waste incineration air pollution
      control residue (MSWI APC). Apart from elongated columns (500 and 1250 mm), an
      otherwise norm compliant European percolation test setup was used. More than 99%
      of the metals Al, As, Cd, Cr, Cu, Fe and Ni were left in the APC residue after
      leaching to a liquid-to-solid ratio (L/S) of 10. Apparent short-term effects of
      elevated leachate DOC concentrations on heavy metal releases were not detected.
      Zn and Pb leachate concentrations were one order of magnitude lower for L/S 5 and
      10 from the pure APC residue column, which suggests a possible long-term effect
      of compost on the release of these elements. Prolonging the contact time between
      the pore water and the material resulted in elevated leachate concentrations at
      L/S 0.1 to L/S 1 by a factor of 2. Only Cr and Pb concentrations were at their
      maxima in the first leachates at L/S 0.1. Equilibrium speciation modelling with
      the PHREEQC code suggested portlandite (Ca(OH)2) to control Ca solubility and pH.

PMID- 18727331
TI  - Chemical sequential extraction of heavy metals and sulphur in bottom ash and in
      fly ash from a pulp and paper mill complex.
AB  - A five-stage sequential extraction procedure was used to determine the
      distribution of 11 metals (Cd, Cr, Cu, Mo, Pb, Zn, As, Co, V, Ni, Ba), and
      sulphur (S) in bottom ash and in fly ash from a fluidized bed co-combustion (i.e.
      wood and peat) boiler of Stora Enso Oyj Oulu Mill at Oulu, Northern Finland, into
      the following fractions: (1) water-soluble fraction (H2O); (2) exchangeable
      fraction (CH3COOH); (3) easily reduced fraction (NH2OH-HCl); (4) oxidizable
      fraction (H2O2 + CH3COONH4); and (5) residual fraction (HF + HNO3 + HCl).
      Although metals were extractable in all fractions, the highest concentrations of
      most of the metals occurred in the residual fraction. From the environmental
      point of view, this fraction is the non-mobile fraction and is potentially the
      least harmful. The Ca concentrations of 29.3 g kg(-1) (dry weight) in bottom ash
      and of 68.5 g kg(-1) (dry weight) in fly ash were correspondingly approximately
      18 and 43 times higher than the average value of 1.6 g kg(-1) (dry weight) in
      arable land in Central Finland. The ashes were strongly alkaline pH
      (approximately 12) and had a liming effects of 9.3% (bottom ash) and 13% (fly
      ash) expressed as Ca equivalents (dry weight). The elevated Ca concentrations
      indicate that the ashes are potential agents for soil remediation and for
      improving soil fertility. The pH and liming effect values indicate that the ashes
      also have a pH buffering capacity. From the environmental point of view, it is
      notable that the heavy metal concentrations in both types of ash were lower than
      the Finnish criteria for ash utilization.

PMID- 18727333
TI  - We are making an impact.

PMID- 18727332
TI  - Effect of drying on leaching testing of treated municipal solid waste
      incineration APC-residues.
AB  - Air-pollution-control (APC) residues from waste incinerators are hazardous waste
      according to European legislation and must be treated prior to landfilling. Batch
      and column leaching data determine which type of landfill can receive the treated
      APC-residues. CEN standards are prescribed for the batch and column leaching
      test; however, these standards do not specify whether or not the residue samples
      should be dried prior to the leaching testing. Laboratory tests were performed in
      parallel (dried/non-dried) on treated APC-residue samples and evaluated with
      respect to Cr, Cd, Cu, Pb and Zn leaching. The effect of drying of the wet APC
      residue samples was particularly dramatic regarding the leaching of Cr. Drying
      resulted in 10-100 times more Cr leaching in both batch and columns test. Drying
      also affected the leaching of Cd, Cu and Pb. Initial Cd leaching was up to 100
      times higher in column tests with dried APC-residue than in tests with wet
      residues. The effect of drying appeared to be a combination of decreasing the
      reduction capacity of the sample (Cr), decreasing pH (Cd, Cu) and in column tests
      also a wash-out of salts (probably affecting Cd and Pb). If the leaching tests
      are intended to mimic landfill conditions, the results of this paper suggest that
      the tests should be done on wet, non-dried residue samples, although this may be
      less practical than testing dried samples.

PMID- 18727334
TI  - Why nursing research?

PMID- 18727335
TI  - Intravascular temperature modulation as an adjunct to secondary brain injury
      prevention in a patient with an epidural hematoma.
AB  - Epidural hematomas (EDHs) account for 10% of fatal injuries in patients with head
      trauma. Up to 35% of patients suffering EDHs develop secondary brain injury
      within days after the initial trauma. Secondary brain injury can profoundly
      affect a patient's subsequent neurologic recovery and functional status. This
      case study presents a patient who developed an EDH following severe head trauma
      with signs and symptoms of secondary brain injury; intravascular temperature
      modulation was used to treat the secondary injury for a prolonged period of 13
      days. The patient showed a complete neurologic recovery with return to work 6
      months after her injury.

PMID- 18727336
TI  - Implementation of the Canadian Neurological Scale on an acute care neuroscience
      unit: a program evaluation.
AB  - The Canadian Neurological Scale (CNS), a validated stroke assessment tool, was
      implemented for the neurological assessment of patients with stroke. The purpose
      of this study was to explore nurses' values and perceptions of best-practice
      guidelines (BPGs) and the CNS assessment, to evaluate the effect of a workshop
      and implementation process on nurses' self-efficacy for CNS use, to determine
      whether the workshop and implementation process met the needs of the nurses, and
      to evaluate the accuracy and appropriateness of CNS assessment documentation.
      Nurses reported moderate-to-strong awareness and use of BPGs and expressed the
      belief that BPGs were valuable; however, they had some difficulty accessing BPGs.
      At 3 months after the workshop, nurses reported using the CNS assessment in
      practice but said that it was not easy to use and that it was not useful as a
      patient status communication tool or for documenting neurological changes. Nurses
      were moderately confident while performing the CNS assessment before the
      workshop. Confidence increased immediately afterward (p < .0001), and then
      decreased slightly at 3 months. The majority of nurses said the workshop met
      their learning needs. A chart audit demonstrated that only 69% of patients
      appropriate for the CNS assessment were assessed with this tool. Although nurses
      are aware of BPGs, translating these changes into practice takes time and may
      require BPG modification to best fit the needs of the areas in which they will be
      used. When choosing a validated stroke assessment tool, clinicians must consider
      how often the tool will be used for assessments, particularly in the acute phase.

PMID- 18727337
TI  - Pushed to the margins and pushing back: a case study of one adult's reflections
      on social interactions after a traumatic brain injury sustained as an adolescent.
AB  - Traumatic brain injury (TBI) is a worldwide chronic health problem. Current
      empirical approaches to defining factors that contribute to a meaningful life
      after TBI have been limited to the biomedical perspective. Such a limited
      paradigm fails to address how people with TBI find meaning and act on and are
      acted on by the world in which they live. Between 2005 and 2007 an in-depth
      qualitative case study was conducted. The primary data source was a man's
      retrospective journal writings about his life after sustaining a severe TBI. The
      qualitative perspective of symbolic interactionism framed this case study
      analysis. Meaning is strongly influenced by the ways in which the social world
      interacts with the injured person. Despite an accumulation of negative social
      experiences, a traumatically brain-injured person can also assign positive
      meanings to the quality of his or her life. This has been ignored or explained
      away as a defense mechanism in previous investigations. More studies that include
      unbiased methods able to capture subjective experiences and what they mean to
      individuals with TBI are needed. This information will lead to more relevant
      interventions and better outcome instruments for use with this population.

PMID- 18727338
TI  - Workplace distress and ethical dilemmas in neuroscience nursing.
AB  - This study concerns Swedish nurses' experiences of workplace stress and the
      occurrence of ethical dilemmas in a neurological setting. Qualitative interviews
      were conducted with 21 nurses. The interview results were subjected to
      qualitative latent content analysis and sorted into 4 content areas: workplace
      distress, ethical dilemmas, managing distress and ethical dilemmas, and quality
      of nursing. Common workplace stressors were high workload and lack of influence.
      These were perceived to have negative consequences for the quality of nursing.
      Ethical dilemmas mainly concerned decision making on initiation or withdrawal of
      treatment, which was experienced as a troublesome situation where conflicts could
      arise. The nurses managed the distress and ethical dilemmas by accepting and
      adjusting to the situation and seeking support from colleagues. They also
      endeavored to gain new strength in their private lives.

PMID- 18727339
TI  - Impact of warm compresses on local injection-site reactions with self
      administered glatiramer acetate.
AB  - Patients with multiple sclerosis (MS) report a number of adverse events related
      to immunomodulator injections, including local injection-site reactions (LISRs).
      Reactions characterized by pain, swelling, redness, or inflammation have been
      experienced by patients who self-inject glatiramer acetate, interferon beta-1b,
      or interferon beta-1a. Although these reactions rarely are serious, they can
      foster negative attitudes about self-injection and undermine a patient's
      commitment to treatment, especially in the early stages of therapy. This
      randomized crossover study of 50 patients who had initiated or restarted
      glatiramer acetate therapy within the 3 months before the study examined whether
      applying a warm compress to the injection site before self-injection would lower
      the incidence of LISRs compared with the patients' usual methods of injection
      preparation. Fewer LISRs were reported both 2 minutes and 5 minutes postinjection
      when warm compresses were used compared with the usual injection-site preparation
      (p < .001). Patients also were less bothered by LISRs when using warm compresses,
      as shown by mean scores on the Bothersome Scale (p = .02). Because warm
      compresses are easy to apply and appear to be at least modestly effective, they
      should be considered when recommending alternatives for patients who experience
      LISRs associated with glatiramer acetate. Warm compresses may be of particular
      benefit for those who have recently begun therapy with glatiramer acetate to help
      improve the likelihood of adherence to long-term treatment.

PMID- 18727340
TI  - Mental stimulation, neural plasticity, and aging: directions for nursing research
      and practice.
AB  - An unprecedented increase in the number of older adults and consequent age
      related cognitive declines may negatively contribute to an already overwhelmed
      healthcare system. Many older adults report cognitive changes and express
      interest in methods to maintain cognitive functioning. Mental stimulation that
      consists of cognitively challenging activities is a means to facilitate neural
      plasticity, which can increase cognitive reserve and result in maintained or
      improved cognitive functioning. In addition, compensatory activities may provide
      mental stimulation that can improve cognitive functioning and increase cognitive
      reserve. Several mental stimulation (e.g., education, cognitive remediation
      therapy) and mental compensation (e.g., spaced retrieval method, method of loci)
      strategies are described in this article. Because nurses have a significant
      amount of direct contact with older adults, these strategies have important
      implications for nursing practice and research.

PMID- 18727341
TI  - Understanding the experience of living with spinal muscular atrophy: a
      qualitative description.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease
      caused by the progressive degeneration of motor neurons in the spinal cord. The
      disorder causes weakness and wasting of voluntary muscles. The purpose of this
      study was to describe the experience of living with SMA. Strategies used to
      manage symptoms and progression were also identified. Through e-mail
      communication, 11 participants were asked to respond to 5 questions about
      experiences with parents, family, friends, school, and healthcare providers, as
      well as provide demographic information. Participants were asked to describe
      their illness and the strategies used to optimize management. Data were analyzed
      in an ongoing manner through a constant comparative method. The experience of
      living with SMA was described as challenging and constantly changing. Four major
      themes were generated that described the experience of living with SMA:
      establishing strong relationships, normalizing and mainstreaming in society,
      using an innovative approach to symptom management, and maintaining optimism.
      Participants described both physical and emotional strategies for symptom
      management.

PMID- 18727342
TI  - Targeting nurse care. Interview by Louise Tweddell.

PMID- 18727343
TI  - 'Simulated practice is the way forward for training'.

PMID- 18727344
TI  - A tough test of our skills.

PMID- 18727345
TI  - Counting on core skills.

PMID- 18727346
TI  - A model for joint working. Interview by Jo Hartley.

PMID- 18727347
TI  - Guidance aims to cut antibiotic use in respiratory infections.

PMID- 18727348
TI  - Exploring the anatomy and physiology of ageing. Part 1--The cardiovascular
      system.

PMID- 18727349
TI  - Spinal opioids in postoperative pain relief. 2: Adverse effects.
AB  - This is a two-part unit on using spinal opioids to manage postoperative pain.
      Part 1 outlined the pharmacology of spinal opioids. Part 2 discusses the
      selection of patients and their nursing care. It also focuses on the incidence of
      and response to adverse effects. For further information on contraindications,
      nursing care and patients' clinical requirements, see Portfolio Pages on
      nursingtimes.net.

PMID- 18727350
TI  - 'All professionals share responsibility for improving learning disability care'.

PMID- 18727351
TI  - Eyes on the prize.
AB  - As the Beijing Olympics begin, there are many ambitious plans to improve public
      health when the games reach London in 2012.

PMID- 18727352
TI  - The human cost.

PMID- 18727353
TI  - My attempt to advocate for a vulnerable patient was in vain.

PMID- 18727354
TI  - Intravenous iron administration in a short-stay hospital setting.
AB  - Anaemia and iron deficiency are prevalent in the Western and developing world.
      They have implications for quality of life, prognosis and survival in a number of
      clinical settings. These range from the implications of anaemic status and
      associated outcomes in pregnancy, reduced blood transfusion requirements
      following surgery to lethargy and tiredness in older people if left unrecognised
      and untreated. Renal medicine is at the forefront of diagnosing and treating
      anaemia associated with chronic renal disease. In this arena the role of
      intravenous (IV) iron is well established. This article describes how IV iron may
      be given in total doses in a short-stay hospital setting.

PMID- 18727355
TI  - The effect of antipsychotic medication on metabolic syndrome.
AB  - This article highlights the need for mental health nurses to take a proactive
      role in the identification and prevention of metabolic syndrome to improve
      quality of life for patients with schizophrenia. A range of strategies to help
      mental health nurses address some of the physical health problems associated with
      metabolic syndrome in individuals with schizophrenia is outlined.

PMID- 18727356
TI  - Strategies to help nurses cope with change in the healthcare setting.
AB  - Working in health care has never seemed more exciting or stressful. The rapid
      changes made to the ways in which services are delivered, the search for
      economies of scale and role change adjustments designed to ensure that provision
      is timely and consumer friendly, all have the potential to create a stressful
      working environment. There are no longer jobs for life and nurses are required to
      perform new duties or to apply for posts that they once counted as their own.
      Although change does not need to be threatening, this article examines the
      experience when it is and recommends supportive ways of dealing with it.

PMID- 18727357
TI  - Lung cancer.

PMID- 18727358
TI  - Stand up for specialists.

PMID- 18727359
TI  - Demand and supply.

PMID- 18727360
TI  - Aim for the higher ground.

PMID- 18727361
TI  - [Coccidia (Eimeriida) from fishes of the continental waters of Russia].
AB  - Data on the Coccidia parasitizing fishes of 12 orders (Acipenseriformes,
      Clupeiformes, Salmoniformes, Anguilliformes, Siluriformes, Atheriniformes,
      Gadiformes, Gasterosteiformes, Syngnatiformes, Mugiliformes, Scorpaeniformes, and
      Pleuronectiformes) are given. Authors and year of description, synonymy,
      morphofunctional organization of exogenic stages, and list of hosts are presented
      for each coccidian species.

PMID- 18727362
TI  - [Taxonomic diversity of parasites in agnathans and fishes from the Volga River
      basin. VI. Acanthocephala, Hirudinea and Bivalvia].
AB  - The checklist of Acanthocephala, Hirudinea, and Bivalvia parasitizing agnathans
      and fishes in the Volga River basin is presented. Hosts and areas of distribution
      are indicated for each parasites species. The checklist includes 10 species of
      acanthocephalans, 7 species of leeches, and 9 species of Bivalvia (at the
      glochidium stage) from 45 fish species. None of the given parasite species is
      alien for the Volga River basin.

PMID- 18727363
TI  - [The influence of Myxidium gadi Georgievitsch, 1916 (Myxozoa: Myxosporea) on the
      level of lipid reserves in the tissues of the Black Sea whiting Merlangius
      merlangus euxinus at different periods of the annual cycle].
AB  - Concentration of total lipids and main lipid classes in the tissues of the Black
      Sea whiting males and females under different degrees of their infestation with
      the myxosporean Myxidium gadi is studied. Fishes were examined during the periods
      of fattening and spawning. Decrease of the total lipid (2-3 times) and
      triacylglycerol (3-4 times) concentration in the liver of heavily ingested males
      is revealed, as compared with the weakly infested fishes. However this effect has
      not been found in the fish females.

PMID- 18727364
TI  - [Vertical distribution of acanthocephalans of the order Echinorhynchida in Lake
      Baikal].
AB  - Vertical distribution of acanthocephalans of the order Echinorhynchida is studied
      in Lake Baikal. Four species and subspecies from cottid fishes (Perciformes:
      Cottoidei) were examined, namely Pseudoechinorhynchus borealis (Linstow, 1901),
      Metechinorhynchus salmonis salmonis (Muller, 1780), M.s. baicalensis Bogolepova,
      1957, M. truttae (Schrank, 1788). In the littoral (0-5 m) and sublittoral (5-100
      m) areas all these species and subspecies were occurred, white in the profundal
      (100-300 m) and abyssal (900-1600 m) areas only Metechinorhynchus salmonis
      baisalensis has been found.

PMID- 18727365
TI  - [On the occurrence of the nematode Oswaldocruzia filiformis (Strongylida:
      Molineidae) in Karelia].
AB  - Contents of the intestines of the viper Vipera berus (L., 1758) from Kizhi
      archipelago (Lake Onego) was examined. Helminth fauna of the viper was found to
      include single nematode species, Oswaldocruzia filiformis Goeze, 1782
      (Strongylida: Molineidae). Prevalence of the invasion was 60%, intensity of the
      invasion was 1-8 specimens per host, index of abundance was 1.92 specimens.
      Measurements and pictures of the parasite are given. Morphometric data on the
      nematode from viper are compared with those from other host species.

PMID- 18727366
TI  - [Detection of the West Nile Virus and its genetic typing in ixodid ticks
      (Parasitiformes: Ixodidae) in Tomsk City and its suburbs].
AB  - Four tick species, Ixodes persulcatus, I. pavlovskyi, I. trianguliceps, and
      Dermacentor reticulatus, were found in Tomsk and its suburbs in 2006. The species
      I. pavlovskyi was found to be dominant in the localities situated in Tomsk City,
      and I. persulcatus was dominant in its suburbs. Viral RNA and viral antigen of
      the West Nile virus (WNV) were detected in the ticks I. pavlovskyi and I.
      persulcatus collected in the city and its suburbs by the RT PCR method and enzyme
      immunoassay with monoclonal antibodies against protein E of the WNV. Average rate
      of the WNV infected ticks varied from 5.2 up to 11.7% in different localities.
      Identification of the nucleotide sequence of the protein E gene fragment allowed
      classifying the cDNA obtained as genotype Ia of the WNV. The sequences are proved
      similar to the strain LEIV-Vlg99-27889-human of the WNV isolated in Volgograd.
      The obtained data showed that natural foci of the WNV virus can appear in the
      city and its suburbs probably involving two dominant tick species. The WNV
      infected imagoes, larvae, and nymphs of I. persulcatus and I. pavlovskyi were
      collected from small mammals, lizards, and birds. Therefore we presume that these
      hosts can be involved in the circulation and distribution of WNV on the territory
      of Tomsk Region.

PMID- 18727367
TI  - [Morphology of the blackfly species group macropyga of the genus Prosimulium
      roubaud, 1906, and re-establishment of the generic name Taeniopterna Enderlein,
      1925 for this group (Diptera: Simuliidae)].
AB  - The genus Taeniopterna with the types species Melusina macropyga Lundstrom, 1911
      was proposed by Enderlein in 1925. Later this taxon was considered as the species
      group macropyga in the genus Prosimulium Roubaud, 1906 by many authors (Rubzov,
      1956; Crosskey et Howard, 1997; Adler et al., 2004, and others). However,
      differences between this group and the remaining species of Prosimulium s. str.
      (species group hirtipes/mixtum) seem to be not lesser, than those between other
      genera (or subgenera) of the tribe Prosimuliini (in our sense), namely Helodon
      Enderlein, 1921, Urosimulium Contini, 1963, Parahelodon Peterson, 1970, and
      Distosimulium Peterson, 1970. Taeniopterna differs from other genera of
      Prosimuliini by the following characters. Imago differs from all other genera in
      having shortened proboscic (1.5 times shorter than clypeus, while in other genera
      it is of the same length with clypeus). It differs from all genera except Helodon
      in having relatively prolonged and lightly pointed distally wings (in other
      genera wings are wide and rounded distally). Male differs from all other genera
      of the tribe, except Urosimulium, in having narrow frons between the eyes. It
      differs from the Urosimulium male by conic gonostyles (in Urosimulium gonostyles
      bear the large heel). Female differs from all other genera of tribe by very small
      spermatheca (1/3-1/5 of the lenght of the branch of genital fork (while in other
      genera spermatheca is equal or longer, than the branch of genital fork) and by
      the absence of serration on maxillae and mandibles. Female also differs from
      other genera of the tribe, except Prosimulium, by very long hypogynal valves and
      by missing or very small and pressed basal tooth of claws (in Helodon,
      Urosimulium, Parahelodon, and Distosimulium hypogynal valves are short and
      rounded, basal tooth of claws is moderate or large and put aside). It differs
      from Prosimulium by smaller head (more narrow than thorax, while in Prosimulium
      head is near equal by width with thorax) and by absence of sclerotization on the
      medial edges of hypogynal valves. Larva differs from all other genera of the
      tribe, except Prosimulium, in having long dorsoventral projections of wide
      sclerotized band of prothorax (in other genera this band is narrow and without
      projections). It differs from Prosimulium by another pattern of the hypostomal
      teeth. Pupa differs from all other genera of the tribe, except Distosimulium, by
      cocoon covering all the pupal body (in other genera cocoon covers only posterior
      part of the pupal body). It differs from Distosimulium by long and strong caudal
      thorns (in Distosimulium caudal thorns are of moderate length and more thin).
      These and some other characters give the base for the proposition to consider the
      species group macropyga as a a separate genus Taeniopterna Enderlein, 1925. A
      list of Taeniopterna species is given.

PMID- 18727368
TI  - [Characteristics of the parasite fauna of the perch Perca fluviatilis L. from the
      Bolshaya Lindalamba Lake in comparison with other small lakes in Karelia].
AB  - Parasite fauna of the perch Perca fluviatilis L. is investigated in the Bolshaya
      Lindalamba Lake, Republic of Karelia. It is shown, that formation of fish
      parasite fauna in small lakes depends mainly on the type of the lake ecosystem.

PMID- 18727369
TI  - [Eimeria of cattle in the Republic of Dagestan].
AB  - Data on Eimeria (Sporozoa: Coccidia) parasitizing cattle in different regions of
      the Republic of Dagestan are given. Eight species of the genus were found.
      Eimeria zuernii, E. subspherica, and E. bovis appeared to be the dominate
      species. Total infestation rate in the republic is 67.7%, while in mountain
      regions of Dagestan in is 83%.

PMID- 18727370
TI  - [Learning and extinction of passive avoidance in mice with high predisposition to
      catalepsy].
AB  - The passive avoidance learning and extinction in mice strain ASC with high
      predisposition to catalepsy as compared with mice of CBA and AKR strains were
      analyzed. Impairment of fear extinction as a major symptom of depression was
      revealed in ASC mice, whereas a delay of extinction in CBA mice and fast
      formation of new inhibitory learning in AKR mice were found. It is suggested that
      the long persistence of fear in ASC mice results from increased anxiety during
      the repeated presentation of a context in the absent of aversive stimulus. Defect
      of fear inhibition in ASC mice makes it possible to use this strain of mice as
      genetic model of depression.

PMID- 18727371
TI  - [Attention parameters in visual search tasks in various human age groups].
AB  - The visual search performance was investigated in two children (5 and 7-years
      old) and three adult groups (15, 20--and 35 and up to 60-years-old). The results
      of adults were similar among themselves and therefore were taken as a control set
      for children group results. We used 5 sorts of visual tasks, one difficult task
      and four easy tasks for adults with a target differing from counter-irritation.
      Children's results were worse than adults' those: the search time was longer and
      children made plenty of errors (false alarms end misses of targets). We suggest
      that children's attention system was less effective than adults' one in result of
      frontal, parietal and temporal cortical structure activation deficit. It follows
      that attention system is completely developed by 15 years of age in humans.

PMID- 18727372
TI  - [Interhemispheric connections of ocular-dominance columns in cats with binocular
      vision impairment].
AB  - We have investigated the interhemispheric connections of areas 17 and 18 in cats
      with impaired binocular vision (monocular deprivation, uni- and bilateral
      strabismus). Monosynaptic neuronal connections were studied using
      microionophoretic injections of horseradish peroxidase in the single cortical
      columns and analsys of spatial distribution of retrogradely labelled callosal
      cells was performed. In the cases of monocular deprivation and strabismus, the
      spatial asymmetry and eye-specificity of interhemispheric connections are
      retained. Quantitative changes of connections are more pronounced in strabismic
      cats. In cats with binocular vision impairments, as well as in control ones, the
      width of callosal-recipient zone is larger than of the callosal cells zone. This
      may indicate that interhemispheric connections are non-reciprocal in the areas of
      cortex that are more distant from the projection of vertical meridian of visual
      field. We expect that there should be morpho-functional in the cells that are
      providing connections in opposite directions.

PMID- 18727373
TI  - [Human magno- and parvo-systems and selective disruptions in their function].
AB  - In psychophysical and electrophysiological investigations, we tested the
      hypothesis that in patients with multiple sclerosis at its early stage either
      phasic cells of the magnocellular pathway or tonic cells of the parvocellular
      pathway are disturbed. Healthy humans and patients with early stage of diseases
      have a contrast spatial-frequency sensitivity measure. The decrease in
      sensitivity at low, medium and high spatial frequency indicates changes in parvo-
      and magno-system activity. The data are separated into two clusters.
      Psychophysical data is in good accordance with electrophysiological data of
      visual evoked potentials (VEPs). First group of patients showed changes of the
      amplitude of positive wave P100 whereas in second group of patients changes of
      negative wave N80 dominated comparative to healthy subjects. According to some
      literature data these changes were specific for M-pathway and for P-pathway.

PMID- 18727374
TI  - [Correlation between the EEG coherence and recognition of emotions in speech].
AB  - Analysis of the EEG in 2 extreme groups: subjects with high and low indexes of
      identification of emotional intonation, was carried out. The number of pairs of
      electrode sites with significant differences in coherence was compared at rest
      and during the emotion identification task in 6 standard frequency bands. The
      data revealed that, in general, coherence is higher in the group with low
      identification rates.

PMID- 18727375
TI  - [Baroreflexes originated in vertebral artery zones upon peripheral vein tonus,
      systemic arterial blood pressure, and external respiration].
AB  - The investigation was intended to study the role ofbaroreceptors
      ofhemodynamically isolated zone of vertebral arteries in regulation of peripheral
      veins tonus, arterial pressure and external respiration. Pressure decrease in
      this vascular reflexogenic zone led to reflex responses of increase in femoral
      vein tonus, elevation of blood pressure level and stimulation of external
      respiration. The opposite reflex responses of cardio-respiratory functional
      system to initial pressure activation of vertebral arteries baroreceptors are
      observed. Basing on generalization of our own findings and similar physiological
      and morphological researches of other authors, it is established that
      afferentation from the vertebral artery zone is a reflexogenic factor of somatic
      muscles' veins tonus regulation. These reflexes of capacity vessels tonic
      activity changes are part of cardio-respiratory responses of maintaining the
      tissue gaseous exchange.

PMID- 18727376
TI  - [Effect of ectopic excitation on the ventricular pump function in chicken].
AB  - The pump function of the heart ventricles was studied in chest-open anaesthetized
      adult female chickens under sinus rhythm and ectopic excitation of different
      localization. The intraventricular pressure in the right and left heart
      ventricles was measured by insertion of catheters through the ventricular free
      walls. Maximum systolic pressure, end-diastolic pressure, contractility
      (dP/dtmax) and relaxation (dP/dtmin) of both heart ventricles, and duration of
      the asynchronous contraction time of the left ventricle were analyzed. It was
      revealed that reduction of the pump function of the left ventricle tends to be
      greater under right ventricular ectopic excitation compared with left ventricular
      one. In comparison with the sinus rhythm, the pump function of the right
      ventricle was preserved to a greater extent under stimulation of the left
      ventricular apex and was significantly impaired under right ventricular ectopic
      excitation. Relaxation of both heart ventricles was more susceptible to
      ventricular ectopic excitation than contractility, and was more vulnerable in the
      right ventricle than in the left one. The direction of changes of the pump
      function of the heart ventricles in chickens under ventricular ectopic excitation
      was similar to changes of the pump function of mammalian hearts.

PMID- 18727377
TI  - [Cholinergic mechanisms of the hypothalamus medial preoptic area in control of
      thermoregulation and of wakefulness-sleep states in pigeons].
AB  - The data obtained show that cholinergic mechanisms of the medial preoptic area of
      hypothalamus participate in control of wakefulness-sleep states and
      thermoregulation parameters in pigeons. Muscarinic and nicotinic cholinergic
      receptors are established to be involved in the wakefulness maintenance. The
      muscarinic cholinergic receptor activation of the medial preoptic area is
      accompanied by an elevation of the brain temperature, by development of
      peripheral vasoconstriction, and by an in increase in level of the muscle
      contractile activity. During the nicotinic cholinergic receptor activation of the
      area, a decrease in the brain temperature and an increase in level of the muscle
      contractile activity are found. A comparative analysis of experiments and early
      investigation suggests that during the cholinergic receptors activation changes
      in the brain temperature of pigeons depend on type of the cholinergic receptors
      but not on their localization in the preoptic area of hypothalamus.

PMID- 18727379
TI  - [Effects of desensitization of capsaicin-sensitive afferent neurons on gastric
      microcirculation in rats depend on the blood glucocorticoid hormone level].
AB  - The effects of desensitization of capsaicin-sensitive afferent neurons on gastric
      microcirculation were investigated before and after administration of
      indomethacin at ulcerogenic dose in adrenalectomized rats with or without
      corticosterone replacement and in sham-operated animals. We estimated the blood
      flow velocity in submucosal microvessels; the diameters and permeability of
      mucosal venous microvessels as parameters of gastric microcirculation.
      Desensitization of capsaicin-sensitive neurons was performed with capsaicin at
      the dose 100 mg/kg two weeks before the experiment. Adrenalectomy was created one
      week before experiment. In vivo microscopy technique for the direct visualization
      of gastric microcirculation and the analysis of the blood flow was employed.
      Indomethacin at ulcerogenic dose decreased the blood flow velocity in submucosal
      microvessels, caused dilatation of superficial mucosal microvessels and increased
      their permeability. Desensitization of capsaicin-sensitive afferent neurons
      potentiated indomethacin-induced microvascular disturbances in gastric submucosa
      mucosa. These potentiated effects of the desensitization are obviously promoted
      by concomitant glucocorticoid deficiency. Thus, glucocorticoid hormones have a
      beneficial effect on gastric microcirculation in rats with desensitization of
      capsaicin-sensitive afferent neurons.

PMID- 18727378
TI  - [Mechanism of strengthening of the contractile activity in the duodenum and in
      the jejunum in psychogenic stress in rabbits].
AB  - In experiments on unanaesthetized rabbits myoelectric activity (contractile
      activity index) of proximal (postpyloric) and distal sites of duodenum, and
      proximal part of jejunum was studied under stress induced by fastening a rabbit
      to a table in supine position. In both sites of duodenum, the stress impact
      induced a short-time decrease of contractile activity which was followed by its
      increase that exceeded the initial level. In the proximal part ofjejunum, the
      increase of contractile activity took place only during the second part of stress
      response. The strengthening of the contractile activity of the proximal part of
      duodenum was preserved after muscarinic or nicotinic cholinoceptor blockage, and
      after beta-receptor blockage. It was concluded that the contractile response of
      the proximal part of duodenum did not result from the contribution of central or
      local neurogenic mechanism, including excitatory cholinergic one, but was humoral
      in origin. The strengthening of the contractile activity of the distal part of
      duodenum and proximal part ofjejunum was abolished by muscarinic cholinoceptor
      and beta-receptor blockage, and resulted from the action of circulating
      catecholamines on the excitatory beta-adrenoceptor, localized on the cholinergic
      neurones of the enteric nervous system.

PMID- 18727380
TI  - [Redox-dependent regulation of apoptosis as a function of intracellular reactive
      oxygen species in oxidative stress].
AB  - Programmed cell death of mononuclear cells in conditions of oxidative stress in
      vitro and selective inhibitors of MAP-kinases JNK, p38 were investigated. Levels
      of active and inactive forms of MAP-kinases, factors of transcription P53, NF-kB
      and proteins-regulators of apoptosis Bcl-X(L), Bad, Bcl-2 were determined by
      immunoblotting (Western blotting). The increasing of number of annexin-plus
      mononuclears/lymphocytes in the culture associated with enhance of the level of
      intracellular reactive oxygen species was shown. The treatment of selective
      inhibitors JNK SP600125 and p38 ML3403 in vitro prevents peroxide-induced
      appearance of P53 and NF-kB in blood mononuclear cells, associated with
      increasing of their apoptotic activity. The disturbance of the balance of pro-
      and antiapoptotic proteins of Bcl-2, family (the increase of the Bax level
      without changes of Bcl-X(L) and Bcl-2) leads to the growth of apoptosis process
      of mononuclear leucocytes activity in oxidative stress conditions.

PMID- 18727381
TI  - [Monoamines and reproductive function of rats selected for strengthening of
      catatonia response].
AB  - Weights of the body, ovaries, and uterus; estrous cycles and the contents of
      dopamine (DA) and norepinephrine (NE) in the hypothalami, and testosterone in
      blood plasma of GC females were studied at various estrous stages (diestrus and
      estrus). The outbred Wistar line was used as a control. In addition to reduced
      body weight in GC females, we observed disturbed morphological cyclic linkages
      between the ovaries and uterus: ovary weight reduction in diestrus (p < 0.01) and
      lower estrogen-related increase in uterus weight in estrus in GC females in
      comparison with Wistar ones. While the contents of DA and NE in GC hypothalami
      were reduced, the levels of these monoamines were high in estrus and low in
      diestrus. Testosterone levels in GC female plasma in diestrus were higher than in
      estrus or in Wistar rats.

PMID- 18727382
TI  - [Molecular genetics of Usher syndrome].
AB  - Usher syndrome (USH) is inherited in an autosomal recessive mode. The disease is
      characterized by hearing loss, progressing vision loss, and vestibular
      dysfunction. In most cases, it is the reason for deafness and blindness in school
      age children. The prevalence of USH in the main population is estimated as 4.4
      per 100,000 individuals, approximately. The prevalence of heterozygous carriers
      can reach 1 per 70 normally hearing individuals. There is currently no effective
      treatment of USH. The patients are provided with hearing aids, but, in case of
      severe hearing impairement these aids give no effect. In view of this, developing
      diagnostic methods is important. It is believed that molecular genetic
      investigations will enable early diagnostics of the syndrome.

PMID- 18727383
TI  - [Distribution of two chromosome races of the common shrew (Sorex araneus L.) in
      the hybrid zone: may a change of the dispersal mode maintain independent gene
      frequencies?].
AB  - Combination of different dispersal modes may itself, without external obstacles,
      lead to the appearance of subdivided populations and maintain the existence of
      independent population systems. The common shrew, a mammal convenient for
      studying different levels of intraspecific differentiation, was the object of the
      study. Empirical data have been used for simulation taking into account the
      change of dispersal modes in the population area. The obtained results agree with
      empirical data on the distribution of races and hybrids in the hybrid zone of
      chromosome races Moscow and Seliger. Change of the dispersal mode may maintain
      independent population dynamics and, in the case of chromosome races, prevent the
      migration of parental individuals into the territory of the other race.

PMID- 18727384
TI  - [Distribution of induced chromosome rearrangement breakpoints along the
      chromosome length and the problem of intercalary heterochromatin in Drosophila
      melanogaster].
AB  - Historically, the term "intercalary heterochromatin" was based on the finding
      that induced chromosome rearrangements occur at a higher frequency in the
      corresponding regions. The available molecular genetic data and, in particular,
      the results of the Drosophila Genome Project made it possible to decide between
      two possible explanations of the preferential location of chromosome
      rearrangement breakpoints in intercalary heterochromatin regions. Namely, a
      higher frequency of radiation-induced rearrangements in these regions correlates
      with the DNA content and probably lacks an association with the features of
      chromatin organization.

PMID- 18727385
TI  - [Heterochromatic DNA repeats in Drosophila and unusual gene silencing in yeast
      cells].
AB  - The 1.25-kb heterochromatic Stellate repeats of Drosophila melanogaster are
      capable of stably persisting in transgenic constructs and silencing the white
      reporter gene (mosaic position effect variegation). This system reveals an
      unusual form of silencing, which is insensitive to known modifiers of position
      effect variegation. The unusual form of silencing was studied with yeast
      Saccharomyces cerevisiae, a simple eukaryotic model. To be transferred into yeast
      cells, the D. melanogaster Stellate repeats were cloned in the pYAC4 centromeric
      vector (CEN4, URA3, TRP1, HIS3). The HIS3 and/or URA3 genes could be inactive in
      plasmids consisting of pYAC4 and the Stellate insert in yeast cells. Deletion of
      D. melanogaster DNA from the plasmid was found to activate the URA3 and HIS3
      genes. It was assumed that the genes were repressed rather than damaged in the
      presence of the Stellate repeats and that a new form of gene silencing was
      revealed in S. cerevisiae.

PMID- 18727386
TI  - [Interaction between checkpoint genes RAD9, RAD17, RAD24, and RAD53 involved in
      the determination of yeast Saccharomyces cerevisiae sensitivity to ionizing
      radiation].
AB  - Mechanisms for genetic control of cell division cycle (checkpoint control) have
      been studied in most detail in yeast Saccharomyces cerevisiae. To clarify the
      role of checkpoint genes RAD9, RAD17, RAD24, and RAD53 in cell radioresistance,
      double mutants were analyzed for cell sensitivity to ionizing radiation. Double
      mutants carrying mutations in combination with mutation rad9delta were shown to
      manifest the epistatic type of interaction. Our results suggest that checkpoint
      genes RAD9, RAD17, RAD24, and RAD53 belong to a single epistatic group designated
      RAD9 and govern the same pathway. Genes RAD9 and RAD53 have a positive effect on
      sensitivity to gamma-radiation, whereas RAD17 and RAD24 have a negative effect.
      Interactions between mutations may differ when considering their sensitivity to
      gamma-radiation and UV light; mutations rad9delta and rad24delta were shown to
      manifest the additive effect in the first case and epistatic effect in the
      second.

PMID- 18727387
TI  - [Systemic regulation of genetic and cytogenetic processes by a signal cascade of
      actin remodeling: locus agnostic in Drosophila].
AB  - The concept on systemic regulation of genetic and cytogenetic processes has
      acquired a new perspective after the completion of the Human Genome project, when
      the view on systemic realization of genetic activity in the dynamic spatial
      organization of the genome is the nucleus was generally accepted. This
      organization underlies plasticity of complex biological systems. Chromosome
      position within the nucleus determined both processes of normal development and
      the development of genomic diseases, i.e., changes according to the environmental
      requirements, current needs of the organism, and its individual experience.
      Nuclear actin has been envisioned as a main factor bridging three levels of the
      genome organization (nucleotide, structural, and spatial), due to its capability
      of (1) regulating transcription by activating all three classes of RNA
      polymerase; (2) participating in chromatin remodeling by interacting with
      numerous proteins; and (3) lining the nuclear membrane, determining the
      chromosome attachment points and regulating export from the nucleus. In view of
      this, the role of actin remodeling factors (LIMK1, cofilin, actin) in the
      development of neurodegenerative diseases, including prionic ones, and in the
      mechanisms of generation of genomic diseases, syndromes resulting from unequal
      recombination, has been intensely studied. Drosophila is a helpful model organism
      to determine the sequence of events in this system of hierarchical relationships.
      Using spontaneous and mutant variants of the agnostic locus, we have designed a
      model of the Williams syndrome, which also reproduces main diagnostic traits of
      neurodegenerative diseases.

PMID- 18727389
TI  - [Frequency of chromosomes carrying endogenous retroviruses in the populations of
      domestic pig and wild boar].
AB  - Statistical analysis of the frequency of chromosomes carrying three types (A, B,
      and C) of porcine endogenous retroviruses (PERV) was based on molecular-genetic
      testing of populations of domestic pigs and wild boars. Domestic pigs were shown
      to have higher frequency of PERV and haplotypes containing two and three types of
      PERV than wild boars.

PMID- 18727388
TI  - [Polymorphism of the 12S rRNA gene and phylogeography of the Central Asian
      tortoises Agrionemys horsfieldii gray, 1844].
AB  - Based on intraspecific polymorphism of 12S rRNA gene, genetic variation of
      isolated populations of the Central Asian tortoise, Agrionemys horsfieldii, was
      for the first time investigated on a large part of the species distribution
      range, encompassing Uzbekistan, southern Kazakhstan, and northern and eastern
      Iran. In 59 tortoises, four haplotypes were discovered, including two (AH1 and
      AH2), described earlier. Haplotype AH1 was detected in 52 tortoises, inhabiting
      southern Kazakhstan and Uzbekistan. Haplotype AH2 was found in four tortoises
      from the border territory between Uzbekistan, Tajikistan, and Afghanistan. Two
      novel haplotypes, AH3 and AH4, were detected in the three tortoises from Iran.
      Based on nucleotide substitutions in the 12S rDNA sequence, the possible
      divergence time between the tortoises from different parts of the range was
      estimated. Possible pathways of the formation of modern intraspecific groups of
      A. horsfieldii are discussed.

PMID- 18727390
TI  - [Comparative analysis of diploid species of Avena l. using cytogenetic and
      biochemical markers: Avena canariensis baum et fedak and A. longiglumis dur].
AB  - The diploid oat species containing the A genome of two types (Al and Ac) were
      studied by electrophoresis of grain storage proteins (avenins), chromosome C
      banding, and in situ hybridization with probes pTa71 and pTa794. The karyotypes
      of the studied species displayed similar C-banding patterns but differed in size
      and morphology of several chromosomes, presumably, resulting from structural
      rearrangements that took place during the divergence of A genomes from a common
      ancestor. In situ hybridization demonstrated an identical location of the 45S and
      5S rRNA gene loci in Avena canariensis and A. longiglumis similar to that in the
      A. strigosa genome. However, the 5S rDNA locus in A. longiglumis (5S rDNA1) was
      considerably decreased in the chromosome 3A1 long arm. The analysis demonstrated
      that these oat species were similar in the avenin component composition, although
      individual accessions differed in the electrophoretic mobilities of certain
      components. A considerable similarity of A. canariensis and A. longiglumis to the
      Avena diploid species carrying the As genome variant was demonstrated.

PMID- 18727391
TI  - [Genetic control of fasciation in pea (Pisum sativum L.)].
AB  - The inheritance and manifestation of fasciation character in three fasciated
      lines of common pea Pisum sativum L. were investigated. All studied forms are
      characterized by abnormal enlargement of stem apical meristem leading to
      distortions in shoot structure. It was estimated that fasciation in mutant
      Shtambovyi is connected with recessive mutation in gene FAS, which was localized
      in linkage group III using morphological and molecular markers. It was
      demonstrated that fasciation in cultivar Rosacrone and line Lupinoid is caused by
      recessive mutation of the same gene (FA). The peculiar architecture of
      inflorescence in the Lupinoid line is a result of interaction of two recessive
      mutations (det fa). Investigation of interaction of mutations fa and fas revealed
      that genes FA and FAS control consequential stages of apical meristem
      specialization. Data on incomplete penetrance and varying expressivity were
      confirmed for the mutant allele fa studied.

PMID- 18727392
TI  - [Hordein locus polymorphism in near eastern local populations of cultivated
      barley (Hordeum vulgare L.)].
AB  - Electrophoresis in starch gel has been used to study the polymorphism of hordeins
      encoded by loci Hrd A, Hrd B, and Hrd F in 140 local barley populations from the
      Near East, including 60, 34, 33, 8, and 5 populations from Syria, Jordan, Iraq,
      Palestine, and Israel, respectively. Fifty-seven Hrd A, 87 Hrd B, and 5 Hrd F
      alleles have been found. The alleles of these loci considerably differ in
      frequencies and distribution in populations from different Near Eastern
      countries. Cluster analysis of the matrix of the frequencies of hordein locus
      alleles in barley populations from the Near East, North Africa, Ethiopia, and
      South Arabia has yielded two clusters. The first cluster includes barley
      populations from Israel, Palestine, Morocco, Tunisia, Algeria, and Egypt; the
      second cluster, populations from Iraq, Syria, Jordan, Yemen, and Ethiopia.

PMID- 18727393
TI  - [Analysis of chromosomal localization of loci controlling milk production traits
      in cattle].
AB  - Analysis of the pattern of the chromosomal localization of quantitative trait
      loci (QTLs) is necessary for comprehensively understanding their functions. The
      chromosomal localization of QTLs controlling milk production traits has been
      studied in cattle chromosomes. The distribution of QTLs between chromosomes has
      proved to be binomial. Their distribution along each chromosome was, in general,
      uniform, except for the QTLs controlling the somatic cell score (SCS), which
      tended towards telomeric location. However, there are chromosomes either enriched
      with or particularly poor in QTLs. The QTL distribution patters are the most
      similar for the milk yield (M) and milk protein yield (P) and for milk fat yield
      (F) and milk fat content (%F). The pattern of the SCS QTLs stands out among those
      of other QTLs. The distance between the QTLs of contrasting traits is the
      shortest for M and P QTLs, longer for M and milk protein content (%P) QTLs, and
      still longer for M and %F QTLs, which may be explained by QTL pleiotropy, a
      common phenomenon in cattle.

PMID- 18727394
TI  - [The effect of artificial selection for coat color on fitness in a farm
      population of the sable (Martes zibellina)].
AB  - The relationship between the response to artificial selection for darker coat
      color and fitness in a farm population of the sable (Martes zibellina L.) from
      the Pushkinskoe Fur Farm (Moscow oblast) was studied. The selection was performed
      during 41 years. By the moment of the study, a response to the selection for this
      character had been obtained: the coat color in the selected population had become
      darker, and the proportion of black animals in it increased. In addition, sables
      with black heads, which were absent in the original population, had appeared.
      Artificial selection was accompanied by a decrease in the fitness of the selected
      population, which was expressed in decreased female reproductive capacity
      parameters (the fertility, maturation rate, and duration of the reproductive
      period). A selection technique consisting in the use of only highly fertile
      animals in the selection originally made it possible to restore the fitness
      parameters to the initial level almost without a decrease in the dark shade of
      the fur. However, further selection led to a drastic decrease in fitness that
      could not be precluded by any selection method used. The possible ways to
      overcome this unfavorable effect of artificial selection are discussed.

PMID- 18727395
TI  - [Genetic differentiation of subspecies of the house mouse Mus musculus and their
      taxonomic relationships inferred from RAPD-PCR data].
AB  - Genetic differentiation of six subspecies of the house mouse Mus musculus (Mus
      musculus musculus. M. m. domesticus, M. m. castaneus, M. m. gansuensis, M. m.
      wagneri, and M. m. ssp. (bactrianus?) was examined using RAPD-PCR analysis. In
      all, 373 loci of total length of about 530 kb were identified. Taxon-specific
      molecular markers were detected and the levels of genetic differences among the
      subspecies were estimated. Different degree of subspecific genetic
      differentiation was shown. The most similar subspecies pairs were M. m. castaneus
      -M. m. domesticus and M. m. musculus--M. m. gansuensis. In our phylogenetic
      reconstruction, M. m. wagnery proved to be most different from all the other
      subspecies. Genetic distances between it and other subspecies were two- to
      threefold higher than those between the "good"' species of the subgenus Mus
      (e.g., between M. m. musculus and M. spicilegus, M. musculus and M. abbottii).
      The estimates of genetic similarity and the taxonomic relationships between six
      house mouse subspecies inferred from RAPD partially conformed to the results
      based on cytogenetic and allozyme data. However, they were considerably different
      from phylogenetic reconstructions based on sequencing of the control mtDNA
      region, which reflects mutual inconsistency of different systems of inheritance.

PMID- 18727396
TI  - [Analysis of reproductive and age parameters in Kalmyk rural populations].
AB  - Questionnaire data of 704 women of postreproductive age were used in this study.
      Questionnaire involved 462 Kalmyks, 119 Russians, 43 Kazakhs, 52 representatives
      of Northern Caucasus ethnic groups and, 28 other ethnic groups. The average
      number of pregnancies in Kalmyks was 5.49; the average number of live births was
      3.21. The Crow index for Kalmyks was I(m) = 0.038, I(f) = 0.300, I(tot) = 0.350;
      and for Russians in Kalmykia, I(m) = 0.030, I(f) = 0.264, I(tot) = 0.302.

PMID- 18727397
TI  - [Cytogenetic analysis of genotoxic effects in subjects employed in heat power
      industry].
AB  - Chromosomal aberration rate has been estimated in peripheral blood lymphocytes of
      subjects occupationally exposed to a set of hazardous factors (employees of the
      Kemerovo Heat Power Plant). The frequency of metaphases with aberrations in the
      workers (3.23 +/- 0.26%, N = 104) is significantly higher than in control
      subjects (2.11 +/- 0.28%, N = 70). The cytogenetic aberrations did not depend on
      the sex, age, duration of employment, or smoking.

PMID- 18727398
TI  - [On the relation of the microtubule length and dynamics: boundary effect and
      properties of an extended radial array].
AB  - In interphase cells, microtubules (MT) are long and form extended radial array.
      The length of individual MTs in living cells exhibits substantial stochastic
      fluctuations while the average length distribution in a cell remains nearly
      constant. We present a quantitative model that describes relation of the MT
      length and dynamics in the steady state in the cell using the minimal set of
      parameters (cell radius, tubulin concentration, critical concentration for plus
      end elongation, and the number of nucleation sites). The MT array is approximated
      as a radial system, where MT minus ends are associated with the nucleation sites
      on the centrosome, while plus ends grow and shorten. Dynamic instability of MT
      plus ends is approximated as a random walk process with boundary conditions and
      the behavior of MT array is quantified using diffusion and drift coefficients
      (Vorobjev et al., 1997, 1999). We show that establishment of the extended steady
      state array could be accomplished solely by the limitation of the MT growth by
      the cell margin. We determined for the cell radius, tubulin concentration,
      critical concentration for plus end elongation, and number of nucleation sites
      the reference point in the parameter space where plus ends of individual MT on
      average neither elongate nor shorten. In this case average length of MT is equal
      to the half of cell radius. When any parameter is shifted from its reference
      value MTs become longer or shorter and consequently acquire positive or negative
      drift of their ends. In the vicinity of reference point, change in any parameter
      has major effect on the MT length and rather small effect on the drift. When mean
      length of the MTs is close to the cell radius the drift of the free plus ends
      becomes substantial, resulting in processive growth of individual MTs in the
      internal cytoplasm accompanied by apparent stabilization of the plus ends at the
      cell margin. Under these conditions small changes in parameters have significant
      impact on the magnitude of drift. Experimental analysis of the MT plus ends
      dynamics in different cultured cells shows that in most cases plus ends display
      positive drift, which, in the framework of the presented model, is in agreement
      with the simultaneous presence of long MTs.

PMID- 18727399
TI  - [Inhibition of functional activity of macrophages in vitro by dimer RNase
      Bacillus intermedius].
AB  - The influence of cross-linked by dimethylsuberimidate dimeric RNAse from Bacillus
      intermedius on peritoneal rat macrophages has been investigated in vitro. It has
      been shown that dimeric RNase with concentrations of 0.5-40.0 mg/ml decreases the
      functional activities of macrophages. This is manifested in the inhibition of the
      phagocyte function of macrophages and suppression of the fusion of phagosomes
      with lysosomes. The change in the cytoplasmatic membrane surface structure
      induced by the dimers, which is stronger than that induced by monomers, has been
      demonstrated using atomic force microscopy. The role of membrane properties
      modification in the inhibition effect of RNase dimers on the functional
      activities of macrophages is discussed.

PMID- 18727401
TI  - [Fine structure of glial cells in the central nervous system of the tapeworm
      Grillotia erinaceus (Cestoda: Trypanorhyncha)].
AB  - The problem of glial cells existing in parasitic and free living flatworms is
      correlated with organization of parenchyma in platyhelmintes. In the contrary to
      the widespread opinion that myelin-like envelopes and glial cells do not exist in
      the nervous system of parasitic flatworms, it has been shown by ultrastructural
      researches that Amphilina foliacea (Cestoda, Amphilinidea) has well developed
      glial cells and myelin-like envelopes in the ganglia and main cords, which
      include both glial cells and intercellular components. The aim of our research
      was to reveal and investigate in details structural components corresponding to
      the concept of the glial cell in the CNS of Grillotia erinaceus (Cestoda:
      Trypanorhyncha). Three types of glial cells have been found. The first type is
      the fibroblast-like glial cells; cells locate in the cerebral ganglion, contain
      in cytoplasm and extract out fibrillar matrix, form desmosomes and have
      supporting function. The glial cells of the second type form myeline-like
      envelope of the giant axons and bulbar nerves in scolex and have laminar
      cytoplasm. These cells are numerous and exceed in number the neurons bodies into
      the nerve. The glial cells of the third type form multilayer envelopes in the
      main nerve cords; extra cellular fibers and gap-junctions take place between the
      layers. There are contacts between the glial cells of the third type and
      excretory epithelium but specialized contacts with neurons have been not found.
      The existing of glial cells in free living and parasitic flatworms is discussed.

PMID- 18727400
TI  - [Autocrine factor participation in defence of cytotoxic CTLL-2 cells from
      oxidative stress].
AB  - The role of autocrine factors (AF) secreted by cytotoxic IL-2-dependent CTLL-2
      cells along with pyruvate in cell defense from oxidative stress was investigated.
      The addition of conditioned medium (CM) containing pyruvate and AF into CTLL-2
      cell cultures increased significantly cell survival under oxidative stress
      condition. The kinetics of hydrogen peroxide removal from cell cultures under
      oxidative stress in the case of CM addition has been obtained. The removal of
      H2O2 mostly by means of its reaction with pyruvate that is contained in CM has
      been shown at the beginning of oxidative stress (up to 15 min). Pyruvate content
      in CM was determined as 138 +/- 7 microM. Cell filtration on column with Bio-Gel
      P-10 was used for removal pyruvate from CM. Three fractions of CM (A, B and C)
      were obtained as a result of gel filtration. Pyruvate was not detected in any
      fraction. The fraction A was eluted from column as the first one and contained
      the largest molecules. Cell survival test showed the fraction B to have the
      highest ability to protect CTLL-2 cells under oxidative stress. The fraction A
      supported cell survival to a less degree and fraction C was shown to have no
      protective ability. The addition of the fraction B to the cell cultures resulted
      in preservation of significantly higher intracellular ATP level in the cells
      under oxidative stress than in the control ones. Moreover, AF of the fraction B
      was shown to react directly with hydrogen peroxide and inactivate it in the
      absence of cells. AF of the fraction A did not have such properties.

PMID- 18727402
TI  - [Some aspects of the regeneration process carried out by means of pluripotent
      stem cells].
AB  - This work is devoted to the vital topic of regeneration by stem cells. Cells
      predecessors and differentiated cells can divide a limited number of times
      (Alberts et al., 1994) and are not capable of providing tissue regeneration
      throughout the ontogenesis. The tissue renewal during such a long period is
      impossible without participation of a specialized system responsible for
      regeneration. The given system is submitted by stem cells which are capable of
      being differentiated in all types of somatic cells and in a line of germ cells,
      and also have ability to self-renew during the whole life of an organism. Results
      of our research suggest that stem cells make up a universal mechanism of
      regeneration which has been formed during evolution.

PMID- 18727403
TI  - [Cell therapy for myocardial infarction].
AB  - The review discusses cell therapy; one of the most promising approaches to
      myocardial infarction treatment. The possibility to use cell material of various
      origins is analyzed. The review sums up data on the application of fetal and
      neonatal cardiomyocytes, myoblasts, bone marrow mononuclear fraction,
      hematopoietic and mesenchymal stem cells (MSX) as cell therapy agents. The
      conclusion is made that MSC are promising cell material for myocardial infarction
      therapy. MSC are able to migrate to the injured area, differentiate into
      myocardial lineage. They produce a wide range of factors that stimulate
      angiogenesis and increase viability of cells, including cardiomyocytes.

PMID- 18727404
TI  - [The reentrant binomial model of nuclear anomalies growth in rhabdomyosarcoma RA
      23 cell populations under increasing doze of rare ionizing radiation].
AB  - Distributions of nuclear morphology anomalies in transplantable rabdomiosarcoma
      RA-23 cell populations were investigated under effect of ionizing radiation from
      0 to 45 Gy. Internuclear bridges, nuclear protrusions and dumbbell-shaped nuclei
      were accepted for morphological anomalies. Empirical distributions of the number
      of anomalies per 100 nuclei were used. The adequate model of reentrant binomial
      distribution has been found. The sum of binomial random variables with binomial
      number of summands has such distribution. Averages of these random variables were
      named, accordingly, internal and external average reentrant components. Their
      maximum likelihood estimations were received. Statistical properties of these
      estimations were investigated by means of statistical modeling. It has been
      received that at equally significant correlation between the radiation dose and
      the average of nuclear anomalies in cell populations after two-three cellular
      cycles from the moment of irradiation in vivo the irradiation doze significantly
      correlates with internal average reentrant component, and in remote descendants
      of cell transplants irradiated in vitro - with external one.

PMID- 18727405
TI  - [Gytogenetics of Chironomus riparius L. from the fishpond in Borok village
      (Diptera, Chironomidae)].
AB  - We have found three inherited inversions in Chironomus riparius populations from
      the Borok fishpond, namely: (A3d-B1a) in the arm A (C5a-C6a) in the arm D and
      (B3b-4d/e) in the arm F. Increase of heterochromatin in some bands of chromosome
      F (B3h, B3h + B3c--C1a) and puffs appearance in the arms C, D and E have been
      observed. We saw also changes in functional activity of nucleolar organizer (N)
      and Balbiani rings (BRe/BRb). It has been found that some of inversion
      breakpoints coincide with the Alu and Hinf satellite DNA localization sites.

PMID- 18727407
TI  - [Variability of stoma's guard cells in Lilium].
AB  - It has been revealed, that the parameters of stoma's guard cells in the leaves of
      some lilies considerably vary depending on plant age, the tier of leaves, and the
      place of stoma location on a leaf. Lengths of stoma's guard cells in bottom parts
      of leaves reliably exceeded those lengths in the middle parts in the majority of
      the hybrids studied. The latter are larger in juvenile plants.

PMID- 18727406
TI  - [The geographic varyability of the polytene chromosome banding sequence of non
      biting midje Chironomus pseudothummi str. (Diptera, Chironomidae)].
AB  - The karyotypes and chromosomal polymorphism of Chironomus pseudothummi were
      investigated in different parts of its range. It was established that chromosomal
      variability in the natural populations of this species was represented mainly by
      the inversion polymorphism of arm G. Only rare and unique inversions were found
      as heterozygous in arms C, D, and E. In total, the 14 banding sequences of
      polytene chromosomes form the banding sequences pool of Ch. pseudothummi.
      Geographic differences in distribution of chromosomal banding sequences
      throughout the range were established. The presence of banding sequences pstG1
      and pstG2 is characteristic of European populations. Banding sequence pstG1 was
      completely vanished with simultaneous increase in frequency of pstG2 and
      appearance of new inversion banding sequence pstG3 in Siberian populations. The
      differences in the set of the rare and unique inversions in arms C, D, and E
      between west-European and west-Siberian populations were revealed.

PMID- 18727408
TI  - [Intellectual activity during formation of quantitative concepts in the lower and
      higher monkeys].
AB  - Results of study of formation of quantitative concepts in the lower and higher
      monkey are presented. Various authors used different methods of study of this
      issue. It has been established that not only the higher primates, such as
      chimpanzee and orangutans, but also the lower ones--macaques, capuchins, squirrel
      monkeys--have the "mathematical capabilities". The detailed study of formation of
      quantitative concepts in primates of different levels of phylogenesis allows
      disclosing mechanisms of formation of this function in human.

PMID- 18727409
TI  - [Arginase activity in the frog urinary bladder epithelial cells and its
      involvement in regulation of nitric oxide production].
AB  - The activity of arginase converting arginine into ornithine and urea is of
      particular interest among many factors regulating NO production in the cells. It
      is known that by competing with NO-synthase for common substrate, arginase can
      affect the NO synthesis. In the present work, the properties of arginase from the
      frog Rana temporaria L. urinary bladder epithelial cells possessing the NO
      synthase activity were characterized, and possible contribution of arginase to
      regulation of NO production by epithelial cells was studied. It has been shown
      that the enzyme had the temperature optimum in the range of 55-60 degrees C, K(m)
      for arginine 23 mM, and V(max) about 10 nmol urea/mg protein/min, and its
      activity was effictively inhibited by (S)-(2-boronoethyl)-L-cysteine (BEC), an
      inhibitor of arginase, at concentrations from 10(-6) to 10(-4) M. The comparison
      of arginase activity in various frog tissues revealed the following pattern:
      liver > kidney >> brain > urinary bladder (epithelium) > heart > testis. The
      arginase activity in the isolated urinary bladder epithelial cells was 3 times
      higher than that in the intact urinary bladder. To evaluate the role of arginase
      in the regulation of NO production, epithelial cells were cultivated in the media
      L-15 or 199 containing different amounts of arginine; the concentration of NO2-,
      the stable NO metabolite, was determined in the culture fluid after 18-20 h of
      cells incubation. The vast majority of the produced nitrites are associated with
      the NOS activity, as L-NAME, the NOS-inhibitor, decreased their accumulation by
      77.1% in the L-15 medium and by 80% in 199 medium. BEC (10(-4) M) increased the
      nitrite production by 18.0 % +/- 2.7 in the L-15 medium and by 24.2 +/- 3.5 in
      the 199 medium (p < 0.05). The obtained data indicate a relatively high arginase
      activity in the frog urinary bladder epithelium and its involvement in regulation
      of NO production by epithelial cells.

PMID- 18727410
TI  - [Transmembranous currents of isolated spinal cord neurons of ammocete--larva of
      the lamprey Lampetra fluviatilis].
AB  - The work is carried out with aid of the patch-clamp method in the "whole cell"
      modification. There were studied potential-activated and chemosensitive currents
      of isolated spinal neurons of the lamprey larva--ammocete. The described
      properties of the currents indicate their similarities with those in adult
      lampreys.

PMID- 18727411
TI  - [Effect of static load on motor behavior of the cockroach Periplaneta americana].
AB  - Effect of static load on activity of motor centers controlling motor activity
      (walking flight) was studied in the American cockroach Periplaneta americana L.
      It has been established that under effect of load on the animal body the relative
      excitability of these centers increases. A suggestion is put forward about the
      presence of common neuronal elements in the generator networks providing motor
      acts in the American cockroach; a role of afferent systems in control of
      excitability of locomotor centers functioning in the regime of static load is
      shown.

PMID- 18727412
TI  - [Diencephalo-telencephalic changes of tyrosine hydroxylase in rats and common
      frogs (Rana temporaria) after sleep deprivation].
AB  - Based on sleep deprivation-produced changes of electrographic parameters of the
      wakefulness--sleep cycle (WSC) in rats and common frogs, dynamics of activity of
      tyrosine hydroxylase, the key enzyme of dopamine synthesis, was studied
      immunohistochemically in substantia nigra and nigrostriatal pathway in rats and
      in striatum, paraventricular organ, and extrahypothalamic pathways in frogs.
      There are revealed changes in dynamics of tyrosine hydroxylase in rats and in
      common frogs after the 6-h sleep deprivation and after 2 h of postdeprivation
      sleep. This allows determining the degree of participation of corticostriatal
      neuroregulatory and hypothalamo-pituitary neurosecretory systems and their role
      in regulation of WSC. Possible evolutionary peculiarities of morphofunctional
      differences in homoiothermal and poikilothermal animals are discussed.

PMID- 18727413
TI  - [Change of the neocortex nervous tissue in rat ontogenesis after hypoxia at
      various terms of embryogenesis].
AB  - The performed study has shown that in rats submitted to hypoxia (3 h, 7% O2) at
      the 14th day of embryogenesis (E14) as compared with control animals, density of
      disposition of cells in the brain cortex decreased for the first month of
      postnatal ontogenesis (maximally by 40.8% by P20). In dying neurons, swelling of
      the cell body, lysis of organoids, and disturbance of the cytoplasmic membrane
      intactness were observed. Two waved of neuronal death by the mechanism of caspase
      dependent apoptosis were revealed; the first involved large pyramidal neurons of
      the V layer (P10-20), the second--small pyramidal and non-pyramidal neurons of
      the II--III layers (P20-30). In neuropil of molecular layer, a decrease of the
      mean amount of labile synaptopodin-positive dendrite spines was observed, as
      compared with control. In rats exposed to hypoxia at E18, no changes of cell
      composition and structure of the nervous tissue were found in the studied brain
      cortex areas. Thus, formation of the cortex nervous tissue in postnatal
      ontogenesis of rats submitted to hypoxia at the period of neuroblast
      proliferation-migration is accompanied not only by a change of the cell
      composition of various cortex layers in early ontogenesis, but also by a decrease
      of the number of the synaptopodin-positive spines in molecular layer, the
      decrease being preserved in adult animals.

PMID- 18727414
TI  - [Recovery of instrumental conditional reflexes in rats after pyramidotomy and
      action of bacterial melanin].
AB  - Unilateral pyramidotomy at the bulbar level performed after preliminary
      elaboration of instrumental conditional reflex (ICR) and without its elaboration
      caused hemiparesis of extremities in rats. Next day after this operation a half
      of the operated animals both with elaborated ICE and without its elaboration was
      injected intramuscularly with bacterial melanin solution (170 mg/kg). Comparison
      of terms of recovery of ICR and of a balancing movement of the paralyzed hindleg
      in the operated rats without administration of melanin and with its injection
      showed that in the "melanin" animals the time of posttraumatic rehabilitation was
      much shorter and recovery of movement occurred faster and more completely. It has
      been found that the difference in terms of recovery of rat motor functions in
      this case is due to the protector action of bacterial melanin.

PMID- 18727415
TI  - [Autonomy of spontaneous rhythmogenesis of perivesicular area of cat ureter].
AB  - The work present data indicating no dependence of the pacemaker activity located
      in the zone of junction of cat ureter with urinary bladder on genesis of the main
      perirenal pacemaker. Data are presented on effect of clamping the renal artery
      supplying with blood flow the renal area on rhythmogenesis of the ureter
      perivesicular area. An inhibition of the pacemaker activity of the pyeloureteral
      anasomosis is observed. At the same time, no marked effect on automatism of the
      low organ area is revealed. Data of morphological studies of the vascular bed
      providing blood supply of various ureter areas are presented.

PMID- 18727416
TI  - [Combinations of active striatal neurons connected selectively with certain
      behavioral actions of the monkey Macaca mulatta].
AB  - At present there is widely spread concept of populational coding of information
      by brain neurons; it is based first of all on results of comparison of neuronal
      activity with parameters of the used stimulus. Relation between the neuronal
      activity coding and the observed behavioral actions has been practically not
      studied. In the present work, neuronal impulse activity has been studied in
      groups of 6 neurons recorded in parallel. Distribution of frequencies of the
      presence of cases of excitation of one or several cells has been established to
      differ statistically significantly form the theoretical distribution of the same
      values; this indicates that under real conditions, the appearance of individual
      combinations of active neurons is not random, but is connected to a certain
      degree with conditions of experiment. The selective combinations of neuronal
      activity have revealed to be different at stages of program. This indicates that
      organization of different behavioral actions is associated with activities of
      certain combinations of neurons.

PMID- 18727417
TI  - [Compensatory and antiamnestic effects of heptapeptide Selank in monkeys].
AB  - The work presents results of study of role of heptapeptide Selank--an anxiolytic
      from group of biologically active peptides--in compensation of disturbed psychic
      and homeostatic functions in monkeys. New data have been obtained which indicate
      that an intranasal administration of Selank produces long-term changes of the
      monkeys' behavior disturbed during neurosis: elimination of fear and aggression
      and an increase of orientational-explorative activity as well as facilitation of
      handling reactions and communicational relations. It has been established that on
      the background of the Selank there occurs a long compensation of disturbed
      psychic functions (processes of memory) and of homeostatic parameters. It has
      been shown that unlike the earlier studied neurohormones (thyroliberin and ACTH4
      10), the antistressor Selank effects do not depend on the type of neurotic
      disturbances and have long-term compensatory character. Comparison of the data
      obtained on monkeys with results of similar studies on the more low-organized
      mammals (rodents) allow suggesting that the new peptide preparation Selank is a
      promising agent for correction of various psychoemotional disturbances (alarm-
      and depression-like disorders).

PMID- 18727418
TI  - [Structure of visual pathways in the nervous system of fresh water pulmonary
      molluscs].
AB  - The central nervous system of freshwater pulmonary molluscs Lymnaea stagnalis and
      Planorbarins corneus was stained by the method of neurobiotin retrograde
      transport along optic nerve fibers. In the animals of both species, bodies and
      fibers of stained neurons are found in all ganglia except for the buccal ones.
      Afferent fibers of the optic nerve form a dense sensor neuropil located in a
      small volume of cerebral ganglia. Characteristic groups of neurons sending their
      processes into optic nerves both of ipsi- and of contralateral half of the body
      are described. Revealed among them are neurons of visceral and parietal ganglia,
      which simultaneously innervate both eyes as well as give projections into
      peripheral nerves. It is suggested that these neurons can perform function of
      integration of sensor signals and, on its base, regulate photosensitivity of
      retina as well as activity of peripheral organs. There is established the
      presence of bilateral connections of the mollusc eye with cells of pedal ganglia
      and statocysts, which seems to be the structural basis of manifestation of the
      known behavior forms associated with stimulation of visual inputs of the studied
      gastropod molluscs.

PMID- 18727419
TI  - [Distribution of metabolic activity (cytochrome oxidase) and immunoreactivity to
      calcium-binding proteins in turtle brainstem auditory nuclei].
AB  - Using histochemical and immunohistochemical techniques, distribution of activity
      of oxidative mitochondrial enzyme cytochrome oxidase (CO) and of immunoreactivity
      to calcium-binding proteins has been studied in spiral ganglion and auditory
      nuclei of brainstem in two turtle species. It has been shown that
      immunoreactivity to calbindin, parvalbumin, and calretinin in neurons and
      neuropil of nuclei of cochlear and superior olivary complexes, in nucleus of
      lateral lemniscus, and in spiral ganglion neurons coincides topographically with
      the high CO activity. The similarity of the studied metabolic and neurochemical
      characteristics of these auditory centers in reptiles, birds, and mammals
      indicates the existence of some common principles of their organization in
      amniotes in spite of phylogenetic differences and peculiarities of specialization
      of the auditory system in different species.

PMID- 18727420
TI  - [Effect of apoptosis proteins on function of vasopressin- and dopaminergic
      hypothalamic neurons].
AB  - To study character of effect of apoptosis signal proteins on activities of
      neurosecretory cells and neurons of rat hypothalamus, pharmacologic inhibitors of
      proapoptotic protein p53 Pifithrin-alpha and antiapoptotic protein Bcl-2 HA14-1
      were injected into the hypothalamus. Activation of vasopressinergic
      neurosecretory cells at administration of the blocker Bcl-2 HA14-1 was shown:
      there were observed an increase of vasopressin mRNA in neurons of hypothalamus
      supraoptical and paraventricular nuclei, a decrease of the immunoreactive
      vasopressin content in posterior pituitary, and reduction of diuresis.
      Inactivation of p53 inhibited release of vasopressin from hypothalamus cell
      bodies, which is indicated by an elevated content of immunoreactive vasopressin
      in neurosecretory cell bodies with its unchanged synthesis, a decrease of the
      neurohormone content in the posterior pituitary, and an increase of diuresis
      rate. Activation of vasopressinergic neurons of the suprachiasmatic nucleus was
      also shown. Administration of the blocker Bcl-2 has been revealed to decrease
      functional activity both of dopaminergic neurons (Zona Incerta) and of
      dopaminergic neurosecretory cells (arcuate nucleus), in which a decrease of the
      tyrosine hydroxylase content was observed. The p53 inactivation also led to a
      decrease of activity of dopaminergic neurosecretory cells of arcuate nucleus,
      whereas activity of the proteins Zone Incerta did not change. Thus, it has been
      shown that a change of the apoptotic protein content in vasopressinergic and
      dopaminergic neurons and neurosecretory cells leads to a change of their
      functional activity, the character and possibly mechanisms of effects of
      apoptotic proteins on activities of vasopressin- and dopaminergic cells being
      different.

PMID- 18727421
TI  - [Dependence of sodium and potassium ion transport across the cell membrane on
      energy metabolism in oocytes of the lamprey Lampetra fluviatilis].

PMID- 18727422
TI  - [Effect of baclofen on ionotropic current produced by glycine application on
      spinal cord neurons of the frog Rana temporaria].

PMID- 18727423
TI  - [Hypersiderosis and dissiderosis in the context of data on hemochromatosis
      microelementosis].
AB  - The review summarizes the results of the state-of-the-art studies of
      hemochromatosis (HC): iron-regulatory genes (HFE, HJV, HAMP, TFR2, SLC40A1) have
      been discovered; the HC types caused by mutations in these genes (types 1, 2, 3,
      and 4 in the OMIM register) have been identified; the inflammation anemia (IA)
      mediator - the polypeptide hepatic hormone hepcidin that is an important
      constituent of the natural immunity system - has been found. This gives an idea
      of hypersiderosis and dissiderosis as types of iron microelementosis. Types 1, 2,
      and 3 HC in which iron absorption and its total reserves are increased in the
      body serve as examples of hypersiderosis. Dissiderosis is characterized by the
      redistribution of iron between the functional and spare funds inherent in type 4
      HC and IA. By taking into account their findings, the authors briefly discuss the
      leading clinical and morphological manifestations of HC and IA, difficulties in
      differential diagnosis, and treatment ways and prospects.

PMID- 18727425
TI  - [Immunohistochemical evaluation of the distribution of vascular endothelial
      growth factor in the placenta, placental bed in normal pregnancy and in women
      with preeclampsia].
AB  - VEGF expression was immunohistochemically studied in 35 placental fragments and
      15 placental bed biopsy specimens in a control group and in 34 placental
      fragments and 16 biopsy specimens in women with preeclampsia. The female serum
      concentrations of VEGF and sFlt-I were measured in both groups. There was a
      drastic reduction in VEGF expression in the placenta (syncytiotrophoblast, free
      symplasts, syncytial kidneys); the placental bed biopsy specimens showed the
      impaired rearrangement of maternal-placental arteries with the lower VEGF
      expression in the cytotrophoblastic cells from women with preeclampsia. The blood
      displayed a 10-fold reduction in VEGF along with a 3.5-fold increase in SFlt-1
      concentrations. Deficiency of free (circulating) VEGF-A that is so essential for
      normal endothelial function is likely to cause its structural changes that are
      united under the term "endotheliosis" as one of the leading mechanisms of the
      pathogenesis of gestosis.

PMID- 18727424
TI  - [Comparative investigations of the determination of the HER-2 status in breast
      cancer by fluorescence and chromogenic in situ hybridization].
AB  - Forty invasive breast ductal carcinoma biopsy specimens were investigated. The
      techniques of fluorescence and chromogenic in situ hybridization were used to
      study HER-2/neu gene amplification and the concordance of these techniques was
      examined. The advantages and disadvantages of both techniques are shown. The
      optimum ranges of using these techniques in the determination of the herzept
      status of breast cancer are given.

PMID- 18727426
TI  - [Significance of the expression of nucleolar argyrophilic proteins and antigen Ki
      67 in the evaluation of cell proliferative activity and in the prediction of
      minimal (T1) lung cancer].
AB  - S u m m a ry. - The subject of the study was 20 cases of non-small-cell lung
      carcinomas, up to 3 cm in diameter, conventionally designed as minimal lung
      cancers removed in patients operated on at the N. N. Blokhin Cancer Research
      Centre, Russian Academy of Medical Sciences in 1986 to 2001. According to
      survival rates after surgery, the patients were divided into two groups: 1) those
      who died within the first two years; 2) those who were followed up for 3-5 years.
      Histological, histochemical, and immunohistochemical studies were performed. The
      expression of argyrophylic nucleolar organizer site proteins (Ag-NOS-proteins)
      that characterized the rate of cell proliferation (the duration of a cellular
      cycle) and the expression of Ki-67 antigen, which reflected the fraction of
      growth (the number of proliferating cells), were revealed in the tumor cells.
      Minimal lung cancers were found to be a heterogeneous group of neoplasms showing
      differences in both the rate of cell proliferation and the count of proliferating
      cells. The cell proliferation rate is a determinant of the clinical course of
      minimal lung cancers. Group 1 tumors characterized by the superexpression of Ag
      NOS-proteins and, accordingly, the higher cell proliferation rate and the
      moderate count of proliferating cells had a poor prognosis even in the presence
      of Stage IA whereas Group 2 tumors with a large quantity of proliferating cells,
      but with the less rate of cell proliferation were characterized by a much better
      prognosis. The rate of cell proliferation (expression of Ag-NOS-proteins) and the
      count of proliferating cells (the expression of Ki-67 antigen) should be
      simultaneously studied to have more complete information on the proliferative
      potential of tumor cells and on the prediction of the course of neoplasms.

PMID- 18727427
TI  - [The morphofunctional characteristics of proteins of nucleolar organizers in
      uterine smooth muscle tumors].
AB  - The authors have shown the activity of argyrophylic nucleolar organizer region
      proteins (Ag-NOR-proteins) in the uterine leiomyomas of varying histological
      structure and determined their relationship to the growth rate, size, and site of
      a node and endometrial pathology. The investigation indicat yomas with
      significant sclerosis, 4.32 +/- 0.1 in simple leiomyomas, and 6.2 +/- 0.2 in cell
      leiomyomas (r = 0.58). In menopause, myomas with significant sclerosis and
      hyalinosis were characterized with a small number of Ag-NOR (1.44 +/- 0.04).
      Thus, the organizers numbered 12.1 +/- 0.5 and 21.7 +/- 1.0 in high- and low
      grade sarcomas, respectively, which may be used in the differential diagnosis of
      cellular, bizarre, mitotically active leiomyomas and leiomyosarcomas.

PMID- 18727428
TI  - [Use of postmortem brain magnetic resonance imaging at autopsy].
AB  - The study was undertaken to define the possibilities of using postmortem MRI for
      examining the brain. A complex study was made to explore 21 neutral formalin
      fixed gross brain specimens from patients with neurosurgical pathology.
      Macroscopic and target histological studies of the changed signal areas detected
      by MRI were performed using histochemical stains. The significance of the results
      obtained by MRI in vitro has been defined, which furnish considerable
      opportunities to use the technique for the postmortem diagnosis of various
      diseases, to detect macroscopically undetectable changes (perifocal changes,
      metastases), to make a complex of intractable diagnostic problems, and to study
      the histological substrate of changed MR signal areas.

PMID- 18727429
TI  - [A relationship of congenital brain malformations and tumor growth].
AB  - The peritumor-like areas of 12 cerebral hemispheric tumors were examined.
      Histological study revealed vascular malformations and/or congenital tissue
      dysplasias in all cases: cortical disorganization, neuronal heterotopy into the
      white matter, neural location in the molecular cortical layer, and persistence of
      a subpial granular cell layer. Immunohistochemical study using Ki-67 antibodies
      in the peritumor-like tissue dysplasias revealed proliferative activity in a
      number of cases. The associations of the origin of brain tumors and congenital
      malformations are discussed.

PMID- 18727430
TI  - [Melatonin expression in nasal polyps in patients with asthmatic triad].
AB  - The expression of melatonin in nasal polyps versus the histological structure of
      tissue was studied in 11 patients with aspirin-induced asthma (AIA), 8 patients
      with asthma without aspirin intolerance, 13 patients with polypous
      rhinosinusopathy (PR) without bronchopulmonary diseases, and 10 apparently
      healthy individuals without nasal polyposis. The expression of melatonin in the
      nasal mucosa was found to be normal in healthy individuals. It significantly
      increased in polyp tissue in PR. The specific feature of polyp tissue in patients
      with aspirin triad was its high eosinophils levels that correlated with the
      increased area of melatonin expression. Thus, in AIA patients, the role of
      eosinophils increases in the production and/or delivery of the hormone into polyp
      tissue along with a drastic reduction in platelet melatonin generation. The
      findings explain persistent recurrent PR in AIA patients and an exacerbation of
      the disease after polyp removal.

PMID- 18727431
TI  - [Morphological study of the mechanisms of osteointegration of intraosseal
      titanium implants].
AB  - The present study was undertaken to work out a new material based on titanium
      coated polytetrafluoroethylene, which would have the integration potential
      similar to that of titanium implants, which would make it possible to use it as a
      model to study osseointegration processes. Rat experiments compared titanium
      implants and a combined model of a titanium-nanocoated polytetrafluoroethylene.
      The present study has indicated that the new experimental model of the implant
      opens the door to in-depth investigations of a peri-implant bone regeneration
      area.

PMID- 18727432
TI  - [Analysis of the heterogenicity of cytological and morphometric indices of the
      endothelial nuclei of the aorta and pulmonary artery in atherosclerosis].
AB  - The authors made a qualitative cytological analysis of the percentage of the
      heterogenic endothelium and its association with the severity of atherosclerosis.
      A total of 15,000 endotheliocytes (usual-type, giant uninucleated, binucleated,
      trinucleated, multinucleated, and horseshoe-shaped nuclei) were studied above
      different forms of atherosclerotic lesion of the human aorta and pulmonary
      artery. The material was obtained from 5 deceased patients aged 35 to 85 years.
      Both uninucleated and multinucleated cells were identified as the endothelium by
      an immunohistochemical test in the detection of specific factor VIII antigen in
      their cytoplasm. The proportion of heterogenic cells above the intact portions of
      the pulmonary artery and aorta was ascertained to be 13.7 and 24.8%,
      respectively; at the same time that of this endothelium above the fatty streaks
      increased up to 56.1 and 58.7%, respectively; and that above fatty plaques did up
      to 72.2 and 73.1%, respectively. Thus, the total number of endotheliocytes with
      the usual type of nuclei statistically significantly decreased above
      atherosclerotic lesions (fatty streaks and plaques) of the pulmonary artery and
      aorta to 35.8 and 31.8%, respectively. Extrusion of a population of cells with
      the usual type of nuclei with the progress of atherosclerotic lesions is attended
      by an increase in the proportion of the heterogenic endothelium up to 64.2 and
      68.2%, respectively. It is suggested that the optimum combination of variable
      dimensions of the endothelium and the size and number of their nuclei is an
      adaptive reaction and an essential prerequisite to the most effective endothelial
      function when atherosclerotic lesion of the arterial intima progresses.

PMID- 18727433
TI  - [Low-intensity laser irradiation-induced rat breast morphological changes].
AB  - [The paper presents the characteristics of breast parenchyma and stromal
      morphological changes in non-inbred albino rats exposed to various low-intensity
      laser irradiation modes]

PMID- 18727434
TI  - [Mesenchymal chondrosarcoma of the lung].
AB  - The authors present the data available in the literature and their observation of
      mesenchymal chondrosarcoma of the lung a 68-year-old female patient.
      Histologically, the tumor is exhibited by the fields of monomorphic round and
      oval cells with hyperchromic muclei and a scanty cytoplasm, with the
      hemangiopericytoma-like structures being formed here and there. There are foci of
      chondroid cells, portions of necrosis, and an ample quantity of mitoses.
      Immunohistochemical study has revealed that the tumor cells show the expression
      of vimentin, S-100 protein, neuron-specific enolase and the cytoplasmic
      expression of CD 99. The tests using CD 31, CD 34, factor VIII, desmin, total
      cytokeratin, or synaptophysin are negative.

PMID- 18727435
TI  - [Appendicular metastatic involvement in breast cancer].
AB  - The paper describes a case of appendicular metastatic involvement in breast
      cancer. The 60-year-old female patient developed the signs of acute appendicitis
      18 years after detection of primary tumor; after appendectomy the intraoperative
      appendular specimens exhibited trains of tumor cells that infiltrated the mid-
      and lower muscle layer third. Immunohistochemical study revealed a moderate
      expression of Er and Pgr receptors (150 H scores), a positive reaction with EMA,
      K7, K6, and lactoalbumin The authors review the data available in the literature
      on the specific features of metastatic spread into the appendix and on management
      tactics in these patients.

PMID- 18727436
TI  - [Congenital neuroblastoma].
AB  - The paper describes a clinicoanatomic case of congenital neuroblastoma of various
      differentiation degree in a boy aged 1 year and 9 months after 4 courses of up-to
      date multidrug therapy.

PMID- 18727437
TI  - Rhabdomyosarcoma an ubiquitous pediatric tumour.
AB  - Rhabdomyosarcoma is the most common soft tissue tumor in children. It occurs
      everywhere and its prognosis depends on the location and its histological type-
      embryonic or alveolar. The new immunohistochemical markers desmin and myogenin in
      combination with molecular biological detection of specific translocations in
      alveolar rhabdomyosarcoma improved diagnostic capacities. Less aggressive
      treatment in curable cases reduces the undesirable outcomes of therapy.

PMID- 18727438
TI  - [Gastroesophageal reflux disease: pathogenesis and morbid anatomy].
AB  - By analyzing the current data available in the literature, the authors consider
      the pathogenesis and morbid anatomy of gastroesophageal reflux disease. They
      assess the role of the anatomic and physiological features of the esophagogastric
      transition in the development of reflux-esophagitis and its complications. The
      principles of morphological diagnosis are considered in the interpretation of
      esophageal biopsy in reflux-esophagitis and Barrett's esophagus.

PMID- 18727439
TI  - Antiviral Chemistry & Chemotherapy's current antiviral agents FactFile (2nd
      edition).

PMID- 18727440
TI  - Antiviral Chemistry & Chemotherapy's current antiviral agents FactFile (2nd
      edition): DNA viruses.
AB  - Although most of the recent attempts to develop new antiviral agents have been
      focussed on RNA viruses (in particular, HIV and hepatitis C virus), a few new
      compounds are now awaiting their entry into the field of DNA viruses,
      particularly poxviruses, such as variola virus, because of the bioterrorist
      context, and herpesviruses, such as herpes simplex virus and cytomegalovirus,
      where the market scene has for many years been dominated by acyclovir,
      penciclovir and ganciclovir and their respective orally bioavailable prodrugs:
      valaciclovir, famciclovir and valganciclovir. Here, we review the current 'state
      of the art' with old compounds ready to rotate off and new compounds eagerly
      awaiting to appear on the continuously evolving scene of antiviral drug
      development.

PMID- 18727441
TI  - Antiviral Chemistry & Chemotherapy's current antiviral agents FactFile 2008 (2nd
      edition): RNA viruses.
AB  - Among the RNA viruses, other than the retroviruses (that is, HIV), which are
      dealt with separately in the current FactFile, the most important targets for the
      development of antiviral agents at the moment are the orthomyxoviruses (that is,
      influenza), the hepaciviruses (that is, hepatitis C virus [HCV]) and, to a lesser
      extent, the picornaviruses. Although the uncoating inhibitors amantadine and
      rimantadine were the first known inhibitors of influenza A, the neuraminidase
      inhibitors oseltamivir, zanamivir and peramivir have now become the prime
      antiviral drugs for the treatment of influenza A and B virus infections. For HCV
      infections, standard treatment consists of the combination of pegylated
      interferon-alpha with ribavirin, but several other antivirals targeted at
      specific viral functions such as the HCV protease and/ or polymerase may be
      expected to soon take an important share of this important market. Still untapped
      is the potential of a variety of uncoating inhibitors, as well as protease and/or
      polymerase inhibitors against the wide spectrum of picornaviruses. While
      ribavirin has been available for 35 years as a broad-spectrum anti-RNA virus
      agent, relatively new and unexplored is favipiravir (T-705) accredited with
      activity against influenza as well as flaviviruses, bunyaviruses and
      arenaviruses.

PMID- 18727442
TI  - Antiviral Chemistry & Chemotherapy's current antiviral agents FactFile (2nd
      edition): retroviruses and hepadnaviruses.
AB  - There are at present exactly 25 compounds that have been formally approved for
      the treatment of retrovirus (that is HIV) infections: seven nucleoside reverse
      transcriptase inhibitors (NRTIs), one nucleotide reverse transcriptase inhibitor
      (NtRTI), four non-nucleoside reverse transcriptase inhibitors (NNRTIs), 10
      protease inhibitors (PIs), one coreceptor inhibitor (CRI), one fusion inhibitor
      (FI) and one integrase inhibitor (INI). Other compounds expected to be approved
      for the treatment of HIV infections in the near future are the NNRTI rilpivirine,
      the CRI vicriviroc and the INI elvitegravir. To obtain synergistic activity,
      enable lower dosage levels, thus minimizing toxic side effects, and particularly
      to reduce the risk of drug resistance development, common wisdom dictates that
      the HIV inhibitors should be used in drug combination regimens. Although, given
      the number of compounds available, the drug combinations that could be concocted
      are uncountable, only one triple-drug combination has so far been formulated as
      single pill to be taken orally once daily, namely Atripla containing the NtRTI
      tenofovir disoproxil fumarate, the NRTI emtricitabine and the NNRTI efavirenz.
      Here, we document these approved compounds along with other HIV-active compounds
      and, for the first time, compounds whose principal activity is against hepatitis
      B virus. The logic of this new division being the enzymatic similarity between
      the reverse transcriptase of HIV and hepatitis B virus; the strategies for the
      development of antiviral agents to combat them have much in common.

PMID- 18727443
TI  - What do patient satisfaction, safety and malpractice risk have in common?

PMID- 18727444
TI  - DEA releases proposed rule for e-prescribing controlled substances.

PMID- 18727446
TI  - Prepare now for lots of new diagnosis codes.

PMID- 18727445
TI  - The more you know.

PMID- 18727447
TI  - Fraud squad Rx.

PMID- 18727448
TI  - Managing your practice's relationships with legal counsel.

PMID- 18727449
TI  - Turning down the heat. Don't let inappropriate office relationships put your
      practice at risk.
AB  - When a married physician partner had an affair with a married staff member, the
      practice administrator stepped in before the situation boiled over.

PMID- 18727450
TI  - Keep your patients coming back.
AB  - Does your practice deliver the customer service--in addition to the medical care-
      that patients want? The secrets of engaging physicians in a better patient
      experience.

PMID- 18727451
TI  - Doing well by doing good. The 7 benefits of a meaningful corporate social
      responsibility program.
AB  - You want your medical group to be a good community player--but you need to
      attract new patients, retain top staff and manage your bottom line. A corporate
      social responsibility program may be the shrewd solution.

PMID- 18727452
TI  - Kindermusik educator Valerie Loudenback, clinic manager, Hegg Memorial Health
      Center Avera, Rock Valley, Iowa.

PMID- 18727453
TI  - Effects of therapeutic doses of Pregabalin on QTc interval in conscious rabbits.
AB  - Pregabalin (PRG) is a new antiepileptic drug that has been used as supportive
      therapy for partial seizures in patients. Although many neuro-psychiatric and non
      cardiac drugs are known to prolong ventricular repolarization as manifested by
      QTc prolongation on ECG of which provokes torsades de pointes, there is limited
      data available regarding the characteristics of QT interval in conscious
      laboratory animals after PRG administration. For that purpose, effects of
      different therapeutic doses of oral PRG administration on Heart Rate (HR), QT and
      QTc values in rabbits were evaluated at a predefined time interval in this
      research. The study involved 28 New Zealand rabbits of both sexes, aged between 8
      and 12 months. Animals were divided into four equal groups. Rabbits in control
      group (CG) received saline 0.5 ml/per animal orally. Group I, II and III were
      orally given single dose of PRG at 1.25 mg/kg, 2.5 mg/kg and 5 mg/kg,
      respectively. ECG records were taken before experiment (baseline) and at 1st,
      2nd, 4th, and 6th hour (h) of experiment by direct writing electrocardiograph.
      HR, QT and QTc values were determined from ECG records. Heart rates increased in
      all groups when compared to baseline values. The increases were evident at 4th h
      in group II (p < 0.001), at 2nd h (p < 0.05) and 4th h (p < 0.001) in group III
      compared with CG. After application of PRG, QTc began to prolong at 1st h through
      the 4th of experiment and then turned to baseline values at 6th h of the
      experiment. The QTc values obtained at 2nd h in Group II and III (p < 0.05) and
      4th h (p < 0.001) of application in group III were significantly different from
      CG. Changes obtained in HR, QT and QTc values in PRG treated rabbits were time
      and dose dependent (p < 0.001). Increase in HR and QTc prolongation determined in
      PRG given rabbits may implied that clinicians should take care of these changes
      when using this drug and further studies are required to fully understand the
      mechanism involved.

PMID- 18727454
TI  - Efficacy and safety of eperisone in patients with low back pain: a double blind
      randomized study.
AB  - Eperisone hydrochloride (4'-ethyl-2-methyl-3-piperidinopropiophenone
      hydrochloride) is an antispastic agent used for treatment of diseases
      characterized by muscle stiffness and pain. The aim of this research was to
      investigate the efficacy of eperisone in patients with acute low back pain and
      spasticity of spinal muscles. The study design was a randomized, double-blind
      (double-dummy) study in 160 patients with low back pain and no Rx finding of
      major spinal diseases, randomly assigned to a treatment with oral eperisone 100
      mg three times daily (t.i.d.) or thiocolchicoside 8 mg twice daily (b.i.d.) for
      12 consecutive days. Analgesic activity was evaluated by scoring "spontaneous
      pain" (VAS) and pain on movement and pression (4-digit scale), while muscle
      relaxant activity of the medication was evaluated by means of the "hand-to-floor"
      distance and the Lasegue's manoeuvre. All the measures were done at the inclusion
      day and after 3, 7 and 12 days of treatment. The two medications had comparable
      analgesic and muscle relaxant efficacy. Sponta-neous pain and pain on
      movement/pressure were significantly reduced by both treatments. Moreover, both
      eperisone- and thiocolchicoside-treated patients showed a clinically evident
      muscle relaxation as proved by a progressive reduction in the "hand-to-floor"
      distance and increase in the articular excursion (Lasegue's manoeuvre). Only 5%
      of eperisone-treated patients showed minor gastrointestinal side effects, while
      the incidence of side effects in the thiocolchicoside group was 21.25%. Moreover,
      in the thiocolchicoside-treated patients also diarrhoea was present, which
      reached a moderate intensity in some cases. In conclusions, eperisone represents
      a valuable and safer alternative to other muscle relaxant agents for treatment of
      low back pain.

PMID- 18727455
TI  - Effect of earthworm powder on antioxidant enzymes in alcohol induced hepatotoxic
      rats.
AB  - Earthworms have been widely used in traditional medicine for thousands of years.
      However, it is only during the past few decades, with the development of
      biochemical technologies, that research on the pharmaceutical effects has been
      initiated. The present study was carried out to investigate the hepatoprotective
      and antioxidant properties of indigenous earthworm powder (Perionyx excavatus),
      using alcohol induction as a model of hepatotoxic and oxidative damage. Alcohol
      hepatotoxic rats exhibited elevation in the lipid-peroxidative marker
      thiobarbituric acid reactive substance (TBARS). A decrease in the activities of
      enzymatic antioxidant enzymes: Superoxide dismutase (SOD), Catalase (CAT),
      Glutathione peroxidase (GPx), and non-enzymatic antioxidant vitamin C, vitamin E
      and reduced glutathione (GSH) was observed. Oral administration of dried
      earthworm powder (500 mg/kg body weight) for 42 days reversed these parameters
      towards normalcy. These results suggest that the indigenous earthworm Perionyx
      excavatus could afford a significant hepatoprotective and antioxidant effect
      against alcohol induced rats.

PMID- 18727456
TI  - 13C-methionine breath tests for mitochondrial liver function assessment.
AB  - 13C-methionine breath test has been proposed as a non-invasive tool for the
      assessment of human hepatic mithocondrial function. Two methionine breath labeled
      with 13C in differents point of his molecular structure have been used for breath
      test analisys. Aim of this study was to compare two differently 13C-labeled
      methionines in the evaluation of mitochondrial oxidation in basal conditions and
      after an acute oxidative stress. 15 healthy male subjects (mean age 30.5 +/- 3.1)
      received [methyl-13C]-methionine dissolved in water. Breath samples were taken at
      baseline and and 10, 20, 30, 45, 60, 75, 90, 105 and 120 minutes after the
      ingestion of the labeled substrate. Forthy-eight hours later, subjects underwent
      the same test 30 minutes after ethanol ingestion (0,3 g/kg of body weight). Seven
      day later, subjects underwent breath test using (L-methionine-1-13COOH) as
      substrate, in basal condition and after ethanol ingestion. At basal condition,
      the cumulative percentage of 13CO2 recovered in breath during the test period
      (%cum-dose) was higher using L-methionine-1-13COOH than [methyl-13C]-methionine
      (10.25 +/- 1.0 vs 4.07 +/- 0.8; p < 0.01). After ethanol ingestion, % cum dose
      was significantly decreased at 60 and 120 minutes with both methionines (120 min:
      10.25 +/- 1.0 vs 5.03% +/- 1.8; < 0.01 and 4.07 +/- 0.8 vs 2.16% +/- 0.9; p <
      0.01, respectively). However, %cum-dose during L-methionine-1-13C-breath test was
      significantly lower than that observed during methyl-13C-methionine breath test
      (120 minutes: 5.03% +/- 1.8 vs 2.16% +/- 0.9; p < 0.01). In conclusion, breath
      test based on L-methionine-1-13COOH seems to show a greater reliability when
      compared to [methyl-13C]-methionine to assess mitochondrial function because a
      larger amount of labeled carbon that reaches the Krebs' cicle.

PMID- 18727457
TI  - Triple therapies plus different probiotics for Helicobacter pylori eradication.
AB  - The Helicobacter pylori (H. pylori) cure rate following standard triple therapies
      is decreasing worldwide. Therefore, further approaches aimed to improve standard
      triple therapy efficacy should be attempted. This prospective, pilot study aimed
      to evaluate the therapeutic role of either Lactobacillus reuteri (L. reuteri) or
      a high concentration of probiotics in addition to standard triple therapies for
      H. pylori eradication. The study enrolled 65 consecutive dyspeptic patients with
      H. pylori infection. All patients underwent upper endoscopy with gastric
      biopsies. Patients were assigned to receive one of the following therapies: (a)
      standard 7-day triple; (b) the same 7-day triple therapy plus L. reuteri
      supplementation; (c) the same 7-day triple therapy plus a probiotic mixture; and
      d) a 14-day standard triple therapy plus a probiotic mixture. H. pylori
      eradication was checked by using a 13C-urea breath test performed 4-6 weeks after
      treatment. No therapy regimen achieved > 80% eradication rate at both intention
      to-treat (ITT) and per protocol (PP) analyses. Although the 14-day therapy plus a
      probiotic mixture tended to achieve higher eradication rate (71%), no
      statistically significant difference emerged among the different therapy regimens
      tested (range: 53-71%). The lowest incidence of side-effects was observed
      following the 7-day therapy plus L. reuteri (6%) and highest with the 14-day
      triple therapy plus probiotic mixture (33%), although the difference failed to
      reach the statistically significance. In conclusion, our data found that 7-14
      days triple therapy with or without probiotic supplementation failed to achieved
      acceptable H. pylori eradication rates.

PMID- 18727458
TI  - Retrospective survey on laparoscopic cholecystectomy in the cirrhotic patient.
AB  - Cholelitiasis is a common disease in patients with liver cirrhosis, mainly due to
      intravascular haemolysis and functional alterations of the gallbladder. In Child
      A and B cirrhotics laparoscopic cholecystectomy (LC) demonstrated the same
      advantages and safety as in the non cirrhotic patients. On the contrary,
      indications for surgery in Child C patients should be carefully evaluated.
      Nevertheless, the current number of patients with Child C cirrhosis submitted to
      LC is too low to extrapolate definitive data. Here we report our observations on
      a retrospective case series of LCs performed for symptomatic biliary disease in
      patients affected with liver cirrhosis. Both medical records and surgical
      registers were used to collect pre-operative, intra-operative and post-operative
      data from 40 cirrhotics out of 921 patients operated by laparoscopic
      cholecystectomy between November 1996 and November 2006. All patients underwent
      LC because of symptomatic disease. The average duration of the laparoscopic
      intervention was 111 minutes (60-220 minutes) distributed as follows according to
      the severity of liver disease: 66 minutes (48-87) in the Child A group, 108
      minutes (91-119) in the Child B group and 138 minutes (110-160) as refers to
      Child C cirrhotics. Median blood loss was quantified as 80 ml (28-97) in Child A
      group, 155 ml (130-180) in Child B group and 300 ml (220-500) among Child C
      cirrhotics. The median length of hospital stay was 6 days (3-9 days) in the Child
      A group, 9 days (7-13 days) in the Child B group and 21 days (16-27 days) in
      Child C cirrhotics. Three cases out of 40 (7,5%) died: 2 Child C and 1 Child B.
      In conclusion, this study confirms that in patients affected with Child A and B
      cirrhosis LC may be safely performed either in emergency or in election whereas
      as refers to Child C cases we have observed a slightly higher mortality but a
      relevant higher impact of non lethal complications.

PMID- 18727459
TI  - A randomized clinical trial with two enteral diabetes-specific supplements in
      patients with diabetes mellitus type 2: metabolic effects.
AB  - The aim of this study was to investigate whether two specific diabetes enteral
      formulas could improve nutritional as well as metabolic parameters in elderly
      patients with diabetes mellitus type 2. A population of 30 elderly patients with
      diabetes mellitus type 2 with recent weight loss was recruited. At basal time
      diabetic patients were asked to consume randomly two cans per day of two
      different specially designed high monounsaturated fatty acid diabetes-specific
      supplement: one with 49.95% of calories provided by fats (I), the second with a
      34% of calories provided by fats (II), for a ten week period. A significative
      decrease of glucose (119.8 +/- 42 vs 95.1 +/- 16.8 mg/dl: p < 0.05) and Hbalc
      (8.2 +/- 2.8 vs 5.8 +/- 0.7%: p < 0.05) levels was observed in group I with a
      significant increase in serum albumin levels (3.1 +/- 0.8 vs 3.5 +/- 0.5 g/dl: p
      < 0.05). A significant increase of serum albumin (3.1 +/- 0.4 vs 3.7 +/- 0.6
      g/dl: p < 0.05) and total proteins (6.3 +/- 0.5 vs 6.9 +/- 0.3 g/dl: p < 0.05)
      was observed in group II. Patients of group II had a significant improvement in
      weight (56.5 +/- 16 vs 58.3 +/- 15 kg: p < 0.05), body mass index (21.8 +/- 5.6
      vs 22.5 +/- 5.3 kg/m2: p < 0.05) and fat mass (15.7 +/- 6.4 vs 16.9 +/- 6.2 kg: p
      < 0.05). In conclusion, high monounsaturated fatty acid diabetes-specific enteral
      supplement improved glucose, HbAlc and albumin levels. A diabetes-specific
      supplement with lower fat percentage than the first improved weight and protein
      levels without significative metabolic effects.

PMID- 18727460
TI  - Antinuclear antibodies prevalence in Filipinos migrated to Italy.
AB  - Antinuclear antibodies (ANA) represent the main diagnostic markers for systemic
      autoimmune disease (AD), although their presence can be detected in blood donors.
      The aim of this study was to study ANA prevalence in healthy subjects of
      different racial groups, exposed to the same environmental factors, in order to
      understand the relevance of genetics or environment in determining autoimmunity.
      We enrolled in this study 80 healthy Filipinos (Polynesian), migrated to Italy
      from an average of 15 years, and 60 healthy native Italians (Caucasian) and ANA
      were detected in their sera (at 1:80 screening dilution) through indirect
      immunofluorescence assay. We found a higher prevalence of ANA positivity in
      Filipinos compared to Italians (23.7% vs 8.3%--P = 0.02; OR 3.43; 95% CI 1.2
      9.8), above all in females and elderly, although demographic characteristics,
      clinical history and habits were not significantly different between the two
      groups. These data confirm that ANA positivity is not a rare condition and
      healthy non-Caucasians present a higher prevalence of autoantibodies. This could
      be determined by their autoimmunity-prone immune system or by the exposition to
      infective agents, pollution, drugs or nutrition of a western country. Future
      studies to evaluate the ANA prevalence in Filipinos in their own country and the
      follow-up of positive patients could clarify the real predisposition to AD of
      this population.

PMID- 18727461
TI  - The endovascular treatment of traumatic isthmic aortic rupture: three years
      follow-up.
AB  - The isthmic aortic rupture represents the main cause of death in car crash
      accidents, because of closed chest trauma. Early medical and surgical care and
      endovascular prosthesis treatment with semi-invasive method can improve short and
      mid term survival. Nine patients with traumatic isthmic aortic rupture underwent
      endoprosthesis aortic implantation. All the patients were male, mean age 42.48 +/
      17.66 years. Operations included 5 acute cases and 4 chronic cases (chance
      diagnosis). In all cases the diagnosis was performed by tomodensitometric exam.
      Cloth prostheses were used (self-expansible Goretex- or Dacron-stent). Three
      years after the endoprosthesis implantation, we obtained the complete thrombosis
      of the false aortic lumen in all patients, both acute and chronic, as well as the
      levelling of the false aneurysms without complications of any kind.

PMID- 18727462
TI  - A suitable test for identifying high risk adult patients of moderate-severe
      obstructive sleep apnea syndrome.
AB  - The aim of this study was the evaluation of the usefulness of a 7-items
      questionnaire, Rome Questionnaire (RQ), in identifying adult patients at risk of
      obstructive sleep apnoea syndrome (OSAS). 136 adults (76 M, 60 F) with snoring
      were enrolled. Each patient underwent to an overnight polysomnography (PSG) study
      and the patient's bed partner answered the "RQ". RQ survey items mainly addressed
      the presence and frequency of snoring behaviour, breathing pauses, sore throat,
      oral breathing and wake time sleepiness. Of the 136 initial patients, 111 (63 M,
      48 F; mean age 54.6 +/- 10.84) with a complete PSG examination were included in
      the study. They were divided according to apnea-hypopnea index (AHI) into two
      groups: group A with a primary snoring or mild OSAS (AHI < or = 15) and group B
      with moderate-severe OSAS (AHI > 15). The RQ final score was 25.27 +/- 16.1 for
      group A and 42.29 +/- 15.2 for group B, with a statistically significant (p <
      0.0001) difference. Analyzing the RQ score of group B (moderate-severe OSAS) we
      surprisingly noticed that most of patients (66%) showed an high RQ score (> 40).
      No patients with moderate-severe OSAS showed a RQ score < 20 and for every point
      scored in the questionnaire there is an extra 1.07 (0.7%) risk of belonging to
      group B. Group B showed a mean body mass index (BMI) of 31.53 (+/- 4.95),
      significantly (p < 0.001) higher than BMI of group A (26,86 +/- 3.28) and BMI
      results a good predictive factor (p = 0.013) of mild-severe OSAS. In conclusion,
      the "RQ", together with BMI, seems to be an useful tool to make a selection of
      the patients at higher risk of moderate-severe OSAS, who need a prompt PSG
      evaluation. Our findings will require further validation in larger sample of
      subjects.

PMID- 18727463
TI  - Acacia dealbata.

PMID- 18727464
TI  - Are breastfeeding and diet strategies overrated for the prevention of atopy?

PMID- 18727465
TI  - Subcutaneous immunoglobulin replacement therapy for primary antibody deficiency:
      advancements into the 21st century.
AB  - OBJECTIVES: To provide a review of the world literature and discuss the clinical
      role of subcutaneous immunoglobulin (SCIG) therapy for primary antibody
      deficiency. DATA SOURCES: English-language publications on SCIG therapy were
      identified through MEDLINE and through the reference list of the initially
      identified publications. STUDY SELECTION: Articles pertaining to SCIG for the
      treatment of immunodeficiency, particularly primary antibody deficiency, were
      selected. RESULTS: SCIG therapy has been shown to be effective and safe for the
      treatment of primary immunodeficiency. The risk of systemic reactions during
      infusion is generally reported to be less than 1%. Many patients prefer SCIG over
      conventional intravenous immunoglobulin therapy because of increased convenience
      and independence associated with SCIG therapy. Publications show SCIG therapy to
      be advantageous in selected patient populations, such as children, pregnant
      women, and patients with poor intravenous access. CONCLUSION: SCIG therapy has
      been widely used in some European countries for a number of years, but a Food and
      Drug Administration-approved product was only recently introduced into the United
      States in 2006. SCIG therapy offers unique advantages that are applicable to many
      patients receiving immunoglobulin therapy for primary immunodeficiency.

PMID- 18727466
TI  - Discrepancy between clinical asthma control assessment tools and fractional
      exhaled nitric oxide.
AB  - BACKGROUND: Asthma is an inflammatory disease, yet clinical tools that evaluate
      asthma control do not include measures of inflammation. OBJECTIVE: To determine
      the correlation between fractional exhaled nitric oxide (FeNO) and each of 5
      asthma control evaluation tools, namely, the Asthma Control Questionnaire (ACQ),
      the Asthma Control Test (ACT), the National Asthma Education and Prevention
      Program (NAEPP) goals of therapy, the Joint Task Force Practice Parameter (JTFPP)
      on attaining optimal asthma control, and the Global Initiative for Asthma (GINA)
      guidelines. METHODS: Patients 6 years or older who had asthma were clinically
      evaluated by an asthma specialist. Patients completed the ACT and ACQ and
      underwent spirometry and FeNO measurement. The physician was blinded to FeNO
      results until asthma control assessments were concluded. Correlations between
      FeNO level and each clinical evaluation tool were calculated. RESULTS: One
      hundred patients 6 to 86 years old were enrolled. No significant association was
      found between FeNO level and asthma control based on ACQ (P > .99), ACT (P =
      .53), NAEPP (P = .53), JTFPP (P = .30), or GINA (P = .86) criteria. Agreement was
      high among the NAEPP, the JTFPP, and GINA; moderate between the ACQ and the ACT;
      and poor to fair between the ACT or the ACQ and the other 3 tools. CONCLUSIONS:
      In addition to clinical evaluation, the incorporation of FeNO measurement in
      evaluating asthma is likely to lead to a more optimal pharmacotherapy, guidance
      in adjusting the dosage of anti-inflammatory agents, and positive long-term
      disease outcome.

PMID- 18727467
TI  - Risk factors for death in adults with severe asthma.
AB  - BACKGROUND: Mortality risk in adult asthma is poorly understood, especially the
      interplay among race, disease severity, and health care access. OBJECTIVE: To
      examine mortality risk factors in adult asthma. METHODS: In a prospective cohort
      study of 865 adults with severe asthma in a closed-panel managed care
      organization, we used structured interviews to evaluate baseline
      sociodemographics, asthma history, and health status. Patients were followed up
      until death or the end of the study (mean, 2 years). We used Cox proportional
      hazards regression to evaluate the impact of sociodemographics, cigarette
      smoking, and validated measures of perceived asthma control, physical health
      status, and severity of asthma on the risk of death. RESULTS: We confirmed 123
      deaths (mortality rate, 6.7 per 100 person-years). In an analysis adjusted for
      sociodemographics and tobacco history, higher severity-of-asthma scores (hazard
      ratio [HR], 1.11 per 0.5-SD increase in severity-of-asthma score; 95% confidence
      interval [CI], 1.01-1.23) and lower perceived asthma control scores (HR, 0.91 per
      0.5-SD increase in perceived asthma control score; 95% CI, 0.83-0.99) were each
      associated with risk of all-cause mortality. In the same adjusted analysis,
      African American race was not associated with increased mortality risk relative
      to white race (HR, 0.64; 95% CI, 0.36-1.14). CONCLUSIONS: In a large managed care
      organization in which access to care is unlikely to vary widely, greater severity
      of-asthma scores and poorer perceived asthma control scores are each associated
      with increased mortality risk in adults with severe asthma, but African American
      patients are not at increased risk for death relative to white patients.

PMID- 18727468
TI  - Asthma control during pregnancy and the risk of preterm delivery or impaired
      fetal growth.
AB  - BACKGROUND: Concerns regarding potential harmful effect of medications on fetuses
      often result in inadequate treatment of asthma in pregnancy, whereas risks posed
      by poorly controlled maternal asthma are often underestimated. OBJECTIVE: To
      evaluate the effect of maternal asthma on preterm delivery and fetal growth.
      METHODS: Study participants were individuals enrolled in the Organization of
      Teratology Information Specialists Asthma Medications in Pregnancy Study between
      February 1, 1998, and December 31, 2003. Pregnant women with physician-diagnosed
      asthma (n = 719) evaluated their asthma control repeatedly during pregnancy based
      on symptom frequency and interference with daily activities and sleep and
      reported hospitalizations and unscheduled clinic visits for asthma exacerbations.
      The incidence of preterm delivery, the incidence of intrauterine growth
      restriction, and mean birth weight were evaluated relative to asthma symptom
      control and exacerbation measures. RESULTS: The incidence of preterm delivery was
      significantly higher among patients with inadequate asthma symptom control during
      the first part of pregnancy (11.4%) compared with patients with adequate asthma
      control (6.3%; P = .02). Similarly, patients who were hospitalized for asthma
      during pregnancy had a higher incidence of preterm delivery (16.4%) compared with
      asthmatic women without a history of hospitalization (7.6%; P = .02). The effect
      seemed independent from use of systemic corticosteroids and other covariates.
      Neither the incidence of intrauterine growth restriction nor mean birth weight
      varied by any measures of asthma symptom control or exacerbations. CONCLUSIONS:
      This study demonstrates a substantial risk for preterm delivery posed by poorly
      controlled maternal asthma and provides additional evidence regarding the
      importance of adequate treatment of asthma in pregnancy to maintain optimal
      asthma control.

PMID- 18727469
TI  - Asthma control and future asthma-related morbidity in inner-city asthmatic
      children.
AB  - BACKGROUND: Asthma guidelines recommend routine evaluation of asthma control,
      which includes measurements of impairment and risk. It is unclear whether
      rigorous asthma control changes risk of asthma morbidity. OBJECTIVE: To examine
      whether the degree of asthma control in inner-city asthmatic children results in
      differential risk reduction of future asthma-related morbidity. METHODS: This
      retrospective observational study examines 960 inner-city children with asthma
      who were highly engaged in an asthma-specific disease management program for a
      minimum of 2 years. Degree of asthma control was determined during the first year
      of enrollment and was categorized as well controlled (> or = 80% of visits in
      control), moderately controlled (50%-79% of visits in control), or difficult to
      control (< 50% of visits in control). Risk and probability of asthma-related
      morbidity at each visit were determined during the second year of enrollment and
      included self-reported asthma exacerbations requiring systemic corticosteroid
      rescue and emergency department visits or hospitalizations. RESULTS: Increasing
      the degree of asthma control measured during the first year of enrollment led to
      statistically significant incremental reductions in risk of acute asthma
      exacerbations and emergency department visits or hospitalizations during the
      second year of enrollment. CONCLUSIONS: Achieving and maintaining asthma control
      in inner-city children with asthma results in significant reductions in asthma
      related morbidity. Systematic assessments of asthma control may be useful for
      predicting future risk in children with asthma.

PMID- 18727470
TI  - Breastfeeding and prevalence of allergic diseases in Japanese university
      students.
AB  - BACKGROUND: Although historical support exists for the concept that breastfeeding
      might be protective against allergic diseases, contradictory findings have been
      observed recently. OBJECTIVE: To investigate the cumulative prevalence of
      allergic diseases in Japanese university students and to identify explanatory
      variables including breastfeeding. METHODS: From March 18, 2003, through March
      29, 2005, a total of 9,615 students newly enrolled at the University of Tokyo
      responded to a written questionnaire on allergic diseases. RESULTS: Cumulative
      prevalence of allergic rhinitis, atopic dermatitis, and asthma was 47.2%, 17.4%,
      and 9.3%, respectively. These data were closely correlated, and prevalence of any
      1 of the 3 diseases significantly increased the odds for historical prevalence of
      the other 2 (P < .001). Male sex (odds ratio [OR], 1.5; 95% confidence interval
      [CI], 1.4-1.7) and maternal (OR, 2.2; 95% CI, 2.0-2.5) or paternal (OR, 1.6; 95%
      CI, 1.4-1.8) history of allergic rhinitis were significant correlates of
      increased odds for allergic rhinitis. Maternal (OR, 2.7; 95% CI, 1.6-4.5),
      paternal (OR, 3.8; 95% CI, 2.2-6.6), or sibling (OR, 1.9; 95% CI, 1.5-2.4)
      history of atopic dermatitis was a significant correlate of increased odds for
      atopic dermatitis. As for asthma, maternal (OR, 4.9; 95% CI, 3.0-7.9), paternal
      (OR, 4.0; 95% CI, 2.3-7.0), or sibling (OR, 3.3; 95% CI, 2.4-4.5) history of
      asthma was a significant correlate of increased odds. Logistic regression
      analysis showed no consistent evidence of the effects of breastfeeding on the
      cumulative prevalence. CONCLUSION: The cumulative prevalence of these diseases
      among young adults revealed that the effect of breastfeeding is negligible when
      compared with genetic factors.

PMID- 18727471
TI  - Evaluation of a group intervention for children with food allergy and their
      parents.
AB  - BACKGROUND: Children with food allergy and their parents may experience
      substantial stress related to the risk of serious reactions and the demands of
      allergy management. OBJECTIVE: To evaluate a group intervention for children with
      food allergy and their parents designed to increase parent-perceived competence
      in coping with food allergy and to decrease the parent-perceived burden
      associated with food allergy. METHODS: Sixty-one children aged 5 to 7 years with
      food allergy and their parents attended 1 of 4 half-day workshops, with parent
      and child groups run concurrently. Parents completed self-report measures of
      perceived competence in coping with food allergy at 3 time points: preworkshop
      (within 8 weeks of the intervention), postworkshop (immediately after the
      intervention), and follow-up (4-8 weeks after the intervention). Parents
      completed a measure of burden associated with food allergy at preworkshop and
      follow-up. Parents and children also completed evaluations of the study
      intervention. RESULTS: Parent-perceived competence in coping with food allergy
      increased significantly from preworkshop to postworkshop and follow-up, and
      parent-perceived burden associated with food allergy decreased from preworkshop
      to follow-up. Parent and child evaluations of the workshop were favorable.
      CONCLUSIONS: These findings provide preliminary support for the effectiveness and
      feasibility of a group intervention for children with food allergy and their
      parents and suggest the importance of controlled evaluations of group
      interventions in this population in the future.

PMID- 18727472
TI  - Incremental prognostic factors associated with cow's milk allergy outcomes in
      infant and child referrals: the Milan Cow's Milk Allergy Cohort study.
AB  - BACKGROUND: The prognosis for many children with cow's milk allergy (CMA) is
      remission within 3 years, and the clinical parameters that predict duration of
      disease have not been measured incrementally. OBJECTIVE: To prospectively
      determine prognostic predictors of tolerance in a random cohort of referrals
      using CMA workup outcomes as covariates and tolerance as the status variable in a
      duration model of CMA. METHODS: The 2001-2006 Milan Cow's Milk Allergy Cohort
      (MiCMAC) enrolled children referrals using double-blind, placebo-controlled food
      challenges (DBPCFCs) as study end points (confirmation of CMA; onset of
      tolerance). The Cox regression model was used to analyze all clinical factors
      that contributed to tolerance. Covariates analyzed were skin, gastrointestinal,
      and respiratory symptoms; history and demographics at presentation; age at
      diagnosis and DBPCFC outcomes; sensitization (skin and serum) by cow's milk
      protein fractions; sensitization to other food and inhalant allergens; total IgE
      levels; specific IgE concentrations for cow's milk protein fractions, other
      ingestants, and aeroallergens; and threshold doses at DBPCFC. Sensitization and
      DBPCFC were performed at 6-month intervals. RESULTS: A total of 112 infants were
      enrolled (mean [SD] age, 13.85 [9.84] months), and 59 achieved tolerance (mean
      [SD] age when tolerance was achieved, 27.58 [11.81] months). On univariate
      analysis, asthma and/or rhinitis at presentation was an independent predictor of
      persistence (hazard ratio [HR], 2.19; 95% confidence interval [CI], 1.26-3.82).
      On multivariate analysis, predictors of persistence were a fresh milk wheal
      diameter increment of 1 mm (HR, 1.18; 95% CI, 1.07-1.31) and a positive skin
      prick test result with soy (HR, 6.99; 95% CI, 1.56-31.25). CONCLUSIONS: This is
      the first study, to our knowledge, to identify incremental biological predictors
      of delayed tolerance to cow's milk in children that should be integrated into
      DBPCFC schedules for CMA in infants.

PMID- 18727473
TI  - Relationship between the atopy patch test and clinical expression of the disease
      in children with atopic eczema/dermatitis syndrome and respiratory symptoms.
AB  - BACKGROUND: The atopy patch test (APT) may be the only positive skin test result
      in patients with either atopic eczema/ dermatitis syndrome (AEDS) or respiratory
      abnormalities with or without AEDS. OBJECTIVE: To investigate the possible
      significance of APT to dust mite by comparing the positive result to this test
      with that of the skin prick test (SPT) in patients with different
      characteristics. METHODS: A total of 297 individuals (178 boys and 119 girls)
      aged 5 to 221 months (mean [SD] age, 64.5 [42.1] months; median age, 58 months)
      were included in this study. Participants were divided into 4 groups: current
      AEDS, current AEDS and respiratory symptoms, past AEDS and respiratory symptoms,
      and respiratory symptoms with neither current nor past AEDS (control group). All
      the patients underwent SPT and APT using house dust mite extract. RESULTS: In the
      study groups, the rate of positivity was significantly higher for APT, whereas in
      the control group, there were significantly more positive results to SPT (P <
      .001 for both). Multivariate analysis showed that there was a high probability of
      a positive APT result in patients with AEDS (odds ratio [OR], 17.4), with AEDS
      and respiratory disease (OR, 21.9), and with past AEDS and respiratory disease
      (OR, 22.8). CONCLUSIONS: These patients with AEDS showed 2 different patterns of
      allergic response to allergens, one IgE mediated (as evaluated by positive SPT
      results) and the other cell mediated (as evaluated by positive APT results). The
      former seems to follow the so-called atopic march model, and the latter persists
      even after the disappearance of AEDS and is likely to be implicated in the
      pathogenesis of respiratory allergy.

PMID- 18727474
TI  - Clinical features of legume allergy in children from a Mediterranean area.
AB  - BACKGROUND: Lentils, chickpeas, beans, and peas are the most common consumed
      legumes in the Mediterranean area. However, there is little information about
      allergy to these legumes. OBJECTIVES: To describe the clinical features of a
      Spanish pediatric population allergic to legumes (lentils, chickpeas, peas, white
      beans, and peanuts), to evaluate the clinical allergy to several legumes, and to
      determine which legume extract is most appropriate to use in the diagnosis of
      legume allergy by skin tests. METHODS: Fifty-four children with allergic
      reactions after exposure to legumes were studied. The diagnosis of legume allergy
      was confirmed by positive skin prick test results with legume extracts and food
      challenges or a recent convincing history of severe reactions. RESULTS: The onset
      of allergic reactions was at approximately the age of 2 years (median, 22
      months). Skin prick test results were positive for at least 3 legumes in 38
      children (70%). Positive results were more frequent to boiled extracts than to
      raw extracts in children with a positive oral challenge. Allergy to lentil was
      the most frequently diagnosed legume allergy (43 children [80%]), followed by
      allergy to chickpea (32 children [59%]). Oral challenges with more than 1 legume
      (median, 3 legumes) were positive in 37 children (69%). The most frequent induced
      symptoms on challenge were respiratory (rhinitis and/or asthma) and cutaneous.
      CONCLUSION: In this population, lentils and chickpeas are the legumes that cause
      most allergic reactions, clinical allergy to more than 1 legume is common, and
      boiled legume extracts are most appropriate to discriminate between allergic and
      tolerant sensitized children.

PMID- 18727475
TI  - Increasing hospitalizations due to angioedema in the United States.
AB  - BACKGROUND: Angioedema may occur in patients taking angiotensin-converting enzyme
      inhibitors. With the more prevalent use of this class of medications in the
      United States, it is not known whether angioedema hospitalizations have increased
      nationally in recent years. OBJECTIVES: To profile the trends in angioedema
      hospitalizations and to examine associated demographic factors and comorbid
      diseases in the United States. METHODS: A national database of hospitalizations
      in the United States was queried for hospitalizations with a principal diagnosis
      of angioedema and other major acute allergic disorders (anaphylaxis, urticaria,
      and allergy unspecified). Subsequent analysis was performed to determine the
      current angioedema hospitalization trends (1998-2005) and to examine clinical and
      demographic variables that distinguished angioedema from the other allergic
      disease admissions. RESULTS: The angioedema hospitalization rate was 3.3 in
      100,000 in 1998 and rose to 4.0 in 100,000 in 2005. In contrast, the combined
      hospitalization rate for nonangioedema allergic disorders showed an overall
      decline and was exceeded by angioedema hospitalization rates after 2000. African
      American patients had consistently higher hospitalization rates (> or = 2 times)
      for angioedema compared with non-African American patients. Hypertension,
      increasing age, and African American ethnicity were associated with angioedema
      hospitalizations. Twenty-four percent of hospitalizations for angioedema were
      coded for an adverse effect due to cardiovascular or antihypertensive agents.
      CONCLUSIONS: Angioedema has become the dominant allergic disorder that results in
      hospitalization in the United States. Angioedema hospitalizations have a distinct
      epidemiologic pattern that differs from that observed in other atopic disease
      hospitalizations.

PMID- 18727476
TI  - Effects of winter birth season and prenatal cockroach and mouse allergen exposure
      on indoor allergen-specific cord blood mononuclear cell proliferation and
      cytokine production.
AB  - BACKGROUND: Season of birth has been associated with the development of atopy and
      asthma. Relationships among a particular birth season, maternal allergen exposure
      during the birth season, and childhood development of allergies to allergens in
      higher concentration during the birth season may be important. OBJECTIVE: To
      investigate the effects of winter birth (January 1 to March 31) and prenatal
      cockroach and mouse allergens in settled dust on indoor allergen-specific cord
      blood mononuclear cell (CBMC) proliferation, TH2 production, and cord blood IgE
      concentration. METHODS: As part of an ongoing prospective study, 350 cord blood
      samples were collected. The CBMCs were cultured with cockroach, dust mite, and
      mouse protein extracts, and proliferation was measured. Interleukin 5, interferon
      delta, and total IgE levels were measured. Home dust samples were analyzed for
      cockroach and mouse allergens. RESULTS: An isolated association was observed
      between winter birth and a greater mean (SD) cockroach interleukin 5 ratio
      (winter vs nonwinter birth: 26,043 [11,403] vs 11,344 [3,701]; P = .02). Other
      associations between winter birth and increased CBMC proliferation, T-helper
      cytokines, or cord blood IgE levels were not detected. Higher mouse allergen
      levels were associated with decreased mouse-induced proliferation (winter vs
      nonwinter birth: mean [SD] stimulation index, 1.72 [0.12] vs 2.02 [0.11]; P =
      .04). CONCLUSIONS: Winter birth and increased cockroach or mouse allergen levels
      during pregnancy were not consistently associated with greater CBMC
      proliferation, T-helper cytokine production, or cord blood IgE levels. Greater
      indoor allergen exposure during pregnancy does not seem to affect the development
      of cockroach or mouse immune responses in utero.

PMID- 18727477
TI  - Allergy to kiwi in patients with baker's asthma: identification of potential
      cross-reactive allergens.
AB  - BACKGROUND: Baker's asthma is a frequent IgE-mediated occupational disorder
      mainly provoked by inhalation of cereal flour. Allergy to kiwifruit has being
      increasingly reported in the past few years. No association between both allergic
      disorders has been described so far. METHODS: Twenty patients with occupational
      asthma caused by wheat flour inhalation were studied. Kiwi allergens Act d 1 and
      Act d 2 were purified by cation-exchange chromatography. Wheat, rye, and kiwi
      extracts, purified kiwi allergens, and model plant glycoproteins were analyzed by
      IgE immunodetection, enzyme-linked immunosorbent assay (ELISA), and inhibition
      ELISAs. RESULTS: Kiwifruit ingestion elicited oral allergy syndrome in 7 of the
      20 patients (35%) with baker's asthma. Positive specific IgE and skin prick test
      responses to this fruit were found in all these kiwi allergic patients, and IgE
      to Act d 1 and Act d 2 was detected in 57% and 43%, respectively, of the
      corresponding sera. Actinidin Act d 1 and bromelain (harboring cross-reactive
      carbohydrate determinants) reached above 50% inhibition of the IgE binding to
      wheat and/or kiwi extracts. CONCLUSIONS: A potential association between
      respiratory allergy to cereal flour and allergy to kiwifruit has been disclosed.
      Cross-reactive carbohydrate determinants and thiol-proteaseshomologous to Act d 1
      are responsible for wheat-kiwi crossreactivity in some patients.

PMID- 18727478
TI  - Preventive effects of sublingual immunotherapy in childhood: an open randomized
      controlled study.
AB  - BACKGROUND: Sublingual immunotherapy (SLIT) has been proved to be effective in
      allergic rhinitis and asthma, but there are few data on its preventive effects,
      especially in children. OBJECTIVE: To evaluate the clinical and preventive
      effects of SLIT in children by assessing onset of persistent asthma and new
      sensitizations, clinical symptoms, and bronchial hyperreactivity. METHODS: A
      total of 216 children with allergic rhinitis, with or without intermittent
      asthma, were evaluated and then randomized to receive drugs alone or drugs plus
      SLIT openly for 3 years. The clinical score was assessed yearly during allergen
      exposure. Pulmonary function testing, methacholine challenge, and skin prick
      testing were performed at the beginning and end of the study. RESULTS: One
      hundred forty-four children received SLIT and 72 received drugs only. Dropouts
      were 9.7% in the SLIT group and 8.3% in the controls. New sensitizations appeared
      in 34.8% of controls and in 3.1% of SLIT patients (odds ratio, 16.85; 95%
      confidence interval, 5.73-49.13). Mild persistent asthma was less frequent in
      SLIT patients (odds ratio, 0.04; 95% confidence interval, 0.01-0.17). There was a
      significant decrease in clinical scores in the SLIT group vs the control group
      since the first year. The number of children with a positive methacholine
      challenge result decreased significantly after 3 years only in the SLIT group.
      Adherence was 80% or higher in 73.8% of patients. Only 1 patient reported
      systemic itching. CONCLUSIONS: In everyday clinical practice, SLIT reduced the
      onset of new sensitizations and mild persistent asthma and decreased bronchial
      hyperreactivity in children with respiratory allergy.

PMID- 18727479
TI  - The use of commercially available genetic tests in immunodeficiency disorders.

PMID- 18727480
TI  - Schnitzler syndrome successfully treated with methotrexate.

PMID- 18727481
TI  - Successful use of C1 inhibitor during mitral valve replacement surgery with
      cardiopulmonary bypass.

PMID- 18727482
TI  - Additional information on the pancake syndrome.

PMID- 18727484
TI  - Immunology, phenotype first. Preface.

PMID- 18727483
TI  - The subthalamic nucleus. Part I: development, cytology, topography and
      connections.
AB  - This monograph (Part I of two volumes) on the subthalamic nucleus (STN)
      accentuates the gap between experimental animal and human information concerning
      subthalamic development, cytology, topography and connections. The light and
      electron microscopical cytology focuses on the open nucleus concept and the
      neuronal types present in the STN. The cytochemistry encompasses enzymes, NO,
      glial fibrillary acidic protein (GFAP), calcium binding proteins, and receptors
      (dopamine, cannabinoid, opioid, glutamate, gamma-aminobutyric acid (GABA),
      serotonin, cholinergic, and calcium channels). The ontogeny of the subthalamic
      cell cord is also reviewed. The topography concerns the rat, cat, baboon and
      human STN. The descriptions of the connections are also given from a historical
      point of view. Recent tracer studies on the rat nigro-subthalamic connection
      revealed contralateral projections. Part II of the two volumes (volume 199) on
      the subthalamic nucleus (STN) starts with a systemic model of the basal ganglia
      to evaluate the position of the STN in the direct, indirect and hyperdirect
      pathways. A summary of in vitro studies is given, describing STN spontaneous
      activity as well as responses to depolarizing and hyperpolarizing inputs and high
      frequency stimulation. STN bursting activity and the underlying ionic mechanisms
      are investigated. Deep brain stimulation used for symptomatic treatment of
      Parkinson's disease is discussed in terms of the elements that are influenced and
      its hypothesized mechanisms. This part of the monograph explores the
      pedunculopontine-subthalamic connections and summarizes attempts to mimic
      neurotransmitter actions of the pedunculopontine nucleus in cell cultures and
      high-frequency stimulation on cultured dissociated rat subthalamic neurons. STN
      cell models--single- and multi-compartment models and system-level models are
      discussed in relation to subthalamic function and dysfunction. Parts I and II are
      compared.

PMID- 18727485
TI  - The forward genetic dissection of afferent innate immunity.
AB  - Recognition of the microbial world is mediated chiefly by a small group of immune
      receptors that activate a characteristic host inflammatory response, the innate
      immune response. Known as the Toll-like receptors (TLRs), these molecules are
      represented among most metazoans. In mammals, forward genetic analysis of the
      lipopolysaccharide (LPS) response led to the identification of TLR4 as the LPS
      receptor. Through a combination of forward and reverse genetic studies, a
      relatively detailed understanding of the functions of mammalian TLRs has now been
      achieved. As discussed here, mutagenesis has revealed proteins that participate
      in TLR signaling pathways, and informed our understanding of the subtleties of
      these molecules' structure and function.

PMID- 18727486
TI  - Genetic analysis of resistance to infections in mice: A/J meets C57BL/6J.
AB  - Susceptibility to infectious diseases has long been known to have a genetic
      component in human populations. This genetic effect is often complex and
      difficult to study as it is further modified by environmental factors including
      the disease-causing pathogen itself. The laboratory mouse has proved a useful
      alternative to implement a genetic approach to study host defenses against
      infections. Our laboratory has used genetic analysis and positional cloning to
      characterize single and multi-gene effects regulating inter-strain differences in
      the susceptibility of A/J and C57BL/6J mice to infection with several bacterial
      and parasitic pathogens. This has led to the identification of several proteins
      including Nrampl (Slc11a1), Birc1e, Icsbp, C5a, and others that play critical
      roles in the antimicrobial defenses of macrophages against intracellular
      pathogens. The use of AcB/BcA recombinant congenic strains has further
      facilitated the characterization of single gene effects in complex traits such as
      susceptibility to malaria. The genetic identification of erythrocyte pyruvate
      kinase (Pklr) and myeloid pantetheinase enzymes (Vnn1/3) as key regulators of
      blood-stage parasitemia has suggested that cellular redox potential may be a key
      biochemical determinant of Plasmodium parasite replication. Expanding these types
      of studies to additional inbred strains and to emerging stocks of mutagenized
      mice will undoubtedly continue to unravel the molecular basis of host defense
      against infections.

PMID- 18727487
TI  - Host defenses against human papillomaviruses: lessons from epidermodysplasia
      verruciformis.
AB  - Epidermodysplasia verruciformis (EV) is a rare, autosomal recessive
      genodermatosis associated with a high risk of skin carcinoma (MIM 226400). EV is
      characterized by the abnormal susceptibility of otherwise healthy patients to
      infection by specific, weakly virulent human papillomaviruses (HPVs), including
      the potentially oncogenic HPV-5. Inactivating mutations in either of the related
      EVER1/TMC6 and EVER2/TMC8 genes cause most EV cases. New insights in EV
      pathogenesis have been gained from the following recent observations: (1) EV
      specific HPVs (betapapillomaviruses) are defective for an important growth
      promoting function encoded by an E5/E8 gene present in other HPVs, and
      inactivation of EVER proteins may compensate for the missing viral function; (2)
      the transmembrane viral E5/E8 and cellular EVER proteins interact both with the
      zinc transporter ZnT1, and are likely to modulate zinc homeostasis. EV may thus
      represent a primary deficiency in intrinsic, constitutive immunity to
      betapapillomaviruses, or constitute a primary deficiency in innate immunity (or
      both). Keratinocytes, the home cells of HPVs, are likely to play a central role
      in both cases. An important issue is to establish which cellular genes involved
      in intrinsic and innate antiviral responses play a part in the outcome of
      infections with other HPV types, such as genital oncogenic HPVs.

PMID- 18727488
TI  - Innate resistance to flavivirus infections and the functions of 2'-5'
      oligoadenylate synthetases.
AB  - Mouse susceptibility to experimental infections with flaviviruses is
      significantly influenced by a cluster of genes on chromosome 5 encoding a family
      of proteins with enzymatic properties, the 2'-5' oligoadenylate synthetases
      (OAS). Positional cloning of the locus in question has revealed that
      susceptibility of laboratory inbred strains to this class of virus is associated
      with a nonsense mutation in the gene encoding the OAS1B isoform. Analysis of the
      molecular structure of the cluster in different mammalian species including human
      indicates that the cluster is extremely polymorphic with a highly variable number
      of genes and pseudogenes whose functions are not yet completely established.
      Although still preliminary, a few recent observations also substantiate a
      possible role for OAS1 in human susceptibility to viral infections (West Nile
      virus, SARS, etc.) and its possible involvement in some other diseases such as
      type 1 diabetes and multiple sclerosis. Finally, convergent observations indicate
      that the molecules encoded by the 2 '-5' OAS cluster might be involved in other
      fundamental cellular functions such as cell growth and differentiation, gene
      regulation, and apoptosis.

PMID- 18727489
TI  - Cmv1 and natural killer cell responses to murine cytomegalovirus infection.
AB  - The dissection of genetic resistance to murine cytomegalovirus infection in
      inbred laboratory mouse strains led to the identification of a natural killer
      cell activation receptor that recognizes a virus-encoded protein. Herein, we
      summarize the genetic approach and findings that have provided novel insights
      into innate immune control of virus infections.

PMID- 18727490
TI  - Genetic dissection of host resistance to Mycobacterium tuberculosis: the sst1
      locus and the Ipr1 gene.
AB  - Genetic variation of the host significantly contributes to dramatic differences
      in the outcomes of natural infection with virulent Mycobacterium tuberculosis
      (MTB) in humans, as well as in experimental animal models. Host resistance to
      tuberculosis is a complex multifactorial genetic trait in which many genetic
      polymorphisms contribute to the phenotype, while their individual contributions
      are influenced by gene-gene and gene-environment interactions. The most
      epidemiologically significant form of tuberculosis infection in humans is
      pulmonary tuberculosis. Factors that predispose immunocompetent individuals to
      this outcome, however, are largely unknown. Using an experimental mouse model of
      infection with virulent MTB for the genetic analysis of host resistance to this
      pathogen, we have identified several tuberculosis susceptibility loci in
      otherwise immunocompetent mice. The sst1 locus has been mapped to mouse
      chromosome 1 and shown to be especially important for control of pulmonary
      tuberculosis. Rampant progression of tuberculosis infection in the lungs of the
      sst1-susceptible mouse was associated with the development of necrotic lung
      lesions, which was prevented by the sst1-resistant allele. Using a positional
      cloning approach, we have identified a novel host resistance gene, Ipr1, which is
      encoded within the sst1 locus and mediates innate immunity to the intracellular
      bacterial pathogens MTB and Listeria monocytogenes. The sst1 locus and the Ipr1
      gene participate in control of intracellular multiplication of virulent MTB and
      have an effect on the infected macrophages' mechanism of cell death. The Ipr1 is
      an interferon-inducible nuclear protein that dynamically associates with other
      nuclear proteins in macrophages primed with interferons or infected with MTB.
      Several of the Ipr1-interacting proteins are known to participate in regulation
      of transcription, RNA processing, and apoptosis. Further biochemical analysis of
      the Ipr1-mediated pathway will help delineate a mechanism of innate immunity that
      is especially important for control of tuberculosis progression in the lungs.

PMID- 18727491
TI  - Scurfy, the Foxp3 locus, and the molecular basis of peripheral tolerance.
AB  - The ability to rapidly and efficiently recognize and eliminate pathogens while
      sparing normal self tissue is a hallmark of the mammalian immune system. When it
      fails, however, autoimmune disease results. The genetic and environmental factors
      that control the process of making such distinctions, not to mention the specific
      targeted tissues, are extraordinarily complex in the human population; only now
      are we characterizing the candidate genes responsible for these responses to
      pathogens. The examination of specific traits in murine models of disease has led
      to the identification of many of the candidate genes for human disease. The study
      of mouse mutations (both induced and spontaneous) has also greatly advanced our
      understanding of the immune responses and autoimmune disease. Here, we describe
      the use of classical mouse genetics to identify one gene centrally involved in
      the control of immune responses. Furthermore, although mutations in the
      orthologous human gene result in a virtually identical phenotype to that seen in
      the mouse, it is unlikely that studying the human disease populations alone would
      have successfully identified this gene. Thus, despite the complete sequencing of
      the human and mouse genomes, the examination of murine mutations remains a
      powerful and unbiased tool to connect genotype and phenotype.

PMID- 18727492
TI  - Fevers, genes, and innate immunity.
AB  - The characterization of patients with recurrent inflammatory syndromes into
      distinct clinical phenotypes provided early clues to the mode of inheritance of
      these conditions and facilitated the subsequent identification of causative gene
      mutations. The prototype autoinflammatory syndrome, familial Mediterranean fever,
      is characterized by self-limiting episodes of localized inflammation. Hallmarks
      of the classical autoimmune response are largely absent. The use of positional
      cloning techniques led to the identification of the causative gene, MEFV, and its
      product pyrin. This previously unrecognized protein plays an important role in
      modulating the innate immune response. Cryopyrin, the protein encoded by CIAS1,
      is mutated in a spectrum of autoinflammatory conditions, the cryopyrinopathies.
      In response to a wide range of potential pathogens, it forms a macromolecular
      complex termed the "inflammasome," resulting in caspase-1 activation and
      subsequent release of the active proinflammatory cytokine interleukin-1beta (IL
      1beta). The role of an established biochemical pathway in regulating inflammation
      was uncovered by the discovery that the hyperimmunoglobulin D with periodic fever
      syndrome (HIDS) results from mutations in MVK, which encodes an enzyme in the
      isoprenoid pathway. The discovery that mutations in the gene encoding tumor
      necrosis factor (TNF) receptor 1 (TNFR1) cause a proinflammatory phenotype was
      unanticipated, as it seemed more likely that such mutations would instead have
      resulted in an immunodeficiency pattern. This review describes the clinical
      phenotypes of autoinflammatory syndromes, the underlying gene mutations, and
      current concepts regarding their pathophysiology.

PMID- 18727493
TI  - Itchy mice: the identification of a new pathway for the development of
      autoimmunity.
AB  - Itchy mice possess a loss-of-function mutation in a HECT-domain-containing
      ubiquitin ligase (E3), Itch. Homozygous itchy mice develop a systemic and
      progressive autoimmune disease that proves lethal beginning at 6 months of age.
      Numerous targets of Itch-mediated ubiquitination have been identified, and some
      of these have defined physiological roles for Itch signaling in Tcell anergy and
      T cell differentiation. Studies of itchy mice have also allowed for the
      identification of a novel pathway involved in autoimmunity: noncanonical Notch
      signaling. In itchy mice carrying an activated Notch1 transgene, there are
      increased amounts of full-length Notch1, which can complex with p56(lck) and PI3K
      to activate a cell survival signal that is mediated by phospho-AKT. This, in
      turn, leads to a reduction in apoptosis in the thymus and may have consequences
      in T cell tolerance. A role for noncanonical Notch signaling in autoimmune
      disease is also supported by numerous mouse knockout studies, and suggests
      possible new therapeutic approaches for the treatment of autoimmune disease.

PMID- 18727494
TI  - TIM gene family and their role in atopic diseases.
AB  - The TIM gene family was discovered seven years ago by positional cloning in a
      mouse model of asthma and allergy. Three of the family members (TIM-1, TIM-3, and
      TIM-4) are conserved between mouse and man, and have been shown to critically
      regulate adaptive immunity. In addition, TIM-1 has been shown to play a major
      role as a human susceptibility gene for asthma, allergy and autoimmunity.
      Recently, TIM-4 has been identified as a ligand of phosphatidylserine and to
      control the uptake of apoptotic cells. These studies together suggest that the
      TIM gene family evolved to regulate immune responses by managing survival and
      cell death of hematopoetic cells.

PMID- 18727495
TI  - The subthalamic nucleus part II: modelling and simulation of activity.
AB  - Part I of The Subthalamic Nucleus (volume 198) (STN) accentuates the gap between
      experimental animal and human information concerning subthalamic development,
      cytology, topography and connections.The light and electron microscopical
      cytology focuses on the open nucleus concept and the neuronal types present in
      the STN. The cytochemistry encompasses enzymes, NO, glial fibrillary acidic
      protein (GFAP), calcium binding proteins, and receptors (dopamine, cannabinoid,
      opioid, glutamate, gamma-aminobutyric acid (GABA), serotonin, cholinergic, and
      calcium channels). The ontogeny of the subthalamic cell cord is also reviewed.
      The topography concerns the rat, cat, baboon and human STN. The descriptions of
      the connections are also given from a historical point of view. Recent tracer
      studies on the rat nigro-subthalamic connection revealed contralateral
      projections. This monograph (Part II of the two volumes) on the subthalamic
      nucleus (STN) starts with a systemic model of the basal ganglia to evaluate the
      position of the STN in the direct, indirect and hyperdirect pathways. A summary
      of in vitro studies is given, describing STN spontaneous activity as well as
      responses to depolarizing and hyperpolarizing inputs and high-frequency
      stimulation. STN bursting activity and the underlying ionic mechanisms are
      investigated. Deep brain stimulation used for symptomatic treatment of
      Parkinson's disease is discussed in terms of the elements that are influenced and
      its hypothesized mechanisms. This part of the monograph explores the
      pedunculopontine-subthalamic connections and summarizes attempts to mimic
      neurotransmitter actions of the pedunculopontine nucleus in cell cultures and
      high-frequency stimulation on cultured dissociated rat subthalamic neurons. STN
      cell models - single- and multi-compartment models and system-level models are
      discussed in relation to subthalamic function and dysfunction. Parts I and II are
      compared.

PMID- 18727496
TI  - The multiplicity of mutations in human cancers.

PMID- 18727497
TI  - Monitoring chromosome rearrangements.

PMID- 18727498
TI  - Nucleotide excision repair and its connection with cancer and ageing.

PMID- 18727499
TI  - DNA mismatch repair and colon cancer.

PMID- 18727500
TI  - Base excision repair.

PMID- 18727501
TI  - Genomic instability in cancer development.

PMID- 18727502
TI  - Translesion synthesis and error-prone polymerases.

PMID- 18727503
TI  - The Ink4a/Arf network--cell cycle checkpoint or emergency brake?

PMID- 18727504
TI  - DNA replication and genomic instability.

PMID- 18727505
TI  - The dream of every chromosome: equal segregation for a healthy life of the host.

PMID- 18727506
TI  - Telomere structural dynamics in genome integrity control and carcinogenesis.

PMID- 18727507
TI  - Gene amplification mechanisms.

PMID- 18727508
TI  - DNA methylation and cancer-associated genetic instability.

PMID- 18727509
TI  - Deregulation of the centrosome cycle and the origin of chromosomal instability in
      cancer.
AB  - Although we have begun to tap into the mechanisms behind Boveri's initial
      observation that supernumerary centrosomes cause chromosome missegregation in sea
      urchin eggs, there is still much left to discover with regard to chromosomal
      instability in cancer. Many of the molecular players involved in regulation of
      the centrosome and cell cycles, and the coupling of the two cycles to produce a
      bipolar mitotic spindle have been identified. One theme that has become apparent
      is that cross talk and interrelatedness of the pathways serve to provide
      redundant mechanisms to maintain genomic integrity. In spite of this, cells
      occasionally fall prey to insults that initiate and maintain the chromosomal
      instability that results in viable malignant tumours. Deregulation of centrosome
      structure is an integral aspect of the origin of chromosomal instability in many
      cancers. There are numerous routes to centrosome amplification including:
      environmental insults such as ionising radiation and exposure to estrogen (Li et
      al., 2005); failure of cytokinesis; and activating mutations in key regulators of
      centrosome structure and function. There are two models for initiation of
      centrosome amplification (Figure 2). In the first, centrosome duplication and
      chromosome replication remain coupled and cells enter G2 with 4N chromosomes and
      duplicated centrosomes. However, these cells may fail to complete mitosis, and
      thus reenter G1 as tetraploid cells with amplified centrosomes. In the second,
      the centrosome cycle is uncoupled from chromosome replication and cells go
      through one or more rounds of centriole/centrosome duplication in the absence of
      chromosome replication. If these cells then go through chromosome replication
      accompanied by another round of centrosome duplication, cells complete G2 with 4N
      chromosomes and more than 2 centrosomes, and therefore are predisposed to
      generate multipolar mitotic spindles. Fragmentation of centrosomes due to
      ionising radiation is a variation of the second model. Once centrosome
      amplification is present, even in a diploid cell, that cell has the potential to
      yield viable aneuploid progeny. The telophase cell in Figure 3C illustrates this
      scenario. In a normal telophase configuration, the total number of chromosomes is
      92 (resulting from the segregation of 46 pairs of chromatids), with each daughter
      nucleus containing 46 individual chromosomes. Based on the number of kinetochore
      signals present, the lower nucleus in Figure 3C has approximately 28 chromosomes,
      and the elongate upper nucleus has approximately 60, for a total of 88. Due to
      superimposition of kinetochores in this maximum projection image, 88 is an
      underestimate of the actual number of kinetochores and is not significantly
      different from the expected total of 92. A cell resulting from the lower nucleus
      with only around 28 chromosomes would probably not be viable, much as Boveri's
      experiments indicated. However, the upper nucleus with at least 60 chromosomes
      could be viable. This cell would enter G1 as hypotriploid (69 chromosomes =
      triploid) with 2 centrosomes. During S and G2, the centrosomes and chromosomes
      would double, and the following mitosis could be tetrapolar with a 6N chromosome
      content. When centrosome amplification is accompanied by permissive lapses in
      cell cycle checkpoints, the potential for malignant growth is present. These
      lapses could result from specific genetic mutations and amplifications,
      epigenetic gene silencing, or from massive chromosomal instability caused by the
      centrosome amplification. Centrosome amplification, therefore, can serve to
      exacerbate and/or generate genetic instabilities associated with cancers.

PMID- 18727510
TI  - Mammalian DNA damage response pathway.

PMID- 18727511
TI  - Atm and cellular response to DNA damage.

PMID- 18727512
TI  - Mitotic checkpoint, aneuploidy and cancer.

PMID- 18727513
TI  - [Effect of lipopolysaccharide on cyclooxygenase-2 expression and prostaglandin E2
      release in human nasal epithelia].
AB  - OBJECTIVE: To detect cyclooxygenase-2 (COX-2) expression and prostaglandin E2
      (PGE2) release in human nasal epithelia (HNE) induced by lipopolysaccharide (LPS)
      in different concentration gradient and time gradient, and to investigate their
      roles in nasal inflammatory pathogenesis. METHOD: Western Blot and fluorescent
      real time quantitative PCR were performed to detect the expression of COX-2 in
      HNE induced by LPS and blocked by selective inhibitor of COX-2. The
      concentrations of PGE2 were determined by enzyme immunoassay. RESULT: Low
      expressions of COX-2 and PGE2 were detected in normal HNE. COX-2 expression and
      PGE2 release increased in HNE induced by LPS in time-dependent or dose-dependent
      manner. The increased release of PGE2 was later than that of COX-2 expression.
      COX-2 expression and PGE2 release were dose-dependently attenuated by selective
      inhibitor of COX-2. CONCLUSION: LPS effectively induces COX-2 expression and PGE2
      release in HNE. And COX-2 is responsible for the synthesis of PGE2. These results
      indicate that the increased expression of COX-2 and PGE2 is involved in the
      inflammation of HNE induced by LPS in vitro.

PMID- 18727514
TI  - [Comparative study of front-ethmoid-orbital mass resection via trans scalp
      coronary incision and functional endoscopic sinus surgery].
AB  - OBJECTIVE: To investigate the advantages and disadvantages between two surgical
      approaches of trans scalp coronary incision (TCI) and functional endoscopic sinus
      surgery (FESS) by which front-ethmoid-orbital masses being resected. METHOD:
      Thirty-four cases of front-ethmoid-orbital mass from 1995-2006 were
      retrospectively studied, among which lesions of 18 cases resected by FESS,
      lesions of 16 cases via TCI. The follow-up time varied from 2 to 4 years. RESULT:
      Five of 18 cases by FESS had residual dizziness or nasal pain, one case recurred
      2 years after the operation. None of TCI cases experienced recurrence, whereas
      dizziness presented in 3 cases, regional dull sensation of the operative scalp in
      12 cases. CONCLUSION: FESS and TCI approach has its own benefits and shortcomings
      thus has its indications respectively.

PMID- 18727515
TI  - [Expression and clinical significance of hypoxia-inducible factor-1alpha and
      angiopoietin-2 in laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the expressions and clinical significance of Hypoxia
      Inducible Factor-1alpha (HIF-1alpha) and angiopoietin-2 (Ang-2) proteins in
      laryngeal squamous cell carcinoma. METHOD: Immunohistochemical technique was used
      to detect the expressions of HIF-1alpha and Ang-2 protein in 52 laryngeal
      squamous cell carcinoma and 10 normal tissues. RESULT: The positive rates of HIF
      1alpha and Ang-2 proteins were significantly higher in laryngeal squamous cell
      carcinoma than those in normal tissues (P < 0.05). The expressions of HIF-1alpha
      protein was related with TNM stage and lymph node metastasis (P < 0.05), but had
      no marked correlations with the sex, age and histological differentiation (P >
      0.05). The level of Ang-2 expression was also correlated with TNM stage, lymph
      node metastasis and histological differentiation of laryngeal squamous cell
      carcinoma. But not related to the age and sex. There was positive correlations
      between both expressions of HIF-1alpha and Ang-2 proteins (r = 0. 333, P < 0.01).
      CONCLUSION: High expressions of HIF-1alpha and Ang-2 proteins in laryngeal
      squamous cell carcinoma may play an important role in tumor growth, invasion and
      metastasis.

PMID- 18727516
TI  - [Effect of adenoidectomy on pediatric chronic rhinosinusitis].
AB  - OBJECTIVE: To explore the effect of adenoidectomy on pediatric chronic
      rhinosinusitis. METHOD: A total of 51 pediatric patients with chronic
      rhinosinusitis were included in this study. There were 17 cases underwent
      adenoidectomy, 12 cases underwent endoscopic sinus surgery,and 22 cases underwent
      both adenoidectomy and endoscopic sinus surgery. RESULT: There was significant
      differences in the efficiencies between endoscopic sinus surgery group and both
      adenoidectomy and endoscopic sinus surgery group. CONCLUSION: Adenoidectomy is
      effective treatment for sinusitis in children.

PMID- 18727517
TI  - [Gene expression profiles in human nasal polyps studied by DNA microarray].
AB  - OBJECTIVE: To explore the changes in gene expressions in the human nasal polyp.
      METHOD: A 14500 gerie DNA microarray (Affymetrix) was used to examine gene
      expressions in 6 NP samples, 6 normal mucosal samples. The differentially
      expressed genes were identified and subjected to realtime PCR analysis. RESULTS:
      The differentially expressed genes mostly involved in cytokines, adhesion genes
      about complements and their receptors, immune transcription regulatory molecules,
      signal transduction, differentially expressed genes including IL-8, RGS1, GRK4,
      CCL20, uteroglobin. The results of IL-8, RGS1 Real-time PCR of were consistent
      with that of gene chip analysis. CONCLUSION: Microarray expression profile of NP
      samples is differential. RGS1 may play an important role in cell signal
      transduction, IL-8 may involve in occurrence of nasal polyps by inducing cells
      releasing inflammatory factors.

PMID- 18727518
TI  - [Clinical analysis of 19 cases of esthesioneuroblastoma under classic surgical
      approaches and surgical approaches with the assistant of nose endoscope].
AB  - OBJECTIVE: To summarize the curative effect and esthesioneuroblastoma (ENB) by
      classic surgical approaches and surgical approaches with the assistant of nose
      endoscope. METHOD: A retrospective review was conducted in 19 cases treated from
      1980 to 2000. Ten cases were treated by classical surgical approaches. Tumors in
      4 patients (According to the Kadish system, stage A, 3 cases; stage B, 1 case)
      were removed via a transnasal approach, 6 patients (stage B, 5 cases; stage C, 1
      case) were performed by lateral rhinotomy. After 1995, 9 cases (stageA, 2 case;
      stageB, 5 cases; stageC, 2 cases) received surgical resection with nasale
      endoscope. All of the patients were conducted radiation after operation. RESULT:
      The 5-year survival rate for the classic procedure and the surgical procedure
      with the assistant of endoscope were 50.0%, 88.9%, respectively. And the local
      recurrence rates were 50.0%, 33.3%, respectively (had no statistical
      significance). And the mean recurrent time were 5.2 months, 16 months,
      respectively. With the assistant of endoscope, the recurrent time was significant
      retarded. CONCLUSION: There are better illumination and better operation field
      during the surgical operation with the assistant of endoscope. And the tumors are
      more likely resected entirely and the tumor recurrent time could be deferred.

PMID- 18727519
TI  - [Expression and significance of integrin beta1 and integrin-linked kinase in
      laryngeal carcinoma].
AB  - OBJECTIVE: To study the expressions and clinical significance of integrin beta1
      and integrin-linked kinase(ILK) in laryngeal carcinoma (LSCC). METHOD: The mRNA
      and protein levels of integrinbeta1 and integrin-linked kinase in 43 specimens of
      laryngeal carcinoma, its surrounding tissue and 18 specimens of vocal cord polyp
      were detected by reverse transcription-polymerase chain reaction (RT-PCR) and
      immunohistochemistry SABC method. RESULT: The mRNA levels of integrin beta1 and
      ILK protein were significantly higher in laryngeal carcinoma than that in its
      surrounding tissue and vocal cord polyp (P < 0.05). There was significant
      correlation between the levels of integrin beta1 expression and the status of
      cervical lymph node, either between the level of ILK expression and cervical
      lymph node status (P < 0.05). There was significant correlation between the
      levels of integrin beta1 expression and T-category, either between the level of
      ILK expression and T-category (P < 0.05). But pathological grades was not
      significantly related with the level of integrin beta1 or ILK expression (P >
      0.05). CONCLUSION: The expressions of integrin beta1 and ILK are increased in
      LSCC. Integrin beta1 and ILK may contribute significantly to invasion and
      metastasis of LSCC.

PMID- 18727520
TI  - [Study on the surgery treatments in patients with maxillary osteofibrous
      hyperplasia of bone].
AB  - OBJECTIVE: To explore the clinical features, diagnosis and the surgery therapy of
      maxillary fibrous hyperplasia of bone. METHOD: The clinical data of 37 cases with
      maxillary fibrous hyperplasia of bone from 1987-2006 years were retrospectively
      analyzed. 19 cases of male and 18 cases of female, their average age is 22.5
      years (17-35 years). Twenty-one cases were operated by Caldwell-lud or lateral
      rhinotomy operation. After 1997, 16 cases were operated by Caldwell-lud operation
      with endoscopy so as to strip hyperplasia bone. RESULT: Thirty-six cases were
      cured within 2-4 years follow-up, 1 case was reoperated by Caldwell-lud operation
      with endoscopy after recurrence. The patients who received operation by Caldwell
      lud operation with endoscopy had less symptoms in the inflation deformity of
      maxillofacial region and dysfunction of neighbouring structures than those who
      received traditional operation. CONCLUSION: The diagnosis can be made by history,
      signs and radiography. Caldwell-lud operation with nasal endoscopy is more
      effective treatment, and advocated in clinical practice.

PMID- 18727521
TI  - [Endoscopic surgery in sinonasal inverted papillomas].
AB  - OBJECTIVE: To evaluate the effect and application value of endoscopic resection
      in sinonasal inverted papillomas. METHOD: In a retrospective study, clinical data
      of 40 patients underwent transnasal endoscopic approach in Chinese PLA General
      Hospital from July 1999 to April 2005 were analyzed. Tumor stage according to
      Krouse was T1: 4, T2: 23, T3: 12, T4: 1, respectively. RESULT: All lesions were
      removed completely and 5 patients received post-operative radiation therapy.
      There were no serious complications occurred. The follow-up period ranged from 24
      to 93 months (mean, 45.1 months). Recurrence rate was 15% (6/40) and the rate of
      malignant transformation and mortality were 7.5 % (3/40), respectively. Average
      time to recurrence was 37.3 months. CONCLUSION: Endoscopic surgery offers a safe
      and effective treatment for sinonasal inverted papillomas with a minimally
      invasion. Thorough removal of the tumor and regular follow-up are the key points
      for success.

PMID- 18727522
TI  - [Effect of the intense noise on hearing function and cochlea morphology in rat].
AB  - OBJECTIVE: To observe the changes of auditory electrophysiology and inner ear
      pathology in rat cochlea after the noise exposure, and to offer the experimental
      data for exploring the mechanism of noise-damaged cochlea. METHOD: The rats in
      the study group were exposed to a intense narrow band noise centered at 4 kHz at
      the leave of 120 dB (SPL) for 4 h. The exposed cochleae were collected at various
      intervals (1 or 21 days) after the noise exposure. Auditory function was
      monitored by measuring thresholds of auditory brain stem responses (ABR). The
      morphological changes in rat cochlear hair cell (HC) were examined by HC nuclei
      stained with Propidium iodide (PI), a fluorescent dye specifically labelling the
      nuclear DNA and scanning electron microscopy (SEM). The number of spiral ganglion
      cells was calculated using pathologic technique. RESULT: The thresholds of ABR in
      the study group were significantly greater than that in the normal control group
      (P < 0.01). Examined at 1 day after the noise exposure, normal, apoptosis,
      necrotic and missing out hair cell (OHC) could be distinguished with PI staining,
      whereas the apoptosis OHC were not found at 21 days. Significant OHC loss was
      found in as compared to the normal control group (P < 0.01). There was not
      significant difference in the calculation of spiral ganglion cells (P > 0.05).
      SEM revealed the injured stereocilia of OHC (disarrangement, collapse) and OHC
      loss in the study group, which was more severe in OHC3 than the other two rows of
      OHC. CONCLUSION: The intense noise used in our study could injure the rat cochlea
      and bring permanent threshold shift (PTS). Under this condition, the death modes
      of HC in the cochlea include apoptosis and necrosis in the fore part, whereas
      necrotic is the major mode in the evening of exposure. The injured stereocilia of
      OHC and OHC loss could remain the most consistent correlate of PTS.

PMID- 18727524
TI  - Principles of gel permeation chromatography.

PMID- 18727523
TI  - [Effect of jieminqufeng decoction on cyclic nucleotides from the rats of allergic
      rhinitis].
AB  - OBJECTIVE: To observe the curative effect of Jieminqufeng decoction to the rats
      of allergic rhinitis and study the mechanism by which it treats allergic
      rhinitis. METHOD: Forty wistar rats were divided into 4 groups at random. There
      are Jieminqufeng decoction group, cetirizine group, model control group and
      normal control group. The rats of allergic rhinitis were established with
      ovalbumin. We surveyed the behavioral changes of rats, searched eosinophilic
      granulocytes in the nasal secretion, detected the contents of cAMP and cGMP in
      the blood plasma and nasal mucosa. RESULT: The model control group had typical
      symptoms of allergic rhinitis and the eosinophilic granulocytes could be found
      more frequently. The contents of cAMP and cAMP/cGMP rose in the blood plasma and
      nasal mucosa (P < 0.01). However, the changes of jieminqufeng decoction group
      were small. CONCLUSION: The jieminqufeng decoction is an effective drug to
      allergic rhinitis. Its possible mechanism is that it changes the contents of cAMP
      and cGMP, lessens inflammatory reaction and blocks up the allergy.

PMID- 18727525
TI  - Determination of decoquinate in animal feeds by liquid chromatography:
      collaborative study.
AB  - The performance characteristics of a liquid chromatographic (LC) method for the
      analysis of decoquinate (DEC) in supplements, premixes, and complete animal feeds
      at medicating and trace levels were collaboratively studied. DEC is extracted
      from ground feed samples with 1% calcium chloride-methanol solution using
      mechanical agitation for 90 min. After centrifugation for 5 min and dilution (if
      necessary), an aliquot of the extract is diluted with water. The diluted extracts
      are filtered and analyzed by reversed-phase LC with fluorescence detection.
      Suspect positive trace-level samples are confirmed by using an alternate
      excitation wavelength. Fourteen test samples of medicated feeds, supplement, and
      medicated premix, along with 8 test samples for trace-level analysis, were sent
      to 13 collaborators (one in Canada, 4 in Europe, and 8 in the United States).
      Test samples were analyzed as blind duplicates. Acceptable results were received
      from 12 laboratories for the medicated test samples and from 13 laboratories for
      the trace-level samples. Repeatability relative standard deviation estimates
      ranged from 1.3 to 5.6%. Reproducibility relative standard deviations estimates
      ranged from 2.8 to 6.1%, and HorRat values ranged from 0.22 to 0.74.

PMID- 18727526
TI  - Determination of hydrastine and berberine in goldenseal raw materials, extracts,
      and dietary supplements by high-performance liquid chromatography with UV:
      collaborative study.
AB  - A multilaboratory collaborative study was conducted on a high-performance liquid
      chromatographic (HPLC) method utilizing UV detection, previously validated using
      AOAC single-laboratory validation guidelines for determination of hydrastine and
      berberine in goldenseal (Hydrastis canadensis L.) raw materials, extracts, and
      dietary supplements at levels ranging from 0.4 to 6% (w/w). Nine collaborating
      laboratories determined the hydrastine and berberine content in 8 blind samples.
      Sample materials included powdered botanical raw materials, whole root material,
      and 4 finished product dietary supplements containing either goldenseal powdered
      root material or extract. The materials were extracted with an acidified water
      and acetonitrile solution. HPLC analyses of the extracts were performed on a C18
      column using UV detection at 230 nm. Results for powdered root material and
      capsule products ranged from about 0.2% (w/w) for each alkaloid to about 4% (w/w)
      for each alkaloid. Liquid tincture results were approximately 4000-5000 microg/mL
      for each alkaloid. Reproducibility relative standard deviations (RSDR) for
      hydrastine ranged from 2.68 to 6.65%, with HorRat values ranging from 0.77 to
      1.89. RSDR for berberine ranged from 5.66 to 7.68%, with HorRat values ranging
      from 1.32 to 2.12. All finished products containing goldenseal extract yielded
      HorRat values <2.0. Based on these results, the method is recommended for
      Official First Action for determination of hydrastine and berberine in goldenseal
      raw materials and dietary supplement finished products containing powdered
      goldenseal and goldenseal extract.

PMID- 18727527
TI  - Determination of coenzyme Q10 content in raw materials and dietary supplements by
      high-performance liquid chromatography-UV: collaborative study.
AB  - An international collaborative study was conducted of a high-performance liquid
      chromatographic (HPLC)-UV method for the determination of coenzyme Q10 (CoQ10,
      ubidecarenone) in raw materials and dietary supplements. Ten collaborating
      laboratories determined the total CoQ10 content in 8 blind duplicate samples.
      Sample materials included CoQ10 raw material and 4 finished product dietary
      supplements representing softgels, hardshell gelatin capsules, and chewable
      wafers. In addition, collaborating laboratories received a negative control and
      negative control spiked with CoQ10 at low and high levels to determine recovery.
      Materials were extracted with an acetonitrile-tetrahydrofuran-water mixture.
      Ferric chloride was added to the test solutions to ensure all CoQ10 was in the
      oxidized form. The HPLC analyses were performed on a C18 column using UV
      detection at 275 nm. Repeatability relative standard deviations (RSDr) ranged
      from 0.94 to 5.05%. Reproducibility relative standard deviations (RSDR) ranged
      from 3.08 to 17.1%, with HorRat values ranging from 1.26 to 5.17. Recoveries
      ranged from 74.0 to 115%. Based on these results, the method is recommended for
      Official First Action for determination of CoQ10 in raw materials and dietary
      supplement finished products containing CoQ10 at a concentration of >100 mg
      CoQ10/g test material.

PMID- 18727528
TI  - Ultraviolet-photodiode array and high-performance liquid chromatographic/mass
      spectrometric studies on forced degradation behavior of glibenclamide and
      development of a validated stability-indicating method.
AB  - A forced degradation study on glibenclamide was performed under conditions of
      hydrolysis, oxidation, dry heat, and photolysis and a high-performance column
      liquid chromatographic-ultraviolet (HPLC-UV) method was developed to study
      degradation behavior of the drug under the forced conditions. The degradation
      products formed under different forced conditions were characterized through
      isolation and subsequent infrared/nuclear magnetic resonance/mass spectral
      analyses, or through HPLC/mass spectrometric (HPLC/MS) studies. The drug degraded
      in 0.1 M HCI and water at 85 degrees C to a major degradation product, 5-chloro-2
      methoxy-N-2-(4-sulfamoylphenyl)ethyl]benzamide (III), and to a minor product, 1
      cyclohexyl-3-[[4-(2-aminoethyl)-phenyl]sulfonyl]urea (IV). Upon prolonged heating
      in the acid, the minor product IV disappeared, resulting in formation of 5-chloro
      2-methoxy-benzoic acid (II) and an unidentified product (I). Heating of the drug
      in 0.1 M NaOH at 85 degrees C yielded II and IV as the major products and I and
      III as the minor products. The drug and the degradation products formed under
      different conditions were optimally resolved on a C18 column using ammonium
      acetate buffer (0.025 M, pH 3.5)-acetonitrile (45 + 55) mobile phase at a flow
      rate of 0.6 mL/min, with detection at 230 nm. The method was validated for
      linearity, precision, accuracy, and specificity. Limit of detection (LOD) and
      limit of quantitation (LOQ) values were also determined. The method could be
      successfully applied for simultaneous quantification of glibenclamide and the
      major product, III. The response of the method was linear in a narrow [0.4-10
      micro/mL, correlation coefficient (r2) = 0.9982] and a wide (0.4-500 microg/mL,
      r2 = 0.9993) concentration range for glibenclamide, and in the concentration
      range of 0.025-50 microg/mL (r2 = 0.9998) for III. The method proved to be
      precise and accurate for both glibenclamide and III. It was specific for the drug
      and also selective for each degradation product, and LOQ values for the drug were
      0.1 and 0.4 microg/mL, whereas those for III were 0.010 and 0.025 microg/mL,
      respectively.

PMID- 18727529
TI  - Selective and stability-indicating methods for the simultaneous determination of
      mexiletine hydrochloride and/or its related substance: 2,6-dimethylphenol.
AB  - Four simple, rapid, sensitive, and selective analytical procedures were developed
      for determination of mexiletine hydrochloride (MX) and/or its related substance:
      2,6-dimethylphenol (DMP). The latter is a synthetic impurity for which a maximum
      pharmacopeial limit is defined. The first method depends on derivative-ratio
      spectrophotometry, for which the first-derivative signals of the ratio spectra at
      259 nm (Deltalambda = 3 nm) are selected for the determination of MX. The second
      method is based on the spectrofluorometric measurement of MX in alkaline solution
      in the presence of 15 mM sodium dodecyl sulfate micellar medium at 292 nm
      (lambdaEx 260 nm). The third method is based on liquid chromatographic (LC)
      separation of MX and DMP on an RP-C8 column with a mobile phase consisting of 50
      mM Na2HPO4-acetonitrile (60 + 40, adjusted to pH 2.4), and quantification of the
      analytes is achieved with UV detection at 212 nm based on peak area. The fourth
      method uses the coupling reaction of DMP with 2,6-dibromo-quinone-4-chlorimide
      (DBQC) in borate buffer to form an intensely colored product that was
      spectrophotometrically measured using first-derivative amplitudes at 670 nm
      (Deltalambda = 6 nm) for the determination of DMP. Different variables affecting
      each method were carefully investigated and optimized. The reliability and
      analytical performance of the proposed methods, including linearity, range,
      precision, accuracy, and detection and quantitation limits, were statistically
      validated. The first 3 methods were successfully applied for the stability
      indicating determination of MX in laboratory-prepared mixtures with DMP, as well
      as for the determination of MX in capsules. Also, the LC and the DBQC
      spectrophotometric methods permitted the selective determination of DMP in the
      presence of a large excess of the parent drug at or near the pharmacopeial limit
      (0.1-1%).

PMID- 18727530
TI  - Development and validation of a liquid chromatographic/tandem mass spectrometric
      method for determination of tetracycline in human plasma: application to
      bioequivalence study.
AB  - A fast, sensitive, and specific liquid chromatographic/tandem mass spectrometric
      method was developed and validated for determination of tetracycline in human
      plasma. Tetracycline and oxytetracycline [internal standard (IS)] were extracted
      from the plasma by protein precipitation. The mobile phase consisted of
      acetonitrile-formic acid 0.1% (48 + 52, v/v), run at a flow rate of 1 ml/min
      (split 1:5). Detection was performed by positive electrospray ionization in
      multiple reaction monitoring mode, monitoring the transitions 444.8 > 410.0 and
      461.0 > 426.0 for tetracycline and IS, respectively. The analysis was performed
      in 3.5 min and the method was linear in the plasma concentration range of 50-6000
      ng/mL. The mean extraction recoveries for tetracycline and IS from plasma were
      92.14 and 94.04%, respectively. Method validation investigated parameters such as
      the linearity, precision, accuracy, specificity, and stability, giving results
      within the acceptable range. The proposed method was successfully applied for
      determination of tetracycline in human plasma samples to support bioequivalence
      studies.

PMID- 18727531
TI  - Development of a new high-performance liquid chromatographic method for the
      determination of ceftazidime.
AB  - A rapid, accurate, and sensitive high-performance liquid chromatographic (HPLC)
      method was developed and validated for the determination of ceftazidime in
      pharmaceuticals. The method validation parameters yielded good results and
      included range, linearity, precision, accuracy, specificity, and recovery. The
      excipients in the commercial powder for injection did not interfere with the
      assay. Reversed-phase chromatography was used for the HPLC separation on a Waters
      C18 (WAT 054275; Milford, MA) column with methanol-water (70 + 30, v/v) as the
      mobile phase pumped isocratically at a flow rate of 1.0 mL/min. The effluent was
      monitored at 245 nm. The calibration graph for ceftazidime was linear from 50.0
      to 300.0 microg/mL. The values for interday and intraday precision (relative
      standard deviation) were <1%. The results obtained by the HPLC method were
      calculated statistically by analysis of variance. We concluded that the HPLC
      method is satisfactory for the determination of ceftazidime in the raw material
      and pharmaceuticals.

PMID- 18727532
TI  - Simultaneous determination of potassium clavulanate and cefixime in synthetic
      mixtures by high-performance liquid chromatography.
AB  - A simple, precise, and sensitive high-performance liquid chromatographic method
      was developed and validated for the simultaneous determination of potassium
      clavulanate and cefixime in synthetic mixture form. The analytes were separated
      on a C18 column by using 0.03 M disodium hydrogen phosphate buffer (pH 6.5)
      methanol (84 + 16, v/v) as the mobile phase with detection at 220 nm. The method
      exhibited high sensitivity and good linearity in the concentration ranges of 12.5
      62.5 and 20-100 microg/mL for potassium clavulanate and cefixime, respectively.
      The total run time for the 2 components was <8 min, and the average recovery was
      >101.5% with a relative standard deviation of <1.0%. The proposed method was
      validated according to guidelines of the International Conference on
      Harmonization by evaluation of linearity, recovery, selectivity, robustness,
      limits of detection and quantitation, and within- and between-day precision. The
      results obtained for the synthetic mixture show that the method is highly precise
      and accurate for the simultaneous determination of potassium clavulanate and
      cefixime.

PMID- 18727533
TI  - Simultaneous estimation of acetylsalicylic acid and clopidogrel bisulfate in pure
      powder and tablet formulations by high-performance column liquid chromatography
      and high-performance thin-layer chromatography.
AB  - This paper describes validated high-performance column liquid chromatographic
      (HPLC) and high-performance thin-layer chromatographic (HPTLC) methods for
      simultaneous estimation of acetylsalicylic acid (ASA) and clopidogrel bisulfate
      (CLP) in pure powder and formulations. The HPLC separation was achieved on a
      Nucleosil C8 column (150 mm length x 4.6 mm id, 5 microm particle size) using
      acetonitrile-phosphate buffer, pH 3.0 (55 + 45, v/v) mobile phase at a flow rate
      of 1.0 mL/min at ambient temperature. The HPTLC separation was achieved on an
      aluminum-backed layer of silica gel 60F254 using ethyl acetate-methanol-toluene
      glacial acetic acid (5.0 + 1.0 + 4.0 + 0.1, v/v/v/v) mobile phase. Quantitation
      was achieved with UV detection at 235 nm over the concentration range 4-24
      microg/mL for both drugs, with mean recoveries of 99.98 +/- 0.28 and 100.16 +/-
      0.66% for ASA and CLP, respectively, using the HPLC method. Quantitation was
      achieved with UV detection at 235 nm over the concentration range of 400-1400
      ng/spot for both drugs, with mean recoveries of 99.93 +/- 0.55 and 100.21 +/-
      0.83% for ASA and CLP, respectively, using the HPTLC method. These methods are
      simple, precise, and sensitive, and they are applicable for the simultaneous
      determination of ASA and CLP in pure powder and formulations.

PMID- 18727534
TI  - Development and validation of column high-performance liquid chromatographic and
      derivative spectrophotometric methods for determination of levofloxacin and
      ornidazole in combined dosage forms.
AB  - The manuscript describes validated reversed-phase column high-performance liquid
      chromatographic (RP-HPLC) and first-derivative UV spectrophotometric methods for
      the estimation of levofloxacin (LFX) and ornidazole (ORNI) in combined dosage
      forms. The RP-HPLC separation was achieved on a Phenomenex C18 column (250 mm x
      4.6 mm id, 5 microm) using KH2PO4 buffer (pH 6.8)-methanol-acetonitrile (70 + 15
      + 15, v/v/v) mobile phase at a flow rate of 1.5 mL/min and ambient temperature
      (25 +/- 2 degrees C). Quantification was achieved with photodiode array detection
      at 295 nm over the concentration range of 1-10 microg/mL for both LFX and ORNI,
      with mean recovery of 101.7 +/- 0.23 and 99.23 +/- 1.57%, respectively, by the RP
      HPLC method. The derivative spectrophotometric method was based on the
      determination of both the drugs at their respective zero crossing point (ZCP).
      The first-order derivative spectra were obtained at N = 1 (scaling factor),
      Deltalambda = 2.0 nm (wavelength interval), and the determinations were made at
      310 nm (ZCP of ORNI) for LFX and 295 nm (ZCP of LFX) for ORNI over the
      concentration range of 2-40 microg/mL for both LFX and ORNI. Mean recovery was
      99.46 +/- 0.96 and 100.9 +/- 0.72%, respectively, by the first-derivative UV
      spectrophotometric method. Standard and sample solutions were prepared with
      methanol as the solvent in both of the methods. These methods were found to be
      simple, accurate, precise, and sensitive and were applicable for the simultaneous
      determination of LFX and ORNI in combined dosage forms.

PMID- 18727535
TI  - Extraction of aflatoxins B1 and G1 from maize by using aqueous sodium dodecyl
      sulfate.
AB  - Aflatoxins are potent carcinogens produced by certain Aspergillus fungi. The
      aflatoxins were first discovered in the 1960s, and since then have been found to
      be distributed worldwide in a variety of commodities, foods, and feeds. Many of
      the early techniques for detecting aflatoxins involved extraction with
      halogenated solvents. With the increased availability and use of reversed-phase
      solid-phase extraction cartridges and the availability of immunoaffinity columns,
      aqueous mixtures of nonhalogenated solvents have been frequently used. To further
      reduce the need for solvents, we examined the effects of eliminating solvents
      during the extraction of maize, using aqueous mixtures of the detergent sodium
      dodecyl sulfate. After extraction and filtration, aflatoxins B1 (AFB1) and G1
      (AFG1) were isolated by using commercially available immunoaffinity columns. The
      isolated AFB1 and AFG1 were derivatized with trifluoroacetic acid before
      separation by liquid chromatography with fluorescence detection. In spiked maize,
      the limits of detection were 0.5 and 1 ng/g for AFB1 and AFG1, respectively.
      Recoveries of AFB1 from maize spiked at 1-20 ng/g averaged 87.5% (range, 76.3
      99.0%), with an average repeatability relative standard deviation (RSDr) of 4.0%.
      Recoveries of AFG1 from maize spiked at 2-20 ng/g averaged 80.4% (range, 70.3
      85.8%), with an average RSDr of 3.5%. This is the first reported demonstration of
      an effective solvent-free extraction of aflatoxins from maize at ambient
      pressure, and this extraction procedure may serve to help reduce solvent
      consumption during aflatoxin analysis.

PMID- 18727536
TI  - Effect of matrix on recovery of biogenic amines in fish.
AB  - Biogenic amines, such as putrescine, cadaverine, and histamine, in fish can be
      indicators of spoilage and/or safety. Methanol extraction used for AOAC Official
      Methods 996.07 and 977.13 has resulted in low amine recoveries in fish.
      Extraction methodology was evaluated to improve recovery from fish tissue.
      Samples were evaluated for recovery of known quantities of biogenic amines added
      to tissue prior to extraction. Addition of 25% 0.4 N HCI to the 75% methanol
      water extraction solvent (according to AOAC Official Methods 996.07 and 977.13)
      resulted in higher recoveries (P < 0.05) of the biogenic amines. Putrescine
      recovery increased from 44 +/- 2 to 100 +/- 14% in flounder and scup, and from 53
      +/- 21 to 119 +/- 27% in mackerel and butterfish; cadaverine recovery increased
      from 47 +/- 4 to 106 +/- 15% (flounder/scup) and 58 +/- 24 to 113 +/- 9%
      (mackerel/butterfish); histamine recovery increased from 54 +/- 13 to 89 +/- 28%
      (mackerel). MeOH extraction resulted in comparable recovery from canned tuna,
      indicating that protein denaturation from processing may eliminate possible
      matrix interference. Acidification of the solvent resulted in a more complete
      extraction of the added amines to fresh/frozen fish tissue. This finding could
      indicate that current extraction procedures may cause biogenic amines to be
      underestimated.

PMID- 18727537
TI  - Simultaneous determination of free carnitine and total choline by liquid
      chromatography/mass spectrometry in infant formula and health-care products:
      single-laboratory validation.
AB  - A single-laboratory validation study was conducted for a liquid
      chromatographic/mass spectrometric (LCIMS) method for the simultaneous
      determination of the free carnitine and total choline in milk-based infant
      formula and health-care products. The sample preparation used for both carnitine
      and choline was adapted from AOAC Official Method 999.14, with an acidic and
      enzymatic hydrolysis of esterified forms of choline. Carnitine and choline were
      quantified by ion-pair chromatography with single-quadrupole MS detection, using
      their respective deuterated internal standards. The repeatability relative
      standard deviation was < or =2.5 and 2.1%, respectively, for carnitine and
      choline. The intermediate reproducibility relative standard deviation was <4.7
      and 2.4%, respectively, for carnitine and choline. The ranges of the average
      product-specific recoveries were 92-98 and 94-103%, respectively, for carnitine
      and choline. Choline concentration determined in infant formula reference
      material SRM 1846 was in agreement with the reference value. The proposed method
      was compared with the enzymatic methods for a range of products; good correlation
      (r = 0.99) was obtained, although a significant bias was observed for both
      analytes. The method, with a short chromatographic run time (7 min), is
      convenient for routine analysis to enhance analytical throughput and is a good
      alternative to enzymatic assays.

PMID- 18727538
TI  - Determination of vitamin B12 in food products by liquid chromatography/UV
      detection with immunoaffinity extraction: single-laboratory validation.
AB  - A fast and simple method to determine vitamin B12 in foods is presented. The
      method allows, in addition to the determination of added cyanocobalamin, the
      determination of natural vitamin B12 forms, making it also applicable to
      nonfortified products, especially those that are milk-based. Vitamin B12 is
      extracted 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 liquid chromatography with UV detection (361 nm).
      The method has been validated in analyses of a large range of products: milk- and
      soy-based infant formulas, cereals, cocoa beverages, health care products, and
      polyvitamin premixes. The method showed appropriate performance characteristics:
      linear response over a large range of concentrations, recovery rates of 100.8 +/-
      7.5% (average +/- standard deviation), relative standard deviation of
      repeatability, RSDr, of 2.1%, and intermediate reproducibility, RSDiR, of 4.3%.
      Limits of detection and quantitation were 0.10 and 0.30 microg/100 g,
      respectively, and correlation with the reference microbiological assay was good
      (R2 = 0.9442). The proposed method is suitable for the routine determination of
      vitamin B12 in fortified foods, as well as in nonfortified dairy products. It can
      be used as a faster, more selective, and more precise alternative to the
      classical microbiological determination.

PMID- 18727539
TI  - A novel photometric method for evaluation of the oxidative stability of virgin
      olive oils.
AB  - The Oxitester method, a novel, simple, and fast photometric method for the
      evaluation of the antioxidant capacity of olive oils, was validated and compared
      to the official oil stability index (Rancimat) method. The Oxitester method
      appeared to be a good alternative to the Rancimat method with adequate
      correlation for a wide range of virgin olive oil samples, including extrissima
      virgin olive oils (correlation coefficient 0.88), and extra virgin olive oils of
      increased acidity (free fatty acids >0.45%, correlation coefficient 0.89). Other
      quality factors (flavor, free fatty acids content, specific absorbance at 270 and
      232 nm, peroxide value, and content of oleic, linoleic, and linolenic acids) were
      also measured and correlated to the antioxidant capacity values of the Oxitester
      and Rancimat methods. The Oxitester method, in contrast to the Rancimat method,
      was indicative of the flavor characteristics of the olive oils and the content of
      linolenic acid.

PMID- 18727540
TI  - Determination of moisture and fat in meats by microwave and nuclear magnetic
      resonance analysis: collaborative study.
AB  - Ten laboratories participated in a collaborative study to determine the total
      moisture and fat in raw and processed meat products by microwave drying and
      nuclear magnetic resonance (NMR) spectroscopy. Meat products were prepared
      following the AOAC Method and analyzed using CEM Corp.'s SMART Trac Moisture and
      Fat Analysis system. SMART Trac provides moisture results by measuring the weight
      loss on drying by microwave energy. The dried sample is then analyzed by NMR
      spectrometry for fat content. Moisture and fat results are displayed and reported
      by the SMART Trac as a percentage (g/100 g). Microwave drying is an AOAC-approved
      reference method (Method 985.14), Moisture in Meat and Poultry Products. NMR
      spectrometry is a secondary technique used to determine the concentration of
      various constituents in biological, organic, or chemical samples. The study
      design was based on Youden's matched pair principle for collaborative tests. For
      the purposes of this study, 10 laboratories each tested 10 Youden matched pairs,
      for a total of 20 samples. The study samples represented a range of products
      processed daily in plant operations. Included were raw meat samples (beef, pork,
      chicken, and turkey) as well as processed meats (beef hot dog, pork sausage, and
      ham). The total moisture content of the undiluted samples, as received for the
      purposes of this study, was determined by AOAC Method 950.46 and ranged from
      54.03 to 74.99%. The total fat content of the undiluted samples was determined by
      AOAC Method 960.39 and ranged from 1.00 to 29.79%. Statistical analysis of study
      results for total moisture yielded a relative standard deviation for
      repeatability (RSDr) range of 0.14 to 0.95% and a relative standard deviation for
      reproducibility (RSDR) range of 0.26 to 0.95%. Statistical analysis for total fat
      yielded similar RSDr and RSDR range of 0.74 to 4.08%. Results for turkey had
      higher RSDr and RSDR values, both at 12.6%, due to low fat content and possibly
      to the separation of the samples observed by some of the collaborators. Results
      demonstrate that microwave drying with NMR is a rapid, practical method providing
      results equivalent to AOAC Methods 950.46 (Forced Air Oven Drying) and 960.39
      (Soxhlet Ether Extraction) in raw and processed meat products.

PMID- 18727541
TI  - Fatty acid profile of Canadian dairy products with special attention to the trans
      octadecenoic acid and conjugated linoleic acid isomers.
AB  - Current scientific evidence indicates that consumption of industrial trans fatty
      acids (TFA) produced via partial hydrogenation of vegetable oils increases the
      risk of coronary heart disease. However, some studies have suggested that
      ruminant TFA, especially vaccenic acid (VA or 11t-18:1) and rumenic acid (RA or
      9c,11t-18:2), which is a conjugated linoleic acid (CLA) isomer, may have
      potential beneficial health effects for humans. To date, no concerted effort has
      been made to provide detailed isomer composition of ruminant TFA and CLA of
      Canadian dairy products, information that is required to properly assess their
      nutritional impacts. To this end, we analyzed the fatty acid profile of popular
      brands of commercial cheese (n = 17), butter (n = 12), milk (n = 8), and cream (n
      = 4) sold in retail stores in Ottawa, Canada, in 2006-2007 by silver nitrate thin
      layer chromatography and gas liquid chromatography. The average total TFA content
      of cheese, butter, milk, and cream samples were 5.6, 5.8, 5.8, and 5.5% of total
      fatty acids, respectively. VA was the major trans-octadecenoic acid (18:1) isomer
      in all the Canadian dairy samples with average levels of (as % total trans-18:1)
      33.9% in cheese, 35.6% in butter, 31.0% milk, and 30.1% in cream. The different
      dairy products contained very similar levels of CLA, which ranged from 0.5 to
      0.9% of total fat. RA was the major CLA isomer of all the dairy products,
      accounting for 82.4-83.2% of total CLA. There were no significant differences (P
      > 0.05) in the fatty acid profile between the 4 different dairy groups, which
      suggests lack of processing effects on the fatty acid profile of dairy fat.

PMID- 18727542
TI  - Modification of AOAC method 973.31 for determination of nitrite in cured meats.
AB  - A modification of AOAC Method 973.31 is proposed to improve the extraction
      efficiency of nitrite from cured meat samples and its subsequent quantification
      based on the diazotization-coupling reaction of sulfanilamide with N-(1
      naphthyl)ethylenediamine dihydrochloride (NED). The various experimental
      parameters were thoroughly investigated. A 5 g meat sample was mixed with 400 mL
      water; the pH of the mixture was adjusted to 5.5 +/- 0.3 and allowed to stand for
      2 h on a water bath at 80 degrees C, with occasional shaking for the complete
      extraction of nitrite. After quantitative filtration, an aliquot was mixed with
      chloroacetic-chloroacetate buffer, pH 1.80 +/- 0.05, sulfanilamide, and NED, and
      the absorbance of the resulting azodye was recorded at 540 nm against water as a
      reference. Following the recommended procedure, a linear calibration graph was
      obtained for up to 0.8 microg/mL NO2(-), with a correlation coefficient of 0.9996
      and a detection limit (based on the 3 Sb-criterion) of 5.6 ng/mL NO2(-). The
      proposed method was conveniently applied to various cured meat samples and was
      validated by comparison with the original AOAC method and by recovery experiments
      that gave quantitative results (94-98%) with convenient reproducibility.
      Statistical analysis of the analytical data could not detect any systematic error
      and revealed the high accuracy and precision of the proposed method.

PMID- 18727543
TI  - Purification of pediocin PA-1 by immunoaffinity chromatography.
AB  - A one-step purification procedure for purifying pediocin PA-1, a class IIa
      bacteriocin produced by Pediococcus acidilactici UL5, was developed based on
      column immunoaffinity chromatography with specific antipediocin PA-1 polyclonal
      antibodies coupled to cyanogen bromide-activated SepharoseTM. About 13.3
      microg/mL purified pediocin PA-1 was obtained from 15 mL P. acidilactici UL5
      culture supernatant, as measured by enzyme-linked immunosorbent assay. The
      specific activity and average recovery of the eluted pediocin PA-1 were about
      6602 AU/mg and 53.3%, respectively. This is the first report of successful
      purification of pediocin PA-1 by immunoaffinity using pediocin PA-1-specific
      polyclonal antibodies.

PMID- 18727544
TI  - Determining the efficacy of liquid sporicides against spores of Bacillus subtilis
      on a hard nonporous surface using the quantitative three step method:
      collaborative study.
AB  - A collaborative study was conducted to validate the quantitative Three Step
      Method (TSM), a method designed to measure the performance of liquid sporicides
      on a hard nonporous surface. Ten laboratories agreed to participate in the
      collaborative study; data from 8 of 10 participating laboratories were used in
      the final statistical analysis. The TSM uses 5 x 5 x 1 mm glass coupons
      (carriers) upon which spores have been inoculated and which are introduced into
      liquid sporicidal agent contained in a microcentrifuge tube. Following exposure
      to a test chemical and a neutralization agent, spores are removed from carriers
      in 3 fractions: passive removal (Fraction A), sonication (Fraction B), and gentle
      agitation (Fraction C). Liquid from each fraction is serially diluted and plated
      on a recovery medium for spore enumeration. Control counts are compared to the
      treated counts, and the level of efficacy is determined by calculating the log10
      reduction (LR) of spores. The main statistical goals were to evaluate the
      repeatability and reproducibility of the LR values, to estimate the components of
      variance for LR, and to assess method responsiveness. AOAC Method 966.04-Method
      II was used as a reference method. The scope of the validation was limited to
      testing liquid formulations against spores of Bacillus subtilis, a surrogate for
      virulent strains of B. anthracis, on a hard nonporous surface (glass). The test
      chemicals used in the study were sodium hypochlorite, a combination of peracetic
      acid and hydrogen peroxide, and glutaraldehyde. Each test chemical was evaluated
      at 3 levels of presumed efficacy: high, medium, and low. Three replications were
      required. The TSM was validated as it successfully met the statistical parameters
      for quantitative test methods. Satisfactory validation parameters, such as the
      repeatability standard deviation (Sr) and reproducibility standard deviation
      (SR), were obtained for control carrier counts and LR values. Both the TSM and
      the reference method were responsive to the efficacy levels of the test
      chemicals. For the 72 total TSM tests conducted, the mean (+/- standard error of
      the mean) log density of spores per control carrier was 6.86 (+/- 0.08); the Sr
      and SR were low at 0.15 and 0.27, respectively. Across the range of test
      chemicals, the Sr and SR estimates associated with LR were also acceptably low.
      The Sr ranged from 0.17 to 0.72 and the SR ranged from 0.34 to 1.43. Overall, the
      Sr and SR estimates associated with the efficacy data were within the ranges
      published for other quantitative methods and meet the performance characteristics
      necessary for validation.

PMID- 18727545
TI  - Trace element profile of a wild edible mushroom (Suillus granulatus).
AB  - Seventeen elements, Al, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Ni, P, Pb, V,
      and Zn (macroelements and trace elements) were investigated by Atomic
      Spectrometries on a particular wild edible mushroom collected in the central
      region of Argentina during 2 different years in the same season. The metal
      content profile in Suillus granulatus samples is given. The found quantities of
      Na, K, Ca, Mg, Fe, P, V, and Al were 0.40, 10.84, 0.48, 0.30, 0.57, 4.24, 0.18,
      and 1.23 g/kg dry weight, respectively. The levels of Li, Cu, Zn, Cd, Co, Ni, Cr,
      and Mn were 0.98, 23.02, 22.30, 0.26, 0.16, 1.17, 0.90, and 28.75 mg/kg dry
      weight, respectively. Pb was not detected at the investigated levels. The results
      indicate that the levels of metals in the analyzed samples are not considered to
      be a health risk. In order to demonstrate the validity of our method, a recovery
      study was performed with acceptable results.

PMID- 18727546
TI  - Proficiency testing program for the determination of total arsenic, cadmium, and
      lead in seawater shrimp.
AB  - The proficiency testing (PT) program for 97 worldwide laboratories for
      determining total arsenic, cadmium, and lead in seawater shrimp under the
      auspices of the Asia-Pacific Laboratory Accreditation Cooperation (APLAC) is
      discussed. The program is one of the APLAC PT series whose primary purposes are
      to establish mutual agreement on the equivalence of the operation of APLAC member
      laboratories and to take corrective actions if testing deficiencies are
      identified. Pooled data for Cd and Pb were normally distributed with
      interlaboratory variations of 21.9 and 34.8%, respectively. The corresponding
      consensus mean values estimated by robust statistics were in good agreement with
      those obtained in the homogeneity tests. However, a bimodal distribution was
      observed from the determination of total As, in which 14 out of 74 participants
      reported much smaller values (0.482-6.4 mg/kg) as compared with the mean values
      of 60.9 mg/kg in the homogeneity test. The use of consensus mean is known to have
      significant deviation from the true value in bi- or multimodal distribution.
      Therefore, the mode value, a better estimate of central tendency, was chosen to
      assess participants' performance for total As. Estimates of the overall
      uncertainty from participants varied in this program, and some were recommended
      to acquire more comprehensive exposure toward important criteria as stipulated in
      ISO/IEC 17025.

PMID- 18727547
TI  - Determination of copper in water and plant samples by flame atomic absorption
      spectrometry after preconcentration on octadecyl silica membrane disks modified
      with a recently synthesized Schiff's base.
AB  - A simple, selective, reliable, and sensitive method for the determination of
      trace amounts of CU2+ ions in aqueous samples is proposed. The Cu2+ ions are
      adsorbed quantitatively during the passage of aqueous samples through an
      octadecyl (C18) silica membrane disk modified by a symmetrical tetradentate
      Schiff base ligand, N,N'-bis(4-phenylazo salicylaldimine) 3-chloro-1,2
      phenylenediamine (H2L). The retained Cu2+ ions were then stripped from the disk
      by elution with the minimal amount of nitric acid solution and determined by
      flame atomic absorption spectrometry. Various parameters, such as the effect of
      pH, flow rate, type and amount of eluent, and the effects of various cationic
      interferences on the recovery of ions were studied. The proposed method permitted
      large enrichment factors (about 550 and higher). The limit of detection of the
      method was 1.5 x 10(-2) microg/L. The use of the same disk modified with 6 mg H2L
      for at least 30 times showed no change in the recovery of Cu2+ ions. The accuracy
      of the method was confirmed by determination of Cu2+ ions in standard samples
      [National Institute of Environmental Studies (NIES) No. 2 and Nippon Keikinzoku
      Kogyo (NKK) No. 920]. The results demonstrated good agreement with certified
      values.

PMID- 18727548
TI  - A rapid and easy multiresidue method for the determination of pesticide residues
      in vegetables, fruits, and cereals using liquid Chromatography/tandem mass
      spectrometry.
AB  - The applicability of a rapid and easy multiresidue method for determination of
      pesticide residues in agricultural products by using liquid chromatography/tandem
      mass spectrometry (LC/MS/MS) was examined. Pesticide residues were extracted with
      acetonitrile in a disposable tube using a homogenizer, followed by salting out
      with anhydrous magnesium sulfate and sodium chloride. The extract was purified
      with a double-layered cartridge column (graphite carbon black/primary-secondary
      amine silica gel). After removal of the solvent, the extract was resolved in
      methanol-water and analyzed with LC/MS/MS. Recovery tests of 99 pesticide
      residues from 7 agricultural products were performed at 20 and 100 ng/g.
      Throughout all of the agricultural products tested, 47 pesticides exhibited
      satisfactory recoveries (70-120%) and relative standard deviations (<20%) at both
      concentrations. The time for processing of 12 samples to test solutions was
      approximately 2-3 h. This method could be useful for determination of pesticide
      residues in agricultural products.

PMID- 18727550
TI  - Accurate methodology for amino acids and bioactive peptides in functional foods
      and dietary supplements for assessing protein adequacy and health effects.

PMID- 18727549
TI  - Evaluation of a method for determining concentrations of isoeugenol, an AQUI-S
      residue, in fillet tissue from freshwater fish species.
AB  - AQUI-S is a fish anesthetic/sedative that is approved for use in a number of
      countries throughout the world and has the potential for use in the United
      States. The active ingredient in AQUI-S is isoeugenol. A method for determining
      isoeugenol concentrations in edible fillet tissue is needed for regulatory
      purposes, including surveillance and potential use in studies fulfilling human
      food safety data requirements if U.S. Food and Drug Administration approval is
      pursued. A method was developed and evaluated for determining isoeugenol
      concentrations in fillet tissue using relatively common procedures and equipment.
      The method produced accurate and precise results with fillet tissue from 10
      freshwater fish species. The percentage of isoeugenol recovered from samples
      fortified with isoeugenol at nominal concentrations of 1, 50, and 100 microg/g
      for all species was always >80 and <97%. Within-day precision for samples
      fortified at those same concentrations was < or =10%, and day-to-day precision
      was < or =4.0%. Method precision with fillet tissue containing biologically
      incurred isoeugenol was < or =8.1%. There were no or minimal chromatographic
      interferences in control fillet tissue extracts from 9 of the 10 species. The
      method detection limits for all but one species ranged from 0.004 to 0.014
      microg/g, and the quantitation limits ranged from 0.012 to 0.048 microg/g.

PMID- 18727551
TI  - Need for accurate and standardized determination of amino acids and bioactive
      peptides for evaluating protein quality and potential health effects of foods and
      dietary supplements.
AB  - Accurate standardized methods for the determination of amino acid in foods are
      required to assess the nutritional safety and compositional adequacy of sole
      source foods such as infant formulas and enteral nutritionals, and protein and
      amino acid supplements and their hydrolysates, and to assess protein claims of
      foods. Protein digestibility-corrected amino acid score (PDCAAS), which requires
      information on amino acid composition, is the official method for assessing
      protein claims of foods and supplements sold in the United States. PDCAAS has
      also been adopted internationally as the most suitable method for routine
      evaluation of protein quality of foods by the Food and Agriculture
      Organization/World Health Organization. Standardized methods for analysis of
      amino acids by ion-exchange chromatography have been developed. However, there is
      a need to develop validated methods of amino acid analysis in foods using liquid
      chromatographic techniques, which have replaced ion-exchange methods for
      quantifying amino acids in most laboratories. Bioactive peptides from animal and
      plant proteins have been found to potentially impact human health. A wide range
      of physiological effects, including blood pressure-lowering effects, cholesterol
      lowering ability, antithrombotic effects, enhancement of mineral absorption, and
      immunomodulatory effects have been described for bioactive peptides. There is
      considerable commercial interest in developing functional foods containing
      bioactive peptides. There is also a need to develop accurate standardized methods
      for the characterization (amino acid sequencing) and quantification of bioactive
      peptides and to carry out dose-response studies in animal models and clinical
      trials to assess safety, potential allergenicity, potential intolerance, and
      efficacy of bioactive peptides. Information from these studies is needed for
      determining the upper safe levels of bioactive peptides and as the basis for
      developing potential health claims for bioactive peptides. This information is,
      in turn, needed by regulatory agencies for developing appropriate policy and
      regulations on adding these substances to foods and for determining if health
      claims are scientifically substantiated.

PMID- 18727552
TI  - Available lysine in foods: a brief historical overview.
AB  - A brief historical overview is presented on the development of the science
      addressing lysine bioavailability in foods. Early observations that dietary
      protein utilization did not always correlate with gross amino acid composition
      led to an understanding that the amino acid lysine, in particular, can be easily
      damaged during food processing. Conventional amino acid analysis, involving a
      strong acid hydrolysis step, can lead to a significant degree of overestimation
      of lysine in processed foods. More recently, it has been found that not only food
      lysine content values but also estimates of lysine digestibility and digestible
      lysine contents may be erroneous. Estimates of absorbed (true ileal digestible)
      reactive lysine are accurate measures of available lysine. Technically, bioassays
      such as the slope-ratio assay determine utilized rather than available lysine.

PMID- 18727553
TI  - Determination of sulfur amino acids in foods as related to bioavailability.
AB  - During the processing of feedstuffs and foods, methionine can be oxidized to
      methionine sulfoxide and methionine sulfone, and cysteine can be oxidized to
      cysteic acid. Methionine sulfone and cysteic acid are nutritionally unavailable,
      but methionine sulfoxide can be utilized, at least to some degree. The degree of
      utilization depends on the levels of methionine, cysteine, and methionine
      sulfoxide in the diet, but there is no consensus in the literature on the
      quantitative impact of these dietary constituents on methionine sulfoxide
      utilization. Methionine and cysteine are most often determined after quantitative
      oxidation to methionine sulfone and cysteic acid, respectively, using performic
      acid oxidation prior to hydrolysis. However, this method may overestimate the
      methionine content of processed foods, as it will include any methionine
      sulfoxide and methionine sulfone present. A selection of analytical methods has
      been developed to allow the separate determination of the 3 oxidized forms of
      methionine, the merits of which are discussed in this review. An additional
      consideration for determining methionine and cysteine bioavailability is that not
      all dietary methionine and cysteine is digested and absorbed from the small
      intestine. Selected methods designed to determine the extent of digestion and
      absorption are discussed. Finally, a concept for a new assay for determining
      methionine bioavailability, which includes determining the digestibility of
      methionine and methionine sulfoxide as well as the utilization of methionine
      sulfoxide, is presented.

PMID- 18727554
TI  - Bioactive peptides.
AB  - Peptides with biological activities, released during gastrointestinal digestion
      or food processing, play an important role in metabolic regulation and
      modulation, suggesting their potential use as nutraceuticals and functional food
      ingredients for health promotion and disease risk reduction. Many studies have
      reported that peptides from various food sources possess bioactivities, including
      antihypertensive, antioxidant, anticancer, antimicrobial, and opioid activities
      as well as immunomodulatory and cholesterol-lowering effects. More studies are
      being performed exploring the sources, bioavailabilities, and possible
      physiological/functional properties and the mechanisms of action of bioactive
      peptides. Technological approaches in terms of peptide preparation, purification,
      and characterization have also been investigated.

PMID- 18727555
TI  - Lunasin: a novel cancer preventive seed peptide that modifies chromatin.
AB  - Lunasin is a novel cancer preventive peptide whose efficacy against chemical
      carcinogens and oncogenes has been demonstrated in mammalian cells and a skin
      cancer mouse model. In contrast, constitutive expression of the lunasin gene in
      mammalian cells leads to arrest of cell division and cell death. Isolated and
      characterized in soy, lunasin peptide is also documented in barley and wheat and
      is predicted to be present in many more seeds because of its possible role in
      seed development. Initial studies show that lunasin is bioavailable in mice when
      orally ingested. Lunasin internalizes into mammalian cells within minutes of
      exogenous application, and localizes in the nucleus after 18 h. It inhibits
      acetylation of core histones in mammalian cells but does not affect the growth
      rate of normal and established cancer cell lines. An epigenetic mechanism of
      action is proposed whereby lunasin selectively kills cells being transformed or
      newly transformed cells by binding to deacetylated core histones exposed by the
      transformation event, disrupting the dynamics of histone acetylation
      deacetylation.

PMID- 18727556
TI  - Analysis of soybean protein-derived peptides and the effect of cultivar,
      environmental conditions, and processing on lunasin concentration in soybean and
      soy products.
AB  - Soybean, an important source of food proteins, has received increasing interest
      from the public because of its reported health benefits. These health benefits
      are attributed to its components, including isoflavones, saponins, proteins, and
      peptides. Lunasin, Bowman-Birk inhibitor, lectin, and beta-conglycinin are some
      of the biologically active peptides and proteins found in soybean. This article
      provides a comprehensive review on the recently used techniques in the analysis
      and characterization of food bioactive peptides, with emphasis on soybean
      peptides. The methods used to isolate and purify lunasin from defatted soybean
      flour were ion-exchange chromatography, ultrafiltration, and gel filtration
      chromatography. The identity of lunasin was established by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, Western blot, matrix-assisted laser
      desorption ionization-time of flight, and liquid chromatography. The results on
      the effect of soybean cultivar and environmental factors on lunasin concentration
      are also reported. The highest lunasin concentration, 11.7 +/- 0.3 mg/g flour,
      was found in Loda soybean cultivar grown at 23 degrees C; the lowest
      concentration, 5.4 +/- 0.4 mg/g flour, was found in Imari soybean cultivar grown
      at 28 degrees C. Lunasin concentration was affected by cultivar-temperature,
      cultivar-soil moisture, and cultivar-temperature-soil moisture interactions. The
      variation on lunasin concentration suggests that its content can be improved by
      breeding, and by optimization of growing conditions. In summary, bioactive
      peptides can be accurately identified and quantified by using different
      techniques and conditions. In addition, lunasin concentration in soybean depends
      mainly on cultivar and to some extent on environmental factors, particularly
      temperature. Lunasin concentration in soy products was also affected by
      processing conditions.

PMID- 18727557
TI  - Determination of nutritional and bioactive properties of peptides in enzymatic
      pea, chickpea, and mung bean protein hydrolysates.
AB  - Within the primary structure of many pea and mung bean proteins are peptide
      sequences that can potentially be used in the formulation of therapeutic products
      for the treatment and prevention of human diseases. However, these peptide
      sequences need protease treatments before they can be released free of the parent
      proteins. Unlike chemical hydrolysis, enzymatic treatment enables more efficient
      tailoring of peptide products without formation of toxic by-products or
      destruction of amino acids. This review provides information on current methods
      that have been used to convert inactive pea and mung bean proteins into bioactive
      peptides. It focuses on 3 main bioactive properties, such as inhibitions of (1)
      angiotensin converting enzyme (ACE) activity; (2) calmodulin (CaM)-dependent
      enzymes; and (3) copper-chelating activity. ACE is an established marker for
      hypertension, high levels of some CaM-dependent enzymes are risk factors for
      various human diseases including cancer and Alzheimer's disease, and high
      vascular copper concentrations may potentiate atherosclerosis. Also reviewed are
      the production and evaluation of activity of hypoallergenic peptides that may
      offer protection against anaphylactic reactions. The 3 main proteins discussed
      are chickpea, mung bean, and field pea.

PMID- 18727558
TI  - Biopharming to increase bioactive peptides in rice seed.
AB  - The production of high-value pharmaceutical proteins and peptides in transgenic
      plants is an attractive and economically feasible alternative to conventional
      mammalian cell, yeast, and bacterial systems. In contrast to vegetative tissues,
      rice seeds allow higher accumulation of recombinant proteins and long-term stable
      storage. Rice is not only consumed as a staple food by a majority of the world's
      population, but is also used as a model monocot for biotechnological
      manipulation. Daily oral consumption of transgenic rice seeds that accumulate
      high concentrations of food-derived or synthetic bioactive peptides can be
      expected to provide a safe, reliable, and consistent oral delivery system that
      would contribute to the promotion of human health care.

PMID- 18727559
TI  - BIOPEP database and other programs for processing bioactive peptide sequences.
AB  - This review presents the potential for application of computational tools in
      peptide science based on a sample BIOPEP database and program as well as other
      programs and databases available via the World Wide Web. The BIOPEP application
      contains a database of biologically active peptide sequences and a program
      enabling construction of profiles of the potential biological activity of protein
      fragments, calculation of quantitative descriptors as measures of the value of
      proteins as potential precursors of bioactive peptides, and prediction of bonds
      susceptible to hydrolysis by endopeptidases in a protein chain. Other bioactive
      and allergenic peptide sequence databases are also presented. Programs enabling
      the construction of binary and multiple alignments between peptide sequences, the
      construction of sequence motifs attributed to a given type of bioactivity,
      searching for potential precursors of bioactive peptides, and the prediction of
      sites susceptible to proteolytic cleavage in protein chains are available via the
      Internet as are other approaches concerning secondary structure prediction and
      calculation of physicochemical features based on amino acid sequence. Programs
      for prediction of allergenic and toxic properties have also been developed. This
      review explores the possibilities of cooperation between various programs.

PMID- 18727560
TI  - Application of mass spectrometry to the characterization and quantification of
      food-derived bioactive peptides.
AB  - Biologically active peptides are of particular interest in food science and
      nutrition because they have been shown to play different physiological roles,
      including antihypertensive, opioid, antimicrobial, and immunostimulating
      activities. Because these peptides are generated by protein hydrolysis or
      fermentation, they can represent only minor constituents in a highly complex
      matrix and therefore, identification of biologically active peptides in food
      matrixes is a challenging task in food technology. In this context, mass
      spectrometry (MS) has developed into a necessary tool to assess quality and
      safety of food and, more recently, to determine the presence and behavior of
      functional components such as these bioactive peptides. This review highlights
      the existing methods based on MS to identify, characterize, and quantify food
      derived biologically active peptides, taking into account the different
      ionization sources used for the analysis of these high-value food components. The
      quantitative determination of bioactive peptides in food products or biological
      fluids is also discussed.

PMID- 18727561
TI  - Identification of food-derived bioactive peptides in blood and other biological
      samples.
AB  - Recent studies have demonstrated the presence of food-derived peptides in human
      blood after ingestion of enzymatic hydrolysates of food proteins, while most
      peptides in food are degraded into amino acids during digestion and absorption.
      To capture and clarify the food-derived peptides in blood, solid-phase extraction
      (SPE) using a mini-spin column packed with a strong cation exchanger was
      developed. This technique allows the use of a nonvolatile acid such as
      trichloroacetic acid, a strong protein denaturant, for the deproteinizing
      procedure. To improve resolution of hydrophilic peptide and increase specificity
      and sensitivity in the detection of peptide by reversed-phase high-performance
      liquid chromatography (RP-HPLC) after subfractionation by size-exclusion
      chromatography (SEC), peptides are derivatized with phenyl isothiocyanate. The
      resultant phenyl thiocarbamyl (PTC)-peptides can be resolved with high resolution
      and sensitivity by RP-HPLC. By comparing chromatograms of PTC derivatives from
      blood before and after ingestion of a peptide sample, food-derived peptide can be
      detected. The isolated PTC-peptide can be applied to a peptide sequencer based on
      the Edman degradation reaction.

PMID- 18727562
TI  - Comparison of digestibility and quality of intact proteins with their respective
      hydrolysates.
AB  - Quality of proteins depends on their composition in essential amino acids and on
      the availability of amino acids. Great interest has been shown in the role played
      by hydrolysates of proteins in clinical diets for pathologies with reduced
      absorptive capacity and food allergies caused by intact protein epitopes. Milk
      proteins are the most important protein source used in the development of protein
      hydrolysates designed for nutritional support of patients. Several studies have
      shown that casein and whey hydrolysates have a composition in amino acids
      equivalent to that in native milk proteins and that digestibility is similar or
      better. Among plant proteins, soy is the major source of hydrolysates. Soy
      hydrolysates are also used in infant formulas. Plant hydrolysates have good
      functional properties and a nutritional quality similar to that of starting
      material. Some technical improvements in production of hydrolysates, particularly
      for plants, are nevertheless necessary to improve product palatability.

PMID- 18727570
TI  - [Home care services, a bridge between the hospital and home].

PMID- 18727569
TI  - [Urinary catheterization in the elderly patient].

PMID- 18727571
TI  - [Art therapist in a medicalized nursing home. Interview by Elizabeth Rogez].

PMID- 18727572
TI  - [Infectious risk in geriatrics].

PMID- 18727573
TI  - [Different dimensions of care for the elderly patient].

PMID- 18727574
TI  - [Artistic expression, a tool for helping elderly persons].

PMID- 18727575
TI  - [Music therapy, a therapeutic tool for communicating with the elderly demented
      patient].

PMID- 18727576
TI  - [The hobby workshop for the elderly, a living and separate space].

PMID- 18727577
TI  - [The bath, a therapeutic space].

PMID- 18727578
TI  - [A new approach to the daily toilette of the elderly patient].

PMID- 18727579
TI  - [Individual autonomy plan for the daily toilette, a tool to reappropriate the
      nursing function].

PMID- 18727580
TI  - [4/6--The social life auxiliary].

PMID- 18727581
TI  - [1/8--Information and consent in the elderly person].

PMID- 18727582
TI  - [Chronic skin ulcers].

PMID- 18727583
TI  - [4/6. Management of the buccal candidiasis].

PMID- 18727590
TI  - [Growing up with a difference].

PMID- 18727591
TI  - [Children are always different].

PMID- 18727592
TI  - [Helping the intellectually precocious child].

PMID- 18727593
TI  - [Mainstreaming mentally and psychologically handicapped children].

PMID- 18727594
TI  - [Proprioception management of dyslexic children].

PMID- 18727595
TI  - [Caring for the child with a chronic illness and his family].

PMID- 18727596
TI  - [Admitting and caring for migrant children and their parents].

PMID- 18727597
TI  - [Admitting the adolescent in consultation].

PMID- 18727598
TI  - [Pneumatosis intestinalis; no disease, but a symptom].
AB  - In three patients, men aged 77, 83 and 69 years, pneumatosis intestinalis was
      detected during CT for abdominal pain occurring in the first patient after an
      aortic stent had been placed, and during laparotomy because of ileus in the
      latter two patients. The first patient underwent removal of an ischaemic
      intestinal segment but died later due to infection around the prosthesis. The
      other two patients recovered after conservative therapy. Pneumatosis intestinalis
      is defined as the presence of gas in the wall of the gastrointestinal tract.
      Often it is detected by accident during abdominal radiographic examination or
      laparotomy. Pneumatosis intestinalis is a symptom and has been found in a wide
      variety of diseases. The clinical condition of the patient and the underlying
      disease determine the clinical significance of pneumatosis intestinalis and the
      therapy. The main issue is whether surgical intervention is necessary because of
      intestinal ischaemia or perforation.

PMID- 18727599
TI  - [A place for SSRIs in the treatment of severely depressed children and
      adolescents].
AB  - Although in the past there were objections against the use of selective serotonin
      reuptake inhibitors (SSRIs) for the treatment of depression in children and
      adolescents, recent studies have shown that SSRIs, in particular fluoxetine, are
      effective against depression in this age group. Cognitive behavioural therapy has
      a questionable effect in children and adolescents with severe depression. Other
      unequivocally effective treatment options are not available. More suicidal
      behaviour was reported in children and adolescents using sertraline or
      venlafaxine, but fluoxetine did not clearly enhance this behaviour. Children with
      severe depression or a depression not responding to psychological therapy can be
      treated with SSRIs. Fluoxetine is the treatment of first choice.

PMID- 18727600
TI  - [Treatment of hypertension in people over 80 years should not be discontinued].
AB  - The 'Hypertension in the very elderly trial' (HYVET) was designed to answer the
      question whether antihypertensive treatment reduces strokes (both fatal and non
      fatal strokes) without increasing total mortality. A total of 3845 patients were
      assigned to active treatment or placebo. About 90% had a history of hypertension,
      65% of which were being treated. At the start of the study all antihypertensive
      treatment was stopped and the subjects were randomized to either indapamide 1.5
      mg with or without perindopril 2-4 mg or to identical looking placebo. After
      about 2 years the trial was discontinued for ethical reasons as there was less
      death from any cause in the intervention group. Blood pressure decreased with
      30/13 mmHg in the treatment versus 15/7 mmHg in the placebo group. There was a
      30% decrease of all strokes (p = 0.06) but a significant reduction in fatal
      strokes (p < 0.05). Unexpected was the 21% reduction in all-cause mortality (p <
      0.02). The 23% reduction in the rate of cardiovascular death was not significant
      (p < 0.06). Heart failure and total cardiovascular events decreased (p < 0.001).
      There were fewer adverse effects in the treatment group (p = 0.001). In our
      opinion HYVET proves that antihypertensive medication should not be stopped when
      patients pass the age of 80 years. However, it remains to be established whether
      treatment should be started in new patients who present themselves with
      hypertension above the age of 80 years.

PMID- 18727601
TI  - [Use of oral contraceptives and increased risk of cervical cancer].
AB  - A recently published meta-analysis and a large cohort study showed independently
      that use of oral contraceptives (OC) leads to an increased relative risk (RR) of
      cervical cancer. This RR increased with the duration of OC use and was 1.90 after
      5 years or more (95% CI: 1.69-2.13). The increased RR decreased after cessation
      of OC use and was normal again Io years later. Longstanding OC use enhances human
      papillomavirus (HPV) transcription and decreases HPV clearance, resulting in more
      frequent persistence of HPV, an increase of cervical intraepithelial neoplasia,
      and an increased RR of cervical cancer. The increase in cervical cancer by OC is,
      however, associated with a fully compensatory decrease in the incidence of other
      malignancies, in particular ovarian cancer and endometrial cancer. Based on these
      findings, there are no reasons to discourage the use of OC by women in the
      Netherlands.

PMID- 18727602
TI  - [Umbilical cord blood from an unrelated donor as source for stem cell
      transplantations in inborn errors of metabolism].
AB  - In certain inborn errors of metabolism, an allogeneic stem cell transplantation
      is able to prevent disease progression. This is only possible when the stem cell
      transplantation (SCT) is performed early in life, before cerebral involvement has
      occurred. In addition to bone marrow and peripheral blood, unrelated umbilical
      cord blood appears to be an effective stem cell source as well. Important
      advantages of umbilical blood as stem cell source are: the time between diagnosis
      and SCT can be considerably reduced; there is a greater chance of finding a
      suitable donor and the risk of graft-versus-host disease and viral transmission
      is decreased. By far the most common disease in the group of inborn metabolic
      errors for which SCTs are performed is Hurler's disease. In these patients, the
      percentage of successful transplantations is considerably higher after the use
      ofunrelated cord blood than when bone marrow or peripheral blood is used as a
      stem cell source. In addition, donor chimerism occurred significantly more often
      in those patients who had received unrelated umbilical cord blood. There are also
      potential disadvantages attached to the use of umbilical blood as stem cell
      source: the possibility of only one donation per donor and less adaptive immunity
      following umbilical blood SCT with an increased risk of reactivation of a
      previous viral infection. However, these disadvantages are less applicable to
      young children with inborn errors of metabolism. The improvement of
      transplantation techniques and the availability of this new stem cell source
      could improve the success rate of this procedure and consequently the prognosis
      of these severely affected patients.

PMID- 18727603
TI  - [Practical advice for travellers with immune disorders].
AB  - For patients with immune disorders, the risk of infection during travel depends
      on the cause and severity of the immune disorder and the type of travel.
      Immunocompromised travellers experience more severe effects of illness than those
      without immune disorders. Some risks can be reduced or avoided by taking adequate
      precautions and, in some cases, modifying travel plans. Ensuring adequate
      medication use during the trip requires careful planning prior to travel.
      Regarding vaccination, immunocompromised travellers may have an impaired ability
      to generate antibodies; live attenuated vaccines are often contraindicated. The
      treating physician must take a proactive role when an immunocompromised patient
      indicates that he or she plans to travel. Protocols developed by the Dutch
      National Coordination Centre for Travellers Health (LCR) provide practical advice
      regarding a number of situations. Provided that they are given proper
      individualised advice, there is little concrete evidence to suggest that these
      patients should not travel anywhere they wish.

PMID- 18727604
TI  - [Diagnostic image (383). A man with tenderness in the neck after trauma. Cervical
      thoracic dislocation].
AB  - A 62-year-old man had tenderness in the neck due to cervicothoracic dislocation
      after a fall from his bicycle.

PMID- 18727605
TI  - [Treatment of neonatal hypoglycaemia: more frequent latching onto the breast
      versus supplementary feeding with formula; retrospective study of patient files].
AB  - OBJECTIVE: To evaluate the effects of frequent latching versus supplementary
      feeding of breastfed infants with hypoglycaemia on blood glucose concentrations
      and breastfeeding. DESIGN: Retrospective study of patient files. METHOD: All
      breastfed infants born in the period of investigation (June 1st 2004-April 30th
      2005) by artificial or breech delivery were included. In the group with
      supplementary feeding (June 1st 2004 until December 12th 2004) mild neonatal
      hypoglycaemia, defined as glucose concentrations between 1.8 and 2.5 mmol/l, with
      symptoms, or between 1.3 and 1.7 mmol/l, without symptoms, was treated with
      supplementary feeding with formula. In the group with more frequent latching
      (December 13th 2004-April 30th 2005) mild neonatal hypoglycaemia (defined as
      glucose levels of 1.8-2.1 mmol/l) was treated with more frequent latching without
      supplementary feeding. The change in feeding policy (mid December 2004) was
      introduced because of excessive numbers of supplementary feedings, which
      jeopardized breastfeeding. Blood glucose determinations were carried out with the
      HemoCue B-glucose system. Risk factors for hypoglycaemia were listed, enabling
      the assessment of data of neonates who did not run an increased risk of
      hypoglycaemia, a kind of 'control group'. RESULTS: 232 newborn infants were
      included: 158 in the supplementary feeding group and 74 in the group with more
      frequent latching. In the supplementary feeding group, 63% (100/158) of the
      children developed hypoglycaemia, versus 55% (41/77) in the group with more
      frequent latching. The latter had lower blood glucose concentrations than the
      supplementary feeding group. This difference was only significant for infants
      without risk factors: the mean difference in lowest glucose concentration between
      supplementary feeding and more frequent latching in the group without risk
      factors was 0.50 mmol/L (SD: 0.69; 95% CI: 0.06-0.93; p = 0.03) versus 0.20
      mmol/l (SD: 0.79; 95% CI: -0.05-0.45; p = 0.14) in the group with risk factors.
      Supplementary feedings decreased by 39% (95% CI: 28-50). The number of infants
      discharged with breastfeeding only increased by 14% (95% CI: 2-26). Symptomatic
      hypoglycaemic episodes were not found in the group with supplementary feeding or
      in the group with more frequent latching. CONCLUSION: Frequent latching instead
      of supplementary (formula) feeding in infants with mild neonatal hypoglycaemia
      was associated with lower blood glucose concentrations but with higher
      percentages of breastfeeding only at discharge.

PMID- 18727606
TI  - [Cystic abnormalities of the pancreas: inflammatory pseudocyst or neoplasm].
AB  - A 79-year-old woman presented with complaints of upper abdominal pain, nausea and
      vomiting since a few days. Laboratory tests showed no abnormalities except for
      some indications of an inflammation. Based on the medical history, physical
      examination and findings from radiological examination, initially the diagnosis
      was 'chronic pancreatitis with formation ofa pseudocyst caused by alcohol abuse'.
      After one week the patient developed cholestatic liver function disorders with
      elevated serum pancreatic enzymes. A CT scan of the abdomen showed a dilated
      gallbladder and progression of the cystic lesion in the pancreatic head with
      compression of the distal common bile duct. An endoscopic retrograde
      cholangiopancreatography was performed and the findings fitted a diagnosis of an
      intraductal papillary mucinous neoplasm. Differentiation between an inflammatory
      or neoplastic origin of cystic lesions in the pancreas can be difficult. There is
      a risk ofmisdiagnosing a cystic neoplasm for a pseudocyst. This may lead to
      delays in making the correct diagnosis.

PMID- 18727607
TI  - [A 65-year-old patient with an odontoid fracture caused by 'headbanging'].
AB  - A 65-year-old woman who habitually made flexion-extension movements with her
      cervical vertebral column (so-called 'headbanging') was seen with complaints of
      the neck. X-rays of the neck revealed an odontoid fracture. Bone densitometry
      revealed lowered bone mineral density (osteopenia). The diagnosis was odontoid
      fracture due to headbanging, in the presence of osteopenia. Patient recovered
      after treatment with a neck collar worn for 6 months.

PMID- 18727608
TI  - [Post-mortem MRI in newborns when autopsy is not permitted].

PMID- 18727609
TI  - [Medicine is not gender-neutral: influence of physician sex on medical care].

PMID- 18727610
TI  - [A falsely reassuring cervical smear in adenocarcinoma of the external os].

PMID- 18727611
TI  - [A falsely reassuring cervical smear in adenocarcinoma of the external os].

PMID- 18727612
TI  - Antimicrobial prophylaxis against infective endocarditis before urological
      surgery.

PMID- 18727613
TI  - Signal transduction pathways of muscarinic receptor mediated activation in the
      newborn and adult mouse urinary bladder.
AB  - OBJECTIVE: To study the role of M(2) and M(3) muscarinic receptor subtypes,
      sources of activator Ca(2+), and mechanisms involved in increased force
      oscillations in muscarinic contractions in the bladders of newborn and adult
      mice, as in the adult bladder muscarinic M(3) receptors are considered to mediate
      the main part of bladder contraction, and this has not been established in the
      newborn bladder. MATERIALS AND METHODS: Bladder preparations from newborn (0-2
      days) and adult (10-12 weeks) mice were mounted for in vitro force registration
      and activated with carbachol and high-K(+) solution in the presence of M(3) (4
      DAMP 30 nM) or M(2) (methoctramine, 100 nM) receptor antagonists. Thapsigargin (1
      microm) or ryanodine (10 microm) were used to inhibit sarcoplasmic reticulum
      Ca(2+) release. L-NAME (300 microm) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1
      one (ODQ; 10 microm) were used to inhibit nitric oxide synthase and guanylyl
      cyclase, respectively. Gap-junction function was inhibited with by 18-beta
      glycyrrhetinic acid (18-beta-GA; 0.1-100 microm). Big-conductance (BK) and small
      conductance (SK) K(+) channels were inhibited by apamine and charybdotoxin (0.3
      microm), respectively. RESULTS: Concentration-response relations for carbachol in
      the presence of 4-DAMP and methoctramine showed that M(3) receptors are the main
      activating pathway also in the newborn bladder. Neither thapsigargin nor
      ryanodine influenced the muscarinic responses of the newborn and adult bladders.
      Carbachol-induced contractions were not influenced by L-NAME or ODQ. The 18-beta
      GA inhibited carbachol-induced contractions in both newborn and adult tissue in a
      similar manner. Apamine and charybdotoxin slightly increased the amplitude of the
      contractile responses. CONCLUSION: These results suggest that in the newborn
      mouse bladder, as in adult bladders, the M(3) muscarinic receptor subtype is
      mainly responsible for carbachol-induced contractile responses. The main
      mechanism for muscarinic receptor-induced activation is influx of Ca(2+) from the
      extracellular medium, and there seems to be no major contribution of Ca(2+)
      release from intracellular stores. The phasic contractile activity induced by
      carbachol in the newborn bladder is not influenced by gap junction inhibition and
      does not involve SK and BK channels.

PMID- 18727614
TI  - Metabolic and cardiovascular effects of androgen deprivation therapy.
AB  - Prostate cancer is the most common gender-specific malignancy in men in the USA.
      Androgen-deprivation therapy (ADT) is commonly used in the treatment of
      metastatic or recurrent prostate cancer. The use of ADT is increasing with the
      advocacy of adjuvant and neoadjuvant ADT for treating asymptomatic patients with
      locally advanced prostate cancer. Although the use of ADT has resulted in
      improved survival in men with advanced prostate cancer, ADT, with its resulting
      severe hypogonadism, causes profound metabolic side-effects. We comprehensively
      reviewed previous reports using Medline searches of English-language literature
      (1950 to the present), with the keywords 'hypogonadism', 'testosterone',
      'androgen deprivation therapy', 'hormonal treatment', 'prostate cancer',
      'diabetes', 'metabolic syndrome', and 'cardiovascular disease'. Men with prostate
      cancer who undergo long-term ADT are at greater risk of developing dyslipidaemia,
      insulin resistance, hyperglycaemia and metabolic syndrome. These metabolic and
      physiological changes are a direct result of the induced severe hypogonadism and
      might predispose patients to a greater risk of cardiovascular morbidity and
      mortality. There is a need for prospective studies aimed and designed to
      investigate the metabolic and cardiovascular adverse effects of ADT, and assess
      the benefit/risk ratio, especially in special populations such as diabetics.

PMID- 18727615
TI  - The use of capsaicin in loin pain-haematuria syndrome.
AB  - OBJECTIVE: To highlight the implications of the use of capsaicin in managing loin
      pain-haematuria syndrome (LPHS). PATIENTS AND METHODS: Between February 2002 and
      February 2007, three patients (one male and two females; mean age 31.7 years)
      with LPHS were managed with capsaicin and followed up for a period of 8-48
      months. All were diagnosed with LPHS after negative urological investigations
      including urine culture, urine cytology, renal tract ultrasonography, intravenous
      urography and flexible cystoscopy; and nephrological work-ups including normal
      blood pressure measurements, creatinine clearance, urinary protein estimation and
      serum urea/creatinine. Five original papers were reviewed in detail for this
      article. Including our own experience, a total of 52 (including five bilateral)
      cases of LPHS treated with capsaicin are reviewed. RESULTS: Our patients received
      a total of four capsaicin instillations producing an average duration of pain
      relief per instillation of 17 weeks. There was evidence of renal deterioration in
      one, while another had worsened symptoms. The third patient continued his pain
      management within the pain clinic. The former two patients eventually underwent
      nephrectomy for poor function and extreme symptoms. CONCLUSION: Intrarenal
      capsaicin at best produces only short-term pain relief in more than half of
      patients with LPHS. It produces significant side-effects, i.e. UTI, bladder pain,
      and in up to half of patients, deteriorating symptoms. Further loss of functional
      renal tissue and a nephrectomy rate of 20-67% should be weighed against the
      benefits. We have therefore abandoned its use in treating LPHS or renal pain, and
      recommend that patients should be adequately counselled on its potential side
      effects, including nephrotoxicity and increased nephrectomy rate.

PMID- 18727616
TI  - Extracorporeal shock wave lithotripsy in children: equivalent clearance rates to
      adults is achieved with fewer and lower energy shock waves.
AB  - OBJECTIVE: To compare the outcome, safety and efficiency of extracorporeal shock
      wave lithotripsy (ESWL) using an electromagnetic lithotripter for upper urinary
      tract stones in children and adults. PATIENTS AND METHODS: We retrospectively
      reviewed data over a 5-year period for patients with solitary, renal and upper
      ureteric stones measuring <2 cm in whom ESWL was the treatment method. Group A
      consisted of 44 children (mean [SD] age 5.9 [4.4] years) and group B of 562
      adults (mean [SD] age 40.9 [13.1] years). The number and energy of SWs used was
      not predetermined and was tailored until adequate fragmentation was achieved.
      Initial stone reassessment was performed at 48 h and monthly thereafter. The
      number of SWs, intensity of SWs, stone-free rate, auxiliary procedure rate, re
      treatment rate, complication rate and effectiveness quotient (EQ) were assessed
      in each group. RESULTS: The stone-free rate with ESWL was 84% in children and 87%
      in adults (P = 0.78). The EQ was 77% and 75% in children and adults, respectively
      (P = 0.56). The mean (sd) number of SWs and energy required per session was 950
      (349) and 11.83 (0.48) kV in children and 1262 (454) and 12.36 (0.34) kV in
      adults (P < 0.001). The re-treatment, auxiliary procedure and complication rates
      were similar in both groups. CONCLUSION: ESWL is as safe and effective in
      children as in adults for solitary renal and upper ureteric stones that are <2
      cm. Children required significantly fewer and lower energy SWs to achieve
      equivalent results.

PMID- 18727617
TI  - Outcomes of patients after aborted radical cystectomy for intraoperative findings
      of metastatic disease.
AB  - OBJECTIVES: To assess the clinical outcome of patients with bladder cancer who
      underwent attempted radical cystectomy (RC) with curative intent, but whose
      procedures were aborted due to intraoperative findings of metastatic disease, as
      the presence of metastatic disease at RC is associated with a poor prognosis and
      there are no data on the optimum management strategy in this situation. PATIENTS
      AND METHODS: In all, 248 consecutive patients with bladder cancer had attempted
      RC at one academic institution between 1994 and 2003. We retrospectively reviewed
      the records of 35 patients who had an aborted RC due to intraoperative findings
      of metastatic disease. The pathological characteristics, time to recurrence,
      overall survival, disease-specific survival, and suitability for adjuvant or
      salvage therapies were examined. RESULTS: Of the 35 patients who had an aborted
      RC for metastatic disease, 21 (60%) died from the disease within the study period
      (median time to cancer-specific death 26.4 months), 11 (31%) are alive with
      evidence of persistent disease or progression, and three (9%) are alive with no
      evidence of recurrence or progression. Seven patients had a salvage RC after
      successful adjuvant treatment, of whom three died from recurrent disease (at a
      mean of 46.5 months after initial exploration, 31.9 months after salvage RC), one
      is alive with bladder cancer recurrence to the rectum 10 months after salvage
      cystectomy, and three have no evidence of disease progression at a mean of 10
      months after salvage RC. CONCLUSIONS: The prognosis of patients who undergo an
      aborted attempt at curative RC due to intraoperative findings of metastatic
      disease is poor. Although a few patients might subsequently have salvage RC, many
      of these patients still have poor outcomes even if adjuvant treatments are used.
      When metastatic disease is discovered at RC, completing the cystectomy should be
      considered, although further studies are needed to show a clinical benefit.

PMID- 18727618
TI  - Prognostic variables to predict cancer-related death in incidental renal tumours.
AB  - OBJECTIVE: To identify, in a large multicentre series of incidental renal
      tumours, the key factors that could predict cancer-related deaths, as such
      tumours have a better outcome than symptomatic tumours and selected patients are
      increasingly being included in watchful-waiting protocols. PATIENTS AND METHODS:
      Data from 3912 patients were extracted from three international kidney-cancer
      databases. Age, gender, Eastern Cooperative Oncology Group (ECOG) performance
      status (PS), Tumour-Node-Metastasis (TNM) stage, tumour size, Fuhrman grade, and
      final pathology were recorded. Benign tumours and malignant lesions with
      incomplete information were excluded from final analysis. RESULTS: The mean (SD)
      age of the patients was 60.6 (12.2) years and the mean tumour size 5.5 (3.5) cm.
      Most tumours were malignant (90.2%) and of low stage (T1-T2, 71.7%) and low grade
      (G1-G2, 72.4%). There were nodal and distant metastases in 5.7% and 13% of the
      patients. In all, 525 (14.4%) patients died from cancer; in this group, tumours
      were >4 cm in 88.2% and had nodal or distant metastases in 20.2% and 49.3%,
      respectively. Multivariable analysis showed that tumour size >4 cm, ECOG PS
      >or=1, TNM stage and Fuhrman grade were independent predictors of cancer-related
      death. CONCLUSION: A significant proportion of incidental renal tumours can lead
      to the death of the patient. Standard prognostic variables for renal cell
      carcinoma appear to remain valid for this subset of patients. A watchful-waiting
      strategy should not be recommended if the tumour diameter is >4 cm, if biopsy
      confirms high-grade tumours, or if there is an impaired ECOG PS, or computed
      tomography findings suggest the presence of advanced T stage.

PMID- 18727619
TI  - Association of angiotensin I-converting enzyme gene polymorphisms with aspirin
      intolerance in asthmatics.
AB  - BACKGROUND: Aspirin-intolerant asthma (AIA) refers to the development of
      bronchoconstriction in asthmatic individuals following the ingestion of aspirin
      or other non-steroidal anti-inflammatory drugs (NSAIDs). Angiotensin I-converting
      enzyme (ACE), a membrane-bound peptidase present in the lung, plays a pivotal
      role in the metabolism of the endogenous peptides involved in the pathogenesis of
      asthma. METHODS: We screened a Korean asthma cohort (581 asthmatics including 81
      aspirin-intolerant asthmatics and 231 aspirin-tolerant asthmatics, and 181 normal
      controls) for four single nucleotide polymorphisms (SNPs; -262 A>T and -115 T>C
      in the 5'-flanking region and +5467 T>C [Pro450Pro] and+11860 A>G [Thr776Thr] in
      the coding region) and one ins/del (+21288 CT) in the ACE gene. RESULTS: None of
      the SNPs or haplotypes showed any association with the development of asthma, but
      they were significantly associated with the risk of AIA. Logistic regression
      indicated that the frequency of the rare alleles of -262 A>T and -115 T>C was
      higher in subjects with AIA than in subjects with aspirin-tolerant asthma (ATA)
      (P=0.003-0.01, P( corr)=0.015-0.05). Subjects homozygous for the rare alleles of 
      262 A>T and -115 T>C showed a greater decline in forced expiratory volume in 1 s
      (FEV(1)) after aspirin provocation than those homozygous for the common alleles
      (P<0.05). A luciferase reporter assay indicated that ACE promoters containing the
      rare -262 A>T allele possessed lower activity than did those containing the
      common allele (P=0.009). In addition, ACE promoters bearing the rare -115 T>C
      allele had no luciferase activity. DNA-protein binding assays revealed a band
      containing the ACE promoter region (including -262 A) and a protein complex.
      CONCLUSION: The -262 A>T polymorphism in the promoter of the ACE gene is
      associated with AIA, and the rare allele of -262 A>T may confer aspirin
      hypersensitivity via the down-regulation of ACE expression.

PMID- 18727620
TI  - Comment on: Nitric oxide evaluation in upper and lower respiratory tracts in
      nasal polyposis. Delclaux C, et al.

PMID- 18727621
TI  - Practice of venom immunotherapy in the United Kingdom: a national audit and
      review of literature.
AB  - BACKGROUND: Venom immunotherapy (VIT) is the only effective treatment for
      prevention of serious allergic reactions to bee and wasp stings in sensitized
      individuals. However, controversies exist relating to diagnosis, indications for
      treatment and treatment schedules. We audited current practice of VIT in the
      United Kingdom to evaluate adherence to international guidelines. METHODS: An
      online questionnaire was sent to all clinicians practising immunotherapy
      identified on the British Society of Allergy and Clinical Immunology website.
      Eighty-six questionnaires were sent and 53 responses (61.6%) were received. Of
      these, 48 (85%) carried out VIT at their centre. RESULTS: Skin prick tests (SPT)
      and serum venom-specific IgE (SSIgE) were equally preferred as first-line
      investigation. Fifty percent of the respondents perform intradermal tests if both
      SPT and SSIgE are negative. While 8% of respondents commence VIT in patients with
      negative SSIgE and a history of severe reaction, 57% prefer to repeat the tests
      in 6-12 months if serum tryptase is elevated. If the insect responsible is
      uncertain and SSIgE is detected against bee and wasp venoms, 22% of the
      respondents will desensitize to both while 32% initiate treatment against the
      venom with the higher SSIgE. A protocol of weekly up-dosing for 12 weeks is
      preferred for induction and only 25% of respondents have ever used rush or ultra
      rush protocols. Three years is thought to be optimum duration of VIT by most
      (56%). Eleven percent perform sting challenges at the end of treatment. Although
      47% measure SSIgE at the end of treatment, only 3% use these results as a basis
      for discontinuing VIT. CONCLUSION: Currently there is considerable variation in
      the diagnosis and management of hymenoptera venom allergy in the United Kingdom.
      This audit has demonstrated that the current international guidelines for the
      diagnosis and management of hymenoptera venom allergy are not being followed by
      UK allergy practitioners.

PMID- 18727622
TI  - Expression of inflammatory mediators in the otitis media induced by Helicobacter
      pylori antigen in mice.
AB  - Helicobacter pylori is a Gram-negative bacterium that is recognized as one of the
      key factors in gastric diseases such as gastritis, peptic ulcer and gastric
      cancer. Recent studies have shown relationships between H. pylori and extra
      digestive diseases, and the presence of H. pylori in the middle ear and upper
      respiratory tract has been reported. However, the role of H. pylori in middle ear
      disease remains unclear. The present study demonstrated that H. pylori whole-cell
      protein directly induces macrophage migration inhibitory factor, macrophage
      inflammatory protein 2, interleukin 1 beta and tumor necrosis factor alpha in
      middle ear epithelium in mice, and severe proliferation of inflammatory cells was
      observed in middle ear cavity inoculated with H. pylori whole-cell protein. In
      addition, trans-tympanic injection of macrophage migration inhibitory factor up
      regulated expression of macrophage inflammatory protein 2 in the middle ear.
      These findings indicate that H. pylori infection causes immunological
      inflammation in middle ear epithelium, and H. pylori may play a significant role
      in otitis media.

PMID- 18727623
TI  - Hypothetical review: thymic aberrations and type-I interferons; attempts to
      deduce autoimmunizing mechanisms from unexpected clues in monogenic and
      paraneoplastic syndromes.
AB  - In sporadic autoimmune disorders, dendritic cells are increasingly being
      incriminated as agents provocateurs. However, the mechanisms and any 'danger
      signals' that induce them to autoimmunize remain enigmatic. Here, we focus on
      unexpected clues from two prototypic/ highly informative autoimmune syndromes,
      acquired thymoma-associated myasthenia gravis and the monogenic autoimmune
      polyendocrine syndrome type-1 (APS1), caused by mutations in the AutoImmune
      Regulator (AIRE). Both involve the thymus, and in both we find early, persistent,
      highly prevalent and high-titre neutralizing autoantibodies against type-I
      interferons, regardless of the exact AIRE genotype or the characteristically
      variable clinical phenotype in APS1. Thus these key innate<-->adaptive immune
      intermediaries are now implicated in APS1 and paraneoplastic myasthenia as well
      as in systemic lupus erythematosus and other sporadic autoimmune disorders. The
      currently accepted notion that autoimmunization proceeds automatically (by
      'default') does not explain how, when or where autoimmune responses are initiated
      against which targets in APS1, or whether exogenous or internal danger signals
      are involved, or predict whether the primary auto-immunogenic targets are AIRE
      dependent. As the parallels between these syndromes must hold novel clues to
      these puzzles, they demand explanations. To unify these and other findings, we
      propose that autoimmunization occurs centrally in aberrant thymic environments
      rendered 'dangerous' by AIRE-deficiency (possibly by excess undegraded nucleic
      acids/dead cell debris). The ensuing autoreactivity focuses early on the locally
      abundant type I interferons and then on other peripheral tissue autoantigens that
      are still expressed despite the absence of AIRE. These ideas raise numerous
      questions that others may already have the materials to address.

PMID- 18727624
TI  - Prognostic value of phagocytic activity of neutrophils and monocytes in sepsis.
      Correlation to CD64 and CD14 antigen expression.
AB  - The role of the phagocytic function of monocytes and neutrophils in sepsis has
      been poorly investigated. The present study evaluated the impact of the
      phagocytic activity of neutrophils and monocytes on the outcome of patients with
      severe sepsis. Thirty-one patients and 30 healthy individuals were enrolled in
      the study. The phagocytic activity of monocytes and neutrophils was evaluated
      during 24 h after admission and the results were correlated to the expression of
      CD64 on neutrophils and monocytes, CD14 antigen on monocytes, the Simplified
      Acute Physiology Score II and the patients' survival. A reduced phagocytic
      activity of neutrophils during the first 24 h after admission was a negative
      predictor for survival. Increased expression of CD64 antigen on polymorphonuclear
      cells (PMNs) and monocytes was favourably correlated to the patients' survival.
      In multivariate analysis the phagocytic activity of PMNs was the only independent
      predictor factor for survival. Patients with PMN phagocytic activity <37% had
      lower expression of CD64 on monocytes and PMNs and worse outcome, while those
      with phagocytic activity >37% had higher expression of CD64 on monocytes and PMNs
      and better outcome. Reduced phagocytic activity of neutrophils may represent a
      state of neutrophil inactivation similar to that previously described for
      monocytes during the compensatory anti-inflammatory response.

PMID- 18727625
TI  - Potential therapy of Fc-antigen combination-encoding DNA vaccination in mouse
      allergic airway inflammation.
AB  - Vaccination with allergen-encoding DNA has been proposed as having potential for
      allergen-specific immunotherapy. In this study, we examine the therapeutic effect
      of allergen-encoding DNA vaccination directly to dendritic cells (DCs) on
      allergen-induced allergic airway inflammation in a mouse model and explore
      potential mechanism. Ovalbumin (OVA)-sensitized and challenged mice were
      immunized with DNA vaccine and received bronchoalveolar lavage (BAL) 1 day after
      the last challenge, to measure BAL levels of interleukin (IL)-4, IL-5, interferon
      (IFN)-gamma and differential cell count. Pulmonary DCs and Spleen DCs were
      purified and sorted according to the expression of CD(11c) (+)CD(80) (+) and
      CD(11c) (+)CD(86) (+) co-stimulatory molecules. Our data demonstrated that DNA
      vaccine therapy with OVA-Fc-pcDNA(3.1) significantly prevented OVA-increased
      levels of IL-4, IL-5 and the percentage of eosinophils and OVA-decreased level of
      IFN-gamma. OVA-Fc-pcDNA(3.1)-treated mice had less severity of airway
      inflammation, and lower expression of CD(11c) (+)CD(80) (+) and CD(11c) (+)CD(86)
      (+) on pulmonary DCs, as compared with animals with OVA-pcDNA(3.1,) pcDNA(3.1)
      and OVA respectively. DNA vaccine encoding both Fc and OVA was shown to be more
      effective than DNA vaccine encoding OVA alone. Our data indicate that Fc-antigen
      combination-encoding DNA vaccination has better preventive effects on antigen
      induced airway inflammation by regulating DCs, and may be a new alternative
      therapy for asthma.

PMID- 18727626
TI  - Lessons learnt from many years of experience using anti-D in humans for
      prevention of RhD immunization and haemolytic disease of the fetus and newborn.
AB  - For 40 years prophylactic anti-D has been given to D-negative women after
      parturition to prevent haemolytic disease of the fetus and newborn. Monoclonal or
      recombinant anti-D may provide alternatives to the current plasma-derived
      polyclonal IgG anti-D, although none of them have yet proved as effective in
      phase 1 clinical trials. The variation in efficacy of the antibodies may have
      been influenced by heterogeneity in glycosylation of anti-D produced from
      different cell lines. Some aspects of the conduct of the human studies, most
      notably the use of low doses of anti-D and target D positive red cells in vivo,
      may aid the design of the clinical development of other immunomodulatory drugs in
      order to minimize adverse effects.

PMID- 18727627
TI  - Human spleen contains different subsets of dendritic cells and regulatory T
      lymphocytes.
AB  - Most knowledge about dendritic cells (DCs) and regulatory T cells in humans has
      been gathered from circulating cells but little is known about their frequency
      and distribution in lymphoid organs. This report shows the frequency, phenotype
      and location of DCs and regulatory T cells in deceased organ donors' spleens. As
      determined by flow cytometry, conventional/myeloid DCs (cDCs) CD11c(high)HLA
      DR(+)CD123(-/low) were 2.3 +/- 0.9% and LIN(-) HLA-DR(+)CD11c(high) 2.1 +/- 0.3%
      of total spleen cells. Mature CD11c(high)HLA-DR(+)CD83(+) were 1.5 +/- 0.8% and
      1.0 +/- 1.6% immature CD11c(high)HLA-DR(+)CD83(-) cDC. There were 0.3 +/- 0.3%
      plasmacytoid DCs (pDC) CD11c(-/low)HLA-DR(+)CD123(high) and 0.3 +/- 0.1% LIN(
      )HLA-DR(+)CD123(high). Cells expressing cDCs markers, BDCA-1 and BDCA-3, and pDCs
      markers BDCA-2 and BDCA-4 were observed in higher frequencies than DCs with other
      phenotypes evaluated. CD11c(+), CD123(+) and CD83(+) cells were located in
      subcapsular zone, T cells areas and B-cell follicles. CD4(+)CD25(high) Tregs were
      0.2 +/- 0.2% and CD8(+)CD28(-) comprised 11.5 +/- 8.1% of spleen lymphocytes.
      FOXP3(+) cells were found in T- and B-cell areas. The improvement in cell
      separation, manipulation and expansion techniques, will facilitate the
      manipulation of donor spleen cells as a part of protocols for induction and
      maintenance of allograft tolerance or treatment of autoimmune diseases.

PMID- 18727628
TI  - Expansion of a unique macrophage subset in rheumatoid arthritis synovial lining
      layer.
AB  - The Z39Ig protein (complement receptor for C3b and iC3b) is expressed on resident
      tissue macrophages in various tissues. This study was undertaken to examine the
      distribution of Z39Ig+cells and their phenotypic features in rheumatoid arthritis
      (RA) synovium, in comparison with those of osteoarthritis (OA) and psoriatic
      arthritis (PsA) synovium. Monoclonal anti-Z39Ig antibody was produced by
      immunizing Z39Ig transfected murine pre B cells and used for the identification
      of Z39Ig+cells. Z39Ig+cells were further stained with antibodies to macrophages,
      fibroblast-like synoviocytes, complement receptors and dendritic cells by using
      the double immunostaining method in normal, RA, OA and PsA synovium. RA synovial
      mononuclear cells were double-stained using anti-Z39Ig and anti-CD11c antibodies
      and sorted into Z39Ig+CD11c+cells and Z39Ig+CD11c-cells. These cell populations
      were then analysed by electron microscopy. The expression of the Z39Ig protein
      was limited to intimal macrophages in normal, RA, OA and PsA synovium. The
      numbers of Z39Ig+CD11c+cells and the ratios of Z39Ig+CD11c+cells to Z39Ig+cells
      were increased in the synovial lining layer of RA as compared with those of OA
      and PsA. The ultrastructural analysis of Z39Ig+CD11c+cells showed the character
      of macrophages with many secondary lysosomes and swelling of mitochondria. Z39Ig+
      cells appeared to be useful for identification of resident tissue macrophages in
      normal synovium and the corresponding macrophages in the synovial lining layer of
      inflammatory arthritis. Expansion of Z39Ig+CD11c+cells was characteristic of RA
      synovial lining layer.

PMID- 18727629
TI  - Antibodies to amino acid 200-239 (p200) of Ro52 as serological markers for the
      risk of developing congenital heart block.
AB  - Maternal autoantibodies to the p200-epitope of Ro52 have been suggested to
      correlate with development of congenital heart block. The aim of the present
      study was to evaluate the clinical relevance and predictive value of p200
      antibodies in high-risk pregnancies. Sera from 515 Finnish, Swedish and American
      women were included in the study. Sera originated from 202 mothers with an infant
      affected by second- or third-degree atrioventricular block (AVB), 177 mothers
      with rheumatic disease having infants with normal heart rate and female blood
      donors (n = 136). A novel serological assay for Ro52 p200-antibodies with intra-
      and inter-assay variability of 3% and 3.8% respectively was developed. Mothers of
      children affected by AVB II-III had significantly higher p200-antibody levels
      than mothers with rheumatic disease having children with normal heart rate (P <
      0.001). In the Swedish cohort, a distinction between foetuses with normal
      conduction, AVB I, AVB II and III was possible. A significant difference in anti
      p200 levels between AVB I and AVB II-III groups compared with foetuses with
      normal conduction (P < 0.05 and P < 0.01) was observed. Using p200-antibodies as
      a second step analysis in Ro52-positive pregnancies increased the positive
      predictive value for foetal cardiac involvement (AVB I, II or III) from 0.39
      (0.27-0.51) to 0.53 (0.37-0.68). In conclusion, Ro52 p200-antibodies may occur in
      women with unaffected children, but levels are significantly higher in mothers of
      children with congenital heart block and are suggested as a relevant marker in
      evaluating the risk for foetal AV block.

PMID- 18727630
TI  - Human TSLP directly enhances expansion of CD8+ T cells.
AB  - Human thymic stromal lymphopoietin (TSLP) promotes CD4(+) T-cell proliferation
      both directly and indirectly through dendritic cell (DC) activation. Although
      human TSLP-activated DCs induce CD8(+) T-cell proliferation, it is not clear
      whether TSLP acts directly on CD8(+) T cells. In this study, we show that human
      CD8(+) T cells activated by T-cell receptor stimulation expressed TSLP receptor
      (TSLPR), and that TSLP directly enhanced proliferation of activated CD8(+) T
      cells. Although non-stimulated human CD8(+) T cells from peripheral blood did not
      express TSLPR, CD8(+) T cells activated by anti-CD3 plus anti-CD28 did express
      TSLPR. After T-cell receptor stimulation, TSLP directly enhanced the expansion of
      activated CD8(+) T cells. Interestingly, using monocyte-derived DCs pulsed with a
      cytomegalovirus (CMV)-specific pp65 peptide, we found that although interleukin-2
      allowed expansion of both CMV-specific and non-specific CD8(+) T cells, TSLP
      induced expansion of only CMV-specific CD8(+) T cells. These results suggest that
      human TSLP directly enhances expansion of CD8(+) T cells and that the direct and
      indirect action of TSLP on expansion of target antigen-specific CD8(+) T cells
      may be beneficial to adoptive cell transfer immunotherapy.

PMID- 18727632
TI  - CD8 chemokine receptors in chronic obstructive pulmonary disease.
AB  - Increased lung CD8 cells and their expression of chemokine receptors CXCR3 and
      CCR5 have been previously reported in chronic obstructive pulmonary disease
      (COPD). Alterations of CD8-CCR3 and -CCR4 expression and their ligands in COPD
      patients have not been fully investigated. The objective of this study was to
      assess in COPD patients: (i) broncho-alveolar lavage (BAL) CD8 CCR3 and CCR4
      expression in COPD patients; and (ii) airway levels of the CCR3 ligands, CCL11
      and CCL5. Multi-parameter flow cytometric analysis was used to assess BAL CD3 and
      CD8-chemokine receptor expression in COPD patients, smokers and healthy non
      smokers (HNS). CCL5 and CCL11 levels were measured in BAL, and from the
      supernatants of lung resection explant cultures. CD8-CCR3 and -CCR5 expression
      (means) were increased in COPD patients (22% and 46% respectively) and smokers
      (20% and 45%) compared with HNS (3% and 22%); P < 0.05 for all comparisons.
      CD3CXCR3 expression was raised in smokers and COPD while CD8CXCR3 and CD3 and CD8
      CCR4 expression was similar between groups. CD8CCR5 expression correlated to
      smoking pack years (r = 0.42, P = 0.01). COPD explants released more CCL5
      compared with smokers (P = 0.02), while there was low level CCL11 production.
      CD8CCR3 and CCR5 expression appear to be regulated by cigarette smoke exposure.
      We show that COPD lung tissue released more CCL5, suggesting a role for CCL5-CCR3
      signalling in pulmonary CD8 recruitment in COPD.

PMID- 18727631
TI  - Decreased 4-1BB expression on CD4+CD25 high regulatory T cells in peripheral
      blood of patients with multiple sclerosis.
AB  - As a tumour necrosis factor receptor superfamily member, 4-1BB (CD137) is
      preferentially expressed in CD4+CD25+ regulatory T cells (Tregs) and has been
      suggested to play an important role in regulating the generation or function of
      Tregs. Recent studies of human Tregs have shown that blood CD4+CD25(high) T cells
      were much closer to Tregs in terms of their functionality. Furthermore,
      CD4+CD25(high) Tregs have been found to have a decreased effector function in
      patients with multiple sclerosis (MS). In this study, we examined the expression
      of 4-1BB and soluble 4-1BB (s4-1BB) protein levels in the peripheral blood of MS
      patients. Compared with healthy controls, MS patients had decreased 4-1BB
      expression in their CD4+C25(high) Tregs and increased plasma s4-1BB protein
      levels. Moreover, the plasma s4-1BB levels of MS patients were shown to be
      inversely correlated with the 4-1BB surface expression of CD4+CD25(high) Tregs.
      The down-regulated 4-1BB expression on CD4+CD25(high) Tregs of MS patients may be
      involved in the impaired immunoactivity of these Tregs. The elevated s4-1BB
      levels may, at least in part, function as a self-regulatory attempt to inhibit
      antigen-driven proliferation of Tregs or their immunosuppressive activity.

PMID- 18727633
TI  - Transgenic tomato expressing interleukin-12 has a therapeutic effect in a murine
      model of progressive pulmonary tuberculosis.
AB  - Host control of mycobacterial infection, in both human and mouse models, has been
      shown to be associated with the production of interferon (IFN)-gamma by CD4(+) T
      cells. Interleukin (IL)-12 is known to be a crucial cytokine in the
      differentiation of IFN-gamma-producing T helper 1 (Th1) cells. To determine
      whether continuous administration of IL-12 expressed in transgenic tomato (TT-IL
      12) has therapeutic efficacy in a murine model of pulmonary tuberculosis, BALB/c
      mice were infected with either Mycobacterium tuberculosis H37Rv strain or a multi
      drug-resistant clinical isolate (MDR) and treated with a daily oral dose of TT
      IL12 crude fruit extracts. For the early H37Rv infection, TT-IL-12 administration
      was started 1 day before infection and continued for 60 days. In the H37Rv or MDR
      late infection, treatment was started 60 days after infection and continued for
      another 60 days. In both phases of infection, TT-IL-12 administration resulted in
      a reduction of bacterial loads and tissue damage compared with wild-type tomato
      (non-TT). The Th1 response was increased and the Th2 response was reduced. In the
      late infection, a long-term treatment with TT-IL-12 was necessary. We demonstrate
      that TT-IL-12 increases resistance to infection and reduces lung tissue damage
      during early and late drug-sensitive and drug-resistant mycobacterial infection.

PMID- 18727634
TI  - Headache disorders in developing countries: research over the past decade.
AB  - The majority of people with primary headache disorders live in the developing
      world. The contribution of low and middle income (LAMI) countries to headache
      research has not been previously characterized. A search was performed for
      clinical research publications between the years 1997 and 2006, using the search
      terms 'headache' OR 'headache disorders' AND 'primary' OR 'migraine' AND 'each of
      the LAMI countries' in 67 databases. Articles in English or with abstracts in
      English translation were included. These publications were scrutinized for study
      characteristics. Two hundred and twenty-seven publications from 32 LAMI countries
      were found. Half (50.2%) of these were from three middle-income countries
      (Brazil, Turkey and Iran), whereas 24 (10.6%) came from low-income countries.
      Most of the research focused on migraine. Only 29.5% of the articles involved
      treatment of headache. The understanding of headache disorders in LAMI countries
      is derived from a limited number of publications from relatively few countries.
      Identifying gaps in headache research in the developing world is strategic for
      targeting research policy.

PMID- 18727635
TI  - The visual aura rating scale as an outcome predictor for persistent visual aura
      without infarction.
AB  - Persistent visual aura without infarction is rare. Its pathogenic mechanism is
      unknown, and the response to migraine prophylactic agents varies. A systematic
      analysis of 29 patients (23 from the literature and six in the present report;
      6M/23F, mean age 37.6 years) was carried out in terms of demographics, headache
      and visual symptom profiles, treatment regimens and outcomes. Patterns of visual
      disturbances (VDs) were re-assessed with the Visual Aura Rating Scale (VARS,
      score 0-10). Even though the majority of patients had headache improvement, only
      eight (27.6%) had complete resolution of persistent VD, without definite
      relevance to any specific agent. Patients with complete resolution of VD tended
      to have scotoma (50.0% vs. 0%; P = 0.003), unilateral/homonymous involvement
      (62.5% vs. 9.5%; P = 0.008), higher VARS scores (1.88 +/- 1.73 vs. 0.10 +/- 0.30;
      P < 0.001) and shorter duration of illness (10.0 +/- 12.9 vs. 60.2 +/- 90.9
      months, P = 0.008) compared with those without. These findings remained even when
      the six current patients were not included for analyses. In conclusion, the
      prognosis of persistent VD was poor, and higher VARS scores, i.e. more typical of
      migraine visual aura, predicted a better outcome. For those with a potential for
      complete resolution, improvement would occur early in the course.

PMID- 18727636
TI  - Interictal brain 5-HT1A receptors binding in migraine without aura: a 18F-MPPF
      PET study.
AB  - In this study we aimed to assess the brain distribution of 5-HT(1A) receptors in
      migraine patients without aura. Ten female migraine patients and 24 female
      healthy volunteers underwent magnetic resonance imaging and positron emission
      tomography using a radioligand antagonist of 5-HT(1A) receptors [4-(2'
      methoxyphenyl)-1-[2'-(N-2-pirydynyl)-p-fluorobenzamido]-ethylpiperazine ((18)F
      MPPF)]. A simplified reference tissue model was used to generate parametric
      images of 5-HT(1A) receptor binding potential (BP) values. Statistical
      Parametrical Mapping (SPM) analysis showed increased MPPF BP in posterior
      cortical areas and hippocampi bilaterally in patients compared with controls.
      Region of interest (ROI) analysis showed a non-significant trend in favour of a
      BP increase patients in cortical regions identified by the SPM analysis except in
      hippocampi, left parietal areas and raphe nuclei. During the interictal period of
      migraine patients without aura, the increase of MPPF BP in posterior cortical and
      limbic areas could reflect an increase in receptor density or a decrease of
      endogenous serotonin, which could explain their altered cortical excitability.

PMID- 18727637
TI  - Lack of seasonal variation in menstrually-related migraine.
AB  - The aim of the study was to study seasonal variation in migraine headache in a
      group of women with menstrually-related migraine (MRM) compared with non
      menstrual migraine. Via newspaper advertisement, women with migraine living in
      North Norway were invited. The patients were included by questionnaire and
      telephone interview. We prospectively recorded migraine attacks from a 12-month
      headache diary performed by a group of 62 women with a mean age of 36.0 years
      (range 16-46 years), who fulfilled the criteria of migraine without aura. Of
      these, 29 had MRM and 33 non-menstrual migraine. Mean ratio between number of
      attacks in the light arctic season (May-June-July) divided with total number of
      migraine attacks during 12 months was 0.24 (9.4/38.4) in the group of MRM
      compared with 0.25 (5.6/22.1) in others (confidence interval -4.2, 6.3, P =
      0.84). Nor were there more migraine attacks in the dark season in an arctic area
      (November-December-January) in any group. We found a higher migraine attack rate
      in those with MRM, but no indication of more or less frequency of attacks during
      the bright arctic season. These findings support the assumption that MRM and
      seasonal variation of migraine are due to different mechanisms.

PMID- 18727638
TI  - The blood-brain barrier in migraine treatment.
AB  - Salient aspects of the anatomy and function of the blood-barrier barrier (BBB)
      are reviewed in relation to migraine pathophysiology and treatment. The main
      function of the BBB is to limit the access of circulating substances to the
      neuropile. Smaller lipophilic substances have some access to the central nervous
      system by diffusion, whereas other substances can cross the BBB by carrier
      mediated influx transport, receptor-mediated transcytosis and absorptive-mediated
      transcytosis. Studies of drugs relevant to migraine pathophysiology and treatment
      have been examined with the pressurized arteriography method. The drugs, given
      both luminally and abluminally, provide important notions regarding antimigraine
      site of action, probably abluminal to the BBB. The problems with the BBB in
      animal models designed to study the pathophysiology, acute treatment models and
      preventive treatments are discussed with special emphasize on the triptans and
      calcitonin gene-related peptide (CGRP). The human experimental headache model,
      especially the use of glycerol trinitrate (the nitric oxide model), and
      experiences with CGRP administrations utilize the systemic administration of the
      agonists with effects on other vascular beds also. We discuss how this can be
      related to genuine migraine attacks. Our view is that there exists no clear proof
      of breakdown or leakage of the BBB during migraine attacks, and that antimigraine
      drugs need to pass the BBB for efficacy.

PMID- 18727639
TI  - Efficacy of gabapentin in the treatment of SUNCT syndrome.
AB  - This study was designed to evaluate the efficacy of gabapentin (GBP) in the
      treatment of SUNCT syndrome on a relatively large sample of Persian patients.
      Eight patients with SUNCT syndrome underwent a 4-week, open-label, daily
      treatment of 600-900 mg GBP. The frequency, intensity and duration of attacks
      were compared before and after the trial. After 4 weeks of treatment, intensity,
      duration and frequency of headaches were significantly (P < 0.05) reduced. In
      addition, five patients (62.5%) were completely relieved from headaches, and in
      the other three patients the mean intensity, frequency and duration of headaches
      were decreased notably. In this study, GBP was well tolerated and no unfavourable
      side-effects were reported. After the end of the trial all patients continued the
      medication, and after 3 months none reported undesired side-effects or return of
      the headaches to the pre-treatment status. Our patients had a significant
      response to GBP, and considering other case reports on the effectiveness of GBP
      in the treatment of SUNCT syndrome, we propose that, taking into account the good
      side-effect profile and lack of interactions of GBP, this drug could be
      considered as an option for the treatment of SUNCT.

PMID- 18727640
TI  - Olfactory hypersensitivity in migraineurs: a H(2)(15)O-PET study.
AB  - Olfactory hypersensitivity (OHS) may occur during migraine attacks and seems to
      be very specific to this form of headache. OHS is also observed during migraine
      free periods and is associated with the presence of odour-triggered attacks. Yet
      the pathophysiology of OHS remains unknown. The aim of our study was to evaluate
      olfactory processing in migraineurs with OHS and to investigate whether regional
      cerebral blood flow (rCBF) associated with olfactory stimulation is modified in
      these patients compared with controls. Eleven migraineurs with OHS and 12
      controls participated in a H(2)(15)O-positron emission tomography study,
      including three scans in which odours were delivered and three scans where only
      odourless air was delivered. rCBF during olfactory condition was compared with
      that for the odourless baseline condition. Between-group analyses were performed
      using voxel-based and region-of-interest analyses. During both olfactory and non
      olfactory conditions, we observed higher rCBF in the left piriform cortex and
      antero-superior temporal gyrus in migraineurs compared with controls. During
      odour stimulation, migraineurs also showed significantly higher activation than
      controls in the left temporal pole and significantly lower activation in the
      frontal (left inferior as well as left and right middle frontal gyri) and temporo
      parietal (left and right angular, and right posterior superior temporal gyri)
      regions, posterior cingulate gyrus and right locus coeruleus. These results could
      reflect a particular role of both the piriform cortex and antero-superior
      temporal gyrus in OHS and odour-triggered migraine. Whether these rCBF changes
      are the cause or a consequence of odour-triggered migraines and interictal OHS
      remains unknown. Further comparisons between migraineurs with and without OHS are
      warranted to address this issue. The abnormal cerebral activation patterns during
      olfactory stimulation might reflect altered cerebrovascular response to olfactory
      stimulation due to the migraine disease, or an abnormal top-down regulation
      process related to OHS.

PMID- 18727641
TI  - Body mass index and headaches: findings from a national sample of US adults.
AB  - The objective was to study the cross-sectional association between body mass
      index (BMI) and the prevalence of severe headaches or migraines in a national
      sample of US adults. We used data from 7601 men and women aged > or = 20 years
      who participated in the National Health and Nutrition Examination Survey 1999
      2002. The age-adjusted prevalence of severe headaches or migraines during the
      previous 3 months was 34.0, 18.9, 20.7 and 25.9% among participants with a BMI <
      18.5, 18.5 to < 25, 25 to < 30 and > or = 30 kg/m(2), respectively. After
      adjusting for a variety of covariates in a logistic regression model, those with
      a BMI < 18.5 kg/m(2)[odds ratio (OR) 2.01; 95% confidence interval (CI) 1.34,
      3.02] or > or = 30 kg/m(2 )(OR 1.37; 95% CI 1.09, 1.72) had a significantly
      elevated OR for having a headache compared with participants with a BMI of 18.5-<
      25 kg/m(2). BMI is associated with the prevalence of severe headaches or
      migraines in a non-linear manner.

PMID- 18727642
TI  - Chronic daily headache in Brazil: a nationwide population-based study.
AB  - The objectives of this study were to estimate the 1-year prevalence of chronic
      daily headache (CDH) and the degree of the association of CDH with some
      sociodemographic characteristics of the adult population of Brazil. This was a
      cross-sectional, population-based study. We conducted telephone interviews with
      3848 people, aged 18-79 years, randomly selected from the 27 States of Brazil.
      The degree of the association was calculated through prevalence ratios, adjusted
      with Poisson regression by gender, age and some sociodemographic factors. The
      estimated 1-year gender- and age-adjusted prevalence of CDH was 6.9%. CDH was 2.4
      times more prevalent in women, 1.72 times more in unemployed, 1.63 times more in
      subjects with high household income and two times greater in those who did not
      exercise. The overall prevalence of CDH in Brazil is high. CDH is significantly
      more prevalent in women, the unemployed, subjects with higher income, and in
      those who do not exercise.

PMID- 18727643
TI  - Symptoms of migraine in the paediatric population by age group.
AB  - The revised criteria of the International Headache Society (IHS) for paediatric
      headache do not differentiate among age groups. This study aims to determine if
      different symptoms of migraine are specific or typical of different age groups of
      children. The files of 160 children (79 boys, 81 girls, mean age 10.39 +/- 3.71
      years) with migraine treated at the paediatric headache clinic of a tertiary
      centre were reviewed. The diagnosis was based on the criteria of the IHS (ICHD
      II). The patients were divided by age into three groups according to educational
      status, < or =6 years (preschool, group 1), >6 to < or =12 years (elementary
      school, group 2) and >12 to < or =18 years (secondary school, group 3), and
      compared by symptoms and signs. Symptoms of migraine with and without aura were
      also compared. There was no significant difference among the groups in rates of
      unilateral headache, phonophobia, photophobia, awakening pain, nausea or
      worsening of pain during physical activity. The parameters found to be
      statistically significant were dizziness and duration of migraine, and aura which
      increased with time. Frequency of attacks increased with age. The single
      statistically significant parameter found to be more frequent in younger age was
      vomiting. The statistically significant parameters of nausea and duration of
      migraine were more frequent in migraine with aura compared with migraine without
      aura. In conclusion, most of the migraine symptoms included in the 2004
      recommendations of the IHS are not typical for specific paediatric age groups,
      probably because brain maturity is a continuous process. A familial history of
      migraine is a frequent finding among all age groups and should be considered in
      the paediatric criteria, especially in younger children in whom diagnosis is more
      difficult. Vomiting may help the diagnosis of migraine in young children with a
      familial history of migraine.

PMID- 18727644
TI  - Differential effects of corticosteroids on the expression of cyclooxygenase-2,
      tumour necrosis factor-alpha and matrix metalloproteinase-9 in an animal model of
      migraine.
AB  - Nitric oxide (NO) directly activates trigeminal afferents innervating the dura
      mater and up-regulates inflammatory mediators. We evaluated NO-mediated up
      regulation of cyclooxygenase-2 (COX-2), tumour necrosis factor-alpha (TNF-alpha)
      and matrix metalloproteinase-9 (MMP-9), and the effect of glucocorticoid
      administration in an experimental animal model of migraine. COX-2 and TNF-alpha
      expression and MMP-9 activity were increased after continuous intravenous
      infusion of glyceryl trinitrate (GTN), a NO donor. Immunofluorescence staining
      demonstrated strong expression of these inflammatory mediators in the meningeal
      blood vessels. Methylprednisolone (MP) down-regulated MMP-9, which was reversed
      by RU486, a glucocorticoid receptor antagonist. COX-2 and TNF-alpha expression
      was not affected by MP or RU486 administration. These results suggest
      proinflammatory mediators are involved in the NO-mediated cascade of migraine
      pathogenesis. Further understanding of the activation of these inflammatory
      mediators at the transcriptional level may have therapeutic implications for
      future migraine treatments.

PMID- 18727645
TI  - Headache and multiple sclerosis: a population-based case-control study in
      Catania, Sicily.
AB  - We carried out a population-based case-control study to evaluate the association
      between multiple sclerosis (MS) and headache. We had previously determined the
      incidence of MS during 1990-1999 in Catania, Sicily, identifying 155 incident MS
      patients; these subjects underwent a telephone interview using a standardized
      questionnaire for headache. Diagnosis and classification of headaches were made
      according to International Headache Society criteria (1988). A control group was
      selected from the general population through random digit dialling. One hundred
      and one (65.2%) MS patients, of the 155 identified, and 101 controls were
      screened for headaches. Fifty-eight (57.4%) MS patients and 38 (37.2%) controls
      fulfilled the diagnostic criteria of headache. A significant association between
      MS and headache was found with an adjusted odds ratio, estimated by logistic
      regression, of 2.18 (95% confidence interval 1.27, 3.93). Frequency of headaches
      in our MS population is higher than in the general population, supporting the
      hypothesis of a possible association between these two conditions.

PMID- 18727646
TI  - High cervical epidural neurostimulation for cluster headache: case report and
      review of the literature.

PMID- 18727647
TI  - The importance of placebo in headache research.
AB  - The best way to appreciate the efficacy of drug and behavioural therapy in the
      acute and prophylactic treatment of headache is to perform placebo-controlled
      randomized trials. In order to plan and conduct these studies in the most
      appropriate way, it is desirable to know which factors influence the placebo
      response. This paper reviews factors which influence the placebo response in
      clinical trials, such as expectation, blinding, route of application of drugs and
      age, gender and geographical distribution. Response rates of placebo in the
      treatment of acute headache episodes are higher than in headache prophylaxis.
      Invasive procedures such as injections have a higher placebo response compared
      with oral drugs. Variables known to influence the placebo response have to be
      taken into consideration to calculate properly the power of planned randomized
      trials.

PMID- 18727648
TI  - Medication overuse headache: predictors and rates of relapse in migraine patients
      with low medical needs. A 1-year prospective study.
AB  - The aim of this study was to evaluate the rates and predictors of relapse, after
      successful drug withdrawal, in migraine patients with medication overuse headache
      (MOH) and low medical needs. The study population, study design, inclusion
      criteria and short-term effectiveness of the medication withdrawal strategies
      have been described elsewhere (Rossi et al., Cephalalgia 2006; 26:1097).
      Relapsers were defined as those patients fulfilling, at follow-up, the new
      International Classification of Headache Disorders, 2nd edn, appendix criteria
      for MOH. Complete datasets were available for 83 patients. At 1 year's follow up,
      the relapse rate was 20.5%. Univariate analysis showed that patients who relapsed
      had a longer duration of migraine with more than eight headache days/month, a
      longer duration of drug overuse, had tried a greater number of preventive
      treatments in the past, had a lower reduction of headache frequency after
      withdrawal, and had previously consulted a greater number of specialists. Binary
      logistic regression analysis was performed, and three variables emerged as
      significant predictors of relapse: duration of migraine with more than eight
      headache days/month [odds ratio (OR) 1.57, P = 0.01], a higher frequency of
      migraine after drug withdrawal (OR 1.48, P = 0.04) and a greater number of
      previous preventive treatments (OR 1.54, P = 0.01). In patients with migraine
      plus MOH and low medical needs, relapse seems to depend on a greater severity of
      baseline migraine.

PMID- 18727649
TI  - One-year course of paediatric headache in children and adolescents aged 8-15
      years.
AB  - The aims of the present study were the assessment of headache (HA) prevalence in
      German children and adolescents in the second year of a 4-year longitudinal study
      and the analysis of headache status change from year 1 to year 2. The original
      sample consisted of 8800 households with a child aged 7-14 years. A total of 4159
      households responded in both year 1 and year 2, yielding 3984 valid parent
      questionnaires. Data regarding various aspects of the child's HA history and
      general health were gathered via mailed questionnaires from the parents. Of the
      households returning valid parent questionnaires at survey 2, 48.9% reported
      their child to have experienced headaches during the previous 6 months (53% at
      survey 1). Weekly HA was reported for 6.5% of the children, monthly or less
      frequent HA for 16.5% and 25.9%, respectively. With regard to headache diagnosis,
      55.0% of the children and adolescents with HA experienced tension-type HA (TTH)
      and 11.3% migraine with or without aura (M). For more than half of the children
      and adolescents with HA (57.0%) the frequency of head pain remained stable over
      the period of 1 year (i.e. same frequency category in years 1 and 2). Improved
      and worsened HA status regarding frequency of occurrence was found in 22.3% and
      20.7% of the subjects, respectively. Thus, there was no definite trend towards an
      increase of HA episodes over the course of 1 year regarding the individual child
      or adolescent. The most stable type of HA was TTH.

PMID- 18727650
TI  - Tolerability of acute migraine medications: influence of methods of assessment
      and relationship with headache attributes.
AB  - Tolerability is an important attribute of patient satisfaction with, and
      consequence adherence to, migraine acute treatment. Nevertheless, the
      determinants of tolerability are poorly explored. Accordingly, our objectives
      were: (i) in subjects receiving triptans, to contrast two methods of assessing
      adverse events (AEs); and (ii) to explore the relationship between migraine
      features and treatment attributes with tolerability. We surveyed 365 migraineurs
      who had been using the same triptan for at least 3 months. After prospectively
      treating an attack, headache characteristics and treatment response were assessed
      using headache calendars. Subjects also completed a standardized questionnaire,
      first asking about any AE and then prompting patients with a list of possible
      AEs. We contrasted both sets of answers and conducted logistic regression to
      assess if headache attributes or response to therapy influenced tolerability.
      Using the unprompted method, AEs occurred in 11.5-36.4% of patients, depending on
      the triptan used. Using the prompted method, they ranged from 26.9 to 64.3%.
      Chest and neck tightness were spontaneously reported by 3.5% of the sample, vs.
      7.4% when prompted (P < 0.05). Chest pain was not spontaneously reported and was
      elicited in nine patients (2.5%, P = 0.002). Feeling groggy occurred in 5.7 and
      17.5% (P < 0.001). AEs were not a function of headache severity, disability,
      efficacy of the drug, time to meaningful relief with the drug or recurrence of
      pain. The report of AEs varies dramatically with the methods of assessment.
      However, tolerability is not influenced by the severity of the attacks or by
      medication efficacy.

PMID- 18727652
TI  - Evaluation of a capillary blood collection system for screening for
      hemoglobinopathies in remote areas.
AB  - Accurate estimation of hemoglobin (Hbs) A, Hb A(2), Hb F and abnormal Hb is
      required for diagnosis of hemoglobinopathies and genetic counseling. High
      pressure liquid chromatography (HPLC) is the most suitable approach available.
      But for 70% of the rural Indian population, HPLC analysis facilities are not
      available and screening would require transportation of samples to laboratories
      in bigger cities. We thus evaluated the feasibility of using a kit designed for
      measuring Hb A(1c) using capillary blood for collection and preservation of
      samples over a period of 15 days at different temperatures for screening for
      hemoglobinopathies. Capillary blood (5 microl) of 90 individuals was collected in
      the capillary collection system and run on the Variant Hemoglobin Testing System
      on days 1, 3, 5, 8, 12 and 15 after incubation at 4, 22, 37, 42 and 50 degrees C.
      The stability of different Hbs varied at different temperatures. The stability
      was maintained for 12 to 15 days by most of the samples up to 37 degrees C. Hb E
      was stable for 3 days up to at 37 degrees C and Hb D and Hb Q for 3 days up to 42
      degrees C. This capillary blood collection system would have tremendous potential
      for sample collection and transportation under adverse climatic conditions for
      screening of hemoglobinopathies in remote areas in different countries.

PMID- 18727651
TI  - Antithrombin effect on coagulation and fibrinolytic profiles after living donor
      liver transplantation: a pilot study.
AB  - Early after liver transplantation, patients are in a hypercoagulable state
      because of an imbalance between coagulation and fibrinolysis because of the slow
      recovery of depleted anticoagulant proteins. Antithrombin (AT) is used in
      anticoagulant protocols to prevent thrombosis. The subjects of the present study
      were 17 men and eight women that underwent living donor liver transplantation.
      The initial 15 cases were administered AT concentrate (1500 U/day) on
      postoperative days (POD) 1 through 3 (AT group) and the following 10 consecutive
      cases were not administered AT (control). AT, thrombin-AT complex, plasmin-alpha2
      plasmin inhibitor complex, thrombomodulin, fibrin degradation product D-dimer
      (FDP-DD) level, prothrombin time international normalized ratio, activated
      partial thromboplastin time, and platelet counts were measured. In the AT group,
      AT activity was maintained at levels >80% for 5 days after transplantation. In
      the control group, AT activity did not return to normal during the first 2 weeks
      after the operation. FDP-DD levels were significantly higher in the control group
      than in the AT group (P < 0.05). Six patients in the control group and three
      patients in the AT group required transfusions with platelet concentrate (P <
      0.05). AT supplementation might reduce FDP-DD levels and prevent decreased
      platelet counts in the early stages after liver transplantation.

PMID- 18727653
TI  - Saliva concentrations of RANKL and osteoprotegerin in smoker versus non-smoker
      chronic periodontitis patients.
AB  - OBJECTIVES: To compare the salivary receptor activator of NF-kappaB ligand
      (RANKL) and osteoprotegerin (OPG) concentrations in smokers versus non-smokers
      with chronic periodontitis. MATERIAL AND METHODS: Whole saliva samples were
      obtained from 67 untreated chronic periodontitis patients, of whom 34 were
      smokers, and from 44 maintenance patients, of whom 22 were smokers. Full-mouth
      clinical periodontal measurements were recorded. Saliva cotinine, sRANKL and OPG
      concentrations were determined by ELISA. Statistical analysis was performed using
      the Mann-Whitney U test, Bonferroni's correction for multiple comparisons and
      Spearman's correlations. RESULTS: Untreated smokers exhibited significantly
      higher values of clinical periodontal recordings than untreated non-smokers (all
      p<0.05). Salivary cotinine level correlated with clinical attachment level
      (p=0.023). Smoker versus non-smoker maintenance groups showed no significant
      differences in clinical parameters. There were significant differences in sRANKL
      and OPG concentrations between untreated and maintenance groups (all p<0.01).
      Salivary OPG concentration was significantly lower (all p<0.01) and the
      sRANKL/OPG ratio was higher (all p<0.01) in smokers than in non-smokers. OPG
      concentration correlated positively with probing depth, clinical attachment level
      and bleeding on probing (all p<0.005) and negatively with pack-year, and cotinine
      level (p<0.05). CONCLUSION: Salivary RANKL and OPG concentrations are suggested
      to be affected by smoking as not only the untreated but also the treated smokers
      exhibited higher RANKL and lower OPG concentrations than non-smokers.

PMID- 18727654
TI  - Association of cortisol and dehydroepiandrosterone sulphate levels in serum with
      periodontal status in older Japanese adults.
AB  - BACKGROUND AND AIM: The associations between periodontitis and stress-related
      steroid hormone levels released by the hypothalamic-pituitary-adrenal axis are
      poorly understood. In this study, we examined the association between levels of
      the stress-related steroid hormones cortisol and dehydroepiandrosterone-sulphate
      (DHEAS) and periodontitis in elderly subjects. METHODS: A total of 467 subjects
      participated in this study. Serum cortisol and DHEAS levels were determined, and
      a medical questionnaire regarding medical conditions and lifestyle was
      administered. In addition, clinical examinations including probing depth (PD),
      bleeding on probing (BOP), and clinical attachment loss (CAL) were conducted.
      RESULTS: The subjects were divided into tertiles on the basis of periodontitis
      severity. When the analysis was stratified by smoking status, we found that
      cortisol levels were significantly higher in those with severe CAL among subjects
      who had never smoked. Furthermore, multiple regression analysis showed that a
      higher level of cortisol was significantly associated with greater numbers of
      sites with severe CAL only in those who had never smoked, while a somewhat weaker
      association was also observed regarding cortisol/DHEAS ratio. In contrast, the
      level of DHEAS in serum was not associated with periodontitis. CONCLUSION: There
      were significant associations between serum cortisol level, including
      cortisol/DHEAS ratio, and periodontitis severity in elderly subjects who had
      never smoked.

PMID- 18727655
TI  - Herpes viruses in periodontal compromised sites: comparison between HIV-positive
      and -negative patients.
AB  - AIM: The objective of this study was to compare the frequency of herpes simplex
      virus type 1 (HSV-1), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV)
      in subgingival plaque, saliva and peripheral blood of HIV-positive and-negative
      patients with periodontal disease. MATERIAL AND METHODS: Fifty HIV-positive
      subjects (23 with gingivitis, 27 with periodontitis) and 50 healthy HIV-negative
      patients with chronic periodontitis were included in the study. Parameters of
      probing depth (PD), clinical attachment level (CAL), gingival index and plaque
      index were recorded. The samples were processed for viral identification by the
      nested polymerase chain reaction technique. RESULTS: HCMV was the most prevalent
      virus in HIV-positive (82%) and-negative patients (84%), and the detection in the
      three samples was similar (p>0.05). HSV-1 was the least prevalent virus in both
      groups, being detected in similar frequencies in oral sites and in peripheral
      blood. EBV-1 was found more frequently in saliva and subgingival plaque of HIV
      positive patients than in HIV-negative patients (p< or =0.05). CONCLUSIONS: EBV-1
      was more frequently recovered in oral sites of HIV-positive patients than in HIV
      negative patients.

PMID- 18727656
TI  - Improvement of periodontal condition by probiotics with Lactobacillus salivarius
      WB21: a randomized, double-blind, placebo-controlled study.
AB  - AIM: This randomized clinical study was designed to evaluate the effect of
      probiotic intervention using lactobacilli on the periodontal condition of
      volunteers without severe periodontitis. MATERIAL AND METHODS: Freeze-dried
      Lactobacillus salivarius WB21 (WB21)-containing tablets or a placebo were given
      to volunteers in a double-blind randomized study. A total of 66 volunteers were
      finally enrolled and randomly assigned to receive tablets containing WB21 (6.7 x
      10(8) CFU) with xylitol or xylitol alone (placebo) three times a day for 8 weeks.
      Periodontal clinical parameters and whole saliva samples were obtained at
      baseline (BL), 4 weeks, and the end of the interventional period (8 weeks).
      Salivary lactoferrin (Lf) levels were measured by enzyme-linked immunosorbent
      assay. Lactobacilli in saliva and plaque samples was detected by semi
      quantitative RT-PCR using 16S rRNA primers. RESULTS: Periodontal clinical
      parameters were improved in both groups after an 8-week intervention. Current
      smokers in the test group showed a significantly greater improvement of plaque
      index and probing pocket depth from BL when compared with those in the placebo
      group. Salivary Lf level was also significantly decreased in the test group
      smokers. CONCLUSION: Our results indicate that probiotics could be useful in the
      improvement/maintenance of oral health in subjects at a high risk of periodontal
      disease.

PMID- 18727657
TI  - Clinical and microbiological benefits of systemic metronidazole and amoxicillin
      in the treatment of smokers with chronic periodontitis: a randomized placebo
      controlled study.
AB  - AIM: The aim of this study was to evaluate the clinical and microbiological
      effects of scaling and root planing (SRP) alone or combined with metronidazole
      (MTZ) or with MTZ and amoxicillin (AMX) in the treatment of smokers with chronic
      periodontitis. METHODS: A double-blind, placebo-controlled, randomized clinical
      trial was conducted in 43 subjects who received SRP alone (n=15) or combined with
      MTZ (400 mg 3 x per day, n=14) or with MTZ+AMX (500 mg 3 x per day, n=14) for 14
      days. Clinical and microbiological examinations were performed at baseline and 3
      months post-therapy. Subgingival samples were analysed by checkerboard DNA-DNA
      hybridization. RESULTS: Subjects receiving MTZ+AMX showed the greatest
      improvements in mean probing depth and clinical attachment level. Both antibiotic
      therapies led to additional clinical benefits over SRP alone in initially
      shallow, intermediate, and deep sites. The SRP+MTZ+AMX therapy led to the most
      beneficial changes in the subgingival microbial profile. These subjects showed
      significant reductions in the mean counts and proportions of periodontal
      pathogens such as Tannerella forsythia, Porphyromonas gingivalis and Treponema
      denticola, and the greatest increase in proportions of host-compatible species.
      CONCLUSION: Significant advantages are observed when systemic antibiotics are
      combined with SRP in the treatment of smokers with chronic periodontitis. The
      greatest benefits in clinical and microbiological parameters are achieved with
      the use of SRP+MTZ+AMX.

PMID- 18727658
TI  - Raised chondroitin sulphate WF6 epitope levels in gingival crevicular fluid in
      chronic periodontitis.
AB  - AIM: To determine the levels of chondroitin sulphate (CS) WF6 epitope, recognized
      by WF6 monoclonal antibody, in gingival crevicular fluid (GCF) from different
      stages of periodontal disease and healthy periodontium, and to correlate those
      levels with clinical parameters. MATERIAL AND METHODS: GCF samples, collected
      from 389 sites, were analysed for the WF6 epitope levels by the competitive
      enzyme-linked immunosorbent assay. RESULTS: The median WF6 epitope level was
      significantly higher in chronic periodontitis sites (n=185) than in healthy and
      gingivitis sites (n=204) (p<0.001), whereas the median levels did not
      significantly differ between healthy (n=65) and gingivitis sites (n=139). The
      median level in severe periodontitis sites (n=60) was significantly higher than
      that in moderate periodontitis sites (n=63) (p=0.019). Similarly, the median
      level in moderate periodontitis sites was significantly higher than that in
      slight periodontitis sites (n=62) (p=0.001). The WF6 epitope levels significantly
      correlated with probing depth (r=0.777, p=0.001) and loss of clinical attachment
      level (r=0.814, p=0.001). CONCLUSION: Elevated CS WF6 epitope levels in GCF are
      associated with severity of periodontitis. The WF6 antibody may therefore be
      clinically applied to monitor disease severity and progression.

PMID- 18727659
TI  - Alveolar ridge augmentation using implants coated with recombinant human bone
      morphogenetic protein-7 (rhBMP-7/rhOP-1): radiographic observations.
AB  - AIM: The objective of this study was to radiographically evaluate the potential
      of a purpose-designed titanium porous-oxide implant surface coated with
      recombinant human bone morphogenetic protein-7 (rhBMP-7), also known as
      recombinant human osteogenic protein-1 (rhOP-1), to stimulate alveolar ridge
      augmentation. MATERIAL AND METHODS: Six young-adult Hound Labrador mongrel dogs
      were used. Three 10 mm titanium oral implants per jaw quadrant were placed 5 mm
      into the alveolar ridge in the posterior mandible following surgical extraction
      of the pre-molar teeth and reduction of the alveolar ridge leaving 5 mm of the
      implants in a supra-alveolar position. The implants had been coated with rhBMP-7
      at 1.5 or 3.0 mg/ml and were randomized to contralateral jaw quadrants using a
      split-mouth design. The mucoperiosteal flaps were advanced, adapted, and sutured
      to submerge the implants. Radiographic registrations were made immediately post
      surgery (baseline), and at weeks 4 and 8 (end of study). RESULTS: rhBMP-7-coated
      implants exhibited robust radiographic bone formation. At 8 weeks, bone formation
      averaged 4.4 and 4.2 mm for implants coated with rhBMP-7 at 1.5 and 3.0 mg/ml,
      respectively. There were no significant differences between the rhBMP-7
      concentrations at any observation interval. A majority of the implant sites
      showed voids within the newly formed bone at week 4 that generally resolved by
      week 8. The newly formed bone assumed characteristics of the resident bone.
      CONCLUSIONS: The titanium porous-oxide implant surface serves as an effective
      carrier for rhBMP-7 showing a clinically significant potential to stimulate local
      bone formation.

PMID- 18727660
TI  - Prospective trial of mycophenolate mofetil-cyclosporine A prophylaxis for acute
      GVHD after G-CSF stimulated allogeneic bone marrow transplantation with HLA
      identical sibling donors in patients with severe aplastic anemia and
      hematological malignancies.
AB  - The combination of methotrexate and cyclosporine A (MTX-CSA) is the standard
      regimen for the prevention of graft vs. host disease (GVHD) after allogeneic
      hematopoietic stem cell transplantation (allo-SCT) from HLA-identical siblings.
      Mycophenolate mofetil and CSA (MMF-CSA) combination has been successfully used
      for GVHD prophylaxis after non-reduced intensity conditioning (non-RIC) allo-SCT
      with peripheral blood or non-G-CSF stimulated bone marrow as stem cell source. We
      report the results of the first prospective trial of the MMF-CSA combination for
      acute GVHD prophylaxis in 47 patients after non-RIC G-CSF stimulated allo-BMT (G
      BMT) from HLA-identical siblings in patients with severe aplastic anemia (SAA) or
      hematological malignancies. Median age was 28 yr (range, 6-48 yr). Median follow
      up was 22 months. The median time to neutrophil and platelets recovery were nine
      d (range, 8-17) and 16 d (range, 10-28), respectively. Acute GVHD of grade II-IV
      and chronic GVHD occurred in 51% and 27%, respectively. Overall survival rates at
      two yr for patients with SAA and hematological malignancies were 87% and 65%,
      respectively. The event-free survival at two yr for patients with hematological
      malignancies was 76%. We concluded that MMF-CSA appears equivalent to MTX-CSA for
      GVHD prophylaxis in patients receiving non-RIC G-BMT from HLA-identical siblings,
      with a tendency for more rapid neutrophil engraftment.

PMID- 18727661
TI  - Steroid withdrawal five days after renal transplantation allows for the
      prevention of wound-healing complications associated with sirolimus therapy.
AB  - BACKGROUND: Sirolimus (SRL) can increase the risk of wound complications. In this
      study, we investigated the impact of steroids when added to SRL, in this side
      effect. METHODS: One hundred and forty-eight patients entered prospective studies
      comparing early (fifth day) with late (sixth month) steroid withdrawal. All
      patients were on SRL, added either to Tacrolimus (n = 56) or to cyclosporine (n =
      97). At 15th day after transplantation, 68 patients were on steroids (On-St
      group) and 80 were not (Off-St group). Wound complications considered were as
      follows: dehiscence, lymphocele, wound leakage, hematoma and seromas. Risk
      factors under analysis were as follows: body mass index, diabetes, rejection,
      creatininemia, length of dialysis before transplantation, recipient age, being on
      steroids at 15th day, SRL levels. RESULTS: The overall incidence of wound
      complications was significantly lower in Off-St group than in On-St group: 18.8%
      vs. 45.6%, respectively (p < 0.0004). In detail, lymphocele: 5.0% vs. 32.3% (p <
      0.0001); dehiscence 0% vs. 10.3% (p < 0.009), leakage 6.2% vs. 8.8% (p = NS),
      seromas 1.4% vs. 7.5% (NS). At multivariate analysis, the addition of steroids to
      SRL increases 4.2-fold the risk for wound complications. CONCLUSIONS: Early
      steroid withdrawal is effective in preventing both the incidence and the severity
      of wound-healing complications because of SRL regime, even when started with a
      loading dose.

PMID- 18727662
TI  - Hepatocellular carcinoma metastatic to skin: diagnostic utility of antihuman
      hepatocyte antibody in combination with albumin in situ hybridization.
AB  - BACKGROUND: Cutaneous metastases from hepatic neoplasms are rare. Histologic
      features of hepatocellular carcinoma (HCC) are often poorly differentiated,
      hindering accurate diagnosis on routine examination by hematoxylin-eosin stain.
      Antihuman hepatocyte antibody is highly sensitive for HCC but can be strongly
      expressed in other adenocarcinomas. Albumin in situ hybridization (ISH) is highly
      specific and sensitive for HCC; in combination with antihuman hepatocyte
      antibody, it has a diagnostic sensitivity approaching 100%. To our knowledge, the
      combination of antihuman hepatocyte antibody and albumin ISH has not previously
      been examined in the context of cutaneous HCC. METHODS: We present histologic
      findings and results of ancillary studies for three patients with metastatic HCC.
      These patients had a poorly differentiated cytokeratin-positive cutaneous
      neoplasm. All three cases were evaluated with antihuman hepatocyte antibody and
      albumin ISH. RESULTS: Neoplastic cells were strongly positive for antihuman
      hepatocyte antibody, and ISH detected albumin messenger RNA in nearly 100% of the
      neoplastic cells in all three cases. CONCLUSIONS: The combination of antihuman
      hepatocyte antibody and albumin ISH is highly sensitive and specific for HCC
      metastatic to skin and is useful in the differential diagnosis of a poorly
      differentiated cytokeratin-positive neoplasm.

PMID- 18727663
TI  - Gene expression profiling of porokeratosis.
AB  - BACKGROUND: Porokeratosis (PK) represents a heterogeneous group of disorders of
      keratinization and has a wide variety of clinical manifestations. PK may exhibit
      similarities with psoriasis at both clinical and molecular levels. The genetic
      basis and pathogenesis for PK remain elusive. METHODS: We studied the
      transcriptional profiles of three pairwise lesional and uninvolved skin biopsies
      from patients with different subtypes of PK using the Illumina BeadArray
      platform. RESULTS: A total of 37 upregulated genes were identified in our study,
      including wound-induced keratins, S100 calcium-binding protein genes involved in
      epidermal differentiation, as well as genes involved in mediating intercellular
      communication and the immune response. To our knowledge, this is the first study
      that characterizes the immune profile of PK lesions. CONCLUSIONS: Here, we report
      that keratinocytes (KCs)-harboring lesions have activated and overexpressed wound
      induced keratin genes, which appear to be coregulated with other genes involved
      in mediating epidermal differentiation, intercellular communication and immunity.
      This study, from the perspective of gene profiling, supports that gene
      misregulation in PK mimics that of psoriasis. Our data indicate that the genes
      implicated in the T-cell-mediated immune response pathway and activation of KCs
      play a key role in the pathogenesis of PK.

PMID- 18727664
TI  - Cutaneous localized annular chromoblastomycosis.
AB  - Chromoblastomycosis (CBM) is a difficult-to-treat dermal mycosis characterized by
      the presence of round, pigmented, sclerotic bodies formed by black fungi found in
      polymorphic lesions. According to the morphology of a lesion, different clinical
      types of the disease have been described. We present three patients who each
      developed a single, 10-cm diameter, 8 to 15-year-old, well-circumscribed, slow
      growing, annular, papulosquamous or papulosquamous-verrucous lesion, with no
      regression despite the use of topical antifungals. Skin scrapings and biopsies
      confirmed CBM and microculture defined the agent as Fonsecaea pedrosoi. The
      patients were treated with 200 mg/day of itraconazole for 6-9 months and were
      discharged after complete regression of the lesions. All were examined after the
      first and second year of the end of treatment and there were no signs of
      recurrence. A new clinical type of CBM is described, and itraconazole appears to
      be effective and safe in curing these patients after no more than 9 months of
      therapy.

PMID- 18727665
TI  - Dermal sheet preparations in the evaluation of dermal innervation in Parkinson's
      disease and multiple system atrophy.
AB  - BACKGROUND: Evaluation of dermal nerve fibers in conventional vertical sections
      is difficult because of the small number of fibers available for examination. In
      this study, we evaluated dermal sheet mounts for fibers in which the majority of
      fibers can be visualized. METHODS: We compared the dermal small fiber density in
      six Parkinson's disease (PD) and six multiple system atrophy (MSA) patients using
      dermal sheet preparations (DSP). DSP are based on epidermal-dermal separations
      and immunostaining of the entire dermis by the nerve growth factor receptor p75
      antibody that stains both autonomic and sensory fibers. RESULTS: The small fiber
      density was reduced in PD compared with MSA (p < 0.0001), suggesting the presence
      of small fiber neuropathy in PD. CONCLUSIONS: DSP offer a unique method of
      evaluation of dermal nerve fibers. This method can be used to evaluate small
      nerve fibers in many neurological disorders such as MSA and PD.

PMID- 18727666
TI  - Malignant peripheral nerve sheath tumor with numerous signet-ring and lipoblast
      like cells.

PMID- 18727668
TI  - Tumors composed of malignant epithelial and melanocytic populations: a case
      series and review of the literature.
AB  - Over the last 30 years, there have been approximately 49 case reports of tumors
      composed of both malignant epithelial and malignant melanocytic populations.
      Herein, we present four additional cases of combined tumors that consist of two
      phenotypically distinct but intermingled populations of malignant cells. Each
      tumor was composed of an invasive melanoma closely associated with either a basal
      cell carcinoma or a squamous cell carcinoma. We review all previous case reports
      in the English literature and attempt to clarify the terminology and summarize
      what is currently known about these unique tumors.

PMID- 18727667
TI  - Hydroxychloroquine-induced hyperpigmentation: the staining pattern.
AB  - We report two cases of hydroxychloroquine-induced hyperpigmentation presenting in
      a 50-year-old Caucasian female (case 1) and a 78-year-old female (case 2), both
      receiving 400 mg per day. Case 1 had an arthritis predominant undifferentiated
      connective tissue disease, which was treated with hydroxychloroquine for 4-5
      years. She presented with a mottled, reticulated macular gray pigmentation
      involving the upper back and shoulders. Case 2 had a history of systemic lupus
      erythematosus and rheumatoid arthritis, treated with hydroxychloroquine for 1.5
      years. She presented to the hospital for treatment of constrictive cardiomyopathy
      and was noted to have a blue macular pigmentation involving the right temple. The
      biopsies from both patients showed superficial dermal, yellow-brown, non
      refractile and coarsely granular pigment deposition. A Fontana-Masson stain
      highlighted some of these granules, while the Perl's iron stain was negative.
      Rare, previous reports of hyperpigmentation indicate the presence of both melanin
      and hemosiderin in patients being treated with antimalarial medication. To our
      knowledge, this staining pattern for hydroxychloroquine has not been previously
      reported in the literature and supports that hydroxychloroquine, in addition to
      chloroquine, binds to melanin.

PMID- 18727669
TI  - A comparative biochemical and structural analysis of the intracellular chorismate
      mutase (Rv0948c) from Mycobacterium tuberculosis H(37)R(v) and the secreted
      chorismate mutase (y2828) from Yersinia pestis.
AB  - The Rv0948c gene from Mycobacterium tuberculosis H(37)R(v) encodes a 90 amino
      acid protein as the natural gene product with chorismate mutase (CM) activity.
      The protein, 90-MtCM, exhibits Michaelis-Menten kinetics with a k(cat) of 5.5+/
      0.2s(-1) and a K(m) of 1500+/-100microm at 37 degrees C and pH7.5. The 2.0A X-ray
      structure shows that 90-MtCM is an all alpha-helical homodimer (Protein Data Bank
      ID: 2QBV) with the topology of Escherichia coli CM (EcCM), and that both
      protomers contribute to each catalytic site. Superimposition onto the structure
      of EcCM and the sequence alignment shows that the C-terminus helix3 is shortened.
      The absence of two residues in the active site of 90-MtCM corresponding to Ser84
      and Gln88 of EcCM appears to be one reason for the low k(cat). Hence, 90-MtCM
      belongs to a subfamily of alpha-helical AroQ CMs termed AroQ(delta.) The CM gene
      (y2828) from Yersinia pestis encodes a 186 amino acid protein with an N-terminal
      signal peptide that directs the protein to the periplasm. The mature protein,
      *YpCM, exhibits Michaelis-Menten kinetics with a k(cat) of 70+/-5s(-1) and K(m)
      of 500+/-50microm at 37 degrees C and pH7.5. The 2.1A X-ray structure shows that
      *YpCM is an all alpha-helical protein, and functions as a homodimer, and that
      each protomer has an independent catalytic unit (Protein Data Bank ID: 2GBB).
      *YpCM belongs to the AroQ(gamma) class of CMs, and is similar to the secreted CM
      (Rv1885c, *MtCM) from M.tuberculosis.

PMID- 18727670
TI  - Ecological and evolutionary consequences of niche construction for its agent.
AB  - Niche construction can generate ecological and evolutionary feedbacks that have
      been underinvestigated so far. We present an eco-evolutionary model that
      incorporates the process of niche construction to reveal its effects on the
      ecology and evolution of the niche-constructing agent. We consider a simple plant
      soil nutrient ecosystem in which plants have the ability to increase the input of
      inorganic nutrient as an example of positive niche construction. On an ecological
      time scale, the model shows that niche construction allows the persistence of
      plants under infertile soil conditions that would otherwise lead to their
      extinction. This expansion of plants' niche, however, requires a high enough rate
      of niche construction and a high enough initial plant biomass to fuel the
      positive ecological feedback between plants and their soil environment. On an
      evolutionary time scale, we consider that the rates of niche construction and
      nutrient uptake coevolve in plants while a trade-off constrains their values.
      Different evolutionary outcomes are possible depending on the shape of the trade
      off. We show that niche construction results in an evolutionary feedback between
      plants and their soil environment such that plants partially regulate soil
      nutrient content. The direct benefit accruing to plants, however, plays a crucial
      role in the evolutionary advantage of niche construction.

PMID- 18727671
TI  - Concordance and heritability of multiple sclerosis in Finland: study on a
      nationwide series of twins.
AB  - OBJECTIVES: To evaluate the changes in the multiple sclerosis (MS) concordance in
      twins, and the contribution of genetic and environmental factors to the aetiology
      of MS in Finland. BACKGROUND: Both genes and the environment contribute to the
      development of MS. A well-conducted twin study is an excellent means to assess
      the relative contribution of heritability and environmental factors. METHODS:
      Multiple sclerosis concordance was assessed for 10 Monozygotic and 14 dizygotic
      twin pairs using pairwise and probandwise concordance rates. The tetrachoric
      correlations in liability to disease for twin pairs were computed and a polygenic
      multifactorial model was used to estimate heritability. RESULTS: The pairwise
      concordance for MZ twins was 30% and for the DZ twins 14.3%, compared with 30%
      for MZ and 0% for DZ 20 years ago. The corresponding probandwise concordance
      rates were 46.2% and 25%. The genetic variance (heritability) was 15.3% (95% Cl
      0.0-77.6), the common environmental variance 73.7% (95% Cl 14.1-93.9) and the
      unique environmental variance 11.1% (95% Cl 2.3-30.0). CONCLUSIONS: As the
      concordance of MS in DZ twins has increased during the past two decades and the
      heritability estimate is low, it seems that the reported increase in MS incidence
      in Finland is mainly caused by environmental factors.

PMID- 18727672
TI  - Neutralizing antibodies against interferon beta: fluctuation is modest and titre
      dependent.
AB  - BACKGROUND AND PURPOSE: Neutralizing antibody (NAb) titres may vary over time and
      thereby some patients can either lose or regain therapeutic effect of interferon
      beta (IFNbeta). We assessed NAb titres in a large sample of multiple sclerosis
      (MS) patients to identify the pattern of fluctuation during 1-3 years. METHODS:
      Data from IFNbeta-treated MS patients who had been tested for NAbs twice (n =
      822) were analysed. NAb titres were compared between the first and the second
      samples across the critical NAb level of 150 TRU/ml, which we have previously
      reported to correlate with loss of bioactivity. RESULTS: Of patients with NAb
      titres high enough to indicate loss of bioactivity (>150 TRU/ml) in the first
      analysis 15% showed titres low enough to indicate a regained bioactivity.
      Conversely, 6% of those without detectable NAbs or NAb titres below the critical
      level of 150 TRU/ml had shifted to titres above this limit, indicating potential
      loss of bioactivity. Fluctuation did not differ between IFNbeta preparation used,
      treatment duration or sampling interval. CONCLUSION: A first NAb test is
      prognostic for the NAb status during the coming 1-3 years. Choice of IFNbeta
      preparation had no influence on the chance of reverting to lower levels once NAb
      titres are high.

PMID- 18727673
TI  - Brain atrophy as a marker of cognitive impairment in mildly disabling relapsing
      remitting multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: We have studied the relationship between
      neuropsychological impairment and magnetic resonance imaging (MRI) measures in
      mildly disabling relapsing-remitting multiple sclerosis (RRMS). METHODS: We
      compared measures of lesion burden and atrophy in 52 patients with Expanded
      Disability Status Scale <or= 3.0. Neuropsychological testing explored various
      cognitive domains: attention and processing speed (APS), verbal and visual memory
      (VerbM; VisM), visual/constructional processes (VC), executive functions and
      motor programming/coordination. Specific and global index scores were derived to
      classify patients as deteriorated or not deteriorated by comparing their
      performance with 51 matched normal control subjects. Brain MRI analysis included
      proton density (PD)-lesion volume and T1-hypointensity volume, measures of
      central atrophy, including the third ventricle width, and corpus callosum (CC).
      RESULTS: Patients with either APS, MCP or Verbal Learning impairments had a
      higher ventricular atrophy than unimpaired. The atrophy of the CC was only
      associated to VisM dysfunction. Patients with VisM deficits had higher lesion
      load on PD images. After controlling for age and education a higher third
      ventricle width was the best predictor for global and specific cognitive
      impairment. CONCLUSION: Our results suggest that cognitive impairment in RR
      patients with mild disease is better explained by atrophic changes than by total
      lesion load.

PMID- 18727674
TI  - Use of three-dimensional kinematic analysis following upper limb botulinum toxin
      A for children with hemiplegia.
AB  - BACKGROUND AND PURPOSE: To examine whether three-dimensional (3-D) kinematic
      analysis can detect changes in upper limb tasks (reach and hand-to-mouth) in
      children with hemiplegia, following upper limb botulinum toxin A injections.
      METHODS: Ten children with hemiplegic cerebral palsy (7 males, 3 females, aged 9
      17 years). Subjects received botulinum toxin A (Botox) injections into elbow
      forearm muscles combined with 6 weeks of occupational therapy. Participants
      completed a 3-D kinematic analysis of two upper limb tasks, Melbourne Assessment
      of Unilateral Upper Limb Function and modified Ashworth scores measured at
      baseline, 2, 6 and 12 weeks post-injection. RESULTS: Post-injections, elbow
      flexor muscle tone was reduced for 12 weeks (p < 0.05). Group differences in
      active range of motion during 3-D analysis tasks could not be demonstrated at any
      time post-intervention. However, individual analyses found that at 2 weeks post
      injection, three subjects had >15 degrees increases in active elbow extension and
      six subjects showed an increase of >25 degrees in forearm supination during
      performance of the reach and hand-to-mouth tasks, respectively. CONCLUSIONS: 3-D
      kinematics can detect changes in active movements during functional tasks
      following botulinum toxin A injections, suggesting this could be a potential
      objective outcome measure in a clinical trial.

PMID- 18727675
TI  - Treatment of corticosteroid refractory optic neuritis in multiple sclerosis
      patients with intravenous immunoglobulin.
AB  - BACKGROUND: Patients with severe visual loss because of optic neuritis refractory
      to high dose corticosteroids have limited therapeutic options. The use of
      intravenous immunoglobulin (IVIG) has been advocated in the past, but data are
      scarce. In this study, we use a protocol different from those used in other
      studies, with different timing and dosage. METHODS: Consecutive patients with
      corticosteroid-refractive optic neuropathy were treated with IVIG and compared
      with control patients who received only corticosteroids in an open-label, non
      randomized, controlled prospective study. RESULTS: Twenty-three patients received
      treatment with IVIG and 24 matched patients who did not receive treatment with
      IVIG were followed as controls. All patients had visual acuity 20/400 or worse in
      the affected eye. There was significant improvement in the IVIG group with 18/23
      (78%) subjects reaching near normal vision (20/30 or better), compared with the
      control group with only 3/24 (12.5%) responding similarly. CONCLUSIONS: The use
      of IVIG, following corticosteroids, may be useful using the protocol described
      herein, with sustained pulsed dosing. A larger controlled trial is indicated to
      confirm these results.

PMID- 18727676
TI  - A novel presenilin 2 mutation (V393M) in early-onset dementia with profound
      language impairment.
AB  - BACKGROUND: Mutations in the Presenilin 2 gene (PSEN2) are rare causes of
      Alzheimer's disease (AD). Pathogenic mutations in the genes associated with
      autosomal dominant inherited AD have been shown to alter processing of the
      amyloid precursor protein (APP) resulting in a relative increase of the amount of
      Abeta42 peptide. METHODS AND RESULTS: We present a patient with
      neuropathologically confirmed early-onset AD characterized by profound language
      impairment. The patient was heterozygous for a novel missense mutation in exon 11
      of the PSEN2 gene leading to a predicted amino acid substitution from valine to
      methionine in position 393, a conserved residue. However, in vitro expression of
      PSEN2 V393M cDNA did not result in detectable increase of the secreted Abeta42/40
      peptide ratio. The mutation was not found in 384 control individuals tested.
      CONCLUSIONS: The possible pathogenic nature of the mutation is not clarified. We
      discuss the limitations of functional PSEN2 studies and the challenges associated
      with genetic counselling of family members at risk.

PMID- 18727677
TI  - Ptosis, diplopia and statins: an association?

PMID- 18727678
TI  - Growth dependence on insulin-like growth factor-1 during the ketogenic diet.
AB  - PURPOSE: To examine the influence of the ketogenic diet (KD) on linear growth and
      insulin-like growth factor I (IGF-I) levels in children with pharmacotherapy
      resistant epilepsy. METHODS: A prospective study was designed to evaluate growth,
      serum IGF-I levels, blood beta-hydroxybutyric acid (beta-OHB), and seizure
      frequency before and during KD in 22 children (median age 5.5 years). Growth was
      assessed by measurements of weight, height, body mass index (BMI), and height
      velocity. Standard deviation scores (SDS) were calculated for all measured
      parameters as well as for serum IGF-I to eliminate the influence of age- and sex
      related differences among patients. RESULTS: Fourteen of the 22 patients
      responded to the KD. Weight, height, BMI, and height velocity decreased
      significantly during the KD. We found that the KD had profound influence on
      growth and IGF-I levels. No correlation was found between seizure response and
      growth alterations. Height velocity correlated negatively with beta-OHB during
      the KD. The slope of the regression of height velocity against IGF-I decreased
      significantly during the KD. CONCLUSIONS: Height velocity was most affected in
      those with pronounced ketosis, which implies that, in clinical practice, the
      level of ketosis should be related to outcomes in seizure response and growth.
      Our data indicate that growth disturbances and the decreased sensitivity of
      growth to similar IGF-I levels during KD are independent of seizure reduction.
      The metabolic status induced by KD may be the mechanism underlying both
      alterations of linear growth and seizure reduction.

PMID- 18727679
TI  - Automated MRI analysis for identification of hippocampal atrophy in temporal lobe
      epilepsy.
AB  - BACKGROUND: Hippocampal sclerosis is frequently associated with hippocampal
      atrophy (HA), which is often observed on routine magnetic resonance imaging (MRI)
      of patients with medial temporal lobe epilepsy (MTLE). Manual morphometry of the
      hippocampus is sensitive to detecting HA, but is time-consuming and prone to
      operator error. Automated MRI morphometry has the potential to provide rapid and
      accurate assistance in the clinical detection of HA. METHODS: We performed a
      voxel-based morphometry analysis of 23 consecutive subjects with MTLE and 58
      matched controls. Images from randomly selected 34 controls were used to create
      mean and standard deviation images of gray matter volume. Voxel-wise standardized
      Z-score hippocampal images from patients and the remaining 24 controls were cross
      checked with receiver operating characteristic (ROC) curves to evaluate
      sensitivity versus one-specificity rate for a binary classifier (atrophied versus
      normal hippocampi). RESULTS: The ipsilateral hippocampi of patients with MTLE
      displayed a significantly lower mean Z-score compared to the hippocampi of
      controls [F(2,67) = 33.014, p < 0.001, Tukey HSD < 0.001]. A classifier using the
      hippocampal gray matter Z-scores to discriminate between atrophied and normal
      hippocampi yielded a fitted ROC = 97.3, traditionally considered an excellent
      discriminator, with a standard error of classification of 1.173 individuals if
      100 patients and 100 controls are studied. CONCLUSION: Automatic morphometry can
      be potentially used as a clinical tool to assist the detection of HA in patients
      with MTLE. It can provide a quantifiable estimative of atrophy, which can aid in
      the decision about the presence of clinically relevant HA.

PMID- 18727680
TI  - Cellular mechanisms of cobalt-induced hippocampal epileptiform discharges.
AB  - PURPOSE: To explore the cellular mechanisms of cobalt-induced epileptiform
      discharges in mouse hippocampal slices. METHODS: Hippocampal slices were prepared
      from adult mice and briefly exposed to a CoCl(2)-containing external solution.
      Population and single cell activities were examined via extracellular and whole
      cell patch recordings. RESULTS: Brief cobalt exposure induced spontaneous, ictal
      like discharges originating from the CA3 area. These discharges were suppressed
      by anticonvulsants, gap junction blockers, or by raising extracellular Ca(2+),
      but their generation was not associated with overall hyperexcitability or
      impairment in GABAergic inhibition in the CA3 circuit. Electroencephalographic
      ictal discharges of similar waveforms were observed in behaving rats following
      intrahippocampal cobalt infusion. DISCUSSION: Mechanisms involving activity
      dependent facilitation of gap junctional communication may play a major role in
      cobalt-induced epileptiform discharges.

PMID- 18727681
TI  - Status epilepticus produces chronic alterations in cardiac sympathovagal balance.
AB  - PURPOSE: Status epilepticus (SE) activates the autonomic nervous system,
      increasing sympathetic nervous system control of cardiac function during seizure
      activity. However, lasting effects of SE on autonomic regulation of the heart,
      which may contribute to mortality following seizure activity, are unknown.
      Therefore, autonomic control of cardiac function was assessed following SE.
      METHODS: Using Sprague-Dawley rats after 1-2 weeks of recovery from lithium
      pilocarpine-induced SE or control procedures, we tested overall sympathovagal
      control of the heart, the individual contributions of the sympathetic and
      parasympathetic components of the autonomic nervous system, and baroreflex
      sensitivity. RESULTS: SE induced a chronic shift in sympathovagal balance toward
      sympathetic dominance resulting from decreased parasympathetic activity.
      Baroreflex sensitivity to increased blood pressure was also decreased, likely
      resulting from diminished vagal activation. DISCUSSION: Chronic alterations in
      autonomic regulation of cardiac function, characterized by increased sympathetic
      dominance, occur following SE and likely contribute to subsequent increased
      cardiac risk and mortality.

PMID- 18727682
TI  - Changes in GABAA receptor properties in amygdala kindled animals: in vivo studies
      using [11C]flumazenil and positron emission tomography.
AB  - PURPOSE: The purpose of the present investigation was to quantify alterations in
      GABA(A) receptor density in vivo in rats subjected to amygdala kindling. METHODS:
      The GABA(A) receptor density was quantified by conducting a [(11)C]flumazenil
      (FMZ) positron emission tomography (PET) study according to the full saturation
      method, in which each animal received a single injection of FMZ to fully saturate
      the GABA(A) receptors. Subsequently, the concentration-time curves of FMZ in
      blood [using high-pressure liquid chromatography with UV detector (HPLC-UV) or
      high-performance liquid chromatography coupled to tandem mass spectrometry
      (LC/MS/MS)] and brain (with PET-scanning) were analyzed by population modeling
      using a pharmacokinetic model, containing expressions to describe the time course
      of FMZ in blood and brain. RESULTS: The GABA(A) receptor density (B(max)) in
      kindled rats was decreased by 36% compared with controls. This is consistent with
      a reduction of 28% in electroencephalography (EEG) effect of midazolam in the
      same animal model, suggesting that a reduced number of GABA(A) receptors
      underlies the decreased efficacy of midazolam. Furthermore, receptor affinity
      (K(D)) was not changed, but the total volume of distribution in the brain
      (V(Br)), is increased to 178% of control after kindling, which might indicate an
      alteration in the transport of FMZ across the blood-brain barrier. CONCLUSIONS:
      Both the GABA(A) receptor density (B(max)), and possibly also the blood-brain
      barrier transport of FMZ (V(Br)) are altered after kindling. Furthermore, this
      study indicates the feasibility of conducting PET studies for quantifying
      moderate changes in GABA(A) receptor density in a rat model of epilepsy in vivo.

PMID- 18727683
TI  - Visiting America: notes from an alcohol-focused study tour made in 1961.
AB  - AIMS: This paper has as its focus a study tour made by the author in 1961. Diary
      notes are used to capture a historical moment in the evolution of alcohol
      studies. The paper will argue for the continuing value today of such experiences
      in support of career development and the building of 'the field'. DATA SOURCES:
      Diary notes and personal recollection. FINDINGS: The United States was at the
      time more active than the United Kingdom in its response to alcohol problems.
      There was, however, a disjunction between the elite American research world and
      the world of action, which was not informed greatly by research. For the most
      part, treatment services and prevention strategies seemed driven by opinion
      rather than by evidence. But at the level of serious scientific endeavour there
      was opportunity to meet influential figures including Seldon Bacon, Morris
      Chafetz, Milton Gross, Ebbe Curtis Hoff, Harris Isbell, E. M. Jellinek, Mark
      Keller, Benjamin Kissen, Robert Strauss, Wolf Schmidt and Abraham Wikler, who
      generously made their time available. CONCLUSIONS: These diary notes provide a
      snapshot of a field of endeavour at a critical stage of transition from
      uninformed assumptions towards establishment of a research base which can inform
      public action. The visit was of tangible value to the visitor in several
      different identified ways. Such an experience is inevitably time-bound and
      personal, but there are general conclusions to be drawn as to the benefits which
      will be derived from early travel opportunities in a field such as alcohol
      studies, which is all too easily culture-bound in its horizons and assumptions.
      Alcohol science needs to be more reflective on its history and the mechanisms
      that help to make it happen.

PMID- 18727685
TI  - Minimal enteral feeding reduces the risk of sepsis in feed-intolerant very low
      birth weight newborns.
AB  - AIMS: To evaluate the efficacy and safety of minimal enteral feeding (MEF)
      nutritional practice in feed-intolerant very low birth weight (VLBW) infants.
      METHODS: A retrospective design using data reported in the clinical charts of
      VLBW newborns consecutively observed in neonatal intensive care units (NICU) that
      presents feed intolerance. During the study period, two feeding strategies were
      adopted: total parenteral nutrition (PN) (group 1) or PN plus MEF (group 2), for
      at least 24 h. Primary outcome was the time to reach full enteral feeding;
      secondary outcomes were the occurrence of sepsis, the time to regain birth
      weight, the length of hospitalization, the occurrence of necrotizing
      enterocolitis (NEC) Bell stage >II and death. RESULTS: In total, 102 newborns
      were evaluated: 51 in group 1, and 51 in group 2. Neonates in group 2 achieved
      full enteral nutrition earlier (8 days, interquartile range [IQR] 5) compared
      with subjects receiving total PN (11 days, IQR 5, p < 0.001). A reduction of
      sepsis episodes was observed in group 2 (15.7%) compared with group 1 (33.3%, p =
      0.038). Additionally, subjects in group 2 regained their birth weight and were
      discharged earlier. The occurrence of NEC and death were similar in the two
      groups. CONCLUSION: Minimal enteral feeding in very low birth weight infants
      presenting feed intolerance reduces the time to reach full enteral feeding and
      the risk of sepsis. This feeding practice does not increase the risk of
      necrotizing enterocolitis and death.

PMID- 18727686
TI  - Differing lung function development in infants with univentricular hearts
      compared with healthy infants.
AB  - AIM: To compare the difference in lung function development of healthy controls
      and patients with univentricular hearts from birth prior to surgery and during
      the first year of life when cardiac shunt procedures and the cavopulmonary
      connection are required. METHODS: Tidal flow-volume measurements and single
      occlusion tests were performed from birth serially up to 18 months of age on 28
      unsedated spontaneously breathing infants with univentricular hearts and 58
      healthy control infants. RESULTS: Infants with univentricular heart physiology
      had low tidal volumes, low compliance of the respiratory system and high
      respiratory rate at birth, which over time normalized, whereas the peak
      expiratory flow increased during the study period. The lung function measured at
      birth was predictive of later lung function measurements. CONCLUSION: The pattern
      of lung function development is different in the patients with univentricular
      hearts compared to healthy controls. Lung function measured at birth is
      predictive of later lung function.

PMID- 18727687
TI  - Preparing for your next shift: check bias at the door.

PMID- 18727688
TI  - The role of GABRA2 in alcohol dependence, smoking, and illicit drug use in an
      Australian population sample.
AB  - BACKGROUND: Multiple studies have shown that genetic variation in the alpha-2
      subunit of the gamma-aminobutyric acid type A (GABA(A)) receptor (GABRA2) is
      associated with risk for alcohol dependence. Recent reports have suggested that
      GABRA2 may exert its influence on dependence through factors such as sensitivity
      to alcohol's intoxicating effects and that GABRA2 may also contribute to a common
      underlying genetic vulnerability to both alcohol and drug dependence. The present
      study tested for association between GABRA2 and alcohol dependence, smoking, and
      illicit drug use within the Australian population. METHODS: We genotyped 11
      single nucleotide polymorphisms (SNPs) within or flanking GABRA2 in 4597 subjects
      (34.6% males) from 2618 families comprising 814 monozygotic pairs, 1177 dizygotic
      pairs, and 627 twins whose co-twin did not participate. Family-based association
      tests were conducted for binary and quantitative measures of alcohol dependence,
      smoking, and cannabis and other illicit drug use. RESULTS: We observed evidence
      of association (p < 0.05) between multiple GABRA2 SNPs and quantitative measures
      of alcohol dependence, including symptom scores and principal component factor
      scores from the 9 criteria for DSM-IV alcohol dependence, in the opposite
      direction to that previously reported. In contrast, GABRA2 was not associated
      overall with dichotomous measure of alcohol dependence nor with smoking,
      cannabis, or illicit drug use. CONCLUSIONS: The GABRA2 allelic associations found
      in clinical case-control studies have detectable but minor effects on DSM-defined
      alcohol dependence in the general community. Systematic comparisons of allelic
      effects on alcohol dependence in clinical cases and in the general community are
      required.

PMID- 18727689
TI  - Long-term antidepressant treatment in bipolar disorder: meta-analyses of benefits
      and risks.
AB  - OBJECTIVE: Long-term antidepressant (AD) treatment for depression in bipolar
      disorder (BPD) patients is highly prevalent, but its benefits and risks remain
      uncertain, encouraging this meta-analysis of available research. METHOD: We
      reviewed randomized controlled trials for BPD involving >or=6 months of treatment
      with AD +/- mood stabilizer (MS) vs. placebo +/- MS, using meta-analyses to
      compare reported risks of new depression vs. mania. RESULTS: In seven trials (350
      BPD patients) involving 12 contrasts, long-term treatments that included ADs
      yielded 27% lower risk of new depression vs. MS-only or no treatment [pooled
      relative risk, RR = 0.73; 95% CI 0.55-0.97; number-needed-to-treat (NNT) = 11],
      but 72% greater risk for new mania [RR = 1.72; 95% CI 1.23-2.41; number-needed-to
      harm (NNH) = 7]. Compared with giving an MS-alone, adding an AD yielded neither
      major protection from depression (RR = 0.84; 95% CI 0.56-1.27; NNT = 16) nor
      substantial increase in risk of mania (RR = 1.37; 95% CI 0.81-2.33; NNH = 16).
      CONCLUSION: Long-term adjunctive AD treatment was not superior to MS-alone in
      BPD, further encouraging reliance on MSs as the cornerstone of prophylaxis.

PMID- 18727691
TI  - Screening of organ and tissue donors for West Nile virus by nucleic acid
      amplification--a three year experience in Alberta.
AB  - West Nile Virus (WNV)-specific nucleic acid amplification testing (NAAT) of organ
      and tissue donors remains controversial. We report three years of WNV donor
      screening in Alberta Canada using NAAT. Between 2003 and 2005, 1549 initial
      specimens were received. A valid negative result was issued within the specified
      turnaround time on 1531 (98.8%). The initial NAAT was successful for 1393 samples
      (90%), while repeat testing using an alternate NAAT resolved a further 126
      samples. For 12 of 14 donors, a second specimen provided a valid negative result.
      Failure to generate a valid negative result in time resulted in rescheduling of
      one living related organ transplant, and surgery proceeded in the absence of a
      final result in one multi-organ donation after risk assessment. For 11 tissue
      donors, tissues were discarded due to lack of a WNV result. Invalid results
      usually occurred on postmortem haemolyzed tissue donor samples due to inhibitory
      reactions. There were no confirmed positive donors, no false-positive results and
      no solid organs lost due to WNV testing. We conclude that WNV NAAT of organ and
      tissue donors can be implemented without compromising availability of donors but
      requires committed laboratory support.

PMID- 18727692
TI  - Alexis Carrel: genius, innovator and ideologist.
AB  - Alexis Carrel was a Frenchman from Lyon, who gained fame at the Rockefeller
      Institute in New York at the beginning of the 20th century. He was the first to
      demonstrate that arteriovenous anastomoses were possible. Alexis Carrel was
      awarded the Nobel Prize for his contributions to vascular surgery and
      transplantation in 1912. He was a versatile scientist, who made numerous
      discoveries from the design of an antiseptic solution to treat injuries during
      the First World War to tissue culture and engineering, and organ preservation,
      making him the father of solid organ transplantation. Together, with the famous
      aviator and engineer Charles Lindbergh, they were the first scientists capable of
      keeping an entire organ alive outside of the body, using a perfusion machine. Due
      to his many dubious ideas and his association with fascism in the 1930s and
      during the Second World War, many of his scientific achievements have been
      forgotten today and taken for granted.

PMID- 18727693
TI  - AJT's response to the National Institutes of Health public access regulations.

PMID- 18727690
TI  - A role for mannose-binding lectin, a component of the innate immune system in pre
      eclampsia.
AB  - PROBLEM: Mannose-binding lectin (MBL) is a pattern-recognition receptor that
      activates complement and modulates inflammation. Homozygosity for the most common
      allele of the MBL2 gene that is associated with high MBL serum concentrations is
      more prevalent among patients with pre-eclampsia. The objective of this study was
      to determine maternal plasma MBL concentrations in normal pregnant women and
      patients with pre-eclampsia. METHOD OF STUDY: This cross-sectional study included
      normal pregnant women (n = 187) and patients with pre-eclampsia (n = 99).
      Maternal plasma MBL concentrations were determined by ELISA. RESULTS: Women with
      pre-eclampsia had a higher median maternal plasma MBL concentration than normal
      pregnant women. MBL concentration distribution curves were three-modal, the
      subintervals in normal pregnancy were low (< 143.7), intermediate (143.7-1898.9)
      and high (> 1898.9 ng/mL). The proportion of normal pregnant women was larger in
      the low subinterval, while the proportion of patients with preeclampsia was
      larger in the high subinterval (P = 0.02). Normal pregnant women in the high
      subinterval had a larger rate of placental underperfusion than those in the low
      and intermediate subintervals (P = 0.02). CONCLUSIONS: The median maternal plasma
      MBL concentration is elevated in patients with pre-eclampsia and a larger
      proportion of these patients are in the high subinterval than normal pregnant
      women, suggesting that this component of the innate immune system is involved in
      the mechanisms of disease in pre-eclampsia.

PMID- 18727694
TI  - Impact of pegylated interferon and ribavirin treatment on graft survival in liver
      transplant patients with recurrent hepatitis C infection.
AB  - Recurrent hepatitis C virus (HCV) infection is a major cause of morbidity and
      mortality after liver transplantation for HCV-related end stage liver disease.
      Although previous studies have shown a short-term effect of interferon-based
      treatment on fibrosis progression, it is unclear whether this translates to
      improved graft survival. We evaluated whether treatment of recurrent HCV leads to
      an improved graft survival. Cohort study included consecutive HCV patients who
      underwent liver transplantation between 1 January 1995 and 1 January 2005 in the
      Mayo Clinic, Rochester, MN. Two hundred and fifteen patients were included in the
      study. During a median follow-up of 4.4 years (interquartile range 2.2-6.6), 165
      patients (77%) had biopsy-proven recurrent HCV infection confirmed by serum HCV
      RNA testing. Seventy-eight patients were treated. There were no differences in
      MELD-score, fibrosis stage or time towards HCV recurrence between treated and
      untreated patients at time of recurrence. There was a trend for greater frequency
      of acute cellular rejection among untreated patients. The incidence of graft
      failure was lower for patients treated within 6 months of recurrence compared to
      patients not treated within this time-period (log rank p = 0.002). Time-dependent
      multivariate Cox regression analysis showed that treatment of recurrent HCV
      infection was statistically significantly associated with a decreased risk of
      overall graft failure (hazard ratio 0.34; CI 0.15-0.77, p = 0.009) and a
      decreased risk of graft failure due to recurrent HCV (hazard ratio 0.24; CI 0.08
      0.69, p = 0.008). In conclusion, although a cause and effect relationship cannot
      be established, treatment of recurrent HCV infection after liver transplantation
      is associated with a reduced risk of graft failure.

PMID- 18727695
TI  - Substantial variation in the acceptance of medically complex live kidney donors
      across US renal transplant centers.
AB  - Concern exists about accepting live kidney donation from 'medically complex
      donors'--those with risk factors for future kidney disease. This study's aim was
      to examine variation in complex kidney donor use across US transplant centers. We
      conducted a retrospective cohort study of live kidney donors using organ
      procurement and transplantation network data. Donors with hypertension, obesity
      or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) were
      considered medically complex. Among 9319 donors, 2254 (24.2%) were complex: 1194
      (12.8%) were obese, 956 (10.3%) hypertensive and 392 (4.2%) had low eGFR. The
      mean proportion of medically complex donors at a center was 24% (range 0-65%). In
      multivariate analysis, donor characteristics associated with medical complexity
      included spousal relationship to the recipient (OR 1.29, CI 1.06-1.56, p < 0.01),
      low education (OR 1.19, CI 1.04-1.37, p = 0.01), older age (OR 1.01 per year, CI
      1.01-1.02, p < 0.01) and non-US citizenship (OR 0.70, CI 0.51-0.97, p = 0.03).
      Renal transplant centers with the highest transplant volume (OR 1.26, CI 1.02
      1.57, p = 0.03), and with a higher proportion of (living donation)/(all kidney
      transplants) (OR 1.97, CI 1.23-3.16, p < 0.01) were more likely to use medically
      complex donors. Though controversial, the use of medically complex donors is
      widespread and varies widely across centers.

PMID- 18727696
TI  - Portal vein complications in pediatric living donor liver transplantation using
      left-side grafts.
AB  - The aim of this report is to assess the rate of portal vein complications (PVCs),
      the success rate of treatment for PVCs and the prognosis of patients with PVCs
      for pediatric living donor liver transplantation (LDLT). Pre- and postoperative
      records of 521 pediatric LDLTs, using left-side grafts were retrospectively
      reviewed. The overall rate of PVC was 9%, with early PVC occurring in nine
      patients (1.7%) with a mortality rate of 67% and late PVC in 38 patients (7.3%).
      Fifteen of these patients with late PVC showed complete portal vein occlusion
      despite various treatments, and in six of them the graft was lost. Histological
      examination revealed fibrosis in portal areas in 13 patients, around the central
      veins associated with cholestasis in the parenchyma in 10, and hepatocyte
      ballooning in 12. Correction of portal vein flow or retransplantation is
      necessary for the rescue of patients with early PVCs. Graft loss in the long term
      may be high with the occurrence of liver failure or portal hypertension related
      causes, such as hepatopulmonary syndrome and gastrointestinal bleeding in
      patients with late PVCs. For the rescue of these patients, especially for
      patients with body weight < 6 kg, regular monitoring of portal vein flow is
      essential.

PMID- 18727697
TI  - Hydrogen inhalation ameliorates oxidative stress in transplantation induced
      intestinal graft injury.
AB  - Ischemia/reperfusion (I/R) injury during small intestinal transplantation (SITx)
      frequently causes complications including dysmotility, inflammation and organ
      failure. Recent evidence indicates hydrogen inhalation eliminates toxic hydroxyl
      radicals. Syngeneic, orthotopic SITx was performed in Lewis rats with 3 h of cold
      ischemic time. Both donor and recipient received perioperative air or 2% hydrogen
      inhalation. SITx caused a delay in gastrointestinal transit and decreased jejunal
      circular muscle contractile activity 24 h after surgery. Hydrogen treatment
      resulted in significantly improved gastrointestinal transit, as well as jejunal
      smooth muscle contractility in response to bethanechol. The transplant induced
      upregulation in the inflammatory mediators CCL2, IL-1 beta, IL-6 and TNF-alpha
      were mitigated by hydrogen. Hydrogen significantly diminished lipid peroxidation
      compared to elevated tissue malondialdehyde levels in air-treated grafts
      demonstrating an antioxidant effect. Histopathological mucosal erosion and
      increased gut permeability indicated a breakdown in posttransplant mucosal
      barrier function which was significantly attenuated by hydrogen treatment. In
      recipient lung, hydrogen treatment also resulted in a significant abatement in
      inflammatory mRNA induction and reduced neutrophil recruitment. Hydrogen
      inhalation significantly ameliorates intestinal transplant injury and prevents
      remote organ inflammation via its antioxidant effects. Administration of
      perioperative hydrogen gas may be a potent and clinically applicable therapeutic
      strategy for intestinal I/R injury.

PMID- 18727698
TI  - Superagonistic CD28 antibody induces donor-specific tolerance in rat renal
      allografts.
AB  - The ultimate goal of organ transplantation is to establish graft tolerance where
      CD4+CD25+FOXP3+ regulatory T (Treg) cells play an important role. We examined
      whether a superagonistic monoclonal antibody specific for CD28 (CD28 SA), which
      expands Treg cells in vivo, would prevent acute rejection and induce tolerance
      using our established rat acute renal allograft model (Wistar to Lewis). In the
      untreated or mouse IgG-treated recipients, graft function significantly
      deteriorated with marked destruction of renal tissue, and all rats died by 13
      days with severe azotemia. In contrast, 90% of recipients treated with CD28 SA
      survived over 100 days, and 70% survived with well-preserved graft function until
      graft recovery at 180 days. Analysis by flow cytometry and immunohistochemistry
      demonstrated that CD28 SA induced marked infiltration of FOXP3+ Treg cells into
      the allografts. Furthermore, these long-surviving recipients showed donor
      specific tolerance, accepting secondary (donor-matched) Wistar cardiac
      allografts, but acutely rejecting third-party BN allografts. We further
      demonstrated that adoptive transfer of CD4+CD25+ Treg cells, purified from CD28
      SA-treated Lewis rats, significantly prolonged allograft survival and succeeded
      in inducing donor-specific tolerance. In conclusion, CD28 SA treatment
      successfully induces donor-specific tolerance with the involvement of Treg cells,
      and thus the therapeutic value of this approach warrants further investigation
      and preclinical studies.

PMID- 18727699
TI  - Association between primary graft dysfunction among lung, kidney and heart
      recipients from the same multiorgan donor.
AB  - Even organs from an ideal donor will occasionally develop primary graft
      dysfunction (PGD) causing a significant morbidity and mortality after
      transplantation. It is likely that this situation represents subtle undetectable
      levels of ongoing donor organ dysfunction. The aim of this study is to
      investigate the association of PGD between lung, kidney and heart recipients from
      the one donor. From 202 multiorgan donors, contributed 231 consecutive lung
      transplants at the Alfred Hospital, 378 kidney and 114 heart transplants were
      subsequently performed at multiple centers across Australia and New Zealand.
      Eight hundred seventy-five organs were used for 723 transplants. The incidence of
      PGD after lung, kidney and heart transplants was 20% (47/231), 24% (92/378) and
      20% (23/114), respectively. In paired single organ recipients, PGD in one of the
      pair was a significant risk factor for the development of PGD in the other [lung:
      odds ratio = 5.63 (1.72-18.43), p = 0.004; kidney: odds ratio = 3.19 (1.90-5.35),
      p < 0.0001]. In multivariate analysis, same donor heart PGD [3.37 (1.19-9.50), p
      = 0.02] was an independent risk factor for lung PGD and same donor lung PGD was
      significant risk factor for kidney PGD [1.94 (1.01-3.73), p = 0.04], if the PGD
      status of the paired kidney was not known. There was a significant association
      for the development of PGD across different organs transplanted from the same
      donor.

PMID- 18727700
TI  - Nephrectomy elicits impact of age and BMI on renal hemodynamics: lower
      postdonation reserve capacity in older or overweight kidney donors.
AB  - Renal functional reserve could be relevant for the maintenance of renal function
      after kidney donation. Low-dose dopamine induces renal vasodilation with a rise
      in glomerular filtration rate (GFR) in healthy subjects and is thought to be a
      reflection of reserve capacity (RC). Older age and higher body mass index (BMI)
      may be associated with reduced RC. We therefore investigated RC in 178
      consecutive living kidney donors (39% males, age 48 +/- 11 years, BMI 25.5 +/-
      4.1). RC was determined as the rise in GFR ((125)I-iothalamate), 4 months before
      and 2 months after donor nephrectomy. Before donor nephrectomy, GFR was 114 +/-
      20 mL/min, with a reduction to 72 +/- 12 mL/min after donor nephrectomy. The
      dopamine-induced rise in GFR of 11 +/- 10% was reduced to 5 +/- 7% after donor
      nephrectomy (p < 0.001). Before donor nephrectomy, older age and higher BMI did
      not affect reserve capacity. After donor nephrectomy, the response of GFR to
      dopamine independently and negatively correlated with older age and higher BMI.
      Moreover, postdonation reserve capacity was absent in obese donors. The presence
      of overweight had more impact on loss of RC in younger donors. In conclusion,
      donor nephrectomy unmasked an age- and overweight-induced loss of reserve
      capacity. Younger donors with obesity should be carefully monitored.

PMID- 18727701
TI  - Impact of human donor lung gene expression profiles on survival after lung
      transplantation: a case-control study.
AB  - Primary graft dysfunction (PGD) continues to be a major cause of early death
      after lung transplantation. Moreover, there remains a lack of accurate
      pretransplant molecular markers for predicting PGD. To identify distinctive donor
      lung gene expression signatures associated with PGD, we profiled human donor
      lungs using microarray technology prior to implantation. The genomic profiles of
      10 donor lung samples from patients who subsequently developed clinically defined
      severe PGD were compared with 16 case-matched donor lung samples from those who
      had a favorable outcome without PGD (development set, n = 26). Selected PCR
      validated predictive genes were tested by quantitative reverse transcription
      polymerase chain reaction in an independent test set (n = 81). Our microarray
      analyses of the development set identified four significantly upregulated genes
      (ATP11B, FGFR2, EGLN1 and MCPH1) in the PGD samples. These genes were also
      significantly upregulated in donor samples of the test set of patients with poor
      outcomes when compared to those of patients with good outcomes after lung
      transplantation. This type of biological donor lung assessment shows significant
      promise for development of a more accurate diagnostic strategy to assess donor
      lungs prior to implantation.

PMID- 18727702
TI  - Liver transplantation for hepatocellular carcinoma: beyond the Milan criteria.
AB  - Liver transplantation represents a cornerstone in the management of early-stage
      hepatocellular carcinoma (HCC). Expansion beyond the Milan criteria for liver
      transplantation (1 lesion <or= 5 cm, or 2 to 3 lesions each <or= 3 cm) remains
      controversial. This review covers several key areas: (1) Recent developments and
      published data on expanded criteria for deceased donor and live-donor liver
      transplantation, with emphasis on criteria that have been applied to preoperative
      imaging. (2) Independent testing of expanded criteria, where published data are
      largely limited to the proposed University of California, San Francisco criteria
      (1 lesion <or= 6.5 cm, 2-3 lesions each <or= 4.5 cm with total tumor diameter
      <or= 8 cm). (3) Response to loco-regional therapy and tumor downstaging. (4) The
      fundamental questions and answers in resolving the controversy over expanded
      criteria. The key issue pertains to whether acceptable outcome can be achieved on
      a broader scale beyond single center experience, which appears to support modest
      expansion beyond the Milan criteria. The foundation of the debate over expanded
      criteria may rest upon what the transplant community would consider to be the
      acceptable threshold for patient survival using expanded criteria, without
      causing significant harm to other transplant candidates without HCC.

PMID- 18727703
TI  - Sequential pancreaticoduodenectomy after living donor liver transplantation for
      cholangiocarcinoma.
AB  - Liver transplantation (LT) for patients with primary sclerosing cholangitis (PSC)
      is often contraindicated due to concomitant occurrence of cholangiocarcinoma
      (CC). Cases of simultaneous pancreaticoduodenectomy (PD) with LT have been
      sporadically reported; however, the applicability of such an invasive procedure
      to patients with CC has not been validated. We report here a case of sequential
      PD performed 44 days after a successful living donor liver transplantation (LDLT)
      using a left lobe graft. Although a clear pancreatic juice leakage through the
      drain persisted for days after surgery, the patient recovered from the
      complication and was discharged 32 days after the procedure. Currently, 1 year
      after LDLT, the patient is doing well with no evidence of recurrence. In
      conclusion, a sequential PD following LDLT is a safe and feasible option to treat
      CC complicating PSC. Long-term follow-up and accumulation of cases are necessary
      to evaluate the effectiveness of this procedure for this complicated disease.

PMID- 18727704
TI  - Variation in mitochondrial genotype has substantial lifespan effects which may be
      modulated by nuclear background.
AB  - Mitochondria are thought to play a central role in aging. In humans, specific
      naturally occurring mitochondrial genetic variants are overrepresented among
      centenarians, but only in certain populations; therefore, we cannot tell whether
      this effect is due solely to mitochondrial genetics or to nuclear-mitochondrial
      gene complexes, nor do we know the magnitude of the effect in terms we can relate
      to, such as mean lifespan differences. To examine the effects of natural
      mitochondrial DNA (mtDNA) variation on lifespan, we need to vary the
      mitochondrial genotype while controlling the nuclear genotype. Here, nuclear
      genome replacement is achieved using strains of Drosophila melanogaster bearing
      multiply inverted 'balancer' chromosomes that suppress recombination, and an
      isogenic donor strain, thus forcing replacement of entire chromosomes in a single
      cross while suppressing recombination. Lifespans of wild-type mtDNA variants on
      the chromosome replacement background vary substantially, and sequencing of the
      entire protein coding mitochondrial genomes indicates that these lifespan
      differences are sometimes associated with single amino acid differences. On other
      nuclear genetic backgrounds, the magnitude and direction of these lifespan
      effects can change dramatically, and this can be due to changes in baseline
      mortality risk, rate of aging and/or time of onset of aging. The limited mtDNA
      variation in D. melanogaster makes it an ideal organism for biochemical studies
      to link genotype and aging phenotype.

PMID- 18727705
TI  - Reference limits of serum TSH and free T4 are significantly influenced by race
      and age in an urban outpatient medical practice.
AB  - OBJECTIVE: The suitability of TSH reference limits derived from national
      databases to outpatient practices has not been established. We aimed to determine
      whether race and age influence the distribution of TSH and free T4 (fT4). DESIGN:
      A cross-sectional study of an urban outpatient medical practice. PARTICIPANTS:
      Patients (n = 22,116) without clinical evidence of thyroid disease or use of
      thyroid-specific medications. MEASUREMENTS: Comparison of TSH and fT4
      distributions in specific racial and age groups including blacks, whites and
      Hispanics. RESULTS: TSH was distributed at higher concentrations, without skew,
      in whites compared to blacks (median, 1.54 mIU/l vs. 1.18 mIU/l, P < 0.001) and
      in old (>80 years old) compared to young (20-29 years old) (median, 1.61 mIU/l
      vs. 1.13 mIU/l, P < 0.001). In all patients, blacks and whites, 3%, 8% and 5%,
      respectively, of those aged > 80 years were misclassified as having high TSH
      compared to those aged 20-29 years (P < 0.001). Using TSH limits from national
      databases resulted in significant misclassification of patients with raised or
      lowered TSH. Mean fT4 was significantly lower in blacks than whites (17.5 +/-
      4.38 pmol/l vs. 18.3 +/- 3.99 pmol/l, P < 0.001), did not differ between young
      and old, but decreased progressively (average 7%) as TSH increased to > 4.5
      mIU/l. CONCLUSIONS: Reference limits for TSH differ between races and with age.
      Use of race- and age-specific reference limits decreases misclassification of
      patients with lowered or raised TSH in an urban practice. The unique fT4:TSH
      relationships of blacks and whites may be genetically determined. The
      implications of the small decrement in fT4 as TSH increases remain to be
      explored.

PMID- 18727706
TI  - Relationship between clinical features and gastric emptying disturbances in
      diabetes mellitus.
AB  - BACKGROUND AND OBJECTIVES: Gastric emptying (GE) may be delayed or rapid in
      diabetes mellitus. We sought to ascertain differences in risk factors or
      associated features (i.e. diabetic 'phenotype') among patients with diabetes who
      have rapid, slow or normal GE. METHODS: From a database of patients in whom
      gastrointestinal transit was assessed by scintigraphy, we compared the diabetic
      phenotype in diabetic patients with rapid, slow and normal GE. RESULTS: Of 129
      patients, 55 (42%) had normal, 46 (36%) had delayed and 28 (22%) patients had
      rapid GE. In each GE category, there was an approximately equal number of type 1
      and type 2 diabetes. In multivariable analyses, significant weight loss (OR,
      2.81; 95% CI, 1.09-7.23) and neuropathy (OR, 3.60; 95% CI, 1.007-12.89) were the
      risk factors for delayed and rapid GE, respectively. Insulin therapy (OR, 0.08;
      95% CI, 0.01-0.53) was associated with a lower risk of rapid compared to normal
      GE. However, other manifestations or characteristics of the diabetes 'phenotype'
      (i.e. type and duration of diabetes, glycosylated haemoglobin levels, and
      extraintestinal complications) were not useful for discriminating normal from
      delayed or rapid GE. At a specificity of 60%, clinical features were 73%
      sensitive for discriminating between normal and delayed GE and 80% sensitive for
      discriminating normal from rapid GE. CONCLUSIONS: Diabetes is associated with
      slow and rapid GE. Because the diabetic phenotype is of limited utility for
      identifying disordered GE, GE should be assessed in patients with diabetes and
      gastrointestinal symptoms.

PMID- 18727707
TI  - Benzofuran derivatives and the thyroid.
AB  - Amiodarone and dronedarone are two clinically important benzofuran derivatives.
      Amiodarone has been used widely for treating resistant tachyarrhythmias in the
      past three decades. However amiodarone and its main metabolically active
      metabolite desethylamiodarone can adversely affect many organs, including the
      thyroid gland. Amiodarone-induced thyroid disorders are common and often present
      as a management challenge for endocrinologists. The pathogenesis of amiodarone
      induced thyroid dysfunction is complex but the inherent effects of the drug
      itself as well as its high iodine content appear to play a central role. The non
      iodinated dronedarone also exhibits anti-arrhythmic properties but appears to be
      less toxic to the thyroid. This review describes the biochemistry of benzofuran
      derivatives, including their pharmacology and the physiology necessary for
      understanding the cellular mechanisms involved in their actions. The known
      effects of these compounds on thyroid action are described. Recommendations for
      management of amiodarone-induced hypothyroidism and thyrotoxicosis are suggested.
      Dronedarone appears to be an alternative but less-effective anti-arrhythmic agent
      and it does not have adverse effects on thyroid function. It may have a future
      role as an alternative agent in patients being considered for amiodarone therapy
      especially those at high risk of developing thyroid dysfunction but not in severe
      heart failure.

PMID- 18727709
TI  - Serum total antioxidant status and lipid peroxidation marker malondialdehyde
      levels in overt and subclinical hypothyroidism.
AB  - BACKGROUND: Mitochondria are the main production site of free oxygen radicals,
      which can cause organ dysfunction by oxidation of cellular macromolecules such as
      carbohydrates, lipids and proteins. Oxidative stress may result from either
      overproduction of these species or from failure of the antioxidant defence
      systems. Thyroid hormones have well-known effects on mitochondrial oxygen
      consumption, but data about how hypothyroidism affects oxidative stress are
      controversial, and little is known about oxidative stress in subclinical
      hypothyroidism. Total antioxidant status (TAS) gives information about all of the
      antioxidants in the organism, while malondialdehyde (MDA) is a lipid peroxidation
      marker used to assess lipid peroxidation due to increased oxidative stress. We
      aimed to determine how hypothyroidism and subclinical hypothyroidism affect serum
      MDA and TAS. SUBJECTS AND METHODS: Serum TAS, MDA, C-reactive protein levels and
      lipid compositions were studied in 20 hypothyroid, 40 subclinical hypothyroid and
      40 healthy subjects. RESULTS: MDA was elevated in both hypothyroid and
      subclinical hypothyroid patients compared with controls, while TAS levels show no
      significant differences between groups. Low-density lipoprotein (LDL) cholesterol
      levels were significantly high in both hypothyroid and subclinical hypothyroid
      patients. Triglyceride levels were high only in hypothyroid patients when
      compared with the controls. MDA showed a correlation with LDL cholesterol, total
      cholesterol and triglyceride. CONCLUSIONS: These results suggest an increased
      oxidative stress in both hypothyroid and subclinical hypothyroidism states, which
      can be explained by both the insufficient increase in the antioxidant status and
      the altered lipid metabolism in these cases.

PMID- 18727710
TI  - Voice characteristics in women with congenital adrenal hyperplasia due to 21
      hydroxylase deficiency.
AB  - OBJECTIVE: Congenital adrenal hyperplasia (CAH) is an autosomal recessive
      inherited disorder resulting in lack of cortisol and often aldosterone and
      overproduction of androgens. Raised levels of androgens can lead to increased
      mass in the laryngeal tissues, which may lower the fundamental frequency (F0) of
      the voice. DESIGN/PATIENTS: A follow-up study of voice characteristics in 38
      women with CAH and 24 age-matched controls between 18 and 63 years of age using
      subjective self-ratings of voice symptoms and acoustic and perceptual analyses.
      The results were correlated to mutation and treatment. MEASUREMENTS: The subjects
      rated degree of hoarseness, dark voice, voice problems and vocal fatigue on
      visual analogue scales. Audio recordings were made of a standard reading passage
      in a sound treated booth. Acoustic analyses were made of the subjects' mean,
      minimum and maximum F0 in the habitual speech range. Three voice clinicians made
      perceptual evaluations of dark voice in terms of timbre. RESULTS: Women with CAH
      rated higher values than controls with regard to the statement 'my voice is a
      problem in my daily life'. They spoke with significantly lower mean, lower
      minimum and lower maximum F0, as well as darker voice quality as compared with
      the controls. Affected voice symptoms were associated with a late diagnosis or
      problems with medication. CONCLUSION: The voices in women with CAH can be
      virilized because of late diagnosis or suboptimal treatment with glucocorticoids.
      These voice problems may need referral for voice assessment and should be
      considered when treating CAH.

PMID- 18727708
TI  - Down-regulation of NR4A1 in follicular thyroid carcinomas is restored following
      lithium treatment.
AB  - INTRODUCTION: The identification of follicular thyroid adenoma-associated
      transcripts will lead to a better understanding of the events involved in
      pathogenesis and progression of follicular tumours. Using Serial Analysis of Gene
      Expression, we identified five genes that are absent in a malignant follicular
      thyroid carcinoma (FTC) library, but expressed in follicular adenoma (FTA) and
      normal thyroid libraries. METHODS: NR4A1, one of the five genes, was validated in
      a set of 27 normal thyroid tissues, 10 FTAs and 14 FTCs and three thyroid
      carcinoma cell lines by real time PCR. NR4A1 can be transiently increased by a
      variety of stimuli, including lithium, which is used as adjuvant therapy of
      thyroid carcinoma with (131)I. We tested if lithium could restore NR4A1
      expression. The expression of other genes potentially involved in the same
      signalling pathway was tested. To this end, lithium was used at different
      concentration (10 mm or 20 mm) and time (2 h and 24 h) and the level of
      expression was tested by quantitative PCR. We next tested if Lithium could affect
      cell growth and apoptosis. RESULTS: We observed that NR4A1 expression was under
      expressed in most of the FTCs investigated, compared with expression in normal
      thyroid tissues and FTAs. We also found a positive correlation between NR4A1 and
      FOSB gene expression. Lithium induced NR4A1 and FOSB expression, reduced CCDN1
      expression, inhibited cell growth and triggered apoptosis in a FTC cell line.
      CONCLUSIONS: NR4A1 is under-expressed in most of FTCs. The loss of expression of
      both NR4A1 and the Wnt pathway gene FOSB was correlated with malignancy. This is
      consistent with the hypothesis that its loss of expression is part of the
      transformation process of FTCs, either as a direct or indirect consequence of Wnt
      pathway alterations. Lithium restores NR4A1 expression, induces apoptosis and
      reduces cell growth. These findings may explain a possible molecular mechanism of
      lithium's therapeutic action.

PMID- 18727711
TI  - Anaemia and marrow fibrosis in patients with primary hyperparathyroidism before
      and after curative parathyroidectomy.
AB  - OBJECTIVE: To determine the relationship between anaemia and myelofibrosis in
      patients with symptomatic primary hyperparathyroidism (PHPT) and to assess the
      effect of curative parathyroidectomy on anaemia and marrow fibrosis. DESIGN AND
      METHODS: In this prospective follow-up study of 28 consecutive patients with
      symptomatic PHPT from January 2005 to June 2006, 15 patients were diagnosed with
      anaemia (haemoglobin < 130 g/l in males and < 120 g/l in females), eight (53%) of
      whom were finally recruited for the study. Complete blood cell count, serum
      calcium, phosphorus, alkaline phosphatase, intact PTH and 25-hydroxyvitamin D and
      bone marrow examination were performed both before and after parathyroidectomy in
      all (n = 8) patients, but bone marrow examination after surgery was performed
      only in those who had marrow fibrosis at baseline (n = 6). RESULTS: Anaemia was
      observed in 15 (53.3%) of the 28 patients with symptomatic PHPT. Normocytic
      normochromic anaemia that is characteristic of PHPT was found in 14 (50%)
      patients. Eight of the 15 patients with anaemia had a bone marrow examination and
      marrow fibrosis was observed in six (75%). Both anaemia and marrow fibrosis
      improved after successful parathyroidectomy, but improvement in anaemia was
      significant (P = 0.02) only in those with marrow fibrosis at baseline. Marrow
      fibrosis did not correlate with duration of the disease (P = 0.17), degree of
      hypercalcaemia (P = 0.53) or serum levels of intact PTH (P = 0.60). CONCLUSIONS:
      Anaemia is common in patients with symptomatic PHPT, and was associated with
      marrow fibrosis in the majority of the patients who underwent bone biopsy. Both
      anaemia and marrow fibrosis improved after curative parathyroidectomy, but
      improvement in anaemia was noticeable only in those who had marrow fibrosis at
      presentation.

PMID- 18727712
TI  - Increased death risk and altered cancer incidence pattern in patients with
      isolated or combined autoimmune primary adrenocortical insufficiency.
AB  - OBJECTIVES: Primary adrenocortical insufficiency is mostly caused by an
      autoimmune destruction of the adrenal cortex. The disease may appear isolated or
      as a part of an autoimmune polyendocrine syndrome (APS). APS1 is a rare
      hereditary disorder with a broad spectrum of clinical manifestations. In APS2,
      primary adrenocortical insufficiency is often combined with autoimmune thyroid
      disease and/or type 1 diabetes. We analysed mortality and cancer incidence in
      primary adrenocortical insufficiency patients during 40 years. Data were compared
      with the general Swedish population. DESIGN AND PATIENTS: A population based
      cohort study including all patients with autoimmune primary adrenocortical
      insufficiency (3299) admitted to Swedish hospitals 1964-2004. MEASUREMENTS:
      Mortality risk was calculated as the standardized mortality ratio (SMR) and
      cancer incidence as the standardized incidence ratio (SIR). RESULTS: A more than
      2-fold increased mortality risk was observed in both women (SMR 2.9, 95% CI 2.7
      3.0) and men (SMR 2.5, 95% CI 2.3-2.7). Highest risks were observed in patients
      diagnosed in childhood. SMR was higher in APS1 patients (SMR 4.6, 95% CI 3.5-6.0)
      compared with patients with APS2 (SMR 2.1, 95% CI 1.9-2.4). Cancer incidence was
      increased (SIR 1.3, 95% CI 1.2-1.5). When tumours observed during the first year
      of follow-up were excluded, only the cancer risk among APS1 patients remained
      increased. Cause-specific cancer incidence analysis revealed significantly higher
      incidences of oral cancer, nonmelanoma skin cancer, and male genital system
      cancer among patients. Breast cancer incidence was lower than in the general
      population. CONCLUSIONS: Our study shows a reduced life expectancy and altered
      cancer incidence pattern in patients with autoimmune primary adrenocortical
      insufficiency.

PMID- 18727713
TI  - Functional studies of new TSH receptor (TSHr) mutations identified in patients
      affected by hypothyroidism or isolated hyperthyrotrophinaemia.
AB  - OBJECTIVES: To establish the role of new TSH receptor (TSHr) variants (P27T, E34
      K, R46P, D403N, W488R and M527T) recently identified in children with congenital
      hypothyroidism (CH) or subclinical hypothyroidism (SH) with a thyroid gland of
      normal size. DESIGN AND MEASUREMENTS: TSHr variants were obtained by mutagenesis.
      Wild-type (wt) and TSHr mutants were expressed in COS cells and cAMP assay,
      (125)I-TSH binding and microchip flow cytometry analyses were performed. RESULTS:
      D403N and M527T mutants showed a lower cAMP response to bovine TSH (bTSH) with
      respect to the wtTSHr. R46P and W488R mutants did not show any response to bTSH
      stimulation in terms of cAMP production. The E34 K mutant showed a significantly
      lower cAMP response to stimulation with bTSH, while P27T had a lower cAMP
      response only to the highest dose of bTSH used. P27T, E34 K, D403N and M527T
      mutants showed a lower TSH binding capacity with respect to the wtTSHr. R46P and
      W488R mutants did not show any TSH binding. CONCLUSIONS: E34 K, D403N, M527T,
      R46P and W488R TSHr variants seem to cause a functional abnormality of the
      receptor which is responsible for the observed phenotype. The P27T TSHr variant
      does not seem to play a functional role in the pathogenesis of CH and should be
      considered as a polymorphism.

PMID- 18727715
TI  - Systematic review of laparoscopic vs open colonic surgery within an enhanced
      recovery programme.
AB  - BACKGROUND: Fast track surgery accelerates recovery, reduces morbidity and
      shortens hospital stay. It is unclear what the effects are of laparoscopic or
      open surgery within a fast track programme. The aim of this systematic review was
      to review the existing evidence. METHOD: A systematic review was performed of all
      randomized (RCTs) and controlled clinical trials (CCTs) on laparoscopic and open
      surgery within a fast track setting. Primary endpoints were primary and overall
      hospital stay, readmission rate, morbidity and mortality. Study selection,
      quality assessment and data extraction were performed independently by two
      observers. RESULTS: Only two RCTs and three CCTs were eligible for final
      analysis, which reported on 400 patients. Data could not be pooled because of
      clinical heterogeneity. One RCT and one CCT stated a shorter primary hospital
      stay in the laparoscopic group of 3 and 2 days, respectively. In one RCT, the
      readmission rate was lower in the laparoscopic group; absolute risk reduction
      (ARR) 21.4% [95% confidence interval (CI): 6-42.3%] resulting in a number needed
      to treat (NNT) of 4.7 patients (95% CI: 2.4-176). Another study showed a 23%
      difference in favour of the laparoscopic group with regard to morbidity (95% CI:
      6.3-39.1%), i.e. an NNT of 4.4 patients (95% CI: 2.6-15.9). There were no
      significant differences in mortality rates. CONCLUSION: Due to the present lack
      of data, no robust conclusions can be made. A large randomized controlled trial
      is required to compare laparoscopic with open surgery within a fast track
      setting.

PMID- 18727716
TI  - Self expanding wall stents in malignant colorectal cancer: is  complete
      obstruction a contraindication to stent placement?
AB  - OBJECTIVE: Technical failures have previously been associated with complete
      clinical obstruction and complete block to the retrograde flow of gastrograffin
      is considered by some to be a contraindication to the procedure. We report on the
      technical and clinical success rates of self-expanding metallic stents (SEMS) in
      both complete and incomplete obstruction in a prospective series of malignant
      colorectal obstructions. METHOD: A prospective study of all patients undergoing
      attempted palliative and bridge to surgery SEMS placement for malignant
      colorectal obstruction over a 7-year period (April 1999-October 2006) was
      undertaken. RESULTS: Seventy-two patients (49 males) with a mean age of 71 years
      (range 49-98) were included. Technical success was achieved in 27 of 32 patients
      (84%) with complete obstruction and 33 of 36 patients (92%) with incomplete
      obstruction, P < 0.46, Fishers exact test. Clinical success was achieved in 17 of
      26 patients (65%) with complete obstruction and 24 of 33 patients (73%) with
      incomplete obstruction, P < 0.58, Fishers exact test. Although placed correctly
      in 89% cases, relief of symptoms occurred in only 71%, P = 0.002, matched pairs
      test. There were two colonic perforations in the series with one procedure
      related death. CONCLUSION: Placement of SEMS for obstructing colorectal cancer is
      technically successful in a high proportion of cases. Complete radiological
      obstruction is not a contraindication to stent placement. The relief of
      obstructive symptoms following successful placement of a wall stent is less
      predictable.

PMID- 18727717
TI  - Endoscopic transanal resection of rectal adenomas using the  urological
      resectoscope.
AB  - OBJECTIVE: Large sessile rectal adenomas are often difficult to excise and
      several different techniques have been described. This study evaluates the
      results of adenoma excision by endoscopic transanal resection using the
      urological resectoscope by a single surgeon in a UK district general hospital.
      METHOD: Between January 1989 and November 2004, data on all patients treated by
      endoscopic transanal resection of benign rectal tumours using a urological
      resectoscope (ETAR) were prospectively collected and analysed. RESULTS: Forty
      patients (50% male, median age 72 years) underwent a total of 81 endoscopic
      transanal resections. The tumour characteristics were: size > 2 cm (83%),
      location in lower 2/3 of rectum (83%) and extensive circumferential carpet-like
      appearances (13%). Fifty percent of the patients required only one procedure to
      achieve clearance. Mean operative time was 26 min (range 10-65 min). Seventy
      eight percent of the patients were discharged home within 24 h. Postoperative
      morbidity was 8% and in-hospital mortality was zero. Histology revealed severe
      dysplasia in 48% of the tumours and five patients were incidentally found to have
      foci of rectal adenocarcinoma. With a median follow-up of 47 months (range 2-162
      months), local recurrences occurred in 13% (n = 5) of patients. All, except one,
      were treated successfully with further endoscopic transanal resections.
      CONCLUSION: ETAR is simple and safe for managing rectal adenomas.

PMID- 18727721
TI  - Sacral nerve stimulation for faecal incontinence: long-term outcome.
AB  - AIM: The efficacy of sacral nerve stimulation (SNS) to treat faecal incontinence
      has been demonstrated in the short- and mid-term. We analysed SNS outcome in the
      first patients with a permanent neurostimulator in whom follow-up ranges up to 14
      years. METHOD: Of 12 patients who underwent SNS from 1994 to 1999, 9 were
      eligible for long-term analysis (defined as a minimum of 7 years). In 3 the
      device had to be removed because of pain or neurological disease. Functional
      outcome was monitored prospectively by standardized questionnaire. For efficacy,
      the recorded frequency of incontinent episodes over 2-week periods and the Wexner
      Score were obtained yearly after implant. Quality of life measures (FIQL scale
      [QoL]) were introduced in 1998. Stimulation parameter adjustments, battery
      longevity, and complications were documented. RESULTS: Mean follow-up in the nine
      patients was 9.8 years (range 7-14), over which time efficacy persisted. Clinical
      improvement was significant (baseline vs last follow-up): median percentage of
      incontinent bowel movements/week 40% (range 9-100) vs 0% (0-60%; P = 0.008),
      median number of incontinent episodes/week, 9 (range 2-58) vs 0 (0-29; P =
      0.012); median Cleveland Clinic Score, 17 (range 12-19) vs 10 (3-14; P < 0.007);
      QoL improved in all categories. Pulse generator exchange was required in eight of
      the nine patients after a mean of 7.4 years for battery fatigue (mean 2.1 V).
      Complications occurred in five of the original 12 and were therapy-related, but
      not technique-related, in four patients. CONCLUSION: Sacral nerve stimulation is
      an effective and safe long-term treatment for faecal incontinence. Clinical
      outcome is stable over time.

PMID- 18727725
TI  - A unique case of Hajdu-Cheney syndrome and squamous cell carcinoma of the anus.
AB  - OBJECTIVE: Hajdu-Cheney syndrome (HCS), first described in 1948 by Hajdu and
      independently in 1965 by Cheney, is an extremely rare disorder characterized by
      severe and excessive bone resorption leading to osteoporosis, with a wide range
      of other systemic complications from connective tissue and bone dysplasia.
      Currently there are approximately 50 distinct cases reported in the literature.
      There have been several reports associating polycystic kidneys with HCS and
      several other connective tissue disorders, suggesting a possibility of a
      hyperproliferative component to the syndrome. No articles exist in the current
      literature describing a case of HCS with concurrent carcinoma. Here, we present a
      case of a 54-year-old nonimmune compromised woman with multiple stigmata of HCS
      and recently diagnosed anal squamous cell carcinoma. METHOD: This is a case
      report of HCS and stage T3N0 squamous cell carcinoma of the anus. RESULTS: This
      is the first report of a patient with HCS with malignancy. CONCLUSIONS: We
      present a patient with HCS who developed anal squamous cell carcinoma. The
      mechanism of HCS, which is still unknown, may either make patients more
      susceptible to carcinoma or may just be a reflection of the normal incidence of
      anal squamous cell carcinoma given attributable risk factors.

PMID- 18727727
TI  - Restoration of bowel continuity after surgery for acute perforated
      diverticulitis: should Hartmann's procedure be considered a one-stage procedure?
AB  - OBJECTIVE: Hartmann's procedure (HP) still remains the most frequently performed
      procedure in acute perforated diverticulitis, but it results in a end colostomy.
      Primary anastomosis (PA) with or without defunctioning loop ileostomy (DI) seems
      a good alternative. The aim of this study was to assess differences in the rate
      of stomal reversal after HP and PA with DI and to evaluate factors associated
      with postreversal morbidity in patients operated for acute perforated
      diverticulitis. METHOD: All 158 patients who had survived emergency surgery for
      acute perforated diverticulitis in five teaching hospitals in The Netherlands
      between 1995 and 2005 and underwent HP or PA with DI were retrospectively
      studied. Age, gender, ASA-classification, severity of primary disease, delay of
      stoma reversal, surgeon's experience, surgical procedure and type of anastomosis
      were analysed in relation to outcome after stoma reversal. RESULTS: Of the 158
      patients, 139 had undergone HP and 19 PA with DI. The reversal-rate was higher in
      patients with DI (14/19; 74%) compared to HP (63/139; 45%) (P = 0.027) Delay
      between primary surgery and stoma reversal was shorter after PA with DI compared
      with HP (3.9 vs 9.1 months; P < 0.001). Cumulative postreversal morbidity after
      HP was 44%. Early surgical complications occurred in 22 of 63 patients. Morbidity
      after DI reversal was 15% (P < 0.001). Three patients died after HP reversal,
      none died after DI reversal. Anastomotic leakage was observed in 10 patients
      after HP reversal. This was less frequently observed when the operation was
      performed by a specialist colorectal surgeon (10%vs 33%; P = 0.049) and when a
      stapled anastomosis was performed (4%vs 24%; P = 0.037). CONCLUSIONS: Reversal of
      HP should only be performed by an experienced colorectal surgeon, preferably
      performing a stapled anastomosis, or probably not be performed at all, as it is
      accompanied by high postoperative morbidity and even mortality. It is important
      that these findings are taken in account for when performing primary emergency
      surgery for acute perforated diverticulitis.

PMID- 18727729
TI  - Spermiogenesis defects in human: detection of transition proteins in semen from
      some infertile men.
AB  - Semen samples from 60 infertile men were examined by flow cytometry following
      propidium iodide staining. Of these, 23 samples contained young haploid cells.
      Transition proteins (TP1 and/or TP2) were detected in 12 of these, using
      immunohistochemical staining. The presence of TPs in spermatids in semen
      indicates inhibition in the differentiation pathway from round spermatids to
      spermatozoa. Cells of this type were found in semen from patients with
      nonobstructive azoospermia, severe to extreme cases of oligozoospermia,
      asthenozoospermia and teratozoospermia.

PMID- 18727730
TI  - Screening for bacterial pathogens in semen samples from infertile men with and
      without leukocytospermia.
AB  - We aimed to study the correlation between leukocyte counts in semen and bacterial
      pathogens in seminal samples of infertile men, and to establish the minimum
      leukocyte count associated with significant bacteriospermia. A total of 116
      patients who underwent evaluation of fertility were investigated using routine
      semen analysis according to the guidelines of the WHO and bacterial pathogens
      analysis by culture and in-house PCR assay. The overall prevalence of
      bacteriospermia in semen samples was 56.9% independent of the presence of
      leukocytes. The most common bacterial species detected were Chlamydia trachomatis
      (41.4%), Ureaplasma urealyticum (15.5%) and Mycoplasma hominis (10.3%). The
      receiver operating characteristic curve analysis demonstrated that the
      sensitivity/specificity for detecting bacteria at a cut off level of >or=1 x
      10(6) leukocytes per ml (which is the WHO defined level for leukocytospermia) was
      20.3%/81.5%. The highest sensitivity/specificity ratio was found in semen samples
      with a cut-off level of >or=0.275 x 10(6) leukocytes per ml, which is best shown
      with the odds ratio of 2.47. A significant correlation was found between
      bacteriospermia and leukocytospermia at the cut-off level of >or=0.275 x 10(6)
      leukocytes per ml of semen samples (P = 0.032). We proposed that this is a
      possible new cut-off level to predict the presence of bacteria in semen of
      infertile men.

PMID- 18727731
TI  - Microdissection testicular sperm extraction and IVF-ICSI outcome in
      nonobstructive azoospermia.
AB  - We evaluated the efficiency of microdissection testicular sperm extraction
      (MicroTESE) in patients with nonobstructive azoospermia (NOA) and their pregnancy
      outcomes in a programme based on in vitro fertilisation (IVF)/intracytoplasmic
      sperm injection (ICSI). Fifty-six MicroTESE procedures were performed in 53
      patients with NOA. Pre-operative levels of luteinising hormone, follicle
      stimulating hormone (FSH), testosterone and prolactin were obtained and a Doppler
      sonography examination was conducted. Sperm retrieval rate, mean age of female
      partner, mean ICSI and fertilisation rate, number and quality of embryos
      transferred, implantation, pregnancy and miscarriage rates were calculated.
      Samples for testicular histological analysis were taken trans-operatively in
      every case. Sperm retrieval rate, mean ICSI per case and fertilisation rate were
      57.1%, 7.4% and 58.4% respectively. A significant difference in pre-operative
      testicular volume (P = 0.001), serum FSH (P = 0.008) and total testosterone
      levels (P = 0.021) was found in patients from whom sperm could be retrieved. Mean
      1.9 type A embryos were transferred per cycle. Implantation, clinical pregnancy
      and miscarriage rates were 20%, 40% and 18.7% respectively. It is concluded that
      MicroTESE is a viable option for men with NOA, offering excellent results in
      couples undergoing IVF-ICSI. Pre-operative serum FSH, testicular volume and total
      testosterone levels may have a prognostic value, although more data are needed to
      determine their significance and whether or not patients should be excluded from
      an initial sperm retrieval attempt.

PMID- 18727732
TI  - Antisperm antibodies detected by mixed agglutination reaction and immunobead test
      are not associated with chronic inflammation and infection of the seminal tract.
AB  - The association between chronic inflammatory/infectious diseases of the male
      reproductive tract and the presence of antisperm antibodies (ASA) in semen is
      still controversial. We compared the results of the mixed agglutinin reaction
      (MAR) test and immunobead test for detecting ASA type IgG and IgA in 133 patients
      attending our special outpatient department for andrological infections and
      evaluated the differences in the detection rate of ASA. Patients were divided
      into three groups: a study group that included 79 patients with symptomatic
      nonacute inflammatory/infectious diseases of the seminal tract, a control group
      (n = 44) and a third group of men with a history of successful vasectomy reversal
      (n = 10). The two tests correlated in a statistically significant manner for the
      detection of IgG and IgA in all groups. The overall positive detection rate of
      clinical significant levels of IgG and IgA was 2.5% and 1.3% (respectively) in
      the patients with inflammation/infection of the seminal tract. No statistical
      significant difference in the detection rate of ASA levels between the
      inflammatory/infectious group and the controls was detected. The results of the
      MAR test and immunobead test have a statistical significant correlation and their
      results provide evidence that there is no association between
      inflammatory/infectious diseases of the male reproductive tract and the presence
      of ASA in semen.

PMID- 18727733
TI  - Blocking E-selectin inhibits ischaemia-reperfusion-induced neutrophil recruitment
      to the murine testis.
AB  - Germ cell-specific apoptosis that occurs after ischaemia-reperfusion (IR) of the
      murine testis is dependent on neutrophil recruitment to the testis and is
      dependent upon the cell adhesion molecule E-selectin. In this study, we aimed to
      inhibit neutrophil recruitment to the IR-induced testis. Mice were subjected to a
      2-h period of testicular torsion (ischaemia) followed by detorsion (reperfusion).
      Shortly after onset of reperfusion, mice received either a function-blocking
      monoclonal anti-mouse E-selectin antibody (FBmAb) or isotype-matched control
      antibody. Mice were killed 24 h after reperfusion and cells isolated from the
      testis were analysed for the presence of neutrophil infiltration by flow
      cytometry. Administration of FBmAb inhibited neutrophil recruitment to the IR
      induced testis dramatically. Therefore, blockage of E-selectin may be a strategy
      to treat post-ischaemic testis.

PMID- 18727734
TI  - Hyperprolactinaemia due to hypothalamic-pituitary disease or drug-induced in
      patients with erectile dysfunction.
AB  - One hundred and sixty-five patients with erectile dysfunction were assessed at
      the Athens Medical Sex Institute: 60 men (36.4%) considered their condition as
      organic, 52 (31.5%) rated it as mostly psychogenic, 45 (27.2%) thought it could
      be of mixed aetiology and 8 (4.8%) could not comment at all as to the aetiology.
      Initial psychologic evaluation rated the condition in the majority of cases as
      psychogenic (130 patients, 84.8%). No psychologist considered the erectile
      dysfunction as purely (100%) organic. After the urological and endocrine
      evaluation, vascular disorder was considered in 30 patients (18.2%), endocrine
      dysfunction in 16 patients (9.7%) and psychogenic in 109 patients (66.1%).
      Sixteen of the above patients had definite hyperprolactinaemia, two had large
      sized prolactinomas as revealed by magnetic resonance imaging (MRI) and pituitary
      function tests. Four had nonfunctioning pituitary tumours, which was also based
      on MRI and pituitary tests. Four had small prolactin (PRL) adenomas. Drug-induced
      hyperprolactinaemia was suspected in six patients who used medications affecting
      PRL secretion and had no evidence of tumour on radiological evaluation. In
      conclusion, hyperprolactinaemia in men with erectile dysfunction needs to be
      evaluated before considering any other treatment.

PMID- 18727735
TI  - Effect of varicocele on chromatin condensation and DNA integrity of ejaculated
      spermatozoa using cytochemical tests.
AB  - Varicocele occurs in approximately 15% to 20% of the general male population and
      it is the most common cause of poor semen production and decreased semen quality.
      It has been demonstrated that patients with varicocele have a significantly
      higher DNA fragmentation index (DFI) and spermatozoa with nuclear anomalies than
      healthy fertile men. Therefore, the aim of this study was to evaluate sperm
      chromatin integrity in these patients. Sixty men referring to the andrology
      laboratory were categorised into three different groups: 20 infertile men with
      varicocele, 20 infertile men with abnormal semen parameters and 20 fertile men
      who had normal spermatogram were considered as control group. Semen analysis was
      performed according to WHO criteria. To evaluate sperm chromatin quality and DNA
      integrity, after fixation of sperm smears, aniline blue, toluidine blue,
      chromomycin A(3) and acridine orange staining were applied in three groups. The
      slides were analysed by light and fluorescent microscopy and to determine the
      percentage of mature or immature spermatozoa, 200 spermatozoa were counted in
      each slide. The results showed that the rates of aniline blue-reacted spermatozoa
      were significantly higher in infertile and varicocele patients than in the normal
      group (P < 0.001). In addition, with regard to chromomycin A(3), acridine orange
      and toluidine blue staining, there was a significant difference between the three
      groups (P < 0.001). The results showed that the varicocele samples contain a
      higher proportion of spermatozoa with abnormal DNA and immature chromatin than
      those from fertile men as well as infertile men without varicocele. Therefore,
      varicocele results in the production of spermatozoa with less condensed chromatin
      and this is one of the possible causes of infertility due to varicocele.

PMID- 18727736
TI  - Expression and putative function of lymphocyte endothelial epithelial-cell
      adhesion molecule in human testis.
AB  - The testis is an immunologically privileged site where germ cell antigens are
      protected from autoimmune attack and foreign tissue grafts may survive for
      extended periods. However, the testicular environment does not preclude
      inflammatory reactions and tissue-specific recruitment of T lymphocytes appears
      to be a crucial component of the inflammation cascade. Here, we demonstrate
      expression of lymphocyte endothelial epithelial-cell adhesion molecule (LEEP
      CAM), a putative receptor mediating lymphocyte adhesion to endothelia and some
      epithelia, in human testis. In all specimens examined, expression of LEEP-CAM
      could be observed on endothelial cells of testicular blood vessels, including
      those within the lamina propria of seminiferous tubules. Sections of
      histologically normal testis showed strong LEEP-CAM expression within the
      seminiferous epithelium localised to Sertoli cells, whereas immunoreactivity was
      almost absent in tubules with severely impaired spermatogenesis. In a modified
      Stamper-Woodruff adhesion assay, binding of activated lymphocytes to normal
      testicular tissue was reduced by 61% after incubation with anti-LEEP-CAM mAb as
      compared with controls (P < 0.00001). In conclusion, intratubular LEEP-CAM
      expression is correlated with normal spermatogenesis and Sertoli cell function.
      In this context, it may contribute to adhesive cell-cell interactions. Moreover,
      the constitutive expression in human testis could play a role for localisation of
      T cells during testicular inflammation.

PMID- 18727737
TI  - Metabolic syndrome, testosterone deficiency and erectile dysfunction never come
      alone.
AB  - Until a decade ago the ailments of elderly men, such as atherosclerosis,
      hypertension, diabetes mellitus, lower urinary tract symptoms and erectile
      dysfunction (ED), were regarded as distinct diagnostic/therapeutic entities but
      there is a growing awareness that these entities are not disparate and, to
      improve the health of the ageing male, require an integral approach. There is an
      inter-dependence between the metabolic syndrome, ED and patterns of testosterone
      in ageing men. The main features of the metabolic syndrome are abdominal obesity,
      insulin resistance, hypertension and dyslipidaemia, significant factors in the
      aetiology of erectile function. The metabolic syndrome is associated with lower
      than-normal testosterone levels. A new concept of the role of testosterone in
      male physiology suggests that testosterone plays also a significant role in the
      development and maintenance of bone and muscle mass and is a determinant of
      glucose homeostasis and lipid metabolism. Testosterone is not only a factor in
      libido but exerts also essential effects on the anatomical and physiological
      substrate of penile erection. With these recent insights, the health problems of
      elderly men must be placed in a context that allows an integral approach.
      Treatment of testosterone deficiency is to become part and parcel of this
      approach.

PMID- 18727738
TI  - Triorchidism: a case report and review of similar conditions.
AB  - Polyorchidism is a rare anomaly, defined as the presence of more than two
      testicles with about 100 cases reported in the literature. The majority of cases
      were triorchidism with occasional bilateral duplication. We report the case of a
      32-year-old man with polyorchidism, presenting with primary infertility with
      oligoasthenoteratozoospermia semen profile. Scrotal examination revealed two
      discrete ovoid nontender, firm, mobile lumps with testicular sensation in the
      right side of the scrotum. Ultrasonography and magnetic resonance imaging
      confirmed the presence of double testes with double separate epididymides sharing
      a common vas deferens in the right side of the scrotum. It demonstrated similar
      echo texture and vascular flow in both right-sided testicles although smaller in
      size than the left testis. The case was managed conservatively without surgical
      intervention with follow-up. Tracing of similar conditions in the literature was
      discussed.

PMID- 18727740
TI  - Analysis and reporting of clinical trials.

PMID- 18727741
TI  - ITT in respect to GCP: a matter of diligence.

PMID- 18727742
TI  - Intention-to-treat has implications for study planning and execution, not just
      subject retention and follow-up.

PMID- 18727743
TI  - Advancing development of nursing theory: an innovative approach.

PMID- 18727744
TI  - Massage for symptom relief in patients with cancer: systematic review.
AB  - AIM: This paper is a report of a review to assess evidence of the effectiveness
      of massage for patients with cancer, in terms of reducing physical or
      psychological symptoms, improving quality of life, or producing unwanted side
      effects. BACKGROUND: Patients with cancer may use complementary therapies,
      including massage and aromatherapy massage. However, their use and provision by
      state-financed healthcare services is controversial. DATA SOURCES: A systematic
      review was carried out, using the Cochrane principles. No meta-analysis was
      appropriate. An initial comprehensive search of electronic databases search was
      carried out in 2003 and updated in 2006. Eligible trials were randomized
      controlled trials, controlled before-and-after (pre-post) studies and interrupted
      time-series studies. Participants were adults with a diagnosis of cancer and
      receiving care in any healthcare setting. Interventions were limited to massage
      and/or aromatherapy massage carried out by a qualified therapist. Outcome
      measures to be included were patient-reported levels of physical and
      psychological indices of symptom distress and quality of life (measured using
      validated assessment tools). FINDINGS: In the review, 1325 papers were
      considered. Ten trials met the inclusion criteria and their results suggest that
      massage might reduce anxiety in patients with cancer in the short term and may
      have a beneficial effect on physical symptoms of cancer, such as pain and nausea.
      However, the lack of rigorous research evidence precludes drawing definitive
      conclusions. CONCLUSION: Further well-designed large trials with longer follow-up
      periods are needed to be able to draw firm conclusions about the efficacy and
      effectiveness of massage for cancer patients.

PMID- 18727745
TI  - Hygiene interventions for prevention of cytomegalovirus infection among
      childbearing women: systematic review.
AB  - AIM: This paper is a report of a systematic review to examine the effectiveness
      of preventive interventions to reduce congenital cytomegalovirus transmission and
      infection among women of childbearing age. BACKGROUND: Congenital cytomegalovirus
      has been identified as the leading infectious cause of damage to the growing
      fetus in developed countries, including Down syndrome, fetal alcohol syndrome and
      spina bifida. Despite the prevalence and consequences of this infection, it has a
      low profile and pregnant mothers are often unaware of the risks and protective
      behaviours related to its transmission. Women with children in daycare and nurses
      working with children are particularly at risk of acquiring the virus. DATA
      SOURCES: A computerized literature search for articles up to 1 December 2007 was
      performed using MEDLINE (from 1950); EMBASE (from 1980) and CINAHL (from 1982).
      REVIEW METHODS: Both authors independently reviewed studies that met inclusion
      criteria and assigned a quality rating determined by the number of validity
      criteria met. Differences were discussed until consensus was reached. FINDINGS:
      Differences in hygiene behaviour changes were most statistically significant for
      pregnant, seronegative women. Although the methodological quality of the three
      included studies was not strong, seroconversion rates consistently decreased as
      cytomegalovirus education and support increased. CONCLUSION: Nurses can act as
      preventive agents for cytomegalovirus infection through education about hygiene
      precautions during antenatal care and through preventive measures in the
      workplace. The review findings suggest educational interventions in hygiene
      practices have the potential to be a feasible, large-scale, primary prevention
      strategy.

PMID- 18727748
TI  - Experiencing cancer treatment decision-making in managed care.
AB  - AIM: This paper is a report of a study to explore women's perceptions of and
      experiences with breast cancer treatment decision-making in managed care
      organizations (MCOs). BACKGROUND: Managed care organizations are the predominant
      form of employer-sponsored healthcare insurance in the United States of America.
      These healthcare financing entities minimize cost by streamlining healthcare
      delivery and may impose choice restrictions. The extent of these restrictions has
      not previously been studied from an in-depth patient perspective. METHOD: A
      qualitative descriptive approach was adopted using interviews with a purposive
      sample of 14 managed care enrollees diagnosed with breast cancer at all stages.
      The data were collected between 2003 and 2005. Data analysis involved a reflexive
      process of transcript reading, categorization, data reduction and interpretation.
      FINDINGS: The findings are presented as a single theme: 'decisional conflict in
      managed care', with two distinct categories: decisions regarding (1) the MCOs and
      (2) treatment. MCO selection was perceived to be limited by employer constraints,
      cost issues or healthcare plan providers. For study participants, selecting a MCO
      was less difficult than issues surrounding treatment decision-making. Women
      reported that their most important treatment-related decisions surrounded
      diagnosis and involved selecting a treatment facility and provider. Once a
      satisfactory facility and provider were selected, these women preferred to defer
      treatment decisions to their healthcare providers. CONCLUSION: Decision
      interventions should be focused on assisting women with provider and treatment
      facility selection early in diagnosis. Our findings might also serve as a basis
      for policy/practice changes to address healthcare financing limitations and to
      expand cancer treatment-related choices while providing desired treatment
      decision-making support.

PMID- 18727749
TI  - The importance of transformational leadership style for the well-being of
      employees working with older people.
AB  - AIM: This paper is a report of a study to explore the relationships between
      transformational leadership, followers' perceived working conditions and employee
      well-being and job satisfaction. BACKGROUND: There is some evidence that
      transformational leadership style is linked to employee job satisfaction and well
      being. However, it is not clear whether this is due to (i) a direct relationship
      between leadership and job satisfaction and well-being outcomes or (ii) whether
      followers' perceived working conditions mediate this relationship. METHODS: A
      cross-sectional design was applied to data from a questionnaire study of 447
      staff caring for older people in Denmark. Data were collected in 2005. A theory
      driven model of the relationships between leadership, working conditions, job
      satisfaction and well-being was tested using structural equation modelling.
      RESULTS: The transformational leadership style was closely associated with
      followers' working conditions, namely involvement, influence and meaningfulness.
      Involvement was associated with job satisfaction and meaningfulness was
      associated with well-being. However, working conditions were closely correlated
      with each other, and thus the mediating mechanisms may operate through several
      different working conditions. A direct path between leadership behaviour and
      employee well-being was also found. CONCLUSION: Considering working conditions in
      the absence of studying leadership behaviour (or vice versa) may reveal an
      incomplete picture of the impact of work and work relationships on well-being.
      Work re-design interventions focused on influence may benefit from the
      consideration of training managers to exert transformational leadership
      behaviours.

PMID- 18727750
TI  - Postoperative pain and self-management: women's experiences after cardiac
      surgery.
AB  - AIM: This paper is a report of a study to describe women's experiences and their
      self-management of postoperative pain after elective cardiac surgery. BACKGROUND:
      Cardiac surgery involves several pain-sensitive areas, and untreated
      postoperative pain may lead to chronic pain. Early discharge requires increased
      patient participation in pain management. Women report more postoperative pain
      than men after cardiac surgery. METHODS: Semi-structured interviews were
      conducted in 2004-2005 with 10 women 1-2 weeks after discharge from their first
      elective cardiac surgery. Qualitative content analysis was used to identify
      recurring themes. Pain diaries were used to record postoperative pain experiences
      1-2 weeks before the interviews, providing more nuances to the experiences of
      pain and pain management. FINDINGS: Postoperative pain experiences varied from no
      pain to pain all the time. Worst pain intensity was recorded as moderate or more.
      Pain experiences depended on what women's expectations of pain after cardiac
      surgery. None wanted to complain about their painful experiences. The women had
      needed for more individualized information about self-management of pain, and had
      difficulties remembering the information they had received. Most did not want to
      use pain medication, or waited to do so until pain was unbearable. CONCLUSION:
      Patients need more individualized and gender-specific information before early
      discharge from cardiac surgery to improve self-management. More specific
      predischarge education on self-management using analgesics regularly might
      prevent pain ratings rising to a severe level after discharge home.

PMID- 18727751
TI  - Social selection and professional regulation for Master's degrees for nurses.
AB  - AIM: This paper is a report of a study to understand the perspectives of two sets
      of stakeholders, namely clinical nursing providers and nursing academics, on how
      registered nurses should be selected for Master's degree programmes. BACKGROUND:
      The proliferation of taught Master's programmes has led to concerns about a
      lowering of standards. Even with the expansion of professional Master's
      programmes, they remain one of the least researched areas of higher education.
      METHOD: The sampling strategy was a combination of convenience and snowball
      sampling. In-depth interviews were conducted in 2006-07 with 15 stakeholders and
      data were subjected to thematic content analysis. FINDINGS: There were
      differences in service providers' and academics' perceptions of access to
      Master's level education for nurses. Service providers engaged in regulatory
      practices, as evidenced in the way in which potential candidates were judged to
      be suitable or not to undertake a Master's-level education. Academic
      participants, in contrast, tended to have far fewer concerns about the career
      plans of applicants and were more likely to invoke discourses of academic
      educational admission practices. CONCLUSION: The health services need highly
      skilled, educated workers whose abilities and knowledge make an impact on the
      provision of effective patient and client care. This level of education can be
      achieved through continuing education of the professions by taught Master's
      degrees. It is imperative that an effective partnerships between clinical service
      providers and academics are developed to promote understanding of their
      respective perceptions of admission to the degree.

PMID- 18727752
TI  - Improving district nurses' confidence and knowledge in the principles and
      practice of palliative care.
AB  - AIM: This paper is a report of part of an evaluation of the impact of a national
      palliative care education and support programme on the knowledge and confidence
      of members of district nursing teams. BACKGROUND: District nursing teams are the
      mainstay of 'hands on' provision of care at home. In recognition of their central
      role, the English Department of Health commissioned a national palliative care
      education programme as postregistration education had been limited. METHODS: The
      evaluation, conducted between 2002 and 2004, had a mixed methods design. In the
      summative component, 1280 nurses were randomly selected from eight cancer
      networks to receive postal questionnaires 1 year apart, before and after the
      educational intervention. Changes in scores were calculated and a multiple
      regression analysis undertaken to identify predictors of improvement in
      confidence in competence and knowledge. The formative component involved
      qualitative interviews with a sub-sample of 39 district nurses participating in
      the programme. FINDINGS: Nurses who responded in both years (374/32%) were
      included in the analysis. There was a small statistically significant increase in
      confidence in palliative care competency and knowledge after participation in the
      educational programmes. Nurses without district nursing qualifications and who
      had never worked in specialist palliative care had the largest improvements in
      scores. Qualitative data supported these findings. CONCLUSION: The findings
      suggest that the education programme led to improvements in self-reported
      district nursing confidence in palliative care competencies and knowledge; it is
      likely that the baseline level of palliative care confidence in competency and
      knowledge has as a result been raised nationally.

PMID- 18727753
TI  - Reflecting peer-support groups in the prevention of stress and burnout:
      randomized controlled trial.
AB  - AIM: This paper is a report of a study to test the effect of participating in a
      reflecting peer-support group on self-reported health, burnout and on perceived
      changes in work conditions. BACKGROUND: Stress-related conditions are one of the
      most common causes for long-term sick-leave. There is limited evidence for the
      effectiveness of person-directed interventions aimed at reducing stress levels in
      healthcare workers. Prior research in the relationship between support and
      burnout show somewhat inconsistent results. METHOD: A randomized controlled trial
      with peer-support groups as the intervention was conducted with 660 healthcare
      workers scoring above the 75th percentile on the exhaustion dimension of the
      Oldenburg Burnout Inventory. One hundred and fifty-one (22.9%) agreed to
      participate. The intervention started in 2002 with 51 participants (96.1% were
      women), 80 of whom constituted the control group. Potential differences in
      outcome measures 12 months after the intervention were compared using ancova, and
      data collected was completed in 2004. Qualitative content analyses were used to
      analyse reported experiences from group participation. RESULTS: Statistically
      significant intervention effects were found for general health, perceived
      quantitative demands at work, participation and development opportunities at work
      and in support at work. Seven categories of experiences from participating were
      identified: talking to others in a similar situation, knowledge, sense of
      belonging, self-confidence, structure, relief of symptoms and behavioural change.
      CONCLUSION: Peer-support groups using a problem-based method could be a useful
      and comparatively inexpensive tool in alleviating work-related stress and
      burnout.

PMID- 18727755
TI  - In response to: Cantrell M. & Lupinacci P. (2007) Methodological issues in online
      data collection. Journal of Advanced Nursing60(5), 544-549.

PMID- 18727754
TI  - Experiences and challenges of informal caregiving for Korean immigrants.
AB  - AIM: This paper is a report of a study designed to explore the caregiving
      experiences of Korean Americans. BACKGROUND: Increasing numbers of older people
      in the Asian population place important long-term care demands on Asian
      caregivers, yet minimal attention has been given to the issue of caregiving in
      this group. The current study attempts to fill the gap by describing Korean
      American caregivers' unique caregiving experiences from their perspectives.
      METHOD: A qualitative research design using a focus group approach was employed
      to discuss caregiving experiences in a cultural context. Data were collected over
      an 8-month period in 2005. Twenty-four informants, mostly women, at varying
      points surrounding caregiving participated in a focus group interview. Each focus
      group lasted about 1 (1/2)-2 hours. Thematic analysis was conducted by two
      bilingual researchers. FINDINGS: Three key themes were identified: the caregiver
      role - competing priorities and beliefs, the extent and impact of caregiving, and
      the need for education and culturally-tailored support systems. Ten subthemes
      were identified within the three major themes: (1) facing double challenges; (2)
      changing attitudes about filial piety (Hyo); (3) providing care; (4) feeling out
      of control; (5) going through changing family dynamics; (6) being connected vs.
      providing connection; (7) paying back; (8) learning by themselves; (9)
      recognizing differences and (10) reconsidering geriatric care systems.
      CONCLUSION: The caregiving experiences described by Korean American families
      point to the need to identify and develop more focused outreach programmes as
      well as more culturally appropriate support services for this rapidly increasing
      population.

PMID- 18727757
TI  - AIDS and odds.

PMID- 18727758
TI  - Has the BARRIERS Scale changed nursing practice? An integrative review.
AB  - AIM: This paper is a report of a review to analyse studies using the BARRIERS
      Scale to determine (a) if the identification of perceived barriers to research
      utilization influences nurses' use of research, (b) if the extent of nurses'
      perceived barriers to research utilization and most frequently cited barriers
      have changed over the past 15 years and (c) if nurses' most frequently cited
      barriers to research utilization differ across countries. BACKGROUND: The
      BARRIERS Scale has been used to identify nurses' untoward perceptions or barriers
      to research utilization. DATA SOURCES: A computer search was conducted using the
      Cumulative Index of Nursing and Allied Health Literature, MEDLINE, Dissertation
      Abstracts International and Academic Abstracts to identify relevant literature
      from 1991 to 2006. The Internet and citations within studies were also searched.
      REVIEW METHODS: Studies were included if they were in English, used the entire
      BARRIERS Scale and reported nurses' responses. Studies were coded for author(s),
      publication year, country, population, sample size, response rate, the three-most
      frequently cited barriers, mean per cent of items rated as moderate or greater,
      and number of items identified as a barrier by 50% or more of respondents.
      Quality appraisal of the included papers was not performed. RESULTS: Forty-five
      studies met the inclusion criteria and predominantly identified the same
      barriers. No evidence was found that identification of barriers to nurses' use of
      research influenced nursing practice. CONCLUSIONS: It appears that there would be
      minimal benefit from further descriptive research using the BARRIERS Scale.
      Research is needed to investigate whether relationships exist between perceptions
      of barriers to nurses' use of research and the use evidence-based practice.

PMID- 18727759
TI  - Association between self-report pain ratings of child and parent, child and nurse
      and parent and nurse dyads: meta-analysis.
AB  - AIM: This paper is a report of a meta-analysis to investigate the association
      between self-report pain ratings for the dyads of child and parent, child and
      nurse and parent and nurse. BACKGROUND: Existing research has shown conflicting
      results with regard to agreements of self-report pain ratings between the three
      dyads. DATA SOURCES: The CINAHL, Medline, Ovid and PsycINFO databases were
      searched using keyword, such as 'children/adolescents', 'parents/nurses', 'pain
      assessment', 'pain ratings', 'association' and 'agreement'. Studies published in
      English in or after 1990 were included. METHODS: Meta-analysis methodology was
      applied to 12 pain assessment studies published between 1990 and 2007 which met
      the inclusion criteria. In the 12 studies a common effect size was estimated
      using the Pearson's correlation coefficient. Therefore, a fixed-effects model was
      chosen for this meta-analysis. RESULTS: We found moderate summary effect sizes
      between self-reported pain ratings for the dyad of child and parent (r = 0.64)
      and the child and nurse dyad (r = 0.58) and a weak summary effect size of r =
      0.49 for the dyad of parent and nurse. The summarized effect sizes for each of
      the three dyads varied across the studies. A test of homogeneity (Q-statistic)
      indicated that all effect size estimates were not homogeneous. CONCLUSION:
      Parents' and nurses' perceptions of children's pain should only be considered as
      estimates rather than expressions of the pain experienced, and not the same as
      children's self-reports. There is a need for education on selection of
      appropriate pain assessment scales in relation to the age and development of the
      child.

PMID- 18727762
TI  - Women's positions during the second stage of labour: views of primary care
      midwives.
AB  - AIM: This paper is a report of a study to explore the views of midwives on
      women's positions during the second stage of labour. BACKGROUND: Many authors
      recommend encouraging women to use positions that are most comfortable to them.
      Others advocate encouragement of non-supine positions, because offering 'choice'
      is not enough to reverse the strong cultural norm of giving birth in the supine
      position. Midwives' views on women's positions have rarely been explored. METHOD:
      Six focus groups were conducted in 2006-2007 with a purposive sample of 31
      midwives. The data were interpreted using Thachuk's models of informed consent
      and informed choice. FINDINGS: The models were useful in distinguishing between
      two different approaches of midwives to women's positions during labour. When
      giving informed consent, midwives implicitly or explicitly ask a woman's consent
      for what they themselves prefer. When offering informed choice, a woman's
      preference is the starting point, but midwives will suggest other options if this
      is in the woman's interest. Obstetric factors and working conditions are reasons
      to deviate from women's preferences. CONCLUSIONS: To give women an informed
      choice about birthing positions, midwives need to give them information during
      pregnancy and discuss their position preferences. Women should be prepared for
      the unpredictability of their feelings in labour and for obstetric factors that
      may interfere with their choice of position. Equipment for non-supine births
      should be more midwife-friendly. In addition, midwives and students need to be
      able to gain experience in assisting births in non-supine positions.

PMID- 18727763
TI  - Defying all odds: coping with the challenges of volunteer caregiving for patients
      with AIDS in South Africa.
AB  - AIM: This paper is a report of a study to explore the challenges experienced by
      volunteer caregivers of people living with HIV/AIDS and the strategies employed
      in coping with these challenges. BACKGROUND: Informal caregiving is associated
      with stresses that often results in poor health outcomes for caregivers. In South
      Africa, volunteers play a major role in the provision of care for people living
      with HIV/AIDS and have been shown to experience burdens as a result of caring.
      However, little is known about stress and coping among volunteer caregivers.
      METHODS: An ethnographic study was conducted, using observation and in-depth
      interviews, to collect data with 20 volunteers and other stakeholders in two semi
      rural communities in South Africa over a 19-month period in 2002/2003. FINDINGS:
      'Defying all odds' emerged as the central theme that encompassed the various ways
      in which volunteer caregivers dealt with the many practical challenges
      confronting them. These challenges initially posed a threat to volunteering work
      but were gradually appraised by volunteers as challenges that could be dealt with
      using various strategies in order to continue providing care. Eight themes
      highlighting these challenges and the coping strategies employed by volunteers
      were identified. CONCLUSION: A clear understanding of how volunteers deal with
      challenges of caring for people living with HIV/AIDS can give insight into their
      weaknesses and strengths and can inform the design of interventions aimed at
      providing support. Studies are needed to facilitate better understanding of the
      processes of appraisal of challenges by volunteers and the effectiveness of
      coping strategies, and to track coping strategies over time.

PMID- 18727764
TI  - Nursing recruitment: relationship between perceived employer image and nursing
      employees' recommendations.
AB  - AIM: This paper is a report of a study to examine the relationship between
      nursing employees' perceptions of instrumental and symbolic dimensions of
      employer image on the one hand and their intentions to recommend their
      organization as an employer and their willingness to testify in their
      organization's recruitment materials on the other. BACKGROUND: Previous research
      suggests that word-of-mouth recommendations by current nursing employees can
      enhance healthcare organizations' attractiveness as an employer for potential
      applicants. However, it is not known what motivates employees to provide positive
      word-of-mouth comments and to endorse their employer in recruitment testimonials.
      METHOD: The instrumental-symbolic framework was applied to identify relevant
      dimensions of perceived employer image that might relate to employee
      recommendations. A questionnaire was administered in 2006 to 106 nurses and
      nursing aides from four non-profit nursing homes in Belgium. The response rate
      was 55%. RESULTS: Overall, nursing employees were more willing to recommend their
      nursing home to others than to testify in recruitment materials. Both
      instrumental and symbolic employer image dimensions predicted nursing employees'
      recommendation intentions. Conversely, willingness to testify was only predicted
      by symbolic image dimensions. Specifically, the more the nursing employees
      perceived that their nursing home offers task diversity, offers the possibility
      to help people and is prestigious, the more they intended to recommend their
      organization to others. The more they perceived their nursing home as competent,
      the higher were their recommendation intentions and their willingness to testify
      in recruitment communication. CONCLUSION: To increase nursing employees'
      willingness to recommend their employer to potential applicants, organizations
      should enhance their perceived employer image.

PMID- 18727765
TI  - Parents' childhood fever management: community survey and instrument development.
AB  - AIM: This paper is a report of a study to explore Australian parents' knowledge,
      beliefs, practices and information sources about fever management and develop a
      scale to measure parents' fever management practices. BACKGROUND: Parental fever
      phobia and overuse of antipyretics to reduce fever continue. No scales to measure
      parents' fever management practices are available. METHOD: A community-based,
      postal survey was carried out in 2005 with 401 Australian parents of well
      children aged 6 months-5 years. Respondents were recruited through advertising
      (48.4%), face-to-face (26.4%) and snowball (24.4%) methods. A 33-item instrument
      was developed; construct and content validity were determined by an expert panel
      and item reliability by test-retest. RESULTS: Moderate fever (40.0 +/- 1.0
      degrees C) was reported to be harmful (88%), causing febrile convulsions (77.7%).
      Usual practices targeted temperature reduction, antipyretic administration
      (87.8%), temperature monitoring (52.5%). Fewer evidence-based practices, such as
      encouraging fluids (49.0%) and light clothing (43.8%), were reported. Positive
      changes over time (36.4%) included less concern and delayed or reduced
      antipyretic use. Negative practice changes (22.7%) included greater concern and
      increased antipyretic use. Medical advice was sought for illness symptoms (48.7%)
      and high (37.4%) or persistent (41.5%) fevers. Fever management was learnt from
      doctors, family and friends and working experience, while receiving conflicting
      information (41.9%) increased concerns and created uncertainty about best
      practice. CONCLUSION: Parents need consistent evidence-based information about
      childhood fever management. The Parental Fever Management Scale requires further
      testing with different populations and in different cultures and healthcare
      systems to evaluate its usefulness in nursing practice and research.

PMID- 18727766
TI  - Cultural encounters in reflective dialogue about nursing care: a qualitative
      study.
AB  - AIM: This paper is a report of a study to explore how students developed
      reflective nursing practice through cultural encounters between students from
      Tanzania and Norway. BACKGROUND: Nursing students need to develop cultural care
      competence to care for patients in a globalized world. One way to achieve this
      goal may be through international practice experience. Previous studies have
      shown that students visiting developing countries matured personally and
      intellectually more than those who experienced encounters between developed
      countries. METHOD: The study was exploratory, using qualitative data about
      nursing practice and cultural encounters experienced by nursing students from
      Tanzania and Norway. Data were collected through participatory observation,
      students' logs and focus group interviews in 2006. FINDINGS: The encounter was
      characterized with an open attitude facilitating a good context for co-learning
      between the students. Three main themes were identified. The Norwegian students
      emphasized nurse-patient relationships, individualized care, direct communication
      and emotional involvement. The Tanzanian nursing students demonstrated a
      collectivist approach in nursing characterized by nurse-relative-patient
      relationships, and they emphasized curing attributes with skillful performance of
      procedures. CONCLUSION: A cultural encounter between students from different
      culture proved to be a fruitful way of teaching nurses. The opportunity to share
      thoughts, reflect on value systems and personal practice through dialogue with
      students from a different culture offer possibility in terms of cultural
      competence, reflexivity and consciousness of various ways practising nursing.
      This may contribute to bringing the practice of nursing a step forward in both
      cultures.

PMID- 18727767
TI  - The influence of psychological factors on breastfeeding duration.
AB  - AIM: This paper reports on a study examining the relationship between women's
      psychological characteristics and breastfeeding duration, after controlling for
      socio-demographic factors. BACKGROUND: The literature suggests that psychological
      factors may influence breastfeeding behaviour, but studies are few. Existing
      evidence and the results of phase 1 of our study were used to construct a list of
      psychological factors, which were tested for their association with breastfeeding
      duration in the current design. METHOD: Participants were postnatal inpatients in
      one of two regional hospitals between October and December 2005 and they
      completed the initial questionnaire within 14 days of giving birth (n = 375).
      Infant feeding method at 6 months and the timing of introduction of other
      food(s), where relevant, were ascertained by telephone interview. FINDINGS: Forty
      four per cent of the sample showed signs of postnatal distress in the 14 days
      following the birth. Breastfeeding duration was statistically significantly
      associated with psychological factors including dispositional optimism,
      breastfeeding self-efficacy, faith in breastmilk, breastfeeding expectations,
      anxiety, planned duration of breastfeeding and the time of the infant feeding
      decision. As a set, these psychological factors were more predictive of
      breastfeeding duration than was the set of socio-demographic characteristics. The
      duration of any breastfeeding was uniquely predicted by faith in breastmilk,
      planned breastfeeding duration and breastfeeding self-efficacy. CONCLUSION: This
      increased knowledge of the factors influencing breastfeeding will assist in
      identifying women at risk of early weaning and in constructing programmes capable
      of increasing the length of time for which women breastfeed.

PMID- 18727768
TI  - Presence of patients' families during cardiopulmonary resuscitation: physicians'
      and nurses' opinions.
AB  - AIM: This paper is a report of a study to determine the opinions of physicians
      and nurses who work in a university hospital intensive care unit and emergency
      department about the presence of patients' families during cardiopulmonary
      resuscitation in these units. BACKGROUND: Healthcare professionals have
      conflicting opinions about the presence of patients' families during
      cardiopulmonary resuscitation. Families who are allowed to be present have less
      fear and worry, feel they have supported their family member and are able to cope
      more easily. METHOD: The data for this descriptive questionnaire study were
      collected between November 2006 and January 2007. The respondents were 62
      physicians and 82 nurses who worked in an emergency department or in cardiology
      or anaesthesia intensive care units in Turkey. The data were collected using a
      questionnaire and the responses summarized using frequencies and percentages. The
      chi-squared test was performed to test for differences in the opinion by
      profession, educational level, or number of years of working experience in the
      profession. FINDINGS: The response rate was 79%. Of the respondents, 82.6% did
      not think it was appropriate for patients' families to be present during
      cardiopulmonary resuscitation. The most common concerns mentioned were that the
      family would interfere with the team's activities (56.3%) and that resuscitation
      is a very traumatic procedure (43.6%). CONCLUSION: Policies need to be developed
      regarding this topic because the absence of policy can cause misunderstanding and
      differences in practice. Further research is needed to determine what public
      education is needed to facilitate implementation of such policies.

PMID- 18727769
TI  - Pain catastrophizing: a dimensional concept analysis.
AB  - AIM: This paper is a report of a concept analysis of pain catastrophizing.
      BACKGROUND: The importance of pain catastrophizing in the experience of pain and
      development of chronic pain has been demonstrated. It has been described as a
      tendency to have a fixation about pain and to feel unable to deal with pain. DATA
      SOURCES: Fifty-one papers containing the keyword 'pain catastrophizing' were
      selected from the Medline, Embase and Psycinfo indexes between 1996 and 2008.
      Dimensional analysis methodology was used to make explicit the ways in which the
      concept is constructed and used. The themes of this approach seem to contribute
      to the understanding of both nurse and client perspectives. RESULTS: The
      literature on 'pain catastrophizing' seems to reach a level of middle-range
      explanatory theory. The focus is on specifying relationships between pain
      catastrophizing and two or more concepts, and on validating the theoretical
      hypotheses of 'communal coping' as opposed to 'hypervigilance'. The predominance
      of correlational and cross-sectional studies testifies to this. The concept's
      definition includes the curative and preventive approaches. However, only the
      professional perspective seems to be reflected in the concept's terminology.
      CONCLUSION: Nursing theories and qualitative research seem to be avenues for the
      comprehension of the phenomenon and the broadening of perspectives. They may
      bring not only a new but also a unique perspective. Nevertheless, the current
      state of knowledge on pain catastrophizing is important to nurses as they could
      influence greatly the timing of interventions and prevention of chronic pain.

PMID- 18727770
TI  - Population structure of the parasitic nematode Anguillicola crassus, an invader
      of declining North Atlantic eel stocks.
AB  - Probably half of all animal species exhibit a parasitic lifestyle and numerous
      parasites have recently expanded their distribution and host ranges due to
      anthropogenic activities. Here, we report on the population genetic structure of
      the invasive nematode Anguillicola crassus, a parasite in freshwater eels, which
      recently spread from Asia to Europe and North America. Samples were collected
      from the newly colonized naive host species Anguilla anguilla (Europe) and
      Anguilla rostrata (North America), and from indigenous Anguilla japonica in
      Taiwan and Japan. Using seven microsatellite loci and one mitochondrial marker,
      we show that the parasite's population structure in Europe mirrors the
      zoogeographic Boreal-Lusitanian break along the English Channel. Both the north
      to-south decline of nuclear allelic diversity and the loss of private alleles in
      the same direction are consistent with a significant isolation-by-distance
      pattern based on rho(ST) values. In combination with the specific topology of the
      distance tree among nematode populations, our data suggest that Europe was
      invaded only once from Taiwan, and that subsequently, genetic diversity was lost
      due to random drift. On the contrary, the North American sample shares distinct
      nuclear and mitochondrial signatures with Japanese specimens. We propose that the
      genetic structure in Europe was shaped by long-range anthropogenic eel host
      transfers in the north and a single dispersal event into the southwest. The
      genetically distinct Brittany sample at the edge of the Boreal-Lusitanian
      boundary is indicative of natural dispersal of fish hosts since recruitment
      occurs naturally there and invertebrate host dissemination is interrupted due to
      oceanic currents.

PMID- 18727771
TI  - Chymopapain: a shot from the past.

PMID- 18727773
TI  - Sensory-specific satiety is intact in amnesics who eat multiple meals.
AB  - What is the relationship between memory and appetite? We explored this question
      by examining preferences for recently consumed food in patients with amnesia.
      Although the patients were unable to remember having eaten, and were inclined to
      eat multiple meals, we found that sensory-specific satiety was intact in these
      patients. The data suggest that sensory-specific satiety can occur in the absence
      of explicit memory for having eaten and that impaired sensory-specific satiety
      does not underlie the phenomenon of multiple-meal eating in amnesia. Overeating
      in amnesia may be due to disruption of learned control by physiological
      aftereffects of a recent meal or to problems utilizing internal cues relating to
      nutritional state.

PMID- 18727774
TI  - Recalibrating color categories using world knowledge.
AB  - When the perceptual system uses color to facilitate object recognition, it must
      solve the color-constancy problem: The light an object reflects to an observer's
      eyes confounds properties of the source of the illumination with the surface
      reflectance of the object. Information from the visual scene (bottom-up
      information) is insufficient to solve this problem. We show that observers use
      world knowledge about objects and their prototypical colors as a source of top
      down information to improve color constancy. Specifically, observers use world
      knowledge to recalibrate their color categories. Our results also suggest that
      similar effects previously observed in language perception are the consequence of
      a general perceptual process.

PMID- 18727775
TI  - Vision merges with touch in a purely tactile discrimination.
AB  - To construct a coherent percept of the world, the brain continuously combines
      information across multiple sensory modalities. Simple stimuli from different
      modalities are usually assumed to be processed in distinct brain areas. However,
      there is growing evidence that simultaneous stimulation of multiple modalities
      can influence the activity in unimodal sensory areas and improve or impair
      performance in unimodal tasks. Do these effects reflect a genuine cross-modal
      integration of sensory signals, or are they due to changes in the perceiver's
      ability to locate the stimulus in time and space? We used a behavioral measure to
      differentiate between these explanations. Our results demonstrate that, under
      certain circumstances, a noninformative flash of light can have facilitative or
      detrimental effects on a simple tactile discrimination. The effect of the visual
      flash mimics that produced by a constant tactile pedestal stimulus. These
      findings reveal that sensory signals from different modalities can be integrated,
      even for perceptual judgments within a single modality.

PMID- 18727776
TI  - Taking another person's perspective increases self-referential neural processing.

PMID- 18727777
TI  - Measuring the crowd within: probabilistic representations within individuals.

PMID- 18727778
TI  - The hidden-zero effect: representing a single choice as an extended sequence
      reduces impulsive choice.

PMID- 18727779
TI  - Are older adults less subject to the sunk-cost fallacy than younger adults?

PMID- 18727780
TI  - "Perceptual scotomas": a functional account of motion-induced blindness.
AB  - In motion-induced blindness (MIB), salient objects in full view can repeatedly
      fluctuate into and out of conscious awareness when superimposed onto certain
      global moving patterns. Here we suggest a new account of this striking
      phenomenon: Rather than being a failure of visual processing, MIB may be a
      functional product of the visual system's attempt to separate distal stimuli from
      artifacts of damage to the visual system itself. When a small object is invariant
      despite changes that are occurring to a global region of the surrounding visual
      field, the visual system may discount that stimulus as akin to a scotoma, and may
      thus expunge it from awareness. We describe three experiments demonstrating new
      phenomena predicted by this account and discuss how it can also explain several
      previous results.

PMID- 18727781
TI  - Figure-ground segmentation can occur without attention.
AB  - The question of whether or not figure-ground segmentation can occur without
      attention is unresolved. Early theorists assumed it can, but the evidence is
      scant and open to alternative interpretations. Recent research indicating that
      attention can influence figure-ground segmentation raises the question anew. We
      examined this issue by asking participants to perform a demanding change
      detection task on a small matrix presented on a task-irrelevant scene of
      alternating regions organized into figures and grounds by convexity.
      Independently of any change in the matrix, the figure-ground organization of the
      scene changed or remained the same. Changes in scene organization produced
      congruency effects on target-change judgments, even though, when probed with
      surprise questions, participants could report neither the figure-ground status of
      the region on which the matrix appeared nor any change in that status. When
      attending to the scene, participants reported figure-ground status and changes to
      it highly accurately. These results clearly demonstrate that figure-ground
      segmentation can occur without focal attention.

PMID- 18727782
TI  - If I'm not hot, are you hot or not? Physical attractiveness evaluations and
      dating preferences as a function of one's own attractiveness.
AB  - Prior research has established that people's own physical attractiveness affects
      their selection of romantic partners. This article provides further support for
      this effect and also examines a different, yet related, question: When less
      attractive people accept less attractive dates, do they persuade themselves that
      the people they choose to date are more physically attractive than others
      perceive them to be? Our analysis of data from the popular Web site
      http://HOTorNOT.com suggests that this is not the case: Less attractive people do
      not delude themselves into thinking that their dates are more physically
      attractive than others perceive them to be. Furthermore, the results also show
      that males, compared with females, are less affected by their own attractiveness
      when choosing whom to date.

PMID- 18727784
TI  - Objects on a collision path with the observer demand attention.
AB  - How observers distribute limited processing resources to regions of a scene is
      based on a dynamic balance between current goals and reflexive tendencies. Past
      research showed that these reflexive tendencies include orienting toward objects
      that expand as if they were looming toward the observer, presumably because this
      signal indicates an impending collision. Here we report that during visual
      search, items that loom abruptly capture attention more strongly when they
      approach from the periphery rather than from near the center of gaze (Experiment
      1), and target objects are more likely to be attended when they are on a
      collision path with the observer rather than on a near-miss path (Experiment 2).
      Both effects are exaggerated when search is performed in a large projection dome
      (Experiment 3). These findings suggest that the human visual system prioritizes
      events that are likely to require a behaviorally urgent response.

PMID- 18727783
TI  - Statistical learning using real-world scenes: extracting categorical regularities
      without conscious intent.
AB  - Recent work has shown that observers can parse streams of syllables, tones, or
      visual shapes and learn statistical regularities in them without conscious intent
      (e.g., learn that A is always followed by B). Here, we demonstrate that these
      statistical-learning mechanisms can operate at an abstract, conceptual level. In
      Experiments 1 and 2, observers incidentally learned which semantic categories of
      natural scenes covaried (e.g., kitchen scenes were always followed by forest
      scenes). In Experiments 3 and 4, category learning with images of scenes
      transferred to words that represented the categories. In each experiment, the
      category of the scenes was irrelevant to the task. Together, these results
      suggest that statistical-learning mechanisms can operate at a categorical level,
      enabling generalization of learned regularities using existing conceptual
      knowledge. Such mechanisms may guide learning in domains as disparate as the
      acquisition of causal knowledge and the development of cognitive maps from
      environmental exploration.

PMID- 18727785
TI  - Induced perceptual grouping.
AB  - The term perceptual grouping is associated with classical principles such as
      similarity and proximity. This article reports induced perceptual grouping, a
      phenomenon that occurs when placement of a uniform set of items near a structured
      set induces grouping within the otherwise uniform set. For example, when items
      grouped pair-wise by similarity are placed near another set of unstructured
      items, an analogous pair-wise grouping links elements of the second set. Induced
      grouping affected reaction times in two different visual search tasks, with
      reaction times depending on whether the target properties were contained within a
      group or crossed group boundaries as defined by induced grouping due to
      similarity, proximity, or common fate. Induced grouping was reduced when grouping
      between the structured and unstructured sets was weakened by means of a common
      region cue or decreased similarity. Induced grouping appears to reflect the
      computation of hierarchical structure in visual images.

PMID- 18727786
TI  - Error-monitoring ability predicts daily stress regulation.
AB  - This study examined whether individual differences in error-related self
      regulation predict emotion regulation in daily life, as suggested by a common
      systems view of cognitive and emotional self-regulation. Participants (N= 47)
      completed a Stroop task, from which error-related brain potentials and behavioral
      measures of error correction were computed. Participants subsequently reported on
      daily stressors and anxiety over a 2-week period. As predicted by the common
      systems view, a physiological marker of error monitoring and a behavioral measure
      of error correction predicted emotion regulation in daily life. Specifically,
      participants higher in cognitive control, as assessed neurally and behaviorally,
      were less reactive to stress in daily life. The results support the notion that
      cognitive control and emotion regulation depend on common or interacting systems.

PMID- 18727787
TI  - Sweet silent thought: alliteration and resonance in poetry comprehension.
AB  - Poetic devices like alliteration can heighten readers' aesthetic experiences and
      enhance poets' recall of their epic pieces. The effects of such devices on memory
      for and appreciation of poetry are well known; however, the mechanisms underlying
      these effects are not yet understood. We used current theories of language
      comprehension as a framework for understanding how alliteration affects
      comprehension processes. Across three experiments, alliterative cues reactivated
      readers' memories for previous information when it was phonologically similar to
      the cue. These effects were obtained when participants read aloud and when they
      read silently, and with poetry and prose. The results support everyday intuitions
      about the effects of poetry and aesthetics, and explain the nature of such
      effects. These findings extend the scope of general memory models by indicating
      their capacity to explain the influence of nonsemantic discourse features.

PMID- 18727788
TI  - Interracial roommate relationships: an experimental field test of the contact
      hypothesis.
AB  - This study investigated how automatically activated racial attitudes are affected
      by relatively long-term interracial relationships. A natural field experiment was
      conducted in a college dormitory system. Participants were White freshmen who had
      been randomly assigned to either a White or an African American roommate.
      Students participated in two sessions during the first 2 and last 2 weeks of
      their first quarter on campus. During these sessions, they answered questions
      about their satisfaction and involvement with their roommates and completed an
      inventory of intergroup anxiety and an implicit measure of racial attitudes.
      Participants in interracial rooms reported less satisfaction and less involvement
      with their roommates than did participants in same-race rooms. However,
      automatically activated racial attitudes and intergroup anxiety improved over
      time among students in interracial rooms, but not among students in same-race
      rooms. Thus, the results suggest that interracial roommate relationships,
      although generally less satisfying and involving than same-race roommate
      relationships, do produce benefits.

PMID- 18727789
TI  - Angry, disgusted, or afraid? Studies on the malleability of emotion perception.
AB  - Current theories of emotion perception posit that basic facial expressions signal
      categorically discrete emotions or affective dimensions of valence and arousal.
      In both cases, the information is thought to be directly "read out" from the face
      in a way that is largely immune to context. In contrast, the three studies
      reported here demonstrated that identical facial configurations convey strikingly
      different emotions and dimensional values depending on the affective context in
      which they are embedded. This effect is modulated by the similarity between the
      target facial expression and the facial expression typically associated with the
      context. Moreover, by monitoring eye movements, we demonstrated that
      characteristic fixation patterns previously thought to be determined solely by
      the facial expression are systematically modulated by emotional context already
      at very early stages of visual processing, even by the first time the face is
      fixated. Our results indicate that the perception of basic facial expressions is
      not context invariant and can be categorically altered by context at early
      perceptual levels.

PMID- 18727790
TI  - Effects of salience are short-lived.
AB  - A salient event in the visual field tends to attract attention and the eyes. To
      account for the effects of salience on visual selection, models generally assume
      that the human visual system continuously holds information concerning the
      relative salience of objects in the visual field. Here we show that salience in
      fact drives vision only during the short time interval immediately following the
      onset of a visual scene. In a saccadic target-selection task, human performance
      in making an eye movement to the most salient element in a display was accurate
      when response latencies were short, but was at chance when response latencies
      were long. In a manual discrimination task, performance in making a judgment of
      salience was more accurate with brief than with long display durations. These
      results suggest that salience is represented in the visual system only briefly
      after a visual image enters the brain.

PMID- 18727791
TI  - Why does writing about important values reduce defensiveness? Self-affirmation
      and the role of positive other-directed feelings.
AB  - Previous research has repeatedly shown that writing about an important value,
      compared with writing about an unimportant value, reduces defensiveness in
      response to self-threatening information, but has not identified why. Study 1
      showed that participants who wrote about an important value reported more
      positive other-directed feelings, such as love and connection, than participants
      who wrote about an unimportant value. Study 2 replicated this effect, and showed
      that loving and connected feelings, but not positive or negative self-directed
      feelings, completely accounted for the effect of a values-affirmation
      manipulation on smokers' acceptance of information indicating that smoking harms
      health. These studies, in concert with previous research, suggest that values
      affirmation reduces defensiveness via self-transcendence, rather than self
      integrity (i.e., self-worth or self-images).

PMID- 18727794
TI  - The association of early life exposure to antibiotics and the development of
      asthma, eczema and atopy in a birth cohort: confounding or causality?
AB  - BACKGROUND: In general, studies reporting positive associations between
      antibiotic exposure and respiratory and allergic disease have been unable to
      determine the nature of this association. OBJECTIVE: To examine the association
      between antibiotic exposure in infancy and the development of asthma, eczema and
      atopy in early childhood. METHODS: In a birth cohort study, we collected reported
      antibiotic exposure before 3 months and before 15 months along with outcomes
      (wheeze, asthma, eczema, rash, inhaler use) at 15 months (n=1011) and 4 years
      (n=986). Atopy was measured using skin prick tests at 15 months. RESULTS: We
      found significant univariate associations of antibiotic exposure before 3 months
      with asthma developing between birth and 15 months [OR 2.32 (95% CI 1.45-3.69)].
      After adjustment for chest infections, this association reduced (OR=1.58, 95% CI
      0.96-2.60) becoming marginally significant (P=0.07). A marginally significant
      association of antibiotics with atopy (OR=1.44, 95% CI 0.96-2.14) in the
      univariate analysis also reduced after adjustment for chest infections (OR=1.36,
      95% CI 0.91-2.05). There was no effect of antibiotic exposure before 15 months on
      asthma developing after 15 months and present between 3 and 4 years (OR=1.35 95%
      CI 0.85-2.14). Antibiotic exposure before 3 months was not associated with eczema
      and rash developing between birth and 15 months but exposure before 15 months was
      related to eczema [OR 1.83 (95% CI 1.10-3.05)] and rash [OR 1.61 (95% CI 1.02
      2.53)] developing after 15 months and remaining present at 4 years. These effects
      reduced in the multivariate analysis. CONCLUSIONS: Our findings suggest that the
      effect of antibiotics on respiratory disease may be due to confounding by chest
      infections at an early age when asthma may be indistinguishable from infection.

PMID- 18727797
TI  - Alternaria infections: laboratory diagnosis and relevant clinical features.
AB  - The genus Alternaria contains several species of melanized hyphomycetes that
      cause opportunistic human infections. The published literature contains 210
      reported cases of human alternarioses between 1933 and the present day. The most
      frequent clinical manifestations are cutaneous and subcutaneous infections
      (74.3%), followed by oculomycosis (9.5%), invasive and non-invasive
      rhinosinusitis (8.1%) and onychomycosis (8.1%). Immunosuppression is frequently
      associated with cutaneous and subcutaneous infections and rhinosinusitis. The
      most important risk factors for cutaneous and subcutaneous infections are solid
      organ transplantation and Cushing's syndrome, and those for rhinosinusitis are
      bone marrow transplants. Having been exposed to soil and garbage is common in all
      cases of oculomycosis, with corticotherapy being a risk factor in 50% of these
      cases. Previous contact with soil and/or trauma to the nails is associated with
      most cases of onychomycosis. In general, alternariosis shows a good response to
      conventional antifungal drugs. On some occasions, steroid suppression or
      reduction is sufficient to resolve an infection. Itraconazole is the antifungal
      drug used most frequently to successfully treat onychomycosis and cutaneous and
      subcutaneous infections. Posaconazole and voriconazole are promising therapeutic
      options, with the latter being especially so for oculomycosis.

PMID- 18727793
TI  - Immunoregulatory roles of eosinophils: a new look at a familiar cell.
AB  - Eosinophils are usually considered as end-stage degranulating effector cells of
      innate immunity. However, accumulating evidence has revealed additional roles for
      eosinophils that are immunoregulatory in nature in both the adaptive and innate
      arms of immunity. Specifically, eosinophils have key immunoregulatory roles as
      professional antigen-presenting cells and as modulators of CD4(+) T cell,
      dendritic cell, B cell, mast cell, neutrophil, and basophil functions. This
      review addresses the emerging immunoregulatory roles of eosinophils with a focus
      on recent data that support this new paradigm. Recognizing both the effector and
      immunoregulatory functions of eosinophils will enable a fuller understanding of
      the roles of eosinophils in allergic airways inflammation and may be pertinent to
      therapies that target eosinophils both for their acute and ongoing
      immunomodulatory functions.

PMID- 18727798
TI  - The dynamic relationship between antibiotic use and the incidence of vancomycin
      resistant Enterococcus: time-series modelling of 7-year surveillance data in a
      tertiary-care hospital.
AB  - The role of antibiotics in the epidemiology of vancomycin-resistant Enterococcus
      (VRE) has been studied extensively, but controversies remain as to which, and to
      what extent, antibiotics facilitate the emergence and dissemination of VRE in
      hospitals. Aggregate data on the use of several antibiotic classes in terms of
      defined daily doses (DDD) per 100 patient-days (PD), and VRE incidence rates in
      terms of clinical isolates per 1000 PD, were evaluated during a 7-year period at
      a tertiary-care hospital. Time-series analysis (autoregressive integrated moving
      average (ARIMA) and transfer function models) was used to quantify the temporal
      effect of antibiotic use on VRE incidence and estimate effect-delays. The
      incidence rate of VRE observed in a specific bimester was found to be a function
      of its value during the preceding bimester and of prior changes in the volume of
      use of four antibiotic classes. In particular, an increase of one DDD/100 PD in
      the use of glycopeptides, fluoroquinolones, extended-spectrum cephalosporins and
      beta-lactam-beta-lactamase inhibitor combinations resulted, independently, in
      average changes of +0.024, +0.015, + 0.020 and -0.010 isolates per 1000 PD in the
      incidence of VRE, with average delays of 2, 4, 2 and 6 months, respectively,
      which explained 56% of the observed variation in VRE rates over time. Efforts to
      reduce VRE cross-transmission should be supplemented by targeted antibiotic
      control policies. The use of glycopeptides, broad-spectrum cephalosporins and
      fluoroquinolones in high amounts should be the targets of such policies.
      Penicillin-beta-lactamase inhibitor combinations might be suitable substitutes
      for extended-spectrum cephalosporins.

PMID- 18727799
TI  - Metallo-beta-lactamase-producing Pseudomonas aeruginosa isolated from a large
      tertiary centre in Kenya.
AB  - This study was designed to characterize the beta-lactamase content of carbapenem
      resistant Pseudomonas aeruginosa isolates recovered during 2006 and 2007 in a
      large tertiary-care centre in Nairobi, Kenya. Molecular characterization was done
      using PCR and sequencing, and typing was performed using pulsed-field gel
      electrophoresis (PFGE). In total, 416 P. aeruginosa isolates were obtained during
      that period, of which 57 (13.7%) were resistant to carbapenems. All carbapenem
      resistant isolates tested positive for metallo-beta-lactamase (MBL) production.
      All MBL isolates produced VIM-2 with two types of integron structures. PFGE
      identified three clonally related groups of VIM-2-producing P. aeruginosa,
      including a pan-resistant clone that was responsible for nosocomial outbreaks
      during 2006 and 2007 in the intensive-care unit. These findings suggest that
      continuous molecular surveillance needs to be performed to monitor the spread
      within the hospital of this pan-resistant strain. This study is the first report
      of VIM-2-producing P. aeruginosa from the African continent.

PMID- 18727800
TI  - Resistance to fluoroquinolones by the combination of target site mutations and
      enhanced expression of genes for efflux pumps in Shigella flexneri and Shigella
      sonnei strains isolated in Korea.
AB  - Among 5938 clinical Shigella spp. isolates, two S. flexneri strains were isolated
      as those resistant to fluoroquinolones based on the MICs of the following
      antibiotics: ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin and
      levofloxacin. S. flexneri 021787 had three substitutions, one in GyrA (Ser83Leu)
      and two in ParC (Ser80Ile and Arg91Gln). S. flexneri 021895 had four
      substitutions, two in GyrA (Ser83Leu and Asp87Gly) and two in ParC (Ser80Ile and
      Arg91Gln). The increased susceptibility of S. flexneri 021787 and S. flexneri
      021895 to ciprofloxacin, norfloxacin and ofloxacin in the presence of the
      uncoupler carbonyl cyamide-m-chlorophenyldrazone implied that energy-dependent
      active efflux pumps contributed to the resistance against fluoroquinolones. Both
      S. flexneri 021787 and S. flexneri 021895 were also induced to express tolC
      (encoding a resistance-nodulation-division transporter), mdfA (encoding a major
      facilitator superfamily transporter), and ydhE (encoding a multidrug and toxic
      compound extrusion transporter) in the presence of ciprofloxacin. Thus, these
      results indicated that chromosome-mediated fluoroquinolone resistance of S.
      flexneri 021787 and S. flexneri 021895 resulted from the combination of target
      site mutations and enhanced expression of genes encoding efflux pumps.

PMID- 18727801
TI  - Activities of antistaphylococcal antibiotics towards the extracellular and
      intraphagocytic forms of Staphylococcus aureus isolates from a patient with
      persistent bacteraemia and endocarditis.
AB  - Decreased susceptibility of Staphylococcus aureus to antistaphylococcal agents
      may be associated with inability to eradicate intracellular forms, which could
      explain therapeutic failures. This hypothesis was tested using clinical isolates
      obtained from a patient with persistent staphylococcal bacteraemia under therapy.
      Four isogenic isolates (three from tissue, one from blood) with increased MICs
      for vancomycin (1-4 mg/L) and for daptomycin (1-4 mg/L) were collected after an
      initial 16-day treatment with vancomycin-rifampicin-gentamicin, followed by 13-20
      days of treatment with daptomycin-rifampicin-gentamicin. Isolates were tested for
      MICs and for: (i) vancomycin (BODIPY-FL-vancomycin) and daptomycin binding; (ii)
      cell wall turnover (loss of N-acetyl-d-[1-(14)C]glucosamine in 30 min after 1 h
      of labelling); and (iii) Triton X-100-induced autolysis. Extracellular (broth)
      and intracellular (THP-1 macrophages) activities of rifampicin, linezolid and
      fusidic acid at C(max), and of vancomycin, daptomycin, quinupristin-dalfopristin
      and oritavancin over a wide range of extracellular concentrations (with
      pharmacological modelling to determine E(max)), were measured at 24 h. Increases
      in vancomycin MICs correlated with increased drug binding, and decreased cell
      wall turnover and detergent-induced autolysis. Increases in daptomycin MICs
      correlated with decreased daptomycin binding. Intracellular activity was weak
      (E(max) <1 log(10) CFU decrease) for vancomycin against all isolates, and for
      daptomycin against isolates with MICs >1 mg/L. Among all antibiotics tested, only
      quinupristin-dalfopristin and oritavancin provided close to bactericidal
      intracellular activities (1.6-2.5 log(10) CFU decreases at C(max)). Determination
      of the intracellular susceptibility of S. aureus, combined with improved methods
      of diagnosis, could be useful when dealing with persistent staphylococcal
      infections and could improve therapy.

PMID- 18727802
TI  - Validation of PCR-reverse line blot, a method for rapid detection and
      identification of nine dermatophyte species in nail, skin and hair samples.
AB  - A dermatophyte-specific PCR-reverse line blot (PCR-RLB) assay based on internal
      transcribed sequences was developed. This assay allows the rapid detection and
      identification of nine clinically relevant species within the three dermatophyte
      genera Trichophyton, Microsporum and Epidermophyton in nail, skin and hair
      samples within 1 day. Analysis of 819 clinical samples (596 nail, 203 skin and 20
      hair) revealed a positive PCR-RLB result in 93.6% of 172 culture-positive and
      microscopy-positive samples. PCR-RLB was superior to culture and direct
      microscopy, in both detection and species identification. Comparison of
      identification results of 208 PCR-positive and culture-positive clinical samples
      showed five discrepancies (2.4%) between PCR-RLB identification and classical
      microscopic/biochemical identification of isolates. Comparison of PCR-RLB
      identification and classical identification of 98 other isolates (dermatophytes
      and non-dermatophytes) revealed 13 discrepancies (13.3%) and five incomplete
      identifications of Trichophyton spp. Sequence analysis of ITS1 regions of 23
      samples with discrepant or incomplete identification results (four Centraalbureau
      voor Schimmelcultures dermatophyte strains, four clinical samples and 15 clinical
      isolates) confirmed identification results of PCR-RLB in 21 of the 23 analyzed
      samples. PCR-RLB proved to be extremely suitable for routine detection and
      identification of dermatophytes directly in nail, skin and hair samples because
      it is rapid, sensitive, specific and accurate.

PMID- 18727803
TI  - Antimicrobial resistance in invasive strains of Escherichia coli from southern
      and eastern Mediterranean laboratories.
AB  - From January 2003 to December 2005, 5091 susceptibility test results from
      invasive isolates of Escherichia coli, collected from blood cultures and
      cerebrospinal fluid routinely processed within 58 participating laboratories,
      were investigated. These laboratories in turn serviced 64 hospitals in Algeria,
      Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey. The median
      proportion of resistance to third-generation cephalosporins for the duration of
      the project was 18.9% (interquartile range (IQR): 12.5-30.8%), and for
      fluoroquinolones 21.0% (IQR: 7.7-32.6%). A substantial proportion of strains
      reported by laboratories in countries east of the Mediterranean exhibited
      evidence of multiresistance, the highest proportion being from Egypt (31%). There
      is clearly a need for further investigation of potential causes of the
      significant resistance identified, as well as for strengthening of national and
      international surveillance initiatives within this region.;

PMID- 18727804
TI  - Antibiotic susceptibility and molecular epidemiology of nasopharyngeal
      pneumococci from Spanish children.
AB  - Nasopharyngeal pneumococci were collected from 635 Spanish children aged 6 months
      to 6 years attending four primary healthcare centres (n = 276) or two hospital
      emergency rooms (n = 359); 36% of the children had received >/=1 dose of
      pneumococcal conjugate vaccine (PCV7). Overall, the carriage rate of
      Streptococcus pneumoniae was 31%, with no significant differences in carriage
      rates according to setting. Colonization with vaccine serotypes was significantly
      associated with the absence of PCV7 immunization (29.4% vs. 5.9%, p <0.001).
      Forty-seven per cent of all isolates were penicillin- and/or erythromycin-non
      susceptible; 13 international antibiotic-resistant clones were represented among
      non-susceptible pneumococci and were similarly distributed among vaccine and non
      vaccine serotypes.

PMID- 18727805
TI  - Activity of moxifloxacin against the urogenital mycoplasmas Ureaplasma spp.,
      Mycoplasma hominis and Mycoplasma genitalium and Chlamydia trachomatis.
AB  - The activity of moxifloxacin was compared with that of other antimicrobial agents
      against 54 strains of Ureaplasma spp., 54 strains of Mycoplasma hominis, 14
      strains of Mycoplasma genitalium, and 44 strains of Chlamydia trachomatis.
      Moxifloxacin inhibited 90% of all isolates at a concentration </=1 mg/L, being
      the most active compound against C. trachomatis and sharing the highest activity
      with garenoxacin and gemifloxacin against mycoplasmas. Moxifloxacin killed the 30
      mycoplasma isolates tested at a concentration </=1 mg/L, except those resistant
      to fluoroquinolone. Thus, moxifloxacin has attracted interest as a potential
      therapy for mycoplasmal or chlamydial urogenital infections.

PMID- 18727806
TI  - Occupational infection due to Brucella abortus S19 among workers involved in
      vaccine production in Argentina.
AB  - The pathological consequences of exposure to the vaccine strain Brucella abortus
      S19 were evaluated in 30 employees from vaccine-manufacturing plants. Active
      brucellosis was diagnosed in 21 subjects, of whom only five recalled an
      accidental exposure. Clinical manifestations were mild, and only one patient
      presented a complication. After antimicrobial therapy, initially symptomatic
      patients either experienced clinical remission or had mild persistent symptoms.
      This is the first study reporting infection by B. abortus S19 among workers from
      vaccine-manufacturing plants, which in many cases was acquired from unnoticed
      exposures. Measures to improve the safety of B. abortus S19 handling should be
      implemented.

PMID- 18727807
TI  - Prevalence of emm types 1 and 12 from invasive Streptococcus pyogenes disease in
      Greece--results of enhanced surveillance.
AB  - Among a total of 101 isolates from the first systematic multicentre surveillance
      effort concerning invasive Streptococcus pyogenes disease in Greece, conducted
      between 2003 and 2005 and covering 38% of the population, emm types 1 and 12 were
      prevalent, being responsible for 27 and nine cases, respectively. The isolates
      from the remaining 65 cases were assigned to 26 other emm types. Erythromycin
      resistance (12 isolates) was primarily mef(A)-mediated, although all emm type 1
      strains were susceptible. Tetracycline resistance, due mostly to tet(M), was
      detected in 26 isolates. Subtyping by pulsed-field gel electrophoresis yielded 50
      chromosomal fingerprints, thus discriminating further among ten of the 28
      observed emm types.

PMID- 18727808
TI  - Identification of progenitor cancer stem cell in lentigo maligna melanoma.
AB  - The potential role of stem cells in neoplasia has aroused considerable interest
      over the past few years. A number of known biologic characteristics of melanomas
      support the theory that they may originate in a mutated stem cell. Melanocytic
      stem cell markers have been described recently. Moreover, the CD133 cells that
      show surface markers for CD34 are stem cells primitive. These stem cells are
      capable of differentiating into neurons, glia, keratinocytes, smooth muscle
      cells, and melanocytes in vitro. The identification of cancer stem/initiating
      cells with a crucial role in tumor formation may open up new pharmacologic
      perspectives. The purpose of this study is to detect the expression of CD133 and
      CD34, two putative markers of cancer stem cells in the lentigo maligna melanoma.
      Thirty cases of lentigo maligna melanoma were analyzed using indirect
      immunohistochemical staining. The vast majority of the samples analyzed showed
      the presence of rare cells, which were clearly positive for CD133 and CD34.
      Strong CD133 and CD34 staining was found in the outer root sheath of the mid
      lower hair follicles, intermixed with atypical melanocytes extending along layers
      of the hair follicles. A number of these staminal cells were adjacent and
      intermixed with melanoma cells. This study supports the stem cell origin of this
      tumor and suggests that the precursor of the melanoma in question is a stem-like
      cell rather than the primitive melanoblast committed to be exclusively involved
      in melanocytic differentiation.

PMID- 18727809
TI  - Nicolau syndrome following intramuscular diclofenac injection: a case report.
AB  - Nicolau syndrome (NS) is a rare complication of intramuscular injection of
      various drugs which clinically presents with extensive necrosis of skin,
      subcutaneous and even muscle tissue. We describe a case of NS following
      intramuscular injection of diclofenac.

PMID- 18727810
TI  - Treatment of chronic venous leg ulcers by platelet gel.
AB  - Chronic venous leg ulcers (CVLU) are chronic wounds, associated with long
      standing venous hypertension, which have a poor prognosis for healing. In the
      process of wound healing the first step is represented by platelet aggregation
      and subsequent release of growth factors and other mediators, which play a key
      role in the repair response. Platelet gel (PG), a hemocomponent obtained by
      mixing platelets, thrombin, and calcium, is able, when applied topically, to
      release platelet mediators that likely favor CVLU healing. However,
      unstandardized protocols have been described in studies utilizing PG for the
      regeneration of a number of tissues, including CVLU; the relative clinical
      outcomes were hence highly variable. In our experience the topical use of PG,
      together with the strict adherence to the principles of good wound care, quickly
      promoted increased granulation tissue, followed by a complete CVLU
      epithelization. Although further studies and trials are needed to establish the
      major outcome affecting rules for optimal indications, preparation, and use of PG
      for CVLU treatment, PG can be undoubtedly considered a useful tool, able to
      improve the management of CVLU.

PMID- 18727811
TI  - Melasma: successful treatment with pidobenzone 4% (K5lipogel).
AB  - Melasma (a term derived from the Greek word "melas" meaning black) is an acquired
      blotchy, irregularly patterned, brown or sometimes gray brown hypermelanosis of
      the face and occasionally the neck. Its etiology is poorly understood but mainly
      related to sunlight and genetic predisposition. Melasma seems to be more frequent
      in darker skinned people, especially women. Its treatment is always difficult and
      the condition usually relapses. The treatment with pidobenzone 4% (K5 lipogel),
      twice per day for 16 weeks has proved to be safe and effective. Pidobenzone 4%
      lipogel, according to the present study, seems also to represent a useful,
      reliable, and safe treatment of the different types of melasma.

PMID- 18727812
TI  - Targeted and combination treatments for vitiligo. Comparative evaluation of
      different current modalities in 458 subjects.
AB  - The current treatment of vitiligo is not satisfactory according to the opinions
      of both the patient population and the dermatologists. Recently, combination
      therapies have been introduced, which are both systemic and targeted
      (microphototherapy). To evaluate the effects of topical treatments given alone or
      in combination with 311-nm narrow-band microphototherapy. We evaluated the
      efficacy and safety of: (1) 311-nm narrow-band microphototherapy;(2) tacrolimus
      0.1% ointment twice a day; (3) pimecrolimus 1% cream twice a day; (4)
      betamethasone dipropionate 0.05% cream twice a day; (5) calcipotriol ointment 50
      microg/g twice a day; and (6) 10%l-phenylalanine cream twice a day, for the
      treatment of exclusively vitiligo patches. A 311-nm narrow-band microphototherapy
      (Bioskin) was given alone or in combination with the above-mentioned popular
      local treatments. Four hundred and seventy patients suffering from vitiligo that
      affected less than 10% of the skin surface were evaluated. The patients were
      divided into 11 groups according to the selected treatment modalities. Four
      hundred and fifty-eight patients completed the study period of 6 months.
      Excellent repigmentation (> 75%) was achieved by 72% of the patients in group 1,
      76.5% in group 2, 76.1% in group 3, 90.2% in group 4, 75.6% in group 5, 74.8% in
      group 6, 61% in group 7, 54.6% in group 8, 71.2% in group 9, 59.1% in group 10,
      and 29.3% in group 11. Marked repigmentation (50-75%) was evident in 19.8% of the
      patients in group 1, 18.2% in group 2, 20.1% in group 3, 6.7% in group 4, 14.1%
      in group 5, 11.3% in group 6, 16.1% in group 7, 18.4% in group 8, 25% in group 9,
      10.6% in group 10, and 8.1% in group 11. Moderate results (25-50% repigmentation)
      were seen in 4.6% of the patients in group 1, 3.3% in group 2, 2.7% in group 3,
      2.2% in group 4, 7.4% in group 5, 10.1% in group 6, 18.4% in group 7, 21.7% in
      group 8, 2.1% in group 9, 27.1% in group 10, and 55% in group 11. Finally,
      minimal (< 25%) or no response was achieved in 3.6% of the patients in group 1,
      2% in group 2, 1.1% in group 3, 0.9% in group 4, 2.9% in group 5, 3.8% in group
      6, 4.5% in group 7, 5.3% in group 8, 1.75% in group 9, 3.2% in group 10, and 7.6%
      in group 11. Side effects were skin atrophy (76% in group 4 and 81% in group 9),
      stinging and burning (groups 2, 3, 7, and 8). Targeted combination therapies in
      vitiligo are remarkably more effective than single treatments. When single
      treatments are considered alone, 311-nm narrow-band UVB microfocused phototherapy
      and 0.05% betamethasone dipropionate cream are the most effective treatments in
      our study. When combined therapies are chosen, 0.05% betamethasone dipropionate
      cream plus 311-nm narrow-band UVB microfocused phototherapy apparently give the
      highest repigmentation rate. In the short term, the only side-effects registered
      have been cutaneous atrophy with corticosteroid cream, and stinging and burning
      with 0.1% tacrolimus ointment and, less frequently, with 1% pimecrolimus cream.

PMID- 18727813
TI  - An open-label tolerability and efficacy study of an aluminum sesquichlorohydrate
      topical foam in axillary and palmar primary hyperhidrosis.
AB  - Primary hyperidrosis (PH) is a disorder characterized by excessive eccrine sweat
      gland production that primarily involves the axillae as well as palms and soles.
      Common first-line topical treatment for PH consists of aluminum salts (AS) that
      act by physically blocking eccrine sweat gland ducts. However, primary irritant
      contact dermatitis is a common side effect of AS treatment. Recently, a new low
      residue, thermophobic foam formulation containing 20% aluminum
      sesquichlorohydrate has been developed (Nidrox, Mipharm S.p.A.). To evaluate the
      local tolerability and efficacy of 20% aluminum sesquichlorohydrate foam in the
      treatment of axillary and palmar PH. Twenty subjects affected by PH were enrolled
      in a multicenter, open-label study. Local tolerability was evaluated by
      physicians assessing itching, burning, and skin irritation using a four-point
      score (from 0: no symptoms to 3: severe symptoms). Skin irritation was quantified
      with a visual score. Efficacy was assessed by means of Minor test score using a
      four-point score (range 0-3). The foam was applied to clean dry skin, every night
      during the first 2 weeks and three times a week during the following 2 weeks.
      Clinical evaluations were performed at baseline, at day 14 and at day 28.
      Patients were monitored throughout the study for adverse events. All 20 subjects
      completed the study. The foam induced a significant reduction of the Minor score
      in comparison with baseline values (p = 0.0002) both at day 14 and at day 28. At
      the end of the 4-week treatment period, the foam reduced eccrine sweating by 61%
      (Minor score: 3.3 vs. 8.5). No skin irritation was observed during the trial
      except for one subject who experienced a mild and transient itching sensation. No
      other side effects were reported during the study. This new foam appears to be an
      effective and well-tolerated topical treatment in reducing sweating in patients
      with axillary and palmar PH.

PMID- 18727814
TI  - Balneotherapy for chronic plaque psoriasis at Comano spa in Trentino, Italy.
AB  - Thermal therapy is used worldwide in the treatment of psoriasis but few
      controlled studies have evaluated its efficacy and safety. We studied the
      efficacy and safety of balneotherapy compared to photobalneotherapy performed at
      Comano spa in Trentino, Italy, in chronic plaque psoriasis in a prospective,
      nonrandomized, open study. Three hundred adult patients with mild to severe
      chronic plaque psoriasis were assigned to either balneotherapy or
      photobalneotherapy with daily narrow-band ultraviolet B for a mean period of 1 or
      2 weeks, reflecting the times that most patients can dedicate to thermal therapy.
      Patients were evaluated at baseline and end of treatment for psoriasis area and
      severity index (PASI) and body surface area; self-administered PASI (SAPASI) and
      Skindex-29 were evaluated at the same times, and also at 4 months by a mailed
      questionnaire. One-week balneotherapy or photobalneotherapy resulted in a
      significant reduction in PASI score (11.54% +/- 2.76 and 12.76% +/- 3.79,
      respectively; mean +/- standard deviation; p < 0.001). Two-week therapy induced a
      greater response with photobalneotherapy than with balneotherapy alone, with PASI
      reduction of 19.8% +/- 24.5 and 13.5% +/- 23.1 (p < 0.005), respectively. These
      results were confirmed by SAPASI and Skindex-29 evaluation. The therapy was well
      tolerated. Skin improvement was mostly lost after 4 months. Short-term
      balneotherapy and photobalneotherapy could thus be offered to patients willing to
      temporarily discontinue pharmacologic therapy or as adjuvant therapy.

PMID- 18727815
TI  - Rituximab in refractory pemphigus vulgaris.
AB  - Pemphigus vulgaris (PV) is a severe chronic autoimmune blistering disease of skin
      and mucous membranes. The use of systemic corticosteroids in pemphigus has
      dramatically reduced its mortality rate, but the long-term use of steroids leads
      to severe side effects, many of which are serious. For this reason it is often
      necessary to add immunosuppressive agents to the regimen. However, there are
      occasional refractory cases in which therapy with conventionally accepted
      modalities is either not efficacious or not possible on account of side effects.
      Rituximab is a therapeutic monoclonal antibody targeting CD20, an integral
      membrane protein highly expressed on the surface of pre-B lymphocytes and
      activated mature B lymphocytes. We present an instance of refractory PV
      successfully treated with rituximab. The successful treatment of pemphigus
      described here demonstrates that rituximab is a viable therapeutic option for
      patients with refractory PV.

PMID- 18727816
TI  - Reproducibility of 3-dimensional ultrasound readings of volume of carotid
      atherosclerotic plaque.
AB  - BACKGROUND: Non-invasive 3-dimensional (3D) ultrasound (US) has emerged as the
      predominant approach for evaluating the progression of carotid atherosclerosis
      and its response to treatment. The aim of this study was to investigate the
      quality of a central reading procedure concerning plaque volume (PV), measured by
      3D US in a multinational US trial. METHODS: Two data sets of 45 and 60 3D US
      patient images of plaques (mean PV, 71.8 and 39.8 mul, respectively) were used.
      PV was assessed by means of manual planimetry. The intraclass correlation
      coefficient (ICC) was applied to determine reader variabilities. The
      repeatability coefficient (RC) and the coefficient of variation (CV) were used to
      investigate the effect of number of slices (S) in manual planimetry and plaque
      size on measurement variability. RESULTS: Intra-reader variability was small as
      reflected by ICCs of 0.985, 0.967 and 0.969 for 3 appointed readers. The ICC
      value generated between the 3 readers was 0.964, indicating that inter-reader
      variability was small, too. Subgroup analyses showed that both intra- and inter
      reader variabilities were lower for larger than for smaller plaques. Mean CVs
      were similar for the 5S- and 10S-methods with a RC of 4.7 microl. The RC between
      both methods as well as the CVs were comparatively lower for larger plaques.
      CONCLUSION: By implementing standardised central 3D US reading protocols and
      strict quality control procedures highly reliable ultrasonic re-readings of
      plaque images can be achieved in large multicentre trials.

PMID- 18727817
TI  - Recombination and selectional forces in cyanopeptolin NRPS operons from highly
      similar, but geographically remote Planktothrix strains.
AB  - BACKGROUND: Cyanopeptolins are nonribosomally produced heptapetides showing a
      highly variable composition. The cyanopeptolin synthetase operon has previously
      been investigated in three strains from the genera Microcystis, Planktothrix and
      Anabaena. Cyanopeptolins are displaying protease inhibitor activity, but the
      biological function(s) is (are) unknown. Cyanopeptolin gene cluster variability
      and biological functions of the peptide variants are likely to be interconnected.
      RESULTS: We have investigated two cyanopeptolin gene clusters from highly
      similar, but geographically remote strains of the same genus. Sequencing of a
      nonribosomal peptide synthetase (NRPS) cyanopeptolin gene cluster from the
      Japanese strain Planktothrix NIES 205 (205-oci), showed the 30 kb gene cluster to
      be highly similar to the oci gene cluster previously described in Planktothrix
      NIVA CYA 116, isolated in Norway. Both operons contained seven NRPS modules, a
      sulfotransferase (S) and a glyceric acid loading (GA)-domain. Sequence analyses
      showed a high degree of conservation, except for the presence of an epimerase
      domain in NIES 205 and the regions around the epimerase, showing high
      substitution rates and Ka/Ks values above 1. The two strains produce almost
      identical cyanopeptolins, cyanopeptolin-1138 and oscillapeptin E respectively,
      but with slight differences regarding the production of minor cyanopeptolin
      variants. These variants may be the result of relaxed adenylation (A)-domain
      specificity in the nonribosomal enzyme complex. Other genetic markers (16S rRNA,
      ntcA and the phycocyanin cpcBA spacer) were identical, supporting that these
      geographically separated Planktothrix strains are closely related. CONCLUSION: A
      horizontal gene transfer event resulting in exchange of a whole module-encoding
      region was observed. Nucleotide statistics indicate that both purifying selection
      and positive selection forces are operating on the gene cluster. The positive
      selection forces are acting within and around the epimerase insertion while
      purifying selection conserves the remaining (major) part of the gene cluster. The
      presence of an epimerase in the gene cluster is in line with the D-configuration
      of Htyr, determined experimentally in oscillapeptin E in a previous study.

PMID- 18727818
TI  - Spontaneous infection of a stable mediastinal cystic mass: A case report.
AB  - Mediastinal cysts have an unpredictable course but can cause complications such
      as infection or local pressure effects. Persons with mediastinal cysts can be
      asymptomatic for many years or can develop symptoms as a result of complications
      of the cyst. There is a lack of consensus on the best approach to managing those
      patients without symptoms. In this case report, a 56 year old woman with an
      indolent mediastinal cyst initially managed conservatively suddenly developed
      symptoms suggestive of an infected mediastinal cyst requiring surgical resection.

PMID- 18727819
TI  - Ureteral fibroepithelial polyps with calculi: a case series.
AB  - INTRODUCTION: Fibroepithelial polyps of the ureter are benign tumors arising from
      the mesodermal tissue in the ureteral wall. Their etiology remains unknown.
      Hematuria and obstructive urinary symptoms are the most common findings. The
      treatment of choice is endoscopic resection, and the prognosis for patients with
      these lesions is excellent. CASE PRESENTATION: We present three cases of
      fibroepithelial polyps associated with calculi in the distal part of the ureter.
      The patients were all women, aged 20, 45 and 52 years. Two patients were
      suffering from flank pain and dysuria while one patient was asymptomatic at the
      time of diagnosis. The patients were fully treated with endoscopic resection. To
      the best of our knowledge, this is the fourth report of adult ureteral
      fibroepithelial polyps associated with ureteral calculi in the English
      literature. The etiology, clinical features, diagnosis, and management of
      fibroepithelial polyps are discussed in this report. CONCLUSION: Whenever
      polypoid lesions are detected especially at the distal part of the ureter, benign
      fibroepithelial polyps should be kept in mind for differential diagnosis.
      Additionally, although rarely seen, the co-existence of ureteral calculi with
      fibroepithelial polyps should be borne in mind.

PMID- 18727820
TI  - Double dermal sinuses: a case study.
AB  - INTRODUCTION: Dermal sinus tracts are rare congenital lesions located in the
      midline characterized by a cutaneous pit or dimple. They occur all along the
      midline neuroaxis, from the nasion and occipital area down to the lumbar and
      sacral regions, most frequently in the lumbar and lumbosacral region. CASE
      PRESENTATION: Here we report a 5-year-old girl who presented with occasional
      headache. There were two dimples, one on the dorsal aspect of her head and
      another on her neck. CONCLUSION: Dermal sinuses are almost always singular and
      the co-existence of double dermal sinuses has not been reported previously.

PMID- 18727822
TI  - Disseminated cutaneous Herpes Simplex Virus-1 in a woman with rheumatoid
      arthritis receiving infliximab: a case report.
AB  - INTRODUCTION: We present the case of a 49-year-old woman with a seronegative
      rheumatoid arthritis who developed pustular psoriasis whilst on etanercept and
      subsequently developed disseminated herpes simplex on infliximab. CASE
      PRESENTATION: Our patient presented with an inflammatory arthritis which failed
      to respond to both methotrexate and leflunomide, and sulphasalazine treatment led
      to side effects. She was started on etanercept but after 8 months of treatment
      developed scaly pustular lesions on her palms and soles typical of pustular
      psoriasis. Following the discontinuation of etanercept, our patient required high
      doses of oral prednisolone to control her inflammatory arthritis. A second
      biologic agent, infliximab, was introduced in addition to low-dose methotrexate
      and 15 mg of oral prednisolone. However, after just 3 infusions of infliximab,
      she was admitted to hospital with a fever, widespread itchy vesicular rash and
      worsening inflammatory arthritis. Fluid from skin vesicles examined by polymerase
      chain reaction showed Herpes Simplex Virus type 1. Blood cultures were negative
      and her chest X-ray was normal. Her infliximab was discontinued and she was
      started on acyclovir, 800 mg five times daily for 2 weeks. She made a good
      recovery with improvement in her skin within 48 hours.She continued for 2 months
      on a prophylactic dose of 400 mg bd. Her rheumatoid arthritis became increasingly
      active and a decision was made to introduce adalimumab alongside acyclovir.
      Acyclovir prophylaxis has been continued but the dose tapered so that she is
      taking only 200 mg of acyclovir on alternate days. There has been no recurrence
      of Herpes Simplex Virus lesions despite increasing adalimumab to 40 mg weekly 3
      months after starting treatment. CONCLUSION: We believe this to be the first
      reported case of widespread cutaneous Herpes Simplex Virus type 1 infection
      following treatment with infliximab. We discuss the clinical manifestations of
      Herpes Simplex Virus infections with particular emphasis on the immunosuppressed
      patient and the use of prophylactic acyclovir. Pustular psoriasis is now a well
      recognised but uncommon side effect of antitumour necrosis factor therapy and can
      lead to cessation of therapy, as in our patient's case.

PMID- 18727821
TI  - Runx transcription factors in neuronal development.
AB  - Runt-related (Runx) transcription factors control diverse aspects of embryonic
      development and are responsible for the pathogenesis of many human diseases. In
      recent years, the functions of this transcription factor family in the nervous
      system have just begun to be understood. In dorsal root ganglion neurons, Runx1
      and Runx3 play pivotal roles in the development of nociceptive and proprioceptive
      sensory neurons, respectively. Runx appears to control the transcriptional
      regulation of neurotrophin receptors, numerous ion channels and neuropeptides. As
      a consequence, Runx contributes to diverse aspects of the sensory system in
      higher vertebrates. In this review, we summarize recent progress in determining
      the role of Runx in neuronal development.

PMID- 18727823
TI  - Ultra-brief intervention for problem drinkers: research protocol.
AB  - BACKGROUND: Helping the large number of problem drinkers who will never seek
      treatment is a challenging issue. Public health initiatives employing educational
      materials or mass media campaigns have met with mixed success. However, clinical
      research has developed effective brief interventions to help problem drinkers.
      This project will employ an intervention that has been validated in clinical
      settings and then modified into an ultra-brief format suitable for use as a
      public health intervention. The major objective of this study is to conduct a
      randomized controlled trial to establish the effectiveness of an ultra-brief,
      personalized feedback intervention for problem drinkers. METHODS/DESIGN: Problem
      drinkers recruited on a baseline population telephone survey conducted in a major
      metropolitan city in Canada will be randomized to one of three conditions - a
      personalized feedback pamphlet condition, a control pamphlet condition, or a no
      intervention control condition. In the week after the baseline survey, households
      in the two pamphlet conditions will be sent their respective pamphlets. Changes
      in drinking will be assessed post intervention at three-month and six-month
      follow-ups. Drinking outcomes will be compared between experimental conditions
      using Structural Equation Modeling. The primary hypothesis is that problem
      drinkers from households who receive the personalized feedback pamphlet
      intervention will display significantly improved drinking outcomes at three and
      six-month follow-ups as compared to problem drinkers from households in the no
      intervention control condition. Secondary hypotheses will test the impact of the
      intervention on help seeking, and explore the mediating or moderating role of
      perceived drinking norms, perceived alcohol risks and the problem drinker's
      social reasons for drinking. DISCUSSION: This trial will provide information on
      the effectiveness of a pamphlet-based personalized feedback intervention for
      problem drinkers in a community setting. TRIAL REGISTRATION: ClinicalTrials.gov
      registration #NCT00688584.

PMID- 18727824
TI  - Successful desensitization with human insulin in a patient with an insulin
      allergy and hypersensitivity to protamine: a case report.
AB  - INTRODUCTION: Insulin allergy may occur in patients treated with subcutaneous
      applications of insulin preparations. Besides additives in the insulin
      preparation such as protamine, cresol, and phenol, the insulin molecule itself
      may be the cause of the allergy. In the latter case, therapeutic options are
      rare. CASE PRESENTATION: A 68-year-old man with poorly controlled type 2 diabetes
      mellitus received different insulin preparations subcutaneously while on oral
      medication. Six to eight hours after each subcutaneous application, he developed
      pruritic plaques with a diameter of >15 cm at the injection sites that persisted
      for several days. Allergologic testing revealed positive reactions against every
      insulin preparation and against protamine. Investigation of serum samples
      demonstrated IgG antibodies against human and porcine insulin. We treated the
      patient with human insulin using an ultra-rush protocol beginning with 0.004 IU
      and a rapid augmentation in dose up to 5 IU. Therapy was accompanied by
      antihistamine therapy. Subsequent conversion to therapy with glargine insulin (6
      IE twice daily) was well-tolerated. CONCLUSION: As reported in this case,
      desensitization with subcutaneously administered human insulin using an ultra
      rush protocol in patients with an insulin allergy may present an easy form of
      therapy that is successful within a few days.

PMID- 18727825
TI  - Effect of the ethinylestradiol/norelgestromin contraceptive patch on body
      composition. Results of bioelectrical impedance analysis in a population of
      Italian women.
AB  - BACKGROUND: As weight gain is one of the most frequently cited reasons for not
      using and for discontinuing hormonal contraceptives, in an open-label, single
      arm, multicentre clinical study we evaluated the effect of the
      ethinylestradiol/norelgestromin contraceptive patch (EVRA, Janssen-Cilag
      International, Belgium) on body composition using bioelectrical impedance
      analysis (BIA). METHODS: Body weight and impedance vector components (resistance
      (R) and reactance (Xc), at 50 kHz frequency, Akern-RJL Systems analyzer) were
      recorded before entry, after 1, 3 and 6 months in 182 Italian healthy women aged
      29 yr (18 to 45), and with BMI 21.8 kg/m2 (16 to 31). Total body water (TBW) was
      estimated with a BIA regression equation. Vector BIA was performed with the RXc
      mean graph method and the Hotelling's T2 test for paired and unpaired data.
      RESULTS: After 6 months body weight increased by 0.64 kg (1.1%) and TBW increased
      by 0.51 L (1.7%). The pattern of impedance vector displacement indicated a small
      increase in soft tissue hydration (interstitial gel fluid). Body composition
      changes did not significantly differ among groups of previous contraceptive
      methods. Arterial blood pressure did not significantly change over time.
      CONCLUSION: After 6 months of treatment with the ethinylestradiol/norelgestromin
      contraceptive patch we found a minimal, clinically not relevant, increase in body
      weight less than 1 kg that could be attributed to an adaptive interstitial gel
      hydration. This fluctuation is physiological as confirmed by the lack of any
      effect on blood pressure. This could be useful in increasing women's choice,
      acceptability and compliance of the ethinylestradiol/norelgestromin contraceptive
      patch.

PMID- 18727826
TI  - Preferential regulation of duplicated genes by microRNAs in mammals.
AB  - BACKGROUND: Although recent advances have been made in identifying and analyzing
      instances of microRNA-mediated gene regulation, it remains unclear by what
      mechanisms attenuation of transcript expression through microRNAs becomes an
      integral part of post-transcriptional modification, and it is even less clear to
      what extent this process occurs for mammalian gene duplicates (paralogs).
      Specifically, while mammalian paralogs are known to overcome their initial
      complete functional redundancy through variation in regulation and expression,
      the potential involvement of microRNAs in this process has not been investigated.
      RESULTS: We comprehensively investigated the impact of microRNA-mediated post
      transcriptional regulation on duplicated genes in human and mouse. Using
      predicted targets derived from several analysis methods, we report the following
      observations: microRNA targets are significantly enriched for duplicate genes,
      implying their roles in the differential regulation of paralogs; on average,
      duplicate microRNA target genes have longer 3' untranslated regions than
      singleton targets, and are regulated by more microRNA species, suggesting a more
      sophisticated mode of regulation; ancient duplicates were more likely to be
      regulated by microRNAs and, on average, have greater expression divergence than
      recent duplicates; and ancient duplicate genes share fewer ancestral microRNA
      regulators, and recent duplicate genes share more common regulating microRNAs.
      CONCLUSION: Collectively, these results demonstrate that microRNAs comprise an
      important element in evolving the regulatory patterns of mammalian paralogs. We
      further present an evolutionary model in which microRNAs not only adjust
      imbalanced dosage effects created by gene duplication, but also help maintain
      long-term buffering of the phenotypic consequences of gene deletion or ablation.

PMID- 18727827
TI  - Testing for allergic disease: parameters considered and test value.
AB  - BACKGROUND: Test results for allergic disease are especially valuable to
      allergists and family physicians for clinical evaluation, decisions to treat, and
      to determine needs for referral. METHODS: This study used a repeated measures
      design (conjoint analysis) to examine trade offs among clinical parameters that
      influence the decision of family physicians to use specific IgE blood testing as
      a diagnostic aid for patients suspected of having allergic rhinitis. Data were
      extracted from a random sample of 50 family physicians in the Southeastern United
      States. Physicians evaluated 11 patient profiles containing four clinical
      parameters: symptom severity (low, medium, high), symptom length (5, 10, 20
      years), family history (both parents, mother, neither), and medication use
      (prescribed antihistamines, nasal spray, over-the-counter medications). Decision
      to recommend specific IgE testing was elicited as a "yes" or "no" response.
      Perceived value of specific IgE blood testing was evaluated according to
      usefulness as a diagnostic tool compared to skin testing, and not testing.
      RESULTS: The highest odds ratios (OR) associated with decisions to test for
      allergic rhinitis were obtained for symptom severity (OR, 12.11; 95%CI, 7.1-20.7)
      and length of symptoms (OR, 1.46; 95%CI, 0.96-2.2) with family history having
      significant influence in the decision. A moderately positive association between
      testing issues and testing value was revealed (beta = 0.624, t = 5.296, p < or =
      0.001) with 39% of the variance explained by the regression model. CONCLUSION:
      The most important parameters considered when testing for allergic rhinitis
      relate to symptom severity, length of symptoms, and family history. Family
      physicians recognize that specific IgE blood testing is valuable to their
      practice.

PMID- 18727828
TI  - Ischemic stroke risk, smoking, and the genetics of inflammation in a biracial
      population: the stroke prevention in young women study.
AB  - BACKGROUND: Although cigarette smoking is a well-established risk factor for
      vascular disease, the genetic mechanisms that link cigarette smoking to an
      increased incidence of stroke are not well understood. Genetic variations within
      the genes of the inflammatory pathways are thought to partially mediate this
      risk. Here we evaluate the association of several inflammatory gene single
      nucleotide polymorphisms (SNPs) with ischemic stroke risk among young women,
      further stratified by current cigarette smoking status. METHODS: A population
      based case-control study of stroke among women aged 15-49 identified 224 cases of
      first ischemic stroke (47.3% African-American) and 211 age-comparable control
      subjects (43.1% African-American). Several inflammatory candidate gene SNPs
      chosen through literature review were genotyped in the study population and
      assessed for association with stroke and interaction with smoking status.
      RESULTS: Of the 8 SNPs (across 6 genes) analyzed, only IL6 SNP rs2069832 (allele
      C, African-American frequency = 92%, Caucasian frequency = 55%) was found to be
      significantly associated with stroke using an additive model, and this was only
      among African-Americans (age-adjusted: OR = 2.2, 95% CI = 1.0-5.0, p = 0.049;
      risk factor adjusted: OR = 2.5, 95% CI = 1.0-6.5, p = 0.05). When stratified by
      smoking status, two SNPs demonstrated statistically significant gene-environment
      interactions. First, the T allele (frequency = 5%) of IL6 SNP rs2069830 was found
      to be protective among non-smokers (OR = 0.30, 95% CI = 0.11-.082, p = 0.02), but
      not among smokers (OR = 1.63, 95% CI = 0.48-5.58, p = 0.43); genotype by smoking
      interaction (p = 0.036). Second, the C allele (frequency = 39%) of CD14 SNP
      rs2569190 was found to increase risk among smokers (OR = 2.05, 95% CI = 1.09
      3.86, p = 0.03), but not among non-smokers (OR = 0.93, 95% CI = 0.62-1.39, p =
      0.72); genotype by smoking interaction (p = 0.039). CONCLUSION: This study
      demonstrates that inflammatory gene SNPs are associated with early-onset ischemic
      stroke among African-American women (IL6) and that cigarette smoking may modulate
      stroke risk through a gene-environment interaction (IL6 and CD14). Our finding
      replicates a prior study showing an interaction with smoking and the C allele of
      CD14 SNP rs2569190.

PMID- 18727830
TI  - Ectopic internal carotid artery presenting as an oropharyngeal mass.
AB  - Ectopic internal carotid artery (ICA) is a very rare variation. The major
      congenital abnormalities of the ICA can be classified as agenesis, aplasia and
      hypoplasia, and they can be unilateral or bilateral. Anomalies of the neck artery
      may be vascular neoplasms or ectopic position. Carotid angiograms provide
      absolute confirmation of an aberrant carotid artery, while EcoColorDoppler (ECD)
      gives also important information about the evaluation of carotid vassels.
      Nevertheless Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) of the
      neck provide spatial information about the adjacent pharyngeal anatomy and are
      less invasive than angiogram. Injuries to the ICA during simple pharyngeal
      surgical procedures can be catastrophic due to the risk of massive bleeding. We
      report a case of a 56 year-old male patient suffering from dysphagia associated
      with aberrant ICA manifesting itself as a pulsative protruding of the left
      lateral wall of the oropharynx.

PMID- 18727829
TI  - Dorsal turning of motor corticospinal axons at the pyramidal decussation requires
      plexin signaling.
AB  - BACKGROUND: The development of the corticospinal tract (CST) in higher
      vertebrates relies on a series of axon guidance decisions along its long
      projection pathway. Several guidance molecules are known to be involved at
      various decision points to regulate the projection of CST axons. However,
      previous analyses of the CST guidance defects in mutant mice lacking these
      molecules have suggested that there are other molecules involved in CST axon
      guidance that are yet to be identified. In this study, we investigate the role of
      plexin signaling in the guidance of motor CST axons in vivo. RESULTS: Expression
      pattern studies show that plexin-A3, plexin-A4, and neuropilin-1 are expressed in
      the developing cerebral cortex when the motor CST axons originating from layer V
      cortical neurons are guided down to the spinal cord. By analyzing mutant mice, we
      show that motor CST axons that turn dorsally to cross the midline at the
      pyramidal decussation require plexin-A3 and plexin-A4 signaling. Although other
      CST guidance defects are found in neuropilin-1 mutants, this dorsal turning
      defect is not observed in either neuropilin-1 or neuropilin-2 mutants, suggesting
      that the local cues that activate plexin signaling at the dorsal turning point
      are membrane-bound semaphorins. Further expression pattern study and mutant
      analysis indicate that Sema6A is one of the local cues for motor CST axon turning
      at the pyramidal decussation. CONCLUSION: Dorsal turning and midline crossing at
      the pyramidal decussation is a crucial step to properly direct CST axons into the
      dorsal spinal cord. We show that the signaling of plexin-A3, plexin-A4, and
      Sema6A is at least partially required for dorsal turning of the CST axons, while
      neuropilin-1 is required for proper fasciculation of the tract at midline
      crossing. Together with previous reports, these results demonstrate that several
      guidance cues are specifically utilized to regulate the dorsal turning and
      midline crossing of developing CST axons.

PMID- 18727832
TI  - Risk factors for falls with severe fracture in elderly people living in a middle
      income country: a case control study.
AB  - BACKGROUND: Fracture after falling has been identified as an important problem in
      public health. Most studies of risk factors for fractures due to falls have been
      carried out in developed countries, although the size of the elderly population
      is increasing fast in middle income countries. The objective of this paper is to
      identify risk factors for fall related to severe fractures in those aged 60 or
      more in a middle-income country. METHODS: A case-control study was carried out in
      Rio de Janeiro-Brazil based general hospitals between 2002-2003. Two hundred
      fifty hospitalised cases of fracture were matched with 250 community controls by
      sex, age group and living area. Data were collected for socio-demographic
      variables, health status and drugs used before the fall. A conditional logistic
      regression model was fitted to identify variables associated with the risk of
      fall related severe fracture. RESULTS: Low body mass index, cognitive impairment,
      stroke and lack of urine control were associated with increased risk of severe
      fall related fractures. Benzodiazepines and muscle relaxants were also related to
      an increased risk of severe fractures while moderate use of alcohol was
      associated with reduced risk. CONCLUSION: Although the association between
      benzodiazepines and fractures due to fall has been consistently demonstrated for
      old people, this has not been the case for muscle relaxant drugs. The decision to
      prescribe muscle relaxants for elderly people should take into account the risk
      of severe fracture associated with these drugs.

PMID- 18727831
TI  - Costs of treating patients with schizophrenia who have illness-related crisis
      events.
AB  - BACKGROUND: Relatively little is known about the relationship between
      psychosocial crises and treatment costs for persons with schizophrenia. This
      naturalistic prospective study assessed the association of recent crises with
      mental health treatment costs among persons receiving treatment for
      schizophrenia. METHODS: Data were drawn from a large multi-site, non
      interventional study of schizophrenia patients in the United States, conducted
      between 1997 and 2003. Participants were treated at mental health treatment
      systems, including the Department of Veterans Affairs (VA) hospitals, community
      mental health centers, community and state hospitals, and university health care
      service systems. Total costs over a 1-year period for mental health services and
      component costs (psychiatric hospitalizations, antipsychotic medications, other
      psychotropic medications, day treatment, emergency psychiatric services,
      psychosocial/rehabilitation group therapy, individual therapy, medication
      management, and case management) were calculated for 1557 patients with complete
      medical information. Direct mental health treatment costs for patients who had
      experienced 1 or more of 5 recent crisis events were compared to propensity
      matched samples of persons who had not experienced a crisis event. The 5 non
      mutually exclusive crisis event subgroups were: suicide attempt in the past 4
      weeks (n = 18), psychiatric hospitalization in the past 6 months (n = 240),
      arrest in the past 6 months (n = 56), violent behaviors in the past 4 weeks (n =
      62), and diagnosis of a co-occurring substance use disorder (n = 413). RESULTS:
      Across all 5 categories of crisis events, patients who had a recent crisis had
      higher average annual mental health treatment costs than patients in propensity
      score matched comparison samples. Average annual mental health treatment costs
      were significantly higher for persons who attempted suicide ($46,024), followed
      by persons with psychiatric hospitalization in the past 6 months ($37,329),
      persons with prior arrests ($31,081), and persons with violent behaviors
      ($18,778). Total cost was not significantly higher for those with co-occurring
      substance use disorder ($19,034). CONCLUSION: Recent crises, particularly suicide
      attempts, psychiatric hospitalizations, and criminal arrests, are predictive of
      higher mental health treatment costs in schizophrenia patients.

PMID- 18727833
TI  - Serum lipid responses to psyllium fiber: differences between pre- and post
      menopausal, hypercholesterolemic women.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of death in women and
      men. Psyllium, a soluble fiber has been known to reduce serum lipids. In this
      pilot study, we evaluated whether menopausal status would affect the serum lipid
      responses to psyllium fiber in women. METHODS: Eleven post-menopausal and eight
      pre-menopausal women with serum total cholesterol >200 mg/dL were included in the
      study. Subjects consumed their habitual diet and 15 g psyllium/d for 6 weeks.
      Psyllium was incorporated into cookies. Each cookie contained approximately 5 g
      of psyllium fiber. Subjects ate one cookie in each meal. RESULTS: With psyllium
      fiber, total cholesterol concentration was significantly lower ( approximately
      5.2%, P < 0.05) in post-menopausal women but not in pre-menopausal women (
      approximately 1.3%). Also, there was a significant decrease in HDL-cholesterol in
      post-menopausal women ( approximately 10.2%, P < 0.05). There were no significant
      changes observed in concentrations of LDL-cholesterol, triglycerides,
      apolipoprotein A1, and apolipoprotein B in both pre- and post-menopausal women
      with psyllium. CONCLUSION: In this pilot study, post- and pre-menopausal,
      hypercholesterolemic women responded differently to psyllium fiber
      supplementation. Post-menopausal women would benefit from addition of psyllium to
      their diets in reducing the risk for heart diseases. The results of this study
      should be used with caution because the study was based on a small sample size.

PMID- 18727834
TI  - Changes in clot lysis levels of reteplase and streptokinase following continuous
      wave ultrasound exposure, at ultrasound intensities following attenuation from
      the skull bone.
AB  - BACKGROUND: Ultrasound (US) has been used to enhance thrombolytic therapy in the
      treatment of stroke. Considerable attenuation of US intensity is however noted if
      US is applied over the temporal bone. The aim of this study was therefore to
      explore possible changes in the effect of thrombolytic drugs during low
      intensity, high-frequency continuous-wave ultrasound (CW-US) exposure. METHODS:
      Clots were made from fresh venous blood drawn from healthy volunteers. Each clot
      was made from 1.4 ml blood and left to coagulate for 1 hour in a plastic test
      tube. The thrombolytic drugs used were, 3600 IU streptokinase (SK) or 0.25 U
      reteplase (r-PA), which were mixed in 160 ml 0.9% NaCl solution. Continuous-wave
      US exposure was applied at a frequency of 1 MHz and intensities ranging from
      0.0125 to 1.2 W/cm2. For each thrombolytic drug (n = 2, SK and r-PA) and each
      intensity (n = 9) interventional clots (US-exposed, n = 6) were submerged in
      thrombolytic solution and exposed to CW-US while control clots (also submerged in
      thrombolytic solution, n = 6) were left unexposed to US.To evaluate the effect on
      clot lysis, the haemoglobin (Hb) released from each clot was measured every 20
      min for 1 hour (20, 40 and 60 min). The Hb content (mg) released was estimated by
      spectrophotometry at 540 nm. The difference in effect on clot lysis was expressed
      as the difference in the amount of Hb released between pairs of US-exposed clots
      and control clots. Statistical analysis was performed using Wilcoxon's signed
      rank test. RESULTS: Continuous-wave ultrasound significantly decreased the
      effects of SK at intensities of 0.9 and 1.2 W/cm2 at all times (P < 0.05).
      Continuous-wave ultrasound significantly increased the effects of r-PA on clot
      lysis following 20 min exposure at 0.9 W/cm2 and at 1.2 W/cm2, following 40 min
      exposure at 0.3, 0.6, 0.9 and at 1.2 W/cm2, and following 60 min of exposure at
      0.05 0.3, 0.6, 0.9 and at 1.2 W/cm2 (all P < 0.05). CONCLUSION: Increasing
      intensities of CW-US exposure resulted in increased clot lysis of r-PA-treated
      blood clots, but decreased clot lysis of SK-treated clots.

PMID- 18727835
TI  - Knowledge transfer in Tehran University of Medical Sciences: an academic example
      of a developing country.
AB  - BACKGROUND: In the past two decades, scientific publications in Iran have
      considerably increased their medical science content, and the number of articles
      published in ISI journals has doubled between 1997 and 2001. The aim of the
      present study was to determine how frequently knowledge transfer strategies were
      applied in Tehran University of Medical Sciences (TUMS). We were also interested
      in studying the determining factors leading to the type of strategy selected.
      METHODOLOGY: All TUMS research projects that had received grants from inside and
      outside the university in 2004, and were completed by the end of 2006, were
      included in the study. In total, 301 projects were examined, and data on each of
      the projects were collected by the research team using a standardized
      questionnaire. The projects' principle investigators filled out a second
      questionnaire. In all, 208 questionnaires were collected. RESULTS: Researchers
      stated being more engaged in the passive strategies of knowledge transfer,
      especially those publishing in peer-reviewed journals. The mean score for the
      researchers' performance in passive and active strategies were 22% and 9% of the
      total score, respectively. Linear regression analysis showed that the passive
      strategy score decreased with the increase in the number of years working as a
      professional (p = 0.01) and personal interest as the only reason for choosing the
      research topic (p = 0.01). Regarding the active strategies of knowledge transfer,
      health system research studies significantly raised the score (p = 0.02) and
      'executive responsibility' significantly lowered it (p = 0.03). CONCLUSION: As a
      study carried out in a Middle Eastern developing country, we see that, like many
      other universities in the world, many academicians still do not give priority to
      active strategies of knowledge transfer. Therefore, if 'linking knowledge to
      action' is necessary, it may also be necessary to introduce considerable changes
      in academic procedures and encouragement policies (e.g., employment and promotion
      criteria of academic members).

PMID- 18727836
TI  - Primary carcinoid tumors of the liver.
AB  - BACKGROUND: Primary carcinoid tumors of the liver are uncommon and rarely
      symptomatic. The diagnosis of primary hepatic etiology requires rigorous workup
      and continued surveillance to exclude a missed primary. CASE PRESENTATION: We
      present a case of a 62-year-old female with a primary hepatic carcinoid tumor
      successfully resected, now with three years of disease-free follow-up. We present
      a review of the current literature regarding the diagnosis, pathology,
      management, and natural history of this disease entity. CONCLUSION: Primary
      carcinoid tumors of the liver are rare, therefore classifying their nature as
      primary hepatic in nature requires extensive workup and prolonged follow-up. All
      neuroendocrine tumors have an inherent malignant potential that must be
      recognized. Management remains surgical resection, with several alternative
      options available for non-resectable tumors and severe symptoms. The risk of
      recurrence of primary hepatic carcinoid tumors after resection remains unknown.

PMID- 18727837
TI  - Bioelectrical impedance phase angle as a prognostic indicator in breast cancer.
AB  - BACKGROUND: Bioelectrical impedance analysis (BIA) is an easy-to-use, non
      invasive, and reproducible technique to evaluate changes in body composition and
      nutritional status. Phase angle, determined by bioelectrical impedance analysis
      (BIA), detects changes in tissue electrical properties and has been hypothesized
      to be a marker of malnutrition. Since malnutrition can be found in patients with
      breast cancer, we investigated the prognostic role of phase angle in breast
      cancer. METHODS: We evaluated a case series of 259 histologically confirmed
      breast cancer patients treated at Cancer Treatment Centers of America. Kaplan
      Meier method was used to calculate survival. Cox proportional hazard models were
      constructed to evaluate the prognostic effect of phase angle independent of stage
      at diagnosis and prior treatment history. Survival was calculated as the time
      interval between the date of first patient visit to the hospital and the date of
      death from any cause or date of last contact/last known to be alive. RESULTS: Of
      259 patients, 81 were newly diagnosed at our hospital while 178 had received
      prior treatment elsewhere. 56 had stage I disease at diagnosis, 110 had stage II,
      46 had stage III and 34 had stage IV. The median age at diagnosis was 49 years
      (range 25-74 years). The median phase angle score was 5.6 (range = 1.5-8.9).
      Patients with phase angle < or = 5.6 had a median survival of 23.1 months (95%
      CI: 14.2 to 31.9; n = 129), while those > 5.6 had 49.9 months (95% CI: 35.6 to
      77.8; n = 130); the difference being statistically significant (p = 0.031).
      Multivariate Cox modeling, after adjusting for stage at diagnosis and prior
      treatment history found that every one unit increase in phase angle score was
      associated with a relative risk of 0.82 (95% CI: 0.68 to 0.99, P = 0.041). Stage
      at diagnosis (p = 0.006) and prior treatment history (p = 0.001) were also
      predictive of survival independent of each other and phase angle. CONCLUSION:
      This study demonstrates that BIA-derived phase angle is an independent prognostic
      indicator in patients with breast cancer. Nutritional interventions targeted at
      improving phase angle could potentially lead to an improved survival in patients
      with breast cancer.

PMID- 18727840
TI  - Cerebrospinal fluid markers in Creutzfeldt-Jakob disease.
AB  - BACKGROUND: The objective was to assess the utility of total tau protein (tTau),
      the ratio of (tTau)/181 phosphorylated tau protein (P-Tau) and 14-3-3 protein, as
      diagnostic markers in cerebrospinal fluid (CSF) for Creutzfeldt-Jakob disease
      (CJD). METHODS: CSF samples received from Norwegian hospitals between August 2005
      and August 2007 were retrospectively selected from consecutive patients with tTau
      values > 1200 ng/L (n = 38). The samples from patients clinically diagnosed with
      CJD (n = 12) were compared to those from patients with other degenerative
      neurological diseases: Alzheimer's/vascular dementia (AD/VaD, n = 21), other
      neurological diseases (OND, n = 5). Total Tau, P-Tau, and beta-Amyloid (Abeta42)
      were measured with commercial kits. Additionally, 14-3-3 protein was measured
      semi-quantitatively by immunoblot. RESULTS: The minimum cut-off limits for
      diagnosis of CJD were chosen from the test results. For tTau the lower limit was
      fixed at 3000 ng/L, for the tTau/P-Tau ratio it was 60, and for 14-3-3 protein it
      was 0.75 arbitrary units. For tTau and tTau/P-Tau ratio, all but three CJD
      patients had levels above the minimum, whereas almost all of the other patients
      were below. For the 14-3-3 protein, two CJD patients were below the minimum and
      five were above. Only one of the other patients was higher than the limit. The
      sensitivities, specificities and diagnostic efficiencies were: tTau 75%, 92%, and
      87%; tTau/P-Tau 75%, 96%, and 89%; and 14-3-3 protein 80%, 96%, and 91%.
      CONCLUSION: The results suggest that 14-3-3 protein may be the better marker for
      CJD, tTau/P-Tau ratio and tTau are also efficient markers, but showed slightly
      inferior diagnostic properties in this study, with tTau/P-Tau marginally better
      than tTau.

PMID- 18727838
TI  - Alignment of protein structures in the presence of domain motions.
AB  - BACKGROUND: Structural alignment is an important step in protein comparison. Well
      established methods exist for solving this problem under the assumption that the
      structures under comparison are considered as rigid bodies. However, proteins are
      flexible entities often undergoing movements that alter the positions of domains
      or subdomains with respect to each other. Such movements can impede the
      identification of structural equivalences when rigid aligners are used. RESULTS:
      We introduce a new method called RAPIDO (Rapid Alignment of Proteins in terms of
      Domains) for the three-dimensional alignment of protein structures in the
      presence of conformational changes. The flexible aligner is coupled to a genetic
      algorithm for the identification of structurally conserved regions. RAPIDO is
      capable of aligning protein structures in the presence of large conformational
      changes. Structurally conserved regions are reliably detected even if they are
      discontinuous in sequence but continuous in space and can be used for
      superpositions revealing subtle differences. CONCLUSION: RAPIDO is more sensitive
      than other flexible aligners when applied to cases of closely homologues proteins
      undergoing large conformational changes. When applied to a set of kinase
      structures it is able to detect similarities that are missed by other alignment
      algorithms. The algorithm is sufficiently fast to be applied to the comparison of
      large sets of protein structures.

PMID- 18727839
TI  - Expression and regulation of neurotrophins in the nondegenerate and degenerate
      human intervertebral disc.
AB  - INTRODUCTION: The neurotrophins nerve growth factor (NGF) and brain-derived
      neurotrophic factor (BDNF) have been identified in the human intervertebral disc
      (IVD) and have been implicated in the mechanisms associated with nerve ingrowth
      and nociception in degeneration of the IVD. The aim of the current study was to
      investigate an association between neurotrophin expression in the IVD and the
      severity of disc degeneration, including the effect of disc-related
      proinflammatory cytokines on neurotrophin and neuropeptide expression in cells
      derived from the human IVD. METHODS: Immunohistochemical analysis was performed
      to examine the expression of NGF, BDNF and their high-affinity receptors Trk-A
      and Trk-B in human IVD samples, divided into three categories: non-degenerate,
      moderate degeneration and severe degeneration. In order to study the effect of
      disc-related cytokines on neurotrophin/neuropeptide gene expression, nucleus
      pulposus cells derived from non-degenerate and degenerate IVD samples were seeded
      in alginate and were stimulated with either IL-1beta or TNFalpha for 48 hours.
      RNA was extracted, cDNA was synthesised and quantitative real-time PCR was
      performed to examine the expression of NGF, BDNF and substance P. RESULTS:
      Immunohistochemistry showed expression of NGF and BDNF in the native chondrocyte
      like cells in all regions of the IVD and in all grades of degeneration.
      Interestingly only BDNF significantly increased with the severity of degeneration
      (P < 0.05). Similar expression was observed for Trk-A and Trk-B, although no
      association with disease severity was demonstrated. In cultured human nucleus
      pulposus cells, stimulation with IL-1beta led to significant increases in NGF and
      BDNF gene expression (P < 0.05). Treatment with TNFalpha was associated with an
      upregulation of substance P expression only. CONCLUSION: Our findings show that
      both the annulus fibrosus and nucleus pulposus cells of the IVD express the
      neurotrophins NGF and BDNF, factors that may influence and enhance innervation
      and pain in the degenerate IVD. Expression of Trk-A and Trk-B by cells of the
      nondegenerate and degenerate IVD suggests an autocrine role for neurotrophins in
      regulation of disc cell biology. Furthermore, modulation of neurotrophin
      expression by IL-1beta and modulation of substance P expression by TNFalpha,
      coupled with their increased expression in the degenerate IVD, highlights novel
      roles for these cytokines in regulating nerve ingrowth in the degenerate IVD and
      associated back pain.

PMID- 18727841
TI  - Follicular development induced by recombinant luteinizing hormone (LH) and
      follicle-stimulating hormone (FSH) in anovulatory women with LH and FSH
      deficiency: evidence of a threshold effect.
AB  - OBJECTIVE: To assess the requirement for luteinizing hormone (LH) in women
      deficient in LH and follicle-stimulating hormone (FSH). RESEARCH DESIGN AND
      METHODS: A prospective, randomized, parallel-group, multicentre study was carried
      out in tertiary care and academic medical centres. Women with anovulatory
      amenorrhoea > or = 1 year, serum oestradiol (E(2)) < 60 pg/mL (< 220 pmol/L) and
      low normal serum gonadotrophins were randomized in cycle A to a fixed daily dose
      of recombinant human (r-h) FSH (150 IU) and r-hLH 0, 25, 75 or 225 IU. Cycles B
      and C were not randomized. MAIN OUTCOME MEASURES: Follicular development,
      ovulation and luteinization. RESULTS: In cycle A, follicular development was
      achieved by 63.6% (7/11), 100% (9/9), 72.7% (8/11) and 66.7% (6/9) of patients
      who received r-hFSH and r-hLH 0, 25, 75 or 225 IU/day, respectively (p = not
      significant). Among patients with basal serum LH of < 1.2 IU/L, a dose-response
      relationship of r-hLH to follicular development was observed (p = 0.039).
      Fourteen of 34 patients (41.2%) wishing to conceive became pregnant. Among
      patients with hypogonadotrophic hypogonadism (HH) treated with r-hFSH alone, a
      transition from LH dependence to independence was observed between basal LH
      values of > or = 1.2 IU/L and < or = 1.6 IU/L. The r-hLH was well tolerated and
      no serious adverse events occurred during treatment. The most common treatment
      related events were related to the reproductive system and the gastrointestinal
      tract. CONCLUSIONS: Recombinant human LH provides a safe treatment option for
      women with HH. This small study also provided evidence suggestive of an LH
      threshold: follicular development was suboptimal when less than 75 IU/day r-hLH
      was administered.

PMID- 18727843
TI  - Unexplained chronic fatigue and core conflictual relationship themes: A study in
      a chronically fatigued population.
AB  - OBJECTIVE: Unexplained fatigue syndromes are multidimensional phenomena that
      involve a constellation of symptoms. This paper explores whether typical
      relationship patterns are associated with self-reported and clinically rated
      fatigue symptoms in chronically fatigued patients. METHOD: Relationship patterns
      were assessed by means of the core conflictual relationship theme (CCRT) method.
      This method examines transference patterns, and was applied to interview data
      collected from chronically fatigued patients (N=30). Chronic fatigue was assessed
      by means of a self-report questionnaire and was also rated clinically. RESULTS:
      Both self-reported and clinically rated fatigue correlated with relationship
      themes. The intensity of fatigue related to the perception of others as not
      respecting and as negatively interfering. The typical reaction of the self to
      relationships consists of feeling disrespected, anger, passivity, and reduced
      feelings of self-consistency. CONCLUSION: Patients' perception of interpersonal
      relationships as distressing may be pivotal in understanding these results.
      Implications for clinical intervention and future research are indicated.

PMID- 18727842
TI  - The effect of a nicotine patch on cigarette craving over the course of the day:
      results from two randomized clinical trials.
AB  - OBJECTIVES: The objective of this analysis was to assess the efficacy of a 21
      mg/24-h nicotine patch for the reduction of craving throughout the waking day,
      compared both to placebo, and to a 15 mg/16-h patch differing pharmacokinetic
      profile over the day. The primary end-point was craving during the evening hours,
      because previous research suggested that smoking relapse was particularly likely
      at that time. RESEARCH DESIGN AND METHODS: Data were drawn from two similar
      randomized clinical trials among nicotine-dependent smokers who were quitting
      smoking: Study 1 compared the 21 mg/24-h patch to a placebo patch, while Study 2
      compared the 21 mg/24-h patch to a 15 mg/16-h nicotine patch. In both studies,
      subjects (Study 1: n = 102; Study 2: n = 244) were prompted by an electronic
      diary to rate their craving multiple times per day during a 1 week baseline
      period, and for up to 2 weeks after quitting. For analysis, the day was divided
      into five blocks: morning (up to 10:59 a.m.), mid-day (11:00 a.m.-1:59 p.m.),
      afternoon (2:00 p.m.-4:59 p.m.), evening (5:00 p.m.-8:59 p.m.), and late night
      (9:00 p.m. onwards). The individual craving ratings were divided into three
      intervals based on time since quitting: Days 1-3, 4-7, and 8-14. RESULTS: The 21
      mg/24-h nicotine patch resulted in significantly lower craving during all post
      quit intervals, at each time of day, both compared to placebo (Study 1), and
      compared to the 15 mg/16-h nicotine patch (Study 2). Study 2 saw a significant
      treatment by interval interaction: in later time intervals, the difference in
      craving experience between 24- and 16-h patch conditions shrunk--while remaining
      significantly different--as overall levels of craving experienced by subjects in
      the two groups dropped. Adverse events reported in both studies tended to be mild
      and transient, consistent with the well characterized adverse event profile of
      nicotine patches. CONCLUSIONS: Study 1 demonstrated that a 21 mg/24-h patch was
      effective in reducing craving throughout the day, including the evening period
      when relapse risk is heightened. A further study comparing the 21 mg/24-h patch
      to a 15 mg/16-h nicotine patch found that craving was significantly lower at all
      times of day for smokers using the 21 mg/24-h patch. The studies were limited in
      that craving was only monitored for the first 2 weeks of quitting (when craving
      is most prominent), and cannot elucidate the impact of patch use on craving
      outside of this time. Also, there was substantial attrition of the sample over
      time, partly due to relapse in all conditions.

PMID- 18727844
TI  - Psychiatric morbidity and treatment pathway outcomes of patients presenting to
      specialist NHS psychodynamic psychotherapy services: results from a multi-centre
      study.
AB  - OBJECTIVE: Little is known about socio-demographic, diagnostic, and clinical
      characteristics of patients referred for assessment to psychodynamic
      psychotherapy services. The aim of this study was to remedy this by prospectively
      collecting comprehensive and systematic demographic and clinical information on a
      large number of patients referred to NHS psychodynamic psychotherapy services.
      DESIGN: Fourteen psychotherapy services operating within a National Health
      Service joined the study and contributed data for 1,136 patients referred from
      primary and secondary care clinics. METHOD: Patients were assessed using
      questionnaires and self-rated measures, which included the clinician-based
      version of the diagnostic form of the Millon clinical multi-axial inventory-III
      revised edition (MCMI-III-R), the brief symptom inventory (BSI), the inventory of
      interpersonal problems (IIP), and the clinical outcome in routine evaluation
      (CORE). The pathway from assessment through to treatment and variables associated
      with treatment uptake and exclusion are described and examined. RESULTS: Most
      patients were in the moderate to severe range of psychiatric severity at the time
      of presentation. Ninety-five percent met clinically based criteria for a
      psychiatric disorder (mostly anxiety and mood disorders) and/or personality
      disorder. Although the majority of patients were found suitable for treatment
      (N=935, 82%), analysis of uptake showed relatively high rates of treatment
      rejection by patients and treatment drop-out. Partial outcome data at 6-month
      follow-up after intake into treatment revealed significant change but modest
      effect size (d=0.35). CONCLUSION: Systematic collection of baseline and outcome
      data would provide a national database of the performance of psychotherapy
      services that would be invaluable in facilitating comparative studies.

PMID- 18727845
TI  - Longitudinal assessment of anxiety, depression, and fatigue in people with
      multiple sclerosis.
AB  - OBJECTIVES: No longitudinal studies have concurrently evaluated predictors of
      anxiety, depression, and fatigue in people with multiple sclerosis (PwMS). This
      study determined factors that best predicted anxiety, depression, and fatigue in
      MS patients from a large pool of disease, cognitive, life-event stressor (LES),
      psychosocial, life-style, and demographic factors. DESIGN: A 2-year prospective
      longitudinal study evaluated predictors of psychological distress and fatigue in
      PwMS. METHODS: One hundred and one consecutive participants with MS were
      recruited from two MS clinics in Sydney, Australia. LES, anxiety, depression, and
      fatigue were assessed at baseline and at 3-monthly intervals for 2-years.
      Disease, cognitive, demographic, psychosocial, and life-style factors were
      assessed at baseline. Patient-reported relapses were recorded and corroborated by
      neurologists or evaluated against accepted relapse criteria. RESULTS: Depression
      strongly predicted anxiety and fatigue, and anxiety and fatigue strongly
      predicted later depression. Psychological distress (i.e. anxiety, depression) was
      also predicted by a combination of unhealthy behaviours (e.g. drug use, smoking,
      no exercise, or relaxation) and psychological factors (e.g. low optimism,
      avoidance coping), similar to the results of community-based studies. However,
      state-anxiety and fatigue were also predicted by immunotherapy status, and
      fatigue was also predicted by LES and demographics. CONCLUSIONS: These results
      suggest that similar factors might underpin psychological distress and fatigue in
      MS patients and community-well samples, although MS treatment factors may also be
      important. These results might assist clinicians in determining which MS patients
      are at greatest risk of developing anxiety, depression, or fatigue.

PMID- 18727846
TI  - Growth and nutritional status of children with homozygous sickle cell disease.
AB  - BACKGROUND: Poor growth and under-nutrition are common in children with sickle
      cell disease (SCD). This review summarises evidence of nutritional status in
      children with SCD in relation to anthropometric status, disease severity, body
      composition, energy metabolism, micronutrient deficiency and endocrine
      dysfunction. METHODS: A literature search was conducted on the Medline/PUBMED,
      SCOPUS, SciELO and LILACS databases to July 2007 using the keywords sickle cell
      combined with nutrition, anthropometry, growth, height and weight, body mass
      index, and specific named micronutrients. RESULTS: Forty-six studies (26 cross
      sectional and 20 longitudinal) were included in the final anthropometric
      analysis. Fourteen of the longitudinal studies were conducted in North America,
      the Caribbean or Europe, representing 78.8% (2086/2645) of patients. Most studies
      were observational with wide variations in sample size and selection of reference
      growth data, which limited comparability. There was a paucity of studies from
      Africa and the Arabian Peninsula, highlighting a large knowledge gap for low
      resource settings. There was a consistent pattern of growth failure among
      affected children from all geographic areas, with good evidence linking growth
      failure to endocrine dysfunction, metabolic derangement and specific nutrient
      deficiencies. CONCLUSIONS: The monitoring of growth and nutritional status in
      children with SCD is an essential requirement for comprehensive care,
      facilitating early diagnosis of growth failure and nutritional intervention.
      Randomised controlled trials are necessary to assess the potential benefits of
      nutritional interventions in relation to growth, nutritional status and the
      pathophysiology of the disease.

PMID- 18727847
TI  - Delivery care utilisation and care-seeking in the neonatal period: a population
      based study in Vietnam.
AB  - BACKGROUND: If millions of neonatal deaths each year are to be prevented, one
      crucial component that must be improved is adequate care-seeking behaviour and
      effective use of existing health care systems. We have investigated these factors
      in relation to delivery and the neonatal period in a province in Northern
      Vietnam, a setting currently in socio-economic transition. METHODS: Information
      on births and neonatal deaths between January and December 2005 in Quang Ninh
      province was collected. Narratives of the neonatal deaths were gathered and
      information about care-seeking in relation to delivery and illness was extracted.
      This information was then compared with the time and place of delivery and death.
      RESULTS: We registered 17,519 births and 284 neonatal deaths occurring between
      January and December 2005. The neonatal mortality rate varied from 7.5/1000 to
      38/1000, depending on the place of delivery. A quarter of the neonatal deaths had
      no contact with the health-care system at the time of death. Neonatal death
      within 24 hours of birth was more likely when the mother did not seek care at the
      time of delivery, or did so at the lowest level of the system (chi2=35.5,
      p<0.001). Mothers of ethnic minorities were more likely to exhibit this care
      seeking behaviour at delivery. CONCLUSION: Further improvement in neonatal
      survival can be achieved by changes in health system utilisation that aim to
      secure safe delivery for pregnant women. More efforts at local level are needed
      to encourage adequate care-seeking.

PMID- 18727848
TI  - Meconium-stained amniotic fluid and meconium aspiration syndrome: a prospective
      study.
AB  - BACKGROUND: The incidence of meconium aspiration syndrome (MAS), associated
      perinatal factors, morbidity and deaths varies widely. This study aimed to assess
      the perinatal attributes and morbidity associated with MAS. METHODS: Over a 2
      year period, all neonates born through meconium-stained amniotic fluid (MSAF)
      were observed for respiratory distress (RD). Birth details, chest radiograph
      (CXR) and clinical course were documented. Neonates with consistent CXR findings
      whose RD could not otherwise be explained were defined as MAS. RESULTS: Of 409
      neonates born through MSAF, meconium was thick in 196 (47.9%). Fifty-five (13.4%)
      had RD and 45 (11.3%) were consistent with MAS. Six (1.5%) neonates died. Mean
      (SD) birthweight and gestation of MAS infants were 2721.9 (510.2) g and 38.67
      (1.09) weeks, respectively. About one-third were of low birthweight and 28 were
      born by caesarean section. On univariate analysis, caesarean delivery, meconium
      in the trachea and thick meconium were the significant perinatal factors for the
      development of MAS. On multiple regression analysis, thick meconium was the only
      independent factor for MAS (OR 7.08, 95% CI 3.08-16.27, p<0.001). An Apgar score
      of <or=6 and blood gas abnormalities were found in 44.4% and 48.9%, respectively.
      Air leak syndrome was observed in 12 (26.7%), persistent pulmonary hypertension
      in seven and severe asphyxia and late sepsis in two each. Thirteen (28.9%)
      required mechanical ventilation and six (13.3%) died. CONCLUSION: MAS occurred in
      11.3% of neonates born through MSAF. Thick meconium was found to be an important
      causative factor. Nearly one-third of infants with MAS required mechanical
      ventilation and 13.3% died.

PMID- 18727849
TI  - Hazards of pentazocine for neonatal analgesia: a single-centre experience over 10
      years.
AB  - BACKGROUND: In developing countries, neonatal analgesia for surgical procedures
      is a major challenge where postoperative care is inadequate. AIM: To report
      experience of pentazocine for neonatal surgery in a Nigerian tertiary hospital.
      METHODS: A retrospective study of surgical neonates who received pentazocine at
      the University of Benin Teaching Hospital in Benin City between January 1998 and
      December 2007. RESULTS: During the period, 2590 paediatric operations were
      performed including 368 (14.2%) neonates, 49 (13.3%) of whom had pentazocine. The
      other neonates received a variety of analgesics. Of 56 neonates who developed
      respiratory depression, 40 (71.4%) had pentazocine (p<0.0001). Fifteen (30.6%)
      neonates aged between 9 hours and 28 days [mean (SD) 12 (1.2) days] died between
      1 and 36 hours following 8-hourly administration of 0.5 mg/kg pentazocine. In
      older children who had pentazocine, over-sedation was also a problem but there
      were no deaths. Deaths in neonates were mainly owing to persistent respiratory
      depression which was compounded by the unavailability of a paediatric ventilator.
      However, many neonates responded to naloxone. All neonates who died had an
      autopsy and no lesion was found which could have compromised respiratory
      function. CONCLUSION: The use of pentazocine in neonates was associated with high
      morbidity and mortality. Caution is required when using pentazocine for neonatal
      analgesia where post-operative respiratory support is insufficient.

PMID- 18727850
TI  - Bacterial meningitis following introduction of Hib conjugate vaccine in northern
      Uganda.
AB  - BACKGROUND: St Mary's Hospital, Lacor is in Gulu district in northern Uganda.
      Owing to conflict and insurgency, the majority of the hospital population live in
      internally displaced people's camps. There is ongoing public health surveillance
      of paediatric bacterial meningitis by the hospital. Before the introduction of
      Haemophilus influenza type b (Hib) conjugate vaccine in June 2002, Hib was the
      leading cause of bacterial meningitis in the area. METHODS: All patients with
      suspected bacterial meningitis between April 2003 and August 2006 were recruited.
      Meningitis was confirmed by isolation of bacteria. RESULTS: During the study
      period, 4986 cases of suspected bacterial meningitis were identified, 395 of whom
      had purulent cerebrospinal fluid (CSF). A culture was obtained from 259 (65%):
      Streptococcus pneumoniae 132 (51%), H. influenzae 22 (8.5%), salmonella spp 85
      (32.8%), Neisseria meningitidis 9 (3.5%) and others 11 (4.2%). Over the
      surveillance period, there was a remarkable decline in the prevalence of H.
      influenza meningitis to only three cases or fewer per year compared with 42 in
      2001. The minimum incidence of Streptococcus pneumoniae meningitis among children
      under 5 years of age was 33.7/100,000 of population and it was more prevalent
      during the dry season. The minimum incidence of non-typhoidal salmonella spp
      meningitis was 22.7/100,000, making it the second most common cause of paediatric
      bacterial meningitis with a case fatality rate of 18.2%. CONCLUSION: Hib
      conjugate vaccine delivered through the national immunisation programme is very
      effective in reducing Hib meningitis in children under 5 years of age. Continued
      laboratory-based surveillance of bacterial meningitis in Africa is needed to
      assess the effectiveness of vaccination programmes and detect other vaccine
      preventable pathogens.

PMID- 18727852
TI  - Dilated cardiomyopathy secondary to nutritional rickets.
AB  - Two 9-month-old breastfed infants presented with congestive heart failure
      secondary to dilated cardiomyopathy. No underlying aetiology was found, except
      for the presence of advanced rickets. Following treatment with vitamin D and
      calcium supplements, both infants quickly recovered normal myocardial function.

PMID- 18727851
TI  - Monitoring psychomotor development in a resource-limited setting: an evaluation
      of the Kilifi Developmental Inventory.
AB  - BACKGROUND: Modifications made to the Kilifi Developmental Checklist and the
      psychometric characteristics of the new measure (The Kilifi Developmental
      Inventory) which assess the psychomotor functioning of children aged 6-35 months
      are described. METHODS: Two groups of community children (319 rural and 104 urban
      dwellers) and nine children with neurodevelopmental disorders were recruited for
      a cross-sectional study. RESULTS: In both a rural and urban reference population,
      the inventory showed excellent internal consistency, interobserver agreement,
      test-retest reliability and sensitivity to maturational changes. Children with
      neurodevelopmental impairment and those who were underweight had significantly
      lower scores than the community sample, attesting to the sensitivity of the
      measure. Mothers found the assessment procedures acceptable and informative.
      CONCLUSIONS: The Kilifi Developmental Inventory is a culturally appropriate
      measure that can be used to monitor and describe the development of at-risk
      children in resource-limited settings in Kenya.

PMID- 18727853
TI  - Cryptococcal meningitis in an immunocompetent adolescent.
AB  - Cryptococcus neoformans is a rare cause of meningitis especially in
      immunocompetent children. Cryptococcal meningitis in a healthy Chinese adolescent
      is reported. She responded well to treatment with intravenous amphotericin and
      oral flucytosine.

PMID- 18727854
TI  - Fetal ascites owing to congenital cytomegalovirus: response to ganciclovir.
AB  - A term newborn with severe congenital cytomegalovirus (CMV) infection is
      described. Fetal ascites was detected at 28 weeks gestation, and at birth there
      was tense ascites. There was intra-uterine growth retardation, microcephaly,
      chorioretinitis, jaundice, purpura and pneumonitis. Computed tomographic scan of
      the brain showed ventriculomegaly with periventricular calcifications. Serology
      was positive for cytomegalovirus-specific immunoglobulin M, and cytomegalovirus
      DNA was detected in the ascitic fluid and urine by nested polymerase chain
      reaction. He received 6 weeks of treatment with ganciclovir. Ascites resolved
      spontaneously and liver function tests became normal. Although there was a good
      clinical response to ganciclovir therapy without any side-effects, on follow-up
      the infant had global developmental delay and bilateral sensorineural deafness.

PMID- 18727855
TI  - Behaviour of human mesenchymal stem cells on a polyelectrolyte-modified HEMA
      hydrogel for silk-based ligament tissue engineering.
AB  - The aim of this study was to design a functional bio-engineered material to be
      used as scaffold for autologous mesenchymal stem cells in ligament tissue
      engineering. Polyelectrolyte modified HEMA hydrogel (HEMA-co-METAC), applied as
      coating on silk fibroin fibres, has been formulated in order to take advantage of
      the biocompatibility of the polyelectrolyte by increasing its mechanical
      properties with silk fibres. Human bone marrow mesenchymal stem cells behaviour
      on such reinforced polyelectrolyte has been studied by evaluating cell
      morphology, cell number, attachment, spreading and proliferation together with
      collagen matrix production and its mRNA expression. Silk fibroin fibres matrices
      with HEMA-co-METAC coating exhibited acceptable mechanical behaviour compared to
      the natural ligament, good human mesenchymal stem cell adhesion and with mRNA
      expression studies higher levels of collagen types I and III expression when
      compared to control cells on polystyrene. These data indicate high expression of
      mRNA for proteins responsible for the functional characteristics of the ligaments
      and suggest a potential for use of this biomaterial in ligament tissue
      engineering applications.

PMID- 18727856
TI  - Variation of the mechanical properties of PMMA to suit osteoporotic cancellous
      bone.
AB  - Poly(methyl methacrylate) (PMMA) is by far the most frequently used bone
      substitute material for vertebroplasty. However, there are serious complications,
      such as cement leakage and an increased fracture rate of the adjacent vertebral
      bodies. The latter may be related to the mechanical properties of the augmented
      segment within the osteoporotic spine. A possible counter-measure is prophylactic
      augmentation at additional levels, but this aggravates the risk for the patient.
      Introduction of pores is a possible method to reduce the inherent high stiffness
      of PMMA. This study investigates the effect of porosity on the mechanical
      properties of PMMA bone cement. Different fractions of a highly viscous liquid
      were mixed into the PMMA during preparation. An open-porous material with
      adjustable mechanical properties resulted after removal of the aqueous phase.
      Different radiopacifiers were admixed to investigate their suitability for
      vertebroplasty. The final material was characterized mechanically by compressive
      testing, microscopically and radiologically. In addition, the monomer release
      subsequent to hardening was measured by means of gas chromatography. The Young's
      modulus in compression could be varied between 2800 +/- 70 MPa and 120 +/- 150
      MPa, and the compression ultimate strength between 170 +/- 5 MPa and 8 +/- 9 MPa
      for aqueous fractions ranging between 0 and 50% of volume. Only a slight decrease
      of the Young's modulus and small changes of ultimate strength were found when the
      mixing time was increased. An organic hydrophilic and lipophilic radiopacifier
      led to a higher Young's modulus of the porous material; however, the ultimate
      strength was not significantly affected by adding different radiopacifiers to the
      porous cement. The radiopacity was lost after washing the aqueous phase out of
      the pores. No separation occurred between the aqueous and the PMMA phase during
      injection into an open porous ceramic material. The monomer released was found to
      increase for increasing aqueous fractions, but remained comparable in magnitude
      to standard PMMA. This study demonstrates that a conventional PMMA can be
      modified to obtain a range of mechanical properties, including those of
      osteoporotic bone.

PMID- 18727857
TI  - Furan-functionalized co-polymers for targeted drug delivery: characterization,
      self-assembly and drug encapsulation.
AB  - We have previously reported furan-maleimide Diels-Alder chemistry as a new
      methodology to couple maleimide-modified antibodies on furan-functionalized
      polymeric carriers in the preparation of immuno-nanoparticles for targeted drug
      delivery. In this report, we focus on the characterization, self-assembly
      behavior and drug encapsulation of two types of furan-functionalized co-polymers:
      poly(2-methyl, 2-carboxytrimethylene carbonate-co-D,L-lactide)-furan (poly(TMCC
      co-LA)-furan) and poly(2-methyl, 2-carboxytrimethylene carbonate-co-D,L-lactide)
      graft-poly(ethylene glycol)-furan (poly(TMCC-co-LA)-g-PEG-furan). The co-polymers
      were synthesized by modifying the carboxylic acid groups on the poly(TMCC-co-LA)
      backbone by either furfurylamine or PEG-furan to generate either linear co
      polymers of poly(TMCC-co-LA)-furan with furan pendant groups or graft co-polymers
      of poly(TMCC-co-LA)-g-PEG-furan with furan-terminated PEG grafts, respectively.
      Using a membrane dialysis method, both of the co-polymers were self-assembled
      into nanoparticles in aqueous environments driven by the hydrophobic association
      among polymer chains. The hydrophobic domains in the nanoparticles were confirmed
      by the incorporation of pyrene molecules and the critical aggregation
      concentrations were determined to be approximately 5 x 10(-5) mM for poly(TMCC-co
      LA)-furan and 2 x 10(-4) mM for poly(TMCC-co-LA)-g-PEG-furan. By the addition of
      borate buffer in the organic solvent used to dissolve the co-polymers in the
      dialysis procedure, we were able to control the size of the nanoparticles: 54-169
      nm for poly(TMCC-co-LA)-furan and 28-283 nm for poly(TMCC-co-LA)-g-PEG-furan.
      This unique feature can be explained by the ionization of carboxylic acid groups
      along the co-polymer backbone. A hydrophobic anticancer drug, doxorubicin (DOX),
      was encapsulated within the nanoparticles, with the larger size nanoparticles
      incorporating greater amounts of DOX. Combining the strategy of antibody-mediated
      targeting, these self-assembled nanoparticles have potential as efficient anti
      cancer drug carriers.

PMID- 18727858
TI  - Carcinogen adsorbent prepared from DNA complex by gamma-ray irradiation.
AB  - The effects of gamma-ray irradiation on aqueous solutions of chub mackerel
      chromatin, salmon milt DNA with CoCl(2), mixtures of DNA with Type A gelatin,
      bovine serum albumin (BSA), CM-chitosan, carboxymethyl cellulose (CMC) and
      Catinal (hydroxyethyl-cellulose, O-[2-hydroxy-3-(trimethyl ammonio)-propyl],
      chloride) and DNA in the presence of polyfunctional monomers with the aim to
      insolubilize DNA for preparing a novel carcinogen adsorbent have been studied.
      Among those, precipitates or inhomogeneous gel consisting of cross-linked DNA
      were prepared from the samples of aqueous DNA in the presence of CoCl(2) at low
      irradiation dose, around 10 Gy, and bulk homogeneous gels were successfully
      prepared from aqueous mixtures of DNA with gelatin, BSA, CMC and Catinal in a
      limited range of irradiation doses. Gel fraction and swelling ratio of the gels
      were measured. Adsorption of a carcinogen, acridine orange, was also examined for
      the gels. From the experimental results, the optimum conditions for preparing
      insolubilized homogeneous DNA gels were determined.

PMID- 18727859
TI  - PLGA microsphere/calcium phosphate cement composites for tissue engineering: in
      vitro release and degradation characteristics.
AB  - Bone cements with biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres
      have already been proven to provide a macroporous calcium phosphate cement (CPC)
      during in situ microsphere degradation. Furthermore, in vitro/in vivo release
      studies with these PLGA microsphere/CPC composites (PLGA/CPCs) showed a sustained
      release of osteo-inductive growth factor when drug was distributed inside/onto
      the microspheres. The goal of this study was to elucidate the mechanism behind
      drug release from PLGA/CPC. For this, in vitro release and degradation
      characteristics of a low-molecular-weight PLGA/CPC (M(w) = 5 kg/mol) were
      determined using bovine serum albumin (BSA) as a model protein. Two loading
      mechanisms were applied; BSA was either adsorbed onto the microspheres or
      incorporated inside the microspheres during double-emulsion. BSA release from
      PLGA microspheres and CPC was also measured and used as reference. Results show
      fast degrading polymer microspheres which produced a macroporous scaffold within
      4 weeks, but also showed a concomitant release of acidic degradation products.
      BSA release from the PLGA/CPC was similar to the CPC samples and showed a pattern
      consisting of a small initial release, followed by a period of almost no
      sustained release. Separate PLGA microspheres exhibited a high burst release and
      release efficiency that was higher with the adsorbed samples. Combining
      degradation and release data we can conclude that for the PLGA/CPC samples BSA re
      adsorbed to the cement surface after being released from the microspheres, which
      was mediated by the pH decrease during microsphere degradation.

PMID- 18727860
TI  - Poly(hydroxyethyl methacrylate)-based co-polymeric hydrogels for transdermal
      delivery of salbutamol sulphate.
AB  - Various co-polymeric hydrogels for transdermal delivery of salbutamol sulphate
      were synthesized using 2-hydroxyethyl methacrylate (HEMA), methacrylic acid (MAA)
      and N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) in the presence of
      ammonium persulphate (APS) and N,N,N',N'-tetramethylethylenediamine (TEMED) as
      redox free radical initiator and ethyleneglycol dimethacrylate (EGDMA) as a cross
      linker. The synthesized co-polymeric hydrogels were characterized using FT-IR
      spectral studies and swelling studies. It was observed that percentage swelling
      of co-polymeric hydrogel increased with the increasing concentration of DMAPMA
      and methacrylic acid. Salbutamol sulphate, a well-known vasodilator, was labeled
      with (99m)Tc(technetium) and loaded on circular discs of various hydrogels. In
      vitro permeation of radiolabelled salbutamol sulphate was carried out using a
      Franz diffusion cell in phosphate-buffered saline (PBS, pH 7.4) as dissolution
      medium through mice skin. It was observed that drug release from the co-polymeric
      hydrogel carriers increased on increasing the amount of DMAPMA in the polymeric
      carriers, while it decreased on increasing the amount of MAA content. The local
      toxicity studies of DMAPMA-containing hydrogel patches were carried out in
      rabbits. Drug-loaded patches applied on rabbit skin showed no toxicity, even
      after 1 week of studies.

PMID- 18727861
TI  - Heparin-modified dendrimer cross-linked collagen matrices for the delivery of
      basic fibroblast growth factor (FGF-2).
AB  - Tissue integration between a tissue-engineered corneal equivalent and the host
      eye is of critical importance in ensuring long-term implant success. A novel
      dendrimer cross-linked collagen scaffold has previously shown good corneal
      epithelial cell compatibility in vitro particularly when the highly functional
      dendrimer cross-linkers were functionalized to introduce additional biological
      groups. Herein we investigated heparinization of these materials and their
      potential to facilitate the delivery of basic fibroblast growth factor (FGF-2) in
      an active form, ultimately for use as a corneal tissue scaffold. Collagen gels
      cross-linked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride
      (EDC) and N-hydroxysuccinimide (NHS) chemistry, and varying amounts of
      polypropyleneimine octaamine generation 2 (G2) dendimer and heparin were
      synthesized. Swelling studies and differential scanning calorimetry
      characterization indicated higher gel stability with the introduction of
      dendrimer cross-linking, which was not compromised by heparin integration.
      Dendrimer cross-linked gels with or without heparin gave multiple denaturation
      peaks, as did the heparinized EDC gels. This is thought to be the result of the
      heterogeneous cross-linking possible between collagen, the dendrimer and heparin.
      Release of FGF-2 from collagen gels showed typical first-order kinetics, with an
      initial burst followed by a prolonged gradual release. Heparinized dendrimer
      cross-linked gels released approx. 40% of the growth factor over a 2-week period,
      with significance maintenance of growth factor activity. Incorporation of heparin
      resulted in somewhat prolonged release from these systems.

PMID- 18727862
TI  - Fibrin promotes proliferation and matrix production of intervertebral disc cells
      cultured in three-dimensional poly(lactic-co-glycolic acid) scaffold.
AB  - Previously, we have proven that fibrin and poly(lactic-co-glycolic acid) (PLGA)
      scaffolds facilitate cell proliferation, matrix production and early
      chondrogenesis of rabbit articular chondrocytes in in vitro and in vivo
      experiments. In this study, we evaluated the potential of fibrin/PLGA scaffold
      for intervertebral disc (IVD) tissue engineering using annulus fibrosus (AF) and
      nucleus pulposus (NP) cells in relation to potential clinical application. PLGA
      scaffolds were soaked in cells-fibrin suspension and polymerized by dropping
      thrombin-sodium chloride (CaCl(2)) solution. A PLGA-cell complex without fibrin
      was used as control. Higher cellular proliferation activity was observed in
      fibrin/PLGA-seeded AF and NP cells at each time point of 3, 7, 14 and 7 days
      using the MTT assay. After 3 weeks in vitro incubation, fibrin/PLGA exhibited a
      firmer gross morphology than PLGA groups. A significant cartilaginous tissue
      formation was observed in fibrin/PLGA, as proven by the development of cells
      cluster of various sizes and three-dimensional (3D) cartilaginous
      histoarchitecture and the presence of proteoglycan-rich matrix and
      glycosaminoglycan (GAG). The sGAG production measured by 1,9-dimethylmethylene
      blue (DMMB) assay revealed greater sGAG production in fibrin/PLGA than PLGA
      group. Immunohistochemical analyses showed expressions of collagen type II,
      aggrecan core protein and collagen type I genes throughout in vitro culture in
      both fibrin/PLGA and PLGA. In conclusion, fibrin promotes cell proliferation,
      stable in vitro tissue morphology, superior cartilaginous tissue formation and
      sGAG production of AF and NP cells cultured in PLGA scaffold. The 3D porous PLGA
      scaffold-cell complexes using fibrin can provide a vehicle for delivery of cells
      to regenerate tissue-engineered IVD tissue.

PMID- 18727863
TI  - A hybrid thermo-sensitive chitosan gel for sustained release of Meloxicam.
AB  - The purpose of this work was to develop a multi-phase gel system for sustained
      release drug delivery. A thermo-sensitive hydrogel composed of chitosan and
      glycerol was prepared, and then an o/w emulsion was introduced to the thermo
      sensitive gel in order to modulate the gelation behavior. Meloxicam was chosen as
      a model drug in this study and its release profile was investigated. This study
      revealed that the factors such as pH, chitosan molecular mass and glycerol
      concentration could significantly influence the gel formation. Chitosan with a
      molecular mass of 950 kDa and glycerol proportion ranging from 30 to 60% can form
      a pH-dependent thermo-sensitive gel system. Both the chitosan-glycerol gel and
      chitosan-glycerol-emulsion gel systems were applied in delivering drugs. The drug
      release from the two gels was both in Higuchi mode. Higuchi moduli were 3.04 x
      10(-3) mg x h((1/2)) in the chitosan-glycerol-emulsion gel and 1.28 mg x h((1/2))
      in the chitosan- glycerol gel. The former was significantly slower in sustained
      release. The in vivo investigation on the chitosan-glycerol gel indicated that
      the gel may be useful in sustained drug release in situ. Thermosensitive
      hydrogels composed of chitosan and glycerol were well formed and could act as a
      sustained release drug carrier in the work, it showed that this hybrid thermo
      sensitive hydrogel system may be a promising sustained release drug carrier.

PMID- 18727864
TI  - A nanosized, thermo-sensitive drug carrier: self-assembled Fe(3)O(4)-OA-g-P(OA-co
      NIPAAm) magnetomicelles.
AB  - Novel thermo-sensitive magnetomicelles that consist of a magnetic core, Fe(3)O(4)
      oleic acid (Fe(3)O(4)-OA), and an amphiphilic surface layer of thermo-sensitive
      poly(oleic acid-co-N-isopropylacrylamide) P(OA-co-NIPAAm) co-polymer were
      prepared. Fe(3)O(4) magnetic cores functionalized with double bonds of oleic acid
      were prepared by suspension-oxidation reaction. Subsequently, by the co
      polymerization of hydrophilic NIPAAm, hydrophobic OA and the Fe(3)O(4)-OA
      magnetic core, the thermo-sensitive amphiphilic polymers (P(OA-co-NIPAAm)) were
      grafted to obtain Fe(3)O(4)-OA-g-P(OA-co-NIPAAm) nanoparticles. The surface
      polymeric layer of Fe(3)O(4)-OA-g-P(OA-co-NIPAAm) nanoparticles would self
      assemble in aqueous media to form a micellar structure attributed to the
      amphiphilic P(OA-co-NIPAAm) polymers. The model drug, prednisone acetate, was
      loaded in the magnetomicelles and in vitro release behavior of loaded drug in
      magnetomicelles was further investigated, which showed a thermo-sensitive release
      behavior due to the thermo-sensitive structural changes of the micellar surface
      layer.

PMID- 18727865
TI  - [Effect of curcumin on the expression of collagen type I protein and transforming
      growth factor-beta1 mRNA in pulmonary fibrosis rats].
AB  - OBJECTIVE: To study the effects of curcumin on the expressions of collagen type I
      protein and transforming growth factor-beta1 mRNA in lung tissues of rats with
      pulmonary fibrosis. METHODS: 96 male SD rats were randomly divided into four
      groups with 24 rats in each group: the normal control group, the model group, the
      prednisone treated group, and the curcumin treated group. Pulmonary fibrosis was
      induced by intra-bronchial injection of bleomycin A5. From the 15(th) day after
      bleomycin administration, rats in the prednisone treated group and the curcumin
      treated group were given prednisone (5 mg/kg) or curcumin (300 mg/kg)
      respectively once daily by intragastric administration. In the same way, rats in
      the normal control group and the model group were given 1% Sodium Carboxymethyl
      Cellulose (10 ml/kg) once daily. The histological changes of lung tissue were
      evaluated by Haematoxylin-eosin (HE) and Masson's trichrome. The rats were
      randomly sacrificed on the 21(st), 28(th), 42(nd) and 56(th) day after bleomycin
      administration. The type I collagen expression was analyzed by
      immunohistochemistry. The transforming growth factor-beta(1) (TGF-beta(1)) mRNA
      expression of lung was detected by the semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: Pulmonary fibrosis in the curcumin
      treated group was significantly reduced as compared with the model group and the
      prednisone treated group on the 42(nd) and 56(th) day (P < 0.05). The expression
      of type I collagen protein in the curcumin treated group was significantly
      decreased than that in the model group and the prednisone treated group on the
      28(th), 42(nd) and 56(th) day after bleomycin administration (P < 0.05). The TGF
      beta(1) mRNA expression in the curcumin treated group was 0.61 +/- 0.09 and 0.48
      +/- 0.16 respectively on the 21(st) and 28(th) day after bleomycin administration
      (P < 0.05). It was significantly decreased than that in the model group on the
      21(st), 28(th) day after bleomycin administration and lower as compared with the
      prednisone treated group on the 21(st) day (P < 0.05). CONCLUSION: Curcumin could
      suppress BLM-induced pulmonary fibrosis in rats at the fibrosing stage, with the
      possible mechanism of inhibiting the synthesis and deposition of type I collagen
      protein and depressing the overexpression of TGF-beta(1) mRNA. The therapeutic
      effect of curcumin on pulmonary fibrosis is better than prednisone.

PMID- 18727866
TI  - [Comparative research on evaluation methods of quality of injury surveillance
      based emergency room].
AB  - OBJECTIVE: To evaluate the quality of injury surveillance based-emergency room
      and find a simple, convenient and practical comprehensive evaluation method.
      METHODS: Seventeen indexes were extracted from influencing factors questionnaires
      of injury surveillance which was collected in the emergency room of a general
      hospital from July 2006 to March 2007, evaluated by TOPSIS (Technique for order
      preference by similarity to ideal solution) and GRA (grey relational analysis),
      given the order and compared with the practical results from injury surveillance
      reporting cards and emergency department logs. RESULTS: The correlation
      coefficient between GRA and practical results was 0.750 (P = 0.020). The
      correlation coefficient between TOPSIS and practical results was 0.167 (P =
      0.668). The correlation coefficient between GRA and TOPSIS was 0.083 (P = 0.831).
      CONCLUSION: GRA is more suitable than TOPSIS for evaluation of the quality of
      injury surveillance based-emergency room, and it can be used to evaluate the
      quality of injury surveillance, and provide timely and effective basis for injury
      prevention strategies.

PMID- 18727867
TI  - [Measurement and analysis of human head-face dimensions].
AB  - OBJECTIVE: To probe into the physical changes on the head and face of Chinese
      adults, find the representative indexes and provide references for head-face
      products design especially in the field of labor protection. METHODS: The ISO7250
      1996 and GB/T5703-99 Basic Human Body Measurements for Technological Design was
      used. Twenty items of head-face referential parameters and 4 items of body
      indexes (height, weight, waist circumference and buttock circumference) were
      measured by using sliding caliper, spreading caliper and pupillometer. The
      populations were sampled by age, gender and region and their influences on the
      head and face dimensions were statistically analyzed. By studying the
      relationship between these parameters with correlation and cluster analysis, the
      representative indexes of head and face dimensions were concluded. RESULTS: 3000
      objectives (2026 men and 974 women) were involved in this survey. The results
      enunciated that the values of the items in male were larger than those in female.
      For example, the mean values of face length, face width, jaw width, lip length
      and nose protrusion were 117.0, 147.6, 118.5, 51.7, 18.7 mm for male and 109.7,
      140.1, 114.5, 49.3, 17.7 mm for female. The regional disparity and obesity were
      significant factors. The sizes of head and face of north-eastern population were
      significantly bigger than those of south-western population except of maximum
      length of head, the length of lip and face configuration length. The sizes of
      head and face of obesity population were significantly bigger than those of non
      obesity population (P < 0.01). By the cluster analysis, five representative
      indexes (face length, face width, jaw width, lip length and nose protrusion) were
      obtained. Further correction analysis suggested that these indexes could well
      represent the head-face dimensions. CONCLUSION: The influence of gender, region
      and obesity on the head-face dimensions is significant. The age is not a
      significant influential factor. Five representative indexes (face length, face
      width, jaw width, lip length and nose protrusion) are obtained to provide
      foundation in the standard design of head-face products.

PMID- 18727868
TI  - [Regulation role of superoxide dismutase coenzyme on Fas/FasL signal transduction
      and apoptosis in alveolar macrophages of pneumoconiosis patients].
AB  - OBJECTIVE: To explore the role of superoxide dismutase (SOD) coenzyme in
      regulation of Fas/FasL signal transduction and apoptosis of alveolar macrophages
      in pneumoconiosis patients. METHODS: 50 male and Han nationality cases, including
      the dust exposed workers, Phase I, II pneumoconiosis patients confirmed by local
      pneumoconiosis diagnosis group according to GBZ 70 - 2002 diagnosis standard, who
      underwent whole lung lavage treatment were chosen as subjects. Their alveolar
      macrophages (AMs) were collected and purified. The cells were divided into three
      groups: the untreated group, the Fas/FasL group and the SOD group. 5 x 10(6)
      purified AMs were added into incubating bottles containing DMEM for 2 hours for
      purifying, added with SOD coenzyme and other block reagents separately, and then
      incubated for 24 hours in CO(2) incubation. The cells were harvested and lysed.
      Western-blot were used to analyze the expressions of Fas, FasL, Caspases-8 and
      Caspases-3. Software of Quantity One 7.0 was used to analyze the relative
      quantity of Fas, FasL, Caspase-8 and Caspase-3. TUNEL and DNA fragment analysis
      were used to analyze AMs apoptosis. RESULTS: The apoptosis index in SOD coenzyme
      group (9.50 +/- 2.76)% and Fas/FasL group (14.01 +/- 2.56)% was significantly
      lower than that of in untreated group (19.18 +/- 2.83)% (P < 0.05). The
      catachrestic DNA ladder appeared in untreated group, was looming in Fas/FasL
      group, and was not found in the SOD group. The expressions of Fas, FasL, Caspase
      8 and Caspase-3 of phase I and II in SOD group were higher than in the other two
      groups (P < 0.05). There was no significant difference in the expression of Fas,
      FasL, Caspase-8 and Caspase-3 among different phases of pneumoconiosis (P >
      0.05). CONCLUSION: SOD coenzyme can effectively regulate Fas/FasL signal
      transduction and block AMs apoptosis.

PMID- 18727869
TI  - [DMF-induced adult hepatocyte apoptosis and its effects on expression of Bcl-2,
      Bax and Caspase-3].
AB  - OBJECTIVE: To investigate the apoptosis-inducing effect of DMF on the human liver
      cells (HL-7702) in vitro. METHODS: Liver cells were exposed to different
      concentrations of DMF (0, 50, 100, 150, 200 mmol/L) for 12 hours. Apoptotic rate,
      the expression of Bax, Bcl-2 and Caspase-3 in liver cells were measured by FCM
      and western blotting respectively. RESULTS: The increase in apoptotic rate of
      hepatocytes in concentration-manner was shown after DMF treatment for 12 h. After
      treatment the expression of Bcl-2 was decreased steadily and lower than the
      control group (P < 0.01), the expression of Bax showed no significant difference
      among the groups of different dosage by one-factor analysis of variance (P >
      0.05), as the increase of the dosage of DMF. The ratio of Bcl-2/Bax dropped with
      the dosage of DMF increasing, and the ratio in 200 mmol/L of DMF was
      significantly lower than that of the control (P < 0.01). The new lands of
      procaspase-3 in 150, 200 mmol/L were observed, which demonstrated that there was
      active caspase-3. CONCLUSION: DMF can induce apoptosis of cultured adult normal
      hepatocytes in vitro, and the mechanism might be related to the decrease of Bcl
      2/Bax and the cleavage of Caspase-3.

PMID- 18727870
TI  - [Method for concentration determination of mineral-oil fog in the air of
      workplace].
AB  - OBJECTIVE: To study the method of concentration determination of mineral-oil fog
      in the air of workplace. METHODS: Four filter films such as synthetic fabric
      filter film, beta glass fiber filter film, chronic filter paper and microporous
      film were used in this study. Two kinds of dust samplers were used to collect the
      sample, one sampling at fast flow rate in a short time and the other sampling at
      slow flow rate with long duration. Subsequently, the filter membrane was weighed
      with electronic analytical balance. According to sampling efficiency and
      incremental size, the adsorbent ability of four different filter membranes was
      compared. RESULTS: When the flow rate was between 10 approximately 20 L/min and
      the sampling time was between 10 approximately 15 min, the average sampling
      efficiency of synthetic fabric filter film was 95.61% and the increased weight
      ranged from 0.87 to 2.60 mg. When the flow rate was between 10 approximately 20
      L/min and sampling time was between 10 approximately 15 min, the average sampling
      efficiency of beta glass fiber filter film was 97.57% and the increased weight
      was 0.75 approximately 2.47 mg. When the flow rate was between 5 approximately 10
      L/min and the sampling time between 10 approximately 20 min, the average sampling
      efficiency of chronic filter paper and microporous film was 48.94% and 63.15%,
      respectively and the increased weight was 0.75 approximately 2.15 mg and 0.23
      approximately 0.85 mg, respectively. When the flow rate was 3.5 L/min and the
      sampling time was between 100 approximately 166 min, the average sampling
      efficiency of filter film were 94.44% and 93.45%, respectively and the average
      increased weight was 1.28 mg for beta glass fiber filter film and 0.78 mg for
      beta glass fiber filter film and synthetic fabric synthetic fabric filter film.
      The average sampling efficiency of chronic filter paper and microporous film were
      37.65% and 88.21%, respectively. The average increased weight was 4.30 mg and
      1.23 mg, respectively. CONCLUSION: Sampling with synthetic fabric filter film and
      beta glass fiber filter film is credible, accurate, simple and feasible for
      determination of the concentration of mineral-oil fog in workplaces.

PMID- 18727871
TI  - [Effects of butyl benzyl phthalate on neurobehavioral development of rats].
AB  - OBJECTIVE: To study the effects of butyl benzyl phthalate on neurobehavioral
      development of rats. METHODS: Levels of 0 (control), 0.05%, 0.25%, and 0.75%
      butyl benzyl phthalate (BBP) was given in the diet from 4 weeks of age of female
      F0 generation to 6 weeks of age of F1 generation in Wistar rats, including the
      period of the female F0 generation's mating, gestation and lactation and the F1
      generation's growth and development. Selected parameters of neurobehavioral
      development were observed in F1 generation. RESULTS: (1)For the male F(1)
      generation, surface righting at postnatal (PND) 4 th day was significantly
      delayed in the low-dose group (P < 0.05) (scoring: 56 vs 61), cliff avoidance at
      PND 7 was significantly depressed in the high-dose group (P < 0.05) (scoring:
      41), air righting at PND 14 was significantly depressed in all treatment groups
      (P < 0.05). In open field test, low- and high-dose groups moved more than control
      group (P < 0.05). In Morris water maze test, the escape latency was significantly
      delayed in the low-dose group at the 5th day of the 5 days' place navigation task
      (P < 0.05). (2) For the female F1 generation, there were no differences among
      groups in any parameter in the experiment (P > 0.05). CONCLUSION: BBP may affect
      the neurobehavioral development only in male rats in the F1 generation.

PMID- 18727872
TI  - [Observation of biological surveillance indexes of coke oven workers].

PMID- 18727873
TI  - [DMF induced human liver cell DNA impairment effect].

PMID- 18727874
TI  - [Protection effect of genistein on mice with acute liver impairment].

PMID- 18727875
TI  - [Genotoxicity of volatile mixture in decorated rooms for mice].

PMID- 18727876
TI  - [CT manifestation of environmental asbestos pollution induced pleural plaques].

PMID- 18727877
TI  - [How to implement social responsibility of enterprises].

PMID- 18727878
TI  - [Accelerate action for global strategy aim of decent work].

PMID- 18727879
TI  - [Preliminary study on legislation of work injury insurance of farmer-workers].

PMID- 18727880
TI  - [Open a new era of guaranteeing and promoting overall health of laborers --
      introduction of WHA 60.26 resolution].

PMID- 18727881
TI  - [Primary occupational hygiene service in Bao An district of Shenzhen].

PMID- 18727882
TI  - [Solvent desorption gas phase chromatography for determination of alpha
      methylphenylene in air of work place].

PMID- 18727883
TI  - [ICP-AES method for determination of several hazardous elements in air].

PMID- 18727884
TI  - [Atomic fluorescence spectrometry for determination of Hg in blood and urine
      samples].

PMID- 18727885
TI  - [Sudden death from respiratory disease in sports].

PMID- 18727886
TI  - [Assessment of patient satisfaction and preferences with inhalers in asthma with
      the FSI-10 Questionnaire].
AB  - BACKGROUND AND OBJECTIVE: Lack of adherence to inhaled corticosteroid therapy is
      common in patients with asthma, and it has been suggested that allowing patients
      to choose their own inhalers would resolve this problem. The FSI-10 (Feeling of
      Satisfaction with Inhaler) is a self-completed questionnaire to assess patient
      opinions regarding ease or difficulty of use, portability, and usability of
      devices for delivery of inhaled corticosteroids. The aim of this study was to
      define the measurement properties of the FSI-10 questionnaire and to use this
      inventory to compare satisfaction and preferences of patients with asthma
      regarding 3 different devices for delivery of inhaled corticosteroids:
      Turbuhaler, Accuhaler, and Novolizer. PATIENTS AND METHODS: We performed a
      multicenter, prospective, observational study in 112 stable asthmatic patients
      (64 women; mean [SD] age, 37 [22] years) treated on a regular basis with inhaled
      corticosteroids. The use of the devices was explained to the patients and the
      order in which they should be used in each case was randomly assigned. The
      devices were used for 7-day periods and at the end of each the FSI-10
      questionnaire was completed for the device used. Once the protocol was completed,
      patients stated their preference for the different devices used. RESULTS: The FSI
      10 was easily understood and rapidly completed, and it exhibited acceptable
      measurement properties. Factor analysis showed that the measure was
      unidimensional. Although acceptance of all 3 devices assessed was reasonable, the
      FSI-10 questionnaire detected significant differences between them: Turbuhaler
      and Novolizer scored higher than Accuhaler on a number of questions. This
      preference is partly explained by Turbuhaler having been the device that was
      commonly used by the patients prior to the study. However, the highest scoring
      and most often preferred inhaler in patients under 16 years of age was the
      Novolizer, even though the Turbuhaler had also usually been used by those
      patients prior to the study. CONCLUSIONS: The FSI-10 is a useful instrument for
      assessing the degree of satisfaction of asthmatic patients regarding available
      inhalation devices. It is easy to understand and complete, and able to identify
      differences in patient satisfaction with the different inhalers.

PMID- 18727887
TI  - [Acute renal failure in lung transplantation: incidence, correlation with
      subsequent kidney disease, and prognostic value].
AB  - OBJECTIVE: We studied the incidence of postoperative renal failure and its
      association with mortality in lung transplant patients in our hospital classified
      according to the severity of renal failure in the immediate postoperative period,
      and at 30 days, 6 months, and 1 year after transplantation. MATERIAL AND METHODS:
      For the period March 1997 through January 2006, 144 lung transplants were
      performed in our hospital. Six patients were lost to follow-up. Patients were
      assigned to 1 of the 5 Chronic Kidney Disease (CKD) classes according to the
      glomerular filtration rate on admission to the intensive care unit, and at 1
      month, 6 months, and 12 months. Descriptive statistics were calculated for the
      sample. The relationship between the CKD classification and mortality was
      analyzed by calculating the odds ratio with a logistic regression model. The
      correlation between CKD classification on admission and at 1 month, 6 months, and
      1 year after transplantation was analyzed using the Spearman correlation
      coefficient. RESULTS: Of the 144 patients analyzed, 52 patients were in CKD class
      1, 63 in class 2, 19 in class 3, 2 in class 4, and 2 in class 5, according to the
      glomerular filtration rate. The correlation between mortality at 1 month and CKD
      classification on admission was not statistically significant (odds ratio, 1.11;
      95% confidence interval, 0.42-3.11; P=.82) among patients with normal kidney
      function (CKD class 1) and those with some degree of renal failure (CKD classes 2
      5). There was no correlation between CKD classification on admission and CKD
      classification at 1 month, 6 months, and 1 year although a significant positive
      correlation was found between CKD classification at 1 month and CKD classes at 6
      months and 1 year. CONCLUSIONS: We did not find any association between 1-month
      mortality and the degree of renal failure in the immediate postoperative period
      in lung transplant patients. There was a positive correlation between the degree
      of kidney failure at 1 month and that observed 6 and 12 months after the
      procedure.

PMID- 18727888
TI  - [Local anesthesia in arterial puncture: nurses' knowledge and attitudes].
AB  - OBJECTIVE: Local anesthesia is rarely used in arterial puncture, even though it
      is recommended. The aim of this study was to examine attitudes and beliefs among
      nurses and third-year undergraduate nursing students in hospital training
      regarding the use of local anesthesia when performing arterial puncture and to
      assess their knowledge of the technique. MATERIAL AND METHODS: Nurses and nursing
      students were issued a 15-item questionnaire consisting of 2 parts. The first
      part contained questions on the nurse's use of local anesthesia when extracting
      arterial blood for analysis and the second part involved questions regarding
      technical knowledge of this test. The results of nurses from the respiratory
      medicine department, nurses from the rest of the hospital, and nursing students
      were compared. RESULTS: The questionnaire was answered by the 131 the nurses
      surveyed. Valid questionnaires were returned by 17 of the 19 nursing students
      surveyed. Questionnaires returned by nurses from the respiratory medicine
      department (n=11) were separated from those returned by the rest of nurses. Local
      anesthesia was used routinely by 7 nurses (5%), of whom 3 (27%) belonged to the
      respiratory medicine department; local anesthesia was not used by any of the
      nursing students. The main reasons given by nurses for not using local anesthesia
      were lack of knowledge (54%), need to perform 2 punctures when anesthesia is used
      (11%), belief that the same amount of pain is caused with anesthesia (8%), and
      success on the first attempt at arterial puncture (7%). The main reason given by
      student nurses for not using local anesthesia was also lack of knowledge (53%),
      followed by the fact that it was not used by the nurses (24%). Most of those
      surveyed (63%) indicated a desire to receive anesthesia should they undergo
      arterial puncture. CONCLUSIONS: Local anesthesia is used very little in arterial
      puncture. Knowledge about how to perform arterial blood extraction for blood gas
      analysis is insufficient and needs to be improved among both nurses and nursing
      students. Nonetheless it is noteworthy that most of those surveyed indicated a
      preference for receiving local anesthesia if they were to undergo the procedure.
      These data should be taken into consideration when training nurses to perform
      arterial puncture.

PMID- 18727889
TI  - [Computed tomography-guided radiofrequency ablation of malignant lung lesions:
      early experience].
AB  - OBJECTIVE: To present our early experience in the treatment of primary malignant
      and metastatic lung lesions by radiofrequency ablation. PATIENTS AND METHODS:
      From August 2004 through January 2007 we treated 19 patients (in 26 procedures)
      with curative or palliative intent. None of the lesions was amenable to surgery
      and some had been treated previously. The procedure was performed in the
      radiology room under conscious sedation-analgesia administered by an
      anesthesiologist. Fourteen patients were treated for pulmonary lesions and 5 for
      metastatic lung disease in a context of controlled primary disease. Treatment was
      with curative intent in 15 cases and palliative in 4. RESULTS: The radiofrequency
      technique was applicable in 26 procedures and the mean follow-up was 8.68 months.
      The principal complications of radiofrequency treatment were pneumothorax in 4
      patients, requiring drainage in only 2 cases; pneumonitis in 4; self-limiting
      pulmonary hemorrhage in 1; and pleural effusion in 5. There were no procedure
      related deaths. Six patients died during the follow-up period. CONCLUSIONS: In
      our experience, radiofrequency offers a safe and minimally invasive option for
      the treatment of malignant lung lesions in appropriately selected, nonsurgical
      patients. Morbidity is low, and in combination with other treatments this
      technique opens up a wide range of possibilities still to be explored.

PMID- 18727890
TI  - [Sleep disorders in patients on a kidney transplant waiting list].
AB  - OBJECTIVE: To evaluate the prevalence of sleep disorders in patients awaiting
      kidney transplants compared to a control group. PATIENTS AND METHODS: We carried
      out an observational study of 23 patients on a kidney transplant waiting list in
      comparison with 20 healthy volunteers matched for age, sex, and body mass index
      (BMI). Overnight polysomnography was performed and a diagnosis of sleep apnea
      hypopnea syndrome (SAHS) established when the apnea-hypopnea index (AHI) was 10
      or higher. RESULTS: Eighty-two percent of the patients awaiting kidney
      transplants (16 men and 7 women with a mean [SD] age of 51 [15] years and a mean
      BMI of 25 [3.8] kg/m2) had some type of sleep disorder. The most frequent
      disorders were SAHS (48%) and insomnia and periodic limb movement disorder (30%).
      Patients showed poorer sleep efficiency compared to the control group (75.4% vs
      87.8%; P=.01) and a lower percentage of slow-wave and rapid eye movement sleep
      (24.5% vs 40%; P=.001). Those with sleep-disordered breathing had a higher AHI
      (17.7 vs 3.6; P=.001) and oxygen desaturation index (31.5 compared to 8.2;
      P=.001). CONCLUSIONS: Sleep disorders are common in patients awaiting kidney
      transplants. Such patients show reduced quantity and quality of sleep compared to
      controls and a significantly elevated number of respiratory events that may
      affect morbidity and mortality.

PMID- 18727892
TI  - [The halo sign in computed tomography images: differential diagnosis and
      correlation with pathology findings].
AB  - The halo sign is a circular area of ground-glass attenuation that is seen around
      pulmonary nodules at computed tomography (CT). Although the sign is most often an
      indication of pulmonary hemorrhage, it may also accompany other lesions
      associated with different disease processes. Examples are hemorrhagic nodules of
      infectious origin (mucormycosis, candidiasis, tuberculosis, viral pneumonia, and
      invasive aspergillosis--the last being the most common cause of the CT halo
      sign); hemorrhagic nodules of noninfectious origin (Wegener granulomatosis,
      Kaposi sarcoma, and hemorrhagic metastases); tumor cell infiltration
      (bronchioloalveolar carcinoma, lymphoma, and metastasis with intra-alveolar tumor
      growth); and nonhemorrhagic lesions (sarcoidosis and organizing pneumonia).
      Diagnosis must therefore be based on careful consideration of all the CT chest
      findings within the context of the patient's clinical state. The aim of this
      review was to describe and illustrate different disease processes that appear as
      a halo sign on CT scans, to analyze the value of this diagnostic tool, and to
      assess its correlation with pathology findings.

PMID- 18727894
TI  - [Etanercept as a possible trigger of fatal pulmonary fibrosis].
AB  - Pulmonary fibrosis can be caused by external agents, including certain drugs. For
      some time now, tumor necrosis factor antagonists such as etanercept have been
      used to treat certain autoimmune diseases. Fibrosis caused by medication responds
      to withdrawal of the drug and treatment with corticosteroids. Very rarely,
      fibrosis is irreversible. We present the case of a patient who developed
      pulmonary fibrosis after initiating treatment with etanercept. The clinical
      course was fulminant despite withdrawal of the drug and high doses of
      corticosteroids.

PMID- 18727895
TI  - [Biliothorax unrelated to fistula: a rare complication in gallbladder disease].

PMID- 18727896
TI  - [Pheochromocytoma as a cause of massive hemoptysis].

PMID- 18727897
TI  - Beyond the impact factory.

PMID- 18727898
TI  - Bacterial flagellar motor.

PMID- 18727899
TI  - Uniparental inheritance of organelle genes.

PMID- 18727900
TI  - Barotrauma is a significant cause of bat fatalities at wind turbines.

PMID- 18727901
TI  - Believing is seeing: expectations alter visual awareness.

PMID- 18727902
TI  - Neural basis for unique hues.

PMID- 18727903
TI  - Colour vision: the wonder of hue.
AB  - Understanding the brain requires a kind of thinking outside the main tradition of
      natural science: the biology has to be linked to something intangible, a private
      experience. Physiologists have recently recorded from neurons that promise to
      help make the link in the case of colour experience.

PMID- 18727904
TI  - Centrosomes: keeping tumors in check.
AB  - Centrosomal abnormalities have been observed in a wide range of tumors, but it is
      not clear whether these abnormalities alone can induce cancer formation or
      whether they are a consequence of cancer progression. Recent work in Drosophila
      suggests that centrosome defects in asymmetrically dividing cells can induce
      tumors at a higher frequency than other conditions known to cause genomic
      instability.

PMID- 18727905
TI  - Auditory neuroscience: sound segregation in the brainstem?
AB  - Separating a mixture of sounds into its constituent parts is a complex process
      likely to involve many processing stages. A new study suggests that the first
      steps in that process may occur already at the level of the first auditory
      processing centre in the brainstem.

PMID- 18727906
TI  - Developmental timing: let-7 function conserved through evolution.
AB  - Expression of the heterochronic microRNA let-7 is tightly correlated with the
      onset of adult development in many animals, suggesting that it functions as an
      evolutionarily conserved developmental timer. This hypothesis has now been
      confirmed by studies in Drosophila.

PMID- 18727907
TI  - Multisensory integration: a functional role for inter-area synchronization?
AB  - It has been suggested that synchronization of neural activity in distinct areas
      of the brain is important in the 'perceptual binding' of the various features
      relating to a specific object. A recent study has provided new evidence that
      inter-area synchronization is important in multisensory integration.

PMID- 18727908
TI  - HIV-1 infection: going nuclear with TNPO3/Transportin-SR2 and integrase.
AB  - Factors necessary for HIV-1 nuclear import have been sought for many years.
      Recent reports suggest that TNPO3/Transportin-SR2 binds to HIV-1 integrase and is
      required for HIV-1 infection of interphase cells.

PMID- 18727909
TI  - Vision: attention makes the cup flow over.
AB  - Scalp potentials are surprisingly informative about visual attention: a recent
      study that used them to record neural responses to up to four superimposed visual
      patterns simultaneously has now revealed the flow of attentional signals back to
      visual cortex.

PMID- 18727910
TI  - Intracellular transport: kinesins working together.
AB  - While most in vitro experiments with motor proteins focus on the behavior of
      individual motors, in cells most cargo are transported by multiple motors and
      even multiple classes of motor. How these motors cooperate and compete in
      transporting cargo is not clear. Recent experimental and theoretical work
      suggests that motors attached to a given cargo interact in both expected and
      unexpected ways.

PMID- 18727911
TI  - Candida biofilms: is adhesion sexy?
AB  - The development of Candida albicans biofilms requires two types of adhesion
      molecule - the Als proteins and Hwp1. Mutational analyses have recently revealed
      that these molecules play complementary roles, and their characteristics suggest
      that they may have evolved from primitive mating agglutinins.

PMID- 18727912
TI  - Different chain length specificity among three polyphosphate quantification
      methods.
AB  - Polyphosphate is ubiquitous among living organisms and has a variety of
      biochemical functions. Arbuscular mycorrhizal fungi have been known to accumulate
      polyphosphate as a key compound for their function. However, an enzymatic assay
      using polyphosphate kinase (PPK) reverse reaction, in which polyphosphate is
      converted to adenosine triphosphate (ATP) and quantified by luciferase assay,
      failed to detect accumulation of polyphosphate in some mycorrhizal root. When
      yeast exopolyphosphatase (PPX) was applied to these samples, a much higher
      polyphosphate level was detected than when the PPK assay was applied. Detailed
      analysis of substrate chain length specificity of these methods using
      polyphosphate chain length standards revealed that the PPX method was the most
      appropriate to detect short-chain polyphosphate. The average chain length of the
      shortest polyphosphate fraction that could be quantified with more than 50%
      efficiency was 3 for the PPX method and 38 for the PPK method. It was also
      suggested that the ratio of the PPK value to the PPX value may be useful as a
      simple and relative index to compare polyphosphate chain length distribution in
      different samples.

PMID- 18727913
TI  - 2-O-[2-(4,4'-dimethoxytrityloxyethyl)]-hydroxy acetaldehyde: a universal reagent
      for spectrophotometric estimation of polymer-supported functional groups.
AB  - A new universal reagent, 2-O-[2-(4,4'-dimethoxytrityloxyethyl)]-hydroxy
      acetaldehyde (DEA), has been synthesized and used for the estimation of surface
      bound aminoalkyl, aminooxyalkyl, hydrazinyl, and semicarbazide functions. The
      reaction completes in just 10 min in the case of aminoalkylated supports and 30
      min in hydrazinyl supports, whereas it takes approximately 60 min in both
      aminooxyalkylated and semicarbazide-modified polymer supports. DEA-treated
      supports, including glass slides and PP films on exposure to acid, liberates 4,4'
      dimethoxytrityl cation, which was measured spectrophotometrically to estimate
      these functionalities. The method estimates accessible functional groups, useful
      for calculating the quantity of the ligands to be immobilized.

PMID- 18727914
TI  - Regulation of the bHLH transcription factor E2A in epithelial cells by
      interaction with the Na/K-ATPase beta1 subunit.
AB  - The bHLH transcription factor E2A controls proliferation and differentiation in
      many cell types including kidney epithelial cells. To identify regulatory binding
      partners of E2A in the kidney, a yeast two-hybrid assay with a human adult kidney
      cDNA library was performed. Results demonstrated E2A interactions with other HLH
      proteins including Id1-3 and Pod1 and the Na/K-ATPase beta1 subunit. The
      specificity of beta1 subunit binding was confirmed by co-immunoprecipitation of
      E2A and beta1 subunit deletion constructs in HEK cells demonstrating E2A binding
      to the cytoplasmic tail of the beta1 subunit. Immunofluorescence and Western
      analysis of HEK cells co-transfected with GFP-beta1 subunit and E2A demonstrated
      E2A membrane binding and increased beta1 subunit membrane localization. Increased
      beta1 subunit expression resulted in decreased nuclear E2A expression and protein
      half-life and reduced E2A induced gene expression. These results suggest that E2A
      and Na/K-ATPase beta1 subunit expression in epithelial cells are regulated by
      interactions between these proteins.

PMID- 18727915
TI  - NS5ATP9 gene regulated by NF-kappaB signal pathway.
AB  - NS5ATP9 was previously identified as p15 PAF [proliferating cell nuclear antigen
      (PCNA)-associated factor] to bind with PCNA. We earlier identified the promoter
      region of NS5ATP9 and found NS5ATP9 is a NS5A up-regulation gene. However little
      is known about how it is regulated. To investigate the gene regulation of
      NS5ATP9, we screened NS5ATP9 promoter binding proteins using phage display and
      verified by electrophoretic mobility shift assay (EMSA). We found that the
      nuclear protein rhNF-kappaB (p50) could bind to the NS5ATP9 promoter and the
      binding region contained within a 156 bp (nucleotides -5 to -161bp) immediately
      upstream of the transcription initiation site. Our results suggest that NF-kappaB
      could participate in the regulation of NS5ATP9 gene expression in carcinogenesis.

PMID- 18727916
TI  - Age-dependent high-density clustering of GM1 ganglioside at presynaptic neuritic
      terminals promotes amyloid beta-protein fibrillogenesis.
AB  - The deposition of amyloid beta-protein (Abeta) is an invariable feature of
      Alzheimer's disease (AD); however, the biological mechanism underlying Abeta
      assembly into fibrils in the brain remains unclear. Here, we show that a high
      density cluster of GM1 ganglioside (GM1), which was detected by the specific
      binding of a novel peptide (p3), appeared selectively on synaptosomes prepared
      from aged mouse brains. Notably, the synaptosomes bearing the high-density GM1
      cluster showed extraordinary potency to induce Abeta assembly, which was
      suppressed by an antibody specific to GM1-bound Abeta, an endogenous seed for AD
      amyloid. Together with evidence that Abeta deposition starts at presynaptic
      terminals in the AD brain and that GM1 levels significantly increase in amyloid
      positive synaptosomes prepared from the AD brain, our results suggest that the
      age-dependent high-density GM1 clustering at presynaptic neuritic terminals is a
      critical step for Abeta deposition in AD.

PMID- 18727917
TI  - Tamoxifen does not inhibit the swell activated chloride channel in human
      neutrophils during the respiratory burst.
AB  - Effective functioning of neutrophils relies upon electron translocation through
      the NADPH oxidase (NOX). The electron current generated (I(e)) by the neutrophil
      NADPH oxidase is electrogenic and rapidly depolarises the membrane potential in
      activated human neutrophils. Swelling activated chloride channels have been
      demonstrated in part to counteract the depolarisation generated by the NADPH
      oxidase I(e). In the present study, the effects of inhibitors of swell activated
      chloride channels on ROS production and on the swelling activated chloride
      conductance was investigated in activated human neutrophils. Tamoxifen (10
      microM), a specific inhibitor for swell activated chloride channels in
      neutrophils, completely inhibited both the PMA and FMLP stimulated respiratory
      burst. This inhibition of the neutrophil respiratory burst was not due to the
      blocking effect of tamoxifen on the swelling activated chloride conductance in
      these cells. These results demonstrate that a tamoxifen insensitive swell
      activated chloride channel has important significance during the neutrophil
      respiratory burst.

PMID- 18727918
TI  - An N-terminal 78 amino acid truncation of REIC/Dkk-3 effectively induces
      apoptosis.
AB  - Overexpression of REIC/Dkk-3 (a tumor suppressor gene) induces cancer cell
      apoptosis through endoplasmic reticulum (ER) stress. Therefore, the
      identification of the portion of REIC/Dkk-3 that causes ER stress may be
      essential for the development of cancer treatment based on REIC/Dkk-3. Here, we
      made several truncated forms of REIC/Dkk-3 and investigated their therapeutic
      potentials against prostate cancer. Among three truncated forms, a variant
      comprising the N-terminal 78 amino acid region of REIC/Dkk-3 ((1-78)REIC/Dkk-3)
      most strongly induced ER stress and apoptosis in human prostate cancer cells
      (PC3). For in vivo gene expression, we coupled a biodegradable polymer with naked
      DNA, which attained robust trans-gene expression in PC3-derived subcutaneous
      tumor. In therapeutic experiments, we demonstrated that multiple direct
      injections of polymer-conjugated (1-78)REIC/Dkk-3 plasmid provoke ER stress and
      significantly reduced the subcutaneous tumor volume compared with the control
      group. We suggest this non-viral strategy may be an effective alternative to
      viral gene therapy.

PMID- 18727919
TI  - The effect of high intensity focused ultrasound treatment on metastases in a
      murine melanoma model.
AB  - This study aims to assess the risk of high intensity focused ultrasound (HIFU)
      therapy on the incidence of distant metastases and to investigate its association
      with HIFU-elicited anti-tumor immunity in a murine melanoma (B16-F10) model.
      Tumor-bearing legs were amputated immediately after or 2 days following HIFU
      treatment to differentiate the contribution of the elicited anti-tumor immunity.
      In mice undergoing amputation immediately after mechanical, thermal, or no HIFU
      treatment, metastasis rates were comparable (18.8%, 13.3%, and 12.5%). In
      contrast, with a 2-day delay in amputation, the corresponding metastasis rates
      were 6.7%, 11.8%, and 40%, respectively. Animal survival rate was higher and CTL
      activity was enhanced in the HIFU treatment groups. Altogether, our results
      suggest that HIFU treatment does not increase the risk of distant metastasis.
      Instead, HIFU treatment can elicit an anti-tumor immune response that may be
      harnessed to improve the overall effectiveness and quality of cancer therapy.

PMID- 18727920
TI  - Some effects of the venom of the Chilean spider Latrodectus mactans on endogenous
      ion-currents of Xenopus laevis oocytes.
AB  - A study was made of the effects of the venom of the Chilean spider Latrodectus
      mactans on endogenous ion-currents of Xenopus laevis oocytes. 1 microg/ml of the
      venom made the resting plasma membrane potential more negative in cells voltage
      clamped at -60 mV. The effect was potentially due to the closure of one or
      several conductances that were investigated further. Thus, we determined the
      effects of the venom on the following endogenous ionic-currents: (a) voltage
      activated potassium currents, (b) voltage-activated chloride-currents, and (c)
      calcium-dependent chloride-currents (Tout). The results suggest that the venom
      exerts its action mainly on a transient outward potassium-current that is
      probably mediated by a Kv channel homologous to shaker. Consistent with the
      electrophysiological evidence we detected the expression of the mRNA coding for
      xKv1.1 in the oocytes.

PMID- 18727921
TI  - Oxidative stress induced lipid accumulation via SREBP1c activation in HepG2
      cells.
AB  - SREBP1c (sterol regulatory element-binding protein 1c) is a metabolic-syndrome
      associated transcription factor that controls fatty acid biosynthesis under
      glucose/insulin stimulation. Oxidative stress increases lipid accumulation, which
      promotes the generation of reactive oxygen species (ROS). However, we know little
      about the role of oxidative stress in fatty acid biosynthesis. To clarify the
      action of oxidative stress in lipid accumulation via SREBP1c, we examined SREBP1c
      activity in H2O2-treated mammalian cells. We introduced a luciferase reporter
      plasmid carrying the SREBP1c-binding site into HepG2 or COS-7 cells. With
      increasing H2O2 dose, SREBP1c transcriptional activity increased in HepG2 cells
      but declined in COS-7 cells. RT-PCR analysis revealed that mRNA expression of
      SREBP1c gene or of SREBP1c-regulated genes rose H2O2 dose-dependently in HepG2
      cells but dropped in COS-7 cells. Lipid accumulation and levels of the nuclear
      form of SREBP1c increased in H2O2-stimulated HepG2 cells. ROS may stimulate lipid
      accumulation in HepG2 cells via SREBP1c activation.

PMID- 18727922
TI  - CYP3A53A allele is associated with reduced lowering-lipid response to
      atorvastatin in individuals with hypercholesterolemia.
AB  - BACKGROUND: The cytochrome P450 isoenzyme 3A5 (CYP3A5) has an important role on
      biotransformation of xenobiotics. CYP3A5 SNPs have been associated with
      variations on enzyme activity that can modify the metabolism of several drugs.
      METHODS: In order to evaluate the influence of CYP3A5 variants on response to
      lowering-cholesterol drugs, 139 individuals with hypercholesterolemia were
      selected. After a wash-out period of 4 weeks, individuals were treated with
      atorvastatin (10 mg/day/4 weeks). Genomic DNA was extracted by a salting-out
      procedure. CYP3A5*3C, CYP3A5*6 and CYP3A5*1D were analyzed by PCR-RFLP and DNA
      sequencing. RESULTS: >Frequencies of the CYP3A5*3C and CYP3A5*1D alleles were
      lower in individuals of African descent (*3C: 47.8% and *1D: 55.2%) than in non
      Africans (*3C: 84.9% and *1D 84.8%, p<0.01). Non-Africans carrying *3A allele
      (*3C and *1D combined alleles) had lower total and LDL-cholesterol response to
      atorvastatin than non-*3A allele carriers (p<0.05). CONCLUSION: CYP3A5*3A allele
      is associated with reduced cholesterol-lowering response to atorvastatin in non
      African individuals.

PMID- 18727923
TI  - Differentially expressed serum haptoglobin alpha chain isoforms with potential
      application for diagnosis of head and neck cancer.
AB  - BACKGROUND: The discovery of molecular biomarkers is crucial to the diagnosis of
      head and neck squamous cell cancer (HNSCC). METHODS: Proteins from pre-surgery
      serum samples of patients with HNSCC and healthy individuals were analyzed by 2
      dimensional gel electrophoresis (2-DE) using a 17 cm-long immobilized pH gradient
      gel strip (large gel). The differentially expressed protein spots were detected
      by statistical analysis. Because 2 haptoglobin (Hp) alpha chains were found to be
      differentially expressed, the genotypic distribution of Hp alpha chains in
      patients and healthy individuals was assayed by polymerase chain reaction. The
      protein expression levels of Hp alpha chains in individuals carrying different Hp
      alleles were analyzed by 2-DE with a small gel. RESULTS: Two isoforms of
      haptoglobin alpha2 chain (Hp alpha2) in patients' sera were found from 2-DE
      analysis to be up-regulated, while the isoforms of haptoglobin alpha1 chain (Hp
      alpha1) were significantly down-regulated. Apolipoprotein AII and 2 isoforms of
      apolipoprotein CII were also differentially expressed in the sera of patients
      with HNSCC. The Hp alpha2 chain was significantly up-regulated in the patients
      carrying at least one haptoglobin 2 allele, according to the spot intensities
      from scanned images of small-gel 2-DE. CONCLUSIONS: The expression pattern of
      seven differentially expressed polypeptides and the up-regulation of Hp alpha2 in
      individuals with the Hp 2 allele are potential biomarkers.

PMID- 18727924
TI  - Variation in osteoarthritis biomarkers from activity not food consumption.
AB  - BACKGROUND: To optimize sampling and to understand sources of variation in
      biomarkers for osteoarthritis (OA), we evaluated variation due to activity and
      food consumption. METHODS: Twenty participants, with radiographic knee OA,
      provided serial serum and urine samples at 4 time points: before arising in the
      morning; after 1 h of light activity; 1 h after eating breakfast; and in the
      evening. Five serum (s) and 2 urinary (u) analytes were measured: hyaluronan
      (sHA); cartilage oligomeric matrix protein (sCOMP); keratan sulfate (sKS-5D4);
      transforming growth factor beta (sTGF-ss1); and collagen II-related epitopes
      (sCPII, uCTXII, and uC2C). Activity was monitored by an accelerometer. RESULTS:
      All serum biomarkers increased and one of the urinary biomarkers decreased after
      1 h of non-exertional activity. Food consumption following activity was
      associated with a return of biomarker concentrations to baseline levels.
      Accelerometers proved to be a novel way to monitor protocol compliance and
      demonstrated a positive association between the mean level of activity and sCOMP
      concentration. Urinary CTXII varied the least but demonstrated both true
      circadian variation (peak in the morning and nadir in the evening) and the most
      robust correlation with radiographic knee OA. CONCLUSIONS: We confirm activity
      related variation in these markers. These data suggested that biomarkers also
      varied due to upright posture, glomerular filtration rate stimulated by food
      intake, and circadian rhythm in the case of uCTXII.

PMID- 18727925
TI  - Adenosine A1 and A3 receptors protect astrocytes from hypoxic damage.
AB  - Brain levels of adenosine are elevated during hypoxia. Through effects on
      adenosine receptors (A(1), A(2A), A(2B) and A(3)) on astrocytes, adenosine can
      influence functions such as glutamate uptake, reactive gliosis, swelling, as well
      as release of neurotrophic and neurotoxic factors having an impact on the outcome
      of metabolic stress. We have studied the roles of these receptors in astrocytes
      by evaluating their susceptibility to damage induced by oxygen deprivation or
      exposure to the hypoxia mimic cobalt chloride (CoCl(2)). Hypoxia caused ATP
      breakdown and purine release, whereas CoCl(2) (0.8 mM) mainly reduced ATP by
      causing cell death in human D384 astrocytoma cells. Further experiments were
      conducted in primary astrocytes prepared from specific adenosine receptor knock
      out (KO) and wild type (WT) mice. In WT cells purine release following CoCl(2)
      exposure was mainly due to nucleotide release, whereas hypoxia-induced
      intracellular ATP breakdown followed by nucleoside efflux. N
      ethylcarboxamidoadenosine (NECA), an unselective adenosine receptor agonist,
      protected from cell death following hypoxia. Cytotoxicity was more pronounced in
      A(1)R KO astrocytes and tended to be higher in WT cells in the presence of the
      A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Genetic
      deletion of A(2A) receptor resulted in less prominent effects. A(3)R KO glial
      cells were more affected by hypoxia than WT cells. Accordingly, the A(3) receptor
      agonist 2-chloro-N(6)-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine (CL-IB-MECA)
      reduced ATP depletion caused by hypoxic conditions. It also reduced apoptosis in
      human astroglioma D384 cells after oxygen deprivation. In conclusion, the data
      point to a cytoprotective role of adenosine mediated by both A(1) and A(3)
      receptors in primary mouse astrocytes.

PMID- 18727926
TI  - Pleiotrophin prevents cocaine-induced toxicity in vitro.
AB  - Pleiotrophin is a cytokine involved in differentiation, survival and repair
      processes in the central nervous system. Pleiotrophin is upregulated in the brain
      after administration of different drugs of abuse, thus suggesting a protective
      role of this cytokine on drug-induced toxicity. We have tested this hypothesis in
      vitro using NG108-15 cells, a line widely used for neurotoxicity studies. It was
      found that pleiotrophin (3 and 6 microM) significantly prevents cocaine (5 mM)
      induced cytotoxicity as measured by the neutral red test. Similar results were
      obtained in PC12 cells, which were found to endogenously express both
      pleiotrophin and its main target, receptor protein tyrosine phosphatase (RPTP)
      beta/zeta. Blockade of pleiotrophin signaling using anti-pleiotrophin antibodies
      (2 microg/ml) did not potentiate cocaine-induced toxicity; interestingly,
      incubation of PC12 cells only with anti-pleiotrophin antibodies significantly
      reduced cellular viability, thus suggesting an important role of endogenous
      pleiotrophin signaling in cell survival. The data suggest that pleiotrophin
      overexpression in response to drugs of abuse may be relevant to prevent drug
      induced toxicity.

PMID- 18727927
TI  - PAR-5359, a well-balanced PPARalpha/gamma dual agonist, exhibits equivalent
      antidiabetic and hypolipidemic activities in vitro and in vivo.
AB  - Peroxisome proliferator-activated receptor (PPAR) alpha and gamma are key
      regulators of lipid homeostasis and insulin resistance. In this study, we
      characterize the pharmacological profiles of PAR-5359, a dual agonist of
      PPARalpha and gamma with well-balanced activities. In transient transactivation
      assay, PAR-5359 (3-(4-(2[4-(4chloro-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-ethoxy)
      phenyl)-(2S)-ethoxy-propionic acid) significantly activated human and mouse
      PPARalpha and gamma without activating PPARdelta. In functional assays using
      human mesenchymal stem cells and human hepatoma HepG2 cells, PAR-5359
      significantly induced adipocyte differentiation and human ApoA1 secretion, which
      coincided with its transactivation potencies against the corresponding human
      receptor subtypes. Interestingly, PAR-5359 showed equivalent potencies against
      the mouse receptor subtypes (alpha and gamma; 2.84 microM and 3.02 microM,
      respectively), which suggests the possibility that PAR-5359 could simultaneously
      activates each subtype of receptors subtype in under physiological conditions. In
      an insulin-resistant ob/ob mouse model, PAR-5359 significantly reduced plasma
      insulin levels, improved insulin sensitivity (HOMA-IR), and completely normalized
      plasma glucose levels. In a severe diabetic db/db mouse model, PAR-5359 dose
      dependently reduced the plasma levels of glucose (ED(30) = 0.07 mg/kg).
      Furthermore, it lowered plasma levels of non HDL- (ED(30) = 0.13 mg/kg) and total
      cholesterol (ED(30) = 0.03 mg/kg) in high cholesterol diet-fed rats for 4 days
      treatment. These results suggest that PAR-5359 has the balanced activities for
      PPARalpha and PPARgamma in vivo as well as in vitro. And its balanced activities
      may render PAR-5359 as a pharmacological tool in elucidating the complex roles of
      PPARalpha/gamma dual agonists.

PMID- 18727928
TI  - A new brain area affected by 3,4-methylenedioxymethamphetamine: A microdialysis
      biotelemetry study.
AB  - The widespread abuse of 3,4-methylenedioxymethamphetamine (MDMA) has intensified
      the need to learn more about this drug (e.g. its effects, its mechanism of
      action, brain areas affected). MDMA-induced hyperthermia is a severe
      physiological event not only because it can produce severe adverse consequences
      in human as well as experimental animals, but also because it plays a major role
      in determining the severity of the long-term MDMA-induced neurotoxicity that
      occurs. However, the effects of MDMA on the preoptic anterior hypothalamus, the
      main brain area responsible for control of body temperature, are still unknown.
      In vivo microdialysis-biotelemetry and pharmacological testing were used to
      determine whether the preoptic anterior hypothalamus is among the brain areas
      affected by MDMA by investigating the role of the dopamine neurotransmitter
      system. We examined the effect of a hyperthermic dose of MDMA on the
      extracellular level of dopamine in the preoptic anterior hypothalamus, and
      whether this effect is related to the acute hyperthermic response. The
      administration of a hyperthermic dose of MDMA (20 mg/kg) is accompanied by an
      increase in the extracellular level of dopamine in the preoptic anterior
      hypothalamus. Both the hyperthermia and augmented level of dopamine in the
      preoptic anterior hypothalamus after intraperitoneal injection of MDMA were
      significantly reduced by the pretreatment with D(1)-selective dopamine receptor
      antagonist, R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3
      benzapine (SCH 23390). These data provide the first in vivo evidence that the
      effects of MDMA extend to preoptic anterior hypothalamus.

PMID- 18727929
TI  - Therapy of metronidazole with azathioprine to prevent postoperative recurrence of
      Crohn's disease: a controlled randomized trial.
AB  - BACKGROUND & AIMS: More than 80% of Crohn's disease (CD) patients undergoing
      resection suffer recurrence of their disease. Therapy with aminosalicylates,
      antimetabolites, or antibiotics leads to a modest reduction in the incidence of
      recurrence. GOAL: We sought to examine whether metronidazole for 3 months
      together with azathioprine (AZA) for 12 months is superior to metronidazole alone
      to reduce recurrence of postoperative CD in "high-risk" patients. METHODS: CD
      patients undergoing curative ileocecal resection with >or=1 risk factor for
      recurrence received metronidazole (3 months) and AZA/placebo (12 months). The
      primary end point was the proportion of patients with significant endoscopic
      recurrence 3 and 12 months after surgery. Secondary end points included clinical
      recurrence, safety, and tolerability of treatment. RESULTS: Eighty-one patients
      were randomized; 19 discontinued the study early. Significant endoscopic
      recurrence was observed in 14 of 32 (43.7%) patients in the AZA group and in 20
      of 29 (69.0%) patients in the placebo group at 12 months postsurgery (P = .048).
      Intention-to-treat analysis revealed endoscopic recurrence in 22 of 40 (55%) in
      the AZA group and 32 of 41 (78%) in the placebo group at month 12 (P = .035). At
      month 12, 7 of 32 patients had no endoscopic lesions in the AZA group, versus 1
      of 29 in the placebo group (P = .037). CONCLUSIONS: Despite the enhanced risk of
      recurrence, the overall incidence of significant recurrence was rather low,
      probably owing to the metronidazole treatment that all patients received.
      Concomitant AZA resulted in lower endoscopic recurrence rates and less severe
      recurrences 12 months postsurgery, predicting a more favorable clinical outcome.
      This combined treatment seems to be recommendable to all operated CD patients
      with an enhanced risk for recurrence.

PMID- 18727931
TI  - Intra-arterial transplantation of bone marrow mononuclear cells immediately after
      reperfusion decreases brain injury after focal ischemia in rats.
AB  - AIMS: Transplantation of bone marrow cells has been reported to exert
      neuroprotection against cerebral ischemia. However, the effect of bone marrow
      mononuclear cells (BMMCs) administered immediately after reperfusion has rarely
      been investigated. The present study was designed to examine whether brain injury
      in response to transient focal ischemia can be ameliorated by BMMC administration
      immediately after reperfusion in rats, and to determine whether there are
      differences in the route of administration. MAIN METHODS: Autologous BMMCs were
      obtained from each rat. Rats were then subjected to transient focal ischemia
      followed by BMMC administration via the ipsilateral carotid artery (IA group) or
      the femoral vein (IV group) immediately after reperfusion. Control rats underwent
      the same procedure but received vehicle injection. Infarct volume was compared
      among the groups 24 h and 7 days after reperfusion. BMMCs were fluorescently
      labeled with PKH26 prior to administration to track transplanted cells. KEY
      FINDINGS: Total infarct volume decreased in the IA group, but not in the IV
      group, when compared to the vehicle group. In the ipsilateral hemisphere, PKH26
      positive cell count was greater in the IA group than in the IV group. Motor
      function, assessed with a rotarod test, improved in the IA group compared to the
      vehicle group. SIGNIFICANCE: These results show significant neuroprotection after
      transient focal ischemia by 1 x 10(7) autologous BMMCs administered intra
      arterially, but not intravenously, immediately after reperfusion in rats. The
      larger number of transplanted BMMCs in the brain during the early stage of
      reperfusion may be responsible for the protective effect.

PMID- 18727930
TI  - Prospective study of dietary fiber, whole grain foods, and small intestinal
      cancer.
AB  - BACKGROUND & AIMS: Although a number of epidemiologic studies have found dietary
      fiber and whole grains to be inversely associated with colorectal cancer
      incidence, studies of dietary and other risk factors for small intestinal cancer
      have been sparse and all of a case-control design. We conducted a prospective
      cohort study to determine the relationship between intake of dietary fiber/whole
      grains and the incidence of small intestinal cancer. METHODS: We analyzed dietary
      data collected in 1995 and 1996 from 293,703 men and 198,618 women in the
      National Institutes of Health-AARP Diet and Health Study. We used multivariate
      Cox proportional hazards models to estimate relative risk (RR) and 2-sided 95%
      confidence intervals (CIs) for quintiles of dietary fiber and whole grain intake.
      RESULTS: Through 2003, 165 individuals developed small intestinal cancers.
      Dietary fiber/whole grain intake was generally associated with a lower risk of
      small intestinal cancer. The multivariate RRs (95% CIs; 5th vs 1st intake
      quintile) were 0.79 (0.43-1.44; P trend, .41) for total dietary fiber, 0.51 (0.29
      0.89; P trend, .01) for fiber from grains, and 0.59 (0.33-1.05; P trend, .06) for
      whole grain foods. CONCLUSIONS: Intake of fiber from grains and whole-grain foods
      was inversely associated with small intestinal cancer incidence; the RR values
      were consistent with those from the same dietary factors for large bowel cancer
      in this cohort. In conjunction with the anatomic and physiologic commonalities of
      the large and small bowel, as well as the mutually increased risks for second
      cancer for both organs, grain fiber and whole grain foods seem to protect against
      lower gastrointestinal cancers.

PMID- 18727932
TI  - Vibromyography of oral processing varies with type of semi-solid food and with
      sensory judgements.
AB  - Vibromyography was used to quantify oral activity during the processing of well
      characterized semi-solid model foods whilst subjects assessed the intensity of
      the sensory attributes to thick, creamy, melting, fatty, rough and liking. A
      series of eleven starch-based vanilla custard desserts was prepared with five
      different viscosities, three different fat levels, and three different particle
      sizes. Over 5 sessions, subjects (N=10) took 5 ml spoonfuls of each of the
      stimuli for 5 s before they rated the strength of the various attributes. The
      results demonstrated that oral movements varied significantly with the type of
      semi-solid food and with the type of attribute. Individual subjects displayed a
      highly idiosyncratic behaviour. Oral movements were significantly related to
      sensory ratings of liking, creaminess and roughness.

PMID- 18727933
TI  - Early correlates of visual awareness following orientation and colour rivalry.
AB  - Binocular rivalry occurs when dissimilar images are presented to corresponding
      retinal regions of the two eyes: visibility alternates irregularly between the
      two images, interspersed by brief transitions when parts of both may be visible.
      We measured event-related potentials (ERPs) following binocular rivalry by
      changing the stimulus viewed by one eye to be identical to that in the other eye,
      eliciting binocular fusion. Because of the rivalry, observers either saw the
      change, when it happened to the visible stimulus, or did not see the change, when
      it happened to the invisible stimulus. The earliest ERP differences between
      visible and invisible changes occurred after about 100 ms (P1) when the rivalry
      was between stimuli differing in orientation, and after about 200 ms (N1) when
      the rivalry was between stimuli differing in colour. These differences originated
      from ventro-lateral temporal and prefrontal areas. We conclude that the rivalling
      stimulus property influences the timing of modulation of correlates of visual
      awareness in a property-independent cortical network.

PMID- 18727934
TI  - The antiemetic interaction of Delta9-tetrahydrocannabinol when combined with
      tropisetron or dexamethasone in the least shrew.
AB  - 5-HT3 receptor antagonists (e.g. tropisetron) combined with dexamethasone are
      effective for the acute phase of cisplatin (CIS)-induced emesis. This study
      determined the possible additive or synergistic antiemetic efficacy of Delta9-THC
      when combined with tropisetron or dexamethasone (DEX). Delta9-THC (0-10 mg/kg
      i.p.) was injected in combination with tropisetron (0-5 mg/kg i.p.) or
      dexamethasone (0-20 mg/kg i.p.) prior to CIS (20 mg/kg i.p.) in the least shrew,
      and the induced emesis was recorded for 60 min. CIS-induced vomiting was dose
      dependently and significantly attenuated by individual administration of Delta9
      THC (59-97% reductions) and tropisetron (79-100% attenuation), but not
      dexamethasone (26-40%), although a trend (p<0.1) towards reduced vomiting
      frequency following DEX was noted. Low doses of Delta9-THC (0.25 or 0.5 mg/kg)
      when combined with low doses of tropisetron (0.025, 0.1, or 0.25 mg/kg) were more
      efficacious in reducing emesis frequency than when given individually, but Delta9
      THC had no antiemetic interactions with DEX. However, no tested combination
      provided a significantly greater effect on the number of animals vomiting than
      their individually-administered counterparts. The modest interaction of Delta9
      THC with tropisetron suggests they activate overlapping antiemetic mechanisms,
      while the lack of interaction with dexamethasone needs further clarification.

PMID- 18727935
TI  - Brain temperature responses to salient stimuli persist during dopamine receptor
      blockade despite a blockade of locomotor responses.
AB  - We examined how an acute dopamine (DA) receptor blockade affects locomotor and
      brain (nucleus accumbens or NAcc), muscle and skin temperature responses to three
      arousing stimuli (procedure of sc injection, tail-pinch and social interaction
      with another male rat) and intravenous cocaine (1 mg/kg). DA receptor blockade
      was induced by mixture of D1- (SCH23390) and D-2 selective (eticlopride) DA
      antagonists at 0.2 mg/kg doses. Each arousing stimulus and cocaine caused
      locomotor activation, prolonged increase in NAcc and muscle temperature (0.6-1.0
      degrees C for 20-50 min) and transient skin hypothermia (-0.6 degrees C for 1-3
      min) in drug-naive conditions. DA receptor blockade strongly decreased basal
      locomotor activity, but moderately increased brain, muscle and skin temperatures.
      Therefore, selective interruption of DA transmission does not inhibit the brain,
      making it more metabolically active and warmer despite skin vasodilatation and
      the enhanced heat loss to the body and the external environment. DA antagonists
      strongly decreased locomotor responses to all stimuli and cocaine, had no effects
      on acute skin vasoconstriction, but differentially affected stimuli- and drug
      induced changes in NAcc and muscle temperatures. While brain and muscle
      temperatures induced by cocaine were fully blocked and both temperatures slightly
      decreased, temperature increases induced by tail-pinch and social interaction,
      despite a significant attenuation, persisted during DA receptor blockade. These
      data are discussed to define the role of the DA system in regulating the central
      activation processes and behavioral responsiveness to natural arousing and drug
      stimuli.

PMID- 18727936
TI  - Vitamin D and skeletal muscle tissue and function.
AB  - This review aims to summarize current knowledge on the role of vitamin D in
      skeletal muscle tissue and function. Vitamin D deficiency can cause a myopathy of
      varying severity. Clinical studies have indicated that vitamin D status is
      positively associated with muscle strength and physical performance and inversely
      associated with risk of falling. Vitamin D supplementation has shown to improve
      tests of muscle function, reduce falls, and possibly impact on muscle fiber
      composition and morphology in vitamin D deficient older adults. Molecular
      mechanisms of vitamin D action on muscle tissue include genomic and non-genomic
      effects via a receptor present in muscle cells. Genomic effects are initiated by
      binding of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] to its nuclear receptor, which
      results in changes in gene transcription of mRNA and subsequent protein
      synthesis. Non-genomic effects of vitamin D are rapid and mediated through a cell
      surface receptor. Knockout mouse models of the vitamin D receptor provide insight
      into understanding the direct effects of vitamin D on muscle tissue. Recently,
      VDR polymorphisms have been described to affect muscle function. Parathyroid
      hormone which is strongly linked with vitamin D status also may play a role in
      muscle function; however, distinguishing its role from that of vitamin D has yet
      to be fully clarified. Despite the enormous advances in recent decades, further
      research is needed to fully characterize the exact underlying mechanisms of
      vitamin D action on muscle tissue and to understand how these cellular changes
      translate into clinical improvements in physical performance.

PMID- 18727938
TI  - An alternative Candida spp. cell wall disruption method using a basic sorbitol
      lysis buffer and glass beads.
AB  - This report describes a modified, cost-effective method of cell wall disruption
      for the yeast Candida spp., which employs the use of glass beads in a simple
      sorbitol lysis buffer. This method can be used in conjunction with a commercial
      RNA or genomic DNA isolation method to obtain high-quality RNA or DNA.

PMID- 18727937
TI  - Baculovirus surface display of E(rns) envelope glycoprotein of classical swine
      fever virus.
AB  - Classical swine fever virus (CSFV) causes significant losses in the pig industry
      in many countries. E(rns) is an envelope glycoprotein of CSFV which is known to
      induce virus-neutralizing antibodies and protective immunity in the natural host.
      In this study, one recombinant baculoviruses BacSC-E(rns) expressing histidine
      tagged E(rns) with the transmembrane domain (TM) and cytoplasmic domain (CTD)
      derived from baculovirus envelope protein gp64 was constructed and its immunizing
      efficacy was evaluated in a mouse model. After infection, E(rns) was expressed
      and anchored on the plasma membrane of Sf-9 cells, as demonstrated by Western
      blot and confocal microscopy. Immunogold electron microscopy demonstrated that
      the E(rns) glycoprotein was successfully displayed on the baculoviral envelope.
      Vaccine tests in animals showed that BacSC-E(rns) elicited significantly higher
      E(rns) antibody titers in the immunized mouse models than the control group. This
      demonstrates that the BacSC-E(rns) vaccine can be used potentially against CSFV
      infections. This is the first report demonstrating the potential of E(rns)
      pseudotyped baculovirus as a CSFV vaccine.

PMID- 18727939
TI  - In situ gene expression in cheese matrices: application to a set of enterococcal
      genes.
AB  - Transcriptional approaches are increasingly used to compare the behaviour of
      pathogenic and non-pathogenic bacteria in different culture conditions. The
      purpose of this study was to apply these methods in cheese to better characterize
      food and clinical Enterococcus faecalis isolates during cheese processing.
      Because of the complex biochemical composition of the cheese matrix, e.g. the
      presence of casein and fat, we developed an efficient method to recover total RNA
      from bacteria in a semi-hard cheese model. To validate the RNA extraction method,
      we analysed expression of 7 genes from two E. faecalis strains (one clinical and
      one food isolate) in both cheese and culture medium by semi-quantitative RT-PCR.
      We then used PCR-based DNA macro-arrays to compare expression of 154 genes from
      two E. faecalis strains in both cheese and culture medium. The food strain
      isolated from cheese is transcriptionally active in cheese, as reflected by the
      higher transcript levels of various genes. Conversely, overall transcript levels
      of the V583 clinical isolate were lower in cheese, suggesting that the food
      strain may be more adapted to a dairy environment than the clinical strain. The
      method described here constitutes a very promising tool for future transcriptomic
      studies in cheese matrices. Global profiling in foods may prove to be a valid
      criterion for differentiating food from clinical isolates.

PMID- 18727940
TI  - Event-related potentials and event-related oscillations during identity and
      facial emotional processing in schizophrenia.
AB  - Impairments in emotional recognition have been consistently reported in
      schizophrenic patients. The main aim of the present study was to evaluate time
      sequenced responses in ERPs and event-related oscillations during emotional
      recognition of happiness and fear compared to facial identity recognition in
      schizophrenic patients (SCH) versus healthy controls (CON). Ten paranoid SCH and
      ten CON subjects performed three oddball paradigm tasks, evaluating face identity
      recognition and facial emotional recognition of happiness and fear. Event-related
      potentials and event-related theta and alpha oscillations were obtained for each
      task. N170 and P2 components appeared with higher amplitude in SCH than in CON at
      the occipital locations. An early prefrontally distributed P3a component was
      observed while doing the identity task with lower amplitude in SCH than in CON.
      Comparatively, P3b amplitude was lower in SCH than in CON over parietal leads in
      the identity and happiness tasks. Additionally, theta oscillations showed
      significantly lower RMS values in SCH between 250 and 500 ms post-stimuli in
      frontal and central regions. On the other hand, the grand-averaged alpha
      oscillations demonstrated higher RMS values in the occipital leads in SCH
      compared to CON and the opposite over the frontal regions. Results are
      interpreted in the framework of a functional disruption in the distributed
      neuronal networks involved both in facial identity and emotional recognition in
      schizophrenics as indexed by the brain oscillatory activity and related ERP
      components.

PMID- 18727941
TI  - Negative brain: an integrative review on the neural processes activated by
      unpleasant stimuli.
AB  - Evolutionary pressure has led the nervous system to guarantee rapid and intense
      responses to negative events (dangerous, harmful or repugnant). Thus, the
      'negative brain' (the set of neural mechanisms triggered by unpleasant or
      negative stimuli) is equipped with several specific characteristics. This review
      organizes the current data on the human negative brain in three blocks. Firstly,
      the "Input mechanisms" block describes those structures responsible for the rapid
      distribution of all sensory information. Secondly, the "Evaluation systems" block
      refers to the key pieces: those responsible for evaluating negative consequences
      of stimulation and deciding which response is the most appropriate for coping
      with them. Thirdly, the "Associated and output processes" block describes how
      evaluative elements may interact with other brain structures to modulate
      attention, store and recover situational information, activate defense/withdrawal
      motor programs (or plan new actions) and develop autonomic/motor actions to cope
      with the unpleasant event. Finally, an integrative summary that serves as a
      tentative model of the negative brain is provided.

PMID- 18727942
TI  - Importance of cholesterol for infection of cells by transmissible gastroenteritis
      virus.
AB  - In this study, we addressed the question whether cholesterol is important for
      transmissible gastroenteritis virus (TGEV), a porcine coronavirus, in the
      initiation of an infection. We found that cholesterol depletion from the cellular
      membrane by methyl-beta-cyclodextrin (MbetaCD) significantly impaired the
      efficiency of TGEV infection. Infectivity was also reduced after depleting
      cholesterol from the viral envelope. This finding is surprising because
      coronaviruses bud from a pre-Golgi compartment which is expected to be low in
      cholesterol compared to the plasma membrane. Addition of exogenous cholesterol
      resulted in a restoration of the infectivity confirming our conclusion that
      efficient TGEV infection requires cholesterol in both the viral and the cellular
      membranes. Our data raise the possibility that the viral and cellular proteins
      involved in the entry process may be associated with cholesterol-rich membrane
      microdomains.

PMID- 18727943
TI  - Characterization of carbosilane dendrimers as effective carriers of siRNA to HIV
      infected lymphocytes.
AB  - One of the primary limitations of RNA interference as a technique for gene
      regulation is effective delivery of siRNA into the target cells. Dendrimers are
      nanoparticles that are increasingly being used as oligonucleotide and drug
      delivery vehicles. We have developed amino-terminated carbosilane dendrimers
      (CBS) as a means to protect and transport siRNA. Initially, stability studies
      showed that CBS bind siRNA via electrostatic interactions. Dendrimer-bound siRNA
      was found to be resistant to degradation by RNase. Cytotoxicity assays of
      CBS/siRNA dendriplexes with peripheral blood mononuclear cells (PBMC) and the
      lymphocytic cell line SupT1 revealed a maximum safe dendrimer concentration of 25
      microg/ml. Next, utilizing flow cytometry and confocal microscopy, lymphocytes
      were seen to be successfully transfected by fluorochrome-labeled siRNA either
      naked or complexed with CBS. Dendriplexes with +/- charge ratio of 2 were
      determined to have the highest transfection efficiency while maintaining a low
      level of toxicity in these systems including hard-to-transfect HIV-infected PBMC.
      Finally, CBS/siRNA dendriplexes were shown to silence GAPDH expression and reduce
      HIV replication in SupT1 and PBMC. These results point to the possibility of
      utilizing dendrimers such as CBS to deliver and transfect siRNA into lymphocytes
      thus allowing the use of RNA interference as a potential alternative therapy for
      HIV infection.

PMID- 18727944
TI  - Experimental study on cell self-sealing during sonoporation.
AB  - Reparable sonoporation of human breast cancer cells was achieved during exposure
      to moderate ultrasound (spatial peak acoustic pressure, p(sp)=0.25 MPa, 1 MHz
      tone-bursts, 20 cycles per tone-burst at pulse repetition frequency of 10 kHz) up
      to 40 s assisted by the presence of encapsulated microbubbles (EMBs). It was
      demonstrated that shear stress generated by oscillating EMBs at the cell
      membranes introduced small transient pores in cell membranes by which cells were
      able to uptake some extracellular fluid and meanwhile triggered the repairing
      process through self-sealing during sonoporation. It was also indicated by post
      sonoporation analysis using the fluorescent microscopy, scanning electron
      microscopy, and the Bradford assay which determined the protein content in cell
      supernatant that the self-sealing might be established by lysosomal-associated
      membrane protein, LAMP-1, fusing with the plasma membrane under the stressful
      condition in sonoporation.

PMID- 18727945
TI  - Usefulness of cell-penetrating peptides to improve intestinal insulin absorption.
AB  - Cell-penetrating peptides (CPPs) are a useful tool for delivering therapeutic
      macromolecules across cell membranes. We previously devised an approach using
      CPPs without intermolecular cross-linking and showed the efficient delivery of
      insulin from the intestine to the systemic circulation using a typical CPP,
      oligoarginine. However, this approach required relatively high doses of the CPP.
      Therefore, this study aimed to identify CPPs that are more effective for the
      delivery of insulin and do not induce toxic effects on the intestine. In this
      study, we examined the effects of various types of CPPs including arginine-rich
      peptides and amphipathic peptides that aid insulin absorption from rat ileal
      segments. Among these peptides, coadministration of insulin with R8, penetratin,
      pVEC, and RRL helix significantly increased ileal insulin absorption compared
      with insulin administration alone. In the case of R8, the D-form of the peptide
      had stronger absorption enhancing ability than the L-form. In contrast, the other
      three peptides exerted a more significant effect when the L-forms were applied,
      and L-penetratin had the strongest ability to enhance intestinal insulin
      absorption. Meanwhile, in a physical mixture of CPP and insulin, aggregates
      formed in the solution when high concentrations of CPPs were present. L
      penetratin enhanced insulin absorption even when administered in an aggregated
      solution. We then showed that aggregates of L-penetratin and insulin were broken
      down in the presence of intestinal degradation enzymes. Thus, among CPPs used in
      this study, L-penetratin had the strongest ability to improve insulin intestinal
      absorption.

PMID- 18727946
TI  - Controlled release of vitamin B2 using mesoporous materials functionalized with
      amine-bearing gate-like scaffoldings.
AB  - A study on the controlled release of vitamin B(2) in pure water from mesoporous
      silica-based materials containing a pH- and anion-controlled nano-supramolecular
      gate-like ensembles built up by anchoring suitable polyamines on the external
      surface is reported (solid S1). This solid contains the vitamin (the delivered
      molecule) onto the pores, whereas the amine-based gate-like ensemble is anchored
      on the pore outlets. To obtain solid S1 the mesoporous MCM-41 support was first
      synthesized using tetraethyl orthosilicate (TEOS) as hydrolytic inorganic
      precursor and the surfactant hexadecyltrimethylammonium bromide (CTAB) as porogen
      species. Calcination of the mesostructured phase resulted in the starting solid.
      Then, first the vitamin and the latter an excess of 3-[2-(2
      aminoethylamino)ethylamino]propyl-trimethoxysilane were added to the suspension
      containing the MCM-41 scaffolding and stirred. Solid S1 was characterized using
      standard solid state procedures. It was found that the functionalization process
      and the inclusion of the vitamin on the pores do not modify the mesoporous
      structure of the starting material. Delivery studies in water were carried out at
      pH 2 and 7. At pH 2 all the anions studied (sulfate, phosphate, GMP and ATP)
      strongly hinder vitamin release (C(anion)=1 x 10(-2) mol dm(-3)), whereas at pH 7
      the delivery was observed for sulfate and GMP whereas the gate remained closed in
      the presence of ATP and phosphate. Selective delivery at neutral pH and no
      liberation in acidic conditions can also be controlled with ATP and GMP using a
      suitable concentration of anion. The remarkable anion-controllable response of
      the gate-like ensemble at a certain pH can be explained in terms of anion complex
      formation with the tethered polyamines. Finally, selectivity patterns have been
      discussed in terms of kinetic rates of vitamin B(2) release. The pH-controlled
      gate-like scaffoldings on S1 might be a suitable prototype for the development of
      orally applicable delivery systems designed to have the particular ability to
      protect the cargo from the acidic conditions of the stomach (acid pH, gate
      closed) but will release the load at the intestine (basic pH, gate open).

PMID- 18727947
TI  - Rare neuropsychiatric sequelae following neuroleptic malignant syndrome: a case
      report and review of the literature.

PMID- 18727948
TI  - A 12-week, double-blind, placebo-controlled trial of donepezil adjunctive
      treatment to risperidone in chronic and stable schizophrenia.
AB  - There is considerable incentive to develop new treatment strategies that
      effectively target cognitive deficits in schizophrenia. One of the theoretically
      promising novel treatment candidates is acetylcholinesterase inhibitors that
      increase the synaptic levels of cholinergic, nicotinic, and muscarinic receptor
      activity. The purpose of this study was to assess the efficacy of donepezil as an
      adjuvant agent in the treatment of chronic schizophrenia in particular for
      cognitive impairments. This investigation was a 12-week, double-blind study of
      parallel groups of patients with stable chronic schizophrenia. Thirty patients
      were recruited from inpatient and outpatient departments, age ranging from 22 to
      44 years. All participants met DSM-IV-TR. diagnostic criteria for schizophrenia.
      To be eligible, patients were required to have been treated with a stable dose of
      risperidone as their primary antipsychotic treatment for a minimum period of 8
      weeks. The subjects were randomized to receive donepezil (10 mg/day) or placebo,
      in addition to risperidone (4-6 mg/day). Clinical psychopathology was assessed
      with Positive and Negative Syndrome Scale (PANSS). Cognition was measured by a
      cognitive battery. Patients were assessed by a psychiatrist at baseline and after
      8, and 12 weeks after the medication started. The PANSS scores and cognitive
      performance were used as the outcome measures. The donepezil group had
      significantly greater improvement in the negative symptoms over the 12-week
      trial. There were no differences between the donepezil and placebo groups on any
      neurocognitive assessments at endpoint (week 12). The present study indicates
      donepezil as a potential adjunctive treatment strategy for negative symptoms of
      chronic schizophrenia.

PMID- 18727949
TI  - Sex differences in memory processing in schizophrenia: an event-related potential
      (ERP) study.
AB  - Recently, research has begun to examine sex differences in cognitive functions in
      schizophrenia and whether such sex differences reflect normal, exaggerated, or
      reversed sexual dimorphism. This study examined this question by using event
      related potentials (ERPs). ERPs were recorded in a recognition memory task in 18
      patients and 18 matched control subjects. On an early frontal component, the
      results show an interaction between sex and pathological condition that results
      in an apparent reversed sexual dimorphism. On mid-latency components, patients
      show no sex difference on a frontal component, but a difference on the posterior
      component, whereas healthy subjects show a reverse pattern. Finally, late
      components show sex difference in the same direction as healthy subjects. These
      results indicate that the influence of sex on the cognitive impairment in
      schizophrenia is not homogenous across the information-processing cascade.

PMID- 18727950
TI  - Comparison of the behavioural pharmacology of the Lister-Hooded with 2 commonly
      utilised albino rat strains.
AB  - The use of animal models (particularly rats) in research for developing drugs for
      central nervous system diseases is well validated. However a range of strains are
      often utilised in these models. The Lister-Hooded (LH) strain is beginning to be
      increasingly used in preclinical investigations. Thus, the objective of the
      present study was to investigate the comparative behavioural pharmacology of this
      strain, with the two most widely used rat strains, namely the Sprague-Dawley
      (SD), and Wistar (W) strains. The tests used were the forced swim test (FST) for
      antidepressants, the amphetamine-locomotor activity test for antipsychotics, the
      elevated plus maze (EPM) for anxiolytics, as well as tests of general locomotor
      activity using home cage monitoring (HCM) and the open field test. Continuous HCM
      revealed a significantly higher daily activity and lower nocturnal activity for
      LH compared to the other strains; there were no strain-related differences in the
      open field test. In the FST, there were no strain differences in immobility time
      and a similar magnitude of desipramine-induced reduction in immobility across
      strains. In the locomotor activity test, control LH rats showed significantly
      higher activity whilst significant amphetamine-induced hyperactivity was seen
      only with the LH and W strains. In the EPM, control LH rats had a significantly
      larger percentage of open arm entries, whilst only the SD strain displayed a
      significant diazepam-induced increase in this parameter. These findings suggest
      that strain variation can cause markedly different results in behavioural
      pharmacological tests where locomotor activity plays a significant role, and
      should be taken into account when selecting a strain for evaluating the
      behavioural effects of psychotropic drugs. Such differences in locomotor activity
      in the LH strain could be accounted for by an altered diurnal pattern in this
      strain.

PMID- 18727951
TI  - Analytical criteria for performance characteristics of IgE binding methods for
      evaluating safety of biotech food products.
AB  - There is detailed guidance on how to perform bioinformatic analyses and enzymatic
      degradation studies for genetically modified crops under consideration for
      approval by regulatory agencies; however, there is no consensus in the scientific
      community on the details of how to perform IgE serum studies. IgE serum studies
      are an important safety component to acceptance of genetically modified crops
      when the introduced protein is novel, the introduced protein is similar to known
      allergens, or the crop is allergenic. In this manuscript, we describe the
      characteristics of the reagents, validation of assay performance, and data
      analysis necessary to optimize the information obtained from serum testing of
      novel proteins and genetically modified (GM) crops and to make results more
      accurate and comparable between different investigations.

PMID- 18727952
TI  - Selective resistance of taurine-fed mice to isoniazide-potentiated seizures: in
      vivo functional test for the activity of glutamic acid decarboxylase.
AB  - Taurine, 2-aminoethanesulfonic acid, is one of the most abundant free amino acids
      especially in excitable tissues, with wide physiological actions. We have
      previously reported that in mice, supplementation of the drinking water with
      taurine induces alterations in the inhibitory GABAergic system. In taurine-fed
      mice we found that the expression level of glutamic acid decarboxylase (GAD), the
      enzyme responsible for GABA synthesis, is elevated. Increased expression of GAD
      was accompanied by increased levels of GABA. Here, we investigated
      pharmacologically the functional significance of taurine-induced increase in GAD
      expression by determining the threshold for kainic acid-induced seizures after
      partial inhibition of GAD activity with isoniazide. We found that taurine-fed
      mice have elevated GAD expression and showed a higher threshold for seizure onset
      when compared with age-matched controls. Thus, taurine-fed mice have a functional
      increase in GAD activity which offers some protection in this seizure model.
      Furthermore, this pharmacological manipulation can be used to determine the level
      of GAD activity in other model systems that show alterations in GAD expression.

PMID- 18727953
TI  - Altered expression and localization of hippocampal A-type potassium channel
      subunits in the pilocarpine-induced model of temporal lobe epilepsy.
AB  - Altered ion channel expression and/or function may contribute to the development
      of certain human epilepsies. In rats, systemic administration of pilocarpine
      induces a model of human temporal lobe epilepsy, wherein a brief period of status
      epilepticus (SE) triggers development of spontaneous recurrent seizures that
      appear after a latency of 2-3 weeks. Here we investigate changes in expression of
      A-type voltage-gated potassium (Kv) channels, which control neuronal excitability
      and regulate action potential propagation and neurotransmitter release, in the
      pilocarpine model of epilepsy. Using immunohistochemistry, we examined the
      expression of component subunits of somatodendritic (Kv4.2, Kv4.3, KChIPl and
      KChIP2) and axonal (Kv1.4) A-type Kv channels in hippocampi of pilocarpine
      treated rats that entered SE. We found that Kv4.2, Kv4.3 and KChIP2 staining in
      the molecular layer of the dentate gyrus changes from being uniformly distributed
      across the molecular layer to concentrated in just the outer two-thirds. We also
      observed a loss of KChIP1 immunoreactive interneurons, and a reduction of Kv4.2
      and KChIP2 staining in stratum radiatum of CA1. These changes begin to appear 1
      week after pilocarpine treatment and persist or are enhanced at 4 and 12 weeks.
      As such, these changes in Kv channel distribution parallel the acquisition of
      recurrent spontaneous seizures as observed in this model. We also found temporal
      changes in Kv1.4 immunoreactivity matching those in Timm's stain, being expanded
      in stratum lucidum of CA3 and in the inner third of the dentate molecular layer.
      Among pilocarpine-treated rats, changes were only observed in those that entered
      SE. These changes in A-type Kv channel expression may contribute to
      hyperexcitability of dendrites in the associated hippocampal circuits as observed
      in previous studies of the effects of pilocarpine-induced SE.

PMID- 18727954
TI  - Strial microvascular pathology and age-associated endocochlear potential decline
      in NOD congenic mice.
AB  - NOD/ShiLtJ (previously NOD/LtJ) inbred mice show polygenic autoimmune disease and
      are commonly used to model autoimmune-related type I diabetes, as well as
      Sjogren's syndrome. They also show rapidly progressing hearing loss, partly due
      to the combined effects of Cdh23ahl and Ahl2. Congenic NOD.NON-H2nb1/LtJ mice,
      which carry corrective alleles within the H2 histocompatibility gene complex, are
      free from diabetes and other overt signs of autoimmune disease, but still exhibit
      rapidly progressive hearing loss. Here we show that cochlear pathology in these
      congenics broadly includes hair cell and neuronal loss, plus endocochlear
      potential (EP) decline from initially normal values after two months of age. The
      EP reduction follows often dramatic degeneration of capillaries in stria
      vascularis, with resulting strial degeneration. The cochlear modiolus also
      features perivascular inclusions that resemble those in some mouse autoimmune
      models. We posit that cochlear hair cell/neural and strial pathology arise
      independently. While sensory cell loss may be closely tied to Cdh23ahl and Ahl2,
      the strial microvascular pathology and modiolar anomalies we observe may arise
      from alleles on the NOD background related to immune function. Age-associated EP
      decline in NOD.NON-H2nb1 mice may model forms of strial age-related hearing loss
      caused principally by microvascular disease. The remarkable strial capillary loss
      in these mice may also be useful for studying the relation between strial
      vascular insufficiency and strial function.

PMID- 18727955
TI  - Analgesic and anti-inflammatory effects of Ligularia fischeri leaves in
      experimental animals.
AB  - AIM OF THE STUDY: The ethanol extract (LF) of Ligularia fischeri var. spiciformis
      (leaf) has been evaluated for antinociceptive and anti-inflammatory activities in
      mice. MATERIALS AND METHODS: Analgesic and anti-inflammatory activities were
      studied by measuring nociception induced by formalin, acetic acid and hot-plate,
      and inflammation induced by carrageenan, formalin, and arachidonic acid. RESULTS:
      The acute treatment of mice with LF at doses of 100 and 200mg/kg, by oral
      administration, produced a significant antinociceptive effect in the acetic acid
      induced writhing, formalin-induced pain licking and hot-plate-induced pain. Also,
      the LF significantly inhibited both carrageenan- and formalin-induced
      inflammation as well as arachidonic acid-induced ear edema in mice. CONCLUSIONS:
      These inhibitions were statistically significant (P<0.05). Thus, our
      investigation suggests a potential benefit of Ligularia fischeri in treating
      conditions associated with inflammatory pain.

PMID- 18727956
TI  - Molecular dating of the diversification of Phyllostominae bats based on nuclear
      and mitochondrial DNA sequences.
AB  - Times of divergence among the three tribes included within the subfamily
      Phyllostominae were estimated using a Bayesian approach to infer dates of
      divergence based on mitochondrial and nuclear sequence data. The subfamily
      Phyllostominae is particularly attractive for such analysis, as it is one of the
      few groups of bats to have fossil specimens. Our molecular time analyses suggest
      that diversification among tribes and genera of phyllostomine bats occurred
      during the Early to Mid-Miocene, and was coincident with diversification events
      in two co distributed taxa: Caviomorph rodents and New World monkeys.

PMID- 18727957
TI  - Thermoregulatory and metabolic responses of Japanese quail to hypoxia.
AB  - Common responses to hypoxia include decreased body temperature (Tb) and decreased
      energy metabolism. In this study, the effects of hypoxia and hypercapnia on Tb
      and metabolic oxygen consumption (VO2) were investigated in Japanese quail
      (Coturnix japonica). When exposed to hypoxia (15, 13, 11 and 9% O2), Tb decreased
      only at 11% and 9% O2 compared to normoxia; quail were better able to maintain Tb
      during acute hypoxia after a one-week acclimation to 10% O2. VO2 also decreased
      during hypoxia, but at 9% O2 this was partially offset by increased anaerobic
      metabolism. Tb and VO2 responses to 9% O2 were exaggerated at lower ambient
      temperature (Ta), reflecting a decreased lower critical temperature during
      hypoxia. Conversely, hypoxia had little effect on T(b) or VO2 at higher Ta (36
      degrees C). We conclude that Japanese quail respond to hypoxia in much the same
      way as mammals, by reducing both Tb and VO2. No relationship was found between
      the magnitudes of decreases in Tb and VO2 during 9% O2, however. Since metabolism
      is the source of heat generation, this suggests that Japanese quail increase
      thermolysis to reduce Tb. During hypercapnia (3, 6 and 9% CO2), Tb was reduced
      only at 9% CO2 while VO2 was unchanged.

PMID- 18727958
TI  - Diclofenac toxicity in Gyps vulture is associated with decreased uric acid
      excretion and not renal portal vasoconstriction.
AB  - Diclofenac (DF), a non-steroidal anti-inflammatory drug (NSAID), is largely
      regarded as one of the most devastating environmental toxicant in recent times,
      after accidental exposure via their food-chain lead to massive mortalities in
      three vulture species on the Asian subcontinent. Although the use of diclofenac
      was recently banned on the Indian subcontinent, following the favourable safety
      profile of meloxicam, its mechanism of toxicity remains unknown. In an attempt to
      establish this mechanism, we test three hypotheses using models established from
      either the domestic chicken (Gallus domesticus) or the African White-backed
      vulture (Gyps africanus). We demonstrate that both DF and meloxicam are toxic to
      renal tubular epithelial (RTE) cells following 12 h of exposure, due to an
      increase in production of reactive oxygen species (ROS), which could be
      temporarily ameliorated by pre-incubation with uric acid (UA). When cultures were
      incubated with either drug for only 2 h, meloxicam showed no toxicity in contrast
      to diclofenac. In both cases no increase in ROS production was evident. In
      addition, diclofenac decreased the transport of uric acid, by interfering with
      the p-amino-hippuric acid (PAH) channel. We conclude that vulture susceptibility
      to diclofenac results from a combination of an increased ROS, interference with
      UA transport and the duration of exposure.

PMID- 18727959
TI  - Reversible regulation of metastasis by ROS-generating mtDNA mutations.
AB  - It has been controversial whether mtDNA mutations are responsible for oncogenic
      transformation (normal cells to develop tumors), and for malignant progression
      (tumor cells to develop metastases). To clarify this issue, we created trans
      mitochondrial cybrids with mtDNA exchanged between mouse tumor cells that express
      different metastatic phenotypes. The G13997A mutation in the ND6 gene of mtDNA
      from high metastatic tumor cells reversibly controlled development of metastases
      by overproduction of reactive oxygen species (ROS), but did not control
      development of tumors. The mtDNA-mediated reversible control of metastasis
      reveals a novel function of mtDNA, and suggests that ROS scavengers may be
      therapeutically effective in suppressing metastasis.

PMID- 18727960
TI  - Regarding "Impact of diabetes mellitus on outcomes of superficial femoral artery
      endoluminal interventions".

PMID- 18727962
TI  - Endovascular management of atherosclerotic renovascular disease: early results
      following primary intervention.
AB  - OBJECTIVE: This retrospective review examines periprocedural morbidity and early
      functional responses to primary renal artery angioplasty and stenting (RA-PTAS)
      for patients with atherosclerotic renovascular disease (RVD). METHODS:
      Consecutive patients undergoing primary RA-PTAS for hemodynamically significant
      atherosclerotic RVD with hypertension and/or ischemic nephropathy were identified
      from a prospectively maintained registry. Hypertension responses were determined
      based on pre- and post-intervention blood pressure measurements and medication
      requirements. Estimated glomerular filtration rate (eGFR) was used to determine
      renal function responses. Both hypertension and renal function responses were
      assessed at least three weeks after RA-PTAS. Stepwise multivariable regression
      analysis was used to examine associations between blood pressure and renal
      function responses to RA-PTAS and select clinical variables. RESULTS: One-hundred
      ten primary RA-PTAS were performed on 99 patients with atherosclerotic RVD with a
      mean angiographic diameter-reducing stenosis of 79.2 +/- 12.9%. All patients had
      hypertension (mean of 3.4 +/- 1.3 antihypertensive agents). Mean pre-intervention
      eGFR was 49.9 +/- 22.7 mL/min/1.73 m(2), and 74 patients had a pre-intervention
      eGFR < 60 mL/min/1.73 m(2). The technical success rate for RA-PTAS was 94.5%. The
      periprocedural complication rate was 5.5%; there were no periprocedural deaths.
      Statistically significant decreases in mean systolic blood pressure (161.3 +/-
      25.2 vs. 148.5 +/- 25.2 post-intervention, P < .0001), diastolic blood pressure
      (78.6 +/- 13.3 versus 72.5 +/- 13.5 post-intervention, P < .0001), and number of
      antihypertensive agents (3.3 +/- 1.2 versus 3.1+/- 1.3 post-intervention, P =
      .009) were observed. Assessed categorically, hypertension response to RA-PTAS was
      cured in 1.1%, improved in 20.5%, and unchanged in 78.4%. Categorical eGFR
      response to RA-PTAS was improved in 27.7%, unchanged in 65.1%, and worsened in
      7.2%. Multivariable stepwise regression revealed associations between pre- and
      post-intervention systolic blood pressure (P < .0001), diastolic blood pressure
      (P < .0001), and eGFR (P < .0001), as well as a trend toward improved diastolic
      blood pressure response among patients managed with staged bilateral intervention
      (P = .0589). CONCLUSION: Primary RA-PTAS for atherosclerotic RVD was associated
      with low peri-procedural morbidity and mortality but only modest early
      improvements in blood pressure and renal function. Results from ongoing
      prospective trials are needed to assess the long term outcomes associated with RA
      PTAS and clarify its role in the management of atherosclerotic RVD.

PMID- 18727964
TI  - Impact of runoff on superficial femoral artery endoluminal interventions for rest
      pain and tissue loss.
AB  - BACKGROUND: While aggressive endoluminal therapy for superficial femoral artery
      (SFA) occlusive disease is commonplace, the implications of runoff on long-term
      outcomes of these interventions in patients with rest pain and tissue loss is
      unclear. Runoff is known to negatively effect graft patency. The aim of this
      study is to examine the impact of distal runoff on long-term outcomes of SFA
      interventions for critical ischemia. METHODS: A prospective database of patients
      undergoing endovascular treatment of the SFA between 1986 and 2007 was queried.
      Patients with Rutherford symptom classification 4, 5, and 6 were selected.
      Patients with concomitant tibial interventions were excluded. Pre-operative
      angiograms were reviewed in all cases to assess distal popliteal and tibial
      runoff and were scored according to modified Society of Vascular Surgery criteria
      for both vessels such that a higher score implies worse runoff (minimum 1 and
      maximum 19). Three runoff score groups were identified: <5 (good), 5-10
      (compromised), and >10 (poor). Kaplan-Meier survival analyses were performed to
      assess time-dependent outcomes. Multivariate and factor analyses were performed.
      RESULTS: Three hundred six limbs in 241 patients (57% male, mean age 68 years)
      underwent endovascular treatment for critical ischemia (44% rest pain and 56%
      tissue loss.) Technical success was 96% with 61% SFA undergoing angioplasty, 37%
      SFA primary stenting and 2% SFA an atherectomy. Overall mortality was 1% and
      overall morbidity was 16% at 90 days after the procedure. At 5 years, vessels
      with compromised and poor runoff had significantly worse cumulative patency (82
      +/- 9%, 56 +/- 4%, and 52 +/- 7% for good, compromised, and poor runoffs,
      respectively, mean +/- standard error of the mean [SEM]). Freedom from recurrent
      symptoms (65 +/- 8%, 39 +/- 9%, and 18 +/- 9% for good, compromised, and poor
      runoffs, respectively) and limb salvage (65 +/- 5%, 41 +/- 4%, and 20 +/- 6% for
      Good, Compromised, and Poor runoffs, respectively) were incrementally curtailed
      by worsening runoff with significant decreases as runoff category deteriorated.
      CONCLUSIONS: In patients presenting with rest pain and tissue loss who are
      treated with SFA percutaneous interventions, patency is negatively affected by
      compromised and poor runoffs in keeping with the bypass literature. More
      importantly, freedom from recurrent symptoms and limb salvage are incrementally
      curtailed as runoff scores worsen. These findings are consistent with the bypass
      literature.

PMID- 18727968
TI  - First report of a late type III endoleak from fabric tears of a Zenith stent
      graft.
AB  - We report a case of a late type III endoleak from a hole in the fabric of the
      main body of a Zenith bifurcated endograft 7 years after implantation. Abdominal
      pain and a rapidly expanding aneurysm were eventually followed by rupture. The
      defect was detected at open surgery, whereas no evidence of endoleak was found at
      preoperative computed tomography (CT) or angiogram. The defect was repaired by a
      relining procedure with an Excluder stent graft. The patient, however, died 3
      weeks after admission.

PMID- 18727966
TI  - Outcomes of endovascular interventions for TASC II B and C femoropopliteal
      lesions.
AB  - OBJECTIVE: To evaluate outcomes of endovascular interventions on femoropopliteal
      occlusive disease and determine predictors of restenosis of Trans Atlantic Inter
      Societal Consensus (TASC) II B and C lesions. METHODS: All patients undergoing
      endovascular interventions for femoropopliteal occlusive disease between May 2003
      and July 2007 were reviewed. Patient demographics, pre- and post-procedure ankle
      brachial indices (ABI), and anatomic factors (including categorization by TASC II
      classification, lesion length, and runoff vessel status) were analyzed. Outcomes
      evaluated included freedom from restenoses, freedom from re-intervention, overall
      patency, and assisted-patency. RESULTS: A total of 237 total limbs were treated
      during the period reviewed. The study group included 108 TASC B and 32 TASC C
      limbs in 125 patients (mean age 73.1 +/- 10.4 years, male sex: 59%). Seventy-one
      percent of patients were Rutherford classification 2/3 while the remaining 29%
      were Rutherford classification 4/5. Mean follow-up period was 12.7 months (range,
      1-52 m). Forty-one (41) limbs experienced restenosis or occlusion at a mean time
      of 8 months (range, 1-24 m). Freedom from restenosis/occlusion was 58.9% at 12
      months and 47.9% at 24 months. Predictors of restenosis included a preoperative
      ABI <0.5 (hazard ratio [HR] 3.05, 95% confidence interval [CI] 1.36-6.86, P =
      .007) and hypercholesterolemia (HR 2.42, 95% CI 1.11-5.25, P = .025). Lesion
      length as a continuous variable (per centimeter) also correlated with a higher
      risk of restenosis (HR 1.06, 95% CI 1.00-1.12, P = .057). The overall assisted
      primary and secondary-patency rates were 87% and 94% respectively at 3 years with
      no significant differences between TASC B and TASC C limbs. CONCLUSION:
      Endovascular interventions for TASC II B and C lesions are associated with
      restenosis/occlusion rates that are at least as good as those of open
      femoropopliteal bypass surgery from historical, previously published series.
      Furthermore, overall assisted-patency rates are excellent, although low
      preoperative ABIs continue to be associated with worse outcomes.

PMID- 18727969
TI  - Chronic type B dissecting aortoiliac aneurysm repair complicated by congenital
      pelvic kidney.
AB  - Although the association between abdominal aortic aneurysm and pelvic kidney is
      rare, previous reports have described various methods of repair with successful
      preservation of pelvic kidney function. We describe a unique case complicated by
      aortic dissection. Successful intra-operative perfusion of the kidney was
      maintained via a temporary axillorenal shunt.

PMID- 18727970
TI  - Percutaneous treatment of a large superior mesenteric artery pseudoaneurysm and
      arteriovenous fistula: a case report.
AB  - The combination of superior mesenteric artery (SMA) pseudoaneurysm and
      arteriovenous (AV) fistula is a rare complication following penetrating abdominal
      trauma. We report a case of a post-traumatic SMA pseudoaneurysm and large fistula
      between the SMA and superior mesenteric vein (SMV), which was successfully
      treated with an endovascular stent graft.

PMID- 18727971
TI  - Massive upper gastrointestinal bleeding due to a ruptured superior mesenteric
      artery aneurysm duodenum fistula.
AB  - This case report describes sudden massive upper gastrointestinal bleeding due to
      a ruptured superior mesenteric artery aneurysm-duodenal fistula following mitral
      and aortic valvular replacement surgery due to infectious endocarditis. The
      superior mesenteric artery false aneurysm was diagnosed by computed tomography
      scanning. The intraoperative findings included a rupture at the trunk of superior
      mesenteric artery (SMA) and a perforation on the anterior wall of the third
      portion of the duodenum. The patient was treated by emergency surgery, which
      consisted of an interposition repair of the SMA with a saphenous vein graft for
      the superior mesenteric artery and a duodenojejunal Roux-en-Y anastomosis for the
      perforation of the duodenum. At 30-months follow-up, the patient is alive and
      well with no abdominal pain and eating a regular diet.

PMID- 18727972
TI  - Saphenous vein graft aneurysm with graft-enteric fistula after renal artery
      bypass.
AB  - A 65-year-old female presented with upper gastrointestinal hemorrhage thirty
      years following an aorta-to-right renal artery bypass constructed with saphenous
      vein. Upper endoscopy demonstrated a duodenal ulcer, and a CAT scan demonstrated
      aneurysmal degeneration of her renal artery bypass with duodenal impingement.
      Laparotomy demonstrated erosion of the aneurysm through the posterior wall of the
      duodenum; extra-anatomic renovascular reconstruction and primary duodenal repair
      was performed. Although aneurysmal degeneration of intraabdominal saphenous vein
      grafts is well described and rupture likewise reported, this report represents
      the first description of an intraabdominal autogenous vein graft aneurysm
      presenting with gastrointestinal erosion and fistula.

PMID- 18727973
TI  - Combined thenar and hypothenar hammer syndromes: case report and review of the
      literature.
AB  - Patients who use the palms of their hands as a hammer may cause irreversible
      damage to the radial or ulnar arteries. Damage to the intima may lead to arterial
      thrombosis, whereas damage to the media may cause aneurysm formation with
      embolization to the digital arteries, causing symptoms of ischemia. These
      patients may have symptoms of Raynaud syndrome, or they may have ischemic
      ulcerations of their fingers. Hypothenar hammer syndrome with involvement of the
      ulnar artery is much more frequently encountered than thenar hammer syndrome,
      which is caused by damage to the radial artery. We report a patient with
      symptomatic occlusion of both the radial and ulnar arteries secondary to
      repetitive trauma to the palm of his hand. In our review of the literature, we
      found two reports involving a total of four patients with similar findings. Both
      conservative and surgical treatments have been used successfully. Avoidance of
      the precipitating activities is important in long-term management of these
      patients.

PMID- 18727975
TI  - Hyperemic maximal venous outflow unmasks symptomatic lower extremity venous
      obstruction.
AB  - Venous obstruction is an underappreciated and often unrecognized component of the
      pathophysiology of symptomatic chronic venous disease (CVD). Moreover, standard
      methods used to detect venous obstruction, such as maximal venous outflow, are
      inadequate as they typically test patients at rest and in the supine position
      when the pathophysiology of CVD is defined in the upright patient performing
      exercise. This report describes a patient with incapacitating venous claudication
      in whom standard noninvasive venous function tests were normal and whose
      phlebography was interpreted as showing no evidence of venous obstruction. A
      postocclusive reactive hyperemic technique was used to unmask significant outflow
      obstruction, leading to operative correction and subsequent symptom resolution.

PMID- 18727974
TI  - Early Palma procedure after iliac vein injury in abdominal penetrating trauma.
AB  - Ligation for penetrating abdominal vein trauma may have better outcome than a
      vascular reconstruction in an unstable patient. However, symptoms of chronic
      venous insufficiency may appear over time. We describe our surgical experience
      with 4 patients who underwent iliac vein ligation followed by venous bypass with
      a modified Palma derivation between 48 and 240 hours after sustaining penetrating
      abdominal trauma with concomitant iliac vein injury. Patients were assessed for
      venous symptoms and conduit patency with continuous wave Doppler and duplex
      scanning. One graft occluded acutely and the remaining three remain patent with
      functioning valves. In order to preserve venous outflow after severe iliac vein
      injury, we think that venous ligation as a part of damage control surgery
      followed by a modified Palma operation may prevent chronic symptoms of venous
      outflow obstruction without compromising an already injured patient.

PMID- 18727976
TI  - Ergotism.

PMID- 18727977
TI  - A technique for increased accuracy in the placement of the "giant" Palmaz stent
      for treatment of type IA endoleak after endovascular abdominal aneurysm repair.
AB  - We report a deployment technique that eliminates "watermelon seeding" of the
      "giant" Palmaz stent in the treatment of type IA endoleak after endovascular
      abdominal aneurysm repair. A 5010 Palmaz stent (Cordis Corp, Miami Lakes, Fla) is
      asymmetrically hand-crimped on an appropriately sized valvuloplasty balloon that
      assures that the proximal (cranial) aspect will deploy first. A long 16 to 20F
      sheath is placed distal to the target area. Once the balloon and stent assembly
      is in position, the sheath is partially retracted to allow only the proximal
      (cranial) half of the balloon to expand, flaring the unsheathed proximal stent.
      The expanded proximal balloon prevents cranial stent migration. The sheath
      prevents distal (caudal) stent migration. Full retraction of the sheath allows
      the distal balloon and stent to expand, completing the stent deployment.

PMID- 18727978
TI  - Heavily calcified chronic total occlusion of common iliac artery successfully
      treated with Tornus microcatheter and rotational atherectomy.
AB  - A 58-year-old man who required long-term hemodialysis was referred to our
      institution for the management of life-limiting intermittent claudication of the
      right lower extremity. The diagnostic arteriography demonstrated heavily
      calcified chronic total occlusion in the right common iliac artery. The lesion
      was successfully treated with the combination of a Tornus microcatheter (Asahi
      Intecc, Aichi, Japan) and rotational atherectomy. We describe in this article a
      niche application of the Tornus microcatheter and the effect of the combination
      technique of it with rotational atherectomy in peripheral interventions.

PMID- 18727980
TI  - Regarding "Multidisciplinary approach in the management of a giant arteriovenous
      malformation in the right axillary region".

PMID- 18727981
TI  - Regarding "A randomized trial of carotid stenting with and without cerebral
      protection".

PMID- 18727983
TI  - Regarding "Pharmacologic risk factor management in peripheral arterial disease: a
      vade mecum for vascular surgeons".

PMID- 18727985
TI  - The Food and Drug Administration: an agency under siege.

PMID- 18727986
TI  - The weaker sex: is being male a legally cognizable defect, impairment, or
      disability?
AB  - Compared with women, men die from cancer and coronary artery disease in
      disproportionately higher numbers and are more susceptible to a host of emotional
      and developmental disorders. The authors of this article consider what scientific
      proof or evidence would be required to legally recognize "being male" as a
      disability, based on the overwhelming number of physical deficiencies to which
      males are genetically predisposed. The article summarizes major scientific
      findings on male health problems and explores various laws and policies that
      might be implicated by treatment of males as a special category recognized by the
      law. How the law creates categories of individuals and the reasons why these
      categories are created for legal classification are reviewed. In addition, the
      potential for a "maleness" defense in the context of criminal law and procedure
      is assessed. Lastly, the authors examine the policy implications of treating men
      as a disabled class, and consider how judges, juries, and legislators would view
      a scientifically based approach to the creation of a class. Given the many false
      starts in the past, in which the law had embraced what later was shown to be bad
      science, substantial historical baggage will have to be overcome to convince
      judges, juries, and legislators that science has now got it in the sense of
      having established a valid, causal, genetic or biological determinant for
      behavior. The consideration of a "male deficiency" theory under the law would
      have to rely on a more inclusive view of legal "disability" and a willingness to
      allow technologic advances in genetics to inform our understanding of criminal
      behavior.

PMID- 18727987
TI  - Sex-specific differences in the expression levels of estrogen receptor subtypes
      in colorectal cancer.
AB  - BACKGROUND: Altered expression of estrogen receptors alpha and beta (ERalpha and
      ERbeta) has been hypothesized to play a role in carcinogenesis. However, little
      is known about the sex-specific differences of ER expression in colorectal cancer
      (CRC). OBJECTIVE: This study examined ERalpha and ERbeta protein levels in male
      and female patients with CRC. METHODS: Using Western blot analysis, the intensity
      of ERalpha and ERbeta protein levels was determined in tumor tissue and in
      corresponding normal colon mucosa from patients with CRC. RESULTS: All 64 white
      patients (33 men, mean [SEM] age 64.1 [13.1] years, age range 26-90 years; 31
      women, mean age 68.5 [14.5] years, age range 39-91 years [4 were premenopausal at
      time of surgery]) expressed ERalpha and ERbeta protein in normal colon mucosa,
      and there were no significant differences between men and women. In tumor tissue,
      a significantly increased ERalpha protein level was observed in men (P = 0.02 vs
      normal tissue), whereas in women, the ERalpha level did not differ significantly
      between tumor and normal tissue. The level of ERbeta protein in CRC was
      significantly reduced in both men and women, but more so in men (P = 0.04 vs
      women). Furthermore, in men, the ERbeta level was significantly lower in poorly
      differentiated tumors than in moderately differentiated tumors (P < 0.03),
      whereas in women, poor differentiation of the tumor was not associated with a
      significant decrease of ERbeta level. CONCLUSIONS: Altered levels of ER subtypes
      resulting in an increased ERalpha:ERbeta ratio were found in patients with CRC.
      The observation of significantly greater alterations in men than in women
      supports the hypothesis of sex-specific differences in the pathogenesis of CRC.

PMID- 18727988
TI  - Blood oxidative stress biomarkers: influence of sex, exercise training status,
      and dietary intake.
AB  - BACKGROUND: Sex and lifestyle factors are known to influence the oxidation of
      protein, lipids, and DNA. Biomarkers such as protein carbonyls (PC),
      malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) have been commonly
      used in an attempt to characterize the oxidative status of human subjects.
      OBJECTIVE: This study compared resting blood oxidative stress biomarkers, in
      relation to exercise training status and dietary intake, between men and women.
      METHODS: Exercise-trained and sedentary men and women (with normal menstrual
      cycles; reporting during the early follicular phase) were recruited from the
      University of Memphis, Tennessee, campus and surrounding community via
      recruitment flyers and word of mouth. Participants were categorized by sex and
      current exercise training status (ie, trained or untrained). Each completed a
      detailed 5-day food record of all food and drink consumed. Diets were analyzed
      for kilocalories and macro- and micronutrient (vitamins C, E, A) intake. Venous
      blood samples were obtained at rest and analyzed for PC, MDA, and 8-OHdG.
      RESULTS: In the 131 participants (89 men, of whom 74 were exercise trained and 15
      untrained, and 42 women, of whom 22 were exercise trained and 20 untrained; mean
      [SD] age, 24 [4] years), PC did not differ significantly between trained men and
      women or between untrained men and women. However, trained participants had
      significantly lower plasma PC (measured in nmol . mg protein(-1)) (mean [SEM]
      0.0966 [0.0055]) than did untrained participants (0.1036 [0.0098]) (P < 0.05).
      MDA levels (measured in micromol . L(-1)) were significantly lower in trained
      women (0.4264 [0.0559]) compared with trained men (0.6959 [0.0593]); in trained
      men and women combined (0.5621 [0.0566]) compared with untrained men and women
      combined (0.7397 [0.0718]); and in women combined (0.5665 [0.0611]) compared with
      men combined (0.7338 [0.0789]) (P < 0.05 for all comparisons). No significant
      differences were noted between any groups for 8-OHdG. Neither PC nor 8-OHdG were
      correlated to any dietary variable, with the exception of PC and percent of
      protein in untrained men (r = 0.552; P = 0.033). MDA was positively correlated to
      protein intake and negatively correlated to percent of carbohydrate and vitamin C
      intake, primarily in trained men (P < or = 0.03). CONCLUSIONS: In this sample of
      young healthy adults, oxidative stress was lower in women than in men and in
      trained compared with untrained individuals, particularly regarding MDA. With the
      exception of MDA primarily in trained men, dietary intake did not appear to be
      correlated to biomarkers of oxidative stress.

PMID- 18727989
TI  - Influence of cardiovascular disease risk factors on the relationship between low
      bone mineral density and type 2 diabetes mellitus in a multiethnic US population
      of women and men: a cross-sectional study.
AB  - INTRODUCTION: Higher bone mineral density (BMD) has been reported among white
      women and men with type 2 diabetes mellitus (DM) compared with nondiabetic white
      individuals, but there is scant evidence for nonwhite persons. It is also not
      known whether cardiovascular disease (CVD) risk factors may confound any
      association between BMD and type 2 DM. OBJECTIVE: The present study examined the
      relationship between low BMD and type 2 DM in a multiethnic population of women
      and men while controlling for the influence of osteoporosis and CVD risk factors
      including body mass index (BMI), cigarette smoking, physical inactivity, total
      cholesterol and its components, blood pressure, and C-reactive protein. METHODS:
      Data collected from 4929 African American, Mexican American, and white women and
      men aged 50 to 79 years who participated in the household interview and clinical
      examinations during the Third National Health and Nutrition Examination Survey
      were analyzed. CVD risk factors associated with type 2 DM in this study
      population were included as covariates in gender-specific multiple logistic
      regression models assessing the relationship between type 2 DM and low BMD while
      controlling for osteoporosis risk factors. Gender- and race/ethnicity-specific
      mean BMD values at the total hip for young adults aged 20 to 29 years were used
      to establish race/ethnicity and gender-specific low BMD T-scores. RESULTS: The
      final study population included 2505 women and 2424 men. More women and men with
      type 2 DM than women and men without type 2 DM were nonwhite and had high BMI.
      Osteoporosis risk factors but not CVD risk factors were associated with low BMD
      in both women and men. Type 2 DM was not associated with low BMD among women
      (odds ratio [OR] = 0.77; 95% CI, 0.56-1.08). Based on a statistically significant
      interaction between type 2 DM status and race/ethnicity, white men with type 2 DM
      were less likely to have low BMD than were white men without type 2 DM (OR =
      0.56; 95% CI, 0.37-0.86; P = 0.01). There was no significant BMD difference
      between diabetic and nondiabetic nonwhite men. CONCLUSION: CVD risk factors did
      not appear to influence the relationship between low BMD and type 2 DM in this
      study.

PMID- 18727990
TI  - Sex-specific differences in ischemic heart failure: role of estrogen.

PMID- 18727991
TI  - Can self-rated health identify US women and men with low bone mineral density? A
      cross-sectional population study.
AB  - BACKGROUND: Despite its simplicity, self-rated health (SRH) is a significant
      dimension of health assessment, with demonstrated means to identify individuals
      at increased risk of morbidity and mortality. OBJECTIVE: The aim of the present
      study was to assess whether SRH, age, and modifiable osteoporosis risk factors in
      a hypothetical screening situation could identify individuals with low bone
      mineral density (BMD). METHODS: Data were analyzed from a multiethnic sample of
      4905 women and men aged 50 to 79 years from the Third National Health and
      Nutrition Examination Survey. Low BMD was assessed according to the World Health
      Organization definition using gender- and race/ethnicity-specific young adult
      mean values to calculate T-scores. Multiple linear regression analysis was used
      to determine whether BMD was lower among those with poorer SRH; multiple logistic
      regression analysis was used to determine whether poor SRH was associated with
      low BMD. RESULTS: The study population included 616 and 589 African American; 522
      and 564 Mexican American; and 1312 and 1302 white women and men, respectively.
      The distributions of SRH responses differed for African American and Mexican
      American women and men compared with the distributions for same-gender whites,
      with significantly more white women and men reporting excellent or very good
      health (P < 0.05) and significantly greater proportions of African American and
      Mexican American women and men reporting poorer health (P < 0.05). Among women
      and nonwhite men, there was no evidence of an association between BMD and SRH.
      Linear trends of decreasing BMD with declining SRH were detected for all men with
      low or normal body mass index (P < 0.001) and overweight men (P < 0.001). When
      stratified by race/ethnicity, a linear trend of decreasing BMD with declining SRH
      was found for nonobese white men only (P-trend: <0.001). The likelihood of having
      low BMD among nonobese white men who reported excellent or very good health was
      two-thirds that of their male counterparts with poor SRH (P < 0.001).
      CONCLUSIONS: Independent of age and modifiable osteoporosis risk factors, poor
      SRH may be a relevant risk factor for low BMD among older nonobese white men.
      Further research is needed to determine whether SRH may be a useful risk
      assessment tool for low BMD in this group of men.

PMID- 18727992
TI  - Frequency of discussing HIV prevention and care topics with patients with HIV:
      influence of physician gender, race/ethnicity, and practice characteristics.
AB  - BACKGROUND: Because people living with HIV now have greater life expectancy and
      reduced morbidity, there is a greater need for physicians to discuss HIV
      transmission risk reduction with these patients. Very limited data are available
      examining how frequently this discussion is held. OBJECTIVE: We examined the
      frequency of discussing HIV prevention and HIV care topics, as well as the
      associations of gender, race/ethnicity, and practice characteristics of
      physicians caring for persons with HIV. METHODS: In a 4-city (Miami, Atlanta,
      Baltimore, Los Angeles) survey, 417 licensed physicians who primarily cared for
      patients with HIV were mailed a 58-item questionnaire about how frequently they
      discussed HIV transmission risk reduction, adherence to HIV antiretroviral
      treatment (ART), adherence to opportunistic infection (OI) prophylaxis, and how
      to take medicines. Multivariate logistic regression analyses were used to examine
      the association between physician gender, race/ethnicity, and practice
      characteristics, and the frequency of discussing these topics. RESULTS: A total
      of 317 physicians responded to the mailed questionnaire. Less than 40% of the
      physicians reported always discussing HIV transmission risk reduction with
      patients. In contrast, 83.9% and 65.0% reported always discussing adherence to
      ART and to OI prophylaxis, respectively. Of these physicians, 65.1% strongly
      agreed or somewhat agreed that they had sufficient time to provide the care and
      information needed to their patients. In multivariate analysis, the frequency of
      discussing HIV transmission risk reduction was higher for physicians who were
      Hispanic (P = 0.03) or Asian/Pacific Islander (P = 0.001), for physicians who
      reported they had enough time to provide care and information to patients (P =
      0.003), and for physicians who cared for fewer patients (P = 0.05). The frequency
      of discussing HIV transmission risk reduction was suggestive of a higher rate for
      female physicians, but did not quite reach statistical significance. CONCLUSIONS:
      We observed a lower frequency of discussing the topic of HIV prevention compared
      with that of HIV care among the physicians surveyed. This infrequent discussion
      with patients with HIV represents a missed opportunity, and physicians should be
      encouraged to include discussion of prevention as a standard of care.

PMID- 18727993
TI  - Gender differences in health-related quality of life among healthy aged and old
      aged Austrians: cross-sectional analysis.
AB  - BACKGROUND: Although they experience lower mortality rates and lower rates of
      several chronic diseases than do their male counterparts, aging women are more
      likely to experience functional impairment in mobility and a general diminished
      health-related quality of life (HRQoL). The determinants of these gender
      differences have been the subject of controversy. OBJECTIVE: This study analyzed
      gender differences in HRQoL in relation to social and biomedical factors such as
      age, marital status, educational level, and living arrangements. METHODS:
      Participants were recruited via snowball sampling. All were healthy and lived
      independently in private homes. Data were obtained from personal interviews,
      based on a 30-item questionnaire, in the private homes of the participants.
      Additionally, HRQoL was assessed by means of the abbreviated version of the World
      Health Organization Quality of Life (WHOQOL-BREF) 26-item questionnaire, which
      contains 1 general health item, 1 general QoL item, and 24 specific items
      covering 4 broad domains: physical (DOM I), psychological (DOM II), social (DOM
      III), and environmental (DOM IV). RESULTS: The participants (98 women, 62 men)
      enrolled in the study ranged in age from 57 to 95 years (mean [SD] age: 71.8
      [8.6] years). The younger age group (aged 57-70 years) comprised 54 women and 25
      men, and the older age group (aged >70 years) comprised 44 women and 37 men.
      Women aged < or =70 years rated their health and QoL significantly higher than
      did men in the same age group (P = 0.02). These women rated physical capacity
      (DOM I), social relationships (DOM III), and environment (DOM IV) higher, but not
      statistically significantly different, than did same-aged men. Women and men
      exhibited nearly identical psychological health (DOM II) values. Physical
      capacity (DOM I) differed significantly between women and men aged >70 years (P =
      0.03). Women aged >70 years rated their QoL lower than their male counterparts
      did, although not significantly so. These women depended more on medical
      treatment, felt significantly less safe in everyday life (P = 0.03), and were
      less satisfied with themselves. The results of the multiple regression analyses
      suggest that gender may have a significant impact on general QoL for both age
      groups (P < 0.01 for the younger age group; P > 0.04 for the older age group). In
      these analyses, gender also had a significant impact on 2 domains, physical
      capacity and social relationships (P < 0.02 for both domains), among the
      participants of the younger age group. CONCLUSION: Depending on the age group (<
      or =70 vs >70 years) in this small sample of Austrian women and men, gender
      influenced HRQoL.

PMID- 18727996
TI  - An alternative method for plotting dispersion curves.
AB  - Solving the frequency equation and plotting the dispersion curves in problems of
      wave propagation in cylinders and plates, particularly when the material is
      anisotropic, are complicated tasks. The traditional numerical methods are usually
      based on determination of the zeros of the frequency equation by using an
      iterative find-root algorithm. In this paper, an alternative method is proposed
      which extracts the solution of the frequency equation in the form of dispersion
      curves from the three-dimensional illustration of the frequency equation. For
      this purpose, a three-dimensional representation of the real roots of the
      frequency equation is first plotted. The dispersion curves, which are the
      numerical solutions of the frequency equation, are then obtained by a suitable
      cut in the velocity-frequency plane. The advantages of this method include
      simplicity, high speed, low possibility of numerical error, and presentation of
      the results in a graphical form that promotes ease of interpretation. This method
      is not directly applicable to problems which incorporate high damping or leaky
      waves. However, if the damping is not very high, it could be a good estimate of
      the true dispersion curves.

PMID- 18727997
TI  - UV treatment of microorganisms on artificially-contaminated surfaces using
      excimer and microwave UV lamps.
AB  - An XeBr excilamp having a peak emission at 283 nm, and microwave UV lamps with
      peak emissions at 253.7 nm that also generate ozone, have been tested for ability
      to eradicate high populations of microbial vegetative cells and spores (of
      bacteria and fungi) artificially added to filter surfaces. The study examined the
      energy required to completely eradicate large populations on filter surfaces. It
      was found that both the excilamp and microwave UV lamps were effective at killing
      large populations on surfaces with killing efficiency dependant on the type of
      organism, and, whether present in its vegetative or spore forms. The main killing
      factor is UV radiation following short treatment times. It is considered that for
      longer irradiation periods that are required to facilitate complete destruction
      of surface microorganisms, ozone and other oxidising species produced by
      microwave UV lamps would act to enhance microbial destruction.

PMID- 18727998
TI  - Experimental and modeling study of the effect of CH(4) and pulverized coal on
      selective non-catalytic reduction process.
AB  - The reduction of nitric oxide using ammonia combined with methane and pulverized
      coal additives has been studied in a drop tube furnace reactor. Simulated flue
      gas with 1000 ppm NO(x) and 3.4% excess oxygen was generated by cylinder gas.
      Experiments were performed in the temperature range of 700-1200 degrees C to
      investigate the effects of additives on the DeNO(x) performance. Subsequently, a
      kinetic mechanism was modified and validated based on experimental results, and a
      computational kinetic modeling with CHEMKIN was conducted to analyze the
      secondary pollutants. For both methane and pulverized coal additives, the
      temperature window is shifted towards lower temperatures. The appropriate
      reaction temperature is shifted to about 900 and 800 degrees C, respectively with
      1000 ppm methane and 0.051 g min(-1) pulverized lignite coal. The addition of
      methane and pulverized coal widens the temperature window towards lower
      temperature suggesting a low temperature application of the process. Furthermore,
      selective non-catalytic reduction (SNCR) reaction rate is accelerated evidently
      with additives and the residence time to complete the reaction is shortened
      distinctly. NO(x) reduction efficiency with 80% is achieved in about 0.3s without
      additive at 1000 degrees C. However, it is achieved in only about 0.2s with 100
      ppm methane as additive, and only 0.07 and 0.05s are needed respectively for the
      cases of 500 and 1000 ppm methane. The modified kinetic modeling agrees well with
      the experimental results and reveals additional information about the process.
      Investigation on the byproducts where NO(2) and N(2)O were analyzed by modeling
      and the others were investigated by experimental means indicates that emissions
      would not increase with methane and pulverized coal additions in SNCR process and
      the efficacious temperature range of SNCR reaction is widened approximately with
      100 degrees C.

PMID- 18727999
TI  - Wastewater treatment plants (WWTPs) as a source of sediment contamination by
      toxic organic pollutants and fecal sterols in a semi-enclosed bay in Korea.
AB  - Toxic organic contaminants and a macrobenthic community were assayed in sediments
      collected near a wastewater treatment plant (WWTP) outfall to assess the impact
      of WWTP discharges on an aquatic environment. Average concentrations of toxic
      organic contaminants in sediments from 20 locations were 96.7ng TEQ/kg dry matter
      for PCDD/Fs, 1.84ng TEQ/kg dry matter for dioxin-like PCBs, 29.1microg/kg dry
      matter for PBDEs, 411microg/kg dry matter for nonylphenols, 1021microg/kg dry
      matter for fecal sterols, and 928microg/kg dry matter for PAHs. Concentrations of
      all the organic contaminants and fecal sterols varied widely and there was a
      clear decrease in concentration gradients with increasing distances from the WWTP
      outfall. This result suggests that WWTP activities contribute to contamination by
      organic chemicals. A survey of benthic organisms showed the dominance of a few
      polychaete species, indicating a deterioration of the macrobenthic community by
      the WWTP discharge. Non-parametric multidimensional scaling (MDS) ordination and
      Spearman correlation analyses showed that organic contamination is associated
      with the benthic community structure. For polychaete species, the sensitive
      species for organic contaminants was Paraprionospio pinnata, while contaminant
      tolerant species were Spiochaetopterus koreana and Capitella capitata. BIOENV
      analyses of all locations suggested PCDDs and PCDFs as the major contaminants
      influencing the structure of the macrobenthic community. The present study
      highlights that continuous WWTP discharges contribute to severe organic
      contamination and risks for the benthic community in an aquatic ecosystem.

PMID- 18728000
TI  - Inhibition of protein tyrosine phosphatase 1B and alkaline phosphatase by
      bis(maltolato)oxovanadium (IV).
AB  - Vanadate has been recognized as a specific and potent phosphatase inhibitor since
      its structure is similar to that of phosphate. In this study, we measured the
      inhibition of glutathione S-transferase-tagged protein tyrosine phosphatase 1B
      (GST-PTP1B) and alkaline phosphatase (ALP) by the insulin enhancing compounds,
      bis(maltolato)oxovanadium(IV) (BMOV). The results showed that the activity of GST
      PTP1B was reversibly inhibited by solutions of BMOV with an IC(50) value of
      0.86+/-0.02 microM. Steady state kinetic studies showed that inhibition of GST
      PTP1B by BMOV was of a mixed competitive and noncompetitive type. In addition,
      incubation of GST-PTP1B with BMOV showed a time-dependent biphasic inactivation
      of the protein. On the other hand, the inhibitory behavior of BMOV on ALP
      activity was reversible and competitive with an IC(50) value of 32.1+/-0.6
      microM. Incubation with BMOV did not show biphasic inactivation of ALP. The
      reversible inhibition of GST-PTP1B by BMOV is more potent than that of ALP, but
      solutions of BMOV inhibited both enzymes. This data support the suggestion that
      mechanisms for the inhibitory effects of BMOV on GST-PTP1B and ALP are very
      different.

PMID- 18728001
TI  - Brief dynamic therapy combined with pharmacotherapy in the treatment of major
      depressive disorder: long-term results.
AB  - BACKGROUND: There is a paucity of controlled trials examining the efficacy of
      brief dynamic psychotherapy (BDT) in the treatment of major depressive disorder,
      especially in a long-term perspective. The aim of the present study is to
      evaluate recurrence rates in unipolar major depressed patients who are responsive
      to acute phase combined treatment with BDT plus pharmacotherapy in comparison
      with patients initially treated with pharmacotherapy alone. METHODS: Subjects for
      this study were 92 patients who met criteria for remission at the end of a 6
      month acute treatment phase for major depressive disorder, single episode, with
      combined therapy (BDT plus pharmacotherapy) versus pharmacotherapy alone. 41
      (64.1%) subjects were remitters to combined treatment and 51 (61.4%) were
      remitters to antidepressants alone. The study included a 6-month continuation
      treatment trial with pharmacotherapy and a following perspective, naturalistic 48
      month follow-up (without any treatment). RESULTS: Patients who received combined
      treatment, in comparison with those who were treated with pharmacotherapy alone,
      show a significant lower rate of recurrences of depressive episodes at 48-months
      naturalistic follow up (27.5% in comparison with 46.9%: chi(2)=3.525; df=1;
      p=.048). LIMITATIONS: Inclusion and exclusion criteria may limit the
      generalizability of the results. Furthermore it may be unclear whether the effect
      is attributable to BDT per se as opposed to extra time with a therapist.
      CONCLUSIONS: The significant lower recurrence rates in a 48-month follow-up in
      the group of patients treated with the addition of BDT to medication in the acute
      phase support the view of the advantage in the long-term outcome of adding
      psychotherapeutic intervention to pharmacotherapy in the acute therapy of
      unipolar major depression.

PMID- 18728002
TI  - Estradiol regulates MICA expression in human endometrial cells.
AB  - The human endometrium undergoes cyclical changes regulated by sex hormones.
      Evidence suggests that sex hormones regulate NK cell recruitment into the uterus
      in large numbers. NKG2D is an activating receptor expressed on human NK cells,
      gammadelta and CD8 T cells. NKG2D ligands are known to be sensors of cellular
      "stress". In this study, we investigated whether sex hormones directly regulate
      expression of NKG2D ligands in the human uterus. Estradiol increased MICA
      expression on uterine epithelial cells; regulation was estrogen receptor
      dependent. Real-time PCR analysis showed that NKG2D ligands MICA and MICB were
      expressed in the human endometrium. MICA protein was detected primarily on
      epithelial cells, and greater expression was observed in immunohistochemical
      analysis of tissues from patients in the secretory phase of the menstrual cycle.
      Thus, estrogens regulate expression of MICA. These data suggest hormonal
      regulation of innate immunity and NKG2D-mediated recognition in other tissues and
      diseases where estrogen may be involved.

PMID- 18728003
TI  - Mutations M184V and Y115F in HIV-1 reverse transcriptase discriminate against
      "nucleotide-competing reverse transcriptase inhibitors".
AB  - Indolopyridones are potent inhibitors of reverse transcriptase (RT) of the human
      immunodeficiency virus type 1 (HIV-1). Although the structure of these compounds
      differs from established nucleoside analogue RT inhibitors (NRTIs), previous
      studies suggest that the prototype compound INDOPY-1 may bind in close proximity
      to the polymerase active site. NRTI-associated mutations that are clustered
      around the active site confer decreased, e.g. M184V and Y115F, or increased, e.g.
      K65R, susceptibility to INDOPY-1. Here we have studied the underlying biochemical
      mechanism. RT enzymes containing the isolated mutations M184V and Y115F cause 2-3
      fold increases in IC(50) values, while the combination of the two mutations
      causes a >15-fold increase. K65R can partially counteract these effects. Binding
      studies revealed that the M184V change reduces the affinity to INDOPY-1, while
      Y115F facilitates binding of the natural nucleotide substrate and the combined
      effects enhance the ability of the enzyme to discriminate against the inhibitor.
      Studies with other strategic mutations at residues Phe-61 and Ala-62, as well as
      the use of chemically modified templates shed further light on the putative
      binding site of the inhibitor and ternary complex formation. An abasic site
      residue at position n, i.e. opposite the 3'-end of the primer, prevents binding
      of INDOPY-1, while an abasic site at the adjacent position n+1 has no effect.
      Collectively, our findings provide strong evidence to suggest that INDOPY-1 can
      compete with natural deoxynucleoside triphosphates (dNTPs). We therefore propose
      to refer to members of this class of compounds as "nucleotide-competing RT
      inhibitors" (NcRTIs).

PMID- 18728004
TI  - Regulatory monoubiquitination of phosphoenolpyruvate carboxylase in germinating
      castor oil seeds.
AB  - Phosphoenolpyruvate carboxylase (PEPC) is a tightly regulated enzyme situated at
      the core of plant C-metabolism. Although its anaplerotic role and control by
      allosteric effectors, reversible phosphorylation, and oligomerization have been
      well documented in the endosperm of developing castor oil seeds (COS), relatively
      little is known about PEPC in germinating COS. The initial phase of COS
      germination was accompanied by elevated PEPC activity and accumulation of
      comparable amounts of pre-existing 107-kDa and inducible 110-kDa immunoreactive
      PEPC polypeptides (p107 and p110, respectively). A 440-kDa PEPC heterotetramer
      composed of an equivalent ratio of non-phosphorylated p110 and p107 subunits was
      purified from germinated COS. N-terminal microsequencing, mass spectrometry, and
      immunoblotting revealed that both subunits arose from the same gene (RcPpc3) that
      encodes the p107 subunit of a phosphorylated 410-kDa PEPC homotetramer in
      developing COS but that p110 is a monoubiquitinated form of p107. Tandem mass
      spectrometry sequencing of a diglycinated tryptic peptide identified Lys-628 as
      p110's monoubiquitination site. This residue is conserved in vascular plant PEPCs
      and is proximal to a PEP-binding/catalytic domain. Incubation with a human
      deubiquitinating enzyme (USP-2 core) converted the p110:p107 PEPC heterotetramer
      into a p107 homotetramer while significantly reducing the enzyme's K(m)(PEP) and
      sensitivity to allosteric activators (hexose-Ps, glycerol-3-P) and inhibitors
      (malate, aspartate). Monoubiquitination is a non-destructive and reversible post
      translational modification involved in the control of diverse processes such as
      transcription, endocytosis, and signal transduction. The current study
      demonstrates that tissue-specific monoubiquitination of a metabolic enzyme can
      also occur and that this modification influences its kinetic and regulatory
      properties.

PMID- 18728005
TI  - Modulation of PGC-1 coactivator pathways in brown fat differentiation through
      LRP130.
AB  - The PGC-1 coactivators are important regulators of oxidative metabolism. We
      previously demonstrated that LRP130 is a binding partner of PGC-1alpha, required
      for hepatic gluconeogenesis. LRP130 is the gene mutated in Leigh syndrome French
      Canadian variant, a rare neurodegenerative disease. The importance of LRP130 in
      other, non-hepatocyte biology remains obscure. To better understand PGC-1
      coactivator function in brown fat development, we explored the metabolic role of
      LRP130 in brown adipocyte differentiation. We show that LRP130 is preferentially
      enriched in brown fat compared with white, and induced in a PGC-1-dependent
      manner during differentiation. Despite intact PGC-1 coactivator expression, brown
      fat cells deficient for LRP130 exhibit attenuated expression of several genes
      characteristic of brown fat, including uncoupling protein 1. Oxygen consumption
      studies support a specific defect in proton leak due to attenuated uncoupling
      protein 1 expression. Notably, brown fat cell development common to both PGC-1
      coactivators is governed by LRP130. Conversely, the cAMP response controlled by
      PGC-1alpha is not regulated by LRP130. These data implicate LRP130 in brown fat
      cell development and differentiation.

PMID- 18728006
TI  - Sequestration of copper from beta-amyloid promotes selective lysis by cyclen
      hybrid cleavage agents.
AB  - Decelerated degradation of beta-amyloid (Abeta) and its interaction with synaptic
      copper may be pathogenic in Alzheimer disease. Recently, Co(III)-cyclen tagged to
      an aromatic recognition motif was shown to degrade Abeta in vitro. Here, we
      report that apocyclen attached to selective Abeta recognition motifs (KLVFF or
      curcumin) can capture copper bound to Abeta and use the Cu(II) in place of
      Co(III) to become proteolytically active. The resultant complexes interfere with
      Abeta aggregation, degrade Abeta into fragments, preventing H2O2 formation and
      toxicity in neuronal cell culture. Because Abeta binds Cu in amyloid plaques,
      apocyclen-tagged targeting molecules may be a promising approach to the selective
      degradation of Abeta in Alzheimer disease. The principle of copper capture could
      generalize to other amyloidoses where copper is implicated.

PMID- 18728007
TI  - Tyrosine residues as redox cofactors in human hemoglobin: implications for
      engineering nontoxic blood substitutes.
AB  - Respiratory proteins such as myoglobin and hemoglobin can, under oxidative
      conditions, form ferryl heme iron and protein-based free radicals. Ferryl
      myoglobin can safely be returned to the ferric oxidation state by electron
      donation from exogenous reductants via a mechanism that involves two distinct
      pathways. In addition to direct transfer between the electron donor and ferryl
      heme edge, there is a second pathway that involves "through-protein" electron
      transfer via a tyrosine residue (tyrosine 103, sperm whale myoglobin). Here we
      show that the heterogeneous subunits of human hemoglobin, the alpha and beta
      chains, display significantly different kinetics for ferryl reduction by
      exogenous reductants. By using selected hemoglobin mutants, we show that the
      alpha chain possesses two electron transfer pathways, similar to myoglobin.
      Furthermore, tyrosine 42 is shown to be a critical component of the high
      affinity, through-protein electron transfer pathway. We also show that the beta
      chain of hemoglobin, lacking the homologous tyrosine, does not possess this
      through-protein electron transfer pathway. However, such a pathway can be
      engineered into the protein by mutation of a specific phenylalanine residue to a
      tyrosine. High affinity through-protein electron transfer pathways, whether
      native or engineered, enhance the kinetics of ferryl removal by reductants,
      particularly at low reductant concentrations. Ferryl iron has been suggested to
      be a major cause of the oxidative toxicity of hemoglobin-based blood substitutes.
      Engineering hemoglobin with enhanced rates of ferryl removal, as we show here, is
      therefore likely to result in molecules better suited for in vivo oxygen
      delivery.

PMID- 18728008
TI  - Roles of Tyr122-hydrophobic cluster and K+ binding in Ca2+ -releasing process of
      ADP-insensitive phosphoenzyme of sarcoplasmic reticulum Ca2+ -ATPase.
AB  - Tyr(122)-hydrophobic cluster (Y122-HC) is an interaction network formed by the
      top part of the second transmembrane helix and the cytoplasmic actuator and
      phosphorylation domains of sarcoplasmic reticulum Ca(2+)-ATPase. We have
      previously found that Y122-HC plays critical roles in the processing of ADP
      insensitive phosphoenzyme (E2P) after its formation by the isomerization from ADP
      sensitive phosphoenzyme (E1PCa(2)) (Wang, G., Yamasaki, K., Daiho, T., and
      Suzuki, H. (2005) J. Biol. Chem. 280, 26508-26516). Here, we further explored
      kinetic properties of the alanine-substitution mutants of Y122-HC to examine
      roles of Y122-HC for Ca(2+) release process in E2P. In the steady state, the
      amount of E2P decreased so that of E1PCa(2) increased with increasing lumenal
      Ca(2+) concentration in the mutants with K(0.5) 110-320 microm at pH 7.3. These
      lumenal Ca(2+) affinities in E2P agreed with those estimated from the forward and
      lumenal Ca(2+)-induced reverse kinetics of the E1PCa(2)-E2P isomerization. K(0.5)
      of the wild type in the kinetics was estimated to be 1.5 mM. Thus, E2P of the
      mutants possesses significantly higher affinities for lumenal Ca(2+) than that of
      the wild type. The kinetics further indicated that the rates of lumenal Ca(2+)
      access and binding to the transport sites of E2P were substantially slowed by the
      mutations. Therefore, the proper formation of Y122-HC and resulting compactly
      organized structure are critical for both decreasing Ca(2+) affinity and opening
      the lumenal gate, thus for Ca(2+) release from E2PCa(2). Interestingly, when K(+)
      was omitted from the medium of the wild type, the properties of the wild type
      became similar to those of Y122-HC mutants. K(+) binding likely functions via
      producing the compactly organized structure, in this sense, similarly to Y122-HC.

PMID- 18728009
TI  - PqsD is responsible for the synthesis of 2,4-dihydroxyquinoline, an extracellular
      metabolite produced by Pseudomonas aeruginosa.
AB  - 2,4-Dihydroxyquinoline (DHQ) is an abundant extracellular metabolite of the
      opportunistic pathogen Pseudomonas aeruginosa that is secreted into growth medium
      in stationary phase to concentrations comparable with those of the Pseudomonas
      quinolone signal. Using a combination of biochemical and genetic approaches, we
      show that PqsD, a condensing enzyme in the pqs operon that is essential for
      Pseudomonas quinolone signal synthesis, accounts for DHQ formation in vivo.
      First, the anthraniloyl moiety is transferred to the active-site Cys of PqsD to
      form an anthraniloyl-PqsD intermediate, which then condenses with either malonyl
      CoA or malonyl-acyl carrier protein to produce 3-(2-aminophenyl)-3-oxopropanoyl
      CoA. This short-lived intermediate undergoes an intramolecular rearrangement to
      form DHQ. DHQ was produced by Escherichia coli coexpressing PqsA and PqsD,
      illustrating that these two proteins are the only factors necessary for DHQ
      synthesis. Thus, PqsD is responsible for the production of DHQ in P. aeruginosa.

PMID- 18728010
TI  - Small molecules can selectively inhibit ephrin binding to the EphA4 and EphA2
      receptors.
AB  - The erythropoietin-producing hepatocellular (Eph) family of receptor tyrosine
      kinases regulates a multitude of physiological and pathological processes.
      Despite the numerous possible research and therapeutic applications of agents
      capable of modulating Eph receptor function, no small molecule inhibitors
      targeting the extracellular domain of these receptors have been identified. We
      have performed a high throughput screen to search for small molecules that
      inhibit ligand binding to the extracellular domain of the EphA4 receptor. This
      yielded a 2,5-dimethylpyrrolyl benzoic acid derivative able to inhibit the
      interaction of EphA4 with a peptide ligand as well as the natural ephrin ligands.
      Evaluation of a series of analogs identified an isomer with similar inhibitory
      properties and other less potent compounds. The two isomeric compounds act as
      competitive inhibitors, suggesting that they target the high affinity ligand
      binding pocket of EphA4 and inhibit ephrin-A5 binding to EphA4 with K(i) values
      of 7 and 9 mum in enzyme-linked immunosorbent assays. Interestingly, despite the
      ability of each ephrin ligand to promiscuously bind many Eph receptors, the two
      compounds selectively target EphA4 and the closely related EphA2 receptor. The
      compounds also inhibit ephrin-induced phosphorylation of EphA4 and EphA2 in
      cells, without affecting cell viability or the phosphorylation of other receptor
      tyrosine kinases. Furthermore, the compounds inhibit EphA4-mediated growth cone
      collapse in retinal explants and EphA2-dependent retraction of the cell periphery
      in prostate cancer cells. These data demonstrate that the Eph receptor-ephrin
      interface can be targeted by inhibitory small molecules and suggest that the two
      compounds identified will be useful to discriminate the activities of EphA4 and
      EphA2 from those of other co-expressed Eph receptors that are activated by the
      same ephrin ligands. Furthermore, the newly identified inhibitors represent
      possible leads for the development of therapies to treat pathologies in which
      EphA4 and EphA2 are involved, including nerve injuries and cancer.

PMID- 18728011
TI  - rac regulates its effector phospholipase Cgamma2 through interaction with a split
      pleckstrin homology domain.
AB  - Several isoforms of phospholipase C (PLC) are regulated through interactions with
      Ras superfamily GTPases, including Rac proteins. Interestingly, of two closely
      related PLCgamma isoforms, only PLCgamma(2) has previously been shown to be
      activated by Rac. Here, we explore the molecular basis of this interaction as
      well as the structural properties of PLCgamma(2) required for activation. Based
      on reconstitution experiments with isolated PLCgamma variants and Rac2, we show
      that an unusual pleckstrin homology (PH) domain, designated as the split PH
      domain (spPH), is both necessary and sufficient to effect activation of
      PLCgamma(2) by Rac2. We also demonstrate that Rac2 directly binds to PLCgamma(2)
      as well as to the isolated spPH of this isoform. Furthermore, through the use of
      NMR spectroscopy and mutational analysis, we determine the structure of spPH,
      define the structural features of spPH required for Rac interaction, and identify
      critical amino acid residues at the interaction interface. We further discuss
      parallels and differences between PLCgamma(1) and PLCgamma(2) and the
      implications of our findings for their respective signaling roles.

PMID- 18728013
TI  - Spatial structure and pH-dependent conformational diversity of dimeric
      transmembrane domain of the receptor tyrosine kinase EphA1.
AB  - Eph receptors are found in a wide variety of cells in developing and mature
      tissues and represent the largest family of receptor tyrosine kinases, regulating
      cell shape, movements, and attachment. The receptor tyrosine kinases conduct
      biochemical signals across plasma membrane via lateral dimerization in which
      their transmembrane domains play an important role. Structural-dynamic properties
      of the homodimeric transmembrane domain of the EphA1 receptor were investigated
      with the aid of solution NMR in lipid bicelles and molecular dynamics in explicit
      lipid bilayer. EphA1 transmembrane segments associate in a right-handed parallel
      alpha-helical bundle, region (544-569)(2), through the N-terminal glycine zipper
      motif A(550)X(3)G(554)X(3)G(558). Under acidic conditions, the N terminus of the
      transmembrane helix is stabilized by an N-capping box formed by the uncharged
      carboxyl group of Glu(547), whereas its deprotonation results in a rearrangement
      of hydrogen bonds, fractional unfolding of the helix, and a realignment of the
      helix-helix packing with appearance of additional minor dimer conformation
      utilizing seemingly the C-terminal GG4-like dimerization motif A(560)X(3)G(564).
      This can be interpreted as the ability of the EphA1 receptor to adjust its
      response to ligand binding according to extracellular pH. The dependence of the
      pK(a) value of Glu(547) and the dimer conformational equilibrium on the lipid
      head charge suggests that both local environment and membrane surface potential
      can modulate dimerization and activation of the receptor. This makes the EphA1
      receptor unique among the Eph family, implying its possible physiological role as
      an "extracellular pH sensor," and can have relevant physiological implications.

PMID- 18728012
TI  - Ciliary neurotrophic factor, cardiotrophin-like cytokine, and neuropoietin share
      a conserved binding site on the ciliary neurotrophic factor receptor alpha chain.
AB  - Ciliary neurotrophic factor, cardiotrophin-like cytokine, and neuropoietin are
      members of the four-helix bundle cytokine family. These proteins signal through a
      common tripartite receptor composed of leukemia inhibitory factor receptor,
      gp130, and ciliary neurotrophic factor receptor alpha. Binding to ciliary
      neurotrophic factor receptor alpha occurs through an interaction site located at
      the C terminus of the cytokine AB loop and alphaD helix, known as site 1. In the
      present study, we have generated a model of neuropoietin and identified a
      conserved binding site for the three cytokines interacting with ciliary
      neurotrophic factor receptor alpha. To identify the counterpart of this site on
      ciliary neurotrophic factor receptor alpha, its cytokine binding domain was
      modeled, and the physicochemical properties of its surface were analyzed. This
      analysis revealed an area displaying properties complementary to the site 1 of
      ciliary neurotrophic factor, cardiotrophin-like cytokine, and neuropoietin. Based
      on our computational predictions, residues were selected for their potential
      involvement in the ciliary neurotrophic factor receptor alpha binding epitope,
      and site-directed mutagenesis was carried out. Biochemical, cell proliferation,
      and cell signaling analyses showed that Phe(172) and Glu(286) of ciliary
      neurotrophic factor receptor alpha are key interaction residues. Our results
      demonstrated that ciliary neurotrophic factor, cardiotrophin-like cytokine, and
      neuropoietin share a conserved binding site on ciliary neurotrophic factor
      receptor alpha.

PMID- 18728014
TI  - Hepatitis C virus NS5A protein down-regulates the expression of spindle gene Aspm
      through PKR-p38 signaling pathway.
AB  - Hepatitis C virus often causes persistent infection and hepatocellular carcinoma.
      Studies have demonstrated the roles of viral nonstructural protein 5A (NS5A) in
      the induction of chromosome aneuploidy, but the molecular mechanisms are not
      clear. In this study, hydrodynamics-based in vivo transfection was applied to a
      mouse system. Mouse hepatocytes that successfully expressed NS5A protein were
      isolated by laser capture microdissection. Gene expression profiles of the NS5A
      expressing hepatocytes were examined by an Affymetrix oligonucleotide microarray
      system. Aspm (abnormal spindle-like, microcephaly associated), which encodes the
      mitotic spindle protein ASPM, was identified to be differentially expressed in
      the absence and the presence of NS5A. The down-regulation of Aspm mRNA and ASPM
      protein was confirmed by real time polymerase chain reaction and Western blot
      analysis, respectively, both in mouse model systems and in viral subgenomic
      replicon and in vitro transfection culturing systems. In addition, cultured cells
      that constitutively expressed NS5A protein showed G(2)/M cell cycle block and
      chromosome aneuploidy. Overexpression of ASPM relieved the G(2)/M cell cycle
      block. Furthermore, NS5A protein repressed the promoter activity of Aspm gene in
      a dose-dependent manner. The regulatory effect was abolished when amino acid
      substitutions P2209L, T2214A, and T2217G known to interrupt the NS5A-PKR
      interaction were introduced into the NS5A protein. This indicates that the down
      regulation of Aspm expression is via the PKR-p38 signaling pathway. These results
      suggest that NS5A protein down-regulates the expression of the mitotic spindle
      protein ASPM and induces aberrant mitotic cell cycle associated with chromosome
      instability and hepatocellular carcinoma.

PMID- 18728015
TI  - Diverse functional consequences of mutations in the Na+/K+-ATPase alpha2-subunit
      causing familial hemiplegic migraine type 2.
AB  - Mutations in ATP1A2, the gene coding for the Na(+)/K(+)-ATPase alpha(2)-subunit,
      are associated with both familial hemiplegic migraine and sporadic cases of
      hemiplegic migraine. In this study, we examined the functional properties of 11
      ATP1A2 mutations associated with familial or sporadic hemiplegic migraine,
      including missense mutations (T263M, T376M, R383H, A606T, R763H, M829R, R834Q,
      R937P, and X1021R), a deletion mutant (del(K935-S940)ins(I)), and a frameshift
      mutation (S966fs). According to the Na(+)/K(+)-ATPase crystal structure, a subset
      of the mutated residues (Ala(606), Arg(763), Met(829), and Arg(834)) is involved
      in important interdomain H-bond networks, and the C terminus of the enzyme, which
      is elongated by the X1021R mutation, has been implicated in voltage dependence
      and formation of a third Na(+)-binding site. Upon heterologous expression in
      Xenopus oocytes, the analysis of electrogenic transport properties, Rb(+) uptake,
      and protein expression revealed pronounced and markedly diverse functional
      alterations in all ATP1A2 mutants. Abnormalities included a complete loss of
      function (T376M), impaired plasma membrane expression (del(K935-S940)ins(I) and
      S966fs), and altered apparent affinities for extracellular cations or reduced
      enzyme turnover (R383H, A606T, R763H, R834Q, and X1021R). In addition, changes in
      the voltage dependence of pump currents and the increased rate constants of the
      voltage jump-induced redistribution between E(1)P and E(2)P states were observed.
      Thus, mutations that disrupt distinct interdomain H-bond patterns can cause
      abnormal conformational flexibility and exert long range consequences on apparent
      cation affinities or voltage dependence. Of interest, the X1021R mutation
      severely impaired voltage dependence and kinetics of Na(+)-translocating partial
      reactions, corroborating the critical role of the C terminus of Na(+)/K(+)-ATPase
      in these processes.

PMID- 18728016
TI  - Induction of efficient energy dissipation in the isolated light-harvesting
      complex of Photosystem II in the absence of protein aggregation.
AB  - Under excess illumination, the Photosystem II light-harvesting antenna of higher
      plants has the ability to switch into an efficient photoprotective mode, allowing
      safe dissipation of excitation energy into heat. In this study, we show induction
      of the energy dissipation state, monitored by chlorophyll fluorescence quenching,
      in the isolated major light-harvesting complex (LHCII) incorporated into a solid
      gel system. Removal of detergent caused strong fluorescence quenching, which was
      totally reversible. Singlet-singlet annihilation and gel electrophoresis
      experiments suggested that the quenched complexes were in the trimeric not
      aggregated state. Both the formation and recovery of this quenching state were
      inhibited by a cross-linker, implying involvement of conformational changes.
      Absorption and CD measurements performed on the samples in the quenched state
      revealed specific alterations in the spectral bands assigned to the red forms of
      chlorophyll a, neoxanthin, and lutein 1 molecules. The majority of these
      alterations were similar to those observed during LHCII aggregation. This
      suggests that not the aggregation process as such but rather an intrinsic
      conformational transition in the complex is responsible for establishment of
      quenching. 77 K fluorescence measurements showed red-shifted chlorophyll a
      fluorescence in the 690-705 nm region, previously observed in aggregated LHCII.
      The fact that all spectral changes associated with the dissipative mode observed
      in the gel were different from those of the partially denatured complex strongly
      argues against the involvement of protein denaturation in the observed quenching.
      The implications of these findings for proposed mechanisms of energy dissipation
      in the Photosystem II antenna are discussed.

PMID- 18728017
TI  - A thermodynamic model for Nap1-histone interactions.
AB  - The yeast nucleosome assembly protein 1 (yNap1) plays a role in chromatin
      maintenance by facilitating histone exchange as well as nucleosome assembly and
      disassembly. It has been suggested that yNap1 carries out these functions by
      regulating the concentration of free histones. Therefore, a quantitative
      understanding of yNap1-histone interactions also provides information on the
      thermodynamics of chromatin. We have developed quantitative methods to study the
      affinity of yNap1 for histones. We show that yNap1 binds H2A/H2B and H3/H4
      histone complexes with low nm affinity, and that each yNap1 dimer binds two
      histone fold dimers. The yNap1 tails contribute synergistically to histone
      binding while the histone tails have a slightly repressive effect on binding. The
      (H3/H4)(2) tetramer binds DNA with higher affinity than it binds yNap1.

PMID- 18728018
TI  - Regulation of estrogen receptor-mediated long range transcription via
      evolutionarily conserved distal response elements.
AB  - Nuclear signaling by estrogens rapidly induces the global recruitment of estrogen
      receptors (ERs) to thousands of highly specific locations in the genome. Here, we
      have examined whether ER binding sites that are located distal from the
      transcription start sites of estrogen target genes are functionally relevant.
      Similar to ER binding sites near the proximal promoter region, ER binding sites
      located at distal locations are occupied by ERs after estrogen stimulation. And,
      like proximal bound ERs, ERs occupied at distal sites can recruit coactivators
      and the RNA polymerase transcription machinery and mediate specific structural
      changes to chromatin. Furthermore, ERs occupied at the distal sites are capable
      of communicating with ERs bound at the promoter region, possibly via long range
      chromosome looping. In functional analysis, disruption of the response elements
      in the distal ER binding sites abrogated ER binding and significantly reduced
      transcriptional response. Finally, sequence comparison of the response elements
      at the distal sites suggests a high level of conservation across different
      species. Together, our data indicate that distal ER binding sites are bona fide
      transcriptional enhancers that are involved in long range chromosomal
      interaction, transcription complex formation, and distinct structural
      modifications of chromatin across large genomic spans.

PMID- 18728020
TI  - B-cell involvement in chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease is a serious complication in long-term
      survivors of allogeneic hematopoietic stem cell transplantation, with several
      organ systems affected. Chronic graft-versus-host disease is an important cause
      of morbidity and mortality in allogeneic hematopoietic stem cell transplantation.
      This article reviews the pathogenesis of chronic graft-versus-host disease. In
      particularly, the role of B cells in chronic graft-versus-host disease is
      evaluated, as is evident from several studies which have investigated the
      presence of antibodies as well as studies which have analyzed B cells as a target
      for immunotherapy. Thirty autoantibodies and 5 alloantibodies have been
      identified in chronic graft-versus-host disease patients in 24 studies, and 8
      autoantibodies and 5 alloantibodies seemed to be strongly associated with chronic
      graft-versus-host disease. In addition, various studies have observed significant
      improvements in chronic graft-versus-host disease using the anti-CD20(+) antibody
      rituximab. However, it appears to be highly likely that both B cells as well as T
      cells are of major importance in chronic graft-versus-host disease. Further
      research is required to clarify the pathogenesis of chronic graft-versus-host
      disease.

PMID- 18728019
TI  - Phospholipase Cgamma2 mediates RANKL-stimulated lymph node organogenesis and
      osteoclastogenesis.
AB  - Phospholipase Cgamma2 (PLCgamma2) is an important signaling effector of multiple
      receptors in the immune system. Here we show that PLCgamma2-deficient mice
      displayed impaired lymph node organogenesis but normal splenic structure and
      Peyer's patches. Receptor activator of NF-kappaB ligand (RANKL) is a tumor
      necrosis factor family cytokine and is essential for lymph node organogenesis.
      Importantly, PLCgamma2 deficiency severely impaired RANKL signaling, resulting in
      marked reduction of RANKL-induced activation of MAPKs, p38 and JNK, but not ERK.
      The lack of PLCgamma2 markedly diminished RANKL-induced activation of NF-kappaB,
      AP-1, and NFATc1. Moreover, PLCgamma2 deficiency impaired RANKL-mediated
      biological function, leading to failure of the PLCgamma2-deficient bone marrow
      macrophage precursors to differentiate into osteoclasts after RANKL stimulation.
      Re-introduction of PLCgamma2 but not PLCgamma1 restores RANKL-mediated osteoclast
      differentiation of PLCgamma2-deficient bone marrow-derived monocyte/macrophage.
      Taken together, PLCgamma2 is essential for RANK signaling, and its deficiency
      leads to defective lymph node organogenesis and osteoclast differentiation.

PMID- 18728021
TI  - First case of gamma-thalassemia in association with a betaS allele: a pitfall in
      the neonatal screening for sickle cell disease.

PMID- 18728022
TI  - An investigation into whether deletions in 9p reflect prognosis in adult
      precursor B-cell acute lymphoblastic leukemia: a multi-center study of 381
      patients.
AB  - In acute lymphoblastic leukemia, besides age and white cell count at diagnosis,
      the cytogenetic abnormalities t(9;22)/BCR-ABL and t(4;11)/MLL-AF4 are important
      prognostic markers and are often included in the treatment stratification of
      patients with adult acute lymphoblastic leukemia. Deletions in 9p are seen in
      about 9% of cases of adult acute lymphoblastic leukemia, but their prognostic
      impact has been controversial. Cytogenetic data from 381 patients diagnosed with
      B-precursor acute lymphoblastic leukemia were reviewed. Chromosomal analysis was
      successful in 240 cases. Of these cases, 18 (8%) had abnormalities in 9p and they
      were compared with patients with normal karyotypes and patients with t(9;22)/BCR
      ABL. Patients with abnormalities of chromosome 9 showed significantly shorter
      overall survival compared with patients with normal karyotypes. In fact, overall
      survival was similar to that in the poor prognosis t(9;22)/BCR-ABL-positive
      group. Our data suggest that chromosomal abnormalities involving 9p may have a
      significant negative impact on survival in adult B-precursor acute lymphoblastic
      leukemia.

PMID- 18728023
TI  - Imatinib and leptomycin B are effective in overcoming imatinib-resistance due to
      Bcr-Abl amplification and clonal evolution but not due to Bcr-Abl kinase domain
      mutation.
AB  - Treatment with imatinib is very effective in Bcr-Abl positive leukemia. However,
      development of resistance to this drug is a common phenomenon in late stage
      disease. The Bcr-Abl protein localizes to the cytoplasm in transformed cells but
      can enter the nucleus upon treatment with imatinib. Using leptomycin B, a nuclear
      export blocker, it has been shown that reactivated nuclear Bcr-Abl kinase
      activity can induce cell death, thus presenting an interesting potential
      treatment option for imatinib resistant disease. Here we show that the
      combination of imatinib and leptomycin B effectively induces cell death in
      imatinib-resistant Ba/F3 cells which display Bcr-Abl amplification or signs of
      clonal evolution. However, no such synergism is observed in imatinib-resistant
      Ba/F3 cells carrying the T315I mutation of Bcr-Abl or those which have lost Bcr
      Abl expression. Thus, a partial inhibition of Bcr-Abl by imatinib is required for
      this approach in agreement with the proposed mode of action.

PMID- 18728024
TI  - Mobilization of peripheral blood stem cells in myeloma with either pegfilgrastim
      or filgrastim following chemotherapy.
AB  - Quality and quantity of mobilized peripheral blood stem cells determine the
      safety of tandem autologous transplants in myeloma. Using the same mobilization
      chemotherapy with DT-PACE in two consecutive protocols, robustness of stem cell
      collection and rapidity of engraftment after transplantation were assessed. We
      employed either twice a day filgrastim versus two doses of pegfilgrastim.
      Advantages of pegfilgrastim were: (i) a higher percentage of patients collected
      15x10(6)/kg in the first three days (p<0.001); (ii) the median number of CD34
      cells/kg collected on day 1 was higher (p=0.004); (iii) the median number of
      growth factor injections was 2 versus 26 (p<0.0001); (iv) post-transplantation
      neutrophil recovery was faster after first and second transplant (p<0.001) and
      (v) platelet recovery was faster after first transplant (when less stem cells
      were infused) (p=0.01). Pegfilgrastim may be considered the standard of care for
      stem cell mobilization.

PMID- 18728025
TI  - Correlation of liver iron concentration determined by R2 magnetic resonance
      imaging with serum ferritin in patients with thalassemia intermedia.

PMID- 18728026
TI  - Accumulation of hypoxia-inducible factor-1 alpha protein and its role in the
      differentiation of myeloid leukemic cells induced by all-trans retinoic acid.
AB  - BACKGROUND: The clinical activities of all-trans retinoic acid in the treatment
      of acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia, have
      triggered extensive studies aimed at defining the mechanisms by which this
      compound induces differentiation of leukemic cells. Recent studies show that
      hypoxia-inducible factor-1 alpha (HIF-1 alpha) contributes to the differentiation
      of acute myeloid leukemia cells via transcriptional activity-independent
      mechanisms. We investigated whether all-trans retinoic acid affects HIF-1 alpha
      protein and whether this has a role in all-trans retinoic acid-induced
      differentiation. DESIGN AND METHODS: The acute myeloid leukemia cell lines NB4
      and U937 were treated with all-trans retinoic acid, and HIF-1 alpha/HIF-1 beta
      mRNA and proteins were measured respectively by real-time quantitative reverse
      transcriptase polymerase chain reaction and western blotting. To investigate the
      role of HIF-1 alpha in all-trans retinoic acid-induced differentiation, NB4
      cells, U937 cells, U937 cells in which HIF-1 alpha was induced by the withdrawal
      of tetracycline and U937 cells with stable expression of specific short hairpin
      RNA against HIF-1 alpha, Runx1, C/EBP alpha and PU.1, were treated with all-trans
      retinoic acid and/or the hypoxiamimetic agent cobalt chloride (CoCl(2)). Cellular
      differentiation was evaluated by morphological criteria and myeloid
      differentiation antigens. RESULTS: all-trans retinoic acid rapidly increased
      endogenous and inducible expressed or CoCl(2)-stabilized HIF-1 alpha protein in
      leukemic cells under normoxia. Importantly, suppression of HIF-1 alpha expression
      by specific short hairpin RNA partially but significantly inhibited all-trans
      retinoic acid-induced differentiation of the U937 cell line. Reciprocally, the
      differentiation induced by all-trans retinoic acid was significantly enhanced by
      conditional HIF-1 alpha induction and HIF-1 alpha-stabilizing CoCl(2) treatment.
      Furthermore, knock-down of PU.1, Runx1 and C/EBP alpha, three transcriptional
      factors crucial for normal hematopoiesis, greatly inhibited the differentiation
      cooperation of all-trans retinoic acid and HIF-1 alpha induction. CONCLUSIONS:
      This work provides the first demonstration that HIF-1 alpha, a protein rapidly
      responsive to all-trans retinoic acid, plays a role in all-trans retinoic acid
      induced differentiation of leukemic cells. These observations shed new light on
      the molecular mechanisms underlying all-trans retinoic acid-induced
      differentiation of acute myeloid leukemia cells.

PMID- 18728027
TI  - Frequent reduction or absence of detection of the JAK2-mutated clone in JAK2V617F
      positive patients within the first years of hydroxyurea therapy.
AB  - We analyzed the effect of hydroxyurea on the JAK2V617F allelic ratio
      (%JAK2V617F), measured in purified blood granulocytes, of patients with
      polycythemia vera and essential thrombocythemia. Thirty-six patients were
      examined sequentially prior to and after start of hydroxy-urea therapy (8
      polycythemia vera, 17 essential thrombocythemia), or while remaining untreated (2
      polycythemia vera, 9 essential thrombocythemia). Hydroxyurea therapy (median
      duration: 15 months) reduced the %JAK2V617F by >30% in 13/25 patients (4
      polycythemia vera, 9 essential thrombocythemia). For 3 patients, JAK2V617F
      remained undetectable for 3-27 months. In addition, a single time point study of
      two large cohorts of patients, examined either at the time of diagnosis (99
      polycythemia vera, 178 essential thrombocythemia) or while receiving hydroxyurea
      (36 polycythemia vera, 98 essential thrombocythemia; median length of therapy: 32
      months), confirmed reduction of %JAK2V617F in the hydroxyurea-treated group (24%
      vs. 33% JAK2V617F at diagnosis, p<0.01). Prospective studies are needed to
      determine the prognostic value of reduced JAK2V617F allele burden under
      cytoreductive therapy.

PMID- 18728028
TI  - Changes in antithrombin and fibrinogen levels during induction chemotherapy with
      L-asparaginase in adult patients with acute lymphoblastic leukemia or
      lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical
      outcome: the CAPELAL study.
AB  - BACKGROUND: The effects of L-asparaginase on hemostasis during induction
      chemotherapy are less defined in adults than in children. We, therefore, studied
      the effects of L-asparaginase in adult patients. DESIGN AND METHODS: This was a
      retrospective analysis of 214 patients treated with L-asparaginase (7500 IU/m(2)
      x 6) for acute lymphoblastic leukemia or lymphoblastic lymphoma. Between day 1 of
      the induction course and discharge, clinical events, and biological and
      therapeutic modifications were reviewed. RESULTS: Antithrombin and fibrinogen
      levels were lower than 60% and 1 g/L in 71% and 73% of patients, respectively.
      Twenty thromboses occurred in 9.3% of the patients; these patients had a median
      antithrombin level of 53% (range, 21-111) at the time of the event. Forty-two
      episodes of bleeding occurred in 31 patients with a median fibrinogen level of
      1.3 g/L. Infusions of L-asparaginase were reduced or delayed in 64% of patients
      due to low fibrinogen and/or antithrombin levels. Fresh-frozen plasma,
      antithrombin and fibrinogen were infused in 31%, 41% and 52% of patients,
      respectively. The mean antithrombin and fibrinogen levels increased from 61% to
      88% and from 1 to 1.4 g/L after infusion of antithrombin or fibrinogen
      respectively, while both levels remained unchanged after the infusion of fresh
      frozen plasma. In patients who received antithrombin concentrates L-asparaginase
      injections were less frequently omitted or delayed (53% vs. 72%, p=0.005), the
      rate of thrombosis was lower (4.8% vs. 12.2%, p=0.04) and the disease-free
      survival was also reduced (p=0.05). CONCLUSIONS: This retrospective study
      suggests that antithrombin concentrates may have a beneficial effect on the
      outcome of adults treated for acute lymphoblastic leukemia with L-asparaginase;
      prospective studies are essential to confirm this hypothesis.

PMID- 18728029
TI  - Molecular characterization of three novel splicing mutations causing factor V
      deficiency and analysis of the F5 gene splicing pattern.
AB  - BACKGROUND: Factor V deficiency is a rare autosomal recessive hemorrhagic
      disorder, associated with bleeding manifestations of variable severity. In the
      present study, we investigated the molecular basis of factor V deficiency in
      three patients, and performed a comprehensive analysis of the factor V gene (F5)
      splicing pattern. DESIGN AND METHODS: Mutational screening was performed by DNA
      sequencing. Wild-type and mutant F5 mRNA were expressed by transient transfection
      in COS-1 cells, followed by reverse-transcriptase polymerase chain reaction and
      sequencing. Real-time reverse-transcriptase polymerase chain reaction was used to
      evaluate degradation of mRNA carrying premature termination codons. RESULTS:
      Mutational screening identified three hitherto unknown splicing mutations
      (IVS8+6T>C, IVS21+1G>A, and IVS24+1_+4delGTAG). Production of mutant transcripts
      in COS-1 cells demonstrated that both IVS21+1G>A and IVS24+1_+4delGTAG cause the
      activation of cryptic donor splice sites, whereas IVS8+6T>C causes exon-8
      skipping (F5-Delta 8-mRNA). Interestingly, F5-Delta 8-mRNA was also detected in
      wild-type transfected samples, human liver, platelets, and HepG2 cells,
      demonstrating that F5 exon-8 skipping takes place physiologically. Since F5-Delta
      8-mRNA bears a premature termination codons, we investigated whether this
      transcript is subjected to nonsense-mediated mRNA decay degradation. The results
      confirmed the involvement of nonsense-mediated mRNA decay in the degradation of
      F5 PTC(+) mRNA. Moreover, a comprehensive analysis of the F5 splicing pattern led
      to the identification of two in-frame splicing variants resulting from skipping
      of exons 3 and 5-6. CONCLUSIONS: The functional consequences of three splicing
      mutations leading to FV deficiency were elucidated. Furthermore, we report the
      identification of three alternatively spliced F5 transcripts.

PMID- 18728030
TI  - Allogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year
      experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).
AB  - BACKGROUND: Allogeneic stem cell transplantation is a potentially curative
      treatment for myelofibrosis, although its use is limited by a high rate of
      transplant-related mortality. In this study, we evaluated the outcome of patients
      with myelofibrosis who underwent allogeneic stem cell transplantation, and the
      impact of prognostic factors. DESIGN AND METHODS: One hundred patients were
      transplanted in 26 Italian centers between 1986 and 2006. We analyzed the
      influence of the patients' characteristics and the clinical features of their
      disease before stem cell transplantation and of transplant procedures on
      transplant-related mortality, overall survival, and relapse-free survival by
      means of univariate and multivariate analyses. RESULTS: The median age of the
      patients at the time of stem cell transplantation was 49 years (range, 21-68) and
      90% of them had an intermediate or high Dupriez score. Forty-eight percent
      received a myeloablative conditioning regimen and 78% received stem cells from
      matched sibling donors. The cumulative incidence of engraftment at day 90 after
      transplant was 87% (95% CI, 0.87-0.97). The cumulative 1-year and 3-year
      incidences of transplant-related mortality were 35% and 43%, respectively. The
      estimated 3-year overall and relapse-free survival rates after stem cell
      transplantation were 42% and 35%, respectively. In multivariate analysis,
      negative predictors of transplant-related mortality were year of stem cell
      transplantation before 1995, unrelated donor, and a long interval between
      diagnosis and transplantation. There was a trend towards longer overall and
      relapse-free survival in patients receiving peripheral blood stem cells rather
      than bone marrow as the source of their graft (p=0.070 and p=0.077,
      respectively). The intensity of the conditioning regimen (myeloablative versus
      reduced intensity regimens) did not significantly influence the outcome.
      CONCLUSIONS: We conclude that the outcome of myelofibrosis patients who underwent
      allogeneic stem cell transplantation significantly improved after 1996 due to the
      reduction in transplant-related mortality. We observed that a reduction in
      transplant-related mortality was associated with the choice of a matched sibling
      donor, whereas longer overall survival was associated with the use of peripheral
      blood as the source of stem cells.

PMID- 18728031
TI  - The effect of a novel, small non-peptidyl molecule butyzamide on human
      thrombopoietin receptor and megakaryopoiesis.
AB  - BACKGROUND: Thrombocytopenia is a common problem in the management of patients
      with cancer and other conditions that affect hematopoietic cells. In previous
      clinical trials, the polyethylene-glycol-conjugated recombinant human
      megakaryocyte growth and development factor increased platelet counts in patients
      with idiopathic thrombocytopenic purpura and solid tumors undergoing
      chemotherapy. However, antibodies to polyethylene-glycol-conjugated recombinant
      human megakaryocyte growth and development factor develop in healthy volunteers
      and patients undergoing chemotherapy and cross-react with endogenous
      thrombopoietin. As a result, clinical development of polyethylene-glycol
      conjugated recombinant human megakaryocyte growth and development factor was
      discontinued in 1998. The aim of this study was to identify an orally
      bioavailable human Mpl activator that does not develop autoantibodies against
      endogenous thrombopoietin. DESIGN AND METHODS: We screened our chemical library
      and created a novel non-peptidyl thrombopoietin receptor, Mpl activator named
      butyzamide. We evaluated the effect of butyzamide on megakaryopoiesis in vitro
      using Ba/F3 cells expressing Mpl and human hematopoietic stem cells. For the
      evaluation of its in vivo effect, we administered butyzamide orally to
      immunodeficient NOD/Shi-scid,IL-2R gamma(null) (NOG) mice transplanted with human
      fetal liver-derived CD34(+) cells and investigated the production of human
      platelets. RESULTS: Butyzamide specifically reacted with human Mpl and activated
      the same signal transduction pathway as thrombopoietin. However, unlike
      thrombopoietin, butyzamide did not react with murine Mpl and was shown to require
      the histidine residue in the transmembrane domain of Mpl for its agonistic
      activity. Butyzamide induced colony-forming unit-megakaryocytes and polyploid
      megakaryocytes from human CD34(+) hematopoietic progenitor cells, and its effects
      were comparable to those of thrombopoietin. When butyzamide was administered
      orally at the doses of 10 and 50 mg/kg for 20 days to NOG mice transplanted with
      human fetal liver-derived CD34(+) cells, the human platelet count increased by
      6.2- and 22.9-fold, respectively. CONCLUSIONS: Butyzamide is an orally
      bioavailable human Mpl activator, and appears to have potential for clinical
      development as a therapeutic agent for patients with thrombocytopenia.

PMID- 18728032
TI  - Factors that influence short-term homing of human bone marrow-derived mesenchymal
      stem cells in a xenogeneic animal model.
AB  - BACKGROUND: Human mesenchymal stem cells are potential agents for tissue
      regeneration, enhancing hematopoietic stem cell transplantation and delivering
      genes of therapeutic interest. To implement any of these strategies successfully,
      we need a better understanding of factors that influence the tissue distribution
      of systemically administered mesenchymal stem cells. DESIGN AND METHODS: The
      present study was designed to investigate the short-term tissue homing of
      mesenchymal stem cells in immunodeficient mouse models, exploring the effects of
      animal age, duration of ex vivo expansion of mesenchymal stem cells, lentiviral
      transduction and CXCR4 over-expression. Dye-labeled mesenchymal stem cells (1.5
      2.0 x 10(6)/animal) were injected via the tail vein into unconditioned
      beta2m/NOD/SCID animals. Animals were sacrificed 20-24 hours later and cell
      suspensions from tissues were examined by flow cytometry for the presence of PKH
      positive cells. RESULTS: PKH-positive cells were readily detected in the bone
      marrow, spleen, liver and lungs at 20-24 hours after infusion. The homing of
      systemically infused mesenchymal stem cells to the bone marrow and spleen of
      unconditioned beta2m/NOD/SCID animals was significantly (>2-fold, p<0.001) higher
      in younger (<10 weeks) animals, and was reduced with increasing passage number.
      Despite low surface CXCR4 expression, human mesenchymal stem cells migrated to
      SDF-1 in vitro, and this was enhanced by over-expression of CXCR4 using
      lentiviral transduction. Over-expression of CXCR4 by lentiviral transduction
      (>80%) did not alter the bone marrow homing of mesenchymal stem cells in
      unconditioned animals, but caused a significant (p<0.05) increase in homing to
      bone marrow and spleen of animals that had received prior irradiation.
      CONCLUSIONS: Tissue homing of systemically administered mesenchymal stem cells is
      influenced by host factors such as age, is diminished by prolonged in vitro
      culture, and can be increased by enforced expression of CXCR4, at least in
      irradiated hosts.

PMID- 18728034
TI  - Open heart surgery in a patient with diabetes insipidus.
AB  - Diabetes insipidus is an unusual case in patients who underwent open heart
      surgery. In this article, we aimed to present our experience of performing an
      atrial septal defect operation in a patient with diabetes insipidus who drank 30
      l of water and urinated almost the same per day.

PMID- 18728033
TI  - The effect of artificial antigen-presenting cells with preclustered anti-CD28/
      CD3/-LFA-1 monoclonal antibodies on the induction of ex vivo expansion of
      functional human antitumor T cells.
AB  - BACKGROUND: Adoptive cell therapy with ex vivo expanded autologous antitumor
      cytotoxic T lymphocytes represents an important therapeutic option as an
      anticancer strategy. In order to identify a reliable method for producing
      adequate amounts of functional antitumor cytotoxic T lymphocytes with a
      potentially long in vivo lifespan, we tested the T-cell expansion efficiency of a
      new artificial antigen-presenting cell-based system. DESIGN AND METHODS: Our
      artificial antigen-presenting cells were generated with activating (anti-CD3), co
      stimulating (anti-CD28) and adhesion (anti-LFA-1) biotinylated monoclonal
      antibodies preclustered in microdomains held on a liposome scaffold by
      neutravidin rafts. The co-localization of T-cell ligands in microdomains and the
      targeting of an adhesion protein, increasing the efficiency of immunological
      synapse formation, represent the novelties of our system. The activity of our
      artificial antigen-presenting cells was compared with that of anti-CD3/-CD28
      coated immunomagnetic microbeads and immobilized anti-CD3 monoclonal antibody
      (OKT3 clone), the only two commercially available artificial systems. RESULTS:
      Our artificial antigen-presenting cells expanded both polyclonal T cells and MART
      1-specific CD8(+) T cells in a more efficient manner than the other systems.
      Stimulation with artificial antigen-presenting cells allows for the generation of
      viable T cells displaying an immunophenotype consistent with in vivo potential
      for persistence, without increasing the frequency of regulatory T cells. The
      starting specificity of anti MART-1 CD8(+) T cells was preserved after
      stimulation with artificial antigen-presenting cells and it was statistically
      greater when compared to the activity of the same cells expanded with the other
      systems. Finally, our artificial antigen-presenting cells proved to be suitable
      for large-scale application, minimizing the volume and the costs of T-cell
      expansion. CONCLUSIONS: Our artificial antigen-presenting cells might represent
      an efficient tool to rapidly obtain a sufficient number of functional T cells for
      adoptive immunotherapy in patients with cancer.

PMID- 18728035
TI  - Congenital atresia of the left coronary artery--myocardial revascularization in
      two children.
AB  - Two patients with congenital atresia of the left coronary artery ostium underwent
      myocardial revascularization at the age of three years and three months,
      respectively. The patients were admitted to the hospital with a clinical history
      of sudden chest pain or short apnea not necessitating resuscitation. Non-invasive
      examinations and hemodynamic studies revealed dysfunction of the left ventricle
      and ostial atresia of the left coronary artery. Surgical revascularization-bypass
      grafts were performed using the left internal mammary artery and saphenous vein
      graft in the first case and the left internal mammary artery in the second child.
      Both patients survived surgery and good patency of the grafts was confirmed by
      coronary angiograms during hospital stay. These cases are interesting because of
      their rarity and diagnostic and therapeutic difficulties.

PMID- 18728036
TI  - Late thoracic pseudo-aneurysm causing collapse of vascular prostheses.
AB  - The outcome of patients with thoracic vascular prostheses is usually uneventful.
      We report two cases of collapse of thoracic vascular prostheses which occurred
      ten and forty years, respectively, after the implantation. The diagnoses were
      obtained preoperatively by CT-scan or NMR and angiography. Both patients were
      successfully treated with prosthetic replacement by an open approach.

PMID- 18728037
TI  - Effects of phosphorylcholine coating on extracorporeal circulation management and
      postoperative outcome: a double-blind randomized study.
AB  - The aim of the study was to evaluate the effects of phosphorylcholine coating
      (PC) on intra-operative extracorporeal circulation (ECC) management and
      perioperative outcome. One hundred and twenty consecutive cardiac surgery
      patients were enrolled for the study. Patients were randomly assigned to ECC with
      PC circuits (60 patients) or to corresponding non-coated circuits (60 patients).
      Trans-oxygenator pressure drop, blood flows, flow resistances and ECC parameters
      were recorded at surgery before ECC institution and every 10 min thereafter until
      ECC discontinuation. Postoperative variables (hematological parameters, drainage
      blood loss, mechanical ventilation time, incidence of atrial fibrillation, use of
      blood products) were also assessed and compared between groups. No differences
      were found between the two groups in terms of demographics, operative, and
      hematological profiles. PC showed, at equal pump flows, to significantly (P<0.01)
      attenuate pressure drop across oxygenators and to reduce oxygenator inlet
      pressures during ECC. Postoperatively, PC showed to remarkably reduce platelet
      consumption. Coating showed also to reduce postoperative blood loss, although the
      difference did not reach statistical significance. No differences between the two
      groups were found in terms of additional perioperative effects. The use of PC in
      low-risk elective cardiac surgery patients enhances ECC management, by means of a
      less restrictive trans-oxygenator blood flow.

PMID- 18728038
TI  - Low-dose aspirin may prevent growth and later surgical repair of medium-sized
      abdominal aortic aneurysms.
AB  - Experimental data suggest that aspirin-induced platelet inhibition may retard
      growth of abdominal aortic aneurysms. In this article, whether low-dose aspirin
      use is associated with reduced aneurysm progression and subsequent need for
      surgery is examined. In this observational cohort study within a screening trial,
      148 patients with small aneurysms (maximum diameter 30-48 mm) annually are
      followed. Patients were referred for surgery when the aneurysmal diameter
      exceeded 50 mm. Median follow-up time was 6.6 years. Among patients whose
      abdominal aortic aneurysms were initially 40 to 49 mm in size, the abdominal
      aortic aneurysm expansion rate for low-dose aspirin users compared with nonusers
      was 2.92 mm/y versus 5.18 mm/y (difference 2.27 mm/y, 95% CI, 0.42-4.11). No
      difference in expansion rates and risk ratios for operative repair was found for
      patients with abdominal aortic aneurysms <40 mm. For medium-sized abdominal
      aortic aneurysms, low-dose aspirin may prevent abdominal aortic aneurysm growth
      and need for subsequent repair, but residual confounding cannot be excluded.

PMID- 18728039
TI  - Shaft aneurysm of femoropopliteal expanded polytetrafluoroethylene graft treated
      with a covered stent.
AB  - Aneurysm formation is a known complication of native vein or synthetic grafts
      following peripheral bypass surgery. However, with improvement in the material
      used for prosthetic grafts, these complications are now uncommon. Open surgery
      has always been the treatment of choice for aneurysms, but the emergence of
      percutaneous endovascular intervention has led to a safer and easier way to treat
      aneurysms. In this article, a unique case of aneurysm in a reinforced expanded
      polytetrafluoroethylene graft placed 11 years ago during a femoropopliteal bypass
      surgery in a 77-year-old woman with peripheral arterial disease is presented. The
      aneurysm was treated percutaneously with a self-expanding covered stent resulting
      in complete isolation of the aneurysm with no complications encountered.

PMID- 18728040
TI  - A novel alternative to open conversion for type 1 endoleak resulting in ruptured
      aneurysm.
AB  - In this article, a novel technique for the treatment of ruptured abdominal aortic
      aneurysm secondary to proximal type 1 endoleak as a result of progressive neck
      dilatation after endovascular aneurysm repair is reported. A 74-year-old man with
      multiple comorbidities including severe ischemic heart disease, congestive
      cardiac failure, and chronic renal failure presented with a ruptured abdominal
      aortic aneurysm. He had an infrarenal endovascular aneurysm repair performed in
      1999 and had subsequently developed a proximal type 1 endoleak. At open
      laparotomy, the placement of 4 nylon ties around the infrarenal aneurysm neck to
      refashion a seal and exclude the sac from systemic pressurization effectively
      treated the rupture. In the high-risk patient, ruptured proximal type 1 endoleak
      can be successfully treated with external banding avoiding the potential
      morbidity seen with the aortic clamping and blood loss of open conversion.

PMID- 18728041
TI  - Endovascular treatment of aberrant right subclavian (lusorian) artery to
      oesophagus fistula: a case report.
AB  - The creation of a fistula between the subclavian artery and the oesophagus is
      extremely rare. All the reported cases of subclavian oesophagus-arterial fistulae
      have been described either in aberrant subclavian arteries or as caused by
      foreign bodies in the oesophagus. In this article, a case of fistulous
      communication between an aberrant right subclavian and the oesophagus managed
      with the positioning of endovascular prosthesis is presented.

PMID- 18728042
TI  - Improving subcellular localization prediction using text classification and the
      gene ontology.
AB  - MOTIVATION: Each protein performs its functions within some specific locations in
      a cell. This subcellular location is important for understanding protein function
      and for facilitating its purification. There are now many computational
      techniques for predicting location based on sequence analysis and database
      information from homologs. A few recent techniques use text from biological
      abstracts: our goal is to improve the prediction accuracy of such text-based
      techniques. We identify three techniques for improving text-based prediction: a
      rule for ambiguous abstract removal, a mechanism for using synonyms from the Gene
      Ontology (GO) and a mechanism for using the GO hierarchy to generalize terms. We
      show that these three techniques can significantly improve the accuracy of
      protein subcellular location predictors that use text extracted from PubMed
      abstracts whose references are recorded in Swiss-Prot.

PMID- 18728043
TI  - Direct mapping and alignment of protein sequences onto genomic sequence.
AB  - MOTIVATION: Finding protein-coding genes in a newly determined genomic sequence
      is the first step toward understanding the content written in the genome.
      Sequences of transcripts of homologous genes, if available, can considerably
      improve accuracy of prediction of genes and their structures, compared with that
      without such knowledge. As protein sequences are generally better conserved than
      nucleotide sequences, remote homologs can be used as templates, extending the
      applicability of evidence-based gene recognition methods. However, no tool seems
      to have been developed so far to simultaneously map and align a number of protein
      sequences on mammalian-sized genomic sequence. RESULTS: We have extended our
      computer program Spaln to accept protein sequences, as well as cDNA sequences, as
      queries. When the query and the target sequences are reasonably similar, e.g.
      between mammalian orthologs, Spaln runs one to two orders of magnitude faster
      than conventional approaches that rely on Blast search followed by dynamic
      programming-based spliced alignment. Exon-level and gene-level accuracies of
      Spaln are significantly higher than those obtained by the best available methods
      of the same type, particularly when the query and the target are distantly
      related. AVAILABILITY: Spaln is accessible online for a few species at
      http://www.genome.ist.i.kyoto-u.ac.jp/~aln_user. The source code is available for
      free for academic users from the same site.

PMID- 18728044
TI  - PathCase: pathways database system.
AB  - MOTIVATION: As the blueprints of cellular actions, biological pathways
      characterize the roles of genomic entities in various cellular mechanisms, and as
      such, their availability, manipulation and queriability over the web is important
      to facilitate ongoing biological research. RESULTS: In this article, we present
      the new features of PathCase, a system to store, query, visualize and analyze
      metabolic pathways at different levels of genetic, molecular, biochemical and
      organismal detail. The new features include: (i) a web-based system with a new
      architecture, containing a server-side and a client-side, and promoting
      scalability, and flexible and easy adaptation of different pathway databases,
      (ii) an interactive client-side visualization tool for metabolic pathways, with
      powerful visualization capabilities, and with integrated gene and organism
      viewers, (iii) two distinct querying capabilities: an advanced querying interface
      for computer savvy users, and built-in queries for ease of use, that can be
      issued directly from pathway visualizations and (iv) a pathway functionality
      analysis tool. PathCase is now available for three different datasets, namely,
      KEGG pathways data, sample pathways from the literature and BioCyc pathways for
      humans. AVAILABILITY: Available online at http://nashua.case.edu/pathways

PMID- 18728045
TI  - GOfetcher: a database with complex searching facility for gene ontology.
AB  - MOTIVATION: An important contribution to the Gene Ontology (GO) project is to
      develop tools that facilitate the creation, maintenance and use of ontologies.
      Several tools have been created for communicating and using the GO project.
      However, a limitation with most of these tools is that they suffer from lack of a
      comprehensive search facility. We developed a web application, GOfetcher, with a
      very comprehensive search facility for the GO project and a variety of output
      formats for the results. GOfetcher has three different levels for searching the
      GO: 'Quick Search', 'Advanced Search' and 'Upload Files' for searching. The
      application includes a unique search option which generates gene information
      given a nucleotide or protein accession number which can then be used in
      generating GO information. The output data in GOfetcher can be saved into several
      different formats; including spreadsheet, comma-separated values and the
      extensible markup language (XML) format. The database is available at
      http://mcbc.usm.edu/gofetcher/.

PMID- 18728046
TI  - Effects of inorganic arsenic on the rat and mouse urinary bladder.
AB  - Inorganic arsenic (arsenate and arsenite) is a known human carcinogen, inducing
      tumors of the skin, urinary bladder, and lung. Understanding the mechanism of
      inorganic arsenic carcinogenesis has been hampered by a lack of animal models. To
      define the urothelial effects of inorganic arsenic, we administered arsenate and
      arsenite in the diet or drinking water to rats and mice in several short-term
      experiments (2-10 weeks). Treatment with arsenate or arsenite in the drinking
      water or diet induced cytotoxicity and necrosis of the urothelial superficial
      layer and hyperplasia in rats and mice. Arsenate-induced changes occurred later
      in mice compared with arsenite-induced changes, but not in the rat. Hyperplasia
      in rats was evident by light microscopy at an earlier time point (2 weeks) than
      previously observed after treatment with dimethylarsinic acid (DMA(V)). The
      bromodeoxyuridine labeling index was increased in treated rats. We were unable to
      determine the bromodeoxyuridine labeling index in mice. The effects of inorganic
      arsenicals on the bladder were greater when administered in the drinking water
      than in the diet in rats and mice, but so was the overall toxicity to the animal.
      The female rat appeared more sensitive to the effects of inorganic arsenic than
      the male rat, but effects were similar in female and male mice. The mode of
      action of inorganic arsenic in rats and mice appears to involve urothelial
      cytotoxicity, increased cell proliferation and ultimately tumors. Cytotoxicity is
      likely due to the generation of reactive trivalent arsenicals excreted in the
      urine.

PMID- 18728047
TI  - Progression of hand osteoarthritis over 2 years: a clinical and radiological
      follow-up study.
AB  - OBJECTIVES: To investigate the course of hand osteoarthritis over 2 years by
      currently available outcome measures. METHODS: 189 participants of the Genetics,
      Arthrosis and Progression (GARP) study with hand osteoarthritis were followed for
      2 years. Self-reported hand pain and functional limitations were assessed with
      the Australian/Canadian osteoarthritis hand index (AUSCAN LK 3.0). Pain intensity
      upon lateral pressure in the interphalangeal and thumb base joints was graded on
      a four-point scale. Osteophytes (0-3) and joint space narrowing (JSN) (0-3) was
      scored at baseline and after 2 years in interphalangeal and thumb base joints.
      Standardised response means (SRM) were calculated. RESULTS: 172 (91%) patients
      completed the 2-year follow-up (mean age 60.5 years, 78.5% women). Statistically
      significant increases in self-reported pain and function scores, in pain
      intensity scores as well as in osteophyte and JSN total scores were seen over 2
      years. SRM were 0.25, 0.23, 0.67, 0.34 and 0.35, respectively, for self-reported
      pain and function scores, pain intensity scores, osteophyte and JSN total scores.
      Radiological progression was not associated with changes in self-reported pain
      and function. Women in an early post-menopausal stage were especially at risk of
      progressing radiologically. CONCLUSIONS: Currently available outcome measures
      were able to assess progression over the relatively short time period of 2 years.
      Radiographic outcomes were more responsive than self-reported outcomes. Pain
      intensity upon lateral pressure seems to be a responsive measure but needs
      validation.

PMID- 18728048
TI  - Evidence of epistasis between interleukin 1 and selenoprotein-S with
      susceptibility to rheumatoid arthritis.
AB  - OBJECTIVE: Selenoprotein-S (SELS) is involved in the stress response within the
      endoplasmic reticulum (ER) and inflammation. Recently, promoter variants in the
      SELS gene were shown to be associated with plasma levels of interleukin (IL)6,
      IL1beta and tumour necrosis factor (TNF). It was hypothesised that these variants
      could influence rheumatoid arthritis (RA) susceptibility and may interact with
      functional single nucleotide polymorphisms (SNPs) in the genes for IL1, IL6 and
      TNF. METHODS: Genotyping was performed in 988 unrelated healthy controls and 965
      patients with RA. Stratified analysis was used to test for interactions. Single
      gene effects and evidence of epistasis were investigated using the Mantel
      Haenszel (M-H) test and the linkage disequilibrium (LD)-based statistic. RESULTS:
      No association of SELS -105 genotype and RA susceptibility was detected.
      Stratification of SELS -105 genotypes by IL1 -511 genotypes showed that the
      disease risk (comparing AA/GA to GG at the SELS -105 locus) in individuals with
      the GG/AG genotype at the IL1beta -511 locus was significantly lower than that in
      individuals having the AA genotype at the IL1beta -511 locus (odds ratio (OR):
      0.9 and 2.3, respectively; p = 0.004 by M-H test). Significant epistasis was also
      detected using the LD-based statistic (p = <0.001). No interaction was observed
      between SELS -105 and IL6 or TNF variants. CONCLUSION: Our results reveal
      evidence of strong epistasis in two genes in the IL1 production pathway and
      highlight the potential importance of gene-gene interactions in the pathogenesis
      of RA.

PMID- 18728049
TI  - Sensitivity and specificity of the American College of Rheumatology 1987 criteria
      for the diagnosis of rheumatoid arthritis according to disease duration: a
      systematic literature review and meta-analysis.
AB  - OBJECTIVE: To evaluate the ability of the widely used ACR set of criteria (both
      list and tree format) to diagnose RA compared with expert opinion according to
      disease duration. METHODS: A systematic literature review was conducted in PubMed
      and Embase databases. All articles reporting the prevalence of RA according to
      ACR criteria and expert opinion in cohorts of early (<1 year duration) or
      established (>1 year) arthritis were analysed to calculate the sensitivity and
      specificity of ACR 1987 criteria against the "gold standard" (expert opinion). A
      meta-analysis using a summary receiver operating characteristic (SROC) curve was
      performed and pooled sensitivity and specificity were calculated with confidence
      intervals. RESULTS: Of 138 publications initially identified, 19 were analysable
      (total 7438 patients, 3883 RA). In early arthritis, pooled sensitivity and
      specificity of the ACR set of criteria were 77% (68% to 84%) and 77% (68% to 84%)
      in the list format versus 80% (72% to 88%) and 33% (24% to 43%) in the tree
      format. In established arthritis, sensitivity and specificity were respectively
      79% (71% to 85%) and 90% (84% to 94%) versus 80% (71% to 85%) and 93% (86% to
      97%). The SROC meta-analysis confirmed the statistically significant differences,
      suggesting that diagnostic performances of ACR list criteria are better in
      established arthritis. CONCLUSION: The specificity of ACR 1987 criteria in early
      RA is low, and these criteria should not be used as diagnostic tools. Sensitivity
      and specificity in established RA are higher, which reflects their use as
      classification criteria gold standard.

PMID- 18728050
TI  - Incidence and risk factors of retinopathy of prematurity in a tertiary eye
      hospital in Tehran.
AB  - AIM: To determine the incidence and risk factors of retinopathy of prematurity
      (ROP) in premature infants referred to a tertiary eye hospital during 2003-7 to
      provide preliminary evidence about ROP in Iran. METHODS: In a cross-sectional
      study, data for premature infants screened for ROP in Farabi Eye Hospital
      including possible risk factors and eye exams' results were recorded and analysed
      using chi(2), univariate and multiple regressions. Severe ROP was defined as ROP
      needing treatment or stage 4 or 5 of ROP. RESULTS: Among 953 premature infants,
      there were 329 (34.5%) different stages of ROP. Severe ROP was seen in 22.6%
      (215/953) of infants (16.5%: treatable, 6.1%: advanced untreatable). The mean
      gestational age (GA) and birth weight (BW) of infants with severe ROP were 28.8
      (SD 2.4) weeks and 1256 (389) g respectively. Univariate analysis showed a
      significant relation between GA, BW, oxygen therapy, blood transfusion and ROP
      (p<0.001), while multiple-regression methods showed GA, BW and oxygen therapy as
      independent predictors of ROP (p<0.001, 0.019 and 0.033, respectively).
      CONCLUSION: The authors observed a relatively high incidence of ROP in this
      series, especially its severe form affecting relatively more mature infants,
      which merits further investigation. GA, BW and oxygen therapy were independent
      ROP determinants.

PMID- 18728051
TI  - Surgical and visual outcomes for posterior polar cataract.
AB  - AIMS: The aims of this study were to report the surgical and visual outcomes of
      posterior polar cataract and to assess the risk factors for posterior capsule
      rupture. METHOD: Medical records of 81 eyes of 59 patients were reviewed. The
      surgical procedure used, intraoperative complications and postoperative visual
      outcome were recorded. RESULTS: Of the 81 eyes, 61 eyes (75%) underwent
      phacoemulsification. Seventeen eyes had extra-capsular cataract extraction, and
      manual small incision cataract surgery was performed on three eyes. Posterior
      capsule rupture occurred in 25 (31%) eyes: it was more common in young patients
      (<40 years) and in the extra-capsular cataract extraction group. Two eyes had
      nucleus drop during phacoemulsification. The postoperative visual acuity was
      >or=20/30 in 76 eyes. CONCLUSION: Posterior capsule rupture occurred more
      frequently in extra-capsular cataract extraction compared with
      phacoemulsification and in patients below 40 years of age. Phacoemulsification,
      done carefully, leads to good visual outcome.

PMID- 18728052
TI  - Acute posterior multifocal placoid pigment epitheliopathy following varicella
      vaccination.

PMID- 18728053
TI  - A cleaning solution for silicone intraocular lenses: "sticky silicone oil".
AB  - AIM: The aim of the study was to compare the efficacy of perfluorobutylpentane
      (F4H5) and perfluorohexyloctane (F6H8) in dissolving silicone oil from the
      surface of silicone intraocular lenses (IOL). METHODS: Droplets of stained
      silicone oil were applied to an object slide either lying flat or tilted by 30
      degrees . Mixing with H(2)O, F4H5 or F6H8 was documented by a digital camera.
      Droplets of silicone oil were applied to silicone lenses and washed off by
      repeated rinsing with F4H5 or F6H8. The silicone lenses of 11 patients with
      silicone oil remnants on the posterior IOL surface were rinsed intraoperatively
      with F4H5 during removal surgery. RESULTS: Only F4H5 was able to mix with
      silicone oil and to remove it form the surface of a glass object slides. Rinsing
      with 25 mul F4H5 reduced the amount of silicone oil 1000 mPas or 5000 mPas
      attached on a silicone lens to 15% and 28%, respectively. A hanging droplet of
      silicone oil 5000 beneath a silicone lens was completely removed from below by
      F4H5. In all patients sufficient IOL cleaning was possible using F4H5. There was
      no significant postoperative inflammation in the vitreous or anterior chamber.
      CONCLUSION: Polydimethylsiloxanes dissolve effectively in F4H5 due to its
      lipophilic chemical structure. A much smaller volume of F4H5 than F6H8 is able to
      remove silicone oil from silicone lenses completely. Intraocular use of F4H5 is
      safe, and initial clinical data underlines its effectiveness as a cleaning agent
      after contact of silicone lenses with silicone oil.

PMID- 18728054
TI  - Decreased exercise blood pressure in older adults after exercise training:
      contributions of increased fitness and decreased fatness.
AB  - OBJECTIVE: To describe the contribution of changes in fitness and fatness
      resulting from exercise training on changes in submaximal exercise blood pressure
      (BP) during treadmill testing. DESIGN AND SETTING: Prospective, randomised,
      controlled trial. PARTICIPANTS: Sedentary older adults (n = 115) with untreated
      prehypertension or mild hypertension. INTERVENTION: Six-month supervised aerobic
      and strength training. MAIN OUTCOME MEASUREMENT: Systolic BP (SBP) was assessed
      at rest and during each stage of a maximal graded exercise test (GXT) that
      determined Vo(2)peak. General and regional fatness was assessed by anthropometry,
      dual-energy x-ray absorptiometry and MRI. BP changes were calculated for each GXT
      stage, and multivariate regression models were used to describe the association
      of changes in exercise BP with changes in fitness and fatness. RESULTS: After
      training, exercisers versus controls had significantly increased Vo(2)peak and
      significantly lower measures of general and regional fatness. Also, stage
      specific SBP was significantly lower at stage 3 (-9.4 vs -1.6 mm Hg, p = 0.03)
      and stage 4 (-7.9 vs -1.2 mm Hg, p = 0.03). Pooled regression analysis across all
      stages showed that exercisers had a 7.1 mm Hg reduction in SBP, but this
      reduction fell short of statistical significance (p = 0.12) compared with
      controls. A 1.0 ml/kg/min increase in Vo(2)peak and a 1.0 cm decrease in waist
      circumference independently predicted a 1.0 mm Hg decrease in exercise SBP (p =
      0.04 and p = 0.001, respectively). CONCLUSIONS: Decreased exercise SBP was
      independently associated with decreased waist circumference, a marker of
      abdominal obesity and increased fitness. These findings suggest that exercise
      training improves multiple factors that have an independent influence on SBP.

PMID- 18728055
TI  - Relationship between knee joint laxity and knee joint mechanics during the
      menstrual cycle.
AB  - BACKGROUND: An increase in knee laxity during the menstrual cycle may increase
      the risk of anterior cruciate ligament injury. OBJECTIVE: To investigate whether
      changing knee laxity during the menstrual cycle correlates with changing knee
      joint loads in a cutting manoeuvre. DESIGN: Cross-sectional study. SETTING:
      Laboratory testing. PARTICIPANTS: 25 healthy women, with a normal menstrual
      cycle, no history of oral contraceptive use, and no previous knee injury
      INTERVENTIONS: Serum hormone concentrations were assessed and knee joint laxity
      at a load of 89 N was measured during the follicular, ovulation and luteal
      phases. Participants performed 10 trials of a cutting manoeuvre to quantify knee
      joint mechanics at each test session. MAIN OUTCOME MEASUREMENTS: Knee joint
      laxity (mm), peak knee angle ( degrees ) and knee joint moment (Nm) and knee
      joint impulse (Nms). RESULTS: Increased knee laxity was observed during ovulation
      compared with the luteal phase, but no significant changes in knee mechanics
      corresponding to menstrual phases were found. A positive correlation was found
      between changes in knee laxity and changes in knee joint loads (Deltamoment or
      Deltaimpulse) from the follicular phase to ovulation, and from ovulation to the
      luteal phase (p<0.05). Women in whom knee laxity increased showed increased knee
      loads, and those in whom knee laxity decreased showed decreased knee loads during
      the menstrual cycle. CONCLUSIONS: Knee laxity correlates positively with knee
      joint loads, and increased knee laxity during the menstrual cycle may be a
      potential risk factor for anterior cruciate ligament injuries in certain women
      during sports activity.

PMID- 18728056
TI  - The cardiovascular risk factor, soluble CD40 ligand (CD154), but not soluble CD40
      is lowered by ultra-endurance exercise in athletes.
AB  - BACKGROUND: Soluble CD40 ligand (sCD40L) is a powerful marker of cardiovascular
      risk. Exercise is known to decrease cardiovascular risk, but the impact of ultra
      endurance exercise on sCD40L responses is unknown. OBJECTIVE: To examine the
      relationship between ultra-endurance exercise in trained athletes and levels of
      sCD40L and its natural ligand sCD40. DESIGN: Control-trial, crossover design,
      exercise intervention study of sCD40L and sCD40 levels. SETTING: Outdoor exercise
      and laboratory testing, single centre study, School of Physical Education,
      University of Otago, New Zealand. PARTICIPANTS: Nine trained ultra-endurance
      athletes. INTERVENTIONS: Athletes exercised (cycled and jogged) for 17 of 24 h.
      Venous blood was sampled at baseline and serially throughout exercise and 24 and
      48 h after exercise. The athletes completed a 24 h control trial on a separate
      occasion, in randomised order. MAIN OUTCOME MEASUREMENTS: Mean levels of sCD40L
      and sCD40 during exercise and rest with 95% CIs. RESULTS: sCD40L levels dropped
      steadily from baseline (median 4128 pg/ml) to a measured nadir at 24 h following
      exercise (median 1409 pg/ml) (p=0.01). The levels had started to rise again by 48
      h after exercise. When measured as a group, sCD40L levels remained constant
      during a control rest period. sCD40 levels remained constant on both exercise and
      control days. CONCLUSION: Ultra-endurance exercise lowers the levels of the
      cardiovascular risk marker sCD40L in athletes. These results raise the
      possibility that exercise-induced changes in sCD40L may provide one of the
      mechanisms by which exercise lowers cardiovascular risk.

PMID- 18728057
TI  - Some contributions of the Department of Veterans Affairs to the epidemiology of
      multiple sclerosis.
AB  - The first class 1 treatment trial ever conducted in multiple sclerosis (MS) was a
      Veterans Administration Cooperative Study. This led us to explore MS in the
      military-veteran populations of the United States in three main series: Army men
      hospitalized with final diagnoses of MS in World War II, all veterans of World
      War II and the Korean Conflict, and veterans of later service up to 1994. In each
      series, all cases had been matched with pre-illness military peers. These series
      provide major information on its clinical features, course and prognosis,
      including survival, by sex and race (white men and women; black men), as well as
      risk factors for occurrence, course, and survival. They comprise the only
      available nationwide morbidity distributions of MS in the United States. Veterans
      who are service-connected for MS by the Department of Veterans Affairs and
      matched with their military peers remain a unique and currently available
      resource for further clinical and epidemiological study of this disease.

PMID- 18728058
TI  - A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis.
AB  - A sixth month phase II multicenter-pilot trial with a low dose of the opiate
      antagonist Naltrexone (LDN) has been carried out in 40 patients with primary
      progressive multiple sclerosis (PPMS). The primary end points were safety and
      tolerability. Secondary outcomes were efficacy on spasticity, pain, fatigue,
      depression, and quality of life. Clinical and biochemical evaluations were
      serially performed. Protein concentration of beta-endorphins (BE) and mRNA levels
      and allelic variants of the mu-opiod receptor gene (OPRM1) were analyzed. Five
      dropouts and two major adverse events occurred. The remaining adverse events did
      not interfere with daily living. Neurological disability progressed in only one
      patient. A significant reduction of spasticity was measured at the end of the
      trial. BE concentration increased during the trial, but no association was found
      between OPRM1 variants and improvement of spasticity. Our data clearly indicate
      that LDN is safe and well tolerated in patients with PPMS.

PMID- 18728059
TI  - Relationship of cognitive impairment to psychiatric symptoms in multiple
      sclerosis.
AB  - Psychiatric and cognitive changes are common in patients with multiple sclerosis
      (MS), but their relationship has not received much attention. We studied the
      relationship between psychiatric symptoms and verbal memory, working memory, and
      mental speed in 78 patients with MS and 40 healthy control subjects using linear
      regression analyses. The MS group exhibited impaired performance on all cognitive
      tests. Apathy was associated with intrusions and depression with impaired memory
      and mental speed. The association between apathy and intrusions supports the
      hypothesis that lesions in frontal areas or frontal connections contribute to a
      specific neuropsychiatric syndrome in patients with MS.

PMID- 18728060
TI  - Comorbidity, socioeconomic status and multiple sclerosis.
AB  - OBJECTIVE: Multiple sclerosis (MS) is associated with substantial morbidity. The
      impact of comorbidity on MS is unknown, but comorbidity may explain some of the
      unpredictable progression. Comorbidity is common in the general population, and
      is associated with adverse health outcomes. To begin understanding the impact of
      comorbidity on MS, we need to know the breadth, type, and frequencies of
      comorbidities among MS patients. Using the North American Research Committee on
      Multiple Sclerosis (NARCOMS) Registry, we aimed to describe comorbidities and
      their demographic predictors in MS. METHODS: In October 2006, we queried NARCOMS
      participants regarding physical comorbidities. Of 16,141 participants meeting the
      inclusion criteria, 8983 (55.7%) responded. RESULTS: Comorbidity was relatively
      common; if we considered conditions which are very likely to be accurately self
      reported, then 3280 (36.7%) reported at least one physical comorbidity. The most
      frequently reported comorbidities were hypercholesterolemia (37%), hypertension
      (30%), and arthritis (16%). Associated with the risk of comorbidity were being
      male [females vs. males, odds ratio (OR) 0.77; 0.69-0.87]; age (age >60 years vs.
      age < or = 44 years, OR 5.91; 4.95-7.06); race (African Americans vs. Whites, OR
      1.46; 1.06-2.03); and socioeconomic status (Income <$15,000 vs. Income >$100,000,
      OR 1.37; 1.10-1.70). CONCLUSIONS: Comorbidity is common in MS and similarly
      associated with socioeconomic status.

PMID- 18728061
TI  - Recurrent leukoencephalopathy with microhemorrhages: gradient-echo MRI study
      diagnostic value in CNS primary angiitis.
AB  - Diagnosis of primary angiitis of the central nervous system (PACNS) is difficult
      in relation to variability in its clinical manifestations and absence of specific
      signs in neuroimaging. A young patient presented with a recurrent encephalopathic
      clinical course. T2 and fluid-attenuated inversion recovery-magnetic resonance
      imaging (FLAIR-MRI) showed hyperintense lesions in the cerebral white matter
      suggesting demyelination. Those lesions decreased or even disappeared after
      treatment with steroids and immunoglobulins. In echo gradient MRI (T2*-MRI),
      there were permanent cortical-subcortical petechial hypointense lesions
      (microhemorrhages). Definite diagnosis was established after cerebral biopsy.
      Intravenous cyclophosphamide was administrated with no new relapses in more than
      18 months of follow-up. In a compatible clinical course, the finding of petechial
      hemorrhages in T2*-WI could play an important role in early diagnosis of PACNS.

PMID- 18728063
TI  - Abstracts of the World Congress on Treatment and Research in Multiple Sclerosis,
      September 17-20, 2008, Montreal, Canada.

PMID- 18728064
TI  - Carotid ultrasound in children: a window to arterial ageing.

PMID- 18728065
TI  - Sudden cardiac death and left ventricular ejection fraction during long-term
      follow-up after acute myocardial infarction in the primary percutaneous coronary
      intervention era: results from the HIJAMI-II registry.
AB  - OBJECTIVE: To determine the incidence of sudden cardiac death (SCD) according to
      left ventricular ejection fraction (LVEF) in survivors of myocardial infarction
      (MI) in the primary percutaneous coronary intervention (PCI) era. DESIGN: A
      multicentre observational prospective registered cohort study. SETTING: 18
      medical centres in Japan. PATIENTS: 4122 consecutive patients (mean age 66 (SD
      12) years, 73.7% male) with acute MI, who were discharged alive. MAIN OUTCOME
      MEASURES: The primary end-point was SCD, and a secondary end-point was death from
      any cause. RESULTS: Patients were categorised into three groups: LVEF >40% (n =
      3416), LVEF < or =40% and >30% (n = 507) and LVEF < or =30% (n = 199). Among all
      patients, 77.8% received PCI and 3.7% received coronary artery bypass graft
      surgery. During an average follow-up of 4.1 years, SCD was 1.2% and mortality was
      13.1%. Patients with LVEF < or =30% and LVEF < or =40% and >30% were at increased
      risk for SCD (HR 5.99, 95% CI 2.73 to 13.14, p<0.001, HR 3.37, 95% CI 1.74 to
      6.50, p<0.001, respectively), and mortality (HR 3.85, 95% CI 2.96 to 5.00,
      p<0.001, HR 2.06, 95% CI 1.66 to 2.57, p<0.001, respectively), compared to
      patients with LVEF >40%. Kaplan-Meier estimates of SCD in patients with LVEF < or
      =30% were 2.9%, 5.1% and 5.1% at 1, 3 and 5 years, respectively. CONCLUSION:
      There is a low incidence of SCD in survivors of MI in the primary PCI era,
      although LVEF is a predictor of increased risk for SCD.

PMID- 18728066
TI  - British Cardiovascular Society: international guideline review.

PMID- 18728067
TI  - NICE guidelines for the use of drug-eluting stents: how do we establish worth?

PMID- 18728068
TI  - Stenting the paediatric heart.

PMID- 18728069
TI  - Non-invasive gene-expression-based detection of well-developed collateral
      function in individuals with and without coronary artery disease.
AB  - BACKGROUND: In patients with coronary artery disease (CAD), a well grown
      collateral circulation has been shown to be important. The aim of this
      prospective study using peripheral blood monocytes was to identify marker genes
      for an extensively grown coronary collateral circulation. METHODS: Collateral
      flow index (CFI) was obtained invasively by angioplasty pressure sensor guidewire
      in 160 individuals (110 patients with CAD, and 50 individuals without CAD). RNA
      was extracted from monocytes followed by microarray-based gene-expression
      analysis. 76 selected genes were analysed by real-time polymerase chain reaction
      (PCR). A receiver operating characteristics analysis based on differential gene
      expression was then performed to separate individuals with poor (CFI<0.21) and
      well-developed collaterals (CFI>or=0.21) Thereafter, the influence of the
      chemokine MCP-1 on the expression of six selected genes was tested by PCR.
      RESULTS: The expression of 203 genes significantly correlated with CFI (p =
      0.000002-0.00267) in patients with CAD and 56 genes in individuals without CAD (p
      = 00079-0.0430). Biological pathway analysis revealed 76 of those genes belonging
      to four different pathways: angiogenesis, integrin-, platelet-derived growth
      factor-, and transforming growth factor beta-signalling. Three genes in each
      subgroup differentiated with high specificity among individuals with low and high
      CFI (>or=0.21). Two out of these genes showed pronounced differential expression
      between the two groups after cell stimulation with MCP-1. CONCLUSIONS: Genetic
      factors play a role in the formation and the preformation of the coronary
      collateral circulation. Gene expression analysis in peripheral blood monocytes
      can be used for non-invasive differentiation between individuals with poorly and
      with well grown collaterals. MCP-1 can influence the arteriogenic potential of
      monocytes.

PMID- 18728071
TI  - Further delineation of Pitt-Hopkins syndrome: phenotypic and genotypic
      description of 16 novel patients.
AB  - BACKGROUND: Haploinsufficiency of the gene encoding for transcription factor 4
      (TCF4) was recently identified as the underlying cause of Pitt-Hopkins syndrome
      (PTHS), an underdiagnosed mental-retardation syndrome characterised by a distinct
      facial gestalt, breathing anomalies and severe mental retardation. METHODS: TCF4
      mutational analysis was performed in 117 patients with PTHS-like features.
      RESULTS: In total, 16 novel mutations were identified. All of these proven
      patients were severely mentally retarded and showed a distinct facial gestalt. In
      addition, 56% had breathing anomalies, 56% had microcephaly, 38% had seizures and
      44% had MRI anomalies. CONCLUSION: This study provides further evidence of the
      mutational and clinical spectrum of PTHS and confirms its important role in the
      differential diagnosis of severe mental retardation.

PMID- 18728070
TI  - Autistic phenotypes and genetic testing: state-of-the-art for the clinical
      geneticist.
AB  - Autism spectrum disorders represent a group of developmental disorders with
      strong genetic underpinnings. Several cytogenetic abnormalities or de novo
      mutations able to cause autism have recently been uncovered. In this study, the
      literature was reviewed to highlight genotype-phenotype correlations between
      causal gene mutations or cytogenetic abnormalities and behavioural or
      morphological phenotypes. Based on this information, a set of practical
      guidelines is proposed to help clinical geneticists pursue targeted genetic
      testing for patients with autism whose clinical phenotype is suggestive of a
      specific genetic or genomic aetiology.

PMID- 18728073
TI  - Intragenomic variation of fungal ribosomal genes is higher than previously
      thought.
AB  - Nuclear ribosomal genes in most eukaryotes are present in multiple copies and
      often used for taxonomic and phylogenetic analyses. We comprehensively examined
      intragenomic polymorphism levels of three nuclear ribosomal loci for four
      important plant pathogenic fungi by polymerase chain reaction amplification and
      cloning. Here, we show that single nucleotide polymorphisms are present in an
      unexpectedly high amount. This might have implications for studies of fungal
      evolution, phylogenetics, and population genetics. Furthermore, our work
      demonstrates that the majority of all ribosomal sequences obtained from one
      individual and gene is identical to the majority rule consensus sequence of all
      detected sequence variants. Due to the large number of polymorphisms found and
      the fact that the polymorphism level differed markedly even between ribosomal
      genes of one and the same individual, we assume that nuclear ribosomal genes
      might not always evolve in a strictly concerted manner.

PMID- 18728072
TI  - Refinement of cortical dysgeneses spectrum associated with TUBA1A mutations.
AB  - OBJECTIVE: We have recently shown that de novo mutations in the TUBA1A gene are
      responsible for a wide spectrum of neuronal migration disorders. To better define
      the range of these abnormalities, we searched for additional mutations in a
      cohort of 100 patients with lissencephaly spectrum for whom no mutation was
      identified in DCX, LIS1 and ARX genes and compared these data to five previously
      described patients with TUBA1A mutations. RESULTS: We detected de novo TUBA1A
      mutations in six patients and highlight the existence of a prominent form of
      TUBA1A related lissencephaly. In four patients, the mutations identified,
      c.1190T>C (p.L397P), c.1265G>A (p.R422H), c.1264C>T (p.R422C), c.1306G>T
      (p.G436R), have not been reported before and in two others, the mutation
      corresponds to a recurrent missense mutation, c.790C>T (p.R264C), likely to be a
      hot spot of mutation. All together, it emerges that the TUBA1A related
      lissencephaly spectrum ranges from perisylvian pachygyria, in the less severe
      form, to posteriorly predominant pachygyria in the most severe, associated with
      dysgenesis of the anterior limb of the internal capsule and mild to severe
      cerebellar hypoplasia. When compared with a large series of lissencephaly of
      other origins (ILS17, ILSX or unknown origin), these features appear to be
      specific to TUBA1A related lissencephaly. In addition, TUBA1A mutated patients
      share a common clinical phenotype that consists of congenital microcephaly,
      mental retardation and diplegia/tetraplegia. CONCLUSIONS: Our data highlight the
      presence of consistent and specific abnormalities that should allow the
      differentiation of TUBA1A related lissencephalies from those related to LIS1, DCX
      and ARX genes.

PMID- 18728075
TI  - FDA says that bisphenol A in food is safe, despite controversy.

PMID- 18728074
TI  - Multiple paleopolyploidizations during the evolution of the Compositae reveal
      parallel patterns of duplicate gene retention after millions of years.
AB  - Of the approximately 250,000 species of flowering plants, nearly one in ten are
      members of the Compositae (Asteraceae), a diverse family found in almost every
      habitat on all continents except Antarctica. With an origin in the mid Eocene,
      the Compositae is also a relatively young family with remarkable diversifications
      during the last 40 My. Previous cytologic and systematic investigations suggested
      that paleopolyploidy may have occurred in at least one Compositae lineage, but a
      recent analysis of genomic data was equivocal. We tested for evidence of
      paleopolyploidy in the evolutionary history of the family using recently
      available expressed sequence tag (EST) data from the Compositae Genome Project.
      Combined with data available on GenBank, we analyzed nearly 1 million ESTs from
      18 species representing seven genera and four tribes. Our analyses revealed at
      least three ancient whole-genome duplications in the Compositae-a
      paleopolyploidization shared by all analyzed taxa and placed near the origin of
      the family just prior to the rapid radiation of its tribes and independent genome
      duplications near the base of the tribes Mutisieae and Heliantheae. These results
      are consistent with previous research implicating paleopolyploidy in the
      evolution and diversification of the Heliantheae. Further, we observed parallel
      retention of duplicate genes from the basal Compositae genome duplication across
      all tribes, despite divergence times of 33-38 My among these lineages. This
      pattern of retention was also repeated for the paleologs from the Heliantheae
      duplication. Intriguingly, the categories of genes retained in duplicate were
      substantially different from those in Arabidopsis. In particular, we found that
      genes annotated to structural components or cellular organization Gene Ontology
      categories were significantly enriched among paleologs, whereas genes associated
      with transcription and other regulatory functions were significantly
      underrepresented. Our results suggest that paleopolyploidy can yield strikingly
      consistent signatures of gene retention in plant genomes despite extensive
      lineage radiations and recurrent genome duplications but that these patterns vary
      substantially among higher taxonomic categories.

PMID- 18728077
TI  - End of the free lunch?

PMID- 18728079
TI  - Palliative care in Scotland is too focused on cancer, says national report.

PMID- 18728080
TI  - Poor economy means more Americans have trouble paying medical bills.

PMID- 18728081
TI  - Complications of type 1 diabetes in adolescents.

PMID- 18728082
TI  - Role of blood pressure in development of early retinopathy in adolescents with
      type 1 diabetes: prospective cohort study.
AB  - OBJECTIVE: To examine the relation between blood pressure and the development of
      early retinopathy in adolescents with childhood onset type 1 diabetes. DESIGN:
      Prospective cohort study. SETTING: Diabetes Complications Assessment Service at
      the Children's Hospital at Westmead, Sydney, Australia. PARTICIPANTS: 1869
      patients with type 1 diabetes (54% female) screened for retinopathy with baseline
      median age 13.4 (interquartile range 12.0-15.2) years, duration 4.9 (3.1-7.0)
      years, and albumin excretion rate of 4.4 (3.1-6.8) microg/min plus a subgroup of
      1093 patients retinopathy-free at baseline and followed for a median 4.1 (2.4
      6.6) years. MAIN OUTCOME MEASURES: Early background retinopathy; blood pressure.
      RESULTS: Overall, retinopathy developed in 673 (36%) participants at any time
      point. In the retinopathy-free group, higher systolic blood pressure (odds ratio
      1.01, 95% confidence interval 1.003 to 1.02) and diastolic blood pressure (1.01,
      1.002 to 1.03) were predictors of retinopathy, after adjustment for albumin
      excretion rate (1.27, 1.13 to 1.42), haemoglobin A(1c) (1.08, 1.02 to 1.15),
      duration of diabetes (1.16, 1.13 to 1.19), age (1.13, 1.08 to 1.17), and height
      (0.98, 0.97 to 0.99). In a subgroup of 1025 patients with albumin excretion rate
      below 7.5 microg/min, the cumulative risk of retinopathy at 10 years' duration of
      diabetes was higher for those with systolic blood pressure on or above the 90th
      centile compared with those below the 90th centile (58% v 35%, P=0.03). The risk
      was also higher for patients with diastolic blood pressure on or above the 90th
      centile compared with those below the 90th centile (57% v 35%, P=0.005).
      CONCLUSIONS: Both systolic and diastolic blood pressure are predictors of
      retinopathy and increase the probability of early retinopathy independently of
      incipient nephropathy in young patients with type 1 diabetes.

PMID- 18728083
TI  - Failure to replicate two mate preference QTLs across multiple strains of
      Drosophila pseudoobscura.
AB  - Behavioral genetic mapping studies in model organisms predominantly use crosses
      originating from a single pair of inbred lines to determine the location of
      alleles that confer genetic variation in the trait of interest, and they often
      make sweeping generalizations about the genetic architecture of the trait based
      on these results. A previous study fine mapped mate preference variation between
      one pair of Drosophila pseudoobscura lines and identified 2 strong-effect
      behavioral quantitative trait loci (QTLs). Here, we replicated the previous
      study's mapping design to examine the extent of variation at these behavioral
      QTLs across 6 pairs of lines, but we were unable to detect effects of either QTL
      region in the pairs of lines studied. We suggest that the low-discrimination
      alleles at these 2 QTLs may occur at low frequency within D. pseudoobscura,
      although other explanations for the inconsistency are possible. These results
      underscore the need to examine multiple strains across a species when describing
      the genetic variation underlying behavioral traits.

PMID- 18728092
TI  - Abstracts of the EHDN (European Huntington Disease Network) Annual Meeting,
      September 4-7, 2008. Lisbon, Portugal.

PMID- 18728084
TI  - The karyotype of Franciscana dolphin (Pontoporia blainvillei).
AB  - Despite the recent increase in studies on franciscana dolphin (Pontoporia
      blainvillei) molecular biology, there has been no published karyotype
      information, as opportunities for sampling live individuals are very rare. In the
      present study, the diploid number of the species was established from corneal
      cell cultures of 2 newborn male franciscanas live stranded (2n = 44). From the
      comparison of the chromosomal number to the cetacean karyotype phylogeny, we
      suggest that the most parsimonious hypothesis is that the ancestral character
      state in the group is the diploid number of 42, with an extra chromosome pair
      appearing independently twice during cetacean evolution, once in the suborder
      Odontoceti and once in the suborder Mysticeti. This information on chromosomal
      number may be useful to future genetic mapping projects of the species.

PMID- 18728093
TI  - Computer-based exercises for learning to read and spell by deaf children.
AB  - There is a surprising lack of systematic research evaluating the effects of
      reading exercises for young deaf children. Therefore, for this article, two
      computer-based exercises were developed and learning effects were determined by
      posttests. One (spelling oriented) exercise was to select the correct word among
      three orthographically similar alternatives that corresponds to a drawing or a
      sign (digital video). The other (meaning oriented) exercise was to select the
      correct sign or picture among three alternatives that corresponds to a written
      word. Eleven deaf Dutch children with a mean age of 7 years 10 months
      participated in the study. A first question was whether in single-word exercises
      the meaning or the spelling of a word should be emphasized. A second question was
      whether there was any effect of using drawings or signs to refer to the meaning
      of the word. The results reveal that emphasizing the word spelling is most
      effective for learning to read for deaf children and the findings also suggest
      that drawings are more efficient in the current exercises.

PMID- 18728094
TI  - Most intact human nervous systems know whether they are vertical or tilted, to
      around 4 degrees of accuracy between the perceived and real displacement.

PMID- 18728095
TI  - Ready for human spinal cord repair?

PMID- 18728096
TI  - Modelling the health benefits of smoking cessation in Japan.
AB  - BACKGROUND: In Japan, tobacco smoking is one of the main avoidable causes of
      disease and death. Although the benefits of smoking cessation for reducing
      disease risk and increasing longevity have been extensively documented, a
      relatively low proportion of Japanese smokers currently express a willingness to
      quit. This study attempted to quantify future reduction in the burden of smoking
      attributable disease that could result from increases in smoking cessation.
      METHODS: A simulation model was developed to project changes in mortality in
      Japan associated with increased quit attempts and use of nicotine replacement
      therapy (NRT) among smokers, incorporating data on smoking prevalence, cause
      specific mortality rates, quitting behaviour and NRT use and effectiveness.
      RESULTS: Approximately 46 000 lung cancer deaths and 56 000 cardiovascular
      disease deaths could be avoided over 20 years if the proportion of smokers making
      a quit attempt per year gradually increased to current US levels over 20 years.
      If each of these quit attempts were aided by NRT, the estimates of avoidable
      deaths would increase to 64 000 for lung cancer and 78 000 for cardiovascular
      disease. In this model, negligible deaths were avoided due to decreased smoking
      initiation over the 20-year simulation. CONCLUSION: Smoking cessation can have
      measurable short-term impacts on the smoking-related mortality burden in Japan.
      However, to achieve these gains, tobacco control policies should focus both on
      increasing smokers' willingness to quit and providing the support and therapies
      to increase the likelihood that smoking cessation attempts will succeed.

PMID- 18728097
TI  - Two-dimensional strain and atrial function: a study on patients after
      percutaneous closure of atrial septal defect.
AB  - AIMS: To assess the value of two-dimensional (2D) strain in assessing regional
      myocardial function along the atrial wall. METHODS AND RESULTS: We studied 20
      patients late after successful percutaneous atrial septal defect (ASD) closure.
      The analysis was performed for atrial longitudinal peak systolic strain on the
      interatrial septum, in correspondence of the device, and on the lateral wall of
      the left atrium. The speckle tracking indexes demonstrated almost the absence of
      any deformation on the Amplatzer ASD occluder, a bulky non-contractile element,
      passively moved by global heart motion. This study in a simple clinical model
      demonstrates that 2D strain is not influenced by global heart motion and
      tethering from adjacent segments and can also be used to study the regional
      atrial function. Moreover, both acquisition and post-processing times of 2D
      strain were very short, and the reproducibility was very good. CONCLUSION: All
      these above-mentioned characteristics make the 2D strain a tool fully compatible
      with the clinical scanning, able to provide additional clinical information.

PMID- 18728098
TI  - Role of real-time three-dimensional transoesophageal echocardiography for guiding
      transcatheter patent foramen ovale closure.
AB  - Patent foramen ovale (PFO) is a relatively common congenital condition which has
      been implicated in cryptogenic stroke as a result of paradoxical thromboembolism
      by right-to-left shunting. Many studies have demonstrated that transcatheter PFO
      closure significantly reduced the incidence of recurrent strokes in a small group
      of high-risk patients with PFO and atrial septal aneurysm compared with
      antithrombotic drugs. Two-dimensional transoesophageal echocardiography (2D TEE)
      has become the election technique for guiding patent foramen ovale closure. Real
      time Three-dimensional transoesophageal echocardiography (3D TEE) may be
      potentially superior to 2D TEE in the accurate assessment of the morphology and
      efficacy of transcatheter closure devices because of a better spacial
      orientation.

PMID- 18728099
TI  - Ovary and uterus transplantation.
AB  - Ovarian and uterine transplantation are procedures gaining more attention again
      because of potential applications in respectively fertility preservation for
      cancer and other patients and, more tentatively, women with uterine agenesis or
      hysterectomy. Cryopreservation of tissue slices, and possibly whole organs, is
      providing opportunities for banking ovaries for indefinite periods before
      transplanting them back to restore fertility. The natural plasticity of this
      organ facilitates grafting to different sites where they can be revascularized
      and rapidly restore the normal physiology of secretion and ovulation. Ischemic
      damage is a chief limitation because many follicles are lost, at least in
      avascular grafts, and functional longevity is reduced. Nevertheless, grafts of
      young ovarian tissue, even after cryopreservation, can be highly fertile in
      laboratory rodents and, in humans, autografts have functioned for up to 3 years
      before needing replacement. Transplantation by vascular anastomosis provides
      potentially longer function but it is technically much more demanding and riskier
      for the recipient. It is the only practicable method with the uterus, and has
      enabled successful pregnancies in several species, but not yet in humans.
      Contrary to claims made many years ago, neither organ is privileged
      immunologically, and allografts become rapidly rejected except in hosts whose
      immune system is deficient or suppressed pharmacologically. All in all,
      transplantation of these organs, especially the ovary, provides a broad platform
      of opportunities for research and new applications in reproductive medicine and
      conservation biology.

PMID- 18728101
TI  - Dependence of time to reach steady-state on the length of dosage interval.

PMID- 18728100
TI  - ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action
      potential propagation in nociceptors.
AB  - Voltage-gated sodium (Na(V)1) channels play a critical role in modulating the
      excitability of sensory neurons, and human genetic evidence points to Na(V)1.7 as
      an essential contributor to pain signaling. Human loss-of-function mutations in
      SCN9A, the gene encoding Na(V)1.7, cause channelopathy-associated indifference to
      pain (CIP), whereas gain-of-function mutations are associated with two inherited
      painful neuropathies. Although the human genetic data make Na(V)1.7 an attractive
      target for the development of analgesics, pharmacological proof-of-concept in
      experimental pain models requires Na(V)1.7-selective channel blockers. Here, we
      show that the tarantula venom peptide ProTx-II selectively interacts with
      Na(V)1.7 channels, inhibiting Na(V)1.7 with an IC(50) value of 0.3 nM, compared
      with IC(50) values of 30 to 150 nM for other heterologously expressed Na(V)1
      subtypes. This subtype selectivity was abolished by a point mutation in DIIS3. It
      is interesting that application of ProTx-II to desheathed cutaneous nerves
      completely blocked the C-fiber compound action potential at concentrations that
      had little effect on Abeta-fiber conduction. ProTx-II application had little
      effect on action potential propagation of the intact nerve, which may explain why
      ProTx-II was not efficacious in rodent models of acute and inflammatory pain.
      Mono-iodo-ProTx-II ((125)I-ProTx-II) binds with high affinity (K(d) = 0.3 nM) to
      recombinant hNa(V)1.7 channels. Binding of (125)I-ProTx-II is insensitive to the
      presence of other well characterized Na(V)1 channel modulators, suggesting that
      ProTx-II binds to a novel site, which may be more conducive to conferring subtype
      selectivity than the site occupied by traditional local anesthetics and
      anticonvulsants. Thus, the (125)I-ProTx-II binding assay, described here, offers
      a new tool in the search for novel Na(V)1.7-selective blockers.

PMID- 18728102
TI  - Assessing the reporting and scientific quality of meta-analyses of randomized
      controlled trials of treatments for anxiety disorders.
AB  - BACKGROUND: Meta-analyses of randomized controlled trials (RCTs) constitute the
      highest level of evidence, but their usefulness depends on their quality.
      OBJECTIVE: To assess the reporting and scientific quality of meta-analyses of
      RCTs on treatments for anxiety disorders. METHODS: Criteria for peer-reviewed,
      full-text retrieval included meta-analyses of RCTs of drugs versus active
      ingredient placebo, standard care, or psychotherapy. Sample populations were
      required to meet Diagnostic and Statistical Manual of Mental Disorders or
      International Classification of Diseases and Related Health Problems diagnostic
      criteria for anxiety disorders. Two reviewers independently searched EMBASE, EBM
      Reviews, Ovid MEDLINE, Ovid HealthSTAR, and International Pharmaceutical
      Abstracts from inception to August 2007. Search terms included meta-analysis,
      randomized controlled trials, anxiety, anxiolytic, anti
      depressant/antidepressant, and pharmacotherapy, without language restrictions.
      References and reviews were searched manually. Quality was assessed independently
      by 2 raters, using the Quality of Reporting of Meta-analyses (QUOROM) and the
      Overview Quality Assessment Questionnaire (OQAQ). The QUOROM was used to assess
      the reporting quality of the study, using an 18-item checklist, and the
      scientific quality was assessed with the OQAQ's 10-item checklist. Kendall's tau
      measured interrater reliability with statistical significance at p less than or
      equal to 0.01. Means and standard deviations described the overall quality. A
      time series analysis was performed. RESULTS: A total of 136 titles and abstracts
      were reviewed; 48 were retrieved, including 6 from the manual search. Thirty-two
      were excluded (not pooled analyses, inappropriate condition/treatment,
      duplications), leaving 16 studies published between 1995 and 2007. Agreement was
      high: tau = 0.801 (p < 0.01) for QUOROM and 0.834 (p < 0.01) for OQAQ. QUOROM
      quality scored 61% +/- 19%. Overall, the results sections of the studies scored
      lowest, while the introduction and discussion sections scored highest. The
      overall scientific quality was 58% +/- 28%. Most studies appropriately linked
      results to primary objectives but did not report how bias was avoided or how
      study validity was assessed. Quality increased nonsignificantly over time.
      CONCLUSIONS: Reporting/scientific quality was considered less than fair-to-good.
      Stakeholders should strive for higher scientific quality of meta-analyses.

PMID- 18728103
TI  - Pharmacokinetics and pharmacodynamics of intranasal versus intravenous fentanyl
      in patients with pain after oral surgery.
AB  - BACKGROUND: Fentanyl, a short-acting synthetic opioid, has a pharmacokinetic
      profile suited to fast relief of brief episodic pain. OBJECTIVE: To characterize
      the pharmacokinetic-pharmacodynamic correlation of intranasal and intravenous
      fentanyl in opioid-naive patients undergoing third molar extraction. METHODS: A
      double-blind, double-dummy, crossover design study was conducted, with patients
      randomized to receive 1 of 4 fentanyl doses (75, 100, 150, or 200 microg) by both
      the intravenous and intranasal routes. Venous fentanyl concentrations were
      determined for up to 180 minutes and pain scores were recorded up to 240 minutes
      postdose. Duration of effect and time to rescue medication were also recorded.
      RESULTS: The pharmacokinetics of intravenous fentanyl reflected a 2-compartment
      model with a clearance of approximately 1.5 L/min. There was moderate (<50%)
      between-subject variability (BSV; %CV [coefficient of variation]) in the systemic
      kinetics of fentanyl. Bioavailability of intranasal fentanyl was 89%, following
      first-order absorption, with a lag of approximately 5 minutes and a half-life of
      approximately 6.5 minutes. Interpatient absorption variability was approximately
      30% BSV for all absorption parameters. Intranasal versus intravenous
      administration led to a delayed mean fentanyl time to maximum concentration (13
      vs 6 min) and lower maximum concentration (1.2 vs 2.0 ng/mL). Analgesic effect
      lagged behind the venous fentanyl concentration, with a half-life of
      approximately 2.5 minutes as described by a fractional sigmoid maximum drug
      effect dynamic model. The concentration-analgesia relationship was steep, with a
      50% effective concentration of 0.46 ng/mL (Hill coefficient 3.5). Intranasal
      onset and offset of analgesia were slightly delayed, principally due to the delay
      and lag in systemic absorption, with slightly lower peak analgesic effect,
      compared with intravenous fentanyl. Duration of effect was directly related to
      intranasal fentanyl dose, with pain scores returning to predose values at
      approximately 120 minutes (75 microg) to approximately 240 minutes (200 microg)
      after a single dose. CONCLUSIONS: Intranasal fentanyl showed kinetic and dynamic
      properties that are desirable for the management of acute, episodic
      (breakthrough) pain.

PMID- 18728104
TI  - Sibutramine-associated QT interval prolongation and cardiac arrest.
AB  - OBJECTIVE: To report on a probable association between sibutramine and QT
      interval prolongation leading to ventricular fibrillation and cardiac arrest.
      CASE SUMMARY: A previously well 51-year-old woman with obesity but no other
      relevant past medical history or cardiac risk factors was prescribed sibutramine
      (initial dose 10 mg daily, increased to 15 mg daily after 10 wk). Four months
      after initiation of therapy, the woman developed ventricular fibrillation and was
      successfully resuscitated. On admission, an electrocardiogram (ECG) demonstrated
      sinus tachycardia without any ischemic changes and a prolonged QTc interval (545
      msec). A subsequent coronary angiogram revealed normal coronary arteries and no
      other abnormalities. Her QTc interval returned to normal (432 msec) by day 2 and
      remained within normal limits (<440 msec) thereafter. Due to a favorable
      neurologic recovery and the absence of any cardiac structural abnormality, the
      patient was readmitted for implantation of an automatic implantable cardioverter
      defibrillator on day 35 and remained well from a cardiac and neurologic
      standpoint at a 2-year follow-up examination. DISCUSSION: Sibutramine acts
      centrally to inhibit noradrenaline, dopamine, and serotonin reuptake, thereby
      sharing similar actions of other QT interval-prolonging drugs. Therefore,
      sibutramine might be anticipated to also share a tendency to QT interval
      prolongation. The current prescribing information for sibutramine does not
      specifically list any precautions or adverse reactions related to QT interval
      prolongation. QT interval prolongation associated with sibutramine in this case
      is considered probable based on the Naranjo probability scale. CONCLUSIONS:
      Clinicians prescribing sibutramine should monitor their patients for ECG
      abnormalities and be cautious in coprescribing drugs known to prolong the QT
      interval.

PMID- 18728105
TI  - Duloxetine-associated tachycardia.
AB  - OBJECTIVE: To report a case of symptomatic tachycardia that was successfully
      treated with propranolol in a patient receiving duloxetine. CASE SUMMARY: A 26
      year-old man presented with episodes of fatigue, tachycardia, diaphoresis, and
      chest pain approximately 2 months after the initiation of duloxetine 20 mg/day
      for dysthymic disorder. Cardiac workup including echocardiogram, exercise
      treadmill testing, and Holter monitoring was negative, except for tachycardia
      (heart rate 110-120 beats/min). Duloxetine was withheld, and the patient's heart
      rate returned to normal in less than a week. Duloxetine was restarted at the same
      dosage, and tachycardia returned within 2 days. Propranolol was added to the
      treatment regimen to lower the heart rate. Because of therapeutic failure of
      other antidepressants, duloxetine was continued because of its beneficial effects
      on mood. DISCUSSION: One published case report describing tachycardia in
      association with duloxetine in 2 heart failure patients was found in a MEDLINE
      search (1966-July 2008). Increased blood pressure and heart rate have been
      reported in duloxetine trials. The proposed mechanism for duloxetine-induced
      tachycardia is its effects on norepinephrine, which impact the cardiovascular
      system. Use of the Naranjo probability scale indicated duloxetine as a probable
      cause of this patient's tachycardia. CONCLUSIONS: Clinicians should be aware of
      the possibility of clinically significant tachycardia in patients receiving
      duloxetine, even in low doses.

PMID- 18728107
TI  - Welcoming the e-age: the e-age has finally caught up with our Journal.

PMID- 18728106
TI  - Potential aluminum exposure from parenteral nutrition in patients with acute
      kidney injury.
AB  - BACKGROUND: Patients' exposure to and potential toxicity from aluminum in
      parenteral nutrition (PN) formulations is an important concern of healthcare
      providers. OBJECTIVE: To determine the potential for aluminum toxicity caused by
      PN in hospitalized adults who have risk factors of both acute kidney injury and
      PN. METHODS: Adults who required PN and had a serum creatinine (SCr) level at
      least 1.5 times greater than the admission SCr on the first day of PN were
      studied in a retrospective fashion. Protein was administered based on whether
      hemodialysis was being used (0.6-1 g/kg/day without hemodialysis; 1.2-1.5
      g/kg/day with hemodialysis). Aluminum exposure was determined for each patient by
      multiplying the volume of each PN component by its concentration of aluminum.
      Unpaired t-tests, Fisher's exact test, and analysis of variance were used for
      statistical analysis. Data are presented as mean +/- SD. RESULTS: Thirty-six
      patients (aged 50.4 +/- 20.4 y; weight 90.2 +/- 32.8 kg) were studied. Initial
      serum urea nitrogen and SCr were 47 +/- 23 and 3.3 +/- 1.4 mg/dL, respectively.
      Twelve patients received hemodialysis. The mean aluminum exposure was 3.8 +/- 2
      microg/kg/day in the 36 patients. Of these, 29 had safe calculated aluminum
      exposure (<5 microg/kg/day) and 7 had high calculated aluminum exposure (>5
      microg/kg/day). Patients with safe aluminum exposure had significantly higher SCr
      levels than did those with high aluminum exposure (3.5 +/- 1.5 vs 2.2 +/- 0.7
      mg/dL; p < 0.04). Patients with high aluminum exposure received significantly
      more aluminum from calcium gluconate compared with those who had safe aluminum
      exposure (357 +/- 182 vs 250 +/- 56 microg/day; p < 0.02). Limitations of the
      study include its retrospective design, which resulted in calculated versus
      direct measurement of aluminum. CONCLUSIONS: Using our calculations, we believe
      that most patients with acute kidney injury who require PN do not receive
      excessive exposure to aluminum from the PN formulation, despite having 2 risk
      factors (acute kidney injury, PN) for aluminum toxicity.

PMID- 18728108
TI  - Evaluation of a health promotion intervention for skin cancer prevention in
      Spain: the SolSano program.
AB  - The incidence of skin cancer is increasing worldwide, and Spain is no exception.
      SolSano is the first Spanish health education program for sun safety directed at
      elementary school children. The objective was to evaluate SolSano's effects on
      students' knowledge, attitudes and practices about sun safety. A non-randomized,
      before/after, community intervention without control group, with schools as the
      unit of intervention, was used for the study. Five thousand eight hundred and
      forty-five children from 215 Aragonese Primary Schools (Grades 1-2) participated
      in the program in their classes during the 2004-2005 academic year. The
      educational package contained an activity guide for teachers, a workbook for each
      pupil, a poster and an informative pamphlet for families. The pre-test and post
      test surveys were similar and were composed of two parts: the first part uses the
      'Draw and Write research strategy' and the second part was a questionnaire. One
      thousand five hundred and twenty-two students completed both questionnaires,
      49.2% were boys, and the mean age was 6.6; 45.7% self-reported pale skin and easy
      sunburn and 48% dark skin and rarely sunburn; 72.3% of the children reported
      having dark hair and eyes, and 51.6% freckles or moles. The mean score for the
      complete survey significantly increased by 1.55 points (1.38-1.72) after the
      intervention (p < 0.001), and girls did better than boys. Sunscreens were the
      most-commonly employed sun protection strategy while strategies such as seeking
      shadow and wearing clothes exhibited the greatest increase after the SolSano
      program [percentage increase of 19.3% (16.4-22.3) and 26.8% (23.4-30.3),
      respectively]. At baseline, 35.8% of children reported sunburns during the
      previous summer compared with 23.5% after the program. SolSano also achieved a
      slight reduction in the percentage of students who desired to be tanned. Our
      study demonstrates that significant knowledge can be acquired, attitudes
      regarding the healthiness of a tan can be modified and intentions to change sun
      protection behaviour can be promoted by well-designed educational programs.

PMID- 18728109
TI  - Health-promoting school development in Zhejiang Province, China.
AB  - In 2003, after three pilot projects successfully implemented WHO's Health
      Promoting Schools (HPS) concept, officials in Zhejiang Province, China, expanded
      to additional 51 schools (93,000 students and their families and 6800 school
      personnel). Each school identified a health issue to begin HPS development,
      followed by conceptual orientation, resource mobilization, teacher training,
      surveys, interventions, outreach and evaluation. This study focused on the extent
      to which participating schools implemented the HPS concept and improved their
      psycho-social environments (PSEs). Forty-nine of the 51 schools met China's HPS
      criteria. Schools with fewer resources and with substantial resources, i.e.
      schools in both rural and urban areas, met the criteria. Schools' PSEs, as
      measured by the PSE Profile, improved as they became HPS. Findings from
      interviews and observations identified strong encouragement and support from
      officials, school personnel, students, parents and community leaders, and
      consistency of HPS with the national policy on quality education, as success
      factors.

PMID- 18728110
TI  - Challenges in assessing the implementation and effectiveness of physical activity
      and nutrition policy interventions as natural experiments.
AB  - The Ontario (Canada) government has instituted a policy requiring elementary
      schools to offer at least 20 min of daily physical activity for students in
      Grades 1-8 and replace non-nutritious vending machine foods with healthier
      choices. These policy interventions represent 'natural experiments' offering
      unique opportunities for conducting research and evaluation. The use of natural
      experiments to contribute evidence on the effectiveness of policy interventions
      is identified as an underused tool for public health [Tudor-Locke, C., Ainsworth,
      B. E. and Popkin, B. M. (2001) Active commuting to school: an overlooked source
      of children's physical activity? Sports Medicine, 31, 309-313; Petticrew, M.,
      Cummins, S., Ferrell, C., Findlay, A., Higgins, C., Hoy, C. et al. (2005) Natural
      experiments: an underused tool for public health? Public Health, 119, 751-757].
      To date, some Canadian school-based food and nutrition policies are being
      monitored, but their impact on child and youth obesity is unknown [Canadian
      Institute for Health Information. (2006) Improving the Health of Canadians:
      Promoting Healthy Weights, Ottawa, ON]. There are a number of challenges to the
      evaluation of policy interventions as natural experiments. Often, there are
      little or no baseline data available to use as the basis for assessing change.
      Government policies that result in the adoption of particular approaches across
      large jurisdictions, such as provinces, may result in wide variation in the
      design and implementation of interventions. Thus, in some cases, natural
      experiments may be at risk of having low potential to be adequately evaluated on
      key outcomes. In this paper, we discuss the context of these challenges in
      relation to the Ontario government school physical activity and nutrition
      policies.

PMID- 18728111
TI  - The detection and monitoring of comprehension errors by preschool children with
      and without language impairment.
AB  - PURPOSE: In this study, the authors examined emerging comprehension monitoring,
      including error detection, evaluation, and correction within the context of story
      understanding in preschool children with and without language impairment. METHOD:
      Thirty-seven children between the ages of 30 and 61 months completed an online
      comprehension monitoring task. There were 3 groups: 10 children with language
      impairment, 13 typically developing children who were matched for age, and 14
      typically developing children who were matched for receptive vocabulary. RESULTS:
      Analyses of variance revealed that children with language impairment attained
      significantly lower scores on the comprehension monitoring task than both age
      matched and language-matched groups. CONCLUSION: The skills underlying successful
      comprehension monitoring that may be affected in young children with language
      impairment are discussed.

PMID- 18728112
TI  - Toward validation of a minimal competence phonetic core for african american
      children.
AB  - PURPOSE: This study aimed to show (a) whether the minimal competence core (MCC)
      of consonants used by African American preschoolers in I. Stockman (2006) can be
      observed in a larger group of children using shorter and more controlled speech
      samples and (b) whether the MCC pass/fail outcomes are differentially related to
      performance on selected criterion measures of typical and atypical speech.
      METHOD: Word-initial single and clustered consonants were sampled in the
      conversational speech of 120 Head Start students who were distributed in a
      northern (Lansing, Michigan) and a southern (Baton Rouge, Louisiana) regional
      location. RESULTS: The data generally corroborated the earlier preliminary
      report, which was based on just 7 children. More than 80% of the children met
      criteria for passing the core set of phonetic competencies, which included word
      initial consonant clusters and 13 consonant singletons. Pass/fail outcomes were
      significantly related to suspected clinical delay and the overall Percentage of
      Consonants Correct-Revised (PCC-R). CONCLUSION: The initial consonant core
      identified in this study is potentially useful for identifying speech delay among
      young African American children. Clinical and research issues related to its use
      for diagnostic screening are discussed.

PMID- 18728113
TI  - Effects of onset- and rhyme-related distractors on phonological processing in
      children with specific language impairment.
AB  - PURPOSE: This study used the cross-modal picture-word interference task of P. J.
      Brooks and B. MacWhinney (2000) to compare effects of phonologically related
      words on lexical access in children with specific language impairment (SLI).
      METHOD: Children (7;1 [years;months]-11;2) named pictures while ignoring auditory
      distractors. Three stimulus asynchrony conditions varied the timing of
      distractors relative to the pictures. Experiment 1 presented onset-related (bell
      bed), unrelated (clown-bed), neutral (go-bed), and identical (bed-bed)
      distractors. Experiment 2 presented rhyme-related instead of onset-related
      distractors (clock-sock). RESULTS: Children with SLI produced longer reaction
      times (RTs) and more errors than their typical language development (TLD) peers.
      For children with SLI, onset-related distractors led to slower RTs than unrelated
      distractors (inhibition) when presented before the picture, and faster RTs
      (facilitation) when presented after the picture. Children with TLD showed
      facilitation from onset-related distractors when presented after the picture but
      no inhibition when presented before the picture. Both groups failed to show
      facilitation from rhyme-related distractors. CONCLUSIONS: The priming effects
      from onset-related distractors and lack of effects from rhyme-related distractors
      in SLI supports "just-in-time" incremental processing, similar to children with
      TLD. However, children with SLI experience phonological interference from members
      of a lexical cohort while accessing words. Results are discussed with respect to
      observed word finding and word learning difficulties in SLI.

PMID- 18728114
TI  - Submental sEMG and hyoid movement during Mendelsohn maneuver, effortful swallow,
      and expiratory muscle strength training.
AB  - PURPOSE: This study investigated the concurrent biomechanical and
      electromyographic properties of 2 swallow-specific tasks (effortful swallow and
      Mendelsohn maneuver) and 1 swallow-nonspecific (expiratory muscle strength
      training [EMST]) swallow therapy task in order to examine the differential
      effects of each on hyoid motion and associated submental activation in healthy
      adults, with the overall goal of characterizing task-specific and overload
      properties of each task. METHOD: Twenty-five healthy male and female adults (M =
      25 years of age) participated in this prospective, experimental study with 1
      participant group. Each participant completed all study tasks (including normal
      swallow, Mendelsohn maneuver swallow, effortful swallow, and EMST task) in random
      order during concurrent videofluoroscopy and surface electromyography recording.
      RESULTS: Results revealed significant differences in the trajectory of hyoid
      motion as measured by overall displacement and angle of elevation of the hyoid
      bone. As well, timing of hyoid movement and amplitude differences existed between
      tasks with regard to the activation of the submental musculature. CONCLUSIONS:
      Study results demonstrated differential effects of the 3 experimental tasks on
      the principles of task specificity and overload. These principles are important
      in the development of effective rehabilitative programs. Subsequent direction for
      future research is suggested.

PMID- 18728115
TI  - Effects of feedback frequency and timing on acquisition, retention, and transfer
      of speech skills in acquired apraxia of speech.
AB  - PURPOSE: Two studies examined speech skill learning in persons with apraxia of
      speech (AOS). Motor-learning research shows that delaying or reducing the
      frequency of feedback promotes retention and transfer of skills. By contrast,
      immediate or frequent feedback promotes temporary performance enhancement but
      interferes with retention and transfer. These principles were tested in the
      context of a common treatment for AOS. METHOD: Two studies (N = 4, N = 2)
      employed single-subject treatment designs to examine acquisition and retention of
      speech skills in adults with AOS under different feedback conditions. RESULTS:
      Reduced-frequency or delayed feedback enhanced learning in 3 participants with
      AOS. Feedback manipulation was not an influential variable in 3 other cases in
      which stimulus-complexity effects may have masked treatment effects. CONCLUSIONS:
      These findings demonstrate that individuals with AOS can benefit from structured
      intervention. They provide qualified support for reduction and delay of feedback,
      although interaction with other factors such as stimulus complexity or task
      difficulty needs further exploration. This study adds to the growing body of
      literature investigating the use of principles of motor learning in treating AOS
      and provides impetus for consideration of pre-treatment variables that affect
      outcome in treatment studies.

PMID- 18728116
TI  - How should oncologists face complementary and alternative medicine?

PMID- 18728117
TI  - A case of chondrosarcoma of the nasal septum.

PMID- 18728118
TI  - Comparison of time trends in testicular cancer incidence (1973-97) in East Asia,
      Europe and USA, from Cancer Incidence in Five Continents Vols IV-VIII.

PMID- 18728119
TI  - Health literacy and health actions: a review and a framework from health
      psychology.
AB  - The association between performance on health literacy measures and health
      outcomes is well established. The next step is to understand the processes
      through which health literacy affects health. This review introduces a framework
      drawing on ideas from health psychology and proposing that associations between
      health literacy and health outcomes could be mediated by a range of health
      actions involving access and use of health care, patient-provider interactions,
      and the management of health and illness. The framework outlines routes through
      which health literacy might affect either health actions themselves or the
      motivational and volitional determinants that have been identified in social
      cognition models. The implications of the framework for future research and
      intervention strategies are discussed.

PMID- 18728120
TI  - Thyroid nodules: a review of current guidelines, practices, and prospects.
AB  - In 2006, two major society-sponsored guidelines and one major consensus statement
      for thyroid diagnosis and management were published by: the American Association
      of Clinical Endocrinologists/Associazione Medici Endocrinologi (AACE/AME); the
      American Thyroid Association (ATA); and the European Thyroid Association (ETA). A
      careful review of these guidelines reveals that despite many similarities,
      significant differences are also present, likely reflecting differences in
      practice patterns, interpretation of existing data, and availability of resources
      in different regions. The methodology of the guidelines is similar, but a few
      differences in the rating scale make a rapid comparison of the strength of both
      evidence and recommendations difficult for the use in current clinical practice.
      Some recommendations are based mostly on experts' opinion. Thus, a same
      recommendation may be based on a different evidence; on the other hand, sometimes
      the same evidence may induce a different recommendation. Therefore, efforts are
      needed to produce a few high-quality clinical studies to close the evidence gaps
      in the still controversial fields of thyroid disease and to create a joint task
      force of the most authoritative societies in the field of thyroid disease in
      order to reach a common document for clinical practice recommendations.

PMID- 18728121
TI  - Undescended testes: a consensus on management.
AB  - The mode of treatment best for undescended testes is controversial, and local
      traditions often override knowledge gained from randomized controlled studies. In
      order to reach a consensus within the Nordic countries on the current state-of
      the-art of treatment, a group of specialists in testicular physiology, paediatric
      surgery/urology, endocrinology, andrology, pathology and anaesthesiology from all
      the Nordic countries met for 2 days. Before the meeting, reviews of the
      literature had been prepared by the participants. Judging from published meta
      analyses, hormonal treatment has low efficacy. Although 15-20% of retained testes
      descend during hormonal treatment, one-fifth of these re-ascend later on. Also,
      treatment with human chorionic gonadotropin (hCG) may be harmful to future
      spermatogenesis through increased apoptosis of germ cells. Orchiopexy, on the
      contrary, results in about 95% anatomical success, with a low (about 1%) risk of
      complications. The optimal time for orchiopexy has also been debated. However, a
      recent randomized controlled study shows that surgery at 9 months of age is
      followed by a better post-operative growth of the testes than surgery at 3 years,
      which supports previous arguments for early surgery. The unanimous conclusion of
      the group was that surgery is generally the preferred mode of treatment, rather
      than hCG or GnRH treatments. Orchiopexy should be performed between 6 and 12
      months of age, or soon after diagnosis, if that occurs later. If a testis is
      found to be undescended at any age after 6 months, the patient should be referred
      for surgery. Referral should be to paediatric rather than general
      surgeons/urologists if the boy is less than 1 year old, if he has bilateral or
      non-palpable testes, or if he has got relapse of cryptorchidism.

PMID- 18728122
TI  - Polymorphisms in the adiponutrin gene are associated with increased insulin
      secretion and obesity.
AB  - OBJECTIVE: The insulin responsive adiponutrin or patatin-like phospholipase 3
      (PNPLA3, previously ADPN) gene shows association with obesity and in vitro
      adipocyte lipolysis. This study aimed to replicate the association between PNPLA3
      variants and obesity, and to investigate their effect on insulin resistance and
      beta-cell function. METHODS: rs738409 (Met148Ile) and rs2072907 (C to G) were
      genotyped using TaqMan allelic discrimination assay in a Swedish population-based
      sample (n=1811). Oral glucose tolerance test (OGTT) with data from three time
      points (0, 30, and 120 min) were available from individuals under the age of 50
      years (n=973). RESULTS: Both variant alleles were associated with decreased
      prevalence of obesity (P<0.05); odds ratio 0.75 (0.61-0.93) per carried Ile
      allele for rs738409 and 0.80 (0.64-1.00) per carried G-allele for rs2072907. For
      obesity as a quantitative trait, there was no association in the whole
      population, but in obese subjects body mass index (BMI; P=0.023) and waist
      (P=0.0098) were higher in carriers of the Ile-allele. The Ile-carriers also
      displayed decreased insulin secretion in response to OGTT (30 min insulin;
      P=0.007, insulinogenic index; P=0.0051) with no significant differences in
      fasting plasma glucose (P=0.31), beta-cell function (disposition index; P=0.17)
      or homeostasis model of assessment insulin resistance (HOMA-IR; P=0.063). The
      correlation between BMI and HOMA-IR differed (Met/X versus Ile/Ile, P=0.028), Met
      allele carriers were seemingly more insulin resistant at a lower BMI. The
      rs2072907 variant shows similar results for insulin secretion. The significance
      of this finding remained after adjusting for age, gender, and level of self
      reported leisure-time physical activity. CONCLUSION: We confirm the association
      between PNPLA3 and obesity. In addition, the rs738409 variant was associated with
      insulin secretion. There seems to be a differential effect of the Ile-allele
      depending on the degree of obesity, possibly as a consequence of insulin
      resistance.

PMID- 18728123
TI  - Methylenetetrahydrofolate reductase C677T polymorphism is associated with central
      adiposity and increased androgenicity in healthy postmenopausal women.
AB  - OBJECTIVE: To assess the association of genetic polymorphisms related to
      cardiovascular disease (CVD) risk with anthropometric parameters and indices of
      androgenicity in healthy postmenopausal women. DESIGN: Cross-sectional study in a
      University Menopause Clinic. METHODS: The following polymorphisms were assessed
      in 84 healthy postmenopausal women: glycoprotein IIIa Leu33Pro, apolipoprotein
      E2/E3/E4, methylenetetrahydrofolate reductase (MTHFR) Ala222Val, apolipoprotein B
      Arg3500Gln, paraoxonase 1 Gln192Arg, plasminogen activator inhibitor 1 4G/5G,
      cholesterol-7 alpha-hydroxylase A-204C, and cholesterol ester transfer protein
      (TaqIB) B1/B2. Hormonal assays included FSH, LH, 17-beta-estradiol, testosterone,
      sex hormone-binding globulin (SHBG), DHEA sulfate, Delta-4-androstenedione
      (Delta4A), free androgen index (FAI), free estrogen index (FEI), and homocysteine
      (Hcy). The anthropometric components were body mass index (BMI) and waist-to-hip
      ratio (WHR). RESULTS: MTHFR Ala222Val polymorphism was positively associated with
      testosterone, FAI, and FEI (P=0.001, P=0.0004, and P=0.014 respectively) and
      negatively with SHBG (P=0.047). Furthermore, women bearing this polymorphism had
      higher BMI and WHR compared with women with the wild-type variant (P=0.027 and
      P=0.044 respectively). CONCLUSIONS: MTHFR Ala222Val polymorphism is associated
      with increased androgenicity and elevated BMI and WHR in healthy postmenopausal
      women. The significance of this association with respect to the CVD risk of
      postmenopausal women remains to be elucidated in future studies.

PMID- 18728124
TI  - Monogenic polycystic ovary syndrome due to a mutation in the lamin A/C gene is
      sensitive to thiazolidinediones but not to metformin.
AB  - CONTEXT: Despite the very high prevalence of the polycystic ovary syndrome
      (PCOS), the underlying pathogenetic mechanism has remained obscure. OBJECTIVE: To
      determine the cause of two sisters' PCOS associated with severe insulin
      resistance. DESIGN: Clinical case report. Methods Two sisters who presented with
      hyperandrogenism and menstrual disorders in the context of PCOS, and were
      subsequently found to be severely insulin resistant. Physical examination
      revealed muscular hypertrophy with a paucity of fat in the extremities, trunk and
      gluteal regions, in spite of excess fat deposits in the face, neck and
      dorsocervical region. Known genes involved in familial partial lipodystrophy were
      screened. At the same time, metformin (1700 mg/day) was commenced. After 2-3
      years of uninterrupted therapy, lack of clinical improvement led to the
      introduction of pioglitazone (30 mg/day). RESULTS: Both sisters were found to be
      heterozygous for the R482Q mutation in the lamin A/C gene (LMNA) gene,
      establishing the definitive diagnosis as Dunnigan-type familial partial
      lipodystrophy complicated by severe insulin resistance and secondary PCOS.
      Treatment with pioglitazone resulted in progressive amelioration of insulin
      resistance, hyperinsulinaemia and hyperandrogenaemia. Menses also improved, with
      restoration of a eumenorrhoeic pattern, and the framework of ultrasound PCO was
      in complete remission. CONCLUSIONS: Assessment of insulin sensitivity and adipose
      tissue topography should be a key part of the initial evaluation of patients with
      PCOS. Identifying such forms of PCOS with monogenic insulin resistance as the
      primary pathogenic abnormality may have practical implications for therapy, since
      they respond to thiazolidinediones, but not to metformin.

PMID- 18728125
TI  - Signal regulatory protein alpha1 is involved in the inhibitory effect of
      glucocorticoid receptor on the proliferation of murine macrophage RAW264.7 cell
      and mouse peritoneal macrophage.
AB  - Glucocorticoid (GC) effectively suppresses immune and inflammatory responses and
      inhibits the growth of several types of cells, but the role of GC and its
      receptor on macrophage proliferation is unclear. In our previous work, we found
      RAW-GR(-) cells (murine macrophage RAW264.7 cells stably transfected with GR
      siRNA expression vector by RNA interference) grew faster by about twofold. In
      this study, we further explored the role and mechanisms of GC/GR on the
      proliferation of macrophage. We found that the growth of RAW264.7 cells was
      inhibited by dexamethasone (Dex) in a concentration-dependent manner. The mRNA
      and protein levels of signal regulatory protein alpha1 (SIRPA) were induced by
      GC/GR in RAW264.7 cells and SIRPA expression was decreased remarkably in RAW-GR(
      ) cells. Overexpression of SIRPA negatively regulated the proliferation of RAW
      GR(-) cells, and inhibition of SIRPA expression by a small from RNA interference
      attenuated Dex-induced proliferation inhibition in RAW264.7 cells. The
      proliferation inhibition of GC/GR was also found in mouse peritoneal macrophage,
      which was associated with the increase in SIRPA induced by GC/GR as well. In
      addition, elevation of the expression of CDK2, cyclinD1, and cyclinB1, but not
      phosphorylated ERK1/2 and p38, was found in RAW-GR(-) cells. In conclusion, we
      provided the novel evidences that GC/GR inhibited the growth of RAW264.7 cells
      and mouse peritoneal macrophage, and the antiproliferative effect of GC/GR on
      these cells was at least in part a result from GC/GR-induced SIRPA expression. Up
      regulation of CDK2, cyclinD1, and cyclinB1 was also related to the increased
      proliferation of RAW-GR(-) cells.

PMID- 18728127
TI  - Two cytochrome P450 aromatase genes in the hermaphrodite ricefield eel Monopterus
      albus: mRNA expression during ovarian development and sex change.
AB  - Previously, the ricefield eel (Monopterus albus) was speculated to have only one
      cytochrome p450 aromatase gene. In this study, however, the cDNAs encoding two
      distinct cytochrome p450 aromatases, cyp19a1a and cyp19a1b, were isolated. The
      genomic organizations of both cyp19 genes were conserved when compared with other
      teleosts. Northern blot detected an abundant expression of cyp19a1a in the ovary,
      and cyp19a1b in the hypothalamus. RT-PCR coupled with Southern blot showed that
      cyp19a1a was expressed predominantly in the gonads of both sexes, with higher
      levels in the ovary than testis, while cyp19a1b was expressed in all the tissues
      examined in the male, but only in the brain and pituitary in the female. The
      levels of cyp19a1a mRNA in the ovary were increased significantly during
      vitellogenesis, but decreased significantly at mature stage. The levels of
      cyp19a1b mRNA in the brain and pituitary did not vary significantly during
      vitellogenesis. As ovarian development shifted from vitellogenesis to maturation,
      the levels of cyp19a1b mRNA was decreased significantly in the brain, but
      increased significantly in the pituitary. During natural sex change from female
      to male, the levels of cyp19a1a mRNA in the gonad were significantly decreased.
      The levels of cyp19a1b mRNA in the hypothalamus were significantly increased at
      the early intersexual phase, whereas the expression levels in the pituitary were
      significantly decreased at the intersexual phases. Taken together, these results
      showed a novel sexual dimorphism of cyp19a1b mRNA tissue distribution, and both
      CYP19 genes were associated with the ovarian development and natural sex change
      of the ricefield eel.

PMID- 18728128
TI  - Public perception of sex offender social policies and the impact on sex
      offenders.
AB  - This study examines the public perception of sex offender policies and the
      perceived impact of sex offender policies on the sex offenders themselves.
      Specifically, this study explores how the community feels about the effectiveness
      of policies such as registration and community notification (Megan's Law), and
      housing restrictions in reducing sexual recidivism. Data are collected from 115
      participants from a nationwide online community message board. Results suggest
      that although most individuals support Megan's Law, they do not feel the policy
      reduces recidivism. Furthermore, the majority of the participants also do not
      believe that housing restriction statutes are effective in reducing sexual
      recidivism. When questioned about the policy impact on sex offenders, the
      majority of respondents agree that as a consequence of Megan's Law, sex offenders
      are afraid for their safety; however, they do not believe that residence
      restrictions hinder sex offenders' employment opportunities. Findings from this
      study are discussed as they pertain to public policy and sex offender
      reintegration.

PMID- 18728129
TI  - Media consideration of sex offenders: how community response shapes a gendered
      perspective.

PMID- 18728130
TI  - Effects of stretching and heat treatment on hamstring extensibility in children
      with severe mental retardation and hypertonia.
AB  - OBJECTIVES: To examine the effect of heat and duration of stretching on the
      extensibility of hamstring muscles and their electromyographic responses to
      passive stretch in children with hypertonia and severe mental retardation.
      DESIGN: Randomized cross-over trial. SETTING: Developmental disability unit in a
      local hospital. PARTICIPANTS: Twenty-nine subjects (9 females) with ages ranged
      from 4 to 13 years with spastic and/or dystonic hypertonia and hamstring
      tightness. INTERVENTIONS: Subjects received four treatment sessions in random
      order with each consisting of five repetitions of stretching: (A) 10-second
      stretching, (B) 30-second stretching, (C) hot pack followed by 10-second
      stretching, and (D) hot pack followed by 30-second stretching. Each treatment
      session comprised five repetitions of stretch and successive treatments were
      separated by at least 24 hours. MAIN OUTCOME MEASURES: The distance between
      greater trochanter and lateral malleolus and hamstring electromyographic (EMG)
      activity during passive knee extension stretching. RESULTS: Two-way ANOVA showed
      a larger increase in hamstring extensibility in conditions C and D (1.3 +/- 1.1
      cm) than conditions A and B (0.7 +/- 0.9 cm) (P<0.001). For the EMG recordings,
      conditions B and D (-25.1 +/- 58.4 microV) had greater decrease than conditions A
      and C (-3.5 +/- 36.6 microV) (P= 0.039). CONCLUSIONS: Heat application to the
      hamstrings before stretching could result in greater increase in extensibility
      than stretching alone in children with hypertonia and severe mental retardation.
      Stretching could promote relaxation of the hamstring muscles regardless of prior
      heat treatment. Stretching sustained for 30 seconds led to greater relaxation
      than that for 10 seconds.

PMID- 18728126
TI  - The role of thyroid hormone in testicular development and function.
AB  - Thyroid hormone is a critical regulator of growth, development, and metabolism in
      virtually all tissues, and altered thyroid status affects many organs and
      systems. Although for many years testis has been regarded as a thyroid hormone
      unresponsive organ, it is now evident that thyroid hormone plays an important
      role in testicular development and function. A considerable amount of data show
      that thyroid hormone influences steroidogenesis as well as spermatogenesis. The
      involvement of tri-iodothyronine (T(3)) in the control of Sertoli cell
      proliferation and functional maturation is widely accepted, as well as its role
      in postnatal Leydig cell differentiation and steroidogenesis. The presence of
      thyroid hormone receptors in testicular cells throughout development and in
      adulthood implies that T(3) may act directly on these cells to bring about its
      effects. Several recent studies have employed different methodologies and
      techniques in an attempt to understand the mechanisms underlying thyroid hormone
      effects on testicular cells. The current review aims at presenting an updated
      picture of the recent advances made regarding the role of thyroid hormones in
      male gonadal function.

PMID- 18728131
TI  - Comparison of two extracorporeal shock wave therapy techniques for the treatment
      of painful subcalcaneal spur. A randomized controlled study.
AB  - OBJECTIVE: To describe and compare two extracorporeal shock wave therapy
      techniques for the treatment of painful subcalcaneal spur. DESIGN: Random
      assignment to two groups of treatment with two and eight months follow-up.
      SETTING: The data were collected in outpatients. SUBJECTS: Forty-five subjects
      with a history of at least six months of heel pain were studied. INTERVENTIONS:
      Each subject received a three-session ultrasound-guided extracorporeal shock wave
      therapy (performed weekly). Perpendicular technique was used in group A (n=22,
      mean age 59.3 +/- 12 years) and tangential technique was used in group B (n= 23,
      mean age 58.8 +/- 12.3 years). MAIN OUTCOME MEASURES: Mayo Clinical Scoring
      System was used to evaluate each subject before the treatment and at two and
      eight months follow-up. RESULTS: Mayo Clinical Scoring System pretreatment scores
      were homogeneous between the groups (group A 55.2 +/-18.7; group B 53.5 +/- 20;
      P>0.05). In both groups there was a significant (P<0.05) increase in the Mayo
      Clinical Scoring System score at two months (group A 83.9 +/- 13.7; group B 80 +/
      15,8) and eight months (group A 90 +/- 10.5; group B 90.2 +/-8.7) follow-up. No
      significant differences were obtained comparing the Mayo Clinical Scoring System
      scores of the two groups at two and eight months follow-up. CONCLUSIONS: There
      was no difference between the two techniques of using extracorporeal shock wave
      therapy. The tangential technique was found to be better tolerated as regards
      treatment-induced pain, allowing higher energy dosages to be used.

PMID- 18728132
TI  - Validity and responsiveness of the Rehabilitation Activities Profile (RAP) in
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the internal consistency, validity and responsiveness
      of the Rehabilitation Activities Profile (RAP; a rehabilitation tool structuring
      the multidisciplinary team care process) in patients with rheumatoid arthritis.
      METHODS: In 85 rheumatoid arthritis patients admitted to a rheumatology clinic
      the RAP was applied at admission, at discharge, and six weeks thereafter.
      Additional assessments included measures of physical and psychological
      functioning, disease activity and quality of life. The internal consistency of
      the RAP was determined with Cronbach's alpha. Associations between the RAP and
      other outcome measures were determined by Spearman rank correlation coefficients.
      Responsiveness measures included the standardized response mean (SRM), effect
      size (ES) and responsiveness ratio (RR). RESULTS: Cronbach's alpha of the RAP
      total score was 0.78. The RAP total score correlated significantly with all other
      outcome measures. The mean RAP total score improved from 15.2 to 13.2 at
      discharge (change -2.0; 95% confidence interval (CI) -3.4 to -0.7) and to 11.5
      (change -3.7; 95% CI -3.9 to -1.5) six weeks thereafter. The responsiveness of
      the RAP total score was low (standardized response mean -0.34, effect size -0.30)
      to high (responsiveness ratio -0.87) at discharge and moderate (standardized
      response mean -0.54, effect size -0.55) to high (responsiveness ratio -1.56) six
      weeks thereafter. CONCLUSIONS: The RAP appeared to be an internally consistent,
      valid and responsive measure to reflect limitations on the level of activities
      and participation in patients with rheumatoid arthritis admitted for
      multidisciplinary team care.

PMID- 18728133
TI  - A life-breaking event: early experiences of the consequences of a hip fracture
      for elderly people.
AB  - OBJECTIVE: To explore and describe the consequences of an acute hip fracture as
      experienced by home-dwelling elderly people shortly after discharge from
      hospital. DESIGN: Semi-structured interviews using the phenomenographic method.
      SUBJECTS AND SETTING: Eighteen subjects were interviewed in their own homes one
      month after discharge. RESULTS: The interviewees described experiences of changes
      in their relation to the body, themselves, to others and to their whole life
      situation. These experiences were described as being limited in movement, having
      lost confidence in the body, becoming humble and grateful, respecting oneself and
      one's own needs, becoming more dependent on others, gaining more human contact
      and being treated in a friendly way by others, being secluded and trapped at
      home, feeling old, closer to death and having lost their zest for life, and
      taking one day at a time and being uncertain about the future. CONCLUSION:
      Experienced consequences of a hip fracture were multidimensional and involved
      dramatic changes in the interviewees' life situation, including existential
      thoughts and reappraisal of the years of life that remained. The results indicate
      that the fracture seemed not only to break the bone but also to cause social and
      existential cracks, as experienced in the early phase after the injury.

PMID- 18728134
TI  - Toll motorway accessibility for wheelchair users: a survey.
AB  - OBJECTIVE: To identify difficulties encountered by wheelchair users who travel on
      toll motorways, with the goal of defining areas for improvement. DESIGN: Survey.
      After observing a wheelchair user travelling on a toll motorway and using the
      associated services, we designed a self-questionnaire on perceptions by
      wheelchair users of toll motorway accessibility. SETTING: Toll motorway and
      rehabilitation hospital in France. SUBJECTS: We recruited 167 wheelchair users by
      advertisement and, to assess selection bias, 19 consecutive outpatients who
      visited our hospital's wheelchair showroom. INTERVENTION: None. RESULTS: Of the
      186 included subjects, 91 (49%) were used to driving independently on toll
      motorways. Among them, only 16% used automatic toll booths and 32% reported
      difficulties at toll booths. Furthermore, 53% routinely asked for help at filling
      stations, and only 27% were aware of the availability of a free-of-charge
      assistance service for disabled people at some filling stations. Among the 186
      toll motorway users, only 84 (45%) reported never encountering difficulties in
      lay-bys; 162 (87%) felt that toilet accessibility was the most important feature
      of lay-bys and 143 (77%) preferred the locked toilets reserved for disabled
      people. CONCLUSION: Wheelchair users reported difficulties on toll motorways that
      could be corrected fairly easily.

PMID- 18728135
TI  - Staying connected: re-establishing social relationships following vision loss.
AB  - OBJECTIVE: To examine the nature of relationship-related challenges experienced
      by adults with vision impairment, as well as the strategies employed to deal with
      them. DESIGN: Cross-sectional qualitative study. SETTING: Vision rehabilitation
      agency. SUBJECTS: Fifty-eight young, middle-aged and older adults with vision
      impairment. METHOD: Telephone and in-person interviews included an open-ended
      question about how having a vision impairment has changed relationships.
      Interviews were coded using a qualitative analytical approach. RESULTS:
      Participants' responses fell into two categories: difficulty in social situations
      was due either to other people's lack of understanding and/or one's own lack of
      visual cues. Responses were either to readjust one's behaviour to maintain
      relationships or to let relationships go or turn sour. Within these two
      directions, participants reported specific strategies. For readjusting one's
      behaviour, participants mentioned explaining themselves more and being more
      assertive, relying on other senses for information, 'faking' it through
      interactions, and being more selective about who they interacted with. For
      letting relationships go, participants reported either withdrawing and making
      fewer initiatives to socialize, or getting angry and telling people off.
      CONCLUSIONS: Study findings suggest that re-establishing relationships following
      vision loss is a multifaceted experience in which individuals employ different
      strategies. These need to be further researched, given their importance to
      individuals dealing with vision impairment.

PMID- 18728136
TI  - 'We're just sick people, nothing else': ... factors contributing to elderly
      stroke patients' satisfaction with rehabilitation.
AB  - OBJECTIVE: To identify factors contributing to elderly stroke patients'
      satisfaction with rehabilitation following stroke. DESIGN: Qualitative study
      using semi-structured interviews. SETTING: Interviews conducted in two phases,
      once in a stroke rehabilitation unit and once after hospital discharge. SUBJECTS:
      Twelve elderly stroke patients (seven women and five men, aged 60-87 years).
      RESULTS: One main category: 'To be treated with respect and dignity' was
      identified as a core factor contributing to patients' satisfaction with the
      rehabilitation services. This main factor was divided into five subcategories:
      (1) Being treated with humanity, (2) Being acknowledged as individuals, (3)
      Having their autonomy respected, (4) Having confidence and trust in
      professionals, (5) Dialogue and exchange of information. The statements covered a
      continuum from satisfaction via indifference to dissatisfaction. Expressions of
      satisfaction emerged mainly as general statements while expressions of
      dissatisfaction described situations in greater detail. Satisfaction was merely
      connected to daily care experiences and fulfillment of basic needs. Trust in
      providers and being dignified seemed more closely associated with satisfaction
      than being involved in treatment decisions. The findings demonstrate how the
      quality of patient-professional interaction influences patients' satisfaction
      with stroke rehabilitation. CONCLUSION: To be treated with respect and dignity
      seems to be a core element influencing vulnerable elderly stroke patients'
      satisfaction with rehabilitation. A merely functional definition of the success
      of rehabilitation should be expanded into an approach encompassing patients'
      perceptions and personal preferences. The meaning of dignity for elderly stroke
      patients in the rehabilitation setting should be further clarified and given
      practical substance.

PMID- 18728137
TI  - Neuropsychological predictors of powered wheelchair use: a prospective follow-up
      study.
AB  - OBJECTIVES: To investigate (1) rates of powered wheelchair use and level of user
      rated functional performance at one-month follow-up, and (2) whether
      psychological variables were prospectively predictive of outcome. DESIGN:
      Prospective follow-up study. SETTING: UK hospital-based regional rehabilitation
      and mobility centre. PARTICIPANTS: Volunteer adults with impaired mobility. Of
      155 approached, 103 had baseline assessments. Of these, 81 (79%) provided outcome
      data. Mean age was 65.6 years (SD = 13.5); 55% were male. MAIN OUTCOME MEASURES:
      Rate of day-to-day powerchair use, and users' perceptions of how well the
      powerchair allowed them to perform functional tasks. RESULTS: Among those with
      indoor-only chairs, 48% were 'less frequent' users; this rose to 72% among those
      with indoor/outdoor chairs. Excluding environmental reasons, rate of indoor use
      was predicted by baseline measures of verbal recall (P<0.001), figure copying
      (P=0.003) and global cognition (P=0.021). Among those with indoor/outdoor chairs,
      total rate of use was predicted by verbal recall (P= 0.001). Participants
      reported that the powerchair was effective in meeting their functional needs.
      CONCLUSIONS: Powered wheelchair use was predicted by cognitive measures. Rates of
      use were relatively low, despite users' reports that the powerchair facilitated
      their everyday functioning well.

PMID- 18728138
TI  - 'Show me, don't tell me'; is this a good approach for rehabilitation?
AB  - OBJECTIVE: To assess the possible memory advantages of the subject-performed task
      (SPT) and experimenter-performed task (EPT) encoding method in rehabilitation
      settings. DESIGN: Controlled quasi-experimental trial. SETTING: University
      research laboratory and community setting. SUBJECTS: Eighteen stroke survivors
      and 18 age-, education- and gender-matched controls. INTERVENTION: Participants
      were instructed to study three lists of 20 action phrases (such as 'ring the
      bell') by either reading, performing or observing others perform the tasks for
      later memory assessment. MAIN MEASURE: After the phrases had been studied, verbal
      and written memory tests were implemented and responses were recorded. RESULTS:
      The memory performance of stroke survivors and control groups was significantly
      better under the SPT method (mean (SD) 7.95 (2.7)) and EPT method (mean (SD) 7.95
      (2.5)) relative to the baseline verbal task method (mean (SD) 4.2 (1.9)),
      (P<0.001 ANOVA). Participants also remembered functional tasks better than
      clinical tasks (P<0.001 ANOVA). CONCLUSION: Encoding by the SPT and EPT methods
      are significantly more effective than receiving verbal instructions. The SPT and
      EPT encoding methods show promise and therapists may be able to use them in the
      clinic to facilitate the memory performance of stroke survivors.

PMID- 18728140
TI  - Healthcare for all: but what will intellectual disability services do now?

PMID- 18728141
TI  - Mountaineering expedition by persons with intellectual disability: impact on
      behavior and temperament.
AB  - The recreational needs of adults with intellectual disability are the same as
      those of the general population. If properly planned, recreational activities can
      facilitate positive behavioral changes. In this context, this present study was
      designed to understand the effects of a mountaineering expedition on the
      behaviors and temperament in a group of people with intellectual disability. The
      study included eight men and two women with intellectual disability aged 17-38
      years. After a training programme, the participants went on an 11 day expedition
      in the Himalayan region under the supervision of professionals and two parents.
      Results indicated that all of them successfully climbed mountains up to 12,000
      feet, and also had specific positive behavioral changes. Details and implications
      are discussed in this article.

PMID- 18728142
TI  - Women with and without intellectual disability and psychiatric disorders: an
      examination of the literature.
AB  - This article examines the literature on women with and without intellectual
      disability and psychiatric disorders, using a gender social model of health.
      Relevant empirical studies, international literature reviews and policies between
      1980 and 2007 were identified from electronic databases, journals and secondary
      sources. Three areas were examined: psychiatric disorders, their contextual
      background, and their clinical presentation. There are minimal levels of research
      into women with intellectual disability and psychiatric disorders. However, this
      article hypothesizes that women with intellectual disability have higher rates of
      psychiatric disorders than women without. This may result from greater
      vulnerability related both to internal factors (;intra': cognitive deficits,
      poorer communication skills, limited social skills) and to the external world
      (;inter': lack of opportunities, stigma, poor social support networks). The
      article argues that such women require gender-sensitive mental health services.
      However, more empirical evidence is required to support this claim and to inform
      development and delivery of services.

PMID- 18728143
TI  - The views and experiences of people with intellectual disabilities concerning
      advocacy: a focus group study.
AB  - This article discusses the first stage of a grounded theory study in which people
      with intellectual disabilities participated in focus groups to explore their
      definitions of advocacy and their advocacy support needs. Participants' ideas
      were influenced by their situation, the availability and type of support offered,
      and their relationships with supporters. Many different definitions of advocacy
      were revealed which were classified as reactive or proactive advocacy at micro,
      meso or macro level. The aim of advocacy was seen as empowerment, but this
      occurred only when support was readily available, concentrated on people's
      abilities, and facilitated opportunities for them to exert maximum possible
      control over their lives.

PMID- 18728144
TI  - Service users and staff from secure intellectual disability settings: views on
      three physical restraint procedures.
AB  - The appropriateness of and justification for physical restraint procedures in
      intellectual disabilities settings is an emotive issue. It creates a number of
      ethical dilemmas for nursing staff. This article examines the views of service
      users and nursing staff from secure residential facilities where restraint is
      used frequently. Both groups were asked to rate three videotaped restraint
      procedures for their acceptability. There were no significant differences between
      the two groups in the acceptability ratings of the methods of restraint. Service
      users were then interviewed about their restraint experiences. They reported
      feeling very angry, sad, stressed and confused and not at all happy or relaxed
      when being restrained. Scores indicated that participants were significantly
      happier and less stressed after restraint than during restraint.

PMID- 18728145
TI  - Examining pre-retirement and related services offered to service-users with an
      intellectual disability in Ireland.
AB  - The purpose of this study was to describe the pre-retirement and related services
      offered to service-users with intellectual disability in Ireland. Increasing
      numbers of service-users with an intellectual disability are living into older
      adulthood, creating important challenges for services providers. The National
      Intellectual Disability Database 2007 (NIDD) suggests that the population of
      service-users with an intellectual disability in the Republic of Ireland is an
      ageing population. Significant ongoing demands for new retirement-related
      intellectual disability services and enhancement of existing services are
      indicated. It is unknown how to support the development of a retirement policy to
      meet this growing need. The findings of this survey study indicate that there is,
      in general, recognition among Ireland's service providers of the need for
      retirement options for this population, although little attention has been
      directed towards formalizing these services through policy-making. There are few
      retirement policies in place, limiting the implementation of comprehensive
      services to meet the changing needs of ageing adults with an intellectual
      disability.

PMID- 18728146
TI  - Asbestos-related diseases: time for technology sharing.

PMID- 18728147
TI  - Sir Jacob Epstein, torso in metal from rock drill (1913-1914). Sculpture bronze
      object: 705 x 584 x 445 mm. Tate Britain, London.

PMID- 18728148
TI  - Occupational medicine in Canada.

PMID- 18728150
TI  - The Orebro musculoskeletal pain questionnaire.

PMID- 18728151
TI  - Novel human neutrophil agonistic properties of arsenic trioxide: involvement of
      p38 mitogen-activated protein kinase and/or c-jun NH2-terminal MAPK but not
      extracellular signal-regulated kinases-1/2.
AB  - Arsenic trioxide (ATO) is known for treating acute promyelocytic leukemia and for
      inducing apoptosis and mitogen-activated protein kinases (MAPKs) in promyelocytes
      and cancer cells. We recently reported that ATO induces neutrophil apoptosis. The
      aim of this study was to establish whether or not ATO recruits MAPKs in
      neutrophils, as well as to further investigate its agonistic properties. We found
      that ATO activates p38 and that, unlike H2O2, this response was not inhibited by
      exogenous catalase. Also, we demonstrated that ATO-induced p38 activation occurs
      before H2O2 generation and without a calcium burst. We next established that ATO
      recruits c-jun NH2-terminal (JNK) but not extracellular signal-regulated kinase 1
      and 2 (Erk-1/2). Using pharmacological inhibitors, we found that the proapoptotic
      activity of ATO occurs by a MAPK-independent mechanism. In contrast, the ability
      of ATO to enhance adhesion, migration, phagocytosis, release, and activity of
      gelatinase and degranulation of secretory, specific, and gelatinase, but not
      azurophilic granules, is dependent upon activation of p38 and/or JNK. This is the
      first study establishing that ATO possesses important agonistic properties in
      human neutrophils. Given the central role of neutrophils in various inflammatory
      disorders, we propose that ATO might have broader therapeutic implications in
      clinics, especially for regulating inflammation.

PMID- 18728152
TI  - Pharmacological treatment of alcohol hallucinosis.

PMID- 18728153
TI  - Renal endothelial function and blood flow predict the individual susceptibility
      to adriamycin-induced renal damage.
AB  - BACKGROUND: Susceptibility to renal injury varies among individuals. Previously,
      we found that individual endothelial function of healthy renal arteries in vitro
      predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized
      that individual differences in endothelial function in vitro and renal perfusion
      in vivo predict the severity of renal damage in a model of adriamycin-induced
      nephropathy. METHODS: In three separate studies, the following baseline
      parameters were measured in healthy male Wistar rats: (1) acetylcholine (ACh)
      induced relaxation in small renal arteries in vitro (n = 16) and the contribution
      of prostaglandins, nitric oxide (NO) and endothelium-dependent hyperpolarizing
      factor (EDHF) to the relaxation; (2) glomerular filtration rate (GFR) and
      effective renal plasma flow (ERPF) in spontaneously voiding rats in vivo (n = 16)
      and (3) the acute effect of the NO-synthase inhibitor N(G)-nitro-l-arginine
      methyl ester (L-NAME, n = 12) on renal blood flow (RBF) as compared to vehicle
      infusion (n = 9). Following these measurements, adriamycin (1.75 mg/kg i.v.) was
      injected and subsequent renal damage after 6 weeks was related to the baseline
      parameters. RESULTS: Total ACh-induced (r = 0.51, P < 0.05) and EDHF-mediated
      relaxation (r = 0.68, P < 0.05), as well as ERPF (r = 0.66, P < 0.01), positively
      correlated with the severity of proteinuria 6 weeks after injection. In contrast,
      pronounced baseline NO-mediated dilation was associated with lower proteinuria (r
      = 0.71, P < 0.01). Nevertheless, an acute L-NAME infusion, strongly reducing RBF
      by 22 +/- 8%, during adriamycin administration provided protection against the
      development of proteinuria. CONCLUSIONS: Individual animals with pronounced
      baseline endothelial dilatory ability measured in vitro and high ERPF in vivo are
      vulnerable to renal damage after the adriamycin injection. Acute inhibition of NO
      during adriamycin administration, resulting in a decrease of RBF, protects
      against renal injury, probably by limiting the delivery of the drug to the
      kidney. Therefore, interindividual variability in renal haemodynamics might be
      crucially involved in susceptibility to nephrotoxic renal damage.

PMID- 18728154
TI  - Heart rate variability (HRV) in kidney failure: measurement and consequences of
      reduced HRV.

PMID- 18728155
TI  - ABO blood group-incompatible living donor kidney transplantation: a prospective,
      single-centre analysis including serial protocol biopsies.
AB  - BACKGROUND: ABO incompatible kidney transplantation using antigen-specific
      immunoadsorption is increasingly performed but data on outcome, complications and
      protocol biopsies are still scarce. The present prospective single-centre study
      was aimed at these issues. METHODS: This was a prospective single-centre cohort
      study of 10 successive ABO incompatible living donor kidney transplantations at
      the University Hospital Basel from September 2005 to October 2007. The following
      parameters were closely monitored during the whole follow-up: graft function,
      albuminuria, blood group antibody titres, CD19+ cell count, total IgG and IgG
      subclasses, CMV antigenaemia, decoy cells in the urine, EBV and polyoma BK virus
      PCR in the blood. Protocol biopsies were performed on Days 0 and 7 after 3, 6, 12
      and 18 months. RESULTS: Patient and graft survival is 100% after a median follow
      up of 489 days (range 183-916 days). Median serum creatinine is 137 micromol/l
      (range 70-215 micromol/l), and median urine albumin-creatinine ratio (UACR) is
      3.1 mg/ mmol (range 0.6-7.8 mg/mmol) at the time of the last follow-up. All
      patients had sustained diminished CD19+ cell count and/or total IgG
      concentrations. Neither CMV antigenaemia nor EBV replication in the blood was
      observed. Seven patients had positive polyoma BK virus replication in the blood
      but none developed polyoma virus-associated nephropathy (PVAN). Protocol biopsies
      revealed rejection Banff IIa in three patients on Day 7, and in one patient after
      3 and 6 months. Banff Ia rejection was found in five patients. All rejection
      episodes resolved. Mild signs of chronic antibody-mediated rejection were
      observed in five patients. CONCLUSIONS: ABO-incompatible kidney transplantation
      seems to be successful and safe. Modifications of the current protocol may be
      possible and may further reduce potential side effects and costs.

PMID- 18728156
TI  - Renal dysfunction in acute stroke: an independent predictor of long-term all
      combined vascular events and overall mortality.
AB  - BACKGROUND: Acute stroke is the third leading cause of death in western societies
      after ischemic heart disease and cancer. Although it is an emergency disease
      sharing the same atherosclerotic risk factors with ischemic heart disease, the
      association of renal function and stroke is poorly investigated. The present
      study aims at assessing renal function status in patients with acute stroke and
      investigate any prognostic significance on the outcome. METHODS: This is a
      prospective study of hospitalized first-ever stroke patients over 10 years. The
      study population comprised 1350 patients admitted within 24 h from stroke onset
      and followed up for 1 to 120 months or until death. Patients were divided in 3
      groups on the basis of the estimated Glomerular Filtration Rate (eGFR) that was
      calculated from the abbreviated equation of the Modification Diet for Renal
      Disease in ml/min/1.73 m(2) of body surface area: Group-A comprised patients who
      had eGFR > 60, group-B those with 30 <or= eGFR <or= 60 and group-C patients with
      eGFR < 30. Patients with Acute Kidney Injury (AKI) were excluded from the study.
      The main outcome measures were overall mortality and the composite new
      cardiovascular events (myocardial infarction, recurrent stroke, vascular death)
      among the 3 groups during the follow-up period. RESULTS: Almost 1/3 (28.08%) of
      our acute stroke patients presented with moderate (group B) or severe (group C)
      renal dysfunction as estimated by eGFR. After adjusting for basic demographic,
      stroke risk factors and stroke severity on admission, eGFR was an independent
      predictor of stroke mortality at 10 years. Patients in groups B and C had an
      increased probability of death during follow-up: Hazard ratio = 1.21 with 95% CI
      1.01-1.46, p < 0.05 and Hazard ratio = 1.76 with 95% CI 1.14-2.73, p < 0.05
      respectively, compared to patients belonging to group A. The probability of death
      from any cause was significantly different among groups (log rank test 55.4, p =
      0.001) during the follow-up period: in group-A patients it was 62.8 (95% CI 57.6
      68.1), in group-B 77.3 (95% CI 68.5-86.1) and in group-C 89.2 (95% CI 75.1-100).
      During the follow-up period 336 new cardiovascular events occurred. The
      probability to have a new composite cardiovascular event was also significantly
      different among the 3 groups (log rank test 21.1, p = 0.001): in group-A patients
      it was 45.2 (95% CI 38.7-51.7), in group-B 67.4 (95% CI 56.2-78.6) and in group-C
      77.6 (95% CI 53.5-100). CONCLUSION: Renal function on admission appears to be a
      significant independent prognostic factor for long term mortality and new
      cardiovascular morbidity over a 10-year period.

PMID- 18728157
TI  - Calcimimetics, calcium set point and calcium balance.

PMID- 18728158
TI  - Estradiol supplementation in postmenopausal women attenuates suppression of
      pulsatile growth hormone secretion by recombinant human insulin-like growth
      factor type I.
AB  - BACKGROUND: Why pulsatile GH secretion declines in estrogen-deficient
      postmenopausal individuals remains unknown. One possibility is that estrogen not
      only enhances stimulation by secretagogues but also attenuates negative feedback
      by systemic IGF-I. SITE: The study took place at an academic medical center.
      SUBJECTS: Subjects were healthy postmenopausal women (n=25). METHODS: The study
      included randomized assignment to estradiol (n=13) or placebo (n=12)
      administration for 16 d and randomly ordered administration of 0, 1.0, 1.5, and
      2.0 mg/m2 recombinant human IGF-I sc on separate days fasting. ANALYSIS:
      Deconvolution analysis of pulsatile and basal GH secretion and approximate
      entropy (pattern-regularity) analysis were done to quantify feedback effects of
      IGF-I. OUTCOMES: Recombinant human IGF-I injections increased mean and peak serum
      IGF-I concentrations dose dependently (P<0.001) and suppressed mean GH
      concentrations (P<0.001), pulsatile GH secretion (P=0.001), and approximate
      entropy (P<0.001). Decreased GH secretion was due to reduced secretory-burst mass
      (P=0.005) and frequency (P<0.001) but not basal GH release (P=0.52). Estradiol
      supplementation lowered endogenous, but did not alter infused, IGF-I
      concentrations while elevating mean GH concentrations (P=0.012) and stimulating
      pulsatile (P=0.008) and basal (P<0.001) GH secretion. Estrogen attenuated IGF-I's
      inhibition of pulsatile GH secretion (P=0.042) but was unable to restore
      physiological GH pulse frequency or normalize approximate entropy. CONCLUSION:
      Short-term estrogen replacement in postmenopausal women selectively mutes IGF-I
      mediated feedback on pulsatile GH secretion. Disinhibition of negative feedback
      thus confers a novel mechanism by which estrogen may obviate hyposomatotropism.

PMID- 18728159
TI  - Fetuin-A and its relation to metabolic syndrome and fatty liver disease in obese
      children before and after weight loss.
AB  - CONTEXT: There are very limited data available concerning the relationships
      between fetuin-A, weight status, nonalcoholic fatty liver disease (NAFLD), and
      features of the metabolic syndrome (MetS) in obese humans, and especially in
      children. OBJECTIVE: Our objective was to study the longitudinal relationships
      between fetuin-A, NAFLD, and MetS in obese children. DESIGN: This was a 1-yr
      longitudinal follow-up study. SETTING: This study was performed in primary care.
      PATIENTS: A total of 36 obese and 14 lean children was included in the study.
      INTERVENTION: An outpatient 1-yr intervention program based on exercise,
      behavior, and nutrition therapy was performed. MAIN OUTCOME MEASURES: Changes of
      weight status (sd score-body mass index), waist circumference, fetuin-A, blood
      pressure, lipids, transaminases, insulin resistance index homeostasis model
      assessment (HOMA), and prevalence of NAFLD (defined by liver ultrasound) were
      calculated. RESULTS: The 12 obese children with NAFLD had significantly higher
      fetuin-A levels (0.35+/-0.07 g/liter) than the 24 obese children without NAFLD
      (0.29+/-0.06 g/liter) and the 14 normal weight children (0.29+/-0.05 g/liter).
      Fetuin-A levels were independent of age, pubertal stage, and gender. Fetuin-A
      correlated significantly to systolic (r=0.50) and diastolic blood pressure
      (r=0.41), insulin resistance index HOMA (r=0.28), and high-density lipoprotein
      cholesterol (r=-0.31). Changes of fetuin-A correlated significantly to changes of
      insulin resistance index HOMA (r=0.34), systolic (r=0.31) and diastolic blood
      pressure (r=0.37), and waist circumferences (r=0.36). Substantial weight loss in
      21 children led to a significant decrease of fetuin-A and the prevalence of NAFLD
      in contrast to the 15 children without substantial weight loss. CONCLUSIONS:
      Fetuin-A levels were higher in children with NAFLD, and were related to insulin
      resistance and to features of the MetS in both cross-sectional and longitudinal
      analyses. Therefore, fetuin-A might be a new promising link between obesity and
      its comorbidities.

PMID- 18728160
TI  - A novel dominant negative mutation of OTX2 associated with combined pituitary
      hormone deficiency.
AB  - CONTEXT: Combined pituitary hormone deficiency (CPHD) is characterized by
      deficiencies in more than one anterior pituitary hormone. Mutations in
      developmental factors responsible for pituitary cell specification and gene
      expression have been found in CPHD patients. OTX2, a bicoid class homeodomain
      protein, is necessary for both forebrain development and transactivation of the
      HESX1 promoter, but as of yet, has not been associated with CPHD. OBJECTIVE: The
      goal of this study was to identify and characterize novel mutations in pituitary
      specific transcription factors from CPHD patients. DESIGN: Genomic DNA was
      isolated from patients with hypopituitarism to amplify and sequence eight
      pituitary specific transcription factors (HESX1, LHX3, LHX4, OTX2, PITX2, POU1F1,
      PROP1, and SIX6). Characterization of novel mutations is based on structural and
      functional studies. RESULTS: We describe two unrelated children with CPHD who
      presented with neonatal hypoglycemia, and deficiencies of GH, TSH, LH, FSH, and
      ACTH. Magnetic resonance imaging revealed anterior pituitary hypoplasia with an
      ectopic posterior pituitary. A novel heterozygous OTX2 mutation (N233S) was
      identified. Wild-type and mutant OTX2 proteins bind equivalently to bicoid
      binding sites, whereas mutant OTX2 revealed decreased transactivation.
      CONCLUSIONS: A novel mutation in OTX2 binds normally to target genes and acts as
      a dominant negative inhibitor of HESX1 gene expression. This suggests that the
      expression of HESX1, required for spaciotemporal development of anterior
      pituitary cell types, when disrupted, results in an absent or underdeveloped
      anterior pituitary with diminished hormonal expression. These results demonstrate
      a novel mechanism for CPHD and extend our knowledge of the spectrum of gene
      mutations causing CPHD.

PMID- 18728161
TI  - Midnight salivary cortisol determination for assessing the outcome of
      transsphenoidal surgery in Cushing's disease.
AB  - CONTEXT: Midnight salivary cortisol (MSC) is now recognized as a reliable index
      for Cushing's syndrome diagnosis but has to be validated for the follow-up of
      treated patients. OBJECTIVE: Our objective was to evaluate MSC for assessing the
      outcome of transsphenoidal surgery (TSS) in patients with Cushing's disease (CD).
      DESIGN: We conducted a retrospective cohort study in a single center. PATIENTS
      AND METHODS: Sixty-eight patients treated by TSS between 1996 and 2006 and
      followed for at least 6 months with postoperative MSC were included. Mean follow
      up (+/- sd) was 45 +/- 31 months. Morning plasma cortisol was determined 5 d
      after TSS, and MSC and urinary cortisol (UC) were determined 6-12 months after
      surgery. The remission group included hypocortisolic (morning plasma cortisol <
      50 ng/ml and/or insufficient response to cosyntropin) and eucortisolic (midnight
      plasma cortisol < 75 ng/ml and normal UC) patients. Patients in the treatment
      failure group had high midnight plasma cortisol and UC concentrations. RESULTS:
      Fifty patients (74%) were in remission. Mean MSC was 0.7 +/- 0.4 ng/ml (range,
      0.4-2.1 ng/ml) and 6.5 +/- 6.5 ng/ml (range, 2.1-27.2 ng/ml) for the remission
      and treatment failure groups, respectively (P = 0.001). A cutoff of 2 ng/ml for
      MSC gave a sensitivity of 100% and a specificity of 98% for treatment failure
      diagnosis, whereas UC less than 90 microg/d had a sensitivity of 71% and
      specificity of 98%. Postsurgical morning plasma cortisol less than or equal to 18
      ng/ml had a sensitivity of 93% and specificity of 74%. CONCLUSIONS: MSC is a
      simple, robust marker of remission after TSS for CD.

PMID- 18728162
TI  - Plasma obestatin, ghrelin, and ghrelin/obestatin ratio are increased in
      underweight patients with anorexia nervosa but not in symptomatic patients with
      bulimia nervosa.
AB  - INTRODUCTION: Peptides of the gut-brain axis have a pivotal role in the
      regulation of energy homeostasis. Obestatin, a sibling of ghrelin derived from
      preproghrelin, is thought to oppose ghrelin effects on food intake. Because
      changes in ghrelin levels have been associated with anorexia nervosa (AN) and
      bulimia nervosa (BN), the investigation of obestatin production may further
      contribute to understanding the role of peripheral peptides in patients with
      eating disorders. METHODS: In the present study, we measured circulating blood
      levels of obestatin and ghrelin and assessed their relationships with
      anthropometric and clinical measures in 20 AN patients, 21 BN patients, and 20
      appropriate healthy controls. RESULTS: Compared with healthy women, patients with
      BN showed no significant differences in plasma obestatin and ghrelin
      concentrations and in the ghrelin/obestatin ratio, whereas underweight AN
      patients displayed significantly increased circulating levels of both obestatin
      (P<0.009) and ghrelin (P<0.002) and an increased ghrelin/obestatin ratio
      (P<0.04). Moreover, in AN women, positive correlations emerged between the
      ghrelin/obestatin ratio and current body weight and body mass index. CONCLUSIONS:
      Underweight AN patients are characterized by increased concentrations of ghrelin
      and obestatin and a higher ghrelin to obestatin ratio. No changes in circulating
      ghrelin or obestatin as well as in ghrelin to obestatin ratio seem to occur in
      acutely ill patients with BN. Although those changes likely reflect the
      physiological state of symptomatic AN individuals, they may also contribute to
      the pathophysiology of the disorder.

PMID- 18728163
TI  - Expression of glucocorticoid receptor messenger ribonucleic acid transcripts in
      the human placenta at term.
AB  - CONTEXT: Differential promoter use and alternative splicing generate a variety of
      glucocorticoid receptor (GR) mRNA transcripts, potentially altering the cortisol
      responsiveness of gestational tissues during pregnancy and labor. OBJECTIVE: We
      examined GR mRNA transcript expression in term placentae before and after labor,
      in association with fetal sex and after glucocorticoid treatment. DESIGN: RNA
      from 34 placentae and from eight placental explants incubated with
      glucocorticoids were analyzed for the GR mRNA variants GR-alpha, GR-beta, GR-P,
      and GR-gamma and the untranslated exon one variants 1A1, 1A2, 1A3, 1B, and 1C by
      quantitative RT-PCR. MAIN OUTCOME MEASURE: mRNA expression was assessed. RESULTS:
      All GR mRNA variants examined were detected in the human placenta, with GR-alpha
      and GR-1C mRNA having the highest expression of GR splice variants and exon 1
      variants, respectively. GR-P mRNA abundance decreased with spontaneous labor (P <
      0.01). GR-1A3 mRNA abundance changed with fetal sex, with a higher level in
      placentae of male fetuses (P < 0.05). GR-1C was the preferential promoter for GR
      alpha, GR-gamma, and GR-P mRNA. GR-beta mRNA was preferentially associated with
      GR-1A1. GR-P mRNA transcription switched to the GR-1A1 promoter after labor and
      to the GR-1A3 promoter in placentae from male fetuses. Glucocorticoid treatment
      significantly reduced transcription from promoters GR-1B and -1C and decreased GR
      alpha and GR-P mRNA abundance. CONCLUSIONS: The human placenta expresses a
      variety of GR mRNA transcripts. GR-alpha mRNA transcribed from the 1C promoter
      generates the majority of placental GR. However, alterations in promoter use and
      alternative splicing may modulate responses to cortisol during stressful events.

PMID- 18728164
TI  - Endoplasmic reticulum stress markers are associated with obesity in nondiabetic
      subjects.
AB  - OBJECTIVE: Adipocyte and hepatocyte endoplasmic reticulum (ER) stress response is
      activated in dietary and genetic models of obesity in mice. We hypothesized that
      ER stress was also activated and associated with reduced insulin sensitivity (SI)
      in human obesity. RESEARCH DESIGN AND METHODS: We recruited 78 healthy,
      nondiabetic individuals over a spectrum of body mass index (BMI) who underwent
      oral and iv glucose tolerance tests, and fasting sc adipose and muscle biopsies.
      We tested expression of 18 genes and levels of total and phosphorylated
      eukaryotic initiation factor 2alpha, c-jun, and c-Jun N-terminal kinase 1 in
      adipose tissue. We compared gene expression in stromal vascular and adipocyte
      fractions in paired samples from 22 individuals, and tested clustering on gene
      and protein markers. RESULTS: Adipocyte expression of most markers of ER stress,
      including chaperones downstream of activating transcription factor 6, were
      significantly correlated with BMI and percent fat (r>0.5; P<0.00001).
      Phosphorylation of eukaryotic initiation factor 2alpha but not of c-Jun N
      terminal kinase 1 or c-jun was increased with obesity. ER stress response (as
      elsewhere) was also increased with obesity in a second set of 86 individuals, and
      in the combined sample (n=161). The increase was only partially attributable to
      the stromal vascular fraction and macrophage infiltration. ER stress markers were
      only modestly correlated with S(I). Clustering algorithms supported ER stress
      activation with high BMI but not low SI. CONCLUSIONS: Multiple markers of ER
      stress are activated in human adipose with obesity, particularly for protective
      chaperones downstream of activating transcription factor 6alpha.

PMID- 18728165
TI  - Severe obesity confounds the interpretation of low-dose dexamethasone test
      combined with the administration of ovine corticotrophin-releasing hormone in
      childhood Cushing syndrome.
AB  - CONTEXT: Suppression of cortisol secretion with a low-dose dexamethasone (Dex)
      followed by the administration of ovine CRH (Dex-oCRH) is used in the evaluation
      of adults with a pseudo-Cushing syndrome state (PCSS) vs. Cushing syndrome (CS).
      OBJECTIVE: The aim of the study was to determine the value of Dex-oCRH testing in
      the investigation of childhood CS. DESIGN: We conducted a retrospective analysis
      of data from children evaluated for CS vs. PCSS from 1998-2006; body mass index Z
      (BMIZ) and height-for-age Z (HAZ) scores were estimated. SETTING: A clinical
      research center was the setting for the study. MAIN OUTCOME MEASURES: The main
      outcomes were confirmation of the diagnosis of CS by histology and response to
      Dex-oCRH. RESULTS: Thirty-two children (ages 3-17 yr) were studied: 11 had CS and
      21 had PCSS; of the latter, 11 had a BMIZ score greater than 2. Children with CS
      had a mean HAZ score of -1.3+/-0.51 vs. 0.31+/-0.38 in nonobese and 0.71+/-0.39
      in obese children (P<0.001). The previously established criterion of a cortisol
      of 1.4 microg/dl (38 nmol/liter) after Dex-oCRH identified all 10 normal children
      who were not very obese and those with CS; 5 of 11 normal children with more
      severe obesity had cortisol values greater than 1.4 microg/dl (38 nmol/liter)
      after Dex-oCRH, lowering the test specificity to 55%. Without consideration for
      obesity, an increase of the cutoff cortisol value after Dex-oCRH to 3.2 microg/dl
      (88 nmol/liter) will have 91% sensitivity and 95% specificity; the corresponding
      values for a cutoff of 2.2 microg/dl (61 nmol/liter) were 100 and 90.5%,
      respectively. CONCLUSION: Our study showed that height gain is a simple way of
      distinguishing children with PCCS from those with CS; the interpretation of Dex
      oCRH in children is confounded by severe obesity, which limits the utility of
      this test.

PMID- 18728166
TI  - Association studies of common variants in 10 hypogonadotropic hypogonadism genes
      with age at menarche.
AB  - CONTEXT: Although the timing of puberty is a highly heritable trait, little is
      known about the genes that regulate pubertal timing in the general population.
      Several genes have been identified that, when mutated, cause disorders of delayed
      or absent puberty such as hypogonadotropic hypogonadism (HH). OBJECTIVE: Because
      severe variants in HH-related genes cause a severe puberty phenotype, we
      hypothesized that common subtle variation in these genes could contribute to the
      population variation in pubertal timing. DESIGN: We assessed common genetic
      variation in 10 HH-related genes in 1801 women from the Hawaii and Los Angeles
      Multiethnic Cohort with either early (age<11 yr) or late (age>14 yr) menarche and
      in other replication samples. In addition to these common variants, we also
      studied the most frequently reported HH mutations to assess their role in the
      population variation in pubertal timing. SETTING AND PATIENTS/OTHER PARTICIPANTS:
      Within the general community, 1801 women from the Hawaii and Los Angeles
      Multiethnic Cohort participated. MAIN OUTCOME MEASURES: We assessed the
      association of genetic variation with age at menarche. RESULTS: We found no
      significant association between any of the variants tested and age at menarche,
      although we cannot rule out modest effects of these variants or of other variants
      at long distances from the coding region. In several self-reported racial/ethnic
      groups represented in our study, we observed an association between estimated
      genetic ancestry and age at menarche. CONCLUSIONS: Our results suggest that
      common variants near 10 HH-related loci do not play a substantial role in the
      regulation of age at menarche in the general population.

PMID- 18728167
TI  - Autoantibodies against type I interferons as an additional diagnostic criterion
      for autoimmune polyendocrine syndrome type I.
AB  - CONTEXT: In autoimmune polyendocrinopathy syndrome type I (APS-I), mutations in
      the autoimmune regulator gene (AIRE) impair thymic self-tolerance induction in
      developing T cells. The ensuing autoimmunity particularly targets ectodermal and
      endocrine tissues, but chronic candidiasis usually comes first. We recently
      reported apparently APS-I-specific high-titer neutralizing autoantibodies against
      type I interferons in 100% of Finnish and Norwegian patients, mainly with two
      prevalent AIRE truncations. OBJECTIVES: Because variability in clinical features
      and age at onset in APS-I frequently results in unusual presentations, we
      prospectively checked the diagnostic potential of anti-interferon antibodies in
      additional APS-I panels with other truncations or rare missense mutations and in
      disease controls with chronic mucocutaneous candidiasis (CMC) but without either
      common AIRE mutation. DESIGN: The study was designed to detect autoantibodies
      against interferon-alpha2 and interferon-omega in antiviral neutralization
      assays. SETTING AND PATIENTS: Patients included 14 British/Irish, 15 Sardinian,
      and 10 Southern Italian AIRE-mutant patients with APS-I; also 19 other patients
      with CMC, including four families with cosegregating thyroid autoimmunity.
      OUTCOME: The diagnostic value of anti-interferon autoantibodies was assessed.
      RESULTS: We found antibodies against interferon-alpha2 and/or interferon-omega in
      all 39 APS-I patients vs. zero of 48 unaffected relatives and zero of 19
      British/Irish CMC patients. Especially against interferon-omega, titers were
      nearly always high, regardless of the exact APS-I phenotype/duration or AIRE
      genotype, including 12 different AIRE length variants or 10 point substitutions
      overall (n=174 total). Strikingly, in one family with few typical APS-I features,
      these antibodies cosegregated over three generations with autoimmune
      hypothyroidism plus a dominant-negative G228W AIRE substitution. CONCLUSIONS:
      Otherwise restricted to patients with thymoma and/or myasthenia gravis, these
      precocious persistent antibodies show 98% or higher sensitivity and APS-I
      specificity and are thus a simpler diagnostic option than detecting AIRE
      mutations.

PMID- 18728168
TI  - Severe intrauterine growth retardation and atypical diabetes associated with a
      translocation breakpoint disrupting regulation of the insulin-like growth factor
      2 gene.
AB  - CONTEXT: IGF-II is an imprinted gene (predominantly transcribed from the
      paternally inherited allele), which has an important role in fetal growth in
      mice. IGF2 gene expression is regulated by a complex system of enhancers and
      promoters that determine tissue-specific and development-specific transcription.
      In mice, enhancers of the IGF2 gene are located up to 260 kb telomeric to the
      gene. The role of IGF-II in humans is unclear. OBJECTIVE: A woman of short adult
      stature (1.46 m, -3 sd score) born with severe intrauterine growth retardation
      (1.25 kg at term, -5.4 SD score) and atypical diabetes diagnosed at the age of 23
      yr had a balanced chromosomal translocation t(1;11) (p36.22; p15.5). We
      hypothesized that her phenotype resulted from disruption of her paternally
      derived IGF2 gene because her daughter who inherited the identical translocation
      had normal birth weight. DESIGN: Both chromosomal break points were identified
      using fluorescent in situ hybridization. Sequence, methylation, and expression of
      the IGF2 gene was examined. Hyperinsulinemic, euglycemic clamp with glucose
      tracers and magnetic resonance imaging of the thorax, abdomen, and pelvis were
      performed. RESULTS: The 11p15.5 break point mapped 184 kb telomeric of the IGF2
      gene. Microsatellite markers confirmed paternal origin of this chromosome. IGF2
      gene sequence and methylation was normal. IGF2 gene expression was reduced in
      lymphoblasts. Clamp studies showed marked hepatic and total insulin resistance.
      Massive excess sc fat was seen on magnetic resonance imaging despite slim body
      mass index (21.1 kg/m2). CONCLUSIONS: A break point 184 kb upstream of the
      paternally derived IGF2 gene, separating it from some telomeric enhancers,
      resulted in reduced expression in some mesoderm-derived adult tissues causing
      intrauterine growth retardation, short stature, lactation failure, and insulin
      resistance with altered fat distribution.

PMID- 18728169
TI  - Abdominal and gynoid fat mass are associated with cardiovascular risk factors in
      men and women.
AB  - CONTEXT: Abdominal obesity is an established risk factor for cardiovascular
      disease (CVD). However, the correlation of dual-energy x-ray absorptiometry
      (DEXA) measurements of regional fat mass with CVD risk factors has not been
      completely investigated. OBJECTIVE: The aim of this study was to investigate the
      association of estimated regional fat mass, measured with DEXA and CVD risk
      factors. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study of
      175 men and 417 women. DEXA measurements of regional fat mass were performed on
      all subjects, who subsequently participated in a community intervention program.
      MAIN OUTCOME MEASURES: Outcome measures included impaired glucose tolerance,
      hypercholesterolemia, hypertriglyceridemia, and hypertension. RESULTS: We began
      by assessing the associations of the adipose measures with the cardiovascular
      outcomes. After adjustment for confounders, a sd unit increase in abdominal fat
      mass was the strongest predictor of most cardiovascular variables in men [odds
      ratio (OR)=2.63-3.37; P<0.05], whereas the ratio of abdominal to gynoid fat mass
      was the strongest predictor in women (OR=1.48-2.19; P<0.05). Gynoid fat mass was
      positively associated with impaired glucose tolerance, hypertriglyceridemia, and
      hypertension in men (OR=2.07-2.15; P<0.05), whereas the ratio of gynoid to total
      fat mass showed a negative association with hypertriglyceridemia and hypertension
      (OR=0.42-0.62; P<0.005). CONCLUSIONS: Abdominal fat mass is strongly
      independently associated with CVD risk factors in the present study. In contrast,
      gynoid fat mass was positively associated, whereas the ratio of gynoid to total
      fat mass was negatively associated with risk factors for CVD.

PMID- 18728171
TI  - Persistence of an intact endometrial matrix and vessels structure in women
      exposed to VA-2914, a selective progesterone receptor modulator.
AB  - BACKGROUND: VA-2914 is a selective progesterone receptor modulator with potential
      contraceptive activity that induces amenorrhea, whereas progestins cause
      endometrial spotting and bleeding. This abnormal bleeding due to progestins is a
      consequence of focal stromal proteolysis by an increase in naked vessel size and
      density. OBJECTIVE: Our objective was to quantify the effects of VA-2914 on
      endometrial vascularization, fibrillar matrix, and vascular endothelial growth
      factor (VEGF)-A expression in endometrial biopsies from 41 women before and after
      12 wk daily treatment with a placebo, or 2.5, 5, or 10 mg VA-2914. METHODS:
      Collagen fibrillar network was stained by silver impregnation. Vessel area,
      density, and structure were quantified with a computer-assisted image analysis
      system after double immunostaining using an anti-von Willebrand factor
      (endothelial cells) and an anti-alpha smooth muscle actin (vascular smooth muscle
      cells) marker antibody. VEGF-A mRNAs were quantified by RT-PCR and localized by
      immunohistochemistry. RESULTS: The endometrial vessels, collagen network, and
      mRNA levels of VEGF-A were identical during the luteal phase at baseline and in
      VA-2914 treated women. VEGF-A distribution was unchanged. CONCLUSIONS: VA-2914
      does not alter the endometrial matrix and cells, and does not modify the
      endometrial vessel morphology as compared with baseline biopsies.

PMID- 18728172
TI  - Dose-dependent effect of growth hormone on final height in children with short
      stature without growth hormone deficiency.
AB  - CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially
      those with idiopathic short stature (ISS), has not been clearly established owing
      to the lack of controlled trials continuing until final height (FH). OBJECTIVE:
      The aim of the study was to investigate the effect on growth to FH of two GH
      doses given to short children, mainly with ISS, compared with untreated controls.
      DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was
      conducted in Sweden. INTERVENTION: Two doses of GH (Genotropin) were
      administered, 33 or 67 microg/kg.d; control subjects were untreated. SUBJECTS: A
      total of 177 subjects with short stature were enrolled. Of these, 151 were
      included in the intent to treat (AllITT) population, and 108 in the per protocol
      (AllPP) population. Analysis of ISS subjects included 126 children in the ITT
      (ISSITT) population and 68 subjects in the PP (ISSPP) population. MAIN OUTCOME
      MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral
      height (diff MPHSDS), and gain in heightSDS. RESULTS: After 5.9+/-1.1 yr on GH
      therapy, the FHSDS in the AllPP population treated with GH vs. controls was 
      1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86;
      P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/
      0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69
      (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A
      dose-response relationship identified after 1 yr remained to FH for all growth
      outcome variables in all four populations. CONCLUSION: GH treatment significantly
      increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3
      SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean
      gain of 0.2 SDS in the untreated controls.

PMID- 18728170
TI  - Relations between endogenous androgens and estrogens in postmenopausal women with
      suspected ischemic heart disease.
AB  - CONTEXT: Because androgens are obligatory precursors of estrogens, it is
      reasonable to assume that their serum concentrations would exhibit positive
      correlations. If so, then epidemiologic studies that examine the association
      between androgens and pathological processes should adjust the results for the
      independent effect of estrogens. OBJECTIVE: The objective of the study was to
      examine the interrelationships among testosterone (T), androstenedione, estradiol
      (E2), estrone, and SHBG in postmenopausal women. DESIGN: This was a cross
      sectional study of women participating in the National Heart, Blood, and Lung
      Institute-sponsored Women's Ischemia Syndrome Evaluation study. SETTING: The
      study was conducted at four academic medical centers. PATIENTS: A total of 284
      postmenopausal women with chest pain symptoms or suspected myocardial ischemia.
      MAIN OUTCOME MEASURES: Post hoc analysis of the relationships among sex steroid
      hormones with insulin resistance, body mass index (BMI), and presence or absence
      of coronary artery disease as determined by coronary angiography. RESULTS: BMI
      was significantly associated with insulin resistance, total E2, free E2,
      bioavailable E2, and free T. Highly significant correlations were found for total
      T, free T, and androstenedione with total E2, free E2, bioavailable E2, and
      estrone and persisted after adjustment for BMI and insulin resistance. A
      significant relationship was present between total and free T and the presence of
      coronary artery disease after adjustment for the effect of E2. CONCLUSIONS: Serum
      levels of androgens and estrogens track closely in postmenopausal women referred
      for coronary angiography for suspected myocardial ischemia. Epidemiological
      studies that relate sex steroid hormones to physiological or pathological
      processes need to control for the independent effect of both estrogens and
      androgens.

PMID- 18728173
TI  - Timing of pubertal onset in girls: evidence for non-Gaussian distribution.
AB  - CONTEXT: The timing of the onset of puberty is considered to approximate a normal
      distribution. However, because many more girls present with early than late
      puberty, we hypothesized that the distribution of the timing of the onset of
      puberty in girls might have changed. OBJECTIVE/SUBJECTS: The objective of the
      study was to examine the distribution of the timing of the onset of puberty in
      normal Greek girls. DESIGN: Onset of puberty, i.e. breast development (B2), was
      studied longitudinally in 311 prepubertal schoolgirls aged 6.4-8.2 yr until the
      onset of puberty. We also studied cross-sectionally 126 girls, 6-14 yr old.
      SETTING: Clinical examinations took place in the school setting. RESULTS: In the
      longitudinal study, median of the distribution of age at B2 was 10.0 yr (with the
      25th and 75th centiles being 9.2 and 10.6 yr, respectively). Skewness was -0.45
      (P=0.001), suggesting a negatively skewed distribution. In the cross-sectional
      study, 126 subjects were found at B2. The median of the age distribution at B2
      was 10.1 yr (with the 25th and 75th centiles being 9.7 and 11.2 years,
      respectively). Skewness was -0.44 (P=0.03), suggesting a negatively skewed
      distribution. CONCLUSIONS: A non-Gaussian distribution of the age at the onset of
      puberty in girls was documented. The currently used cutoff ages for precocious
      and delayed puberty may not be applicable to modern children; therefore, up-to
      date studies on pubertal maturation are much needed.

PMID- 18728174
TI  - Fat mass and apolipoprotein E genotype influence serum lipoprotein levels in
      early adulthood, whereas birth size does not.
AB  - BACKGROUND/OBJECTIVES: An association between an unfavorable lipid profile and
      low birth weight has been reported, although this association remains
      controversial. We hypothesized that birth size does not have any influence on
      serum lipid levels but fat accumulation during childhood has. METHODS: In the
      PROgramming factors for GRowth And Metabolism study, a cohort of 297 young
      adults, aged 18-24 yr, the influence of clinical parameters on total cholesterol,
      triglycerides, low-density lipoprotein, high-density lipoprotein, lipoprotein a,
      and apolipoprotein (apo) A-1 and apoB was analyzed with multiple regression
      modeling. In addition, differences in these lipid levels and ApoE genotype
      prevalence were analyzed in four subgroups: young adults either born small for
      gestational age with short stature or with catch-up growth, or born appropriate
      for gestational age with idiopathic short stature or with normal stature
      (controls). RESULTS: Birth length sd score (SDS) and birth weight SDS were no
      significant determinants of the serum lipid levels, whereas gender, ApoE
      genotype, adult height SDS, adult weight SDS, and fat mass were. Comparison of
      the subgroups showed that small for gestational age with short stature subjects
      had a significantly higher apoB than controls. There were no other significant
      differences in lipid levels or ApoE genotype prevalence among the four subgroups.
      CONCLUSIONS: ApoE genotype is an important genetic determinant of lipid levels in
      young adulthood. Furthermore, fat accumulation during childhood significantly
      determines serum lipid levels, whereas birth size has no significant
      contribution. For public health practice, this means that parents and their
      children need to be informed about the risks of fat accumulation during
      childhood.

PMID- 18728176
TI  - Thyroid hormones directly alter human hair follicle functions: anagen
      prolongation and stimulation of both hair matrix keratinocyte proliferation and
      hair pigmentation.
AB  - CONTEXT: Both insufficient and excess levels of thyroid hormones (T3 and T4) can
      result in altered hair/skin structure and function (e.g. effluvium). However, it
      is still unclear whether T3 and T4 exert any direct effects on human hair
      follicles (HFs), and if so, how exactly human HFs respond to T3/T4 stimulation.
      OBJECTIVE: Our objective was to asses the impact of T3/T4 on human HF in vitro.
      METHODS: Human anagen HFs were isolated from skin obtained from females
      undergoing facelift surgery. HFs from euthyroid females between 40 and 69 yr
      (average, 56 yr) were cultured and treated with T3/T4. RESULTS: Studying
      microdissected, organ-cultured normal human scalp HFs, we show here that T4 up
      regulates the proliferation of hair matrix keratinocytes, whereas their apoptosis
      is down-regulated by T3 and T4. T4 also prolongs the duration of the hair growth
      phase (anagen) in vitro, possibly due to the down-regulation of TGF-beta2, the
      key anagen-inhibitory growth factor. Because we show here that human HFs
      transcribe deiodinase genes (D2 and D3), they may be capable of converting T4 to
      T3. Intrafollicular immunoreactivity for the recognized thyroid hormone
      responsive keratins cytokeratin (CK) 6 and CK14 is significantly modulated by T3
      and T4 (CK6 is enhanced, CK14 down-regulated). Both T3 and T4 also significantly
      stimulate intrafollicular melanin synthesis. CONCLUSIONS: Thus, we present the
      first evidence that human HFs are direct targets of thyroid hormones and
      demonstrate that T3 and/or T4 modulate multiple hair biology parameters, ranging
      from HF cycling to pigmentation.

PMID- 18728175
TI  - The impact of metformin, oral contraceptives, and lifestyle modification on
      polycystic ovary syndrome in obese adolescent women in two randomized, placebo
      controlled clinical trials.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) presents in adolescence, and obesity is
      a common finding. The benefits and risks of alternate approaches to the
      management of PCOS in obese adolescent women are not clear. OBJECTIVE: We
      investigated the effects of metformin, oral contraceptives (OCs), and/or
      lifestyle modification in obese adolescent women with PCOS. DESIGN: Two small,
      randomized, placebo-controlled clinical trials were performed. PATIENTS AND
      PARTICIPANTS: A total of 79 obese adolescent women with PCOS participated.
      INTERVENTIONS: In the single treatment trial, subjects were randomized to
      metformin, placebo, a lifestyle modification program, or OC. In the combined
      treatment trial, all subjects received lifestyle modification and OC and were
      randomized to metformin or placebo. MAIN OUTCOME MEASURES: Serum concentrations
      of androgens and lipids were measured. RESULTS: Lifestyle modification alone
      resulted in a 59% reduction in free androgen index with a 122% increase in SHBG.
      OC resulted in a significant decrease in total testosterone (44%) and free
      androgen index (86%) but also resulted in an increase in C-reactive protein
      (39.7%) and cholesterol (14%). The combination of lifestyle modification, OC, and
      metformin resulted in a 55% decrease in total testosterone, as compared to 33%
      with combined treatment and placebo, a 4% reduction in waist circumference, and a
      significant increase in HDL (46%). CONCLUSIONS: In these preliminary trials, both
      lifestyle modification and OCs significantly reduce androgens and increase SHBG
      in obese adolescents with PCOS. Metformin, in combination with lifestyle
      modification and OC, reduces central adiposity, reduces total testosterone, and
      increases HDL, but does not enhance overall weight reduction.

PMID- 18728177
TI  - A large-scale genome-wide linkage analysis to map loci linked to stature in
      Chinese population.
AB  - CONTEXT: A number of genome-wide scans of stature have been reported previously,
      but with inconsistent results. The inconsistency may be partly due to
      differential population characteristics and gender- and/or age-specific effects
      on this trait. OBJECTIVE: This study aimed to identify the quantitative trait
      loci (QTLs) underlying the variation of stature in Chinese population, and to
      evaluate age- and gender-specific linkage for stature. METHODS: We conducted a
      large-scale, genome-wide linkage scan using the data from three independent
      samples (a total of 7112 subjects from 1811 pedigrees) enrolled from the same
      geographical region in China. Linkage analyses were performed in the pooled
      samples and in subgroups defined by age (<or=25 vs. >25 yr), gender, or both,
      using the model-free regression method implemented in MERLIN-REGRESS. RESULTS:
      The strongest linkage signal was obtained on 17q24 (LOD=3.82) in the pooled
      samples. Age-specific analysis revealed two additional significant QTLs on 13q34
      and 18p11.3 among subjects 25 yr or younger. In gender-specific analyses, males
      showed suggestive QTLs on 12q21 (LOD=2.31) and 17q22 (LOD=2.60), and females
      showed a suggestive QTL on 13q31.1 (LOD=2.68). Age- and gender-specific linkage
      analyses suggested that males older than 25 yr contributed more signals to QTLs
      on 12q21 and 17q22, with a LOD score of 3.00 and 2.26, respectively, whereas
      females older than 25 yr presented a suggestive QTL on 8q24.3 (LOD=2.57).
      CONCLUSION: Our study identified a strong linkage of chromosome 17q24 to stature
      in this Chinese population, and indicated that it may be informative to consider
      differential age and gender effects in the genetic dissection of stature.

PMID- 18728178
TI  - Unraveling the molecular basis of subunit specificity in P pilus assembly by mass
      spectrometry.
AB  - P pili are multisubunit fibers essential for the attachment of uropathogenic
      Escherichia coli to the kidney. These fibers are formed by the noncovalent
      assembly of six different homologous subunit types in an array that is strictly
      defined in terms of both the number and order of each subunit type. Assembly
      occurs through a mechanism termed "donor-strand exchange (DSE)" in which an N
      terminal extension (Nte) of one subunit donates a beta-strand to an adjacent
      subunit, completing its Ig fold. Despite structural determination of the
      different subunits, the mechanism determining specificity of subunit ordering in
      pilus assembly remained unclear. Here, we have used noncovalent mass spectrometry
      to monitor DSE between all 30 possible pairs of P pilus subunits and their Ntes.
      We demonstrate a striking correlation between the natural order of subunits in
      pili and their ability to undergo DSE in vitro. The results reveal insights into
      the molecular mechanism by which subunit ordering during the assembly of this
      complex is achieved.

PMID- 18728179
TI  - Functional disturbances in the striatum by region-specific ablation of NMDA
      receptors.
AB  - To study the role of NMDA receptors in dopamine signaling of the striatum, the
      brain area that receives glutamatergic inputs from various cortical areas and
      most dopaminergic inputs, we generated striatum-specific NMDA receptor-deficient
      mice. The mutant pups showed reduced food intake and retarded growth starting at
      the second postnatal week and died on approximately postnatal day 20 (P20). The
      time course of postnatal lethality is similar to that of compound mutant, double
      knockout of dopamine D1/D2 receptors, or genetically engineered dopamine
      deficient mouse. In vivo electrophysiological recordings in the mutant pups
      showed that frequencies in the range of gamma oscillation were reduced in the
      striatal circuits. Moreover, the number of functional dopamine receptors in the
      striatum as measured by D1- and D2-binding experiments was greatly diminished in
      the mutants as compared with control animals. A consequence of diminished
      dopamine binding in the striatum manifested in an increase of locomotor activity.
      The administration of D1/D2 agonists paradoxically reduced the hyperactivity of
      the mutant mice as compared with an increase in locomotor activity in control
      mice. These results demonstrate that the NMDA receptor plays an essential role in
      the integration of dopamine signaling in the striatum and that is required in
      behavioral function.

PMID- 18728180
TI  - Cell cycle progression requires the CDC-48UFD-1/NPL-4 complex for efficient DNA
      replication.
AB  - Since cdc48 mutants were isolated by the first genetic screens for cell division
      cycle (cdc) mutants in yeast, the requirement of the chaperone-like ATPase
      Cdc48/p97 during cell division has remained unclear. Here, we discover an
      unanticipated function for Caenorhabditis elegans CDC-48 in DNA replication
      linked to cell cycle control. Our analysis of the CDC-48(UFD-1/NPL-4) complex
      identified a general role in S phase progression of mitotic cells essential for
      embryonic cell division and germline development of adult worms. These
      developmental defects result from activation of the DNA replication checkpoint
      caused by replication stress. Similar to loss of replication licensing factors,
      DNA content is strongly reduced in worms depleted for CDC-48, UFD-1, and NPL-4.
      In addition, these worms show decreased DNA synthesis and hypersensitivity toward
      replication blocking agents. Our findings identified a role for CDC-48(UFD-1/NPL
      4) in DNA replication, which is important for cell cycle progression and genome
      stability.

PMID- 18728181
TI  - The day/night switch in KaiC, a central oscillator component of the circadian
      clock of cyanobacteria.
AB  - The circadian oscillator of the cyanobacterium Synechococcus elongatus is
      composed of only three proteins, KaiA, KaiB, and KaiC, which, together with ATP,
      can generate a self-sustained approximately 24 h oscillation of KaiC
      phosphorylation for several days. KaiA induces KaiC to autophosphorylate, whereas
      KaiB blocks the stimulation of KaiC by KaiA, which allows KaiC to
      autodephosphorylate. We propose and support a model in which the C-terminal loops
      of KaiC, the "A-loops", are the master switch that determines overall KaiC
      activity. When the A-loops are in their buried state, KaiC is an autophosphatase.
      When the A-loops are exposed, however, KaiC is an autokinase. A dynamic
      equilibrium likely exists between the buried and exposed states, which determines
      the steady-state level of phosphorylation of KaiC. The data suggest that KaiA
      stabilizes the exposed state of the A-loops through direct binding. We also show
      evidence that if KaiA cannot stabilize the exposed state, KaiC remains
      hypophosphorylated. We propose that KaiB inactivates KaiA by preventing it from
      stabilizing the exposed state of the A-loops. Thus, KaiA and KaiB likely act by
      shifting the dynamic equilibrium of the A-loops between exposed and buried
      states, which shifts the balance of autokinase and autophosphatase activities of
      KaiC. A-loop exposure likely moves the ATP closer to the sites of
      phosphorylation, and we show evidence in support of how this movement may be
      accomplished.

PMID- 18728182
TI  - MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis.
AB  - Progress in understanding the biology of multiple myeloma (MM), a plasma cell
      malignancy, has been slow. The discovery of microRNAs (miRNAs), a class of small
      noncoding RNAs targeting multiple mRNAs, has revealed a new level of gene
      expression regulation. To determine whether miRNAs play a role in the malignant
      transformation of plasma cells (PCs), we have used both miRNA microarrays and
      quantitative real time PCR to profile miRNA expression in MM-derived cell lines
      (n = 49) and CD138+ bone marrow PCs from subjects with MM (n = 16), monoclonal
      gammopathy of undetermined significance (MGUS) (n = 6), and normal donors (n =
      6). We identified overexpression of miR-21, miR-106b approximately 25 cluster,
      miR-181a and b in MM and MGUS samples with respect to healthy PCs. Selective up
      regulation of miR-32 and miR-17 approximately 92 cluster was identified in MM
      subjects and cell lines but not in MGUS subjects or healthy PCs. Furthermore, two
      miRNAs, miR-19a and 19b, that are part of the miR-17 approximately 92 cluster,
      were shown to down regulate expression of SOCS-1, a gene frequently silenced in
      MM that plays a critical role as inhibitor of IL-6 growth signaling. We also
      identified p300-CBP-associated factor, a gene involved in p53 regulation, as a
      bona fide target of the miR106b approximately 25 cluster, miR-181a and b, and miR
      32. Xenograft studies using human MM cell lines treated with miR-19a and b, and
      miR-181a and b antagonists resulted in significant suppression of tumor growth in
      nude mice. In summary, we have described a MM miRNA signature, which includes
      miRNAs that modulate the expression of proteins critical to myeloma pathogenesis.

PMID- 18728183
TI  - Identification of two major types of age-associated CD8 clonal expansions with
      highly divergent properties.
AB  - CD8 memory T cells are tightly regulated in young, healthy individuals but are
      often perturbed in aged animals by the appearance of large CD8 T cell clones.
      These clones are associated with impaired immunity in the aged. The molecular
      basis of this phenomenon remains unclear. Here, it is shown that the issue is
      confused by the fact that the clones are heterogeneous. Some clones bear high,
      and others, low levels of integrin alpha(4) (itgalpha4). These subtypes differ by
      multiple criteria. They appear in mice of different ages, concentrate in
      different tissues, and have different stabilities in vivo and responses to
      stimulation in vitro. itgalpha4(high), but not itgalpha4(low), CD8 clonal
      expansions have several characteristics consistent with a chronically stimulated
      phenotype. These properties include lowered levels of CD8, decreased expression
      of some cytokine receptors, and elevated expression of various inhibitory
      receptors, including the programmed death-1 (PD1) receptor and the killer cell
      lectin-like receptor G1 (KLRG1). The characteristics of itgalpha4(high) clonal
      expansions suggest that they may arise from age-dependent alterations in antigen
      expression and tolerance. These data redefine CD8 clonal expansions into at least
      two distinct entities and indicate that there are multiple mechanisms that drive
      age-related alterations of CD8 T cell homeostasis.

PMID- 18728184
TI  - Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of
      very long chain fatty acids.
AB  - Stargardt-like macular dystrophy (STGD3) is a dominantly inherited juvenile
      macular degeneration that eventually leads to loss of vision. Three independent
      mutations causing STGD3 have been identified in exon six of a gene named
      Elongation of very long chain fatty acids 4 (ELOVL4). The ELOVL4 protein was
      predicted to be involved in fatty acid elongation, although evidence for this and
      the specific step(s) it may catalyze have remained elusive. Here, using a gain-of
      function approach, we provide direct and compelling evidence that ELOVL4 is
      required for the synthesis of C28 and C30 saturated fatty acids (VLC-FA) and of
      C28-C38 very long chain polyunsaturated fatty acids (VLC-PUFA), the latter being
      uniquely expressed in retina, sperm, and brain. Rat neonatal cardiomyocytes and a
      human retinal epithelium cell line (ARPE-19) were transduced with recombinant
      adenovirus type 5 carrying mouse Elovl4 and supplemented with 24:0, 20:5n3, or
      22:5n3. The 24:0 was elongated to 28:0 and 30:0; 20:5n3 and 22:5n3 were elongated
      to a series of C28-C38 PUFA. Because retinal degeneration is the only known
      phenotype in STGD3 disease, we propose that reduced VLC-PUFA in the retinas of
      these patients may be the cause of photoreceptor cell death.

PMID- 18728185
TI  - Genetically encoded photoswitching of actin assembly through the Cdc42-WASP
      Arp2/3 complex pathway.
AB  - General methods to engineer genetically encoded, reversible, light-mediated
      control over protein function would be useful in many areas of biomedical
      research and technology. We describe a system that yields such photo-control over
      actin assembly. We fused the Rho family GTPase Cdc42 in its GDP-bound form to the
      photosensory domain of phytochrome B (PhyB) and fused the Cdc42 effector, the
      Wiskott-Aldrich Syndrome Protein (WASP), to the light-dependent PhyB-binding
      domain of phytochrome interacting factor 3 (Pif3). Upon red light illumination,
      the fusion proteins bind each other, activating WASP, and consequently
      stimulating actin assembly by the WASP target, the Arp2/3 complex. Binding and
      WASP activation are reversed by far-red illumination. Our approach, in which the
      biochemical specificity of the nucleotide switch in Cdc42 is overridden by the
      light-dependent PhyB-Pif3 interaction, should be generally applicable to other
      GTPase-effector pairs.

PMID- 18728186
TI  - EPAC and PKA allow cAMP dual control over DNA-PK nuclear translocation.
AB  - We identify a compartmentalized signaling system that identifies a functional
      role for the GTP exchange factor, exchange protein activated by cAMP (EPAC)
      coupled to Rap2 in the nucleus. In this system, cAMP regulates the
      nuclear/cytoplasmic trafficking of DNA-dependent protein kinase (DNA-PK), a
      critical kinase that acts to repair double-stranded breaks (DSBs) in damaged DNA
      and to phosphorylate the cell survival kinase, PKB/Akt. Intersecting regulatory
      inputs for cAMP employ EPAC to transduce positive effects, namely the Rap2
      dependent nuclear exit and activation of DNA-PK, whereas protein kinase A (PKA)
      provides the negative input by antagonizing these actions. We identify this as a
      compartmentalized regulatory system where modulation of cAMP input into the
      stimulatory, EPAC and inhibitory, PKA intersecting arms is provided by spatially
      discrete, cAMP degradation systems. The distribution of DNA-PK between nuclear
      and cytoplasmic compartments can thus potentially be influenced by relative
      inputs of cAMP signaling through the EPAC and PKA pathways. Through this
      signaling system EPAC activation can thereby impact on the Ser-473
      phosphorylation status of PKB/Akt and the repair of etoposide-induced DSBs.

PMID- 18728187
TI  - Primary cilia regulate hippocampal neurogenesis by mediating sonic hedgehog
      signaling.
AB  - Primary cilia are present on mammalian neurons and glia, but their function is
      largely unknown. We generated conditional homozygous mutant mice for a gene we
      termed Stumpy. Mutants lack cilia and have conspicuous abnormalities in
      postnatally developing brain regions, including a hypoplasic hippocampus
      characterized by a primary deficiency in neural stem cells known as astrocyte
      like neural precursors (ALNPs). Previous studies suggested that primary cilia
      mediate sonic hedgehog (Shh) signaling. Here, we find that loss of ALNP cilia
      leads to abrogated Shh activity, increased cell cycle exit, and morphological
      abnormalities in ALNPs. Processing of Gli3, a mediator of Shh signaling, is also
      altered in the absence of cilia. Further, key mediators of the Shh pathway
      localize to ALNP cilia. Thus, selective targeting of Shh machinery to primary
      cilia confers to ALNPs the ability to differentially respond to Shh mitogenic
      signals compared to neighboring cells. Our data suggest these organelles are
      cellular "antennae" critically required to modulate ALNP behavior.

PMID- 18728188
TI  - Immunosuppressive therapy mitigates immunological rejection of human embryonic
      stem cell xenografts.
AB  - Given their self-renewing and pluripotent capabilities, human embryonic stem
      cells (hESCs) are well poised as a cellular source for tissue regeneration
      therapy. However, the host immune response against transplanted hESCs is not well
      characterized. In fact, controversy remains as to whether hESCs have immune
      privileged properties. To address this issue, we used in vivo bioluminescent
      imaging to track the fate of transplanted hESCs stably transduced with a double
      fusion reporter gene consisting of firefly luciferase and enhanced GFP. We show
      that survival after transplant is significantly limited in immunocompetent as
      opposed to immunodeficient mice. Repeated transplantation of hESCs into
      immunocompetent hosts results in accelerated hESC death, suggesting an adaptive
      donor-specific immune response. Our data demonstrate that transplanted hESCs
      trigger robust cellular and humoral immune responses, resulting in intragraft
      infiltration of inflammatory cells and subsequent hESC rejection. Moreover, we
      have found CD4(+) T cells to be an important modulator of hESC immune-mediated
      rejection. Finally, we show that immunosuppressive drug regimens can mitigate the
      anti-hESC immune response and that a regimen of combined tacrolimus and sirolimus
      therapies significantly prolongs survival of hESCs for up to 28 days. Taken
      together, these data suggest that hESCs are immunogenic, trigger both cellular
      and humoral-mediated pathways, and, as a result, are rapidly rejected in
      xenogeneic hosts. This process can be mitigated by a combined immunosuppressive
      regimen as assessed by molecular imaging approaches.

PMID- 18728189
TI  - Mass incarceration can explain population increases in TB and multidrug-resistant
      TB in European and central Asian countries.
AB  - Several microlevel studies have pinpointed prisons as an important site for
      tuberculosis (TB) and multidrug-resistant TB in European and central Asian
      countries. To date, no comparative analyses have examined whether rises in
      incarceration rates can account for puzzling differences in TB trends among
      overall populations. Using longitudinal TB and cross-sectional multidrug
      resistant TB data for 26 eastern European and central Asian countries, we
      examined whether and to what degree increases in incarceration account for
      differences in population TB and multidrug-resistant TB burdens. We find that
      each percentage point increase in incarceration rates relates to an increased TB
      incidence of 0.34% (population attributable risk, 95% C.I.: 0.10-0.58%, P <
      0.01), after controlling for TB infrastructure; HIV prevalence; and several
      surveillance, economic, demographic, and political indicators. Net increases in
      incarceration account for a 20.5% increase in TB incidence or nearly three-fifths
      of the average total increase in TB incidence in the countries studied from 1991
      to 2002. Although the number of prisoners is a significant determinant of
      differences in TB incidence and multidrug-resistant TB prevalence among
      countries, the rate of prison growth is a larger determinant of these outcomes,
      and its effect is exacerbated but not confounded by HIV. Differences in
      incarceration rates are a major determinant of differences in population TB
      outcomes among eastern European and central Asian countries, and treatment
      expansion alone does not appear to resolve the effect of mass incarceration on TB
      incidence.

PMID- 18728190
TI  - Dematerialization: Variety, caution, and persistence.
AB  - Dematerialization, represented by declining consumption per GDP of energy or of
      goods, offers some hope for rising environmental quality with development. The
      declining proportion of income spent on staples as affluence grows, which income
      elasticity <1.0 measures, makes dematerialization widespread. Further, as
      learning improves efficiency of resource use, the intensity of environmental
      impact per production of staples often declines. We observe that combinations of
      low income elasticity for staples and of learning by producers cause a variety of
      dematerializations and declining intensities of impact, from energy use and
      carbon emission to food consumption and fertilizer use, globally and in countries
      ranging from the United States and France to China, India, Brazil, and Indonesia.
      Because dematerialization and intensity of impact are ratios of parameters that
      may be variously defined and are sometimes difficult to estimate, their
      fluctuations must be interpreted cautiously. Nevertheless, substantial declining
      intensity of impact, and especially, dematerialization persisted between 1980 and
      2006.

PMID- 18728191
TI  - NGF and BDNF signaling control amyloidogenic route and Abeta production in
      hippocampal neurons.
AB  - Here, we report that interruption of NGF or BDNF signaling in hippocampal neurons
      rapidly activates the amyloidogenic pathway and causes neuronal apoptotic death.
      These events are associated with an early intracellular accumulation of PS1 N
      terminal catalytic subunits and of APP C-terminal fragments and a progressive
      accumulation of intra- and extracellular Abeta aggregates partly released into
      the culture medium. The released pool of Abeta induces an increase of APP and PS1
      holoprotein levels, creating a feed-forward toxic loop that might also cause the
      death of healthy neurons. These events are mimicked by exogenously added Abeta
      and are prevented by exposure to beta- and gamma-secretase inhibitors and by
      antibodies directed against Abeta peptides. The same cultured neurons deprived of
      serum die, but APP and PS1 overexpression does not occur, Abeta production is
      undetectable, and cell death is not inhibited by anti-Abeta antibodies,
      suggesting that hippocampal amyloidogenesis is not a simple consequence of an
      apoptotic trigger but is due to interruption of neurotrophic signaling.

PMID- 18728192
TI  - The fusing ability of sperm is bestowed by CD9-containing vesicles released from
      eggs in mice.
AB  - Membrane fusion is an essential step in the encounter of two nuclei from sex
      cells-sperm and egg-in fertilization. However, aside from the involvement of two
      molecules, CD9 and Izumo, the mechanism of fusion remains unclear. Here, we show
      that sperm-egg fusion is mediated by vesicles containing CD9 that are released
      from the egg and interact with sperm. We demonstrate that the CD9(-/-) eggs,
      which have a defective sperm-fusing ability, have impaired release of CD9
      containing vesicles. We investigate the fusion-facilitating activity of CD9
      containing vesicles by examining the fusion of sperm to CD9(-/-) eggs with the
      aid of exogenous CD9-containing vesicles. Moreover, we show, by examining the
      fusion of sperm to CD9(-/-) eggs, that hamster eggs have a similar fusing ability
      as mouse eggs. The CD9-containing vesicle release from unfertilized eggs provides
      insight into the mechanism required for fusion with sperm.

PMID- 18728193
TI  - Replica exchange simulations of transient encounter complexes in protein-protein
      association.
AB  - Recent paramagnetic relaxation enhancement (PRE) studies on several weakly
      interacting protein complexes have unequivocally demonstrated the existence of
      transient encounter complexes. Here, we present a computational method to study
      protein-protein binding by creating equilibrium ensembles that include both
      specific and nonspecific protein complexes. In a joint analysis of simulation and
      experiment we explore the physical nature and underlying physicochemical
      characteristics of encounter complexes involving three protein-protein
      interactions of the bacterial phosphotransferase system. Replica exchange Monte
      Carlo simulations using a coarse-grained energy function recover the structures
      of the specific complexes and produce binding affinities in good agreement with
      experiment. Together with the specific complex, a relatively small number of
      distinct nonspecific complexes largely accounts for the measured PRE data. The
      combined relative population of the latter is less than approximately 10%. The
      binding interfaces of the specific and nonspecific complexes differ primarily in
      size but exhibit similar amino acid compositions. We find that the overall funnel
      shaped energy landscape of complex formation is dominated by the specific
      complex, a small number of structured nonspecific complexes, and a diffuse cloud
      of loosely bound complexes connecting the specific and nonspecific binding sites
      with each other and the unbound state. Nonspecific complexes may not only
      accelerate the binding kinetics by enhancing the rate of success of random
      diffusional encounters but also play a role in protein function as alternative
      binding modes.

PMID- 18728194
TI  - Overexpression of Separase induces aneuploidy and mammary tumorigenesis.
AB  - Separase is an endopeptidase that separates sister chromatids by cleaving cohesin
      Rad21 during the metaphase-to-anaphase transition. Conditional expression of
      Separase in tetracycline-inducible diploid FSK3 mouse mammary epithelial cells
      with both p53 WT and mutant (Ser-233-234) alleles of unknown physiological
      significance develops aneuploidy within 5 days of Separase induction in vitro.
      Overexpression of Separase induces premature separation of chromatids, lagging
      chromosomes, and anaphase bridges. In an in vivo mouse mammary transplant model,
      induction of Separase expression in the transplanted FSK3 cells for 3-4 weeks
      results in the formation of aneuploid tumors in the mammary gland. Xenograft
      studies combined with histological and cytogenetic analysis reveal that Separase
      induced tumors are clonal in their genomic complements and have a mesenchymal
      phenotype suggestive of an epithelial-mesenchymal transition. Induction of
      Separase resulted in trisomies for chromosomes 8, 15, and 17; monosomy for
      chromosome 10; and amplification of the distal region of chromosomes 8 and 11.
      Separase protein is found to be significantly overexpressed in human breast
      tumors compared with matched normal tissue. These results collectively suggest
      that Separase is an oncogene, whose overexpression alone in mammary epithelial
      cells is sufficient to induce aneuploidy and tumorigenesis in a p53 mutant
      background.

PMID- 18728195
TI  - Semaphorin 6D regulates the late phase of CD4+ T cell primary immune responses.
AB  - The semaphorin and plexin family of ligand and receptor proteins provides
      important axon guidance cues required for development. Recent studies have
      expanded the role of semaphorins and plexins in the regulation of cardiac,
      circulatory and immune system function. Within the immune system, semaphorins and
      plexins regulate cell-cell interactions through a complex network of receptor and
      ligand pairs. Immune cells at different stages of development often express
      multiple semaphorins and plexins, leading to multivariate interactions, involving
      more than one ligand and receptor within each functional group. Because of this
      complexity, the significance of semaphorin and plexin regulation on individual
      immune cell types has yet to be fully appreciated. In this work, we examined the
      regulation of T cells by semaphorin 6D. Both in vitro and in vivo T cell
      stimulation enhanced semaphorin 6D expression. However, semaphorin 6D was only
      expressed by a majority of T cells during the late phases of activation.
      Consequently, the targeted disruption of semaphorin 6D receptor-ligand
      interactions inhibited T cell proliferation at late but not early phases of
      activation. This proliferation defect was associated with reduced linker of
      activated T cells protein phosphorylation, which may reflect semaphorin 6D
      regulation of c-Abl kinase activity. Semaphorin 6D disruption also inhibited
      expression of CD127, which is required during the multiphase antigen-presenting
      cell and T cell interactions leading to selection of long-lived lymphocytes. This
      work reveals a role for semaphorin 6D as a regulator of the late phase of primary
      immune responses.

PMID- 18728196
TI  - Regulation of the SigH stress response regulon by an essential protein kinase in
      Mycobacterium tuberculosis.
AB  - SigH is a key regulator of an extensive transcriptional network that responds to
      oxidative, nitrosative, and heat stresses in Mycobacterium tuberculosis, and this
      sigma factor is required for virulence in animal models of infection. SigH is
      negatively regulated by RshA, its cognate anti-sigma factor, which functions as a
      stress sensor and redox switch. While RshA provides a direct mechanism for
      sensing stress and activating transcription, bacteria use several types of signal
      transduction systems to sense the external environment. M. tuberculosis encodes
      several serine-threonine protein kinase signaling molecules, 2 of which, PknA and
      PknB, are essential and have been shown to regulate cell morphology and cell wall
      synthesis. In this work, we demonstrate that SigH and RshA are phosphorylated in
      vitro and in vivo by PknB. We show that phosphorylation of RshA, but not SigH,
      interferes with the interaction of these 2 proteins in vitro. Consistent with
      this finding, negative regulation of SigH activity by RshA in vivo is partially
      relieved in strains in which pknB is over-expressed, resulting in increased
      resistance to oxidative stress. These findings demonstrate an interaction between
      the signaling pathways mediated by PknB and the stress response regulon
      controlled by SigH. The intersection of these apparently discrete regulatory
      systems provides a mechanism by which limited activation of the SigH-dependent
      stress response in M. tuberculosis can be achieved. Coordination of the PknB and
      SigH regulatory pathways through phosphorylation of RshA may lead to adaptive
      responses that are important in the pathogenesis of M. tuberculosis infection.

PMID- 18728197
TI  - Inferior parietal lobule supports decision making under uncertainty in humans.
AB  - The optimal responses for many decisions faced by humans are ill defined, yet we
      are able to choose well by associating choices with outcomes, and employing this
      information in decision making. Previous studies suggest that the parietal cortex
      is involved in "uncertain" decision making, yet uncertainty is confounded with
      increased difficulty and attention. Here we aim to dissociate the role of
      parietal cortex in decision making and attention. Using functional magnetic
      resonance imaging we measured brain activity while participants played a
      "matching-pennies" game. We found that the inferior parietal lobule is involved
      in decision making under uncertainty, showing higher activity when the decision
      was uncertain rather than certain and when humans were given trial-by-trial
      feedback on choice outcomes than when they were not. Crucially, increasing
      attentional load with secondary tasks reduced inferior parietal activity when
      decisions were made under uncertainty, suggesting that general attention does not
      drive its activation. This pattern was consistent for visual or auditory
      feedback, and for direct (symbols representing wins and losses) or indirect (only
      the opponent's choices were shown) feedback. It contrasted with results from
      medial superior frontal gyrus, which was driven primarily by increased
      attentional load. We suggest that decision making under uncertainty is
      dissociable from general attention in the brain.

PMID- 18728198
TI  - COPD, diagrams and traditions: time to move on?

PMID- 18728199
TI  - What evidence could validate the definition of COPD?

PMID- 18728200
TI  - Recent advances in exacerbations of asthma.

PMID- 18728201
TI  - Proportional classifications of COPD phenotypes.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) encompasses a group of
      disorders characterised by the presence of incompletely reversible airflow
      obstruction with overlapping subsets of different phenotypes including chronic
      bronchitis, emphysema or asthma. The aim of this study was to determine the
      proportion of adult subjects aged >50 years within each phenotypic subgroup of
      COPD, defined as a post-bronchodilator ratio of forced expiratory volume in 1
      s/forced vital capacity (FEV(1)/FVC) <0.7, in accordance with current
      international guidelines. METHODS: Adults aged >50 years derived from a random
      population-based survey undertook detailed questionnaires, pulmonary function
      tests and chest CT scans. The proportion of subjects in each of 16 distinct
      phenotypes was determined based on combinations of chronic bronchitis, emphysema
      and asthma, with and without incompletely reversible airflow obstruction defined
      by a post-bronchodilator FEV(1)/FVC ratio of 0.7. RESULTS: A total of 469
      subjects completed the investigative modules, 96 of whom (20.5%) had COPD.
      Diagrams were constructed to demonstrate the relative proportions of the
      phenotypic subgroups in subjects with and without COPD. 18/96 subjects with COPD
      (19%) had the classical phenotypes of chronic bronchitis and/or emphysema but no
      asthma; asthma was the predominant COPD phenotype, being present in 53/96 (55%).
      When COPD was defined as a post-bronchodilator FEV(1)/FVC less than the lower
      limit of normal, there were one-third fewer subjects with COPD and a smaller
      proportion without a defined emphysema, chronic bronchitis or asthma phenotype.
      CONCLUSION: This study provides proportional classifications of the phenotypic
      subgroups of COPD which can be used as the basis for further research into the
      pathogenesis and treatment of this heterogeneous disorder.

PMID- 18728204
TI  - Acute respiratory distress in a patient using non-invasive ventilation.

PMID- 18728206
TI  - Patient adherence in COPD.
AB  - Patient adherence to treatment in chronic obstructive pulmonary disease (COPD) is
      essential to optimise disease management. As with other chronic diseases, poor
      adherence is common and results in increased rates of morbidity, healthcare
      expenditures, hospitalisations and possibly mortality, as well as unnecessary
      escalation of therapy and reduced quality of life. Examples include overuse,
      underuse, and alteration of schedule and doses of medication, continued smoking
      and lack of exercise. Adherence is affected by patients' perception of their
      disease, type of treatment or medication, the quality of patient provider
      communication and the social environment. Patients are more likely to adhere to
      treatment when they believe it will improve disease management or control, or
      anticipate serious consequences related to non-adherence. Providers play a
      critical role in helping patients understand the nature of the disease, potential
      benefits of treatment, addressing concerns regarding potential adverse effects
      and events, and encouraging patients to develop self-management skills. For
      clinicians, it is important to explore patients' beliefs and concerns about the
      safety and benefits of the treatment, as many patients harbour unspoken fears.
      Complex regimens and polytherapy also contribute to suboptimal adherence. This
      review addresses adherence related issues in COPD, assesses current efforts to
      improve adherence and highlights opportunities to improve adherence for both
      providers and patients.

PMID- 18728207
TI  - Transmission of Pseudomonas aeruginosa epidemic strain from a patient with cystic
      fibrosis to a pet cat.
AB  - Chronic infection with Pseudomonas aeruginosa is common in cystic fibrosis (CF)
      and certain strains are more transmissible and virulent than others. Of these,
      the Liverpool Epidemic Strain (LES) is highly transmissible and cross infection
      has been reported between patients with CF and healthy non-CF relatives. However,
      the risk of transmission from humans to animals is unknown. The first report of
      interspecies transmission of the LES strain of P aeruginosa from an adult patient
      with CF to a pet cat is described. This development further complicates the issue
      of infection control policies required to prevent the spread of this organism.

PMID- 18728208
TI  - Strategies to screen for adrenal suppression in children with asthma: there is no
      consensus among UK centres.

PMID- 18728209
TI  - International registry for idiopathic pulmonary fibrosis.

PMID- 18728210
TI  - Predicting risk of asthma in wheezing infants.

PMID- 18728211
TI  - Serum free DNA and COX-2 mRNA expression in peripheral blood for lung cancer
      detection.

PMID- 18728214
TI  - Intercostal ancient schwannoma mimicking an apical lung tumour.

PMID- 18728215
TI  - Interpreting results of clinical trials: a conceptual framework.

PMID- 18728216
TI  - Inhibition of a eukaryotic initiation factor (eIF2Bdelta/F11A3.2) during
      adulthood extends lifespan in Caenorhabditis elegans.
AB  - The critical role of protein synthesis in regulating lifespan has been evidenced.
      This study shows that adult-onset RNAi inactivation of eukaryotic initiation
      factor 2Bdelta (eIF2Bdelta/F11A3.2), a subunit of eIF2B, extends the mean
      lifespan of Caenorhabditis elegans. eIF2B is a GDP-GTP exchange factor for eIF2-
      a rate-limiting factor for protein synthesis initiation. (35)S-methionine
      incorporation assay showed that global protein synthesis is reduced by
      eIF2Bdelta/F11A3.2 RNAi. Inhibition of eIF2Bdelta/F11A3.2 during adulthood
      conferred thermal and oxidative stress resistance and reduced the fecundity and
      fat storage, suggesting the possible trade-offs of resources between reproduction
      and somatic maintenance. Lifespan extension by adult-onset eIF2Bdelta/F11A3.2
      RNAi is suppressed in FOXO transcription factor daf-16 deletion mutants. Adult
      onset eIF2Bdelta/F11A3.2 RNAi increases the expression of stress-resistant genes,
      including hsp-16.2, hsp-70, hsp90, and sod-3, some of which are reported to be
      targets of DAF-16. Adult-onset eIF2Bdelta/F11A3.2 RNAi in daf-16 mutants reduced
      fecundity, but did not extend lifespan. Furthermore, adult-onset
      eIF2Bdelta/F11A3.2 RNAi did not extend the lifespan of germline-defective glp-4
      organisms. Thus, it is possible that eIF2Bdelta/F11A3.2 RNAi during adulthood
      prolongs lifespan via daf-16, which induces stress resistance in organisms. This
      might be the mechanism, at least in part, for trade-offs of resources between
      reproduction and somatic maintenance.

PMID- 18728217
TI  - Ischemic preconditioning-induced cardioprotection is lost in mice with
      immunoproteasome subunit low molecular mass polypeptide-2 deficiency.
AB  - The ubiquitin-proteasome system plays an important role in many cellular
      processes through degradation of specific proteins. Low molecular mass
      polypeptide 2 (LMP-2 or beta(1i)) is one important subunit of the
      immunoproteasome. Ischemic preconditioning (IPC) activates cell signaling
      pathways and generates cardioprotection but has not been linked to LMP-2 function
      previously. LMP-2 knockout mice (C57BL6 background) and wild-type C57BL6 mice
      were subjected to 30 min of ischemia (I-30) and 120 min of reperfusion (R-120)
      with or without preceding IPC (10 min of infusion and 5 min of reperfusion). IPC
      significantly increased left ventricular developed pressure and decreased infarct
      size in wild-type mice, but this protective effect of IPC was lost in LMP-2
      knockout mice. IPC-mediated degradation of phosphatase and tensin homologue
      deleted on chromosome 10 (PTEN) and activation of the downstream protein kinase
      Akt were impaired in LMP-2 knockout hearts. The impairment of PTEN degradation
      was associated with defective immunoproteasomes and decreased proteolytic
      activities. When LMP-2 knockout mice were pretreated with the PTEN inhibitor
      bpV(HOpic), cardiac function was significantly improved, and myocardial infarct
      size was significantly reduced after I-30/R-120. In conclusion, LMP-2 is required
      for normal proteasomal function and IPC induction in the heart. Its action may be
      related to PTEN protein degradation.

PMID- 18728218
TI  - Effect of calpain and proteasome inhibition on Ca2+-dependent proteolysis and
      muscle histopathology in the mdx mouse.
AB  - Dystrophin deficiency is the underlying molecular cause of progressive muscle
      weakness observed in Duchenne muscular dystrophy (DMD). Loss of functional
      dystrophin leads to elevated levels of intracellular Ca(2+), a key step in the
      cellular pathology of DMD. The cysteine protease calpain is activated in
      dystrophin-deficient muscle, and its inhibition is regarded as a potential
      therapeutic approach. In addition, previous work has shown that the ubiquitin
      proteasome system also contributes to muscle protein breakdown in dystrophic
      muscle and, therefore, also qualifies as a potential target for therapeutic
      intervention in DMD. The relative contribution of calpain- and proteasome
      mediated proteolysis induced by increased Ca(2+) levels was characterized in
      cultured muscle cells and revealed initial Ca(2+) influx-dependent calpain
      activity and subsequent Ca(2+)-independent activity of the ubiquitin-proteasome
      system. We then set out to optimize novel small-molecule inhibitors that inhibit
      both calpain as well as the 20S proteasome in a cellular system with impaired
      Ca(2+) homeostasis. On administration of such inhibitors to mdx mice,
      quantitative histological parameters improved significantly, in particular with
      compounds strongly inhibiting the 20S proteasome. To investigate the role of
      calpain inhibition without interfering with the ubiquitin-proteasome system, we
      crossed mdx mice with transgenic mice, overexpressing the endogenous calpain
      inhibitor calpastatin. Although our data show that proteolysis by calpain is
      strongly inhibited in the transgenic mdx mouse, this calpain inhibition did not
      ameliorate muscle histology. Our results indicate that inhibition of the
      proteasome rather than calpain is required for histological improvement of
      dystrophin-deficient muscle. In conclusion, we have identified novel proteasome
      inhibitors that qualify as potential candidates for pharmacological intervention
      in muscular dystrophy.

PMID- 18728219
TI  - Relationship between AMPK and the transcriptional balance of clock-related genes
      in skeletal muscle.
AB  - Circadian clocks coordinate physiological, behavioral, and biochemical events
      with predictable daily environmental changes by a self-sustained transcriptional
      feedback loop. CLOCK and ARNTL are transcriptional activators that regulate Per
      and Cry gene expression. PER and CRY inhibit their own transcription, and their
      turnover allows this cycle to restart. The transcription factors BHLHB2 and
      BHLHB3 repress Per activation, whereas orphan nuclear receptors of the NR1D and
      ROR families control Arntl expression. Here we show the AMP-activated protein
      kinase (AMPK)gamma(3) subunit is involved in the regulation of peripheral
      circadian clock function. AMPKgamma3 knockout (Prkag3(-/-)) mice or wild-type
      littermates were injected with saline or an AMPK activator, 5-amino-4-imidazole
      carboxamide riboside (AICAR), and white glycolytic gastrocnemius muscle was
      removed for gene expression analysis. Genes involved in the regulation of
      circadian rhythms (Cry2, Nr1d1, and Bhlhb2) were differentially regulated in
      response to AICAR in wild-type mice but remained unaltered in Prkag3(-/-) mice.
      Basal expression of Per1 was higher in Prkag3(-/-) mice compared with wild-type
      mice. Distinct diurnal changes in the respiratory exchange ratio (RER) between
      the light and dark phase of the day were observed in wild-type mice but not
      Prkag3(-/-) mice. In summary, the expression profile of clock-related genes in
      skeletal muscle in response to AICAR, as well as the diurnal shift in energy
      utilization, is impaired in AMPKgamma(3) subunit knockout mice. Our results
      indicate AMPK heterotrimeric complexes containing the AMPKgamma(3) subunit may
      play a specific role in linking circadian oscillators and energy metabolism in
      skeletal muscle.

PMID- 18728220
TI  - Regulation of Akt signaling by O-GlcNAc in euglycemia.
AB  - The hexosamine biosynthesis pathway (HBP) regulates the posttranslational
      modification of nuclear and cytoplasmic protein by O-linked N-acetylglucosamine
      (O-GlcNAc). Numerous studies have demonstrated that, in hyperglycemic conditions,
      excessive glucose flux through this pathway contributes to the development of
      insulin resistance. The role of the HBP in euglycemia, however, remains largely
      unknown. Here we investigated the effect of O-GlcNAc on hepatic Akt signaling at
      physiological concentrations of glucose. In HepG2 cells cultured in 5 mM glucose,
      removal of O-GlcNAc by adenoviral-mediated overexpression of O-GlcNAcase
      increased Akt activity and phosphorylation. We also observed that Akt was
      recognized by succinylated wheat germ agglutinin (sWGA), which specifically binds
      O-GlcNAc. Overexpression of O-GlcNAcase in HepG2 cells reduced the levels of Akt
      in sWGA precipitates. The increased Akt activity was accompanied by increased
      phosphorylation of Akt substrates and reduced mRNA for glucose-6-phosphatase and
      phosphoenolpyruvate carboxykinase (PEPCK). The increased Akt activity was not a
      result of activation of its upstream activator phosphoinositide 3-kinase (PI 3
      kinase). Further demonstrating Akt regulation by O-GlcNAc, we found that
      overexpression of O-GlcNAcase in the livers of euglycemic mice also significantly
      increased Akt activity, resulting in increased phosphorylation of downstream
      targets and decreased mRNA for glucose-6-phosphatase. Together, these data
      suggest that O-GlcNAc regulates Akt signaling in hepatic models under euglycemic
      conditions.

PMID- 18728222
TI  - Phosphorylation of IRS proteins, insulin action, and insulin resistance.
AB  - Insulin signaling at target tissues is essential for growth and development and
      for normal homeostasis of glucose, fat, and protein metabolism. Control over this
      process is therefore tightly regulated. It can be achieved by a negative feedback
      control mechanism whereby downstream components inhibit upstream elements along
      the insulin-signaling pathway (autoregulation) or by signals from apparently
      unrelated pathways that inhibit insulin signaling thus leading to insulin
      resistance. Phosphorylation of insulin receptor substrate (IRS) proteins on
      serine residues has emerged as a key step in these control processes under both
      physiological and pathological conditions. The list of IRS kinases implicated in
      the development of insulin resistance is growing rapidly, concomitant with the
      list of potential Ser/Thr phosphorylation sites in IRS proteins. Here, we review
      a range of conditions that activate IRS kinases to phosphorylate IRS proteins on
      "hot spot" domains. The flexibility vs. specificity features of this reaction is
      discussed and its characteristic as an "array" phosphorylation is suggested.
      Finally, its implications on insulin signaling, insulin resistance and type 2
      diabetes, an emerging epidemic of the 21st century are outlined.

PMID- 18728221
TI  - Metabolic cycling in control of glucose-stimulated insulin secretion.
AB  - Glucose-stimulated insulin secretion (GSIS) is central to normal control of
      metabolic fuel homeostasis, and its impairment is a key element of beta-cell
      failure in type 2 diabetes. Glucose exerts its effects on insulin secretion via
      its metabolism in beta-cells to generate stimulus/secretion coupling factors,
      including a rise in the ATP/ADP ratio, which serves to suppress ATP-sensitive
      K(+) (K(ATP)) channels and activate voltage-gated Ca(2+) channels, leading to
      stimulation of insulin granule exocytosis. Whereas this K(ATP) channel-dependent
      mechanism of GSIS has been broadly accepted for more than 30 years, it has become
      increasingly apparent that it does not fully describe the effects of glucose on
      insulin secretion. More recent studies have demonstrated an important role for
      cyclic pathways of pyruvate metabolism in control of insulin secretion. Three
      cycles occur in islet beta-cells: the pyruvate/malate, pyruvate/citrate, and
      pyruvate/isocitrate cycles. This review discusses recent work on the role of each
      of these pathways in control of insulin secretion and builds a case for the
      particular relevance of byproducts of the pyruvate/isocitrate cycle, NADPH and
      alpha-ketoglutarate, in control of GSIS.

PMID- 18728223
TI  - Estrogen directly modulates circadian rhythms of PER2 expression in the uterus.
AB  - Fluctuations in circulating estrogen and progesterone levels associated with the
      estrous cycle alter circadian rhythms of physiology and behavior in female
      rodents. Endogenously applied estrogen shortens the period of the locomotor
      activity rhythm in rodents. We recently found that estrogen implants affect
      Period (Per) gene expression in the suprachiasmatic nucleus (SCN; central clock)
      and uterus of rats in vivo. To explore whether estrogen directly influences the
      circadian clock in the SCN and/or tissues of the reproductive system, we examined
      the effects of 17beta-estradiol (E(2)) on PER2::LUCIFERASE (PER2::LUC) expression
      in tissue explant cultures from ovariectomized PER2::LUC knockin mice. E(2)
      applied to explanted cultures shortened the period of rhythmic PER2::LUC
      expression in the uterus but did not change the period of PER2::LUC expression in
      the SCN. Raloxifene, a selective estrogen receptor modulator and known E(2)
      antagonist in uterine tissues, attenuated the effect of E(2) on the period of the
      PER2::LUC rhythm in the uterus. These data indicate that estrogen directly
      affects the timing of the molecular clock in the uterus via an estrogen receptor
      mediated response.

PMID- 18728225
TI  - Pharmacological characterization of a small molecule inhibitor of c-Jun kinase.
AB  - c-Jun NH(2)-terminal kinase (JNK) plays an important role in insulin resistance;
      however, identification of pharmacologically potent and selective small molecule
      JNK inhibitors has been limited. Compound A has a cell IC(50) of 102 nM and is at
      least 100-fold selective against related kinases and 27-fold selective against
      glycogen synthase kinase-3beta and cyclin-dependent kinase-2. In C57BL/6 mice,
      compound A reduced LPS-mediated increases in both plasma cytokine levels and
      phosphorylated c-Jun in adipose tissue. Treatment of mice fed a high-fat diet
      with compound A for 3 wk resulted in a 13.1 +/- 1% decrease in body weight and a
      9.3 +/- 1.5% decrease in body fat, compared with a 6.6 +/- 2.1% increase in body
      weight and a 6.7 +/- 2.1% increase in body fat in vehicle-treated mice. Mice pair
      fed to those that received compound A exhibited a body weight decrease of 7 +/-
      1% and a decrease in body fat of 1.6 +/- 1.3%, suggesting that reductions in food
      intake could not account solely for the reductions in adiposity observed.
      Compound A dosed at 30 mg/kg for 13 days in high-fat fed mice resulted in a
      significant decrease in phosphorylated c-Jun in adipose tissue accompanied by a
      decrease in weight and reductions in glucose and triglycerides and increases in
      insulin sensitivity to levels comparable with those in lean control mice. The
      ability of compound A to reduce the insulin-stimulated phosphorylation of insulin
      receptor substrate-1 (IRS-1) von Ser307 and partially reverse the free fatty acid
      inhibition of glucose uptake in 3T3L1 adipocytes, suggests that enhancement of
      insulin signaling in addition to weight loss may contribute to the effects of
      compound A on insulin sensitization in vivo. Pharmacological inhibition of JNK
      using compound A may therefore offer an effective therapy for type 2 diabetes
      mediated at least in part via weight reduction.

PMID- 18728224
TI  - Enhanced angiogenesis in obesity and in response to PPARgamma activators through
      adipocyte VEGF and ANGPTL4 production.
AB  - PPARgamma activators such as rosiglitazone (RSG) stimulate adipocyte
      differentiation and increase subcutaneous adipose tissue mass. However, in
      addition to preadipocyte differentiation, adipose tissue expansion requires
      neovascularization to support increased adipocyte numbers. Paradoxically,
      endothelial cell growth and differentiation is potently inhibited by RSG in
      vitro, raising the question of how this drug can induce an increase in adipose
      tissue mass while inhibiting angiogenesis. We find that adipose tissue from mice
      treated with RSG have increased capillary density. To determine whether adipose
      tissue angiogenesis was stimulated by RSG, we developed a novel assay to study
      angiogenic sprout formation ex vivo. Angiogenic sprout formation from equally
      sized adipose tissue fragments, but not from aorta rings, was greatly increased
      by obesity and by TZD treatment in vivo. To define the mechanism involved in RSG
      stimulated angiogenesis in adipose tissue, the expression of proangiogenic
      factors by adipocytes was examined. Expression of VEGFA and VEGFB, as well as of
      the angiopoietin-like factor-4 (ANGPTL4), was stimulated by in vivo treatment
      with RSG. To define the potential role of these factors, we analyzed their
      effects on endothelial cell growth and differentiation in vitro. We found that
      ANGPTL4 stimulates endothelial cell growth and tubule formation, albeit more
      weakly than VEGF. However, ANGPTL4 mitigates the growth inhibitory actions of RSG
      on endothelial cells in the presence or absence of VEGF. Thus, the interplay
      between VEGF and ANGPTL4 could lead to a net expansion of the adipose tissue
      capillary network, required for adipose tissue growth, in response to PPARgamma
      activators.

PMID- 18728226
TI  - Genomic expression analysis of rat chromosome 4 for skeletal traits at femoral
      neck.
AB  - Hip fracture is the most devastating osteoporotic fracture type with significant
      morbidity and mortality. Several studies in humans and animal models identified
      chromosomal regions linked to hip size and bone mass. Previously, we identified
      that the region of 4q21-q41 on rat chromosome (Chr) 4 harbors multiple femoral
      neck quantitative trait loci (QTLs) in inbred Fischer 344 (F344) and Lewis (LEW)
      rats. The purpose of this study is to identify the candidate genes for femoral
      neck structure and density by correlating gene expression in the proximal femur
      with the femoral neck phenotypes linked to the QTLs on Chr 4. RNA was extracted
      from proximal femora of 4-wk-old rats from F344 and LEW strains, and two other
      strains, Copenhagen 2331 and Dark Agouti, were used as a negative control.
      Microarray analysis was performed using Affymetrix Rat Genome 230 2.0 arrays. A
      total of 99 genes in the 4q21-q41 region were differentially expressed (P < 0.05)
      among all strains of rats with a false discovery rate <10%. These 99 genes were
      then ranked based on the strength of correlation between femoral neck phenotypes
      measured in F2 animals, homozygous for a particular strain's allele at the Chr 4
      QTL and the expression level of the gene in that strain. A total of 18 candidate
      genes were strongly correlated (r(2) > 0.50) with femoral neck width and
      prioritized for further analysis. Quantitative PCR analysis confirmed 14 of 18 of
      the candidate genes. Ingenuity pathway analysis revealed several direct or
      indirect relationships among the candidate genes related to angiogenesis (VEGF),
      bone growth (FGF2), bone formation (IGF2 and IGF2BP3), and resorption (TNF). This
      study provides a shortened list of genetic determinants of skeletal traits at the
      hip and may lead to novel approaches for prevention and treatment of hip
      fracture.

PMID- 18728227
TI  - Effect of starvation on transcriptomes of brain and liver in adult female
      zebrafish (Danio rerio).
AB  - We used microarray and quantitative real-time PCR (qRT-PCR) analyses in adult
      female zebrafish (Danio rerio) to identify metabolic pathways regulated by
      starvation in the liver and brain. The transcriptome of whole zebrafish brain
      showed little response to 21 days of starvation. Only agouti-related protein 1
      (agrp1) significantly responded, with increased expression in brains of starved
      fish. In contrast, a 21-day period of starvation significantly downregulated 466
      and upregulated 108 transcripts in the liver, indicating an overall decrease in
      metabolic activity, reduced lipid metabolism, protein biosynthesis, proteolysis,
      and cellular respiration, and increased gluconeogenesis. Starvation also
      regulated expression of many components of the unfolded protein response, the
      first such report in a species other than yeast (Saccharomyces cerevisiae) and
      mice (Mus musculus). The response of the zebrafish hepatic transcriptome to
      starvation was strikingly similar to that of rainbow trout (Oncorhynchus mykiss)
      and less similar to mouse, while the response of common carp (Cyprinus carpio)
      differed considerably from the other three species.

PMID- 18728228
TI  - Response of the adipose tissue transcriptome to dihydrotestosterone in mice.
AB  - Androgens have been postulated to be important modulators of adipose tissue
      metabolism and fat cell function. In the present study, we investigated the
      response of male and female mice retroperitoneal adipose tissue to the
      nonaromatizable androgen dihydrotestosterone (DHT). Adipose tissue samples were
      obtained in gonadectomized animals treated with vehicle (control group), or
      injected with 0.1 mg DHT 1, 3, 6, 12, 18, and 24 h prior to necropsy. Fourteen
      animals were pooled at each time point (total 196 animals). Transcripts that were
      significantly modulated were considered as androgen-responsive genes.
      Quantitative real-time RT-PCR was used to confirm results from the microarray
      analysis in a subset of 46 probe sets in male mice and 98 probe sets in female
      mice. Considering peak time vs. control, we confirmed 74.0 and 63.3% of the
      modulated genes by PCR in males and females, respectively. Four genes were
      significantly stimulated in a similar manner by DHT in both sexes, namely
      metallothionein 1, growth arrest and DNA-damage-inducible 45 gamma, cyclin
      dependent kinase inhibitor 1A, and fk506-binding protein 5. All these genes
      appear to be involved in the regulation of adipocyte
      differentiation/proliferation and adipogenesis. In conclusion, this study, which
      evaluated the acute transcriptome response of adipose tissue to DHT in male and
      female mice, suggests that DHT consistently modulates genes involved in the
      regulation of adipogenesis in retroperitoneal adipose tissue of both male and
      female animals.

PMID- 18728229
TI  - Beta-cell proliferation, but not neogenesis, following 60% partial pancreatectomy
      is impaired in the absence of FoxM1.
AB  - OBJECTIVE: This study was designed to determine whether the transcription factor
      FoxM1 was required for regeneration of beta-cell mass via proliferation and/or
      neogenesis in the adult after 60% partial pancreatectomy (PPx). RESEARCH DESIGN
      AND METHODS: Adult mice with a pancreas-wide deletion of Foxm1
      (Foxm1(flox/flox);Pdx1-Cre [FoxM1(Deltapanc)]) and their control littermates
      (Foxm1(flox/flox)) were subjected to PPx or a sham operation, after which islet
      expression of Foxm1 and several target genes, beta-cell mass, proliferation, beta
      cell size, islet size, islet density, and neurogenin-3 expression were analyzed.
      RESULTS: In control mice, PPx stimulated beta-cell proliferation and neogenesis
      and upregulated Foxm1 and several of its known targets (Plk1, Cenp-a,
      Birc5/Survivin, and Ccnb1) in islets. Within 1 week post-PPx, control mice
      underwent significant regeneration of beta-cell mass, and average islet size
      within the regenerating lobe was similar to that after a sham operation. However,
      FoxM1(Deltapanc) mice exhibited specific impairments in beta-cell mass
      regeneration and islet growth after PPx, with reduced proliferation of alpha- and
      beta-cells but no impairments in acinar or ductal cell proliferation.
      Interestingly, FoxM1 was not required for proliferation of beta-cells within
      small endocrine cell clusters located in the regenerating portion of the pancreas
      but was specifically required for proliferation of beta-cells within larger
      islets. Additionally, FoxM1 was not required for beta-cell neogenesis following
      PPx. CONCLUSIONS: Our results indicate that FoxM1 is partially required for
      increased beta-cell proliferation, but not beta-cell neogenesis, stimulated by
      PPx. Furthermore, FoxM1 seems to be dispensable for proliferation of beta-cells
      following neogenesis but is required for proliferation of preexisting beta-cells.

PMID- 18728230
TI  - Decreased cardiac glutathione peroxidase levels and enhanced mandibular apoptosis
      in malformed embryos of diabetic rats.
AB  - OBJECTIVE: To characterize normal and malformed embryos within the same litters
      from control and diabetic rats for expression of genes related to metabolism of
      reactive oxygen species (ROS) or glucose as well as developmental genes. RESEARCH
      DESIGN AND METHODS: Embryos from nondiabetic and streptozotocin-induced diabetic
      rats were collected on gestational day 11 and evaluated for gene expression (PCR)
      and distribution of activated caspase-3 and glutathione peroxidase (Gpx)-1 by
      immunohistochemistry. RESULTS: Maternal diabetes (MD group) caused growth
      retardation and an increased malformation rate in the embryos of MD group rats
      compared with those of controls (N group). We found decreased gene expression of
      Gpx-1 and increased expression of vascular endothelial growth factor-A (Vegf-A)
      in malformed embryos of diabetic rats (MDm group) compared with nonmalformed
      littermates (MDn group). Alterations of messenger RNA levels of other genes were
      similar in MDm and MDn embryos. Thus, expression of copper zinc superoxide
      dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), and sonic hedgehog
      homolog (Shh) were decreased, and bone morphogenetic protein-4 (Bmp-4) was
      increased, in the MD embryos compared with the N embryos. In MDm embryos, we
      detected increased activated caspase-3 immunostaining in the first visceral arch
      and cardiac area and decreased Gpx-1 immunostaining in the cardiac tissue; both
      findings differed from the caspase/Gpx-1 immunostaining of the MDn and N embryos.
      CONCLUSIONS: Maternal diabetes causes growth retardation, congenital
      malformations, and decreased general antioxidative gene expression in the embryo.
      In particular, enhanced apoptosis of the first visceral arch and heart, together
      with decreased cardiac Gpx-1 levels, may compromise the mandible and heart and
      thus cause an increased risk of developing congenital malformation.

PMID- 18728231
TI  - Population-specific risk of type 2 diabetes conferred by HNF4A P2 promoter
      variants: a lesson for replication studies.
AB  - OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the P2 promoter region of
      HNF4A were originally shown to be associated with predisposition for type 2
      diabetes in Finnish, Ashkenazi, and, more recently, Scandinavian populations, but
      they generated conflicting results in additional populations. We aimed to
      investigate whether data from a large-scale mapping approach would replicate this
      association in novel Ashkenazi samples and in U.K. populations and whether these
      data would allow us to refine the association signal. RESEARCH DESIGN AND
      METHODS: Using a dense linkage disequilibrium map of 20q, we selected SNPs from a
      10-Mb interval centered on HNF4A. In a staged approach, we first typed 4,608 SNPs
      in case-control populations from four U.K. populations and an Ashkenazi
      population (n = 2,516). In phase 2, a subset of 763 SNPs was genotyped in 2,513
      additional samples from the same populations. RESULTS: Combined analysis of both
      phases demonstrated association between HNF4A P2 SNPs (rs1884613 and rs2144908)
      and type 2 diabetes in the Ashkenazim (n = 991; P < 1.6 x 10(-6)). Importantly,
      these associations are significant in a subset of Ashkenazi samples (n = 531) not
      previously tested for association with P2 SNPs (odds ratio [OR] approximately
      1.7; P < 0.002), thus providing replication within the Ashkenazim. In the U.K.
      populations, this association was not significant (n = 4,022; P > 0.5), and the
      estimate for the OR was much smaller (OR 1.04; [95%CI 0.91-1.19]). CONCLUSIONS:
      These data indicate that the risk conferred by HNF4A P2 is significantly
      different between U.K. and Ashkenazi populations (P < 0.00007), suggesting that
      the underlying causal variant remains unidentified. Interactions with other
      genetic or environmental factors may also contribute to this difference in risk
      between populations.

PMID- 18728232
TI  - Forkhead transcription factors (FoxOs) promote apoptosis of insulin-resistant
      macrophages during cholesterol-induced endoplasmic reticulum stress.
AB  - OBJECTIVE: Endoplasmic reticulum stress increases macrophage apoptosis,
      contributing to the complications of atherosclerosis. Insulin-resistant
      macrophages are more susceptible to endoplasmic reticulum stress-associated
      apoptosis probably contributing to macrophage death and necrotic core formation
      in atherosclerotic plaques in type 2 diabetes. However, the molecular mechanisms
      of increased apoptosis in insulin-resistant macrophages remain unclear. RESEARCH
      DESIGN AND METHODS: The studies were performed in insulin-resistant macrophages
      isolated from insulin receptor knockout or ob/ob mice. Gain- or loss-of-function
      approaches were used to evaluate the roles of forkhead transcription factors
      (FoxOs) in endoplasmic reticulum stress-associated macrophage apoptosis. RESULTS:
      Insulin-resistant macrophages showed attenuated Akt activation and increased
      nuclear localization of FoxO1 during endoplasmic reticulum stress induced by free
      cholesterol loading. Overexpression of active FoxO1 or FoxO3 failed to induce
      apoptosis in unchallenged macrophages but exacerbated apoptosis in macrophages
      with an active endoplasmic reticulum stress response. Conversely, macrophages
      with genetic knockouts of FoxO1, -3, and -4 were resistant to apoptosis in
      response to endoplasmic reticulum stress. FoxO1 was shown by chromatin
      immunoprecipitation and promoter expression analysis to induce inhibitor of
      kappaBepsilon gene expression and thereby to attenuate the increase of nuclear
      p65 and nuclear factor-kappaB activity during endoplasmic reticulum stress, with
      proapoptotic and anti-inflammatory consequences. CONCLUSIONS: Decreased Akt and
      increased FoxO transcription factor activity during the endoplasmic reticulum
      stress response leads to increased apoptosis of insulin-resistant macrophages.
      FoxOs may have a dual cellular function, resulting in either proapoptotic or anti
      inflammatory effects in an endoplasmic reticulum stress-modulated manner. In the
      complex plaque milieu, the ultimate effect is likely to be an increase in
      macrophage apoptosis, plaque inflammation, and destabilization.

PMID- 18728233
TI  - Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic
      polyneuropathy in rats.
AB  - OBJECTIVE: Mesenchymal stem cells (MSCs) have been reported to secrete various
      cytokines that exhibit angiogenic and neurosupportive effects. This study was
      conducted to investigate the effects of MSC transplantation on diabetic
      polyneuropathy (DPN) in rats. RESEARCH DESIGN AND METHODS: MSCs were isolated
      from bone marrow of adult rats and transplanted into hind limb skeletal muscles
      of rats with an 8-week duration of streptozotocin (STZ)-induced diabetes or age
      matched normal rats by unilateral intramuscular injection. Four weeks after
      transplantation, vascular endothelial growth factor (VEGF) and basic fibroblast
      growth factor (bFGF) productions in transplanted sites, current perception
      threshold, nerve conduction velocity (NCV), sciatic nerve blood flow (SNBF),
      capillary number-to-muscle fiber ratio in soleus muscles, and sural nerve
      morphometry were evaluated. RESULTS: VEGF and bFGF mRNA expression were
      significantly increased in MSC-injected thigh muscles of STZ-induced diabetic
      rats. Furthermore, colocalization of MSCs with VEGF and bFGF in the transplanted
      sites was confirmed. STZ-induced diabetic rats showed hypoalgesia, delayed NCV,
      decreased SNBF, and decreased capillary number-to-muscle fiber ratio in soleus
      muscles, which were all ameliorated by MSC transplantation. Sural nerve
      morphometry showed decreased axonal circularity in STZ-induced diabetic rats,
      which was normalized by MSC transplantation. CONCLUSIONS: These results suggest
      that MSC transplantation could have therapeutic effects on DPN through paracrine
      actions of growth factors secreted by MSCs.

PMID- 18728234
TI  - Ablation of AMP-activated protein kinase alpha2 activity exacerbates insulin
      resistance induced by high-fat feeding of mice.
AB  - OBJECTIVE: We determined whether muscle AMP-activated protein kinase (AMPK) has a
      role in the development of insulin resistance. RESEARCH DESIGN AND METHODS:
      Muscle-specific transgenic mice expressing an inactive form of the AMPK alpha2
      catalytic subunit (alpha2i TG) and their wild-type littermates were fed either a
      high-fat (60% kcal fat) or a control (10% kcal fat) diet for 30 weeks. RESULTS:
      Compared with wild-type mice, glucose tolerance in alpha2i TG mice was slightly
      impaired on the control diet and significantly impaired on the high-fat diet. To
      determine whether the whole-body glucose intolerance was associated with impaired
      insulin sensitivity in skeletal muscle, glucose transport in response to
      submaximal insulin (450 microU/ml) was measured in isolated soleus muscles. On
      the control diet, insulin-stimulated glucose transport was reduced by
      approximately 50% in alpha2i TG mice compared with wild-type mice. High-fat
      feeding partially decreased insulin-stimulated glucose transport in wild-type
      mice, while high-fat feeding resulted in a full blunting of insulin-stimulated
      glucose transport in the alpha2i TG mice. High-fat feeding in alpha2i TG mice was
      accompanied by decreased expression of insulin signaling proteins in
      gastrocnemius muscle. CONCLUSIONS: The lack of skeletal muscle AMPK alpha2
      activity exacerbates the development of glucose intolerance and insulin
      resistance caused by high-fat feeding and supports the thesis that AMPK alpha2 is
      an important target for the prevention/amelioration of skeletal muscle insulin
      resistance through lifestyle (exercise) and pharmacologic (e.g., metformin)
      treatments.

PMID- 18728235
TI  - Screening uptake in a well-established diabetic retinopathy screening program:
      the role of geographical access and deprivation.
AB  - OBJECTIVE: To identify criteria that affect uptake of diabetes retinal screening
      in a community screening program using mobile retinal digital photography units.
      RESEARCH DESIGN AND METHODS: Data from the regional diabetes population-based
      retinal screening program and regional ophthalmology laser database were linked
      to patient postal code (zip code) data. We used distance from retinal screening
      event, social deprivation scores, and demographic information to identify risk
      factors for nonattendance at a diabetes retinal screening event. Patients were
      subdivided into urban (>125,000 population), other urban (3,000-125,000
      population), or rural (<3,000 population) depending on where they lived. Data
      were collected from 2004 to 2006 inclusive and included 15,150 patients and
      32,621 eye screening records. RESULTS: The mean +/- SD age of patients was 63 +/-
      15 years, and 54% were male. Mean travel time to retinal screening event varied
      from 7.1 to 17.0 min. For 12% of missed appointments, patients were more likely
      to be younger, to have longer diabetes duration, to have poor A1C and blood
      pressure control, to be smokers, and to live in deprived areas. Poor attendance
      was not associated with sex or distance to retinal screening event. CONCLUSIONS:
      Social deprivation is strongly associated with poor attendance at retinal
      screening events. Time traveled to screening event was not associated with
      attendance in this study of a mobile retinal screening service, which visited
      general practitioner surgeries. This data can help inform population-based
      diabetes retinal screening programs about improving patient uptake.

PMID- 18728236
TI  - Diabetes-related symptom distress in association with glucose metabolism and
      comorbidity: the Hoorn Study.
AB  - OBJECTIVE: The purpose of this study was to determine the associations between
      diabetes-related symptom distress, glucose metabolism status, and comorbidities
      of type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a cross-sectional
      sample of 281 individuals with normal glucose metabolism (NGM), 181 individuals
      with impaired glucose metabolism (IGM), and 107 subjects with type 2 diabetes. We
      used the revised type 2 Diabetes Symptom Checklist (DSC-R) to assess diabetes
      related symptom distress. RESULTS: The total symptom distress score (range 0-100)
      was relatively low for diabetic subjects (mean +/- SD 8.4 +/- 9.4), although it
      was significantly different from that for subjects with IGM (6.5 +/- 7.1) and NGM
      (6.1 +/- 7.9) (F = 3.1, 2 d.f., P = 0.046). Ischemic heart disease was associated
      with elevated DSC-R scores on three subscales, whereas depression showed higher
      symptom distress levels across all DSC-R domains. CONCLUSIONS: Worsening glucose
      metabolism is associated with increasing diabetes-related symptom distress. This
      relationship is attenuated by ischemic heart disease and particularly by
      depression.

PMID- 18728238
TI  - Measuring several aspects of attention in one test: the factor structure of
      conners's continuous performance test.
AB  - OBJECTIVE: Continuous performance tests are known to typically measure sustained
      attention but usually also yield parameters that potentially measure other
      subprocesses of attention. The aim of the present study was to test the factor
      structure of the Conners's Continuous Performance Test (CCPT) in a heterogeneous
      clinical sample consisting of subjects considered to fail in different
      subfunctions of attention. METHOD AND RESULTS: CCPT records from 376 patients
      were factor analyzed, yielding five factors indicating a differentiation between
      focused attention, hyperactivity-impulsivity, sustained attention, vigilance, and
      change in control. CONCLUSION: The study warns against reducing CCPT performance
      to one overall score of attention. The study further emphasizes the need to
      reserve the concept of sustained attention for measures of change as a function
      of time on task. The differentiation between sustained attention and vigilance
      and the concept of change in mental control during the test are possible
      methodological contributions of the study.

PMID- 18728239
TI  - Evidence for an asialoglycoprotein receptor on nonparenchymal cells for O-linked
      glycoproteins.
AB  - B cell-activating factor receptor 3 (BR3)-Fc is an IgG1-receptor dimeric fusion
      protein that has multiple O-linked glycosylation sites and sialylation levels
      that can vary in the manufacturing process. Increased sialic acid levels resulted
      from increased site occupancy with the O-linked N-acetylgalactosamine (GalNAc
      Gal), but because the ratio of sialic acid per mole of oligosaccharide remained
      approximately 1, this led to increased asialo terminal GalNAc. Previous studies
      have demonstrated an effect of terminal asialo Gal or GalNAc on the clearance of
      glycoproteins due to uptake and degradation by lectin receptors in the liver.
      However, the previous studies examined N-linked oligosaccharides, and there are
      less data regarding O-linked oligosaccharides. The objective of these studies was
      to determine the effects on the pharmacokinetics and distribution of the asialo
      terminal GalNAc and varying amounts of sialic acid residues on BR3-Fc. The
      results of the data presented here suggest that exposed Gal on the desialylated
      BR3-Fc led to rapid clearance due to uptake and degradation in the liver that was
      associated with nonparenchymal cells. It is interesting to note that the data
      indicated a decreased clearance and increased exposure of BR3-Fc as the sialic
      acid levels increased, even though increased sialic acid was associated with
      increased asialo GalNAc. Therefore, the exposed GalNAc did not seem to play a
      role in the clearance of BR3-Fc; although the Gal linked to the hydroxyl group at
      position 3 may have prevented an interaction. Because we did not see uptake of
      desialylated BR3-Fc in hepatocytes where the asialoglycoprotein receptor is
      localized, this nonparenchymal cell lectin may have preference for O-linked
      glycoproteins.

PMID- 18728240
TI  - Clotrimazole ameliorates intestinal inflammation and abnormal angiogenesis by
      inhibiting interleukin-8 expression through a nuclear factor-kappaB-dependent
      manner.
AB  - Increased interleukin (IL)-8 plays an important role not only in activation and
      recruitment of neutrophils but also in inducing exaggerated angiogenesis at the
      inflamed site. In the present study, we investigated the fact that clotrimazole
      (CLT) inhibits intestinal inflammation, and the inhibitory action is mediated
      through suppression of IL-8 expression. In the trinitrobenzene sulfonic acid
      (TNBS)-induced rat colitis model, CLT dose-dependently protected from the TNBS
      induced weight loss, colon ulceration, and myeloperoxidase activity increase. In
      the lesion site, CLT also suppressed the TNBS-induced angiogenesis, IL-8
      expression, and nuclear factor (NF)-kappaB activation. In a cellular model of
      colitis using tumor necrosis factor (TNF)-alpha-stimulated HT29 colon epithelial
      cells, treatment with CLT significantly suppressed TNF-alpha-mediated IL-8
      induction and NF-kappaB transcriptional activity revealed by a luciferase
      reporter gene assay. Furthermore, cotreatment with CLT and pyrrolidine
      dithiocarbamate, a NF-kappaB inhibitor, synergistically reduced the NF-kappaB
      transcriptional activity as well as IL-8 expression. In an in vitro angiogenesis
      assay, CLT suppressed IL-8-induced proliferation, tube formation, and invasion of
      human umbilical vein endothelial cells. The in vivo angiogenesis assay using
      chick chorioallantoic membrane also showed that CLT significantly inhibited the
      IL-8-induced formation of new blood vessels. Taken together, these results
      suggest that CLT may prevent the progression of intestinal inflammation by not
      only down-regulating IL-8 expression but also inhibiting the action of IL-8 in
      both colon epithelial and vascular endothelial cells during pathogenesis of
      intestinal inflammation.

PMID- 18728243
TI  - Evaluation of the administration time effect on the cumulative cortisol
      suppression and cumulative lymphocytes suppression for once-daily inhaled
      corticosteroids: a population modeling/simulation approach.
AB  - Inhaled glucocorticoids continue to be first-line therapy in asthma. To improve
      improving patient compliance, newer inhaled glucocorticoids have been developed
      for once-a-day treatment. This study was interested in identifying the optimal
      time of dosing using 2 surrogate markers of glucocorticoid action. A previously
      published study on the pharmacokinetics and pharmacodynamics (cortisol and blood
      lymphocyte suppression) of the inhaled glucocorticoids budesonide and fluticasone
      propionate was reanalyzed using a population pharmacokinetic approach. A
      stochastic numerical simulation using NONMEM assessed the effects of time of
      dosing on cortisol (side effect parameter) and blood lymphocytes (side effect and
      effect parameter). The effects on cortisol were more pronounced when the
      glucocorticoids were given in the morning, whereas the effects on lymphocytes (an
      effect controlled by endogenous and exogenous glucocorticoids) were maximized
      when dosing occurred in the late afternoon or evening. Twice-daily dosing of the
      same dose resulted in smaller differences between maximum and minimal effects.
      These were of no clinical relevance. Simulations for once-daily dosing support
      clinical studies that reported a higher antiasthmatic effect and lower cortisol
      suppression when once-daily dosing occurs in the evening.

PMID- 18728242
TI  - Evaluation of a [13C]-dextromethorphan breath test to assess CYP2D6 phenotype.
AB  - A [(13)C]-dextromethorphan ([(13)C]-DM) breath test was evaluated to assess its
      feasibility as a rapid, phenotyping assay for CYP2D6 activity. [(13)C]-DM (0.5
      mg/kg) was administered orally with water or potassium bicarbonate-sodium
      bicarbonate to 30 adult Caucasian volunteers (n=1 each): CYP2D6 poor metabolizers
      (2 null alleles; PM-0) and extensive metabolizers with 1 (EM-1) or 2 functional
      alleles (EM-2). CYP2D6 phenotype was determined by (13)CO(2) enrichment measured
      by infrared spectrometry (delta-over-baseline [DOB] value) in expired breath
      samples collected before and up to 240 minutes after [(13)C]-DM ingestion and by
      4-hour urinary metabolite ratio. The PM-0 group was readily distinguishable from
      either EM group by both the breath test and urinary metabolite ratio. Using a
      single point determination of phenotype at 40 minutes and defining PMs as
      subjects with a DOB <or=0.5, the sensitivity of the method was 100%; specificity
      was 95% with 95% accuracy and resulted in the misclassification of 1 EM-1
      individual as a PM. Modification of the initial protocol (timing of potassium
      bicarbonate-sodium bicarbonate administration relative to dose) yielded
      comparable results, but there was a tendency toward increased DOB values.
      Although further development is required, these studies suggest that the [(13)C]
      DM breath test offers promise as a rapid, minimally invasive phenotyping assay
      for CYP2D6 activity.

PMID- 18728244
TI  - ABC-transporters expressed on endothelial cell membranes efflux anti-HIV drugs.

PMID- 18728241
TI  - Pharmacokinetics of efavirenz when co-administered with rifampin in TB/HIV co
      infected patients: pharmacogenetic effect of CYP2B6 variation.
AB  - The goal of this study was to determine the effect of CYP2B6 genetic variation on
      the steady-state pharmacokinetics of efavirenz (600 mg/d) in TB/HIV co-infected
      patients receiving concomitant rifampin, a potent CYP inducer. In the 26 patients
      studied, CYP2B6 c.516GG, GT, and TT genotype frequencies were 0.27, 0.50, and
      0.23, respectively. Mean plasma efavirenz area under the curve was significantly
      higher in patients with CYP2B6 c.516TT than in those with GT (107 vs 27.6 microg
      x h/mL, P< .0001) or GG genotype (107 vs 23.0 microg x h/mL, P< .0001). Apparent
      oral clearance (CL/F) was significantly lower in patients with CYP2B6 c.516TT
      than in those with GT genotype (2.1 vs 8.4 mL/min/kg, P<0.0001) and GG genotype
      (2.1 vs 9.9 mL/min/kg, P< .0001). No differences in efavirenz exposure or CL/F
      existed between patients with CYP2B6 c.516GT and GG genotypes. Our results
      indicate that CYP2B6 c.516TT genotype can be used to identify efavirenz poor
      metabolizers in patients co-treated with rifampin.

PMID- 18728245
TI  - Retraction. Blood concentrations of Th2-type immunoglobulins are selectively
      increased in weanling mice subjected to acute malnutrition.

PMID- 18728247
TI  - Clinical and immunologic consequences of a somatic reversion in a patient with X
      linked severe combined immunodeficiency.
AB  - X-linked severe combined immunodeficiency is a life-threatening disorder caused
      by mutations in the gene encoding the interleukin-2 receptor gamma chain (IL2RG).
      Hypomorphic mutations and reversion of mutations in subpopulations of cells can
      result in variant clinical phenotypes, making diagnosis and treatment difficult.
      We describe a 5-year-old boy with mild susceptibility to infection who was
      investigated for a mutation in IL2RG due to persistent natural killer (NK)- and T
      cell lymphopenia. A functionally relevant novel T466C point mutation was found in
      B, NK, and epithelial cells, whereas alpha/beta and gamma/delta T cells showed
      the normal gene sequence, suggesting reversion of the mutation in a common T-cell
      precursor. This genetic correction in T cells resulted in a diverse T-cell
      repertoire and significant immunity despite failure to produce specific
      antibodies linked to an intrinsic defect of mutant B cells. These observations
      confirm the potential of revertant T-cell precursors to reconstitute immune
      function, but questions remain on the longevity of revertant cells implicating
      the need for careful follow up and early consideration of hematopoietic stem cell
      transplantation (HSCT).

PMID- 18728246
TI  - Expression of angiotensin-converting enzyme (CD143) identifies and regulates
      primitive hemangioblasts derived from human pluripotent stem cells.
AB  - We report that angiotensin-converting enzyme (ACE), a critical physiologic
      regulator of blood pressure, angiogenesis, and inflammation, is a novel marker
      for identifying hemangioblasts differentiating from human embryonic stem cells
      (hESC). We demonstrate that ACE+CD45-CD34+/- hemangioblasts are common yolk sac
      (YS)-like progenitors for not only endothelium but also both primitive and
      definitive human lymphohematopoietic cells. Thrombopoietin and basic fibroblast
      growth factor are identified as critical factors for the proliferation of human
      hemangioblasts. The developmental sequence of human embryoid body hematopoiesis
      is remarkably congruent to the timeline of normal human YS development, which
      occurs during weeks 2 to 6 of human gestation. Furthermore, ACE and the renin
      angiotensin system (RAS) directly regulate hemangioblast expansion and
      differentiation via signaling through the angiotensin II receptors AGTR1 and
      AGTR2. ACE enzymatic activity is required for hemangioblast expansion, and
      differentiation toward either endothelium or multipotent hematopoietic
      progenitors is dramatically augmented after manipulation of angiotensin II
      signaling with either AGTR1- or AGTR2-specific inhibitors. The RAS can therefore
      be exploited to direct the hematopoietic or endothelial fate of hESC-derived
      hemangioblasts, thus providing novel opportunities for human tissue engineering.
      Moreover, the initial events of human hematoendotheliogenesis can be delineated
      in a manner previously impossible because of inaccessibility to early human
      embryonic tissues.

PMID- 18728249
TI  - The cover. Telephone.

PMID- 18728250
TI  - Piece of my mind. Seventy-two hours.

PMID- 18728248
TI  - Telomerase activity of HIV-1-specific CD8+ T cells: constitutive up-regulation in
      controllers and selective increase by blockade of PD ligand 1 in progressors.
AB  - Exhaustion of virus-specific T cells may play an important role in the
      pathophysiology of chronic viral infections. Here, we analyzed telomere length
      and telomerase activity in HIV-1-specific CD8+ T cells from progressors or
      controllers to determine underlying molecular pathways of T-cell exhaustion and
      senescence. Telomere lengths of HIV-1-specific CD8+ T cells from progressors were
      significantly shorter compared with autologous cytomegalovirus (CMV)/Epstein-Barr
      virus (EBV)-specific CD8+ T cells or bulk CD8+ T cells, while telomere lengths
      from controllers significantly exceeded those of autologous bulk CD8+ T cells and
      reached a similar level as HIV-1-specific CD8+ T cells collected during primary
      HIV-1 infection. Telomere length stabilization in controllers corresponded to
      high levels of constitutive telomerase activity, which was associated with
      preservation of cytotoxic and proliferative properties. Conversely, limited
      constitutive telomerase activity was observed in HIV-1-specific CD8+ T cells from
      progressors, although an increase in both telomere length and telomerase activity
      was achieved in antigenic-peptide-stimulated cells from progressors after
      blocking the PD-1/PD ligand 1 (PD-L1) pathway. Collectively, these data suggest a
      causal role of telomere shortening for the functional deficiencies of HIV-1
      specific CD8+ T cells in chronic progressive infection, while high constitutive
      telomerase activities appears to contribute to maintenance of polyfunctional HIV
      1-specific CD8+ T cells from HIV-1 controllers.

PMID- 18728251
TI  - Groups target nursing school bottleneck to address medical workforce deficit.

PMID- 18728252
TI  - Federal government seeks to clarify the Americans with Disabilities Act.

PMID- 18728253
TI  - New guidelines issued for prevention and management of thrombosis.

PMID- 18728254
TI  - Guest authorship, mortality reporting, and integrity in rofecoxib studies.

PMID- 18728255
TI  - Guest authorship, mortality reporting, and integrity in rofecoxib studies.

PMID- 18728256
TI  - Guest authorship, mortality reporting, and integrity in rofecoxib studies.

PMID- 18728257
TI  - Guest authorship, mortality reporting, and integrity in rofecoxib studies.

PMID- 18728258
TI  - Guest authorship, mortality reporting, and integrity in rofecoxib studies.

PMID- 18728259
TI  - Guest authorship, mortality reporting, and integrity in rofecoxib studies.

PMID- 18728260
TI  - Guest authorship, mortality reporting, and integrity in rofecoxib studies.

PMID- 18728261
TI  - Guest authorship, mortality reporting, and integrity in rofecoxib studies.

PMID- 18728262
TI  - Guest authorship, mortality reporting, and integrity in rofecoxib studies.

PMID- 18728263
TI  - Guest authorship, mortality reporting, and integrity in rofecoxib studies.

PMID- 18728264
TI  - Nut, corn, and popcorn consumption and the incidence of diverticular disease.
AB  - CONTEXT: Patients with diverticular disease are frequently advised to avoid
      eating nuts, corn, popcorn, and seeds to reduce the risk of complications.
      However, there is little evidence to support this recommendation. OBJECTIVE: To
      determine whether nut, corn, or popcorn consumption is associated with
      diverticulitis and diverticular bleeding. DESIGN AND SETTING: The Health
      Professionals Follow-up Study is a cohort of US men followed up prospectively
      from 1986 to 2004 via self-administered questionnaires about medical (biennial)
      and dietary (every 4 years) information. Men reporting newly diagnosed
      diverticulosis or diverticulitis were mailed supplemental questionnaires.
      PARTICIPANTS: The study included 47,228 men aged 40 to 75 years who at baseline
      were free of diverticulosis or its complications, cancer, and inflammatory bowel
      disease and returned a food-frequency questionnaire. MAIN OUTCOME MEASURES:
      Incident diverticulitis and diverticular bleeding. RESULTS: During 18 years of
      follow-up, there were 801 incident cases of diverticulitis and 383 incident cases
      of diverticular bleeding. We found inverse associations between nut and popcorn
      consumption and the risk of diverticulitis. The multivariate hazard ratios for
      men with the highest intake of each food (at least twice per week) compared with
      men with the lowest intake (less than once per month) were 0.80 (95% confidence
      interval, 0.63-1.01; P for trend = .04) for nuts and 0.72 (95% confidence
      interval, 0.56-0.92; P for trend = .007) for popcorn. No associations were seen
      between corn consumption and diverticulitis or between nut, corn, or popcorn
      consumption and diverticular bleeding or uncomplicated diverticulosis.
      CONCLUSIONS: In this large, prospective study of men without known diverticular
      disease, nut, corn, and popcorn consumption did not increase the risk of
      diverticulosis or diverticular complications. The recommendation to avoid these
      foods to prevent diverticular complications should be reconsidered.

PMID- 18728265
TI  - Lead, mercury, and arsenic in US- and Indian-manufactured Ayurvedic medicines
      sold via the Internet.
AB  - CONTEXT: Lead, mercury, and arsenic have been detected in a substantial
      proportion of Indian-manufactured traditional Ayurvedic medicines. Metals may be
      present due to the practice of rasa shastra (combining herbs with metals,
      minerals, and gems). Whether toxic metals are present in both US- and Indian
      manufactured Ayurvedic medicines is unknown. OBJECTIVES: To determine the
      prevalence of Ayurvedic medicines available via the Internet containing
      detectable lead, mercury, or arsenic and to compare the prevalence of toxic
      metals in US- vs Indian-manufactured medicines and between rasa shastra and non
      rasa shastra medicines. DESIGN: A search using 5 Internet search engines and the
      search terms Ayurveda and Ayurvedic medicine identified 25 Web sites offering
      traditional Ayurvedic herbs, formulas, or ingredients commonly used in Ayurveda,
      indicated for oral use, and available for sale. From 673 identified products, 230
      Ayurvedic medicines were randomly selected for purchase in August-October 2005.
      Country of manufacturer/Web site supplier, rasa shastra status, and claims of
      Good Manufacturing Practices were recorded. Metal concentrations were measured
      using x-ray fluorescence spectroscopy. MAIN OUTCOME MEASURES: Prevalence of
      medicines with detectable toxic metals in the entire sample and stratified by
      country of manufacture and rasa shastra status. RESULTS: One hundred ninety-three
      of the 230 requested medicines were received and analyzed. The prevalence of
      metal-containing products was 20.7% (95% confidence interval [CI], 15.2%-27.1%).
      The prevalence of metals in US-manufactured products was 21.7% (95% CI, 14.6%
      30.4%) compared with 19.5% (95% CI, 11.3%-30.1%) in Indian products (P = .86).
      Rasa shastra compared with non-rasa shastra medicines had a greater prevalence of
      metals (40.6% vs 17.1%; P = .007) and higher median concentrations of lead (11.5
      microg/g vs 7.0 microg/g; P = .03) and mercury (20,800 microg/g vs 34.5 microg/g;
      P = .04). Among the metal-containing products, 95% were sold by US Web sites and
      75% claimed Good Manufacturing Practices. All metal-containing products exceeded
      1 or more standards for acceptable daily intake of toxic metals. CONCLUSION: One
      fifth of both US-manufactured and Indian-manufactured Ayurvedic medicines
      purchased via the Internet contain detectable lead, mercury, or arsenic.

PMID- 18728266
TI  - Effect of allopurinol on blood pressure of adolescents with newly diagnosed
      essential hypertension: a randomized trial.
AB  - CONTEXT: Hyperuricemia is a predictor for the development of hypertension and is
      commonly present in new-onset essential hypertension. Experimentally increasing
      uric acid levels using a uricase inhibitor causes systemic hypertension in animal
      models. OBJECTIVE: To determine whether lowering uric acid lowers blood pressure
      (BP) in hyperuricemic adolescents with newly diagnosed hypertension. DESIGN,
      SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled, crossover
      trial (September 2004-March 2007) involving 30 adolescents (aged 11-17 years) who
      had newly diagnosed, never-treated stage 1 essential hypertension and serum uric
      acid levels > or = 6 mg/dL. Participants were treated at the Pediatric
      Hypertension Clinic at Texas Children's Hospital in Houston. Patients were
      excluded if they had stage 2 hypertension or known renal, cardiovascular,
      gastrointestinal tract, hepatic, or endocrine disease. INTERVENTION: Allopurinol,
      200 mg twice daily for 4 weeks, and placebo, twice daily for 4 weeks, with a 2
      week washout period between treatments. The order of the treatments was
      randomized. MAIN OUTCOME MEASURES: Change in casual and ambulatory blood
      pressure. RESULTS: For casual BP, the mean change in systolic BP for allopurinol
      was -6.9 mm Hg (95% confidence interval [CI], -4.5 to -9.3 mm Hg) vs -2.0 mm Hg
      (95% CI, 0.3 to -4.3 mm Hg; P = .009) for placebo, and the mean change in
      diastolic BP for allopurinol was -5.1 mm Hg (95% CI, -2.5 to -7.8 mm Hg) vs -2.4
      (95% CI, 0.2 to -4.1; P = .05) for placebo. Mean change in mean 24-hour
      ambulatory systolic BP for allopurinol was -6.3 mm Hg (95% CI, -3.8 to -8.9 mm
      Hg) vs 0.8 mm Hg (95% CI, 3.4 to -2.9 mm Hg; P = .001) for placebo and mean 24
      hour ambulatory diastolic BP for allopurinol was -4.6 mm Hg (-2.4 to -6.8 mm Hg)
      vs -0.3 mm Hg (95% CI, 2.3 to -2.1 mm Hg; P = .004) for placebo. Twenty of the 30
      participants achieved normal BP by casual and ambulatory criteria while taking
      allopurinol vs 1 participant while taking placebo (P < .001). CONCLUSIONS: In
      this short-term, crossover study of adolescents with newly diagnosed
      hypertension, treatment with allopurinol resulted in reduction of BP. The results
      represent a new potential therapeutic approach, although not a fully developed
      therapeutic strategy due to potential adverse effects. These preliminary findings
      require confirmation in larger clinical trials. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00288184.

PMID- 18728267
TI  - Benefits and risks of tight glucose control in critically ill adults: a meta
      analysis.
AB  - CONTEXT: The American Diabetes Association and Surviving Sepsis Campaign
      recommend tight glucose control in critically ill patients based largely on 1
      trial that shows decreased mortality in a surgical intensive care unit. Because
      similar studies report conflicting results and tight glucose control can cause
      dangerous hypoglycemia, the data underlying this recommendation should be
      critically evaluated. OBJECTIVE: To evaluate benefits and risks of tight glucose
      control vs usual care in critically ill adult patients. DATA SOURCES: MEDLINE
      (1950-2008), the Cochrane Library, clinical trial registries, reference lists,
      and abstracts from conferences from both the American Thoracic Society (2001
      2008) and the Society of Critical Care Medicine (2004-2008). STUDY SELECTION: We
      searched for studies in any language in which adult intensive care patients were
      randomly assigned to tight vs usual glucose control. Of 1358 identified studies,
      34 randomized trials (23 full publications, 9 abstracts, 2 unpublished studies)
      met inclusion criteria. DATA EXTRACTION AND ANALYSIS: Two reviewers independently
      extracted information using a prespecified protocol and evaluated methodological
      quality with a standardized scale. Study investigators were contacted for missing
      details. We used both random- and fixed-effects models to estimate relative risks
      (RRs). RESULTS: Twenty-nine randomized controlled trials totaling 8432 patients
      contributed data for this meta-analysis. Hospital mortality did not differ
      between tight glucose control and usual care overall (21.6% vs 23.3%; RR, 0.93;
      95% confidence interval [CI], 0.85-1.03). There was also no significant
      difference in mortality when stratified by glucose goal ([1] very tight: < or =
      110 mg/dL; 23% vs 25.2%; RR, 0.90; 95% CI, 0.77-1.04; or [2] moderately tight: <
      150 mg/dL; 17.3% vs 18.0%; RR, 0.99; 95% CI, 0.83-1.18) or intensive care unit
      setting ([1] surgical: 8.8% vs 10.8%; RR, 0.88; 95% CI, 0.63-1.22; [2] medical:
      26.9% vs 29.7%; RR, 0.92; 95% CI, 0.82-1.04; or [3] medical-surgical: 26.1% vs
      27.0%; RR, 0.95; 95% CI, 0.80-1.13). Tight glucose control was not associated
      with significantly decreased risk for new need for dialysis (11.2% vs 12.1%; RR,
      0.96; 95% CI, 0.76-1.20), but was associated with significantly decreased risk of
      septicemia (10.9% vs 13.4%; RR, 0.76; 95% CI, 0.59-0.97), and significantly
      increased risk of hypoglycemia (glucose < or= 40 mg/dL; 13.7% vs 2.5%; RR, 5.13;
      95% CI, 4.09-6.43). CONCLUSION: In critically ill adult patients, tight glucose
      control is not associated with significantly reduced hospital mortality but is
      associated with an increased risk of hypoglycemia.

PMID- 18728268
TI  - Opt-out testing for human immunodeficiency virus in the United States: progress
      and challenges.
AB  - The Centers for Disease Control and Prevention (CDC) has recommended human
      immunodeficiency virus (HIV) testing for all persons aged 13 to 64 years in all
      health care settings. Signed consent would not be required and counseling with
      referral would be managed as it is for other serious conditions. The goal of the
      recommendations is to promote earlier entry into care to reduce unnecessary
      mortality and facilitate prevention by behavioral changes that accompany
      knowledge of serostatus. Concerns about the change include laws in some states
      that mandate signed consent and counseling, a perception that counseling is an
      effective prevention strategy, variability in payment coverage for the test,
      concerns about the stigma and discrimination that may accompany the HIV
      diagnosis, and the possibility that other testing policies would be more
      effective. Eleven of 16 states have changed legislation to reduce barriers to
      testing, 35 of 74 national professional societies have endorsed the new
      recommendations, and multiple demonstration projects have shown feasibility.
      Metrics to evaluate the health outcomes of the CDC's recommendations for HIV
      testing have been defined, but the data necessary to determine the effects on
      early entry into care, the actual reduction in disease incidence, and the
      unanticipated consequences are not yet available.

PMID- 18728269
TI  - Opportunities for enhancing the FDA guidance on pharmacovigilance.

PMID- 18728270
TI  - Single-patient rooms for safe patient-centered hospitals.

PMID- 18728271
TI  - Food safety for the 21st century.

PMID- 18728272
TI  - Yellow fever: 100 years of discovery.

PMID- 18728274
TI  - JAMA patient page. Yellow fever.

PMID- 18728273
TI  - Tight glycemic control in critically ill adults.

PMID- 18728275
TI  - Leaders worry that U.S. is losing edge on cancer clinical trials.

PMID- 18728276
TI  - Crackdown on unproven cancer treatments focuses on internet marketers.

PMID- 18728278
TI  - StatBite: Cancer incidence among HIV-infected individuals in the U.S., 2000-2003.

PMID- 18728277
TI  - Major treatment improvements encourage kidney cancer researchers to seek further
      gains.

PMID- 18728279
TI  - Speeding up the evaluation of new agents in cancer.
AB  - Despite both the increase in basic biologic knowledge and the fact that many new
      agents have reached various stages of development during the last 10 years, the
      number of new treatments that have been approved for patients has not increased
      as expected. We propose the multi-arm, multi-stage trial design as a way to
      evaluate treatments faster and more efficiently than current standard trial
      designs. By using intermediate outcomes and testing a number of new agents (and
      combinations) simultaneously, the new design requires fewer patients. Three
      trials using this methodology are presented.

PMID- 18728280
TI  - SDHB--a gene for all tumors?

PMID- 18728281
TI  - Association of ACE inhibitors and angiotensin receptor blockers with keratinocyte
      cancer prevention in the randomized VATTC trial.
AB  - BACKGROUND: The observation that angiotensin II is a potent angiogenic and growth
      factor raises the possibility that blocking its effects could reduce the
      incidence of cancer. We evaluated associations between use of angiotensin
      converting enzyme (ACE) inhibitors and of angiotensin receptor blockers (ARBs)
      and keratinocyte cancer incidence in a population at high risk of the disease.
      METHODS: A cohort study design was conducted using data on 1051 participants in
      the randomized Department of Veterans Affairs Topical Tretinoin Chemoprevention
      (VATTC) Trial, all of whom were at increased risk of basal cell carcinoma (BCC)
      or squamous cell carcinoma (SCC). We followed participants from enrollment
      (November 1998 through January 2003) until first BCC or SCC. Study participants
      were examined every 6 months by a study dermatologist; biopsies were taken on all
      suspicious lesions and centrally reviewed. Use of ACE inhibitors and ARBs was
      ascertained from VA pharmacy records. Cox proportional hazards models were used
      to estimate adjusted incidence rate ratios (IRRs) and 95% confidence intervals
      (CIs) of BCC and SCC with use of ACE inhibitors or ARBs. RESULTS: During a median
      follow-up of 3.4 years, 472 incident BCCs, 309 SCCs, and 200 deaths from any
      cause were observed. Compared with nonusers, users of ACE inhibitors or ARBs had
      statistically significantly reduced risks of BCC (IRR(BCC) = 0.61, 95% CI = 0.50
      to 0.76) and SCC (IRR(SCC) = 0.67, 95% CI = 0.52 to 0.87). The combined absolute
      incidence rates of BCC and SCC were 237 per 1000 person-years among users of ACE
      inhibitors or ARBs and 374 per 1000 person-years among nonusers. The greatest
      reduction in keratinocyte cancer was seen among people who initiated use of ACE
      inhibitors or ARBs during the study period (IRR(BCC) = 0.45 [95% CI = 0.34 to
      0.59]; IRR(SCC) = 0.48 [95% CI = 0.35 to 0.67]). CONCLUSION: Among a high-risk
      group of veterans, users of ACE inhibitors or ARBs had a lower incidence of
      keratinocyte cancers than nonusers. The more pronounced reduction among those who
      initiated use during the study may indicate an immediate effect.

PMID- 18728282
TI  - Nonmelanoma skin cancer and risk for subsequent malignancy.
AB  - BACKGROUND: Individuals with a personal history of nonmelanoma skin cancer (NMSC)
      may have an increased risk of subsequent noncutaneous malignancies. To test this
      hypothesis, we carried out a community-based, prospective cohort study. METHODS:
      In the CLUE (Give Us a Clue to Cancer and Heart Disease) II cohort, which was
      established in Washington County, MD, in 1989, the risk of new malignancies was
      compared among individuals with (n = 769) and without (n = 18,405) a personal
      history of NMSC (total n = 19,174) during a 16-year follow-up period.
      Pathologically confirmed NMSC (and other malignancies) were ascertained from the
      Washington County Cancer Registry. Cox regression analysis with time-dependent
      covariates was used to determine the hazard ratios (presented as multivariable
      adjusted relative risks [RRs]) and 95% confidence intervals (CIs) of second
      primary malignancies associated with a previously confirmed NMSC diagnosis. All
      statistical tests were two-sided. RESULTS: The crude incidence rate (per 10,000
      person-years) of subsequent cancers other than NMSC among participants with a
      positive personal history of NMSC was 293.5 and with a negative history was 77.8.
      Compared with persons with no personal history of NMSC, those with such a history
      had a statistically significantly increased risk of being diagnosed with a
      subsequent cancer other than NMSC (RR = 1.99, 95% CI = 1.70 to 2.33) after
      adjusting for age, sex, body mass index, smoking status, and educational level.
      The association was observed for both basal cell carcinoma (multivariable
      adjusted RR = 2.03, 95% CI = 1.70 to 2.42) and squamous cell carcinoma
      (multivariable-adjusted RR = 1.97, 95% CI = 1.50 to 2.59) of the skin. NMSC was a
      statistically significantly stronger cancer risk factor in younger age groups
      than in older age groups (P for interaction = .022). CONCLUSIONS: This community
      based, prospective cohort study provides evidence for an association between an
      NMSC diagnosis and an increased risk of subsequent cancer, even after adjusting
      for individual-level risk factors.

PMID- 18728283
TI  - Germline SDHB mutations and familial renal cell carcinoma.
AB  - Familial renal cell carcinoma (RCC) is a heterogeneous disorder that is most
      commonly caused by germline mutations in the VHL, MET, and FLCN genes or by
      constitutional chromosome 3 translocations. However, for many patients with
      familial RCC, the genetic basis of the disease is undefined. We investigated
      whether germline mutations in fumarate hydratase (FH) or succinate dehydrogenase
      subunit genes (SDHB, SDHC, SDHD) were associated with RCC susceptibility in 68
      patients with no clinical evidence of an RCC susceptibility syndrome. No
      mutations in FH, SDHC, or SDHD were identified in probands, but 3 of the 68
      (4.4%) probands had a germline SDHB mutation. Patients with a germline SDHB
      mutation presented with familial RCC (n = 1) or bilateral RCC (n = 2) and no
      personal or family history of pheochromocytoma or head and neck paraganglioma.
      Age at diagnosis of RCC in SDHB mutation carriers ranged from 24 to 73 years.
      These findings 1) demonstrate that patients with suspected inherited RCC should
      be examined for germline SDHB mutations, 2) suggest that all identified SDHB
      mutation carriers should be offered surveillance for RCC, and 3) provide a
      further link between familial RCC and activation of hypoxic-gene response
      pathways.

PMID- 18728284
TI  - Identification of chromatin remodeling genes Arid4a and Arid4b as leukemia
      suppressor genes.
AB  - BACKGROUND: Leukemia evolves through a multistep process from premalignancy to
      malignancy. Epigenetic alterations, including histone modifications, have been
      proposed to play an important role in tumorigenesis. The involvement of two
      chromatin remodeling genes, retinoblastoma-binding protein 1 (Rbbp1/Arid4a) and
      Rbbp1-like 1 (Rbbp1l1/Arid4b), in leukemogenesis was not characterized. METHODS:
      The leukemic phenotype of mice deficient for Arid4a with or without
      haploinsufficiency for Arid4b was investigated by serially monitoring complete
      blood counts together with microscopic histologic analysis and flow cytometric
      analysis of bone marrow and spleen from the Arid4a(-/-) mice or Arid4a(-/
      )Arid4b(+/-) mice. Regulation in bone marrow cells of downstream genes important
      for normal hematopoiesis was analyzed by reverse transcription-polymerase chain
      reaction. Genotypic effects on histone modifications were examined by western
      blotting and immunofluorescence analysis. All statistical tests were two-sided.
      RESULTS: Young (2-5 months old) Arid4a-deficient mice had ineffective blood cell
      production in all hematopoietic lineages. Beyond 5 months of age, the Arid4a(-/-)
      mice manifested monocytosis, accompanied by severe anemia and thrombocytopenia.
      These sick Arid4a(-/-) mice showed bone marrow failure with myelofibrosis
      associated with splenomegaly and hepatomegaly. Five of 42 Arid4a(-/-) mice and 10
      of 12 Arid4a(-/-)Arid4b(+/-) mice progressed to acute myeloid leukemia (AML) and
      had rapid further increases of leukocyte counts. Expression of Hox genes (Hoxb3,
      Hoxb5, Hoxb6, and Hoxb8) was decreased in Arid4a-deficient bone marrow cells with
      or without Arid4b haploinsufficiency, and FoxP3 expression was reduced in Arid4a(
      /-)Arid4b(+/-) bone marrow. Increases of histone trimethylation of H3K4, H3K9,
      and H4K20 (fold increases in trimethylation = 32, 95% confidence interval [CI] =
      27 to 32; 45, 95% CI = 41 to 49; and 2.2, 95% CI = 1.7 to 2.7, respectively) were
      observed in the bone marrow of Arid4a-deficient mice. CONCLUSIONS: Arid4a
      deficient mice initially display ineffective hematopoiesis, followed by
      transition to chronic myelomonocytic leukemia (CMML)-like
      myelodysplastic/myeloproliferative disorder, and then transformation to AML. The
      disease processes in the Arid4a-deficient mice are very similar to the course of
      events in humans with CMML and AML. This mouse model has the potential to furnish
      additional insights into the role of epigenetic alterations in leukemogenesis,
      and it may be useful in developing novel pharmacological approaches to treatment
      of preleukemic and leukemic states.

PMID- 18728286
TI  - Re: Intensity-modulated radiation therapy dose prescription, recording, and
      delivery: patterns of variability among institutions and treatment planning
      systems.

PMID- 18728285
TI  - Induction of apoptosis in human cancer cells by candidaspongiolide, a novel
      sponge polyketide.
AB  - BACKGROUND: Candidaspongiolide (CAN), a novel polyketide from a marine sponge, is
      the active component of a mixture that was found to be potently cytotoxic in the
      National Cancer Institute's 60-cell-line screen. METHODS: Effects of CAN on U251
      glioma and HCT116 colorectal cancer cells and on normal fibroblasts were assessed
      using radiolabeling studies to measure protein synthesis, clonogenic assays to
      measure cell survival, flow cytometry of annexin V- and propidium iodide-stained
      cells to measure apoptosis, and western blots in the presence or absence of
      specific inhibitors to assess accumulation and phosphorylation of potential
      downstream target proteins. RESULTS: CAN inhibited protein synthesis and potently
      induced apoptosis in both U251 and HCT116 cells, the latter in part by a caspase
      12-dependent pathway. For example, 25%-30% of U251 or HCT116 cells became
      apoptotic after 24 hours of treatment with 100 nM CAN. CAN also rapidly induced
      sustained phosphorylation of eukaryotic translation initiation factor-2 (eIF2)
      alpha at Ser51 and of the translation elongation factor eEF2 at Thr56, which
      could contribute to its dose-dependent inhibition of protein synthesis. Stable
      expression of dominant-negative eIF2alpha was sufficient to prevent CAN-induced
      eIF2alpha phosphorylation and induction of apoptosis but insufficient to prevent
      inhibition of protein synthesis. CAN induction of eIF2alpha phosphorylation did
      not occur by a classic endoplasmic reticulum stress pathway. However, an
      inhibitor of and small-interfering RNAs to the double-stranded RNA-dependent
      protein kinase PKR prevented CAN-mediated eIF2alpha phosphorylation and
      apoptosis, respectively. Although CAN inhibited protein synthesis in both cancer
      cells and normal human fibroblasts, it induced eIF2alpha phosphorylation and
      apoptosis only in cancer cells. CONCLUSIONS: CAN triggers PKR/eIF2alpha/caspase
      12-dependent apoptosis and inhibits protein synthesis in cancer cells but only
      inhibits protein synthesis in normal cells.

PMID- 18728287
TI  - Re: Intensity-modulated radiation therapy dose prescription, recording, and
      delivery: patterns of variability among institutions and treatment planning
      systems.

PMID- 18728289
TI  - Re: Intensity-modulated radiation therapy dose prescription, recording, and
      delivery: patterns of variability among institutions and treatment planning
      systems.

PMID- 18728288
TI  - Re: Intensity-modulated radiation therapy dose prescription, recording, and
      delivery: patterns of variability among institutions and treatment planning
      systems.

PMID- 18728290
TI  - CYP7A1 promoter polymorphism -203A>C affects bile salt synthesis rate in patients
      after ileal resection.
AB  - Cholesterol 7alpha-hydroxylase (CYP7A1) plays a crucial role in cholesterol
      metabolism and has been implicated in genetic susceptibility to atherosclerosis.
      Thus, an understanding of its transcriptional regulation is of considerable
      importance. We evaluated the effect of a common -203A>C polymorphism in the
      CYP7A1 promoter region on the activity of CYP7A1, estimated as the ratios of
      serum 7alpha-hydroxycholest-4-en-3-one (C4) to either total or non-HDL
      cholesterol. The study was performed on patients after resection of the distal
      ileum, leading to upregulation of CYP7A1 activity (n = 65). Healthy volunteers
      served as the control group (n = 66). Whereas higher CYP7A1 activity was
      associated with the -203A allele in the patient group (C4/cholesterol ratio, 29.0
      vs. 14.8 microg/mmol, P = 0.032; C4/non-HDL-cholesterol ratio, 53.3 vs. 21.3
      microg/mmol in -203AA and -203CC, P = 0.017, respectively), no differences were
      observed in the healthy controls. We conclude that under physiological
      conditions, the -203A>C polymorphism in the CYP7A1 gene promoter region does not
      seem to have any clinically relevant effect. However, in patients with severe
      bile salt malabsorption, this polymorphism markedly affects CYP7A1 activity.

PMID- 18728291
TI  - How do you feel about...? Health outcomes in late life and self-perceptions of
      health and well-being.
AB  - Research has shown over the years that the self-perceptions of older adults about
      their health and well-being may be at least as important as objective data for
      predicting the course of their health over time. I review a series of studies
      that span 30 years in which I and my colleagues have asked older adults in the
      community about their self-rated health and well-being across a spectrum of
      parameters, including self-rated health, social support, and mood (both negative
      and positive), and about whether their basic needs are being met. The social
      environment shapes perceptions of health and well-being, as does the body.
      Feelings, such as feelings about health and well-being, are therefore a key (but
      not the only) psychological-behavioral bridge between the body (genome and
      physiology) and society (environmental stressors and social context). Following a
      review of these studies, I attempt to place these perceptions of health and well
      being in a social context, a context critical to understanding the consistency
      and strength of these studies (and others performed over many years) documenting
      the association between answers to the question "How do you feel about...?" and
      health outcomes over time.

PMID- 18728292
TI  - How can we make the pain go away? Public policies to manage pain at the end of
      life.
AB  - The continued undertreatment of pain at the end of life is a substantive public
      health problem that has not been resolved through increased public awareness, the
      issuance of clinical guidance for providers, or expanded organizational
      commitments. In this forum, we illuminate the role of public policies in
      promoting pain management. We review federal and state policies and consider
      empirical evaluations that compared the quality of state policies and the factors
      that contributed to their formation. We resolve that any organized interest in
      improving end-of-life care should begin by focusing on the development and
      expansion of those state policies that support the provision of evidence-based
      medicine for reducing the amount of pain an individual experiences at the end of
      life. Although empirical research is needed to determine which particular aspects
      of state pain policy are most critical and how these policies can be implemented
      most effectively, any organized effort that advances state medical board activity
      or another state policy would appear to be making an important step toward making
      the pain at the end of life go away.

PMID- 18728293
TI  - Medicare part D and the nursing home setting.
AB  - PURPOSE: The purpose of this article is to explore how the introduction of
      Medicare Part D is changing the operations of long-term-care pharmacies (LTCPs)
      and nursing homes, as well as implications of those changes for nursing home
      residents. DESIGN AND METHODS: We reviewed existing sources of information and
      interviewed stakeholders across various perspectives. We conducted 31
      semistructured telephone interviews with key stakeholders between November 2006
      and January 2007. RESULTS: Part D represents a substantial departure from how
      prescription drugs were previously financed and administered in nursing homes,
      and nursing home providers and LTCPs have struggled in adapting to some of these
      changes. Part D increased the variation around formularies and drug management
      processes for residents at the facility level, creating additional burden on
      clinical and pharmacy staff and introducing a tension between facilities' need to
      dispense medications quickly and assuring of coverage for those drugs. Nursing
      home and LTCP stakeholders perceive wide variation across Part D plans in their
      ability to meet the needs of nursing home residents. IMPLICATIONS: Although
      LTCPs, nursing homes and their clinicians, and Part D plans will gain experience
      with the benefit in the nursing home setting over time, stakeholders we
      interviewed identified a range of longer term issues and questions that merit
      attention as the benefit proceeds.

PMID- 18728294
TI  - Physical restraint initiation in nursing homes and subsequent resident health.
AB  - PURPOSE: It is widely believed that physical restraint use causes mental and
      physical health decline in nursing home residents. Yet few studies exist showing
      an association between restraint initiation and health decline. In this research,
      we examined whether physical restraint initiation is associated with subsequent
      lower physical or mental health. DESIGN AND METHODS: We used all nursing homes (N
      = 740) in Pennsylvania in 2001, with 12,820 residents. We used the Minimum Data
      Set data; Online Survey, Certification and Reporting data; and the Area Resource
      File as data sources. We restricted our sample to newly admitted nursing home
      residents who were not restrained in the first two quarters of their residency.
      We examined which facility and individual characteristics during those first two
      quarters were associated with restraint initiation during the third quarter. We
      then examined the association of third-quarter restraint initiation with fourth
      quarter health outcomes, using regressions that controlled for first- and second
      quarter health status as well as other resident, facility, and market
      characteristics. The physical health outcomes examined consisted of falls,
      walking dependence, activities of daily living (ADLs), pressure ulcers, and
      contractures. Mental health outcomes examined consisted of cognitive performance,
      depression, and behavior problems. RESULTS: The initiation of restraint use was
      associated with a previous fall (p <.01), psychoactive medication use (p <.05),
      low cognition (p <.01), ADL scores (p <.01), and the absence of pressure ulcers
      (p <.10), as well as a variety of facility characteristics. Subsequent to
      restraint initiation, we found an association with lower cognitive performance (p
      <.01), lower ADL performance (p <.01), and higher walking dependence (p <.01).
      IMPLICATIONS: We found that an association between restraint initiation and
      subsequent adverse health consequences exists and is substantial. Moreover, these
      results would appear to have practical as well as statistical significance.

PMID- 18728295
TI  - Nurse preparation and organizational support for supervision of unlicensed
      assistive personnel in nursing homes: a qualitative exploration.
AB  - PURPOSE: Nursing supervision of the routine daily care (e.g., grooming, feeding,
      and toileting) that is delegated to unlicensed assistive personnel (UAP) is
      critical to nursing home service delivery. The conditions under which the
      supervisory role is organized and operationalized at the work-unit level, taking
      into account workloads, registered nurse/licensed practical nurse staffing, and
      role expectations, are not well understood. The purpose of this paper is to
      describe the organizational, managerial, and nurse-level factors associated with
      the nurse's role as supervisor of UAP in nursing homes. DESIGN AND METHODS: An
      ethnographic approach to data collection included 31 interviews, 170 hr of
      observation, and organizational document review at three nursing homes. Analysis
      included micro-coding and content analysis. RESULTS: Findings revealed (a)
      considerable variation in organizational resources, systems, and processes to
      support organization and operationalization of the supervisory role; and (b)
      limited evidence of nurses' estimation of the potential benefits of training and
      organizational systems to support supervisory practice and the complexity of the
      supervisory role. IMPLICATIONS: Delivery of high-quality nursing home care is a
      matter of national importance, and these findings offer a call to action for
      nursing home leaders in policy, academia, and ownership and management positions.
      Nurses must be equipped with competencies and skills that reflect the complex
      organizational environments in which they work. Additionally, nursing home
      administrators and managers must be equipped with the competencies and skills
      needed to effectively and efficiently organize and operationalize care delivery
      practices to support nurses' role enactment.

PMID- 18728296
TI  - Further examination of the influence of caregiver staffing levels on nursing home
      quality.
AB  - PURPOSE: Weak empirical evidence exists showing that nursing home staffing levels
      influence quality of care. We propose that weak findings have resulted in many
      prior analyses because research models have underspecified the labor composition
      needed to influence care processes that, in turn, influence quality of care. In
      this analysis, we specified the nursing home labor composition by using staff
      stability, use of agency staff, and professional staff mix, in addition to
      staffing levels. DESIGN AND METHODS: Data used in this investigation came from
      surveys of nursing home administrators (N = 6,005); Nursing Home Compare; the
      Online Survey, Certification and Reporting data; and the Area Resource File.
      Staffing characteristics, quality indicators, facility, and market information
      from these data sources were all measured in 2004. RESULTS: The regression
      analyses showed that staffing levels alone were weakly associated with the six
      quality measures examined. However, when the regression models were more fully
      specified (by including agency staff, stability, and professional staff mix),
      staffing levels were generally associated with the quality measures (i.e., 15 of
      the 18 staffing coefficients were significant). IMPLICATIONS: Simply adding more
      staff may be a necessary but not sufficient means of improving nursing home
      quality. Some accounting for agency staff, stability, and professional staff mix
      is also needed.

PMID- 18728297
TI  - Referral and timing of referral to hospice care in nursing homes: the significant
      role of staff members.
AB  - PURPOSE: Given concerns about end-of-life care for many nursing home (NH)
      residents, this study sought to understand factors influencing hospice referral
      or nonreferral as well as timing of referral. DESIGN AND METHODS: We conducted
      semistructured interviews with personnel from seven participating NHs and two
      hospices. We interviewed NH directors of nursing regarding facility referral
      practices and conducted interviews with 34 NH nurses, 30 NH aides, and 17 hospice
      nurses knowledgeable about the factors that led to the hospice status of 32 NH
      decedents. Selected decedents varied by diagnosis and hospice status (received
      hospice for >7 days, <or=7 days, or not at all). We audiotaped, transcribed, and
      coded interviews for themes. RESULTS: NH staff members' recognition of terminal
      decline, beliefs about hospice, and initiative significantly influenced hospice
      referral and timing of referral. Staff members' recognition of familiar signs of
      decline facilitated hospice referral; in contrast, a perception that death was
      unexpected impeded referral, and a perception of uncertain prognosis delayed
      referral. Staff members' beliefs that hospice does not add value to NH care or is
      for crises only impeded referral, and a belief that hospice is only for the "very
      end" delayed referral. Residents received hospice for longer periods when staff
      believed that hospice complemented NH care and when staff took the initiative in
      raising the option of hospice. IMPLICATIONS: Enhanced training about recognizing
      terminal decline, hospice services in NHs, and the role of staff initiative would
      support NH staff in raising the option of hospice when appropriate.

PMID- 18728298
TI  - The end-of-life experience in long-term care: five themes identified from focus
      groups with residents, family members, and staff.
AB  - PURPOSE: We designed this study to examine the end-of-life (EOL) experience in
      long-term care (LTC) based on input from key stakeholders. DESIGN AND METHODS:
      The study consisted of 10 homogeneous focus groups drawn from a purposive sample
      of LTC residents (2 groups; total n = 11), family caregivers (2 groups; total n =
      19), paraprofessional staff (3 groups; total n = 20), and licensed/registered
      staff (3 groups; total n = 15) from five nursing homes and eight residential
      care/assisted living communities in North Carolina. We analyzed data by using
      grounded theory techniques to elicit manifest and latent themes. RESULTS: Five
      overarching themes emerged: (a) components of a good death in LTC, (b) normalcy
      of dying in LTC, (c) the role of relationships in the provision and receipt of
      care, (d) hospice contributions to care at the EOL in LTC, and (e) stakeholder
      recommendations for enhancing EOL care in these settings. Underlying these themes
      was one central category, closeness, based on physical proximity and frequency of
      contact. IMPLICATIONS: Findings suggest that promoting collaborative
      relationships among the four stakeholder groups, increasing social worker
      involvement, and removing barriers to hospice may enhance the EOL experience in
      LTC.

PMID- 18728299
TI  - Postdischarge environmental and socioeconomic factors and the likelihood of early
      hospital readmission among community-dwelling Medicare beneficiaries.
AB  - PURPOSE: This study attempts to determine the associations between postdischarge
      environmental (PDE) and socioeconomic (SES) factors and early readmission to
      hospitals. DESIGN AND METHODS: This study was a cohort study using the 2001
      Medicare Current Beneficiary Survey and Medicare claims for the period from 2001
      to 2002. The participants were community-dwelling Medicare beneficiaries admitted
      to hospitals, discharged home, and surviving at least 1 year after discharge (n =
      1,351). The study measurements were early readmission (within 60 days), PDE
      factors, and SES factors. PDE factors consisted of having a usual source of care,
      requiring assistance to see the usual source of care, marital status, living
      alone, lacking self-management skills, having unmet functional need, having no
      helpers with activities of daily living, number of living children, and number of
      levels in the home. SES factors consisted of education, income, and Medicaid
      enrollment. RESULTS: Of the 1,351 beneficiaries, 202 (15.0%) experienced an early
      readmission. After adjustment for demographics, health, and functional status,
      the odds of early readmission were increased by living alone (odds ratio or OR =
      1.50, 95% confidence interval or CI = 1.01-2.24), having unmet functional need
      (OR = 1.48, 95% CI = 1.04-2.10), lacking self-management skills (OR = 1.44, 95%
      CI = 1.03-2.02), and having limited education (OR = 1.42, 95% CI = 1.01-2.02).
      IMPLICATIONS: These findings suggest that PDE and SES factors are associated with
      early readmission. Considering these findings may enhance the targeting of pre
      discharge and postdischarge interventions to avert early readmission. Such
      interventions may include home health services, patient activation, and
      comprehensive discharge planning.

PMID- 18728300
TI  - Relationship between perceived needs and assessed needs for services in community
      dwelling older persons.
AB  - PURPOSE: We examine the relationship between the perceived needs and assessed
      needs of community-dwelling seniors. DESIGN AND METHODS: Trained research
      assistants administered the Naturally Occurring Retirement Community Baseline
      Survey to 268 community-dwelling older adults in suburban Maryland. Perceived and
      assessed needs were measured in the domains of health and function (memory,
      health, functional needs, mobility, and financial management), mental health
      (depression and loneliness), sensory functioning (vision), and health behaviors
      (nutrition and exercise). RESULTS: In the areas of functional needs, mobility,
      financial management, loneliness, and vision, persons who scored as more needy
      were already utilizing significantly more services. Of persons not receiving
      services, participants in need of memory, physical health, functional,
      loneliness, and nutrition services were more likely to indicate they would use
      those services. Although there were significant relationships between assessed
      needs and perceived needs, there was also a high level of discrepancy, such that
      a substantial proportion of those participants screened as not needing services
      requested those services, and a sizable proportion of those who screened as
      needing services did not request them. The results also show a high prevalence of
      needs among older adults and yet low service use by those with needs for these
      services. IMPLICATIONS: Both assessed and perceived needs should be examined in
      future need assessment surveys. Further investigations into the nature of
      discrepancies will likely result in improvement in the methodologies of screening
      assessed and perceived needs. Services targeted to older adults must be made more
      available to those dwelling in the community.

PMID- 18728301
TI  - An ethnographic study of stigma and ageism in residential care or assisted
      living.
AB  - PURPOSE: This study explored aspects of stigmatization for older adults who live
      in residential care or assisted living (RC-AL) communities and what these
      settings have done to address stigma. DESIGN AND METHODS: We used ethnography and
      other qualitative data-gathering and analytic techniques to gather data from 309
      participants (residents, family and staff) from six RC-AL settings in Maryland.
      We entered the transcript data into Atlas.ti 5.0. We analyzed the data by using
      grounded theory techniques for emergent themes. RESULTS: Four themes emerged that
      relate to stigma in RC-AL: (a) ageism in long-term care; (b) stigma as related to
      disease and illness; (c) sociocultural aspects of stigma; and (d) RC-AL as a
      stigmatizing setting. Some strategies used in RC-AL settings to combat stigma
      include family member advocacy on behalf of stigmatized residents, assertion of
      resident autonomy, and administrator awareness of potential stigmatization.
      IMPLICATIONS: Findings suggest that changes could be made to the structure as
      well as the process of care delivery to minimize the occurrence of stigma in RC
      AL settings. Structural changes include an examination of how best, given the
      resident case mix, to accommodate care for persons with dementia (e.g., separate
      units or integrated care); processes of care include staff recognition of
      resident preferences and strengths, rather than their limitations.

PMID- 18728302
TI  - Creating grander families: older adults adopting younger kin and nonkin.
AB  - PURPOSE: There is a dearth of research on older adoptive parents caring for minor
      children, despite a growing number of such adoptions finalized each year. This
      study offers a large-scale investigation of adoptive families headed by older
      parents. We describe these families and explore how preadoptive kinship between
      the adoptive parent and the child impacts adoption outcomes. DESIGN AND METHODS:
      We analyze data from kin (n = 98) and nonkin (n = 310) adoptive families headed
      by adults aged 60 years and older. RESULTS: We find that older kin adoptive
      families are smaller, report lower income, and include adoptive mothers with less
      formal education. Children in these families had less severe needs for special
      care at the time of placement. Although kin and nonkin older parents offer
      similar assessments of their parent-child relationships, kin adopters indicate a
      greater willingness to adopt the same child again and yet report less positive
      current family functioning. Multivariate regression analyses reveal that
      preadoptive kinship predicts more negative parental assessment of the adoption's
      impact on the family and less positive family functioning net of other parent,
      family, and child characteristics. Externalizing behavior by the child (e.g.,
      delinquency or aggression) is the strongest predictor of deleterious outcomes for
      both groups. IMPLICATIONS: Kin adoption by older adults creates new families
      under strain but does not reduce parental commitment to the child. We conclude
      that older adults serve as effective adoptive parents but would benefit from
      preadoption and postadoption services to assist them in preparing for and
      positively addressing the challenging behaviors exhibited by adopted children.

PMID- 18728303
TI  - Hazards of hospitalization: residence prior to admission predicts outcomes.
AB  - PURPOSE: Previous studies investigating adverse outcomes of hospitalized elders
      have focused on community-dwelling patients. Given the rapid growth of
      populations living in other settings, such as assisted living facilities, it is
      important to understand whether these patients are at higher risk of experiencing
      specific adverse outcomes during hospitalization, so that interventions can be
      developed to reduce risk. METHODS: This is a prospective, observational study of
      212 sequential patients admitted during a 1-month period in 2006 to a 38-bed
      Acute Care for Elders unit in Rochester, New York and followed until discharge.
      We categorized the patients by residence prior to admission (i.e., community,
      assisted living, and nursing home). Our outcome categories were: worsening
      function, delirium, depression, falls, pressure sores, and nursing home
      admission. RESULTS: After adjusting for multiple characteristics, we found that
      patients admitted from assisted living facilities were at substantially higher
      risk than those admitted from the community for functional decline and falls.
      Patients from nursing homes had a trend toward increased risk for these outcomes,
      but the trend did not reach statistical significance. More than three fourths of
      assisted living facility residents were discharged to a nursing home after
      hospitalization, with a relative risk of 9.41 (p <.001) versus community-dwellers
      for this outcome. IMPLICATIONS: People who are admitted to the hospital from
      assisted living facilities are at high risk for falls and functional decline
      during hospitalization. Assisted living residents are at a particularly high risk
      of nursing home admission following hospitalization. Targeted preventive programs
      should be developed with a goal of reducing risk in this vulnerable population.

PMID- 18728304
TI  - Project ADAPT: a program to assess depression and provide proactive treatment in
      rural areas.
AB  - PURPOSE: We describe and evaluate a project designed to pilot test an evidence
      based clinical intervention for assessing and treating depression in older adults
      in rural primary care clinics. Project ADAPT-Assuring Depression Assessment and
      Proactive Treatment-utilized existing primary care resources to overcome barriers
      to sustainability experienced by similar projects. DESIGN AND METHODS: This
      multifaceted intervention, which was structured after the successful IMPACT
      (Improving Mood/Promoting Access to Collaborative Treatment) research
      intervention, used on-site geriatric depression specialists, clinic staff
      training, team collaboration, and depression practice guidelines to improve
      depression care for rural elders. IMPACT screening and assessment instruments and
      treatment protocols were modified for use by less highly trained staff already
      employed by the rural primary care clinics. Patient and provider depression
      educational materials and depression screening and monitoring protocols were
      provided by means of regional training sessions and phone contact. Evaluation
      data were collected by mail and phone surveys. RESULTS: Although Project ADAPT
      materials and training were initially developed for providers in rural primary
      care clinics, most participants came from long-term-care facilities, hospitals,
      home care, and public health and social service agencies. Forty-four sites sent
      56 staff to Project ADAPT regional trainings, but many did not participate after
      the initial training. Participants who did continue reported that training
      improved geriatric depression screening and communication with the primary
      provider. IMPLICATIONS: Outcomes suggest that provider, patient, and system
      issues have to be addressed differently in rural areas to improve geriatric
      depression treatment in primary care settings.

PMID- 18728307
TI  - A new way of adapting IMRT delivery fraction-by-fraction to cater for variable
      intrafraction motion.
AB  - In this paper a technique is presented for adaptive therapy to compensate for
      variable intrafraction tissue motion. So long as the motion can be measured or
      deduced for each fraction the technique modifies the fluence profile for the
      subsequent fractions in a repeatable cyclic way. The fluence modification is
      based on projecting the dose discrepancies between the cumulative delivered dose
      after each fraction and the expected planned dose at the same stage. It was shown
      that, in general, it is best to adapt the fluence profile to moving leaves that
      also have been modified to 'breathe' according to some regular default motion.
      However, it is important to point out that, if this regular default motion were
      to differ too much from the variable motion at each fraction, then the result can
      be worse than adapting to non-breathing leaves in a dynamic MLC technique.
      Furthermore, in general it should always be possible to improve results by
      starting the adaptation process with a constrained deconvolution of the regular
      default motion.

PMID- 18728306
TI  - Defining drug targets in yeast haploinsufficiency screens: application to human
      translational pharmacology.
AB  - A major challenge in drug discovery is to identify the cellular targets
      responsible for the pharmacological activity of drug candidates. In the yeast
      Saccharomyces cerevisiae, a heterozygous diploid mutant collection of
      approximately 6000 strains, in each of which one copy of a single gene is
      deleted, is commercially available. With this collection, it is possible to
      evaluate the role of each gene product in the response of cells to a drug. Drug
      induced haploinsufficiency refers to the situation where a heterozygous diploid
      mutant is more sensitive to a drug than is the wild-type strain. Drug-induced
      haploinsufficiency screening has the potential to reveal pharmacological targets
      of drugs and those that contribute to undesired side effects, as well as gene
      products involved in drug transport, metabolism, or resistance. Using published
      studies, I present advantages and limitations of this technique and discuss its
      value for predicting drug targets in human cells.

PMID- 18728305
TI  - Application of fluorescence resonance energy transfer and magnetic twisting
      cytometry to quantify mechanochemical signaling activities in a living cell.
AB  - Mechanotransduction is the process by which living cells sense mechanical forces
      and then convert them into biochemical signaling. Recently, we showed that
      mechanical stress is transduced from the cell surface to remote cytoplasmic sites
      within 0.3 seconds, which is at least 40 to 50 times faster than soluble factor
      induced signal transduction, and the sites of mechanotransduction colocalize with
      mechanical stress-induced microtubule displacements. These results suggest that
      mechanotransduction employs mechanisms different from those of soluble factor
      induced signal transduction. Here, we describe a protocol that utilizes
      fluorescence resonance energy transfer (FRET) and a magnetic twisting cytometry
      (MTC) device to capture rapid mechanochemical signaling activities in living
      cells.

PMID- 18728308
TI  - FDTD analysis of body-core temperature elevation in children and adults for whole
      body exposure.
AB  - The temperature elevations in anatomically based human phantoms of an adult and a
      3-year-old child were calculated for radio-frequency whole-body exposure.
      Thermoregulation in children, however, has not yet been clarified. In the present
      study, we developed a computational thermal model of a child that is reasonable
      for simulating body-core temperature elevation. Comparison of measured and
      simulated temperatures revealed thermoregulation in children to be similar to
      that of adults. Based on this finding, we calculated the body-core temperature
      elevation in a 3-year-old child and an adult for plane-wave exposure at the basic
      restriction in the international guidelines. The body-core temperature elevation
      in the 3-year-old child phantom was 0.03 degrees C at a whole-body-averaged
      specific absorption rate of 0.08 W kg(-1), which was 35% smaller than in the
      adult female. This difference is attributed to the child's higher body surface
      area-to-mass ratio.

PMID- 18728309
TI  - Effects of radiation quality on the calibration of kerma-area product meters in x
      ray beams.
AB  - The calibration coefficients of kerma-area product meters significantly depend on
      the energy spectrum of the x-ray beam. This effect was examined by measuring the
      calibration coefficients for several radiation qualities in the range generally
      used in diagnostic x-ray imaging. The intention was to determine the calibration
      coefficients for other radiation qualities by interpolation between the measured
      values, relative to one or more suitable parameters. The x-ray tube voltage,
      total filtration and half-value thickness were examined as possible specifiers of
      the energy distribution. No single parameter provided an interpolation of
      calibration coefficients with the accuracy recommended by the ICRU and IAEA,
      except for a narrow range of radiation qualities. At least two of the parameters
      are needed to reliably specify the radiation quality for the interpolation of
      calibration coefficients.

PMID- 18728310
TI  - Clinical ultraviolet dosimetry with a CCD monochromator array spectroradiometer.
AB  - Single monochromator charge-coupled device (CCD) array spectroradiometers have
      the advantage of ease of use and speed compared with double grating instruments.
      Their inherently inferior stray-light rejection, however, can critically affect
      their accuracy in phototherapy and research-related dosimetry applications. This
      paper shows that without adequate correction the HR4000 (Ocean Optics Inc.,
      Dunedin, USA) array device can overestimate the CIE erythema-weighted irradiance
      of common phototherapy sources and solar simulator beams by over 100%. A software
      stray-light correction (Ylianttila et al 2005 Photochem. Photobiol. 81 333-41),
      using the measured slit function of the HR4000, has been applied to spectra
      acquired from sources used in phototherapy and photobiology (PUVA, UV21, TL01 and
      solar simulator). The resulting corrected erythema-weighted irradiance
      measurements from the HR4000 are within 10% of those from a DM150 double grating
      spectroradiometer (Bentham Instruments Ltd, Reading, UK). A simple model is
      considered for combining estimates of measurement uncertainties. The importance
      of exposure bracketing to improve the dynamic range of the HR4000 is illustrated,
      along with the difficulty in making direct comparison of spectral values between
      two instruments due to wavelength scale uncertainties. Comparison with a double
      grating instrument in a solar simulator beam is examined here as a basis for
      validating CCD array device measurements. The study demonstrates that the HR4000
      array spectroradiometer can provide an adequate level of accuracy for common
      phototherapy and photobiology applications only where a suitable stray-light
      correction is carefully applied and where the instrument's effective dynamic
      range is improved.

PMID- 18728311
TI  - Process control analysis of IMRT QA: implications for clinical trials.
AB  - The purpose of this study is two-fold: first is to investigate the process of
      IMRT QA using control charts and second is to compare control chart limits to
      limits calculated using the standard deviation (sigma). Head and neck and
      prostate IMRT QA cases from seven institutions in both academic and community
      settings are considered. The percent difference between the point dose
      measurement in phantom and the corresponding result from the treatment planning
      system (TPS) is used for analysis. The average of the percent difference
      calculations defines the accuracy of the process and is called the process
      target. This represents the degree to which the process meets the clinical goal
      of 0% difference between the measurements and TPS. IMRT QA process ability
      defines the ability of the process to meet clinical specifications (e.g. 5%
      difference between the measurement and TPS). The process ability is defined in
      two ways: (1) the half-width of the control chart limits, and (2) the half-width
      of +/-3sigma limits. Process performance is characterized as being in one of four
      possible states that describes the stability of the process and its ability to
      meet clinical specifications. For the head and neck cases, the average process
      target across institutions was 0.3% (range: -1.5% to 2.9%). The average process
      ability using control chart limits was 7.2% (range: 5.3% to 9.8%) compared to
      6.7% (range: 5.3% to 8.2%) using standard deviation limits. For the prostate
      cases, the average process target across the institutions was 0.2% (range: -1.8%
      to 1.4%). The average process ability using control chart limits was 4.4% (range:
      1.3% to 9.4%) compared to 5.3% (range: 2.3% to 9.8%) using standard deviation
      limits. Using the standard deviation to characterize IMRT QA process performance
      resulted in processes being preferentially placed in one of the four states. This
      is in contrast to using control charts for process characterization where the
      IMRT QA processes were spread over three of the four states with none of the
      processes in the ideal state. Control charts may be used for IMRT QA in clinical
      trials to categorize process performance, minimize protocol variation and guide
      process improvements. For the duration of an institution's participation in a
      protocol, updated control charts can be periodically sent to the protocol QA
      center to document continued process performance to protocol specifications.

PMID- 18728312
TI  - A twelve-analyzer detector system for high-resolution powder diffraction.
AB  - A dedicated high-resolution high-throughput X-ray powder diffraction beamline has
      been constructed at the Advanced Photon Source (APS). In order to achieve the
      goals of both high resolution and high throughput in a powder instrument, a multi
      analyzer detector system is required. The design and performance of the 12
      analyzer detector system installed on the powder diffractometer at the 11-BM
      beamline of APS are presented.

PMID- 18728313
TI  - On-line optical and X-ray spectroscopies with crystallography: an integrated
      approach for determining metalloprotein structures in functionally well defined
      states.
AB  - X-ray-induced redox changes can lead to incorrect assignments of the functional
      states of metals in metalloprotein crystals. The need for on-line monitoring of
      the status of metal ions (and other chromophores) during protein crystallography
      experiments is of growing importance with the use of intense synchrotron X-ray
      beams. Significant efforts are therefore being made worldwide to combine
      different spectroscopies in parallel with X-ray crystallographic data collection.
      Here the implementation and utilization of optical and X-ray absorption
      spectroscopies on the modern macromolecular crystallography (MX) beamline 10, at
      the SRS, Daresbury Laboratory, is described. This beamline is equipped with a
      dedicated monolithic energy-dispersive X-ray fluorescence detector, allowing X
      ray absorption spectroscopy (XAS) measurements to be made in situ on the same
      crystal used to record the diffraction data. In addition, an optical
      microspectrophotometer has been incorporated on the beamline, thus facilitating
      combined MX, XAS and optical spectroscopic measurements. By uniting these
      techniques it is also possible to monitor the status of optically active and
      optically silent metal centres present in a crystal at the same time. This unique
      capability has been applied to observe the results of crystallographic data
      collection on crystals of nitrite reductase from Alcaligenes xylosoxidans, which
      contains both type-1 and type-2 Cu centres. It is found that the type-1 Cu centre
      photoreduces quickly, resulting in the loss of the 595 nm peak in the optical
      spectrum, while the type-2 Cu centre remains in the oxidized state over a much
      longer time period, for which independent confirmation is provided by XAS data as
      this centre has an optical spectrum which is barely detectable using
      microspectrophotometry. This example clearly demonstrates the importance of using
      two on-line methods, spectroscopy and XAS, for identifying well defined redox
      states of metalloproteins during crystallographic data collection.

PMID- 18728314
TI  - Disentanglement of magnetic contributions in multi-component systems by using X
      ray magnetic circular dichroism at a single absorption edge.
AB  - X-ray magnetic circular dichroism (XMCD) has become in recent years an
      outstanding tool for studying magnetism. Its element specificity, inherent to
      core-level spectroscopy, combined with the application of magneto-optical sum
      rules allows quantitative magnetic measurements at the atomic level. These
      capabilities are now incorporated as a standard tool for studying the localized
      magnetism in many systems. However, the application of XMCD to the study of the
      conduction-band magnetism is not so straightforward. Here, it is shown that the
      atomic selectivity is not lost when XMCD probes the delocalized states. On the
      contrary, it provides a direct way of disentangling the magnetic contributions to
      the conduction band coming from the different elements in the material. This is
      demonstrated by monitoring the temperature dependence of the XMCD spectra
      recorded at the rare-earth L(2)-edge in the case of RT(2) (R = rare-earth, T = 3d
      transition metal) materials. These results open the possibility of performing
      element-specific magnetometry by using a single X-ray absorption edge.

PMID- 18728315
TI  - Application of a pnCCD in X-ray diffraction: a three-dimensional X-ray detector.
AB  - The first application of a pnCCD detector for X-ray scattering experiments using
      white synchrotron radiation at BESSY II is presented. A Cd arachidate multilayer
      was investigated in reflection geometry within the energy range 7 keV < E < 35
      keV. At fixed angle of incidence the two-dimensional diffraction pattern
      containing several multilayer Bragg peaks and respective diffuse-resonant Bragg
      sheets were observed. Since every pixel of the detector is able to determine the
      energy of every incoming photon with a resolution DeltaE/E approximately 10(-2),
      a three-dimensional dataset is finally obtained. In order to achieve this energy
      resolution the detector was operated in the so-called single-photon-counting
      mode. A full dataset was evaluated taking into account all photons recorded
      within 10(5) detector frames at a readout rate of 200 Hz. By representing the
      data in reciprocal-space coordinates, it becomes obvious that this experiment
      with the pnCCD detector provides the same information as that obtained by
      combining a large number of monochromatic scattering experiments using
      conventional area detectors.

PMID- 18728316
TI  - The optimum conditions to collect X-ray data from very small samples.
AB  - A previous paper [Nave & Hill (2005). J. Synchrotron Rad. 12, 299-303] examined
      the possibility of reduced radiation damage for small crystals (10 microm and
      below in size) under conditions where the photoelectrons could escape from the
      sample. The conclusion of this paper was that higher-energy radiation (e.g. 40
      keV) could offer an advantage as the photoelectron path length was greater and
      less energy would be deposited in the crystal. This paper refines these
      calculations further by including the effects of energy deposited owing to
      Compton scattering and the energy difference between the incident photon and the
      emitted photoelectron. An estimate is given for the optimum wavelength for
      collecting data from a protein crystal of a given size and composition. Another
      way of reducing radiation damage from a protein crystal is to collect data with a
      very short pulsed X-ray source where a single image can be obtained before
      subsequent radiation damage occurs. A comparison of this approach compared with
      the use of shorter wavelengths is made.

PMID- 18728317
TI  - Classification of Fe-bearing species from K-edge XANES data using two-parameter
      correlation plots.
AB  - Solid iron compounds are extremely common in the environment as well as in
      meteorites and comets. Fe K-edge XANES (X-ray absorption near-edge structure)
      measurements can be carried out quickly, theoretically allowing one to categorize
      many areas within a sample or set of samples in a short time. However,
      interpretation of such data is not straightforward unless one has the appropriate
      reference spectra, hence a way of classifying an unknown spectrum to a family
      group (trivalent, divalent, oxide, silicate etc.) is required. Methods of
      abstracting Fe XANES spectra to produce pairs of variables which, when plotted,
      cluster in distinct regions depending on the family are presented. For instance,
      divalent minerals fall in a different region than trivalent minerals, and
      sulfides in a different region than oxides.

PMID- 18728318
TI  - Polarization analysis in soft X-ray diffraction to study magnetic and orbital
      ordering.
AB  - An experimental approach to the analysis of charge, magnetic and orbital ordering
      in 3d transition-metal oxides is presented. The technique combines two important
      components: azimuthal rotations around the Bragg wavevector and polarization
      analysis of the Bragg intensities in the range 500-900 eV. The polarization
      analysis is performed using graded multilayers, which are translated and rotated
      in the vacuum chamber. It is shown why these two components are important to
      determine the origin of the Bragg scattered signals and how they allow us to
      separate the different contributions. Examples are given for the oxygen K and the
      Mn, Co, Ni and Cu L(2,3)-edges, and the advantages and drawbacks of this
      experimental technique are discussed.

PMID- 18728319
TI  - Synchrotron applications of an amorphous silicon flat-panel detector.
AB  - A GE Revolution 41RT flat-panel detector (GE 41RT) from GE Healthcare (GE) has
      been in operation at the Advanced Photon Source for over two years. The detector
      has an active area of 41 cm x 41 cm with 200 microm x 200 microm pixel size. The
      nominal working photon energy is around 80 keV. The physical set-up and utility
      software of the detector system are discussed in this article. The linearity of
      the detector response was measured at 80.7 keV. The memory effect of the detector
      element, called lag, was also measured at different exposure times and gain
      settings. The modulation transfer function was measured in terms of the line
      spread function using a 25 microm x 1 cm tungsten slit. The background (dark)
      signal, the signal that the detector will carry without exposure to X-rays, was
      measured at three different gain settings and with exposure times of 1 ms to 15
      s. The radial geometric flatness of the sensor panel was measured using the
      diffraction pattern from a CeO(2) powder standard. The large active area and fast
      data-capturing rate, i.e. 8 frames s(-1) in radiography mode, 30 frames s(-1) in
      fluoroscopy mode, make the GE 41RT one of a kind and very versatile in
      synchrotron diffraction. The loading behavior of a Cu/Nb multilayer material is
      used to demonstrate the use of the detector in a strain-stress experiment. Data
      from the measurement of various samples, amorphous SiO(2) in particular, are
      presented to show the detector effectiveness in pair distribution function
      measurements.

PMID- 18728320
TI  - A high-temperature furnace for in situ synchrotron X-ray spectroscopy under
      controlled atmospheric conditions.
AB  - A high-temperature furnace with an induction heater coil has been designed and
      constructed for in situ X-ray spectroscopic experiments under controlled
      atmospheric conditions and temperatures up to 3275 K. The multi-purpose chamber
      design allows working in backscattering and normal fluorescence mode for
      synchrotron X-ray absorption and emission spectroscopy. The use of the furnace is
      demonstrated in a study of the in situ formation of Cr oxide between 1823 K and
      2023 K at logPO(2) values between -10.0 and -11.3 using X-ray absorption near
      edge spectroscopy. The set-up is of particular interest for studying liquid
      metals, alloys and other electrically conductive materials under extreme
      conditions.

PMID- 18728321
TI  - Diffraction of X-ray free-electron laser femtosecond pulses on single crystals in
      the Bragg and Laue geometry.
AB  - A solution of the problem of dynamical diffraction for X-ray pulses with
      arbitrary dimensions in the Bragg and Laue cases in a crystal of any thickness
      and asymmetry coefficient of reflection is presented. Analysis of pulse form and
      duration transformation in the process of diffraction and propagation in a vacuum
      is conducted. It is shown that only the symmetrical Bragg case can be used to
      avoid smearing of reflected pulses.

PMID- 18728322
TI  - Very first tests on SOLEIL regarding the Zn environment in pathological
      calcifications made of apatite determined by X-ray absorption spectroscopy.
AB  - This very first report of an X-ray absorption spectroscopy experiment at
      Synchrotron SOLEIL is part of a long-term study dedicated to pathological
      calcifications. Such biological entities composed of various inorganic and/or
      organic compounds also contain trace elements. In the case of urinary calculi,
      different papers already published have pointed out that these oligo-elements may
      promote or inhibit crystal nucleation as well as growth of mineral. Use of this
      analytical tool specific to synchrotron radiation, allowing the determination of
      the local environment of oligo-elements and thus their occupation site,
      contributes to the understanding of the role of trace elements in pathological
      calcifications.

PMID- 18728323
TI  - Structural analysis of sulfur in natural rubber using X-ray absorption near-edge
      spectroscopy.
AB  - X-ray absorption near-edge spectroscopy (XANES) has been applied to natural
      rubber in order to study the local environment of sulfur atoms in sulfur
      crosslinking structures introduced in the vulcanization process. Different types
      of chemical accelerators in conventional, semi-efficient and efficient
      vulcanization systems were investigated. The experimental results show the good
      sensitivity and reproducibility of XANES to characterize the local geometry and
      electronic environment of the sulfur K-shell under various conditions of
      vulcanization and non-vulcanization of natural rubber. Several applications of
      XANES in this study demonstrate an alternative way of identifying sulfur
      crosslinks in treated natural rubber based on differences in their spectra and
      oxidation states.

PMID- 18728324
TI  - On the Einstein model for EXAFS parallel and perpendicular mean-square relative
      displacements.
AB  - The correlated Einstein model for EXAFS parallel and perpendicular mean-square
      relative displacements (MSRDs) is discussed. By means of dynamical simulations on
      different crystalline structures, the error owing to the Einstein-fit model on
      the EXAFS MSRDs is estimated as a function of the standard deviation of the
      density of vibrational states. This error should be taken into account to improve
      the accuracy of the MSRDs.

PMID- 18728325
TI  - Bond cutting in K-doped tris(8-hydroxyquinoline) aluminium.
AB  - A series of Al 2p, K 2p, O 1s and N 1s core-level spectra have been used to
      characterize the interaction between potassium (K) and tris(8-hydroxyquinoline)
      aluminium (Alq(3)) molecules in the K-doped Alq(3) layer. All core-level spectra
      were tuned to be very surface sensitive in selecting various photon energies
      provided by the wide-range beamline at the National Synchrotron Radiation
      Research Center, Taiwan. A critical K concentration (x = 2.4) exists in the K
      doped Alq(3) layer, below which the K-doped atoms generate a strained environment
      near the O and N atoms within 8-quinolinoline ligands. This creates new O 1s and
      N 1s components on the lower binding-energy side. Above the critical K coverage,
      the K-doped atoms attach the O atoms in the Al-O-C bonds next to the phenoxide
      ring and replace Al-O-C bonds by forming K-O-C bonds. An Alq(3) molecule is
      disassembled into Alq(2) and Kq by bond cutting and bond formation. The Alq(2)
      molecule can be further dissociated into Alq, or even Al, through subsequent
      formations of Kq.

PMID- 18728326
TI  - Analyser-based tomography images of cartilage.
AB  - Analyser-based imaging expands the performance of X-ray imaging by utilizing not
      only the absorption properties of X-rays but also the refraction and scatter
      rejection (extinction) properties. In this study, analyser-based computed
      tomography has been implemented on imaging an articular cartilage sample,
      depicting substructural variations, without overlay, at a pixel resolution of 3.6
      microm.

PMID- 18728327
TI  - Visualization of age-dependent myocardial metabolic impairment in cardiomyopathic
      model hamster obtained by fluorescent X-ray computed tomography using I-127
      BMIPP.
AB  - Fluorescent X-ray computed tomography (FXCT) enables visualization of myocardial
      fatty acid metabolism by using non-radio-iodinated I-5-(p-iodophenyl)-3-(R,S)
      methylpentadecanoice acid (BMIPP). In this experiment, age-dependent myocardial
      metabolic impairment was successfully imaged and analyzed quantitatively in J2N-k
      cardiomyopathic hamster using FXCT.

PMID- 18728328
TI  - Calibration method at the N K-edge using interstitial nitrogen gas in solid-state
      nitrogen-containing inorganic compounds.
AB  - The standard method of soft X-ray beamline calibration at the N K-edge uses the
      nu = 0 peak transition of gas-phase N(2). Interstitial N(2) gas trapped or formed
      within widely available solid-state ammonium- and amine-containing salts can be
      used for this purpose, bypassing gas-phase measurements. Evidence from non
      nitrogen-containing compounds (KH(2)PO(4)) and from He-purged ammonium salts
      suggest that production of N(2) gas is through beam-induced decomposition.
      Compounds with nitrate or nitrite as anions produce coincident features and are
      not suitable for this calibration method.

PMID- 18728329
TI  - SaxsMDView: a three-dimensional graphics program for displaying force vectors.
AB  - A new three-dimensional graphics program, SaxsMDView, is described. The program
      performs a three-dimensional graphical representation for protein molecules along
      with the force vector (or vector potential) applying to each atom. The displayed
      object can be rotated and translated in arbitrary directions by interactive mouse
      manipulation. While SaxsMDView was originally intended to visualize the result of
      SAXS_MD, a previously developed program based on the restrained molecular
      dynamics with small-angle X-ray scattering constraints, it can also be useful for
      graphical representation of other objects such as coarse-grained molecular models
      reconstructed by ab initio modelling or solvent site-dipole field vectors induced
      around the protein molecule. Some examples of the application of the program
      including the graphical analyses of the results with SAXS_MD are also presented.

PMID- 18728332
TI  - Right ventricular remodeling and dysfunction with subsequent annular dilatation
      and tethering as a mechanism of isolated tricuspid regurgitation.
AB  - BACKGROUND: Secondary tricuspid regurgitation (TR) as a result of pulmonary
      hypertension and/or left-sided heart disease is caused by tricuspid valve (TV)
      annular dilatation and tethering of the tricuspid leaflet after right ventricular
      (RV) dilatation. However, the mechanism of isolated TR without significant
      pulmonary hypertension remains unknown. The present study investigated the RV
      function and TV deformations in patients with isolated TR to find out the
      mechanism and etiology of the disease. METHODS AND RESULTS: Twelve patients with
      isolated, severe TR were included. RV area, volume, ejection fraction (EF),
      tenting distance and tenting area were measured. These parameters were compared
      with 12 age-and gender-matched controls and 12 patients with secondary TR. The
      cause of isolated TR was incomplete coaptation associated with annular dilatation
      without other problems. Compared with the controls, RV end-diastolic volumes and
      annular diameters were significantly larger and RVEF was significantly lower in
      patients with isolated TR. Tenting area and tenting distance were also
      significantly higher. However, there were no significant differences in these
      parameters between patients with isolated and secondary TR. CONCLUSIONS: Isolated
      TR was associated with RV remodeling, systolic dysfunction and resultant annular
      dilatation and tethering of tricuspid leaflets.

PMID- 18728333
TI  - Anatomical investigation of the sinus node artery using dual-source computed
      tomography.
AB  - BACKGROUND: Few investigators have studied the anatomy of the sinus node artery
      (SNA) using noninvasive imaging modalities, so the objective of this study was to
      visualize the in-vivo 3-dimensional anatomical relations of the SNA using dual
      source computed tomography (DSCT). METHODS AND RESULTS: In the 101 patients
      included in this study, the visualization rate, anatomical type and diameter of
      the SNA, the distance between the orifice and coronary artery, and the terminal
      type of SNA were recorded. The visualization rate was 95.2% (96/101). Of 96
      patients, 106 SNAs were detected among which 51 (48.1%, 51/106) originated from
      the right coronary artery, 52 (49.1%, 52/106) from the left circumflex artery,
      and 3 (2.7%, 3/106) from other branches. There were 3 types of SNA: right (n =
      52), left (n = 45), and posterior (n = 9). The distance between the orifice of
      the right SNA and the right coronary sinus was 14.2+/-15.2 mm, for the left SNA
      it was 5.5+/-3.5 mm, and for the posterior SNA, 33.7+/-12.8 mm. The average
      diameter was 1.27+/-0.29 mm. The SNA approached the nodal tissue by 1 of 3
      routes: retrocaval (51.5%), precaval (25.2%), or pericaval (22.3%). CONCLUSION:
      The SNA can be visualized in vivo using DSCT, which is important for preoperative
      knowledge of its origin, course, termination, and anatomical type.

PMID- 18728334
TI  - Clinical role of non-contrast magnetic resonance angiography for evaluation of
      renal artery stenosis.
AB  - BACKGROUND: The association between a gadolinium-based contrast material and
      nephrogenic systemic fibrosis has been discussed. The purpose of our study was to
      evaluate whether non-contrast enhanced magnetic resonance angiography (MRA) might
      provide sufficient information of renal artery stenosis. METHODS AND RESULTS: The
      non-contrast MRA of 26 patients with hypertension was retrospectively reviewed in
      the present study. The significant renal artery stenosis was visually evaluated
      by comparing non-contrast MRA with computed tomography or conventional
      angiographic finding. Difference of the intensities between the proximal and
      distal aorta was quantitatively evaluated. The sensitivity, specificity, positive
      predictive value and negative predictive value of non-contrast MRA in the
      evaluation of the renal artery stenosis was 78%, 91%, 64% and 96%, respectively.
      The distal abdominal aorta showed less signal intensity than the proximal aorta
      by 16.9+/-12.2%. CONCLUSIONS: Non-contrast MRA is a non-invasive and effective
      method that allows evaluation of the renal artery stenosis.

PMID- 18728335
TI  - Prognostic implications of the NT-ProBNP level and left atrial size in non
      ischemic dilated cardiomyopathy.
AB  - BACKGROUND: The ratio of peak early diastolic mitral inflow to annular velocity
      (E/E') and left atrial size could provide prognosis on congestive heart failure
      (CHF). N-terminal Pro B-type natriuretic peptide (NT-ProBNP) has also been useful
      for predicting adverse cardiac events. However, it is not clear how these
      parameters compare with conventional risk factors. Thus, we investigated whether
      E/E', left atrial dimension index (LADI) and NT-ProBNP would predict adverse
      events and add incremental value to conventional risk factors, even in non
      ischemic advanced dilated cardiomyopathy (DCM). METHODS AND RESULTS: Both NT
      ProBNP and echocardiography were evaluated in 105 patients. The cardiac events
      were defined as the composite of cardiac death and re-admission for CHF. At
      follow up, cardiac events occurred in 24 patients who had high NT-ProBNP and
      showed higher LADI and E/E'. In multivariate analysis, both NT-ProBNP and LADI,
      but not E/E', remained as independent predictors; patients with both increased
      LADI and NT-ProBNP had a 27-fold higher risk of cardiac events than those without
      any risk factors (p = 0.003). Moreover, LADI and NT-ProBNP showed a better
      incremental prognostic value over conventional risk factors (global chi-square
      increase from 7 to 17 to 49, p = 0.003, p < 0.001, respectively). CONCLUSIONS:
      Both NT-ProBNP and LADI might have the most predictable power, particularly in
      non-ischemic advanced DCM.

PMID- 18728336
TI  - Comparison of biochemical data, blood pressure and physical activity between
      longevity and non-longevity districts in Japan.
AB  - BACKGROUND: There is controversy about longevity-associated factors, including
      environmental and genetic factors. Clinical and epidemiological studies suggest
      that multiple risk factors decrease life-span, but there has not been a
      definitive report regarding the association of risk factors with longevity. The
      ultimate aim of the present study was to prevent the overwhelming increase in
      life-style-related diseases by evaluating this association in 2 districts in
      Japan. METHODS AND RESULTS: Plasma glucose levels, hemoglobin (Hb) A1c, lipids,
      dehydroepiandrosterone-sulfate, adiponectin and physical activity were examined
      in 133 subjects (M/F 47/86, 67+/-1 years) in Kokufu, a longevity district (mean
      life span: 80.4 years according to 2000 Japanese census) and 69 subjects (M/F
      29/40, 62+/-1 years) in Miyama, a non-longevity district (mean life span 77.4
      years, 2000 census). There were significant differences in systolic and diastolic
      blood pressures (BPs, p < 0.001), exercise capacity (p < 0.0001) and plasma
      adiponectin levels (p < 0.04) between the districts. Plasma adiponectin level was
      significantly correlated with high-density lipoprotein-cholesterol (HDL-C) (r =
      0.333, p < 0.0001), triglyceride (TG) (r = -0.161, p < 0.04), HbA1c (r = -0.163,
      p < 0.03) and HOMA-R (r = -0.163, p < 0.03). CONCLUSION: Life-style-related
      factors such as BP, exercise capacity and plasma adiponectin levels might play an
      important role in longevity, and those of HDL-C and TG, as well as glucose
      tolerance, might be associated with adiponectin levels.

PMID- 18728337
TI  - Japan Arteriosclerosis Longitudinal Study-Existing Cohorts Combine (JALS-ECC):
      rationale, design, and population characteristics.
AB  - BACKGROUND: The Japan Arteriosclerosis Longitudinal Study-Existing Cohorts
      Combine (JALS-ECC) is a pooled study based on individual participant data from
      existing prospective cohort studies in Japan. Its purpose was to consider
      associations between risk factors and cardiovascular disease (CVD) outcomes, as
      well as differences between subgroups, defined by age, gender or geographical
      region, which could not be detected in the smaller samples. METHODS AND RESULTS:
      Individual records for 66,691 participants in 21 cohort studies were pooled,
      accounting for a total of 575,628 person-years. From this data, there were 409
      deaths attributed to stroke and 169 deaths attributed to coronary heart disease
      (CHD). Total stroke and CHD events were 1,478 and 178, respectively. Of the 1,424
      total stroke events with a reported stroke subtype, 975 were classified as
      ischemic, 267 as hemorrhagic, and 178 as subarachnoid hemorrhage. CONCLUSION: The
      JALS-ECC collected data from existing cohort studies covering a diverse Japanese
      population, which has provided information about the effects of modifiable
      factors on the risks of the CVD. Such information should provide a reliable basis
      for establishing prevention strategies.

PMID- 18728338
TI  - Cardiac echinococcosis: recurrent intramyocardial-extracardiac hydatid cysts with
      pericardial protrusion.
AB  - A 26-year-old male patient was diagnosed with an isolated recurrent
      intramyocardial-extracardiac hydatid cyst with pericardial protrusion after being
      admitted with chest pain and palpitation. He had undergone surgical resection of
      an intramyocardial pericardial hydatid cyst without cardiopulmonary bypass 10
      years earlier. In the current admission, the results from transthoracic and
      transesophageal echocardiography and multislice computed tomography were
      confirmed by serological and histopathological tests. The cyst was excised under
      cardiopulmonary bypass, and the patient was treated postoperatively with
      albendazole for 9 months. His clinical status improved postoperatively and he was
      asymptomatic without signs of recurrence as determined by echocardiography.

PMID- 18728339
TI  - Venous hemangioma in the right atrium possibly related to radiofrequency catheter
      ablation.
AB  - Venous hemangioma is a rare, benign cardiac tumor, usually in young or adult
      males. A 61-year-old woman with a clinical history of radiofrequency catheter
      ablation had venous hemangioma of the right atrium diagnosed after an episode of
      acute pain in the precordial region. The incidental discovery of the mass,
      clinical evaluation, operative procedure, pathologic findings and follow-up are
      reported, as well as the epidemiology, natural history, and diagnostic and
      therapeutic approaches. Etiology may be related to damage to endothelial cells of
      the interatrial septum or to endocardial cells.

PMID- 18728340
TI  - Emergency redo mitral valve replacement in a pregnant woman at third trimester:
      case report and literature review.
AB  - Pregnancy carries significant physiological changes that demand more cardiac
      output, so structural cardiac disease can cause life-threatening complications. A
      woman had rheumatic mitral stenosis and underwent mitral valve replacement (MVR)
      with bioprosthesis 8 years prior to admission. She presented with dyspnea and leg
      edema at 30 weeks of gestation. Severe mitral stenosis caused by xenograft
      failure was noted on echocardiography. Management was conservative until a sudden
      onset of hemodynamic compromise requiring emergency redo MVR under normothermic
      cardiopulmonary bypass with intra-aortic balloon pump. Monitoring of fetal
      heartbeat and uterine contractions showed no significant abnormalities and the
      woman gave birth to a full-term baby by Cesarean section with postoperative
      warfarin therapy.

PMID- 18728341
TI  - Multiple myxomas originating from anterior and posterior mitral leaflets in the
      left ventricle leading to LV outflow tract obstruction.
AB  - An extremely rare case of myxomas originating from the mitral leaflets was
      diagnosed in a 64-year-old man presented with a history of exertion dyspnea and
      palpitations. Two masses originating from the anterior and posterior mitral
      leaflets in the left ventricular (LV) cavity, causing LV outflow obstruction,
      were detected by echocardiography. The myxomas were successfully removed with the
      mitral leaflets via left atriotomy and mitral valve replacement. No embolic
      events occurred in the preoperative or postoperative period. In this article, we
      wanted to present.

PMID- 18728343
TI  - Enhancement of radiosensitivity by roscovitine pretreatment in human non-small
      cell lung cancer A549 cells.
AB  - Roscovitine has been reported to have anti-proliferative properties and is in
      process of undergoing clinical trials. In addition to its intrinsic anticancer
      properties, it has recently been suggested that roscovitine may also enhance the
      activity of traditional chemo- and radio- therapies in certain cancer cell lines.
      The purpose of this study was to define the activity of roscovitine in increasing
      radiosensitivity of human non-small cell lung cancer (NSCLC) cell line A549 cells
      in vitro. A549 cells were exposed to ionizing radiation (IR) of gamma-ray with or
      without roscovitine pretreatment. Clonogenic assay was performed and cell cycle
      and apoptosis were analyzed by flow cytometry. Expression of PARP, Ku70 and Ku80
      proteins was detected by Western blot. The active form of caspase-3 positive
      cells were measured by flow cytometry. Our results showed that roscovitine caused
      dose-dependent apoptosis in A549 cells. Pretreatment with minimally toxic
      concentration of roscovitine significantly radiosensitized A549 cells by
      inhibiting colony formation. We then examined potential mechanisms that may
      contribute to the enhanced radiation response induced by roscovitine. Our results
      showed that the combination treatment significantly induced apoptosis in A549
      cells compared to roscovitine or IR treatment alone. Meanwhile, in the co
      treatment group, the percentage of cells with the active form of caspase-3 was
      markedly increased, while roscovitine or IR alone had little effect. Roscovitine
      decreased S phase cells when used alone or in sequential combination with IR.
      Furthermore, this combination treatment blocked DNA repair process after IR,
      indicated by down regulation of Ku70 and Ku80 proteins, while the singly used
      treatment did not. Taken together, these results suggest that roscovitine has the
      potential to act as a radio-sensitizer in A549 cells by promoting caspase-3
      activity and increasing apoptosis, affecting cell cycle distribution and
      impairing DNA repair process.

PMID- 18728344
TI  - Specific residues of RUNX2 are obligatory for formation of BMP2-induced RUNX2
      SMAD complex to promote osteoblast differentiation.
AB  - BMP2 signaling and RUNX2 regulatory pathways converge for transcriptional control
      of bone formation in vivo. SMAD proteins are recruited to RUNX2 regulatory
      complexes via an overlapping nuclear matrix targeting signal/Smad interacting
      domain sequence (391-432) in Runx2. To establish the contribution of RUNX2-SMAD
      interaction to osteoblastogenesis, we characterized a number of point mutants.
      Only a triple mutation of amino acids 426-428 (HTY-AAA) results in loss of RUNX2
      interactions with either BMP2- or TGF-beta- responsive SMADs and fails to
      integrate the BMP2/TGF-beta signal on target gene promoters. In a Runx2 null cell
      reconstitution assay, the HTY mutant did not activate the program of osteoblast
      differentiation (alkaline phosphatase, collagen type 1, osteopontin, bone
      sialoprotein and osteocalcin) in response to BMP2 signaling. Thus, subnuclear
      targeting function and formation of a RUNX2-SMAD osteogenic complex are
      functionally inseparable. Taken together, these studies provide direct evidence
      that RUNX2 is essential for execution and completion of BMP2 signaling for
      osteoblast differentiation.

PMID- 18728345
TI  - Potential role of proprotein convertase SKI-1 in the mineralization of primary
      bone.
AB  - The biochemical mechanism controlling nucleation of mineral crystals in
      developing bone, along with the growth and propagation of these crystals once
      formed, remains poorly understood. To define the nucleation mechanism, a
      proteomics analysis was begun on isolated biomineralization foci (BMF), sites of
      initial crystal nucleation in osteoblastic cell cultures and in primary bone.
      Comparative analyses of the protein profile for mineralized BMF with that for
      total osteoblast cultures revealed the latter were enriched in several proteins
      including BAG-75 and BSP, as well as fragments of each. When 12 protease
      inhibitors were added separately to UMR 106-01 osteoblastic cultures, only the
      serine protease inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride
      (AEBSF) blocked cleavage of BAG-75 and BSP, and prevented mineral crystal
      nucleation within BMF. Consideration of the specificities of the inhibitors
      tested and the fact that AEBSF inhibition was not dependent upon inclusion of FBS
      in the culture media indicated that mineral nucleation does not require serine
      protease plasmin, thrombin, kallikrein, urokinase, C1s or furin. In contrast, SKI
      1 (S1P or site-1) is a membrane-bound serine protease inhibitable by AEBSF. We
      show here for the first time that mineralizing UMR 106 cells express a 98-kDa
      active, soluble form of SKI-1 within BMF. In contrast, nonmineralizing UMR cells
      appear to differentially process SKI-1 into smaller immunoreactive fragments (<35
      kDa). These findings suggest that SKI-1 plays a direct or indirect role in
      assembly of functional nucleation complexes containing BAG-75 and BSP and their
      fragments, thus facilitating initial mineral nucleation within these
      biomineralization foci.

PMID- 18728346
TI  - Phosphorylation of osteopontin peptides mediates adsorption to and incorporation
      into calcium oxalate crystals.
AB  - Phosphorylated peptides of osteopontin (OPN) have been shown to inhibit the
      growth of the {100} face of calcium oxalate monohydrate (COM). The inhibitory
      potency has been shown to be dependent on the phosphate content of the peptide.
      The purpose of this study is to better understand the means by which phosphate
      groups promote crystal growth inhibition by OPN peptides. Peptides of rat bone
      OPN 220-235 peptides have been synthesized with zero (P0), 1 (P1) or 3 (P3)
      phosphate modifications. COM crystals were grown in the presence of 0.1-10 microg
      of P0, P1 or P3. P0 incorporation into COM crystals was evident at 10 microg/ml
      of peptide, whereas the phosphorylated peptides P1 and P3 were incorporated at
      all tested concentrations. At 5 microg/ml of P3, COM crystals exhibited a
      'dumbbell' morphology. To study the peptide-mineral interaction, surface
      frequency plots were constructed from molecular dynamics simulations of OPN
      peptide adsorption. Carboxylate and phosphate groups were found to adsorb in
      specific orientations to the COM {100} surface. In conclusion, it appears that
      the phosphate groups on OPN peptides are capable of interacting with the COM
      {100} surface. This interaction appears to increase the adsorption energy of the
      peptide to the surface, thus enhancing its inhibitory potency.

PMID- 18728347
TI  - Progressive ankylosis gene (ank) regulates osteoblast differentiation.
AB  - The progressive ankylosis gene (ank) is a transmembrane protein that transports
      intracellular pyrophosphate to the extracellular milieu. Human mutations of ank
      lead to craniometaphyseal dysplasia, a disease which is characterized by the
      overgrowth of craniofacial bones and osteopenia in long bones, suggesting that
      ANK plays a regulatory role in osteoblast differentiation. To determine the role
      of ANK in osteoblast differentiation, we suppressed ANK expression in the
      osteoblastic MC3T3-E1 cell line using siRNA and determined the expression of
      osteoblastic marker genes and the transcription factors osterix and runx2. In
      addition, we determined the osteoblastic differentiation of bone marrow stromal
      cells isolated from the bone marrow of ank/ank mice, which express a truncated,
      nonfunctional ANK protein, or wild-type littermates. Suppression of ANK
      expression in MC3T3-E1 cells led to a decrease in bone marker gene expression,
      including alkaline phosphatase, bone sialoprotein, osteocalcin and type I
      collagen. In addition, osterix gene expression was decreased in ANK expression
      suppressed MC3T3 cells, whereas runx2 expression was increased. Bone marrow
      stromal cells isolated from ank/ank mice cultured in the presence of ascorbate-2
      phosphate for up to 35 days showed markedly reduced mineralization compared to
      the mineralization of bone marrow stromal cells isolated from wild-type
      littermates. In conclusion, these findings suggest that ANK is a positive
      regulator of differentiation events towards a mature osteoblastic phenotype.

PMID- 18728348
TI  - The composition of bovine peritubular dentin: matching TOF-SIMS, scanning
      electron microscopy and biochemical component distributions. New light on
      peritubular dentin function.
AB  - Peritubular dentin (PTD) is a hypermineralized phase within the dentinal tubules
      in some vertebrate teeth as an interface between the intertubular dentin (ITD)
      and the cell processes. Our aim has been to understand the composition, structure
      and role of PTD as a mineralized tissue. We have utilized the technique of time
      of flight secondary ion mass spectrometry (TOF-SIMS) to map the distribution of
      positive and negative inorganic ions as well as organic components in the fully
      mineralized, intact PTD structure in bovine tooth cross-sections, and correlated
      these with scanning electron microscopy (SEM) in standard and backscatter modes.
      In recent work, we developed a procedure to freeze fracture the teeth and
      separate PTD from the less dense ITD by the use of aqueous sodium
      phosphotungstate step density gradients, after degrading the ITD collagen with
      NaOCl. Here, PTD-containing fragments were characterized by SEM and TOF-SIMS
      surface structure analysis. The TOF-SIMS data show that the isolated PTD does not
      contain collagen, but its surface is rich in glutamic acid-containing protein(s).
      The TOF-SIMS spectra also indicated that the intact PTD fragments contain
      phospholipids, and chemical analyses showed phosphatidylserine,
      phosphatidylinositol and phosphatidylcholine as the principal lipid components.
      In SEM sections, untreated PTD shows as a smooth collar around the tubule, but
      after digestion with ethylenediamine to remove all organic components, the porous
      nature of the mineral phase of small, thin platy apatite crystals becomes
      evident. Thus, the organic matrix of PTD appears to be a proteolipid-phospholipid
      complex.

PMID- 18728349
TI  - Studies of the DMP1 57-kDa functional domain both in vivo and in vitro.
AB  - Dmp1-null mice and patients with mutations in dentin matrix protein 1 (DMP1)
      resulting in autosomal recessive hypophosphatemic rickets display similar
      skeletal defects. As mutations were observed in the last 18 amino acids of DMP1
      in 1 subset of patients and as fragments of intact DMP1, a 37-kDa N-terminal and
      a 57-kDa C-terminal fragment, have been purified from bone and dentin, we
      hypothesized that the cleaved 57-kDa C-terminal fragment is the essential
      functional domain of DMP1. To test this hypothesis, different forms of
      recombinant DMP1 were expressed in 293EBNA, CHO and 2T3 cells. The results showed
      that DMP1 was processed into a 37-kDa N-terminal and a 57-kDa C-terminal fragment
      in vitro in all cell lines examined. DMP1 processing in CHO cells was blocked by
      a furin protease inhibitor, decanoyl-Arg-Val-Lys-Arg-chloromethyl ketone, in a
      dose-dependent manner. Coexpression of PHEX, a potential upstream protease, had
      no apparent effect on DMP1 cleavage in 293EBNA cells, suggesting that PHEX may
      not be required for DMP1 processing. To test the in vivo role of the C-terminal
      fragment, transgenic mice overexpressing full-length DMP1 or the 57-kDa fragment
      controlled by the 3.6-kb Col1 promoter were generated. Overexpression of these
      transgenes had no effect on the wild-type skeleton, but on the Dmp1-null
      background showed expression in the osteoblast layer and throughout the bone
      matrix leading to the rescue of the null bone phenotype. This suggests that the
      57-kDa C-terminal fragment may be able to recapitulate the function of intact
      DMP1 in vivo.

PMID- 18728350
TI  - Activation of the mitogen-activated protein kinase pathway by bone sialoprotein
      regulates osteoblast differentiation.
AB  - Bone sialoprotein (BSP) is an abundant protein in the extracellular matrix of
      bone that has been suggested to have several different physiological functions,
      including the nucleation of hydroxyapatite (HA), promotion of cell attachment and
      binding of collagen. Studies in our lab have demonstrated that increased
      expression of BSP in osteoblast cells can increase expression of the osteoblast
      related genes Runx2 and Osx as well as alkaline phosphatase and osteocalcin and
      increase matrix mineralization. To determine the molecular mechanisms responsible
      for the BSP-mediated increase in osteoblastic differentiation, several functional
      domain mutants of BSP were expressed in primary rat bone osteoblastic cells,
      including the contiguous glutamic acid sequences (polyGlu) and the arginine
      glycine-aspartic acid (RGD) motif. Markers of osteoblast differentiation,
      including matrix mineralization and alkaline phosphatase staining, were increased
      in cells expressing BSP mutants of the polyGlu sequences but not in cells
      expressing RGD-mutated BSP. We also determined the dependence on integrin
      associated pathways in promoting BSP-mediated differentiation responses in
      osteoblasts by demonstrating the activation of focal adhesion kinase, MAP kinase
      associated proteins ERK1/2, ribosomal s6 kinase 2 and the AP-1 protein cFos.
      Thus, the mechanism regulating osteoblast differentiation by BSP was determined
      to be dependent on integrin-mediated intracellular signaling pathways.

PMID- 18728351
TI  - Tiotropium bromide attenuates respiratory syncytial virus replication in
      epithelial cells.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) infection could be related to
      airway inflammation as well as exacerbation of chronic obstructive pulmonary
      disease (COPD). Tiotropium bromide decreases the frequency of exacerbation in
      patients with COPD; however, the mechanisms of tiotropium bromide to reduce the
      chances of exacerbation have not been defined. One potential mechanism could be
      that tiotropium bromide protects against RSV infection in epithelial cells.
      OBJECTIVE: To examine whether tiotropium bromide affects RSV replication in HEp-2
      cells. METHODS: The supernatant titer of RSV was calculated by methylcellulose
      plaque assay after RSV innoculation. Intracellular RSV and ICAM-1 mRNA were
      measured by PCR. Syncytium formation was observed by light microscopy.
      Intracellular RSV fusion protein and RhoA protein were detected by Western blot
      analysis. Furthermore, RhoA activity, ICAM-1 expression and inflammatory
      cytokines in cultured supernatant were measured by binding assay,
      immunofluorescence staining and ELISA, respectively. RESULTS: Tiotropium bromide
      decreased the supernatant titer of RSV, and it inhibited syncytium formation,
      RhoA activation and ICAM-1 expression. Moreover, it suppressed the production of
      IL-6 and IL-8 after RSV infection. CONCLUSIONS: The antiviral effects of
      tiotropium bromide regarding RSV replication are partly due to inhibition of RhoA
      activity and ICAM-1 expression. Tiotropium bromide decreases RSV replication and
      may modulate airway inflammation by reducing the production of inflammatory
      cytokines.

PMID- 18728352
TI  - Enamel tissue engineering using subcultured enamel organ epithelial cells in
      combination with dental pulp cells.
AB  - We describe a strategy for the in vitro engineering of enamel tissue using a
      novel technique for culturing enamel organ epithelial (EOE) cells isolated from
      the enamel organ using 3T3-J2 cells as a feeder layer. These subcultured EOE
      cells retain the capacity to produce enamel structures over a period of extended
      culture. In brief, enamel organs from 6-month-old porcine third molars were
      dissociated into single cells and subcultured on 3T3-J2 feeder cell layers. These
      subcultured EOE cells were then seeded onto a collagen sponge in combination with
      primary dental pulp cells isolated at an early stage of crown formation, and
      these constructs were transplanted into athymic rats. After 4 weeks, complex
      enamel-dentin structures were detected in the implants. These results show that
      our culture technique maintained ameloblast lineage cells that were able to
      produce enamel in vivo. This novel subculture technique provides an important
      tool for tooth tissue engineering.

PMID- 18728353
TI  - Activation of Sirt1 decreases adipocyte formation during osteoblast
      differentiation of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSC) can differentiate into osteoblasts, adipocytes,
      chondrocytes and myoblasts. It has been suggested that a reciprocal relationship
      exists between the differentiation of MSC into osteoblasts and adipocytes.
      Peroxisome proliferator-activated receptor gamma2 (PPARgamma2) is a key element
      for the differentiation into adipocytes. Activation of the nuclear protein
      deacetylase Sirt1 has recently been shown to decrease adipocyte development from
      preadipocytes via inhibition of PPARgamma2. In vitro, MSC differentiate to
      osteoblasts when exposed to bone-inducing medium. However, adipocytes are also
      developed. In the present study we have targeted Sirt1 to control adipocyte
      development during differentiation of MSC into osteoblasts. The finding that
      resveratrol and isonicotinamide markedly inhibited adipocyte and promoted
      osteoblast differentiation demonstrates an interesting alternative to PPARgamma
      antagonists. These results are important for the evolving field of cell-based
      tissue engineering, but may also be relevant in the search for new treatments of
      osteoporosis.

PMID- 18728354
TI  - Time lapse imaging techniques for comparison of mineralization dynamics in
      primary murine osteoblasts and the late osteoblast/early osteocyte-like cell line
      MLO-A5.
AB  - Mineralization of bone matrix and osteocyte differentiation occur simultaneously
      and appear interrelated both spatially and temporally. Although these are dynamic
      events, their study has been limited to using static imaging approaches, either
      alone or in combination with chemical and biochemical analysis and/or genetic
      manipulation. Here we describe the application of live cell imaging techniques to
      study mineralization dynamics in primary osteoblast cultures compared to a late
      osteoblast/early osteocyte-like cell line, MLO-A5. Mineral deposition was
      monitored using alizarin red as a vital stain for calcium. To monitor
      differentiation into an osteocyte-like phenotype, the calvarial cells were
      isolated from transgenic mice expressing green fluorescent protein (GFP) driven
      by an 8-kb dentin matrix protein-1 (Dmp1) promoter that gives osteocyte-selective
      expression. Time lapse imaging showed that there was a lag phase of 15-20 h after
      beta-glycerophosphate addition, followed by mineral deposition that was rapid in
      primary osteoblast cultures but more gradual in MLO-A5 cultures. In primary
      osteoblast cultures, mineral was deposited exclusively in association with
      clusters of cells expressing Dmp1-GFP, suggesting that they were already
      differentiating into osteocyte-like cells. In MLO-A5 cells, the first indication
      of mineralization was the appearance of punctate areas of alizarin red
      fluorescence of 4-7 mum in diameter, followed by mineral deposition throughout
      the culture in association with collagen fibrils. A high amount of cell motility
      was observed within mineralizing nodules and in mineralizing MLO-A5 cultures.
      These studies provide a novel approach for analyzing mineralization kinetics that
      will enable us to dissect in a time-specific manner the essential players in the
      mineralization process.

PMID- 18728355
TI  - The derivation of mesenchymal stem cells from human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) hold promise for tissue regeneration therapies
      by providing a potentially unlimited source of cells capable of undergoing
      differentiation into specified cell types. Several preclinical studies and a few
      clinical studies use human bone marrow stromal cells (hBMSCs) to treat skeletal
      diseases and repair damaged tissue. However, hBMSCs have limited proliferation
      and differentiation capacity, suggesting that an alternate cell source is
      desirable, and hESCs may serve this purpose. Here we describe a protocol for the
      reproducible derivation of mesenchymal stem cells from hESCs (hES-MSCs). The hES
      MSCs have a similar immunophenotype to hBMSCs, specifically they are CD73+, STRO
      1+ and CD45-, and are karyotypically stable. The derived hES-MSCs are also
      capable of differentiating into osteoblasts and adipocytes. When the hES-MSCs
      were genetically modified with the lineage-specific Col2.3-GFP lentivirus and
      cultured in osteogenic medium, increased GFP expression was detected over time,
      indicating the hES-MSCs have the capacity to differentiate down the osteogenic
      lineage and had progressed toward a mature osteoblast phenotype.

PMID- 18728356
TI  - Transcriptional regulation of osteoblasts.
AB  - The differentiation of osteoblasts from mesenchymal precursors requires a series
      of cell fate decisions controlled by a hierarchy of transcription factors. These
      include RUNX2, Osterix (OSX), ATF4 and a large number of nuclear coregulators.
      During bone development, initial RUNX2 expression coincides with the formation of
      mesenchymal condensations and precedes the branching of chondrogenic and
      osteogenic lineages. Given its central role in bone development, it is not
      surprising that RUNX2 is subject to a variety of controls. These include
      posttranslational modification, especially phosphorylation, and interactions with
      accessory nuclear factors. Specific examples of RUNX2 regulation to be reviewed
      include phosphorylation by the ERK/MAP kinase pathway and interactions with DLX5.
      RUNX2 is regulated via phosphorylation of critical serine residues in the
      proline/serine/threonine domain. In vivo, the transgenic expression of
      constitutively active MAP kinase in osteoblasts accelerated skeletal development,
      while a dominant-negative MAPK retarded development in a RUNX2-dependent manner.
      DLX5-RUNX2 complexes can be detected in osteoblasts and this interaction plays a
      critical role in maintaining osteoblast-specific expression of the bone
      sialoprotein gene. These studies allow us to begin understanding the complex
      mechanisms necessary to fine-tune bone formation as mesenchymal progenitors
      progress down the osteoblast lineage.

PMID- 18728357
TI  - Msx1 expression regulation by its own antisense RNA: consequence on tooth
      development and bone regeneration.
AB  - Msx homeogenes play an important role in epithelial-mesenchymal interactions
      leading development. Msx1 is relevant for dental and craniofacial morphogenesis,
      as suggested by phenotypes of Msx1 mutations in human and Msx1 KO mice. During
      adulthood, Msx1 is still expressed in the skeleton where its role is largely
      unknown. Our group showed that the Msx1 gene is submitted to bidirectional
      transcription generating a long noncoding antisense (AS) RNA. During tooth
      development, Msx1 sense (S) and AS RNAs showed specific patterns of expression.
      Thus, the aim of the present study was to analyze the relation between Msx1 S and
      AS RNAs. In vivo mapping in adult mice showed that both Msx1 RNAs were detected
      in tested tissues such as bone. In vitro, Msx1 AS RNA decreased endogenous Msx1 S
      expression and modified Msx1 protein cell distribution. Regulations of Dlx5 and
      Bmp4 expression involving Msx1 S and AS RNAs showed that Msx1 AS RNA could
      modulate Msx1 function. The study of Msx1 S and AS RNA status is interesting in
      the case of tooth agenesis and bone loss to see if a disturbance of this balance
      could be associated with a disturbance of bone homeostasis. In that sense, our
      current results suggest a clear involvement of Msx1 in alveolar bone.

PMID- 18728358
TI  - Thromboembolic complications in splenectomized patients with dominantly inherited
      beta-thalassemia.

PMID- 18728359
TI  - Long-term prognosis of steroid-dependent sensorineural hearing loss.
AB  - We report on the long-term follow-up of 15 patients with steroid-dependent
      sensorineural hearing loss (SDSNHL), which was steroid dose dependent. We
      classified the patients into 2 groups: group A consisted of 6 patients with
      systemic SDSNHL, and group B consisted of 9 patients with inner-ear-specific
      SDSNHL without systemic disease. Group B patients were further classified as
      patients with slowly or rapidly progressive hearing loss. The yearly rate of
      hearing deterioration was greater in group B than in group A. Thus, the long-term
      hearing prognosis of patients in group B was worse than those in group A.
      Although SDSNHL may have immune-related origins, we hypothesize that hearing
      deterioration may be caused by proinflammatory cytokines because many of our
      cases exhibited abnormal immunological laboratory values and because many of
      these cases responded favorably to steroid treatment.

PMID- 18728360
TI  - Chronic bronchitis and acute infections as new risk factors for ischemic stroke
      and the lack of protection offered by the influenza vaccination.
AB  - BACKGROUND AND PURPOSE: Acute and chronic infections may play a role in promoting
      complications of atherosclerotic disease. We evaluated the importance of acute
      infections and chronic bronchitis (CB; as a chronic inflammatory state) in
      several subtypes of ischemic stroke, and we investigated whether the influenza
      vaccination was independently associated with a reduced likelihood of stroke.
      METHODS: A case-control study was performed on 393 consecutive ischemic stroke
      patients and 393 control subjects matched for age, sex and time of year. Data
      were collected by a structured interview that assessed risk factors, acute
      infections within the preceding 2 months, CB and whether they had received the
      influenza vaccination. RESULTS: Infections within the 2 months before stroke
      onset and CB were more common among patients than control subjects [23.3 vs.
      16.3% (p = 0.014) and 17.2 vs. 8.5% (p = 0.001), respectively]. After adjustment
      for traditional risk factors, the risk of stroke was increased in the subjects
      with CB (OR = 1.83, 95% CI = 1.35-2.48, p = 0.016), but not with acute infection
      (OR = 1.32, 95% CI = 0.98-1.78, p = 0.16). Acute infections and CB increased the
      risk of ischemic events in all age groups; this reached significance for patients
      older than 60 years. The profile of vascular risk factors was similar in patients
      with and without previous infections. The influenza vaccination did not prevent
      ischemic stroke, and it did not reduce the rate of acute previous infections in
      stroke patients. CONCLUSIONS: CB and infections over the previous 2 months
      predicted the risk of ischemic stroke. The influenza vaccination was not
      associated with a reduction in the incidence of stroke in our group of patients.

PMID- 18728361
TI  - Weather as a trigger of stroke. Daily meteorological factors and incidence of
      stroke subtypes.
AB  - BACKGROUND: The conclusions of previous studies show little agreement concerning
      the relationship between weather and the incidence of stroke. We analyse the
      relationship between daily meteorological conditions and daily as well as
      seasonal stroke incidence. METHODS: 1,286 consecutive strokes assessed during 3
      years (2001-2003) from the reference area of Hospital del Mar were classified as
      intracerebral haemorrhage (ICH) (n = 243) or ischaemic stroke (IS) (n = 1,043).
      IS was divided in non-lacunar stroke (NLS) (n = 732) and lacunar stroke (LS) (n =
      311). Daily meteorological data were obtained from 'Observatori Fabra' of
      Barcelona: atmospheric pressure (AP), relative humidity, maximum, minimum, and
      mean temperatures, and the variation of all these measures compared with the
      previous day. RESULTS: Total stroke (TS) incidence showed little association with
      AP (coefficient of confidence, CC: -0.072; p = 0.022), but was higher with the AP
      variations (CC: 0.127; p < 0.001). NLS were related to AP falls (OR: 2.41; p <
      0.001) whilst ICHs were associated with AP rises (OR: 2.07; p = 0.01). NLS and
      temperature showed an inverse correlation; however, it lost its significance
      after adjusting for AP variations. The daily incidences of NLS and ICH were
      higher in autumn and in winter, but depended strongly on the daily variations of
      AP. No other associations were found. CONCLUSIONS: The incidences of NLS and ICH
      are related to AP changes compared with the previous day. AP changes largely
      explain the seasonal and daily variations in the incidence of stroke. These data
      may help to explain the controversy in previous studies and to promote studies
      focused on the trigger mechanisms of stroke.

PMID- 18728362
TI  - Early neurological deterioration following intravenous recombinant tissue
      plasminogen activator therapy in patients with acute lacunar stroke.
AB  - BACKGROUND: The aim of this study was to examine the rate of early neurological
      deterioration (END) and favorable outcomes after acute lacunar stroke following
      the use of intravenous recombinant tissue plasminogen activator (IV rtPA).
      METHODS: A total of 76 acute lacunar stroke patients (<12 h from symptom onset)
      were enrolled during a 1-year period (n = 76). Comparisons were made between
      those who received (group A; n = 29) or did not receive (group B; n = 47) IV
      rtPA. RESULTS: END/favorable outcomes were observed in 24/31% of the subjects in
      group A and 21/23% in group B (p = 0.77/0.46). Subgroup analysis of the etiologic
      subtype of small-vessel occlusion showed that END/favorable outcomes were
      observed in about 33/33% and 15/19% of the patients in groups A and B,
      respectively (p = 0.21/0.34). CONCLUSIONS: The authors showed that the use of
      rtPA in cases of no lysible clots might not affect the END and favorable
      outcomes.

PMID- 18728363
TI  - The JNK inhibitor XG-102 protects from ischemic damage with delayed intravenous
      administration also in the presence of recombinant tissue plasminogen activator.
AB  - BACKGROUND: XG-102 (formerly D-JNKI1), a TAT-coupled dextrogyre peptide which
      selectively inhibits the c-Jun N-terminal kinase, is a powerful neuroprotectant
      in mouse models of middle cerebral artery occlusion (MCAo) with delayed
      intracerebroventricular injection. We aimed to determine whether this
      neuroprotection could also be achieved by intravenous injection of XG-102, which
      is a more feasible approach for future use in stroke patients. We also tested the
      compatibility of the compound with recombinant tissue plasminogen activator
      (rtPA), commonly used for intravenous thrombolysis and known to enhance
      excitotoxicity. METHODS: Male ICR-CD1 mice were subjected to a 30-min-suture
      MCAo. XG-102 was injected intravenously in a single dose, 6 h after ischemia.
      Hippocampal slice cultures were subjected to oxygen (5%) and glucose (1 mM)
      deprivation for 30 min. rtPA was added after ischemia and before XG-102
      administration, both in vitro and in vivo. RESULTS: The lowest intravenous dose
      achieving neuroprotection was 0.0003 mg/kg, which reduced the infarct volume
      after 48 h from 62 +/- 19 mm(3) (n = 18) for the vehicle-treated group to 18 +/-
      9 mm(3) (n = 5, p < 0.01). The behavioral outcome was also significantly improved
      at two doses. Addition of rtPA after ischemia enhanced the ischemic damage both
      in vitro and in vivo, but XG-102 was still able to induce a significant
      neuroprotection. CONCLUSIONS: A single intravenous administration of XG-102
      several hours after ischemia induces a powerful neuroprotection. XG-102 protects
      from ischemic damage in the presence of rtPA. The feasibility of systemic
      administration of this promising compound and its compatibility with rtPA are
      important steps for its development as a drug candidate in ischemic stroke.

PMID- 18728364
TI  - Ischemic findings of T2*-weighted 3-tesla MRI in acute stroke patients.
AB  - BACKGROUND: We compared ischemic findings on gradient echo-type T(2)*-weighted
      images at 3-tesla MRI (T(2)*WI) in patients with acute ischemia and major vessel
      occlusion, and stroke patients with lacunar infarction or branch atheromatous
      disease. METHODS: Our study population consisted of 45 patients with acute
      stroke. They underwent 3-tesla MRI within 12 h of stroke onset. Included were 24
      patients (13 men and 11 women, mean age 68 years) with major vessel occlusion and
      21 patients (11 men and 10 women, mean age 69 years) with minor infarction such
      as lacunar infarcts or branch atheromatous disease. We classified vascular
      ischemic findings of T(2)*WI into 3 sign categories, i.e. artery susceptibility
      sign, cortical vessel sign (hypointensity and enlargement of the cortical
      vessels) and brush sign (hypointensity of vessels in the deep white matter).
      Decreased intensity in the ischemic parenchyma was designated ischemic tissue
      sign. We compared regions of interest in the hypoperfused area on flow-sensitive
      alternating inversion recovery (FAIR) images with our vascular ischemic findings.
      RESULTS: None of the vascular ischemic signs nor the ischemic tissue sign were
      found in patients with minor vessel disease. All 24 patients with major vessel
      occlusion manifested the cortical vessel sign, 23 the brush sign. The area with
      ischemic vessel signs on T(2)*WI was almost as large or somewhat smaller than the
      hypoperfused area on FAIR images. Compared to the contralateral side, 14 of 24
      patients (58.3%) with major vessel occlusion showed decreased intensity in the
      ischemic parenchyma (ischemic tissue sign). Region of interest measurements on
      FAIR images demonstrated greater hypoperfusion in the area classified as ischemic
      tissue sign on T(2)*WI. CONCLUSIONS: Ischemic vessel signs and the ischemic
      tissue sign on T(2)*WI at 3 T would be useful to evaluate the extensive ischemia
      due to major vessel occlusion and may be correlated with the blood-oxygen-level
      dependent effect due to increased deoxyhemoglobin. The ischemic tissue sign may
      be reflective of severe ischemia.

PMID- 18728365
TI  - Age accounts for racial differences in ischemic stroke volume in a population
      based study.
AB  - BACKGROUND: The stroke volume among black ischemic stroke patients in phase I of
      the population-based Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS)
      was smaller than reported among acute stroke studies, with a median stroke volume
      of 2.5 cm. However, it is not known if stroke volume was similar between black
      and white patients within the same study population. METHODS: Phase II of the
      GCNKSS identified all ischemic strokes between July 1993 and June 1994. The
      stroke volume was estimated by study physicians using the modified ellipsoid
      method. Analysis of stroke volume by race, sex and age was performed for strokes
      with a measurable lesion of >or=0.5 cm(3). RESULTS: Among verified cases of
      ischemic stroke, 334 patients were eligible for this analysis. There were 191
      whites (57%) and 143 blacks (43%). The mean age was 69.4 years. The median stroke
      volume for all patients was 8.8 cm(3) (range 0.5-540), with a mean of 36.4 cm(3).
      Stroke volume was not different between men and women, and it tended to increase
      with age. Although stroke volume was significantly higher among whites, age was a
      confounding factor. Subsequent analysis of stroke volume stratified by age showed
      no difference between blacks and whites in any age group. CONCLUSIONS: Our data
      show that most ischemic stroke lesions, regardless of the race, are of small
      size, and this may be an important reason for the low percentage of strokes
      treated currently with tissue-type plasminogen activator. The association of age
      with stroke volume requires further study.

PMID- 18728366
TI  - Capecitabine and cisplatin combination is an active and well-tolerated doublet in
      the treatment of metastatic breast carcinoma patients pretreated with
      anthracycline and taxanes.
AB  - Our aim was to evaluate the activity and toxicity of capecitabine and cisplatin
      (CapCisp) combination in anthracycline- and taxane-pretreated metastatic breast
      cancer patients. Thirty-three patients, 20-61 years of age (median 41), were
      included. They received Cap 2,000 mg/m(2) on days 1-14 and Cisp 60 mg/m(2) on day
      1, repeated every 3 weeks. Twelve nonprogressive patients continued single-agent
      Cap therapy until progression or until intolerable toxicity after Cisp cessation.
      The disease control rate in 154 cycles was 81.8%: complete response 3.0% (n = 1),
      partial response 48.5% (n = 16) and stable disease 30.3% (n = 10). The median
      time to disease progression was 6.3 months (95% CI 3.8-8.8). The median overall
      survival was 11.5 months (95% CI 6.9-16.1). The only grade 3 toxicity was
      neutropenia, observed in 4 patients (12.1%). CapCisp has an encouraging anti
      tumor activity with a low toxicity rate in anthracycline- and taxane-pretreated
      metastatic breast cancer patients.

PMID- 18728368
TI  - Uptake and release of fluoride from fluoride-impregnated chewing sticks (miswaks)
      in vitro and in vivo.
AB  - The purpose was to investigate the uptake and release of fluoride (F) from F
      impregnated chewing sticks (miswaks). In the first series, 3-cm-long pieces were
      impregnated in 1, 2, 3 and 4% NaF solutions for 3 h, 1 day and 3 days (10
      pieces/test). There was a dose-response effect with respect to both impregnation
      time and the concentration of the F solution. In the second and third series,
      totally 40 miswak pieces were impregnated in 3% NaF for 1 day and 3 days; the
      outer layer (bark) was separated from the inner spongy part (pulp) and analyzed
      separately. F was released from both parts, but somewhat more was released from
      the bark than from the pulp; a plateau was reached at around 30 min. In vivo, 9
      healthy subjects used three products for 2 min in a crossover design: (1) a
      miswak impregnated in 3% NaF for 1 day, (2) a miswak impregnated in 3% NaF for 3
      days, and (3) 1 g of F toothpaste (containing 1,450 ppm F as NaF) on a
      toothbrush. The highest F concentration at the approximal area was obtained after
      using the miswak impregnated in 3% NaF for 3 days compared with the other
      products (p < 0.05 or p < 0.01). To conclude, NaF-impregnated miswaks produced a
      rapid release of F in vitro as well as in vivo and may be an interesting vehicle
      for home care use for caries prevention in countries where they are used
      regularly.

PMID- 18728367
TI  - Dental caries increments and related factors in children with type 1 diabetes
      mellitus.
AB  - The aim of this study was to analyse possible associations between caries
      increments and selected caries determinants in children with type 1 diabetes
      mellitus and their age- and sex-matched non-diabetic controls, over 2 years. A
      total of 63 (10-15 years old) diabetic and non-diabetic pairs were examined for
      dental caries, oral hygiene and salivary factors. Salivary flow rates, buffer
      effect, concentrations of mutans streptococci, lactobacilli, yeasts, total IgA
      and IgG, protein, albumin, amylase and glucose were analysed. Means of 2-year
      decayed/missing/filled surface (DMFS) increments were similar in diabetics and
      their controls. Over the study period, both unstimulated and stimulated salivary
      flow rates remained significantly lower in diabetic children compared to
      controls. No differences were observed in the counts of lactobacilli, mutans
      streptococci or yeast growth during follow-up, whereas salivary IgA, protein and
      glucose concentrations were higher in diabetics than in controls throughout the 2
      year period. Multivariable linear regression analysis showed that children with
      higher 2-year DMFS increments were older at baseline and had higher salivary
      glucose concentrations than children with lower 2-year DMFS increments. Likewise,
      higher 2-year DMFS increments in diabetics versus controls were associated with
      greater increments in salivary glucose concentrations in diabetics. Higher
      increments in active caries lesions in diabetics versus controls were associated
      with greater increments of dental plaque and greater increments of salivary
      albumin. Our results suggest that, in addition to dental plaque as a common
      caries risk factor, diabetes-induced changes in salivary glucose and albumin
      concentrations are indicative of caries development among diabetics.

PMID- 18728369
TI  - [Voice-related quality of life: structure, validity and factors of the German
      questionnaire].
AB  - In this study, structure and validity of the German version of the Voice-Related
      Quality of Life (V-RQOL) questionnaire and its correlation to age, gender, and
      type of dysphonia (organic vs. functional) were assessed. Correlations of the V
      RQOL result on the one hand and emotional and physical complaints on the other
      hand were investigated. Data were collected in 62 adult patients with dysphonia
      of benign origin and the following results were found: the German version of the
      V-RQOL questionnaire describes voice-related quality of life in one single value.
      Age, gender and type of dysphonia do not influence its result. Dysphonic patients
      present with an increased number of emotional and physical complaints when
      compared with normative values derived from the literature. However, not all of
      these complaints correlate with voice-related quality of life at a significant
      level.

PMID- 18728370
TI  - A new formula for predicting liver metastasis in patients with colorectal cancer:
      immunohistochemical analysis of a large series of 439 surgically resected cases.
AB  - OBJECTIVE: The purpose of this study was to establish a new formula predicting
      liver metastasis in patients with colorectal cancer (CRC). METHODS: Nine
      previously reported predictive markers for liver metastasis and/or prognosis (COX
      2, dysadherin, E-cadherin, beta-catenin, Ki-67, p53, laminin5gamma2, matrilysin
      and MUC-1) were immunohistochemically investigated in 439 consecutive patients
      with CRC. We tried to determine the combination of molecules which best predicted
      liver metastasis. A formula for predicting liver metastasis was constructed using
      a training cohort comprising 150 cases, and applied to a validation cohort
      comprising 190 cases and another comprising 99 cases from an outside hospital.
      RESULTS: A combination of dysadherin, E-cadherin and matrilysin was identified to
      be best for predicting liver metastasis (area under the curve value, 0.807). The
      predictive formula: 3x dysadherin score [0 for low expression (</=50% of tumor
      cells positive) or 1 for high expression (>50%)] + 4x E-cadherin score [0 for
      preserved (>80% of tumor cells positive) or 1 for reduced (</=80%)] + 2x
      matrilysin score [0 for low expression (</=30% of tumor cells positive) or 1 for
      high expression (>30%)] was able to discriminate patients with liver metastasis
      in the training cohort with a sensitivity of 85.7% and a specificity of 58.9%.
      The discriminative capacity of the formula was validated in the first cohort with
      a sensitivity of 87.0% and a specificity of 66.5%, and in the second cohort with
      a sensitivity of 80% and a specificity of 60.0%. CONCLUSIONS: We have established
      a formula for predicting liver metastasis in patients with CRC, and confirmed
      that it has a high sensitivity potentially useful for clinical application.

PMID- 18728371
TI  - Paclitaxel- and platinum-based postoperative chemotherapy for primary fallopian
      tube carcinoma: a single institution experience.
AB  - BACKGROUND: Primary fallopian tube carcinoma (PFTC) is a rare gynecologic
      malignancy with very few data existing on the activity of the combination of
      paclitaxel with a platinum analogue as adjuvant chemotherapy. METHODS: We
      retrospectively analyzed 41 consecutive patients with PFTC who were treated
      postoperatively with paclitaxel- and platinum-containing chemotherapy regimens.
      RESULTS: We observed 12 (63.2%) complete and 6 (31.6%) partial responses among 19
      patients with measurable disease. The median time to disease progression (TTP)
      for all patients was 68 months. The median overall survival (OS) for all patients
      has not been reached yet. The median TTP was 84 months for patients with stage
      I/II disease and 34 months for patients with advanced disease (p = 0.017). Median
      OS has not been reached yet for patients with stage I/II PFTC, while it was 63.8
      months for patients with stage III/IV disease (p = 0.002). Furthermore, OS has
      not been reached yet for patients with optimally debulked tumors, while it was
      34.1 months for patients with residual disease >2 cm (p < 0.0001). CONCLUSION:
      Adjuvant platinum- and paclitaxel-based chemotherapy should be regarded as the
      standard treatment in patients with PFTC. Early stage disease and optimal
      debulking are associated with improved TTP and OS.

PMID- 18728372
TI  - [Incidence of aspirin resistance in the patient group of a university hospital in
      Korea].
AB  - BACKGROUND: Aspirin is the most common drug used for the prevention of arterial
      thrombosis. However, platelet responsiveness to aspirin is variable among
      individuals and it is important to detect aspirin resistance to improve clinical
      outcome. We analyzed the changes of platelet reactivity before and after aspirin
      treatment. We also investigated the incidence and influencing factors of aspirin
      resistance in Korean. METHODS: We tested platelet function in 198 patients who
      had been treated with aspirin in a Korean university hospital, and 59 of these
      patients were tested for platelet function before and after aspirin treatment. We
      also analyzed platelet reactivity in 136 patients who had not been treated with
      aspirin. Platelet function was tested using the VerifyNow Aspirin Assay
      (Accumetrics, USA). Platelet reactivity was expressed as aspirin reaction unit
      (ARU) and > or =550 ARU was defined as aspirin resistance. RESULTS: Platelet
      reactivity of 136 patients who had not been treated with aspirin was
      632.2plusmn;46.3 ARU (meanplusmn;SD) (range, 462-675). Platelet reactivity of 198
      patients who had been treated with aspirin was 472.5plusmn;60.0 (338-666) ARU,
      and 10.1% of patients were aspirin-resistant. The difference of platelet
      reactivity before and after aspirin treatment was 128.3plusmn;68.7 (-40-248) ARU.
      Hb level was lower and platelet count was higher in aspirin-resistant group than
      in aspirin-sensitive group (P<0.05). CONCLUSIONS: We demonstrated the
      distribution of platelet reactivity before and after aspirin treatment using the
      VerifyNow Aspirin Assay. The incidence of aspirin resistance was 10.1%, and low
      Hb level and high platelet count were related with aspirin resistance.

PMID- 18728373
TI  - [A case of type 2N von Willebrand disease with homozygous R816W mutation of the
      VWF gene in a Nepalese woman].
AB  - Type 2N von Willebrand disease (vWD) can be confused with hemophilia A due to
      decreased factor VIII levels and a bleeding tendency, and differential diagnosis
      is of importance for providing the optimal treatment and genetic counseling. For
      the accurate diagnosis of type 2N vWD, von Willebrand Factor (vWF) function
      tests, multimer assay and gene mutation analysis are needed. The patient was a 38
      yr-old Nepalese woman with a history of bleeding manifestations from childhood,
      such as hemarthrosis, intramuscular hematoma, and menorrhagia. Family history
      revealed that her mother and elder brothers also had bleeding manifestations from
      childhood. When she had a laparotomy in 1991, she was diagnosed as hemophilia A
      with factor VIII level of 3.6% and was transfused with whole blood, factor VIII
      and cryoprecipitates. In June 2007, she was admitted to our hospital for further
      evaluation of bleeding tendency. Blood tests revealed normal CBC; bleeding time,
      2 min; PT, 14.9 sec (11-14 sec); aPTT, 51.2 sec (24-38 sec); and factor VIII,
      4.9% (50-150%). The prolonged aPTT was corrected by 1:1 mixing test to the levels
      of 106% and 84%, respectively, before and after 2 hr-incubation at 37degrees C.
      No abnormalities were found in the vWF antigen level (71.3%), ristocetin cofactor
      assay (130.4%), and multimer assay. Direct DNA sequencing of the VWF gene
      revealed homozygous missense mutation located in exon 19, c.2446C>T
      (p.Arg816Trp), confirming the diagnosis of type 2N vWD.

PMID- 18728374
TI  - Tetrasomy 8 in a patient with acute monoblastic leukemia.
AB  - Trisomy 8 is one of the most frequent numerical chromosomal abnormalities
      observed in hematological malignancies, whereas tetrasomy 8 is a clonal
      aberration seen mainly in myeloid disorders such as acute myelod leukemia (AML)
      and myelodysplastic syndromes. In contrast to trisomy 8, tetrasomy 8 is a rare
      chromosomal aberration, in that only 17 reported AML cases with isolated
      tetrasomy 8 have been documented. Interestingly, the majority of reported cases
      were associated with monocytic-lineage leukemias. According to recent reports,
      tetrasomy 8 is regarded as a poor prognostic factor, and most patients having
      this abnormality relapsed and died within 1 yr. Here, we report a patient with
      acute monoblastic leukemia having tetrasomy 8 and a very aggressive disease
      course.

PMID- 18728375
TI  - [Evaluation of iQ200 automated urine microscopy analyzer].
AB  - BACKGROUND: Microscopic examination of urine sediment is one of the most commonly
      performed tests in the clinical laboratory. However, manual microscopic sediment
      examination is labor-intensive, time-consuming and imprecise. In this study, we
      evaluated the analytical performance and clinical usefulness of a recently
      introduced image-based automated urinalysis system, Iris iQ200 (Iris Diagnostics,
      USA). METHODS: We assessed the iQ200 for linearity, precision and carryover rate
      using patient's samples and quality control materials. On 337 urine samples,
      urine sediment analyses performed by the iQ200 were compared with manual
      microscopy results. RESULTS: The iQ200 showed a good linearity (r2>0.99) for all
      cellular components analyzed. Within-run and total CVs on urine specimens and
      quality control samples were less than 10% except for within-run CV for the
      samples with low concentration of the squamous epithelial cells. The carryover
      rates were 0.21% for RBCs and 1.92% for WBCs. The agreement rates within one
      grade between the iQ200 and manual microscopy for RBCs, WBCs, and squamous
      epithelial cells were 93.8%, 94.2% and 96.9%, respectively. CONCLUSIONS: Since
      the iQ200 showed a reliable analytical performance and good concordance with
      manual microscopy, it could be useful in the clinical practice as a screening
      procedure.

PMID- 18728376
TI  - [Standardized sweat chloride analysis for the diagnosis of cystic fibrosis in
      Korea].
AB  - BACKGROUND: Cystic fibrosis is a chronic progressive autosomal recessive disorder
      caused by the CFTR gene mutations. It is quite common in Caucasians, but very
      rare in Asians. Sweat chloride test is known to be a screening test for the
      cystic fibrosis due to the fact that electrolyte levels in sweat are elevated in
      patients. In this study, sweat chloride levels in Korean population were measured
      and analyzed by using standardized pilocarpine iontophoresis sweat chloride test.
      METHODS: The sweat chloride test was performed in 47 patients referred to Yondong
      Severance Hospital from August, 2001 to April, 2007 and 41 healthy volunteers.
      The sweat chloride tests were conducted according to the CLSI C34-A2 guideline
      using pilocarpine iontophoresis method, and the chloride concentrations in sweat
      were measured by mercurimetric titration. RESULTS: Four patients showed sweat
      chloride concentrations higher than 60 mmol/L. Reference interval was calculated
      as 1.4-44.5 mmol/L by analysis of the results of healthy volunteers (n=41). Four
      patients who exhibited high sweat chloride levels, had characteristic clinical
      features of cystic fibrosis and their diagnoses were confirmed either by repeated
      sweat chloride test or genetic analysis. CONCLUSIONS: Standardized sweat chloride
      test can be utilized as a useful diagnostic tool for cystic fibrosis in Koreans.
      In cases of sweat chloride levels higher than 40 mmol/L, the test should be
      repeated for the possible diagnosis of cystic fibrosis. All the confirmed Korean
      cases of cystic fibrosis showed sweat chloride level above 60 mmol/L.

PMID- 18728377
TI  - [A case of multiple myeloma showing marked differences in serum IgG levels
      between protein electrophoresis and turbidimetry].
AB  - We report a case of multiple myeloma showing marked differences in serum
      Immunoglobulin G (IgG) levels between serum protein electrophoresis and
      turbidimetry. A 47-yr old man was admitted to our hospital due to severe back
      pain and diagnosed as having IgG-kappa type multiple myeloma. Serum protein level
      was 14.4 g/dL at the time of diagnosis. Serum IgG level was 8.5 g/dL by serum
      protein electrophoresis, but 11.6 g/dL by turbidimetry. The patient's clinical
      conditions had improved after receiving VAD (vincristine, adriamycin,
      dexamethasone) and VTD (vincristine, thalidomide, dexamethasone) chemotherapy and
      there were no differences in IgG levels between electrophoresis and turbidimetry
      when serum IgG levels were less than 3.0 g/dL. According to this, we considered
      that both protein electrophoresis and turbidimetry should be needed to quantify
      serum immunoglobulins for diagnosis and follow-up of the patients with monoclonal
      gammopathy.

PMID- 18728378
TI  - [Molecular typing of Staphylococcus aureus isolated from blood on the basis of
      coagulase gene polymorphism and toxin genes].
AB  - BACKGROUND: Coagulase is produced by all strains of Staphylococcus aureus. The 3'
      coding region of the coagulase (coa) gene contains varying numbers of 81 bp
      tandem repeats. S. aureus produces a variety of extracellular protein toxins.
      Here, we typed S. aureus strains isolated from blood by coa gene restriction
      fragment length polymorphism (RFLP) patterns and toxin gene profiles. METHODS: A
      total of 120 strains of S. aureus were isolated from blood cultures during 2003
      2006 at Kangdong Sacred Heart Hospital. The isolates were typed by PCR RFLP
      analysis of the coa gene and by multiplex PCR for detection of genes encoding
      enterotoxins (sea, seb, sec, sed, and see), toxic shock syndrome toxin-1 (tst),
      exfoliative toxins (eta and etb), mecA and femA. RESULTS: All the S. aureus
      strains were classified into 16 types on the basis of coa gene RFLP and could be
      further differentiated into 34 types according to the combined patterns of coa
      gene RFLP and toxin gene profiles. Of 85 methicillin-resistant S. aureus (MRSA)
      strains, 43 (50.6%) and 36 (42.4%) belonged to the RFLP pattern L5 and pattern
      L1, respectively. MRSA strains belonging to pattern L5 frequently carried tst
      (93.0%) or sec gene (81.4%), and strains belonging to pattern L1 frequently
      carried sea (88.9%) or see gene (44.4%). The rate of the pattern L5 in MRSA
      strains increased over the past few years and was higher in intensive care unit
      than in other wards. CONCLUSIONS: We typed S. aureus strains isolated from blood
      on the basis of coa gene RFLP and toxin genes. The strains belonging to coa gene
      RFLP pattern L5 and L1 appeared to be the major types of MRSA isolasted from
      bacteremia and revealed specific toxin gene profiles according to the coa gene
      RFLP patterns.

PMID- 18728379
TI  - [Chlamydia trachomatis antibody in Fitz-Hugh-Curtis syndrome].
AB  - BACKGROUND: Fitz-Hugh-Curtis (FHC) syndrome is inflammation of the liver capsule
      associated with pelvic inflammatory disease. We measured Chlamydia trachomatis
      antibodies in 30 female patients with acute abdominal pain for diagnosis of FHC
      syndrome, and the results were compared with other tests. METHODS: A dual
      polymerase chain reaction was used for the detection of C. trachomatis in the
      cervix, and a micro-immunofluorescence test was performed to measure the antibody
      to C. trachomatis in serum. Cervical specimens were stained with Gram stain and
      cultured on chocolate agar for detection of Neisseria gonorrhoeae, and abdominal
      computed tomography (CT) and pelvic examinations were performed. RESULTS: Of the
      30 patients examined, 19 were diagnosed as having FHC-syndromes and 11 abdominal
      pains without FHC-syndrome. C. trachomatis was detected from one of the five
      patients studied, and no N. gonorrhoeae was isolated from the patients with FHC
      syndrome. High titers of IgG antibody (1:512-1:1,024) to C. trachomatis were
      demonstrated in all patients with FHC-syndrome. The CT scan revealed
      perihepatitis in 14 patients with FHC-syndrome. CONCLUSIONS: All patients with
      FHC-syndrome are associated with C. trachomatis infections, and a high titer of
      C. trachomatis antibody (IgG) is a very useful marker for FHC-syndrome.

PMID- 18728380
TI  - [Evaluation of combination of BACTEC mycobacteria growth indicator tube 960
      system and Ogawa media for mycobacterial culture].
AB  - BACKGROUND: The combined use of liquid media and solid media is recommended for
      mycobacterial culture. We evaluated diagnostic performance of combination of
      BACTEC Mycobacteria Growth Indicator Tube (MGIT; Becton Dickinson, USA) and 2%
      Ogawa media (Korean Institute of Tuberculosis, Korea) for recovery of
      mycobacteria. METHODS: In September 2007, 1,764 specimens from 1,059 patients
      were cultured with MGIT and Ogawa. Acid fast bacilli (AFB) smear was fluorochrome
      stained. The isolates were identified into Mycobacterium tuberculosis (MTB) and
      nontuberculous mycobacteria (NTM) with PCR using Seeplex TB Detection Kit
      (Seegene, Korea). Recovery rate, time to detection (TTD), contamination rate,
      mixed growth rate and species distribution were analyzed. RESULTS: Two hundred
      thirty-five specimens (13.3%) from 165 patients (15.6%) were positive for
      mycobacterial culture. Recovery rates of mycobacteria from the group using both
      media, MGIT only, and Ogawa only were 13.3%, 12.1%, and 7.8%, respectively. While
      MGIT recovered 98.9% of MTB and 79.7% of NTM, Ogawa recovered 65.9% of MTB and
      54.1% of NTM. TTDs of total mycobacteria/MTB/NTM in MGIT and Ogawa were
      10.6/11.4/9.7 days and 31/29/33 days, respectively. MGIT TTDs of total
      mycobacteria/MTB/NTM from AFB-positive specimens were significantly shorter than
      those of AFB-negative specimens; 8.2/9.5/4.4 days vs 11.6/12.7/10.7 days.
      Contamination and mixed growth rate of MGIT were 9.6% and 3.7%. Primary culture
      of Ogawa recovered 1 MTB and 1 NTM among the 170 MGIT-contaminated specimens and
      38 mycobacteria among 66 specimens that showed mixed cultures of MGIT.
      CONCLUSIONS: MGIT warrants sensitive and rapid isolation of mycobacteria.
      However, the combination of MGIT and Ogawa is more desirable to recover
      mycobacteria in the case of contaminations or mixed cultures.

PMID- 18728381
TI  - [A case of Scedosporium apiospermum keratitis confirmed by a molecular genetic
      method].
AB  - A 54-yr-old male, who was treated by chemotherapy for gastric cancer 15 months
      ago, presented to Yongdong Severance Hospital, Seoul, with complaints of pain in
      his right eye caused by a foreign body from the ground in the previous week. He
      had been treated with topical and oral antibacterial in addition to antifungal
      agents, but did not show significant clinical improvement. After a positive
      corneal culture with mold, topical amphotericin B was added to the initial
      regimen. The mold was identified as Scedosporium apiospermum by macroscopic and
      microscopic morphologies and the nucleotide sequences of a fungal PCR product
      showing 99% homology with those of S. apiospermum (EF151349). He recovered with
      good results at 25 days after corneal epithelial debridement. The early diagnosis
      of S. apiospermum keratitis is very important for proper treatment. It is
      recommended that molecular diagnostic methods such as fungal PCR and sequencing
      be done with conventional cultures whenever a fungal infection is suspected.

PMID- 18728382
TI  - [Evaluation of performance and false positivity of Mediace RPR test that uses a
      chemistry autoanalyzer].
AB  - BACKGROUND: We evaluated the performance and false positive rate of Mediace RPR
      test (Sekisui, Japan), a newly introduced nontreponemal test using a chemistry
      autoanalyzer. METHODS: The sensitivity of Mediace RPR test was analyzed using
      sera from 50 patients with syphilis in different stages (8 primary, 7 secondary,
      and 35 latent), 14 sera positive with fluorescent treponemal antibody absorption
      (FTA-ABS) IgM, and 74 sera positive with conventional rapid plasma regain (RPR)
      card test (Asan, Korea) and also positive with Treponema pallidum
      hemagglutination (TPHA) test or FTA-ABS IgG test. The specificity was analyzed on
      108 healthy blood donors. We also performed RPR card test on 302 sera that had
      been tested positive with Mediace RPR test and also performed TPHA or FTA-ABS IgG
      test to analyze the false positive rate of Mediace RPR test. A cutoff value of
      0.5 R.U. (RPR unit) was used for Mediace RPR test. RESULTS: Mediace RPR test on
      syphilitic sera of different stages (primary, secondary, and latent stages) and
      FTA-ABS IgM positive sera showed a sensitivity of 100%, 100%, 82.9% and 100%,
      respectively. Among the 74 sera positive with conventional RPR card test and TPHA
      or FTA-ABS IgG test, 55 were positive with Mediace test. The specificity of
      Mediace RPR test on blood donors was 97.2%. Among the 302 sera positive with
      Mediace RPR test, 137 sera (45.4%) were negative by RPR card and TPHA/FTA-ABS IgG
      tests. CONCLUSIONS: Although the sensitivities of Mediace RPR were good for
      primary and secondary syphilis, due to its high negative rate of Mediace RPR over
      the conventional RPR positive samples, further studies are necessary whether it
      can replace conventional nontreponemal test for screening purpose. Moreover, in
      view of the high false positive rate, positive results by Mediace RPR test should
      be confirmed with treponemal tests.

PMID- 18728383
TI  - [A case of ABO*Ael02/O04 genotype with typical phenotype O].
AB  - Ael is a rare blood type which has the least amount of A antigen among A
      subgroups. It can be detected by special tests performed to resolve the
      discrepancy between red cell and serum typing in routine serological typing. The
      presence of A antigen on Ael red cell is demonstrable only by adsorption and
      elution tests. An Ael individual does not secret A substance in the saliva and
      may have anti-A antibody in the serum which is usually less reactive with the
      reagent red cells than anti-B antibody. In Korea, Ael02 has been reported more
      frequently than other Ael alleles. We report a case of Ael02/O04 who presented as
      typical phenotype O with strong anti-A and anti-B antibodies and no A antigen
      detected even by adsorption and elution tests. The case has been proved to be
      Ael02/O04 by direct sequencing analysis. In individuals with history of
      discrepancies in the results of ABO phenotyping, ABO genotyping is needed for an
      accurate evaluation of their blood type.

PMID- 18728384
TI  - Cleavage of the star strand facilitates assembly of some microRNAs into Ago2
      containing silencing complexes in mammals.
AB  - In animals, microRNAs (miRNAs) and small interfering RNAs (siRNAs) repress
      expression of protein coding genes by assembling distinct RNA-induced silencing
      complexes (RISCs). It has previously been shown that passenger-strand cleavage is
      the predominant mechanism when siRNA duplexes are loaded into Argonaute2 (Ago2)
      containing RISC, while an unwinding bypass mechanism is favored for miRNA
      duplexes with mismatches. Here I present experimental data indicating that some
      mammalian miRNAs are assembled into Ago2-containing RISC by cleaving their
      corresponding miRNA star strands. This phenomenon may depend on the secondary
      structure near the scissile phosphate of the miRNA duplex. In addition, I show
      that ATP is not required for star-strand cleavage in this process. Taken
      together, the data here provide insight into the miRNA-loading mechanisms in
      mammals.

PMID- 18728385
TI  - The effects of p53 on whole organism longevity are mediated by autophagy.
AB  - The tumor suppressor protein p53 has a major impact on organismal aging. Recently
      it has become clear that p53 not only controls DNA damage responses, senescence
      and apoptosis but also plays a major role in the control of autophagy. Thus,
      deletion, depletion, or inhibition of p53 induces autophagy in human, mouse and
      nematode cells. We therefore tested the hypothesis that the mutation of the p53
      orthologue CEP-1 might increase the life span of Caenorhabditis elegans through
      an increase in baseline autophagy. For this, we evaluated the survival of
      nematodes lacking cep-1, alone or in combination with RNA inference with the
      autophagy gene bec-1 (which encodes the orthologue of Atg6/Beclin 1). cep-1
      mutants exhibited a prolonged life span. While BEC-1 depletion during adult life
      did not cause significant modification of the life expectancy of wild type
      controls, it did reduce the increased life span of cep-1 mutants down to
      approximately normal levels. These results indicate that the life span-extending
      effect of the cep-1 mutation is mediated by autophagy. These results lend support
      to the hypothesis that autophagy has a broad positive impact on organismal aging.

PMID- 18728386
TI  - Metformin slows down aging and extends life span of female SHR mice.
AB  - Studies in mammals have led to the suggestion that hyperglycemia and
      hyperinsulinemia are important factors both in aging and in the development of
      cancer. It is possible that the life-prolonging effects of calorie restriction
      are due to decreasing IGF-1 levels. A search of pharmacological modulators of
      insulin/IGF-1 signaling pathway (which resemble effects of life span extending
      mutations or calorie restriction) could be a perspective direction in regulation
      of longevity. Antidiabetic biguanides are most promising among them. Here we show
      the chronic treatment of female outbred SHR mice with metformin (100 mg/kg in
      drinking water) slightly modified the food consumption but decreased the body
      weight after the age of 20 months, slowed down the age-related switch-off of
      estrous function, increased mean life span by 37.8%, mean life span of last 10%
      survivors by 20.8%, and maximum life span by 2.8 months (+10.3%) in comparison
      with control mice. On the other side, treatment with metformin failed influence
      blood estradiol concentration and spontaneous tumor incidence in female SHR mice.
      Thus, antidiabetic biguanide metformin dramatically extends life span, even
      without cancer prevention in this model.

PMID- 18728387
TI  - Budding yeast 14-3-3 proteins contribute to the robustness of the DNA damage and
      spindle checkpoints.
AB  - Cells respond to DNA or mitotic spindle damage by activating specific pathways
      that halt the cell cycle to allow for possible repair. Here, we report that
      inactivation of one of the Saccharomyces cerevisiae 14-3-3 proteins, Bmh1, as
      well as the bmh1-S189P bmh2 mutant, failed to exhibit normal spindle damage
      induced cell cycle delay and conferred hypersensitivity to benomyl or nocodazole.
      These defects were additive with those conferred by the bub2 and mad2 spindle
      checkpoint mutations. Following cdc13-1-induced DNA damage, the 14-3-3 response
      was additive with those provided by the Mec1 (ATR-related)-controlled Rad53 (CHK2
      related) and Chk1 (CHK1-related) checkpoint pathways and also distinct from the
      PKA (Protein Kinase A)-controlled response. Therefore, the budding yeast 14-3-3
      proteins contribute to the robustness of the two major mitotic checkpoints and,
      by doing so, may also ensure optimal coordination between the responses to two
      distinct types of damage.

PMID- 18728388
TI  - Expanding role of cyclin dependent kinases in cytokine inducible gene expression.
AB  - The Positive Transcriptional Elongation Factor b (P-TEFb), a heterodimer of CDK9
      and Cyclin T1, is widely implicated in control of basal gene expression. Here, P
      TEFb is involved in transitioning paused RNA polymerase II to enter productive
      transcriptional elongation mode by phosphorylating negative elongation factors
      and Ser(2) of the heptad repeat in the RNA Pol II COOH terminal domain (CTD).
      This perspective will examine recent work in two unrelated inducible signaling
      pathways that illustrate the central role of P-TEFb in mediating cytokine
      inducible transcription networks. Specifically, P-TEFb has been recently
      discovered to play a key role in TNF-inducible NFkappaB activation and IL-6
      inducible STAT3 signaling. In these signaling cascades, P-TEFb forms protein
      complexes with the activated nuclear RelA and STAT3 transcription factor in the
      cellular nucleoplasm, an association important for P-TEFb's promoter targeting.
      Studies using siRNA-mediated knockdown and/or selective CDK inhibitors show that
      P-TEFb plays a functional role in activation of a subset of NFkappaB-dependent
      targets and all STAT3-dependent genes studied to date. Interestingly, cytokine
      inducible genes that are sensitive to P-TEFb inhibition share an induction
      mechanism requiring inducible RNA Pol II recruitment. Chromatin
      immunoprecipitation studies have preliminarily indicated that this recruitment is
      dependent on CDK enzymatic activity. The potential of inhibiting P-TEFb as an
      anti-inflammatory therapy in innate immunity and systemic inflammation will be
      discussed.

PMID- 18728389
TI  - Mdt1/ASCIZ: a new DNA damage response protein family.
AB  - DNA damage response pathways are crucial for genome stability and prevention of
      cancer and are overall remarkably conserved from yeast to mammals. Two novel DNA
      damage response proteins, yeast Mdt1 (Modifier of DNA damage tolerance 1) and
      human ASCIZ (ATM/ATR-substrate Chk2-interacting Zn(2+)-finger protein), were
      recently identified based on their interactions with the N-terminal FHA domains
      of the conserved checkpoint kinases Rad53 and Chk2, respectively, and ASCIZ was
      subsequently re-isolated as an ATM-interacting protein (ATMIN). Mdt1 and ASCIZ
      share remarkable sequence similarity (36% highly conserved residues, 17%
      identity) and extended SQ/TQ cluster domains (SCDs) typical of DNA damage
      response proteins. However, despite their structural similarities and conserved
      interactions with the checkpoint machinery, the two proteins seem to respond to
      different DNA lesions: the strongest phenotypes of ASCIZ deficiency are increased
      sensitivity to DNA base damaging agents and altered immunoglobulin gene
      diversification following enzyme-induced base damage in B lymphocytes, whereas
      absence of Mdt1 leads to hypersensitivity to 3'-blocked DNA double-strand breaks
      and inefficient recombinational maintenance of telomeres. The Mdt1/ASCIZ family
      may function as structurally related scaffolds that facilitate efficient DNA
      repair, albeit with diverged lesion specificity.

PMID- 18728390
TI  - PI3-K and GSK-3: Akt-ing together with microtubules.
AB  - Phosphoinositide-3-Kinase (PI3-K) and the downstream kinases Akt and Glycogen
      Synthase Kinase-3 (GSK-3) have recently been implicated in regulating both
      microtubule (MT) dynamics and organization. Here we review the role of this
      signalling pathway in controlling MTs, and explore ways in which the kinases and
      their substrates may co-operate to spatially regulate MTs in different contexts.

PMID- 18728391
TI  - A connection between MAPK pathways and circadian clocks.
AB  - Circadian clocks and mitogen-activated protein kinase (MAPK) signaling pathways
      are fundamental features of eukaryotic cells. Both pathways provide mechanisms
      for cells to respond to environmental stimuli, and links between them are known.
      We recently reported that the circadian clock in Neurospora crassa regulates
      daily rhythms in accumulation of phosphorylated, and thus active, OS-2 MAPK, a
      relative of mammalian p38 MAPK, when cells are grown in constant conditions. In
      the absence of acute stress, rhythmically activated MAPK then signals to
      downstream effector molecules to regulate rhythmic expression of target genes of
      the pathway. Clock regulation of MAPK signaling pathways provides a mechanism to
      coordinately control major groups of genes such that they peak at the appropriate
      times of day to provide a growth and survival advantage to the organism by
      anticipating stresses. MAPK pathways are well known for their role in cell
      proliferation and tumor suppression. New evidence reveals that some mammalian
      clock components also function as tumor suppressors and rhythms in phospho-MAPK
      have been observed in higher eukaryotes. Thus, the role of the clock in
      regulation of the activity of MAPK pathways provides important clues into the
      function of the circadian clock as a tumor suppressor.

PMID- 18728392
TI  - Protecting the stress response, guarding the MKP-1 mRNA.
AB  - The RNA-binding protein (RBP) HuR plays a vital role in the mammalian stress
      response, effecting changes in the proliferation and survival of damaged cells.
      HuR prominently influences the stress response by regulating the stability and
      translation of mRNAs encoding stress-response proteins. Recently, HuR was found
      to affect mitogen-activated protein kinase (MAPK) signaling, at least in part by
      post-transcriptionally promoting the expression of MAPK phosphatase-1 (MKP-1). As
      anticipated for a pivotal regulator of the MAPKs c-jun N-terminal kinase (JNK)
      and p38, MKP-1 expression is tightly regulated transcriptionally, post
      transcriptionally and post-translationally. HuR's influence on MKP-1 expression
      helps to ensure the appropriate abundance of MKP-1 and consequently the
      appropriate cellular response to stress stimuli.

PMID- 18728393
TI  - Nek6 is involved in G2/M phase cell cycle arrest through DNA damage-induced
      phosphorylation.
AB  - Nek6 is a recently identified NIMA-related kinase that is required for mitotic
      cell cycle progression. In the present study, we examined the role of Nek6 in the
      DNA damage response. We found that Nek6 is phosphorylated upon IR and UV
      irradiation through the DNA damage checkpoint in vivo. Nek6 is also directly
      phosphorylated by the checkpoint kinases Chk1 and Chk2 in vitro. Notably, Nek6
      activation during mitosis is completely abolished by IR and UV irradiation.
      Moreover, the ectopic expression of Nek6 overrides DNA damage-induced G(2)/M
      arrest. These results suggest that Nek6 is a novel target of the DNA damage
      checkpoint and that the inhibition of Nek6 activity is required for proper cell
      cycle arrest in the G(2)/M phase upon DNA damage.

PMID- 18728394
TI  - An intrinsic checkpoint model for regulation of replication origins.
AB  - A recent paper by Alvino et al., (MCB 2007; 27:6396) challenges the standard
      model of the DNA replication checkpoint. Their work shows that the checkpoint
      does not simply prevent late origins from firing in the presence of the
      nucleotide synthesis inhibitor hydroxyurea; instead it delays origin firing to
      maintain the regular order of origin firing relative to the now much slower rate
      of fork elongation. To explain these results, this perspective proposes a model
      in which the timing of origin firing is intrinsically coupled to the rate of fork
      elongation by the fact that late origins can only fire after early forks have
      terminated and released some essential replisome factor. This coupling fails in a
      checkpoint mutant background because stalled forks disassemble and release
      replisome factors prematurely, allowing for unregulated origin firing.

PMID- 18728395
TI  - Mouse models for BRCA1 associated tumorigenesis: from fundamental insights to
      preclinical utility.
AB  - Germline mutations in BRCA1 result in a significant predisposition for breast and
      ovarian cancer, with frequent LOH of the remaining wild type allele. Soon after
      the identification of BRCA1, several different knockout mice were generated to
      study its biological function in vivo. BRCA1, which is involved in DNA double
      strand break (DSB) repair, appeared to be essential for embryonic proliferation
      and survival during mid-gestation. In contrast to human mutation carriers
      however, heterozygous mouse mutants did not show spontaneous cancer development.
      Therefore, a number of conditional mouse models were developed. while tumors of
      these mice show varying degrees of similarity with their human counterparts, two
      mouse models develop mammary tumors that lack expression of estrogen and
      progesterone receptors and ERBB2. This 'triple negative' signature is a
      characteristic feature of BRCA1-associated breast cancers, which can therefore
      not be treated with endocrine agents or ERBB2-targeting therapeutics. Promising
      drugs for treating BRCA1-mutated tumors include platinum compounds and PARP
      inhibitors, which are specifically toxic to DSB repair deficient cells. Although
      encouraging results have been reported, recent findings indicate that BRCA1/2
      deficient ovarian tumors can escape from such targeted treatment by genetic
      reversion. This resistance mechanism might be studied in future mouse tumor
      models based on Brca1 truncating mutations mimicking defined human founder
      mutations.

PMID- 18728396
TI  - Somatic oncogenic mutations, benign skin lesions and cancer progression: where to
      look next?
AB  - Somatic oncogenic activating mutations in FGFR3 and/or PIK3CA have recently been
      described in benign epithelial cutaneous lesions that never progress to
      malignancy (seborrheic keratoses and epidermal nevi). The same mutations have
      been observed in malignant neoplasms from other tissues (bladder carcinoma,
      cervix cancer, colorectal cancer, myeloma). However, many of the abovementioned
      epithelial benign cutaneous tumors do not harbour mutations in FGFR3 or PIK3CA.
      In this review, we focus on new candidate genes for discovery and we outline the
      potential of the skin as a model to achieve a better understanding of cancer
      biology.

PMID- 18728397
TI  - Usp39 is essential for mitotic spindle checkpoint integrity and controls mRNA
      levels of aurora B.
AB  - Accurate chromosome segregation relies on the mitotic spindle checkpoint. This
      checkpoint acts to restrict ubiquitin ligase activity of the Anaphase-promoting
      complex (APC/C) in mitosis until all chromosomes are bipolarly attached to the
      mitotic spindle. We performed a functional RNAi-based screen to identify De
      ubiquitinating enzymes (Dubs) involved in mitotic progression. We identified
      Usp39 as a new factor required to maintain the spindle checkpoint and support
      successful cytokinesis. Strikingly, although Usp39 clearly contains an ubiquitin
      protease domain, we show that Usp39 is entirely deprived of Dub activity.
      However, consistent wilt a previously described role for Usp39 in mRNA
      processing, we observed specific reduction in Aurora B-mRNA levels after
      depletion of Usp39. Although we find that exogenously expressed Aurora B cDNA is
      not sufficient to rescue the checkpoint defect of Usp39-depleted cells, Aurora B
      expression is restored. Our observations suggest Usp39 to be involved in splicing
      of Aurora B and other mRNAs that are essential for proper spindle checkpoint
      function.

PMID- 18728398
TI  - An evolutionarily conserved leucine-rich repeat protein CLERC is a centrosomal
      protein required for spindle pole integrity.
AB  - The centrosome functions as the microtubule-organizing center (MTOC) and plays a
      vital role in organizing spindle poles during mitosis. The pair of centrioles,
      which are the core components of the centrosome, duplicate once per cell cycle,
      and this feature is essential for the establishment of spindle bipolarity. Here
      we describe the molecular characterization of a novel protein called CLERC
      (Centrosomal leucine-rich repeat and coiled-coil containing protein) which is a
      human ortholog of Chlamydomonas Vfl1 protein. CLERC is a protein of 1032 amino
      acids with a calculated molecular mass of 120 kDa and possesses leucine-rich
      repeat and coiled-coil domains. Database searches revealed that CLERC has
      homologs in a wide variety of eukaryotes and is evolutionarily conserved.
      Endogenous CLERC protein associated with the centrosomes throughout the cell
      cycle and accumulated during mitosis. RNAi-mediated depletion of CLERC blocked
      formation of normal mitotic spindles and led to multipolar spindles. Moreover,
      many of the spindle poles in CLERC depleted cells contained only one centriole,
      indicating that centrosomes split into fractions containing a single centriole.
      These data indicate that the major function of CLERC during mitosis is to
      maintain the structural integrity of centrosomes, thereby contributing to spindle
      bipolarity.

PMID- 18728399
TI  - A role for cGMP-dependent protein kinase II in AMPA receptor trafficking and
      synaptic plasticity.
AB  - Regulated trafficking of AMPA receptors (AMPARs) is an important mechanism that
      underlies the activity-dependent modification of synaptic strength. Trafficking
      of AMPARs is regulated by specific interactions of their subunits with other
      proteins. Recently, we have reported that the AMPAR subunit GluR1 binds the cGMP
      dependent kinase type II (cGKII) adjacent to the kinase catalytic site, and that
      this interaction is increased by cGMP. In this complex, cGKII phosphorylates
      GluR1 at serine 845 (S845), a site known to be phosphorylated also by PKA. S845
      phosphorylation leads to an increase of GluR1 on the plasma membrane. In neurons,
      cGMP is produced by soluble guanylate cyclase (sGC), which is activated by nitric
      oxide (NO). Calcium flux through the NMDA receptor (NMDAR) activates neuronal
      nitric oxide synthase (nNOS), which produces NO. Using a combination of
      biochemical and electrophysiological experiments, we have shown that trafficking
      of GluR1 is under the regulation of NO, cGMP and cGKII. Moreover, our study
      indicates that the interaction of cGKII with GluR1, which is under the regulation
      of the NMDAR and NO, plays an important role in hippocampal plasticity.

PMID- 18728400
TI  - MHC and MHC-like molecules: structural perspectives on the design of molecular
      vaccines.
AB  - Major histocompatibility complex (MHC) molecules bind and present short antigenic
      peptide fragments on the surface of antigen presenting cells (APCs) to T cell
      receptors. Recognition of peptide-MHC complexes by T cells initiates a cascade of
      signals in T cells and activated cells either destroy or help to destroy the APC.
      The MHCs are divided into three subgroups: MHC class I, MHC class II and MHC
      class III. In addition, non-classical MHC molecules and MHC-like molecules play a
      pivotal role in shaping our understanding of the immune response. In the design
      of molecular vaccines for the treatment of diseases, an understanding of the
      three-dimensional structure of MHC, its interaction with peptide ligands, and its
      interaction with the T cell receptor are important prerequisites, all of which
      are discussed herein.

PMID- 18728401
TI  - Group B streptococcal conjugate vaccine: a timely concept for which the time has
      come.
AB  - Invasive disease due to group B Streptococcus (GBS) has been recognized as a
      threat to the health of pregnant women and their infants for almost half a
      century. Development of GBS vaccine candidates has progressed at an exemplary
      pace given lack of sponsorship by manufacturers. A trivalent or pentavalent
      vaccine will be required, and decisions must be made as to the criteria by which
      efficacy will be determined and the population in whom efficacy will be assessed.
      Concerns regarding durability of conjugate vaccine-derived immunity, pregnant
      women as a possible target group and regulatory issues required for licensing
      must be resolved if the prospect of impacting GBS disease burden through
      immunization is to become a reality.

PMID- 18728402
TI  - The suppressor of metastasis Nm23-H1 interacts with the Cdc42 Rho family member
      and the pleckstrin homology domain of oncoprotein Dbl-1 to suppress cell
      migration.
AB  - Tumor invasion and metastasis is regulated by a number of cellular molecules
      known to be involved in signaling and cytoskeletal rearrangement. One of these
      molecules is the suppressor of tumor metastasis Nm23-H1 which linked to
      invasiveness and metastatic potential of human cancers. Nm23-H1 expression is
      down-regulated in human melanoma and invasive breast carcinoma. Recent studies
      have shown an association between the Nm23-H1 and oncoprotein Dbl-1 which is
      associated with guanine exchange and belongs to a family of Guanine Exchange
      Factors (GEF). In this report we show a direct interaction in vitro and in human
      B cells and specifically identified the pleckstrin homology domain of Dbl-1 as
      the domain which binds to Nm23-H1. Furthermore, Nm23-H1 and Dbl-1 colocalized in
      the cytoplasm of COS-7 cells when expressed exogenously and showed predominant
      signals at the periphery of the cells particularly at the plasma membrane.
      Interestingly, Dbl-1 and Cdc42 expression rescued the suppressive activities of
      Nm23-H1 in cell migration assays. We show that Cdc42 a regulatory protein
      involved in cytoskeletal reorganization, cell growth and development can bind to
      Nm23-H1 and the kinase deficient mutant H118F but only weakly to the mutant P96S
      which lacks the ability to suppress cell migration and metastasis. Cdc42 also
      colocalized with Nm23-H1 and the Dbl-1 proteins as specific punctate signals in
      the cytoplasm and at the cell membrane. Nm23-H1 also lead to the reduction in
      membrane ruffles and protuberances when expressed with Dbl-1 and Cdc42.
      Surprisingly, Nm23-H1 interacted with Cdc42 as well as Rac1 but somewhat weaker
      with RhoA. These studies suggests that Nm23-H1 can negatively regulate cell
      migration and tumor metastasis by modulating the activity of Cdc42 and possibly
      other Rho family members through interaction with Dbl-1.

PMID- 18728403
TI  - PBEF1/NAmPRTase/Visfatin: a potential malignant astrocytoma/glioblastoma serum
      marker with prognostic value.
AB  - Malignant astrocytomas comprise anaplastic astrocytoma (AA; grade III) and
      Glioblastoma (GBM; grade IV). GBM is the most malignant with a median survival of
      10-12 months in patients. Using cDNA microarray based expression profiling of
      different grades of astrocytomas, we identified several fold increased levels of
      PBEF1 transcripts in GBM samples. Pre-B-cell colony enhancing factor 1 gene
      (PBEF1) encodes Nicotinamide phosphoribosyltransferase (NAmPRTase), which
      catalyses the rate limiting step in the salvage pathway of NAD metabolism in
      mammalian cells. Further validation using real time RT-qPCR on an independent set
      of tumor samples (n=91) and normal brain samples (n=9), GBM specific higher
      expression of PBEF1 was confirmed. Immunohistochemical staining for PBEF1 on a
      subset of the above samples largely reinforced our finding. We carried out ELISA
      analysis on serum samples of astrocytoma patients to determine whether this
      protein levels would correlate with the presence of tumor and tumor grade. PBEF1
      serum levels were substantially elevated in many of the AA and GBM patients.
      Statistical analysis of these data indicates that in patients with astrocytoma,
      serum PBEF1 levels correlate with tumor grade and is highest in GBM.
      Immunohistochemical analysis of an independent set of 51 retrospective GBM cases
      with known survival data revealed that PBEF1 expression in the tumor tissue along
      with its co-expression with p53 was associated with poor survival. Thus, we have
      identified PBEF1 as a potential malignant astrocytoma serum marker and prognostic
      indicator among GBMs.

PMID- 18728404
TI  - The JNK signaling pathway is involved in sodium-selenite-induced apoptosis
      mediated by reactive oxygen in HepG2 cells.
AB  - Selenium compounds as effective chemopreventive agents can induce apoptosis in
      tumor cells, and reactive oxygen species (ROS) are important mediators in
      apoptosis induced by various stimuli including chemopreventive agents. The major
      mitogen-activated protein kinases (MAPKs), c-JUN N-terminal kinase (JNK), p38 and
      extracelluar signal-regulated kinase (ERK) are three kinases that have been shown
      to regulate apoptosis. In this study, we showed that selenite-induced apoptosis
      in HepG2 cells was mediated by ROS that activated JNK to regulate apoptosis. The
      selenite-treated HepG2 cells showed a dose- and time-dependent decrease in cell
      viability that was coincident with increased the levels of the apoptosis rate.
      The levels of selenite-induced ROS as measured by 2', 7'-dichlorofluorescein
      diacetate (DCFH-DA) fluorescence also showed a dose- and time-dependent increase
      in HepG2 cells. The kinase activity of JNK was induced by selenite in a dose
      dependent manner and HepG2 cells exposed to selenite (10 microM) for 4 h showed
      increased levels of phosphorylated JNK, which decreased when exposed for
      additional 4 h. In contrast, Sp600125, a specific inhibitor of JNK, remarkably
      blocked the apoptosis of HepG2 exposed to selenite. Furthermore, N-acetylcysteine
      (NAC), a known antioxidant, increased cell viability and decreased ROS
      generation. Moreover, NAC effectively blocked apoptosis and decreased the levels
      of phosphorylated JNK induced by selenite. These results revealed that JNK might
      be involved in selenite-induced ROS-mediated apoptosis in HepG2 cells.

PMID- 18728405
TI  - Regenerative medicine: evidence for remarkable healing power of adult (somatic)
      stem cells.

PMID- 18728428
TI  - Toward a virtuous cycle: the changing face of academic health centers.

PMID- 18728429
TI  - "Forward feeding" about students' progress: the case for longitudinal,
      progressive, and shared assessment of medical students.

PMID- 18728430
TI  - "Forward feeding" about students' progress: information on struggling medical
      students should not be shared among clerkship directors or with students' current
      teachers.

PMID- 18728431
TI  - "Forward feeding" about students' progress: more information will enable better
      policy.

PMID- 18728432
TI  - The evolving organizational structure of academic health centers: the case of the
      University of Florida.
AB  - The organizational structures of academic health centers (AHCs) vary widely, but
      they all exist along a continuum of integration--that is, the degree to which the
      academic and clinical missions operate under a single administrative and
      governance structure. This author provides a brief overview of the topic of AHC
      integration, including the pros and cons of more integrated or less integrated
      models. He then traces the evolution of the University of Florida (UF) Health
      Science Center, which was created in the 1950s as a fully integrated AHC and
      which now operates under a more distributed management and governance model.
      Starting as a completely integrated AHC, UF's Health Science Center reached a
      time of maximal nonintegration (or dys-integration) in the late 1990s and at the
      beginning of this decade. Circumstances are now pushing the expanding clinical
      and academic enterprises to be more together as they face the challenges of
      market competition, federal research budget constraints, and reengineering
      clinical operations to reduce costs, enhance access, and improve quality and
      patient safety. Although formal organizational integration may not be possible or
      appropriate for any number of legal or political reasons, the author suggests
      that AHCs should strive for "functional integration" to be successful in the
      current turbulent environment.

PMID- 18728433
TI  - Linking academic and clinical missions: UC Davis' integrated AHC.
AB  - Academic health centers (AHCs) rely on cross-subsidization of education and
      research programs by the clinical enterprise, but this is becoming more
      challenging as clinical reimbursements decline. These new realities provide an
      important opportunity to reevaluate the relationships between medical schools and
      academic medical centers. The authors examine the benefits of their ongoing
      commitment to create a fully integrated AHC at the University of California (UC)
      Davis, discussing strategies that serve as catalysts for continued growth. They
      explore how investments of proceeds from the clinical enterprise directly enhance
      educational and research initiatives, which, in turn, increase the success of
      patient-care programs. This has created a cycle of excellence that leads to an
      enhanced reputation for the entire health system. One strategy involves using
      clinical margins to "prime the pump" in anticipation of major research
      initiatives, resulting in rapid increases in external research funding and
      academic recognition. In turn, this facilitates recruitment of high-quality
      faculty and staff, improving the ability to deliver expert clinical care. The
      overall enhanced institutional reputation positions both the clinical and
      academic programs for further success. The authors posit that such approaches
      require executive-level commitment to a single strategic vision, unified
      leadership, and collaborative financial and operational decision making. Adopting
      such changes is not without challenges, which are discussed, but the authors
      suggest that an integrated AHC fosters optimized operations, enhanced reputation,
      and stronger performance across all mission areas. They also provide examples of
      how the UC Davis Health System has thus attracted philanthropists and investments
      from the private sector.

PMID- 18728434
TI  - The relationship between the University of Pittsburgh School of Medicine and the
      University of Pittsburgh Medical Center--a profile in synergy.
AB  - In the synergistic evolution of their research, educational, and clinical
      programs, the University of Pittsburgh (Pitt) School of Medicine (SOM) and the
      University of Pittsburgh Medical Center (UPMC) have followed one core principle:
      What is good for one is good for both. The collaboration is underpinned by UPMC's
      commitment to its community mission, including support for the academic and
      research objectives of the SOM. UPMC's conceptual origin was fostered by its
      experience with Western Psychiatric Institute and Clinic in the 1970s. Over time,
      UPMC acquired other hospitals through merger and negotiation and, by 2008, had
      grown into a $7 billion global health enterprise. From the outset, the senior
      leaders of both UPMC and Pitt committed to collaborative decision making on all
      key issues. Under this coordinated decision-making model, UPMC oversees all
      clinical activity, including that from a consolidated physicians' practice plan.
      Pitt remains the guardian of all academic priorities, particularly faculty-based
      research. UPMC's steady financial success underpins the model. A series of
      interrelated agreements formally defines the relationship between Pitt and UPMC,
      including shared board seats and UPMC's committed ongoing financial support of
      the SOM. In addition, the two institutions have jointly made research growth a
      priority. The payoff from this dynamic has been a steadily growing Pitt research
      portfolio; enhanced growth, visibility, and stature for UPMC, the SOM, and Pitt
      as a whole; and the sustained success of UPMC's clinical enterprise, which now
      has an international scope. Given the current stagnation in the National
      Institutes of Health budget, the Pitt-UPMC experience may be instructive to other
      academic health centers.

PMID- 18728435
TI  - Teaching and learning moments: BST3 Fisher: artist's statement.

PMID- 18728436
TI  - Science at the interstices: an evolution in the academy.
AB  - Biomedical science is at an evolutionary turning point. Many of the rate-limiting
      steps to realizing the next generation of personalized, highly targeted
      diagnostics and therapeutics rest at the interstices between biomedical science
      and the classic, university-based disciplines, such as physics, mathematics,
      computational science, engineering, social sciences, business, and law.
      Institutes, centers, or other entities created to foster interdisciplinary
      science are rapidly forming to tackle these formidable challenges, but they are
      plagued with substantive barriers, born of traditions, processes, and culture,
      which impede scientific progress and endanger success. Without a more seamless
      interdisciplinary framework, academic health centers will struggle to move
      transformative advances in technology into the foundation of biomedical science,
      and the equally challenging advancement of models that effectively integrate new
      molecular diagnostics and therapies into the business and social fabric of our
      population will be similarly hampered. At the same time, excess attention on
      rankings tied to competition for National Institutes of Health and other federal
      funds adversely encourages academic medical centers (AMCs) and universities to
      hoard, rather than share, resources effectively and efficiently. To fully realize
      their discovery potential, AMCs must consider a substantive realignment relative
      to one another, as well as with their associated universities, as the academy
      looks toward innovative approaches to provide a more supportive foundation for
      the emergent biomedical research enterprise. The authors discuss potential models
      that could serve to lower barriers to interdisciplinary science, promoting a new
      synergy between AMCs and their parent universities.

PMID- 18728437
TI  - The transformation of research in the health professions at the University of
      South Carolina.
AB  - During the past six years, there has been a remarkable transformation of
      research, faculty, and interdepartmental, interinstitutional collaboration in the
      health professions at the University of South Carolina (USC). The author
      describes the context in which this transformation has occurred and the factors
      that caused the USC medical school to move from a position of relative insularity
      from the other colleges within the university--conducting little extramural
      research, and regarding its relationship with its teaching hospitals as distal,
      associated institutions--to a position of full integration into the Division of
      Health Sciences with very significant growth in externally funded research and
      closer-than-ever-before working relationships with its two teaching hospitals.
      The author hopes that the model of interinstitutional collaboration USC is
      developing throughout the region will be thought worthy of emulation elsewhere.
      In this article, the author reviews the transformation of research in the school
      of medicine and the other health professions schools--specifically, nursing,
      pharmacy, public health, and social work--at USC during the past six years. He
      explains how these changes were effected while the school continued to support
      its original mission.

PMID- 18728439
TI  - Supporting the academic mission in an era of constrained resources: approaches at
      the University of Arizona College of Medicine.
AB  - The authors describe initiatives at the University of Arizona College of Medicine
      to markedly expand faculty, build research along programmatic lines, and promote
      a new, highly integrated medical school curriculum. Accomplishing these goals in
      this era of declining resources is challenging. The authors describe their
      approaches and outcomes to date, derived from a solid theoretical framework in
      the management literature, to (1) support research faculty recruitment,
      emphasizing return on investment, by using net present value to guide formulation
      of recruitment packages, (2) stimulate efficiency and growth through incentive
      plans, by using utility theory to optimize incentive plan design, (3) distribute
      resources to support programmatic growth, by allocating research space and
      recruitment dollars to maximize joint hires between units with shared interests,
      and (4) distribute resources from central administration to encourage medical
      student teaching, by aligning state dollars to support a new integrated organ
      system based-curriculum. Detailed measurement is followed by application of
      management principles, including mathematical modeling, to make projections based
      on the data collected. Although each of the initiatives was developed separately,
      they are linked functionally and financially, and they are predicated on
      explicitly identifying opportunity costs for all major decisions, to achieve
      efficiencies while supporting growth. The overall intent is to align
      institutional goals in education, research, and clinical care with incentives for
      unit heads and individual faculty to achieve those goals, and to create a clear
      line of sight between expectations and rewards. Implementation is occurring in a
      hypothesis-driven fashion, permitting testing and refinement of the strategies.

PMID- 18728440
TI  - Strong leadership and teamwork drive culture and performance change: Ohio State
      University Medical Center 2000-2006.
AB  - Several characteristics of academic health centers have the potential to create
      high levels of internal conflict and misalignment that can pose significant
      leadership challenges. In September 2000, the positions of Ohio State University
      (OSU) senior vice president for health sciences, dean of the medical school, and
      the newly created position of chief executive officer of the OSU Medical Center
      (OSUMC) were combined under a single leader to oversee the OSUMC. This mandate
      from the president and trustees was modeled after top institutions with similar
      structures. The leader who assumed the role was tasked with improving OSUMC's
      academic, clinical, and financial performance. To achieve this goal, the senior
      vice president and his team employed the service value chain model of improving
      performance, based on the premise that leadership behavior/culture drives
      employee engagement/satisfaction, leading to customer satisfaction and improved
      organizational performance. Implementing this approach was a seven-step process:
      (1) selecting the right leadership team, (2) assessing the challenges and
      opportunities, (3) setting expectations for performance and leadership behavior,
      (4) aligning structures and functions, (5) engaging constituents, (6) developing
      leadership skills, and (7) defining strategies and tracking goals. The OSUMC
      setting during this period provides an observational case study to examine how
      these stepwise changes, instituted by strong leadership and teamwork, were able
      to make and implement sound decisions that drove substantial and measurable
      improvements in the engagement and satisfaction of faculty and staff; the
      satisfaction of students and patients; and academic, clinical, and financial
      performance.

PMID- 18728441
TI  - The changing face of academic health centers: a path forward for the University
      of Colorado Denver.
AB  - This article describes a decade of major changes at an academic health center
      (AHC) and university. The authors describe two major changes undertaken at the
      University of Colorado and its AHC during the past 10 years and the effects of
      these changes on the organization as a whole. First, the AHC's four health
      professional schools and two partner hospitals were completely relocated from a
      space-limited urban campus to a closed Army base. The impact of that change and
      the management of its potential disruption of academic programs are discussed in
      detail. In the middle of this total relocation, the AHC campus was consolidated
      with a general academic campus within the University of Colorado system,
      compounding the challenge. The authors describe the strategies employed to
      implement this major consolidation, including changing the organizational
      structure and selecting the new name of the university--the University of
      Colorado Denver.

PMID- 18728443
TI  - The changing relationships between academic health centers and their
      universities: a look at the University of Pennsylvania.
AB  - After a period of financial losses in the University of Pennsylvania Health
      System stemming from a combination of internal decision making and negative
      external market forces, the university set out to make substantial changes in the
      governance and administrative organization overseeing its health system and
      medical school. The changes were designed to assure the university and its
      trustees that financial controls were strengthened and that the missions of
      research, education, and patient care were balanced. The governance changes
      included creating a structure whereby a single administrative leader was
      responsible for all three missions--education, research, and clinical care--and
      reported directly to the president of the university. Further, existing governing
      boards responsible for various entities within the school of medicine and health
      system were disbanded, and a new single board was created to oversee PENN
      Medicine, the overarching organization established in 2001 and now responsible
      for oversight of the University of Pennsylvania School of Medicine and the
      University of Pennsylvania Health System. The realignment initiated by these
      major changes spawned additional refinements in leadership responsibilities and
      process controls that, together with the new governance model, are credited with
      financial recovery and stronger performance in all aspects of the enterprise.
      These structural changes led to greater emphasis on integrating and coordinating
      programs to take advantage of PENN Medicine's home in a leading university.

PMID- 18728444
TI  - Case study: the Stanford University School of Medicine and its teaching
      hospitals.
AB  - There is wide variation in the governance and organization of academic health
      centers (AHCs), often prompted by or associated with changes in leadership.
      Changes at AHCs are influenced by institutional priorities, economic factors,
      competing needs, and the personality and performance of leaders. No
      organizational model has uniform applicability, and it is important for each AHC
      to learn what works or does not on the basis of its experiences. This case study
      of the Stanford University School of Medicine and its teaching hospitals--which
      constitute Stanford's AHC, the Stanford University Medical Center--reflects
      responses to the consequences of a failed merger of the teaching hospitals and
      related clinical enterprises with those of the University of California-San
      Francisco School of Medicine that required a new definition of institutional
      priorities and directions. These were shaped by a strategic plan that helped
      define goals and objectives in education, research, patient care, and the
      necessary financial and administrative underpinnings needed. A governance model
      was created that made the medical school and its two major affiliated teaching
      hospitals partners; this arrangement requires collaboration and coordination that
      is highly dependent on the shared objectives of the institutional leaders
      involved. The case study provides the background factors and issues that led to
      these changes, how they were envisioned and implemented, the current status and
      challenges, and some lessons learned. Although the current model is working,
      future changes may be needed to respond to internal and external forces and
      changes in leadership.

PMID- 18728445
TI  - "Dr. Auster and Joan": the problem of asymmetries in terms-of-address.

PMID- 18728447
TI  - Medicine and the arts. Wounds to Heal by Dawn Wood, MD, MPH. Commentary.

PMID- 18728448
TI  - Medical school policies regarding struggling medical students during the internal
      medicine clerkships: results of a national survey.
AB  - PURPOSE: To characterize policies of medical schools regarding struggling medical
      students: those at risk of receiving a grade of less than pass because of
      problems with knowledge, clinical skills, professionalism, or a combination of
      these items. METHOD: The annual 2006 Clerkship Directors in Internal Medicine
      (CDIM) survey included a section about how clerkship directors handle struggling
      third- and fourth-year medical students. The section contained 14 structured
      questions and five items requiring free-text responses. The items explored both
      core and fourth-year clerkship perspectives. Data were analyzed using descriptive
      statistics. RESULTS: Eighty-three of the 110 (76%) institutional members
      responded. Respondents identified 0% to 15% of students as struggling each year
      during the required core internal medicine clerkship and 0% to 11% of fourth-year
      students. Two thirds of respondents present struggling students to a medical
      school promotion committee. More than half (64%) of respondents feel they should
      share information about struggling students with other clerkship directors, and
      51% of respondents do share information. Clerkship directors are divided about
      whether it is in students' best interests to disclose information about them with
      current teachers or other clerkship directors. Only 14% of institutions have
      written policies about sharing information, and 57% of clerkship directors design
      remediation plans for struggling students. CONCLUSIONS: Internal medicine
      clerkship directors handle struggling students in widely varying ways. Many
      clerkship directors share information about struggling students; opinions are
      divided about whether this is appropriate. Future research is needed to determine
      the effectiveness of identifying and remediating struggling students and to
      determine effective remediation plans.

PMID- 18728449
TI  - Establishing policies for the relationship between industry and clinicians:
      lessons learned from two academic health centers.
AB  - The relationship between faculty in academic health centers (AHCs) and commercial
      entities is critically important to improving the public health, yet it may be
      prone to conflicts of interest that adversely affect medical education, research,
      and clinical care. The Association of American Medical Colleges has recently
      recommended that medical schools and AHCs develop policies that better manage and
      occasionally prohibit interactions between academic medicine and industry.
      Because the development of more stringent policies is complex and potentially
      contentious, the author reports the lessons learned from developing new policies
      for the interactions between faculty and industry related to medical education
      and clinical care at Yale School of Medicine and Boston University School of
      Medicine/Boston Medical Center. The content of the policies was strongly
      influenced by the tenets of medical professionalism. Faculty support for new
      policies was strong, an iterative and inclusive process of formulation was
      critical, compromises in content were necessary, and the views of faculty
      concerning industry relationships were complex. After implementation of the new
      policies, the departmental food-related expenses increased, the loss of gifts was
      not appreciably missed, the faculty assumed more responsibility for educating
      trainees on the evaluation of new products, a central repository for receiving
      and evaluating grants from industry was useful, enforcement of the policies has
      been a lingering challenge, and the new policies generated positive publicity.
      Several recommendations are proposed. Creating these policies affirmed the
      importance of an inclusive process, open communication, support of institutional
      leadership, and focus on professional values.

PMID- 18728474
TI  - Methylprednisolone improves lung mechanics and reduces the inflammatory response
      in pulmonary but not in extrapulmonary mild acute lung injury in mice.
AB  - OBJECTIVE: Corticosteroids have been proposed to be effective in modulating the
      inflammatory response and pulmonary tissue remodeling in acute lung injury (ALI).
      We hypothesized that steroid treatment might act differently in models of
      pulmonary (p) or extrapulmonary (exp) ALI with similar mechanical compromise.
      DESIGN: Prospective, randomized, controlled experimental study. SETTING:
      University research laboratory. SUBJECTS: One hundred twenty-eight BALB/c mice
      (20-25 g). INTERVENTIONS: Mice were divided into six groups. In control animals
      sterile saline solution was intratracheally (0.05 mL, Cp) or intraperitoneally
      (0.5 mL, Cexp) injected, whereas ALI animals received Escherichia coli
      lipopolysaccharide intratracheally (10 microg, ALIp) or intraperitoneally (125
      microg, ALIexp). Six hours after lipopolysaccharide administration, ALIp and
      ALIexp animals were further randomized into subgroups receiving saline (0.1 mL
      intravenously) or methylprednisolone (2 mg/kg intravenously, Mp and Mexp,
      respectively). MEASUREMENTS AND MAIN RESULTS: At 24 hrs, lung static elastance,
      resistive and viscoelastic pressures, lung morphometry, and collagen fiber
      content were similar in both ALI groups. KC, interleukin-6, and transforming
      growth factor (TGF)-beta levels in bronchoalveolar lavage fluid, as well as tumor
      necrosis factor (TNF)-alpha, migration inhibitory factor (MIF), interferon (IFN)
      gamma, TGF-beta1 and TGF-beta2 messenger RNA expression in lung tissue were
      higher in ALIp than in ALIexp animals. Methylprednisolone attenuated mechanical
      and morphometric changes, cytokine levels, and TNF-alpha, MIF, IFNgamma, and TGF
      beta2 messenger RNA expression only in ALIp animals, but prevented any changes in
      collagen fiber content in both ALI groups. CONCLUSIONS: Methylprednisolone is
      effective to inhibit fibrogenesis independent of the etiology of ALI, but its
      ability to attenuate inflammatory responses and lung mechanical changes varies
      according to the cause of ALI.

PMID- 18728475
TI  - Finding the hidden target in Pseudomonas aeruginosa management.

PMID- 18728476
TI  - Intensive care unit costs: to infinity and beyond or not?

PMID- 18728477
TI  - Genetic variation, acute lung injury, and Kipling's six honest serving men.

PMID- 18728478
TI  - Gastrointestinal bacterial translocation after fiberoptic bronchoscopy: fact or
      fiction?

PMID- 18728479
TI  - Severe disease manifestations associated with acute chikungunya virus infection.

PMID- 18728480
TI  - Risk factors for short-term mortality from carbon monoxide poisoning treated with
      hyperbaric oxygen.

PMID- 18728481
TI  - "Extracorporeal membrane oxygenation in cardiopulmonary resuscitation: are we
      there yet?".

PMID- 18728482
TI  - A new language of natriuretic peptides in sepsis?

PMID- 18728483
TI  - Is there a hidden benefit associated with early tracheostomy?

PMID- 18728484
TI  - Who let the bugs in?

PMID- 18728485
TI  - Apoptosis of endothelial cells in bacterial sepsis and severe Plasmodium
      falciparum malaria: do we know enough to consider clinical trials?

PMID- 18728486
TI  - Hypertonic resuscitation: is it all in the timing?

PMID- 18728487
TI  - Selective COX-2 inhibitors: new insights into mechanisms of side effects?

PMID- 18728488
TI  - Sepsis-induced myocardial depression and calcium mishandling: an acceptable
      unifying theory?

PMID- 18728489
TI  - A role for heme oxygenase-1 in alveolar repair after wood smoke exposure?

PMID- 18728490
TI  - Serum inflammatory markers after postcardiac arrest resuscitation: surrogate
      markers of efficacy, therapeutic targets, or innocent bystanders.

PMID- 18728491
TI  - Corticosteroids in acute respiratory distress syndrome: back to basics to solve
      the puzzle.

PMID- 18728492
TI  - Perivascular aquaporins: potential postischemic therapeutic drug targets?

PMID- 18728493
TI  - Maintaining cerebral perfusion after polytrauma using arginine vasopressin: a
      classic drug revisited.

PMID- 18728494
TI  - Nitrous oxide: from neurotoxicity to neuroprotection?

PMID- 18728495
TI  - Bad bad blood?

PMID- 18728497
TI  - Four questions for Dr. MacIntyre on his editorial.

PMID- 18728498
TI  - Constipation, critical illness and mortality: gut-derived toxidromes--real and
      now imagined.

PMID- 18728499
TI  - Effect of prone positioning in patients with acute respiratory distress syndrome
      and high Simplified Acute Physiology Score II.

PMID- 18728502
TI  - Anatomical and functional intrapulmonary shunt in acute respiratory distress
      syndrome.

PMID- 18728503
TI  - Anatomical intrapulmonary shunt.

PMID- 18728506
TI  - How "Dear SIRS" and MEDS can help for ED triage.

PMID- 18728507
TI  - Surviving Sepsis Campaign needed consensus to exclude selective decontamination
      of the digestive tract.

PMID- 18728509
TI  - Progress in prevention: new guideline for tobacco use and dependence provides
      arsenal of effective interventions.

PMID- 18728510
TI  - Cardiovascular disease in Chinese women: an emerging high-risk population and
      implications for nursing practice.
AB  - BACKGROUND: Globally, cardiovascular disease (CVD) is the leading cause of death
      among women. In China, the burden of CVD is increasing at an alarming rate; yet,
      it is underestimated and has important primary, secondary, and tertiary
      prevention issues. AIM: This article seeks to document the issues surrounding the
      increased rate of CVD among Chinese women and describe the etiological factors
      and potential strategies to decrease the burden of disease. METHODS: The Medline,
      Current Information in Nursing and Allied Health Literature, Ovid, Science
      Direct, and Government Reports were searched using the key words heart disease,
      cardiovascular, ischemic heart disease, coronary, women, and Chin (China,
      Chinese). Articles were selected if they described epidemiological factors and/or
      interventions to address heart disease in Chinese women. FINDINGS: Rapid
      industrialization and urbanization in China have extended the life expectancy of
      the population, particularly among women. Social, political, and economic factors
      have caused lifestyle changes that have a direct bearing on health. Heart disease
      has become the most common cause of death among Chinese women and the second most
      common cause among men. Paradoxically, prevention and management strategies are
      sparse in relation to the high prevalence. A number of modifiable risk factors
      have been identified as major contributors of CVD and should be a focus of
      primary, secondary, and tertiary prevention. CONCLUSION: Cardiovascular disease
      is already a leading cause of death and disability among Chinese women. The high
      prevalence of risk factors and low rate of awareness, treatment, and control
      signal an urgent need for focusing on this issue in Chinese women. Strategies on
      individual, community, and government levels are recommended. Involving Chinese
      nurses in these strategies is essential.

PMID- 18728512
TI  - Evidence-based practice to assist women in hospital settings to quit smoking and
      reduce cardiovascular disease risk.
AB  - Smoking and obesity are widely recognized cardiovascular risk factors for
      significant morbidity and mortality in women. Although women still smoke less
      than men do, smoking among women is on the increase, especially in younger women
      and teenagers. Reduction of cardiovascular risk through smoking cessation while
      maintaining weight is a major goal of intervention. The purpose of this article
      is to discuss best care practices for women with tobacco addiction using a 3
      point integration of clinical expertise, the best available evidence gained from
      systematic research, and an analysis of satisfaction with care data. A model for
      a smoking cessation intervention with weight management content is presented
      using a conceptual framework of social learning theory, self-efficacy judgments,
      and the 4 principal sources of self-efficacy information. The specific aims of
      this pilot study are to (1) test the feasibility of the study methods and
      procedures, including subject accrual, attrition, and reliability of the
      instruments and protocol; (2) explore utilization of and satisfaction with the
      intervention; and (3) describe the impact of the intervention on primary (smoking
      biomarker) and secondary (weight/body mass index, depression, partner support,
      and smoking cessation self-efficacy temptations) outcomes. Results show that the
      study is feasible, but modifications are needed to improve utilization and
      satisfaction with care. The primary outcome showed a reduction in the smoking
      biomarker while maintaining weight at the 2-month follow-up. There was also
      improvement in skills to manage temptation situations that supported the
      conceptual framework. Hypotheses are presented for a future experimental study.

PMID- 18728513
TI  - Comparison of complications in percutaneous coronary intervention patients
      mobilized at 3, 4, and 6 hours after femoral arterial sheath removal.
AB  - The purpose of this research study was to explore groin complication rates of
      patients mobilized at 3, 4, and 6 hours after femoral arterial sheath removal
      following a percutaneous coronary intervention procedure. Participants were
      recruited from those undergoing coronary angioplasty and coronary stent placement
      at a large public hospital in Brisbane, Queensland. Participants were randomly
      allocated to the 3, 4, or 6 hourly mobilization group. After removal of the
      femoral arterial sheath and again the next day, participants' groins were
      assessed for evidence of complications including hemorrhage, hematoma formation,
      and pseudoaneurysm. The results showed that the length of bed rest after arterial
      sheath removal had no significant effect on bleeding (F 304 = 5.39, P = 0.21) or
      hematoma formation (F 304 = 0.258, P = 0.612) at the groin puncture site for
      participants who mobilized at either 3, 4, or 6 hours after percutaneous coronary
      intervention arterial sheath removal.

PMID- 18728514
TI  - Lipid-lowering therapy today: treating the high-risk cardiovascular patient.
AB  - Diseases of the heart and vascular systems are the leading cause of death in the
      United States and worldwide. High-risk patients have been the focus of lipid
      lowering trials and treatment guidelines, which recognize that more intensive
      reduction of low-density lipoprotein cholesterol is appropriate for a redefined,
      broader high-risk population. Lifestyle modifications and lipid-lowering drug
      therapy form the foundation of primary- and secondary-prevention programs for
      patients at moderate to very high risk. Evidence shows that despite the
      availability of effective agents, such as HMG CoA reductase inhibitors (statins),
      many patients still do not achieve low-density lipoprotein cholesterol goals.
      Nurse-centered case management programs that support early and continued
      adherence with lifestyle and medical therapies have been consistently successful
      at improving the rates of achieving lipid goals in high-risk patients.

PMID- 18728515
TI  - An exploration of the relationship between coronary artery bypass graft patients'
      self-sought educational resources and outcomes.
AB  - Postoperative coronary artery bypass graft (CABG) patients seek educational
      resources around discharge. There is limited research on the type and perceived
      effectiveness of self-sought educational resources. The purpose of this study was
      to describe the use of self-sought educational resources by patients around time
      of discharge and to explore relationships between use of self-sought educational
      resources and self-care knowledge, performance of self-care behavior, and symptom
      frequency. This study is a substudy of a randomized clinical trial that included
      a convenience sample of first-time CABG patients. Significant correlations were
      found between use of self-sought educational resources and greater frequency of
      patient's behavior (P <or= .05), and a decrease in symptom frequency (P <or=
      .05). This study represents a first step toward identifying the association
      between the use of self-sought educational resources after CABG and outcomes
      expected of education.

PMID- 18728516
TI  - The association between early outcome, health-related quality of life, and
      survival following elective open-heart surgery.
AB  - We investigated the impact of perioperative complications on patients' health
      related quality of life (HRQL) and intermediate-term survival after cardiac
      surgery. Improved results for cardiac surgery are well demonstrated in low rates
      of operative mortality and morbidity. However, the association between
      perioperative morbid events, HRQL at 1 year, and survival is unclear. We
      performed a prospective study among 836 elective cardiac surgery patients to
      assess the impact of perioperative outcomes on survival and HRQL at 1 year.
      Health-related quality of life was generated using the 20-item short-form
      questionnaire. Kaplan-Meier and life-table estimates were used to examine the
      relationship of HRQL at 1-year and intermediate-term survival. All HRQL domains
      were statistically improved at 1 year, with the highest gains in general health
      perception (+19.4%) and the least gains in social (+5.1%) and mental (+5.1%)
      domains. Patients experiencing 1 or more perioperative complication or increased
      length of stay reported similar HRQL scores as patients with no complications.
      Patients with negative changes in social (94.5% vs 99.2%, P < .001) and general
      health perception (99.4% vs 95.5%, P < .001) domains showed a reduced survival
      compared with patients with positive HRQL gains at 2 to 5 years after surgery.
      Perioperative complications had minimal or no effect on HRQL at 1 year after
      cardiac surgery.

PMID- 18728517
TI  - Registered nurse initiation of a tobacco intervention protocol: leading quality
      care.
AB  - This article summarizes the development and implementation of a registered nurse
      initiated protocol to intervene with hospitalized patients who are tobacco
      dependent, may be experiencing tobacco withdrawal, and who are hospitalized in a
      smoke-free environment. RATIONALE: Tobacco use is the leading cause of
      preventable death in the United States. Hospitalization provides a unique
      teachable moment to treat tobacco dependence. Nurses can be effective in talking
      with patients about tobacco use. DEVELOPMENT: The clinical nurse specialist
      spheres of influence model and the role of the clinical nurse specialist were
      important for developing a tobacco use intervention protocol. A multi
      disciplinary team created key objectives. These included identifying and
      assessing all patients who use tobacco, providing treatment to manage both
      withdrawal and address tobacco dependence, providing comfort to patients while
      hospitalized in a tobacco-free environment, encouraging lifelong cessation. The
      bedside admitting nurse was chosen as the pivotal professional to trigger tobacco
      use interventions. IMPLEMENTATION: A protocol was finalized that requires the
      bedside nurse to assess all patients for past and current tobacco use. The nurse
      is then prompted to (1) provide information about tobacco dependence and
      treatment, (2) ask if the patient wants nicotine patch therapy to address
      withdrawal and, (3) order a consult with a specialist at the patient's request.
      Extensive and varied educational programs were developed to support the
      implementation of the protocol. OUTCOMES: The tobacco use intervention protocol
      has become important for providing assessment and intervention to patients who
      use tobacco. It has increased the number of specialist consults provided to
      patients. It has increased compliance with quality reporting data by national
      quality accrediting bodies.

PMID- 18728518
TI  - Cardiac rehabilitation coordinators' perceptions of patient-related barriers to
      implementing cardiac evidence-based guidelines.
AB  - BACKGROUND: Coronary heart disease remains the leading cardiovascular cause of
      mortality and morbidity globally. Implementing evidence-based guidelines after a
      coronary event is vital to prevent recurrence of an acute episode. However,
      various barriers to guideline implementation have been identified. OBJECTIVE:
      This article presents the perspective of cardiac rehabilitation (CR) coordinators
      regarding patient-related barriers to implementing the evidence-based guidelines
      after an acute cardiac event. METHODS: Twenty CR coordinators from 4 geographic
      regions of New South Wales, Australia, participated in the study. A
      semistructured interview using open-ended questions was used to obtain the CR
      coordinator's perspectives of the patient-related barriers to guideline
      implementation. Interviews were transcribed, and content analysis was undertaken.
      FINDINGS: The most frequently identified patient-related barriers were (a) coming
      to terms with a diagnosis of heart disease, (b) challenges in changing behavior,
      (c) having heart disease is costly, and (d) other personal barriers. CONCLUSIONS:
      Despite CR coordinators having positive attitudes toward implementing evidence
      based guidelines, several patient-related barriers were identified that
      obstructed the implementation process. The findings have important implications
      for nursing practice in terms of directing efforts at increasing participation in
      CR and engaging commitment of the patient to behavior change. Changes to health
      service policies that address identified barriers could further facilitate the
      provision of evidence-based care to patients with coronary heart disease.

PMID- 18728519
TI  - Endoscopic pneumatic reduction of a pediatric ileo-ileocolic intussusception
      during diagnostic colonoscopy.

PMID- 18728520
TI  - Fellowship training in pediatric gastroenterology in the United States: where are
      we going? Does one size fit all?

PMID- 18728521
TI  - Assessing the validity of clinical trials.
AB  - Clinical trials use scientific methods to evaluate the effectiveness and safety
      of treatments or other interventions. Trials should have both internal and
      external validity, and a well-conducted randomised controlled trial is considered
      to be the most powerful tool for evaluating interventions. Systematic error
      (bias) and random error could threaten the internal validity of trials, and all
      efforts should be made to minimise these in the design, conduct, and analysis of
      studies. Careful attention should be paid to issues such as randomisation,
      allocation concealment, blinding, and sample size. In an internally valid trial,
      external validity refers to the ability of the results to be generalised to the
      "real world" population. Issues to consider in determining the external validity
      of a study include the setting of the trial, the study population, the types of
      interventions used, duration of follow-up, and the types of outcome and how they
      were assessed.

PMID- 18728522
TI  - Frequencies of genetic polymorphisms of TLR4 and CD14 and of HLA-DQ genotypes in
      children with celiac disease, type 1 diabetes mellitus, or both.
AB  - OBJECTIVES: Besides the central role of the adaptive immune system, a disturbance
      of innate immunity is also involved in the pathogenesis of celiac disease (CD).
      Inasmuch as CD and type 1 diabetes mellitus (T1DM) frequently coexist because of
      a common genetic predisposition, our aim was to study the frequency of CD14 C
      260T and TLR4 A+896G single nucleotide polymorphisms (SNPs) and the distribution
      of HLA-DQ genotypes in children affected by CD, T1DM, or both. PATIENTS AND
      METHODS: TLR4 and CD14 SNPs were tested by polymerase chain reaction, followed by
      restriction fragment length polymorphism analysis in 80 children with T1DM, 100
      children with CD, and 47 children with both CD and T1DM. Determination of HLA-DQ
      alleles was done by sequence-specific polymerase chain reaction. Frequencies were
      compared with those of healthy control children. RESULTS: The prevalence of the
      homozygous CD14 C-260TT genotype was significantly (P = 0.0081) lower in children
      with T1DM but not in those with CD and T1DM, compared with control children. No
      difference was found in the genotype and allele frequencies of TLR4 between the
      studied groups. In patients with T1DM, the frequency of the homozygous HLA-DQ8
      genotype was significantly higher than in CD, whereas the frequency of homozygous
      or heterozygous HLA-DQ2 genotypes did not differ from that in control children.
      In patients with CD, both homozygous and heterozygous HLA-DQ2 genotypes were
      significantly more frequent than in the control and T1DM groups, and no elevation
      in the frequency of the HLA-DQ8 genotypes was observed. In patients with T1DM and
      those with CD and T1DM, the occurrence of HLA-DQ2/8 heterozygosity was
      significantly higher than in children with CD only and in control children.
      CONCLUSIONS: Our results suggest that in patients with T1DM, the CD14 C-260TT
      homozygous genotype increases the risk for the development of CD. The
      distribution of HLA-DQ genotype is different in children with CD and T1DM than in
      children with CD or T1DM only. Determination of the HLA-DQ genotype in children
      with T1DM may help in estimating the risk for the development of CD.

PMID- 18728523
TI  - HLA-DQB1*02 dose effect on RIA anti-tissue transglutaminase autoantibody levels
      and clinicopathological expressivity of celiac disease.
AB  - OBJECTIVES: Celiac disease is an autoimmune enteropathy caused by gluten
      ingestion in genetically susceptible individuals. Anti-transglutaminase
      autoantibody (tTGAb) assay is useful to detect candidates undergoing intestinal
      biopsy. Our aim was to investigate whether the DQB1*02 allele could influence
      tTGAb titers and the clinicopathological expressivity of the disease. METHODS: A
      total of 124 patients with celiac disease, tested for RIA tTGAb at diagnosis,
      were typed for HLA-DRB1, -DQA1, and -DQB1 genes and divided according to the
      number of DQB1*02 alleles: group 1, homozygous; group 2, heterozygous; group 3,
      negative. RESULTS: The mean of tTGAb indexes was significantly higher in group 1
      patients than in group 2 (P < 0.02) and group 3 patients (P < 0.01). Patients
      with at least 1 DQB1*02 allele showed more often a typical CD and diffuse
      histological lesions than did patients in the other groups. CONCLUSIONS: The
      study demonstrates that tTGAb titers are HLA-DQB1*02 dose dependent, with
      significantly higher levels in homozygous individuals. Moreover, individuals with
      at least 1 HLA-DQB1*02 allele tend to have a more expressed clinical and
      histological form of celiac disease.

PMID- 18728524
TI  - Immunoglobulin A anti-tissue transglutaminase antibody deposits in the small
      intestinal mucosa of children with no villous atrophy.
AB  - OBJECTIVES: Anti-tissue transglutaminase (anti-TG2) immunoglobulin A (IgA)
      autoantibodies are detectable in the serum of most patients with untreated celiac
      disease (CD). Their deposits in the intestine of patients with CD with severe
      enteropathy are considered specific for this condition. The histological spectrum
      of CD includes cases with normal villous architecture. The aim of this study was
      to look for anti-TG2 IgA deposits in the intestine of children with normal
      villous architecture and to relate them with other markers of gluten sensitivity.
      PATIENTS AND METHODS: A total of 57 children with normal duodenal villous
      architecture and markers of gluten sensitivity were considered. Of those, 39
      showed positive serum anti-endomysium antibodies and/or high levels of anti-TG2
      antibodies (group 1), and 18 were seronegative with only a greater density of
      gammadelta intraepithelial lymphocytes (group 2). Thirty-four children with no
      markers of gluten sensitivity and a normal mucosa represented the control group
      (group 3). The duodenal sections of all patients were investigated for deposited
      anti-TG2 IgA by double immunofluorescence. Human lymphocyte antigen molecular
      typing was performed. RESULTS: In group 1 and in group 2, 33 of 39 children (85%)
      and 12 of 18 children (66%) showed subepithelial anti-TG2 IgA intestinal
      deposits, respectively. Only in 3 of 34 (8.8%) children with no markers of gluten
      sensitivity were anti-TG2 IgA deposits noted. CONCLUSIONS: A subgroup of children
      with no serum CD-associated autoantibodies, but greater density of gammadelta
      intraepithelial lymphocytes, shows a clear anti-TG2 IgA deposition in the
      duodenal mucosa. These children must be investigated further for possible gluten
      sensitivity.

PMID- 18728525
TI  - Rome II versus Rome III classification of functional gastrointestinal disorders
      in pediatric chronic abdominal pain.
AB  - OBJECTIVES: The updated Rome III criteria for pediatric functional
      gastrointestinal disorders (FGIDs) include new FGID categories and changes to the
      Rome II criteria for various FGIDs. To our knowledge, the implications of these
      revisions for patient classification have not been identified. The purpose of
      this study was to compare classification results using Rome II versus Rome III
      criteria for FGIDs associated with chronic abdominal pain. PATIENTS AND METHODS:
      Participants were 368 pediatric patients whose subspecialty evaluations for
      chronic abdominal pain yielded no evidence of organic disease. The children's
      gastrointestinal symptoms were assessed with the parent-report version of the
      Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS). RESULTS: More
      patients met the criteria for a pediatric pain-related FGID according to the Rome
      III criteria (86.6%) than the Rome II criteria (68.0%). In comparison with the
      results from the Rome II criteria, the Rome III criteria classified a greater
      percentage of children as meeting criteria for Abdominal Migraine (23.1% vs 5.7%)
      and Functional Abdominal Pain (11.4% vs 2.7%). Irritable Bowel Syndrome was the
      most common diagnosis according to both Rome II (44.0%) and Rome III (45.1%).
      CONCLUSIONS: Changes to the Rome criteria make the Rome III criteria more
      inclusive, allowing classification of 86.6% of pediatric patients with medically
      unexplained chronic abdominal pain.

PMID- 18728526
TI  - Fructose intolerance in children presenting with abdominal pain.
AB  - OBJECTIVES: We determined the occurrence of fructose malabsorption in pediatric
      patients with previous diagnoses of abdominal pain caused by a functional bowel
      disorder, whether the restriction of fructose intake changes the reporting of
      symptoms, the role of fructose dosage, and the severity of resultant symptoms.
      PATIENTS AND METHODS: We administered a fructose breath test to children
      presenting with persistent unexplained abdominal pain. Patients randomly received
      1, 15, or 45 g fructose, and breath hydrogen was measured for 3 hours after
      ingestion. Test results were positive when breath hydrogen was 20 ppm greater
      than baseline and was accompanied by gastrointestinal symptoms. RESULTS: A total
      of 32 patients was enrolled, and none of the 9 who received 1 g had positive
      results. Three of 10 who received 15 g and 8 of 13 who received 45 g had positive
      results. All patients with positive test results restricted their fructose
      intake. Among the group with positive results, 9 of 11 had rapid improvement of
      their gastrointestinal symptoms. After 2 months, all 9 patients continued to
      report improvement. CONCLUSIONS: We concluded that fructose malabsorption may be
      a significant problem in children and that management of dietary intake can be
      effective in reducing gastrointestinal symptoms.

PMID- 18728528
TI  - Prognosis of chronic or recurrent abdominal pain in children.
AB  - BACKGROUND: Chronic abdominal pain (CAP) or recurrent abdominal pain is common in
      childhood and is rarely associated with organic disease. With modern diagnostic
      technology, new organic abnormalities are found in children with CAP. Thus far a
      causal relation between these abnormalities and CAP has not been established. The
      additional prognostic value of extensive testing of children with CAP is a
      subject of debate. OBJECTIVES: To investigate how often abdominal pain persists
      in children with CAP and to investigate whether medical tests such as laboratory
      tests, imaging, and endoscopy have additional prognostic value to history taking
      and clinical examination. MATERIALS AND METHODS: A systematic search was
      conducted in MEDLINE, EMBASE, and PsycINFO for prospective cohort studies
      published from 1960 until October 2005. The most common medical key words for CAP
      were used in our search strategy. The methodological quality of studies was
      determined. Clinical heterogeneity between studies was analyzed. The percentages
      of children with abdominal pain after follow-up were pooled. RESULTS: The search
      yielded 2620 citations, of which 18 studies met the inclusion criteria. In total,
      1331 children were followed up for 5 years (median, range 1-29 years). In total,
      29.1% (95% CI 28.1-30.2) of patients with CAP had abdominal pain after follow-up.
      The prognosis of CAP diagnosed clinically was similar to that diagnosed after
      additional medical testing. CONCLUSIONS: CAP persisted in 29.1% (95% CI 28.1
      30.2) of children. In the absence of alarming symptoms, additional diagnostic
      testing did not influence the prognosis of CAP.

PMID- 18728529
TI  - Pediatric gastroenterology fellows, class of 2007: how well are they prepared for
      the future?
AB  - OBJECTIVES: Pediatric gastroenterology fellows are expected to acquire skills as
      clinicians, researchers, and educators. An e-mail survey was conducted to examine
      training experiences of individual fellows; to understand how graduating fellows
      rate their abilities as clinicians, researchers, and teachers; and to answer
      whether the size of a pediatric gastroenterology training program affects a
      fellow's training and future position choice. MATERIALS AND METHODS: A survey was
      e-mailed to 76 third-year pediatric gastroenterology fellows. Respondents were
      ranked according to the size of their training program. RESULTS: Completed
      surveys were returned by 50 respondents. Of these, 75% planned to pursue careers
      in academic medicine and 16% in private practice. In all, 68% of trainees
      participated in some type of basic research and 64% in clinical research. As
      attending physicians, 22% of fellows hoped to conduct basic science research and
      74% clinical research. The majority thought they were competent or proficient
      teachers, and rated themselves as advanced beginners or competent when asked to
      evaluate their research skills. The North American Society for Pediatric
      Gastroenterology, Hepatology, and Nutrition recommends that fellows perform 100
      colonoscopies, 20 liver biopsies, and 5 paracenteses to be considered competent.
      We found that regardless of program size, 48% of fellows performed fewer than 100
      colonoscopies, 62% performed fewer than 20 liver biopsies, and 80% performed
      fewer than 5 paracenteses. CONCLUSIONS: The majority of fellows will pursue
      academic careers. Trainees may not be performing sufficient numbers of
      procedures. The number of procedures performed during fellowship was independent
      of program size.

PMID- 18728527
TI  - Relation between clinical symptoms and experimental visceral hypersensitivity in
      pediatric patients with functional abdominal pain.
AB  - OBJECTIVE: The association between clinical symptoms and laboratory visceral
      sensitivity remains poorly defined and controversial. It has even been suggested
      that laboratory observations of visceral sensitivity are irrelevant to the
      clinical presentation of chronic visceral pain. To better understand this
      association, gastrointestinal and psychological features of pediatric patients'
      clinical presentation were examined in relation to a laboratory-based measure of
      visceral sensitivity. PATIENTS AND METHODS: At the time of their medical
      evaluation, 101 patients with medically unexplained abdominal pain (ages 8-15
      years) completed validated questionnaires assessing recent depressive symptoms,
      functional disability, pain efficacy beliefs, gastrointestinal (GI), and non-GI
      symptoms. These clinical features were examined in relation to visceral
      sensitivity assessed 2 months later in the laboratory. The measure of visceral
      sensitivity was based on increases in GI complaints in response to the water load
      symptom provocation task. RESULTS: More severe GI symptoms and functional
      disability in the weeks before patients' clinical evaluation were associated with
      significantly greater increases in GI symptoms in the laboratory in response to
      the water load symptom provocation task (all P < 0.04). Patients believing that
      they had the ability to alleviate their pain (high problem-focused pain efficacy)
      had significantly lower laboratory visceral sensitivity (P < 0.01). Clinical
      depressive symptoms and non-GI symptoms were not associated with laboratory
      visceral sensitivity. CONCLUSIONS: Clinical presentations of more severe GI
      symptoms and disability as well as low perceived pain efficacy are significant
      predictors of laboratory visceral sensitivity in children with functional
      abdominal pain. Depression does not account for the association between clinical
      presentation of GI symptoms and a laboratory measure of visceral sensitivity.

PMID- 18728530
TI  - High incidence and allelic homogeneity of Wilson disease in 2 isolated
      populations: a prerequisite for efficient disease prevention programs.
AB  - OBJECTIVES: Herein we report the results of mutation-based screening for Wilson
      disease (WD) in 2 isolated populations of Sardinia and the Greek island of
      Kalymnos. PATIENTS AND METHODS: Mutation analysis was performed in 110 and 9 WD
      families originating respectively from Sardinia and Kalymons using single-strand
      conformation polymorphism and sequencing methods. In Sardinia, a limited
      screening was performed for -441/-427del in 5290 newborns, whereas in Kalymnos
      397 newborns underwent mutation screening for H1069Q and R969Q using appropriate
      methods. RESULTS: In Sardinia, mutation analysis showed the presence of 6
      mutations accounting for 85% of chromosomes, 1 of which (-441/-427del) is present
      in 61.7% of alleles. The screening for -441/-427del in 5290 newborns revealed the
      presence of 122 heterozygotes, which is equal to an allelic frequency of 1.15%.
      Assuming the same distribution of WD mutations in the general Sardinian
      population, we also inferred an allelic frequency of 0.77% for mutations other
      than -441/-427del, which accounts for an overall frequency of any WD mutation of
      1.92%. Assuming Hardy-Weinberg equilibrium, these data could be translated into a
      WD incidence of 1 in 2707 live births. In Kalymnos, mutation analysis in 9 WD
      families revealed the presence of only 2 mutations. The screening of 397 newborns
      revealed the presence of 18 heterozygotes for H1069Q, 9 for R969Q, and 1 compound
      heterozygote for these mutations, which is equal to an allele frequency of 3.7%.
      Assuming Hardy-Weinberg equilibrium, the expected carrier rate is 7%.
      CONCLUSIONS: These data indicate the need for health education for WD prevention
      in these isolated populations.

PMID- 18728531
TI  - Secular and seasonal trends in obesity in Chilean preschool children, 1996-2004.
AB  - OBJECTIVES: Chile is a unique example of the nutrition transition, with
      improvements in undernutrition and subsequent rapid increases in obesity
      occurring at a rate much faster than in other countries. This study aims to
      describe the cross-sectional obesity trends in Chilean preschool children from
      1996 to 2004. MATERIALS AND METHODS: Anthropometric measurements from preschool
      children (ages 2-5) registered in the Junta Nacional de Jardines Infantiles
      program from 1996 to 2004 were analysed. The weight-for-height z score using the
      World Health Organization 1977/1985 reference curves for age, sex, height, and
      weight were defined to estimate overweight and obesity. The overall trends in
      obesity were described for each study year and generalized estimating equation
      models were used to describe trends in obesity after adjusting for the correlated
      nature of repeated measurements in individual children in consecutive years.
      RESULTS: The prevalence of obese and overweight children has remained constant in
      both boys and girls during the past 9 years; however, after adjustment for
      repeated measurements in individual children, the odds of obesity increased by
      30% each year (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.27-1.31, P <
      0.001). Furthermore, the odds of obesity were significantly greater in both
      August and November compared with March. CONCLUSIONS: The prevalence of obesity
      in Chilean preschool children continues to be a major public health concern, and
      cross-sectional trends may underestimate the magnitude of the problem.

PMID- 18728532
TI  - Compliance with gluten-free diet in children with coeliac disease.
AB  - OBJECTIVES: Coeliac disease (CD) is a lifelong disorder with gluten-induced
      manifestations in different organs. Gluten-free diet (GFD) is required to achieve
      remission and prevent complications; however, study reports on GFD growth effect
      are not consistent. METHODS: Compliance with GFD was estimated according to
      current body mass and height; presence of anaemia and other signs and symptoms;
      and attitude toward GFD. RESULTS: Seventy-one patients with CD (mean age = 12
      years; mean age after CD diagnosis = 9 years) were examined and their blood
      sampled for determination of endomysial antibodies (EMA), haemoglobin, and red
      blood cell count. Questionnaire analysis revealed 42 (59.1%; 4 EMA positive)
      patients to be on strict GFD, 19 (26.8%; 5 EMA positive) were taking small
      amounts of gluten, and 10 (14.1%; all EMA positive) were not on a diet at all.
      The patients on strict GFD had greatest body height, yet the difference was not
      significant. These patients also had a higher mean body mass (P = 0.05) and
      significantly higher mean haemoglobin and mean cell haemoglobin levels (P = 0.05
      and P < 0.05, respectively). Apart from chronic fatigue in patients on partial
      diet (P = 0.05), patient groups did not differ significantly in the frequency of
      symptoms. Anaemia and delayed puberty were recorded only in noncompliers (P <
      0.01 and P < 0.05, respectively). Noncompliers often found the specific diet to
      pose a major life burden (P < 0.01) and did not visit a gastroenterologist on a
      regular basis (P < 0.01). CONCLUSIONS: Almost half of the coeliac patients were
      likely to abandon GFD without experiencing major symptoms, thus increasing the
      risk for developing complications later in life. An active attitude is required
      in the follow-up of patients with CD.

PMID- 18728533
TI  - Mandarin juice improves the antioxidant status of hypercholesterolemic children.
AB  - BACKGROUND: Oxidative stress has been linked to such degenerative diseases as
      atherosclerosis, and it has been suggested that increased dietary intake of
      antioxidants may reduce its progression. OBJECTIVE: To determine the effect of
      mandarin juice consumption on biomarkers related to oxidative stress in
      hypercholesterolemic children. MATERIALS AND METHODS: The diet of 48 children
      with plasma cholesterol >200 mg/dL and low-density lipoprotein cholesterol >130
      mg/dL was supplemented for 28 days with 500 mL/day of pure (100%) mandarin juice
      (Citrus clementina Hort. ex Tan.). The composition of the mandarin juice was
      analyzed, and its antioxidant antiradical activity was evaluated in vitro.
      Malondialdehyde, carbonyl groups, vitamins E and C, erythrocyte-reduced
      glutathione, and plasma lipids were measured at the onset and at the end of the
      supplementation period. The paired Student t test was used to compare values
      before and after supplementation. RESULTS: Mandarin juice exerted a strong
      antioxidant effect mainly due to its high hydroxyl activity and, to a lesser
      extent, to its superoxide scavenger activity. At the end of the study, levels of
      the plasma biomarkers of oxidative stress were significantly decreased
      (malondialdehyde -7.4%, carbonyl groups -29.1%, P < 0.01), whereas the plasma
      antioxidants vitamin E and C (13.5%, P < 0.001 and 68.2%, P < 0.00001,
      respectively) and intraerythrocyte glutathione level (36.7%, P < 0.00001) were
      significantly increased. Plasma lipids and antibodies to oxidized low-density
      lipoproteins remained unchanged. CONCLUSIONS: Regular ingestion of mandarin juice
      significantly reduces plasma biomarkers of lipid and protein oxidation and
      enhances the antioxidant status of consumers.

PMID- 18728534
TI  - Adiponectin and insulin resistance in childhood obesity.
AB  - OBJECTIVES: To measure adiponectin serum levels in Greek children and adolescents
      and correlate them with body fat and insulin resistance. PATIENTS AND METHODS:
      Forty-six obese prepubertal children (19 M, 27 F) and 34 obese adolescents (17 M,
      17 F) ages 9.33 +/- 1.57 and 13.6 +/- 1.42 years, respectively, and 43 matched
      control individuals were studied. Body mass index standard deviation score and
      percent body fat were measured by bioelectric impedance analysis. Fasting indices
      of insulin resistance (HOMA-IR and fasting glucose-to-insulin ratio) were
      calculated for all participants. Indices of insulin resistance derived from oral
      glucose tolerance tests were estimated in obese participants. Adiponectin was
      measured by enzyme-linked immunosorbent assay. RESULTS: (MEAN +/- SD)::
      Adiponectin serum levels were significantly lower in obese participants than in
      nonobese participants (8.11 +/- 3.80 vs 11.81 +/- 4.98 microg/mL, P < 0.001), in
      obese children than in nonobese children (8.86 +/- 3.86 vs 13.08 +/- 5.48
      microg/mL, P < 0.001), in obese adolescents than in nonobese adolescents (7.04 +/
      3.43 vs 10.47 +/- 4.10 microg/mL, P = 0.002), and in obese adolescent boys than
      in obese adolescent girls (5.87 +/- 3.52 vs 8.31 +/- 3.16 microg/mL, P = 0.042).
      There were significant correlations between adiponectin and age, body mass index,
      body mass index standard deviation score, homeostasis model assessment for
      insulin resistance, and fasting glucose-to-insulin ratio. Adiponectin correlated
      with percent body fat after adjustment for sex. Adiponectin correlated
      significantly with several indices of insulin resistance, such as the areas under
      the curves for glucose and insulin, whole-body insulin sensitivity index, glucose
      120', and insulin 30', in obese participants. CONCLUSIONS: Adiponectin was
      significantly lower in obese participants than in nonobese participants in
      general, and it correlated significantly with fasting indices of insulin
      resistance and with indices derived from oral glucose tolerance tests. It is
      worthwhile to further investigate the option of applying a simple measurement of
      serum adiponectin as a screening tool before applying more time-consuming
      techniques in young obese individuals.

PMID- 18728535
TI  - A novel homozygous SLC26A3 nonsense mutation in a Tyrolean girl with congenital
      chloride diarrhea.

PMID- 18728536
TI  - Ischemic hepatitis is a risk factor for progression of liver disease associated
      with parenteral nutrition in intestinal failure.

PMID- 18728537
TI  - Recurrent acute pancreatitis associated with propionic acidemia.

PMID- 18728538
TI  - Lipoma as a pathological lead point in a child with ileocolic intussusception.

PMID- 18728539
TI  - Influence of protein and energy intakes on body composition of formula-fed
      preterm infants after term.
AB  - The aim of the present study was to evaluate changes in body composition in 48
      preterm infants in relation to protein and energy intakes from term up to 3
      months of corrected age, using air displacement plethysmography. Protein intake
      (grams per kilogram per day) was negatively associated with percentage of fat
      mass at 1 month of corrected age. The high-protein-intake group showed greater
      gain in lean body mass gain than did the low-protein-intake group. This finding
      suggests that during the first month of corrected age, high protein intake
      results in a significantly different weight gain composition.

PMID- 18728540
TI  - North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition
      consensus statement on the diagnosis and management of cyclic vomiting syndrome.
AB  - Cyclic vomiting syndrome (CVS) is a disorder noted for its unique intensity of
      vomiting, repeated emergency department visits and hospitalizations, and reduced
      quality of life. It is often misdiagnosed due to the unappreciated pattern of
      recurrence and lack of confirmatory testing. Because no accepted approach to
      management has been established, the task force was charged to develop a report
      on diagnosis and treatment of CVS based upon a review of the medical literature
      and expert opinion. The key issues addressed were the diagnostic criteria, the
      appropriate evaluation, the prophylactic therapy, and the therapy of acute
      attacks. The recommended diagnostic approach is to avoid "shotgun" testing and
      instead to use a strategy of targeted testing that varies with the presence of 4
      red flags: abdominal signs (eg, bilious vomiting, tenderness), triggering events
      (eg, fasting, high protein meal), abnormal neurological examination (eg, altered
      mental status, papilledema), and progressive worsening or a changing pattern of
      vomiting episodes. Therapeutic recommendations include lifestyle changes,
      prophylactic therapy (eg, cyproheptadine in children 5 years or younger and
      amitriptyline for those older than 5), and acute therapy (eg, 5-hydroxytryptamine
      receptor agonists, termed triptans herein, as abortive therapy, and 10% dextrose
      and ondansetron for those requiring intravenous hydration). This document
      represents the official recommendations of the North American Society for
      Pediatric Gastroenterology, Hepatology and Nutrition for the diagnosis and
      treatment of CVS in children and adolescents.

PMID- 18728541
TI  - Mediastinal lymph nodes in patients with non-small cell lung cancer: preliminary
      experience with diffusion-weighted MR imaging.
AB  - OBJECTIVES: The purpose of our study was to describe our preliminary experience
      of evaluating mediastinal lymph node metastases with diffusion-weighted magnetic
      resonance (MR) imaging in patients with non-small cell lung cancer. MATERIALS AND
      METHODS: Forty-two consecutive patients with non-small cell lung cancer underwent
      preoperative diffusion-weighted MR imaging using a non-breath-hold short
      inversion time inversion recovery-echo planar imaging sequence with a high b
      value of 1000 s/mm2. An experienced thoracic radiologist prospectively evaluated
      each study for mediastinal lymph node metastases on a per-patient basis. On
      diffusion-weighted MR imaging, mediastinal lymph node metastasis was defined as a
      focus of low signal intensity at the site of a visible lymph node on
      corresponding T2-weighted image. The MR results were correlated with
      histopathologic findings. RESULTS: Diffusion-weighted MR imaging demonstrated
      mediastinal lymph node metastasis in 4 (80%) of 5 patients with pathologically
      proven metastasis and accurately identified 36 (97%) of 37 patients without
      mediastinal lymph node metastasis. Thus, 40 (95%) of 42 patients were accurately
      diagnosed. The sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy of diffusion-weighted MR imaging for mediastinal
      lymph node metastasis were 80%, 97%, 80%, 97%, and 95%, respectively.
      CONCLUSIONS: Our preliminary results show that diffusion-weighted MR imaging has
      a high negative predictive value for excluding mediastinal lymph node metastases
      from non-small cell lung cancer and has the potential to be a reliable
      alternative non-invasive imaging method for the preoperative staging of
      mediastinal lymph node in patients with non-small cell lung cancer.

PMID- 18728542
TI  - Granulomatous-lymphocytic interstitial lung disease associated with common
      variable immunodeficiency: CT findings.
AB  - PURPOSE: To evaluate computed tomography (CT) scans of individuals with
      granulomatous-lymphocytic interstitial lung disease and common variable
      immunodeficiency (CVID) to determine if there are imaging features that
      distinguish this manifestation of CVID from the more usual imaging findings.
      MATERIALS AND METHODS: A review of the CVID population at our institution
      identified a series of 5 patients with CVID who had documented granulomatous
      disease on biopsy specimens. The initial and follow-up CT examinations were
      reviewed by 2 radiologists, and imaging findings in the chest and abdomen were
      tabulated by consensus. In addition, a pathologist reviewed histopathologic
      specimens and clinical presentations and therapeutic interventions were obtained
      from patient charts. RESULTS: In all, 5/5 patients (100%) had widespread
      pulmonary micronodules with a lower lung zone predominance, 4/5 (80%) had smooth
      interlobular septal thickening with mid to lower lung zone predominance, 1/5
      (20%) had mild bronchiectasis, 4/5 (80%) had multifocal pulmonary consolidation,
      5/5 (100%) had thoracic or abdominal lymphadenopathy, 2/5 (40%) had hepatomegaly,
      5/5 (100%) had splenomegaly, 1/5 (20%) had nonspecific hypoattenuating splenic
      lesions, and 2/5 (40%) had nonspecific hypoattenuating renal lesions. The
      pulmonary nodules and lymphadenopathy commonly tended to wax and wane in severity
      over time, and more marked disease was often associated with areas of focal
      consolidation. CONCLUSION: Granulomatous-lymphocytic interstitial lung disease,
      which can occur in patients with CVID, presents with CT findings distinct from
      the usual airway abnormalities most commonly associated with CVID.

PMID- 18728543
TI  - Systemic to pulmonary venous shunt: imaging findings and clinical presentations.
AB  - Multislice computed tomography technology has enabled sophisticated insights into
      the evaluation of collateral venous pathways in the thorax. A small but well
      established body of literature has described the multiple venous pathways in
      patients with central venous obstruction. In unusual circumstances, however,
      physiologically maladaptive pathways have been described involving systemic to
      pulmonary venous shunts. This paper describes 21 patients with systemic to
      pulmonary venous shunts having a wide spectrum of etiologies. Clinical
      presentations typically include cardiopulmonary symptomatology and paradoxical
      emboli. Ultrafast magnetic resonance and multislice computed tomography
      established the diagnosis of this uncommon but important entity.

PMID- 18728544
TI  - Rebound thymic hyperplasia after pneumonectomy and chemotherapy for primary
      synovial sarcoma.
AB  - Thymic hyperplasia occurs in a small proportion of patients receiving
      chemotherapy for various malignancies. It likely results from an immunologic
      rebound phenomenon. Fluorodeoxyglucose positron emission tomography-computed
      tomography is an important tool for staging malignant neoplasms. We report a case
      of rebound thymic hyperplasia manifesting as a hypermetabolic mass on
      fluorodeoxyglucose positron emission tomography-computed tomography after
      pneumonectomy and chemotherapy for primary pulmonary synovial sarcoma. We
      highlight the importance of recognizing the phenomenon of rebound thymic
      hyperplasia, as it can mimic residual or recurrent malignancy, especially in the
      setting of altered chest anatomy.

PMID- 18728545
TI  - Immune-reconstitution syndrome related to atypical mycobacterial infection in
      AIDS.
AB  - The immune-reconstitution syndrome is a paradoxical inflammatory response to a
      preexisting or a coexisting disease, after the initiation of highly active
      antiretroviral therapy for the human immunodeficiency virus. Infrequently
      described, the radiographic and computed tomographic findings of the immune
      reconstitution syndrome, which is related to the Mycobacterium avium
      intracellulare infection and to highly active antiretroviral therapy, are
      presented in 2 patients. Homogeneous mediastinal and hilar lymphadenopathy were
      present in both individuals, with one having a large mass accompanied by small
      nodules.

PMID- 18728546
TI  - Giant pulmonary hamartoma.
AB  - A 61-year-old woman presented with dyspnea and intense cough. Chest radiography
      showed opacity of the entire left hemithorax and computed tomography of the chest
      confirmed a solid heterogeneous mass extending from apex to base, with foci of
      calcification and areas of low attenuation. Left upper lobe resection was
      performed, removing the tumor in large pieces. Histologic characteristics of the
      lesion were compatible with typical hamartoma. No signs of recurrence were
      detected 2.5 years after the operation.

PMID- 18728547
TI  - Inflammatory myofibroblastic tumor of the lung: recurrence after steroid
      treatment.
AB  - We report a case of a patient with inflammatory myofibroblastic tumor of the
      lung, which recurred after steroid treatment. The diagnosis of the tumor was
      confirmed by a core needle lung biopsy and pathology. The patient was initiated
      on steroid therapy, which on complete response was slowly tapered and
      discontinued. Few months later, the patient presented with dyspnea again. Chest
      radiography and computed tomography scans depicted recurrence at the tumor
      resection site in the right lobe of lung and a new tumor in the left lower lobe.
      Restarting the steroid therapy, led to regression of the tumors at both sites.
      This is a rare case of inflammatory myofibroblastic tumor recurring poststeroid
      therapy and adds to the current clinical knowledge about this peculiar
      manifestation of this disease entity.

PMID- 18728548
TI  - Neurofibromatosis type 1 with tracheobronchial neurofibromas: case report with
      emphasis on tomographic findings.
AB  - A 65-year-old man with neurofibromatosis type 1 (NF-1) presented with a 3-month
      history of dyspnea and cough. The chest spiral computed tomography scan showed
      multiple neurofibromas in the larynx and tracheobronchial tree. Bronchoscopy was
      performed and the biopsy confirmed the diagnosis of benign neurofibroma. The
      upper airway involvement in NF-1 is rare, and the diagnosis on the basis of the
      clinical manifestation may be difficult. The clinical manifestations of patients
      with tracheobronchial neurofibromas are mostly related to airway obstruction,
      presenting with cough, wheezing, and dyspnea. Our case illustrates the value of
      spiral computed tomography imaging in providing an excellent anatomic definition
      of this rare manifestation of NF.

PMID- 18728549
TI  - Multiple mycotic aneurysms of the pulmonary arteries resolving with conservative
      management: multislice CT examination findings.
AB  - Mycotic pulmonary artery aneurysms are rare but potentially fatal complications
      of infective endocarditis. Three mycotic aneurysms developed in a 22-year-old
      female patient who had a history of intravenous drug use. She suffered from
      Staphylococcus aureus pneumonia and infective endocarditis. The patient was
      managed conservatively with antibiotics. She did not have hemoptysis during a
      prolonged hospital stay. Several multislice computed tomography examinations were
      performed to follow these aneurysms over a period of 19 months. The 2 smaller
      aneurysms had resolved by 9 weeks postdevelopment. The largest aneurysm was
      stable at 9 weeks and was smaller at 19 months, but it had not yet completely
      resolved. The literature on this rare condition was reviewed and its prognosis
      and management were discussed.

PMID- 18728550
TI  - Absence of the left brachiocephalic vein with venous return through the left
      superior intercostal vein: CT findings.
AB  - Asymptomatic congenital thoracic venous anomalies are becoming clinically more
      relevant with the increasing utilization of minimally invasive surgical vascular
      procedures, such as left-sided implantable cardioverter defibrillator
      implantation. The purpose of this report is to describe the computed tomography
      findings of the congenital absence of the left brachiocephalic vein in a patient
      with no evidence of congenital cardiovascular disease and no prior history of
      central venous instrumentation. In this patient, the left internal jugular and
      the left subclavian veins drain via the left superior intercostal vein, the
      accessory hemiazygous, the hemiazygous, and the azygous vein into the right
      brachiocephalic vein to form the superior vena cava. The clinical significance
      and possible embryogenesis of this anomaly are discussed.

PMID- 18728551
TI  - Left-sided cervical aortic arch associated with pseudocoarctation, aneurysm
      formation, and anomalous left brachiocephalic vein: appearance on MDCT and MR
      angiography.
AB  - Cervical aortic arch (CAA) is a rare congenital aortic anomaly. It can be
      associated with several cardiovascular abnormalities including aortic aneurysm,
      valvular disease, and pseudocoarctation. In this report, we present a case of CAA
      with combined association of both aneurysm formation and pseudocoarctation. This
      combination of anomalies is extremely uncommon, described in only 4 cases in the
      literature. In addition, our patient had an anomalous subaortic left
      brachiocephalic vein that, to our knowledge, was not previously described in the
      literature to be associated with CAA. The radiographic, multidetector computed
      tomography scan, and magnetic resonance angiography imaging findings are
      presented.

PMID- 18728552
TI  - CT findings of bronchial glandular papilloma.
AB  - Solitary pulmonary papillomas are rare benign tumors in adults. Glandular
      papilloma is the rarest subtype among them. In this report, we describe a case of
      glandular papilloma that showed unique computed tomography features. It was a
      round nodule containing air spaces encapsulated with a smooth and thin wall,
      which suggested its endobronchial origin and a secondary change owing to air
      trapping.

PMID- 18728553
TI  - Diffuse periairway thickening in patients with Mikulicz disease.
AB  - A 70-year-old woman presented with dry mouth, bilateral swelling of the eyelids,
      and abnormal taste and smell sensations that had persisted for 3 years. She was
      diagnosed with Mikulicz disease and presented with dyspnea on exertion
      afterwards. Chest computed tomography and magnetic resonance imaging showed wall
      thickening of the trachea and bilateral bronchus. Transbronchial needle
      aspiration showed lymphoproliferative lesion in the tracheobronchus. The patient
      was treated with corticosteroid, which improved all of her clinical symptoms,
      computed tomography, and magnetic resonance findings. In this case, we presented
      a rare condition of coexistent Mikulicz disease with tracheobroncial wall
      thickening caused by lymphoproliferation without lesions in small airways or
      lung.

PMID- 18728554
TI  - Incidental cardiac and pericardial abnormalities on chest CT.
AB  - OBJECTIVE: Although there has been an increasing interest in diagnosing cardiac
      and pericardial diseases using electrocardiogram-gated cardiac computed
      tomography (CT), radiologists tend to neglect or overlook many incidentally
      detected abnormalities on conventional, nongated chest CT. The objective of this
      study is to describe the imaging appearance and clinical significance of such
      cardiac or pericardial diseases. CONCLUSIONS: Recognition and detection of
      various cardiac and pericardial abnormalities on chest CT as the evaluation of
      noncardiac disease is important for its early diagnosis and proper management.

PMID- 18728556
TI  - Pituicytoma: case report.
AB  - OBJECTIVE: Pituicytoma is a rare but distinct low-grade glioma of the
      neurohypophysis. To date, we have found only 28 cases reported in the literature
      and have reviewed these in addition to our own case to delineate the clinical
      implications of this relatively recently defined tumor. CLINICAL PRESENTATION: A
      71-year-old woman presented with bitemporal hemianopsia and was found to have a
      large sellar tumor, resembling a pituitary adenoma. Transsphenoidal resection was
      attempted but was complicated by significant tumor vascularity. Pathology at that
      time was interpreted as a "granular cell tumor." The patient was then referred to
      our institution for management of the residual tumor. INTERVENTION: The patient
      underwent preoperative embolization to decrease tumor vascularity, and subtotal
      tumor resection was performed via a craniofacial approach. Postoperatively, the
      patient has enjoyed significantly improved visual fields despite residual tumor.
      No adjuvant treatment was given. There has been no regrowth of the residual
      tumor, as shown on magnetic resonance imaging, over a follow-up period of 1.5
      years. The final pathological diagnosis was pituicytoma. CONCLUSION: Pituicytomas
      are benign, slow-growing tumors that seem to be cured by gross total resection.
      The role of radiation therapy is controversial. We advocate an aggressive
      surgical approach with possible preoperative embolization to reduce the
      vascularity of the tumor.

PMID- 18728557
TI  - Clinical implications of the infratentorial rosette-forming glioneuronal tumor:
      case report.
AB  - OBJECTIVE: This article describes our experience with two patients who presented
      with unusual tumors in the cerebellar vermis and cerebral aqueduct. Although
      sparing the fourth ventricle proper, both tumors had histological features
      consistent with the rare diagnosis of a rosette-forming glioneuronal tumor of the
      fourth ventricle, of which only 19 cases have been reported previously. A review
      of the clinical features and courses of all 21 cases is presented and management
      recommendations are given. CLINICAL PRESENTATION: Patient 1 was a 42-year-old man
      who presented with a headache of 1 day's duration and no neurological signs, in
      whom magnetic resonance imaging disclosed a nonenhancing mass lesion occupying
      the proximal cerebral aqueduct. Patient 2 was a 38-year-old woman with a long
      history of intermittent giddiness, no neurological signs, and a magnetic
      resonance imaging scan that demonstrated a nonenhancing and subtle abnormality in
      the cerebellar vermis. INTERVENTION: Biopsy was performed on both lesions, the
      first endoscopically and the second via craniotomy. The only postoperative
      complication was short-lived double vision and poor upgaze in Patient 1.
      CONCLUSION: These cases demonstrate that the rosette-forming glioneuronal tumor
      may be more accurately categorized as an infratentorial tumor rather than a tumor
      of the fourth ventricle. Because the literature indicates that this is a tumor
      with little potential for malignant behavior and considerable morbidity can
      accompany attempts at resection, a conservative management approach would seem
      well advised. If this tumor is to be managed conservatively, because of the
      paucity of extended follow-up data, long-term radiological and clinical
      surveillance is strongly recommended.

PMID- 18728558
TI  - Curvularia fungi presenting as a large cranial base meningioma: case report.
AB  - OBJECTIVE: Fungal infections are emerging as a growing threat to human health,
      especially in immunocompromised patients. Candida, Cryptococcus, and Aspergillus
      are a few of the commonly encountered organisms leading to brain abscesses. In
      this report, we describe Curvularia geniculata as the causative agent in central
      nervous system infection. CLINICAL PRESENTATION: Our review of the literature did
      not reveal a similar published case of central nervous system infection with this
      organism. A 35-year-old African-American man presented with obstructive
      hydrocephalus from a large cranial base lesion. Imaging characteristics on
      computed tomographic and magnetic resonance imaging scans were consistent with
      those of a cranial base meningioma. INTERVENTION: The patient underwent an
      endoscopic transnasal/transclival approach to the anterior middle cranial base
      for biopsy and decompression of this lesion. A spindle cell proliferation was
      observed on frozen section, which favored a diagnosis of meningioma. However, on
      permanent sections, we identified fungal hyphae with budding. Subsequent biopsies
      grew Curvularia in fungal cultures. Deoxyribonucleic acid sequencing was used to
      confirm the identification of the isolate as Curvularia geniculata. CONCLUSION:
      Limited data are available for in vitro susceptibility testing of Curvularia, and
      treatment modalities have not yet been standardized. The prognosis is usually
      poor. Despite being treated with voriconazole and intravenous amphotericin, this
      patient progressed to multiorgan failure and ultimately died. This is the first
      reported case of central nervous system infection by Curvularia geniculata.

PMID- 18728559
TI  - Transient inhibition of motor function induced by the Cavitron ultrasonic
      surgical aspirator during brain mapping.
AB  - OBJECTIVE: We report, for the first time, the occurrence of interference between
      a Cavitron ultrasonic surgical aspirator (CUSA) and intraoperative brain mapping
      performed by direct electrical stimulation (DES). METHODS: Intraoperative
      polygraphic recordings (electrocorticogram and electromyogram) were gathered from
      a 44-year-old patient harboring a recurrent Grade II oligoastrocytoma operated on
      with the aid of a CUSA and DES. RESULTS: Simultaneous use of CUSA and DES at the
      subcortical level in proximity to the corticospinal tract brought about the
      abolition of previously evident motor responses. This abolition was fully
      reversible after the CUSA was turned off. An analogous pattern of motor response
      inhibition was evident when the DES was applied cortically and the CUSA was used
      subcortically close to motor pathways. Interestingly, the authors had already
      observed a similar phenomenon in many patients when the CUSA was used for
      resection of lesions located within or in proximity to subcortical language
      pathways. In this setting, the CUSA induced transient speech disturbances that
      were confirmed afterwards by the DES. This interference with language and motor
      mapping might be interpreted as a transitory inhibition of axonal conduction.
      CONCLUSION: The clinical significance of this interference is relevant when the
      CUSA and DES are used simultaneously for motor mapping because the CUSA can
      decrease the sensitivity of the brain mapping technique. Further studies will be
      required to determine the neurophysiological mechanism underlying this
      interference.

PMID- 18728560
TI  - Stent-mediated wedging of a calcific embolus to recanalize an occluded middle
      cerebral artery: technical case report.
AB  - OBJECTIVE: Calcific cerebral emboli are rare yet pose a difficult therapeutic
      challenge because of their lack of response to thrombolytic therapy and their
      propensity for fragmentation. CLINICAL PRESENTATION: A 75-year-old woman
      developed aphasia and hemiparesis after cardiac catheterization from a near
      occlusive calcific embolus to the left middle cerebral artery origin. The
      calcific embolus was shown to be hemodynamically limiting by computed tomographic
      perfusion and diffusion-weighted magnetic resonance imaging. INTERVENTION: The
      patient was treated medically for 6 days with anticoagulation, antiplatelet, and
      hypertensive therapies but continued to deteriorate. A decision was made to
      attempt retrieval of the calcific embolus. Conventional intracranial mechanical
      clot and coil retrieval systems were used initially but were unsuccessful and
      caused migration of the calcific embolus, leading to complete occlusion of the
      left middle cerebral artery origin. At this point, the decision was made to wedge
      the calcific embolus against the vessel wall. A balloon-mounted coronary stent
      was used to achieve this successfully, resulting in recanalization of the middle
      cerebral artery trunk and flow restoration. CONCLUSION: Symptomatic calcific
      emboli, which are poorly responsive to pharmacological therapy and difficult to
      recover using conventional retrieval systems, may be treated by immobilization
      against the vessel wall using a balloon-mounted stent.

PMID- 18728563
TI  - Analysis of the hemodynamic characteristics of brain arteriovenous malformations
      using electrical models: baseline settings, surgical extirpation, endovascular
      embolization, and surgical bypass.
AB  - OBJECTIVE: The goal of this report is to analyze the hemodynamic characteristics
      of low- and high-flow arteriovenous malformations (AVM) using computerized
      electrical models. METHODS: Two electrical models of brain AVMs were created.
      These models consist of electrical resistors that simulate AVM vessels. In both
      models, a low-flow AVM and a high-flow AVM, the flow of electrons simulates the
      flow of blood. RESULTS: Using the models, it was possible to analyze the pressure
      and flow patterns in the nidus of the small, low-flow AVM and in the nidus of the
      large, high-flow AVM. Baseline hemodynamic "physiological" conditions of the two
      AVMs were studied. With the models, it was also possible to assess the AVM
      hemodynamic changes (in the feeding arteries, in the various parts of the nidus,
      and in the draining veins) after surgery, after embolization, and after surgical
      bypass of the malformation. The role of autoregulation in the three treatment
      modalities was also assessed. CONCLUSION: These electrical models seem to be
      useful in simulating and studying the behavior of flow and pressure in the
      different parts of the AVM nidus (arterial, arteriolar, arteriolar-venular,
      venular, venous) before and after treatment. The models can also be used to
      devise and simulate new treatment strategies that might lead to improved
      treatment of these highly complex vascular malformations of the brain.

PMID- 18728564
TI  - Treatment of giant middle cerebral artery aneurysms with a flow replacement
      bypass using the excimer laser-assisted nonocclusive anastomosis technique.
AB  - OBJECTIVE: To define the clinical value of the flow replacement bypass using the
      excimer laser-assisted nonocclusive anastomosis (ELANA) technique in the
      treatment of patients with a noncoilable, nonclippable giant intracranial
      aneurysm of the middle cerebral artery (MCA). METHODS: Between 1999 and 2006, 22
      patients with a giant intracranial aneurysm of the MCA were treated in our
      hospital with an ELANA flow replacement bypass and MCA occlusion. We collected
      data on patient characteristics, operative aspects, complications, and functional
      health scores using the modified Rankin Scale. Mean follow-up was 3.6 years
      (range, 0.2-7.7 yr). RESULTS: We were able to construct a patent bypass in 20
      (91%) of 22 patients. All 34 ELANA attempts resulted in a patent anastomosis with
      a strong backflow directly after ELANA catheter retraction. The patients did not
      need to undergo temporary occlusion in any of the ELANA constructions. Mean +/-
      standard deviation intracranial-to-intracranial bypass flow was 53 +/- 13 ml/min.
      MCA aneurysm treatment was attempted in all 20 patients who had a patent bypass
      and was successful in 19 of them. There was a fatal hemorrhagic complication in
      one patient (5%), a nonfatal hemorrhagic complication in three patients (14%),
      and a nonfatal ischemic complication in six patients (27%). At follow-up, 17
      patients (77%) had a functionally favorable outcome (modified Rankin Scale score
      at follow-up was the same as or less than the preoperative modified Rankin Scale
      score). All of these patients were independent at follow-up (modified Rankin
      Scale score < or =2). CONCLUSION: This study demonstrates satisfactory results in
      the treatment of giant MCA aneurysms with an ELANA flow replacement bypass,
      considering the very grave natural history and treatment complexity of these
      lesions. The ELANA technique is a useful tool in the treatment armamentarium of
      the vascular neurosurgeon.

PMID- 18728565
TI  - Angiographic patterns of Wingspan in-stent restenosis.
AB  - OBJECTIVE: A classification system developed to characterize in-stent restenosis
      (ISR) after coronary percutaneous transluminal angioplasty with stenting was
      modified and applied to describe the appearance and distribution of ISR occurring
      after Wingspan (Boston Scientific, Fremont, CA) intracranial percutaneous
      transluminal angioplasty with stenting. METHODS: A prospective, intention-to
      treat, multicenter registry of Wingspan treatment for symptomatic intracranial
      atherosclerotic disease was maintained. Clinical and angiographic follow-up
      results were recorded. ISR was defined as greater than 50% stenosis within or
      immediately adjacent (within 5 mm) to the implanted stent(s) and greater than 20%
      absolute luminal loss. ISR lesions were classified by angiographic pattern,
      location, and severity in comparison with the original lesion treated. RESULTS:
      Imaging follow-up (3-15.5 months) was available for 127 intracranial stenotic
      lesions treated with Wingspan percutaneous transluminal angioplasty with
      stenting. Forty-one lesions (32.3%) developed either ISR (n = 36 [28.3%]) or
      complete stent occlusion (n = 5 [3.9%]) after treatment. When restenotic lesions
      were characterized using the modified classification system, 25 of 41 (61.0%)
      were focal lesions involving less than 50% of the length of the stented segment:
      three were Type IA (focal stenosis involving one end of the stent), 21 were Type
      IB (focal intrastent stenosis involving a segment completely contained within the
      stent), and one was Type IC (multiple noncontiguous focal stenoses). Eleven
      lesions (26.8%) demonstrated diffuse stenosis (>50% of the length of the stented
      segment): nine were Type II with diffuse intrastent stenosis (completely
      contained within the stent) and two were Type III with proliferative ISR
      (extending beyond the stented segment). Five stents were completely occluded at
      follow-up (Type IV). Of the 36 ISR lesions, 16 were less severe or no worse than
      the original lesion with respect to severity of stenosis or length of the segment
      involved; 20 lesions were more severe than the original lesion with respect to
      the segment length involved (n = 5), actual stenosis severity (n = 6), or both (n
      = 9). Nine of 10 supraclinoid internal carotid artery ISR lesions and nine of 13
      middle cerebral artery ISR lesions were more severe than the original lesion.
      CONCLUSION: Wingspan ISR typically occurs as a focal lesion. In more than half of
      ISR cases, the ISR lesion was more extensive than the original lesion treated in
      terms of lesion length or stenosis severity. Supraclinoid internal carotid artery
      and middle cerebral artery lesions have a propensity to develop more severe
      posttreatment stenosis.

PMID- 18728566
TI  - Limitations of magnetic resonance imaging and magnetic resonance angiography in
      the diagnosis of intracranial aneurysms.
AB  - OBJECTIVE: Magnetic resonance imaging (MRI) and magnetic resonance angiography
      (MRA) are being used with increasing frequency for the diagnosis of intracranial
      aneurysms. Although the literature suggests that MRI and MRA are accurate, we
      have observed that both are associated with a high likelihood of false-positive
      results in the diagnosis of aneurysms. We prospectively evaluated and compared
      the accuracy of MRI/MRA versus digital subtraction angiography (DSA) for the
      diagnosis of intracranial aneurysms. METHODS: Over the course of 2 years, 133
      patients diagnosed with one or more unruptured intracranial aneurysms by MRI/MRA
      were prospectively evaluated in an outpatient setting. The patients were advised
      to undergo cerebral four-vessel DSA, and the results from DSA were compared with
      MRI/MRA findings. RESULTS: In 59% of cases, the DSA and MRI/MRA findings were
      markedly different. Specifically, in 38% of MRI/MRA-positive cases, DSA findings
      were completely normal, showing no aneurysms. In an additional 21% of cases,
      although DSA confirmed the presence of an aneurysm, it differed substantially
      from MRI/MRA findings in terms of aneurysm location, number of aneurysms, or
      aneurysm type. In general, the false-positive aneurysms by MRI/MRA were smaller
      than 5 mm and were most commonly identified in the anterior communicating artery
      region. CONCLUSION: MRI/MRA studies are often inaccurate in the diagnosis of
      intracranial aneurysms and should not be used as the sole diagnostic studies for
      intracranial aneurysms. Other radiographic modalities should be further
      investigated as alternatives to MRI/MRA for the diagnosis of intracranial
      aneurysms.

PMID- 18728567
TI  - Endoscopic endonasal resection of anterior cranial base meningiomas.
AB  - OBJECTIVE: The endonasal route may be feasible for the resection of anterior
      cranial base tumors that abut the paranasal sinuses. There are several case
      reports and mixed case series discussing this approach. Other than pituitary
      adenomas, there is a lack of literature describing the outcomes of endonasal
      approaches for single-tumor types such as meningiomas. METHODS: In this study, we
      describe our current endoscopic endonasal technique and demonstrate the
      feasibility of using it to access anterior cranial base meningiomas from the back
      wall of the frontal sinus to the sella and laterally to the region of the
      midorbit. After this discussion, which includes key technical considerations and
      nuances, we address safety and efficacy by reporting the outcomes of our early
      experience with endoscopic endonasal resection of 35 anterior cranial base
      meningiomas. RESULTS: A total of 35 patients underwent endoscopic endonasal
      resection of anterior cranial base meningiomas from October 2002 to October 2005.
      Degree of resection by tumor location was as follows: 10 of the 12 (83%) patients
      with olfactory groove meningiomas planned for complete resection underwent gross
      total (seven of 12) or near-total (>95%) (three of 12) resection (67% of all 15
      olfactory tumors); 12 of 13 patients (92%) with tuberculum meningiomas underwent
      gross (11 of 13) or near (>95%) (one of 13) total resection; five patients
      diagnosed with petroclival meningiomas had successful resection of the parasellar
      portion of their tumors with relief of visual symptoms (no patients underwent
      complete resection of their tumors via the endoscopic, endonasal approach); two
      giant petroclival meningiomas were debulked with 63 and 89% resection,
      respectively.All patients experienced resolution or improvement of visual
      symptoms. No patient experienced permanent worsening of vision after surgery.
      Only one (3%) patient without preoperative endocrine dysfunction experienced a
      new, permanent pituitary deficit, diabetes insipidus. One (3%) patient
      experienced a new neurological deficit after experiencing a hemorrhage 3 weeks
      after surgery. The postoperative cerebrospinal fluid leak rate was 40% (14 of 35)
      and varied by tumor location. All leaks were resolved without craniotomy. There
      were no cases of bacterial meningitis. One patient developed a superinfection of
      a sterile granuloma from a sinusitis 2 years after surgery. There were two cases
      of deep venous thrombosis and one pulmonary embolus. There were no operative or
      perioperative deaths. CONCLUSION: Cranial base meningiomas can be successfully
      managed via a purely endoscopic endonasal approach with acceptable morbidity and
      mortality rates. The extent of resection is guided by patient factors and
      symptoms, not by approach. This series had a high cerebrospinal fluid leak rate.
      With the evolution of new reconstruction techniques, these rates have been
      substantially reduced.

PMID- 18728568
TI  - Extent of surgical resection of malignant astrocytomas of the spinal cord:
      outcome analysis of 35 patients.
AB  - OBJECTIVE: The optimal management of malignant intramedullary spinal cord
      astrocytomas remains controversial. Although radiotherapy has become the standard
      of care, the relationship between extent of resection and survival remains
      unclear. We report the outcomes of the surgical management of 35 malignant spinal
      cord astrocytomas and assess the association of extent of resection with survival
      after aggressive resection of these tumors. METHODS: An institutional
      intramedullary spinal cord tumor database (1990-2002) was reviewed to identify
      all patients treated for malignant astrocytomas of the spinal cord (anaplastic
      astrocytoma [AA] or glioblastoma multiforme [GBM]). Length of survival from
      surgery was charted by Kaplan-Meier plots, and association of extent of resection
      with survival was assessed via log rank analysis for stratified covariates and
      Cox proportional-hazards model for continuous covariates. RESULTS: Twenty-seven
      (77%) and eight (23%) patients underwent resection of AA and GBM, respectively.
      Mean age was 29 +/-16 years (range, 2-61 yr). Tumor involved six +/- four
      vertebral levels. For AA cases, radical resection (no residual postoperative
      magnetic resonance enhancement) was achieved in 12 (44%) patients and subtotal
      resection (residual postoperative magnetic resonance enhancement) was achieved in
      15 (56%). No GBM patients underwent radical resection (mean estimated resection,
      70%). After surgery, two (6%) patients improved neurologically by modified
      McCormick score, 19 (54%) remained stable, and 14 (40%) declined. Median overall
      survival for AA patients was 72 months (85% at 1 yr; 59% at 5 yr). Median overall
      survival for GBM patients was 9 months (31% at 1 yr; 0% at 5 yr). Subtotal versus
      radical resection of AA was associated with decreased overall survival (38 versus
      78% at 4 yr, P = 0.028). Postoperative tumor dissemination was associated with
      decreased survival (P = 0.004). When adjusting for multiple comparisons (P <
      0.006 needed for significance), a trend of increased survival was observed with
      radical resection (P = 0.023). CONCLUSION: Neurological function can be preserved
      with aggressive resection of malignant intramedullary spinal astrocytomas;
      however, motor decline may be observed in many cases. Radical resection of AA was
      associated with a trend of increased overall survival in nondisseminated AA
      cases. Radical surgery and radiotherapy of GBM was associated with poor survival,
      similar to historical controls of diagnostic biopsy and radiotherapy. A markedly
      shorter survival may be expected in cases in which AA disseminates along the
      neuraxis. Biopsy alone may not provide the best outcomes for patients with
      malignant spinal cord tumors.

PMID- 18728569
TI  - Endoscopic third ventriculostomy in idiopathic normal pressure hydrocephalus: an
      Italian multicenter study.
AB  - OBJECTIVES: The aim of the report is to define the indications and results of
      endoscopic third ventriculostomy (ETV) in idiopathic normal pressure
      hydrocephalus and to discuss the physiopathological mechanism of this procedure.
      METHODS: The cases of 110 patients with idiopathic normal pressure hydrocephalus
      who underwent ETV in four Italian neurosurgical centers were retrospectively
      reviewed. The postoperative outcome was correlated with patient age, length of
      clinical history, preoperative clinical score, symptoms of clinical onset, type
      of hydrocephalus, and intraoperative findings. RESULTS: The follow-up period
      ranged from 2 to 12 years (average, 6.5 yr). The outcome evaluation was made 2
      years after the procedure. Postoperative clinical improvement occurred in 76
      (69.1%) of 110 patients. There was no correlation between success rate and
      patient age or type of ventricular enlargement (normal or enlarged fourth
      ventricle). Conversely, the rate of neurological improvement was higher in
      patients with shorter clinical history, better preoperative neurological score,
      and clinical onset with gait disturbances. Moreover, the intraoperative finding
      of the sudden reappearance of normal cerebral pulsations and significant downward
      and upward movements of the third ventricular floor after ETV was also correlated
      with a good outcome. CONCLUSION: ETV results in a relatively high rate of
      clinical improvement and a low complication rate in patients with idiopathic
      normal pressure hydrocephalus. Therefore, it may be easily performed with the
      same approach used for intracranial pressure monitoring with low morbidity.
      However, our data must be confirmed by additional studies.

PMID- 18728570
TI  - Lower incidence of reoperation with longer shunt survival with adult
      ventriculoperitoneal shunts placed for hemorrhage-related hydrocephalus.
AB  - OBJECTIVE: The incidence of reoperation for ventriculoperitoneal shunts (VPS) in
      adults, although lower than in pediatric patients, is not insignificant. We
      hypothesize that adult VPS placed for hemorrhage-related hydrocephalus have a
      lower incidence of reoperation than those placed for other types of
      hydrocephalus. METHODS: We retrospectively reviewed all adult (>/= 20 yr) VPS
      initially placed from February 2001 to August 2006 at the University of Florida.
      We determined the incidence and time interval to reoperation. Follow-up was
      conducted by telephone interview and review of medical records. RESULTS: A total
      of 286 adult VPS were initially placed: 96 (34%) hemorrhage and 190 (66%)
      nonhemorrhage. A total of 15 (16%) hemorrhage patients underwent 22 shunt
      reoperations, compared with 50 (27%) nonhemorrhage patients who underwent 82
      shunt reoperations (P = 0.0316). A Poisson regression analysis of the number of
      reoperations, factoring hemorrhage, age, and sex, demonstrated a significantly
      lower incidence of reoperation in hemorrhage patients (P = 0.0900). A Cox
      proportional hazards model analysis of time to first reoperation, factoring
      hemorrhage, age, and sex, demonstrated a significantly longer shunt survival in
      hemorrhage patients (P = 0.0404). CONCLUSION: Adult VPS placed for hemorrhage
      related hydrocephalus have a significantly lower incidence of reoperation and
      significantly longer shunt survival. This result may be related to an incidence
      of transient shunt dependency in patients with hemorrhage-related hydrocephalus.
      However, the precise mechanism remains unclear.

PMID- 18728571
TI  - Balance deficits after sports-related concussion in individuals reporting
      posttraumatic headache.
AB  - OBJECTIVE: Posttraumatic headache (PTH) may affect neurocognition after sports
      related concussion. To our knowledge, no studies have examined how PTH affects
      balance after concussion using dynamic posturography. The purpose of this study
      is to compare balance after concussion between athletes reporting PTH and
      athletes not reporting PTH. METHODS: We conducted a retrospective, repeated
      measures design with participants grouped by presence of postinjury report of
      headache. Balance testing was conducted on 108 concussed collegiate athletes
      (age, 18.83 +/- 1.27 yr; height, 180.92 +/- 10.01 cm; mass, 83.29 +/- 19.62 kg).
      Presence of PTH during the first postinjury test session (group) and test time
      (baseline, postinjury) served as the independent variables. The composite
      equilibrium score and the somatosensory, vestibular, and visual ratio scores
      served as dependent variables. A 2 x 2 mixed model analysis of variance was used
      to analyze each outcome measure. RESULTS: Significant decreases in all four
      measures assessed were noted after concussion compared with preseason baseline
      measures (P < 0.05). Significant group by test-time interactions were observed,
      suggesting that composite equilibrium (F1106 = 6.6089; P = 0.012) and vestibular
      ratio (F1106 = 7.156; P = 0.009) scores are affected by the presence of PTH.
      Athletes reporting PTH also demonstrated worse visual ratio scores compared with
      individuals not experiencing PTH (F1106 = 4.26; P = 0.041). No other significant
      findings were observed for the somatosensory ratio score. CONCLUSION: Current
      literature proposes that PTH is associated with cognitive deficits. Our study
      indicates that PTH may also contribute to increased balance deficits. We believe
      the deficits may be a result of increased sensory organization challenges after
      injury. Clinicians should be mindful of these findings when managing concussed
      athletes reporting headache.

PMID- 18728572
TI  - Does adherence to treatment targets in children with severe traumatic brain
      injury avoid brain hypoxia? A brain tissue oxygenation study.
AB  - OBJECTIVE: Most physicians rely on conventional treatment targets for
      intracranial pressure, cerebral perfusion pressure, systemic oxygenation, and
      hemoglobin to direct management of traumatic brain injury (TBI) in children. In
      this study, we used brain tissue oxygen tension (PbtO2) monitoring to examine the
      association between PbtO2 values and outcome in pediatric severe TBI and to
      determine the incidence of compromised PbtO2 in patients for whom acceptable
      treatment targets had been achieved. METHODS: In this prospective observational
      study, 26 children with severe TBI and a median postresuscitation Glasgow Coma
      Scale score of 5 were managed with continuous PbtO2 monitoring. The relationships
      between outcome and the 6-hour period of lowest PbtO2 values and the length of
      time that PbtO2 was less than 20, 15, 10, and 5 mmHg were examined. The incidence
      of reduced PbtO2 for each threshold was evaluated where the following targets
      were met: intracranial pressure less than 20 mmHg, cerebral perfusion pressure
      greater than 50 mmHg, arterial oxygen tension greater than 60 mmHg (and
      peripheral oxygen saturation > 90%), and hemoglobin greater than 8 g/dl. RESULTS:
      There was a significant association between poor outcome and the 6-hour period of
      lowest PbtO2 and length of time that PbtO2 was less than 15 and 10 mmHg. Multiple
      logistic regression analysis showed that low PbtO2 had an independent association
      with poor outcome. Despite achieving the management targets described above, 80%
      of patients experienced one or more episodes of compromised PbtO2 (< 20 mmHg),
      and almost one-third experienced episodes of brain hypoxia (PbtO2 < 10 mmHg).
      CONCLUSION: Reduced PbtO2 is associated with poor outcome in pediatric severe
      TBI. In addition, many patients experience episodes of compromised PbtO2 despite
      achieving acceptable treatment targets.

PMID- 18728573
TI  - Effect of microvascular decompression in trigeminal neuralgia patients with or
      without constant pain.
AB  - OBJECTIVE: To study the effect of microvascular decompression (MVD) in trigeminal
      neuralgia (TN) patients with or without constant pain. METHODS: The study
      includes all first-time MVDs for facial pain performed by the senior author (PKE)
      during the 6-year period from 1999 to 2005 in the Department of Neurosurgery at
      the National Hospital. At the time of follow-up, pain relief was assessed using a
      standard mail questionnaire; those patients still having residual pain were
      further examined in the outpatient clinic or interviewed by phone. RESULTS: The
      total study population includes 135 patients who underwent initial MVDs (67% of
      MVDs for TN without constant pain and 33% of MVDs for TN with constant pain). At
      the time of follow-up, the response rate was 95%, which provided us with 128
      patients. The median observation period was 38 months (range, 12-87 mo). For
      episodic pain, MVD caused complete (i.e., 100%) pain relief in 78% of TN patients
      without constant pain and in 77% of TN patients with constant pain before MVD,
      and a significant pain relief (i.e., worst pain marked as 0-3 cm on a 10-cm
      visual analog scale) in 85 and 81%, respectively. For constant pain, MVD caused
      complete pain relief in 70% of the TN patients with constant pain before MVD, and
      significant pain relief in 77%. CONCLUSION: In TN patients with constant pain
      before MVD, significant relief of episodic and constant pain was observed in 81
      and 77%, respectively. Hence, the presence of constant pain should not prevent TN
      patients from being offered MVD.

PMID- 18728574
TI  - Subdural motor cortex stimulation for central and peripheral neuropathic pain: a
      long-term follow-up study in a series of eight patients.
AB  - OBJECTIVE: In certain chronic neuropathic pain (CNP) conditions, extradural
      electrode implantation is preferred to a subdural location for motor cortex
      stimulation (MCS) therapy, but the rationale for this preference remains
      debatable. We provide documented long-term results of subdural MCS in CNP.
      METHODS: Our eight consecutive patients (five men, three women; age range, 45-81
      yr) had either central or peripheral CNP. We localized the central sulcus using
      anatomic landmarks and three-dimensional neuronavigation and by detecting the N20
      wave inversion. We then created an elongated craniotomy (3 cm long x 1 cm wide),
      followed by a linear incision of the dura. An eight-polar plate electrode was
      slipped in subdurally. We used motor-evoked potentials to choose the optimal
      electrode position before fixing the electrode to the dura. RESULTS: Six patients
      had favorable outcomes, and two had poor outcomes at the time of the last
      assessment (mean, 54 mo; range, 19-69 mo). Three patients experienced five
      transient complications, each having an episode of partial motor seizure, one
      that evolved into a secondary generalized seizure. Seizures were related to an
      abrupt increase in stimulation intensity. Two of these three patients also had
      hardware infections that required system replacement, with the electrode
      implanted extradurally at the second implantation in one case because of severe
      arachnoiditis. This change necessitated a greater intensity and a longer duration
      of stimulation to deliver a therapeutic effect equivalent to that with subdural
      MCS. CONCLUSION: In this small series, subdural MCS seemed a tolerable approach
      in the long term for CNP patients. In addition, subdural MCS provided a
      therapeutic effect comparable to that obtained with extradural placement.

PMID- 18728575
TI  - Comparative study of unilateral and bilateral cages with respect to clinical
      outcomes and stability in instrumented posterior lumbar interbody fusion.
AB  - OBJECTIVE: We sought to compare the clinical and radiological results of
      instrumented posterior lumbar interbody fusion (PLIF) using unilateral or
      bilateral polyetheretherketone cages and pedicle screws. METHODS: One hundred
      eighty-seven cases of degenerative spine that had been followed for at least 18
      months were reviewed retrospectively. In 88 cases (147 levels), one cage was
      inserted, and in 99 cases (152 levels), two cages were inserted. Visual analog
      scale, Oswestry disability index, and functional rating indices were measured.
      Lumbar lordosis, lumbar scoliotic and fusion level scoliotic angles, and stable
      fixation were determined before surgery and 12 months postoperatively on standing
      x-rays. Amounts of intra- and postoperative blood loss, total quantities
      transfused, and operation times were also evaluated. RESULTS: No significant
      differences were found between the two groups in terms of visual analog scale,
      Oswestry disability index, functional rating indices, lumbar lordosis, lumbar
      scoliotic angles, fusion level scoliotic angles, or fixation stabilities.
      However, the amounts of postoperative blood loss, total blood loss, and total
      transfusion for two-level PLIF using a unilateral cage were statistically smaller
      than those for two-level PLIF using bilateral cages. Times required for PLIF
      using a unilateral cage were also significantly shorter than those for PLIF using
      bilateral cages. CONCLUSION: Unilateral cage and bilateral pedicle screw
      insertion may be a good alternative surgical option because it provides adequate
      alignment, balance, and mechanical stability in addition to reducing operative
      time, blood loss, and transfusion requirements.

PMID- 18728576
TI  - Prospective randomized comparison of safety and efficacy of nicardipine and
      nitroprusside drip for control of hypertension in the neurosurgical intensive
      care unit.
AB  - OBJECTIVE: The calcium channel blocker nicardipine (NC) is effective for acute
      control of hypertension. However, efficacy and safety in neurosurgical patients
      have not been evaluated. We sought to compare NC with the most commonly used
      agent, sodium nitroprusside (SNP), in patients with subarachnoid or intracerebral
      hemorrhage. METHODS: We performed a prospective randomized comparison of the
      safety and efficacy of NC and SNP in patients with subarachnoid or intracerebral
      hemorrhage. We assessed the number of dose adjustments per patient day,
      proportion of time within set blood pressure parameters, use of additional
      medications for blood pressure control, clinical outcome, and drug-related
      complications. RESULTS: Two hundred patients were screened and 163 patients were
      randomized, including 89 in the SNP group and 74 in the NC group. In 107
      patients, intravenous blood pressure control was started; 60 of these patients
      received SNP and 47 received NC. When analyzed by intent to treat, patients
      randomized to NC had fewer dose adjustments per day: 5.7 versus 8.8 in the
      nitroprusside group (P = 0.0012, Wilcoxon rank-sum test). There were fewer
      additional medications per day to maintain blood pressure control in the NC
      group: 1.4 versus 1.9 for SNP (P = 0.043, Wilcoxon rank-sum test). Blood pressure
      control was similar (NC, 66% of the time within parameters; SNP, 69%). "As
      treated" analysis maintained the apparent advantage of NC. CONCLUSION: When used
      for control of hypertension in patients with subarachnoid or intracerebral
      hemorrhage, NC and SNP were both safe and effective, but patients on an NC drip
      required fewer dose adjustments and fewer additional medications.

PMID- 18728577
TI  - Protective effect of C5a receptor inhibition after murine reperfused stroke.
AB  - OBJECTIVE: The complement cascade has been implicated in cerebral
      ischemia/reperfusion injury. To develop clinically useful therapies that
      successfully manipulate the complement cascade, the individual roles of its
      components must be clearly defined. Previous studies have shown that C5
      inhibition improves outcome after experimental stroke. In this study, we
      investigated the role of C5a in stroke injury by inhibiting its activity at the
      receptor level. METHODS: C5a receptor antagonist or vehicle was administered to
      mice before temporary middle cerebral artery occlusion. Stroke outcomes were
      assessed 24 hours later in all mice using both neurological deficit scores and
      cerebral infarct volumes. RESULTS: Animals treated with C5a receptor antagonist
      experienced significantly decreased infarct volume and demonstrated an improving
      trend in neurological function. CONCLUSION: These findings demonstrate that
      modulation of C5a receptor activity significantly alters the degree of
      neurological damage after experimental reperfused stroke.

PMID- 18728578
TI  - Delayed implantation of intramedullary chitosan channels containing nerve grafts
      promotes extensive axonal regeneration after spinal cord injury.
AB  - OBJECTIVE: We describe a new strategy to promote axonal regeneration after
      subacute or chronic spinal cord injury consisting of intramedullary implantation
      of chitosan guidance channels containing peripheral nerve (PN) grafts. METHODS:
      Chitosan channels filled with PN grafts harvested from green fluorescent protein
      rats were implanted in the cavity 1 week (subacute) or 4 weeks (chronic) after 50
      g clip injury at T8 and were compared with similarly injured animals implanted
      with either unfilled channels or no channels. Functional recovery was measured
      weekly for 12 weeks by open-field locomotion, after which histological
      examination was performed. RESULTS: The implanted channels with PN grafts
      contained a thick tissue bridge containing as many as 35,000 myelinated axons in
      both the subacute and chronic spinal cord injury groups, with the greatest number
      of axons in the channels containing PN grafts implanted subacutely. There were
      numerous green fluorescent protein-positive donor Schwann cells in the tissue
      bridges in all animals with PN grafts. Moreover, these Schwann cells had high
      functional capacity in terms of myelination of the axons in the channels. In
      addition, PN-filled chitosan channels showed excellent biocompatibility with the
      adjacent neural tissue and no obvious signs of degradation and minimal tissue
      reaction at 14 weeks after implantation. In control animals that had unfilled
      chitosan channels implanted, there was minimal axonal regeneration in the
      channels; in control animals without channels, there were large cavities in the
      spinal cords, and the bridges contained only a small number of axons and Schwann
      cells. Despite the large numbers of axons in the chitosan channel-PN graft group,
      there was no significant difference in functional recovery between treatment and
      control groups. CONCLUSION: Intramedullary implantation of chitosan guidance
      channels containing PN grafts in the cavity after subacute spinal cord injury
      resulted in a thicker bridge containing a larger number of myelinated axons
      compared with chitosan channels alone. A chitosan channel containing PN grafts is
      a promising strategy for spinal cord repair.

PMID- 18728580
TI  - Roots of neuroanatomy, neurology, and neurosurgery as found in the Bible and
      Talmud.
AB  - Historical observations and interpretations regarding the treatment of components
      of the nervous system can be found in the writings of the Bible and Talmud. A
      review of topics germane to modern neuroanatomy, neurology, and neurosurgery from
      these early, rich writings is presented herein. These historic writings provide a
      glimpse into the early understanding, description, and treatment of pathologies
      of the nervous system.

PMID- 18728579
TI  - Accuracy of motor axon regeneration across autograft, single-lumen, and
      multichannel poly(lactic-co-glycolic acid) nerve tubes.
AB  - OBJECTIVE: The accuracy of motor axon regeneration becomes an important issue in
      the development of a nerve tube for motor nerve repair. Dispersion of
      regeneration across the nerve tube may lead to misdirection and polyinnervation.
      In this study, we present a series of methods to investigate the accuracy of
      regeneration, which we used to compare regeneration across autografts and single
      lumen poly(lactic-co-glycolic acid) (PLGA) nerve tubes. We also present the
      concept of the multichannel nerve tube that may limit dispersion by separately
      guiding groups of regenerating axons. METHODS: The simultaneous tracing of the
      tibial and peroneal nerves with fast blue and diamidino yellow was performed 8
      weeks after the repair of a 1-cm nerve gap in the rat sciatic nerve to determine
      the percentage of double-projecting motoneurons. Sequential tracing of the
      peroneal nerve with diamidino yellow 1 week before repair and fast blue 8 weeks
      after repair was performed to determine the percentage of correctly directed
      peroneal motoneurons. RESULTS: In the cases in which there was successful
      regeneration across single-lumen nerve tubes, more motoneurons had double
      projections to both the tibial and peroneal nerve branches after single-lumen
      nerve tube repair (21.4%) than after autograft repair (5.9%). After multichannel
      nerve tube repair, this percentage was slightly reduced (16.9%), although not
      significantly. The direction of regeneration was nonspecific after all types of
      repair. CONCLUSION: Retrograde tracing techniques provide new insights into the
      process of regeneration across nerve tubes. The methods and data presented in
      this study can be used as a basis for the development of a nerve tube for motor
      nerve repair.

PMID- 18728581
TI  - Medicosocial problems engendered with the discovery of the Bell-Magendie Law.
AB  - The discovery of the Bell-Magendie Law, which states that the ventral spinal
      roots transmit motor impulses and the posterior roots sensory impulses,
      established a major landmark in the history of neuroscience. It led to further
      elucidation of brain function and served as a starting point for virtually all of
      electrophysiology. During the past two centuries, there has been an intense
      debate as to which of the two scientists deserves the credit for the discovery
      itself and the prominent claim to the discovery. Extensive literature exists in
      this regard, and the goal of the authors is not to dwell on it further but rather
      to summarize the arguments. The major objective of this work, however, is to
      elaborate on the two medicosocial issues that were brought into focus by the
      discovery of the Bell-Magendie Law, namely, the provision of adequate numbers of
      cadavers for the sound anatomic education of medical students, so that the
      despicable practice of "body-snatching" could be abolished, and the prevention of
      cruelty to the experimental animals used for biomedical research. Public opinion
      prevailing at the time of the postulation of the Bell-Magendie Law promoted the
      establishment of the Royal Society for the Prevention of Cruelty to Animals, and
      other similar societies were established worldwide. The authors summarize the
      current status of these two issues.

PMID- 18728584
TI  - Microsurgical and endoscopic anatomy of Liliequist's membrane: a complex and
      variable structure of the basal cisterns.
AB  - OBJECTIVE: Descriptions of Liliequist's membrane, as reported in the literature,
      vary considerably. In our cadaveric study of Liliequist's membrane, we attempted
      to clarify and define its anatomic features and boundaries, as well as its
      relationship with surrounding neurovascular structures. We describe the
      embryology of this membrane as a remnant of the primary tentorium. The clinical
      significance of our findings is discussed with respect to third ventriculostomy
      and surgical approaches to basilar tip aneurysms, suprasellar arachnoid cysts,
      and perimesencephalic hemorrhage. METHODS: Thirteen formalin-fixed adult
      cadaveric heads were injected with colored silicone. After endoscopic exploration
      of Liliequist's membrane, a bilateral frontal craniotomy was performed, and the
      frontal lobes were removed to fully expose Liliequist's membrane. RESULTS:
      Liliequist's membrane is a complex and highly variable structure that is composed
      of either a single membrane or two leaves. The membrane was absent in two
      specimens without any clear demarcation between the interpeduncular, prepontine,
      and chiasmatic cisterns. CONCLUSION: Understanding the variable anatomy of
      Liliequist's membrane is important, particularly to improve current and
      forthcoming microsurgical and endoscopic neurosurgical procedures. It is
      important as a surgical landmark in various neurosurgical operations and in the
      physiopathology of several pathological processes (suprasellar arachnoid cysts
      and perimesencephalic hemorrhage).

PMID- 18728585
TI  - The accessory middle cerebral artery: anatomic report.
AB  - OBJECTIVE: An accessory middle cerebral artery (MCA) usually originates between
      the A1 and proximal A2 segment of the anterior cerebral artery, reaches the
      sylvian fissure, and supplies the territory of the MCA. This anomaly has been
      associated with cerebral aneurysms and Moyamoya disease. We report an accessory
      MCA arising from the A2 segment. METHODS: A cadaveric head, fixed in formalin
      solution and injected with red and blue silicone on its vascular tree to trace
      intracranial and extracranial vessels, was dissected. RESULTS: An accessory MCA
      was found arising from the A2 segment of the anterior cerebral artery and feeding
      the basal and inferior surface of the inferior frontal gyrus. In our specimen,
      the vessel was associated with intracranial aneurysms at other locations.
      CONCLUSION: Although anomalies of the MCA are rare, neurosurgeons must be
      familiar with such anatomic variations. An accessory MCA can be associated with
      Moyamoya disease and aneurysms at its junction with the anterior cerebral artery.
      Patients with this anomaly may, therefore, have an increased risk for developing
      aneurysms and other neurovascular complications. By obstructing the surgical
      view, an accessory MCA may increase the difficulty of exposing lesions in the
      vicinity of the optic chiasm.

PMID- 18728586
TI  - Dorsal lumbar interbody fusion for chronic axial, mechanical low back pain: a
      modification of two established techniques.
AB  - Lumbar spinal fusion is a popular method for treating degenerative disc disease
      leading to chronic low back pain. Some of the techniques most commonly undertaken
      are posterior lumbar interbody fusion and transforaminal lumbar interbody fusion.
      These techniques have their own advantages and disadvantages. In this article, we
      briefly describe a modified technique, dorsal lumbar interbody fusion, which
      retains the advantages and avoids the disadvantages of the others. The goal of
      this procedure is to combine the aggressive decompression of both the thecal sac
      and bilateral nerve roots and symmetrical bilateral graft placement obtained via
      the posterior lumbar interbody fusion with the transforaminal placement of
      interbody grafts obtained via the transforaminal lumbar interbody fusion
      procedure. This modification has several advantages: it permits more aggressive
      removal of the disc bilaterally, larger and more symmetrical lordotic-shaped
      carbon fiber cages and structural allograft can be placed bilaterally, and the
      nerve roots can be aggressively decompressed bilaterally.

PMID- 18728587
TI  - A new ceramic interspinous process spacer for lumbar spinal canal stenosis.
AB  - OBJECTIVE: Because surgery in elderly patients should be minimally invasive,
      interspinous process distraction has been widely used in this group to treat
      lumbar canal stenosis. We developed a new interspinous process distraction spacer
      composed of hydroxyapatite ceramic. In this work, we demonstrate the usefulness
      of this novel device. METHODS: Since 2003, we operated on 19 elderly patients
      with lumbar canal stenosis, including 14 men and five women. Their mean age was
      70.1 years. We compared the intervertebral angle, posterior disc height, and
      interspinous process distance on midsagittal magnetic resonance images obtained
      before and after the surgery. We also assessed clinical outcomes by using the
      Visual Analog Scale and the Zurich Claudication Questionnaire. RESULTS: The
      average operation time per level was 44.7 minutes. Postoperatively, there were
      significant changes in the angle (from 12.5 to 8.6 degrees, P < 0.0001), the
      posterior disc height (from 10.6 to 13.1 mm, P < 0.0001), and the interspinous
      process distance (from 9.7 to 14.1 mm, P < 0.0001). The clinical outcomes, which
      we assessed by using the Visual Analog Scale and the Zurich Claudication
      Questionnaire, were considered satisfactory. (Visual Analog Scale, from 6.88 to
      3.00; Zurich Claudication Questionnaire, symptom severity domain from 2.94 to
      1.92, physical function from 2.51 to 1.73.) CONCLUSION: Our ceramic spacer is
      useful in the treatment of elderly patients with lumbar canal stenosis. Treatment
      comprises an easy surgical procedure and produces no metal artifact on
      radiological evaluations, such as magnetic resonance imaging and computed
      tomographic scans.

PMID- 18728588
TI  - En bloc total sacrectomy performed in a single stage through a posterior
      approach.
AB  - OBJECTIVE: Total sacrectomies are performed for extensive en bloc tumor
      resections. Exposure traditionally combines a posterior approach with a
      laparotomy to facilitate vascular control. We present a case of a total en bloc
      sacrectomy performed entirely through the posterior approach, thereby avoiding
      the need for a laparotomy. CLINICAL PRESENTATION: A 57-year-old man presented
      with sacral pain and loss of bowel and bladder function. A large sacral mass was
      identified and submitted to biopsy. Results were consistent with an
      osteoblastoma, although osteosarcoma could not be excluded on pathological
      examination. The patient was taken to the operating room for a total sacrectomy
      and en bloc resection of the mass. TECHNIQUE: Lateral iliac osteotomies were
      performed, followed by an L5-S1 discectomy and resection of the annulus, thus
      mobilizing the sacrum. Gradual distraction of the interspace coupled with upward
      traction of the sacrum provided an anterior exposure through which the internal
      iliac vessels were controlled, dissected, and divided. A combined transperineal
      approach completed the posterior dissection and the tumor was delivered en bloc.
      Lumbopelvic reconstruction was performed simultaneously. CONCLUSION: With the use
      of interspace distraction and sacral elevation to facilitate vascular control, a
      total sacrectomy was performed without the need for the anterior exposure of a
      laparotomy.

PMID- 18728589
TI  - Magnetically guided neuronavigation of flexible instruments in shunt placement,
      transsphenoidal procedures, and craniotomies.
AB  - OBJECTIVE: Magnetically guided neuronavigation of flexible instruments is a new
      tool that can be used in the frameless navigation of deep-seated lesions or shunt
      placements. Disadvantages of optical systems such as the line-of-sight problem,
      the necessity of rigid pin fixation of the head, and missing tracking of the tip
      of flexible instruments should be solved by the new tracking system. Until now,
      the accuracy of magnetically guided systems was mostly estimated in laboratory
      setups. METHODS: In this study, intraoperative accuracy of the system was tested
      in 60 patients with either hydrocephalus or cranial base tumors. In daily routine
      use, different operative setups with a variety of metallic instruments were
      examined. Accuracy of the neuronavigation system was estimated, comparing
      microscopically or endoscopically identified anatomic landmarks with
      neuronavigated data and postoperative computed tomographic scans. RESULTS: The
      main advantage of the new system is the tracking of a magnetic coil at the tip of
      a flexible instrument. After an initial learning curve during the developmental
      phase of the system, the latter showed reliable accuracy values with no operative
      setups leading to mismatch of more than 2 mm. CONCLUSION: Tracking of flexible
      instruments was easily accomplished as the tip of the instrument was followed
      within the patient's head. There were no major interferences with other metallic
      instruments within the surgical field.

PMID- 18728590
TI  - Anatomoradiological landmarks for accuracy of radiofrequency thermorhizotomy in
      the treatment of trigeminal neuralgia.
AB  - OBJECTIVE: The correct positioning of the electrode is of prime importance for
      effectiveness and selectivity of percutaneous trigeminal radiofrequency
      thermorhizotomy (RF-TR) for the treatment of trigeminal neuralgia (TN). The aim
      of our study was to establish some anatomoradiological landmarks for the purpose
      of accurate placement of the electrode tip in RF-TR. METHODS: Of 1000 patients
      who underwent RF-TR, 100 were retrospective and randomly selected and divided
      into study groups according to postoperative hypoesthesia in the trigeminal nerve
      divisions. The patients' petroclival angle, petroelectrodal angle, electrode tip,
      and the petroelectrodal angle/petroclival angle ratio were calculated on lateral
      cranial x-rays. These measurements were then correlated with the topography of
      hypoesthesia obtained by the RF-TR to define the anatomoradiological x-ray
      landmarks corresponding to the divisions of the trigeminal root. The
      postoperative hypoesthesia groups were correlated with their respective
      preoperative pain topography to check the accuracy of the thermolesion. In
      addition, the intraoperatively evoked paresthesia responses and the side effects
      were evaluated. The results were analyzed using a paired-samples Student's t
      test, the chi test, and one-way analysis of variance, followed by Bonferroni and
      Tamhane post hoc tests. RESULTS: All study groups were comparable with respect to
      age, sex, side effects, electrode tip location, side of TN, and values of
      petroclival angle. The lowest values of petroelectrodal angle/orbitomeatal
      electrodal angle and petroelectrodal angle/ petroclival angle were detected in
      patients with V3 TN, whereas the greatest values were in patients who had TN in
      all branches of the trigeminal nerve. The greatest height of the electrode was in
      patients who had TN in all branches, whereas the least height was in patients
      with V3 TN. When the results were compared with each other, the mean differences
      were found to be statistically significant between V3 TN patients and the other
      groups with different P values. There was no statistical difference between the
      postoperative hypoesthesia data and the preoperative pain topography, which
      demonstrated evidence of the accuracy of the thermolesion in our series.
      CONCLUSION: Our data suggest that the determination of the presented landmarks
      allows customization to individual patient anatomy and may help the surgeon
      achieve a more selective effect with a variety of percutaneous procedures for
      each branch of the trigeminal root.

PMID- 18728591
TI  - Three-dimensional visualization of neurovascular compression: presurgical use of
      virtual endoscopy created from magnetic resonance imaging.
AB  - OBJECTIVE: To assess the usefulness of presurgical simulation of microvascular
      decompression (MVD) by virtual endoscopy (VE), a new tool to analyze three
      dimensionally reconstructed magnetic resonance data sets in patients with
      trigeminal neuralgia or hemifacial spasm (HFS). METHODS: In 17 patients (10 with
      trigeminal neuralgia and seven with HFS) determined to be candidates for MVD, we
      performed presurgical simulation of MVD using VE. We used constructive
      interference in steady-state imaging and magnetic resonance angiography to obtain
      the original images. VE findings were compared with surgical findings. RESULTS:
      The three-dimensional relations between visible structures seen on VE were
      consistent with intraoperative findings in all patients. In total, 20 (91%) of 22
      neurovascular compression sites in all 17 patients were correctly delineated on
      VE, with the exception of two small branches identified as offending vessel in
      two patients with HFS. Perforators that were not apparent on VE limited our
      ability to accomplish transpositioning of the offending vessels as simulated. The
      positions of structures that can affect individual surgical approaches, such as
      the petrosal vein, cerebellar flocculus, and vertebral artery, were also
      adequately predicted on VE. All patients had excellent surgical outcomes.
      CONCLUSION: Presurgical VE in patients with trigeminal neuralgia or HFS is a
      novel technique that provides excellent visualization of the three-dimensional
      relations between neurovascular structures and allows simulation of MVD.

PMID- 18728592
TI  - Computed tomography-guided percutaneous trigeminal tractotomy-nucleotomy.
AB  - OBJECTIVE: The destruction of the descending trigeminal tractus in the medulla is
      known as trigeminal tractotomy (TR), whereas the lesioning of the nucleus
      caudalis is known as trigeminal nucleotomy (NC). Trigeminal TR and/or NC
      procedures can be used in a large group of pain syndromes, such as
      glossopharyngeal, vagal, and geniculate neuralgias, atypical facial pain,
      craniofacial cancer pain, postherpetic neuralgias, and atypical forms of
      trigeminal neuralgia. METHODS: In this study, anatomic and technical details of
      the procedure and the experience gained from 65 patients over the course of 20
      years are discussed. Patients' pain scores and Karnofsky Performance Scale scores
      were evaluated pre- and postoperatively (postoperative Day 1). RESULTS: The best
      results were obtained in the second-largest group (vagoglossopharyngeal
      neuralgia, n = 17) and in geniculate neuralgia (n = 4). Patients with atypical
      facial pain (n = 21; 13 women, eight men) accounted for the largest group to
      undergo computed tomography-guided TR-NC surgery; pain relief was achieved in 19
      of these patients. In the third-largest group (craniofacial and oral cancer pain,
      n = 13), 11 of 13 patients were successfully treated with TR-NC. Four of five
      patients with failed trigeminal neuralgia were also effectively treated with TR
      NC. CONCLUSION: We propose that computed tomography-guided TR-NC provides direct
      visualization of the target-electrode relation and can be considered a first-step
      procedure in patient management. In view of its high efficacy, low complication
      rate, and minimal invasiveness, computed tomography-guided trigeminal TR-NC is a
      safe and effective procedure in the treatment of intractable facial pain
      syndromes.

PMID- 18728593
TI  - Computed tomographic evaluation of anatomic relationship between the paranasal
      structures and orbital contents for endoscopic endonasal transethmoidal approach
      to the orbit.
AB  - OBJECTIVE: Some recent reports have described the endoscopic endonasal removal of
      orbital tumors. However, the surgical anatomy for an endoscopic endonasal
      approach has not yet been clearly described. The first aim of this study is to
      examine the anatomic relationship between the paranasal and orbital structures
      with the use of computed tomographic imaging and to find useful landmarks for a
      transethmoidal approach to the orbital retrobulbar space. The second aim is to
      determine a procedure to minimize the possibility of bleeding via the endonasal
      transethmoidal approach. METHODS: One hundred axial and coronal computed
      tomographic scans obtained between January 2004 and December 2005 were evaluated.
      RESULTS: The third lamella was located posteriorly to the posterior end of the
      eyeball on all axial computed tomographic scans, thus indicating that it may be a
      useful landmark for the localization of the retrobulbar space. There was a large
      variation in the relationship among the inferior and medial rectus muscles and
      the ethmoid-maxillary plate regarding their location. These results demonstrate
      that the route into the orbit via the ethmoid-maxillary plate gains no access to
      the medial side of the medial rectus muscle, the region with abundant blood
      vessels. CONCLUSION: These results suggest that the third lamella and ethmoid
      maxillary plate are the most important anatomic landmarks for an endoscopic
      endonasal transethmoidal approach to the orbital retrobulbar space.

PMID- 18728594
TI  - Trephine epilepsy surgery: the inferior temporal gyrus approach.
AB  - OBJECTIVE: To describe our technique for temporal lobe epilepsy surgery using a
      minimal-access approach. METHODS: Our epilepsy surgery registry was reviewed, and
      all patients with at least 2 years follow-up were queried. Clinical data included
      age, sex, side of lesion, presence of mesial temporal sclerosis, surgical
      complications, and Engel class outcome. Our operation was performed through a 6-
      to 8-cm linear vertical incision extending upward from just anterior to the
      tragus. An oval trephine (2 x 3 cm) craniotomy was performed flush with the
      middle fossa floor. Resection of part of the inferior temporal gyrus provided a
      corridor to the mesial temporal lobe. Identification of the temporal horn of the
      lateral ventricle was followed by resection of the parahippocampal gyrus, the
      amygdala, and the uncus. Segregation of the hippocampus and its subsequent
      resection in subpial fashion preserved perimesencephalic vasculature. Use of a
      fine suture for skin closure produced a cosmetic result. RESULTS: In our 8-year
      series of 201 patients with a minimum follow-up duration of 2 years, we have
      observed a low number (1.5%) of complications and a 78% rate of Engel Class I
      seizure-free outcome. Surgery times were short (average, 2-5 h; range, 2 h 20 min
      4 h 10 min) and hospital stays brief (<3 d; range, 1-4 d). CONCLUSION: Our
      results suggest that the trephine craniotomy with the inferior temporal gyrus
      approach has the advantage of minimal invasiveness, including brief operative
      times and postoperative stays, and also effectively reduces or eradicates
      medically intractable seizures.

PMID- 18728595
TI  - Safety and accuracy of bedside external ventricular drain placement.
AB  - OBJECTIVE: To study the safety and accuracy of ventriculostomy by neurosurgical
      trainees. METHODS: Initial computed tomographic studies of 346 consecutive
      patients who underwent bedside ventriculostomy were reviewed retrospectively.
      Diagnosis, catheter tip location, midline shift, and procedural complications
      were tabulated. To analyze catheter placement, we used a new grading system:
      Grade 1, optimal placement in the ipsilateral frontal horn or third ventricle;
      Grade 2, functional placement in the contralateral lateral ventricle or
      noneloquent cortex; and Grade 3, suboptimal placement in the eloquent cortex or
      nontarget cerebrospinal fluid space, with or without functional drainage.
      Statistical analysis was performed using Fisher's exact test and a weighted kappa
      coefficient. RESULTS: Diagnoses included the following: subarachnoid hemorrhage,
      n = 153 (44%); trauma, n = 64 (18%); intracerebral hemorrhage/intraventricular
      hemorrhage, n = 63 (18%); and other, n = 66 (20%). There were 266 (77%) Grade 1,
      34 (10%) Grade 2, and 46 (13%) Grade 3 catheter placements. Hemorrhagic
      complications occurred in 17 (5%). Four patients (1.2%) were symptomatic, with
      two (0.6%) requiring surgery. Inter- and intraobserver agreement was almost
      perfect (kappa = 0.846 and 0.922, respectively) as applied to our grading system.
      Rates of suboptimal placement were highest in patients with midline shift (P =
      0.059) and trauma (P = 0.0001). Rates of optimal placement were highest in
      patients with subarachnoid hemorrhage (P = 0.003) and when the catheter was
      placed ipsilateral to the side of midline shift (P = 0.063). Neither the
      resident's training experience nor the side of placement seemed to affect
      accuracy. CONCLUSION: Bedside ventriculostomy is a safe and accurate procedure
      for intracranial pressure monitoring and cerebrospinal fluid drainage.

PMID- 18728596
TI  - Complications of endoscopic third ventriculostomy in previously shunted patients.
AB  - OBJECTIVE: Endoscopic third ventriculostomy (ETV) is considered to be a safe and
      effective treatment in selected patients as an initial treatment for obstructive
      hydrocephalus and at the time of shunt malfunction in previously shunted
      patients. We compared the outcome and complications of ETV between patients with
      newly diagnosed hydrocephalus and those with previous shunting procedures.
      METHODS: A retrospective review of patients undergoing ETV from 1996 to 2004 at
      Alberta's Childrens Hospital and Foothills Medical Centre was completed. Patient
      data included symptoms at clinical presentation, cause of hydrocephalus, age at
      initial shunt, number of previous shunt revisions, age at ETV, complications, and
      subsequent shunting procedures performed. RESULTS: A total of 131 patients were
      identified with a minimum follow-up duration of 1 year; 71 (82.5%) of 86 patients
      who underwent ETV as a primary procedure and 36 (80%) of 45 patients who had ETV
      at the time of shunt malfunction were shunt-free at the last follow-up
      evaluation. Patients younger than 1 year old who underwent ETV were more likely
      to require an additional procedure for control of their hydrocephalus (P < 0.01).
      Serious complications after ETV occurred more frequently in patients who
      presented at the time of shunt malfunction (14 of 45 patients, 31%) compared with
      patients who underwent primary ETV (seven of 86 patients, 8%) (P = 0.02).
      Previously shunted patients with a history of two or more revisions (P = 0.03)
      and who experienced a serious complication at the time of ETV (P = 0.01) were
      more likely to require shunt replacement. CONCLUSION: ETV is an effective
      treatment both in selected patients with newly diagnosed hydrocephalus and in
      patients with a previous shunting procedure who are presenting with malfunction.
      Complications of ETV occur more frequently in previously shunted patients than in
      patients treated for newly diagnosed hydrocephalus, and care must be taken in the
      selection and treatment of these patients.

PMID- 18728597
TI  - Collagen matrix in decompressive hemicraniectomy.
AB  - OBJECTIVE: Decompressive hemicraniectomy is an accepted treatment for otherwise
      untreatable intracranial hypertension. The aim of this prospective randomized
      study is to evaluate the benefit of application of collagen matrix as an onlay
      graft to reduce operating time during hemicraniectomy and to facilitate dural
      dissection during second-stage cranioplasty. METHODS: Thirty-four consecutive
      patients were randomized to receive collagen matrix during hemicraniectomy or to
      undergo the conventional procedure. Specific time points were recorded during
      hemicraniectomy and cranioplasty. Intra- and postoperative complications, time
      course of Glasgow Coma Scale, Barthel's, and Early Rehabilitation Indices were
      monitored. The surgeon had to rate the convenience of the procedure if collagen
      matrix was used. Cost implications are discussed. RESULTS: The use of collagen
      matrix during hemicraniectomy resulted in a reduction of combined operating time
      for hemicraniectomy and cranioplasty by an average of 19.7%. The rate of
      cerebrospinal fluid effusion during cranioplasty was 13% when collagen was used
      and 58% in the control group. None of the patients who received collagen
      developed cerebrospinal fluid effusion persisting longer than 1 week, compared
      with 33% of patients in the control group. A total of 85% of the surgeons rated
      the use of collagen matrix as being easier than usual; the rest did not see a
      difference. CONCLUSION: The use of collagen matrix to cover the dural defect
      during hemicraniectomy reduces operating time in hemicraniectomy and
      cranioplasty. The complication rate (cerebrospinal fluid effusion), total
      treatment time, and time on intensive care unit can be reduced, giving a
      potential for cost reduction. There was no difference in the rehabilitative
      outcome.

PMID- 18728598
TI  - Polyethylene glycol hydrogel dural sealant may reduce incisional cerebrospinal
      fluid leak after posterior fossa surgery.
AB  - OBJECTIVE: Incisional cerebrospinal fluid (CSF) leak remains a significant cause
      of morbidity, particularly after posterior fossa surgery, with ranges between 4
      and 17% in most series. We aimed to determine whether the use of a new
      polyethylene glycol (PEG) dural sealant product (DuraSeal; Confluent Surgical,
      Waltham, MA) is effective at preventing incisional CSF leak after posterior fossa
      surgery. METHODS: One hundred cases of posterior fossa surgery with the PEG dural
      sealant applied at the time of dural closure were prospectively observed from May
      2005 to April 2006. All patients underwent posterior fossa craniotomy or
      craniectomy. Clinical histories were followed to document cases of incisional CSF
      leak, pseudomeningocele, meningitis, wound infection, and interventions required
      to treat a CSF leak or pseudomeningocele. A retrospective cohort of 100 patients
      treated in a similar fashion but with fibrin glue augmented dural closure served
      as controls. RESULTS: In the PEG group, two of 100 (2%) patients developed an
      incisional CSF leak postoperatively. By comparison, 10 of 100 (10%) patients in
      whom fibrin glue was used developed an incisional CSF leak. This difference was
      statistically significant, with a P value of 0.03. There were no significant
      differences in the rates of pseudomeningocele, meningitis, or other postoperative
      interventions. CONCLUSION: The application of PEG dural sealant to the closed
      dural edges may be effective at reducing incisional CSF leak after posterior
      fossa surgery.

PMID- 18728599
TI  - Newly designed ergonomic surgical binocular telescope with angulated optic axis.
AB  - OBJECTIVE: Magnification by surgical loupes has the distinct merits of agility
      and nimbleness in observation, a wide stereo base effectuating superior depth
      sensation, and light augmentation by an objective lens that is larger than the
      pupil. However, continuous use of these loupes causes neck strain for surgeons as
      a result of flexion posture and fatigue. To minimize the strain and fatigue and
      maximize the advantages and performance of binocular telescopes, we have
      developed a novel optical design. METHODS: To allow observation of the operative
      field with the surgeon's neck and eye in a straight position, the light path of
      the telescopes was angulated downward with roof prisms. For maximum image
      quality, Keplerian real-image optics were adopted. RESULTS: The optics, finishing
      of the lens, and assembly were perfected through practical trials of more than
      500 procedures over a period of 3 years. CONCLUSION: The new ergonomically
      designed optics provide excellent image quality comparable to standing
      microscopes in the low to medium range of magnification, while effectively
      reducing the neck flexion of surgeons working in the operative field below and
      relieving the surgeon's fatigue during hours of continuous use.

PMID- 18728600
TI  - Real-time magnetic resonance-guided laser thermal therapy for focal metastatic
      brain tumors.
AB  - OBJECTIVE: We report the initial results of a pilot clinical trial exploring the
      safety and feasibility of the first real-time magnetic resonance-guided laser
      induced thermal therapy of treatment-resistant focal metastatic intracranial
      tumors. METHODS: Patients with resistant metastatic intracranial tumors who had
      previously undergone chemotherapy, whole-brain radiation therapy, and
      radiosurgery and who were recused from surgery were eligible for this trial.
      Under local anesthesia, a Leksell stereotactic head frame was used to insert a
      water-cooled interstitial fiberoptic laser applicator inside the cranium. In the
      bore of a magnetic resonance imaging (MRI) scanner, laser energy was delivered to
      heat the tumor while continuous MRI was performed. A computer workstation
      extracted temperature-sensitive information to display images of laser heating
      and computed estimates of the thermal damage zone. Posttreatment MRI scans were
      used to confirm the zone of thermal necrosis, and follow-up was performed at 7,
      15, 30, and 90 days after treatment. RESULTS: In all cases, the procedure was
      well tolerated without secondary effect, and patients were discharged to home
      within 14 hours after the procedure. Follow-up imaging showed an acute increase
      in apparent lesion volume followed by a gradual and steady decrease. No tumor
      recurrence within thermal ablation zones was noted. CONCLUSION: In this ongoing
      trial, a total of four patients have had six metastatic tumors treated with laser
      thermal ablations. Magnetic resonance-guided laser-induced thermal therapy
      appears to provide a new, efficient treatment for recurrent focal metastatic
      brain disease. This therapy is a prelude to the future development of closed-head
      interventional MRI techniques in neurosurgery.

PMID- 18728601
TI  - Combined transventricular and supracerebellar infratentorial approach preserving
      the vermis in giant pediatric posterior fossa midline tumors.
AB  - OBJECTIVE: Giant pediatric midline tumors of the posterior fossa involving the
      fourth ventricle and the tectal region are difficult to approach and present a
      high risk of postoperative neurological deficits. Children with sequelae such as
      cerebellar mutism and ataxia experience a compromise in their quality of life.
      Here, we present our combined transventricular and supracerebellar infratentorial
      approach to avoid complications of vermian splitting. METHODS: The combined
      transventricular and supracerebellar infratentorial approach described here was
      used in a total of four pediatric patients. A medial suboccipital craniotomy with
      opening of the foramen magnum and resection of the C1 lamina was performed with
      the patient in the semisitting position. The tumor mass filling the fourth
      ventricle was removed via a transventricular telovelar route through the foramen
      of Magendie, preserving the vermis. The rostral tumor portions in the peritectal
      region extruding up to the thalami were exposed and resected via an
      infratentorial supracerebellar route to preserve the venous drainage of the
      cerebellum. RESULTS: There were no new neurological deficits postoperatively. Two
      patients had low-grade astrocytomas, and two patients had malignant tumors.
      Complete tumor resection was achieved in two patients, and near-total tumor
      removal in the two others. CONCLUSION: The combined transventricular and
      supracerebellar infratentorial approach offers a unique possibility of safely
      removing giant pediatric midline tumors. Splitting of the cerebellar vermis is
      not necessary for removal of such tumors.

PMID- 18728602
TI  - Fat implant is superior to muscle implant in vestibular schwannoma surgery for
      the prevention of cerebrospinal fluid fistulae.
AB  - OBJECTIVE: Meticulous sealing of opened air cells in the petrous bone is
      necessary for the prevention of cerebrospinal fluid (CSF) fistulae after
      vestibular schwannoma surgery. We performed a retrospective analysis to determine
      whether muscle or fat tissue is superior for this purpose. METHODS: Between
      January 2001 and December 2006, 420 patients underwent retrosigmoidal
      microsurgical removal by a standardized procedure. The opened air cells at the
      inner auditory canal and the mastoid bone were sealed with muscle in 283 patients
      and with fat tissue in 137 patients. Analysis was performed regarding the
      incidence of postoperative CSF fistulae and correlation with the patient's sex
      and tumor grade. RESULTS: The rate of postoperative CSF leak after application of
      fat tissue was lower (2.2%) than after use of muscle (5.7%). Women had less
      postoperative CSF leakage (3.4%) than men (5.6%). There was an inverse
      correlation with tumor grade. Patients with smaller tumors seemed to have a
      higher rate of CSF leakage than those with large tumors without hydrocephalus.
      Only large tumors with severe dislocation of the brainstem causing hydrocephalus
      showed a higher incidence of CSF leaks. CONCLUSION: Fat implantation is superior
      to muscle implantation for the prevention of CSF leakage after vestibular
      schwannoma surgery and should, therefore, be used for the sealing of opened air
      cells in cranial base surgery.

PMID- 18728603
TI  - Endoscopic reconstruction of the cranial base using a pedicled nasoseptal flap.
AB  - OBJECTIVE: Reconstruction of the cranial base using vascularized tissue promotes
      rapid and complete healing, thus avoiding complications caused by persistent
      communication between the cranial cavity and the sinonasal tract. The Hadad
      Bassagasteguy flap (HBF), a neurovascular pedicled flap of the nasal septum
      mucoperiosteum and mucoperichondrium based on the nasoseptal artery, seems to be
      advantageous for the reconstruction of the cranial base after endonasal cranial
      base surgery. METHODS: We performed a retrospective review of patients who
      underwent endonasal cranial base surgery at the University of Pittsburgh Medical
      Center from January 30, 2006 to January 30, 2007, identifying patients who
      experienced reconstruction with a vascularized septal mucosal flap (HBF). We
      analyzed the demographic data, pathological characteristics, site and extent of
      resection, use of cerebrospinal fluid (CSF) diversion techniques, and outcome.
      RESULTS: Seventy-five patients who underwent endonasal cranial base endoscopic
      surgery received repair with the HBF. In this population, we encountered eight
      postoperative CSF leaks (10.66%), all in patients who required intra-arachnoidal
      dissection. When we correct the statistical analysis to include only patients
      with intra- arachnoidal lesions, the postoperative CSF leak rate is 14.5% (eight
      of 55 patients). It is notable that six CSF (33%) leaks occurred in our first 25
      repairs, whereas we encountered only two postoperative leaks (4%) in the last 50
      patients. The corrected CSF leak rate, considering only intra-arachnoidal
      lesions, was two (5.4%) of 37 patients. This improvement in the CSF leak rate
      reflects our growing experience and comfort with this reconstructive technique.
      All of our failures could be matched to a specific technical mistake. In
      addition, we modified the flap-harvesting technique to allow for staged
      procedures and the removal of caudal lesions. These special circumstances require
      storage of the flap in the antrum during the removal of caudal lesions, and
      suturing of the flap in its original position for staged procedures. One patient
      experienced a posterior nose bleed from the posterior nasal artery. This was
      controlled with bipolar electrocautery, thereby preserving the flap blood supply.
      We encountered no infectious or wound complications in this series of patients.
      The donor site accumulates crusting, which requires debridement until
      mucosalization is complete; this usually occurs 6 to 12 weeks after surgery.
      CONCLUSION: The HBF is a versatile and reliable reconstructive technique for
      repairing defects of the anterior, middle, clival, and parasellar cranial base.
      Its use has resulted in a significant decrease in our incidence of CSF leaks
      after endonasal cranial base surgery. Attention to technical details is of
      paramount importance to achieve the best outcomes.

PMID- 18728604
TI  - Internal carotid artery aneurysms occurring at the origin of fetal variant
      posterior cerebral arteries: surgical and endovascular experience.
AB  - OBJECTIVE: A fetal variant posterior cerebral artery (fetal PCA) is an
      embryological remnant in which the PCA is primarily supplied via the anterior
      cerebral circulation. Internal carotid artery (ICA) aneurysms originating from
      the takeoff of fetal PCA vessels deserve special attention before surgical or
      endovascular obliteration because of a greater potential for ischemic injury. We
      present the first series of ICA-posterior communicating artery (PComA) aneurysms
      originating at the takeoff of fetal PCA vessels that were treated by surgical or
      endovascular intervention. METHODS: A retrospective chart review was conducted
      for all patients who underwent surgical and endovascular treatment of an ICA
      PComA aneurysm at Los Angeles County-University of Southern California Medical
      Center during a 15-year period (1991-2006) to identify cases with aneurysms
      originating from fetal variant PCAs. Data were retrospectively reviewed and
      analyzed. RESULTS: During a 15-year period, 271 patients were treated for 273 ICA
      PComA aneurysms. Aneurysms occurring at the origin of fetal PCAs were identified
      in 30 patients (11%). There were 23 women (77%) and seven men (23%) (sex
      difference, P = 0.0035). Twenty-four patients underwent surgical clipping,
      whereas six patients underwent endovascular coiling. The mean aneurysm size was 7
      mm. The mean ischemia time with temporary clipping (12 cases) was 4.5 minutes.
      Intraoperative rupture occurred in four surgical cases (17%). Postoperative
      angiography demonstrated occlusion of the fetal PCA in one case after clip
      ligation (3%), with an ensuing occipital infarct yet no clinical symptoms.
      CONCLUSION: ICA-PComA aneurysms originating from fetal PCA vessels may pose a
      more substantial risk for infarction and subsequent neurological sequelae with
      surgical or endovascular obliteration. Fetal variant circulations were identified
      at the PComA origin in 11% of ICA-PComA aneurysm patients and were more commonly
      encountered in women. The decision of surgical versus endovascular treatment of
      fetal PCA aneurysms must be carefully considered, given the greater potential for
      ischemic injury with parent vessel occlusion.

PMID- 18728605
TI  - Thalamic and basal ganglia arteriovenous malformations: redefining "inoperable".
AB  - Deep arteriovenous malformations of the basal ganglia and thalamus have an
      aggressive natural history and present a therapeutic challenge. More often than
      not, these lesions are deemed "inoperable" and are treated expectantly or with
      stereotactic radiosurgery. In some cases, clinical details combined with an
      opportune route of access dictate surgical resection. History of hemorrhage,
      small lesion size, and deep venous drainage each add to the aggressive natural
      history of these malformations. Interestingly, these same factors can point
      toward surgery. We present a discussion of the microsurgical techniques involved
      in managing these lesions, with an emphasis on situations that allow these
      lesions to be approached surgically.

PMID- 18728606
TI  - Transanterior perforating substance approach to the thalamomesencephalic
      junction.
AB  - OBJECTIVE: Lesions in the thalamomesencephalic junction can be reached via an
      anterolateral approach, interhemispheric approach, transcortical (parieto
      occipital lobule) approach, subtemporal approach, supracerebellar approaches, or
      transsylvian-insular approach. We now describe a new approach, a transanterior
      perforating substance approach, to this territory. METHODS: A 33-year-old man
      with progressive right arm tremors, mild hemiparesis, and a cavernous
      malformation of the thalamomesencephalic junction was followed for 5 years.
      Because of clinical progression, he underwent a left orbitozygomatic approach to
      the cavernous malformation, which could not be accessed because of a high-riding
      basilar artery. Hence, a new transsylvian corridor of exposure was developed
      using frameless neuronavigation. The trajectory, which was dorsal to M1, led
      through the perforating branches of M1. Care was taken to avoid violating any
      arterial perforators. To reach the lesion, a small opening into the brain was
      created near the optic tract. RESULTS: The cavernous malformation was resected
      totally. Postoperatively, the patient's tremors were cured. No visual deficits
      were encountered. Imaging showed a small ischemic stroke in the basal ganglia
      likely related to manipulation of a perforator. Initially, his hemiparesis
      worsened, but it improved significantly within 10 months with only a moderate
      decrease in strength. CONCLUSION: The transanterior perforating substance
      approach effectively allowed access to the thalamomesencephalic junction and was
      associated with significant morbidity. However, the safety of the approach needs
      further validation. Neuronavigation is indicated to choose the most direct
      trajectory through the M1 perforators. Tractography may help protect the optic
      tract.

PMID- 18728607
TI  - Comparison of N-butyl cyanoacrylate and onyx for the embolization of intracranial
      arteriovenous malformations: analysis of fluoroscopy and procedure times.
AB  - OBJECTIVE: Intracranial arteriovenous malformations (AVM) may be managed through
      staged preoperative embolization and resection. Two commonly used liquid embolics
      are N-butyl cyanoacrylate (nBCA; Cordis Microvascular, Inc., New Brunswick, NJ)
      and Onyx (ev3, Inc., Irvine, CA). We sought to compare the utility of these
      agents in terms of fluoroscopy and procedure times. METHODS: All intracranial
      AVMs embolized from 2002 to 2006 at the University of Florida were included in
      this study. Patients were stratified into three treatment groups: nBCA, Onyx, and
      patients who received both nBCA and Onyx during separate embolizations. Cohorts
      were compared by sex, age, Spetzler-Martin grade, AVM volume, fluoroscopy time,
      procedure time, surgical blood loss, and complications. RESULTS: A total of 182
      embolizations were performed on 88 patients (nBCA, 60 patients and 106
      procedures; Onyx, 20 patients and 43 procedures; and nBCA/Onyx, eight patients
      and 16 nBCA and 17 Onyx procedures). There were no significant differences in
      patient demographics, AVM volumes, and Spetzler-Martin grades. Mean fluoroscopy
      and procedure times were increased for Onyx (57 min; 2.6 h) compared with nBCA
      (37 min; 2.1 h) embolizations (P < 0.0001 and P = 0.001, respectively).
      Cumulative mean fluoroscopy time was increased for Onyx (135 min) and nBCA/Onyx
      (180 min) cohorts relative to nBCA (64 min; P < 0.0001). Cumulative mean
      procedure time was increased in the nBCA/Onyx group (10.4 h) compared with nBCA
      (3.7 h) and Onyx (5.4 h; P < 0.0001). Seventy patients (80%) underwent AVM
      resection. No significant differences in surgical blood loss or complication
      rates were observed among the cohorts. CONCLUSION: Onyx AVM embolization requires
      increased fluoroscopy and procedure times compared with nBCA. Further
      investigation is necessary to justify increased radiation exposure and procedure
      time associated with Onyx.

PMID- 18728608
TI  - Radiation exposure during endovascular procedures.
AB  - OBJECTIVE: The duration of fluoroscopy exposure is routinely recorded as part of
      endovascular procedures. However, to better relate the duration of exposure to
      actual doses of surface and intracranial radiation, we compared surface doses
      during endovascular procedures with intracranial doses in a cadaver model exposed
      to lateral fluoroscopy. METHODS: Optically stimulated luminescence dosimeter
      chips (Landauer, Glenwood, IL) were used to measure the cranial surface dose of
      three consecutive patients undergoing endovascular procedures. Bitemporal
      craniotomies were performed on a cadaver. Dosimeter chips were placed on both the
      ipsilateral and contralateral skin and meningeal surfaces, and the cadaver was
      exposed to lateral fluoroscopy. Finally, to assess mean fluoroscopy times in
      patients undergoing embolization procedures, the operative notes of 100
      consecutive patients were reviewed. RESULTS: Three patients undergoing
      endovascular treatment received peak doses of 0.24, 0.31, and 1.38 Gy,
      respectively. In the cadaver, the peak surface dose recorded after 120 minutes of
      exposure was 1.71 Gy. The cranium and scalp absorbed or reflected 29% of the
      surface dose. Time in minutes of fluoroscopy was found to correlate with surface
      dose (R2 = 0.925). CONCLUSION: Our data show that radiation exposure during
      endovascular treatment can reach clinically significant levels. The surface doses
      recorded during this study were comparable to the mean dose of 1.5 Gy estimated
      by others to increase the relative risk of inducing meningiomas, gliomas, and
      nerve sheath tumors. Pending long-term follow-up of patients exposed to
      endovascular procedures, consent for possible long-term sequelae of radiation may
      be warranted.

PMID- 18728609
TI  - Open reduction of C1-C2 subluxation with the use of C1 lateral mass and C2
      translaminar screws.
AB  - OBJECTIVE: Spinal cord compression secondary to a subluxation of one vertebral
      body over another can be achieved with reduction of the translational deformity.
      Intraoperative reduction of C1-C2 subluxations can be technically challenging
      when one uses traditional techniques (e.g., wiring and transarticular screw
      fixation). The popularization of C1 lateral mass and C2 pedicle screws has
      allowed surgeons to achieve a more complex realignment at this region of the
      spine. Control of both C1 and C2 with independent fixation can be used to obtain
      reduction. In certain instances, placement of C2 pedicle screws is not possible.
      The use of C2 translaminar screws (if the C2 lamina is present and suitable) is
      an alternative method of fixation in C2 and can be used for intraoperative
      reduction. CLINICAL PRESENTATION: A 15-year-old boy with juvenile rheumatoid
      arthritis presented with spinal cord compression secondary to a C1-C2
      subluxation. The C2 pedicle anatomy precluded safe placement of C2 pedicle
      screws. An alternative method of fixation with the use of C2 translaminar screws
      and reduction was performed to obtain proper alignment and decompress the spinal
      cord. TECHNIQUE: C1 lateral mass screws and C2 translaminar screws are inserted
      in the usual fashion. Two contoured rods, two rod holders, and two distractors,
      combined with C1 lateral mass screws and C2 translaminar screws, were used to
      achieve reduction. Concomitant distraction between the C2 translaminar screw head
      and the rod holder resulted in ventral translation of C2 on C1, decompressing the
      spinal cord. The reduction was maintained by tightening the C2 locking nut onto
      the rod. CONCLUSION: The use of C2 translaminar screws (if the C2 lamina is
      present and suitable) is an alternative method of fixation in C2. C1 lateral mass
      and C2 translaminar screw fixation provide a powerful means of reducing C1-C2
      subluxations and maintaining alignment, achieving indirect decompression of the
      spinal cord.

PMID- 18728610
TI  - Posterior reduction and fixation of an unstable Jefferson fracture with C1
      lateral mass screws, C2 isthmus screws, and crosslink fixation: technical case
      report.
AB  - OBJECTIVE: We sought to describe a modified technique for the reduction and
      stabilization of unstable Jefferson fractures. CLINICAL PRESENTATION: We present
      the case of an isolated unstable Jefferson fracture in a 33-year-old woman. The
      patient was the victim of a motor vehicle accident. Her neurological examination
      was normal. A cervical computed tomographic scan revealed an isolated Jefferson
      fracture that we thought to be unstable when we applied the Spence criteria.
      TECHNIQUE: The fracture was treated by a technical variant of C1-C2 posterior
      fixation with compression on the rods by means of a crosslink connector, allowing
      the reduction of the atlantoaxial lateral mass overhanging. C1-C2 fusion with
      posterior iliac crest bone graft was added. CONCLUSION: The 1-year radiological
      follow-up evaluation showed a complete consolidation of the fracture lines and
      atlantoaxial stability. This technique could be an option for the reduction and
      stabilization of the unstable Jefferson fractures.

PMID- 18728611
TI  - Minimally invasive thoracoscopic resection of paraspinal neurogenic tumors:
      technical case report.
AB  - OBJECTIVE: The posterior mediastinum is a common location for benign neurogenic
      tumors. They are frequently asymptomatic but can present with local compressive
      or neurological symptoms. METHODS: Thoracoscopy is used increasingly over
      posterolateral thoracotomy for the removal of these lesions. RESULTS: Complete
      resection of these tumors through a thoracoscopic approach is possible in most
      cases, but dumbbell tumors present as special challenges, which require a
      combined thoracoscopic and open posterior approach. CONCLUSION: In this article,
      we outline the technique of thoracoscopic resection of paraspinal neurogenic
      tumors through an operative video and a review of the literature to summarize the
      surgical outcomes of patients with these lesions.

PMID- 18728612
TI  - Carotid artery stenting under flow arrest for the management of intraluminal
      thrombus: technical case report.
AB  - OBJECTIVE: The management of intraluminal carotid thrombus is not well defined.
      Medical and surgical management carry a relatively high risk of thromboembolism.
      Although endovascular options also carry the risk of thromboembolism from
      manipulation of the lesion, successful carotid stent placement using various
      methods of flow restriction has been reported anecdotally. We describe a
      technique to arrest antegrade flow before placement of carotid stents in the
      setting of symptomatic intraluminal thrombus. CLINICAL PRESENTATION: A 49-year
      old woman presented with expressive dysphasia, right-upper extremity weakness,
      and an episode of left monocular blindness. Angiography confirmed the presence of
      a large intraluminal thrombus in a chronic dissection of the left internal
      carotid artery. RESULTS: We devised a configuration to arrest antegrade flow in
      the internal carotid artery before crossing the thrombus with a distal embolic
      protection device by inflating balloons in the common carotid artery and external
      carotid artery before crossing the lesion. After inflation of a balloon in the
      internal carotid artery, we completed overlapping stent placement to completely
      exclude the thrombus from the lumen. CONCLUSION: The patient remained
      neurologically unchanged during and immediately after the procedure. She had mild
      neurological deficits at the 1 month follow-up evaluation. Follow-up
      ultrasonography at 1 and 3 months and computed tomographic angiography at 3
      months after the procedure showed patency of the stented carotid artery, with no
      evidence of restenosis or thrombus. Although the risks of carotid stent placement
      for intraluminal thrombus remain unclear, the technique of flow arrest seems to
      provide a safe endovascular treatment option.

PMID- 18728613
TI  - Monorail snare technique for the retrieval of an adherent microcatheter from an
      onyx cast: technical case report.
AB  - OBJECTIVE: Microcatheters retained after Onyx (eV3 Neurovascular, Inc., Irvine,
      CA) embolization represent a potential source of thromboembolic complications.
      Catheter retention depends on the degree of Onyx reflux and vessel tortuosity. To
      overcome this problem, we have adapted a previously described monorail snare
      technique for stretched coils to remove an adherent microcatheter from the
      occipital artery during Onyx embolization of a dural arteriovenous fistula.
      CLINICAL PRESENTATION: We used this technique successfully in a 62-year-old man
      with a posterior fossa dural arteriovenous fistula. An Echelon-10 microcatheter
      (eV3 Neurovascular, Inc.) system became adherent in the right occipital artery
      because of reflux and vessel tortuosity. Significant stretching of the
      microcatheter was observed during attempted removal. INTERVENTION: A 2-mm Amplatz
      Goose Neck microsnare (Microvena Corp., White Bear Lake, MN) was placed through a
      Rapid Transit microcatheter (Cordis Corp., Miami, FL). The hub of the indwelling
      Echelon microcatheter was cut off and the snare advanced over the outside of the
      microcatheter. The snare and Rapid Transit microcatheter were then advanced into
      the guiding catheter (6-French) as a unit over the indwelling Echelon
      microcatheter. Using the adherent Echelon as a "monorail" guide, the snare and
      Rapid Transit microcatheter were advanced distally into the occipital artery and
      the snare was retracted to engage the microcatheter. The microcatheters and snare
      were then easily removed because of the second vector of force placed by the
      snare system on the adherent microcatheter very close to the point of adherence.
      CONCLUSION: The monorail snare technique represents a simple and safe way to
      remove an adherent microcatheter from an Onyx cast during the embolization of
      dural arteriovenous fistulas. Prospective knowledge of this technique will
      facilitate more aggressive embolization without the reservation that a retained
      microcatheter could require surgical removal or anticoagulation.

PMID- 18728614
TI  - A useful side-hole on a guiding catheter for transvenous embolization of a
      transverse-sigmoid sinus dural arteriovenous fistula.
AB  - OBJECTIVE: To report the usefulness of a side-hole on a guiding catheter for
      transvenous embolization of transverse-sigmoid sinus (TSS) dural arteriovenous
      fistulae (DAVF) by a contralateral approach with a reversed Y-shaped confluence.
      CLINICAL PRESENTATION: A 66-year-old woman presented after an epileptic seizure.
      Magnetic resonance imaging revealed venous infarctions of the left temporal area.
      Angiography showed a DAVF in the left TSS with retrograde drainage toward the
      superior sagittal sinus and remarkable cortical reflux. INTERVENTION: A
      transvenous approach through the right jugular vein was attempted after failure
      of the approach through the angiographically invisible left jugular vein.
      Catheterization beyond the confluence failed because the shape of the confluence
      was a reversed Y. A 5-French catheter with a side-hole was then placed in the
      superior sagittal sinus from the right TSS, and the microcatheter was
      successfully navigated into the left TSS through the side-hole. Subsequently, the
      DAVF was completely occluded by transvenous embolization without any adverse
      events. CONCLUSION: A side-hole on a guiding catheter was found to be useful for
      the navigation of a microcatheter to override a reversed Y-shaped confluence in
      transvenous embolization of TSS DAVF. This technique could be applicable to
      difficult configurations for transvenous catheterization, although attention
      should be paid to disruption of the catheter.

PMID- 18728615
TI  - Endoscopic transnasal transclival odontoidectomy: a new approach to
      decompression: technical case report.
AB  - OBJECTIVE: Endoscopic transnasal transclival resection of the odontoid process is
      less invasive than the standard transoral odontoidectomy. In this article, we
      describe our techniques, which are less invasive but provide successful
      decompression. CLINICAL PRESENTATION: From September 2004 to April 2007, three
      consecutive patients with basilar invagination and instability in the
      craniovertebral junction were enrolled. The causes for the invagination and
      instability included rheumatoid arthritis in two patients and trauma in one
      patient, and all patients presented with myelopathy and quadriparesis before
      intervention. INTERVENTION: All three patients underwent an endoscopic transnasal
      transclival approach for anterior decompression and resection of the displaced
      odontoid process and pannus to decompress the underlying medulla. Subsequently,
      they received occipitocervical fixation by lateral mass screws and bone fusion to
      ensure stability. Remarkable neurological recovery was observed after surgery in
      all patients, and no adverse effects were noted. CONCLUSION: Compared with the
      standard transoral approach, the transnasal transclival endoscopic approach for
      decompressing basilar invagination is a feasible and effective alternative that
      avoids common disadvantages like prolonged intubation, excessive tongue
      retraction, and the need for palatal incision.

PMID- 18728616
TI  - Fibrovascular membrane removal using a high-performance 25-gauge vitreous cutter.

PMID- 18728617
TI  - Corneoscleral necrosis after episcleral Au-198 brachytherapy of uveal melanoma.
AB  - PURPOSE: To describe the risk factors for the development of corneoscleral
      necrosis (CSN) and its management in patients with primary choroidal or
      ciliochoroidal melanoma who underwent episcleral Au-198 brachytherapy. METHODS:
      Clinical records of patients with symptoms of dry eye, foreign body sensation,
      pain, and evidence of CSN after Au-198 brachytherapy for uveal melanoma treated
      over a 22-year period were reviewed retrospectively. Risk factors for the
      development of CSN were identified and various methods of management were
      evaluated. The data were analyzed using multivariant analysis. A P < 0.05 was
      taken as a level of statistical significance. RESULTS: Of the 202 eyes of 202
      patients treated with Au-198 radioactive plaque, 15 (7.4%) patients with
      symptomatic complaints of dry eye and pain showed evidence of CSN. First signs
      were noted as early as 1 month to as late as 5 years (median time 5 months) after
      the treatment. Risk factors for the development of CSN included tumor thickness
      greater than 6 mm and ciliary body involvement (P < 0.05). Associated risk factor
      included intraocular pressure greater than 21 mmHg. Four patients required
      conservative management, 11 patients required scleral patch and/or conjunctival
      flaps, and 6 eyes eventually required enucleation. Eyes which developed CSN were
      more likely to undergo enucleation compared with eyes having no evidence of CSN
      (P < 0.05). None of the eyes with CSN, which required enucleation because of the
      failed treatment, had histopathologic evidence of recurrent tumor or tumor
      invading sclera. CONCLUSION: Corneoscleral necrosis may occur soon or several
      years after Au-198 brachytherapy for uveal melanoma. Risk factors for CSN include
      tumor thickness greater than 6 mm, ciliary body involvement, and intraocular
      pressure >21 mmHg. Closer follow-up, early recognition, and timely intervention
      may avert serious consequences.

PMID- 18728618
TI  - Ocular decompression retinopathy after anterior chamber paracentesis for uveitic
      glaucoma.

PMID- 18728619
TI  - Carcinoma-associated retinopathy-an electrophysiological and immunohistochemical
      correlation.
AB  - PURPOSE: To correlate the clinical, electrophysiological, and immunohistochemical
      findings in patients suffering from carcinoma-associated retinopathy. METHODS:
      Four patients with visual loss were included in this retrospective, observational
      consecutive case series. Electrophysiology and immunohistochemical analysis were
      performed to confirm the diagnosis of carcinoma-associated retinopathy. RESULTS:
      Immunohistochemistry revealed a marked interindividual variability of antibody
      reactions against different retinal cell layers of individual patients. The
      electrophysiological changes corresponded to the respective immunohistochemical
      findings. CONCLUSION: Carcinoma-associated retinopathy is a heterogeneous
      disease, caused by different antiretinal antibodies and leading to different
      electrophysiological abnormalities. Diagnosis should not be delayed as undetected
      and thus untreated malignancy can be the cause.

PMID- 18728620
TI  - Transconjunctival 25-gauge sutureless vitrectomy and silicone oil injection in
      diabetic tractional retinal detachment.
AB  - PURPOSE: The purpose of this article was to evaluate the outcomes and
      complications of transconjunctival sutureless 25-gauge vitrectomy using silicone
      oil tamponade in diabetic tractional retinal detachment. MATERIALS AND METHODS:
      Patients were retrospectively evaluated. Main outcome measure was the feasibility
      of pars plana vitrectomy and silicone oil injection with 25-gauge system in eyes
      with diabetic tractional retinal detachment. RESULTS: Fourteen eyes of 14
      patients were included in the study. Tractional retinal detachment was
      accompanied by vitreous hemorrhage in 9 eyes and combined traction/rhegmatogenous
      retinal detachment was present in 1 eye. All patients underwent transconjunctival
      sutureless 25-gauge vitrectomy and 1,000 centistokes silicone oil injection.
      Angled insertion of the trocars was made in all eyes. Bimanual surgery was
      performed in 6 (42.8%) eyes. The median preoperative best-corrected visual
      acuities were 3.00 logarithm of the minimum angle of resolution; it increased to
      1.60 logarithm of the minimum angle of resolution at last visit. Retinal tear
      formation occurred in 4 (28.5%) eyes. Retinal detachment developed in 2 (14.2%)
      eyes. Intraocular pressure of 5 mmHg or less was detected in 3 (21.4%) eyes. One
      patient lost light perception due to anterior hyaloidal fibrovascular
      proliferation. CONCLUSION: Pars plana vitrectomy and 1,000 centistokes silicone
      oil injection with 25-gauge system is feasible in diabetic tractional retinal
      detachment even in complex cases. Indications of 25-gauge surgery may be expanded
      toward this area.

PMID- 18728621
TI  - Repeated intravitreal injection of bevacizumab for clinically significant
      diabetic macular edema.
AB  - PURPOSE: Intravitreal bevacizumab (Avastin) induces a transient improvement in
      diabetic macular edema, necessitating repeated injections. Here, we report the
      results of repeated administration of intravitreal bevacizumab for the treatment
      of clinically significant macular edema in 31 eyes of 24 patients. METHODS: At
      preinjection and 1, 6, and 12 (+/-1) weeks postinjection, visual acuity (VA) with
      Early Treatment of Diabetic Retinopathy Study (ETDRS) and central macular
      thickness (CMT) evaluated using optical coherence tomography were compared with
      independent and paired t-tests. RESULTS: VA and CMT were not significantly
      different before initial and repeated injections (administered at an interval of
      22.06 +/- 11.15 [SD] weeks). At 6 weeks after the first injection, VA increased
      significantly by 3.72 +/- 8.02 ETDRS letters (P = 0.019), and CMT was markedly
      decreased by 93.30 +/- 210.33 microm (P = 0.022), which returned to near baseline
      at 12 weeks. At 6 weeks after the second injection, VA increased significantly by
      3.97 +/- 7.46 ETDRS letters (P = 0.006) and CMT decreased considerably by 118.77
      +/- 178.58 microm (P = 0.001). At 12 weeks after the second injection, we
      observed a decrease in VA with recurrence of macular edema. CONCLUSIONS: Repeated
      administration of intravitreal bevacizumab (1.25 mg) may lead to the improvement
      of VA and CMT in patients with clinically significant macular edema.

PMID- 18728623
TI  - Changes in aqueous vascular endothelial growth factor and pigment epithelial
      derived factor levels following intravitreal bevacizumab injections for choroidal
      neovascularization secondary to age-related macular degeneration or pathologic
      myopia.
AB  - BACKGROUND: To evaluate the changes in aqueous vascular endothelial growth factor
      (VEGF) and pigment epithelium-derived factor (PEDF) following intravitreal
      bevacizumab injections for choroidal neovascularization (CNV) secondary to age
      related macular degeneration or pathologic myopia. METHODS: Aqueous samples were
      obtained at the time of injection from 51 eyes of 51 patients who underwent three
      monthly intravitreal bevacizumab (Avastin) injections at baseline, 1, and 2
      months. Concentrations of VEGF and PEDF in the aqueous were evaluated using
      enzyme-linked immunosorbent assay and compared. RESULTS: For the 34 eyes with age
      related macular degeneration CNV, the mean +/- standard deviation aqueous VEGF
      level reduced from 102.6 pg/mL +/- 90.6 pg/mL at baseline to 18.3 pg/mL +/- 22.5
      pg/mL at 2 months (P < 0.001), whereas the mean PEDF level increased from 11.2
      ng/mL +/- 10.4 ng/mL at baseline to 38.7 ng/mL +/- 47.9 ng/mL at 2 months (P =
      0.001). For the 17 eyes with myopic CNV, the mean +/- standard deviation aqueous
      VEGF level reduced from 20.1 pg/mL +/- 28.9 pg/mL at baseline to 3.8 pg/mL +/-
      5.3 pg/mL at 2 months (P = 0.016), whereas the mean PEDF level increased from
      20.0 ng/mL +/- 16.3 ng/mL at baseline to 126.0 ng/mL +/- 152.0 ng/mL at 2 months
      (P = 0.016). CONCLUSIONS: Intravitreal bevacizumab injections resulted in reduced
      aqueous VEGF and increased PEDF levels in patients with CNV secondary to age
      related macular degeneration or pathologic myopia. These changes may be favorable
      for the inhibition of CNV angiogenesis.

PMID- 18728624
TI  - Demarcation laser photocoagulation of macular sparing retinal detachments in
      teenagers.
AB  - PURPOSE: To report a series of macular sparing rhegmatogenous retinal detachment
      (MSRRD) in teenagers treated with demarcation laser photocoagulation. METHODS:
      Retrospective, interventional, and noncomparative case series of 36 eyes in 33
      patients with primary MSRRD. Eyes with ocular congenital anomalies or perforation
      ocular injury were excluded from this study. All eyes received three or more rows
      of confluent demarcation laser photocoagulation at the margin of retinal
      detachment. Best corrected preoperative and postoperative visual acuity and
      progression of retinal detachment during the follow-up were recorded. RESULTS:
      Thirty two eyes needed only one session of laser to wall off the retinal
      detachment. The other four eyes required one additional laser because of
      progressive retinal detachment. All but one eye had shallow retinal detachment
      and retinal detachment was successfully demarcated after 1 or 2 episodes of laser
      treatment at the final visit. Patients were observed up at our clinic from 1 to 6
      years. Myopia greater than -3 D was noted in all but one eye. Atrophic holes with
      or without lattice were the causative breaks in all eyes. All patients maintained
      best corrected visual acuity equal or better than 20/30. CONCLUSION: Demarcation
      laser could successfully wall off macular sparing retinal detachment in
      teenagers.

PMID- 18728625
TI  - Role of prednisolone pharmacokinetics in postchallenge glycemia after renal
      transplantation.
AB  - Prednisolone may cause hyperglycemia after organ transplantation. Even at
      comparable weight-adjusted doses, prednisolone side effects vary considerably
      between individuals, suggesting between-patient pharmacokinetic differences. In
      renal transplant patients, assessment of glucocorticoid diabetogenicity is
      confounded by calcineurin inhibitors (CNIs). The present study aimed to
      investigate, in a CNI-free setting, the association between exposure to unbound
      prednisolone and glucose tolerance in stable nondiabetic long-term renal
      transplant patients. An oral glucose tolerance test and a 12-hour prednisolone
      pharmacokinetic study were performed in 108 nondiabetic CNI-naive subjects (41
      women and 67 men) treated with prednisolone (median 0.15 mg kg d, interquartile
      range 0.14-0.18 mg kg d) and azathioprine. The area under the curve (AUC) of
      unbound prednisolone was analyzed in multiple linear regression analysis with 120
      minute postchallenge glucose AUC as the dependent variable. A high AUC of unbound
      serum prednisolone was independently associated with a high glucose AUC (P =
      0.030). A high glucose AUC was also associated with a high patient age and
      triglyceride level (both P < or = 0.001). No correlation was observed between the
      daily prednisolone dosage (mg/d or mg kg d) and glucose AUC. The association
      between exposure to unbound prednisolone and postchallenge glycemia is in line
      with current knowledge about mechanisms behind steroid-related side effects but
      has not previously been documented. The result may argue in favor of measuring
      unbound prednisolone in clinical settings. Increasing exposure to unbound
      prednisolone was independently associated with postchallenge glycemia. No such
      relationship was observed for prednisolone daily dose per se.

PMID- 18728626
TI  - Quantity as an expression of quality: relationship between serum drug
      concentrations and quality of life.
AB  - A recent study has demonstrated an inverse correlation between serum valproic
      acid concentration in adolescents with epilepsy and quality of life, suggesting
      that cognitive and behavioral effects of anticonvulsants may significantly impact
      the life of patients with epilepsy and that intensive therapeutic drug monitoring
      may have a role in both reducing seizure frequency and improving health-related
      quality of life.

PMID- 18728627
TI  - Trough concentrations of lopinavir, nelfinavir, and nevirapine with standard
      dosing in human immunodeficiency virus-infected pregnant women receiving 3-drug
      combination regimens.
AB  - The objective of this study was to evaluate the plasma drug concentrations in
      human immunodeficiency virus (HIV)-infected pregnant women receiving highly
      active antiretroviral therapy (HAART) and to define the rate of occurrence of
      subtherapeutic concentrations for some commonly used antiretroviral drugs during
      pregnancy. We evaluated HIV-infected women (n = 68) in the third trimester of
      pregnancy in steady-state treatment with an HAART regimen administrated on a
      twice a day basis, which included 2 nucleoside reverse transcriptase inhibitors
      plus nelfinavir (NFV), lopinavir/ritonavir (LPV/r), or nevirapine (NVP). Blood
      samples were collected at predose (C(trough)). The following thresholds were used
      to define therapeutic drug concentrations-NFV: 0.8 microg/mL; LPV: 4.0
      microg/mL/1.0 microg/mL (experienced/naive); and NVP: 3.1 microg/mL. At predose
      sampling, adequate drug concentrations were found in a higher proportion of women
      receiving NFV (70.8%) and LPV (75.0%) than NVP (55.6%). Median C(trough) plasma
      concentrations were 1.2 microg/mL for NFV, 5.5 microg/mL for LPV, and 3.1
      microg/mL for NVP. Women receiving lopinavir/ritonavir had the lowest rates of
      detectable (>50 copies/mL) HIV RNA (15.4%) compared with rates of 22.2% and 41.7%
      among women receiving NVP and NFV, respectively. Genotypic resistance was
      detected in 50% of women with detectable HIV RNA for whom samples were available
      for testing. Subtherapeutic predose concentrations among HIV-infected pregnant
      women were more commonly found with NVP than with protease inhibitors. LPV
      administration was associated with the best viral load suppression.

PMID- 18728628
TI  - Impact of multiple inhibitors or substrates of cytochrome P450 2D6 on plasma
      risperidone levels in patients on polypharmacy.
AB  - Studies that focus on multidrug interactions in natural settings are sparse. In
      this investigation, data from therapeutic drug monitoring (TDM) were used to
      study the impact of multiple cytochrome P450 enzyme (CYP) 2D6 substrates and
      inhibitors on plasma risperidone levels. CYP2D6 catalyzes the conversion of
      risperidone to the active metabolite 9-OH-risperidone. The question whether
      CYP2D6 activity is important for the level of the "active moiety" (ie, the sum of
      risperidone and 9-OH-risperidone) is controversial. Concentration-to-dose (C:D)
      ratios of risperidone and 9-OH-risperidone in 218 patients were associated with
      the number of concomitantly used substrates or inhibitors of CYP2D6. The C:D
      ratios of risperidone in patients with 0, 1, and >1 numbers of CYP2D6 inhibitors
      were 2.6, 8.5, and 17 nmol L mg, respectively. Differences between the groups
      were highly significant (P < 0.001). All patients with >1 CYP2D6 inhibitors were
      administered at least 1 potent CYP2D6 inhibitor, that is fluoxetine, paroxetine,
      thioridazine, and/or levomepromazine. The C:D ratios of the active moiety
      (risperidone + 9-OH-risperidone) in patients with 0, 1, and >1 numbers of
      concomitant CYP2D6 inhibitors were 17, 24, and 30 nmol L mg, respectively (P =
      0.001), which was explained by higher levels of risperidone without any change in
      the levels of 9-OH-risperidone. Concomitant use of 1 or several drugs recognized
      as substrates for CYP2D6, without any proven inhibitory effect, had no apparent
      influence on the levels of risperidone or 9-OH-risperidone, suggesting that the
      risk of drug-drug interactions between different substrates of CYP2D6 is low when
      used in therapeutic doses. In conclusion, the results suggest that an increase in
      the number of concomitant inhibitors may be associated with a lower CYP2D6
      activity, although the type of inhibitor is probably more important. Drug
      dependent inhibition of CYP2D6 increases the active moiety of risperidone. An
      indication for risperidone TDM should therefore include concomitant medication
      with established CYP inhibitors.

PMID- 18728629
TI  - Does the probiotic L. casei help prevent recurrence after transurethral resection
      for superficial bladder cancer?

PMID- 18728630
TI  - Should patients with muscle-invasive bladder cancer undergo more-extensive pelvic
      lymph node dissection?

PMID- 18728631
TI  - Which nonsurgical options are effective for the treatment of female urinary
      incontinence?

PMID- 18728632
TI  - MicroRNAs, the immune system and rheumatic disease.
AB  - MicroRNAs (miRNAs) are short noncoding RNA molecules that modulate the expression
      of multiple target genes at the post-transcriptional level and are implicated in
      a wide array of cellular and developmental processes. In hematopoietic cells,
      miRNA levels are dynamically regulated during lineage differentiation and also
      during the course of the immune response. Mouse models have provided good
      evidence for miRNAs being key players in the establishment of hematopoietic
      lineages. Furthermore, miRNA-dependent alterations in gene expression in
      hematopoietic cells are critical for mounting an appropriate immune response to a
      wide range of pathogens, spontaneously emerging tumors, and autoimmune cells.
      Deregulation of hematopoietic-specific miRNA expression results in defects in
      both central and peripheral tolerance, hematopoietic malignancies, and sometimes
      both. Abnormal expression of miRNAs-which is implicated in inflammation-has also
      been found in patients with rheumatoid arthritis. These findings identify miRNAs
      as critical targets for immunomodulatory drug development.

PMID- 18728633
TI  - The ISN Clinical Practice Guidelines Committee.

PMID- 18728634
TI  - Treatment of acute kidney injury in children: from conservative management to
      renal replacement therapy.
AB  - Over the past two decades, the etiology and therapy of acute kidney injury (AKI)
      in children has changed. Historically, hemolytic uremic syndrome was the major
      cause of pediatric AKI, but advances in technology have meant that sepsis and
      deterioration of often unrecognized long-term organ dysfunction are now more
      common causes of pediatric AKI in the developed world. At the same time, major
      advances in renal replacement therapy in children have occurred as a result of
      improved strategies for vascular access, more-adaptable equipment, and better
      techniques and protocols. This Review outlines the etiology, incidence,
      diagnosis, and treatment--both dialytic and non-dialytic--of pediatric AKI.

PMID- 18728635
TI  - Tailoring T-cell receptor signals by proximal negative feedback mechanisms.
AB  - The T-cell receptor (TCR) signalling machinery is central in determining the
      response of a T cell (establishing immunity or tolerance) following exposure to
      antigen. This process is made difficult by the narrow margin of self and non-self
      discrimination, and by the complexity of the genetic programmes that are induced
      for each outcome. Recent studies have identified novel negative feedback
      mechanisms that are rapidly induced by TCR engagement and that have key roles in
      the regulation of signal triggering and propagation. In vitro and in vivo data
      suggest that they are important in determining ligand discrimination by the TCR
      and in regulating signal output in response to antigen.

PMID- 18728636
TI  - The X-files in immunity: sex-based differences predispose immune responses.
AB  - Despite accumulating evidence in support of sex-based differences in innate and
      adaptive immune responses, in the susceptibility to infectious diseases and in
      the prevalence of autoimmune diseases, health research and clinical practice do
      not address these distinctions, and most research studies of immune responses do
      not stratify by sex. X-linked genes, hormones and societal context are among the
      many factors that contribute to disparate immune responses in males and females.
      It is crucial to address sex-based differences in disease pathogenesis and in the
      pharmacokinetics and pharmacodynamics of therapeutic medications to provide
      optimal disease management for both sexes.

PMID- 18728637
TI  - Therapeutic efficacy of a herpes simplex virus with radiation or temozolomide for
      intracranial glioblastoma after convection-enhanced delivery.
AB  - The herpes simplex virus-1 (HSV-1)-infected cell protein 0 (ICP0) is an E3
      ubiquitin ligase implicated in cell cycle arrest and DNA repair inhibition.
      Convection-enhanced delivery (CED) of either the replication-defective, ICP0
      producing HSV-1 mutant, d106, or the recombinant d109, devoid of all viral genome
      expression, was performed to determine the in vivo efficacy of ICP0 in
      combination with ionizing radiation (IR) or systemic temozolomide (TMZ) in the
      treatment of glioblastoma multiforme (GBM). Intracranial U87-MG xenografts were
      established in athymic nude mice. Animal survival was determined after mice
      underwent intracranial CED of either the replication-defective d106 or d109
      viruses, or Hanks' balanced salt solution (HBSS), before a single session of
      whole-brain irradiation or TMZ treatment. Median survival for animals that
      underwent treatment with HBSS alone, d109 alone, d106 alone, HBSS + IR, HBSS +
      TMZ, d109 + IR, d106 + IR, and d106 + TMZ was 28, 35, 41, 39, 44, 39, 68 (P <
      0.01), and 66 days (P < 0.01), respectively. Intracerebral d106 CED resulted in a
      significant increase in athymic nude mouse survival when combined with IR or TMZ.
      d106 CED allows for distribution of HSV-1 in human GBM xenografts and persistent
      viral infection.

PMID- 18728638
TI  - Whole animal in vivo imaging after transient, nonviral gene delivery to the rat
      central nervous system.
AB  - We previously showed that a vector:lipid delivery system, comprised of a plasmid
      DNA vector and cationic lipid (lipoplex), when injected into the cerebrospinal
      fluid (CSF) of rats can deliver reporter genes in vivo efficiently and with
      widespread expression to the Central Nervous System (CNS). To further
      characterize this delivery system, we now present experiments that demonstrate
      the in vivo time-to-peak expression of the reporter gene, firefly luciferase. We
      infused a formulated lipoplex containing the lipid MLRI [dissymmetric myristoyl
      (14:0) and lauroyl (12:1) rosenthal inhibitor-substituted compound formed from
      the tetraalkylammonium glycerol-based DORI] and pNDluc, a luciferase vector, into
      CSF in the cisterna magna (CM) of the rat. Luciferase activity was followed over
      time by bioluminescence imaging after injection of luciferin. Our results show
      that luciferase activity in the CNS of rats is widespread, peaks 72 hours after
      injection into CM and can be detected in vivo for at least 7-10 days after peak
      expression. We further show that in contrast to injection into CSF, enzyme
      activity is not widely distributed after injection of the vector into brain
      parenchyma, emphasizing the importance of CSF delivery to achieve widespread
      vector distribution. Finally, we confirm the distribution of firefly luciferase
      in brain by immunohistochemical staining from an animal that was euthanized at
      the peak of enzyme expression.

PMID- 18728639
TI  - Transgene expression, bioactivity, and safety of CERE-120 (AAV2-neurturin)
      following delivery to the monkey striatum.
AB  - Neurturin (NTN) is a neurotrophic factor for dopaminergic neurons that may be
      therapeutic for patients with Parkinson's disease (PD). As a crucial component in
      a series of nonclinical translational studies aimed at testing whether CERE-120
      should advance into clinical trials in PD subjects, we characterized the
      expression, bioactivity and safety of CERE-120, an adeno-associated virus type-2
      (AAV2) vector encoding NTN, following delivery to the striatum of nonhuman
      primates. Monkeys received bilateral injections of CERE-120 across a tenfold
      range of doses (6 x 10(10) to 6 x 10(11) vector genomes per animal) or
      formulation buffer (FB) control. We report here, for the first time, a dose
      related: increase in NTN protein expression within the striatum and substantia
      nigra (SN) pars compacta of nonhuman primates; increase in nigrostriatal tyrosine
      hydroxylase (TH), (the rate-limited enzyme for dopamine); and activation of
      phosphorylated signal-regulated kinase (a common neurotrophic signaling event).
      Additionally, extensive toxicology testing revealed no adverse effects of CERE
      120 on in-life measures, neurotoxicity (in any site throughout the brain) or
      systemic pathology (in any organ or tissue) across the tenfold range of doses.
      Collectively, these data provide substantial novel evidence for the potential
      utility of CERE-120 as a novel treatment for PD and support ongoing clinical
      trials testing CERE-120 in PD patients.

PMID- 18728641
TI  - Chemotherapy targeted to cancer tissue potentiates antigen-specific immune
      response induced by vaccine for in vivo antigen loading and activation of
      dendritic cells.
AB  - Our laboratory has created an Ad-sig-TAA/ecdCD40L vaccine platform designed to
      activate dendritic cells (DCs). Two subcutaneous (s.c.) injections of the
      TAA/ecdCD40L protein following the s.c. injection of the Ad-sig-TAA/ecdCD40L
      vector (TAA/ecdCD40L VPP vaccine) further increases the levels of the tumor
      associated antigen (TAA)-specific CD8 effector T cells induced by the vector. We
      tested the combined effect of chemotherapy-induced destruction of tumor cells and
      TAA/ecdCD40L VPP vaccine which further increases the levels of TAA available to
      the DCs at the time of vaccination. The chemotherapy was delivered selectively to
      the tumor cells using intratumoral (i.t.) injection of the AdCDIRESE1A vector
      followed by intraperitoneal (i.p.) 5-fluorocytosine (5FC). The 5-fluorouracil
      (5FU) produced in the vector infected the tumor cells, destroys them and releases
      the TAA for processing and presentation by the DCs. This mode of delivery spares
      the TAA CD8 effector T cells from the destructive effect of the 5FU when their
      proliferation is induced by the vaccine. Test mice treated with both the s.c.
      administered TAA/ecdCD40L VPP vaccine and the AdCDIRESE1A/5FC chemosensitization
      vector had the smallest tumor volumes and survived longer than mice treated with
      either of these agents alone (P < 0.001).

PMID- 18728640
TI  - DNA shuffling of adeno-associated virus yields functionally diverse viral
      progeny.
AB  - Adeno-associated virus (AAV) vectors are extremely effective gene-delivery
      vehicles for a broad range of applications. However, the therapeutic efficacy of
      these and other vectors is currently limited by barriers to safe, efficient gene
      delivery, including pre-existing antiviral immunity, and infection of off-target
      cells. Recently, we have implemented directed evolution of AAV, involving the
      generation of randomly mutagenized viral libraries based on serotype 2 and high
      throughput selection, to engineer enhanced viral vectors. Here, we significantly
      extend this capability by performing high-efficiency in vitro recombination to
      create a large (10(7)), diverse library of random chimeras of numerous parent AAV
      serotypes (AAV1, 2, 4-6, 8, and 9). In order to analyze the extent to which such
      highly chimeric viruses can be viable, we selected the library for efficient
      viral packaging and infection, and successfully recovered numerous novel
      chimeras. These new viruses exhibited a broad range of cell tropism both in vitro
      and in vivo and enhanced resistance to human intravenous immunoglobulin (IVIG),
      highlighting numerous functional differences between these chimeras and their
      parent serotypes. Thus, directed evolution can potentially yield unlimited
      numbers of new AAV variants with novel gene-delivery properties, and subsequent
      analysis of these variants can further extend basic knowledge of AAV biology.

PMID- 18728642
TI  - Stable transgene expression from HSV amplicon vectors in the brain: potential
      involvement of immunoregulatory signals.
AB  - The herpes simplex virus (HSV) amplicon is a plasmid-based, infectious gene
      delivery system that carries up to 150 kilobase (kb) of exogenous DNA. We
      previously characterized early host responses and stability of transgene
      expression in mice systemically injected with HSV amplicon vectors. Transgene
      expression was readily detected primarily in the liver but rapidly declined to
      undetectable levels within 2 weeks. Molecular analyses revealed induction of type
      I interferons (IFN) as the primary response, and early transcriptional silencing
      of the vector followed IFN's activation of signal transducers and activators of
      transcription 1 (STAT1). In this study, we investigate vector administration by
      stereotactic injection into the striatum. In the brain, induction of type I IFN
      was rather modest, and transgene expression lasted more than 1 year despite dose
      dependent inflammation and infiltration of immune cells around injection sites.
      Further analyses revealed dose-dependent upregulation of immunosuppressive
      cytokines and molecular markers specific to regulatory T cells in the injected
      brain regions, which supported the immune-privileged properties of the brain
      parenchyma. Overall, our findings indicate that the spectrum of host responses
      can differ significantly depending on target organs and administrative routes,
      and that HSV amplicon vectors hold great potential for gene therapy of chronic
      neurological disorders.

PMID- 18728645
TI  - Can weight loss prevent cancer?
AB  - We review and update evidence on obesity, weight gain and weight loss in relation
      to leading cancers since the International Agency for Research on Cancer report
      of 2002. Emphasis is placed on the time course of disease and implications for
      weight control to prevent cancer. We conclude that weight loss could prevent a
      major portion of common cancers.

PMID- 18728643
TI  - A randomised phase II trial of preoperative chemotherapy of cisplatin-docetaxel
      or docetaxel alone for clinical stage IB/II non-small-cell lung cancer results of
      a Japan Clinical Oncology Group trial (JCOG 0204).
AB  - Preoperative chemotherapy is a promising strategy in patients with early-stage
      resectable non-small-cell lung cancer (NSCLC); optimal chemotherapy remains
      unclear. Clinical (c-) stage IB/II NSCLC patients were randomised to receive
      either two cycles of docetaxel (D)-cisplatin (P) combination chemotherapy (D 60
      mg m(-2) and P 80 mg m(-2) on day 1) every 3-4 weeks or three cycles of D
      monotherapy (70 mg m(-2)) every 3weeks. Thoracotomy was performed 4-5 weeks (DP)
      or 3-4 weeks (D) after chemotherapy. The primary end point was 1-year disease
      free survival (DFS). From October 2002 to November 2003, 80 patients were
      randomised. Chemotherapy toxicities were mainly haematologic and well tolerated.
      There were two early postoperative deaths with DP (one intraoperative bleeding
      and one empyema). Pathologic complete response was observed in two DP patients.
      Docetaxel-cisplatin was superior to D in terms of response rate (45 vs 15%) and
      complete resection rate (95 vs 87%). Both DFS and overall survival were better in
      DP. Disease-free survival at 1, 2 and 4 years were 78, 65 and 57% with DP, and
      were 62, 44 and 36% with D, respectively. Preoperative DP was associated with
      encouraging resection rate and DFS data, and phase III trials for c-stage IB/II
      NSCLC are warranted.

PMID- 18728655
TI  - Norman Bleehen.

PMID- 18728653
TI  - Dietary glycaemic index, glycaemic load and breast cancer risk: a systematic
      review and meta-analysis.
AB  - This systematic review aimed to examine if an association exists between dietary
      glycaemic index (GI) and glycaemic load (GL) intake and breast cancer risk. A
      systematic search was conducted in Medline and Embase and identified 14 relevant
      studies up to May 2008. Adjusted relative risk estimates comparing breast cancer
      risk for the highest versus the lowest category of GI/GL intake were extracted
      from relevant studies and combined in meta-analyses using a random-effects model.
      Combined estimates from six cohort studies show non-significant increased breast
      cancer risks for premenopausal women (relative risk (RR) 1.14, 95% CI 0.95-1.38)
      and postmenopausal women (RR 1.11, 95% CI 0.99-1.25) consuming the highest versus
      the lowest category of GI intake. Evidence of heterogeneity hindered analyses of
      GL and premenopausal risk, although most studies did not observe any significant
      association. Pooled cohort study results indicated no association between
      postmenopausal risk and GL intake (RR 1.03, 95% CI 0.94-1.12). Our findings do
      not provide strong support of an association between dietary GI and GL and breast
      cancer risk.

PMID- 18728656
TI  - Role of LKB1 in lung cancer development.
AB  - Three phenotypically related genetic syndromes and their lesions (LKB1, PTEN, and
      TSC1/2) are identified as frequently altered in lung cancer. LKB1, a kinase
      inactivated in 30% of lung cancers, is discussed in this review. Loss of LKB1
      regulation often coincident with KRAS activation allows for unchecked growth and
      the metabolic capacity to accommodate the proliferation.

PMID- 18728657
TI  - Will histone deacetylase inhibitors require combination with other agents to
      fulfil their therapeutic potential?
AB  - Histone deacetylase inhibitors have progressed rapidly from the laboratory to
      clinical testing. This review highlights the promising data for their combination
      with a wide range of established and novel anticancer agents and discusses the
      mechanisms that underpin these interactions.

PMID- 18728658
TI  - Waiting times for systemic cancer therapy in the United Kingdom in 2006.
AB  - This audit was conducted to measure waiting times for systemic cancer therapy
      across the United Kingdom. All patients, aged 16 years or older, commencing their
      first course of systemic therapy between 13 November and 19 November 2006 were
      eligible for inclusion. Data on 936 patients from 81 hospital sources were
      collected. Systemic therapy is largely given in compliance with national waiting
      time targets. In terms of the Joint Council for Clinical Oncology (JCCO) targets,
      84% of patients commence treatment within 21 days and 98% of patients complied
      with the Department of Health target that treatment should follow within 31 days
      of the decision being agreed with the patient. Only 76% complied with the
      Department of Health 62-day target from GP referral to first definitive
      treatment. However, the date of urgent referral by the GP was not submitted for
      most patients in our survey, leaving a sample of only 84 out of 936 patients (9%
      of total) suitable for this analysis. There was only a 3- to 5-day difference
      between the waiting times for systemic therapy for patients categorised as urgent
      compared with routine. Locally agreed definitions had little impact on patients'
      priority for treatment. This audit has established a baseline measurement of
      waiting times for systemic therapy across the United Kingdom. The continuing
      introduction of novel therapies is likely to have a significant effect on the
      service and we recommend that service managers model the likely impact on
      resource requirements. In addition, urgent treatment should be clearly defined as
      that required within 24 h (maximum 48 h) to avoid the risk of clinical
      deterioration, particularly in patients with acute leukaemia, lymphoma or germ
      cell tumour.

PMID- 18728659
TI  - Automated telephone follow-up after breast cancer: an acceptability and
      feasibility pilot study.
AB  - Traditional clinical follow-up after breast cancer is inefficient at detecting
      relapse and is poorly suited to detecting and ameliorating psychological
      problems. There is interest in developing more effective and efficient methods of
      follow-up. We report a prospective cohort study of the acceptability and
      feasibility of remote, automated telephone follow-up after breast cancer. Women
      with a history of breast cancer were approached at their annual follow-up visit.
      For participants, the follow-up questionnaire was administered on paper at
      baseline. In place of a clinic visit following year, the women completed the same
      questionnaire using an automated telephone system. All patients were given
      mammograms. A semi-structured interview was then conducted to assess the
      acceptability. The potential impact on clinic usage was assessed. In all, 110 of
      121 women (91%) agreed to participate. Seventy-five patients (71%) completed
      follow-up using the new automated system 1 year later. Seventy-one of the 75
      patients found the system easy to use. Forty-nine of the 75 (65.33%) liked the
      system and were happy to use it as their sole method of follow-up. A further 12%
      were happy to use it as part of their follow-up. In only 10.66% of participants
      were concerns raised which led to clinic attendance. Automated questionnaire
      based telephone follow-up is acceptable to women and has the potential to reduce
      attendance at clinic. Further studies to validate this method further are
      planned.

PMID- 18728660
TI  - Q-TWiST analysis of lapatinib combined with capecitabine for the treatment of
      metastatic breast cancer.
AB  - The addition of lapatinib (Tykerb/Tyverb) to capecitabine (Xeloda) delays disease
      progression more effectively than capecitabine monotherapy in women with
      previously treated HER2+ metastatic breast cancer (MBC). The quality-adjusted
      time without symptoms of disease or toxicity of treatment (Q-TWiST) method was
      used to compare treatments. The area under survival curves was partitioned into
      health states: toxicity (TOX), time without symptoms of disease progression or
      toxicity (TWiST), and relapse period until death or end of follow-up (REL).
      Average times spent in each state, weighted by utility, were derived and
      comparisons of Q-TWiST between groups performed with varying combinations of the
      utility weights. Utility weights of 0.5 for both TOX and REL, that is, counting 2
      days of TOX or REL as 1 day of TWiST, resulted in a 7-week difference in quality
      adjusted survival favouring combination therapy (P=0.0013). The Q-TWiST
      difference is clinically meaningful and was statistically significant across an
      entire matrix of possible utility weights. Results were robust in sensitivity
      analyses. An analysis with utilities based on EQ-5D scores was consistent with
      the above findings. Combination therapy of lapatinib with capecitabine resulted
      in greater quality-adjusted survival than capecitabine monotherapy in trastuzumab
      refractory MBC patients.

PMID- 18728661
TI  - Liver-only metastatic colorectal cancer patients and thymidylate synthase
      polymorphisms for predicting response to 5-fluorouracil-based chemotherapy.
AB  - We investigated the association between thymidylate synthase (TS) germline
      polymorphisms and response to 5-fluorouracil-based chemotherapy in 80 patients
      with liver-only metastatic colorectal cancer (MCRC). The tandem repeat
      polymorphism (VNTR) in TS 5'-untranslated region (5'-UTR), which consists of two
      (2R) or three (3R) 28-bp repeated sequences, with or without a G/C nucleotide
      change in 3R carriers (3G or 3C) and a 6-bp insertion/deletion (6+/6-) in the TS
      3'-UTR, was studied. The distinction between high (2R/3G, 3C/3G and 3G/3G) and
      low (2R/2R, 2R/3C and 3C/3C) TS expression genotypes according to the 5'-UTR
      VNTR+G/C nucleotide change showed significant association with tumour response
      (P=0.01). In particular, high TS expression genotypes were found in 8 out of 34
      patients (23.5%) with complete or partial response and in 24 out of 46 patients
      (52%) with stable disease and disease progression. Liver-only MCRC patients are a
      homogeneous and clinical relevant subgroup that may represent an ideal setting
      for studying the actual influence of TS polymorphisms.

PMID- 18728662
TI  - A phase II study of UFT with leucovorin administered as a twice daily schedule in
      the treatment of patients with metastatic colorectal cancer.
AB  - Prolonged infusions have been shown to be safer and potentially more effective
      than bolus regimens of 5-fluorouracil (5-FU) as treatment for metastatic
      colorectal cancer (mCRC). However, infusional 5-FU requires central venous access
      and costly infusion pumps. Oral fluoropyrimidines enable longer exposures to 5-FU
      with increased convenience. Tegafur-uracil (UFT) with leucovorin (LV) given
      thrice daily has improved safety plus comparable survival and response rates to
      bolus 5-FU/LV. We conducted a phase II clinical study in 98 patients with mCRC to
      evaluate if UFT with LV given twice daily provided comparable time to progression
      (TTP), efficacy and tolerability to that reported for thrice daily in two phase
      III clinical studies. Secondary objectives included overall response rate (ORR)
      and overall survival (OS). Median TTP was 3.8 months, when compared with 3.5
      months for thrice daily. The ORR (11%) and median OS (12.8 months) with twice
      daily administration were similar to that of thrice daily administration (12% and
      12.4 months). The incidence of grade 3/4 treatment-related diarrhoea was 30% on
      the twice daily and 21% on the thrice daily schedule. These results suggest that
      twice daily administration has similar efficacy and tolerability to thrice daily
      administration and is an acceptable alternative for patients who would benefit
      from UFT with LV therapy.

PMID- 18728663
TI  - Poorer outcome in stromal HIF-2 alpha- and CA9-positive colorectal
      adenocarcinomas is associated with wild-type TP53 but not with BNIP3 promoter
      hypermethylation or apoptosis.
AB  - Stromal expression of hypoxia inducible factor 2 alpha (HIF-2 alpha) and carbonic
      anhydrase 9 (CA9) are associated with a poorer prognosis in colorectal cancer
      (CRC). Tumour cell death, regulated by a hypoxic stromal microenvironment, could
      be of importance in this respect. Therefore, we correlated apoptosis, TP53
      mutational status and BNIP3 promoter hypermethylation of CRC cells with HIF-2
      alpha- and CA9-related poor outcome. In a series of 195 CRCs, TP53 mutations in
      exons 5-8 were analysed by direct sequencing, and promoter hypermethylation of
      BNIP3 was determined by methylation-specific PCR. Expressions of HIF-2 alpha,
      CA9, p53, BNIP3 and M30 were analysed immunohistochemically. Poorer survival of
      HIF-2 alpha and CA9 stromal-positive CRCs was associated with wild-type TP53
      (P=0.001 and P=0.0391), but not with BNIP3 methylation. Furthermore, apoptotic
      levels were independent of the TP53 status, but lower in unmethylated BNIP3 CRCs
      (P=0.004). It appears that wild-type TP53 in CRC cells favours the progression of
      tumours expressing markers for hypoxia in their stroma, rather than in the
      epithelial compartment. Preserved BNIP3 function in CRC cells lowers apoptosis,
      and may thus be involved in alternative cell death pathways, such as autophagic
      cell death. However, BNIP3 silencing in tumour cells does not impact on hypoxia
      driven poorer prognosis. These results suggest that the biology of CRC cells can
      be modified by alterations in the tumour microenvironment under conditions of
      tumour hypoxia.

PMID- 18728664
TI  - Phase II trial of imatinib mesylate in patients with metastatic melanoma.
AB  - Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs)
      that are considered to be targets for imatinib. We conducted a phase II trial of
      imatinib in patients with metastatic melanoma expressing at least one of these
      PTKs. Twenty-one patients whose tumours expressed at least one PTK (c-kit,
      platelet-derived growth factor receptors, c-abl, or abl-related gene) were
      treated with 400 mg of imatinib twice daily. One patient with metastatic acral
      lentiginous melanoma, containing the highest c-kit expression among all patients,
      had dramatic improvement on positron emission tomographic scan at 6 weeks and had
      a partial response lasting 12.8 months. The responder had a substantial increase
      in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was
      fairly well tolerated: no patient required treatment discontinuation because of
      toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred
      in more than 10% of the patients. Imatinib at the studied dose had minimal
      clinical efficacy as a single-agent therapy for metastatic melanoma. However,
      based on the characteristics of the responding tumour in our study, clinical
      activity of imatinib, specifically in patients with melanoma with certain c-kit
      aberrations, should be examined.

PMID- 18728665
TI  - Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly
      effective against breast cancer metastases.
AB  - New therapies are needed that target breast cancer metastases. In previous
      studies, we have shown that vaccination with pcDNA3.1-Mage-b DNA vaccine is
      effective against breast cancer metastases. In the study presented here, we have
      further enhanced the efficacy of Mage-b vaccination through the improved delivery
      of the vaccine using recombinant Listeria monocytogenes (LM). Three overlapping
      fragments of Mage-b as well as the complete protein-encoding region of Mage-b
      have been expressed as a fusion protein with a truncated non-cytolytic form of
      listeriolysin O (LLO) in recombinant LM. These different Mage-b vaccine strains
      were preventively tested for their efficacy against breast cancer metastases in a
      syngeneic mouse tumour model 4T1. The LM-LLO-Mage-b/2nd, expressing position 311
      660 of the cDNA of Mage-b, was the most effective vaccine strain against
      metastases in the 4T1 mouse breast tumour model. Vaccination with LM-LLO-Mage
      b/2nd dramatically reduced the number of metastases by 96% compared with the
      saline group and by 88% compared with the vector control group (LM-LLO), and this
      correlated with strong Mage-b-specific CD8 T-cell responses in the spleen, after
      restimulation with Mage-b. However, no effect of LM-LLO-Mage-b/2nd was observed
      on 4T1 primary tumours, which may be the result of a complete absence of Mage-b
      specific immune responses in the draining lymph nodes. Vaccination with LM-LLO
      Mage-b/2nd could be an excellent follow-up after removal of the primary tumour,
      to eliminate metastases and residual tumour cells.

PMID- 18728666
TI  - Molecular pathways involved in the synergistic interaction of the PKC beta
      inhibitor enzastaurin with the antifolate pemetrexed in non-small cell lung
      cancer cells.
AB  - Conventional regimens have limited impact against non-small cell lung cancer
      (NSCLC). Current research is focusing on multiple pathways as potential targets,
      and this study investigated molecular mechanisms underlying the combination of
      the PKC beta inhibitor enzastaurin with the multitargeted antifolate pemetrexed
      in the NSCLC cells SW1573 and A549. Pharmacologic interaction was studied using
      the combination-index method, while cell cycle, apoptosis induction, VEGF
      secretion and ERK1/2 and Akt phosphorylation were studied by flow cytometry and
      ELISAs. Reverse transcription-PCR, western blot and activity assays were
      performed to assess whether enzastaurin influenced thymidylate synthase (TS) and
      the expression of multiple targets involved in cancer signaling and cell cycle
      distribution. Enzastaurin-pemetrexed combination was highly synergistic and
      significantly increased apoptosis. Enzastaurin reduced both phosphoCdc25C,
      resulting in G2/M checkpoint abrogation and apoptosis induction in pemetrexed
      damaged cells, and GSK3 beta and Akt phosphorylation, which was additionally
      reduced by drug combination (-58% in A549). Enzastaurin also significantly
      reduced pemetrexed-induced upregulation of TS expression, possibly through E2F-1
      reduction, whereas the combination decreased TS in situ activity (>50% in both
      cell lines) and VEGF secretion. The effects of enzastaurin on signaling pathways
      involved in cell cycle control, apoptosis and angiogenesis, as well as on the
      expression of genes involved in pemetrexed activity provide a strong experimental
      basis to their evaluation as pharmacodynamic markers in clinical trials of
      enzastaurin-pemetrexed combination in NSCLC patients.

PMID- 18728667
TI  - Ex vivo chemosensitivity testing and gene expression profiling predict response
      towards adjuvant gemcitabine treatment in pancreatic cancer.
AB  - Efficacy of chemotherapy for pancreatic cancer may be improved by tailoring it to
      individual chemosensitivity profiles. Identification of nonresponders before
      initiation of treatment may help to avoid side effects. In this study, primary
      pancreatic cancer cells were isolated from 18 patients undergoing
      pancreaticoduodenectomy for pancreatic cancer. Eight commonly used pancreatic
      cancer cell lines were used as controls. Ex vivo chemosensitivity for
      gemcitabine, 5-fluorouracil, mitomycin-C, cisplatinum, oxaliplatinum, paclitaxel
      and a combination of gemcitabine with oxaliplatinum or mitomycin-C was determined
      using a cellular ATP-based tumour chemosensitivity assay (ATP-TCA). Quantitative
      real-time-polymerase chain reaction was performed to determine RNA expression
      levels of genes implicated in chemoresistance. Chemosensitivity towards cytotoxic
      agents was highly variable in primary pancreatic cancer cells and pancreatic
      cancer cell lines. ATP-TCA results for gemcitabine correlated to the tissue
      expression of human equilibrative nucleoside transporter-1 (hENT1). Time to
      relapse in patients with gemcitabine-sensitive tumours was significantly higher
      than in patients with chemoresistant pancreatic cancers (P=0.01; 71 vs 269 days).
      Furthermore, time to relapse in gemcitabine-treated patients was related to hENT1
      expression (P=0.0067). Thus, chemosensitivity testing using ATP-TCA in pancreatic
      cancer is feasible and correlated with time to relapse in gemcitabine-treated
      patients. This suggests that ATP-TCA testing could be used as a decision-making
      tool in the adjuvant treatment of pancreatic cancer.

PMID- 18728668
TI  - Squalene epoxidase, located on chromosome 8q24.1, is upregulated in 8q+ breast
      cancer and indicates poor clinical outcome in stage I and II disease.
AB  - Gains of chromosomes 7p and 8q are associated with poor prognosis among oestrogen
      receptor-positive (ER+) stage I/II breast cancer. To identify transcriptional
      changes associated with this breast cancer subtype, we applied suppression
      subtractive hybridisation method to analyse differentially expressed genes among
      six breast tumours with and without chromosomal 7p and 8q gains. Identified mRNAs
      were validated by real-time RT-PCR in tissue samples obtained from 186 patients
      with stage I/II breast cancer. Advanced statistical methods were applied to
      identify associations of mRNA expression with distant metastasis-free survival
      (DMFS). mRNA expression of the key enzyme of cholesterol biosynthesis, squalene
      epoxidase (SQLE, chromosomal location 8q24.1), was associated with ER+ 7p+/8q+
      breast cancer. Distant metastasis-free survival in stage I/II breast cancer cases
      was significantly inversely related to SQLE mRNA in multivariate Cox analysis
      (P<0.001) in two independent patient cohorts of 160 patients each. The clinically
      favourable group associated with a low SQLE mRNA expression could be further
      divided by mRNA expression levels of the oestrogen-regulated zinc transporter LIV
      1. The data strongly support that SQLE mRNA expression might indicate high-risk
      ER+ stage I/II breast cancers. Further studies on tumour tissue from standardised
      treated patients, for example with tamoxifen, may validate the role of SQLE as a
      novel diagnostic parameter for ER+ early stage breast cancers.

PMID- 18728669
TI  - Association of early life factors and brain tumour risk in a cohort study.
AB  - Using population-based linked birth and cancer registry data, we investigated
      whether the risk of brain tumour in childhood (n=155) was associated with
      perinatal risk factors. This population-based cohort showed that being born into
      a larger family or to a mother with a history of miscarriage may increase
      childhood brain tumour risk.

PMID- 18728670
TI  - A record-linkage study of the development of hepatocellular carcinoma in persons
      with hepatitis C infection in Scotland.
AB  - We investigated trends in first-time hospital admissions and deaths attributable
      to hepatocellular carcinoma (HCC) in a large population-based cohort of 22 073
      individuals diagnosed with hepatitis C viral (HCV) infection through laboratory
      testing in Scotland in 1991-2006. We identified new cases of HCC through record
      linkage to the national inpatient hospital discharge database and deaths
      registry. A total of 172 persons diagnosed with HCV were admitted to hospital or
      died with first-time mention of HCC. Hepatocellular carcinoma incidence increased
      between 1996 and 2006 (average annual change of 6.1, 95% confidence interval
      (CI): 0.9-11.6%, P=0.021). The adjusted relative risk of HCC was greater for
      males (hazard ratio=2.7, 95% CI: 1.7-4.2), for those aged 60 years or older
      (hazard ratio=2.7, 95% CI: 1.9-4.1) compared with 50-59 years, and for those with
      a previous alcohol-related hospital admission (hazard ratio=2.5, 95% CI: 1.7
      3.7). The risk of individuals diagnosed with HCV developing HCC was greatly
      increased compared with the general Scottish population (standardised incidence
      ratio=127, 95% CI: 102-156). Owing to the advancing age of the Scottish HCV
      diagnosed population, the annual number of HCC cases is projected to increase,
      with a consequent increasing burden on the public healthcare system.

PMID- 18728671
TI  - Body size and the risk of biliary tract cancer: a population-based study in
      China.
AB  - Though obesity is an established risk factor for gall bladder cancer, its role in
      cancers of the extrahepatic bile ducts and ampulla of Vater is less clear, as
      also is the role of abdominal obesity. In a population-based case-control study
      of biliary tract cancer in Shanghai, China, odds ratios (ORs) and 95% confidence
      intervals (CIs) were calculated for biliary tract cancer in relation to
      anthropometric measures, including body mass index (BMI) at various ages and
      waist-to-hip ratio (WHR), adjusting for age, sex, and education. The study
      included 627 patients with biliary tract cancer (368 gall bladder, 191 bile duct,
      68 ampulla of Vater) and 959 healthy subjects randomly selected from the
      population. A higher BMI at all ages, including early adulthood (ages 20-29
      years), and a greater WHR were associated with an increased risk of gall bladder
      cancer. A high usual adult BMI (>or=25) was associated with a 1.6-fold risk of
      gall bladder cancer (95% CI 1.2-2.1, P for trend <0.001). Among subjects without
      gallstones, BMI was also positively associated with gall bladder cancer risk.
      Regardless of BMI levels, increasing WHR was associated with an excess risk of
      gall bladder cancer risk, with those having a high BMI (>or=25) and a high WHR
      (>0.90) having the highest risk of gall bladder cancer (OR=12.6, 95% CI 4.8
      33.2), relative to those with a low BMI and WHR. We found no clear risk patterns
      for cancers of the bile duct and ampulla of Vater. These results suggest that
      both overall and abdominal obesity, including obesity in early adulthood, are
      associated with an increased risk of gall bladder cancer. The increasing
      prevalence of obesity and cholesterol stones in Shanghai seems at least partly
      responsible for the rising incidence of gall bladder cancer in Shanghai.

PMID- 18728672
TI  - Occupational exposure to asbestos and mortality among asbestos removal workers: a
      Poisson regression analysis.
AB  - The asbestos industry has shifted from manufacture to stripping/removal work. The
      aim of this study was to investigate early indications of mortality among removal
      workers. The study population consisted of 31 302 stripping/removal workers in
      the Great Britain Asbestos Survey, followed up to December 2005. Relative risks
      (RR) for causes of death with elevated standardised mortality ratios (SMR) and
      sufficient deaths were obtained from Poisson regression. Risk factors considered
      included dust suppression technique, type of respirator used, hours spent
      stripping, smoking status and exposure length. Deaths were elevated for all
      causes (SMR 123, 95% CI 119-127, n=985), all cancers including lung cancer,
      mesothelioma, and circulatory disease. There were no significant differences
      between suppression techniques and respirator types. Spending more than 40 h per
      week stripping rather than less than 10, increased mortality risk from all causes
      (RR 1.4, 95% CI 1.2-1.7), circulatory disease and ischaemic heart disease.
      Elevated mesothelioma risks were observed for those first exposed at young ages
      or exposed for more than 30 years. This study is a first step in assessing long
      term mortality of asbestos removal workers in relation to working practices and
      asbestos exposure. Further follow-up will allow the impact of recent regulations
      to be assessed.

PMID- 18728673
TI  - Survival from cancer in teenagers and young adults in England, 1979-2003.
AB  - Cancer is the leading cause of disease-related death in teenagers and young
      adults aged 13-24 years (TYAs) in England. We have analysed national 5-year
      relative survival among more than 30,000 incident cancer cases in TYAs. For
      cancer overall, 5-year survival improved from 63% in 1979-84 to 74% during 1996
      2001 (P<0.001). However, there were no sustained improvements in survival over
      time among high-grade brain tumours and bone and soft tissue sarcomas. Survival
      patterns varied by age group (13-16, 17-20, 21-24 years), sex and diagnosis.
      Survival from leukaemia and brain tumours was better in the youngest age group
      but in the oldest from germ-cell tumours (GCTs). For lymphomas, bone and soft
      tissue sarcomas, melanoma and carcinomas, survival was not significantly
      associated with age. Females had a better survival than males except for GCTs.
      Most groups showed no association between survival and socioeconomic deprivation,
      but for leukaemias, head and neck carcinoma and colorectal carcinoma, survival
      was significantly poorer with increasing deprivation. These results will aid the
      development of national specialised service provision for this age group and
      identify areas of clinical need that present the greatest challenges.

PMID- 18728674
TI  - Analysis of oncogenic AKT1 p.E17K mutation in carcinomas of the biliary tract and
      liver.

PMID- 18728677
TI  - A functional magnetic resonance imaging technique based on nulling extravascular
      gray matter signal.
AB  - A new functional magnetic resonance imaging (fMRI) technique is proposed based on
      nulling the extravascular gray matter (GM) signal, using a spatially nonselective
      inversion pulse. The remaining MR signal provides cerebral blood volume (CBV)
      information from brain activation. A theoretical framework is provided to
      characterize the sources of GM-nulled (GMN) fMRI signal, effects of partial
      voluming of cerebrospinal fluid (CSF) and white matter, and behaviors of GMN fMRI
      signal during brain activation. Visual stimulation paradigm was used to explore
      the GMN fMRI signal behavior in the human brain at 3T. It is shown that the GMN
      fMRI signal increases by 7.2%+/-1.5%, which is two to three times more than that
      obtained with vascular space occupancy (VASO)-dependent fMRI (-3.2%+/-0.2%) or
      blood oxygenation level-dependent (BOLD) fMRI (2.9%+/-0.7%), using a TR of 3,000
      ms and a resolution of 2 x 2 x 5 mm(3). Under these conditions the fMRI signal-to
      noise ratio (SNR(fMRI)) for BOLD, GMN, and VASO images was 4.97+/-0.76, 4.56+/
      0.86, and 2.43+/-1.06, respectively. Our study shows that both signal intensity
      and activation volume in GMN fMRI depend on spatial resolution because of partial
      voluming from CSF. It is shown that GMN fMRI is a convenient tool to assess CBV
      changes associated with brain activation.

PMID- 18728675
TI  - In vitro and in vivo anticancer efficacy of unconjugated humanized anti-CEA
      monoclonal antibodies.

PMID- 18728678
TI  - Tumor necrosis factor receptor-1 is essential for LPS-induced sensitization and
      tolerance to oxygen-glucose deprivation in murine neonatal organotypic
      hippocampal slices.
AB  - Inflammation and ischemia have a synergistic damaging effect in the immature
      brain. The role of tumor necrosis factor (TNF) receptors 1 and 2 in
      lipopolysaccharide (LPS)-induced sensitization and tolerance to oxygen-glucose
      deprivation (OGD) was evaluated in neonatal murine hippocampal organotypic
      slices. Hippocampal slices from balb/c, C57BL/6 TNFR1(-/-), TNFR2(-/-), and wild
      type (WT) mice obtained at P6 were grown in vitro for 9 days. Preexposure to LPS
      immediately before OGD increased propidium iodide-determined cell death in
      regions CA1, CA3, and dentate gyrus from 4 up to 48 h after OGD (P<0.001).
      Extending the time interval between LPS exposure and OGD to 72 h resulted in
      tolerance, that is reduced neuronal cell death after OGD (P<0.05). Slices from
      TNFR1(-/-) mice showed neither LPS-induced sensitization nor LPS-induced
      tolerance to OGD, whereas both effects were present in slices from TNFR2(-/-) and
      WT mice. Cytokine secretion (TNFalpha and interleukin-6) during LPS exposure was
      decreased in TNFR1(-/-) slices and increased in TNFR2(-/-) as compared with WT
      slices. We conclude that LPS induces sensitization or tolerance to OGD depending
      on the time interval between exposure to LPS and OGD in murine hippocampal slice
      cultures. Both paradigms are dependent on signaling through TNFR1.

PMID- 18728679
TI  - The role of animal models in evaluating reasonable safety and efficacy for human
      trials of cell-based interventions for neurologic conditions.
AB  - Progress in regenerative medicine seems likely to produce new treatments for
      neurologic conditions that use human cells as therapeutic agents; at least one
      trial for such an intervention is already under way. The development of cell
      based interventions for neurologic conditions (CBI-NCs) will likely include
      preclinical studies using animals as models for humans with conditions of
      interest. This paper explores predictive validity challenges and the proper role
      for animal models in developing CBI-NCs. In spite of limitations, animal models
      are and will remain an essential tool for gathering data in advance of first-in
      human clinical trials. The goal of this paper is to provide a realistic lens for
      viewing the role of animal models in the context of CBI-NCs and to provide
      recommendations for moving forward through this challenging terrain.

PMID- 18728680
TI  - C3a receptor antagonist attenuates brain injury after intracerebral hemorrhage.
AB  - Neuroprotective therapy targeting the complement cascade may reduce injury
      associated with intracerebral hemorrhage (ICH). We investigated the role of C3a
      receptor antagonist (C3aRA) after ICH in mice. Autologous whole blood was infused
      into the right striatum of mice that were treated with C3aRA or vehicle, using
      both a pre- and postinjury dosing regimen. Hematoma volume, brain water content,
      and inflammatory cell profile were assessed at 72 h post-ICH. Neurologic
      dysfunction was assessed by evaluating both spatial memory and sensorimotor
      capacity. Animals pretreated with C3aRA showed significantly improved neurologic
      function, brain water content, and granulocyte infiltration relative to vehicle
      treated animals when assessed at 72 h. There was no significant difference in
      hemorrhagic/nonhemorrhagic ratio of microglial activation among all groups.
      Hematoma volumes were also not significantly different between C3aRA-treated and
      vehicle-treated animals. Administration of C3aRA beginning 6 h postinjury
      afforded significant amelioration of neurologic dysfunction as well as a
      reduction in brain water content. Treatment with C3aRA improved neurologic
      outcome while reducing inflammatory cell infiltration and brain edema formation
      after experimental ICH in mice. Results of this study suggest that the C3a
      receptor may be a promising target for therapeutic intervention in hemorrhagic
      stroke.

PMID- 18728681
TI  - Neuregulin-1 signaling in brain endothelial cells.
AB  - Neuregulin-1 (NRG1) signaling has multiple functions in neurons and glia. The
      data in this study show that NRG1 may also possess significant signaling and
      cytoprotective properties in human brain microvascular endothelial cells (BMECs).
      Neuregulin-1 mRNA and protein expression are present in these cells, and NRG1
      receptors erbB2 and erbB3 are phosphorylated in response to NRG1. Neuregulin-1
      triggers clear biologic responses in BMECs--elevated phospho-Akt levels,
      increased ring formation in a Matrigel assay, and decreased cell death after
      oxidative injury with H(2)O(2). These data suggest that NRG1 signaling is
      functional and cytoprotective in BMECs.

PMID- 18728691
TI  - A wiki for the life sciences where authorship matters.
AB  - WikiGenes is the first wiki system to combine the collaborative and largely
      altruistic possibilities of wikis with explicit authorship. In view of the
      extraordinary success of Wikipedia there remains no doubt about the potential of
      collaborative publishing, yet its adoption in science has been limited. Here I
      discuss a dynamic collaborative knowledge base for the life sciences that
      provides authors with due credit and that can evolve via continual revision and
      traditional peer review into a rigorous scientific tool.

PMID- 18728693
TI  - The DLX1and DLX2 genes and susceptibility to autism spectrum disorders.
AB  - An imbalance between excitation and inhibition in the cerebral cortex has been
      suggested as a possible etiology of autism. The DLX genes encode homeodomain
      containing transcription factors controlling the generation of GABAergic cortical
      interneurons. The DLX1 and DLX2 genes lie head-to-head in 2q32, a region
      associated with autism susceptibility. We investigated 6 Tag SNPs within the
      DLX1/2 genes in two cohorts of multiplex (MPX) and one of simplex (SPX) families
      for association with autism. Family-based association tests showed strong
      association with five of the SNPs. The common alleles of rs743605 and rs4519482
      were significantly associated with autism (P<0.012) in the first sample of 138
      MPX families, with the latter remaining significant after correction for multiple
      testing (P(cor)=0.0046). Findings in a second sample of 169 MPX families not only
      confirmed the association at rs4519482 (P=0.034) but also showed strong allelic
      association of the common alleles at rs788172, rs788173 and rs813720
      (P(cor)=0.0003-0.04). In the combined MPX families, the common alleles were all
      significantly associated with autism (P(cor)=0.0005-0.016). The GGGTG haplotype
      was over transmitted in the two MPX cohorts and the combined samples
      [P(cor)<0.05: P(cor)=0.00007 for the combined MPX families, Odds Ratio: 1.75 (95%
      CI: 1.33-2.30)]. Further testing in 306 SPX families replicated the association
      at rs4519482 (P=0.033) and the over transmission of the haplotype GGGTG (P=0.012)
      although P-values were not significant after correction for multiple testing. The
      findings support the presence of two functional polymorphisms, one in or near
      each of the DLX genes that increase susceptibility to, or cause, autism in MPX
      families where there is a greater genetic component for these conditions.

PMID- 18728694
TI  - Intra- and inter-individual variability in location data for two U.S. health
      compromised elderly cohorts.
AB  - This study provides descriptive statistical data on daily time spent in three
      locations of exposure assessment interest for two panel studies of health
      compromised elderly individuals >65-year-old having multiple days of human
      activity data. The panel studies include individuals living in Los Angeles (CA)
      and Baltimore (MD) in various housing types. Three general locations are
      evaluated: outdoors, in vehicles, and total indoors. Of particular interest is
      providing information regarding the within- and between-individual variability in
      the time use data for the three locations. The data are analyzed using non
      parametric statistics and alternative statistical models. Within and between
      variability are evaluated using intraclass correlation coefficients (ICCs); daily
      "lag-one" autocorrelation coefficients are also provided for the two samples.
      There were significant gender differences for selected seasonal and/or day-of-the
      week metrics for: (1) outdoor time in Los Angeles, but not in Baltimore, and (2)
      in-vehicle time in both areas. Elderly women spent more time in these locations
      than similarly aged men. The ICC statistic indicates that most of the variability
      in the time spent in the three locations is due to intraindividual variability
      rather than to inter-individual variability. The results indicate that US
      Environmental Protection Agency should consider gender, day-of-the-week, and time
      of-day data in its exposure modeling of daily activities undertaken by the health
      compromised elderly population.

PMID- 18728695
TI  - Hazardous chemicals in synthetic turf materials and their bioaccessibility in
      digestive fluids.
AB  - Many synthetic turf fields consist of not only artificial grass but also rubber
      granules that are used as infill. The public concerns about toxic chemicals
      possibly contained in either artificial (polyethylene) grass fibers or rubber
      granules have been escalating but are based on very limited information available
      to date. The aim of this research was to obtain data that will help assess
      potential health risks associated with chemical exposure. In this small-scale
      study, we collected seven samples of rubber granules and one sample of artificial
      grass fiber from synthetic turf fields at different ages of the fields. We
      analyzed these samples to determine the contents (maximum concentrations) of
      polycyclic aromatic hydrocarbons (PAHs) and several metals (Zn, Cr, As, Cd, and
      Pb). We also analyzed these samples to determine their bioaccessible fractions of
      PAHs and metals in synthetic digestive fluids including saliva, gastric fluid,
      and intestinal fluid through a laboratory simulation technique. Our findings
      include: (1) rubber granules often, especially when the synthetic turf fields
      were newer, contained PAHs at levels above health-based soil standards. The
      levels of PAHs generally appear to decline as the field ages. However, the decay
      trend may be complicated by adding new rubber granules to compensate for the loss
      of the material. (2) PAHs contained in rubber granules had zero or near-zero
      bioaccessibility in the synthetic digestive fluids. (3) The zinc contents were
      found to far exceed the soil limit. (4) Except one sample with a moderate lead
      content of 53 p.p.m., the other samples had relatively low concentrations of lead
      (3.12-5.76 p.p.m.), according to soil standards. However, 24.7-44.2% of the lead
      in the rubber granules was bioaccessible in the synthetic gastric fluid. (5) The
      artificial grass fiber sample showed a chromium content of 3.93 p.p.m., and 34.6%
      and 54.0% bioaccessibility of lead in the synthetic gastric and intestinal
      fluids, respectively.

PMID- 18728697
TI  - Tandem Intramolecular Benzyne-Furan Cycloadditions. Total Synthesis of
      Vineomycinone B(2) Methyl Ester.
AB  - We have exploited tandem intramolecular benzyne-furan cycloadditions employing
      three different benzyne precursors to generate substituted
      bisoxabenzonorbornadienes in a single operation. The regiochemical outcomes in
      these Diels-Alder reactions were effectively controlled by using disposable
      silicon tethers to link the reacting benzynes and furan moieties. Two different
      methods for converting the intermediate bisoxabenzonorbornadienes to substituted
      anthrarufins were developed. The first tactic entails the initial cleavage of the
      silicon tethers followed by regioselective ring opening of the
      oxabicycloheptadienes and oxidation of the central ring giving the target
      anthrarufin, whereas the second features the regioselective ring opening of the
      oxabicycloheptadienes followed by protiodesilylation and oxidation. When the
      starting furans bear carbohydrate substitutents, this new methodology enables the
      rapid assembly of the glycosyl-substituted aromatic cores of complex C-aryl
      glycoside antibiotics from simple starting materials. The utility of this novel
      approach to anthrarufins and C-aryl glycosides is exemplified in a triply
      convergent synthesis of vineomycinone B(2) methyl ester.

PMID- 18728696
TI  - Synthesis and biological evaluation of (-)-dictyostatin and stereoisomers.
AB  - Total syntheses of (-)-dictyostatin, 6,16-bis-epi-dictyostatin, 6,14,19-tris-epi
      dictyostatin and a number of other isomers and analogs are reported. Three main
      fragments-top, middle and bottom-were first assembled and then joined by
      olefination or anionic addition reactions. After appending the two dienes at
      either end of the molecule, macrolactonization and deprotection completed the
      syntheses. The work proves both the relative and absolute configurations of (-)
      dictyostatin. The compounds were evaluated by cell-based measurements of
      increased microtubule mass and antiproliferative activity, and in vitro tubulin
      polymerization assays as well as competitive assays with paclitaxel for its
      binding site on microtubules. These assays showed dictyostatin to be the most
      potent of the agents and further showed that the structural alterations caused
      from 20- to >1000-fold decreases in activity.

PMID- 18728699
TI  - Trabectedin and its potential in the treatment of soft tissue sarcoma.
AB  - Trabectedin is a new marine-derived compound that binds the DNA minor groove and
      interacts with proteins of the DNA repair machinery. Phase I trials have
      established the standard regimen as 1500 mug/m(2) 24-hour continuous infusion
      repeated every 3 weeks. Several phase II trials have shown response in 5%-10% of
      unselected patients with soft tissue sarcoma failing prior chemotherapy and
      disease stabilisation in 30%-40%. Furthermore, prolonged disease control has been
      described in 15%-20% of patients. Toxicities are mainly haematological and
      hepatic with grade 3-4 neutropenia and thrombocytopenia observed in approximately
      50% and 20% of patients respectively, and grade 3-4 elevation of liver enzymes
      observed in 35%-50% of patients treated with trabectedin. Current research
      focuses on the identification of predictive factors for patients with soft tissue
      sarcoma treated with trabectedin.

PMID- 18728698
TI  - Review of photodynamic therapy in actinic keratosis and basal cell carcinoma.
AB  - The number of non-melanoma skin cancers is increasing worldwide, and so also the
      demand for effective treatment modalities. Topical photodynamic therapy (PDT)
      using aminolaevulinic acid or its methyl ester has recently become good treatment
      options for actinic keratosis and basal cell carcinoma; especielly when treating
      large areas and areas with field cancerization. The cure rates are usually good,
      and the cosmetic outcomes excellent. The only major side effect reported is the
      pain experienced by the patients during treatment. This review covers the
      fundamental aspects of topical PDT and its application for treatment of actinic
      keratosis and basal cell carcinoma. Both potentials and limitations will be
      reviewed, as well as some recent development within the field.

PMID- 18728700
TI  - Tamsulosin oral controlled absorption system (OCAS) in the treatment of benign
      prostatic hypertrophy.
AB  - The efficacy of tamsulosin at the cost of a relatively benign side effect profile
      has been attributed to receptor selectivity directed at the alpha(1a) and
      alpha(1d) adrenergic receptor subtypes. The oral-controlled absorption system
      (OCAS((R))) represents a drug delivery refinement that incorporates a matrix of
      gel-forming and gel-enhancing agents to promote a constant drug release
      independent of environmental food or fluid. There are clinical data to support
      the concept that drug peaks are lessened and that drug release continues
      throughout the alimentary tract due to the OCAS formulation. Furthermore this
      equates with less adverse effects on physiologic parameters. To date however
      improvements in cardiovascular symptoms such as dizziness, headache and syncope
      have not been demonstrated in healthy men. Ejaculatory dysfunction appears less
      problematic with the OCAS preparation. Tamsulosin OCAS may be of greatest benefit
      to men with cardiovascular co-morbidities taking anti-hypertensive medications
      that might predispose them to symptomatic hypotensive episodes. It will be
      necessary to evaluate this group of men more closely in further trials to
      determine what they stand to gain from changing medications, and then relate this
      to drug costs to draw a final conclusion as to the place of tamsulosin OCAS in
      contemporary urological practice.

PMID- 18728701
TI  - A review of solifenacin in the treatment of urinary incontinence.
AB  - Overactive bladder (OAB) is a prevalent condition which has an adverse effect on
      quality of life. The presence of urgency incontinence confers significant
      morbidity above and beyond that of OAB sufferers who are continent. The primary
      treatment for OAB and urgency incontinence is a combination of behavioral
      measures and antimuscarinic drug therapy. The ideal antimuscarinic agent should
      effectively relieve the symptoms of OAB, with the minimum of side effects; it
      should be available as a once-daily sustained release formulation and in dosage
      strength that allows easy dose titration for the majority of sufferers.
      Solifenacin succinate was launched in 2005, and has been shown in both short and
      long term clinical trials to fulfill these requirements. Solifenacin is a
      competitive M3 receptor antagonist with a long half-life (45-68 hours). It is
      available in two dosage strengths namely a 5 or 10 mg once-daily tablet. The
      efficacy and tolerability of solifenacin for the treatment of all symptoms of OAB
      has been evaluated in a number of large, placebo controlled, randomized trials.
      Long-term safety, efficacy, tolerability and persistence with treatment have been
      established in an open label 40 week continuation study.

PMID- 18728702
TI  - A review of lenalidomide in combination with dexamethasone for the treatment of
      multiple myeloma.
AB  - Lenalidomide (also known as Revlimid((R)), CC-5013) is an immunomodulatory
      derivative of thalidomide and has more potent anti-tumor and anti-inflammatory
      effects than thalidomide. The molecular mechanisms of anti-tumor activity of
      lenalidomide have been extensively studied in multiple myeloma (MM) both
      preclinical models and in clinical trials. Lenalidomide: directly triggers growth
      arrest and/or apoptosis of drug resistant MM cells; inhibits binding of MM cells
      to bone marrow (BM) extracellular matrix proteins and stromal cells; modulates
      cytokine secretion and inhibits angiogenesis in the BM milieu; and augments host
      anti-tumor immunity. Lenalidomide achieved responses in patients with relapsed
      refractory MM. Moreover, lenalidomide with dexamethasone (Dex) demonstrates more
      potent anti-MM activities than Dex both in vitro and in randomized phase III
      clinical trials. Specifically, the combination improved overall and extent of
      response, as well as prolonged time to progression and overall survival,
      resulting in FDA approval of lenalidomide with Dex for therapy MM relapsing after
      prior therapy.

PMID- 18728703
TI  - Contribution of capecitabine for therapy of patients with gastroesophageal
      cancer: an update of recent phase III results.
AB  - BACKGROUND: Capecitabine, an orally administered fluoropyrimidines, is widely
      used in the treatment of multiple malignancies. It has been extensively evaluated
      in patients with gastroesophageal carcinoma. Since recent reviews have discussed
      phase I/II trials (Cancer 107:221-231, 2006; Drugs 67:601-610, 2007), we focus on
      the impact of the results of the most current phase III trials using capectiabine
      in the treatment of advanced gastroesophageal cancers, primarily in the first
      line setting. METHODS: To find published phase III trials, Medline was searched
      for English-language clinical trials published from 1996 through June 2007 along
      with relevant abstracts presented at the American Society of Clinical Oncology,
      and meetings of the European Cancer Conference and European Society of Medical
      Oncology. Only representative trials were chosen for this manuscript. RESULTS:
      The most frequently investigated combinations are capecitabine with taxanes,
      platinols, and camptothecins. Recent results of a large phase III trial (REAL-2)
      in untreated patients with gastroesophageal cancer suggest that capecitabine is a
      non-inferior substitute for intravenous 5-fluorouracil. These results of REAL-2
      trial are substantiated by a smaller phase III trial. Previous analysis of
      multiple trials had suggested that capecitabine, when combined in doses lower
      than 1250 mg/m(2) twice daily, consistently resulted in lower frequency of Grade
      3 or 4 toxic effects. CONCLUSIONS: Capecitabine provides much needed convenience
      to patients with gastroesophageal cancer. The recent data derived from two phase
      III trials confirm that capecitabine is a suitable substitute for intravenous 5
      fluorouracil in patients whose swallowing is not greatly affected. Capecitabine
      remains a subject of further investigations in this group of patients with
      interest.

PMID- 18728704
TI  - Calcipotriol/betamethasone dipropionate in the treatment of psoriasis vulgaris.
AB  - Psoriasis is one of the most common skin diseases. The mainstay of treatment for
      the vast majority of patients is topical therapy. A rising first-line treatment
      modality for psoriasis vulgaris is the two-compound ointment containing
      calcipotriol 50 mug/g plus betamethasone dipropionate 0.5 mg/g (Dovobet((R)),
      Daivobet((R)), Taclonex((R))), which combines a vitamin D analog and a
      corticosteroid. This innovative formulation preserves the activity and
      bioavailability of the two components and many clinical studies have demonstrated
      that it has a greater efficacy, tolerability, and a rapid onset of action
      compared with its individual ingredients or tacalcitol.

PMID- 18728705
TI  - Treatment of gastrointestinal stromal tumor: focus on imatinib mesylate.
AB  - Gastrointestinal stromal tumor (GIST) is a rare primary neoplasm of the
      gastrointestinal tract, mesentery, or omentum. In the past, surgery has been the
      only effective treatment. The diagnosis and treatment of GIST has been
      revolutionized over the past decade, since expression of the receptor tyrosine
      kinase KIT was shown to occur on these tumors. Mutations in this proto-oncogene
      commonly cause constitutive activation of the KIT tyrosine kinase receptor, an
      important factor in the pathogenesis of the disease. The development of specific
      tyrosine kinase inhibitors, such as imatinib mesylate, has led to a breakthrough
      in the treatment of advanced GIST. Treatment with this drug has led to
      significant improvements in survival, with overall response rates in excess of
      80%. Side effects are common, but usually manageable. The success of this drug
      has led to further trials investigating its use in the pre- and postoperative
      situation. This review summarizes the current knowledge of GIST and imatinib
      treatment and possible future developments.

PMID- 18728707
TI  - Long-term safety of aromatase inhibitors in the treatment of breast cancer.
AB  - Following promising data for metastatic breast cancer in terms of efficacy and
      safety profile, third-generation aromatase inhibitors (AI), anastrozole,
      letrozole, and exemestane, underwent a full development in early setting. If
      recent results consistently show the superiority of these agents over tamoxifen,
      the therapeutic strategies of AIs in adjuvant setting are still debated. Beyond
      the choice of clinical strategy, the long duration of exposure to AI in adjuvant
      setting required a full determination of the long-term toxicity profile of these
      agents. While all three AIs have either favorable (decreased incidence of hot
      flashes, gynecologic and thromboembolic side-effects) or unfavorable (skeletal
      complications, arthralgia, musculoskeletal pain, sexual dysfunction) class
      adverse events, some variability between AIs has been reported in side-effects as
      well as gastrointestinal, urogenital, neurologic, and visual disturbances,
      confirming the lack of interchangeability between the three AIs. The overall
      therapeutic index of AIs appears today superior to that of tamoxifen with proven
      improved efficacy and better toxicity profile. This review will explore the
      results from the available adjuvant AIs trials with a particular emphasis on
      safety profiles, quality of life, and therapeutic index, helping to define the
      present role of AIs in the adjuvant management of postmenopausal patients with
      breast cancer.

PMID- 18728706
TI  - Therapeutic options for chronic myeloid leukemia: focus on imatinib (Glivec,
      Gleevectrade mark).
AB  - Treatment options for chronic myeloid leukemia (CML) have changed dramatically
      during the last decades. Interferon-alpha treatment and stem cell transplantation
      (SCT) clearly improved survival over conventional chemotherapy and offered the
      possibility of complete and durable responses. With the advent of the small
      molecule inhibitor imatinib mesylate (Glivec((R)), Gleevectrade mark) targeting
      the causative Bcr-Abl oncoprotein, the era of molecular cancer therapy began with
      remarkable success especially in chronic phase patients. Today, imatinib is the
      first-line treatment for CML. However, imatinib does not appear to be capable to
      eliminate all leukemia cells in the patients and pre-existing as well as acquired
      resistance to the drug has been increasingly recognized. To overcome these
      problems, several strategies involving dose escalation, combinations with other
      agents, and novel Bcr-Abl inhibitors have been developed.

PMID- 18728708
TI  - Critical appraisal of medical devices in the management of cerebrovascular
      disease.
AB  - Medical devices may revolutionize the management of acute ischemic stroke and
      prevention of recurrent events. By comparison with pharmaceuticals, the device
      approval process and subsequent application of these devices in stroke treatment
      is founded on a paucity of Class I evidence-based clinical trial data.
      Thromboembolectomy for acute stroke, stenting of cervical or cerebral arteries
      for stroke prevention, and percutaneous closure of patent foramen ovale for
      prevention or recurrent cerebral ischemia are being done with an ever-increasing
      frequency despite few, if any, randomized clinical trials to confirm the
      appropriateness of the interventions. The current basis, or lack thereof, for
      these interventions for cerebrovascular disease is therefore discussed. As such,
      a critical appraisal of the available clinical data does not support widespread
      use of medical devices at this time outside of well-designed clinical trials.

PMID- 18728710
TI  - A review of topotecan in combination chemotherapy for advanced cervical cancer.
AB  - Treatment of advanced, recurrent or persistent cervical cancer includes
      radiotherapy and chemotherapy. Radiation has been the primary treatment modality
      for locoregionally advanced cervical cancer. Concomitant systemic cisplatin
      chemotherapy and radiation have shown high response rates with improvements in
      durable remissions and overall survival. Cisplatin has been the standard
      medication for the treatment of advanced cervical cancer. Combinations with other
      chemotherapeutic agents have been the subject of clinical trials with varying
      results. The toxicity of combination chemotherapy and tolerability of patients
      are other factors that should be considered in the management of patients with
      advanced disease. Recently topotecan, in combination with cisplatin, achieved
      increased response and overall survival rates without further compromising the
      patients' quality of life. This review focuses on the mechanism of action and
      toxicities of topotecan, as well as its role as a radio-sensitizer and
      chemotherapeutic agent in the management of advanced, recurrent, or persistent
      cervical cancer. Other combination modalities and dosages are also discussed.

PMID- 18728709
TI  - Review of pemetrexed in combination with cisplatin for the treatment of malignant
      pleural mesothelioma.
AB  - Malignant pleural mesothelioma is a resistant form of lung cancer, and its
      incidence continues to rise in Europe and Australia. Until recently, chemotherapy
      had not been shown to be effective in the treatment of this slowly progressive
      disease. In 2004, the combination of pemetrexed and cisplatin was shown to induce
      high response rates in MPM. This article reviews the published literature
      describing the development and testing of this therapeutic combination in
      mesothelioma, and examines in detail the key phase III clinical trial that led to
      the approval of pemetrexed by the US FDA. Ongoing research will further define
      the role of pemetrexed plus cisplatin in the treatment of MPM.

PMID- 18728711
TI  - Therapeutical approach to plasma homocysteine and cardiovascular risk reduction.
AB  - Homocysteine is a sulfur-containing aminoacid produced during metabolism of
      methionine. Since 1969 the relationship between altered homocysteine metabolism
      and both coronary and peripheral atherotrombosis is known; in recent years
      experimental evidences have shown that elevated plasma levels of homocysteine are
      associated with an increased risk of atherosclerosis and cardiovascular ischemic
      events. Several mechanisms by which elevated homocysteine impairs vascular
      function have been proposed, including impairment of endothelial function,
      production of reactive oxygen species (ROS) and consequent oxidation of low
      density lipids. Endothelial function is altered in subjects with
      hyperhomocysteinemia, and endothelial dysfunction is correlated with plasma
      levels of homocysteine. Folic acid and B vitamins, required for remethylation of
      homocysteine to methionine, are the most important dietary determinants of
      homocysteine and daily supplementation typically lowers plasma homocysteine
      levels; it is still unclear whether the decreased plasma levels of homocysteine
      through diet or drugs may be paralleled by a reduction in cardiovascular risk.

PMID- 18728712
TI  - Management of laryngopharyngeal reflux with proton pump inhibitors.
AB  - There is a lack of consistent guidelines and consensus for the diagnosis of
      laryngopharyngeal reflux (LPR). A therapeutic trial with a proton pump inhibitor
      (PPI) has been suggested to identify patients with LPR. This review focuses on
      the current difficulties in diagnosing the disease and examines the evidence for
      the effectiveness of PPI therapy in suspected reflux-related laryngeal symptoms.
      Additionally, mode of action, safety, and tolerability of PPIs are described. A
      total of 7 placebo-controlled trials were identified and included in the review.
      All studies evaluated the effect of a PPI on symptoms and objective laryngoscopic
      findings in suspected LPR. Data from these trials show that PPI therapy is no
      more effective than placebo in producing symptom relief in patients suspected of
      LPR. Symptoms, laryngoscopic findings, or abnormal findings on pH monitoring will
      not predict response to PPI therapy. High placebo response levels suggest a much
      more complex and multifactorial pathophysiology of LPR than simple acid reflux.
      Further studies are needed to characterize subgroups of patients with reflux
      associated laryngeal symptoms that might benefit from treatment with PPI. Future
      studies should use validated patient reported outcome measures with endpoints
      that represent a predefined clinically meaningful change in symptom scores.

PMID- 18728713
TI  - A review of telavancin in the treatment of complicated skin and skin structure
      infections (cSSSI).
AB  - Telavancin is a novel antibiotic being investigated for the treatment of serious
      infections caused by Gram-positive bacteria, including complicated skin and skin
      structure infections (cSSSI) and pneumonia. This once-daily intravenous
      lipoglycopeptide exerts rapid bactericidal activity via a dual mechanism of
      action. It is intended for use to combat infections caused by Staphylococcus
      aureus and other Gram-positive bacteria, including methicillin-resistant and
      vancomycin-intermediate strains of S. aureus (MRSA and VISA, respectively).
      Vancomycin is the current gold standard in treating serious infections caused by
      Gram-positive bacteria, especially MRSA. In recent clinical trials, telavancin
      has shown excellent efficacy in phase II and III multinational, randomized,
      double-blinded studies of cSSSI. In the phase II FAST 2 study, which compared
      telavancin 10 mg/kg intravenously q 24 h vs standard therapy (an
      antistaphylococcal penicillin at 2 g IV q 6 h or vancomycin 1 gm IV q 12 h), the
      clinical success rate in the telavancin-treated group was 96% vs 94% in the
      standard therapy group. In two identical phase III trials comparing telavancin
      versus vancomycin at the doses of the FAST 2 study for cSSSI, the clinical cure
      rates were 88.3% and 87.1%, respectively. Two additional phase III clinical
      trials investigating telavancin for use in hospital-acquired pneumonia, caused by
      Gram-positive bacteria are currently ongoing. Telavancin is currently under
      regulatory review in both the United States and Europe for the indication of
      treatment of cSSSI.

PMID- 18728714
TI  - Cannabinoids in the management of difficult to treat pain.
AB  - This article reviews recent research on cannabinoid analgesia via the
      endocannabinoid system and non-receptor mechanisms, as well as randomized
      clinical trials employing cannabinoids in pain treatment. Tetrahydrocannabinol
      (THC, Marinol((R))) and nabilone (Cesamet((R))) are currently approved in the
      United States and other countries, but not for pain indications. Other synthetic
      cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis
      remains illegal in most jurisdictions but is also under investigation.
      Sativex((R)), a cannabis derived oromucosal spray containing equal proportions of
      THC (partial CB(1) receptor agonist ) and cannabidiol (CBD, a non-euphoriant,
      anti-inflammatory analgesic with CB(1) receptor antagonist and endocannabinoid
      modulating effects) was approved in Canada in 2005 for treatment of central
      neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain.
      Numerous randomized clinical trials have demonstrated safety and efficacy for
      Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and
      cancer pain. An Investigational New Drug application to conduct advanced clinical
      trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid
      analgesics have generally been well tolerated in clinical trials with acceptable
      adverse event profiles. Their adjunctive addition to the pharmacological
      armamentarium for treatment of pain shows great promise.

PMID- 18728715
TI  - Zoledronic acid in the management of metastatic bone disease.
AB  - Many patients with advanced cancer experience decreased bone strength due to
      metastatic foci, underlying osteoporosis and/or cancer treatment induced bone
      loss. The clinical consequences of metastatic disease involving the skeleton are
      widespread. This review focuses on the efficacy, pharmacology, and safety when
      using intravenous biphosphonate such a zoledronic acid for cancer bone
      metastases. Zoledronic acid is the gold standard for the medical management of
      metastatic bone disease. The indications for treatment include prevention of
      skeletal relevant events (SRE), osteoporotic complications, and palliation of
      bone pain, among others. Zoledronic acid is the only bisphosphonate effective in
      decreasing SREs associated with bone metastases from advanced renal cell
      carcinoma and prostate cancer. Regarding prostate cancer, zoledronic acid
      effectively prevents both bone loss in patients with locally advanced disease
      receiving androgen deprivation therapy and SREs in men with hormone-refractory or
      hormone-sensitive metastatic disease. Zoledronic acid has an acceptable safety
      profile and tolerability, and has been effective at significantly decreasing the
      incidence, delaying the onset, and reducing the overall risk of experiencing an
      SRE compared to placebo. It is the only bisphosphonate currently approved for the
      prevention and treatment of skeletal complications in patients with bone
      metastases due to all solid tumors.

PMID- 18728717
TI  - Treating oligohydramnios with extract of Salvia miltiorrhiza: A randomized
      control trial.
AB  - OBJECTIVE: To determine whether purified herbal extract of Salvia miltiorrhiza
      can improve the amniotic fluid volume in pre-term oligohydramnios by improving
      uteroplacental circulation. METHODS: Forty-three pregnant women with
      oligohydramnios received a daily intravenous dose of 30 mL of salvia extract
      mixed with 5% glucose 500 mL. A control group of 41 women received daily 5%
      glucose 500 mL only. The amniotic fluid index (AFI) was assessed at least twice a
      week by ultrasonographists who were blinded to the treatment. Both women and
      fetuses were monitored closely. The change in AFIwas calculated and compared by
      paired t test within and between groups. The revised recommendations for
      improving the quality of reports of parallel group randomized trials were used.
      RESULTS: After a mean of 7.2 +/- 2.7 days' therapy, ranging from 3 to 18 days,
      the AFIincreased significantly from a mean of 4.9 +/- 2.3 cm to a mean of 7.12 +/
      2.36 cm, by a mean of AFI0.18 +/- 0.06 cm/day (paired t = 3.62, p < 0.005). In
      the control group, the AFIincreased from a mean of 5.1 +/- 2.4 cm to a mean of
      5.5 +/- 3.1 cm after a mean of 6.1 +/- 3.3 days' treatment, ranging from 4 to 15
      days. The effect of salvia treatment on AFIin the salvia group was significantly
      greater than in the control group (p < 0.001). No side effects were observed in
      treated patients. CONCLUSION: Salvia miltiorrhiza is an effective Chinese
      medicine for the treatment of oligohydramnios.

PMID- 18728718
TI  - Dalbavancin in the treatment of complicated skin and soft-tissue infections: a
      review.
AB  - Increasing rates of antimicrobial resistance among strains of Streptococcus,
      Staphylococcus, and Enterococcus spp. have been widely documented. At least 50%
      of nosocomial Staphylococcus aureus infections in intensive care units in the US
      and UK are due methicillin-resistant S. aureus (MRSA). Drug resistance is not
      confined to hospitals, and community-acquired MRSA (CA-MRSA) strains are now
      common causes of complicated skin and soft-tissue infections (cSSTIs) in many
      regions. Dalbavancin is a novel parenterally administered semisynthetic
      lipoglycopeptide similar to the naturally produced glycopeptides vancomycin and
      teicoplanin. Dalbavancin features a multifaceted mechanism of action that
      inhibits bacterial cell wall formation by two different mechanisms that enhances
      its activity against a wide range of gram-positive bacteria including
      staphylococci, streptococci, enterococci, and some anaerobes. Additionally,
      dalbavancin possesses unique pharmacokinetic properties, the most significant of
      which is a long terminal half-life that allows for once weekly dosing. This
      attribute may prove to yield clinical and cost benefit. Overall, clinical trials
      indicate that dalbavancin is a safe, well-tolerated, and effective antimicrobial
      agent. In the largest investigation evaluating dalbavancin for the treatment of
      cSSTIs, it appeared to be as effective as linezolid. Dalbavancin, which is
      expected to receive FDA approval in 2008, appears to be a promising new
      antimicrobial agent for the treatment of cSSTIs.

PMID- 18728716
TI  - Factors affecting therapeutic compliance: A review from the patient's
      perspective.
AB  - OBJECTIVE: To explore and evaluate the most common factors causing therapeutic
      non-compliance. METHODS: A qualitative review was undertaken by a literature
      search of the Medline database from 1970 to 2005 to identify studies evaluating
      the factors contributing to therapeutic non-compliance. RESULTS: A total of 102
      articles was retrieved and used in the review from the 2095 articles identified
      by the literature review process. From the literature review, it would appear
      that the definition of therapeutic compliance is adequately resolved. The
      preliminary evaluation revealed a number of factors that contributed to
      therapeutic non-compliance. These factors could be categorized to patient
      centered factors, therapy-related factors, social and economic factors,
      healthcare system factors, and disease factors. For some of these factors, the
      impact on compliance was not unequivocal, but for other factors, the impact was
      inconsistent and contradictory. CONCLUSION: There are numerous studies on
      therapeutic noncompliance over the years. The factors related to compliance may
      be better categorized as "soft" and "hard" factors as the approach in countering
      their effects may differ. The review also highlights that the interaction of the
      various factors has not been studied systematically. Future studies need to
      address this interaction issue, as this may be crucial to reducing the level of
      non-compliance in general, and to enhancing the possibility of achieving the
      desired healthcare outcomes.

PMID- 18728719
TI  - Serotonin receptor modulators in the treatment of irritable bowel syndrome.
AB  - The aim of this article is to review the pathophysiology and clinical role of
      serotonin receptor modulators used in the treatment of irritable bowel syndrome.
      Serotonin is an important monoamine neurotransmitter that plays a key role in the
      initiation of peristaltic and secretory refl exes, and in modulation of visceral
      sensations. Several serotonin receptor subtypes have been characterized, of which
      5HT3, 5HT4, and 5HT1b are the most important for GI function. 5HT4 agonists (eg,
      tegaserod) potentiate peristalsis initiated by 5HT1 receptor stimulation. 5HT4
      agonists are therefore useful in constipation predominant form of IBS and in
      chronic constipation. 5HT3 antagonists (Alosetron and Cilansetron) prevent the
      activation of 5HT3 receptors on extrinsic afferent neurons and can decrease the
      visceral pain associated with IBS. These agents also retard small intestinal and
      colonic transit, and are therefore useful in diarrhea-predominant IBS. Tegaserod
      has been demonstrated in several randomized, placebo controlled trials to relieve
      global IBS symptoms as well as individual symptoms of abdominal discomfort,
      number of bowel movements and stool consistency. Several randomized, controlled
      trials have shown that alosetron relieves pain, improves bowel function, and
      provides global symptom improvement in women with diarrhea-predominant irritable
      bowel syndrome. However, ischemic colitis and severe complications of
      constipation have been major concerns leading to voluntary withdrawal of
      Alosetron from the market followed by remarketing with a comprehensive risk
      management program.

PMID- 18728721
TI  - A novel vaccine for cervical cancer: quadrivalent human papillomavirus (types 6,
      11, 16 and 18) recombinant vaccine (Gardasil).
AB  - Human papillomaviruses (HPVs) are one of the most common sexually transmitted
      infections and remains a public health problem worldwide. There is strong
      evidence that HPV causes cervical, vulva and vaginal cancers, genital warts and
      recurrent respiratory papillomatosis. The current treatments for HPV-induced
      infections are ineffective and recurrence is common-place. Therefore, to reduce
      the burden of HPV-induced infections, several studies have investigated the effi
      cacy of different prophylactic vaccines in clinical human trials directed against
      HPV types 6, 11, 16, or 18. Notably, these HPV types contribute to a signifi cant
      proportion of disease worldwide. This review will focus on the published results
      of Merck & Co's prophylactic quadrivalent recombinant vaccine targeting HPV types
      6, 11, 16, and 18 (referred to as Gardasil((R))). Data from the Phase III trial
      demonstrated that Gardasil was 100% effi cacious in preventing precancerous
      lesions of the cervix, vulva, and vagina and effective against genital warts. Due
      to the success of these human clinical trials, the FDA approved the registration
      of Gardasil on the 8 June 2006. In addition, since Gardasil has been effi cacious
      for 5 years post vaccination, the longest evaluation of an HPV vaccine, it is
      expected to reduce the incidence of these type specifi c HPV-induced diseases in
      the future.

PMID- 18728722
TI  - Anidulafungin in the treatment of invasive fungal infections.
AB  - More antifungal agents have reached clinical use in the past two decades than at
      any other time. The echinocandins have been a welcome addition to this group,
      with the latest being anidulafungin. There are several lines of evidence to
      support anidulafungin's role as primary therapy for the treatment of invasive
      candidiasis in non-neutropenic patients, and as alternative therapy to
      fluconazole in patients with esophageal candidiasis with azole intolerance or
      triazole-resistant Candida. Pharmacokinetic-pharmacodynamic studies in animals
      have demonstrated superior efficacy, defined as maximal microbial kill, when
      compared to fluconazole, regardless of the fluconazole susceptibility of the
      Candida species. These studies, as well as dose-effect studies in patients, also
      support the currently recommended dose of anidulafungin. A well designed
      randomized controlled trial has demonstrated anidulafungin's efficacy in patients
      with invasive candidiasis. In this paper, we argue that anidulafungin may be
      preferable to fluconazole for the treatment of candidemia. However, as of yet,
      the difference between anidulafungin and the other two licensed echinocandins as
      first-line therapy for invasive candidiasis is unclear. On the other hand, there
      is insufficient evidence as of yet to support first-line use of anidulafungin in
      patients with neutropenia or aspergillosis.

PMID- 18728723
TI  - Treatment of prostate cancer: therapeutic potential of targeted immunotherapy
      with APC8015.
AB  - The body's immune system has some capacity to recognize and attack cancerous
      growths, including prostate cancer. However, various intrinsic characteristics of
      tumor cells usually limit that capacity. Therapeutically administered immunologic
      stimuli, such as APC8015, an individualized, ex vivo stimulation of a patient's
      own antigen presenting cells (APC), are capable of boosting the anti-tumor
      response. Late phase clinical trials of APC8015 (now also called Sipuleucel-T)
      show evidence of slowing disease progression and increasing survival in advanced
      prostate cancer. Such immunotherapeutic approaches hold real promise to provide
      additional useful and welcome weapons against this common malignancy.

PMID- 18728720
TI  - Why does the world need another rotavirus vaccine?
AB  - A "Meeting on Upstream Rotavirus Vaccines and Emerging Vaccine Producers" was
      held at the World Health Organization in Geneva, Switzerland on March 28-30,
      2006. The purpose was to discuss, evaluate, and weigh the importance of
      additional rotavirus vaccine candidates following the successful international
      licensure of rotavirus vaccines by two major pharmaceutical companies
      (GlaxoSmithKline and Merck) that had been in development for many years. Both
      licensed vaccines are composed of live rotaviruses that are delivered orally as
      have been all candidate rotavirus vaccines evaluated in humans. Each is built on
      the experience gained with previous candidates whose development had either been
      discontinued or, in the case of the previously licensed rhesus rotavirus
      reassortant vaccine (Rotashield), was withdrawn by its manufacturer after the
      discovery of a rare association with intussusception. Although which alternative
      candidate vaccines should be supported for development and where this should be
      done are controversial topics, there was general agreement expressed at the
      Geneva meeting that further development of alternative candidates is a high
      priority. This development will help insure that the most safe, effective and
      economic vaccines are available to children in Third World nations where the vast
      majority of the >600,000 deaths due to rotavirus occur each year. This review is
      intended to provide the history and present status of rotavirus vaccines as well
      as a perspective on the future development of candidate vaccines as a means of
      promulgating plans suggested at the Geneva meeting.

PMID- 18728724
TI  - Advances in the use of topical imiquimod to treat dermatologic disorders.
AB  - Imiquimod (IQ) is an immune-response modifying agent, first approved by FDA for
      the topical treatment of external genital and perianal warts in 1997. It induces,
      through stimulation of Toll-like receptors (TLRs) localized on the surface of
      antigen-presenting cells, synthesis and release of several endogenous pro
      inflammatory cytokines such as interferon-alpha (IFN-alpha), tumor necrosis
      factor-alpha (TNF-alpha) and interleukins (IL) 6 and 12, which in turn stimulate
      both the innate and acquired immune pathways, resulting in upregulation of
      natural antiviral and antitumor activity. IQ 5% cream has been used for the
      treatment of a wide variety of dermatologic conditions in which the immune system
      is thought to play a role in regression of the disease. In some disorders, such
      as genital and perianal warts, actinic keratoses, basal cell carcinomas, Bowen's
      disease and molluscum contagiosum, relative safety and efficacy are supported by
      randomized controlled trials of IQ. However, it is common for patients to
      experience local skin reactions, which can range from mild to severe in
      intensity, but usually resolve 1-2 weeks after interrupting treatment. Additional
      randomized trials are encouraged to assess safety and efficacy of IQ in the
      treatment of an even wider range of cutaneous disorders.

PMID- 18728727
TI  - The occurrence of bioactive micromonosporae in aquatic habitats of the Sunshine
      Coast in Australia.
AB  - Screening strategies based on the ecological knowledge of antibiotic producing
      microorganisms and their roles in the natural environment are being increasingly
      employed in the search for novel antibiotic agents. Micromonosporae are common
      inhabitants of aquatic habitats and have proved to be a continuing source of
      novel bioactive compounds including antibacterial and antitumor agents. The
      ecological distribution and frequency of bioactive micromonosporae in Sunshine
      Coast region aquatic habitats were studied through a range of selective isolation
      procedures designed to negatively select against the isolation of unwanted
      microbial taxa commonly associated with marine environments. It was revealed that
      bioactive compound producing species of micromonosporae were present in the
      aquatic habitats of the Sunshine Coast region in Australia.

PMID- 18728726
TI  - Tetrodotoxin--distribution and accumulation in aquatic organisms, and cases of
      human intoxication.
AB  - Many pufferfish of the family Tetraodontidae possess a potent neurotoxin,
      tetrodotoxin (TTX). In marine pufferfish species, toxicity is generally high in
      the liver and ovary, whereas in brackish water and freshwater species, toxicity
      is higher in the skin. In 1964, the toxin of the California newt was identified
      as TTX as well, and since then TTX has been detected in a variety of other
      organisms. TTX is produced primarily by marine bacteria, and pufferfish
      accumulate TTX via the food chain that begins with these bacteria. Consequently,
      pufferfish become non-toxic when they are fed TTX-free diets in an environment in
      which the invasion of TTX-bearing organisms is completely shut off. Although some
      researchers claim that the TTX of amphibians is endogenous, we believe that it
      also has an exogenous origin, i.e., from organisms consumed as food. TTX-bearing
      animals are equipped with a high tolerance to TTX, and thus retain or accumulate
      TTX possibly as a biologic defense substance. There have been many cases of human
      intoxication due to the ingestion of TTX-bearing pufferfish, mainly in Japan,
      China, and Taiwan, and several victims have died. Several cases of TTX
      intoxication due to the ingestion of small gastropods, including some lethal
      cases, were recently reported in China and Taiwan, revealing a serious public
      health issue.

PMID- 18728728
TI  - In utero domoic acid toxicity: a fetal basis to adult disease in the California
      sea lion (Zalophus californianus).
AB  - California sea lions have been a repeated subject of investigation for early life
      toxicity, which has been documented to occur with increasing frequency from late
      February through mid-May in association with organochlorine (PCB and DDT)
      poisoning and infectious disease in the 1970's and domoic acid poisoning in the
      last decade. The mass early life mortality events result from the concentrated
      breeding grounds and synchronization of reproduction over a 28 day post partum
      estrus cycle and 11 month in utero phase. This physiological synchronization is
      triggered by a decreasing photoperiod of 11.48 h/day that occurs approximately 90
      days after conception at the major California breeding grounds. The photoperiod
      trigger activates implantation of embryos to proceed with development for the
      next 242 days until birth. Embryonic diapause is a selectable trait thought to
      optimize timing for food utilization and male migratory patterns; yet from the
      toxicological perspective presented here also serves to synchronize developmental
      toxicity of pulsed environmental events such as domoic acid poisoning. Research
      studies in laboratory animals have defined age-dependent neurotoxic effects
      during development and windows of susceptibility to domoic acid exposure. This
      review will evaluate experimental domoic acid neurotoxicity in developing rodents
      and, aided by comparative allometric projections, will analyze potential prenatal
      toxicity and exposure susceptibility in the California sea lion. This analysis
      should provide a useful tool to forecast fetal toxicity and understand the impact
      of fetal toxicity on adult disease of the California sea lion.

PMID- 18728725
TI  - Domoic acid toxicologic pathology: a review.
AB  - Domoic acid was identified as the toxin responsible for an outbreak of human
      poisoning that occurred in Canada in 1987 following consumption of contaminated
      blue mussels [Mytilus edulis]. The poisoning was characterized by a constellation
      of clinical symptoms and signs. Among the most prominent features described was
      memory impairment which led to the name Amnesic Shellfish Poisoning [ASP]. Domoic
      acid is produced by certain marine organisms, such as the red alga Chondria
      armata and planktonic diatom of the genus Pseudo-nitzschia. Since 1987,
      monitoring programs have been successful in preventing other human incidents of
      ASP. However, there are documented cases of domoic acid intoxication in wild
      animals and outbreaks of coastal water contamination in many regions world-wide.
      Hence domoic acid continues to pose a global risk to the health and safety of
      humans and wildlife. Several mechanisms have been implicated as mediators for the
      effects of domoic acid. Of particular importance is the role played by glutamate
      receptors as mediators of excitatory neurotransmission and the demonstration of a
      wide distribution of these receptors outside the central nervous system,
      prompting the attention to other tissues as potential target sites. The aim of
      this document is to provide a comprehensive review of ASP, DOM induced pathology
      including ultrastructural changes associated to subchronic oral exposure, and
      discussion of key proposed mechanisms of cell/tissue injury involved in DOM
      induced brain pathology and considerations relevant to food safety and human
      health.

PMID- 18728729
TI  - Effects of in vitro brevetoxin exposure on apoptosis and cellular metabolism in a
      leukemic T cell line (Jurkat).
AB  - Harmful algal blooms (HABs) of the toxic dinoflagellate, Karenia brevis, produce
      red tide toxins, or brevetoxins. Significant health effects associated with red
      tide toxin exposure have been reported in sea life and in humans, with
      brevetoxins documented within immune cells from many species. The objective of
      this research was to investigate potential immunotoxic effects of brevetoxins
      using a leukemic T cell line (Jurkat) as an in vitro model system. Viability,
      cell proliferation, and apoptosis assays were conducted using brevetoxin
      congeners PbTx-2, PbTx-3, and PbTx-6. The effects of in vitro brevetoxin exposure
      on cell viability and cellular metabolism or proliferation were determined using
      trypan blue and MTT (1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan),
      respectively. Using MTT, cellular metabolic activity was decreased in Jurkat
      cells exposed to 5 - 10 microg/ml PbTx-2 or PbTx-6. After 3 h, no significant
      effects on cell viability were observed with any toxin congener in concentrations
      up to 10 microg/ml. Viability decreased dramatically after 24 h in cells treated
      with PbTx-2 or -6. Apoptosis, as measured by caspase-3 activity, was
      significantly increased in cells exposed to PbTx-2 or PbTx-6. In summary,
      brevetoxin congeners varied in effects on Jurkat cells, with PbTx-2 and PbTx-6
      eliciting greater cellular effects compared to PbTx-3.

PMID- 18728730
TI  - Non-traditional vectors for paralytic shellfish poisoning.
AB  - Paralytic shellfish poisoning (PSP), due to saxitoxin and related compounds,
      typically results from the consumption of filter-feeding molluscan shellfish that
      concentrate toxins from marine dinoflagellates. In addition to these microalgal
      sources, saxitoxin and related compounds, referred to in this review as STXs, are
      also produced in freshwater cyanobacteria and have been associated with
      calcareous red macroalgae. STXs are transferred and bioaccumulate throughout
      aquatic food webs, and can be vectored to terrestrial biota, including humans.
      Fisheries closures and human intoxications due to STXs have been documented in
      several non-traditional (i.e. non-filter-feeding) vectors. These include, but are
      not limited to, marine gastropods, both carnivorous and grazing, crustacea, and
      fish that acquire STXs through toxin transfer. Often due to spatial, temporal, or
      a species disconnection from the primary source of STXs (bloom forming
      dinoflagellates), monitoring and management of such non-traditional PSP vectors
      has been challenging. A brief literature review is provided for filter feeding
      (traditional) and non-filter feeding (non-traditional) vectors of STXs with
      specific reference to human effects. We include several case studies pertaining
      to management actions to prevent PSP, as well as food poisoning incidents from
      STX(s) accumulation in non-traditional PSP vectors.

PMID- 18728731
TI  - Neurotoxins from marine dinoflagellates: a brief review.
AB  - Dinoflagellates are not only important marine primary producers and grazers, but
      also the major causative agents of harmful algal blooms. It has been reported
      that many dinoflagellate species can produce various natural toxins. These toxins
      can be extremely toxic and many of them are effective at far lower dosages than
      conventional chemical agents. Consumption of seafood contaminated by algal toxins
      results in various seafood poisoning syndromes: paralytic shellfish poisoning
      (PSP), neurotoxic shellfish poisoning (NSP), amnesic shellfish poisoning (ASP),
      diarrheic shellfish poisoning (DSP), ciguatera fish poisoning (CFP) and
      azaspiracid shellfish poisoning (ASP). Most of these poisonings are caused by
      neurotoxins which present themselves with highly specific effects on the nervous
      system of animals, including humans, by interfering with nerve impulse
      transmission. Neurotoxins are a varied group of compounds, both chemically and
      pharmacologically. They vary in both chemical structure and mechanism of action,
      and produce very distinct biological effects, which provides a potential
      application of these toxins in pharmacology and toxicology. This review
      summarizes the origin, structure and clinical symptoms of PSP, NSP, CFP, AZP,
      yessotoxin and palytoxin produced by marine dinoflagellates, as well as their
      molecular mechanisms of action on voltage-gated ion channels.

PMID- 18728732
TI  - A structural modelling study on marine sediments toxicity.
AB  - Quantitative structure-activity relationship models were obtained by applying the
      Molecular Descriptor Family approach to eight ordnance compounds with different
      toxicity on five marine species (arbacia punctulata, dinophilus gyrociliatus,
      sciaenops ocellatus, opossum shrimp, and ulva fasciata). The selection of the
      best among molecular descriptors generated and calculated from the ordnance
      compounds structures lead to accurate monovariate models. The resulting models
      obtained for six endpoints proved to be accurate in estimation (the squared
      correlation coefficient varied from 0.8186 to 0.9997) and prediction (the
      correlation coefficient obtained in leave-one-out analysis varied from 0.7263 to
      0.9984).

PMID- 18728734
TI  - WHAT IS A COCHRANE REVIEW?
AB  - In this era of evidence-based practice, it is important for nurses in all
      settings to understand and have access to high-quality systematic reviews of
      published evidence. This paper introduces a premier resource, the Cochrane
      Collaboration, and reviews mechanisms for accessing its published systematic
      reviews from any practice setting.

PMID- 18728733
TI  - Recreational exposure to low concentrations of microcystins during an algal bloom
      in a small lake.
AB  - We measured microcystins in blood from people at risk for swallowing water or
      inhaling spray while swimming, water skiing, jet skiing, or boating during an
      algal bloom. We monitored water samples from a small lake as a Microcystis
      aeruginosa bloom developed. We recruited 97 people planning recreational
      activities in that lake and seven others who volunteered to recreate in a nearby
      bloom-free lake. We conducted our field study within a week of finding a 10
      microg/L microcystin concentration. We analyzed water, air, and human blood
      samples for water quality, potential human pathogens, algal taxonomy, and
      microcystin concentrations. We interviewed study participants for demographic and
      current health symptom information. Water samples were assayed for potential
      respiratory viruses (adenoviruses and enteroviruses), but none were detected. We
      did find low concentrations of Escherichia coli, indicating fecal contamination.
      We found low levels of microcystins (2 microg/L to 5 microg/L) in the water and
      (<0.1 ng/m(3)) in the aerosol samples. Blood levels of microcystins for all
      participants were below the limit of detection (0.147 microg/L). Given this low
      exposure level, study participants reported no symptom increases following
      recreational exposure to microcystins. This is the first study to report that
      water-based recreational activities can expose people to very low concentrations
      of aerosol-borne microcystins; we recently conducted another field study to
      assess exposures to higher concentrations of these algal toxins.

PMID- 18728736
TI  - Prevalence of claustrophobia and magnetic resonance imaging after coronary artery
      bypass graft surgery.
AB  - BACKGROUND: The purpose of this study was to determine the prevalence of
      claustrophobia in patients undergoing magnetic resonance imaging (MRI) after
      coronary artery bypass graft (CABG) surgery. METHODS: After IRB approval, we
      conducted a substudy of a prospective randomized controlled clinical trial of 311
      patients evaluating administration of tranexamic acid and early saphenous vein
      graft patency with MRI after conventional CABG surgery. Chest tube drainage was
      measured at 6, 12, and 24 hours after surgery. The rate of transfusion and the
      amount of red blood cells (RBC), fresh frozen plasma (FFP), and platelets
      transfused were recorded. RESULTS: A total of 237(76%) patients underwent MRI
      after surgery. 39 (14%, [95% CI, 10.2 to 18.0]) patients experienced severe
      anxiety caused by a fear of enclosed space in the MRI coil necessitating
      termination of the procedure. Patients with claustrophobia were on average 5
      years younger. They were more likely to have diabetes mellitus and hypertension.
      Patients with claustrophobia had increased chest tube drainage during the
      postoperative period. The rate of blood product transfusion was similar between
      the two groups but patients with claustrophobia who were transfused received
      significantly more RBC and FFP than patients without claustrophobia. CONCLUSIONS:
      Postoperative claustrophobia and anxiety, leading to inability to undergo MRI,
      may be more common than previously described.

PMID- 18728737
TI  - The prognostic value of injury severity, location of event, and age at injury in
      pediatric traumatic head injuries.
AB  - AIMS: To estimate the prognostic value of injury severity, location of event, and
      demographic parameters, for symptoms of pediatric traumatic head injury (THI) 4
      years later. METHODS: Data were collected prospectively from Reykjavik City
      Hospital on all patients age 0-19 years, diagnosed with THI (n = 408) during one
      year. Information was collected on patient demographics, location of traumatic
      event, cause of injury, injury severity, and ICD-9 diagnosis. Injury severity was
      estimated according to the Head Injury Severity Scale (HISS). Four years post
      injury, a questionnaire on late symptoms attributed to the THI was sent. RESULTS:
      Symptoms reported were more common among patients with moderate/severe THI than
      among others (p < 0.001). The event location had prognostic value (p < 0.05).
      Overall, 72% of patients with moderate/severe motor vehicle-related THI reported
      symptoms. There was a curvilinear age effect (p < 0.05). Symptoms were least
      frequent in the youngest age group, 0-4 years, and most frequent in the age group
      5-14 years. Gender and urban/rural residence were not significantly related to
      symptoms. CONCLUSIONS: Motor vehicle related moderate/severe THI resulted in a
      high rate of late symptoms. Location had a prognostic value. Patients with motor
      vehicle-related THI need special consideration regardless of injury severity.

PMID- 18728738
TI  - Absence status associated with focal activity and polydipsia-induced
      hyponatremia.
AB  - We report a case of de novo absence status associated with focal discharge and
      polydipsia-induced hyponatremia. Nonconvulsive status epilepticus (NCSE) is
      classified as absence status or complex partial status. Absence status is
      characterized by bilateral synchronized spike and wave complex bursts and a
      variety of conscious disturbances. Possible precipitating factors for NCSE
      include benzodiazepine withdrawal, excessive use of psychotropic drugs, and
      electrolyte imbalances. Hyponatremia is a rare precipitating factor. In this
      case, the patient was 59 years old and had suffered from primary insomnia but had
      no history of epilepsy. NCSE improved by means of saline infusion. However after
      recovery from NCSE EEG revealed some spikes in the left frontal area. Absence
      seizures can also show generalized spike and slow waves, and cases of focal
      lesion-associated absence seizures have been reported. Although absence seizures
      and absence status are two distinct conditions, they should not be considered
      together. We assumed that hyponatremia induced by polydipsia precipitated
      epileptogenicity in the left frontal area, and then focal activity secondarily
      generalized and resulted in absence status.

PMID- 18728739
TI  - Marital status, depressive episodes, and short-term prognosis of patients with
      acute coronary syndrome: Greek study of acute coronary syndrome (GREECS).
AB  - The association between marital status and short-term prognosis of patients
      hospitalized for acute coronary syndrome (ACS) was evaluated. From October 2003
      to September 2004, a sample of 6 hospitals located in Greek regions was selected,
      and almost all survivors after an ACS were enrolled into the study (2172 patients
      were included in the study; 76% were men). The in-hospital mortality rate was
      3.2% in male patients and 5.7% in female patients (p = 0.009). Never-married
      patients had 2.8-times higher risk of dying during hospitalization compared with
      married, after adjusting for various confounders (p < 0.01, attributable risk =
      64%). Furthermore, never-married had 2.7-times higher risk of dying during the
      first 30-days following hospitalization compared with married (p < 0.01,
      attributable risk = 62%). Moderate depressive symptoms 3.26-fold (95% CI 1.40
      7.11) the risk of recurrent events, while severe depressive symptoms were
      associated with 8.2-fold (95% CI 3.98-17.1) higher risk of events. No interaction
      was observed between marital status and depression on 30-day prognosis of ACS
      patients (p > 0.5). People who were not-married and depressed at the time of an
      acute cardiac episode were at higher risk of fatal events than people who were
      married, irrespective of depression status and other characteristics.

PMID- 18728740
TI  - Update on the use of pramipexole in the treatment of Parkinson's disease.
AB  - Pramipexole is a non-ergot dopamine agonist shown to be efficacious in the
      treatment of Parkinson's disease (PD). This review addresses the literature
      concerning pramipexole's efficacy in treating motor and non-motor symptoms in PD,
      its impact on the development of dyskinesias and response fluctuations, the issue
      of neuroprotection, and the risk for developing adverse events such as increased
      somnolence, attacks of sudden onset of sleep, cardiac valvulopathy and impulse
      control disturbances.

PMID- 18728741
TI  - Varenicline in the treatment of tobacco dependence.
AB  - Varenicline, a partial agonist of alpha(4)beta(2) nicotinic acetylcholine
      receptors, is the most recently approved drug for smoking cessation. This paper
      reviews the outcomes of Phase 2 and Phase 3 clinical trials that assess the
      efficacy of varenicline in comparison to placebo and other smoking cessation
      pharmacotherapies, ie, sustained-release bupropion (bupropion SR) and nicotine
      transdermal patch. Varenicline has higher abstinence rates than placebo and the
      alternative active treatments at the end of standard regimen treatment periods.
      Significantly higher abstinence rates were also found with varenicline in
      comparison to both placebo and bupropion SR at the end of a 40-week non-treatment
      follow-up period. Varenicline typically tripled the abstinence rates compared
      with placebo. In addition, varenicline reduced craving and withdrawal symptoms as
      well as some of the positive experiences associated with smoking to a greater
      extent than placebo, bupropion SR, and nicotine replacement therapy (NRT). These
      findings are consistent with the proposed agonist/antagonist effects of
      varenicline. Preliminary studies assessing individual variables such as smoking
      dependency level and smoking reinforcement types provide justification to examine
      further the effects of varenicline according to these individual factors.
      Outcomes from such research could improve our understanding of varenicline's
      mechanism of action and could ultimately help clinicians to develop
      individualized smoking cessation programs. Also, given varenicline's ability to
      reduce the reward from smoking, it might be helpful to use it before cessation to
      motivate or prepare smokers for a quit attempt.

PMID- 18728742
TI  - Epilepsy and suicide: pathogenesis, risk factors, and prevention.
AB  - Depression and suicide tendencies are common in chronic diseases, especially in
      epilepsy and diabetes. Suicide is one of the most important causes of death, and
      is usually underestimated. We have analyzed several studies that compare
      mortality as a result of suicide in epileptic patients and in the general
      population. All the studies show that epileptic patients have a stronger tendency
      toward suicide than healthy controls. Moreover it seems that some kinds of
      epilepsy have a higher risk for suicide (temporal-lobe epilepsy). Among the risk
      factors are surgery therapy (suicide tendency five times higher than patients in
      pharmacological therapy), absence of seizures for a long time, especially after
      being very frequent, and psychiatric comorbidity (major depression, anxiety
      depression disorders, personality disorders, substance abuse, psychoses). The aim
      of the review was to analyze the relationship between suicide and epilepsy, to
      identify the major risk factors, and to analyze effective treatment options.

PMID- 18728743
TI  - Increased mRNA expression of cytochrome oxidase in dorsal raphe nucleus of
      depressive suicide victims.
AB  - Suicidal behavior is a problem with important social repercussions. Some groups
      of the population show a higher risk of suicide; for example, depression,
      alcoholism, psychosis or drug abuse frequently precedes suicidal behavior.
      However, the relationship between metabolic alterations in the brain and
      premorbid clinical symptoms of suicide remains uncertain. The serotonergic and
      noradrenergic systems have frequently been, implicated in suicidal behavior and
      the amount of serotonin in the brain and CSF of suicide victims has been found to
      be low compared with normal subjects. However, there are contradictory results
      regarding the role of noradrenergic neurons in the mediation of suicide attempts,
      possibly reflecting the heterogeneity of conditions that lead to a common
      outcome. In the present work we focus on the subgroup of suicide victims that
      share a common diagnosis of major depression. Based on post-mortem studies
      analyzing mRNA expression by in situ hybridization, serotonergic neurons from the
      dorsal raphe nucleus (DRN) from depressive suicide victims are seen to over
      express cytochrome oxidase mRNA. However, no corresponding changes were found in
      the expression of tyrosine hydroxylase (TH) mRNA in the noradrenergic neurons of
      the Locus Coeruleus (LC). These results suggest that, despite of the low levels
      of serotonin described in suicide victims, the activity of DRN neurons could
      increase in the suicidally depressed, probably due to the over activation of
      serotonin re-uptake. No alteration was found in noradrenergic neurons, suggesting
      that they play no crucial role in the suicidal behavior of depressive patients.

PMID- 18728744
TI  - Review of the clinical evidence for interferon beta 1a (Rebif) in the treatment
      of multiple sclerosis.
AB  - Interferon (INF) beta 1a 22 or 44 mug (Rebif((R))) administered s.c. 3 times a
      week (t.i.w) is a well established immunomodulating treatment for relapsing
      remitting multiple sclerosis (RRMS). This review focuses on its mechanisms of
      action, evidence of efficacy, safety, and tolerability. Several pharmacodynamic
      properties explain the immunomodulatory actions of INF beta 1a 22 or 44 mug s.c.
      t.i.w. Pivotal trials and post-marketing studies proved that the drug is
      effective in reducing disease activity and likely in slowing disease progression.
      Head-to-head comparative studies with other marketed INFs beta in RRMS suggested
      a better therapeutic response associated with higher doses and frequency of
      administration of Rebif((R)). Additional evidence indicated a beneficial effect
      of INF beta 1a in patients with clinically isolated syndromes (CIS) suggestive of
      MS, as treatment reduced time to conversion to clinically definite (CD) disease.
      Further, although the drug did not prove to slow time to progression there were
      benefits on relapse- and MRI-related secondary outcome measures in secondary
      progressive (SP) MS. Pivotal trials, their cross-over extensions, and post
      marketing studies consistently showed that INF beta 1a 22 or 44 mug s.c. t.i.w.
      is safe and well tolerated, as adverse drug reactions are usually mild and
      manageable.

PMID- 18728746
TI  - Effects of risperidone and olanzapine on remnant-like lipoprotein particle
      cholesterol (RLP-C) in schizophrenic patients.
AB  - Second generation antipsychotics are associated with the risk of metabolic
      disorders such as diabetes mellitus and hyperlipidemia. Remnant-like lipoprotein
      particles cholesterol (RLP-C) are a known risk factor for cardiovascular events.
      The present study was performed to determine possible differences in fasting
      blood RLP-C levels between schizophrenic patients treated with risperidone as
      compared to olanzapine. Patients on olanzapine had significantly higher RLP-C
      levels than those on risperidone (p < 0.01). In olanzapine-treated patients there
      was no abnormality in fasting blood glucose levels, but fasting insulin levels
      and homeostasis model assessment of insulin resistance (HOMA-IR) were elevated.
      RLP-C levels were significantly correlated with plasma triglyceride
      concentrations in both the olanzapine- (p < 0.01) and risperidone-treated
      patients (p < 0.01). The regression line slope was greater for the olanzapine
      group, suggesting a greater influence of olanzapine on RLP-C. There was a
      significant correlation between RLP-C and HOMA-IR in the risperidone group (p <
      0.01) but not in the olanzapine group (p = 0.80). These results suggest that
      blood glucose monitoring may not be sufficient to detect metabolic disorder and
      that measurement of RLP-C might be helpful for the screening for metabolic
      disorders associated with olanzapine therapy.

PMID- 18728745
TI  - Treatment of adults with attention-deficit/hyperactivity disorder.
AB  - This review focuses on the treatment of attention deficit hyperactivity disorder
      (ADHD) in adults. It briefly addresses prevalence, diagnostic and differential
      diagnostic issues specific to adults. Stimulant medication, non-stimulant
      medication, and psychosocial treatments are thoroughly reviewed. For each class
      of medication possible mechanism of action, efficacy and side effects are
      summarized. Special attention is given to the pharmacological treatment for
      patients with adult ADHD and various comorbidities. In summary, stimulant
      medications are most effective and combined medication and psychosocial treatment
      is the most beneficial treatment option for most adult patients with ADHD.

PMID- 18728747
TI  - Homocysteine and carotid intima-media thickness in ischemic stroke patients are
      not correlated.
AB  - INTRODUCTION: Hyperhomocysteinemia has been linked to cardiovascular morbidity
      and mortality by numerous authors. Whether this association is causal or not
      remains uncertain. The aim of the study was to investigate the association of
      hyperhomocysteinemia with the degree of carotid atherosclerosis in stroke
      patients. METHODS: We studied 97 Greek patients in our stroke unit who were
      hospitalized as a result of ischemic stroke between March 2006 and May 2007. The
      patients were divided into two groups: the first (52 patients) included stroke
      patients with serum levels of homocysteine below 15 mumol/L, but in the second
      group (45 patients) serum homocysteine exceeded this value. We measured carotid
      intima-media thickness (cIMT) in all patients and correlated it with serum
      homocysteine. RESULTS: The mean homocysteine concentration was 11.5 mumol/L in
      the first group and 21.5 mumol/L in the second group. Carotid IMT was 1.012 mm in
      the first group, and 1.015 mm in the second group, an insignificant difference.
      On the contrary, serum folate concentration was 21.3 nmol/L in the first group
      compared with 16.7 nmol/L in the second group (p < 0.001). VitB12 was 401 pmol/L
      in the first group and 340 pmol/L in the second group, a statistically
      significant difference (p < 0.001). CONCLUSIONS: Serum levels of homocysteine
      were not correlated with cIMT in ischemic stroke patients. Both folate and vitB12
      were decreased in hyperhomocysteinemic ischemic stroke patients.

PMID- 18728749
TI  - Levels of vascular endothelial growth factor-A165b (VEGF-A165b) are elevated in
      experimental glaucoma.
AB  - PURPOSE: Although ischemia has previously been suggested to contribute to the
      pathogenesis of glaucoma, neovascularization is not implicated in glaucoma.
      Because vascular endothelial growth factor-A (VEGF-A) is a key mediator in
      neovascularization response, we investigated the levels of the major pro
      angiogenic (VEGF-A164) and anti-angiogenic VEGF-A subtypes (VEGF-A165b) in the
      retina during experimental glaucoma. METHODS: Glaucoma was induced unilaterally
      in rats by injecting 1.9 M hypertonic saline solution in the episcleral veins.
      The contralateral eye served as the control. The intraocular pressure (IOP) of
      each eye was measured via Tonopen in conscious rats. Eyes were enucleated either
      on the 5th or the 10th day of elevated IOP. Whole retinal lysates were separated
      by SDS-PAGE and transferred to PVDF membranes. Levels of VEGF-A164 and VEGF-A165b
      were analyzed by western blotting using specific antibodies. In a different group
      of rats, retinal ganglion cells were retrogradely labeled by injecting Fluorogold
      in the superior colliculus a week before the induction of glaucoma. After the
      eyes were enucleated on the fifth day of elevated IOP, posterior eye cups were
      sectioned using a cryostat. Levels and localization of VEGF-A164 and VEGF-A165b
      were examined in retinal sections by immunohistochemistry. RESULTS: VEGF-A164
      levels remained unchanged between the control and glaucomatous retinas after five
      days (p=0.341) and 10 days of elevated IOP (p=0.117). The presence of the anti
      angiogenic VEGF-A isoform has not been previously reported in the rat. An
      antibody specific to VEGF-A165b detected the anti-angiogenic protein in the rat
      retina. VEGF-A165b levels were significantly increased (2.33+/-0.44 fold,
      p=0.014) in the glaucomatous retinas compared to those in controls after five
      days of elevated IOP. VEGF-A165b levels were not different (p=0.864) between the
      control and glaucomatous retinas following 10 days of elevated IOP. Expression of
      both VEGF-A164 and VEGF-A165b were observed in the retinal ganglion cells (RGC)
      and inner nuclear layer (INL). CONCLUSIONS: Five day elevation of IOP leads to an
      increase in the anti-angiogenic VEGF-A165b levels but not in the pro-angiogenic
      VEGF-A164 levels in the glaucomatous retina. VEGF-A165b levels return to baseline
      after 10 days of elevated IOP, and VEGF-A164 levels remain unchanged. We
      speculate that the short-term elevation of VEGF-A165b levels and/or the unchanged
      levels of VEGF-A164 contribute to the lack of neovascularization in the
      glaucomatous retina.

PMID- 18728750
TI  - Conjunctival mast cell as a mediator of eosinophilic response in ocular allergy.
AB  - PURPOSE: To determine the contribution of conjunctival mast cells to the allergen
      specific inflammatory responses in eyes with allergic conjunctivitis and to test
      the hypothesis that mast cells act as mediators of the early phase response.
      METHODS: The participation of mast cells in allergen-induced inflammatory cell
      recruitment was studied in an experimental murine model of allergic
      conjunctivitis. Experimental allergic conjunctivitis was induced by a single or
      multiple sensitizing injections of an allergen. The conjunctiva of allergen
      sensitized, mast cell-deficient (Kit(w)/Kit(w-v)) mice were reconstituted with
      conjunctival mast cells isolated from naive wild type mice by subconjunctival
      transfer. Kit(w)/Kit(w-v) mice and conjunctival mast cell reconstituted
      Kit(w)/Kit(w-v) mice were evaluated for early phase reactions and late phase
      inflammatory responses. RESULTS: The early phase response was minimal in
      Kit(w)/Kit(w-v) mice after both a single injection and multiple sensitization
      injections of the allergen. The early phase responses were fully restored
      following adoptive transfer of isolated conjunctival mast cells from naive wild
      type mice. Eosinophilic inflammatory responses were significantly depressed in
      Kit(w)/Kit(w-v) mice without the impairment of allergen-specific priming.
      Reconstitution of the conjunctiva of Kit(w)/Kit(w-v) mice with mast cells from
      wild type mice fully restored the allergen-specific eosinophilic responses but
      not the neutrophilic responses. CONCLUSIONS: Our data indicate that conjunctival
      mast cells are essential for eosinophilic inflammation but not for neutrophilia
      in allergic conjunctivitis that is mediated by mast cell activation.

PMID- 18728751
TI  - Pro370Leu MYOC gene mutation in a large Chinese family with juvenile-onset open
      angle glaucoma: correlation between genotype and phenotype.
AB  - PURPOSE: Glaucoma is the leading cause of irreversible blindness worldwide. Most
      of the cases are primary open angle glaucoma (POAG). POAG is a genetically
      heterogenous disease; autosomal dominance is the most frequent type of monogenic
      inheritance. In this study, we identified the genotype of a MYOC mutation and
      investigated the phenotype of a Chinese juvenile-onset open angle glaucoma (JOAG)
      pedigree (GZ.1 pedigree). METHODS: Blood samples were obtained from 24
      participants. We performed sequence and gene linkage analysis in the GZ.1
      pedigree retrospectively. Comprehensive ophthalmologic examinations were
      performed for each family member. Pharmacological treatment or filtering surgery
      was performed as needed according to the intraocular pressure (IOP) of each
      individual. RESULTS: A Pro370Leu myocilin mutation located in exon 3 of MYOC was
      identified in 24 members of the GZ.1 pedigree. Sixteen patients had juvenile
      onset primary open-angle glaucoma (JOAG), and the others participating in the
      project had no such genotype. Analysis of polymorphic microsatellite markers
      indicated that the disease in GZ.1 is autosomal dominant inheritance. The
      patients in GZ.1 are characterized by early age of onset (before 35 years of
      age), severe clinical presentations, and high intraocular pressure unresponsive
      to pharmacological treatment; requiring 89.5% of the patients to undergo
      filtering surgery. Fortunately, the success rate of surgery was high. None of the
      patients required further medical treatment and only one demonstrated low IOP
      fundus changes. CONCLUSIONS: This is the first evidence of a founder effect for a
      Pro370Leu myocilin mutation in a Chinese POAG pedigree. The family with the
      Pro370Leu myocilin mutation presents with juvenile-onset glaucoma. After 10 years
      of follow-up, it is evident that the mutation is closely associated with the
      phenotype of the patients. Analysis of MYOC in JOAG patients may enable the
      identification of at-risk individuals and help prevent disease progression toward
      the degeneration of the optic nerve, and may also contribute to genetic
      counseling.

PMID- 18728748
TI  - Role of phosphodiesterase 5 in synaptic plasticity and memory.
AB  - Phosphodiesterases (PDEs) are enzymes that break down the phosphodiesteric bond
      of the cyclic nucleotides, cAMP and cGMP, second messengers that regulate many
      biological processes. PDEs participate in the regulation of signal transduction
      by means of a fine regulation of cyclic nucleotides so that the response to cell
      stimuli is both specific and activates the correct third messengers. Several PDE
      inhibitors have been developed and used as therapeutic agents because they
      increase cyclic nucleotide levels by blocking the PDE function. In particular,
      sildenafil, an inhibitor of PDE5, has been mainly used in the treatment of
      erectile dysfunction but is now also utilized against pulmonary hypertension.
      This review examines the physiological role of PDE5 in synaptic plasticity and
      memory and the use of PDE5 inhibitors as possible therapeutic agents against
      disorders of the central nervous system (CNS).

PMID- 18728752
TI  - Gamma-synuclein as a marker of retinal ganglion cells.
AB  - PURPOSE: Previous studies have described gamma-synuclein as a protein highly
      expressed in retinal ganglion cells (RGCs), and a loss of RGCs correlates with a
      downregulation of gamma-synuclein gene expression in glaucoma. Here we asked
      whether gamma-synuclein expression in the retina can be considered a specific
      marker of RGCs. METHODS: gamma-Synuclein expression was examined with
      immunohistochemistry in retinal sections from normal and glaucomatous human eyes.
      Primary cultures of RGCs from Sprague-Dawley rats purified by sequential
      immunopanning using a monoclonal antibody to Thy1-1, cultures of A7 immortalized
      optic nerve astrocytes from newborn rats, and the immortalized RGC-5 cell line
      were studied using immunofluorescence and quantitative RT-PCR. RESULTS: gamma
      Synuclein was highly expressed in RGCs in the human retina and was localized in
      cytoplasm adjacent to the RGC nuclear marker, Brn-3a. Axons of RGCs were
      immunopositive for gamma-synuclein in the nerve fiber layer (NFL), the lamina
      cribrosa and the retrobulbar optic nerve. In the optic nerve of glaucoma
      patients, axon swellings were likewise immunopositive, whereas in the retina of
      patients with retinoblastoma, NFL staining appeared reduced. In primary rat RGCs
      and in immortalized RGC-5 cultures, gamma-synuclein was localized predominantly
      in the perinuclear area and in cell processes. Among rat retinal cells in
      culture, all Brn-3a positive cells were stained with a gamma-synuclein antibody;
      rare gamma-synuclein-positive cells were not stained by the Brn-3a antibody.
      CONCLUSIONS: gamma-Synuclein is selectively and abundantly expressed in human
      RGCs in vivo, primary rat RGCs in vitro, and immortalized RGC-5 cells. In
      pathology, gamma-synuclein abundance may vary between RGC somas and axons.
      Coincident Brn-3a and gamma-synuclein expression suggests that strong gamma
      synuclein expression can be considered a marker of RGCs. Future translational
      approaches might include using a gamma-synuclein promoter for the specific
      delivery of siRNA or therapeutic proteins to RGCs.

PMID- 18728753
TI  - The neural correlates of desire.
AB  - In an event-related fMRI study, we scanned eighteen normal human subjects while
      they viewed three categories of pictures (events, objects and persons) which they
      classified according to desirability (desirable, indifferent or undesirable).
      Each category produced activity in a distinct part of the visual brain, thus
      reflecting its functional specialization. We used conjunction analysis to learn
      whether there is a brain area which is always active when a desirable picture is
      viewed, regardless of the category to which it belongs. The conjunction analysis
      of the contrast desirable > undesirable revealed activity in the superior orbito
      frontal cortex. This activity bore a positive linear relationship to the declared
      level of desirability. The conjunction analysis of desirable > indifferent
      revealed activity in the mid-cingulate cortex and in the anterior cingulate
      cortex. In the former, activity was greater for desirable and undesirable stimuli
      than for stimuli classed as indifferent. Other conjunction analyses produced no
      significant effects. These results show that categorizing any stimulus according
      to its desirability activates three different brain areas: the superior orbito
      frontal, the mid-cingulate, and the anterior cingulate cortices.

PMID- 18728754
TI  - Horizontal gene transfers link a human MRSA pathogen to contagious bovine
      mastitis bacteria.
AB  - BACKGROUND: Acquisition of virulence factors and antibiotic resistance by many
      clinically important bacteria can be traced to horizontal gene transfer (HGT)
      between related or evolutionarily distant microflora. Comparative genomic
      analysis has become an important tool for identifying HGT DNA in emerging
      pathogens. We have adapted the multi-genome alignment tool EvoPrinter to
      facilitate discovery of HGT DNA sequences within bacterial genomes and within
      their mobile genetic elements. PRINCIPAL FINDINGS: EvoPrinter analysis of 13
      different Staphylococcus aureus genomes revealed that one of the human isolates,
      the hospital epidemic methicillin-resistant MRSA252 strain, uniquely shares
      multiple putative HGT DNA sequences with different causative agents of bovine
      mastitis that are not found in the other human S. aureus isolates. MRSA252 shares
      over 14 different DNA sequence blocks with the bovine mastitis ET3 S. aureus
      strain RF122, and many of the HGT DNAs encode virulence factors. EvoPrinter
      analysis of the MRSA252 chromosome also uncovered virulence-factor encoding HGT
      events with the genome of Listeria monocytogenes and a Staphylococcus
      saprophyticus associated plasmid. Both bacteria are also causal agents of
      contagious bovine mastitis. CONCLUSIONS: EvoPrinter analysis reveals that the
      human MRSA252 strain uniquely shares multiple DNA sequence blocks with different
      causative agents of bovine mastitis, suggesting that HGT events may be occurring
      between these pathogens. These findings have important implications with regard
      to animal husbandry practices that inadvertently enhance the contact of human and
      livestock bacterial pathogens.

PMID- 18728755
TI  - Truncation of retinoschisin protein associated with a novel splice site mutation
      in the RS1 gene.
AB  - PURPOSE: To present the ocular findings of a Hungarian family with X-linked
      juvenile retinoschisis (XLRS) and to reveal a novel putative splice mutation
      leading to serious truncation of retinoschisin (RS1) protein. Our genetic results
      were compared to a mouse model of XLRS. METHODS: Complete ophthalmic examinations
      were performed on five members (two male patients, two female carriers, and one
      healthy fraternal male twin) of the family. The examinations included optical
      coherence tomography (OCT) and full-field and multifocal electroretinography
      (mfERG). OCT and ERG results were compared to the normative database of our
      laboratory. All exons and the flanking intronic regions of the RS1 gene were
      amplified by polymerase chain reaction and directly sequenced in all family
      members and in 50 male controls. RESULTS: Typical microcystic foveal changes were
      found on fundoscopy and OCT in two male patients. Large foveal and smaller
      perifoveal cysts were detected by OCT in the inner nuclear layer and another
      deeper retinal cleavage in the photoreceptor layer. The standard combined b-wave
      amplitudes and b/a amplitude ratios of full-field ERGs of the male patients were
      decreased compared with controls, but the typical "negative-type" ERG was not
      observed. The amplitudes of mfERGs were reduced in all rings but mainly in the
      central part of the examined retina. Implicit times were delayed across almost
      the whole testing field. Female carriers and the healthy fraternal twin brother
      were without any symptoms and had normal clinical examination results, but the
      implicit times of female carriers were delayed in all rings. DNA sequence
      analyses revealed a novel putative splice mutation (c.78+1G>C) in the splice
      donor site of intron 2 in RS1 of two male patients and two female carriers.
      Mutations were absent in the 50 control samples. CONCLUSIONS: Male patients
      exhibited typical bilateral foveal retinoschisis in two retinal layers and
      characteristic ERG changes. The inheritance of the novel putative splice mutation
      (c.78+1G>C) followed the classic inheritance of an X-linked recessive disease in
      two male patients and two female obligate carriers. There are two possible ways
      the c.78+1G>C splice site mutation may lead to frameshift and introduce a
      premature termination codon at the beginning of exon 3: after activation of the
      next cryptic splice site by a 10 bp insertion or after exon skipping by a 26 bp
      deletion. The splice site mutation in the second intron of RS1 identified in
      these XLRS patients is practically identical to the N-ethyl-N-nitrosourea (ENU)
      induced splice site mutation in the mouse model of XLRS described by the
      Tennessee Mouse Genome Consortium. The genetic findings of the mutant mouse model
      confirm and support our human results.

PMID- 18728757
TI  - Water Dynamics in Nafion Fuel Cell Membranes: the Effects of Confinement and
      Structural Changes on the Hydrogen Bond Network.
AB  - The complex environments experienced by water molecules in the hydrophilic
      channels of Nafion membranes are studied by ultrafast infrared pump-probe
      spectroscopy. A wavelength dependent study of the vibrational lifetime of the O-D
      stretch of dilute HOD in H(2)O confined in Nafion membranes provides evidence of
      two distinct ensembles of water molecules. While only two ensembles are present
      at each level of membrane hydration studied, the characteristics of the two
      ensembles change as the water content of the membrane changes. Time dependent
      anisotropy measurements show that the orientational motions of water molecules in
      Nafion membranes are significantly slower than in bulk water and that lower
      hydration levels result in slower orientational relaxation. Initial wavelength
      dependent results for the anisotropy show no clear variation in the time scale
      for orientational motion across a broad range of frequencies. The anisotropy
      decay is analyzed using a model based on restricted orientational diffusion
      within a hydrogen bond configuration followed by total reorientation through jump
      diffusion.

PMID- 18728756
TI  - Cyan fluorescent protein expression in ganglion and amacrine cells in a thy1-CFP
      transgenic mouse retina.
AB  - PURPOSE: To characterize cyan fluorescent protein (CFP) expression in the retina
      of the thy1-CFP (B6.Cg-Tg(Thy1-CFP)23Jrs/J) transgenic mouse line. METHODS: CFP
      expression was characterized using morphometric methods and immunohistochemistry
      with antibodies to neurofilament light (NF-L), neuronal nuclei (NeuN), POU-domain
      protein (Brn3a) and calretinin, which immunolabel ganglion cells, and syntaxin 1
      (HPC-1), glutamate decarboxylase 67 (GAD(67)), GABA plasma membrane transporter-1
      (GAT-1), and choline acetyltransferase (ChAT), which immunolabel amacrine cells.
      RESULTS: CFP was extensively expressed in the inner retina, primarily in the
      inner plexiform layer (IPL), ganglion cell layer (GCL), nerve fiber layer, and
      optic nerve. CFP fluorescent cell bodies were in all retinal regions and their
      processes ramified in all laminae of the IPL. Some small, weakly CFP fluorescent
      somata were in the inner nuclear layer (INL). CFP-containing somata in the GCL
      ranged from 6 to 20 microm in diameter, and they had a density of 2636+/-347
      cells/mm2 at 1.5 mm from the optic nerve head. Immunohistochemical studies
      demonstrated colocalization of CFP with the ganglion cell markers NF-L, NeuN,
      Brn3a, and calretinin. Immunohistochemistry with antibodies to HPC-1, GAD(67),
      GAT-1, and ChAT indicated that the small, weakly fluorescent CFP cells in the INL
      and GCL were cholinergic amacrine cells. CONCLUSIONS: The total number and
      density of CFP-fluorescent cells in the GCL were within the range of previous
      estimates of the total number of ganglion cells in the C57BL/6J line. Together
      these findings suggest that most ganglion cells in the thy1-CFP mouse line 23
      express CFP. In conclusion, the thy1-CFP mouse line is highly useful for studies
      requiring the identification of ganglion cells.

PMID- 18728758
TI  - Assessment of Semiempirical Quantum Mechanical Methods for the Evaluation of
      Protein Structures.
AB  - The ability to discriminate native structures from computer-generated misfolded
      ones is key to predicting the three-dimensional structure of a protein from its
      amino acid sequence. Here we describe an assessment of semiempirical methods for
      discriminating native protein structures from decoy models. The discrimination of
      decoys entails an analysis of a large number of protein structures, and provides
      a large-scale validation of quantum mechanical methods and their ability to
      accurately model proteins. We combine our analysis of semiempirical methods with
      a comparison of an AMBER force field to discriminate decoys in conjunction with a
      continuum solvent model. Protein decoys provide a rigorous and reliable benchmark
      for the evaluation of scoring functions, not only in their ability to accurately
      identify native structures but also to be computationally tractable to sample a
      large set of non-native models.

PMID- 18728760
TI  - Azaspiracid shellfish poisoning: a review on the chemistry, ecology, and
      toxicology with an emphasis on human health impacts.
AB  - Azaspiracids (AZA) are polyether marine toxins that accumulate in various
      shellfish species and have been associated with severe gastrointestinal human
      intoxications since 1995. This toxin class has since been reported from several
      countries, including Morocco and much of western Europe. A regulatory limit of
      160 microg AZA/kg whole shellfish flesh was established by the EU in order to
      protect human health; however, in some cases, AZA concentrations far exceed the
      action level. Herein we discuss recent advances on the chemistry of various AZA
      analogs, review the ecology of AZAs, including the putative progenitor algal
      species, collectively interpret the in vitro and in vivo data on the toxicology
      of AZAs relating to human health issues, and outline the European legislature
      associated with AZAs.

PMID- 18728759
TI  - Ageing in a eusocial insect: molecular and physiological characteristics of life
      span plasticity in the honey bee.
AB  - Commonly held views assume that ageing, or senescence, represents an inevitable,
      passive, and random decline in function that is strongly linked to chronological
      age. In recent years, genetic intervention of life span regulating pathways, for
      example, in Drosophila as well as case studies in non-classical animal models,
      have provided compelling evidence to challenge these views.Rather than
      comprehensively revisiting studies on the established genetic model systems of
      ageing, we here focus on an alternative model organism with a wild type
      (unselected genotype) characterized by a unique diversity in longevity - the
      honey bee.Honey bee (Apis mellifera) life span varies from a few weeks to more
      than 2 years. This plasticity is largely controlled by environmental factors.
      Thereby, although individuals are closely related genetically, distinct life
      histories can emerge as a function of social environmental change.Another
      remarkable feature of the honey bee is the occurrence of reverted behavioural
      ontogeny in the worker (female helper) caste. This behavioural peculiarity is
      associated with alterations in somatic maintenance functions that are indicative
      of reverted senescence. Thus, although intraspecific variation in organismal life
      span is not uncommon, the honey bee holds great promise for gaining insights into
      regulatory pathways that can shape the time-course of ageing by delaying, halting
      or even reversing processes of senescence. These aspects provide the setting of
      our review.We will highlight comparative findings from Drosophila melanogaster
      and Caenorhabditis elegans in particular, and focus on knowledge spanning from
      molecular- to behavioural-senescence to elucidate how the honey bee can
      contribute to novel insights into regulatory mechanisms that underlie plasticity
      and robustness or irreversibility in ageing.

PMID- 18728762
TI  - Characterization of intracellular and extracellular saxitoxin levels in both
      field and cultured Alexandrium spp. samples from Sequim Bay, Washington.
AB  - Traditionally, harmful algal bloom studies have primarily focused on quantifying
      toxin levels contained within the phytoplankton cells of interest. In the case of
      paralytic shellfish poisoning toxins (PSTs), intracellular toxin levels and the
      effects of dietary consumption of toxic cells by planktivores have been well
      documented. However, little information is available regarding the levels of
      extracellular PSTs that may leak or be released into seawater from toxic cells
      during blooms. In order to fully evaluate the risks of harmful algal bloom toxins
      in the marine food web, it is necessary to understand all potential routes of
      exposure. In the present study, extracellular and intracellular PST levels were
      measured in field seawater samples (collected weekly from June to October 2004
      2007) and in Alexandrium spp. culture samples isolated from Sequim Bay,
      Washington. Measurable levels of intra- and extra-cellular toxins were detected
      in both field and culture samples via receptor binding assay (RBA) and an enzyme
      linked immunosorbent assay (ELISA). Characterization of the PST toxin profile in
      the Sequim Bay isolates by pre-column oxidation and HPLC-fluorescence detection
      revealed that gonyautoxin 1 and 4 made up 65 +/- 9.7% of the total PSTs present.
      Collectively, these data confirm that extracellular PSTs are present during
      blooms of Alexandrium spp. in the Sequim Bay region.

PMID- 18728761
TI  - Yessotoxins, a group of marine polyether toxins: an overview.
AB  - Yessotoxin (YTX) is a marine polyether toxin that was first isolated in 1986 from
      the scallop Patinopecten yessoensis. Subsequently, it was reported that YTX is
      produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium
      polyedrum and Gonyaulax spinifera. YTXs have been associated with diarrhetic
      shellfish poisoning (DSP) because they are often simultaneously extracted with
      DSP toxins, and give positive results when tested in the conventional mouse
      bioassay for DSP toxins. However, recent evidence suggests that YTXs should be
      excluded from the DSP toxins group, because unlike okadaic acid (OA) and
      dinophyisistoxin-1 (DTX-1), YTXs do not cause either diarrhea or inhibition of
      protein phosphatases. In spite of the increasing number of molecular studies
      focused on the toxicity of YTX, the precise mechanism of action is currently
      unknown. Since the discovery of YTX, almost forty new analogues isolated from
      both mussels and dinoflagellates have been characterized by NMR or LC-MS/MS
      techniques. These studies indicate a wide variability in the profile and the
      relative abundance of YTXs in both, bivalves and dinoflagellates. This review
      covers current knowledge on the origin, producer organisms and vectors, chemical
      structures, metabolism, biosynthetic origin, toxicological properties, potential
      risks to human health and advances in detection methods of YTXs.

PMID- 18728763
TI  - Cyanobacterial toxins as allelochemicals with potential applications as
      algaecides, herbicides and insecticides.
AB  - Cyanobacteria ("blue-green algae") from marine and freshwater habitats are known
      to produce a diverse array of toxic or otherwise bioactive metabolites. However,
      the functional role of the vast majority of these compounds, particularly in
      terms of the physiology and ecology of the cyanobacteria that produce them,
      remains largely unknown. A limited number of studies have suggested that some of
      the compounds may have ecological roles as allelochemicals, specifically
      including compounds that may inhibit competing sympatric macrophytes, algae and
      microbes. These allelochemicals may also play a role in defense against potential
      predators and grazers, particularly aquatic invertebrates and their larvae. This
      review will discuss the existing evidence for the allelochemical roles of
      cyanobacterial toxins, as well as the potential for development and application
      of these compounds as algaecides, herbicides and insecticides, and specifically
      present relevant results from investigations into toxins of cyanobacteria from
      the Florida Everglades and associated waterways.

PMID- 18728764
TI  - Mycosporine-like amino acids and marine toxins--the common and the different.
AB  - Marine microorganisms harbor a multitude of secondary metabolites. Among these
      are toxins of different chemical classes as well as the UV-protective mycosporine
      like amino acids (MAAs). The latter form a group of water-soluble, low molecular
      weight (generally < 400) compounds composed of either an aminocyclohexenone or an
      aminocyclohexenimine ring, carrying amino acid or amino alcohol substituents. So
      far there has been no report of toxicity in MAAs but nevertheless there are some
      features they have in common with marine toxins. Among the organisms producing
      MAAs are cyanobacteria, dinoflagellates and diatoms that also synthesize toxins.
      As in cyclic peptide toxins found in cyanobacteria, amino acids are the main
      building blocks of MAAs. Both, MAAs and some marine toxins are transferred to
      other organisms e.g. via the food chains, and chemical modifications can take
      place in secondary consumers. In contrast to algal toxins, the physiological role
      of MAAs is clearly the protection from harmful UV radiation by physical
      screening. However, other roles, e.g. as osmolytes and antioxidants, are also
      considered. In this paper the common characteristics of MAAs and marine toxins
      are discussed as well as the differences.

PMID- 18728765
TI  - Diverse bacterial PKS sequences derived from okadaic acid-producing
      dinoflagellates.
AB  - Okadaic acid (OA) and the related dinophysistoxins are isolated from
      dinoflagellates of the genus Prorocentrum and Dinophysis. Bacteria of the
      Roseobacter group have been associated with okadaic acid producing
      dinoflagellates and have been previously implicated in OA production. Analysis of
      16S rRNA libraries reveals that Roseobacter are the most abundant bacteria
      associated with OA producing dinoflagellates of the genus Prorocentrum and are
      not found in association with non-toxic dinoflagellates. While some polyketide
      synthase (PKS) genes form a highly supported Prorocentrum clade, most appear to
      be bacterial, but unrelated to Roseobacter or Alpha-Proteobacterial PKSs or those
      derived from other Alveolates Karenia brevis or Crytosporidium parvum.

PMID- 18728766
TI  - Gait analysis in demented subjects: Interests and perspectives.
AB  - Gait disorders are more prevalent in dementia than in normal aging and are
      related to the severity of cognitive decline. Dementia-related gait changes
      (DRGC) mainly include decrease in walking speed provoked by a decrease in stride
      length and an increase in support phase. More recently, dual-task related changes
      in gait were found in Alzheimer's disease (AD) and non-Alzheimer dementia, even
      at an early stage. An increase in stride-to-stride variability while usual
      walking and dual-tasking has been shown to be more specific and sensitive than
      any change in mean value in subjects with dementia. Those data show that DRGC are
      not only associated to motor disorders but also to problem with central
      processing of information and highlight that dysfunction of temporal and frontal
      lobe may in part explain gait impairment among demented subjects. Gait
      assessment, and more particularly dual-task analysis, is therefore crucial in
      early diagnosis of dementia and/or related syndromes in the elderly. Moreover,
      dual-task disturbances could be a specific marker of falling at a pre-dementia
      stage.

PMID- 18728767
TI  - COMT inhibition with tolcapone in the treatment algorithm of patients with
      Parkinson's disease (PD): relevance for motor and non-motor features.
AB  - Levodopa is the most effective treatment in Parkinson's disease and the
      association with COMT inhibitors widens its plasma bioavailability and
      effectiveness. Tolcapone is a potent COMT inhibitor whose utilization in PD is
      limited due to safety concerns on liver toxicity. However, recent data indicate
      that if liver function is actively monitored, tolerability is no worse than other
      currently available therapies. By contrast, administration of tolcapone is
      associated with significant clinical improvement and benefit involves also non
      motor features. In this review we discuss the rationale for the use of tolcapone
      in association with levodopa and other treatments in PD, and we provide an
      indirect comparison of current strategies to reduce "off" time. We propose that
      future guidelines include a trial with tolcapone in all PD patients who continue
      to complain about motor fluctuations despite treatment with entacapone and/or MAO
      B inhibitors. Moreover, we suggest that tolcapone should be considered before
      surgical or infusional strategies are applied.

PMID- 18728769
TI  - Relationship between obesity and antipsychotic drug use in the adult population:
      a longitudinal, retrospective claim database study in Primary Care settings.
AB  - OBJECTIVE: To describe the association between obesity and the use of
      antipsychotic drugs (APDs) in adult outpatients followed-up on in five Primary
      Care settings. METHODS: A longitudinal, retrospective design study carried out
      between July 2004 and June 2005, in patients who were included in a claim
      database and for whom an APD treatment had been registered. A body mass index
      (BMI) <30 kg/m(2) was defined as obesity. The main measurements were: use of
      APDs, demographics, medical background and co-morbidities, and clinical
      parameters. Logistic regression analysis and ANCOVA with Bonferroni adjustment
      were applied to correct the model. RESULTS: A total of 42,437 subjects (mean age:
      50.8 (18.4) years; women: 54.5%; obesity: 27.3% [95% confidence intervals (CI),
      26.9%-27.7%]) were analyzed. A total of 1.3% of the patients were receiving APDs,
      without statistical differences in distribution by type of drug (typical: 48.8%;
      atypical: 51.2%). Obesity was associated with the use of APDs [OR = 1.5 (CI: 1.3
      1.8)], hypertension [OR = 2.4 (CI: 2.2-2.5)], diabetes [OR = 1.4 (CI: 1.3-1.5)]
      and dyslipidemia [OR = 1.3 (CI: 1.2-1.4)], p < 0.0001 in all cases. BMI was
      significantly higher in subjects on APDs; 28.8 vs. 27.3 kg/m(2), p = 0.002, and
      remained higher after adjusting by age and sex (mean difference 0.4 (CI: 0.1
      0.7), p < 0.01). After adjusting by age, sex and the Charlson index, obese
      subjects generated higher average annual total costs than nonobese subjects; 811
      (CI: 787-835) vs. 694 (CI: 679-709), respectively, p < 0.001. CONCLUSIONS:
      Obesity was associated with the use of APDs, regardless of the type of drug, and
      with the presence of hypertension, diabetes and dyslipidemia. Obesity was also
      associated with substantially higher health care costs.

PMID- 18728770
TI  - The classification of chronic daily headache in French children and adolescents:
      a comparison between the second edition of the International Classification of
      Headache Disorders and Silberstein-Lipton criteria.
AB  - Few data are available on the applicability of both the criteria proposed by
      Silberstein and Lipton (S-L) and the International Classification of Headache
      Disorders-II (ICHD-II) in the classification of children and adolescents with
      chronic daily headache (CDH). The International Headache Society recently added
      revised criteria (ICHD-IIR) for chronic migraine to its Appendix. We
      retrospectively reviewed all charts of 34 children and adolescents (<17 years)
      with primary CDH presenting to the outpatient clinic of the Universitary
      Department of Neuropediatrics of Lille between February 2004 and February 2006
      and tried to classify their CDH according to both S-L criteria and the recently
      published ICHD-IIR. Thirty-two children (94%) and 33 children (97%) could
      respectively be successfully classified into one subtype of CDH according to the
      S-L classification and the ICHD-IIR. Transformed migraine was the most common
      diagnosis (61.8%), followed by new daily-persistent headache (20.6%) when the S-L
      criteria were used. Twenty-three children and adolescents (67.6%) could be
      classified under one of the migraine categories according to the ICHD-IIR
      classification. We think that both S-L and ICHD-II classifications, when used
      with detailed headache histories and diaries, are adequate to classify chronic
      daily headache in children and adolescents.

PMID- 18728768
TI  - Social anxiety disorder: a review of environmental risk factors.
AB  - Social anxiety disorder (SAD) is a debilitating and chronic illness characterized
      by persistent fear of one or more social or performance situations, with a
      relatively high lifetime prevalence of 7% to 13% in the general population.
      Although the last two decades have witnessed enormous growth in the study of
      biological and dispositional factors underlying SAD, comparatively little
      attention has been directed towards environmental factors in SAD, even though
      there has been much ongoing work in the area. In this paper, we provide a recent
      review and critique of proposed environmental risk factors for SAD, focusing on
      traditional as well as some understudied and overlooked environmental risk
      factors: parenting and family environment, adverse life events, cultural and
      societal factors, and gender roles. We also discuss the need for research design
      improvements and considerations for future directions.

PMID- 18728771
TI  - Quetiapine monotherapy for bipolar depression.
AB  - Bipolar depression is more common, disabling, and difficult-to-treat than the
      manic and hypomanic phases that define bipolar disorder. Unlike the treatment of
      so-called "unipolar" depressions, antidepressants generally are not indicated as
      monotherapies for bipolar depressions and recent studies suggest that -even when
      used in combination with traditional mood stabilizers - antidepressants may have
      questionable value for bipolar depression. The current practice is that mood
      stabilizers are initiated first as monotherapies; however, the antidepressant
      efficacy of lithium and valproate is modest at best. Within this context the role
      of atypical antipsychotics is being evaluated. The combination of olanzapine and
      the antidepressant fluoxetine was the first treatment to receive regulatory
      approval in the US specifically for bipolar I depression. Quetiapine was the
      second medication to be approved for this indication, largely as the result of
      two pivotal trials known by the acronyms of BOLDER (BipOLar DEpRession) I and II.
      Both studies demonstrated that two doses of quetiapine (300 mg and 600 mg given
      once daily at bedtime) were significantly more effective than placebo, with no
      increased risk of patients switching into mania. Pooling the two studies,
      quetiapine was effective for both bipolar I and bipolar II depressions and for
      patients with (and without) a history of rapid cycling. The two doses were
      comparably effective in both studies. Although the efficacy of quetiapine
      monotherapy has been established, much additional research is necessary. Further
      studies are needed to more fully investigate dose-response relationships and
      comparing quetiapine monotherapy to other mood stabilizers (lithium, valproate,
      and lamotrigine) in bipolar depression, both singly and in combination. Head-to
      head studies are needed comparing quetiapine to the olanzapine-fluoxetine
      combination. Longer-term studies are needed to confirm the persistence of
      response and to better gauge effects on metabolic profiles across months of
      therapy. A prospective study of patients specifically seeking treatment for rapid
      cycling and those with a history of treatment-emergent affective shifts also is
      needed. Despite the caveats, as treatment guidelines are revised to incorporate
      new data, the efficacy and tolerability of quetiapine monotherapy must be given
      serious consideration.

PMID- 18728772
TI  - White versus gray matter function as seen on neuropsychological testing following
      bone marrow transplant for acute leukemia in childhood.
AB  - Current theory suggests that neurocognitive late effects of treatments for
      childhood cancer such as difficulties with attention, processing speed and visual
      motor ability are the result of white matter damage. Neuroimaging studies have
      produced a variety of white matter findings. However, although white matter is
      thought to be differentially affected, previous studies have not demonstrated a
      discrepancy between white and gray matter function. The present study included 36
      children treated for childhood leukemia with hematopoietic stem cell transplant
      (HCT). Their performance on neurocognitive measures traditionally thought to
      measure white matter was compared to performance on measures thought to measure
      gray matter function. Composite white and gray matter standard scores were
      created based on neuropsychological measures that individuals with known white or
      gray matter damage perform poorly. As predicted, composite white matter scores
      (mean = 98.1) were significantly lower (t = 2.26, p = 0.03) than composite gray
      matter scores (mean = 102.5). Additionally, as gray matter performance increased,
      the difference between gray and white matter scores increased (R = 0.353, p =
      0.035). Overall, the results of this study support the current theory that white
      matter damage is responsible for the more subtle neurocognitive late effects
      resulting from treatment for childhood leukemia.

PMID- 18728774
TI  - Small scattered fragments do not a dwarf make: biological and archaeological data
      indicate that prehistoric inhabitants of Palau were normal sized.
AB  - Current archaeological evidence from Palau in western Micronesia indicates that
      the archipelago was settled around 3000-3300 BP by normal sized populations;
      contrary to recent claims, they did not succumb to insular dwarfism. BACKGROUND:
      Previous and ongoing archaeological research of both human burial and occupation
      sites throughout the Palauan archipelago during the last 50 years has produced a
      robust data set to test hypotheses regarding initial colonization and subsequent
      adaptations over the past three millennia. PRINCIPAL FINDINGS: Close examination
      of human burials at the early (ca. 3000 BP) and stratified site of Chelechol ra
      Orrak indicates that these were normal sized individuals. This is contrary to the
      recent claim of contemporaneous "small-bodied" individuals found at two cave
      sites by Berger et al. (2008). As we argue, their analyses are flawed on a number
      of different analytical levels. First, their sample size is too small and
      fragmentary to adequately address the variation inherent in modern humans within
      and outside of Palau. Second, the size and stature of all other prehistoric (both
      older and contemporaneous) skeletal assemblages found in Palau fall within the
      normal parameters of modern human variation in the region, indicating this was
      not a case of insular dwarfism or a separate migratory group. Third, measurements
      taken on several skeletal elements by Berger et al. may appear to be from smaller
      bodied individuals, but the sizes of these people compares well with samples from
      Chelechol ra Orrak. Last, archaeological, linguistic, and historical evidence
      demonstrates a great deal of cultural continuity in Palau through time as
      expected if the same population was inhabiting the archipelago. CONCLUSIONS:
      Prehistoric Palauan populations were normal sized and exhibit traits that fall
      within the normal variation for Homo sapiens-they do not support the claims by
      Berger et al. (2008) that there were smaller-bodied populations living in Palau
      or that insular dwarfism took place such as may be the case for Homo
      floresiensis.

PMID- 18728773
TI  - Rapid and reversible recruitment of early visual cortex for touch.
AB  - BACKGROUND: The loss of vision has been associated with enhanced performance in
      non-visual tasks such as tactile discrimination and sound localization. Current
      evidence suggests that these functional gains are linked to the recruitment of
      the occipital visual cortex for non-visual processing, but the neurophysiological
      mechanisms underlying these crossmodal changes remain uncertain. One possible
      explanation is that visual deprivation is associated with an unmasking of non
      visual input into visual cortex. METHODOLOGY/PRINCIPAL FINDINGS: We investigated
      the effect of sudden, complete and prolonged visual deprivation (five days) in
      normally sighted adult individuals while they were immersed in an intensive
      tactile training program. Following the five-day period, blindfolded subjects
      performed better on a Braille character discrimination task. In the blindfold
      group, serial fMRI scans revealed an increase in BOLD signal within the occipital
      cortex in response to tactile stimulation after five days of complete visual
      deprivation. This increase in signal was no longer present 24 hours after
      blindfold removal. Finally, reversible disruption of occipital cortex function on
      the fifth day (by repetitive transcranial magnetic stimulation; rTMS) impaired
      Braille character recognition ability in the blindfold group but not in non
      blindfolded controls. This disruptive effect was no longer evident once the
      blindfold had been removed for 24 hours. CONCLUSIONS/SIGNIFICANCE: Overall, our
      findings suggest that sudden and complete visual deprivation in normally sighted
      individuals can lead to profound, but rapidly reversible, neuroplastic changes by
      which the occipital cortex becomes engaged in processing of non-visual
      information. The speed and dynamic nature of the observed changes suggests that
      normally inhibited or masked functions in the sighted are revealed by visual
      loss. The unmasking of pre-existing connections and shifts in connectivity
      represent rapid, early plastic changes, which presumably can lead, if sustained
      and reinforced, to slower developing, but more permanent structural changes, such
      as the establishment of new neural connections in the blind.

PMID- 18728775
TI  - Evaluation of two methods to estimate and monitor bird populations.
AB  - BACKGROUND: Effective management depends upon accurately estimating trends in
      abundance of bird populations over time, and in some cases estimating abundance.
      Two population estimation methods, double observer (DO) and double sampling (DS),
      have been advocated for avian population studies and the relative merits and
      short-comings of these methods remain an area of debate. METHODOLOGY/PRINCIPAL
      FINDINGS: We used simulations to evaluate the performances of these two
      population estimation methods under a range of realistic scenarios. For three
      hypothetical populations with different levels of clustering, we generated DO and
      DS population size estimates for a range of detection probabilities and survey
      proportions. Population estimates for both methods were centered on the true
      population size for all levels of population clustering and survey proportions
      when detection probabilities were greater than 20%. The DO method underestimated
      the population at detection probabilities less than 30% whereas the DS method
      remained essentially unbiased. The coverage probability of 95% confidence
      intervals for population estimates was slightly less than the nominal level for
      the DS method but was substantially below the nominal level for the DO method at
      high detection probabilities. Differences in observer detection probabilities did
      not affect the accuracy and precision of population estimates of the DO method.
      Population estimates for the DS method remained unbiased as the proportion of
      units intensively surveyed changed, but the variance of the estimates decreased
      with increasing proportion intensively surveyed. CONCLUSIONS/SIGNIFICANCE: The DO
      and DS methods can be applied in many different settings and our evaluations
      provide important information on the performance of these two methods that can
      assist researchers in selecting the method most appropriate for their particular
      needs.

PMID- 18728776
TI  - Climate warming, marine protected areas and the ocean-scale integrity of coral
      reef ecosystems.
AB  - Coral reefs have emerged as one of the ecosystems most vulnerable to climate
      variation and change. While the contribution of a warming climate to the loss of
      live coral cover has been well documented across large spatial and temporal
      scales, the associated effects on fish have not. Here, we respond to recent and
      repeated calls to assess the importance of local management in conserving coral
      reefs in the context of global climate change. Such information is important, as
      coral reef fish assemblages are the most species dense vertebrate communities on
      earth, contributing critical ecosystem functions and providing crucial ecosystem
      services to human societies in tropical countries. Our assessment of the impacts
      of the 1998 mass bleaching event on coral cover, reef structural complexity, and
      reef associated fishes spans 7 countries, 66 sites and 26 degrees of latitude in
      the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size
      structure, diversity and trophic composition of the reef fish community have
      followed coral declines. Although the ocean scale integrity of these coral reef
      ecosystems has been lost, it is positive to see the effects are spatially
      variable at multiple scales, with impacts and vulnerability affected by geography
      but not management regime. Existing no-take marine protected areas still support
      high biomass of fish, however they had no positive affect on the ecosystem
      response to large-scale disturbance. This suggests a need for future conservation
      and management efforts to identify and protect regional refugia, which should be
      integrated into existing management frameworks and combined with policies to
      improve system-wide resilience to climate variation and change.

PMID- 18728777
TI  - Unusual repertoire of vocalizations in the BTBR T+tf/J mouse model of autism.
AB  - BTBR T+ tf/J (BTBR) is an inbred mouse strain that displays social abnormalities
      and repetitive behaviors analogous to the first and third diagnostic symptoms of
      autism. Here we investigate ultrasonic vocalizations in BTBR, to address the
      second diagnostic symptom of autism, communication deficits. As compared to the
      commonly used C57BL/6J (B6) strain, BTBR pups called more loudly and more
      frequently when separated from their mothers and siblings. Detailed analysis of
      ten categories of calls revealed an unusual pattern in BTBR as compared to B6.
      BTBR emitted high levels of harmonics, two-syllable, and composite calls, but
      minimal numbers of chevron-shaped syllables, upward, downward, and short calls.
      Because body weights were higher in BTBR than B6 pups, one possible explanation
      was that larger thoracic size was responsible for the louder calls and different
      distribution of syllable categories. To test this possibility, we recorded
      separation calls from FVB/NJ, a strain with body weights similar to BTBR, and
      129X1/SvJ, a strain with body weights similar to B6. BTBR remained the outlier on
      number of calls, displaying low numbers of complex, upward, chevron, short, and
      frequency steps calls, along with high harmonics and composites. Further,
      developmental milestones and growth rates were accelerated in BTBR, indicating an
      unusual neurodevelopmental trajectory. Overall, our findings demonstrate strain
      specific patterns of ultrasonic calls that may represent different lexicons, or
      innate variations in complex vocal repertoires, in genetically distinct strains
      of mice. Particularly intriguing is the unusual pattern of vocalizations and the
      more frequent, loud harmonics evident in the BTBR mouse model of autism that may
      resemble the atypical vocalizations seen in some autistic infants.

PMID- 18728778
TI  - Overexpression of partner of numb induces asymmetric distribution of the PI4P 5
      Kinase Skittles in mitotic sensory organ precursor cells in Drosophila.
AB  - Unequal segregation of cell fate determinants at mitosis is a conserved mechanism
      whereby cell fate diversity can be generated during development. In Drosophila,
      each sensory organ precursor cell (SOP) divides asymmetrically to produce an
      anterior pIIb and a posterior pIIa cell. The Par6-aPKC complex localizes at the
      posterior pole of dividing SOPs and directs the actin-dependent localization of
      the cell fate determinants Numb, Partner of Numb (Pon) and Neuralized at the
      opposite pole. The plasma membrane lipid phosphatidylinositol (4,5)-bisphosphate
      (PIP2) regulates the plasma membrane localization and activity of various
      proteins, including several actin regulators, thereby modulating actin-based
      processes. Here, we have examined the distribution of PIP2 and of the PIP2
      producing kinase Skittles (Sktl) in mitotic SOPs. Our analysis indicates that
      both Sktl and PIP2 reporters are uniformly distributed in mitotic SOPs. In the
      course of this study, we have observed that overexpression of full-length Pon or
      its localization domain (LD) fused to the Red Fluorescent Protein (RFP::Pon(LD))
      results in asymmetric distribution of Sktl and PIP2 reporters in dividing SOPs.
      Our observation that Pon overexpression alters polar protein distribution is
      relevant because RFP::Pon(LD) is often used as a polarity marker in dividing
      progenitors.

PMID- 18728779
TI  - Gender differences in the risk of HIV infection among persons reporting
      abstinence, monogamy, and multiple sexual partners in northern Tanzania.
AB  - BACKGROUND: Monogamy, together with abstinence, partner reduction, and condom
      use, is widely advocated as a key behavioral strategy to prevent HIV infection in
      sub-Saharan Africa. We examined the association between the number of sexual
      partners and the risk of HIV seropositivity among men and women presenting for
      HIV voluntary counseling and testing (VCT) in northern Tanzania. METHODOLOGY/
      PRINCIPAL FINDINGS: Clients presenting for HIV VCT at a community-based AIDS
      service organization in Moshi, Tanzania were surveyed between November 2003 and
      December 2007. Data on sociodemographic characteristics, reasons for testing,
      sexual behaviors, and symptoms were collected. Men and women were categorized by
      number of lifetime sexual partners, and rates of seropositivity were reported by
      category. Factors associated with HIV seropositivity among monogamous males and
      females were identified by a multivariate logistic regression model. Of 6,549
      clients, 3,607 (55%) were female, and the median age was 30 years (IQR 24-40).
      939 (25%) females and 293 (10%) males (p<0.0001) were HIV seropositive. Among
      1,244 (34%) monogamous females and 423 (14%) monogamous males, the risk of HIV
      infection was 19% and 4%, respectively (p<0.0001). The risk increased
      monotonically with additional partners up to 45% (p<0.001) and 15% (p<0.001) for
      women and men, respectively with 5 or more partners. In multivariate analysis,
      HIV seropositivity among monogamous women was most strongly associated with age
      (p<0.0001), lower education (p<0.004), and reporting a partner with other
      partners (p = 0.015). Only age was a significant risk factor for monogamous men
      (p = 0.0004). INTERPRETATION: Among women presenting for VCT, the number of
      partners is strongly associated with rates of seropositivity; however, even women
      reporting lifetime monogamy have a high risk for HIV infection. Partner reduction
      should be coupled with efforts to place tools in the hands of sexually active
      women to reduce their risk of contracting HIV.

PMID- 18728780
TI  - Adenine nucleotide translocator transports haem precursors into mitochondria.
AB  - Haem is a prosthetic group for haem proteins, which play an essential role in
      oxygen transport, respiration, signal transduction, and detoxification. In haem
      biosynthesis, the haem precursor protoporphyrin IX (PP IX) must be accumulated
      into the mitochondrial matrix across the inner membrane, but its mechanism is
      largely unclear. Here we show that adenine nucleotide translocator (ANT), the
      inner membrane transporter, contributes to haem biosynthesis by facilitating
      mitochondrial accumulation of its precursors. We identified that haem and PP IX
      specifically bind to ANT. Mitochondrial uptake of PP IX was inhibited by ADP, a
      known substrate of ANT. Conversely, ADP uptake into mitochondria was
      competitively inhibited by haem and its precursors, suggesting that haem-related
      porphyrins are accumulated into mitochondria via ANT. Furthermore, disruption of
      the ANT genes in yeast resulted in a reduction of haem biosynthesis by blocking
      the translocation of haem precursors into the matrix. Our results represent a new
      model that ANT plays a crucial role in haem biosynthesis by facilitating
      accumulation of its precursors into the mitochondrial matrix.

PMID- 18728781
TI  - Choice of cell-delivery route for skeletal myoblast transplantation for treating
      post-infarction chronic heart failure in rat.
AB  - BACKGROUND: Intramyocardial injection of skeletal myoblasts (SMB) has been shown
      to be a promising strategy for treating post-infarction chronic heart failure.
      However, insufficient therapeutic benefit and occurrence of ventricular
      arrhythmias are concerns. We hypothesised that the use of a retrograde
      intracoronary route for SMB-delivery might favourably alter the behaviour of the
      grafted SMB, consequently modulating the therapeutic effects and
      arrhythmogenicity. METHODS AND RESULTS: Three weeks after coronary artery
      ligation in female wild-type rats, 5x10(6) GFP-expressing SMB or PBS only
      (control) were injected via either the intramyocardial or retrograde
      intracoronary routes. Injection of SMB via either route similarly improved
      cardiac performance and physical activity, associated with reduced cardiomyocyte
      hypertrophy and fibrosis. Grafted SMB via either route were only present in low
      numbers in the myocardium, analysed by real-time PCR for the Y-chromosome
      specific gene, Sry. Cardiomyogenic differentiation of grafted SMB was extremely
      rare. Continuous ECG monitoring by telemetry revealed that only intramyocardial
      injection of SMB produced spontaneous ventricular tachycardia up to 14 days,
      associated with local myocardial heterogeneity generated by clusters of injected
      SMB and accumulated inflammatory cells. A small number of ventricular premature
      contractions with latent ventricular tachycardia were detected in the late-phase
      of SMB injection regardless of the injection-route. CONCLUSION: Retrograde
      intracoronary injection of SMB provided significant therapeutic benefits with
      attenuated early-phase arrhythmogenicity in treating ischaemic cardiomyopathy,
      indicating the promising utility of this route for SMB-delivery. Late-phase
      arrhythmogenicity remains a concern, regardless of the delivery route.

PMID- 18728782
TI  - Genetic architecture of hybrid male sterility in Drosophila: analysis of
      intraspecies variation for interspecies isolation.
AB  - BACKGROUND: The genetic basis of postzygotic isolation is a central puzzle in
      evolutionary biology. Evolutionary forces causing hybrid sterility or inviability
      act on the responsible genes while they still are polymorphic, thus we have to
      study these traits as they arise, before isolation is complete.
      METHODOLOGY/PRINCIPAL FINDINGS: Isofemale strains of D. mojavensis vary
      significantly in their production of sterile F(1) sons when females are crossed
      to D. arizonae males. We took advantage of the intraspecific polymorphism, in a
      novel design, to perform quantitative trait locus (QTL) mapping analyses directly
      on F(1) hybrid male sterility itself. We found that the genetic architecture of
      the polymorphism for hybrid male sterility (HMS) in the F(1) is complex,
      involving multiple QTL, epistasis, and cytoplasmic effects.
      CONCLUSIONS/SIGNIFICANCE: The role of extensive intraspecific polymorphism,
      multiple QTL, and epistatic interactions in HMS in this young species pair shows
      that HMS is arising as a complex trait in this system. Directional selection
      alone would be unlikely to maintain polymorphism at multiple loci, thus we
      hypothesize that directional selection is unlikely to be the only evolutionary
      force influencing postzygotic isolation.

PMID- 18728783
TI  - FGF2 translationally induced by hypoxia is involved in negative and positive
      feedback loops with HIF-1alpha.
AB  - BACKGROUND: Fibroblast growth factor 2 (FGF2) is a major angiogenic factor
      involved in angiogenesis and arteriogenesis, however the regulation of its
      expression during these processes is poorly documented. FGF2 mRNA contains an
      internal ribosome entry site (IRES), a translational regulator expected to allow
      mRNA expression during cellular stress. METHODOLOGY/PRINCIPAL FINDINGS: In the
      present study, we have developed a skin ischemia model in transgenic mice
      expressing a reporter transgene under the control of the FGF2 IRES. The results
      reveal that FGF2 is induced at the protein level during ischemia, concomitant
      with HIF-1alpha induction and a decrease in FGF2 mRNA. In addition, the FGF2 IRES
      is strongly activated under these ischemic conditions associated with hypoxia,
      whereas cap-dependent translation is repressed by 4E-BP hypophosphorylation. We
      also show that up-regulation of FGF2 protein expression in response to hypoxia
      correlates with the increase of FGF2 IRES activity in vitro, in human
      retinoblasts 911. The use of siRNAs targeting HIF or FGF2 indicates that FGF2 and
      HIF-1alpha reciprocally regulate their expression/accumulation, by a negative
      feedback loop in early hypoxia, followed by a positive feedback loop in late
      hypoxia. CONCLUSION/SIGNIFICANCE: FGF2 expression is up-regulated in vivo and in
      vitro in response to hypoxia. Strikingly, this up-regulation is not
      transcriptional. It seems to occur by an IRES-dependent mechanism, revealing new
      mechanistic aspects of the hypoxic response. In addition, our data show that FGF2
      interacts with HIF-1alpha in a unique crosstalk, with distinct stages in early
      and late hypoxia. These data reveal the physiological importance of IRES
      dependent translation during hypoxic stress and underline the complexity of the
      cellular response to hypoxia, suggesting a novel role of FGF2 in the regulation
      of HIF-1alpha during the induction of angiogenesis.

PMID- 18728784
TI  - Synthetic activation of endogenous PI3K and Rac identifies an AND-gate switch for
      cell polarization and migration.
AB  - Phosphatidylinositol 3-OH kinase (PI3K) has been widely studied as a principal
      regulator of cell polarization, migration, and chemotaxis. Surprisingly, recent
      studies showed that mammalian neutrophils and Dictyostelium discoideum cells can
      polarize and migrate in the absence of PI3K activity. Here we directly probe the
      roles of PI3K and its downstream effector, Rac, in HL-60 neutrophils by using a
      chemical biology approach whereby the endogenously present enzymes are
      synthetically activated in less than one minute. We show that uniform activation
      of endogenous PI3K is sufficient to polarize previously unpolarized neutrophils
      and trigger effective cell migration. After a delay following symmetrical
      phosphatidylinositol (3,4,5)-triphosphate (PIP(3)) production, a polarized
      distribution of PIP(3) was induced by positive feedback requiring actin
      polymerization. Pharmacological studies argue that this process does not require
      receptor-coupled trimeric G proteins. Contrary to the current working model,
      rapid activation of endogenous Rac proteins triggered effective actin
      polymerization but failed to feed back to PI3K to generate PIP(3) or induce cell
      polarization. Thus, the increase in PIP(3) concentration at the leading edge is
      generated by positive feedback with an AND gate logic with a PI3K-Rac-actin
      polymerization pathway as a first input and a PI3K initiated non-Rac pathway as a
      second input. This AND-gate control for cell polarization can explain how Rac can
      be employed for both PI3K-dependent and -independent signaling pathways
      coexisting in the same cell.

PMID- 18728786
TI  - Random drift versus selection in academic vocabulary: an evolutionary analysis of
      published keywords.
AB  - The evolution of vocabulary in academic publishing is characterized via keyword
      frequencies recorded in the ISI Web of Science citations database. In four
      distinct case-studies, evolutionary analysis of keyword frequency change through
      time is compared to a model of random copying used as the null hypothesis, such
      that selection may be identified against it. The case studies from the physical
      sciences indicate greater selection in keyword choice than in the social
      sciences. Similar evolutionary analyses can be applied to a wide range of
      phenomena; wherever the popularity of multiple items through time has been
      recorded, as with web searches, or sales of popular music and books, for example.

PMID- 18728785
TI  - Muscles in "concert": study of primary motor cortex upper limb functional
      topography.
AB  - BACKGROUND: Previous studies with Transcranial Magnetic Stimulation (TMS) have
      focused on the cortical representation of limited group of muscles. No attempts
      have been carried out so far to get simultaneous recordings from hand, forearm
      and arm with TMS in order to disentangle a 'functional' map providing information
      on the rules orchestrating muscle coupling and overlap. The aim of the present
      study is to disentangle functional associations between 12 upper limb muscles
      using two measures: cortical overlapping and cortical covariation of each pair of
      muscles. Interhemispheric differences and the influence of posture were evaluated
      as well. METHODOLOGY/PRINCIPAL FINDINGS: TMS mapping studies of 12 muscles
      belonging to hand, forearm and arm were performed. Findings demonstrate
      significant differences between the 66 pairs of muscles in terms of cortical
      overlapping: extremely high for hand-forearm muscles and very low for arm vs
      hand/forearm muscles. When right and left hemispheres were compared, overlapping
      between all possible pairs of muscles in the left hemisphere (62.5%) was
      significantly higher than in the right one (53.5% ). The arm/hand posture
      influenced both measures of cortical association, the effect of Position being
      significant [p = .021] on overlapping, resulting in 59.5% with prone vs 53.2%
      with supine hand, but only for pairs of muscles belonging to hand and forearm,
      while no changes occurred in the overlapping of proximal muscles with those of
      more distal districts. CONCLUSIONS/SIGNIFICANCE: Larger overlapping in the left
      hemisphere could be related to its lifetime higher training of all twelve muscles
      studied with respect to the right hemisphere, resulting in larger intra-cortical
      connectivity within primary motor cortex. Altogether, findings with prone hand
      might be ascribed to mechanisms facilitating coupling of muscles for object
      grasping and lifting -with more proximal involvement for joint stabilization-
      compared to supine hand facilitating actions like catching. TMS multiple-muscle
      mapping studies permit a better understanding of motor control and 'plastic'
      reorganization of motor system.

PMID- 18728787
TI  - Bi-directional sexual dimorphisms of the song control nucleus HVC in a songbird
      with unison song.
AB  - Sexually dimorphic anatomy of brain areas is thought to be causally linked to sex
      differences in behaviour and cognitive functions. The sex with the regional size
      advantage (male or female) differs between brain areas and species. Among adult
      songbirds, males have larger brain areas such as the HVC (proper name) and RA
      (robust nucleus of the arcopallium) that control the production of learned songs.
      Forest weavers (Ploceus bicolor) mated pairs sing a unison duet in which male and
      female mates learn to produce identical songs. We show with histological
      techniques that the volume and neuron numbers of HVC and RA were > or =1.5 times
      larger in males than in females despite their identical songs. In contrast, using
      in-situ hybridizations, females have much higher (30-70%) expression levels of
      mRNA of a number of synapse-related proteins in HVC and/or RA than their male
      counterparts. Male-typical and female-typical sexual differentiation appears to
      act on different aspects of the phenotypes within the same brain areas, leading
      females and males to produce the same behaviour using different cellular
      mechanisms.

PMID- 18728788
TI  - Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and
      metastatic properties.
AB  - BACKGROUND: Cancer stem cells (CSCs) are thought to be responsible for tumor
      regeneration after chemotherapy, although direct confirmation of this remains
      forthcoming. We therefore investigated whether drug treatment could enrich and
      maintain CSCs and whether the high tumorogenic and metastatic abilities of CSCs
      were based on their marked ability to produce growth and angiogenic factors and
      express their cognate receptors to stimulate tumor cell proliferation and stroma
      formation. METHODOLOGY/FINDINGS: Treatment of lung tumor cells with doxorubicin,
      cisplatin, or etoposide resulted in the selection of drug surviving cells (DSCs).
      These cells expressed CD133, CD117, SSEA-3, TRA1-81, Oct-4, and nuclear beta
      catenin and lost expression of the differentiation markers cytokeratins 8/18 (CK
      8/18). DSCs were able to grow as tumor spheres, maintain self-renewal capacity,
      and differentiate. Differentiated progenitors lost expression of CD133, gained CK
      8/18 and acquired drug sensitivity. In the presence of drugs, differentiation of
      DSCs was abrogated allowing propagation of cells with CSC-like characteristics.
      Lung DSCs demonstrated high tumorogenic and metastatic potential following
      inoculation into SCID mice, which supported their classification as CSCs. Luminex
      analysis of human and murine cytokines in sonicated lysates of parental- and CSC
      derived tumors revealed that CSC-derived tumors contained two- to three-fold
      higher levels of human angiogenic and growth factors (VEGF, bFGF, IL-6, IL-8,
      HGF, PDGF-BB, G-CSF, and SCGF-beta). CSCs also showed elevated levels of
      expression of human VEGFR2, FGFR2, CXCR1, 2 and 4 receptors. Moreover, human CSCs
      growing in SCID mice stimulated murine stroma to produce elevated levels of
      angiogenic and growth factors. CONCLUSIONS/SIGNIFICANCE: These findings suggest
      that chemotherapy can lead to propagation of CSCs and prevention of their
      differentiation. The high tumorigenic and metastatic potentials of CSCs are
      associated with efficient cytokine network production that may represent a target
      for increased efficacy of cancer therapy.

PMID- 18728789
TI  - Apoptosis in the trabecular meshwork of glaucomatous patients.
AB  - We established and validated an in toto method to perform TdT-mediated dUTP nick
      end labeling to study apoptosis in human trabecular meshwork tissue obtained
      during trabeculectomy in glaucoma patients. In specimens from patients with
      primary open-angle glaucoma and primary angle-closure glaucoma, we detected a
      tendency for more apoptotic cells to accumulate in patients with primary open
      angle glaucoma. The utility of this method to study apoptosis in the trabecular
      meshwork is discussed, as well as its application as a tool in biologic samples.

PMID- 18728790
TI  - A novel phenotype-genotype relationship with a TGFBI exon 14 mutation in a
      pedigree with a unique corneal dystrophy of Bowman's layer.
AB  - PURPOSE: Corneal dystrophy of Bowman's layer (CDB) belongs to a group of
      dystrophies associated with mutations in the transforming growth factor-beta
      induced (TGFBI) gene. CDB is further divided into a geographic variant (CDB1/Reis
      Bucklers, RBCD), and a honeycomb variant (CDB2/Thiel Behnke, TBCD). We undertook
      mutational analysis of TGFBI in a family with an unusual CDB variant and describe
      a novel phenotype-genotype association. METHODS: Individuals from a pedigree with
      CDB underwent extensive phenotyping, including laser scanning in vivo confocal
      microscopy, and histological examination of four corneal buttons obtained at
      penetrating keratoplasty. Transmission electron microscopy of an excised
      allograft cornea from one affected individual was also performed. Following
      informed consent, DNA samples were collected. Polymerase chain reaction (PCR) and
      sequencing of all coding exons of TGFBI was performed. Family members were
      recruited with subsequent phenotyping and genotyping, and paternity testing.
      RESULTS: Clinical examination and other phenotypic information confirmed a
      diagnosis of CDB, with various features either more suggestive of CDB1 or of
      CDB2. A mutation in exon 14, H626P, segregated with the disease in this pedigree.
      This mutation was confirmed with NlaIII restriction enzyme digest, and was not
      seen in 100 control chromosomes. CONCLUSIONS: Within this pedigree, CDB
      segregates with an H626P mutation, which is previously described occurring in
      lattice corneal dystrophy. The majority of mutations in TGFBI previously
      described segregating with CDB1 and CDB2 are R124L and R555Q, respectively.
      Although a Bowman's layer dystrophy, the phenotype in this pedigree does not
      closely conform to the classical diagnostic criteria for either CDB1 or CDB2, and
      therefore represents a novel phenotype-genotype correlation.

PMID- 18728791
TI  - Prolonged cholinergic enrichment influences regional cortical activation in early
      Alzheimer's disease.
AB  - Neuroimaging studies of cholinesterase inhibitor (ChEI) treatment in Alzheimer's
      disease (AD) indicate that the short and long term actions of ChEIs are
      dissimilar. fMRI studies of the ChEI rivastigmine have focused on its short term
      action. In this exploratory study the effect of prolonged (20 weeks) rivastigmine
      treatment on regional brain activity was measured with fMRI in patients with mild
      AD. Eleven patients with probable AD and nine age-matched controls were assessed
      with a Pyramids and Palm Trees semantic association and an n-back working memory
      fMRI paradigm. In the patient group only, the assessment was repeated after 20
      weeks of treatment. There was an increase in task-related brain activity after
      treatment with activations more like those of normal healthy elderly.
      Behaviorally, however, there were no significant differences between baseline and
      retest scores, with a range of performance probably reflecting variation in drug
      efficacy across patients. Variable patient response and drug dynamic/kinetic
      factors in small patient groups will inevitably bias (either way) the effect size
      of any relevant drug related changes in activation. Future studies should take
      drug response into account to provide more insight into the benefits of ChEI
      drugs at the individual level.

PMID- 18728792
TI  - Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans.
AB  - BACKGROUND AND PURPOSE: Cerebral ischemia is a common, morbid condition
      accompanied by cognitive decline. Recent reports on the vascular health benefits
      of flavanol-containing foods signify a promising approach to the treatment of
      cerebral ischemia. Our study was designed to investigate the effects of flavanol
      rich cocoa (FRC) consumption on cerebral blood flow in older healthy volunteers.
      METHODS: We used transcranial Doppler (TCD) ultrasound to measure mean blood flow
      velocity (MFV) in the middle cerebral artery (MCA) in thirty-four healthy elderly
      volunteers (72 +/- 6 years) in response to the regular intake of FRC or flavanol
      poor cocoa (FPC). RESULTS: In response to two weeks of FRC intake, MFV increased
      by 8% +/- 4% at one week (p = 0.01) and 10% +/- 4% (p = 0.04) at two weeks. In
      response to one week of cocoa, significantly more subjects in the FRC as compared
      with the FPC group had an increase in their MFV (p < 0.05). CONCLUSIONS: In
      summary, we show that dietary intake of FRC is associated with a significant
      increase in cerebral blood flow velocity in the MCA as measured by TCD. Our data
      suggest a promising role for regular cocoa flavanol's consumption in the
      treatment of cerebrovascular ischemic syndromes, including dementias and stroke.

PMID- 18728793
TI  - The development of behavioral and endocrine abnormalities in rats after repeated
      exposure to direct and indirect stress.
AB  - The present study compared the effects of direct and indirect stress on the
      behavior and hypothalamic-pituitary-adrenal axis of rats. Animals were placed in
      a two compartment box. In one compartment the direct stressed rat was subjected
      to electric foot shocks randomly applied for 10 minutes (0.5 mA of 1 s duration).
      In the adjacent compartment, the indirect stressed rats witnessed the application
      of these electric foot shocks. Our data showed substantial behavioral changes in
      the open field test, but limited effects in the elevated plus maze. The findings
      suggested that single and repeated stress exposure may have different
      consequences, that the effects of stress exposure may develop over time and
      persist for an extended period, and that both direct and indirect stressed rats
      displayed a hyposensitive HPA axis following acute restraint stress. Overall our
      observations moderately indicate direct exposure to elicit behavioral changes,
      and both direct and indirect exposure to stress to result in aberrations within
      the neuroendocrine system. With additional development our stress models may be
      considered for studying the complex interrelationship between an external
      stressor, and the experience of the organism.

PMID- 18728794
TI  - Effect of 17beta-estradiol on olfactory bulbectomy-induced oxidative stress and
      behavioral changes in rats.
AB  - The present study evaluated 17beta-estradiol (17betaE(2)) (2.5 mg/kg sc) effects
      on bilateral OBX-induced behavioral changes and oxidative stress. OBX in male
      Wistar rats produced an increase in lipid peroxidation products and a decline in
      reduced glutathione (GSH) content and glutathione peroxidase (GSH-Px) activity,
      together with an increase in caspase-3 activity. Additionally, OBX triggered
      changes of behavior such as an enhancement of immobility time in the forced swim
      test and hyperactivity in the open field test. These changes were reversed by
      treatment with 17betaE(2) (14 days). Our results reveled that 17betaE(2) has a
      protective effect against oxidative stress, cell damage and behavioral changes
      induced by OBX, and present antidepressant and antianxiety properties.

PMID- 18728795
TI  - Drug and alcohol misuse in first episode psychosis: An observational study.
AB  - BACKGROUND: There have been very few observational studies of drug and alcohol
      misuse in first-episode psychosis in the UK. METHOD: Using an observational
      database of first episode psychosis in Northumberland, a county in Northern
      England, information on patients aged 16 to 36 years were collected at
      presentation and annual follow-up between October 1998 and October 2005. Patterns
      of drug and alcohol misuse were compared using hospitalization as an outcome
      measure, and violence rates were examined retrospectively. RESULTS: Drug misuse
      without alcohol misuse was associated with a highly significant increase in
      hospital days. An alcohol problem, either with or without coexisting drug misuse,
      was not predictive of increased hospital days. Drug and alcohol misuse together
      was associated with violence. CONCLUSIONS: This paper lends some support to those
      Early Intervention in Psychosis (EIP) teams currently advising patients that drug
      misuse may have a greater impact than alcohol use on the outcome of first-episode
      psychosis.

PMID- 18728796
TI  - Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2
      (COX2) inhibitor, in the management of pain and osteoarthritis.
AB  - Lumiracoxib is a COX2 inhibitor that is highly selective, is more effective than
      placebo on pain in osteoarthritis (OA), with similar analgesic and anti
      inflammatory effects as non-selective NSAIDs and the selective COX2 inhibitor
      celecoxib, has a lower incidence of upper gastrointestinal (GI) side effects in
      patients not taking aspirin, and a similar incidence of cardiovascular (CV) side
      effects compared to naproxen or ibuprofen. In the context of earlier guidelines
      and taking into account the GI and CV safety results of the TARGET study,
      lumiracoxib had secured European Medicines Agency (EMEA) approval with as
      indication symptomatic treatment of OA as well as short-term management of acute
      pain associated with primary dysmenorrhea and following orthopedic or dental
      surgery. In the complex clinical context of efficiency and safety of selective
      and non-selective COX inhibitors, its prescription and use should be based on the
      risk and safety profile of the patient. In addition, there is further need for
      long-term GI and CV safety studies and general post-marketing safety on its use
      in daily practice. Meanwhile, at the time of submission of this manuscript, the
      EMEA has withdrawn lumiracoxib throughout Europe because of the risk of serious
      side effects affecting the liver.

PMID- 18728797
TI  - Serum substance P levels in patients with chronic schizophrenia treated with
      typical or atypical antipsychotics.
AB  - Aspiration pneumonia is a major cause of death in patients with dysphagia, often
      accompanied by psychiatric symptoms. The inhibition of swallowing and cough
      reflexes, which contribute to a significant risk for aspiration, may be related
      to decreased levels of substance P. Clinical studies indicate a strong
      association of an increased mortality in psychiatric patients with the use of
      antipsychotics. The present study documented fewer positive episodes of
      swallowing reflex in patients treated with haloperidol for schizophrenia (7/11;
      63.6%) than those treated with risperidone (10/11; 90.9%). In addition, patients
      treated with risperidone had serum substance P levels comparable with control
      subjects (29.0 +/- 7.8 pg/mL, 29.6 +/- 7.6, respectively; p = 0.9), while
      patients treated with haloperidol had significantly lower serum substance P
      levels (20.6 +/- 5.5 pg/mL; p < 0.01). Among patients on haloperidol, those with
      negative episodes of reflex (4/11; 36.4%) had serum substance P levels at 15.8 +/
      1.0 pg/mL, in contrast with those with positive episodes (7/11; 63.6%) who had
      serum levels at 23.4 +/- 4.9 pg/mL. However, in the patient group treated with
      risperidone, serum substance P levels in the majority of patients with positive
      episodes of reflexes (10/11, 90.9%; 30.1 +/- 7.2 pg/mL) was found to be as high
      as in control subjects, all with positive episodes (5/5, 100%; 29.6 +/- 7.6
      pg/mL) (p = 0.866), and higher than in one patient with negative reflex (1/11,
      9.1%; 18.0 +/- 0.0 pg/mL). These results suggest that the decreased serum
      substance P levels are strongly associated with the use of haloperidol, as well
      as decreased swallowing reflexes. This suggests that serum substance P levels may
      be a useful predictive marker for the increased risk of developing aspiration, or
      subsequently aspiration pneumonia. Moreover, this increased incidence of
      aspiration may contribute to an increased mortality in patients following
      antipsychotic therapy. Risperidone, which has little influence on serum substance
      P productions, may be a more appropriate first-line drug of choice for treatment
      of schizophrenia.

PMID- 18728798
TI  - Preliminary effects of pagoclone, a partial GABA(A) agonist, on
      neuropsychological performance.
AB  - Pagoclone is a novel cyclopyrrolone that acts as a partial GABA(A) receptor
      agonist. Preclinical studies suggest that pagoclone may have clinical utility as
      an anxiolytic agent, as well as a reduced incidence of side-effects. The present
      study was conducted to determine whether pagoclone would affect healthy
      individuals' performances on neuropsychological measures as a function of dose
      within the projected therapeutic range. Twelve healthy adult subjects were
      randomly assigned to dosage groups in a 3-way crossover study. Participants were
      administered neuropsychological measures six hours following dosing on Day 1 and
      Day 6 of administration of the drug. Dose effects were noted on measures of
      alertness, learning, and memory and movement time. Significant effects were also
      noted on measures of alertness, learning and memory, information processing and
      psychomotor speed. Overall, the results of this small, preliminary study do not
      support a finding of behavioral toxicity for these doses of pagoclone. Rather, a
      pattern was found of transient and mild negative effects on learning and memory
      scores at the highest dose administered, though these changes were small and no
      longer evident by the sixth day of use.

PMID- 18728799
TI  - Risperidone treatment for ADHD in children and adolescents with bipolar disorder.
AB  - OBJECTIVE: Children and adolescents with bipolar disorder are also at high risk
      of having comorbid attention-deficit hyperactivity disorder (ADHD). The objective
      of this study was to estimate improvement in ADHD symptoms in children with
      bipolar disorder. METHODS: This was an open-label, study of risperidone
      monotherapy for the treatment of pediatric bipolar disorder. Thirty-one children
      and adolescents 4-15 years of age (7.2 +/- 2.8 years) of both sexes (71%, N = 22
      male) with pediatric bipolar disorder (YMRS score = 32.9 +/- 8.8) and ADHD (ADHD
      RS score = 37.9 +/- 8.9) were included in these analyses. RESULTS: Improvement in
      ADHD symptoms was contingent on improvement in manic symptoms. Although both
      hyperactive/impulsive (-7.5 +/- 5.5.6, p < 0.05) and inattentive (-6.8 +/- 5.0, p
      < 0.05) ADHD symptoms were significantly improved with risperidone, improvement
      was modest, and only 29% of subjects (N = 6) showed a 30% reduction in ADHD
      rating scale scores and had a CGI-I </= 2. CONCLUSIONS: These results suggest
      that that treatment with risperidone is associated with tangible but generally
      modest improvement of symptoms of ADHD in children with bipolar disorder.

PMID- 18728800
TI  - Drugs for Parkinson's disease: levodopa is still the gold standard.

PMID- 18728801
TI  - Differential diagnoses and management strategies in patients with schizophrenia
      and bipolar disorder.
AB  - Successful treatment of psychiatric disorders, including bipolar disorder and
      schizophrenia, is complicated and is affected by a broad range of factors
      associated with the diagnosis, choice of treatment and social factors. In these
      patients, treatment management must focus on accurate and early diagnosis, to
      ensure that correct treatment is administered as soon as possible. In both
      disorders, the treatment of the disease in the acute phase must be maintained
      long term to provide continuous relief and normal function; the treatment choice
      in the early stages of the disease may impact on long-term outcomes. In
      schizophrenia, treatment non-compliance is an important issue, with up to 50% of
      patients discontinuing treatment for reasons as diverse as efficacy failure,
      social barriers, and more commonly, adverse events. Treatment non-compliance also
      remains an issue in bipolar disorder, as tolerability of mood stabilizers,
      especially lithium, is not always good, and combination treatments are frequent.
      In order to achieve an optimal outcome in which the patient continues with their
      medication life-long, treatment should be tailored to each individual, taking
      into account treatment and family history, and balancing efficacy with
      tolerability to maximize patient benefit and minimize the risk of
      discontinuation. These case studies illustrate how treatment should be monitored,
      tailored and often changed over time to meet these needs.

PMID- 18728802
TI  - Anticonvulsant treatments of dysphoric mania: a trial of gabapentin, lamotrigine
      and carbamazepine in Iran.
AB  - The treatment of dysphoric mania is challenging given the need to treat symptoms
      of both depression and mania simultaneously without provoking any clinical
      exacerbation. The newer antiepileptic drugs such as gabapentin, lamotrogine, and
      carbamazepine are often used as adjuncts to either lithium or valproic acid in
      the treatment of bipolar disorder. We decided to undertake a monotherapy trial
      because previous evidence suggested mixed states may be more responsive to
      anticonvulsants than more traditional antimanic agents. 51 patients with a DSM IV
      diagnosis of dysphoric mania were randomized to three groups comprising
      gapbapentin, lamotrogine or carbamazepine and followed for 8 weeks. Psychiatric
      diagnosis was verified by the structural clinical interview for the DSM-IV
      (SCID). The MMPI-2 in full was used to assess symptoms at baseline and 8 weeks.
      All three groups showed significant changes in MMPI-2 scores for depression and
      mania subscales. Gabapentin showed the greatest change in depression symptom
      improvement relative to lamotrogine and carbamazepine, respectively. Although
      manic symptoms improved overall, here were no differences between groups in the
      degree of manic symptom improvement.

PMID- 18728803
TI  - First true initial ictal SPECT in partial epilepsy verified by
      electroencephalography.
AB  - Drug-resistant epilepsy can sometimes be treated by surgery. In these cases, an
      accurate identification of the epileptogenic area must be addressed before
      resection. Ictal SPECT is one of the presurgical evaluations that can be
      performed, but usually, the increase in the regional cerebral perfusion observed
      is produced by diffusion of ictal activity. Here we describe a patient studied
      with v-EEG and foramen ovale electrodes that suffered a seizure after intravenous
      infusion of etomidate. The sequence of etomidate administration, followed by
      radiotracer and seizure was good enough for us to suspect that a true initial
      ictal SPECT was observed. We have implemented a kinetic model with four
      compartments, previously described (Andersen 1989), in order to estimate the
      fraction of hydrophilic radiotracer in the brain during the pre-ictal and ictal
      periods. This model has shown that the fraction of hydrophilic radiotracer during
      the seizure into the brain would be between 18.9% and 42.3% of total infused. We
      show the first true initial ictal SPECT demonstrated by bioelectrical recordings
      of the brain activity, obtained by a correct succession of events and compatible
      with theoretical data obtained from the kinetic model.

PMID- 18728804
TI  - Review of risperidone for the treatment of pediatric and adolescent bipolar
      disorder and schizophrenia.
AB  - Risperidone is a commonly used medication for the treatment of bipolar disorder
      and schizophrenia in children and adolescents. It has been studied as a
      monotherapy treatment in early onset schizophrenia and as both monotherapy and
      combination therapy for pediatric bipolar disorder. Studies to date indicate that
      risperidone is an effective treatment for positive and negative symptoms of
      schizophrenia and mania symptoms of bipolar disorder. In young patient
      populations, side effects such as weight gain, extrapyramidal side effects, and
      prolactin elevation require consideration when evaluating the risk benefit ratio
      for individual patients. Here we review published studies of risperidone for the
      treatment of bipolar disorder and schizophrenia in children and adolescents to
      provide practitioners with an overview of published data on the efficacy and
      safety of risperidone in these patient populations.

PMID- 18728805
TI  - Epidemiology and treatment of post-stroke depression.
AB  - Mood depression is a common and serious complication after stroke. According to
      epidemiological studies, nearly 30% of stroke patients develop depression, either
      in the early or in the late stages after stroke. Although depression may affect
      functional recovery and quality of life after stroke, such condition is often
      ignored. In fact, only a minority of patients is diagnosed and even fewer are
      treated in the common clinical practice. Moreover, the real benefits of
      antidepressant (AD) therapy in post-stroke depression have not been fully
      clarified. In fact, controlled studies on the effectiveness of ADs in post stroke
      depression (PSD) are relatively few. Today, data available suggest that ADs may
      be generally effective in improving mood, but guidelines for the optimal
      treatment and its length are still lacking.

PMID- 18728806
TI  - Neurosteroids block the increase in intracellular calcium level induced by
      Alzheimer's beta-amyloid protein in long-term cultured rat hippocampal neurons.
AB  - The neurotoxicity of beta-amyloid protein (AbetaP) is implicated in the etiology
      of Alzheimer's disease. We previously have demonstrated that AbetaP forms Ca(2+)
      permeable pores on neuronal membranes, causes a marked increase in intracellular
      calcium level, and leads to neuronal death. Here, we investigated in detail the
      features of AbetaP-induced changes in intracellular Ca(2+) level in primary
      cultured rat hippocampal neurons using a multisite Ca(2+)-imaging system with
      fura-2 as a fluorescent probe. Only a small fraction of short-term cultured
      hippocampal neurons (ca 1 week in vitro) exhibited changes in intracellular
      Ca(2+) level after AbetaP exposure. However, AbetaP caused an acute increase in
      intracellular Ca(2+) level in long-term cultured neurons (ca 1 month in vitro).
      The responses to AbetaP were highly heterogeneous, and immunohistochemical
      analysis using an antibody to AbetaP revealed that AbetaP is deposited on some
      but not all neurons. Considering that the disruption of Ca(2+) homeostasis is the
      primary event in AbetaP neurotoxicity, substances that protect neurons from an
      AbetaP-induced intracellular Ca(2+) level increase may be candidates as
      therapeutic drugs for Alzheimer's disease. In line with the search for such
      protective substances, we found that the preadministration of neurosteroids
      including dehydroepiandrosterone, dehydroepiandrosterone sulfate, and
      pregnenolone significantly inhibits the increase in intracellular calcium level
      induced by AbetaP. Our results suggest the possible significance of
      neurosteroids, whose levels are reduced in the elderly, in preventing AbetaP
      neurotoxicity.

PMID- 18728807
TI  - Suicide risk in depression and bipolar disorder: Do impulsiveness-aggressiveness
      and pharmacotherapy predict suicidal intent?
AB  - The aims of the present study were to examine clinical, personality, and
      sociodemographic predictors of suicide risk in a sample of inpatients affected by
      major affective disorders. The participants were 74 inpatients affected by major
      depressive disorder or bipolar disorder-I. Patients completed a semi-structured
      interview, the Beck Hopelessness Scale, the Aggression Questionnaire, the Barratt
      Impulsiveness Scale, and the Hamilton scales for depression and anxiety. Over 52%
      of the patients were high suicide risks. Those at risk reported more severe
      depressive-anxious symptomatology, more impulsivity and more hostility.
      Impulsivity, the use of antidepressants, anxiety/somatization, and the use of
      mood stabilizers (a negative predictor) resulted in accurate predicting of
      suicide intent. Impulsivity and antidepressant use were the strongest predictors
      even after controlling for several sociodemographic and clinical variables.

PMID- 18728808
TI  - A review of ramelteon in the treatment of sleep disorders.
AB  - Ramelteon is a selective melatonin receptor (MT(1) and MT(2)) agonist that has
      been approved by the US Food and Drug Administration for the treatment of
      insomnia characterized by difficulty with sleep onset. It is the only approved
      sleep-promoting medication that does not have a direct sedating effect, but
      rather enhances sleep through effects on sleep regulatory mechanisms within the
      suprachiasmatic nucleus. Ramelteon has been shown to have no abuse liability and
      therefore is not scheduled by the U.S. Drug Enforcement Agency as a controlled
      substance. It is available as an 8 mg tablet, which should be taken approximately
      30 minutes prior to bedtime. The FDA approval contains no limitation on how long
      the medication may be prescribed.

PMID- 18728809
TI  - Association analysis between variants of the interleukin-1beta and the
      interleukin-1 receptor antagonist gene and antidepressant treatment response in
      major depression.
AB  - This study investigated the possible association of the interleukin-1 beta (IL
      1beta) C-511T promoter polymorphism and the interleukin-1 receptor antagonist (IL
      1Ra) (86bp)(n) variable number of tandem repeats (VNTR) polymorphism with
      antidepressant response to paroxetine and mirtazapine treatment. The study group
      consisted of 101 patients suffering from DSM-IV major depression participating in
      a randomized double-blind controlled clinical trial. Patients homozygous for the
      IL-1beta-511T allele had a significantly faster and more pronounced response to
      paroxetine treatment than IL-1beta-511C allele carriers. No association was found
      for the IL-1beta C-511T polymorphism with mirtazapine treatment response. The IL
      1Ra VNTR showed neither an association with paroxetine nor with mirtazapine
      treatment response. Our results provide further suggestive evidence that time
      course of response and antidepressant efficacy of paroxetine, but not of
      mirtazapine, is influenced in a clinically relevant manner by the IL-1beta C-511T
      gene variant. Our data do not support the hypothesis that the IL-1Ra (86bp)(n)
      VNTR affects antidepressant treatment response to paroxetine or mirtazapine. An
      independent replication of our finding is needed. If replicated, the IL-1beta C
      511T promoter polymorphism could be considered useful for prospective
      confirmatory pharmacogenetic trials in patients with major depression.

PMID- 18728810
TI  - Normal pressure hydrocephalus co-existing with a second dementia disorder.
AB  - An 87-year-old woman had both Lewy body dementia and normal pressure
      hydrocephalus simultaneously. One should not automatically exclude the
      possibility of normal pressure hydrocephalus simply because another
      neurodegenerative disorder is present, especially if the second disorder masks
      typical symptoms of normal pressure hydrocephalus. Better identification of dual
      diagnosis patients could lead to improvements in gait and incontinence following
      ventriculoperitoneal or lumboperitoneal shunting, even if the natural history of
      the other neurodegenerative disease remains unchanged.

PMID- 18728811
TI  - Monotherapy for partial epilepsy: focus on levetiracetam.
AB  - Levetiracetam (LEV), the S-enantiomer of alpha-ethyl-2-oxo-1-pyrollidine
      acetamide, is a recently licensed antiepileptic drug (AED) for adjunctive therapy
      of partial seizures. Its mechanism of action is uncertain but it exhibits a
      unique profile of anticonvulsant activity in models of chronic epilepsy. Five
      randomized, double-blind, placebo-controlled trials enrolling adult or pediatric
      patients with refractory partial epilepsy have demonstrated the efficacy of LEV
      as adjunctive therapy, with a responder rate (>/=50% reduction in seizure
      frequency) of 28%-45%. Long-term efficacy studies suggest retention rates of 60%
      after one year, with 13% of patients seizure-free for 6 months of the study and
      8% seizure-free for 1 year. More recent studies illustrated successful conversion
      to monotherapy in patients with refractory epilepsy, and its effectiveness as a
      single agent in partial epilepsy. LEV has also efficacy in generalized
      epilepsies. Adverse effects of LEV, including somnolence, lethargy, and
      dizziness, are generally mild and their occurrence rate seems to be not
      significantly different from that observed in placebo groups. LEV also has no
      clinically significant pharmacokinetic interactions with other AEDs, or with
      commonly prescribed medications. The combination of effective antiepileptic
      properties with a relatively mild adverse effect profile makes LEV an attractive
      therapy for partial seizures.

PMID- 18728812
TI  - Treatment of adults with attention-deficit/hyperactivity disorder.
AB  - This review focuses on the treatment of attention deficit hyperactivity disorder
      (ADHD) in adults. It briefly addresses prevalence, diagnostic and differential
      diagnostic issues specific to adults. Stimulant medication, non-stimulant
      medication, and psychosocial treatments are thoroughly reviewed. For each class
      of medication possible mechanism of action, efficacy and side effects are
      summarized. Special attention is given to the pharmacological treatment for
      patients with adult ADHD and various comorbidities. In summary, stimulant
      medications are most effective and combined medication and psychosocial treatment
      is the most beneficial treatment option for most adult patients with ADHD.

PMID- 18728815
TI  - Treatment of adult ADHD: is current knowledge useful to clinicians?
AB  - Psychostimulant drugs have for decades been considered the cornerstone of ADHD
      treatment. Non-stimulant drugs have also been reported successful. However, many
      controlled studies exclude patients with comorbidities typical for patients seen
      in clinical setting. Many patients are also considered non-responders to
      medication. Current knowledge might not be directly useful to clinicians. The
      present article reviews the literature on pharmacological and psychotherapeutic
      treatment in adult ADHD emphasizing comorbidity and other clinically important
      factors, as well as ADHD specific outcomes. Thirty-three relevant studies of
      pharmacotherapy and three studies of psychotherapy were included. Most subjects
      had little current comorbidity, but some studies included subjects with substance
      use disorder. Significant effect of treatment on ADHD symptoms was found in most
      studies using pharmacotherapy and all studies of psychotherapy. Both positive and
      negative effects on comorbid anxiety and depression measures were reported.
      Pharmacotherapy did not seem to have effect on substance use disorder. Few
      pharmacotherapy studies conducted any long-term follow-up; two studies that did,
      found that most subjects had discontinued medication. A clear-cut dose-respons
      relationship was not substanciated. In conclusion, clinicians have good support
      for both pharmacological and psychotherapeutic treatment of ADHD in adults, but
      should take additional measures to deal with comorbidities as well as treatment
      adherence.

PMID- 18728814
TI  - Depression in Parkinson's disease: health risks, etiology, and treatment options.
AB  - Depression is found in about 30%-40% of all patients with Parkinson's disease
      (PD), but only a small percentage (about 20%) receive treatment. As a
      consequence, many PD patients suffer with reduced health-related quality of life.
      To address quality of life in depressed PD patients, we reviewed the literature
      on the health correlates of depression in PD (eg, cognitive function), etiology
      of depression in PD, and treatment options (ie, antidepressants,
      electroconvulsive therapy, and psychotherapy). The current review is unique in
      its focus on psychosocial aspects, as well as neuropathological factors, of
      depression in PD. Overall, we conclude that neurochemical (eg, serotonin) and
      psychosocial factors (eg, coping style, self-esteem, and social support)
      contribute to the affective disturbances found in this neuropsychiatric
      population. Therefore, we recommend that a multidisciplinary (eg,
      pharmacotherapeutic, psychoeducational, and/or psychotherapeutic) approach to
      treatment be taken with depressed PD patients.

PMID- 18728816
TI  - Optimizing levodopa therapy for Parkinson's disease with
      levodopa/carbidopa/entacapone: implications from a clinical and patient
      perspective.
AB  - After 40 years of clinical experience, levodopa remains the gold standard
      treatment for Parkinson's disease (PD) despite the recent emergence of a host of
      new therapies. Some physicians are cautious when prescribing levodopa because of
      its association with motor complications. Evidence now suggests that levodopa
      associated complications are a result of deep troughs in delivery of levodopa to
      the brain caused by the short plasma half-life of conventional levodopa
      formulations (levodopa and a dopa decarboxylase inhibitor [DDCI]). Dosing
      strategies, such as dose increases and dose fractionation, may be effective in
      the short term. For the longer-term, levodopa/carbidopa/entacapone provides
      pharmacokinetically optimized levodopa therapy that significantly increases the
      plasma half-life and bioavailability of levodopa, providing more consistent
      plasma levodopa levels without deep troughs. Evidence from clinical trials in PD
      patients experiencing re-emergence of symptoms due to wearing-off has
      consistently shown that levodopa/DDCI and entacapone significantly increases ON
      time and affords greater functionality, as measured by the Unified Parkinson's
      Disease Rating Scale (UPDRS) with conventional levodopa. These trials have also
      shown that levodopa/DDCI and entacapone is generally well tolerated, with notable
      adverse events including worsening dyskinesia, nausea and diarrhea. Patients
      experiencing re-emergence of symptoms due to wearing-off may benefit from
      optimized levodopa therapy with levodopa/carbidopa/entacapone.

PMID- 18728817
TI  - The relationship between early life stress and microstructural integrity of the
      corpus callosum in a non-clinical population.
AB  - BACKGROUND: Previous studies have examined the impact of early life stress (ELS)
      on the gross morphometry of brain regions, including the corpus callosum.
      However, studies have not examined the relationship between ELS and the
      microstructural integrity of the brain. METHODS: In the present study we
      evaluated this relationship in healthy non-clinical participants using diffusion
      tensor imaging (DTI) and self-reported history of ELS. RESULTS: Regression
      analyses revealed significant reductions in fractional anisotropy (FA) within the
      genu of the corpus callosum among those exposed to the greatest number of early
      life stressors, suggesting reduced microstructural integrity associated with
      increased ELS. These effects were most pronounced in the genu of the corpus
      callosum compared to the body and splenium, and were evident for females rather
      than males despite no differences in total ELS exposure between the sexes. In
      addition, a further comparison of those participants who were exposed to no ELS
      vs. three or more ELS events revealed lower FA in the genu of the corpus callosum
      among the ELS-exposed group, with trends of FA reduction in the body and the
      whole corpus callosum. By contrast, there were no relationships between ELS and
      volumetric analysis of the CC regions. The two group did not differ significantly
      on measures of current depression, stress or anxiety. CONCLUSION: Our results
      reveal that greater exposure to ELS is associated with microstructural
      alterations in the white matter in the absence of significant volumetric changes.
      Importantly, our results indicate that exposure to ELS is associated with
      abnormalities on DTI despite the absence of clinically significant psychiatric
      symptoms. Future studies are needed to determine whether specific types of ELS
      are more likely to impact brain structure and function.

PMID- 18728818
TI  - Functional MRI evidence for language plasticity in adult epileptic patients:
      Preliminary results.
AB  - The present fMRI study explores the cerebral reorganisation of language in
      patients with temporal lobe epilepsy, according to the age of seizures onset
      (early or late) and the hippocampal sclerosis (associated or not). Seven right
      handed control volunteers and seven preoperative adult epileptic patients
      performed a rhyme decision (language condition) and a visual detection (control
      condition) tasks in visually presented words and unreadable characters,
      respectively. All patients were left hemisphere dominant for language.
      Appropriate statistical analyses provided the following preliminary results: (1)
      patients compared with healthy subjects showed lower degree of hemispheric
      lateralization with supplementary involvement of the right hemisphere; (2) the
      degree of hemispheric specialization depends on the considered region; (3)
      patients with early seizures show signs of temporal and parietal reorganization
      more frequently than patients with late onset of seizures; (4) patients with
      early seizures show a tendency for intra-hemispheric frontal reorganisation; (5)
      associated hippocampal sclerosis facilitates the inter-hemispheric shift of
      temporal activation. Although our patients were left hemisphere predominant for
      language, the statistical analyses indicated that the degree of lateralization
      was significantly lower than in healthy subjects. This result has been considered
      as the indication of atypical lateralization of language.

PMID- 18728819
TI  - Review of frovatriptan in the treatment of migraine.
AB  - Triptans are recommended for the acute treatment of moderate to severe migraine
      or failure to respond to other acute migraine treatments. Seven triptans are
      available providing a wide range of choices. These triptans are more similar than
      dissimilar but patients do note differences in effectiveness and in tolerance.
      Also migraine situations may differ from attack to attack, providing the
      opportunity to exploit the uniqueness of a particular triptan. Frovatriptan has a
      uniquely long-half life, five times that of other triptans. This provides the
      opportunity to use frovatriptan in mini-prophylaxis such as in menstrual-related
      migraine and other situations, as well as use in long-lasting or recurrent
      migraine.

PMID- 18728820
TI  - Pharmacological management of panic disorder.
AB  - Panic disorder (PD) is a disabling condition which appears in late adolescence or
      early adulthood and affects more frequently women than men. PD is frequently
      characterized by recurrences and sometimes by a chronic course and, therefore,
      most patients require long-term treatments to achieve remission, to prevent
      relapse and to reduce the risks associated with comorbidity. Pharmacotherapy is
      one of the most effective treatments of PD. In this paper, the pharmacological
      management of PD is reviewed. Many questions about this effective treatment need
      to be answered by the clinician and discussed with the patients to improve
      her/his collaboration to the treatment plan: which is the drug of choice; when
      does the drug become active; which is the effective dose; how to manage the side
      effects; how to manage nonresponse; and how long does the treatment last.
      Moreover, the clinical use of medication in women during pregnancy and
      breastfeeding or in children and adolescents was reviewed and its risk-benefit
      balance discussed.

PMID- 18728822
TI  - Resting and reactive frontal brain electrical activity (EEG) among a non-clinical
      sample of socially anxious adults: does concurrent depressive mood matter?
AB  - A number of studies have noted that the pattern of resting frontal brain
      electrical activity (EEG) is related to individual differences in affective style
      in healthy infants, children, and adults and some clinical populations when
      symptoms are reduced or in remission. We measured self-reported trait shyness and
      sociability, concurrent depressive mood, and frontal brain electrical activity
      (EEG) at rest and in anticipation of a speech task in a non-clinical sample of
      healthy young adults selected for high and low social anxiety. Although the
      patterns of resting and reactive frontal EEG asymmetry did not distinguish among
      individual differences in social anxiety, the pattern of resting frontal EEG
      asymmetry was related to trait shyness after controlling for concurrent
      depressive mood. Individuals who reported a higher degree of shyness were likely
      to exhibit greater relative right frontal EEG activity at rest. However, trait
      shyness was not related to frontal EEG asymmetry measured during the speech
      preparation task, even after controlling for concurrent depressive mood. These
      findings replicate and extend prior work on resting frontal EEG asymmetry and
      individual differences in affective style in adults. Findings also highlight the
      importance of considering concurrent emotional states of participants when
      examining psychophysiological correlates of personality.

PMID- 18728821
TI  - Adenylyl cyclase-cyclicAMP signaling in mood disorders: role of the crucial
      phosphorylating enzyme protein kinase A.
AB  - Mood disorders are among the most prevalent and recurrent forms of psychiatric
      illnesses. In the last decade, there has been increased understanding of the
      biological basis of mood disorders. In fact, novel mechanistic concepts of the
      neurobiology of unipolar and bipolar disorders are evolving based on recent pre
      clinical and clinical studies, most of which now focus on the role of signal
      transduction mechanisms in these psychiatric illnesses. Particular investigative
      emphasis has been given to the role of phosphorylating enzymes, which are crucial
      in regulating gene expression and neuronal and synaptic plasticity. Among the
      most important phosphorylating enzyme is protein kinase A (PKA), a component of
      adenylyl cyclase-cyclic adenosine monophosphate (AC-cAMP) signaling system. In
      this review, we critically and comprehensively discuss the role of various
      components of AC-cAMP signaling in mood disorders, with a special focus on PKA,
      because of the interesting observation that have been made about its involvement
      in unipolar and bipolar disorders. We also discuss the functional significance of
      the findings regarding PKA by discussing the role of important PKA substrates,
      namely, Rap-1, cyclicAMP-response element binding protein, and brain-derived
      neurotrophic factor. These studies suggest the interesting possibility that PKA
      and related signaling molecules may serve as important neurobiological factors in
      mood disorders and may be relevant in target-specific therapeutic interventions
      for these disorders.

PMID- 18728823
TI  - Rasagiline in treatment of Parkinson's disease.
AB  - Rasagiline (N-propargyl-1 (R)-aminoindan) is a novel propargylamine,
      irreversible, selective monoamine oxidase inhibitor for treatment of Parkinson's
      disease (PD), a progressive condition associated with degeneration of
      dopaminergic neurons in the substantia nigra. Rasagiline inhibits striatal
      dopamine metabolism, thereby providing relief from motor symptoms of PD. It may
      be dosed once daily and, unlike selegiline, it is metabolized to non-amphetamine
      compounds. In a large clinical trial, rasagiline has proved effective, safe, and
      well tolerated in early PD as monotherapy. In two phase III clinical trials in
      advanced PD with motor fluctuations, rasagiline as an adjunct to levodopa
      significantly decreases "off" time. In animal models of PD, data supports a
      neuroprotective effect of rasagiline, and its active metabolite aminoindan.
      Analysis of delayed-start clinical trial suggests the potential for disease
      modification, and further trials are examining this effect.

PMID- 18728824
TI  - Prevalence of eating disorders and eating attacks in narcolepsy.
AB  - Narcoleptic patients suffer frequently from obesity and type II diabetes. Most
      patients show a deficit in the energy balance regulating orexinergic system.
      Nevertheless, it is not known, why narcoleptic patients tend to be obese. We
      examined 116 narcoleptic patients and 80 controls with the structured interview
      for anorectic and bulimic eating disorders (SIAB) to test the hypothesis that
      typical or atypical eating attacks or eating disorders may be more frequent in
      narcoleptic patients. No difference in the current prevalence of eating disorders
      bulimia nervosa, binge eating disorder, or anorexia nervosa was found, nor was
      the frequency of eating attacks higher in the narcolepsy group. We conclude that
      present eating disorders and eating attacks as defined in DSM IV are not the
      reason for the observed differences in body composition. Additional factors, such
      as basal metabolic rates and lifestyle factors need to be considered.

PMID- 18728825
TI  - Effects of milnacipran on binge eating - a pilot study.
AB  - Selective serotonin reuptake inhibitors and selective norepinephrine reuptake
      inhibitors are effective in the treatment of bulimia nervosa. There have been
      relatively few studies of the efficacy of specific serotonin and norepinephrine
      reuptake inhibitors in the treatment of eating disorders. Twenty-five outpatients
      with binge eating episodes, diagnosed as anorexia nervosa, binge-eating/purging
      type, bulimia nervosa/purging type, or bulimia nervosa/non-purging type, were
      treated with milnacipran and 20 patients completed the 8-week study. Symptom
      severity was evaluated using the Bulimic Investigatory Test, Edinburgh (BITE)
      self-rating scale before administration of milnacipran and after 1, 4, and 8
      weeks treatment. The scores improved after 8 weeks, especially drive to, and
      regret for, binge eating. Milnacipran was more effective in patients without
      purging and in younger patients, while there was no difference in the efficacy of
      milnacipran among subtypes of eating disorders.

PMID- 18728827
TI  - [Not Available].

PMID- 18728826
TI  - A review of nabilone in the treatment of chemotherapy-induced nausea and
      vomiting.
AB  - Chemotherapy-induced nausea and vomiting (CINV) in cancer patients places a
      significant burden on patients' function and quality of life, their families and
      caregivers, and healthcare providers. Despite the advances in preventing CINV, a
      substantial proportion of patients experience persistent nausea and vomiting.
      Nabilone, a cannabinoid, recently received Food and Drug Administration approval
      for the treatment of the nausea and vomiting in patients receiving cancer
      chemotherapy who fail to achieve adequate relief from conventional treatments.
      The cannabinoids exert antiemetic effects via agonism of cannabinoid receptors
      (CB1 and CB2). Clinical trials have demonstrated the benefits of nabilone in
      cancer chemotherapy patients. Use of the agent is optimized with judicious dosing
      and selection of patients.

PMID- 18728828
TI  - Cost-effectiveness analysis of electrochemotherapy with the Cliniporatortrade
      mark vs other methods for the control and treatment of cutaneous and subcutaneous
      tumors.
AB  - INTRODUCTION: Tumors of any histological origin can give rise to cutaneous and
      subcutaneous metastases during follow-up. This study aims to evaluate the costs
      and benefits of electrochemotherapy (ECT) with the Cliniporatortrade mark vs
      other currently used methods in the control and treatment of cutaneous and
      subcutaneous advanced neoplasms. MATERIALS AND METHODS: A cost-effectiveness
      analysis was carried out on ECT using the Cliniporator vs other techniques
      (radiotherapy, hyperthermia associated with radiotherapy and chemotherapy,
      interferon-alpha, and isolated limb perfusion) for the control and treatment of
      cutaneous and subcutaneous neoplasms. The direct health costs were attributed a
      value according to the Italian National Healthcare System. Resource consumption
      and clinical outcomes were derived from cost survey data collection and
      literature review. RESULTS: ECT is cost-effective with an incremental cost
      effectiveness ratio (ICER) of euro1,571.53 to achieve a further additional
      response. Radiotherapy and interferon-alpha are the least effective strategies. A
      combination of hyperthermia, chemotherapy, radiotherapy, and interferon-alpha
      treatment are dominated by ECT (more costly and less effective). Isolated limb
      perfusion is the most effective treatment, but is very costly (euro18,530.47)
      because of the use of antiblastic drugs (TNFalpha), with an ICER of
      euro92,717.29. CONCLUSIONS: After sensitivity analysis, the study results confirm
      the favorable cost-effectiveness ratio of ECT with the Cliniporator and justify
      its wider use.

PMID- 18728829
TI  - Nonlinear analysis of the heartbeats in public patient ECGs using an automated
      PD2i algorithm for risk stratification of arrhythmic death.
AB  - Heart rate variability (HRV) reflects both cardiac autonomic function and risk of
      arrhythmic death (AD). Reduced indices of HRV based on linear stochastic models
      are independent risk factors for AD in post-myocardial infarct cohorts. Indices
      based on nonlinear deterministic models have a significantly higher sensitivity
      and specificity for predicting AD in retrospective data. A need exists for
      nonlinear analytic software easily used by a medical technician. In the current
      study, an automated nonlinear algorithm, the time-dependent point correlation
      dimension (PD2i), was evaluated. The electrocardiogram (ECG) data were provided
      through an National Institutes of Health-sponsored internet archive (PhysioBank)
      and consisted of all 22 malignant arrhythmia ECG files (VF/VT) and 22 randomly
      selected arrhythmia files as the controls. The results were blindly calculated by
      automated software (Vicor 2.0, Vicor Technologies, Inc., Boca Raton, FL) and
      showed all analyzable VF/VT files had PD2i < 1.4 and all analyzable controls had
      PD2i > 1.4. Five VF/VT and six controls were excluded because surrogate testing
      showed the RR-intervals to contain noise, possibly resulting from the low
      digitization rate of the ECGs. The sensitivity was 100%, specificity 85%,
      relative risk > 100; p < 0.01, power > 90%. Thus, automated heartbeat analysis by
      the time-dependent nonlinear PD2i-algorithm can accurately stratify risk of AD in
      public data made available for competitive testing of algorithms.

PMID- 18728830
TI  - New approaches in the treatment of HIV/AIDS - focus on maraviroc and other CCR5
      antagonists.
AB  - Treatment of HIV-1 infection has produced dramatic success for many patients.
      Nevertheless, viral resistance continues to limit the efficacy of currently
      available agents in many patients. The CCR5 antagonists are a new class of
      antiretroviral agents that target a necessary coreceptor for viral entry of many
      strains of HIV-1. Recently, the first agent within this class, maraviroc, was
      approved by a number of regulatory agencies, including the Food and Drug
      Administration. Herein we review the role of the CCR5 receptor in HIV-1 infection
      and potential methods to target it in anti-HIV-1 therapy. We review the various
      categories of agents and discuss specific agents that have progressed to clinical
      study. We discuss in detail the recently approved, first in class CCR5
      antagonist, maraviroc, and discuss aspects of resistance to CCR5 antagonism and
      the potential role of CCR5 antagonism in the management of HIV-1 infection.

PMID- 18728831
TI  - Towards a new standard of perioperative fluid management.
AB  - Recent studies suggest that current fluid strategies may result in excessive
      administration of both fluids and electrolytes. Perioperative fluid
      administration is dictated by an algorithmic approach, taking account of pre
      operative deficit, maintenance requirements, and extrapolated third space losses.
      Salt and water overload is associated with pulmonary edema, ileus, and delayed
      wound healing. Within an intensive care population, there is a strong correlation
      between excessive intravascular volume and subsequent mortality, morbidity, and
      length of stay. Increasing weight has been shown to correspond with mortality,
      while achieving a negative balance within the first 72 hours of ITU admission has
      been postulated as an independent predictor of survival. Should a "restricted"
      rather than a "liberal" perioperative fluid regimen be employed? It is arguable
      that prevailing fluid therapy is not evidence-based. Recent observations suggest
      that restraint in fluid administration correlates with better outcome. The
      development of a protocol-based fluid optimization program may help minimize the
      risk of perioperative fluid overload.

PMID- 18728832
TI  - Use of ethinylestradiol/drospirenone combination in patients with the polycystic
      ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is one of the most common endocrine/metabolic
      disorders found in women, affecting approximately 105 million women worldwide. It
      is characterized by ovulatory dysfunction, often presenting as oligomenorrhea or
      amenorrhea and either clinical or biochemical hyperandrogenism. Combined oral
      contraceptive (COC) therapy has long been a cornerstone of care for women with
      PCOS. COC therapy often provides clinical improvement in the areas of excessive
      hair growth, unpredictable menses, acne, and weight gain. One of the main issues
      in COC therapy is choosing the most appropriate progestin component to provide
      the greatest anti androgenic effects. Drospirenone, a relatively new progestin,
      has shown benefit in the PCOS population when used in conjunction with ethinyl
      estradiol. We now review the role of COCs in PCOS, focusing specifically on
      drospirenone. Controversy over metabolic effects of COCs in PCOS is also
      discussed.

PMID- 18728839
TI  - Raltegravir: first in class HIV integrase inhibitor.
AB  - On October 16, 2007, the US Food and Drug Administration (FDA) approved
      raltegravir for treatment of human immunodeficiency virus (HIV)-1 infection in
      combination with other antiretroviral agents in treatment-experienced adult
      patients who have evidence of viral replication and HIV-1 strains resistant to
      multiple antiretroviral agents. Raltegravir is first in a novel class of
      antiretroviral drugs known as integrase inhibitors. It has demonstrated potent
      anti HIV activity in both antiretroviral treatment-naive and experienced
      patients. The most common adverse events reported with raltegravir during phase 2
      and 3 clinical trials were diarrhea, nausea, and headache. Laboratory
      abnormalities include mild elevations in liver transaminases and creatine
      phosphokinase.

PMID- 18728833
TI  - Fluticasone furoate nasal spray in the treatment of allergic rhinitis.
AB  - Allergic rhinitis (AR) is a prevalent disease with great morbidity and
      significant societal and economic burden. Intranasal corticosteroids are
      recommended as first-line therapy for patients with moderate-to-severe disease,
      especially when nasal congestion is a major component of symptoms. To compare the
      efficacy and safety profile of different available intranasal corticosteroids for
      the treatment of AR, it is important to understand their different structures and
      pharmacokinetic and pharmacodynamic properties. Knowledge of these drugs has
      increased tremendously over the last decade. Studies have elucidated mechanisms
      of action, pharmacologic properties, and the clinical impact of these drugs in
      allergic respiratory diseases. Although the existing intranasal corticosteroids
      are already highly efficient, the introduction of further improved formulations
      with a better efficacy/safety profile is always desired. Fluticasone furoate
      nasal spray is a new topical corticosteroid, with enhanced-affinity and a unique
      side-actuated delivery device. As it has high topical potency and low potential
      for systemic effects, it is a good candidate for rhinitis treatment.

PMID- 18728838
TI  - Review of miglustat for clinical management in Gaucher disease type 1.
AB  - Gaucher disease is a progressive lysosomal storage disorder caused by the
      deficiency of glucocerebrosidase, and characterized by intralysosomal storage of
      glucosylceramide that leads to dysfunction in multiple organ systems. Intravenous
      enzyme replacement with imiglucerase is the accepted standard for treatment of
      symptomatic patients and has been effective in reducing many of the signs and
      symptoms of type I Gaucher disease in the majority of patients without serious
      adverse effects. An alternative therapeutic approach is substrate reduction
      therapy with N-butyldeoxynojirimycin (NB-DNJ) (miglustat; Zavesca((R))), an imino
      sugar that reversibly inhibits glucosylceremide synthase and reduces
      intracellular storage of glucosylceramide. Miglustat was recently approved in
      Europe and the United States for symptomatic patients with mild to moderate
      clinical manifestations for whom enzyme replacement therapy is not an option.
      This review article discusses the results of clinical studies and use of
      miglustat as a therapeutic agent in patients with type I Gaucher disease.

PMID- 18728835
TI  - Zosyn (piperacillin/tazobactam) reformulation: Expanded compatibility and
      coadministration with lactated Ringer's solutions and selected aminoglycosides.
AB  - Zosyn((R)) , also known as Tazocin((R)) for injection, contains piperacillin and
      tazobactam and was approved by the US Food and Drug Administration in 1993 for
      the treatment of indicated serious infections. In 1995, United States
      Pharmacopoeia and European Pharmacopoeias reduced the particulate limit for
      injectables by 40%, based on general safety concerns. Wyeth attempted to control
      sporadic batch failures (associated with increased particulate formation) by
      shortening product expiration dating from 36 to 24 months and optimizing the
      stopper siliconization process. These modifications did not correct the problem
      completely. Wyeth reformulated Zosyn by incorporating two stabilizing functional
      excipients, ethylene diamine tetraacetic acid disodium salt (EDTA disodium) and
      sodium citrate, which solved the particulate formation problem. These two
      functional excipients also allowed for the first time Y-site coadministration of
      reformulated Zosyn product with amikacin and gentamicin at specific doses and
      concentrations, and with certain diluents, and the use of Ca(++) ion-containing
      Lactated Ringer's for admixture preparation. Reformulated Zosyn (approved 2005)
      may provide useful options of drug administration to healthcare professionals to
      lessen levels of particulates. Supportive data is provided for the expanded
      compatibility of reformulated Zosyn with different types of Ringer's solutions
      used globally and for the Y-site coadministration of amikacin and gentamicin
      aminoglycosides.

PMID- 18728836
TI  - Conivaptan: a step forward in the treatment of hyponatremia?
AB  - Hyponatremia is one of the most common electrolyte abnormalities linked to
      adverse outcomes and increased mortality in hospitalized patients. While the
      differential diagnosis for hyponatremia is diverse, most cases stem from arginine
      vasopressin (AVP) dysregulation, where hypoosmolality fails to suppress AVP
      synthesis and release. The physiological effects of AVP are currently known to
      depend on its interaction with any of 3 receptor subtypes V1A, V2, and V1B.
      Activation of V2 by AVP is the key in renal water regulation and maintenance of
      total body volume and plasma tonicity. Despite the long-recognized problem with
      excess AVP in euvolemic and hypervolemic hyponatremia, traditional therapeutic
      options have relied on nonspecific and potentially problematic strategies. More
      recently, a new class of drugs, introduced as "aquaretics," has gained great
      attention among clinicians because of its ability to correct hyponatremia via
      direct competitive inhibition of AVP at V2 receptors to induce renal electrolyte
      free water excretion. In this paper, we aim to review available clinical data on
      the only FDA-approved aquaretic, dual V1A/V2 receptor antagonist conivaptan,
      discuss its clinical indications, efficacy, safety profile, and comment on its
      clinical limitations.

PMID- 18728844
TI  - Alemtuzumab in the up-front setting.
AB  - Alemtuzumab is a humanized chimeric monoclonal antibody targeting CD52. Although
      this agent already has an important role in the treatment of chronic lymphocytic
      leukemia (CLL), many of its uses are still being defined. Early trials showed
      alemtuzumab's value in refractory disease and helped to define its excellent
      activity in the bone marrow, spleen and 17p deleted patients. The CAM307 trial
      has demonstrated alemtuzumab's efficacy as monotherapy in the front-line setting,
      and ultimately led to its FDA approval as frontline therapy. Especially promising
      is the trend toward improved response in patients with high risk cytogenic
      abnormalities (17p del, 11q del, trisomy 12). The various consolidation trials
      have also provided promising results of achieving eradication of minimal residual
      disease (MRD). Although the ultimate benefit of achieving MRD negativity remains
      under investigation, alemtuzumab's potent activity on the bone marrow will likely
      make it an important part of combination therapy.

PMID- 18728840
TI  - Review of the combined contraceptive vaginal ring, NuvaRing.
AB  - The purpose of this review was to test contraceptive efficacy, cycle control,
      tolerability, and acceptability as found in the non-comparative studies with
      NuvaRing((R)) by those found in the randomized trials comparing NuvaRing and
      combined oral contraceptives (COCs). All large non-comparative studies and all
      relevant randomized controlled trials (RCTs) between NuvaRing and a COC up to and
      including December 2006 were analyzed. Two large multi-center registration
      studies, 1 large daily clinical practice study, and 6 RCTs comparing NuvaRing and
      a COC were identified. The findings in the non-comparative studies were confirmed
      in the RCTs. Contraceptive efficacy was high showing no significant differences
      in comparison with the COC; cycle control was good and consistently better than
      that of the COC; compliance was high and comparable with that of the pill; the
      incidence of adverse events such as breast tenderness, headache, and nausea was
      low, but not lower than with the COC despite a halving of the systemic exposure
      to ethinyl estradiol (EE) with NuvaRing compared with a 30-mug EE-containing COC;
      the incidence of local and ring-related events was low but higher than with the
      COC, leading to higher discontinuation rates among NuvaRing users; acceptability
      was high and comparable between both contraceptives, resulting in a global
      improvement of sexual function with both methods. After study completion, women
      using NuvaRing were more likely to continue with their method than women using a
      COC. The good results with respect to contraceptive efficacy, cycle control,
      tolerability, and acceptability as achieved with NuvaRing in the large non
      comparative registration studies were confirmed in the RCTs comparing NuvaRing
      with different COCs.

PMID- 18728837
TI  - Prevention of chemotherapy-induced nausea and vomiting: focus on fosaprepitant.
AB  - Fosaprepitant is a prodrug of aprepitant, a neurokinin(1) (NK(1)) receptor
      antagonist used in prophylactic antiemetic regimens used prior to cytotoxic
      chemotherapy. Fosaprepitant is being developed to provide a parenterally
      administered alternative to the orally administered aprepitant. Fosaprepitant is
      rapidly converted to aprepitant and an intravenous dose of 115 mg is
      bioequivalent to 125 mg orally, with similar plasma concentrations at 24 hours.
      In phase I and II trials fosaprepitant shows efficacy, but the large randomized
      efficacy studies have utilized aprepitant. When it is added to dexamethasone and
      a 5HT(3) receptor antagonist on day 1 prior to chemotherapy aprepitant improves
      the control of acute post chemotherapy emesis and when continued on days 2 and 3
      with dexamethasone it demonstrated even greater improvement in the control of
      delayed emesis. This has been shown with both cisplatin-containing regimens and
      those based upon cyclophosphamide and an anthracycline. Fosaprepitant is well
      tolerated with mild to moderate venous irritation being the only additional
      toxicity to those seen with oral aprepitant, and that is a function of dose,
      concentration, and infusion rate. Headaches are the other toxicity most commonly
      reported. Fosaprepitant can be used as a parenteral alternative to aprepitant in
      regimens to control chemotherapy-induced emesis.

PMID- 18728842
TI  - "One pill, once daily": what clinicians need to know about Atriplatrade mark.
AB  - As the number of persons chronically prescribed antiretrovirals has grown and the
      realization that antiretrovirals are required to be continued for life,
      pharmaceutical manufacturers have developed new classes of agents, improved the
      pharmacokinetics of marketed products through dosing reformulations, and in an
      effort to maximize success with respect to adherence, compiled into a single
      dosing unit all necessary elements for an antiretroviral regimen. Atriplatrade
      mark represents the first ever fixed-dose combination antiretroviral available.
      This article reviews currently available data on this agent, the impact of
      resistance on clinical use and implementation, as well as extensive descriptions
      of the pharmacokinetics, adverse effects and drug-interactions warranting
      consideration. Whether beginning in a naive patient or switching from other
      regimens for tolerability issues, Atriplatrade mark represents a viable option.
      Its demonstrated advantages with respect to lipid and hematologic parameters and
      equivalent incidence of renal toxicity are tempered by the findings of bone
      mineral density decreases, however. Combining multiple mechanisms of action in a
      single dosing unit appears to improve efficacy, increase the likelihood for
      adherence and maintain viral suppression compared to administering these agents
      independently. It is suggested other pharmaceutical companies assess the
      potential to replicate this for the remaining antiretrovirals.

PMID- 18728843
TI  - A review of nasal polyposis.
AB  - Nasal polyps are common, affecting up to four percent of the population. Their
      etiology remains unclear, but they are known to have associations with allergy,
      asthma, infection, cystic fibrosis, and aspirin sensitivity. They present with
      nasal obstruction, anosmia, rhinorrhoea, post nasal drip, and less commonly
      facial pain. Clinical examination reveals single or multiple grey polypoid masses
      in the nasal cavity. Computerized tomography allows evaluation of the extent of
      the disease and is essential if surgical treatment is to be considered.
      Management of polyposis involves a combination of medical therapy and surgery.
      There is good evidence for the use of corticosteroids (systemic and topical) both
      as primary treatment and as postoperative prophylaxis against recurrence.
      Surgical treatment has been refined significantly over the past twenty years with
      the advent of endoscopic sinus surgery and, in general, is reserved for cases
      refractory to medical treatment. Recurrence of the polyposis is common with
      severe disease recurring in up to ten percent of patients.

PMID- 18728841
TI  - Use of ibandronate in the prevention of skeletal events in metastatic breast
      cancer.
AB  - Bone metastasis from breast cancer often cause significant morbidity including
      pain, impaired mobility, pathological fracture, and spinal cord compression.
      Bisphosphonates play an important role in preventing these skeletal related
      events and are the standard of care for patients with bone metastasis from breast
      cancer. Ibandronate is a highly potent bisphosphonate available in both
      intravenous and oral preparations. It has been shown in clinical trials to be
      effective in reducing skeletal complications and also significantly improve
      quality of life up to 96 weeks. Unlike other intravenous bisphosphonates,
      ibandronate has minimal renal toxicity, allowing safe outpatient administration,
      reducing the need for hospital attendance and safety monitoring. Early trials
      have shown ibandronate may also be effective in high doses for palliation of
      opioid-resistant pain from bone metastasis, and as a second-line agent in
      patients developing a skeletal complication whilst receiving another
      bisphosphonate.

PMID- 18728846
TI  - Enfuvirtide antiretroviral therapy in HIV-1 infection.
AB  - It has been over 25 years since the first diagnosis of what would be known as
      AIDS. Although great strides in anti-HIV therapeutics have been made, there is
      still a great need for antiretrovirals that are effective against drug-resistant
      HIV. Enfuvirtide (ENF) is the first of a new class of fusion inhibitors to be
      approved by the US Food and Drug Administration for use in combination with other
      antiretroviral agents among HIV-1 infected patients with previous treatment
      experience. The inclusion of enfuvirtide in an optimized antiretroviral
      background regimen for the treatment of HIV-1 infected (treatment-experienced)
      patients followed the success of two critical clinical trials (TORO: T20 vs
      Optimized Regimen Only I and II). Even though injection-site reactions persisted
      in these trials, improved virological and immunological responses were observed
      among patients. Challenges associated with ENF treatment include the high cost of
      the drug, injection-site reactions, determining the optimal time to initiate
      treatment, and the potential for the selection of drug resistant mutants and
      viral evolution. ENF is a promising novel treatment for HIV infected individuals
      whose choices for effective treatment are limited by previous treatment and
      resistance. Understanding the implications of viral fitness and evolution in the
      presence of ENF treatment is crucial in determining effective and safe treatment
      regimens, particularly among treatment-experienced patients.

PMID- 18728848
TI  - Managing anemia in lymphoma and multiple myeloma.
AB  - Anemia is common in cancer, and lymphoproliferative disease is no exception.
      Erythropoiesis-stimulating agents (ESA) have been used for renal anemia since
      1986, and considerably later in cancer anemia. The first studies were published
      around 1993, but the use of ESA did not become common in cancer anemia until in
      the late 1990s. Cancer anemia is still under-treated. This review gives an
      overview of the use of ESA in hematologic malignancies. A background is given
      about this treatment in the cancer field generally. The pathophysiology of cancer
      anemia is described with special emphasis on the disturbances in iron metabolism.
      Functional iron deficiency has been shown to be both frequent and important as a
      hindrance for response to ESA treatment, and recent studies are reported in some
      detail, where the use of intravenous iron was shown to improve the response rate
      of ESA treatment.

PMID- 18728853
TI  - Docetaxel for the post-surgery treatment of patients with node-positive breast
      cancer.
AB  - Adjuvant chemotherapy reduces risk of relapse and cancer-related mortality in
      early stage breast cancer. Over the last decade, taxanes (paclitaxel and
      docetaxel) have been incorporated into various adjuvant trials and have
      demonstrated a significant benefit in the management of early stage breast
      cancer. Clinical trials using combinations of taxanes with targeted therapy have
      also shown considerable activity in breast cancer. This article reviews the
      pharmacology of docetaxel, a semi-synthetic taxane, and the clinical trials
      supporting its use in patients with node-positive breast cancer.

PMID- 18728856
TI  - Thin film rupture and polymer flow.
AB  - An account is given of the current state of understanding the rupture of
      ultrathin polymer films (<100 nm), mostly based on polystyrene (PS) on Si or SiO
      substrates. These systems have proved to be an ideal testing ground for the
      concepts of hydrodynamics of confined systems in which intermolecular
      interactions play a driving role. The focus of the article is on the highly
      successful comparison of experimental investigations with theoretical
      descriptions of these model systems.

PMID- 18728852
TI  - Single-day treatment for orolabial and genital herpes: a brief review of
      pathogenesis and pharmacology.
AB  - Herpes simplex virus (HSV) infection is a highly prevalent condition responsible
      for significant morbidity and occasional mortality each year. Approximately half
      of all patients infected by HSV will experience at least one recurrence in their
      lifetime. For these recurrences, traditional therapy has included both
      suppressive and episodic treatment with nucleoside analogs. In regards to
      episodic treatment, 2- to 5-day oral regimens are best studied and most commonly
      reported. As with any medical condition having a well-understood mechanism of
      action and targeted treatment, therapeutic intervention is only as effective as
      allowed by patient compliance. Based on these concerns, recent studies have
      focused on shorter, less complicated, and more affordable options. This review
      delineates the evidence for single-day treatments of orolabial and genital
      herpes. Randomized, double-blind studies of both valacyclovir and famciclovir as
      single-day episodic therapy for HSV have been reported in the literature.
      Although no head-to-head studies between the drugs have been performed, both
      regimens produced significant improvement in healing time and symptom resolution
      over placebo. Single-day therapy for HSV infection is appealing for multiple
      reasons. First, it simplifies the regimen, increasing likelihood of patient
      compliance. Additionally, it allows complete delivery of the medication at the
      onset of symptoms, when viral replication is highest and intervention has
      greatest effect. Lastly, the reduced number of pills necessary for single versus
      multiple day therapy decreases the overall cost of treatment per episode, an
      important factor in modern-day healthcare.

PMID- 18728850
TI  - Treating psoriasis with adalimumab.
AB  - Psoriasis is a common, chronic, inflammatory skin disease that can have a
      significant impact on the quality of life of those who are afflicted. Recent
      advances in the understanding of the pathophysiology of psoriasis have led to the
      development of new, genetically engineered, targeted therapies for this disease.
      Among the most successful strategies for treatment has been the use of biologic
      immunotherapies targeting tumor necrosis factor alpha (TNF). Recent research has
      evaluated the efficacy and safety of a new anti-TNF agent, adalimumab. Adalimumab
      is a human monoclonal antibody that is approved by the US Food and Drug
      Administration (FDA) and the European Medicines Agency (EMEA) for the treatment
      of rheumatoid arthritis and psoriatic arthritis. Recently released data from
      large, randomized clinical trials suggests that adalimumab has significant
      efficacy for the treatment of chronic plaque psoriasis and is well tolerated.
      Thus, adalimumab seems to be a promising therapeutic approach for patients who
      suffer from moderate to severe plaque psoriasis.

PMID- 18728857
TI  - Dimer-induced stabilization of H adsorbate cluster on BN(0001) surface.
AB  - Using first-principles calculations, we have studied successive adsorption of
      hydrogen atoms on a sp2-bonded boron nitride graphitic sheet. Our calculations
      show that clustering proceeds through the creation of contiguous H-H orthodimer
      structures stabilizing the H adsorbate cluster on the BN(0001) surface, leading
      eventually to the formation of hydrogen-contiguous boat-shaped quartets.

PMID- 18728845
TI  - Developments in the management of autosomal dominant polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent life-
      threatening, hereditary disease. ADPKD is more common than sickle cell anemia,
      cystic fibrosis, muscular dystrophy, hemophilia, Down's syndrome, and
      Huntington's disease combined. ADPKD is a multisystemic disorder characterized by
      the progressive development of renal cysts and marked renal enlargement.
      Structural and functional renal deterioration occurs in ADPKD patients and is the
      fourth leading cause of end-stage renal disease (ESRD) in adults. Aside from the
      renal manifestations, extrarenal structural abnormalities, such as liver cysts,
      cardiovascular abnormalities, and intracranial aneurysms may lead to morbidity
      and mortality. Recent studies have identified prognostic factors for progressive
      renal impairment including gender, race, age, proteinuria, hematuria,
      hypertension and increased left ventricular mass index (LVMI). Early diagnosis
      and better understanding of the pathophysiology of the disease provides the
      opportunity to aggressivly treat hypertension with renin-angiotensin-aldosterone
      system inhibitors and thereby potentially reduce LVMI, prevent cardiovascular
      morbidity and mortality and slow progression of the renal disease.

PMID- 18728858
TI  - Dipolar molecular rotors in the metal-organic framework crystal IRMOF-2.
AB  - Rotating polar linker groups in the cubic metal-organic framework single crystal
      known as IRMOF-2 were investigated for freedom of motion, response to an external
      electric field, and effects of dipole-dipole interactions. The crystals consist
      of octahedrally coordinated zinc oxide clusters linked by the bromoterephthalate
      group, which contains a rotatable bromo-p-phenylene moiety. We confirmed the
      rotation by dielectric spectroscopy and found a 7.3 kcal mol(-1) barrier. The non
      polar analog, IRMOF-1, containing terephthalic acid, was used as a control
      system. DFT and MP2 computations of the rotational barrier yield results in
      agreement with the observation, with B3LYP/SDD being the best. A Monte Carlo
      analysis of the equilibrium polarization fluctuations was used to assess the
      possibility of polar ordering and the potential for electro-optic applications.

PMID- 18728851
TI  - Treating refractory leukemias in childhood, role of clofarabine.
AB  - Approximately 4000 children and adolescents under the age of 20 years develop
      acute leukemia per year in the US. Acute lymphoblastic leukemia (ALL) is the most
      common pediatric cancer. Despite impressive improvements in outcome, relapsed ALL
      is the fourth most common pediatric malignancy. Therapy for relapsed ALL remains
      unsatisfactory, and the majority of relapse patients still succumb to leukemia.
      Between one-third and one-half of patients with acute myelogenous leukemia (AML)
      relapse, and no standard therapy is recognized for patients with relapsed and/or
      refractory AML. Novel therapeutic agents are needed to improve the cure rate for
      relapsed ALL and AML. Clofarabine is a next-generation nucleoside analog,
      designed to incorporate the best features and improve the therapeutic index of
      cladribine and fludarabine. Clofarabine inhibits both DNA polymerase and
      ribonucleotide reductase, leading to impaired DNA synthesis and repair, and
      directly induces apoptosis. Phase I and II single-agent trials in children have
      shown that clofarabine is safe and active in both myeloid and lymphoid
      relapsed/refractory acute leukemias. Clofarabine has been approved by the FDA for
      pediatric patients with relapsed/refractory ALL after at least 2 prior
      therapeutic attempts. Rational combinations of clofarabine with other active
      agents in refractory leukemias are currently under investigation.

PMID- 18728847
TI  - Leuprorelin depot injection: patient considerations in the management of
      prostatic cancer.
AB  - Hormone therapy is well established for treating patients with prostate cancer
      and remains the mainstay of the treatment of metastatic and locally advanced
      disease, this article reviews the rationale for its use, its different forms, and
      complications and controversies still surrounding some of its modalities.
      Availability of long-acting synthetic luteinizing hormone-releasing hormone
      (LHRH) agonists revolutionized the hormonal treatment of prostate cancer, and
      helped to avoid the emotional and psychological effects related to surgical
      castration. The depot formula has gained wide acceptance from both patients and
      physicians. This review emphasizes the newer, long-acting formula, leuprorelin
      (leuprolide acetate), especially the 6-month formula, its advantage over over
      shorter-acting depot products, and its potential to become a standard of care for
      patients eligible for androgen deprivation therapy.

PMID- 18728859
TI  - Multiscale effects in crystal grain growth and physical properties of metals.
AB  - A multiscale approach for the simulation of physical properties of metals is
      suggested and discussed. Grain growth in metals involves interactions at three
      distinct scale levels: the atomic scale (length of crystal lattice spacing),
      microscale (grain length) and macroscale. A simulation scheme should include
      these three levels. The crystalline microstructure is simulated by the Monte
      Carlo method. The average grain radius is then used to determine the yield
      strength from the Hall-Petch relationship for large grains and the inverse Hall
      Petch relationship for submicron-sized grains. The yield strength is then
      supplied to a continuum macroscale model. The normal grain growth, which has a
      theoretical solution for grain size as a function of time, is discussed in detail
      as a case study and conclusions are drawn with regard to more complex situations
      such as dynamic recrystallization.

PMID- 18728860
TI  - On the photodissociation of propadienylidene, l-C3H2.
AB  - We investigate the photochemistry and photodissociation dynamics of the linear
      C3H2 isomer propadienylidene by two-colour photofragment Doppler spectroscopy at
      excitation wavelengths between 260 and 230 nm, corresponding to excitation into
      the C1 A1 state. Propadienylidene is generated by pyrolysis from IC3H2Br. Almost
      complete conversion of the precursor can only be achieved at high pyrolysis
      temperatures. Two reaction channels, H-atom loss and loss of H2 molecules, are
      energetically close. Our results show that H-atom loss is indeed important in the
      investigated energy range. The Doppler profiles indicate that 34-37% of the
      excess energy is released as translation. The rates for H-atom loss are faster
      than the time resolution of our nanosecond-laser setup, kH > 10(8) s(-1).

PMID- 18728834
TI  - New approaches to managing asthma: a US perspective.
AB  - Despite remarkable advances in diagnosis and long-term management, asthma remains
      a serious public health concern. Newly updated expert guidelines emphasize the
      intra- and inter-individual variability of asthma and highlight the importance of
      periodic assessment of asthma control. These guidelines update recommendations
      for step-wise asthma treatment, address the burgeoning field of asthma
      diagnostics, and stress the importance of a patient and health care professional
      partnership, including written action plans and self monitoring. The field of
      asthma therapeutics is expanding rapidly, with promising new treatment options
      available or in development that may address some of the existing barriers to
      successful asthma management. These approaches simplify treatment, use
      combinations of agents in one delivery device that have complementary actions, or
      target specific pathways involved in asthma patho-physiology. Considerable
      activity is taking place in asthma pharmacogenetics. This review provides an
      overview of these new approaches to managing asthma, including their present
      status and future potential.

PMID- 18728854
TI  - Moderate and severe plaque psoriasis: cost-of-illness study in Italy.
AB  - Psoriasis is a chronic inflammatory, immune-mediated skin disorder that affects
      1.5-1.8 million people in Italy. The most common form of the disease is chronic
      plaque psoriasis, affecting about 90% of psoriasis patients, with about 20%-30%
      of them suffering from a moderate or severe condition. Little information is
      available about the economic impact of psoriasis in European countries. The
      primary objective of this study was to perform a cost-of-illness analysis of
      patients with moderate and severe plaque psoriasis in Italy. Therefore, direct,
      indirect costs, and intangible costs (quality of life - QoL) were assessed. In
      this national, multicenter, prospective, 3-month cost-of-illness study of
      moderate and severe plaque psoriasis, direct and indirect costs were assessed
      from the patient, third-party payer (National Health Service, NHS), and societal
      perspectives. From November 2003 to October 2004 consecutive patients were
      enrolled over a 1-year period, in order to minimize seasonal fluctuations in
      disease severity. 150 patients enrolled in 6 investigational sites in Italy,
      completed the study, and were eligible to be analyzed according to the study
      protocol. Intangible costs (QoL) were measured using SF36 and DLQI
      questionnaires. The mean total cost for psoriasis (average Psoriasis Area
      Severity Index [PASI] score 21.4), including direct and indirect items, was
      euro8,371.61 per patient per year. The mean cost for patients with moderate
      disease (PASI </= 20) was euro5,226.04, while the mean cost for patients with
      more severe disease (PASI > 20) was euro11,434.40 per year. Disease heavily
      affected QoL measured using SF36, and the impairment was greater in patients
      affected by a more severe form of disease. Moderate and severe plaque psoriasis
      is associated with extremely high costs, which are related to disease severity.
      Data from this study show that the more severe plaque psoriasis, the higher the
      direct and indirect costs for its management. Direct costs are higher than
      indirect costs; hospitalization represents the most significant item, accounting
      for 30% of the total expenses. QoL in moderate and severe plaque psoriasis is low
      compared with the population at large, confirming the high impact of plaque
      psoriasis on QoL. The relatively high average annual costs per patient point to
      the need for a more efficient and long-term control of psoriasis.

PMID- 18728855
TI  - New treatment options in allergic rhinitis: patient considerations and the role
      of ciclesonide.
AB  - Allergic rhinitis (AR) is a chronic inflammatory respiratory disease affecting 5%
      50% of the worldwide population and its prevalence is increasing (Herman 2007).
      In addition, AR is associated with asthma and other co-morbidities such as
      conjunctivitis and sinusitis. The main symptoms are nasal congestion, rhinorrea,
      sneezing, itching, and post-nasal drainage induced after allergen exposure by an
      IgE-mediated inflammation of the membranes lining the nose. AR is not a life
      threatening disease, but it has been shown to have a significant impact on
      quality of life. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines
      propose a classification of AR in intermittent and persistent, each graded as
      mild or moderate-severe, and provide a stepwise approach to the treatment.
      Inhaled steroids and antihistamine are the main tools in AR therapy but more safe
      and effective drugs are, however, needed. Inhaled steroid ciclesonide appears to
      be safe and effective.

PMID- 18728849
TI  - Update on local anesthetics: focus on levobupivacaine.
AB  - In recent years levobupivacaine, the pure S (-)-enantiomer of bupivacaine,
      emerged as a safer alternative for regional anesthesia than its racemic parent.
      It demonstrated less affinity and strength of depressant effects onto myocardial
      and central nervous vital centers in pharmacodynamic studies, and a superior
      pharmacokinetic profile. Clinically, levobupivacaine is well tolerated in a
      variety of regional anesthesia techniques both after bolus administration and
      continuous postoperative infusion. Reports of toxicity with levobupivacaine are
      scarce and occasional toxic symptoms are usually reversible with minimal
      treatment with no fatal outcome. Yet, levobupivacaine has not entirely replaced
      bupivacaine in clinical practice. In anesthesia and analgesia practice,
      levobupivacaine and bupivacaine produce comparable surgical sensory block with
      similar adverse side effects, and equal labor pain control with comparable
      maternal and fetal outcome. The equipotency of the two drugs has been recently
      questioned, prompting clinicians to increase the dose of levobupivacaine in an
      attempt to ensure adequate anesthesia and analgesia and offsetting, therefore,
      the advantages of less motor block with levobupivacaine. In this review we aim to
      discuss the pharmacological essentials of the safer profile of levobupivacaine,
      and analyze the evidence regarding the current clinical indications.

PMID- 18728863
TI  - The photodecomposition mechanism of tert-butyl-9-methylfluorene-9-percarboxylate:
      new insight from femtosecond IR spectroscopy.
AB  - The ultrafast photodissociation of tert-butyl-9-methylfluorene-9-percarboxylate
      (TBFC) is studied by mid-infrared transient absorption spectroscopy after UV
      excitation at 266 nm. By means of 13C-labeled TBFC and additional DFT
      calculations transient IR bands in the fingerprint region were unambiguously
      assigned to the methylfluorenyl radical. The experiments show that the
      fragmentation is controlled by the S1-lifetime of TBFC and, dependent on the
      solvent, within 0.8-2.1 ps leads to tert-butyloxy and methylfluorenyl radicals
      plus CO2 via concerted bond breakage of the O-O and the fluorenyl-C(carbonyl)
      bond. In accordance, the CO2 quantum yield is determined to be unity.

PMID- 18728861
TI  - BEP relations for N2 dissociation over stepped transition metal and alloy
      surfaces.
AB  - We present density functional theory (DFT) calculations for N2 dissociation on
      stepped face-centred cubic (211) surface slabs. By using the same crystal
      structure, the same adsorption site for atomic nitrogen, and the same transition
      state bond length of N2 over a range of pure metal surfaces, a perfectly linear
      Bronsted-Evans-Polanyi (BEP) relation between the transition-state potential
      energy and the dissociative chemisorption energy is obtained. The perfect BEP
      relation, which extends over 12 eV in chemisorption energy, suggests that the
      manifestation of BEP relations for surface reactions is a general electronic
      structure effect, and that geometric effects are responsible for the scatter
      which is normally observed around the BEP line. The BEP relation is also shown to
      be valid for both surface and bulk alloys. The scatter is, however, larger than
      for the pure elements. This can be understood as a larger geometrical variance.
      To analyze the accuracy of the DFT calculations a detailed convergence study is
      performed for several adsorbates on stepped hexagonal close-packed and face
      centred cubic Ru slabs.

PMID- 18728865
TI  - A dramatic difference between the electron-driven dissociation of alcohols and
      ethers and its relation to Rydberg states.
AB  - A difference was observed in the reactivity of alcohols and ethers toward free
      electrons. Whereas the lowest core-excited state of the negative ion-a 2(n,3s2)
      Feshbach resonance-of the alcohols readily dissociates by losing a hydrogen atom,
      ethers show no observable signal from this resonance. This difference in
      reactivity has a parallel in the anomalous shapes and energies of the parent
      states of the Feshbach resonances, the 1(n,3s) Rydberg states of the neutral
      alcohols. We explained this anomaly using potential surfaces of the alcohols and
      ethers calculated using the TD-DFT method as a function of the dissociation
      coordinate. The lowest excited state of alcohols was found to be repulsive,
      whereas a barrier to dissociation was found in the ethers. Rydberg-valence mixing
      and avoided crossings are decisive in determining the shapes of the potential
      surfaces. It is concluded that the reactivities of alcohols and ethers toward
      free electrons are rationalized by assuming that the potential surfaces of the
      daughter Feshbach resonances closely follow those of the parent Rydberg states,
      i.e., the lowest Feshbach resonance is repulsive, but a barrier occurs in ethers.
      The potential surfaces of both the Rydberg states and the Feshbach resonances
      thus differ dramatically from the non-dissociative surface of the grandparent
      2(n(-1)) positive ions, despite the nominally non-bonding character of the
      Rydberg electrons.

PMID- 18728866
TI  - Acidity constants from vertical energy gaps: density functional theory based
      molecular dynamics implementation.
AB  - The question of how to compute acidity constants (pKa) treating solvent and
      solute at the same level of theory remains of some interest, for example in the
      case of high or low pH conditions. We have developed a density functional theory
      based molecular dynamics implementation of such a method. The method is based on
      a half reaction scheme computing free energies of dissociation from the vertical
      energy gaps for insertion or removal of protons. Finite system size effects are
      important, but largely cancel when half reactions are combined to full reactions.
      We verified the method by investigating a series of organic and inorganic acids
      and bases spanning a wide range of pKa values (20 units). We find that the
      response of the aqueous solvent to vertical protonation/deprotonation is almost
      always asymmetric and correlated with the strength of the hydrogen bonding of the
      deprotonated base. We interpret these observations in analogy with the picture of
      solvent response to electronic ionization.

PMID- 18728862
TI  - Developing paradigms of chemical bonding: adaptive natural density partitioning.
AB  - A method of description of the chemical bonding combining the compactness and
      intuitive simplicity of Lewis theory with the flexibility and generality of
      canonical molecular orbital theory is presented, which is called adaptive natural
      density partitioning. The objects of chemical bonding in this method are n-center
      2-electron bonds, where n goes from one (lone-pair) to the maximum number of
      atoms in the system (completely delocalized bonding). The algorithm is a
      generalization of the natural bonding orbital analysis and is based on the
      diagonalization of the blocks of the first-order density matrix in the basis of
      natural atomic orbitals. The results obtained by the application of the algorithm
      to the systems with non-classical bonding can be readily interpreted from the
      point of view of aromaticity/antiaromaticity concepts. The considered examples
      include Li4 cluster and a family of planar boron clusters observed in molecular
      beams.

PMID- 18728867
TI  - Dynamics of the dispersion interaction in an energy transfer system.
AB  - On the propagation of resonant radiation through an optically dense system,
      photon capture is commonly followed by one or more near-field transfers of the
      resulting optical excitation. The process invokes secondary changes to the local
      electronic environment, shifting the electromagnetic interactions between
      participant chromophores and producing modified intermolecular forces. From the
      theory it emerges that energy transfer, when it occurs between chromophores with
      electronically dissimilar properties, can itself generate significant changes in
      the intermolecular potentials. This report highlights specific effects that can
      be anticipated when laser light propagates across an interface between
      differentially absorbing components in a model energy transfer system.

PMID- 18728873
TI  - Comprehensive theory for star-like polymer micelles; combining classical
      nucleation and polymer brush theory.
AB  - A comprehensive theory is proposed that combines classical nucleation and polymer
      brush theory to describe star-like polymer micelles. With a minimum of adjustable
      parameters, the model predicts properties such as critical micelle concentrations
      and micellar size distributions. The validity of the present theory is evidenced
      in direct comparison to experiments; this revealed that the proportionality
      constant in the Daoud-Cotton model is of the order of unity and that the star
      limit is valid down to relatively short corona chains. Furthermore, we show that
      the predicted saddle points in the free energy correspond to those solutions that
      are accessible with self-consistent field methods for self-assembly.

PMID- 18728864
TI  - Electron transport through carbon nanotube intramolecular heterojunctions with
      peptide linkages.
AB  - We present a systematic analysis of electron transport characteristics of carbon
      nanotube (CNT) intramolecular heterojunctions with peptide linkages, MM, SS, SM1,
      and SM2 where M and S stand for metallic and semiconducting CNT electrodes,
      respectively. Our theoretical investigations show that the incorporation of
      peptide linkages and their associated dipole moments play an important role in
      determining the electron transport characteristics and lead to materials with
      unique properties, such as Schottky-like behavior. Furthermore, we show that the
      Schottky-like behavior is observed in our SM1 junction but not in the SM2
      junction because of the different effects that arise from both the direction and
      strength of their dipole moments. We believe that our results will pave the way
      towards the design and implementation of various electronic logic functions based
      on carbon nanotubes for applications in the field of nanoelectronics.

PMID- 18728868
TI  - Water expansion dynamics after pulsed IR laser heating.
AB  - A nanosecond pulsed IR (1.9 microm) laser rapidly heated water, in an open
      vessel, to temperatures well below the boiling point. The subsequent dynamics of
      volume expansion were monitored using time-resolved interferometry in order to
      measure the increase in the water level in the heated area. The water expanded at
      less than the speed of sound, taking just less than 100 ns to increase its height
      by approximately 500 nm at surface temperature jumps of 20 K. The initial
      expansion was followed by an apparent contraction and then a re-expansion. The
      first expansion phase occurred more slowly than the timescale for bulk H-bond re
      structuring of the water, as determined from vibrational bands in the Raman
      spectra, and represents the limit to the rate at which the overpressure caused by
      sudden heating can be released. The second phase of the expansion was caused by
      hydrodynamic effects and is accompanied by morphological changes resulting in
      light scattering as well as droplet spallation.

PMID- 18728870
TI  - Redox-linked protein dynamics of cytochrome c probed by time-resolved surface
      enhanced infrared absorption spectroscopy.
AB  - Time-resolved surface enhanced infrared absorption (SEIRA) spectroscopy is
      employed to analyse the dynamics of the protein structural changes coupled to the
      electron transfer process of immobilised cytochrome c (Cyt-c). Upon electrostatic
      binding of Cyt-c to Au electrodes coated with self-assembled monolayers (SAMs) of
      carboxyl-terminated thiols, cyclic voltammetric measurements demonstrate a
      reversible redox process with a redox potential that is similar to that of Cyt-c
      in solution, and a non-exponential distance-dependence of the electron transfer
      rate as observed previously (D. H. Murgida and P. Hildebrandt, Chem. Soc. Rev.
      2008, 37, 937). On the basis of characteristic redox-state-sensitive amide I
      bands, the protein structural changes triggered by the electron transfer are
      monitored by rapid scan and step scan SEIRA spectroscopy in combination with the
      potential jump technique. Whereas the temporal evolution of the conjugate bands
      at 1693 and 1673 cm(-1) displays the same rate constants as electron transfer,
      the time-dependent changes of the 1660-cm(-1) band are slower by about a factor
      of 2. The study demonstrates that time-resolved SEIRA spectroscopy provides
      further information about the dynamics and mechanism of interfacial processes of
      redox proteins, thereby complementing the results obtained from other surface
      sensitive techniques. In comparison with previous surface enhanced resonance
      Raman spectroscopic findings, the present results are discussed in terms of the
      local electric field strengths at the Au/SAM/Cyt-c interface.

PMID- 18728875
TI  - Colorimetric response to mercury-induced abstraction of triethylene glycol
      ligands from a gold nanoparticle surface.
AB  - A simple method for specific colorimetric sensing of aqueous mercury(II) has been
      developed by using a gold nanoparticle supported by triethylene glycol ligand
      (Au:S-EG(3)). The unusual kinetic behavior of the sensing process of Hg(2+) and
      the TEM images of the Au core, as well as the electrospray ionization mass
      spectroscopic analysis of the analyte solution, have led us to propose a new
      color changing mechanism that involves ligand abstraction from a gold surface by
      Hg(2+).

PMID- 18728876
TI  - Surface spin glass behavior in sol-gel derived La0.7Ca0.3MnO3 nanotubes.
AB  - We report the fabrication of La(0.7)Ca(0.3)MnO(3) nanotubes (LCMONTs) with a
      diameter of about 200 nm, by a modified sol-gel method utilizing nanochannel
      alumina templates. High resolution transmission electron microscopy confirmed
      that the obtained LCMONTs are made up of nanoparticles (8-12 nm), which are
      randomly aligned in the wall of the nanotubes. The strong irreversibility between
      zero field cooling (ZFC) and field cooling (FC) magnetization curves as well as a
      cusplike peak in the ZFC curve gives strong support for surface spin glass
      behavior.

PMID- 18728872
TI  - Inclusion of 4-methoxy-2,2,6,6-tetramethylpiperidine-N-oxyl in a calixarene
      nanocapsule in the solid state.
AB  - We present an X-ray diffraction (XRD) and multi frequency electron spin resonance
      (ESR) study of the structure and dynamics of an inclusion complex of p-hexanoyl
      calix[4]arene (C6OH) with 4-methoxy-2,2,6,6-tetramethylpiperidine-N-oxyl (MT).
      The single crystal XRD experiments reveal that MT along with ethanol (solvent)
      molecules are entrapped in a capsular type crystalline lattice of the host C6OH
      material. ESR measurements were performed at 9.2 GHz/0.33 T (X-band) and at 360
      GHz/14 T. In order to avoid ESR line broadening resulting from electron dipole
      dipole interaction between nitroxides occupying neighbouring capsules in the
      crystal lattice, the capsules containing nitroxides were separated from each
      other by capsules containing diamagnetic dibenzylketone (DBK). Due to the
      extremely high g-tensor resolution of ESR at 360 GHz, we were able to
      distinguish, by shifts of their gxx component, between encapsulated nitroxide
      molecules forming a hydrogen bond between their O-(N) group and the OH group of
      an ethanol molecule occupying the same capsule and nitroxides missing this
      interaction. Temperature dependent ESR measurements revealed an orientational
      anisotropy in the motion of MT encapsulated in C6OH. Solid lipid nanoparticles
      (SLN) prepared from C6OH and loaded with the nitroxide retained the
      microcrystalline capsular structure of the pertinent inclusion complex. We found
      that encapsulated MT in SLNs becomes inaccessible to reducing agents such as
      sodium ascorbate.

PMID- 18728869
TI  - A spectroscopic study of self-assembled monolayer of porphyrin-functionalized
      oligo(phenyleneethynylene)s on gold: the influence of the anchor moiety.
AB  - Porphyrin-functionalized oligo(phenyleneethynylene)s (OPE) are promising
      molecules for molecular electronics applications. Three such molecules (1-3) with
      the common structure P-OPE-AG (P and AG are a porphyrin and anchor group,
      respectively) and different anchor groups, viz. an acetyl protected thiol, -S
      COCH3 (1), an acetyl protected thiol with methylene linker, -CH2-S-COCH3 (2), and
      a trimethylsilylethynyl group, -C(triple bond)C-Si(CH3)3 (3) have been
      synthesized and the corresponding self-assembled monolayers (SAMs) on Au(111)
      substrates have been prepared. The integrity and structural properties of these
      films were studied by X-ray photoelectron spectroscopy and near-edge X-ray
      absorption fine structure spectroscopy. The results suggest that the films formed
      from 1 have a high orientational order with an almost upright orientation and
      dense packing of the molecular constituents, i.e. represent a high quality SAM.
      In contrast, molecule 2 formed disordered molecular layers on Au, even though the
      molecule-surface bonding (thiolate) is the same as in the case of molecule 1.
      This suggests that the methylene linker in molecule 2 has a strong impact on the
      quality of the resulting film, so that a well-ordered SAM cannot be formed. The
      silane system, 3, is also able to bind to the gold surface but the resulting SAM
      has a poor quality, being significantly disordered and/or comprised of strongly
      inclined molecules. The above results suggest that the nature of the anchor group
      along with a possible linker is an important parameter which, to a high extent,
      predetermines the entire quality of OPE-based molecular layers.

PMID- 18728878
TI  - A lanthanide-based metal-organic framework with a dynamic porous property.
AB  - Hydrothermal reaction of La(NO(3))(3), NaHCO(3) and H(3)L (H(3)L = pyrazole-3,5
      dicarboxylic acid) gives a 3D metal-organic framework with a dynamic porous
      property.

PMID- 18728877
TI  - 1D, 2D and 3D luminescent zinc(II) coordination polymers assembled from varying
      flexible thioether ligands.
AB  - Using a series flexible thioether ligands, 4-(2-pyridylmethylthio)benzoic acid
      (HL(1)), 4-(4-pyridylmethylthio)benzoic acid (HL(2)) and 4-(3
      pyridylmethylthio)benzoic acid (HL(3)), a 1D infinite chain [Zn(3)(L(1))(6)](n)
      (1), a 2D interpenetrating sheet [Zn(L(2))(2)](n) (2), and a chiral 3D framework
      [Zn(L(3))(2)H(2)O](n) (3) were obtained. Luminescent properties of these
      compounds were also studied.

PMID- 18728874
TI  - Hydrogenated tetraazaporphyrins--old but new core-modified phthalocyanine
      analogues.
AB  - The synthesis, and spectroscopic and electrochemical properties of hydrogenated
      tetraazaporphyrins (TAPs), namely tetraazachlorins (TACs),
      tetraazabacteriochlorins (TABCs) and tetraazaisobacteriochlorins (TAiBCs), have
      been reviewed. While the first synthesis of this type of hydrogenated aromatic
      macrocycle was achieved as early as 1958 by Linstead et al. (G. E. Ficken, R. P.
      Linstead, E. Stephen and M. Whalley, J. Chem. Soc., 1958, 3879), the development
      of modern synthetic strategies enables us to isolate stable forms of the
      hydrogenated TAP derivatives. Benzo-, 2,3-naphtho- and 1,2-naphtho-fused
      derivatives were synthesized extensively, and all structural isomers have been
      elucidated. The chemical structures have been characterized using a variety of
      techniques, including mass spectrometry, (1)H and (13)C NMR, X-ray
      crystallography and IR spectroscopy. The spectroscopic properties (e.g.,
      electronic absorption, magnetic circular dichroism (MCD), and fluorescence) of
      these compounds differ significantly from those of the original TAPs, or
      phthalocyanines (Pcs), due to the symmetry-lowering effects of the core aromatic
      macrocycles. The experimentally observed properties have been rationalized on the
      basis of electrochemical studies and quantum chemical calculations. As an
      application of the TAC skeleton, the synthesis and electronic structures of
      tribenzo TAC (TBTAC)-C(60) conjugates, in which both components are covalently
      connected directly and thus show remarkable molecular orbital (MO) mixing between
      the constituting moieties, have also been reviewed.

PMID- 18728879
TI  - Revisiting the crystal structure and thermal properties of NaMgAl(oxalate)3 x 9
      H2O/Cr(III): an extraordinary spectral hole-burning material.
AB  - We have reinvestigated the crystal structure and thermal properties of
      NaMgAl(oxalate)(3) x 9 H(2)O. In the thermal gravimetric analysis the steps of
      dehydration and decomposition/oxidation yield a mass change that is commensurate
      with 9 water molecules of hydration. Dehydration steps occur at 127, 171, and 201
      degrees C whereas the oxalate ligand decomposes in steps at 403 and 424 degrees C
      with a final oxidation step at 692 degrees C. A refinement of the single crystal
      X-ray diffraction data taken at 200 K affirms the P3c1 space group with nine
      water molecules of hydration and unit cell parameters a = b = 16.7349(2) A and c
      = 12.6338(1) A with Z = 6. The structures can be described in terms of
      modulations of an idealised Z = 1 structure in P3lm. T-Cycle experiments of
      spectral holes in the R(1)-line yield a single Gaussian barrier with T(0) +/-
      sigma(T) of 46 +/- 21 K and three barriers with 40 +/- 12, 70 +/- 10, 107 +/- 5 K
      for perprotonated and partially deuterated (46%) NaMgAl(oxalate)(3) x 9
      H(2)O/Cr(III) 0.5%, respectively.

PMID- 18728871
TI  - A kinetic study of Ca-containing ions reacting with O, O2, CO2 and H2O:
      implications for calcium ion chemistry in the upper atmosphere.
AB  - A series of gas-phase reactions involving molecular Ca-containing ions was
      studied by the pulsed laser ablation of a calcite target to produce Ca+ in a fast
      flow of He, followed by the addition of reagents downstream and detection of ions
      by quadrupole mass spectrometry. Most of the reactions that were studied are
      important for describing the chemistry of meteor-ablated calcium in the earth's
      upper atmosphere. The following rate coefficients were measured: k(CaO+ + O -->
      Ca+ + O2) = (4.2 +/- 2.8) x 10(-11) at 197 K and (6.3 +/- 3.0) x 10(-11) at 294
      K; k(CaO+ + CO --> Ca+ + CO2, 294 K) = (2.8 +/- 1.5) x 10(-10); k(Ca+.CO2 + O2 -
      > CaO2+ + CO2, 294 K) = (1.2 +/- 0.5) x10(-10); k(Ca+.CO2 + H2O --> Ca+.H2O +
      CO2) = (13.0 +/- 4.0) x 10(-10); and k(Ca+.H2O + O2 --> CaO2+ + H2O, 294 K) =
      (4.0 +/- 2.5) x 10(-10) cm3 molecule(-1) s(-1). The quoted uncertainties are a
      combination of the 1 sigma standard errors in the kinetic data and the systematic
      errors in the models used to extract the rate coefficients. Rate coefficients
      were also obtained for the following recombination (also termed association)
      reactions in He bath gas: k(Ca+.CO2 + CO2 --> Ca+.(CO2)2, 294 K) = (2.6 +/- 1.0)
      x 10(-29); k(Ca+.H2O + H2O --> Ca+.(H2O)2) = (1.6 +/- 1.1) x 10(-27); and k(CaO2+
      + O2 --> CaO2+.O2) < 1 x 10(-31) cm6 molecule(-2) s(-1). These recombination rate
      coefficients, as well as those for the ligand-switching reactions listed above,
      were then interpreted using a combination of high level quantum chemistry
      calculations and RRKM theory using an inverse Laplace transform solution of the
      master equation. The surprisingly slow reaction between CaO+ and O was explained
      using quantum chemistry calculations on the lowest 2A', 2A'' and 4A'' potential
      energy surfaces. These calculations indicate that reaction mostly occurs on the
      2A' surface, leading to production of Ca+ (2S) + O2(1 Delta g). The importance of
      this reaction for controlling the lifetime of Ca+ in the upper mesosphere and
      lower thermosphere is then discussed.

PMID- 18728882
TI  - Superbulky metallocene complexes of the heavier alkaline-earth metals strontium
      and barium.
AB  - Superbulky sandwich complexes with the cyclopentadienyl ligand (4-nBu
      C(6)H(4))(5)Cp (abbreviated here as Cp(BIG)) have been prepared by reaction of
      Cp(BIG)H with benzylic strontium or barium reagents. Both metallocenes have been
      structurally characterized by single crystal X-ray diffraction. Even for the
      larger metallocene (Cp(BIG))(2)Ba a highly symmetric sandwich complex with
      parallel Cp rings was isolated (Cp(center)-Ba = 2.667(1) A). Both structures show
      evidence for a C-HC(pi) network between the Cp ligands. These attractive forces
      induce an inward out-of-plane bending of the aryl substituents (Sr 3.4(2)
      degrees; Ba 5.3(2) degrees). A linear correlation between this bending angle and
      metal size has been found.

PMID- 18728885
TI  - Luminescence properties of Pt(II) complexes containing polypyridine ligands with
      extended aromatic moieties.
AB  - The luminescence properties of eleven Pt(II) complexes containing polypyridine
      ligands with extended aromatic moieties have been studied, both in acetonitrile
      fluid solution at 298 K and in butyronitrile rigid matrix at 77 K. For comparison
      purposes, also the phosphorescence properties of three free ligands at 77 K in
      butyronitrile have been investigated. The absorption spectra of all the compounds
      exhibit intense bands (epsilon in the range 10(4)-10(5) M(-1) cm(-1)) in the UV
      region, which are attributed to spin-allowed ligand-centered (LC) transitions,
      and moderately intense bands (epsilon in the range 10(3)-10(4) M(-1) cm(-1)) in
      the visible region, which receive contribution from both spin-allowed LC
      transitions and spin-allowed metal-to-ligand charge-transfer (MLCT) transitions.
      At low energy, less intense spin-forbidden MLCT bands are also present. At 77 K
      in rigid matrix, all the studied compounds exhibit structured and long-lived
      (lifetimes from 840 micros on the millisecond timescale) luminescence, which is
      attributed to triplet LC states in all cases. At room temperature in fluid
      solution the luminescence lifetime of all the compounds is largely shortened
      (nanosecond timescale), and most of the emission spectra are unstructured and red
      shifted. For species exhibiting structured emission spectra even at room
      temperature, low luminescence quantum yields are always obtained (Phi < 10(4)),
      and their emission is assigned to triplet LC states, which mainly deactivate to
      the ground state by thermal-activated surface crossing to a closely-lying metal
      centered (MC) triplet state. Compounds exhibiting unstructured emission show
      relatively high emission quantum yields (about 0.1) and their emission is
      assigned to a mixed LC/MLCT state.

PMID- 18728889
TI  - Synthesis and structural characterization of four new organically-directed
      bismuth sulfates.
AB  - Four new organically-directed bismuth sulfates,
      (C(2)N(2)H(10))(3)[Bi(2)(SO(4))(6)(H(2)O)(2)] x 4 H(2)O (I),
      (C(5)N(2)H(14))[Bi(SO(4))(2)(HSO(4))(H(2)O)] x H(2)O (II),
      (C(4)N(3)H(16))[Bi(SO(4))(3)(H(2)O)] (III) and
      (C(6)N(4)H(22))[Bi(2)(SO(4))(5)(H(2)O)(2)] x 4 H(2)O (IV) have been synthesized
      and structurally characterized by single-crystal X-ray diffraction analysis. Four
      compounds were constructed from strictly alternating BiO(n) and SO(4) polyhedra.
      I and II both exhibit similar infinite courrgated anionic layers with 8-membered
      ring windows, III shows a new 1D ladder-like chain containing 4-membered rings,
      while IV possesses a new flat layer with 12-membered ring windows. The diverse
      linking fashions of the five-connected Bi nodes and the mono-, bi- or tri
      connected S nodes form unique Bi-S-Bi topologies. Their fluorescent properties
      are also reported.

PMID- 18728884
TI  - Ni(II) complexes featuring non-metallated pincer-type ligands.
AB  - Attempts to prepare pincer-type Ni complexes from the ligands (i
      Pr(2)POCH(2))(2)CH(2) and (pz*CH(2))(2)CH(2) (pz* = 3,5-dimethylpyrazol-1-yl)
      gave instead the complexes cis-{kappa(P),kappa(P')-(i
      Pr(2)POCH(2))(2)CH(2)}NiCl(2) and {kappa(N),kappa(N')-(pz*CH(2))(2)CH(2)}NiBr(2).
      X-Ray diffraction studies confirmed that these potentially pincer-type ligands
      have not undergone metallation, serving instead as chelating ligands in
      essentially square-planar or tetrahedral complexes. Heating of these compounds
      failed to induce metallation of the coordinated ligands.

PMID- 18728880
TI  - Biphenylamide ligand complexes of Li and Al: hemilabile arene donors?
AB  - Biphenylamide ligands were employed to prepare a series of Li and Al derivatives
      in which the ligand binds through N. Such species include: (2-C(6)H(4)Ph)Bu(t)NLi
      (3), (2-C(6)H(4)Ph)Bu(t)NLi(THF)(2) (4), (2-C(6)H(4)Ph)Bu(t)NLi.OEt(2) (5), [(mu
      (2-C(6)H(4)Ph)(2)N)Li](2) (6), (2-C(6)H(4)Ph)(2)NLi(THF)(2) (7), (2
      C(6)H(4)Ph)(2)NLi.OEt(2) (8) amd (2-C(6)H(4)Ph)(2)NAlX(2) (X = Cl (9), Me (10),
      Et (11)). Structural and spectroscopic data show that these species exhibit weak
      arene to metal donation. This donor is hemilabile being readily displaced by
      other stronger donors to give such species as (2-C(6)H(4)Ph)(2)NAlMe(2)(THF) (12)
      and (2-C(6)H(4)Ph)(2)NAlMe(2)(CH(2)PPh(3)) (13). Reactions of 10 with
      B(C(6)F(5))(3) results in methyl for C(6)F(5) exchange and isolation of (2
      C(6)H(4)Ph)(2)NAl(C(6)F(5))(2) (14). The presence the electron withdrawing groups
      in 14 further strengthens the hemilabile interaction.

PMID- 18728887
TI  - Ten-vertex polyhedral azametallaborane chemistry: a unique nido-6,9 to nido-6,8
      cluster isomerization.
AB  - Reaction of the [arachno-4-NB(8)H(12)](-) anion 2 with [RhCl(2)(eta(5)
      C(5)Me(5))](2) in CH(2)Cl(2) at room temperature affords a mixture of red '6,9'
      isomer [9-(eta(5)-C(5)Me(5))-nido-6,9-NRhB(8)H(11)] (3) and its yellow '6,8'
      isomer, [8-(eta(5)-C(5)Me(5))-nido-6,8-NRhB(8)H(11)] (4). Under the same
      conditions, reactions of 2 with [IrCl(2)(eta(5)-C(5)Me(5))](2) and
      [RuCl(2)(eta(6)-MeC(6)H(4)-4-(iso)Pr)](2) give the '6,8' isomers, yellow [8
      (eta(5)-C(5)Me(5))-nido-6,8-NIrB(8)H(11)] (5) and red [8-(eta(6)-MeC(6)H(4)-4
      (iso)Pr)-nido-6,8-NRuB(8)H(11)] (6), respectively. In contrast, [IrCl(PPh(3))(3)]
      yields orange [9,9-(PPh(3))(2)-9-H-nido-6,9-NIrB(8)H(11)] (7), which exhibits the
      '6,9' configuration. Compound 3 isomerizes quantitatively in solution to give 4.
      At high temperatures, compound 7 gives the yellow '6,8' species, [8,8-(PPh(3))(2)
      8-H-nido-6,8-NIrB(8)H(11)] (8), in low yields. Possible mechanisms for the
      unprecedented 6,9 --> 6,8 isomerization are discussed.

PMID- 18728891
TI  - Beyond the metal-metal triple bond in binuclear cyclopentadienylchromium carbonyl
      chemistry.
AB  - The cyclopentadienylchromium carbonyls Cp(2)Cr(2)(CO)(n) and Cp*(2)Cr(2)(CO)(n)
      (Cp = eta(5)-C(5)H(5) and Cp* = eta(5)-Me(5)C(5); n = 3, 2) have been studied by
      density functional theory using the B3LYP and BP86 functionals. Triplet and
      singlet structures are found for Cp(2)Cr(2)(CO)(3), with the triplet isomer
      having an apparent Cr[triple bond]Cr triple bond (2.295 A by BP86) and predicted
      to have a lower energy than the singlet isomer having an apparent Cr[quadruple
      bond]Cr quadruple bond (2.191 A by BP86). Quintet, septet, and singlet
      structures, as well as a highly spin contaminated triplet structure, were found
      for the dicarbonyl Cp(2)Cr(2)(CO)(2). In all of the Cp(2)Cr(2)(CO)(n) (n = 3, 2)
      structures the carbonyls are asymmetric semi-bridging groups, typically with
      differences of 0.3-0.5 A between the shortest and longest M-C distances. Very
      little difference was found between the structures and energetics of the
      corresponding Cp and Cp* derivatives. These DFT studies suggest that the reported
      unstable photolytic decarbonylation product of Cp*(2)Cr(2)(CO)(4), characterized
      only by its infrared nu(CO) frequencies, is the singlet isomer of the tricarbonyl
      Cp*(2)Cr(2)(CO)(3).

PMID- 18728881
TI  - Study on a set of bis-cyclometalated Ir(III) complexes with a common ancillary
      ligand.
AB  - Bis-cyclometalated iridium(III) complexes [Ir(F2ppy)2ZN] (FZN), [Ir(F2CNppy)2ZN]
      (FCZN), [Ir(DMAF2ppy)2ZN] (FDZN) and [Ir(MeOF2ppy)2ZN] (MeOFZN) (F2ppy = 4',6'
      difluoro-2-phenylpyridinate, F2CNppy = 5-cyano-4',6'-difluoro-2-phenylpyridinate,
      DMAF2ppy = 4',6'-difluoro-4-dimethylamino-2-phenylpyridinate, MeOF2ppy = 4',6'
      difluoro-4-methyl-2-phenylpyridinate and ZN = 3,5-dimethylpyrazole-N-carboxamide)
      emitting in the sky blue region were synthesized. We studied the effect of the
      ancillary ligand ZN and the substituents on the cyclometalating ligands on the
      crystal structures, photophysical and electrochemical properties and the frontier
      orbitals. Density functional theory (DFT) calculation results indicate that in
      FCZN and FDZN the cyclometalating ligands show negligible participation in the
      HOMO, the ancillary ligand ZN being the main participant along with the Ir(III) d
      orbitals. MeOFZN exhibits the maximum photoluminescence quantum efficiency and
      radiative emission rates along with the dominant low frequency metal-ligand
      vibrations and maximum reorganization energy in the excited state. All the
      substituted complexes show more polar characteristics than FZN, FCZN possessing
      the highest dipole moment among the complexes. The performances of the solution
      synthesised organic light emitting devices (OLEDs) of FZN, FCZN and FDZN doped in
      a blend of mCP (m-bis(N-carbazolylbenzene)) and polystyrene are studied.

PMID- 18728883
TI  - pH-Dependent isotope exchange and hydrogenation catalysed by water-soluble NiRu
      complexes as functional models for [NiFe]hydrogenases.
AB  - The pH-dependent hydrogen isotope exchange reaction between gaseous isotopes and
      medium isotopes and hydrogenation of the carbonyl compounds have been
      investigated with water-soluble bis(mu-thiolate)(mu-hydride)NiRu complexes,
      Ni(II)(mu-SR)(2)(mu-H)Ru(II) {(mu-SR)(2) = N,N'-dimethyl-N,N'-bis(2
      mercaptoethyl)-1,3-propanediamine}, as functional models for [NiFe]hydrogenases.
      In acidic media (at pH 4-6), the mu-H ligand of the Ni(II)(mu-SR)(2)(mu-H)Ru(II)
      complexes has H(+) properties, and the complexes catalyse the hydrogen isotope
      exchange reaction between gaseous isotopes and medium isotopes. A mechanism of
      the hydrogen isotope exchange reaction between gaseous isotopes and medium
      isotopes through a low-valent Ni(I)(mu-SR)(2)Ru(I) complex is proposed. In
      contrast, in neutral-basic media (at pH 7-10), the mu-H ligand of the Ni(II)(mu
      SR)(2)(mu-H)Ru(II) complexes acts as H(-), and the complexes catalyse the
      hydrogenation of carbonyl compounds.

PMID- 18728886
TI  - A new class of functionalized polyoxometalates: synthesis, structure and
      preliminary antitumor activity studies of three arylimido substituted
      hexamolybdates bearing a strong electron-withdrawing nitro group,
      (Bu4N)2[Mo6O18([triple bond]NAr)] (Ar = 3-NO2-C6H4, 2-CH3-4-NO2-C6H3, 2-CH3-5-NO2
      C6H3).
AB  - Three novel mono-functionalized arylimido derivatives of hexamolybdate bearing
      the strongest electron-withdrawing nitro group, (Bu(4)N)(2)[Mo(6)O(18)([triple
      bond]NAr)] (1, 2 and 3), have been synthesized for the first time by an improved
      reaction of octamolybdate ion and 3-nitroaniline hydrochloride, 2-methyl-4
      nitroaniline hydrochloride and 2-methyl-5-nitroaniline hydrochloride respectively
      with DCC (N,N'-dicyclohexylcarbodiimide) as a dehydrating agent. Complete
      assignments were achieved for the title compounds by elemental analysis, IR, (1)H
      NMR, UV/visible and single-crystal X-ray diffraction analyses. The preliminary
      antitumor activity test indicated that the title compounds have some effects on
      the cellular growth inhibition of K562 cells.

PMID- 18728890
TI  - Flexible coordination of bulky amidinates and guanidinates towards rhodium(I):
      conversion of kinetic to thermodymanic isomers.
AB  - Reactions of the bulky amidinate and guanidinate salts K[(ArN)(2)CR] (R = Bu(t),
      NPr(i)(2) or N(C(6)H(11))(2); Ar = 2,6-diisopropylphenyl) with [{RhCl(eta(4)
      COD)}(2)] (COD = 1,5-cyclooctadiene) lead to KCl elimination and the formation of
      the complexes, [Rh{(eta(5)-ArN)(ArN)CR}(COD)], in which the anionic ligand
      coordinates the rhodium centre in an unprecedented eta(5)-cyclohexadienyl mode.
      The thermal conversions of these complexes to their N,N'-chelated isomers,
      [Rh{kappa(2)-N,N'-(ArN)(2)CR}(COD)], were carried out and the kinetics of these
      processes have been shown to be first order. The rates of the isomerisations are
      inversely proportional to the size of the amidinate or guanidinate backbone
      substituent. Analogies between the ligating properties of the bulky amidinates
      and guanidinates used in the study, and those of beta-diketiminates are
      discussed.

PMID- 18728895
TI  - An investigation into the origins of a series of PM10 anomalies at a remote
      location in NW England.
AB  - Throughout 2004, PM(10) concentrations were measured at 10 min intervals at
      Hazelrigg, a remote location in NW England. The annual mean concentration was 6.1
      microg m(-3) and likely origins were determined using directional and particle
      size characteristics. The fine temporal resolution of the monitoring also allowed
      several short periods (< 20 h) of persistently high PM(10) concentration to be
      identified and then 'typed' by event start time, duration, wind direction and
      particle size characteristics. A series of night time PM(10) anomalies
      (concentration < 465 microg m(-3)) of no obvious source were identified, and by
      elimination assumed to have originated from a ground-based fire of particle-rich
      fodder. A novel methodology combining Stokes' Law with systematic and rigorous
      modelling of source strength (using ADMS3.2) was developed to locate a possible
      burn site. The process was limited by the lack of previous modelling studies
      related to ground-based fires, and also by the capacity of ADMS3.2 to model sub
      hourly time-varying emissions and fluctuations in wind speed and direction in the
      near field. However, modelling did suggest the source was located <400 m SSE of
      Hazelrigg, and investigation of this area revealed a burn site where tyres and
      plastic bags were piled nearby. Few studies have combined directional analysis
      and modelling to locate a source based on sampled data. This innovative
      methodology could be used by regulatory bodies to investigate the origins of
      unidentified PM(10) observed within the particle record.

PMID- 18728899
TI  - Investigation of transcription-mediated amplification as a rapid test method for
      Enterococci in recreational water.
AB  - Growth-based methods for detecting faecal contamination of recreational water
      require at least 24 hours to yield results, which can delay detection, action and
      remediation, if required. Such delays can put human health at risk while closing
      beaches inappropriately can cause unnecessary economic losses. There is a
      requirement for more rapid methods to facilitate the management of pollution
      events. In this study, undertaken in our respective laboratories, a molecular
      assay based on transcription-mediated amplification (TMA) technology was compared
      with established growth-based methods. The assays were used to quantitate
      enterococcal faecal indicator bacteria (relative to the legislative threshold of
      104 colony forming units/100 mL) in 138 water samples collected from 41 different
      locations, representative of different recreational water types routinely sampled
      in Southern California. The results demonstrate the efficacy of the TMA assay for
      the detection of Enterococcus species in recreational water as a rapid
      alternative to traditional methods.

PMID- 18728897
TI  - The equivalence of diffusive samplers to reference methods for monitoring O3,
      benzene and NO2 in ambient air.
AB  - A study of the equivalence to the reference methods of the Radiello samplers for
      ozone (O(3)) and benzene as well as the membrane-closed Palmes tube (MCPT) for
      nitrogen dioxide (NO(2)) is presented. These samplers benefit from new model
      equations capable of estimating their uptake rate. For O(3), the aim here was to
      demonstrate the equivalence for the reference period of 8 h and 120 microg m(-3),
      the target value of the 3rd European Daughter Directive. For benzene, the
      demonstration of equivalence to the annual limit value of 5 microg m(-3) of the
      2nd European Daughter Directive was examined. In the case of NO(2), the
      equivalence to the annual limit value of the 1st European Daughter Directive (40
      microg m(-3)) was considered. Results show that the radial sampler for O(3) fails
      to meet the Data Quality Objective (DQO) for continuous monitoring. However, with
      an expanded uncertainty of less than 30%, the O(3) diffusive sampler fulfils the
      DQO for indicative measurements. For benzene, the Radiello sampler exposed for 7
      days gave satisfying results showing the ability of the sampler to meet the DQO
      of the reference method. Nevertheless, the field tests should be complemented by
      measurements for a wider range of benzene concentrations. In the case of NO(2),
      all the results of the laboratory and field experiments respected the
      requirements necessary for the demonstration of equivalence. Overall, these
      findings thus show that the Radiello sampler and the MCPT are equivalent to the
      reference methods only for assessment of benzene and NO(2), respectively.

PMID- 18728898
TI  - The effect of the number of counted traverses on the estimation of the total
      spore count sampled on a non-cultivable slit impactor.
AB  - Various counting rules are used for spore trap analysis. Partial count can lead
      to concentration errors. This paper demonstrates that the number of traverses
      counted affects the final results.

PMID- 18728904
TI  - Metal remediation from partially composted distillery sludge using composting
      earthworm Eisenia fetida.
AB  - Distillery sludge, a sugar industry byproduct, has been recommended widely as a
      potential soil conditioner, but high concentrations of metals limit its
      continuous use for field crops. In this study we tested the feasibility of
      earthworm Eisenia fetida (Savigny) in removing metals (Fe, Cu, Zn, Pb) from
      sludge through vermitechnology. The transfer of metals during the vermicomposting
      process was also estimate in terms of total metal contents in vermicomposted
      sludge and earthworm tissues. The sludge processed by worms showed a significant
      reduction in concentration of metals: Zn (20.5-43.8%), Fe (23.6-34.0%), Mn (18.0
      45.7%) and Cu (29.0-58.1%), at the end. The metal reduction in sludge was
      directly related to the bioaccumulation of metals in the tissues of composting
      earthworms. The inoculated earthworms showed a considerable level (dry wt basis)
      of Zn (103.7-143.3 mg kg(-1)), Fe (87.2-146.5 mg kg(-1)), Mn (83.7-138.6 mg kg(
      1)) and Cu (16.8-25.5 mg kg(-1)) in their tissues. A higher range of
      bioconcentration factors (BCFs) for different metals studied further suggest the
      candidature of earthworm to be used effectively for removal of metals form
      industrial sludges. The obtained vermicomposts form different vermireactors were
      rich in nutrients. The feasibility of earthworms to mitigate the metal toxicity
      and to enhance the nutrient profile in sludge might be useful in sustainable land
      restoration practices at low-input basis. The ranges of metals in end product
      were within the standards recommended by different agencies.

PMID- 18728888
TI  - Synthesis, structures and catalytic properties of iron(III) complexes with
      asymmetric N-capped tripodal NO3 ligands and a pentadentate N2O3 ligand.
AB  - A new family of N-capped tripodal NO(3) proligands N,N-bis(2-hydroxy-3,5-di-tert
      butylbenzyl)-N-(2'-hydroxy-5'-R-phenyl)amine [H(3)(L(n))] [when R= Me, n = 1; R=
      (t)Bu, n = 2; R = Cl, n = 3] with different substituents in one of the aryl rings
      and N,N-bis(2-hydroxy-3-tert-butylbenzyl)-N-(2'-hydroxy-5'-methylphenyl)amine
      [H(3)(L(4))] were synthesised. The preparation of a new pentadentate proligand N
      methyl-N,N',N'-tris(2-hydroxy-3,5-di-tert-butylbenzyl)ethane-1,2-diamine
      [H(3)(L(5))] with an N(2)O(3) donor set is also reported. Reaction of the
      proligands [H(3)(L(n))] (n = 1-4) with iron(III) chloride in the presence of base
      (triethylamine) and 1-methylimidazole (1-Meim) as co-ligand led to the formation
      of iron complexes of the type [Fe(L(n))(1-Meim)] (n = 1-4) (1-4) respectively,
      while treatment of the trilithium salt of [H(3)(L(5))] with iron(III) chloride
      afforded [Fe(L(5))] (5). All complexes were structurally characterised by X-ray
      crystallography. In complexes 1-4, the ligands form five- and six-membered
      chelate rings with the iron centres which have distorted trigonal bipyramidal
      geometry with an N(2)O(3) coordination environment. Complex 5 adopts a similar
      distorted trigonal bipyramidal geometry also with N(2)O(3) coordination around
      the iron centre. The catalytic activity of these iron complexes towards
      epoxidation of styrene was examined.

PMID- 18728894
TI  - Regional and seasonal characteristics of emission sources of fine airborne
      particulate matter collected in the center and suburbs of Tokyo, Japan as
      determined by multielement analysis and source receptor models.
AB  - Airborne particulate matter, suspected to induce adverse effects on human health,
      have been one of the most important concerns regarding recent air pollution
      issues in Japan. To characterize regional and seasonal variations in emission
      sources of fine airborne particulate matter (d < 2 microm), monthly samples (n =
      36 for each site) were collected at urban (Tokyo), suburban (Maebashi), and
      mountainous (Akagi) sites in Japan from April 2003 to March 2006. Multielement
      analysis of chemical species (Na, Al, K, Ca, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Sb,
      and Pb) was performed by inductively coupled plasma-atomic emission spectrometry
      and inductively coupled plasma-mass spectrometry. The combined source receptor
      model, which consists of positive matrix factorization and chemical mass balance,
      determined the contributions of nine emission sources (local and continental
      soils, road dust, coal and oil combustion, waste incineration, steel industry,
      brake wear, and diesel exhaust) to the observed elemental concentrations. Large
      regional differences were identified in the source contributions among the
      observational sites. Diesel exhaust was identified as the most significant source
      (70% of identified contributions) at the urban site. Local and continental soils,
      coal combustion, and diesel exhaust were intricately assigned (20-30% each) to
      the suburban site. Continental soil was the predominant source (65%) at the
      mountainous site. Respective significant source contributions dominated the
      seasonal variations of total elemental concentrations at each site. These results
      suggest that a better understanding of the regional and seasonal characteristics
      of impacting emission sources will be important for improving regional
      environments.

PMID- 18728903
TI  - Metal release rate from AISI 316L stainless steel and pure Fe, Cr and Ni into a
      synthetic biological medium--a comparison.
AB  - Metal release rates from stainless steel grade 316L were investigated in
      artificial lysosomal fluid (ALF), simulating a human inflammatory cell response.
      The main focus was placed on release rates of main alloying elements using
      graphite furnace atomic absorption spectroscopy, and changes in surface oxide
      composition by means of X-ray photoelectron spectroscopy. To emphasise that
      alloys and pure metals possess totally different intrinsic properties,
      comparative studies were performed on the pure alloying constituents: iron,
      nickel and chromium. Significant differences in release rates were observed due
      to the presence of a passive surface film on stainless steel. Iron and nickel
      were released at rates more than 300 times lower from the 316L alloy compared
      with the pure metals whereas the release rate of chromium was similar. Iron was
      preferentially released compared with nickel and chromium. Immersion in ALF
      resulted in the gradual enrichment of chromium in the surface film, a small
      increase of nickel, and the reduction of oxidized iron with decreasing release
      rates of alloy constituents as a result. As expected, released metals from
      stainless steel grade 316L were neither in proportion to the bulk alloy
      composition nor to the surface film composition.

PMID- 18728902
TI  - Corrosion-induced release of the main alloying constituents of manganese-chromium
      stainless steels in different media.
AB  - The main focus of this paper is the assessment of release rates of chromium,
      nickel, iron and manganese from manganese-chromium stainless steel grades of low
      nickel content. The manganese content varied between 9.7 and 1.5 wt% and the
      corresponding nickel content between 1 and 5 wt%. All grades were exposed to
      artificial rain and two were immersed in a synthetic body fluid of similar pH but
      of different composition and exposure conditions. Surface compositional studies
      were performed using X-ray photoelectron spectroscopy (XPS) in parallel to
      correlate the metal release process with changes in surface oxide properties. All
      grades, independent of media, revealed a time-dependent metal release process
      with a preferential low release of iron and manganese compared to nickel and
      chromium while the chromium content of the surface oxide increased slightly.
      Manganese was detected in the surface oxide of all grades, except the grade of
      the lowest manganese bulk content. No nickel was observed in the outermost
      surface oxide. Stainless steel grades of the lowest chromium content
      (approximately 16 wt%) and highest manganese content (approximately 7-9 wt%),
      released the highest quantity of alloy constituents in total, and vice versa. No
      correlation was observed between the release rate of manganese and the alloy
      composition. Released main alloy constituents were neither proportional to the
      bulk alloy composition nor to the surface oxide composition.

PMID- 18728896
TI  - Ambient site, home outdoor and home indoor particulate concentrations as proxies
      of personal exposures.
AB  - Despite strong longitudinal associations between particle personal exposures and
      ambient concentrations, previous studies have found considerable inter-personal
      variability in these associations. Factors contributing to this inter-personal
      variability are important to identify in order to improve our ability to assess
      particulate exposures for individuals. This paper examines whether ambient, home
      outdoor and home indoor particle concentrations can be used as proxies of
      corresponding personal exposures. We explore the strength of the associations
      between personal, home indoor, home outdoor and central outdoor monitoring site
      ("ambient site") concentrations of sulfate, fine particle mass (PM(2.5)) and
      elemental carbon (EC) by season and subject for 25 individuals living in the
      Boston, MA, USA area. Ambient sulfate concentrations accounted for approximately
      70 to 80% of the variability in personal and indoor sulfate levels. Correlations
      between ambient and personal sulfate, however, varied by subject (0.1-1.0), with
      associations between personal and outdoor sulfate concentrations generally
      mirroring personal-ambient associations (median subject-specific correlations of
      0.8 to 0.9). Ambient sulfate concentrations are good indicators of personal
      exposures for individuals living in the Boston area, even though their levels may
      differ from actual personal exposures. The strong associations for sulfate
      indicate that ambient concentrations and housing characteristics are the driving
      factors determining personal sulfate exposures. Ambient PM(2.5) and EC
      concentrations were more weakly associated with corresponding personal and indoor
      levels, as compared to sulfate. For EC and PM(2.5), local traffic, indoor sources
      and/or personal activities can significantly weaken associations with ambient
      concentrations. Infiltration was shown to impact the ability of ambient
      concentrations to reflect exposures with higher exposures to particles from
      ambient sources during summer. In contrast in the winter, lower infiltration can
      result in a greater contribution of indoor sources to PM(2.5) and EC exposures.
      Placing EC monitors closer to participants' homes may reduce exposure error in
      epidemiological studies of traffic-related particles, but this reduction in
      exposure error may be greater in winter than summer. It should be noted that
      approximately 20% of the EC data were below the field limit of detection, making
      it difficult to determine if the weaker associations with the central site for EC
      were merely a result of methodological limitations.

PMID- 18728901
TI  - Seasonal variation of polycyclic aromatic hydrocarbons in soil and air of Dalian
      areas, China: an assessment of soil-air exchange.
AB  - The seasonal variations of concentrations of PAHs in the soil and the air were
      measured in urban and rural region of Dalian, China in 2007. In soil, mean
      concentrations of all PAHs in summer were larger than those in winter, whereas
      the concentrations of heavier weight PAHs in winter were larger than those in
      summer. Winter/summer concentration ratios for individual PAHs (R(W/S)) increased
      with the increase of molecular weight of PAHs in soil, indicating that PAHs with
      high molecular weight were more easily deposited to soil in winter than summer.
      In air, mean concentrations of all PAHs in winter were larger than those in
      summer. In comparison with the R(W/S) in soil, all the values of R(W/S) in air
      were larger than one indicating that the entire individual PAH concentrations in
      winter were larger than those in summer. The average concentration composition
      for each PAH compound in soil and air samples was determined and the seasonal
      change of PAH profile was very small. It was suggested that PAHs in soils and air
      had the same or similar sources both in winter and summer. The approach to the
      soil-air equilibrium was assessed by calculating fugacity quotients between soil
      and air using the soil and air concentrations. The calculated soil-air fugacity
      quotients indicated that soil acted as a secondary source to the atmosphere for
      all lighter weight PAHs (two-three rings) and it will continue to be a sink for
      heavier weight PAHs (five-six rings) in the Dalian environment, both in winter
      and summer. Medium weight PAHs (four-five rings) were close to the soil-air
      equilibrium and the tendency shifted between soil and air when season or function
      region changed. The fugacity quotients of PAHs in summer (mean temperature 298 K)
      were larger than those in winter (mean temperature 273 K), indicating a higher
      tendency in summer than winter for PAHs to move from soil to air. The variation
      of ambient conditions such as temperature, rainfall, etc. can influence the
      movement of PAHs between soil and air. Most of the fugacity quotients of PAHs for
      the urban sites were larger than that for the rural site both in winter and
      summer. This phenomenon may be related with that the temperatures in urban sites
      were higher than those in the rural site because of the urban heat island effect.

PMID- 18728900
TI  - Distribution of antifouling biocides in California marinas.
AB  - Antifouling biocides are used to prevent the settlement and growth of organisms
      on submerged surfaces. Irgarol 1051 is currently among the most widely used
      organic booster biocides worldwide. This study reports Irgarol 1051, its major
      metabolite M1 (aka GS26575), and diuron concentrations found in selected
      California marinas. Seasonal water samples (n = 46) were collected during the
      summer and fall of 2006 from eleven marinas throughout Southern and Northern
      California. The samples were extracted using solid phase extraction and analysed
      utilizing liquid chromatography tandem mass spectrometry (LC-MS-MS) with
      electrospray ionization. All three compounds were detected in all samples,
      representing a 100% frequency of occurrence and indicating widespread use around
      the sampled marinas. Irgarol concentrations ranged from 12 to 712 ng L(-1)
      (average 102 ng L(-1)), M1 concentrations were 1-217 ng L(-1) (average 31 ng L(
      1)), and diuron concentrations were 5-27 ng L(-1) (average 13 ng L(-1)). In
      general, concentrations of both Irgarol (15-712 ng L(-1)) and M1 (1-217 ng L(-1))
      were greater in samples collected during the summer, corresponding to the peak of
      the boating season. The detected diuron concentrations in most cases were greater
      for fall samples (7-27 ng L(-1)), and probably represented a combination of non
      agricultural (rights of way) and agricultural applications of diuron in
      California. The maximum Irgarol concentration detected in California marinas in
      summer 2006 (712 ng L(-1)) was five times greater than the Irgarol concentration
      suggested as the plant toxicity benchmark (136 ng L(-1)). Twenty three percent of
      samples from California marinas in this study exceeded this benchmark, suggesting
      that detected Irgarol concentrations may be high enough to cause changes in
      phytoplankton communities in the sampled marinas.

PMID- 18728905
TI  - Moose Consort Strobe and Miame Stard Remark or how can we improve the quality of
      reporting studies.

PMID- 18728906
TI  - Systematic review of interventions for reducing occupational stress in health
      care workers.
AB  - OBJECTIVES: This study evaluated the effectiveness of interventions in reducing
      stress at work among health care workers. METHODS: A systematic search was
      conducted of the literature on reducing stress or burnout in health care workers.
      The quality of the studies found was then appraised and the results combined. A
      meta-analysis was performed when appropriate. RESULTS: Altogether 14 randomized
      controlled trials, three cluster-randomized trials, and two crossover trials,
      comprising 2812 participants, were included. Only two trials were of high
      quality. The following comparisons were possible: person-directed interventions
      versus no intervention, person-work interface interventions versus no
      intervention, and organizational interventions versus no intervention. Person
      directed interventions can reduce stress [standardized mean difference (SMD) 
      0.85, 95% confidence interval (95% CI) -1.21 - -0.49] and burnout, measured as
      emotional exhaustion [weighted mean difference (WMD) -5.82, 95% CI -11.02 - 
      0.63) and lack of personal accomplishment (WMD -3.61; 95% CI -4.65 - -2.58). They
      also reduce anxiety, measured as state anxiety (WMD -9.42, 95% CI -16.92 - -1.93)
      and trait anxiety (WMD -6.91, 95% CI -12.80 - -1.01). Person-work interface
      interventions can reduce burnout, measured as depersonalization [mean difference
      (MD) -1.14, 95% CI -2.18 - -0.10]. Organizational interventions can also reduce
      stress symptoms (MD -0.34; 95% CI -0.62 - -0.06) and general symptoms (MD -2.90,
      95% CI -5.16 - -0.64). No harmful effects were reported. CONCLUSIONS: Limited
      evidence is available for a small, but probably relevant reduction in stress
      levels from person-directed, person-work interface, and organizational
      interventions among health care workers. This finding should lead to a more
      active stress management policy in health care institutions. Before large-scale
      implementation can be advised, larger and better quality trials are needed.

PMID- 18728893
TI  - Quality control and quality assurance for particle size distribution measurements
      at an urban monitoring station in Augsburg, Germany.
AB  - Long-term observations of atmospheric constituents such as aerosol particles are
      increasingly needed to assess their impact on climate and human health. In
      contrast to particle mass concentration (MC), there are currently no standardized
      quality control (QC) and quality assurance (QA) procedures for the measurement of
      particle size distribution (PSD). This study describes some fundamental QC and QA
      procedures associated with the collection and evaluation of a 2 year dataset
      between 2005 and 2006 at an urban background monitoring site in Augsburg,
      Germany. The considered parametres include ambient PSD between 3 nm and 10 microm
      (merged from a twin differential mobility and an aerodynamic particle sizer,
      TDMPS and APS, respectively) as well as total particle number (TNC), length (LC)
      and MC determined by independent instruments. The hourly 1st and 0th moment of
      PSD showed good correlations with the independently measured LC (R(2) = 0.86) and
      TNC (R(2) = 0.79), respectively, the deviation for LC with 4% and for TNC with
      22% being rather small. The volume concentration (3rd moment) of hourly measured
      PSD and the resultant MC (when assuming a realistic apparent density of 1.5 g cm(
      3)) correlated well with the independently measured MC of PM(2.5) or PM(10) (R(2)
      > 0.86) and showed only small deviation from PM(2.5) (1%) or PM(10) (5%),
      respectively. The study demonstrates that the described QC and QA measures define
      both a high accuracy of the PSD measurements and their long-term comparability
      against data obtained in similar measurement programmes.

PMID- 18728909
TI  - Effects of shift rotation and the flexibility of a shift system on daytime
      alertness and cardiovascular risk factors.
AB  - OBJECTIVES: A controlled intervention study was conducted to evaluate the effects
      of two changes in shift characteristics on alertness and cardiovascular risk
      factors: a change in shift rotation (direction and speed) and a change in the
      flexibility of the shift system. METHODS: Altogether 84 male workers currently
      working in a backward-rotating shift system volunteered for the study. A total of
      40 men changed to a rapidly forward-rotating shift system, 22 changed to a more
      flexible shift system, and 22 remained with the old shift system. Health effects
      were studied with the use of clinical measurements, blood tests, and
      questionnaires before and after the shift changes. Analyses of variance were used
      with repeated measures to study associations of cardiovascular risk factors and
      daytime sleepiness according to the change in shift systems. RESULTS: The mean
      number of days on which the workers reported sleepiness decreased in the group
      with the forward-rotating shift system when compared with that of the group on
      the old shift system (from 2.9 to 2.1 days/week, P=0.02). Systolic blood pressure
      decreased (from 142 to 136 mm Hg, P=0.049), and heart rate showed a declining
      trend (from 66 to 60 beats/minute, P=0.06) in the flexible shift system when the
      three groups were compared. CONCLUSIONS: The study indicates that a faster speed,
      together with a change to the forward direction, in shift rotation alleviates
      daytime sleepiness. Combining individual flexibility with company-based
      flexibility in a shift system may have favorable effects on shift workers' blood
      pressure.

PMID- 18728908
TI  - Occupational physicians' perceived value of evidence-based medicine intervention
      in enhancing their professional performance.
AB  - OBJECTIVES: This study evaluated how physicians in a nonclinical setting perceive
      the value of an intervention with multifaceted evidence-based medicine with
      regard to enhancing their professional performance. METHODS: A qualitative study
      was conducted using focus groups and face-to-face interviews with 14 of the 48
      Dutch occupational physicians who participated in the intervention. The
      intervention combined a didactic course in evidence-based medicine with recurrent
      case-method learning sessions. During the sessions, the participants were
      challenged to discuss their cases and to give one another feedback on how to find
      information on cases. RESULTS: Five main themes and four subthemes were
      identified: professional behavior and quality of care (subtheme: transparency):
      occupational physicians associated being up-to-date with quality of care, and
      evidence-based medicine was associated with improvements in professional
      standards; critical attitude and improved recommendations: occupational
      physicians asked themselves more-profound questions and searched more for
      information; sharing knowledge: the peer-group sessions facilitated the sharing
      of knowledge; communication (subthemes: colleagues, clients and other
      specialists): the more soundly based recommendations enhanced self-confidence
      positively and therefore altered interaction with medical specialists in
      particular; and satisfaction and barriers: the occupational physicians were
      especially content with the structured discussion in the peer-group sessions.
      However, the intervention was very time consuming. CONCLUSIONS: The participants
      regarded the intervention as a useful method for enhancing their professional
      performance. They stated that they became more up-to-date and more self-confident
      by searching for and sharing knowledge. These actions resulted in more
      scientifically based recommendations and improved interaction with clients and
      other specialists. However, time constraints remain an important barrier.

PMID- 18728910
TI  - Cardiovascular risk factors and primary selection into shift work.
AB  - OBJECTIVES: This study examined differences between future shift workers and
      future day workers as regards cardiovascular risk factors before they began
      different work schedules and the differences that remained after control for
      sociodemographic factors and general self-efficacy. METHODS: Altogether 2870
      newly educated social and health care workers filled out a questionnaire a few
      weeks before finishing their formal training and again 1 year after graduation.
      They answered questions on diabetes, hypertension, lifestyle habits,
      sociodemographic factors, and general self-efficacy. RESULTS: In the unadjusted
      analyses, baseline obesity was associated with fixed evening work at follow-up.
      Minimal or light-to-moderate leisure-time physical activity was associated with a
      decrease in the odds ratio (OR) for two or three shifts including night work.
      Smoking status was associated with fixed evening work, fixed night work, and two-
      or three- shift work including night work. After adjustment for sociodemographic
      factors and general self-efficacy, smoking was prospectively associated with
      fixed evening work [OR 1.56, 95% confidence interval (95% CI) 1.21-2.02] and
      fixed night work (OR 1.64, 95% CI 1.04-2.56). Being an ex-smoker was associated
      with two- or three-shift work including night work (OR 1.85, 95% CI 1.28-2.68).
      The association between two- and three-shift work and smoking was only of
      borderline significance (OR 1.37, 95% CI 1.00-1.87). CONCLUSIONS: Compared with
      future day workers, fixed evening or fixed night workers already smoked more
      before they began shift work. Being an ex-smoker was significantly associated
      with two- or three-shift work including night work. These results indicate that
      smoking status should not solely be treated as a mediator between some variants
      of shiftwork schedules and cardiovascular diseases but should also be considered
      a confounder.

PMID- 18728907
TI  - Health-related effects of worksite interventions involving physical exercise and
      reduced workhours.
AB  - OBJECTIVES: This study examined the health-related effects of two worksite
      interventions, physical exercise and reduced workhours, on women employed in
      dentistry. METHODS: Six workplaces were randomized to one of the following three
      conditions: (i) 2.5 hours of weekly, mandatory physical exercise of middle-to
      high intensity to be performed during workhours (N=62), (ii) a reduction of full
      time weekly workhours from 40 to 37.5 hours (N=50), and (iii) reference. In all,
      177 women participated. Biomarkers and self-ratings in questionnaires were
      obtained before the intervention (T (1)), and six (T (2)) and 12 months (T (3))
      after the intervention. RESULTS: The results showed increased levels of physical
      activity and exercise in all of the groups, the level of physical exercise being
      significantly greater in the physical exercise group. Repeated-measures analyses
      of variance using data from T (1)and T (3)for biological measures and all three
      time points for self-ratings produced significant interaction effects for
      glucose, waist-to-hip ratio, and work ability and clear trends for general
      symptoms and upper-extremity disorders. Posthoc analyses showed that the results
      of the health-related measures differed between the interventions, decreased
      glucose and upper-extremity disorders in the exercise group, and increased high
      density lipoprotein and waist-to-hip ratio among those working reduced hours.
      CONCLUSIONS: These results show that the two interventions had small and varied
      effects on biomarkers and self-reports of different aspects of health among
      women. It is suggested that interventions involving a modest reduction in
      workhours seem to be more effective if these hours are used for physical
      exercise.

PMID- 18728911
TI  - A diary study to open up the black box of overtime work among university faculty
      members.
AB  - OBJECTIVES: This study aimed at opening up the black box of overtime work among
      university faculty members by providing information on (i) when faculty members
      work overtime, (ii) what activities are undertaken during overtime, and (iii) how
      overtime is experienced. METHODS: Data were collected among 120 Dutch faculty
      members who completed a general questionnaire (addressing general overtime hours,
      work characteristics, and well-being) and a 9-day diary study (with information
      on daily overtime hours, activities, and experiences). Analyses of variance were
      used to analyze the data. RESULTS: Overtime was very prevalent among faculty
      members, high overtime workers being nonfatigued, engaged employees with positive
      work characteristics. Overtime was unevenly distributed over the week, being
      common on Sunday and Monday and uncommon on Friday and Saturday. Overtime
      activities during the weekend differed from those during the workweek, relatively
      much time being spent on research during weekend overtime. Overtime activities
      were experienced differently than activities during regular hours, overtime work
      being experienced as less effortful and less stressful than regular workhours and
      weekend overtime being less pleasurable than regular hours and evening overtime.
      CONCLUSIONS: This detailed day-to-day mapping and evaluation of overtime work
      contributes to a better understanding of overtime work by demonstrating
      meaningful patterns of overtime over the (work)week and meaningful associations
      between overtime activities and time-contingent experiences. It is suggested that
      worktime control plays an important role in explaining the results.

PMID- 18728913
TI  - Follow-up study of cancer incidence after chlorophenol exposure in a community in
      southern Finland.
AB  - OBJECTIVES: In the 1970s and 1980s, people in a village in southern Finland had
      been exposed to high concentrations of chlorophenols in the drinking water and in
      fish from a nearby lake. An ecological analysis and a case-control study
      conducted around 1990 indicated significant excess in the incidence of non
      Hodgkin's lymphoma and soft-tissue cancer in the municipality and a relationship
      between the chlorophenol exposure and the incidence of these cancers. The present
      article reports a follow-up of cancer risk in the same study area during a 20
      year period after the closing of the old water intake plant, which was
      contaminated by chlorophenols. METHODS: The observed and expected numbers of
      cancer were obtained for three periods, 1953-1971 (before exposure), 1972-1986
      (during exposure) and 1987-2006 (after exposure), for all cancers combined and
      separately for cancers potentially related to chlorophenols. RESULTS: The present
      study demonstrates that all of the cancer risks returned to the average
      population level during the 20-year period after the old water intake plant was
      closed and chlorophenol exposure stopped. CONCLUSIONS: The rapid changes in
      cancer risk after changes in chlorophenol exposure suggest that chlorophenols may
      have a promotion effect in the carcinogenic process.

PMID- 18728912
TI  - Prediction of dropout from respiratory symptoms and airflow limitation in a
      longitudinal respiratory study.
AB  - OBJECTIVES: This study investigated the possibility that employees reporting
      respiratory symptoms were more likely than asymptomatic workers to dropout of a
      respiratory study carried out in Norwegian smelters. METHODS: The study included
      3924 employees in 24 Norwegian smelters. They were examined annually using a
      respiratory questionnaire and spirometry. The employees who did not meet for the
      follow-up within 18 months prior to the end of the study were considered
      dropouts. The data were analyzed using Cox regression for time-dependent
      covariates. RESULTS: The total and the median follow-up times were 16 997 and 4.9
      years, respectively. The overall dropout rate was 44.5 [95% confidence interval
      (95% CI) 41.5-47.8 per 1000 person-years]. The hazard ratio (HR) for dropout was
      1.38 (95% CI 1.15-1.66) for the workers reporting any respiratory symptom
      compared with the asymptomatic workers. The effect was the strongest among the
      employees who reported dyspnea, and it was stronger regarding symptoms at the
      last visit than for the baseline symptoms. Similarly, the hazard ratio for
      dropout for those with an airflow limitation [forced expiratory volume/forced
      vital capacity below the 5th percentile of the predicted value] was 1.31 (95% CI
      1.01-1.69) when they were compared with employees without any airflow limitation.
      CONCLUSIONS: Respiratory symptoms and airflow limitation are important predictors
      of dropout from a longitudinal respiratory study.

PMID- 18728915
TI  - Clinical application of virtual endoscopy as a support system for endoscopic
      sinus surgery.
AB  - CONCLUSIONS: Computer processing of conventional CT images can provide virtual
      endoscopic images (VEIs). Surgeons observing these images feel as if they are
      observing the lesion using an endoscope. Simulation based on animated VEIs before
      endoscopic sinus surgery (ESS) is useful for the improvement of surgical safety
      and surgeons' education. Although the production of VEIs requires certain
      surgical experience, after the production of VEIs, surgeons can repeat simulation
      of a surgical procedure and have confidence in the actual operation. OBJECTIVE:
      We investigated the clinical application of CT-reconstructed VEIs as a support
      system for ESS. MATERIALS AND METHODS: A GE Light Speed Ultra 16 as a 16-slice CT
      scanner and Advantage Workstation 4.2 were used. Software called Navigator in
      this workstation allows the production of CT-reconstructed VEIs. We applied
      simulation based on VEIs to endoscopic operations for mucocele or sinusitis.
      RESULTS: In nine cases of mucoceles and sinusitis, simulation based on animated
      VEIs was applied. According to the simulation, surgeries were performed, and the
      mucoceles and obstructed sinuses could be opened readily and safely. This system
      was more effective when there were landmarks such as polyps or irregular mucosal
      surfaces allowing macroscopic confirmation ahead of the viewpoint.

PMID- 18728926
TI  - Commentary on: "On the need for a specialist service within the generic hospital
      setting" by Robyn A. Wallace and Helen Beange (2008).

PMID- 18728925
TI  - On the need for a specialist service within the generic hospital setting for the
      adult patient with intellectual disability and physical health problems.

PMID- 18728918
TI  - Effect of baclofen on neuronal activity in the medial vestibular nucleus after
      unilateral surgical labyrinthectomy in rats.
AB  - CONCLUSIONS: Ipsilateral and contralateral medial vestibular nuclei (MVN) neurons
      respond differently to systemic injection of baclofen (4-amino-3-(4-chlorophenyl)
      butanoic acid), illustrating the plastic changes of the type B gamma-aminobutyric
      acid (GABA(B)) receptor during vestibular compensation. OBJECTIVES: To
      investigate the responsiveness of MVN neurons to baclofen during the early,
      partially compensated period after unilateral surgical labyrinthectomy. MATERIALS
      AND METHODS: MVN were localized using field potentials evoked by electrical
      stimulation, along with a stereotaxic atlas of rat brain. Neuronal activity in
      MVN was recorded and analyzed in rats that had undergone labyrinthectomy with and
      without administration of baclofen. RESULTS: After left labyrinthectomy the mean
      discharge rate in ipsilesional MVN decreased, but it was nearly restored by
      postoperative day 8. Baclofen (3 mg/kg) reversed the mean discharge rates between
      bilateral MVN at days 4 and 8 after surgical labyrinthectomy. In addition, the
      reduction ratio of the right MVN neurons was higher than that of the left MVN
      neurons.

PMID- 18728919
TI  - Dual-frequency ultrasound technique minimizes errors induced by soft tissue in
      ultrasound bone densitometry.
AB  - BACKGROUND: Most bone ultrasound devices are designed for through-transmission
      measurements of the calcaneus. In principle, ultrasound backscattering
      measurements are possible at more typical fracture sites of the central skeleton.
      Unfortunately, soft tissue overlying the bones diminishes reliability of these
      measurements. PURPOSE: To apply the single-transducer dual-frequency ultrasound
      (DFUS) technique to eliminate the errors induced by soft tissue on the
      measurements of integrated reflection coefficient (IRC) in human distal femur in
      vivo. MATERIAL AND METHODS: Ultrasound and dual-energy X-ray absorptiometry (DXA)
      examinations were conducted on a bodybuilder during a 21-week training and
      dieting period. RESULTS: Significant changes in quantity and composition of soft
      tissue took place during the diet. However, DXA measurements showed no
      significant effects on bone density measurements. The single transducer DFUS
      technique enabled the determination of local soft-tissue composition, as verified
      by comparison with the DXA (r=0.91, n=8, p<0.01). Further, the technique
      eliminated the soft-tissue-induced error from IRC measured for the bone. The
      uncorrected IRC associated significantly with the change in local soft-tissue
      composition (r=-0.83, n=8, p<0.05), whereas the corrected IRC values showed no
      significant dependence (r=-0.30, n=8, p=0.46) on local soft-tissue composition.
      CONCLUSION: The DFUS technique may significantly enhance the accuracy of clinical
      ultrasound measurements of bone.

PMID- 18728917
TI  - Efficacy of spinal needle aspiration for epiglottic abscess in 90 patients with
      acute epiglottitis.
AB  - CONCLUSION: Patients with epiglottic abscesses showed more severe symptoms than
      those with acute epiglottitis and were at increased risk of airway compromise.
      All 11 patients with epiglottic abscesses underwent spinal needle aspiration; all
      were cured without severe complications. These findings indicate that spinal
      needle aspiration is both safe and effective in patients with epiglottic
      abscesses. OBJECTIVES: Acute epiglottitis is a disease that may become serious or
      even fatal because of sudden upper airway obstruction. An epiglottic abscess may
      result from a coalescent epiglottic infection due to acute epiglottitis or
      secondary infection of an epiglottic mucocele. There have been few reports
      comparing acute epiglottitis with epiglottic abscess. We therefore assessed the
      clinical characteristics of each condition, as well as the efficacy of spinal
      needle aspiration and drainage of epiglottic abscesses. PATIENTS AND METHODS: We
      retrospectively reviewed the records of 90 hospitalized patients diagnosed with
      acute epiglottitis and epiglottic abscess by flexible nasopharyngolaryngoscopy
      between March 2006 and February 2008. All patients were treated with medication;
      in addition, those with epiglottic abscess underwent spinal needle aspiration.
      RESULTS: Of 90 patients, 79 had acute epiglottitis and 11 had epiglottic
      abscesses. Acute epiglottitis was most common in May (16.5%) and epiglottic
      abscesses were most common in June (27.3%). The most common symptoms were sore
      throat (91.1%), dysphagia (38.9%), voice change (33.3%), and dyspnea (16.7%). All
      patients were treated with antibiotics and steroids. The mean length of
      hospitalization was 5 days. No patient required a tracheostomy or orotracheal
      intubation.

PMID- 18728929
TI  - Evaluation of the profile of the immune cell infiltrate in lichen planus, discoid
      lupus erythematosus, and chronic dermatitis.
AB  - AIMS: The term 'interface dermatitis' refers to those dermatoses in which an
      inflammatory process involves the dermoepidermal junction, with injury and even
      necrosis of the basal cell keratinocytes. Interface dermatitis can be
      characterised further as being either vacuolar or lichenoid changes. Immune cell
      infiltrate is a constant feature in interface dermatitis. In this study, we
      hypothesised that 'the profile of the immune cell infiltrate varies between
      lichenoid and vacuolar interface dermatitis'. This investigation tries to test
      this hypothesis and to characterise immune cells in interface dermatitis.
      METHODS: Thirty-one interface dermatitis lesions (interface dermatitis group: 19
      cases of lichen planus, LP; and 12 cases of discoid lupus erythematosus, DLE) and
      20 specimens of normal skin (control group) were examined using immunoperoxidase
      staining methods. Antibodies targeting histiocytes/dendritic cells (CD68+), T
      cells (CD3+), B cells (CD20+), T cells with either cytotoxic potential (TIA-1+)
      or cytotoxic activity (Granzyme-B+) were used to decorate the immune cells. In
      addition, 16 cases of chronic dermatitis [lichen simplex chronicus (LSC), non
      interface dermatitis group] were included to substantiate findings in the
      interface dermatitis group. The results were scored as mean values of positively
      stained immune cells. RESULTS: The numbers of immune cells were significantly
      high (p < 0.05) in the lesional skin (LP, DLE and LSC) compared with normal skin.
      The most prevalent cell populations were CD3+ T lymphocytes followed by CD68+
      cells. Most of the CD3+ cells were resting (TIA-1+, cytotoxic potential) rather
      than active T cells (Granzyme-B+, active cytotoxicity). Numeric variations were
      seen between interface and chronic dermatitis groups with significant increase of
      the density of immune cells in the interface dermatitis (p < 0.05). We found some
      variations in the composition and distribution of immune cell infiltrate between
      LP (lichenoid change) and DLE (vacuolar changes). The mean counts of CD3+ cells
      were high in LP compared with DLE (p < 0.05). Alternatively, the density of CD20+
      cells was high in DLE compared with LP (p < 0.05). High density of CD3+
      (perivascular location and dermoepidermal junction, p < 0.05) positively stained
      cells was found in LP compared with DLE. In contrast, high density of CD20+
      (perivascular location and dermoepidermal junction, p < 0.05), TIA-1+ and
      Granzyme-B+ (perivascular location and dermoepidermal junction, p > 0.05)
      positively stained cells was observed in DLE compared with LP. CONCLUSIONS: Here
      we report some variations in the profile (density and positioning) of the immune
      cell infiltrate between LP and DLE. These variations include high density of
      CD68+ cells and CD3+ T lymphocytes in LP and DLE; and the numeric dominance of
      CD20+ B-lymphocytes in DLE compared with LP. Also, some differences in the
      density of TIA-1+ and Granzyme-B+ cytotoxic T cells between LP and DLE were
      observed. Our findings suggest a possible link between the type of these cells
      and the development of interface dermatitis lesions. The possible ramifications
      of these findings are open for further investigations.

PMID- 18728927
TI  - Invited commentary on Wallace and Beange (2008): "On the need for a specialist
      service within the generic hospital setting".

PMID- 18728920
TI  - Childhood predictors of the metabolic syndrome in adulthood. The Cardiovascular
      Risk in Young Finns Study.
AB  - BACKGROUND: Obese youths may be susceptible to develop the metabolic syndrome
      (MS) later in life. AIM: To study childhood predictors of MS in adulthood.
      METHOD: Prospective cohort study including 2,195 subjects, aged 3-18 years at
      base-line in 1980, who were re-examined in 1983, 1986, and 2001. RESULTS: In
      adults (aged 24-39 years) in 2001, the prevalence of MS (using the International
      Diabetes Federation criteria) was 19% in men and 12% in women. Multivariable
      logistic regression model selected obesity, male sex, high triglycerides, high
      insulin, high C-reactive protein (CRP), and family history of hypertension and
      type 2 diabetes, as independent predictors of adult MS. Youth obesity (body mass
      index (BMI)>80th age- and sex-specific percentile) was the strongest risk factor
      for MS. During the 21-year follow-up, there was an increasing trend in BMI,
      insulin, systolic blood pressure, and triglycerides, and a decreasing trend in
      high-density lipoprotein cholesterol in obese subjects who developed MS in
      adulthood compared to those obese subjects who did not develop MS. CONCLUSIONS:
      Youth determinants of adult MS included obesity, high triglycerides, high
      insulin, high CRP, and family history of hypertension and type 2 diabetes.
      Identifying these risk factors at an early stage could help identifying children
      and adolescence at greater risk of developing MS later in life.

PMID- 18728928
TI  - Interviews with children of persons with a severe mental illness: investigating
      their everyday situation.
AB  - Research on children of persons with a severe mental illness focuses
      predominantly on parents' and others' perceptions. Children of mentally ill
      parents form a vulnerable group that has not been adequately paid attention to in
      psychiatric care institutions. Comparatively little is known about the children's
      recognition of their parents and the everyday situation of these families. The
      aim of the study was to investigate experiences of their life situation in
      children 10-18 years of age in a family with a parent with a severe mental
      illness. Eight children were interviewed concerning their everyday life
      situation. The interviews were analysed inspired from using thematic analysis.
      From the analysis of the material emerged aspects concerning the following
      themes: need for conversation, love for their family, maturity, experience of
      fear and blame, feelings of loneliness, responsibility and associated stigma.
      This study highlights the situation experienced by children of severely mentally
      ill persons who also are parents. The study may be found to be a basis for
      inspiring structured interventions and treatments programmes including children
      of the adult patients seeking psychiatric treatment.

PMID- 18728921
TI  - Management of haemorrhagic bullous lesions in Henoch-Schonlein purpura: is there
      any consensus?
AB  - Henoch-Schonlein purpura (HSP) is the most common form of vasculitis affecting
      children. The cutaneous manifestations classically present as urticarial wheals,
      erythematous maculopapules, petechiae, purpura or oedema, which
      characteristically involve the lower extremities and buttocks. Haemorrhagic
      bullous lesions are a recognized but rare occurrence with HSP in children. We
      report a 6-year-old boy with HSP who developed extensive haemorrhagic bullae
      requiring dermatological referral and treatment. Scrutiny of our management and
      available literature reveals a lack of consensus in the management of extensive
      cutaneous involvement in HSP.

PMID- 18728916
TI  - In vivo measurement of O(2) and CO(2) gas exchange across the human tympanic
      membrane.
AB  - CONCLUSION: The hypothesis that the human tympanic membrane (TM) is permeable to
      CO(2) and O(2) at physiologic pressure gradients is supported but additional
      experiments need to be done to validate this methodology. OBJECTIVE: Gas exchange
      between the middle ear and adjacent compartments determines the trajectory of
      middle ear pressure change. Little information is available regarding the
      permeability of the TM to physiological gases. This study aimed to determine in
      vivo if the human TM is permeable to O(2) and CO(2) at physiologic transTM
      pressure gradients. SUBJECTS AND METHODS: An ear canal (EC) probe (ECP)
      constructed from a custom-fitted acrylic body, a glass capillary tube enclosing
      an oil meniscus to maintain ambient ECP + EC pressure and a silica glass
      microtube linked to a mass spectrometer (MS) for measuring gas composition was
      hermetically sealed within one EC in each of 15 adults. ECP + EC volume was
      measured and gas samples were taken at 10 min intervals for 1 h. Epinephrine
      (1:100 000) was applied topically to the ipsilateral TM to decrease blood flow
      and the experiment was repeated. The ECP + EC pressures of O(2) (32 AMU) and
      CO(2) (44 AMU) were regressed on time and the slope divided by the predicted
      transTM partial-pressure gradients to yield estimates of transTM O(2) and CO(2)
      conductance. RESULTS: Consistent with expectations for transTM gas exchange, ECP
      + EC O(2) decreased and CO(2) increased during the experiments. CO(2) increase
      was faster after application of epinephrine to the TM. The ratio of O(2)/CO(2)
      conductances was not consistent with the gas exchange through a primarily water
      or lipid diffusion barrier.

PMID- 18728914
TI  - Detection of pregnancies with high risk of fetal macrosomia among women with
      gestational diabetes mellitus.
AB  - OBJECTIVE: To compare the frequency of fetal macrosomia and Erb's palsy in two
      groups of women with gestational diabetes mellitus (GDM) and in healthy controls.
      DESIGN: Retrospective clinical study of women with GDM. SETTING: Pregnant women
      in Greater Helsinki area. POPULATION: Nine hundred and five pregnancies and
      newborn infants of women with GDM and 805 non-diabetic controls. METHODS: GDM was
      diagnosed by a 2-hour oral glucose tolerance test (OGTT) among women with risk
      factors for GDM. The treatment of GDM was resolved by a 24-hour glucose profile
      obtained after 2 or 3 abnormal glucose values in the OGTT. Patients with a
      history of insulin-treated GDM in a previous pregnancy and those with a fasting
      glucose over 6 mmol/l underwent a 24-h glucose profile directly without a
      preceding OGTT. MAIN OUTCOME MEASURES: Fetal macrosomia, defined as a birth
      weight (adjusted for sex and gestational age) of >2.0 SD above the mean of a
      Finnish standard population. Erb's palsy. RESULTS: 385 women (42.5%) were treated
      with insulin and diet and 520 (57.5%) with diet only. Macrosomia occurred more
      often in the insulin-treated group (18.2%, p<0.001) compared with the diet
      treated group (4.4%) and the controls (2.2%). The rate of Erb's palsy was 2.7% in
      the insulin-treated group, 2.4% in the diet-treated group, compared with 0.3% in
      the controls (p<0.001). CONCLUSION: The 24-hour glucose profile performed after
      the diagnosis of GDM clearly distinguishes between low-risk (diet-treated) and
      high-risk (insulin-treated) for fetal macrosomia in GDM pregnancies.

PMID- 18728932
TI  - Cystatin C as a filtration marker--haemodialysis patients expose its strengths
      and limitations.
AB  - OBJECTIVE: The reliability of serum cystatin C (s-Cys) as a filtration marker
      depends on the intra- and inter-individual variation and influence of non-renal
      factors of its production rate (Cys(pr)), non-renal clearance (CL(nr)) and
      sieving coefficient (S). Haemodialysis patients with no residual renal function
      would be the best population in which to investigate these variables, which
      otherwise require reliable GFR measurements. MATERIAL AND METHODS: Seventy-nine
      haemodialysis (HD) patients with negligible residual renal function (Group 1)
      were investigated and compared with 55 HD patients with varying degrees of
      residual renal function (Group 2) and 923 non-dialysis patients (Group 3). The
      equation eGFR = Cys(pr)/s-Cys-CL(nr) was used to analyse the turnover and
      variation of cystatin C. RESULTS: A formula for estimating GFR, eGFR = 99/s-Cys
      14.1, calculated from Group 3, was shown to fit the HD patients. The measured s
      Cys in Group 1 was 6.9+/-0.9 and 6.4+/-1.1 mg/L in Group 2. The calculated 95%
      confidence interval of eGFR of +/-(30-40) % increased sharply below GFR 20
      mL/min/1.73 m(2), which means that s-Cys cannot be used for calculating low GFR,
      including the residual GFR of dialysis patients. CONCLUSIONS: Nicotine users in
      Group 1 had significantly higher s-Cys than non-users (7.5+/-0.9 mg/L compared to
      6.7+/-0.8; p = 0.0008), which may be a factor to include in the eGFR formulae.
      However, s-Cys was independent of non-renal factors such as sex, age, LBM, body
      weight, malnutrition and CRP and also of changes in CRP.

PMID- 18728922
TI  - The cost-effectiveness of rosacea treatments.
AB  - BACKGROUND: Topical and oral antibiotic/anti-inflammatory agents are mainstays of
      therapy for rosacea. However, costs and efficacies of these therapies vary
      widely. OBJECTIVE: To determine relative cost-effectiveness of common therapeutic
      regimens using published data. METHODS: Average daily costs (ADC) were determined
      based on treatment frequency and estimated gram usage for facial application of
      topical regimens of metronidazole (0.75%, 1%), azelaic acid (15%, 20%), sodium
      sulfacetamide and sulfur 10%/5%, and oral regimens of tetracycline, doxycycline,
      and isotretinoin. The ADC was compared with published efficacy rates from
      clinical trials, with efforts to standardize outcome measures. Based on these
      efficacy rates, costs per success were calculated and combined with office visit
      costs to estimate the total cost for each treatment for a 15-week period.
      RESULTS: The medication cost per treatment success of topical regimens ranged
      from $60.90 ($205.40, total, including office visits) for metronidazole 1% gel
      once daily, to $152.25 ($296.75, total) for azelaic acid 20% cream twice daily.
      Tetracycline 250 mg/day was the least costly oral agent at $6.30 per treatment
      success, or $150.80 total. CONCLUSION: Based on our best assessments of
      retrospective data from the literature, metronidazole 1% gel, once daily, was
      considerably less costly than several other branded and generic alternatives.

PMID- 18728933
TI  - Effects of dihydralazine on renal water and aquaporin-2 excretion in humans.
AB  - OBJECTIVE: Dihydralazine is a vasodilator that lowers blood pressure, but often
      also leads to significant water and sodium retention. To characterize the effect
      of dihydralazine on renal sodium and water handling, we tested the hypothesis
      that dihydralazine causes water retention parallel with an increase in urinary
      excretion of aquaporin-2 (u-AQP2) in healthy humans. MATERIAL AND METHODS: The
      effect of intravenous infusion of dihydralazine in three doses (3.125 mg, 6.250
      mg and 9.375 mg) on urinary AQP2, water and sodium excretion, heart rate (HR),
      blood pressure (BP) and vasoactive hormones was measured in a randomized, placebo
      controlled, double-blind, crossover study in 17 healthy subjects. Glomerular
      filtration rate (GFR) and renal tubular function were determined with the
      continuous infusion clearance technique and vasoactive hormones with
      radioimmunoassays. RESULTS: Dihydralazine compared to placebo had no impact of u
      AQP2 (effect of dihydralazine versus placebo +/-SE) (-0.074+/-0.048 ng/min versus
      -0.015+/-0.034 ng/min; p = 0.42), despite significant reductions in urine output
      and free water clearance after 9.375 mg of dihydralazine. Dihydralazine
      significantly lowered BP and increased HR, plasma levels of angiotensin II and
      (except after 3.125 mg) atrial natriuretic peptide, while plasma levels of
      vasopressin, GFR and fractional excretions of sodium and lithium were not
      significantly changed. CONCLUSIONS: These findings suggest that dihydralazine
      increases water re-absorption in the distal tubules, independently of vasopressin
      and of sodium re-absorption. Furthermore, our study does not support an effect of
      the sympathetic nervous system, the renin-angiotensin system and the natriuretic
      peptide system on u-AQP2 regulation.

PMID- 18728923
TI  - Patient-reported outcomes from a multicenter, randomized, vehicle-controlled
      clinical study of MAS063DP (Atopiclair) in the management of mild-to-moderate
      atopic dermatitis in adults.
AB  - BACKGROUND: MAS063DP (Atopiclair) is a topical cream approved for symptomatic
      relief in the treatment of atopic and contact dermatitis. METHODS: This was a
      multicenter, randomized, double-blind, vehicle-controlled study in adults with
      mild-moderate atopic dermatitis. Patients were given MAS063DP or vehicle (2:1)
      three times per day to areas affected by atopic dermatitis for up to 50 days. A
      patient global assessment change from baseline was determined at days 8, 22, 36,
      and 50. Patient total body pruritus (visual analog scale) and patient opinion on
      treatment acceptability were also assessed. RESULTS: A total of 218 patients
      (active: n = 145, vehicle: n = 73) were enrolled. At Day 22, 77% of patients on
      MAS063DP had a patient global assessment of good improvement or better versus 21%
      on vehicle (p<0.0001, chi-squared test). Similarly, more patients had improvement
      in itch over their total body on MAS063DP than on vehicle (p<0.0001). CONCLUSION:
      MAS063DP treatment results in patient-perceived improvements in mild-moderate
      atopic dermatitis.

PMID- 18728936
TI  - The efficacy of rehabilitation for patients with rheumatoid arthritis: comparison
      between a 4-week rehabilitation programme in a warm and cold climate.
AB  - OBJECTIVES: To investigate the long-term effect (week 16) of a 4-week
      rehabilitation programme for patients with rheumatoid arthritis (RA) and to
      compare the effect of this intervention given in a Mediterranean or a Norwegian
      climate. METHODS: A randomized, controlled, parallel group design, where 124 RA
      patients applying for rehabilitation were randomized to a rehabilitation
      programme either in Norway or in a Mediterranean climate. The participants were
      examined clinically immediately before (week 0) and after (week 4) the
      rehabilitation period as well as in week 16 and answered a mailed questionnaire
      in week 28. The 28-Joint Disease Activity Score (DAS28), American College of
      Rheumatology (ACR) response and physical tests were used to measure clinical
      response. RESULTS: The baseline DAS28 value 4.45 (1.16) was reduced by -0.95
      (1.05) in the Mediterranean climate and the baseline DAS28 value 4.18 (1.17) was
      reduced by -0.37 (0.92) in the Norwegian climate at week 16 (p = 0.003). An ACR20
      improvement was achieved in 25% of the patients treated in the Mediterranean
      climate and in 15% of those treated in the Norwegian climate. Sustained
      improvement in all ACR core components at week 16 and in patient's assessment of
      health status at week 28 was found in the patients treated in the Mediterranean
      climate only. Tests of physical function, the 6-Minute Walk Test (6MWT) and the
      Timed Up and Go (TUG), showed comparable improvements in patients treated in both
      climates. CONCLUSIONS: RA patients showed immediate positive effects with regard
      to disease activity, physical function, and symptoms during a 4-week
      rehabilitation programme. The effects on disease activity and symptoms were
      larger and better maintained at least 3 months after rehabilitation in a warm
      rather than in a cold climate.

PMID- 18728939
TI  - Promoting mental health in later life.

PMID- 18728934
TI  - Type 2 diabetes and multidrug-resistant tuberculosis.
AB  - The association between tuberculosis (TB) and diabetes is re-emerging with the
      epidemic of type 2 diabetes (T2DM). We analyzed retrospective data from 2878 TB
      patients across the Texas/Mexico border. Overall, 161/2878 (5.6%) patients had
      MDR TB (resistance to rifampin and isoniazid): Texas 49/1442 (3.4%) and Mexico
      112/1436 (7.8%). In Texas, MDR TB was significantly associated with T2DM (OR 2.1,
      95% CI 1.1-4.2) when adjusted for age, gender, drug and alcohol abuse, HIV
      infection and history of previous episode of TB; and in Mexico (OR 1.80, 95% CI
      1.1-2.9) when adjusted for age and gender. Patients with T2DM in both countries
      were more likely to be compliant with DOTS therapy (Texas: OR 2.4, 95% CI 1.1
      5.4) than patients without T2DM. In Texas, all but 3 of the T2DM patients with
      MDR TB were resistant at their first culture at the time of diagnosis. It is
      possible that impaired immunity in T2DM increases susceptibility to infection
      with resistant strains.

PMID- 18728935
TI  - Diffuse periarterial involvement in systemic fibrosclerosis with Riedel's
      thyroiditis, sclerosing cholangitis, and retroperitoneal fibrosis.

PMID- 18728938
TI  - Genetic variants of organic cation transporter 2 (OCT2) significantly reduce
      metformin uptake in oocytes.
AB  - 1. The authors sought to evaluate the contribution of organic cation transporters
      (OCTs) to the renal tubular transport of metformin using LLC-PK1 cells as an in
      vitro model for the renal proximal tubule, and to investigate the effects of
      three non-synonymous genetic variants of OCT2 on the transport activity of
      metformin in vitro using an oocyte over-expression system. 2. The basolateral-to
      apical transport of metformin was significantly greater than the apical-to
      basolateral transport and showed concentration dependency with the kinetic
      parameters: maximum transport rate (V(max)), 922 pmol min(-1) per 5 x 10(5)
      cells; Michaelis-Menten constant (K(m)), 393 microM; intrinsic clearance
      (CL(int)), 2.35 microl min(-1) per 5 x 10(5) cells; and diffusion constant
      (K(d)), 0.33 microl min(-1) per 5 x 10(5) cells. The basolateral-to-apical
      transport of metformin was inhibited by phenoxybenzamine, an inhibitor of OCTs,
      but not by cyclosporine A, MK571, or fumitremorgin C, which are inhibitors of P
      glycoprotein, multidrug resistance proteins (MRPs), and breast cancer resistance
      protein (BCRP), respectively, suggesting that OCTs play a role in renal tubular
      secretion of metformin. 3. Metformin uptake was much greater in oocytes
      expressing OCT2-wild type (OCT2-WT) than OCT1-WT compared with uptake in water
      injected oocytes. Uptake was significantly decreased in oocytes expressing OCT2
      T199I, -T201M, and -A270S compared with that in OCT2-WT, suggesting that
      metformin is a better substrate for OCT2 than for OCT1 and that the amino acid
      substituted variants of OCT2 cause a functional decrease in metformin uptake. 4.
      In conclusion, the genetic variants of OCT2 (OCT2-T199I, -T201M, and -A270S)
      decreased the transport activity of metformin and thus may contribute to the
      inter-individual variation in metformin disposition as OCT2 plays a pivotal role
      in renal excretion, the major disposition route of metformin.

PMID- 18728940
TI  - Examination of a theoretical model of psychological resilience in older age.
AB  - OBJECTIVE: This article integrates a number of theoretical perspectives and
      examines the concept of psychological resilience in older age. Drawing on the
      literature it is hypothesised that an overarching construct-resilience-accounts
      for the functioning of a number of psychological resources (self-esteem, personal
      competence and control). METHOD: The factorial validity of the resources as
      indicators of resilience is tested using confirmatory factor analysis. The
      analyses focus on previously unexplored survey data drawn from a representative
      sample of people aged between 50 and 90 in England, Wales and Scotland (N=1847).
      RESULTS: The results find a common factor (a higher-order model) provides the
      best explanation of the relationships between the resources, demonstrating an
      important first account for developing further work on this concept. CONCLUSION:
      Exploring what might form the basis of resilience from a psychological
      perspective enables a deeper understanding of why some individuals can remain
      positive in difficult circumstances, particularly some of the challenges of
      ageing.

PMID- 18728941
TI  - Enhancing later life: how older people perceive active ageing?
AB  - OBJECTIVE: To identify older people's perceptions of active ageing, and to
      compare them with the literature, and with older people's perceptions of
      successful ageing and quality of life. DESIGN: Face-to-face interview survey with
      337 people aged 65+ living at home in Britain. RESULTS: The most common
      perceptions of active ageing were having/maintaining physical health and
      functioning (43%), leisure and social activities (34%), mental functioning and
      activity (18%) and social relationships and contacts (15%). A third rated
      themselves as ageing 'Very actively', and almost half as 'Fairly actively'.
      Independent predictors of positive self-rated active ageing were optimum health
      and quality of life. DISCUSSION: Main sub-themes of active ageing included
      exercising the body and mind in order to maintain health and functioning.
      People's views focussed on basic definitions such as social, physical and mental
      health and activity, probably reflecting the novelty of the concept to them,
      thereby excluding frail older people from active ageing. Comparisons with
      definitions of successful ageing and quality of life showed overlap, but the
      latter were portrayed as 'states of being'. This is consistent with models which
      propose quality of life as the end-point of active ageing.

PMID- 18728943
TI  - Social productivity and depressive symptoms in early old age-results from the
      GAZEL study.
AB  - OBJECTIVES: We test associations of frequency of performing three types of
      socially productive activities (voluntary work, informal help and caring for a
      person) with depressive symptoms in older people. Are depressive symptoms
      negatively associated with frequency in all three types or rather in those
      activities that are characterized by a high degree of autonomy and perceived
      control? METHODS: Data on social activities and frequency of performance were
      collected in the frame of the annual follow-up of the French GAZEL cohort study
      in 2005. Depressive symptoms were measured by the CES-D scale. Perceived control
      was assessed by two items of a quality of life measure (CASP-19). Total of 14477
      respondents aged 52-66 years completed a standardized questionnaire. Linear
      regression models were calculated adjusting for important confounders including
      self-rated health assessed during the previous year. RESULTS: In activities
      characterized by high autonomy (in particular voluntary work) a negative
      association of frequency with depressive symptoms was observed, whereas the
      reverse effect was found in the type of activity with low autonomy (care for a
      person). Perceived control mediated in part the association of frequency of
      activity with depressive symptoms. CONCLUSION: Being often socially productive in
      early old age may contribute to well-being to the extent that autonomy and
      perceived control are given.

PMID- 18728942
TI  - Addressing loneliness in later life.
AB  - OBJECTIVES: Social and solitary pastimes with the potential to ameliorate the
      experience of loneliness among older individuals were investigated for the
      purpose of informing future interventions designed to reduce the negative
      consequences of social isolation. METHOD: Nineteen individual interviews with
      Australians aged 65 years and older. RESULTS: Several pastimes were described by
      interviewees as instrumental in determining whether the increasing social
      isolation they experience in older age results in feelings of emotional isolation
      and thus of loneliness. CONCLUSION: The specific behaviours that were found to
      ameliorate loneliness included utilizing friends and family as an emotional
      resource, engaging in eating and drinking rituals as a means of maintaining
      social contacts, and spending time constructively by reading and gardening.
      Specific recommendations are provided for interventions designed to prevent and
      treat loneliness among older people.

PMID- 18728944
TI  - Intentions to seek (preventive) psychological help among older adults: an
      application of the theory of planned behaviour.
AB  - OBJECTIVES: This article examines the intentions to seek (preventive)
      psychological help among older persons. The study is carried out from the theory
      of planned behaviour and distinguishes attitudes (psychological openness),
      subjective norms (indifference to stigma), and perceived behavioural control
      (help-seeking propensity) in explaining behavioural intentions with regard to
      seeking preventive and therapeutic psychological help. METHOD: 167 Dutch adults
      between 65 and 75 years of age filled out a questionnaire measuring these
      concepts. RESULTS: Older adults have low intentions to seek professional help for
      psychological problems. Their intentions to use preventive help are somewhat
      higher. Older adults are rather indifferent to stigma and they perceive control,
      but they are less open to professional help when it comes to their own person.
      Regression analyses revealed that psychological openness and help-seeking
      propensity are related to intentions to seek preventive and therapeutic help.
      CONCLUSION: Older Dutch adults have stronger behavioural intentions to use
      preventive psychological help than to use therapeutic psychological help.
      Psychological openness is the main barrier for them to seek both forms of help.

PMID- 18728946
TI  - Predicting longitudinal patterns of psychological distress in older husband
      caregivers: further analysis of existing data.
AB  - Further analysis of existing data from a previous longitudinal study of older
      husband caregivers sought to determine whether primary objective and subjective
      stressors drawn from Pearlin's model of caregiving could predict three patterns
      of psychological distress observed in the sample over 1 year: (a) stable high
      (n=115), (b) stable low (n=44), and (c) rising (n=46). Results of discriminant
      function analyses show that subjective stressors (level of role overload, role
      captivity and relational deprivation) at baseline, distinguish the stable low
      group of husbands from the stable-high. The results suggest that there is
      considerable stability over time. Many husband caregivers report high
      psychological distress and need help, whereas there is a need of preventive
      interventions to keep psychological distress low. Implications for singular
      interventions that target specific factors according to group membership are
      discussed.

PMID- 18728948
TI  - Prevalence and predictors of depression among an elderly population of Pakistan.
AB  - OBJECTIVE: To assess the magnitude and risk factors of the problem of depression
      in an elderly population of Pakistan. METHOD: A cross-sectional study was
      conducted using a sample of 402 people aged 65 and above visiting the Community
      Health Center of the Aga Khan University, Karachi. Questionnaire based interviews
      were conducted for data collection and the 15-Item Geriatric Depression Scale was
      used to screen for depression. Univariate and multivariate logistic regression
      analyses were performed to identify factors associated with depression. RESULTS:
      Of the 402 participants; 69.7% (95% CI=+/-4.5%) were men, 76.4% (95% CI=+/-4.2%)
      were currently married, 36.8% (95% CI=+/-5%) had received 11 or more years of
      education and 24.4% (95% CI=+/-4.2%) were employed. The mean age was 70.57 years
      (SD=+/-5.414 years). The prevalence of depression was found to be 22.9% (95%
      CI=+/-4.1%) and multiple logistic regression analysis indicated that higher
      number of daily medications (p-value=0.03), total number of health problems (p
      value=0.002), financial problems (p-value<0.001), urinary incontinence (p
      value=0.08) and inadequately fulfilled spiritual needs (p-value = 0.067) were
      significantly associated with depressive symptoms. CONCLUSION: We have identified
      several risk factors for depression in the elderly which need to be taken into
      account by practicing family physicians and health care workers.

PMID- 18728945
TI  - The quality of medical care for comorbid conditions of depressed elders.
AB  - OBJECTIVES: In light of large variation in the quality of medical care, this
      study assesses the extent to which medical care for depressed elders is
      consistent with systematic quality standards. METHOD: Using the Donabedian model,
      we assess factors related to two quality measures: medical service fit and
      medical provider contact. We assessed 110 depressed older adults with comorbid
      conditions through practical guidelines of medical services. RESULTS: We found
      large variation in the quality of medical care and differences between two
      quality measures. Structure (Medigap insurance and clinical factors) and process
      factors (medical professional visits, ER visits, and adequacy of informal care)
      influenced the quality of medical care. CONCLUSION: Emphasizing accuracy in
      quality measures, quality disparities by medical conditions call attention to the
      risky population with certain conditions targeted for closer follow-up.
      Appropriate medical care processes can enhance the quality.

PMID- 18728947
TI  - Depressive symptoms in aged Chinese patients with silicosis.
AB  - OBJECTIVES: To investigate the prevalence of depressive symptoms in patients with
      silicosis and its determinants. METHODS: A cross-sectional cohort study was
      performed. About 121 patients with silicosis randomly selected from a case
      registry of a non-ferrous metal company and 110 controls completed the
      questionnaires of sociodemographic variables, Beck depression inventory (BDI) and
      lung function test. chi(2) test was performed to compare the prevalence of
      depressive symptoms between two groups. The relationship between the variables
      and depressive symptoms in patients with silicosis was assessed by performing the
      logistic regression analysis. RESULTS: Prevalence of depressive symptoms in
      patients with silicosis was 27.3%, which was higher than the figure 7.3% in
      controls (chi(2)=15.8, p<001). Severe respiratory symptoms, severe impaired
      physical function, FEV(1) <50% predicted and (FVC)% predicted less than mean were
      significantly associated with the depressive symptoms (Odds ratio [OR]=4.6, 5.9,
      3.0 and 5.2, respectively). CONCLUSION: High prevalence of depressive symptoms
      was found in patients with silicosis. Respiratory symptoms, physical function and
      pulmonary functions were associated with depressive symptoms. Our findings
      provide evidence for physicians to screen for depressive symptoms in patients
      with silicosis.

PMID- 18728952
TI  - Personality and health in Japanese older adults.
AB  - OBJECTIVE: Change versus stability of personality in late adulthood is an
      intriguing yet understudied issue. This cross-sectional study examined age and
      gender differences in Cloninger's biosocial model of personality, as well as
      their relation to health in a Japanese community sample whose age exceeds 50
      years. METHOD: Participants (N=330) completed the Temperament and Character
      Inventory and the General Health Questionnaire. MANOVA and hierarchical
      regression analyses were conducted. RESULTS: Age-related decreases in Reward
      Dependence, Self-Directedness, Cooperativeness, and an increase in Self
      Transcendence were found. Health was significantly predicted by Harm Avoidance
      and Self-Directedness. CONCLUSION: Personality change in late adulthood tends to
      occur in environmentally-based character, in a pattern of gradual social
      detachment and internal spiritual growth. Personality is a stronger predictor of
      health than demographic variables.

PMID- 18728949
TI  - Perceived stress and resilience in Alzheimer's disease caregivers: testing
      moderation and mediation models of social support.
AB  - OBJECTIVE: The study examined whether social support functioned as a protective,
      resilience factor among Alzheimer's disease (AD) caregivers. Moderation and
      mediation models were used to test social support amid stress and resilience.
      METHOD: A cross-sectional analysis of self-reported data was conducted. Measures
      of demographics, perceived stress, family support, friend support, overall social
      support, and resilience were administered to caregiver attendees (N=229) of two
      AD caregiver conferences. Hierarchical regression analysis showed the compounded
      impact of predictors on resilience. Odds ratios generated probability of high
      resilience given high stress and social supports. Social support moderation and
      mediation were tested via distinct series of regression equations. Path analyses
      illustrated effects on the models for significant moderation and/or mediation.
      RESULTS: Stress negatively influenced and accounted for most variation in
      resilience. Social support positively influenced resilience, and caregivers with
      high family support had the highest probability of elevated resilience.
      Moderation was observed among all support factors. No social support fulfilled
      the complete mediation criteria. CONCLUSION: Evidence of social support as a
      protective, moderating factor yields implications for health care practitioners
      who deliver services to assist AD caregivers, particularly the promotion of
      identification and utilization of supportive familial and peer relations.

PMID- 18728950
TI  - Wandering behaviour of persons with dementia in Korea: investigation of related
      factors.
AB  - OBJECTIVES: Despite being identified as a significant clinical phenomenon,
      wandering of persons with dementia (PWDs) has not been studied in Korea. As an
      initial trial, various factors chosen from the literature for their predictive
      relationships to wandering of Korean PWDs were evaluated in this study. METHOD: A
      total of 160 PWDs residing in 14 long-term care facilities participated in this
      study. The Mini-Mental State Exam (MMSE), Physical Activities of Daily Living
      (PADL) and Korean-translated Revised Algase Wandering Scale (Nursing Home
      version) (KRAWS-NH) were used to assess participants' degree of cognitive
      impairment, functional ability and wandering behaviour on six dimensions:
      persistent walking (PW), specific patterns (SP), spatial disorientation (SD),
      escape behaviour (EB), attention shift (AS) and negative outcomes (NO).
      Demographic, personal and environmental data were also collected. RESULTS: The
      MMSE score was a significant negative predictor for KRAWS-NH overall and
      subscales except for EB; while age, PADL and history of falls were positive
      predictors for SD and NO. Total number of residents in a room was a significant
      negative predictor for EB and AS. CONCLUSION: Different factors found in PWDs may
      contribute to different aspects of wandering behaviour. Further studies on
      factors influencing multiple facets of wandering in various cultural settings are
      warranted.

PMID- 18728955
TI  - Promoting older adults' well-being through Internet training and use. Response to
      Shapira et al.

PMID- 18728954
TI  - Outlooks for the future in independently living older Australians.
AB  - OBJECTIVES: To explore outlooks for the future which exist in an older
      population, through construction of a typology of combinations of absence or
      presence of reported hopes and fears for the future and a detailed analysis of
      the characteristics of older people in each of the four outlook categories
      created: optimistic, pessimistic, realistic or detached. METHODS: The findings
      are based on population survey responses from 8881 older Australians (65 + yr)
      living independently in the community. The Cochrane-Armitage test was used to
      detect the presence of trends, while logistic regression modelling was used to
      examine predictors of respondents expressing no main hope and/or no main fear.
      RESULTS: The logistic regression modelling identified predictors of outlook
      category, which have face validity and are consistent with the literature. In
      addition, the proportion of older people in the pessimistic category with scores
      indicating psychological distress (Kessler 6) was significantly higher than in
      the three other categories, providing support for the validity of the typology.
      CONCLUSION: The vast majority of independently living older Australians have
      realistic or optimistic outlooks about their future. The small minority who are
      pessimistic, and more likely to be experiencing psychological distress, can be
      identified through self-reported absence of hopes accompanied by presence of
      fears.

PMID- 18728951
TI  - Body satisfaction and retirement satisfaction: the mediational role of subjective
      health.
AB  - OBJECTIVES: Previous studies have highlighted the crucial role of subjective
      health in retirement satisfaction. However, it is likely that a retiree's health
      judgement mediates the influence of some variables on retirement satisfaction.
      The present study hypothesized that body satisfaction, as an evaluative summary
      of the individual's somatic experiences, is positively related to retirement
      satisfaction through the mediation of subjective health. METHOD: Retired
      individuals (N=256) were administered for body satisfaction, subjective health,
      and retirement satisfaction questionnaires. RESULTS: Regression analysis
      demonstrated that body satisfaction was positively related to retirement
      satisfaction through the partial mediation of subjective health. CONCLUSION: This
      study highlights the contribution of somatic experiences on retirement
      satisfaction, through their influence on retirees' health evaluation, and
      provides some additional insights into the determinants of life satisfaction in
      retirement.

PMID- 18728956
TI  - Editorial: Cleaning out the closet: getting ready for evidence-based practice.

PMID- 18728953
TI  - Professional carers' knowledge and response to depression among their aged-care
      clients: the care recipients' perspective.
AB  - Depression is an under-diagnosed disorder among the elderly, even in those who
      are in receipt of aged-care services. One factor associated with this under
      diagnosis has been identified as a reluctance amongst the elderly to discuss
      their mood and emotions with their medical practitioners. The current study
      focused on why depression is not recognised and acted on by those providing
      residential or home-based care to older people. We interviewed 15 elderly people
      residing in high-level or low-level aged-care facilities, and three elderly
      people who were receiving personal care in their homes. All participants had been
      identified by their care agencies as depressed. Participants reported their
      perceptions of their personal carers' knowledge and practices in managing the
      residents' depression. Although the participants described their carers in
      positive terms, they were critical of their knowledge and skills in recognising
      depression, and indicated that the communication between personal carers and care
      recipients about depressive symptomatology was seriously flawed. Training for
      personal carers in these areas, and efforts to change organisational culture are
      recommended.

PMID- 18728957
TI  - A review of pediatric HIV effects on neurocognitive development.
AB  - There are 2.3-million children infected with HIV worldwide. Medical advances and
      therapies have increased the life expectancy of HIV-infected children and
      improved their quality of life. This article reviews the HIV literature over the
      past 15 years related to children's development including: (1) the effects of HIV
      on the neurocognitive development of children; (2) the relationship between
      disease status and developmental functioning in HIV-infected children; and (3)
      the influence of the environmental context on HIV-infected children's
      development. As children with HIV continue to live longer, they will become a
      population of children with special needs. This paper reflects the current
      evidence of these needs and explores the interventions available to HIV-infected
      children.

PMID- 18728958
TI  - Pearls and pitfalls of community-based group interventions for adolescents:
      lessons learned from an adolescent asthma cAMP study.
AB  - This paper explores specific challenges in implementing community-based group
      interventions with adolescents and makes practical suggestions to researchers who
      contemplate the group approach. Group interventions have important implications
      for adolescent research and program development in the area of chronic illness.
      They have a capacity to address participants' psychosocial needs as well as to
      offer a cost and time-effective opportunity for disease-specific education. A
      group intervention encompasses an array of pragmatic challenges that need to be
      addressed through meticulous preparation. Based on the authors' firsthand
      experience with a group intervention for adolescents with asthma, this paper
      describes potential difficulties and logistics pertaining to recruitment,
      planning and implementation of a group intervention targeting adolescents and
      suggests general strategies that can be adopted.

PMID- 18728962
TI  - The rare entity of chronic lymphocytic leukemia in Chinese patients: is it the
      same disease as in Western patients?

PMID- 18728963
TI  - Surgery for nasal NK/T-cell lymphoma.

PMID- 18728965
TI  - Sustained remission and long-term survival of secondary central nervous system
      involvement by aggressive B-cell lymphoma after combination treatment of systemic
      high-dose chemotherapy and intrathecal rituximab.

PMID- 18728966
TI  - Successful treatment of partial graft failure after matched unrelated donor stem
      cell transplantation by a combination of ancestim (stem cell factor) and
      granulocyte colony stimulating factor in a patient with heavily pre-treated
      chronic lymphocytic leukemia.

PMID- 18728964
TI  - Growth control of multiple myeloma cells through inhibition of glycogen synthase
      kinase-3.
AB  - Anti-apoptotic pathways play a central role in the survival of multiple myeloma
      cells. The contribution of PI3-kinase and Akt kinase in mediating myeloma cell
      survival is well established although the role of glycogen synthase kinase-3
      (GSK3) is less defined. In this study we determined the contribution of GSK3 in
      growth regulation of myeloma cells. We treated six different multiple myeloma
      cell lines with a Thiadiazolidinone (TDZD), a non-competitive inhibitor of GSK3
      and determined its effects on proliferation and apoptosis. In addition we
      determined the activation of forkhead transcription factors (FOXO) in response to
      TDZD. TDZD inhibited proliferation and induced apoptosis of all myeloma cell
      lines. TDZD was also effective in inducing apoptosis of primary myeloma cells
      whereas CD34 positive normal hematopoietic cells were protected from apoptosis.
      Furthermore, TDZD-mediated inhibition of GSK3 resulted in dephosphorylation and
      activation of FOXO3a. In primary myeloma cells FOXO transcription factors were
      highly phosphorylated where as the levels of GSK3 phosphorylation was quite low.
      The levels of the pro-apoptotic proteins Fas ligand (FasL) and IkappaBalpha
      increased after treatment with TDZD in myeloma cell lines. These studies provide
      the basis for further testing of GSK3 inhibitors in the clinical setting.

PMID- 18728967
TI  - In vitro hepatic differentiation of human umbilical cord blood and bone marrow
      cells.
AB  - The purpose of the present study was to investigate whether human umbilical cord
      blood (UCB) as well as bone marrow (BM) can generate hepatocyte lineage cells in
      a simple culture condition. Mononuclear cells (MNCs) separated from UCB and BM
      were cultured in the presence of fibroblast growth factor (FGF)-1, FGF-2, stem
      cell factor (SCF), and hepatocyte growth factor (HGF). The cultured cells were
      analyzed for morphology and for the expression of mRNAs and/or proteins of
      hepatocyte lineage markers. Both the UCB and BM MNCs grown in the given culture
      condition yielded large, round cells that were adherent to the culture dishes. RT
      PCR analysis showed that mRNAs of albumin (ALB), cytokeratin (CK)-18, and alpha
      fetoprotein were expressed from day 7 in both the UCB- and BM-derived cells.
      Immunofluorescent staining showed that the large, round cells expressed not only
      ALB and CK-19 but also proliferating cell nuclear antigen, implying the
      proliferative potential of hepatocyte lineage cells. Therefore, UCB as well as BM
      can give rise to hepatocyte lineage cells in the simple culture condition with
      HGF, SCF, FGF-1, and FGF-2. These cells may be one of the potential candidates of
      cell sources for the cytotherapy of hepatic disease, although it remains to be
      determined if the hepatocyte lineage cells are derived from plastic hematopoietic
      stem cells or from liver stem cells that reside in UCB or BM.

PMID- 18728968
TI  - Dysplasia and disorder of cell membrane entirety in iron-deficiency anemia.
AB  - Peripheral blood smears of 43 patients (26 males, median age 18 months, range: 6
      180 months) with nutritional iron-deficiency anemia (IDA) were examined for the
      presence of trilineage hematological dysplasia. Twelve patients were reexamined
      for dysplastic findings after achieving a normal Hb and hematocrit level for age
      by the end of 2-3 months of iron treatment. A control group of 17 age-matched
      healthy children were also included. Neutrophils with loss of membrane entirety
      and protrusions were remarkable in 34/43 (79%) in the IDA group versus 1/12 (8%)
      after iron treatment and none of the control group. Microspherocytes were seen in
      9/43 (21%) of IDA patients. Additionally, trilienage dysplasia was observed in
      the bone marrow samples available in 3 of the patients. It has been shown that
      iron-deficiency results in cellular DNA and RNA alterations, cell-cycle G1/S
      phase arrest, and apoptosis. Rac GTPases have been shown to control actin
      cytoskeleton, influencing cell polarity, microtubule dynamics, and the
      cytoskeletal organization of hematopoietic cells. Thus, the findings described
      above in neutrophils and red cells suggest a plausible link between iron and the
      Rac GTPase gene family. It may be a new avenue for iron waiting for proof.

PMID- 18728969
TI  - Sensory neural hearing loss in beta-thalassemia major patients treated with
      deferoxamine.
AB  - This study evaluated the incidence of sensory neural hearing loss (SNHL) in beta
      thalassemia major patients treated with deferoxamine in Mofid Children's
      Hospital. Based on the patients' file review, this descriptive and cross
      sectional study was performed in all thalassemia patients older than 5 years old
      who were treated with regular blood transfusion and deferoxamine pump injection
      during the year 2006. The first visit with the otolaryngologist was performed in
      all patients to demarcate the presence of cerumen, otitis, and congenital
      abnormalities of ears. Then pure tone audiometery in frequency ranges of 250-8000
      Hz was performed. Data statistical analysis was done by Mann-Whitney, chi square,
      and Fisher tests. There were 67 patients over 5 years old in our study. Five
      patients (7.4%), including 2 boys and 3 girls, in the age range of 7-24 years
      (mean:17.8 +/- 6.6 years) had SNHL. Their hearing loss was bilateral and in the
      frequency range of 2000-4000 Hz, with a mean of 3200 +/- 836.66 Hz. There were no
      significant differences between SNHL and non-SNHL patients in age, sex, serum
      ferritin level, age of the first transfusion, starting age of deferoxamine
      infusion, or duration and dosage of deferoxamine therapy. It seems that SNHL is
      not directly related to the serum ferritin level or deferoxamine dosage and other
      factors, including genetic or constitutional characteristics, may be also
      related. On the other hand, this complication may occur with doses lower than 50
      mg/kg/day of deferoxamine, so no dosage can be considered safe for this drug.
      Despite the results of this study, hearing evaluation of beta-thalassemia major
      patients by audiometry is recommended because of the importance of this
      complication and the consequent disabilities.

PMID- 18728970
TI  - Recombinant human erythropoietin beta therapy: an effective strategy to reduce
      transfusion requirement in children receiving anticancer treatment.
AB  - In recent years erythropoietic agents have become important tools in the
      management of anemia in cancer patients, improving hemoglobin (Hb)
      concentrations, reducing the need for transfusion, and enhancing quality of life.
      In this prospective and historically controlled study, the effects of epoetin
      beta on Hb concentrations and red blood cell transfusion needs in children with
      cancer receiving chemotherapy or radiotherapy have been investigated. Epoetin
      beta (150 U/kg/day, 3 days a week) was given subcutaneously to 22 children with
      cancer when Hb concentration < or = 10 g/dL. Data from these patients were
      compared with those from 20 historical control patients. Hb concentrations were
      studied weekly in the first 9 weeks, then weekly or fortnightly thereafter.
      Minimum, maximum, and mean Hb concentrations, frequency of red blood cell
      transfusion, and the number of red cell packs given were noted. Hb concentrations
      in weeks 6, 8, and 11 were clearly higher in the study group than the controls.
      The minimum Hb concentration of the study group was significantly higher than
      than the control group (7.98 +/- 0.73 [6.70-9.68] g/dL and 7.24 +/- 1.40 [5.50
      11.20] g/dL, respectively [p = .038]). A total of 8 units of erythrocyte
      suspension was given to 4 of the 22 patients in the epoetin group (0.36 unit per
      patient), while 16 of the 20 patients in the control group received 37 units of
      erythrocyte suspension in total (1.85 units per patient). The red cell
      transfusion requirement and the units of transfused erythrocytes per patient were
      clearly lower in the epoetin group (p < .001 for both of the parameters). No drug
      related side effects were noted during epoetin therapy. Epoetin beta therapy
      provides significant increase in Hb concentrations in children with cancer under
      anticancer treatment, especially after the sixth week of therapy. Administration
      of epoetin beta prevents profound decreases in Hb concentrations in the course of
      therapy and effectively reduces the need for red blood cell transfusions. Epoetin
      beta was found to be safe and effective in the dosage and the scheme it was used
      in our study.

PMID- 18728971
TI  - Pilomatricoma in children: a frequently misdiagnosed superficial tumor.
AB  - Pilomatricomas are the most common superficial tumors in children, but they are
      frequently misdiagnosed preoperatively. There are some characteristic features of
      pilomatricomas that can help clinicians differentiate it from other tumors. The
      authors report 3 children with head and neck pilomatricomas, one with multiple
      tumors. They emphasize some clinical features that may help in differential
      diagnosis to avoid unnecessary investigations before surgical removal.

PMID- 18728972
TI  - Immunohistochemical analyses of phosphatases in childhood B-cell lymphoma: lower
      expression of PTEN and HePTP and higher number of positive cells for nuclear SHP2
      in B-cell lymphoma cases compared to controls.
AB  - Although many pediatric B-cell lymphoma patients are being cured today, much is
      still unknown about the pathogenesis of this disease. Protein tyrosine
      phosphatases are involved in the control of survival, growth, and differentiation
      of cells. The authors have analyzed 26 pediatric B-cell lymphoma cases for the
      expression of a panel of phosphatases and report a statistically significant
      lower expression intensity of PTEN and HePTP and higher nuclear SHP2 expression
      in B-cell lymphoma cases compared to lymphoid tissue. Knowledge about the
      expression of key regulatory proteins in pediatric B-cell lymphomas is necessary
      for revealing the complex molecular background of this disease.

PMID- 18728973
TI  - Prenatal diagnosis of beta-thalassemia in Egypt: implementing accurate high-tech
      methods did not reflect much on the outcome.
AB  - The clinical severity of thalassemia major makes it a priority genetic disease
      for prevention programs through prenatal diagnosis for carrier couples.
      Incorporation of automated DNA sequencing that enables the characterization of
      mutations not detected by other mutation specific detection procedures was a
      prime goal of this work. Automated DNA sequencing was offered on fetal tissues in
      30 pregnancies during the year 2005. The pregnancies were at high risk for
      homozygosity or compound heterozygosity for beta-thalassemia based on mutation
      analysis of both parents before prenatal diagnosis. Both parents have beta
      thalassemia trait. Fetal samples were collected by chorionic villus sampling
      (CVS) in the first trimester and by amniocentesis in the second trimester. The
      point mutations were characterized by PCR (ARMS). The absence of the expected
      fragment with all the mutant ARMS primers insinuated an uncharacterized DNA
      segment that was further subjected to direct automated fluorescent DNA sequencing
      in an attempt to know if the fetus was affected by parents' mutations. If no
      mutation was detected using the PCR ARMS, the sample was further analyzed using
      direct automated fluorescent DNA sequencing. The mean gestation when carrying out
      the invasive procedure was 14 (10 -18) weeks. All mothers had a previous affected
      pregnancy, and 13 had two or more previous affected pregnancies. Pregnancies
      were: 8 carrier fetuses (trait) and 22 affected fetuses in which 2 were
      homozygous and 20 double heterozygous. Fourteen parents of affected fetuses
      preferred to continue pregnancy and the babies were born as diagnosed. The other
      8 parents decided on termination and DNA of the abortuses proved to be as
      previously diagnosed by DNA sequencing. The use of PCR amplification and direct
      sequencing have permitted the accurate characterization of unidentified alleles
      and successfully solved 100% of the examined samples. However, it has resulted in
      minor changes of the outcome as the majority of couples preferred continuation of
      pregnancy.

PMID- 18728974
TI  - Enhanced effect of IFNgamma on the induced apoptosis of neuroblastoma cells by
      cytotoxic drugs.
AB  - The objective of this study was to explore the antitumor effects of cytotoxic
      drugs combined with IFNgamma on neuroblastoma cell line SH-SY5Y cells. The
      expression of caspase 8 mRNA and protein was detected with RT-PCR and Western
      blot analysis. The effects of cytotoxic drugs and IFNgamma combined with
      cytotoxic drugs on the growth and apoptosis of SH-SY5Y cells were detected with
      the methods of MTT and flow cytometry. Caspase 8 activity was measured by
      colorimetric assay. Caspase 8 was undetectable in SH-SY5Y cells with an increased
      expression of caspase 8 after the treatment of IFNgamma. SH-SY5Y cells were
      sensitive to Adriamycin relatively but resistant to TNFalpha and TRAIL, while
      IFNgamma-pretreated SH-SY5Y cells were more sensitive to the cytotoxic drugs with
      an increase of caspase 8 activity. The authors conclude that IFNgamma can
      sensitize SH-SY5Y cells to Adriamycin-, TNFalpha-, and TRAIL-induced apoptosis
      and this may be realized by the upregulation of caspase 8.

PMID- 18728975
TI  - Dermatofibrosarcoma protuberans in childhood: two case reports and review of the
      literature.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer with intermediate
      malignancy, characterized by a progressive local growth and a propensity for
      local recurrence. DFSP is most frequent in adults; however, in recent years, DFSP
      in childhood emerged to be more common than previously believed. Unfortunately
      DFSP in children may be misdiagnosed, leading to a delay in the treatment. The
      authors report two cases of childhood DFSP with unusual clinical presentation: a
      congenital nodular variant and an atrophic variant developed at 2 years of age,
      both with acral localization. They highlight the importance of an early diagnosis
      by pediatricians and dermatologists to ensure an appropriate complete excision
      and reduce the risks of recurrences.

PMID- 18728977
TI  - Bone marrow findings in juvenile idiopathic arthritis.
AB  - The diagnosis of juvenile idiopathic arthritis (JIA) is an exclusion one due to
      heterogeneous clinical presentation and lack of specific laboratory tests. The
      authors investigated bone marrow of 25 untreated children with JIA at the onset
      of the disease. Bone marrow smears were evaluated for cell populations as well as
      myelodysplastic features and compared to two control groups. The characteristic
      of bone marrow in JIA was myeloid hyperplasia and elevated plasmocyte count.
      There was no difference between JIA patients and control groups in terms of
      myelodysplastic features. These findings can be helpful in explaining
      hematological alterations in JIA.

PMID- 18728976
TI  - Radiological evaluation of patients with pituitary langerhans cell histiocytosis
      at diagnosis and at follow-up.
AB  - This study evaluated pituitary imaging findings in 13 patients with Langerhans
      cell histiocytosis (LCH) with diabetes insipidus. Nine patients were evaluated
      with pituitary magnetic resonance imaging (MRI), 3 with brain computed
      tomography, and 1 with brain MRI. The infundibulum was thickened in 11 (84.6%)
      patients, thread-like in 1 (7.7%), and normal in 1 (7.7%). Posterior pituitary
      intensity was absent in 10 patients (76.9%); in 4 patients, the pituitary gland
      was small in size, and 2 patients had atrophic pituitary. Three had a small
      sella. Infundibular thickening and absence of posterior pituitary intensity were
      the most common radiological findings. MRI imaging should be used to follow up
      patients with pituitary histiocytosis, and patients with LCH and diabetes
      insipidus should be followed for pituitary atrophy.

PMID- 18728978
TI  - RUNX1 aberrations in ETV6/RUNX1-positive and ETV6/RUNX1-negative patients: its
      hemato-pathological and prognostic significance in a large cohort (619 cases) of
      ALL.
AB  - A large-cohort study (619) of acute lymphoblastic leukemia (ALL) revealed an
      ETV6/RUNX1 (previously known as TEL/AML1) incidence of 18% in pediatric B-cell
      precussor ALL, indicating no geographical heterogeinity. Association of CD34
      negative phenotype, peak incidence in the 3- to 7-year age group, and a
      comparatively low frequency of ETV6 homologue loss in ETV6/RUNX1-positive cases
      were distinct findings in this series. Additional genetic changes, such as ETV6
      loss, extra RUNX1, ETV6/RUNX1 duplication, and MLL aberrations in the ETV6/RUNX1
      positive group, supported the hypothesis of the ETV6/RUNX1 leukemogenic model
      that these secondary changes are necessary for leukemogenesis rather than
      progression of disease. This study disclosed RUNX1 alterations in the ETV6/RUNX1
      negative group of BCP-ALL that encourages the investigation of RUNX1 at a large
      scale with longer follow-up, which will focus on the prognostic importance and
      the underlying biology of disease.

PMID- 18728979
TI  - Pulmonary function test in transfusion-dependent beta-thalassemia patients.
AB  - Beta-thalassaemia is the most common hemoglobinopathies in our region with
      treatment of regular blood transfusion. Iron overload and hemosiderosis can cause
      organ involvement. Recent studies have focused on pulmonary involvement and
      pathophysiology of lung damage. The goal of this study was to investigate the
      pulmonary abnormalities in thalassemic patients in relation with sign and
      symptoms and iron overload. The authors studied pulmonary function test (PFT) at
      the Adult Thalassemia Clinic in Tehran. The history of blood transfusion, iron
      chelation, respiratory problems, and drug usage was taken. Physical examination,
      PFT, arterial blood gas (ABG), and chest X-ray (CXR) were done. In total, 139
      patients were studied. The mean age was 21.1 years and mean duration of
      transfusion was 18 years. It was found that 133 patients (95.7%) did not have
      respiratory problems and only 6 (4.3%) had some respiratory complaints. In CXR,
      100 patients (89.3%) had normal lung pattern and others (10.7%) had variable
      degrees of abnormal lung pattern. In ABG, mean of Po(2) was 73.5% and mean of
      O(2) saturation was 90.6%. In PFT, 101 patients (72.7%) had restrictive pattern,
      35 (25.1%) had normal pattern, and 3 (2.2%) had combined pattern. According to
      vital capacity, the patients were placed in five categories: 54 patients (38.8%)
      normal, 37 (26.6%) mild, 35 (25.3%) moderate, 10 (7.2%) severe, and 3 (2.1%)
      extremely severe pulmonary deficit. There was no statistical significance between
      PFT results with all variables studied, except duration of blood transfusion,
      which may be considered a indirect effect of iron load (p = .05, r = .361).
      According to these results, restrictive pattern was the most common finding
      (72.7%) in PFT, while 95.7% of patients had no respiratory complaint, and in the
      chest X-ray group, 89.3% had normal pattern. The authors conclude that the lung
      may be considered a site for organ damage, and alteration of pulmonary function
      may be expected in transfusion-dependent patients in spite of no pulmonary
      symptoms or normal CXR. In recent years, because of new iron chelating drugs,
      doctors can expect thalassemic patients to have a long life-time and need to
      increase their quality of life. One way to do this is to evaluate the respiratory
      system by PFT to prevent the squeal of pulmonary disease.

PMID- 18728980
TI  - Isolated relapse of acute lymphoblastic leukemia in the breast of a young female.
AB  - A 20-year-old female developed a relapse of B-precursor acute lymphoblastic
      leukemia (ALL) as a mass in her left breast after 6 years of maintained
      continuous complete remission. No leukemic lesions were identified in other sites
      such as the bone marrow or cerebrospinal fluid. The relapsed leukemic cells in
      the breast revealed the same immunophenotypes (CD10(+), CD19(+), CD20(+), HLA
      DR(+), CD34(+)) as those of the onset ALL cells in the bone marrow. A literature
      survey found 10 other cases of ALL relapse in the breast without bone marrow
      involvement, mostly consisting of adolescent girls. Including the present report,
      a total of 11 cases were analyzed; the onset ages of ALL were a median of 16.5
      (range 5-50) years old and the ages of relapse in the breast a median of 20
      (range 12-51) years old. Data suggest that, although rare, the breast could
      become one of the extramedullary relapse sites of ALL developed in adolescent
      girls.

PMID- 18728981
TI  - Lymphangiomatosis in a child: eight years' follow-up without treatment.
AB  - Lymphangiomatosis of the spleen with diffuse lymphangiomatosis of the bone is
      extremely rare and there is no consensus about management at present. Here, the
      authors report a child presenting initially with back pain and diagnosed as
      lymphangiomatosis on several sites throughout the bony structures and the spleen.
      The patient is in a stable state at the end of 8 years without any treatment. The
      authors also discuss the follow-up option that may be considered as a strategy
      for management.

PMID- 18728983
TI  - HIV risk exposure among South African children in public health facilities.
AB  - The study investigates the risk exposure to HIV infection among South African
      children aged 2-9 years served by public health services. Together with their
      biological mothers, 3471 children and were recruited from inpatient and
      outpatient children in the Free State Province. Blood samples were taken by
      professional nurses and a history taken of exposure factors associated with HIV
      transmission. DNA testing was used to confirm biological maternity where the
      child was HIV-positive and the mother HIV-negative. Mother-child pairs were
      stratified by mother's HIV status. Exposure factors related to the child's HIV
      status were examined in each stratum using a chi-square test. Independent factors
      were then included in a multiple logistic regression model. Having an HIV
      positive mother was strongly related to HIV infection in children (OR: 310;
      95%CI: 148-781). However, seven HIV-positive children had HIV-negative mothers.
      Transmission in this group was significantly associated with breastfeeding by a
      non-biological mother (OR: 437; 95%CI: 53-5020), being fed with expressed breast
      milk from a milk room (OR: 37.6; 95%CI: 6.2-259.0), dental injection history (OR:
      31.5; 95%CI: 4.5-189.4) and visits to a dentist (OR: 26.9; 95%CI: 4.4-283.5).
      Although mother-to-child-transmission is shown to be the primary mode of HIV
      transmission in South African children, the few HIV-positive children infected by
      other modes of transmission suggest a potential risk of non-vertical HIV
      infections. These infections can be prevented through education and improved
      infection-control procedures.

PMID- 18728984
TI  - Exploring HIV risk perception and behaviour in the context of antiretroviral
      treatment: results from a township household survey.
AB  - The objective of this cross-sectional household survey was to assess factors
      influencing HIV risk perception, behaviour and intervention uptake in a community
      characterised by high HIV prevalence and availability of antiretroviral therapy
      (ART). The survey was conducted in Khayelitsha, South Africa and involved two
      stage sampling with self-weighting clusters and random selection of households
      within clusters. One man and woman between 14 and 49 years old was interviewed in
      each household; 696 men and 879 women were interviewed for a response rate of 84%
      and 92% respectively. Ninety-three percent and 94% were sexually active with
      median age of sexual debut 15.3 and 16.5 years. Eighty-three percent and 82%
      reported a partner at the time of interview and 29% and 8% had additional
      partner(s). Forty-one percent and 33% reported condom use during the last sexual
      encounter. Thirty-seven percent of men not using condoms did not as they believed
      their partner to be faithful, whilst 27% of women did not as their partner
      refused. Twenty-eight percent and 53% had been tested for HIV. Having undergone
      HIV testing was not associated with condom usage, whilst current relationship
      status was the strongest association with condom usage for both men and women. In
      spite of a relatively high uptake of condoms and testing as well as ART
      availability, the HIV epidemic has continued unabated in Khayelitsha. Even
      greater coverage of preventive interventions is required, together with a
      national social and political environment that builds on the availability of both
      preventive and treatment services.

PMID- 18728985
TI  - Condom use and self-efficacy among female sex workers with steady partners in
      China.
AB  - This study attempted to determine the association of self-efficacy with condom
      use practice and to explore reasons of not using condoms among female sex workers
      (FSWs) with steady partners in China. Data from 309 establishment-based FSWs with
      steady partners in one Chinese county were collected through a cross-sectional
      study. Consistent condom use with steady partners was lower than with clients in
      entertainment establishments. Condom-use self-efficacy was positively associated
      with condom-use communication and condom-use frequency with clients but not with
      steady partners. It was positively associated with condom-use intention and skill
      with clients and steady partners. However, it was not associated with appropriate
      use of condoms. Significant differences of reasons about not using condom were
      also observed between the two partner types. The results may represent an
      important challenge to STD and HIV intervention programs aimed at achieving
      consistent condom use in FSWs. Health workers should focus on psychosocial
      factors affecting inconsistent condom use among FSWs with steady partners in
      China. In addition, intervention programs that can promote FSWs' self-efficacy
      through condom-use skill training will still be necessary.

PMID- 18728986
TI  - Patterns of condom acquisition and its association with consistent use among
      young men in Nigeria.
AB  - There is limited information about the influence of condom acquisition patterns
      on consistent condom use. Research is required to identify the relative extent of
      consistent condom use among individuals who always obtain condoms free, or who
      always have mixed procurement of free and purchased condoms or who always
      purchase condoms. The study analysed condom acquisition and sexual behaviour
      practices of 372 young men and logistic regression was analysed to determine
      whether condom acquisition practice was a predictor of consistent condom use.
      Results showed that most participants (41%) had mixed procurement of free and
      purchased condoms, 31% always bought condoms while 28% always purchased condoms.
      Majority of individuals (71%) who always purchased condoms, 23% who had mixed
      procurement, and 12% who had free condoms consistently used condoms. The results
      also showed that having 2 or more partners and always purchasing condoms
      increased the likelihood of consistent condom use. It is recommended that
      programmes of free condom supply should also incorporate in it education that
      emphasizes consistent condom use with a partner whose HIV sero status is not
      known.

PMID- 18728987
TI  - Sustained antiretroviral treatment adherence in survivors of the pre-HAART era:
      attitudes and beliefs.
AB  - The objective of this study was to assess adherence of HIV-1-infected patients
      who started treatment in the pre-HAART era and to determine variables associated
      with better adherence, including relevant attitudes and beliefs. This is a cross
      sectional study enrolling patients who had received antiretroviral therapy for
      >or=10 years. Adherence was evaluated through self-reporting and plasma drug
      concentrations. Treatment variables, attitudes and beliefs were collected during
      structured interviews. The results show that for 87 patients the median
      (interquartile range) time on therapy was 13 (10-19) years; 80 were on therapy at
      the time of analysis. Adherence was >or=95% in 54 patients (67.5%), 90-94% in 22
      (27.5%) and <90% in 4 (5%). Drug concentrations were below the lower limit of
      detection in five patients. Younger age (p=0.014), female gender (p=0.005),
      current substance abuse (p=0.004) and hepatitis C virus co-infection (p<0.001)
      were related to lower adherence. Adherence did not differ in relation to
      different drug families or once- or twice-daily regimens. Patients with adherence
      <95% were more likely to have interrupted treatment without doctor's
      recommendation (p=0.009). Adherent patients exhibited a higher perception of risk
      of developing the illness and of benefits of therapy, higher self-efficacy and
      intention to adhere and were more influenced by events that motivate medication
      intake. To conclude, adherence was >90% in most patients on antiretroviral
      therapy for >or=10 years. Adherence was more related to beliefs about health and
      illness than to the characteristics of medication or level of knowledge about
      treatment. Care adherence interventions should include assessment of health
      beliefs.

PMID- 18728988
TI  - Rehearsal strategy use in Alzheimer's disease.
AB  - Memory strategy usage and awareness of memory performance are both crucial for
      memory rehabilitation. We explored Alzheimer's patients' ability to apply and
      control learning strategies and also their ability to predict the effect of these
      strategies on subsequent performance. In a rehearsal condition, participants were
      explicitly asked to overtly rehearse words and were given as long as they liked
      at study. In a control condition, participants read the words passively at a
      fixed presentation rate. In all groups, recall was superior in the rehearsal
      condition than in the reading condition. Alzheimer's patients showed different
      strategy usage. Overall, people with Alzheimer's disease spend longer studying to
      be-remembered words under unpaced conditions, but they do not use this time to
      rehearse to the same extent as controls. We hypothesize that this failure to
      rehearse could be based on the inability to use effortful executive mechanisms
      involved during study.

PMID- 18728989
TI  - Thermotolerant hydrogenases: biological diversity, properties, and
      biotechnological applications.
AB  - Hydrogenases are metalloproteins that catalyze the oxidation and reduction of
      molecular hydrogen and play a crucial role in many microbial metabolic processes.
      A subset of hydrogenases capable of functioning at temperatures from 50 to 125
      degrees C is found in thermophilic microorganisms. Most known thermotolerant
      hydrogenases contain a [NiFe] active site and are either bidirectional or uptake
      type. Although no exhaustive survey has been done of the ecological diversity of
      thermophilic hydrogen-reducing or oxidizing bacteria, they appear to exist in
      virtually every thermophilic environment examined to date. Thermotolerant
      hydrogenases share many similarities with their mesophilic counterparts, but they
      have several features in addition to thermotolerance that make them especially
      well suited for biotechnological applications. Ongoing research is focused on
      potential applications of thermotolerant H2 ases in biosynthesis, H2 production,
      bioremediation, and biosensors.

PMID- 18728990
TI  - Pneumococcal surface adhesin A (PsaA): a review.
AB  - Pneumococcal surface adhesin A (PsaA) is a surface-exposed common 37-kilodalton
      multi-functional lipoprotein detected on all known serotypes of Streptococcus
      pneumoniae. This lipoprotein belongs to the ABC-type transport protein complex
      that transports Mn2+; it is also an adhesin that plays a major role in
      pneumococcal attachment to the host cell and virulence. PsaA is immunogenic and
      natural nasopharyngeal colonization of pneumococci elicits an increase in
      antibody towards PsaA. Hence, PsaA is being actively evaluated as a component of
      a vaccine in formulations composed of pneumococcal common proteins. PsaA has been
      expressed as an E. coli recombinant protein, purified, and evaluated in a phase
      one clinical trial. This article reviews PsaA, its structure and role in
      pneumococcal virulence, immunogenicity, and potential to reduce nasopharyngeal
      colonization (a major prerequisite for pneumococcal pathogenesis) as a component
      of a common pneumococcal protein vaccine.

PMID- 18728991
TI  - Ecology of E. coli O157:H7 and Salmonella enterica in the primary vegetable
      production chain.
AB  - There is an increased concern that plants might be more important as a carrier
      for human enteric pathogens like E. coli O157:H7 and Salmonella enterica serovars
      than previously thought. This review summarizes the knowledge available on the
      ecology of E. coli O157:H7 and Salmonella enterica in the primary production
      chain of leafy green vegetables (in particular lettuce), including manure, manure
      amended soil, and crop. Based on the available literature, suggestions are made
      for the control of these pathogens. The suggested approach of oligotrophication
      of agro-ecosystems fits in the wider approach to lower environmental emissions of
      nutrients from manure application and to enhance the suppression against plant
      pathogens.

PMID- 18728992
TI  - Recovery from welding-fume-exposure-induced MRI T1 signal intensities after
      cessation of welding-fume exposure in brains of cynomolgus monkeys.
AB  - The shortening of the MRI T1 relaxation time, indicative of a high signal
      intensity in a T1-weighted MRI, is known as a useful biomarker for Mn exposure
      after short-term welding-fume exposure. A previous monkey experimental study
      found that the T1 relaxation times decreased time-dependently after exposure, and
      a visually detectable high signal intensity appeared after 150 days of exposure.
      The nadir for the shortening of the T1 relaxation time was also previously found
      to correspond well with the blood Mn concentration in welders, suggesting a
      correlation between a prolonged high blood Mn concentration and shortened T1
      relaxation time. Accordingly, to clarify the clearance of the brain Mn
      concentration after the cessation of welding-fume exposure, cynomolgus monkeys
      were assigned to 3 groups-unexposed, low dose (31 mg/m(3) total suspended
      particulate (TSP), 0.9 mg Mn/m(3)), and high dose (62 mg/m(3) TSP, 1.95 mg
      Mn/m(3))-and exposed to manual metal-arc stainless steel (MMA-SS) welding fumes
      for 2 h per day for 8 mo in an inhalation chamber system equipped with an
      automatic fume generator. After reaching the peak MRI T1 signal intensity
      (shortest T1 relaxation time), the monkeys were allowed to recover by ceasing the
      welding-fume exposure. Within 2 mo, the MRI T1 signal intensities for the exposed
      monkeys returned to nearly the same level as those for the unexposed monkeys,
      indicating the potential for recovery from a high MRI T1 signal intensity induced
      by welding-fume exposure, even after prolonged exposure. Clearance of the Mn
      tissue concentration was also demonstrated in the globus pallidus, plus other
      tissues from the brain, liver, spleen, and blood. In contrast, there was no
      clearance of the lung concentrations of Mn, indicating that a soluble form of Mn
      was transported to the blood and brain. Therefore, the solubility of Mn in
      welding fumes would appear to be an important determinant as regards the
      retention of blood Mn levels and brain tissue Mn concentrations in welders.

PMID- 18728993
TI  - Evaluation of trigeminal sensitivity to ammonia in asthmatics and healthy human
      volunteers.
AB  - Asthmatics often report the triggering or exacerbation of respiratory symptoms
      following exposure to airborne irritants, which in some cases may result from
      stimulation of irritant receptors in the upper airways inducing reflexive
      bronchoconstriction. Ammonia (NH3) is a common constituent of commercially
      available household products, and in high concentration has the potential to
      elicit sensory irritation in the eyes and upper respiratory tract of humans. The
      goal of the present study was to evaluate the irritation potential of ammonia in
      asthmatics and healthy volunteers and to determine whether differences in nasal
      or ocular irritant sensitivity to ammonia between these two groups could account
      for the exacerbation of symptoms reported by asthmatics following exposure to an
      irritant. Twenty-five healthy and 15 mild/moderate persistent asthmatic
      volunteers, with reported sensitivity to household cleaning products, were
      evaluated for their sensitivity to the ocular and nasal irritancy of NH3. Lung
      function was evaluated at baseline and multiple time points following exposure.
      Irritation thresholds did not differ between asthmatics and healthy controls, nor
      did ratings of odor intensity, annoyance, and irritancy following exposure to NH3
      concentrations at and above the irritant threshold for longer periods of time (30
      s). Importantly, no changes in lung function occurred following exposure to NH3
      for any individuals in either group. Thus, despite heightened symptom reports to
      environmental irritants among asthmatics, the ocular and nasal trigeminal system
      of mild to moderate asthmatics does not appear to be more sensitive or more
      reactive than that of nonasthmatics, nor does short-duration exposure to ammonia
      at irritant levels induce changes in lung function. At least in brief exposures,
      the basis for some asthmatics to experience adverse responses to volatile
      compounds in everyday life may arise from factors other than trigeminally
      mediated reflexes.

PMID- 18728994
TI  - Butyrylcholinesterase inhibitory activity of testosterone and some of its
      metabolites.
AB  - Testosterone and ten of its metabolites were examined as inhibitors of
      butyrylcholinesterase. A significant enzyme inhibition activity (IC(50) = 1.55
      microM) was observed for androst-4-en-3,7-dione. The kinetic parameters of
      butyrylcholinesterase inhibition were determined and molecular docking was
      carried out in order to develop a better understanding of the inhibitor-enzyme
      interactions. The results showed that the inhibition was non-competitive,
      stabilized mainly by hydrogen bonds and hydrophobic interactions between the
      inhibitor and butyrylcholinesterase.

PMID- 18728995
TI  - Stabilizing effect of cetostearyl alcohol and glyceryl monostearate as co
      emulsifiers on hydrocarbon-free O/W glyceride creams.
AB  - The structure of a stable O/W cream is characterized by a more or less pronounced
      mixed crystal bilayer. The addition of co-emulsifiers in order to achieve a soft
      formulation often leads to a mixed crystal bilayer network of high viscosity and
      even phase separation. In order to ovoid this components of different chemical
      identities are used which often are not inert or harmless if they are absorbed.
      For this reason it seems to be interesting to use only components from one
      chemical family, e.g. to use only glycerides and their derivatives because in the
      case of absorption they are metabolized. The disadvantages of glyceride creams
      are, however, their low viscosity. The aim of this investigation was to find the
      optimum amount of co-emulsifier as consistency excipient for the basic
      formulation of an O/W glyceride cream. This was achieved by using differential
      scanning calorimetry; thermogravimetry, oscillation rheology and various stress
      tests. The amount of co-emulsifier used should not be too high, as it would
      crystallize increasingly during storage which gives the preparation an optical
      inhomogenity and a lack in softness which is needed for a suitable cosmetic
      acceptance. A slightly higher concentration than is necessary for the mixed
      emulsifier system can be advantageous, as the formation of a separate crystalline
      lipophilic network in the preparation increases its viscosity which will lead to
      a higher physico-chemical stability of the formulation. These results were
      obtained with the co-emulsifiers glyceryl monostearate (Imwitor 900),
      cetylstearyl alcohol (Lanette O), and PEG-20-glycerolstearate (Tagat S2) as O/W
      emulsifier. As oil phase a mixture of Miglyol 812 (caprylic/capric triglyceride)
      and Avocado oil was used.

PMID- 18728996
TI  - Simulation of roller compaction with subsequent tableting and characterization of
      lactose and microcrystalline cellulose.
AB  - Tablets are by far the most common solid oral dosage forms, and many drugs need
      to be granulated before they can be tableted. Increasingly roller compaction is
      being used as a dry granulation technique; however it is a very time and material
      intensive method. Thus some mini roller compactors and simulations of the roller
      compaction process have been developed as a means of studying the technique at
      small scale. An important factor in the selection of materials for roller
      compaction is their ability to be recompressed into tablets after the initial
      roller compaction and milling steps. In this paper the roller compaction process
      was simulated on the basis of some models by Gereg and Cappola (2002) and Zinchuk
      et al. (2004). An eccentric tableting machine was used to make compacts from
      alpha-lactose monohydrate, anhydrous beta-lactose, spray-dried lactose and
      microcrystalline cellulose at different maximum relative densities (rho rel,max
      0.6-0.9). These compacts were milled immediately to granules with a rotary
      granulator. The properties of the granules were analyzed and compared to the
      properties of the original powders. These granules and powders were then tableted
      at different maximum relative densities (rho rel,max 0.75-0.95) and their
      properties including elastic recovery, crushing force and 3D-model were analyzed.
      The properties of the tablets made from the granules were compared to the
      properties of the tablets made from the powders to determine which excipients are
      most suitable for the roller compaction process. The study showed that anhydrous
      beta-lactose is the preferred form of lactose for use in roller compaction since
      compaction did not affect tablet crushing force to a large extent. With the
      simulation of roller compaction process one is able to find qualified materials
      for use in roller compaction without the necessity of a great deal of material
      and time.

PMID- 18728997
TI  - Single-probe serial position recall: evidence of modularity for olfactory,
      visual, and auditory short-term memory.
AB  - The present study examined and compared order memory for a list of sequentially
      presented odours, unfamiliar faces, and pure tones. Employing single-probe serial
      position recall and following a correction for a response bias, qualitatively
      different serial position functions were observed across stimuli. Participants
      demonstrated an ability to perform absolute order memory judgments for odours.
      Furthermore, odours produced an absence of serial position effects, unfamiliar
      faces produced both primacy and recency, and pure tones produced recency but not
      primacy. Such a finding is contrary to the proposal by Ward, Avons, and Melling
      (2005) that the serial position function is task, rather than modality,
      dependent. In contrast, the observed functions support a modular
      conceptualization of short-term memory (e.g., Andrade & Donaldson, 2007; Baddeley
      & Hitch, 1974), whereby separate modality-specific memorial systems operate. An
      alternative amodal interpretation is also discussed wherein serial position
      function disparities are accommodated via differences in the psychological
      distinctiveness of stimuli (Hay, Smyth, Hitch, & Horton, 2007).

PMID- 18728998
TI  - The influence of task characteristics on younger and older adult motor overflow.
AB  - This study investigated the influence of attentional and motor demands on motor
      overflow in 17 healthy young (18-35 years) and 17 older adults (60-80 years).
      Participants performed a finger pressing task by exerting either 33% or 66% of
      their maximal force output using their dominant or nondominant hand. Overflow was
      concurrently recorded in the passive hand. Attention was manipulated via a
      tactile stimulus presented to one or both hands for certain trials. Results
      showed that older adults exhibited greater overflow than young adults and that
      the effect of target force was exacerbated in older adults. Further, only older
      adult overflow was increased when tactile stimulation was directed to one or both
      hands. Increased overflow in older adults may result from bilateral cortical
      activation that is influenced by increased task demands. To perform comparatively
      to younger adults, older adults may compensate for age-related brain changes by
      recruiting an increased cortical network.

PMID- 18728999
TI  - Dissociation between appearance and location within visuo-spatial working memory.
AB  - Previous research has demonstrated separation between systems supporting memory
      for appearance and memory for location. However, the interpretation of these
      results is complicated by a confound occurring because of the simultaneous
      presentation of objects in multiple-item arrays when assessing memory for
      appearance and the sequential presentation of items when assessing memory for
      location. This paper reports an experiment in which sequential or simultaneous
      modes of presentation were factorially manipulated with memory for visual
      appearance or memory for location. Spatial interference (tapping) or visual
      interference (dynamic visual noise) were presented during retention. Appearance
      versus location interacted with the type of interference task, but mode of
      presentation did not. These results are consistent with the view that different
      subsystems within visuo-spatial working memory support memory for appearance and
      memory for location.

PMID- 18729000
TI  - The development of novel anti-hyperlipidemic drugs: a tough business gets
      tougher.

PMID- 18729001
TI  - HDL: still a target for new therapies?
AB  - Residual cardiovascular risk despite lowering LDL-cholesterol has stimulated
      research to develop strategies that promote the protective properties of HDL
      cholesterol. Population and animal studies have suggested that HDL plays an
      important role in protection against cardiovascular disease. As a result,
      considerable interest has focused on the development of new therapies that
      substantially raise levels of HDL-cholesterol. The highly publicized failure of
      the cholesteryl ester transfer protein inhibitor torcetrapib has fuelled
      speculation that raising HDL-cholesterol may not be a viable strategy for the
      development of new therapies. It has also highlighted the complexity of the
      relationship between HDL and protection from cardiovascular disease. Accordingly,
      functionality has become an important factor for consideration in the development
      of new agents that raise HDL-cholesterol. The evidence for the biological
      activity of HDL, and both existing and emerging therapeutic strategies are
      reviewed.

PMID- 18729002
TI  - Pulmonary arterial hypertension: on the way to a manageable disease.
AB  - Pulmonary arterial hypertension (PAH) is an orphan disease for which no specific
      pharmacological therapy was available until 1996. Pharmacotherapy for PAH is
      currently dominated by three endothelin receptor antagonists, bosentan,
      ambrisentan and sitaxentan (which is not yet approved in the US), and the PDE5
      inhibitor sildenafil. Drug candidates undergoing phase III clinical trials for
      PAH include inhalable and oral treprostinil, aviptadil (an inhalable vasoactive
      intestinal peptide), and the PDE5 inhibitor tadalafil. Riociguat, a soluble
      guanylate cyclase stimulator, is scheduled to enter phase III clinical trials in
      2008. By approximately 2010, the role of infusable or injectable PGs as treatment
      for PAH will likely diminish significantly, while inhalable nitric oxide will
      remain as mainstay therapy in neonatal PAH. Benefits in survival and quality-of
      life will decide if any of the more experimental approaches that utilize newly
      discovered molecular pathways in PAH will ultimately result in marketed drugs.

PMID- 18729004
TI  - Endothelial dysfunction and chronic kidney disease: treatment options.
AB  - Endothelial cells detect physical and chemical changes in the blood vessels, and
      release various factors to counter these changes to maintain homeostasis.
      Traditional cardiovascular disease risk factors, such as hypertension,
      dyslipidemia and diabetes, cause endothelial dysfunction characterized by off
      balanced vasodilation/vasoconstriction, increased oxidative stress and
      inflammation, deregulation of thrombosis and fibrinolysis, abnormal smooth muscle
      cell proliferation, and a deficient repair mechanism. Patients with chronic
      kidney disease (CKD) have a much higher risk of cardiovascular disease and
      mortality than the general population. Endothelial dysfunction is commonly
      observed in CKD, likely preceding other cardiovascular complications. Lipid
      lowering agents, such as statins, improve endothelial functions and are effective
      in reducing cardiovascular disease risk in the general population, but have not
      demonstrated comparable efficacy in the CKD patient population. Similarly,
      antidiabetic agents, such as thiazolidinediones, that improve endothelial
      function in the general population are less efficacious than expected in slowing
      disease progression and reducing cardiovascular disease risk in CKD patients.
      Interestingly, agents that activate the vitamin D receptor (VDR) for the
      treatment of hyperparathyroidism secondary to CKD are associated with a survival
      benefit in CKD patients that is likely mediated through the effects of the VDR on
      modulating key components involved in endothelial dysfunction. However, a
      randomized, clinical study is required to confirm the survival benefit of VDR
      activation therapy for CKD patients. Results from clinical studies suggest that
      managing hypertension alone may not be adequate in slowing CKD progression and
      its related cardiovascular complications. Angiotensin-converting enzyme
      inhibitors and angiotensin receptor blockers that target the renin-angiotensin
      system slow CKD progression, possibly due to their effects on improving
      endothelial function, independent of controlling blood pressure.

PMID- 18729003
TI  - Mineralocorticoid receptor antagonists and endothelial function.
AB  - Hyperaldosteronism is associated with endothelial dysfunction and impaired
      vascular reactivity in patients with hypertension or congestive heart failure.
      When present, endothelial dysfunction is an independent predictor of adverse
      cardiovascular events. The mineralocorticoid receptor (MR) antagonists
      spironolactone and eplerenone reduce morbidity and mortality, and it has been
      suggested that this occurs, in part, as a result of improved vascular function.
      The routine use of MR antagonists in patients with cardiovascular disease,
      however, is limited by the development of gynecomastia with spironolactone use
      and hyperkalemia with the use of both agents. Therefore, the development of newer
      agents with more favorable side-effect profiles is needed.

PMID- 18729005
TI  - The effects of growth hormone and insulin-like growth factor-1 on the aging
      cardiovascular system and its progenitor cells.
AB  - Aging is a major risk factor for the development of cardiovascular disease. Aging
      is also associated with a decline in the growth hormone (GH) and insulin-like
      growth factor-1 (IGF-1) axis. This axis impacts endothelial and vascular smooth
      muscle cell biology, as well as cardiac function. The number of endothelial
      progenitor cells (EPCs) also decreases with age and is emerging as a surrogate
      measurement of vascular senescence. Studies suggest that EPCs impact vascular
      health by modulating vascular repair and function. Current evidence demonstrates
      that EPC number and function is restored with a GH-mediated increase in serum IGF
      1. Modulation of the GH and IGF-1 system may therefore provide a useful therapy
      in the prevention of age-associated changes in the cardiovascular system and in
      future regenerative cell-based therapies.

PMID- 18729006
TI  - Glucose-6-phosphate dehydrogenase: a novel therapeutic target in cardiovascular
      diseases.
AB  - Vascular dysfunction associated with diabetes, heart failure and pulmonary
      hypertension is the major cause of morbidity and mortality worldwide. Although
      the causes of vascular dysfunction remain unclear, altered glucose metabolism
      appears to be a common factor in these diseases. For example, in diabetes,
      increased glucose-6-phosphate dehydrogenase (G6PD) activity and elevated NADPH
      levels are associated with endothelial and vascular dysfunction. Also, there is a
      10-fold increase in myocardial G6PD expression and a 2-fold increase in G6PD
      activity in pacing-induced heart failure compared with normal hearts. In
      addition, the inhibition of G6PD ameliorates chronic hypoxic pulmonary
      hypertension. Lastly, G6PD plays a role in mediating angiotensin II-induced
      hypertrophy of smooth muscle and in the development of atherosclerosis. While it
      is understood that G6PD-derived NADPH, which is a cofactor for NADPH oxidase,
      enhances superoxide anion generation and elevates oxidative stress in diabetes,
      heart failure, and angiotensin II-induced hypertrophy of smooth muscle, there are
      no specific drugs available to study the role of G6PD and G6PD-derived NADPH in
      organ function and the development of human diseases. This warrants the
      development of new drugs or genetic approaches to target G6PD for investigational
      and clinical use. This review discusses the specificity and side effects of
      existing investigational G6PD inhibitors.

PMID- 18729008
TI  - Hemospan: a hemoglobin-based oxygen carrier for potential use as a blood
      substitute and for the potential treatment of critical limb ischemia.
AB  - Hemospan, a novel hemoglobin-based oxygen carrier and plasma expander, is being
      developed by Sangart Inc for use as a blood substitute and for the treatment of
      critical limb ischemia. Hemospan is currently undergoing phase III clinical
      trials in Europe and phase II clinical trials in the US for use as a blood
      substitute, and phase II clinical trials in Sweden for critical limb ischemia.

PMID- 18729007
TI  - Induced ion currents and the endothelin pathway as targets for anti-arrhythmic
      agents.
AB  - The development of novel anti-arrhythmic drugs is necessary, specifically agents
      that do not cause torsades de pointes (Tdp). Ion channelopathy that is involved
      in mechanisms underlying sudden cardiac death (SCD) includes both ion channels in
      the membrane, and the calcium-releasing channels and the calcium uptake process
      in the sarcoplasmic reticulum. Advances in the understanding of abnormalities of
      ion channels in the myocardium caused by congenital defects or by a failing heart
      and cardiomyopathy offer further insights into the relationship between
      channelopathy and SCD. Enhanced L-type Ca2+ current (ICa.L) activity has been
      detected in the hearts of patients with a mutation of the Cav1.2 gene; these
      patients exhibit a high risk of SCD. Rats with thyroxin-induced cardiomyopathy
      demonstrate an increase in ICa.L activity that is responsible for exacerbated
      ventricular fibrillation (VF). This is suppressed by propranolol or CPU-86017, a
      class III anti-arrhythmic agent with potent antioxidant activity. Interestingly,
      an increase in rapidly (IKr) and slowly (IKs) activating delayed rectifying K+
      currents is caused by gain-of-function mutations of the KCNH2 and KCNQ1 genes,
      respectively, in patients with short QT syndrome (SQT). Increased IKr and IKs,
      which are associated with exacerbated VF, are also found in models of thyroxin
      induced cardiomyopathy and are suppressed by CPU-86017. ICa.L, IKr and IKs can
      also be induced in cardiomyocytes when incubated with isoproterenol. A reversal
      of upstream lesions by an endothelin receptor antagonist CPU-0213 provides
      suppression of ventricular tachyarrhythmias and upregulates FK506 binding protein
      12.6. CPU-86017 and its chiral isomer SR-CPU-86017 relieve upstream lesions, with
      mild suppression of IKr and moderate suppression of IKs and ICa.L. These agents
      may be promising as anti-arrhythmic agents that produce less Tdp
      tachyarrhythmias.

PMID- 18729009
TI  - Apixaban, an oral, direct inhibitor of activated Factor Xa.
AB  - Apixaban is an oral, direct Factor Xa inhibitor that is being developed by
      Bristol-Myers Squibb Co and Pfizer Inc. Apixaban is currently undergoing phase
      III clinical trials for cerebrovascular ischemia, deep vein thrombosis and lung
      embolism, and phase II clinical trials for coronary artery disease.

PMID- 18729011
TI  - The role of genetic association studies in identifying new drug targets.

PMID- 18729010
TI  - Hematide, a novel peptide-based erythropoiesis-stimulating agent for the
      treatment of anemia.
AB  - Hematide is a synthetic peptide-based erythropoiesis-stimulating agent that is
      being developed by Affymax Inc and Takeda Pharmaceutical Co Ltd. Hematide is
      undergoing phase III clinical trials for anemia.

PMID- 18729012
TI  - Noninvasive imaging of receptor function: signal transduction pathways and
      physiological readouts.
AB  - Intracellular signaling describes the process of information propagation from the
      cell surface to the location within the cell where a biological response is
      executed. Signaling pathways involve a complex network of interacting molecular
      species. It is obvious that information on the activation of individual pathways
      is highly relevant in biomedical research, both from a diagnostic point of view
      and for evaluating therapeutic interventions. Modern molecular imaging approaches
      are capable of providing such information in a temporo-spatially resolved manner.
      Two strategies can be pursued: imaging individual pathway molecules or targeting
      protein-protein interactions, which are key elements of the signaling networks.
      Assays such as fluorescence resonance energy transfer, two-hybrid, protein
      fragment complementation or protein splicing have been adapted to allow studies
      in live mice. The major issues in imaging signal transduction are sensitivity, as
      critical species occur at low concentration, and the fact that the processes
      targeted are intracellular, that is, exogenous probes have to cross the cell
      membrane. Currently, the majority of these imaging methods are based on genetic
      engineering approaches and are therefore confined to experimental studies in
      animals. Exogenous probes for targeting intracellular pathway molecules are being
      developed and may allow translation into the clinic.

PMID- 18729013
TI  - Development of proteasome inhibitors in oncology and autoimmune diseases.
AB  - The proteasome is a multicatalytic protease complex that mediates the controlled
      degradation of intracellular proteins, including key components of pathways that
      contribute to cancer cell growth and immune cell signaling. Validation for the
      proteasome as a therapeutic target in oncology was provided by bortezomib, a
      proteasome inhibitor that was approved for the treatment of multiple myeloma in
      2003. Since that time, a number of structurally and mechanistically distinct
      proteasome inhibitors have entered clinical development in oncology. In this
      review, the chemical properties, preclinical antitumor activities and early
      clinical trials of these next-generation proteasome inhibitors are described and
      the potential for future proteasome inhibitor development in autoimmune
      indications is discussed.

PMID- 18729014
TI  - Treating acute ischemic stroke.
AB  - Acute ischemic stroke (AIS) is a common disorder that has only one associated
      approved therapy: intravenous tissue plasminogen activator (iv t-PA). A limiting
      factor to the use of iv t-PA is that it must be initiated within 3 h of stroke
      onset. Efforts to expand the therapeutic time window are underway and include
      image evaluation of the ischemic penumbra to target those patients who are most
      appropriate for treatment. Intra-arterial t-PA is also used only in some
      treatment centers despite convincing proof of efficacy of this therapy. Devices
      to restore perfusion that have been approved in the US for recanalization exist,
      but these are not approved for use in stroke therapy. Many neuroprotective drugs
      have been evaluated as potential acute stroke therapies, but none have shown
      efficacy, hence the future of neuroprotection as a strategy for acute ischemic
      stroke therapy remains uncertain.

PMID- 18729015
TI  - Ion channels as potential targets for the treatment of depression.
AB  - Major depressive disorder is highly prevalent and remains inadequately treated.
      Numerous studies have demonstrated that modulation of ion channel activity can
      reduce depression-like behavior in animal models or depressive symptoms in
      humans. N-Methyl-D-aspartate and nicotinic acetylcholine receptor blockers have
      demonstrated promise as potential antidepressant agents in humans. Moreover,
      behavioral and physiological findings have provided evidence that the more
      recently characterized ion channel TWIK-related K+ channel-1 is a potential
      antidepressant target; however, drugs directed at this channel have yet to
      undergo clinical testing. Animal studies and genetic association findings also
      suggest that a number of other channel types, including voltage-gated calcium (N
      type), potassium (Kv7), serotonin 5-HT3 and purinergic P2X7 channels, may
      influence depression-like behavior. The therapeutic utility of some ion channels
      will be limited by their role in multiple physiological or pathophysiological
      processes. Nevertheless, a number of strategies are being employed to provide
      improved specificity of action.

PMID- 18729016
TI  - 5-HT6 receptor antagonists: prospects for the treatment of cognitive disorders
      including dementia.
AB  - Several serious neurological and psychiatric disorders are associated with
      cognitive impairment. Thus, drugs targeting the cognitive symptoms of these
      diseases would be expected to provide significant benefits to these patient
      populations. A growing body of preclinical evidence has supported the use of
      serotonin 5-HT6 receptor antagonism as a promising mechanism for treating
      cognitive dysfunction. Following the discovery of a new generation of 5-HT6
      receptor ligands with improved physicochemical properties, leading to superior
      brain penetration, additional support for the 5-HT6 hypothesis has been provided
      by clinical trial data for three molecules in drug development.

PMID- 18729017
TI  - mGluR5 antagonists: discovery, characterization and drug development.
AB  - Disturbances of glutamate-mediated neurotransmission have been implicated in a
      broad range of nervous system disorders. Numerous attempts to correct nervous
      system dysfunction by pharmacological intervention at glutamate receptors have
      been made, and some of the approaches have achieved a high level of preclinical
      validation. However, in a number of cases involving agents acting as blockers of
      the ionotropic glutamate receptors, clinical success could not be achieved,
      mostly because of the lack of a therapeutic window. The identification of the
      metabotropic glutamate receptor (mGluR) family and their modulatory role in the
      control of neurotransmission provided a new means to alter glutamatergic
      transmission. Furthermore, selective agents acting as allosteric antagonists at
      the mGluR5 subtype have demonstrated therapeutic potential. The identification
      and characterization of mGluR5 antagonists and recent progress in clinical
      development are summarized.

PMID- 18729018
TI  - Small-molecule inhibitors of protein-protein interactions.
AB  - Protein-protein interactions regulate almost all aspects of cellular signaling
      and aberrant protein-protein interactions have the potential to cause or
      contribute to human disease. The modulation of these interactions by drug-like
      molecules would offer previously unavailable opportunities to explore the
      relevance of pre-selected protein-protein interactions for cellular signaling, as
      well as benefits to patients. After an initial period of skepticism with regards
      to feasibility, there is now an encouraging set of data indicating that the
      effective and selective modulation of protein-protein interactions by drug-like
      molecules is attainable. This review highlights selected areas of current
      research that are aimed at identifying potent inhibitors of disease-relevant
      protein-protein interactions.

PMID- 18729019
TI  - Antibody therapeutics, antibody engineering, and the merits of protein stability.
AB  - Antibodies are highly soluble, multidomain proteins that are well suited for
      biopharmaceutical development; however, engineering antibodies to perform novel
      activities or to have enhanced clinical utility can have a detrimental effect on
      their biophysical properties. Various innovative designs, such as single-chain
      variable fragments (scFvs) and domain antibodies (dAbs), have been utilized to
      obtain the antigen-binding properties of natural antibodies, while using a
      minimal amount of the polypeptide sequence of an antibody. These designs can be
      used for generating diverse antibody libraries to support discovery and
      optimization and also serve as excellent building blocks for constructing more
      complex protein therapeutics, such as bispecific antibodies. However, engineered
      antibody-like proteins, including scFvs, are often unstable and prone to
      aggregation, compromising both protein production and quality. Research over the
      past few years has enhanced our understanding of how interdomain interactions
      within antibodies contribute to protein stability. This knowledge and sustained
      research to develop methods for modifying antibody fragments to improve stability
      have begun to have a positive impact on the quality of antibody libraries for
      discovery purposes and the viability of highly engineered proteins, such as
      bispecific antibodies, as therapeutics.

PMID- 18729020
TI  - DUBs and disease: activity assays for inhibitor development.
AB  - Deubiquitinating enzymes (DUBs) cleave ubiquitin from substrate proteins and so
      influence the biochemical properties of these proteins, such as their half-life,
      by a reduction in proteasomal degradation. Several DUBs have been demonstrated to
      deubiquitinate oncogenic proteins and tumor suppressors, and their activities
      have been implicated in numerous processes related to disease, including cancer
      and neurodegeneration. The importance of various DUBs is well established, but
      the understanding of both their selectivity and reactivity in the ubiquitin
      proteasome system is comparatively poor. In this review, the published methods
      that are available to study DUB action in vitro and their application in finding
      inhibitors are discussed.

PMID- 18729021
TI  - Unraveling the details of prion (con)formation(s): recent advances by mass
      spectrometry.
AB  - Transmissible spongiform encephalopathies (TSEs), or prion diseases, are
      neurodegenerative disorders affecting both humans and animals. TSEs are caused by
      the infectious agent 'prion', which is poorly characterized and is believed to be
      composed of the pathological isoform--TSE-associated prion protein (PrP(TSE))--of
      a physiological, host-encoded protein called cellular prion protein (PrPC).
      Whereas it is certain that the process of PrP(TSE) formation has a fundamental
      role in the development of TSE, other aspects, including the mechanism of this
      process, the nature and the role of the factors involved (related or unrelated to
      PrP), and the relationship between PrP(TSE) conformations and disease phenotypes
      remain poorly defined. Different proteomic strategies have been utilized to
      address these issues. In this ambit, mass spectrometry (MS) has gained a
      prominent position, with applications that range from the investigation of the
      molecular pathogenesis to the development of new diagnostic tools. The aim of
      this review is to outline these advances and to highlight promising avenues to
      prion research that have been opened by novel MS applications.

PMID- 18729022
TI  - Use of fluorescent imaging to investigate pathological protease activity.
AB  - Proteases play pivotal roles in the normal function of cells. In addition, the
      expression and activity of proteases are significantly upregulated in several
      pathologies, including cancer, arthritis and atherosclerosis, and hence they can
      be considered to be biological markers for these pathologies. The hydrolyzing
      activity of proteases has been used to generate a variety of fluorescent imaging
      reagents, the design and utility of which are reviewed here. The use of imaging
      reagents to visualize protease activity allows for improved detection of various
      pathologies as well as the ability to monitor the efficacy of therapies in vivo
      and provide molecular information regarding the nature of the pathology.

PMID- 18729023
TI  - Positron emission tomography for modeling pathophysiological processes in vivo.
AB  - Positron emission tomography (PET) is a powerful tool for imaging and quantifying
      (patho)physiological processes in the human body. PET has been successfully used
      for staging diseases and evaluating response to treatment. Furthermore, PET may
      contribute to drug development and individualized treatment planning. This
      article reviews the use of several PET tracers in drug development and their
      clinical application in the fields of neurology, oncology and cardiology.

PMID- 18729024
TI  - [Continuing Medical Education (CME)].

PMID- 18729025
TI  - [Job insecurity as risk for adverse health effects amongst german workers: a
      cohort study].
AB  - OBJECTIVE: This study investigates the relation of perceived job insecurity and
      self-rated health amongst German workers. METHODOLOGY: The database of the
      investigation was created from survey data of the Socio-economic Panel (SOEP).
      The analysis considered data from the surveys in 2003, 2004 and 2006. Included
      were all employed persons aged 30-60 years in 2003 (n=9 272). In order to analyse
      the impact of perceived job insecurity measured in 2003 on the self-rated health
      in 2004 (n=8 709) and 2006 (n=7 773) an ordinal logit-model was used. RESULTS:
      Persons with high job insecurity had--after adjustment for age, gender, education
      and occupational status--a higher risk of adverse self-rated health both after
      one year (OR=1.18; 95% CI: 1.06-1.31) and three years (OR=1.18; 95% CI: 1.05
      1.32). The analysis could also identify an interaction between occupational
      status and job insecurity. High job insecurity proved to be a health risk,
      particularly for persons with lower occupational status (2004: OR=1.37; 95% CI:
      1.15-1.62; 2006: OR=1.31; 95% CI: 1.09-1.57). CONCLUSION: The study supports the
      proposal that, for a cohort of German workers, perceived job insecurity increases
      the risk of adverse health effects amongst workers with lower occupational
      status.

PMID- 18729026
TI  - [Indebtedness and mortality: analysis at county and city levels in Germany].
AB  - INTRODUCTION: Little is known about the influence of individual debts on health
      inequalities in Germany. Studies from English-language countries have shown that
      indebtedness is a great burden in every-day life that leads to mental stress and
      is related to negative health outcomes. Our paper, for the first time, analyses
      the role of indebtedness on mortality in Germany. METHODS: Using ecological level
      data of Germany's 439 administrative districts, we assessed the role of
      unemployment, income, educational level, population density, regional prosperity,
      number of hospital beds and of the independent effect of indebtedness on
      mortality. The variance explained by indebtedness was determined by means of
      multiple linear regression models. Data were provided by the Federal Statistical
      Office of Germany and Schufa Holding AG. RESULTS: Indebtedness and unemployment
      are moderately correlated. Even so, a significant independent effect of
      indebtedness on mortality can be shown. Indebtedness contributes to the
      explanation of health inequalities and, together with other socioeconomic factors
      and the federal state, explains 59% of the variance in age-standardised district
      level mortality. Indebtedness explains 6% of variance. CONCLUSION: For the first
      time in Germany, this study shows that indebtedness not only influences
      population health as a result of low income or unemployment but also has an
      independent, albeit rather small, effect. Studies focussing on social inequity
      and health should further examine the role of indebtedness and also include an
      analysis on the individual level.

PMID- 18729027
TI  - [Cancer screening for women is less frequently visited in regions with lower
      household income--analysis of data from health insurances in Bavaria].
AB  - AIM OF THE STUDY: Differences in health care in Germany have rarely been
      analysed. Recent research, however, indicates that subjects of the lower social
      class participate in cancer screening less frequently. METHODS: Participation in
      screening for cervical cancer among women older than 20 years has been analysed
      using billing information of the KVB (Kassenarztlichen Vereinigung Bayern) for
      the period from 2002-2005. Women were assigned to one of the 96 Bavarian
      districts based on their postal code. The following variables were used:
      Participation rate in cervical cancer screening; age; average household income;
      gynaecologists per 10,000 women. Multivariate analyses were based on age
      stratified linear regressions. RESULTS: There are considerable regional
      differences in participation in screening for cancer among older women.
      Participation rates are lower in districts with lower average household income.
      The correlation between participation rates and average household income shows an
      almost linear dependence on the level of districts. This association could not be
      explained by the variable "gynaecologists per 10,000 women". CONCLUSION: In order
      to provide social equality in health care, regional differences in cancer
      screening participation should be targeted. This is especially important in
      districts with lower average household incomes.

PMID- 18729028
TI  - [Overall burden to society caused by hyperkinetic syndrome (HKS) and attention
      deficit hyperactivity disorder (ADHD)].
AB  - OBJECTIVE: The purpose of this work was to provide an analysis of medical costs
      for HKS/ADHD on the basis of a cost-of-illness study. METHODS: A systematic
      literature review concerning the direct and indirect costs of HKS/ADHD and its
      related implications was complemented by a special analysis of the German Federal
      Office of Statistics on ICD-10 F 90. RESULTS: An analysis of overall medical
      costs by the Federal Office of Statistics results in expenses of 142 million euro
      in 2002 corresponding to ca. 630 euro per patient per year. These values are
      considerably below the values calculated for the USA. Increased indirect costs
      related to different implications of the indication were stated in international
      studies. CONCLUSION: A first estimate of the direct costs for HKS/ADHS in Germany
      has been conducted. A reduction of the difference between the German and the US
      direct cost values may be expected. An increased level of the indirect costs
      related to HKS/ADHD may be assumed for Germany and requires further research.

PMID- 18729029
TI  - [Evaluation of a pilot study on measles vaccination in Bavarian preschool
      children].
AB  - Several areas of Bavaria show measles vaccination coverage in preschool children
      below 95%. Repeated outbreaks could be attributed to this situation. A
      recollection model in nurseries was tested in order to document the vaccination
      rate in this age group and to measure the percentage of vaccinations due to
      intervention. Parents of new entrants to nurseries in a randomly selected rural
      district were asked to provide measles vaccination records of their kids and to
      fill in a questionnaire. 121 out of 144 vaccination records (85%) documented a
      complete immunisation status for measles. 12 children had not been vaccinated
      against measles, 10 children had received one vaccination. Eight out of these 22
      children obtained supplementary measles immunisation at the time of
      ascertainment. The results provided are of limited statistical significance due
      to the small sample size. Further intervention studies have to be conducted and
      should even include measures supported by legal regulations.

PMID- 18729030
TI  - [Current vaccination status of health-care personnel in Brandenburg, Saxony And
      Saxony-Anhalt].
AB  - OBJECTIVE AND METHODS: A complete vaccination status against infectious diseases
      is important for protecting health care professionals as well as patients. A
      survey based on a written questionnaire was conducted to record the actual
      vaccination status against diphtheria, hepatitis A und B, mumps, measles,
      poliomyelitis, rubella and tetanus. 642 general practitioners (family physicians
      and surgeons), 298 medical students and 962 nursing students from areas of
      eastern Germany completed the questionnaire. RESULTS AND CONCLUSIONS: There was
      no complete vaccination status against those diseases covered by the survey.
      Physicians had a good immunisation rate against tetanus (96.2%) and diphtheria
      (91.8%). The number of physicians without immunisation against measles (42.9%),
      HA (29.3%) and HB (12.7%) was unsatisfactory. Less than 50% of nursing students
      and medical students could show a complete vaccination status against MMR. In
      both student groups there were also gaps for vaccines against tetanus,
      diphtheria, HA and HB. Complete vaccination status was found to be in the range
      of 74-81% for tetanus, 51-66% for diphtheria, 47-63% for HA and 62-73% for HB.
      Furthermore, there is a need for actions to raise the immunisation rates and for
      improving the health protection for all persons involved (professionals and
      patients) in the health care system.

PMID- 18729031
TI  - [What can public health departments do to improve hand hygiene in hospitals?].
AB  - BACKGROUND: Compliance with hand hygiene in hospitals often needs improvement.
      Public health departments should support the hospitals in implementing good hand
      hygiene. This may be achieved by assessing the consumption of hand disinfectant
      and discussing the results with the hospitals. MATERIAL AND METHODS: In the
      course of routine infection control visits, the Frankfurt public health
      department asked for the data on the consumption of hand disinfectant in the
      hospitals. In 2004, overall consumption of the hospitals was asked for, in 2005
      consumption in all parts (wards, operating units, endoscopy units, ambulances
      etc.) was obtained, completed by the data of patients per day and ward in 2006 in
      some of the hospitals. RESULTS: As expected, larger hospitals exhibited higher
      overall hand disinfectant consumption. With respect to the number of hospital
      beds available, the differences were no longer significant. In the various
      hospitals, 27-64% of the overall amount of hand disinfection was used in wards,
      17-57% in operative units, and 3-20% in other areas. Assessment of disinfection
      consumption in 120 wards, covering 709 339 patient days, resulted in great
      differences between intensive care units (median 97 ml/patient and day) and non
      intensive units (adults 18 ml/patient day, children 41 ml/patient day).
      DISCUSSION: Controlling data on the consumption of hand disinfectant is easily
      possible. By demanding and discussing these data in the course of their routine
      hygiene control visits, the public health departments should emphasise the
      importance of hand hygiene as an effective method for preventing nosocomial
      infections. In addition, the hospitals should be encouraged to take part in the
      "Clean Hands Action", the German branch of the WHO campaign "Clean care is safer
      care".

PMID- 18729032
TI  - [Methodological basis for evidence-based medicine].

PMID- 18729034
TI  - [Progesteron--an old--new option in the prevention of preterm birth].

PMID- 18729035
TI  - [Three-dimensional scatter plot analysis to estimate the risk of foetal
      aneuloidy].
AB  - PURPOSE: First trimester screening (FTS) according to Nicolaides is now a
      worldwide established method for prenatal aneuloidy screening. An improvement was
      achieved by the "Advanced First Trimester Screening" (AFS). It was the aim of the
      current study to set up scatter plots from nuchal translucency (NT), Papp-A and
      fbeta-hCG, to derive likelihood ratios therefrom and to apply them to a test
      collective. We wanted to examine whether or nor the test performance of FTS could
      further be improved. MATERIAL AND METHODS: In a multicentre study 10 136
      singleton pregnancies were recruited. Risk assessment for the presence of
      aneuploidies was performed by the Pia Fetal Database (PIA). In addition, all data
      were recalculated by the AFS module of the online platform www.firsttrimester.net
      . In a third step, a newly developed algorithm was utilised, in which the foetal
      parameters DeltaNT, Papp-A and fbeta-hCG were put into a three-dimensional
      scatter plot. The surrounding volume was segmentally divided and for each space
      the relation of the healthy to the affected foetuses found therein was
      determined. Furthermore, for all participiants of this study, the likelihood
      ratios were examinied at the segment according to the currently measured values.
      This method is designated as AFS-3D. RESULTS: Within the observed fetuses, 86
      cases with aneuploidy were detected. By appropriate choice of the cut-off the
      sensitivities were found to be 83 % (PIA and AFS) and 82 % (AFS-3D),
      respectively, and do not differ significantly from each other. The specificity
      could be improved from 94 % (PIA) to 96 % (AFS) and was further advanced to 98 %
      by the AFS-3D method. At the same time the false positive rate was lowered from
      654 (PIA) to 397 (AFS) and 228 (AFS-3D) cases, respectively. DISCUSSION: By means
      of the new AFS-3D method the same count of diseased fetuses was detected compared
      with prior screening tests. Simultaneously, expectant mothers were spared from
      unnecessary invasive diagnostics in 65 % of the cases. The choice of an altered
      cut-off or other volume shapes are feasible and should be examined in further
      studies.

PMID- 18729036
TI  - Outcome measures in perinatal medicine - pH or BE. The thresholds of these
      parameters in term infants.
AB  - BACKGROUND: Hypoxia and severe foetal acidosis may lead to cerebral injuries and
      multi-organ failure. Base excess (BE) and actual pH determined in umbilical
      artery (UA) blood are valid parameters to measure (metabolic) acidosis. Until now
      there is no consensus worldwide as to which of the two parameters should
      preferably be used and which thresholds should be applied: the thresholds 7.000,
      7.100 and 7.200 are discussed for pH,UA and - 16.0 mmol/l for BE,UA,
      respectively. The aim of this study was to redefine these thresholds for term
      infants taking into account the entire spectrum of complications in early
      neonatal life and to compare the diagnostic power of both variables under
      investigation. METHODS: 512 foetuses all with a pH,UA < 7.100 were enrolled in
      this retrospective study. In this paper only term infants (n = 398) without major
      malformations were analysed. In order to quantify foetal morbidity and mortality
      an asphyxia complication (AC) score was designed using the Apgar score after 1
      min and all possible complications encountered in the neonate until discharge
      (mainly from the NICU). Routine acid-base (AB) measurements (Radiometer,
      Copenhagen) were available (UA and UV blood) in nearly all cases. In this
      context, BE was corrected to 100 % oxygen-saturation (BE (oxy.)) using the
      (calculated) actual saturation (BE (act.oxy.)) of haemoglobin in each case
      because sO2 (%) becomes very low in severe acidosis. Oxygen saturation (%) was
      determined according to Ruiz et al. using haemoglobin F. Matched pairs (pH,UA >
      7.10) were defined using the variables (i) gestational age, (ii) birth weight (+/
      100 g), (iii) sex, and (iv) parity. RESULTS: Analysing term infants with a
      definitely good outcome (n = 389) led to the following AB variables in UA blood:
      10 % had a pH < 7.000; the lowest pH was 6.717, the highest pCO2 was 118 mmHg and
      the lowest BE(oxy.) amounted to - 32.4 mmol / l. 90 % of these neonates had an
      oxygen saturation that was still > 3.0 %. However, early neonatal morbidity due
      to hypoxia and acidosis was remarkable; therefore these AB variables could not
      serve as thresholds. Relying on clinical criteria, no acidotic morbidity was
      accepted, except for respiration disorders in early neonatal live (C score)
      together with Apgar scores down to 4 after one minute. This led to an AC score of
      < or = 8 (n = 378). In this group the lowest pH,UA was 6.890 and BE(oxy.) was -
      25.1 mmol / l, respectively. In order to have a "buffer zone" of 10 % in each
      variable distribution (10 (th) / 90 (th) percentile). the following thresholds
      could be evaluated in UA blood: pH: 7.000, pCO2: 84 mmHg, sO2: 3.0 % and BE(oxy.)
      - 20.0 mmol/l. Only 13 (matched) neonates suffered from an AC score > 8 and had
      all pH values > or = 7.100 (3.3 % overlap). These foetuses seemed to be not at
      risk concerning injuries and severe complications. In UA blood the actual pH
      always offers closer correlations with the AC score when compared with the BE
      (oxy.) value. CONCLUSION: Thresholds in UA blood for pH, pCO2, sO2 and BE(oxy.)
      in term-infants are: 7.000, 84 mmHg, 3.0 % and - 20 mmol/l, respectively.
      Delivery of an otherwise healthy baby without getting in touch with these
      thresholds seems to be safe both for the baby and the obstetrician. In addition,
      severe neonatal depression (Apgar 1 min: 0 and 1) is usually avoided (0 / 398).
      BE(oxy.) does not offer a higher diagnostic power when compared with actual pH.

PMID- 18729037
TI  - [Paradigm shift in obsterics--the example of induction of labour].
AB  - Paradigm shift is moulded by the rapid advances in scientific knowledge, the
      results of evidence-based medicine and the guidelines and recommendations
      resulting therefrom as well as the continuous changes in medicine's social
      cultural ambient. Features of a complex medical and social development are the
      declining number of births, a significant increase in the frequency of caesarean
      sections and an almost two-fold elevation of the number of induced births. This
      is especially valid for an overproportional rise in elective induction of labour
      which, today, represents the most frequently indicated intervention in
      obstetrics. The elective induction of labour in nulliparous women, however, is
      associated with an almost two-fold higher incidence of caesarean sections. It is
      clear for the example of induction of labour that today more than ever obstetric
      interventions are subject to a broad spectrum of paramedical as well as medical
      factors and are in fact influenced by them. These include, above all, the
      pregnant woman's right of self-determination and her individual needs, the
      logistics and infrastructure of the hospital, the concern about medico-legal
      disputes, and the increasing economic pressure. In this context the ever
      increasing competitive situation among the obstetric clinics plays a decisive
      role. Prerequisite for the induction of labour is an individual risk-use analysis
      that should be clearly and thoroughly explained to the patient and her partner in
      a personal conversation. The pregnant woman's frustration about a prolonged
      course of labour is a complication of the induction that must not be
      underestimated and leads more often than in the past to a secondary caesarean
      section. Recent publications warn of an increased maternal morbidity and
      perinatal mortality in cases of an induction of labour following a previous
      caesarean section. In contrast to the caesarean saving programme propagated in
      the 1990s, the historical postulate "once a caesarean always a caesarean" is
      experiencing an obvious renaissance. Irrespective of the non-medical and medical
      influencing factors, the obstetrician should not forget his / her own experience
      and intuition or confidence in his/her own abilities and pass obstetrics on to
      future generations as an individual art.

PMID- 18729038
TI  - [Mental models and the quality of medical decisions].

PMID- 18729039
TI  - The dual actions of Paederia scandens extract as a hypouricemic agent: xanthine
      oxidase inhibitory activity and uricosuric effect.
AB  - Hyperuricemia is associated with a number of pathological conditions, such as
      gout. Lowering of elevated uric acid levels in the blood could be achieved by
      xanthine oxidase inhibitors and inhibitors of renal urate reabsorption. Some
      natural compounds isolated from herbs used in traditional Chinese medicine have
      been previously demonstrated to act as xanthine oxidase inhibitors. In the
      present investigation, Paederia scandens (Lour.) Merrill (Rubiaceae) extract
      (PSE; 4.5, 2.25, and 1.125 g/kg) orally for 14 days was demonstrated to possess
      in vivo potent hypouricemic activity in hyperuricemic rats pretreated with
      potassium oxonate. In addition, PSE was also demonstrated to be an inhibitor of
      xanthine oxidase. Lineweaver-Burk analysis of the enzyme kinetics indicated that
      the inhibition of PSE was of a mixed type. Using an oxonate-induced hyperuricemic
      rat model, PSE was indeed shown to exhibit uricosuric action in vivo, which could
      explain, at least in part, the observed hypouricemic effect of PSE in these rats.
      The potential application of this compound in the treatment of conditions
      associated with hyperuricemia is discussed.

PMID- 18729040
TI  - Thyme extract, but not thymol, inhibits endothelin-induced contractions of
      isolated rat trachea.
AB  - Thyme extract is known to posses spasmolytic effects on isolated trachea and to
      increase ciliary activity. A small part of this effect is mediated via beta (2)
      receptors, but other receptors are supposed to be involved. Endothelin has a
      pathophysiological impact in asthma with respect to hyper-reagibility and
      contracting isolated trachea smooth muscles and was, therefore, investigated.
      Thyme extract inhibited endothelin-induced contraction. Emax decreased depending
      on the concentration of thyme extract indicating a non-competitive inhibition.
      Bosentan, an endothelin receptor antagonist (positive control), acted as a
      competitive inhibitor. The interaction/combination of thyme extract and bosentan
      was additive but not supra-additive indicating an interaction with the endothelin
      system. Thymol (one of the major compounds of thyme extract) did not interact
      with the endothelin system. It is concluded that thyme extract may help in
      diseases related to endothelin hyper-reagibility of the bronchus system such as
      asthma and COPD (chronic obstructive pulmonary disease), although thymol is not
      involved in this effect.

PMID- 18729041
TI  - Antifungal saponins from Paris polyphylla Smith.
AB  - Three steroidal saponins, including one new and two known compounds, were
      isolated from the rhizomes of Paris polyphylla Smith. One- and two-dimensional
      NMR, LC-MS, and interpretation of hydrolytic cleavage experiments led to the
      identification of the structure of the new saponin as ( 25R)-spirost-5-ene-3
      beta,17 alpha-diol (pennogenin) 3- O-{ O- alpha- L-rhamnopyranosyl-(1-->2)- O-[ O
      beta-xylopyranosyl-(1-->5)- alpha- L-arabinofuranosyl-(1-->4)]- beta- D
      glucopyranoside}. The isolated saponins were evaluated for their antifungal
      activity against Cladosporium cladosporioides and Candida species and showed
      comparable activity to chemicals used in some commercial products.

PMID- 18729042
TI  - Induction of NAD(P)H: quinone reductase by rutaecarpine isolated from the fruits
      of Evodia rutaecarpa in the murine hepatic Hepa-1c1c7 cell line.
AB  - Rutaecarpine is a quinazolinocarboline alkaloid isolated from Evodia rutaecarpa
      (Juss.), which has been used in traditional Chinese medicine. The bioactivity
      guided fractionation has led to the isolation of rutaecarpine from the extract of
      the fruits of E. rutaecarpa as the major component possessing NAD(P)H:quinone
      reductase (QR) activity. The activator protein-1 (AP-1), a transcriptional
      factor, in the antioxidant response element (ARE) region plays an important role
      in mediating induction of the target genes by xenobiotics, including
      chemopreventive agents. The present study demonstrates that rutaecarpine induces
      QR activity and gene expression by transactivation of AP-1. To study the
      induction of QR activity and AP-1-mediated QR gene expression by rutaecarpine, we
      performed enzyme and reporter gene assays. This compound markedly induced the
      enzyme activity and mRNA expression levels of QR in a dose-dependent manner.
      Using the luciferase reporter gene assay, a dose-dependent transactivation of AP
      1-mediated luciferase expression was observed upon treatment of rutaecarpine.
      These results suggest that rutaecarpine induces QR gene expression and activity
      through an increase in AP-1 activation.

PMID- 18729043
TI  - Cytotoxic activity of C-geranyl compounds from Paulownia tomentosa fruits.
AB  - The newly discovered 5,7-dihydroxy-6-geranylchromone ( 1) was isolated from
      PAULOWNIA TOMENTOSA fruit and subsequently characterized. The structure of the
      isolated compound was elucidated on the basis of extensive NMR experiments
      including HMQC, HMBC, COSY, and NOESY, as well as HR-MS, IR, and UV. The
      cytotoxicity of 1 was evaluated using a plant cell model represented by tobacco
      BY-2 cells. The other phytoconstituents ( 2 - 8) previously isolated from P.
      TOMENTOSA were similarly evaluated together with the known flavanones 10 and 11.
      The cytotoxicity (human erythro-leukaemia cell line K562) and activity on
      erythroid differentiation of compounds 2 - 9 and 12 and 13 have also been
      evaluated. Acteoside ( 2) was determined to be the most toxic of the compounds
      tested on BY-2 cells, diplacone ( 6) on the K562 cell line. Some aspects of the
      relationship between the flavanone skeleton substitution and the metabolic
      activation necessary for a toxic effect are discussed.

PMID- 18729044
TI  - Angle-distance image matching techniques for protein structure comparison.
AB  - Proteins that contain similar structural elements often have analogous functions
      regardless of the degree of sequence similarity or structure connectivity in
      space. In general, protein structure comparison (PSC) provides a straightforward
      methodology for biologists to determine critical aspects of structure and
      function. Here, we developed a novel PSC technique based on angle-distance image
      (A-D image) transformation and matching, which is independent of sequence
      similarity and connectivity of secondary structure elements (SSEs). An A-D image
      is constructed by utilizing protein secondary structure information. According to
      various types of SSEs, the mutual SSE pairs of the query protein are classified
      into three different types of sub-images. Subsequently, corresponding sub-images
      between query and target protein structures are compared using modified cross
      correlation approaches to identify the similarity of various patterns. Structural
      relationships among proteins are displayed by hierarchical clustering trees,
      which facilitate the establishment of the evolutionary relationships between
      structure and function of various proteins.Four standard testing datasets and one
      newly created dataset were used to evaluate the proposed method. The results
      demonstrate that proteins from these five datasets can be categorized in
      conformity with their spatial distribution of SSEs. Moreover, for proteins with
      low sequence identity that share high structure similarity, the proposed
      algorithms are an efficient and effective method for structural comparison.

PMID- 18729045
TI  - The reduction of starch accumulation in transgenic sugarcane cell suspension
      culture lines.
AB  - Starch only occurs in small amounts in sugarcane, but is, nevertheless an
      unwanted product because it reduces the amount of sucrose that can be
      crystallized from molasses. In an attempt to reduce the starch content of
      sugarcane, the activities of ADP-glucose pyrophosphorylase (AGPase) and beta
      amylase were manipulated using transgenic approaches. Transformation vectors to
      reduce AGPase activity and to increase plastidial beta-amylase activity were
      constructed and used for the transformation of sugarcane calli. The results of
      the manipulations were analyzed in suspension cultures. AGPase activity was
      reduced down to between 14 and 54% of the wild-type control. This led to a
      reduction in starch concentration down to 38% of the levels of the wild-type
      control. beta-Amylase activity was increased in the transgenic lines by 1.5-2
      times that of the wild-type control. This increase in activity led to a reduction
      in starch amounts by 90% compared to wild-type control cells. In both
      experiments, the changes in starch concentrations could be correlated with the
      change in enzyme activity. There were no significant effects on sucrose
      concentrations in either experiment, indicating that these approaches might be
      useful to engineer regenerated sugarcane for optimized sucrose production.

PMID- 18729046
TI  - A vector system for genomic FLAG epitope-tagging in Schizosaccharomyces pombe.
AB  - The fission yeast Schizosaccharomyces pombe is a popular model organism to study
      various cellular processes, although research tools available for S. pombe are
      relatively inadequate. To facilitate genetic and biochemical investigation in S.
      pombe, we report here a system of vectors for genomic FLAG epitope-tagging. These
      vectors enable us to amplify gene-targeting fragments for integration into
      specific loci of the S. pombe genome. All vectors in this report were designed to
      express FLAG epitope-tagged proteins from their endogenous genomic loci. Vectors
      for N-terminal FLAG epitope-tagging allow us to control protein expression levels
      using the wild-type nmt1 promoter, its weaker derivatives, and the urg1 promoter.
      These vectors are available with various antibiotic markers including kanMX6,
      hphMX6, natMX6 and bleMX6, and the his3(+) marker. Vectors for C-terminal FLAG
      epitope-tagging were designed to express FLAG-fusion proteins under the control
      of their native promoters at their own genomic loci, allowing us to characterize
      protein functions under physiological conditions. These vectors are available
      with kanMX6, hphMX6, nat-MX6 and bleMX6 markers. The series of vectors described
      in this report should prove useful for protein studies in fission yeast.

PMID- 18729047
TI  - Isolation and visualization of mouse placental hematopoietic stem cells.
AB  - This unit describes the isolation of hematopoietic stem cells (HSCs) from the
      mouse placenta. The placenta was recently identified as an important
      hematopoietic site that generates HSCs de novo and provides a transitory niche
      for a large pool of HSCs during midgestation. This protocol includes a dissection
      technique for murine placenta, the mechanical and enzymatic steps of placental
      tissue dissociation, and phenotypical identification and isolation of HSCs. It
      also contains a method for immunohistochemical analysis of placenta tissue
      sections to visualize developing HSCs in the placenta.

PMID- 18729048
TI  - Generation of cultured oligodendrocyte progenitor cells from rat neonatal brains.
AB  - The oligodendrocyte progenitor cell (OPC) is one of the most studied progenitor
      cells of the body. It has been extensively researched in tissue culture and more
      recently in vivo using a wide range of markers that recognize transcription
      factors and cell surface markers and identify its earliest development from
      neural stem cells onward. Isolation of OPCs in large numbers and in purified
      preparations has been sought after as a source of cells for the repair of human
      myelin disorders. It has been proposed that such cells could be used as an
      exogenous source of cells for the treatment of lesions in multiple sclerosis and
      the less common genetic myelin disorders such as Pelizaeus-Merzbacher disease.
      Prior to clinical trials, such approaches can be tested in animal models. Here,
      we describe the isolation of rat OPCs in culture conditions that provide large
      numbers of purified populations of cells.

PMID- 18729049
TI  - Sample preparation and in-solution protease digestion of proteins for
      chromatography-based proteomic analysis.
AB  - The adoption of chromatography-based proteomics approaches has resulted in the
      development of new methods for optimal use of these technologies. One such
      technology, named multidimensional protein identification technology (MudPIT),
      directly couples liquid chromatography with tandem mass spectrometry. In the
      MudPIT approach, digested protein samples are directly loaded onto a
      microcapillary column packed sequentially with reversed-phase and strong cation
      exchange resins. Once digested protein samples are loaded onto the column, the
      column is placed in-line between a high-performance liquid chromatography system
      and an electrospray ionization tandem mass spectrometer (ESI-MS/MS). The digested
      protein samples for MudPIT analysis must be directly compatible with ESI-MS/MS,
      so the sample preparation and digestion protocols must be optimized for this
      purpose. The primary objective of all of the protocols in this unit is to yield a
      final digested protein mixture of less than 300 microl that can then be directly
      loaded onto a MudPIT column.

PMID- 18729050
TI  - The use of detergents to purify membrane proteins.
AB  - Extraction of membrane proteins from biological membranes is usually accomplished
      with the help of detergents. This unit describes the use of detergents to
      solubilize and purify membrane proteins. The chemical and physical properties of
      the different classes of detergents typically used with biological samples are
      discussed. A separate section addresses the compatibility of detergents with
      applications downstream of the membrane protein purification process, such as
      optical spectroscopy, mass spectrometry, protein crystallography, or biomolecular
      NMR. Protocols in this unit include the isolation and solubilization of
      biological membranes, phase separation, and support protocols for detergent
      removal and detergent exchange using different methods.

PMID- 18729051
TI  - Determination of membrane protein molecular weight using sedimentation
      equilibrium analytical ultracentrifugation.
AB  - Both the stoichiometry and stability of native membrane protein complexes pose
      challenges to understanding the biology of these proteins. Sedimentation
      equilibrium analytical ultracentrifugation is well recognized as a
      thermodynamically rigorous technique for determining these quantities for
      macromolecules. This unit describes the experimental strategies that can be used
      to extract this information for membrane proteins reconstituted in vitro in
      detergent micelle or detergent/lipid mixed micelle solutions.

PMID- 18729052
TI  - Preparing for biofilm studies in the field.
AB  - In their natural environments, microorganisms are under constant environmental
      selection to form biofilms. Using aquatic biofilms as an example, this unit
      illustrates general concepts in field biology and practical suggestions for
      designing, conducting, and analyzing biofilm experiments at varying distances
      from the laboratory. The unit also addresses an example of a special situation
      (space flight) where experimentation must be done by proxy through another
      individual or machine.

PMID- 18729053
TI  - Biological sand filters: low-cost bioremediation technique for production of
      clean drinking water.
AB  - Approximately 1.1 billion people in rural and peri-urban communities of
      developing countries do not have access to safe drinking water. The mortality
      from diarrheal-related diseases amounts to approximately 2.2 million people each
      year from the consumption of unsafe water. Most of them are children under 5
      years of age-250 deaths an hour from microbiologically contaminated water. There
      is conclusive evidence that one low-cost household bioremediation intervention,
      biological sand filters, are capable of dramatically improving the
      microbiological quality of drinking water. This unit will describe this
      relatively new and proven bioremediation technology's ability to empower at-risk
      populations to use naturally occurring biology and readily available materials as
      a sustainable way to achieve the health benefits of safe drinking water.

PMID- 18729054
TI  - Aphid transmission of plant viruses.
AB  - A majority of plant viruses are transmitted between hosts by insect vectors, and
      it is often important to use insect transmission in the laboratory to maintain
      virus isolates or to study virus-vector-plant interactions. Although many of
      these viruses can also be mechanically transmitted in the laboratory using
      infected sap, maintenance by mechanical transmission can often lead to changes in
      the virus, either minor changes in gene sequences or, in some cases, major
      deletions of genome sequences. These can affect both virus-vector and virus-host
      interactions. This unit describes some simple and practical methods for
      conducting virus transmission experiments using sap-sucking insects.

PMID- 18729055
TI  - Identification of viroids by gel electrophoresis.
AB  - Two-dimensional PAGE involving an initial fractionation under nondenaturing
      conditions followed by a second electrophoresis under denaturing conditions
      provides a powerful means to detect viroids and other small circular RNAs. This
      unit describes a method known as "R(eturn) PAGE" in which denaturation is
      achieved by simultaneously raising the temperature and lowering the ionic
      strength during the second electrophoresis. Under denaturing conditions, circular
      RNAs migrate more slowly than their corresponding linear forms. Following
      fractionation, RNAs are visualized by staining with ethidium bromide, SYBR Gold,
      or silver nitrate. Unlike nucleic acid hybridization or RT-PCR, viroid
      identification by R-PAGE requires no nucleotide sequence information.

PMID- 18729056
TI  - Total internal reflection fluorescence (TIRF) microscopy.
AB  - Total internal reflection fluorescence (TIRF) microscopy represents a method of
      exciting and visualizing fluorophores present in the near-membrane region of live
      or fixed cells grown on coverslips. TIRF microscopy is based on the total
      internal reflection phenomenon that occurs when light passes from a high
      refractive medium (e.g., glass) into a low-refractive medium (e.g., cell, water).
      The evanescent field produced by total internally reflected light excites the
      fluorescent molecules at the cell-substrate interface and is accompanied by
      minimal exposure of the remaining cell volume. This technique provides high
      contrast fluorescence images, with very low background and virtually no out-of
      focus light, ideal for visualization and spectroscopy of single-molecule
      fluorescence near a surface. This unit presents, in a concise manner, the
      principle of operation, instrument diversity, and TIRF microscopy applications
      for the study of biological samples.

PMID- 18729057
TI  - Laboratory maintenance of Bartonella quintana.
AB  - Trench fever is the common name for the acute febrile syndrome associated with a
      Bartonella quintana bacterial infection. The focus of this unit is to describe
      reliable methods for cultivation and cryopreservation of B. quintana and can be
      applied to cultivation and preservation of all Bartonella. Detailed recipes for
      preparation of three types of semisolid media are also included.

PMID- 18729058
TI  - Growth and laboratory maintenance of Campylobacter jejuni.
AB  - Campylobacter jejuni is a fastidious organism, growing in microaerophilic
      conditions with a temperature range between 37 degrees and 42 degrees C. Multiple
      types of media can be used to cultivate it; however, Mueller Hinton broth and
      agar support the best C. jejuni growth. Optimum atmosphere for C. jejuni is 85%
      N2, 10% CO2, and 5% O2.

PMID- 18729059
TI  - Genetic manipulation of Campylobacter jejuni.
AB  - Molecular manipulation has been a limiting factor in C. jejuni research for many
      years. Recent advances in molecular techniques adapted for C. jejuni have
      furthered our understanding of the organism. This unit is dedicated to common
      molecular tools in bacterial research specifically tailored for C. jejuni. These
      include colony PCR, DNA isolation, and RNA isolation. The unit also reviews
      techniques for genetic manipulation, such as the use of plasmids, natural
      transformation, electroporation, conjugation, and transposition. In addition, a
      reporter system, the arylsulfatase assay, can be used to study gene expression.

PMID- 18729060
TI  - Animal models of Listeria infection.
AB  - Listeria monocytogenes is an intracellular foodborne pathogen that causes
      listeriosis, an infection characterized by gastroenteritis, meningitis,
      encephalitis, and maternofetal infections in humans. L. monocytogenes enters the
      host via contaminated foods, invades the small intestine, translocates to
      mesenteric lymph nodes, and spreads to the liver, spleen, brain and, in pregnant
      women, the fetoplacental unit. Many pathogenicity tests for studying L.
      monocytogenes have been developed, including tests using laboratory animals. A
      number of small animal species can be experimentally infected with Listeria. Mice
      and guinea pigs can be infected either intragastrically or intravenously, and
      virulence evaluated either by enumerating bacteria within infected target organs
      or by evaluating the 50% lethal dose (LD50). Although mice and guinea pigs can be
      infected with Listeria by a variety of routes, the intragastric route is the most
      relevant to the human foodborne listeriosis.

PMID- 18729061
TI  - Techniques in aseptic rodent surgery.
AB  - Performing aseptic survival surgery in rodents can be challenging. This unit
      describes some basic principles to assist clinicians, researchers, and
      technicians in becoming proficient in performing aseptic rodent surgery.

PMID- 18729062
TI  - Production of polyclonal antisera.
AB  - Much of modern biology and biochemistry relies on the availability of highly
      specific antibodies for use in such ubiquitous techniques as
      immunohistochemistry, ELISAs, immunoprecipitation, and immunoblotting. Thus, the
      generation of large quantities of specific antibodies directed to proteins or
      peptides of interest is essential to the success of both basic and applied
      research programs. In addition, with the advent of antibody-based proteomic
      strategies for profiling protein expression and post-translational modification,
      a requirement for timely production of specific antibodies has emerged.
      Polyclonal antibodies derived from animals immunized with purified proteins or
      peptides are particularly valuable for use in the laboratory. This unit provides
      protocols for the production of polyclonal antisera specific for protein antigens
      in rabbits, rats, mice, and hamsters.

PMID- 18729063
TI  - ErbB2 transgenic mice: a tool for investigation of the immune prevention and
      treatment of mammary carcinomas.
AB  - The epidermal growth factor receptor belongs to a superfamily of receptor
      tyrosine kinases (RTK) that includes ErbB2. ErbB2 is involved in normal
      physiological processes, such as embryogenesis, cell proliferation,
      differentiation, adhesion motility, and apoptosis, while its malfunction or
      overexpression is responsible for development defects, diabetes, and cancer. The
      human ortholog of ErbB2 is referred as Her-2 (human ErbB2) while the rat ortholog
      is referred as neu (rat ErbB2). As ErbB2 is directly involved in carcinogenesis,
      mice transgenic for the rat neu oncogene allow straightforward assessment of the
      ability of drugs and vaccines to inhibit the progression of neu-driven cancer.
      Information from this model may provide indications on the efficacy of similar
      treatments in patients. This commentary provides key information regarding the
      use of these transgenic mouse models for evaluation of the efficacy of anti-tumor
      strategies.

PMID- 18729064
TI  - Measurement of proliferative responses of cultured lymphocytes.
AB  - Measurement of proliferative responses of human lymphocytes is a fundamental
      technique for the assessment of their biological responses to various stimuli.
      Most simply, this involves measurement of the number of cells present in a
      culture before and after the addition of a stimulating agent. This unit contains
      several different prototype protocols to measure the proliferative response of
      lymphocytes following exposure to mitogens, antigens, allogeneic or autologous
      cells, or soluble factors. Each of these protocols can be used in conjunction
      with an accompanying support protocol which contains methods for pulsing cultures
      with [3H]thymidine and determining incorporation of [3H]thymidine into DNA or
      assessing cell proliferation by nonradioactive methods, e.g., reduction of
      tetrazolium salts (MTT). The protocols described here provide an estimate of DNA
      synthesis and cell proliferation in an entire cell population, but do not provide
      information on the proliferation of individual cells. A protocol for CFSE
      labeling allows specific subpopulations of cells to be separated viably for
      further analysis.

PMID- 18729065
TI  - Clinical outcomes from a physiotherapist-led intra-articular hyaluronic acid
      injection clinic.
AB  - OBJECTIVES: To describe the clinical course of knee osteoarthritis following a
      single course of intra-articular hyaluronic acid (HA) injection clinic, and
      specifically to explore treatment withdrawal. DESIGN: Prospective consecutive
      case series with follow-up, set in an innovative physiotherapist-led clinic,
      based in a hospital orthopaedic surgery department. PARTICIPANTS: A total of 100
      patients with knee osteoarthritis referred to the clinic received a single course
      of five injections of Hyalgan. Patients were followed up in clinic at five, 13,
      26 and 52 weeks. The primary outcome measures were Western Ontario McMaster
      Universities Osteoarthritis Index (WOMAC) Likert 3.0 pain (0-20) and physical
      function (0-68) scores. In addition, at 13 and 26 weeks, patients were reviewed
      independently by an orthopaedic surgeon, with the option of withdrawing for
      alternative management those patients who had not responded. RESULTS: Ninety
      (90%) patients were successfully followed to study endpoint. Improvements were
      seen at five weeks and, to a lesser extent, at 13 weeks (mean reduction in WOMAC
      pain at 13 weeks = 1.3; 95% confidence interval [CI] 0.5, 2.0; mean reduction in
      WOMAC Physical Function at 13 weeks = 5.6; 95% CI 3.0, 8.1). Of 34 treatment
      withdrawals, most had returned to baseline levels by 13 weeks. The remaining 56
      patients maintained improvements up to 52 weeks, although the pattern of outcome
      was highly variable between individuals. Withdrawals and non-responders had
      higher initial pain severity. CONCLUSIONS: Physiotherapist-led intra-articular HA
      clinics are feasible. Clinical outcomes for individual patients are highly
      heterogeneous up to one year after injections. Patients with initially high
      levels of pain may be less likely to benefit.

PMID- 18729066
TI  - Phonological processing deficits and the acquisition of the alphabetic principle
      in a severely delayed reader: a case study.
AB  - At the end of first grade, TM did not know the alphabet and could read no words.
      He could not tap syllables in words, had difficulty producing rhyming words and
      retrieving the phonological representations of words, and he could not
      discriminate many phoneme contrasts. He learned letter-sound correspondences
      first for single-consonant onsets and then later for the final consonant in a
      word but had difficulty with letter-sound associations for vowels. TM's ability
      to select a printed word to match a spoken word on the basis of the initial or
      final letter and sound was interpreted as evidence of Ehri's phonetic-cue
      reading. Using the Glass Analysis method, the authors taught TM to read and he
      became an independent reader. We discuss how his phonological processing deficits
      contributed to his reading difficulties.

PMID- 18729067
TI  - Amyloid fibril composition is related to the phenotype of hereditary
      transthyretin V30M amyloidosis.
AB  - Swedish familial systemic amyloidosis with polyneuropathy (FAP) depends on a
      mutation leading to a methionine-for-valine substitution in transthyretin. The
      disease appears with different clinical manifestations, including age of onset
      and involvement of the heart. Liver transplantation is currently the only
      curative treatment, but progressive cardiomyopathy may occur post-transplant. Two
      amyloid deposition patterns have previously been described in the heart. In one,
      the amyloid consists partially of transthyretin fragments and is weakly stainable
      by Congo red, while in the other, only full-length molecules are found and the
      fibrils have a strong affinity for Congo red. The present study aimed to see
      whether these morphological and biochemical variations have clinical
      implications. Subcutaneous adipose tissue biopsies were taken from 33 patients
      with Val30Met FAP and examined by microscopy, electrophoresis and western blot.
      Clinical data included age, sex, duration of disease and echocardiographic
      determination of the interventricular septum (IVS) thickness. It was found that
      fibrils composed of only full-length transthyretin were associated with early age
      of onset (44.8 +/- 12.9 years), no clinical cardiac involvement and a strong
      affinity for Congo red. In contrast, presence of transthyretin fragments in the
      amyloid was associated with late age of onset (67.3 +/- 7.0 years), signs of
      cardiac involvement and weak Congo red staining. For each individual, the same
      molecular type of amyloid was found in different organs. This is the first report
      showing that variations in clinical appearance of familial ATTR amyloidosis are
      associated with specific structural differences in the amyloid fibrils, and
      therefore may have a molecular cause. The molecular type of amyloid can be
      determined from a subcutaneous fat tissue biopsy.

PMID- 18729068
TI  - Phagocyte-specific S100 proteins are released from affected mucosa and promote
      immune responses during inflammatory bowel disease.
AB  - Phagocyte-derived S100 proteins are endogenous activators of innate immune
      responses. S100A12 binds to the receptor for advanced glycation end-products,
      while complexes of S100A8/S100A9 (myeloid-related proteins, MRP8/14;
      calprotectin) are ligands of toll-like receptor 4. These S100 proteins can be
      detected in stool. In the present study we analyse the release of S100A12 and
      MRP8/14 from intestinal tissue. Specimens from patients with Crohn's disease (CD;
      n = 30), ulcerative colitis (UC; n = 30), irritable bowel syndrome (IBS; n = 30)
      or without inflammation (n = 30) were obtained during endoscopy. After 24 h
      culture, S100A12 and MRP8/14 were analysed in supernatants. Endoscopic,
      histological, laboratory and clinical disease activity measures were documented.
      We found an increased spontaneous release of S100A12 from tissue in inflammatory
      bowel disease (IBD). The release of S100A12 into the supernatants was 28-fold
      enhanced in inflamed tissue when compared to non-inflamed tissue (mean 46.9 vs.
      1.7 ng/ml, p < 0.0001). In active CD, release of S100A12 and MRP8/14 was strongly
      dependent on localization, with little release from sites of active ileal
      inflammation compared to colonic inflammation. This difference was more
      pronounced for S100A12 than for MRP8/14. S100A12 and MRP8/14 provoked up
      regulation of adhesion molecules and chemokines on human intestinal microvascular
      endothelial cells (HIMECs) isolated from normal colonic tissue. The direct
      release of phagocyte-derived S100 proteins from inflamed tissues may reflect
      secretion from infiltrating neutrophils (S100A12) and also monocytes or
      epithelial cells (MRP8/14). Via activation of pattern recognition receptors,
      these proteins promote inflammation in intestinal tissue. The enhanced mucosal
      release can explain the correlation of fecal markers with disease activity in
      IBD.

PMID- 18729069
TI  - Genomic alterations and gene expression in primary diffuse large B-cell lymphomas
      of immune-privileged sites: the importance of apoptosis and immunomodulatory
      pathways.
AB  - Primary diffuse large B-cell lymphomas of different immune-privileged sites (IP
      DLBCLs) share many clinical and biological features, such as a relatively poor
      prognosis, preferential dissemination to other immune-privileged sites, and
      deletion of the HLA region, which suggests that IP-DLBCL represents a separate
      entity. To further investigate the nature of IP-DLBCL, we investigated site
      specific genomic aberrations in 16 testicular, nine central nervous system (CNS),
      and 15 nodal DLBCLs using array CGH. We also determined minimal common regions of
      gain and loss. Using robust algorithms including multiple testing procedures and
      the ACE-it script, which is specifically designed for this task, the array CGH
      data were combined with gene expression data to explore pathways deregulated by
      chromosomal aberrations. Loss of 6p21.32-p25.3, including the HLA genes, was
      associated with both types of IP-DLBCL, whereas gain of 2p16.1-p25.3 was
      associated with nodal DLBCL. Gain of 12q15-q21.1 and 12q24.32-q24.33 was
      associated with CNS DLBCL and gain of 19q13.12-q13.43 with testicular DLBCL.
      Analysis of candidate genes in site-specific regions and minimal common regions
      revealed two major groups of genes: one involved in the immune response,
      including regulation of HLA expression, and the other involved in apoptosis,
      including the p53 pathway. Many of these genes were also involved in homozygous
      deletions or high-level gains. The presence of both shared and site-specific
      aberrations in CNS and testicular DLBCLs underlines the concept of IP-DLBCL but
      also indicates that IP-DLBCLs of the CNS and testis do not form a single entity.
      The observed aberrations emphasize the importance of the deregulation of anti
      tumour immune response and apoptosis pathways.

PMID- 18729071
TI  - Congratulations to Professor Ryoji Noyori on his 70th birthday.

PMID- 18729070
TI  - Amelioration of the premature ageing-like features of Fgf-23 knockout mice by
      genetically restoring the systemic actions of FGF-23.
AB  - Genetic ablation of fibroblast growth factor 23 from mice (Fgf-23(-/-)) results
      in a short lifespan with numerous abnormal biochemical and morphological
      features. Such features include kyphosis, hypogonadism and associated
      infertility, osteopenia, pulmonary emphysema, severe vascular and soft tissue
      calcifications, and generalized atrophy of various tissues. To determine whether
      these widespread anomalies in Fgf-23(-/-) mice can be ameliorated by genetically
      restoring the systemic actions of FGF-23, we generated Fgf-23(-/-) mice
      expressing the human FGF-23 transgene in osteoblasts under the control of the 2.3
      kb alpha1(I) collagen promoter (Fgf-23(-/-) /hFGF-23-Tg double mutants). This
      novel mouse model is completely void of all endogenous Fgf-23 activity, but
      produces human FGF-23 in bone cells that is subsequently released into the
      circulation. Our results suggest that lack of Fgf-23 activities results in
      extensive premature ageing-like features and early mortality of Fgf-23(-/-) mice,
      while restoring the systemic effects of FGF-23 significantly ameliorates these
      phenotypes, with the resultant effect being improved growth, restored fertility,
      and significantly prolonged survival of double mutants. With regard to their
      serum biochemistry, double mutants reversed the severe hyperphosphataemia,
      hypercalcaemia, and hypervitaminosis D found in Fgf-23(-/-) littermates; rather,
      double mutants show hypophosphataemia and normal serum 1,25-dihydroxyvitamin D(3)
      levels similar to pure FGF-23 Tg mice. These changes were associated with reduced
      renal expression of NaPi2a and 1 alpha-hydroxylase, compared to Fgf-23(-/-) mice.
      FGF-23 acts to prevent widespread abnormal features by acting systemically to
      regulate phosphate homeostasis and vitamin D metabolism. This novel mouse model
      provides us with an in vivo tool to study the systemic effects of FGF-23 in
      regulating mineral ion metabolism and preventing multiple abnormal phenotypes
      without the interference of native Fgf-23.

PMID- 18729072
TI  - "What next?" Congratulations!

PMID- 18729075
TI  - Increased KIT signalling with up-regulation of cyclin D correlates to accelerated
      proliferation and shorter disease-free survival in gastrointestinal stromal
      tumours (GISTs) with KIT exon 11 deletions.
AB  - Gastrointestinal stromal tumours (GISTs) with deletions in KIT exon 11 are
      characterized by higher proliferation rates and shorter disease-free survival
      times, compared to GISTs with KIT exon 11 point mutations. Up-regulation of
      cyclin D is a crucial event for entry into the G1 phase of the cell cycle, and
      links mitogenic signalling to cell proliferation. Signalling from activated KIT
      to cyclin D is directed through the RAS/RAF/ERK, PI3K/AKT/mTOR/EIF4E, and
      JAK/STATs cascades. ERK and STATs initiate mRNA transcription of cyclin D,
      whereas EIF4E activation leads to increased translation efficiency and reduced
      degradation of cyclin D protein. The aim of the current study was to analyse the
      mRNA and protein expression as well as protein phosphorylation of central hubs of
      these signalling cascades in primary GISTs, to evaluate whether tumours with KIT
      exon 11 deletions and point mutations differently utilize these pathways. GISTs
      with KIT exon 11 deletions had significantly higher mitotic counts, higher
      proliferation rates, and shorter disease-free survival times. In line with this,
      they had significantly higher expression of cyclin D on the mRNA and protein
      level. Furthermore, there was a significantly higher amount of phosphorylated
      ERK1/2, and a higher protein amount of STAT3, mTOR, and EIF4E. PI3K and
      phosphorylated AKT were also up-regulated, but this was not significant.
      Ultimately, GISTs with KIT exon 11 deletions had significantly higher
      phosphorylation of the central negative cell-cycle regulator RB. Phosphorylation
      of RB is accomplished by activated cyclin D/CDK4/6 complex, and marks a central
      event in the release of the cell cycle. Altogether, these observations suggest
      increased KIT signalling with up-regulation of cyclin D as the basis for the
      unfavourable clinical course in GISTs with KIT exon 11 deletions.

PMID- 18729076
TI  - Suppression of putative tumour suppressor gene GLTSCR2 expression in human
      glioblastomas.
AB  - Glioma tumour-suppressor candidate region gene 2 (GLTSCR2/PICT-1) is localized
      within the well-known 1.4 Mb tumour-suppressive region of chromosome 19q, which
      is frequently altered in various human tumours, including diffuse gliomas. Aside
      from its chromosomal localization, several lines of evidence, including PTEN
      phosphorylating and cell-killing activities, suggests that GLTSCR2 participates
      in the suppression of tumour growth and development. However, little is known
      about the biological functions and molecular mechanisms of GLTSCR2 as a tumour
      suppressor gene. We investigated the pathological significance of GLTSCR2
      expression in association with the development and progression of glioblastomas,
      the most common malignant brain tumour. We used real-time PCR and western blot
      analysis to examine the expression levels of GLTSCR2 mRNA and protein in
      glioblastomas, normal brain tissue and in non-glial tumour tissue of different
      origin, and found that GLTSCR2 expression is down-regulated in glioblastomas. In
      addition, direct sequencing analysis and fluorescence in situ hybridization
      clearly demonstrates the presence of genetic alterations, such as a nonsense
      mutation and deletion, in the GLTSCR2 gene in glioblastomas. Finally, our
      immunohistochemical study demonstrates that GLTSCR2 is sequentially down
      regulated according to the histological malignant progression of the astrocytic
      glial tumour. Taken together, our results suggest that GLTSCR2 is involved in
      astrocytic glioma progression.

PMID- 18729074
TI  - Identification of novel Smad2 and Smad3 associated proteins in response to TGF
      beta1.
AB  - Transforming growth factor-beta 1 (TGF-beta1) is an important growth inhibitor of
      epithelial cells and insensitivity to this cytokine results in uncontrolled cell
      proliferation and can contribute to tumorigenesis. TGF-beta1 signals through the
      TGF-beta type I and type II receptors, and activates the Smad pathway via
      phosphorylation of Smad2 and Smad3. Since little is known about the selective
      activation of Smad2 versus Smad3, we set out to identify novel Smad2 and Smad3
      interacting proteins in epithelial cells. A non-transformed human cell line was
      transduced with Myc-His(6)-Smad2 or Myc-His(6)-Smad3-expressing retrovirus and
      was treated with TGF-beta1. Myc-His(6)-Smad2 or Myc-His(6)-Smad3 was purified by
      tandem affinity purification, eluates were subject to SDS-PAGE and Colloidal Blue
      staining, and select protein bands were digested with trypsin. The resulting
      tryptic peptides were analyzed by liquid chromatography (LC) and tandem mass
      spectrometry (MS/MS) and the SEQUEST algorithm was employed to identify proteins
      in the bands. A number of proteins that are known to interact with Smad2 or Smad3
      were detected in the eluates. In addition, a number of putative novel Smad2 and
      Smad3 associated proteins were identified that have functions in cell
      proliferation, apoptosis, actin cytoskeleton regulation, cell motility,
      transcription, and Ras or insulin signaling. Specifically, the interaction
      between Smad2/3 and the Cdc42 guanine nucleotide exchange factor, Zizimin1, was
      validated by co-immunoprecipitation. The discovery of these novel Smad2 and/or
      Smad3 associated proteins may reveal how Smad2 and Smad3 are regulated and/or
      uncover new functions of Smad2 and Smad3 in TGF-beta1 signaling.

PMID- 18729077
TI  - Beneficial effects of prolonged systemic administration of PlGF on late outcome
      of post-ischaemic myocardial performance.
AB  - Recent evidence indicates that an imbalance between cardiomyocyte hypertrophy and
      blood vessel growth in the remote myocardium may contribute to heart failure in
      ischaemic heart disease. It remains, however, largely unknown which angiogenic
      factors are capable of stimulating vessel growth in the remote myocardium after
      myocardial infarction (MI) and whether systemic, rather than local,
      administration of such factors suffices to ameliorate post-MI cardiac recovery.
      We therefore analysed the effect of systemic placental growth factor (PlGF)
      delivery on myocardial recovery post-MI in mice. MI was induced by permanent
      ligation of the left anterior descending coronary (LAD) artery in C57Bl6/J mice,
      followed by systemic injection of a PlGF adenovirus, resulting in elevated
      circulating levels of PlGF for 4 weeks. Functional and morphological analysis
      revealed that PlGF treatment induced cardiomyocyte hypertrophy and improved
      cardiac recovery at day 28 post-MI. PlGF stimulated angiogenesis in the infarct
      border and vessel enlargement in the remote myocardium. In this mouse model,
      capillary-to-cardiomyocyte ratios in the remote myocardium were maintained post
      MI, but PlGF increased the vascular perfusion area in balance with the
      cardiomyocyte hypertrophy. Overall, systemic delivery of PlGF improves cardiac
      performance and promotes adaptive remodelling of the post-MI heart.

PMID- 18729078
TI  - Functional decoupling of BOLD and gamma-band amplitudes in human primary visual
      cortex.
AB  - Although functional magnetic resonance imaging is an important tool for measuring
      brain activity, the hemodynamic blood oxygenation level dependent (BOLD) response
      is only an indirect measure of neuronal activity. Converging evidence obtained
      from simultaneous recording of hemodynamic and electrical measures suggest that
      the best correlate of the BOLD response in primary visual cortex is gamma-band
      oscillations ( approximately 40 Hz). Here, we examined the coupling between BOLD
      and gamma-band amplitudes measured with magntoencephalography (MEG) in human
      primary visual cortex in 10 participants. In Experiment A, participants were
      exposed to grating stimuli at two contrast levels and two spatial frequencies and
      in Experiment B square and sine wave stimuli at two spatial frequencies. The
      amplitudes of both gamma-band oscillations and BOLD showed tuning with stimulus
      contrast and stimulus type; however, gamma-band oscillations showed a 300%
      increase across two spatial frequencies, whereas BOLD exhibited no change. This
      functional decoupling demonstrates that increased amplitude of gamma-band
      oscillations as measured with MEG is not sufficient to drive the subsequent BOLD
      response.

PMID- 18729079
TI  - Disentangling the prefrontal network for rule selection by means of a non-verbal
      variant of the Wisconsin Card Sorting Test.
AB  - This study disentangles the prefrontal network underlying executive functions
      involved in the Wisconsin Card Sorting Test (WCST). During the WCST, subjects
      have to perform two key processes: first, they have to derive the correct sorting
      rule for each trial by trial-and-error, and, second, they have to detect when
      this sorting rule is changed by the investigator. Both cognitive processes
      constitute key components of the executive system, which is subserved by the
      prefrontal cortex. For the current fMRI experiment, we developed a non-verbal
      variant of the WCST. Subjects were instructed either to respond according to a
      given sorting rule or to detect the correct sorting rule, like in the original
      version of the WCST. Data were obtained from 14 healthy male volunteers and
      analysed using SPM and a random effects model. All conditions activated a fronto
      parietal network, which was generally more active when subjects had to search for
      the correct sorting rule than when the rule was announced beforehand. Significant
      differences between these two conditions were seen in the dorsolateral prefrontal
      cortex (PFC) and the parietal lobe. In addition, the data provided new evidence
      for the assumption of differentiated roles of the left and right prefrontal
      cortex. Although the right PFC showed a general involvement in response selection
      and the execution of goal directed responses, based on given rules, the left PFC
      was only activated when inductive reasoning and feedback integration was
      required.

PMID- 18729080
TI  - Helenalin-mediated post-transcriptional regulation of p21(Cip1) inhibits 3T3-L1
      preadipocyte proliferation.
AB  - We have previously shown that post-transcriptional mechanisms involving the 26S
      proteasome regulate the cyclin-dependent kinase inhibitors (CKIs), p21(Cip1) and
      p27(Kip1) during preadipocyte proliferation. Earlier studies further demonstrated
      that the anti-inflammatory, anti-carcinogenic phytochemical, helenalin is a
      potent inhibitor of periodic Skp2 accumulation, an F-box protein mediating SCF E3
      ligase ubiquitylation and degradation of both CKIs during S phase progression.
      Data presented here demonstrate that helenalin dose-dependently induced G1 arrest
      of synchronously replicating 3T3-L1 preadipocytes. This effect occurred in the
      absence of discernable indices of cell toxicity or apoptosis under the conditions
      used in this study. Our results demonstrate that helenalin markedly increased p21
      protein accumulation in both density-arrested and proliferating preadipocytes in
      a dose-dependent manner. This increase in p21 protein abundance occurred without
      change in mRNA transcript demonstrating that post-transcriptional mechanisms were
      involved. This notion was further supported by the modest accumulation of
      polyubiquitylated p21 following treatment with helenalin suggesting that
      suppression of targeted p21 proteolysis by the 26S proteasome contributed to
      helenalin-mediated p21 accumulation. The increase in p21 protein was
      compartmentalized to the nucleus where p21 is known to inhibit cell cycle
      progression. Finally, helenalin increased protein-protein interactions between
      p21 and cyclin-dependent kinase 2 (Cdk2) which may account in part for the anti
      proliferative effect in 3T3-L1 preadipocytes.

PMID- 18729082
TI  - New insights into cardiovascular and lipid metabolomics.
AB  - Metabolomics is the study of metabolite profiles in biological samples,
      particularly urine, saliva, blood plasma and fat biopsies. The metabolome is now
      considered by some to be the most predictive phenotype: consequently, the
      comprehensive and quantitative study of metabolites is a desirable tool for
      diagnosing disease, identifying new therapeutic targets and enabling appropriate
      treatments. A wealth of information about metabolites has been accumulated with
      global profiling tools and several candidate technologies for metabolomic studies
      are now available. Many high-throughput metabolomics methodologies are currently
      under development and have yet to be applied in clinical practice on a routine
      basis. In the cardiovascular field, few recent metabolomic studies have been
      reported so far. This minireview provides an updated overview of alternative
      technical approaches for metabolomics studies and reviews initial applications of
      metabolomics that relate to both cardiovascular disease and lipid metabolism
      research.

PMID- 18729081
TI  - Activating transcription factor 4 is critical for proliferation and survival in
      primary bone marrow stromal cells and calvarial osteoblasts.
AB  - Activating transcription factor 4 (ATF4) is essential for bone formation.
      However, the mechanism of its actions in bone is poorly understood. The present
      study examined the role for ATF4 in the regulation of proliferation and survival
      of primary mouse bone marrow stromal cells (BMSCs) and osteoblasts. Results
      showed that Atf4(-/-) cells display a severe proliferative defect as measured by
      multiple cell proliferation assays. Cell cycle progression of Atf4(-/-) BMSCs was
      largely delayed with significant G1 arrest. Expression of cyclin D1 was decreased
      both at the mRNA and protein level. A similar proliferation defect was observed
      in Atf4(-/-) calvarial periosteal osteoblasts when compared with wt control.
      Knocking down Atf4 mRNA by small interfering RNA in MC3T3-E1 subclone 4
      preosteoblasts markedly reduced expression of cyclin D1 and cell proliferation.
      In contrast, overexpression of ATF4 increased cyclin D1 expression as well as
      cell proliferation in Atf4(-/-) BMSCs. In addition, apoptosis was significantly
      increased in Atf4(-/-) BMSCs and calvarial periosteal osteoblasts relative to wt
      controls. Taken together, these results for the first time demonstrate that ATF4
      is a critical regulator of proliferation and survival in BMSCs and osteoblasts in
      vitro and in vivo.

PMID- 18729083
TI  - Changes in MicroRNA expression patterns in human fibroblasts after low-LET
      radiation.
AB  - Exposure to radiation provokes cellular responses controlled in part by gene
      expression networks. MicroRNAs (miRNAs) are small non-coding RNAs which mostly
      regulate gene expression by degrading the messages or inhibiting translation.
      Here, we investigated changes in miRNA expression patterns after low (0.1 Gy) and
      high (2.0 Gy) doses of X-ray in human fibroblasts. At early (0.5 h) and late (6
      and 24 h) time points, irradiation caused qualitative and quantitative
      differences in the down-regulation of miRNA levels, including miR-92b, 137, 660,
      and 656. A transient up-regulation of miRNAs was observed after 2 h post
      irradiation following high doses of radiation, including miR-558 and 662.
      MicroRNA levels were inversely correlated with targets from mRNA and proteomic
      profiling after 2.0 Gy of radiation. MicroRNAs miR-579, 608, 548-3p, and 585 are
      noted for targeting genes involved in radioresponsive mechanisms, such as cell
      cycle checkpoint and apoptosis. We suggest here a model in which miRNAs may act
      as "hub" regulators of specific cellular responses, immediately down-regulated so
      as to stimulate DNA repair mechanisms, followed by up-regulation involved in
      suppressing apoptosis for cell survival. Taken together, miRNAs may mediate
      signaling pathways in sequential fashion in response to radiation, and may serve
      as biodosimetric markers of radiation exposure.

PMID- 18729084
TI  - Differential regulation of human and mouse telomerase reverse transcriptase
      (TERT) promoter activity during testis development.
AB  - In adult testis, telomerase activity is exclusively detectable during the early
      steps of spermatogenesis and is downregulated during differentiation to
      spermatozoa. Knowledge about telomerase activity during testis development from
      birth to adulthood is still scarce. Telomerase activity is regulated primarily
      via the transcriptional initiation of TERT expression which encodes its catalytic
      subunit. We used the hTERTp-lacZ transgenic mouse model that expresses the
      bacterial lacZ reporter gene under the control of an 8.0-kbp human TERT promoter
      fragment to analyze simultaneously endogenous mouse Tert gene expression as well
      as human TERT promoter activity during mouse testis development. We show that
      human TERT promoter activity increased during puberty and was highest in adult
      mouse testis whereas mouse Tert expression and telomerase activity were found to
      be high in testis from the earliest time point tested (6 days postpartum).
      Histological analysis revealed that beta-galactosidase expression, encoded by the
      lacZ reporter gene, is present in all seminiferous tubules in adult testis, but
      in a subset of tubules before puberty. We further analyzed the expression of SCF/
      c-KIT, which was described to regulate spermatogonia proliferation and mouse Tert
      expression, in prepubertal and adult testis by immunohistochemistry. Whereas SCF
      and c-KIT were detectable in all seminiferous tubules, a spatial and preclusive
      expression pattern of human TERT promoter activity and activated c-KIT (p-c-KIT
      Tyr 567/569) was observed in prepubertal testes.

PMID- 18729085
TI  - Dose-dependent growth inhibition in vivo of PC-3 prostate cancer with a reduction
      in tumoral growth factors after therapy with GHRH antagonist MZ-J-7-138.
AB  - BACKGROUND: Antagonists of growth hormone-releasing hormone (GHRH) inhibit the
      growth of various cancers and affect tumoral growth factors. METHODS: We
      investigated the effect of a new GHRH antagonist MZ-J-7-138 at doses of 1.25,
      2.5, 5 and 10 microg/day s.c. on the growth of PC-3 human androgen independent
      prostate cancers xenografted s.c. into nude mice. Binding assays were used to
      investigate GHRH receptors. The levels of IGF-II and VEGF in tumors were measured
      by radioimmunoassays. RESULTS: Treatment with 2.5, 5, and 10 microg/day MZ-J-7
      138 caused a significant dose-dependent growth reduction of PC-3 tumors. The
      greatest inhibition of 78% was obtained with 10 microg/day. The suppression of
      IGF-II protein levels in tumors was seen at all doses of MZ-J-7-138, but only 10
      microg dose induced a significant inhibition. MZ-J-7-138 also reduced VEGF
      protein levels, the inhibition being significant at doses of 5 and 10 microg.
      Specific high affinity binding sites for GHRH were found on PC-3 tumors using
      (125)I-labeled GHRH antagonist JV-1-42. MZ-J-7-138 displaced radiolabeled JV-1-42
      with an IC(50) of 0.32 nM indicating its high affinity to GHRH receptors. Real
      time PCR analyses detected splice variant 1 (SV1) of GHRH receptor (GHRH-R) as
      well as pituitary type of GHRH-R and GHRH ligand. CONCLUSION: Our results
      demonstrate the efficacy of GHRH antagonist MZ-J-7-138 in suppressing growth of
      PC-3 prostate cancer at doses lower than previous antagonists. The reduction of
      levels of growth factors such as VEGF and IGF-II in tumors by GHRH antagonist was
      correlated with the suppression of tumor growth.

PMID- 18729086
TI  - Synthesis, crystal structure, and DNA-cleaving behavior of 5-substituted benzene
      1,3-bis(methylene)-spaced dinuclear copper(II) complexes.
AB  - Three meta-dicopper complexes, 1-3, based on 5-substituted 1,3-xylylene spacer
      have been synthesized. These complexes are capable of inducing the transformation
      of supercoiled DNA (pUC19) to its nicked and linear DNA form in the presence of
      ascorbate, and their DNA nicking efficiency can be correlated to their DNA
      binding ability. The cleavage mechanism is similar to that of the non-substituted
      meta-dicopper complex A. Amongst the three complexes, 5-(aminomethyl)-substituted
      complex 3 displayed a higher DNA-binding ability and nicking efficiency than
      unsubstituted complex A. The CD-spectroscopic study and structural analysis imply
      that the different CuCu distances and DNA binding modes induced by different 5
      substituents on benzene-1,3-bis(methylene) spacer may be responsible for the
      different DNA cleaving behavior of meta-dicopper complexes.

PMID- 18729087
TI  - The thulium complex of 1,4,7,10-tetrakis{[N-(1H-imidazol-2-yl)carbamoyl]methyl}
      1,4,7,10-tetraazacyclododecane (dotami) as a ParaCEST contrast agent.
AB  - 1,4,7,10-Tetrakis{[N-(1H-imidazol-2-yl)carbamoyl]methyl}-1,4,7,10
      tetraazacyclododecane (dotami), a tetra(1H-imidazol-2-yl) derivative of the well
      studied octadentate 1,4,7,10-tetrakis[(carbamoyl)methyl]-1,4,7,10
      tetraazacyclododecane (dotam) ligand, was synthesized by reaction of 1,4,7,10
      tetraazacyclododecane with N-(1H-imidazol-2-yl)chloroacetamide in high yield. Its
      tricationic thulium complex was isolated as a water-soluble chloride salt. The
      detection of the mildly acidic amide and amine protons by direct proton NMR in
      aqueous solution was unsuccessful, but such exchangeable protons could be
      detected via their chemical exchange-dependent saturation transfer (CEST) effect.
      The observed CEST effect was distinctly different from that found for respective
      dotam complexes and is, therefore, ascribed to exchangeable protons associated
      with the imidazole substituent.

PMID- 18729088
TI  - The influence of auranofin, a clinically established antiarthritic gold drug, on
      bone metabolism: analysis of its effects on human multipotent adipose-derived
      stem cells, taken as a model.
AB  - Auranofin is a gold-based antiarthritic drug in clinical use for more that 25
      years. However, in spite of a long established use, its specific effects on bone
      metabolism are still greatly controversial. We have analyzed in vitro the actions
      of auranofin on human multipotent adipose-derived stem (hMADS) cells, used as a
      model for bone metabolism, since these cells were reported to undergo
      osteogenesis both in vitro and in vivo. Cytotoxicity of auranofin on hMADS cells,
      differentiated into osteoblasts, was initially assessed. Thereafter, the
      consequences of exposure to nontoxic but clinically relevant auranofin
      concentrations were analyzed by monitoring the seleno-protein glutathione
      peroxidase 3 or alkaline phosphatase, a characteristic biomarker of osteogenesis.
      Notably, we found that chronic treatment with auranofin alters only weakly the
      levels of alkaline phosphatase, thus implying an overall modest effect on
      osteogenesis. In contrast, auranofin turned out to greatly affect glutathione
      peroxidase 3 activity. The possible medical implications of these findings are
      discussed.

PMID- 18729089
TI  - Eutectic phase in water-ice: a self-assembled environment conducive to metal
      catalyzed non-enzymatic RNA polymerization.
AB  - Information and catalytic polymers play an essential role in contemporary
      cellular life, and their emergence must have been crucial during the complex
      processes that led to the assembly of the first living systems. Polymerization
      reactions producing these molecules would have had to occur in aqueous medium,
      which is known to disfavor such reactions. Thus, it was proposed early on that
      these polymerizations had to be supported by particular environments, such as
      mineral surfaces and eutectic phases in water-ice, which would have led to the
      concentration of the monomers out of the bulk aqueous medium and their
      condensation. This review presents the work conducted to understand how the
      eutectic phases in water-ice might have promoted RNA polymerization, thereby
      presumably contributing to the emergence of the ancient information and catalytic
      system envisioned by the 'RNA-World' hypothesis.

PMID- 18729090
TI  - Influence of carbonate on the binding of carboplatin to DNA.
AB  - The reaction of aged carboplatin (reaction of carboplatin in 24 mM NaHCO(3) for
      45 h, 37 degrees, pH 8.6) with pBR322 DNA at 0 < r < 2.8, where r = [drug]/[DNA
      bp], in 24 mM HEPES buffer, pH 7.4, for 24 h, followed by agarose gel
      electrophoresis showed DNA mobility changes consistent with unwinding closed
      circular DNA. However, identical experiments conducted in a two-buffer system, 24
      mM HEPES plus 24 mM carbonate, showed no DNA mobility changes, indicating that
      carbonate blocks formation of the 1,2 intrastrand cross-link on DNA. Studies with
      aged carboplatin and with cisplatin carried out with ca. 4.0 < r < 10.0 in the
      two-buffer system show that some DNA binding and unwinding occurs for both drugs.
      Since carbonate inhibits the binding of aged carboplatin and cisplatin to DNA,
      carbonate present in the body likely modulates the reactivity of these drugs with
      a variety of biological targets including DNA.

PMID- 18729091
TI  - Addition of DNA to Cr(VI) and cytochrome b5 containing proteoliposomes leads to
      generation of DNA strand breaks and Cr(III) complexes.
AB  - Chromium (Cr) is a cytotoxic metal that can be associated with a variety of types
      of DNA damage, including Cr-DNA adducts and strand breaks. Prior studies with
      purified human cytochrome b(5) and NADPH:P450 reductase in reconstituted
      proteoliposomes (PLs) demonstrated rapid reduction of Cr(VI) (hexavalent
      chromium, as CrO(4)(2-), and the generation of Cr(V), superoxide (O(2)(*-)), and
      hydroxyl radical (HO(*)). Studies reported here examined the potential for the
      species produced by this system to interact with DNA. Strand breaks of purified
      plasmid DNA increased over time aerobically, but were not observed in the absence
      of O(2). Cr(V) is formed under both conditions, so the breaks are not mediated
      directly by Cr(V). The aerobic strand breaks were significantly prevented by
      catalase and EtOH, but not by the metal chelator diethylenetriaminepentaacetic
      acid (DTPA), suggesting that they are largely due to HO(*) from Cr-mediated redox
      cycling. EPR was used to assess the formation of Cr-DNA complexes. Following a 10
      min incubation of PLs, CrO(4)(2-), and plasmid DNA, intense EPR signals at g=5.7
      and g=5.0 were observed. These signals are attributed to specific Cr(III)
      complexes with large zero field splitting (ZFS). Without DNA, the signals in the
      g=5 region were weak. The large ZFS signals were not seen, when Cr(III)Cl(3) was
      incubated with DNA, suggesting that the Cr(III)-DNA interactions are different
      when generated by the PLs. After 24 h, a broad signal at g=2 is attributed to
      Cr(III) complexes with a small ZFS. This g=2 signal was observed without DNA, but
      it was different from that seen with plasmid. It is concluded that EPR can detect
      specific Cr(III) complexes that depend on the presence of plasmid DNA and the
      manner in which the Cr(III) is formed.

PMID- 18729093
TI  - Modelling low-potential [Fe4S4] clusters in proteins.

PMID- 18729092
TI  - Effects of vanadium-containing compounds on membrane lipids and on microdomains
      used in receptor-mediated signaling.
AB  - There is increasing evidence for the involvement of plasma membrane microdomains
      in insulin receptor function. Moreover, disruption of these structures, which are
      typically enriched in sphingomyelin and cholesterol, results in insulin
      resistance. Treatment strategies for insulin resistance include the use of
      vanadium (V) compounds which have been shown in animal models to enhance insulin
      responsiveness. One possible mechanism for insulin-enhancing effects might
      involve direct effects of V compounds on membrane lipid organization. These
      changes in lipid organization promote the partitioning of insulin receptors and
      other receptors into membrane microdomains where receptors are optimally
      functional. To explore this possibility, we have used several strategies
      involving V complexes such as [VO(2)(dipic)](-) (pyridin-2,6
      dicarboxylatodioxovanadium(V)), decavanadate (V(10)O(28)(6-), V(10)), BMOV
      (bis(maltolato)oxovanadium(IV)), and [VO(saltris)](2) (2-salicylideniminato-2
      (hydroxymethyl)-1,3-dihydroxypropane-oxovanadium(V)). Our strategies include an
      evaluation of interactions between V-containing compounds and model lipid
      systems, an evaluation of the effects of V compounds on lipid fluidity in
      erythrocyte membranes, and studies of the effects of V-containing compounds on
      signaling events initiated by receptors known to use membrane microdomains as
      signaling platforms.

PMID- 18729094
TI  - Formation of {Cu2(III)(mu-O)2}2+ core due to dioxygen reactivity of a copper(I)
      complex supported by a new hybrid tridentate ligand: reaction with exogenous
      substrates.
AB  - Reaction of a Cu(I) complex of a hybrid tridentate ligand, encompassing [2
      (pyridin-2-yl)ethyl]amine and dimethyl-substituted ethylalkylamine with dioxygen,
      generates in acetone at -80 degrees putative bis(mu-oxo)dicopper(III)
      intermediate. Structural characterization of a PPh(3)-adduct of a mononuclear
      Cu(I) complex of this new ligand has been achieved. This ligand coordinates in a
      facial mode utilizing three N-atoms (-CH(2)CH(2)-Py, -CH(2)CH(2)NMe(2), and 
      NCH(2)Ph). Reactivity of bis(mu-oxo)dicopper(III) intermediate toward exogenous
      substrates (2,4-di(tert-butyl)phenol and 2,4,6-tri(tert-butyl)phenol) has also
      been investigated.

PMID- 18729095
TI  - Elucidation of the interactions of an anticancer ruthenium complex in clinical
      trials with biomolecules utilizing capillary electrophoresis hyphenated to
      inductively coupled plasma-mass spectrometry. Short communication.
AB  - The application of capillary electrophoresis (CE) combined with highly sensitive
      inductively-coupled-plasma mass spectrometric (ICP-MS) detection allows the
      interactions of metal complexes with biomolecules to be characterized. This
      technique has been used to provide new insights into the mode of action of the
      ruthenium-based anticancer drug candidate indazolium [trans-tetrachlorobis(1H
      indazole)ruthenate(III)] (KP1019). While the compound binds rapidly and
      efficiently to serum proteins, especially albumin, its reactivity towards the
      model DNA compound 2'-deoxyguanosine 5'-monophosphate (5'-dGMP) is moderate.

PMID- 18729096
TI  - Action mechanism of insulin-mimetic vanadyl-allixin complex.
AB  - In the 21st century, there has been a dramatic worldwide increase in the
      prevalence of metabolic syndromes, including diabetes mellitus (DM). Several
      synthetic pharmaceutical agents have been developed and used for the treatment of
      type-2 DM; however, these compounds have several problems such as side effects,
      hypoglycemia, and weight gain. Therefore, new drugs are required for DM therapy.
      We have proposed that some vanadyl complexes function as potent insulin-mimetic
      and antidiabetic agents in type-1 and type-2 DM animal models. In this article,
      we review the possible action mechanism of insulin-mimetic and antidiabetic
      vanadyl complexes, focusing on a recently proposed complex,
      bis(allixinato)oxovanadium(IV), with respect to the insulin-signaling pathway in
      cultured adipocytes.

PMID- 18729097
TI  - Interaction of flavin adenine dinucleotide (FAD) with a glassy carbon electrode
      surface.
AB  - The interaction of flavin adenine dinucleotide (FAD) with a glassy carbon
      electrode (GCE) surface was investigated in terms of the FAD adsorption
      thermodynamics and kinetics, the subsequent electroreduction mechanism, and the
      corresponding electron-transfer rate. The kinetics of FAD electroreduction at the
      GCE was found to be an adsorption-controlled process. A set of electroreduction
      kinetic parameters was calculated: the true number of electrons involved in the
      FAD reduction, n=1.76, the apparent transfer coefficient, alpha(app)=0.41, and
      the apparent heterogeneous electron-transfer rate constant, k(app)=1.4 s(-1). The
      deviation of the number of exchanged electrons from the theoretical value for the
      complete reduction of FAD to FADH(2) (n=2) indicates that a small portion of FAD
      goes to a semiquinone state during the redox process. The FAD adsorption was well
      described by the Langmuir adsorption isotherm. The large negative apparent Gibbs
      energy of adsorption (DeltaG(ads)=-39.7 +/-0.4 kJ mol(-1)) indicated a highly
      spontaneous and strong adsorption of FAD on the GCE. The energetics of the
      adsorption process was found to be independent of the electrode surface charge in
      the electrochemical double-layer region. The kinetics of FAD adsorption was
      modeled using a pseudo-first-order kinetic model.

PMID- 18729098
TI  - Hydrolysis and cytotoxic properties of osmium(II)/(III)-DMSO-azole complexes.
      Short communication.
AB  - The antiproliferative properties of the osmium(II) complexes cis,fac
      [Os(II)Cl(2)(DMSO)(3)(L)] and trans,cis,cis-[Os(II)Cl(2)(DMSO)(2)(L)(2)] (L = 1H
      pyrazole, 1H-imidazole) were studied in three human cancer cell lines, namely 41M
      (ovary), SK-BR-3 (breast), and SW480 (colon). Their activities were compared with
      those of osmium(III) and ruthenium(III) NAMI-A type complexes on HT-29 (colon)
      and SK-BR-3 cancer cell lines. While IC(50) values of all the Os(II) complexes
      were found to be >1000 microM in all cell lines, Os and Ru-NAMI-A type complexes
      showed remarkable antiproliferative activity. The marginal in vitro cytotoxicity
      of the Os(II) compounds is presumably attributed to their resistance to
      hydrolysis. However, the Os-NAMI-A complexes, which are also kinetically stable
      in aqueous solution, showed reasonable antiproliferative activity in vitro when
      compared with the analogous Ru compounds and with the Os(II)-DMSO-azole species,
      indicating that hydrolysis might be not a prerequisite for the antitumor activity
      of Os-NAMI-A type complexes.

PMID- 18729100
TI  - Terpene conjugates of diaminedichloridoplatinum(II) complexes: antiproliferative
      effects in HL-60 leukemia, 518A2 melanoma, and HT-29 colon cancer cells.
AB  - Twenty-eight [6-(aminomethyl)nicotinate]dichloridoplatinum(II) complexes 1
      esterified with various terpene alcohols either directly or via alkyl spacers
      were tested for antiproliferative activity in human 518A2 melanoma and HL-60
      leukemia cells. Generally, conjugates with menthanes and polycyclic
      sesquiterpenes attached via propane-1,2-diyl spacers were most active. In the
      melanoma cells, the propane-1,2-diyl-spacered conjugates of (-)-menthol (1a(2')),
      (+)-neomenthol (1b(2')), (-)-carvomenthol (1h(2')), and (-)-isolongifolol
      (1n(2')) displayed growth inhibition at IC(50)<4 microM which is ten times
      smaller than that of cisplatin. The stationary diamino ligand was also crucial.
      The (-)-menthyl ester complexes with 2,3-diaminopropanoate (9a) and 2,4
      diaminobutanoate (10a) ligands caused a greater and persistent growth inhibition
      in HT-29 colon cancer cells upon long-term exposure when compared to the 6
      (aminomethyl)nicotinate analogue 1a. The cedrenyl ester 1l and the
      menthoxyisopropyl ester 1a(2') proved most efficacious in all three tumor cell
      lines. The DNA binding of complexes 1 was assessed by electrophoretic band-shift
      experiments and found correlated to the terpene structure but not to the observed
      antiproliferative activities.

PMID- 18729099
TI  - Phosphite-derivatized ruthenium-carbohydrate complexes in the catalytic hydration
      of nitriles. short communication.
AB  - The synthesis of metal complexes with bioligands is one option to introduce
      chirally defined ligands to catalysts. Herein, the hydration of nitriles to the
      corresponding carboxamides by use of ruthenium(II) complexes is described, which
      were obtained by attaching derivatives of the 3,5,6-bicyclophosphite-alpha-D
      glucofuranoside ligand.

PMID- 18729101
TI  - Liposomal forms of rhenium cluster compounds: enhancement of biological activity.
AB  - Liposomal formulations of dinuclear cluster rhenium (Re) compounds were used in
      biochemical trials. Interaction of liposomal forms of some Re compounds with red
      blood cells in experiments in vitro showed strong cell-stabilizing properties. In
      the models of tumor growth and hemolytic anemia in vivo, liposomal forms had
      better therapeutic effects in comparison with their solutions. The process of
      formation of liposomes of cluster Re compounds with different organic ligands was
      investigated by the method of electronic absorption spectra and mechanism of
      their interactions with lipids is proposed. Encapsulation of cluster Re compounds
      to lipid coating may have activation significance for the quadruple Re-Re bond.

PMID- 18729103
TI  - Delphinidin, an anthocyanidin in pigmented fruits and vegetables, induces
      apoptosis and cell cycle arrest in human colon cancer HCT116 cells.
AB  - Because of unsatisfactory treatment options for colon cancer, there is a need to
      develop novel preventive approaches for this malignancy. One such strategy is
      through chemoprevention by the use of non-toxic dietary substances and botanical
      products. Delphinidin, an anthocyanidin in pigmented fruits and vegetables,
      possesses strong anti-oxidant and anti-inflammatory properties. In the present
      study, we investigated the antiproliferative and proapoptotic properties of
      delphinidin in human colon cancer HCT116 cells. We found that treatment of cells
      with delphinidin (30-240 microM; 48 h) resulted in (i) decrease in cell viability
      (ii) induction of apoptosis, (iii) cleavage of PARP, (iv) activation of caspases
      3, -8, and -9, (v) increase in Bax with a concomitant decrease in Bcl-2 protein,
      and (vi) G2/M phase cell cycle arrest. NF-kappaB provides a mechanistic link
      between inflammation and cancer, and is a major factor controlling the ability of
      both pre-neoplastic and malignant cells to resist apoptosis-based tumor
      surveillance mechanisms. We therefore, determined the effect of delphinidin on NF
      kappaB signaling pathway. The immunoblot, ELISA and EMSA analysis demonstrated
      that the treatment of HCT116 cells with delphinidin resulted in the inhibition of
      (i) IKKalpha, (ii) phosphorylation and degradation of IkappaBalpha, (iii)
      phosphorylation of NF-kappaB/p65 at Ser(536), (iv) nuclear translocation of NF
      kappaB/p65, (v) NF-kappaB/p65 DNA binding activity, and (vi) transcriptional
      activation of NF-kappaB. Our results suggest that delphinidin treatment of HCT116
      cells suppressed NF-kappaB pathway, resulting in G2/M phase arrest and apoptosis.
      We suggest that delphinidin could have potential in inhibiting colon cancer
      growth.

PMID- 18729105
TI  - An acid-base-controllable [c2]daisy chain.

PMID- 18729104
TI  - Bicalutamide inhibits androgen-mediated adhesion of prostate cancer cells exposed
      to ionizing radiation.
AB  - BACKGROUND: Cell adhesion plays an important role in proliferation, metastasis,
      and tumor growth and may represent a potential vulnerability in treatment of
      prostate cancer patients. Bicalutamide (Casodex) has been used as an anti
      androgen agent for prostate cancer patients during hormone ablation therapy. This
      study focuses on the effect of Bicalutamide on cell adhesion to fibronectin (FN)
      in prostate cancer cells. METHODS: Androgen-dependent LNCaP prostate cancer cells
      were stimulated with androgen before being irradiated with doses of 0, 5, 10, or
      15 Gy. Cell adhesion to fibronectin was then measured to ascertain androgen's
      role in integrin mediated prostate cancer cell adhesion. Flow cytometry was used
      to analyze surface expression of integrin subtypes in LNCaP cells. RESULTS: LNCaP
      cell adhesion to FN was significantly increased by stimulation with androgen when
      treated with 10 or 15 Gy ionizing radiations but not at 0 or 5 Gy. This increase
      was inhibited by treatment with Bicalutamide. LNCaP cells exposed to high dose
      radiation showed an increased expression of alpha(V) and beta(1) integrins in
      response to androgen treatment while Bicalutamide abolished this effect.
      CONCLUSIONS: Our data show that Bicalutamide inhibits the effect of androgen on
      cell adhesion to FN through changes of integrin subtypes in cells given high dose
      radiation. This suggests new molecular targets and possible treatment strategies
      for prostate cancer patients to improve the outcome during hormone ablation
      therapy and radiation therapy.

PMID- 18729108
TI  - Ligand-pKa shifts through metals: potential relevance to ribozyme chemistry.
AB  - Functional and crystallographic analyses of catalytically active RNA molecules
      ('ribozymes') have revealed a multitude of different routes by which nature
      accomplishes cleavage reactions of the RNA sugar-phosphate backbone. While there
      is agreement that these reactions involve general acid-base chemistry, the choice
      of 'acid' and of 'base' appears to be quite versatile. Among the numerous
      surprises that have emerged from these studies in recent years is the phenomenon
      of 'shifted pK(a) values' of nucleobases, hence, the fact that pK(a) values of
      isolated nucleobases in H(2)O can be shifted in either direction--upward or
      downward--into the physiological pH range, and that consequently allows these
      nucleobases to function as 'acids' or 'bases'. Another change in paradigm in
      recent years relates to the role of divalent metal ions in these catalytic
      reactions, which points to the possibility of an indirect involvement in the
      catalytic cycle rather than necessarily to a direct participation, as in the case
      with the hepatitis delta virus ribozyme. In this review, basic features of
      nucleobases and/or aqua ligand pK(a) shifts caused by metal coordination and H
      bonding are discussed.

PMID- 18729109
TI  - Vanadium detoxification: chemical and biochemical aspects.

PMID- 18729107
TI  - One heme, diverse functions: using biosynthetic myoglobin models to gain insights
      into heme-copper oxidases and nitric oxide reductases.

PMID- 18729110
TI  - Characterization of metal-responsive transcription factor (MTF-1) from the giant
      rodent capybara reveals features in common with human as well as with small
      rodents (mouse, rat). Short communication.
AB  - From mammals to insects, metal-responsive transcription factor 1 (MTF-1) is
      essential for the activation of metallothionein genes upon heavy-metal load. We
      have previously found that human MTF-1 induces a stronger metal response than
      mouse MTF-1. The latter differs from the human one in a number of amino acid
      positions and is also shorter by 78 aa at its C-terminus. We reasoned that the
      weaker metal inducibility might be associated with a lesser demand for tight
      metal homeostasis in a low-weight, short-lived animal, and thus set out to
      determine the sequence of MTF-1 from the largest living rodent, the Brazilian
      capybara that can reach 65 kg and also has a considerably longer life span than
      smaller rodents. An expression clone for capybara MTF-1 was then tested for its
      activity in both mouse and human cells. Our analysis revealed three unexpected
      features: i) capybara MTF-1 in terms of amino acid sequence is much more closely
      related to human than to mouse MTF-1, suggesting an accelerated evolution of MTF
      1 in the evolutionary branch leading to small rodents; ii) capybara MTF-1 is even
      32 aa shorter at its C-terminus than mouse MTF-1, and iii) in an activity test,
      it is not more active than mouse MTF-1. The latter two findings might indicate
      that capybara has evolved in an environment with low heavy-metal load.

PMID- 18729111
TI  - Metal-free and PdII-promoted [2+3] cycloadditions of a cyclic nitrone to
      phthalonitriles: syntheses of oxadiazolines as well as phthalamide-PdII and
      dihydropyrrolyl-iminoisoindolinone-PdII complexes with high catalytic activity in
      Suzuki-Miyaura cross-coupling reactions.
AB  - The previously unknown reactions between phthalonitriles, 1,2-(CN)2(C6)R1R2R3R4 1
      (1 a, R1=R2=R3=R4=H; 1 b, R1=R2=R4=H, R3=CH3; 1 c, R1=R4=H, R2=R3=Cl; 1 d,
      R1=R2=R3=R4=Cl; 1 e, R1=R2=R3=R4=F), and a cyclic nitrone, -O+N==CHCH2CH2CMe2 2,
      proceed under heating in a sealed tube to give phthalimides 3, 2-oxadiazolyl
      benzonitriles 4 or ortho-bis(oxadiazolyl)tetrafluorobenzene 4 e'. In the presence
      of palladium(II) chloride, phthalonitriles 1 react with 2 at room temperature, to
      give bis(pyrrolidin-2-ylidene)phthalamide PdII complexes 5 via metal-promoted
      rupture of the N--O bond of the oxadiazoline ring. The ketoimine ligands thus
      generated can be liberated from the metal by displacement with a diphosphine.
      Although the first [2+3] cycloaddition of 2 to 1 can occur in the absence of the
      metal to give the mono-cycloadducts 4, the second [2+3] coupling at the still
      unreacted cyano group requires its activation by coordination to PdII, affording
      complexes 6 containing two ligated oxadiazolyl-benzonitriles. These ligands
      undergo either i) further cycloaddition with 2 to afford ultimately (upon
      rearrangement) the bis(pyrrolidinylidene)phthalamide complexes 5 or ii) N--O bond
      cleavage in the oxadiazoline ring with intramolecular attack of the imine
      nitrogen on the cyano carbon and bridging to a second PdII center to afford
      dimeric palladium(II) complexes 7, with chloride bridges, that bear a
      dihydropyrrolyl-iminoisoindolinone, a new type of ligand.The compounds were
      characterized by IR, 1H, and 13C NMR spectroscopy, ESI MS or FAB+ MS, elemental
      analyses and, in the case of 4 c, 5 a, 5 c, and 7 c, also by X-ray diffraction
      analysis. Complexes 5 a and 7 c show high catalytic activity for the Suzuki
      Miyaura cross-coupling reaction of bromobenzene and phenylboronic acid and give
      biphenyl in high yields with turnover frequencies (TOFs) of up to 9.0x10(5) h(
      1).

PMID- 18729112
TI  - An unlockable-relockable iron cage by subcomponent self-assembly.

PMID- 18729113
TI  - Ferrimagnetic Heisenberg chains derived from [M(CN)8]3- (M=Mo(V), W(V)) building
      blocks.

PMID- 18729114
TI  - Strength enhancement of nanostructured organogels through inclusion of
      phthalocyanine-containing complementary organogelator structures and in situ
      cross-linking by click chemistry.
AB  - Stable photoactive organogels were successfully prepared by a two-step sequence
      involving: 1) formation of thermoreversible organogels by use of a combination of
      low-molecular-weight organogelators (LMOGs) and ZnII-phthalocyanine (ZnII-Pc)
      moieties containing complementary organogelator structures, and 2) strength
      enhancement of the gels by in situ cross-linking with the aid of CuI-catalysed
      azide-alkyne [3+2] cycloadditions (CuAACs). The optimum click reaction was
      carried out between a flexible C6 aliphatic diazide and a suitable dialkyne
      (molar ratio 1:1) added in a low proportion relative to the organogelator system
      [LMOG+ZnIIPc]. The dialkyne unit was incorporated into a molecule resembling the
      LMOGs structure in such a way that it could also participate in the self-assembly
      of [LMOG+ZnIIPc]. The significant compatibility of the multicomponent photoactive
      organogels towards this strengthening through CuAACs allowed their sol-to-gel
      transition temperatures (Tgel) to be enhanced by up to 15 degrees C. The Tgel
      values estimated by the "inverse flow method" were in good agreement with the
      values obtained by differential scanning calorimetry (DSC). Rheological
      measurements confirmed the viscoelastic, rigid, and brittle natures of all Pc
      containing gels. Transmission and scanning electron microscopy (TEM, SEM) and
      atomic force microscopy (AFM) revealed the fibrilar nature of the gels and the
      morphological changes upon cross-linking by CuAAC. Emission of a red luminescence
      from the dry nanoscale fibrous structure-due to the self-assembly of the Pc
      containing compounds in the organogel fibres-was directly observed by confocal
      laser scanning microscopy (CLSM). The optical properties were studied by UV/Vis
      and fluorescence spectroscopy. Fluorescence, Fourier-transform infrared (FTIR)
      and circular dichroism (CD) measurements were also carried out to complete the
      physicochemical characterization of selected gels. As a proof of concept, two
      different organogelators (cholesterol- and diamide-based LMOGs) were successfully
      used to validate the general strategy.

PMID- 18729115
TI  - Long-alkyl-chain quaternary ammonium lactate based ionic liquids.
AB  - A new group of quaternary ammonium lactate based ionic liquids have been prepared
      and characterized. Didecyldimethylammonium (DDA) and benzalkonium (BA) D,L- and L
      lactates are air-stable, hydrophilic, surface-active salts. They are very
      effective antibacterial and antifungal agents, especially the DDA lactates,
      against Streptococcus mutants and Candida albicans. Their activities are
      comparable or more effective than the original benzalkonium chloride. In
      addition, they have been shown to be good insect-feeding deterrents. However,
      they are poor antifungal agents for wood preservation. The toxicity of the DDA
      and BA lactates has also been studied and the results are presented in this
      paper.

PMID- 18729116
TI  - Enantioselective synthesis of [7]helicene: dramatic effects of olefin additives
      and aromatic solvents in asymmetric olefin metathesis.
AB  - The asymmetric synthesis of [7]helicene was accomplished in good ee (80%) by
      kinetic resolution by means of asymmetric olefin metathesis. Three key factors
      contributed to the success of the kinetic resolution: the use of new Ru-based
      olefin metathesis catalysts bearing C1-symmetric N-heterocyclic carbene ligands,
      simple olefins as additives to control the nature of the propagating alkylidene
      and hexafluorobenzene as a solvent.

PMID- 18729117
TI  - Rapid identification of common hexapyranose monosaccharide units by a simple
      TOCSY matching approach.
AB  - Solution NMR spectroscopy is a well established technique for non-destructive
      characterization of the structures and conformations of complex oligo- and
      polysaccharides. One of the key experiments involves the use of 2D TOCSY to
      collect the 1H spins into groups that can be associated with the individual
      saccharide units that are present in the molecule under study. It is well known
      that the magnetization transfer rate through the 1H spin system during the TOCSY
      spin lock period is sensitive to the intervening 3J(H,H) scalar couplings, and
      therefore also to the saccharide stereochemistry. Here, we have investigated the
      potential to extract information on the stereochemistry of hexapyranose
      monosaccharide units directly from TOCSY spectra. Through a systematic
      experimental investigation of the magnetization transfer initiated from the
      anomeric 1H resonance in D-glucose, D-galactose and D-mannose it is shown that a
      100 ms spin lock time provides optimal spectroscopic discrimination between these
      three commonly occurring building blocks. A simple matching scheme is proposed as
      a new tool for rapid attribution of the TOCSY traces originating from the
      anomeric 1H resonances towards the underlying monosaccharide type. The scheme
      appears robust with regard to structural variations and fairly tolerant to
      incidental overlap. Its application provides useful guidance during the
      subsequent NMR assignment process, as demonstrated with the PS7F polysaccharide
      from Streptococcus pneumonia. In addition, we show that our scheme affords a
      clear-cut distinction between the alpha- and beta-epimers of D-mannose-type
      units, which can be difficult to discriminate by NMR analysis. Application to the
      N-glycan 100.2 demonstrates the potential and wide applicability of this new
      discrimination approach.

PMID- 18729118
TI  - Heterogeneous gold catalysts for efficient access to functionalized lactones.
AB  - A novel class of heterogeneous gold catalysts supported on zeolite beta-NH4+ was
      prepared by the deposition-precipitation method. This new class of catalyst
      showed interesting catalytic activities for the intramolecular cycloisomerization
      of gamma-acetylenic carboxylic acids leading to functionalized gamma-alkylidene
      gamma-butyrolactones. Analysis of the supported gold species with in situ X-ray
      photoelectron spectroscopy (in situ XPS) suggests that cationic Au (possibly
      AuIII) can play an important role in such reactions. The high discrepancy in
      catalyst stability in favor of the Au supported on the zeolite system over bulk
      Au2O3 is explained by 1) the size of the particles and 2) the reversibility of
      the redox deactivating process (AuIII-->AuI) in the presence of oxygen for the
      supported system. The efficiency of this system allowed reaction under mild
      heterogeneous conditions. The potential for catalyst recycling was also
      highlighted.

PMID- 18729119
TI  - Fine-tunable organocatalysts bearing multiple hydrogen-bonding donors for
      construction of adjacent quaternary and tertiary stereocenters via a Michael
      reaction.

PMID- 18729120
TI  - Defective continuous hydrogen-bond networks: an alternative interpretation of IR
      spectroscopy.
AB  - We apply our previously developed deconvolution method and interpretation to
      analyze changes in the OH stretching band [nu(OH) band] of low-concentration (<
      or =0.2 m) aqueous solutions of NaCl and KCl. We treat these simple, monovalent
      ions as defects in the hydrogen-bond network of pure water and quantify the
      changes in the spectra at low defect concentration with an "order parameter".
      Order-parameter analysis of difference spectra of the two solutions leads to
      hydration numbers of 7.0+/-1.0 and 5.9+/-0.3 for K(+) and Na(+), respectively.
      Additionally, we find that changes in the nu(OH) band due to low concentrations
      of ions result from changes in the topology of the hydrogen-bond network.

PMID- 18729121
TI  - Quantitative property-activity relationship of PtRu/C catalysts for methanol
      oxidation.

PMID- 18729122
TI  - Ab initio studies on Li4+xTi5O12 compounds as anode materials for lithium-ion
      batteries.
AB  - The structural and electronic properties of Li(4+) (x)Ti(5)O(12) compounds (with
      0<or=x<or=6)-to be used as anode materials for lithium-ion batteries-are studied
      by means of first principles calculations. The results suggest that
      Li(4)Ti(5)O(12) can be lithiated to the state Li(8.5)Ti(5)O(12), which provides a
      theoretical capacity that is about 1.5 times higher than that of the compound
      lithiated to Li(7)Ti(5)O(12). Further insertion of lithium species into the
      Li(8.5)Ti(5)O(12) lattice results in a clear structural distortion. The small
      lattice expansion observed upon lithium insertion (about 0.4 % for the lithiated
      material Li(8.5)Ti(5)O(12)) and the retained [Li(1)Ti(5)](16d)O(12) framework
      indicate that the insertion/extraction process is reversible. Furthermore, the
      predicted intercalation potentials are 1.48 and 0.05 V (vs Li/Li(+)) for the
      Li(4)Ti(5)O(12)/Li(7)Ti(5)O(12) and Li(7)Ti(5)O(12)/Li(8.5)Ti(5)O(12) composition
      ranges, respectively. Electronic-structure analysis shows that the lithiated
      states Li(4+x)Ti(5)O(12) are metallic, which is indicative of good electronic
      conduction properties.

PMID- 18729123
TI  - Age of onset and death in inherited prion disease are heritable.
AB  - The common polymorphism at codon 129 of the prion protein gene (PRNP) is known to
      affect prion disease susceptibility, incubation period and phenotype. Mouse
      quantitative trait locus (QTL) studies demonstrate multiple modifiers of
      incubation time unlinked to Prnp, suggesting the existence of homologous human
      prion disease modifiers, but direct evidence of these has been lacking. We
      investigated the correlation of age at onset and death, expressed as a composite
      Z score, between parents and offspring in three large UK inherited prion disease
      kindreds. Our analysis suggests that overall heritability of the composite
      phenotype is 0.55 (95% CI 0.35-0.75). This measure may be an underestimate of the
      total genetic contribution to phenotypic heterogeneity as the analysis does not
      incorporate the effect of PRNP-linked modifiers. Although the confidence
      intervals are wide, these data suggest a significant heritable component to
      phenotypic variability and support attempts to identify human prion disease
      modifier genes which would be important in understanding the epidemiology of
      variant Creutzfeldt-Jakob disease (vCJD) in populations with significant exposure
      to bovine spongiform encephalopathy (BSE) prions.

PMID- 18729124
TI  - A germanate built from a 6(8)12(6) cavity cotemplated by an (H2O)16 cluster and 2
      methylpiperazine.

PMID- 18729125
TI  - Reversible optical sensor strip for oxygen.

PMID- 18729126
TI  - Multilateral solid-state metathesis reactions for the preparation of materials
      with heteroanions: the [Si(CN2)4]4- ion.

PMID- 18729127
TI  - An apoptosis-inducing small molecule that binds to heat shock protein 70.

PMID- 18729129
TI  - Weight limits, estimations of future BMI, subjective pubertal timing and physical
      appearance comparisons among adolescent girls as precursors of disturbed eating
      behaviour in a community sample.
AB  - OBJECTIVE: From a clinical point of view, a high 'objective' BMI or an early
      biological onset of puberty are well-known risk factors for eating disorders. In
      contrast, little is known about irrational beliefs and subjective meanings of
      body weight and pubertal timing. METHOD: Mostly using standardised
      questionnaires, 136 girls with an average age of 12 years were asked to report
      their eating behaviour, (body) self-esteem, body dissatisfaction, weight limits,
      estimations of future BMI, subjective pubertal timing and appearance-related
      social comparisons. RESULTS: Results showed significant correlations between
      disturbed eating behaviour and the existence of a weight limit, which was
      reported by 45% of the girls. Twenty two per cent wished to have a future BMI
      beneath the 10th percentile. In terms of pubertal timing, girls who perceived
      themselves as either 'early starters' or 'late starters' reported significantly
      more risky eating behaviour. CONCLUSIONS: Results are discussed with a focus on
      the psychotherapeutic use of our findings as well as the opportunity for the
      development of preventive strategies.

PMID- 18729128
TI  - The discovery of pyrano[3,4-b]indole-based allosteric inhibitors of HCV NS5B
      polymerase with in vivo activity.

PMID- 18729130
TI  - Cytochrome P450 2J2*7 polymorphisms in Japanese, Mongolians and Ovambos.
AB  - Human cytochrome P450 2J2 (CYP2J2) is abundant in cardiovascular tissue and
      active in the metabolism of arachidonic acid to eicosanoids that have potent
      vasodilatory properties. Variability of the CYP2J2 gene is highly constrained
      except for its proximal promoter: there is a relatively common and functionally
      relevant single nucleotide polymorphism, indicated by -50G > T polymorphism
      (CYP2J2*7). Although genetic variation is known among ethnic groups, data for
      allele frequency are limited to a few Caucasian, Asian, and one African
      populations. In the present study, genotype distribution of CYP2J2*7
      polymorphisms was investigated using polymerase chain reaction and restriction
      fragment length polymorphism assay in Japanese (n = 338), Mongolian (n = 118),
      and Ovambo (n = 186) populations and the findings compared with other
      populations. The mutant (CYP2J2*7) frequencies in the Japanese, Mongolians, and
      Ovambos were 0.0621, 0.0339, and 0.0672, respectively. Except for the Taiwanese,
      a general uniformity in the polymorphism in the Asian populations was observed.
      The mutation frequency of Ovambos was relatively lower than that of the African
      American population. This study is the first to investigate the distribution of
      the CYP2J2*7 gene polymorphisms in Japanese, Mongolians, and Ovambos. These data
      will be informative and facilitate genetic association studies, in Asian and
      African populations for CYP2J2-related diseases such as cardiovascular disorders.

PMID- 18729131
TI  - Learning experiences in dance class predict adult eating disturbance.
AB  - Elite dancers are at increased risk of eating disorders. The authors hypothesized
      that specific learning about thinness in dance class, rather than simple
      participation in dance training, tends to be an important aspect of the risk
      process. Approximately 500 college women reported on their previous dance
      experiences, their dance-related learning about thinness, their eating behaviours
      and attitudes and their thinness expectancies. Results showed that lifetime
      amount of time spent in dance class was unrelated to adult eating disturbance,
      women's reports of learning experiences concerning thinness during their dance
      classes predicted adult disordered eating concurrently, and thinness expectancies
      appeared to mediate the relationship between learning about thinness and adult
      eating disturbance. Learning experiences about thinness in dance class seem more
      important than time spent in dance class when examining the relationship between
      dance study and eating disorders.

PMID- 18729132
TI  - Loss of control over eating in overweight youngsters: the role of anxiety,
      depression and emotional eating.
AB  - The current study investigated loss of control (LC) over eating and the role of
      anxiety, depression and emotional eating in a sample of both treatment seeking (N
      = 115) and non-treatment seeking (N = 73) overweight youngsters (aged 8-18) using
      a semi-structured clinical interview and self-report questionnaires. It was found
      that treatment seekers reported twice as much LC (40%) compared to non-treatment
      seekers (21%). Cross-sectional prediction models indicated that increased anxiety
      was associated with emotional eating and LC. Emotional eating tended to mediate
      the relationship between anxiety and LC. Increased depression was associated with
      emotional eating but not with LC. Especially overweight treatment seekers turn
      out to be at risk for LC. Because LC may develop as a result of inadequate coping
      with negative emotions like anxiety, obesity treatment should focus on teaching
      more effective coping strategies. Longitudinal research is recommended to further
      elaborate affect regulation and LC.

PMID- 18729134
TI  - Regulatory expression of Brachyury and Goosecoid in P19 embryonal carcinoma
      cells.
AB  - Mouse P19 embryonal carcinoma cells can differentiate into various cell types
      depending on culture conditions. Here we show that the expression of the
      mesodermal genes Brachyury (Bra) and Goosecoid (Gsc) are under regulatory control
      in P19 cells. When P19 cells were cultured in a tissue culture dish in the
      presence of serum, Bra and Gsc were unexpectedly expressed. Expression of Bra and
      Gsc was greatly reduced with culture time, and expression levels at 144 h of
      culture were below 25% those at 48 h of culture. Members of the Tgf-beta family
      such as Activin and Nodal have been known to up-regulate expression of mesodermal
      genes. Treatment with SB431542, an Alk4/5/7 inhibitor, decreased Bra and Gsc in a
      dose-dependent manner, whereas it induced the expression of the neuroectodermal
      genes Mash-1 and Pax-6. Quantitative RT-PCR and dsRNAi transfection indicated
      Nodal as a possible ligand responsible for the regulation of Bra and Gsc. In
      addition, exogenous Nodal increased expression of Bra and Gsc in a dose-dependent
      manner. Serum concentration in culture medium positively related to expression of
      Nodal, Bra, Gsc, and Cripto, which encodes a membrane-tethered protein required
      for Nodal signaling. Addition of the culture supernatant of P19 cells at 144 h of
      culture to medium decreased expression of these genes. The present study reveals
      that stimulation and inhibition of the Nodal pathway increases mesodermal genes
      and neuroectodermal genes, respectively, indicating the importance of control of
      Nodal and Cripto expression for mesodermal formation and neurogenesis.

PMID- 18729136
TI  - Iatrogenic fetal membrane damage from complex fetoscopic surgery in human fetuses
      might not be amenable to simple closure by collagen plugs.

PMID- 18729135
TI  - A review and analysis of the relationship between neuropsychological measures and
      DAT1 in ADHD.
AB  - Meta-analyses indicate that the gene coding for the dopamine transporter (DAT1 or
      SLC6A3) is associated with an increased risk for ADHD. The mechanisms of this
      gene for ADHD are unclear. We systematically reviewed studies linking the VNTR in
      the 3' UTR of the DAT1 to neurophysiological and neuropsychological measures. In
      addition, a broad set of executive/cognitive and motor tests was administered to
      350 children (5-11 years) and adolescents (11-19 years) with ADHD and 195 non
      affected siblings. Two VNTRs (in intron 8 and the 3' UTR) and four SNPs (two 5'
      and two 3') in DAT1 were genotyped. The effect of the polymorphisms on
      neuropsychological functioning was studied. The review indicated that the
      majority of studies did not find a relation between DAT1 and neurophysiological
      or neuropsychological measures. In our sample, several of the polymorphisms of
      DAT1 were associated with ADHD and ADHD was associated with impaired
      neuropsychological functioning. However, none of the DAT1 polymorphisms was
      convincingly associated with neuropsychological dysfunctioning. This suggests
      that the effect of DAT1 on ADHD was not mediated by neuropsychological
      performance. However, since DAT1 is mainly expressed in the striatum and not the
      prefrontal cortex, it may influence striatum-related functions (such as delay
      aversion) more heavily than prefrontal related functions (such as executive
      functions). Associations of DAT1 with ADHD were only found in adolescents, which
      may suggest that DAT1 mainly exerts its effect in adolescence, and/or that having
      a more persistent form of ADHD may mark a more severe or homogeneous genetic form
      of the disorder.

PMID- 18729137
TI  - Who copes well? Obesity-related coping and its associations with shame, guilt,
      and weight loss.
AB  - The relationship among weight-related coping, guilt, and shame was investigated
      in a sample of 98 obese German individuals over a 6-month period. In terms of the
      objectives, the study explored the kind and frequency of typical coping
      situations in which obese individuals become aware of being obese. Furthermore,
      the study sought to determine the predictive utility of weight-related shame and
      guilt concerning coping responses, and to establish whether there is an
      association between coping responses and weight change. A longitudinal
      examination over a 6-month period was chosen with two measurement points. As
      typical distressing coping situations, individuals reported mostly negative
      evaluations through others/self, physical exercise situations, or environmental
      hazards (mainly shopping for clothes). Weight-related shame at baseline was a
      significant negative predictor for problem-focused engagement coping, whereas
      weight-related guilt was a significant positive predictor for problem-focused
      engagement strategies and dietary restraint at follow-up. Although Body Mass
      Index showed no substantial association with the coping measures, weight loss was
      accompanied by a substantial drop in problem-focused disengagement coping
      (wishful thinking, problem avoidance). Discussion of these findings focuses on
      the issue of possible effects of weight-related feelings of guilt and shame on
      coping behavior, the link between weight loss and disengaging coping strategies,
      and the possible use of the findings for cognitive-behavioral therapy for
      obesity.

PMID- 18729139
TI  - The tubulin polymerization promoting protein, TPPP/p25.

PMID- 18729145
TI  - Reducing anxiety sensitivity with exercise.
AB  - BACKGROUND: Exercise interventions repeatedly have been shown to be efficacious
      for the treatment of depression, and initial studies indicate similar efficacy
      for the treatment of anxiety conditions. To further study the potential
      beneficial role of prescriptive exercise for anxiety-related conditions, we
      examined the role of exercise in reducing fears of anxiety-related sensations
      (anxiety sensitivity). METHODS: We randomly assigned 60 participants with
      elevated levels of anxiety sensitivity to a 2-week exercise intervention, a 2
      week exercise plus cognitive restructuring intervention, or a waitlist control
      condition. Assessment of outcome was completed at pretreatment, midtreatment, 1
      week posttreatment, and 3-week follow-up. RESULTS: We found that both exercise
      conditions led to clinically significant changes in anxiety sensitivity that were
      superior to the waitlist condition, representing a large controlled effect size
      (d=2.15). Adding a cognitive component did not facilitate the effects of the
      exercise intervention. Consistent with hypotheses, changes in anxiety sensitivity
      mediated the beneficial effects of exercise on anxious and depressed mood.
      CONCLUSIONS: We discuss these findings in terms of the potential role of exercise
      as an additional psychosocial intervention for conditions such as panic disorder,
      where anxiety sensitivity is a prominent component of pathology.

PMID- 18729144
TI  - Predicting genetic loading from symptom patterns in obsessive- compulsive
      disorder: a latent variable analysis.
AB  - BACKGROUND: Some symptom dimensions in obsessive-compulsive disorder (OCD)
      patients have a familial and putative genetic foundation, based on replicated
      findings in studies of sib-pairs with OCD. However, these symptom dimensions are
      all from exploratory factor analyses of Yale-Brown Obsessive-Compulsive Scale
      Symptom Checklist ratings based on non-empirically derived symptom categories,
      rather than individual symptoms. METHODS: In this study, we used a novel latent
      variable mixture model analysis to identify meaningful patient subgroupings. This
      was preceded by a confirmatory factor analysis of a 65-item OCD symptom inventory
      from 398 OCD probands, which yielded a five-factor solution. Data from all five
      symptom factors were used in a latent variable mixture model analysis, which
      identified two statistically separate OCD subpopulations. RESULTS: One group of
      probands had a significantly higher proportion of OCD-affected afflicted
      relatives (parents or close parental relatives), whereas the other group had a
      less prevalent familial OCD. The group with the more familial OCD was also found
      to have an earlier age of OCD onset, more severe OCD symptoms, and greater
      psychiatric comorbidity and impairment. CONCLUSIONS: Especially if the results
      are verified in other samples, this research paradigm, which identified
      characteristics of individuals with familial OCD, should prove useful in carrying
      out genome-wide linkage and association studies of OCD and may provide a model
      for other symptom-based studies of additional medical disorders.

PMID- 18729146
TI  - Trauma exposure and posttraumatic reactions in a community sample of Bedouin
      members of the Israel Defense Forces.
AB  - BACKGROUND: Limited available data indicate that minorities in military service
      face heightened risks for traumatic exposure and more severe posttraumatic
      reactions. This study explored traumatic exposure and impact on mental and
      physical health, functioning, and medical services utilization in a previously
      unstudied ethnic minority group of Bedouins enlisted in the Israeli Defense
      Forces. METHODS: Participants were 317 community-based Bedouin servicemen
      recruited through community outreach efforts. Axis I psychiatric diagnoses were
      determined by the Structured Clinical Interview for DSM-IV Disorders;
      posttraumatic symptoms were measured with the Screen for Posttraumatic Stress
      Symptoms; and depression and anxiety symptoms were assessed by the Hopkins
      Symptom Checklist -25 (HSCL-25) Arabic version. Functional impairment and health
      service utilization were measured by a self-report questionnaire. RESULTS: Use of
      a stringent definition of trauma, restricted to experiences involving physical
      presence at the scene of the event, revealed that 75% of respondents reported
      potentially traumatizing events. Cap of these nearly 20% were diagnosed with
      posttraumatic stress disorder (PTSD), which was mostly co-morbid with depression,
      alcohol abuse, or both. In spite of the widespread trauma exposure in this
      community, only those trauma-exposed men who developed PTSD experienced extensive
      impact on their health, as indicated by associations with poor health status,
      physician-diagnosed medical conditions, health-related impairment in daily
      functioning, and frequent use of primary or specialty care services. Mental
      health services were typically not utilized. CONCLUSIONS: Detection of PTSD among
      Bedouin servicemen necessitates deliberate diagnostic efforts within primary care
      settings.

PMID- 18729147
TI  - Treating university students with social phobia and public speaking fears:
      Internet delivered self-help with or without live group exposure sessions.
AB  - BACKGROUND: This study investigated the efficacy of an Internet-based self-help
      program with minimal therapist contact via e-mail for Swedish university students
      with social phobia and public speaking fears. The main objective was to test if
      the Internet-based self-help program would be more effective if five live group
      exposure sessions were added. METHODS: Thirty-eight students meeting the
      diagnostic and statistical manual of mental disorders, 4th edition criteria for
      social phobia were randomized into two different treatment groups: Internet
      delivered cognitive behavior therapy combined with five group exposure sessions
      (ICBT+ exp) or the Internet program alone (ICBT). RESULTS: Results were analyzed
      on an intention-to-treat basis. Both treatment groups showed significant
      improvement from pre- to post-test, and from pre-test to 1-year follow-up, on all
      measured dimensions (social anxiety, general anxiety, depression levels, and
      quality of life). For both the groups, the average within-group effect sizes for
      the primary social anxiety scales, expressed as Cohen's d, were comparable to
      those seen in traditionally administered cognitive behavioral therapy both at
      post-test and at 1- year follow-up. CONCLUSIONS: The results suggest that the
      Internet-based self-help program on its own is efficient in the treatment of
      university students with social phobia. Adding group exposure sessions did not
      improve the outcome significantly.

PMID- 18729149
TI  - Measures matter: the relative contribution of anxiety and depression to suicidal
      ideation in clinically referred anxious youth using brief versus full length
      questionnaires.
AB  - BACKGROUND: A cross-sectional design was used to examine links between suicidal
      ideation, depression, and anxiety using brief [Stark and Laurent, 2001: J Clin
      Child Psychol 30:552-567] and full length versions of the Children's Depression
      Inventory [CDI; Kovacs, 1980/1981: Acta Paedopsychiatr 46:305-315] and Revised
      Children's Manifest Anxiety Scale [RCMAS; Reynolds and Richmond, 1985: Revised
      Children's Manifest Anxiety Scale. California: Western Psychological Services].
      METHODS: The sample consisted of 252 children and adolescents (ages 7-16 years,
      M=9.94 years (SD=2.4)) seeking treatment at a childhood anxiety disorders
      specialty research clinic. RESULTS: Using structural equation modeling, results
      indicated that the relative contribution of anxiety and depression in the
      presence of suicidal ideation varies depending on the measures used.
      Specifically, anxiety had a significant direct and indirect effect on suicidal
      ideation presence using a brief version of the RCMAS, but only an indirect effect
      using the full length version. Depression had a significant direct effect on
      suicidal ideation presence using both brief and full versions of the CDI.
      CONCLUSIONS: These findings suggest that anxiety may play a role in predicting
      suicidal ideation in clinic-referred anxious youth, but whether this role is
      detected depends on the measurement strategy. Given that "measures matter,"
      future studies using similar as well as different samples as the one used in this
      study need to consider careful measurement strategies, as different findings may
      emerge depending on whether brief or full length versions of questionnaires are
      used.

PMID- 18729148
TI  - A multirisk approach to predicting chronicity of postpartum depression symptoms.
AB  - BACKGROUND: Persistence of postpartum depression (PPD) carries potential adverse
      implications for the emerging mother-child relationship and for child
      development. METHODS: This study was designed to investigate factors related to
      the onset and persistence of PPD; in particular, we examined the cumulative
      effect of a range of psychosocial risk factors in predicting chronic PPD
      symptoms. One hundred and five women were interviewed at three assessment
      periods: within the first days after childbirth, at 6 months, and at 18 months
      postpartum. RESULTS: Depressive symptoms at 6 months predicted 18 months
      depressive symptoms, even when controlling for the contribution of maternal
      depression at birth. Psychosocial risk had a moderating influence on the
      stability of depressive symptomatology. Women with two or more risk factors at
      birth were more likely to have stable depressive symptomatology across the
      infants' first 18 months of life. CONCLUSION: To prevent a chronic course of PPD
      it may be necessary to identify both depressive symptoms and relevant
      psychosocial risk factors.

PMID- 18729150
TI  - Developmental and spatial expression pattern of alpha-taxilin in the rat central
      nervous system.
AB  - Alpha-taxilin has been identified as a binding partner of syntaxin family members
      and thus has been proposed to function in syntaxin-mediated intracellular vesicle
      trafficking. However, the lack of detailed information concerning the cellular
      and subcellular localization of alpha-taxilin impedes an understanding of the
      role of this protein. In the present study, we characterized alpha-taxilin
      expressing cells in the rat CNS with a specific antibody. During embryonic
      development, alpha-taxilin was prominently expressed in nestin-positive neural
      stem cells in vivo and in vitro. As CNS development proceeded, the alpha-taxilin
      expression level was rapidly down-regulated. In the postnatal CNS, alpha-taxilin
      expression was almost confined to the neuronal lineage, with the highest levels
      of expression in motor neurons within the brainstem nuclei and spinal cord and in
      primary sensory neurons in mesencephalic trigeminal nucleus. At the cellular
      level, alpha-taxilin was preferentially located in Nissl substance-like
      structures with a tigroid or globular morphology within the soma and proximal to
      dendrites, but it was excluded from terminals. Combined staining with propidium
      iodide demonstrated that alpha-taxilin distribution overlapped with the
      cytoplasmic compartment enriched in RNA species, suggesting a close association
      of alpha-taxilin with actively translating ribosomes or polysomes in neurons. In
      agreement with this, a recent study indicated the preferential binding of alpha
      taxilin to the nascent polypeptide-associated complex (alphaNAC), a dynamic
      component of the ribosomal exit tunnel in eukaryotic cells. Taken together, these
      findings suggest that alpha-taxilin plays multiple roles in the generation and
      maintenance of neurons through modulation of the NAC-mediated translational
      machinary and/or the syntaxin-mediated vesicle traffic in the soma.

PMID- 18729151
TI  - Carotid angioplasty and stenting in octogenarians: is it safe?
AB  - PURPOSE: Elderly patients have a higher risk of complications in carotid
      endarterectomy. The aim of the study was to evaluate whether carotid artery
      stenting (CAS) performed in octogenarians also increases the procedure related
      risk. METHODS: 870 patients (male 626) mean age 70.9 +/- 9.3 years underwent 930
      CAS for de novo lesions (n = 851) restenoses (n = 54) post radiation (n = 14)
      inflammatory arteritis (n = 9) post trauma aneurysms (n = 2). Indications for
      treatment: symptomatic carotid stenosis > or = 70% (n = 577) or asymptomatic
      stenosis > or = 80%. Patients were separated into two age groups: <80 years (749
      patients, 806 CAS) and >80 years (121 patients, 124 CAS). 187 CAS performed
      without protection (N.P-) 6 patients >80 years, 743 with protection (NP+)
      (occlusion balloon: 334, filters: 404, reversal flow: 6) 118 patients >80 years.
      Data analysis included neurological complications, death and myocardial
      infarction (MI) rate at 30 days, anatomical particularities. Technical points
      will be described depending on the age of the patient. RESULTS: Technical success
      804/806 in patients <80 years, 123/124 in patients >80 years (NS). 30 days
      outcomes: in the patient group <80 years we observed 9 TIA (1.1%) 3 without NP
      (1.7%) 6 with NP (0.9%), 5 minor strokes (0.6%) 2 without NP (1.1%) 3 with NP
      (0.5%), 3 major strokes: 2 without NP (1.1%) 1 with NP (0.2%), 5 deaths (0.6%) 2
      without NP (1.1%) 3 with NP (0.5%). Death/stroke/MI: 14 (1.8%) 6 without NP
      (3.3%), 8 with NP (1.3%). In the group >80 years, we observed 2 TIA (1.7%) 1
      without NP 1 with NP (0.92%) 1 minor stroke without NP (17%) no major stroke, no
      death. Death/stroke/MI 1 without NP (17%). CONCLUSION: CAS can be performed in
      elderly patients without higher risk than in younger patients. But good
      indications, a meticulous technique, protection devices are mandatory and some
      technical points must be pointed out to avoid neurological complications and
      failures.

PMID- 18729152
TI  - Pleural effusion due to intra-abdominal extravasation of parenteral nutrition.
AB  - An 8-week-old preterm boy experienced respiratory deterioration due to unilateral
      pleural effusion. Intra-abdominal extravasation of parenteral fluid with leakage
      into the pleural cavity was suspected based on biochemical analysis of the
      effluent. Perforation of the central venous catheter in the peritoneal cavity was
      subsequently confirmed by contrast roentgenography. As in peritoneal dialysis and
      hepatic hydrothorax, pleuroperitoneal communication needs to be considered in
      patients exhibiting pleural effusion with a central venous line below the
      diaphragm.

PMID- 18729153
TI  - The matter at hand.

PMID- 18729154
TI  - Neuroanatomy of the complex tibial organ of Stenopelmatus (Orthoptera: Ensifera:
      Stenopelmatidae).
AB  - Stenopelmatidae (or "Jerusalem crickets") belong to the atympanate Ensifera,
      lacking hearing organs in the foreleg tibiae. Their phylogenetic position is
      controversial, either as a taxon in Tettigonioidea or within the clade of
      Gryllacridoidea. Similarly, the origin of tibial auditory systems in Ensifera is
      controversial. Therefore, we investigated the neuronal structures of the proximal
      tibiae of Stenopelmatus spec. with the hypothesis that internal sensory
      structures are similar to those in tympanate Ensifera. In Stenopelmatus the
      complex tibial organ consists of three neuronal parts: the subgenual organ, the
      intermediate organ, and a third part with linearly arranged neurons. This
      tripartite organization is also found in tympanate Ensifera, verifying our
      hypothesis. The third part of the sense organ found in Stenopelmatus can be
      regarded by the criterion of position as homologous to auditory receptors of
      hearing Tettigonioidea. This crista acustica homolog is found serially in all
      thoracic leg pairs and contains 20 +/- 2 chordotonal neurons in the foreleg. The
      tibial organ was shown to be responsive to vibration, with a broad threshold of
      about 0.06 ms(-2) in a frequency range from 100-600 Hz. The central projection of
      tibial sensory neurons terminates into two equally sized lobes in the primary
      sensory neuropil, the medial ventral association center. The data are discussed
      comparatively to those of other Ensifera and mapped phylogenetically onto
      recently proposed phylogenies for Ensifera. The crista acustica homolog could
      represent a neuronal rudiment of a secondarily reduced ear, but neuronal features
      are also consistent with an evolutionary preadaptation.

PMID- 18729155
TI  - Type 1 diabetes mellitus: primary, secondary, and tertiary prevention.
AB  - We have entered the era of clinical trials to prevent type 1 diabetes mellitus
      (T1DM). Before 1922, when insulin was first given to a patient with diabetes, a
      diagnosis of T1DM was considered a death sentence. Advances in treatment for
      subjects with diabetes are not yet sufficient to prevent the deleterious impact
      of diabetes on both day-to-day activities and the early morbidity and mortality
      still associated with the disease. We now understand a great deal about blood
      glucose regulation and potential health complications associated with long-term
      T1DM, but the mystery of why, or the pathogenesis of this devastating disease,
      remains elusive. Great strides toward unraveling this mystery have been made over
      the past several decades. Even without definitive answers, we are moving from the
      period of discovery and animal research to the era of clinical trials. In this
      review, we wish to convey the palpable excitement in the field. It is time to
      determine if we can safely change the course of T1DM.

PMID- 18729156
TI  - Kidney and pancreas transplantation in type 1 diabetes mellitus.
AB  - Type 1 diabetes mellitus is characterized by autoimmune destruction of pancreatic
      beta cells, leading to a state of absolute insulin deficiency. Glycemic control
      via the use of exogenous insulin injections is often imperfect, resulting in
      multiple long-term complications, such as retinopathy, neuropathy, vasculopathy,
      and nephropathy. The Diabetes Control and Complications Trial has provided
      conclusive evidence that better glycemic control by intensive insulin treatment
      effectively delays the onset and slows the progression of diabetic retinopathy,
      nephropathy, and neuropathy in patients with insulin-dependent diabetes mellitus.
      At this moment, the only reliable option for achieving long-term insulin
      independence is whole-pancreas transplantation. The proposed benefits of pancreas
      transplantation are clear: improved quality of life, prevention of recurrent
      diabetic nephropathy, freedom from exogenous insulin with euglycemia and
      normalization of glycosylated hemoglobin, less stringent dietary restrictions,
      less frequent blood glucose monitoring, and stabilization of or improvement in
      secondary complications. The trade-offs to the patient are the operative risk,
      the need for chronic immunosuppression, and the inherent side effects of chronic
      immunosuppression.

PMID- 18729157
TI  - Contemporary issues in management of carotid occlusive disease.

PMID- 18729158
TI  - EBM on call: management of minimally symptomatic inguinal hernia.

PMID- 18729159
TI  - Hepatitis C: current and future therapies.

PMID- 18729168
TI  - Abstracts of the 133rd Annual Meeting of the American Neurological Association.
      September 21-24, 2008. Salt Lake City, Utah, USA.

PMID- 18729170
TI  - Through the back door - retrograde stenting in chronic total occlusions.

PMID- 18729171
TI  - The roads less traveled.

PMID- 18729172
TI  - Liar, liar, pants on fire.

PMID- 18729173
TI  - Transient and persistent renal dysfunction are predictors of survival after
      percutaneous coronary intervention: insights from the Dartmouth Dynamic Registry.
AB  - OBJECTIVES: We sought to determine if transient and persistent elevations in
      creatinine following percutaneous coronary intervention (PCI) resulted in poor
      survival. BACKGROUND: Limited survival data exist that defines the natural
      survival history of transient and persistent renal dysfunction following
      interventional PCI cases. METHODS: Data were collected prospectively on 7,856
      consecutive patients undergoing PCI from January 1, 2000 to July 31, 2006. Ninety
      three patients were excluded due to pre-PCI dialysis. Patients were stratified
      into three categories of renal dysfunction: no renal dysfunction from baseline
      (<0.5 mg/dL increase in creatinine within 48 hr of the procedure), transient
      renal dysfunction (> or =0.5 mg/dL increase in creatinine within 48 hr with
      return to normal within 2 weeks), and persistent renal dysfunction (> or =0.5
      mg/dL increase in creatinine without returning to normal within 2 weeks of the
      procedure). Mortality was determined by comparing with the Social Security Death
      Master File. RESULTS: Median survival was 3.2 years (mean 3.4). Renal dysfunction
      occurred in 250 patients (0.5 mg/dL increase in creatinine). Survival was
      significantly different between patients at 1, 3.2, and 7.5 years (P-value <
      0.001): no renal dysfunction (95%, 88%, 75%), with transient (61%, 42%, 0%), and
      with persistent (58%, 44%, 36%) renal dysfunction. Patients with transient or
      persistent renal dysfunction had a twofold-threefold increased risk of 7.5-year
      mortality compared with patients with no renal dysfunction. CONCLUSIONS: Both
      transient and persistent postprocedural renal dysfunction are prognostically
      significant for mortality during extended follow-up. Renal dysfunction should be
      closely monitored before and after PCI.

PMID- 18729174
TI  - Advancing backward: a word of caution.

PMID- 18729175
TI  - Recognizing and reducing the cardiac risk of renal failure.

PMID- 18729177
TI  - Type 1 diabetes mellitus: new knowledge of etiology, new approaches to
      management.

PMID- 18729178
TI  - Immunology and genetics of type 1 diabetes.
AB  - Type 1 diabetes is one of the most well-characterized autoimmune diseases. Type 1
      diabetes compromises an individual's insulin production through the autoimmune
      destruction of pancreatic beta-cells. Although much is understood about the
      mechanisms of this disease, multiple potential contributing factors are thought
      to play distinct parts in triggering type 1 diabetes. The immunological diagnosis
      of type 1 diabetes relies primarily on the detection of autoantibodies against
      islet antigens in the serum of type 1 diabetes mellitus patients. Genetic
      analyses of type 1 diabetes have linked human leukocyte antigen, specifically
      class II alleles, to susceptibility to disease onset. Environmental catalysts
      include various possible factors, such as viral infections, although the evidence
      linking infections with type 1 diabetes remains inconclusive. Imbalances within
      the immune system's system of checks and balances may promote immune activation,
      while undermining immune regulation. A lack of proper regulation and overactive
      pathogenic responses provide a framework for the development of autoimmune
      abnormalities. Type 1 diabetes is a predictable and potentially treatable disease
      that still requires much research to fully understand and pinpoint the exact
      triggering events leading to autoimmune activation. In silico research can aid
      the comprehension of the etiology of complex disease pathways, including Type I
      diabetes, in order to and help predict the outcome of therapeutic strategies
      aimed at preserving beta-cell function.

PMID- 18729176
TI  - Ultrastructural analysis of the cristae ampullares in the squirrel monkey
      (Saimiri sciureus).
AB  - Type I hair cells outnumber type II hair cells (HCs) in squirrel monkey (Saimiri
      sciureus) cristae by a nearly 3:1 ratio. Associated with this type I HC
      preponderance, calyx fibers make up a much larger fraction of the afferent
      innervation than in rodents (Fernandez et al. [1995] J. Neurophysiol. 73:1253
      1269). To study how this affects synaptic architecture, we used disector methods
      to estimate various features associated with type I and type II HCs in central
      (CZ) and peripheral (PZ) zones of monkey cristae. Each type I HC makes, on
      average, 5-10 ribbon synapses with the inner face of a calyx ending. Inner-face
      synapses outnumber those on calyx outer faces by a 40:1 ratio. Expressed per
      afferent, there are, on average, 15 inner-face ribbon synapses, 0.38 outer-face
      ribbons, and 2.6 efferent boutons on calyx-bearing endings. Calyceal
      invaginations per type I HC range from 19 in CZ to 3 in PZ. For type II HCs,
      there are many more ribbons and afferent boutons in PZ than in CZ, whereas
      efferent innervation is relatively uniform throughout the neuroepithelium.
      Despite outer-face ribbons being more numerous in chinchilla than in squirrel
      monkey, afferent discharge properties are similar (Lysakowski et al. [1995] J.
      Neurophysiol. 73:1270-1281), reinforcing the importance of inner-face ribbons in
      synaptic transmission. Comparisons across mammalian species suggest that the
      prevalence of type I HCs is a primate characteristic, rather than an arboreal
      life-style adaptation. Unlike cristae, type II HCs predominate in monkey maculae.
      Differences in hair-cell counts may reflect the stimulus magnitudes handled by
      semicircular canals and otolith organs.

PMID- 18729179
TI  - Complications of type 1 diabetes: new molecular findings.
AB  - Interventions targeting the treatment of diabetic complications have not been
      nearly as successful as initially estimated, despite a marked improvement in
      therapeutic options for diabetes. The need for understanding why some very
      promising interventions have failed demands a closer look at the pathomechanisms
      of the complications. Great strides have been made in understanding the
      pathology, and several important hypotheses have emerged in recent years. On this
      basis, Brownlee and coworkers suggested a unifying hypothesis integrating various
      mechanisms discussed in past years with an overproduction of reactive oxygen
      species as an initiating cause. This hypothesis and further hypotheses, as well
      as mechanisms, are highlighted in this article. The field of pathomechanisms of
      diabetic complications is very wide, and any attempt to completely cover it
      within a single article is unrealistic. Therefore, our purpose is to present the
      most relevant concepts underlying diabetic complications in an attempt to
      contribute to a better understanding and pinpoint areas that warrant further
      research.

PMID- 18729181
TI  - Toward a cell-based cure for diabetes: advances in production and transplant of
      beta cells.
AB  - Type 1 diabetes results from autoimmune destruction of the insulin-producing beta
      cells of the pancreatic islets of Langerhans. Although developments in exogenous
      insulin therapy have greatly improved clinical outcomes in patients with
      diabetes, the ability of the pancreatic beta cell to exquisitely regulate the
      delivery of insulin and maintain normal levels of blood glucose is still far
      superior to what can be achieved by external delivery of insulin. As a result,
      the majority of patients with type 1 diabetes still experience the complications
      of chronic hyperglycemia or serious and potentially life-threatening
      hypoglycemia. The shortcomings of medical therapy have driven research toward
      more direct approaches of beta cell replacement. Indeed, the specificity of beta
      cell loss in type 1 diabetes makes this disease a particularly attractive
      candidate for cell-based therapies. In order for significant progress to be made,
      however, a thorough understanding of beta cell biology and more broadly islet
      biology is necessary. This review addresses recent advances in developmental
      biology that have expanded our understanding of islet cell differentiation,
      assesses the promise and limitations of islet transplantation, and discusses the
      future of alternative sources of beta cells, including directed differentiation
      of stem cells, replication of adult beta cells, and transdifferentiation of
      nonislet cells to a beta cell fate. =

PMID- 18729180
TI  - Past, present, and future of insulin pump therapy: better shot at diabetes
      control.
AB  - With the advent of continuous subcutaneous insulin infusion therapy and the
      findings of the Diabetes Control and Complications Trial, the management of type
      1 diabetes has changed drastically. Over the past 30 years since its development,
      the effectiveness of continuous subcutaneous insulin infusion has been assessed
      in comparison with other modes of intensive treatment. Additionally, improvements
      in pump delivery systems have been made. Here, the findings of the studies on
      pump therapy are reviewed. Selection criteria of patients for pump use and how to
      initiate pump therapy are presented. Finally, newer findings on continuous
      glucose sensors are discussed as the next era of pump therapy continues to focus
      on the goal of developing an artificial pancreas.

PMID- 18729182
TI  - Targeting the methionine cycle for melanoma therapy with 3-O-(3,4,5
      trimethoxybenzoyl)-(-)-epicatechin.
AB  - The higher expression of methionine cycle genes in melanoma cells than in normal
      melanocytes may be related with increased protein synthesis and transmethylation
      reactions and the subsequent need for high levels of methionine. 3-O-(3,4,5
      trimethoxybenzoyl)-(-)-epicatechin (TMECG), a trimethoxy derivative of
      epicatechin-3-gallate (ECG), effectively suppressed proliferation of melanoma
      cells in cultures by inducing apoptosis. TMECG modulates the expression of genes
      involved in methionine metabolism, cellular methylation and glutathione synthesis
      in melanoma cells. TMECG treatment of melanoma cells resulted in the
      downregulation of antiapoptotic Bcl-2, the upregulation of proapoptotic Bax and
      the activation of caspase-3; however, it did not induce the expression of the
      apoptosis protease-activating factor-1 (Apaf-1). Having elucidated the effects of
      TMECG on the melanoma methionine cycle, we designed therapeuthical strategies to
      increase its effectiveness. Combinations of TMECG with S-adenosylmethionine or
      compounds that modulate the intracellular concentration of adenosine strongly
      increase the antiproliferative effects of TMECG. The ability of TMECG to target
      multiple aspects related with melanoma survival, with a high degree of potency,
      points to its clinical value in melanoma therapy.

PMID- 18729183
TI  - Risk of second primary cancer among patients with head and neck cancers: A pooled
      analysis of 13 cancer registries.
AB  - The objective of the study was to assess the risk of second primary cancers
      (SPCs) following a primary head and neck cancer (oral cavity, pharynx and larynx)
      and the risk of head and neck cancer as a SPC. The present investigation is a
      multicenter study from 13 population-based cancer registries. The study
      population involved 99,257 patients with a first primary head and neck cancer and
      contributed 489,855 person-years of follow-up. To assess the excess risk of SPCs
      following head and neck cancers, we calculated standardized incidence ratios
      (SIRs) by dividing the observed numbers of SPCs by the expected number of cancers
      calculated from accumulated person-years and the age-, sex- and calendar period
      specific first primary cancer incidence rates in each of the cancer registries.
      During the observation period, there were 10,826 cases of SPCs after head and
      neck cancer. For all cancer sites combined, the SIR of SPCs was 1.86 (95% CI =
      1.83-1.90) and the 20-year cumulative risk was 36%. Lung cancer contributed to
      the highest proportion of the SPCs with a 20-year cumulative risk of 13%. Excess
      second head and neck cancer risk was observed 10 years after diagnosis with
      lymphohaematopoietic cancers. The most common SPC following a first primary head
      and neck cancer was lung cancer. However, the highest excess of SPCs was in the
      head and neck region. These patterns were consistent with the notion that the
      pattern of cancer in survivors of head and neck cancer is dominated by the effect
      of tobacco smoking and alcohol drinking.

PMID- 18729184
TI  - Prognostic evaluation of epidermal fatty acid-binding protein and calcyphosine,
      two proteins implicated in endometrial cancer using a proteomic approach.
AB  - With the aim to translate the discovery from proteomic research into clinical
      applications, we identified epidermal fatty acid-binding protein (E-FABP) and
      calcyphosine (CAPS) by MALDI-Q-TOF MS and validated their overexpressions by
      immunoblotting. Their expression statuses were examined by immunohistochemistry
      in 39 normal endometrium, 29 endometrial intraepithelial neoplasia (EIN) and 84
      endometrial cancer (EC) cases. We evaluated the correlations to the
      clinicopathologic characteristics and determined whether these proteins had
      prognostic significance. Expressions of E-FABP and CAPS were increased 2.64- and
      2.18-fold in EC by immunoblotting. Immunoreactivity of both E-FABP and CAPS were
      stronger in EC than in EIN or normal tissues (p < 0.001 and < 0.001). Stronger
      immunoreactivity of E-FABP and CAPS were shown to present with poor
      differentiation (p = 0.032 and 0.001), but no relevance was observed with staging
      (p = 1.368 and 4.306). Survival analysis indicated that immunoreactivity of CAPS
      was correlated to poor survival (p = 0.018), but E-FABP status appeared to be no
      correlation to the clinical outcome of patients (p = 0.865). Multivariate
      analysis indicated that CAPS might be an independent prognostic factor for
      survival in patients with EC (p = 0.008). Results demonstrated the ubiquitous
      overexpressions of E-FABP and CAPS in EC and the correlations to the
      clinicopathologic parameters. CAPS might be a potential prognostic factor for
      survival in patients with EC. The research pattern from proteomics to clinical
      specimens would have widespread applications.

PMID- 18729187
TI  - A polygenic model with common variants may predict lung adenocarcinoma risk in
      humans.
AB  - Genome-wide screening for genetic loci associated with risk of lung
      adenocarcinoma (ADCA) was carried out in pooled DNA using the Illumina 300K
      single-nucleotide polymorphism (SNP) array, in a joint analysis of 2 Italian case
      control series matched by age, gender and smoking habit. The rare allele carrier
      status of 8 SNPs was associated with a decreased lung ADCA risk [odds ratios
      (OR): 0.6-0.8]. In a polygenic model characterized by additive and
      interchangeable effects, individuals carrying 2 to 6 rare alleles at these 8 SNPs
      showed a significant trend toward a decreased risk of lung ADCA (up to OR of
      0.3). These results suggest the relevance of a polygenic model in the modulation
      of individual risk of lung ADCA in the general population.

PMID- 18729185
TI  - Tumor expressed PTHrP facilitates prostate cancer-induced osteoblastic lesions.
AB  - Expression of parathyroid hormone-related protein (PTHrP) correlates with
      prostate cancer skeletal progression; however, the impact of prostate cancer
      derived PTHrP on the microenvironment and osteoblastic lesions in skeletal
      metastasis has not been completely elucidated. In this study, PTHrP
      overexpressing prostate cancer clones were stably established by transfection of
      full length rat PTHrP cDNA. Expression and secretion of PTHrP were verified by
      western blotting and IRMA assay. PTHrP overexpressing prostate cancer cells had
      higher growth rates in vitro, and generated larger tumors when inoculated
      subcutaneously into athymic mice. The impact of tumor-derived PTHrP on bone was
      investigated using a vossicle co-implant model. Histology revealed increased bone
      mass adjacent to PTHrP overexpressing tumor foci, with increased
      osteoblastogenesis, osteoclastogenesis and angiogenesis. In vitro analysis
      demonstrated pro-osteoclastic and pro-osteoblastic effects of PTHrP. PTHrP
      enhanced proliferation of bone marrow stromal cells and early osteoblast
      differentiation. PTHrP exerted a pro-angiogenic effect indirectly, as it
      increased angiogenesis but only in the presence of bone marrow stromal cells.
      These data suggest PTHrP plays a role in tumorigenesis in prostate cancer, and
      that PTHrP is a key mediator for communication and interactions between prostate
      cancer and the bone microenvironment. Prostate cancer-derived PTHrP is actively
      involved in osteoblastic skeletal progression.

PMID- 18729188
TI  - Measures of cutaneous human papillomavirus infection in normal tissues as
      biomarkers of HPV in corresponding nonmelanoma skin cancers.
AB  - Cutaneous human papillomavirus (HPV) may be associated with the development of
      nonmelanoma skin cancer (NMSC), as suggested by reports of HPV DNA in NMSC
      tumors. HPV has also been investigated as an NMSC risk factor in epidemiologic
      studies, although findings vary across studies that used different biomarkers of
      HPV infection in normal tissues. To identify appropriate biomarkers for use in
      future epidemiologic studies, we conducted a sampling validation study. NMSC
      tumor tissue was obtained from 20 patients with pathology-confirmed basal or
      squamous cell carcinoma of the skin, in addition to several normal tissues,
      including eyebrow hairs, normal skin swabs obtained using multiple techniques,
      normal skin punch and shave biopsies, and serum for antibody measurement.
      Presence of cutaneous HPV DNA in tissues was measured with multiplex PCR using
      HPV type-specific primers and array primer extension (APEX) for HPV typing.
      Antibody detection was based on glutathione-S-transferase capture ELISA in
      combination with fluorescent bead technology. Using HPV DNA in tumor tissues as a
      gold standard, sensitivity and specificity were calculated for each measure of
      HPV infection in normal tissues. beta-Papillomavirus DNA was observed in tumor
      tissues in 60% of patients. The normal skin punch biopsy demonstrated optimal
      sensitivity (75%) and specificity (75%). Biomarkers obtained using less-invasive
      techniques demonstrated poor specificity when considered individually, although
      specificity improved when biomarkers were combined. Based on the current case
      series, the combinations of antibodies+eyebrow hairs or antibodies+eyebrow
      hairs+Dacron swabs are the optimal, minimally invasive markers of cutaneous HPV
      infection for use in epidemiologic studies.

PMID- 18729189
TI  - Plakophilin3 downregulation leads to a decrease in cell adhesion and promotes
      metastasis.
AB  - Plakophilin3 is a desmosomal plaque protein whose levels are reduced in poorly
      differentiated tumors of the oropharyngeal cavity and in invasive colon
      carcinomas. To test the hypothesis that plakophilin3 loss stimulates neoplastic
      progression, plakophilin3 expression was inhibited by DNA vector driven RNA
      interference in 3 epithelial cell lines, HCT116, HaCaT and fetal buccal mucosa.
      The plakophilin3-knockdown clones showed a decrease in cell-cell adhesion as
      assessed in a hanging drop assay, which was accompanied by an increase in cell
      migration. The HCT116 plakophilin3-knockdown clones showed a decrease in
      desmosome size as revealed by electron microscopy. These altered desmosomal
      properties were accompanied by colony formation in soft agar and growth to high
      density in culture. The HCT116-derived clones showed accelerated tumor formation
      in nude mice and increased metastasis to the lung, a phenotype consistent with
      the increased migration observed in vitro and is consistent with data from human
      tumors that suggests that plakophililn3 is lost in invasive and metastatic
      tumors. These data indicate that plakophilin3 loss leads to a decrease in cell
      cell adhesion leading to the stimulation of neoplastic progression and
      metastasis.

PMID- 18729190
TI  - Analysis of peripheral and local anti-tumor immune response in esophageal cancer
      patients after NY-ESO-1 protein vaccination.
AB  - NY-ESO-1 antigen is a prototype of a class of cancer/testis antigens. We carried
      out a clinical trial using NY-ESO-1 whole protein as a cancer vaccine for 13
      advanced cancer patients. We have recently reported that vaccine elicited humoral
      and cellular immune responses in 9 cancer patients including 4 esophageal cancer
      patients, and clinical responses were also observed in 4 of 5 evaluable patients.
      In this study, we analyzed the responses in 8 esophageal cancer patients
      including 4 newly enrolled patients. Patients were injected subcutaneously at
      biweekly intervals with NY-ESO-1 recombinant protein formulated with cholesterol
      bearing hydrophobized pullulan. Induction of antibody, and CD4 and CD8 T-cell
      responses were observed in 7, 7 and 6 patients, respectively, out of 8 patients.
      1 PR, 2 SD and 2 mixed clinical responses were observed in 6 evaluable patients.
      No significant adverse events were observed. Furthermore, we analyzed NY-ESO-1
      and MHC class I expression and the infiltration of immune cells into tumor
      samples obtained before and after vaccination from 4 patients by
      immunohistochemistry. The results showed 2 patients with disappearance of CD4 and
      CD8 T-cell infiltration, 1 patient with increase in the number of CD68(+)
      macrophages and 1 patient with tumor antigen loss in the progressive tumors
      following vaccinations. The induction of NY-ESO-1 immunity and some preferable
      clinical outcomes were observed in esophageal cancer patients by vaccination with
      NY-ESO-1. However, the tumors grew eventually by various mechanisms after
      vaccination.

PMID- 18729191
TI  - Diet diversity and the risk of squamous cell esophageal cancer.
AB  - A varied diet may have a favorable role against digestive tract cancers. We
      analyzed the relationship between diet diversity (i.e. measured by the number of
      different foods consumed at least once per week) and the risk of esophageal
      cancer. We considered data from a case-control study conducted between 1992 and
      1997 in northern Italy on 304 squamous cell esophageal cancer cases below age 78
      years and 743 controls admitted to hospital for acute, nonneoplastic conditions,
      unrelated to tobacco or alcohol consumption. There was a significant inverse
      association for total diet diversity: the multivariate odds ratio (OR), adjusted
      for age, sex, area of residence, education, tobacco smoking, alcohol drinking and
      non-alcohol energy intake was 0.42 (95% confidence interval, CI: 0.25-0.71) for
      subjects in the highest versus those in the lowest quartile of diversity. Inverse
      relations were also found for diversity within vegetables (OR = 0.34, 95% CI:
      0.21-0.55) and fruits (OR = 0.51, 95% CI: 0.33-0.80). No significant association
      was found for meat and cereal diversity. These results add epidemiological
      support to the dietary guidelines recommending a more varied diet, particularly
      in fruit and vegetables, for esophageal cancer prevention.

PMID- 18729192
TI  - PX-478, an inhibitor of hypoxia-inducible factor-1alpha, enhances
      radiosensitivity of prostate carcinoma cells.
AB  - Overexpression of hypoxia-inducible factor-1alpha (HIF-1alpha) in human tumors is
      associated with poor prognosis and poor outcome to radiation therapy. Inhibition
      of HIF-1alpha is considered as a promising approach in cancer therapy. The
      purpose of this study was to test the efficacy of a novel HIF-1alpha inhibitor PX
      478 as a radiosensitizer under normoxic and hypoxic conditions in vitro. PC3 and
      DU 145 prostate carcinoma cells were treated with PX-478 for 20 hr, and HIF
      1alpha protein level and clonogenic cell survival were determined under normoxia
      and hypoxia. Effects of PX-478 on cell cycle distribution and phosphorylation of
      H2AX histone were evaluated. PX-478 decreased HIF-1alpha protein in PC3 and DU
      145 cells. PX-478 produced cytotoxicity in both cell lines with enhanced toxicity
      under hypoxia for DU-145. PX-478 (20 mumol/L) enhanced the radiosensitivity of
      PC3 cells irradiated under normoxic and hypoxic condition with enhancement factor
      (EF) 1.4 and 1.56, respectively. The drug was less effective in inhibiting HIF
      1alpha and enhancing radiosensitivity of DU 145 cells compared to PC3 cells with
      EF 1.13 (normoxia) and 1.25 (hypoxia) at 50 mumol/L concentration. PX-478 induced
      S/G2M arrest in PC3 but not in DU 145 cells. Treatment of PC3 and DU 145 cells
      with the drug resulted in phosphorylation of H2AX histone and prolongation of
      gammaH2AX expression in the irradiated cells. PX-478 is now undergoing Phase I
      clinical trials as an oral agent. Although the precise mechanism of enhancement
      of radiosensitivity remains to be identified, this study suggests a potential
      role for PX-478 as a clinical radiation enhancer.

PMID- 18729193
TI  - CCAAT/enhancer binding protein-alpha polymorphisms occur more frequently than
      mutations in acute myeloid leukemia and exist across all cytogenetic risk groups
      and leukemia subtypes.
AB  - CCAAT/enhancer binding protein-alpha (CEBPA) belongs to a family of leucine
      zipper transcription factors necessary for late differentiation events of many
      cell types. CEBPA gene has recently been recognized as the target of genetic
      alterations in acute myeloid leukemia (AML). CEBPA mutations and polymorphisms
      were determined in a large series of Southeast Asian AML (n = 247) using
      polymerase chain reaction and direct sequencing. Chromosome and FLT3 mutation
      analyses were also undertaken. Thirty-two distinct types of nucleotide changes (7
      known and 25 novel mutations) were identified in 34 cases (13.8%). Three types of
      polymorphisms were found in 60 cases (24.3%) including a novel nt1401C>T
      polymorphism. All polymorphisms were located at the C-terminal region whereas the
      majority of mutations (62.5%) occurred at the N-terminal region. The most common
      polymorphism was the nt1175_1180dup resulting in the predicted P194_H195
      duplication protein in 50 cases. Although CEBPA mutations were predominantly
      associated with a normal karyotype (76%), 15.7% of patients with an unfavorable
      risk and 4.3% of patients with a favorable risk also had the mutations. Moreover,
      CEBPA polymorphisms were similarly found across all cytogenetic risk groups and
      occurred in all leukemia subtypes. FLT3 mutations were comparably discovered
      among patients with CEBPA mutations, polymorphisms and wild-type (26-30%). In
      conclusion, CEBPA polymorphisms occurred more frequently than CEBPA mutations and
      could be identified across all prognostic risk groups. The high occurrence of
      CEBPA polymorphisms should be recognized in order not to include this group of
      patients with CEBPA polymorphisms for prognostic evaluation of CEBPA mutations in
      any clinical trials.

PMID- 18729194
TI  - Hormone-related supplements and breast cancer risk: need for improved measurement
      of supplement use.

PMID- 18729195
TI  - Predictive value of thymidylate synthase expression in advanced colorectal cancer
      patients receiving fluoropyrimidine-based chemotherapy: evidence from 24 studies.
AB  - The published data about thymidylate synthase (TS) expression and its predictive
      value in advanced colorectal cancer (CRC) patients receiving fluoropyrimidine
      based chemotherapy seemed inconclusive. To derive a more precise estimation of
      the relationship, a metaanalysis was performed. Studies have been identified by
      searching PubMed and Embase. Inclusion criteria were advanced CRC patients,
      received fluoropyrimidine-based chemotherapy and evaluation of TS expression and
      overall response rate (ORR). The relative ratio (RR) for ORR in patients with low
      TS expression over those with high-TS expression with 95% confidence interval
      (CI) was calculated for each study as an estimation of the predictive effect of
      TS. A total of 24 studies including 1,112 patients were involved in this
      metaanalysis. The overall RR was 2.20 (95% CI, 1.82-2.66; p = 0.000). For studies
      evaluating TS expression in metastatic lesions, the pooled RR was 3.23 (95% CI,
      2.27-4.59; p = 0.000); for studies testing TS expression in primary lesions, a
      pooled RR of 1.89 (95% CI, 1.45-2.48; p = 0.000) was estimated. Focusing the
      analysis on immunohistochemistry (IHC)-based or RTPCR-based assessments, the
      pooled RR was 1.83 (95% CI, 1.44-2.34; p = 0.000) and 2.96 (95% CI, 2.07-4.22; p
      = 0.000), respectively. The results indicated that low-TS expression tumors in
      advanced CRC patients were more sensitive to fluoropyrimidine-based chemotherapy.
      Subgroup analyses indicated that the predictive value of TS expression evaluated
      in metastases was more prominent than that of primary lesions, and that TS
      expression tested by RTPCR was also of greater predictive value than by IHC.

PMID- 18729196
TI  - Acidosis induces multi-drug resistance in rat prostate cancer cells (AT1) in
      vitro and in vivo by increasing the activity of the p-glycoprotein via activation
      of p38.
AB  - Because solid growing tumors often show hypoxia and pronounced extracellular
      acidosis, the aim of this study was to analyze the impact of an acidotic
      environment on the activity of the p-glycoprotein (pGP) and on the cellular
      content and cytotoxicity of the chemotherapeutic drug daunorubicin in the AT1 R
      3327 Dunning prostate carcinoma cell line cultured in vitro and in vivo. In
      vitro, extracellular acidosis (pH 6.6) activated p38 and ERK1/2 and thereby
      induced daunorubicin resistance via a pronounced activation of pGP. De-novo
      protein synthesis was not necessary and analysis of transport kinetics indicated
      a fast and persistent pGP activation at pH 6.6 (when compared with 7.4).
      Intracellular acidification also induced daunorubicin resistance via activation
      of pGP, which was mediated by activation of p38 alone. In vivo, tumors were
      implanted subcutaneously, and the tumor pH was artificially lowered by forcing
      anaerobic metabolism. In vivo, the reduced extracellular pH of 6.6 was also able
      to induce daunorubicin resistance, which was abolished by inhibition of p38.
      These results suggest that pGP activity is dependent on extracellular pH in vitro
      and in vivo. Moreover, there is strong indication that this effect is mediated
      via activation of p38 in vivo. Activation of ERK is also suitable to induce pGP
      activity. Therefore, inhibition of p38 (and ERK) may be used to prevent acidosis
      induced increase in pGP activity and thereby attenuate multidrug resistance. In
      addition, supportive treatments reducing tumor acidosis may improve the cytotoxic
      effect of chemotherapeutic drugs.

PMID- 18729197
TI  - Intratumoral rhIL-12 administration in head and neck squamous cell carcinoma
      patients induces B cell activation.
AB  - The objectives of this study were to investigate the effects of intratumorally
      (i.t.) administered recombinant human interleukin-12 (rhIL-12) on the
      distribution and function of B cells in the primary tumors, the locoregional
      lymph nodes and peripheral blood of head and neck squamous cell carcinoma (HNSCC)
      patients. The initial characterization of the patients participating in the phase
      Ib and phase II studies has previously been reported. After rhIL-12 treatment,
      fewer secondary follicles with a broader outer region of the mantle zones and an
      increase in interfollicular B-blasts were seen in the enlarged lymph nodes
      compared with control HNSCC patients. The size of the germinal center (GC) was
      diminished, partly due to a decrease in the number of CD57+ GC cells that have
      been associated with immune suppression. These changes did not correlate with
      signs of apoptosis or CXCR5 expression by B cells. Strikingly, in 3 out of 4 IL
      12 treated patients, increased IFN-gamma mRNA expression by B cells was detected.
      In addition, a highly significant IgG subclass switch was seen in the plasma with
      more IgG1, less IgG2 and more IgG4, indicating a switch to T helper 1 phenotype.
      Finally, peritumoral B cell infiltration was a positive prognostic sign for
      overall survival in the 30 HNSCC patients investigated, irrespective of IL-12
      treatment. In conclusion, these data indicate that after i.t. IL-12 treatment in
      HNSCC, significant activation of the B cell and the B cell compartment occurred
      and that the presence of tumor infiltrating B cells correlated with overall
      survival of HNSCC patients.

PMID- 18729199
TI  - Gene silencing of beta-catenin in melanoma cells retards their growth but
      promotes the formation of pulmonary metastasis in mice.
AB  - Altered expression of beta-catenin, a key component of the Wnt signaling pathway,
      is involved in a variety of cancers because increased levels of beta-catenin
      protein are frequently associated with enhanced cellular proliferation. Although
      our previous study demonstrated that gene silencing of beta-catenin in melanoma
      B16-BL6 cells by plasmid DNA (pDNA) expressing short-hairpin RNA targeting the
      gene (pshbeta-catenin) markedly suppressed their growth in vivo, gene silencing
      of beta-catenin could promote tumor metastasis by the rearranging cell adhesion
      complex. In this study, we investigated how silencing of beta-catenin affects
      metastatic aspects of melanoma cells. Transfection of B16-BL6 cells with pshbeta
      catenin significantly reduced the amount of cadherin protein, a cell adhesion
      molecule binding to beta-catenin, with little change in its mRNA level. Cadherin
      derived fragments were detected in culture media of B16-BL6 cells transfected
      with pshbeta-catenin, suggesting that cadherin is shed from the cell surface when
      the expression of beta-catenin is reduced. The mobility of B16-BL6 cells
      transfected with pshbeta-catenin was greater than that of cells transfected with
      any of the control pDNAs. B16-BL6 cells stably transfected with pshbeta-catenin
      (B16/pshbeta-catenin) formed less or an equal number of tumor nodules in the lung
      than cells stably transfected with other plasmids when injected into mice via the
      tail vein. However, when subcutaneously inoculated, B16/pshbeta-catenin cells
      formed more nodules in the lung than the other stably transfected cells. These
      results raise concerns about the gene silencing of beta-catenin for inhibiting
      tumor growth, because it promotes tumor metastasis by reducing the amount of
      cadherin in tumor cells.

PMID- 18729198
TI  - Promoter hypermethylation of CDH13 is a common, early event in human esophageal
      adenocarcinogenesis and correlates with clinical risk factors.
AB  - Although the CDH13 gene has been shown to undergo epigenetic silencing by
      promoter methylation in many types of tumors, hypermethylation of this gene in
      Barrett's-associated esophageal adenocarcinogenesis has not been studied. Two
      hundred fifty-nine human esophageal tissues were therefore examined for CDH13
      promoter hypermethylation by real-time methylation-specific PCR. CDH13
      hypermethylation showed discriminative receiver-operator characteristic curve
      profiles, sharply demarcating esophageal adenocarcinoma (EAC) from esophageal
      squamous cell carcinoma (ESCC) and normal esophagus (NE) (p < 0.0001). CDH13
      normalized methylation values (NMV) were significantly higher in Barrett's
      esophagus (BE), dysplastic BE (D) and EAC than in NE (p < 0.0000001). CDH13
      hypermethylation frequency was 0% in NE but increased early during neoplastic
      progression, rising to 70% in BE, 77.5% in D and 76.1% in EAC. Both CDH13
      hypermethylation frequency and its mean NMV were significantly higher in BE with
      than without accompanying EAC. In contrast, only 5 (19.2%) of 26 ESCCs exhibited
      CDH13 hypermethylation. Furthermore, both CDH13 hypermethylation frequency and
      its mean NMV were significantly higher in EAC than in ESCC, as well as in BE or D
      vs. ESCC. Interestingly, mean CDH13 NMV was significantly lower in short-segment
      than in long-segment BE, a known clinical risk factor for neoplastic progression.
      Similarly, BE segment length was significantly lower in specimens with
      unmethylated than with methylated CDH13 promoters. 5-aza-2'-deoxycytidine
      treatment of OE33 EAC and KYSE220 ESCC cells reduced CDH13 methylation and
      increased CDH13 mRNA expression. These findings suggest that hypermethylation of
      CDH13 is a common, tissue-specific event in human EAC, occurs early during BE
      associated neoplastic progression, and correlates with known clinical neoplastic
      progression risk factors.

PMID- 18729200
TI  - Vitamin antioxidants, lipid peroxidation, tumour stage, the systemic inflammatory
      response and survival in patients with colorectal cancer.
AB  - Both the tumour growth and progression and the systemic inflammatory response
      have the potential to increase oxidative stress. We therefore examined the
      relationship between lipid-soluble antioxidant vitamins, lipid peroxidation, the
      systemic inflammatory response and survival in patients with primary operable (n
      = 53) and advanced inoperable (n = 53) colorectal cancer. Compared with those
      patients with primary operable colorectal cancer, patients with unresectable
      liver disease had significantly lower median concentrations of alpha-tocopherol
      (p < 0.001), lutein (p < 0.001), lycopene (p < 0.001), alpha-carotene (p < 0.01)
      and beta-carotene (p < 0.001) and higher malondialdehyde concentrations. An
      elevated systemic inflammatory response (Glasgow prognostic score, mGPS) was
      associated with a greater proportion of females (p < 0.05) and more advanced
      tumour stage (p < 0.05), lower circulating levels of retinol (p < 0.01), lutein
      (p < 0.01), lycopene (p < 0.01) and alpha- (p < 0.01) and beta-carotene but not
      MDA (p = 0.633). In the liver metastases group 41 patients died of their cancer
      and a further 1 patient died of intercurrent disease on follow-up. On univariate
      survival analysis, mGPS (p < 0.01), retinol (p < 0.001), alpha-tocopherol (p <
      0.05) and alpha-carotene (p < 0.05) were associated significantly with cancer
      specific survival. On multivariate survival analysis of these significant
      variables, only mGPS (p < 0.01) and retinol (p < 0.001) were independently
      associated with cancer-specific survival. The results of the present study showed
      that the systemic inflammatory response was associated with a reduction of lipid
      soluble antioxidant vitamins, whereas advanced tumour stage was associated with
      increased lipid peroxidation in patients with colorectal cancer. Of the
      antioxidant vitamins measured, only retinol was independently associated with
      cancer-specific survival.

PMID- 18729201
TI  - Characterization of four crystal polymorphs and a monohydrate of s-bupivacaine
      hydrochloride (levobupivacaine hydrochloride).
AB  - Five crystal forms of the amide-type local anesthetic S-bupivacaine hydrochloride
      (levobupivacaine) were prepared and characterized by means of thermal analytical
      methods, FTIR- and Raman-spectroscopy, powder X-ray diffractometry, and moisture
      sorption analysis. Commercial lots of the substance may consist of form A degrees
      , the thermodynamically stable form at 20 degrees C, and/or the metastable form
      C. Form A degrees shows a highly reversible transformation into form B (T(trs):
      85.3 degrees C) with a transition enthalpy of 4.6 kJ mol(-1). The hysteresis
      between the experimental transition temperatures is 3.5 K, indicating a very weak
      kinetic control. The hydrate shows a variable water content (0.71-1.14 mol/mol)
      between 10% and 90% relative humidity (RH) and dehydrates to form C under dry
      conditions or at elevated temperatures. All anhydrous forms transform to the
      hydrate at and above 90% RH (25 degrees C). Form C slowly converts to form A
      degrees on storage and is the polymorph with the highest hygroscopicity. At
      higher temperatures all forms transform into form D, which is kinetically stable
      at 20 degrees C. It is concluded that the forms A degrees , B, and D are
      enantiotropically related, whereas form C shows a monotropic relationship to
      these forms and is metastable in the entire temperature range.

PMID- 18729202
TI  - From natural bone grafts to tissue engineering therapeutics: Brainstorming on
      pharmaceutical formulative requirements and challenges.
AB  - Tissue engineering is an emerging multidisciplinary field of investigation
      focused on the regeneration of diseased or injured tissues through the delivery
      of appropriate molecular and mechanical signals. Therefore, bone tissue
      engineering covers all the attempts to reestablish a normal physiology or to
      speed up healing of bone in all musculoskeletal disorders and injuries that are
      lashing modern societies. This article attempts to give a pharmaceutical
      perspective on the production of engineered man-made bone grafts that are
      described as implantable tissue engineering therapeutics, and to highlight the
      importance of understanding bone composition and structure, as well as
      osteogenesis and bone healing processes, to improve the design and development of
      such implants. In addition, special emphasis is given to pharmaceutical aspects
      that are frequently minimized, but that, instead, may be useful for formulation
      developments and in vitro/in vivo correlations.

PMID- 18729203
TI  - Bicontinuous cyclosporin a loaded water-AOT/Tween 85-isopropylmyristate
      microemulsion: structural characterization and dermal pharmacokinetics in vivo.
AB  - Topical delivery of Cyclosporin A (CysA) is of great interest for the treatment
      of autoimmune skin disorders. Microemulsion systems prepared by
      AOT/Tween85/isopropyl myristate (IPM)/water possessing a potentially improved
      skin bioavailability of CysA were designed. The structure of microemulsions was
      investigated by diffusion-ordered NMR spectroscopy (DOSY) and differential
      scanning calorimetry (DSC) measurements. The DOSY measurements indicated the
      presence of bicontinuous and water-in-oil microemulsions depending on
      microemulsion composition. The DSC measurement confirmed that the microemulsion
      containing 30.0 wt% water was bicontinuous type, in agreement with the DOSY
      findings. We also evaluated the therapeutic advantage of dermal administration of
      CysA in rat model. Local (subcutaneous and skin), systemic concentrations and
      organ distribution (liver and kidney) were evaluated serially following topical
      and oral application of the drug. In rat dermal applied with the bicontinuous
      microemulsion containing CysA, the deposition of the drug into skin and
      subcutaneous fat was respectively almost 30 and 15-fold higher than the
      concentrations compared with oral administration. Systemic distribution in blood,
      liver and kidney was much lower following topical administration than that of
      following oral administration. With high local concentrations and minimal
      distribution to other organs via the circulation, topical microemulsion vehicle
      loaded with CysA might deliver maximal therapeutic effect to local tissue while
      avoiding side effects seen with systemic therapy. The histopathological findings
      revealed that the new bicontinuous microemulsion was a safe vehicle for topical
      drug delivery of CysA.

PMID- 18729204
TI  - Inhibition of cell adhesion by xARVCF indicates a regulatory function at the
      plasma membrane.
AB  - The cytoplasmic tail of cadherins is thought to regulate the strength and
      dynamics of cell-cell adhesion. Part of its regulatory activity has been
      attributed to a membrane-proximal region, the juxtamembrane domain (JMD), and its
      interaction with members of the p120 catenin subfamily. We show that titration of
      xARVCF, a member of this family, to the plasma membrane disrupts adhesion in the
      early embryo. Adhesion can be restored by coexpression of constitutively active
      Rac, suggesting that intracellular signaling is the primary cause in the loss of
      adhesion phenotype. Our observations suggest that the recruitment of p120 type
      catenins to the plasma membrane by the cadherin cytoplasmic tail may create
      protein complexes, which actively modulate the adhesion "status" of embryonic
      cells.

PMID- 18729205
TI  - Dynamic expression patterns of G protein-regulated inducer of neurite outgrowth 1
      (GRIN1) and its colocalization with Galphao implicate significant roles of
      Galphao-GRIN1 signaling in nervous system.
AB  - GRIN1 (Gprin 1) is a signaling molecule coexpression of which with constitutively
      active form of Galphao can stimulate neurite extensions in Neuro2a cells, yet its
      in vivo roles remain elusive. Here, we examine expression profiles of GRIN1
      during mouse development by in situ hybridization (ISH) and immunohistochemistry.
      ISH analysis revealed that GRIN1 expression was limited to the nervous system at
      all developmental stages tested: in the central nervous system, GRIN1 expression
      occurred within the entire embryonic mantle zones, while it became restricted to
      sets of nuclei at postnatal to adult stages. Immunohistochemistry using a GRIN1
      specific antibody demonstrated that GRIN1 colocalized with Galphao at neuronal
      dendrites and axons, but it was not detected in glial cells. These results
      suggest that Galphao-GRIN1 pathway could mediate significant roles in neuronal
      migration and differentiation at embryonic stages and exert functions in wiring
      and/or maintenance of specific neural circuitries at postnatal to adult stages.

PMID- 18729207
TI  - Syndactyly and preaxial synpolydactyly in the single Sfrp2 deleted mutant mice.
AB  - Secreted Frizzled-related protein 2 (Sfrp2) or Stromal Cell Derived Factor-5 (SDF
      5) is highly expressed in the developing limbs. Here we showed the single Sfrp2
      inactivation in mice resulted in syndactyly and preaxial synpolydactyly,
      predominantly in the hindlimbs. Tails were often kinked. A penetrance of the
      syndactyly was highest in 129/SvJ or CBA/N x 129/SvJ background and the phenotype
      was haploinsufficient. Preaxial synpolydactyly was seen in homozygous mutants in
      C57BL/6 x 129/SvJ. Of note, syndactyly showed retarded apoptosis of the second
      and the third interdigital spaces; concomitantly, mesodermal Msx2 expression was
      down-regulated. Impaired digital anlagen maturation was also noticeable in the
      same position. Preaxial synpolydactyly of the Sfrp2 mutants was a non-mirror
      image type and Shh independent. Although joint formation was not disrupted,
      chondrocyte maturation was preaxially disturbed. Our results suggest that the
      Sfrp2 deleted mice can be a useful animal model to study human
      syndactyly/preaxial synpolydactyly defects.

PMID- 18729206
TI  - G2R Cre reporter transgenic zebrafish.
AB  - The Cre/loxP site-specific recombination system has been widely used to
      manipulate DNA in vivo and to study gene function in the mouse by inducible
      transgenic and conditional gene targeting. To fully use this powerful genetic
      tool in a relatively new animal model, zebrafish, we generated reporter
      transgenic lines for easy detection of Cre recombinase activity in vivo. The
      transgenic fish lines, designated G2R, express two fluorescent protein genes, GFP
      and RFP, under the control of the ubiquitous promoter of the Xenopus EF1 alpha
      gene. The G2R animals change their color from green to red (G2R) after Cre
      mediated recombination and are useful for development of cell type specific Cre
      transgenic lines and for cell lineage and fate mapping studies in zebrafish.

PMID- 18729208
TI  - Expression pattern of Anosmin-1 during pre- and postnatal rat brain development.
AB  - Anosmin-1 participates in the development of the olfactory and GnRH systems.
      Defects in this protein are responsible for both the anosmia and the
      hypogonadotrophic hypogonadism found in Kallmann's syndrome patients.
      Sporadically, these patients also manifest some neurological symptoms that are
      not explained in terms of the developmental defects in the olfactory system. We
      describe the pattern of Anosmin-1 expression in the central nervous system during
      rat development using a novel antibody raised against Anosmin-1 (Anos1). The
      areas with Anos1-stained neurons and glial cells were classified into three
      groups: (1) areas with immunoreactivity from embryonic day 16 to postnatal day
      (P) 15; (2) areas with Anosmin-1 expression only at postnatal development; (3)
      nuclei with immunoreactivity only at P15. Our data show that Anos1
      immunoreactivity is detected in projecting neurons and interneurons within areas
      of the brain that may be affected in patients with Kallmann's syndrome that
      develop both the principal as well as sporadic symptoms.

PMID- 18729210
TI  - SSAO/VAP-1 protein expression during mouse embryonic development.
AB  - SSAO/VAP-1 is a multifunctional enzyme depending on in which tissue it is
      expressed. SSAO/VAP-1 is present in almost all adult mammalian tissues,
      especially in highly vascularised ones and in adipocytes. SSAO/VAP-1 is an amine
      oxidase able to metabolise various endogenous or exogenous primary amines. Its
      catalytic activity can lead to cellular oxidative stress, which has been
      implicated in several pathologies (atherosclerosis, diabetes, and Alzheimer's
      disease). The aim of this work is to achieve a study of SSAO/VAP-1 protein
      expression during mouse embryogenesis. Our results show that SSAO/VAP-1 appears
      early in the development of the vascular system, adipose tissue, and smooth
      muscle cells. Moreover, its expression is strong in several epithelia of the
      sensory organs, as well as in the development of cartilage sites. Altogether,
      this suggests that SSAO/VAP-1 enzyme could be involved in the differentiation
      processes that take place during embryonic development, concretely in tissue
      vascularisation.

PMID- 18729209
TI  - Corneal epithelial nuclear ferritin: developmental regulation of ferritin and its
      nuclear transporter ferritoid.
AB  - The corneal epithelium is exposed to reactive oxygen species that are potentially
      deleterious to nuclear DNA. However, our previous studies show that corneal
      epithelial cells have a novel, developmentally regulated mechanism for protection
      from such damage that involves having the iron-sequestering molecule, ferritin,
      in the nucleus. Nuclear localization of ferritin is achieved through the action
      of a tissue-specific nuclear transporter, ferritoid, which is itself a ferritin
      family member. Here, we show that during development ferritoid appears before
      ferritin. At this time, ferritoid is cytoplasmic, suggesting that its nuclear
      transport function requires an interaction with ferritin. To examine the
      developmental regulation of these two interacting components, cultured corneas
      were treated with the iron chelator deferoxamine. The results show that, while
      iron-mediated translational regulation is involved in the synthesis of both
      molecules, ferritoid is also transcriptionally regulated, demonstrating that
      these family members--whose functions depend upon one another--are regulated
      differently.

PMID- 18729211
TI  - Kv11.1 channel subunit composition includes MinK and varies developmentally in
      mouse cardiac muscle.
AB  - The Kv11.1 (also ERG1) K(+) channel underlies cardiac I(Kr), a current that
      contributes to repolarization in mammalian heart. In mice, I(Kr) current density
      decreases with development and studies suggest that changes in the structure
      and/or properties of the heteromultimeric I(Kr)/Kv11.1 channel are responsible.
      Here, using immunohistochemistry, we report that total Kv11.1 alpha subunit
      protein is more abundant in neonatal heart and is distributed throughout both
      adult and neonatal ventricles with greater abundance in epicardia. Immunoblots
      reveal that the alpha subunit alternative splice variant, Kv11.1a, is more
      abundant in adult heart while the Kv11.1b variant is more abundant in neonatal
      heart. Additionally, MinK channel subunit protein is shown to co-assemble with
      Kv11.1 protein and is more abundant in neonatal heart. In summary, Kv11.1/I(Kr)
      channel composition varies developmentally and the higher I(Kr) current density
      in neonatal heart is likely attributable to higher abundance of Kv11.1/I(Kr)
      channels, more specifically, the Kv11.1b splice variant.

PMID- 18729212
TI  - Germline transgenesis of zebrafish using the medaka Tol1 transposon system.
AB  - Tol1 is a DNA-based transposable element first identified from an albino mutant
      medaka fish. It has been demonstrated to function as an efficient gene transfer
      vector in mammalian cells. We now demonstrate Tol1 germline transgenesis in
      zebrafish. A construct containing the green fluorescence protein (GFP) reporter
      gene inserted between the Tol1 arms was microinjected together with Tol1
      transposase mRNA into fertilized eggs. Sustained GFP expression was observed in
      88% of 1-month-old fish, suggesting efficient transposon integration into somatic
      cells. Eleven of 24 adult GFP-positive fish yielded GFP-positive progeny.
      Sequencing analysis of Tol1 insertion sites in GFP-positive progeny confirmed
      Tol1 transposition-mediated integrations into zebrafish chromosomes. We also
      observed functional independence of the Tol1 transposase-substrate system from
      that of Tol2, another medaka-derived transposon. Coupled with its previously
      demonstrated maximal cargo capacity of >20 kb, Tol1 could serve as a useful
      addition to the zebrafish genetic engineering toolbox.

PMID- 18729213
TI  - Multiple regulatory elements mediating neuronal-specific expression of zebrafish
      sodium channel gene, scn8aa.
AB  - Zebrafish scn8aa sodium channels mediate the majority of sodium conductance,
      which is essential for the embryonic locomotor activities. Here, we investigated
      the transcriptional regulation of scn8aa in developing zebrafish embryos by
      constructing a GFP reporter driven by a 15-kb fragment of scn8aa gene designed as
      scn8aa:GFP. GFP expression patterns of scn8aa:GFP temporally and spatially
      recapitulated the expression of endogenous scn8aa mRNA during zebrafish embryonic
      development, with one exception in the inner nuclear layer of the retina. Three
      novel elements, along with an evolutionarily conserved element shared with mouse
      SCN8A, modulated neuronal-specific expression of scn8aa. The deletion of each
      positive element reduced the expression levels in neurons without inducing
      ectopic GFP expression in non-neuronal cells. Our results demonstrate that these
      four regulatory elements function cooperatively to enhance scn8aa expression in
      the zebrafish nervous system.

PMID- 18729214
TI  - Determination of microRNAs in mouse preimplantation embryos by microarray.
AB  - Expression profile of microRNA (miRNA) in mouse oocytes and preimplantation
      embryos has been revealed by a novel high throughput microarray assay. A total of
      97 (43 "new" and 54 known) including mouse, human, and predicted miRNAs have been
      discovered in the preimplantation mouse embryos which can be classified into
      developmental stage-dependent groups and non-stage-dependent group according to
      the statistical analysis of the expression patterns. Potential gene targets of
      each group of miRNAs are estimated by TargetsScan system and significantly
      changed signaling pathways and biological processes underlying these gene targets
      are searched by PANTHER classification system between the stage-dependent miRNAs
      and the non-stage-dependent miRNAs. Expression of some miRNAs is confirmed by
      reverse transcriptase-polymerase chain reaction. It is shown that dynamic
      synthesis and degradation of miRNAs coexists in the preimplantation development
      of mouse embryos. However, the overall quantity of miRNAs and percentage of the
      stage-dependent miRNAs increase as the preimplantation embryos develop.

PMID- 18729216
TI  - Relating cell and tissue mechanics: implications and applications.
AB  - The Differential Adhesion Hypothesis (DAH) posits that differences in adhesion
      provide the driving force for morphogenetic processes. A manifestation of
      differential adhesion is tissue liquidity and a measure for it is tissue surface
      tension. In terms of this property, DAH correctly predicts global developmental
      tissue patterns. However, it provides little information on how these patterns
      arise from the movement and shape changes of cells. We provide strong qualitative
      and quantitative support for tissue liquidity both in true developmental context
      and in vitro assays. We follow the movement and characteristic shape changes of
      individual cells in the course of specific tissue rearrangements leading to
      liquid-like configurations. Finally, we relate the measurable tissue-liquid
      properties to molecular entities, whose direct determination under realistic
      three-dimensional culture conditions is not possible. Our findings confirm the
      usefulness of tissue liquidity and provide the scientific underpinning for a
      novel tissue engineering technology.

PMID- 18729215
TI  - Fungiform papilla pattern: EGF regulates inter-papilla lingual epithelium and
      decreases papilla number by means of PI3K/Akt, MEK/ERK, and p38 MAPK signaling.
AB  - Fungiform papillae are epithelial taste organs that form on the tongue, requiring
      differentiation of papillae and inter-papilla epithelium. We tested roles of
      epidermal growth factor (EGF) and the receptor EGFR in papilla development.
      Developmentally, EGF was localized within and between papillae whereas EGFR was
      progressively restricted to inter-papilla epithelium. In tongue cultures, EGF
      decreased papillae and increased cell proliferation in inter-papilla epithelium
      in a concentration-dependent manner, whereas EGFR inhibitor increased and fused
      papillae. EGF preincubation could over-ride disruption of Shh signaling that
      ordinarily would effect a doubling of fungiform papillae. With EGF-induced
      activation of EGFR, we demonstrated phosphorylation in PI3K/Akt, MEK/ERK, and p38
      MAPK pathways; with pathway inhibitors (LY294002, U0126, SB203580) the EGF
      mediated decrease in papillae was reversed, and synergistic actions were shown.
      Thus, EGF/EGFR signaling by means of PI3K/Akt, MEK/ERK, and p38 MAPK contributes
      to epithelial cell proliferation between papillae; this biases against papilla
      differentiation and reduces numbers of papillae.

PMID- 18729217
TI  - The Caenorhabditis elegans DDX-23, a homolog of yeast splicing factor PRP28, is
      required for the sperm-oocyte switch and differentiation of various cell types.
AB  - DEAD/H-box proteins are involved in various aspects of RNA metabolism. Here we
      report the developmental function of a DEAD-box protein, DDX-23, in
      Caenorhabditis elegans, which has significant homology with the yeast splicing
      factor PRP28. We found by RNAi and mutant analyses that DDX-23 is essential for
      both embryonic and post-embryonic development, and required for differentiation
      of the majority of somatic tissues. When the germline function of ddx-23 was
      inhibited, hermaphrodite animals showed a reduced number of germ cells and failed
      to switch from spermatogenesis to oogenesis. These phenotypes were similar to
      those of the mutants of the three DEAH-box proteins (MOG-1, MOG-4, and MOG-5)
      whose yeast orthologs are involved in the pre-mRNA splicing pathway. We speculate
      that DDX-23 functions with the three MOG proteins in the same pathway to regulate
      tissue differentiation, robust germline proliferation, and the sperm/oocyte
      switch through modulations of ribonucleoprotein complexes.

PMID- 18729218
TI  - Iris as a recipient tissue for pigment cells: organized in vivo differentiation
      of melanocytes and pigmented epithelium derived from embryonic stem cells in
      vitro.
AB  - Regenerative transplantation of embryonic stem (ES) cell-derived melanocytes into
      adult tissues, especially skin that includes hair follicles or the hair follicle
      itself, generally not possible, whereas that of ES cell-derived pigmented
      epithelium was reported previously. We investigated the in vivo differentiation
      of these two pigment cell types derived from ES cells after their transfer into
      the iris. Melanocytes derived from ES cells efficiently integrated into the iris
      and expanded to fill the stromal layer of the iris, like those prepared from
      neonatal skin. Transplanted pigmented epithelium from either ES cells or the
      neonatal eye was also found to be integrated into the iris. Both types of these
      regenerated pigment cells showed the correct morphology. Regenerated pigment
      epithelium expressed its functional marker. Functional blocking of signals
      required for melanocyte development abolished the differentiation of transplanted
      melanocytes. These results indicate successful in vivo regenerative transfer of
      pigment cells induced from ES cells in vitro.

PMID- 18729219
TI  - Rescue of renal hypoplasia and cystic dysplasia in Bcl-2 -/- mice expressing Bcl
      2 in ureteric bud derived epithelia.
AB  - Bcl-2 is the founding member of a family of proteins that influence apoptosis.
      Loss of bcl-2 results in renal hypoplasia/cystic dysplasia at birth. Here, we
      examined whether re-expression of bcl-2 throughout the ureteric bud and its
      derived epithelia would restore a normal renal phenotype in bcl-2 -/- mice. Re
      expression of bcl-2 in the ureteric bud/collecting duct of bcl-2 -/- mice
      increased nephron numbers, diminished glomerular hypertrophy, and increased
      nephrogenic zone size. Unlike bcl-2 -/- mice which have gross renal cyst
      formation, few renal cysts were present in mice re-expressing bcl-2. We have
      previously shown increased apoptosis and proliferation, as well as aberrant
      protein tyrosine phosphatase 1B expression, accompanied cystic changes in bcl-2 
      /- mice. These changes were not observed when bcl-2 was re-expressed in the
      ureteric bud/collecting duct system. Thus, expression of bcl-2 in the ureteric
      bud/collecting duct resulted in increased nephron numbers partially rescuing
      renal hypoplasia/cystic dysplasia in bcl-2 -/- mice.

PMID- 18729220
TI  - Muscle development is disrupted in zebrafish embryos deficient for fibronectin.
AB  - After somitogenesis, skeletal muscle precursors elongate into muscle fibers that
      anchor to the somite boundary, which becomes the myotome boundary. Fibronectin
      (Fn) is a major component of the extracellular matrix in both boundaries.
      Although Fn is required for somitogenesis, effects of Fn disruption on subsequent
      muscle development are unknown. We show that fn knockdown disrupts myogenesis.
      Muscle morphogenesis is more disrupted in fn morphants than in a mutant where
      initial somite boundaries did not form, aei/deltaD. We quantified this disruption
      using the two-dimensional Wavelet-Transform Modulus Maxima method, which uses the
      variation of intensity in an image with respect to the direction considered to
      characterize the structure in a cell lattice. We show that fibers in fn morphants
      are less organized than in aei/deltaD mutant embryos. Fast- and slow-twitch
      muscle lengths are also more frequently uncoupled. These data suggest that fn may
      function to regulate fiber organization and limit fast-twitch muscle fiber
      length.

PMID- 18729221
TI  - Enhancer detection and developmental expression of zebrafish sprouty1, a member
      of the fgf8 synexpression group.
AB  - Signaling pathways mediated by receptor tyrosine kinases (RTKs) are under
      positive and negative regulation, and misregulation of RTK signaling results in
      developmental defects and malignancy. A major class of antagonists of Fgf and Egf
      signaling are the Sprouty proteins. Through an enhancer detection approach, we
      isolated the sprouty1 (spry1) gene, expressed in multiple developing organs
      during embryogenesis. We analyzed expression of spry1 between tail bud stage and
      10 days postfertilization. From the tail bud stage on, transcript and reporter
      are detected in the craniofacial region and in the mid-hindbrain boundary, where
      expression persists until adulthood. Further expression domains are the
      telencephalon, hindbrain, dorsal diencephalon and epiphysis, branchial arches,
      pituitary, and the tubular gill epithelium. In the trunk spry1 is also
      prominently expressed in pronephros, the lateral line and tail fin. Sprouty1 acts
      in Fgf signaling downstream of Fgfr1, as its expression is abrogated through the
      small molecule inhibitor of this receptor, SU5402.

PMID- 18729222
TI  - A peek inside the neurosecretory brain through Orthopedia lenses.
AB  - The wealth of expression and functional data presented in this overview discloses
      the homeogene Orthopedia (Otp) as critical for the development of the
      hypothalamic neuroendocrine system of vertebrates. Specifically, the results
      depict the up-to-date portrait of the regulation and functions of Otp. The
      development of neuroendocrine nuclei relies on Otp from fish to mammals, as
      demonstrated for several peptide and hormone releasing neurons. Additionally, the
      activity of Otp is essential for the induction of the dopaminergic phenotype in
      the hypothalamus of vertebrates. Recent insights into the pathways required for
      Otp regulation have revealed the implication of the main extracellular signals
      acting during hypothalamic development. Alterations in these pathways are
      involved in several neuronal disorders, and the resultant downstream
      misregulation of Otp might impair the development of the hypothalamus, and be
      therefore responsible for the neuroendocrine dysfunctions that typify these
      diseases.

PMID- 18729223
TI  - Monocilia in the embryonic mouse heart suggest a direct role for cilia in cardiac
      morphogenesis.
AB  - Primary cilia are required for signaling, chemosensing and mechanosensing in many
      fluid-filled organs, thus cilia could also have a direct role in heart
      development. They are essential to the development of cardiac left-right (LR)
      asymmetry by means of their function at the embryonic organizer (node). We show
      that cilia are found in the mouse embryo heart at embryonic day (e) 9.5-e12.5. We
      demonstrate abnormal development of the endocardial cushions (ECCs) and compact
      myocardium (CM) in e9.5 mouse embryos with absent cilia. In contrast, hearts from
      embryos with abnormal LR development due to paralyzed, but structurally normal,
      node cilia show less severe ECC defects and normal CM. These observations suggest
      that a subset of cilia called cardiac cilia are required in cardiac development
      independently from their function in LR development. One possible function of
      cardiac cilia is as mechanosensors, integrating flow, cardiac function, and
      morphogenesis.

PMID- 18729225
TI  - The Ars insulator facilitates I-SceI meganuclease-mediated transgenesis in the
      sea urchin embryo.
AB  - For the efficient generation of transgenic sea urchins, we have adopted an I-SceI
      meganuclease-mediated transgenesis method. Several types of promoter-GFP gene
      constructs flanked by two I-SceI recognition sequences were co-injected with I
      SceI into sea urchin fertilized eggs. Using cell-lineage-specific promoter
      constructs, the frequency of transgene expression was elevated, and their level
      of mozaicism was reduced. The addition of the Ars insulator sequence, which is
      known to block the enhancer activity and protect transgenes from position
      effects, led to a reduction in ectopic transgene expression and an elevation of
      transgene expression frequency in this I-SceI-mediated system. However, the
      magnitude of the effects of the Ars insulator was dependent upon the promoter
      constructs. QPCR analysis also showed that the Ars insulator increases the
      transgene copy number. These results suggest that the I-SceI-mediated method
      using the Ars insulator is advantageous for transgenesis in the sea urchin
      embryo.

PMID- 18729224
TI  - Cortical development in the presenilin-1 null mutant mouse fails after splitting
      of the preplate and is not due to a failure of reelin-dependent signaling.
AB  - Cortical development is disrupted in presenilin-1 null mutant (Psen1-/-) mice.
      Prior studies have commented on similarities between Psen1-/- and reeler mice.
      Reelin induces phosphorylation of Dab1 and activates the phosphatidylinositol 3
      kinase (PI3K)/Akt pathway. Psen1 is known to modulate PI3K/Akt signaling and both
      known reelin receptors (apoER2 and VLDLR) are substrates for Psen1 associated
      gamma-secretase activity. The purpose of this study was to determine whether
      reelin signaling is disrupted in Psen1-/- mice. We show that, while Dab1 is
      hypophosphorylated late in cortical development in Psen1-/- mice, it is normally
      phosphorylated at earlier ages and reelin signaling is intact in Psen1-/- primary
      neuronal cultures. gamma-secretase activity was also not required for reelin
      induced phosphorylation of Dab1. Unlike reeler mice the preplate splits in Psen1
      /- brain. Thus cortical development in Psen1-/- mice fails only after splitting
      of the preplate and is not due to an intrinsic failure of reelin signaling.

PMID- 18729226
TI  - A critical evaluation of specific aspects of joint development.
AB  - Synovial joint formation has been divided into two phases; the formation of the
      anlagen of the opposing bones and the interzone and the later formation of the
      joint cavity. Here we review current theories on the mechanism by which these
      events are achieved in the joints of the developing limb.

PMID- 18729228
TI  - Renal glomerulogenesis in medaka fish, Oryzias latipes.
AB  - We provide an overview of glomerulogenesis in medaka from the embryo to the adult
      by means of in situ hybridization with the wt1 gene as a marker as well as
      histology and three-dimensional images. The pronephric glomus starts to develop
      in the intermediate mesoderm during early somitogenesis, is completed before
      hatching, and persists throughout the lifetime of the fish. Within 5 days after
      hatching, mesonephric glomerulus formation begins in the caudomedial end of the
      pronephric sinus and duct area. The number of glomeruli reaches approximately 200
      300 in each kidney within 2 months after hatching. wt1 expression during nephron
      maturation served as a marker for the formation of the mesenchymal condensate and
      the nephrogenic body. Existence of mesenchymal condensates and persistence of wt1
      expression in the adult kidney suggest that the mesonephros retains precursor
      cells that may be capable of contributing to neoglomerulogenesis during
      adulthood.

PMID- 18729229
TI  - Expression of protocadherin-1 (Pcdh1) during mouse development.
AB  - Protocadherin-1 (Pcdh1) is a member of the delta-protocadherin subgroup of non
      clustered protocadherins. We studied the expression of Pcdh1 from the early
      embryonic to the adult stage of mouse development by semi-quantitative RT-PCR and
      in situ hybridization. Pcdh1 can be detected as early as embryonic day 9.5. In
      early embryogenesis, expression is especially prominent in blood vessels. During
      later development and in the adult mouse, organs derived from the embryonic gut,
      such as the esophagus, intestines, liver, lung, and submandibular gland, contain
      epithelia and other types of tissues that are Pcdh1-positive. Other positive
      organs include the brain, spinal cord, retina, peripheral ganglia, the inner ear,
      hair follicles, kidney, vagina, uterus, placenta, testis, prostate, and the
      seminal gland. The tight spatial and temporal regulation of Pcdh1 expression
      suggests that this protocadherin plays multiple roles not only during development
      but also in mature tissues and organs in the mouse.

PMID- 18729231
TI  - Expression of TMEM16 paralogs during murine embryogenesis.
AB  - The TMEM16 protein family has recently been identified through several different
      experimental strategies including bioinformatic and microarray-based approaches.
      In mice and humans, there exist 10 paralogs with each containing eight putative
      transmembrane domains and a conserved C-terminal domain of unknown function.
      Mutation of at least one member of this family is associated with a human
      disorder, and several members of this gene family are overexpressed in different
      types of cancer. Despite their apparent relevance to normal development and
      disease, little is known about the expression of TMEM16 paralogs during embryonic
      development. Here, we provide a phylogenetic analysis of mouse and human TMEM16
      paralogs and report the expression of Tmem16a, Tmem16b, Tmem16c, Tmem16f,
      Tmem16h, Tmem16j, and Tmem16k during murine embryogenesis with an emphasis on the
      respiratory, digestive, skeletal, and integumentary systems. These data should
      encourage investigations into the functions of TMEM16 paralogs in vertebrate
      development.

PMID- 18729230
TI  - Zebrafish mutants with disrupted early T-cell and thymus development identified
      in early pressure screen.
AB  - Generation of mature T lymphocytes requires an intact hematopoietic stem cell
      compartment and functional thymic epithelium. We used the zebrafish (Danio rerio)
      to isolate mutations that affect the earliest steps in T lymphopoiesis and thymic
      organogenesis. Here we describe the results of a genetic screen in which
      gynogenetic diploid offspring from heterozygous females were analyzed by whole
      mount in situ hybridization for the expression of rag-1. To assess immediately if
      a global defect in hematopoiesis resulted in the mutant phenotype, alpha
      embryonic globin expression was simultaneously assayed for multilineage defects.
      In this report, we present the results obtained with this strategy and show
      representative mutant phenotypes affecting early steps in T-cell development
      and/or thymic epithelial cell development. We discuss the advantage of this
      strategy and the general usefulness of the zebrafish as a model system for
      vertebrate lymphopoiesis and thymic organogenesis.

PMID- 18729234
TI  - Myotonic dystrophy protein kinase is expressed in embryonic myocytes and is
      required for myotube formation.
AB  - Myotonic dystrophy (DM1) is a multi-systemic disease caused by a triplet
      nucleotide repeat expansion in the 3' untranslated region of the gene coding for
      myotonic dystrophy protein kinase (DMPK). The primary pathophysiology of DM1 is
      thought to result from RNA transport and processing defects. The function of DMPK
      in development or any potential role in DM1 remains unknown. Here we report a
      novel role for DMPK in myogenesis. We have discovered a specific expression
      pattern of DMPK in mouse and chick embryonic development. DMPK is expressed in
      postmitotic cardiac and skeletal myocytes and developmental signaling centers.
      During cardiac myocyte maturation, DMPK migrates from perinuclear to cellular
      membrane localization. Manipulating DMPK levels in cultured cardiac and skeletal
      myocytes has revealed a key role for DMPK in myocyte differentiation.
      Overexpression of DMPK induces cell rounding and apoptosis in myocytes. In
      addition, DMPK is necessary for myogenin expression in differentiating C2C12
      myoblasts.

PMID- 18729235
TI  - Oncogenesis by retroviruses: old and new paradigms.
AB  - Retroviruses are associated with a variety of diseases including an array of
      malignancies, immunodeficiencies and neurological disorders. In particular,
      studies of oncogenic retroviruses established fundamental principles of modern
      molecular cancer biology. Studies of avian Rous sarcoma virus (RSV) led to the
      discovery of the viral oncogene src, and this was followed by the discovery of
      other viral oncogenes in retroviruses of mammals including rodents, cats, monkeys
      and so forth. Studies of the viral oncogenes in turn led to the discovery of
      cellular proto-oncogenes in the host genome; cellular oncogenes have been shown
      to be activated in a variety of human cancers, including those with no viral
      involvement. Oncogenic animal retroviruses can be divided into two groups based
      on their mechanisms of tumourigenesis, acute transforming retroviruses and
      nonacute retroviruses. Acute transforming retroviruses are typically replication
      defective and they induce tumours rapidly due to expression of their viral
      oncogenes. Nonacute retroviruses are replication competent and they induce
      tumours with longer latencies, by activating cellular proto-oncogenes in the
      tumour cells; this results from insertion of proviral DNA in the vicinity of the
      activated proto-oncogene. More recently, human T-cell leukaemia virus type I
      (HTLV-I) was discovered as an etiological agent of human cancer (adult T-cell
      leukaemia [ATL]); this virus also encodes regulatory genes some of which are
      important for its oncogenic potential. Most recently, the retroviral structural
      protein Envelope (Env) has been shown to be directly involved in oncogenic
      transformation for certain retroviruses. Env-induced transformation is a new
      paradigm for retroviral oncogenesis. In this review, we will summarise research
      on retrovirus oncogenic transformation over the past 100 years since the first
      published report of an oncogenic virus with particular attention to Env-induced
      transformation.

PMID- 18729236
TI  - A direct and rapid leaf water extraction method for isotopic analysis.
AB  - Isotopic measurements of leaf water have provided insights into a range of
      ecophysiological and biogeochemical processes, but require an extraction step
      which often constitutes the major analytical bottleneck in large-scale studies.
      Current standard procedures for leaf water analysis are based on cryogenic vacuum
      or azeotrophic distillation, and are laborious, require sophisticated
      distillation lines and the use of toxic materials. We report a rapid technique
      based on centrifugation/filtration of leaf samples pulverised in their original
      sampling tubes, using a specifically adapted, simple apparatus. The leaf water
      extracts produced are suitable for isotopic analysis via pyrolysis gas
      chromatography isotope ratio mass spectrometry (PYR/GC/IRMS). The new method was
      validated against cryogenic vacuum distillation and showed an overall accuracy of
      +/-0.5 per thousand (nine grouped comparisons, n = 110) over a range of 21 per
      thousand. Effects due to the presence of soluble carbohydrates were near the
      detection limits for most samples analysed, and these effects could be corrected
      for (the extracted soluble organics could also be used for isotopic analysis).
      The extraction time for a routine eight-sample subset was reduced from 4 h
      (cryogenic distillation) to 45 min, limited only by the size of the centrifuge(s)
      used. This method provides a rapid, low-cost and reliable alternative to
      conventional vacuum and other distillation methods that can alleviate current
      restrictions on ecosystem- and global-scale studies that require high-throughput
      leaf water isotopic analysis.

PMID- 18729237
TI  - Prognostic MRI biomarkers of treatment efficacy for retinopathy.
AB  - There is a pressing need for retina-specific imaging biomarkers that robustly
      measure early (subclinical) changes in physiology, are linked to the
      histopathology responsible for vision loss, and, importantly, predict treatment
      efficacy. This review focuses on the following four MRI markers that we have
      developed and applied in preclinical and clinical settings: preretinal vitreous
      oxygen level (a steady-state biomarker of inner retinal oxygen tension); leakage
      of contrast agent into the vitreous (a steady-state biomarker of blood-retinal
      barrier permeability surface area product); change in preretinal vitreous oxygen
      tension during a hyperoxic provocation (a functional biomarker of vascular
      autoregulation); and retinal uptake of systemically administered manganese during
      a visual task (a functional biomarker of intraretinal ion regulation). We
      conclude that functional biomarkers are most promising for prognostic evaluation
      of treatment efficacy earlier in the course of retinopathy than is currently
      possible.

PMID- 18729238
TI  - S4(13)-PV cell penetrating peptide and cationic liposomes act synergistically to
      mediate intracellular delivery of plasmid DNA.
AB  - BACKGROUND: Cell penetrating peptides have been successfully used to mediate the
      intracellular delivery of a wide variety of molecules of pharmacological
      interest. The main aim of the present work was to evaluate the potential of the
      S4(13)-PV cell penetrating peptide to mediate the intracellular delivery of
      plasmid DNA, aiming at its use in gene therapy applications. The S4(13)-PV cell
      penetrating peptide is a chimeric peptide that results from the combination of a
      cell penetrating sequence derived from the Dermaseptin S4 peptide with the
      nuclear localization signal present in the Simian Virus 40 (SV40) large T
      antigen. METHODS: S4(13)-PV cell penetrating peptide and cationic liposomes
      composed of 1,2-dioleoyl-3-trimethylammonium-propane:1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine were complexed with pDNA at different charge ratios.
      Complexation of pDNA was assessed by gel electrophoresis. Luciferase assay,
      fluorescence microscopy and fluorescence-activated cell sorting analysis were
      used to evaluate reporter gene delivery to TSA and HeLa cells. Cytotoxicity of
      the pDNA complexes was assessed by Alamar blue assay. RESULTS: Complexes obtained
      through electrostatic association of the S4(13)-PV cell penetrating peptide with
      plasmid DNA are able to very efficiently mediate transfection, particularly at
      high peptide/DNA charge ratios. Additionally, our results clearly demonstrate
      that, both in HeLa and TSA cells, ternary complexes, resulting from association
      of cationic liposomes to peptide/DNA complexes, are significantly more efficient
      in mediating transfection than the corresponding peptide/DNA or cationic
      liposome/DNA complexes. CONCLUSIONS: Overall, our data highlight the potential of
      cell penetrating peptides for the development of improved nonviral gene delivery
      systems.

PMID- 18729239
TI  - Gas-phase proton-transfer pathways in protonated histidylglycine.
AB  - Pathways for proton transfer in the histidylglycine cation are examined in the
      gas-phase environment with the goal of understanding the mechanism by which
      protons may become mobile in proteins with basic amino acid residues. An
      extensive search of the potential energy surface is performed using density
      functional theory (DFT) methods. After corrections for zero-point energy are
      included, it is found that all the lowest energy barriers for proton transfer
      between the N-terminus and the imidazole ring have heights of only a few
      kcal/mol, while those between the imidazole ring and the backbone amide oxygen
      have heights of approximately 15 kcal/mol when the proton is moving from the ring
      to the backbone and only a few kcal/mol when moving from the backbone to the
      imidazole ring. In mass spectrometric techniques employing collision-induced
      dissociation to dissociate protein complex ions or to fragment peptides, these
      barriers can be overcome, and the protons mobilized.

PMID- 18729240
TI  - Sustained baculovirus-mediated expression in myogenic cells.
AB  - BACKGROUND: Baculovirus has emerged as a promising gene delivery vector due to
      its low cytotoxicity and nonreplication nature in mammalian cells. However,
      baculovirus-mediated expression is transient and generally lasts less than 14
      days, which could restrict its application in the treatment of diseases requiring
      stable transgene expression. METHODS: We transduced myoblast cell lines C2C12,
      Sol 8 and primary myoblasts with a baculovirus expressing the enhanced green
      fluorescent protein (EGFP) under the control of cytomegalovirus immediate-early
      promoter and measured the transduction efficiency by flow cytometry. Myogenic
      differentiation was induced after transduction and the longevity of EGFP
      expression was monitored by fluorescence microscopy. The myogenic differentiation
      was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). The
      persistence of the egfp DNA and transcripts was monitored by real-time PCR and
      quantitative real-time RT-PCR. RESULTS: Baculovirus efficiently transduced C2C12,
      Sol 8 and the primary myoblasts. The transgene expression persisted for a
      prolonged period of time (at least 63 days) in the cells differentiating into
      myotubes, but was transient in HeLa cells (<7 days). The sustained expression
      paralleled the myogenic differentiation and stemmed from the intracellular
      persistence of egfp DNA and mRNA. CONCLUSIONS: The transgene delivered by
      baculovirus persists in the myotubes and endows sustained expression, which is
      distinct from its rapid degradation and transient expression in other cell types.
      These findings justify the future use of baculovirus for muscle-based gene
      therapy.

PMID- 18729241
TI  - Antibodies against RNA hydrolyze RNA and DNA.
AB  - Immunization of animals with DNA leads to the production of anti-DNA antibodies
      (Abs) demonstrating both DNase and RNase activities. It is currently not known
      whether anti-RNA Abs can possess nuclease activities. In an attempt to address
      this question, we have shown that immunization of three rabbits with complex of
      RNA with methylated BSA (mBSA) stimulates production of IgGs with RNase and DNase
      activities belonging to IgGs, while polyclonal Abs from three non-immunized
      rabbits and three animals immunized with mBSA are catalytically inactive.
      Affinity chromatography of IgGs from the sera of autoimmune (AI) patients on DNA
      cellulose usually demonstrates a number of fractions, all of which effectively
      hydrolyze both DNA and RNA, while rabbit catalytic IgGs were separated into Ab
      subfractions, some of which demonstrated only DNase activity, while others
      hydrolyzed RNA faster than DNA. The enzymic properties of the RNase and DNase
      IgGs from rabbits immunized with RNA distinguish them from all known canonical
      RNases and DNases and DNA- and RNA-hydrolyzing abzymes (Abzs) from patients with
      different AI diseases. In contrast to RNases and AI RNA-hydrolyzing Abs, rabbit
      RNase IgGs catalyze only the first step of the hydrolysis reaction but cannot
      hydrolyze the formed terminal 2',3'-cyclophosphate. The data indicate that Abzs
      of AI patients hydrolyzing nucleic acids in part may be Abs against RNA and its
      complexes with proteins.

PMID- 18729242
TI  - A survey of the year 2007 literature on applications of isothermal titration
      calorimetry.
AB  - Elucidation of the energetic principles of binding affinity and specificity is a
      central task in many branches of current sciences: biology, medicine,
      pharmacology, chemistry, material sciences, etc. In biomedical research, integral
      approaches combining structural information with in-solution biophysical data
      have proved to be a powerful way toward understanding the physical basis of vital
      cellular phenomena. Isothermal titration calorimetry (ITC) is a valuable
      experimental tool facilitating quantification of the thermodynamic parameters
      that characterize recognition processes involving biomacromolecules. The method
      provides access to all relevant thermodynamic information by performing a few
      experiments. In particular, ITC experiments allow to by-pass tedious and (rarely
      precise) procedures aimed at determining the changes in enthalpy and entropy upon
      binding by van't Hoff analysis. Notwithstanding limitations, ITC has now the
      reputation of being the "gold standard" and ITC data are widely used to validate
      theoretical predictions of thermodynamic parameters, as well as to benchmark the
      results of novel binding assays. In this paper, we discuss several publications
      from 2007 reporting ITC results. The focus is on applications in biologically
      oriented fields. We do not intend a comprehensive coverage of all newly
      accumulated information. Rather, we emphasize work which has captured our
      attention with originality and far-reaching analysis, or else has provided ideas
      for expanding the potential of the method.

PMID- 18729243
TI  - Evaluation of the pharmacotherapeutic efficacy of Garcinia cambogia plus
      Amorphophallus konjac for the treatment of obesity.
AB  - Hydroxycitric acid (HCA), the main compound of Garcinia cambogia extract, is a
      competitive blocker of ATP-citrate-lyase, presenting a potential inhibition of
      fatty acid biosynthesis. Glucomannan fibers, abundant in Amorphophallus konjac,
      seem to reduce the absorption kinetics of dietary fat. Therefore, the aim of this
      double-blind randomized study was to evaluate the pharmacotherapeutic efficacy of
      standardized extracts of G. cambogia (52.4% HCA) plus A. konjac (94.9%
      glucomannan) in the treatment of obesity. Fifty-eight obese subjects (BMI 30.0
      39.9 kg/m(2)) were assigned to the placebo group (n = 26) or the treatment group
      (n = 32); no dietary restrictions were applied. Over a 12-week period, subjects
      were given daily doses of either Garcinia (2.4 g) plus Konjac (1.5 g) or placebo
      prior to their main meals (3 times/day). Before the start of treatment, and every
      4 weeks thereafter, the following were recorded: height, weight, circumferences
      and body composition, resting energy expenditure (REE), lipid profile and glucose
      levels. The treatment had no significant effect on anthropometric parameters,
      REE, triglycerides or glucose levels. However, a significant reduction was
      observed in total cholesterol (-32.0 +/- 35.1 mg/dL) and LDL-c levels (-28.7 +/-
      32.7 mg/dL) in the treated group, the final levels being significantly lower than
      those of the placebo group (p = 0.008 and p = 0.020, respectively). The results
      obtained suggest that the treatment had a significant hypocholesterolemic effect,
      without influencing the anthropometric or calorimetric parameters tested.

PMID- 18729244
TI  - Azadirachta indica modulates carcinogen biotransformation and reduced glutathione
      at peri-initiation phase of benzo(a)pyrene induced murine forestomach
      tumorigenesis.
AB  - The present study evaluated the effects of aqueous Azadirachta indica leaf
      extract (AAILE) on the activities of certain phase I (cytochrome P450, cytochrome
      b(5) and aryl hydrocarbon hydroxylase) as well as phase II (glutathione-S
      transferase and UDP-glucuronosyl transferase) biotransformation enzymes; and
      reduced glutathione (GSH) (in forestomach and hepatic tissues) during/after intra
      gastric instillations of B(a)P in murine forestomach tumorigenesis bioassay
      protocol. The activities of phase I biotransformation enzymes were found to
      increase, whereas a decrease in GSH content as well as glutathione-S-transferase
      was observed in mice receiving only B(a)P during as well as 2 weeks after B(a)P
      instillations. The activity of UDP-glucuronosyltransferase decreased during B(a)P
      instillations, whereas after the latter, the activity increased when compared
      with the control mice. However, in mice that received AAILE along with B(a)P
      instillations, a decrease in phase I enzymes was accompanied by an increase in
      phase II enzymes as well as GSH contents. Only AAILE treatment reduced the
      activities of phase I biotransformation enzymes and enhanced the GSH contents as
      well as the activities of phase II enzymes. Observations of the present study
      seem to be quite significant and (when taken together with our earlier findings)
      provides evidence for A. indica mediated modulation of the peri-initiation phase
      of the process of forestomach tumorigenesis.

PMID- 18729245
TI  - Food supplementation with an olive (Olea europaea L.) leaf extract reduces blood
      pressure in borderline hypertensive monozygotic twins.
AB  - Hypertension is a harmful disease factor that develops unnoticed over time. The
      treatment of hypertension is aimed at an early diagnosis followed by adequate
      lifestyle changes rather than pharmacological treatment. The olive leaf extract
      EFLA943, having antihypertensive actions in rats, was tested as a food supplement
      in an open study including 40 borderline hypertensive monozygotic twins. Twins of
      each pair were assigned to different groups receiving 500 or 1000 mg/day EFLA943
      for 8 weeks, or advice on a favourable lifestyle. Body weight, heart rate, blood
      pressure, glucose and lipids were measured fortnightly. Blood pressure changed
      significantly within pairs, depending on the dose, with mean systolic differences
      of < or =6 mmHg (500 mg vs control) and < or =13 mmHg (1000 vs 500 mg), and
      diastolic differences of < or =5 mmHg. After 8 weeks, mean blood pressure
      remained unchanged from baseline in controls (systolic/diastolic: 133 +/- 5/77 +/
      6 vs 135 +/- 11/80 +/- 7 mmHg) and the low-dose group (136 +/- 7/77 +/- 7 vs 133
      +/- 10/76 +/- 7), but had significantly decreased for the high dose group (137 +/
      10/80 +/- 10 vs 126 +/- 9/76 +/- 6). Cholesterol levels decreased for all
      treatments with significant dose-dependent within-pair differences for LDL
      cholesterol. None of the other parameters showed significant changes or
      consistent trends. Concluding, the study confirmed the antihypertensive and
      cholesterol-lowering action of EFLA943 in humans.

PMID- 18729246
TI  - Inhibition of soluble epoxide hydrolase by extracts derived from inflammation
      treating Chinese medicinal herbs.
AB  - Soluble epoxide hydrolase (sEH) has been proved to be a key enzyme involved in
      inflammation progression, and inhibition of sEH is therefore very helpful or
      crucial for the treatment of inflammation-related diseases. In order to uncover
      new clues suggesting the presence of phytochemical-based sEH inhibitors, and to
      rationalize the utility of the inflammation-treating Chinese medicinal herbs, the
      ethanol extracts derived from 46 medicinal herbs, traditionally used for the
      treatment of inflammation-associated diseases in China, were tested for sEH
      inhibition activity using a recently developed sensitive fluorescence-based
      assay. Screened at 10 microg/mL, four extracts showed substantial inhibitions of
      sEH (inhibition rates >50%). The ethanol extract of Sophora flavescens root
      (Fabaceae) possessed the strongest inhibitory activity against sEH (IC(50): 2.07
      microg/mL). These preliminary findings highlighted the presence of sEH
      inhibitor(s) in the plant kingdom, and the possibility that the inflammation
      treating herbal medicines could be an untapped reservoir for sEH-inhibition
      agents.

PMID- 18729247
TI  - Antibacterial potential of Antarctic lichens against human pathogenic Gram
      positive bacteria.
AB  - Extracts from five Antarctic lichens (L3, Stereocaulon alpinum; L5, Ramalina
      terebrata; L6, Caloplaca sp.; L8, Lecanora sp.; and L17, Caloplaca regalis) were
      tested for antimicrobial activities against several clinically important microbes
      by disk diffusion. The minimum inhibitory concentration (MIC) of each extract was
      determined by a broth dilution method. Extracts from L3, L5, L6 and L8 were
      active against two Gram(+) strains. B. subtilis was more sensitive to lichen
      extracts (except L5) than S. aureus. The MIC of lichen extracts against B.
      subtilis and S. aureus was observed from 36.7 +/- 0.3 to 953.8 +/- 85.8 microg/mL
      and 68.5 +/- 0.6 to >1000 microg/mL, respectively. Comparisons of MIC values of
      Antarctic lichen crude extracts to previously published MIC values of some
      reported lichen metabolites against Gram(+) bacteria indicated that Antarctic
      lichens might be an enriched source of effective antibacterial agents against
      clinically relevant Gram(+) species.

PMID- 18729248
TI  - A one-year survey on the use of a powder from Rosa canina lito in acute
      exacerbations of chronic pain.
AB  - This pilot surveillance included 152 patients with acute exacerbations of chronic
      pain, 124 (Back group) with non-specific low back pain (NSLBP), 20 with NSLBP
      overridden by osteoarthritic pain (Knee-Hip group), and eight with specific LBP
      (included in the safety analysis). Patients were recommended the rose hip and
      seed powder Litozin at a dose providing up to 3 mg of galactolipid/day for up to
      54 weeks. Clinical symptoms and well-being were assessed every 6 weeks. The
      patients also kept a diary of their pain and the requirement for rescue
      medication. Data were analysed by intention to treat with last observation
      carried forward. Only 77 patients completed the year of surveillance.
      Multivariate analysis suggested an appreciable overall improvement during the
      surveillance, irrespective of group, and this was reflected for most of the
      individual measures in repeated measures ANOVA. The degree and time-course of
      improvement echoed that seen in similar surveillances of patients receiving an
      aqueous extract of Harpagophytum. Multiple regression analyses indicated that
      percentage changes from baseline tended to be greater in patients with greater
      degrees of pain and disability, but were otherwise largely unrelated to the
      patients' characteristics. There were no serious adverse events. The rose hip and
      seed powder, Litozin, seems to deserve further, more definitive studies as a
      possible option in long-term management of NSLBP with or without osteoarthritic
      pain.

PMID- 18729249
TI  - Chemoprotective effects of a protein from the red algae Porphyra yezoensis on
      acetaminophen-induced liver injury in rats.
AB  - Seaweeds contribute to the maintenance of health through their nutritional and
      medicinal properties. The effects of PYP, a 14 kDa protein isolated from a hot
      water extract of the marine alga Porphyra yezoensis, on AAP-induced liver injury
      in rats was evaluated. AAP induced acute liver injury and AAP-induced
      hepatotoxicity is the leading cause of liver failure. In this study, male Sprague
      Dawley rats were assigned to one of three treatment groups: control, AAP, or AAP
      + PYP. Compared with the control group, liver tissue from the AAP group showed
      increased levels of caspase-3 activity and DNA fragmentation, decreased levels of
      GSH and increased serum GOT/GPT levels. In contrast, treatment with AAP + PYP
      produced levels of caspase-3 activity, DNA fragmentation, GSH and GOT/GPT that
      matched the values seen in the control group. It is concluded that PYP may
      prevent AAP-induced liver injury.

PMID- 18729251
TI  - Phytotherapeutic prevention of dental biofilm formation.
AB  - The antimicrobial and biofilm formation preventive properties of Mentha piperita
      and Rosmarinus officinalis essential oils and chlorhexidine were assessed against
      Streptococcus mutans and Streptococcus pyogenes. 26 and 20 compounds were
      identified by GC and GC-MS analysis in hydrodistilled oils from M. piperita and
      R. officinalis, respectively. The minimal bactericidal concentrations (MBC) of
      the M. piperita and R. officinalis oils and chlorhexidine were (6000, 2000, 8000
      ppm) and (1000, 4000, 1000 ppm) for S. mutans and S. pyogenes, respectively. The
      decimal reduction time (D) of S. mutans exposed to the oils at their MBC levels
      was 2.8 min while chlorhexidine showed a longer time. The D values of S. pyogenes
      on exposure to the MBC levels of M. piperita and R. officinalis oils and of
      chlorhexidine were 2.14, 4.28 and 2.8 min, indicating a higher efficacy of M.
      piperita oil. Biofilm formation was performed by growing S. mutans culture with
      and without essential oils in LB medium in polystyrene tubes. In vitro biofilm
      inhibitory properties were in the order M. piperita > R. officinalis >
      chlorhexidine. In vivo experiments on the antibiofilm properties revealed that
      all concentrations of the oils were significantly (p < 0.001) more effective than
      chlorhexidine. In conclusion, essential oils may be considered as safe agents in
      the development of novel antibiofilm agents.

PMID- 18729252
TI  - The effect of the aqueous extract of the roots of Asparagus racemosus on
      hepatocarcinogenesis initiated by diethylnitrosamine.
AB  - Histopathological studies of the hepatic tissues of Wistar rats treated with
      diethylnitrosamine (DEN) (200 mg/kg b wt, i.p.) once a week for 2 weeks, followed
      by treatment with DDT, a tumor promoter (0.05% in diet) for 2 weeks and kept
      under observation for another 18 weeks, demonstrated the development of
      malignancy. Pretreatment of Wistar rats with the aqueous extract of the roots of
      Asparagus racemosus prevented the incidence of hepatocarcinogenesis.
      Immunohistochemical staining of the hepatic tissues of rats treated with DEN
      showed the presence of p53+ foci (clusters of cells expressing the mutated p53
      protein), whereas an absence of p53+ foci was observed in Wistar rats pretreated
      with the aqueous extract of the roots of Asparagus racemosus. The microsections
      of the hepatic tissue of rats treated with DEN followed by treatment with the
      aqueous extract of Asparagus racemosus showed an absence of p53+ foci. The
      results of the biochemical determinations also show that pretreatment of Wistar
      rats with the aqueous extract of Asparagus racemosus leads to the amelioration of
      oxidative stress and hepatotoxicity brought about by treatment with DEN. These
      results prove that the aqueous extract of the roots of Asparagus racemosus has
      the potential to act as an effective formulation to prevent hepatocarcinogenesis
      induced by treatment with DEN.

PMID- 18729253
TI  - Effect of seabuckthorn (Hippophae rhamnoides) leaf aqueous and ethanol extracts
      on avoidance learning during stressful endurance performance of rats: a dose
      dependent study.
AB  - Aqueous and 70% ethanol extracts of seabuckthorn (Hippophae rhamnoides L.,
      Elaeagnaceae) dry leaves were examined in rats for their dose dependent effect on
      active avoidance learning, if any. Avoidance learning was studied during
      endurance performance in multiple stressful environments consisting of light,
      noise and electric shock (10 mV) by using Runimex, a circular runway animal
      model. Neither of the evaluated extracts showed activity in rats to enhance
      cognitive functions with reference to avoidance learning during exposure to
      stressful conditions of multiple stressors. But both extracts were found to
      possess physical performance enhancing activity during the studied stressful
      conditions.

PMID- 18729255
TI  - Flavonoids, taxifolin and luteolin attenuate cellular melanogenesis despite
      increasing tyrosinase protein levels.
AB  - Flavonoids are a group of polyphenolic compounds widely distributed in plants.
      Their potent bio-activities and relatively low toxicity have rendered them useful
      ingredients in functional cosmetics. The purpose of the present study was to
      examine their potential effects on cellular melanogenesis. When tested in murine
      melanoma B16F10 cells activated by alpha-melanocyte stimulating hormone (alpha
      MSH), taxifolin and luteolin inhibited the cellular melanogenesis as effectively
      as arbutin, one of the most widely used hypopigmenting agents in cosmetics. As
      opposed to their antimelanogenic effects, taxifolin and luteolin rather increased
      the tyrosinase protein levels in the absence and presence of alpha-MSH. However,
      these flavonoids effectively inhibited tyrosinase-catalysed oxidation of l
      dihydroxyphenylalanine in cell-free extracts and in living cells. Furthermore,
      they attenuated cell pigmentation induced by expression of exogenous human
      tyrosinase. Therefore, the antimelanogenic effects of taxifolin and luteolin are
      attributed to their inhibitory effects on tyrosinase enzymatic activity, despite
      their effects on increasing tyrosinase protein levels.

PMID- 18729254
TI  - Effect of Terminalia arjuna extract on adriamycin-induced DNA damage.
AB  - The effect of a bark extract of Terminalia arjuna (TAE) was studied on the
      alteration of adriamycin (ADR)-induced micronuclei formation in cultured human
      peripheral blood lymphocytes. Exposure of lymphocytes to ADR resulted in a dose
      dependent increase in the micronuclei formation indicating DNA damage.
      Pretreatment of lymphocytes with TAE before ADR treatment resulted in a
      significant decline in micronuclei formation. Increasing doses of ADR caused a
      dose-dependent increase in the frequency of lymphocytes bearing one, two and
      multiple micronuclei. Prior exposure of lymphocytes to 15 microg/mL of TAE
      significantly reduced the frequency of lymphocytes bearing one, two and multiple
      micronuclei when compared with ADR-treated control. TAE-inhibited the induction
      of (*)OH (hydroxyl), O2(*-) (superoxide), DPPH (1,1-diphenyl-2-picrylhydrazyl),
      ABTS(*+) (2,2-azino-bis-3-ethyl benzothiazoline-6-sulphonic acid) radicals in a
      dose-dependent manner. These results demonstrate that TAE protects DNA against
      ADR-induced damage.

PMID- 18729256
TI  - Comparison of the antidiabetic activity of Berberis lyceum root extract and
      berberine in alloxan-induced diabetic rats.
AB  - Berberine has been shown to have hypoglycaemic activity in several in vitro and
      in vivo models, although the mechanism of action is not fully known. Berberis
      lyceum Royle root produces high concentrations of berberine, and in traditional
      medicine, the whole extract of this plant is used widely to treat diabetes. The
      antidiabetic activity of the ethanol root extract of Berberis lyceum was compared
      with pure berberine in normal and alloxan-diabetic rats using similar doses of
      each. The concentration of berberine in the extract was determined to be 80% dry
      weight with only trace amounts of other alkaloids present. The purpose of the
      study was to investigate the effects of berberine and a whole extract of Berberis
      lyceum on blood glucose and other parameters associated with diabetes, to compare
      the effects of the crude extract with those of pure berberine and thus validate
      its use as a therapeutic agent, and finally to identify any contribution of the
      other components of the extract to these effects. Oral administration of 50 mg/kg
      of Berberis extract and berberine to normal and experimental diabetic rats
      produced a significant (p < 0.05) reduction in blood glucose levels from days 3-7
      days of treatment. Significant effects were also observed on the glucose
      tolerance, glycosylated haemoglobin, serum lipid profiles and body weight of
      experimental animals. Berberis extract and berberine demonstrated similar effects
      on all parameters measured, and although the extract was comparable in efficacy
      to berberine, it did not produce any effects additional to those shown by pure
      berberine. The results support the use of the extract in traditional medicine,
      and demonstrate that apart from being a highly cost-effective means of treating
      with berberine, the total extract does not appear to confer any additional
      benefits or disadvantages compared with the pure compound.

PMID- 18729257
TI  - Antioxidant activity of flavonoids in isolated mitochondria.
AB  - Mitochondria are important intracellular sources and targets of reactive oxygen
      species (ROS), while flavonoids, a large group of secondary plant metabolites,
      are important antioxidants. Following our previous study on the energetics of
      mitochondria exposed to the flavonoids quercetin, taxifolin, catechin and
      galangin, the present work addressed the antioxidant activity of these compounds
      (1-50 micromol/L) on Fe(2+)/citrate-mediated membrane lipid peroxidation (LPO) in
      isolated rat liver mitochondria, running in parallel studies of their antioxidant
      activity in non-organelle systems. Only quercetin inhibited the respiratory chain
      of mitochondria and only galangin caused uncoupling. Quercetin and galangin were
      far more potent than taxifolin and catechin in affording protection against LPO
      (IC(50) = 1.23 +/- 0.27 and 2.39 +/- 0.79 micromol/L, respectively), although
      only quercetin was an effective scavenger of both 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) and superoxide radicals. These results, together with the previous study,
      suggest that the 2,3-double bond in conjugation with the 4-oxo function in the
      flavonoid structure are major determinants of the antioxidant activity of
      flavonoids in mitochondria, the presence of an o-di-OH structure on the B-ring,
      as occurs in quercetin, favours this activity via superoxide scavenging, while
      the absence of this structural feature in galangin, favours it via a decrease in
      membrane fluidity and/or mitochondrial uncoupling.

PMID- 18729258
TI  - Comparison of the therapeutic effects of different compositions of muskone in the
      treatment of experimental myocardial infarct in rats and analgesia in mice.
AB  - The aim of this study was to compare the therapeutic effects of muskone, a
      traditional preparation containing slender Dutchmanspipe root (MCS) used to treat
      angina pectoris and related conditions, muskone containing inula root (MCI) in
      place of MCS, and muskone (M) without either slender Dutchmanspipe root (S) or
      inula root (I) on acute myocardial infarct (AMI) in rats and the pain response in
      mice. The AMI model was established by ligating the left anterior descending
      coronary artery (LAD). The AMI rats were treated with MCS, MCI, M, S and I,
      respectively, before the surgical operation. Plasma endothelin (ET), 6-keto
      prostaglandin F(1alpha) (6-keto-PGF(1alpha)), thromboxane (TXB(2)) and myocardial
      apoptosis were detected, the ratio of 6-keto-PGF(1alpha) level to TXB(2) level (6
      keto-PGF(2alpha)/TXB(2)) was calculated, and the infarct size was determined. In
      the pain relieving study, the prophylactic treatments with MCS, MCI, M, S, I and
      aspirin were administered to the mice once a day for 5 days, the response latency
      and the number of abdominal contractions after the stimulus of intraperitoneal
      injection of acetic acid were recorded. The results show that MCS, MCI and M
      significantly ameliorated plasma ET, TXB(2), 6-keto-PGF(1alpha) and 6-keto
      PGF(2alpha)/TXB(2) levels, reduced infarct size and opposed myocardial apoptosis.
      Simultaneously, they also significantly reduced the abdominal contractions and
      also prolonged the response latency induced by acetic acid in the mice. S and I
      only showed a degree of relieving pain, but their efficacy was weaker than that
      of MCS, MCI and M, and they had little cardioprotective effect. In conclusion,
      MCS, MCI and M had a significant cardioprotective and analgesic effect, and they
      had similar efficacy. S and I only had a secondary analgesic effect. Removing S
      from the MCS or replacing S with I did not influence the cardioprotective effect
      and analgesic effect.

PMID- 18729259
TI  - Prenatal diagnosis of right pulmonary artery to left atrium communication.
AB  - We report a case of right pulmonary artery to left atrium communication in a
      fetus at 24 weeks' gestation. Fetal echocardiography showed dilatation of the
      left atrium and main and right pulmonary arteries. The right pulmonary artery was
      seen to communicate with the left atrium. Color Doppler velocimetry demonstrated
      high-velocity flow through the communication. The pregnancy was terminated and
      findings were confirmed at autopsy. The embryological and postnatal aspects of
      right pulmonary artery to left atrium communication are discussed.

PMID- 18729260
TI  - Ultrasonographic visualization of balloon placement for uterine tamponade in
      massive primary postpartum hemorrhage.
AB  - This case report is the first documentation of ultrasonographic confirmation of
      positioning of a Sengstaken-Blakemore balloon catheter (SBEC) in the management
      of massive postpartum hemorrhage. The sonongraphic position, while incorrect
      according to conventional use of uterine balloon catheters, raises the
      possibility of an alternative mechanism of action of the balloon: not uterine
      cavity tamponade but hydrostatic pressure directly around the uterine arteries, a
      mechanism akin to mechanical uterine artery embolization or ligation. If this
      hypothesis is correct, it not only elucidates how balloon tamponade works but
      also challenges current thinking on how postpartum hemorrhage should be managed
      effectively. Future studies are required to corroborate this hypothesis and we
      believe that sonographic confirmation of balloon catheter location should be an
      integral part of uterine balloon tamponade in women with massive primary
      postpartum hemorrhage.

PMID- 18729261
TI  - [The short history of protein kinase inhibitors. New, competitive, successful].

PMID- 18729262
TI  - [Protein tyrosine kinases as drug targets. An important group of intracellular
      regulators].

PMID- 18729263
TI  - [Medical chemistry and molecular mechanisms of tyrosine kinase inhibitors. The
      viewpoint of pharmaceutical research].

PMID- 18729264
TI  - [Development of tyrosine kinase inhibitors for hematologic neoplasms. FLT3 and
      JAK2 as therapeutic targets].

PMID- 18729265
TI  - [Innovations with system disrupting potential? New drugs of high value].

PMID- 18729267
TI  - [Statement from the DPhG: DPhG opinion on the proposed health claims regulation].

PMID- 18729268
TI  - [Statement of the DPhG: Opinion of the DPhG of the draft of a Law on genetic
      studies in humans (genetic diagnosis)].

PMID- 18729270
TI  - [Inhibition of the VEGF receptor system with tyrosine kinase inhibitors.
      Angiogenesis inhibition in oncology].

PMID- 18729273
TI  - [Wall pellitory--an unrecognized plant allergy in Central Europe].

PMID- 18729281
TI  - [Pharmazie in unserer Zeit 5/2008].

PMID- 18729283
TI  - [Enzyme replacement therapy for Gaucher's Disease].

PMID- 18729284
TI  - [ROR-alpha--a potential target against overweight?].

PMID- 18729285
TI  - [New therapeutic approaches in cystic fibrosis].

PMID- 18729286
TI  - [Don't stop me now!].

PMID- 18729291
TI  - Synthesis and characterization of a long, rigid photoswitchable cross-linker for
      promoting peptide and protein conformational change.
AB  - Azobenzene-based photoswitchable compounds can be use to photocontrol a variety
      of biochemical systems. In some cases, their effectiveness may be limited by the
      size of the conformational change that the switch undergoes. To produce an
      azobenzene photoswitch that undergoes a large end-to-end distance change upon
      isomerization, we synthesized 3,3'-diazene-1,2-diylbis{6-[2-sulfonato-4
      (chloroacetylamino)phenylethynyl]benzene sulfonic acid} (DDPBA). This long,
      rigid, water-soluble, thiol-reactive cross-linker undergoes an end-to-end
      distance change of approximately 13 A upon isomerization. DDPBA was successfully
      cross-linked to peptides through cysteine side chains. The photoswitch undergoes
      trans-to-cis photoisomerization maximally when irradiated at 400 nm, although the
      efficiency of production of the cis isomer is lower than for simpler azobenzenes.
      Under steady-state illumination conditions, the percentage of cis form produced
      increases as temperature increases; approximately 56 % cis is obtained at 60
      degrees C. Thermal relaxation occurs with a half-life of approximately 75 min at
      room temperature. When DDPBA was attached to an alpha-helical peptide with two
      cysteine residues at i and i+14 positions, an increase in helix content was
      observed after photoirradiation. When cross-linked to another peptide with two
      cysteine residues spaced at i and i+21 positions, a decrease in helix content
      after trans-to-cis isomerization was observed. Due to the small percentage of cis
      form produced under the experimental conditions, the CD signal changes were
      small. However, the large structural change upon photoisomerization provided by
      this cross-linker can potentially be used to photoswitch other biochemical
      systems.

PMID- 18729292
TI  - Prognosis of neonates in pregnant women with systemic lupus erythematosus.
AB  - PURPOSE: The effects of maternal systemic lupus erythematosus (SLE) on neonatal
      prognosis were examined by comparing clinical features of full-term babies born
      to lupus mothers and age- and parity-matched controls. PATIENTS AND METHODS: From
      January 2000 to December 2005, 39 singletons were born to 37 SLE women. Excluding
      11 cases of prematurity and preeclampsia, 28 full-term neonates formed the lupus
      group. The control group included 66 full-term babies. The retrospective study
      examined medical records and compared gestational age, birth weight, days of
      hospital stay, small for gestational age (SGA) frequency, Apgar scores < 7, and
      parity. Lupus neonates were tested for anti-nuclear antibody (ANA) and platelet
      count, and electrocardiogram was performed. RESULTS: Average gestational age (38
      vs. 39 weeks, p < 0.05) and birth weight (2,775 vs. 3,263g, p < 0.05) were
      significantly different between the SLE and control groups. SGA frequency was
      higher in the SLE group (25% vs. 4.5%, p < 0.05). No significant difference was
      observed in Apgar score, birth weight, gestational age, SGA frequency, and
      platelet count between lupus subgroups formed based on anti-dsDNA antibody levels
      and antiphospholipid antibody status. CONCLUSION: The association of maternal
      ANAs, antiphospholipid antibodies, and drug history with neonatal prognosis could
      not be elucidated. However, even in uncomplicated pregnancies, maternal lupus is
      disadvantageous for gestational age, birth weight, and SGA frequency.

PMID- 18729293
TI  - Effect of allergic rhinitis on the use and cost of health services by children
      with asthma.
AB  - PURPOSE: Allergic rhinitis (AR) is common among children with asthma and
      exacerbates asthma symptoms. To assess the incremental utilization and cost of
      asthma-related health services due to concomitant AR among asthmatic children.
      MATERIALS AND METHODS: Asthma-related claims were extracted from the Korean
      National Health Insurance (NHI) claims database, which covers 97% of the
      population. Per-capita utilization and costs of asthma-related services were
      determined from the societal perspective. RESULTS: Of 319,714 children (1-14
      years old) with chronic asthma in 2003, 195,026 had concomitant AR (prevalence
      610 per 1,000 asthmatic children). Children with AR had 1.14 times more
      outpatient visits, 1.30 times more emergency department (ED) visits, and 1.49
      times more hospitalizations than children without AR. More children with AR used
      general hospitals (7.17%) than children without AR (3.23%). The ratios of unit
      pharmaceutical costs per outpatient visit, ED visit, and admission between
      children with and without AR were 1.27, 1.20, and 1.14. Total annual expenditure
      combining direct health care, transportation, and caregivers' costs, were $273
      and $217 for children with and without AR, respectively. CONCLUSION: Health
      service utilization and costs for asthma were greater for asthmatic children with
      AR. More frequent ED visits and admissions among asthmatic children with AR
      suggest poorer control and more frequent exacerbations. Higher unit cost of
      pharmaceuticals during visits, tendency to receive asthma care from a higher
      level facility, and greater risk of ED visit or admission all contributed to the
      additional economic burden of AR.

PMID- 18729294
TI  - Risk factors for neonatal infections in full-term babies in South Korea.
AB  - PURPOSE: Since 1997, private postnatal care facilities (San-hu-jo-ri-won in
      Korean) have emerged to take the role of the family. As a result, neonates are
      now exposed to many people and are very vulnerable to infection. However, there
      has been no study on the influence of postnatal care facilities on neonatal
      infection. The aim of this study was to determine the risk factors of neonatal
      infection in full-term babies in Korea. MATERIALS AND METHODS: We followed up 556
      pregnant women and their babies for 4 weeks after their births at 2 hospitals in
      Seoul and Daejeon from October 2004 to September 2005. Among 512 full-term
      babies, 58 had infectious diseases. To determine the risk factors for infection,
      53 infected neonates at 4-28 days of life and 413 healthy neonates were compared.
      RESULTS: The incidence of neonatal infection at 4 to 28 days after birth was
      10.5%. After adjusting the related factors, the number of siblings (OR = 2.05,
      95% CI = 1.13-3.71 for 1 or more) and postnatal care facilities or home aides (OR
      = 1.91, 95% CI = 1.07-3.45) were significant risk factors. Formula or mixed
      feeding (OR = 1.66, 95% CI = 0.91-3.04) increased the risk of neonatal infection
      but it was not statistically significant. CONCLUSION: When the newborns had
      siblings, stayed at postnatal care facilities, or were cared for by home aides,
      the risk of neonatal infections significantly increased. Further research on the
      feeding effect on neonatal infection and evaluation of prevention efforts are
      needed.

PMID- 18729295
TI  - Comparison of in-house PCR with conventional techniques and Cobas Amplicor M.
      tuberculosis kit for detection of Mycobacterium tuberculosis.
AB  - PURPOSE: Polymerase chain reaction (PCR) assay, introduced as a fast and
      sensitive diagnostic method, is useful in detecting Mycobacterium tuberculosis.
      The purpose of this study was to evaluate the usefulness of in-house PCR assay in
      the detection of Mycobacterium tuberculosis by comparing PCR results with
      conventional diagnostic techniques and Cobas Amplicor M. tuberculosis kit.
      MATERIALS AND METHODS: We retrospectively assessed the diagnostic yield of in
      house PCR method employed for the amplification IS6110 sequences in 2,973
      specimens. We also compared in-house PCR with Cobas Amplicor M. tuberculosis kit
      in 120 specimens collected from June to July 2006. Routine acid-fast stain (AFS)
      and culture assay were also performed and analyzed. RESULTS: Of 2,973 cases,
      2,832 cases (95.3%) showed consistent results between in house PCR, AFS and
      culture methods, whereas 141 (4.7%) displayed inconsistent results. The
      sensitivities, specificities, and positive and negative predictive values of each
      method were as follows: 77.5%, 99.7%, 95.5%, and 98.0%, respectively for PCR;
      49.2%, 100%, 100%, and 95.7%, respectively, for AFS method; and 80.7%, 100%,
      100%, and 98.3%, respectively, for culture assay. Consistent results between PCR
      and Cobas Amplicor M. tuberculosis kit were shown in 109 cases (90.8%). The
      sensitivities, specificities, and positive and negative predictive values of each
      method were as follows: 81.3%, 98.9%, 96.3%, and 93.5% respectively for PCR and
      71.9%, 100%, 100%, and 90.7%, respectively, for Cobas Amplicor kit. CONCLUSION:
      In-house PCR and Cobas Amplicor kit show high sensitivity and specificity, and
      are reliable tests in the diagnosis of tuberculosis.

PMID- 18729296
TI  - Is electrical stimulation beneficial for improving the paralytic effect of
      botulinum toxin type A in children with spastic diplegic cerebral palsy?
AB  - PURPOSE: The purpose of the present study was to investigate whether electrical
      stimulation (ES) improves the paralytic effect of botulinum toxin type A (BTX-A)
      and evaluate the differences between low frequency (LF) and high frequency (HF)
      ES in children with spastic diplegic cerebral palsy (CP). MATERIALS AND METHODS:
      Twenty-three children with spastic diplegia CP who had BTX-A injections into both
      gastrocnemius muscles were assessed. Following the toxin injection, electrical
      stimulation was given to 1 side of the injected muscles and a sham-stimulation to
      the other side for 30 min a day for 7 consecutive days [HFES (25Hz) to 11
      children, LFES (4Hz) to 12 children]. The compound motor action potentials (CMAP)
      from the gastrocnemius muscle were assessed before injection and at 5 time points
      (days 3, 7, 14, 21, and 30) after injection. The clinical assessments of
      spasticity were performed before and 30 days after injection. RESULTS: The CMAP
      area became significantly lower in both LFES and HFES sides from 3 days after
      injection compared to baseline values. In other words, the CMAP area of the sham
      stimulated side showed a significant decrease at 7 or 14 days after injection.
      However, there were no significant differences in clinical assessment of
      spasticity between the stimulated and sham-stimulated sides. CONCLUSION: Short
      term ES in both LF and HF to the spastic muscles injected with BTX-A might induce
      earlier denervating action of BTX-A. However, it does not necessarily lead to
      clinical and electrophysiological benefits in terms of reduction of spasticity.

PMID- 18729297
TI  - Antenatal cognitive-behavioral therapy for prevention of postpartum depression: a
      pilot study.
AB  - PURPOSE: To examine the efficacy of cognitive-behavioral therapy (CBT) for the
      prevention of postpartum depression (PPD) in "at risk" women. MATERIALS AND
      METHODS: We recruited 927 pregnant women in 6 obstetric and gynecology clinics
      and screened them using Beck Depression Inventory (BDI). Ninety-nine of the
      screened women who had significantly high scores in BDI (a score above 16) were
      selected for the study. They were contacted through by telephone, and 27 who had
      consented to participate in the study were interviewed via SCID-IV-I. Twenty
      seven eligible women were randomly assigned to the CBT intervention (n = 15) and
      control condition (n = 12). All participants were required to complete written
      questionnaires, assessing demographic characteristics, depressive symptoms,
      negative thoughts, dyadic communication satisfaction, and global marital
      satisfaction prior to treatment and approximately 1 month postpartum. The 15
      women in the CBT condition received 9 bi-weekly 1-hour individual CBT sessions,
      targeting and modifying negative patterns of thinking and behaviors occurring in
      the context of the dyadic relationship. RESULTS: The analysis of covariance
      (ANCOVA) showed that there were significant differences in all postpartum
      measures between the 2 groups, indicating that our antenatal intervention with
      CBT was effective in reducing depressive symptoms and improving marital
      satisfaction, which lasted until the postpartum period. CONCLUSION: Our pilot
      study has provided preliminary empirical evidence that antenatal CBT intervention
      can be an effective preventive treatment for PPD. Further study in this direction
      was suggested.

PMID- 18729298
TI  - The prevalence of the metabolic syndrome in Korean children and adolescents:
      comparisons of the criteria of Cook et al., Cruz and Goran, and ferranti et al.
AB  - PURPOSE: Although the metabolic syndrome (MS), which can lead to the development
      of cardiovascular disease (CVD) or diabetes mellitus (DM), is increasing in
      children and adolescents, no unified criteria have been established, and little
      attention has been paid to its occurrence in Korean children and adolescents. In
      this study, we compared the prevalence of the MS in Korean children and
      adolescents using the criteria which were modified for children and adolescents
      by Cook et al., Cruz and Goran, and Ferranti et al. MATERIALS AND METHODS: The
      study population was a nationwide representative sample of 3,431 children and
      adolescents (1,828 boys and 1,603 girls) from the 2001 Korean National Health and
      Nutrition Examination Survey (KNHANES), who were aged 10-19 years (mean 14.1 +/-
      2.8), underwent a physical examination, and fasted for 8 hours before collecting
      blood samples. RESULTS: The rates of the MS were 6.1, 5.3, and 14.0% according to
      the criteria of Cruz and Goran, Cook et al., and Ferranti et al., respectively,
      and the agreement rate of the three sets of criteria was 88.7%. CONCLUSION:
      Unified criteria for the MS and a strategy for reducing obesity in children and
      adolescents will be necessary to prevent the occurrence of this syndrome.

PMID- 18729299
TI  - Maternal depression predicts maternal use of corporal punishment in children with
      attention-deficit/hyperactivity disorder.
AB  - PURPOSE: We sought to determine if maternal depression contributed to the use of
      corporal punishment in children with attention-deficit/hyperactivity disorder
      (ADHD). PATIENTS AND METHODS: The data were gathered through chart review of
      clinic-referred children with ADHD and their mothers who were evaluated at a
      psychiatric clinic located in a large academic medical center in Seoul, Korea.
      Daily records kept by parents and 13 items from the Physical Assault of the
      Parent-Child Conflict Tactics Scales (CTSPC) were used to assess corporal
      punishment. Ninety-one children with ADHD and their mothers were included in this
      study. RESULTS: Mothers who used corporal punishment showed significantly higher
      scores on the Beck Depression Inventory (t = -2.952, df = 89, p < 0.01) than
      mothers who did not. Moreover, maternal depression contributed to the use of
      corporal punishment in ADHD children (Nagelkerke R2 = 0.102, p < 0.05).
      CONCLUSION: Maternal depression contributes to the use of corporal punishment
      with children with ADHD. Assessment and management of the maternal depression
      should be an important focus of evaluation of children with ADHD.

PMID- 18729300
TI  - Numerical simulation of the effect of sodium profile on cardiovascular response
      to hemodialysis.
AB  - PURPOSE: We developed a numerical model that predicts cardiovascular system
      response to hemodialysis, focusing on the effect of sodium profile during
      treatment. MATERIALS AND METHODS: The model consists of a 2-compartment solute
      kinetics model, 3-compartment body fluid model, and 12-lumped-parameter
      representation of the cardiovascular circulation model connected to set-point
      models of the arterial baroreflexes. The solute kinetics model includes the
      dynamics of solutes in the intracellular and extracellular pools and a fluid
      balance model for the intracellular, interstitial, and plasma volumes.
      Perturbation due to hemodialysis treatment induces a pressure change in the blood
      vessels and the arterial baroreceptors then trigger control mechanisms
      (autoregulation system). These in turn alter heart rate, systemic arterial
      resistance, and cardiac contractility. The model parameters are based largely on
      the reported values. RESULTS: We present the results obtained by numerical
      simulations of cardiovascular response during hemodialysis with 3 different
      dialysate sodium concentration profiles. In each case, dialysate sodium
      concentration profile was first calculated using an inverse algorithm according
      to plasma sodium concentration profiles, and then the percentage changes in each
      compartment pressure, heart rate, and systolic ventricular compliance and
      systemic arterial resistance during hemodialysis were determined. A plasma
      concentration with an upward convex curve profile produced a cardiovascular
      response more stable than linear or downward convex curves. CONCLUSION: By
      conducting numerical tests of dialysis/cardiovascular models for various
      treatment profiles and creating a database from the results, it should be
      possible to estimate an optimal sodium profile for each patient.

PMID- 18729301
TI  - The inhibition of insulin-stimulated proliferation of vascular smooth muscle
      cells by rosiglitazone is mediated by the Akt-mTOR-P70S6K pathway.
AB  - PURPOSE: Thiazolidinediones (TZDs) are known to inhibit the proliferation of
      vascular smooth muscle cell (VSMC) by increasing the activity of p27Kip1 and
      retinoblastoma protein (RB). However, the upstream signaling mechanisms
      associated with this pathway have not been elucidated. The Akt-mTOR-P70S6 kinase
      pathway is the central regulator of cell growth and proliferation, and increases
      cell proliferation by inhibiting the activities of p27Kip1 and retinoblastoma
      protein (RB). Therefore, we hypothesized in this study that rosiglitazone
      inhibits VSMC proliferation through the inhibition of the Akt-TOR-P70S6K
      signaling pathway. MATERIALS AND METHODS: Rat aortic smooth muscle cells
      (RAoSMCs) were treated with 10microM of rosiglitazone 24 hours before the
      addition of insulin as a mitogenic stimulus. Western blot analysis was performed
      to determine the inhibitory effect of rosiglitazone treatment on the Akt-mTOR
      P70S6K signaling pathway. Carotid balloon injury was also performed in Otsuka
      Long-Evans Tokushima Fatty (OLETF) diabetic rats that were pretreated with 3
      mg/kg of rosiglitazone. RESULTS: Western blot analysis demonstrated significant
      inhibition of activation of p-Akt, p-m-TOR, and p-p70S6K in cells treated with
      rosiglitazone. The inhibition of the activation of the p-mTOR-p-p70S6K pathway
      seemed to be mediated by both the upstream PI3K pathway and MEK-ERK complex.
      CONCLUSION: The inhibitory effect of rosiglitazone on RAoSMC proliferation in
      vitro and in vivo is mediated by the inhibition of the Akt-mTOR-P70S6K pathway.

PMID- 18729302
TI  - Primary systemic anaplastic large cell lymphoma in Korean adults: 11 years'
      experience at Asan Medical Center.
AB  - PURPOSE: Anaplastic large cell lymphoma (ALCL), a CD30+ T-cell non-Hodgkin's
      lymphoma, represents only 2-8% of lymphoma overall. Information on the clinical
      findings of primary systemic ALCL in Korea is limited. Our aims were to report
      the clinical features and outcomes of primary systemic ALCL. PATIENTS AND
      METHODS: We retrospectively reviewed the medical records of 36 adult patients
      diagnosed with primary systemic ALCL at Asan Medical Center from February 1995
      through June 2006. RESULTS: Of 36 patients, 29 were male. The median age was 39
      years (range, 17-67 years), and 26 (72%) presented with Ann Arbor stages III and
      IV. The most commonly involved extranodal sites were bone (n = 7) and soft tissue
      (n = 6). Thirty-two of all patients (89%) were treated with an anthracycline
      based regimen including cyclophosphamide/doxorubicin/vincristine/prednisone
      (CHOP) as induction chemotherapy; 16 (50%) achieved complete remission (CR), and
      13 (41%) achieved partial remission (PR). Median overall survival (OS) and event
      free survival (EFS) were 49 and 17 months, respectively. Univariate analysis
      showed that performance status (p = 0.035), international prognostic index (IPI)
      (p = 0.025), and age-adjusted IPI (p = 0.034) were significant prognostic factors
      for OS, whereas anaplastic lymphoma kinase (ALK) expression did not affect OS (p
      = 0.483). CONCLUSION: Our retrospective analysis of Korean primary systemic ALCL
      patients showed that median OS was 49 months and overall response to CHOP was
      91%. Performance, IPI, and age-adjusted IPI were predictors of OS, whereas ALK
      expression did not have prognostic significance.

PMID- 18729303
TI  - Vocal analysis related to changes in frequency of pure tone auditory feedback.
AB  - PURPOSE: Many studies have shown that subjects show a change of vocal fundamental
      frequency (F0) when phonating subjects hear their vocal pitch feedback shifted
      upward or downward. This study was performed to demonstrate whether vocal
      parameters [F0, intensity, jitter, shimmer, and noise to harmonic ratio (NHR)] in
      normal males respond to changes in frequency of pure tone masking. MATERIALS AND
      METHODS: Twenty healthy male subjects participated in this study. Subjects
      vocalized /a/ vowel sounds while listening to a pitch- shift pure tone through
      headphones (upward pitch-shift in succession: 1 kHz to 2 kHz and 1 kHz to 4 kHz
      at 50 dB or 80 dB, respectively, downward pitch-shift in succession: 1 kHz to 250
      Hz and 1 kH to 500 Hz at 50 dB or 80 dB, respectively). RESULTS: Vocal intensity,
      F0, was increased, whereas jitter was decreased as the pitch of pure tone was
      shifted upward. However, there was no correlation between shimmer and NHR with
      pitch-shift feedback for pure tones. Unlike vocal pitch- shift feedback in other
      studies, upward pitch-shift feedback of pure tones caused the vocal F0 and
      intensity to change in the same direction as pitch-shift. CONCLUSION: The results
      of this study demonstrated that auditory kinesthetic feedback is affected by
      pitch-shift in pure tone.

PMID- 18729304
TI  - Endobronchial tuberculosis presenting as right middle lobe syndrome: clinical
      characteristics and bronchoscopic findings in 22 cases.
AB  - PURPOSE: Endobronchial tuberculosis (EBTB) presenting as right middle lobe
      syndrome (RMLS) is an uncommon clinical condition. We investigated the clinical
      characteristics in patients with EBTB presenting as RMLS. PATIENTS AND METHODS:
      We retrospectively reviewed the records of 22 patients with EBTB presenting as
      RMLS who were diagnosed at our hospital from 2003 to 2006. RESULTS: Its
      occurrence was more common in females than males (F, 18; M, 4). The mean age was
      70.3 +/- 8.5 years, and 17 patients were above the age of 65 years. Cough with
      sputum was the most common manifestation and 2 patients were asymptomatic. In
      bronchoscopic analysis, the most common finding was edematous-type EBTB, which
      was found in 15 patients, followed by actively caseating type in 6 and tumorous
      type in 1. Acid-fast bacilli (AFB) staining for bronchial washing fluid was
      positive in only 5 patients: 1 with edematous type and 4 with actively caseating
      type. Bronchoscopic biopsy showed chronic granulomatous inflammation in 16
      patients. Follow-up chest X-ray after treatment showed complete disappearance of
      the lesion in 2 patients, more than 50% improvement in 5, less than 50%
      improvement in 5, and no change of lesion in 4. CONCLUSION: Edematous-type EBTB
      was the most common type of EBTB presenting as RMLS, and it usually occurred in
      elderly patients. Culturing for mycobacterium and histologic examination by
      bronchoscopy are necessary for proper diagnosis in these patients.

PMID- 18729305
TI  - Second line palliative endobronchial radiotherapy with HDR Ir 192 in recurrent
      lung carcinoma.
AB  - PURPOSE: To observe the efficiency of reirradiation with high dose rate
      intraluminal brachytherapy in symptomatic palliation of recurrent endobronchial
      tumors. MATERIALS AND METHODS: Between January 1994 and June 1998, 21 patients
      diagnosed with recurrent endobronchial tumors following external beam
      radiotherapy were treated palliatively with high dose rate intraluminal
      irradiation at Hacettepe University Oncology Institute. A single fraction of 10
      Gy was prescribed to the specified area in 9 patients and 15 Gy to 12. RESULTS:
      Endobronchial treatment improved the performance and reduced symptomatology in 17
      (81%) patients. Ten dyspneic patients (10/14, 71%) recovered clinically with an
      accompanying radiological downstaging. The median symptomatic palliation was 45
      days (range, 0-9 months), and the overall median survival was 5.5 months (range,
      4-12 months). The palliative intrabronchial brachytherapy was well tolerated,
      with the exception of in one patient with a fatal hemorrhage, and another with
      medically salvaged bronchospasm and intrabronchial edema. CONCLUSION: Recurrent
      patients with a history of previous thoracic external beam irradiation can be
      effectively palliated with high dose rate endobronchial reirradiation if the
      symptoms are directly related to the endobronchial tumor.

PMID- 18729306
TI  - N-terminal pro B-type natriuretic peptide and the evaluation of cardiac
      dysfunction and severity of disease in cirrhotic patients.
AB  - PURPOSE: Cardiac dysfunction and hyperdynamic systemic circulation may be present
      in patients with cirrhosis. The purpose of this study was to identify relations
      between plasma levels of N-terminal-proBNP (NT-proBNP), reflecting early
      ventricular dysfunction, and the severity of liver disease and cardiac
      dysfunction in cirrhotic patients. MATERIALS AND METHODS: Sixty-three cirrhotic
      patients and 15 controls (group 1) were enrolled in this study. Plasma levels of
      NT-proBNP were determined in echocardiographically examined patients, which were
      allocated to 1 of 3 groups according to Child-Pugh classification or into 2
      groups, i.e., a compensated group without ascites (group 2) and decompensated
      group with ascites (group 3). RESULTS: Plasma NT-proBNP levels were significantly
      higher in cirrhotic patients (groups 2 and 3) than in age-matched controls (155.9
      and 198.3 vs. 40.3 pg/mL, respectively, p < 0.05). NT-proBNP levels were
      significantly increased in Child class C patients than in classes B and A (250.0
      vs. 168.6 and 119.6 pg/mL, respectively, p < 0.05). Left atrial dimension, wall
      thickness of left ventricle, and EF or E/E' were significantly increased, and EDT
      was prolonged in cirrhotic patients than in controls. Increased LVMI and
      decreased E/A ratio were noted in the group of patients with ascites as compared
      with the other groups. CONCLUSION: Plasma NT-proBNP levels were high in cirrhotic
      patients and are likely to be related to the severity of disease. Advanced
      cirrhosis is associated with advanced cardiac dysfunction, and NT-proBNP levels
      has predictive value for concomitant cardiac dysfunction and cirrhosis
      progression.

PMID- 18729307
TI  - Early experiences of robotic-assisted laparoscopic liver resection.
AB  - PURPOSE: The surgical robotic system is superior to traditional laparoscopy in
      regards to 3-dimensional images and better instrumentations. Robotic surgery for
      hepatic resection has not yet been extensively reported. PATIENTS AND METHODS:
      Between March and May 2007, we performed 3 robot-assisted left lateral
      sectionectomies of the liver. Case 1 had a hepatocellular carcinoma (HCC), case 2
      had colon cancer with liver metastasis, and case 3 had intrahepatic duct stones.
      RESULTS: All patients had successful operation and recovered without
      complications. Shorter length of hospital stays, earlier start of oral feeding
      and less amount of ascites were found. However, case 1 had recurrent HCC at 3
      months after operation. CONCLUSION: Robotic-assisted liver surgery is still a new
      field in its developing stage. In patients with small malignant tumors and benign
      liver diseases, robotic-assisted laparoscopic resection is feasible and safe.
      Through experience, the use of robotics is expected to increase in the treatment
      of benign diseases and malignant neoplasms. However, careful patient selection is
      important and long-term outcomes need to be evaluated.

PMID- 18729308
TI  - A multi-institutional study on histopathological characteristics of surgically
      treated renal tumors: the importance of tumor size.
AB  - PURPOSE: The incidence of accidentally detected small renal tumors is increasing
      throughout the world. In this multi-institutional study performed in Korea,
      histopathological characteristics of contemporarily surgically removed renal
      tumors were reviewed with emphasis on tumor size. MATERIALS AND METHODS: Between
      January 1995 and May 2005, 1,702 patients with a mean age of 55 years underwent
      surgical treatment at 14 training hospitals in Korea for radiologically suspected
      malignant renal tumors. Clinicopathological factors and patient survival were
      analyzed. RESULTS: Of the 1,702 tumors, 91.7% were malignant and 8.3% were
      benign. The percentage of benign tumors was significantly greater among those <
      or = 4 cm (13.2%) than those > 4 cm (4.5%) (p < 0.001). Among renal cell
      carcinoma patients, the percentage of tumors classed as stage > or = T3 was
      significantly less among tumors < or = 4 cm (5.2%) than those > 4 cm (26.8%) (p <
      0.001). The percentage of tumors classed as Fuhrman's nuclear grades > or = 3 was
      also significantly less among tumors < or = 4 cm (27.3%) than tumors > 4 cm
      (50.9%) (p < 0.001). The 5-year cancer-specific survival rate was 82.7%, and T
      stage (p < 0.001), N stage (p < 0.001), M stage (p = 0.025), and Fuhrman's
      nuclear (p < 0.001) grade were the only independent predictors of cancer-specific
      survival. CONCLUSION: In renal tumors, small tumor size is prognostic for
      favorable postsurgical histopathologies such as benign tumors, low T stages, and
      low Fuhrman's nuclear grades. Our observations are expected to facilitate
      urologists to adopt function-preserving approach in the planning of surgery for
      small renal tumors with favorable predicted outcomes.

PMID- 18729309
TI  - Effectiveness of different cleaning agents against the colonization of Candida
      spp and the in vitro detection of the adherence of these yeast cells to denture
      acrylic surfaces.
AB  - PURPOSE: The aim of this study is to examine the effect Klorhex and Fittydent,
      which are used as cleaning agents on the adhesion of Candida on the surfaces of
      acrylic denture and palatal mucosa. In addition, ability of yeasts to adhere to
      acrylic strips was evaluated after applying these agents in vitro. MATERIALS AND
      METHODS: Each group of 15 patients cleaned their dentures with either Klorhex or
      with Fittydent. The control group cleaned their dentures with water. RESULTS: It
      was found that 62.2% of the patients had colonies of Candida species on their
      palatal mucosa which was reduced to 51.1% after using these cleaning agents. The
      colonization rate with Candida spp on their dentures was reduces from 82.2% to
      68.8% using these cleaning agents. The mean adhesion value of the Candida strains
      isolated from the acrylic strips were found to be 75 cell/strip prior to applying
      the Klorhex and Fittydent and 37.5 cell/strip and 15 cell/strip after applying
      these agents, respectively. CONCLUSION: These results showed that Klorhex and
      Fittydent have a certain preventive effect on the colonization rate of Candida
      spp on the surface of these dentures, the palatal mucosa, as well as on the
      acrylic strips in vitro.

PMID- 18729311
TI  - Delayed epithelial ingrowth caused by viral conjunctivitis after LASIK.
AB  - To report a patient who presented with epithelial ingrowth caused by viral
      keratoconjunctivitis 3 months after LASIK surgery. A 41-year-old man presented
      with decreased visual acuity in the right eye, which had developed about 3 weeks
      before. He had undergone LASIK surgery 3 months prior without complications. Two
      months after the surgery, he was treated for viral conjunctivitis. During the
      treatment period, filamentary keratitis developed, and a therapeutic bandage
      contact lens was applied for 2 weeks. Upon presentation, examination revealed a
      corrected visual acuity of 20/100 and irregular epithelial sheets under the
      edematous flap. The flap was lifted, and the in-grown epithelium was removed. The
      flap was repositioned with double continuous 10-0 nylon sutures. Post
      operatively, the patient developed a mild diffuse lamellar keratitis that
      resolved rapidly with topical corticosteroid treatment. At 2 months, the
      corrected visual acuity was 20/20 without interface opacities. As the patient
      showed no complications prior to viral conjunctivitis, we suspect that the viral
      infection caused edema of the corneal flap, which caused epithelial ingrowth
      under the flap. Patients who have viral conjunctivitis after LASIK surgery should
      be examined carefully and managed with consideration of flap complications.

PMID- 18729310
TI  - Multiple endocrine neoplasia type 1 with multiple leiomyomas linked to a novel
      mutation in the MEN1 gene.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited
      syndrome. MEN1 is characterized by the presence of functioning and nonfunctioning
      tumors or hyperplasia of the pituitary gland, parathyroid glands, and pancreatic
      islet cells. In addition, MEN1 carriers can have adrenal or thyroid tumors and
      non-endocrine tumors, such as lipomas, angiofibromas, and leiomyomas. Although
      leiomyoma is not a major component of MEN1, it is thought to occur more
      frequently than expected. However, there has been no report of a case of MEN1
      with leiomyoma in Korea so far. This report describes a patient with multiple
      leiomyomas in MEN1. A 50-year-old woman was referred for further evaluation of
      elevated calcium levels and osteoporosis. Biochemical abnormalities included
      hypercalcemia with elevated parathyroid hormone. There was hyperprolactinemia
      with pituitary microadenoma in sella MRI. An abdominal MRI demonstrated adrenal
      nodules and leiomyomas in the bladder and uterus. Endoscopic ultrasonography
      demonstrated esophageal leiomyoma and pancreatic islet cell tumor. A subtotal
      parathyroidectomy with thymectomy was performed. Sequencing of the MEN1 gene in
      this patient revealed a novel missense mutation (D350V, exon 7). This is the
      first case of MEN1 accompanied with multiple leiomyomas, parathyroid adenoma,
      pituitary adenoma, pancreatic tumor, and adrenal tumor.

PMID- 18729312
TI  - Symptomatic posterior mediastinal angioleiomyoma.
AB  - We report a case of a symptomatic angioleiomyoma in the left posterior
      mediastinum. A 66-year-old woman presented with left back and flank pain for 6
      months. Chest computed tomography (CT) and magnetic resonance imaging (MRI)
      revealed a well-circumscribed 4.3 cm round mass. The mass was initially diagnosed
      as nerve sheath tumor, because of her symptoms and its close location to the
      sympathetic trunk and intercostal nerve. It was uneventfully removed through
      video-assisted thoracoscopic surgery. The pathology revealed an angioleiomyoma.

PMID- 18729313
TI  - Iatrogenic gastric dilatation: a rare and transient cause of hepatic-portal
      venous gas.
AB  - Gas in the portal veins is rare and in most cases is associated with serious
      diseases and poor clinical outcome. A case of gas in the hepatic-portal veins
      with gastric dilatation, as shown by CT-scanning for abdominal trauma, is
      reported. The condition was clinically benign and resolved spontaneously. An
      abdominal CT scan documented the findings.

PMID- 18729314
TI  - A spindle cell predominant pancreatic solid-pseudopapillary tumor.
AB  - A hitherto unrecognized variant of solid-pseudopapillary tumor (SPT) of the
      pancreas is reported. The tumor presented in the pancreatic tail of a 44-year-old
      female patient. It was a well-defined, solid nodule measuring 25 mm in diameter,
      with homogenous tan gray cut surface. Histologically, the neoplasm was mostly
      composed of sheets of spindle cells. No cellular atypia and mitosis was
      identified. The periphery of the tumor showed typical feature of SPT.
      Immunohistochemically, the tumor cells were positive for vimentin, CD10, CD56,
      beta-catenin, and alpha1-antichymotrypsin, but negative for cytokeratin,
      chromogranin, synaptophysin and S-100 protein. Ultrastructurally, the tumor
      showed a few acinar spaces with microvilli between tumor cells. This case is
      peculiar in that the tumor did not show gross cystic change and predominantly
      consists of spindle shaped tumor cells, so may cause difficult diagnostic
      problem.

PMID- 18729315
TI  - Pulmonary edema after catastrophic carbon dioxide embolism during laparoscopic
      ovarian cystectomy.
AB  - Laparoscopy is a surgical procedure used both for diagnosis and for various
      treatments. A rare but sometimes fatal complication of laparoscopy is pulmonary
      embolism with CO2 resulting in pulmonary edema. During laparoscopic gynecological
      surgery in a 29-year-old woman who had previously undergone lower abdominal
      surgery, the end-tidal CO2 suddenly increased from 40 mmHg to 85 mmHg and then
      decreased to 13 mmHg with hemodynamic deterioration. These events are
      characteristic of a CO2 embolism. When this occurred, CO2 insufflation was
      immediately stopped and the patient was resuscitated. The patient's condition
      gradually improved with aggressive treatment, but the clinical course was
      complicated by bilateral pulmonary edema. This case of pulmonary edema was soon
      resolved with supportive management. The formation of a CO2 embolism during
      laparoscopy must be suspected whenever there is a sudden change in the end-tidal
      CO2. In addition, the possibility of pulmonary edema should be considered when a
      CO2 embolism occurs.

PMID- 18729316
TI  - Needle knife-assisted endoscopic polypectomy for a large inflammatory fibroid
      colon polyp by making its stalk into an omega shape using an endoloop.
AB  - Colonic inflammatory fibroid polyp (IFP) is an uncommon benign polypoid lesion,
      which is composed of fibroblasts, numerous small vessels and edematous connective
      tissue with marked eosinophilic inflammatory cell infiltration. This condition is
      frequently detected in the stomach and small intestine, but uncommon in the
      colon. Although IFP is a benign lesion, surgical resections are performed in most
      colonic cases because the polyps are usually too large to resect endoscopically.
      Only three patients underwent endoscopic polypectomy in our literature reviews.
      Here, we present a case of IFP in the descending colon successful endoscopically
      resected using a novel technique of trapping its stalk with an endoloop, forming
      the stalk into an omega shape, and then dissecting the stalk with a needle knife.

PMID- 18729318
TI  - Critical assessment of QSAR models of environmental toxicity against Tetrahymena
      pyriformis: focusing on applicability domain and overfitting by variable
      selection.
AB  - The estimation of the accuracy of predictions is a critical problem in QSAR
      modeling. The "distance to model" can be defined as a metric that defines the
      similarity between the training set molecules and the test set compound for the
      given property in the context of a specific model. It could be expressed in many
      different ways, e.g., using Tanimoto coefficient, leverage, correlation in space
      of models, etc. In this paper we have used mixtures of Gaussian distributions as
      well as statistical tests to evaluate six types of distances to models with
      respect to their ability to discriminate compounds with small and large
      prediction errors. The analysis was performed for twelve QSAR models of aqueous
      toxicity against T. pyriformis obtained with different machine-learning methods
      and various types of descriptors. The distances to model based on standard
      deviation of predicted toxicity calculated from the ensemble of models afforded
      the best results. This distance also successfully discriminated molecules with
      low and large prediction errors for a mechanism-based model developed using log P
      and the Maximum Acceptor Superdelocalizability descriptors. Thus, the distance to
      model metric could also be used to augment mechanistic QSAR models by estimating
      their prediction errors. Moreover, the accuracy of prediction is mainly
      determined by the training set data distribution in the chemistry and activity
      spaces but not by QSAR approaches used to develop the models. We have shown that
      incorrect validation of a model may result in the wrong estimation of its
      performance and suggested how this problem could be circumvented. The toxicity of
      3182 and 48774 molecules from the EPA High Production Volume (HPV) Challenge
      Program and EINECS (European chemical Substances Information System),
      respectively, was predicted, and the accuracy of prediction was estimated. The
      developed models are available online at http://www.qspr.org site.

PMID- 18729319
TI  - One-electron reduction of superoxide radical-anions by 3-alkylpolyhydroxyflavones
      in micelles. Effect of antioxidant alkyl chain length on micellar structure and
      reactivity.
AB  - In micellar solutions, one-electron reduction of *O2(-) radical-anions by 3
      alkylpolyhydroxyflavones (FnH) with alkyl chains of n = 1, 4, 6, 10 carbons
      produces phenoxyl radicals ( (*Fn) identical to those obtained by one-electron
      oxidation by *Br2(-) radical-anions or by repair of tryptophan radicals. In
      cetyltrimethylammonium bromide (CTAB), F1H localizes in the Stern layer, and
      alkyl chains of other FnH solubilize in the hydrophobic interior, interacting
      with cetyl tails. This interaction produces more compact micelles with lower
      intramicellar fluidity, as suggested by the increase in the pseudo-first-order
      rate constant of *Fn formation ( k 1) from approximately 390 s (-1) for n = 1 to
      610 s (-1) for n = 10, leading to an intramicellar bimolecular rate constant of 1
      x 10 (5) M (-1) s (-1). Additionally, *F1 and *F4 decay by intermicellar
      bimolecular reaction (2 k = 20 and 2 x 10 (5) M (-1) s (-1), respectively)
      whereas other *Fn radicals are stable over seconds due to increased localization
      with regards to the Stern layer. In contrast, the thick uncharged hydrophilic
      palisade layer and the compact hydrophobic core of Triton X100 micelles are
      responsible for a much higher microviscosity resulting in a decrease in k 1 from
      approximately 15.6 s (-1) for n = 1 to 9.6 s (-1) for n = 10.

PMID- 18729320
TI  - Synthesis of platinum nanowheels using a bicellar template.
AB  - Disk-like surfactant bicelles provide a unique meso-structured reaction
      environment for templating the wet-chemical reduction of platinum(II) salt by
      ascorbic acid to produce platinum nanowheels. The Pt wheels are 496 +/-55 nm in
      diameter and possess thickened centers and radial dendritic nanosheets (about 2
      nm in thickness) culminating in flared dendritic rims. The structural features of
      the platinum wheels arise from confined growth of platinum within the bilayer
      that is also limited at edges of the bicelles. The size of CTAB/FC7 bicelles is
      observed to evolve with the addition of Pt(II) complex and ascorbic acid.
      Synthetic control is demonstrated by varying the reaction parameters including
      metal salt concentration, temperature, and total surfactant concentration. This
      study opens up opportunities for the use of other inhomogeneous soft templates
      for synthesizing metals, metal alloys, and possibly semiconductors with complex
      nanostructures.

PMID- 18729322
TI  - Synthesis of fused piperidinones through a radical-ionic cascade.
AB  - Azabicyclo[4.3.0]nonanes were assembled, from chiral allylsilanes possessing an
      oxime moiety, using a stereocontrolled formal [2 + 2 + 2] radical-ionic process.
      The cascade involves the addition of an alpha-iodoester to the less substituted
      end of the enoxime which is then followed by a 5-exo-trig cyclization onto the
      aldoxime function, producing an alkoxyaminyl radical species which finally
      lactamizes to afford the titled piperidinone. High levels of stereoinduction were
      observed, demonstrating the ability of a silicon group located at the allylic
      position to efficiently control the stereochemistry of the two newly created
      stereogenic centers. When the radical cascade was extended to ketoximes, the
      resulting sterically hindered alkoxyaminyl radical did not react further with the
      initiator Et3B to produce the expected nucleophilic amidoborane complex. In sharp
      contrast, this long-lived radical recombined with the initial alpha-stabilized
      ester radical to produce a cyclopentane incorporating two ester fragments.

PMID- 18729321
TI  - DNA interaction with antitumor polyamine analogues: a comparison with biogenic
      polyamines.
AB  - Biogenic polyamines, putrescine, spermidine, and spermine, are ubiquitous
      cellular cations and exert multiple biological functions. Polyamine analogues
      mimic biogenic polyamines at macromolecular level but are unable to substitute
      for natural polyamines and maintain cell proliferation, indicating biomedical
      applications. The mechanistic differences in DNA binding mode between natural and
      synthetic polyamines have not been explored. The aim of this study was to examine
      the interaction of calf thymus DNA with three polyamine analogues, 1,11-diamino
      4,8-diazaundecane (333), 3,7,11,15-tetrazaheptadecane x 4 HCl (BE-333), and
      3,7,11,15,19-pentazahenicosane x 5 HCl (BE-3333), using FTIR, UV-visible, and CD
      spectroscopy. Polyamine analogues bind with guanine and backbone PO2 group as
      major targets in DNA, whereas biogenic polyamines bind to major and minor grooves
      as well as to phosphate groups. Weaker interaction with DNA was observed for
      analogues with respect to biogenic polyamines, with K(333) = 1.90 (+/-0.5) x
      10(4) M(-1), K(BE-333) = 6.4 (+/-1.7) x 10(4) M(-1), K(BE-3333) = 4.7 (+/-1.4) x
      10(4) M(-1) compared to K(Spm) = 2.3 (+/-1.1) x 10(5) M(-1), K(Spd) = 1.4 (+/
      0.6) x 10(5) M(-1), and K(Put) = 1.02 (+/-0.5) x 10(5) M(-1). A partial B- to A
      DNA transition was also provoked by analogues. These data suggest distinct
      differences in the binding of natural and synthetic polyamines with DNA.

PMID- 18729323
TI  - A Novel synthesis of 2-functionalized benzofurans by palladium-catalyzed
      cycloisomerization of 2-(1-hydroxyprop-2-ynyl)phenols followed by acid-catalyzed
      allylic isomerization or allylic nucleophilic substitution.
AB  - A novel two-step synthesis of 2-hydroxymethylbenzofurans 3 and 2
      alkoxymethylbenzofurans 4-6, based on palladium-catalyzed cycloisomerization of 2
      (1-hydroxyprop-2-ynyl)phenols 1 under basic conditions to give 2-methylene-2,3
      dihydrobenzofuran-3-ols 2, followed by acid-catalyzed isomerization or allylic
      nucleophilic substitution with alcohols as nucleophiles, is reported.
      Cycloisomerization reactions leading to 2 (80-98% yields) were carried out at 40
      degrees C in MeOH as the solvent, in the presence of a base and catalytic amounts
      of PdX2 + 2KX (X = Cl, I). Isomerization reactions of 2 readily occurred at 25-60
      degrees C in DME as the solvent, with H2SO4 as the proton source, to give 2
      hydroxymethylbenzofurans 3 in 65-90% yields. In a similar manner, allylic
      nucleophilic substitution reactions of 2 with ROH as nucleophiles [carried out at
      25-40 degrees C in ROH (R = Me) or ROH-DME mixtures (R = Bu, Bn) in the presence
      of H2SO4] afforded 2-alkoxymethylbenzofurans 4, 5, and 6 (R = Me, Bu, and Bn,
      respectively), in 65-98% yields.

PMID- 18729324
TI  - Hetero-double-helix formation by an ethynylhelicene oligomer possessing
      perfluorooctyl side chains.
AB  - Monomeric to pentameric (P)-ethynylhelicene oligomers possessing perfluorooctyl
      side chains were synthesized. The circular dichroism (CD) and vapor pressure
      osomometry (VPO) studies indicated the formation of a helix-dimer for the (P)
      pentamer, for example, in trifluoromethylbenzene at 5 degrees C at concentrations
      above 2 x 10(-6) M. Compared with a (P)-pentamer possessing decyloxycarbonyl side
      chains, the perfluorooctyl (P)-pentamer exhibited lower solubilities in organic
      solvents, formed a thermodynamically more stable helix-dimer, and exhibited a
      mirror image CD spectrum. The perfluorooctyl (P)-pentamer formed a hetero-helix
      dimer with a decyloxycarbonyl (M)-pentamer but not with a (P)-pentamer. It
      indicated higher stability of the hetero-helix dimer over the homo-helix dimers.

PMID- 18729325
TI  - The muddle of models: what you don't know can hurt you.
AB  - Prior to clinical trials, animal models remain the primary tools by which the
      pharmaceutical industry demonstrates the efficacy and safety of candidate
      therapeutic agents. Despite this reliance, much remains unknown about the models
      that we use and the factors that affect how they perform. This ignorance can lead
      to inappropriate assumptions, questionable procedures, and incorrect conclusions
      from data generated in these models. This perspective provides a narrative of
      several such instances and provides recommendations as to how we might address
      our knowledge gap by better characterization of our models, better understanding
      of our practices, and better control of our studies.

PMID- 18729326
TI  - Quantification of sulforaphane mercapturic acid pathway conjugates in human urine
      by high-performance liquid chromatography and isotope-dilution tandem mass
      spectrometry.
AB  - We report validation of the first high-pressure liquid chromatography isotope
      dilution mass spectrometry method to measure sulforaphane (SFN) and its
      glutathione-derived conjugates in human urine. As epidemiological evidence
      continues to mount that the consumption of a diet rich in cruciferous vegetables
      may reduce the risk of certain cancers, the development of analytical
      methodologies to accurately measure isothiocyanates (ITCs) and their subsequent
      metabolic products becomes paramount. SFN, the principal ITC produced by
      broccoli, is an effective chemopreventive agent with multiple modes of action.
      SFN and SFN conjugates have often been measured collectively utilizing a
      cyclocondensation assay with 1,2-benzenedithiol. More recently, some of the major
      SFN conjugates have been determined using mass spectrometry. Here, triple
      quadrupole mass spectrometry has been coupled with the use of stable isotope
      labeled internal standards of D8-SFN and all four D8-SFN mercapturic acid pathway
      conjugates to provide an accurate, precise, sensitive, and specific method for
      analysis of these compounds. Using urine samples collected during an earlier
      intervention with broccoli sprouts, the concentrations of SFN, SFN-cysteine, and
      the mercapturic acid SFN- N-acetylcysteine were sufficiently high such that as
      little as 50 nL of urine was required for analysis. Although each study
      participant received an equivalent dose of broccoli sprout preparation, the
      interindividual conversion of the precursor glucosinolate to SFN varied over 100
      fold. These 98 urines provided an ideal sample set for examining the robustness
      of the assay. The mean urinary concentrations +/- standard deviations in
      overnight voids following ingestion of the first dose were 4.7 +/- 5.1, 0.03 +/-
      0.05, 0.06 +/- 0.06, 18 +/- 15, and 42 +/- 23 nmol/mg creatinine for SFN, SFN
      glutathione, SFN-cysteine-glycine, SFN-cysteine, and SFN- N-acetylcysteine,
      respectively. This method determines SFN and all four SFN glutathione-derived
      metabolites with minimal sample preparation and will be extremely useful in
      understanding the role of SFN-rich foods in preventing cancer and other chronic
      diseases.

PMID- 18729327
TI  - Modification of serine 360 by a reactive intermediate of 17-alpha
      ethynylestradiol results in mechanism-based inactivation of cytochrome P450s 2B1
      and 2B6.
AB  - 17-alpha-Ethynylestradiol (17EE) is a mechanism-based inactivator of P450 2B1 and
      P450 2B6 in the reconstituted monooxygenase system. The loss in enzymatic
      activity was due to the binding of a reactive intermediate of 17EE to the
      apoprotein. P450 2B1 and P450 2B6 were inactivated by 17EE and digested with
      trypsin. The peptides obtained following digestion with trypsin of 17EE
      inactivated P450 2B1 and P450 2B6 were separated by liquid chromatography and
      analyzed by ESI-MS. Adducted peptides exhibiting an increase in mass consistent
      with the addition of the mass of the reactive intermediate of 17EE were
      identified for each enzyme. Analysis of these modified peptides by ESI-MS/MS and
      precursor ion scanning facilitated the identification of the Ser360 in both
      enzymes as a site that had been adducted by a reactive intermediate of 17EE. A
      P450 2B1 mutant where Ser360 was replaced by alanine was constructed, expressed,
      and purified. Activity and inactivation studies indicated that mutation of the
      Ser360 residue to alanine did not prevent inactivation of the mutant enzyme by
      17EE. These observations suggest that Ser360 is not critical for the catalytic
      function of these P450s. Spectral binding studies of the 17EE-inactivated P450
      2B1 and P450 2B6 indicated that modification of the enzymes by the reactive
      intermediate of 17EE resulted in an enzyme that was no longer capable of binding
      substrates. These results suggest that the inactivation by 17EE may be due to
      modification of an amino acid residue in the substrate access channel near the
      point of entry into the active site.

PMID- 18729328
TI  - Prospective type 1 and type 2 disulfides of Keap1 protein.
AB  - Experiments were carried out to detect cysteine residues on human Keap1 protein
      that may be sensors of oxidative stress that gives rise to changes in the
      GSH/GSSG redox couple. Human Keap1 protein, at a final concentration of 6 microM,
      was incubated for two hours in aqueous buffer containing 0.010 M GSH, pH 8, in an
      argon atmosphere. Subsequently, excess iodoacetamide and trypsin were added to
      generate a peptide map effected by LCMS analysis. Peptides containing all 27
      carboxamidomethylated cysteines were identified. Replacement of GSH by 0.010 M
      GSSG yielded a map in which 13 of the original carboxamidomethylated peptides
      were unperturbed, while other caboxamidomethylated cysteine-containing peptides
      were undetected, and a number of new cysteine-containing peptide peaks were
      observed. By mass analysis, and in some cases, by isolation, reduction,
      carboxamidomethylation, and reanalysis, these were identified as S
      glutathionylated (Type 1) or Cys-Cys (Type 2) disulfides. Such peptides derived
      from the N-terminal, dimerization, central linker, Kelch repeat and C-terminal
      domains of Keap1. Experiments were carried out in which Keap1 was incubated
      similarly but in the presence of various GSH/GSSG ratios between 100 and 1 ([GSH
      + GSSG] = 0.010 M), with subsequent caraboxamidomethylation and trypsinolysis to
      determine differences in sensitivities of the different cysteines to the type 1
      and type 2 modifications. Cysteines most sensitive to S-glutathionylation include
      Cys77, Cys297, Cys319, Cys368, and Cys434, while cysteine disulfides most readily
      formed are Cys23-Cys38 and Cys257-Cys297. The most reducing conditions at which
      these modifications are at GSH/GSSG = 10, which computes to an oxidation
      potential of E h = -268.5 mV, a physiologically relevant value. Under somewhat
      more oxidizing, but still physiologically relevant, conditions, GSH/GSSG = 1 ( E
      h = -231.1 mV), a Cys319-Cys319 disulfide is detected far from the dimerization
      domain of the Keap1 homodimer. The potential impact on protein structure of the
      glutathionylation of Cys434 and Cys368, the two modified residues in the Kelch
      repeat domain, was analyzed by docking and energy minimizations of glutathione
      residues attached to the Kelch repeat domain, whose coordinates are known. The
      energy minimizations indicated marked alterations in structure with a substantial
      constriction of Neh2 binding domain of the Keap1 Kelch repeat domain. This
      alteration appears to be enforced by an extended hydrogen-bonding network between
      residues on the glutathione moiety attached to Cys434 and amino acid side chains
      that have been shown to be essential for repression of Nrf2 by Keap1. The
      modifications of Keap1 detected in the present study are discussed in the context
      of previous work of others who have examined the sensitivity of cysteines on
      Keap1 to electrophile assault.

PMID- 18729329
TI  - UVB-exposed chlorinated bisphenol A generates phosphorylated histone H2AX in
      human skin cells.
AB  - Bisphenol A (BPA) and chlorinated bisphenol A (ClBPAs) were detected in
      wastewater from waste paper recycling plants. Previously, we showed that exposure
      to UV augmented the toxicity of ClBPAs [Mutou (2006) Environ. Toxicol. Pharmacol.
      21, 283- 289 and Mutou (2008) Toxicol. in Vitro 22, 864- 872]. BPA and ClBPAs are
      exposed to sunlight in the environment; however, research concerning the change
      of toxicity during their photodegradation is scarce, especially for ClBPAs. In
      this study using human keratinocytes and skin fibroblasts, we found that 3,3'
      dichlorobisphenol A (3,3'-diClBPA) exposed to UVB induces phosphorylation of
      histone H2AX, the event considered to be a marker of formation of DNA double
      strand breaks. The cells treated with the UVB-exposed 3,3'-diClBPA formed clear
      foci of phosphorylated histone H2AX in the nucleus. Unchlorinated BPA caused no
      phosphorylation of histone H2AX even when exposed to high doses of UVB
      (approximately 200 J/cm(2)). HPLC analysis clarified that several compounds with
      increased hydrophilicity were produced from 3,3'-diClBPA by UVB irradiation, not
      from BPA, suggesting the chlorinated chemical structure to be important for the
      degradation and generation of products related to the phosphorylation of histone
      H2AX. In separated peaks of 3,3'-diClBPA exposed to UVB, peak fluctuation of 3
      hydroxybisphenol A (3-OHBPA) was consistent with the UVB dose-dependent
      appearance of phosphorylated histone H2AX. We suspected that some oxidized BPA
      involving 3-OHBPA produced by UVB irradiation contributed to the phosphorylation.
      Considering that the phosphorylation of histone H2AX is required for maintaining
      the genome's stability and the repair of DNA, attention to photoproducts from
      chlorinated compounds is important for the risk evaluation of chemicals.

PMID- 18729331
TI  - Aminoacetone, a putative endogenous source of methylglyoxal, causes oxidative
      stress and death to insulin-producing RINm5f cells.
AB  - Aminoacetone (AA), triose phosphates, and acetone are putative endogenous sources
      of potentially cytotoxic and genotoxic methylglyoxal (MG), which has been
      reported to be augmented in the plasma of diabetic patients. In these patients,
      accumulation of MG derived from aminoacetone, a threonine and glycine catabolite,
      is inferred from the observed concomitant endothelial overexpression of
      circulating semicarbazide-sensitive amine oxidases. These copper-dependent
      enzymes catalyze the oxidation of primary amines, such as AA and methylamine, by
      molecular oxygen, to the corresponding aldehydes, NH4(+) ion and H2O2. We
      recently reported that AA aerobic oxidation to MG also takes place immediately
      upon addition of catalytic amounts of copper and iron ions. Taking into account
      that (i) MG and H2O2 are reportedly cytotoxic to insulin-producing cell lineages
      such as RINm5f and that (ii) the metal-catalyzed oxidation of AA is propagated by
      O2(*-) radical anion, we decided to investigate the possible pro-oxidant action
      of AA on these cells taken here as a reliable model system for pancreatic beta
      cells. Indeed, we show that AA (0.10-5.0 mM) administration to RINm5f cultures
      induces cell death. Ferrous (50-300 microM) and Fe(3+) ion (100 microM) addition
      to the cell cultures had no effect, whereas Cu(2+) (5.0-100 microM) significantly
      increased cell death. Supplementation of the AA- and Cu(2+)-containing culture
      medium with antioxidants, such as catalase (5.0 microM), superoxide dismutase
      (SOD, 50 U/mL), and N-acetylcysteine (NAC, 5.0 mM) led to partial protection.
      mRNA expression of MnSOD, CuZnSOD, glutathione peroxidase, and glutathione
      reductase, but not of catalase, is higher in cells treated with AA (0.50-1.0 mM)
      plus Cu(2+) ions (10-50 microM) relative to control cultures. This may imply
      higher activity of antioxidant enzymes in RINm5f AA-treated cells. In addition,
      we have found that AA (0.50-1.0 mM) plus Cu(2+) (100 microM) (i) increase RINm5f
      cytosolic calcium; (ii) promote DNA fragmentation; and (iii) increase the pro
      apoptotic (Bax)/antiapoptotic (Bcl-2) ratio at the level of mRNA expression. In
      conclusion, although both normal and pathological concentrations of AA are
      probably much lower than those used here, it is tempting to propose that excess
      AA in diabetic patients may drive oxidative damage and eventually the death of
      pancreatic beta-cells.

PMID- 18729332
TI  - Demonstration of the metabolic pathway responsible for nevirapine-induced skin
      rash.
AB  - The reverse transcriptase inhibitor, nevirapine (NVP), causes skin rashes and
      hepatotoxicity. We used a rat model to determine if the rash is caused by the
      parent drug or a reactive metabolite. By manipulation of metabolic pathways and
      testing analogues, we eliminated all but one pathway, 12-hydroxylation, which
      involves the oxidation of an exocyclic methyl group, as being responsible for the
      rash. Treatment with 12-OH-NVP caused a rash, and an analogue in which the methyl
      hydrogens were replaced by deuterium to inhibit the 12-OH pathway did not cause a
      rash; however, quite unexpectedly, blood levels of the deuterated analogue were
      very low. This is due to partitioning of the benzylic free radial intermediate
      between oxygen rebound to form 12-OH-NVP and loss of another hydrogen atom to
      form a reactive quinone methide, which inactivates P450. Cotreatment with the
      P450 inhibitor, 1-aminobenzotriazole, led to comparable levels of NVP and the
      deuterated analogue, and the deuterated analogue still caused a lower rash
      incidence. These data clearly point to the 12-hydroxy pathway being responsible
      for NVP skin rash. We propose that the hepatotoxicity of NVP in humans is due to
      the quinone methide formed by P450 in the liver, while the skin rash may be due
      to the quinone methide formed in the skin by sulfation of 12-OH metabolite
      followed by loss of sulfate. This is the first example in which a valid animal
      model of an idiosyncratic drug reaction was used to determine the metabolic
      pathway responsible for the reaction.

PMID- 18729333
TI  - Lyotropic liquid-crystalline mesophases of [Zn(H2O)6](NO3)2-C12EO10-CTAB-H2O and
      [Zn(H2O)6](NO3)2-C12EO10-SDS-H2O systems.
AB  - The mixture of two surfactants (C12EO10-CTAB and C12EO10-SDS) forms lyotropic
      liquid-crystalline (LLC) mesophases with [Zn(H2O)6](NO3)2 in the presence of a
      minimum concentration of 1.75 H2O per C12EO10. The metal ion/C12EO10 mole ratio
      can be increased up to 8.0, which is a record high metal ion density in an LLC
      mesophase. The metal ion concentration can be increased in the medium by
      increasing the CTAB/C12EO10 or SDS/C12EO10 mole ratio at the expense of the
      stability of the LLC mesophase. The structure and some thermal properties of the
      new mesophase have been investigated using XRD, POM, FTIR, and Raman techniques.

PMID- 18729334
TI  - Size-dependent surface reactions of Ag nanoparticles supported on highly oriented
      pyrolytic graphite.
AB  - Various sizes of Ag particles were grown on highly oriented pyrolytic graphite
      (HOPG) surfaces, which had previously been modified with nanopits to act as
      anchoring sites. Surface reactions of O2, CHCl3, and CCl4 on the Ag particles and
      bulk Ag(111) surfaces were studied by X-ray photoelectron spectroscopy (XPS), and
      it has been shown that size dependence of O2 and CHCl3 reactions on Ag differs
      from that of CCl4. Weak reactions of O2 and CHCl3 were observed on the bulk
      Ag(111) surfaces, while strong reactions occur on Ag particles with medium Ag
      coverage, suggesting that the reactions are controlled by the number of surface
      defect sites. On the contrary, the dissociation of CCl4 is mainly determined by
      the exposed Ag facet area, mainly Ag(111) facet, and strong dissociation reaction
      happens on the bulk Ag(111) surface. The results suggest that the size effects,
      which are often discussed in heterogeneous catalysis, are strongly dependent on
      the reaction mechanism.

PMID- 18729336
TI  - Controlled electrochemical synthesis of polypyrrole nanoparticle thin film and
      its redox transition to a highly conductive and stable polypyrrole variant.
AB  - We demonstrated here a unique method to produce a highly stable and conductive
      polypyrrole (PPY) nanoparticle film. The procedure entails controlling the redox
      switching and the electrochemical synthesis of PPY. PPY was synthesized at a very
      low forming potential or reaction rate in nonaqueous CH2Cl2 solvent to promote
      the PPY nanoparticle formation. Then its property was further optimized by first
      electrochemically reducing it at a hydrogen evolution potential in a neutral 0.1
      M NaClO4, then in a slightly acidic 0.05 M asparagine electrolyte. The PPY
      nanoparticle thin film was characterized by AFM, UV-vis and EQCM. The procedures
      described here have proven to be reproducible. The data provided by the EQCM
      shows a reversible doping and undoping mechanism of asparagine indicating the
      presence of a highly conductive PPY variant. Both UV-vis and electrochemical
      characterization suggest that the PPY film made using our approach has excellent
      redox activity as well as high stability when characterized in asparagine
      solution. The reversible doping and undoping of asparagine during redox switching
      shows great potential of these PPY nanoparticle films as biological membranes for
      a broad range of biological applications.

PMID- 18729335
TI  - Light-induced biocidal action of conjugated polyelectrolytes supported on
      colloids.
AB  - A series of water soluble, cationic conjugated polyelectrolytes (CPEs) with
      backbones based on a poly(phenylene ethynylene) repeat unit structure and
      tetraakylammonium side groups exhibit a profound light-induced biocidal effect.
      The present study examines the biocidal activity of the CPEs, correlating this
      activity with the photophysical properties of the polymers. The photophysical
      properties of the CPEs are studied in solution, and the results demonstrate that
      direct excitation produces a triplet excited-state in moderate yield, and the
      triplet is shown to be effective at sensitizing the production of singlet oxygen.
      Using the polymers in a format where they are physisorbed or covalently grafted
      to the surface of colloidal silica particles (5 and 30 microm diameter), we
      demonstrate that they exhibit light-activated biocidal activity, effectively
      killing Cobetia marina and Pseudomonas aeruginosa. The light-induced biocidal
      activity is also correlated with a requirement for oxygen suggesting that
      interfacial generation of singlet oxygen is the crucial step in the light-induced
      biocidal activity.

PMID- 18729337
TI  - Mechanism of surfactant micelle formation.
AB  - The mechanism of micelle formation of surfactants sodium dodecyl sulfate (SDS), n
      hexyldecyltrimethylammonium bromide (CTAB) and Triton X-100 (TX-100) in heavy
      water solutions was studied by 1H NMR (chemical shift and line shape) and NMR
      self-diffusion experiments. 1H NMR and self-diffusion experiments of these three
      surfactants show that their chemical shifts (delta) begin to change and resonance
      peaks begins to broaden with the increase in concentration significantly below
      their critical micelle concentrations (cmc's). At the same time, self-diffusion
      coefficients ( D) of the surfactant molecules decrease simultaneously as their
      concentrations increase. These indicate that when the concentrations are near and
      lower than their cmc's, there are oligomers (premicelles) formed in these three
      surfactant systems. Carefully examining the dependence of chemical shift and self
      diffusion coefficient on concentration in the region just slightly above their
      cmc's, one finds that the pseudophase transition model is not applicable to the
      variation of physical properties (chemical shift and self-diffusion coefficient)
      with concentration of these systems. This indicates that premicelles still exist
      in this concentration region along with the formation of micelles. The curved
      dependence of chemical shift and self-diffusion coefficient on the increase in
      concentration suggests that the premicelles grow as the concentration increases
      until a definite value when the size of the premicelle reaches that of the
      micelle, i.e., the system is likely dominated by the monomers and micelles.
      Additionally, the approximate values of premicelle coming forth concentration
      (pmc) and cmc were obtained by again fitting chemical shifts to reciprocals of
      concentrations at a different perspective, and are in good accordant with
      experimental results and literature values and prove the former conclusion.

PMID- 18729338
TI  - Particle size determination using TEM: a discussion of image acquisition and
      analysis for the novice microscopist.
AB  - As nanoparticle synthesis capabilities advance, there is an increasing need for
      reliable nanoparticle size distribution analysis. Transmission electron
      microscopy (TEM) can be used to directly image nanoparticles at scales
      approaching a single atom. However, the advantage gained by being able to "see"
      these nanoparticles comes with several tradeoffs that must be addressed and
      balanced. For effective nanoparticle characterization, the proper selection of
      imaging type (bright vs dark field), magnification, and analysis method (manual
      vs automated) is critical. These decisions control the measurement resolution,
      the contrast between the particle and background, the number of particles in each
      image, the subsequent analysis efficiency, and the proper determination of the
      particle-background boundary and affect the significance of electron beam damage
      to the sample. In this work, the relationship between the critical decisions
      required for TEM analysis of small nanoparticles and the statistical effects of
      these factors on the resulting size distribution is presented.

PMID- 18729340
TI  - Poly(dimethylsiloxane)-coated sensor devices for the formation of supported lipid
      bilayers and the subsequent study of membrane interactions.
AB  - The development of smooth hydrophilic surfaces that act as substrates for
      supported lipid bilayers (SLBs) is important for membrane studies in biology and
      biotechnology. In this article, it is shown that thin films of
      poly(dimethylsiloxane) (PDMS) formed on a sensor surface can be used as a
      substrate for the deposition of reproducible and homogeneous zwitterionic SLBs by
      the direct fusion of vesicles. Poly(dimethylsiloxane) solution (1% w/v) was spin
      coated on Love acoustic wave and surface plasmon resonance devices to form a thin
      PDMS layer. Acoustic, fluorescence, and contact angle measurements were used for
      the optimization of the PDMS film properties as a function of plasma etching
      time; parameters of interest involve the thickness and hydrophilicity of the film
      and the ability to induce the formation of homogeneous SLBs without adsorbed
      vesicles. The application of PDMS-coated sensor devices to the study membrane of
      interactions was demonstrated during the acoustic and fluorescence detection of
      the binding of melittin and defensin Crp4 peptides to model supported lipid
      bilayers.

PMID- 18729339
TI  - Sorption and desorption of phenanthrene onto iron, copper, and silicon dioxide
      nanoparticles.
AB  - The sorption and desorption of phenanthrene by three engineered nanoparticles
      including nanosize zerovalent iron (NZVI), copper (NZVC), and silicon dioxide
      (NSiO2) were investigated. The sorption of phenanthrene onto NSiO2 was linear and
      reversible due to the hydrophilic properties of NSiO2. In comparison, sorption of
      phenanthrene onto NZVI and NZVC was nonlinear and irreversible, which was
      potentially due to the existence of significantly heterogeneous surface energy
      distribution patterns detected by a standard molecular probe technique.
      Naphthalene exerted significant competitive sorption with phenanthrene for NZVI
      and NZVC, and the isotherm of phenanthrene changed from being significantly
      nonlinear to nearly linear when naphthalene was simultaneously absorbed. A
      surface adsorption mechanism was proposed to explain the observed sorption and
      competition of phenanthrene on both NZVI and NZVC. In contrast, no competition
      was observed for sorption onto NSiO2. The sorption of phenanthrene on all three
      nanoparticles significantly decreased with increasing pH. The sorption
      irreversibility of phenanthrene on NZVI and NZVC were significantly enhanced with
      decreasing pH. A pH-dependent hydrophobic effect and dipole interactions between
      the charged surface (electron acceptors) and phenanthrene with electron-rich pi
      systems (electron donors) were proposed to explain the observed pH-dependent
      sorption.

PMID- 18729341
TI  - Extracting covalent and ionic structures from usual delocalized wave functions:
      the electron-expansion methodology.
AB  - We present easily programmable expansions, allowing the calculation of the
      weights of local covalent and ionic structures of a chemical bond from usual
      delocalized wave functions; they are obtained in the framework of the electron
      expansion methodology, in which the hole conditions (involved by definition in a
      covalent or ionic structure) are expanded in terms involving only electrons. From
      the derived relations, true for both HF and correlated levels, one can also
      express the covalency/ionicity and the localization of a usual two-electron two
      center (2e/2c) bond in terms of electronic populations. The three-electron
      populations are crucial for bond localization. On the contrary, in 2e/2c bonding,
      and particularly in Charge-Shift bonds (which show enhanced covalent-ionic
      interactions) although the three-electron populations can be non-negligible, they
      are not important for the covalency/ionicity of these bonds. Numerical
      applications and discussion are given for correlated MO wave functions of
      butadiene, hexatriene, and pyrrole molecules on the basis of both natural atomic
      orbitals (NAOs) (orthogonal orbitals) and pre-NAOs (nonorthogonal orbitals).

PMID- 18729342
TI  - Theoretical study on the phenyl torsional potentials of trans
      diphenyldiphosphene.
AB  - The phenyl torsional potentials of trans-diphenyldiphosphene ( trans
      phosphobenzene; t-DPP), which is an analogue of trans-azobenzene ( t-AZB), have
      been examined by means of ab initio complete active space self-consistent field
      (CASSCF) calculations. Though the electronic structures of t-DPP are similar to
      those of t-AZB, the phenyl torsional potentials are different from each other. In
      S 0, the potential energy curve of t-DPP has double minima at nonplanar
      conformations with C 2 and C i symmetries, while that of t-AZB has only minimum
      at a planar conformation with C 2 h . In S 1, the phenyl torsion of t-AZB is
      impeded from a planar geometry more than that in S 0. On the other hand, the
      phenyl torsion of t-DPP is promoted so that the phenyl groups are perpendicularly
      twisted against the PP double bond around the Franck-Condon region. Comments on
      the experimental findings of realistic diphosphenes protected by bulky
      substituents are also made.

PMID- 18729343
TI  - Probing intramolecular interactions in arylselenides using a property descriptor
      based approach.
AB  - Although a large volume of experimental evidence is available on the existence of
      intramolecular nonbonding interactions between chalcogen atoms in main group
      organometallic compounds, the primary focus has been on the contact distances
      involving the chalcogen atoms. The important class of intramolecular Se...X
      (where X is O, S, N) nonbonding interaction in a series of organoselenium
      compounds is quantified using a new scheme based on a molecular property
      descriptor. In the present study, we have employed the nucleus-independent
      chemical shift [NICS(0)] values, as a property descriptor to evaluate the
      strength of exocyclic nonbonding interactions in a series of aryl selenides. The
      ab initio MP2 as well as density functional theory methods have been used in
      conjunction with Dunning's cc-pVDZ basis set. The quantified values of Se...X
      nonbonding interactions are compared with other schemes based on thermochemical
      equations such as homodesmic and ortho-para methods. The changes in NICS(0)
      values at the aryl ring center are found to be sensitive to the strength of
      exocyclic Se...X interaction.

PMID- 18729344
TI  - Self-consistent field calculations of excited states using the maximum overlap
      method (MOM).
AB  - We present a simple algorithm, which we call the maximum overlap method (MOM),
      for finding excited-state solutions to self-consistent field (SCF) equations.
      Instead of using the aufbau principle, the algorithm maximizes the overlap
      between the occupied orbitals on successive SCF iterations. This prevents
      variational collapse to the ground state and guides the SCF process toward the
      nearest, rather than the lowest energy, solution. The resulting excited-state
      solutions can be treated in the same way as the ground-state solution and, in
      particular, derivatives of excited-state energies can be computed using ground
      state code. We assess the performance of our method by applying it to a variety
      of excited-state problems including the calculation of excitation energies,
      charge-transfer states, and excited-state properties.

PMID- 18729345
TI  - Theoretical NMR spectroscopic analysis of the intramolecular proton transfer
      mechanism in ortho-hydroxyaryl (Un-)substitued Schiff bases.
AB  - Both NMR spectroscopic parameters are calculated as a function of the distance
      d(N-H) of the O...H...N subsystem of (un- or Z-) substituted ortho-hydroxyaryl
      Schiff bases, with Z = 4-OMe and 5-Cl. Typical patterns for NMR J couplings and
      magnetic shieldings, sigma(N) (or the chemical shift delta(N)), are obtained
      showing that they are reliable sensors from which one can get a deeper insight on
      the intramolecular proton transfer mechanism. An inflection point is found by
      representing each NMR spectroscopic parameter as a function of d(N-H) or when the
      correlation between both parameters is depicted. The analysis of these (cubic)
      functions shows whether the proton is bound to the oxygen or to the nitrogen atom
      or is shared by both atoms. In line with these findings, it is possible to
      predict the position of the proton in the bridge. These theoretical findings are
      supported by previous experimental measurements. It is shown that nitrogen
      chemical shift is quite sensitive to substituent effects though (1) J( (15)NH) is
      not. This last parameter depends on d(NH). When correlating both spectroscopic
      parameters, a previous delta(N) vs (1) J( (15)NH) linear dependence is
      generalized to a cubic dependence which seems to be more reliable. Calculations
      are based on two state of the art methodologies: DFT-B3LYP and polarization
      propagators at second order of approach (SOPPA) with large enough basis sets.

PMID- 18729346
TI  - Radicals produced by gamma-irradiation of hyperquenched glassy water containing
      2'-deoxyguanosine-5'-monophosphate.
AB  - Hyperquenched glassy water (HGW) has been suggested as the best model for liquid
      water, to be used in low-temperature studies of indirect radiation effects on
      dissolved biomolecules (Bednarek et al. J. Am. Chem. Soc. 1996, 118, 9387). In
      the present work, these effects are examined by X-band electron spin resonance
      spectroscopy (ESR) in gamma-irradiated HGW matrix containing 2'-deoxyguanosine-5'
      monophosphate. Analysis of the complex ESR spectra indicates that, in addition to
      OH(*) and HO2(*) radicals generated by water radiolysis, three species are
      trapped at 77 K:(i) G(C8)H(*) radical, the H-adduct to the double bond at C8;
      (ii) G(- *) radical anion, the product of electron scavenging by the aromatic
      ring of the base; and (iii) dR(-H)(*) radicals formed by H abstraction from the
      sugar moiety, predominantly at the C'5 position. We discuss the yields of the
      radicals, their thermal stability and transformations, as well as the effect of
      photobleaching. This study confirms our earlier suggestion that in HGW the H atom
      addition/abstraction products are created at 77 K in competition with HO2(*)
      radicals, in a concerted process following ionization of water molecule at L-type
      defect sites of the H-bonded matrix. The lack of OH(*) reactivity toward the
      solute suggests that the H-bonded structure in HGW is much more effective in
      recombining OH(*) radicals than that of aqueous glasses obtained from highly
      concentrated electrolyte solutions. Furthermore, complementary experiments for
      the neat matrix have provided evidence that HO2(*) radicals are not the product
      of H atom reaction with molecular oxygen, possibly generated by ultrasounds used
      in the process of sample preparation.

PMID- 18729347
TI  - Infrared spectroscopy of [XFeC24H12]+ (X = C5H5, C5(CH3)5) complexes in the gas
      phase: experimental and computational studies of astrophysical interest.
AB  - We report the first experimental mid-infrared (700-1600 cm (-1)) multiple-photon
      dissociation (IRMPD) spectra of [XFeC 24H 12] (+) (X = C 5H 5 or Cp, C 5(CH 3) 5
      or Cp*) complexes in the gas phase obtained using the free electron laser for
      infrared experiments. The experimental results are complemented with theoretical
      infrared (IR) absorption spectra calculated with methods based on density
      functional theory. The isomers in which the XFe unit is coordinated to an outer
      ring of C 24H 12 (+) (Out isomers) were calculated to be the most stable ones.
      From the comparison between the experimental and calculated spectra, we could
      derive that, (i) for [CpFeC 24H 12] (+) complexes, the (1)A Out isomer appears to
      be the best candidate to be formed in the experiment but the presence of the (1)A
      In higher energy isomer in minor abundance is also plausible; and (ii) for
      [Cp*FeC 24H 12] (+) complexes, the three calculated Out isomers of similar energy
      are likely to be present simultaneously, in qualitative agreement with the
      observed dissociation patterns. This study also emphasizes the threshold effect
      in the IRMPD spectrum below which IR bands cannot be observed and evidence strong
      mode coupling effects in the [XFeC 24H 12] (+) species. The effect of the
      coordination of Fe in weakening the bands of C 24H 12 (+) in the 1000-1600 cm (
      1) region is confirmed, which is of interest to search for such complexes in
      interstellar environments.

PMID- 18729348
TI  - Inactivation of NF-kappaB components by covalent binding of (-)
      dehydroxymethylepoxyquinomicin to specific cysteine residues.
AB  - Previously, we designed and synthesized a potent NF-kappaB inhibitor, DHMEQ.
      Although DHMEQ showed potent anti-inflammatory and anticancer activities in
      animals, its molecular target has not been elucidated. In the present study, its
      target protein was found to be p65 and other Rel homology proteins. We found that
      (-)-DHMEQ bound to p65 covalently with a 1:1 stoichiometry by conducting SPR and
      MALDI-TOF MS analyses. MS analysis of the chymotrypsin-digested peptide suggested
      the binding of (-)-DHMEQ to a Cys residue. Formation of Cys/(-)-DHMEQ adduct in
      the protein was supported by chemical synthesis of the adduct. Substitution of
      specific Cys in p65 and other Rel homology proteins resulted in the loss of (-)
      DHMEQ binding. (-)-DHMEQ is the first NF-kappaB inhibitor that was proven to bind
      to the specific Cys by chemical methodology. These findings may explain the
      highly selective inhibition of NF-kappaB and the low toxic effect of (-)-DHMEQ in
      cells and animals.

PMID- 18729349
TI  - Synthesis and biological evaluation of 2-amino-3-(4-chlorobenzoyl)-4-[N
      (substituted) piperazin-1-yl]thiophenes as potent allosteric enhancers of the A1
      adenosine receptor.
AB  - The synthesis and evaluation of a series of 2-amino-3-(4-chlorobenzoyl)-4-[4
      (alkyl/aryl)piperazin-yl]thiophene derivatives as allosteric enhancers of the A 1
      adenosine receptor are described. The nature of substituents on the phenyl ring
      tethered to the piperazine seem to exert a fundamental influence on the
      allosteric enhancer activity, with the 4-chlorophenyl 8f and 4-trifluoromethyl 8j
      derivatives being the most active compounds in binding (saturation and
      displacement experiments) and functional cAMP studies.

PMID- 18729350
TI  - Anxiolytic-like effects of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides by
      modulation of translocator protein promoting neurosteroid biosynthesis.
AB  - Novel N,N-disubstituted indol-3-ylglyoxylamides (1-56), bearing different
      combinations of substituents R 1-R 5, were synthesized and evaluated as ligands
      of the translocator protein (TSPO), the 18 kDa protein representing the minimal
      functional unit of the "peripheral-type benzodiazepine receptor" (PBR). Most of
      the new compounds showed a nanomolar/subnanomolar affinity for TSPO and
      stimulated steroid biosynthesis in rat C6 glioma cells with a potency similar to
      or higher than that of classic TSPO ligands such as PK 11195. Moreover, when
      evaluated in vivo by means of the elevated-plus-maze (EPM) paradigm in the rat,
      compound 32, the best-performing derivative in terms of TSPO affinity and
      pregnenolone production, showed clear anxiolytic effects. The results of this
      study suggested that the novel N,N-disubstituted indol-3-ylglyoxylamides may
      represent a promising class of compounds potentially suited for the treatment of
      anxiety disorders.

PMID- 18729351
TI  - Potent cationic inhibitors of West Nile virus NS2B/NS3 protease with serum
      stability, cell permeability and antiviral activity.
AB  - West Nile virus (WNV) has spread rapidly around the globe, efficiently crossing
      species from migrating birds into humans and other mammals. The viral protease
      NS2B-NS3 is important for WNV replication and recognizes dibasic substrate
      sequences common to other flaviviral proteases but different from most mammalian
      proteases. Potent inhibitors of WNV protease with antiviral activity have been
      elusive to date. We report the smallest and most potent inhibitors known for this
      enzyme, cationic tripeptides with nonpeptidic caps at the N-terminus and aldehyde
      at the C-terminus. One of these, compound 3 ( Ki = 9 nM) is stable in serum (>90%
      intact after 3 h, 37 degrees C), cell permeable, and shows antiviral activity (IC
      50 1.6 microM) without cytotoxicity (IC 50 >400 microM), thereby validating the
      approach of inhibiting WNV protease to suppress WNV replication.

PMID- 18729352
TI  - Isocyanide ligands adsorbed on metal surfaces: applications in catalysis,
      nanochemistry, and molecular electronics.
AB  - Knowledge of the coordination chemistry and reactivity of isocyanide ligands in
      transition-metal complexes forms the basis for understanding the adsorption and
      reactions of isocyanides on metal surfaces. In this overview, we explore
      reactions (often catalytic) of isocyanides adsorbed on metal surfaces that
      reflect their patterns of reactivity in metal complexes. We also examine
      applications of isocyanide adsorption to the stabilization of metal
      nanoparticles, the functionalization of metal electrodes, and the creation of
      conducting organic-metal junctions in molecule-scale electronic devices.

PMID- 18729354
TI  - Formation of a coordinated 2-aminoethylidene ligand and its rearrangement by
      deprotonation into a phosphinoallyl ligand containing a pyrrolidin-2-yl ring.
AB  - The activation of 1,1-diphenyl-2-propyn-1-ol by the metallic fragment [(eta (5)-C
      5Me 5)Ru(dippae)] (+) {dippae = 1,2-bis[(diisopropylphosphanyl)amino]ethane},
      followed by dehydration, produces a cationic complex that, by deprotonation and
      rearrangement, leads to a neutral complex with a phosphinoallyl ligand containing
      a pyrrolidin-2-yl ring.

PMID- 18729353
TI  - Use of YbIII-centered near-infrared (NIR) luminescence to determine the hydration
      state of a 3,2-HOPO-based MRI contrast agent.
AB  - The synthesis, structure, and characterization of a [Yb(Tren-Me-3,2-HOPO)(H 2O)
      2] complex are reported. As a result of its Yb (III) emission in the near
      infrared region, sensitized by the Me-3,2-HOPO chromophore, this complex can be
      utilized for the first time to determine the hydration state, q, via the
      luminescence lifetimes and hence the solution structure of these Me-3,2-HOPO-type
      ligands, which have attracted significant interest in complex with Gd (III) as
      possible next-generation magnetic resonance imaging contrast agents.

PMID- 18729355
TI  - Investigation of layered double hydroxides intercalated by oxomolybdenum
      catecholate complexes.
AB  - Oxomolybdenum(VI) complexes of 3,4-dihydroxybenzoic acid (3,4-H 2dhb) have been
      incorporated into layered double hydroxides (LDHs) by treatment of the LDH
      nitrate (Zn-Al, Mg-Al) or LDH-chloride (Li-Al) precursors with aqueous or
      water/ethanol solutions of the complex (NMe 4) 2[MoO 2(3,4-dhb) 2].2H 2O at 50 or
      100 degrees C. The texture and chemical composition of the products were
      investigated by elemental analysis and scanning electron microscopy (SEM) with
      coupled energy dispersive spectroscopy (EDS). Microanalysis for N and EDS
      analysis for Cl showed that at least 90% of nitrate or chloride ions were
      replaced during the ion exchange reactions. The final Mo content in the materials
      varied between 6.5 and 11.6 wt %. Mo K-edge EXAFS analysis, supported by IR,
      Raman, UV-vis, and (13)C{ (1)H} CP/MAS NMR spectroscopic studies, showed the
      presence of cointercalated [MoO 2(3,4-dhb) 2] ( m- ) and [Mo 2O 5(3,4-dhb) 2] ( m
      ) complexes in proportions that depend on the type of LDH support and the
      reaction conditions. The binuclear bis(catecholate) complex, with a Mo...Mo
      separation of 3.16 A, was the major species intercalated in the Zn-Al and Li-Al
      products prepared using only water as solvent. The X-ray powder diffraction
      (XRPD) patterns of all the Mo-containing LDHs showed the formation of an expanded
      phase with a basal spacing around 15.4 A. High-resolution synchrotron XRPD
      patterns were indexed with hexagonal unit cells with a c-axis of either 30.7 (for
      Li-Al-Mo LDHs) or 45.9 A (for a Zn-Al-Mo LDH). Fourier maps ( F obs) calculated
      from the integrated intensities extracted from Le Bail profile decompositions
      indicated that the binuclear guest species are positioned such that the Mo --> Mo
      vector is parallel to the host layers, and the overall orientation of the complex
      is perpendicular to the same layers. The thermal behavior of selected materials
      was studied by variable-temperature XRPD, thermogravimetric analysis (TGA), and
      differential scanning calorimetry (DSC).

PMID- 18729356
TI  - Syntheses, characterization, and photochromic studies of spirooxazine-containing
      2,2'-bipyridine ligands and their zinc(II) thiolate complexes.
AB  - A series of photochromic spirooxazine-containing zinc(II) diimine bis-thiolate
      complexes were successfully synthesized, and their photophysical and photochromic
      properties were studied. The X-ray crystal structure of complex 1a has also been
      determined. Upon excitation by UV light at 330 nm, all the ligands and complexes
      exhibit photochromic behavior. The thermal bleaching kinetics of the ligands and
      the complexes were studied in dimethylformamide at various temperatures. The
      photochemical quantum yields for the photochromic reactions of the ligands and
      complexes were also determined.

PMID- 18729357
TI  - Nanosolids, slushes, and nanoliquids: characterization of nanophases in metal
      clusters and nanoparticles.
AB  - One of the keys to understanding the emergent behavior of complex materials and
      nanoparticles is understanding their phases. Understanding the phases of
      nanomaterials involves new concepts not present in bulk materials; for example,
      the phases of nanoparticles are quantum mechanical even when no hydrogen or
      helium is present. To understand these phases better, molecular dynamics (MD)
      simulations on size-selected particles employing a realistic analytic many-body
      potential based on quantum mechanical nanoparticle calculations have been
      performed to study the temperature-dependent properties and melting transitions
      of free Al n clusters and nanoparticles with n = 10-300 from 200 to 1700 K. By
      analyzing properties of the particles such as specific heat capacity (c), radius
      of gyration, volume, coefficient of thermal expansion (beta), and isothermal
      compressibility (kappa), we developed operational definitions of the solid,
      slush, and liquid states of metal clusters and nanoparticles. Applying the
      definitions, which are based on the temperature dependences of c, beta, and ln
      kappa, we determined the temperature domains of the solid, slush, and liquid
      states of the Al n particles. The results show that Al n clusters ( n <or= 18,
      diameter of less than 1 nm) are more like molecules, and it is more appropriate
      to say that they have no melting transition, but Al n nanoparticles ( n >or= 19,
      diameter of more than 1 nm) do have a melting transition and are in the liquid
      state above 900-1000 K. However, all aluminum nanoparticles have a wide
      temperature interval corresponding to the slush state in which the solid and
      liquid states coexist in equilibrium, unlike a bulk material where coexistence
      occurs only at a single temperature (for a given pressure). The commonly accepted
      operational marker of the melting temperature, namely, the peak position of c, is
      not unambiguous and not appropriate for characterizing the melting transition for
      aluminum particles with the exception of a few particle sizes that have a single
      sharp peak (as a function of temperature) in each of the three properties, c,
      beta, and ln kappa.

PMID- 18729358
TI  - Fermi level engineering of single-walled carbon nanotubes by AuCl3 doping.
AB  - We investigated the modulation of optical properties of single-walled carbon
      nanotubes (SWCNTs) by AuCl 3 doping. The van Hove singularity transitions (E 11
      (S), E 22 (S), E 11 (M)) in absorption spectroscopy disappeared gradually with an
      increasing doping concentration and a new peak appeared at a high doping
      concentration. The work function was downshifted up to 0.42 eV by a strong charge
      transfer from the SWCNTs to AuCl 3 by a high level of p-doping. We propose that
      this large work function shift forces the Fermi level of the SWCNTs to be located
      deep in the valence band, i.e., highly degenerate, creating empty van Hove
      singularity states, and hence the work function shift invokes a new asymmetric
      transition in the absorption spectroscopy from a deeper level to newly generated
      empty states.

PMID- 18729359
TI  - Binding of ADP in the mitochondrial ADP/ATP carrier is driven by an electrostatic
      funnel.
AB  - The ADP/ATP carrier (AAC) is a membrane protein of paramount importance for the
      energy-fueling function of the mitochondria, transporting ADP from the
      intermembrane space to the matrix and ATP in the opposite direction. On the basis
      of the high-resolution, 2.2-A structure of the bovine carrier, a total of 0.53
      micros of classical molecular dynamics simulations were conducted in a realistic
      membrane environment to decipher the early events of ADP (3-) translocation
      across the inner membrane of the mitochondria. Examination of apo-AAC underscores
      the impermeable nature of the carrier, impeding passive transport of permeants
      toward the matrix. The electrostatic funnel illuminated from three-dimensional
      mapping of the electrostatic potential forms a privileged passageway anticipated
      to drive the diphosphate nucleotide rapidly toward the bottom of the internal
      cavity. This conjecture is verified in the light of repeated, independent
      numerical experiments, whereby the permeant is dropped near the mouth of the
      mitochondrial carrier. Systematic association of ADP (3-) to the crevice of the
      AAC, an early event in its transport across the inner membrane, is accompanied by
      the formation of an intricate network of noncovalent bonds. Simulations relying
      on the use of an adaptive biasing force reveal for the first time that the
      proposed binding site corresponds to a minimum of the free energy landscape
      delineating the translocation of ADP (3-) in the carrier. The present work paves
      the way to the design of novel nucleotides and new experiments aimed at unveiling
      key structural features in the chronology of ADP/ATP transport across the
      mitochondrial membrane.

PMID- 18729360
TI  - Mitochondria-targeted chemotherapeutics: the rational design of gold(I) N
      heterocyclic carbene complexes that are selectively toxic to cancer cells and
      target protein selenols in preference to thiols.
AB  - A family of lipophilic, cationic Au(I) complexes of N-heterocyclic carbenes
      (NHCs) have been designed as new mitochondria-targeted antitumor agents that
      combine both selective mitochondrial accumulation and selective thioredoxin
      reductase inhibition properties within a single molecule. Two-step ligand
      exchange reactions with cysteine (Cys) and selenocysteine (Sec) occur with
      release of the NHC ligands. At physiological pH the rate constants for the
      reactions with Sec are 20- to 80-fold higher than those with Cys. The complexes
      are selectively toxic to two highly tumorigenic breast cancer cell lines and not
      to normal breast cells, and the degree of selectivity and potency are optimized
      by modification of the substituent on the simple imidazolium salt precursor. The
      lead compound is shown to accumulate in mitochondria of cancer cells, to cause
      cell death through a mitochondrial apoptotic pathway and to inhibit the activity
      of thioredoxin reductase (TrxR) but not the closely related and Se-free enzyme
      glutathione reductase.

PMID- 18729362
TI  - Density functional theory calculations of hydrogen-bond-mediated NMR J coupling
      in the solid state.
AB  - A recently developed method for calculating NMR J coupling in solid-state systems
      is applied to calculate hydrogen-bond-mediated (2h) J NN couplings across intra-
      or intermolecular N-H...N hydrogen bonds in two 6-aminofulvene-1-aldimine
      derivatives and the ribbon structure formed by a deoxyguanosine derivative.
      Excellent quantitative agreement is observed between the calculated solid-state J
      couplings and those previously determined experimentally in two recent spin-echo
      magic-angle-spinning NMR studies ( Brown, S. P. ; et al. Chem. Commun. 2002, 1852
      1853 and Pham, T. N. ; et al. Phys. Chem. Chem. Phys. 2007, 9, 3416-3423 ). For
      the 6-aminofulvene-1-aldimines, the differences in (2h) J NN couplings in pyrrole
      and triazole derivatives are reproduced, while for the guanosine ribbons, an
      increase in (2h) J NN is correlated with a decrease in the N-H...N hydrogen-bond
      distance. J couplings are additionally calculated for isolated molecules of the 6
      aminofulevene-1-aldimines extracted from the crystal with and without further
      geometry optimization. Importantly, it is shown that experimentally observed
      differences between J couplings determined by solution- and solid-state NMR are
      not solely due to differences in geometry; long-range electrostatic effects of
      the crystal lattice are shown to be significant also. J couplings that are yet to
      be experimentally measured are calculated. Notably, (2h) J NO couplings across N
      H...O hydrogen bonds are found to be of a similar magnitude to (2h) J NN
      couplings, suggesting that their utilization and quantitative determination
      should be experimentally feasible.

PMID- 18729363
TI  - The long-lived nuclear singlet state of 15N-nitrous oxide in solution.
AB  - A 15N nuclear singlet lifetime of over 26 min has been observed in a solution of
      15N2O, by using a field-cycling NMR pulse sequence. This observation suggests
      applications of hyperpolarized 15N2O in medical imaging and for flow and
      diffusion studies.

PMID- 18729364
TI  - Eta2-organoazide complexes of nickel and their conversion to terminal imido
      complexes via dinitrogen extrusion.
AB  - 1-Adamantyl- and mesitylazide react with [(dtbpe)Ni]2(eta2-mu-C6H6) to give the
      eta2 organic azide adducts (dtbpe)Ni(eta2-N3R) (R = Ad, 3a; Mes, 3b) that have
      been isolated in good yields and crystallographically characterized. These azide
      adducts are intermediates in the formation of the corresponding terminal imido
      complexes (dtbpe)NiNR (R = Ad, 4a; Mes, 4b), undergoing intramolecular loss of
      dinitrogen upon mild thermolysis.

PMID- 18729365
TI  - Ethylene decomposition at undercoordinated sites on Cu(410).
AB  - We demonstrate the selective, low-temperature chemistry of ethylene on the
      strongly undercoordinated sites of Cu(410) by investigating its adsorption by
      high-resolution electron energy loss spectroscopy (HREELS), X-ray photoelectron
      spectroscopy (XPS), and temperature-programmed desorption (TPD). After dosing
      ethylene at approximately 110 K, apart from the expected pi-bonded species
      adsorbed on terraces, di-sigma-bonded ethylene and carbon are formed at the step
      edges. The latter product results from the complete dehydrogenation of ethylene
      and blocks sites for further dissociation and/or di-sigma-adsorption. However,
      these processes can be restored merely by heating the sample to 900 K, by causing
      the carbon to diffuse into the bulk. The presented results support the relevance
      of copper-based catalysts for the steam reforming process.

PMID- 18729366
TI  - Electron tomography shows molecular anchoring within a layer-by-layer film.
AB  - The layer-by-layer self-assembly of thin films consisting of alternating layers
      of DNA and bis-urea nanoribbons prevents diffusion of the components within the
      film and allows the anchoring of biotinylated molecules through molecular
      recognition in a predetermined layer of the film. Electron tomography
      demonstrates with nanometer precision the location of gold-labeled streptavidin
      bound to the incorporated biotinylated molecules.

PMID- 18729367
TI  - Highly enantioselective aza Morita-Baylis-Hillman reaction catalyzed by
      bifunctional beta-isocupreidine derivatives.
AB  - The aza-MBH reaction of imines 1 and beta-naphthyl acrylate 2 in the presence of
      C-6' modified beta-isocupreidine derivative 1c (0.1 equiv) and beta-naphthol 5
      (0.1 equiv) afforded the corresponding (3S)-aza-MBH adducts 4 in high yield and
      excellent enantiomeric excess. These catalytic conditions allowed the aliphatic
      imines to be employed for the first time as electrophilic partners of the aza-MBH
      reaction. The coexistence of two H-bond donors with different acidic strengths
      was found to be crucial for the observed high enantioselectivity.

PMID- 18729368
TI  - Activation parameters for additions of ambiphilic methoxychlorocarbene to
      alkenes.
AB  - Activation parameters are determined for the additions of methoxychlorocarbene
      (MeOCCl) to four alkenes, including tetramethylethylene (TME). MeOCCl is the
      first carbene to exhibit appreciable activation energy in addition to TME (5.8
      kcal/mol), although this reaction is still "dominated" by entropy (
      TDeltaS(double dagger) approximately 7 kcal/mol).

PMID- 18729369
TI  - Light emission of [10]cyclophenacene through energy transfer from neighboring
      carbazolylphenyl dendrons.
AB  - A dendritic deca(carbazolylphenyl)[60]fullerene bearing a cyclic benzenoid core
      was synthesized. The photophysical studies indicated that intramolecular energy
      transfer and electron transfer took place from the linked carbazolylphenyl
      moieties to the core-cyclic benzenoid moiety. The fluorescence quantum yield of
      the deca-adduct was determined to be 0.21 in toluene. Rich photophysical
      functions and their dendritic structures suggest that the photoactive decaadducts
      will serve as luminescent scaffolds in materials application.

PMID- 18729370
TI  - Efficient synthesis of substituted dihydrotetraazapentacenes.
AB  - We describe a versatile and very efficient synthesis of previously unknown
      substituted 5,14-dihydro-5,7,12,14-tetraazapentacenes (DHTAPs). A structural
      study by NMR spectroscopy showed that the conjugated pi-system of the pentacyclic
      skeleton rearranges depending on the electronic effect of the substituent(s).

PMID- 18729372
TI  - Intramolecular direct aldol reactions of sugar diketones: syntheses of
      valiolamine and validoxylamine G.
AB  - A new and stereoselective intramolecular direct aldol reaction of diketones
      derived from carbohydrates has been developed to construct carbocycles with D
      gluco-, D-galacto-, D-manno-, and L-ido-configurations. The stereochemical
      outcome of the aldol reaction of the diketone is dependent on the base used.
      Transformation of D-gluco-aldols readily affords valiolamine which also
      constitutes a formal synthesis of voglibose. Facile conversion of D-gluco
      cyclohexanones into validoxylamine G has been achieved in 12 steps with 15.1%
      overall yield from D-glucose.

PMID- 18729371
TI  - Catalyst-directed diastereoselectivity in hydrogenative couplings of acetylene to
      alpha-chiral aldehydes: formal synthesis of all eight L-hexoses.
AB  - Hydrogenative coupling of acetylene to alpha-chiral aldehydes 1a-4a using
      enantiomeric rhodium catalysts ligated by (S)-MeO-BIPHEP and (R)-MeO-BIPHEP
      delivers the diastereomeric products of carbonyl-(Z)-butadienylation 1b-4b and 1c
      4c, respectively, with good to excellent levels of catalyst directed
      diastereofacial selectivity. Diastereomeric L-glyceraldehyde acetonide adducts 1b
      and 1c were converted to the four isomeric enoates 6b, 8b, 6c, and 8c,
      representing a formal synthesis of all eight L-hexoses.

PMID- 18729373
TI  - Microbial degradation of fluometuron is influenced by roundup weatherMAX.
AB  - Laboratory experiments were conducted to describe the influence of glyphosate and
      fluometuron on soil microbial activity and to determine the effect of glyphosate
      on fluometuron degradation in soil and by Rhizoctonia solani. Soil and liquid
      medium were amended with formulated fluometuron alone or with two rates of
      formulated glyphosate. The soil carbon mineralization was measured hourly for 33
      days. The fluometuron remaining in the soil was quantified following 3, 6, 10,
      15, 20, 30, and 40 days of incubation. The fluometuron remaining in medium and
      fungal biomass was measured after 1, 3, 6, 10, 15, and 20 days of incubation. The
      addition of glyphosate with fluometuron increased C-mineralization and increased
      the rate of fluometuron degradation relative to fluometuron applied alone.
      However, more fluometuron remained in the media and less fungal biomass was
      produced when glyphosate was included.

PMID- 18729374
TI  - Transformation and sorption of fipronil in urban stream sediments.
AB  - Fipronil is an urban-use insecticide, and the increased use has led to its
      frequent detections in urban streams. Most studies on the environmental fate of
      fipronil so far have focused on soils, and little is known about its behavior in
      sediment-water systems. In this study, we investigated the transformation and
      sorption of fipronil in urban stream sediments from California, incubated under
      facultative and anaerobic conditions. Degradation of fipronil in sediments
      generally followed exponential decay kinetics, and the first-order half-lives of
      fipronil were only 4.6-18.5 days in anaerobic sediments. The persistence of
      fipronil under facultative conditions was considerably longer, with half-lives
      from 25 to 91 days. Sterilization generally decreased the dissipation of
      fipronil, indicating that microbial activity was an important factor in fipronil
      transformations in sediments. Under facultative conditions, fipronil sulfide and
      sulfone were observed, while only fipronil sulfide was detected in anaerobic
      samples. The sorption coefficient K d consistently increased with organic carbon
      contents of sediments. In the same sediment, K d usually also increased with
      contact time, suggesting decreased availability for aged residues. Results from
      this study showed that the stability of fipronil in sediments depends closely on
      the oxygen status and that due to the readily conversion of fipronil to the
      sulfone and sulfide metabolites, the overall risk assessment of fipronil in
      surface aquatic systems should take into consideration fipronil as well as its
      metabolites.

PMID- 18729375
TI  - Role of wood macromolecules on selective sorption of phenolic compounds by wood.
AB  - Wood is a complex structure of various macromolecules, mainly cellulose,
      hemicellulose, and lignin. Although the sorption process of some organic
      compounds by wood has been elucidated, the relative contribution of its different
      fractions in the sorption mechanism is not clearly determined. Certain works
      predict the amount of organic compounds sorbed on wood as a direct relationship
      to its lignin fraction. All wood macromolecules, however, seem to have the
      capacity to sorb organic compounds. Sorption of phenolic compounds on individual
      wood macromolecules has been studied and compared to that on wood. Wood-water
      partition coefficients ( K wood) for phenolic volatiles and their sorption rates
      in the presence of lignin display a linear relationship. Results show that
      cellulose and hemicellulose sorb all phenolic compounds without apparent
      distinction, whereas lignin is a selective sorbent of these compounds. Sorbant
      availability and sorbate chemical structure seem to be the key factors governing
      the sorption mechanism. Sorption kinetics study gives apparent diffusion
      coefficient values of aroma compounds, bringing new kinetic data for
      understanding the ternary system of wood, hydroalcoholic solution, and phenolic
      compounds.

PMID- 18729376
TI  - Heat stability of strawberry anthocyanins in model solutions containing natural
      copigments extracted from rose (Rosa damascena Mill.) petals.
AB  - Thermal degradation and color changes of purified strawberry anthocyanins in
      model solutions were studied upon heating at 85 degrees C by HPLC-DAD analyses
      and CIELCh measurements, respectively. The anthocyanin half-life values increased
      significantly due to the addition of rose (Rosa damascena Mill.) petal extracts
      enriched in natural copigments. Correspondingly, the color stability increased as
      the total color difference values were smaller for anthocyanins upon copigment
      addition, especially after extended heating. Furthermore, the stabilizing effect
      of rose petal polyphenols was compared with that of well-known copigments such as
      isolated kaempferol, quercetin, and sinapic acid. The purified rose petal extract
      was found to be a most effective anthocyanin-stabilizing agent at a molar
      pigment/copigment ratio of 1:2. The results obtained demonstrate that the
      addition of rose petal polyphenols slows the thermal degradation of strawberry
      anthocyanins, thus resulting in improved color retention without affecting the
      gustatory quality of the product.

PMID- 18729377
TI  - Influence of mitochondria origin on fruit quality in a citrus cybrid.
AB  - Sugar, organic acid, and carotenoid are the most important indicators of fruit
      taste and nutritional and organoleptic quality. These components were studied on
      fruit pulp of the cybrid between Willow leaf mandarin ( Citrus deliciosa Ten.)
      and Eureka lemon [ Citrus limon (L.) Burm.] and the two parents. The cybrid
      possessed nuclear and chloroplast genomes of Eureka lemon plus mitochondria from
      Willow leaf mandarin. The impact of new mitochondria on fruit quality was studied
      during the mature period. Levels of organic acids were slightly higher in the
      cybrid fruit pulp than in Eureka lemon. No significant difference in sugar and
      carotenoid content was observed between the cybrid and the lemon. Results confirm
      that the main genetic information for the biosynthesis of sugars, organic acids,
      and carotenoids is contained in the nucleus. In Citrus, cybridization can be used
      as a strategy to breed specific traits associated with mitochondrial genomes,
      such as male sterility, without affecting the main organoleptic and nutritional
      qualities.

PMID- 18729378
TI  - PI3K/AKT, JNK, and ERK pathways are not crucial for the induction of cholesterol
      biosynthesis gene transcription in intestinal epithelial cells following
      treatment with the potato glycoalkaloid alpha-chaconine.
AB  - We previously reported that exposure of the intestinal epithelial Caco-2 cell
      line to noncytotoxic concentrations of potato glycoalkaloids resulted in
      increased expression of cholesterol biosynthesis genes. Genes involved in mitogen
      activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/v-akt
      murine thymoma viral oncogene homologue (AKT) pathways and their downstream
      effectors such as Jun, c-Myc, and Fos also were induced. MAPK and PI3K/AKT
      pathways have been described to regulate the activity of sterol regulatory
      element binding transcription factors (SREBPs) and consequently the expression of
      cholesterol biosynthesis genes. In this study, to understand the mechanism of
      induction of cholesterol biosynthesis upon alpha-chaconine treatment, its effect
      on SREBP-2 protein levels was investigated. We also examined whether MAPK and
      PI3K/AKT pathways are required for the observed induction of these genes
      following exposure of cells to alpha-chaconine. Differentiated Caco-2 cells were
      pretreated with LY294002 (PI3K inhibitor), PD98059 (MEK1 inhibitor), or SP600125
      (JNK inhibitor) or a combination of all inhibitors for 24 h prior to coincubation
      with 10 microM alpha-chaconine for 6 h. Significant increases in precursor and
      mature protein levels of SREBP-2 were observed after alpha-chaconine exposure. We
      also observed that alpha-chaconine treatment resulted in significant
      phosphorylation of AKT, extracellular signal related protein kinase (ERK), and c
      jun N terminal protein kinase (JNK) but not that of p38. In general, the kinase
      inhibitor experiments revealed that phosphorylation of kinases of PI3K/AKT, ERK,
      and JNK pathways was not crucial for the induction of expression of cholesterol
      biosynthesis genes, with the exception of SC5DL. The transcription of this later
      gene was reduced when all three pathways were inhibited. On the basis of these
      results, it can be postulated that other mechanisms, which may be independent of
      the MAPK and PI3K/AKT pathways, including possibly post-translational activation
      of SREBP-2, may be more pivotal for the induction of cholesterol biosynthesis
      genes following exposure of intestinal cells to alpha-chaconine.

PMID- 18729379
TI  - Use of an in vitro digestion model to study the bioaccessibility of 4-hydroxy-2
      nonenal and related aldehydes present in oxidized oils rich in omega-6 acyl
      groups.
AB  - Mixtures of either sunflower oil or thermodegraded sunflower oil and a standard
      meal were submitted to an in vitro digestion model. The same experiment was
      carried out with fluid deep-frying fat and thermodegraded fluid deep-frying fat.
      The thermodegradation of the oil and fat was provoked by submitting them to 190
      degrees C with aeration in a convection oven, and the presence in the headspace
      of the thermodegraded oil and fat of oxygenated alpha,beta-unsaturated aldehydes
      (OalphabetaUAs), such as 4-hydroxy-2-nonenal (HNE), 4-oxo-2-nonenal (ONE), and
      4,5-epoxy-2-decenal (EDE), was monitored by solid phase microextraction (SPME)
      followed by gas chromatography-mass spectrometry (GC-MS). The digestion products
      were separated by centrifugation in a lipidic phase, an aqueous phase, and a
      pellet phase. The headspace of these three phases was also studied by SPME/GC-MS
      to check if the toxic and very reactive OalphabetaUAs above-mentioned remained
      unaltered after the in vitro digestion process or if they had reacted with the
      various compounds present in the digestion products, so disappearing from the
      samples. With the same aim the extract in ethyl acetate of the aqueous and pellet
      phases, and of the lipidic phase after dilution, were studied by GC-MS. All
      results obtained showed that a certain proportion of the toxic OalphabetaUAs
      remains unaltered after digestion, dispersed in the three phases above-mentioned,
      and thus are bioaccessible in the gastrointestinal tract and so could reach the
      systemic circulation. Compounds that may originate in Maillard type reactions (2
      pentylpyridine) are found among digestion products, proving that these reactions
      are possible in this process if adequate substrates are present. In addition, it
      has been shown that toxic metabolites from the synthetic antioxidant BHT, present
      in fat before digestion, remain unaltered after this process and could reach the
      systemic circulation.

PMID- 18729380
TI  - Recognition of cisplatin-DNA interstrand cross-links by replication protein A.
AB  - Replication protein A (RPA) is a heterotrimeric protein that is required for DNA
      replication and most DNA repair pathways. RPA has previously been shown to play a
      role in recognizing and binding damaged DNA during nucleotide excision repair
      (NER). RPA has also been suggested to play a role in psoralen DNA interstrand
      cross-link (ICL) repair, but a clear biochemical activity has yet to be
      identified in the ICL DNA repair pathways. Using HeLa cell extracts and DNA
      affinity chromatography, we demonstrate that RPA is preferentially retained on a
      cisplatin interstrand cross-link (ICL) DNA column compared with undamaged DNA.
      The retention of RPA on cisplatin intrastrand and ICL containing DNA affinity
      columns is comparable. In vitro electrophoretic mobility shift assays (EMSAs)
      using synthetic DNA substrates and purified RPA demonstrate higher affinity for
      cisplatin ICL DNA binding compared with undamaged DNA. The enhanced binding of
      RPA to the cisplatin ICL is dependent on the DNA length. As the DNA flanking the
      cisplatin ICL is increased from 7 to 21 bases, preferential RPA binding is
      observed. Fluorescence anisotropy reveals greater than 200-fold higher affinity
      to a cisplatin ICL containing 42-mer DNA compared with an undamaged DNA and a 3-4
      fold higher affinity when compared with a cisplatin intrastrand damaged DNA. As
      the DNA length and stringency of the binding reaction increase, greater
      preferential binding of RPA to cisplatin ICL DNA is observed. These data are
      consistent with a role for RPA in the initial recognition and initiation of
      cisplatin ICL DNA repair.

PMID- 18729381
TI  - Specific versus nonspecific isothermal DNA amplification through thermophilic
      polymerase and nicking enzyme activities.
AB  - Rapid isothermal nucleic acid amplification technologies can enable diagnosis of
      human pathogens and genetic variations in a simple, inexpensive, user-friendly
      format. The isothermal exponential amplification reaction (EXPAR) efficiently
      amplifies short oligonucleotides called triggers in less than 10 min by means of
      thermostable polymerase and nicking endonuclease activities. We recently
      demonstrated that this reaction can be coupled with upstream generation of
      trigger oligonucleotides from a genomic target sequence, and with downstream
      visual detection using DNA-functionalized gold nanospheres. The utility of EXPAR
      in clinical diagnostics is, however, limited by a nonspecific background
      amplification phenomenon, which is further investigated in this report. We found
      that nonspecific background amplification includes an early phase and a late
      phase. Observations related to late phase background amplification are in general
      agreement with literature reports of ab initio DNA synthesis. Early phase
      background amplification, which limits the sensitivity of EXPAR, differs however
      from previous reports of nonspecific DNA synthesis. It is observable in the
      presence of single-stranded oligonucleotides following the EXPAR template design
      rules and generates the trigger sequence expected for the EXPAR template present
      in the reaction. It appears to require interaction between the DNA polymerase and
      the single-stranded EXPAR template. Early phase background amplification can be
      suppressed or eliminated by physically separating the template and polymerase
      until the final reaction temperature has been reached, thereby enabling detection
      of attomolar starting trigger concentrations.

PMID- 18729382
TI  - Plasmodium falciparum Sir2 is an NAD+-dependent deacetylase and an acetyllysine
      dependent and acetyllysine-independent NAD+ glycohydrolase.
AB  - Sirtuins are NAD (+)-dependent enzymes that deacetylate a variety of cellular
      proteins and in some cases catalyze protein ADP-ribosyl transfer. The catalytic
      mechanism of deacetylation is proposed to involve an ADPR-peptidylimidate,
      whereas the mechanism of ADP-ribosyl transfer to proteins is undetermined. Herein
      we characterize a Plasmodium falciparum sirtuin that catalyzes deacetylation of
      histone peptide sequences. Interestingly, the enzyme can also hydrolyze NAD (+).
      Two mechanisms of hydrolysis were identified and characterized. One is
      independent of acetyllysine substrate and produces alpha-stereochemistry as
      established by reaction of methanol which forms alpha-1- O-methyl-ADPR. This
      reaction is insensitive to nicotinamide inhibition. The second solvolytic
      mechanism is dependent on acetylated peptide and is proposed to involve the
      imidate to generate beta-stereochemistry. Stereochemistry was established by
      isolation of beta-1- O-methyl-ADPR when methanol was added as a cosolvent. This
      solvolytic reaction was inhibited by nicotinamide, suggesting that nicotinamide
      and solvent compete for the imidate. These findings establish new reactions of
      wildtype sirtuins and suggest possible mechanisms for ADP-ribosylation to
      proteins. These findings also illustrate the potential utility of nicotinamide as
      a probe for mechanisms of sirtuin-catalyzed ADP-ribosyl transfer.

PMID- 18729383
TI  - Calcium, nucleotide, and actin affect the interaction of mammalian Myo1c with its
      light chain calmodulin.
AB  - To investigate the interaction of mammalian class I myosin, Myo1c, with its light
      chain calmodulin, we expressed (with calmodulin) truncation mutants consisting of
      the Myo1c motor domain followed by 0-4 presumed calmodulin-binding (IQ) domains
      (Myo1c (0IQ)-Myo1c (4IQ)). The amount of calmodulin associating with the Myo1c
      heavy chain increased with increasing number of IQ domains from Myo1c (0IQ) to
      Myo1c (3IQ). No calmodulin beyond that associated with Myo1c (3IQ) was found with
      Myo1c (4IQ) despite its availability, showing that Myo1c binds three molecules of
      calmodulin with no evidence of a fourth IQ domain. Unlike Myo1c (0IQ), the basal
      ATPase activity of Myo1c (1IQ) was >10-fold higher in Ca (2+) vs EGTA +/-
      exogenous calmodulin, showing that regulation is by Ca (2+) binding to calmodulin
      on the first IQ domain. The K m and V max of the actin-activated Mg (2+)-ATPase
      activity were largely independent of the number of IQ domains present and
      moderately affected by Ca (2+). In binding assays, some calmodulin pelleted with
      Myo1c heavy chain when actin was present, but a considerable fraction remained in
      the supernatant, suggesting that calmodulin is displaced most likely from the
      second IQ domain. The Myo1c heavy chain associated with actin in a nucleotide
      dependent fashion. In ATP a smaller proportion of calmodulin pelleted with the
      heavy chain, suggesting that Myo1c undergoes nucleotide-dependent conformational
      changes that affect the affinity of calmodulin for the heavy chain. The studies
      support a model in which Myo1c in the inner ear is regulated by both Ca (2+) and
      nucleotide, which exert their effects on motor activity through the light-chain
      binding region.

PMID- 18729384
TI  - Structural requirements for bone sialoprotein binding and modulation of matrix
      metalloproteinase-2.
AB  - Bone sialoprotein (BSP) has been shown to induce limited gelatinase activity in
      latent matrix metalloproteinase-2 (MMP-2) without removal of the propeptide and
      to restore enzymatic activity to MMP-2 previously inhibited by tissue inhibitor
      of matrix metalloproteinase-2 (TIMP2). The current study identifies structural
      domains in human BSP and MMP-2 that contribute to these interactions. The 26
      amino acid domain encoded by exon 4 of BSP is shown by a series of binding and
      activity assays to be involved in the displacement of MMP-2's propeptide from the
      active site and thereby inducing the protease activity. Binding assays in
      conjunction with enzyme activity assays demonstrate that both amino- and carboxy
      terminal domains of BSP contribute to restoration of activity to TIMP2-inhibited
      MMP-2, while the MMP-2 hemopexin domain is not required for reactivation.

PMID- 18729385
TI  - Methionine oxidation inhibits assembly and promotes disassembly of apolipoprotein
      C-II amyloid fibrils.
AB  - Methionine residues are linked to the pathogenicity of several amyloid diseases;
      however, the mechanism of this relationship is largely unknown. These diseases
      are characterized, in vivo, by the accumulation of insoluble proteinaceous
      plaques, of which the major constituents are amyloid fibrils. In vitro,
      methionine oxidation has been shown to modulate fibril assembly in several well
      characterized amyloid systems. Human apolipoprotein (apo) C-II contains two
      methionine residues (Met-9 and Met-60) and readily self-assembles in vitro to
      form homogeneous amyloid fibrils, thus providing a convenient system to examine
      the effect of methionine oxidation on amyloid fibril formation and stability.
      Upon oxidation of the methionine residues of apoC-II with hydrogen peroxide,
      fibril formation was inhibited. Oxidized apoC-II molecules did not inhibit native
      apoC-II assembly, indicating that the oxidized molecules had a reduced ability to
      interact with the growing fibrils. Single Met-Val substitutions were performed
      and showed that oxidation of Met-60 had a more significant inhibitory effect than
      oxidation of Met-9. In addition, Met-Gln substitutions designed to mimic the
      effect of oxidation on side chain hydrophilicity showed that a change in
      hydrophobicity at position 60 within the core region of the fibril had a potent
      inhibitory effect. The oxidation of preformed apoC-II fibrils caused their
      dissociation; however, mutants in which the Met-60 was substituted with a valine
      were protected from this peroxide-induced dissociation. This work highlights an
      important role for methionine in the formation of amyloid fibril structure and
      gives new insight into how oxidation affects the stability of mature fibrils.

PMID- 18729386
TI  - HIV-1 nucleocapsid protein NCp7 and its RNA stem loop 3 partner: rotational
      dynamics of spin-labeled RNA stem loop 3.
AB  - The tumbling dynamics of a 20-mer HIV-1 RNA stem loop 3 spin-labeled at the 5'
      position were probed in the nanosecond time range. This RNA interacted with the
      HIV-1 nucleocapsid Zn-finger protein, 1-55 NCp7, and specialized stopped-flow EPR
      revealed concomitant kinetics of probe immobilization from milliseconds to
      seconds. RNA stem loop 3 is highly conserved in HIV, while NCp7 is critical to
      HIV-RNA packaging and annealing. The 5' probe did not perturb RNA melting or the
      NCp7/RNA interaction monitored by gel shift and fluorescence. The 5'-labeled RNA
      tumbled with a subnanosecond isotropic correlation time (approximately 0.60 ns at
      room temperature) reflecting both local viscosity-independent bond rotation of
      the probe and viscosity-dependent diffusion of 40-60% of the RNA. The binding of
      NCp7 to spin-labeled RNA stem loop 3 in a 1:1 ratio increased the spin-labeled
      tumbling time by about 40%. At low ionic strength with a ratio of NCp7 to RNA
      >or=3 (i.e., an NCp7 to nucleotide ratio <or=7, which is the threshold ratio for
      chaperone effects), the probe tumbling time markedly increased to several
      nanoseconds, signifying a NCP7/RNA complex with restricted motion even at the
      initially mobile 5' position. Increasing the ionic strength to shield the
      electrostatic attraction between polyanionic RNA and polycationic NCp7 eliminated
      this immobilization. Forming the immobilized >or=3:1 complex also required intact
      Zn fingers. Stopped-flow EPR kinetics with NCP7/RNA mixed at a 4:1 ratio showed
      the major phase of NCp7 interaction with RNA stem loop 3 occurred within 4 ms, a
      second phase occurred with a time constant of approximately 30 ms, and a slower
      immobilization, possibly concomitant with large complex formation, proceeded over
      seconds. This work points the way for spin-labeling to investigate
      oligonucleotide-protein complexes, notably those lacking precise stoichiometry,
      that are requisite for viral packaging and genome fabrication.

PMID- 18729387
TI  - Glycosylation analysis of IgLON family proteins in rat brain by liquid
      chromatography and multiple-stage mass spectrometry.
AB  - IgLON family proteins, including limbic-associated membrane protein (LAMP),
      opioid-binding cell adhesion molecule (OBCAM), neurotrimin, and Kilon, are
      immunoglobulin (Ig) superfamily cell adhesion molecules. These molecules are
      composed of three Ig domains and a glycosylphosphatidylinositol (GPI) anchor and
      contain six or seven potential N-glycosylation sites. Although their
      glycosylations are supposed to be associated with the development of the central
      nervous system like other Ig superfamily proteins, they are still unknown because
      of difficulty in isolating individual proteins with a high degree of homology in
      performing carbohydrate analysis. In this study, we conducted simultaneous site
      specific glycosylation analysis of rat brain IgLON proteins by liquid
      chromatography and multiple-stage mass spectrometry (LC-MS ( n )). The rat brain
      GPI-linked proteins were enriched and separated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The four proteins were extracted from the
      gel, and subjected to LC-MS ( n ) after proteinase digestions. A set of
      glycopeptide MS data, including the mass spectrum, the mass spectrum in the
      selected ion monitoring mode, and the product ion spectra, was selected from all
      data based on carbohydrate-related ions in the MS/MS spectrum. The peptide
      portion and the carbohydrate structure were identified on the basis of peptide
      related ion and carbohydrate-related ions, and the accurate mass. The site
      specific glycosylations of four proteins were elucidated as follows. N-Glycans
      near the N-terminal were disialic acid-conjugated complex- and hybrid-type
      oligosaccharides. The first Ig domains were occupied by Man-5-9. Diverse
      oligosaccharides, including Lewis a/x-modified glycans, a brain-specific glycan
      known as BA-2, and Man-5, were found to be attached to the third Ig domain. Three
      common structures of glycans were found in the GPI moiety of LAMP, OBCAM, and
      neurotrimin.

PMID- 18729389
TI  - The role of intrachain and interchain interactions of regioregular poly(3
      octylthiophene) chains on the optical properties of a new amphiphilic conjugated
      random copolymer in solution.
AB  - The synthesis of a random copolymer through free radical copolymerization of a
      properly vinyl monofunctionalized regioregular poly(3-octylthiophene) (rrP3OT)
      macromonomer and N,N'-dimethylacrylamide (DMAM) is presented. The optical
      properties of the copolymer in water and in several organic solvents of varying
      polarity, as well as in THF/water and THF/methanol mixtures, were explored using
      UV-vis and photoluminescence spectroscopy. It is demonstrated that the rrP3OT
      chains adopt a coil conformation in solvents such as tetrahydrofuran (THF) and
      chloroform with the appearance of the absorption and emission maxima at 439 and
      565 nm, respectively. On the contrary, the rrP3OT chains are organized on a
      single chain packing form (intrachain interactions) in polar solvents such as
      ethanol and methanol, as it is verified with the observation of the
      characteristic three vibronic features of the absorption spectra of the copolymer
      with maxima at 513, 550, and 603 nm and emission maxima at 560 nm. However, when
      water is used as solvent, the rrP3OT chains self-assemble into a stacklike
      structure due to the increased interchain interactions, as confirmed by the
      different aggregation process of the rrP3OT chains in the THF/water mixture, the
      broader absorption spectrum in water compared to those recorded in ethanol and
      methanol, and the 80 nm red-shifted emission maximum, centered at 640 nm.

PMID- 18729390
TI  - Delamination of surfactant-intercalated brucite-like hydroxy salts of cobalt and
      copper and solvothermal decomposition of the resultant colloidal dispersions.
AB  - Surfactant anion intercalated hydroxy salts of copper and cobalt of the formula
      M(OH)2- x (surf)x.mH2O [M = Cu, Co; surf = dodecyl sulfate, dodecyl benzene
      sulfonate, and x = 0.5 for Cu and 0.67 for Co] delaminate readily in 1-butanol to
      give translucent colloidal dispersions that are stable for months. The extent of
      delamination and the colloidal dispersion observed in these solids is higher than
      what had been observed for layered double hydroxides. The dispersions yield the
      corresponding nanoparticulate oxides on solvothermal decomposition. While the
      copper hydroxy salt forms approximately 300 nm dendrimer-like CuO nanostructures
      comprising nanorods of approximately 10 nm diameter, the cobalt analogue forms
      approximately 20 nm superparamagnetic particles of Co3O4.

PMID- 18729391
TI  - The implications of stochastic synthesis for the conjugation of functional groups
      to nanoparticles.
AB  - Stochastic synthesis of a ligand coupled to a nanoparticle results in a
      distribution of populations with different numbers of ligands per nanoparticle.
      This distribution was resolved and quantified using HPLC and is in excellent
      agreement with the ligand/nanoparticle average measured by 1H NMR, gel permeation
      chromatography (GPC), and potentiometric titration, and yet significantly more
      disperse than commonly held perceptions of monodispersity. Two statistical models
      were employed to confirm that the observed heterogeneity is consistent with
      theoretical expectations.

PMID- 18729393
TI  - Al(III) hydration revisited. An ab initio quantum mechanical charge field
      molecular dynamics study.
AB  - To assess the novel quantum mechanical charge field (QMCF) molecular dynamics
      (MD) approach, two simulations of hydrated Al(III) have been carried out, as this
      system proved to be a well-suited test case for hybrid ab initio/molecular
      mechanics simulations. Two different population analysis schemes according to
      Mulliken and Lowdin have been applied to evaluate the atomic charges in the QM
      region. It is shown that the QMCF MD approach yields a substantially improved
      description of the system and that, due to the fact that solute-solvent
      potentials can be renounced, the QMCF MD framework is a more convenient approach
      to investigate solvated systems compared to conventional ab initio QM/MM MD
      approaches.

PMID- 18729392
TI  - Dark quenched matrix metalloproteinase fluorogenic probe for imaging
      osteoarthritis development in vivo.
AB  - The early detection of osteoarthritis (OA) is currently a key challenge in the
      field of rheumatology. Biochemical studies of OA have indicated that matrix
      metalloproteinase-13 (MMP-13) plays a central role in cartilage degradation. In
      this study, we describe the potential use of a dark-quenched fluorogenic MMP-13
      probe to image MMP-13 in both in vitro and rat models. The imaging technique
      involved using a MMP-13 peptide substrate, near-infrared (NIR) dye, and a NIR
      dark quencher. The results from this study demonstrate that the use of a dark
      quenched fluorogenic probe allows for the visual detection of MMP-13 in vitro and
      in OA-induced rat models. In particular, by targeting this OA biomarker, the
      symptoms of the early and late stages of OA can be readily monitored, imaged, and
      analyzed in a rapid and efficient fashion. We anticipate that this simple and
      highly efficient fluorogenic probe will assist in the clinical management of
      patients with OA, not only for early diagnosis but also to assess individual
      patient responses to new drug treatments.

PMID- 18729394
TI  - Wetting and freezing of hexadecane on an aqueous surfactant solution: triple
      point in a 2-D film.
AB  - Wetting of water by hexadecane has been investigated by ellipsometry as a
      function of the concentration of the cationic surfactant dodecyltrimethylammonium
      bromide (DTAB) in the aqueous phase and temperature. Three phases are identified:
      a 2-D gas of hexadecane molecules and DTAB molecules, a 2-D liquid comprising a
      mixed monolayer of hexadecane and DTAB, and a 2-D 'solid' phase. Evidence is
      presented to support the hypothesis that the liquid-solid phase transition is
      actually a wetting transition in which a surface-frozen layer of pure hexadecane
      wets the liquid-like mixed monolayer of hexadecane and DTAB. The triple point, at
      which the three phases coexist, is located at a temperature of 17.3 degrees C and
      DTAB concentration of 0.75 mmol kg (-1). The slopes of the three phase boundaries
      are analyzed thermodynamically.

PMID- 18729395
TI  - Carbohydrate-carbohydrate interaction prominence in 3D supramolecular self
      assembly.
AB  - Self-association in water of biologically significant carbohydrate molecules is a
      controversial topic due to the strong solvation of these molecules in this
      solvent and the difficulty to experimentally detect these very weak
      intermolecular forces by biophysical techniques. Herein we report the tremendous
      ability of amphiphilic carbohydrate molecules to form complex three-dimensional
      architectures. We have experimentally observed the 3D self-assembly into
      multilayers of disaccharide neoglycolipid dimers on graphite by means of
      noncontact AFM and we have also theoretically modeled the interaction between two
      dimers in order to learn about the structure and composition of these layers. A
      simple bilayer structure as observed for many amphiphilic lipids was discarded by
      the experiments. Instead, based on the good agreement between experiments and
      calculations, we propose that multilayer formation takes place through the
      assembly of building blocks consisting of two dimers each. The fundamental key in
      the formation of this supramolecular structure is the complementarity between the
      van der Waals surfaces of the amphiphilic carbohydrate molecules, a result which
      differs from the most common idea that H-bonding interactions are prominent in
      carbohydrate-mediated interactions.

PMID- 18729396
TI  - Ionic liquid near a charged wall: structure and capacitance of electrical double
      layer.
AB  - We study the effects of ion size asymmetry and short-range correlations on the
      electrical double layer in ionic liquids: we perform molecular dynamics
      simulations of a model ionic liquid between two "electrodes" and calculate the
      differential capacitance of each as a function of the electrode potential. The
      capacitance curve has an asymmetric "bell-shape" character, in qualitative
      agreement with recent experiments and the mean- field theory (MFT) which takes
      into account the limitation on the maximal local density of ions. The short-range
      ionic correlations, not included in the MFT, lead to an overscreening effect
      which changes radically the structure of the double layer at small and moderate
      charging. With the radius of cations taken to be twice as large as anions, the
      position of the main capacitance maximum is shifted positively from the potential
      of zero charge (PZC), as predicted by MFT. An extension of the theory (EMFT),
      however, reproduces the simulated capacitance curve almost quantitatively.
      Capacitance curves for real ionic liquids will be affected by nonspherical shape
      of ions and sophisticated pair potentials, varying from liquid to liquid. But
      understanding the capacitance behavior of such model system is a basis for
      rationalizing those more specific features.

PMID- 18729397
TI  - Temperature dependence of exciton diffusion in conjugated polymers.
AB  - The temperature dependence of the exciton dynamics in a conjugated polymer is
      studied using time-resolved spectroscopy. Photoluminescence decays were measured
      in heterostructured samples containing a sharp polymer-fullerene interface, which
      acts as an exciton quenching wall. Using a 1D diffusion model, the exciton
      diffusion length and diffusion coefficient were extracted in the temperature
      range of 4-293 K. The exciton dynamics reveal two temperature regimes: in the
      range of 4-150 K, the exciton diffusion length (coefficient) of approximately 3
      nm (approximately 1.5 x 10 (-4) cm2/s) is nearly temperature independent.
      Increasing the temperature up to 293 K leads to a gradual growth up to 4.5 nm
      (approximately 3.2 x 10 (-4) cm2/ s). This demonstrates that exciton diffusion in
      conjugated polymers is governed by two processes: an initial downhill migration
      toward lower energy states in the inhomogenously broadened density of states,
      followed by temperature activated hopping. The latter process is switched off
      below 150 K.

PMID- 18729398
TI  - Pyrrolidinium-based ionic liquids. 1-Butyl-1-methyl pyrrolidinium dicyanoamide:
      thermochemical measurement, mass spectrometry, and ab initio calculations.
AB  - The standard molar enthalpy of formation of the ionic liquid 1-butyl-1
      methylpyrrolidinium dicyanamide has been determined at 298 K by means of
      combustion calorimetry, while the enthalpy of vaporization and the mass spectrum
      of the vapor (ion pairs) have been determined by temperature-programmed
      desorption and line of sight mass spectrometry. Ab initio calculations for 1
      butyl-1-methylpyrrolidinium dicyanamide have been performed using the G3MP2 and
      CBS-QB3 theory, and the results from homodesmic reactions are in excellent
      agreement with the experiments.

PMID- 18729399
TI  - Chromonic liquid crystal formation by Edicol Sunset Yellow.
AB  - The solution and liquid crystalline phases formed by dissolution of the dye
      Edicol Sunset Yellow (ESY) in water have been examined using optical microscopy,
      multinuclear NMR (1H, 2H, 13C, 23Na), and X-ray diffraction. From the solution 1H
      and 13C spectra (particularly 13C), it is clear that the tautomeric form present
      in all these phases is the hydrazone, NH, structure, not the usually given azo,
      OH, form. Two chromonic mesophases occur: a nematic (N) phase at approximately 30
      40 wt % and a hexagonal (M) phase at approximately 40-45 wt %. X-ray diffraction
      data show that the aggregates in the mesophases are single molecule stacks, with
      a typical spacing of approximately 3.5 angstroms, as expected for these systems.
      The NMR quadrupole splittings (2H2O, 23Na) are similar to those observed for
      surfactant lyotropic mesophases, suggesting that there are no water molecules or
      counter ions that are tightly bound to the ESY aggregates. An unusual feature of
      the X-ray diffraction pattern of the mesophases is the occurrence of diffuse off
      axis reflections at approximately 6.8 angstroms. It is proposed that these arise
      from a head-to-tail packing of the molecules within the stacks.

PMID- 18729400
TI  - Quantitation and differentiation of bioparticles based on the measurements of
      light-scattering signals with a common spectrofluorometer.
AB  - By simultaneously scanning both the excitation and emission monochromators of a
      common spectrofluorometer with same starting excitation and emission wavelength
      (namely, Delta lambda = 0), we obtained synchronous light scattering (SLS)
      signals that related to Rayleigh and Mie scatterings. It was found that the SLS
      signals could be applied for quantitation and differentiation of model
      bioparticles such as Saccharomyces cerevisiae, Schizosaccharomyces pombe,
      Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Bacillus
      thuringiensis and Bacillus megaterium. In PBS buffer, these model bioparticles
      could form colloidal suspensions or dispersions of sizes ranging from hundreds of
      nanometers to tens of micrometers, giving SLS signals with the intensity being
      proportional to the amount of bioparticles in the range from 1.7 x 10 (5) to 1.7
      x 10 (9) CFU/mL. A further finding is that polarized synchronous light scattering
      (PSLS) signals of I 0 degrees -30 degrees against I 0 degrees -0 degrees , which
      could be obtained by introducing polarizing sheets accessory of the
      spectrofluorometer, and the derivative synchronous light scattering (DrSLS)
      signals, which could be obtained directly with the extension function of the
      spectrofluorometer, offer differentiation information of bioparticles connected
      with their size, shape, refractive indexes, and inner structure. Refractive
      indexes of spherical bacteria were then calculated based on light scattering
      signals.

PMID- 18729401
TI  - Single-chain and aggregation properties of semiconducting polymer solutions
      investigated by coarse-grained langevin dynamics simulation.
AB  - A coarse-grained (CG) model and Langevin dynamics scheme are proposed to
      investigate the material properties in dilute solution of a model semiconducting
      conjugated polymer, poly(2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene)
      (MEH-PPV). While the intra- and intermolecular potentials for the CG particle
      (currently, a monomer unit) were determined from the molecular dynamics (MD)
      simulation of a united atomistic model, fluctuation-dissipation forces arising
      from the treatment of a solvent field were self-consistently constructed from the
      measured particle diffusivity in a given solvent (i.e., chloroform or toluene)
      through the atomistic MD simulation. It is shown that the resultant Langevin
      dynamics simulation, which is substantially more efficient than the counterpart
      MD simulation of the same CG model, is able to capture the dynamic (such as
      center-of-mass diffusivity) as well as the structural (such as radius of
      gyration) features of the investigated polymer solutions. Essential material
      properties that can now be directly studied include the following: Scaling
      exponents for estimating the exact solvent qualities were, for the first time,
      determined for the two solvent systems investigated; the persistence length
      obtained was also noted to be in excellent agreement with early experimental
      estimations. Preliminary observations on the supramolecular aggregation
      properties were in good agreement with the general observations from a wide range
      of recent experiments, and shed light on the essential impact of solvent quality
      on the supramolecular aggregation structures.

PMID- 18729402
TI  - On the inner structure and topology of clusters in two-component lipid bilayers.
      Comparison of monomer and dimer Ising models.
AB  - It has been shown on model and biological systems that membrane clusters can
      affect in-plane membrane reactions and can control biochemical reaction cascades.
      Clusters of two-component phospholipid bilayers have been simulated by two Ising
      type lattice models: the monomer and the dimer model. In each model the plane of
      one layer of the bilayer is represented by a triangular lattice, each site of
      which is occupied by an acyl chain of either a component 1 or a component 2 lipid
      molecule. The dimer model assumes that pairs of acyl chains (lipid molecules) are
      permanently connected, forming dimers on the lattice, while in the case of the
      monomer model this covalent connection between acyl chains is ignored. Phase
      diagrams of two-component phospholipid bilayers were successfully calculated by
      both models. In this work, we use Monte Carlo techniques to calculate
      thermodynamic averages of global and local characteristics of the largest
      component 2 cluster (such as outer/inner perimeter, percolation, minimal linear
      size, and local density) and compare the results obtained by the two models. A
      new method is developed to characterize the inner structure of the clusters. Each
      point of a cluster is classified based on its shortest distance (or depth) from
      the cluster's outer perimeter. Then local cluster properties, such as density,
      are calculated as a function of the depth. The depth analysis reveals that toward
      the cluster interior the average density usually decreases in midsize clusters
      and remains constant in very large clusters. On the basis of the simulations the
      following typical cluster topologies are identified at different cluster sizes
      and cooperativity parameter values: (i) branch-like, (ii) circular, (iii) band
      like, and (iv) planar.We did not find qualitative differences between the cluster
      structures in the dimer and monomer model. However, at the same cluster size and
      cooperativity parameter value the cluster of the dimer model is more compact. The
      cluster properties of the dimer model are different from that of the monomer
      model because of the lower mixing entropy and higher formation energy of an
      elementary inner island.

PMID- 18729403
TI  - Driving forces for the mutual conversions between phenothiazines and their
      various reaction intermediates in acetonitrile.
AB  - The thermodynamic driving forces (defined as the enthalpy changes or redox
      potentials in this work) of the 18 phenothiazines and their analogues,
      phenoxazine, N-methyl-dihydrophenazine, 9H-thioxanthene, 9H-xanthene and 9,10
      dihydro- N-methylacridine, to release hydride, hydrogen atom, proton, and
      electron in acetonitrile, the thermodynamic driving forces of the radical cations
      of the phenothiazines and the analogues to release hydrogen atom, proton, and
      electron in acetonitrile, and the thermodynamic driving forces of the cations of
      the phenothiazines with two positive charges and their analogues to release
      proton in acetonitrile were estimated by using experimental methods. The effect
      of the remote substituents on the 11 determined thermodynamic driving forces were
      examined according to Brown's substituent parameters; the results show that the
      values of the 11 thermodynamic driving forces all are linearly dependent on the
      sum of Brown substituent parameters (sigma +) with very good correlation
      coefficients, which indicates that for any one- or multisubstituted at para-
      and/or meta-position phenothiazines and their various reaction intermediates, the
      11 thermodynamic driving forces all can be easily and safely estimated from the
      corresponding Brown substituent parameters (sigma +). The relative effective
      charges on the center nitrogen atom in phenothiazines and their various reaction
      intermediates were estimated from the related Hammett-type linear free-energy
      relationships, which can be used to efficiently measure the electrophilicity,
      nucleophilicity, and dimerizing ability of the corresponding reaction
      intermediates of phenothiazines and their analogues. All the information
      disclosed in this work could not only supply a gap of the chemical thermodynamics
      on the mutual conversions between phenothiazines and their various reaction
      intermediates in solution but also strongly promote the fast development of the
      chemistry and application of phenothiazines and their analogues.

PMID- 18729404
TI  - Optimal design and characterization of superparamagnetic iron oxide nanoparticles
      coated with polyvinyl alcohol for targeted delivery and imaging.
AB  - Superparamagnetic iron oxide nanoparticles (SPION) with narrow size distribution
      and stabilized by polyvinyl alcohol (PVA) were synthesized. The particles were
      prepared by a coprecipitation technique using ferric and ferrous salts with a
      molar Fe3+/Fe2+ ratio of 2. Using a design of experiments (DOE) approach, the
      effect of different synthesis parameters (stirring rate and base molarity) on the
      structure, morphology, saturation magnetization, purity, size, and size
      distribution of the synthesized magnetite nanoparticles was studied by various
      analysis techniques including X-ray powder diffraction (XRD), thermogravimetric
      analysis (TGA) with differential scanning calorimetry (DSC) measurements,
      vibrating-sample magnetometer (VSM), transmission electron microscopy (TEM), UV
      visible, and Fourier transform infrared (FT-IR) spectrometer. PVA not only
      stabilized the colloid but also played a role in preventing further growth of
      SPION followed by the formation of large agglomerates by chemisorption on the
      surface of particles. A rich behavior in particle size, particle formation, and
      super paramagnetic properties is observed as a function of molarity and stirring
      conditions. The particle size and the magnetic properties as well as particle
      shape and aggregation (individual nanoparticles, magnetic beads, and magnetite
      colloidal nanocrystal clusters (CNCs) are found to be influenced by changes in
      the stirring rate and the base molarity. The formation of magnetic beads results
      in a decrease in the saturation magnetization, while CNCs lead to an increase in
      saturation magnetization. On the basis of the DOE methodology and the resulting 3
      D response surfaces for particle size and magnetic properties, it is shown that
      optimum regions for stirring rate and molarity can be obtained to achieve coated
      SPION with desirable size, purity, magnetization, and shape.

PMID- 18729405
TI  - Effect of polarization on the opsin shift in rhodopsins. 2. Empirical
      polarization models for proteins.
AB  - The explicit treatment of polarization as a many-body interaction in condensed
      phase systems represents a current problem in empirical force-field development.
      Although a variety of efficient models for molecular polarization have been
      suggested, polarizable force fields are still far from common use nowadays. In
      this work, we consider interactive polarization models employing Thole's short
      range damping scheme and assess them for application on polypeptides. Despite the
      simplicity of the model, we find mean polarizabilities and anisotropies of amino
      acid side chains in excellent agreement with MP2/cc-pVQZ benchmark calculations.
      Combined with restrained electrostatic potential (RESP) derived atomic charges,
      the models are applied in a quantum-mechanical/molecular-mechanical (QM/MM)
      approach. An iterative scheme is used to establish a self-consistent mutual
      polarization between the QM and MM moieties. This ansatz is employed to study the
      influence of the protein polarizability on calculated optical properties of the
      protonated Schiff base of retinal in rhodopsin (Rh), bacterio-rhodopsin (bR), and
      pharaonis sensory rhodopsin II (psRII). The shifts of the excitation energy due
      to the instantaneous polarization response of the protein to the charge transfer
      on the retinal chromophore are quantified using the high level ab initio
      multireference spectroscopy-oriented configuration interaction (SORCI) method.
      The results are compared with those of previously published QM1/QM2/MM models for
      bR and psRII.

PMID- 18729406
TI  - Synthesis of C3-substituted 4-azaindoles: an easy access to 4-azamelatonin and
      protected 4-azatryptophan.
AB  - C3-Substituted-4-azaindoles were synthesized from pyridylacetonitriles in a two
      step sequence allowing the easy introduction of a range of substituents. This
      strategy permits the rapid synthesis of 4-azamelatonin and a protected 4
      azatryptophan.

PMID- 18729407
TI  - Clean and efficient benzylic C-H oxidation in water using a hypervalent iodine
      reagent: activation of polymeric iodosobenzene with KBr in the presence of
      montmorillonite-K10.
AB  - We have found that unreactive and insoluble polymeric iodosobenzene [PhIO] n
      induced aqueous benzylic C-H oxidation to effectively give arylketones, in the
      presence of KBr and montmorillonite-K10 (M-K10) clay. Water-soluble and reactive
      species 1 having the unique I(III)-Br bond, in situ generated from [PhIO]n and
      KBr, was considered to be the key radical initiator during the reactions.

PMID- 18729408
TI  - N-phosphino-p-tolylsulfinamide ligands: synthesis, stability, and application to
      the intermolecular Pauson-Khand reaction.
AB  - Here we synthesized a family of racemic and optically pure N-phosphino-p
      tolylsulfinamide (PNSO) ligands. Their stability and coordination behavior toward
      dicobalt-alkyne complexes was evaluated. Selectivities of up to 3:1 were achieved
      in the ligand exchange process with (mu-TMSC2H)Co2(CO)6. The resulting optically
      pure major complexes were tested in the asymmetric intermolecular Pauson-Khand
      reaction and yielded up to 94% ee. X-ray studies of the major complex 18a
      indicated that the presence of an aryl group on the sulfinamide reduces the
      hemilabile character of the PNSO ligands.

PMID- 18729409
TI  - Highly regioselective synthesis of polysubstituted pyrroles through three
      component reaction induced by low-valent titanium reagent.
AB  - 1,2,3,5-Tetrasubstituted and 1,2,3,4,5-pentasubstituted pyrroles may be
      synthesized through three-component reaction of 1,3-diketones, aldehydes, and
      amines induced by low-valent titanium reagent. High regioselectivity was
      achieved. Compared with the classical synthetic method, this new method has the
      advantages of short reaction time (15 min), high yields, convenient manipulation,
      and high regioselectivity.

PMID- 18729410
TI  - Plexcitonic nanoparticles: plasmon-exciton coupling in nanoshell-J-aggregate
      complexes.
AB  - Stable Au nanoshell-J-aggregate complexes are formed that exhibit coherent
      coupling between the localized plasmons of a nanoshell and the excitons of
      molecular J-aggregates adsorbed on its surface. By tuning the nanoshell plasmon
      energies across the exciton line of the J-aggregate, plasmon-exciton coupling
      energies for these complexes are obtained. The strength of this interaction is
      dependent on the specific plasmon mode of the nanoparticle coupled to the J
      aggregate exciton. From a model based on Gans theory, we obtain an expression for
      the plasmon-exciton hybridized states of the complex.

PMID- 18729411
TI  - Stepwise current-driven release of attogram quantities of copper iodide
      encapsulated in carbon nanotubes.
AB  - Encapsulated nanograins of copper iodide have been sequentially discharged from
      individual carbon nanotubes. Using a high resolution electron microscope equipped
      with a two-terminal electrical measurements unit, it was possible to manipulate
      the filling contents with precisions of a few attograms at a time. Changes in
      electrical resistance and filling ratio were followed in tandem and in real-time.
      It is shown that the pulsed release of the halide is directly related to the
      overall conductance of the filled nanotube.

PMID- 18729412
TI  - Chiral-angle distribution for separated single-walled carbon nanotubes.
AB  - Chiral indices (n, m) of metallic and semiconducting single-walled carbon
      nanotubes (SWNTs) selectively separated via the density-gradient
      ultracentrifugation process were individually assigned by using an aberration
      corrected transmission electron microscope (TEM) operated at 80 kV. Our
      statistical analysis revealed that armchair (n, n) and chiral (n, n-3) SWNTs with
      large chiral angles (>20 degrees) are dominant metallic nanotubes in the
      separated samples, whereas such a noticeable preference of particular indices was
      not observed for semiconducting nanotubes. Some significant discrepancies were
      found between the TEM and spectroscopic results on the major chiral indices and
      the metal/semiconductor ratios in these SWNTs.

PMID- 18729413
TI  - Formation of dopant-pair defects and doping efficiency in B- and P-doped silicon
      nanowires.
AB  - First-principles calculations are performed to investigate the stability of
      dopant-related defects and the dependence of doping efficiency on wire diameter
      and orientation in hydrogen-passivated silicon nanowires doped with B and P
      dopants. As the diameter decreases below a critical value, it is energetically
      more favorable for donor atoms to form donor-pair defects, which consist of two
      donors separated at the nearest-neighbor distance. While donor-pair defects are
      unstable in bulk Si, the stability of these defects is greatly enhanced because
      of the confinement effect in nanostructures, which leads to the increase of band
      gap and thereby the shallow level of a substitutional donor. As donor-pair
      defects are electrically inactive defects, the doping efficiency is expected to
      be suppressed in small-diameter wires, regardless of the presence of surface or
      interface dangling-bond defects which were previously proposed to be the
      compensating defects. In the case of B dopants, the formation of pair defects is
      unfavorable against shallow acceptor levels, in contrast to n-type dopants,
      without affecting the doping efficiency.

PMID- 18729414
TI  - Schottky solar cells based on colloidal nanocrystal films.
AB  - We describe here a simple, all-inorganic metal/NC/metal sandwich photovoltaic
      (PV) cell that produces an exceptionally large short-circuit photocurrent (>21 mA
      cm(-2)) by way of a Schottky junction at the negative electrode. The PV cell
      consists of a PbSe NC film, deposited via layer-by-layer (LbL) dip coating that
      yields an EQE of 55-65% in the visible and up to 25% in the infrared region of
      the solar spectrum, with a spectrally corrected AM1.5G power conversion
      efficiency of 2.1%. This NC device produces one of the largest short-circuit
      currents of any nanostructured solar cell, without the need for sintering,
      superlattice order or separate phases for electron and hole transport.

PMID- 18729415
TI  - Graphene-based atomic-scale switches.
AB  - Graphene's remarkable mechanical and electrical properties, combined with its
      compatibility with existing planar silicon-based technology, make it an
      attractive material for novel computing devices. We report the development of a
      nonvolatile memory element based on graphene break junctions. Our devices have
      demonstrated thousands of writing cycles and long retention times. We propose a
      model for device operation based on the formation and breaking of carbon atomic
      chains that bridge the junctions. We demonstrate information storage based on the
      concept of rank coding, in which information is stored in the relative
      conductance of graphene switches in a memory cell.

PMID- 18729417
TI  - Local heating in metal-molecule-metal junctions.
AB  - We report a technique that can be utilized as a nanoscale thermometer and its
      application to metal-molecule-metal junctions at room temperatures. We find that
      a molecular junction heats up to 463 K at 1 V. We also revealed an onset bias of
      approximately 0.04 V for heat generation via electron-phonon scattering by
      examining inelastic electron tunneling spectroscopy. The present results suggest
      the importance of attaining an optimal thermal link at molecule-electrode
      interfaces for providing practically sufficient electrical durability.

PMID- 18729416
TI  - A synthetic surface that undergoes spatiotemporal remodeling.
AB  - The ability to undergo spatially resolved remodeling within defined time domains
      is one of the ubiquitous features of nature. In fact, essentially any biological
      structure undergoes defined molecular interactions and exhibits lateral mobility
      within defined time domains. The impartment of surface mobility has therefore
      emerged as one of the key challenges, when engineering synthetic analogues of
      natural biointerfaces. Herein, we report a synthetic analogue based on self
      assembled monolayers that can undergo spatial remodeling on demand, thereby
      mimicking nature's spatiotemporally controlled biointerfaces. First, we created
      microstructured surfaces, where the structural differences between regions
      originated from differences in the molecular density of the nanofilm, while the
      chemical composition of all regions remained identical. We then demonstrated
      thermally controlled, lateral mobility of thiolates between different regions of
      density and found that there exists appropriate threshold temperatures, from
      where continuous lateral diffusion of thiolates may occur within the plane of the
      gold surface until steady-state equilibrium with an average surface density is
      reached. The ability to remodel interfaces on demand is a key characteristic of
      natural systems, which we now begin to mimic through synthetic model systems.
      Engineered biointerfaces, which can undergo spatially and temporally controlled
      remodeling, will be of utmost importance for a range of applications including
      molecular devices, biosensors, and future biomaterials.

PMID- 18729418
TI  - Carrier multiplication in semiconductor nanocrystals: theoretical screening of
      candidate materials based on band-structure effects.
AB  - Direct carrier multiplication (DCM) occurs when a highly excited electron-hole
      pair decays by transferring its excess energy to the electrons rather than to the
      lattice, possibly exciting additional electron-hole pairs. Atomistic electronic
      structure calculations have shown that DCM can be induced by electron-hole
      Coulomb interactions, in an impact-ionization-like process whose rate is
      proportional to the density of biexciton states rho XX. Here we introduce a DCM
      "figure of merit" R2(E) which is proportional to the ratio between the biexciton
      density of states rhoXX and the single-exciton density of states rhoX, restricted
      to single-exciton and biexciton states that are coupled by Coulomb interactions.
      Using R2(E), we consider GaAs, InAs, InP, GaSb, InSb, CdSe, Ge, Si, and PbSe
      nanocrystals of different sizes. Although DCM can be affected by both quantum
      confinement effects (reflecting the underly electronic structure of the confined
      dot-interior states) and surface effects, here we are interested to isolate the
      former. To this end the nanocrystal energy levels are obtained from the
      corresponding bulk band structure via the truncated crystal approximation. We
      find that PbSe, Si, GaAs, CdSe, and InP nanocrystals have larger DCM figure of
      merit than the other nanocrystals. Our calculations suggest that high DCM
      efficiency requires high degeneracy of the corresponding bulk band-edge states.
      Interestingly, by considering band structure effects we find that as the dot size
      increases the DCM critical energy E0 (the energy at which R2(E) becomes >or=1) is
      reduced, suggesting improved DCM. However, whether the normalized E0/epsilong
      increases or decreases as the dot size increases depends on dot material.

PMID- 18729419
TI  - The effect of gold nanorods on cell-mediated collagen remodeling.
AB  - Cardiac fibroblasts, the noncontractile cells of the heart, contribute to
      myocardial maintenance through the deposition, degradation, and organization of
      collagen. Adding polyelectrolyte-coated gold nanorods to three-dimensional
      constructs composed of collagen and cardiac fibroblasts reduced contraction and
      altered the expression of mRNAs encoding beta-actin, alpha-smooth muscle actin,
      and collagen type I. These data show that nanomaterials can modulate cell
      mediated matrix remodeling and suggest that the targeted delivery of
      nanomaterials can be applied for antifibrotic therapies.

PMID- 18729420
TI  - Hydroamination: direct addition of amines to alkenes and alkynes.

PMID- 18729421
TI  - Comment on "Beyond the benzene dimer: an investigation of the additivity of pi-pi
      interactions".

PMID- 18729422
TI  - A density functional theory study of the benzene-water complex.
AB  - The intermolecular interaction of the benzene-water complex is calculated using
      real-space pseudopotential density functional theory utilizing a van der Waals
      density functional. Our results for the intermolecular potential energy surface
      clearly show a stable configuration with the water molecule standing above or
      below the benzene with one or both of the H atoms pointing toward the benzene
      plane, as predicted by previous studies. However, when the water molecule is
      pulled outside the perimeter of the ring, the configuration of the complex
      becomes unstable, with the water molecule attaching in a saddle point
      configuration to the rim of the benzene with its O atom adjacent to a benzene H.
      We find that this structural change is connected to a change in interaction from
      H (water)/pi cloud (benzene) to O (water)/H (benzene). We compare our results for
      the ground-state structure with results from experiments and quantum-chemical
      calculations.

PMID- 18729423
TI  - Electroabsorption spectra of quadrupolar and octupolar dyes in solution: beyond
      the liptay formulation.
AB  - We present theoretical models for electroabsorption (EA) spectra of polar and
      multipolar (quadrupolar and octupolar) organic chromophores in solutions. Based
      on essential-state models for the electronic structure, we obtain closed
      expressions for the EA spectra of these dyes. For polar dyes, we regain the well
      known Liptay result, which relates the EA spectrum to the linear absorption
      spectrum and its first and second derivatives. For multipolar dyes, an additional
      contribution is found, which is due to the field-induced absorption toward dark
      states: when the dark states are close in energy to allowed states, this term
      leads to spurious second-derivative-like structures in the EA spectrum. This is
      particularly well-apparent for quadrupolar dyes where second-derivative
      contributions to the EA signal are symmetry-forbidden. The extension of essential
      state models to account for slow degrees of freedom, including molecular
      vibrations and polar solvation, leads to a more-realistic description of optical
      spectra but hinders the analytical treatment of EA. However, numerically exact EA
      spectra can be obtained along the same lines that have been recently developed
      for linear and two-photon absorption spectra of (multi)polar organic chromophores
      in solution. Essential-state models offer the possibility for a joint analysis of
      linear and nonlinear spectra (including EA) of (multi)polar dyes: reliable
      information can then be extracted also on molecular properties for systems where
      overlapping signals from allowed and dark states would hinder the standard
      analysis of EA spectra.

PMID- 18729424
TI  - Comparison of quantitative conformer analyses by nuclear magnetic resonance and
      Raman optical activity spectra for model dipeptides.
AB  - Interpretation of the Raman optical activity (ROA) of peptides is difficult
      because of molecular flexibility and interaction with the solvent. Typically,
      simulations and experiments are compared in terms of a qualitative agreement
      between the spectra. However, on a series of the Pro-Gly, Gly-Pro, Pro-Ala, and
      Ala-Pro dipeptides more precise conformer ratios could be obtained with the aid
      of the density functional computations and numerical decomposition of the
      spectral shapes. All observed transitions were assigned, and the computed
      transition frequencies were scaled accordingly. Then the populations predicted by
      the optical spectroscopy agreed within a few percent with an analysis of the spin
      spin coupling constants based on the Karplus equations, which was confirmed also
      by a comparison of calculated and experimental NMR couplings. The results are
      supported by molecular dynamics simulations and related to the previous
      conformational studies of similar molecules.

PMID- 18729425
TI  - Noble-gas-induced disproportionation reactions: facile superoxo-to-peroxo
      conversion on chromium dioxide.
AB  - Laser-evaporated chromium atoms are shown to insert into dioxygen to form CrO 2
      in solid argon. Annealing allows diffusion and reactions to form (eta (2)-O 2)
      2CrO 2, which is characterized as [(O 2 (-)) 2(CrO 2) (2+)], a side-on bonded
      disuperoxo-chromium dioxide complex. The (eta (2)-O 2) 2CrO 2 complex further
      reacts with xenon atom doped in solid argon to give (eta (1)-OO)(eta (2)-O 2)CrO
      2(Xe), which can be regarded as an O 2 molecule weakly interacting with [(O 2) (2
      )(CrO 2) (2+)Xe], a side-on bonded peroxo-chromium dioxide-xenon complex. The
      results indicate surprisingly that xenon atom induces a disproportionation
      reaction from superoxo to peroxo and dioxygen complex.

PMID- 18729426
TI  - Theoretical characterization of a typical hole/exciton-blocking material
      bathocuproine and its analogues.
AB  - The structural, electronic, and carrier transport properties of bathocuproine
      (BCP), which is a typical hole/exciton-blocking material applied in organic light
      emitting diodes (OLEDs), have been investigated based on density functional
      theory (DFT) and ab initio HF method. The detail characterizations of frontier
      electronic structure and lowest-energy optical transitions have been studied by
      means of time-dependent density functional theory (TD-DFT). Five BCP analogues, o
      phenanthroline (1), 2,9-dimethyl-1,10-phenanthroline (2), 2,9-diphenyl-1,10
      phenanthroline (3), 4,7-diphenyl-1,10-phenanthroline (4), and 2,9
      bis(trifluoromethyl)-1,10-phenanthroline (5) have also been studied in order to
      select more suitable candidates of efficient hole-blocking materials. The
      calculated results showed that rigid planar structures, conjugate degrees, and
      substitute groups play crucial roles in the hole/exciton-blocking and electron
      transport properties of these materials. The calculated geometries, ionization
      energies (IP), and energy gap between the singlet ground state and triplet
      excited state (E(T1)) were well in agreement with the experimental results. On
      the basis of the incoherent transport model, the calculated electron mobility of
      BCP is 1.79 x 10(-2) cm(2)/(V s), which is comparable to experimental results of
      1.1 x 10(-3) cm(2)/(V s). The electron mobilities for compounds 1, 4, and 5 are
      3.45 x 10(-2), 2.90 x 10(-2), and 1.40 x 10(-2) cm(2)/(V s), respectively. The
      calculated results indicated that compounds 1, 4, and 5 may be more effective
      hole/exciton-blocking materials than BCP.

PMID- 18729427
TI  - Hindered rotation of the silyl group in liquid-phase NMR spectra of 9
      silyltriptycene derivatives: a comparison with the methyl analogues.
AB  - Three 9-silyltriptycene derivatives, 1,4-dichloro- (DCST), 1,4-dibromo- (DBST),
      and 1,4-dimethyl-9-silyltriptycene (DMST) were synthesized, and temperature
      variable (1)H NMR spectra thereof were measured. Below 220 K for DMST, and below
      250 K for DCST and DBST, rotation of the silyl group becomes practically frozen
      on the NMR time scale. Iterative line shape analysis of the silyl proton spectra
      reveals that the familiar Alexander-Binsch line shape equation, employing only
      one rate constant for the observed rate process, is adequate in these cases. This
      is at a striking variance with the behavior of the methyl group in the analogous
      compounds, investigated by us recently, where fingerprints of the damped quantum
      rotation effect, a phenomenon once predicted by us, are clearly visible in the
      experimental spectra of the methyl protons. In the damped rotation approach, the
      relevant dynamics are described in terms of two quantum rate processes
      characterized by two coherence-damping constants, and the Alexander-Binsch model
      is obtained as a limiting case where these two constants become equal. The
      possible reasons of the differences between the dynamics of the silyl and methyl
      groups in the same molecular environment are discussed.

PMID- 18729429
TI  - Electronic spectra of the MgC4H and MgC6H radicals.
AB  - Electronic transitions of the linear MgC 4H and MgC 6H radicals have been
      observed in the gas phase using laser-induced fluorescence spectroscopy. The
      species were prepared in a supersonic expansion by ablation of a magnesium rod in
      the presence of acetylene, diacetylene, or methane gas. The transitions were
      recorded in the 445-446 nm region and assigned to the A (2)Pi- X (2)Sigma (+)
      systems ( T 0 = 22 431.978(7) and 22 090.08(7) cm (-1)) based on previously
      reported mass-selective resonance-enhanced ionization spectra and the rotational
      structure. A spectral fit in MgC 4H yields the rotational constants B'' =
      0.04619(19) cm (-1) for the X (2)Sigma (+) state and B' = 0.04748(20) cm (-1) for
      A (2)Pi. Astrophysical implications are briefly addressed.

PMID- 18729428
TI  - Kinetics of the reaction between nitroxide and thiyl radicals: nitroxides as
      antioxidants in the presence of thiols.
AB  - Cyclic nitroxides effectively protect cells, tissues, isolated organs, and
      laboratory animals from radical-induced damage. The present study focuses on the
      kinetics and mechanisms of the reactions of piperidine and pyrrolidine nitroxides
      with thiyl radicals, which are involved in free radical "repair" equilibria, but
      being strong oxidants can also produce cell damage. Thiyl radicals derived from
      glutathione, cysteine, and penicillamine were generated in water by pulse
      radiolysis, and the rate constants of their reactions with 2,2,6,6
      tetramethylpiperidine-1-oxyl (TPO), 4-OH-TPO, and 3-carbamoyl-proxyl were
      determined to be (5-7) x 10 (8) M (-1) s (-1) at pH 5-7, independent of the
      structure of the nitroxide and the thiyl radical. It is suggested that the
      reaction of nitroxide (>NO (*)) with thiyl radical (RS (*)) yields an unstable
      adduct (>NOSR). The deprotonated form of this adduct decomposes via heterolysis
      of the N-O bond, yielding the respective amine (>NH) and sulfinic acid (RS(O)OH).
      The protonated form of the adduct decomposes via homolysis of the N-O bond,
      forming the aminium radical (>NH (*+)) and sulfinyl radical (RSO (*)), which by
      subsequent reactions involving thiol and nitroxide produce the respective amine
      and sulfonic acid (RS(O) 2OH). Nitroxides that are oxidized to the respective
      oxoammonium cations (>N (+)O) are recovered in the presence of NADH but not in
      the presence of thiols. This suggests that the reaction of >N (+)O with thiols
      yields the respective amine. Two alternative mechanisms are suggested, where >N
      (+)O reacts with thiolate (RS (-)) directly generating the adduct >NOSR or
      indirectly forming >NO (*) and RS (*), which subsequently together yield the
      adduct >NOSR. Under physiological conditions the adduct is mainly deprotonated,
      and therefore nitroxides can detoxify thiyl radicals. The proposed mechanism can
      account for the protective effect of nitroxides against reactive oxygen- and
      nitrogen-derived species in the presence of thiols.

PMID- 18729430
TI  - Limits of the plane wave approximation in the measurement of molecular
      properties.
AB  - Rescattering electrons offer great potential as probes of molecular properties on
      ultrafast timescales. The most famous example is molecular tomography, in which
      high harmonic spectra of oriented molecules are mapped to "tomographic images" of
      the relevant molecular orbitals. The accuracy of such reconstructions can be
      greatly affected by the distortion of scattering wave functions from their
      asymptotic forms due to interactions with the parent ion. We investigate the
      validity of the commonly used plane wave approximation in molecular tomography,
      showing how such distortions affect the resulting orbital reconstructions.

PMID- 18729431
TI  - Direct observation of photoinduced bent nitrosyl excited-state complexes.
AB  - Ground-state structures with side-on nitrosyl (eta (2)-NO) and isonitrosyl (ON)
      ligands have been observed in a variety of transition-metal complexes. In
      contrast, excited-state structures with bent-NO ligands have been proposed for
      years but never directly observed. Here, we use picosecond time-resolved infrared
      spectroscopy and density functional theory (DFT) modeling to study the
      photochemistry of Co(CO) 3(NO), a model transition-metal-NO compound.
      Surprisingly, we have observed no evidence for ON and eta (2)-NO structural
      isomers, but we have observed two bent-NO complexes. DFT modeling of the ground-
      and excited-state potentials indicates that the bent-NO complexes correspond to
      triplet excited states. Photolysis of Co(CO) 3(NO) with a 400-nm pump pulse leads
      to population of a manifold of excited states which decay to form an excited
      state triplet bent-NO complex within 1 ps. This structure relaxes to the ground
      triplet state in ca. 350 ps to form a second bent-NO structure.

PMID- 18729432
TI  - The effect of NaOH on the liquid-phase hydrodechlorination of dioxins over
      Pd/gamma-Al2O3.
AB  - The effect of sodium hydroxide on the-liquid phase hydrodechlorination (LPHDC) of
      polychlorinated dibenzo- p-dioxins/polychlorinated dibenzofurans (PCDD/Fs) over
      2% Pd/gamma-Al 2O 3 was evaluated. Reactions were carried out using 2-propanol
      both as a hydrogen donor and as a solvent. Fresh and used catalyst samples were
      characterized by BET, hydrogen chemisorption, TEM/EDS, XPS, and TPR. When the
      reaction mixture contained no NaOH, active-phase leaching and Pd-C formation were
      observed even after 10 min of reaction. Therefore, sodium hydroxide appears to be
      required to maintain surface metal clusters on the support and avoid binding of
      carbon species to the active metal. On the other hand, excess NaOH in the
      reaction mixture led to deposition of organic and inorganic solid residues on the
      catalyst surface, blocking the active sites. Under the conditions of this study,
      the addition of 30 mg of NaOH maintained the basicity of the system and
      diminished deposition of solid residues on the catalyst samples, and almost 100%
      detoxification was reached after a 3 h reaction.

PMID- 18729433
TI  - UV absorption cross-sections of a series of dimethylbenzaldehydes.
AB  - The ultraviolet absorption cross-sections of 2,4-, 2,5-, 2,6-, 3,4- and 3,5-
      dimethylbenzaldehydes are reported in the wavelength range 240-320 nm. The
      measurements were carried out in the temperature range 318-363 K using two
      different experimental systems (D 2 lamp-monochromator and D 2 lamp-diode array).
      The absorption spectra of the five aldehydes have been found to exhibit
      relatively high absorption cross-sections in the region of the tropospheric
      interest with maxima around 290 nm. This work provides the first UV cross-section
      measurements for these aromatic aldehydes. The obtained cross-section values
      enable us to estimate the tropospheric photolysis lifetimes of these compounds.
      The results suggest that photolysis could be an important removal process for
      these species in the troposphere.

PMID- 18729434
TI  - Dynamics of weak and strong collisions: highly vibrationally excited pyrazine (E
      = 37900 cm(-1)) with DCl.
AB  - The outcome of energy transfer due to single collisions between highly
      vibrationally excited pyrazine (E = 37,900 cm(-1)) and DCl is measured for the
      appearance of individual low-J rotational states of DCl using high-resolution
      transient IR absorption. Appearance profiles from double-Gaussian transient
      lineshapes were measured for a number of DCl states with J = 2-12. These data
      give information on the recoil velocity distributions, appearance rates, and
      populations of individual states of the scattered molecules. These data
      complement previous studies on high-J state DCl scattering (Li, Z.; Korobkova,
      E.; Werner, K.; Shum, L.; Mullin, A. S. J. Chem. Phys. 2005, 123, 174306), and
      together, they provide a full description of the V-RT collisions with DCl that
      quench pyrazine(E). Scattered DCl (v = 0) molecules with J = 2-21 are
      rotationally hot with T(rot) = 880 +/- 100 K. Center-of-mass translational energy
      distributions are T(rel) approximately 700 K for J < 15. Broader velocity
      distributions are observed for the J = 15-20 states. The rate constant for V-RT
      energy transfer is 4.6 x 10(-10) cm(3) molecule(-1) s(-1). This value is a lower
      limit to the overall rate constant for energy transfer and corresponds to
      approximately 85% of the Lennard-Jones collision rate. We estimate scattering
      into the DCl (v = 1) state occurs in approximately 1% of collisions. The energy
      transfer probability distribution P(DeltaE) is presented and yields DeltaE = 888
      cm(-1).

PMID- 18729435
TI  - Overtone dissociation of peroxynitric acid (HO2NO2): absorption cross sections
      and photolysis products.
AB  - Band strengths for the second (3nuOH) and third (4nuOH) overtones of the OH
      stretch vibration of peroxynitric acid, HO2NO2 (PNA) in the gas-phase were
      measured using Cavity Ring-Down Spectroscopy (CRDS). Both OH overtone transitions
      show diffuse smoothly varying symmetrical absorption profiles without observable
      rotational structure. Integrated band strengths (base e) at 296 K were determined
      to be S(3nuOH) = (5.7 +/- 1.1) x 10(-20) and S(4nuOH) = (4.9 +/- 0.9) x 10(-21)
      cm(2) molecule(-1) cm(-1) with peak cross sections of (8.8 +/- 1.7) x 10(-22) and
      (7.0 +/- 1.3) x 10(-23) cm(2) molecule(-1) at 10086.0 +/- 0.2 cm(-1) and 13095.8
      +/- 0.4 cm(-1), respectively, using PNA concentrations measured on line by
      Fourier-transform infrared and ultraviolet absorption spectroscopy. The quoted
      uncertainties are 2sigma (95% confidence level) and include estimated systematic
      errors in the measurements. OH overtone spectra measured at lower temperature,
      231 K, showed a narrowing of the 3nuOH band along with an increase in its peak
      absorption cross section, but no change in S(3nuOH) to within the precision of
      the measurement (+/-9%). Measurement of a PNA action spectrum showed that HO2 is
      produced from second overtone photodissociation. The action spectrum agreed with
      the CRDS absorption spectra. The PNA cross sections determined in this work for
      3nuOH and 4nuOH will increase calculated atmospheric photolysis rates of PNA
      slightly.

PMID- 18729436
TI  - Polarizable continuum model study on the solvent effect of polymer matrix in
      poly(ethylene oxide)-based solid electrolyte.
AB  - The Polarizable Continuum Model has been used to study the effect of polymer
      matrix on Li (+) and Mg (2+) complexation in poly(ethylene oxide)-based solid
      electrolyte. Structures of complexes, stabilization energies, and vibrational
      frequencies are compared with corresponding vacuum values. The solvent effect of
      the polymer decreases with increasing cation coordination number. Optimized
      complex geometries do not differ significantly compared to vacuum calculations.
      Calculated shifts in vibrational frequencies depend on the complex structure; for
      hexacoordinated ion most frequencies are slightly red-shifted. The most important
      effect is the decrease of differences between relative stabilities of different
      structures in the solvent.

PMID- 18729437
TI  - Anion-anion assembly in crystal of sodium nitroprusside.
AB  - The experimental charge density in the crystal of disodium
      pentacyanonitrosoferrate (sodium nitroprusside) dihydrate was analyzed in detail
      by means of Bader's atoms in molecules theory. It was shown that nitroprusside
      anion is involved in relatively strong self-interactions through the nitroso
      group. The obtained results agree well with the spectroscopic data, indicating
      the tendency of the corresponding moiety to the formation of anion-anion
      association both in solutions and in the crystalline phase.

PMID- 18729438
TI  - Solvation effects on the intracluster elimination channels in M+(L)n, where M+=
      Mg+ and Ca+, L = CH3OH, and NH3, and n = 2-6.
AB  - The methanol and ammonia solvated Ca (+) or Mg (+) clusters are known to go
      through intracluster H or CH 3 eliminations which are typically switched on just
      below n = 6. By first principles calculations at the B3LYP/6-311+G** level, we
      have identified the transition structures, activation barriers, and energy
      changes in these reactions for clusters with 2-6 solvent molecules. The
      activation barrier is crucial to explain the previously reported experimental
      results. While increasing number of solvent molecules stabilizes a transition
      structure, the increasing presence of solvent molecules in the first solvation
      shell makes it difficult for the metal ion to assist the bond breaking through
      its interaction with the departing H atom or CH 3 group. The balance of these two
      factors determines whether a particular elimination channel could be switched on.

PMID- 18729439
TI  - The binding behavior of cyclodextrins toward a nitroxide spin probe in the
      presence of different alcohols as studied by EPR.
AB  - Stability constants, rates of association and dissociation, and thermodynamic and
      activation parameters for the formation of inclusion complexes between the
      radical guest, N-benzyl- tert-butyl- d 9-nitroxide and beta- or 2,6- O-dimethyl
      beta-cyclodextrin (CDs), have been determined by EPR spectroscopy in water in the
      presence of 14 different alcohols, differing in size and lipophilicity. In all
      cases, it was found that addition of alcohol, depending on its structure and
      concentration, causes a reduction of the stability of the paramagnetic complex.
      Global analysis of EPR data allowed us to explain the CDs binding behavior: we
      discarded the formation of a ternary complex, where alcohol and radical guest are
      coincluded into CD cavity, while data were found more consistent with the
      formation of a binary complex alcohol:CD competing with the monitored complex
      nitroxide:CD. Both kinetic and thermodynamic analysis of the experimental results
      have revealed that the presence of alcohols affects to a larger extent the
      dissociation rather then the association of radical probe and CD and that the
      former process is of greater importance in determining the stability of the
      complex, this confirming the reliability of the competition model proposed. This
      competition has been used for the indirect determination of the stability
      constants of complexes between CD and examined alcohols. By using a similar
      approach, we showed EPR spectroscopy can be considered a rapid and accurate
      technique to investigate the CDs binding behavior toward different nonradical
      guest.

PMID- 18729440
TI  - Theoretical study on the intracluster elimination channels for Mg+(CH3OH),
      Ca+(CH3OH), Mg+(NH3), and Ca+(NH3).
AB  - The intracluster elimination reactions in solvated alkaline earth metal
      monocation clusters, M (+)L n , are known to be size-dependent, indicating links
      between chemical reactivity and the solvation environment controlled by the
      cluster size. For the methanol and ammonia clusters, there are a number of
      competing elimination channels involving the breaking of O-H, C-H, O-CH 3, or N-H
      bond. In this report, we focus on the four clusters with only one solvent
      molecule and systematically map out the reaction paths and intermediates. The
      interaction between the metal ion and the departing H atom or CH 3 group varies
      considerably, depending on the interaction between the metal ion and the
      remaining group. The understanding of the nature of these interactions and the
      evaluation of various theoretical levels in treating these reactions provide a
      solid base for the investigation of the solvation effects on the chemical
      reactivity of the larger clusters.

PMID- 18729441
TI  - Modeling photoabsorption of the asFP595 chromophore.
AB  - The fluorescent protein asFP595 is a promising photoswitchable biomarker for
      studying processes in living cells. We present the results of a high level
      theoretical study of photoabsorption properties of the model asFP595 chromophore
      molecule in biologically relevant protonation states: anionic, zwitterionic, and
      neutral. Ground state equilibrium geometry parameters are optimized in the
      PBE0/(aug)-cc-pVDZ density functional theory approximation. An augmented version
      of multiconfigurational quasidegenerate perturbation theory (aug-MCQDPT2)
      following the state-averaged CASSCF/(aug)-cc-pVDZ calculations is used to
      estimate the vertical S0-S1 excitation energies for all chromophore species. An
      accuracy of this approach is validated by comparing the computed estimates of the
      S0-S1 absorption maximum of the closely related chromophore from the DsRed
      protein to the known experimental value in the gas phase. An influence of the
      CASSCF active space on the aug-MCQDPT2 excitation energies is analyzed. The
      zwitterionic form of the asFP595 chromophore is found to be the most sensitive to
      a particular choice and amount of active orbitals. This observation is explained
      by the charge-transfer type of the S0-S1 transition involving the entire
      conjugated pi-electron system for the zwitterionic protonation state. According
      to the calculation results, the anionic form in the trans conformation is found
      to possess the most red-shifted absorption band with the maximum located at 543
      nm. The bands of the zwitterionic and neutral forms are considerably blue-shifted
      compared to those of the anionic form. These conclusions are at variance with the
      results obtained in the TDDFT approximation for the asFP595 chromophore. The
      absorption wavelengths computed in the aug-MCQDPT2/CASSCF theory are as follows:
      543 (535), 470 (476), and 415 (417) nm for the anionic, zwitterionic, and neutral
      forms of the trans and cis (in parentheses) isomers of the asFP595 chromophore.
      These data can be used as a reference for further theoretical studies of the
      asFP595 chromophore in different media and for modeling photoabsorption
      properties of the asFP595 fluorescent protein.

PMID- 18729442
TI  - Enhanced intersystem crossing via a high energy charge transfer state in a
      perylenediimide-perylenemonoimide dyad.
AB  - The electronic relaxation processes of a photoexcited linear perylenediimide
      perylenemonoimide (PDI-PMI) acceptor-donor dyad were studied. PDI-PMI serves as a
      model compound for donor-acceptor systems in photovoltaic devices and has been
      designed to have a high-energy PDI (-*)-PMI (+*) charge transfer (CT) state. Our
      study focuses on the minimal Gibbs free energy (Delta G ET) required to achieve
      quantitative CT and on establishing the role of charge recombination to a triplet
      state. We used time-resolved photoluminescence and picosecond photoinduced
      absorption (PIA) to investigate excited singlet (S 1) and CT states and
      complemented these experiments with singlet oxygen ( (1)Delta g) luminescence and
      PIA measurements on longer timescales to study the population of triplet excited
      states (T 1). In an apolar solvent like cyclohexene (CHX), photoinduced electron
      transfer does not occur, but in more polar solvents such as toluene (TOL) and
      chlorobenzene (CB), photoexcitation is followed by a fast electron transfer,
      populating the PDI (-*)-PMI (+*) CT state. We extract rate constants for electron
      transfer (ET; S 1-->CT), back electron transfer (BET; S 1<--CT), and charge
      recombination (CR) to lower-energy states (CT-->S 0 and CT-->T 1). Temperature
      dependent measurements yield the barriers for the transfer reactions. For ET and
      BET, these correspond to predictions from Marcus-Jortner theory and show that
      efficient, near quantitative electron transfer ( k ET/ k BET >or= 100) can be
      obtained when Delta G ET approximately -120 meV. With respect to triplet state
      formation, we find a relatively low triplet quantum yield (Phi T < 25%) in CHX
      but much higher values (Phi T = 30-98%) in TOL and CB. We identify the PDI (-*)
      PMI (+*) state as a precursor to the T 1 state. Recombination to T 1, rather than
      to the ground-state S 0, is required to rationalize the experimental barrier for
      CR. Finally, we discuss the relevance of these results for electron donor
      acceptor films in photovoltaic devices.

PMID- 18729443
TI  - Electrogenerated chemiluminescence of 9,10-diphenylanthracene, rubrene, and
      anthracene in fluorinated aromatic solvents.
AB  - The electrogenerated chemiluminescence (ECL) of 9,10-diphenylanthracene (DPA),
      rubrene, and anthracene has been studied in fluorinated aromatic solvents. Mixed
      annihilation ECL between aromatic luminophores and quinones was observed in
      solvent systems containing acetonitrile and either benzene, benzotrifluoride, 3
      fluorobenzotrifluoride, or 1,3-bis(trifluoromethyl)benzene. Increases in ECL
      efficiency (phi ecl, photons generated per redox event) correlated with
      decreasing solvent polarity when 1,4-benzoquinone was used as a nonemitting ECL
      partner. However, opposite results were observed using 1,4-naphthaoquinone (NQ)
      as a nonemitting partner. phi ecl also correlated with radical anion stability of
      NQ in these solvent systems, as indicated by reverse/forward current ratios ( I
      r/ I f), suggesting noncovalent interactions between the solvent and the
      nonemitting ECL partner. Specifically, the reaction of an aromatic luminophore
      with 1,4-naphthoquinone in acetonitrile/benzotrifluoride showed a 1.03-1.63-fold
      increases in ECL efficiency over that of acetonitrile/benzene. Slight blue shifts
      ( approximately 3 nm) in photoluminescence and ECL emissions were seen as solvent
      polarity increased. Reaction enthalpies of each system were estimated using half
      wave potentials of oxidation and reduction and were found to correlate well with
      emission energy.

PMID- 18729445
TI  - 3,4-Dihydro-2H-1,4-benzoxazine derivatives combining thrombin inhibitory and
      glycoprotein IIb/IIIa receptor antagonistic activity as a novel class of
      antithrombotic compounds with dual function.
AB  - 3,4-Dihydro-2 H-1,4-benzoxazine derivatives possessing both thrombin inhibitory
      and glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonistic activities were
      obtained by combining mimetics of the d-Phe-Pro-Arg pharmacophore of thrombin
      inhibitors and the Arg-Gly-Asp pharmacophore of GPIIb/IIIa receptor antagonists
      in the same low molecular weight peptidomimetic compound. Systematic variation of
      the position of substituents around the 3,4-dihydro- 2H-1,4-benzoxazine nucleus,
      the distance between the carboxylate and amidine moieties, together with
      additional substituents to fill the thrombin S 2 and S 3 pockets resulted in
      compounds displaying submicromolar inhibition constants ( K i) for thrombin and
      submicromolar IC 50 for inhibition of binding of fibrinogen to platelet
      GPIIb/IIIa receptor. Some of these compounds, such as 17a, 17b, 17d, and 17h
      possessing a well balanced activity at both targets, are a good starting point
      for further optimization. Incorporation of anticoagulant and platelet
      antiaggregatory activity in the same molecule constitutes a promising approach
      toward novel antithrombotic agents.

PMID- 18729446
TI  - A new approach for the detection of ethylene using silica-supported palladium
      complexes.
AB  - The coordination of olefins to square-planar Pd(II) and Pt(II) complexes
      containing 2,9-dimethylphenanthroline ( L1) often involves a change of color
      associated with a change of geometry at the metal center. In order to obtain
      suitable colorimetric detectors for ethylene gas, a series of new Pd(II) and
      Pt(II) compounds with a range of 2,9-disubstituted phenanthroline ligands [2,9-di
      n-butyl-1,10-phenanthroline ( L2), 2,9-di- s-butyl-1,10-phenanthroline ( L3),
      2,9-diphenyl-1,10-phenanthroline ( L4), and 2,9-dimethyl-4,7-diphenyl-1,10
      phenanthroline (bathocuproine, L5)] have been prepared and their reactivity
      toward ethylene investigated both in solution and after depositing the detector
      compounds on a variety of solid supports. The Pd(II) complex [PdCl 2( L2)]
      supported on silica undergoes a clear color change upon exposure to ethylene,
      while remaining stable toward air and water, and forms the basis for new simple
      colorimetric detectors with potential applications in ethylene pipe-leak
      detection and the monitoring of fruit ripening. Encouragingly, the detector is
      able to discriminate between fruit at different stages of ripening. The response
      of the detector to other volatiles was also examined, and specific color changes
      were also observed upon exposure to aromatic acetylenes. The crystal structures
      of four new derivatives, including the ethylene-Pt(II) complex [PtCl 2(C 2H 4)(
      L2)], are also described.

PMID- 18729444
TI  - Residues in the 11 A channel of histone deacetylase 1 promote catalytic activity:
      implications for designing isoform-selective histone deacetylase inhibitors.
AB  - Histone deacetylase 1 (HDAC1) has been linked to cell growth and cell cycle
      regulation, which makes it a widely recognized target for anticancer drugs.
      Whereas variations of the metal-binding and capping groups of HDAC inhibitors
      have been studied extensively, the role of the linker region is less well known,
      despite the potency of inhibitors with diverse linkers, such as MS-275. To
      facilitate a drug design that targets HDAC1, we assessed the influence of
      residues in the 11 A channel of the HDAC1 active site on activity by using an
      alanine scan. The mutation of eight channel residues to alanine resulted in a
      substantial reduction in deacetylase activity. Molecular dynamics simulations
      indicated that alanine mutation results in significant movement of the active
      site channel, which suggests that channel residues promote HDAC1 activity by
      influencing substrate interactions. With little characterization of HDAC1
      available, the combined experimental and computational results define the active
      site residues of HDAC1 that are critical for substrate/inhibitor binding and
      provide important insight into drug design.

PMID- 18729447
TI  - Synthesis, structure, and spectroscopic properties of chiral oxorhenium(V)
      complexes incorporating polydentate ligands derived from L-amino acids: a density
      functional theory/time-dependent density functional theory investigation.
AB  - The oxorhenium(V) complexes [Re (V)O(L A)Cl 2] bearing the (N-2-pyridylmethyl) of
      l-valine (HL A (1)), l-leucine (HL A (2)), and l-phenylalanine (HL A (3)) and [Re
      (V)O(L B)Cl] containing the {(N-2pyridylmethyl)-(N-(5-nitro-2-hydroxybenzyl)} of
      l-valine (H 2L B (1)), l-leucine (H 2L B (2)), and l-phenylalanine (H 2L B (3))
      are presented in this article. The complexes are isolated in enantiomeric pure
      form examined from X-ray structure determination. The complexes are characterized
      by spectroscopic and electrochemical methods. The molecular structures observed
      in the solid state are grossly preserved in solution ( (1)H, (13)C, and circular
      dichroism spectra). Gas-phase geometry optimization and the electronic structures
      of [Re (V)O(L A (1))Cl 2], [Re (V)O(L A (2))Cl 2], and [Re (V)O(L B (2))Cl] have
      been investigated with the framework of density functional theory. The absorption
      and circular dichroism spectra of the complexes were also calculated applying
      time-dependent density functional theory (TDDFT) using the conductor-like
      polarizable continuum solvent model to understand the origin of the electronic
      excitations. The chemical shift ( (1)H and (13)C) as well as (1)H- (1)H spin-spin
      coupling constant were also computed by the gauge-independent atomic orbital
      method, and the computed values are consistent with the experimental data.

PMID- 18729448
TI  - Magneto-structure relationship in copper(II) and nickel(II) complexes chelated
      with stable tert-butyl 5-phenyl-2-pyridyl nitroxide and related radicals.
AB  - We have isolated and characterized a new paramagnetic bidentate ligand, tert
      butyl 5-phenyl-2-pyridyl nitroxide (phpyNO). The spin distribution onto the
      pyridine ring was clarified from the Electron Spin Resonance spectrum.
      Complexation of phpyNO with nickel(II) and copper(II) ions gave ML 2-type
      chelated compounds. The magnetic measurements of [Ni(phpyNO) 2(H 2O) 2].(ClO 4) 2
      and [Cu(phpyNO) 2(H 2O)].(ClO 4) 2.C 6H 4Cl 2 revealed that the metal-radical
      exchange couplings were ferromagnetic with 2 J/ k B = +409(10) and +434(12) K,
      respectively. The torsion angle (varphi) around M-O-N-C 2py can be regarded as a
      reliable indicator for the plane geometry of chelates; namely, highly planar
      chelates defined by small varphi exhibit ferromagnetic coupling. An approximate
      linear relation was found in the J versus varphi plot using the data of the
      present complexes and related known compounds. The critical angle of varphi, at
      which the sign of the metal-radical exchange changes from positive to negative,
      was 12.6(9) degrees . This finding could be almost reproduced by density
      functional theory calculation on a model copper(II)-nitroxide dyad. The exchange
      couplings in equatorially coordinated copper(II)- and nickel(II)-nitroxide
      complexes are very strongly ferromagnetic by nature.

PMID- 18729449
TI  - Highly fluorescent group 13 metal complexes with cyclic, aromatic hydroxamic acid
      ligands.
AB  - The neutral complexes of two ligands based on the 1-oxo-2-hydroxy-isoquinoline
      motif with group 13 metals (Al, Ga, In) show bright blue-violet luminescence in
      organic solvents. The corresponding transition can be attributed to ligand
      centered singlet emission, characterized by a small Stokes shifts of only a few
      nanometers combined with lifetimes in the range between 1 and 3 ns. The
      fluorescence efficiency is high, with quantum yields of up to 37% in benzene
      solution. The crystal structure of one of the indium(III) complexes (trigonal
      space group R3, a = b = 13.0384(15) A, c = 32.870(8) A, alpha = beta = 90 degrees
      , gamma = 120 degrees , V = 4839.3(14) A (3), Z = 6) shows a six-coordinate
      geometry around the indium center, which is close to trigonal-prismatic, with a
      twist angle between the two trigonal faces of 20.7 degrees . Time-dependent
      density functional theory calculations (Al and Ga, B3LYP/6-31G(d); In,
      B3LYP/LANL2DZ) of the fac and mer isomers with one of the two ligands indicate
      that there is no clear preference for either one of the isomeric forms of the
      metal complexes. In addition, the metal centers do not have a significant
      influence on the electronic structure nor, as a consequence, on the predominant
      intraligand optical transitions.

PMID- 18729450
TI  - Cyclic ruthenium-alkylidene catalysts for ring-expansion metathesis
      polymerization.
AB  - A series of cyclic Ru-alkylidene catalysts have been prepared and evaluated for
      their efficiency in ring-expansion metathesis polymerization (REMP). The catalyst
      structures feature chelating tethers extending from one N-atom of an N
      heterocyclic carbene (NHC) ligand to the Ru metal center. The catalyst design is
      modular in nature, which provided access to Ru complexes having varying tether
      lengths, as well as electronically different NHC ligands. Structural impacts of
      the tether length were unveiled through (1)H NMR spectroscopy as well as single
      crystal X-ray analyses. Catalyst activities were evaluated via polymerization of
      cyclooctene, and key data are provided regarding propagation rates,
      intramolecular chain transfer, and catalyst stabilities, three areas necessary
      for the efficient synthesis of cyclic poly(olefin)s via REMP. From these studies,
      it was determined that while increasing the tether length of the catalyst leads
      to enhanced rates of polymerization, shorter tethers were found to facilitate
      intramolecular chain transfer and release of catalyst from the polymer.
      Electronic modification of the NHC via backbone saturation was found to enhance
      polymerization rates to a greater extent than did homologation of the tether.
      Overall, cyclic Ru complexes bearing 5- or 6-carbon tethers and saturated NHC
      ligands were found to be readily synthesized, bench-stable, and highly active
      catalysts for REMP.

PMID- 18729451
TI  - Prediction of the conditions for breathing of metal organic framework materials
      using a combination of X-ray powder diffraction, microcalorimetry, and molecular
      simulation.
AB  - The adsorption of C1 to C4 linear hydrocarbons in the flexible metal organic
      framework MIL-53(Cr) has been followed by adsorption manometry coupled with
      microcalorimetry and Synchrotron X-ray powder diffraction. This experimental
      investigation was completed by molecular modeling. In the case of methane, the
      solid remains rigid whatever the adsorbate amount. However for the C2-C4 series,
      an increasing flexibility of the structure is observed, which is ascribed first
      to a breathing of the material from a large pore to a narrow pore form followed
      by a further expansion at high pressure. The collected thermodynamic and
      structural information suggests that a minimum adsorption enthalpy of ca. 20 kJ
      mol (-1) in the initial large pore structure of MIL-53(Cr) is required to induce
      the structural transition "large to narrow pore". Further, the enthalpy of
      adsorption can be used to predict the pressure at which the structure reopens.
      Finally, the magnitude of the breathing can be related to the size of the probe
      molecule via the van der Waals volume. The above trends have been successfully
      verified in the case of water and carbon dioxide. This combined experimental and
      theoretical approach gives the first elements for the prediction of whether or
      not the MIL53 and similar flexible structures will respond to gas loading and
      what would be the pressure required and further the amplitude of the induced
      breathing.

PMID- 18729452
TI  - Combinatorial chemoenzymatic synthesis and high-throughput screening of
      sialosides.
AB  - Although the vital roles of structures containing sialic acid in biomolecular
      recognition are well documented, limited information is available on how sialic
      acid structural modifications, sialyl linkages, and the underlying glycan
      structures affect the binding or the activity of sialic acid-recognizing proteins
      and related downstream biological processes. A novel combinatorial chemoenzymatic
      method has been developed for the highly efficient synthesis of biotinylated
      sialosides containing different sialic acid structures and different underlying
      glycans in 96-well plates from biotinylated sialyltransferase acceptors and
      sialic acid precursors. By transferring the reaction mixtures to NeutrAvidin
      coated plates and assaying for the yields of enzymatic reactions using lectins
      recognizing sialyltransferase acceptors but not the sialylated products, the
      biotinylated sialoside products can be directly used, without purification, for
      high-throughput screening to quickly identify the ligand specificity of sialic
      acid-binding proteins. For a proof-of-principle experiment, 72 biotinylated
      alpha2,6-linked sialosides were synthesized in 96-well plates from 4 biotinylated
      sialyltransferase acceptors and 18 sialic acid precursors using a one-pot three
      enzyme system. High-throughput screening assays performed in NeutrAvidin-coated
      microtiter plates show that whereas Sambucus nigra Lectin binds to alpha2,6
      linked sialosides with high promiscuity, human Siglec-2 (CD22) is highly
      selective for a number of sialic acid structures and the underlying glycans in
      its sialoside ligands.

PMID- 18729453
TI  - Antioxidant capacity of seed coat, dehulled bean, and whole black soybeans in
      relation to their distributions of total phenolics, phenolic acids, anthocyanins,
      and isoflavones.
AB  - Black soybeans have been used as an excellent dietary source for disease
      prevention and health promotion in China for hundreds of years. However,
      information about the distribution of health-promoting phenolic compositions in
      different physical parts of black soybean and the contribution of phenolic
      compositions to overall antioxidant capacity is limited. To elucidate the
      distribution of phenolic composition and their contribution to antioxidant
      activities in black soybean, the total and individual phenolic profiles, and
      antioxidant capacities of seed coat, dehulled and whole black soybean were
      systematically investigated. The seed coat exhibited much higher total phenolic
      indexes and antioxidant activities than whole and dehulled black soybean.
      Dehulled black soybean possessed similar levels of total phenolic content, total
      flavonoid content, 2-diphenyl-1-picryhydrazyl (DPPH) radical scavenging activity,
      ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity
      (ORAC) activities as compared to whole yellow soybean. Cyanidin-3-glucoside,
      petunidin-3-glucoside, and peonidin-3-glucoside were detected in the seed coat
      but not in dehulled black soybean and yellow soybean. Among benzoic acid
      detected, caffeic and chlorogenic acid were the predominant phenolic acids. Whole
      black soybean and dehulled black soybean exhibited similar isoflavone contents in
      7- O-beta-glucosides and malonylglucosides of daidzein and genistein. The seed
      coat possessed significantly ( p < 0.05) lower 7- O-beta-glucosides and
      malonylglucosides of daidzein and genistein, acetylglycitin, and total
      isoflavones than whole and dehulled black soybean. The contribution of phenolics
      in the seed coat to the antioxidant activity of black soybean parts depends on
      the assay methods. When measured with the DPPH and FRAP methods, the seed coat
      contributed 90% of the total antioxidant capacity of black soybean. However, when
      measured with the ORAC method, the seed coat and dehulled portion contributed
      approximately equally the total antioxidant capacity of black soybeans. The
      information generated from this study on the distribution and content of their
      active components is useful for the effective use of black soybeans as an
      ingredient for promoting health.

PMID- 18729454
TI  - Influence of food acidulants and antioxidant spices on the bioaccessibility of
      beta-carotene from selected vegetables.
AB  - Four common food acidulants--amchur, lime, tamarind, and kokum--and two
      antioxidant spices--turmeric and onion--were examined for their influence on the
      bioaccessibility of beta-carotene from two fleshy and two leafy vegetables.
      Amchur and lime generally enhanced the bioaccessibility of beta-carotene from
      these test vegetables in many instances. Such an improved bioaccessibility was
      evident in both raw and heat-processed vegetables. The effect of lime juice was
      generally more pronounced than that of amchur. Turmeric significantly enhanced
      the bioaccessibility of beta-carotene from all of the vegetables tested,
      especially when heat-processed. Onion enhanced the bioaccessibility of beta
      carotene from pressure-cooked carrot and amaranth leaf and from open-pan-boiled
      pumpkin and fenugreek leaf. Lime juice and the antioxidant spices turmeric and
      onion minimized the loss of beta-carotene during heat processing of the
      vegetables. In the case of antioxidant spices, improved bioaccessibility of beta
      carotene from heat-processed vegetables is attributable to their role in
      minimizing the loss of this provitamin. Lime juice, which enhanced the
      bioaccessibility of this provitamin from both raw and heat-processed vegetables,
      probably exerted this effect by some other mechanism in addition to minimizing
      the loss of beta-carotene. Thus, the presence of food acidulants (lime
      juice/amchur) and antioxidant spices (turmeric/onion) proved to be advantageous
      in the context of deriving maximum beta-carotene from the vegetable sources.

PMID- 18729455
TI  - Nectar Flavonol rhamnosides are floral markers of acacia (Robinia pseudacacia)
      honey.
AB  - With the objective of finding floral markers for the determination of the
      botanical origin of acacia (robinia) honey, the phytochemicals present in nectar
      collected from Robinia pseudacacia flowers were analyzed by high-performance
      liquid chromatography-tandem mass spectrometry. Eight flavonoid glycosides were
      detected and characterized as kaempferol combinations with rhamnose and hexose.
      Acacia honey produced in the same location where the nectar was collected
      contained nectar-derived kaempferol rhamnosides. This is the first time that
      flavonoid glycosides have been found as honey constituents. Differences in the
      stability of nectar flavonoids during honey elaboration and ripening in the hive
      were shown to be due to hydrolytic enzymatic activity and to oxidation probably
      related to hydrogen peroxide (glucose-oxidase) activity. Acacia honeys contained
      propolis-derived flavonoid aglycones (468-4348 microg/100 g) and hydroxycinnamic
      acid derivatives (281-3249 microg/100 g). In addition, nectar-derived kaempferol
      glycosides were detected in all of the acacia honey samples analyzed (100-800
      microg/100 g). These flavonoids were not detected in any of the different honey
      samples analyzed previously from different floral origins other than acacia.
      Finding flavonoid glycosides in honey related to floral origin is particularly
      relevant as it considerably enlarges the number of possible suitable markers to
      be used for the determination of the floral origin of honeys.

PMID- 18729456
TI  - Determination of glucosamine and N-acetyl glucosamine in fungal cell walls.
AB  - A new method was developed to determine glucosamine (GlcN) and N-acetyl
      glucosamine (GlcNAc) in materials containing chitin and chitosan, such as fungal
      cell walls. It is based on two steps of hydrolysis with (i) concentrated sulfuric
      acid at low temperature and (ii) dilute sulfuric acid at high temperature,
      followed by one-step degradation with nitrous acid. In this process, chitin and
      chitosan are converted into anhydromannose and acetic acid. Anhydromannose
      represents the sum of GlcN and GlcNAc, whereas acetic acid is a marker for GlcNAc
      only. The method showed recovery of 90.1% of chitin and 85.7-92.4% of chitosan
      from commercial preparations. Furthermore, alkali insoluble material (AIM) from
      biomass of three strains of zygomycetes, Rhizopus oryzae, Mucor indicus, and
      Rhizomucor pusillus, was analyzed by this method. The glucosamine contents of AIM
      from R. oryzae and M. indicus were almost constant (41.7 +/- 2.2% and 42.0 +/-
      1.7%, respectively), while in R. pusillus, it decreased from 40.0 to 30.0% during
      cultivation from 1 to 6 days. The GlcNAc content of AIM from R. oryzae and R.
      pusillus increased from 24.9 to 31.0% and from 36.3 to 50.8%, respectively, in 6
      days, while it remained almost constant during the cultivation of M. indicus
      (23.5 +/- 0.8%).

PMID- 18729457
TI  - Foam-stabilizing effects and cling formation patterns of iso-alpha-acids and
      reduced iso-alpha-acids in lager beer.
AB  - Foam-stabilizing properties and cling formation patterns of iso-alpha-acids and
      reduced iso-alpha-acids were investigated using an unhopped lager beer. Unhopped
      beer was dosed with iso-alpha-acid (Iso), rho-iso-alpha-acid (Rho), tetrahydro
      iso-alpha-acid (Tetra), and hexahydro-iso-alpha-acid (Hexa), separately, over a
      range of concentrations from 2 to 10 ppm. A uniform foam was created by Inpack
      2000 Flasher Head and was measured by a NIBEM Foam Stability Tester (NIBEM-TPH)
      followed by a NIBEM Cling Meter (NIBEM-CLM) to determine the relationship between
      the concentration and NIBEM-30 and the cling formation ability of each compound.
      The foam-stabilizing power was determined to be Tetra, Hexa, Iso, and Rho from
      the strongest to weakest. Linear regression models were created using the NIBEM
      TPH data set, and on the basis of 95% confidence intervals, the foam stability of
      Tetra or Hexa became significantly larger than that of Iso when 2.4 or 4.2 ppm of
      Tetra or Hexa was used as a replacement for Iso, respectively. Cling formation
      patterns could be categorized into three groups: "ring", "mesh", and "powdery".
      The control beer had the lowest foam stability and did not yield any foam cling.

PMID- 18729458
TI  - Comparison of biotransformation of inorganic selenium by Lactobacillus and
      Saccharomyces in lactic fermentation process of yogurt and kefir.
AB  - The aim of the present study was to characterize, quantify, and compare the
      different selenium species that are produced when lactic fermentation with two
      different types of microorganisms, bacteria (Lactobacillus) and yeast
      (Saccharomyces), take place to produce yogurt and kefir, respectively, and to
      study the transformation process of these species as a function of time. These
      two dairy products were chosen for the study because they are highly consumed in
      different cultures. Moreover, the microorganisms present in the fermentation
      processes are different. While the bacteria Lactobacillus is the one responsible
      for yogurt fermentation, a partnership between bacteria and the yeast
      Saccharomyces causes kefir fermentation. A comparative study has been carried out
      by fermenting Se(IV) enriched milk in the presence of both types of
      microorganisms, where the concentration range studied was from 0.5 to 20 microg g
      (-1). Enzymatic extraction enabled selenium speciation profiles, obtained by
      anionic exchange and ion-pairing reversed phase high performance liquid
      chromatography (IP-RP-HPLC) with inductively coupled plasma mass spectrometry
      (ICP-MS) detection. Scanning electron microscopy (SEM) applied to the enriched
      samples showed segregated Se (0), at added concentrations higher than 5 microg g
      (-1). The main Se species formed depended on the type of microorganism involved
      in the fermentation process, SeCys 2 and MeSeCys being the main species generated
      in yogurt and SeMet in kefir. The results obtained are different for both kinds
      of samples. Lactic fermentation for yogurt produced an increment in selenocystine
      (SeCys 2) and Se-methylselenocysteine (MeSeCys), while fermentation to produce
      kefir also incremented the selenomethionine (SeMet) concentration. The Se species
      are stable for at least 10 and 15 days for kefir and yogurt, respectively. After
      this period, selenocystine concentration decreased, and the concentration of Se
      methylselenocysteine was found to significantly increase.

PMID- 18729459
TI  - In vitro analysis of protection of the enzyme bile salt hydrolase against enteric
      conditions by whey protein-gum arabic microencapsulation.
AB  - The interest in efficient intestinal delivery of health-promoting substances is
      increasing. However, the delivery of vulnerable substances such as enzymes
      requires specific attention. The transit through the stomach, where the pH is
      very low, can be detrimental to the enzymatic activity of the protein to be
      delivered. Here, we describe the microencapsulation of the model enzyme bile salt
      hydrolase (Bsh) using whey protein-gum arabic microencapsulates for food-grade
      and targeted enzyme delivery in the proximal region of the small intestine.
      Furthermore, the efficacy of enteric coating microencapsulates for site-specific
      enzyme delivery was compared in vitro with living Lactobacillus plantarum WCFS1
      bacteria that endogenously produce the Bsh enzyme. Microencapsulates allowed
      highly effective protection of the enzyme under gastric conditions. Moreover, Bsh
      release under intestinal conditions appeared to be very efficient, although in
      the presence of pancreatin, the Bsh activity decreased in time due to proteolytic
      degradation. In comparison, L. plantarum appeared to be capable to withstand
      gastric conditions as well as pancreatin challenge. Delivery using encapsulates
      and live bacteria each have different (dis)advantages that are discussed. In
      conclusion, live bacteria and food-grade microencapsulates provide alternatives
      for dedicated enteric delivery of specific enzymes, and the choice of enzyme to
      be delivered may determine which mode of delivery is most suitable.

PMID- 18729460
TI  - Ethanol effect on the structure of beta-lactoglobulin b and its ligand binding.
AB  - The changes of structure and ligand binding properties of beta-LG B have been
      studied by fluorescence and circular dichroism spectroscopy in ethanolic
      solutions. Fluorescence measurements of retinol/beta-LG interactions at 480 nm in
      various ethanol concentrations show that the maximal fluorescence intensity
      induced by this interaction between retinol and beta-LG is observed around 20%
      v/v of ethanol. It is reduced to zero at 40% and 50% of ethanol. These results
      suggest that there are two distinct structural changes in beta-LG occurring
      between 20% and 30% and around 40% of ethanol. The first transition, which
      increases affinity and the apparent number of binding sites for retinol, may be
      related or similar to the Tanford transition. The strong quenching of retinol
      emission at 480 nm in 40% of ethanol indicates the radical transformation of beta
      LG tertiary structure and the release of retinol. CD spectra at the aromatic
      region show that secondary and tertiary structures of beta-LG are not
      significantly affected between 0% and 20% of ethanol. In 30% of ethanol, beta
      sheet percentage of beta-LG decreases with respect to native beta-LG (from 55% to
      46%). beta-Sheet percentage in beta-LG increases in 40% and 50% alcohol (51% and
      53%) relative to 30% of ethanol, which also indicates the strong rearrangement of
      the secondary structure of beta-LG, while its tertiary structure and beta-LG
      interactions are radically changed.

PMID- 18729461
TI  - Heating affects the content and distribution profile of isoflavones in steamed
      black soybeans and black soybean koji.
AB  - Steamed black soybeans and black soybean koji, a potentially functional food
      additive, were subjected to heating at 40-100 degrees C for 30 min. It was found
      that steamed black soybeans and black soybean koji after heating at 80 degrees C
      or higher generally showed reduced contents of malonylglucoside, acetylglucoside,
      and aglycone isoflavone and an increased content of beta-glucoside. A lower
      reduction in malonylglucoside and acetylglucoside isoflavone but greater
      reduction in aglycone content was noted in steamed black soybeans compared to
      black soybean koji after a similar heat treatment. After 30 min of heating at 100
      degrees C, steamed black soybean retained ca. 90.3 and 83.8%, respectively, of
      its original malonylglucoside and acetylglucoside isoflavone, compared to lower
      residuals of 80.9 and 78.8%, respectively, for black soybean koji. In contrast,
      the heated black soybeans showed an aglycone residual of 68.0%, which is less
      than the 80.0% noted with the heated black soybean koji.

PMID- 18729462
TI  - Fractionation of honey carbohydrates using pressurized liquid extraction with
      activated charcoal.
AB  - This article describes the development of a new procedure that combines the use
      of activated charcoal and pressurized liquid extraction (PLE) to obtain enriched
      fractions of di- and trisaccharides from honey. Honey was adsorbed onto activated
      charcoal and packed into a PLE extraction cell. Optimum results were obtained at
      10 MPa and 40 degrees C using two consecutive PLE cycles: first, 1:99 (v/v)
      ethanol/water for 5 min and second, 50:50 (v/v) ethanol/water for 10 min. Di- and
      trisaccharide fractions were enriched after PLE treatment, accounting for 73% and
      8% of total carbohydrates, respectively. This procedure was also compared with
      other methodologies reported in the literature for the fractionation of honey
      carbohydrates (yeast treatment and extraction from activated charcoal). While the
      removal of monosaccharides was more efficient with yeast treatment, recovery of
      di- and trisaccharides was higher when either the PLE or the activated charcoal
      treatment was used. PLE was found to be the faster technique; it also required
      less solvent volume and minimized handling of the sample.

PMID- 18729463
TI  - Structural characteristics of phosphoramide derivatives as urease inhibitors.
      Requirements for activity.
AB  - Taking as a reference the structural characteristics of a set of compounds that
      act as jack bean ( Canavalia ensiformis) urease inhibitors, namely,
      phenylphosphorodiamidate (PPD), N- n-butylthiophosphorictriamide (NBPT), and N- n
      butylphosphorictriamide (NBPTO), we have studied the structure-activity
      relationships of a series of phosphoramide derivatives for which the activity as
      urease inhibitors in both in vitro and in vivo assays is known. Molecular
      modeling studies were carried out, and the results highlighted the relevance of
      characteristics such as the presence of intramolecular hydrogen bonds, the volume
      of the fragment involved in the enzyme interaction, and the degree of
      conformational freedom as well as the HOMO orbital and atomic orbital
      contributions to the HOMO orbital, electron density, and PEM distributions on the
      activity of these compounds as urease inhibitors. These data, along with the
      preliminary docking study carried out, allow us to propose a union mode to the
      active site of the enzyme for these compounds.

PMID- 18729464
TI  - Nondestructive prediction of total phenolics, flavonoid contents, and antioxidant
      capacity of rice grain using near-infrared spectroscopy.
AB  - Phytochemicals such as phenolics and flavonoids, which are present in rice
      grains, are associated with reduced risk of developing chronic diseases such as
      cardiovascular disease, type 2 diabetes, and some cancers. The phenolic and
      flavonoid compounds in rice grain also contribute to the antioxidant activity.
      Biofortification of rice grain by conventional breeding is a way to improve
      nutritional quality so as to combat nutritional deficiency. Since wet chemistry
      measurement of phenolic and flavonoid contents and antioxidant activity are time
      consuming and expensive, a rapid and nondestructive predictive method based on
      near-infrared spectroscopy (NIRS) would be valuable to measure these nutritional
      quality parameters. In the present study, calibration models for measurement of
      phenolic and flavonoid contents and antioxidant capacity were developed using
      principal component analysis (PCA), partial least-squares regression (PLS), and
      modified partial least-squares regression (mPLS) methods with the spectra of the
      dehulled grain (brown rice). The results showed that NIRS could effectively
      predict the total phenolic contents and antioxidant capacity by PLS and mPLS
      methods. The standard errors of prediction (SEP) were 47.1 and 45.9 mg gallic
      acid equivalent (GAE) for phenolic content, and the coefficients of determination
      ( r (2)) were 0.849 and 0.864 by PLS and mPLS methods, respectively. Both PLS and
      mPLS methods gave similarly accurate performance for prediction of antioxidant
      capacity with SEP of 0.28 mM Trolox equivalent antioxidant capacity (TEAC) and r
      (2) of 0.82. However, the NIRS models were not successful for flavonoid content
      with the three methods ( r (2) < 0.4). The models reported here are usable for
      routine screening of a large number of samples in early generation screening in
      breeding programs.

PMID- 18729466
TI  - Oxidative reactions during early stages of beer brewing studied by electron spin
      resonance and spin trapping.
AB  - An electron spin resonance (ESR)-based method was used for evaluating the levels
      of radical formation during mashing and in sweet wort. The method included the
      addition of 5% (v/v) ethanol together with the spin trap alpha-4-pyridyl(1-oxide)
      N- tert-butylnitrone (POBN) to wort, followed by monitoring the rate of
      formation of POBN spin adducts during aerobic heating of the wort. The presence
      of ethanol makes the spin trapping method more selective and sensitive for the
      detection of highly reactive radicals such as hydroxyl and alkoxyl radicals.
      Samples of wort that were collected during the early stages of the mashing
      process gave higher rates of spin adduct formation than wort samples collected
      during the later stages. The lower oxidative stability of the early wort samples
      was confirmed by measuring the rate of oxygen consumption during heating of the
      wort. The addition of Fe(II) to the wort samples increased the rate of spin
      adduct formation, whereas the addition of Fe(II) during the mashing had no effect
      on the oxidative stability of the wort samples. Analysis of the iron content in
      the sweet wort samples demonstrated that iron added during the mashing had no
      effect on the iron level in the wort. The moderate temperatures during the early
      steps of mashing allow the endogenous malt enzymes to be active. The potential
      antioxidative effects of different redox-active enzymes during mashing were
      tested by measuring the rate of spin adduct formation in samples of wort.
      Surprisingly, a high catalase dosage caused a significant, 20% reduction of the
      initial rate of radical formation, whereas superoxide dismutase had no effect on
      the oxidation rates. This suggests that hydrogen peroxide and superoxide are not
      the only intermediates that play a role in the oxidative reactions occurring
      during aerobic oxidation of sweet wort.

PMID- 18729465
TI  - Quantitation of methylxanthinic alkaloids and phenolic compounds in mate (Ilex
      paraguariensis) and their effects on blood vessel formation in chick embryos.
AB  - Methylxanthinic alkaloids and phenolic compounds are related to the therapeutic
      properties of Ilex paraguariensis infusions. Considering the known vascular
      tropism of xanthines, an aqueous extract (mate) and caffeine were evaluated on
      blood vessel formation, in connection with the analysis of those secondary
      metabolites, which was performed in young and mature leaf samples collected in
      three cultivation systems located in the southern region in Brazil (Santa
      Catarina State). Samples of young and mature leaves from a monoculture
      cultivation system (MC) showed the highest content of phenolic compounds (149.68
      microg/mL, young leaves; 135.50 microg/mL, mature leaves) and caffeine (young
      leaves, 148.07 microg/mL; mature leaves, 244.63 microg/mL) as compared to samples
      from agroforesty (AF) and shaded-native (NT) cultures. Theophylline was not
      detected in samples by reverse phase-high performance liquid chromatography, and
      mature leaves showed lower theobromine amounts (11.46 microg/mL). Treatments
      performed with mate aqueous extract and caffeine (1.03-4.12 microM/disk) in the
      yolk sac vascular membranes of 2-day-old chick embryos revealed pro-vasculo- and
      angiogenic properties as well as embryonic growth enhancement. These findings,
      uncoupled from any detectable embryotoxic effect, suggest a potential therapeutic
      and/or prophylactic use in cardiovascular disorders for caffeine and related
      constituents of mate plant extracts, an issue that waits further studies.

PMID- 18729467
TI  - A new catalytic Cu(II)/sparteine oxidant system for beta,beta-phenolic couplings
      of styrenyl phenols: synthesis of carpanone and unnatural analogs.
AB  - A new catalytic Cu(II)/sparteine system has been developed to promote beta,beta
      phenolic couplings of styrenyl phenols en route to carpanone and related
      unnatural congeners in yields exceeding 85%.

PMID- 18729469
TI  - Mathematical model for mixing reactants in a capillary microreactor by transverse
      diffusion of laminar flow profiles.
AB  - Transverse diffusion of laminar flow profiles (TDLFP) was recently suggested as a
      generic approach for mixing reactants inside a capillary microreactor.
      Conceptually, solutions of reactants are injected inside the capillary by high
      pressure as a series of consecutive plugs. Because of the laminar nature of the
      flow inside the capillary, the nondiffused plugs have parabolic profiles with
      predominantly longitudinal interfaces between the plugs. After the injection, the
      reactants are mixed by transverse diffusion across the longitudinal interfaces.
      TDLFP-based mixing is still in its infancy as only the principle was proved.
      Here, we develop the theory of TDLFP and introduce a dimensionless parameter,
      York number, which can be used in predicting the quality of TDLFP-based mixing.
      The theory uses a single simplifying assumption that the longitudinal diffusion
      is negligible; this assumption is readily satisfied. We then develop a numerical
      model of TDLFP and use it to simulate the concentration profiles of three
      reactants mixed by TDLFP in the capillary. The correlation between the York
      number and quality of mixing is analyzed. Two ways of improving the quality of
      TDLFP-based mixing are suggested and studied: (i) increasing the longitudinal
      interface between the plugs by a long last plug of a solvent and (ii) "shaking"
      the injected reactants by a series of alternating negative and positive pressure
      pulses. The developed theory and computational simulation of TDLFP will stimulate
      the practical use of capillary microreactors.

PMID- 18729470
TI  - In situ gamma-radiation: one-step environmentally benign method to produce gold
      palladium bimetallic nanoparticles.
AB  - Synthesis of gold-palladium bimetallic nanoparticles using in situ radioactivity
      from (198)Au isotope is reported in this paper. Gold solution spiked with
      (198)Au(III) has been mixed with PdCl2 solution in measured proportions in 50%
      polyethylene glycol solution. Au(III) and Pd(II) are reduced, and nanoparticles
      are formed due to radiolysis of the polymer solution. The solution has been
      characterized by UV-visible spectra, and the actual size has been determined
      using transmission electron microscopy in conjugation with energy dispersive X
      ray measurements.

PMID- 18729468
TI  - Combination chemotherapy and photodynamic therapy with fab' fragment targeted
      HPMA copolymer conjugates in human ovarian carcinoma cells.
AB  - The biological activities of sequential combinations of anticancer drugs, SOS
      thiophene (SOS) and mesochlorin e 6 monoethylenediamine (Mce 6), in the form of
      free drugs, nontargeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug
      conjugates, P-GFLG-Mce 6 and P-GFLG-SOS (P is the HPMA copolymer backbone and
      GFLG is the glycylphenylalanylleucylglycine spacer), and Fab'-targeted HPMA
      copolymer-drug conjugates, P-(GFLG-Mce 6)-Fab' and P-(GFLG-SOS)-Fab' (Fab' from
      OV-TL16 antibodies complementary to CD47), were evaluated against human ovarian
      carcinoma OVCAR-3 cells. Mce 6, SOS, P-GFLG-Mce 6, P-GFLG-SOS, P-(GFLG-Mce 6)
      Fab', and P-(GFLG-SOS)-Fab', when used as single agents or in binary combination,
      exhibited cytotoxic activities against OVCAR-3 cells, as determined using a
      modified MTT assay. The binding and internalization of P-(GFLG-Mce 6)-Fab' and P
      (GFLG-SOS)-Fab' by OVCAR-3 cells were visualized by confocal microscopy and flow
      cytometry. The results confirmed an enhanced biorecognition by OVCAR-3 cells of
      Fab'-targeted HPMA copolymer conjugates over nontargeted conjugates. The median
      effect analysis and the determination of the combination index (CI) were used to
      describe the drug interaction and quantify the synergism, antagonism, or
      additivity in anticancer effects. The sequential combinations of SOS+Mce 6 and P
      GFLG-SOS+P-GFLG-Mce 6 displayed very strong synergism to synergism in the entire
      range of cell inhibition levels ( f a = 0.5 - 0.95). The P-(GFLG-SOS)-Fab'+P
      (GFLG-Mce 6)-Fab' exhibited a strong synergism for f a values up to about 0.85,
      but showed synergistic effect and nearly additive effect at f a = 0.9 and 0.95,
      respectively. These observations support the continuation of in vivo
      investigations of these conjugates for the treatment of ovarian cancer.

PMID- 18729471
TI  - Sequence confirmation of modified oligonucleotides using chemical degradation,
      electrospray ionization, time-of-flight, and tandem mass spectrometry.
AB  - We report the sequencing of highly modified oligonucleotides containing a mixture
      of 2'-deoxy, 2'-fluoro, 2'-O-methyl, abasic, and ribonucleotides. The passenger
      and guide strands each containing 48% and 86% of modified nucleotides,
      respectively, are representative sequences of synthetic short interfering RNAs
      (siRNAs). We describe herein the sequence confirmation of both strands using a
      series of robust chemical reactions, followed by analysis via ESI-TOF and ion
      trap mass spectrometry (ITMS). The following method enables the rapid sequence
      confirmation of highly modified oligonucleotides.

PMID- 18729472
TI  - Nanostructured diamond-like carbon on digital versatile disc as a matrix-free
      target for laser desorption/ionization mass spectrometry.
AB  - A nanostructured diamond-like carbon (DLC) coated digital versatile disk (DVD)
      target is presented as a matrix-free sample support for application in laser
      desorption/ionization mass spectrometry (LDI-MS). A large number of vacancies,
      defects, relative sp(2) carbon content, and nanogrooves of DLC films support the
      LDI phenomenon. The observed absorptivity of DLC is in the range of 305-330 nm
      (nitrogen laser, 337 nm). The universal applicability is demonstrated through
      different analytes like amino acids, carbohydrates, lipids, peptides, and other
      metabolites. Carbohydrates and amino acids are analyzed as sodium and potassium
      adducts. Peptides are detectable in their protonated forms, which avoid the extra
      need of additives for ionization. A bovine serum albumin (BSA) digest is analyzed
      to demonstrate the performance for peptide mixtures, coupled with the material
      enhanced laser desorption/ionization (MELDI) approach. The detection limit of the
      described matrix-free target is investigated to be 10 fmol/microL for [Glu(1)]
      fibrinopeptide B (m/z 1570.6) and 1 fmol/microL for L-sorbose (Na(+) adduct). The
      device does not require any chemical functionalization in contrast to other
      matrix-free systems. The inertness of DLC provides longer lifetimes without any
      deterioration in the detection sensitivity. Broad applicability allows high
      performance analysis in metabolomics and peptidomics. Furthermore the DLC coated
      DVD (1.4 GB) sample support is used as a storage device for measured and
      processed data together with sampling on a single device.

PMID- 18729473
TI  - Control of ion distortion in field asymmetric waveform ion mobility spectrometry
      via variation of dispersion field and gas temperature.
AB  - Field asymmetric waveform ion mobility spectrometry (FAIMS) has emerged as an
      analytical tool of broad utility, especially in conjunction with mass
      spectrometry. Of particular promise is the use of FAIMS and 2-D ion mobility
      methods that combine FAIMS with conventional IMS to resolve and characterize
      protein and other macromolecular conformers. However, FAIMS operation requires a
      strong electric field, and ions are inevitably heated by energetic collisions
      with buffer gas molecules. This may induce ion isomerization or dissociation,
      which distort the separation properties of FAIMS (and subsequent stages) or
      reduce instrumental sensitivity. As FAIMS employs a periodic waveform, whether
      those processes are controlled by ion temperature at maximum or average field
      intensity has been debated. Here we address this issue by measuring the unfolding
      of compact ubiquitin ion geometries as a function of waveform amplitude
      (dispersion field, E(D)) and gas temperature, T. The field heating is quantified
      by matching the dependences of structural transitions on E(D) and T: increasing
      E(D) from 12 to 16 or from 16 to 20 kV/cm is equivalent to heating the (N2) gas
      by approximately 15-25 degrees C. The magnitude of field heating for any E(D) can
      be estimated using the two-temperature theory, and raising E(D) by 4 kV/cm
      augments heating by approximately 15-30 degrees C for maximum and approximately 4
      8 degrees C for average field in the FAIMS cycle. Hence, isomerization of ions in
      FAIMS appears to be determined by the excitation at waveform peaks.

PMID- 18729475
TI  - Systematic investigation of optimal aptamer immobilization for protein-microarray
      applications.
AB  - Aptamers are short single-stranded DNA or RNA oligonucleotides that can bind to a
      wide range of target molecules with high affinity and specificity. As nucleic
      acids, aptamers can undergo denaturation, but the process is reversible. As a
      result of this stability and the possibility of automated selection of aptamers,
      these oligonucleotides are highly promising capture molecules in microarray
      formats. In this study, his-tagged proteins and an aptamer directed against the
      his-tag were chosen as a model system. Different factors affect the activity of
      aptamers immobilized on a solid support like a microarray surface. The
      orientation of the immobilized aptamer plays an important role in correct aptamer
      folding and, thus, in effective binding of the corresponding target. Other
      important parameters identified in this work are the microarrays' surface charge
      as well as the length of the spacer between aptamer and solid support. These
      parameters were investigated systematically, resulting in the development of an
      aptamer-based microarray for detection of his-tagged proteins. The general
      applicability of the developed immobilization strategy was demonstrated by
      utilization of three different aptamers.

PMID- 18729474
TI  - Interactions between multiple cell types in parallel microfluidic channels:
      monitoring platelet adhesion to an endothelium in the presence of an anti
      adhesion drug.
AB  - A simple method for immobilizing endothelial cells in the channels of a
      microfluidic device fabricated with soft lithography is presented that requires
      no surface oxidation of the substrate material used in conjunction with the
      microfluidic device and is operable even with a reversible seal. Specifically,
      optimal conditions for culturing bovine pulmonary artery endothelial cells
      (bPAECs) to the surface of a Petri dish were investigated. The parameters
      investigated included fibronectin concentration, temperature, seeding density,
      and immobilization time. To enhance the utility of the device, all optimization
      studies, and studies involving platelet adhesion to the immobilized endothelium,
      were performed in parallel channels, thereby enabling improved throughput over a
      single channel device. The optimal conditions for cell immobilization included
      coating the Petri dish with 100 microg/mL fibronectin, a seeding cell density of
      1.00 x 10(5) cells mL(-1), and an immobilization time of 90 min at 37 degrees C.
      The device was then employed to monitor the physical interaction (adhesion) of
      platelets to the immobilized endothelium in the presence of a known platelet
      activator (ADP) and a drug inhibitor of platelet activation. The number of
      platelets adhering to the endothelial cells in the channels increased from 17.0
      +/- 2.3 in the absence of ADP to 63.2 +/- 2.4 in the presence of 5.00 microM ADP.
      Moreover, the data presented here also shows that inhibition of endothelium
      nitric oxide (NO) production, a recognized inhibitor of platelet adhesion to the
      endothelium, increased the number of platelets adhering to the surface to 35.4 +/
      1.0. In the presence of NO inhibition and 5.00 microM ADP, the affect on
      platelet adhesion was further increased to 127 +/- 5.2. Finally, this device was
      employed to investigate the effect of a drug known to inhibit platelet adhesion
      (clopidogrel) and, in the presence of the drug, the platelet adhesion due to
      activation by 5.00 microM ADP decreased to 24.0 +/- 3.8. This work is the first
      representation of multiple cell types physically interacting in the channels of a
      microfluidic device and further demonstrates the potential of these devices in
      the drug discovery process and drug efficacy studies.

PMID- 18729477
TI  - Bacterial DNA sample preparation from whole blood using surface-modified Si
      pillar arrays.
AB  - A novel bacterial DNA sample preparation device for molecular diagnostics has
      been developed. On the basis of optimized conditions for bacterial adhesion,
      surface-modified silicon pillar arrays for bacterial cell capture were
      fabricated, and their ability to capture bacterial cells was demonstrated. The
      capture efficiency for bacterial cells such as Escherichia coli, Staphylococcus
      epidermidis, and Streptococcus mutans in buffer solution was over 75% with a flow
      rate of 400 microL/min. Moreover, the proposed method captured E. coli cells
      present in 50% whole blood effectively. The captured cells from whole blood were
      then in- situ lyzed on the surface of the microchip, and the eluted DNA was
      successfully amplified by qPCR. These results demonstrate that the full process
      of pathogen capture to DNA isolation from whole blood could be automated in a
      single microchip.

PMID- 18729479
TI  - William von Eggers Doering's many research achievements during the first 65 years
      of his career in chemistry.
AB  - This Account highlights William von Eggers Doering's important discoveries in
      many fields of chemistry. His synthetic and mechanistic studies have contributed
      to areas including non-benzenoid aromatics, carbenes, pericyclic reactions, and
      diradical intermediates. Doering's synthesis with L. H. Knox of the highly stable
      tropylium ion and their investigation of its reactivity were the starting point
      for the development of the field of non-benzenoid aromatics. Working with A. K.
      Hoffmann, Doering demonstrated the synthesis of dichloro- and dibromocarbene by
      base-induced alpha elimination of HCl or HBr from CHCl3 or CHBr3 under anhydrous
      conditions. These results allowed for the synthesis of a variety of cyclopropanes
      and derivatives including allenes. Using 14C labeling experiments, Doering and
      Prinzbach showed that the mechanism of insertion of singlet methylene into a C-H
      bond was a concerted process.In their work on the Cope rearrangement, Doering and
      Roth's outstanding stereochemical analysis showed that the rearrangement of
      acyclic 1,5-hexadienes proceeds concertedly, passing over a chairlike transition
      state. This work has had an enormous impact on the understanding of
      stereochemical control in synthetic organic chemistry, and many fruitful
      applications in synthesis have stemmed directly from this finding. Transition
      state resonance structures analogous to those for ground-state aromatics can
      qualitatively explain the relatively large substituent effects on the rate of the
      Cope rearrangement. However, quantum chemical calculations have quantitatively
      described these effects. The rapid degenerate Cope rearrangements in the cis
      divinylcyclopropane units of 3,4-homotropilidene, barbaralone, and bullvalene
      establish these molecules as having fluxional structures. The unique molecule
      bullvalene has more than 1.2 million possible structures interconnected by
      degenerate Cope rearrangements, which average all H and all C atoms. Doering has
      also examined stepwise thermal reorganizations that pass through intermediary 1,3
      or 1,4-diradicals and do not show conformational equilibration as would be
      expected for classical intermediates. Doering calls these processes "not
      obviously concerted". He discusses "continuous diradicals" as transition states
      and rationalizes the course of these reactions through the concept of a "caldera"
      (a flat surface with small energy wells as found on the top of volcanoes).The
      understanding of fundamental chemical reactions remains the focus of Doering's
      research. In his terms, "understanding" means not only gaining deep insight but
      also the intellectual control that allows researchers to predict a reaction's
      course. Because the interplay between theory and experiment has led to great
      progress in this predictive ability, Doering's experimental work has provided an
      important input for computational chemistry and to the essential understanding of
      chemical reactions.

PMID- 18729478
TI  - ABTS-modified multiwalled carbon nanotubes as an effective mediating system for
      bioelectrocatalytic reduction of oxygen.
AB  - The ability of such a common redox mediator as 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonate) (ABTS) to undergo sorption on carbon surfaces
      is explored here to convert multiwalled carbon nanotubes (CNTs) into a stable
      colloidal solution of ABTS-modified carbon nanostructures, the diameters of which
      are approximately 10 nm (as determined by transmission electron microscopy).
      Subsequently, inks composed of fungal laccase (Cerrena unicolor) mixed with the
      dispersion of ABTS-modified CNTs and stabilized with Nafion, were deposited on
      glassy carbon and successfully employed to the reduction of oxygen in McIlvain
      buffer at pH 5.2. For comparison, the systems utilizing only ABTS-free CNTs and
      laccase as well as ABTS-modified CNTs did not show appreciable activity toward
      the oxygen reduction. The three-dimensionally distributed ABTS-modified CNTs are
      expected to improve the film's overall conductivity and to facilitate electrical
      connection between the electrode and the enzyme. The network film of ABTS
      modified CNTs is rigid, and it is characterized by charge propagation
      capabilities comparable to the conventional redox polymers. The whole concept of
      utilization of CNTs modified with ultrathin films of redox mediators in the
      preparation of efficient bioelectrocatalytic films seems to be of general
      importance to electroanalytical chemistry and to the development of biosensors.

PMID- 18729476
TI  - Detection and characterization of altered conformations of protein
      pharmaceuticals using complementary mass spectrometry-based approaches.
AB  - Unlike small-molecule drugs, the conformational properties of protein
      biopharmaceuticals in solution are influenced by a variety of factors that are
      not solely defined by their covalent chemical structure. Since the conformation
      (or higher order structure) of a protein is a major modulator of its biological
      activity, the ability to detect changes in both the higher order structure and
      conformational dynamics of a protein, induced by an array of extrinsic factors,
      is of central importance in producing, purifying, and formulating a commercial
      biopharmaceutical with consistent therapeutic properties. In this study we
      demonstrate that two complementary mass spectrometry-based approaches (analysis
      of ionic charge-state distribution and hydrogen/deuterium exchange) can be a
      potent tool in monitoring conformational changes in protein biopharmaceuticals.
      The utility of these approaches is demonstrated by detecting and characterizing
      conformational changes in the biopharmaceutical product interferon beta-1a (IFN
      beta-1a). The protein degradation process was modeled by inducing a single
      chemical modification of IFN-beta1a (alkylation of its only free cysteine residue
      with N-ethylmaleimide), which causes significant reduction in its antiviral
      activity. Analysis of IFN-beta1a ionic charge-state distributions unequivocally
      reveals a significant decrease of conformational stability in the degraded
      protein, while hydrogen/deuterium exchange measurements provide a clear
      indication that the higher order structure is affected well beyond the covalent
      modification site. Importantly, neither technique required that the location or
      indeed the nature of the chemical modification be known prior to or elucidated in
      the process of the analysis. In contrast, application of the standard
      armamentarium of biophysical tools, which are commonly employed for quality
      control of protein pharmaceuticals, met with very limited success in detection
      and characterization of conformational changes in the modified IFN-beta1a. This
      work highlights the role mass spectrometry can and should play in the
      biopharmaceutical industry beyond the presently assigned task of primary
      structure analysis.

PMID- 18729480
TI  - Advances in molecular design and synthesis of regioregular polythiophenes.
AB  - Regioregular poly(3-alkylthiophene)s (rrP3ATs) are an important class of pi
      conjugated polymers that can be used in plastic electronic devices such as solar
      cells and field-effect transistors. rrP3ATs can be ordered in three dimensions:
      conformational ordering along the backbone, pi-stacking of flat polymer chains,
      and lamellar stacking between chains. All of these features lead to the excellent
      electrical properties of these materials. Creative molecular design and advanced
      synthesis are critical in controlling the properties of the materials as well as
      their device performance. This Account reports the advances in molecular design
      of new functional polythiophenes as well as the associated polymerization
      methods. Many functionalized regioregular polythiophenes have been designed and
      synthesized and show fascinating properties such as high conductivity, mobility,
      chemosensitivity, liquid crystallinity, or chirality. The methods for the
      synthesis of rrP3ATs are also applicable to other functional side chains. Di- and
      triblock copolymers consisting of rrP3AT and polyacrylate or polystyrene have
      also been successfully synthesized, which can facilitate the assembly of the
      polythiophene segments. The synthesis of rrP3ATs has evolved into a simple and
      economical system in which the synthesis can be carried out quickly at room
      temperature and is thus suitable for large-scale manufacturing. Intensive study
      has revealed that the regioregular polymerization of 3-alkylthiophenes proceeds
      by a chain-growth mechanism and can be made into a living system. This feature
      enables precise control of the molecular weight and facile end-group
      functionalization of the polymer chains, leading to tailor-made regioregular
      polythiophenes for specific applications. In addition, researchers have recently
      designed and synthesized regiosymmetric polythiophenesthese are regioregular but
      not coupled in a head-to-tail fashionby various methods. These reports indicate
      that these regiosymmetric polymers show very high mobilities when used in field
      effect transistors due to their highly ordered structure. The remarkable
      performance of regioregular polythiophenes in recent years has allowed for the
      rapid development in printable electronics and seems destined to lead to further
      advances in this field.

PMID- 18729481
TI  - Microstructures in aqueous solutions of a polyoxyethylene trisiloxane surfactant
      and a cosurfactant studied by SANS and NMR self-diffusion.
AB  - Microemulsion samples of a polyoxyethylene trisiloxane surfactant, water, and 1
      decanol are investigated using pulsed field gradient NMR and small-angle neutron
      scattering (SANS) to determine the solution structure. The surfactant/decanol
      weight ratio has been kept constant at values of 10:1, 8:1, and 6:1 under
      variation of water content. The temperature was 32 degrees C for the measurement
      series at the weight ratio of 10:1 to avoid phase separation at high water
      content. Also, aqueous surfactant solution samples have been investigated as a
      function of composition and temperature. Water-rich samples consist of micelles
      that are close to spherical at very low surfactant concentration and grow into
      anisometric, that is, oblate formed aggregates, at higher surfactant (or
      surfactant and decanol) concentration. The aggregates grow with increasing
      temperature, most probably due to dehydration of the hydrophilic groups. In a
      concentration range around 50 wt % water, the systems form bicontinuous
      structures. SANS data are used to estimate surfactant film properties using a
      model developed for interpretation of neutron scattering data from related
      systems.

PMID- 18729482
TI  - Adsorption hysteresis in self-ordered nanoporous alumina.
AB  - We performed systematic adsorption studies using self-ordered nanoporous anodic
      aluminum oxide (AAO) in an extended range of mean pore diameters and with
      different pore topologies. These matrices were characterized by straight
      cylindrical pores having a narrow pore size distribution and no interconnections.
      Pronounced hysteresis loops between adsorption and desorption cycles were
      observed even in the case of pores closed at one end. These results are in
      contrast with macroscopic theoretical models and detailed numerical simulations
      of the adsorption in a single pore. Extensive measurements involving adsorption
      isotherms, reversal curves, and subloops carried out in closed-bottom pores
      suggest that the pores do not desorb independently from one another.

PMID- 18729483
TI  - Assembly of nanozeolite monolayers on the gold substrates of piezoelectric
      sensors.
AB  - Colloidal zeolites NaA (LTA structure type) and ZSM-5 (MFI-type) with crystal
      diameters of about 100 nm were synthesized as building blocks for the formation
      of microporous self-limiting monolayers on the piezo-active area (gold
      electrodes) of a quartz crystal microbalance (QCM). Two different coupling
      strategies were explored, concerning the modification of either the gold
      substrate or the external zeolite crystal surface with a bifunctional molecular
      interface. Diverse analytical methods were employed to fully characterize the
      materials (dynamic light scattering, X-ray diffraction, infrared and Raman
      spectroscopy, solid state 29Si NMR spectroscopy, N2 sorption) and to study the
      process of coupling the zeolite crystals to the gold surface (reflection
      absorption IR spectroscopy, scanning electron microscopy). The molecularly
      selective sensing behavior of these zeolite-coated devices is demonstrated by
      measuring the full adsorption isotherms of n-butane and i-butane in the
      microporous films.

PMID- 18729484
TI  - Interaction forces between silica surfaces in aqueous solutions of cationic
      polymeric flocculants: effect of polymer charge.
AB  - Three cationic polymers with molecular weights and charge density of 3.0 x 10(5)
      g/mol and 10% (D 6010), 1.1 x 10(5) g/mol and 40% (D6040), and 1.2 x 10(5) g/mol
      and 100% (D6099) were investigated in aqueous NaCl solutions in the presence of
      silica. The atomic force microscope (AFM) colloidal probe technique was used to
      determine silica interparticle interaction forces, which were compared to
      macroscopic information on the strength of interactions such as compressive yield
      stress measurements. It was found that in 30 mM NaCl solution the 10% charged
      polymer produced steric repulsion upon approach and long-range adhesion with
      multiple pull off events upon retraction at the optimum flocculation
      concentration. This suggests that the polymer was adsorbed in a conformation
      where segments extend from the surface, resulting in bridging flocculation. The
      40 and 100% charged polymers produced attraction upon approach and strong
      adhesion with snap out from contact upon separation at optimum polymer dosages.
      This suggests that these polymers are adsorbed with flat conformations and is
      typical of charge neutralization or patch attraction. The attractions for 40 and
      100% charged polymers measured with the AFM are significantly larger than for the
      10% charged polymer. The polymer dose that produced the optimum flocculation and
      the maximum compressive yield stress typically corresponded to the polymer
      concentration that produced the maximum adhesion for each polymer. It was found
      that the magnitude of the adhesive force was more significant in determining the
      compressive yield stresses of the silica particle sediments than the aggregate
      size and structure.

PMID- 18729485
TI  - Functionalization of self-organized TiO2 nanotubes with Pd nanoparticles for
      photocatalytic decomposition of dyes under solar light illumination.
AB  - Self-organized, vertically oriented TiO2 nanotube arrays prepared by the
      sonoelectrochemical anodization method are functionalized with palladium (Pd)
      nanoparticles of approximately 10 nm size. A simple incipient wetness method is
      adopted to distribute the Pd nanoparticles uniformly throughout the TiO2
      nanotubular surface. This functionalized material is found to be an excellent
      heterogeneous photocatalyst that can decompose nonbiodegradable azo dyes (e.g.,
      methyl red and methyl orange) rapidly (150-270 min) and efficiently (100%) under
      ambient conditions using simulated solar light in the absence of any external
      oxidative radicals such as hydrogen peroxide.

PMID- 18729486
TI  - Extreme resistance of superhydrophobic surfaces to impalement: reversible
      electrowetting related to the impacting/bouncing drop test.
AB  - The paper reports on the comparison of the wetting properties of superhydrophobic
      silicon nanowires (NWs), using drop impact impalement and electrowetting (EW)
      experiments. A correlation between the resistance to impalement on both EW and
      drop impact is shown. From the results, it is evident that when increasing the
      length and density of NWs (i) the thresholds for drop impact and EW
      irreversibility increase and (ii) the contact-angle hysteresis after impalement
      decreases. This suggests that the structure of the NW network could allow for
      partial impalement, hence preserving the reversibility, and that EW acts the same
      way as an external pressure. The most robust of our surfaces shows a threshold to
      impalement higher than 35 kPa, while most of the superhydrophobic surfaces tested
      so far have impalement thresholds smaller than 10 kPa.

PMID- 18729487
TI  - Micellization and adsorption of a series of succinimide dispersants.
AB  - The efficiency of a series of nonionic dispersants at stabilizing carbon-rich
      particles in oil was evaluated. The dispersants were synthesized by coupling a
      polyamine to two polyisobutylenes terminated at one end with a succinic anhydride
      (PIBSA). Their chemical composition was characterized by FTIR absorption. The
      associative strength of the dispersants was determined from their ability to self
      associate in solution into reverse micelles. Their critical micelle concentration
      (CMC) and aggregation number (Nagg) were determined by fluorescence in an apolar
      solvent, namely hexane. The associative strength of the dispersants was found to
      increase with increasing number of secondary amines in the polyamine core. The
      adsorption isotherms describing the adsorption of the dispersants onto carbon
      black particles were determined and showed the existence of two binding regimes
      for the dispersants having more amines in their polar core. Much stronger binding
      occurred at dispersant concentration lower than the CMC. The weaker binding
      observed at dispersant concentrations larger than the CMC is believed to result
      from the dispersants having to compete between micellization and adsorption at
      concentrations above the CMC.

PMID- 18729489
TI  - Rapid micropatterning of mesoporous silica film by site-selective low-energy
      electron beam irradiation.
AB  - Rapid microfabrication of mesoporous silica film at low temperature was achieved
      with low-energy electron beam (LEEB) irradiation. A mesostructured film
      (thickness approximately 200 nm), which was prepared through hydrolysis and
      condensation of tetramethoxysilane in the presence of hexadecyltrimethylammonium
      chloride, was irradiated with LEEB at 25 kV and 300 microA under pressures of 10
      and 1000 Pa. The surfactant molecules can be eliminated completely at
      temperatures less than 40 degrees C after only 10 min (10 Pa) and 5 min (1000 Pa)
      of irradiation, resulting in conversion to a highly ordered mesoporous silica
      film without cracking. The LEEB-irradiated film also showed reasonable chemical
      resistance toward dilute hydrofluoric acid solution due to sufficient
      consolidation by cross-linking of silicate networks during the irradiation. The
      unirradiated regions were etched away preferentially to the irradiated areas;
      therefore, rapid micropatterning of the mesoporous silica film was possible by
      area-selective LEEB irradiation followed by chemical etching.

PMID- 18729488
TI  - Synthesis and aggregation behavior of perylenetetracarboxylic diimide trimers
      with different substituents at bay positions.
AB  - Three perylene tetracarboxylic diimide (PDI) trimers substituted with different
      side groups at the bay positions were prepared with the triazine ring as a
      linkage. The free rotation of C-N-C bonds between the triazine ring and the PDI
      unit provide these molecules with some flexibility. The UV-vis absorption and
      fluorescence spectra of these three compounds show different concentration
      dependent behaviors, which depend on the side groups at the bay positions.
      Significant aggregation in organic solvents was revealed by the electronic
      absorption and emission spectra as well as the fluorescence quantum yield
      calculation. The aggregation behavior of these compounds in the solid state were
      investigated by X-ray diffraction (XRD), and the morphology of the aggregates was
      examined by atomic force microscopy (AFM). The aggregation of trimer 1 with two
      phenoxy groups at the 1 and 7 positions results in long nanofibers whereas
      trimers 2 and 3 with dipiperidinyl groups or tetraphenoxyl groups at the bay
      positions form only particles. The results of this research revealed that PDI
      trimers with flexible structures can also self-assemble into large ordered
      aggregates such as those with rigid structure. This information is believed to be
      useful in the design of novel nanoorganic materials.

PMID- 18729490
TI  - Capping ligand effects on the amorphous-to-crystalline transition of CdSe
      nanoparticles.
AB  - Amorphous CdSe nanoparticles were prepared by a base-catalyzed room-temperature
      reaction between cadmium nitrate and selenourea, with dodecanethiol as a capping
      ligand. The nanoparticle size could be controlled from 1.9 to 3.6 nm by
      increasing the water concentration in the reaction. When the nanoparticles were
      heated in a pyridine suspension, excitonic peaks appeared in the initially
      featureless optical absorption spectra. By changing the suspension solvent and
      the capping ligand and its concentration, it was shown that the dynamic surface
      exchange between the ligand and pyridine controls the crystallization process.
      This phenomenon was interpreted as a surface rigidity effect imposed by the
      ligand, whose importance was separately evidenced on the dried nanoparticles by
      the evolution of X-ray diffraction patterns and Raman spectra. In particular,
      both techniques showed that a threshold temperature is needed before
      crystallization occurs, and such a threshold was related to ligand desorption.
      The surface effect was directly visualized by high-resolution transmission
      electron microscopy observations of the amorphous particles, where
      crystallization under the electron beam was observed to start by the formation of
      a crystalline nucleus in the nanoparticle interior and then to extend to the
      whole structure.

PMID- 18729491
TI  - Effect of the number and placement of polymer tethers on the structure of
      concentrated solutions and melts of hybrid nanoparticles.
AB  - We have generalized and applied the microscopic polymer reference interaction
      site model theory to study intermolecular pair correlation functions and
      collective structure factors of concentrated solutions and melts of spherical
      nanoparticles carrying one, two, or four tethered polymer chains. A complex
      interplay of entropy (translational, conformational, and packing) and enthalpy
      (particle-particle attraction) leads to different structural arrangements with
      distinctive small- and wide-angle scattering signatures. Strong concentration
      fluctuations indicative of aggregate formation and/or a tendency for microphase
      separation occur as the total packing fraction and/or particle-particle
      attraction strength increase. In analogy with block copolymers, the microphase
      spinodal curve is estimated by extrapolation of the inverse of the amplitude of
      the small-angle scattering peak. As the number of tethered chains on
      nanoparticles increases, the microphase separation boundary spinodal occurs at
      higher particle-particle attraction strength or lower temperature. For
      nanoparticles with two tethers, increasing the angle between the attached chains
      shifts the microphase spinodal to lower temperatures. For nanoparticles with four
      tethers, the structural correlations are insensitive to various symmetric
      placements. The tendency for microphase transition is enhanced upon
      asymmetrically placing all four tethers on one side of the particle due to the
      high anisotropy of steric hindrance.

PMID- 18729492
TI  - Synthesis of atypical nanoparticles by the nanostructure in thin films of
      triblock copolymers.
AB  - We report the synthesis of atypical nanoparticles in donut shape with or without
      additional spherical nanoparticles attached on them by using the donut-like
      nanostructure formed in a thin film of triblock copolymers. In a high-humidity
      condition, a spin-coated film of triblock copolymer had donut-like holes
      consisting of the periphery and the center. By selective coordination of
      precursors of nanoparticles to the periphery of the holes, donut-like oxide
      nanoparticles were synthesized by oxygen plasma treatment on the film. Moreover,
      we were able to attach spherical nanoparticles on the donut-like nanoparticles by
      incorporating the other type of precursors to the center of the holes. Thus,
      beyond the synthesis of typical spherical nanoparticles, the results here extend
      potentials of the block copolymer approach to control the shape and complexity of
      nanoparticles.

PMID- 18729493
TI  - Streptococcus mutans and Streptococcus intermedius adhesion to fibronectin films
      are oppositely influenced by ionic strength.
AB  - Bacterial adhesion to protein-coated surfaces is mediated by an interplay of
      specific and nonspecific interactions. Although nonspecific interactions are
      ubiquitously present, little is known about the physicochemical mechanisms of
      specific interactions. The aim of this paper is to determine the influence of
      ionic strength on the adhesion of two streptococcal strains to fibronectin films.
      Streptococcus mutans LT11 and Streptococcus intermedius NCTC11324 both possess
      antigen I/II with the ability to bind fibronectin from solution, but S.
      intermedius binds approximately 20x less fibronectin than does the S. mutans
      strain under identical conditions. Both strains as well as fibronectin films are
      negatively charged in low ionic strength phosphate buffered saline (PBS, 10x
      diluted), but bacteria appear uncharged in high ionic strength PBS.
      Physicochemical modeling on the basis of overall cell surface properties (cell
      surface hydrophobicity and zeta potentials) demonstrates that both strains should
      favor adhesion to fibronectin films in a high ionic strength environment as
      compared to in a low ionic strength environment, where electrostatic repulsion
      between equally charged surfaces is dominant. Adhesion of S. intermedius to
      fibronectin films in a parallel plate flow chamber was completely in line with
      this modeling, while in addition atomic force microscopy (AFM) indicated stronger
      adhesion forces upon retraction between fibronectin-coated tips and the cell
      surfaces in high ionic strength PBS than in low ionic strength PBS. Thus, the
      dependence of the interaction on ionic strength is dominated by the overall
      negative charge on the interacting surfaces. Adhesion of S. mutans to fibronectin
      films, however, was completely at odds with theoretical modeling, and the strain
      adhered best in low ionic strength PBS. Moreover, AFM indicated weaker repulsive
      forces upon approach between fibronectin-coated tips and the cell surfaces in low
      ionic strength PBS than in high ionic strength PBS. This indicated that the
      dependence of the interaction on ionic strength is dominated by electrostatic
      attraction between oppositely charged, localized domains on the interacting
      surfaces, despite their overall negative charge. In summary, this study shows
      that physicochemical modeling of bacterial adhesion to protein-coated surfaces is
      only valid provided the number of specific interaction sites on the cell surfaces
      is low, such as on S. intermedius NCTC11324. Nonspecific interactions are
      dominated by specific interactions if the number of specific interaction sites is
      large, such as on S. mutans LT11. Its ionic strength dependence indicates that
      the specific interaction is electrostatic in nature and operative between
      oppositely charged domains on the interacting surfaces, despite the generally
      overall negatively charged character of the surfaces.

PMID- 18729494
TI  - Different internalization pathways of polymeric micelles and unimers and their
      effects on vesicular transport.
AB  - Efficient entry of synthetic polymers inside cells is a central issue in
      polymeric drug delivery. Though polymers are widely believed to interact
      nonspecifically with plasma membrane, we present unexpected evidence that
      amphiphilic block copolymers, depending on their aggregation state, can
      distinguish between caveolae- and clathrin-mediated endocytosis. A block
      copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), Pluronic
      P85 (P85), below critical micelle concentration (CMC) exists as single molecule
      coils (unimers) and above CMC forms 14.6 nm aggregated micelles with a
      hydrophobic PPO core and hydrophilic PEO shell. The internalization pathways of
      P85 in mammalian cells were elucidated using endocytosis inhibitors and
      colocalization with endocytosis markers (clathrin-specific antibodies and
      transferrin for clathrin and caveolin-1-specific antibodies and cholera toxin B
      for caveolae). Altogether, our results indicate that P85 unimers internalize
      through caveolae-mediated endocytosis, while P85 micelles internalize through
      clathrin-mediated endocytosis. Furthermore, at concentrations above 0.01% P85
      inhibits caveolae-mediated endocytosis (cholera toxin B), while having little or
      no effect on the clathrin-mediated endocytosis (transferrin). Selective
      interaction of Pluronic with caveolae may explain its striking pharmacological
      activities including inhibition of drug efflux transport, activation of gene
      expression, and dose-dependent hyperlipidemia.

PMID- 18729495
TI  - Amphiphilic block copolymers enhance cellular uptake and nuclear entry of
      polyplex-delivered DNA.
AB  - This work for the first time demonstrates that synthetic polymers enhance uptake
      and nuclear import of plasmid DNA (pDNA) through the activation of cellular
      trafficking machinery. Nonionic block copolymers of poly(ethylene oxide) and
      poly(propylene oxide), Pluronics, are widely used as excipients in pharmaceutics.
      We previously demonstrated that Pluronics increase the phosphorylation of IkappaB
      and subsequent NFkappaB nuclear localization as well as upregulate numerous
      NFkappaB-related genes. In this study, we show that Pluronics enhance gene
      transfer by pDNA/polycation complexes ("polyplexes") in a promoter-dependent
      fashion. Addition of Pluronic P123 or P85 to polyethyleneimine-based polyplexes
      had little effect on polyplex particle size but significantly enhanced pDNA
      cellular uptake, nuclear translocation, and gene expression in several cell
      lines. When added to polyplex-transfected cells after transfection, Pluronics
      enhanced nuclear import of pDNA containing NFkappaB binding sites, but have no
      effect on import of pDNA without these sites. Altogether, our studies suggest
      that Pluronics rapidly activate NFkappaB, which binds cytosolic pDNA that
      possesses promoters containing NFkappaB binding sites and consequently increase
      nuclear import of pDNA through NFkappaB nuclear translocation.

PMID- 18729496
TI  - Proteomic characterization of mouse cytosolic and membrane prostate fractions:
      high levels of free SUMO peptides are androgen-regulated.
AB  - The prostate is a relatively homogeneous tissue that is highly specialized in
      synthetic and secretory functions. The frequency of malignant growth explains its
      great clinical significance. We used here a combination of subcellular
      fractionation, 1-DE (one-dimensional gel electrophoresis) protein separation and
      mass spectrometry, to establish a prostate protein expression profile in mice.
      Analysis of proteins present in cytosolic (C) and membrane (P) prostate fractions
      led to the identification of 619 distinct proteins. A majority of abundant
      proteins were found to compose the metabolism and protein synthesis machinery.
      Those identified also correspond to known endoplasmic reticulum and Golgi
      residents, chaperones and anterograde cargos. They included a series of proteins
      involved in exocytic/endocytic trafficking. Among the signaling proteins, we
      identified the ubiquitin-like peptides smt3. We showed that both free small
      ubiquitin-related modifier SUMO-2/3 and SUMO-1 levels are subject to tight
      control by the androgen 5alpha-dihydrotestosterone (DHT). By contrast with SUMO
      2/3, free SUMO-1 peptides are particularly abundant in the prostate when compared
      with other tissues. Therefore, we report prostate protein expression profiles of
      cytosolic and membrane fractions in mice. Our data suggest that the identified
      free SUMO peptides play an important role in this secretory tissue.

PMID- 18729499
TI  - A physicochemical characterization of the interaction between DC-Chol/DOPE
      cationic liposomes and DNA.
AB  - A 1:1 mixture of the cationic lipid 3beta-[ N-( N', N'-dimethylaminoethane)
      carbamoyl]cholesterol hydrochloride (DC-Chol) and the zwitterionic lipid, 1,2
      dioleoyl- sn-glycero-3-phosphoetanolamine (DOPE), has been used to compact calf
      thymus DNA (CT-DNA) in aqueous buffered solution at 298.15 K. The formation
      process of this lipoplex has been analyzed by means of electrophoretic mobility,
      cryo-TEM, dynamic light scattering, and fluorescence spectroscopy techniques. The
      experimental results indicate that DC-Chol/DOPE liposomes are mostly spherical
      and unilamellar, with a mean diameter of around 99 +/- 10 nm and a bilayer with a
      thickness of 4.5 +/- 0.5 nm. In the presence of CT-DNA, DC-Chol/DOPE/CT-DNA
      lipoplexes are formed by means of a strong entropically driven surface
      electrostatic interaction, as confirmed by zeta potential and fluorescence
      results, as a consequence of which DNA is compacted and condensed at the surface
      of the cationic liposomes. The negative charges of DNA phosphate groups are
      neutralized by the positive charges of cationic liposomes at the isoneutrality L/
      D ratio, ( L/ D) varphi around 4, obtained from electrophoretic, fluorescence,
      and DLS measurements. The decrease in the fluorescence emission intensity of
      ethidium bromide, EtBr, initially intercalated between DNA base pairs, as long as
      the association between the biopolymer and the cationic liposomes takes place has
      permitted one to confirm its electrostatic character as well as to evaluate the
      different microenvironments of varying polarity of DNA-double helix, liposomes,
      and/or lipoplexes. Electronic microscopy reveals a rich scenario of possible
      nanostructures and morphologies for the lipoplexes, from unilamellar DNA-coated
      liposomes to multilamellar lipoplexes passing through cluster-like structures and
      several intermediate morphologies.

PMID- 18729497
TI  - Membrane glycoproteins associated with breast tumor cell progression identified
      by a lectin affinity approach.
AB  - The membrane glycoprotein component of the cellular proteome represents a
      promising source for potential disease biomarkers and therapeutic targets. Here
      we describe the development of a method that facilitates the analysis of membrane
      glycoproteins and apply it to the differential analysis of breast tumor cells
      with distinct malignant phenotypes. The approach combines two membrane extraction
      procedures, and enrichment using ConA and WGA lectin affinity columns, prior to
      digestion and analysis by LC-MS/MS. The glycoproteins are identified and
      quantified by spectral counting. Although the distribution of glycoprotein
      expression as a function of MW and p I was very similar between the two related
      cell lines tested, the approach enabled the identification of several distinct
      membrane glycoproteins with an expression index correlated with either a
      precancerous (MCF10AT1), or a malignant, metastatic cellular phenotype
      (MCF10CA1a). Among the proteins associated with the malignant phenotype, Gamma
      glutamyl hydrolase, CD44, Galectin-3-binding protein, and Syndecan-1 protein have
      been reported as potential biomarkers of breast cancer.

PMID- 18729500
TI  - Is ammonia a better solvent than water for contact ion pairs?
AB  - The existence of a charge-transfer-to-solvent process when a KI contact ion pair
      (CIP) dissolved in supercritical water (SCW) is excited by UV light was confirmed
      by use of electronic structure calculations applied to molecular dynamics
      trajectories. We observed similar behavior with fluid density as that found for
      the KI-CIP in supercritical ammonia (SCA); nevertheless, there are some distinct
      features in the two supercritical solvents. First, the effect of the solvent
      field due to the molecules lying beyond the first solvation shell is very
      different in SCW compared with that observed in SCA; in SCW it actually has a
      destabilizing effect over the ground and excited states. Second, our results for
      the thermodynamic behavior of the CIP indicate that SCA is better solvent than
      SCW for this species. The differences found can be attributed to the solvent
      molecules surrounding the CIP and bridging the two ions; they shield more
      efficiently the ion pair from long-range solvent effects in SCA. The different
      behavior is partially attributed to a stronger solvent-solvent interaction in SCW
      than in SCA.

PMID- 18729501
TI  - Transparent, hydrophobic composite aerogels with high mechanical strength and low
      high-temperature thermal conductivities.
AB  - A facile one-step polymer-incorporation sol-gel process, together with a surface
      modification and an ambient pressure drying processes, was developed to prepare
      silica-poly(vinylpyrrolidone) composite aerogels. These composite aerogels are
      with high hydrophobicity (static contact angle >120 degrees), good mechanical
      strength (Young's modulus of bending >30 MPa), and low high-temperature thermal
      conductivity (0.063 W/m-K at 300 degrees C), which are critical characteristics
      for practical applications of aerogels, particularly in energy saving areas, for
      long-term usage and large scale production.

PMID- 18729502
TI  - Equilibrium of multi-phase systems in gravitational fields.
AB  - Four necessary conditions for equilibrium of an isolated solid-liquid-vapor
      system in a gravitational field were derived by Ward and Sasges (1998) in a
      unified setting, by using an entropy maximization approach, and under the
      assumption that the liquid-vapor surface tension does not depend on elevation.
      These are thermal equilibrium, the Laplace and Young equations, and a condition
      on the chemical potentials of the components present in the system. Gibbs (1876)
      had obtained the Young equation in a derivation separate from the derivation of
      the other three conditions and by using an energy minimization approach. However,
      Gibbs had derived a more general form of the Laplace equation than Ward and
      Sasges's. Gibbs's equation contained a term expressing the contribution of the
      variation of surface tension with elevation. This equation has since been
      neglected by most of the scientific community. In the present paper, the same
      approach as Ward and Sasges's is used to derive, in an unified setting, the
      conditions for equilibrium of an isolated solid-liquid-vapor system in a
      gravitational field but under the assumption that the liquid-vapor surface
      tension may depend on elevation. The four well-known conditions for equilibrium
      are obtained, with Gibbs's generalized Laplace equation instead of the classical
      Laplace equation. The derivations in this paper were carried out for two
      different system geometries, namely, for a sessile drop and for a conical
      capillary tube, and similar conditions for equilibrium were obtained.

PMID- 18729503
TI  - Vesicle behavior: in search of explanations.
AB  - In this paper we will present a series of experiments in the general field of
      surfactant aggregates and, in particular, in vesicle chemistry, which have found
      no definitive explanation until now. These experiments concern vesicle self
      reproduction (in particular, the so-called matrix effect); the interaction
      between vesicle and RNA, where RNA appears capable of discriminating between
      vesicles differing slightly in size; the fusion of oppositely charged vesicles,
      which brings about unexpected behavior of size distribution; and some aspects of
      local concentration inside vesicles, which still lack clarification in terms of
      local versus overall concentration. The theoretical and experimental implications
      of this not yet understood behavior will be discussed, emphasizing that progress
      in the field must face the difficulty of applying thermodynamics to these
      kinetically trapped systems, and the general difficulty of understanding how
      kinetic and thermodynamic factors interplay with each other.

PMID- 18729505
TI  - Dewetting of thin amorphous solid water films and liquid-cubic ice coexistence in
      droplets studied using infrared-absorption and secondary-ion-mass spectroscopy.
AB  - The infrared absorption band of decoupled OD stretching vibration (4 mol% HOD in
      20-monolayer H2O) of amorphous solid water is red-shifted and sharpened at around
      160 K because of spontaneous nucleation. The crystal grows in a fluidized liquid
      that forms droplets on a Ni(111) substrate. The shape change and red-shift of a
      coupled OH band during crystallization are elucidated by a Mie particle
      scattering model, indicating that nanometer-size droplets are formed
      preferentially. The spontaneous nucleation at 160 K is bypassed when amorphous
      solid water is deposited on a crystallized water film; the crystals grow around
      nuclei at ca. 150 K, resulting in larger crystal grains that do not cause Mie
      scattering. However, the crystal grains behave like viscous droplets because
      their morphology changes continuously after the completion of crystallization.
      The coexisting liquid-like water is indistinguishable from cubic ice in local
      structure. This behavior resembles that of a quasiliquid formed during
      premelting.

PMID- 18729504
TI  - Ab initio fragment molecular orbital study of molecular interactions in liganded
      retinoid X receptor: specification of residues associated with ligand inducible
      information transmission.
AB  - The ab initio fragment molecular orbital calculations were performed for the
      alpha-subtype of the human retinoid X receptor (hRXRalpha) complex with its
      natural ligand 9- cis retinoic acid (9cRA) to quantitatively specify the key
      residues with important roles for the ligand inducible information transmission
      of RXR. In the RXR-9cRA complex, the transactivation helix 12 (H12) adopts a
      canonical agonist conformation, which just corresponds to the transcriptional
      activation function 2 activating domain core (AF2C). Through the analyses of
      molecular interactions by the second-order Moller-Plesset perturbation (MP2)
      method, it was proved that Trp305 and Leu436 of the AF2C binding pocket would be
      important for the stabilization of the H12 canonical agonist conformation, and,
      at the same time, for the recognition of the 9cRA molecule. Besides, through the
      analyses of orbital interactions by the local MP2 (LMP2) method, it was found
      that Trp305 and Leu436 would recognize the 9cRA molecule especially at its C19
      methyl group, which has been most notably targeted to modify for agonist and
      antagonist design. Moreover, on the basis of the relationships of molecular
      interactions, it was suggested that the interactions of Trp305 and Leu436 with
      AF2C residues would be significantly influenced by the interactions of Trp305 and
      Leu436 with 9cRA. Taken together, our findings quantitatively demonstrated that
      Trp305 and Leu436 would be the possible key residues for the information
      transmission in liganded RXR, accounting for their importance suggested by
      experiments. Altogether, these results substantiated that our approach is useful
      for the understanding of the detailed molecular mechanism underlying the
      transcriptional regulation of RXR and related nuclear receptors at the quantum
      mechanical level.

PMID- 18729506
TI  - Excited state proton transfer and solvent relaxation of a 3-hydroxyflavone probe
      in lipid bilayers.
AB  - The photophysics of a ratiometric fluorescent probe, N-[[4'- N, N-diethylamino-3
      hydroxy-6-flavonyl]methyl]- N-methyl- N-(3-sulfopropyl)-1-dodecanaminium, inner
      salt (F2N12S), incorporated into phospholipid unilamellar vesicles is presented.
      The reconstructed time-resolved emission spectra (TRES) unravels a unique feature
      in the photophysics of this probe. TRES exhibit signatures of both an excited
      state intramolecular proton transfer (ESIPT) and a dynamic Stokes shift
      associated with solvent relaxation in the lipid bilayer. The ESIPT is fast, being
      characterized by a risetime of approximately 30-40 ps that provides an
      equilibrium to be established between the excited normal (N*) and the ESIPT
      tautomer (T*) on a time scale of 100 ps. On the other hand, the solvent
      relaxation displays a bimodal decay kinetics with an average relaxation time of
      approximately 1 ns. The observed slow solvent relaxation dynamics likely embodies
      a response of nonspecific dipolar solvation coupled with formation of probe-water
      H-bonds as well as the relocation of the fluorophore in the lipid bilayer. Taking
      into account that ESIPT and solvent relaxation are governed by different
      physicochemical properties of the probe microenvironment, the present study
      provides a physical background for the multiparametric sensing of lipid bilayers
      using ESIPT based probes.

PMID- 18729507
TI  - Structural and dynamical properties of hydrogen fluoride in aqueous solution: an
      ab initio quantum mechanical charge field molecular dynamics simulation.
AB  - The novel ab initio quantum mechanical charge field (QMCF) molecular dynamics
      simulation at the Hartree-Fock level has been employed to investigate hydration
      structure and dynamics of hydrogen fluoride in aqueous solution. The average H-F
      bond length of 0.93 A obtained from the QMCF MD simulation is in good agreement
      with the experimental data. The HHF...Ow distance of 1.62 A was evaluated for the
      first hydration shell, and 2.00 A was observed for the FHF...Hw distance. The
      stability of hydrogen bonding is more pronounced in the hydrogen site of hydrogen
      fluoride, with a single water molecule in this part of the first hydration shell.
      A wide range of coordination numbers between 3 and 9 with an average value of 5.6
      was obtained for the fluorine site. The force constants of 819.1 and 5.9 N/m were
      obtained for the HHF-FHF and HHF...Ow interactions, respectively, proving the
      stability of the nondissociated form of hydrogen fluoride in aqueous solution.
      The mean residence times of 2.1 and 2.5 ps were determined for ligand exchange
      processes in the neighborhood of fluorine and hydrogen atoms of hydrogen
      fluoride, respectively, indicating a weak structure-making effect of hydrogen
      fluoride in water. The corresponding H-bond lifetimes attribute this effect to
      the H atom site of HF.

PMID- 18729508
TI  - Specific anion effects on enzymatic activity in nonaqueous media.
AB  - The present work shows that salt anions affect the activity of Pseudomonas
      cepacia lipase both in aqueous and in nonaqueous media (NAM) according to a
      Hofmeister series. The biocatalytic assay in water was the hydrolysis of p
      nitrophenyl acetate, whereas the esterification between 1-hexyl-beta-D
      galactopyranoside and palmitic acid was followed in an organic solvent. The solid
      lipase preparations to be used in NAM were obtained through lyophilization in the
      presence of concentrated solutions of Hofmeister salts (Na2SO4, NaH2PO4/Na2HPO4,
      NaCl, NaBr, NaI, NaSCN). Salts affect enzyme activity in organic media through
      two mechanisms: (1) enzyme protection during lyophilization; (2) enzyme
      activation during the reaction. At least in our case, the latter seems to be more
      important than the former. The decrease of the activation energy caused by the
      stabilization of the transition state due to "kosmotropic" anions might be the
      driving force of enzyme activation. According to the most recent findings,
      dispersion forces may be responsible of specific anion enzyme
      activation/deactivation in NAM.

PMID- 18729510
TI  - Experimental and theoretical studies of potassium cation interactions with the
      acidic amino acids and their amide derivatives.
AB  - The binding of K(+) to aspartic acid (Asp), glutamic acid (Glu), asparagine
      (Asn), and glutamine (Gln) is examined in detail by studying the collision
      induced dissociation (CID) of the four potassium cation-bound amino acid
      complexes with Xe using a guided ion beam tandem mass spectrometer (GIBMS).
      Formed by electrospray ionization, these complexes have energy-dependent CID
      cross sections that are analyzed to provide 0 K bond energies after accounting
      for unimolecular decay rates, internal energy of reactant ions, and multiple ion
      molecule collisions. Quantum chemical calculations for a number of geometric
      conformations of each K(+)(L) complex are determined at the B3LYP/6-311+G(d,p)
      level with single-point energies calculated at B3LYP, B3P86, and MP2(full) levels
      using a 6-311+G(2d,2p) basis set. Theoretical bond dissociation energies are in
      good agreement with the experimental values. This coordinated examination of both
      experimental work and quantum chemical calculations allows for a comprehensive
      understanding of the molecular interactions of K(+) with the Asx and Glx amino
      acids. K(+) binding affinities for the amide complexes are systematically
      stronger than those for the acid complexes by 9+/-1 kJ/mol, which is attributed
      to an inductive effect of the OH group in the carboxylic acid side chain.
      Additionally, the K(+) binding affinity for the longer-chain amino acids (Glx) is
      enhanced by 5+/-1 kJ/mol compared to the shorter-chain Asx because steric effects
      are reduced. Further, a detailed comparison between experimental and theoretical
      results reveals interesting differences in the binding of K(+) and Na(+) to these
      amino acids.

PMID- 18729511
TI  - Molecular engineering of organic sensitizers containing p-phenylene vinylene unit
      for dye-sensitized solar cells.
AB  - Three organic sensitizers containing bis-dimethylfluorenyl amino donor and a
      cyanoacrylic acid acceptor bridged by p-phenylene vinylene unit were synthesized.
      The power conversion efficiency was quite sensitive to the length of bridged
      phenylene vinylene groups. A nanocrystalline TiO2 dye-sensitized solar cell was
      fabricated using three sensitizers. The maximum power conversion efficiency of JK
      59 reached 7.02%.

PMID- 18729512
TI  - Arylthiols as highly chemoselective and environmentally benign radical reducing
      agents.
AB  - Arylthiols serve as excellent environmentally benign reducing agents for
      organotellurium, organostibine, and organobismuthine compounds under radical
      conditions. Both small molecules and macromolecules possessing these heteroatom
      groups are reduced under moderate thermal conditions to give near quantitative
      yields in most cases. The reduction shows high chemoselectivity with respect to
      the heteroatom compounds; the reactivity decreases in the order alkylbismuthines,
      alkylstibines, and alkyltellurides, while simple alkyl iodides could not be
      reduced. Alkyltellurides are selectively reduced in the presence of alkyl iodides
      even when an excess amount of arylthiol is used. Furthermore, alkylstibines are
      also selectively reduced in the presence of alkyltellurides. Moreover, the
      reduction conditions are compatible with the presence of a variety of polar
      functional groups in the substrates, products, and solvents, which are not
      tolerant under ionic and metal-catalyzed conditions. Carbon-carbon bond formation
      is possible with use of the carbon-centered radicals that are generated. The
      results clearly reveal the synthetic utility of arylthiols in organic synthesis.

PMID- 18729513
TI  - Block synthesis of tetra- and hexasaccharides (beta-D-glycero-D-manno-Hep p-(1-
      >4)-[alpha-l-Rha p-(1-->3)-beta-D-glycero-D-manno-Hep p-(1-->4)]n-alpha-L-Rha p
      OMe (n = 1 and 2)) corresponding to multiple repeat units of the glycan from the
      surface-layer glycoprotein from Bacillus thermoaerophilus.
AB  - A fully stereocontrolled block synthesis of the title tetra- and hexasaccharides
      has been achieved taking advantage of the ability of the 4,6-O-benzylidene acetal
      to control the stereochemistry of the beta-D-glycero-D-mannoheptopyranoside unit
      and of a 2,3-O-diphenylmethylene acetal to install the alpha-L-rhamnopyranosidic
      linkages. Comparison of the spectral data for the hexasaccharide with that of the
      natural isolate confirms the structure of this very unusual and structurally
      challenging glycan.

PMID- 18729514
TI  - Synthesis of neoglycoconjugates by the desulfurative rearrangement of allylic
      disulfides.
AB  - Two series of neoglycosyl donors are prepared on the basis of connection of an
      allylic disulfide motif to the anomeric center via a simple O-glycosyl linkage or
      N-glycosyl amide unit. Conjugation of both sets of donors to cysteine in peptides
      is demonstrated through classical disulfide exchange followed by the phosphine
      mediated desulfurative allylic rearrangement resulting in neoglycopeptides
      characterized by a simple thioether spacer. The conjugation reaction functions in
      the absence of protecting groups on both the neoglycosyl donor and peptide in
      aqueous media at room temperature.

PMID- 18729515
TI  - Dineopentyl phosphate hydrolysis: evidence for stepwise water attack.
AB  - Phosphate ester hydrolysis is ubiquitous in biology, playing a central role in
      energy production, signaling, biosynthesis, and the regulation of protein
      function among other things. Although the mechanism of action of the enzymes
      regulating this reaction has been the focus of intensive research in the past few
      decades, the correct description of this apparently simple reaction remains
      controversial. A clear understanding of the mechanism that takes place in
      solution is crucial to be able to evaluate whether proposals for the enzyme
      catalyzed mechanisms are reasonable. For the pH-independent hydrolysis of
      phosphate diesters, several kinetically equivalent mechanisms are plausible,
      including hydroxide attack on the neutral phosphate. However, it is very
      difficult to measure the rate of this reaction directly by experimental methods,
      so it has been evaluated by examining the rate of hydrolysis of neutral phosphate
      triesters, where a methyl group has replaced a proton. This may not be an
      accurate model of the neutral phosphate diester and does not provide information
      about a reaction pathway that is concerted with nucleophilic attack to generate a
      similar phosphorane. We have carefully mapped out free energy surfaces for both
      hydroxide and water attack on the dineopentyl phosphate anion and for water
      attack on the neutral diester. In doing so, we have accurately reproduced
      existing experimental data and demonstrate that water attack proceeds through an
      associative mechanism with proton transfer to the phosphate to generate a
      phosphorane intermediate. Our data show that the substrate-as-base mechanism is
      viable for phosphate ester hydrolysis, which may have important implications for
      the studies of phosphate ester hydrolysis by enzymes.

PMID- 18729516
TI  - Synthesis of zinc 3-hydroxymethyl-porphyrins possessing carbonyl groups at the 13
      and/or 15-positions for models of self-aggregative chlorophylls in green
      photosynthetic bacteria.
AB  - Zinc 3-hydroxymethyl-protopyropheophorbide-d derivatives 1, 2, and 3 possessing
      carbonyl group(s) at the 13/15-, 13-, and 15-positions, respectively, and 4
      lacking the C=O group were prepared from naturally occurring chlorophyll-a. Zinc
      porphyrins 1 and 2 possessing the 13-C=O self-aggregated in an aqueous micellar
      solution, similarly to the self-aggregates of BChls-c/d/e in the main light
      harvesting antenna systems of green photosynthetic bacteria, whereas 3 and 4
      lacking the 13-C=O failed to make such well-ordered aggregates. These results
      indicated that both the presence of the C=O group and its situation at the 13
      position were preferable for formation of the well-ordered J-aggregates.

PMID- 18729517
TI  - Antineoplastic agents. 552. Oxidation of combretastatin A-1: trapping the o
      quinone intermediate considered the metabolic product of the corresponding
      phosphate prodrug.
AB  - The very unstable (<10 min at rt) o-quinone 5 derived from the vicinal diphenol
      anticancer drug combretastatin A-1 (1) has been obtained by careful oxidation
      with NaIO4 and tetrabutylammonium bromide in water/dichloromethane. Immediate
      reaction with phenylenediamine (6) allowed o-quinone 5 to be trapped as the
      stable phenazine derivative 7. For further confirmation, 5 was also captured as a
      dimethoxyphenylenediamine-derived phenazine (11). Both phenazines 7 and 11
      significantly inhibited (ED50 approximately 0.2 microg/mL) growth of the murine
      P388 lymphocytic leukemia cell line and provided a new SAR insight in the
      combretastatin series of naturally occurring anticancer drugs.

PMID- 18729518
TI  - Ten-membered lactones from the marine-derived fungus Curvularia sp.
AB  - Investigation of the secondary metabolites of the marine-derived fungus
      Curvularia sp. yielded four new 10-membered lactones (1-4), along with the known
      modiolide A (5). The structures of 1-4 were characterized on the basis of
      spectroscopic and MS data and resemble known 10-membered lactones, but feature
      modified oxidation patterns around their macrocycles.

PMID- 18729519
TI  - Controlled/living radical polymerization in dispersed systems.

PMID- 18729520
TI  - The impact of nanocontact on nanowire based nanoelectronics.
AB  - Nanowire-based nanoelectronic devices will be innovative electronic building
      blocks from bottom up. The reduced nanocontact area of nanowire devices magnifies
      the contribution of contact electrical properties. Although a lot of two-contact
      based ZnO nanoelectronics have been demonstrated, the electrical properties
      bringing either from the nanocontacts or from the nanowires have not been
      considered yet. High quality ZnO nanowires with a small deviation and an average
      diameter of 38 nm were synthesized to fabricate more than thirty nanowire
      devices. According to temperature behaviors of current-voltage curves and
      resistances, the devices could be grouped into three types. Type I devices expose
      thermally activated transport in ZnO nanowires and they could be considered as
      two Ohmic nanocontacts of the Ti electrode contacting directly on the nanowire.
      For those nanowire devices having a high resistance at room temperatures, they
      can be fitted accurately with the thermionic-emission theory and classified into
      type II and III devices according to their rectifying and symmetrical current
      voltage behaviors. The type II device has only one deteriorated nanocontact and
      the other one Ohmic contact on single ZnO nanowire. An insulating oxide layer
      with thickness less than 20 nm should be introduced to describe electron hopping
      in the nanocontacts, so as to signalize one- and high-dimensional hopping
      conduction in type II and III devices.

PMID- 18729521
TI  - Copolymer-cyclodextrin inclusion complexes in water and in the solid state. A
      physico-chemical study.
AB  - The formation of inclusion complexes (ICs) composed of cyclodextrins (CDs) and
      poly(ethylene oxides)-poly(propylene oxides)-poly(ethylene oxides) (PEO-PPO-PEO)
      was studied. To this purpose, native and hydroxypropyl cyclodextrins with
      different cavity size were chosen. The PEO-PPO-PEO copolymers were selected to
      study the role of the molecular weight, keeping constant the
      hydrophilic/hydrophobic ratio, and the hydrophilicity. The volumetric studies at
      25 degrees C allowed to determine the equilibrium constant and the volume change
      for the IC formation in water as well as the IC stoichiometry. Surface tension
      experiments evidenced that the copolymer and the CD interfacial behavior is
      controlled by the formation of ICs taking place in the bulk phase. It was proved
      that the differential scanning calorimetry (DSC) is a valid method to describe
      quantitatively the IC in the solid state. The combination of volumes, DSC and
      FTIR techniques together with the geometric information highlighted the following
      points: (1) the included copolymer is in the amorphous state; (2) the IC composed
      of native CDs adopts a channel structure with two EO units incorporated into one
      CD molecule; (3) the IC composed of hydroxypropyl-cyclodextrin is a polymeric
      structure like a necklace decorated with CD rings. Finally, TGA experiments
      showed that the thermal stability of the IC depends on the nature of both
      components.

PMID- 18729524
TI  - Solid-phase synthesis of difficult peptide sequences at elevated temperatures: a
      critical comparison of microwave and conventional heating technologies.
AB  - The Fmoc/t-Bu solid-phase synthesis of three difficult peptide sequences (a 9
      mer, 15-mer, and 24-mer) was performed using N,N'-diisopropylcarbodiimide/1
      hydroxybenzotriazole as coupling reagent on polystyrene, Tentagel, and ChemMatrix
      resins. In order to obtain an insight into the specific role of the elevated
      temperature and/or the electromagnetic field for peptide syntheses carried out
      using microwave irradiation, peptide couplings and Fmoc-deprotection steps were
      studied under microwave and conventionally heated conditions at the same
      temperature. While room temperature couplings/deprotections generally produced
      the difficult peptides in rather poor quality, excellent peptide purities were
      obtained using microwave heating at a temperature of 86 degrees C for both the
      coupling and deprotection steps in only 10 and 2.5 min reaction time,
      respectively. While for most amino acids no significant racemization was
      observed, the high coupling temperatures led to considerable levels of
      racemization for the sensitive amino acids His and Cys. It was demonstrated for
      all three peptide sequences that when performing the coupling/deprotection steps
      at the same reaction temperature using conventional heating, nearly identical
      results in terms of both peptide purity and racemization levels were obtained. It
      therefore appears that the main effect of microwave irradiation applied to solid
      phase peptide synthesis is a purely thermal effect not related to the
      electromagnetic field.

PMID- 18729525
TI  - Phosphine-free palladium(II)-catalyzed arylation of naphthalene and benzene with
      aryl iodides.
AB  - A phosphine-free arylation of naphthalene and benzene with aryl iodides to give
      biaryls in moderate to good yields is carried out in the presence of catalytic
      Pd(OAc)2 and stoichiometric CF3CO2 Ag in TFE or/and TFA.

PMID- 18729522
TI  - NMR, mass spectrometry and chemical evidence reveal a different chemical
      structure for methanobactin that contains oxazolone rings.
AB  - Methanobactin (mb) is a small copper-binding peptide produced by methanotrophic
      bacteria and is intimately involved in both their copper metabolism and their
      role in the global carbon cycle. The structure for methanobactin comprises seven
      amino acids plus two chromophoric residues that appear unique to methanobactin.
      In a previously published structure, both chromophoric residues contain a
      thiocarbonyl attached to a hydroxyimidazolate ring. In addition, one is attached
      to a pyrrolidine ring, while the other is attached to an isopropyl ester. A
      published X-ray determined structure for methanobactin shows these two
      chromophoric groups forming an N2S2 binding site for a single Cu(I) ion with a
      distorted tetrahedral geometry. In this report we show that NMR, mass
      spectrometry, and chemical data reveal a chemical structure that is significantly
      different than the previously published one. Specifically, the 1H and 13C NMR
      assignments are inconsistent with an N-terminal isopropyl ester and point instead
      to a 3-methylbutanoyl group. Our data also indicate that oxazolone rings instead
      of hydroxyimidazolate rings form the core of the two chromophoric residues.
      Because these rings are directly involved in the binding of Cu(I) and other
      metals by methanobactin and are likely involved in the many chemical activities
      displayed by methanobactin, their correct identity is central to developing an
      accurate and detailed understanding of methanobactin's many chemical and
      biological roles. For example, the oxazolone rings make methanobactin
      structurally more similar to other bacterially produced bactins and siderophores
      and suggest pathways for its biosynthesis.

PMID- 18729526
TI  - Conformational domino effect in saccharides. 2. Anomeric configuration control.
AB  - A series of alkyl beta-D-glucopyranosyl-(1-->6)-alpha-D-glucopyranosides were
      synthesized and analyzed by NMR and CD techniques. As in their beta-anomer
      series, the rotational populations of the hydroxymethyl group involved in the
      interglycosidic linkage (torsion angle omega) are shown to depend on the aglycon
      and the solvent. However, for this alpha-anomer series the rotational dependence
      arises directly from steric effects. Correlations between rotational populations
      and molar refractivity (MR) steric parameters, but not Taft's steric parameters
      (beta-anomers), of the alkyl substituents were observed. The conformational
      domino effect previously predicted from alkyl beta-(1-->6)-diglucopyranosides is
      now supported by the conformational properties of their alpha-anomers, the
      anomeric configuration controlling the domino effect. In addition, the rotational
      populations around the C5'-C6' bond (torsion angle omega') depend weakly on the
      structure of the aglycon and the anomeric configuration.

PMID- 18729527
TI  - Water-soluble conjugated polymer-induced self-assembly of gold nanoparticles and
      its application to SERS.
AB  - Gold nanochains were prepared by the assembly of citrate-stabilized gold
      nanospheres induced by cationic conjugated polymers. This assembly method was
      rapid, and the assembled product was very stable. A longitudinal plasmon
      resonance band was formed as a result of the coupling of gold nanoparticles and
      can be tuned from visible to near-infrared by adjusting the polymer/Au molar
      ratio. The gold nanochains were used as a SERS substrate and gave an enhancement
      factor of 8.4 x 10 (9), which is approximately 400 times larger than that on the
      isolated gold nanosphere substrate. The giant SERS enhancement is ascribed to the
      large electromagnetic fields of coupled gold nanoparticles.

PMID- 18729528
TI  - Poly(ethylene glycol) monolayer formation and stability on gold and silicon
      nitride substrates.
AB  - Poly(ethylene glycol) (PEG) self-assembled monolayers (SAMs) are extensively used
      to modify substrates to prevent nonspecific protein adsorption and to increase
      hydrophilicity. X-ray photoelectron spectroscopy analysis, complemented by water
      contact angle measurements, is employed to investigate the formation and
      stability upon aging and heating of PEG monolayers formed on gold and silicon
      nitride substrates. In particular, thiolated PEG monolayers on gold, with and
      without the addition of an undecylic spacer chain, and PEG monolayers formed with
      oxysilane precursors on silicon nitride have been probed. It is found that PEG
      thiol SAMs are degraded after less than two weeks of exposure to air and when
      heated at temperatures as low as 120 degrees C. On the contrary, PEG-silane SAMs
      are stable for more than two weeks, and fewer molecules are desorbed even after
      two months of aging, compared to those desorbed in two weeks from the PEG-thiol
      SAMs. A strongly bound hydration layer is found on PEG-silane SAMs aged for two
      months. Heating PEG-silane SAMs to temperatures as high as 160 degrees C improves
      the quality of the monolayer, desorbing weakly bound contaminants. The
      differences in stability between PEG-thiol SAMs and PEG-silane SAMs are ascribed
      to the different types of bonding to the surface and to the fact that the thiol
      Au bond can be easily oxidized, thus causing desorption of PEG molecules from the
      surface.

PMID- 18729529
TI  - New development in processing pendant droplet tensiometry data.
AB  - A database linking the dimensionless volume of pendant droplets Vpen and the
      dimensionless volume of the spherical caps at the apex of the droplets Vcap has
      been constructed from the governing equations of pendant droplet tensiometry. The
      Bond number Bo that relates surface tension to gravitational body force appears
      as an independent parameter in this database. Computing Vpen and Vcap from the
      measured profile of a droplet and making use of the database allow the prevailing
      Bo to be determined and surface tension to be calculated. This new way of
      converting measured profiles into surface tension has a number of advantages,
      such as reliability and simplicity, compared to existing methods. These are
      demonstrated by applying the new method to a number of measured profile data
      taken from the literature.

PMID- 18729530
TI  - Cross-linked polynorbornene-coated gold nanoparticles: dependence of particle
      stability on cross-linking position and cross-linker structure.
AB  - This paper describes the preparation of cross-linked polynorbornene coated gold
      nanoparticles. The polymer was grown radially from the particle surface using a
      ring opening metathesis polymerization of norbornene and an electrophilic
      norbornene ester, which was cross-linked using a variety of diamines. The
      stability of the cross-linked nanoparticles toward oxidative etching by cyanide
      was evaluated. The rate of etching decreases as diamines with fewer degrees of
      conformational freedom are used as cross-linkers. The distance of the cross
      linking block from the nanoparticle surface was systematically varied.
      Nanoparticles with the cross-linked block furthest from the surface were etched
      most slowly. This is suggested to arise as a result of the polymers adopting a
      mushroom conformation when the cross-linking block is close to the particle
      surface, while more distal cross-linking results in more rigid polymer chains
      that are less permeable to the cyanide etchant. These results provide new insight
      into how fine-tuning the polymer cross-linking architecture can modulate
      nanoparticle stability.

PMID- 18729531
TI  - Structure of microemulsion-ABA triblock copolymer networks.
AB  - Structural equilibrium properties of transient networks formed by microemulsion
      droplets and ABA triblock copolymers in solution have been studied by Monte Carlo
      simulation. The droplets were represented by soft spheres, and the polymers were
      represented by junctions connected by harmonic bonds with an angular potential
      regulating the intrinsic chain stiffness. The interaction parameters were
      selected such that the end A-blocks were localized inside the droplets and the
      middle B-block in the continuous phase. The influence of (i) the polymer
      concentration, (ii) the polymer stiffness, and (iii) the contour length of the
      middle B-block on the formation and the structure of the microemulsion-polymer
      network were investigated using polymer end-to-end separation probability
      distribution functions, droplet radial distribution functions, droplet-droplet
      nearest-neighbor probability distribution functions, and network connectivity
      indicators. An increase of the polymer-droplet number ratio had a strong impact
      on the network formation. Under typical conditions and at an intermediate polymer
      droplet number ratio, (i) the fraction of polymers forming bridges between
      droplets increased from essentially zero to unity and (ii) the fraction of
      polymers that were forming loops decreased as the ratio of the polymer end-to-end
      separation and the surface-to-surface separation between neighboring droplets for
      a hypothetical homogeneous droplet distribution was increased from 0.5 to 2. For
      long and flexible polymers, a mesoscopic segregation triggered by a depletion
      attraction between droplets appeared, and, furthermore, for sufficiently stiff
      chains, only bridge conformations occurred. The percolation probability could be
      represented as a function of the average droplet cluster size only, across all
      systems.

PMID- 18729532
TI  - HMG-CoA reductase inhibitors: do they have potential in the treatment of
      polycystic ovary syndrome?
AB  - Many women of reproductive age are affected by polycystic ovary syndrome (PCOS),
      a heterogeneous endocrinopathy characterized by androgen excess, chronic oligo
      anovulation and/or polycystic ovarian morphology. In addition, PCOS is often
      associated with insulin resistance, systemic inflammation and oxidative stress,
      which, on one hand, lead to endothelial dysfunction and dyslipidaemia with
      subsequent cardiovascular sequelae and, on the other hand, to hyperplasia of the
      ovarian theca compartment with resultant hyperandrogenism and anovulation.
      Traditionally, HMG-CoA reductase inhibitors (statins) have been used to treat
      dyslipidaemia by blocking HMG-CoA reductase (the rate-limiting step in
      cholesterol biosynthesis); however, they also possess pleiotropic actions,
      resulting in antioxidant, anti-inflammatory and anti-proliferative effects.
      Statins offer a novel therapeutic approach to PCOS in that they address the
      dyslipidaemia associated with the syndrome, as well as hyperandrogenism or
      hyperandrogenaemia. These actions may be due to an inhibition of the effects of
      systemic inflammation and insulin resistance/hyperinsulinaemia. Evidence to date,
      both in vitro and in vivo, suggests that statins have potential in the treatment
      of PCOS; however, further clinical trials are needed before they can be
      considered a standard of care in the medical management of this common
      endocrinopathy.

PMID- 18729533
TI  - Local treatment of vulvovaginal candidosis : general and practical
      considerations.
AB  - Vulvovaginal candidosis is a common worldwide female medical problem, occurring
      mostly in women of childbearing age. Currently available options for the
      treatment of this condition include local and oral (systemic) therapy. Both
      alternatives have been considered equally effective in the treatment of
      uncomplicated vulvovaginal candidosis, although oral regimens are often preferred
      by physicians and women. However, local treatment presents several advantageous
      and unique features that may favour this therapeutic approach. The availability
      of numerous antifungal drugs and products for topical administration makes the
      selection quite challenging as this task is mostly based on personal experience
      or anecdotal data. Also, recent advances have been made in topical antifungal
      formulations and there is an increasing availability of over-the-counter
      products. Therefore, a review of both general and practical considerations
      related to the local treatment of vulvovaginal candidosis is timely.In summary,
      azoles and short-term regimens are usually recommended for the local treatment of
      vulvovaginal candidosis, with nystatin and boric acid considered as second-line
      alternatives. Unconventional approaches may also be regarded as suitable in
      patients refractory to usual treatments. In addition to the susceptibility of
      implicated Candida spp. to the antifungal agents, this choice should take into
      consideration other important issues such as particular situations (e.g.
      pregnancy, menopause, drug hypersensitivity), women's preferences, and the
      availability, particularities and cost of antifungal formulations.

PMID- 18729535
TI  - Short- versus long-course antibacterial therapy for community-acquired pneumonia
      : a meta-analysis.
AB  - BACKGROUND: The evidence for traditionally recommended 7- to 14-day duration of
      antibacterial therapy for community-acquired pneumonia (CAP) is not well
      established. OBJECTIVES: We endeavoured to assess the effectiveness and safety of
      shorter than traditionally recommended antibacterial therapy for CAP. METHODS: We
      performed a meta-analysis of randomized controlled trials (RCTs) comparing short-
      (< or = 7 days) versus long- (> or = 2 days difference) course therapy for CAP
      with the same antibacterial regimens, in the same daily dosages. RESULTS: Five
      RCTs involving adults (including outpatients and inpatients who did not require
      intensive care) and two RCTs involving children (aged 2-59 months, residing in
      developing countries) were included. All RCTs were double-blind and assessed
      patients with CAP of mild to moderate severity. No differences were found between
      short- (adults 3-7 days; children 3 days) and long- (adults 7-10 days; children 5
      days) course regimens (adults - amoxicillin, cefuroxime, ceftriaxone,
      telithromycin and gemifloxacin; children - amoxicillin) regarding clinical
      success at end-of-therapy (six RCTs; 5107 patients [1095 adults, 4012 children];
      fixed-effect model [FEM]; odds ratio [OR] = 0.89; 95% CI 0.74, 1.07), clinical
      success at late follow-up, microbiological success, relapses, mortality (seven
      RCTs; 5438 patients; FEM; OR = 0.57; 95% CI 0.23, 1.43), adverse events (five
      RCTs; 3214 patients; FEM; OR = 0. 90; 95% CI 0.72, 1.13) or withdrawals as a
      result of adverse events. No differences were found in subset analyses of adults
      or children, and of patients treated with no more than 5-day short-course
      regimens versus at least 7-day long-course regimens. CONCLUSION: No difference
      was found in the effectiveness and safety of short- versus long-course
      antimicrobial treatment of adult and paediatric patients with CAP of mild to
      moderate severity.

PMID- 18729536
TI  - Budesonide/Formoterol pressurized metered-dose inhaler.
AB  - *The corticosteroid budesonide and the long-acting [beta]2-adrenoceptor agonist
      formoterol have been combined into a single pressurized metered-dose inhaler
      (pMDI) for use in patients aged > or =12 years with asthma. *In well designed 12
      week clinical trials in patients with mild to moderate or moderate to severe
      persistent asthma, lung function improved to a significantly greater extent with
      twice-daily budesonide/formoterol pMDI 160 [micro]g/9 [micro]g or 320 [micro]g/9
      [micro]g than with placebo or the same nominal dosage of either of the components
      alone. *Budesonide/formoterol pMDI was also associated with improvements from
      baseline in patient-reported asthma control, asthma symptom and asthma-related
      quality of life outcomes that were significantly greater than those with placebo
      and, for many endpoints, monotherapy with the individual components. *In a 52
      week safety study, treatment with twice-daily budesonide/formoterol pMDI 320
      [micro]g/9 [micro]g was associated with rapid and durable improvements in lung
      function and asthma control that were significantly greater than those with twice
      daily budesonide pMDI 640 [micro]g monotherapy. *Budesonide/formoterol pMDI was
      well tolerated in clinical trials. Its overall adverse event profile is
      consistent with the known tolerability profiles of long-acting [beta]2
      adrenoceptor agonist and inhaled corticosteroid therapy, and is similar to that
      shown with placebo.

PMID- 18729534
TI  - Approved and investigational uses of modafinil : an evidence-based review.
AB  - Modafinil is a wake-promoting agent that is pharmacologically different from
      other stimulants. It has been investigated in healthy volunteers, and in
      individuals with clinical disorders associated with excessive sleepiness,
      fatigue, impaired cognition and other symptoms. This review examines the use of
      modafinil in clinical practice based on the results of randomized, double-blind,
      placebo-controlled clinical trials available in the English language in the
      MEDLINE database. In sleep-deprived individuals, modafinil improves mood,
      fatigue, sleepiness and cognition to a similar extent as caffeine but has a
      longer duration of action. Evidence for improved cognition in non-sleep-deprived
      healthy volunteers is controversial.Modafinil improves excessive sleepiness and
      illness severity in all three disorders for which it has been approved by the US
      FDA, i.e. narcolepsy, shift-work sleep disorder and obstructive sleep apnoea with
      residual excessive sleepiness despite optimal use of continuous positive airway
      pressure (CPAP). However, its effects on safety on the job and on morbidities
      associated with these disorders have not been ascertained. Continued use of CPAP
      in obstructive sleep apnoea is essential. Modafinil does not benefit cataplexy.In
      very small, short-term trials, modafinil improved excessive sleepiness in
      patients with myotonic dystrophy. It was efficacious in fairly large studies of
      attention deficit hyperactivity disorder (ADHD) in children and adolescents, and
      was as efficacious as methylphenidate in a small trial, but has not been approved
      by the FDA, in part because of its serious dermatological toxicity. In a trial of
      21 non-concurrent subjects, with 2-week treatment periods, modafinil was as
      effective as dexamfetamine in adult ADHD. Modafinil was helpful for depressive
      symptoms in bipolar disorder in a trial that excluded patients with stimulant
      induced mania. A single dose of modafinil may hasten recovery from general
      anaesthesia after day surgery. A single dose of modafinil improved the ability of
      emergency room physicians to attend didactic lectures after a night shift, but
      did not improve their ability to drive home and caused sleep disturbances
      subsequently.Modafinil had a substantial placebo effect on outcomes such as
      fatigue, excessive sleepiness and depression in patients with traumatic brain
      injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple
      sclerosis; however, it did not provide any benefit greater than placebo.Trials of
      modafinil for excessive sleepiness in Parkinson's disease, cocaine addiction and
      cognition in chronic fatigue syndrome provided inconsistent results; all studies
      had extremely small sample sizes. Modafinil cannot be recommended for these
      conditions until definitive data become available.Modafinil induces and inhibits
      several cytochrome P450 isoenzymes and has the potential for interacting with
      drugs from all classes. The modafinil dose should be reduced in the elderly and
      in patients with hepatic disease. Caution is needed in patients with severe renal
      insufficiency because of substantial increases in levels of modafinil acid.
      Common adverse events with modafinil include insomnia, headache, nausea,
      nervousness and hypertension. Decreased appetite, weight loss and serious
      dermatological have been reported with greater frequency in children and
      adolescents, probably due to the higher doses (based on bodyweight) used.
      Modafinil may have some abuse/addictive potential although no cases have been
      reported to date.

PMID- 18729537
TI  - Febuxostat.
AB  - *Febuxostat is an orally administered, non-purine, selective inhibitor of
      xanthine oxidase approved for the management of chronic hyperuricaemia in
      patients with gout. *In a randomized, double-blind, dose-ranging study in
      patients with gout and hyperuricaemia, significantly more recipients of
      febuxostat 40-120 mg/day than placebo had serum urate levels of < 6.0 mg/dL after
      4 weeks of treatment. *Serum urate levels were reduced below 6.0 mg/dL at the
      last three monthly observations in a significantly greater proportion of patients
      with gout and hyperuricaemia receiving febuxostat 80 or 120 mg once daily than in
      those receiving allopurinol 300 mg once daily in a 52-week, randomized, double
      blind trial (FACT). *Similarly, febuxostat 80, 120 or 240 mg once daily showed
      significantly greater urate-lowering efficacy than allopurinol 100 or 300 mg once
      daily in a 28-week, randomized, double-blind, placebo-controlled trial (APEX) in
      patients with gout and hyperuricaemia. *Long-term treatment with febuxostat for
      up to 4 years or more reduced the incidence of gout flares to (or close to) zero.
      *Febuxostat was generally well tolerated in clinical trials, including extension
      studies lasting > or = 4 years, with most treatment-related adverse events being
      mild to moderate in severity.

PMID- 18729538
TI  - Febuxostat: a viewpoint by H. Ralph Schumacher Jr and Lan X. Chen.

PMID- 18729539
TI  - Febuxostat : a viewpoint by Naomi Schlesinger.

PMID- 18729540
TI  - Febuxostat : a viewpoint by N. Lawrence Edwards.

PMID- 18729541
TI  - Telmisartan/Hydrochlorothiazide: a review of its use as fixed-dose combinations
      in essential hypertension.
AB  - Fixed-dose combinations of telmisartan and hydrochlorothiazide (HCTZ) [Micardis
      Plus, Micardis HCT, PritorPlus] are available in many countries for the treatment
      of patients with essential hypertension. Combining the angiotensin II receptor
      antagonist (angiotensin II receptor blocker [ARB]) telmisartan with the thiazide
      diuretic HCTZ provides antihypertensive therapy with complementary mechanisms of
      action. In the US and EU, telmisartan/HCTZ is approved for patients whose
      hypertension is not adequately controlled with telmisartan monotherapy; US
      labelling for the fixed-dose combination also includes inadequate control of
      blood pressure (BP) with HCTZ monotherapy.The antihypertensive efficacy of once
      daily telmisartan/HCTZ has been demonstrated in several large, randomized trials
      in patients with stages 1 and 2 hypertension. The addition of HCTZ to telmisartan
      achieved significant reductions in BP in nonresponders to telmisartan
      monotherapy, and the antihypertensive efficacy of telmisartan/HCTZ was similar to
      or significantly greater than that of various comparator agents. Moreover, in
      studies that used ambulatory BP monitoring, telmisartan/HCTZ provided consistent
      24-hour BP reductions throughout morning, daytime and night-time periods. The BP
      lowering efficacy over the entire 24-hour dose administration interval is
      consistent with the pharmacokinetic profile of telmisartan, which has the longest
      elimination half-life among currently available ARBs and a unique chemical
      structure. Adverse events with telmisartan/HCTZ in clinical trials were typically
      mild and transient, and no unexpected events occurred that had not been
      previously reported with either telmisartan or HCTZ. Extensive tolerability data
      are available for telmisartan, in particular from the ONTARGET study, the largest
      clinical outcomes trial with an ARB. As such, fixed-dose combinations of
      telmisartan/HCTZ provide an effective, rational and generally well tolerated
      treatment option for the management of patients with hypertension.

PMID- 18729542
TI  - Ramelteon: a review of its use in insomnia.
AB  - Ramelteon (Rozerem) is the first melatonin receptor agonist to be approved for
      the treatment of insomnia; it is not classified as a controlled substance. In
      patients with chronic insomnia, objectively assessed latency to persistent sleep
      (LPS) at week 1 was improved with oral ramelteon 8 mg administered 30 minutes
      before bedtime, compared with placebo, and this effect was maintained throughout
      the duration of 5-week and 6-month clinical studies. Subjectively assessed sleep
      latency (sSL) improved in some, but not all, studies. When a statistically
      significant improvement in sSL occurred at week 1, the effect was maintained
      throughout the duration of the 5-week studies, but not at all timepoints
      throughout a 6-month study. Improvements in objectively assessed total sleep time
      (TST) and sleep efficiency (SE) were only reported during the first week of
      treatment. Improvements in other objective or subjective measures of sleep were
      not consistent. Ramelteon was generally well tolerated, did not impair next-day
      cognitive or motor performance and was not associated with withdrawal symptoms,
      rebound insomnia or abuse potential. Thus, ramelteon provides a well tolerated
      option for the treatment of patients with insomnia characterized by difficulty in
      sleep onset.

PMID- 18729543
TI  - Anaesthetic drugs and defibrillation threshold testing.

PMID- 18729545
TI  - What defines abnormal lung function in older adults with chronic obstructive
      pulmonary disease?
AB  - Chronic obstructive pulmonary disease (COPD) is a very common lung disease most
      often related to a history of smoking. It becomes more prevalent with increasing
      age but remains under-diagnosed and under-treated in the elderly population. The
      Global Initiative for Obstructive Lung Disease (GOLD) programme has been
      instrumental in providing standard diagnostic criteria as well as recommendations
      for prevention and management of COPD. GOLD recommendations define COPD as a post
      bronchodilator forced expiratory volume in 1 second (FEV(1))/forced vital
      capacity (FVC) of <70%, with the severity based on the value of FEV(1). This
      recommendation is different from that of many previous reports that have
      recommended diagnosing obstruction using the statistically derived lower limit of
      normal (LLN), which varies for each person according to age, height, ethnicity
      and gender. While the use of a 70% ratio may be simpler, it may result in under
      diagnosis of airflow obstruction in younger people and over-diagnosis in the
      elderly. This is particularly important as the elderly may be most sensitive to
      many of the adverse effects of medications used in the treatment of COPD,
      including corticosteroids and anticholinergic bronchodilators.Most of the studies
      comparing the LLN and a fixed ratio of 70% have not been performed with post
      bronchodilator testing as recommended by GOLD. Generation of post-bronchodilator
      reference sets and studies comparing the LLN with the post-bronchodilator
      FEV(1)/FVC ratio of <70% will help resolve this issue. One recent study examined
      patients admitted to hospitals who had an FEV(1)/FVC ratio of <70% but above the
      LLN, and found they were at increased risk of death and COPD complications. This
      would support the use of GOLD criteria. Further studies examining this population
      are needed.In addition to the uncertainties about what diagnostic criteria should
      be utilized for diagnosis of airflow obstruction, different organizations make
      different recommendations on screening spirometry. A conservative recommendation
      is to perform spirometry in symptomatic individuals. It is important to remember
      that while COPD is under-diagnosed in the elderly, this group is also at a higher
      risk of being falsely classified as having airflow obstruction using the 70%
      ratio recommended by GOLD. This can result in unnecessary use of medications and
      increased risk of adverse effects to which the elderly are more prone.

PMID- 18729546
TI  - Pharmacological management of primary open-angle glaucoma: second-line options
      and beyond.
AB  - Glaucoma is one of the leading causes of blindness worldwide. Increased
      intraocular pressure (IOP) is considered to be the most important risk factor.
      Major outcome studies from recent years have shown that lowering IOP is
      beneficial in primary open-angle glaucoma and ocular hypertension. The
      introduction of new classes of IOP-lowering drugs (alpha(2)-adrenoceptor
      agonists, topical carbonic anhydrase inhibitors and hypotensive lipids) in the
      last decade has contributed to a change in the drug prescription pattern.
      Together with beta-adrenoceptor antagonists (beta-blockers), these drugs are now
      considered to be first-choice classes, giving ophthalmologists ample
      opportunities to choose from a broad spectrum of IOP-lowering drugs. The number
      of possible medical treatment combinations has increased likewise.We review
      medical treatment combinations of two, three or four drugs from the four major
      first-choice glaucoma drug classes and provide an overview of the scientific
      evidence for IOP efficacy of second-line medical options when first-line therapy
      has been effective but additional IOP lowering is necessary. A systematic search
      of the literature initially revealed 2729 publications. After a thorough
      selection process, 42 studies were found to be eligible for inclusion in the
      review. Publications were excluded if the primary endpoint of the study was not
      IOP or if glaucoma topics other than IOP lowering of drugs were studied. In
      addition, studies that reported results for monotherapies only were excluded. The
      vast majority of study arms reported on combinations of a beta-blocker with
      either a carbonic anhydrase inhibitor or a hypotensive lipid. For a number of
      treatment combinations no eligible studies were available or could be
      included.This review shows that combining drugs from the different first-choice
      classes results in an additional IOP decrease. The exact magnitude of this
      additional decrease and the patients to whom it applies remain unclear. In many
      studies, no information on IOP before the run-in phase was available. However,
      such data are important in order to determine whether patients with high
      untreated IOP or patients non-responsive to the run-in drug(s) were
      preferentially included. Another issue that hampers interpretation is the fact
      that the timepoints of measurements of IOP before and after adding a drug should
      be related to the peak and trough times of the drugs. Finally, differences
      between concomitant use and fixed combined use of drugs may have consequences for
      the interpretation of results.

PMID- 18729547
TI  - Transdermal delivery of treatment for Alzheimer's disease: development, clinical
      performance and future prospects.
AB  - There is increasing interest in the potential of transdermal drug delivery
      systems for the treatment of neurological disorders, especially in the elderly.
      In this population, the higher incidence of chronic diseases, such as diabetes
      mellitus, cardiovascular disease, neurological disease and chronic pain, has
      dramatically increased the need for long-term medications. Additionally, elderly
      patients often have a combination of several chronic diseases, meaning drug
      delivery, drug-drug interactions, absorption/blood concentrations, toxicity and
      compliance are of concern for patients as well as for their caregivers and
      physicians. Recent efforts have focused on developing pharmaceutical preparations
      that overcome these issues. For example, rate-controlled drug delivery systems
      have been under active development. Transdermal drug delivery systems have been
      developed to deliver phenserine, rivastigmine, nicotine and estradiol for the
      management of cognitive and behavioural dysfunctions in patients with Alzheimer's
      disease because this form of administration has several advantages, including
      maintenance of sustained therapeutic plasma concentrations of drugs, easy
      application and reduced systemic adverse effects. Thus, transdermal drug delivery
      for elderly patients offers promise as the ideal therapeutic approach to treating
      Alzheimer's disease.This article reviews the technical principles underlying the
      development of transdermal drug delivery systems, focusing on cholinesterase
      inhibitors, and the prospects for future development. The clinical performance of
      transdermal patches, again with emphasis on cholinesterase inhibitors, is also
      reviewed.

PMID- 18729548
TI  - Inappropriate medication use and prescribing indicators in elderly Australians:
      development of a prescribing indicators tool.
AB  - BACKGROUND: Evidence-practice gaps, adverse medication-related incidents and
      unplanned medical admissions to hospital are common in elderly Australians. Many
      prescribing indicator tools designed to address some of these problems have been
      reported in the literature, the most common of which is the Beers list of
      inappropriate medications in the elderly. However, many of these tools are not
      appropriate for the Australian healthcare environment without modification and
      validation, and there appears to be a need for a tool based on Australian data.
      OBJECTIVE: To develop a list of prescribing indicators for elderly (aged >65
      years) Australians based on the most frequent medications prescribed to
      Australians, and the most frequent medical conditions for which elderly
      Australians consult medical practitioners. METHOD: The most common reasons for
      elderly Australians to seek or receive healthcare were cross-referenced with the
      50 highest-volume Pharmaceutical Benefits Scheme medications prescribed to
      Australians in 2006 to develop prescribing indicators in the elderly using
      Australian medication and medical condition information resources. RESULTS: Forty
      eight prescribing indicators were identified, consisting mainly of optimum as
      well as inappropriate medication choices for a large number of common medical
      conditions in the elderly. CONCLUSION: A prescribing indicators tool was
      developed. This tool is envisaged as forming an important part of the medication
      review process, which is aimed at addressing the common problem of adverse
      medication-related events in elderly Australians.

PMID- 18729550
TI  - The chimney graft: a technique for preserving or rescuing aortic branch vessels
      in stent-graft sealing zones.
AB  - PURPOSE: To report an alternative to the fenestrated stent-graft for preserving
      blood flow to side branches in the sealing zones of aortic stent-grafts.
      TECHNIQUE: A covered stent is deployed parallel to the main aortic stent-graft,
      protruding somewhat proximally, like a chimney, to preserve flow to a vital side
      branch covered by the aortic stent-graft. Use of a chimney graft makes it
      possible to use standard off-the-shelf stent-grafts to instantly treat lesions
      with inadequate fixation zones, providing an alternative to fenestrated stent
      grafts in urgent cases, in aneurysms with challenging neck morphology, and for
      reconstituting an aortic side branch unintentionally compromised during
      endovascular repair. This technique has been used successfully in 10 patients,
      combining chimney grafts in the renal, superior mesenteric, left subclavian, left
      common carotid, and innominate arteries with stent-grafts in the abdominal (n=6)
      or thoracic (n=4) aorta. There has been no late chimney graft-related endoleak on
      imaging studies up to 8 months. CONCLUSION: The use of chimney grafts is feasible
      in the renal and superior mesenteric arteries, as well as in the supra-aortic
      branches, to facilitate stent-graft repair of thoracic or abdominal aortic
      lesions with inadequate fixation zones.

PMID- 18729549
TI  - Association between depressive symptoms and use of HMG-CoA reductase inhibitors
      (statins), corticosteroids and histamine H(2) receptor antagonists in community
      dwelling older persons: cross-sectional analysis of a population-based cohort.
AB  - BACKGROUND: Strong evidence supporting the existence of causal associations of
      drug use with depression is often lacking from empirical studies. Limited
      evidence suggests an inverse association of use of HMG-CoA reductase inhibitors
      (statins) with depressive symptoms. Sparse and sometimes conflicting data in this
      respect have also been reported for corticosteroids, histamine H(2) receptor
      antagonists and antihypertensive agents. OBJECTIVE: To identify associations
      between use of different drug classes and depressive symptoms in community
      dwelling older patients and to determine whether any such associations varied
      between young-old and old-old patients. METHOD: We analysed cross-sectional data
      from a population-based cohort of 2804 older adults aged > or =55 years, in whom
      specific drug use was systematically identified from self-reports and physical
      inspection of medication labels. Depressive symptoms were determined using the 15
      item Geriatric Depression Scale (GDS), with a GDS score > or =5 defining the
      presence of depressive symptoms. RESULTS: Multivariate analysis controlling for
      the confounding effects of risk factors and correlates of depression revealed
      significant associations between depressive symptoms and use of statins (odds
      ratio [OR] 0.71; 95% CI 0.52, 0.97), histamine H(2) receptor antagonists for
      patients aged <65 years (OR 4.67; 95% CI 1.59, 13.74) and, in participants aged >
      or =65 years, systemic corticosteroids (OR 4.02; 95% CI 1.12, 14.42). No
      convincing associations between the presence of depressive symptoms and use of
      antihypertensives, antiparkinsonism drugs, NSAIDs and
      tranquilizers/hypnotic/sedatives were demonstrated. CONCLUSION: The evidence in
      this study suggests a possible protective effect of statin use on depressive
      symptoms, and affirms a positive association between depressive symptoms and
      corticosteroid use, especially in the older elderly. Use of H(2) receptor
      antagonists was also associated with depressive symptoms, probably through their
      link with underlying dyspeptic syndromes.

PMID- 18729551
TI  - Open decompression, proximal banding, and aneurysm sac fenestration as an
      alternative to conversion in the management of endotension after EVAR.
AB  - PURPOSE: To present a technique to treat endotension and avoid surgical
      conversion after endovascular aneurysm repair (EVAR). TECHNIQUE: The surgical
      procedure is based on decompression, downsizing, and fenestration of the aneurysm
      sac combined with proximal aortic neck banding and transmural endograft fixation
      with sutures. Among 193 patients who underwent infrarenal EVAR between October
      2001 and October 2007, 3 (1.5%) patients developed endotension without evidence
      of endoleak (increasing aneurysm diameter in 2 and a pulsating aneurysm with
      unchanged diameter in the third). This technique was applied successfully in
      uneventful procedures. Considerable shrinkage of the aneurysm sac has been
      observed over a 13- to 31-month follow-up. CONCLUSION: This open surgical
      procedure is a safe and effective treatment for endotension and can avoid
      conversion. More experience is needed for definitive evaluation.

PMID- 18729552
TI  - Reduced strain in abdominal aortic aneurysms after endovascular repair.
AB  - PURPOSE: To compare in vivo strain in abdominal aortic aneurysms before and after
      endovascular aneurysm repair (EVAR), thereby obtaining a quantitative measure of
      changes in mechanical burden on the aneurysm wall. METHOD: Transabdominal
      ultrasound was acquired from 10 patients (9 men; median age 76 years, range 61
      83) 1 day before and 2 days after elective EVAR. Strain was estimated as the
      relative cyclic elongation and contraction of the wall tissue in a number of
      connected segments along the aneurysm circumference. For each time instance of
      the cardiac cycle, the maximum and the average strain values along the
      circumference were recorded. The temporal maximums of these parameters (defined
      as the maximum strain and the peak average strain, respectively) were compared
      before and after EVAR. RESULTS: Both maximum strain and peak average strain were
      reduced following EVAR by 41% (range 35%-63%) and 68% (range 41%-93%),
      respectively. Despite the reduction, cyclic strain was still evident after the
      stent-graft was placed, even when no evidence of endoleak was found. Further, the
      strain values were inhomogeneous along the circumference, both before and after
      treatment. In 2 cases, endoleak was proven by routine computed tomography; the
      relative reduction in maximum strain was slightly less in these cases (35% and
      38%) compared to those without endoleak (45%, range 38%-63%). No difference was
      found in reduction of peak average strain. CONCLUSION: Strain is significantly
      reduced after EVAR, but there may still be a certain level of strain after the
      treatment. The strain values are inhomogeneous along the circumference both
      before and after treatment. These results encourage further investigation to
      evaluate the potential for using circumferential strain as an additional
      indicator of outcome after endovascular repair.

PMID- 18729553
TI  - Acute and long-term outcome of endovascular therapy for aortoiliac occlusive
      lesions stratified according to the TASC classification: a single-center
      experience.
AB  - PURPOSE: To compare acute and long-term outcomes of endovascular therapy for TASC
      (TransAtlantic Inter-Society Consensus) A and B lesions versus TASC C and D
      lesions. METHODS: Based on a prospectively maintained database, a retrospective
      analysis was conducted of 375 symptomatic patients (335 men; mean age 63+/-8
      years) who underwent 438 interventions for aortoiliac arterial obstructions.
      Lesions were stratified according to the TASC II classification: 259 (59%)
      procedures involved TASC A/B lesions, while 113 (26%) were for TASC C and 66
      (15%) for TASC D lesions. RESULTS: The baseline characteristics of patients with
      TASC A/B lesions differed significantly in the ankle-brachial index (ABI),
      occurrence of renal insufficiency, and lesion characteristics from those with
      TASC C or D lesions. Acute treatment success, defined as residual stenosis <30%,
      was 100%, 96%, 93%, and 100% for TASC A, B, C, and D lesions, respectively. The
      primary 1-year patency rate, which was 86% for the entire study cohort, was
      similar for all TASC classifications (89%, 86%, 86%, 85% for TASC A to D lesions,
      respectively). In the TASC A/B cohort, the 5-year event-free survival (70%) was
      not significantly better than in the C/D cohort (57%, p=0.124). The clinical
      outcome, as measured by Rutherford stage and ABI, improved significantly in all
      TASC subgroups after successful intervention and was maintained up to 1 year.
      Stenting was an independent predictor for lower restenosis rates (HR 0.517, 95%
      CI 0.317 to 0.842; p=0.008). CONCLUSION: In experienced hands, endovascular
      therapy of aortoiliac lesions can be successfully performed with sustained long
      term outcome independent of the TASC II classification, even in class D lesions.

PMID- 18729554
TI  - Complex carotid stenting using a coronary technique.
AB  - PURPOSE: To report the utility of a coronary technique to facilitate carotid
      stenting in patients with difficult arch anatomies. TECHNIQUE: When confronted
      with challenging arch anatomy that prevents engaging the common carotid artery
      (CCA) with the guiding sheath using standard techniques, an 8-F left Amplatz
      guiding catheter (AL1) is placed at the origin of the innominate artery. A 0.014
      inch coronary guidewire is advanced into the external carotid artery (ECA), and a
      small monorail coronary balloon is inflated in a small branch of the ECA. The
      balloon/guidewire combination facilitates maneuvering a 0.035-inch Amplatz super
      stiff guidewire through the ECA and then advancing the guiding catheter into the
      CCA. CONCLUSION: This anchoring technique can be a helpful method for cannulating
      the CCA in patients with a complex arch when the ECA is patent.

PMID- 18729555
TI  - A review of the in vivo and in vitro biomechanical behavior and performance of
      postoperative abdominal aortic aneurysms and implanted stent-grafts.
AB  - Endovascular repair of abdominal aortic aneurysms has generated widespread
      interest since the procedure was first introduced two decades ago. It is
      frequently performed in patients who suffer from substantial comorbidities that
      may render them unsuitable for traditional open surgical repair. Although this
      minimally invasive technique substantially reduces operative risk, recovery time,
      and anesthesia usage in these patients, the endovascular method has been prone to
      a number of failure mechanisms not encountered with the open surgical method.
      Based on long-term results of second- and third-generation devices that are
      currently becoming available, this study sought to identify the most serious
      failure mechanisms, which may have a starting point in the morphological changes
      in the aneurysm and stent-graft. To investigate the "behavior" of the aneurysm
      after stent-graft repair, i.e., how its length, angulation, and diameter change,
      we utilized state-of-the-art ex vivo methods, which researchers worldwide are now
      using to recreate these failure modes.

PMID- 18729556
TI  - Aortoduodenal fistulas after endovascular stent-graft repair of abdominal aortic
      aneurysms: single-center experience and review of the literature.
AB  - PURPOSE: To report a single-center experience with aortoduodenal fistula (ADF)
      after successful endovascular aneurysm repair (EVAR) of an infrarenal abdominal
      aortic aneurysm (AAA). METHODS: Five patients (all men; mean age 68.4 years,
      range 60-75) developed an ADF between 18 days to 1 year after successful EVAR
      using 3 types of commercially available endografts: 1 bifurcated Anaconda, 1
      unibody Powerlink, and 3 EndoFit stent-grafts in a tubular (n=1) or
      aortomonoiliac configuration (n=2). The internal iliac artery was not occluded in
      any of the cases. RESULTS: Hematemesis and diffuse abdominal pain constituted the
      main symptoms leading to the diagnosis of ADF, which was confirmed on computed
      tomography. Infection was the etiology of the ADF in 3 patients; all underwent
      emergency surgical exploration, but 1 died in hospital; the other 2 have survived
      from 1 to 3 years after an emergency procedure. The other 2 ADFs developed in
      patients with large type I endoleaks; 1 patient died before surgery could be
      performed and the other one 18 hours after laparotomy. All stent-grafts were
      removed; none displayed any defects. CONCLUSION: ADF is a rare but dangerous
      complication of EVAR. The sequela may be primarily attributed to graft infection,
      as seen in this series. However, the exact pathogenesis of the pathology remains
      largely unknown. Prompt diagnosis and intervention are crucial to avoid a fatal
      outcome.

PMID- 18729557
TI  - Transcatheter arterial embolization for segmental arterial mediolysis.
AB  - PURPOSE: To report outcomes of transcatheter arterial embolization for segmental
      arterial mediolysis (SAM), a vascular disorder characterized by angiographically
      documented fusiform aneurysms separated by areas of normal appearing vessel in
      the celiac or mesenteric arteries. CASE REPORTS: Four patients (3 men; median age
      70 years, range 57-77) had a presumptive diagnosis of SAM; the possibility of
      vasculitis was ruled out based on clinical and laboratory findings. Three
      patients were symptomatic, with aneurysm rupture; the fourth patient was
      diagnosed incidentally. Coil embolization was used in 3 cases and N-butyl
      cyanoacrylate in the other. There was no re-rupture. One patient developed a
      focal dissection of the superior mesenteric artery 9 months after middle colic
      artery embolization. Another patient died of perforation of the lower
      gastrointestinal tract 3 months after treatment, but the cause was unknown;
      mesenteric ischemia from embolization and arteriopathy could not be ruled out.
      CONCLUSION: Transcatheter embolization is useful for SAM. However, it is likely
      that the morphology associated with SAM transforms rapidly, so patients
      undergoing mesenteric artery embolization should be monitored at short intervals.

PMID- 18729558
TI  - Homocysteine, the cholesterol of the 21st century. Impact of hyperhomocysteinemia
      on patency and amputation-free survival after intervention for critical limb
      ischemia.
AB  - PURPOSE: To assess the prevalence of hyperhomocysteinemia and determine any
      correlation to the clinical and technical outcome of peripheral arterial
      revascularization for critical limb ischemia (CLI). METHODS: Between October 1,
      2002, and December 31, 2006, 953 revascularization procedures were performed for
      CLI in a high-volume tertiary referral vascular/endovascular unit. Fasting plasma
      homocysteine was accurately measured preoperatively in 225 patients (124 men;
      mean age 75.8 years, range 45-98), who formed the basis for the study. All
      patients had multilevel disease (TASC II C and D lesions), and 73% had single
      vessel runoff. Composite primary endpoints included primary, assisted primary,
      and secondary patency; amputation-free survival; and all-cause mortality.
      RESULTS: The prevalence of hyperhomocysteinemia was 30% [69 patients (36 men;
      mean age 78.2 years, range 53-93)]; most (88%) of the patients showed a mild
      elevation in homocysteine (13-20 micromol/L). Patients with hyperhomocysteinemia
      had significantly lower primary, assisted primary, and secondary patency rates at
      all intervals to 36 months (3.3%, 10.8%, and 11.2%, respectively; p<0.001) after
      the intervention compared to patients with normal homocysteine levels (50.8%,
      54.6%, and 57.1%, respectively). The mean amputation-free survival was
      significantly lower for patients with hyperhomocysteinemia (54.8% versus 81.0%,
      p=0.008). Overall, 27% of the normal homocysteine group progressed to vessel
      occlusion compared to 65% of the hyperhomocysteinemia group (p<0.0001). There was
      no significant difference between groups with respect to 4-year cumulative all
      cause mortality (p=0.331). In a multivariate logistic regression analysis, only a
      homocysteine level >13.0 micromol/L was found to be significantly associated with
      adverse outcomes, such as amputation (OR=3.4, 95% CI 1.27 to 9.01; p=0.015) and
      graft occlusion (OR=7.97, 95% CI 3.63 to 17.5; p<0.0001). CONCLUSION:
      Hyperhomocysteinemia appears to be an independent risk factor for the progression
      of vascular disease and is an adverse prognostic factor for CLI patients
      undergoing peripheral arterial revascularization.

PMID- 18729559
TI  - Midterm results of a modified technique for implanting tube grafts during
      endovascular abdominal aortic aneurysm repair.
AB  - PURPOSE: To retrospectively analyze the efficacy and midterm results of
      endovascular aneurysm repair (EVAR) with a tubular stent-graft using 2 different
      implantation techniques. METHODS: Between November 2004 and September 2007, 53
      patients (49 men; mean age 68.5+/-8.6 years, range 40-80) were treated with the
      EndoFit tube stent-graft. The majority (45, 85%) were treated using the trombone
      technique, in which 2 tubular aortoaortic endografts were deployed with 4 to 8 cm
      of overlap. This subgroup was compared to the 8 patients who received single tube
      grafts. RESULTS: Technical and procedural success were 100%; perioperative
      mortality was 0%. Operative results were similar for patients treated with 1
      graft versus those treated with the overlapping trombone technique. The overall
      device-related complication rate was significantly lower for patients treated
      with the trombone technique (11% versus 75%, p<0.001). Mean follow-up was 24
      months (range 6-36). Endoleak type II occurred in 3 (5.7%) cases. Three (5.7%)
      patients died, 1 from an aortoduodenal fistula secondary to a proximal type I
      endoleak and 2 from acute myocardial infarction. CONCLUSION: The tubular EndoFit
      device appears both safe and effective in terms of midterm clinical outcome,
      especially when the trombone technique is utilized. It compares favorably with
      previously reported EVAR results.

PMID- 18729560
TI  - Prevalence of carotid stent fractures in a single-center experience.
AB  - PURPOSE: To assess the prevalence of carotid stent fractures and quantify any
      associated restenosis or clinical events in a single-center experience. METHODS:
      Seventy-eight consecutive patients were recorded in a prospective database
      between 2003 and 2007. Nearly two thirds (51, 65%) were available for follow-up,
      which included magnified multiplanar radiography and selective duplex
      ultrasonographic studies to evaluate fracture and restenosis in 53 self-expanding
      stents (49 open-cell and 4 closed-cell designs). The images were assessed
      independently by 2 vascular radiologists blinded to the patients' clinical data.
      RESULTS: There was 1 (1.9%) stent fracture with no associated adverse events or
      restenosis. Six (11%) stents had an irregular "fish-scale" appearance that was
      easily confused for fracture and seen only in the open-cell stents. CONCLUSION:
      Stent fractures do occur in the carotid artery; however, they are rare and, in
      our experience, have no clinical sequelae. Radiological assessment should be
      incorporated into clinical and ultrasound surveillance protocols.

PMID- 18729561
TI  - Multislice CT angiography in the follow-up of fenestrated endovascular grafts:
      effect of slice thickness on 2D and 3D visualization of the fenestration stents.
AB  - PURPOSE: To investigate the effect of multislice computed tomography (CT)
      protocols on the visualization of target vessel stents in patients with abdominal
      aortic aneurysm (AAA) treated with fenestrated endovascular grafts. METHODS:
      Twenty-one patients (19 men; mean age 75 years, range 63-86) undergoing
      fenestrated endovascular repair of AAA were retrospectively studied. Multislice
      CT angiography was performed with several protocols, and the section thicknesses
      used in each were compared to identify any relationship between slice thickness
      and target vessel stents visualized on 2-dimensional (2D) axial, multiplanar
      reformatted (MPR), and 3-dimensional (3D) virtual intravascular endoscopy (VIE)
      images. Image quality was assessed based on the degree of artifacts and their
      effect on the ability to visualize the configuration, intra-aortic location, and
      intraluminal appearance of the target vessel stents and measure their protrusion
      into the aortic lumen. RESULTS: There were 7 different multislice CT scanning
      protocols employed in the 21 patients (25 datasets, with 2 sets of follow-up
      images in 4 patients). The slice thicknesses and numbers (n) of studies included
      were 0.5 (n=3), 0.625 (n=6), 1.0 (n=1), 1.25 (n=9), 2.5 (n=3), 3.0 (n=1), and 5.0
      mm (n=2). Of these CT protocols, images (especially 2D/3D reconstructions)
      acquired at 2.5, 3.0, and 5.0 mm were significantly compromised by interference
      from artifacts. Images acquired with a slice thickness of 1.0 or 1.25 mm were
      scored equal to or lower than those acquired with a submillimeter section
      thickness (0.5 or 0.625 mm), with minor degrees of artifacts resulting in
      acceptable image quality. CONCLUSION: Visualization of the target vessel stents
      depends on the appropriate selection of multislice CT scanning protocols. Our
      results showed that studies performed with a slice thickness of 1.0 or 1.25 mm
      produced similar image quality to those with a thickness of 0.5 or 0.625 mm.
      Submillimeter slices are not recommended in imaging patients treated with
      fenestrated stent-grafts, as they did not add additional information to the
      visualization.

PMID- 18729562
TI  - In vivo imaging of abdominal aortic aneurysms: increased FDG uptake suggests
      inflammation in the aneurysm wall.
AB  - PURPOSE: To study the potential of integrated positron emission tomography and
      computed tomography (PET/CT) to identify aneurysm wall inflammation. METHODS: The
      level of F18-fluorodeoxyglucose (FDG) uptake was studied in aneurysmal and normal
      sized aortas of 34 male patients [17 with abdominal aortic aneurysm (AAA) and 17
      age-matched controls] identified in a database of 278 consecutive patients
      evaluated for staging of primary lung cancer. The maximal standardized uptake
      value (SUV) was calculated to quantify FDG uptake in the AAA wall. RESULTS: AAAs
      showed significantly higher FDG uptake than the normal-sized aorta in age-matched
      controls (SUV 2.52+/-0.52 versus 1.78+/-0.45, respectively; p<0.001). The level
      of FDG uptake did not correlate with maximal aneurysm diameter (r=0.09; 95% CI 
      0.42 to 0.56; p=0.7). CONCLUSION: FDG-PET/CT is a promising technique to identify
      inflammation of the aneurysm wall. Irrespective of aneurysm diameter,
      asymptomatic AAAs show more FDG uptake and more inflammatory activity in the wall
      than the non-dilated abdominal aorta of sex/age-matched controls. Future studies
      will be directed at the predictive value of increased FDG uptake for aneurysm
      wall strength, rupture risk, and the utility of FDG-PET/CT in assessing the
      effect of medical interventions.

PMID- 18729563
TI  - Complications after peripheral vascular interventions in octogenarians.
AB  - PURPOSE: To investigate the incidence of complications after peripheral vascular
      interventions in patients aged 80 years and older compared to patients below the
      age of 80. METHODS: During a 20-month period, 619 consecutive patients (354 men;
      mean age 67 years, range 59-87) undergoing balloon angioplasty and stenting for
      lower limb revascularization were enrolled in the study. The incidence of
      procedure-related, access-site, and major complications within 30 days post
      intervention were recorded and compared between patients aged 80 years and older
      (n=72, 11.6%) and those under 80 years of age. RESULTS: Complication rates were
      significantly higher in octogenarians compared to patients below 80 years,
      including the rates of overall complications (18.1% versus 8.5%, p=0.010), major
      complications (11.1% versus 1.8%, p<0.001), all access site complications (12.5%
      versus 4.9%, p=0.009), and access site bleeding complications (12.5% versus 2.2%,
      p<0.001). By multivariable analysis, octogenarians had a 2.49-fold increased
      adjusted risk (95% CI 1.10 to 5.65, p=0.029) for any postintervention
      complication and a 10.99-fold increased adjusted risk (95% CI 2.76 to 45.74,
      p=0.001) for major complications compared to patients below 80 years. No specific
      risk factor for complications or major complications within the octogenarian
      population could be identified. CONCLUSION: Patients aged 80 years and older have
      a dramatically increased risk, particularly for major complications, after
      peripheral vascular interventions. Identification of risk factors and development
      of preventive strategies are urgently needed to improve procedure safety in this
      extremely vulnerable population.

PMID- 18729564
TI  - Nitinol stent implantation in TASC A and B superficial femoral artery lesions:
      the Femoral Artery Conformexx Trial (FACT).
AB  - PURPOSE: To investigate the impact of nitinol stenting of superficial femoral
      artery (SFA) lesions with a maximum length of 10 cm (TASC-II A or B) on 1-year
      outcomes compared to a historical study cohort from the Femoral Artery Stent
      Trial (FAST). METHODS: Between January 2004 and August 2005, 6 study sites
      enrolled 110 symptomatic patients (75 men; mean age 68+/-9 years) with a single
      de novo >70% SFA lesion <10 cm long treated with the self-expanding nitinol
      Conformexx stent. The primary study endpoint was binary restenosis determined by
      duplex ultrasound at 12 months. Secondary 12-month endpoints were target lesion
      revascularization (TLR), ankle-brachial index (ABI), mean Rutherford category, >1
      class change in Rutherford category, and major adverse events. Data were analyzed
      according to the intention-to-treat principle and according to the actual
      treatment received ("on treatment" analysis). Outcomes were compared to the
      historical balloon angioplasty (BA) arm and the Luminexx 3 stent arm of the
      randomized FAST study. RESULTS: Technical success was achieved in 106 (96%)
      patients; at 1 year, the primary endpoint of ultrasound-assessed binary
      restenosis was reached in 14 (23.3%) of 60 patients (95% CI 13.4% to 36%). This
      restenosis rate was lower versus the historical BA (38.6%, p=0.057) or Luminexx 3
      stent controls (31.7%, p=0.284) from FAST. The clinically driven TLR was 7.4% (7
      of 94 clinically controlled patients), which was also lower compared to 18.3%
      (p=0.098) and 14.9% (p=0.267) for the historical BA and Luminexx 3 stent groups,
      respectively. The mean Rutherford category was reduced from 2.75+/-0.79 to 0.94+/
      1.38 (p<0.0001); 85.1% were improved by at least 1 Rutherford category. The ABI
      increased from 0.62+/-0.15 to 0.85+/-0.20 (p<0.0001). CONCLUSION: This study of
      patients with SFA lesions documented favorable outcomes using nitinol stents in
      TASC-II A or B lesions after 1 year. The study was underpowered to prove
      superiority of the Conformexx nitinol stent design compared to historical balloon
      only or Luminexx 3 stent groups.

PMID- 18729565
TI  - Cognitive processes in dissociation: an analysis of core theoretical assumptions.
AB  - Dissociation is typically defined as the lack of normal integration of thoughts,
      feelings, and experiences into consciousness and memory. The present article
      critically evaluates the research literature on cognitive processes in
      dissociation. The authors' review indicates that dissociation is characterized by
      subtle deficits in neuropsychological performance (e.g., heightened
      distractibility). Some of the cognitive phenomena (e.g., weakened cognitive
      inhibition) associated with dissociation appear to be dependent on the emotional
      or attentional context. Contrary to a widespread assumption in the clinical
      literature, dissociation does not appear to be related to avoidant information
      processing. Rather, it is associated with an enhanced propensity toward pseudo
      memories, possibly mediated by heightened levels of interrogative suggestibility,
      fantasy proneness, and cognitive failures. Evidence for a link between
      dissociation and either memory fragmentation or early trauma based on objective
      measures is conspicuously lacking. The authors identify a variety of
      methodological issues and discrepancies that make it difficult to articulate a
      comprehensive framework for cognitive mechanisms in dissociation. The authors
      conclude with a discussion of research domains (e.g., sleep-related experiences,
      drug-related dissociation) that promise to advance our understanding of cognition
      and dissociation.

PMID- 18729566
TI  - The effectiveness of psychotherapeutic interventions for bereaved persons: a
      comprehensive quantitative review.
AB  - Previous quantitative reviews of research on psychotherapeutic interventions for
      bereaved persons have yielded divergent findings and have not included many of
      the available controlled outcome studies. This meta-analysis summarizes results
      from 61 controlled studies to offer a more comprehensive integration of this
      literature. This review examined (a) the absolute effectiveness of bereavement
      interventions immediately following intervention and at follow-up assessments,
      (b) several of the clinically and theoretically relevant moderators of outcome,
      and (c) change over time among recipients of the interventions and individuals in
      no-intervention control groups. Overall, analyses showed that interventions had a
      small effect at posttreatment but no statistically significant benefit at follow
      up. However, interventions that exclusively targeted grievers displaying marked
      difficulties adapting to loss had outcomes that compare favorably with
      psychotherapies for other difficulties. Other evidence suggested that the
      discouraging results for studies failing to screen for indications of distress
      could be attributed to a tendency among controls to improve naturally over time.
      The findings of the review underscore the importance of attending to the targeted
      population in the practice and study of psychotherapeutic interventions for
      bereaved persons.

PMID- 18729567
TI  - Visual search for faces with emotional expressions.
AB  - The goal of this review is to critically examine contradictory findings in the
      study of visual search for emotionally expressive faces. Several key issues are
      addressed: Can emotional faces be processed preattentively and guide attention?
      What properties of these faces influence search efficiency? Is search moderated
      by the emotional state of the observer? The authors argue that the evidence is
      consistent with claims that (a) preattentive search processes are sensitive to
      and influenced by facial expressions of emotion, (b) attention guidance is
      influenced by a dynamic interplay of emotional and perceptual factors, and (c)
      visual search for emotional faces is influenced by the emotional state of the
      observer to some extent. The authors also argue that the way in which contextual
      factors interact to determine search performance needs to be explored further to
      draw sound conclusions about the precise influence of emotional expressions on
      search efficiency. Methodological considerations (e.g., set size, distractor
      background, task set) and ecological limitations of the visual search task are
      discussed. Finally, specific recommendations are made for future research
      directions.

PMID- 18729568
TI  - Sex differences in left-handedness: a meta-analysis of 144 studies.
AB  - Human handedness, a marker for language lateralization in the brain, continues to
      attract great research interest. A widely reported but not universal finding is a
      greater male tendency toward left-handedness. Here the authors present a meta
      analysis of k = 144 studies, totaling N = 1,787,629 participants, the results of
      which demonstrate that the sex difference is both significant and robust. The
      overall best estimate for the male to female odds ratio was 1.23 (95% confidence
      interval = 1.19, 1.27). The widespread observation of this sex difference is
      consistent with it being related to innate characteristics of sexual
      differentiation, and its observed magnitude places an important constraint on
      current theories of handedness. In addition, the size of the sex difference was
      significantly moderated by the way in which handedness was assessed (by writing
      hand or by other means), the location of testing, and the year of publication of
      the study, implicating additional influences on its development.

PMID- 18729571
TI  - Binocular coordination during reading and non-reading tasks.
AB  - The goal of this review is to evaluate the literature on binocular coordination
      during reading and non-reading tasks in adult, child, and dyslexic populations.
      The review begins with a description of the basic characteristics of eye
      movements during reading. Then, reading and non-reading studies investigating
      binocular coordination are evaluated. Areas of future research in the field are
      identified and discussed. Finally, some general conclusions are made regarding
      binocular coordination. The review demonstrates that findings from traditionally
      independent areas of research are largely consistent and complementary.
      Throughout the review, theoretical and methodological commonalities are
      identified and clarified in order to advance current understanding of this
      fundamental aspect of human visual processing.

PMID- 18729569
TI  - Cancer-related fatigue: a systematic and meta-analytic review of non
      pharmacological therapies for cancer patients.
AB  - Cancer-related fatigue (CRF) is a significant clinical problem for more than 10
      million adults diagnosed with cancer each year worldwide. No "gold standard"
      treatment presently exists for CRF. To provide a guide for future research to
      improve the treatment of CRF, the authors conducted the most comprehensive
      combined systematic and meta-analytic review of the literature to date on non
      pharmacological (psychosocial and exercise) interventions to ameliorate CRF and
      associated symptoms (vigor/vitality) in adults with cancer, based on 119
      randomized controlled trials (RCTs) and non-RCT studies. Meta-analyses conducted
      on 57 RCTs indicated that exercise and psychological interventions provided
      reductions in CRF, with no significant differences between these 2 major types of
      interventions considered as a whole. Specifically, multimodal exercise and
      walking programs, restorative approaches, supportive-expressive, and cognitive
      behavioral psychosocial interventions show promising potential for ameliorating
      CRF. The results also suggest that vigor and vitality are distinct phenomena from
      CRF with regard to responsiveness to intervention. With improved methodological
      approaches, further research in this area may soon provide clinicians with
      effective strategies for reducing CRF and enhancing the lives of millions of
      cancer patients and survivors.

PMID- 18729572
TI  - Processes underlying developmental reversals in false-memory formation: comment
      on Brainerd, Reyna, and Ceci (2008).
AB  - C. J. Brainerd, V. F. Reyna, and S. J. Ceci (2008) reviewed compelling evidence
      of developmental reversals in false-memory formation (i.e., younger children
      exhibit lower false-memory rates than do older children and adults) and proposed
      that this phenomenon depends on the development of gist processing (i.e., the
      ability to identify and process the semantic theme of word lists, events, etc.).
      A full understanding of development reversals, however, cannot be achieved
      without further characterizing the role played by complementary or opposing
      processes. Suggestions for future research are made from this perspective.

PMID- 18729573
TI  - What is false memory development the development of? Comment on Brainerd, Reyna,
      and Ceci (2008).
AB  - In this commentary, assumptions about the nature and development of children's
      false memories as described in a recent article by C. J. Brainerd, V. F. Reyna,
      and S. J. Ceci (2008) are reviewed. Specifically, questions are raised about what
      drives the development of false memories in fuzzy-trace theory (FTT). Recent
      studies that challenge a core assumption of FTT, that false memory illusions
      increase across development as children learn to establish meaningful connections
      across items (i.e., establish gist), are discussed. An alternative
      conceptualization of the development of false memory illusions, associative
      activation theory (AAT), is presented. AAT provides as viable an account of the
      development of false memory illusions as does FTT and anticipates a unique set of
      outcomes that have recently appeared in the developmental literature on false
      memory illusions.

PMID- 18729575
TI  - Automatic vigilance for negative words in lexical decision and naming: comment on
      Larsen, Mercer, and Balota (2006).
AB  - An automatic vigilance hypothesis states that humans preferentially attend to
      negative stimuli, and this attention to negative valence disrupts the processing
      of other stimulus properties. Thus, negative words typically elicit slower color
      naming, word naming, and lexical decisions than neutral or positive words.
      Larsen, Mercer, and Balota analyzed the stimuli from 32 published studies, and
      they found that word valence was confounded with several lexical factors known to
      affect word recognition. Indeed, with these lexical factors covaried out, Larsen
      et al. found no evidence of automatic vigilance. The authors report a more
      sensitive analysis of 1011 words. Results revealed a small but reliable valence
      effect, such that negative words (e.g., "shark") elicit slower lexical decisions
      and naming than positive words (e.g., "beach"). Moreover, the relation between
      valence and recognition was categorical rather than linear; the extremity of a
      word's valence did not affect its recognition. This valence effect was not
      attributable to word length, frequency, orthographic neighborhood size,
      contextual diversity, first phoneme, or arousal. Thus, the present analysis
      provides the most powerful demonstration of automatic vigilance to date.

PMID- 18729578
TI  - Resting respiratory sinus arrhythmia buffers against rejection sensitivity via
      emotion control.
AB  - Emerging evidence suggests that high resting heart rate variability in the
      respiratory frequency band, or respiratory sinus arrhythmia (RSA) may capture
      individual differences in the capacity to engage in situationally appropriate
      regulation of affect and behavior. The authors therefore hypothesized that high
      RSA may act as a protective factor against difficulties controlling negative
      affect and hostile behaviors in conflicts with romantic partners in highly
      rejection-sensitive individuals--a population otherwise vulnerable to these
      responses. Results were consistent with this hypothesis such that highly
      rejection-sensitive participants reported less emotion control and more hostility
      in conflicts only if they were also low in RSA. Furthermore, emotion control
      mediated the joint effect of rejection-sensitivity and RSA on hostile conflict
      behavior. These results are consistent with the argument that resting RSA is a
      marker of flexible responding in the context of highly emotional situations, and
      further suggest that it may serve as a protective factor particularly in
      vulnerable populations.

PMID- 18729579
TI  - Individual differences in negative affect repair.
AB  - The extant literature implicates affect repair ability as one source of
      individual differences in negative affect. Emerging from this literature are
      three regulatory traits that should predict repair ability (negative mood
      regulation expectancies, monitoring, labeling), yet no experimental examination
      of this possibility exists. Two studies explored this issue. Participants
      (Ns=305, 146) watched negative affect-inducing videos and completed a repair or
      control writing task, before and after which they reported their affect. Results
      revealed wide individual differences in repair ability. Specifically,
      participants with high expectancies of repair success and those who attend to and
      understand their affect experienced the largest decreases in negative affect and
      largest increases in positive affect following the repair tasks. These findings
      advance understanding of individual differences in affect regulation and have
      implications for future research.

PMID- 18729581
TI  - Emotions evoked by the sound of music: characterization, classification, and
      measurement.
AB  - One reason for the universal appeal of music lies in the emotional rewards that
      music offers to its listeners. But what makes these rewards so special? The
      authors addressed this question by progressively characterizing music-induced
      emotions in 4 interrelated studies. Studies 1 and 2 (n=354) were conducted to
      compile a list of music-relevant emotion terms and to study the frequency of both
      felt and perceived emotions across 5 groups of listeners with distinct music
      preferences. Emotional responses varied greatly according to musical genre and
      type of response (felt vs. perceived). Study 3 (n=801)--a field study carried out
      during a music festival--examined the structure of music-induced emotions via
      confirmatory factor analysis of emotion ratings, resulting in a 9-factorial model
      of music-induced emotions. Study 4 (n=238) replicated this model and found that
      it accounted for music-elicited emotions better than the basic emotion and
      dimensional emotion models. A domain-specific device to measure musically induced
      emotions is introduced--the Geneva Emotional Music Scale.

PMID- 18729580
TI  - Individual differences in learning the affective value of others under minimal
      conditions.
AB  - This paper provides the first demonstration that people can learn about the
      positive and negative value of other people (e.g., neutral faces) under minimal
      learning conditions, with stable individual differences in this learning. In four
      studies, participants viewed neutral faces paired with sentences describing
      positive, negative or neutral behaviors on either two (Study 1) or four (Studies
      2, 3, and 4) occasions. Participants were later asked to judge the valence of the
      faces alone. Studies 1 and 2 demonstrated that learning does occur under minimal
      conditions. Study 3 and 4 further demonstrated that the degree of learning was
      moderated by Extraversion. Finally, Study 4 demonstrated that initial learning
      persisted over a period of 2 days. Implications for affective processing and
      person perception are discussed.

PMID- 18729582
TI  - Masked fearful faces modulate the orienting of covert spatial attention.
AB  - Dot probe studies indicate that masked fearful faces modulate spatial attention.
      However, without a baseline to compare congruent and incongruent reaction times,
      it is unclear which aspect(s) of attention (orienting or disengagement) is
      affected. Additionally, backward masking studies commonly use a neutral face as
      the mask stimulus. This method results in greater perceptual inconsistencies for
      fearful as opposed to neutral faces. Therefore, it is currently unclear whether
      the effects of backward masked fearful faces are due to the fearful nature of the
      face or perceptual inconsistencies. Equally unclear, is whether this spatial
      attention effect is due to orienting or disengagement. Two modified dot probe
      experiments with neutral (closed mouth in Experiment 1) and smiling (open mouth
      in Experiment 2) masks were used to determine the role of perceptual
      inconsistencies in mediating the spatial attention effects elicited by masked
      fearful faces. The results indicate that masked fearful faces modulate the
      orienting of spatial attention, and it appears that this effect is due to the
      fearful nature of the face rather than perceptual inconsistencies between the
      initial faces and masks.

PMID- 18729583
TI  - False recognition of facial expressions of emotion: causes and implications.
AB  - This article examines the importance of semantic processes in the recognition of
      emotional expressions, through a series of three studies on false recognition.
      The first study found a high frequency of false recognition of prototypical
      expressions of emotion when participants viewed slides and video clips of
      nonprototypical fearful and happy expressions. The second study tested whether
      semantic processes caused false recognition. The authors found that participants
      made significantly higher error rates when asked to detect expressions that
      corresponded to semantic labels than when asked to detect visual stimuli.
      Finally, given that previous research reported that false memories are less
      prevalent in younger children, the third study tested whether false recognition
      of prototypical expressions increased with age. The authors found that 67% of
      eight- to nine-year-old children reported nonpresent prototypical expressions of
      fear in a fearful context, but only 40% of 6- to 7-year-old children did so.
      Taken together, these three studies demonstrate the importance of semantic
      processes in the detection and categorization of prototypical emotional
      expressions.

PMID- 18729584
TI  - New paradigms for assessing emotional intelligence: theory and data.
AB  - This article describes the development and validation of 2 measures of emotional
      intelligence (EI): the Situational Test of Emotional Understanding (STEU) and the
      Situational Test of Emotion Management (STEM). Study 1 (N=207 psychology
      students) examines multiple sources of validity evidence: relationships with EI,
      vocabulary, personality, and emotion-related criteria. Study 2 (N=149 white
      collar volunteers) relates STEU and STEM scores to clinical symptoms, finding
      relationships to anxiety and stress for both tests, and to depression for the
      STEM. It is concluded that new performance-based approaches to test development,
      such as the present ones, might be useful in distinguishing between test and
      construct effects. Implications for expanding theory and for developing EI
      interventions are discussed.

PMID- 18729585
TI  - Affective ratings and startle modulation in people with nonclinical depression.
AB  - This study tested predictions based on the emotion context insensitivity (ECI)
      hypothesis of Rottenberg, Gross, and Gotlib (2005) that a nonclinical sample of
      people with depressive symptoms would show reduced responses to both positive and
      negative stimuli relative to people without depression and would show an enhanced
      response to novelty. Seventy individuals completed diagnostic questionnaires,
      made ratings of 21 affectively valenced pictures, and then viewed the same 21
      pictures and 21 novel pictures while startle blink responses were recorded from
      electromyographic activity of the orbicularis oculi. People with scores on the
      Beck Depression Inventory (BDI; Beck, Ward, Mendelson, Mock, & Erbaugh, 1961)
      indicative of depression demonstrated a lack of affective startle modulation
      compared to the nondepression group. For all participants, the startle response
      was larger for novel pictures than for previously viewed pictures, but scores on
      the BDI were not related to response to novelty. Taken together, the results
      suggest that nonclinical depression is associated with a lack of affective
      modulation of startle, as has been shown for clinical depression.

PMID- 18729586
TI  - Investigating models of affect: relationships among EEG alpha asymmetry,
      depression, and anxiety.
AB  - The approach-withdrawal and valence-arousal models both predict that depressive
      and anxious profiles will be associated with relatively reduced left frontal and
      increased right frontal activity respectively, while the valence-arousal model
      also proposes a dissociation by lower and higher right parietotemporal activity,
      respectively. Recent work further suggests that subtypes of anxiety disorders may
      be characterized by distinctive patterns of activity depending on their type of
      arousal (anxious arousal/apprehension). The aim of this study was to investigate
      the relationships among nonclinical depression/anxiety and lateralized
      frontal/parietotemporal activity by categorizing participants (N=428) on the
      basis of both negative mood and alpha EEG. Key findings include: (i) greater
      right frontal lateralization in anxious participants, symmetrical frontal
      activity in depressed/comorbid, and left frontal lateralization in healthy
      controls; (ii) right frontal lateralization in anxious arousal participants, left
      frontal and right parietotemporal lateralization in anxious apprehension; (iii)
      bilateral increase in frontal and increased right parietotemporal activity in
      depressed/comorbid participants. Findings support predictions for frontal but not
      posterior regions. Grouping on the basis of EEG may not be reciprocally
      predictive of negative mood groupings, suggesting involvement of additional
      factors.

PMID- 18729587
TI  - Emotional expression modulates perceived gaze direction.
AB  - Gaze perception is an important social skill, as it portrays information about
      what another person is attending to. Gaze direction has been shown to affect
      interpretation of emotional expression. Here the authors investigate whether the
      emotional facial expression has a reciprocal influence on interpretation of gaze
      direction. In a forced-choice yes-no task, participants were asked to judge
      whether three faces expressing different emotions (anger, fear, happiness, and
      neutral) in different viewing angles were looking at them or not. Happy faces
      were more likely to be judged as looking at the observer than were angry,
      fearful, or neutral faces. Angry faces were more often judged as looking at the
      observer than were fearful and neutral expressions. These findings are discussed
      on the background of approach and avoidance orientation of emotions and of the
      self-referential positivity bias.

PMID- 18729588
TI  - Guarding against hostile thoughts: trait anger and the recruitment of cognitive
      control.
AB  - Trait anger is a robust predictor of the angry and aggressive response to hostile
      situational input, but it is important to better understand the mechanisms
      underlying this dimension of personality. The present two studies (total N=106)
      examined the possibility that individuals low in trait anger systematically
      recruit cognitive control resources within hostile contexts. These resources
      would likely be useful in facilitating emotion regulation operations. In support
      of this cognitive control framework, Experiment 1 found that low (but not high)
      trait anger individuals exhibited superior response-switching abilities in a
      hostile stimulus context. Experiment 2 conceptually replicated this pattern using
      a different cognitive control measure related to flanker interference effects.
      The convergence of findings across studies provides one likely mechanism for the
      reduced levels of reactivity at low levels of trait anger. Findings are discussed
      in relation to broader theories of trait anger and emotion regulation.

PMID- 18729589
TI  - Variation in the serotonin transporter gene modulates selective attention to
      threat.
AB  - The 5-HTTLPR is an insertion/deletion polymorphism in the promoter region of the
      serotonin transporter gene. Prior research has revealed associations between the
      short-allele variant of this polymorphism, enhanced self-reported negative
      emotionality, and hypersensitivity of fear relevant neural circuits. In a sample
      of 50 healthy women we examined the role of 5-HTTLPR for cognitive-affective
      processing of phylogenetical fear-relevant stimuli (spiders) in a dot probe task.
      In contrast to homozygote long-allele carriers (ll), participants carrying at
      least 1 short allele (ss and sl) selectively shifted attention toward pictures of
      spiders, when these were presented for a duration of 2,000 ms. These results
      argue for an involvement of 5-HTTLPR in cognitive processing of threatening
      stimuli and thus, underpin its general role for individual differences in
      negative affect.

PMID- 18729591
TI  - Forgetting in immediate serial recall: decay, temporal distinctiveness, or
      interference?
AB  - Three hypotheses of forgetting from immediate memory were tested: time-based
      decay, decreasing temporal distinctiveness, and interference. The hypotheses were
      represented by 3 models of serial recall: the primacy model, the SIMPLE (scale
      independent memory, perception, and learning) model, and the SOB (serial order in
      a box) model, respectively. The models were fit to 2 experiments investigating
      the effect of filled delays between items at encoding or at recall. Short delays
      between items, filled with articulatory suppression, led to massive impairment of
      memory relative to a no-delay baseline. Extending the delays had little
      additional effect, suggesting that the passage of time alone does not cause
      forgetting. Adding a choice reaction task in the delay periods to block attention
      based rehearsal did not change these results. The interference-based SOB fit the
      data best; the primacy model overpredicted the effect of lengthening delays, and
      SIMPLE was unable to explain the effect of delays at encoding. The authors
      conclude that purely temporal views of forgetting are inadequate.

PMID- 18729590
TI  - What is the shape of developmental change?
AB  - Developmental trajectories provide the empirical foundation for theories about
      change processes during development. However, the ability to distinguish among
      alternative trajectories depends on how frequently observations are sampled. This
      study used real behavioral data, with real patterns of variability, to examine
      the effects of sampling at different intervals on characterization of the
      underlying trajectory. Data were derived from a set of 32 infant motor skills
      indexed daily during the first 18 months. Larger sampling intervals (2-31 days)
      were simulated by systematically removing observations from the daily data and
      interpolating over the gaps. Infrequent sampling caused decreasing sensitivity to
      fluctuations in the daily data: Variable trajectories erroneously appeared as
      step functions, and estimates of onset ages were increasingly off target.
      Sensitivity to variation decreased as an inverse power function of sampling
      interval, resulting in severe degradation of the trajectory with intervals longer
      than 7 days. These findings suggest that sampling rates typically used by
      developmental researchers may be inadequate to accurately depict patterns of
      variability and the shape of developmental change. Inadequate sampling regimes
      therefore may seriously compromise theories of development.

PMID- 18729594
TI  - An integrated model of cognitive control in task switching.
AB  - A model of cognitive control in task switching is developed in which controlled
      performance depends on the system maintaining access to a code in episodic memory
      representing the most recently cued task. The main constraint on access to the
      current task code is proactive interference from old task codes. This
      interference and the mechanisms that contend with it reproduce a wide range of
      behavioral phenomena when simulated, including well-known task-switching effects,
      such as latency and error switch costs, and effects on which other theories are
      silent, such as with-run slowing and within-run error increase. The model
      generalizes across multiple task-switching procedures, suggesting that episodic
      task codes play an important role in keeping the cognitive system focused under a
      variety of performance constraints.

PMID- 18729592
TI  - The overlap model: a model of letter position coding.
AB  - Recent research has shown that letter identity and letter position are not
      integral perceptual dimensions (e.g., jugde primes judge in word-recognition
      experiments). Most comprehensive computational models of visual word recognition
      (e.g., the interactive activation model, J. L. McClelland & D. E. Rumelhart,
      1981, and its successors) assume that the position of each letter within a word
      is perfectly encoded. Thus, these models are unable to explain the presence of
      effects of letter transposition (trial-trail), letter migration (beard-bread),
      repeated letters (moose-mouse), or subset/superset effects (faulty-faculty). The
      authors extend R. Ratcliff's (1981) theory of order relations for encoding of
      letter positions and show that the model can successfully deal with these
      effects. The basic assumption is that letters in the visual stimulus have
      distributions over positions so that the representation of one letter will extend
      into adjacent letter positions. To test the model, the authors conducted a series
      of forced-choice perceptual identification experiments. The overlap model
      produced very good fits to the empirical data, and even a simplified 2-parameter
      model was capable of producing fits for 104 observed data points with a
      correlation coefficient of .91.

PMID- 18729595
TI  - Attentional, associative, and configural mechanisms in extinction.
AB  - The participation of attentional and associative mechanisms in extinction,
      spontaneous recovery, external disinhibition, renewal, reinstatement, and
      reacquisition was evaluated through computer simulations with an extant
      computational model of classical conditioning (N. A. Schmajuk, Y. Lam, & J. A.
      Gray, 1996; N. A. Schmajuk & J. A. Larrauri, 2006). The model assumes that
      attention to stimuli (controlled by environmental novelty) and associations
      between stimuli interact during memory storage (learning) and retrieval
      (performance). Computer simulations indicated that a combination of attentional
      and associative mechanisms might be sufficient to describe most of the properties
      of extinction. However, configural mechanisms seem necessary to describe the
      properties of cues that precede the target stimulus during extinction (extinction
      cues) and might improve the description of some experimental results regarding
      the associative properties of the extinction context. These configural mechanisms
      can be easily integrated into the present version of the model.

PMID- 18729596
TI  - Laminar cortical dynamics of cognitive and motor working memory, sequence
      learning and performance: toward a unified theory of how the cerebral cortex
      works.
AB  - How does the brain carry out working memory storage, categorization, and
      voluntary performance of event sequences? The LIST PARSE neural model proposes an
      answer that unifies the explanation of cognitive, neurophysiological, and
      anatomical data. It quantitatively simulates human cognitive data about immediate
      serial recall and free recall, and monkey neurophysiological data from the
      prefrontal cortex obtained during sequential sensory-motor imitation and planned
      performance. The model clarifies why spatial and non-spatial working memories
      share the same type of circuit design. It proposes how laminar circuits of
      lateral prefrontal cortex carry out working memory storage of event sequences
      within layers 6 and 4, how these event sequences are unitized through learning
      into list chunks within layer 2/3, and how these stored sequences can be recalled
      at variable rates that are under volitional control by the basal ganglia. These
      laminar prefrontal circuits are variations of visual cortical circuits that
      explained data about how the brain sees. These examples from visual and
      prefrontal cortex illustrate how laminar neocortex can represent both spatial and
      temporal information, and open the way towards understanding how other behaviors
      derive from shared laminar neocortical designs.

PMID- 18729597
TI  - A general connectionist model of attitude structure and change: the ACS
      (Attitudes as Constraint Satisfaction) model.
AB  - A localist, parallel constraint satisfaction, artificial neural network model is
      presented that accounts for a broad collection of attitude and attitude-change
      phenomena. The network represents the attitude object and cognitions and beliefs
      related to the attitude, as well as how to integrate a persuasive message into
      this network. Short-term effects are modeled by activation patterns due to
      parallel constraint satisfaction processes, and long-term effects are modeled by
      weight changes due to the settling patterns of activation. Phenomena modeled
      include thought-induced attitude polarization, elaboration and attitude strength,
      motivated reasoning and social influence, an integrated view of heuristic versus
      systematic persuasion, and implicit versus explicit attitude change. Results of
      the simulations are consistent with empirical results. The same set of simple
      mechanisms is used to model all the phenomena, which allows the model to offer a
      parsimonious theoretical account of how structure can impact attitude change.
      This model is compared with previous computational approaches to attitudes, and
      implications for attitude research are discussed.

PMID- 18729598
TI  - Mental models and the suppositional account of conditionals.
AB  - The mental model theory of conditional reasoning presented by P. N. Johnson-Laird
      and R. M. J. Byrne (2002) has recently been the subject of criticisms (e.g., J.
      St. B. T. Evans, D. E. Over, & S. J. Handley, 2005). The authors argue that the
      theoretical conflict can be resolved by differentiating 2 kinds of reasoning,
      reasoning about possibilities given the truth of assertions and reasoning about
      the truth of assertions given possibilities. The standard mental model theory
      accounts for the former kind of reasoning but does not adequately account for the
      latter, contrary to the suppositional approach favored by J. St. B. T. Evans et
      al. (2005). The authors thus propose a modified mental model theory of
      conditionals that reconciles the 2 theoretical approaches. It is demonstrated
      that this theory is able to explain the key findings that have been opposed to
      the standard theory by J. St. B. T. Evans et al. and makes new predictions that
      are empirically verified.

PMID- 18729600
TI  - What must a psychological theory of reasoning explain? Comment on Barrouillet,
      Gauffroy, and Lecas (2008).
AB  - In this comment, it is argued that the modification of mental models theory of
      conditional inference proposed by P. Barrouillet, C. Gauffroy, and J.-F. Lecas to
      deal with truth value gaps merely patches up a problem in the theory, rather than
      accomplishing the fundamental and systematic revision that is necessary. It is
      argued that P. Barrouillet et al.'s modified mental model theory fails to meet
      the criteria of good theory of reasoning by invoking an algorithmic-level
      distinction to resolve a failing in the computational-level theory of the task.

PMID- 18729602
TI  - Issues with the SIMPLE model: comment on Brown, Neath, and Chater (2007).
AB  - SIMPLE (G. D. A. Brown, I. Neath, & N. Chater, 2007) attempts to explain data
      from serial recall and free recall in the same theoretical framework. While it
      can fit the free-recall serial-position curves that are the cornerstone of the 2
      store buffer model, it does not address 2 classic issues in short-term memory
      research: similarity effects and presentation-rate effects. Similarity effects in
      free recall led to important work on organization in free recall, whereas
      similarity effects in serial recall led to the phonological basis of short-term
      memory. Presentation-rate effects operate quite differently in free and serial
      recall. The model also does not consider recall order effects or interresponse
      times in free recall, which may be problematic.

PMID- 18729604
TI  - Motivational pathways to alcohol use and abuse among Black and White adolescents.
AB  - Using data from a biracial community sample of adolescents, the present study
      examined trajectories of alcohol use and abuse over a 15-year period, from
      adolescence into young adulthood, as well as the extent to which these
      trajectories were differentially predicted by coping and enhancement motives for
      alcohol use among the 2 groups. Coping and enhancement motivations (M. L. Cooper,
      1994) refer to the strategic use of alcohol to regulate negative and positive
      emotions, respectively. Results showed that Black and White youth follow distinct
      alcohol trajectories from adolescence into young adulthood and that these
      trajectories are differentially rooted in the regulation of negative and positive
      emotions. Among Black drinkers, coping motives assessed in adolescence more
      strongly forecast differences in alcohol involvement into their early 30s,
      whereas enhancement motives more strongly forecast differences among White
      drinkers. Results of the present study suggest that different models may be
      needed to account for drinking behavior among Blacks and Whites and that
      different approaches may prove maximally effective in reducing heavy or problem
      drinking among the 2 groups.

PMID- 18729605
TI  - Psychological trauma and schizotypal personality disorder.
AB  - Two studies examined the relation between psychological trauma and schizotypal
      symptoms. In Study 1, in which 1,510 adults completed telephone interviews, both
      childhood maltreatment and the experience of an injury or life-threatening event
      were significantly associated with schizotypal symptoms. In Study 2, in which 303
      adults (oversampled for having elevated levels of schizotypal symptoms) completed
      extensive in-person assessments, both childhood maltreatment and meeting
      posttraumatic stress disorder (PTSD) Criterion A were significantly associated
      with schizotypal symptoms. The links between schizotypal symptoms and at least
      some forms of psychological trauma could not be fully accounted for by shared
      variance with antisocial and borderline personality disorders,
      absorption/dissociation, PTSD symptom severity, family history of psychotic
      disorder, or signs of neurodevelopmental disturbance (as indexed by minor
      physical anomalies and inconsistent hand use). Schizotypal symptoms were more
      strongly associated with childhood maltreatment among men than among women,
      whereas schizotypal symptoms were more strongly associated with PTSD Criterion A
      among women than among men. Finally, among men, the association between childhood
      maltreatment and schizotypal symptoms was moderated by signs of
      neurodevelopmental disturbance.

PMID- 18729606
TI  - Narrating emotional events in schizophrenia.
AB  - Research has indicated that schizophrenia patients report similar amounts of
      experienced emotion in response to emotional material compared with nonpatients.
      However, less is known about how schizophrenia patients describe and make sense
      of their emotional life events. We adopted a narrative approach to investigate
      schizophrenia patients' renderings of their emotional life experiences. In Study
      1, patients' (n=42) positive and negative narratives were similarly personal,
      tellable, engaged, and appropriate. However, negative narratives were less
      grammatically clear than positive narratives, and positive narratives were more
      likely to involve other people than negative narratives. In Study 2, emotional
      (positive and negative) narratives were less tellable and detached, yet more
      linear and social compared with neutral narratives for both schizophrenia
      patients (n=24) and healthy controls (n=19). However, patients' narratives about
      emotional life events were less appropriate to context and less linear, and
      patients' narratives, whether emotional or not, were less tellable and more
      detached compared with controls' narratives. Although schizophrenia patients are
      capable of recounting life events that trigger different emotions, the telling of
      these life events is fraught with difficulty.

PMID- 18729607
TI  - Searching for an environmental effect of parental alcoholism on offspring alcohol
      use disorder: a genetically informed study of children of alcoholics.
AB  - The children-of-twins design was used to isolate a potentially causal
      environmental impact of having an alcoholic parent on offspring alcohol use
      disorder, by an examination of whether the children of alcoholics were at a
      higher risk for alcohol use disorders than were the children of nonalcoholic
      parents, even after correlated familial factors were controlled. Participants
      were 1,224 male and female twins from 836 twin pairs selected from the Australian
      Twin Registry, 2,334 of the twins' 18-39-year-old offspring, and 983 spouses of
      the twins. Lifetime histories of Diagnostic and Statistical Manual of Mental
      Disorders (4th ed.) alcohol use disorders were obtained by structured,
      psychiatric, telephone interviews conducted individually with each of the family
      members. Comparisons of the offspring of twins who were discordant for alcoholism
      indicated that there was no longer a statistically significant difference between
      the children of alcoholics and the children of nonalcoholics after genetic and
      family environmental factors correlated with having an alcoholic parent were
      controlled. The results of this study suggest that the direct causal effect of
      being exposed to an alcoholic parent on offspring alcohol use disorder is modest
      at best.

PMID- 18729608
TI  - Classification of depressive disorders in the DSM-V: proposal for a two-dimension
      system.
AB  - The number of categories and specifiers for mood disorders has increased with
      each successive edition of the Diagnostic and Statistical Manual for Mental
      Disorders (DSM). Many of these categories and specifiers can be viewed as an
      effort to map the various permutations of severity and chronicity that
      characterize the depressive disorders. However, this has resulted in a system
      that (a) is unnecessarily complex and unwieldy, (b) has created problems with
      artificial distinctions between categories and artifactual comorbidity, and (c)
      at the same time obscures what may be more fundamental distinctions. A
      potentially useful and more parsimonious approach to capturing much of the
      heterogeneity of depressive disorders is to classify the depressive disorders
      along 2 dimensions, 1 reflecting severity and the other, chronicity.
      Considerations in the development of these dimensions are discussed, and a set of
      examples is presented. Although further research and discussion are needed to
      determine the optimal form of these dimensions, the next edition of the DSM
      should consider replacing many of the existing categories and specifiers for
      depressive disorders with the simpler approach of classifying depressive
      disorders using the 2 dimensions of severity and chronicity.

PMID- 18729610
TI  - On the hierarchical structure of mood and anxiety disorders: confirmatory
      evidence and elaboration of a model of temperament markers.
AB  - The authors examined D. Watson's (2005) proposed reconceptualization of the
      diagnostic categories for mood and anxiety disorders for the Diagnostic and
      Statistical Manual of Mental Disorders--Fifth Edition (DSM-V) and tested an
      elaboration of the 2-factor (positive and negative activation) model of
      underlying temperament markers that incorporates A. Tellegen, D. Watson, & L. A.
      Clark's (1999a, 1999b) higher-order dimension of happiness-unhappiness (or
      demoralization; see A. Tellegen et al., 2003). In Study 1, 502 undergraduate
      students completed several symptom measures of mood and anxiety disorders and the
      Minnesota Multiphasic Personality Inventory-2 (J. N. Butcher et al., 2001). Using
      confirmatory factor analysis, the authors replicated Watson's distress and fear
      disorder model. Path analyses showed that demoralization was a primary marker of
      distress disorders, whereas dysfunctional negative emotions was a primary marker
      of fear disorders. Low positive emotions was a specific marker of depression and
      social phobia. This 3-factor path model was associated with better fit than was a
      2-factor model excluding demoralization. In Study 2, the authors replicated the
      findings of Study 1 using data from an archival clinical sample of 636 Veterans
      Affairs hospital outpatients. The authors' findings provide evidence on the
      important role of demoralization in mood and anxiety disorders.

PMID- 18729609
TI  - How should we revise diagnostic criteria for substance use disorders in the DSM
      V?
AB  - This article reviews literature on the validity and performance characteristics
      of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV;
      American Psychiatric Association, 1994) diagnostic criteria for substance use
      disorders (SUDs) and recommends changes in these criteria that should be
      considered for the next edition of the DSM (DSM-V). Substantial data indicate
      that DSM-IV substance abuse and substance dependence are not distinct categories
      and that SUD criteria are best modeled as reflecting a unidimensional continuum
      of substance-problem severity. The conceptually and empirically problematic
      substance abuse diagnosis should be abandoned in the DSM-V, with substance
      dependence defined by a single set of criteria. Data also indicate that various
      individual SUD criteria should be revised, dropped, or considered for inclusion
      in the DSM-V. The DSM-V should provide a framework that allows the integration of
      categorical and dimensional approaches to diagnosis. Important areas for further
      research are noted.

PMID- 18729611
TI  - Cognitive inhibition and working memory in attention-deficit/hyperactivity
      disorder.
AB  - Studies of cognitive control in attention-deficit/hyperactivity disorder (ADHD)
      have emphasized the ability to suppress motor responses (i.e., behavioral
      inhibition) rather than the ability to actively suppress prepotent mental
      representations (i.e., cognitive inhibition). Further, working memory deficits
      are suspected in ADHD, yet their distinction from cognitive inhibition is
      unclear. Two hundred and eighty-eight adolescent and adult participants, 115 of
      whom met criteria for ADHD and 173 of whom were for non-ADHD comparison,
      completed a sentence processing task that required the suppression of an
      incorrect interpretation and a working memory task. The results failed to support
      cognitive inhibition problems in ADHD. Moreover, the ability to reanalyze
      sentences with a temporary misinterpretation was at least partially related to
      working memory performance. The results challenge a unitary inhibition problem in
      ADHD and suggest inhibition problems do not extend to cognitive suppression in
      this age range.

PMID- 18729612
TI  - Genetic effects explain the stability of psychopathic personality from mid- to
      late adolescence.
AB  - This study examined the importance of genetic and environmental influence for the
      stability of psychopathic personality between mid- and late adolescence. The
      target sample consisted of all 1,480 male and female twin pairs born in Sweden
      between 1985 and 1986. Psychopathic personality was measured with the Youth
      Psychopathic Traits Inventory (YPI; H. Andershed, M. Kerr, M. Stattin, & S.
      Levander, 2002) when the participants were 16 and 19 years old. Results showed
      that the 3 psychopathic personality dimensions were stable at different levels of
      analysis and linked to a stable higher order general factor (i.e., psychopathic
      personality factor). Genetic factors contributed substantially to the stability
      of this general higher order factor, whereas environmental factors were of little
      importance. However, the authors also found specific genetic stability in the
      Callous/unemotional and Impulsive/irresponsible dimension. Thus, the model
      provides evidence for etiologic generality and etiologic specificity for the
      stability of psychopathic personality between mid- and late adolescence.

PMID- 18729613
TI  - Does heightened affect make smoking cues more salient?
AB  - Negative affect (NA) states are robustly related to relapse. However, the
      mechanisms for this relationship are not well understood. Whereas most models
      have proposed that NA directly promotes lapsing, some models suggest that NA may
      promote lapses indirectly by increasing reactivity to smoking cues. This
      hypothesis was tested in secondary analyses of a study in which 248 smokers used
      ecological momentary assessment to self-monitor affective valence, smoking cues,
      and lapses during an attempt to quit smoking. The smoking cues the authors
      examined were others' smoking and consumption of alcohol or coffee. The odds of
      lapsing when exposed to smoking cues were compared across conditions of positive
      affect, neutral affect, and NA. Consistent main effects of affective valence were
      seen but not the hypothesized interaction. Indeed, analyses showed that the
      effect of cues was typically diminished under conditions of NA. No evidence was
      found to support the hypothesis that smoking cues and lapsing are more closely
      linked under NA conditions.

PMID- 18729614
TI  - Suicidal ideation and its recurrence in boys and men from early adolescence to
      early adulthood: an event history analysis.
AB  - Occurrence and recurrences of suicidal ideation (SI) were modeled among boys/men
      assessed annually from ages 12 to 29 years. Multiple-spell discrete-time event
      history analyses permitted (a) determination of whether risk for SI escalates
      with prior experiences of SI (spell effects), while (b) accounting for changes in
      risk with time (period effects) and (c) controlling for vulnerability factors.
      Self-reported SI (presence/absence in past week), depressive symptoms,
      alcohol/substance use, antisocial behavior, and official arrest records were
      collected annually from 205 boys recruited on the basis of community risk for
      delinquency. Parents' self-reported psychopathology and SES were collected in
      childhood. Period effects supported decreasing risk for SI over time. Spell and
      time-varying 1-year lagged substance use and depressive symptoms independently
      predicted increased risk for SI. Models involving SI with intent were explored.
      Consistent with interpersonal psychological theory, risk for young men's SI
      increases with past experience of SI, even with key propensities controlled.
      However, risk also decays over time. Targeting conditions that confer risk for SI
      is essential. Preventing and delaying SI occurrence and recurrence may represent
      independent mechanisms by which prevention efforts operate.

PMID- 18729615
TI  - Family-of-origin maltreatment, posttraumatic stress disorder symptoms, social
      information processing deficits, and relationship abuse perpetration.
AB  - In this study, the authors examined the interrelations among family-of-origin
      maltreatment variables, posttraumatic stress disorder (PTSD) symptoms, social
      information processing deficits, and male-to-female psychological and physical
      intimate relationship abuse perpetration in adulthood among a community sample of
      164 men and their partners. In bivariate analyses, higher family-of-origin
      childhood parental rejection was associated with the perpetration of
      psychological and physical abuse in adulthood, and childhood exposure to
      interparental violence was also associated with adult psychological abuse
      perpetration. Structural equation modeling analyses indicated that when childhood
      variables and other study variables were considered together, only childhood
      parental rejection was associated with the abuse perpetration outcomes, and these
      effects were indirect through PTSD symptoms and social information processing
      deficits. Results indicate a need for further investigation into the mechanisms
      accounting for the impact of early maltreatment on the development of abusive
      intimate relationship behavior.

PMID- 18729616
TI  - Affective instability: measuring a core feature of borderline personality
      disorder with ecological momentary assessment.
AB  - Ecological momentary assessment (EMA; Stone & Shiffman, 1994) was used to
      characterize and quantify a dynamic process--affective instability in borderline
      personality disorder (BPD). Sixty outpatients (34 with BPD and affective
      instability; 26 with current depressive disorder but not with BPD or affective
      instability) carried electronic diaries for approximately 1 month and were
      randomly prompted to rate their mood state up to 6 times a day. Results indicated
      that BPD patients (a) did not report significantly different mean levels of
      positive or negative affect; (b) displayed significantly more variability over
      time in their positive and negative affect scores; (c) demonstrated significantly
      more instability on successive scores (i.e., large changes) for hostility, fear,
      and sadness than did patients with depressive disorders; and (d) were more likely
      to report extreme changes across successive occasions (>or=90th percentile of
      change scores across participants) for hostility scores. Results illustrate
      different analytic approaches to quantifying variability and instability of
      affect based on intensive longitudinal data. Further, results suggest the promise
      of electronic diaries for collecting data from individuals in their natural
      environment for purposes of clinical research and assessment.

PMID- 18729617
TI  - The structure of distress following trauma: posttraumatic stress disorder, major
      depressive disorder, and generalized anxiety disorder.
AB  - The current report used confirmatory factor analysis to examine the latent
      structures of both key features and associated symptoms of three disorders that
      commonly develop following a traumatic event: posttraumatic stress disorder
      (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD).
      Participants were 228 motor-vehicle accident survivors who sought treatment for
      emotional difficulties. PTSD, MDD, and GAD were assessed with a combination of
      self-report and interview-based measures. The results of construct level analyses
      suggested that PTSD, MDD, and GAD are distinguishable but highly correlated
      disorders following a traumatic event. Symptom level analyses supported a model
      where the Reexperiencing, Avoidance, and Hypervigilance factors were subsumed
      under the PTSD construct. However, in this model the Dysphoria factor was a
      higher order construct correlated with the PTSD, MDD, and GAD factors, suggesting
      that the Dysphoria cluster may not be unique to PTSD. Diagnostic and theoretical
      implications of these results are discussed.

PMID- 18729619
TI  - Interpreting neutral faces as threatening is a default mode for socially anxious
      individuals.
AB  - The authors of the present study used an incidental learning paradigm to
      investigate the interpretation of neutral facial expressions in socially anxious
      individuals. Participants were asked to detect the location of a target following
      the presentation of a facial picture (i.e., cue). Unbeknownst to participants,
      the target location was contingent on the valence of the cue, and participants
      thus learned to associate different target locations with either positive or
      negative facial expressions. The authors subsequently used this learned
      association to assess interpretive biases. If socially anxious individuals
      interpret neutral faces in a negative manner, they should be faster to detect a
      target that appears in the location that is associated with negative face cues
      when the target is presented after a neutral face cue. The authors also assessed
      whether the anticipation of a feared situation influenced interpretive biases by
      comparing participants with and without a speech threat on this task. Results
      indicate that socially anxious individuals are characterized by an interpretive
      bias regardless of the threat manipulation. In contrast, nonanxious individuals
      interpreted neutral faces in a negative manner only when they were in the threat
      condition.

PMID- 18729618
TI  - Developmental influences on interpersonal stress generation in depressed youth.
AB  - This research tested the hypothesis that the transition through adolescence,
      particularly undergoing puberty early relative to one's peers, would amplify the
      effect of depression on the subsequent generation of interpersonal stress. This
      hypothesis was examined in 158 youth (M age=12.39 years, SD=1.21) using
      semistructured interviews of depression and life stress. Three indexes of
      development--chronological age, pubertal status, and pubertal timing--were
      examined as possible moderators of the stress-generation effect. As anticipated,
      depression predicted interpersonal stress generation in early-maturing but not
      late-maturing youth. These findings provide an important developmental context
      for theory and research on stress generation.

PMID- 18729620
TI  - Interidentity memory transfer in dissociative identity disorder.
AB  - Controversy surrounding dissociative identity disorder (DID) has focused on
      conflicting findings regarding the validity and nature of interidentity amnesia,
      illustrating the need for objective methods of examining amnesia that can
      discriminate between explicit and implicit memory transfer. In the present study,
      the authors used a cross-modal manipulation designed to mitigate implicit memory
      effects. Explicit memory transfer between identities was examined in 7 DID
      participants and 34 matched control participants. After words were presented to
      one identity auditorily, the authors tested another identity for memory of those
      words in the visual modality using an exclusion paradigm. Despite self-reported
      interidentity amnesia, memory for experimental stimuli transferred between
      identities. DID patients showed no superior ability to compartmentalize
      information, as would be expected with interidentity amnesia. The cross-modal
      nature of the test makes it unlikely that memory transfer was implicit. These
      findings demonstrate that subjective reports of interidentity amnesia are not
      necessarily corroborated by objective tests of explicit memory transfer.

PMID- 18729621
TI  - An alternative hierarchical organization of the mental disorders of the DSM-IV.
AB  - With the approaching publication of the fifth edition of the Diagnostic and
      Statistical Manual of Mental Disorders (DSM), alternative organizations of the
      DSM (4th ed.; DSM-IV; American Psychiatric Association, 1994) categories have
      been proposed. This article compares several published alternative organizations
      to clinicians' organization of the DSM-IV categories. As demonstrations of their
      organization of DSM-IV categories, psychologists and psychiatrists sorted 66 DSM
      IV diagnostic categories into groups of similar diagnoses and then made
      progressively larger and smaller groups of diagnoses or placed similar groups
      next to each other on a table. Hierarchical agglomerative data analysis of
      clinicians' individual sortings showed that clinicians retained many lower level
      DSM-IV categories (e.g., anxiety disorders, mood disorders), but not the higher
      level DSM-IV categories (e.g., Axis I vs. Axis II). Instead, at the highest
      hierarchical level, clinicians' categories resembled the structure of the first
      edition of the DSM (American Psychiatric Association, 1952), which followed
      clinicians' diagnostic decision-making scheme, dividing mental disorders into
      organic versus nonorganic and then psychotic versus neurotic disorders. At
      minimum, these data suggest a DSM organization that makes sense to clinicians.

PMID- 18729623
TI  - The psychology of psychiatric genetics: evidence that positive emotions in
      females moderate genetic sensitivity to social stress associated with the BDNF
      Val-sup-6-sup-6Met polymorphism.
AB  - Previous work indicated protective effects of positive emotions on genetically
      influenced stress sensitivity. Given the fact that expression of brain-derived
      neurotrophic-factor (BDNF) is associated with stress-induced behavioral changes,
      it was hypothesized that the BDNF Val-sup-6-sup-6Met genotype may mediate genetic
      effects on stress sensitivity, conditional on the level of concurrent positive
      emotions. Subjects (n=446) participated in a momentary assessment study,
      collecting appraisals of stress and affect in the flow of daily life. Multilevel
      regression analyses examined moderation of daily life stress-induced negative
      affect (NA) by BDNF genotype, and to what degree this was conditional on
      concurrent positive emotions. Results showed that heterozygous BDNF "Met"
      carriers exhibited an increased NA response to social stress compared with
      "Val/Val" subjects. Positive emotions at the time of the stressor decreased BDNF
      genetic moderation of the NA response to social stress in a dose-response
      fashion. This effect was most pronounced in BDNF Met carriers. Thus, the impact
      of BDNF genotype on stress sensitivity is conditional on the experience of
      positive emotions. Interdisciplinary research in psychology and psychiatric
      genetics may lead to the improvement of treatment choices in stress-related
      disorders.

PMID- 18729624
TI  - Taxometric analyses of borderline personality features in a large-scale male and
      female offender sample.
AB  - Few studies to date have examined the extent to which borderline personality
      features are best construed as representing an underlying dimension or a discrete
      class or taxon. The authors conducted taxometric analyses using a large-scale
      sample of male (n=787) and female (n=368) prison inmates who had completed the
      Personality Assessment Inventory (L. C. Morey, 2007). Analyses based on the 4
      subscales of the Borderline Features Scale offered compelling support for a
      dimensional structure in both the full sample and the female subsample--even
      after controlling for the potentially confounding effects of negative response
      distortion. Theoretical and pragmatic implications of these findings are
      reviewed.

PMID- 18729625
TI  - Restriction of working memory capacity during worry.
AB  - The authors report the first direct assessment of working memory capacity when
      people engage in worry. High and low worriers performed a random key-press task
      while thinking about a current worry or a positive personally relevant topic.
      High (but not low) worriers showed more evidence of restricted capacity during
      worry than when thinking about a positive topic. These findings suggest that high
      worriers have less residual working memory capacity when worrying than when
      thinking about other topics and, thus, have fewer attentional resources available
      to redirect their thoughts away from worry.

PMID- 18729626
TI  - Age-dependent phenotypic characteristics of a triple transgenic mouse model of
      Alzheimer disease.
AB  - The triple-transgenic mouse line (3 x Tg-AD) harboring PS1M146V, APPSwe, and
      taup301L transgenes represents the only transgenic model for Alzheimer's disease
      (AD) to date capturing both beta-amyloid and tau neuropathology. The present
      study provides an extensive behavioral characterization of the 3 x Tg-AD mouse
      line, evaluating the emergence of noncognitive and cognitive AD-like symptoms at
      two ages corresponding to the early (6-7 months) and advanced (12-13 months)
      stages of AD-pathology. Enhanced responsiveness to aversive stimulation was
      detected in mutant mice at both ages: the 3 x Tg-AD genotype enhanced acoustic
      startle response and facilitated performance in the cued-version of the water
      maze. These noncognitive phenotypes were accompanied by hyperactivity and reduced
      locomotor habituation in the open field at the older age. Signs of cognitive
      aberrations were also detected at both ages, but they were limited to associative
      learning. The present study suggests that this popular transgenic mouse model of
      AD has clear phenotypes beyond the cognitive domain, and their potential
      relationship to the cognitive phenotypes should be further explored.

PMID- 18729627
TI  - Behavioral profile of a heterozygous mutant mouse model for EGF-like domain
      neuregulin 1.
AB  - Human genetic studies have demonstrated that the neuregulin 1 gene (NRG1) is
      involved in the development of schizophrenia. Alternative splicing of NRG1
      results in at least 15 distinct isoforms and all contain an extracellular
      epidermal growth factor (EGF)-like domain, which is sufficient for Nrg1's
      biological activity. Here, we characterize a heterozygous mutant model for mouse
      EGF-like domain neuregulin 1 (Nrg1) regarding schizophrenia-related behavioral
      domains. A comprehensive, multitiered phenotyping strategy was used to
      investigate locomotion, exploration, anxiety-related behaviors, and sensorimotor
      gating. Nrg1 mutant mice exhibited a hyper-locomotive phenotype and an improved
      ability to habituate to a new environment. Extensive analysis of anxiety-related
      behaviors revealed a wild type-like phenotype in this domain. However, a moderate
      impairment in sensorimotor gating was found after pharmacological challenge using
      psychoactive substances. Our study adds to the increasing behavioral data
      available from a variety of animal models for Nrg1 isoforms. We suggest a
      standardized and comprehensive behavioral phenotyping approach to distinguish
      between the different models and to clarify their relevance for schizophrenia
      research. Future behavioral investigations will focus on the negative and
      cognitive symptoms of schizophrenia.

PMID- 18729629
TI  - Differential genetic regulation of motor activity and anxiety-related behaviors
      in mice using an automated home cage task.
AB  - Traditional behavioral tests, such as the open field test, measure an animal's
      responsiveness to a novel environment. However, it is generally difficult to
      assess whether the behavioral response obtained from these tests relates to the
      expression level of motor activity and/or to avoidance of anxiogenic areas. Here,
      an automated home cage environment for mice was designed to obtain independent
      measures of motor activity levels and of sheltered feeding preference during
      three consecutive days. Chronic treatment with the anxiolytic drug
      chlordiazepoxide (5 and 10 mg/kg/day) in C57BL/6J mice reduced sheltered feeding
      preference without altering motor activity levels. Furthermore, two distinct
      chromosome substitution strains, derived from C57BL/6J (host strain) and A/J
      (donor strain) inbred strains, expressed either increased sheltering preference
      in females (chromosome 15) or reduced motor activity levels in females and males
      (chromosome 1) when compared to C57BL/6J. Longitudinal behavioral monitoring
      revealed that these phenotypic differences maintained after adaptation to the
      home cage. Thus, by using new automated behavioral phenotyping approaches,
      behavior can be dissociated into distinct behavioral domains (e.g., anxiety
      related and motor activity domains) with different underlying genetic origin and
      pharmacological responsiveness.

PMID- 18729628
TI  - Narp regulates long-term aversive effects of morphine withdrawal.
AB  - Although long-lasting effects of drug withdrawal are thought to play a key role
      in motivating continued drug use, the mechanisms mediating this type of drug
      induced plasticity are unclear. Because Narp is an immediate early gene product
      that is secreted at synaptic sites and binds to alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptors, it has been implicated in mediating
      enduring forms of synaptic plasticity. In previous studies, the authors found
      that Narp is selectively induced by morphine withdrawal in the extended amygdala,
      a group of limbic nuclei that mediate aversive behavioral responses. Accordingly,
      in this study, the authors evaluate whether long-term aversive effects of
      morphine withdrawal are altered in Narp knockout (KO) mice. The authors found
      that acute physical signs of morphine withdrawal are unaffected by Narp deletion.
      However, Narp KO mice acquire and sustain more aversive responses to the
      environment conditioned with morphine withdrawal than do wild type (WT) controls.
      Paradoxically, Narp KO mice undergo accelerated extinction of this heightened
      aversive response. Taken together, these studies suggest that Narp modulates both
      acquisition and extinction of aversive responses to morphine withdrawal and,
      therefore, may regulate plasticity processes underlying drug addiction.

PMID- 18729631
TI  - Data mining in a behavioral test detects early symptoms in a model of amyotrophic
      lateral sclerosis.
AB  - "What's wrong with my genetically engineered animal?" is a common yet often
      difficult to answer question in behavioral phenotyping. We present here a method
      termed Pattern Array for mining movement patterns and isolating those that best
      capture an effect of a genetic manipulation. We demonstrate the method by
      searching for early motor symptoms in the open-field behavior of SOD1 mutant
      rats, an animal model of amyotrophic lateral sclerosis. Pattern Array was able to
      identify a unique motor pattern that differentiated the SOD1 mutants from the
      wild-type controls 2 months before disease onset. This pattern included heavy
      braking while moving near the arena wall but turning away from it. SOD1 mutants
      performed this pattern significantly less than wild-type controls in 2
      independent data sets. At such early age the SOD1 mutants could not be
      differentiated from the controls by standard behavioral measures or by subjective
      observation. The early discovered symptom may enable investigators to test
      therapies aimed for intervention rather than remediation. Our results demonstrate
      the feasibility and potential of detecting subtle behavioral effects using data
      mining strategies.

PMID- 18729632
TI  - Sexually dimorphic enhancement by estradiol of male urinary odor detection
      thresholds in mice.
AB  - We asked whether sex and adult estrogen exposure influence the detection
      thresholds for urinary odors used by mice to guide their social behaviors.
      Gonadectomized (GDX) male and female mice were trained on a two-choice food
      motivated task to determine detection thresholds for male urinary odors. There
      was no significant sex difference in the detection of these odors by GDX subjects
      without hormone replacement. However, during treatment with estradiol benzoate
      (EB), GDX females, but not GDX males, showed an enhanced ability to detect these
      odors. To investigate a possible mechanism for this effect, the authors measured
      GDX females' odor-sampling behavior (sniffing) by monitoring intranasal pressure
      transients during performance of the urinary odor detection task with and without
      EB treatment. Under both hormone conditions, females decreased their sniffing
      frequency as the urinary odor concentration decreased, with this decrease being
      significantly greater while GDX females received EB. Thus, estradiol enhanced
      detection thresholds for male urine in a sex-specific manner, and this enhanced
      sensitivity in females was correlated with altered odor-sampling behavior.

PMID- 18729634
TI  - A possible role for protein synthesis, extracellular signal-regulated kinase, and
      brain-derived neurotrophic factor in long-term spatial memory retention in the
      water maze.
AB  - Hippocampal protein synthesis is dependent upon a number of different molecular
      and cellular mechanisms that act together to make previously labile memories more
      stable and resistant to disruption. Both brain-derived neurotrophic factor (BDNF)
      and extracellular signal-regulated kinase (ERK) are known to play an important
      role in protein synthesis-dependent memory consolidation, via the mitogen
      activated protein-kinase (MAP-K) signaling pathway during the transcription phase
      of protein synthesis. The current study investigates the influence of protein
      synthesis inhibition (PSI) by cycloheximide on spatial learning and memory. In an
      initial experiment, the authors utilized two doses of cycloheximide (0.5 mg/kg
      and 1.0 mg/kg, intraperitoneally) to determine the dose at which long-term (>24
      hours) memories are impaired. A second experiment was designed to investigate the
      effect of PSI on the formation of cue-platform associations in the watermaze, and
      on BDNF and ERK expression in the hippocampus. At the higher dose (1.0 mg/kg)
      cycloheximide resulted in impaired retention of the water maze. BDNF and ERK
      expression was also down-regulated in animals injected with this dose of
      cycloheximide. Our results demonstrate a role of protein synthesis in spatial
      memory retention, along with a possible relationship between protein synthesis
      and hippocampal BDNF/ERK expression.

PMID- 18729633
TI  - Effects of chronic estradiol treatment on delayed spatial alternation and
      differential reinforcement of low rates of responding.
AB  - Estrogens have been shown to both enhance and impair cognitive function depending
      on several factors, including regimen of hormone treatment, age of subject, and
      task attributes. In rodent models, estradiol tends to enhance spatial learning
      and impair response or cued learning, but effects on executive functions are less
      well-studied. In this experiment, spatial working memory and response inhibition
      were tested using delayed spatial alternation (DSA) and differential
      reinforcement of low rates of responding (DRL) tasks in ovariectomized rats that
      were given chronic estradiol via Silastic implants resulting in serum estradiol
      concentrations of 86.2 +/- 8.2 (SEM) pg/ml. Rats were tested for 25 days DSA with
      variable delays of 0, 3, 6, 9, and 18 seconds between lever presentations,
      followed by 30 days on a DRL-15s operant schedule. Estradiol-replaced rats showed
      a significantly lower proportion of correct responses on the DSA task compared to
      vehicle-implanted ovariectomized animals. On DRL, estradiol-treated rats showed a
      lower ratio of reinforced to nonreinforced presses. These data suggest that
      chronic estrogen exposure may impair rats' abilities on measures of executive
      function including working memory and response inhibition.

PMID- 18729635
TI  - Noradrenergic neuromodulation in the olfactory bulb modulates odor habituation
      and spontaneous discrimination.
AB  - Noradrenergic projections from the locus coeruleus (LC) project to the olfactory
      bulb (OB), a cortical structure implicated in odor learning and perceptual
      differentiation among similar odorants. The authors tested the role of OB
      noradrenaline (NA) in short-term olfactory memory using an animal model of LC
      degeneration coupled with intrabulbar infusions of NA. Specifically, the authors
      lesioned cortical noradrenergic fibers in mice with the noradrenergic neurotoxin
      N-Ethyl-N-(2-chloroethyl)-2-bromobenzylamine hydrochloride (DSP4) and measured
      the effects on an olfactory habituation/spontaneous discrimination task. DSP4
      treated mice failed to habituate to repeated odor presentations, indicating that
      they could not remember odors over the 5-min intertrial interval. The authors
      then infused NA bilaterally into the OBs of both DSP4-treated and nonlesioned
      control animals at two concentrations (10(-3)M and 10(-5)M, 2 microl/side). In
      DSP4-treated animals, NA administration at either concentration restored normal
      habituation and spontaneous discrimination performance, indicating that
      noradrenergic neuromodulation mediates these aspects of perceptual learning and
      that its efficacy does not require activity-dependent local regulation of NA
      release. Functional OB learning mechanisms may be necessary for normal odor
      recognition and differentiation among physically similar odorants.

PMID- 18729637
TI  - Prefrontal control of trace eyeblink conditioning in rabbits: role in retrieval
      of the CR?
AB  - Rabbits (Oryctolagus cuniculus) were trained on a trace eyeblink (EB)
      conditioning task to a criterion of 10 consecutive EB conditioned responses
      (CRs). One week later, ibotenic acid or sham lesions were made in the mPFC
      centered on the prelimbic region (Brodmann's area 32) or the cingulate cortex
      (Brodmann's area 24). Following a 1-week postoperative recovery period, all
      animals were retrained for 4 consecutive days using the same parameters as during
      acquisition, given 1 week off, and retrained for another 4 days. Mean EB
      conditioning deficits in the group with area 32 lesions occurred on the first and
      second days of each retraining period. However, by the third and fourth days of
      retraining, these lesioned animals were performing at a level comparable to that
      of the sham group. Lesions of area 24 did not produce deficits at either
      retesting period. These findings were interpreted to indicate that area 32, but
      not area 24, is involved in retrieval processes, rather than consolidation or
      storage, in that the animals were impaired at both retesting times, but were able
      to relearn the task.

PMID- 18729636
TI  - Landmark control and updating of self-movement cues are largely maintained in
      head direction cells after lesions of the posterior parietal cortex.
AB  - Head direction (HD) cells discharge as a function of the rat's directional
      orientation with respect to its environment. Because animals with posterior
      parietal cortex (PPC) lesions exhibit spatial and navigational deficits, and the
      PPC is indirectly connected to areas containing HD cells, we determined the
      effects of bilateral PPC lesions on HD cells recorded in the anterodorsal
      thalamus. HD cells from lesioned animals had similar firing properties compared
      to controls and their preferred firing directions shifted a corresponding amount
      following rotation of the major visual landmark. Because animals were not exposed
      to the visual landmark until after surgical recovery, these results provide
      evidence that the PPC is not necessary for visual landmark control or the
      establishment of landmark stability. Further, cells from lesioned animals
      maintained a stable preferred firing direction when they foraged in the dark and
      were only slightly less stable than controls when they self-locomoted into a
      novel enclosure. These findings suggest that PPC does not play a major role in
      the use of landmark and self-movement cues in updating the HD cell signal, or in
      its generation.

PMID- 18729638
TI  - Early social deprivation induces disturbed social communication and violent
      aggression in adulthood.
AB  - Disturbed social relations during childhood (e.g., social neglect) often lead to
      aggression-related psychopathologies in adulthood. Social isolation also
      increased aggressiveness in laboratory animals. Here the authors show in rats,
      that social isolation from weaning not only increases the level of
      aggressiveness, but results in abnormal attack patterns and deficits in social
      communication. In socially deprived rats, the share of attacks aimed at
      vulnerable body parts of opponents (head, throat, and belly) dramatically
      increased and the attack/threat ratio was shifted toward attacks, suggesting a
      decrease in intention signaling. Moreover, a Multiple Regression Analysis showed
      that the nonassociation of attacks with offensive threats predicted the
      occurrence of vulnerable attacks with 81.1% accuracy. The authors suggest that
      the social deprivation-induced abnormal aggression models the aggression-related
      problems resulting from early social neglect in humans, and studies on its brain
      mechanisms may increase our understanding of the mechanisms underlying
      psychopathologies resulting from early social problems.

PMID- 18729639
TI  - Perinatal inhibition of aromatization enhances the reward value of sex.
AB  - Paced mating reduces the aversive properties and increases the positive
      characteristics of mating, inducing a reward state. Pacing is able to induce
      conditioned place preference (CPP), whereas nonpaced mating does not. The authors
      hypothesized that the aversive properties of mating are caused by androgens from
      adjacent males or from the mother during fetal life. To test whether
      aromatization of androgens induces the aversive properties of mating, female rats
      were treated perinatally with 1,4,6-androstatriene-3, 17-dione (ATD) to inhibit
      aromatization. When adults, these females were ovariectomized and hormonally
      primed to evaluate CPP after paced and nonpaced mating. During paced mating,
      control females showed higher return latencies after ejaculation, whereas ATD
      treated females did not show a similar increase. In CPP tests, both paced and
      nonpaced mating induced a reward state in ATD-treated females, whereas only paced
      mating induced a reward state in control females. These results show that the
      perinatal inhibition of aromatization enhances the rewarding properties of
      mating, suggesting that estradiol induced the aversive properties of mating
      and/or modified the perinatal organization of the neuronal pathways in females.

PMID- 18729640
TI  - Dependence of adolescent novelty-seeking behavior on response phenotype and
      effects of apparatus scaling.
AB  - Adult rats have been phenotyped as high (HRs) or low (LRs) responders to novelty,
      the former associated with high-risk behaviors. Data indicating that adolescent
      rodents exhibit increased novelty-seeking relative to adults are equivocal, and
      phenotypic variations in adolescent novel stimulus reactivity are unknown. To
      determine whether novelty-seeking differs between adolescent and adult rats,
      reflecting phenotypic variations within each age, activities in an inescapable
      novel environment and novel object exploration were measured. Adolescents moved
      further, faster, and more continuously than adults, and exhibited a greater
      variability and range of activity in the novel environment. Both adolescent and
      adult LRs habituated to the environment by the second trial, but HRs maintained
      increased activity throughout 8 trials. In the free-choice paradigm, adolescents
      approached the novel object more frequently and spent more time in proximity to
      the object than adults. Similar results were obtained using arenas and objects of
      the same size or scaled to animal size. Results confirm that novelty-seeking by
      adolescents is greater than by adults, a behavior attributed primarily to the
      response magnitude exhibited by adolescents with the HR phenotype.

PMID- 18729642
TI  - On the influence of baseline startle reactivity on the indexation of prepulse
      inhibition.
AB  - Prepulse inhibition (PPI) of the startle reflex refers to the reduction of the
      reflexive startle response to an intense pulse stimulus when its presentation is
      shortly preceded by a weak prepulse stimulus. PPI is considered as a cross
      species translational model of sensorimotor gating, and deficient PPI has been
      reported in a number of neuropsychiatric disorders. Although a part of the
      literature is based on the assumption that PPI is independent of the baseline
      startle reaction, there is accumulating evidence (Csomor et al., 2006; Sandner &
      Canal, 2007; Yee, Chang, Pietropaolo, & Feldon, 2005) that argues against such an
      independency. The authors systematically investigated whether PPI indexed as
      percentage or difference score is dependent on the magnitude of baseline startle
      reactivity in healthy human volunteers and in C57BL/6 mice. The results revealed
      that both indexations of PPI were affected by the magnitude of the baseline
      startle. The authors highlight the pitfalls of different methods to index PPI,
      especially when startle reactivity differs considerably between groups under
      comparison, and offer practical recommendations to satisfactorily deal with such
      baseline differences.

PMID- 18729641
TI  - Aggressive behaviors in adult SF-1 knockout mice that are not exposed to gonadal
      steroids during development.
AB  - Sex hormones are a major factor responsible for the development of sex
      differences. Steroidogenic factor 1 (SF-1) is a key regulator of gonadal and
      adrenal development, and SF-1 knockout mice (SF-1 KO) are born without gonads and
      adrenal glands. Consequently, these mice are not exposed to gonadal sex steroids.
      SF-1 KO pups die shortly after birth due to adrenal deficiency. In the present
      study, SF-1 KO mice were rescued by neonatal corticosteroid injections followed
      by adrenal transplantations on day 7-8 postnatally. Control mice received
      corticosteroid injections and were gonadectomized prior to puberty. Mice were
      observed interacting with ovariectomized hormone primed females and gonad-intact
      males. In the absence of sex steroid replacement, adult SF-1 KO mice were
      significantly more aggressive than control mice in tests with stimulus females.
      After testosterone treatment, control males displayed significantly more
      aggression towards male intruders than control female mice, or male and female SF
      1 KO mice, suggesting a developmental role of gonadal hormones in the expression
      of aggressive behavior and affirming SF-1 KO mice as a behavioral model to
      investigate affects of fetal gonad deficiency.

PMID- 18729643
TI  - COMT genetic variation affects fear processing: psychophysiological evidence.
AB  - Emotional dysregulation is a core characteristic of many psychiatric diseases,
      including the anxiety disorders. Although heritable influences account for a
      significant degree of variation in risk for such disorders, relatively few
      candidate susceptibility factors have been identified. A coding variant in one
      such gene, encoding the dopamine catabolic enzyme catechol-O-methyltransferase
      (COMT Val158Met), has previously been associated with anxiety and with anxiety
      related temperament and altered neural responses to affective stimuli in healthy
      individuals. In 96 healthy women recruited from a sample of 800 participants
      according to genotype, the authors tested for an association between the
      DRD2/ANKK1 Taq Ia, the COMT Val158Met, and a psychophysiological measure of
      emotion processing, the acoustic affective startle reflex modulation (ASRM)
      paradigm, and found that COMT genotype significantly affected startle reflex
      modulation by aversive stimuli, with Met158 homozygotes exhibiting a markedly
      potentiated startle reflex compared with Val158 carriers. A trait measure of
      anxiety (Gray's Behavioral Inhibition System; J. A. Gray & N. McNaughton, 2000)
      was also associated with ASRM. The functional polymorphism in the dopamine D2
      receptor (DRD2/ANKK1 Taq Ia) had no effect on startle modulation. The findings
      support prior genetic and neuroimaging associations of the COMT 158Met allele to
      affective psychopathology and alterations in neural systems for emotional arousal
      and regulation.

PMID- 18729644
TI  - How similar are motor imagery and movement?
AB  - It has been suggested that motor imagery (MI) has the basic components of real
      motion. This possibility was tested here in 17 healthy volunteers studied while
      performing or imaging a fast sequence of finger movements of progressive
      complexity, a fast and precise extension of the arm to touch a small circle with
      the tip of a pencil, a periodic repetitive flexion-extension of the index finger
      at a specified rate, and a velocity-regulated continuous rotary movement of the
      right hand. Motor sequences of 4 to 5 fingers showed a real-virtual congruency
      similar to that previously reported with other equivalent tests, but it decreased
      in the simplest sequences performed with 1 to 2 fingers. A more marked decrease
      of real-virtual congruency was found in the experimental paradigm aimed at
      producing movements with a pre-specified velocity, which was low for rhythmic
      movements of the index finger and practically absent in the continuous rotary
      movements of the hand. Present data show that the ability of MI to produce
      "realistic" simulations of motion is not the same for all motor tasks.

PMID- 18729645
TI  - Functional cortico-muscular coupling during upright standing in athletes and
      nonathletes: a coherence electroencephalographic-electromyographic study.
AB  - We tested the hypothesis that functional cortico-muscular coupling of brain
      rhythms is implied in the control of lower limb muscles for upright standing.
      Electroencephalographic (EEG; Be-plus Eb-Neuro) and electromyographic (EMG) data
      were recorded in 18 fencing and 19 karate elite athletes, 14 karate amateurs, and
      9 non-athletes, during quiet upright standing with open and closed eyes
      conditions. Cortico-muscular coupling was evaluated by computing EEG-EMG spectral
      coherence and directed transfer function (DTF). Body sway area did not differ
      among the groups. In non-athletes, the EEG-EMG coherence (gastrocnemius
      lateralis) at centro-parietal and parasylvian alpha rhythms (about 8-12 Hz) was
      higher during the open than closed eyes condition. This was not true in the elite
      athletes. At the same alpha rhythms, the sport amateurs presented values halfway
      between the non-athletes and elite athletes. Finally, the DTF was higher for
      cortico-muscular than muscular-cortical direction. These results suggest that
      visual information affects cortico-muscular coherence at 8-12 Hz in non-athletes
      and amateur athletes but not in elite athletes. In elite athletes, this might be
      due to a long training for the control of equilibrium based on proprioceptive and
      tactile inputs.

PMID- 18729646
TI  - Sleep inertia varies with circadian phase and sleep stage in older adults.
AB  - The purpose of our analysis was to determine if older adults show sleep inertia
      effects on performance at scheduled wake time, and whether these effects depend
      on circadian phase or sleep stage at awakening. Using the Digit Symbol
      Substitution Test, effects of sleep inertia on performance were assessed over the
      first 30 min after wake time on baseline days and when sleep was scheduled at
      different circadian phases. Mixed model analyses revealed that performance
      improved as time awake increased; that beginning levels of performance were
      poorest when wake time was scheduled to occur during the biological night; and
      that effects of sleep inertia on performance during the biological night were
      greater when awaking from non-REM (NREM) sleep than from REM sleep. Based on our
      current understanding of sleep inertia effects in young subjects, and previous
      reports that older subjects awaken at an earlier circadian phase and are more
      likely to have their final awakening from NREM sleep than younger adults, our
      findings suggest older adults may be more vulnerable to sleep inertia effects
      than young adults.

PMID- 18729647
TI  - Deprivation selectively modulates brain potentials to food pictures.
AB  - Event-related brain potentials (ERPs) were used to examine whether the processing
      of food pictures is selectively modulated by changes in the motivational state of
      the observer. Sixteen healthy male volunteers were tested twice 1 week apart,
      either after 24 hr of food deprivation or after normal food intake. ERPs were
      measured while participants viewed appetitive food pictures as well as standard
      emotional and neutral control pictures. Results show that the ERPs to food
      pictures in a hungry, rather than satiated, state were associated with enlarged
      positive potentials over posterior sensor sites in a time window of 170-310 ms
      poststimulus. Minimum-norm analysis suggests the enhanced processing of food cues
      primarily in occipito-temporo-parietal regions. In contrast, processing of
      standard emotional and neutral pictures was not modulated by food deprivation.
      Considered from the perspective of motivated attention, the selective change of
      food cue processing may reflect a state-dependent change in stimulus salience.

PMID- 18729648
TI  - Exercise is associated with reduction in the anxiogenic effect of mCPP on
      acoustic startle.
AB  - Voluntary exercise has been associated with reduced anxiety across several animal
      models. Manipulation of central 5-HT can alter anxiety-like behaviors and
      administration of the 5-HT agonist metachlorophenylpiperazine (mCPP) increases
      anxiety in rodents and humans. To examine whether the anxiolytic effect of
      exercise is associated with an alteration in 5-HT systems, we examined the
      anxiogenic effect of mCPP in exercising and nonexercising mice. C57BL/6J mice
      were given 2 weeks of free access to either a functioning or nonfunctioning
      running wheel. Mice were then tested for acoustic startle following systemic
      injection of either 0, 0.1, 0.3, or 1 mg/kg of mCPP. Consistent with its
      anxiogenic properties, mCPP produced a dose-dependent increase in acoustic
      startle in nonexercising mice. However, this anxiogenic effect was blunted in
      exercising mice. These findings suggest that exercise may help to reduce anxiety
      by altering 5-HT systems, perhaps by down-regulating postsynaptic 5HT 2B/2C
      receptors.

PMID- 18729649
TI  - Galanin stimulation of feeding is blocked by the addition of a response
      requirement.
AB  - Administration of the neuropeptide galanin increases food intake in laboratory
      rats and mice, however this increase has only been observed under conditions of
      free-feeding. As there is a growing distinction between consummatory and
      instrumental behavior, we assessed whether galanin would differentially affect
      food consumption when food was freely available or when the same food was
      response-contingent. We also tested whether food restriction would interact with
      galanin's effect on food consumption in either condition. As in previous studies,
      galanin significantly increased food consumption under free access conditions.
      However, when food was contingent upon lever-pressing, galanin had no such
      stimulatory effect. Food-restriction increased basal feeding levels in both tasks
      but there was no interaction between food restriction and free or response
      contingent food intake. These results demonstrate that galanin-induced feeding
      stimulation is limited to conditions of free access and support the theoretical
      distinction between consummatory and instrumental behavior.

PMID- 18729651
TI  - Acoustic interaction in animal groups: signaling in noisy and social contexts.
AB  - It has long been known that individuals of many species vocally communicate with
      one another in noisy environments and in rich contexts of social interaction. It
      has recently become clear that researchers interested in understanding acoustic
      communication in animal groups must study vocal signaling in these noisy and
      socially complex settings. Furthermore, recent methodological advances have made
      it increasingly clear that the authors can tackle these more complex questions
      effectively. The articles in this Special Issue stem from a Symposium held at the
      June 2006 meeting of the Acoustical Society of America, and illustrate some of
      the taxonomic and methodological diversity in studies aimed at understanding how
      acoustic communication functions in social grouping. This introduction to the
      Special Issue provides a brief overview of the articles and key ideas in this
      field of inquiry, and suggests some future directions to take the field to help
      us understand how social pressures in animal groups may influence, and be
      influenced by, acoustic signals.

PMID- 18729653
TI  - Discrimination of acoustic communication signals by grasshoppers (Chorthippus
      biguttulus): temporal resolution, temporal integration, and the impact of
      intrinsic noise.
AB  - A characteristic feature of hearing systems is their ability to resolve both fast
      and subtle amplitude modulations of acoustic signals. This applies also to
      grasshoppers, which for mate identification rely mainly on the characteristic
      temporal patterns of their communication signals. Usually the signals arriving at
      a receiver are contaminated by various kinds of noise. In addition to extrinsic
      noise, intrinsic noise caused by stochastic processes within the nervous system
      contributes to making signal recognition a difficult task. The authors asked to
      what degree intrinsic noise affects temporal resolution and, particularly, the
      discrimination of similar acoustic signals. This study aims at exploring the
      neuronal basis for sexual selection, which depends on exploiting subtle
      differences between basically similar signals. Applying a metric, by which the
      similarities of spike trains can be assessed, the authors investigated how well
      the communication signals of different individuals of the same species could be
      discriminated and correctly classified based on the responses of auditory
      neurons. This spike train metric yields clues to the optimal temporal resolution
      with which spike trains should be evaluated.

PMID- 18729654
TI  - Assessment of distance to potential mates by female barking treefrogs (Hyla
      gratiosa).
AB  - This study investigated the cues used by female barking treefrogs, Hyla gratiosa,
      to assess distances to potential mates. Eight-speaker playback experiments were
      used to demonstrate that distance affects female choice in complex acoustic
      environments and to test 3 possible cues that females might use to assess
      distance: (a) degradation in spectral and temporal cues of calls, (b) relative
      call amplitude at the female's location, and (c) the rate at which the amplitude
      of calls increases as a female approaches a calling male. All 3 hypotheses were
      refuted, suggesting that females use a more complex mechanism, such as
      triangulation, to assess distance. Females preferred speakers with greater source
      amplitudes even when they had to travel further to reach those speakers.
      Determination of source amplitude is possible only if females can assess
      independently both the distance to sound sources and the amplitude of calls at
      the females' location. Hence, anuran amphibians may possess greater cognitive
      abilities than are generally attributed to them.

PMID- 18729652
TI  - The cocktail party problem: what is it? How can it be solved? And why should
      animal behaviorists study it?
AB  - Animals often use acoustic signals to communicate in groups or social
      aggregations in which multiple individuals signal within a receiver's hearing
      range. Consequently, receivers face challenges related to acoustic interference
      and auditory masking that are not unlike the human cocktail party problem, which
      refers to the problem of perceiving speech in noisy social settings.
      Understanding the sensory solutions to the cocktail party problem has been a goal
      of research on human hearing and speech communication for several decades.
      Despite a general interest in acoustic signaling in groups, animal behaviorists
      have devoted comparatively less attention toward understanding how animals solve
      problems equivalent to the human cocktail party problem. After illustrating how
      humans and nonhuman animals experience and overcome similar perceptual challenges
      in cocktail-party-like social environments, this article reviews previous
      psychophysical and physiological studies of humans and nonhuman animals to
      describe how the cocktail party problem can be solved. This review also outlines
      several basic and applied benefits that could result from studies of the cocktail
      party problem in the context of animal acoustic communication.

PMID- 18729655
TI  - Analyzing acoustic interactions in natural bullfrog (Rana catesbeiana) choruses.
AB  - Analysis of acoustic interactions between animals in active choruses is complex
      because of the large numbers of individuals present, their high calling rates,
      and the considerable numbers of vocalizations that either overlap or show close
      temporal alternation. The authors describe a methodology for recording chorus
      activity in bullfrogs (Rana catesbeiana) using multiple, closely spaced acoustic
      sensors that provide simultaneous estimates of sound direction and sound
      characteristics. This method provides estimates of location of individual
      callers, even under conditions of call overlap. This is a useful technique for
      understanding the complexity of the acoustic scene faced by animals vocalizing in
      groups.

PMID- 18729656
TI  - Interference risk and the function of dynamic shifts in calling in the gray
      treefrog (Hyla versicolor).
AB  - Male gray treefrogs call to attract females under challenging acoustic
      conditions. At higher chorus densities, there is considerable background noise
      and a good chance that a male's calls will often be overlapped by calls of other
      individuals. Call overlap may reduce the probability of mating because females
      prefer calls with internal pulse structure that is not obscured. With increases
      in acoustic stimulation, males lengthen call duration while simultaneously
      reducing call rate such that "pulse effort" changes little. In our study, we
      tested the "interference risk hypothesis." This proposes that males change call
      duration so that, on average, there will be a sufficient number of pulses and
      interpulse intervals clear of acoustic interference per call to attract a female.
      However, female choice experiments employing call alternatives of different
      durations, rates, intensity levels, and degrees of call overlap refuted this
      hypothesis. Our results leave open the possibilities that the dynamic shift in
      the two components of pulse effort are related to the problem of call detection
      in a noisy environment or are responses by males to the perceived threat of
      competition for females.

PMID- 18729657
TI  - Mechanisms and evolution of synchronous chorusing: emergent properties and
      adaptive functions in Neoconocephalus katydids (Orthoptera: Tettigoniidae).
AB  - Synchronous interactions arise in various animal species that rhythmically
      broadcast acoustic, vibratory, and visual signals. These interactions are
      characterized by a coincidence in both rate and phase of the rhythms of
      neighboring signalers. Theory predicts several ways in which synchronized rhythms
      may specifically benefit the interacting signalers. However, synchrony may also
      arise as an emergent property, a default phenomenon that is neither preferred by
      conspecific receivers evaluating the signals nor advantageous to the signalers
      themselves. Here, we examine several well-studied cases of acoustic synchrony in
      Neoconocephalus katydids (Orthoptera: Tettigoniidae), a New World genus wherein
      males broadcast loud advertisement songs. We report that call synchrony found in
      N. spiza and N. nebrascensis results from two rather different mechanisms of
      rhythm adjustment. Moreover, synchrony in the former species appears to represent
      an incidental byproduct of signal competition between evenly matched males,
      whereas in the latter species synchrony functions as a specific adaptation in
      which cooperating males ensure that critical call features can be perceived by
      females. We discuss the separate evolutionary trajectories that may have led to
      similar outcomes, synchronous chorusing by advertising males, in these closely
      related species.

PMID- 18729658
TI  - Acoustic interactions in broods of nestling birds (Tachycineta bicolor).
AB  - Studies of acoustic interactions in animal groups, such as chorusing insects,
      anurans, and birds, have been invaluable in showing how cooperation and
      competition shape signal structure and use. The begging calls of nestling birds
      are ideal for such studies, because they function both as a cooperative signals
      of the brood's needs and as competitive signals for parental allocation within
      the brood. Nonetheless, studies of acoustic interactions among nestlings are
      rare. Here we review our work on acoustic interactions in nestling tree swallows
      (Tachycineta bicolor), especially how calls are used in competition for parental
      feedings. Nestlings attracted parental attention and responded to acoustic
      interference mainly by increasing call output. However, nestlings also gave more
      similar calls when they called together and decreased their call bandwidth when
      exposed to elevated noise. We suggest that these competitive uses of calls might
      intensify the cooperative brood signal, affecting both parental provisioning and
      vocal development. Given their tremendous variation across species, begging calls
      offer promising opportunities for developmental and comparative studies of
      acoustic signaling.

PMID- 18729659
TI  - Whistle rates of wild bottlenose dolphins (Tursiops truncatus): influences of
      group size and behavior.
AB  - In large social groups acoustic communication signals are prone to signal masking
      by conspecific sounds. Bottlenose dolphins (Tursiops truncatus) use highly
      distinctive signature whistles that counter masking effects. However, they can be
      found in very large groups where masking by conspecific sounds may become
      unavoidable. In this study we used passive acoustic localization to investigate
      how whistle rates of wild bottlenose dolphins change in relation to group size
      and behavioral context. We found that individual whistle rates decreased when
      group sizes got larger. Dolphins displayed higher whistle rates in contexts when
      group members were more dispersed as in socializing and in nonpolarized movement
      than during coordinated surface travel. Using acoustic localization showed that
      many whistles were produced by groups nearby and not by our focal group. Thus,
      previous studies based on single hydrophone recordings may have been
      overestimating whistle rates. Our results show that although bottlenose dolphins
      whistle more in social situations they also decrease vocal output in large groups
      where the potential for signal masking by other dolphin whistles increases.

PMID- 18729660
TI  - Group size and social interactions are associated with calling behavior in
      Carolina chickadees (Poecile carolinensis).
AB  - The complexity of a social group may influence the vocal behavior of group
      members. Recent evidence in Carolina chickadees, Poecile carolinensis, indicated
      that one component of social complexity, group size, influenced the complexity of
      the "chick-a-dee" call, a vocalization functioning in social cohesion.
      Individuals in larger social groups used calls with greater information than did
      individuals in smaller social groups. Here, the authors review this earlier work,
      and describe a recent study indicating that social interactions between females
      and males within female-male pairs of chickadees were associated with rates of
      chick-a-dee call production in the males. Together, these studies suggest that
      the nature and complexity of social interactions among members of chickadee
      social groups influence chick-a-dee calling behavior.

PMID- 18729661
TI  - Convergence of calls as animals form social bonds, active compensation for noisy
      communication channels, and the evolution of vocal learning in mammals.
AB  - The classic evidence for vocal production learning involves imitation of novel,
      often anthropogenic sounds. Among mammals, this has been reported for dolphins,
      elephants, harbor seals, and humans. A broader taxonomic distribution has been
      reported for vocal convergence, where the acoustic properties of calls from
      different individuals converge when they are housed together in captivity or form
      social bonds in the wild. Vocal convergence has been demonstrated for animals as
      diverse as songbirds, parakeets, hummingbirds, bats, elephants, cetaceans, and
      primates. For most species, call convergence is thought to reflect a group
      distinctive identifier, with shared calls reflecting and strengthening social
      bonds. A ubiquitous function for vocal production learning that is starting to
      receive attention involves modifying signals to improve communication in a noisy
      channel. Pooling data on vocal imitation, vocal convergence, and compensation for
      noise suggests a wider taxonomic distribution of vocal production learning among
      mammals than has been generally appreciated. The wide taxonomic distribution of
      this evidence for vocal production learning suggests that perhaps more of the
      neural underpinnings for vocal production learning are in place in mammals than
      is usually recognized.

PMID- 18729662
TI  - Updating von Uexkull: new directions in communication research.
AB  - The study of communication in all its forms has come a long way conceptually and
      methodologically in the last decade, and this is more true of auditory
      communication than of the other sensory modalities. In considering the issues
      involved in communication, it is clear that simple dyadic considerations leave
      out too many important issues. Background noise, eavesdropping, and deception
      represent important neglected factors driving the evolution of the mechanisms,
      development, and ecological adaptiveness of communicatory processes in natural
      environments.

PMID- 18729663
TI  - Challenges and opportunities in public health perspectives on family
      interventions: introduction to the special section.
AB  - This introduction to the special section frames the idea of a public health
      approach to couple and family interventions as focusing upon the impact of
      interventions on outcomes at the population level. It notes the importance of
      looking at how evidence-based interventions can be used more effectively at the
      population level. It also stresses that the goals for population-level studies
      are different from randomized clinical trials. Public health interventions need
      evidence that the interventions can be used in widespread practice, that the
      interventions are cost effective when used as designed, and that monitoring and
      evaluation tools are available for adopting agencies. Finally, this introduction
      introduces the three articles of the series.

PMID- 18729664
TI  - Strengthening couples' relationships with education: social policy and public
      health perspectives.
AB  - There is some evidence that skill-based couples relationship education (CRE)
      enhances couples' maintenance of healthy, committed relationships. This article
      analyzes issues in the balancing of a limited but growing knowledge base on the
      effects of CRE with current social policy that is creating an impetus for
      widespread dissemination of CRE. It is suggested that enough is known to act now,
      and that by doing so, the field has a unique opportunity to substantially (and
      rapidly) add to the existing knowledge base. Specifically, there can be expansion
      of knowledge of the efficacy of CRE with diverse populations and service delivery
      contexts, as well as the influences on the reach of CRE to populations at high
      risk of future relationship difficulties. While the current article focuses on
      CRE, the issues discussed have relevance to warrant dissemination to many areas
      of family psychology intervention.

PMID- 18729665
TI  - Triple P-Positive Parenting Program as a public health approach to strengthening
      parenting.
AB  - Parenting programs have considerable potential to improve the mental health and
      well-being of children, improve family relationships, and benefit the community
      at large. However, traditional clinical models of service delivery reach
      relatively few parents. A public health approach is needed to ensure that more
      parents benefit and that a societal-level impact is achieved. The Triple P
      Positive Parenting Program is a comprehensive, multilevel system of parenting
      intervention that combines within a single intervention universal and more
      targeted interventions for high-risk children and their parents. With Triple P,
      the overarching goal is to enhance the knowledge, skills, and confidence of
      parents at a whole-of-population level and, in turn, to reduce the prevalence
      rates of behavioral and emotional problems in children and adolescents. The
      distinguishing features of the intervention and variables that influence its
      effective implementation are discussed. Self-regulation is a unifying concept
      that is applied throughout the entire system (e.g., to interactions between
      children, parents, service providers, and agencies involved in delivering the
      intervention). Challenges and future directions for the development of public
      health approaches to parenting are discussed.

PMID- 18729666
TI  - Public health approaches to family maltreatment prevention: resetting family
      psychology's sights from the home to the community.
AB  - The authors review recent trends within the family maltreatment research field
      toward a public health approach, discuss the rationale for community-level
      interventions for family maltreatment, and sketch the history and development of
      community-level prevention approaches. Next, to illustrate the both the logistic
      and the scientific challenges of such work, the authors discuss the development
      and testing of an empirically guided, research-community partnership for the
      prevention of family maltreatment, the United States Air Force's NORTH STAR
      initiative (New Orientation to Reduce Threats to Health From Secretive Problems
      That Affect Readiness). Finally, recommendations are made for effective and
      disseminable family maltreatment prevention interventions.

PMID- 18729667
TI  - Bridging the divide: openness in adoption and postadoption psychosocial
      adjustment among birth and adoptive parents.
AB  - Using 323 matched parties of birth mothers and adoptive parents, this study
      examined the association between the degree of adoption openness (e.g., contact
      and knowledge between parties) and birth and adoptive parents' postadoption
      adjustment shortly after the adoption placement (6 to 9 months). Data from birth
      fathers (N = 112), an understudied sample, were also explored. Openness was
      assessed by multiple informants. Results indicated that openness was
      significantly related to satisfaction with adoption process among adoptive
      parents and birth mothers. Increased openness was positively associated with
      birth mothers' postplacement adjustment, as indexed by birth mothers' self
      reports and the interviewers' impression of birth mothers' adjustment. Birth
      fathers' report of openness was associated with their greater satisfaction with
      the adoption process and better postadoption adjustment.

PMID- 18729668
TI  - Behavioral and emotional problems among Italian international adoptees and non
      adopted children: father's and mother's reports.
AB  - This study intends to fill the gap in empirical research carried out in Italy
      regarding international adoptees' behavioral and emotional problems. Assuming a
      multi-informant approach, it aims to compare parents' reports of behavioral
      problems of adopted and non-adopted children and to examine parental agreement.
      The sample was composed of 186 adoptive couples and 195 biological couples with
      the target child between ages 7 and 11 years. The mother and father filled in the
      Child Behavior Checklist (CBCL) separately. Analysis of the CBCL revealed that
      adopted children are perceived by their parents as having more Total and
      Externalizing Problems than are their non-adopted counterparts. Moreover, they
      are more likely to demonstrate attention difficulties and aggressive behavior.
      The agreement between parents turned out to be moderate for adoptive parents and
      slightly lower for the biological ones. Consistent with most adoption research,
      the results confirm the higher risk of behavioral problems among adopted
      children. They also shed light on the significant perceptual discrepancy between
      mothers and fathers, underlining the importance of considering both parents'
      reports in the study of adopted children's adjustment.

PMID- 18729669
TI  - The transportability of multisystemic therapy to Sweden: short-term results from
      a randomized trial of conduct-disordered youths.
AB  - This randomized clinical trial assessed the effectiveness of multisystemic
      therapy (MST) for 156 youths who met the diagnostic criteria for conduct
      disorder. Sweden's 3 largest cities and 1 small town served as the recruiting
      area for the study. A mixed factorial design was used, with random allocation
      between MST and treatment as usual groups. Assessments were conducted at intake
      and 7 months after referral. With an intention-to-treat approach, results from
      multiagent and multimethod assessment batteries showed a general decrease in
      psychiatric problems and antisocial behaviors among participants across
      treatments. There were no significant differences in treatment effects between
      the 2 groups. The lack of treatment effect did not appear to be caused by site
      differences or variations in program maturity. MST treatment fidelity was lower
      than that of other studies, although not clearly related to treatment outcomes in
      this study. The results are discussed in terms of differences between Sweden and
      the United States. One difference is the way in which young offenders are
      processed (a child welfare approach vs. a juvenile justice system approach).
      Sociodemographic differences (e.g., rates of poverty, crime, and substance abuse)
      between the 2 countries may also have moderating effects on the rates of
      rehabilitation among young offenders. (PsycINFO Database Record (c) 2008 APA, all
      rights reserved).

PMID- 18729670
TI  - Interdependence of parenting of mothers and fathers of infants.
AB  - This study examined the relations among parenting behaviors of 97 coresident
      mothers and fathers of infants during a dyadic free-play setting. The authors
      examined the extent to which observed sensitive and intrusive parenting behaviors
      in mother-child and father-child dyads were related and how perceived marital
      quality may be associated with the similarity between maternal and paternal
      parenting behaviors. The authors found support for interdependence of parenting
      by mothers and fathers. High perceived marital quality was associated with
      interdependence of sensitive parenting behaviors in mother-infant and father
      infant interactions. Negative parenting behaviors by mothers and fathers were
      interrelated regardless of marital quality. The findings highlight the importance
      of studying parenting by mothers and fathers as embedded within particular family
      systems.

PMID- 18729671
TI  - Reducing depression among at-risk early adolescents: three-year effects of a
      family-centered intervention embedded within schools.
AB  - The Adolescent Transitions Program (ATP) is a family-focused multilevel
      prevention program designed for delivery within public middle schools to target
      parenting factors related to the development of behavior problems in early
      adolescence. The current study examines the effects of the ATP on the development
      of youth depressive symptoms across early adolescence in a sample of 106 high
      risk youths. Youths were recruited in 6th grade, and selected as high risk based
      on teacher and parent reports of behavioral or emotional problems. Depression
      symptoms were based on youth and mother reports in 7th, 8th, and 9th grades.
      Receipt of the family-centered intervention inhibited growth in depressive
      symptoms in high-risk youths over the 3 yearly assessments compared with symptoms
      in high-risk youths in the control group. Results support the notion that
      parental engagement in a program designed to improve parent management practices
      and parent-adolescent relationships can result in collateral benefits to the
      youths' depressive symptoms at a critical transition period of social and
      emotional development.

PMID- 18729672
TI  - Psychological symptoms and marital satisfaction in spouses of Operation Iraqi
      Freedom veterans: relationships with spouses' perceptions of veterans'
      experiences and symptoms.
AB  - Much research has shown that spouses of combat veterans with posttraumatic stress
      disorder (PTSD) have higher rates of psychological and marital distress than do
      spouses of veterans without PTSD; however, very few studies have examined
      potential mechanisms of this increased vulnerability. The current study examined
      spouses of National Guard soldiers recently returned from deployments in Iraq. In
      addition to documenting elevated levels of psychological symptoms in these
      spouses, the authors found that spouses experienced greater symptom severity when
      they perceived high levels of symptoms in soldiers but the soldiers endorsed low
      levels of symptoms. Furthermore, spouses' marital satisfaction was negatively
      linked to soldiers' self-reported symptom severity only when spouses perceived
      that soldiers had experienced low levels of combat activity while deployed. When
      spouses perceived high levels of such activity, soldiers' self-reported symptoms
      had no relationship with spouses' marital satisfaction. These findings highlight
      the importance of interpersonal perceptions in intimate relationships and are
      consistent with the notion that uncontrollable attributions for a relative's
      mental health problems may provide a buffer against relationship distress.
      (PsycINFO Database Record (c) 2008 APA, all rights reserved).

PMID- 18729673
TI  - The coregulation of daily affect in marital relationships.
AB  - This study examined whether changes in individuals' affective states are
      associated with their partners' affect when spouses come together in daily life
      after having spent time apart while pursuing individual activities, as well as
      whether such associations are moderated by individual differences in
      interpersonal insecurity and perspective taking. For 7 consecutive days, spouses
      from 166 married couples reported their affect 6 times per day on 2 dimensions,
      hard affect (angry-calm) and soft affect (sad/depressed-upbeat/content). Within
      couple analyses indicated that spouses' changes in hard affect covaried,
      particularly when they scored high on interpersonal insecurity. Moreover,
      husbands' changes in soft affect covaried with their wives' soft affect when the
      husbands scored high on perspective taking. The results emphasize the
      interconnectedness of spouses' feelings when they reunite, and they identify key
      individual difference variables that strengthen interpersonal transmission of
      emotion in close relationships.

PMID- 18729674
TI  - Retrospective reports of parental physical affection and parenting style: a study
      of Finnish twins.
AB  - Individual differences in parenting behaviors are due, in part, to genetic
      factors. In the present study, the authors sought to determine whether the degree
      of genetic influence varied according to the type of parental behavior under
      consideration. A population-based sample of 2,334 pairs of Finnish twins provided
      ratings on the physical affection, control, abusiveness, and indifference shown
      by their father and mother during childhood. Genetic influences, shared
      environmental influences, and nonshared environmental influences accounted for a
      small-to-medium proportion (17%-30%), a small-to-large proportion (22%-44%), and
      a medium-to-large proportion (37%-55%) of the variance in each parenting measure,
      respectively. There were no significant differences in effect sizes for mothers
      and fathers or across the 4 types of parental behavior. The genetic results may
      reflect characteristic styles with which parents respond to genetically
      influenced behaviors of individuals (gene-environment correlations) or individual
      perceptions of this relationship (gene-person correlation processes). The
      findings have implications for intervention and prevention work with families and
      for interpretation of evidence for interactions between genes and parenting
      behaviors.

PMID- 18729675
TI  - Intimate partner violence and children's reaction to peer provocation: the
      moderating role of emotion coaching.
AB  - The current study examined the relation between intimate partner violence (IPV)
      and children's reactions to a stressful peer interaction in a community-based
      sample. The moderating role of parental emotion coaching in buffering children
      from negative reactions to a peer was also examined. Children participated in a
      peer provocation paradigm and mothers completed the Parent Meta-Emotion
      Interview. Both adaptive (i.e., laughing, ignoring) and maladaptive (i.e.,
      hostile/challenging, odd behaviors) reactions to the provocative peer were
      examined. IPV was positively related to children's laughing and odd behaviors but
      was unrelated to ignoring and hostile/challenging behaviors. Additionally,
      emotion coaching was found to moderate relations between IPV and children's
      laughing and odd behaviors. The importance of understanding protective factors in
      families experiencing IPV and of developing emotion coaching parenting programs
      is discussed.

PMID- 18729676
TI  - Influence of family of origin and adult romantic partners on romantic attachment
      security.
AB  - According to attachment theory, attachment style derives from social experiences
      throughout the life span. The authors tested this expectation by examining
      associations between the quality of observed interaction patterns in the family
      of origin during adolescence and self-reported romantic attachment style and
      observed romantic relationship behaviors in adulthood (ages 25 and 27). Family
      and romantic relationship interactions were rated by trained observers from video
      recordings of structured conversation tasks. Attachment style was assessed with
      items from D. W. Griffin and K. Bartholomew's (1994a) Relationship Scales
      Questionnaire. Observational ratings of warmth and sensitivity in family
      interactions were positively related to similar behaviors by romantic partners
      and to attachment security. In addition, romantic interactions characterized by
      high warmth and low hostility at age 25 predicted greater attachment security at
      27, after controlling for attachment security at age 25. However, attachment
      security at age 25 did not predict later romantic relationship interactions after
      controlling for earlier interactions. These findings underscore the importance of
      close relationships in the development of romantic attachment security but do not
      indicate that attachment security predicts the quality of interactions in
      romantic relationships.

PMID- 18729677
TI  - Marital conflict and support seeking by parents in adolescence: empirical support
      for the parentification construct.
AB  - Parentification, a parent-child dynamic wherein children come to provide ongoing
      emotional support for their parents, has been documented extensively in the
      clinical literature; however, it rarely has been studied systematically. Using a
      community sample of 83 couples and their adolescent children (mean age = 15.26
      years; 52% male, 48% female), the authors linked adolescent self-report of
      parentification to specific youth and adult behaviors using multiple methods and
      examined its associations with youth adjustment problems. The parentification
      measure demonstrated strong internal consistency and 1-year stability.
      Parentification was associated with marital conflict, youth perceptions of
      threat, low warmth in the parent-child relationship, and the tendency for youths
      to intervene in marital conflict. Links were also found with youth reports of
      internalizing and externalizing behavior and poorer competency in close
      friendships. These findings thus support the parentification construct and
      provide evidence that parentification may contribute to poor youth outcomes by
      burdening children with developmentally inappropriate responsibilities.

PMID- 18729678
TI  - Low-income, nonresident father involvement with their toddlers: variation by
      fathers' race and ethnicity.
AB  - Using data from a racially and ethnically diverse sample of low-income mothers of
      2-year-old children participating in the Early Head Start Research and Evaluation
      Project (N = 883), the authors examined fathers' education and employment, mother
      father relationship, and mothers' relationships with kin in the household to
      explain variation in nonresident father involvement across racial and ethnic
      groups. Nonresident White fathers were less involved with their children than
      were African American and Latino fathers. This difference was explained by the
      status of mother-father relationships. White nonresident fathers were less likely
      than minority nonresident fathers to maintain romantic relationships with their
      child's mother. Mothers in the White father group were also more likely to re
      partner, which negatively related to biological fathers' involvement. These
      findings suggest that approaches to strengthen nonresident father involvement in
      children's lives need to consider how father ethnicity and mother-father
      relations are associated with differential patterns of father involvement.

PMID- 18729679
TI  - Power assertive discipline, maternal emotional involvement, and child adjustment.
AB  - Despite long-standing research, the relations between power assertive discipline
      and child adjustment continue to be debated. Disentangling disciplinary practices
      from the parent-child emotional climate may aid understanding of how such
      parenting practices impact child adjustment. This study explored longitudinal
      relations between maternal emotional involvement, power assertive discipline, and
      child adjustment in a sample of 35 mothers of infant, toddler, and preschool-age
      children. Results indicate that power assertive discipline may differentially
      impact child adjustment, depending on levels of maternal emotional involvement.

PMID- 18729680
TI  - Parental autonomy support and ethnic culture identification among second
      generation immigrants.
AB  - Born and raised in the United States, children of immigrants often face conflict
      over whether to endorse the norms and traditions of the family's country of
      origin (the natal culture) or those of mainstream U.S. society (the host
      culture). The authors hypothesized that when immigrant parents allow children to
      make their own choices concerning their cultural identity, their children will be
      more likely to internalize the natal culture and will experience greater well
      being. Ninety-nine college-aged 2nd-generation immigrants rated their well-being,
      perceptions of their mother's and father's autonomy support, and their
      endorsement of both natal and U.S. cultures. Results demonstrated that paternal,
      but not maternal, autonomy support predicted greater well-being and greater
      endorsement of the natal culture and that immersion in the natal culture
      predicted some indices of well-being. Several explanations for the possibly
      greater significance of paternal versus maternal autonomy support in the context
      of immigrant families are considered.

PMID- 18729681
TI  - Cocaine abusers with and without alcohol dependence respond equally well to
      contingency management treatments.
AB  - Contingency management (CM) treatments are efficacious in treating cocaine abuse.
      Despite high prevalence rates of alcohol dependence (AD) among individuals with
      cocaine use disorders, relatively little data are available regarding whether
      comorbid AD is associated with poorer treatment outcomes in general, or in
      response to CM in particular. Using data from 3 randomized trials of CM for
      cocaine abuse, we compared cocaine abusers (N = 393) with and without AD in terms
      of abstinence and psychosocial problems during treatment and follow-up. Alcohol
      dependent participants had more lifetime years of cocaine and alcohol use and
      greater severity of alcohol and psychiatric problems. CM was positively and
      significantly associated with longer durations of abstinence, regardless of AD
      status. Although not significantly associated with abstinence, the presence of AD
      was related to improvement in medical and alcohol-related problems during
      treatment, and these gains were maintained posttreatment. The results suggest
      that cocaine abusers benefit equally well from CM treatments, regardless of AD
      status. Further, alcohol dependent participants are able to offset greater
      baseline severity in psychosocial functioning and maintain these improvements
      with CM.

PMID- 18729682
TI  - Limitations to the generality of cocaine locomotor sensitization.
AB  - Repeated exposure to cocaine often leads to tolerance to effects on operant
      behavior, whereas sensitization often develops to effects on locomotor activity.
      The purpose of the present set of experiments was to examine if locomotor
      sensitization to cocaine would develop in the presence or absence of an operant
      contingency in rats. In Experiment 1, rats lever pressed on an FR schedule of
      reinforcement, and were administered chronic cocaine. Tolerance to effects of
      cocaine on lever pressing developed in most subjects. No subjects developed
      locomotor sensitization even when the operant contingency was removed. Experiment
      2 examined effects of chronic cocaine administration in rats with no exposure to
      an operant contingency. Tolerance developed to locomotor effects of cocaine in
      some subjects, but none developed sensitization. In Experiment 3, rats were
      exposed to a shorter drug regimen, and given time off before a sensitization-test
      session. Some, but not all subjects showed locomotor sensitization during the
      test session. The present results, therefore, show that locomotor sensitization
      to cocaine is not an inevitable consequence of repeated exposure to the drug.

PMID- 18729683
TI  - Effects of nicotine and depressive traits on affective priming of lateralized
      emotional word identification.
AB  - Based on evidence suggesting that depressive traits, emotional information
      processing, and the effects of nicotine may be mediated by lateralized brain
      mechanisms, analyses assessed the influence of depressive traits and nicotine
      patch on emotional priming of lateralized emotional word identification in 61
      habitual smokers. Consistent with hypotheses, nicotine as compared to placebo
      patch enhanced right visual field (RVF) emotional word identification while
      decreasing performance of emotional word identification in the left visual field
      (LVF). Nicotine also enhanced positive affect and decreased negative affect.
      Consistent with the Heller model of depression, scoring high in depressive traits
      was associated with a general decrease in LVF emotional word identification.
      Additionally, this general LVF deficit was especially pronounced for positive
      word identification in individuals scoring high in trait depression. Positive
      primes facilitated positive target identification in the RVF and negative primes
      facilitated negative target identification in the LVF. Thus, nicotine promoted a
      LVF word-identification deficit similar to that observed in those with depressive
      traits. However, nicotine also enhanced RVF processing and reduced negative
      affect, whereas it enhanced positive affect.

PMID- 18729684
TI  - Subliminal processing of smoking-related and affective stimuli in tobacco
      addiction.
AB  - Cognitive processing biases toward smoking-related and affective cues may play a
      role in tobacco dependence. Because processing biases may occur outside conscious
      awareness, the current study examined processing of smoking-related and affective
      stimuli presented at subliminal conditions. A pictorial subliminal repetition
      priming task was administered to three groups: (1) Nonsmokers (n = 56); (2)
      Smokers (> or =10 cigarettes/day) who had been deprived from smoking for 12 h (n
      = 47); and (3) Nondeprived smokers (n = 66). Prime stimuli were presented briefly
      (17 ms) and were followed by a mask (to render them unavailable to conscious
      awareness) and then a target. Participants were required to make a speeded
      classification to the target. A posttask awareness check was administered to
      ensure that participants could not consciously perceive the briefly presented
      primes (i.e., smoking paraphernalia, neutral office supplies, and happy, angry,
      and neutral facial expressions). The groups differed in the degree to which they
      exhibited a processing bias for smoking-related stimuli, F(2, 166) = 4.99, p =
      .008. Deprived smokers exhibited a bias toward processing smoking (vs. neutral
      office supply) stimuli, F(1, 46) = 5.67, p = .02, whereas nondeprived smokers and
      nonsmokers did not (ps > .22). The three groups did not differ in the degree to
      which they exhibited a subliminal processing bias for affective stimuli. Tobacco
      deprivation appears to increase smokers' subliminal processing of smoking-related
      (vs. neutral) stimuli but does not influence subliminal processing of affective
      stimuli. Future research should investigate whether subliminal biases toward
      smoking-related stimuli influence relapse.

PMID- 18729687
TI  - Effects of a context shift and multiple context extinction on reactivity to
      alcohol cues.
AB  - Cue exposure treatment (CET) attempts to reduce the influence of conditioned
      substance cues on addictive behavior via extinction, but has received only modest
      empirical support in clinical trials. This may be because extinction learning
      appears to be context dependent and a change in context may result in a return of
      conditioned responding (i.e., renewal), although this has received only limited
      empirical examination. The current study used a 4-session laboratory analogue of
      CET to examine whether a change in context following 3 sessions of alcohol cue
      exposure with response prevention would result in renewal of conditioned
      responding. In addition, this study examined whether conducting extinction in
      multiple contexts would attenuate renewal of conditioned responding. In one-way
      between-subjects design, 73 heavy drinkers (71% men) were randomized to 3
      conditions: (a) single context extinction (extinction to alcohol cues in the same
      context for 3 sessions followed by a context shift at the fourth session), (b)
      multiple context extinction (extinction to alcohol cues in different contexts
      each day for all 4 sessions), and (c) pseudoextinction control condition
      (exposure to neutral cues in the same context for 3 sessions followed by exposure
      to alcohol cues at the fourth session). The results revealed the predicted cue
      reactivity and extinction effects, but the hypotheses that a context shift would
      generate renewed cue reactivity and that multiple contexts would enhance
      extinction were not supported. Methodological aspects of the study and the need
      for parametric data on the context dependency of extinction to alcohol cues are
      discussed.

PMID- 18729685
TI  - Panic reactivity to voluntary hyperventilation challenge predicts distress
      tolerance to bodily sensations among daily cigarette smokers.
AB  - The present investigation examined the extent to which panic reactivity to bodily
      sensations is related to distress tolerance (DT) among daily smokers. It was
      hypothesized that panic reactivity to an initial voluntary hyperventilation
      (i.e., whether participants met criteria for a DSM-IV panic attack; PA) would
      predict the relative degree of task persistence on a second hyperventilation
      trial (DT) above and beyond the variance accounted for by anxiety sensitivity
      (AS), negative affectivity (NA), cigarette smoking rate, and self-reported
      discomfort intolerance (DI). Participants were 95 daily smokers (58% women; M
      sub(age) = 29.0, SD = 12.2) who completed a battery of questionnaires and two
      voluntary hyperventilation procedures. Results indicated PA status significantly
      predicted DT, above and beyond the theoretically relevant covariates of AS, NA,
      cigarettes per day, and DI ( p < .05). Such a result is consistent with
      theoretical models and empirical findings on emotional reactivity that suggest
      panic responsivity to internal cues may represent a key explanatory construct in
      terms of level of DT to interoceptive stimuli.

PMID- 18729688
TI  - Behavioral economic analysis of natural resolution of drinking problems using IVR
      self-monitoring.
AB  - This study investigated whether a behavioral economic index of the value of
      rewards available over different time horizons predicted patterns of alcohol
      consumption shortly after natural resolution when the risk of relapse is high.
      Using a computerized interactive voice response (IVR) telephone system, untreated
      problem drinkers (n = 41) self-monitored their daily drinking, monetary
      expenditures, and surrounding contexts over intervals that ranged from a maximum
      of 42 to 128 days. Expanded Timeline Followback interviews were conducted before
      and after the IVR interval and 1 year after the baseline assessment. Stable
      resolutions generally and moderation resolutions specifically were associated
      with proportionally more preresolution expenditures on savings and less on
      alcohol compared to heavy drinking outcomes. The findings replicated and extended
      earlier research and suggested that the extent to which problem drinkers
      organized their behavior over longer intervals, even when drinking abusively,
      helped identify who resolved, including who transitioned to stable moderation.

PMID- 18729690
TI  - The mere perception of elaboration creates attitude certainty: exploring the
      thoughtfulness heuristic.
AB  - Attitude theory has long proposed a mechanism through which antecedents of
      message elaboration produce attitude strength consequences. However, little
      direct evidence exists for the intervening process. The proposed thoughtfulness
      heuristic holds that perceiving that more thought has taken place leads to
      greater attitude certainty. Two roles were established for this heuristic: first
      as a mediator of the impact of antecedents of elaboration on attitude certainty
      and second as a way to influence attitude certainty independent of actual
      elaboration. In Studies 1 and 2, antecedents of elaboration (need for cognition,
      distraction) impacted attitude certainty because they impacted the actual amount
      of processing, which in turn affected perceptions of the amount of processing. In
      Studies 3 and 4, a manipulation of perceived thought impacted certainty
      independent of actual thought (i.e., after thinking had already occurred).
      Furthermore, the thoughtfulness heuristic was shown to influence behavioral
      intentions, establishing perceived amount of processing as both a mediator and an
      independent cause of attitude strength consequences.

PMID- 18729689
TI  - The P300 as an electrophysiological probe of alcohol expectancy.
AB  - Language-based measures indicate that alcohol expectancies influence alcohol
      consumption. To relate these measures to brain actions that precede verbal
      output, the P300 component of the Event-related potentials (ERPs) was used to
      detect violations of individually held alcohol expectancies. As predicted, P300
      amplitude elicited by negative alcohol expectancy stimuli was positively
      correlated with endorsement of positive/arousing alcohol expectancies on the
      language-based measures, such that the higher an individual's positive/arousing
      expectancies, the larger was the P300 elicited by negative alcohol expectancy
      stimuli. These results demonstrated concordance between language-based measures
      of alcohol expectancies and electrophysiological probes of expectancy. While it
      remains unknown whether these expectancy processes are integral to decision
      pathways that influence consumption, these findings suggest that such processing
      can occur very quickly outside of conscious deliberation.

PMID- 18729691
TI  - Increasing and decreasing motor and cognitive output: a model of general action
      and inaction goals.
AB  - General action and inaction goals can influence the amount of motor or cognitive
      output irrespective of the type of behavior in question, with the same stimuli
      producing trivial and important motor and cognitive manifestations normally
      viewed as parts of different systems. A series of experiments examined the
      effects of instilling general action and inaction goals using word primes, such
      as "action" and "rest." The first 5 experiments showed that the same stimuli
      influenced motor output, such as doodling on a piece of paper and eating, as well
      as cognitive output, such as recall and problem solving. The last 2 experiments
      supported the prediction that these diverse effects can result from the
      instigation of general action and inaction goals. Specifically, these last 2
      studies confirmed that participants were motivated to achieve active or inactive
      states and that attaining them decreased the effects of the primes on behavior.

PMID- 18729692
TI  - The role of control motivation in mortality salience effects on ingroup support
      and defense.
AB  - Terror management research has shown that mortality salience (MS) leads to
      increased support and defense of cultural ingroups and their norms (i.e.,
      worldview defense, WD). The authors investigated whether these effects can be
      understood as efforts to restore a generalized sense of control by strengthening
      one's social ingroup. In Studies 1-3, the authors found that WD was only
      increased following pure death salience, compared with both dental pain salience
      and salience of self-determined death. As both the pure death and the self
      determined death conditions increased accessibility of death-related thoughts
      (Study 4), these results do not emerge because only the pure death induction
      makes death salient. At the same time, Study 5 showed that implicitly measured
      control motivation was increased in the pure death salience condition but not
      under salience of both self-determined death and dental pain. Finally, in Study
      6, the authors manipulated MS and control salience (CS) independently and found a
      main effect for CS but not for MS on WD. The results are discussed with regard to
      a group-based control restoration account of terror management findings.

PMID- 18729693
TI  - Moods as spotlights: the influence of mood on accessibility effects.
AB  - Three studies explore the manner in which one's mood may affect the use and
      impact of accessible information on judgments. Specifically, the authors
      demonstrated that positive and negative moods differentially influence the
      direction of accessibility effects (assimilation, contrast) by determining
      whether abstract traits or concrete actor-trait links are primed. Study 1
      investigated the impact of positive versus negative mood on the judgmental impact
      of trait-implying behaviors and found that positive moods lead to assimilation
      and negative moods to contrast. In Study 2, this effect was replicated in a
      subliminal priming paradigm. In Study 3, it was demonstrated that the type of
      information activated by trait-implying behaviors is indeed mood dependent, such
      that abstract trait information is activated in a positive mood, whereas specific
      actor-trait links are activated in a negative mood.

PMID- 18729694
TI  - Creating and undermining social support in communal relationships: the role of
      compassionate and self-image goals.
AB  - In 2 studies, the authors examined whether relationship goals predict change in
      social support and trust over time. In Study 1, a group of 199 college freshmen
      completed pretest and posttest measures of social support and interpersonal trust
      and completed 10 weekly reports of friendship goals and relationship experiences.
      Average compassionate goals predicted closeness, clear and connected feelings,
      and increased social support and trust over the semester; self-image goals
      attenuated these effects. Average self-image goals predicted conflict,
      loneliness, and afraid and confused feelings; compassionate goals attenuated
      these effects. Changes in weekly goals predicted changes in goal-related affect,
      closeness, loneliness, conflict, and beliefs about mutual and individualistic
      caring. In Study 2, a group of 65 roommate pairs completed 21 daily reports of
      their goals for their roommate relationship. Actors' average compassionate and
      self-image goals interacted to predict changes over 3 weeks in partners' reports
      of social support received from and given to actors; support that partners gave
      to actors, in turn, predicted changes in actors' perceived available support,
      indicating that people with compassionate goals create a supportive environment
      for themselves and others, but only if they do not have self-image goals.

PMID- 18729695
TI  - Coordination success and interpersonal perceptions: matching versus mismatching.
AB  - Coordination is an essential part of social functioning. The authors distinguish
      2 types of coordination: matching and mismatching. In matching, coordination is
      successful if parties choose the same action. In mismatching, coordination is
      successful if people choose different actions. In 3 studies, the authors
      investigated the downstream social consequences of tacit coordination for
      interpersonal perceptions. In all studies, participants repeatedly choose between
      2 bets with equivalent expected values, and payoffs increased either when they
      choose the same bet or when they choose different bets. In the 1st 2 studies,
      coordination success increased the perceptions of interpersonal similarity and
      liking when matching was required but not when mismatching was required. The
      authors' interpretation is that matching responses and coordination success had
      countervailing effects in the mismatching task. Also, percentage of matched
      responses did not affect perceptions when coordination was not required
      (Experiment 2). In 4 person teams, a frequently matching partner was viewed more
      favorably (smarter, more similar to self, and more liked) than were other
      teammates, even when mismatching increased payoffs (Experiment 3).

PMID- 18729697
TI  - Who drives divergence? Identity signaling, outgroup dissimilarity, and the
      abandonment of cultural tastes.
AB  - People often diverge from members of other social groups: They select cultural
      tastes (e.g., possessions, attitudes, or behaviors) that distinguish them from
      outsiders and abandon tastes when outsiders adopt them. But while divergence is
      pervasive, most research on the propagation of culture is based on conformity.
      Consequently, it is less useful in explaining why people might abandon tastes
      when others adopt them. The 7 studies described in this article showed that
      people diverge to avoid signaling undesired identities. A field study, for
      example, found that undergraduates stopped wearing a particular wristband when
      members of the "geeky" academically focused dormitory next door started wearing
      them. Consistent with an identity-signaling perspective, the studies further
      showed that people often diverge from dissimilar outgroups to avoid the costs of
      misidentification. Implications for social influence, identity signaling, and the
      popularity and diffusion of culture are discussed.

PMID- 18729698
TI  - Relationship-contingent self-esteem and the ups and downs of romantic
      relationships.
AB  - Relationship-contingent self-esteem (RCSE) emerges from perspectives on
      authenticity, need fulfillment, and relationship functioning and is an unhealthy
      form of self-esteem that depends on one's relationship. Four studies provided
      evidence of convergent, discriminant, incremental, and predictive validity for
      RCSE. Study 1 tested associations between RCSE and several conceptually related
      and unrelated constructs in multiple samples. In Study 2, the authors employed an
      event-contingent diary procedure to examine reports of self-esteem as a function
      of everyday relationship events. The association between event valence and
      changes in self-esteem became stronger with RCSE, and this interaction remained
      controlling for several parallel interactions by other constructs. Study 3
      employed an interval-contingent diary procedure and found support for a mediation
      model in which the moderating role of RCSE largely occurred through momentary
      emotions, which in turn predicted momentary self-esteem. Study 4 sampled couples
      and found that partners who were both higher in RCSE felt more committed but not
      more satisfied or close.

PMID- 18729699
TI  - The attachment system in fledgling relationships: an activating role for
      attachment anxiety.
AB  - Is it sensible to study attachment dynamics between potential romantic partners
      before they share a full-fledged attachment bond? The present data indicate that
      such an approach may reveal novel insights about initial attraction processes.
      Four studies suggest that the state-like experience of attachment anxiety has
      functional implications within fledgling (i.e., desired or undeveloped) romantic
      relationships, well before the formation of an attachment bond. Studies 1 and 3
      reveal that attachment anxiety directed toward a particular romantic interest is
      elevated before (in comparison with after) participants report being in an
      established relationship. Studies 2 and 3 demonstrate that such partner-specific
      attachment anxiety predicts attachment-relevant outcomes in fledgling
      relationships, including proximity seeking, safe haven, secure base, passionate
      love, and other approach behaviors. These associations were reliable above and
      beyond (and were typically as strong as or stronger than) the effect of sexual
      desire. Finally, Study 4 presents evidence that partner-specific attachment
      anxiety may cause several of these attachment-relevant outcomes. Attachment
      anxiety seems to be a normative experience and may signal the activation of the
      attachment system during the earliest stages of romantic relationships.

PMID- 18729700
TI  - Mental set and creative thought in social conflict: threat rigidity versus
      motivated focus.
AB  - According to the traditional threat-rigidity reasoning, people in social conflict
      will be less flexible, less creative, more narrow-minded, and more rigid in their
      thinking when they adopt a conflict rather than a cooperation mental set. The
      authors propose and test an alternative, motivated focus account that better fits
      existing evidence. The authors report experimental results inconsistent with a
      threat-rigidity account, but supporting the idea that people focus their
      cognitive resources on conflict-related material more when in a conflict rather
      than a cooperation mental set: Disputants with a conflict (cooperation) set have
      broader (smaller) and more (less) inclusive cognitive categories when the domain
      of thought is (un)related to conflict (Experiment 1a-1b). Furthermore, they
      generate more, and more original competition tactics (Experiments 2-4),
      especially when they have low rather than high need for cognitive closure.
      Implications for conflict theory, for motivated information processing, and
      creativity research are discussed.

PMID- 18729701
TI  - Innovation credit: when can leaders oppose their group's norms?
AB  - Two preliminary studies and 5 experiments examined judgments of leaders who
      challenge their group's norms. Participants viewed information about group
      members whose attitudes were normative or deviated in a pronormative or
      antinormative direction. The antinorm member was identified as (a) either a
      nonleader or an established leader (Study 1), (b) an ex-leader (Studies 2 and 5),
      or (c) a future leader (Studies 3, 4, and 5). Antinorm future leaders were judged
      more positively and were granted greater innovation credit (license to innovate
      and remuneration) relative to antinorm members, ex-leaders, and established
      leaders. Results are discussed in terms of the idea that leadership can accrue
      from prototypicality and can also confer the right to define prescriptive norms.
      However, innovation credit is only granted in the case of future leaders.

PMID- 18729702
TI  - Self-expansion and flow in couples' momentary experiences: an experience sampling
      study.
AB  - The self-expansion model of close relationships posits that when couples engage
      in exciting and activating conjoint activities, they feel connected with their
      partners and more satisfied with their relationships. In the present study, the
      experience sampling method was used to examine the predictions of the self
      expansion model in couples' momentary experiences. In addition, the author
      generated several new hypotheses by integrating the self-expansion model with
      existing research on flow. Over the course of 1 week, 20 couples were signaled at
      quasi-random intervals to provide data on 1,265 unique experiences. The results
      suggest that the level of activation experienced during an activity was
      positively related to experience-level relationship quality. This relationship
      was consistent across free-time and nonfree-time contexts and was mediated by
      positive affect. Activation was not found to predict later affect unless the
      level of activation exceeded what was typical for the individual. Also examined
      was the influence of interpersonal context and activity type on self-expansion.
      The results support the self-expansion model and suggest that it could be
      considered under the broader umbrella of flow.

PMID- 18729703
TI  - Low self-esteem prospectively predicts depression in adolescence and young
      adulthood.
AB  - Low self-esteem and depression are strongly correlated in cross-sectional
      studies, yet little is known about their prospective effects on each other. The
      vulnerability model hypothesizes that low self-esteem serves as a risk factor for
      depression, whereas the scar model hypothesizes that low self-esteem is an
      outcome, not a cause, of depression. To test these models, the authors used 2
      large longitudinal data sets, each with 4 repeated assessments between the ages
      of 15 and 21 years and 18 and 21 years, respectively. Cross-lagged regression
      analyses indicated that low self-esteem predicted subsequent levels of
      depression, but depression did not predict subsequent levels of self-esteem.
      These findings held for both men and women and after controlling for content
      overlap between the self-esteem and depression scales. Thus, the results
      supported the vulnerability model, but not the scar model, of self-esteem and
      depression.

PMID- 18729705
TI  - Negotiators who give too much: unmitigated communion, relational anxieties, and
      economic costs in distributive and integrative bargaining.
AB  - A series of studies found that the personality dimension of unmitigated communion
      (H. L. Fritz & V. S. Helgeson, 1998) leads negotiators to make concessions to
      avoid straining relationships. Results indicate that even within the population
      of successful business executives, this dimension of relational anxiety can be
      identified distinctly from more general relational orientations, such as
      agreeableness, and that it distinctly predicts accommodating tendencies in
      everyday conflicts. In economic games, unmitigated communion predicts giving in
      contexts in which the relational norm of reciprocity applies, but not in contexts
      tapping instrumental or altruistic motives for cooperation. In distributive
      negotiations, the effect of unmitigated communion in lowering a negotiator's
      outcome is mediated by prenegotiation anxieties about relational strain and plans
      to make large concessions if needed to avoid impasse (lower reservation points).
      In integrative negotiations, high unmitigated communion on both sides of the
      negotiation dyad results in relational accommodation, evidenced by decreased
      success in maximizing economic joint gain but increased subjective satisfaction
      with the relationship.

PMID- 18729704
TI  - Searching for and finding meaning in collective trauma: results from a national
      longitudinal study of the 9/11 terrorist attacks.
AB  - The ability to make sense of events in one's life has held a central role in
      theories of adaptation to adversity. However, there are few rigorous studies on
      the role of meaning in adjustment, and those that have been conducted have
      focused predominantly on direct personal trauma. The authors examined the
      predictors and long-term consequences of Americans' searching for and finding
      meaning in a widespread cultural upheaval--the terrorist attacks of September 11,
      2001--among a national probability sample of U.S. adults (N=931). Searching for
      meaning at 2 months post-9/11 was predicted by demographics and high acute stress
      response. In contrast, finding meaning was predicted primarily by demographics
      and specific early coping strategies. Whereas searching for meaning predicted
      greater posttraumatic stress (PTS) symptoms across the following 2 years, finding
      meaning predicted lower PTS symptoms, even after controlling for pre-9/11 mental
      health, exposure to 9/11, and acute stress response. Mediation analyses suggest
      that finding meaning supported adjustment by reducing fears of future terrorism.
      Results highlight the role of meaning in adjustment following collective traumas
      that shatter people's fundamental assumptions about security and invulnerability.

PMID- 18729706
TI  - Culture, cross-role consistency, and adjustment: testing trait and cultural
      psychology perspectives.
AB  - Trait and cultural psychology perspectives on cross-role consistency and its
      relation to adjustment were examined in 2 individualistic cultures, the United
      States (N=231) and Australia (N=195), and 4 collectivistic cultures, Mexico
      (N=199), the Philippines (N=195), Malaysia (N=217), and Japan (N=180). Cross-role
      consistency in trait ratings was evident in all cultures, supporting trait
      perspectives. Cultural comparisons of mean consistency provided support for
      cultural psychology perspectives as applied to East Asian cultures (i.e., Japan)
      but not collectivistic cultures more generally. Some but not all of the
      hypothesized predictors of consistency were supported across cultures. Cross-role
      consistency predicted aspects of adjustment in all cultures, but prediction was
      most reliable in the U.S. sample and weakest in the Japanese sample. Alternative
      constructs proposed by cultural psychologists--personality coherence, social
      appraisal, and relationship harmony--predicted adjustment in all cultures but
      were not, as hypothesized, better predictors of adjustment in collectivistic
      cultures than in individualistic cultures.

PMID- 18729707
TI  - A new consequence of Simpson's paradox: stable cooperation in one-shot prisoner's
      dilemma from populations of individualistic learners.
AB  - Theories of choice in economics typically assume that interacting agents act
      individualistically and maximize their own utility. Specifically, game theory
      proposes that rational players should defect in one-shot prisoners' dilemmas
      (PD). Defection also appears to be the inevitable outcome for agents who learn by
      reinforcement of past choices, because whatever the other player does, defection
      leads to greater reinforcement on each trial. In a computer simulation and 4
      experiments, the authors show that, apparently paradoxically, when players'
      choices are correlated by an exogenous factor (here, the cooperativeness of the
      specific PD chosen), people obtain greater average reinforcement for cooperating,
      which can sustain cooperation. This effect arises from a well-known statistical
      paradox, Simpson's paradox. The authors speculate that this effect may be
      relevant to aspects of real-world human cooperative behavior.

PMID- 18729708
TI  - Propagation of innovations in networked groups.
AB  - A novel paradigm was developed to study the behavior of groups of networked
      people searching a problem space. The authors examined how different network
      structures affect the propagation of information in laboratory-created groups.
      Participants made numerical guesses and received scores that were also made
      available to their neighbors in the network. The networks were compared on speed
      of discovery and convergence on the optimal solution. One experiment showed that
      individuals within a group tend to converge on similar solutions even when there
      is an equally valid alternative solution. Two additional studies demonstrated
      that the optimal network structure depends on the problem space being explored,
      with networks that incorporate spatially based cliques having an advantage for
      problems that benefit from broad exploration, and networks with greater long
      range connectivity having an advantage for problems requiring less exploration.
      (PsycINFO Database Record (c) 2008 APA, all rights reserved).

PMID- 18729709
TI  - Perception as evidence accumulation and Bayesian inference: insights from masked
      priming.
AB  - The authors argue that perception is Bayesian inference based on accumulation of
      noisy evidence and that, in masked priming, the perceptual system is tricked into
      treating the prime and the target as a single object. Of the 2 algorithms
      considered for formalizing how the evidence sampled from a prime and target is
      combined, only 1 was shown to be consistent with the existing data from the
      visual word recognition literature. This algorithm was incorporated into the
      Bayesian Reader model (D. Norris, 2006), and its predictions were confirmed in 3
      experiments. The experiments showed that the pattern of masked priming is not a
      fixed function of the relations between the prime and the target but can be
      changed radically by changing the task from lexical decision to a same-different
      judgment. Implications of the Bayesian framework of masked priming for
      unconscious cognition and visual masking are discussed.

PMID- 18729710
TI  - The goal of consistency as a cause of information distortion.
AB  - Why, during a decision between new alternatives, do people bias their evaluations
      of information to support a tentatively preferred option? The authors test the
      following 3 decision process goals as the potential drivers of such distortion of
      information: (a) to reduce the effort of evaluating new information, (b) to
      increase the separation between alternatives, and (c) to achieve consistency
      between old and new units of information. Two methods, the nonconscious priming
      of each goal and assessing the ambient activation levels of multiple goals,
      reveal that the goal of consistency drives information distortion. Results
      suggest the potential value of combining these methods in studying the dynamics
      of multiple, simultaneously active goals.

PMID- 18729711
TI  - Detection of emotional faces: salient physical features guide effective visual
      search.
AB  - In this study, the authors investigated how salient visual features capture
      attention and facilitate detection of emotional facial expressions. In a visual
      search task, a target emotional face (happy, disgusted, fearful, angry, sad, or
      surprised) was presented in an array of neutral faces. Faster detection of happy
      and, to a lesser extent, surprised and disgusted faces was found both under
      upright and inverted display conditions. Inversion slowed down the detection of
      these faces less than that of others (fearful, angry, and sad). Accordingly, the
      detection advantage involves processing of featural rather than configural
      information. The facial features responsible for the detection advantage are
      located in the mouth rather than the eye region. Computationally modeled visual
      saliency predicted both attentional orienting and detection. Saliency was
      greatest for the faces (happy) and regions (mouth) that were fixated earlier and
      detected faster, and there was close correspondence between the onset of the
      modeled saliency peak and the time at which observers initially fixated the
      faces. The authors conclude that visual saliency of specific facial features-
      especially the smiling mouth--is responsible for facilitated initial orienting,
      which thus shortens detection. (PsycINFO Database Record (c) 2008 APA, all rights
      reserved).

PMID- 18729712
TI  - Associative and strategic components of episodic memory: a life-span
      dissociation.
AB  - The authors investigated the strategic component (i.e., elaboration and
      organization of episodic features) and the associative component (i.e., binding
      processes) of episodic memory and their interactions in 4 age groups (10-12, 13
      15, 20-25, and 70-75 years of age). On the basis of behavioral and neural
      evidence, the authors hypothesized that the two components are functionally
      related but follow different life-span gradients. In a fully crossed design, age
      differences in recognition memory for single words versus word pairs (associative
      demand manipulation) were examined under instructions that emphasized item, pair,
      or elaborative-pair encoding (strategy manipulation). As predicted, the results
      showed that the strategic and associative components follow different life-span
      trajectories. Relative to younger adults, children's difficulties in episodic
      memory primarily reflected lower levels of strategic functioning. In contrast,
      older adults showed impairments in both strategic and associative components. The
      authors conclude that the comparison of strategic and associative components of
      episodic memory across the life span helps to delineate the two components'
      unique and interactive contributions to episodic memory performance.

PMID- 18729713
TI  - The special status of actions in causal reasoning in rats.
AB  - A. P. Blaisdell, K. Sawa, K. J. Leising, and M. R. Waldmann (2006) reported
      evidence for causal reasoning in rats. After learning through Pavlovian
      observation that Event A (a light) was a common cause of Events X (an auditory
      stimulus) and F (food), rats predicted F in the test phase when they observed
      Event X as a cue but not when they generated X by a lever press. Whereas
      associative accounts predict associations between X and F regardless of whether X
      is observed or generated by an action, causal-model theory predicts that the
      intervention at test should lead to discounting of A, the regular cause of X. The
      authors report further tests of causal-model theory. One key prediction is that
      full discounting should be observed only when the alternative cause is viewed as
      deterministic and independent of other events, 2 hallmark features of actions but
      not necessarily of arbitrary events. Consequently, the authors observed
      discounting with only interventions but not other observable events (Experiments
      1 and 2). Moreover, rats were capable of flexibly switching between observational
      and interventional predictions (Experiment 3). Finally, discounting occurred on
      the very first test trial (Meta-Analysis). These results confirm causal-model
      theory but refute associative accounts.

PMID- 18729714
TI  - Multiple confidence estimates as indices of eyewitness memory.
AB  - Eyewitness identification decisions are vulnerable to various influences on
      witnesses' decision criteria that contribute to false identifications of innocent
      suspects and failures to choose perpetrators. An alternative procedure using
      confidence estimates to assess the degree of match between novel and previously
      viewed faces was investigated. Classification algorithms were applied to
      participants' confidence data to determine when a confidence value or pattern of
      confidence values indicated a positive response. Experiment 1 compared confidence
      group classification accuracy with a binary decision control group's accuracy on
      a standard old-new face recognition task and found superior accuracy for the
      confidence group for target-absent trials but not for target-present trials.
      Experiment 2 used a face mini-lineup task and found reduced target-present
      accuracy offset by large gains in target-absent accuracy. Using a standard lineup
      paradigm, Experiments 3 and 4 also found improved classification accuracy for
      target-absent lineups and, with a more sophisticated algorithm, for target
      present lineups. This demonstrates the accessibility of evidence for recognition
      memory decisions and points to a more sensitive index of memory quality than is
      afforded by binary decisions.

PMID- 18729715
TI  - The acquisition of robust and flexible cognitive skills.
AB  - The authors introduce a model of skill acquisition that incorporates elements of
      both traditional models and models based on embedded cognition by striking a
      balance between top-down and bottom-up control. A knowledge representation is
      used in which pre- and postconditions are attached to actions. This model
      captures improved performance due to learning not only in terms of shorter
      solution times and lower error rates during the task but also in an increased
      flexibility to solve similar problems and robustness against unexpected events.
      In 3 experiments using a complex aviation task, the authors contrasted
      instructions that explicitly stated pre- and postconditions with conventional
      instructions that did not. The instructions with pre- and postconditions led to
      better and more robust performance than other instructions, especially on
      problems that required transfer. The parameters of the model were estimated to
      obtain a quantitative fit of the results of Experiment 1, which was then
      successfully used to predict the results of Experiments 2 and 3.

PMID- 18729716
TI  - Decomposition of repetition priming components in picture naming.
AB  - Cognitive mechanisms underlying repetition priming in picture naming were
      decomposed in several experiments. Sets of encoding manipulations meant to
      selectively prime or reduce priming in object identification or word production
      components of picture naming were combined factorially to dissociate processes
      underlying priming in picture naming. Experiments 1, 2, and 3 were conducted with
      Spanish-English bilingual participants and bilingual materials. Experiments 4,
      5A, and 5B were single-language experiments in English or Spanish. A simple
      process model was used to formalize the theoretical predictions and test them
      across all experiments simultaneously. Object identification and word production
      processes were selectively influenced in an additive manner, which suggests that
      the 2 sets of processes are independent and sequential. The patterns of
      facilitation support a quantitative model of transfer-appropriate processing in
      which shared processes from encoding to test are the causal basis and speeded
      processes are the mechanism of facilitation.

PMID- 18729718
TI  - Simple dual tasking recruits prefrontal cortices in chronic severe traumatic
      brain injury patients, but not in controls.
AB  - The ability to carry out two tasks simultaneously, dual tasking, is specifically
      impaired after traumatic brain injury (TBI). The aim of the present study was to
      investigate the neuronal correlates to this increased dual cost in chronic severe
      TBI patients (n = 10) compared to healthy controls (n = 11) using functional
      magnetic resonance imaging (fMRI) at 3 Tesla (T). The tasks were a visual search
      and a simple two-fingers button press motor task. Performance data demonstrated
      similar and significant dual task interference in both TBI patients and controls
      using a linear mixed model. However, principal component analysis showed that TBI
      patients and controls could be classified into different categories based on
      motor activity in the single compared to the dual task condition, thus reflecting
      the increased variability in the performance in the TBI group. Random effects
      between-group analysis demonstrated significantly reduced activation in the TBI
      group in both single task conditions in the occipital and posterior cingulate
      cortices, and for the visual task also in the thalami. This pattern was reversed
      in the dual task condition with significantly increased activation of a
      predominantly left lateralized prefrontal-anterior midline-parietal network in
      the TBI group compared to the controls. The increase in activation occurred
      within regions described to be engaged in healthy volunteers as dual task cost
      increases. This finding points to substitution, functional reorganization within
      the primary network subserving the task, following TBI, and demonstrates more
      effortful processing. Recruitment of these additional prefrontal resources may be
      connected to serial rather than parallel processing in low level dual tasking in
      TBI. Thus, in severe TBI, low level dual task performance depends on increased
      attentional and executive guidance.

PMID- 18729719
TI  - Cortical injury increases cholesterol 24S hydroxylase (Cyp46) levels in the rat
      brain.
AB  - In traumatic brain injury (TBI), cellular loss from initial impact as well as
      secondary neurodegeneration leads to increased cholesterol and lipid debris at
      the site of injury. Cholesterol accumulation in the periphery can trigger
      inflammatory mechanisms while cholesterol clearance may be anti-inflammatory.
      Here we investigated whether TBI altered the regulation of cholesterol 24S
      hydroxylase (Cyp46), an enzyme that converts cholesterol to the more hydrophilic
      24S-hydroxycholesterol. We examined by Western blot and immunohistochemistry
      changes in Cyp46 expression following fluid percussion injury. Under normal
      conditions, most Cyp46 was present in neurons, with very little measurable in
      glia. Cyp46 levels were significantly increased at 7 days post-injury, and cell
      type specific analysis at 3 days post-injury showed a significant increase in
      levels of Cyp46 (84%) in microglia. Since 24-hydroxycholesterol induces
      activation of genes through the liver X receptor (LXR), we examined protein
      levels of ATP-binding cassette transporter A1 and apolipoprotein E, two LXR
      regulated cholesterol homeostasis proteins. Apolipoprotein E and ATP-binding
      cassette transporter A1 were increased at 7 days post-injury, indicating that
      increased LXR activity coincided with increased Cyp46 levels. We found that
      activation of primary rat microglia by LPS in vitro caused increased Cyp46
      levels. These data suggest that increased microglial Cyp46 activity is part of a
      system for removal of damaged cell membranes post-injury, by conversion of
      cholesterol to 24-hydroxycholesterol and by activation of LXR-regulated gene
      transcription.

PMID- 18729720
TI  - The phosphorylated axonal form of the neurofilament subunit NF-H (pNF-H) as a
      blood biomarker of traumatic brain injury.
AB  - The detection of neuron-specific proteins in blood might allow quantification of
      the degree of neuropathology in experimental and clinical contexts. We have been
      studying a novel blood biomarker of axonal injury, the heavily phosphorylated
      axonal form of the high molecular weight neurofilament subunit NF-H (pNF-H). We
      hypothesized that this protein would be released from damaged and degenerating
      neurons following experimental traumatic brain injury (TBI) in amounts large
      enough to allow its detection in blood and that the levels detected would reflect
      the degree of injury severity. An enzyme-linked immunosorbent assay (ELISA)
      capture assay capable of detecting nanogram amounts of pNF-H was used to test
      blood of rats subjected to experimental TBI using a controlled cortical impact
      (CCI) device. Animals were subjected to a mild (1.0 mm), moderate (1.5 mm), or
      severe (2.0 mm) cortical contusion, and blood samples were taken at defined times
      post-injury. The assay detected the presence of pNF-H as early as 6 h post
      injury; levels peaked at 24-48 h, and then slowly decreased to baseline over
      several days post-injury. No signal above baseline was detectable in control
      animals. Analysis of variance (ANOVA) showed a significant effect of lesion
      severity, and post hoc analysis revealed that animals given a moderate and severe
      contusion showed higher levels of blood pNF-H than controls. In addition, the
      peak levels of pNF-H detected at both 24 and 48 h post-injury correlated with the
      degree of injury as determined by volumetric analysis of spared cortical tissue.
      Relative amounts of pNF-H were also determined in different areas of the central
      nervous system (CNS) and were found to be highest in regions containing large
      diameter axons, including spinal cord and brainstem, and lowest in the cerebral
      cortex and hippocampus. These findings suggest that the measurement of blood
      levels of pNF-H is a convenient method for assessing neuropathology following
      TBI.

PMID- 18729721
TI  - A test of the "flexible stem" model of evolution: ancestral plasticity, genetic
      accommodation, and morphological divergence in the threespine stickleback
      radiation.
AB  - If an ancestral stem group repeatedly colonizes similar environments,
      developmental plasticity specific to that group should consistently give rise to
      similar phenotypes. Parallel selection on those similar phenotypes could lead to
      the repeated evolution of characteristic ecotypes, a property common to many
      adaptive radiations. A key prediction of this "flexible stem" model of adaptive
      radiation is that patterns of phenotypic divergence in derived groups should
      mirror patterns of developmental plasticity in their common ancestor. The
      threespine stickleback radiation provides an excellent opportunity to test this
      prediction because the marine form is representative of the ancestral stem group,
      which has repeatedly given rise to several characteristic ecotypes. We examined
      plasticity of several aspects of shape and trophic morphology in response to
      diets characteristic of either the derived benthic ecotype or the limnetic
      ecotype. When marine fish were reared on alternative diets, plasticity of head
      and mouth shape paralleled phenotypic divergence between the derived ecotypes,
      supporting the flexible stem model. Benthic and limnetic fish exhibited patterns
      of plasticity similar to those of the marine population; however, some
      differences in population means were present, as well as subtle differences in
      shape plasticity in the benthic population, indicating a role for genetic
      accommodation in this system.

PMID- 18729722
TI  - X chromosome dosage compensation: how mammals keep the balance.
AB  - The development of genetic sex determination and cytologically distinct sex
      chromosomes leads to the potential problem of gene dosage imbalances between
      autosomes and sex chromosomes and also between males and females. To circumvent
      these imbalances, mammals have developed an elaborate system of dosage
      compensation that includes both upregulation and repression of the X chromosome.
      Recent advances have provided insights into the evolutionary history of how both
      the imprinted and random forms of X chromosome inactivation have come about.
      Furthermore, our understanding of the epigenetic switch at the X-inactivation
      center and the molecular aspects of chromosome-wide silencing has greatly
      improved recently. Here, we review various facets of the ever-expanding field of
      mammalian dosage compensation and discuss its evolutionary, developmental, and
      mechanistic components.

PMID- 18729723
TI  - Molecular pathology of head and neck cancer: implications for diagnosis,
      prognosis, and treatment.
AB  - The prototypic head and neck squamous cell carcinoma (HNSCC) arises from the
      mucosal lining of the upper aerodigestive tract, demonstrates squamous
      differentiation microscopically, involves older men with a long history of
      cigarette smoking and alcohol consumption, and is treated by multimodality
      therapy. HNSCC has long been regarded as a uniform disease process requiring a
      methodical and unwavering therapeutic approach. Divergence in epidemiologic
      trends among HNSCCs arising from different anatomic sites has introduced a view
      that, morphologic repetition aside, head and neck cancers form a heterogeneous
      group. This view has been supported at the molecular genetic level. A more
      complete understanding of the molecular genetics of head and neck cancer is
      providing new insights into long-held but poorly comprehended concepts such as
      field cancerization and is introducing various biomarkers with potential
      application for diagnosing, staging, monitoring, and prognosticating HNSCC.

PMID- 18729724
TI  - The case for cultural competency in psychotherapeutic interventions.
AB  - Cultural competency practices have been widely adopted in the mental health field
      because of the disparities in the quality of services delivered to ethnic
      minority groups. In this review, we examine the meaning of cultural competency,
      positions that have been taken in favor of and against it, and the guidelines for
      its practice in the mental health field. Empirical research that tests the
      benefits of cultural competency is discussed.

PMID- 18729725
TI  - Emotion theory and research: highlights, unanswered questions, and emerging
      issues.
AB  - Emotion feeling is a phase of neurobiological activity, the key component of
      emotions and emotion-cognition interactions. Emotion schemas, the most frequently
      occurring emotion experiences, are dynamic emotion-cognition interactions that
      may consist of momentary/situational responding or enduring traits of personality
      that emerge over developmental time. Emotions play a critical role in the
      evolution of consciousness and the operations of all mental processes. Types of
      emotion relate differentially to types or levels of consciousness. Unbridled
      imagination and the ability for sympathetic regulation of empathy may represent
      both potential gains and losses from the evolution and ontogeny of emotion
      processes and consciousness. Unresolved issues include psychology's neglect of
      levels of consciousness that are distinct from access or reflective consciousness
      and use of the term "unconscious mind" as a dumpster for all mental processes
      that are considered unreportable. The relation of memes and the mirror neuron
      system to empathy, sympathy, and cultural influences on the development of
      socioemotional skills are unresolved issues destined to attract future research.

PMID- 18729726
TI  - Regulation of MHC class I assembly and peptide binding.
AB  - Peptide binding to MHC class I molecules is a component of a folding and assembly
      process that occurs in the endoplasmic reticulum (ER) and uses both cellular
      chaperones and dedicated factors. The involvement of glycoprotein quality-control
      chaperones and cellular oxidoreductases in peptide binding has led to models that
      are gradually being refined. Some aspects of the peptide loading process (e.g.,
      the biosynthesis and degradation of MHC class I complexes) conform to models of
      glycoprotein quality control, but other aspects (e.g., the formation of a stable
      disulfide-linked dimer between tapasin and ERp57) deviate from models of
      chaperone and oxidoreductase function. Here we review what is known about the
      intersection of glycoprotein folding, oxidative reactions, and MHC class I
      peptide loading, emphasizing events that occur in the ER and within the MHC class
      I peptide loading complex.

PMID- 18729727
TI  - Behavioral states help translate dispersal movements into spatial distribution
      patterns of floaters.
AB  - Within the field of spatial ecology, it is important to study animal movements in
      order to better understand population dynamics. Dispersal is a nonlinear process
      through which different behavioral mechanisms could affect movement patterns. One
      of the most common approaches to analyzing the trajectories of organisms within
      patches is to use random-walk models to describe movement features. These models
      express individual movements within a specific area in terms of random-walk
      parameters in an effort to relate movement patterns to the distributions of
      organisms in space. However, only using the movement trajectories of individuals
      to predict the spatial spread of animal populations may not fit the complex
      distribution of individuals across heterogeneous environments. When we
      empirically tested the results from a random-walk model (a residence index) used
      to predict the spatial equilibrium distribution of individuals, we found that the
      index severely underestimated the spatial spread of dispersing individuals. We
      believe this is because random-walk models only account for the effects of
      environmental conditions on individual movements, completely overlooking the
      crucial influence of behavior changes over time. In the future, both aspects
      should be accounted for when predicting general rules of (meta)population
      abundance, distribution, and dynamics from patterns of animal movements.

PMID- 18729728
TI  - Achilles' heel of sociality revealed by energetic poverty trap in cursorial
      hunters.
AB  - This study empirically tests two foundation ecological theories: (1) pack hunting
      is a driver for the evolution of sociality; and (2) species have a finite energy
      potential, whereby increased maintenance costs result in decreased reproductive
      effort. Using activity and prey data from 22 packs of African wild dogs (Lycaon
      pictus), we parameterized a model detailing the energetic cost/benefit of
      cooperative hunting. Larger pack size increased foraging time, prey size, and
      capture probability while reducing chase distance, resulting in a rapidly
      increasing net rate of energy intake up to a pack size of five, which peaked at
      10 individuals and then declined. With a streamlined body plan necessary for
      hypercursoriality limiting stomach capacity in smaller packs, it was demonstrated
      that the group hunting benefit will rather accrue to widely foraging predators
      than to "sit-and-wait" ones. Reproductive effort, measured by the number of pups
      born, revealed smaller litters with decreasing pack size, validated finite energy
      theory, and highlighted a "poverty trap" where smaller groups have lower foraging
      gains, smaller litters, and increased vulnerability to extirpation. Consequently,
      these results demonstrated a mechanistic example of pervasive selection for
      maximal body size (Cope's rule), leading to a macroevolutionary ratchet, where
      sociality linked to hypercursoriality is betrayed by an Achilles' heel.

PMID- 18729729
TI  - Food allergy: recent advances in pathophysiology and treatment.
AB  - Food allergies, defined as an adverse immune response to food proteins, affect as
      many as 6% of young children and 3%-4% of adults in westernized countries, and
      their prevalence appears to be rising. In addition to well-recognized acute
      allergic reactions and anaphylaxis triggered by IgE antibody-mediated immune
      responses to food proteins, there is an increasing recognition of cell-mediated
      disorders such as eosinophilic gastroenteropathies and food protein-induced
      enterocolitis syndrome. We are gaining an increasing understanding of the
      pathophysiology of food allergic disorders and are beginning to comprehend how
      these result from a failure to establish or maintain normal oral tolerance. Many
      food allergens have been characterized at a molecular level, and this knowledge,
      combined with an increasing appreciation of the nature of humoral and cellular
      immune responses resulting in allergy or tolerance, is leading to novel
      therapeutic approaches. Currently, management of food allergies consists of
      educating the patient to avoid ingesting the responsible allergen and initiating
      therapy if ingestion occurs. However, numerous strategies for definitive
      treatment are being studied, including sublingual/oral immunotherapy, injection
      of anti-IgE antibodies, cytokine/anticytokine therapies, Chinese herbal
      therapies, and novel immunotherapies utilizing engineered proteins and strategic
      immunomodulators.

PMID- 18729730
TI  - Goals of inpatient treatment for psychiatric disorders.
AB  - The purpose of the psychiatric hospital changed dramatically during the twentieth
      century. Formerly the primary location for psychiatric treatment, the hospital
      now plays a more circumscribed role within a community-based system of care.
      Crisis stabilization, safety, and a focus on rapid discharge are the critical
      components of the acute inpatient stay. Subspecialized units focus on geriatrics,
      children, adolescents, dual diagnosis (substance abuse and mental illness),
      trauma disorders, eating disorders, and forensics. When integrated with the
      general medical system and a comprehensive base of community-delivered day
      treatment, residential services, and outpatient services, psychiatric
      hospitalization is a humane alternative to long-term institutional care.

PMID- 18729731
TI  - The treatment of hyperhomocysteinemia.
AB  - The unique biochemical profile of homocysteine is characterized by chemical
      reactivity supporting a wide range of molecular effects and by a tendency to
      promote oxidant stress-induced cellular toxicity. Numerous epidemiological
      reports have established hyperhomocysteinemia as an independent risk factor for
      cardiovascular disease, cerebrovascular disease, dementia-type disorders, and
      osteoporosis-associated fractures. Although combined folic acid and B-vitamin
      therapy substantially reduces homocysteine levels, results from randomized
      placebo-controlled clinical trials testing the effect of vitamin therapy on
      outcome in these diseases have generally fallen short of expectations. These
      results have led some to abandon homocysteine monitoring in the management of
      patients with cardiovascular or cognitive disorders. These trials, however, have
      generally included patients with only mildly elevated homocysteine levels and
      have not addressed several clinical scenarios in which homocysteine reduction may
      be effective, including the primary prevention of atherothrombotic disease in
      individuals at low or intermediate risk, or those with severe
      hyperhomocysteinemia.

PMID- 18729733
TI  - Base J: discovery, biosynthesis, and possible functions.
AB  - In 1993, a new base, beta-d-glucopyranosyloxymethyluracil (base J), was
      identified in the nuclear DNA of Trypanosoma brucei. Base J is the first
      hypermodified base found in eukaryotic DNA. It is present in all kinetoplastid
      flagellates analyzed and some unicellular flagellates closely related to
      trypanosomatids, but it has not been found in other protozoa or in metazoa. J is
      invariably present in the telomeric repeats of all organisms analyzed. Whereas in
      Leishmania nearly all J is telomeric, there are other repetitive DNA sequences
      containing J in T. brucei and T. cruzi, and most J is outside telomeres in
      Euglena. The biosynthesis of J occurs in two steps: First, a specific thymidine
      in DNA is converted into hydroxymethyldeoxyuridine (HOMedU), and then this HOMedU
      is glycosylated to form J. This review discusses the identification and
      localization of base J in the genome of kinetoplastids, the enzymes involved in J
      biosynthesis, possible biological functions of J, and J as a potential target for
      chemotherapy of diseases caused by kinetoplastids.

PMID- 18729735
TI  - A case study for microbial biodegradation: anaerobic bacterial reductive
      dechlorination of polychlorinated biphenyls-from sediment to defined medium.
AB  - The history of anaerobic microbial polychlorinated biphenyl (PCB) dechlorination
      is traced over 20 years using a case study of PCB dechlorination in the
      Housatonic River (Massachusetts) as an example. The history progresses from the
      characterization of the PCBs in the sediment, to cultivation in sediment
      microcosms, to the identification of four distinct types of PCB dechlorination,
      to a successful field test, to the cultivation in defined medium of the organisms
      responsible for extensive dechlorination of Aroclor 1260, and finally to the
      identification of a Dehalococcoides population that links its growth to the
      dechlorination of Aroclor 1260. Other PCB dechlorinators have also been
      identified. Two bacterial strains, o-17 and DF-1, that link their growth to the
      dechlorination of several PCB congeners belong to a novel clade of putative
      dechlorinating bacteria within the phylum Chloroflexi. Dehalococcoides
      ethenogenes strain 195 also dechlorinates several PCB congeners when grown on
      chlorinated ethenes. Evidence is mounting that Dehalococcoides and other
      dechlorinating Chloroflexi may play a significant role in the dechlorination of
      commercial PCBs in situ.

PMID- 18729732
TI  - RNA polymerase elongation factors.
AB  - The elongation phase of transcription by RNA polymerase is highly regulated and
      modulated. Both general and operon-specific elongation factors determine the
      local rate and extent of transcription to coordinate the appearance of transcript
      with its use as a messenger or functional ribonucleoprotein or regulatory
      element, as well as to provide operon-specific gene regulation.

PMID- 18729736
TI  - Species diversity and distribution in presence-absence matrices: mathematical
      relationships and biological implications.
AB  - The diversity of sites and the distribution of species are fundamental pieces in
      the analysis of biogeographic and macroecological questions. A link between these
      two variables is the correlation between the species diversity of sites and the
      mean range size of species occurring there. Alternatively, one could correlate
      the range sizes of species and the mean species diversity within those ranges.
      Here we show that both approaches are mirror images of the same patterns,
      reflecting fundamental mathematical and biological relationships. We develop a
      theory and analyze data for North American mammals to interpret range-diversity
      plots in which the species diversity of sites and the geographic range of species
      can be depicted simultaneously. We show that such plots contain much more
      information than traditional correlative approaches do, and we demonstrate that
      the positions of points in the plots are determined to a large extent by the
      average, minimum, and maximum values of range and diversity but that the
      dispersion of points depends on the association among species and the similitude
      among sites. These generalizations can be applied to biogeographic studies of
      diversity and distribution and in the identification of hotspots of diversity and
      endemism.

PMID- 18729737
TI  - The role of PACT in mediating gene induction, PKR activation, and apoptosis in
      response to diverse stimuli.
AB  - PACT, the protein activator of the double-stranded (ds)RNA-activated protein
      kinase (PKR) has been shown to strongly interact with and activate PKR in
      cultured cells and in vitro. To further analyze the functions of PACT we have
      recently generated PACT knockout (KO) mice and described several developmental
      defects that are absent in PKR KO mice. Importantly, PACT has been previously
      suggested to be involved in different signaling pathways that include endoplasmic
      reticulum stress, serum deprivation, growth factor withdrawal, viral infection,
      and cytokine responses. In this study, we have analyzed the contribution of PACT
      to these pathways using cells derived from wildtype (WT) and PACT KO mice.
      Notably, we have been unable to detect any significant differences in the
      responses to stress stimuli comparing WT and PACT KO cells, although we have been
      able to validate the specific interaction between PACT and PKR. Taken together,
      our results reinforce the importance of genetic loss of function analysis to
      infer protein function.

PMID- 18729734
TI  - Viral subversion of apoptotic enzymes: escape from death row.
AB  - To prolong cell viability and facilitate replication, viruses have evolved
      multiple mechanisms to inhibit the host apoptotic response. Cellular proteases
      such as caspases and serine proteases are instrumental in promoting apoptosis.
      Thus, these enzymes are logical targets for virus-mediated modulation to suppress
      cell death. Four major classes of viral inhibitors antagonize caspase function:
      serpins, p35 family members, inhibitor of apoptosis proteins, and viral FLICE
      inhibitory proteins. Viruses also subvert activity of the serine proteases,
      granzyme B and HtrA2/Omi, to avoid cell death. The combined efforts of viruses to
      suppress apoptosis suggest that this response should be avoided at all costs.
      However, some viruses utilize caspases during replication to aid virus protein
      maturation, progeny release, or both. Hence, a multifaceted relationship exists
      between viruses and the apoptotic response they induce. Examination of these
      interactions contributes to our understanding of both virus pathogenesis and the
      regulation of apoptotic enzymes in normal cellular functions.

PMID- 18729738
TI  - Highly expressed dectin-1 on bone marrow-derived dendritic cells regulates the
      sensitivity to beta-glucan in DBA/2 mice.
AB  - Sparassis crispa beta-glucan (SCG) is a major six-branched 1,3-beta-D-glucan in
      S. crispa Fr. showing antitumor activity. We previously found that DBA/1 and
      DBA/2 mice are highly sensitive to SCG in vivo and in vitro. In this study, we
      investigated the effect of SCG on bone marrow-derived dendritic cells (BMDCs) in
      DBA/2 mice in vitro. SCG increased the expression of CD80, MHC class I and MHC
      class II molecules on the cell membrane of BMDCs. SCG induced BMDCs to produce
      interleukin-12p70 (IL-12p70), IL-6, and tumor necrosis factor-alpha (TNF-alpha).
      The magnitude of cytokine induction by SCG in DBA/2 mice was higher than that in
      C57BL/6, BALB/c, C3H/HeN, and C3H/HeJ mice. The expression level of the beta
      glucan receptor, dectin-1, on BMDCs in DBA/2 mice was also highest in DBA/2 among
      these mice. Blocking dectin-1 significantly inhibited the induction of TNF-alpha
      production by SCG. Taken together, these results suggest that the BMDCs from
      DBA/2 mice are highly sensitive to the induction of cytokine production by SCG in
      vitro, and that this sensitivity is related to the expression level of dectin-1.

PMID- 18729739
TI  - Interferon-alpha2b restores the impaired chemotactic activity of peripheral blood
      mononuclear cells from head and neck squamous cell carcinoma patients by
      modulating CXC receptor ligand interaction.
AB  - We have studied the immunomodulatory effects of interferon-alpha2b (IFN-alpha2b)
      in rectification of the dysregulated IFN-gamma-dependent chemokines and their
      receptor CXCR3 splice variants in head and neck squamous cell carcinoma
      peripheral blood mononuclear cells (HNSCC-PBMC). CXCR3 expression was upregulated
      in HNSCC-PBMC, with the demonstration of poor chemotactic function. CXCR3
      upregulation possibly represents the increased synthesis of CXCR3B splice
      variant, without significant change in CXCR3A. Upregulated expression of CXCR3B
      was downregulated following in vitro IFN-alpha2b treatment of HNSCC-PBMC.
      Upregulation of CXCR3A+B by IFN-alpha2b with downregulation of the CXCR3B
      indirectly suggests that the upregulation of the CXCR3A splice variant induces
      cellular migration. On the other hand, the stimulation of PBMC with IFN-alpha2b
      maintains physiological homeostasis of CXCR3 ligands, CXCL10 and CXCL9, and
      increases the secretion of IFN-gamma. The suppressed chemotactic ability of HNSCC
      PBMC could be restored either by in vitro treatment of PBMC with IFN-alpha2b or
      during the use of IFN-alpha2b stimulated PBMC supernatant as a chemoattractant.
      Chemoattraction process is guided at the level of both receptor and its ligands,
      as confirmed by neutralization studies. IFN-alpha2b possibly controls chemotaxis
      by regulating the interaction between CXCL10 and CXCR3A. Neutralization of IFN
      gamma downregulates the IFN-alpha2b mediated CXCL10 release, suggesting the
      active role of IFN-gamma in the transduction of chemotactic signal for the
      migration of cytotoxic T/NK cells at the tumor site.

PMID- 18729740
TI  - A comprehensive evaluation of human plasmacytoid dendritic cells using small
      volumes of human blood.
AB  - Elucidation of the role played by cells of the innate immune system, particularly
      the dendritic cell (DC) populations, has led to a precipitous growth in our
      understanding of immunity to pathogens and foreign antigens. Much of this
      information has been derived from studies using mouse model systems. However,
      mice and human DCs differ drastically in the relative distribution of the toll
      like receptors (TLRs) critical for immune activation. This is particularly true
      for the plasmacytoid DCs (pDCs), which are activated almost exclusively through
      TLR signaling. Variation in this DC subpopulation has been implicated in a number
      of pathological syndromes; therefore, a thorough understanding of their steady
      state and activation profiles in human patients is essential. A number of
      factors, including the relatively low numbers of these cells in blood, have
      precluded careful analysis in clinical trials. To overcome these limitations, we
      have developed a technique for studying the steady state and activation profile
      of pDCs collected from small amounts of human blood. This technique can be
      performed with 10,000 cells to obtain the immune transcriptome of the pDCs
      analyzed by quantitative PCR using amplified RNA. In addition, we have used
      multiplex enzyme-linked immunosorbent assays to measure secreted proteins. We
      demonstrate the validity of this technique and document its potential for use
      with blood from human study populations.

PMID- 18729743
TI  - Dawn and dusk "chorus" in visually communicating Jamaican anole lizards.
AB  - A key hypothesis explaining the existence of dawn and dusk choruses in
      acoustically communicating animals centers on the need to advertise continued
      territorial occupancy after and before a period of nocturnal inactivity. If this
      hypothesis is correct, it follows that similar dawn and dusk choruses should
      occur in territorial animals exploiting other signal modalities. Adult male
      Anolis lizards defend territories by using elaborate head-bobbing displays and
      extensions of a throat fan or dewlap. Males are inactive at night and return to
      their territories at dawn, remaining there until dusk. I quantified the
      production of visual displays as a function of time of day for four species on
      the island of Jamaica: Anolis lineatopus, Anolis sagrei, Anolis grahami, and
      Anolis opalinus. All exhibited dawn and/or dusk peaks in display behavior. These
      patterns have remarkable parallels with the dawn and dusk choruses reported for
      many acoustically communicating animals.

PMID- 18729741
TI  - Cigarette smoke condensate upregulates the gene and protein expression of
      proinflammatory cytokines in human fibroblast-like synoviocyte line.
AB  - Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes that
      produce proinflammatory cytokines, which are implicated in the pathogenesis of
      RA. When human fibroblast-like synoviocytes line MH7A was treated with cigarette
      smoke condensate (CSC), either mainstream or sidestream, expression levels of
      interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, and CYP1A1 mRNA were upregulated
      in both time- and dose-dependent manners. The upregulatory effects of CSC on
      these cytokines were not significantly inhibited by alpha-naphthoflavone, an aryl
      hydrocarbon receptor (AhR) antagonist, suggesting that the effects of CSC were
      independent of AhR. Cycloheximide treatment indicated that the augmenting effect
      of CSC on IL-1alpha, IL-1beta and IL-8, but not IL-6 and CYP1A1, mRNA expression
      requires de novo protein synthesis. CSC also induced cytokines at protein levels
      and further augmented the effects of tumor necrosis factor alpha on induction of
      these cytokines at both mRNA and protein levels. These results support the
      epidemiological studies indicating a strong association between heavy cigarette
      smoking and pathogenesis of RA.

PMID- 18729744
TI  - Michael E. DeBakey, MD.

PMID- 18729745
TI  - Is it time for a telemedicine breakthrough?

PMID- 18729747
TI  - Telethinking with Joan Sullivan Garrett. Interview by Vicki Glaser.

PMID- 18729748
TI  - Innovative programs in telemedicine: the University of Pittsburgh Medical Center
      (UPMC) Stroke Institute Telemedicine Program.

PMID- 18729749
TI  - Text messaging in healthcare: the elephant knocking at the door.

PMID- 18729750
TI  - Virtual visits in a general medicine practice: a pilot study.
AB  - The purpose of this pilot study is to investigate the feasibility, effectiveness,
      and acceptability of a patient-physician real-time encounter using
      videoconferencing technology (a virtual visit) compared to a face-to-face office
      visit in the general medical setting. The three broad aims of the study are (1)
      to compare the physician's ability to make diagnoses in both settings, (2) to
      compare the physician's ability to provide therapy in both settings, and (3) to
      examine both patient and physician satisfaction with both modalities. Thirty
      patients were recruited from a single practice to participate in the study.
      Patients were first interviewed and examined in the virtual setting, and then in
      the face-to-face setting. Both patients and physician were surveyed after each
      visit type with regard to quality of the history, quality of the examination, and
      satisfaction with the experience. The data were analyzed using two-tailed t-tests
      and analysis of variance. Patients significantly preferred the in-person visit
      (4.7 of 5), but were very satisfied with the virtual visit as well (4.1 of 5) (p
      < 0.0001) (scale: 1= poor, 2 = fair, 3 = good, 4 = very good, 5 = excellent).
      Physical examination effectiveness was significantly worse in the virtual visit
      modality (2.3 versus 4.9 for the face-to-face visit, p < 0.0001), but history and
      therapeutic effectiveness were not significantly different. Both patients and the
      physician felt comfortable with the technology: patients 4.1, physician 4.3.
      Results suggest that both patients and the physician found the virtual visit a
      potentially useful alternative to the traditional visit for many medical
      conditions. This may have significant implications for the general medical care
      environment. Patients may benefit from reduced opportunity costs associated with
      physician visits and clinicians may benefit from decrease overhead costs. Further
      research is ongoing to investigate the generalizability of these findings.

PMID- 18729751
TI  - Diagnosis and management of strabismus using telemedicine.
AB  - This study was undertaken to measure the effect of telemedicine consultation for
      diagnosis and treatment planning in cases of strabismus. Telemedicine
      consultation records of all patients on ORBIS Telemedicine Cyber-Sight that
      resulted in a final diagnosis of superior oblique palsy (SOP), Duane syndrome
      (DS), and Brown syndrome (BS) were collected. The following were then determined:
      (1) the clinical characteristics of patients in each category, (2) the diagnosis
      submitted by the doctor requesting consultation compared to the diagnosis
      determined by the mentor, and (3) the treatment plan submitted with the
      consultation request compared to the mentor's suggested plan. The clinical
      characteristics of patients with SOP, DS, and BS were similar to those reported
      in the literature. There were 89 with SOP, 131 with DS, and 50 with BS. Partners
      and mentors agreed on the diagnosis of SOP in 81% of cases, DS in 79% of cases,
      and BS in 72% of cases. Mentors agreed with the partners' proposed treatment plan
      in SOP 35%, DS 55%, and BS 52%. Mentors are likely to change the diagnosis
      proposed by doctors seeking consultation for strabismus in 25% of cases and
      provide a new treatment plan in more than 50% of cases. The clinical
      characteristics of those strabismus entities selected matched those found in the
      literature, making it likely that the cases as viewed on telemedicine presented a
      true clinical picture.

PMID- 18729752
TI  - Evaluation of unmanned airborne vehicles and mobile robotic telesurgery in an
      extreme environment.
AB  - As unmanned extraction vehicles become a reality in the military theater,
      opportunities to augment medical operations with telesurgical robotics become
      more plausible. This project demonstrated an experimental surgical robot using an
      unmanned airborne vehicle (UAV) as a network topology. Because battlefield
      operations are dynamic and geographically challenging, the installation of
      wireless networks is not a feasible option at this point. However, to utilize
      telesurgical robotics to assist in the urgent medical care of wounded soldiers, a
      robust, high bandwidth, low latency network is requisite. For the first time, a
      mobile surgical robotic system was deployed to an austere environment and
      surgeons were able to remotely operate the systems wirelessly using a UAV. Two
      University of Cincinnati surgeons were able to remotely drive the University of
      Washington's RAVEN robot's end effectors. The network topology demonstrated a
      highly portable, quickly deployable, bandwidth-sufficient and low latency
      wireless network required for battlefield use.

PMID- 18729753
TI  - A staged approach evaluation of remotely supervised myofeedback treatment (RSMT)
      in women with neck-shoulder pain due to computer work.
AB  - Remotely supervised myofeedback treatment (RSMT) is a relatively new intervention
      aimed at reducing neck-shoulder pain and disabilities. Subjects are equipped with
      a garment that can be worn under the clothes during daily work. Dry surface
      electrodes incorporated in this garment measure muscle activation (sEMG) of the
      trapezius muscle. The garment is connected to an ambulant device that provides
      feedback to the subject when muscle relaxation is insufficient. sEMG data are
      also sent to a secured server that is accessible by therapists for remote
      counseling purposes. In conformance with the evaluation stages of DeChant, RSMT
      was evaluated on technical feasibility, patient satisfaction, and changes in
      clinical outcomes. In addition, subjects were asked about their willingness to
      pay. The study population consisted of 10 female workers suffering from neck
      shoulder pain related to computer work. Results show that in 78% of the remote
      counseling sessions, sufficient amounts of data were available at the server for
      the therapist to make an assessment of muscle tension needed for the remote
      counseling sessions. Subjects were highly satisfied about the usefulness and ease
      of use of the remote counseling. However, they were less satisfied with the
      technical functioning of the myofeedback system. Eighty percent of the subjects
      reported a reduction in pain intensity and disability directly after RSMT.
      Subjects were willing to contribute a maximum of 200 euro for RSMT. Based on this
      study, it can be concluded that RSMT is technically feasible and induces changes
      in clinical outcomes. However, further improvements to technical functioning and
      research into the clinical effectiveness are needed before this treatment can go
      into real deployment.

PMID- 18729754
TI  - Assessing acquired language disorders in adults via the Internet.
AB  - Aphasia, a language disturbance, frequently occurs following acquired brain
      impairment in adults. Because management of aphasia is often long-term, provision
      of ongoing and equitable access to treatment creates a significant challenge to
      speech-language pathologists (SLPs). This study aimed to determine the validity
      and reliability of assessing aphasia using standardized language assessments via
      an Internet-based videoconferencing system using a bandwidth of 128 kbits/sec.
      Thirty-two participants with aphasia due to stroke or traumatic brain injury were
      assessed simultaneously in either a face-to-face or online-led environment by two
      SLPs. Short forms of the Boston Diagnostic Aphasia Examination (BDAE-3) and the
      Boston Naming Test (BNT, 2nd edition) were administered. An eight-item
      participant satisfaction questionnaire was completed by 15 participants assigned
      to the online-led assessment. Results failed to identify any significant
      differences between the 24 subtest scores of the BDAE-3 and the BNT scores
      obtained in the online and face-to-face test environments (p > 0.01). Weighted
      kappa statistics indicated moderate to very good agreement (0.59-1.00) between
      the two assessors for the 24 subtests and eight rating scales of the BDAE-3, the
      BNT, and for aphasia diagnosis. Good to very good inter- and intra-rater
      reliability for the online assessment was found across the majority of assessment
      tasks. Participants reported high overall satisfaction, comfort level, and audio
      and visual quality in the online environment. This study supports the validity
      and reliability of delivering standardized assessments of aphasia online and
      provides a basis for ongoing development of telerehabilitation as an alternate
      mode of service delivery to persons with aphasia.

PMID- 18729755
TI  - A secure mobile multimedia system to assist emergency response teams.
AB  - Long wait times after injury and greater distances to travel between accident
      scenes and medical facilities contribute to increased, possibly unnecessary
      deaths. This paper describes a mobile emergency system aimed at reducing
      mortality by improving the readiness of hospital personnel, therefore allowing
      for more efficient treatment procedures to be performed when the victim arrives.
      The system is designed to provide a secure transmission of voice, medical data,
      and video in real-time over third-generation cellular networks. Test results
      obtained on a commercial network under real-life conditions demonstrate the
      ability to effectively transmit medical data over 3G networks, making them a
      viable option available to healthcare professionals.

PMID- 18729756
TI  - The design of a health technology assessment system in telepathology.
AB  - Up to a few years ago, the management of the information on the slides (virtual
      slides) in telepathology applications was principally based on the design and
      construction of a few identical and expensive platforms with microscope units and
      software tools for the display and for electronic control (zooming, moving, and
      cutting of images). The development of information technology tools allows the
      diffusion of new visualization strategies and the availability of low cost or
      free visualization proprietary tools. New competitive systems such as client
      server architectures are available in telepathology today. The investigation of
      the new technologies for telepathology is a basic and core aspect in telemedicine
      technology assessment. A new interactive environment to investigate the health
      technology assessment of a telepathology system has been studied. In particular,
      in consideration of previous experience the methodology focused both on the
      senior pathologist and younger student pathologist. Two interactive forms were
      created by a working group: a feedback form and a diagnostic form. The first was
      designed to investigate the technology characteristics and acceptance of the
      telepathology systems. The second tool was designed to investigate the diagnostic
      accuracy on a significant sample of virtual slides by two different groups of
      pathologists (senior and younger students). The acceptance of the methodology was
      very high.

PMID- 18729757
TI  - E-learning and telehealth: measuring your success.
AB  - Organizations that provide training for their employees are interested in
      translating training expenditures into benefits. Even though there are several
      common methodologies that are used to train employees, finding the right
      methodology to stimulate learning and develop a competent workforce while
      reducing fiscal burdens can be challenging. One such method that continues to
      grow in popularity is e-learning. For the purpose of this discussion, e-learning
      refers to Internet-based or online training. The Veterans Health Administration's
      (VHA's) Office of Care Coordination (OCC) was established in July 2003 to oversee
      the national implementation of its telehealth initiatives. As part of this
      implementation, the OCC created a national center, the Sunshine Training Center,
      to work directly with the VHA's Employees Education System (EES) to develop a
      home telehealth Web-based curriculum. After 3 years, the Sunshine Training Center
      and EES initiated an Impact Evaluation Process. Over five hundred staff completed
      the online impact survey. This number represented a 74% response rate. Staff
      responded overwhelmingly in the positive on the benefits of e-learning for
      building telehealth skills.

PMID- 18729758
TI  - Development of an integrated module using a wireless accelerometer and ECG sensor
      to monitor activities of daily living.
AB  - The objective of this work was to develop a wireless electrocardiogram (ECG) and
      acceleration detector powered by an imbedded battery. The module has a connector
      for a three-lead ECG socket and an embedded three-axis accelerometer. It also has
      an a secure digital (SD) memory slot and can store all data with 2 GB memory. The
      system transmits the data using a wireless module to measure ECG and an activity
      transition value. Using the correlation between accelerometer signal and ECG
      signal, the system can determine the activity assessment precisely and also
      detect cardiovascular abnormality.

PMID- 18729759
TI  - Accelerometer sensor module and fall detection monitoring system based on
      wireless sensor network for e-health applications.
AB  - This research implements a wireless accelerometer sensor module and an algorithm
      to determine an individual's posture, activity, and fall. An analog wireless, two
      axis accelerometer sensor module was used. Using a wireless radiofrequency
      module, the accelerometer signal is displayed on a PC-based "Acceloger" (e
      Digitalmed, Seoul, Korea) viewer program. The activities of daily living
      algorithm uses the AC components of the accelerometer signal to determine
      posture, activity, and fall, and posture while standing, sitting, lying, walking,
      running, and so on is determined by the DC component. The performance of 30
      subjects was evaluated by assessing the algorithm and calculating the detection
      rate for postures, motions, and subjects. Using a wireless sensor network in an
      experimental space, subject's postures, motions, and fall monitoring system was
      implemented. In conclusion, this system can be applied to patients such as the
      elderly for activity monitoring and fall detection and also for sports athlete's
      exercise measurement and pattern analysis.

PMID- 18729760
TI  - SMS application using EMG signal of clenching teeth for e-health communication.
AB  - A proposed system using a Short Message Service (SMS) application based on
      electromyography (EMG)-controlled human-computer interface method by clenching
      teeth was evaluated. This system consists of an EMG signal processing device and
      SMS Software module on the PC. We can use SMS by a simple combination of two
      clenching patterns. The purpose of this study is to evaluate easy and comfortable
      communication methods for the disabled and rehabilitation patients as an e-health
      tool.

PMID- 18729761
TI  - Implementation of safety driving system using e-health and telematics technology.
AB  - This research aimed to develop a safety driving system using e-health and
      telematics technology. Biosignal sensors were installed in an automobile to check
      the driver's health status with an automatic diagnosis system providing health
      information to the driver. Measured data were sent to the e-health center through
      a telematics device, and a medical doctor analyzed these data, sending diagnosis
      and prescription information to the driver. This system recognizes the driver's
      sleeping, drinking impairment, excitability, and fatigue using biosensors. The
      system initially provides alerts in the automobile. It also controls the driving
      environment in the car, searches for a highway service area using Global
      Positioning System (GPS), and provides additional information for safety driving.
      If a car accident has occurred, it makes an emergency call to the nearest
      hospital, emergency center, and insurance company. A conceptual and prototype
      model for an imbedded system is presented with initial data for driver condition.
      Such a system could prevent car accidents caused by drivers driving while
      intoxicated and falling asleep at the wheel using the driver's biosignals
      measured by biosensors. The system can provide various e-health services using a
      telematics system to enhance the technical compatibility of the automobile.

PMID- 18729762
TI  - Developing a National Inventory of Telehealth Resources for Rapid and Effective
      Emergency Medical Care: a white paper developed by the American Telemedicine
      Association Emergency Preparedness and Response Special Interest Group.

PMID- 18729764
TI  - Knockout serum replacement (KSR) has a suppressive effect on Sendai virus
      mediated transduction of cynomolgus ES cells.
AB  - Sendai virus (SeV) vectors can introduce foreign genes efficiently and stably
      into primate embryonic stem (ES) cells. For the application of these cells, the
      control of transgene expression is important. Cynomolgus ES cells transduced with
      a SeV vector expressing the green fluorescent protein (GFP) gene were propagated
      in Knockout serum replacement (KSR)-supplemented medium, used widely for the
      serum-free culture of ES cells, and growth and transgene expression were
      evaluated. The SeV vector-mediated GFP expression was suppressed in the KSR
      supplemented medium, although it was stable in regular fetal bovine serum (FBS)
      supplemented medium. Propagation in the KSR-supplemented medium eventually
      resulted in a complete suppression of GFP expression and eradication of the SeV
      genome. The inhibitory effect of KSR on the transduction was attributable to the
      positive selection of untransduced ES cells in addition to the removal of the SeV
      vector from transduced cells. KSR also reduced the efficiency of the
      transduction. SeV vector-mediated transgene expression in ES cells was suppressed
      in the KSR-supplemented medium. Although the suppression is limited in specified
      cells such as ES cells, these findings will help elucidate how to control
      transgene expression.

PMID- 18729765
TI  - Contribution of shivering and nonshivering thermogenesis to thermogenic capacity
      for the deer mouse (Peromyscus maniculatus).
AB  - Small mammals that are active all year must develop ways to survive the cold
      winters. Endotherms that experience prolonged cold exposure often increase their
      thermogenic capacity. Thermogenic capacity incorporates basal metabolic rate
      (BMR), nonshivering thermogenesis (NST), and shivering thermogenesis (ST).
      Increasing the capacity of any of these components will result in increased
      thermogenic capacity. It is often thought that NST should be the most plastic
      component of thermogenic capacity and as such is the most likely to increase with
      cold acclimation. We used deer mice to test this hypothesis by acclimating 27
      animals to one of two temperatures (5 degrees or 22 degrees C) for 8 wk. We then
      measured and compared values for thermogenic capacity--BMR, ST, and NST--between
      the two groups. Thermogenic capacity and NST increased by 21% and 42%,
      respectively, after cold acclimation. Neither BMR nor ST showed any change after
      acclimation. Therefore, it appears that deer mice raise their thermogenic
      capacity in response to prolonged cold by altering NST only.

PMID- 18729766
TI  - Bart's familiar quotations: the enduring biological wisdom of George A.
      Bartholomew.
AB  - George A. Bartholomew was one of the most influential organismal biologists of
      the twentieth century. His insights and research were fundamental to the
      establishment and growth of physiological ecology and evolutionary physiology. In
      the process of fostering that area of science, he created a body of literature
      that is striking in the clarity of its thought and presentation. Here we present
      some of his most insightful and important quotations, group them thematically,
      and comment on their original context and their continuing relevance.

PMID- 18729767
TI  - Transgenic-cloned pigs systemically expressing red fluorescent protein, Kusabira
      Orange.
AB  - Genetically engineered pigs with cell markers such as fluorescent proteins are
      highly useful in lines of research that include the tracking of transplanted
      cells or tissues. In this study, we produced transgenic-cloned pigs carrying a
      gene for the newly developed red fluorescent protein, humanized Kusabira-Orange
      (huKO), which was cloned from the coral stone Fungia concinna. The nuclear
      transfer embryos, reconstructed with fetal fibroblast cells that had been
      transduced with huKO cDNA using retroviral vector D Delta Nsap, developed
      efficiently in vitro into blastocysts (28.0%, 37/132). Nearly all (94.6%, 35/37)
      of the cloned blastocysts derived from the transduced cells exhibited clear huKO
      gene expression. A total of 429 nuclear transfer embryos were transferred to four
      recipients, all of which became pregnant and gave birth to 18 transgenic-cloned
      offspring in total. All of the pigs highly expressed huKO fluorescence in all of
      the 23 organs and tissues analyzed, including the brain, eyes, intestinal and
      reproductive organs, skeletal muscle, bone, skin, and hoof. Furthermore, such
      expression was also confirmed by histological analyses of various tissues such as
      pancreatic islets, renal corpuscles, neuronal and glial cells, the retina,
      chondrocytes, and hematopoietic cells. These data demonstrate that transgenic
      cloned pigs exhibiting systemic red fluorescence expression can be efficiently
      produced by nuclear transfer of somatic cells retrovirally transduced with huKO
      gene.

PMID- 18729768
TI  - Development and validation of a highly efficient protocol of porcine somatic
      cloning using preovulatory embryo transfer in peripubertal gilts.
AB  - The efficiency of porcine somatic nuclear transfer (born piglets/transferred
      embryos) is low. Here, we report a highly efficient protocol using peripubertal
      gilts as recipients synchronized to ovulate approximately 24 h after transfer of
      cloned embryos. Retrospectively, we compared the efficiency of two different
      synchronization protocols: In group 1, recipient animals were synchronized to
      ovulate approximately 6 h prior to surgical embryo transfer while in group 2 the
      animals were treated to ovulate 24 h after embryo transfer. In total, 1562 cloned
      embryos were transferred to 12 recipients in group 1; two of them became pregnant
      (16.7%). One pregnancy was lost on day 32, the second pregnancy went to term, and
      led to the birth of one healthy piglet after Cesarean section. In group 2, 1531
      cloned embryos were transferred to 12 recipients. Nine recipients (75.0%) became
      pregnant as determined by ultrasound scanning on day 25. All pregnancies went to
      term and delivered a total of 47 live-born piglets. The cloning efficiency of
      both groups differed significantly (group 1: 0.1%, group 2: 3.1%, p < 0.05). This
      modified protocol was then applied in subsequent experiments using different
      types of transgenic and nontransgenic donor cells with similar success rates.
      Results show that this protocol is robust and highly reproducible, and can thus
      be employed for routine production of cloned pigs.

PMID- 18729769
TI  - Isolation of progenitor cells from GFP-transgenic pigs and transplantation to the
      retina of allorecipients.
AB  - Work in rodents has demonstrated that progenitor transplantation can achieve
      limited photoreceptor replacement in the mammalian retina; however, replication
      of these findings on a clinically relevant scale requires a large animal model.
      To evaluate the ability of porcine retinal progenitor cells to survival as
      allografts and integrate into the host retinal architecture, we isolated donor
      cells from fetal green fluorescent protein (GFP)-transgenic pigs. Cultures were
      propagated from the brain, retina, and corneo-scleral limbus. GFP expression
      rapidly increased with time in culture, although lower in conjunction with
      photoreceptor markers and glial fibrillary acid protein (GFAP), thus suggesting
      downregulation of GFP during differentiation. Following transplantation, GFP
      expression allowed histological visualization of integrated cells and extension
      of fine processes to adjacent plexiform layers. GFP expression in subretinal
      grafts was high in cells expressing vimentin and lower in cells expressing
      photoreceptor markers, again consistent with possible downregulation during
      differentiation. Cells survived transplantation to the injured retina of
      allorecipients at all time points examined (up to 10 weeks) in the absence of
      exogenous immune suppression without indications of rejection. These findings
      demonstrate the feasibility of allogeneic progenitor transplantation in a large
      mammal and the utility of the pig in ocular regeneration studies.

PMID- 18729770
TI  - Magnetic resonance imaging detects and predicts early brain injury after
      subarachnoid hemorrhage in a canine experimental model.
AB  - The canine double hemorrhage model is an established model to study cerebral
      vasospasm, the late sequelae of subarachnoid hemorrhage (SAH). The present study
      uses magnetic resonance imaging (MRI) to examine the recently reported early
      brain injury after SAH. Double hemorrhage SAH modeling was obtained by injecting
      0.5 mL/kg of autologous arterial blood into the cisterna magna of five adult
      mongrel dogs on day 0 and day 2, followed by imaging at day 2 and day 7 using a
      4.7-Tesla (T) scanner. White matter (WM) showed a remarkable increase in T2
      values at day 2 which resolved by day 7, whereas gray matter (GM) T2 values did
      not resolve. The apparent diffusion coefficient (ADC) values progressively
      increased in both WM and GM after SAH, suggestive of a transition from vasogenic
      to cytotoxic edema. Ventricular volume also increased dramatically. Prominent
      neuronal injury with Nissl's staining was seen in the cortical GM and in the
      periventricular tissue. Multimodal MRI reveals acute changes in the brain after
      SAH and can be used to non-invasively study early brain injury and normal
      pressure hydrocephalus post-SAH. MR can also predict tissue histopathology and
      may be useful for assessing pharmacological treatments designed to ameliorate
      SAH.

PMID- 18729772
TI  - Examination of a second region of the HIV type 1 genome reveals additional cases
      of superinfection.
AB  - HIV-1 superinfection may occur at a rate similar to that of initial infection,
      raising concerns for HIV-1 vaccine strategies predicated on eliciting immune
      responses similar to those in natural infection. Because of the high rate of
      recombination during HIV-1 replication, studies examining only one region of the
      HIV-1 genome are likely to miss cases of HIV-1 superinfection. We examined HIV-1
      gag sequences from 14 high-risk Kenyan women in whom superinfection was not
      detected in a previous study of env sequences. We detected two additional cases
      of HIV-1 superinfection: one intersubtype superinfection that occurred between
      1046 and 1487 days postinfection (DPI) and one intrasubtype superinfection that
      occurred between 341 and 440 DPI. Our results suggest that studies that examine
      only small genome regions may lead to underestimates of the risk of
      superinfection, highlighting the need for more extensive studies examining
      multiple regions of the HIV-1 genome.

PMID- 18729771
TI  - Interplay of reverse transcriptase inhibitor therapy and gag p6 diversity in HIV
      type 1 subtype G and CRF02_AG.
AB  - Abstract The gag p6 region of HIV-1 has various nonsubstitutionary mutations,
      including insertions, duplications, deletions, and premature stop codons. Studies
      have linked gag p6 mutations to reduced susceptibility to antiretroviral therapy
      in HIV-1 subtype B. This study examined the relationship between antiretroviral
      therapy and gag p6 diversity in HIV-1 CRF02_AG and subtype G. p6 data were
      generated for secondary analyses following Viroseq genotyping of pol gene
      sequences in plasma samples from HIV-1-infected Nigerians on reverse
      transcriptase inhibitor therapy, with virologic failure (repeat VL > 2000
      copies/ml). p6 sequence chromatograms were available for 40 CRF02_AG and 43
      subtype G-infected individuals. Subjects who had not received their supply of
      antiretroviral drugs for at least 2 months prior to the plasma sampling were
      classified as nonadherent. p6 sequences from therapy-adherent individuals had
      more nonsubstitutionary mutations than sequences from drug-naive individuals (p =
      0.0005). The P5L/T mutation was inversely correlated with the presence of K27Q/N
      in p6, with each mutation being more prominent in subtype G and CRF02_AG,
      respectively. The data also suggested that P5L/T may be a compensatory mutation
      for the loss of an essential phosphorylation site in p6. In addition, there was
      an inverse association between P5L/T mutations in p6 and thymidine analog
      mutations in reverse transcriptase (p = 0.0001), and drug nonadherence was
      associated with an 8-fold lower risk of having a nonsubstitutionary mutation in
      p6 (95% CI = 1.27-52.57). Our data suggest that antiretroviral therapy influences
      gag p6 diversity, but further studies are needed to clarify these observations.

PMID- 18729773
TI  - No major differences in the functional profile of HIV Gag and Nef-specific CD8+
      responses between long-term nonprogressors and typical progressors.
AB  - The mechanism explaining the failure of HIV-specific CD8(+) T cell responses to
      successfully control HIV replication remains elusive. A total of 83 drug-naive
      HIV-infected individuals, 27 of whom were long-term nonprogressors (LTNP), was
      examined. The ability of CD8(+) T lymphocytes to produce three different
      cytokines (MIP-1beta, TNF-alpha, IL-2) in response to HIV Gag and Nef peptides
      and to polyclonal stimuli and the ability of HIV-specific CD8(+) T cells to
      expand in vitro were evaluated by multiparameter flow cytometry. In response to
      polyclonal stimulation, LTNP presented significantly higher levels of several
      CD8(+) T cell subsets than progressors. While most patients presented detectable
      Gag and Nef-specific CD8(+) responses, no significant differences in any of the
      CD8(+) functional T cell subsets were recognized when comparing LTNP and
      progressors. HIV responses were dominated by cells producing only MIP-1beta or
      TNF-alpha, being similar in LTNP and progressors. However, expansion of HIV
      specific CD8(+) T cells was more frequent in LTNP than progressors, especially
      for cells producing MIP-1beta. LTNP show higher levels of CD8(+) responses
      against polyclonal stimuli than progressors. However, HIV-specific CD8(+)
      responses do not differ between them except for a more preserved ability of cells
      from LTNP to expand in vitro.

PMID- 18729774
TI  - Comparison of ABC transporter modulation by atazanavir in lymphocytes and human
      brain endothelial cells: ABC transporters are involved in the atazanavir-limited
      passage across an in vitro human model of the blood-brain barrier.
AB  - Efflux pumps, P-glycoprotein (P-gp), multidrug resistance-associated proteins
      (MRPs), and breast cancer resistance protein (BCRP) have been shown to extrude
      HIV protease inhibitors from cells. These transporters are present on many
      barrier sites such as the blood-brain barrier (BBB) and on many circulating cells
      such as lymphocytes, and could reduce protease inhibitor concentration in
      sanctuary or HIV-1 target sites. This study compares the potential of the
      antiretroviral drug atazanavir to modulate P-gp and MRP expression and function
      in total lymphocytes and in human fetal brain endothelial cells (HBMECs). We
      address the question of atazanavir transport across the human BBB. Following
      incubation with atazanavir, P-gp and MRP1 expression was determined by direct
      immunofluorescence. Transporter function was assessed by measuring fluorescent
      dye efflux, either with or without specific inhibitors. Atazanavir substrate
      properties were determined by transport quantification through a validated in
      vitro human BBB model. Our results show that in contrast to HBMECs, in
      lymphocytes, atazanavir has no effect on MRP1 and P-gp expression. However, there
      were overall changes in P-gp function increasing its activity in lymphocytes and
      HBMECs. Using the in vitro human BBB model, we confirm the interaction of
      atazanavir with P-gp, MRPs, and BCRP in preventing its passage across this
      barrier and thus its entry into the central nervous system.

PMID- 18729776
TI  - Latitudinal distribution, migration, and testosterone levels in birds.
AB  - Tropical bird species usually have lower testosterone (T) levels during breeding
      than temperate species. However, the potential mechanisms behind the positive
      interspecific correlation between T and latitude remain unexplored. In a
      comparative study of more than 100 bird species, we examined whether social
      constraints during male-male competition arising from migration and breeding
      synchrony are responsible for the latitude effects. Species that breed at higher
      latitudes are more likely to migrate and experience more intense intrasexual
      competition upon spring arrival than nonmigrant species from lower latitudes.
      Additionally, species from higher latitudes cope with shorter breeding seasons
      and thus with more synchronous breeding, which selects for high T titers via
      increased male-male conflicts. Accordingly, peak T levels were associated with
      migration and the duration of the egg laying period that reflects breeding
      synchrony. Because migration and breeding synchrony were related to latitudinal
      distribution, they appear to be important components of the latitude effects on
      T. A multivariate model controlling for covariation of predictor variables
      revealed that latitude remained the strongest predictor of peak T. Therefore,
      selection due to migration and breeding synchrony may partially cause the
      latitude effect, but other geographically varying factors may also play a role in
      mediating peak T levels at different latitudes.

PMID- 18729775
TI  - The TRAIL of helpless CD8+ T cells in HIV infection.
AB  - Our understanding of how CD4(+) T cells can regulate CD8(+) T cell responses in
      HIV infection is still incomplete. Recent evidence obtained in mice suggests that
      CD4(+) T cell help is required for efficient CD8(+) T cell-mediated immunity in
      chronic infection: CD8(+) T cells primed in the absence of such help release the
      TNF-related apoptosis-inducing ligand TRAIL and undergo apoptosis. Using a novel
      ELISPOT assay, in the present study we show that CD8(+) T cells are also a source
      of the antigen-specific TRAIL response in HIV-infected patients with CD4(+) T
      cell counts below 200. In patients with CD4(+) T cell counts above 200 TRAIL was
      not detectable. Accordingly, antigens to which patients have likely been exposed
      when CD4(+) T cell levels were high (e.g., influenza, CMV, and EBV) did not
      induce TRAIL. Within the HIV-positive donor population with low CD4(+) T cell
      counts a dissociation of the interferon-gamma (IFN-gamma) and TRAIL response to
      different HIV peptide epitopes was detectable suggesting impaired immunity to
      antigens that triggered TRAIL in the absence of IFN-gamma. Our findings emphasize
      that "helpless" CD8(+) T cells, i.e., cells that have been primed in the absence
      of CD4(+) T cell help, may play a crucial role in HIV infection. A "helpless"
      phenotype may impair CD8(+) T cell control of HIV and other infections and
      possibly contribute to the depletion of CD4(+) T cells via apoptosis.
      Immunizations and infections in this "helpless" state might result in ineffective
      CD8(+) T cell responses.

PMID- 18729777
TI  - Increasing doses of an inactivated influenza A/H1N1 vaccine induce increasing
      levels of cross-reacting antibody to subsequent, antigenically different,
      variants.
AB  - Immunization approaches that will broaden antibody responses to antigenically
      different variants of influenza viruses are needed because vaccine strains do not
      always match the viruses that circulate during the subsequent epidemic. Sera
      collected from subjects who were vaccinated with various doses of influenza
      A/Taiwan/86 vaccine were assayed for the levels of antibody against 3 subsequent,
      antigenically different, A/H1N1 variants. Dose-related increases in antibody
      responses to all 4 viruses were observed, even against a virus appearing >10
      years after vaccination. Increasing the influenza vaccine dosage safely and
      predictably enhanced antibody responses to the vaccine virus and to subsequent,
      antigenically different, influenza A/H1N1 variants.

PMID- 18729778
TI  - Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to
      respiratory tract infections in young men.
AB  - BACKGROUND: Mannose-binding lectin (MBL) is an important component of innate
      immunity, and its deficiency is associated with susceptibility to recurrent
      infections. METHODS: This exploratory study investigated the association of serum
      MBL concentrations and MBL2 gene polymorphisms with respiratory tract infections
      in young men. We genotyped 6 single-nucleotide polymorphisms (SNPs) in the
      promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (variant alleles B, C, and
      D and wild-type allele A) of the MBL2 gene by real-time polymerase chain reaction
      and measured serum MBL concentrations in 111 Finnish military recruits with
      asthma and 362 without. RESULTS: An MBL level below the median concentration was
      a significant risk factor for infections (asthma status-adjusted odds ratio [OR],
      2.5 [95% confidence interval {CI}, 1.4-4.5]). Among the 6 SNPs, there was a
      significant association between the promoter Y/Y genotype and infections (OR, 2.3
      [95% CI, 1.2-4.4]) and a borderline significant association between exon 1
      variant alleles and infections (OR, 1.7 [95% CI, 0.9-3.1]), after adjustment for
      asthma status. CONCLUSION: These preliminary results suggest, for the first time,
      an association between MBL level and respiratory tract infections in young men
      and a possible association between infections and MBL2 polymorphisms.

PMID- 18729779
TI  - Interferon and interferon-induced chemokine expression is associated with control
      of acute viremia in West Nile virus-infected blood donors.
AB  - To understand early host responses controlling West Nile virus (WNV) infection,
      acutely viremic blood donors, identified by nucleic acid amplification testing,
      were enrolled and monitored for RNA-clearance and WNV-specific IgM and IgG
      antibodies. Viral load and chemokine and cytokine assays were performed on serial
      samples from donors whose index and first follow-up samples tested negative for
      IgM. A total of 84% of the specimens obtained from viremic donors before IgM/IgG
      seroconversion demonstrated a decreasing viral load. Levels of interferon (IFN)
      alpha were significantly increased before IgM seroconversion, relative to those
      in control specimens. CXCL10 and CCL2 were significantly elevated in donor
      specimens obtained before IgM seroconversion, compared with those obtained after
      IgM seroconversion. These findings suggest that IFN-mediated innate immunity
      plays a key role in initial control of WNV replication.

PMID- 18729780
TI  - Panton-Valentine leukocidin is not a virulence determinant in murine models of
      community-associated methicillin-resistant Staphylococcus aureus disease.
AB  - Increases in the incidence and severity of community-associated methicillin
      resistant Staphylococcus aureus (CA-MRSA) infections have spawned efforts to
      define unique virulence properties among prevalent strains. Panton-Valentine
      leukocidin (PVL), a pore-forming cytotoxin, has garnered attention because of its
      epidemiologic association with CA-MRSA. Using both the clinical isolate LAC,
      which is representative of the epidemic USA300 strain, and its isogenic PVL
      negative strain in murine models of staphylococcal skin infection and pneumonia,
      we expanded upon recent studies by assessing the contribution of PVL in the
      genetic background of BALB/c mice. The data presented in this report support the
      observation that PVL does not contribute to the pathogenesis of staphylococcal
      infection of mice.

PMID- 18729781
TI  - Repeated treatments with albendazole enhance Th2 responses to Ascaris
      Lumbricoides, but not to aeroallergens, in children from rural communities in the
      Tropics.
AB  - Geohelminth infections are associated with modulation of immunity to parasite
      antigens and aeroallergens. To investigate the possibility that this modulation
      is affected by anthelmintic treatment, we compared cytokine responses in children
      who were treated with repeated doses of albendazole over 1 year versus those in
      children who had were not treated. Whole-blood samples were cultured with Ascaris
      antigen and house dust mite and cockroach allergens, and levels of interleukin
      (IL)-5, IL-13, interferon-gamma, and IL-10 were measured. Anthelmintic treatment
      was associated with enhanced production of Th2 cytokines in response to parasite
      antigen but did not affect responses to aeroallergens. The data indicate that
      long-term treatment may be associated with increased Th2 antiparasite immunity.

PMID- 18729782
TI  - Cholera toxin-specific memory B cell responses are induced in patients with
      dehydrating diarrhea caused by Vibrio cholerae O1.
AB  - BACKGROUND: Infection with Vibrio cholerae induces durable immunity against
      subsequent disease, a process hypothesized to reflect anamnestic immune responses
      at the intestinal mucosa. The presence of antigen-specific memory B cells may
      therefore be a more direct measure of protection than serum antibody responses.
      METHODS: We measured immunoglobulin (Ig) G memory B cells specific to cholera
      toxin B subunit (CTB) in 14 patients up to 90 days after V. cholerae O1
      infection, by polyclonal stimulation of peripheral blood mononuclear cells
      followed by standard enzyme-linked immunospot assay. RESULTS: All patients
      generated CTB-specific IgG memory B cell responses by day 30 (mean, 0.10% of
      total circulating IgG memory B cells; range, 0.037%-0.28%), which persisted to
      day 90 (mean, 0.07%; range, 0.003%-0.27%). In contrast, circulating CTB-specific
      IgG antibody-secreting cells and serum vibriocidal and anti-CTB antibody
      responses peaked on day 7 and declined to undetectable or significantly lower
      levels by day 90. CONCLUSIONS: CTB-specific IgG memory B cell responses are
      detectable in the circulation at least 3 months after V. cholerae O1 infection
      and remain measurable even after serum antibody titers have declined to
      undetectable or considerably lower levels. This suggests that antigen-specific
      memory B cells may be an important long-term marker of the immune response to
      cholera.

PMID- 18729783
TI  - Virus and antibody dynamics in acute west nile virus infection.
AB  - BACKGROUND: The dynamics of the early stages of West Nile virus (WNV) infection
      can be assessed by follow-up studies of viremic blood donors. METHODS: A total of
      245 donors with WNV viremia were followed up weekly for 4 weeks and then monthly
      for up to 6 additional months or until seroconversion. Plasma samples were tested
      for WNV RNA by transcription-mediated amplification (TMA) and for WNV-specific
      IgM and IgG antibodies. RNA persistence was investigated by 6 replicate TMA
      tests; samples that were viremic for >40 days were tested for WNV-neutralizing
      activity. Follow up of 35 additional viremic donors for up to 404 days was
      conducted to evaluate persistence of WNV-specific antibody. RESULTS: The median
      time from RNA detection to IgM seroconversion was 3.9 days; to IgG
      seroconversion, 7.7 days; to RNA negativity by single-replicate TMA, 13.2 days;
      and to RNA negativity by 6-replicate TMA, 6.1 additional days after results of
      single-replicate TMA are negative. For 4 donors in whom RNA persisted for >40
      days after the index donation, all samples obtained after this threshold were
      also positive for WNV IgG and neutralizing activity. The mean times to IgM and
      IgA negativity were 156 and 220 days, respectively. CONCLUSIONS: IgM and IgG
      develop rapidly after viremia and before RNA levels become undetectable, which
      occurred a mean of 13.2 days after the index donation among donors in this study.
      WNV RNA detection by replicate TMA rarely persists for >40 days after the index
      donation and is accompanied by WNV-specific neutralizing antibody, consistent
      with an absence of WNV transmission via transfusion of seropositive blood
      components.

PMID- 18729784
TI  - Bedeviling details.

PMID- 18729785
TI  - The need for a regen industry voice.

PMID- 18729786
TI  - More than a cover: epicardium as a novel source of cardiac progenitor cells.

PMID- 18729789
TI  - Interview. From canaries to the clinic.

PMID- 18729791
TI  - Stemina biomarker discovery.
AB  - Stemina Biomarker Discovery was established in 2006 to commercialize technology
      developed by Dr Gabriela Cezar at the University of Wisconsin (WI, USA).
      Stemina's cell-based assays arise from the strategic convergence of two cutting
      edge technologies: metabolomics and human embryonic stem (hES) cells. Stemina
      analyzes the small molecules secreted by hES cells and differentiated cell types
      such as neural and heart cells derived from hES cells by liquid chromatography
      mass spectrometry at its state-of-the-art facilities in Madison, WI, USA.
      Stemina's first technology platform has identified a dynamic set of small
      molecules in the extracellular secretome of hES cells secreted in response to
      exposure to a library of known teratogens. Alterations to small molecules in the
      biochemical pathway(s) of hES cells are mapped in silico to identify biomarkers
      of toxicity for drug screening and development in an all human system. These
      small human molecules may then be translated in vivo as biomarkers of toxic
      response and disease.

PMID- 18729792
TI  - Long-term durability, tissue regeneration and neo-organ growth during skeletal
      maturation with a neo-bladder augmentation construct.
AB  - AIMS: To comparatively evaluate bladder regeneration following 80% cystectomy and
      augmentation using a synthetic biopolymer with autologous urothelial and smooth
      muscle cells (autologous neo-bladder augmentation construct [construct]) or
      autotransplantation of native bladder (reimplanted native urinary bladder
      [reimplant]) in canines. MATERIALS & METHODS: Voiding function, urodynamic
      assessment and neo-organ capacity-to-body-weight ratio (C:BW) were assessed
      longitudinally for a total of 24 months following trigone-sparing augmentation
      cystoplasty in juvenile canines. RESULTS: Within 30 days postimplantation,
      hematology and urinalysis returned to baseline. Constructs and reimplants yielded
      neo-organs with statistically equivalent urodynamics and histology. Linear
      regression analysis of C:BW showed that constructs regained baseline slope and
      continued to adapt with animal growth. CONCLUSIONS: Constructs and reimplants
      regained and maintained native bladder histology by 3 months, capacity at 3-6
      months and compliance by 12-24 months. Furthermore, construct C:BW demonstrated
      the ability of regenerated bladder to respond to growth regulation.

PMID- 18729793
TI  - Hair morphogenesis in vitro: formation of hair structures suitable for
      implantation.
AB  - AIM: To develop a construct through which implanted follicular cells will
      efficiently cause hair regeneration for the treatment of androgenetic alopecia.
      MATERIALS & METHODS: Follicular dermal and epidermal cells isolated from
      embryonic mouse skin were formed into aggregates. The aggregates were incubated
      in culture for 5-7 days and then implanted intradermally into athymic mice.
      RESULTS: During culture, mixed cell aggregates developed into hair-like
      structures, termed 'proto-hairs'. Proto-hairs contained structures that resembled
      normal hair components, such as dermal papillae, hair matrix and rudimentary hair
      shafts. When implanted into mouse skin, they developed further into mature hair
      follicles capable of prolonged growth. CONCLUSION: Mixed aggregates of murine
      follicular cells have the ability to develop in culture into proto-hairs that
      retain the ability to fully develop into hair follicles after implantation. Proto
      hairs from human cells could provide a convenient and practical means by which
      follicular cells could be implanted for efficient hair regeneration to treat hair
      loss.

PMID- 18729794
TI  - Robust generation of hemangioblastic progenitors from human embryonic stem cells.
AB  - BACKGROUND: Human embryonic stem cells (hESCs) are a potentially inexhaustible
      source of cells for replacement therapy. However, successful preclinical and
      clinical progress requires efficient and controlled differentiation towards the
      specific differentiated cell fate. METHODS: We previously developed a strategy to
      generate blast cells (BCs) from hESCs that were capable of differentiating into
      vascular structures as well as into all hematopoietic cell lineages. Although the
      BCs were shown to repair damaged vasculature in multiple animal models, the large
      scale generation of cells under these conditions was challenging. Here we report
      a simpler and more efficient method for robust generation of hemangioblastic
      progenitors. RESULTS: In addition to eliminating several expensive factors that
      are unnecessary, we demonstrate that bone morphogenetic protein (BMP)-4 and VEGF
      are necessary and sufficient to induce hemangioblastic commitment and development
      from hESCs during early stages of differentiation. BMP-4 and VEGF significantly
      upregulate T-brachyury, KDR, CD31 and Lmo2 gene expression, while dramatically
      downregulating Oct-4 expression. The addition of basic FGF during growth and
      expansion was found to further enhance BC development, consistently generating
      approximately 1 x 10(8) BCs from one six well plate of hESCs. CONCLUSION: This
      new method represents a significantly improved system for generating
      hemangioblasts from hESCs, and although simplified, results in an eightfold
      increase in cell yield.

PMID- 18729795
TI  - Comparative analysis of highly defined proteases for the isolation of adipose
      tissue-derived stem cells.
AB  - BACKGROUND: Before the potential of adipose tissue-derived stem cells can fully
      be exploited for a broad scope of tissue-engineering and cell-based therapeutical
      applications, an effective and reproducible method for isolation is needed. AIM:
      To comparatively analyze five highly defined protease formulations, Blendzyme 1
      4, liberase H1 and a crude collagenase mixture in the course of digestion that
      consisted of three 1-h intervals. METHODS: The resulting digests of human adipose
      tissue aspirates were evaluated for the yield of nucleated cells, viability and
      frequency of specific lineages, in particular CD90, CD34 and CD45, by flow
      cytometry. The functionality of the cells was assessed as to the colony-forming
      capacity in limiting dilution assays. RESULTS: Based on all evaluation criteria,
      Blendzymes 1 and 2 and liberase H1 demonstrated a superior performance and
      highest consistency. Blendzyme 3 clearly underperformed compared with all other
      enzymes, and the performance of the rest of enzymes appeared erratic. As for the
      length of digestion, a 2-h interval appeared optimal when weighing both the yield
      and functionality of the cells in the stromal vascular fractions obtained from
      different adipose tissue samples. CONCLUSION: Our results demonstrate that the
      highly purified proteases provide a valuable alternative to crude collagenase
      preparations, especially in scenarios where a high definition and reproducibility
      of the digestion process is of importance.

PMID- 18729796
TI  - Strategies for regeneration of the intervertebral disc.
AB  - Low back pain resulting from degenerative disc disease is the most common cause
      of disability in the UK. Current low back pain treatments are aimed at either
      treating the symptoms of pain, or removing the source of pain itself, but do not
      address the biological basis of the disease. Our increasing understanding of the
      molecular biological basis for degenerative disc disease has enabled the
      development of strategies aimed at tackling the causes of degeneration. Here we
      review the progress that has been made in strategies using cells, biomaterials
      and growth factors aimed at regenerating the human intervertebral disc.

PMID- 18729797
TI  - Human bone marrow native mesenchymal stem cells.
AB  - The adult bone marrow (BM) has been generally considered to be composed of
      hematopoietic tissue and the associated supporting stroma. There is accumulating
      evidence that a subset of multipotential cells exists within the latter
      compartment, commonly referred to as mesenchymal stem cells (MSCs). These cells
      can be easily expanded ex vivo and induced to differentiate into skeletal
      connective tissues, thereby emerging as attractive candidates for various
      therapeutic applications. Despite the extensive in vitro characterization of
      MSCs, at present, little is known about their in vivo properties or anatomical
      location. Here we review the efficacy of the different surface markers used to
      isolate BM MSCs and highlight current data suggesting that BM MSCs in situ are
      associated with vascular sinus walls and probably belong to the family of
      vascular smooth muscle cells.

PMID- 18729798
TI  - Biomechanics and mechanobiology in osteochondral tissues.
AB  - Osteochondral tissues are those that form the synovial joints, namely cartilage
      and bone, including sub-chondral bone. The biomechanical purpose of synovial
      joints is to provide lubricated contact between the moving surfaces with as
      little frictional forces as possible. This is achieved by separating the
      cartilage layers by a thin film of fluid and supporting the cartilage layers by a
      bony trabecular network that becomes dense and more calcified immediately
      underneath the cartilage layer. Each tissue's biomechanical behavior is well
      understood after several decades of research and this behavior is briefly
      reviewed here, as are the concepts relating to the mechanical induction of
      cartilage degradation (osteoarthritis) with a discussion of clinical strategies
      for repair. Focusing on tissue-engineering strategies, the following concepts are
      reviewed: scaffolds, bioreactors and computational simulations, with an analysis
      of how these elements may be combined in future.

PMID- 18729799
TI  - Catalyzing stem cell research.
AB  - In 2001, the Stem Cell Network was the first of its kind, a bold initiative to
      forge and nurture pan-Canadian collaborations involving researchers, engineers,
      clinicians and private and public sector partners. Canada's broad and deep pool
      of stem cell talent proved to be a fertile ground for such an initiative, giving
      rise to a strong, thriving network that, 7 years later, can list innovative cell
      expansion and screening technologies, early-phase clinical trials for stroke,
      pulmonary hypertension, muscular dystrophy and cornea replacement, and leading
      discourse on ethical, legal and social issues among its accomplishments. As it
      moves into its second and final phase of funding, the Stem Cell Network continues
      to push boundaries and has set its sights on overcoming the obstacles that impede
      the transfer of research findings to clinical applications, commercial products
      and public policy.

PMID- 18729800
TI  - Crossing frontiers in biomaterials and regenerative medicine. 8th World
      Biomaterials Congress, 28 May - 1 June, Amsterdam, The Netherlands.

PMID- 18729801
TI  - Advances in regenerative medicine. Advances in Regenerative Medicine, 13 June
      2008, BioPark, Hertfordshire, UK.

PMID- 18729803
TI  - Combating the Tithonus error: what works?

PMID- 18729804
TI  - Exercise-induced activation of STAT3 signaling is increased with age.
AB  - Activation of the transcription factor signal transducers and activators of
      transcription (STAT) 3 is common to many inflammatory cytokines and growth
      factors, with recent evidence of involvement in skeletal muscle regeneration. The
      purpose of this study was to determine whether STAT3 signaling activation is
      regulated differentially, at rest and following intense resistance exercise, in
      aged human skeletal muscle. Skeletal muscle biopsies were harvested from healthy
      younger (n = 11, 20.4 +/- 0.8 years) and older men (n = 10, 67.4 +/- 1.3 years)
      under resting conditions and 2 h after the completion of resistance exercise. No
      differences were evident at rest, whereas the phosphorylation of STAT3 was
      significantly increased in old (23-fold) compared to young (5-fold) subjects
      after exercise. This correlated with significantly higher induction of the STAT3
      target genes including; interleukin-6 (IL-6), JUNB, c-MYC, and suppressor of
      cytokine signaling (SOCS) 3 mRNA in older subjects following exercise. Despite
      increased SOCS3 mRNA, cellular protein abundance was suppressed. SOCS3 protein is
      an important negative regulator of STAT3 activation and cytokine signaling. Thus,
      in aged human muscle, elevated responsiveness of the STAT3 signaling pathway and
      suppressed SOCS3 protein are evident following resistance exercise. These data
      suggest that enhanced STAT3 signaling responsiveness to proinflammatory factors
      may impact on mechanisms of muscle repair and regeneration.

PMID- 18729806
TI  - Identifying the genes and genetic interrelationships underlying the impact of
      calorie restriction on maximum lifespan: an artificial intelligence-based
      approach.
AB  - Novel artificial intelligence methodologies were applied to analyze gene
      expression microarray data gathered from mice under a calorie restriction (CR)
      regimen. The data were gathered from three previously published mouse studies;
      these datasets were merged together into a single composite dataset for the
      purpose of conducting a broader-based analysis. The result was a list of genes
      that are important for the impact of CR on lifespan, not necessarily in terms of
      their individual actions but in terms of their interactions with other genes.
      Furthermore, a map of gene interrelationships was provided, suggesting which
      intergene interactions are most important for the effect of CR on life extension.
      In particular our analysis showed that the genes Mrpl12, Uqcrh, and Snip1 play
      central roles regarding the effects of CR on life extension, interacting with
      many other genes (which the analysis enumerates) in carrying out their roles.
      This is the first time that the genes Snip1 and Mrpl12 have been identified in
      the context of aging. In a follow-up analysis aimed at validating these results,
      the analytic process was rerun with a fourth dataset included, yielding largely
      comparable results. Broadly, the biological interpretation of these analytical
      results suggests that the effects of CR on life extension are due to multiple
      factors, including factors identified in prior theories of aging, such as the
      hormesis, development, cellular, and free radical theories.

PMID- 18729805
TI  - Deficiency of insulin-like growth factor 1 reduces sensitivity to aging
      associated cardiomyocyte dysfunction.
AB  - Circulating insulin-like growth factor-1 (IGF-1) levels are linked to cardiac
      performance and lifespan. However, the role of IGF-1 levels in aging-associated
      cardiac dysfunction has not been defined. This study was designed to evaluate the
      impact of severe liver IGF-1 deficiency (LID) on aging-induced cardiomyocyte
      contractile and intracellular Ca(++) dysfunction. Cardiomyocytes were isolated
      from young (2- to 4-month-old) and old (24- to 26-month-old) male C57BL/6 and LID
      mice. Cardiomyocyte contractile and intracellular Ca(++) transient properties
      were evaluated, including peak shortening (PS), maximal velocity of
      shortening/relengthening (+/-dL/dt), time-to-PS (TPS), time-to-90% relengthening
      (TR(90)), electrically stimulated change in fura-fluorescence intensity
      (DeltaFFI), and intracellular Ca(++) decay rate. Aged C57BL/6 myocytes displayed
      reduced PS, +/-dL/dt and DeltaFFI as well as prolonged TR(90) and intracellular
      Ca(++) decay. IGF-1 deficiency decreased +/-dL/dt, and prolonged TR(90) with
      little change in other mechanical indices. Interestingly, LID dampened aging
      induced changes in cardiomyocyte function. Aging and IGF-1 deficiency both
      contributed to whole-body glucose intolerance. Aging downregulated expression of
      Akt, Klotho, and pAMPK, whereas it upregulated p53 expression, the effects of
      which were cancelled by IGF-1 deficiency. Aging and IGF-1 deficiency
      significantly reduced expression of the transcriptional factor Foxo3a without an
      overt effect on the mammalian target of rapamycin (mTOR) level. Collectively,
      these data depicted that IGF-1 deficiency may reduce the cardiomyocyte
      sensitivity to aging-induced mechanical dysfunction. Our data suggest that
      regulation of Akt, p53, adenosine monophosphate-activated protein kinase (AMPK)
      phosphorylation, and Klotho may play a role, at least in part, in IGF-1
      deficiency-induced "desensitization" of cardiac aging.

PMID- 18729807
TI  - Host cell mobilization for in situ tissue regeneration.
AB  - Although small, localized injuries can be healed through the body's normal
      reparative process, large traumatic injury overwhelms this system and may result
      in a deficit of functional recovery, despite the use of conventional
      reconstructive modalities. Cell-based approaches using tissue engineering and
      regenerative medicine techniques have offered new opportunities for treatment.
      Although the fundamental principles of cell-based therapies have been
      demonstrated clinically on multiple tissue systems, usually a donor tissue biopsy
      and ex vivo cell manipulation prior to implantation in vivo are necessary. The
      goal of the present study was to investigate whether host biologic resources and
      environmental conditions could be used for in situ tissue regeneration, which may
      eliminate the need for donor cell procurement and subsequent in vitro cell
      manipulation. To address this aim, we implanted a common biomaterial into mice
      and characterized the infiltrating cells to determine their regenerative
      potential. We showed that host cell infiltrates are not entirely comprised of
      inflammatory and fibroblast-like cells and the normal inflammatory process can be
      altered by incorporating anti-inflammatory agents that influence the formation of
      scar tissue. In addition, the infiltrating cells are capable of differentiating
      into multiple cell lineages, including osteogenic, myogenic, adipogenic, and
      endothelial lineages, if appropriate conditions are provided. These results
      suggest that it is possible to recruit a predominance of cells with multilineage
      potential into a biomaterial scaffold. Therefore, it may be possible to enrich
      the infiltrate with such cell types and control their fate, provided the proper
      substrate-mediated signaling can be imparted into the scaffold for in situ tissue
      regeneration.

PMID- 18729808
TI  - Cryopreservation of whole murine and porcine livers.
AB  - Preservation of vascularized organs, such as the liver, is limited to 24 h before
      destructive processes disqualify them for transplantation. This narrow window of
      opportunity prevents the performance of optimal pathogen screening and matching
      tests and possibly results in the need for retransplantation. Numerous problems
      are associated with freezing and thawing a whole liver while preserving its
      viability upon thawing, including complicated geometry, poor heat transfer,
      release of latent heat, and the difficulty of generating a uniform cooling rate.
      On the basis of our past success with sheep ovaries, we have now applied our
      novel freezing technique to a larger solid organ, the liver. Whole rat and pig
      livers were frozen and thawed using directional solidification apparatus, and
      viability of these livers was tested by means of integrity and functionality in
      vitro and in auxiliary liver transplantation. The thawed rat and porcine livers
      were intact and demonstrated >80% viability. Histology revealed normal
      architecture. Bile production and blood flow following auxiliary transplantation
      were normal as well. Our encouraging results in applying this novel
      cryopreservation technique in rat and pig livers suggest that this method may
      enable better human organ donor-recipient matching in the future.

PMID- 18729809
TI  - Preliminary evidence that VEGF genetic variability confers susceptibility to
      frontotemporal lobar degeneration.
AB  - Frontotemporal lobar degeneration (FTLD) recognizes a strong genetic background,
      with 30-50% of cases with a positive family history. Despite several efforts to
      identify monogenic causes of the disease, no clear-cut genetic risk factors for
      sporadic FTLD are yet known. Recently, increasing evidence points to a pivotal
      role of vascular endothelial growth factor (VEGF) in the neurodegenerative
      process, suggesting functions not confined to its originally described vascular
      effects. The aim of this study was to investigate the role of VEGF as a genetic
      determinant to FTLD susceptibility. We evaluated a cohort of 274 unrelated
      Italian patients, including 161 subjects with frontotemporal dementia (FTD), 56
      with corticobasal degeneration syndrome, and 57 with progressive supranuclear
      palsy. Genotype and allele frequencies of four well-known polymorphisms located
      within the VEGF promoter (-2578C/A, -1190G/A, -1154G/A, and -634G/C) were
      calculated in patients and in 216 age-matched healthy subjects. Genetic analysis
      revealed the presence of several significant changes in terms of allele,
      genotype, and haplotype frequency distributions between patients and controls.
      Marked differences were observed when the FTD patient subgroup was compared with
      healthy subjects. Overall, these data provide evidence for the first time that
      VEGF gene variability represents a susceptibility factor for sporadic FTLD, at
      least in an Italian population. Future confirmatory studies are mandatory.

PMID- 18729810
TI  - Lysophosphatidic acid and adenylyl cyclase inhibitor increase proliferation of
      senescent human diploid fibroblasts by inhibiting adenosine monophosphate
      activated protein kinase.
AB  - This study was designed to elucidate the molecular mechanism underlying
      lysophosphatidic acid (LPA) and adenylyl cyclase inhibitor SQ22536 (ACI)-induced
      senescent human diploid fibroblast (HDF) proliferation. Because adenosine
      monophosphate (AMP)-activated protein kinase (AMPK) is known to inhibit cell
      proliferation, we examined the phosphorylation status of AMPK and p53 and the
      expression level of p21(waf1/cip1) after treating HDFs with LPA and ACI.
      Phosphorylation of AMPKalpha on threonine-172 (p-Thr172-AMPKalpha) increases its
      catalytic activity but phosphorylation on serine-485/491 (p-Ser485/491-AMPKalpha)
      reduces the accessibility of the Thr172 phosphorylation site thereby inhibiting
      its catalytic activity. LPA increased p-Ser485/491-AMPKalpha, presumably by
      activating cAMP-dependent protein kinase (PKA). However, ACI reduced p-Thr172
      AMPKalpha by inhibiting the LKB signaling. Our data demonstrated that both LPA
      and ACI inhibit the catalytic activity of AMPKalpha and p53 by differentially
      regulating phosphorylation of AMPKalpha, causing increased senescent cell
      proliferation. These findings suggest that the proliferation potential of
      senescent HDFs can be modulated through the regulation of the AMPK signaling
      pathway.

PMID- 18729812
TI  - Aging, stem cells, and mammalian target of rapamycin: a prospect of pharmacologic
      rejuvenation of aging stem cells.
AB  - What is the relationship between stem cell aging and organismal aging? Does stem
      cell aging cause organismal aging or vice versa? Will stem cell aging aggravate
      age-related diseases? And what is stem cell aging? As suggested herein,
      hyperstimulation of signal transduction pathways can render cells compensatorily
      irresponsive. And the hallmark of stem cell aging is poor responsiveness to
      activating stimuli. On the basis of the hypothesis that insensitivity to stimuli
      is in part due to hyperactivation of the target of rapamycin (TOR), this article
      suggests a means of pharmacologic rejuvenation of stem cells and wound-healing
      cells.

PMID- 18729811
TI  - Long-term effects of caloric restriction or exercise on DNA and RNA oxidation
      levels in white blood cells and urine in humans.
AB  - Excessive adiposity is associated with increased oxidative stress and accelerated
      aging. Weight loss induced by negative energy balance reduces markers of
      oxidation in experimental animals and humans. The long-term effects of weight
      loss induced by calorie restriction or increased energy expenditure induced by
      exercise on measures of oxidative stress and damage have not been studied in
      humans. The objective of the present study was to compare the effects of 20%
      caloric restriction or 20% exercise alone over 1 year on oxidative damage to DNA
      and RNA, as assessed through white blood cell and urine analyses. Eighteen men
      and women aged 50 to 60 years with a body mass index (BMI) between 23.5 to 29.9
      kg/m(2) were assigned to one of two conditions--20% CR (n = 9) or 20% EX (n = 9)-
      which was designed to produce an identical energy deficit through increased
      energy expenditure. Compared to baseline, both interventions significantly
      reduced oxidative damage to both DNA (48.5% and 49.6% reduction for the CR and EX
      groups, respectively) and RNA (35.7% and 52.1% reduction for the CR and EX
      groups, respectively) measured in white blood cells. However, urinary levels of
      DNA and RNA oxidation products did not differ from baseline values following
      either 12-month intervention program. Data from the present study provide
      evidence that negative energy balances induced through either CR or EX result in
      substantial and similar improvements in markers of DNA and RNA damage to white
      blood cells, potentially by reducing systemic oxidative stress.

PMID- 18729813
TI  - Clinical outcome and mechanism of soft tissue calcification in Werner syndrome.
AB  - Werner syndrome (WS) is an autosomal recessive progeroid disorder caused by
      mutations in RecQ DNA helicase. Ectopic soft tissue calcification is one of the
      well known symptoms in WS. However, the prevalence, clinical outcome, and
      mechanism of such calcification remain to be elucidated. The clinical features
      and mechanism of ectopic calcification were examined in seven patients with WS
      whose diagnosis were confirmed by a genomic DNA analysis. X-ray examinations
      revealed subcutaneous calcification in 35 of 41 major joints (85.3%). The
      patients complained of dermal pain at 23 joints among 35 joints (65.7%) with
      calcification. Refractory skin ulcers were found at the area of the skin
      overlaying the calcification in 16 joints (45.7%). In contrast, no pain or ulcers
      were observed in the joints without calcification. The presence of ectopic
      calcification could not be explained by a systemic hormonal abnormality. Cultured
      fibroblasts from WS patients underwent spontaneous mineralization in vitro in the
      normal phosphate condition, and overexpressed Pit-1, a transmembrane type III Na
      Pi cotransporter both at the mRNA and protein levels. Phosphonophormic acid, a
      specific inhibitor for Pit-1, inhibited mineralization in the WS fibroblasts.
      Both calcification and Pit-1 overexpression were detected in the skin of WS in
      situ. WS showed a high prevalence of ectopic calcification, which was associated
      with dermal pain and refractory skin ulcers. An overexpression of Pit-1 therefore
      seems to play a key role in the formation of soft tissue calcification in this
      syndrome.

PMID- 18729814
TI  - Carnosine [corrected] increases efficiency of DOPA therapy of Parkinson's
      disease: a pilot study.
AB  - The addition of the neuropeptide carnosine (beta-alanyl-L-histidine) as a food
      additive to the basic protocol of Parkinson's disease treatment results in
      significant improvement of neurological symptoms, along with increase in red
      blood cell Cu/Zn-SOD and decrease in blood plasma protein carbonyls and lipid
      hydroperoxides, with no noticeable change in platelets MAO B activity. The
      combination of carnosine with basic therapy may be a useful way to increase
      efficiency of PD treatment.

PMID- 18729815
TI  - Comparative value of medical diagnosis versus physical functioning in predicting
      the 6-year survival of 1951 hospitalized old patients.

PMID- 18729816
TI  - Rejuvenation Research in 2007.

PMID- 18729818
TI  - Evolvability and programmed aging: a reply to de Grey.

PMID- 18729819
TI  - Interview with Rudolf Jaenisch, M.D.

PMID- 18729820
TI  - Supercentenarians table: earliest validated supercentenarian by nation of birth.

PMID- 18729822
TI  - Molecular imaging study on in vivo distribution and pharmacokinetics of modified
      small interfering RNAs (siRNAs).
AB  - Molecular imaging was used to study the biodistribution, pharmacokinetics, and
      activity of naked small interfering RNAs (siRNAs). siRNAs with riboses chemically
      modified in the 2' position were compared with unmodified siRNA. In vitro,
      replacement of the 2'-hydroxyl (2'OH) group of certain nucleotides in an siRNA
      sequence by a fluorine atom (2'F) on both antisense (AS) and sense (S) strands
      [2'F(AS/S)], or by a methoxy group (2'OMe) on the S strand [2'OH(AS)/2'OMe(S)],
      was compatible with RNA interference. Different siRNAs [2'F(AS/S),
      2'OH(AS)/2'OMe(S), and 2'OH(AS/S)] were labeled with fluorine-18 (conjugation
      with [(18)F]FPyBrA), and comparative dynamic and quantitative imaging was
      performed with positron emission tomography. After intravenous injections of
      [(18)F]siRNAs in rodents, total radioactivity was rapidly eliminated by the
      kidneys and the liver. Tissue distribution of the different siRNAs were similar,
      and their bioavailability (as judged from blood persistence and stability)
      increased in the order 2'OH(AS/S) = 2'OH(AS)/2'OMe(S) < 2'F(AS/S). However, in
      our in vivo model, the 2'F(AS/S) siRNA, despite its higher bioavailability, was
      not able to induce a higher interference effect with respect to the 2'OH(AS/S)
      siRNA. Molecular imaging approaches, applied in the present work to both natural
      and chemically modified siRNAs, can contribute to the development of these
      macromolecules as therapeutic agents.

PMID- 18729823
TI  - Pharmacokinetic analysis of polyamide nucleic-acid-cell penetrating peptide
      conjugates targeted against HIV-1 transactivation response element.
AB  - We have demonstrated that polyamide nucleic acids complementary to the
      transactivation response (TAR) element of HIV-1 LTR inhibit HIV-1 production when
      transfected in HIV-1 infected cells. We have further shown that anti-TAR PNA
      (PNA(TAR)) conjugated with cell-penetrating peptide (CPP) is rapidly taken up by
      cells and exhibits strong antiviral and anti-HIV-1 virucidal activities. Here, we
      pharmacokinetically analyzed (125)I-labeled PNA(TAR) conjugated with two CPPs: a
      16-mer penetratin derived from antennapedia and a 13-mer Tat peptide derived from
      HIV-1 Tat. We administered the (125)I-labeled PNA(TAR)-CPP conjugates to male
      Balb/C mice through intraperitoneal or gavage routes. The naked (125)I-labeled
      PNA(TAR) was used as a control. Following a single administration of the labeled
      compounds, their distribution and retention in various organs were monitored at
      various time points. Regardless of the administration route, a significant
      accumulation of each PNA(TAR)-CPP conjugate was found in different mouse organs
      and tissues. The clearance profile of the accumulated radioactivity from
      different organs displayed a biphasic exponential pathway whereby part of the
      radioactivity cleared rapidly, but a significant portion of it was slowly
      released over a prolonged period. The kinetics of clearance of individual
      PNA(TAR)-CPP conjugates slightly varied in different organs, while the overall
      biphasic clearance pattern remained unaltered regardless of the administration
      route. Surprisingly, unconjugated naked PNA(TAR) displayed a similar distribution
      and clearance profile in most organs studied although extent of its uptake was
      lower than the PNA(TAR)-CPP conjugates.

PMID- 18729824
TI  - Accommodation of physostigmine and its analogues by acetylcholinesterase is
      dominated by hydrophobic interactions.
AB  - The role of the functional architecture of the HuAChE (human
      acetylcholinesterase) in reactivity toward the carbamates pyridostigmine,
      rivastigmine and several analogues of physostigmine, that are currently used or
      considered for use as drugs for Alzheimer's disease, was analysed using over 20
      mutants of residues that constitute the interaction subsites in the active
      centre. Both steps of the HuAChE carbamylation reaction, formation of the
      Michaelis complex as well as the nucleophilic process, are sensitive to
      accommodation of the ligand by the enzyme. For certain carbamate/HuAChE
      combinations, the mode of inhibition shifted from a covalent to a noncovalent
      type, according to the balance between dissociation and covalent reaction rates.
      Whereas the charged moieties of pyridostigmine and rivastigmine contribute
      significantly to the stability of the corresponding HuAChE complexes, no such
      effect was observed for physostigmine and its analogues, phenserine and
      cymserine. Moreover, physostigmine-like ligands carrying oxygen instead of
      nitrogen at position -1 of the tricyclic moiety (physovenine and
      tetrahydrofurobenzofuran analogues) displayed comparable structure-function
      characteristics toward the various HuAChE enzymes. The essential role of the
      HuAChE hydrophobic pocket, comprising mostly residues Trp(86) and Tyr(337), in
      accommodating (-)-physostigmine and in conferring approximately 300-fold
      stereoselectivity toward physostigmines, was elucidated through examination of
      the reactivity of selected HuAChE mutations toward enantiomeric pairs of
      different physostigmine analogues. The present study demonstrates that certain
      charged and uncharged ligands, like analogues of physostigmine and physovenine,
      seem to be accommodated by the enzyme mostly through hydrophobic interactions.

PMID- 18729825
TI  - The mechanism of specific binding of free cholesterol by the steroidogenic acute
      regulatory protein: evidence for a role of the C-terminal alpha-helix in the
      gating of the binding site.
AB  - Steroidogenesis depends on the delivery of free cholesterol to the inner
      mitochondrial membrane by StAR (steroidogenic acute regulatory protein).
      Mutations in the StAR gene leads to proteins with limited cholesterol-binding
      capacity. This gives rise to the accumulation of cytoplasmic cholesterol, a
      deficit in steroid hormone production and to the medical condition of lipoid
      congenital adrenal hyperplasia. A detailed understanding of the mechanism of the
      specific binding of free cholesterol by StAR would be a critical asset in
      understanding the molecular origin of this disease. Previous studies have led to
      the proposal that the C-terminal alpha-helix 4 of StAR was undergoing a
      folding/unfolding transition. This transition is thought to gate the cholesterol
      binding site. Moreover, a conserved salt bridge (Glu169-Arg188) in the
      cholesterol-binding site is also proposed to be critical to the binding process.
      Interestingly, some of the documented clinical mutations occur at this salt
      bridge (E169G, E169K and R188C) and in the C-terminal alpha-helix 4 (L275P). In
      the present study, using rationalized mutagenesis, activity assays, CD,
      thermodynamic studies and molecular modelling, we characterized the alpha-helix 4
      mutations L271N and L275P, as well as the salt bridge double mutant E169M/R188M.
      The results provide experimental validation for the gating mechanism of the
      cholesterol-binding site by the C-terminal alpha-helix and the importance of the
      salt bridge in the binding mechanism. Altogether, our results offer a molecular
      framework for understanding the impact of clinical mutations on the reduction of
      the binding affinity of StAR for free cholesterol.

PMID- 18729827
TI  - Disruption of a mitochondrial RNA-binding protein gene results in decreased
      cytochrome b expression and a marked reduction in ubiquinol-cytochrome c
      reductase activity in mouse heart mitochondria.
AB  - Mice homozygous for a defect in the PTCD2 (pentatricopeptide repeat domain
      protein 2) gene were generated in order to study the role of this protein in
      mitochondrial RNA metabolism. These mice displayed specific but variable
      reduction of ubiquinol-cytochrome c reductase complex activity in mitochondria of
      heart, liver and skeletal muscle due to a decrease in the expression of
      mitochondrial DNA-encoded cytochrome b, the catalytic core of the complex. This
      reduction in mitochondrial function has a profound effect on the myocardium, with
      replacement of ventricular cardiomyocytes by fibro-fatty tissue. Northern
      blotting showed a reduction in the mRNA for the mitochondrial DNA encoded
      proteins cytochrome b (cytb) and ND5 (NADH dehydrogenase subunit 5) and an
      elevation in a combined pre-processed ND5-CYTB transcript. This suggests that the
      PTCD2 protein is involved in processing RNA transcripts involving cytochrome b
      derived from mitochondrial DNA. This defines the site for PTCD2 action in
      mammalian mitochondria and suggests a possible role for dysfunction of this
      protein in the aetiology of heart failure.

PMID- 18729829
TI  - [The use of real time three-dimensional echocardiography in clinical practice].

PMID- 18729826
TI  - beta-Arrestin1 interacts with the G-protein subunits beta1gamma2 and promotes
      beta1gamma2-dependent Akt signalling for NF-kappaB activation.
AB  - beta-Arrestins are known to regulate G-protein signalling through interactions
      with their downstream effectors. In the present study, we report that beta
      arrestin1 associates with the G-protein beta1gamma2 subunits in transfected
      cells, and purified beta-arrestin1 interacts with G(beta1gamma2) derived from in
      vitro translation. Deletion mutagenesis of beta-arrestin1 led to the
      identification of a region, comprising amino acids 181-280, as being responsible
      for its interaction with G(beta1gamma2). Overexpression of beta-arrestin1
      facilitates G(beta1gamma2)-mediated Akt phosphorylation, and inhibition of
      endogenous beta-arrestin1 expression by siRNA (small interfering RNA) diminishes
      this effect. Through investigation of NF-kappaB (nuclear factor kappaB), a
      transcription factor regulated by Akt signalling, we have found that
      overexpression of beta-arrestin1 significantly enhances G(beta1gamma2)-mediated
      nuclear translocation of NF-kappaB proteins and expression of a NF-kappaB
      directed luciferase reporter. Overexpression of beta-arrestin1 also promotes
      bradykinin-induced, G(betagamma)-mediated NF-kappaB luciferase-reporter
      expression, which is reverted by silencing the endogenous beta-arrestin1 with a
      specific siRNA. These results identify novel functions of beta-arrestin1 in
      binding to the beta1gamma2 subunits of heterotrimeric G-proteins and promoting
      G(betagamma)-mediated Akt signalling for NF-kappaB activation.

PMID- 18729828
TI  - Depletion of nucleophosmin leads to distortion of nucleolar and nuclear
      structures in HeLa cells.
AB  - NPM (nucleophosmin; also known as B23) is an abundantly and ubiquitously
      expressed multifunctional nucleolar phosphoprotein, which is involved in numerous
      cellular processes, including ribosome biogenesis, protein chaperoning and
      centrosome duplication; however, the role of NPM in the cell cycle still remains
      unknown. In the present study, we show dynamic localization of NPM throughout the
      cell cycle of HeLa cells. Using a combination of RNAi (RNA interference) and
      three-dimensional microscopy we show that NPM is localized at the chromosome
      periphery during mitosis. We also demonstrate that depletion of NPM causes
      distortion of nucleolar structure as expected and leads to unexpected dramatic
      changes in nuclear morphology with multiple micronuclei formation. The defect in
      nuclear shape of NPM-depleted cells, which is clearly observed by live-cell
      imaging, is due to the distortion of cytoskeletal (alpha-tubulin and beta-actin)
      structure, resulting from the defects in centrosomal microtubule nucleation.
      These results indicate that NPM is an essential protein not only for the
      formation of normal nucleolar structure, but also for the maintenance of regular
      nuclear shape in HeLa cells.

PMID- 18729830
TI  - [High frequency transthoracic echocardiography in diagnosis of chronic occlusions
      of major coronary arteries].
AB  - Comparative analysis of possibilities of transthoracic echocardiography (TTE) and
      coronary angiography in diagnosis of chronic occlusions of anterior descending
      (ADA), circumflex (CA), and right coronary (RA) arteries was carried out in 100
      patients (90 men, 10 women, mean age 51 +/- 11 years). With the help of TTE we
      analyzed direction, structural and temporal parameters of coronary blood flow in
      zones of potential epicardial and intramyocardial collateral filling: for ADA -
      in distal segment (dADA) and septal branches (SBADA), for CA - in obtuse marginal
      branches (OMB), for RCA - in posterior interventricular artery (PIA) and septal
      branches (SBRCA). We found that TTE was a sensitive and highly specific method of
      diagnosis of ADA and RCA occlusions, but did not allow to diagnose adequately
      occlusions of CA. We proved that main criterion of ADA occlusion was registration
      of retrograde or retroanterograde collateral blood flow in dADA or SBADA.
      Sensitivity of detection of inverted blood flow in dADA without consideration of
      direction of blood flow in SBADA in diagnosis of ADA occlusions was 77%, with
      consideration of SBRCA - 85%, specificity - 97%. Detection of retrograde or
      retroanterograde blood flow in SBADA was indicative of proximal level of artery
      lesion with sensitivity 100% and specificity 75%. Detection of retrograde or
      collateral flow in PIA or SBRCA was found to be main criterion of RCA occlusion.
      Sensitivity of detection of inverted blood flow in PIA without taking into
      account direction of blood flow in SBRCA in diagnosis of RCA occlusions was 77%,
      with consideration of SBRCA - 88%, specificity - 98%. The study of lat flow in
      SBRCA did not allow to determine accurately the level of artery lesion.

PMID- 18729831
TI  - [Objective methods of assessment of coronary angiogenesis].
AB  - Stimulatiion of coronary angiogenesis in patients with IHD appears to be one of
      perspective directions in contemporary cardiology. Therefore objective assessment
      of results with the help of instrumental methods of investigation is important.
      For assessment of the state of coronary vascular bed and myocardial perfusion in
      the clinic one can use coronarography, single photon emission computer
      tomography, positron emission tomography, magnetic resonance tomography, and
      contrast echocardiography. Novel techniques of visualization are elaborated at
      present with consideration of peculiarities of mechanisms and use of molecular
      markers of angiogenesis: visualization of integrin avb3, VEGF-receptors,
      visualization of activity of matrix metalloproteinases.

PMID- 18729832
TI  - [Experience of the use of ivabradine in clinical practice].

PMID- 18729833
TI  - [Efficacy and safety of enoxaparin use during drug-eluting stents implantation].
AB  - We assessed possibility of the use of low molecular heparin enoxaparin during
      percutaneous coronary interventions (PCI) with implantation of drug eluting
      stents. Enoxaparin was administered to 225 (0.3 mg/kg intraarterially via
      catheter) and 215 (0.5 mg/kg intravenously) patients. In comparison group (n=207)
      we used unfractionated heparin (UFG) intravenously according to standard scheme
      under control of activated clotting time. Stents implanted (n=797) were Cypher,
      Taxus, and Endeavor. Immediate angiographic success was 100%. During 48 hours
      after PCI pronounced bleeding (4.3%) and blood transfusions predominated in UFG
      treated patients. Number of bleedings was minimal after the intra-arterial use of
      enoxaparin (0.3 mg/kg). However total rate of all adverse events after PCI turned
      out to be minimal (7.0%) in the group of patients receiving enoxaparin
      intravenously (0.5 mg/kg). Thus the use of low molecular heparin enoxaparin is
      justified during implantation of drug eluting stents. Its optimal dose according
      to data obtained is 0.5 mg/kg intravenously.

PMID- 18729834
TI  - [Resistance to antiplatelet drugs in patients with non ST elevation acute
      coronary syndrome].
AB  - Rate of resistance to aspirin and clopidogrel was assessed in 44 patients with
      non ST elevation acute coronary syndrome. Platelet aggregation was studied by
      method of Born. Criterion of resistance to aspirin was arachidonic acid induced
      aggregation > or =20%. Patients with lowering of ADP induced aggregation < 10%,
      10 - 29% and 30% relative to initial level were considered resistant, partially
      resistant, and sensitive to therapy with clopidogrel, respectively. It was shown
      that rate of resistance to aspirin, clopidogrel, and both drugs reached 25.7,
      17.1, and 5.7%, respectively.

PMID- 18729835
TI  - [Clinico-economical efficacy of angiotensin converting enzyme inhibitors in
      patients with arterial hypertension and ischemic heart disease].
AB  - We conducted comparative analysis of clinico-economical efficacy of angiotensin
      converting enzyme inhibitors as components of combination therapy of patients
      with arterial hypertension and ischemic heart disease. Clinical efficacy of
      fosinopril, moexipril, perindopril, and ramipril was comparable: in compared
      groups statistically significant lowering of arterial pressure was achieved by
      day 6 of treatment and this lowering persisted up to day 36 of therapy with
      ramipril. All studied drugs were well tolerated. Ramipril was notable for highest
      economical efficacy determined by the method of ?"minimization of expenditures?".
      Technology of assessment of clinico-economical effectiveness of preparations from
      the same pharmacological group can be used in compilation of standards of drug
      therapy of various diseases, basing on which a physician administers a concrete
      drug to a concrete patient.

PMID- 18729836
TI  - [Regression of left ventricular hypertrophy and improvement of its diastolic
      function in patients with arterial hypertension under influence of
      antihypertensive therapy].
AB  - Antihypertensive therapy with sequential addition of drugs (noliprel, noliprel
      forte, metoprolol, amlodipine) for achievement of target blood pressure (BP)
      below 140/90 mm Hg was used in the treatment of 99 patients with arterial
      hypertension (AH) with (n=51) or without left ventricular (LV) hypertrophy (LVH).
      At initial Doppler study of transmitral blood flow all patient with LVH had type
      1 (n=48) or type 2 (n=3) diastolic LV dysfunction. Among patients without LVH 13
      had minor type 1 diastolic LV dysfunction. After 12 - 14 months of
      antihypertensive therapy in all 44 patients with moderate LVH (myocardial mass
      index below 140 g/m2) BP corresponded to target level. This was associated with
      6% decrease of myocardial mass index (MMI) and its normalization in 2/3 of
      patients, restoration of diastolic function in 3/4 of patients and its
      improvement in other patients, decrease of functional class, in rease of 6 min
      walking distance, and improvement of quality of life according to questionnaire
      for patients with CHF. In 7 patients with pronounced LVH (MMI 140 g/m2) target BP
      was not achieved, LVMMI, diastolic function, and functional class did not change,
      however tolerance to physical effort and quality of life improved. Thus in all
      patients with AH without LVH target BP level was achieved. In minor initial
      diastolic dysfunction diastolic function restored to normality, functional class,
      tolerance to physical work and quality of life improved.

PMID- 18729837
TI  - [Peculiarities of hemostasis, metabolic activity of platelets, and rate of
      aspirin resistance in patients with chronic heart failure after aorto-coronary
      bypass surgery].
AB  - Aim of the study was to investigate in dynamics peculiarities of hemostasis
      including platelet aggregation and activity of NADP-dependent dehydrogenases in
      platelets, as well as prevalence of resistance to aspirin in patients with
      functional class II-III chronic heart failure (CHF). We determined parameters of
      vascular thrombocytic and coagulative hemostasis, the state of intracellular
      metabolism of platelets as assessed by activity of NADP-dependent dehydrogenases
      in 46 men (age 45 - 72 years) with NYHA class II (n=16) and III (n=30) CHF before
      and in 12 - 14 days after coronary artery bypass grafting (CABG). After CABG all
      patients received aspirin (75 - 150 mg/day). Patients with ischemic CHF had
      moderate activation of intravascular coagulation, endotheliosis, elevation of
      fibrinogen and plasminogen levels. These processes were significantly augmented
      after CABG and were most pronounced in class II CHF. At the background of therapy
      with aspirin in 36 patients (78.3%) ADP and adrenaline induced platelet
      aggregation was reduced 2 - 3 times. In 10 patients (21.7%) aggregation remained
      at initial level or even increased what evidenced for resistance to aspirin.
      Among patients with functional classes II and III CHF portion of resistant to
      aspirin was 12.5 and 26.6%, respectively. In these patients most striking changes
      in intracellular metabolism of platelets were revealed. These changes manifested
      as derangements of energetic and plastic processes in the cell. Thus aspirin
      resistant patients with CHF comprise a group with risk of development of
      atherothrombosis of coronary arteries, arteriovenous grafts and arterial
      conduits.

PMID- 18729838
TI  - [Characteristics of pharmacological and toxic effects of verapamil during cardiac
      arrhythmia in thyrotoxic and hypothyroid rats].
AB  - Aim of this study was to investigate antiarrhythmic and toxic effects of
      verapamil in mice and rats with thyrotoxicosis and hypothyroidism. We found that
      changes of thyroid status lead to the increased sensitivity of animals to
      toxicity of verapamil. At single intraperitoneal introduction of verapamil, LD50
      was 118 +/- 7,7 mg/kg for control euthyroid mice, 53 +/- 4,1 mg/kg for
      hypothyroid mice, and 77 +/- 6,5 mg/kg for thyrotoxic mice. Sensitivity of rat
      myocardium to arrhythmogenic effects of calcium chloride increased with
      development of thyrotoxicosis and hypothyroidism. Effective arrhythmogenic dose
      of CaCl2 was 200 mg/kg for euthyroid rats and 140 mg/kg for rats with thyroid
      dysfunction. Intravenous introduction of verapamil had antiarrhythmic activity in
      rats with experimental thyroid dysfunction but at a lower effective dose.
      Effective preventive dose of verapamil was 3 - 4,5 mg/kg for euthyroid rats and 2
      - 2,5 mg/kg for rats with thyrotoxicosis and hypothyroidism. Effective dose of
      verapamil during rhythm disturbance was 3 mg/kg for control euthyroid rats and
      1,5 - 2 mg/kg for rats with abnormal thyroid status. These results provide a
      basis for the new individual approach for treatment of patients with cardiac
      arrhythmia combined with thyroid dysfunction.

PMID- 18729839
TI  - [Brain natriuretic peptide - contemporary marker of chronic heart failure].

PMID- 18729841
TI  - [The problem of complications of percutaneous coronary interventions. Part III.
      Optimal hemostasis].
AB  - Successes in interventional cardioangiology allowed to widen area of application
      of percutaneous interventions. After broadened anticoagulant and antiplatelet
      therapy introducers are often withdrawn several hours after procedure. As a
      consequence exended compression of puncture site is required. This results in
      increase of procedure time, rate of development of complications, as well as
      patient s discomfort. Devices elaborated for puncture site closure allow
      shortening of introducer presence in an artery, hemostasis duration, and length
      of hospitalization. However the use of these devices is associated with higher
      cost and possibility of complications related to their placement. Aim of the
      present review is comparison of various types of closure devices with each other
      and with manual compression as well as assessment of their effect on rate of
      development of peripheral complications.

PMID- 18729843
TI  - Determination of the charge of the plasma proteins and consequent Donnan
      equilibrium across the capillary barriers in the rat microvasculature.
AB  - AIM: Due to the negatively charged proteins in plasma, a Donnan equilibrium will
      be formed between plasma and interstitium or, as in the glomerulus, between
      glomerular plasma and Bowman's space. The phenomenon is of great physiological
      significance in the sense that the electro-osmotic pressure offered by the small
      ions attracted to the proteins may account for an important part of the total
      colloid osmotic pressure and also as the electric potential consequent to the
      Donnan distribution will affect the transcapillary transport of all charged
      molecular compounds. The present study aimed at estimating the protein charge in
      rat plasma in order to validate its importance for colloid osmotic pressure and
      potential. METHODS: The charge of the plasma proteins was determined in vitro
      from the concentration of sodium across a cellophane membrane separating a rat
      plasma sample from saline alone. However, in order to improve the sensitivity of
      the method, the studies were carried out at an ionic strength of 1/10 of
      physiological saline. RESULTS: The average charge of plasma was estimated at 0.23
      +/- 0.003 mEq g(-1) protein (mean +/- SE), and the standard variation at +/-0.01
      mEq g(-1), i.e. about 5%. At the normal protein concentration in Wistar rats of
      50 g L(-1), the charge of the proteins in systemic plasma was calculated to be
      11.5 mEq L(-1), whereas in glomerular and peritubular capillary plasma, the
      larger protein concentration increases the protein charge to 14.4 mEq L(-1).
      CONCLUSION: The results verify that the plasma protein charge accounts for about
      one-third of the total colloid osmotic pressure and that the obtained potential
      will constitute a major driving force for the transport of charged molecular
      compounds.

PMID- 18729844
TI  - Effect of fetal anaemia on myocardial ischaemia-reperfusion injury and coronary
      vasoreactivity in adult sheep.
AB  - AIMS: We investigated whether chronic fetal anaemia affects myocardial infarct in
      adulthood and elicits functional modifications in adult coronary vasoreactivity.
      METHODS: Seven-month-old sheep that were made anaemic in utero and transfused to
      normal haematocrit before birth were studied. Infarct size was determined by
      tetrazolium after 1-h ischaemia (occlusion of the mid of left anterior descending
      artery) and 2-h reperfusion. The dose-response to vasoconstrictors and
      vasodilators was assessed in small resistance coronary arteries. RESULTS: There
      were no significant differences between the animals previously subjected to in
      utero anaemia and the control animals regarding the percentage infarct size and
      the area-at-risk to the left ventricle. The ventricular function (dP/dt) was
      preserved. The percentage infarct size of the area-at-risk (70.7 +/- 3.5%) was
      larger than that in the controls (49.8 +/- 4.5%) (P = 0.006). The vascular
      responses were not altered. Endothelium-dependent relaxation to bradykinin (96.0
      +/- 2.6% vs. 98.8 +/- 1.0%) was not affected by PGI(2) inhibitor (94.6 +/- 2.6%
      vs. 98.5 +/- 1.0%) but significantly reduced by the inhibition of nitric oxide
      (NO) in both anaemic (P < 0.05) and control (P < 0.001) groups with a significant
      right shift of EC(50) (P < 0.01). The non-NO-non-PGI(2)-mediated relaxation was
      slightly potentiated in anaemic animals. CONCLUSIONS: Exposing fetal sheep to in
      utero anaemia in late gestation for 3 weeks may increase the susceptibility of
      adult hearts to ischaemia-reperfusion injury without major alterations in
      coronary vasomotor responsiveness. The impact of in utero anaemia at earlier
      period of pregnancy and on the earlier or later life of the adult is yet to be
      further investigated.

PMID- 18729845
TI  - A model of the long-term cost effectiveness of scheduled maintenance treatment
      with infliximab for moderate-to-severe ulcerative colitis.
AB  - BACKGROUND: Infliximab (IFX) has been shown to be efficacious in moderate-severe
      ulcerative colitis (UC). Aim To evaluate the cost-effectiveness of a scheduled
      maintenance treatment (SMT) with IFX in moderate-severe UC patients. METHODS: A
      Markov model was constructed to simulate the progression of a cohort of moderate
      severe UC patients treated with IFX (5 mg/kg) SMT. Transitions were estimated
      from two phase III trials of IFX (ACT I and ACT II). Standard care, comprising
      immunomodulators and/or corticosteroids was used as a comparator. Two separate
      treatment strategies were evaluated - continued treatment in IFX responders and
      continued treatment in IFX patients achieving remission. The dose of IFX was
      estimated for a 73 kg typical UC patient in the UK. The results were calculated
      over 10 years using a discount rate of 3.5% for costs and outcomes. The outcome
      measure was quality-adjusted life years (QALYs) estimated using EQ-5D.
      Sensitivity analyses explored the uncertainty around the results. RESULTS: The
      incremental cost effectiveness ratio (ICER) for IFX was 27,424 pounds in the
      responder strategy and 19,696 pounds in the remission strategy at 10 years. In
      sensitivity analysis, the ICER for IFX in the responder strategy ranged from
      21,066 pounds to 86,322 pounds and in the remission strategy ranged from 14,728
      pounds to 46,765 pounds. The model time horizon and patient body weight were
      important factors affecting results. CONCLUSION: Eight-week SMT with IFX appears
      to be a cost-effective treatment option for adult patients suffering from
      moderate to severe UC.

PMID- 18729846
TI  - Evaluating the process of care in nonvariceal upper gastrointestinal haemorrhage:
      a survey of expert vs. non-expert gastroenterologists.
AB  - BACKGROUND: When faced with the same facts, physicians often make different
      decisions. Aim To perform a survey to measure the process of care and variations
      in decision-making in nonvariceal upper gastrointestinal tract haemorrhage
      (NVUGIH) and compare results between experts and non-experts. METHODS: We
      administered a vignette survey to elicit knowledge and beliefs about NVUGIH,
      including 13 'best practice' guidelines. We compared guideline compliance between
      experts and non-experts. RESULTS: One hundred and eighty-eight
      gastroenterologists responded (46%). Experts endorsed more 'best practices' than
      non-experts (93% vs. 85%; P = 0.002). Non-experts were more likely to endorse
      incorrectly bolus dosing vs. continuous infusion of intravenous proton pump
      inhibitors (PPIs; 92% vs. 64%; P = 0.005) and to select standard-channel vs.
      large-channel endoscopes in high-risk bleeding (100% vs. 85%; P = 0.04). There
      were wide variations within groups regarding the timing of nasogastric lavage,
      use of promotility agents, use of hemoclips and appropriateness of snaring clots
      overlying ulcers. CONCLUSIONS: Experts are more likely to comply with NVUGIH
      guidelines. Non-experts diverge from experts in the dosing of PPIs and choice of
      endoscope in high-risk bleeding. Moreover, there are wide variations in key
      practices even within groups. This suggests that best practices have been
      generally well disseminated, but that persistent disconnects exist that should be
      further investigated.

PMID- 18729847
TI  - Systematic review: adverse event reports for oral sodium phosphate and
      polyethylene glycol.
AB  - BACKGROUND: Screening colonoscopy exposes healthy patients to the risk of serious
      adverse events associated with bowel preparation. Randomized controlled trials
      are not an effective method for evaluating this risk. AIM: To search published
      literature in order to characterize the risk of adverse events associated with
      oral polyethylene glycol (PEG) or sodium phosphate (NaP). METHODS: A systematic
      review identified case reports of any serious events associated with PEG or NaP.
      Reports to the Food and Drug Administration (FDA) were also examined. RESULTS:
      Fifty-eight publications of significant events in 109 patients using NaP and 22
      patients using PEG were identified. As the total number of prescriptions issued
      is unknown, rates for the two agents cannot be directly compared. Most commonly
      reported were electrolyte disturbances, renal failure and colonic ulceration for
      NaP and Mallory-Weiss tear, electrolyte disturbances and allergic reactions for
      PEG between January 2006 and December 2007; there were 171 cases of renal failure
      reported to the FDA following use of NaP and 10 following PEG. CONCLUSIONS:
      Adverse events following bowel preparation are uncommon, but potentially serious.
      Given that many of these patients are healthy individuals undergoing screening,
      the benefit/risk ratio must be carefully considered when deciding which
      preparation to prescribe in individual patients.

PMID- 18729848
TI  - Changing perceptions and practices regarding aspirin, nonsteroidal anti
      inflammatory drugs, and cyclooxygenase-2 selective nonsteroidal anti-inflammatory
      drugs among US primary care providers.
AB  - BACKGROUND: Our understanding of the benefits and risks of aspirin non steroidal
      anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) selective NSAIDs and
      gastro-protective agents (GPAs) continues to expand. AIM: To assess the
      perceptions and practices of US primary care physicians (PCPs) regarding the use
      of aspirin, NSAIDs, COX-2 selective NSAIDs and GPA. METHODS: A 34-question survey
      was administered to 1000 US PCPs via the internet. Questions addressed issues
      involving aspirin, NSAIDs, COX-2 selective NSAIDs, and GPAs. Around 491 of 1000
      PCPs had participated in a similar survey conducted in 2003. RESULTS: Eighty-five
      per cent of PCPs reported that >25% of their patients were taking aspirin for
      preventive reasons. Nineteen per cent performed a risk calculation when deciding
      whether to start aspirin for cardioprotection. Fifty-four per cent recommended a
      proton pump inhibitor (PPI) for a patient with a recently healed ulcer who
      required ongoing aspirin. Thirty-one per cent reported prescribing NSAIDs more
      often and 52% were more likely to recommend a GPA with an NSAID than in 2003.
      Although PCPs were less likely to recommend a COX-2 selective NSAID compared to
      2003, only 41% felt that rofecoxib increased cardiovascular risk. One-third felt
      that celecoxib and traditional NSAIDs were associated with increased cardiac
      risk. CONCLUSION: This survey identified several areas of ongoing confusion
      regarding aspirin, NSAIDs, COX-2 selective NSAIDs and GPAs, which should help
      direct future educational efforts regarding the benefits, risks and appropriate
      use of these agents.

PMID- 18729849
TI  - Diagnostic performance of serum free light chain measurement in patients
      suspected of a monoclonal B-cell disorder.
AB  - The present study aimed to determine the diagnostic performance of different
      testing strategies to diagnose malignant B-cell disorder or monoclonal gammopathy
      of unknown significance (MGUS). Sensitivity and specificity were determined in
      833 consecutive patients investigated for a monoclonal gammopathy. Serum protein
      electrophoresis (PE), serum kappa/lambda free light chain (FLC) ratio, and serum
      and urine immunofixation electrophoresis (IFE) were performed in all patients.
      Twenty-eight patients were diagnosed with a malignant plasma cell disorder, 25
      with B-cell non-Hodgkin lymphoma and 156 with MGUS. Serum PE (with follow-up IFE)
      plus FLC had a sensitivity of 82.3% and a specificity of 96.8% and missed one
      plasmacytoma and 23 patients with MGUS. Serum IFE plus urine IFE had a
      sensitivity of 92.3% and a specificity of 100% and missed two MGUS patients.
      Serum IFE plus FLC had a sensitivity of 93.8% and a specificity of 96.8% and
      missed one MGUS patient. Serum PE plus FLC had a significantly lower sensitivity
      than serum IFE plus FLC or serum IFE plus urine IFE for the diagnosis of MGUS.
      The sensitivity of serum IFE plus FLC was comparable to the sensitivity of serum
      IFE plus urine IFE. The specificity of serum IFE plus FLC, however, was lower
      than the specificity of serum IFE plus urine IFE.

PMID- 18729850
TI  - MOZ/TIF2-induced acute myeloid leukaemia in transgenic fish.
AB  - The inv(8)(p11q13) chromosomal abnormality, described in acute myeloid leukaemias
      (AML), fuses the histone acetyl-transferase (HAT) MYST3 (MOZ) gene with another
      HAT gene, NCOA2 (TIF2). We generated a transgenic zebrafish in which the
      MYST3/NCOA2 fusion gene was expressed under control of the spi1 promoter. An AML
      developed in 2 of 180 MYST3/NCOA2-EGFP-expressing embryos, 14 and 26 months after
      injection of the fusion gene in a one-cell embryo, respectively. This leukaemia
      was characterised by an extensive invasion of kidneys by myeloid blast cells.
      This model, which is the first zebrafish model of AML, demonstrates the oncogenic
      potency of MYST3/NCOA2 fusion gene.

PMID- 18729851
TI  - Purification and characterization of sideroblasts from patients with acquired and
      hereditary sideroblastic anaemia.

PMID- 18729852
TI  - Secondary non-Hodgkin lymphoma (NHL) in children and adolescents after childhood
      cancer other than NHL.
AB  - The emergence of non-Hodgkin lymphoma (NHL) during childhood and adolescence as a
      secondary neoplasm (SN) after previous cancer other than NHL is rare. To describe
      the characteristics and outcome of NHL following previous cancer other than NHL
      in children and adolescents, this study analysed the data of patients reported to
      the NHL-Berlin-Frankfurt-Munster study centre from 1986 to 2005. Out of the total
      of 2968 NHL-patients registered, 11 patients were assessed as having suffered
      from NHL as a proven SN. Four additional children had most likely suffered from
      NHL as an SN, but a late relapse of the first neoplasm could not be ruled out
      unequivocally. In the patients with proven SN, median age at diagnosis of the
      primary malignancy was 3.9 years (range 2-11.7). The median age at diagnosis of
      NHL was 7.6 years (range 4.7-18). Only lymphoblastic (n = 7) and diffuse large B
      cell (n = 4) lymphomas were diagnosed as SN. The estimated 5-year event-free
      survival from time of diagnosis of NHL was 91% [95% confidence interval (CI) 74
      100%] in patients with proven SNs and 84% (95% CI 63-100%) when the patients with
      probable SNs were included in the analysis. We concluded that secondary NHL in
      children and adolescents confers a favourable prognosis.

PMID- 18729854
TI  - Association between wind speed and the occurrence of sickle cell acute painful
      episodes: results of a case-crossover study.
AB  - The role of the weather as a trigger of sickle cell acute painful episodes has
      long been debated. To more accurately describe the role of the weather as a
      trigger of painful events, we conducted a case-crossover study of the association
      between local weather conditions and the occurrence of painful episodes. From the
      Cooperative Study of Sickle Cell Disease, we identified 813 patients with sickle
      cell anaemia who had 3570 acute painful episodes. We found an association between
      wind speed and the onset of pain, specifically wind speed during the 24-h period
      preceding the onset of pain. Analysing wind speed as a categorical trait, showed
      a 13% increase (95% confidence interval: 3%, 24%) in odds of pain, when comparing
      the high wind speed to lower wind speed (P = 0.007). In addition, the association
      between wind speed and painful episodes was found to be stronger among men,
      particularly those in the warmer climate regions of the United States. These
      results are in agreement with another study that found an association between
      wind speed and hospital visits for pain in the United Kingdom, and lends support
      to physiological and clinical studies that have suggested that skin cooling is
      associated with sickle vasoocclusion and perhaps pain.

PMID- 18729853
TI  - Prevalence of familial malignancy in a prospectively screened cohort of patients
      with lymphoproliferative disorders.
AB  - Increasing evidence points to a heritable contribution in the development of
      lymphoma. The goal of this study was to determine the rate of familial
      lymphoproliferative malignancy among consecutive lymphoma patients presenting to
      a tertiary care center and to enroll families with multiple affected first-degree
      relatives on a data and tissue collection study. Beginning in 2004 all new
      patients presenting to the Dana-Farber Cancer Institute with non-Hodgkin (NHL) or
      Hodgkin lymphoma (HL) or chronic lymphocytic leukaemia (CLL) were asked to
      complete a one-page self-administered family history questionnaire. 55.4% of 1948
      evaluable patients reported a first-degree relative with a malignancy, with the
      highest rate among CLL probands. Lymphoid malignancies were particularly common,
      with 9.4% of all probands reporting a first-degree relative with a related
      lymphoproliferative disorder (LPD). This frequency was again highest for CLL, at
      13.3% of CLL probands, compared to 8.8% of NHL probands and 5.9% of HL probands
      (P = 0.002). The prevalence of CLL was significantly increased in parents of CLL
      probands (P < 0.05), and a greater risk of NHL was seen in fathers of NHL
      probands than in mothers (P = 0.026). We conclude that familial aggregation of
      LPDs is common among newly diagnosed patients, varies significantly by diagnosis
      and contributes meaningfully to the population disease burden.

PMID- 18729855
TI  - Peripheral T-cell lymphoma with a follicular growth pattern: derivation from
      follicular helper T cells and relationship to angioimmunoblastic T-cell lymphoma.

PMID- 18729856
TI  - Practical blood dendritic cell vaccination for immunotherapy of multiple myeloma.
AB  - Therapeutic vaccination combined with new drugs may cure multiple myeloma (MM).
      We have developed a bio-process to purify CMRF-56 monoclonal antibody (mAb) and a
      standard operating procedure to immunoselect blood dendritic cells (BDC).
      Leucopheresed mononuclear cells were cultured overnight, labelled with CMRF-56
      mAb and BDC prepared using a clinical scale immunoselection system. The mean BDC
      yield from healthy donors was 48% (n = 6, purity 28%). Preparations from MM
      patients (n = 6, yield 47%, purity 35%) primed cytotoxic T lymphocytes (CTL) to
      clinically relevant MM antigens. This procedure can be performed readily by
      clinical cell manufacturing units to facilitate BDC vaccination studies.

PMID- 18729857
TI  - The subcellular Sox11 distribution pattern identifies subsets of mantle cell
      lymphoma: correlation to overall survival.
AB  - Gene expression analysis demonstrated high expression of the neuronal
      transcription factor SOX11 in mantle cell lymphoma (MCL). In contrast to
      follicular lymphoma, small lymphocytic lymphoma and reactive lymphoid tissue,
      most MCLs tested (48/53 patients) expressed sox11 protein in the nucleus.
      Therefore nuclear sox11 expression represents a new tumour marker for a subset of
      MCL. However, 5/53 MCL cases expressed sox11 only in the cytoplasm; these MCL
      patients had a shorter survival compared to MCL with nuclear sox11 expression.
      These results suggest sox11 expression as a new diagnostic marker in MCL that
      could be related to the clinical and biological behaviour of MCL.

PMID- 18729858
TI  - Sulfonamide-Resistant Meningococci.

PMID- 18729859
TI  - C.M.A.'s Audio-Digest-A Decade of Progress.

PMID- 18729860
TI  - Kerr-Mills in California-Testimony Before the California Senate Fact Finding
      Committee on Labor and Welfare.

PMID- 18729861
TI  - PUBLIC HEALTH REPORT.

PMID- 18729862
TI  - Kerr-Mills Administration in California.

PMID- 18729863
TI  - Government Programs in California for the Disabled: A Report of the Bureau of
      Research and Planning, California Medical Association.

PMID- 18729864
TI  - Hospital and Insurance Coverage for the Elderly: A Study at Long Beach Community
      Hospital for Patients Over the Age of 60.

PMID- 18729866
TI  - Malcolm H. Merrill, M.D.

PMID- 18729865
TI  - WOMAN'S AUXILIARY: FOCUS-HEALTH CAREERS.

PMID- 18729867
TI  - An Exciting Scientific Program.

PMID- 18729868
TI  - The Press-Neither Friend nor Enemy.

PMID- 18729869
TI  - Health Care for the Aged-Summary of Testimony of the California Medical
      Association.

PMID- 18729870
TI  - PUBLIC HEALTH REPORT.

PMID- 18729871
TI  - Mental Illness and Private Medicine.

PMID- 18729873
TI  - CPS-A Silver Anniversary.

PMID- 18729872
TI  - Physician and Hospital.

PMID- 18729875
TI  - Continuing Consent to Treatment, Committee on Occupational Health: Informational
      Supplement.

PMID- 18729874
TI  - Dean Bostick.

PMID- 18729876
TI  - WOMAN'S AUXILIARY: International Health Activities.

PMID- 18729877
TI  - Provisions of Group Health Insurance Policies Issued in 1962: A Report of the
      Bureau of Research and Planning, California Medical Association.

PMID- 18729878
TI  - Another Annual Session.

PMID- 18729880
TI  - In Memoriam.

PMID- 18729879
TI  - Ralph C. Teall, M.D. CMA President-Elect.

PMID- 18729881
TI  - Clinical Laboratories-Statement by the CMA Commission on Community Health
      Services.

PMID- 18729883
TI  - Voluntary Health Insurance Coverage in California, 1962: A Report of the Bureau
      of Research and Planning, California Medical Association.

PMID- 18729882
TI  - PUBLIC HEALTH REPORT.

PMID- 18729885
TI  - PRESIDENT'S PAGE.

PMID- 18729884
TI  - Health Care for the Aged.

PMID- 18729886
TI  - In Memoriam.

PMID- 18729888
TI  - Guiding Principles for Physician-Hospital Relations.

PMID- 18729887
TI  - PUBLIC HEALTH REPORT.

PMID- 18729889
TI  - The Role of the Medical Staff Hospital Utilization Committee.

PMID- 18729890
TI  - Health, Insurance, and Pension Plans for Office and Plant Workers in the West,
      and in the U.S: A Report of the Bureau of Research and Planning, California
      Medical Association.

PMID- 18729892
TI  - Transactions of the House of Delegates, Los Angeles, March 21-25, 1964.

PMID- 18729891
TI  - Welcome to San Francisco.

PMID- 18729893
TI  - Proposed Constitutional Amendments for Action in 1965.

PMID- 18729894
TI  - The Role of Medicine in Society: A Progress Report of a Committee of the
      California Medical Education and Research Foundation.

PMID- 18729895
TI  - In Memoriam.

PMID- 18729896
TI  - PUBLIC HEALTH REPORT.

PMID- 18729897
TI  - Mental Illness and Private Medicine.

PMID- 18729899
TI  - AMA Meeting Results.

PMID- 18729898
TI  - Toxic Reactions To Psychopharmaceuticals.

PMID- 18729900
TI  - New Habiliment.

PMID- 18729902
TI  - California Physician Fee Index.

PMID- 18729901
TI  - A Unique Partnership.

PMID- 18729903
TI  - Public Health Report.

PMID- 18729904
TI  - The Early Cancer Cytopathology and the "Nothing Lesion".

PMID- 18729905
TI  - Woman's Auxiliary: Accentuation.

PMID- 18729907
TI  - Woman's Auxiliary.

PMID- 18729906
TI  - A New Dean At USC.

PMID- 18729909
TI  - Nurse Services in Noise Control Programs.

PMID- 18729908
TI  - AMA Positions on Discrimination and Smoking.

PMID- 18729910
TI  - Public Health Report.

PMID- 18729911
TI  - California Needs More Trained Nurses.

PMID- 18729912
TI  - Public Health Report.

PMID- 18729914
TI  - Data on Consumer Expenditures, Los Angeles and San Francisco, 1960.

PMID- 18729913
TI  - Woman's Auxiliary: Help!

PMID- 18729916
TI  - Honor for Health Director.

PMID- 18729915
TI  - Relative Value Studies-1964.

PMID- 18729917
TI  - Your Medical Assistant-A ;Girl Friday'-Plus.

PMID- 18729918
TI  - Public Health Report.

PMID- 18729919
TI  - Erythroblastosis Recommendations Misinterpreted.

PMID- 18729920
TI  - Woman's Auxiliary.

PMID- 18729921
TI  - A Successful Conference on Continuing Medical Education.

PMID- 18729923
TI  - Proposed Constitutional Amendments for Action in 1965.

PMID- 18729922
TI  - Your Scientific Board-A Beacon to Better Medicine.

PMID- 18729924
TI  - Public Health Report.

PMID- 18729925
TI  - 1965 Annual Session.

PMID- 18729926
TI  - The Blue Shield Concept.

PMID- 18729927
TI  - The Cost of Words.

PMID- 18729928
TI  - Proposed Constitutional Amendments for Action in 1965.

PMID- 18729929
TI  - Public Health Report.

PMID- 18729930
TI  - The California Medical Education and Research Foundation Its Role on Behalf of
      the Community.

PMID- 18729931
TI  - The Fetus and Its Environment.

PMID- 18729933
TI  - Halothane (Fluothane(R)) A REPORT OF THE COMMITTEE ON SCIENTIFIC INFORMATION.

PMID- 18729932
TI  - Warning-Tetracycline and Pregnancy A REPORT OF THE [ill] CHILD CARE.

PMID- 18729934
TI  - CMA Plan for Health Care for the Aged.

PMID- 18729935
TI  - The Physician and Informed Consent.

PMID- 18729936
TI  - Public Health Report.

PMID- 18729937
TI  - Woman's Auxiliary: International Health Activities.

PMID- 18729938
TI  - The Outbreak of Meningitis.

PMID- 18729939
TI  - The Physician and the Community.

PMID- 18729940
TI  - Public Health Report.

PMID- 18729941
TI  - James C. MacLaggan, M.D. CMA President-Elect.

PMID- 18729942
TI  - Public Health Report.

PMID- 18729943
TI  - Woman's Auxiliary: Husband-Wife Membership.

PMID- 18729945
TI  - Public Health Report.

PMID- 18729944
TI  - Virology 1965 et al.

PMID- 18729946
TI  - Woman's Auxiliary: Seek to Serve.

PMID- 18729947
TI  - Medical Discipline.

PMID- 18729948
TI  - President's Page.

PMID- 18729949
TI  - Actions of the House of Delegates, San Francisco, March 27 to 31, 1965.

PMID- 18729950
TI  - Proposed Constitutional Amendment and Bylaw Amendment for Action in 1966.

PMID- 18729951
TI  - Public Health Report.

PMID- 18729952
TI  - Woman's Auxiliary.

PMID- 18729953
TI  - Medicare 1965.

PMID- 18729954
TI  - New Dean at Stanford.

PMID- 18729955
TI  - A Better Journal.

PMID- 18729956
TI  - Are You Keeping Up-to-Date?

PMID- 18729957
TI  - CMERF-How You Can Support It.

PMID- 18729958
TI  - Quality of Care.

PMID- 18729959
TI  - Woman's Auxiliary: Rx: A Program.

PMID- 18729960
TI  - Another Legislative Year.

PMID- 18729961
TI  - State Fee Schedules-Report of the CMA Ad Hoc Committee.

PMID- 18729963
TI  - Community Organization to Help the Handicapped-A Guide.

PMID- 18729962
TI  - Public Health Report.

PMID- 18729964
TI  - Dr. Merrill's Departure.

PMID- 18729966
TI  - Woman's Auxiliary: Community Service.

PMID- 18729965
TI  - Public Health Report.

PMID- 18729967
TI  - Preparation for Medicare-AMA Report from Washington.

PMID- 18729968
TI  - Look for This Emblem (Medic Alert).

PMID- 18729969
TI  - CMA Acts on "Medicare".
AB  - The council of the California Medical Association at its meeting August 7, 1965,
      took two important steps bearing on Public Law 89-97, generally known as the
      "Medicare Law." One was a statement of policy and the other was creation of a
      Task Force to represent the CMA's position in whatever actions are taken in the
      state government of California or in the Federal Government to carry out the
      provisions of the new legislation.

PMID- 18729970
TI  - Public Health Report.

PMID- 18729971
TI  - Medicare in 1966.

PMID- 18729973
TI  - Dr. Fenlon Goes to Washington.

PMID- 18729972
TI  - Need for Continuous Poliomyelitis Immunization.

PMID- 18729974
TI  - AMA Actions at Special Session.

PMID- 18729976
TI  - Continuing Medical Education: The Challenging Paradox of Rapid Medical Progress.

PMID- 18729975
TI  - A Psychiatric Service for Adolescents.

PMID- 18729977
TI  - Public Health Report.

PMID- 18729979
TI  - White House Conference on Health.

PMID- 18729978
TI  - Woman's Auxiliary: It Can Happen Here.

PMID- 18729980
TI  - Automobile Injury Epidemic: The Failure of Preventive Medicine.

PMID- 18729981
TI  - A Farewell to John Hunton.

PMID- 18729982
TI  - White House Conference on Health.

PMID- 18729983
TI  - Patterns in Hospital Use-Partial Results of a Study in Massachusetts-Report of
      the Bureau of Research and Planning.

PMID- 18729984
TI  - Continuing Medical Education: A Proposal.

PMID- 18729985
TI  - EDWARD NORTON EWER, M.D.

PMID- 18729986
TI  - Woman's Auxiliary: Communication-A Necessity.

PMID- 18729987
TI  - The casey bill.

PMID- 18729989
TI  - 1965 constitutional amendments for action in 1966.

PMID- 18729988
TI  - California's New Director of Public Health.

PMID- 18729991
TI  - Utilization review plan.

PMID- 18729990
TI  - Woman's Auxiliary: Ama-Erf.

PMID- 18729993
TI  - Continuing medical education: medical radio conferences.

PMID- 18729992
TI  - A new feature.

PMID- 18729994
TI  - Woman's Auxiliary: International Health Activities.

PMID- 18729995
TI  - Professional problems in federalized health care abroad-report of the bureau of
      research and planning.

PMID- 18729996
TI  - An important meeting in prospect.

PMID- 18729997
TI  - Quick tracheotomy.

PMID- 18729998
TI  - Woman's Auxiliary: What Is WA-SAMA?

PMID- 18729999
TI  - An Important New Job For CPS.

PMID- 18730001
TI  - John G. Morrison, M.D.-CMA President-Elect.

PMID- 18730000
TI  - To all my patients.

PMID- 18730002
TI  - Woman's Auxiliary: A Word at Departure.

PMID- 18730004
TI  - Annual session, 1966.

PMID- 18730003
TI  - On "pollen and mold spores-an atmospheric and field survey".

PMID- 18730006
TI  - Proposed constitutional and bylaw amendments for action in 1967.

PMID- 18730005
TI  - Actions of the house of delegates.

PMID- 18730007
TI  - Reference committee recommendations.

PMID- 18730008
TI  - Public health report.

PMID- 18730009
TI  - Group psychotherapy with adolescents.
AB  - In working in a large general hospital with groups of disturbed adolescent
      patients from economically and emotionally deprived walks of life, therapists
      worked out a plan of outpatient group therapy that in general has had good
      results as measured by effective living and functioning in school, at home and
      with peers. Groups were limited to eight patients and meetings were held once a
      week with two co-therapists of different sexes. Therapists usually did not try to
      turn discussions in one direction or another. More active than in usual group
      work, the therapists did not hesitate to be didactic or educational as the topic
      or problem indicated.At termination of the group sessions, usually at the end of
      a school year as a natural time of leave-taking, the members who had benefited
      sufficiently faced the departure with little emotional wrench; those who had not
      were resentful, anxious, disappointed or relieved.

PMID- 18730010
TI  - Mandatory tests for phenylketonuria.

PMID- 18730011
TI  - The deceptive Acid phosphatases.

PMID- 18730012
TI  - Woman's Auxiliary: Membership Objectives.

PMID- 18730013
TI  - County teaching hospitals-a statement of the council of the california medical
      association.

PMID- 18730015
TI  - Notices and Reports: Wilbur Reelected AMA Trustee.

PMID- 18730014
TI  - Hemolytic disease of the newborn.

PMID- 18730016
TI  - Woman's Auxiliary: Keeping Pace.

PMID- 18730017
TI  - WMA Declaration of Helsinki Serves as Guide to Physicians.

PMID- 18730018
TI  - Anesthetic and recovery room records.
AB  - Anesthetic and recovery room records are important medical documents. In the past
      they have not been given adequate attention by many anesthesiologists or by most
      surgeons and other physicians involved in patient care. Anesthetic and recovery
      room records should be better prepared and better used, for they are an important
      part of the description of a surgical patient's medical experience.

PMID- 18730019
TI  - Dermatologic therapy-point and counterpoint.

PMID- 18730020
TI  - The latex serologic test for syphilis-a new screening procedure.
AB  - A new macroscopic screening test for syphilis, the Latex-sts test, is
      extraordinarily simple. After inactivation of the patient's serum for 30 minutes
      at 56 degrees C the test is performed by mixing the patient's serum with latex
      particles coated with cardiolipin and a protein fraction obtained from the non
      pathogenic Reiter strain of Treponema pallidum. Two to three minutes after
      mixing, the result of the test is observed on a ringed serologic plate. The
      sensitivity, specificity and reproducibility of the new test are equivalent to
      those of the qualitative Venereal Disease Research Laboratory tube test. The
      advantages of the Latex-sts are that it can be done in a short time, it is simple
      and it requires a minimum of laboratory equipment. The coated latex particles are
      stable for 12 months.

PMID- 18730021
TI  - Electrical cardioversion-effectiveness of quinidine prophylaxis following
      countershock.
AB  - Direct current countershock was given to 46 patients with chronic atrial
      fibrillation of diverse causes, with successful conversion in 87 per cent of
      them. Patients were observed while receiving quinidine prophylaxis, with serial
      determination of serum quinidine levels, for up to 22 months. Two quinidine
      preparations were employed, one a long-acting form, in various dosage regimens
      and both preparations were found to be effective prophylactic agents for
      maintaining reliable serum quinidine levels. Fifty per cent of patients remained
      in normal sinus rhythm at three months, 28 per cent at six months and 13 per cent
      at twelve months.

PMID- 18730022
TI  - Topical cryotherapy-use for relief of pain and spasticity.
AB  - Cold applications are sometimes of pronounced symptomatic benefit in some
      rheumatic disorders such as acute myalgia; in the temporary relief of spasticity;
      in helping to release tight structures in poliomyelitis and allied diseases; and
      in temporary recovery of energy in multiple sclerosis.

PMID- 18730023
TI  - Primary lung cancer.

PMID- 18730024
TI  - Traffic accidents-chronic medical conditions as a cause.
AB  - From comparatively scanty information, an increased traffic accident risk appears
      to be associated with several chronic medical conditions including alcoholism,
      cardiovascular disease, epilepsy, diabetes and mental illness. Further study
      probably will show that medical handicaps other than alcoholism are a factor in
      from 5 to 10 per cent of traffic accidents. However, in about half of the
      accidents caused by heart attacks, the individual has no previous knowledge of
      his illness, and prevention of the accident would not be possible. A selective
      program for identifying high risk drivers with medical conditions is feasible and
      warranted, but a program of mass medical examinations for all drivers is not.A
      very strong relationship has been shown between drunk driving and traffic
      accidents, and 50 to 75 per cent of all severe and fatal traffic accidents
      involve the use of alcohol. However, studies have shown that drivers with
      alcoholism rather than social drinkers represent the preponderance, but not the
      entirety, of those who get into trouble. A major reduction in the traffic
      accident toll may thus depend on the early identification and treatment of
      alcoholism.

PMID- 18730025
TI  - Protein-losing gastroenteropathy.
AB  - In the past 10 years with the development of improved methods, particularly
      radioisotope techniques, it has been demonstrated that a number of patients with
      gastrointestinal disease and depletion of plasma proteins become hypoproteinemic
      because of actual leakage of albumin and other plasma proteins into the lumen of
      the gastrointestinal tract. The site of protein leakage is variable depending on
      the underlying pathological state but the loss of protein-containing lymph
      through the gastrointestinal lymphatic channels seems to be the major mechanism
      for hypoproteinemia.It has become apparent that there exists a normal mechanism
      for secretion of plasma proteins into the gastrointestinal tract as part of the
      overall metabolism of the plasma proteins. When the process is exaggerated so
      that resynthesis of plasma protein cannot keep pace with its degradation,
      sometimes severe hypoproteinemia is the result. Such a pathological process has
      now been described in approximately 40 disease states. A review of all the
      techniques which can demonstrate gastroenteric protein loss reveals that there
      are no widely available quantitative tests but that accurate quantitation is not
      necessary for the diagnosis of protein losing gastroenteropathy.

PMID- 18730026
TI  - Pneumococcal pericarditis in an eight-month-old child.

PMID- 18730027
TI  - Cystic pulmonary metastasis complicating angiosarcoma of the scalp.

PMID- 18730028
TI  - Progressive pulmonary insufficiency due to mineral oil.

PMID- 18730029
TI  - Intraperitoneal migration of a Kirschner wire-report of a case.

PMID- 18730030
TI  - The rubella nightmare.

PMID- 18730031
TI  - Continuing medical education: television-the newest medium for continuing
      education in medicine.

PMID- 18730033
TI  - Woman's Auxiliary: International Health Activities.

PMID- 18730032
TI  - Public health report.

PMID- 18730034
TI  - An outside look at medical education.

PMID- 18730036
TI  - Public health report.

PMID- 18730035
TI  - Proposed constitutional amendments for action in 1967.

PMID- 18730037
TI  - Woman's Auxiliary.

PMID- 18730038
TI  - Phenylketonuria-the guthrie screening test-a method of quantitation, observations
      on reliability and suggestions for improvement.
AB  - The Guthrie bacterial inhibition assay method of screening neonatal infants for
      phenylketonuria (pku) initiated mass screening for inborn errors of metabolism.
      It is a simple, cheap procedure admirably suited to private local use as against
      private or public central use. However, using parallel fluorometric
      determinations as a basis for comparison, and 4 mg per 100 ml serum phenylalanine
      as a presumptive positive threshhold, the Guthrie test yielded 53 per cent "false
      negatives." Extrapolating from a combination of our data and reported
      phenylalanine levels at three days of age or less in proved pku patients, it is
      estimated the Guthrie test might fail to detect one of 25 pku patients screened
      at three days of age or less. Means to diminish this risk are considered.

PMID- 18730039
TI  - Bovine bile derivative treatment for cancer-a critical evaluation.
AB  - Bovine bile derivative, a material reported to be effective in cancer
      chemotherapy, was administered to 31 patients with malignant disease. In 22 cases
      the results were considered evaluable. In one of the 22 there was a suggestion of
      antitumor response. In almost all patients diarrhea and phlebitis developed and
      in 11 these complications necessitated cessation of therapy.

PMID- 18730040
TI  - Health manpower and medical associations.

PMID- 18730041
TI  - L. Henry garland, m.d.

PMID- 18730042
TI  - Continuing medical education for the practicing physician.

PMID- 18730043
TI  - Whither continuing medical education.

PMID- 18730044
TI  - The role of external irradiation in the treatment of transitional cell carcinoma
      of the bladder-a review of fifty cases.
AB  - Of 100 patients with carcinoma of the bladder seen in the Section of Therapeutic
      Radiology, University of California, San Francisco, between 1957 and 1962, 59
      were accepted for radiation treatment. Fifty had transitional cell carcinoma and
      were treated with supervolt therapy (1 mev or cobalt-60).TWO TYPES OF TUMORS WERE
      AGAIN FOUND SUITABLE FOR EXTERNAL IRRADIATION: Papillary carcinomas Grades II and
      III, as long as they have not, or at least have not massively, invaded muscle;
      and undifferentiated carcinomas, Grade IV, regardless of degree of extension
      through the pelvis. The former type, if single, is treated by irradiation for the
      first recurrence after one attempt with radical transurethral resection. In the
      presence of multiple lesions at the first examination, radiation therapy is given
      immediately. The latter type is treated by radiation therapy without any attempt
      at surgical removal.Of 37 patients, Stages A to C, treated more than three years
      ago, 14 (38 per cent) lived more than three years and eight (22 per cent) had no
      cystoscopic or clinical signs of active disease and had normal bladder function.
      Of 23 patients treated more than five years ago, eight were alive after five
      years (35 per cent) and four (17 per cent) remained controlled by radiation
      therapy alone, with normal bladder function.No major complications were observed.
      In particular, no fibrosis of the bladder occurred. Doses ranged from 5,000 r in
      five and a half weeks to 6,000 r in seven weeks.A close cooperation between
      urologic surgeons and radiotherapists during recent years permits long-range
      treatment planning from the time of diagnosis, which is essential in the
      effective therapy of carcinoma of the bladder.

PMID- 18730046
TI  - Statutory consent for chemical test of alcoholic content of blood, breath or
      urine in drunk driving cases.

PMID- 18730045
TI  - Subcutaneous fat necrosis with acute hemorrhagic pancreatitis-a case in a child
      with steroid-resistant nephrosis treated with 6-mercaptopurine.

PMID- 18730047
TI  - Socialism in Saskatchewan: a fiasco.

PMID- 18730048
TI  - Audio-Digest's Benign Cycle.

PMID- 18730049
TI  - For realism in medical legislation.

PMID- 18730050
TI  - Public health report.

PMID- 18730052
TI  - Health care of the people.

PMID- 18730051
TI  - Woman's Auxiliary: American Medical Association Education Research Foundation.

PMID- 18730053
TI  - Blood coagulation and the coumarin anticoagulant drugs.

PMID- 18730054
TI  - The health manpower council.

PMID- 18730055
TI  - Public health report.

PMID- 18730056
TI  - Woman's Auxiliary.

PMID- 18730057
TI  - Professional registered nurses in the United States and california, 1962-report
      of the bureau of research and planning.
AB  - * Figures on professional registered nurses recently made available indicate that
      the ratio of active nurses to population in California in 1962 was 327 per
      100,000 persons. The comparable figure nationally was 298/100,000. California
      ranked twentieth out of the 50 states and the District of Columbia.THE PERCENTAGE
      OF ALL NURSES ACTIVELY ENGAGED IN NURSING IS CONSIDERABLY LOWER IN CALIFORNIA
      THAN IN THE TOTAL UNITED STATES: 60.4 per cent compared with 65.3 per cent. This
      indicates that the shortage of nurses in California is more attributable to
      underutilization of potential manpower than to its absence.There are some
      identifiable categories of nurses in California in which the utilization of
      personnel is particularly low, as compared with other states. In terms of rates
      of utilization, the group of nurses over 60 years of age are most noticeably
      under-utilized, while in terms of numbers, married nurses could provide the
      greatest supply of extra nurses were their employment rate in the state equal to
      the national rate.The recruiting potential is a very great one, however, as this
      report indicates.

PMID- 18730058
TI  - Medicolegal responsibilities in physician-laboratory relations.

PMID- 18730060
TI  - A successful annual meeting.

PMID- 18730059
TI  - Recent concepts in the clinical pharmacology of anithypertensive drugs.
AB  - As yet, no perfect drug has been found which can reduce supine and standing blood
      pressure equally, alter primarily peripheral vascular resistance, increase flow
      to the kidneys and be free of untoward effects. The thiazides, which act directly
      on the vessels and alpha methyl dopa, which causes an incomplete sympathetic
      blockade, are the two agents which come closest to the ideal. The advances which
      have resulted from the discovery of the false neurotransmitters may be expected
      to lead to the discovery of non-toxic drugs which cause subtle changes in the
      nerve ending and more controlled sympathetic blockade.

PMID- 18730061
TI  - The chairman retires.

PMID- 18730062
TI  - Quality of health care.

PMID- 18730063
TI  - Woman's Auxiliary: Membership.

PMID- 18730064
TI  - Letters to editor.

PMID- 18730065
TI  - Ethical Responsibilities in Prescribing Drugs and Devices-Statement of the AMA
      Judicial Council.

PMID- 18730066
TI  - Intracardiac Shunt-Use of the Hydrogen-Sensitive Catheter to Clarify False
      Positive Diagnosis of Left-to-Right Shunt.
AB  - The charts of 142 patients who had diagnostic right heart catheterization with
      conventional oximetry, oxygen content determinations and hydrogen electrode curve
      recording for left-to-right shunt were reviewed. A false positive diagnosis of
      surgical significance would have been made in nine patients if the hydrogen
      electrode had not been used. In addition, a diagnosis of left-to-right shunt
      could have been made at the wrong chamber level in three additional cases.

PMID- 18730067
TI  - Woman's Auxiliary: Rx for Progress.

PMID- 18730068
TI  - Letters to editor.

PMID- 18730069
TI  - New President-Elect Of the AMA.

PMID- 18730070
TI  - A memorial for dr. Charles e. Smith.

PMID- 18730071
TI  - Abnormalities of the placenta and newborn infant.

PMID- 18730072
TI  - Planning and goals in continuing medical education.

PMID- 18730073
TI  - A new executive director.

PMID- 18730074
TI  - Public health report.

PMID- 18730075
TI  - CMA's Position on Medi-Cal's Straits.

PMID- 18730076
TI  - Woman's Auxiliary.

PMID- 18730077
TI  - Professional Courtesy-AMA Judicial Council: Adopted by Judicial Council of the
      American Medical Association 17 June 1967.

PMID- 18730079
TI  - For new directions, new directors.

PMID- 18730078
TI  - Public health report.

PMID- 18730081
TI  - The Shaping of Medicine's Future.

PMID- 18730080
TI  - Public health report.

PMID- 18730083
TI  - Veterinary research.

PMID- 18730082
TI  - Not to take a total loss.

PMID- 18730084
TI  - Woman's Auxiliary: Courier.

PMID- 18730085
TI  - Public health report.

PMID- 18730086
TI  - An Editor's Farewell.

PMID- 18730087
TI  - Public health report.

PMID- 18730088
TI  - Woman's Auxiliary: International Health Activities.

PMID- 18730089
TI  - Trophoblastic tumors of the uterus-problems of methotrexate therapy.
AB  - Nineteen patients with trophoblastic tumors of the uterus were evaluated at the
      University of California San Francisco Medical Center. Eight patients, admitted
      before 1956, did not receive chemotherapy; the mortality rate was 87.5 per cent.
      Ten of the remaining 11 patients were given intermittent, intensive Methotrexate
      therapy; actinomycin D and vincristine were used in treating two patients in whom
      resistance to Methotrexate developed. The mortality was 10 per cent. Toxicity was
      a prominent factor but was completely reversible when chemotherapy was
      stopped.None of the patients showed recurrent disease during follow-up evaluation
      eight months to five years and eight months after therapy was completed.It is
      postulated that continuing chemotherapy four to six months after the chorionic
      gonadotropin titer becomes negative decreases recurrent disease.

PMID- 18730090
TI  - Leukemia in animals and man.
AB  - General comparative aspects of leukemia were reviewed. Leukemia in adult cattle
      occurs frequently within certain multiple case herds. Cattle in these herds often
      have persistent lymphocytosis and increased numbers of atypical lymphocytes in
      blood. Attempts are being made to demonstrate the frequency in which this is a
      "pre-leukemic" or "perileukemic" condition.With the recognition of viral
      causative agent(s) in chickens, laboratory rodents and cats, there is increased
      interest in the leukemia of dogs, cattle and other animals, for the disease in
      these animals may serve as valuable models in the study and isolation of human
      leukemogenic agents.Epidemiologic and clinicopathologic aspects of animal
      leukemias share comparative similarities with themselves and with lymphoreticular
      neoplasms of man. Causative factor(s) probably act on the host, regardless of
      species, in a similar fashion. It is not likely, but neither improbable, that
      leukemia in domesticated animals and leukemia in man share common causal
      relationships.

PMID- 18730091
TI  - Occlusive disease of the vessels of the aortic arch-diagnosis and management.
AB  - Physicians should be alert to the possibility of occlusion of one or more of the
      branches of the aortic arch in any patient having neurologic symptoms or
      complaint of claudication in the upper extremities. The finding of a pulse
      deficit in the neck or arm and a blood pressure difference of more than 30 mm of
      mercury between the two arms is pathognomic of this disease. The presence of the
      occlusive process can be confirmed and its extent determined by
      angiography.Vascular reconstruction can be expected to restore normal
      hemodynamics with gratifying relief of symptoms in the majority of cases.

PMID- 18730092
TI  - Muscle weakness and atrophy-clinical and laboratory evaluation.
AB  - A thorough family history, the age at the time of onset and detailed information
      regarding the rate, mode of progression and distribution of weakness is needed
      for evaluation of patients with weakness and atrophy. Associated findings such as
      dermal lesions, tenderness, myotonia and fasciculations should also be noted.The
      major diagnostically useful laboratory tests are electromyography, nerve
      conduction, serum enzyme levels and muscle biopsy.Each clinical and laboratory
      finding should be categorized in terms of its neuro-anatomical origin, since
      weakness may result from disturbances in the corticospinal pathways, the lower
      motor neuron, the myoneural junction and the muscle.

PMID- 18730093
TI  - Failure to thrive-an analysis of 83 cases.
AB  - The case histories of 83 children admitted to the hospital with a diagnosis only
      of failure to thrive were examined. In twenty-six cases there was evidence of
      maternal deprivation as a factor. Forty patients were found to have significant
      organic diseases as a possible or probable cause or contributing influence.Twenty
      six were found to have some degree of mental retardation, either documented or
      suspected, but in nearly all of them there were associated factors presumably
      responsible, at least in part, for failure to thrive.Several children had birth
      weight less than 2,500 grams, but no child was thought to grow poorly because of
      prematurity alone. Congenital anomalies such as cleft palate and other problems
      leading to feeding difficulties were not unusual.In any case of persistent
      failure of an infant to gain adequately in weight and length, in which the cause
      is not evident, the child should be admitted to a hospital to determine response
      in a new environment. Also an adequate social history should be sought and
      siblings more closely evaluated; and careful study should be made of the renal,
      gastro-intestinal, cardiac, pulmonary and central nervous systems, even if there
      are no symptoms or signs referable to these systems.

PMID- 18730094
TI  - Drip infusion pyelography-valuable supplement to the inconclusive intravenous
      pyelogram.
AB  - By comparative studies of films, the superiority of infusion pyelography over
      conventional intravenous pyelography was confirmed.The technique is shown to be
      safe, even in the presence of uremia, diabetes, cardiovascular disease and
      advanced age.It is well suited for outpatient use, and should reduce the need for
      retrograde uretero-pyelography to supplement the diagnostically inconclusive
      intravenous pyelogram.

PMID- 18730096
TI  - Regional medical programs.

PMID- 18730095
TI  - Effects of automation on laboratory diagnosis.
AB  - THERE ARE FOUR PRIMARY EFFECTS OF LABORATORY AUTOMATION ON THE PRACTICE OF
      MEDICINE: The range of laboratory support is being greatly extended to both
      diagnosis and guidance of therapeutic management; the new feasibility of
      multiphasic periodic health evaluation promises effective health and manpower
      conservation in the future; and substantially lowered unit cost for laboratory
      analysis will permit more extensive use of comprehensive laboratory medicine in
      everyday practice. There is, however, a real and growing danger of naive
      acceptance of and overconfidence in the reliability and accuracy of automated
      analysis and computer processing without critical evaluation. Erroneous results
      can jeopardize the patient's welfare. Every physician has the responsibility to
      obtain proof of accuracy and reliability from the laboratories which serve his
      patients.

PMID- 18730097
TI  - A conference at chandler.

PMID- 18730098
TI  - Gynecomastia, hypospermatogenesis and a large y chromosome in a man.

PMID- 18730099
TI  - Obstruction of large bowel due to fecaloma-successful medical treatment in two
      cases.

PMID- 18730100
TI  - Interstitial abdominal emphysema (pneumatosis cystoides intestinalis).

PMID- 18730102
TI  - A great editor.

PMID- 18730101
TI  - Choriocarcinoma, a landmark in cancer chemotherapy.

PMID- 18730103
TI  - A third force.

PMID- 18730104
TI  - Woman's Auxiliary: Health Careers.

PMID- 18730105
TI  - Lester breslow.

PMID- 18730106
TI  - Two centennials.

PMID- 18730107
TI  - Peritoneal dialysis in chronic uremia.

PMID- 18730108
TI  - The scope of medicine.

PMID- 18730109
TI  - A century of restless progress.

PMID- 18730111
TI  - Chemical examination.

PMID- 18730110
TI  - Sacramento society for medical improvement: the centennial.

PMID- 18730112
TI  - A commission on medical economics.

PMID- 18730114
TI  - A fine program well presented.

PMID- 18730113
TI  - Woman's Auxiliary: Ama-Erf.

PMID- 18730115
TI  - The baby and the bath water.

PMID- 18730116
TI  - Erythrocyte enzyme defects.

PMID- 18730117
TI  - Nerve entrapment in the upper extremity.

PMID- 18730118
TI  - Woman's Auxiliary: What is Wa-Sama?

PMID- 18730119
TI  - Biochemistry and mental States.

PMID- 18730120
TI  - The confusion of tongues.

PMID- 18730122
TI  - Abdominal aortic aneurysms.

PMID- 18730121
TI  - Physician manpower.

PMID- 18730123
TI  - A history of leadership.

PMID- 18730125
TI  - Welcome AMA.

PMID- 18730124
TI  - Comprehensive health planning in san diego.

PMID- 18730126
TI  - A new kind of forum.

PMID- 18730127
TI  - Routine chemical screening.

PMID- 18730128
TI  - Current knowledge of psoriasis.

PMID- 18730129
TI  - A biologic society in an age of science.

PMID- 18730131
TI  - Carpal tunnel syndrome.

PMID- 18730130
TI  - Incredible.

PMID- 18730132
TI  - Dissent.

PMID- 18730134
TI  - Public health report.

PMID- 18730133
TI  - Student loan fund.

PMID- 18730135
TI  - Systemic management of malignant disease.

PMID- 18730136
TI  - An Illogicity to be Avoided.

PMID- 18730137
TI  - Treatment of viral infections?

PMID- 18730138
TI  - Medicine and human behavior.

PMID- 18730139
TI  - A new director of public health.

PMID- 18730141
TI  - Let's Turn On.

PMID- 18730140
TI  - THE SCOPE AND RESPONSIBILITY OF MEDICINE-A Forum with a Purpose.
AB  - To engender discussion of what the scope and responsibility of medicine ought to
      be in today's society, California Medicine printed in its June issue six essays
      by authors known to have keen if various interest in the subject.In presenting
      the essays the editors expressed hope that they would be the beginning of a forum
      from which a definition of our profession's responsibilities may be distilled.
      Readers were invited to take part in a continuation of the forum in succeeding
      issues. Following are three contributions selected from those received to date.
      Others will be published in the months ahead.If you have thoughts on the subject,
      just address them to the editors of California Medicine, 693 Sutter Street, San
      Francisco, California 94102. Keep your essays short, please.

PMID- 18730142
TI  - Treatment of acute leukemia.

PMID- 18730143
TI  - Prevention of ischemic vascular disease.

PMID- 18730144
TI  - Health data.

PMID- 18730145
TI  - Strong stimuli.

PMID- 18730146
TI  - Public health report.

PMID- 18730147
TI  - THE SCOPE AND RESPONSIBILITY OF MEDICINE-A Forum with a Purpose.
AB  - To engender discussion of what the scope and responsibility of medicine ought to
      be in today's society, California Medicine printed in its June issue six essays
      by authors known to have keen if various interest in the subject.In presenting
      the essays the editors expressed hope that they would be the beginning of a forum
      from which a definition of our profession's responsibilities may be distilled.
      Readers were invited to take part in a continuation of the forum in succeeding
      issues. Following are three contributions selected from those received to date.
      Others will be published in the months ahead.If you have thoughts on the subject,
      just address them to the editors of California Medicine, 693 Sutter Street, San
      Francisco, California 94102. Keep your essays short, please.

PMID- 18730148
TI  - LATS and the Thyroid Gland.

PMID- 18730150
TI  - Doctrine in an age of science.

PMID- 18730149
TI  - Continuing his education.

PMID- 18730151
TI  - Changing concepts of coronary care.

PMID- 18730152
TI  - Woman's Auxiliary: Community Health-A Challenge.

PMID- 18730153
TI  - A conference on the planning process.

PMID- 18730154
TI  - Bridges across the gap.

PMID- 18730155
TI  - Which new penicillin?

PMID- 18730156
TI  - Medicare today and tomorow.

PMID- 18730157
TI  - Treatment of acute leukemia.

PMID- 18730158
TI  - What goes on?

PMID- 18730159
TI  - Public health report.

PMID- 18730160
TI  - THE SCOPE AND RESPONSIBILITY OF MEDICINE-A Forum with a Purpose.
AB  - To engender discussion of what the scope and responsibility of medicine ought to
      be in today's society, California Medicine printed in its June issue six essays
      by authors known to have keen if various interest in the subject.In presenting
      the essays the editors expressed hope that they would be the beginning of a forum
      from which a definition of our profession's responsibilities may be distilled.
      Readers were invited to take part in a continuation of the forum in succeeding
      issues. Following are three contributions selected from those received to date.
      Others will be published in the months ahead.If you have thoughts on the subject,
      just address them to the editors of California Medicine, 693 Sutter Street, San
      Francisco, California 94102. Keep your essays short, please.

PMID- 18730161
TI  - Rising health care costs.

PMID- 18730162
TI  - If one drug is good, then two drugs are better?

PMID- 18730163
TI  - A recognition well earned.

PMID- 18730164
TI  - Carcinoma in situ of the uterine cervix.

PMID- 18730165
TI  - The tuberculosis problem today.

PMID- 18730166
TI  - Public health report.

PMID- 18730167
TI  - Woman's Auxiliary: The Courier.

PMID- 18730169
TI  - A call to action.

PMID- 18730168
TI  - THE SCOPE AND RESPONSIBILITY OF MEDICINE - A Statement Drawn from Contributions
      to a Forum.
AB  - This statement was prepared from published and unpublished contributions to a
      national forum on the scope and responsibility of medicine recently conducted by
      California Medicine. The editors hope this distillate of the discussions will
      prove useful to the profession and to the public, and they also wish to express
      their appreciation to all those in California and elsewhere who have contributed
      to this forum.

PMID- 18730170
TI  - Elections and illusions.

PMID- 18730171
TI  - Surgical operation for heart failure.

PMID- 18730172
TI  - Progress in reproductive endocrinology.

PMID- 18730173
TI  - Mycosis fungoides.

PMID- 18730174
TI  - Responsibility of medical schools.

PMID- 18730175
TI  - Acute renal failure due to a bismuth preparation.

PMID- 18730176
TI  - Woman's Auxiliary: Physicians' Benevolence Fund, Inc.

PMID- 18730178
TI  - Management of rheumatoid arthritis.

PMID- 18730177
TI  - Public health report.

PMID- 18730179
TI  - New scientific stature.

PMID- 18730180
TI  - Biologic science and human equality.

PMID- 18730181
TI  - Medi-cal and the legislature.

PMID- 18730182
TI  - Pre-cancer test.

PMID- 18730183
TI  - Limits on pap smear under medicare.

PMID- 18730184
TI  - Indwelling plastic intravenous cannulas.

PMID- 18730185
TI  - Woman's Auxiliary: Health Careers.

PMID- 18730187
TI  - A word of thanks.

PMID- 18730186
TI  - Public health report.

PMID- 18730188
TI  - PRESIDENT'S PAGE: What Do the Dues Do?

PMID- 18730190
TI  - Keeping abreast of inflation.

PMID- 18730189
TI  - Drug interactions.

PMID- 18730191
TI  - The second national congress on medical ethics.

PMID- 18730193
TI  - Public health report.

PMID- 18730192
TI  - Woman's Auxiliary: Ama-Erf.

PMID- 18730194
TI  - A sequence of change.

PMID- 18730196
TI  - Indigenous health aides.

PMID- 18730195
TI  - Gout and hyperuricemia.

PMID- 18730197
TI  - The Fear of Women-or Our Debt to Book Reviewers.

PMID- 18730198
TI  - Public health report.

PMID- 18730199
TI  - Management of psychomotor (temporal lobe) seizures.

PMID- 18730200
TI  - Phenformin and lactic acidosis.

PMID- 18730201
TI  - A physician is worthy of his hire.

PMID- 18730202
TI  - On polluting the biosphere.

PMID- 18730203
TI  - More on rh immunization.

PMID- 18730204
TI  - Usual, customary and reasonable.

PMID- 18730206
TI  - Rh nomenclature.

PMID- 18730205
TI  - Secondary syphilis diagnosed as mononucleosis.

PMID- 18730207
TI  - Public health report.

PMID- 18730208
TI  - The health care dollar-some factors affecting costs and value received.

PMID- 18730209
TI  - Oversell and undersell.

PMID- 18730210
TI  - Medicine and the new human condition.

PMID- 18730211
TI  - Whose momism?

PMID- 18730212
TI  - Public health report.

PMID- 18730213
TI  - Induced abortion and the law.

PMID- 18730214
TI  - On polluting the biosphere.

PMID- 18730216
TI  - Letter to a medical student.

PMID- 18730215
TI  - Your Office Assistant and the CMAA.

PMID- 18730217
TI  - Portal hypertension.

PMID- 18730218
TI  - Welcome NMA.

PMID- 18730220
TI  - The specter of malpractice.

PMID- 18730219
TI  - Abdominal aortic aneurysm: a surgical disease.

PMID- 18730221
TI  - Power tactics in health care.

PMID- 18730223
TI  - The new assistant secretary.

PMID- 18730222
TI  - School health-history forms.

PMID- 18730224
TI  - A midsummer pipe dream.

PMID- 18730225
TI  - Bridging the generation gap: a progress note.

PMID- 18730227
TI  - Another wilbur to chicago.

PMID- 18730226
TI  - Medicine and new cultural values: an editorial essay.

PMID- 18730228
TI  - Of privilege and disadvantage.

PMID- 18730229
TI  - A problem and a proposal.

PMID- 18730231
TI  - Professional corporations.

PMID- 18730230
TI  - What and where and when to learn.

PMID- 18730232
TI  - Drowning and hyperventilation syndrome.

PMID- 18730233
TI  - Medicine and the 1970s.

PMID- 18730235
TI  - Universal health insurance.

PMID- 18730234
TI  - An agreement on style for references.

PMID- 18730236
TI  - Principles and practice of podiatry.

PMID- 18730237
TI  - Vasopressin test for assessment of integrity of pituitary-adrenal axis.

PMID- 18730238
TI  - Diagnostic application of immunoglobulin determinations.

PMID- 18730239
TI  - Important advances in clinical medicine.

PMID- 18730240
TI  - Value of total thyroxin and free thyroxin measurements in thyroid evaluation.

PMID- 18730241
TI  - Clinical indications for the analysis of immune globulins.

PMID- 18730242
TI  - Phosphate treatment of hypercalcemia.

PMID- 18730243
TI  - Indications for pacemakers in cardiac disease.

PMID- 18730244
TI  - The clinical use of medium chain triglycerides.

PMID- 18730245
TI  - Disaccharidase deficiency: a clinical reality.

PMID- 18730246
TI  - Use of plasma Renin assays in the evaluation of patients with hypertension.

PMID- 18730247
TI  - Suppression of rh sensitization.

PMID- 18730248
TI  - Diagnosis and treatment of growth hormone deficiency.

PMID- 18730249
TI  - Treatment of hemophilia with newer blood factors.

PMID- 18730250
TI  - Amniocentesis.

PMID- 18730251
TI  - The Pathogenic Role of the EB Virus.

PMID- 18730252
TI  - The clinical use of propranolol.

PMID- 18730254
TI  - Important advances in clinical medicine.

PMID- 18730253
TI  - Effective drug therapy for hyperlipidemia.

PMID- 18730256
TI  - The 99th annual session.

PMID- 18730255
TI  - A fifth progress report.

PMID- 18730258
TI  - CNA Position on the Expanding Role of the Nurse.

PMID- 18730257
TI  - Supermarket medicine.

PMID- 18730259
TI  - Whither nursing?

PMID- 18730260
TI  - Peer review.

PMID- 18730261
TI  - Current status of multiphasic screening.

PMID- 18730262
TI  - Health sciences construction bonds.

PMID- 18730263
TI  - THE HEALTH BONDS: A Mandate for Proposition 1.

PMID- 18730264
TI  - RELEVANCE FOR TODAY AND TOMORROW IN MEDICAL EDUCATION-A Forum.
AB  - Students of today question the relevance of much of their formal education. In
      medical schools the concern is particularly with the relevance of the educational
      experience to the professional commitment in modern society. To engender
      discussion of the subject, California Medicine in its January issue printed eight
      essays by authors known to have keen interest in the subject.Readers in
      California and elsewhere are invited to take part in a continuation of the forum
      in succeeding issues. The following are contributions selected from those
      received to date. Others will be published in the months ahead. At an appropriate
      time the material will be collated and, if feasible, the distillate will be
      prepared in the form of a statement.If you have thoughts on the subject, just
      address them to the editors of California Medicine, 693 Sutter Street, San
      Francisco, California, 94102. Keep your essays short, please.

PMID- 18730265
TI  - Epitomes of progress - pediatrics.

PMID- 18730266
TI  - Rubella vaccine.

PMID- 18730267
TI  - The importance of birthweight to gestational age.

PMID- 18730268
TI  - Amniotic fluid analysis-a cooperative and multidiscipline approach to the
      prevention of certain inherited disorders.

PMID- 18730269
TI  - The use of clotting-factor concentrates for the treatment of hemophilia.

PMID- 18730270
TI  - Current immunization procedures.

PMID- 18730271
TI  - Recognition and treatment of intravascular coagulation.

PMID- 18730272
TI  - The diagnostic application of immunoglobulin determinations.

PMID- 18730273
TI  - Prevention of erythroblastosis with anti-rh gamma globulin.

PMID- 18730274
TI  - Intensive care nursery.

PMID- 18730275
TI  - Phototherapy in the treatment of hyperbilirubinemia.

PMID- 18730276
TI  - Gentamicin in the treatment of gram-negative infections.

PMID- 18730277
TI  - Diagnosis of rubella.

PMID- 18730278
TI  - The Hemagglutination Inhibition (HI) Antibody Test for the Determination Of
      Immunity to Rubella.

PMID- 18730279
TI  - Zoster immune globulin for chickenpox prevention.

PMID- 18730281
TI  - Recognition and treatment of heart disease in the neonate.

PMID- 18730280
TI  - Availability of improved centers for the diagnosis and treatment of children with
      congenital defects, learning and neurological disorders.

PMID- 18730282
TI  - Undernutrition and child development.

PMID- 18730283
TI  - Slow virus infections.

PMID- 18730284
TI  - Child-resistant containers.

PMID- 18730285
TI  - Valium in the treatment of epilepsy.

PMID- 18730286
TI  - Drug abuse.

PMID- 18730287
TI  - Growth retardation in environmental deprivation.

PMID- 18730288
TI  - Intravenous alimentation.

PMID- 18730289
TI  - White house conference on nutrition.

PMID- 18730290
TI  - Gonorrhea and ophthalmia prophylaxis.

PMID- 18730291
TI  - Female of the m.d. Species.

PMID- 18730292
TI  - Epitomes of progress -- surgery.

PMID- 18730293
TI  - Cardiopulmonary resuscitation.

PMID- 18730294
TI  - Circulating antibodies in renal transplant recipients.

PMID- 18730295
TI  - Antilymphocyte Globulin (ALG) in Clinical Organ Transplantation.

PMID- 18730296
TI  - Cadaver organ sharing.

PMID- 18730297
TI  - Cancer immunology.

PMID- 18730299
TI  - Renal transplantation results.

PMID- 18730298
TI  - Surgical management of transposition of the great vessels.

PMID- 18730300
TI  - Resection of dyskinetic ventricular muscle or ventricular aneurysms.

PMID- 18730301
TI  - Use of aortic homograft to replace the aortic or mitral valve.

PMID- 18730302
TI  - Saphenous vein bypass for coronary artery occlusive disease.

PMID- 18730303
TI  - Advantages of continuous positive-pressure breathing in surgical patients.

PMID- 18730305
TI  - Recurrence in colon carcinoma.

PMID- 18730304
TI  - Radioimmunoassay of gastrin.

PMID- 18730306
TI  - Emergency portacaval shunt for bleeding esophageal varices.

PMID- 18730307
TI  - Newer concepts in the management of shock.

PMID- 18730308
TI  - Blood supply to stomach.

PMID- 18730309
TI  - A medical student responds to a question.

PMID- 18730310
TI  - Medical school graduates for patient care.

PMID- 18730311
TI  - MEDEX Program.

PMID- 18730312
TI  - More nutrition.

PMID- 18730313
TI  - Perinatal pulmonary roentgenography.

PMID- 18730314
TI  - Epitomes of progress -- radiology.

PMID- 18730315
TI  - Posterior fossa aneurysm presenting as mass lesions.

PMID- 18730316
TI  - Genus varus and valgus in children.

PMID- 18730317
TI  - Multiple progressive intracranial arterial occlusion of children and young
      adults.

PMID- 18730318
TI  - The roentgenologic diagnosis of lactase deficiency.

PMID- 18730319
TI  - Spontaneous closure of acute traumatic renal arteriovenous fistulas.

PMID- 18730321
TI  - Renal vein thrombosis.

PMID- 18730320
TI  - Adrenal venography.

PMID- 18730322
TI  - Preliminary sensitivity testing in intravenous pyelography.

PMID- 18730323
TI  - Splanchnic artery stenosis and occlusion.

PMID- 18730324
TI  - Selective arteriography in locating the site of gastrointestinal hemorrhage.

PMID- 18730325
TI  - Contrast laryngography.

PMID- 18730326
TI  - Hypotonic duodenography.

PMID- 18730327
TI  - Pulmonary leiomyoma.

PMID- 18730328
TI  - Percutaneous transtracheal bronchography.

PMID- 18730329
TI  - Frequency of urinary tract abnormalities in sickle cell disease.

PMID- 18730330
TI  - Rapid Sequence IVP in Hypertension.

PMID- 18730331
TI  - Radionuclide studies of pulmonary ventilation and perfusion.

PMID- 18730332
TI  - Translumbar pyelography in children.

PMID- 18730333
TI  - The osteochondroses.

PMID- 18730334
TI  - Intravenous pyelography in azotemia.

PMID- 18730336
TI  - Isotope lung scanning in pediatric respiratory disease.

PMID- 18730335
TI  - Growth lines.

PMID- 18730337
TI  - Congenital bone lesions following fetal viremia.

PMID- 18730338
TI  - Cerebrospinal fluid dynamics studied with radionuclides.

PMID- 18730339
TI  - Radionuclide angiography.

PMID- 18730340
TI  - RELEVANCE FOR TODAY AND TOMORROW IN MEDICAL EDUCATION-A Forum.
AB  - Students of today question the relevance of much of their formal education. In
      medical schools the concern is particularly with the relevance of the educational
      experience to the professional commitment in modern society. To engender
      discussion of the subject, California Medicine in its January issue printed eight
      essays by authors known to have keen interest in the subject.Readers in
      California and elsewhere are invited to take part in a continuation of the forum
      in succeeding issues. The following are contributions selected from those
      received to date. Others will be published in the months ahead. At an appropriate
      time the material will be collated and, if feasible, the distillate will be
      prepared in the form of a statement.If you have thoughts on the subject, just
      address them to the editors of California Medicine, 693 Sutter Street, San
      Francisco, California, 94102. Keep your essays short, please.

PMID- 18730341
TI  - World medicine and the coming millennium.

PMID- 18730342
TI  - A word about "epitomes".

PMID- 18730343
TI  - The myths and the words.

PMID- 18730344
TI  - Relevance in medical education.

PMID- 18730345
TI  - Dr. Lloyd H. Smith, Jr., Named to President's Science Advisory Committee.

PMID- 18730346
TI  - Summary of activities in california - september 1968-august 1969.

PMID- 18730347
TI  - Epitomes of progress -- allergy.

PMID- 18730348
TI  - The house dust mite.

PMID- 18730349
TI  - Immunoglobulin e in allergic disease.

PMID- 18730350
TI  - The use of disodium cromoglycate in the treatment of asthma.

PMID- 18730351
TI  - Recent laboratory evidence of benefits from injection therapy for pollinosis.

PMID- 18730352
TI  - The use of immune serum globulin (gamma globulin).

PMID- 18730353
TI  - New information on allergic rhinitis.

PMID- 18730354
TI  - Immunoglobulin IgA.

PMID- 18730355
TI  - Hypersensitivity to organic dusts.

PMID- 18730357
TI  - Hereditary angio-edema.

PMID- 18730356
TI  - The Beta-adrenergic blockade hypothesis of asthma.

PMID- 18730358
TI  - Newer trends in corticosteroid therapy.

PMID- 18730359
TI  - Aspirin sensitivity.

PMID- 18730360
TI  - The management of respiratory failure in childhood status asthmaticus.

PMID- 18730361
TI  - Hypoxia in asthmatic attacks.

PMID- 18730363
TI  - Life-threatening asthma.

PMID- 18730362
TI  - Pathology of bronchial obstruction in asthma.

PMID- 18730364
TI  - The allergic tension-fatigue syndrome.

PMID- 18730365
TI  - Ferment in medical education.

PMID- 18730366
TI  - Capitation health care.

PMID- 18730367
TI  - On quick test uses.

PMID- 18730369
TI  - Fads, facts, fundamentals.

PMID- 18730368
TI  - Amniocentesis registry.

PMID- 18730370
TI  - CMA and the Seventies.

PMID- 18730371
TI  - Epitomes of progress -- preventive medicine and public health.

PMID- 18730372
TI  - Dangerous drugs.

PMID- 18730373
TI  - Improved antimicrobial susceptibility testing in clinical microbiology
      laboratories.

PMID- 18730374
TI  - California drug science 1970.

PMID- 18730375
TI  - Quackery.

PMID- 18730376
TI  - Carbon monoxide as community air pollutant.

PMID- 18730378
TI  - School children and pesticides.

PMID- 18730377
TI  - DDT Out-Organophosphates Also Dangerous.

PMID- 18730379
TI  - The control of rubella.

PMID- 18730381
TI  - Nutrition.

PMID- 18730380
TI  - X-ray Mammography And Thermography In Breast Cancer.

PMID- 18730382
TI  - Cytologic examination for cervical cancer.

PMID- 18730383
TI  - Pregnant teenagers.

PMID- 18730384
TI  - Students in politics.

PMID- 18730385
TI  - A New SAMA President.

PMID- 18730386
TI  - The relationships of medicine.

PMID- 18730388
TI  - Relate "relevance" to problems.

PMID- 18730387
TI  - Definition of health.

PMID- 18730389
TI  - Gonococcal conjunctivitis of the newborn.

PMID- 18730390
TI  - A way to make more medical "schools".

PMID- 18730391
TI  - Costly mythology in health care.

PMID- 18730392
TI  - Measles in california.

PMID- 18730393
TI  - The outlook for patients with severe acquired valvular aortic stenosis.

PMID- 18730394
TI  - Epitomes of progress -- pathology.

PMID- 18730396
TI  - Blood Component Therapy: Packed Red Blood Cells versus Whole Blood.

PMID- 18730395
TI  - Cryoprecipitate in the treatment of hemophilia.

PMID- 18730397
TI  - Preoperative screening for bleeding diathesis.

PMID- 18730398
TI  - Proven and possible future uses of anti-rh gamma globulin.

PMID- 18730399
TI  - Preservation and transplantation of human cadaver kidneys.

PMID- 18730400
TI  - Medical curricula: relevance then to now, and now to now.

PMID- 18730402
TI  - Diagnosis of obstructive jaundice.

PMID- 18730401
TI  - Population control: is there another side to the coin?

PMID- 18730403
TI  - Proposition 1.

PMID- 18730404
TI  - Cancer of the female breast yesterday, today and tomorrow.

PMID- 18730406
TI  - A new ethic for medicine and society.

PMID- 18730405
TI  - New Ideas about Myasthenia Gravis.

PMID- 18730407
TI  - Who is supposed to be doing what?

PMID- 18730408
TI  - Add fads, facts, fundamentals.

PMID- 18730409
TI  - Quick replies.

PMID- 18730410
TI  - The distribution of population growth.

PMID- 18730411
TI  - Imported diseases.

PMID- 18730412
TI  - Antimalarial drugs in dermatology.

PMID- 18730413
TI  - Liver disease, psoriasis, and methotrexate.

PMID- 18730414
TI  - Photocontact dermatitis.

PMID- 18730415
TI  - Enzyme defect in xeroderma pigmentosum.

PMID- 18730416
TI  - Allergic contact dermatitis: recent problems.

PMID- 18730417
TI  - Recent advances in leprosy.

PMID- 18730419
TI  - Fluorescent tests in the diagnosis of pemphigus, pemphigoid and lupus
      erythematosus.

PMID- 18730418
TI  - Phlebotomy therapy for porphyria cutanea tarda.

PMID- 18730420
TI  - 5-Fluorouracil in the treatment of actinic keratosis.

PMID- 18730421
TI  - Treponema pallidum in treated syphilis.

PMID- 18730422
TI  - Racism and medicine.

PMID- 18730423
TI  - Further notes on curricula.

PMID- 18730424
TI  - One mental health approach to fostering world peace.

PMID- 18730425
TI  - Population density and social pathology.

PMID- 18730426
TI  - WOMAN'S AUXILIARY-"You Can Always Recycle a Towel".

PMID- 18730427
TI  - Population problems.

PMID- 18730429
TI  - Epitomes of progress -- plastic surgery.

PMID- 18730428
TI  - Recent advances in microsurgery.

PMID- 18730430
TI  - Social responsibilities of the plastic surgeon.

PMID- 18730431
TI  - Physician's Assistants Training Program.

PMID- 18730432
TI  - The present status of the silicones.

PMID- 18730433
TI  - Transsexual surgery.

PMID- 18730434
TI  - The island pedicle flap.

PMID- 18730435
TI  - New advances in the topical treatment of burns.

PMID- 18730436
TI  - A new concept in burn care.

PMID- 18730437
TI  - A changed medical view of "cleft palate speech".

PMID- 18730438
TI  - Modification of wound healing patterns.

PMID- 18730439
TI  - The present status of breast augmentation.

PMID- 18730441
TI  - Correction of drooling in cerebral palsy.

PMID- 18730440
TI  - Silastic(R) joint prosthesis in the hand.

PMID- 18730442
TI  - Immediate reconstruction after radical cancer operations on the head and neck.

PMID- 18730443
TI  - Nasal ethmoidal fractures.

PMID- 18730444
TI  - Dissociative anesthesia.

PMID- 18730445
TI  - Proposed Amendments to the CMA Constitution for Action in 1971.

PMID- 18730446
TI  - Epitomes of progress -- obstetrics and gynecology.

PMID- 18730447
TI  - Nettlesome minority.

PMID- 18730448
TI  - Epitomes of progress -- orthopedics.

PMID- 18730449
TI  - Total hip replacement.

PMID- 18730450
TI  - Surgical treatment of rheumatoid arthritis in the hands.

PMID- 18730451
TI  - The use of compression plates for fractures.

PMID- 18730452
TI  - New concepts of sterile conditions in the operating room.

PMID- 18730454
TI  - Unstable knee.

PMID- 18730453
TI  - Ambulatory treatment of legg-calves-perthes syndrome.

PMID- 18730455
TI  - Recent advances in the treatment of arthritis of the knee.

PMID- 18730457
TI  - Immediate postsurgical prosthetic fitting for lower extremity amputations.

PMID- 18730456
TI  - Treatment of fractures of the leg by modified casting and early weight-bearing.

PMID- 18730458
TI  - The 100th annual scientific assembly.

PMID- 18730459
TI  - Chemicals in the environment.

PMID- 18730460
TI  - Do not smoke in front of your dog.

PMID- 18730462
TI  - Where's the Action?

PMID- 18730461
TI  - A new ethic for medicine and society.

PMID- 18730463
TI  - Orthopedic ecology.

PMID- 18730465
TI  - A new ethic for medicine and society.

PMID- 18730464
TI  - A new ethic for medicine and society.

PMID- 18730467
TI  - Proposed Amendments to the CMA Constitution for Action in 1971.

PMID- 18730466
TI  - A critical comment.

PMID- 18730468
TI  - Epitomes of progress -- urology.

PMID- 18730469
TI  - Drip infusion pyelography in renal injuries.

PMID- 18730470
TI  - Dependability of Renin in the diagnosis of renal hypertension.

PMID- 18730471
TI  - Treatment of undescended testes.

PMID- 18730472
TI  - Chronic bacterial prostatitis and the problem of antibiotic diffusion.

PMID- 18730473
TI  - "Right on!".

PMID- 18730474
TI  - A Timely Correspondence (Between the Late Dr. Ray Lyman Wilbur and the then
      Governor of California, Earl Warren).

PMID- 18730475
TI  - A Timely Correspondence (Between the Late Dr. Ray Lyman Wilbur and the then
      Governor of California, Earl Warren).

PMID- 18730476
TI  - A Timely Correspondence (Between the Late Dr. Ray Lyman Wilbur and the then
      Governor of California, Earl Warren).

PMID- 18730478
TI  - Further Words About DDT.

PMID- 18730477
TI  - Further Words About DDT.

PMID- 18730479
TI  - Further Words About DDT.

PMID- 18730480
TI  - Further Words About DDT.

PMID- 18730481
TI  - A Student's Comments.

PMID- 18730482
TI  - California's Retail Food Inspection Program.

PMID- 18730483
TI  - Pulmonary embolectomy.

PMID- 18730484
TI  - Epitomes of progress -- general surgery.

PMID- 18730485
TI  - Surgical management of coronary artery disease and its sequelae.

PMID- 18730486
TI  - Intravenous hyperalimentation.

PMID- 18730487
TI  - Valve replacement.

PMID- 18730488
TI  - Intestinal atresia as a complication of intrauterine disease processes.

PMID- 18730489
TI  - Subphrenic abscess.

PMID- 18730490
TI  - Renal transplantation-cadaveric donor.

PMID- 18730492
TI  - Renal transplantation-types and mechanisms of "rejection".

PMID- 18730491
TI  - Current results with renal transplantation-related donors.

PMID- 18730493
TI  - Specific immunosuppression-enhancement or immunologic tolerance.

PMID- 18730494
TI  - Heart transplantation.

PMID- 18730496
TI  - Transplantation of other organs.

PMID- 18730495
TI  - Hepatic transplantation.

PMID- 18730497
TI  - Hepatitis in patients undergoing hemodialysis or transplantation.

PMID- 18730498
TI  - New Directions for RMP.

PMID- 18730499
TI  - Of life styles and health care.

PMID- 18730500
TI  - Mid-trimester abortions, fetal weight and ethics.

PMID- 18730501
TI  - Prepare for (the Right) Action.

PMID- 18730502
TI  - The medi-cal cuts.

PMID- 18730503
TI  - SAMA Summer Preceptorship Program.

PMID- 18730504
TI  - Chemotherapy of amebiasis.

PMID- 18730505
TI  - Metachronous development of regional enteritis of the colon in a patient with
      ulcerative colitis.

PMID- 18730506
TI  - The Physician's Role in Venereal Disease Control.

PMID- 18730507
TI  - Aldosterone levels.

PMID- 18730508
TI  - Epitomes of progress -- pathology.

PMID- 18730509
TI  - Selective deficiency of immunoglobulin a (IgA) and autoimmunity.

PMID- 18730511
TI  - Detection of immune complexes in human serum by precipitin reaction with clq
      component of complement.

PMID- 18730510
TI  - C3 lytic factor in nephritis.

PMID- 18730512
TI  - Diagnosis of respiratory distress syndrome (hyaline membrane disease) by
      amniocentesis.

PMID- 18730513
TI  - Mechanisms of blood clotting.

PMID- 18730515
TI  - Implication of epstein-barr virus in human disease.

PMID- 18730514
TI  - Practical application of the use of immunofluorescence in renal biopsy.

PMID- 18730516
TI  - Pituitary hormone assay.

PMID- 18730517
TI  - Computer-based inventory and information systems for blood banks.

PMID- 18730519
TI  - Prevention of viral hepatitis.

PMID- 18730518
TI  - Slow virus infection of nervous tissue.

PMID- 18730520
TI  - Platelet typing.

PMID- 18730521
TI  - Prenatal diagnosis of genetic disease.

PMID- 18730522
TI  - Herpes virus.

PMID- 18730524
TI  - Diagnosis of death due to insulin overdosage.

PMID- 18730523
TI  - Complications of drug abuse.

PMID- 18730525
TI  - IgM Screening of the Newborn.

PMID- 18730526
TI  - Of pharmacists, physicians and health care.

PMID- 18730527
TI  - A matter of reverences.

PMID- 18730528
TI  - Tumor immunology.

PMID- 18730529
TI  - The consent to treatment, in reverse.

PMID- 18730531
TI  - Methadone Maintenance Techniques-AMA Statement.

PMID- 18730530
TI  - More fads, facts, fundamentals.

PMID- 18730532
TI  - Induced vivax malaria among users of intravenous heroin.

PMID- 18730533
TI  - Epitomes of progress -- pediatrics.

PMID- 18730534
TI  - Dialysis and homotransplantation in children.

PMID- 18730535
TI  - Developmental biochemistry of the intestine.

PMID- 18730536
TI  - Disseminated intravascular coagulation.

PMID- 18730537
TI  - Antiviral therapy in abnormally susceptible patients.

PMID- 18730539
TI  - Measles vaccine updated.

PMID- 18730538
TI  - Synthesis of human growth hormone.

PMID- 18730540
TI  - Phototherapy for the jaundiced infant.

PMID- 18730541
TI  - Important advances in phenylketonuria.

PMID- 18730542
TI  - Advances in prenatal detection of genetic disease.

PMID- 18730543
TI  - Simultaneous use of multiple drugs.

PMID- 18730544
TI  - Rubella vaccine.

PMID- 18730545
TI  - Newborn special care.

PMID- 18730547
TI  - On cutting costs in health care.

PMID- 18730546
TI  - Effects of perinatal nutrition on CNS development and function.

PMID- 18730548
TI  - Dealing in futures-part I: in medicine and health care.

PMID- 18730549
TI  - Shall Organized Medicine be Unified, or Separate?
AB  - At present, physicians in California who choose to join organized medicine do so
      through their county medical societies, and membership in the California Medical
      Association and the American Medical Association is then automatic. At the March
      meeting of the CMA House of Delegates, question was raised whether membership in
      CMA, and the AMA, or both should remain automatic.The House requested an ad hoc
      committee to cause a "poll and its attendant statements to be developed by May 21
      for copy distribution to component medical societies and printing in the CMA
      membership news media-with mailing of the official questionnaires to the society
      members on September 1, 1971." Members will be asked to express their opinions by
      ballot in September.The Speaker of the House appointed an ad hoc committee of the
      House to conduct this informed opinion poll of the membership. The committee has
      met to set ground rules, prepare accurate pro and con statements and write the
      poll questions-in accord with the directions of the House action.The Informed
      Membership Opinion Poll Committee, with the advice of Decision Making
      Information, Inc., an independent consultant, prepared statements regarding
      unified and separate membership in CMA and AMA from comments which were solicited
      from every county medical society. A statement by legal counsel for the
      California Medical Association on the structural relationship of AMA, CMA and
      component societies, and the statements on unified or separate membership
      prepared by the committee appear on the following two pages.

PMID- 18730551
TI  - Pharmacist and the physician.

PMID- 18730550
TI  - Report on student participation in organized medicine.

PMID- 18730552
TI  - A new circumcision device-a preliminary report.

PMID- 18730554
TI  - Epitomes of progress -- radiology.

PMID- 18730553
TI  - Role of Laparotomy in Staging of Hodgkin's Disease.

PMID- 18730555
TI  - Disseminated multiple pulmonary calcifications due to coccidioidomycosis.

PMID- 18730556
TI  - Multiple pulmonary fibroleiomyomatous hamartomas.

PMID- 18730557
TI  - Pitfalls in post-herniorrhaphy diagnosis of gastric lesions.

PMID- 18730559
TI  - Superior marginal rib defects.

PMID- 18730558
TI  - Hysterography in the detection of hydatidiform mole.

PMID- 18730560
TI  - Food-barium meal of value in diagnosing gastric outlet obstruction.

PMID- 18730561
TI  - Percutaneous needle biopsy of pulmonary lesions for cell culture.

PMID- 18730562
TI  - Emergency treatment of pneumothorax.

PMID- 18730563
TI  - Angiographic demonstration of renal vein invasion in renal carcinoma.

PMID- 18730564
TI  - Treatment of retinoblastoma.

PMID- 18730565
TI  - Selective arterial infusions of vasoconstricting agents in the control of
      gastrointestinal hemorrhage.

PMID- 18730566
TI  - New techniques in pulmonary angiography.

PMID- 18730567
TI  - Transfemoral selective coronary arteriography.

PMID- 18730569
TI  - Radionuclide studies as a guide to status of the renal transplant.

PMID- 18730568
TI  - Radionuclide Detection of Left-to-Right Cardiac Shunts.

PMID- 18730570
TI  - Radionuclide spleen scans.

PMID- 18730571
TI  - Ultrasonic cardiovascular diagnosis.

PMID- 18730572
TI  - Abdominal echography.

PMID- 18730574
TI  - Bone Scanning in the Pre-treatment and Follow-up of Malignant Disease.

PMID- 18730573
TI  - Radiation dosage and the "rad equivalent therapy".

PMID- 18730576
TI  - United or separate?

PMID- 18730575
TI  - Angiography of pediatric abdominal masses.

PMID- 18730577
TI  - Dealing in Futures-Part II: In Democratic Societies.

PMID- 18730578
TI  - Venereal disease epidemic.

PMID- 18730579
TI  - A happy choice.

PMID- 18730580
TI  - The AMA Convention-A Report on Activities by the CMA Delegation.

PMID- 18730581
TI  - Shall organized medicine be unified, or separate?
AB  - MEMBERS OF THE CALIFORNIA MEDICAL ASSOCIATION ARE TO BE CALLED UPON IN SEPTEMBER
      TO BALLOT ON A QUESTION OF GREAT IMPORTANCE TO THE FUTURE OF ORGANIZED MEDICINE:
      Shall membership in organized medicine-county medical society, California Medical
      Association, American Medical Association-be unified, or shall such membership be
      separate?In the July issue we published statements pro and con which the Informed
      Membership Poll Committee had prepared from statements of position on both sides
      of the question that the committee had solicited from county societies and
      individuals.Here, for the fuller information of our readers on this momentous
      question, we are presenting material representative of the arguments that the
      Committee digested in the statements printed in the July issue.

PMID- 18730582
TI  - Training groups, encounter groups, sensitivity groups and group psychotherapy.
AB  - Descriptions and comparison of group therapies and the new group procedures
      (training groups and sensitivity groups-an outgrowth of the so-called Laboratory
      Movement methods of the mid-1930's) have been provided for the better
      understanding of non-psychiatric physicians. A group leader must have proper
      training and must help his group in its search for its avowed goals, whether he
      is a group therapist, a sensitivity trainer, or anyone else interested in
      utilizing group processes.Those goals are either the therapeutic benefit of the
      individual, as defined in group psychotherapy, or a better understanding of how
      one functions in groups, as in T-groups or the other group processes in the area
      of sensitive living. All group situations contain powerful tools which must be
      handled with proper respect. When so handled by experienced leaders, the
      individuals involved can achieve their goals in these group experiences.

PMID- 18730583
TI  - The selective service system and physicians.

PMID- 18730584
TI  - Soft contact lenses.

PMID- 18730585
TI  - Psychiatry.

PMID- 18730586
TI  - Epitomes of progress -- psychiatry and neurology.

PMID- 18730587
TI  - School phobia: controlled imipramine treatment.

PMID- 18730588
TI  - Abortion-psychiatric implication.

PMID- 18730589
TI  - Sex education in medicine.

PMID- 18730590
TI  - The hyperactive child.

PMID- 18730591
TI  - Alcoholism: contemporary attitudes.

PMID- 18730592
TI  - Electrosleep therapy: current usage in psychiatry.

PMID- 18730593
TI  - The psychophysiology of sleep.

PMID- 18730594
TI  - Biofeedback training in voluntary control of EEG alpha rhythms.

PMID- 18730595
TI  - Megavitamins in schizophrenia.

PMID- 18730596
TI  - The second year of life.

PMID- 18730597
TI  - Recent developments in the prevention of mental retardation.

PMID- 18730598
TI  - Narcolepsy and cataplexy-innovations in diagnosis.

PMID- 18730599
TI  - Cerebral evoked potentials in schizophrenia.

PMID- 18730600
TI  - Evoked cortical potentials in hyperkinetic children.

PMID- 18730601
TI  - Contemporary psychoanalysis.

PMID- 18730602
TI  - Normal pressure hydrocephalus.

PMID- 18730603
TI  - Treatment of cerebral edema.

PMID- 18730604
TI  - Brain death.

PMID- 18730605
TI  - Neurology: prenatal diagnosis of inherited neurologic diseases.

PMID- 18730606
TI  - Prophylaxis of vascular headaches.

PMID- 18730607
TI  - The neurology of drug abuse.

PMID- 18730608
TI  - Treatment of febrile seizures.

PMID- 18730609
TI  - Cervical spondylosis-the overlooked cause of impaired gait.

PMID- 18730610
TI  - Muscle biopsy in the diagnosis of neuromuscular disease.

PMID- 18730611
TI  - Medical treatment of trigeminal neuralgia.

PMID- 18730612
TI  - Current areas of investigation on the medical management of stroke.

PMID- 18730613
TI  - Detection of the muscular dystrophy carrier.

PMID- 18730615
TI  - Electrodiagnostic studies in neuromuscular disease.

PMID- 18730614
TI  - Usefulness of brain scanning.

PMID- 18730616
TI  - Serum enzymes in the diagnosis of neuromuscular disorders.

PMID- 18730617
TI  - Facial Nerve Excitability Tests and Prognosis in Bell's Palsy.

PMID- 18730619
TI  - The biologic premise.

PMID- 18730618
TI  - OX, NO, PAN and SO-When and How Are They Toxic?

PMID- 18730620
TI  - Acute renal failure: prevention, prophylaxis and progress.

PMID- 18730621
TI  - Dealing in Futures-Part III: Planning in CMA.

PMID- 18730622
TI  - A Hot Word from #AB 3,522,477.

PMID- 18730623
TI  - DOA for the AMA and CMA.

PMID- 18730625
TI  - Lung disease from contaminated air coolers.

PMID- 18730624
TI  - Air pollution, health effects and urban growth.

PMID- 18730626
TI  - Epitomes of progress -- allergy.

PMID- 18730628
TI  - Bee sting allergy.

PMID- 18730627
TI  - Enzyme-containing detergents as a cause of allergic disease.

PMID- 18730629
TI  - Mites in house dust.

PMID- 18730630
TI  - Association of air pollution with asthma.

PMID- 18730631
TI  - Insulin allergy.

PMID- 18730632
TI  - Allergy and serous otitis media.

PMID- 18730633
TI  - Air cleaning filters and inhalant allergy.

PMID- 18730634
TI  - Alpha-1 antitrypsin deficiency.

PMID- 18730635
TI  - Current Status of Immunoglobulin E (IgE).

PMID- 18730636
TI  - Disodium cromoglycate in the treatment of bronchial asthma-further clinical
      trials.

PMID- 18730637
TI  - Nose drop habituation.

PMID- 18730638
TI  - The familial nature of milk allergy.

PMID- 18730639
TI  - Doubtful correlation between asthma and worms.

PMID- 18730640
TI  - Clinical use of transfer factor.

PMID- 18730642
TI  - College health services.

PMID- 18730641
TI  - Excessive use of symphathomimetic nebulizers in asthma.

PMID- 18730643
TI  - Coronary arteriography: where? When?

PMID- 18730644
TI  - Medical education in transformation.

PMID- 18730645
TI  - The health care team.

PMID- 18730646
TI  - The watts health miracle.

PMID- 18730647
TI  - Conserving California's Water.

PMID- 18730648
TI  - Proposed cma constitutional amendments for action in 1972.

PMID- 18730650
TI  - Epitomes of progress -- general and family practice.

PMID- 18730649
TI  - Extracorporeal Circulation-Part II.

PMID- 18730651
TI  - Drug exposure in the hospital.

PMID- 18730653
TI  - Triiodothyronine.

PMID- 18730652
TI  - Coronary risk in post-menopausal women.

PMID- 18730654
TI  - Skillful neglect.

PMID- 18730655
TI  - Use and abuse of sedatives.

PMID- 18730656
TI  - Some implications of zero population growth.

PMID- 18730657
TI  - The pill and the teenage girl.

PMID- 18730658
TI  - Risk of breast cancer.

PMID- 18730659
TI  - Hippie hepatitis.

PMID- 18730660
TI  - Incidental hypokalemia in ambulatory patients.

PMID- 18730661
TI  - Epidemic gonorrhea.

PMID- 18730662
TI  - Increasing problem of malaria.

PMID- 18730664
TI  - The use of packed red cells in transfusions.

PMID- 18730663
TI  - Learning and behavior disorders in children.

PMID- 18730666
TI  - The 101st scientific assembly.

PMID- 18730665
TI  - National health insurance-caveat emptor.

PMID- 18730667
TI  - CBS/CMA Relationships.

PMID- 18730668
TI  - Epitomes of progress -- plastic surgery.

PMID- 18730669
TI  - More physicians through perimeter personnel training.

PMID- 18730670
TI  - Dermatologic radiotherapy-R.I.p.

PMID- 18730671
TI  - No dearth of opportunity.

PMID- 18730672
TI  - Peripheral venous diseases.

PMID- 18730673
TI  - Selected items from the FDA bulletin-october 1971.

PMID- 18730674
TI  - Sudden infant death syndrome.

PMID- 18730675
TI  - Rabies.

PMID- 18730676
TI  - Epitomes of progress -- preventive medicine and public health.

PMID- 18730677
TI  - Methyl mercury.

PMID- 18730678
TI  - Isolation techniques for use in hospitals.

PMID- 18730679
TI  - Chemoprophylaxis for malaria.

PMID- 18730680
TI  - Tetanus prevention.

PMID- 18730681
TI  - Australia antigen and viral hepatitis.

PMID- 18730682
TI  - The diagnosis and management of hyperlipidemia.

PMID- 18730683
TI  - Treatment of mild hypertension.

PMID- 18730684
TI  - Malaria.

PMID- 18730685
TI  - Pregnancy testing.

PMID- 18730686
TI  - Syphilis and gonorrhea therapy.

PMID- 18730687
TI  - Current street language for various drugs that are abused.

PMID- 18730688
TI  - Cost accounting health care.

PMID- 18730689
TI  - Methadone treatment of opiate addiction.

PMID- 18730690
TI  - CMERF-How You Can Support It.

PMID- 18730691
TI  - Medical care, health care, and the social scene: a mini-symposium.

PMID- 18730692
TI  - Medical care, health care, and the social scene a mini-symposium: a mini
      symposium.

PMID- 18730694
TI  - Coronary arteriography.

PMID- 18730693
TI  - Medical care, health care, and the social scene: a mini-symposium.

PMID- 18730695
TI  - An unexpected protest.

PMID- 18730696
TI  - Diethylstilbestrol: problems of unusual drug dosage and administration.

PMID- 18730697
TI  - Selected item from the FDA drug bulletin-november 1971: diethylstilbestrol
      contraindicated in pregnancy.

PMID- 18730698
TI  - Epitomes of progress -- general surgery.

PMID- 18730699
TI  - Selective gastric vagotomy.

PMID- 18730700
TI  - Mediastinoscopy in patients with cancer of the lung.

PMID- 18730701
TI  - Intestinal bypass for morbid obesity.

PMID- 18730702
TI  - Antibacterial agents to control infection associated with burns.

PMID- 18730703
TI  - Aggressive approach to diagnosis of lung infiltrates in the compromised host.

PMID- 18730704
TI  - Lymphocyte tissue culture in transplant surgery.

PMID- 18730705
TI  - Zollinger-Ellison Syndrome (ZES).

PMID- 18730706
TI  - The role of parathyroidectomy in secondary hyperparathyroidism.

PMID- 18730707
TI  - Management of liver injuries.

PMID- 18730709
TI  - Use of the water bed.

PMID- 18730708
TI  - "The liberated sex"-catchy, or pejorative?

PMID- 18730710
TI  - Equal opportunity.

PMID- 18730711
TI  - Doppler monitoring.

PMID- 18730712
TI  - Epitomes of progress -- obstetrics and gynecology.

PMID- 18730713
TI  - A trend to be reversed.

PMID- 18730714
TI  - Comments on traffic medicine.

PMID- 18730716
TI  - Comments on traffic medicine.

PMID- 18730715
TI  - Comments on traffic medicine.

PMID- 18730717
TI  - Comments on traffic medicine.

PMID- 18730719
TI  - It's Blood-Not Soup.

PMID- 18730718
TI  - Methadone is Controversial.

PMID- 18730720
TI  - An ethical issue.

PMID- 18730721
TI  - Rising Cost of PG Study.

PMID- 18730722
TI  - Small intestinal biopsies.

PMID- 18730723
TI  - Epitomes of progress -- pathology.

PMID- 18730724
TI  - Role of properdin in kidney diseases.

PMID- 18730725
TI  - Significance of mitochondrial antibody test.

PMID- 18730726
TI  - Molecular basis for a simple, specific test for s hemoglobin: the murayama test
      and desickling of sickle cells with urea.

PMID- 18730727
TI  - Significance of smooth muscle antibodies in liver disease.

PMID- 18730728
TI  - Value of histochemistry in the investigation of human muscle diseases.

PMID- 18730729
TI  - Prenatal diagnosis of inherited diseases.

PMID- 18730731
TI  - Status of C type virus in cat tumors.

PMID- 18730730
TI  - Evaluation of hepatotoxicity by electron microscopy.

PMID- 18730732
TI  - Lymphomatoid granulomatosis.

PMID- 18730733
TI  - Microangiopathic hemolytic anemia.

PMID- 18730734
TI  - Pulmonary veno-obstructive disease.

PMID- 18730735
TI  - Platelet transfusions.

PMID- 18730736
TI  - Platelet storage.

PMID- 18730738
TI  - Who is to decide and who is to pay.

PMID- 18730737
TI  - Reed-Sternberg Cells in Non-Hodgkin's Disease.

PMID- 18730740
TI  - This also for the ears.

PMID- 18730739
TI  - A trial balloon.

PMID- 18730742
TI  - Epitomes of progress -- dermatology.

PMID- 18730741
TI  - Special phones for the handicapped.

PMID- 18730743
TI  - Treatment of superficial malignancies with topical 5-Fluorouracil.

PMID- 18730744
TI  - Cold urticaria.

PMID- 18730745
TI  - The genetics of psoriasis.

PMID- 18730746
TI  - Complications of topical steroid therapy.

PMID- 18730747
TI  - Erythrohepatic protoporphyria.

PMID- 18730748
TI  - Cutaneous complications of tetracycline therapy.

PMID- 18730749
TI  - Foods and acne.

PMID- 18730750
TI  - Sunscreens.

PMID- 18730751
TI  - Topical urea.

PMID- 18730752
TI  - Dermatophyte test medium.

PMID- 18730753
TI  - Staphylococcal scalded skin syndrome.

PMID- 18730754
TI  - Phenolic depigmentation of skin.

PMID- 18730755
TI  - Skin manifestations of drug addiction.

PMID- 18730756
TI  - Preservatives as sensitizers.

PMID- 18730758
TI  - Photodynamic inactivation of herpes simplex infections.

PMID- 18730757
TI  - Aphthous stomatitis.

PMID- 18730759
TI  - Topical vitamin a Acid.

PMID- 18730760
TI  - Psoralens and cutaneous photosensitization.

PMID- 18730761
TI  - A time for renewal.

PMID- 18730762
TI  - The zollinger-ellison syndrome.

PMID- 18730763
TI  - Intestinal disaccharidase deficiencies-implication for the '70s.

PMID- 18730764
TI  - Getting quality into place.

PMID- 18730765
TI  - CMA Priorities and Communications.

PMID- 18730766
TI  - CMA Looks Ahead: Approaching the Time for Decision The Hard Choices Facing
      American Medicine.

PMID- 18730767
TI  - Help from Helpmates: With It with the CMA Auxiliary.

PMID- 18730768
TI  - Current patterns of drug misuse.

PMID- 18730769
TI  - Epitomes of progress -- psychiatry.

PMID- 18730770
TI  - Mental health of american indians.

PMID- 18730771
TI  - Black physicians and black clients-is it "a family affair"?

PMID- 18730772
TI  - Wrist slashers.

PMID- 18730773
TI  - Psychoanalysts view aggression.

PMID- 18730775
TI  - The lateral specialization of the human brain for cognition; EEG and lateral eye
      movement studies.

PMID- 18730774
TI  - Psychiatric emergency services.

PMID- 18730776
TI  - Newer approaches to drug abuse.

PMID- 18730777
TI  - Behavior therapy.

PMID- 18730778
TI  - Short versus long hospital treatment of schizophrenia.

PMID- 18730779
TI  - Genetics of human violence.

PMID- 18730780
TI  - Current approaches to the study of suicide prevention.

PMID- 18730781
TI  - Ultradian rhythms and behavior.

PMID- 18730782
TI  - Encounter groups.

PMID- 18730783
TI  - Society needs its physicians and vice versa.

PMID- 18730784
TI  - No-fault insurance in medicine.

PMID- 18730785
TI  - More on methadone maintenance.

PMID- 18730786
TI  - Smoking in hospitals.

PMID- 18730787
TI  - Free clinics.

PMID- 18730788
TI  - In defense of corticosteroids.

PMID- 18730790
TI  - Injection neuropathy.

PMID- 18730789
TI  - Unwilling smoking.

PMID- 18730791
TI  - Chronic hemodialysis in california.

PMID- 18730792
TI  - Clinical cardiology: the stokes-adams syndrome-definition and etiology;
      mechanisms and treatment.

PMID- 18730793
TI  - Selected items from the FDA drug bulletin-february and may, 1972.

PMID- 18730794
TI  - Epitomes of progress -- pediatrics.

PMID- 18730795
TI  - Salt poisoning from saline emetics.

PMID- 18730796
TI  - Interhospital infant transport.

PMID- 18730797
TI  - Triple vaccine.

PMID- 18730798
TI  - Recognition of serum hepatitis.

PMID- 18730799
TI  - Current dietary hazards.

PMID- 18730800
TI  - Evaluation for possible immunologic deficiency disorders.

PMID- 18730801
TI  - Assessment of the risk of the respiratory distress syndrome with preterm
      delivery.

PMID- 18730802
TI  - The return of the scabies mite.

PMID- 18730803
TI  - Medium chain triglycerides in pediatric practice.

PMID- 18730804
TI  - Immunosuppressive therapy of renal disease.

PMID- 18730805
TI  - The hexachlorophene controversy.

PMID- 18730806
TI  - Irrationalities in health care delivery.

PMID- 18730808
TI  - Maternal death due to uterine hemorrhage.

PMID- 18730807
TI  - Pancreatitis, the Gastroenterologist's (and Everyone Else's) Enigma.

PMID- 18730809
TI  - Three political philosophies and medical care.

PMID- 18730810
TI  - On Healing the HCDS.

PMID- 18730811
TI  - A new approach (optics) in oto-rhino-laryngology.

PMID- 18730813
TI  - The use and management of cuffed endotracheal tubes.

PMID- 18730812
TI  - Epitomes of progress -- otolaryngology.

PMID- 18730814
TI  - Sudden sensorineural hearing loss.

PMID- 18730815
TI  - Posterior sinus approach for nosebleeds.

PMID- 18730816
TI  - Vertigo in "whiplash injuries".

PMID- 18730818
TI  - Hearing AIDS and the pre-school child.

PMID- 18730817
TI  - Cryosurgery in otolaryngology.

PMID- 18730819
TI  - Conservation surgery of the larynx.

PMID- 18730820
TI  - Audiologic evaluation in newborns.

PMID- 18730821
TI  - Microscopic laryngoscopy.

PMID- 18730822
TI  - Rhinoplasty.

PMID- 18730823
TI  - Laryngeal edema and corticosteroid therapy.

PMID- 18730825
TI  - A proposition for the health sciences.

PMID- 18730824
TI  - Management and treatment of the neck mass with the unknown primary.

PMID- 18730826
TI  - Another view of no-fault insurance.

PMID- 18730827
TI  - Health education.

PMID- 18730828
TI  - Microwave and man.

PMID- 18730829
TI  - Muscle relaxants.

PMID- 18730830
TI  - Recent advances in obstetric anesthesia.

PMID- 18730831
TI  - Halogenated anesthetic agents.

PMID- 18730832
TI  - Dissociative anesthesia.

PMID- 18730834
TI  - New halogenated anesthetics: enflurane and isoflurane.

PMID- 18730833
TI  - Patient monitoring.

PMID- 18730835
TI  - Local anesthetics and regional anesthesia.

PMID- 18730836
TI  - Psychedelic drugs and anesthesia.

PMID- 18730837
TI  - Emergency outpatient anesthesia.

PMID- 18730838
TI  - Anesthesia for intracranial operation.

PMID- 18730839
TI  - Pediatric anesthesia.

PMID- 18730840
TI  - Recent advances in respiratory therapy.

PMID- 18730842
TI  - Proposition two-health sciences facilities.

PMID- 18730841
TI  - The health sciences bond issue.

PMID- 18730843
TI  - Proposed CMA Constitutional Amendments.

PMID- 18730844
TI  - Epitomes of progress -- neurology.

PMID- 18730845
TI  - Bloody tap and yellow peril.

PMID- 18730846
TI  - Subacute sclerosing panencephalitis.

PMID- 18730848
TI  - Alpha rhythms and what they mean.

PMID- 18730847
TI  - Current trends in L-dopa therapy of parkinsonism.

PMID- 18730849
TI  - Myasthenia gravis.

PMID- 18730850
TI  - Treatment of multiple sclerosis.

PMID- 18730851
TI  - The Use of AMICAR(R) in Subarachnoid Hemorrhage.

PMID- 18730852
TI  - New diagnostic and treatment techniques in cryptococcal meningitis.

PMID- 18730854
TI  - Headache and "the pill".

PMID- 18730853
TI  - The medical treatment of epilepsy.

PMID- 18730855
TI  - Propranolol in neurology.

PMID- 18730856
TI  - Ampac-calpac.

PMID- 18730857
TI  - One rx at a time.

PMID- 18730858
TI  - An answer to a call for help.

PMID- 18730860
TI  - Epitomes of progress -- radiology.

PMID- 18730859
TI  - Health insurance payments.

PMID- 18730861
TI  - Indications and value of coronary arteriography.

PMID- 18730862
TI  - Coronary arteriography in acute myocardial infarction.

PMID- 18730863
TI  - Efficacy studies: skull radiography in head trauma.

PMID- 18730864
TI  - Asbestosis-diaphragmatic pleural calcification.

PMID- 18730865
TI  - Physiology and significance of the prolonged nephrogram.

PMID- 18730866
TI  - Hodgkin's Lymphomas Revisited.

PMID- 18730867
TI  - Diagnostic ultrasound in the diagnosis of renal masses.

PMID- 18730868
TI  - Hypertension caused by constricting renal lesions ("page kidney").

PMID- 18730869
TI  - Vascular changes associated with drug abuse.

PMID- 18730870
TI  - Non-operative retained biliary tract stone extraction.

PMID- 18730871
TI  - The role of lymphangiography in ovarian, cervical, endometrial and prostatic
      cancer.

PMID- 18730872
TI  - The angiographic diagnosis of gastrointestinal bleeding.

PMID- 18730873
TI  - A refreshing approach.

PMID- 18730874
TI  - Proposed CMA Constitutional Amendments.

PMID- 18730875
TI  - Hydrophilic "soft" contact lenses.

PMID- 18730877
TI  - Microsurgery in open angle glaucoma.

PMID- 18730876
TI  - Epitomes of progress -- ophthalmology.

PMID- 18730878
TI  - Management of congenital cataracts.

PMID- 18730879
TI  - Blow-out Fractures of the Orbital Floor.

PMID- 18730880
TI  - Diabetic retinopathy.

PMID- 18730882
TI  - Desferrioxamine B in treatment of ocular foreign bodies.

PMID- 18730881
TI  - Strabismus management.

PMID- 18730883
TI  - Rhabdomyosarcoma of the orbit.

PMID- 18730884
TI  - Prophylaxis in cataract surgery.

PMID- 18730885
TI  - Ultrasonic applications in ocular trauma.

PMID- 18730886
TI  - Weinberger to HEW.

PMID- 18730887
TI  - The CALPAC Record.

PMID- 18730889
TI  - Of drugs and races.

PMID- 18730888
TI  - The meaning of dysmature.

PMID- 18730890
TI  - Epitomes of progress-allergy.

PMID- 18730892
TI  - Clinical uses of transfer factor.

PMID- 18730891
TI  - The new Beta stimulators-better as well as newer?

PMID- 18730893
TI  - Modifications of antigens used in immunotherapy.

PMID- 18730894
TI  - Newer mediators in allergic diseases.

PMID- 18730895
TI  - Inhibition of histamine release by cyclic 3', 5'-adenosine monophosphate (cAMP).

PMID- 18730896
TI  - Status of testing for penicillin allergy.

PMID- 18730897
TI  - Current status of provocative food testing.

PMID- 18730898
TI  - Pitfalls in the use of skin testing in allergy.

PMID- 18730899
TI  - Bronchiolitis-a stage of incipient bronchial asthma?

PMID- 18730901
TI  - Of racial minorities in medical education.

PMID- 18730900
TI  - A Critical Appraisal of Recent in vitro Diagnostic Tests for Allergy.

PMID- 18730902
TI  - Housestaff membership merger for the future.

PMID- 18730903
TI  - Illicit intravenous drug use and bacterial endocarditis.

PMID- 18730904
TI  - Prolactin.

PMID- 18730905
TI  - Responses to "a call for help".

PMID- 18730906
TI  - Actinobacillus actinomycetemcomitans.

PMID- 18730907
TI  - A question of significance.

PMID- 18730908
TI  - Minority enrollment programs of california medical schools.

PMID- 18730910
TI  - Epitomes of progress-orthopedics.

PMID- 18730909
TI  - A membership program for residents and interns: a report to the council by the
      commission on communications.

PMID- 18730911
TI  - Sickle cell disease in orthopedics.

PMID- 18730912
TI  - Fasciotomy for swollen limbs.

PMID- 18730913
TI  - Knee-joint replacement.

PMID- 18730914
TI  - Current treatment of myelodysplasia.

PMID- 18730915
TI  - Inheritance of idiopathic scoliosis.

PMID- 18730916
TI  - Congenital hip dysplasia.

PMID- 18730917
TI  - Present status of anterior interbody fusion in treatment of disorders of the
      lumbar spine.

PMID- 18730918
TI  - Little league elbow.

PMID- 18730919
TI  - Immediate treatment of spinal cord injuries.

PMID- 18730920
TI  - Chymopapain chemonucleolysis.

PMID- 18730921
TI  - Hand and foot problems in drug users.

PMID- 18730922
TI  - Arthroscopy of the knee.

PMID- 18730924
TI  - On the responsibility and authority of physicians.

PMID- 18730923
TI  - Controversial ethical issues in medicine.

PMID- 18730925
TI  - Mesenteric vascular insufficiency.

PMID- 18730926
TI  - Drug dosage for allergic rhinitis.

PMID- 18730927
TI  - More on abortion.

PMID- 18730928
TI  - Diarrhea in the morning.

PMID- 18730929
TI  - Letters to the editor.

PMID- 18730930
TI  - Letters to the editor.

PMID- 18730932
TI  - Toward unity and renewal.

PMID- 18730931
TI  - The heart surgeon.

PMID- 18730933
TI  - Physician involvement in health care planning.

PMID- 18730934
TI  - COMMUNITY MEDICINE IN CALIFORNIA-A Symposium.

PMID- 18730935
TI  - Epitomes of progress-preventive medicine and public health.

PMID- 18730936
TI  - California moves for control of salmonellosis associated with pet turtles.

PMID- 18730938
TI  - Vibrio Parahemolyticus, a Newly Recognized Cause of Food-borne Illiness.

PMID- 18730937
TI  - Interpreting current serologic tests for syphilis.

PMID- 18730939
TI  - Zoster Immune Globulin (ZIG).

PMID- 18730940
TI  - Herpesvirus infections and cancer of the cervix.

PMID- 18730941
TI  - Primary amebic meningoencephalitis.

PMID- 18730942
TI  - Mumps vaccine.

PMID- 18730943
TI  - The rise and fall of botulism.

PMID- 18730944
TI  - Toward greater unity and greater strength.

PMID- 18730945
TI  - Treatment of streptococcal pharyngitis by clinical criteria.

PMID- 18730946
TI  - Epitomes of progress-general and family practice.

PMID- 18730947
TI  - Office dilatation and curettage.

PMID- 18730948
TI  - Pain in Viral vs. Bacterial Pharyngitis.

PMID- 18730949
TI  - Minor tranquilizers-how minor are they?

PMID- 18730950
TI  - Cryocautery in the office treatment of chronic cervicitis.

PMID- 18730951
TI  - Can the diaphragm make a comeback?

PMID- 18730952
TI  - Prophylaxis of migraine using propranolol.

PMID- 18730953
TI  - Hypothyroidism-do we finally have a single test?

PMID- 18730954
TI  - Lactase deficiency, geriatric and ethnic considerations.

PMID- 18730955
TI  - Where we stand on drug abuse.

PMID- 18730956
TI  - More on gonorrhea.

PMID- 18730957
TI  - Annual session.

PMID- 18730959
TI  - Epitomes of progress-obstetrics and gynecology.

PMID- 18730958
TI  - Chiropractic and exposure to radiation.

PMID- 18730960
TI  - The hirsute patient.

PMID- 18730961
TI  - Clinical application of genetic detection and counseling.

PMID- 18730963
TI  - Genetic counseling.

PMID- 18730962
TI  - Important advances in paracervical block anesthesia.

PMID- 18730964
TI  - Respiratory distress syndrome: how it can be prevented.

PMID- 18730965
TI  - Current concepts of fetal monitoring.

PMID- 18730966
TI  - Hypothalamic hormones.

PMID- 18730967
TI  - Use of amniotic fluid: assessment of the fetus.

PMID- 18730968
TI  - Serum FSH-LH Determinations in Gynecologic Practice.

PMID- 18730969
TI  - Laminaria tents as an aid for suction abortion.

PMID- 18730970
TI  - Vaginal adenosis.

PMID- 18730971
TI  - Use of estriol levels to permit delivery of frank diabetics at term.

PMID- 18730972
TI  - Herpes genitalis.

PMID- 18730973
TI  - The role of colposcopy in gynecologic practice.

PMID- 18730974
TI  - Progress in epilepsy.

PMID- 18730975
TI  - The price of quality in medical care.

PMID- 18730977
TI  - The medical "generation gap".

PMID- 18730976
TI  - Counseling about sickle cell.

PMID- 18730978
TI  - Epitomes of progress-plastic surgery.

PMID- 18730979
TI  - Plastic operation on the abdomen.

PMID- 18730980
TI  - Reduction mammaplasty.

PMID- 18730981
TI  - Repair of cleft palate with an island flap.

PMID- 18730982
TI  - Atrophy following cortisone injection for hypertrophic scar.

PMID- 18730983
TI  - Maxillo-facial injuries following accident.

PMID- 18730984
TI  - Early orthopedic positioning and bone grafting in treatment of cleft lip and
      palate.

PMID- 18730986
TI  - To heal or to treat?

PMID- 18730985
TI  - On some unproven effects of aspirin and saccharine.

PMID- 18730987
TI  - Selected items from the FDA drug bulletin-may 1973.

PMID- 18730988
TI  - Short stay surgical centers: a statement by the california medical association
      commission on health facilities.

PMID- 18730989
TI  - Epitomes of progress-pathology.

PMID- 18730990
TI  - Inclusion cell disease (I-cell).

PMID- 18730992
TI  - Skeletal scintiphotography and metastatic breast carcinoma.

PMID- 18730991
TI  - Immunoassays for drugs of abuse.

PMID- 18730993
TI  - Cultured skin fibroblasts and their use in genetic counseling.

PMID- 18730994
TI  - Amniocentesis.

PMID- 18730996
TI  - "False positive" fluorescent treponemal antibody-absorption test reactions.

PMID- 18730995
TI  - Human Placental Lactogen (HPL).

PMID- 18730997
TI  - New (but Old) Hazards in Autopsy Pathology.

PMID- 18730998
TI  - Estriol assays to assess fetal status.

PMID- 18730999
TI  - Fibrin split products.

PMID- 18731000
TI  - Carcinoembryonic Antigen (CEA) in Clinical Diagnosis.

PMID- 18731002
TI  - Serum alkaline phosphatase isoenzymes.

PMID- 18731001
TI  - Nitroblue tetrazolium test as evidence of bacterial infection?

PMID- 18731003
TI  - Detection of drug abusers by urine screening.

PMID- 18731004
TI  - Use of packed red blood cells for transfusion.

PMID- 18731005
TI  - Satisfactory care at low cost.

PMID- 18731006
TI  - Can standardized medical care really be humane.

PMID- 18731007
TI  - More on botulism.

PMID- 18731009
TI  - Pinpointing preceptorships.

PMID- 18731008
TI  - Sickle cell trait hematuria.

PMID- 18731010
TI  - Hemolytic disease reporting.

PMID- 18731012
TI  - Epitomes of progress-internal medicine.

PMID- 18731011
TI  - On Throw-aways and Such.

PMID- 18731013
TI  - Ultrasound as a non-invasive technique for measuring cardiac performance and
      diagnosing cardiac lesions.

PMID- 18731014
TI  - Combination drug therapy in metastatic carcinoma of the breast.

PMID- 18731015
TI  - Hypothalamic hypothyroidism.

PMID- 18731016
TI  - Indications for lavage in the treatment of bronchopulmonary disease.

PMID- 18731017
TI  - Alpha(1)-antitrypsin deficiency.

PMID- 18731018
TI  - The significance of australia antigen.

PMID- 18731019
TI  - The use of sulfonylureas in the treatment of adult onset diabetes.

PMID- 18731020
TI  - Some effects of ischemia on heart muscle.

PMID- 18731022
TI  - Human tumor viruses.

PMID- 18731021
TI  - Protamine sulfate test-its role in differentiating disseminated intravascular
      clotting from primary fibrinolysis.

PMID- 18731023
TI  - The significance of triiodothyronine.

PMID- 18731024
TI  - A case for "backlash".

PMID- 18731025
TI  - AMA Placement Service.

PMID- 18731026
TI  - Epitomes of progress-chest diseases.

PMID- 18731027
TI  - Fiberoptic bronchoscopy.

PMID- 18731028
TI  - Cardiovascular function in chronic obstructive lung disease.

PMID- 18731029
TI  - In-hospital use of intermittent positive pressure breathing therapy.

PMID- 18731030
TI  - Flucytosine, a major antifungal agent.

PMID- 18731031
TI  - Alpha(1)-Antitrypsin: What's in It for the Patient?

PMID- 18731032
TI  - Early diagnosis of chronic obstructive pulmonary disease.

PMID- 18731033
TI  - Hypoxemic, Hyperventilatory Respiratory Insufficiency:A Common Post-operative
      Complication.

PMID- 18731034
TI  - Reversed aorta to saphenous vein grafts.

PMID- 18731035
TI  - Corticosteroids in the treatment of adult respiratory distress syndromes.

PMID- 18731036
TI  - Surgical treatment of hiatal hernia.

PMID- 18731037
TI  - Drug therapy in asthma.

PMID- 18731038
TI  - Lung oxidant toxicity.

PMID- 18731039
TI  - From "crisis" to chaos to what?

PMID- 18731040
TI  - Hazards of sound-alike, look-alike drug names.

PMID- 18731041
TI  - Professional competence.

PMID- 18731043
TI  - Special editorial for a special report: enlightened self-interest.

PMID- 18731042
TI  - CONTINUING MEDICAL EDUCATION: A Message from the President.

PMID- 18731044
TI  - TECHNIQUE AND INTERPRETATION OF LOWER EXTREMITY VENOGRAMS.

PMID- 18731046
TI  - MATERNAL, FETAL AND NEONATAL MORTALITY.

PMID- 18731045
TI  - WHAT THE WAR TAUGHT ABOUT AMPUTATIONS.

PMID- 18731048
TI  - EDITORIAL ANNOUNCEMENT.

PMID- 18731047
TI  - PYELITIS OF PREGNANCY.

PMID- 18731049
TI  - Section of the Vagus Nerves in the Treatment of Peptic Ulcer.

PMID- 18731050
TI  - MEDICINE ON THE AIR.

PMID- 18731051
TI  - HYPOPARATHYROIDISM.

PMID- 18731052
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731053
TI  - In Memoriam.

PMID- 18731055
TI  - INFORMATION: SICKNESS UNEMPLOYMENT BENEFITS.

PMID- 18731054
TI  - MEDICAL JURISPRUDENCE.

PMID- 18731056
TI  - LIFE-LONG POSTVACCINAL IMMUNITY.

PMID- 18731057
TI  - USE OF THE ANTI-COAGULANTS, HEPARIN AND DICUMAROL.

PMID- 18731058
TI  - PREPAYMENT AND THE FUTURE OF AMERICAN MEDICINE.

PMID- 18731059
TI  - MEDICAL JURISPRUDENCE.

PMID- 18731060
TI  - DEMEROL ANALGESIA IN OBSTETRICS.

PMID- 18731061
TI  - TREATMENT OF THROMBO-EMBOLISM BY VEIN INTERRUPTION.

PMID- 18731062
TI  - THE COCCIDIOIDIN SKIN TEST IN THE PANAMA CANAL ZONE: RESULTS OF A BRIEF SURVEY IN
      TUBERCULOUS AND NON-TUBERCULOUS PATIENTS.

PMID- 18731064
TI  - CALIFORNIA PUBLIC HEALTH LABORATORIES AND THEIR SERVICES.

PMID- 18731063
TI  - POLIOMYELITIS IN SAN FRANCISCO.

PMID- 18731065
TI  - NEWER METHODS IN CONTROL OF RODENT AND INSECT PESTS.

PMID- 18731066
TI  - MALPRACTICE LITIGATION AS IT CONCERNS THE DERMATOLOGIST.

PMID- 18731067
TI  - PURIFIED GLYCOSIDES OF DIGITALIS.

PMID- 18731068
TI  - The A.M.A. and the Future.

PMID- 18731069
TI  - The Laboratory in Medicine and Public Health.

PMID- 18731070
TI  - Cash Sickness Indemnities.

PMID- 18731071
TI  - MEDICAL PROGRESS: Current Methods for Study and Treatment of Sterility.

PMID- 18731072
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731073
TI  - INFORMATION: The Physician and Medical-Legal Phases of Child Adoption.

PMID- 18731074
TI  - MILK-BORNE CARCINOGENIC VIRUS.

PMID- 18731075
TI  - PROTEIN-REPLETION THERAPY.

PMID- 18731076
TI  - USE OF PENICILLIN IN NON-GONOCOCCAL INFECTIONS OF UROGENITAL TRACT.

PMID- 18731077
TI  - THE TREND OF MEDICINE AND ITS RELATIONSHIP TO PREVENTION OF DISEASE.

PMID- 18731079
TI  - DELAYED REACTIONS FOLLOWING PENICILLIN THERAPY: PRELIMINARY REPORT.

PMID- 18731078
TI  - THE CLOTTING MECHANISM AND TESTS FOR ITS EFFICIENCY.

PMID- 18731080
TI  - Can We Predict the Therapeutic Effect of the New Radioactive Elements?

PMID- 18731081
TI  - FREEDOM FROM DOUBT.

PMID- 18731083
TI  - Study of Child Health Services.

PMID- 18731082
TI  - The Responsibility of the Physician in Premarital Examinations.

PMID- 18731084
TI  - THE VETERANS' CHOICE.

PMID- 18731086
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731085
TI  - MEDICAL PROGRESS: The Rh Factor in Clinical Obstetrics.

PMID- 18731088
TI  - Court Holds C.P.S. Not Subject to Insurance Laws.

PMID- 18731087
TI  - In Memoriam.

PMID- 18731089
TI  - Clinical Laboratory Technicians Must Be Licensed.

PMID- 18731090
TI  - IRON SALTS VS. PLUMBISM.

PMID- 18731091
TI  - CONTRADICTORY TERMINOLOGY IN OBSTETRICS.

PMID- 18731093
TI  - MEDICAL JURISPRUDENCE: MALPRACTICE: SUFFICIENCY OF EVIDENCE: DEGREE OF SKILL
      REQUIRED OF A PHYSICIAN.

PMID- 18731092
TI  - ANTI-ALLERGIC "BLOCKADE".

PMID- 18731094
TI  - ANESTHESIA FOR EMERGENCY SURGICAL PROCEDURES.

PMID- 18731095
TI  - TREATMENT OF BLADDER TUMORS.

PMID- 18731096
TI  - THE ONSET OF OVULATION DURING THE PUERPERIUM.

PMID- 18731097
TI  - HUMAN REACTIONS TO EXPERIMENTALLY INDUCED IMPACT FORCES.

PMID- 18731098
TI  - DERMATOLOGICAL ASPECTS OF DERMATITIS DUE TO ATABRINE.

PMID- 18731099
TI  - ATABRINE DERMATITIS AND ASSOCIATED APLASTIC ANEMIA.

PMID- 18731100
TI  - UNTOWARD EFFECTS OF ATABRINE.

PMID- 18731101
TI  - OBSERVATIONS ON THE FUNCTION OF THE CLAVICLE.

PMID- 18731103
TI  - THE RESPONSIBILITY OF THE PEDIATRICIAN IN THE ORTHODONTIC PROBLEM.

PMID- 18731102
TI  - TWO TEAM ABDOMINOPERINEAL RESECTION.

PMID- 18731105
TI  - STREPTOMYCIN.

PMID- 18731104
TI  - MEDICAL PROGRESS: PRESENT CONCEPTS OF THE CLINICAL SIGNIFICANCE OF UNIPOLAR
      PRECORDIAL ELECTROCARDIOGRAMS.

PMID- 18731106
TI  - New Hospitals-New Methods.

PMID- 18731107
TI  - FOLIC ACID.

PMID- 18731108
TI  - CALIFORNIA MEDICAL ASSOCIATION: CALIFORNIA PHYSICIANS' SERVICE-RECORD-KEEPING.

PMID- 18731109
TI  - In Memoriam.

PMID- 18731110
TI  - INFORMATION: STEPS IN BUYING WAR SURPLUS MEDICAL EQUIPMENT.

PMID- 18731112
TI  - CRYSTALLIZATION OF BACTERIAL TOXINS.

PMID- 18731111
TI  - THE ARMY MEDICAL LIBRARY.

PMID- 18731113
TI  - MEDICAL JURISPRUDENCE: INTERPRETATION OF THE BUSINESS AND PROFESSIONS CODE
      PERTAINING TO A HEARING FOR REINSTATEMENT OF A DOCTOR WHOSE LICENSE HAS BEEN
      REVOKED.

PMID- 18731114
TI  - ANALYSIS OF 402 CASES OF CARCINOMA OF THE BREAST.

PMID- 18731115
TI  - DIAGNOSTIC PROBLEMS IN LUETIC CARDIOVASCULAR DISEASE.

PMID- 18731116
TI  - PHYSIOLOGY OF TRAUMATIC REFLEXES AND RESPIRATION DURING ANESTHESIA: OBSERVATIONS
      MADE UNDER PENTOTHAL AND LOCAL NERVE BLOCK.

PMID- 18731117
TI  - TREATMENT OF ACUTE THROAT INFECTIONS, WITH SPECIAL REFERENCE TO THE USE OF
      PENICILLIN.

PMID- 18731118
TI  - TRENDS IN THE AGE DISTRIBUTION OF CHILDHOOD DISEASES.

PMID- 18731119
TI  - METHANOL POISONING.

PMID- 18731120
TI  - COMPARATIVE ROENTGENOGRAPHIC AND MICROSCOPIC PATTERNS IN BONE TUMORS.

PMID- 18731121
TI  - MEDICAL PROGRESS: RECENT PROGRESS IN THE TREATMENT OF THROMBOEMBOLIC DISEASE.

PMID- 18731122
TI  - The Clinical Significance of Protein.

PMID- 18731123
TI  - Penicillin Treatment of Resistant Subacute Bacterial Endocarditis.

PMID- 18731124
TI  - New Industrial Accident Fee Schedule.

PMID- 18731126
TI  - In Memoriam.

PMID- 18731125
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731127
TI  - INFORMATION-Purpose and Progress of the Hospital Survey in California.

PMID- 18731128
TI  - CANCER OR CANCERS?

PMID- 18731129
TI  - POST-ONCOLYTIC IMMUNITY.

PMID- 18731130
TI  - MEDICAL JURISPRUDENCE: MALPRACTICE; SUFFICIENCY OF EVIDENCE; CORRECTNESS OF
      DIAGNOSIS.

PMID- 18731131
TI  - THE NATURAL HISTORY OF HEMOLYTIC STREPTOCOCCUS SORE THROAT.

PMID- 18731132
TI  - TREATMENT OF DISEASES OF VIRUS ORIGIN.

PMID- 18731133
TI  - TROPICAL ACNE.

PMID- 18731134
TI  - SOME FUNDAMENTALS IN ESTROGEN THERAPY.

PMID- 18731136
TI  - INDICATIONS FOR THE USE OF ELECTROSHOCK TREATMENT OF OUT-PATIENTS.

PMID- 18731135
TI  - DIVERTICULUM OF THE ANTERIOR URETHRA: REPORT OF AN ACQUIRED TYPE.

PMID- 18731137
TI  - A CASE OF COCCIDIOSIS IN MAN.

PMID- 18731139
TI  - The A.M.A. and the Rich Report.

PMID- 18731138
TI  - MEDICAL PROGRESS-RHEUMATOID SPONDYLITIS: ITS GENERAL FEATURES AND MANAGEMENT.

PMID- 18731140
TI  - Encephalitis in California and the Pacific Area.

PMID- 18731141
TI  - WHAT? AGAIN?

PMID- 18731142
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731143
TI  - In Memoriam.

PMID- 18731144
TI  - INFORMATION: TREND TOWARD VOLUNTARY HEALTH INSURANCE.

PMID- 18731145
TI  - SURFACE PHAGOCYTOSIS.

PMID- 18731146
TI  - ISOLATION OF Rh-HAPTEN.

PMID- 18731147
TI  - MEDICAL JURISPRUDENCE: HOSPITALS: NEGLIGENT CARE OF PATIENT FOLLOWING AN
      OPERATION; FAILURE TO DISCOVER PRESENCE OR PREVENT DEVELOPMENT OF TETANUS.

PMID- 18731148
TI  - THE MOST UNPHYSIOLOGICAL PERIOD OF LIFE.

PMID- 18731149
TI  - IMMEDIATE MANAGEMENT OF AMPUTATIONS OF THE HANDS, FEET AND DIGITS.

PMID- 18731150
TI  - PRIMARY TREATMENT OF OPEN WOUNDS OF THE HAND.

PMID- 18731151
TI  - INFECTION OF THE HAND, WITH EVOLUTION OF CHEMOTHERAPY.

PMID- 18731152
TI  - AMPUTATIONS OF THE HAND AND FINGERS.

PMID- 18731153
TI  - JOINTS OF THE HAND AND FINGERS-THEIR STIFFNESS, SPLINTING AND SURGERY.

PMID- 18731154
TI  - USE OF THE BLANCHARD MECHANOTHERAPIST IN TREATING POSTOPERATIVE ATELECTASIS.

PMID- 18731155
TI  - FATAL MYOCARDITIS WITH COMPLETE HEART BLOCK FROM DIPHTHERIA.

PMID- 18731156
TI  - TYPHUS FEVER IN THE SECOND WORLD WAR.

PMID- 18731158
TI  - A Stronger Front Against State Medicine.

PMID- 18731157
TI  - MEDICAL PROGRESS: RECENT PROGRESS IN PEDIATRICS.

PMID- 18731160
TI  - Surveys for 1947.

PMID- 18731159
TI  - Antihistaminic Drugs and Nasal Vasoconstrictors.

PMID- 18731161
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731162
TI  - In Memoriam.

PMID- 18731164
TI  - "GAMMA-666" vs. DDT.

PMID- 18731166
TI  - ECZEMA "KEYSTONE OF SKIN DISEASE" SAY TWO NEW YORK DOCTORS.

PMID- 18731165
TI  - ANTICARCINOGENIC SERUM.

PMID- 18731167
TI  - MEDICAL JURISPRUDENCE: HOSPITALS: DISTRICTS; CONSTITUTIONALITY OF THE LOCAL
      HOSPITAL DISTRICT LAW.

PMID- 18731168
TI  - INFORMATION: SUGGESTED PROGRAM FOR DEVELOPMENT OF BLOOD BANK SERVICES IN
      CALIFORNIA.

PMID- 18731169
TI  - RECOVERY FROM A SURELY FATAL DOSE OF EPINEPHRINE.

PMID- 18731170
TI  - MEDICAL JURISPRUDENCE: MALPRACTICE: DEGREE OF SKILL REQUIRED OF A SURGEON: ACTS
      CONSTITUTING NEGLIGENCE IN TREATMENT.

PMID- 18731171
TI  - TREATMENT OF BACTERIAL MENINGITIS WITH PENICILLIN, SULFONAMIDES, AND SERA.

PMID- 18731172
TI  - THE TREATMENT OF PNEUMOCOCCIC PNEUMONIA WITH PENICILLIN AND SULFADIAZINE.

PMID- 18731173
TI  - ANTIBIOTICS IN THE TREATMENT OF HEMOLYTIC STREPTOCOCCUS SORE THROAT.

PMID- 18731174
TI  - NITROUS OXIDE AND OXYGEN ANESTHESIA WITH CURARE RELAXATION.

PMID- 18731175
TI  - POISON OAK-NEW ANTIGENS AND THEIR EFFECT ON SENSITIZED GUINEA PIGS.

PMID- 18731176
TI  - THIOURACIL IN THYROID DISEASES.

PMID- 18731177
TI  - IMPROVED FORMS OF INSULIN: ADVANTAGES OF MODIFIED PROTAMINE ZINC INSULIN.

PMID- 18731179
TI  - The Use of Vitamin Supplements.

PMID- 18731178
TI  - MEDICAL PROGRESS: RECENT ADVANCES IN NEUROLOGY.

PMID- 18731180
TI  - The Coming 1947 Annual Meeting.

PMID- 18731181
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731182
TI  - In Memoriam.

PMID- 18731184
TI  - Health Insurance Propaganda.

PMID- 18731183
TI  - Aerosol Therapy.

PMID- 18731186
TI  - In appreciation of Dr. Harold Philips Hill.

PMID- 18731185
TI  - CALIFORNIA MEDICAL ASSOCIATION: NEWS OF THE DAY IN THE C. M. A.

PMID- 18731189
TI  - SOVIET "ACS" THERAPY.

PMID- 18731187
TI  - In Memoriam.

PMID- 18731190
TI  - MEDICAL JURISPRUDENCE: MALPRACTICE-SUFFICIENCY OF EVIDENCE FROM WHICH A JURY MAY
      DRAW CONCLUSIONS.

PMID- 18731191
TI  - PUBLIC RELATIONS OF A STATE MEDICAL SOCIETY.

PMID- 18731192
TI  - SOME CLINICAL ASPECTS OF RHEUMATIC FEVER IN THE ADULT ON THE PACIFIC COAST.

PMID- 18731193
TI  - THE ELECTROCARDIOGRAM IN THE DIAGNOSIS AND MANAGEMENT OF RHEUMATIC FEVER.

PMID- 18731194
TI  - THE DIFFERENTIAL DIAGNOSIS OF ADULT RHEUMATIC FEVER AND RHEUMATOID ARTHRITIS.

PMID- 18731196
TI  - RHEUMATIC FEVER CONTROL PROGRAM IN CALIFORNIA.

PMID- 18731195
TI  - PUBLIC MEASURES FOR THE CONTROL OF RHEUMATIC FEVER IN ENGLAND.

PMID- 18731197
TI  - DIAGNOSIS AND TREATMENT OF ARTERIOVENOUS ANEURYSM IN A NAVAL HOSPITAL.

PMID- 18731198
TI  - FRACTIONAL SPINAL ANESTHESIA FOR SHORT UPPER ABDOMINAL SURGERY.

PMID- 18731199
TI  - POISON OAK-NEW ANTIGENS AND THEIR EFFECT ON SENSITIZED PATIENTS.

PMID- 18731200
TI  - THE NEWER DRUGS FOR ALLERGIC DISORDERS AND THEIR PLACE IN THE HISTAMIN THEORY.

PMID- 18731202
TI  - The Relation of the General Practitioner to the Practice of Medicine in
      Hospitals.

PMID- 18731201
TI  - MEDICAL PROGRESS: PROGRESS IN THE TREATMENT OF CARCINOMA OF THE PROSTATE.

PMID- 18731204
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731203
TI  - Nursing at the Crossroads.

PMID- 18731205
TI  - In Memoriam.

PMID- 18731206
TI  - Dr. George Thomason.

PMID- 18731207
TI  - INFORMATION: THE POLIOMYELITIS COORDINATING COUNCIL'S ROLE IN THE 1946 EPIDEMIC
      IN LOS ANGELES.

PMID- 18731209
TI  - REHABILITATION OF TUBERCULOUS PATIENTS.

PMID- 18731208
TI  - CANCER AND THE EMBRYONAL HYPOTHESIS.

PMID- 18731210
TI  - MEDICINE'S CHALLENGE.

PMID- 18731211
TI  - THE INCREASING IMPORTANCE OF Q FEVER INFECTION.

PMID- 18731212
TI  - THE TREATMENT OF MALIGNANT MELANOMA-REPORT OF 862 CASES.

PMID- 18731213
TI  - RUPTURE OF THE HEART.

PMID- 18731214
TI  - RESPIRATORY MOLD ALLERGY-A 12 MONTHS' ATMOSPHERIC SURVEY IN SAN FRANCISCO.

PMID- 18731215
TI  - USE OF SULFASUXIDINE IN RESECTION OF CARCINOMA OF THE COLON-EFFECT ON INFECTION
      AND MORTALITY.

PMID- 18731216
TI  - CONTROLLED EVALUATION OF GOLD THERAPY IN RHEUMATOID ARTHRITIS.

PMID- 18731217
TI  - CANCER MORTALITY IN SAN FRANCISCO.

PMID- 18731218
TI  - ACUTE HEMATOGENOUS OSTEOMYELITIS TREATED WITH PENICILLIN-A CASE REPORT.

PMID- 18731219
TI  - THE PULSE IN ANCIENT CHINESE MEDICINE.

PMID- 18731220
TI  - MEDICAL PROGRESS: PROGRESS IN THE MANAGEMENT OF SYPHILIS.

PMID- 18731221
TI  - Coronary Insufficiency.

PMID- 18731222
TI  - Public Relations and Medicine.

PMID- 18731223
TI  - Compulsory Government Health Service.

PMID- 18731224
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731225
TI  - In Memoriam.

PMID- 18731227
TI  - PREVENTION OF TISSUE ANOXIA.

PMID- 18731228
TI  - MEDICAL JURISPRUDENCE: APPLICATION OF STATUTE OF LIMITATIONS IN A MALPRACTICE
      ACTION.

PMID- 18731229
TI  - ROENTGENOLOGY IN CHRONIC MASTOIDITIS.

PMID- 18731230
TI  - SUBACUTE GENERALIZED NEUROMUSCULAR EXHAUSTION - A REPORT OF THREE CASES.

PMID- 18731231
TI  - THE PRESENT STATUS OF SURGERY IN CONGENITAL HEART DISEASE.

PMID- 18731232
TI  - AN EVALUATION OF TOPICAL PENICILLIN THERAPY; REVIEW OF RECENT LITERATURE.

PMID- 18731234
TI  - CUTANEOUS REACTION TO PENICILLIN.

PMID- 18731233
TI  - TREATMENT OF INTERSTITIAL CYSTITIS.

PMID- 18731235
TI  - ESTROGEN TREATMENT OF CHRONIC URETHRITIS IN THE FEMALE.

PMID- 18731236
TI  - THE PRESENT-DAY TREATMENT OF ASTHMA.

PMID- 18731237
TI  - FRACTURE OF THE OLECRANON PROCESS DUE TO MUSCLE PULL WITH THE FOREARM IN
      HYPEREXTENSION.

PMID- 18731238
TI  - NEUROLOGICAL COMPLICATIONS TO TREATMENT WITH RABIES VACCINE.

PMID- 18731240
TI  - Vagotomy for Peptic Ulcer.

PMID- 18731239
TI  - THE CANCER PROBLEM-CHAPTER I OF THE CALIFORNIA CANCER COMMISSION STUDIES.

PMID- 18731241
TI  - Democracy Prevails Again.

PMID- 18731242
TI  - Diagnostic Medical Care and Lay Laboratories.

PMID- 18731244
TI  - In Memoriam.

PMID- 18731243
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731245
TI  - Salute to a Gentleman.

PMID- 18731247
TI  - MEDICAL JURISPRUDENCE: NEGLIGENCE: RES IPSA LOQUITUR.

PMID- 18731248
TI  - PHYSIOLOGIC AND SURGICAL CONSIDERATIONS IN THE TREATMENT OF DUODENAL ULCERS.

PMID- 18731249
TI  - SOME NOTES ON THE Rh AND Hr FACTORS.

PMID- 18731250
TI  - EXCRETORY CYSTOGRAMS AFTER VOIDING.

PMID- 18731251
TI  - MANAGEMENT OF CARDIOSPASM.

PMID- 18731253
TI  - SOME FEATURES OF PSYCHIATRIC PRACTICE IN POSTWAR MEDICAL CARE PLANNING.

PMID- 18731252
TI  - CALIFORNIA'S PLAN FOR THE STUDY AND CONTROL OF MOSQUITO-BORNE DISEASES.

PMID- 18731254
TI  - OFFICIAL MEDICAL INVESTIGATION OF DEATHS IN BEHALF OF PUBLIC WELFARE.

PMID- 18731255
TI  - PARENTERAL FLUID THERAPY DURING PROLONGED SURGERY.

PMID- 18731257
TI  - MEDICAL PROGRESS: DICUMAROL.

PMID- 18731256
TI  - ANCIENT CHINESE SURGERY: ACUPUNCTURE.

PMID- 18731258
TI  - PRINCIPLES IN THE TREATMENT OF CANCER.

PMID- 18731259
TI  - EXAMINATION OF THE PATIENT FOR CANCER: CHAPTER III.

PMID- 18731260
TI  - Sulfonamide Therapy of Intestinal Disorders.

PMID- 18731261
TI  - CALIFORNIA MEDICAL ASSOCIATION: WOMAN'S AUXILIARY REPORTS ON YEAR'S ACTIVITIES.

PMID- 18731262
TI  - In Memoriam.

PMID- 18731264
TI  - ASCORBIC ACID WITHHOLDING THERAPY.

PMID- 18731265
TI  - THE USE AND ABUSE OF DESICCATED THYROID.

PMID- 18731266
TI  - THE RELATION OF DEEP ROENTGEN THERAPY TO AERO-OTITIS MEDIA.

PMID- 18731268
TI  - ASPHYXIAL DEATH DUE TO PULMONARY CRYPTOCOCCOSIS, A CASE REPORT.

PMID- 18731267
TI  - URACHAL CYSTS WITH MALIGNANT INVASION OF THE BLADDER-THREE CASE REPORTS.

PMID- 18731269
TI  - MEDICAL PROGRESS: TREATMENT OF THE ANEMIAS.

PMID- 18731270
TI  - CANCER COMMISSION STUDIES, Chapter IV, Biopsy-Indications, Technic and
      Safeguards.

PMID- 18731271
TI  - Current Trends in Research on Eclampsia.

PMID- 18731272
TI  - The A.M.A. Centennial.

PMID- 18731273
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731274
TI  - In Memoriam.

PMID- 18731276
TI  - VIRAL HEPATITIS AND THE PUBLIC HEALTH.

PMID- 18731277
TI  - CYCLODIALYSIS, MULTIPLE OR SINGLE, WITH AIR INJECTION-AN OPERATIVE TECHNIQUE FOR
      CHRONIC GLAUCOMA.

PMID- 18731278
TI  - THE TREATMENT OF ACUTE HEMATOGENOUS OSTEOMYELITIS WITH PENICILLIN AND
      SULFONAMIDES COMBINED.

PMID- 18731279
TI  - QUINIDINE IN HEART DISEASE, PARTICULARLY IN THE OLDER AGE GROUPS.

PMID- 18731280
TI  - THE PHARMACOLOGY OF NEW DRUGS USEFUL IN PEDIATRIC PRACTICE.

PMID- 18731281
TI  - VECTOR POTENTIALITIES WITH RESPECT TO THE SPREAD OF INSECT-BORNE DISEASES OF MAN
      IN CALIFORNIA.

PMID- 18731282
TI  - PROCTOLOGY FOR THE GENERAL PRACTITIONER.

PMID- 18731283
TI  - BLOOD PROTEIN DEPLETION IN INFANTILE ECZEMA.

PMID- 18731284
TI  - THE BLALOCK OPERATION FOR CONGENITAL PULMONARY STENOSIS.

PMID- 18731285
TI  - SIMPLIFIED INTESTINAL INTUBATION WITH MILLER-ABBOTT TUBE.

PMID- 18731286
TI  - ANESTHESIA FOR THE CHRONIC POLIOMYELITIS PATIENT.

PMID- 18731288
TI  - ACUTE ILEOCOLITIS: A CASE REPORT.

PMID- 18731287
TI  - THE USE OF ANTIBIOTICS IN SURGICAL PRACTICE.

PMID- 18731290
TI  - CANCER COMMISSION STUDIES, Chapter V, Diagnosis and Radiation Therapy of Cancer.

PMID- 18731289
TI  - MEDICAL PROGRESS: RECENT PROGRESS IN PULMONARY MYCOTIC INFECTIONS.

PMID- 18731291
TI  - The Dodo Flies Again.

PMID- 18731292
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731293
TI  - In Memoriam.

PMID- 18731295
TI  - MEDICAL JURISPRUDENCE: OPERATIONS UPON PERSONS LEGALLY INCOMPETENT TO CONSENT;
      RESTORATION TO CAPACITY TO CONSENT.

PMID- 18731296
TI  - INDICATIONS FOR SURGERY OF THE OVARY.

PMID- 18731298
TI  - Viral Diseases-A Panel Discussion.

PMID- 18731297
TI  - THE ETIOLOGY AND EPIDEMIOLOGY OF THE VIRUS GROUP OF ENCEPHALITIDES.

PMID- 18731299
TI  - CLINICAL ASPECTS OF THE ENCEPHALITIDES.

PMID- 18731300
TI  - PRESENT CONCEPTS OF THE EPIDEMIOLOGY OF POLIOMYELITIS.

PMID- 18731301
TI  - VIRAL PNEUMONIAS.

PMID- 18731302
TI  - RECENT ADVANCES IN THE DIAGNOSIS AND PREVENTION OF MUMPS AND MEASLES.

PMID- 18731303
TI  - INFLUENZA-A REVIEW OF RECENT DEVELOPMENTS.

PMID- 18731304
TI  - VIRAL STUDIES ON THE ETIOLOGY OF EPIDEMIC DIARRHEA OF THE NEWBORN.

PMID- 18731305
TI  - SYMPTOMS OF ACUTE PANCREATITIS.

PMID- 18731306
TI  - SPONTANEOUS FRACTURE OF THE FIRST RIB DUE TO MUSCLE PULL, A Case Report.

PMID- 18731307
TI  - MEDICAL PROGRESS: AMEBIASIS-PATHOLOGY, DIAGNOSIS AND RECENT DEVELOPMENTS IN
      THERAPY.

PMID- 18731308
TI  - CANCER COMMISSION STUDIES, Chapter VI, Sarcoma of Soft Tissues.

PMID- 18731309
TI  - Medical Care in Hospitals.

PMID- 18731310
TI  - An "E" for Medicine.

PMID- 18731312
TI  - In Memoriam.

PMID- 18731311
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731313
TI  - INFORMATION: CONGRESSIONAL COMMITTEE CHARGES MISUSE OF GOVERNMENT FUNDS BY
      AGENCIES PLUMPING FOR HEALTH INSURANCE.

PMID- 18731315
TI  - WHAT'S NEW IN PERIPHERAL VASCULAR DISEASE.

PMID- 18731314
TI  - WHAT'S NEW IN GASTRO-ENTEROLOGY.

PMID- 18731316
TI  - WHAT'S NEW IN TROPICAL MEDICINE.

PMID- 18731317
TI  - WHAT'S NEW IN CARDIOVASCULAR DISEASE.

PMID- 18731319
TI  - WHAT'S NEW IN ENDOCRINOLOGY.

PMID- 18731318
TI  - WHAT'S NEW IN SYPHILIS.

PMID- 18731320
TI  - WHAT'S NEW IN ALLERGY.

PMID- 18731321
TI  - RECENT ADVANCES IN PULMONARY DISEASES.

PMID- 18731322
TI  - WHAT'S NEW IN INFECTIOUS DISEASES.

PMID- 18731323
TI  - EARLY PERSONALITIES AND HYGIENE AT THE UNIVERSITY OF CALIFORNIA.

PMID- 18731324
TI  - PLASTIC SURGERY OF THE NARES.

PMID- 18731325
TI  - PERIARTERITIS NODOSA (Panarteritis Nodosa) WITH REPORT OF FOUR PROVEN CASES.

PMID- 18731327
TI  - Blood Banks in California.

PMID- 18731326
TI  - CANCER COMMISSION STUDIES, Chapter VII, Childhood Cancer.

PMID- 18731329
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731328
TI  - Mr. DeVoto Thinks-This Far.

PMID- 18731331
TI  - George Herbert Evans.

PMID- 18731330
TI  - In Memoriam.

PMID- 18731333
TI  - MEDICAL JURISPRUDENCE: MALPRACTICE; SUFFICIENCY OF EVIDENCE; QUALIFICATIONS OF
      PHYSICIAN TESTIFYING AS EXPERT WITNESS.

PMID- 18731334
TI  - INTERPRETATION OF GASTRIC SYMPTOMS.

PMID- 18731335
TI  - THE SURGICAL TREATMENT OF BLEEDING PEPTIC ULCER.

PMID- 18731336
TI  - CERTAIN ROENTGEN MANIFESTATIONS OF GASTRIC LESIONS.

PMID- 18731337
TI  - PSYCHOSOMATIC CONSIDERATIONS OF GASTRIC DISEASE.

PMID- 18731338
TI  - MEDICAL TREATMENT VERSUS PREVENTION OF PEPTIC ULCER.

PMID- 18731339
TI  - VAGUS RESECTION FOR PEPTIC ULCER.

PMID- 18731340
TI  - CONGESTIVE SPLENOMEGALY (BANTI'S SYNDROME) DUE TO PORTAL STENOSIS.

PMID- 18731341
TI  - PENTOTHAL INTERVIEW IN THE TREATMENT OF CHRONIC ALCOHOLISM.

PMID- 18731342
TI  - CANCER COMMISSION STUDIES, Chapter VIII, Malignant Lymphoma.

PMID- 18731343
TI  - Antiviral Processes.

PMID- 18731344
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731346
TI  - INFORMATION: AMCP GOES TO WORK.

PMID- 18731345
TI  - In Memoriam.

PMID- 18731348
TI  - THE PLACE OF RADIATION THERAPY IN THE MANAGEMENT OF BREAST CANCER.

PMID- 18731347
TI  - THE BLEEDING NIPPLE AS A DIAGNOSTIC AND THERAPEUTIC PROBLEM.

PMID- 18731349
TI  - MANAGEMENT OF INOPERABLE CANCER OF THE BREAST.

PMID- 18731350
TI  - RURAL MEDICAL CARE AND HOSPITALIZATION.

PMID- 18731351
TI  - ORAL SUBSTITUTION THERAPY WITH BENZESTROL FOR PATIENTS WITH ESTROGEN DEFICIENCY.

PMID- 18731352
TI  - WARTS.

PMID- 18731354
TI  - URETERAL REFLUX.

PMID- 18731353
TI  - OVERLOOKED FOREIGN BODY IN THE TRACHEOBRONCHIAL TREE: CASE REPORT.

PMID- 18731355
TI  - LEUKONYCHIA.

PMID- 18731356
TI  - DOES MILK "MAKE MUCUS"?

PMID- 18731357
TI  - A FURTHER STUDY OF PNEUMONIA IN SAN FRANCISCO, 1944-1946.

PMID- 18731358
TI  - A CAUSE FOR THE REESTABLISHMENT OF COMMUNICATION FOLLOWING LIGATION OF PATENT
      DUCTUS ARTERIOSUS.

PMID- 18731359
TI  - CALIFORNIA CANCER COMMISSION STUDIES, Chapter XI, Cancer of the Lip.

PMID- 18731360
TI  - Vascular Surgery.

PMID- 18731362
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731361
TI  - That Dodo Again.

PMID- 18731363
TI  - In Memoriam.

PMID- 18731364
TI  - PAINFUL BREAST.

PMID- 18731366
TI  - MEDICAL JURISPRUDENCE: HOSPITALS: LIABILITY-DEGREE OF CARE.

PMID- 18731367
TI  - THE DIAGNOSIS OF EARLY BREAST CANCER.

PMID- 18731369
TI  - Responsibility of the General Practitioner in Neoplastic Disease.

PMID- 18731368
TI  - Cancer of the Tonsil and Pharynx.

PMID- 18731370
TI  - Alcohol and Man.

PMID- 18731371
TI  - Not By the Back Door.

PMID- 18731372
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731373
TI  - In Memoriam.

PMID- 18731374
TI  - Clarence Gaines Toland-1875-1947.

PMID- 18731375
TI  - INFORMATION: SUGGESTED PROGRAM FOR PUBLIC RELATIONS FOR THE AMERICAN COLLEGE OF
      CHEST PHYSICIANS.

PMID- 18731376
TI  - LOW BACK PAIN FROM THE ORTHOPEDIC STANDPOINT.

PMID- 18731377
TI  - A CONSIDERATION OF ETIOLOGY IN THE DEVELOPMENT OF THE RUPTURED INTERVERTEBRAL
      DISC.

PMID- 18731378
TI  - LOW BACK PAIN AND ITS MANAGEMENT BY THE GENERAL SURGEON.

PMID- 18731379
TI  - BACK PAIN FROM THE GYNECOLOGICAL STANDPOINT.

PMID- 18731380
TI  - PYLORIC STENOSIS NOT A DISEASE OF "FIRST-BORN".

PMID- 18731381
TI  - GRANULOMA INGUINALE.

PMID- 18731383
TI  - PSYCHONEUROSIS BASED ON ORGANIC AILMENT CURED BY ELECTRIC SHOCK THERAPY.

PMID- 18731382
TI  - THE FAMILY PHYSICIAN AND MEDICAL EDUCATION.

PMID- 18731385
TI  - BENIGN AND MALIGNANT PREPYLORIC LESIONS OF THE STOMACH.

PMID- 18731384
TI  - PERINEPHRIC ABSCESS SECONDARY TO RENAL INFECTION.

PMID- 18731386
TI  - OTOLOGICAL DIAGNOSTIC CLINICS OF CALIFORNIA.

PMID- 18731387
TI  - MEDICAL PROGRESS: OPHTHALMOLOGICAL PROGRESS: SIGHT RESTORATION BY CORNEAL
      TRANSPLANT.

PMID- 18731388
TI  - PRIMARY SPINDLE CELL FIBROMYOSARCOMA OF THE GALLBLADDER.

PMID- 18731389
TI  - CHYLOTHORAX.

PMID- 18731390
TI  - CARDIAC CALCIFICATIONS, ANNULAR AND VALVULAR (LEAFLET).

PMID- 18731392
TI  - MAJOR TRIGEMINAL NEURALGIA: AN ANALYSIS OF TWO HUNDRED AND FORTY-FIVE CASES.

PMID- 18731391
TI  - ROENTGEN CARDIAC KYMOGRAPHY: ELECTROCARDIOGRAPHIC CORRELATION.

PMID- 18731393
TI  - RELATIONSHIP OF THE HEALTH OFFICER AND THE PRACTICING PHYSICIAN TO THE PLANNING
      OF SMALLER HOSPITAL AND HEALTH CENTER FACILITIES IN CALIFORNIA.

PMID- 18731394
TI  - A TULAREAN LOOKS AT TULAREMIA.

PMID- 18731395
TI  - THE TREATMENT OF EPILEPSY WITH METHYLPHENYLETHYL HYDANTOIN (MESANTOIN).

PMID- 18731396
TI  - ACUTE PUERPERAL MASTITIS-A REVIEW.

PMID- 18731397
TI  - EMOTIONAL FACTORS IN OBSTETRICAL PRACTICE.

PMID- 18731398
TI  - THE CHOREIFORM SYNDROME; ITS SIGNIFICANCE IN CHILDREN'S BEHAVIOR PROBLEMS.

PMID- 18731399
TI  - THE CLINICAL SIGNIFICANCE OF CHRONIC PARAMETRITIS.

PMID- 18731400
TI  - MEDICAL PROGRESS: ACUTE APPENDICITIS IN CHILDHOOD: A SUMMARY OF PRESENT CONCEPTS.

PMID- 18731401
TI  - PERSISTING HICCUPS, POST-ANESTHESIA RESPIRATORY DIFFICULTY.

PMID- 18731402
TI  - SCROTECTOMY FOR SCROTAL ELEPHANTIASIS.

PMID- 18731403
TI  - MESENTERIC VASCULAR OCCLUSION.

PMID- 18731404
TI  - CANCER OF THE THYROID.

PMID- 18731406
TI  - A. M. A. Interim Session.

PMID- 18731405
TI  - Non-Calculous Biliary Tract Disturbances.

PMID- 18731407
TI  - Required Reading.

PMID- 18731408
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731409
TI  - In Memoriam.

PMID- 18731410
TI  - Percy Tilson Magan.

PMID- 18731411
TI  - INFORMATION: TISSUE DIAGNOSIS DIVISION IN CALIFORNIA DEPARTMENT OF HEALTH HELD
      UNNECESSARY.

PMID- 18731412
TI  - MEDICAL JURISPRUDENCE: PHYSICIANS-MALPRACTICE-STANDARD OF CARE AND SKILL.

PMID- 18731413
TI  - RADICULAR PAIN IN THE UPPER EXTREMITY.

PMID- 18731414
TI  - DEGENERATIVE LESIONS OF THE SHOULDER AS A CAUSE OF PAIN.

PMID- 18731415
TI  - PSYCHOSOMATIC CONSIDERATIONS IN GASTROENTEROLOGY.

PMID- 18731416
TI  - BREAST CANCER IN MICE.

PMID- 18731417
TI  - WHAT ARE THE BASIC NEEDS FOR PUBLIC HEALTH IN CALIFORNIA?

PMID- 18731419
TI  - THE SECTION ON GENERAL PRACTICE-PROBLEMS, GOALS, RESPONSIBILITIES.

PMID- 18731418
TI  - PSYCHOGENIC RHEUMATISM: THE MUSCULOSKELETAL EXPRESSION OF PSYCHONEUROSIS.

PMID- 18731420
TI  - DIVERTICULOSIS AND DIVERTICULITIS OF THE COLON: A STUDY OF 100 CASES.

PMID- 18731421
TI  - SURGICAL TREATMENT OF THE HORSESHOE KIDNEY.

PMID- 18731422
TI  - THE RELATION OF THE PRIVATE PHYSICIAN TO THE CANCER CONTROL PROGRAM.

PMID- 18731423
TI  - PENICILLIN RESISTANT CASES OF SUBACUTE BACTERIAL ENDOCARDITIS SUCCESSFULLY
      TREATED WITH MASSIVE DOSAGE.

PMID- 18731425
TI  - LATENT MALARIA.

PMID- 18731424
TI  - STREPTOMYCIN TREATMENT OF TUBERCULOUS TRACHEO-BRONCHITIS.

PMID- 18731426
TI  - FRIEDREICH'S ATAXIA WITH UNUSUAL HEART COMPLICATIONS.

PMID- 18731427
TI  - CANCER OF THE LARYNX.

PMID- 18731428
TI  - CARCINOMA OF THE LUNG.

PMID- 18731429
TI  - Drastic Therapies.

PMID- 18731430
TI  - Industrial Medical Fees.

PMID- 18731431
TI  - BCG Vaccination.

PMID- 18731432
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731433
TI  - In Memoriam.

PMID- 18731435
TI  - THE RESPONSIBILITY OF MEDICINE.

PMID- 18731436
TI  - HYPERSENSITIVITY, THE COMMON DENOMINATOR OF THE COLLAGENOUS DISEASES.

PMID- 18731437
TI  - THE EARLY DIAGNOSIS AND RADICAL TREATMENT OF PROSTATIC CARCINOMA.

PMID- 18731438
TI  - THE MANAGEMENT OF ACUTE NECK INFECTIONS.

PMID- 18731439
TI  - A HEALTH DEPARTMENT'S ROLE IN THE CANCER PROGRAM.

PMID- 18731440
TI  - MYOCARDIAL INFARCTION AND HEART FAILURE.

PMID- 18731442
TI  - AN ORIGINAL TECHNIQUE FOR SURGICAL CORRECTION OF DEEP PARAVESICAL DIVERTICULA IN
      BAD RISKS.

PMID- 18731441
TI  - ARTIFICIAL INSEMINATION.

PMID- 18731443
TI  - A THERAPY OF PROVED EFFICACY IN OTOMYCOSIS.

PMID- 18731444
TI  - LEPROSY IN LOS ANGELES: A STATISTICAL STUDY OF SEVENTY-FIVE CASES.

PMID- 18731445
TI  - THE SURGICAL TREATMENT OF MIXED TUMORS OF THE PAROTID GLAND.

PMID- 18731446
TI  - A REVIEW OF COMMON OCULAR PROBLEMS IN CHILDREN.

PMID- 18731447
TI  - REINFECTION IN SYPHILIS.

PMID- 18731448
TI  - OPISTHOTONOS FETALIS IN BREECH PRESENTATION: REPORT OF A CASE WITH BILATERAL
      CONGENITAL POSTERIOR DISLOCATION OF THE TIBIAE.

PMID- 18731449
TI  - HEPATITIS WITHOUT JAUNDICE.

PMID- 18731450
TI  - HEMOTHORAX IN RELATION TO BENIGN PELVIC TUMORS.

PMID- 18731451
TI  - CARCINOMA OF THE ESOPHAGUS.

PMID- 18731452
TI  - The Laboratory and Diagnosis.

PMID- 18731453
TI  - 1948 Annual Session.

PMID- 18731454
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731455
TI  - In Memoriam.

PMID- 18731456
TI  - STANDARDS FOR SAFE USE OF CURARE.

PMID- 18731459
TI  - MEDICAL JURISPRUDENCE: CALIFORNIA STATUTES PERTAINING TO ISSUANCE OF RECIPROCITY
      LICENSE TO PRACTICE MEDICINE AND SURGERY.

PMID- 18731457
TI  - RECOVERY FROM A SUBCUTANEOUS OVERDOSE OF MORPHINE BY PROMPT INCISION AND
      DRAINAGE.

PMID- 18731460
TI  - WHAT'S NEW IN ENDOCRINOLOGY.

PMID- 18731461
TI  - WHAT'S NEW IN COMMUNICABLE DISEASES.

PMID- 18731462
TI  - RECENT DEVELOPMENTS IN TREATMENT OF PULMONARY DISEASES.

PMID- 18731463
TI  - THE SURGICAL TREATMENT OF CANCER.

PMID- 18731464
TI  - WHAT'S NEW IN GASTROENTEROLOGY.

PMID- 18731465
TI  - WHAT'S NEW IN CLINICAL PATHOLOGY.

PMID- 18731466
TI  - ANTICOAGULANT THERAPY IN POSTOPERATIVE VENOUS THROMBOSIS.

PMID- 18731467
TI  - WHAT'S NEW IN ANESTHESIA.

PMID- 18731468
TI  - WHAT'S NEW IN RADIOLOGY.

PMID- 18731469
TI  - SYPHILIS IN PREGNANCY.

PMID- 18731470
TI  - THE INCIDENCE OF UNSUSPECTED URINARY TRACT INFECTION IN A SELECTED GROUP OF
      AMBULATORY WOMEN.

PMID- 18731471
TI  - TREATMENT OF URINARY TRACT INFECTIONS.

PMID- 18731472
TI  - MEDICAL TREATMENT OF URINARY TRACT INFECTION.

PMID- 18731473
TI  - TORSION OF THE TESTICLE.

PMID- 18731474
TI  - SPLENECTOMY IN A CASE OF DISSEMINATED LUPUS ERYTHEMATOSUS WITH THROMBOCYTOPENIC
      PURPURA.

PMID- 18731476
TI  - HIATUS HERNIA: COINCIDENT HEMATEMESIS.

PMID- 18731475
TI  - VALVE DEFORMITY DURING HEALING OF SUBACUTE BACTERIAL ENDOCARDITIS.

PMID- 18731477
TI  - CANCER OF THE ORAL CAVITY.

PMID- 18731478
TI  - The "Easy Bruiser" and Medical Care Plans.

PMID- 18731479
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731480
TI  - In Memoriam.

PMID- 18731482
TI  - EXPERIMENTAL PORTACAVAL ANASTOMOSIS.

PMID- 18731483
TI  - THE PHYSICIAN'S POINT OF VIEW ON REGIONAL ORGANIZATION OF HOSPITALS.

PMID- 18731484
TI  - X-RAY DIAGNOSIS AND THERAPY IN ARTHRITIS.

PMID- 18731485
TI  - ACUTE CENTRAL (HYPOPYON) ULCERS OF THE CORNEA.

PMID- 18731486
TI  - BENADRYL AND PYRIBENZAMINE IN THE TREATMENT OF DISEASES OF THE SKIN.

PMID- 18731487
TI  - STANDARDS FOR THE DIAGNOSIS OF ACTIVITY AND INACTIVITY IN THE RHEUMATIC STATE.

PMID- 18731488
TI  - TREATMENT OF SUPERFICIAL FUNGUS INFECTIONS IN ROUTINE DERMATOLOGIC PRACTICE.

PMID- 18731490
TI  - SURGICAL OPERATIONS UPON THE AGED.

PMID- 18731489
TI  - AN EVALUATION OF INFERTILITY FACTORS.

PMID- 18731491
TI  - THE PRESENT STATUS OF FEMALE STERILIZATION TECHNIQUES IN THE UNITED STATES.

PMID- 18731492
TI  - THE DIAGNOSIS OF SCLEROMA.

PMID- 18731494
TI  - DISSECTING ANEURYSM.

PMID- 18731493
TI  - EOSINOPHILIC GRANULOMA OF BONE WITH DIFFUSE PULMONARY INVOLVEMENT.

PMID- 18731495
TI  - MEDICAL PROGRESS: ISOTOPES IN CLINICAL AND EXPERIMENTAL MEDICINE (Part I).
AB  - This is Part I of an article in two parts. Part II, Important Applications of
      Isotopes in Experimental Medicine, will appear in the August issue.

PMID- 18731496
TI  - STREPTOMYCIN THERAPY OF TUBERCULOSIS.

PMID- 18731497
TI  - CARCINOMA OF THE STOMACH.

PMID- 18731499
TI  - The C.M.A. Expands.

PMID- 18731498
TI  - CARCINOMA OF THE COLON.

PMID- 18731500
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731501
TI  - In Memoriam.

PMID- 18731502
TI  - PRACTICAL PRINCIPLES OF PSYCHOTHERAPY FOR THE NON-PSYCHIATRICALLY TRAINED
      PHYSICIAN.

PMID- 18731503
TI  - PANCREATIC LITHIASIS AND CALCIFICATION: A STUDY OF 22 CASES IN A SERIES OF 35,000
      NECROPSIES.

PMID- 18731504
TI  - A PEDIATRICIAN'S OBSERVATIONS ON MENTAL HYGIENE.

PMID- 18731505
TI  - THE TREATMENT OF CARDIOVASCULAR SYPHILIS.

PMID- 18731506
TI  - INTRAOCULAR FOREIGN BODIES IN NAVAL PERSONNEL.

PMID- 18731507
TI  - ENVIRONMENTAL SURVEY IN THE DIAGNOSIS OF ALLERGIC DISORDERS.

PMID- 18731508
TI  - FURTHER EXPERIENCES WITH PONTOCAINE-DEXTROSE EPHEDRINE FOR SPINAL ANALGESIA.

PMID- 18731510
TI  - LABORATORY PROCEDURES IN DIAGNOSIS OF BRUCELLOSIS.

PMID- 18731509
TI  - INFLAMMATION AS CONSIDERED BY THE RADIOLOGIST.

PMID- 18731511
TI  - INFLUENCE OF MERCURIAL DIURETICS ON THE EXCRETION OF SODIUM, POTASSIUM AND
      CHLORIDES.

PMID- 18731512
TI  - PARATHYROID CARCINOMA CAUSING HYPERPARATHYROIDISM.

PMID- 18731513
TI  - SEVERE STOMATITIS DUE TO ERYTHEMA MULTIFORME-ITS DIFFERENTIATION FROM HUMAN FOOT
      AND MOUTH DISEASE.

PMID- 18731514
TI  - MEDICAL PROGRESS: ISOTOPES IN CLINICAL AND EXPERIMENTAL MEDICINE.
AB  - This is Part II of an article in two parts. Part I appeared in the July issue of
      California Medicine, and with it were the list of references for the entire
      article and the Table 1 referred to in the following text.

PMID- 18731515
TI  - CANCER OF THE ANUS, RECTUM AND RECTOSIGMOID.

PMID- 18731516
TI  - What Is the C.M.A.?

PMID- 18731517
TI  - Hospitals in Practice.

PMID- 18731518
TI  - LETTERS TO THE EDITOR.

PMID- 18731519
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731520
TI  - In Memoriam.

PMID- 18731521
TI  - INFORMATION: PRACTICE OF MEDICINE BY PRIVATE NONPROFIT HOSPITALS HELD ILLEGAL.

PMID- 18731522
TI  - MEDICAL JURISPRUDENCE.

PMID- 18731523
TI  - Q FEVER IN ARTESIA, CALIFORNIA.

PMID- 18731524
TI  - Q FEVER IN CALIFORNIA.

PMID- 18731525
TI  - PRIMARY CARCINOMA OF THE LUNG: DIAGNOSIS BY CYTOLOGICAL STUDIES OF SPUTUM AND
      BRONCHIAL SECRETIONS.

PMID- 18731526
TI  - THE RESPONSE OF ARTICULAR CARTILAGE TO TRAUMA: WITH SPECIAL REFERENCE TO THE KNEE
      JOINT.

PMID- 18731527
TI  - THE ANTI-SHOCK ACTION OF SODIUM.

PMID- 18731528
TI  - THE ROLE OF THE PSYCHIATRIST IN CARDIOVASCULAR DISORDERS.

PMID- 18731529
TI  - ANESTHESIA IN THORACIC SURGICAL OPERATIONS.

PMID- 18731530
TI  - PRELIMINARY CLINICAL INVESTIGATION OF TETRAETHYLAMMONIUM CHLORIDE: WITH
      PARTICULAR REFERENCE TO DISORDERS OF THE CIRCULATORY SYSTEM.

PMID- 18731531
TI  - Q FEVER IN CENTRAL AND NORTHERN CALIFORNIA.

PMID- 18731533
TI  - BOXER'S BURSITIS.

PMID- 18731532
TI  - A FATAL CASE OF Q FEVER IN SOUTHERN CALIFORNIA.

PMID- 18731534
TI  - CHRONIC BRUCELLOSIS: A FOLLOW-UP STUDY OF 133 PATIENTS TREATED WITH OXIDIZED
      VACCINE.

PMID- 18731535
TI  - MENTAL HEALTH IN THE PUBLIC HEALTH PROGRAM.

PMID- 18731536
TI  - ILLUSTRATED ROENTGENOGRAMS-A PEDAGOGIC AID.

PMID- 18731537
TI  - PREFRONTAL LEUKOTOMY: PRELIMINARY REPORT OF 101 CASES.

PMID- 18731538
TI  - COMMUNITY HEALTH EDUCATION IN RELATION TO THE PRIVATE PHYSICIAN.

PMID- 18731540
TI  - FRIEDLANDER BACILLUS MENINGITIS.

PMID- 18731539
TI  - INTRACRANIAL METASTASES OF PRIMARY PULMONARY CARCINOMA: A DIAGNOSTIC DIFFICULTY.

PMID- 18731541
TI  - CARCINOMA OF THE LIVER, GALLBLADDER, EXTRAHEPATIC DUCTS, AND PANCREAS.

PMID- 18731542
TI  - Medicine in the Atomic Revolution.

PMID- 18731543
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731545
TI  - MEDICAL JURISPRUDENCE.

PMID- 18731546
TI  - BAL (2, 3-DIMERCAPTOPROPANOL) IN THE TREATMENT OF MASSIVE OVERDOSAGE WITH
      MAPHARSEN.

PMID- 18731547
TI  - TREATMENT OF DUODENAL ULCER BY CONSERVATIVE GASTRIC RESECTION WITH PARTIAL
      VAGOTOMY.

PMID- 18731548
TI  - ORTHOSTATIC HYPOTENSION AND ORTHOSTATIC TACHYCARDIA: NEW CLINICAL OBSERVATIONS,
      SUCCESSFUL TREATMENT WITH PAREDRINE, AND REVIEW OF LITERATURE.

PMID- 18731550
TI  - THE "PITFALL" OF NORMAL RESULTS OF URINALYSIS.

PMID- 18731549
TI  - BRONCHIAL ASTHMA IN INFANTS AND CHILDREN-ITS DIAGNOSIS AND TREATMENT.

PMID- 18731551
TI  - MASSIVE HERNIATION OF THE INTERVERTEBRAL DISC PRODUCING COMPRESSION OF THE CAUDA
      EQUINA.

PMID- 18731552
TI  - CUTANEOUS AND EPIDEMIC DIPHTHERIA.

PMID- 18731553
TI  - THE BERMAN FOREIGN-BODY LOCATOR.

PMID- 18731554
TI  - DRAINAGE WITH AN IN-DWELLING CATHETER WITHOUT INFECTION FOLLOWING A BLADDER
      INJURY.

PMID- 18731555
TI  - STREPTOMYCIN IN CRYPTOCOCCOSIS.

PMID- 18731556
TI  - PURPURA FOLLOWING TREATMENT WITH TETRAETHYLAMMONIUM CHLORIDE.

PMID- 18731557
TI  - CARCINOSARCOMA.

PMID- 18731558
TI  - MEDICAL PROGRESS: NEWER METHODS OF TREATMENT OF LEUKEMIAS AND LYMPHOMAS.

PMID- 18731559
TI  - CANCER OF THE KIDNEY AND TESTICLE.

PMID- 18731560
TI  - November 2, 1948.

PMID- 18731561
TI  - LETTERS TO THE EDITOR.

PMID- 18731563
TI  - In Memoriam.

PMID- 18731562
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731564
TI  - Philip Kingsnorth Gilman.

PMID- 18731566
TI  - WHAT'S NEW IN COMMUNICABLE DISEASES.

PMID- 18731567
TI  - WHAT'S NEW IN THE FIELD OF IMMUNIZATION.

PMID- 18731568
TI  - EXPERIMENTAL USE OF TESTOSTERONE COMPOUNDS IN PREMATURE INFANTS.

PMID- 18731569
TI  - SOME DIAGNOSTIC AND THERAPEUTIC TECHNIQUES IN CYSTIC FIBROSIS OF THE PANCREAS.

PMID- 18731570
TI  - IMPORTANT FACTORS IN THE DIAGNOSIS OF PATENT DUCTUS ARTERIOSUS.

PMID- 18731571
TI  - METATARSUS VARUS.

PMID- 18731572
TI  - WHAT'S NEW IN THE TREATMENT OF ERYTHROBLASTOSIS.

PMID- 18731573
TI  - THE PLACE OF THE NON-OPERATIVE TREATMENT IN THE THERAPY OF PERFORATED PEPTIC
      ULCER.

PMID- 18731574
TI  - MANAGEMENT OF ACUTE PERITONITIS.

PMID- 18731575
TI  - THE ROLE OF TISSUE PERMEABILITY WITH PARTICULAR REFERENCE TO THE BLOOD-BRAIN
      BARRIER IN DISEASES OF THE CENTRAL NERVOUS SYSTEM.

PMID- 18731576
TI  - THE MANAGEMENT OF ACUTE AND CHRONIC PULMONARY ABSCESS.

PMID- 18731577
TI  - ANALYSIS OF FATAL CASES OF POLIOMYELITIS.

PMID- 18731578
TI  - DANGERS OF LOCAL EXTERNAL HEAT AND TRAUMA TO ISCHEMIC TISSUES IN PERIPHERAL
      VASCULAR DISEASES.

PMID- 18731579
TI  - HEREDITARY ANGIONEUROTIC EDEMA: A REMARKABLE FAMILY HISTORY.

PMID- 18731580
TI  - CHARCOT'S JOINT WITH SECONDARY PURULENT ARTHRITIS TREATED WITH INTRA-ARTERIAL
      PENICILLIN.

PMID- 18731582
TI  - Banking on Blood.

PMID- 18731581
TI  - CANCER OF THE BREAST.

PMID- 18731584
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731583
TI  - Tuberculous Lympholysis.

PMID- 18731585
TI  - In Memoriam.

PMID- 18731587
TI  - The Heat's On.

PMID- 18731588
TI  - Woman Also Works.

PMID- 18731589
TI  - Hats Off.

PMID- 18731590
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731591
TI  - In Memoriam.

PMID- 18731593
TI  - Medicine On the March.

PMID- 18731594
TI  - In the Beginning.

PMID- 18731595
TI  - Impressions from the Rural Health Conference.

PMID- 18731597
TI  - In Memoriam.

PMID- 18731596
TI  - E. Coli Antibiotic.

PMID- 18731599
TI  - Industrial Medical Fees.

PMID- 18731600
TI  - Hospital Districts and Acorns.

PMID- 18731601
TI  - LETTERS TO THE EDITOR.

PMID- 18731602
TI  - C. P. S. Fee Schedules.

PMID- 18731603
TI  - In Memoriam.

PMID- 18731605
TI  - Ten Years After.

PMID- 18731606
TI  - The A.M.A. 12-Point Program.

PMID- 18731607
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731608
TI  - In Memoriam.

PMID- 18731609
TI  - Lambert B. Coblentz.

PMID- 18731610
TI  - MEDICAL JURISPRUDENCE: CONSENT TO THE PERFORMANCE OF OPERATIONS-INCOMPETENT
      ADULTS-RESTORATION TO COMPETENCY.

PMID- 18731611
TI  - Medical Rackets.

PMID- 18731612
TI  - Toward Better Service for Hospitalized Patients.

PMID- 18731613
TI  - Insurance-Good or Bad.

PMID- 18731614
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731615
TI  - In Memoriam.

PMID- 18731616
TI  - MEDICAL JURISPRUDENCE: COMPENSATION FOR PROFESSIONAL SERVICES RENDERED.

PMID- 18731617
TI  - Industrial Cases.

PMID- 18731618
TI  - Gluten Intoxication.

PMID- 18731619
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731620
TI  - Frederic Morris Loomis.

PMID- 18731621
TI  - John Johnson Sippy.

PMID- 18731622
TI  - In Memoriam.

PMID- 18731624
TI  - R.I.P.

PMID- 18731625
TI  - Annual Session-1949.

PMID- 18731626
TI  - Industrial Fees-What Next?

PMID- 18731627
TI  - Let's Look at the Health Map.

PMID- 18731628
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731629
TI  - In Memoriam.

PMID- 18731630
TI  - INFORMATION: LICENSURE OF FOREIGN MEDICAL GRADUATES.

PMID- 18731631
TI  - Physicians for the Armed Forces.

PMID- 18731633
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731632
TI  - Medicine and Animals.

PMID- 18731634
TI  - Local Health Officers.

PMID- 18731635
TI  - Whose Hospital Records?

PMID- 18731636
TI  - LETTERS TO THE EDITOR.

PMID- 18731637
TI  - Cytoplasmic Hereditary Determiner.

PMID- 18731638
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731639
TI  - In Memoriam.

PMID- 18731640
TI  - INFORMATION: FOUNDATION FOR HIGH BLOOD PRESSURE RESEARCH SEEKING URGENTLY NEEDED
      FUNDS.

PMID- 18731641
TI  - Doctors and Lobbies.

PMID- 18731642
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731643
TI  - In Memoriam.

PMID- 18731645
TI  - OBSTETRICIAN'S POINT OF VIEW.

PMID- 18731644
TI  - INFORMATION: MEDICAL ASPECTS OF PARATHION INSECTICIDE.

PMID- 18731647
TI  - PSYCHIATRIST'S POINT OF VIEW.

PMID- 18731646
TI  - PEDIATRICIAN'S POINT OF VIEW.

PMID- 18731649
TI  - Lobbies and Pockets.

PMID- 18731648
TI  - NURSING POINT OF VIEW.

PMID- 18731650
TI  - Life Insurance Examiner Fees.

PMID- 18731652
TI  - Immunity Potential of Diabeties.

PMID- 18731651
TI  - LETTERS TO THE EDITOR.

PMID- 18731654
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731653
TI  - Ineffective Booster Vaccines.

PMID- 18731655
TI  - In Memoriam.

PMID- 18731657
TI  - Whose Monopoly?

PMID- 18731656
TI  - INFORMATION: MUSINGS ON THE "PRESIDENT'S NEW NATIONAL HEALTH BILL".

PMID- 18731658
TI  - Neomycin.

PMID- 18731659
TI  - Undesirable Use of Magnesium Intravenously in Parathion Poisoning.

PMID- 18731660
TI  - Multiplication of Influenza Virus in Dead Chick Embryos.

PMID- 18731663
TI  - Industrial Fees Again.

PMID- 18731661
TI  - In Memoriam.

PMID- 18731664
TI  - Cancer-Inhibiting Normal Serum Component.

PMID- 18731665
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731667
TI  - A.M.A. Clinical Session.

PMID- 18731666
TI  - In Memoriam.

PMID- 18731668
TI  - The Hess Committee Report.

PMID- 18731670
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731669
TI  - Non-Paralytic Poliomyelitis.

PMID- 18731671
TI  - In Memoriam.

PMID- 18731672
TI  - The World Medical Association.

PMID- 18731674
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731673
TI  - Tuberculin "Activator".

PMID- 18731676
TI  - Catastrophe Coverage.

PMID- 18731675
TI  - In Memoriam.

PMID- 18731677
TI  - Industrial Fees for 1950.

PMID- 18731678
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731679
TI  - In Memoriam.

PMID- 18731680
TI  - LIPID METABOLISM.
AB  - In light of recent advances in the understanding of the metabolism of fats and
      other lipids, the viewpoint on the importance of fat as a dietary constituent
      should be changed. It is no longer to be considered as an optional constituent of
      the diet but as a required component. On the basis of several types of
      nutritional evaluation (growth, pregnancy, lactation) generous fat diets have
      been found to give results superior to those obtained by a low-fat regimen. Fat
      apparently plays a role in promoting protein storage in the tissues. Recent
      reports have pointed out that fairly large doses of fat have been introduced by
      vein into animals over considerable periods of time without any of the harmful
      effects noted in earlier tests. The use of isotopes, which has helped toward
      knowledge of the changes which take place in the breakdown of fat in the tissues,
      may lead to an understanding of the mechanism involved in the formation and
      destruction of the ketone acids.Cholesterol, which has been considered by many to
      be a causative agent in one type of cardiovascular disease, probably is
      manufactured in the body at a greater rate than it can originate from foods. The
      harmful effects of cholesterol may be related to the speed of synthesis and the
      rate of destruction as well as to the amount of ready-formed cholesterol taken in
      foods. One instance in which cholesterol feeds exerts a beneficial effect is in
      the case of rats suffering from overdosage of thyroid extract.

PMID- 18731681
TI  - THE NEWER ANTIBIOTICS IN DERMATOLOGY.
AB  - From the experimental and clinical observations published to date it appears that
      three new antibiotics, polymyxin, chloramphenicol and aureomycin, will prove to
      be highly efficacious against many of the infectious dermatoses and venereal
      diseases.

PMID- 18731682
TI  - WHO ARE PROSPECTIVE NEUROTICS?
AB  - Emotions of any kind and experienced at any age are etiologic factors of neuroses
      only in predisposed persons. Predisposed persons are those of neuropathic and
      psychoneuropathic constitution. This is characterized by excessive excitability
      and abnormal reactivity of the nervous system. This involves, in various degree
      and proportion, the autonomic nervous system as well as the higher cerebral
      functions including associative and emotional mental reactions. Objective signs
      of autonomic nervous imbalance can be detected by physical examination. In the
      mental sphere, psychoneurotic constitution can be recognized by emotional
      imbalance, excessive, inadequate, untimely reactions ("psychic
      dysmetry").Neuropathic and psychoneuropathic constitution per se is compatible
      with perfect health. It deserves attention, however, in that its carriers may
      play an important role in cultural and social life and so exert a great
      suggestive influence on the mass of people. The type of neurosis or
      psychoneurosis and the symptoms of it depend chiefly on the constitutional morbid
      predisposition (constitutional biologic inferiority) of certain organs or organ
      systems and on the kind of emotional situations which the patient is unable to
      cope with. The great number of neuroses, psychoneuroses and psychosomatic
      diseases among patients consulting them makes it imperative that internists and
      general practitioners be capable of making the correct diagnosis and of carrying
      out the indicated treatments by "minor psychotherapy."

PMID- 18731683
TI  - SOME PHASES OF POSTOPERATIVE ATELECTASIS-The Role of Ciliary Action in Absorption
      of Air.
AB  - The primary cause of postoperative atelectasis is the production of excessive
      quantities of mucus which occlude one or more air passages. This mucus is moved
      upward in the bronchial tree in successive masses, which carry with them bubbles
      of air, at the same time as the gases of the air are being absorbed by the venous
      blood. When all of the air has been removed, negative pressure develops which is
      equal to the effective ciliary power acting upon the contained masses of mucus.
      This negative pressure is, in all probability, maintained solely by ciliary
      action.

PMID- 18731684
TI  - THE EFFECT OF NEW DRUGS ON THE RHYTHMIC FUNCTION OF THE HEART.
AB  - Epinephrine and related drugs (sympathomimetic amines) are the only compounds
      which effectively increase the rhythmic function of the heart. Effects of two new
      non-pressor sympathomimetic compounds were observed. One of these compounds, the
      isopropyl homologue of epinephrine, was found to be about five times more active
      than epinephrine.From clinical observations on the action of a new cardiac
      depressant drug, alpha-fagarine, it was concluded that the drug is very effective
      but that toxic reactions are unpredictable. The potency of alpha-fagarine and
      related compounds suggests the possible development of chemically related non
      toxic drugs having an effective cardiac depressant action.

PMID- 18731685
TI  - SURGICAL EMERGENCIES.
AB  - Action according to preconceived plans may be life-saving at the scene of
      accidents involving serious injury to several persons. Severe hemorrhage and
      respiratory obstruction must be dealt with immediately. As the latter may not be
      apparent at a glance, it should be looked for specifically. Artificial
      respiration may be necessary. Spinal puncture is a procedure in first aid which
      should be carried out at the site of an accident if there are symptoms of
      cerebral edema or of increased cerebral pressure.Routine plans should be laid to
      meet the emergency of cardiac arrest on the operating table. The surgeon must be
      prepared to begin cardiac massage within three minutes in such instances.

PMID- 18731686
TI  - WHAT IS AN INTERNIST?

PMID- 18731687
TI  - BRONCHIAL ASTHMA IN ADULTS-Causes and Treatment.
AB  - Food and inhalant allergens were of about equal importance in producing bronchial
      asthma in 907 adults between the ages of 15 and 55 years.Drug and especially
      bacterial allergens were infrequent causes.Psychogenic factors may activate or
      exaggerate causes mentioned but were not the sole cause of any case in this
      series. Food allergens are best studied and controlled by the standardized cereal
      free elimination diet and at times other elimination diets. Test-negative diets
      usually fail because of the fallibility of both negative and positive skin tests.
      Inhalant allergy is controlled by the elimination of causative allergens by
      varying degrees of environmental control and often by pollen and dust filters in
      the window. Desensitization is necessary against those allergens that cannot be
      removed from the environment. Dilutions in the millions and billions may be
      required. Morphine and other opiates, Demerol, chloral, paraldehyde and large or
      moderate doses of barbiturates are contraindicated in bronchial asthma, as
      emphasized by deaths resulting from the use of them. Bronchoscopy is indicated
      for bronchial obstruction due to inspissated mucous plugs, but the danger of the
      procedure, especially with much sedation, must be recognized. When secondary
      infection is probable, the use of sulfadiazine, penicillin, aureomycin and
      chloramphenicol must be considered.

PMID- 18731688
TI  - TREATMENT OF MIGRAINE-Results with Dihydroergocornine Methanesulfonate (DHO-180)
      and Other Ergot Derivatives.
AB  - A comparison of nicotinic acid, a non-narcotic analgesic and a series of
      injectable and oral ergot preparations tested by various methods in treating 40
      patients with typical migraine indicate that ergot alkaloids are far superior in
      producing symptomatic relief.A comparison of ergotamine tartrate,
      dihydroergotamine (DHE-45) and dihydroergocornine (DHO-180) indicated that
      ergotamine tartrate is the most effective and perhaps the most toxic, DHE-45 is
      slightly less effective and considerably less toxic, and that DHO-180 is the
      least effective but also the least toxic. When given orally, these alkaloids were
      about half as effective as when given by injection. EC-110 (ergotamine nitrate
      with caffeine) was the most effective.DHO-180 in liquid form, given daily for one
      month, had a marked preventive effect on migraine attacks.

PMID- 18731690
TI  - A Case of Acute Porphyria: Remissions Induced with Procaine Intravenously.

PMID- 18731689
TI  - UNDESCENDED TESTES.
AB  - Orchiopexy was performed upon 152 patients. Follow-up observation was inadequate,
      but of known results 14 per cent were poor. As an increasing number of
      investigators have observed spontaneous descent of undescended testes, this
      possibility should be considered in weighing indications for operation on boys
      before the age of puberty. Coexisting clinically demonstrable hernia (59 per cent
      in this series) is an indication for early operation. Otherwise, orchiopexy may
      be best delayed, perhaps until the twelfth year. This was done in 25 per cent of
      the cases in this series. Three methods of operation were used, the Torek, the
      Cabot-Nesbit, and the Bevan. There were fewer poor results with the Torek than
      with the Cabot-Nesbit procedure. The greatest number of poor results was in cases
      in which the Bevan technique was used.

PMID- 18731691
TI  - Bile Peritonitis Due to Spontaneous Rupture of a Dilated Intrahepatic Duct:
      Report of a Case.

PMID- 18731692
TI  - Public Health Progress.

PMID- 18731693
TI  - Dietary Proteins vs. Tuberculosis.

PMID- 18731694
TI  - Know Thyself.

PMID- 18731695
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731696
TI  - In Memoriam.

PMID- 18731697
TI  - Questions and Answers about C. P. S.

PMID- 18731698
TI  - Health Insurance, the C.M.A. and the Governor.

PMID- 18731699
TI  - MEDICAL JURISPRUDENCE: UNAUTHORIZED TREATMENT-SCOPE OF CONSENT.

PMID- 18731700
TI  - The A.M.A. in San Francisco.

PMID- 18731701
TI  - Chronic Diseases and Government.

PMID- 18731702
TI  - In Memoriam.

PMID- 18731703
TI  - Questions and Answers about C. P. S.

PMID- 18731704
TI  - Professional Incomes.

PMID- 18731706
TI  - In Memoriam.

PMID- 18731705
TI  - CALIFORNIA MEDICAL ASSOCIATION: H. GORDON MACLEAN, PRESIDENT-ELECT.

PMID- 18731707
TI  - Questions and Answers about C. P. S.

PMID- 18731708
TI  - Questions and Answers about C. P. S.

PMID- 18731710
TI  - Scientists Have to Read Scientific Writing.

PMID- 18731709
TI  - 1950 Annual Session.

PMID- 18731711
TI  - C.M.A. Special Session.

PMID- 18731712
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731713
TI  - In Memoriam.

PMID- 18731715
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731714
TI  - The Hess Report and What It Means.

PMID- 18731716
TI  - In Memoriam.

PMID- 18731717
TI  - Questions and Answers about C. P. S.

PMID- 18731718
TI  - War and Doctors.

PMID- 18731719
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731720
TI  - In Memoriam.

PMID- 18731721
TI  - Questions and Answers about C. P. S.

PMID- 18731723
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731722
TI  - Hospitals - With Whose Money?

PMID- 18731725
TI  - The Doctor Draft.

PMID- 18731724
TI  - Questions and Answers about C. P. S: Billing C.P.S. Is Simple.

PMID- 18731726
TI  - In Memoriam.

PMID- 18731727
TI  - Questions and Answers about C. P. S.

PMID- 18731728
TI  - Tests for Advertisements.

PMID- 18731729
TI  - In Memoriam.

PMID- 18731730
TI  - Questions and Answers about C. P. S.

PMID- 18731731
TI  - Medical Education as It Should Be.

PMID- 18731732
TI  - Eleven Years After.

PMID- 18731734
TI  - In Memoriam.

PMID- 18731733
TI  - A Medical Corps for the Armed Services: Reprinted from the October 1950 issue of
      Surgery, Gynecology and Obstetrics.

PMID- 18731735
TI  - California Medical Association: Revised Proposed Constitution Submitted by
      Reference Committee No. 3, April 30, 1950.
AB  - Herewith is printed for the second time in California Medicine, the proposed
      C.M.A. Constitution introduced in the 1950 House of Delegates by Reference
      Committee No. 3 of that body. Included in this document is an additional proposed
      section introduced by Reference Committee No. 3 as an addendum to its original
      introduction of the proposed Constitution.Members of the Association, and
      especially members of the House of Delegates, are urged to give this proposed
      Constitution a thorough study. It contains various provisions which are different
      from existing constitutional provisions and which have been under discussion in
      the House of Delegates in the past.

PMID- 18731736
TI  - Questions and Answers about C. P. S.

PMID- 18731737
TI  - No Bargain.

PMID- 18731738
TI  - Questions and Answers about C. P. S.

PMID- 18731740
TI  - MEDICAL JURISPRUDENCE: PHYSICIANS - RES IPSA LOQUITUR - BRIEF HISTORY APPLICATION
      IN GENERAL.

PMID- 18731742
TI  - For Freedom in Medical Education.

PMID- 18731741
TI  - Treatment of Diabetes Insipidus with Propylthiouracil: Report of a Case.

PMID- 18731743
TI  - In Memoriam.

PMID- 18731744
TI  - Questions and Answers about C. P. S.

PMID- 18731745
TI  - MEDICAL JURISPRUDENCE: HOSPITALS-RES IPSA LOQUITUR.

PMID- 18731746
TI  - Medicine's Interest in the 1951 Legislature.

PMID- 18731747
TI  - The Annual Session.

PMID- 18731749
TI  - In Memoriam.

PMID- 18731748
TI  - Herbert C. Moffitt, Sr: Reprinted, by permission, from The Bulletin, San
      Francisco Medical Society, March, 1951.

PMID- 18731750
TI  - Questions and Answers about C. P. S.

PMID- 18731751
TI  - Physical Therapy.

PMID- 18731752
TI  - Prescribed Reading.

PMID- 18731753
TI  - In Memoriam.

PMID- 18731755
TI  - INFORMATION: REPORT OF JOINT COMMITTEE ON CHEST X-RAY.

PMID- 18731754
TI  - Questions and Answers about C. P. S.

PMID- 18731756
TI  - The 1951 Annual Session.

PMID- 18731757
TI  - CALIFORNIA MEDICAL ASSOCIATION: NEW CONSTITUTION, NEW BY-LAWS, NEW OFFICERS.

PMID- 18731758
TI  - In Memoriam.

PMID- 18731759
TI  - Questions and Answers about C. P. S.

PMID- 18731760
TI  - A New Study of C.P.S.

PMID- 18731761
TI  - A.M.A. 1951 Meeting.

PMID- 18731762
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731763
TI  - In Memoriam.

PMID- 18731765
TI  - Questions and Answers about C. P. S.

PMID- 18731764
TI  - Statement on Cancer Cures by the Cancer Commission of the C.M.A.
AB  - In recent months there has been a recrudescence in the daily press of claims for
      certain alleged cancer cures. Most of these receive the scant attention which
      they deserve and are soon forgotten. A few receive sensational publicity and are
      a source of considerable distress, both psychic and economic, to patients with
      cancer. In order to bring up to date the opinion of the Cancer Commission on this
      general question, it was resolved at the regular meeting of the Commission held
      in Los Angeles, May 1951, that a suitable statement bearing on this subject be
      prepared and issued to the press or to interested persons. The following is the
      statement as approved by the Commission:

PMID- 18731766
TI  - INFORMATION: YOU AND BLUE SHIELD.

PMID- 18731767
TI  - Officially Yours.

PMID- 18731768
TI  - In Memoriam.

PMID- 18731769
TI  - Questions and Answers about C. P. S.

PMID- 18731770
TI  - INFORMATION: CIVILIAN MEDICAL CARE FOR ARMY PERSONNEL.

PMID- 18731771
TI  - C.M.A. Constitution and By-Laws.

PMID- 18731772
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731773
TI  - California Medical Association: C.M.A. Constitution and By-Laws.

PMID- 18731775
TI  - Questions and Answers about C. P. S.

PMID- 18731774
TI  - In Memoriam.

PMID- 18731776
TI  - INFORMATION: NEW FORM FOR REPORTING "REPORTABLE" DISEASES.

PMID- 18731777
TI  - Medical Care on the March.

PMID- 18731778
TI  - Incidence and Importance of Thyroid Cancer.

PMID- 18731781
TI  - The A.M.A. Clinical Session.

PMID- 18731779
TI  - Questions and Answers about C. P. S.

PMID- 18731783
TI  - In Memoriam.

PMID- 18731782
TI  - CALIFORNIA MEDICAL ASSOCIATION: C.M.A. PUBLIC RELATIONS SERVICE AVAILABLE TO
      COUNTY SOCIETIES.

PMID- 18731784
TI  - Questions and Answers about C. P. S.

PMID- 18731786
TI  - LETTERS TO THE EDITOR.

PMID- 18731785
TI  - Malaria in Veterans Returning from Korea.

PMID- 18731787
TI  - Bacterial Agglutinins in Cancer.

PMID- 18731788
TI  - Endogenous Cholesterol.

PMID- 18731789
TI  - In Memoriam.

PMID- 18731790
TI  - Questions and Answers about C. P. S.

PMID- 18731791
TI  - C.M.A. and A.M.A. Meetings.

PMID- 18731792
TI  - LETTERS TO THE EDITOR.

PMID- 18731793
TI  - C.P.S. Study Committee.

PMID- 18731794
TI  - CALIFORNIA MEDICAL ASSOCIATION: PROPOSED CONSTITUTIONAL AMENDMENTS.

PMID- 18731795
TI  - In Memoriam.

PMID- 18731796
TI  - Questions and Answers about C. P. S.

PMID- 18731797
TI  - In Memoriam.

PMID- 18731799
TI  - The King County Case.

PMID- 18731798
TI  - Questions and Answers about C. P. S.

PMID- 18731800
TI  - Organ-Specific Blood Vessels.

PMID- 18731801
TI  - Public Relations at Home.

PMID- 18731802
TI  - Madera County Medical Society.

PMID- 18731804
TI  - Questions and Answers about C. P. S.

PMID- 18731803
TI  - In Memoriam.

PMID- 18731805
TI  - INFORMATION: CHANGES IN DISABILITY BENEFITS.

PMID- 18731806
TI  - The Annual Session.

PMID- 18731807
TI  - A New Problem for C.P.S.

PMID- 18731808
TI  - Cultures for Diagnosis of Diphtheria.

PMID- 18731809
TI  - Dangers of Cure-Alls: Multiple Vitamin Mixtures in Pernicious Anemia.

PMID- 18731811
TI  - Questions and Answers about C. P. S.

PMID- 18731810
TI  - In Memoriam.

PMID- 18731812
TI  - Culmination.

PMID- 18731814
TI  - In Memoriam.

PMID- 18731813
TI  - Emotional Hyperacidity.

PMID- 18731815
TI  - Questions and Answers about C. P. S.

PMID- 18731816
TI  - INFORMATION: SEVENTH NATIONAL CONFERENCE ON RURAL HEALTH.

PMID- 18731817
TI  - PHYSICIANS IN POLITICS-AS GOOD CITIZENS.

PMID- 18731818
TI  - MECHANISM OF SYNCOPE AND ACTION OF DRUGS IN COMPLETE HEART BLOCK.
AB  - The syncopal attacks of complete heart block may be due either to ventricular
      standstill or to ventricular acceleration including fibrillation. As treatment
      may be harmful unless the underlying mechanism in each case is determined, it is
      important to apply the available methods for differentiation. Epinephrine and
      certain related compounds (sympathomimetic amines) are the only effective
      substances in the therapy of ventricular arrest. Isopropyl nor-epinephrine is a
      most potent drug in the prevention and treatment of ventricular arrest and has
      the advantage that it does not dispose to fibrillation. Quinidine is unreliable
      and probably hazardous in the control of ventricular fibrillation in heart block
      as it appears to precipitate this arrhythmia.Preliminary observations indicate
      that ectopic ventricular rhythms are also induced by procaine amide in complete
      heart block.Isuprel(R) may be of value in the therapy of ventricular
      acceleration, by preventing the ventricular arrest which frequently follows the
      initial acceleration.

PMID- 18731819
TI  - AVOIDING PITFALLS IN UROLOGIC DIAGNOSIS.
AB  - EIGHT BASIC STEPS PROPERLY EXECUTED ARE NECESSARY TO CORRECT DIAGNOSIS OF URINARY
      DISORDERS: (1) History-taking, (2) general physical examination, (3) abdominal
      examination, (4) examination of external genitalia, (5) examination of the urine,
      (6) rectal examination and prostatic smear or vaginal examination, (7) tests of
      total renal function, (8) roentgenography as indicated. If these procedures are
      carried out in this order, more information will be obtained and misleading
      findings will be avoided.

PMID- 18731820
TI  - MEDICAL GROUP PRACTICE IN CALIFORNIA.
AB  - A 1950 study of group practice in California reveals 52 "true general medical
      groups" among 123 medical organizations surveyed, involving 634 full-time and 215
      part-time physicians. The groups, in contrast to the national patterns, tend to
      be larger, younger and more urban. There is also a greater tendency toward unit
      hospital affiliation (30 groups) and operation of group prepayment plans (10
      groups). In general similarity to the national scene, California groups are most
      frequently organized as private partnerships with a salary method of remuneration
      sometimes augmented by a share of net earnings. The range of medical and
      technical services offered varies widely with the size of the group. The
      combination of group prepayment, medical group practice, and coordinated medical
      hospital centers seems to offer special opportunities for satisfactory practice
      and adequate medical care.

PMID- 18731821
TI  - CONSERVATIVE AMPUTATION IN ARTERIOSCLEROSIS OBLITERANS.
AB  - Sixty-three toe and leg amputations in patients with arteriosclerosis obliterans
      were reviewed in an attempt to determine how often and under what conditions a
      toe or leg amputation gave satisfactory results, and when transmetatarsal
      amputation might better have been considered. In many cases in which toes were
      amputated, it was necessary later to amputate the leg or the thigh because of
      improper healing or spread of infection. Transmetatarsal amputations apparently
      heal frequently in carefully selected cases and permit better function in the
      foot than do toe amputations. Successful use of a prosthesis is not obtained in
      many cases after leg amputation. When this difficulty is anticipated
      transmetatarsal rather than leg amputation should be attempted, if other
      conditions warrant, since prosthesis is not necessary after transmetatarsal
      amputation.

PMID- 18731822
TI  - THE RELATIONSHIP OF THE REFERRING PHYSICIAN TO THE PSYCHIATRIST.
AB  - The relationship of the referring physician to the psychiatrist is believed to be
      of a different order than that of most physicians to one another. Certain facts
      are postulated as playing a role in this somewhat difficult relationship and
      examples from actual practice are offered as evidence. Among possible points of
      discord are mentioned: The length and cost of psychotherapy and relative youth of
      the specialty, the referring physician's hostile feelings toward it, and the
      unhelpful attitude of certain psychiatrists.

PMID- 18731823
TI  - RELATIONSHIP OF DELIVERY DATE TO PREDICTED DATE.

PMID- 18731824
TI  - RELATION OF A STREPTOCOCCUS TO EPIDEMIC POLIOMYELITIS-Studies in Etiology,
      Diagnosis and Specific Treatment.
AB  - The production in 1915 of herpes zoster or "posterior" poliomyelitis in animals
      with a streptococcus led to further research on the etiologic importance of
      streptococci in "anterior" poliomyelitis.A specific streptococcus was
      demonstrated consistently in persons with poliomyelitis and in well persons
      having contact with them or merely inhabiting an area in which poliomyelitis was
      epidemic. That the organism was not present in areas remote from contact with the
      disease was likewise demonstrated.The streptococcus has been isolated from
      filtrates of poliomyelitis virus and from the tissues and exudates which harbor
      the virus. It appears in the spinal fluid in the preparalytic stage of
      poliomyelitis and disappears from the spinal fluid during the severe stage of the
      disease. Antibody and antigen prepared from the streptococcus were used to
      determine the presence of antigen and antibody indicative of streptococcal
      infection in many patients with poliomyelitis and in well persons. The intensity
      of reaction indicating specific streptococcal antigen was directly proportional
      to the degree of paralysis in patients; the reaction was greater in persons whose
      age, sex and previous isolation from the disease would normally indicate greater
      susceptibility. The test for antibody gave opposite results. Specific agglutinins
      for the streptococcus and neutralizing antibody for the virus were present
      consistently in the serum of persons and monkeys during recovery from
      poliomyelitis. Virus produced in vitro from the associated streptococcus caused
      all the clinical and pathologic features of poliomyelitis in monkeys inoculated
      with it, and the animals that recovered from the disease thus induced were proved
      to be immune thereafter to the natural virus. Antistreptococcic serum prepared in
      horses was used to treat poliomyelitis. In a group of monkeys inoculated with the
      virus of the disease, 6 per cent of those receiving the serum before inoculation
      died of the disease; of the control group, 82 per cent. In a series of
      poliomyelitis patients treated with the serum the mortality rate was 8 per cent;
      in a control series, 21 per cent. In a series treated in all stages of the
      disease by the author, 10 per cent died; of those who did not receive the serum,
      25 per cent. An antibody has been prepared from the streptococcus which appears
      to prevent paralysis and otherwise mitigate poliomyelitis and to provide
      immunization from the disease.The conclusion is reached that the virus of
      poliomyelitis is a form of the specific streptococcus, which is the agent in
      primary infections and in the development of the immunizing antibody.

PMID- 18731825
TI  - SURGICAL DECOMPRESSION OF THE BOWEL IN PERITONITIS.
AB  - In some circumstances peritoneal infection causes distention and crowding of the
      bowel to such an extent that the effect is that of intestinal obstruction and it
      is impossible to introduce a tube far enough by physiologic routes to bring about
      deflation. The pressure upon the diaphragm then may cause pain in breathing, with
      the result that the patient does not fully expand the lungs and atelectasis
      develops in the lower lobes. In such circumstances surgical intervention to
      relieve the pressure in the bowel may be indicated. An ordinary urethral catheter
      introduced through an incision in the intestine cannot be extended far enough to
      relieve pressure in more than a few loops.A method of using a Foley catheter and
      of advancing it for greater distances inside the bowel was used in five cases
      with good results and without complications.

PMID- 18731826
TI  - Benign Lymphoreticulosis of Inoculation ("Cat-Scratch Fever").

PMID- 18731827
TI  - Tetanus Treated with Chloral Hydrate and Myanesin.

PMID- 18731828
TI  - 1952 Annual Session.

PMID- 18731829
TI  - CALIFORNIA MEDICAL ASSOCIATION: THE NEW PRESIDENT-ELECT.

PMID- 18731830
TI  - In Memoriam.

PMID- 18731831
TI  - Questions and Answers about C. P. S.

PMID- 18731832
TI  - In Memoriam.

PMID- 18731833
TI  - Q. & A. on C. P. S.

PMID- 18731834
TI  - A.M.A. Annual Meeting.

PMID- 18731836
TI  - New Lines.

PMID- 18731835
TI  - Prenatal Sex Determination.

PMID- 18731837
TI  - The Medical Services Commission.

PMID- 18731838
TI  - LETTERS TO THE EDITOR.

PMID- 18731839
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731840
TI  - In Memoriam.

PMID- 18731841
TI  - Q. & A. on C. P. S.

PMID- 18731842
TI  - PR-One Year Later.

PMID- 18731843
TI  - Psychosomatic Kidney Stones.

PMID- 18731844
TI  - In Memoriam.

PMID- 18731845
TI  - Q. & A. on C. P. S.

PMID- 18731848
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731847
TI  - LETTERS TO THE EDITOR.

PMID- 18731849
TI  - In Memoriam.

PMID- 18731850
TI  - Q. & A. on C. P. S.

PMID- 18731853
TI  - In Memoriam.

PMID- 18731852
TI  - 1953 Annual Session.

PMID- 18731854
TI  - Q. & A. on C. P. S.

PMID- 18731855
TI  - The Dean Steps Down.

PMID- 18731856
TI  - LETTERS TO THE EDITOR.

PMID- 18731857
TI  - In Memoriam.

PMID- 18731858
TI  - California Medicine Takes A New Look.

PMID- 18731859
TI  - "A Defense Against Socialized Medicine"?

PMID- 18731860
TI  - New Approach.

PMID- 18731862
TI  - Handsome Is..

PMID- 18731861
TI  - In Memoriam.

PMID- 18731863
TI  - CALIFORNIA MEDICAL ASSOCIATION: THE "PERMANENTE" PLAN: ITS ORGANIZATIONAL FORM.

PMID- 18731864
TI  - In Memoriam.

PMID- 18731865
TI  - Veterans and Politics.

PMID- 18731867
TI  - In Memoriam.

PMID- 18731866
TI  - Carcinogenic Cigarettes.

PMID- 18731868
TI  - Rectal Curarization.

PMID- 18731869
TI  - In Memoriam.

PMID- 18731870
TI  - The Practice of Medicine.

PMID- 18731871
TI  - In Memoriam.

PMID- 18731872
TI  - Honor Bright.

PMID- 18731873
TI  - VA Medical Care.

PMID- 18731874
TI  - Removal of Moles.

PMID- 18731875
TI  - Prelude.

PMID- 18731876
TI  - The World's Greatest.

PMID- 18731877
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731878
TI  - In Memoriam.

PMID- 18731879
TI  - Study of Relations Between Osteopathy and Medicine: Report to the House of
      Delegates of the American Medical Association of a Committee for the Study of
      Relations Between Osteopathy and Medicine, June 1953.

PMID- 18731880
TI  - Trouble in Paradise?

PMID- 18731881
TI  - Hand Talking Chart.

PMID- 18731882
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731883
TI  - In Memoriam.

PMID- 18731884
TI  - Tactful Collection of Overdue Accounts.

PMID- 18731885
TI  - In Memoriam.

PMID- 18731886
TI  - Training or Work?

PMID- 18731887
TI  - Poliomyelitis Viremia.

PMID- 18731888
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731889
TI  - In Memoriam.

PMID- 18731890
TI  - The Interim Session.

PMID- 18731892
TI  - New Atmosphere.

PMID- 18731891
TI  - An Unknown Bactericidal Serum Factor.

PMID- 18731893
TI  - In Memoriam.

PMID- 18731894
TI  - INFORMATION: NEW VACCINATION CERTIFICATES ISSUED FOR INTERNATIONAL TRAVEL.

PMID- 18731895
TI  - Interim Sessions.

PMID- 18731896
TI  - CALIFORNIA MEDICAL ASSOCIATION: Your C.M.A. Dues-What They Buy.

PMID- 18731897
TI  - Audio-Digest Foundation.

PMID- 18731899
TI  - CALIFORNIA MEDICAL ASSOCIATION: AUDIO-DIGEST FOUNDATION.

PMID- 18731898
TI  - Another A.M.A. Delegate.

PMID- 18731900
TI  - In Memoriam.

PMID- 18731901
TI  - Health and Welfare Plans.

PMID- 18731903
TI  - In Memoriam.

PMID- 18731902
TI  - George Henry Kress.

PMID- 18731904
TI  - Labor and Medicine.

PMID- 18731905
TI  - Can Panels Survive?

PMID- 18731906
TI  - New Health Director.

PMID- 18731907
TI  - In Memoriam.

PMID- 18731908
TI  - Doctors, Veterans and Citizens.

PMID- 18731909
TI  - In Memoriam.

PMID- 18731910
TI  - Greater Public Service.

PMID- 18731911
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731912
TI  - Medical Schools Aided.

PMID- 18731914
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731913
TI  - Ladies Present.

PMID- 18731915
TI  - In Memoriam.

PMID- 18731916
TI  - WOMAN'S AUXILIARY.

PMID- 18731918
TI  - In Memoriam.

PMID- 18731917
TI  - INFORMATION: FEDERAL MEDICINE ITS IMPACT ON THE MEDICAL CARE OF THE AMERICAN
      PEOPLE.

PMID- 18731919
TI  - WOMAN'S AUXILIARY.

PMID- 18731921
TI  - CALIFORNIA MEDICAL ASSOCIATION: CANCER OF THE FEMALE GENITAL TRACT
      RECOMMENDATIONS OF THE CANCER COMMISSION OF THE CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731920
TI  - New Industrial Fees.

PMID- 18731923
TI  - In Memoriam.

PMID- 18731922
TI  - Multiphasic Surveys: "Streamlined Diagnosis" for the Public.

PMID- 18731924
TI  - WOMAN'S AUXILIARY.

PMID- 18731925
TI  - Familial Periodic Paralysis.

PMID- 18731926
TI  - Closed Panel Medicine and the Law.

PMID- 18731928
TI  - In Memoriam.

PMID- 18731927
TI  - LETTERS TO THE EDITOR.

PMID- 18731930
TI  - Antibiotics, Skill and Judgment.

PMID- 18731929
TI  - WOMAN'S AUXILIARY.

PMID- 18731931
TI  - Problems of Research on Smog.

PMID- 18731932
TI  - LETTERS TO THE EDITOR.

PMID- 18731933
TI  - LETTERS TO THE EDITOR.

PMID- 18731934
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731935
TI  - In Memoriam.

PMID- 18731936
TI  - WOMAN'S AUXILIARY.

PMID- 18731937
TI  - Physicians and Schools.

PMID- 18731938
TI  - LETTER TO THE EDITOR.

PMID- 18731940
TI  - In Memoriam.

PMID- 18731939
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731941
TI  - James Frank Doughty, M.D.

PMID- 18731943
TI  - Allergy Skin Testing.

PMID- 18731942
TI  - WOMAN'S AUXILIARY.

PMID- 18731945
TI  - In Memoriam.

PMID- 18731944
TI  - LETTERS.

PMID- 18731947
TI  - INFORMATION: MALPRACTICE CLAIMS PREVENTION PROGRAMS ARE THEY WORTH WHILE?

PMID- 18731946
TI  - WOMAN'S AUXILIARY.

PMID- 18731948
TI  - The Physician and Community Service.

PMID- 18731950
TI  - LETTERS.

PMID- 18731949
TI  - LETTERS.

PMID- 18731952
TI  - In Memoriam.

PMID- 18731951
TI  - LETTERS.

PMID- 18731954
TI  - INFORMATION: HEALTH INSURANCE AND MEDICAL PRACTICE IN GERMANY.

PMID- 18731953
TI  - WOMAN'S AUXILIARY.

PMID- 18731955
TI  - Eisenhower and Health.

PMID- 18731957
TI  - WOMAN'S AUXILIARY.

PMID- 18731956
TI  - In Memoriam.

PMID- 18731960
TI  - WHAT'S YOUR Diagnosis?: CLINICAL-PATHOLOGICAL CONFERENCES.

PMID- 18731959
TI  - PROTECTION FOR THE POINTS OF HYPODERMIC NEEDLES.

PMID- 18731961
TI  - Poliomyelitis Immunization.

PMID- 18731962
TI  - In Memoriam.

PMID- 18731963
TI  - WOMAN'S AUXILIARY.

PMID- 18731966
TI  - In Memoriam.

PMID- 18731965
TI  - Proposed Changes in Federal Medical Services.

PMID- 18731969
TI  - Annual Session Highlights.

PMID- 18731967
TI  - WOMAN'S AUXILIARY.

PMID- 18731970
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731971
TI  - In Memoriam.

PMID- 18731972
TI  - WOMAN'S AUXILIARY.

PMID- 18731973
TI  - The A.M.A. Meeting.

PMID- 18731974
TI  - Sunday Medical Meetings.

PMID- 18731976
TI  - WOMAN'S AUXILIARY.

PMID- 18731975
TI  - In Memoriam.

PMID- 18731977
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731978
TI  - In Memoriam.

PMID- 18731979
TI  - WOMAN'S AUXILIARY.

PMID- 18731981
TI  - Back-Door Socialization.

PMID- 18731983
TI  - Poliomyelitis Vaccination.

PMID- 18731982
TI  - Chronic Prostatitis.

PMID- 18731984
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18731985
TI  - In Memoriam.

PMID- 18731986
TI  - WOMAN'S AUXILIARY: YOUR AUXILIARY'S ROLE IN AMERICAN MEDICAL EDUCATION
      FOUNDATION.

PMID- 18731987
TI  - Civil Defense-Your Responsibility.

PMID- 18731988
TI  - In Memoriam.

PMID- 18731990
TI  - Professional Liability.

PMID- 18731989
TI  - WOMAN'S AUXILIARY: THE PART PLAYED BY YOUR AUXILIARY IN CIVIL DEFENSE.

PMID- 18731991
TI  - In Memoriam.

PMID- 18731992
TI  - WOMAN'S AUXILIARY: LEGISLATION... ROLE OF THE PHYSICIAN'S WIFE.

PMID- 18731993
TI  - INFORMATION: MATERNITY PRACTICES IN HOSPITALS IN CALIFORNIA.

PMID- 18731994
TI  - Creeping, Creeping.

PMID- 18731995
TI  - CALIFORNIA MEDICAL ASSOCIATION: THE DEVELOPMENT OF THE BOARD.

PMID- 18731996
TI  - In Memoriam.

PMID- 18731997
TI  - WOMAN'S AUXILIARY: CHRISTMAS IN OUR COMMUNITIES.

PMID- 18731999
TI  - The Second Hundred.

PMID- 18731998
TI  - INFORMATION: LOS ANGELES MIDWINTER MEDICAL CONVENTION.

PMID- 18732000
TI  - LETTERS.

PMID- 18732001
TI  - Blue and Golden Opportunity.

PMID- 18732003
TI  - WOMAN'S AUXILIARY: PHYSICIANS' BENEVOLENCE... A TOP-RANKING AUXILIARY PROJECT.

PMID- 18732002
TI  - In Memoriam.

PMID- 18732004
TI  - INFORMATION: U. C. MEDICAL SCHOOL APPOINTMENTS.

PMID- 18732006
TI  - In Memoriam.

PMID- 18732005
TI  - Cancer Detection: The Present Status.

PMID- 18732007
TI  - WOMAN'S AUXILIARY: PROGRESS IN OUR MENTAL HEALTH PROGRAM.

PMID- 18732008
TI  - A Guide for Fees.

PMID- 18732010
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732009
TI  - Salk Vaccine, 1956.

PMID- 18732011
TI  - In Memoriam.

PMID- 18732012
TI  - WOMAN'S AUXILIARY: OUR WORK IN THE BLOOD BANKS.

PMID- 18732013
TI  - COBALT-60 TELETHERAPY OF INTRA-ORAL CANCER.
AB  - Forty patients with intra-oral cancer were given cobalt-60 teletherapy upon the
      primary lesion. Among the physical advantages of this method are the more precise
      direction of the beam, reduced scatter and lessened skin and bone effects. The
      period of observation of patients treated has not been long enough to warrant
      discussion of cure or permanent arrest, but the consistency and regularity of
      disappearance of the primary lesion was significant. The authors believe that for
      intra-oral cancer, cobalt-60 teletherapy should be used before radical surgical
      procedures are proposed.

PMID- 18732014
TI  - Idiopathic Acquired Hemolytic Anemia.

PMID- 18732016
TI  - The Use of Physical Therapists and Allied Personnel in Medical Practice.

PMID- 18732015
TI  - The National Library of Medicine.

PMID- 18732018
TI  - In Memoriam.

PMID- 18732017
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732019
TI  - WOMAN'S AUXILIARY.

PMID- 18732021
TI  - Physicians and Schools.

PMID- 18732022
TI  - Salk Vaccine: 1956 Emergency Dosage Schedule.

PMID- 18732023
TI  - Conferences on Physicians and Schools.

PMID- 18732024
TI  - CALIFORNIA MEDICAL ASSOCIATION: PHYSICIANS' PLACEMENT SERVICE.

PMID- 18732025
TI  - In Memoriam.

PMID- 18732026
TI  - WOMAN'S AUXILIARY.

PMID- 18732027
TI  - MENINGOENCEPHALITIS AND PNEUMONITIS DUE TO WESTERN EQUINE VIRUS.
AB  - In a series of 20 cases here presented in a study of Western equine encephalitis,
      only ten were conclusively proven by serological or histopathological methods,
      while the other ten were presumptively cases of that disease. Involvement of the
      spinal cord was of relatively low incidence. In only one case of four in which
      autopsy was done could the Western equine virus be demonstrated in the cerebral
      tissues. There was a rather high incidence of involvement of the respiratory
      tree. A high proportion of patients had complaints referable to the respiratory
      tract. Physical signs denoting disease of both the upper and lower respiratory
      tract, x-ray evidence showing bronchial and pulmonary involvement, and autopsy
      evidence of bronchopneumonia were noted frequently. All patients had fever as
      well as symptoms and physical signs of central nervous system disease.
      Differential diagnosis posed many interesting and challenging problems. The
      clinical features were those of meningoencephalitis and never a "flu-like"
      syndrome, although in several of the cases diagnosis could not be made with
      certainty for several days, until meningeal signs developed, and usually the
      patients were treated with one or several antibiotics during that time. In all
      cases in which a neutralization test for the Western equine virus was done, the
      result was either positive or inconclusive. Results of complement fixation tests
      were significant in only six cases. In seven of 13 cases in which x-ray films of
      the chest were made, streaks of increased density were noted.

PMID- 18732029
TI  - Every Last Sunday Until 2011.

PMID- 18732028
TI  - C.M.A. Centennial Session.

PMID- 18732031
TI  - Letters to the Editor.

PMID- 18732030
TI  - Sidney J. Shipman-A Tribute.

PMID- 18732033
TI  - In Memoriam.

PMID- 18732032
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732034
TI  - WOMAN'S AUXILIARY: A SUMMING UP.

PMID- 18732035
TI  - Hospital Accreditation.

PMID- 18732036
TI  - LETTERS.

PMID- 18732037
TI  - In Memoriam.

PMID- 18732038
TI  - WOMAN'S AUXILIARY.

PMID- 18732039
TI  - INFORMATION: "DISABILITY FREEZE" PROVISION OF SOCIAL SECURITY LAW.

PMID- 18732040
TI  - Radiation Exposure and Common Sense.

PMID- 18732041
TI  - Advertising Standards.

PMID- 18732042
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732044
TI  - WOMAN'S AUXILIARY: DEAR DOCTOR.

PMID- 18732043
TI  - In Memoriam.

PMID- 18732045
TI  - INFORMATION: "MEDICAL ABUSES" OF THE VA OUTPATIENT PROGRAM.

PMID- 18732046
TI  - Voluntary Health Insurance.

PMID- 18732047
TI  - WOMAN'S AUXILIARY: YOUR AUXILIARY AND LEGISLATION.

PMID- 18732048
TI  - Medicare.

PMID- 18732049
TI  - Francis T. Hodges, M. D.

PMID- 18732051
TI  - More Medicare.

PMID- 18732050
TI  - In Memoriam.

PMID- 18732052
TI  - LETTERS.

PMID- 18732053
TI  - In Memoriam.

PMID- 18732056
TI  - Legislative Time Again.

PMID- 18732057
TI  - Poliomyelitis Vaccinations.

PMID- 18732054
TI  - WOMAN'S AUXILIARY: THE YEAR AHEAD.

PMID- 18732059
TI  - In Memoriam.

PMID- 18732058
TI  - CALIFORNIA MEDICAL ASSOCIATION: TRANSFER OF PATIENTS FOR THERAPY.
AB  - The following statement regarding requests for transfer of patients from one
      county to another for certain types of therapy not available locally, was
      prepared by the Cancer Commission of the California Medical Association.

PMID- 18732060
TI  - INFORMATION: MEDICAL CARE FOR MILITARY DEPENDENTS.

PMID- 18732061
TI  - Cancer Quackery.

PMID- 18732062
TI  - Fixed Antibiotic Combinations.

PMID- 18732063
TI  - Letters to the Editor.

PMID- 18732064
TI  - In Memoriam.

PMID- 18732066
TI  - Malpractice Insurance Rates.

PMID- 18732065
TI  - WOMAN'S AUXILIARY.

PMID- 18732067
TI  - Contribution to World Peace.

PMID- 18732068
TI  - In Memoriam.

PMID- 18732071
TI  - Public Health League Honored.

PMID- 18732069
TI  - WOMAN'S AUXILIARY: A PUBLIC RELATIONS LETTER TO ALL CALIFORNIA PHYSICIANS.

PMID- 18732072
TI  - The Legislature Speaks.

PMID- 18732074
TI  - In Memoriam.

PMID- 18732073
TI  - LETTERS.

PMID- 18732075
TI  - WOMAN'S AUXILIARY: NURSE RECRUITMENT IN CALIFORNIA.

PMID- 18732077
TI  - Infectious Mononucleosis Complicated by Landry's Paralysis, Requiring Respirator
      Care.

PMID- 18732078
TI  - Physicians vs. Poliomyelitis.

PMID- 18732079
TI  - Legislative Time Again.

PMID- 18732080
TI  - LETTERS.

PMID- 18732082
TI  - In Memoriam.

PMID- 18732081
TI  - Congenital Absence of the Gallbladder.

PMID- 18732083
TI  - WOMAN'S AUXILIARY.

PMID- 18732084
TI  - INFORMATION: A Way to Gauge Hospital Needs.

PMID- 18732085
TI  - Men, Machines and Medicine.

PMID- 18732087
TI  - One Year Older.

PMID- 18732086
TI  - In Memoriam.

PMID- 18732089
TI  - In Memoriam.

PMID- 18732088
TI  - CALIFORNIA MEDICAL ASSOCIATION: FRANCIS E. WEST, M.D.

PMID- 18732090
TI  - Transactions of the House of Delegates.

PMID- 18732092
TI  - Principles of Medical Ethics.

PMID- 18732091
TI  - WOMAN'S AUXILIARY.

PMID- 18732093
TI  - Twelve Short Years.

PMID- 18732094
TI  - In Memoriam.

PMID- 18732097
TI  - Welfare and Medicine.

PMID- 18732095
TI  - WOMAN'S AUXILIARY: THE VALUE OF THE WOMAN'S AUXILIARY TO THE MEDICAL PROFESSION.

PMID- 18732098
TI  - In Memoriam.

PMID- 18732099
TI  - WOMAN'S AUXILIARY: THESE ARE YOUR WIVES.

PMID- 18732100
TI  - You and Your Mail.

PMID- 18732101
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732102
TI  - In Memoriam: Hollis Layton Carey.

PMID- 18732104
TI  - WOMAN'S AUXILIARY: THE YEAR AHEAD.

PMID- 18732103
TI  - In Memoriam.

PMID- 18732105
TI  - Industrial Medical Fees.

PMID- 18732106
TI  - LETTERS.

PMID- 18732107
TI  - In Memoriam.

PMID- 18732108
TI  - WOMAN'S AUXILIARY: PUBLIC RELATIONS.

PMID- 18732109
TI  - Joint Blood Council.

PMID- 18732110
TI  - CALIFORNIA MEDICAL ASSOCIATION: PROPOSED CONSTITUTIONAL AMENDMENT.

PMID- 18732111
TI  - In Memoriam.

PMID- 18732113
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732112
TI  - WOMAN'S AUXILIARY: NURSE RECRUITMENT.

PMID- 18732114
TI  - In Memoriam.

PMID- 18732115
TI  - WOMAN'S AUXILIARY: MEMBERSHIP.

PMID- 18732116
TI  - INFORMATION: The New Director of Mental Hygiene.

PMID- 18732117
TI  - Fluoridation of Drinking Water.

PMID- 18732118
TI  - Diagnosis of Hemorrhagic Diseases.

PMID- 18732119
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732120
TI  - In Memoriam.

PMID- 18732121
TI  - WOMAN'S AUXILIARY: REMINISCING.

PMID- 18732122
TI  - Physicians and Lawyers.

PMID- 18732124
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732123
TI  - Why a Tumor Registry?

PMID- 18732125
TI  - In Memoriam.

PMID- 18732126
TI  - WOMAN'S AUXILIARY: VOLUNTEER SERVICES THE "GEMS" PROGRAM.

PMID- 18732127
TI  - In Memoriam.

PMID- 18732129
TI  - United Funds and Voluntary Health Agencies.

PMID- 18732128
TI  - WOMAN'S AUXILIARY: PRESIDENT'S MESSAGE.

PMID- 18732130
TI  - 1958 Annual Session.

PMID- 18732131
TI  - LETTERS.

PMID- 18732133
TI  - WOMAN'S AUXILIARY: THE WORD FROM DR. ALLMAN.

PMID- 18732132
TI  - In Memoriam.

PMID- 18732134
TI  - Man vs. Automobile.

PMID- 18732135
TI  - Research by Practicing Physicians.

PMID- 18732136
TI  - In Memoriam.

PMID- 18732137
TI  - WOMAN'S AUXILIARY: REPORT OF THE PRESIDENT.

PMID- 18732138
TI  - INFORMATION: Campaign for Poliomyelitis Inoculation.

PMID- 18732139
TI  - Acute Renal Tubular Failure-A Report of Two Cases with an Unusual Mechanism of
      Poisoning Due to Sodium Chlorate.

PMID- 18732140
TI  - Welcome, A.M.A.

PMID- 18732141
TI  - C.M.A. Annual Session, 1958.

PMID- 18732142
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732143
TI  - In Memoriam.

PMID- 18732144
TI  - WOMAN'S AUXILIARY.

PMID- 18732146
TI  - The Job and the Man.

PMID- 18732145
TI  - C.M.A. Changes Structure.

PMID- 18732148
TI  - In Memoriam.

PMID- 18732147
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732149
TI  - WOMAN'S AUXILIARY.

PMID- 18732150
TI  - Milk-Alkali Syndrome, with Jaundice and Tetany.

PMID- 18732151
TI  - Gastric Diverticulum with Perforation and Generalized Peritonitis.

PMID- 18732153
TI  - A.M.A. Meeting.

PMID- 18732152
TI  - Bleeding Esophageal Varices Due to Occult Cirrhosis of the Liver.

PMID- 18732155
TI  - In Memoriam.

PMID- 18732154
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732156
TI  - PUBLIC HEALTH REPORT: Increase in Arthropod-Borne Encephalitis a Possibility.
AB  - THE COMMUNICATION below is the first of what is intended as a continuing series
      of reports from the State of California Department of Public Health on topics of
      interest to physicians in private practice. On a number of occasions in the past,
      Dr. Malcolm H. Merrill, Director of Public Health, has appeared before the
      Council of the California Medical Association with intensely interesting reports
      on matters of public health and the attitudes and functions of the department.
      Since the minutes of the meetings of the Council give only the briefest of notes
      on such communications, Dr. Merrill was asked-and has agreed-to make use of this
      section of California Medicine for public health reports that can be informative
      and useful to all members.

PMID- 18732157
TI  - WOMAN'S AUXILIARY.

PMID- 18732158
TI  - MEDICAL JURISPRUDENCE: PRACTICE OF MEDICINE; DELEGATION OF DUTIES.

PMID- 18732159
TI  - The Inimical Changes in "Medicare".

PMID- 18732160
TI  - Relative Values-A Restudy.

PMID- 18732161
TI  - Letters to the Editor.

PMID- 18732162
TI  - Letters to the Editor.

PMID- 18732164
TI  - PUBLIC HEALTH REPORT.

PMID- 18732163
TI  - In Memoriam.

PMID- 18732165
TI  - WOMAN'S AUXILIARY: COOPERATE AND ACHIEVE.

PMID- 18732166
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732167
TI  - In Memoriam.

PMID- 18732168
TI  - PUBLIC HEALTH REPORT.

PMID- 18732169
TI  - WOMAN'S AUXILIARY: MEET YOUR AUXILIARY OFFICERS 1958-1959.

PMID- 18732170
TI  - Public Assistance Medical Care.

PMID- 18732171
TI  - CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732172
TI  - In Memoriam.

PMID- 18732173
TI  - PUBLIC HEALTH REPORT.

PMID- 18732174
TI  - WOMAN'S AUXILIARY: MEET YOUR AUXILIARY OFFICERS 1958-1959.

PMID- 18732175
TI  - Physicians and Politics.

PMID- 18732176
TI  - In Memoriam.

PMID- 18732177
TI  - WOMAN'S AUXILIARY: MEET YOUR AUXILIARY OFFICERS 1958-1959.

PMID- 18732180
TI  - CALIFORNIA MEDICAL ASSOCIATION: C.M.A. EXECUTIVE DIRECTOR.

PMID- 18732179
TI  - A Survey of California Medicine.

PMID- 18732181
TI  - In Memoriam.

PMID- 18732182
TI  - PUBLIC HEALTH REPORT.

PMID- 18732183
TI  - C.M.A. ANNUAL REPORTS.

PMID- 18732184
TI  - Medical Care for the Aged.

PMID- 18732185
TI  - Heart Disease in Transport Workers.

PMID- 18732186
TI  - In Memoriam.

PMID- 18732188
TI  - WOMAN'S AUXILIARY.

PMID- 18732187
TI  - PUBLIC HEALTH REPORT.

PMID- 18732190
TI  - CALIFORNIA MEDICAL ASSOCIATION: PAUL D. FOSTER, M.D., NEW C.M.A. PRESIDENT-ELECT.

PMID- 18732189
TI  - Twenty Years After.

PMID- 18732191
TI  - In Memoriam.

PMID- 18732192
TI  - PUBLIC HEALTH REPORT.

PMID- 18732193
TI  - WOMAN'S AUXILIARY.

PMID- 18732195
TI  - New C.M.A. Secretary.

PMID- 18732194
TI  - Mr. Forand's Needle.

PMID- 18732196
TI  - CALIFORNIA MEDICAL ASSOCIATION: ARE WE MAKING THE SAME MISTAKES BRITISH DOCTORS
      MADE?
AB  - Almost every doctor who visits England comes back wanting to write an article or
      give a speech about socialized medicine. Because there has been so much said so
      many times on the subject, it has lost much of its interest.Yet, the headquarters
      of the California Academy of General Practice in San Francisco recently had a
      visitor from England who had some startling, frightening things to say of
      interest to every American doctor. The visitor was Dr. Alastair J. Marshall,
      Luton, England, who is visiting in this country under a Ford Foundation Grant. As
      an area executive in the British Medical Association and on the executive area
      council (one-third physicians, two-thirds laymen) for the national health system,
      Dr. Marshall can competently speak on this subject. Here are some of the
      questions presented to Dr. Marshall by the Academy's Executive Secretary Bill
      Rogers.

PMID- 18732197
TI  - In Memoriam.

PMID- 18732198
TI  - PUBLIC HEALTH REPORT.

PMID- 18732200
TI  - Tetanus Immunization.

PMID- 18732199
TI  - WOMAN'S AUXILIARY.

PMID- 18732201
TI  - The Future of California Physicians' Service.

PMID- 18732203
TI  - Proposed Constitutional Amendment.

PMID- 18732202
TI  - Transactions of the House of Delegates, San Francisco, February 22-25, 1959.

PMID- 18732204
TI  - In Memoriam.

PMID- 18732205
TI  - PUBLIC HEALTH REPORT.

PMID- 18732207
TI  - What Is the California Medical Assistants' Association?

PMID- 18732206
TI  - WOMAN'S AUXILIARY.

PMID- 18732208
TI  - New Mental Hygiene Director.

PMID- 18732209
TI  - Medical Examinations-When Required by Law.

PMID- 18732210
TI  - MD-Plan 65.

PMID- 18732211
TI  - Cancer Control.

PMID- 18732212
TI  - C.P.S. Medical Care Plan for "Over 65".

PMID- 18732214
TI  - PUBLIC HEALTH REPORT.

PMID- 18732213
TI  - In Memoriam.

PMID- 18732216
TI  - The A.M.A. Meeting.

PMID- 18732215
TI  - WOMAN'S AUXILIARY.

PMID- 18732217
TI  - A Win at Short Odds.

PMID- 18732218
TI  - A.M.A. President-Elect.

PMID- 18732219
TI  - Actions of the A.M.A. House of Delegates.
AB  - This skimming and skipping report on the proceedings of the House of Delegates of
      the American Medical Association at the Atlantic City meeting covers only a few
      of the many important subjects dealt with by the House and is not intended as a
      detailed report on all actions taken.

PMID- 18732220
TI  - In Memoriam.

PMID- 18732221
TI  - PUBLIC HEALTH REPORT.

PMID- 18732223
TI  - In Memoriam.

PMID- 18732222
TI  - WOMAN'S AUXILIARY.

PMID- 18732224
TI  - PUBLIC HEALTH REPORT.

PMID- 18732226
TI  - Two School Health Conferences Set.

PMID- 18732225
TI  - WOMAN'S AUXILIARY: NOW, A NEW TASK FOR THE AUXILIARY.

PMID- 18732227
TI  - GP Resolution on Hospital Privileges.

PMID- 18732228
TI  - Opposition to the Forand Bill.

PMID- 18732230
TI  - C.M.A. President Testifies in Forand Bill Hearings.
AB  - Following is the testimony of T. Eric Reynolds, M.D., President of the California
      Medical Association, before the Ways and Means Committee of the U. S. House of
      Representatives concerning H.R. 4700 (the Forand bill) July 14, 1959:

PMID- 18732229
TI  - The Physician and The Press.

PMID- 18732231
TI  - Seminars on Medico-Economic Problems.

PMID- 18732233
TI  - Labels on Medicine Bottles.

PMID- 18732232
TI  - Dealing with Third Parties.

PMID- 18732234
TI  - LETTERS TO THE EDITOR.

PMID- 18732235
TI  - Proposed Amendment to C.M.A. Constitution.

PMID- 18732236
TI  - In Memoriam.

PMID- 18732237
TI  - PUBLIC HEALTH REPORT.

PMID- 18732239
TI  - Moving Day-To 693 Sutter.

PMID- 18732238
TI  - Rehabilitation Aid to Needy Disabled-A Program for Improvement of Independent
      Function.

PMID- 18732240
TI  - More Than Provincial.

PMID- 18732241
TI  - In Memoriam.

PMID- 18732242
TI  - PUBLIC HEALTH REPORT.

PMID- 18732244
TI  - Physician Rights to Staff Membership.

PMID- 18732243
TI  - WOMAN'S AUXILIARY: WE HELP OUR OWN.

PMID- 18732245
TI  - Health Insurance for Federal Employees.

PMID- 18732246
TI  - Proposed Amendment to C.M.A. Constitution (Second Publication).

PMID- 18732247
TI  - In Memoriam.

PMID- 18732248
TI  - PUBLIC HEALTH REPORT.

PMID- 18732249
TI  - WOMAN'S AUXILIARY.

PMID- 18732251
TI  - Vendors of Doctor-Care.

PMID- 18732250
TI  - Whither Government?

PMID- 18732252
TI  - Six-Year Cancer Study to Be Conducted.

PMID- 18732253
TI  - In Memoriam.

PMID- 18732254
TI  - PUBLIC HEALTH REPORT.

PMID- 18732255
TI  - WOMAN'S AUXILIARY.
AB  - The following remarks are excerpts from an address by T. Eric Reynolds, M.D.,
      President of the California Medical Association, at a meeting of the Woman's
      Auxiliary to the California Medical Association, Santa Barbara, September, 1959.

PMID- 18732256
TI  - MEDICINE AT MID-CENTURY.

PMID- 18732258
TI  - Forand Time Again.

PMID- 18732257
TI  - A Study of C.M.A. Scientific and Educational Functions.

PMID- 18732259
TI  - Health Report.

PMID- 18732260
TI  - Recent Trends in Professional Liability Cases.

PMID- 18732262
TI  - PUBLIC HEALTH REPORT.

PMID- 18732261
TI  - In Memoriam.

PMID- 18732263
TI  - WOMAN'S AUXILIARY.

PMID- 18732265
TI  - C.M.A. ANNUAL REPORTS.

PMID- 18732264
TI  - Income Taxes-Deductibility of Entertainment Expenses.

PMID- 18732267
TI  - A Million Dollars for Medical Education.

PMID- 18732266
TI  - 8-METHOXYPSORALEN-A Short Review and Comment.
AB  - 8-Methoxypsoralen is a purified extract of the root ammi majus lynn, which was
      used in a crude form for centuries in the Middle East in the treatment of various
      skin diseases. In recent years it has been found that the purified extract, when
      taken internally, increases all skin responses to sunlight, including tanning.
      When too much drug is taken or when the patient is exposed to sunlight too long,
      the preliminary erythema may be painful, and blistering may occur. In some
      patients with vitiligo, islands of pigmentation appear around the hair follicles
      when the drug is taken, and in favorable cases these islands may coalesce to form
      continuous areas of pigmented skin. The drug has been found nontoxic, but
      successful treatment of vitiligo takes place in only a small proportion of
      patients. Promiscuous use of the drug for cosmetic tanning is to be deplored. The
      constant irritation of the skin due to the increased action of sunlight when the
      drug is used may possibly increase the incidence of sun-induced skin cancers.A
      topical preparation is available, which, when used with great care, may help to
      repigment small areas of vitiligo.

PMID- 18732268
TI  - Physicians and Population.

PMID- 18732270
TI  - In Memoriam.

PMID- 18732269
TI  - Physical Examinations for Physicians.

PMID- 18732272
TI  - WOMAN'S AUXILIARY.

PMID- 18732271
TI  - PUBLIC HEALTH REPORT.

PMID- 18732273
TI  - Tax Deductibility-The Status of Accident and Health Insurance Premiums.

PMID- 18732274
TI  - Pharmaceutical Advertising.

PMID- 18732275
TI  - The Podiatrist and Medicine.

PMID- 18732276
TI  - Warren L. Bostick, M.D., New C.M.A. President-Elect.

PMID- 18732277
TI  - In Memoriam.

PMID- 18732278
TI  - PUBLIC HEALTH REPORT.

PMID- 18732279
TI  - WOMAN'S AUXILIARY.

PMID- 18732281
TI  - Guides for Medical Education Efforts by the Drug Industry.

PMID- 18732280
TI  - Medicare Changes.

PMID- 18732283
TI  - Milestones.

PMID- 18732282
TI  - Periodic Paralysis Associated with Hyperthyroidism.

PMID- 18732284
TI  - LETTERS TO THE EDITOR.

PMID- 18732285
TI  - Public Relations.

PMID- 18732286
TI  - The California Medical Association Delegation to the A.M.A.

PMID- 18732287
TI  - The "Fiery Trial" of Private Practice-Report of the Commission on Medical
      Services.

PMID- 18732288
TI  - In Memoriam.

PMID- 18732290
TI  - The Doctor in the Middle.
AB  - The following letter, written by legal counsel for the California Medical
      Association in reply to a specific inquiry made by the medical insurance
      committee of a county medical society, bears upon a point of general interest to
      physicians.

PMID- 18732289
TI  - PUBLIC HEALTH REPORT.

PMID- 18732291
TI  - Deductibility of Traveling Expenses.

PMID- 18732292
TI  - Blood Alcohol Test-Legal Effect of Participation.

PMID- 18732293
TI  - WOMAN'S AUXILIARY: FAREWELL-AND HAIL!

PMID- 18732295
TI  - THE PSYCHODYNAMICS OF HYPERTENSION.
AB  - Psychotherapeutic study of patients with essential hypertension shows evidence of
      massive repression of unacceptable feelings in many areas of the personality,
      predominantly feelings of rage and hostility. It appears that in the mentation of
      the hypertensive person, rage not only risks the loss of affection and approval
      by others, but is unconsciously equated by him with murderous loss of self
      control. In addition, he characteristically has an inordinate fear of death.
      Intensive insight psychotherapy, when commenced early in a well-motivated
      patient, is very effective in the treatment of this disorder. As in any
      psychosomatic condition, the patient should be concomitantly treated by his
      general physician or by an internist.

PMID- 18732294
TI  - RHEUMATOID ARTHRITIS-Current Therapy and Medical Management.
AB  - Although no routinely effective therapy for patients with rheumatoid arthritis is
      available, certain established principles of management and a variety of
      medications do provide benefit. Conservative management programs may suffice in
      milder cases. Aspirin or other salicylates and physical therapy are the mainstays
      in such programs. The antimalarial drugs may be helpful in a small proportion of
      cases. Steroids have had beneficial effect rather consistently and, with the
      newer analogues, certain side effects have become less troublesome. The usual
      precautions with the use of these compounds must be observed as always.
      Chrysotherapy remains important in the treatment of severe cases, and its use
      should not be postponed until major destructive joint changes have occurred.

PMID- 18732297
TI  - Skin Cancer in Smallpox Vaccination Scars-A Report of Five Cases.

PMID- 18732296
TI  - CORNEAL CONTACT LENSES-Special Value in Severe Anisometropia in Children.
AB  - Careful selection of patients and skillful fitting result in a high rate of
      success with corneal contact lenses-over 96 per cent in 339 patients treated in
      the present series. The lenses were especially valuable in anisometropia in
      children (11 cases). Children can be taught to care for contact lenses and insert
      and remove them for themselves.

PMID- 18732298
TI  - The Governor's Committee.

PMID- 18732300
TI  - Transactions of the House of Delegates, Los Angeles, February 21-24, 1960.

PMID- 18732299
TI  - Positive Public Relations.

PMID- 18732302
TI  - In Memoriam.

PMID- 18732301
TI  - Proposed Constitutional Amendment.

PMID- 18732303
TI  - PUBLIC HEALTH REPORT.

PMID- 18732304
TI  - WOMAN'S AUXILIARY: COMMITTEES.

PMID- 18732305
TI  - INTESTINAL ADHESIONS-Present Status of Prevention and Treatment.
AB  - Although many treatments have been proposed for the prevention of intestinal
      adhesions, none has been completely effective. For bowel obstruction due to
      adhesions the initial approach should be conservative. If operation becomes
      necessary, the best results depend on avoidance of trauma and infection, division
      of adhesions with cautery, use of mesothelial grafts, instillation of
      intraperitoneal hyaluronidase and stimulation of early postoperative peristalsis.
      In the event of massive adhesions or failure of other treatment, intestinal
      plication is the treatment of choice.

PMID- 18732306
TI  - BASILAR ARTERY DISEASE-Clinical Manifestations.
AB  - Patients with basilar artery disease show their first symptoms by characteristic
      ischemic attacks. If the attending physician correctly diagnoses the condition
      and initiates anticoagulant therapy before a catastrophic episode occurs, there
      is reason to believe that the disease may be arrested temporarily.

PMID- 18732307
TI  - Health Services for the Elderly.

PMID- 18732308
TI  - Commission and Committee Appointments, April 23, 1960.

PMID- 18732309
TI  - In Memoriam.

PMID- 18732311
TI  - The A.M.A. 1960 Session.

PMID- 18732310
TI  - PUBLIC HEALTH REPORT.

PMID- 18732312
TI  - Actions of the A.M.A. House of Delegates.
AB  - This summary from the Executive Vice-President's office of the American Medical
      Association covers only a few of the many important subjects dealt with by the
      House and is not intended as a detailed report on all actions taken.

PMID- 18732313
TI  - In Memoriam.

PMID- 18732314
TI  - PUBLIC HEALTH REPORT.

PMID- 18732315
TI  - WOMAN'S AUXILIARY: A MESSAGE TO THE DOCTORS.

PMID- 18732317
TI  - Medicine and Allied Health Professions.

PMID- 18732316
TI  - AN APPROACH TO BILIARY TRACT OPERATIONS.
AB  - By changing the position of the patient and of the operating team and by using a
      right-angle incision, superb exposure of the right upper quadrant abdominal
      contents can be had with little or no retraction by human effort.

PMID- 18732318
TI  - The Malignant Effect of Premature, Mass Publicity Concerning Factors Causing
      Malignant Disease.

PMID- 18732319
TI  - In Memoriam.

PMID- 18732320
TI  - PUBLIC HEALTH REPORT.

PMID- 18732321
TI  - Old Age Medical Care Needs: A Comprehensive Medical Health Evaluation Program
      Proposed for Old Age Security Recipients.

PMID- 18732322
TI  - WOMAN'S AUXILIARY: THIRTY-SEVENTH ANNUAL MEETING, NATIONAL AUXILIARY.

PMID- 18732323
TI  - DISASTER MEDICAL CARE AND SHELTER-The Federal Program.
AB  - The role of the physician in event of natural disaster or overwhelming (perhaps
      nuclear) attack by an enemy is:To assist the layman in preparing to meet his own
      health needs in a disaster situation until organized health services can reach
      him. To prepare and plan for the provision of organized medical care when
      conditions permit. To extend his own capability to render medical care outside
      his normal specialty. To assist in the training of allied and professional health
      workers and laymen for specific mobilization assignments in health services.

PMID- 18732324
TI  - BACTERIAL AND CHEMICAL WARFARE-The Current Status.
AB  - For fourteen years public attention has been focused so sharply on atomic weapons
      as to lose sight of other, less spectacular but equally significant advances in
      the art of warfare. In the shadows cast by brilliant research in nuclear physics
      are hidden startling advances in the field of chemical and biological weapons.
      These weapons, as now developed, are not only capable of producing mass
      casualties quite comparable with those of atomic bombs, but they also possess
      certain advantages which may make them the weapons of choice for an unscrupulous
      enemy. If war should come, it is the medical profession which will have the sole
      responsibility for protecting the citizens of California against these weapons,
      and we can therefore delay no longer in acquainting ourselves with their
      potentialities and characteristics. In this task, we are working under two
      serious handicaps. The first is that our classical medical training affords
      little appreciation of the real danger, and the second is the cloak of secrecy
      surrounding the entire subject.

PMID- 18732325
TI  - PREPARATION FOR DISASTER IN CALIFORNIA.
AB  - THE OPERATIONAL PLAN FOR MEDICAL PREPAREDNESS IN CALIFORNIA IS DIVIDED INTO THREE
      MAIN DIVISIONS, VIZ: Expansion of existing medical facilities, augmentation of
      practicing health personnel, scope of service expected. Medical and health
      personnel and facilities will be expected to modify and adjust their care of
      casualties according to the situation present such as strategic warning, alert
      signal (yellow), take cover signal (red), and the post-attack period. This
      service is concerned with conservation of resources (human) and must do
      everything possible to return people to a status where they can help rebuild our
      nation.Supplies already obtained and stored throughout the state consist of first
      aid stations, emergency hospitals, blood procurement equipment, sanitation units.
      Over a half million first aiders and more than 96,000 home nurses have been
      trained by the local chapters of the American National Red Cross.

PMID- 18732326
TI  - FAT AND CARBOHYDRATE METABOLISM IN HUMANS-A Study of Nutritional and Hormonal
      Effects.
AB  - As an index to the rate of fat utilization in human subjects, the recovery of all
      radioactive carbon dioxide in the expired air was measured for one hour following
      intravenous injection of palmitate-1-C(14). In the normal fasted subject, about
      10 per cent of the injected dose was recovered, and the proportion was lowered to
      about 5 per cent by administration of glucose. With prolonged fasting, the
      recovery of radioactive carbon dioxide did not change, despite a rising
      concentration of fatty acids in the serum. This was interpreted as due to the
      development of a balance between increasing mobilization and oxidation and was
      thought to indicate increasing fatty acid oxidation. In chronic undernutrition
      and diabetes mellitus there was increased fatty acid oxidation due presumably to
      adaptation to a chronic increase in fat utilization for energy. Administration of
      human growth hormone did not increase fat oxidation but prevented the usual
      inhibition produced by glucose. This was interpreted to mean that growth hormone
      increases fat utilization only indirectly by inhibiting the usual preferential
      utilization of glucose over fat.

PMID- 18732327
TI  - THE GUILLAIN-BARRE DISEASE COMPLEX-An Analysis of the Disease with Therapeutic
      Suggestions and Report of 26 Cases.
AB  - The Guillain-Barre disease complex may result from a number of causes and have a
      wide variety of effects. The basic mechanism seems to be an immunizing or
      allergic reaction to many pathogens or their products, causing edema of the nerve
      roots in the spine, specifically about the meningeal covering. Resulting pressure
      on the axon causes nerve damage proportional to the severity and duration of
      pressure. Results in the 26 cases here reported and in other reports indicate
      that corticosteroids are the treatment of choice, the purpose being to reduce
      edema as promptly as possible. As might be expected, this therapy is of little
      value in the post-inflammatory stage of the disease, although prophylactic
      administration should continue for several months. Nerve and muscle
      rehabilitation are the chief aims of later treatment.

PMID- 18732328
TI  - A SIMPLE WAY TO DRAIN A SUBUNGUAL HEMATOMA.

PMID- 18732329
TI  - RABIES-Suggested Indications for Treatment of Persons After Exposure to
      Infection.

PMID- 18732330
TI  - POSTPARTUM PHLEBECTOMY.
AB  - Saphenous vein ligation and stripping was performed on 27 patients in the
      immediate postpartum period without complications. Doing the operation at this
      time saves time and money. Technically it is easier to do postpartum than during
      pregnancy, and the patients have less postoperative discomfort than is usual with
      phlebectomy at other times.

PMID- 18732332
TI  - Medical Television.

PMID- 18732331
TI  - A Case of Leptospirosis Ballum in California.

PMID- 18732333
TI  - In Memoriam.

PMID- 18732334
TI  - PUBLIC HEALTH REPORT.

PMID- 18732335
TI  - WOMAN'S AUXILIARY.

PMID- 18732336
TI  - Poliomyelitis.

PMID- 18732337
TI  - SALIVARY GLAND TUMORS.
AB  - In a review of a series of 248 salivary gland tumors, seen over a 28-year period,
      all pathologic material was brought up to date by reclassification according to
      more recent criteria and nomenclature. In parotid tumors, a probable lowered
      recurrence rate and a definite decrease in incidence of permanent facial nerve
      paralysis was found in the more recent cases in which the "Y" incision was used,
      with identification of the seventh nerve as it leaves the stylomastoid foramen.
      The five-year recurrence rate for primary mixed tumor was 8.3 per cent, and in
      recurrent cases it was found to be 18.1 per cent. Of 44 patients with malignant
      salivary gland tumors in all sites who were observed for five years or more, 32
      or 72.7 per cent survived five years.

PMID- 18732338
TI  - PSYCHIATRIC UNITS IN GENERAL HOSPITALS-Problems in Development and Efficient
      Operation.
AB  - An adequate 25-bed psychiatric unit can be housed in a wing of a general
      hospital. Even more important than physical facilities are competent personnel,
      to be headed by a chief psychiatrist and a psychiatric nurse supervisor, for the
      unit. Incorporating teaching facilities into the unit helps to integrate
      psychiatry into the other disciplines of medicine in a continuing educational
      program. Having psychiatric units in general hospitals enables many voluntary
      patients to be treated in early stages of the disorder, with a high proportion of
      recoveries. Medicolegal aspects and the lack of adequate coverage of mental
      disorders by voluntary prepayment health plans are serious problems in the
      economy of a unit. Improved hospital administration, expanded training programs,
      educational work by local mental health societies and modification of laws on
      malpractice and commitment will go far to help solve these problems.

PMID- 18732339
TI  - Chronic Disseminated Histiocytosis X-Eosinophilic Granuloma of Skin, Mucous
      Membrane and Bone.

PMID- 18732340
TI  - Relief of Canker Sores on Resumption of Cigarette Smoking.

PMID- 18732341
TI  - Relative Value Study.

PMID- 18732343
TI  - Cranberries et al.

PMID- 18732342
TI  - Cranberries et al.

PMID- 18732344
TI  - Cranberries et al.

PMID- 18732345
TI  - Federal-State Medical Care-The Expanded Program for Needy and Near-Needy Aged.

PMID- 18732347
TI  - PUBLIC HEALTH REPORT.

PMID- 18732346
TI  - In Memoriam.

PMID- 18732348
TI  - WOMAN'S AUXILIARY: ANOTHER WORTHWHILE PROJECT.

PMID- 18732349
TI  - A PROGRAM FOR MENTAL HYGIENE IN CALIFORNIA.
AB  - While the Department of Mental Hygiene cannot undertake to meet all the mental
      health needs of the citizens, it should make the best possible use of all its own
      resources, and at the same time help others to make the most of theirs. To these
      ends it should* Give encouragement and assistance to persons engaged in
      prevention of mental disorders, without trying to operate such services.*
      Encourage and help persons engaged in the preservation of the human strengths
      that increase resistance to mental breakdown, without trying to operate such
      services.* Encourage and help persons outside the department who diagnose, treat
      and rehabilitate patients with mental disorders if these services meet the
      requirements of modern psychiatric treatment.* Continue operating hospitals at
      current level of bed capacity, clinics and related services for diagnosis,
      treatment and rehabilitation, moving toward levels of service in keeping with
      modern psychiatric standards and the growing population of the state.* Continue
      research and training within the Department and assist others in such programs
      outside the Department.

PMID- 18732350
TI  - TRACHEOTOMY IN CHILDREN-A Controlled, Planned Emergency Procedure.
AB  - The value of tracheotomy as a life-saving operation has been increased greatly in
      recent years by a broadening of the indications for its use. It is made safer for
      the patient by performing it reasonably early, and, in any event, under planned
      emergency conditions. The first is made possible by experience and judgment in
      choosing the time, mainly from close observation of the patient; the second by
      preceding the operation with tracheal intubation. Meticulous post-operative care
      is of great importance.

PMID- 18732352
TI  - Mental Health in California.

PMID- 18732351
TI  - ISCHIECTOMY FOR PRESSURE SORES.
AB  - Ischiectomy with primary closure was carried out in five paraplegic patients with
      pressure sores. This operation, less extensive than the wide excision with full
      thickness graft that is now widely advocated, was successful in four of the five
      cases. In the fifth case none of the several attempts to heal the sores was in
      the least successful.

PMID- 18732353
TI  - Medical Expert Panels for Malpractice Cases-C.M.A. Liaison Committee with the
      State Bar of California.

PMID- 18732354
TI  - PUBLIC HEALTH REPORT.

PMID- 18732356
TI  - Evaluation of Industrial Disability.

PMID- 18732355
TI  - WOMAN'S AUXILIARY: FALL CONFERENCE.

PMID- 18732357
TI  - CHOLEDOCHOLITHIASIS-Correlation of Preoperative with Operative and Postoperative
      Data to Enhance Diagnostic Insight.
AB  - One hundred cases of common bile duct explorations were reviewed in an attempt to
      obtain information that might give insight into the diagnosis and definitive
      treatment of choledocholithiasis. Fifty of the hundred patients had common duct
      stones. Correlations were made between the incidence of choledocholithiasis as
      proved at operation, and the following factors: Kind and number of choledochal
      exploratory criteria used, the clinical diagnosis of common duct stones, and the
      pathologic features of gallbladders removed. The incidence of stones was
      statistically related to aging. The most frequent choledochal exploratory
      criteria were common duct dilatation or thickening (63 cases) and history of
      jaundice (50 cases). The most reliable single criterion in "diagnosing" common
      duct stones was palpable common or hepatic duct stones, the diagnosis having been
      correct in 15 of 17 such cases. The most reliable combination of criteria was a
      history of jaundice, plus palpable stones, with correct diagnosis in all such
      cases. The clinical diagnosis of choledocholithiasis was correct in only 17 per
      cent of cases. The correlation of the incidence of common duct stones with the
      degree of gallbladder disease-that is, acute or chronic-did not provide
      information that might be helpful in diagnosing choledocholithiasis. The
      incidence of proven retained common duct stones was 3 per cent, the non-fatal
      postoperative complication rate was 21 per cent and operative mortality was 1 per
      cent.

PMID- 18732359
TI  - Future Physician Recruitment.

PMID- 18732358
TI  - THE SIGNIFICANCE OF INFECTION IN ALLERGIC DISEASE-Its Influence on Diagnosis and
      Management.
AB  - The presence of infection in allergic disease produces a confused picture in
      which two different causative factors must be clearly separated by the physician
      if he is to treat the patient successfully. The effects of infection are not
      consistent. There are situations, as seen in infectious diseases, where symptoms
      of allergic disease are temporarily relieved and others where the infection may
      intensify or precipitate the allergic condition. It is likewise important to
      recognize the complications superimposed upon allergic disease by infection. In
      such cases, control of the infection is as dependent upon control of the allergy
      as it is upon antibiotics.

PMID- 18732360
TI  - LETTERS TO THE EDITOR.

PMID- 18732361
TI  - Proposed Constitutional Amendment (First Publication).

PMID- 18732362
TI  - In Memoriam.

PMID- 18732363
TI  - PUBLIC HEALTH REPORT.

PMID- 18732364
TI  - Implied Warranty of a New Medicinal Agent.

PMID- 18732365
TI  - Limited Liability for Directions to Use a Medicine in an "Acceptable" Way.

PMID- 18732366
TI  - PORTACAVAL SHUNT IN PATIENTS WITH CIRRHOSIS-After-Effects of the Operation.
AB  - The subject of the indications for operation for portacaval shunt bristles with
      problems to which a satisfactory answer cannot yet be given. I have discussed
      those events which supervene after a portacaval shunt which, in the present state
      of knowledge, has been directed as proper and well-intentioned therapy. It is
      against the knowledge of such post-shunt events and the complexity of their
      management, as well as the success of the operation and the risk of mortality,
      that one must balance the indications for surgery. This is particularly pertinent
      to the application of prophylactic shunt surgery now under consideration.

PMID- 18732367
TI  - C.P.S. - Blue Shield.

PMID- 18732368
TI  - In Memoriam.

PMID- 18732369
TI  - PUBLIC HEALTH REPORT.

PMID- 18732371
TI  - Legislative Time Again.

PMID- 18732370
TI  - WOMAN'S AUXILIARY: AUXILIARIES' CHRISTMAS ACTIVITIES.

PMID- 18732373
TI  - In Memoriam.

PMID- 18732372
TI  - LETTERS TO THE EDITOR.

PMID- 18732374
TI  - PUBLIC HEALTH REPORT.

PMID- 18732375
TI  - WOMAN'S AUXILIARY: NATIONAL FALL CONFERENCE.

PMID- 18732376
TI  - TRAUMA OR STRAIN AND HEART DISEASE-Causal Relationship.
AB  - Myocardial infarction and coronary insufficiency are the common conditions
      involved in workmen's compensation cases based on allegations of cardiac injury.
      Since coronary disease tends to be a progressive process, punctuated by sudden
      accidents, it is difficult to determine when a given stress at work may have had
      a significant effect in producing an infarction. Though there are gaps in our
      knowledge, considerable information is available indicating the way in which
      effort or stress may produce a myocardial infarction. Certain states have taken
      steps to develop more uniformity of medical opinion regarding causal relationship
      of stress to heart disease, and in other ways have attempted to improve the
      application of workmen's compensation laws in an attempt to provide fair and
      prompt compensation to those injured by their work but to discourage abuses of
      these laws.

PMID- 18732377
TI  - CARDIAC INJURY IN BODILY TRAUMA-A Clinical Study.
AB  - Involvement of the heart in bodily trauma occurs in a variable incidence. It is
      most frequently observed secondary to chest injuries. Because generalized bodily
      trauma can produce cardiac damage, the examination of the cardiovascular system
      is indicated and justified in cases of bodily injury.

PMID- 18732379
TI  - California Physician Placement Service.

PMID- 18732378
TI  - CLINICAL EXPERIENCE WITH FLUETHER ANESTHESIA.
AB  - Fluether, an azeotropic mixture of two volumes of Fluothane(R) and one volume of
      diethyl ether, will provide satisfactory surgical anesthesia in a range of vapor
      concentration from 0.5 per cent v/v to 4.0 per cent v/v. The agent was used in
      all age groups and in all patient physical states in approximately a thousand
      cases. To date there have appeared no contraindications to the use of fluether
      anesthesia. Bradycardia is common during induction but is easily reversible by
      use of belladonna compounds. During maintenance of anesthesia, significant
      muscular relaxation is provided, without evidence of electrocortical depression.
      Respiratory depression accompanies a maintenance level of anesthesia. Recovery
      after anesthesia with fluether is rapid but tranquil. Considerable analgesia
      persists during recovery.

PMID- 18732380
TI  - In Memoriam.

PMID- 18732381
TI  - PUBLIC HEALTH REPORT.

PMID- 18732382
TI  - Children, the Victims of Fragmentation Of Health Services.

PMID- 18732383
TI  - What Constitutes an Adequate Exploration in the Abdomen.

PMID- 18732384
TI  - MULTIPLE LABORATORY EVALUATION OF THE REITER PROTEIN COMPLEMENT FIXATION METHOD.
AB  - Duplicate Reiter protein complement fixation tests were carried out on different
      days at the UCLA laboratory on 636 specimens entailing diagnostic problems.
      Results were in agreement in 94.2 per cent of cases.A comparison of the results
      obtained with the first RPCF test carried out on 639 diagnostic problem specimens
      submitted to four Los Angeles laboratories showed disagreement ranging from 10 to
      13 per cent.Agreement between RPCF and TPI results in each of the four
      laboratories ranged from 81.2 to 82.7 per cent.A greater correlation was obtained
      between RPCF and TPI results than between TPI and STS or RPCF and STS. In the
      presence of nonreactive RPCF tests, from 5.6 to 7.1 per cent of the specimens
      tested in each laboratory were reactive to VDRL and TPI tests. Nonreactive VDRL
      and reactive TPI results ranged from 7.2 to 8.3 per cent of the specimens tested.
      In the presence of reactive TPI and RPCF results, 5.5 to 6.4 per cent of the
      specimens tested in each laboratory showed nonreactive VDRL tests.Twenty-nine or
      4.6 per cent of 625 specimens tested showed nonreactive VDRL, reactive
      cardiolipin Kolmer and reactive TPI tests.Of the weakly reactive RPCF, VDRL or
      cardiolipin Kolmer tests, a higher percentage of the RPCF results gave reactive
      TPI tests than did either the VDRL or cardiolipin Kolmer procedures. The number
      of specimens showing discrepant RPCF results upon being retested in the four
      laboratories ranged from 33 to 68. Reactive TPI tests on those specimens ranged
      from 30.3 per cent to 54.4 per cent.

PMID- 18732385
TI  - CORONARY ARTERIOGRAPHY.
AB  - The rapid injection of opaque media through a large bore, closed-end, side-hole
      catheter positioned adjacent to the sinuses of Valsalva reliably opacifies the
      coronary arteries. The potential toxicity of a rapidly introduced large volume of
      contrast agent and the necessity of peripheral arteriotomy are drawbacks of this
      procedure. Such innovations as loop-ended catheters, balloon occlusion of the
      aorta, percutaneous arterial catheterization and acetylcholine cardiac arrest
      have been introduced as attempts are made to increase the reliability and safety
      of coronary arteriography.

PMID- 18732386
TI  - A Perineo-Abdominal Approach for Resection of a Presacral Tumor.

PMID- 18732387
TI  - A Plan of Our Own.

PMID- 18732389
TI  - In Memoriam.

PMID- 18732388
TI  - Maternal Mortality Reports, C.M.A. Committee on Maternal and Child Care.
AB  - The case reports come from the files of the State Department of Public Health
      which, together with the California Medical Association, now sponsors the
      statewide studies of all maternal mortalities. Selected Cases are to be presented
      here from time to time as a matter of interest and illumination to all physicians
      concerned with the practice of obstetrics. It is hoped that a review of such
      significant cases will help to improve the welfare of future California mothers.

PMID- 18732391
TI  - WOMAN'S AUXILIARY: SUMMING UP.

PMID- 18732390
TI  - PUBLIC HEALTH REPORT.

PMID- 18732392
TI  - LETTERS TO THE EDITOR.

PMID- 18732393
TI  - C.P.S.-Blue Shield.

PMID- 18732394
TI  - Control of Cancer Quackery.

PMID- 18732396
TI  - Notes on Medical Liability.

PMID- 18732395
TI  - $317,000 Settlement in Malpractice Case.

PMID- 18732397
TI  - ALMOST WITHIN OUR GRASP.

PMID- 18732398
TI  - RADIATION: MEDICAL DIAGNOSTIC USES.
AB  - Use of radiologic procedures in diagnosis now contributes a significant dose of
      ionizing radiation to our population. Whether this presents a real risk to the
      health of the present and future population cannot be determined with certainty
      from evidence available at this time. Hence, it appears proper to keep the dose
      to every patient as low as practical consistent with good medical practice. The
      average dose can be significantly reduced by having more physicians apply the
      known techniques for minimizing the exposure to the patient. The medical
      profession has a direct professional concern for the actual or potential risk of
      damage resulting from the radiation that patients are exposed to during
      diagnostic x-ray procedures, since these procedures constitute the largest single
      man-made source of genetically significant radiation our population is now
      exposed to. It is important to distinguish two distinctly different types of
      radiation effects-somatic effect, in which the damage affects the health of the
      person irradiated, and genetic effect that is capable of producing constitutional
      defects in future progeny over many generations.

PMID- 18732399
TI  - DIGITALIS IN OPEN HEART OPERATIONS.
AB  - In addition to the usually accepted indications for digitalis therapy, we believe
      there is a group of patients, not having heart failure, who would benefit from
      digitalis in connection with open operations on the heart. This group includes
      all adults, all with the tetralogy of Fallot, and all with high pressure
      ventricular septal defects. Digitalis preparations can be given in the usual
      digitalizing doses several days before operation to insure the presence of some
      glycosides at the end of the operation when cardiopulmonary by-pass is
      discontinued. An additional maintenance dose can be given by the anesthetist at
      the time of completion of cardiopulmonary by-pass and another dose the evening of
      operation. If during the immediate postoperative period supraventricular
      arrhythmia occurs, particularly tachycardia, the ouabain test is extremely useful
      and safe in determining whether or not more digitalis is needed.

PMID- 18732400
TI  - Best Foot Forward.

PMID- 18732401
TI  - Substandard Clinical Laboratories.

PMID- 18732402
TI  - PUBLIC HEALTH REPORT.

PMID- 18732403
TI  - Suit Against Physicians for Hospital Medical Staff Activities.

PMID- 18732404
TI  - FROM WHERE WE ARE TO WHERE WE SHOULD BE.

PMID- 18732405
TI  - CIRRHOSIS OF THE LIVER-Clinical Course in 2,377 Patients at San Francisco General
      Hospital.
AB  - The records of 2,377 patients with Laennec's cirrhosis were reviewed for the
      period 1947-1957. The chief presenting symptom was ascites in 46 per cent,
      bleeding in 23 per cent, coma in 18 per cent, jaundice in 9 per cent, and both
      jaundice and ascites in 4 per cent. Nearly half of the patients died during the
      period under study-one-third from hepatic failure, one-third from
      gastrointestinal bleeding, and one-third from other causes, most of which were
      related to alcoholism.Massive gastrointestinal bleeding occurred in 21 per cent
      of the patients at some time in their clinical course, and in the 10 per cent of
      these in whom ulcer was demonstrated, one-fifth died as a result of the
      hemorrhage. Of those presumed to be bleeding from esophageal varices, 64 per cent
      died at the first hemorrhage and 10 per cent at subsequent hemorrhages; 85 per
      cent of all those who bled from varices were dead at the end of one year, and 91
      per cent were dead at the end of three years. The survival curve of a group of
      patients who bled once and were good operative risks but had received no
      operative treatment was compared to the survival curve for entire group who
      survived the first hemorrhage. The three-year survival in the good risk group was
      47 per cent; for the group as a whole it was 30 per cent. The difference in
      mortality rate was primarily due to an increased number of deaths from hepatic
      failure in the combined group, whereas 60 per cent of the good risk group died of
      recurrent gastrointestinal hemorrhage. As 86 per cent of those who were to die of
      gastrointestinal bleeding did so at the first hemorrhage, it was concluded that
      any decided improvement in the salvage rate achievable by operation must come
      from some means of diagnostic forecast of the likelihood of bleeding, with resort
      to prophylactic operation in such cases.

PMID- 18732407
TI  - An Important Milestone.

PMID- 18732406
TI  - OTOTOXIC ANTIBIOTICS.
AB  - Shortly after the introduction of streptomycin and dihydrostreptomycin in the
      treatment of tuberculosis, irreversible perceptive hearing losses were noted as a
      side effect. Although hearing loss became less of a problem when reduced dosage
      schedules were adopted, the more widespread use of these drugs, often in
      combinations with other antibiotics, in nontuberculous disease has caused an
      increase in hearing loss in the last few years. Neomycin and kanamycin share this
      ototoxic property. Widespread use of these drugs is resulting in loss of hearing
      in a significant number of cases.

PMID- 18732409
TI  - Omer W. Wheeler, M.D., C.M.A. President-Elect.

PMID- 18732408
TI  - Well Done.

PMID- 18732410
TI  - Maternal Mortality Reports-Case 3, C.M.A. Committee on Maternal and Child Care.
AB  - These case reports are taken from the files of the State Department of Public
      Health which, together with the California Medical Association, now sponsors the
      statewide studies of all maternal mortalities. Selected cases are here presented
      from time to time as a matter of interest and illumination to all physicians
      concerned with the practice of obstetrics. They are prepared by the Committee on
      Maternal and Child Care. It is hoped that a review of such significant cases will
      help to improve the welfare of future California mothers.

PMID- 18732411
TI  - In Memoriam.

PMID- 18732412
TI  - PUBLIC HEALTH REPORT.

PMID- 18732414
TI  - Seminar Expenses.

PMID- 18732413
TI  - WOMAN'S AUXILIARY: MEDICINE FOR YOU IN 1961-62.

PMID- 18732415
TI  - Voices for Medicine.

PMID- 18732416
TI  - Congress on Medical Quackery.

PMID- 18732417
TI  - The Gemini: C.M.A. and C.P.S.

PMID- 18732418
TI  - Proposed Constitutional Amendments.

PMID- 18732419
TI  - In Memoriam.

PMID- 18732420
TI  - PUBLIC HEALTH REPORT.

PMID- 18732421
TI  - WOMAN'S AUXILIARY: MEMBERSHIP.

PMID- 18732422
TI  - LETTERS TO THE EDITOR.

PMID- 18732423
TI  - LETTERS TO THE EDITOR.

PMID- 18732424
TI  - THE PREVENTION OF LUNG CANCER-Applications of Some Current Theories.
AB  - The rapid increase in the incidence of bronchogenic carcinoma, the difficulties
      in early diagnosis and the infrequency of successful treatment emphasize the
      importance of attempts at its prevention. Much has been learned regarding the
      role of a variety of environmental factors in the genesis of this disease,
      although further studies are to be desired. The complete elimination of exposures
      to excessive irradiation or the inhalation of radioactive substances, to
      inorganic, organic or animate particles which may be responsible for chronic
      pulmonary diseases, and especially to automobile exhaust and cigarette smoke,
      occupational irritating or carcinogenic air pollutants and other predisposing
      conditions may require extensive changes in industry, government and society. A
      number of practical personal precautions are available, however, which may
      greatly reduce the hazard for the individual observing them.

PMID- 18732426
TI  - "Cadillac" Medicine.

PMID- 18732425
TI  - The A.M.A. Meeting.

PMID- 18732427
TI  - In Memoriam.

PMID- 18732429
TI  - PUBLIC HEALTH REPORT.

PMID- 18732428
TI  - Maternal Mortality Reports-Case 4, C.M.A. Committee on Maternal and Child Care.
AB  - These case reports are taken from the files of the State Department of Public
      Health which, together with the California Medical Association, now sponsors the
      statewide studies of all maternal mortalities. Selected cases are here presented
      from time to time as a matter of interest and illumination to all physicians
      concerned with the practice of obstetrics. They are prepared by the Committee on
      Maternal and Child Care. It is hoped that a review of such significant cases will
      help to improve the welfare of future California mothers.

PMID- 18732430
TI  - WOMAN'S AUXILIARY.

PMID- 18732431
TI  - C.P.S.-Its Strengths and Weaknesses.
AB  - The following, a supplement to the annual report of the Board of Trustees of
      California Physicians' Service that was published in the March 1961 issue of
      California Medicine, was delivered at the 1961 Annual Session of the House of
      Delegates by Dr. John G. Morrison, chairman of the board.

PMID- 18732432
TI  - Tumor Boards in California-The 1961-1962 Approved List.

PMID- 18732433
TI  - Traditional Physician-Patient Relationship-Changes Due to the Third Party.

PMID- 18732434
TI  - ASCARIASIS.
AB  - Ascaris infestations may be found in California, particularly in patients who
      have migrated from endemic regions. Clinical manifestations include vague
      abdominal pains, unexplained fever, anemia, malaise and upper respiratory tract
      infections. Intestinal obstruction and infections are among the severe
      complications that can occur. Diagnosis is made by the observation of worms or
      ova in the feces, and occasionally by roentgenographic manifestations.

PMID- 18732435
TI  - REFRACTORY HYPOTENSION-Diagnosis and Management in Surgical Patients.
AB  - Refractory hypotension is circulatory collapse of obscure cause which occurs in
      surgical patients who are thought to have a normal blood volume but in whom
      adequate circulation cannot be maintained. Such patients are usually treated
      empirically by the administration of intravenous vasopressor agents, and the
      mortality rate is relatively high.A specific diagnosis of the underlying cause
      for the refractory hypotension can be made by thorough clinical evaluation.
      Specific treatment aimed at correcting the underlying cause of the vascular
      collapse will lower the mortality rate in this serious type of circulatory
      failure.

PMID- 18732436
TI  - THE SJOGREN-MIKULICZ SYNDROME-Its Relationship to Connective Tissue Disorders.
AB  - Sjogren-Mikulicz syndrome, formerly thought rare, is recognized with increasing
      frequency, especially in middle-aged and elderly women. Often in the past,
      because of the peculiar swelling of the parotid gland which is a feature of the
      disease, the gland was removed on suspicion of cancer. New tests can identify
      cases in which the swelling is a part of the Sjogren-Mikulicz syndrome. In those
      cases the enlargement may disappear spontaneously or after treatment with
      corticosteroids. The tests consist chiefly of examining both the quality and the
      quantity of tears secreted; and in some cases biopsy of the gland may be
      necessary. The syndrome appears so often together with rheumatoid arthritis and
      related diseases as to give indication that it may be related etiologically. The
      cause is unknown. One possibility is that the patients form antibodies to their
      own glandular products, which destroy those products.

PMID- 18732438
TI  - Kerr-Mills or King-Anderson?

PMID- 18732437
TI  - MILK LET-DOWN-The Use of Intranasal Oxytocin for Nursing Mothers.
AB  - A study was carried out to determine whether intranasal spraying with a solution
      of oxytocin was an effective way to increase flow of milk in mothers who wished
      to breast-feed their babies.A hundred such women were given the drug
      intramuscularly for two days before they were to begin nursing. Then
      administration by that means was discontinued and 50 of the hundred were given
      oxytocin nasal spray kits for use at home. In general the patients receiving the
      spray kits were those who were apprehensive about sufficient lactation, those who
      had had previous difficulty and those who had flat, inverted or tender nipples.
      Results were not much different between the 50 women who used the spray and the
      50 controls, but since the former group included the "difficult" cases, some
      benefit may be attributed to the aerosol therapy. Ninety per cent of those who
      used it said they would be willing to use it again.

PMID- 18732439
TI  - Health Security, American Style.

PMID- 18732440
TI  - In Memoriam.

PMID- 18732441
TI  - PUBLIC HEALTH REPORT.

PMID- 18732442
TI  - WOMAN'S AUXILIARY: THE PHYSICIAN'S WIFE AND LEGISLATION.

PMID- 18732443
TI  - Data on Aging.
AB  - Federal payment for hospitalization and partial medical care of certain citizens
      65 and over is proposed in H.R. 4222. There are several important aspects of this
      proposed legislation which merit consideration, notably (1) How great is the
      actual need? and (2) Who would actually be covered by the proposed measure?1. The
      need for subsidized hospitalization and medical care is believed to be distinctly
      limited. A national study of the total life situation of those 65 and over (by
      Wiggins and Schoeck) showed that 90 per cent of the respondents reported no unmet
      medical needs of which they were aware. About 96 per cent reported no medical
      debts. This would leave presumably 4 per cent with such debts.2. The proposed
      legislation would cover those eligible for benefits under the Social Security Act
      and the Railroad Retirement Act, but not other elderly persons. The Wiggins
      Schoeck Report has been bitterly assailed by supporters of H.R. 4222 as being
      nonrepresentative and incomplete. Its authors (in a recent letter to Science)
      point out that it is indeed representative of the older population currently
      designated in H.R. 4222, and that it intentionally omitted those segments which
      would not be covered by H.R. 4222. In other words the data on needs of elderly
      persons as uncovered by Wiggins and Schoeck is pertinent to the legislation at
      hand. For this reason it is believed that physicians will be interested in
      reading the reply of these authors to the criticisms of their survey.With the
      permission of Science and of the authors, it is reprinted herewith.

PMID- 18732444
TI  - Resolution on C.P.S.

PMID- 18732445
TI  - STAFFING RATIOS IN A REHABILITATION PROGRAM.
AB  - Staffing ratios for professional personnel functioning in an intensive physical
      rehabilitation program at Rancho Los Amigos Hospital, representing experience
      with treatment of patients with severe physical disabilities on the one hand and
      budget pressures and procedures on the other, are as follows:Physician to
      patients..... 1:33Nursing service per patient per day (including registered
      nurse, licensed vocational nurse, attendant).....4 hoursPhysical therapy to
      patients..... 1:7Occupational therapy to patients.... 1:14Medical social service
      to patients.... 1:35Psychology or vocational counselor to patients (needing
      service)..... 1:35.

PMID- 18732446
TI  - The Newer Research.

PMID- 18732447
TI  - Who Sets the Standards?

PMID- 18732448
TI  - In Memoriam.

PMID- 18732449
TI  - Occupational Medicine Today.

PMID- 18732450
TI  - Maternal Mortality Reports-Case 5, C.M.A. Committee on Maternal and Child Care.
AB  - These case reports are taken from the files of the State Department of Public
      Health which, together with the California Medical Association, now sponsors the
      statewide studies of all maternal mortalities. Selected cases are here presented
      from time to time as a matter of interest and illumination to all physicians
      concerned with the practice of obstetrics. They are prepared by the Committee on
      Maternal and Child Care. It is hoped that a review of such significant cases will
      help to improve the welfare of future California mothers.

PMID- 18732451
TI  - Tissue Committee of a Hospital Medical Staff, C.M.A. Medical Review and Advisory
      Board.

PMID- 18732452
TI  - PUBLIC HEALTH REPORT.

PMID- 18732453
TI  - WOMAN'S AUXILIARY: HEALTH CAREERS.

PMID- 18732455
TI  - Well Guided Is Twice Driven.

PMID- 18732454
TI  - Discipline-Voluntary or Mandatory?

PMID- 18732456
TI  - Proposed Amendments to the Constitution.

PMID- 18732457
TI  - Proposed By-Law Amendments.

PMID- 18732459
TI  - PUBLIC HEALTH REPORT.

PMID- 18732458
TI  - Relationship of Occupational Medicine to Private Practice.

PMID- 18732460
TI  - In Memoriam.

PMID- 18732462
TI  - WOMAN'S AUXILIARY.

PMID- 18732461
TI  - Howard Christian Naffziger 1884-1961.

PMID- 18732463
TI  - The California Academy of General Practice-Its Objectives and Development.

PMID- 18732464
TI  - Costs of Hospitalization-A Report by the Bureau of Research and Planning.

PMID- 18732465
TI  - The Informed Surgical Consent-Report by the Joint California Medical Association
      California Hospital Association Medicolegal Education Committee.

PMID- 18732467
TI  - A.M.A. Policies Some Questions Raised, and Some Answers.

PMID- 18732466
TI  - An Item of Socialism.

PMID- 18732468
TI  - VOCAL NODULES-A High-Speed Photographic Analysis: Notes on Treatment.
AB  - Vocal nodules are benign tumefactions on the vocal cords due to excessive or
      improper use of the voice. They vary in size, shape, location and histologic
      composition and are essentially a clinical rather than a pathologic entity.High
      speed motion pictures at 5,000 frames per second revealed that they disturb the
      normal vibratory pattern in the same manner as benign tumors of the vocal cords
      generally. Treatment consists of vocal rest, vocal reeducation, and surgical
      operation, singly or in combination.

PMID- 18732469
TI  - Medicine's Representative.

PMID- 18732471
TI  - PUBLIC HEALTH REPORT.

PMID- 18732470
TI  - Your Plan for Survival.

PMID- 18732473
TI  - In Memoriam.

PMID- 18732472
TI  - Are You Up-to-Date?

PMID- 18732474
TI  - Physician Supply in California-Report by the Bureau of Research and Planning.

PMID- 18732476
TI  - Time for Political Action.

PMID- 18732475
TI  - Administration of Blood By Registered Nurses-Joint Statement by California
      Medical Association, California Hospital Association and California Nurses'
      Association.
AB  - After several years of favorable experience with registered nurses giving
      intravenous injections of fluids under the criteria set out in a joint statement
      by the California Medical Association, the California Hospital Association and
      the California Nurses' Association, it was proposed that it would be appropriate
      for registered nurses to administer blood. Careful study of current experience in
      various places with registered nurses giving blood transfusions convinced a joint
      committee that it recommend the adoption of the following statement which was
      approved by the associations indicated.

PMID- 18732477
TI  - The Third Man Theme.

PMID- 18732478
TI  - Standing Orders-Are You Liable?

PMID- 18732479
TI  - In Memoriam.

PMID- 18732480
TI  - PUBLIC HEALTH REPORT.

PMID- 18732481
TI  - WOMAN'S AUXILIARY.

PMID- 18732482
TI  - LETTERS TO THE EDITOR.

PMID- 18732483
TI  - Vitamin D Intoxication.

PMID- 18732484
TI  - Medical Aid to the Aged.

PMID- 18732486
TI  - The Rural Occupational Health Paradox.

PMID- 18732485
TI  - Pork Barrels and Health.

PMID- 18732487
TI  - In Memoriam.

PMID- 18732489
TI  - Proposed Amendments to the Constitution.

PMID- 18732488
TI  - PUBLIC HEALTH REPORT.

PMID- 18732491
TI  - WOMAN'S AUXILIARY: PROGRESS FOR A.M.A.-E.R.F.

PMID- 18732490
TI  - Proposed By-Laws Amendments.

PMID- 18732492
TI  - REFLECTIONS ON HYSTERECTOMY.
AB  - Except for childbearing, the uterus is not necessary in the body economy. It is
      subject to many troubles, many of which interfere with the patient's enjoyment of
      life, and some endanger life seriously. In view of great improvement in mortality
      and morbidity in the operation of hysterectomy, indications should be extended
      for this operation, taking this lessened danger into account.

PMID- 18732493
TI  - THE BLUE SHIELD CONCEPT.

PMID- 18732495
TI  - Mental Hygiene.

PMID- 18732494
TI  - CARCINOMA OF THE EYELID TREATED BY IRRADIATION-Analysis of 157 Primary and 22
      Recurrent Cases.
AB  - The eyelid is a frequent site for skin cancers of the face. Its location presents
      certain special problems in treatment from a cosmetic and functional standpoint.
      If untreated, a major deformity with possible loss of sight can result. This
      paper is a report of our treatment with irradiation of 157 primary tumors and 22
      recurrent tumors. In 98 per cent of patients there was control of the tumor for
      more than five years and a good cosmetic and functional result.

PMID- 18732496
TI  - C.M.A.'s First Purpose.

PMID- 18732498
TI  - Continuing Education and Scientific Activities: Some Abstracts of the Report of
      the C.M.A. Ad Hoc Committee on Continuing Education and Scientific Activities,
      Appointed by the Council, September 4, 1959.
AB  - The report from which the material here presented was abstracted was approved in
      principle by the Council and is now being studied as to detail by several
      committees of the C.M.A. and must be acted upon by the Council and the House of
      Delegates before final implementation.

PMID- 18732497
TI  - Socialized Health-A Tragic British Experiment.

PMID- 18732499
TI  - "Minor" Help in Emergencies.

PMID- 18732501
TI  - In Memoriam.

PMID- 18732500
TI  - In Memoriam: Samuel J. McClendon.

PMID- 18732502
TI  - PUBLIC HEALTH REPORT.

PMID- 18732503
TI  - Lapses of Consciousness Reportable as Epilepsy.
AB  - The following statement from the California Medical Association Traffic Safety
      Committee is endorsed by the C.M.A. Council and the State Department of Public
      Health.

PMID- 18732504
TI  - Old Age Assistance: A Report by the Bureau of Research and Planning.
AB  - What are some of the reasons why older persons become eligible for Old Age
      Assistance in California?How many become eligible because of medical care
      needs?This Report of the Bureau of Research and Planning draws upon recently
      published data of the State Department of Social Welfare and presents statistics
      covering a recent one-year period.

PMID- 18732505
TI  - The A.M.A. Education and Research Foundation.

PMID- 18732506
TI  - GASTRODUODENAL HEMORRHAGE: SURGICAL MANAGEMENT.
AB  - Two thousand five hundred forty-five cases of upper gastrointestinal tract
      hemorrhage were studied especially with a view to determining the indications for
      urgent surgical treatment. Decisions as to whether and when to operate were as
      follows:Immediate operation for patients over 50 years with a good history of
      ulcer and a severe initial bleed. Operation after the first repetition of
      bleeding in patients (1) over 50 with a good history and a mild initial bleed,
      (2) over 50 with inconclusive history but severe initial bleed, (3) under 50 with
      a good history and a severe initial bleed. In all other cases, operation was used
      only if conservative treatment failed. Absolute indications for operation were
      (a) association with perforation, (b) association with stenosis, (c) persistence
      of severe ulcer pain after hemorrhage, (d) continuous bleeding. Since operation
      is to be avoided if possible in cases of esophagitis, erosive gastritis and small
      acute or subacute ulcers, emergency gastroscopy has valuable uses. Where
      operation is deemed necessary and no obvious lesion found at laparotomy, blind
      gastrectomy appears to be the most satisfactory procedure. The mortality rate
      associated with upper gastrointestinal tract bleeding in patients less than 60
      years of age was low (2.5 per cent). Even in cases in which operation was
      required, it was 6.2 per cent. Over 60 years the mortality rises steeply with
      increasing age, and in cases of operation the rise is even steeper. By using the
      methods of selection the overall mortality rate was appreciably reduced.

PMID- 18732507
TI  - TETANUS PROPHYLAXIS IN THE UNIMMUNIZED-Administration of Oxytetracycline and
      Intradermal Toxoid, with Restricted Use of Tetanus Antitoxin.
AB  - Prophylactic tetanus antitoxin is ineffective in the prevention of experimental
      tetanus. That this may be true clinically is indicated by the fact that there are
      increasing numbers of cases of tetanus in humans after prophylactic tetanus
      antitoxin. Despite this known ineffectiveness and the high rate of reaction to
      antitoxin (5 per cent), many physicians continue to use it prophylactically,
      apparently for medical legal reasons. Since tetanus in civilian wounds is so
      rare, occurring approximately once in every million wounds, the routine use of
      tetanus antitoxin will probably cause more harm than good. It has been
      demonstrated experimentally that oxytetracycline is the most effective
      antimicrobial in the prevention of tetanus. It is, therefore, believed that
      adequate tetanus prophylaxis may be obtained by meticulous debridement and
      cleansing of the wound, by the administration of 1 gm. oxytetracycline daily for
      five days, and by intradermal administration of tetanus toxoid on the first,
      fourth and seventh days. Tetanus antitoxin is not given unless contaminated
      wounds have ben neglected for eight hours or more. In these instances, 15,000
      units or more of tetanus antitoxin is given. Tetanus toxoid remains the best
      wound prophylaxis and greater emphasis should be placed on immunizing entire
      populations.

PMID- 18732508
TI  - Medical Student Loans.

PMID- 18732509
TI  - Summitmanship.

PMID- 18732510
TI  - In Memoriam.

PMID- 18732511
TI  - "Release for Work,".

PMID- 18732512
TI  - PUBLIC HEALTH REPORT.

PMID- 18732513
TI  - Professional Corporation Proposals.

PMID- 18732514
TI  - Cancer: Unproven Methods of Diagnosis and Treatment.

PMID- 18732516
TI  - C.M.A. Organizational Activities.

PMID- 18732515
TI  - Public Relations and Performance.

PMID- 18732517
TI  - THE RESPONSIBILITIES OF EXCELLENCE.

PMID- 18732518
TI  - SCUBA DIVING AND THE CALIFORNIA PHYSICIAN.

PMID- 18732520
TI  - Green Light.

PMID- 18732519
TI  - HUMAN DURAL HOMOGRAFTS-Freeze-Dried Human Dura Mater for Closure of Dural
      Defects.
AB  - Freeze-dried human dura mater homograft has proved a highly successful, readily
      available and conveniently stored material for closure of dural defects. The
      material was used in three patients with good results as appraised after
      observation for periods of from two months to two years after operation. The
      freeze-dried dural homograft offers certain advantages over plastic implants,
      with regard to tissue acceptance by the host and more physiologic tissue
      response.

PMID- 18732521
TI  - Another First.

PMID- 18732522
TI  - Osteopathic Unification.

PMID- 18732523
TI  - New Law Requiring Medical Supervision-For California's Agricultural Workers Using
      Organophosphorous Pesticides.

PMID- 18732524
TI  - In Memoriam.

PMID- 18732525
TI  - PUBLIC HEALTH REPORT.

PMID- 18732526
TI  - Playing Politics with the Aged.

PMID- 18732527
TI  - SPORADIC ACUTE GLOMERULONEPHRITIS IN ADULTS.
AB  - Nineteen adults who had acute glomerulonephritis were reviewed with respect to
      the clinical course and long-term follow-up. The age range was from 17 to 55
      years. Only one patient died during the acute episode. In 11 cases, onset
      occurred between November and January and 15 of the patients had a known
      respiratory tract infection three to 30 days before the onset. The most important
      symptoms noted were weight gain, edema, dyspnea, oliguria and red or smoky urine.
      The most prominent physical signs were elevated blood pressure, edema,
      abnormalities in the chest and fever of over 100 degrees F. Fifteen patients
      showed roentgen evidence of pulmonary vascular congestion, pleural effusion,
      cardiomegaly, pneumonia or a combination of these abnormalities. All the patients
      had proteinuria and red blood cells in the urine, and half of them had red blood
      cell casts. Azotemia, when present, subsided in 9.4 days. The average diastolic
      pressure was 105 mm. of mercury and the mean fall was 26 mm. in 23.5 days. At six
      months, nine of the 13 patients still being observed continued to show
      proteinuria or microscopic hematuria (seven showed both). A late follow-up of ten
      patients showed one to have significant hypertension and one to have early
      functional impairment and inconstant proteinuria. In these cases the average
      blood pressure was 140/91 mm. as compared with 119/74 mm. at the time of
      discharge. Sporadic glomerulonephritis in adults presents essentially the same
      pattern as it does in children. Urinary abnormalities may persist for months or
      even years, and neither the present series nor those reported by others clearly
      reveal the ultimate prognosis.

PMID- 18732528
TI  - Another Annual Meeting.

PMID- 18732529
TI  - The Scientific Board.

PMID- 18732530
TI  - Samuel R. Sherman, M.D., C.M.A. President-Elect.

PMID- 18732531
TI  - In Memoriam.

PMID- 18732532
TI  - PUBLIC HEALTH REPORT.

PMID- 18732533
TI  - "You Gotta Have Heart,".

PMID- 18732534
TI  - Hysterectomy.

PMID- 18732535
TI  - Retroperitoneal Free Air.

PMID- 18732536
TI  - Time for Unification.

PMID- 18732537
TI  - In Memoriam.

PMID- 18732538
TI  - PUBLIC HEALTH REPORT.

PMID- 18732540
TI  - WOMAN'S AUXILIARY.

PMID- 18732539
TI  - Hospital Bills-What Portion Is Paid by Insurance?-Report of Bureau of Research
      and Planning.
AB  - A two-year survey result-ending some 18 months ago and just released-reveals that
      68 per cent of all short-stay hospital discharges had hospitalization coverage.
      Insurance paid three-fourths or more of the bill for over 75 per cent of those
      covered.One-half of the discharges in the 65+ age group were covered. Almost 60
      per cent of this group had three-fourths or more of the hospital bill paid by
      voluntary health insurance. The 65+ group with family income under $4,000 had
      better protection than age groups under age 45. The highest per cent of coverage
      was in the 45 to 64 age group where over 75 per cent of the discharges had
      coverage, with insurance paying more than three-fourths of the bill. This is the
      group which is likely to retain coverage upon retirement.

PMID- 18732541
TI  - Proposed Constitutional Amendments.

PMID- 18732542
TI  - Proposed Bylaw Amendments.

PMID- 18732543
TI  - California Medical Association 1963 Annual Meeting Announcement.

PMID- 18732544
TI  - The Industrial "Blank Check,".

PMID- 18732545
TI  - PUBLIC HEALTH REPORT.

PMID- 18732546
TI  - California Physicians' Service.

PMID- 18732547
TI  - In Memoriam.

PMID- 18732548
TI  - WOMAN'S AUXILIARY: MEMBERSHIP AND ORGANIZATION.

PMID- 18732550
TI  - WHAT SCOPE HEALTH INSURANCE?

PMID- 18732551
TI  - The Next Step.

PMID- 18732549
TI  - The Inability of the Consumer Price Index to Measure "Cost of Quality" of Medical
      Care, Report of the Bureau of Research and Planning.
AB  - The Consumer Price Index (CPI) of the Bureau of Labor Statistics is an index
      which measures the price changes of 300 goods and services. Among these 300 items
      are several which reflect price changes for selected health care and medical care
      services. These comprise the medical care index and physician fee index,
      depending on what services are being measured. THE PHYSICIAN FEE INDEX IS BASED
      UPON CHARGES FOR FIVE PROCEDURES RENDERED BY PHYSICIANS: Appendectomy,
      tonsillectomy, obstetrical delivery, home visits and office visits. Although the
      CPI takes into account quality changes in the prices for various goods, it is
      unable to do so for services, particularly physicians' services. The difficulty
      in measuring the "cost" of quality of medical care overstates price increases in
      the physician fee and medical care indexes.

PMID- 18732553
TI  - "Yes" on 22.

PMID- 18732552
TI  - Transactions of the House of Delegates, San Francisco, April 14 to 18, 1962.

PMID- 18732554
TI  - Welcome Forty First.

PMID- 18732555
TI  - In Memoriam.

PMID- 18732556
TI  - Acute Radiation Exposure.

PMID- 18732557
TI  - PUBLIC HEALTH REPORT.

PMID- 18732558
TI  - Type of Practice of Physicians in California, Report of the Bureau of Research
      and Planning.
AB  - The total number of non-federal physicians in California rose from 23,065 in mid
      1959 to 26,271 in January, 1962, an 11.3 per cent increase. The proportion of
      physicians in private active practice remained almost constant during this
      period.A significant rise, both in number and proportionally, took place in the
      full-time specialty category, offset by losses in the general practice-part-time
      specialty group. While specialists increased by over 30 per cent, general
      practitioners, who made up 31.7 per cent of all non-federal physicians in 1959,
      were only 24.7 per cent of the total in early 1962.

PMID- 18732559
TI  - WOMAN'S AUXILIARY: THE IMPORTANCE OF AUXILIARY MEMBERSHIP.

PMID- 18732560
TI  - DRUG THERAPY OF HYPERTENSION.
AB  - Drug therapy can lower the blood pressure levels of most hypertensive patients.
      The agents now in use are usually better tolerated and more effective than many
      of those available a few years ago. It seems probable that there is a close
      relationship between the elevated blood pressure and the increased mortality rate
      of hypertensive persons and that a significant lowering of this pressure would
      result in a decrease in mortality. In a pertinent study, the average pre
      treatment blood pressure of a group of 76 patients with moderate to severe
      hypertension was 198/119 mm. of mercury in the prone position and 192/118 in the
      standing position. The patients were treated for a two-year period and with
      treatment their average pressure over a nine-month period was 164/99 mm. prone
      and 142/94 mm. standing. Many drugs used for the treatment of high blood pressure
      have more effect on the lowering of this pressure when the patient is in the
      standing position. For this reason, the blood pressure, while the patient is
      standing, should be used as the guide for dosage of these drugs.

PMID- 18732562
TI  - Medical Assistance to the Aged.

PMID- 18732561
TI  - ANXIETY AND WORRY AS ASPECTS OF NORMAL BEHAVIOR.
AB  - Anxiety and worry are not necessarily psychopathological reactions. Anxiety is a
      basic physiological and affective response to the perception of danger. Worry is
      an effort to deal with the perceived threat at an intellectual level. Realistic
      anxiety and worry, based on objective and realistic dangers, should be
      distinguished from neurotic anxieties and worries. Within certain limits
      realistic anxiety and worry are useful adaptive mechanisms which enable a person
      to cope more effectively with anticipated dangers. Excessive anxiety and worry,
      however, or the absence of these reactions in circumstances where they would be
      appropriate, both tend to lead to maladaptive responses. These considerations
      have certain useful implications in medicine, notably in the preparation of
      patients for surgical operation.

PMID- 18732563
TI  - Medical Education Loans.

PMID- 18732564
TI  - Parathion Poisoning-A New Antidote!

PMID- 18732566
TI  - In Memoriam.

PMID- 18732565
TI  - PUBLIC HEALTH REPORT.

PMID- 18732567
TI  - WOMAN'S AUXILIARY: COMMUNITY SERVICE.

PMID- 18732568
TI  - The Financing and Provision of Medical Care in California, Report of the Bureau
      of Research and Planning.

PMID- 18732569
TI  - THE HAZARDS OF RADIATION.

PMID- 18732570
TI  - HAY FEVER-A Comparative Clinical Evaluation of Treatment with Aqueous Pollen
      Extracts, Alum-Precipitated Pyridine Pollen Extracts and Aqueous Pollen in Oil
      Emulsions.
AB  - Three different types of pollen extracts are currently being used in the
      prophylactic treatment of hay fever. A comparative clinical study of their
      efficacy reveals that all are about equally efficacious. The alum-precipitated
      pyridine pollen extracts may be slightly better. Since only 14 to 16 injections
      are required for prophylactic treatment, they may well replace the older aqueous
      pollen extracts, 20 to 35 injections of which are usually necessary to provide
      relief. The aqueous pollen in oil repository method of treatment needs only one
      to four injections for comparable results, but this so-called "one-shot"
      treatment can only be administered by one who is trained in emulsion therapy and
      has come to know by experience the proper maximum dose.

PMID- 18732571
TI  - BRONCHOGRAPHIC CONTRAST MEDIUMS.
AB  - In a study of 102 bronchograms for purposes of comparing the contrast medium
      Visciodol(R) (a mixture of iodized peanut oil and powdered sulfanilamide) with
      Iodochlorol(R) (an iodized poppyseed oil), it was observed that Visciodol is more
      readily administered, produces better bronchograms with less alveolar filling and
      clears from the lungs far more rapidly and completely than does Iodochlorol.
      Certain even newer highly promising agents are available but specific results
      with them are not included with this report. Bronchography is a diagnostic
      procedure that is contraindicated when the information to be gained does not
      exceed the probable risk.

PMID- 18732572
TI  - Communications.

PMID- 18732573
TI  - In Memoriam.

PMID- 18732575
TI  - PUBLIC HEALTH REPORT.

PMID- 18732574
TI  - "Second Aid,".

PMID- 18732576
TI  - WOMAN'S AUXILIARY: THE AUXILIARY AND POLITICS.

PMID- 18732577
TI  - LETTERS TO THE EDITOR.

PMID- 18732578
TI  - Characteristics of Physicians in California, Report of Bureau of Research and
      Planning.

PMID- 18732579
TI  - Physicians' Use of Relative Value Studies, Report of Bureau of Research and
      Planning.
AB  - Data tabulated from the Study of the Characteristics of Physicians in California,
      conducted by the C.M.A. Bureau of Research and Planning, show that over 70 per
      cent of all physicians in active private practice utilize the Relative Value
      Studies, with over 41 per cent stating that they use it "all or most of the
      time." Use figures range from almost 78 per cent of physicians who participate in
      some form of prepayment program to under 53 per cent of physicians who do not
      participate in any such program.Eighty per cent of all physicians in private
      practice who use the RVS expressed general satisfaction, with 11.8 per cent
      dissatisfied and 8.2 per cent stating no opinion as to their satisfaction. Of the
      80 per cent who expressed satisfaction, two out of three use the RVS all or most
      of the time.

PMID- 18732580
TI  - Objectives and Program of the A.M.A. Committee on Nursing.
AB  - The continued achievement of high standards of patient care in the preventive,
      curative, and restorative aspects of illness depends upon a harmonious,
      collaborative relationship between medicine and nursing. In an effort to protect
      and foster an enduring alliance of understanding and cooperation between these 2
      major health professions, the Committee on Nursing has instituted a continuing
      program of liaison, communication, education, and research. The Committee has
      authorized publication of the following report on its objectives and program.

PMID- 18732581
TI  - SINGLE-DOSE TREATMENT OF ENTEROBIASIS-Use of a New Piperazine-Senna Preparation.
AB  - A preparation combining piperazine and senna was clinically tested among 31
      families in which at least one member was found to be positive for enterobiasis
      by the customary cellophane-tape anal smear technique. The diagnostic smears were
      positive for 58 of those tested. Following a single dose of piperazine-senna
      mixture, all patients were cleared of the infestation as determined by the
      customary criteria for cure. In six patients in two families, reinfestation
      occurred in two to three months after the first administration. All were again
      cleared with one dose of the mixture. Side effects were insignificant and
      transient. One 4-year-old child vomited, but an hour later ingested a second dose
      without incident. The preparation was palatable and easily administered.

PMID- 18732582
TI  - Papillary Carcinoma of the Renal Pelvis Following Cystectomy and Bricker
      Procedure for Carcinoma of the Bladder.

PMID- 18732584
TI  - Principles of a Sound Program for Medical Care.

PMID- 18732583
TI  - The Keogh Bill.

PMID- 18732585
TI  - Proposed Amendments to the Constitution and Bylaws.

PMID- 18732586
TI  - Pre-Placement Physical Examinations-Asset or Liability?

PMID- 18732587
TI  - In Memoriam.

PMID- 18732588
TI  - Health Insurance for Senior Citizens, Report of Bureau of Research and Planning.
AB  - A recent report by the Health Insurance Institute indicates that, as of October
      1962, 55 per cent of the total non-institutionalized aged population in the
      United States were enrolled in some form of voluntary health insurance. More than
      200 organizations, nationally, provide coverage for the more than nine million
      senior citizens.A recent survey by the California Medical Association's Bureau of
      Research and Planning reveals that 70 insurance and prepayment organizations
      offer 140 programs for such coverage on a guaranteed renewable basis in the State
      of California. The Bureau's survey did not attempt to secure the number of aged
      enrolled, since its objective was to determine the nature and the number of the
      programs available. The accompanying text describes the variety of plans
      available to the aged in California on a guaranteed renewable basis.

PMID- 18732589
TI  - LIQUID NITROGEN THERAPY OF WARTS-An Evaluation.
AB  - The use of liquid nitrogen for the removal of warts has advantages over
      electrocautery in certain circumstances. Although the incidence of recurrences
      after liquid nitrogen is higher than after cautery, it causes considerably less
      scarring. It is most useful in dealing with peri-ungual and multiple warts. The
      technique is simple and a supply of liquid nitrogen can be kept on hand in the
      office at relatively low cost.

PMID- 18732591
TI  - Unification Complete.

PMID- 18732590
TI  - RHEUMATOID ARTHRITIS-Operations on the Hand for Improvement of Function.
AB  - Once the deformities of rheumatoid arthritis of the hand begin to develop,
      conservative management will not prevent their further development. The ulnar
      drift of the fingers can be improved considerably by a surgical operation,
      especially if performed early. Experience has shown that an operation performed
      during the active stage of the disease does not cause exacerbation of symptoms.
      The results of operations have been encouraging with regard to return of
      function, decrease in pain and improved appearance of the hand.

PMID- 18732592
TI  - A.M.A. Meets in Los Angeles.

PMID- 18732593
TI  - Proposed Amendments to the Constitution and Bylaws.

PMID- 18732594
TI  - Closed Chest Cardiac Resuscitation and the Industrial Nurse.

PMID- 18732595
TI  - In Memoriam.

PMID- 18732596
TI  - PUBLIC HEALTH REPORT.

PMID- 18732597
TI  - Arational Behavior and Medical Care, Report of Bureau of Research and Planning.
AB  - Testing the hypothesis that arationality on the part of a patient in the
      treatment of an illness is in direct relation to perceived chance or danger
      inherent in that illness and is in inverse relation to medical knowledge about
      that illness, the authors of an unpublished doctoral dissertation conclude that
      "those who are scientifically more knowledgeable" in the area of medical practice
      are "also more rational." Arational behavior is categorized as 1) the type that
      involves the use of, or belief in the efficacy of accepted religious practices
      for the treatment of illness, 2) the use of some religious charms and trinkets,
      and 3) the use of ineffective or harmful health foods, herbs, and various
      compounds. The authors conclude that an increase in technological discoveries
      will result in a trend toward greater rationality and more rational behavior in
      seeking treatment for illness.

PMID- 18732598
TI  - In Memoriam.

PMID- 18732599
TI  - Misnomers, Missed Diagnosis, Ineffective Therapy and Legal Cripples.

PMID- 18732600
TI  - PUBLIC HEALTH REPORT.

PMID- 18732602
TI  - Rural Health.

PMID- 18732601
TI  - Income, Health Expenses, Medical Debts, and Assets of Older Persons, Report of
      Bureau of Research and Planning.
AB  - Recent publicity in the A.M.A. News and in the New York Times regarding income,
      debts, and medical care expenditures of older persons referred to the 1961 Survey
      of Consumer Finances by the Survey Research Center of the University of Michigan,
      and to findings of the 1960 Census. The purpose of this Socio-Economic Report is
      to provide some of the details of the Michigan survey, to introduce data recently
      published by the Department of H.E.W., and to present certain income estimates by
      the Bureau of Research and Planning. The terms "spending unit" and "family unit"
      can be confusing unless defined.A "spending unit" consists of all related persons
      living together who pool their income. An individual living alone may also be a
      spending unit.A "family unit" consists of two or more related persons living in
      the same dwelling unit.

PMID- 18732603
TI  - Decrease in Serum Cholesterol With Surgical Stress.

PMID- 18732605
TI  - Medical Student Loans.

PMID- 18732604
TI  - PRESENT STATUS OF DERMABRASION.
AB  - The use of dermabrasion for cosmetic purposes is becoming less popular due to
      limitations inherent in the method despite the fact that it is still the best
      method available for the minimizing of acne scarring. Planing for precancerous
      skin is increasing in demand because of definite benefits to be gained from its
      use. While the method has not attained universal acceptance for the latter
      purpose, 80 per cent of dermatologists who have tried this approach, and who
      answered a questionnaire, rate the benefits obtained as excellent or good. Only
      3.5 per cent considered the results as poor. In a five-year period between two
      questionnaires, there was in general a trend away from enthusiasm for this
      modality, but esteem for it as a way of dealing with precancerous skin held up
      better than opinion of its use for cosmetic purposes.

PMID- 18732606
TI  - MYCOSIS FUNGOIDES-Local Injection of Triamcinolone.
AB  - Three patients with mycosis fungoides in the thickened plaque and early tumor
      stages of the disease were treated with intralesional injections of triamcinolone
      solution. Both triamcinolone diacetate and acetonide in concentrations of 0.75
      per cent or higher were effective in reducing the tumors and symptomatically
      controlling the pruritus. Other parts of the same lesions treated with other
      substances or not treated remained unchanged.

PMID- 18732608
TI  - The Scientific Board.

PMID- 18732607
TI  - Keogh Preparations.

PMID- 18732609
TI  - In Memoriam.

PMID- 18732610
TI  - PUBLIC HEALTH REPORT.

PMID- 18732611
TI  - WOMAN'S AUXILIARY: Health Careers.

PMID- 18732612
TI  - Socio-Economics of Medical Care, Report of Bureau of Research and Planning.
AB  - Interest in the area of medical socio-economics has largely come about due to the
      proliferation of social welfare programs and advances in the distribution of
      health services in the private sector of the economy. The increasing role of our
      government has also been a stimulus. With the advent of new techniques for the
      financing of care, a large volume of institutional literature has appeared
      delving into issues which range from the role of the medical profession in the
      evaluation of quality of medical care to the measurement of demand for and
      prepayment of numerous types of health care services. Since the area of medical
      socio-economics is not considered "pure" enough to be categorized as a
      discipline, the range of periodicals, government and non-government publications
      and books, in which data are found, is vast. This report will briefly describe
      some of the more important sources of data in the area of medical socio
      economics. Major emphasis is given to the literature which provides current
      statistical data on the operational aspects of public and private programs
      providing health care services, and ancillary activities which affect the market
      for health care activities. Leading publications of governmental and other
      community agencies are cited to illustrate the range of materials available to
      the public and to the medical profession.

PMID- 18732614
TI  - Antivivisection.

PMID- 18732613
TI  - Cancer-Report on Study of Service Needs of Some Cancer Patients in California.

PMID- 18732615
TI  - Tax-Favored Retirement Funds for Self-Employed.

PMID- 18732617
TI  - Scientific Medical Information.

PMID- 18732616
TI  - LEUKEMIA AFTER RADIOIODINE THERAPY FOR HYPERTHYROIDISM.
AB  - In a group of 650 patients with hyperthyroidism treated with radioiodine between
      1945 and 1961, two cases of leukemia occurred. In one patient the diagnosis of
      chronic lymphatic leukemia was made three years after the I(131) therapy. Acute
      or subacute myelomonocytic leukemia developed in the other patient after an
      interval of 14 years. However, no conclusions can be drawn regarding a possible
      causal relationship between such therapy and the subsequent occurrence of
      leukemia. With passage of time, an ever increasing number of cases of leukemia
      can be expected in such patients on the basis of natural occurrence alone.

PMID- 18732619
TI  - In Memoriam.

PMID- 18732618
TI  - Occupational Disease in California.

PMID- 18732620
TI  - WOMAN'S AUXILIARY: WOMAN'S AUXILIARY TO THE CALIFORNIA MEDICAL ASSOCIATION.

PMID- 18732621
TI  - Participation of California Physicians in Emergency Medical Care Panels, Report
      of Bureau of Research and Planning.
AB  - Over 40 per cent of all California physicians belonged to some type of emergency
      medical care panel during 1961. Of these physicians, almost 60 per cent were
      affiliated with hospital panels and 27 per cent with County Society panels. Other
      findings indicate the following facts about physician participation in emergency
      care panels:...84 per cent of physicians who participate do so on a voluntary
      basis, with 16 per cent belonging to panels on a compulsory basis....higher than
      average per cents of physicians belong to such panels in rural
      areas....compulsory membership is more prevalent in hospital panels than in
      County Society panels.

PMID- 18732623
TI  - 1963 Annual Session.

PMID- 18732622
TI  - Massive Fatal Bleeding from Colonic Diverticulitis.

PMID- 18732624
TI  - The Voice of the Physician.

PMID- 18732625
TI  - Peripatetic President.

PMID- 18732627
TI  - Annis Quotes.

PMID- 18732626
TI  - James C. Doyle, M. D. C. M. A. President-Elect.

PMID- 18732628
TI  - Do You Hear Me?

PMID- 18732630
TI  - PUBLIC HEALTH REPORT.

PMID- 18732629
TI  - In Memoriam.

PMID- 18732631
TI  - Control of Cancer Quackery.

PMID- 18732632
TI  - The Voice of the Physician.

PMID- 18732633
TI  - Some Recent Changes in the Composition of Physicians in California.

PMID- 18732635
TI  - A Letter from the Forty First.

PMID- 18732634
TI  - A Program for Private Insurance With Governmental Backing.

PMID- 18732636
TI  - Funds Needed for Services To Patients.

PMID- 18732637
TI  - ROSACEA-LIKE DEMODICIDOSIS.
AB  - Rosacea-like demodicidosis is an entity resembling acne rosacea which is caused
      by infestation with an abnormally large number of the mite Demodex folliculorum,
      usually in association with improper cleansing of the face. This condition
      responds promptly to external treatment consisting of daily cleaning of the face
      with soap and water and the application of a compound sulfur ointment over a
      period of a few weeks. Occasional instances of a mixed-type of rosacea are
      encountered in which internal factors are involved.

PMID- 18732638
TI  - Intracerebral Hemorrhage as a Complication of Carotid Artery Operations-A Report
      of Two Cases.

PMID- 18732639
TI  - Medicine in Society.

PMID- 18732640
TI  - Report of Ad Hoc Committee No. 2.

PMID- 18732641
TI  - 1962 House of Delegates Ad Hoc Committee No. 2 Report.

PMID- 18732643
TI  - Poison.

PMID- 18732642
TI  - Minority Report of Ad Hoc Committee No. 2.

PMID- 18732645
TI  - In Memoriam.

PMID- 18732644
TI  - Lewis A. Alesen, M. D.

PMID- 18732646
TI  - PUBLIC HEALTH REPORT.

PMID- 18732647
TI  - Kerr-Mills Administration in California.

PMID- 18732648
TI  - Voluntary Health Insurance Coverage in California, 1961: A Report of the Bureau
      of Research and Planning, California Medical Association.
AB  - Almost 7 out of every 10 of the estimated population of 16.2 million persons in
      California, were covered under some form of voluntary health insurance at the end
      of 1961. The forms of protection included hospital, surgical, regular medical and
      major medical expense benefits. The per cent of the civilian population of
      California covered for surgical benefits was slightly over 66 per cent, while 56
      per cent were covered for regular medical expense benefits. Comparable
      percentages for the United States are approximately 74 per cent (hospital), 69
      per cent (surgical), and 51 per cent (regular medical). While the percentage of
      the State's population covered for hospital and surgical expenses is below that
      for the United States, it is higher for regular medical expense benefits. The
      rate of increase in coverage for the different forms of health care protection in
      California exceeded the rate of population growth during the one-year period
      ending 1961. The foregoing summary and the information in the accompanying text,
      does not reflect the total number of persons in California who receive or are
      eligible for health care services. A large variety of government financed
      programs on local, state and federal levels either finance or provide such
      services to an estimated 40 to 50 per cent of the California population, which
      does not have voluntary health insurance coverage. No current data are available
      regarding the number of persons who do not desire voluntary health insurance
      coverage for a variety of personal or financial reasons.

PMID- 18732650
TI  - The A.M.A. Congress on Mental Illness and Health.

PMID- 18732649
TI  - Gynecological Cytology-The Use of Fluorescence Technique, Commission on Cancer.

PMID- 18732652
TI  - The A.M.A. Session.

PMID- 18732651
TI  - PSYCHOLOGICAL ASPECTS OF PAIN IN PATIENTS WITH TERMINAL CANCER.
AB  - The dying patient reacts emotionally to the problems encountered in the terminal
      period according to his established pattern of response to stress. The nature of
      this pattern will play a part in his experience of pain. Some of the types of
      reaction include the bizarre misinterpretation of bodily sensation of the
      psychotic, the development of conversion symptoms, the increase in pain through
      muscle tension in the anxious but overcontrolled person, and the stoical
      acceptance by guilt-ridden patients. Physicians are sometimes reluctant to devote
      full attention to the care of the terminally ill for a number of reasons,
      including the attitude that "curing" is the only worthwhile activity of a doctor
      of medicine. Observers have found that the physician's attention to the day to
      day anxieties of the patient in a terminal stage may contribute substantially to
      his comfort.

PMID- 18732653
TI  - Reporting Drug Dangers.

PMID- 18732654
TI  - Dr. Blain's Influence.

PMID- 18732656
TI  - Transactions of the House of Delegates, Los Angeles, March 23-27, 1963.

PMID- 18732655
TI  - PRESIDENT'S PAGE.

PMID- 18732658
TI  - In Memoriam.

PMID- 18732657
TI  - Proposed Constitutional Amendments.

PMID- 18732659
TI  - George G. Reinle, M. D.

PMID- 18732660
TI  - PUBLIC HEALTH REPORT.

PMID- 18732661
TI  - WOMAN'S AUXILIARY: PROGRAMS OF THE WOMAN'S AUXILIARY.

PMID- 18732662
TI  - California Urges Action on Chloramphenicol-Senate Resolution No. 151.

PMID- 18732663
TI  - The Non-Member.

PMID- 18732664
TI  - Obiter Dicta.

PMID- 18732665
TI  - The Revised "Cancer Studies".

PMID- 18732666
TI  - The New Dean.

PMID- 18732667
TI  - Physician Fee Index Survey, Report of the Bureau of Research and Planning.

PMID- 18732668
TI  - A Fifty-Fifty Chance, Committee on Occupational Health.

PMID- 18732669
TI  - In Memoriam.

PMID- 18732670
TI  - PUBLIC HEALTH REPORT.

PMID- 18732671
TI  - WOMAN'S AUXILIARY: LEGISLATION.

PMID- 18732672
TI  - LETTERS TO THE EDITOR.

PMID- 18732673
TI  - In Memoriam.

PMID- 18732674
TI  - What's That Noise?, Committee on Occupational Health.

PMID- 18732675
TI  - PUBLIC HEALTH REPORT.

PMID- 18732676
TI  - WOMAN'S AUXILIARY: COMMUNITY SERVICE.

PMID- 18732677
TI  - Public Provisions of Medical Benefits Regardless of Ability to Pay, Report of the
      Bureau of Research and Planning.

PMID- 18732678
TI  - Locum Tenens.

PMID- 18732679
TI  - Role of the Private Physician in Coordinated Home Care.

PMID- 18732680
TI  - In the Interim.

PMID- 18732681
TI  - In Memoriam.

PMID- 18732682
TI  - Clarification of the Informed Consent Rule.

PMID- 18732683
TI  - Selected Physician Characteristics in California as of April 1963, Report of the
      Bureau of Research and Planning.

PMID- 18732684
TI  - Educational Programs in Nursing and Related Career Opportunities.

PMID- 18732685
TI  - Experience Under the M.A.A. Program in California, 1962, Report of the Bureau of
      Research and Planning.

PMID- 18732687
TI  - Stress and Heart Disease, Report of the Committee on Scientific Information of
      the Scientific Board, California Medical Association.

PMID- 18732686
TI  - Hormonal Therapy of Disseminated Mammary Cancer.

PMID- 18732688
TI  - A C.M.A. Keogh Plan for Retirement Income.

PMID- 18732689
TI  - The Editorial Board.

PMID- 18732691
TI  - Change in Work Injury Report, Committee on Occupational Health.

PMID- 18732690
TI  - Back to Light Work, Committee on Occupational Health.

PMID- 18732692
TI  - In Memoriam.

PMID- 18732693
TI  - PUBLIC HEALTH REPORT.

PMID- 18732694
TI  - WOMAN'S AUXILIARY.

PMID- 18732695
TI  - Health Care-Expenditures in Welfare Programs, Report of the Bureau of Research
      and Planning.

PMID- 18732696
TI  - Federal Medical-Health Care Services-Appropriations for Fiscal Year 1963 (July 1,
      1962 to June 30, 1963), Report of the Bureau of Research and Planning.

PMID- 18732698
TI  - Labels on Prescription Drugs.

PMID- 18732697
TI  - An Outstanding Annual Session Program.

PMID- 18732700
TI  - Handicapped Lungs, Committee on Occupational Health.

PMID- 18732699
TI  - Proposed Amendments to Constitution.

PMID- 18732701
TI  - In Memoriam.

PMID- 18732702
TI  - PUBLIC HEALTH REPORT.

PMID- 18732703
TI  - WOMAN'S AUXILIARY: Physicians' Benevolence.

PMID- 18732704
TI  - Environment Under the Federal Employees Health Benefits Program: A Report of the
      Bureau of Research and Planning, California Medical Association.
AB  - Active and retired federal employees, together with their dependents, represent
      the single largest group of persons enrolled in any voluntary health insurance
      program in the United States. The extent of their coverage and enrollment is of
      particular interest to physicians in California since this state has the largest
      proportion of all federal employees enrolled among all states. Of the almost
      5(3/4) million federal employees and their dependents, enrollment in California
      was almost 609,000 or slightly over 10 per cent of all those covered. Better than
      3 out of 5 individuals covered were enrolled in service type plans both in the
      U.S. and in California. Of all persons enrolled in comprehensive group practice
      and individual practice plans in the U.S., almost one-half were in California
      alone. Almost 4 out of 5 individuals enrolled were in high option plans. "... an
      indication that most employees were satisfied with their initial choice of
      plans."

PMID- 18732705
TI  - PURPOSE OF THE STATE JOURNAL.

PMID- 18732706
TI  - MEMBERSHIP IN STATE SOCIETY.

PMID- 18732707
TI  - DEATHS.

PMID- 18732708
TI  - The Mastoid Operation in Chronic Suppurative Otitis Media.

PMID- 18732709
TI  - TRI-COUNTY SOCIETY.

PMID- 18732710
TI  - Los Angeles Health Officer on Transmissible Diseases.

PMID- 18732711
TI  - IMPORTANCE OF AFFILIATION.

PMID- 18732713
TI  - Constitution and By-laws of Medical Society of State of California.

PMID- 18732712
TI  - San Francisco Vital Statistics.

PMID- 18732714
TI  - CHARACTER OF ADVERTISING.

PMID- 18732715
TI  - LORENZ VISITS SAN FRANCISCO.

PMID- 18732717
TI  - PATHOLOGICAL CONGRESS.

PMID- 18732716
TI  - IMPORTANT ADDITION.

PMID- 18732718
TI  - SAN FRANCISCO AND THE PLAGUE.

PMID- 18732719
TI  - PROTECTION IN ORGANIZATION.

PMID- 18732720
TI  - URGENT NEED OF RESEARCH WORK.

PMID- 18732721
TI  - Notes on Prof. Lorenz' Visit.

PMID- 18732722
TI  - The Aleuts, by a Layman.

PMID- 18732724
TI  - PHARMACEUTICAL STANDARDIZATION.

PMID- 18732723
TI  - Report of a Fatal Case of Gastro-Duodenal Ulcer.

PMID- 18732725
TI  - ORGANIZATION PROGRESSING.

PMID- 18732726
TI  - AN OBVIOUS DUTY BEFORE WEDLOCK.

PMID- 18732727
TI  - AFFILIATION OF THE COUNTY SOCIETIES.

PMID- 18732728
TI  - SCIENTIST TO BE AT THE HELM.

PMID- 18732729
TI  - COMMERCIAL vs PROFESSIONAL.

PMID- 18732730
TI  - ORGANIZATION IN COUNTIES.

PMID- 18732731
TI  - Necessity of Standardizing Materia Medica Products.

PMID- 18732732
TI  - Certified Mineral Waters (Excerpt).

PMID- 18732733
TI  - Report of a Case of Bubonic Plague.

PMID- 18732734
TI  - DEATHS.

PMID- 18732735
TI  - Points in the Management of Cleft Palate Cases.

PMID- 18732736
TI  - Suturing of Muscles and Tendons.

PMID- 18732737
TI  - Discussion on Dr. Crowley's Paper.

PMID- 18732738
TI  - ANTI-TUBERCULOSIS LEAGUE.

PMID- 18732739
TI  - Health of Allied Forces in China.

PMID- 18732740
TI  - San Francisco Vital Statistics.

PMID- 18732741
TI  - COVERT ATTACK ON MEDICAL LAW.

PMID- 18732742
TI  - WORD "PATENT" A MISNOMER.

PMID- 18732743
TI  - STATE SOCIETY APRIL MEETING.

PMID- 18732744
TI  - MEMBERSHIP IN A. M. A. DEFINED.

PMID- 18732746
TI  - PURE FOOD BILL IN CONGRESS.

PMID- 18732745
TI  - PROTECTION FOR PRACTITIONERS.

PMID- 18732747
TI  - PROF. LORENZ AND HIS CLAIM.

PMID- 18732748
TI  - THE JOURNAL ADVERTISERS.

PMID- 18732750
TI  - Correspondence.

PMID- 18732749
TI  - INEXCUSABLE DELINQUENCY.

PMID- 18732752
TI  - Correspondence.

PMID- 18732751
TI  - Post Occipital Lymphadenitis; Southern California and the State Society.

PMID- 18732753
TI  - Correspondence.

PMID- 18732754
TI  - Correspondence.

PMID- 18732755
TI  - Progressive Muscular Atrophy of Spinal Origin.

PMID- 18732756
TI  - DEATHS.

PMID- 18732757
TI  - Medical Legislation in California.

PMID- 18732758
TI  - State Hospital Care and Treatment of the Acute and Convalescing Insane.

PMID- 18732760
TI  - Oophorectomy-Its Effect on the Mind and Nervous System.

PMID- 18732759
TI  - Is Another Chapter in Public Phthisiophobia About to be Written?

PMID- 18732761
TI  - The Prophylaxis of Venereal Disease.

PMID- 18732762
TI  - Pott's Disease.

PMID- 18732763
TI  - CALIFORNIA ACADEMY OF MEDICINE.

PMID- 18732764
TI  - In Pneumonia.

PMID- 18732765
TI  - Spinal Anesthesia with Tropa-Cocaine in Genito-Urinary Surgery.

PMID- 18732766
TI  - Ptomaine Poisoning.

PMID- 18732767
TI  - Hygiene.

PMID- 18732768
TI  - DEATH.

PMID- 18732769
TI  - Miscellany.

PMID- 18732770
TI  - HEALTH BOARD IS VINDICATED.

PMID- 18732771
TI  - USEFULNESS OF COUNTY SOCIETY.

PMID- 18732772
TI  - A QUESTION OF "PURE FOOD.".

PMID- 18732773
TI  - INSPECTION OF MILK.

PMID- 18732774
TI  - NEW YORK'S PHENACETIN.

PMID- 18732775
TI  - LIMITS IN ADVERTISING.

PMID- 18732776
TI  - THE EDDYITE BOOK CONCERN.

PMID- 18732777
TI  - THE INDEX MEDICUS.

PMID- 18732778
TI  - EDDYITE MODESTY.

PMID- 18732779
TI  - Criticisms.

PMID- 18732780
TI  - THE BUBONIC PLAGUE: From Northwest Medicine, Seattle.

PMID- 18732782
TI  - THE MEETING AT SANTA BARBARA.

PMID- 18732781
TI  - THE REGISTER OF PHYSICIANS.

PMID- 18732784
TI  - ANALYSES OF PURE DRUGS.

PMID- 18732783
TI  - THE PUBLIC TO BE PROTECTED.

PMID- 18732785
TI  - RECENT HISTORY AND THE JOURNAL.

PMID- 18732787
TI  - STRENGTH OF ORGANIZATION.

PMID- 18732786
TI  - LACK OF STANDARD.

PMID- 18732789
TI  - PERSONALITIES VS. ORGANIZATION.

PMID- 18732788
TI  - NATIONAL BUREAU AND THE A. M. A.

PMID- 18732791
TI  - NO MEDICAL LEGISLATION.

PMID- 18732790
TI  - REPORTS FROM THE COUNTIES.

PMID- 18732792
TI  - IMPORTANT PROGRAM.

PMID- 18732793
TI  - PROPRIETARY PREPARATIONS.

PMID- 18732794
TI  - National Bureau of Medicines and Foods: For Pure and Honest Drugs, Chemicals and
      Food-Stuffs.

PMID- 18732795
TI  - SAN FRANCISCO COUNTY MEDICAL SOCIETY.

PMID- 18732796
TI  - Final Result of Operation, Lorenz Method, for Congenital Luxation of Hip (with
      radiograph).

PMID- 18732797
TI  - Manifesto on Use of Alcohol.

PMID- 18732798
TI  - VOLUME ENDS WITH THE YEAR.

PMID- 18732799
TI  - HOW TO AVOID IRREGULARITY.

PMID- 18732800
TI  - TO REPRESENT ENTIRE STATE.

PMID- 18732802
TI  - NEW CLINICAL COAST MATERIAL.

PMID- 18732801
TI  - SHOULD JOIN COUNTY BODY.

PMID- 18732804
TI  - IGNORANCE AND PROGRESS.

PMID- 18732803
TI  - RESTRICTIVE LEGISLATION.

PMID- 18732805
TI  - SANTA BARBARA ADDRESSES.

PMID- 18732806
TI  - Veto Message, Governor Utah, Osteopath Bill.

PMID- 18732807
TI  - Monthly Journal vs. Yearly Volume.

PMID- 18732808
TI  - Iodid of Potash Eruptions.

PMID- 18732809
TI  - Correction of An Imperfect Operation.

PMID- 18732811
TI  - JOSEPH R. LAINE.

PMID- 18732810
TI  - Report Memorial Committee.

PMID- 18732813
TI  - JAMES F. McCONE.

PMID- 18732812
TI  - GREGORY J. PHELAN.

PMID- 18732814
TI  - CEPHAS L. BARD.

PMID- 18732815
TI  - ROSS C. KIRKPATRICK.

PMID- 18732817
TI  - GEORGE WALKER WESTLAKE.

PMID- 18732816
TI  - GEORGE A. CUTTER.

PMID- 18732818
TI  - JOSEPH STEELE EASTMAN.

PMID- 18732820
TI  - MATTHEW GARDNER.

PMID- 18732819
TI  - Tropical Diseases in California.

PMID- 18732821
TI  - DEATHS.

PMID- 18732822
TI  - How Far Shall State Restrict Individual Action of the Sick?

PMID- 18732824
TI  - Puerperal Eclampsia.

PMID- 18732823
TI  - Intraabdominal Shortening of the Round Ligaments for Retrodisplaced Uteri.

PMID- 18732825
TI  - THE BOARD OF EXAMINERS.

PMID- 18732827
TI  - "SCIENTIFIC" EDITORIALS.

PMID- 18732826
TI  - MILK SUPPLY SUPERVISION.

PMID- 18732828
TI  - UNIVERSITY EPIDEMICS.

PMID- 18732829
TI  - COMMITTEE ON TUBERCULOSIS.

PMID- 18732830
TI  - THE POWER OF ORGANIZATION.

PMID- 18732831
TI  - REORGANIZATION OF PROFESSION.

PMID- 18732832
TI  - CODE OF ETHICS NOW INOCUOUS.

PMID- 18732833
TI  - TROUBLE FOR DELINQUENTS.

PMID- 18732835
TI  - STATE SOCIETY ANNUAL MEETING.

PMID- 18732834
TI  - REPORTS FROM COUNTY BODIES.

PMID- 18732836
TI  - STATE SOCIETY'S SCIENTIFIC WORK.

PMID- 18732837
TI  - ADVISE REMOVAL OF CHINATOWN.

PMID- 18732838
TI  - THE REPORT OF THE A. M. A. COMMITTEE ON MEDICAL EDUCATION.

PMID- 18732839
TI  - THE CITY AND COUNTY HOSPITAL AND THE TRADES UNIONS.

PMID- 18732840
TI  - RECIPROCITY.

PMID- 18732841
TI  - DEATH.

PMID- 18732842
TI  - REGISTER OF PHYSICIANS.

PMID- 18732843
TI  - Report on Medical Legislation.

PMID- 18732844
TI  - Report of Board of Examiners.

PMID- 18732846
TI  - A Few Remarks on Gastric Surgery.

PMID- 18732845
TI  - Prostatic Obstructions and Their Removal.

PMID- 18732847
TI  - Bone Transplanting and Report of a Case.

PMID- 18732848
TI  - OFFICIAL REGISTER OF PHYSICIANS.

PMID- 18732849
TI  - PROGENY INSURANCE.

PMID- 18732851
TI  - PHYSICIANS' MUTUAL AID ASSOCIATION.

PMID- 18732850
TI  - ORGANIZATION GROWING APACE.

PMID- 18732852
TI  - WHY PLACE WAS SELECTED.

PMID- 18732853
TI  - CONTRACT DOCTORS.

PMID- 18732855
TI  - FOOD OR POISON?

PMID- 18732854
TI  - THE JOURNAL IS YOURS.

PMID- 18732856
TI  - "JOURNAL" AND MEDICAL NEWS.

PMID- 18732857
TI  - COMMITTEE ON TUBERCULOSIS.

PMID- 18732859
TI  - MEDICAL ETHICS.

PMID- 18732858
TI  - TO ABOLISH SUB-STREET MANUFACTORIES.

PMID- 18732860
TI  - DEATH.

PMID- 18732861
TI  - National Bureau of Medicines and Foods, Statement of Plan.

PMID- 18732862
TI  - Report of Committee on Necrology, 1902.

PMID- 18732863
TI  - ADDITIONS TO MATERIA MEDICA.

PMID- 18732864
TI  - ATTACK ON MEDICAL LAW.

PMID- 18732866
TI  - PHARMACY AND MEDICINE.

PMID- 18732865
TI  - PHYSICIANS: ARE THEY IDIOTS?

PMID- 18732867
TI  - COCAIN HABIT.

PMID- 18732868
TI  - THERAPEUTIC VALUE OF X-RAYS.

PMID- 18732869
TI  - DIRECTORY OF PHYSICIANS.

PMID- 18732870
TI  - THE RED CROSS MUDDLE.

PMID- 18732871
TI  - A CHECK TO LEGALIZED BLACKMAIL.

PMID- 18732872
TI  - PHYSICIANS' CARD FILE.

PMID- 18732873
TI  - COUNTY HOSPITAL NEEDS.

PMID- 18732874
TI  - An Unusual Infection Causing Acute Suppurative Appendicitis.

PMID- 18732875
TI  - Ununited Fractures of Lower Extremity.

PMID- 18732877
TI  - Diploma vs. Certificate.

PMID- 18732876
TI  - Study of the Health of University Girls.

PMID- 18732878
TI  - The Cure of Cross Eyes.

PMID- 18732879
TI  - Principles of Medical Ethics of the A. M. A.

PMID- 18732880
TI  - Appendicitis; with Tabulated Report.

PMID- 18732882
TI  - INITIAL PUBLICATION.

PMID- 18732881
TI  - Scamp and Criminal.

PMID- 18732884
TI  - WORK FOR EVERY MEMBER.

PMID- 18732883
TI  - SCIENTIFIC EDITORIALS.

PMID- 18732885
TI  - MEDICAL SOCIETIES AND PUBLIC PRESS.

PMID- 18732886
TI  - RELIEF IN SIGHT.

PMID- 18732887
TI  - THE CARELESS PHARMACIST.

PMID- 18732888
TI  - THE CURIOUS MANUFACTURER.

PMID- 18732889
TI  - FROUDE-CARLYLE.

PMID- 18732890
TI  - IGNORANCE OF MEDICINE.

PMID- 18732891
TI  - SECRETARIES SHOULD ASSIST.

PMID- 18732892
TI  - A NEW DEPARTMENT.

PMID- 18732893
TI  - TUBERCULOSIS COMMITTEE.

PMID- 18732894
TI  - FINAL JUDGES OF SUCCESS.

PMID- 18732895
TI  - SANTA CLARA RESOLUTIONS.

PMID- 18732896
TI  - THE PUBLICATION COMMITTEE.

PMID- 18732897
TI  - Correction of Deformities.

PMID- 18732898
TI  - Climate of Santa Barbara and Foothill Region.

PMID- 18732900
TI  - Some Further Remarks on Dr. Sherman's Paper Published in August Journal.

PMID- 18732899
TI  - Headache as a Symptom.

PMID- 18732901
TI  - Deaths.

PMID- 18732902
TI  - Materia Medica and Therapeutics.

PMID- 18732905
TI  - SURGICAL ENGLISH.

PMID- 18732904
TI  - ANOTHER SPASM.

PMID- 18732907
TI  - TYPHOID PROPHYLAXIS.

PMID- 18732906
TI  - MISSING NUMBERS.

PMID- 18732908
TI  - INITIAL PUBLICATION.

PMID- 18732909
TI  - TO THE SECRETARIES OF COUNTY SOCIETIES.

PMID- 18732910
TI  - COUNTY SOCIETY TRANSACTIONS.

PMID- 18732912
TI  - PHYSICIANS' DIRECTORY.

PMID- 18732911
TI  - DELINQUENT MEMBERS AND THE JOURNAL.

PMID- 18732913
TI  - MEETING OF HEALTH OFFICERS.

PMID- 18732914
TI  - HIGHER STANDARDS.

PMID- 18732915
TI  - THE CITY AND COUNTY HOSPITAL.

PMID- 18732916
TI  - THIS IS YOUR JOURNAL.

PMID- 18732917
TI  - Initial Publication.

PMID- 18732918
TI  - Further Discussion on Dr. Sherman's Paper Published in August Journal.

PMID- 18732919
TI  - County Society Reports.

PMID- 18732921
TI  - Lupus Erythematosus.

PMID- 18732920
TI  - Excellent Suggestion.

PMID- 18732923
TI  - San Francisco Quarantine Station (Illustrated).

PMID- 18732922
TI  - Deaths.

PMID- 18732924
TI  - A Few Illustrative Cases of Diphtheria.

PMID- 18732926
TI  - Reports of Medical Societies.

PMID- 18732925
TI  - Abdominal Drainage.

PMID- 18732927
TI  - Materia Medica and Therapeutics.

PMID- 18732928
TI  - ILLEGAL PRACTITIONERS.

PMID- 18732929
TI  - THE OREGON STATE SOCIETY.

PMID- 18732930
TI  - HOW MEMBERS MAY ASSIST.

PMID- 18732931
TI  - COMMITTEES ON ADMISSION.

PMID- 18732932
TI  - ORGANIZATION AND THE QUACK.

PMID- 18732934
TI  - TRUTH.

PMID- 18732933
TI  - OFFENSIVE ADVERTISING.

PMID- 18732936
TI  - QUESTIONABLE ENDORSEMENTS.

PMID- 18732935
TI  - THE PROFESSION IN NEW YORK.

PMID- 18732937
TI  - THE CITY AND COUNTY HOSPITAL.

PMID- 18732938
TI  - Tuberculous Infection.

PMID- 18732939
TI  - Correction of Refractive Errors.

PMID- 18732940
TI  - Nature and Treatment of Obesity.

PMID- 18732941
TI  - The Common Rat Best Methods for Destruction.

PMID- 18732942
TI  - Practical Value of State Medical Law.

PMID- 18732944
TI  - Improper Advertising Methods.

PMID- 18732943
TI  - Nihilism in Therapeutics.

PMID- 18732946
TI  - Congress of Ophthalmology.

PMID- 18732945
TI  - Deaths.

PMID- 18732947
TI  - Unauthorized Use of Reprints.

PMID- 18732948
TI  - NEW PHYSIOLOGICAL LABORATORY OF THE UNIVERSITY.

PMID- 18732949
TI  - Materia Medica and Therapeutics.

PMID- 18732951
TI  - Goods Subject to Test.

PMID- 18732950
TI  - Plaster of Paris in Asafoetida.

PMID- 18732953
TI  - NOTICE! REGISTER.

PMID- 18732952
TI  - SUITS AGAINST THE EXAMINERS.

PMID- 18732954
TI  - RATS.

PMID- 18732955
TI  - BOUNTY ON RATS.

PMID- 18732957
TI  - TABLE OF SYNONYMS.

PMID- 18732956
TI  - THE TOY PISTOL.

PMID- 18732959
TI  - THE NEW CONSTITUTION AND BY-LAWS.

PMID- 18732958
TI  - DR. GOULD CRITICIZED.

PMID- 18732960
TI  - EDDYITE THIRST.

PMID- 18732961
TI  - SCHOOL CHILDREN'S EYES.

PMID- 18732962
TI  - A TITLE OF HONOR.

PMID- 18732963
TI  - HOMEOPATHIC EXAMINATIONS.

PMID- 18732964
TI  - Decapsulation of the Kidney for Chronic Bright's Disease.

PMID- 18732965
TI  - Report of Six Cases of Achlorhydria.

PMID- 18732966
TI  - Puerperal Septicemia.

PMID- 18732967
TI  - Tuberculosis in Fowls.

PMID- 18732968
TI  - The Ductless Glands.

PMID- 18732969
TI  - The Prevention of Perineal Lacerations.

PMID- 18732970
TI  - Infectious Pulmonary Edema.

PMID- 18732971
TI  - The Eyes of School Children.

PMID- 18732972
TI  - DEATHS.

PMID- 18732973
TI  - Materia Medica and Therapeutics.

PMID- 18732974
TI  - Proposed New Constitution and By-Laws, State Society (First Instalment).

PMID- 18732975
TI  - PITHY PAPERS.

PMID- 18732976
TI  - SUITS AGAINST THE EXAMINERS.

PMID- 18732977
TI  - A NEW YEAR.

PMID- 18732978
TI  - What is Conservatism in Mastoiditis.

PMID- 18732980
TI  - Deaths: William M. Warren.

PMID- 18732979
TI  - National Bureau of Medicines and Foods.

PMID- 18732982
TI  - A VITAL QUESTION.

PMID- 18732981
TI  - Rupture of the Uterus.

PMID- 18732984
TI  - CONSTITUTION AND BY-LAWS.

PMID- 18732983
TI  - NEW LAWS OR OLD?

PMID- 18732985
TI  - ETIOLOGY OF YELLOW FEVER.

PMID- 18732987
TI  - Eyes of School Children.

PMID- 18732986
TI  - Communication.

PMID- 18732988
TI  - Proposed New Constitution and By-laws, State Society, (Second Installment).

PMID- 18732989
TI  - Materia Medica and Therapeutics.

PMID- 18732990
TI  - Case of Mastoiditis with Mental Disturbance.

PMID- 18732991
TI  - EXAMINATIONS FOR LICENSE.

PMID- 18732992
TI  - THE BUSINESS OFFICE.

PMID- 18732993
TI  - CITY AND COUNTY HOSPITAL SITE.

PMID- 18732994
TI  - Cases of Tuberculosis of Genito-Urinary Tract.

PMID- 18732995
TI  - Peritoneal Adhesions: Their Symptomatology, Pathology and Prevention.

PMID- 18732996
TI  - RIGHT OR DOLLARS?

PMID- 18732997
TI  - ETHICS AND ADVERTISING.

PMID- 18732998
TI  - PRINCIPLES OF ETHICS.

PMID- 18732999
TI  - A SECRET MEDICINE.

PMID- 18733000
TI  - WHAT CAN BE DONE?

PMID- 18733002
TI  - ENFORCEMENT OF THE LAW.

PMID- 18733001
TI  - UTTER RUIN?

PMID- 18733003
TI  - INTERNIST; A NEW ONE.

PMID- 18733004
TI  - SAN FRANCISCO BOARD OF HEALTH.

PMID- 18733005
TI  - ECONOMY AND EFFICIENCY.

PMID- 18733006
TI  - EMBEZZLED FUNDS.

PMID- 18733007
TI  - Two Views of Advertising.

PMID- 18733008
TI  - Professional Ethics.

PMID- 18733009
TI  - Antitoxine Trust.

PMID- 18733011
TI  - Peritoneal Adhesions: Their Symptomatology, Pathology and Prevention.

PMID- 18733010
TI  - Traumatic Neuroses.

PMID- 18733012
TI  - Cases of Tuberculosis of Genito-Urinary Tract.

PMID- 18733013
TI  - Occipito-Posterior Positions.

PMID- 18733014
TI  - Was it a Case of Meningeal Hemorrhage, Hysteria, or Malingering?

PMID- 18733015
TI  - Grawitz Tumor of Kidney.

PMID- 18733016
TI  - Necessity for Systematic Examination of School Children's Eyes, etc.

PMID- 18733017
TI  - AN UNFORTUNATE ERROR CORRECTED.

PMID- 18733018
TI  - Vasectomy: An Argument for its Therapeutic Use in Certain Mental Diseases and as
      a Means of Diminishing Crime and the Number of Criminals.

PMID- 18733019
TI  - Proposed New Constitution and By-laws, State Society (concluded).

PMID- 18733020
TI  - Materia Medica and Therapeutics.

PMID- 18733021
TI  - THANKS FOR RESOLUTIONS.

PMID- 18733022
TI  - EYES, EARS AND NOSES.

PMID- 18733023
TI  - ABOUT PAPERS.

PMID- 18733024
TI  - EFFECTS OF FORMALDEHYDE.

PMID- 18733025
TI  - OUR HEARTY INVITATION.

PMID- 18733026
TI  - INSURANCE EXAMINERS.

PMID- 18733027
TI  - SYPHILIS IN ANTHROPOIDS.

PMID- 18733028
TI  - COLORADO STATE SOCIETY JOURNAL.

PMID- 18733029
TI  - THE UNITED RAILROADS OF SAN FRANCISCO.

PMID- 18733030
TI  - OUR APOLOGY.

PMID- 18733031
TI  - State Board of Health.

PMID- 18733033
TI  - Commercial Opinion.

PMID- 18733032
TI  - FUN WITH THE FOREIGNERS.

PMID- 18733034
TI  - A LETTER.

PMID- 18733035
TI  - AN ILLEGAL PRACTITIONER GONE.

PMID- 18733036
TI  - A Visit to Naha Hospital: Loo Choo Islands.

PMID- 18733037
TI  - Necessity for Systematic Examination of School Children's Eyes, etc.

PMID- 18733038
TI  - Grawitz Tumor of Kidney.

PMID- 18733039
TI  - Undigested Thoughts and Comments.

PMID- 18733041
TI  - Observations on the Prostate Gland in Its Relation to Gonorrhea.

PMID- 18733040
TI  - Case of Chronic Suppurative Disease of Both Frontal Sinuses, etc.

PMID- 18733043
TI  - Gastric Ulcer.

PMID- 18733042
TI  - Contracture of the Vesical Neck.

PMID- 18733044
TI  - Laparotomy-Report of An Operation.

PMID- 18733046
TI  - ATTEND THE MEETING.

PMID- 18733045
TI  - The President, Dr. Ellis.

PMID- 18733047
TI  - ILLEGAL PRACTITIONERS.

PMID- 18733048
TI  - HEALTH OFFICERS.

PMID- 18733050
TI  - THE OTHER EXCEPTION.

PMID- 18733049
TI  - HELP OR HINDRANCE.

PMID- 18733051
TI  - ENFORCE THE LAW.

PMID- 18733052
TI  - SOCIETY JOURNALS.

PMID- 18733053
TI  - TO INVITE THE A.M.A.

PMID- 18733054
TI  - LEGALIZED BLACKMAIL.

PMID- 18733056
TI  - ANOTHER OPINION ON ADVERTISING.

PMID- 18733055
TI  - PURE MILK.

PMID- 18733057
TI  - UNJUST ATTACK.

PMID- 18733058
TI  - Organization and Journal.

PMID- 18733059
TI  - Spitting on Transfers.

PMID- 18733061
TI  - Medical Legislation Committee.

PMID- 18733060
TI  - CORRECTION IN PRELIMINARY PROGRAM.

PMID- 18733062
TI  - Alameda County Annual Dinner.

PMID- 18733063
TI  - Epidemic of Smallpox.

PMID- 18733064
TI  - The Rat and Its Parasites.

PMID- 18733065
TI  - What Causes Appendicitis?

PMID- 18733066
TI  - Legal Definition of Practice of Medicine.

PMID- 18733068
TI  - Neuralgia: Clinical Features.

PMID- 18733067
TI  - Treatment of Primary Glaucoma.

PMID- 18733069
TI  - Asepsis, Especially in Practice of Obstetrics.

PMID- 18733070
TI  - Prosecutions by Board of Medical Examiners.

PMID- 18733071
TI  - DIED.

PMID- 18733072
TI  - Bill to Regulate "Patent Medicines".

PMID- 18733073
TI  - Editorial Pages and Ads.

PMID- 18733074
TI  - Surgical English.

PMID- 18733075
TI  - DEPARTMENT OF MATERIA MEDICA, THERAPEUTICS AND PHARMACY.

PMID- 18733076
TI  - Weeds used in Medicines.

PMID- 18733077
TI  - Roster of Army Surgeons, Dept. California.

PMID- 18733078
TI  - SURGERY vs. MEDICINE.

PMID- 18733079
TI  - PREVENTIVE MEDICINES.

PMID- 18733080
TI  - ORGANIZATION AND POLITICS.

PMID- 18733081
TI  - DRUGGIST ETHICS.

PMID- 18733082
TI  - THE PURE FOOD AND DRUG BILL.

PMID- 18733083
TI  - THE EQUITABLE REFEREE CASE.

PMID- 18733084
TI  - MILK SUPPLY OF CITIES.

PMID- 18733085
TI  - NASTY FRAUD.

PMID- 18733086
TI  - THE REPUTABLE MANUFACTURERS.

PMID- 18733087
TI  - THE HOUSE OF DELEGATES.

PMID- 18733088
TI  - ILLUSTRATED ADVERTISEMENTS.

PMID- 18733089
TI  - SUGGESTIONS ARE WELCOME.

PMID- 18733090
TI  - SANITARY CONFERENCE.

PMID- 18733091
TI  - President's Address-What Should Be the Physician's Position in the Body Politic?

PMID- 18733092
TI  - Address in Surgery-Surgical Treatment of Chronic Dysentery.

PMID- 18733093
TI  - Tuberculosis of the Mammary Gland.

PMID- 18733094
TI  - Killian's Radical Operation.

PMID- 18733095
TI  - PRESCRIBING PROPRIETARIES.

PMID- 18733096
TI  - Multiplication of Bulletins.

PMID- 18733097
TI  - The Rat and His Parasites.

PMID- 18733099
TI  - Deaths.

PMID- 18733098
TI  - Value of Municipal Laboratories.

PMID- 18733100
TI  - Good Courses at Summer Session.

PMID- 18733101
TI  - Medical "Literature".

PMID- 18733103
TI  - Prescribe Intelligently.

PMID- 18733102
TI  - Plague Case 119.

PMID- 18733104
TI  - Recent Advances and Investigations in Rhinology and Otology.

PMID- 18733105
TI  - Torticollis and Spinal Curvature Due to Eye-Strain.

PMID- 18733106
TI  - American Neurological Association.

PMID- 18733108
TI  - Death From Wood Alcohol.

PMID- 18733107
TI  - Congress of Ophthalmology.

PMID- 18733109
TI  - Next Meeting State Society.

PMID- 18733110
TI  - Constitution and By-Laws.

PMID- 18733112
TI  - Association Journals.

PMID- 18733111
TI  - Assessment, 1904-05.

PMID- 18733113
TI  - Synthetic Remedies.

PMID- 18733114
TI  - Unauthorized Publications.

PMID- 18733116
TI  - Requests Opinions.

PMID- 18733115
TI  - Revised Constitution.

PMID- 18733117
TI  - Alcohol in Nostrums.

PMID- 18733118
TI  - The Active Principle of the Adrenal Gland: What Name Shall be Given to it?

PMID- 18733119
TI  - Scurvy in Infants.

PMID- 18733120
TI  - MEXICO DESIRES PURE FOOD AND DRUGS.

PMID- 18733121
TI  - Pure Food Law.

PMID- 18733122
TI  - The Rat and His Parasites.

PMID- 18733123
TI  - NEW BUILDING FOR BELLEVUE HOSPITAL.

PMID- 18733124
TI  - Inert Preparation of Digitalis.

PMID- 18733125
TI  - Alcohol in Patent Medicines.

PMID- 18733127
TI  - DEATHS.

PMID- 18733126
TI  - A WORD FROM DR. TEABY.

PMID- 18733128
TI  - A Case of Gall Stones.

PMID- 18733130
TI  - A. M. A. Meeting.

PMID- 18733129
TI  - SYNONYMS.

PMID- 18733131
TI  - State Journals.

PMID- 18733132
TI  - Portland Meeting.

PMID- 18733133
TI  - Hall of Exhibits.

PMID- 18733134
TI  - Anonymous Communication.

PMID- 18733135
TI  - Sad End.

PMID- 18733136
TI  - 1904 Register.

PMID- 18733137
TI  - Important Decision(North Carolina).

PMID- 18733138
TI  - Medical Act Sustained by the Supreme Court.

PMID- 18733139
TI  - The San Francisco Board of Health and the Milk Supply.

PMID- 18733140
TI  - To Enforce the Law.

PMID- 18733141
TI  - Text of Supreme Court's Decision on Sustaining Medical Act.

PMID- 18733142
TI  - Some Reflections on State Examining Boards.

PMID- 18733143
TI  - Cases of Prostatic Calculi.

PMID- 18733144
TI  - Malarial Nephritis.

PMID- 18733145
TI  - Pathology and Its Relation to Therapeutics.

PMID- 18733146
TI  - Report of Committee on Medical Education and Legislation.

PMID- 18733147
TI  - Acute Gastro-Enteritis.

PMID- 18733148
TI  - Plague in Check.

PMID- 18733150
TI  - Medico-Legal Responsibilities of the Physician in Cases Where Insanity is Alleged
      as a Defense.

PMID- 18733149
TI  - Complications and Sequelae of Measles.

PMID- 18733151
TI  - Rickets and Proprietary Infant Foods.

PMID- 18733152
TI  - Notice to County Secretaries.

PMID- 18733153
TI  - Death.

PMID- 18733154
TI  - Table of Pharmaceutical Synonyms.

PMID- 18733155
TI  - A. M. A. Officers.

PMID- 18733156
TI  - Eliminate the Quacks.

PMID- 18733157
TI  - A. M. A. Trustees.

PMID- 18733158
TI  - Inert Digitalis.

PMID- 18733159
TI  - A. M. A. Financial Statement.

PMID- 18733160
TI  - State Journals.

PMID- 18733161
TI  - Alcohol Nostrums.

PMID- 18733163
TI  - Value of Big Game.

PMID- 18733162
TI  - Contract Practice.

PMID- 18733164
TI  - Hospital Nurses' Association.

PMID- 18733166
TI  - Preparations of Digitalis.

PMID- 18733165
TI  - Army Medical Service.

PMID- 18733167
TI  - Preliminary Report on Peculiar Infection of Mouth and Throat.

PMID- 18733168
TI  - Illustrative Cases Myelogenous Leukemia-Preliminary Report.

PMID- 18733169
TI  - Concretio-Pericardii Cum Corde: Report of a Case.

PMID- 18733170
TI  - Tendon Transplantation, with Report of a Case.

PMID- 18733171
TI  - Intestinal Obstruction, Report of Three Unusual Cases.

PMID- 18733173
TI  - Uretero-Cystostomy, with Report of Case.

PMID- 18733172
TI  - Surgical Anatomy of the Inguinal Canal.

PMID- 18733174
TI  - Innervation of the Heart and Use of Cardiac Stimulants in Treatment of Shock.

PMID- 18733176
TI  - Synonyms.

PMID- 18733175
TI  - Determination of Functional Capacity of Kidneys, Special Reference to Kidney
      Surgery.

PMID- 18733177
TI  - Tuberculosis Commission.

PMID- 18733178
TI  - Advertising "Promotes".

PMID- 18733180
TI  - "Everybody's" Advertising.

PMID- 18733179
TI  - Lay Spasm in Advertising.

PMID- 18733182
TI  - Righteous Indignation.

PMID- 18733181
TI  - Serum for Snake Venom.

PMID- 18733183
TI  - City Milk Standard.

PMID- 18733184
TI  - The Nostrum and The Mail.

PMID- 18733185
TI  - The Card Register.

PMID- 18733186
TI  - Fraudulent Book Agent.

PMID- 18733187
TI  - Examiners and the Law.

PMID- 18733188
TI  - Commendable Cooperation.

PMID- 18733189
TI  - Nostrums and Quacks.

PMID- 18733190
TI  - Lane Lectures.

PMID- 18733191
TI  - Moral Insanity.

PMID- 18733192
TI  - Boric Acid Preservatives.

PMID- 18733193
TI  - July August Examinations.

PMID- 18733194
TI  - We Need Your Help.

PMID- 18733196
TI  - Role of General Practitioner in Prevention of Consumption.

PMID- 18733195
TI  - Report Tuberculosis Committee.

PMID- 18733198
TI  - Healed and Quiescent Pulmonary Tuberculosis.

PMID- 18733197
TI  - Sanatoria for Pulmonary Tuberculosis.

PMID- 18733199
TI  - Mules Operation.

PMID- 18733201
TI  - The "Good Things" We Are!

PMID- 18733200
TI  - Operative Fistulae of the Male Urethra.

PMID- 18733202
TI  - Symptoms of Glaucoma.

PMID- 18733203
TI  - International Congress.

PMID- 18733204
TI  - Please Help.

PMID- 18733205
TI  - A. M. A. Financial Statement.

PMID- 18733206
TI  - Inert Drugs.

PMID- 18733207
TI  - INTERNATIONAL CONGRESS OF MEDICINE.

PMID- 18733208
TI  - State Examinations, July-August.

PMID- 18733210
TI  - Child Study Congress.

PMID- 18733209
TI  - University of California, Dental Department.

PMID- 18733212
TI  - Deaths.

PMID- 18733211
TI  - Lane Medical Library.

PMID- 18733214
TI  - Post Office and Fraudulent Medicines.

PMID- 18733213
TI  - Nostrum: Foe of Rational Medicine.

PMID- 18733215
TI  - Starvation Fees in England.

PMID- 18733216
TI  - "Science" of Osteopathy.

PMID- 18733217
TI  - Hydrotherapy in Rheumatism.

PMID- 18733218
TI  - Total Laryngectomy.

PMID- 18733219
TI  - THE PRESIDIO GENERAL HOSPITAL.

PMID- 18733220
TI  - Intelligent Health Board.

PMID- 18733221
TI  - To County Secretaries.

PMID- 18733222
TI  - Facetious Criticism.

PMID- 18733223
TI  - To Members in Oregon.

PMID- 18733224
TI  - Impersonal Criticism.

PMID- 18733225
TI  - The New Register.

PMID- 18733226
TI  - Danger Ahead.

PMID- 18733227
TI  - Quacks as Examiners.

PMID- 18733229
TI  - Serum Test for Blood.

PMID- 18733228
TI  - Good Work.

PMID- 18733231
TI  - A Curious Condition.

PMID- 18733230
TI  - Education Useless.

PMID- 18733232
TI  - Another State Journal.

PMID- 18733233
TI  - Inflammation of the Appendices Epiploicae.

PMID- 18733234
TI  - Conservative Treatment of Acute Appendicitis.

PMID- 18733235
TI  - Acute Suppurative Appendicitis Treated by Ochsner Method.

PMID- 18733236
TI  - Action of Saline Purgatives.

PMID- 18733237
TI  - Epinephrin.

PMID- 18733238
TI  - Canadian Medical Association.

PMID- 18733239
TI  - Oregon State Medical Association.

PMID- 18733240
TI  - State Board Examination, October.

PMID- 18733241
TI  - State Nurses Association.

PMID- 18733242
TI  - Misapprehension of Facts.

PMID- 18733243
TI  - Some Mechanical Aspects of Spinal Curvature.

PMID- 18733245
TI  - Deaths.

PMID- 18733244
TI  - Herzstein Lectures.

PMID- 18733246
TI  - Pernicious Malarial Fever.

PMID- 18733247
TI  - Resolutions on Nostrums.

PMID- 18733248
TI  - Alcohol and Narcotics.

PMID- 18733249
TI  - Synonyms.

PMID- 18733250
TI  - Another Journal.

PMID- 18733251
TI  - License Revoked.

PMID- 18733252
TI  - Valuable Contempt.

PMID- 18733253
TI  - The Case of Diddle.

PMID- 18733254
TI  - Another Conviction.

PMID- 18733256
TI  - The Lay Treater.

PMID- 18733255
TI  - Oakland and Vaccination.

PMID- 18733257
TI  - Finsen's Death.

PMID- 18733258
TI  - The Swing of the Pendulum.

PMID- 18733260
TI  - Two Notable Retirements.

PMID- 18733259
TI  - An Easy Analysis.

PMID- 18733262
TI  - Medicine Made Easy.

PMID- 18733261
TI  - Watch Them.

PMID- 18733263
TI  - Pure Food and Drug Bureau.

PMID- 18733264
TI  - A. M. A. Financial Statement.

PMID- 18733265
TI  - Suggestion Regarding Clinical Material.

PMID- 18733267
TI  - Object Accomplished.

PMID- 18733266
TI  - Druggist Question.

PMID- 18733268
TI  - A Question.

PMID- 18733270
TI  - A Case of Trigeminal Neuralgia.

PMID- 18733269
TI  - The Operative Treatment of Pes Cavus.

PMID- 18733271
TI  - Some Remarks on Hysterectomy.

PMID- 18733272
TI  - Some Wrinkles with Fehling's Test.

PMID- 18733273
TI  - Myocarditis.

PMID- 18733275
TI  - Board of Medical Examiners.

PMID- 18733274
TI  - Treatment of Typhoid: Outline of Treatment and Results in some of the Cases of
      the Palo Alto Epidemic of 1903.

PMID- 18733276
TI  - Echinococcus of the Liver.

PMID- 18733277
TI  - County Societies.

PMID- 18733278
TI  - California Academy of Medicine.

PMID- 18733280
TI  - Pan American Congress.

PMID- 18733279
TI  - San Joaquin Valley.

PMID- 18733281
TI  - Alcohol in Proprietaries.

PMID- 18733282
TI  - Utero-Sacral Ligaments.

PMID- 18733283
TI  - Synonyms.

PMID- 18733284
TI  - Second Volume.

PMID- 18733285
TI  - Facts About the Journal.

PMID- 18733286
TI  - Death Rate of San Francisco.

PMID- 18733287
TI  - Watch the Legislature.

PMID- 18733288
TI  - Cancer Commission.

PMID- 18733289
TI  - Chemicals vs. Proprietaries.

PMID- 18733290
TI  - Unkind Slander.

PMID- 18733291
TI  - Japanese Army Medical Corps.

PMID- 18733292
TI  - Corrections in Register.

PMID- 18733293
TI  - Two Aggrieved Manufacturers.

PMID- 18733294
TI  - Clinical Material.

PMID- 18733295
TI  - Board of Examiners.

PMID- 18733296
TI  - Accuracy in Medical Work.

PMID- 18733297
TI  - Contribution to Study of Varicocele.

PMID- 18733298
TI  - Treatment of Typhoid. (Concluded.).

PMID- 18733300
TI  - Posterior Gastro-Enterostomy.

PMID- 18733299
TI  - Myocarditis.

PMID- 18733301
TI  - Oakland and Vaccination.

PMID- 18733302
TI  - What Your Journal is Doing.

PMID- 18733303
TI  - Druggist Question.

PMID- 18733304
TI  - Precocious Menstruation.

PMID- 18733305
TI  - Patent Medicine Advertising.

PMID- 18733306
TI  - Watch Your Legislators.

PMID- 18733307
TI  - Stovain; New Analgesic.

PMID- 18733308
TI  - Iodothyrine; A Correction.

PMID- 18733309
TI  - As We Seem to New Jersey.

PMID- 18733311
TI  - Medical Societies-General.

PMID- 18733310
TI  - New Licentiates.

PMID- 18733312
TI  - County Societies.

PMID- 18733313
TI  - Another New Year.

PMID- 18733314
TI  - Tuberculosis Sanatoria.

PMID- 18733315
TI  - An Answer to a Question.

PMID- 18733316
TI  - Second and Fourth Positions of the Vertex.

PMID- 18733317
TI  - Appendicitis: Some Points in Its Diagnoses and Treatment From the View-point That
      Its Cause is a Strangulation Produced by Distention Behind a Ball-Valve.

PMID- 18733318
TI  - Myocarditis.

PMID- 18733320
TI  - Vaccination Foolishness.

PMID- 18733319
TI  - Chronic Otorrhea.

PMID- 18733321
TI  - Forced to Do Right.

PMID- 18733322
TI  - Just Keep Hammering.

PMID- 18733323
TI  - Surgical Treatment of Chronic Nephritis.

PMID- 18733324
TI  - Improper Use of Wood Alcohol.

PMID- 18733325
TI  - Odor Humane.

PMID- 18733327
TI  - Our Wonderful "English".

PMID- 18733326
TI  - Unity of the Medical Profession.

PMID- 18733328
TI  - San Francisco and the Quacks.

PMID- 18733329
TI  - Druggist and Physician.

PMID- 18733330
TI  - Wood-Alcohol Poisoning.

PMID- 18733332
TI  - Additions to List of Legislators.

PMID- 18733331
TI  - David and Goliath.

PMID- 18733333
TI  - Resolutions Regarding Advertising.

PMID- 18733334
TI  - Driesbach Smith.

PMID- 18733335
TI  - Electric Skin Grafting.

PMID- 18733336
TI  - National Quarantine Law.

PMID- 18733338
TI  - County Societies.

PMID- 18733337
TI  - Japan's Lesson to Us.

PMID- 18733339
TI  - Grand Prize for Pharmaceuticals.

PMID- 18733340
TI  - The Pity of It All.

PMID- 18733342
TI  - Nasty Fraud.

PMID- 18733341
TI  - Program Outlined.

PMID- 18733344
TI  - Change in Twenty Years.

PMID- 18733343
TI  - Medical Societies.

PMID- 18733345
TI  - Use of the Phorometer.

PMID- 18733346
TI  - Examinations, December.

PMID- 18733347
TI  - Registration of Nurses.

PMID- 18733348
TI  - My Son Make Money.

PMID- 18733349
TI  - Danger from Our Friends.

PMID- 18733351
TI  - Diagnosis and Management of Transverse Presentation.

PMID- 18733350
TI  - The Prevention of Tuberculosis.

PMID- 18733352
TI  - The Meeting at Riverside.

PMID- 18733353
TI  - Some Bad Legislation.

PMID- 18733354
TI  - A Few Facts.

PMID- 18733355
TI  - Micrococcus Rheumaticus.

PMID- 18733356
TI  - Tuberculosis Sanatoria.

PMID- 18733357
TI  - Dignified Editorials.

PMID- 18733358
TI  - Annals of Surgery.

PMID- 18733360
TI  - The Bacillus of Syphilis.

PMID- 18733359
TI  - Consider the Lilies.

PMID- 18733361
TI  - Surgical Interference in Tuberculosis of the Bladder.

PMID- 18733362
TI  - Prosecutions in San Francisco.

PMID- 18733363
TI  - Pathology of Glaucoma.

PMID- 18733364
TI  - Concerning Varieties and Etiology of Glaucoma.

PMID- 18733365
TI  - Treatment of Glaucoma.

PMID- 18733366
TI  - Tonsils as Portals of Infection.

PMID- 18733367
TI  - Report of Cases Simulating Grave Mastoiditis.

PMID- 18733368
TI  - Congenital Dislocation of the Hip.

PMID- 18733369
TI  - Etiology of Infantile Eclampsia.

PMID- 18733370
TI  - Posture in Treatment of Disease.

PMID- 18733371
TI  - Dangers of Proprietary-Remedy Prescribing.

PMID- 18733373
TI  - Report of a Case of Pernicious Anemia.

PMID- 18733372
TI  - Epinephrin; Especially in Asthma.

PMID- 18733375
TI  - California Medical and Surgical Reporter.

PMID- 18733374
TI  - Nurses' Journal.

PMID- 18733377
TI  - Shall I Operate?

PMID- 18733376
TI  - Condemnation of Division of Fees.

PMID- 18733378
TI  - A Manufacturer's Troubles.

PMID- 18733379
TI  - The "Internist" Foolishness.

PMID- 18733380
TI  - XVth International Congress of Medicine.

PMID- 18733382
TI  - Do Not Advertise to the Public.

PMID- 18733381
TI  - Gross Effects of Radium.

PMID- 18733383
TI  - County Societies.

PMID- 18733384
TI  - Medical Societies.

PMID- 18733385
TI  - Organization and Unity.

PMID- 18733386
TI  - New Jersey's Approval.

PMID- 18733387
TI  - The Napoleon Myth.

PMID- 18733388
TI  - Some Confusion.

PMID- 18733390
TI  - Our State Legislators.

PMID- 18733389
TI  - Rupture of Semilunar Cartilage.

PMID- 18733391
TI  - A Little History.

PMID- 18733393
TI  - Misplaced Confidence.

PMID- 18733394
TI  - Bind Your Journals.

PMID- 18733395
TI  - The Hall of Fame.

PMID- 18733396
TI  - The Uric Acid Fallacy.

PMID- 18733397
TI  - Danger in X-Ray Exposure.

PMID- 18733398
TI  - The Relation of the A. M. A. to Medical Advertising: A statement by the
      Publication Committee.

PMID- 18733400
TI  - Neurasthenia in Childhood.

PMID- 18733399
TI  - Surgical Interference in Tuberculosis of the Bladder.

PMID- 18733401
TI  - Tumors of the Kidney.

PMID- 18733403
TI  - The Effects of Tonsillotomy.

PMID- 18733402
TI  - Surgical Treatment of Chronic Tonsillitis.

PMID- 18733405
TI  - Manufacturing Pharmacists of So-called Proprietary Remedies and the Medical
      Profession.

PMID- 18733404
TI  - Some Remarks on Gonorrhea in Women.

PMID- 18733406
TI  - Flies as Carriers of Contagion.

PMID- 18733407
TI  - Aseptic Catheterization of the Urinary Passages.

PMID- 18733408
TI  - The Sanitary Needs of the State.

PMID- 18733409
TI  - Pertusis or Whooping Cough, and its Treatment.

PMID- 18733410
TI  - Adenoids.

PMID- 18733411
TI  - Mother Mary.

PMID- 18733412
TI  - Good Milk in Milwaukee.

PMID- 18733413
TI  - County Societies.

PMID- 18733414
TI  - Medical Societies.

PMID- 18733415
TI  - Course of Instruction in Public Health.

PMID- 18733416
TI  - Army Medical Corps Examinations.

PMID- 18733417
TI  - Proprietary Preparations Excluded from Norway.

PMID- 18733418
TI  - An Opinion from Virginia.

PMID- 18733419
TI  - Curious Law in Ohio.

PMID- 18733421
TI  - A New Journal.

PMID- 18733420
TI  - Anti-Tuberculosis League.

PMID- 18733423
TI  - The Canal Commission.

PMID- 18733422
TI  - Meeting at Riverside.

PMID- 18733424
TI  - Lawson and the System.

PMID- 18733425
TI  - The Friendly (?) Druggists.

PMID- 18733426
TI  - Ignorant Candidates.

PMID- 18733427
TI  - Medical Examiners.

PMID- 18733428
TI  - Tuberculosis Sanatorium.

PMID- 18733429
TI  - Have We Won the Fight?

PMID- 18733431
TI  - Amendments to the Constitution: Second Publication.

PMID- 18733430
TI  - A. M. A. Council on Pharmacy and Chemistry.

PMID- 18733432
TI  - The Rubaiyat, after Osler.

PMID- 18733433
TI  - A Consideration of Congenital Dislocation of the Hip.

PMID- 18733434
TI  - Southern California Hospitals.

PMID- 18733435
TI  - Report on Epidemic of Diphtheria.

PMID- 18733436
TI  - Post-Operative Ventral Hernia.

PMID- 18733438
TI  - Acute Delirium.

PMID- 18733437
TI  - Etiology of Locomotor Ataxia.

PMID- 18733439
TI  - Support the Board of Examiners.

PMID- 18733441
TI  - Intelligent Examination Papers.

PMID- 18733440
TI  - An Appeal to the General Practitioner.

PMID- 18733442
TI  - County Societies.

PMID- 18733443
TI  - Medical Societies.

PMID- 18733445
TI  - UNCINARIASIS, WITH REPORT OF SEVEN CASES.

PMID- 18733444
TI  - Alcoholics.

PMID- 18733446
TI  - The A. M. A. Meeting.

PMID- 18733447
TI  - Thank God!

PMID- 18733449
TI  - Insurance Examiners.

PMID- 18733448
TI  - Boards of Examiners.

PMID- 18733450
TI  - California's Invitation.

PMID- 18733451
TI  - The Cuba Commission.

PMID- 18733452
TI  - Hall of Exhibits.

PMID- 18733453
TI  - Shameless Frankness.

PMID- 18733454
TI  - The Canal Sanitation.

PMID- 18733455
TI  - The Wily Politician.

PMID- 18733456
TI  - Such a Virtue!

PMID- 18733458
TI  - Proprietaries in Present Day Prescriptions.

PMID- 18733457
TI  - A Sad Death.

PMID- 18733459
TI  - Our Present Condition.

PMID- 18733460
TI  - Tendon Surgery.

PMID- 18733462
TI  - Address of the President: Thirty-fifth Annual Meeting of the Medical Society of
      the State of California.

PMID- 18733461
TI  - The President, Frank L. Adams.

PMID- 18733463
TI  - Superlative Nerve.

PMID- 18733465
TI  - The Use of Benzoylvinyl-Diacetone-Alkamine Lactate.

PMID- 18733464
TI  - Recent Progress in Surgery of the Ear and Brain.

PMID- 18733467
TI  - To Grunsky-Verb Active.

PMID- 18733466
TI  - A Case of Primary Carcinoma of the Lung.

PMID- 18733468
TI  - Proposed Amendment to Constitution: First Publication.

PMID- 18733469
TI  - Tendon Transplantation.

PMID- 18733470
TI  - Nephrotomy for Stone in the Kidney.

PMID- 18733471
TI  - Recurrent Eclampsia.

PMID- 18733472
TI  - Osteomalacia.

PMID- 18733473
TI  - Fractures of the Anatomical Neck of the Humerus.

PMID- 18733475
TI  - Druggists' Working Time Limit.

PMID- 18733474
TI  - A Defender of Secret Nostrums.

PMID- 18733476
TI  - Another Illegal Practitioner Gone.

PMID- 18733477
TI  - Medical Societies.

PMID- 18733478
TI  - County Societies.

PMID- 18733479
TI  - Cheap Insurance Examinations.

PMID- 18733480
TI  - Necessary Work in Politics.

PMID- 18733482
TI  - Election of Officers.

PMID- 18733481
TI  - California: Some Words of Truth.

PMID- 18733483
TI  - Tuberculosis Notification.

PMID- 18733484
TI  - The County Societies.

PMID- 18733486
TI  - Honest Medicines.

PMID- 18733485
TI  - The Simple Reason Why.

PMID- 18733487
TI  - Wasting Material.

PMID- 18733488
TI  - Tendon Transplantation.

PMID- 18733490
TI  - Report of Three Cases of Infra and One of Supra-Diaphragmatic Aortic Aneurism.

PMID- 18733489
TI  - Sudden Change.

PMID- 18733491
TI  - Analysis of Fifteen Cases of Operation for Cancer of the Breast.

PMID- 18733492
TI  - Notes on State Hospital Sanitation.

PMID- 18733493
TI  - Medical Inspection of Schools.

PMID- 18733494
TI  - My Experience With Medullary Narcosis.

PMID- 18733495
TI  - A Plea for the Druggist.

PMID- 18733496
TI  - Why Should Roentgology Be Practiced Only by the Physician?

PMID- 18733498
TI  - Radical Mastoid Operation for Chronic Suppuration of the Middle Ear.

PMID- 18733499
TI  - Clinical Findings Usually Overlooked in Mucomembranous Enterocolitis.

PMID- 18733497
TI  - Fatty Degeneration of the Heart.

PMID- 18733501
TI  - Cooper College Commencement.

PMID- 18733500
TI  - Osteomalacia: Addenda.

PMID- 18733503
TI  - Report of Council.

PMID- 18733502
TI  - Report of Secretary.

PMID- 18733504
TI  - Some Personal Impressions.

PMID- 18733505
TI  - Delegates in Attendance.

PMID- 18733506
TI  - County Societies.

PMID- 18733507
TI  - American Medical Association Journal.

PMID- 18733508
TI  - William Hammond.

PMID- 18733510
TI  - The A. M. A. Finances.

PMID- 18733509
TI  - Beware of Swindlers.

PMID- 18733512
TI  - Council on Pharmacy.

PMID- 18733511
TI  - State Journals.

PMID- 18733513
TI  - Torture in California.

PMID- 18733514
TI  - A Good Suggestion.

PMID- 18733515
TI  - Insurance Examinations.

PMID- 18733516
TI  - The Rules of the Council.

PMID- 18733517
TI  - A Word of Apology.

PMID- 18733518
TI  - Examination by State Board.

PMID- 18733519
TI  - Proprietary Pharmacists and State Medical Association Journals.

PMID- 18733520
TI  - Astonishing Ignorance.

PMID- 18733521
TI  - Proprietary Therapeutics.

PMID- 18733522
TI  - A Medico Legal Case.

PMID- 18733523
TI  - Is the Health of Los Angeles Menaced by Pulmonary Tuberculosis?

PMID- 18733524
TI  - Adams-Stokes Syndrome, With Report of Two Cases.

PMID- 18733525
TI  - Use of Hyoscine-Hydrobromate in the Treatment of Morphine Habit, With Report of
      Cases.

PMID- 18733526
TI  - Uncinariasis in California, Based on Observation of Sixty-two Cases.

PMID- 18733527
TI  - Adolescence in Girls.

PMID- 18733528
TI  - Practical Method for the Determination of the Defects of the Special Senses in
      School Children.

PMID- 18733529
TI  - The Conveyance of Syphilitic Infection by Medical Men.

PMID- 18733530
TI  - A Case of Human Glanders.

PMID- 18733531
TI  - Typhoid Infection of the Hip Joint. Report of a Case.

PMID- 18733532
TI  - San Francisco Garden of Medicinal Plants.

PMID- 18733533
TI  - Unauthorized Use of Names.

PMID- 18733534
TI  - Remote Effects of Typhoid Fever Upon the Bones and Joints.

PMID- 18733536
TI  - County Societies.

PMID- 18733535
TI  - Council on Pharmacy and Chemistry A. M. A: American Medical Association.

PMID- 18733538
TI  - Unfortunate Accidents.

PMID- 18733537
TI  - Medical Societies.

PMID- 18733540
TI  - Pharmaceutical Congress.

PMID- 18733539
TI  - Resignation of Dr. Wilbur.

PMID- 18733541
TI  - Heavy Sentence for Illegal Practitioner.

PMID- 18733542
TI  - Nostrum Question.

PMID- 18733543
TI  - The Surgical Association.

PMID- 18733544
TI  - The A. M. A. Meeting.

PMID- 18733545
TI  - New Officers of the A. M. A.

PMID- 18733547
TI  - The A. M. A. Directory.

PMID- 18733546
TI  - Hall of Exhibits.

PMID- 18733548
TI  - Hope for the Future.

PMID- 18733549
TI  - The New U. S. Pharmacopeia.

PMID- 18733550
TI  - Undesirable Sympathy.

PMID- 18733551
TI  - Importance of Accuracy.

PMID- 18733552
TI  - The American Surgical Association.

PMID- 18733553
TI  - Diagnosis of Typhoid Fever, a Paper Addressed to the Country Practitioner.

PMID- 18733554
TI  - Routine Treatment and Complications of Typhoid Fever.

PMID- 18733556
TI  - The Accessory Treatment of Typhoid Fever.

PMID- 18733555
TI  - Surgery (Immediate) of Perforated Typhoid Ulcer, with Report of Case.

PMID- 18733557
TI  - The Prevention of Disease-Its Present Need.

PMID- 18733558
TI  - Tubular Diarrhea or Membranous Colic.

PMID- 18733559
TI  - Practical Application of Functional Diagnosis in Unilateral Kidney Lesions.

PMID- 18733561
TI  - Physicians and Quack Remedies.

PMID- 18733560
TI  - Tetanus.

PMID- 18733562
TI  - A Criticism Which is a Compliment.

PMID- 18733563
TI  - County Societies.

PMID- 18733564
TI  - Medical Societies.

PMID- 18733565
TI  - Medical Journals.

PMID- 18733566
TI  - A Worthy Examiner.

PMID- 18733567
TI  - Medical Frauds.

PMID- 18733569
TI  - An Official Document.

PMID- 18733568
TI  - Beware of Fakes.

PMID- 18733570
TI  - Do Not Forget.

PMID- 18733571
TI  - Yellow Fever.

PMID- 18733573
TI  - Tuberculosis Notification.

PMID- 18733572
TI  - Unfortunate Complication.

PMID- 18733574
TI  - The Course of Proprietaries.

PMID- 18733576
TI  - State Journals.

PMID- 18733575
TI  - The X-Ray in Cancer.

PMID- 18733577
TI  - The Lane Lectures.

PMID- 18733578
TI  - Very Important Changes.

PMID- 18733579
TI  - Reception to Dr. Musser.

PMID- 18733580
TI  - Unity, Peace and Concord: Abstract of a Farewell Address to the Medical
      Profession of the United States.

PMID- 18733581
TI  - Clinical Features of Gallbladder and Gall Duct Affections.

PMID- 18733583
TI  - Report of the Work of the Board of Examiners.

PMID- 18733582
TI  - Preliminary Education.

PMID- 18733584
TI  - Dinner to Sir Patrick Manson.

PMID- 18733586
TI  - Indications for Roentgotherapy.

PMID- 18733585
TI  - Remarks of Uses and Abuses of the X-Ray.

PMID- 18733587
TI  - Syphilitic Keratodermia; Report of a Case Simulating Erythema Keratodes or
      "Brookes's Disease.".

PMID- 18733588
TI  - A Case of Poisoning from Ceanothus Velutinus, Resembling Rhus Poisoning.

PMID- 18733589
TI  - Publication Committee on Advertising.

PMID- 18733590
TI  - California Public Health Association.

PMID- 18733591
TI  - Notification of Tuberculosis.

PMID- 18733593
TI  - County Societies.

PMID- 18733592
TI  - New Terms.

PMID- 18733594
TI  - Publishing Medical Journals for Private Profit or for the Profession.

PMID- 18733595
TI  - McCormack on Organization.

PMID- 18733596
TI  - Theory and Practice.

PMID- 18733597
TI  - Telephone Service.

PMID- 18733598
TI  - New Orleans Death Rate.

PMID- 18733599
TI  - Directly Insulting.

PMID- 18733600
TI  - What's in a Name?

PMID- 18733601
TI  - A Last Word on Accuracy.

PMID- 18733603
TI  - Keep at it.

PMID- 18733602
TI  - Official Register.

PMID- 18733604
TI  - Some Good Suggestions.

PMID- 18733605
TI  - Use the Office.

PMID- 18733606
TI  - Locations for Sale.

PMID- 18733607
TI  - Next!

PMID- 18733608
TI  - Murdered by Advertisement.

PMID- 18733609
TI  - Inefficient Refracting.

PMID- 18733610
TI  - President's Address, Pacific Railway Surgeons.

PMID- 18733612
TI  - Early Operation of Gall-Stone Disease.

PMID- 18733611
TI  - "Patent" and Secret Proprietary Medicines.

PMID- 18733613
TI  - Surgical Treatment of Pancreatic Complications in Gall-Stone Disease.

PMID- 18733614
TI  - More Simple Technic in Herniotomy.

PMID- 18733615
TI  - Cerebral Abscess of Otitic Origin.

PMID- 18733617
TI  - State Board of Health.

PMID- 18733616
TI  - Erythema Multiformis; Case Report.

PMID- 18733618
TI  - Spastic Paraplegia.

PMID- 18733619
TI  - Fibro-Myoma of the Uterus.

PMID- 18733620
TI  - Adenoids from Standpoint of Parent.

PMID- 18733621
TI  - Examinations in Texas.

PMID- 18733622
TI  - Acute Chylous Mesenteric Cyst.

PMID- 18733623
TI  - Chronic Suppuration of the Middle Ear.

PMID- 18733624
TI  - Interdental Splint for Fractures of the Jaw.

PMID- 18733625
TI  - Misuse of Atropine.

PMID- 18733626
TI  - New Birth Certificate.

PMID- 18733627
TI  - Wimer Suit.

PMID- 18733628
TI  - Atypical Rheumatism; Case Report.

PMID- 18733630
TI  - County Societies.

PMID- 18733629
TI  - Linguistic Crimes.

PMID- 18733632
TI  - California Academy of Medicine.

PMID- 18733631
TI  - Poppy Alkaloids.

PMID- 18733633
TI  - Correction, July-August Examinations.

PMID- 18733634
TI  - Mississippi Valley Medical Association.

PMID- 18733636
TI  - Fees for Examinations.

PMID- 18733635
TI  - Examinations in Obstetrics.

PMID- 18733638
TI  - Advertising Pages.

PMID- 18733637
TI  - Medical Editors.

PMID- 18733639
TI  - Collier's on Nostrums.

PMID- 18733640
TI  - San Francisco Chronicle.

PMID- 18733641
TI  - The Meeting Next Year.

PMID- 18733642
TI  - Pepto-Mangan.

PMID- 18733643
TI  - Yellow Fever.

PMID- 18733644
TI  - The Ones Enmeshed.

PMID- 18733645
TI  - Dr. McCormack's Addresses on Organization.

PMID- 18733646
TI  - Scientific Work Misrepresented and Commercialized.

PMID- 18733647
TI  - Pharmacology.

PMID- 18733648
TI  - The Medical Record and Propaganda Against Nostrums.

PMID- 18733650
TI  - Medical Advertising.

PMID- 18733649
TI  - Herzstein Lecture No. I. The Toxic Agent in Gastro-Intestinal Autointoxication.

PMID- 18733652
TI  - A Case of Pseudo-Hypertrophic Muscular Dystrophy.

PMID- 18733651
TI  - Excision of the Cervical Portion of the Esophagus.

PMID- 18733653
TI  - Trypanosome and Its Relation to Certain Diseases.

PMID- 18733654
TI  - The Pathology and Treatment of Morphinism.

PMID- 18733655
TI  - Closure of Tracheotomy Wounds.

PMID- 18733657
TI  - A Case of Hydro-Nephrosis of Movable Kidney.

PMID- 18733656
TI  - Remarks on the Treatment of Compound Fractures.

PMID- 18733658
TI  - Nephro-Phonotoscope and Ureto-Renal Calculi.

PMID- 18733659
TI  - Patent Medicines: A Good Suggestion.

PMID- 18733660
TI  - Thyroid Diseases in California.

PMID- 18733661
TI  - Anesthesia in Ear, Throat and Nose Operations.

PMID- 18733662
TI  - When to Operate Upon Uterine Fibromyomata: Myomectomy.

PMID- 18733663
TI  - Para-Typhoid Infection.

PMID- 18733664
TI  - Mesenteric Thrombosis; Report of Case.

PMID- 18733665
TI  - A New Journal.

PMID- 18733666
TI  - Education in the Orient.

PMID- 18733667
TI  - State Control of Tuberculosis.

PMID- 18733668
TI  - Death of Dr. Todd.

PMID- 18733669
TI  - County Societies.

PMID- 18733670
TI  - Cheap Fees.

PMID- 18733671
TI  - Typhoid vs. Tuberculosis.

PMID- 18733672
TI  - Death of Dr. Mules.

PMID- 18733673
TI  - The Society of Social and Moral Prophylaxis.

PMID- 18733674
TI  - Medical Societies.

PMID- 18733675
TI  - Drugs and Diazo Reaction.

PMID- 18733676
TI  - Exstrophy of the Bladder.

PMID- 18733677
TI  - Preliminary Report on Cells Found in Yellow Fever.

PMID- 18733678
TI  - Collier's Weekly.

PMID- 18733679
TI  - Medical Laws.

PMID- 18733680
TI  - Alcoholic Nostrums.

PMID- 18733681
TI  - Graft.

PMID- 18733682
TI  - Billings' Paper.

PMID- 18733683
TI  - Unblushing Impudence.

PMID- 18733684
TI  - Those Fees.

PMID- 18733685
TI  - Dr. McCormack's Addresses on Organization-Continued.

PMID- 18733686
TI  - Dr. Edith Jane Claypole vs. Board of Medical Examiners.

PMID- 18733687
TI  - The Secret Nostrum Evil.

PMID- 18733688
TI  - Communications.

PMID- 18733689
TI  - Are We Owned by the Nostrums?

PMID- 18733690
TI  - Medical Laws and the Influences that Mold Them.

PMID- 18733691
TI  - Herzstein Lecture No. II. The Theory of Disinfection.

PMID- 18733692
TI  - Methods Employed in Eradicating Infectious Disease in Chinese Quarter of San
      Francisco.

PMID- 18733693
TI  - Medical Treatment of Diseases of Gall-Bladder and Ducts.

PMID- 18733694
TI  - Stitch Hole Abscess.

PMID- 18733696
TI  - The Mission and Function of the Local Medical Journal.

PMID- 18733695
TI  - Extra Uterine Pregnancy.

PMID- 18733697
TI  - Well-Deserved Honor.

PMID- 18733698
TI  - Secret Remedies.

PMID- 18733699
TI  - Congratulations to Missouri.

PMID- 18733700
TI  - Alcohol in Patent Medicines.

PMID- 18733701
TI  - Objectionable Advertising.

PMID- 18733703
TI  - County Societies.

PMID- 18733702
TI  - Uterine Fibroids Complicating Labor.

PMID- 18733704
TI  - Medical Societies.

PMID- 18733705
TI  - Extravagant Claims for Hyoscine in the Treatment of Drug Addictions.

PMID- 18733706
TI  - Our Position.

PMID- 18733707
TI  - International Congress for Tuberculosis.

PMID- 18733708
TI  - Nostrums Are Beginning to Get Their Due.

PMID- 18733710
TI  - A New Year.

PMID- 18733709
TI  - Requiescat in Pace.

PMID- 18733711
TI  - Collier's on Acetanilid.

PMID- 18733712
TI  - Herzstein Lecture No. III. The Relation of the Nitrogenous and the Carbonous
      Metabolism in Disease.

PMID- 18733713
TI  - The Spirocheta Pallida.

PMID- 18733715
TI  - A Nice Business.

PMID- 18733714
TI  - The Relation of Bacteria to the Development of Gall-Stones-A Report of
      Experimental Studies with a Review of the Literature.

PMID- 18733717
TI  - Further Data on Chest Shape in Tuberculosis.

PMID- 18733716
TI  - Radical Cure of Umbilical Hernia.

PMID- 18733718
TI  - Medical Societies.

PMID- 18733719
TI  - A Simple Illustration.

PMID- 18733721
TI  - Druggist or Pharmacist?

PMID- 18733720
TI  - Some Progress.

PMID- 18733722
TI  - County Societies.

PMID- 18733724
TI  - The A. M. A. Directory.

PMID- 18733723
TI  - Communication: A Reply to Dr. Pettey.

PMID- 18733725
TI  - Dr. McCormack's Addresses on Organization-(Concluded).

PMID- 18733726
TI  - Proprietary Association of America.

PMID- 18733727
TI  - Crying Evil.

PMID- 18733728
TI  - Lodge Practice.

PMID- 18733729
TI  - Report from Dr. McCormack.

PMID- 18733730
TI  - Defrauding Physicians.

PMID- 18733732
TI  - Unity in New York.

PMID- 18733731
TI  - Will It Blow Over?

PMID- 18733734
TI  - The Status of Organization Work in California.

PMID- 18733733
TI  - Small Errors.

PMID- 18733735
TI  - Silly Reports.

PMID- 18733736
TI  - A Weakly (?) Journal.

PMID- 18733737
TI  - A Great Work. What a County Society May Do.

PMID- 18733738
TI  - Asphyxia Neonatorum. New Method of Resuscitation.

PMID- 18733739
TI  - Tuberculosis of Mesenteric Lymph Glands. Symptoms of Intussusception
      Necessitating Resection of Intestine.

PMID- 18733740
TI  - Contract Practice.

PMID- 18733741
TI  - Herzstein Lecture No. IV. The Value of Kryoscopic Investigations for Pathology
      and Diagnosis.

PMID- 18733742
TI  - Some Remarks Concerning the Conservative Treatment of Severe Ocular Injuries.

PMID- 18733743
TI  - Report of Committee on Vital Statistics.

PMID- 18733744
TI  - Certificates Revoked.

PMID- 18733745
TI  - Preliminary Report on Phlebo-Sclerosis.

PMID- 18733746
TI  - Widening of the Pelvis by Pubiotomy.

PMID- 18733747
TI  - SEMI-ANNUAL ADDRESS OF PRESIDENT OF SANTA CLARA COUNTY MEDICAL SOCIETY.

PMID- 18733749
TI  - RECENT COMPLETE TEARS OF THE PERINEUM.

PMID- 18733748
TI  - THE PROPRIETY OF CHOLECYSTECTOMY AS AN INITIAL PROCEDURE IN GALL BLADDER SURGERY.

PMID- 18733750
TI  - MERCURIAL INJECTIONS IN SYPHILIS.

PMID- 18733751
TI  - U. S. Pharmacopeial Business Affairs.

PMID- 18733752
TI  - Dr. Pottenger's Name Misused.

PMID- 18733754
TI  - UNDRAWN POULTRY AND FISH.

PMID- 18733753
TI  - GEORGE CHISMORE, M. D.

PMID- 18733755
TI  - SAN FRANCISCO SOCIETY OF EYE, EAR, NOSE AND THROAT SURGEONS.

PMID- 18733757
TI  - Insanity and Tuberculosis.

PMID- 18733756
TI  - XVth International Congress of Medicine-(Lisbon, 19-26 April, 1906).

PMID- 18733759
TI  - COUNTY SOCIETIES.

PMID- 18733758
TI  - Gonorrhea and Enlarged Prostate.

PMID- 18733760
TI  - COOPER SCIENCE CLUB.

PMID- 18733761
TI  - Contamination of Water Supplies.

PMID- 18733763
TI  - Thomas Ross (Deceased).

PMID- 18733762
TI  - Medical Societies.

PMID- 18733764
TI  - The Task of the Weekly Medical Journal.

PMID- 18733765
TI  - County Societies.

PMID- 18733766
TI  - Snake Venom a Product of Digestion.

PMID- 18733768
TI  - Sacramento's New Ordinance.

PMID- 18733767
TI  - Scopolamine-Morphine Anesthesia.

PMID- 18733769
TI  - State Journals.

PMID- 18733770
TI  - Rates to Boston.

PMID- 18733771
TI  - Some Others.

PMID- 18733772
TI  - Other Changes.

PMID- 18733773
TI  - Curious Conditions.

PMID- 18733774
TI  - Good Work.

PMID- 18733775
TI  - Lodge Practice.

PMID- 18733776
TI  - Dangerous Prescriptions.

PMID- 18733777
TI  - Still More.

PMID- 18733778
TI  - Weekly Meetings.

PMID- 18733779
TI  - How You Can Help.

PMID- 18733780
TI  - Valuable Ordinance.

PMID- 18733781
TI  - The Differentiation of the (so-called) Seborrheic Conditions of the Scalp.

PMID- 18733783
TI  - New Etiology and Treatment of Chronic Bronchitis.

PMID- 18733782
TI  - Supreme Court Decisions.

PMID- 18733784
TI  - The Elimination of the Nostrum Traffic an Evident Duty of American Physicians.

PMID- 18733785
TI  - Report of Committee on Vital Statistics.

PMID- 18733786
TI  - Indications and Contra-Indications for Intra-Laryngeal Operation in Tuberculosis
      of Larynx.

PMID- 18733787
TI  - Partial Reduction in Dislocations of the Shoulder.

PMID- 18733788
TI  - The Spirocheta Pallida (Treponema Pallida).

PMID- 18733790
TI  - Army Medical Corps Examinations.

PMID- 18733789
TI  - Repair of Lacerations.

PMID- 18733791
TI  - Medical Support of Nostrums.

PMID- 18733792
TI  - Gastric and Duodenal Ulcers.

PMID- 18733793
TI  - Official Insult.

PMID- 18733795
TI  - Better Work.

PMID- 18733794
TI  - The Big Thieves.

PMID- 18733796
TI  - Proprietary Association.

PMID- 18733797
TI  - Good Bill.

PMID- 18733799
TI  - Let Us Help.

PMID- 18733798
TI  - The Next Legislature.

PMID- 18733801
TI  - Pure Food.

PMID- 18733800
TI  - Frauds in Medicines.

PMID- 18733802
TI  - Attack Our Law.

PMID- 18733803
TI  - Proposed Amendment to Constitution: Second Publication.

PMID- 18733804
TI  - A Typical Example.

PMID- 18733805
TI  - Our Censorious Contemporaries.

PMID- 18733806
TI  - Motor Complications of Herpes Zoster.

PMID- 18733807
TI  - Educational Treatment of the Neurasthenic and Hysterical Condition.

PMID- 18733808
TI  - Demonstration of Dilatations of the Descending Aorta.

PMID- 18733809
TI  - Preliminary Report on Epididymotomy.

PMID- 18733810
TI  - Pityriasis Rosea.

PMID- 18733811
TI  - Pathology and Treatment of Tetanus.

PMID- 18733813
TI  - Gastroenteric Autointoxication.

PMID- 18733812
TI  - Laboratory Equipment for the General Practitioner.

PMID- 18733814
TI  - Board of Examiners Commended.

PMID- 18733815
TI  - Courses Offered Tarrant County Medical Society.

PMID- 18733816
TI  - Resolutions on Nostrums.

PMID- 18733817
TI  - Encouraging.

PMID- 18733818
TI  - Insurance Fees.

PMID- 18733820
TI  - Members of the Proprietary Association of America.

PMID- 18733819
TI  - Philanthropic Physicians.

PMID- 18733821
TI  - County Societies.

PMID- 18733822
TI  - Fraudulent Subscriptions.

PMID- 18733824
TI  - A Denial.

PMID- 18733823
TI  - Past Presidents.

PMID- 18733825
TI  - Enucleation Questioned.

PMID- 18733826
TI  - Small Fees Dangerous.

PMID- 18733827
TI  - Medical Societies.

PMID- 18733828
TI  - Proprietary Medicine from the Pharmacist's Standpoint.

PMID- 18733829
TI  - Convictions in Los Angeles.

PMID- 18733830
TI  - THREATENED LIBEL SUIT.

PMID- 18733831
TI  - A SAD GREETING.

PMID- 18733832
TI  - HELP NEEDED.

PMID- 18733833
TI  - STATE SOCIETY.

PMID- 18733834
TI  - THE REAL SUFFERERS.

PMID- 18733835
TI  - BUSINESS OF THE SOCIETY.

PMID- 18733837
TI  - Our New Office.

PMID- 18733836
TI  - OUR POLICY.

PMID- 18733839
TI  - Please Help.

PMID- 18733838
TI  - Whose Fault?

PMID- 18733840
TI  - Much Rake.

PMID- 18733841
TI  - Board of Examiners.

PMID- 18733842
TI  - Is This Right?

PMID- 18733843
TI  - Pure Foods and Drugs.

PMID- 18733844
TI  - Much Yelping.

PMID- 18733846
TI  - Our Share.

PMID- 18733845
TI  - The New Directory.

PMID- 18733847
TI  - The A. M. A. Officers.

PMID- 18733848
TI  - Mailing List.

PMID- 18733849
TI  - Some More Impudence.

PMID- 18733850
TI  - President's Address.

PMID- 18733851
TI  - How to Say It.

PMID- 18733852
TI  - Report of Council.

PMID- 18733853
TI  - Report of Secretary.

PMID- 18733855
TI  - Druggists and Nostrums.

PMID- 18733854
TI  - Report of Tuberculosis Committee: Third Annual Report of the Tuberculosis
      Committee of the Medical Society of the State of California.

PMID- 18733856
TI  - Abdominal Exploration.

PMID- 18733858
TI  - Foot-Ball Injuries.

PMID- 18733857
TI  - Liver Infection from Appendicitis.

PMID- 18733859
TI  - Observation of Patients After Operation on Pelvis Viscera.

PMID- 18733860
TI  - General Diseases as a Cause of Diseases of the Eye.

PMID- 18733861
TI  - Minutes of the House of Delegates, April, 1906.

PMID- 18733862
TI  - County Societies.

PMID- 18733863
TI  - Lane Lectures.

PMID- 18733864
TI  - San Francisco Polyclinic.

PMID- 18733865
TI  - Banquet Tickets.

PMID- 18733866
TI  - Another Example.

PMID- 18733867
TI  - The Same Breath.

PMID- 18733868
TI  - County Societies.

PMID- 18733869
TI  - Keep Up the Fees.

PMID- 18733870
TI  - Scheme Beautiful.

PMID- 18733871
TI  - To Country Secretaries.

PMID- 18733872
TI  - Amusing Situation.

PMID- 18733873
TI  - Astonishing Statements.

PMID- 18733874
TI  - Too Bad.

PMID- 18733875
TI  - An Inviting Opportunity.

PMID- 18733876
TI  - Indications for and Description of Mastoid Operation.

PMID- 18733877
TI  - Medical Licensure.

PMID- 18733878
TI  - Recognition of Affections of Upper Air Passages in School Children.

PMID- 18733880
TI  - Diet and Hydrotherapy in Treatment of Rheumatism and Gout.

PMID- 18733879
TI  - Etiology of Embolism.

PMID- 18733881
TI  - Proprietary Medicines: Some General Considerations.

PMID- 18733882
TI  - Case of Double Senile Cataract With Spontaneous Posterior Displacement.

PMID- 18733883
TI  - Nostrum from Viewpoint of the Pharmacist.

PMID- 18733885
TI  - Not Members Proprietary Association.

PMID- 18733884
TI  - County Societies.

PMID- 18733886
TI  - Los Angeles Medical Library.

PMID- 18733888
TI  - Destroyed Certificates.

PMID- 18733887
TI  - Pleasant Message from Nevada.

PMID- 18733889
TI  - Ungrateful San Francisco.

PMID- 18733890
TI  - Fire Risks.

PMID- 18733891
TI  - Merely a Specialty.

PMID- 18733892
TI  - Remember the Reason.

PMID- 18733894
TI  - Viavi Remedies.

PMID- 18733893
TI  - Tuberculosis Department.

PMID- 18733896
TI  - Occult Hemorrhages in Typhoid.

PMID- 18733895
TI  - German Hospital.

PMID- 18733898
TI  - Annoying Carelessness.

PMID- 18733897
TI  - Policy Holders.

PMID- 18733899
TI  - Gastroenteric Autointoxication.

PMID- 18733900
TI  - Pain.

PMID- 18733901
TI  - Sciatica and Diseases of the Posterior Urethra and Adnexa.

PMID- 18733902
TI  - Choice of Anesthesia.

PMID- 18733903
TI  - Local Anesthesia.

PMID- 18733905
TI  - Mississippi Valley Medical Association.

PMID- 18733904
TI  - Conservative Treatment of Hip Disease.

PMID- 18733906
TI  - Santa Clara County.

PMID- 18733907
TI  - California Public Health Association.

PMID- 18733908
TI  - Standing of Insurance Companies.

PMID- 18733909
TI  - German Hospital.

PMID- 18733910
TI  - Insurance Fees from the Policy Holders' Standpoint.

PMID- 18733911
TI  - San Joaquin Valley Medical Association.

PMID- 18733912
TI  - The Sins of Physicians.

PMID- 18733913
TI  - State Society.

PMID- 18733914
TI  - Lay Press Medicine.

PMID- 18733915
TI  - And Again.

PMID- 18733916
TI  - Another of Our Sins.

PMID- 18733918
TI  - Those Fees Once More.

PMID- 18733917
TI  - Proprietary Prostitution.

PMID- 18733919
TI  - Another Journal.

PMID- 18733921
TI  - District Committees.

PMID- 18733920
TI  - Treatment of Chronic Urethritis.

PMID- 18733923
TI  - Compulsory Registration and Fumigation in Tuberculosis.

PMID- 18733922
TI  - Twenty-five Cases of Tuberculosis Treated With Tuberculin.

PMID- 18733924
TI  - Sanitation in San Francisco From April 18th to August 1st.

PMID- 18733925
TI  - Urology.

PMID- 18733926
TI  - Subordination of Medical Journals to Proprietary Interests.

PMID- 18733927
TI  - Hernia of the Bladder.

PMID- 18733928
TI  - Miscarriage and its Treatment.

PMID- 18733929
TI  - County Societies.

PMID- 18733931
TI  - SPREAD OF LEPROSY.

PMID- 18733930
TI  - Femoral Herniotormy.

PMID- 18733932
TI  - Fraudulent Agent.

PMID- 18733933
TI  - More About the Cancer Trouble.

PMID- 18733934
TI  - Our Wicked San Francisco.

PMID- 18733935
TI  - William Wood & Co.

PMID- 18733937
TI  - Texas on Insurance.

PMID- 18733936
TI  - Is It Hard?

PMID- 18733939
TI  - Bad Books and Good.

PMID- 18733938
TI  - A Single Illustration.

PMID- 18733940
TI  - San Francisco Physicians.

PMID- 18733941
TI  - Available Locations.

PMID- 18733943
TI  - The Medical Record: An Enemy of the American Medical Association: From the
      Journal A. M. A., Sept. 15, 1906.

PMID- 18733942
TI  - Reprinted Articles.

PMID- 18733944
TI  - Spasmodic Torticollis.

PMID- 18733945
TI  - Spiral Organisms in Relation to Syphilis.

PMID- 18733946
TI  - Technic and Staining of Treponema Pallidum.

PMID- 18733947
TI  - Subnormal Accommodation As a Manifestation of Hysteria.

PMID- 18733948
TI  - Notes on Hydrocyanic Acid Poisoning.

PMID- 18733949
TI  - Surgical Anesthesia by Hydrobromate of Hyascine and Morphine.

PMID- 18733950
TI  - An Application of Treatment by Induction of Hyperemia to Smallpox.

PMID- 18733953
TI  - BENIGN CYSTIC EPITHELIOMA.

PMID- 18733951
TI  - County Societies.

PMID- 18733952
TI  - OAKLAND COLLEGE STUDENTS.

PMID- 18733954
TI  - HEMORRHAGE IN THE NEWBORN.

PMID- 18733955
TI  - Good Advice.

PMID- 18733957
TI  - Are We Doing All We Should?

PMID- 18733956
TI  - Four Years of Life.

PMID- 18733959
TI  - Politics and Asylums.

PMID- 18733958
TI  - Some of Our Duties.

PMID- 18733960
TI  - Duty of Organization.

PMID- 18733961
TI  - Organization and Education.

PMID- 18733962
TI  - Board of Examiners.

PMID- 18733964
TI  - ASSOCIATION OF AMERICAN MEDICAL COLLEGES.

PMID- 18733963
TI  - Work of the Board of Medical Examiners.

PMID- 18733965
TI  - ASSOCIATION OF AMERICAN MEDICAL COLLEGES.

PMID- 18733966
TI  - Thorough Organization the Present Need of the Medical Profession.

PMID- 18733967
TI  - Proprietary Medicines.

PMID- 18733968
TI  - General Enteroptosis.

PMID- 18733969
TI  - Spasmodic Torticollis (Concluded).

PMID- 18733970
TI  - Case of Pleural and Pericardial Effusion.

PMID- 18733972
TI  - Medical Societies.

PMID- 18733971
TI  - Some Aspects of Latter Day Irregularism.

PMID- 18733974
TI  - Alpha Omega Alpha.

PMID- 18733973
TI  - Sarcoma; Ten Feet of Intestine Removed.

PMID- 18733975
TI  - Suprapubic Prostatic Eneucleation.

PMID- 18733976
TI  - The Medical Practice Act.

PMID- 18733977
TI  - The Gerino Decision.

PMID- 18733978
TI  - Tuberculosis Sanatorium.

PMID- 18733979
TI  - American Medicine.

PMID- 18733980
TI  - Other Plans.

PMID- 18733981
TI  - Irregularities in Medical Schools and the Necessity for the Investigation of
      Credentials.

PMID- 18733982
TI  - Study of Sexuality.

PMID- 18733983
TI  - The Pronated Foot and Its Clinical Significance.

PMID- 18733984
TI  - Diet in Disease.

PMID- 18733985
TI  - Wilful Deception in a Case of Hysteria.

PMID- 18733986
TI  - Report of the 17th and 18th Cases of Coccidioidal Granuloma.

PMID- 18733988
TI  - COUNTY SOCIETIES.

PMID- 18733987
TI  - Proprietary Medicines and Their Abuses.

PMID- 18733989
TI  - PROFESSOR GEORGE BLUMER.

PMID- 18733990
TI  - A MEDICAL LIBRARY FOR SAN FRANCISCO.

PMID- 18733992
TI  - Railroads and Mail.

PMID- 18733991
TI  - GREAT AMERICAN FRAUD.

PMID- 18733993
TI  - Where is the Cure?

PMID- 18733995
TI  - Banti's Disease.

PMID- 18733994
TI  - The Physician's Responsibility for the Nostrum Evil.

PMID- 18733996
TI  - PROSTATECTOMY.

PMID- 18733997
TI  - GANGOSA.

PMID- 18733999
TI  - IDENTIFICATION BY FINGER PRINTS.

PMID- 18733998
TI  - AN IDEAL LIGATURE OR SUTURE.

PMID- 18734000
TI  - COUNTY SOCIETIES.

PMID- 18734001
TI  - The New York State Journal.

PMID- 18734002
TI  - And it is Virtuous!

PMID- 18734003
TI  - Fifth Volume.

PMID- 18734004
TI  - We Are Gullible.

PMID- 18734006
TI  - The Diagnosis of Some Lung Conditions Requiring Surgical Interference.

PMID- 18734005
TI  - A Combination of Syphilis and Epithelioma of the Tongue.

PMID- 18734008
TI  - Needless Anxiety.

PMID- 18734007
TI  - The Social Evil; Its Cost and Control.

PMID- 18734009
TI  - Osteopathic Physicians.

PMID- 18734010
TI  - Our Journals and the Council.

PMID- 18734012
TI  - Insurance Situation.

PMID- 18734011
TI  - Another Phase.

PMID- 18734013
TI  - Public Health Legislation.

PMID- 18734014
TI  - Is It Right?

PMID- 18734015
TI  - Some Important and Practical Points in Medicine.

PMID- 18734017
TI  - Operations on the Thyroid Gland.

PMID- 18734016
TI  - Address of the Retiring President, Dr. J. Lambert Asay, Santa Clara Co. Med. Soc.

PMID- 18734019
TI  - High Order of Medical Intelligence.

PMID- 18734018
TI  - Pres. Annual Address. Los Angeles Co. Med. Ass'n, Dec., 1906.

PMID- 18734020
TI  - Physicians Relief Committee.

PMID- 18734021
TI  - Our Relative Position.

PMID- 18734022
TI  - RESIGNED FROM COLLEGE OF PHYSICIANS AND SURGEONS.

PMID- 18734024
TI  - COLONIES FOR EPILEPTICS.

PMID- 18734023
TI  - COUNTY SOCIETIES.

PMID- 18734025
TI  - PURIFICATION OF SEWAGE.

PMID- 18734026
TI  - SOMNOS.

PMID- 18734028
TI  - REPORT OF THE COUNCIL ON PHARMACY AND CHEMISTRY.

PMID- 18734027
TI  - THE BACTERIA IN SCARLATINAL AND NORMAL THROATS.

PMID- 18734029
TI  - Small Fees.

PMID- 18734030
TI  - Society Work.

PMID- 18734031
TI  - State Society.

PMID- 18734032
TI  - Educational Campaign.

PMID- 18734033
TI  - Possible Strength.

PMID- 18734034
TI  - Excellent Agreement.

PMID- 18734035
TI  - Remarks on the Present Status of Intranasal Surgery.

PMID- 18734036
TI  - Support the Association.

PMID- 18734037
TI  - Report of a Case of Acute Pancreatitis.

PMID- 18734038
TI  - Diagnosis and Treatment of Ectopic Pregnancy.

PMID- 18734039
TI  - Clinical Note.

PMID- 18734040
TI  - European Clinics.

PMID- 18734041
TI  - Laboratory Methods of Diagnosis in Typhoid Fever.

PMID- 18734042
TI  - Treatment of a Few Diseases of the Rectum by the General Practitioner.

PMID- 18734043
TI  - Report of Focal-Operations in Hip-Joint Tuberculosis-A Discussion Finished.

PMID- 18734044
TI  - DEMONSTRATION OF A PATIENT SHOWING THE EFFECT OF THE X-RAY ON THE EPITHELIAL
      STRUCTURES OF THE SKIN.

PMID- 18734045
TI  - THE TREATMENT OF PYELITIS AND URETERITIS BY URETHRAL CATHETERIZATION AND LAVAGE.

PMID- 18734046
TI  - COUNTY SOCIETIES.

PMID- 18734047
TI  - AN HONOR TO A CALIFORNIA SURGEON.

PMID- 18734048
TI  - DR. GEORGE WASHINGTON FULLER.

PMID- 18734049
TI  - DR. GEORGE H. THOMA, OF NEVADA.

PMID- 18734051
TI  - We Aid Quackery.

PMID- 18734050
TI  - A BIOGRAPHICAL SKETCH OF THE LIFE OF DR. WEMPLE, SR.

PMID- 18734052
TI  - Opsonic Theory.

PMID- 18734054
TI  - Protect the Helpless.

PMID- 18734053
TI  - Viavi Treatment.

PMID- 18734055
TI  - The Physician and the Nostrum.

PMID- 18734056
TI  - Words on Opsonins.

PMID- 18734058
TI  - Discussion of Papers.

PMID- 18734057
TI  - Opsonic Technic.

PMID- 18734059
TI  - The Nauheim Treatment of Acute and Chronic Heart Failure.

PMID- 18734060
TI  - ALCOHOL: THE EFFECT OF ITS USE AND ABUSE.

PMID- 18734061
TI  - THE BARLOW MEDICAL LIBRARY OF LOS ANGELES.

PMID- 18734062
TI  - COUNTY SOCIETIES.

PMID- 18734063
TI  - ARMY MEDICAL CORPS EXAMINATION.

PMID- 18734065
TI  - MEDICAL BIOGRAPHIES.

PMID- 18734064
TI  - NO LANE LECTURES IN 1907.

PMID- 18734066
TI  - NEW CATALOGUE.

PMID- 18734067
TI  - Insurance Examinations.

PMID- 18734068
TI  - Robert Fleming Rooney, M.D.

PMID- 18734069
TI  - Annual Address of the President.

PMID- 18734070
TI  - Report of Council.

PMID- 18734071
TI  - Report of Secretary and Editor.

PMID- 18734072
TI  - Alcohol, the Effects of Its Use and Abuse.

PMID- 18734073
TI  - Concerning Genu Valgum Adolescentium.

PMID- 18734074
TI  - A REPORT OF THE FIRST TWO HUNDRED CONFINEMENTS AT THE SAN FRANCISCO MATERNITY.

PMID- 18734075
TI  - A CASE OF POISONING BY SMALL DOSES OF ATROPIN.

PMID- 18734076
TI  - CYCLODIALYSIS FOR CHRONIC GLAUCOMA.

PMID- 18734077
TI  - PROPRIETARY PREPARATIONS APPROVED BY COUNCIL ON PHARMACY AND CHEMISTRY.

PMID- 18734078
TI  - COUNTY SOCIETIES.

PMID- 18734080
TI  - NEUROGRAPHS: A Series of Neurological Studies, Cases and Notes.

PMID- 18734079
TI  - REPORT OF COMMITTEE ON INSURANCE FEES.

PMID- 18734082
TI  - Our New Rulers.

PMID- 18734081
TI  - A. M. A. Meeting.

PMID- 18734083
TI  - Good Work.

PMID- 18734084
TI  - Our Free Free Press.

PMID- 18734085
TI  - What Does It Mean?

PMID- 18734086
TI  - Rather Funny.

PMID- 18734087
TI  - Educate the Public.

PMID- 18734089
TI  - Doctor Davis.

PMID- 18734088
TI  - Worked Again?

PMID- 18734090
TI  - Numerous Attacks.

PMID- 18734091
TI  - This Manola.

PMID- 18734092
TI  - Frauds Exposed.

PMID- 18734093
TI  - Exposing the Fakes.

PMID- 18734095
TI  - Thought Stimulus.

PMID- 18734094
TI  - Antikamnia the Fake.

PMID- 18734096
TI  - Report of the Board of Medical Examiners.

PMID- 18734097
TI  - Specific Therapy in Tuberculosis.

PMID- 18734098
TI  - Earthquake Shock Considered as an Etilogical Factor in the Production of Mental
      and Nervous Diseases.

PMID- 18734099
TI  - Analysis of the Stomach Contents.

PMID- 18734100
TI  - Pure Milk Question of California Cities.

PMID- 18734101
TI  - Hip-Joint Disease.

PMID- 18734102
TI  - Two Anomalies of the Sigmoid Colon Resembling Diverticula.

PMID- 18734103
TI  - THE TREATMENT OF CERTAIN PHASES OF NEURASTHENIA.

PMID- 18734105
TI  - CALIFORNIA PURE FOOD COMMISSION NOTES.

PMID- 18734104
TI  - INFANTILE PARALYSIS: The Role of Physician and Specialist in its Treatment.

PMID- 18734106
TI  - COUNTY SOCIETIES.

PMID- 18734107
TI  - DEATH OF MRS. W. B. HARRINGTON.

PMID- 18734108
TI  - UNIVERSITY OF CALIFORNIA HOSPITAL.

PMID- 18734109
TI  - NEW BOARD OF EXAMINERS ORGANIZED.

PMID- 18734110
TI  - Pure Food Commission.

PMID- 18734111
TI  - A. M. A. Meeting.

PMID- 18734112
TI  - A Correction.

PMID- 18734114
TI  - A. M. A. Officers.

PMID- 18734113
TI  - Hall of Exhibits.

PMID- 18734115
TI  - Barred-Out Journals.

PMID- 18734116
TI  - Our Own Pages.

PMID- 18734117
TI  - State Society Secretaries.

PMID- 18734118
TI  - Shall It Be a Boycott?

PMID- 18734119
TI  - Ischemic Paralysis and Contracture.

PMID- 18734121
TI  - Aneurism of the Left Ventricle With Report of Case.

PMID- 18734120
TI  - Amplitude of Accommodation at Different Periods of Life.

PMID- 18734122
TI  - Dermoids of the Scalp.

PMID- 18734123
TI  - Gonorrheal Conjunctivitis: Clinical Course and Treatment.

PMID- 18734124
TI  - Differential Diagnosis of Organic from Functional Dyspepsia.

PMID- 18734125
TI  - EFFECT OF CHEMICALS ON THE HEART NERVES.

PMID- 18734126
TI  - THROAT INFECTIONS OF CHILDHOOD.

PMID- 18734127
TI  - PROPRIETARY PREPARATIONS APPROVED BY THE COUNCIL ON PHARMACY AND CHEMISTRY.

PMID- 18734128
TI  - OPSONIC INDEX TECHNIC IMPROVED.

PMID- 18734129
TI  - RUPTURE OF THE POSTERIOR MENINGEAL ARTERY WITHOUT FRACTURE AT THE POINT OF
      INJURY.

PMID- 18734131
TI  - HOUSE OF DELEGATES, AMERICAN MEDICAL ASSOCIATION.

PMID- 18734130
TI  - TUBERCULAR SYPHILIDE.

PMID- 18734132
TI  - COUNTY SOCIETIES.

PMID- 18734133
TI  - Important Ordinance.

PMID- 18734134
TI  - Please Forgive.

PMID- 18734135
TI  - Take a Vacation.

PMID- 18734136
TI  - Viavi Reprints.

PMID- 18734137
TI  - Supreme Court and the Arwine Case.

PMID- 18734139
TI  - Some Settled and Unsettled Points in Dietetics.

PMID- 18734140
TI  - Intensity of Pulmonic Sound in Mitral Incompetence.

PMID- 18734141
TI  - Results of Roentgenization in Superficial Malignancies.

PMID- 18734142
TI  - The X-Ray as a Therapeutic Factor.

PMID- 18734143
TI  - ACNE VULGARIS AND ITS TREATMENT.

PMID- 18734144
TI  - THE CONTROL OF DIPHTHERIA IN A PUBLIC SCHOOL.

PMID- 18734145
TI  - SUGGESTIONS ON METHODS OF ATTACKING TYPHOID FEVER IN SAN FRANCISCO.

PMID- 18734146
TI  - THE MANAGEMENT OF PLACENTA PREVIA, WITH A REPORT OF SEVEN CASES.

PMID- 18734147
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18734148
TI  - PURE FOOD COMMISSION NOTES.

PMID- 18734149
TI  - Frightful Condition.

PMID- 18734150
TI  - Aid Our Friends.

PMID- 18734151
TI  - Pure Food Commission.

PMID- 18734153
TI  - Illegal Practitioners.

PMID- 18734152
TI  - Oregon Cleansed.

PMID- 18734155
TI  - The Way We Are "Done".

PMID- 18734154
TI  - We Are Winning.

PMID- 18734157
TI  - A Return to Therapeutics.

PMID- 18734156
TI  - Constructive Campaign.

PMID- 18734158
TI  - Theophyllin as a Diuretic.

PMID- 18734159
TI  - Grocco's Sign.

PMID- 18734160
TI  - The Physiology of Glycosuria.

PMID- 18734162
TI  - SAN FRANCISCO'S HEALTH DEPARTMENT: Report to the Supervisors by the Health
      Officer, Dr. Jas. T. Watkins.

PMID- 18734161
TI  - Concerning the Necessity of Watching the Heart in Diabetes.

PMID- 18734164
TI  - COUNTY SOCIETIES.

PMID- 18734163
TI  - REPORT OF THE COMMITTEE (OF THE BOARD OF MEDICAL EXAMINERS) ON PROSECUTION OF
      ILLEGAL PRACTITIONERS.

PMID- 18734165
TI  - HERZSTEIN LECTURES.

PMID- 18734166
TI  - A DISCUSSION ON PERINEAL TEARS.

PMID- 18734167
TI  - AN APPEAL TO THE AMERICAN MEDICAL PROFESSION.

PMID- 18734168
TI  - ROCKEFELLER INSTITUTE.

PMID- 18734169
TI  - PURE FOOD COMMISSION NOTES.

PMID- 18734171
TI  - Physicians and Nurses.

PMID- 18734170
TI  - Short Papers.

PMID- 18734172
TI  - General Sanitation.

PMID- 18734173
TI  - Direct Illustration.

PMID- 18734174
TI  - A Singular Inconsistency.

PMID- 18734175
TI  - How To Do It.

PMID- 18734176
TI  - Railroad Mail Graft.

PMID- 18734177
TI  - Truth? Nit!

PMID- 18734178
TI  - Infant Feeding.

PMID- 18734180
TI  - Surgical Treatment of Gastroptosis.

PMID- 18734179
TI  - A Simple Method of Computing, Approximately, Percentages of Proteid, Fat or
      Carbohydrate in Milk Mixtures, Based on Analysis of San Francisco Milk.

PMID- 18734181
TI  - A Report of Two Cases of Epidural Abscess of Otitic Origin.

PMID- 18734183
TI  - Statistics, Etiology and Pathology.

PMID- 18734182
TI  - Mechanical Treatment of Hip-Joint Disease.

PMID- 18734185
TI  - SURGERY OF DIABETICS.

PMID- 18734186
TI  - OTITIC MEDIA IN CHILDREN, A NEW PRACTICAL POINT IN DIAGNOSIS. BACTERIAL
      INVESTIGATIONS.

PMID- 18734184
TI  - THE PROGNOSIS OF DIABETES.

PMID- 18734187
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18734188
TI  - DR. HURLEY HEALTH OFFICER.

PMID- 18734190
TI  - WASHINGTON STATE MEDICAL LAW SUSTAINED.

PMID- 18734189
TI  - RESOLUTIONS ADOPTED BY THE SAN FRANCISCO COUNTY MED. SOCIETY.

PMID- 18734191
TI  - WASHINGTON STATE ASSOCIATION.

PMID- 18734192
TI  - COUNTY SOCIETIES.

PMID- 18734193
TI  - Apropos of Plague.

PMID- 18734194
TI  - Shall We Do It?

PMID- 18734195
TI  - Enforce the Law.

PMID- 18734196
TI  - Why Should We Help?

PMID- 18734197
TI  - Signs of the Times.

PMID- 18734198
TI  - Another Apology.

PMID- 18734200
TI  - Plague.

PMID- 18734199
TI  - Slumber or Work?

PMID- 18734201
TI  - Plague in San Francisco.

PMID- 18734202
TI  - Effects of Baths on Blood Pressure.

PMID- 18734203
TI  - Insects and Infection.

PMID- 18734204
TI  - Brain Symptoms of Typhoid Fever Simulating Those of Mastoiditis.

PMID- 18734205
TI  - Functional Kidney Diagnosis.

PMID- 18734206
TI  - Uterus Forceps.

PMID- 18734207
TI  - The Evolution of the Disease-Entity Called Manio-Depressive Insanity, and Its
      Main Features.

PMID- 18734208
TI  - THE UNDERLYING CAUSES OF RHEUMATISM.

PMID- 18734210
TI  - MEDICAL TESTIMONY.

PMID- 18734209
TI  - COUNTY SOCIETIES.

PMID- 18734211
TI  - AMERICAN MEDICAL EDITOR'S ASSOCIATION, OFFICE OF THE PRESIDENT.

PMID- 18734213
TI  - AMERICAN MEDICAL EDITOR'S ASSOCIATION, OFFICE OF THE PRESIDENT.

PMID- 18734214
TI  - AMERICAN MEDICAL EDITOR'S ASSOCIATION, OFFICE OF THE PRESIDENT.

PMID- 18734212
TI  - GLORIOUS DEFEAT.

PMID- 18734216
TI  - RESOLUTIONS PASSED BY THE LOS ANGELES COUNTY MEDICAL ASSOCIATION OCTOBER 4, 1907.

PMID- 18734215
TI  - AMERICAN MEDICAL EDITOR'S ASSOCIATION, OFFICE OF THE PRESIDENT.

PMID- 18734217
TI  - RESOLUTIONS BY THE AMERICAN PHARMACEUTICAL ASSOCIATION.

PMID- 18734218
TI  - PURE FOOD COMMISSION NOTES.

PMID- 18734219
TI  - REMARKS BY WILLIAM C. ALPERS AT THE LAST GENERAL SESSION OF THE AMERICAN
      PHARMACEUTICAL ASSOCIATION.

PMID- 18734221
TI  - What to Do.

PMID- 18734220
TI  - Bubonic Plague.

PMID- 18734223
TI  - How to do it.

PMID- 18734222
TI  - The Press.

PMID- 18734225
TI  - Encouraging Reports.

PMID- 18734224
TI  - State Society.

PMID- 18734226
TI  - Curious Argument.

PMID- 18734227
TI  - The Other.

PMID- 18734228
TI  - Splendid Support.

PMID- 18734229
TI  - Prophylaxis and Eradication of Plague.

PMID- 18734230
TI  - Manio-Depressive Insanity.

PMID- 18734231
TI  - Extra Genital Chancres.

PMID- 18734232
TI  - Tabes as it Presents Itself to the General Practitioner.

PMID- 18734234
TI  - Fallaciousness of Diagnosis of Enlarged Prostate.

PMID- 18734233
TI  - Surgical Treatment of Motor Anomalies of the Eye.

PMID- 18734235
TI  - Fatal Case of Pemphigus.

PMID- 18734236
TI  - Myocarditis.

PMID- 18734237
TI  - INJURIES OF UPPER END OF FEMUR IN ADOLESCENTS AND CHILDREN.

PMID- 18734238
TI  - CHRONIC FLATULENCE.

PMID- 18734239
TI  - HEALTH OF SCHOOL CHILDREN.

PMID- 18734240
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18734241
TI  - A TOY REFLECTION.

PMID- 18734242
TI  - POISONING BY ANTIKAMNIA.

PMID- 18734243
TI  - COUNTY SOCIETIES.

PMID- 18734244
TI  - A New Year.

PMID- 18734245
TI  - Sixth Volume.

PMID- 18734246
TI  - Dudley Tait.

PMID- 18734247
TI  - Amputation Below the Knee Joint.

PMID- 18734248
TI  - Replacing of Bone and Cartilage of the Septum After Its Submucous Resection.

PMID- 18734249
TI  - Report of Cases of Head Injury.

PMID- 18734251
TI  - Scientific Program.

PMID- 18734250
TI  - The Medicinal Treatment of Myocarditis.

PMID- 18734252
TI  - The Plague Situation.

PMID- 18734253
TI  - TREATMENT OF HIP-JOINT DISEASE.

PMID- 18734254
TI  - INDICATIONS OF CESARIAN SECTION.

PMID- 18734256
TI  - PRELIMINARY REPORT ON A NEW PLASTER COMPOUND FOR PERMANENT SURGICAL DRESSINGS.

PMID- 18734255
TI  - FILLING OF BONE CAVITIES.

PMID- 18734258
TI  - Fish or Children?

PMID- 18734257
TI  - Homeopathic Materia Medica.

PMID- 18734259
TI  - "H. M. C." Tablets.

PMID- 18734260
TI  - SOCIETY OF EYE, EAR, NOSE AND THROAT SURGEONS OF SAN FRANCISCO.

PMID- 18734262
TI  - COUNTY SOCIETIES.

PMID- 18734261
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18734263
TI  - The Rat and His Parasites; His Role in the Spread of Disease, With Special
      Reference to Bubonic Plague.

PMID- 18734264
TI  - An Old Friend.

PMID- 18734265
TI  - The Continuance of Plague in San Francisco.

PMID- 18734266
TI  - Is It To Laugh?

PMID- 18734267
TI  - State Society.

PMID- 18734268
TI  - Internal Medicine.

PMID- 18734269
TI  - And Other Journals.

PMID- 18734270
TI  - The Plague Situation.

PMID- 18734271
TI  - About Journals.

PMID- 18734272
TI  - Why Not?

PMID- 18734273
TI  - Indiana Journal.

PMID- 18734274
TI  - The Permanent Eradication of the Plague.

PMID- 18734275
TI  - Medical Expert Testimony: Presidential Address, Santa Clara County Medical
      Society, December 18, 1907.

PMID- 18734276
TI  - Acromegaly With Facial Hemihypertrophy.

PMID- 18734278
TI  - Report of a Successful Suturing of a Double Stab Wound of the Femoral Artery, and
      a Single Wound of the Femoral Vein.

PMID- 18734277
TI  - A Report of Eleven Cerebral Complications Due to Acute and Chronic Suppuration of
      the Middle Ear.

PMID- 18734279
TI  - Rheumatism in Children.

PMID- 18734280
TI  - A Few Notes on Clinics for Diseases of the Skin.

PMID- 18734281
TI  - SUBJECTIVE SYMPTOMS AND PAINFUL SENSATIONS IN HEART DISEASE.

PMID- 18734282
TI  - COOPER COLLEGE SCIENCE CLUB.

PMID- 18734283
TI  - SAN FRANCISCO COUNTY.

PMID- 18734284
TI  - NEW AND NON-OFFICIAL REMEDIES CONTINUED FROM JANUARY.

PMID- 18734285
TI  - TRAINING IN MEDICAL ORGANIZATION.

PMID- 18734286
TI  - CONTRACT PRACTICE.

PMID- 18734287
TI  - COUNTY SOCIETIES.

PMID- 18734288
TI  - H. M. C. TABLETS.

PMID- 18734289
TI  - DEATH OF DR. ARTHUR E. GRESHAM.

PMID- 18734290
TI  - Zittmann's Decoction.

PMID- 18734292
TI  - San Francisco County Society.

PMID- 18734291
TI  - Perforation in Typhoid Fever Successfully Treated by Operation.

PMID- 18734293
TI  - RED CROSS.

PMID- 18734294
TI  - Resolutions by the Los Angeles County Medical Association.

PMID- 18734295
TI  - CRITICISM FROM AN OSTEOPATH.

PMID- 18734297
TI  - THE ROCKEFELLER INSTITUTE FOR MEDICAL RESEARCH, NEW YORK: Announcement of
      Scholarships and Fellowships.

PMID- 18734296
TI  - ARMY MEDICAL CORPS EXAMINATIONS.

PMID- 18734298
TI  - SMITHSONIAN INSTITUTION.

PMID- 18734299
TI  - COUNTY SOCIETIES.

PMID- 18734300
TI  - PHILADELPHIA MEDICAL SCHOOLS AND THE U. S. PHARMACOPEIA.

PMID- 18734301
TI  - Small Pox.

PMID- 18734303
TI  - Osteopathic Opinions.

PMID- 18734302
TI  - State Society.

PMID- 18734304
TI  - Pure Milk.

PMID- 18734306
TI  - Business Bureau.

PMID- 18734305
TI  - One Board or Three?

PMID- 18734307
TI  - "H. M. C." Tablets.

PMID- 18734308
TI  - San Francisco and the Plague Situation.

PMID- 18734309
TI  - Business Methods.

PMID- 18734310
TI  - The Awakening of Public Interest in San Francisco.

PMID- 18734312
TI  - Observations on Spinal Analgesia.

PMID- 18734311
TI  - Gastroenterostomy.

PMID- 18734313
TI  - A Plea for Contract Surgeons.

PMID- 18734314
TI  - Crimes or Maladies?

PMID- 18734315
TI  - Cystoscopic Appearance in Some Cases of Seminal Vesiculitis.

PMID- 18734316
TI  - Smallpox.

PMID- 18734317
TI  - Address Unknown.

PMID- 18734319
TI  - Sanitation or Politics?

PMID- 18734318
TI  - A Good Program.

PMID- 18734320
TI  - Plague Facts.

PMID- 18734321
TI  - Gas Rates and Plague.

PMID- 18734323
TI  - Alkaloidal Finance.

PMID- 18734322
TI  - Will They Feel Shame?

PMID- 18734324
TI  - Profit-Sharing Exploitations.

PMID- 18734325
TI  - Plague.

PMID- 18734326
TI  - Some Points on the Symptoms and Localization of Intestinal Obstruction Due to
      Carcinomata.

PMID- 18734327
TI  - Treatment of Syphilis of the Ear.

PMID- 18734328
TI  - Evils of Lodge Practice System.

PMID- 18734329
TI  - Early Treatment of Cross Eyes.

PMID- 18734330
TI  - Killian and Guisez Clinics.

PMID- 18734331
TI  - Bronchoscopy.

PMID- 18734332
TI  - General Paresis.

PMID- 18734333
TI  - Some Notes on Posology.

PMID- 18734334
TI  - Indications for Operations of the Stomach.

PMID- 18734335
TI  - OUR LACK OF BUSINESS METHODS.

PMID- 18734336
TI  - PYELONEPHRITIS COMPLICATING PREGNANCY.

PMID- 18734337
TI  - THE EXPERIMENTAL FEEDING OF BORACIC ACID TO WHITE RATS.

PMID- 18734338
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18734339
TI  - SAN FRANCISCO COUNTY.

PMID- 18734340
TI  - COOPER COLLEGE SCIENCE CLUB.

PMID- 18734341
TI  - SMALLPOX.

PMID- 18734343
TI  - TO AMERICAN PHYSICIANS INTERESTED IN THE ALCOHOLIC PROBLEM.

PMID- 18734342
TI  - AMENDMENT TO CONSTITUTION: Second Publication.

PMID- 18734345
TI  - COUNTY SOCIETIES.

PMID- 18734344
TI  - LEHN AND FINK'S ADVERTISING METHODS.

PMID- 18734346
TI  - SMITHSONIAN INSTITUTION.-HODGKINS FUND PRIZE.

PMID- 18734347
TI  - Coronado Meeting.

PMID- 18734348
TI  - Straw Men.

PMID- 18734349
TI  - Pure Food.

PMID- 18734350
TI  - The A. M. A.

PMID- 18734351
TI  - New Officers.

PMID- 18734352
TI  - Society Reports.

PMID- 18734353
TI  - San Francisco Physicians.

PMID- 18734354
TI  - Smallpox in Schools.

PMID- 18734355
TI  - Alkaloidal Abbott.

PMID- 18734356
TI  - Address of President: Medical Society of the State of California.

PMID- 18734357
TI  - George H. Evans, M. D: President, 1907-08.

PMID- 18734358
TI  - Report of Council.

PMID- 18734359
TI  - Report of Secretary.

PMID- 18734360
TI  - Report of Pure Food Commission.

PMID- 18734361
TI  - Report of Committee on Medical Education.

PMID- 18734362
TI  - Report of Tuberculosis Committee.

PMID- 18734363
TI  - Report of President to House of Delegates.

PMID- 18734364
TI  - THE WEBER MURDERS. WAS ADOLPH WEBER INSANE?

PMID- 18734365
TI  - THE FALLACIOUSNESS OF SO-CALLED PATHAGNOMONIC SIGNS IN DIAGNOSTIC WORK.

PMID- 18734366
TI  - THE REACTION OF ANAPHYLAXIS.

PMID- 18734367
TI  - A NERVE SEDATIVE.

PMID- 18734368
TI  - DEVELOPMENT OF THE COUNTY MEDICAL SOCIETY. PRESIDENT'S ADRRESS, SANTA BARBARA
      COUNTY MEDICAL SOCIETY.

PMID- 18734369
TI  - NOTICE TO ALUMNI OF THE TULANE MEDICAL DEPARTMENT.

PMID- 18734370
TI  - COLLEGE REUNIONS.

PMID- 18734371
TI  - COUNTY SOCIETIES.

PMID- 18734372
TI  - NEW REMEDIES APPROVED.

PMID- 18734373
TI  - Are Medical Organization and the State Society Worth While?

PMID- 18734374
TI  - Medical Treatment of Goitre.

PMID- 18734375
TI  - Surgical Treatment of Goitre.

PMID- 18734376
TI  - Relation of the Thyroid to Mental Disease.

PMID- 18734377
TI  - Discussion on Thyroid Gland Symposium.

PMID- 18734378
TI  - Fallaciousness of So-called Pathognomic Signs.

PMID- 18734380
TI  - Dementia Precox.

PMID- 18734379
TI  - Weber Case.

PMID- 18734382
TI  - SMALLPOX.

PMID- 18734381
TI  - Fungus Coccidioides.

PMID- 18734383
TI  - SOME EXPERIENCES OF A HEALTH OFFICER.

PMID- 18734384
TI  - COMMON GASTRIC DISORDERS AMONG SCHOOL CHILDREN.

PMID- 18734385
TI  - PROGRESS OF PREVENTIVE MEDICINE.

PMID- 18734386
TI  - COOPER COLLEGE SCIENCE CLUB: The Diagnosis of Certain Forms of Appendicitis.

PMID- 18734387
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18734388
TI  - The New Officers.

PMID- 18734389
TI  - The A. M. A. Meeting.

PMID- 18734391
TI  - County Officers.

PMID- 18734390
TI  - A Valuable Department.

PMID- 18734392
TI  - State Journals.

PMID- 18734393
TI  - Article on Plague.

PMID- 18734394
TI  - A Simple Illustration.

PMID- 18734395
TI  - The New Register.

PMID- 18734396
TI  - Acute Otitis Media in Infancy and Childhood.

PMID- 18734397
TI  - New State Journals.

PMID- 18734398
TI  - Indications for the Mastoid Operation.

PMID- 18734399
TI  - Prophylaxis and Treatment of Acute Otitis Media.

PMID- 18734401
TI  - Plague.

PMID- 18734400
TI  - Pathology of Acute Otitis Media, etc., with report of cases.

PMID- 18734402
TI  - ARMY MEDICAL EXAMINATIONS, 1908.

PMID- 18734403
TI  - COUNTY SOCIETIES.

PMID- 18734404
TI  - DR. CHARLES S. PORTER NOT DEAD.

PMID- 18734405
TI  - Signs of the Times.

PMID- 18734406
TI  - Important Suggestion.

PMID- 18734407
TI  - Ophthalmo Reaction.

PMID- 18734409
TI  - The New Register.

PMID- 18734408
TI  - Another Decision.

PMID- 18734410
TI  - A New Departure.

PMID- 18734411
TI  - A Work of Value.

PMID- 18734413
TI  - Pernicious Practices.

PMID- 18734412
TI  - A New Home.

PMID- 18734415
TI  - Such a Business!

PMID- 18734414
TI  - Is There a Reason?

PMID- 18734416
TI  - Stimulants Used in Cooking.

PMID- 18734417
TI  - Removal of Tonsils Under Local Anesthesia.

PMID- 18734418
TI  - Peripheral Endarteritis.

PMID- 18734419
TI  - The Status Lymphaticus.

PMID- 18734420
TI  - The Overproduction of Doctors.

PMID- 18734421
TI  - Underlying Principles of Antiplague Measures.

PMID- 18734422
TI  - Obstetrical Reminiscences.

PMID- 18734423
TI  - Plague.

PMID- 18734424
TI  - Malcolm Morris Knighted.

PMID- 18734425
TI  - FUNGUS COCCIDIOIDES-THE CALIFORNIA DISEASE.

PMID- 18734426
TI  - INTERNATIONAL CONGRESS ON TUBERCULOSIS.

PMID- 18734427
TI  - FIFTH PAN-AMERICAN MEDICAL CONGRESS.

PMID- 18734428
TI  - UNIVERSITY OF CALIFORNIA, MEDICAL DEPARTMENT, ALUMNI ASSOCIATION.

PMID- 18734429
TI  - ALAMEDA COUNTY.

PMID- 18734430
TI  - COUNCIL ON PHARMACY AND CHEMISTRY.

PMID- 18734431
TI  - A Good Example.

PMID- 18734432
TI  - Our Vast Ignorance.

PMID- 18734433
TI  - We Want Newspapers.

PMID- 18734434
TI  - Old Saws.

PMID- 18734435
TI  - Official Drivel.

PMID- 18734436
TI  - Prize Essay.

PMID- 18734438
TI  - The Harm We Work.

PMID- 18734437
TI  - Varicella or Varioloid.

PMID- 18734439
TI  - Family Addition.

PMID- 18734440
TI  - Relation of Anticyclonic Weather to La Grippe and Pneumonia.

PMID- 18734441
TI  - Review of Recent Work on Tuberculosis.

PMID- 18734442
TI  - When Is Gonorrhea Cured?

PMID- 18734443
TI  - When Is Gonorrhea Cured?

PMID- 18734444
TI  - Seborrhea and Its Sequelae.

PMID- 18734446
TI  - Plague.

PMID- 18734445
TI  - Clinical Features of Influenza Since the Pandemic of 1889-1890.

PMID- 18734448
TI  - ALAMEDA COUNTY.

PMID- 18734447
TI  - A GLANCE OVER THE DEVELOPMENT OF THE TECHNIC OF MODERN GYNECOLOGICAL OPERATIONS.

PMID- 18734449
TI  - A CRITICISM OF VALUE (?).

PMID- 18734450
TI  - THE SAMUEL D. GROSS PRIZE-FIFTEEN HUNDRED DOLLARS.

PMID- 18734451
TI  - THE FIRE INSURANCE COMPANIES AND THE SAN FRANCISCO FIRE.

PMID- 18734452
TI  - TO THE MEMBERS OF THE MEDICAL SOCIETY OF THE STATE OF CALIFORNIA.

PMID- 18734453
TI  - REASONABLE REQUEST FROM A PHARMACIST.

PMID- 18734454
TI  - Supposed to Work.

PMID- 18734455
TI  - Time to Get Busy.

PMID- 18734456
TI  - Consider the Quack.

PMID- 18734457
TI  - More Work.

PMID- 18734458
TI  - What We Work For.

PMID- 18734459
TI  - Our Real Influence.

PMID- 18734460
TI  - Our Own Benefit.

PMID- 18734461
TI  - A Word of Explanation.

PMID- 18734462
TI  - Very Sad Commentary.

PMID- 18734463
TI  - What Are You Doing?

PMID- 18734464
TI  - What is a Practical Examination in Anatomy?

PMID- 18734466
TI  - Prognosis and Treatment of Tuberculous Laryngitis.

PMID- 18734465
TI  - Drug Habits.

PMID- 18734467
TI  - Treatment of Aneurism by Direct Gradual Arterial Closure: Report of a Second Case
      of Aneurism of the Abdominal Aorta Treated by that Method.

PMID- 18734469
TI  - The Legal Aspect of an Incision.

PMID- 18734468
TI  - American Medical School and Its Entrance Requirements.

PMID- 18734471
TI  - Pre-Retinal Hemorrhage.

PMID- 18734470
TI  - A Normal Labor.

PMID- 18734472
TI  - Bacteriology and Pathology of Plague: With the Demonstration of Gross and
      Microscopic Specimens.

PMID- 18734473
TI  - THE OPTHALMO-TUBERCULIN REACTION.

PMID- 18734474
TI  - THE HOUSING PROBLEM.

PMID- 18734475
TI  - BERI-BERI.

PMID- 18734476
TI  - SANTA CLARA COUNTY.

PMID- 18734477
TI  - ADDRESS OF DR. KREUTZMANN UPON THE OPENING OF THE NEW GERMAN HOSPITAL.

PMID- 18734478
TI  - PUBLIC HEALTH EXHIBIT.

PMID- 18734479
TI  - PROF. A. MARTIN'S VISIT TO SAN FRANCISCO.

PMID- 18734481
TI  - WORK OF THE CONGRESS.

PMID- 18734480
TI  - REMARKABLE GATHERING.

PMID- 18734482
TI  - IS IT DOLLARS?

PMID- 18734483
TI  - UTTERLY ABSURD.

PMID- 18734484
TI  - AINT IT AWFUL!

PMID- 18734485
TI  - WHAT A DIFFERENCE.

PMID- 18734486
TI  - NOTABLE MEETING.

PMID- 18734487
TI  - PLAGUE PANDEMIC.

PMID- 18734488
TI  - WHAT IS IT TO BE?

PMID- 18734489
TI  - Cancer of the Uterus. How may we Secure its Earlier Recognition?

PMID- 18734490
TI  - Indications for Mastoid Operation.

PMID- 18734492
TI  - Sanitary Supervision of Bakeries and Restaurants.

PMID- 18734491
TI  - The Pure Milk Problem.

PMID- 18734494
TI  - Syphilis as Seen by the Eye, Ear, Nose and Throat Specialist.

PMID- 18734493
TI  - Leutic Stigmata of Importance to the General Practitioner.

PMID- 18734495
TI  - Syphilis of Bones and Joints.

PMID- 18734496
TI  - The Early Recognition and Treatment of Squint.

PMID- 18734497
TI  - San Joaquin County on Nostrums.

PMID- 18734498
TI  - Beri-Beri.

PMID- 18734499
TI  - SAN FRANCISCO COUNTY.

PMID- 18734500
TI  - CONCERNING THE ABBOTT ALKALOIDAL COMPANY.

PMID- 18734502
TI  - PUBLIC HEALTH AND CONSERVATION.

PMID- 18734501
TI  - UNIVERSITY OF CALIFORNIA HOSPITAL.

PMID- 18734503
TI  - INFORMATION FOR MEDICAL STUDENTS: From the Board of Medical Examiners.

PMID- 18734504
TI  - PROFESSOR CHARLES MINER COOPER.

PMID- 18734505
TI  - DR. A. W. HEWLETT GOES TO ANN ARBOR.

PMID- 18734506
TI  - SEPTIC RESEARCH.

PMID- 18734507
TI  - BARRED FROM THE MAIL.

PMID- 18734508
TI  - DEATH OF MRS. WILLS.

PMID- 18734509
TI  - INSULTING TO US ALL.

PMID- 18734511
TI  - LESSONS TAUGHT.

PMID- 18734510
TI  - THE END OF THE YEAR.

PMID- 18734512
TI  - HOSPITAL ABUSES.

PMID- 18734513
TI  - GERMAN HOSPITAL.

PMID- 18734514
TI  - ELECTION RESULTS.

PMID- 18734515
TI  - A CURIOUS CONDITION.

PMID- 18734516
TI  - DIAGNOSIS OF SYPHILIS.

PMID- 18734517
TI  - THE RECENT CONGRESS.

PMID- 18734518
TI  - Hematuria, with Report of Cases.

PMID- 18734519
TI  - CAN THIS BE TRUE?

PMID- 18734520
TI  - Pentoses.

PMID- 18734521
TI  - Postoperative Treatment.

PMID- 18734522
TI  - Opsonic Index and Vaccine Therapy.

PMID- 18734524
TI  - Russell Sage Foundation Book.

PMID- 18734523
TI  - Cementworker's Itch.

PMID- 18734526
TI  - Pyelo-Lithotomy.

PMID- 18734525
TI  - Polyclinic Gathering.

PMID- 18734527
TI  - The German Hospital Question.

PMID- 18734529
TI  - PURE FOOD EXHIBIT OF THE STATE BOARD OF HEALTH.

PMID- 18734528
TI  - County Societies.

PMID- 18734530
TI  - TUBERCULOSIS DIRECTORY.

PMID- 18734531
TI  - CUT RATE COMPETITION.

PMID- 18734532
TI  - MISSISSIPPI VALLEY MEDICAL ASSOCIATION.

PMID- 18734533
TI  - COLORADO SOUVENIR BOOK ON TUBERCULOSIS.

PMID- 18734535
TI  - PUBLIC HEALTH AND MARINE-HOSPITAL SERVICE, EXAMINATION OF APPLICANTS.

PMID- 18734534
TI  - CALIFORNIA BULLETIN ON TUBERCULOSIS.

PMID- 18734537
TI  - FOUND, POCKET CASE OF INSTRUMENTS.

PMID- 18734536
TI  - FER-DON, THE FAKIR AND HIS TAPE WORMS.

PMID- 18734538
TI  - STATE SOCIETY COMMITTEES.

PMID- 18734539
TI  - OUR LAW.

PMID- 18734540
TI  - VOLUME SEVEN.

PMID- 18734542
TI  - Bier Treatment in Surgical Diseases.

PMID- 18734541
TI  - German Measles.

PMID- 18734543
TI  - Intestinal Paralysis: Pseudo-ileus. Dynamic ileus. Adynamic ileus.

PMID- 18734544
TI  - The Treatment of Croupous Pneumonia.

PMID- 18734546
TI  - THE GIST OF THE LAW.

PMID- 18734545
TI  - PLENTY OF CRITICISM.

PMID- 18734547
TI  - CONSTANT WARFARE.

PMID- 18734548
TI  - The Question of Operative Interference in Acute Appendicitis.

PMID- 18734549
TI  - Pacific Association of Railway Surgeons' Official Minutes.

PMID- 18734551
TI  - Eye, Ear, Nose and Throat Society.

PMID- 18734550
TI  - The Treatment of Traumatic Rupture of the Urethra.

PMID- 18734552
TI  - SANE VIEWS.

PMID- 18734553
TI  - RAILWAY SURGEONS.

PMID- 18734554
TI  - The Skin Reaction After the Use of Tuberculin Ointment.

PMID- 18734555
TI  - SMALL PLACES DO GREAT THINGS.

PMID- 18734556
TI  - DR. A. H. VOORHIES.

PMID- 18734557
TI  - BOARD OF EXAMINERS.

PMID- 18734558
TI  - CONCERNING THE REGISTRATION OF BIRTHS.

PMID- 18734559
TI  - JAMES CARROLL.

PMID- 18734560
TI  - SMALLPOX AND THE STATE BOARD OF HEALTH.

PMID- 18734562
TI  - SUPPORT THE MEDICAL LAW.

PMID- 18734561
TI  - DR. FRANK LEMUEL ADAMS.

PMID- 18734563
TI  - COUNTY SOCIETIES.

PMID- 18734564
TI  - "PHENALEIN" OR "PURGEN.".

PMID- 18734566
TI  - SOUTHERN CALIFORNIA MEDICAL SOCIETY.

PMID- 18734565
TI  - HERZSTEIN LECTURES.

PMID- 18734567
TI  - ANTI-TUBERCULOSIS WORK.

PMID- 18734568
TI  - The Rose Bradford Kidney.

PMID- 18734569
TI  - WHY NOT GOOD LAWS?

PMID- 18734570
TI  - PURE MILK.

PMID- 18734571
TI  - AND THEN TUBERCULOSIS.

PMID- 18734572
TI  - ABOUT THE COMMITTEES.

PMID- 18734573
TI  - AND OUR ASYLUMS.

PMID- 18734575
TI  - OUR FEES.

PMID- 18734574
TI  - ABOUT EDITORIALS.

PMID- 18734576
TI  - INSURANCE IMPERTINENCE.

PMID- 18734577
TI  - The Utilization of Social Waste Products.

PMID- 18734578
TI  - EMMANUEL "MOVEMENT.".

PMID- 18734579
TI  - What is a Practical Examination in Anatomy? (Second Paper).

PMID- 18734580
TI  - The Treatment of Tuberculosis with Intravenous Injections of Tuberculin and
      Atoxyl.

PMID- 18734581
TI  - The Itch.

PMID- 18734582
TI  - On True Intestinal Dyspepsia.

PMID- 18734583
TI  - Treatment of Malignant Growths by the High Frequency Spark.

PMID- 18734585
TI  - Primary Pneumococcus Peritonitis: With Report of a Case.

PMID- 18734584
TI  - Suicide and Alcohol.

PMID- 18734586
TI  - The Early Recognition of Pulmonary Tuberculosis.

PMID- 18734587
TI  - Direct Transfusion of Blood.

PMID- 18734588
TI  - Treatment of Pneumonia.

PMID- 18734590
TI  - GOOD WORK IN PASADENA.

PMID- 18734589
TI  - County Societies.

PMID- 18734591
TI  - TUBERCULOSIS IN THE LEGISLATURE.

PMID- 18734592
TI  - PROPOSED CONSOLIDATION.

PMID- 18734593
TI  - TUBERCULOSIS CLINIC IN SAN FRANCISCO.

PMID- 18734594
TI  - DISTINGUISHED VISITOR.

PMID- 18734595
TI  - TUBERCULOSIS SANATORIA.

PMID- 18734596
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18734598
TI  - The Influence of Climate Upon Tuberculosis; With Remarks on the Climate of
      Colfax, California.

PMID- 18734597
TI  - The Leukemias and Allied Diseases.

PMID- 18734599
TI  - WAXED SILK AS A SUTURE.

PMID- 18734600
TI  - SIMPLIFICATION OF THE TECHNIC OF THE SERUM DIAGNOSIS OF SYPHILIS.

PMID- 18734601
TI  - COUNTY SOCIETIES.

PMID- 18734603
TI  - EMMANUEL MOVEMENT.

PMID- 18734602
TI  - STATE SOCIETY PROGRAM.

PMID- 18734605
TI  - DOCTOR FOSTER.

PMID- 18734604
TI  - BILLS ON TUBERCULOSIS.

PMID- 18734606
TI  - ABOUT BILLS MEDICAL.

PMID- 18734607
TI  - Review of the Work Done in the Anatomical Department of Cooper Medical College.

PMID- 18734608
TI  - COUNCIL ON EDUCATION.

PMID- 18734609
TI  - COUNTY SECRETARIES.

PMID- 18734610
TI  - Tobacco Amblyopia (from cigars) in a Woman.

PMID- 18734612
TI  - The Faucial Tonsils Considered From a Medical and Surgical Standpoint.

PMID- 18734611
TI  - A Case of Pyloric Stenosis in the Newly Born.

PMID- 18734613
TI  - The Tests for Involvement of the Labyrinth in Suppurative Middle Ear Processes.

PMID- 18734614
TI  - ADJOURNED, THANK GOD.

PMID- 18734615
TI  - NOTABLE ADVANCE.

PMID- 18734616
TI  - GENIUS DEBAUCHED.

PMID- 18734617
TI  - WE STILL PROGRESS.

PMID- 18734618
TI  - DEMONSTRATIONS ON HEALTH.

PMID- 18734619
TI  - BENZOATE OF SODA.

PMID- 18734620
TI  - LENGTHENING HUMAN LIFE.

PMID- 18734621
TI  - WHY NOT?

PMID- 18734622
TI  - THE WISE DOCTOR?

PMID- 18734623
TI  - Arteriosclerosis.

PMID- 18734624
TI  - Value of the Moro Skin-Reaction as Compared with other Methods of Using
      Tuberculin for Diagnosis in Tuberculosis.

PMID- 18734625
TI  - Treatment of Burns.

PMID- 18734626
TI  - Decapsulation of Kidneys-Case Report.

PMID- 18734628
TI  - Tuberculins.

PMID- 18734627
TI  - Typhoid Fever.

PMID- 18734629
TI  - Fee Division.

PMID- 18734630
TI  - Medical Milk Commissions and the Importance of a Pure Milk Supply.

PMID- 18734631
TI  - Report of the Milk Commission of the San Francisco County Medical Society.

PMID- 18734632
TI  - Persistent Omphalomesenteric with Accessory Pancreas.

PMID- 18734633
TI  - Spinal Anesthesia-A Critical Review.

PMID- 18734634
TI  - A Case of Scrotal Galactocele.

PMID- 18734635
TI  - WARREN TRIENNIAL PRIZE: Massachusetts General Hospital.

PMID- 18734636
TI  - COUNTY SOCIETIES.

PMID- 18734638
TI  - SAN FRANCISCO BRANCH, H. K. MULFORD COMPANY.

PMID- 18734637
TI  - UNIVERSAL ESPERANTO ASSOCIATION FOR PHYSICIANS.

PMID- 18734639
TI  - GROUND SQUIRRELS.

PMID- 18734640
TI  - REMARKABLY HEALTHY.

PMID- 18734641
TI  - ITALIAN-AMERICAN MEDICAL SOCIETY FORMED.

PMID- 18734642
TI  - HEALTH PAMPHLETS.

PMID- 18734644
TI  - AMERICAN PHARMACEUTICAL ASSOCIATION.

PMID- 18734643
TI  - DEATH OF DR. BULL.

PMID- 18734645
TI  - ACTIVE SECRETARIES.

PMID- 18734646
TI  - CASE IN POINT.

PMID- 18734647
TI  - SAN JOSE MEETING.

PMID- 18734648
TI  - WHY THESE ASSAULTS?

PMID- 18734649
TI  - ANOTHER REASON.

PMID- 18734650
TI  - BILL 1331.

PMID- 18734651
TI  - ABOUT ANTI-VACCINATION.

PMID- 18734652
TI  - NOTABLE BANQUET.

PMID- 18734653
TI  - Report of President to the House of Delegates.

PMID- 18734654
TI  - Report of the Secretary.

PMID- 18734655
TI  - Report of the Council.

PMID- 18734656
TI  - Report of the Public Health Commission of the Medical Society of the State of
      California for the Year 1908-1909.

PMID- 18734657
TI  - Report of the Committee on Public Policy and Legislation.

PMID- 18734658
TI  - Annual Report of the Committee on Tuberculosis.

PMID- 18734659
TI  - Report of the Committee on Cancer.

PMID- 18734660
TI  - Committee on Venereal Diseases.

PMID- 18734661
TI  - Wesley W. Beckett, M. D., President, 1908-1909.

PMID- 18734662
TI  - Address of Wm. T. Barry, M. D., to the Santa Barbara County Medical Society upon
      retiring from the Chair, January 8, 1909.

PMID- 18734663
TI  - Intestinal Obstruction.

PMID- 18734664
TI  - SOME REMINISCENCES OF INDIAN PRACTICE.

PMID- 18734665
TI  - VACCINES.

PMID- 18734666
TI  - A CLINICAL LECTURE ON WEAK-FOOT.

PMID- 18734668
TI  - MAJOR EMERGENCY OPERATIONS WITH REFERENCE TO FRACTURE OF THE SKULL AND WOUNDS OF
      THE ABDOMEN.

PMID- 18734667
TI  - A REVIEW OF THE TREATMENT OF GONORRHEAL INFLAMMATIONS BY THE USE OF SERA AND
      VACCINES.

PMID- 18734669
TI  - PHYSICIANS' MUTUAL AID ASSOCIATION.

PMID- 18734670
TI  - HOME NURSING COURSE FOR WOMEN.

PMID- 18734672
TI  - UNIVERSITY COURSE IN HYGIENE.

PMID- 18734671
TI  - UROPHERIN-S.

PMID- 18734673
TI  - COUNTY SOCIETIES.

PMID- 18734674
TI  - The Relief of Dr. Carroll's Widow.

PMID- 18734675
TI  - TO MEMBERS OF THE TUBERCULOSIS ASSOCIATION.

PMID- 18734676
TI  - PURELY ABUSE.

PMID- 18734677
TI  - A NEW SHAME.

PMID- 18734679
TI  - MEDICAL DEFENSE.

PMID- 18734678
TI  - INSURANCE NERVE!

PMID- 18734681
TI  - ENCOURAGE THE NURSES.

PMID- 18734680
TI  - DIVISION OF FEES.

PMID- 18734682
TI  - CURIOUS CHANGES.

PMID- 18734683
TI  - BIND YOUR JOURNALS.

PMID- 18734684
TI  - PRESIDENT'S COMMISSION.

PMID- 18734685
TI  - Antisepsis and Asepsis in Surgery.

PMID- 18734686
TI  - Amebic Dysentery.

PMID- 18734687
TI  - Latent Tuberculosis: Its Symptoms, Treatment and Prognosis.

PMID- 18734688
TI  - A Dosimetric Method of Anesthesia by Inhalation.

PMID- 18734689
TI  - Osteo-Arthritis.

PMID- 18734691
TI  - The Differential Diagnosis of Tubular Meningitis.

PMID- 18734690
TI  - A Case of Adactylia Involving Both Hands and the Left Foot with Right Amelus.

PMID- 18734693
TI  - Tuberculosis of the Kidneys.

PMID- 18734692
TI  - A Case of Brain Tumor.

PMID- 18734694
TI  - Report of a Case of Somnambulism Relieved by Hypnotic Suggestion.

PMID- 18734695
TI  - Reminiscenses of Ten Years as Commissioner of Health in Chicago, and Suggestions
      for the Future.

PMID- 18734696
TI  - BACKACHE.

PMID- 18734697
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18734698
TI  - COUNTY SOCIETIES.

PMID- 18734699
TI  - CRIMINAL ABORTION.

PMID- 18734701
TI  - ARMY MEDICAL CORPS EXAMINATIONS.

PMID- 18734700
TI  - TO THE EDITOR.

PMID- 18734703
TI  - THE A. M. A MEETING.

PMID- 18734702
TI  - UNITED STATES PHARMACOPOEIAL CONVENTION: Official Announcement of the First
      Decennial Meeting.

PMID- 18734705
TI  - THE NEW OFFICERS.

PMID- 18734704
TI  - THE NEW TRUSTEES.

PMID- 18734706
TI  - Critical Notes on Melancholia and Other Manifestations of the Depression
      Psychosis.

PMID- 18734707
TI  - PLACE OF MEETING.

PMID- 18734708
TI  - GATHER ENERGY.

PMID- 18734709
TI  - TAKE A VACATION.

PMID- 18734710
TI  - Backache.

PMID- 18734711
TI  - Some Fallacies in the Weaning of Infants.

PMID- 18734712
TI  - Fat as a Disturbing Factor in Infant Feeding.

PMID- 18734713
TI  - Arthritis Deformans.

PMID- 18734714
TI  - Passive Motion.

PMID- 18734715
TI  - The Interrelations of Glands with Internal Secretion.

PMID- 18734717
TI  - Local Anesthesia.

PMID- 18734716
TI  - The Malaria Zone.

PMID- 18734718
TI  - Our State Board Examination.

PMID- 18734719
TI  - Cooper College Science Club.

PMID- 18734720
TI  - DEMONSTRATION OF A SPLEEN.

PMID- 18734722
TI  - POLYCLINIC GATHERING: March 10, 1909.

PMID- 18734721
TI  - PULMONARY TUBERCULOSIS AS AFFECTED BY CERTAIN OTHER DISEASES.

PMID- 18734723
TI  - Dr. J. A. McNaughton, Los Angeles.

PMID- 18734724
TI  - ERROR IN THE OFFICIAL MINUTES.

PMID- 18734725
TI  - AMERICAN PHARMACEUTICAL ASSOCIATION.

PMID- 18734726
TI  - CREDIT TO LIPPINCOTT.

PMID- 18734727
TI  - COUNTY SOCIETIES.

PMID- 18734728
TI  - WHAT TO DO.

PMID- 18734730
TI  - SUITS FOR MALPRACTICE.

PMID- 18734729
TI  - MEDICAL DEFENSE.

PMID- 18734731
TI  - SIMPLIFIED OSTEOPATHY.

PMID- 18734732
TI  - LICENSE RECIPROCITY.

PMID- 18734733
TI  - HOW IT IS DONE.

PMID- 18734735
TI  - SOME OPEN LOCATIONS.

PMID- 18734734
TI  - THE SAME PITFALL.

PMID- 18734736
TI  - SCHOOL HYGIENE.

PMID- 18734737
TI  - Psychotherapy.

PMID- 18734738
TI  - Trichinosis: With a Report of Four Cases.

PMID- 18734739
TI  - Case of Hypertrophic Pyloric Stenosis With Autopsy Findings.

PMID- 18734740
TI  - Chyluria with a Vesical Sinus.

PMID- 18734741
TI  - Therapeutics.

PMID- 18734742
TI  - Sanitary Supervision of Communicable Diseases by the Department of Public Health.

PMID- 18734743
TI  - Obstruction of the Common Duct in Chronic Cholecystitis Without Stone.

PMID- 18734744
TI  - Galactoxismus.

PMID- 18734745
TI  - PROFESSIONAL WORK AS IT CONNECTS WITH THE MEDICAL SOCIETY AND THE GENERAL PUBLIC.

PMID- 18734746
TI  - THE TOXEMIC FACTOR IN RHEUMATOID ARTHRITIS.

PMID- 18734747
TI  - REPORT OF A CASE OF TRANSIENT CYCLOPLEGIA DUE TO GLYCOSURIA.

PMID- 18734748
TI  - THE RELATION OF RAT LEPROSY TO HUMAN LEPROSY: With an Exhibit of Gross and
      Microscopic Specimens.

PMID- 18734749
TI  - SOCIETY REPORTS.

PMID- 18734750
TI  - A FEW KIND WORDS.

PMID- 18734751
TI  - PACIFIC ASSOCIATION OF RAILWAY SURGEONS.

PMID- 18734752
TI  - ALASKA-YUKON-PACIFIC EXPOSITION.

PMID- 18734753
TI  - MEDICAL FAKIRS.

PMID- 18734754
TI  - DRY HEAT IN GYNECOLOGY.

PMID- 18734755
TI  - THERAPY OF MENINGITIS.

PMID- 18734756
TI  - CARDIAC MASSAGE.

PMID- 18734757
TI  - Requisites for the Treatment of the Psycho-Neuroses: Psychopathological
      Ignorance, and the Misuse of Psychotherapy by the Novice.

PMID- 18734759
TI  - The Treatment of Mucomembranous Colitis from the Standpoint of Its Bacterial
      Origin.

PMID- 18734758
TI  - Chronic Colitis.

PMID- 18734760
TI  - A Phase of Unequal Inspiratory Murmur.

PMID- 18734761
TI  - Some Conservative Surgical Procedure for Protecting and Preserving Pelvic Organs.

PMID- 18734762
TI  - The Hygienic and Climatic Treatment of Arteriosclerosis.

PMID- 18734764
TI  - The Theory and the Value of Tuberculins.

PMID- 18734763
TI  - Genito-Urinary Tuberculosis.

PMID- 18734765
TI  - The Immediate Removal Treatment of Morphin Habituation.

PMID- 18734766
TI  - Cutaneous Anesthesia as a Symptom of Osteomyelitis: Report of a Case.

PMID- 18734767
TI  - Surgical Treatment of Trifacial Neuralgia.

PMID- 18734768
TI  - RHEUMATISM: Its Relation to Diseases of the Throat.

PMID- 18734769
TI  - SUTURE OF THE AORTA.

PMID- 18734770
TI  - REVERSE PERISTALSIS.

PMID- 18734772
TI  - SOCIETY REPORTS.

PMID- 18734771
TI  - MERCURY IN THE TREATMENT OF TUBERCULOSIS.

PMID- 18734773
TI  - DANGEROUS DRUGS IN HEADACHE MEDICINES.

PMID- 18734774
TI  - DEPARTMENT OF TROPICAL MEDICINE.

PMID- 18734775
TI  - A JUST COMPLAINT.

PMID- 18734776
TI  - PROGRESS IN CUBA.

PMID- 18734778
TI  - GROUND SQUIRRELS AND PLAGUE.

PMID- 18734777
TI  - A FINE BEQUEST.

PMID- 18734779
TI  - A VICTIM TO DUTY.

PMID- 18734780
TI  - DIABETES IN NEW YORK CITY.

PMID- 18734781
TI  - POST-OPERATIVE PULMONARY COMPLICATIONS.

PMID- 18734783
TI  - The Predisposing Cause of Chronic Suppurative Otitis Media.

PMID- 18734782
TI  - HYSTERICAL PAROXYSMAL OEDEMA.

PMID- 18734784
TI  - Cerebral Complications of Middle Ear Suppuration.

PMID- 18734785
TI  - Eye Symptoms in Intracranial Complications Following Middle Ear Suppuration.

PMID- 18734786
TI  - The Treatment of Chronic Suppuration of the Middle Ear.

PMID- 18734787
TI  - Indications for Operation in Chronic Purulent Otitis Media.

PMID- 18734788
TI  - The Different Operations for Chronic Suppuration of the Middle Ear.

PMID- 18734789
TI  - Momberg's Tubing Applied as a Tourniquet for Bloodless Surgery of the Pelvis.

PMID- 18734790
TI  - Final Report of a Bone Transference.

PMID- 18734791
TI  - VACCINES.

PMID- 18734793
TI  - CRITICAL REVIEW: Momburg's Method of Producing Ischemia of the Lower Limbs and
      Pelvis.

PMID- 18734794
TI  - MIXED INFECTIONS IN PULMONARY TUBERCULOSIS; THEIR VACCINE THERAPY.

PMID- 18734792
TI  - A Case of Combined Typhoid and Malarial Infection.

PMID- 18734795
TI  - SOCIETY REPORTS.

PMID- 18734796
TI  - Report of a Case of Fracture of the Sixth Spinal Vertebra. Treated by Suture of
      the Cord. Death on the Sixty-seventh Day.

PMID- 18734797
TI  - CONTRA COSTA COUNTY.

PMID- 18734798
TI  - THE STATE BOARD OF HEALTH.

PMID- 18734799
TI  - REGISTER DIRECTORY.

PMID- 18734800
TI  - EARLY DIAGNOSIS OF PERTUSSIS.

PMID- 18734801
TI  - EXPLANATION AND THANKS.

PMID- 18734802
TI  - TUBERCLE BACILLI IN BLOOD.

PMID- 18734803
TI  - THE EXTENT OF SQUIRREL PLAGUE.

PMID- 18734804
TI  - The Diagnosis and Treatment of Ureteral Calculus.

PMID- 18734805
TI  - Post-Operative Phlebitis.

PMID- 18734806
TI  - Headache-A Symptom and Its Significance.

PMID- 18734807
TI  - The Medical Side of Headache.

PMID- 18734808
TI  - The Eye as a Causative Factor in Chronic Headaches with Reference to the Ear,
      Nose and Throat.

PMID- 18734810
TI  - VISIBLE MOVEMENT OF BLOOD IN RETINAL VESSELS.

PMID- 18734809
TI  - A REPORT OF SEVERAL CASES OF NEPHRITIS WITH UNUSUAL FEATURES.

PMID- 18734811
TI  - SOCIETY REPORTS.

PMID- 18734813
TI  - PROGRAM COMMITTEE.

PMID- 18734812
TI  - APPEAL TO THE MEDICAL PROFESSION OF THE WEST AND SOUTH.

PMID- 18734814
TI  - DRUG COMBINATIONS WITH ACETANILID.

PMID- 18734815
TI  - THE END OF A VOLUME.

PMID- 18734817
TI  - DR. CESARE LOMBROSO.

PMID- 18734816
TI  - MEDICAL DEFENSE.

PMID- 18734819
TI  - TROPICAL DISEASE IN OAKLAND.

PMID- 18734818
TI  - ANIMAL EXPERIMENTATION.

PMID- 18734820
TI  - TROPICAL MEDICINE.

PMID- 18734821
TI  - PELLAGRA.

PMID- 18734822
TI  - CHOLERA IN RUSSIA.

PMID- 18734823
TI  - Acute and Post Operative Dilatation of Stomach.

PMID- 18734824
TI  - A Consideration of Some Points in the Treatment of Infants.

PMID- 18734825
TI  - The Treatment of Flat and Pronated Feet.

PMID- 18734826
TI  - Address of Dr. Henry Gibbons, Jr., at the Commencement Exercises, Medical
      Department, Leland Stanford, Jr., University.

PMID- 18734827
TI  - PRACTICAL POINTS IN THE DIAGNOSIS OF EVERYDAY SKIN DISEASES.

PMID- 18734828
TI  - Three Non-Tuberculous Joint Lesions.

PMID- 18734829
TI  - ROENTGENOGRAPHIC FINDINGS IN FRACTURES ABOUT THE ELBOW JOINT.

PMID- 18734831
TI  - SOCIETY REPORTS.

PMID- 18734830
TI  - RAILWAY HYGIENE.

PMID- 18734833
TI  - TO COUNTY SECRETARIES.

PMID- 18734832
TI  - NEW YEAR'S PROBLEMS.

PMID- 18734834
TI  - The Use of Nitrous Oxide and Oxygen to Maintain Anesthesia and Positive Pressure
      for Thoracic Surgery.

PMID- 18734835
TI  - Conservative Treatment of Tuberculosis of the Genito-Urinary Organs.

PMID- 18734836
TI  - The Necessity for an Active Campaign Against Veneral Diseases.

PMID- 18734837
TI  - Dr. H. H. Rusby on Impure Drugs. An Address Before the Physicians of Redlands,
      California.

PMID- 18734838
TI  - YOU CAN HELP US.

PMID- 18734839
TI  - RABIES IN SOUTHERN CALIFORNIA.

PMID- 18734840
TI  - EXPERIMENTS ON ANIMALS.

PMID- 18734842
TI  - Enucleation of the Tonsil in its Bearing on General Injections.

PMID- 18734841
TI  - HUMAN FECES AS A CUREALL.

PMID- 18734843
TI  - Report and Presentation of Specimens of a Case of Central Cavity Formation in the
      Spinal Cord due to Trauma Without Fracture or Dislocation of the Vertebral
      Column.

PMID- 18734845
TI  - SOCIETY REPORTS.

PMID- 18734844
TI  - Comments on Tropical Medicine.

PMID- 18734846
TI  - CHEMICAL TESTS FOR BLOOD.

PMID- 18734847
TI  - Tropical Medicine.

PMID- 18734848
TI  - United States Pharmacopoeial Convention.

PMID- 18734849
TI  - THE TREATMENT OF WOUNDS.

PMID- 18734850
TI  - Lambotte Method.

PMID- 18734852
TI  - DR. ARBERRY CONVICTED.

PMID- 18734851
TI  - The Problem Presented by the Tuberculous Railway Employee.

PMID- 18734853
TI  - ANNUAL MEETING.

PMID- 18734854
TI  - LIBEL SUIT.

PMID- 18734856
TI  - PROSECUTION OF QUACKS.

PMID- 18734855
TI  - ADVANCES IN THORACIC SURGERY.

PMID- 18734857
TI  - SANITARY NEEDS.

PMID- 18734858
TI  - TUBERCULOSIS ORDINANCE.

PMID- 18734859
TI  - OUTRAGEOUS TREATMENT.

PMID- 18734860
TI  - SCIENTIFIC WORK ON PLAGUE.

PMID- 18734861
TI  - The Use of Coli and Streptococcic Vaccine in Urinary Diseases.

PMID- 18734862
TI  - Carcinoma and the Cervical Lymphatic System.

PMID- 18734863
TI  - IMPORTANCE OF THE EYE, EAR, NOSE AND THROAT EXAMINATIONS IN THE RAILWAY SERVICE.

PMID- 18734864
TI  - Amebiasis.

PMID- 18734865
TI  - Cesarean Section With Report of Nine Cases.

PMID- 18734866
TI  - Gunshot Wound of the Heart With Recovery.

PMID- 18734867
TI  - Some Phases in the Handling of Tuberculosis Patients.

PMID- 18734868
TI  - Observations on Brain Surgery.

PMID- 18734869
TI  - The Present Status of the Osmic Acid Treatment of Neuralgia.

PMID- 18734871
TI  - Comments on Tropical Medicine.

PMID- 18734870
TI  - A Critical Review. The Occurrence and Significance of the Boas-Oppler Bacillus in
      the Stools in Carcinoma of the Stomach.

PMID- 18734873
TI  - SOCIETY REPORTS.

PMID- 18734872
TI  - Dermatitis Factitia in a Patient With Pruritus Generalis. A Case Report.

PMID- 18734874
TI  - Dr. John Harvey Davisson.

PMID- 18734875
TI  - School Hygiene.

PMID- 18734877
TI  - Found Dead.

PMID- 18734876
TI  - Army Medical Corps Examinations at Washington, Chicago and San Francisco.

PMID- 18734878
TI  - Items From the Marine Hospital Service.

PMID- 18734879
TI  - Pellagra.

PMID- 18734880
TI  - Treatment of Pellagra.

PMID- 18734882
TI  - Congress on Hygiene.

PMID- 18734881
TI  - Plague in Ground Squirrels.

PMID- 18734883
TI  - Surgeon C. P. Wertenbaker.

PMID- 18734884
TI  - Pellagra in California.

PMID- 18734885
TI  - Comments on Tropical Medicine.

PMID- 18734886
TI  - Alkaptonuria.

PMID- 18734887
TI  - Society Reports.

PMID- 18734889
TI  - Dr. McCleave's Paper; a Curious Mistake.

PMID- 18734888
TI  - Physicians' Aid.

PMID- 18734890
TI  - W. B. Saunders Company, and not Appleton.

PMID- 18734891
TI  - RING TALK.

PMID- 18734892
TI  - THE A. M. A. DIRECTORY.

PMID- 18734893
TI  - ANNUAL MEETING.

PMID- 18734894
TI  - PUBLIC HEALTH COMMISSION.

PMID- 18734896
TI  - OPEN MEETINGS.

PMID- 18734895
TI  - PLAGUE NEWS.

PMID- 18734897
TI  - WHAT FOOLS THESE MORTALS BE.

PMID- 18734898
TI  - MEDICAL MACHINES.

PMID- 18734899
TI  - THE ORIGINAL PHARMACOPEIA.

PMID- 18734900
TI  - DELAYED RECOGNITION.

PMID- 18734901
TI  - The Uses of Bacterial Vaccines in Urinary Disease.

PMID- 18734902
TI  - The Treatment of Genito-Urinary Tuberculosis with Tuberculin.

PMID- 18734903
TI  - The Radical Treatment of Genito-Urinary Tuberculosis.

PMID- 18734905
TI  - President's Address at the Seventh Semi-Annual Meeting of the Central California
      Health Officers' Association, October, 1909.

PMID- 18734904
TI  - Surgical Shock.

PMID- 18734906
TI  - The Value of Cerebrospinal Fluid Examination in the Diagnosis of Chronic Nervous
      Disease.

PMID- 18734908
TI  - COMMITTEE ON ARRANGEMENTS.

PMID- 18734907
TI  - Congenital Dislocation of the Hip.

PMID- 18734909
TI  - SOMETHING FOR NOTHING.

PMID- 18734910
TI  - A FINE SCHEME.

PMID- 18734911
TI  - HOW IT HAS HAPPENED.

PMID- 18734912
TI  - THE POOR SUFFER.

PMID- 18734914
TI  - Comments on Tropical Medicine.

PMID- 18734913
TI  - MEDICINE'S LITERARY JUNGLE.

PMID- 18734915
TI  - LEST WE FORGET.

PMID- 18734917
TI  - Congenital Defects of the Muscles of the Face and Eyes. Infantiler Kernschwund of
      Moebius. Report of Three Cases.

PMID- 18734916
TI  - A New Vocation Dermatosis: Dermatitis Due to Dry Fulminate of Mercury.

PMID- 18734919
TI  - History of a Law Suit for Alleged Malpractice.

PMID- 18734918
TI  - Report of One Hundred Radical Mastoid Operations.

PMID- 18734920
TI  - Tuberculosis and the Modes of Infection.

PMID- 18734922
TI  - Labyrinthitis: Its Physiology, Methods of Diagnosis and Report of Two Cases.

PMID- 18734921
TI  - Selected Chapters from the Study of Speech Disturbances.

PMID- 18734923
TI  - The Relation of Law to Medicine.

PMID- 18734925
TI  - A TESTIMONIAL.

PMID- 18734924
TI  - A Case of Mastoiditis with Sinus Thrombosis.

PMID- 18734926
TI  - Bill No. 112. Ordinance No. 975 (New Series).

PMID- 18734927
TI  - Bill No. 1168. Ordinance No. 1040 (New Series).

PMID- 18734929
TI  - Society Reports.

PMID- 18734928
TI  - California Academy of Medicine: Chronic Uranium Nephritis in Animals.

PMID- 18734930
TI  - Dr. Hodghead not Connected with the P. and S.

PMID- 18734931
TI  - Cost of City Governments and Health Departments.

PMID- 18734932
TI  - New Journal.

PMID- 18734934
TI  - DEPARTMENT OF HEALTH.

PMID- 18734933
TI  - ANNUAL MEETING.

PMID- 18734935
TI  - THE WORST QUACKS.

PMID- 18734936
TI  - GOOD WORK.

PMID- 18734937
TI  - MORE ON THE SAME.

PMID- 18734938
TI  - Ether and Immunity.

PMID- 18734939
TI  - A Case of Leprosy in San Francisco Previously Undiscovered.

PMID- 18734940
TI  - History of a Lawsuit for Alleged Malpractice.

PMID- 18734941
TI  - Prosecution of Illegal Practitioners.

PMID- 18734943
TI  - Traumatic Injuries of the Head.

PMID- 18734942
TI  - A Case of Tumor of the Medulla Oblongata.

PMID- 18734944
TI  - Remarks Under Head of Geographical Distribution of Leprosy.

PMID- 18734945
TI  - The Psychoneurosis, a Review of the Present Status of Hysteria and Neurasthenia.

PMID- 18734946
TI  - The Normal Shape of the Stomach; Its Physical and Dietetic Therapy.

PMID- 18734948
TI  - To the Medical Profession.

PMID- 18734947
TI  - Society Reports.

PMID- 18734949
TI  - Army Medical Corps Examination.

PMID- 18734950
TI  - Honor to Dr. Colby Rucker.

PMID- 18734951
TI  - New and Non-Official Remedies.

PMID- 18734952
TI  - MEDICAL DEFENSE.

PMID- 18734953
TI  - HARMFUL PRACTICE.

PMID- 18734955
TI  - TUBERCULOSIS SUNDAY.

PMID- 18734954
TI  - TUBERCULOSIS CAMPAIGN.

PMID- 18734956
TI  - NASTY WORK.

PMID- 18734958
TI  - EASY MONEY.

PMID- 18734957
TI  - CORRESPONDING EDITORS.

PMID- 18734959
TI  - Dr. Jas. H. Parkinson, M. D., President, 1909-10.

PMID- 18734960
TI  - A Report of the President.

PMID- 18734961
TI  - Report of the Secretary.

PMID- 18734963
TI  - Eye, Ear, Nose and Throat Section of the State Society.

PMID- 18734962
TI  - Report of the Council.

PMID- 18734964
TI  - Statistics from Medical Schools in the State of California.

PMID- 18734965
TI  - Report of the Committee on Medical Defense.

PMID- 18734966
TI  - Report of the Editor.

PMID- 18734968
TI  - Auditor's Report.

PMID- 18734967
TI  - Report of the California State Board of Medical Examiners.

PMID- 18734969
TI  - Urticaria-With Special Reference to the Cause in the Papular Forms of Children.

PMID- 18734971
TI  - Officers of the Urological Association.

PMID- 18734970
TI  - Clinical Features of Endemic Grippe in Children in San Francisco and Vicinity.

PMID- 18734972
TI  - Department of Pharmacy and Chemistry.

PMID- 18734973
TI  - Society Reports.

PMID- 18734974
TI  - Public Health League.

PMID- 18734975
TI  - Dr. Von Hoffmann's Statement.

PMID- 18734976
TI  - MEDICAL DEFENSE.

PMID- 18734977
TI  - CANDOR WITH TUBERCULOSIS PATIENTS.

PMID- 18734978
TI  - WHOSE MONEY?

PMID- 18734979
TI  - MEDICAL FREEDOM.

PMID- 18734980
TI  - Symposium on Thoraic Surgery. Fortieth Annual Meeting of the Medical Society of
      the State of California, Sacramento, April 21, 1910: Surgery of the Lungs.

PMID- 18734981
TI  - PREVALENCE OF DISCONTENT.

PMID- 18734982
TI  - A. M. A. MEETING IN LOS ANGELES.

PMID- 18734983
TI  - Differential Pressure.

PMID- 18734984
TI  - Methods of Differential Pressure.

PMID- 18734985
TI  - The Future of Heart Surgery.

PMID- 18734986
TI  - Clinical Features of Hypophysis Disease.

PMID- 18734987
TI  - A Plea for a State Institution for the Treatment of Chronic Alcoholic and Drug
      Habitues.

PMID- 18734988
TI  - Prolonged Dilatation for Dysmenorrhea.

PMID- 18734989
TI  - The Ethical Versus the Commercial Side of Medical Practice-Which Will We Serve?

PMID- 18734990
TI  - Abdominal Injuries With Special Reference to Early Diagnosis and Treatment.

PMID- 18734991
TI  - Department of Pharmacy and Chemistry.

PMID- 18734992
TI  - The Revision of the U. S. Pharmacopeia.

PMID- 18734993
TI  - Society Reports.

PMID- 18734994
TI  - Notice. Medical Defense.

PMID- 18734995
TI  - Pessaries Wanted.

PMID- 18734996
TI  - Illness of Dr. King.

PMID- 18734997
TI  - ANOTHER CONVICTION.

PMID- 18734999
TI  - THE WASSERMAN TEST FOR SYPHILIS IN PRACTICE.

PMID- 18734998
TI  - ARBERRY AGAIN.

PMID- 18735000
TI  - THE VALUE OF DRUGS.

PMID- 18735001
TI  - THE ST. LOUIS MEETING OF THE A. M. A.

PMID- 18735002
TI  - EMPYRICISM VS. RATIONALISM IN SURGERY.

PMID- 18735003
TI  - The Essentials of Surgical Diagnosis with Reference to Fractures.

PMID- 18735004
TI  - Epidemic Meningitis in California and Its Treatment with Flexner's Anti
      Meningitis Serum.

PMID- 18735005
TI  - Treatment of Fractures of Humerus Through Musculo-Spiral Groove.

PMID- 18735006
TI  - A Case of Theocin Poisoning.

PMID- 18735007
TI  - Pain as a Symptom in Secondary Syphilis.

PMID- 18735008
TI  - Brief Notes on Skin Diseases in the Hawalian Territory-The Sun as a Modifying
      Factor.

PMID- 18735009
TI  - The Importance of Modification of the Sensibility in the Diagnosis of Disease in
      the Light of Recent Neurological Research.

PMID- 18735011
TI  - Report of a Case of Sick-Headache.

PMID- 18735010
TI  - Dr. Camillus Bush. Memorial Exercises Held by the California Academy of Medicine,
      June 28, 1910.

PMID- 18735012
TI  - Report of a Case of Intra Thoracic Tumor.

PMID- 18735013
TI  - Demonstration of Case of Fracture Treated by Operation.

PMID- 18735014
TI  - The Immobilization of Fractures.

PMID- 18735016
TI  - Society Reports.

PMID- 18735015
TI  - Medical Ethics in San Francisco.

PMID- 18735018
TI  - Davis Memorial Committee of the A. M. A.

PMID- 18735017
TI  - Pacific Association of Railway Surgeons.

PMID- 18735019
TI  - FLORENCE NIGHTINGALE.

PMID- 18735021
TI  - WHAT IS THE GAME?

PMID- 18735020
TI  - MEDICAL ILLUMINATION.

PMID- 18735023
TI  - PROFESSOR EHRLICH'S NEW REMEDY FOR SYPHILIS.

PMID- 18735022
TI  - CO-OPERATION IN WORK.

PMID- 18735024
TI  - STATUS OF OSTEOPATHY.

PMID- 18735025
TI  - Remarks of Oscar C. Mueller, Chairman of Committee on Amendment of Laws of the
      Los Angeles Bar Association, on "Medical Expert Testimony.".

PMID- 18735026
TI  - Medical Expert Testimony.

PMID- 18735027
TI  - Report of the Carnegie Foundation for the Advancement of Teaching in Medical
      Schools of California.

PMID- 18735028
TI  - The Carnegie Foundation Report.

PMID- 18735029
TI  - The Carnegie Report-A Comment.

PMID- 18735030
TI  - A Protest From Cooper Medical College: The Carnegie Foundation for the
      Advancement of Teaching, 576 Fifth Ave., New York, N. Y.

PMID- 18735031
TI  - The Problem of Pre-Medical Education.

PMID- 18735032
TI  - Some Notes on Nitrous Oxid and Oxygen for Prolonged Anesthesia and a Report of a
      Few Critical Cases.

PMID- 18735033
TI  - Frontal Sinus Suppuration.

PMID- 18735035
TI  - Comments on Tropical Medicine.

PMID- 18735036
TI  - Lane Medical Lectures.

PMID- 18735034
TI  - Two Cases of Tumor in the Fourth Ventricle and Cerebellum.

PMID- 18735037
TI  - Case Reports.

PMID- 18735038
TI  - A Case of Poisoning by Subnitrate of Bismuth.

PMID- 18735040
TI  - Department of Pharmacy and Chemistry.

PMID- 18735039
TI  - An Unusual Case of Strangulated Hernia.

PMID- 18735041
TI  - Concerning Osteopathy.

PMID- 18735042
TI  - Society Reports.

PMID- 18735043
TI  - Illegal Practitioners and Advertising Quacks.

PMID- 18735044
TI  - Queer Mistakes in Insurance Examination.

PMID- 18735045
TI  - Danger in the Sugar Bowl.

PMID- 18735046
TI  - Public Health Commission.

PMID- 18735047
TI  - Another Victim of Medical Work.

PMID- 18735049
TI  - THIS IS DISHEARTENING.

PMID- 18735048
TI  - State Board Bulletin.

PMID- 18735050
TI  - A WORD TO OUR ADVERTISERS.

PMID- 18735052
TI  - NOT ALL BLACK.

PMID- 18735051
TI  - ANOTHER CONVICTION.

PMID- 18735054
TI  - PERSONAL MENTION.

PMID- 18735053
TI  - DEPARTMENT OF HEALTH.

PMID- 18735056
TI  - EMPIRE COMPANY.

PMID- 18735055
TI  - RAILWAY SURGEONS.

PMID- 18735058
TI  - THE LANE LECTURES.

PMID- 18735057
TI  - Carnegie Foundation Report on Medical Education; a Reply to the Criticisms from
      Cooper Medical College.

PMID- 18735059
TI  - Treatment of Chronic Gastric Ulcer.

PMID- 18735061
TI  - Indications and Contraindications for the Use of Spinal Anesthesia.

PMID- 18735060
TI  - A Case of Twitching of the Orbicularis Palpebrarum Successfully Treated with
      Calcium Chlorid.

PMID- 18735062
TI  - Necessary Reforms Governing Medical Expert Testimony.

PMID- 18735063
TI  - Medical Expert Testimony.

PMID- 18735064
TI  - Correspondence.

PMID- 18735066
TI  - Correspondence.

PMID- 18735065
TI  - Bovine Tuberculin in the Treatment of Pulmonary Tuberculosis.

PMID- 18735068
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18735067
TI  - Scientific Review: Symptomology of Infantile Paralysis.

PMID- 18735069
TI  - U. S. PHARMACOPOEIAL CONVENTION 1910-1920.

PMID- 18735070
TI  - Society Reports.

PMID- 18735071
TI  - A Case of Tertiary Malaria Simulating General Septic Peritonitis.

PMID- 18735073
TI  - A Case of Depressed Fracture of Skull With Spontaneous Elevation of the
      Depression and Complete Recovery.

PMID- 18735072
TI  - Comments on Tropical Medicine.

PMID- 18735074
TI  - The Henry Phipps Institute for the Study, Prevention and Treatment of
      Tuberculosis.

PMID- 18735075
TI  - Anti-Meningitis Serum.

PMID- 18735076
TI  - Report of Public Health Committee.

PMID- 18735077
TI  - HONEST BUSINESS.

PMID- 18735078
TI  - SPASM OF VIRTUE!

PMID- 18735080
TI  - PONDS TAMPONS.

PMID- 18735079
TI  - TUBERCLE BACILLI IN SPUTUM.

PMID- 18735082
TI  - RELATION OF INTESTINES TO PULMONARY ANTHRACOSIS.

PMID- 18735081
TI  - PHYSICIANS' DEFENSE CO.

PMID- 18735083
TI  - BRUDZINSKI'S SIGNS OF MENINGITIS.

PMID- 18735085
TI  - Nephritis of Bacterial Origin.

PMID- 18735084
TI  - Experimental Nephritis.

PMID- 18735086
TI  - Hematuria; an Initial Symptom of Chronic Nephritis.

PMID- 18735087
TI  - The Dietetic Treatment of Nephritis.

PMID- 18735088
TI  - Pellagra; with Demonstration of a Case.

PMID- 18735089
TI  - History of Rabies in Southern California.

PMID- 18735090
TI  - The Demonstration of a Dissection Showing an Anomaly of the Arteries of the Leg,
      with an Interpretation.

PMID- 18735091
TI  - Ureterocystostomy.

PMID- 18735092
TI  - A Review of Some Points in Cerebral Physiology with Reference to their
      Application to Surgery of the Brain.

PMID- 18735093
TI  - To Refute a Sneer.

PMID- 18735094
TI  - The Certified Milk Fund.

PMID- 18735095
TI  - Resolutions Commending Dr. Rucker.

PMID- 18735097
TI  - THE NEXT LEGISLATURE.

PMID- 18735096
TI  - Disappeared.

PMID- 18735098
TI  - EIGHTH VOLUME.

PMID- 18735099
TI  - A MEDICAL CLEARING HOUSE.

PMID- 18735100
TI  - A WORD ON ADVERTISING.

PMID- 18735102
TI  - ETIOLOGICAL FACTORS IN APPENDICITIS.

PMID- 18735101
TI  - ACTION OF ATOXYL ON EYES.

PMID- 18735103
TI  - THE FUNCTIONS OF THE COUNTY MEDICAL SOCIETY.

PMID- 18735104
TI  - Symposium on the Tonsils: The Enucleation of the Tonsil From the Standpoint of
      the General Medical Man.

PMID- 18735105
TI  - President's Address: Tendon Transplantation.

PMID- 18735107
TI  - The Late Dr. G. L. Simmons, of Sacramento.

PMID- 18735106
TI  - Strangulated Hernia.

PMID- 18735108
TI  - Los Angeles County Medical Associations.

PMID- 18735109
TI  - THE STATUTE REGULATING THE PRACTICE OF MEDICINE IN CALIFORNIA IS A PROPER
      EXERCISE OF THE POLICE POWER.

PMID- 18735111
TI  - Society Reports.

PMID- 18735110
TI  - The Medical Law.

PMID- 18735112
TI  - Cooper College Science Club.

PMID- 18735113
TI  - California Academy.

PMID- 18735114
TI  - A Menace to the Public Welfare.

PMID- 18735116
TI  - Army Medical Corps Examination.

PMID- 18735115
TI  - Nostrums in a New Guise.

PMID- 18735118
TI  - THE NEW YEAR.

PMID- 18735117
TI  - GOOD REMEDIES.

PMID- 18735120
TI  - JUST LIES.

PMID- 18735119
TI  - DIRTY AND DANGEROUS.

PMID- 18735121
TI  - Insects and Medicine. A Lecture.

PMID- 18735122
TI  - Report of a Case of Epidemic Cerebro-Spinal Meningitis.

PMID- 18735123
TI  - Renal Tuberculosis.

PMID- 18735124
TI  - The Co-Operation of School Health Departments With Other Health Agencies.

PMID- 18735125
TI  - A Brief Account of Ludwig Pick's Work on Chorion Epithelioma.

PMID- 18735127
TI  - MEDICAL EXPERT TESTIMONY.

PMID- 18735126
TI  - MISSIONARY PHYSICIANS.

PMID- 18735128
TI  - DIVISION OF FEES.

PMID- 18735129
TI  - TOXIC CORD.

PMID- 18735130
TI  - VENEREAL DISEASES.

PMID- 18735131
TI  - A Study in Heart Tonics.

PMID- 18735132
TI  - Multiple Papillomata of the Urethra.

PMID- 18735133
TI  - Remarks on Impotentia Cocundi and Sexual Neurasthenia and Their Treatment.

PMID- 18735134
TI  - A Case of Filariasis Treated by the Wherry-McDill Method.

PMID- 18735136
TI  - Department of Pharmacy and Chemistry.

PMID- 18735135
TI  - A Case of Splenomegaly With Fatal Hematemesis.

PMID- 18735137
TI  - SCIENTIFIC PROGRAM.

PMID- 18735138
TI  - THE GASTRO-INTESTINAL TRACT AS AN ORGAN OF EXCRETION.

PMID- 18735139
TI  - THE A. M. A. MEETING.

PMID- 18735140
TI  - ATROPHY OF TONGUE AND SYPHILIS.

PMID- 18735141
TI  - Subcutaneous Injuries of the Abdominal Contents.

PMID- 18735142
TI  - Hospital Service for Railroad Construction Camps in the Pacific Northwest.

PMID- 18735143
TI  - Functional Periodicity in Women and Some of the Modifying Factors: Second Note.

PMID- 18735144
TI  - SOCIETY REPORTS.

PMID- 18735146
TI  - Academy of Medicine.

PMID- 18735145
TI  - Of Interest.

PMID- 18735148
TI  - Classification of Insanity as Adopted by the State Lunacy Commission in Force
      Since July 1, 1908.

PMID- 18735147
TI  - Cooper College Science Club.

PMID- 18735150
TI  - The Late Dr. George Goodfellow.

PMID- 18735149
TI  - California State Board of Health Announcement: Syphilis and Gonococcus Infections
      to Be Reportable.

PMID- 18735151
TI  - Resolution on Division of Fees.

PMID- 18735153
TI  - Serum Diagnosis of Syphilis.

PMID- 18735152
TI  - A Few Notes on the New Remedy for Syphilis, "Ehrlich, 606.".

PMID- 18735154
TI  - EDDYITE DOINGS.

PMID- 18735155
TI  - PUBLIC HEALTH.

PMID- 18735156
TI  - THE PRESENT LEGISLATURE.

PMID- 18735157
TI  - CURIOUS DELUSIONS.

PMID- 18735158
TI  - ADVERTISING ONCE MORE.

PMID- 18735159
TI  - PROGRESS IN THORACIC SURGERY.

PMID- 18735160
TI  - MEDICAL CHARITY.

PMID- 18735161
TI  - MISPLACED SYMPATHY.

PMID- 18735162
TI  - MARVELOUS BACTERIOLOGY.

PMID- 18735163
TI  - 50,000 DOLLARS.

PMID- 18735164
TI  - Hyperchlorhydria.

PMID- 18735166
TI  - Functional Periodicity in Women and Some of the Modifying Factors.

PMID- 18735165
TI  - The Value of Rectal Examinations.

PMID- 18735167
TI  - The Relation of Gastric Hemorrhage to Chronic Appendicitis.

PMID- 18735168
TI  - A Method for the Determination of the Pus in Diseases of the Accessory Cavities
      of the Nose.

PMID- 18735169
TI  - Unusual Manifestations of Defective Feet.

PMID- 18735170
TI  - Some Points on the Etiology and Treatment of Enuresis.

PMID- 18735171
TI  - Criminal Abortion.

PMID- 18735172
TI  - Report of Ophthalmological Cases.

PMID- 18735174
TI  - A Case of Primary Carcinoma of Bronchus in the Mediastinum.

PMID- 18735173
TI  - The Value of Rest in the Treatment of Pulmonary Tuberculosis.

PMID- 18735176
TI  - Two Case Reports by M. L. Emerson, M. D., Made to the Alameda County Medical
      Association.

PMID- 18735175
TI  - Crusade Against the Anophele Mosquito.

PMID- 18735177
TI  - Hook-Worm Disease Amongst Mexican Track Workers.

PMID- 18735179
TI  - Academy of Medicine.

PMID- 18735178
TI  - SOCIETY REPORTS.

PMID- 18735180
TI  - DR. MILLICAN GOES TO THE LANCET.

PMID- 18735181
TI  - Deaths.

PMID- 18735182
TI  - New Hospital for Post-Graduate Medical School.

PMID- 18735183
TI  - Opposition to Our Defense Plan.

PMID- 18735184
TI  - Systemic Gonorrheal Injection.

PMID- 18735185
TI  - On the Relief of Glaucoma by Subconjunctival Sodium Citrate Injections.

PMID- 18735186
TI  - Operative Treatment of Fractures of the Neck of the Femur.

PMID- 18735188
TI  - Artificial Cultivation of the Lepra Bacillus in Hawaii.

PMID- 18735187
TI  - Some Features of the Squirrel Plague Problem.

PMID- 18735189
TI  - A Case of Hernia in a Child.

PMID- 18735191
TI  - Non-union of Fracture.

PMID- 18735190
TI  - Acute Lymphatic Leukemia: Report of a Case.

PMID- 18735192
TI  - Diseases and Injuries to Knee Joint and Treatment of Same.

PMID- 18735193
TI  - REPORT OF FOUR CASES OF TUMOR OF THE CEREBELLO-PONTILE ANGLE.

PMID- 18735194
TI  - THE OPERATION TO EXPOSE THE CEREBELLO-PONTILE ANGLE.

PMID- 18735195
TI  - Three Cases of Probable Cancer Transplantation from the Use of the Gilman
      Vaccine.

PMID- 18735196
TI  - Demonstration of a Series of Sections of the Spinal Cord.

PMID- 18735198
TI  - PRACTICAL HYGIENE.

PMID- 18735197
TI  - SOCIETY REPORTS.

PMID- 18735199
TI  - ADVERTISING AGENCIES.

PMID- 18735200
TI  - CARE OF THE BODY.

PMID- 18735201
TI  - PROGRESS OR CARELESSNESS.

PMID- 18735203
TI  - NEWSPAPER INFLUENCE.

PMID- 18735202
TI  - INCREDULITY VS. GREATNESS.

PMID- 18735204
TI  - THE MOSZKOWICZ TEST.

PMID- 18735205
TI  - REMARKABLE SUIT WON.

PMID- 18735206
TI  - CAUSES OF DEATH.

PMID- 18735207
TI  - FEES FOR EXAMINATIONS.

PMID- 18735209
TI  - Acute Cholecystitis.

PMID- 18735208
TI  - VIAVI FAKES.

PMID- 18735210
TI  - ANNUAL MEETING.

PMID- 18735211
TI  - THE A. M. A. EXHIBIT HALL.

PMID- 18735212
TI  - MEDICAL DEFENSE.

PMID- 18735213
TI  - D-D HARD READING!

PMID- 18735214
TI  - INSURANCE EARNINGS.

PMID- 18735215
TI  - PROPRIETARIES GOOD AND BAD.

PMID- 18735216
TI  - WHY DO THEY DO IT?

PMID- 18735217
TI  - LEGISLATIVE HAPPENINGS.

PMID- 18735219
TI  - ANTITYPHOID VACCINATION.

PMID- 18735218
TI  - AN IMPROVED TECHNIC OF VACCINATION.

PMID- 18735220
TI  - The Commitment of the Insane in the State of California.

PMID- 18735221
TI  - The Municipal Refuse Disposal Problem, With Special Reference to Alameda County
      Conditions.

PMID- 18735222
TI  - Diseases of Domesticated Animals Affecting the Public Health in Alameda County.

PMID- 18735223
TI  - Notes on Sewage Disposal.

PMID- 18735225
TI  - The Making of a Health Officer.

PMID- 18735224
TI  - Opportunities of the State Hygienic Laboratory.

PMID- 18735227
TI  - Treatment of Rodent Ulcer.

PMID- 18735226
TI  - The Obstetric Consultant.

PMID- 18735228
TI  - Osteoplastic Operations in Pathologic Bone Cavities.

PMID- 18735229
TI  - Association of Milk Commissions.

PMID- 18735230
TI  - Report of a Case of Aneurysm of the Abdominal Aorta, with Operation and
      Introduction of Wire.

PMID- 18735231
TI  - Hookworm Disease Among Mexican Track Laborers.

PMID- 18735232
TI  - Department of Pharmacy and Chemistry.

PMID- 18735233
TI  - SOCIETY REPORTS.

PMID- 18735234
TI  - Regarding Malpractice Defense by the State Society.

PMID- 18735235
TI  - Corinna Borden Keen Research Fellowship of Jefferson Medical College.

PMID- 18735237
TI  - SQUIRREL ERADICATION.

PMID- 18735236
TI  - Micro-Organism Found in the Blood of Acute Cases of Poliomyelitis.

PMID- 18735238
TI  - CREDIT TO PUCK.

PMID- 18735239
TI  - RESEARCH IN PATHOLOGY.

PMID- 18735240
TI  - MALPRACTICE INSURANCE.

PMID- 18735242
TI  - CERTIFICATION OF BUTTER.

PMID- 18735241
TI  - CHRISTIE VS. SMITH.

PMID- 18735243
TI  - SCIENCE IN PHARMACEUTICS.

PMID- 18735244
TI  - PRODUCT PATENTS.

PMID- 18735246
TI  - THE PSYCHOTHERAPY WE NEED.

PMID- 18735245
TI  - Management of Labor in Cases of Contracted Pelvis.

PMID- 18735247
TI  - Factors Underlying the Cause and Treatment of Retrodisplacements.

PMID- 18735248
TI  - Tuberculous Ulceration of the Rectum.

PMID- 18735249
TI  - Rupture of the Liver-A Case Report and Comment.

PMID- 18735250
TI  - Skeletal Alignment and Muscular Balance in Their Relation to Pain, Function and
      Deformities.

PMID- 18735251
TI  - Abdominal Myomectomy During Pregnancy.

PMID- 18735252
TI  - A Simple Tonsil Dissector.

PMID- 18735253
TI  - Report of a Case of Thrombosis of the Central Retinal Vein.

PMID- 18735254
TI  - Xanthelasma.

PMID- 18735256
TI  - Department of Pathology, University of California.

PMID- 18735255
TI  - Medical Notes Taken in South America.

PMID- 18735257
TI  - A Case Report of Cortical Epilepsy.

PMID- 18735258
TI  - SOCIETY REPORTS.

PMID- 18735259
TI  - Resolutions on Contract Practice Adopted by the San Francisco County Medical
      Society.

PMID- 18735261
TI  - National Confederation of State Medical Examining and Licensing Boards.

PMID- 18735260
TI  - Anti-Meningitis Serum.

PMID- 18735262
TI  - Modern Hospital in Largest Hotel in the World.

PMID- 18735263
TI  - THE A. M. A. MEETING.

PMID- 18735265
TI  - SUMMER STUDY IN MEDICINE.

PMID- 18735264
TI  - THE ANNUAL MEETING.

PMID- 18735266
TI  - CHANGES IN MEDICAL LAW.

PMID- 18735267
TI  - NATURE OF THE CHANGES.

PMID- 18735268
TI  - FOR SALE AND LOCATIONS.

PMID- 18735270
TI  - THE LANE LECTURES.

PMID- 18735269
TI  - MEDICAL DEFENSE.

PMID- 18735271
TI  - Dr. John C. King.

PMID- 18735272
TI  - Address of the President.

PMID- 18735273
TI  - Report of the Secretary and Editor.

PMID- 18735274
TI  - Report of the Council.

PMID- 18735275
TI  - Report of the Board of Medical Examiners.

PMID- 18735277
TI  - Annual Report of the Public Health Committee of the Medical Society of the State
      of California.

PMID- 18735276
TI  - Report of the Committee on Contract and Lodge Practice.

PMID- 18735279
TI  - Scientific Exhibit, American Medical Association.

PMID- 18735278
TI  - The Section on Eye, Ear, Nose and Throat.

PMID- 18735280
TI  - Notes on a New Sign in Scarlet Fever.

PMID- 18735282
TI  - Intestinal Haemorrhage in Hernia.

PMID- 18735281
TI  - The Cell in Modern Medicine.

PMID- 18735283
TI  - The Skin as Influenced by the Thyroid Gland.

PMID- 18735284
TI  - The Diagnosis and Surgical Treatment of the Tuberculosis of the Kidney, With
      Report of Cases.

PMID- 18735285
TI  - Relation Between the Tonsils and Tubercle Bacilli.

PMID- 18735286
TI  - Society Reports.

PMID- 18735287
TI  - Lane Lectures.

PMID- 18735288
TI  - Referring Again to the Matter of Malpractice Defense by the Medical Society,
      State of California, and to a Certain Circular Letter Sent Out by a Private
      Malpractice Company.

PMID- 18735289
TI  - Summer Courses for Physicians.

PMID- 18735290
TI  - Department of Pharmacy and Chemistry.

PMID- 18735291
TI  - An Unfortunate Letter.

PMID- 18735292
TI  - The Ways of the Quacks.

PMID- 18735293
TI  - WHAT IS THE REASON?

PMID- 18735294
TI  - THE A. M. A. MEETING.

PMID- 18735295
TI  - LACK OF SUPPORT.

PMID- 18735296
TI  - WARNING TO PHYSICIANS.

PMID- 18735297
TI  - CHEAP WORK POOR WORK.

PMID- 18735298
TI  - TETANUS ANTITOXIN.

PMID- 18735299
TI  - SANE OR INSANE?

PMID- 18735300
TI  - THE LANE LECTURES.

PMID- 18735301
TI  - THE FOURTH OF-DEATH.

PMID- 18735303
TI  - DIAGNOSIS OF SCARLET FEVER.

PMID- 18735302
TI  - SALVARSAN, NEW INDICATIONS.

PMID- 18735304
TI  - THE CALIFORNIA ASSOCIATION OF MEDICAL MILK COMMISSIONS.

PMID- 18735305
TI  - The Experimental Basis of Vaccine Therapy.

PMID- 18735306
TI  - A Clinical View of Vaccine Therapy.

PMID- 18735308
TI  - The Diagnosis of Certain Intracranial Lesions.

PMID- 18735307
TI  - The Surgical Significance of Papilloedema.

PMID- 18735310
TI  - The Surgical Treatment of Subtentorial Cysts and Tumors.

PMID- 18735309
TI  - The Indications, Technic and Results in Decompressive Operations on the Brain.

PMID- 18735311
TI  - Functional Insufficiencies of the Myocardium.

PMID- 18735312
TI  - The Treatment of Hemoptysis in Tuberculosis.

PMID- 18735313
TI  - The Hypodermic Use of Hexamethylenanim.

PMID- 18735314
TI  - A Remarkable Case of Chickenpox.

PMID- 18735315
TI  - Removal of the Testicle-A Criticism by Dr. Mark Emerson.

PMID- 18735316
TI  - SOCIETY REPORTS.

PMID- 18735318
TI  - Army Medical Corps Examinations.

PMID- 18735317
TI  - Dr. H. J. Kreutzmann's Statement.

PMID- 18735319
TI  - The Lane Medical Lectures for 1911.

PMID- 18735320
TI  - PUBLIC HEALTH.

PMID- 18735321
TI  - THE A. M. A. MEETING.

PMID- 18735322
TI  - PRODUCT PATENTS.

PMID- 18735323
TI  - OF GREATEST IMPORTANCE.

PMID- 18735324
TI  - MEDICAL DEFENSE.

PMID- 18735325
TI  - EXTREME MODESTY.

PMID- 18735326
TI  - MEDICAL EDUCATION.

PMID- 18735328
TI  - COECUM MOBILE.

PMID- 18735327
TI  - A RAY OF SUNSHINE.

PMID- 18735329
TI  - Nasal Plastic With Auto-Transplantation of Bone.

PMID- 18735330
TI  - Intestinal Indigestion in Adults.

PMID- 18735331
TI  - Intestinal Indigestion From a Surgical Point of View.

PMID- 18735332
TI  - Report of a Case of Carcinoma of the Eyelid.

PMID- 18735333
TI  - Dermatitis Venenata From Proprietary Hair Dye.

PMID- 18735334
TI  - Report of a Case of Perforated Duodenal Ulcer, Operated Upon Fifty-five Hours
      After Perforation, Complicated by Double Pleuro-Pneumonia.

PMID- 18735335
TI  - The Modern Milk Feeding Station for Infants; Clinical Results.

PMID- 18735337
TI  - Border Line Cases of Ear Disease.

PMID- 18735336
TI  - Prevention of Post Obstetrical.

PMID- 18735338
TI  - The Significance and Treatment of Abdominal Pain.

PMID- 18735339
TI  - The Early Diagnosis and the Prophylaxis of the Toxemia of Pregnancy.

PMID- 18735340
TI  - Arteriosclerosis; Review of Cases.

PMID- 18735341
TI  - Treatment of Epithelioma by Curetting Followed by Cauterization With Chromic Acid
      and Later by Exposure to X-Ray.

PMID- 18735342
TI  - A New Tonsil Knife With a Description of Its Use.

PMID- 18735343
TI  - San Diego County.

PMID- 18735345
TI  - The Use of Digipuratum in Heart Disease.

PMID- 18735344
TI  - Translations and Abstracts.

PMID- 18735346
TI  - Marie Feodorovna Prize Competition to Be Held in Conjunction With the Ninth
      International Red Cross Conference, 1912.

PMID- 18735347
TI  - Lost or Stolen.

PMID- 18735349
TI  - TISSUE GROWTH IN VITRO.

PMID- 18735348
TI  - Psycho-Therapy.

PMID- 18735351
TI  - AURICULAR FIBRILLATION.

PMID- 18735350
TI  - PURELY PERSONAL.

PMID- 18735352
TI  - THE ETHER-RAUSCH ALONE.

PMID- 18735353
TI  - SOME DONT'S IN VACCINE THERAPY.

PMID- 18735354
TI  - IS CHEAP WORK POOR WORK?

PMID- 18735356
TI  - A Consideration of Mental Defectives.

PMID- 18735355
TI  - Clinical Observations on Migraine.

PMID- 18735357
TI  - A Resume of the Modern Operative Procedures in Ear Affections.

PMID- 18735358
TI  - The Control of Pathogenic Organisms in Butter.

PMID- 18735359
TI  - The Determination of Sex in the Human Species.

PMID- 18735361
TI  - Some Types of Intestinal Indigestion Occurring in Young Children.

PMID- 18735360
TI  - The Senile Skin.

PMID- 18735362
TI  - The Treatment of Tic in Childhood.

PMID- 18735364
TI  - Removal of Foreign Bodies From the Lung.

PMID- 18735363
TI  - Some Observations Relating to the Prophylaxis of Arthritis.

PMID- 18735366
TI  - A History of the Control of Tuberculosis in Three California Dairies.

PMID- 18735365
TI  - An Occipito-Atlantoid and an Atlanto-Axoid Dislocation.

PMID- 18735367
TI  - Regulations Governing the Manufacture of Certified Butter.

PMID- 18735368
TI  - Bovine Tuberculosis and Its Relation to the Public Health.

PMID- 18735369
TI  - The Prevalence of Bovine Tuberculosis.

PMID- 18735371
TI  - A Closed Incident.

PMID- 18735370
TI  - SOCIETY REPORTS.

PMID- 18735373
TI  - VARIOLA AND VARICELLA IN SAN FRANCISCO.

PMID- 18735372
TI  - JONNESCO AND SPINAL ANESTHESIA.

PMID- 18735374
TI  - THE EXCEPTIONAL CHILD.

PMID- 18735375
TI  - DISINFECTION OF THE SKIN.

PMID- 18735376
TI  - OPHTHALMOSCOPY IN MEDICINE.

PMID- 18735378
TI  - Treatment of Naevus Vascularis by the use of Carbon Dioxide Snow.

PMID- 18735377
TI  - Abnormal Body Temperatures in Injuries of the Cervical Spinal Cord.

PMID- 18735379
TI  - Mistakes in Medical Education.

PMID- 18735380
TI  - Some Points to be Considered in Feeding Infants.

PMID- 18735381
TI  - A Case of Carcinoma of the Appendix.

PMID- 18735383
TI  - SOCIETY REPORTS.

PMID- 18735382
TI  - Tentative Classification of Exceptional Children - Mental Test.

PMID- 18735384
TI  - PACIFIC COAST OTO-OPTHOLOGICAL SOCIETY.

PMID- 18735385
TI  - California Academy of Medicine.

PMID- 18735386
TI  - The Margaret Fahnestock Training School.

PMID- 18735387
TI  - Constipation.

PMID- 18735388
TI  - Medical Defense.

PMID- 18735389
TI  - ICTERUS BY HEMOLYSIS.

PMID- 18735390
TI  - SOMETHING INTERSTITIAL.

PMID- 18735391
TI  - A SKIN REACTION IN SYPHILIS.

PMID- 18735392
TI  - RAT LEPROSY.

PMID- 18735394
TI  - A SIMPLIFIED MATERIA MEDICA.

PMID- 18735393
TI  - DIORADINE.

PMID- 18735396
TI  - THE TEACHING OF OBSTETRICS.

PMID- 18735395
TI  - AN INNOVATION.

PMID- 18735397
TI  - Geographic Influences in the Etiology of Skin Disease.

PMID- 18735398
TI  - The Toxemias of Pregnancy.

PMID- 18735399
TI  - Some Points to be Considered in Feeding Infants.

PMID- 18735400
TI  - Unusual Cases of Syphilitic Osteoperiostitis.

PMID- 18735401
TI  - Tentative Classification of Exceptional Children.

PMID- 18735402
TI  - The Differential Diagnosis of Labyrinthine Affections.

PMID- 18735403
TI  - SOCIETY REPORTS.

PMID- 18735404
TI  - SALVARSAN.

PMID- 18735405
TI  - CANCER.

PMID- 18735406
TI  - CLASSIFICATION OF LEUCOCYTES.

PMID- 18735407
TI  - USE OF PITUITRIN IN OBSTETRICS.

PMID- 18735408
TI  - BRILL'S SYMPTOM COMPLEX AND TYPHUS FEVER.

PMID- 18735410
TI  - IMMUNITY.

PMID- 18735411
TI  - SPECIALISM.

PMID- 18735409
TI  - MYOCARDIAL DEGENERATION.

PMID- 18735412
TI  - THE VALUE OF EDEBOHL'S OPERATION IN CHRONIC NEPHRITIS.

PMID- 18735414
TI  - A Practical Method of Artificial Feeding.

PMID- 18735413
TI  - The Significance of Pelvic Pain.

PMID- 18735415
TI  - The Prostate in Chronic Gonorrhea.

PMID- 18735416
TI  - The Differential Diagnosis of Labyrinthine Affections.

PMID- 18735417
TI  - The Eye and Its Semeiological Aspect.

PMID- 18735418
TI  - Report on Contract Practice.

PMID- 18735419
TI  - Tentative Classification of Exceptional Children-Physical Test.

PMID- 18735420
TI  - Cooper College Science Club.

PMID- 18735421
TI  - Some Observations on Goitre.

PMID- 18735422
TI  - California Academy of Medicine.

PMID- 18735423
TI  - Army Medical Corps Examinations.

PMID- 18735424
TI  - Bismuth-Iodin Paste in Discharging Sinuses.

PMID- 18735425
TI  - Special Study in Pellagra.

PMID- 18735426
TI  - Report of Hospital Commission of the San Francisco County Medical Society.

PMID- 18735427
TI  - Tropical Medicine.

PMID- 18735428
TI  - Transmission of Disease by Means of Books.

PMID- 18735429
TI  - Ethical Rules for the Guidance of Physicians and Pharmacists in Their Relations
      With Each Other and With the Public.

PMID- 18735430
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18735431
TI  - New and Non-Official Remedies.

PMID- 18735432
TI  - The Relation of the Vacuum-Cleaner Machine to the Public Health.

PMID- 18735433
TI  - Woman's Pharmaceutical Association.

PMID- 18735434
TI  - DIORADIN ONCE MORE.

PMID- 18735435
TI  - REPORT OF A CASE OF POLYCYTHEMIA.

PMID- 18735436
TI  - EXTRAORDINARY TEMPERATURES.

PMID- 18735437
TI  - ANALYSIS OF TREATMENT OF SIXTY-TWO CASES OF SYPHILIS WITH SALVARSAN.

PMID- 18735438
TI  - THE SECOND DECADE.

PMID- 18735439
TI  - BY HIS WORKS.

PMID- 18735440
TI  - EXCERPTS FROM RECENT ITALIAN EYE LITERATURE.

PMID- 18735441
TI  - A CASE OF MALIGNANT EDEMA.

PMID- 18735442
TI  - MULTIPLE PAPILLOMATA OF THE LARYNX IN CHILDREN-REPORT OF TWO CASES.

PMID- 18735443
TI  - SELECTED CHAPTERS IN THE STUDY OF SPEECH DISTURBANCES. NO. 2.-THE RESPONSIBILITY
      OF THE GENERAL PRACTITIONER TO THE CHILD WITH A SPEECH DEFECT, WITH SUGGESTIONS
      AS TO PROPHYLACTICS.

PMID- 18735445
TI  - EXTRA-MEDICAL PROSELYTING.

PMID- 18735444
TI  - MECHANICAL EFFICIENCY.

PMID- 18735446
TI  - SALVARSAN-A WARNING.

PMID- 18735447
TI  - A CASE OF BROWN-SEQUARD'S PARALYSIS FOLLOWING A STAB WOUND OF THE BACK.

PMID- 18735448
TI  - SOME MISINTERPRETATIONS IN THE TEACHING OF GROSS ANATOMY.

PMID- 18735449
TI  - TRANSFUSION IN A CASE OF TYPHOID FEVER.

PMID- 18735450
TI  - HOSPITAL DEPARTMENT - SAN FRANCISCO HOSPITALS.

PMID- 18735451
TI  - DRUG THERAPY.

PMID- 18735453
TI  - HOSPITAL DEPARTMENT.

PMID- 18735452
TI  - MEDICAL DEFENSE.

PMID- 18735455
TI  - COOPER COLLEGE OF SCIENCE.

PMID- 18735454
TI  - PERMANENT SUPRAPUBIC DRAINAGE OF THE BLADDER WITHOUT LEAKAGE-DEMONSTRATION OF A
      CASE.

PMID- 18735456
TI  - DIAGNOSTIC TABLE.

PMID- 18735457
TI  - CALIFORNIA ACADEMY OF MEDICINE.

PMID- 18735458
TI  - UNJUSTIFIABLE CRUELTY.

PMID- 18735459
TI  - HITCHCOCK LECTURES.

PMID- 18735460
TI  - PUBLIC HEALTH AND ITS FOES.

PMID- 18735461
TI  - SPOROTRICHOSIS.

PMID- 18735462
TI  - THE EYE IN ITS SEMEIOLOGICAL ASPECT.

PMID- 18735464
TI  - THE PLAN IN GENERAL.

PMID- 18735463
TI  - A PLEA FOR THE EARLIER RADICAL SURGICAL TREATMENT OF GASTRIC ULCER.

PMID- 18735465
TI  - MEDICAL DEFENSE.

PMID- 18735466
TI  - OWEN BILL.

PMID- 18735467
TI  - EXPLOITERS OF NOSTRUMS.

PMID- 18735468
TI  - WHAT DO YOU THINK?

PMID- 18735469
TI  - SURGEON-GENERAL RUPERT BLUE.

PMID- 18735470
TI  - DOCTOR WILEY.

PMID- 18735471
TI  - ORIGINAL ARTICLES.

PMID- 18735472
TI  - A SKIN REACTION IN SYPHILIS.

PMID- 18735473
TI  - TYPHOID VACCINATION.

PMID- 18735475
TI  - CONTRACT PRACTICE.

PMID- 18735474
TI  - MEDICAL DEFENSE.

PMID- 18735476
TI  - MEDICAL ORGANIZATIONS AND CONSERVATION OF THE PUBLIC HEALTH: President's Address
      at the Annual Meeting of the Los Angeles County Medical Association, December
      15th, 1911.

PMID- 18735477
TI  - SOME REMARKS ON SO-CALLED "AUTOMOBILE FRACTURES.".

PMID- 18735478
TI  - THE LIPOIDS OF NORMAL, NEPHRITIC AND DIABETIC SERUM: PRELIMINARY REPORT.

PMID- 18735479
TI  - SAN FRANCISCO COUNTY-Committee on Necrology Report.

PMID- 18735480
TI  - INTERSCAPULAR-THORACIC AMPUTATION.

PMID- 18735481
TI  - SELECTED CHAPTERS IN THE STUDY OF SPEECH DISTURBANCES. NO. 2.-THE RESPONSIBILITY
      OF THE GENERAL PRACTITIONER TO THE CHILD WITH A SPEECH DEFECT, WITH SUGGESTIONS
      AS TO PROPHYLACTICS.

PMID- 18735482
TI  - CALIFORNIA ACADEMY OF MEDICINE.

PMID- 18735483
TI  - COOPER COLLEGE SCIENCE CLUB.

PMID- 18735484
TI  - SOCIETY REPORTS.

PMID- 18735485
TI  - THE DRUG EVIL.

PMID- 18735487
TI  - CLINIC REPORT.

PMID- 18735486
TI  - THE OWEN BILL: Sixty-second Congress, First Session-S. 1.

PMID- 18735489
TI  - RED CROSS.

PMID- 18735488
TI  - HISTORY OF A PECULIAR CASE.

PMID- 18735491
TI  - LANE LECTURES, 1912.

PMID- 18735490
TI  - DR. GEORGE W. McCOY.

PMID- 18735492
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18735493
TI  - TYPICAL "PATENT MEDICINE" LITERATURE.

PMID- 18735494
TI  - MILITARY HYGIENE.

PMID- 18735495
TI  - Foolish Stuff-Not to Be Taken Seriously.

PMID- 18735496
TI  - THE MANAGEMENT OF CASES OF PULMONARY TUBERCULOSIS; WITH REMARKS ON TREATMENT.

PMID- 18735497
TI  - THE CHEMISTRY OF PREPARING SALVARSAN FOR INJECTION AND A SIMPLE, RAPID METHOD FOR
      ITS PREPARATION.

PMID- 18735498
TI  - VARIATIONS IN THE TONICITY OF THE ABDOMINAL MUSCULATURE AND THEIR SIGNIFICANCE.

PMID- 18735499
TI  - TREATMENT OF VASCULAR NAEVI WITH CARBON DIOXIDE SNOW.

PMID- 18735500
TI  - MEDICAL LAWS OF CALIFORNIA.

PMID- 18735502
TI  - HENRY GIBBONS, JR.

PMID- 18735501
TI  - A CASE OF PARTIAL TREMULOUS SCRIVENER'S PALSY: The Psychogenesis of Which Was
      Discovered in One Interview Which Led to Recovery Through the Patient's Own
      Effort.

PMID- 18735503
TI  - VERY LARGE CALCULUS, AND DEMONSTRATIONS.

PMID- 18735504
TI  - RABIES AND THE PASTEUR TREATMENT.

PMID- 18735505
TI  - TREASURY DEPARTMENT: Bureau of Public Health and Marine-Hospital Service.

PMID- 18735506
TI  - FAITH OR FACT: An editorial in the Fresno Republican, Feb. 5th, 1912.

PMID- 18735507
TI  - IGNORANCE-AND GRAFT.

PMID- 18735508
TI  - COMMITTEE ON PAPERS, C. Ph. A., ISSUES CALL.

PMID- 18735509
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18735510
TI  - DO MEN THINK?

PMID- 18735511
TI  - ANOTHER EXAMPLE.

PMID- 18735512
TI  - PUBLICITY CAMPAIGN.

PMID- 18735513
TI  - SOUND VIEWS.

PMID- 18735515
TI  - THE PRESS AND PATENT MEDICINE.

PMID- 18735514
TI  - QUALITY OF PAPERS.

PMID- 18735516
TI  - VALUE OF LITTLE THINGS.

PMID- 18735517
TI  - MEDICAL EDUCATION.

PMID- 18735518
TI  - FUNCTIONAL DIAGNOSIS-A FERTILE FIELD.

PMID- 18735519
TI  - RECENT ADVANCES IN REGIONAL (LOCAL) ANESTHESIA.

PMID- 18735520
TI  - ANESTHETICS, METHODS AND INDICATIONS.

PMID- 18735521
TI  - A COUPLE OF FAKES.

PMID- 18735522
TI  - RECORD YOUR CERTIFICATE.

PMID- 18735523
TI  - NEW YORK STATISTICS.

PMID- 18735524
TI  - MORE "STATE MEDICINE.".

PMID- 18735525
TI  - EDDYISM FLIP-FLOP.

PMID- 18735526
TI  - A PROUD SOCIETY.

PMID- 18735527
TI  - CHINOSOL APPROVED.

PMID- 18735528
TI  - ANOTHER WHY?

PMID- 18735529
TI  - NEWS ITEMS OF INTEREST.

PMID- 18735530
TI  - HYDROPHOBIA.

PMID- 18735531
TI  - THE LIFE OF RADIUM AND ITS THERAPEUTIC USE IN INTERNAL MEDICINE.

PMID- 18735532
TI  - THE ECONOMIC VALUE OF THE DECIDUOUS TEETH.

PMID- 18735533
TI  - REPORT OF MASTOID CASES WITH SPECIAL REFERENCE TO DIAGNOSIS.

PMID- 18735534
TI  - RATIONAL SURGERY OF RETRO-BULBAR NEOPLASMS, WITH REPORT OF A CASE OF CYLINDROMA
      OF THE ORBIT, EXTIRPATION OF SAME AND PRESERVATION OF THE EYE.

PMID- 18735535
TI  - A GENERAL CONSIDERATION OF SOME POINTS OF INTEREST IN THE DIAGNOSIS AND TREATMENT
      OF SYPHILIS.

PMID- 18735536
TI  - AN EXPERIMENTAL STUDY OF A REMARKABLE CASE OF NEPHRITIS WITH EMPYEMA OF THE
      CRANIAL SINUSES AND MILKY SERUM: Contribution to the Literature of Fat
      Metabolism.

PMID- 18735537
TI  - RESULTS OBTAINED WITH A MODIFIED VACCINE: A Report of Ninety Cases.

PMID- 18735538
TI  - REPORT OF A CASE OF SINUS THROMBUS DUE TO WELCH GAS BACILLUS.

PMID- 18735539
TI  - IMPORTANT POINTS IN THE EARLY RECOGNITION AND DIFFERENTIATION OF SOME DISEASES OF
      THE NERVOUS SYSTEM.

PMID- 18735541
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18735540
TI  - STRANGULATED FEMORAL HERNIA CONTAINING AN UNDEVELOPED KIDNEY.

PMID- 18735543
TI  - VACCINATION LAW.

PMID- 18735542
TI  - PACIFIC COAST OTO-OPHTHALMOLOGICAL SOCIETY.

PMID- 18735544
TI  - SOCIETY REPORTS.

PMID- 18735545
TI  - DR. ELIAS S. COOPER, SURGEON.

PMID- 18735546
TI  - "DR. MENZ; A WARNING!

PMID- 18735548
TI  - CHINOSOL CRITICISED IN ERROR.

PMID- 18735547
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18735550
TI  - DOCTOR WILEY.

PMID- 18735549
TI  - IN FREEDOM'S NAME.

PMID- 18735552
TI  - PROTECTING A GULLIBLE PUBLIC.

PMID- 18735551
TI  - THE RECORD AND WILEY.

PMID- 18735553
TI  - KEEP IT IN YOUR OFFICE.

PMID- 18735554
TI  - SOMEWHAT SHADY.

PMID- 18735555
TI  - SOME WHYS.

PMID- 18735556
TI  - HUMOROSITY EVERYWHERE.

PMID- 18735557
TI  - TREATMENT OF SEVERE CASES OF DIABETES.

PMID- 18735558
TI  - SOME CASES SUCCESSFUL AND OTHERWISE, BEING A REPORT OF TWO CASES, SINUS
      THROMBOSIS AND A CASE OF RETROPHARYNGEAL ABSCESS.

PMID- 18735559
TI  - THE BLOOD PRESSURE IN PNEUMONIA.

PMID- 18735560
TI  - SPECIAL FACTORS CONCERNING SURGERY OF CANCER OF THE LIP AND TONGUE.

PMID- 18735561
TI  - SALVARSAN IN CUTANEOUS SYPHILIS.

PMID- 18735562
TI  - THE INTRAVENOUS APPLICATION OF SALVARSAN, WITH SPECIAL REFERENCE TO ITS TECHNIC.

PMID- 18735563
TI  - ALCOHOLIC INJECTION OF SUPERIOR LARYNGEAL NERVE.

PMID- 18735564
TI  - CHOICE OF TECHNIC IN HYSTERECTOMY.

PMID- 18735565
TI  - THE TREATMENT OF URETHRITIS IN THE MALE.

PMID- 18735567
TI  - CASE REPORTS.

PMID- 18735566
TI  - THE TREATMENT OF SPINAL CURVATURE.

PMID- 18735568
TI  - HYDRONEPHROSIS.

PMID- 18735569
TI  - FATAL CASE OF SYPHILITIC MYELITIS AFTER INTRAMUSCULAR INJECTION OF SALVARSAN.

PMID- 18735570
TI  - GIBBONS MEMORIAL.

PMID- 18735571
TI  - LATE RESULT IN A CASE OF TRAUMATIC EPILEPSY.

PMID- 18735572
TI  - TONSILLECTOMY COMPLICATED BY POST-DIPHTHERITIC PARESIS.

PMID- 18735573
TI  - SOCIETY REPORTS.

PMID- 18735574
TI  - NAMES OF MEDICAL PREPARATIONS.

PMID- 18735575
TI  - ANOTHER LIQUID SULPHUR FAKE.

PMID- 18735576
TI  - PAPYRUS EBERS.

PMID- 18735577
TI  - BE YE HUMANE.

PMID- 18735578
TI  - IMPORTANT CHANGES.

PMID- 18735579
TI  - "SOME MEN ARE BORN GREAT," ETC.

PMID- 18735580
TI  - MISDIRECTED ADVERTISING.

PMID- 18735581
TI  - ONCE MORE.

PMID- 18735582
TI  - ASSOCIATION BULLETIN.

PMID- 18735583
TI  - CONVULSIONS IN MEDICAL COLLEGES.

PMID- 18735584
TI  - A SECRETARY'S VIEWS ON DUES.

PMID- 18735585
TI  - BOARD OF EXAMINERS.

PMID- 18735586
TI  - THOMAS W. HUNTINGTON, A. B., M. D.

PMID- 18735587
TI  - ADDRESS OF THE PRESIDENT: THE MEDICAL EDUCATION PROBLEM.

PMID- 18735588
TI  - REPORT OF THE SECRETARY AND EDITOR.

PMID- 18735589
TI  - REPORT OF THE COUNCIL.

PMID- 18735590
TI  - REPORT OF THE COMMITTEE ON CANCER.

PMID- 18735591
TI  - AUDITOR'S REPORT.

PMID- 18735593
TI  - THE TREATMENT OF SPINAL CURVATURE.

PMID- 18735592
TI  - REPORT OF THE COMMITTEE APPOINTED TO STUDY THE EFFECT OF ATHLETICS UPON THE
      PUPILS IN OUR SCHOOLS AND COLLEGES.

PMID- 18735594
TI  - HYPOPHYSIS DISEASES AND THEIR DIAGNOSIS.

PMID- 18735596
TI  - REPORT OF THE SECRETARY OF THE CALIFORNIA ASSOCIATION FOR THE STUDY AND
      PREVENTION OF TUBERCULOSIS, 1911-12.

PMID- 18735595
TI  - REPORT ON MEDICAL EDUCATION.

PMID- 18735597
TI  - THE PATHOLOGICAL CONDITIONS OF THE EYE SECONDARY TO DISEASE OF THE LYMPHATICS OF
      THE NECK AND THROAT.

PMID- 18735598
TI  - A PROPOSED CODE OF PUBLIC HEALTH REGULATIONS FOR CALIFORNIA.

PMID- 18735599
TI  - THE OPERATIVE PROCEDURE IN HYPOPHYSEAL AFFECTIONS.

PMID- 18735600
TI  - REGULATION OF HOSPITALS.

PMID- 18735601
TI  - SOCIETY REPORTS.

PMID- 18735602
TI  - CALIFORNIA ACADEMY OF MEDICINE.

PMID- 18735603
TI  - A State Organization for the Consideration of Public and Personal Hygiene.

PMID- 18735604
TI  - NURSES' ASSOCIATION.

PMID- 18735605
TI  - ATTENDANCE AT THE ANNUAL MEETINGS.

PMID- 18735606
TI  - OUR EXHIBITS AND EXHIBITORS.

PMID- 18735608
TI  - TESTIMONIAL TO DR. H. BERT ELLIS.

PMID- 18735607
TI  - RESEARCH EXPEDITION.

PMID- 18735609
TI  - THE BARLOW SANATORIUM.

PMID- 18735610
TI  - THE VALUE OF A "PATENT MEDICINE.": "Syrup of Figs" Goes to Wheeling Syndicate.

PMID- 18735611
TI  - ARMY MEDICAL CORPS EXAMINATION.

PMID- 18735612
TI  - PROFESSOR LONG.

PMID- 18735614
TI  - CATCHING SUCKERS.

PMID- 18735613
TI  - SUGGESTIONS TO AUTHORS.

PMID- 18735615
TI  - TRUTH OR LIES.

PMID- 18735616
TI  - A NEW GOLD BRICK PLANT.

PMID- 18735617
TI  - THE BARANY SYMPTOM COMPLEX.

PMID- 18735618
TI  - SALVARSAN AGAIN.

PMID- 18735619
TI  - ON MAKING BOOKS.

PMID- 18735620
TI  - THE PRESENT STATUS OF NITROUS OXIDE IN MAJOR SURGERY.

PMID- 18735621
TI  - THE CHOICE OF AN ANESTHETIC.

PMID- 18735622
TI  - MISHAPS IN TREATMENT.

PMID- 18735623
TI  - AN EPIDEMIC OF TRICHINOSIS.

PMID- 18735624
TI  - THE COUNTY HEALTH OFFICER AS THE LOCAL REGISTRAR FOR EACH COUNTY IN THE STATE.

PMID- 18735626
TI  - DIAPHRAGMATIC PLEURISY: A Stumbling Block in the Consideration of the Acute
      Abdomen.

PMID- 18735625
TI  - HYGIENIC LABORATORY OF THE STATE BOARD OF HEALTH.

PMID- 18735627
TI  - ANTITYPHOID VACCINATION.

PMID- 18735628
TI  - THE TUBERCULIDES AS OBSERVED IN SOUTHERN CALIFORNIA.

PMID- 18735629
TI  - THE INTERRELATIONSHIP BETWEEN THE MOTOR AND SECRETORY FUNCTIONS OF THE STOMACH.

PMID- 18735630
TI  - ORBITAL ENDOTHELIOMA-REPORT OF CASE.

PMID- 18735631
TI  - A REPORT OF TWENTY-EIGHT CASES OF TROPICAL ABSCESS OF THE LIVER.

PMID- 18735632
TI  - MECHANISM AND CLINICAL ASPECTS OF CHRONIC ARTERIAL HYPERTENSION.

PMID- 18735634
TI  - CLINICAL ASPECTS OF UROSEPSIS.

PMID- 18735633
TI  - DIAGNOSTIC VALUE OF PASTIA'S SIGN IN SCARLET FEVER.

PMID- 18735635
TI  - REPORT OF AN INTERESTING CEREBRAL CASE.

PMID- 18735637
TI  - THE CALIFORNIA ACADEMY OF MEDICINE.

PMID- 18735636
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18735639
TI  - PROFESSIONAL OPTIMISM.

PMID- 18735638
TI  - SOCIETY REPORTS.

PMID- 18735640
TI  - MISPLACED UNEASINESS.

PMID- 18735641
TI  - FREE TREATMENT FOR RABIES.

PMID- 18735642
TI  - WORKS WORDS.

PMID- 18735643
TI  - WONDER OF WONDERS!

PMID- 18735644
TI  - A GRAFTER WITH US.

PMID- 18735645
TI  - SERIOUS HORRORS.

PMID- 18735646
TI  - A REPLY.

PMID- 18735647
TI  - SEX IN RELATION TO SOCIETY.

PMID- 18735648
TI  - PONTIFICAL AIRS, FORSOOTH!

PMID- 18735649
TI  - RABIES, AND ITS PRESENT STATUS IN CALIFORNIA.

PMID- 18735650
TI  - CLINICAL SYMPTOMS OF ALCOHOLISM AND ITS TREATMENT.

PMID- 18735651
TI  - EXPERIMENTAL SURGERY OF THE HYPOPHYSIS CEREBRI.

PMID- 18735652
TI  - CLINICAL VALUE OF THE ARNETH METHOD OF BLOOD EXAMINATION.

PMID- 18735653
TI  - A CASE OF ACROMEGALY WITH THROMBOSIS AND EMBOLISM.

PMID- 18735654
TI  - THE PRESENT AND FUTURE OF THE EYE AND EAR SECTION OF OUR STATE MEDICAL SOCIETY.

PMID- 18735655
TI  - OCULAR DISTURBANCES CAUSED BY THE CINEMATOGRAPH.

PMID- 18735656
TI  - THE CALIFORNIA STATE TUBERCULOSIS COMMISSION.

PMID- 18735658
TI  - SOCIETY REPORTS.

PMID- 18735657
TI  - APPENDICITIS: THEN AND NOW.

PMID- 18735659
TI  - CHESTER ROWELL, M. D.

PMID- 18735660
TI  - WILLIAM L. MAUPIN, M. D.

PMID- 18735661
TI  - EXPERT TESTIMONY: Resolutions Regarding Expert Engineering or Technical Testimony
      Adopted by the Pacific Association of Consulting Engineers, December 1, 1911.

PMID- 18735662
TI  - REASONABLE PROTEST; HEED IT.

PMID- 18735663
TI  - THE PHARMACIST AS THE PHYSICIAN'S MENTOR.

PMID- 18735664
TI  - NEW AND NONOFFICIAL REMEDIES.

PMID- 18735665
TI  - TAKA-DIASTASE AGAIN FOUND WANTING.

PMID- 18735666
TI  - FAILURE OF THE INSURANCE BILL.

PMID- 18735667
TI  - FANATICAL ATTACKS.

PMID- 18735668
TI  - WHY THIS INVASION?

PMID- 18735669
TI  - CARELESS CRITICS.

PMID- 18735670
TI  - SHAC.

PMID- 18735671
TI  - PLATFORMS AND HEALTH.

PMID- 18735673
TI  - COLLECTING ACCOUNTS.

PMID- 18735672
TI  - TUBERCULOSIS SUNDAY.

PMID- 18735674
TI  - TAKING A VACATION?

PMID- 18735675
TI  - EPIDEMIC OF POLIOMYELITIS.

PMID- 18735676
TI  - MORE NAMES.

PMID- 18735678
TI  - THE COLLECTION BUREAU PLAN OF THE LOS ANGELES COUNTY MEDICAL ASSOCIATION.

PMID- 18735677
TI  - RECENT CONCLUSIONS REGARDING SYPHILIS.

PMID- 18735680
TI  - EHRLICH'S 606 IN EUROPE.

PMID- 18735679
TI  - PROGRESS IN THE DIAGNOSIS AND TREATMENT OF SYPHILIS.

PMID- 18735681
TI  - THE ABORTIVE TREATMENT OF SYPHILIS.

PMID- 18735682
TI  - SALVARSAN VS. MERCURY.

PMID- 18735683
TI  - THE FALLIBILITY OF SALVARSAN.

PMID- 18735684
TI  - SALVARSAN IN VARIOUS MEDICAL DISORDERS ASSOCIATED WITH A WASSERMANN REACTION.

PMID- 18735685
TI  - BARANY'S INVESTIGATION ON LOCALIZATION IN THE CEREBELLUM.

PMID- 18735686
TI  - GENERAL ANESTHESIA IN CATARACT WORK.

PMID- 18735687
TI  - RADIOLOGICAL INVESTIGATION OF THE DISEASES OF THE STOMACH.

PMID- 18735688
TI  - THE DIAGNOSIS OF LATENT GONORRHEA IN THE FEMALE.

PMID- 18735689
TI  - THE CLINICAL FEATURES AND NEUROLOGICAL FINDINGS IN POLIOMYELITIS.

PMID- 18735690
TI  - NECROSIS OF THE HYOID BONE.

PMID- 18735691
TI  - SOCIETY REPORTS.

PMID- 18735692
TI  - SOUTHERN CALIFORNIA PUBLIC HEALTH ASSOCIATION.

PMID- 18735693
TI  - IMPORTANT INFORMATION RELATING TO REPORTING INDUSTRIAL ACCIDENTS.

PMID- 18735694
TI  - THE PEOPLE WILL SUFFER.

PMID- 18735695
TI  - DOES IT PAY?

PMID- 18735696
TI  - A WORD ON CRITICISM.

PMID- 18735697
TI  - JOKER IN DRUG BILL.

PMID- 18735698
TI  - FOURTH OF JULY.

PMID- 18735699
TI  - QUESTIONABLE ASSOCIATES?

PMID- 18735700
TI  - MAZDAZNAN EXTENSION.

PMID- 18735702
TI  - THE SKIN REACTION IN SYPHILIS.

PMID- 18735701
TI  - SEND THE STICKERS.

PMID- 18735703
TI  - MEDICAL EDUCATION IN EUROPE. THE CARNEGIE FOUNDATION FOR THE ADVANCEMENT OF
      TEACHING, 1912.

PMID- 18735704
TI  - SPECIAL REPORT ON POLIOMYELITIS: EPIDEMIC POLIOMYELITIS IN LOS ANGELES.

PMID- 18735705
TI  - SYMPOSIUM ON THE WASSERMAN REACTION AND SALVARSAN TREATMENT IN SYPHILIS:
      CONCLUDED: SALVARSAN IN OBSTINATE LATE SYPHILITIC LESIONS OF THE PALMS, SOLES,
      AND MUCOUS MEMBRANES OF THE MOUTH.

PMID- 18735706
TI  - SALVARSAN IN SYPHILITIC DISEASE OF THE NERVOUS SYSTEM.

PMID- 18735707
TI  - A PRELIMINARY REPORT ON TWENTY-THREE CHILDREN TREATED WITH SALVARSAN.

PMID- 18735708
TI  - EARLY DIAGNOSIS OF EPIDEMIC POLIOMYELITIS.

PMID- 18735710
TI  - THE DREAM-STATE OF DELIRIUM TREMENS AND THE INADEQUACY OF THE CALIFORNIA STATUTES
      IN NOT COVERING CERTAIN CONDITIONS OF IRRESPONSIBILITY FOR CRIME, EXEMPLIFIED IN
      AN UNUSUAL CASE.

PMID- 18735709
TI  - THREE CLOSELY ASSOCIATED CASES OF ACUTE POLIOMYELITIS.

PMID- 18735712
TI  - SOCIETY REPORTS.

PMID- 18735711
TI  - CHRONIC INTESTINAL STASIS.

PMID- 18735713
TI  - THE LATE JOHN FIFE, M. D.

PMID- 18735714
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18735715
TI  - NEW AND NONOFFICIAL REMEDIES.

PMID- 18735716
TI  - USE OF TYPHOID VACCINES.

PMID- 18735717
TI  - GERMAN PROPRIETARIES AND PATRIOTISM.

PMID- 18735718
TI  - RELATING TO HEALTH SUPERVISION OF SCHOOL CHILDREN.

PMID- 18735719
TI  - REFLECTIONS OF A PLAIN BUSINESS MAN.

PMID- 18735720
TI  - PUBLIC HEALTH SERVICE.

PMID- 18735721
TI  - ENCOURAGING APPROVAL.

PMID- 18735722
TI  - PESSIMISM OR SENSE?

PMID- 18735723
TI  - "STRAW MAN" OR FOOL-MAN?

PMID- 18735724
TI  - ANOMALOUS CONDITIONS.

PMID- 18735725
TI  - OHIO'S PLIGHT.

PMID- 18735726
TI  - CHANGES COMING.

PMID- 18735727
TI  - CHANGE IN LAW.

PMID- 18735728
TI  - APPRECIATION? NO! ABUSE!

PMID- 18735729
TI  - BITING FLY INDICTED.

PMID- 18735730
TI  - "STICKERS" BRING COIN.

PMID- 18735731
TI  - EDDYITE PROFITS.

PMID- 18735732
TI  - IMPORTANT MEETINGS.

PMID- 18735733
TI  - THE VALUE OF PRISMS IN EYE STRAIN.

PMID- 18735734
TI  - LABOR IN MODERATELY CONTRACTED PELVES WITH SPECIAL REFERENCE TO CESAREAN SECTION.

PMID- 18735735
TI  - OPERATIVE AND POST-OPERATIVE TONSILLAR HEMORRHAGE.

PMID- 18735736
TI  - THROMBOSIS OF THE SIGMOID SINUS AND JUGULAR VEIN, FROM DIRECT TYMPANIC INFECTION
      OF THE JUGULAR BULB. A REPORT OF TWO CASES.

PMID- 18735737
TI  - SOME OPINIONS CONCERNING TONSIL SURGERY.

PMID- 18735738
TI  - REVIEW OF RECENT ITALIAN EYE LITERATURE.

PMID- 18735739
TI  - PATULOUS ANUS: ITS CLINICAL SIGNIFICANCE.

PMID- 18735740
TI  - REPORT OF A CASE OF STENOSIS OF THE DUODENUM DUE TO GALL STONES; OPERATION;
      RECOVERY.

PMID- 18735741
TI  - A FEW POINTS IN REGARD TO CANCER OF THE UTERUS.

PMID- 18735743
TI  - THE SIGNIFICANCE OF BACTERIA IN MILK.

PMID- 18735742
TI  - A CONTRIBUTION TO THE SUBJECT OF PELLAGRA IN CALIFORNIA.

PMID- 18735744
TI  - HEREDITARY PIGMENTED NEVUS?

PMID- 18735745
TI  - REPORT OF A CASE OF PYEMIA.

PMID- 18735746
TI  - A CASE OF COMPLETE TRANSPOSITION OF THE VISCERA.

PMID- 18735748
TI  - CAN THIS CIRCULAR BE A JOKE?

PMID- 18735747
TI  - SOCIETY REPORTS.

PMID- 18735749
TI  - DR. VON NOORDEN'S VISIT.

PMID- 18735750
TI  - SOCIETY FOR THE PREVENTION OF BLINDNESS.

PMID- 18735752
TI  - WHAT IS MEMBERSHIP WORTH?

PMID- 18735751
TI  - NEW AND NONOFFICIAL REMEDIES.

PMID- 18735754
TI  - PRESIDENT'S MESSAGE.

PMID- 18735753
TI  - TENTH VOLUME.

PMID- 18735756
TI  - MEDICAL DEFENSE.

PMID- 18735755
TI  - DOCTOR OR DANGER?

PMID- 18735757
TI  - NOTABLE MEETING.

PMID- 18735758
TI  - UNFOUNDED CRITICISM.

PMID- 18735759
TI  - MEDICAL DEFENSE.

PMID- 18735760
TI  - DIET IN HOSPITALS.

PMID- 18735761
TI  - GOOD RULES.

PMID- 18735763
TI  - GEORGIA'S TROUBLES.

PMID- 18735762
TI  - NOBEL PRIZE.

PMID- 18735764
TI  - CONSIDERATION AND TREATMENT OF SOME DISEASES OF THE UPPER AIR PASSAGES IN SINGERS
      AND PUBLIC SPEAKERS.

PMID- 18735765
TI  - A CONSIDERATION OF SOME OF THE CONDITIONS COMMONLY CALLED "RHEUMATISM.".

PMID- 18735766
TI  - THE RELATION OF PAIN, ESPECIALLY BACKACHE, TO JOINT STRAIN, OR THE RELATION OF
      PAIN TO MECHANICS.

PMID- 18735768
TI  - LYMPHOSARCOMA OF THE SUPERIOR MEDIASTINUM.

PMID- 18735767
TI  - CHILBLAINS.

PMID- 18735769
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18735771
TI  - MUSCLE CHANGES IN TUBERCULOSIS.

PMID- 18735770
TI  - STATEMENT OF THE OWNERSHIP, MANAGEMENT, CIRCULATION, ETC.

PMID- 18735772
TI  - SOCIETY REPORTS.

PMID- 18735773
TI  - UTAH AND NEVADA ADOPT RESOLUTIONS.

PMID- 18735774
TI  - A RESTRICTED MATERIA MEDICA.

PMID- 18735775
TI  - TREATMENT OF FRACTURES.

PMID- 18735776
TI  - INCONCEIVABLE IGNORANCE.

PMID- 18735777
TI  - THE FIRST EXPEDITION FROM THE TULANE UNIVERSITY SCHOOL OF TROPICAL MEDICINE TO
      THE TROPICS FOR THE STUDY OF MALARIA.

PMID- 18735778
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18735780
TI  - A NEW YEAR; A NEW VOLUME.

PMID- 18735779
TI  - PROPER RECIPROCITY.

PMID- 18735781
TI  - Urinary Tract Infections in Women.

PMID- 18735782
TI  - Gastrotomy With Removal of 1149 Foreign Bodies. Recovery.

PMID- 18735783
TI  - Milk Supply of San Francisco and Its Bacterial Content.

PMID- 18735784
TI  - Post Operative Acidosis.

PMID- 18735785
TI  - A New Year's Greeting.

PMID- 18735786
TI  - The Importance of Non-Diabetic Acidosis.

PMID- 18735787
TI  - Transfusion.

PMID- 18735788
TI  - EPIDEMIC POLIOMYELITIS.

PMID- 18735790
TI  - CONGRESSES AND CLINICS.

PMID- 18735789
TI  - THE DIAGNOSIS OF TUBERCULOSIS OF THE SKIN.

PMID- 18735792
TI  - THAW AND SCHRANK.

PMID- 18735791
TI  - PROGRESS IN ANESTHESIA.

PMID- 18735793
TI  - SOCIETY REPORTS.

PMID- 18735794
TI  - APPRECIATION OF THE TELEPHONE.

PMID- 18735796
TI  - ARMY MEDICAL CORPS EXAMINATIONS.

PMID- 18735795
TI  - SANITARY SCIENCE AT TULANE UNIVERSITY, NEW ORLEANS, LA.

PMID- 18735797
TI  - OUR MEDICAL DEFENSE.

PMID- 18735798
TI  - IMPROVEMENTS IN THE NATIONAL PARKS IN CALIFORNIA.

PMID- 18735799
TI  - TRAVEL STUDY TOUR.

PMID- 18735800
TI  - LATIN-AMERICAN MEDICAL CONGRESS AND EXPOSITION OF HYGIENE.

PMID- 18735801
TI  - PASTERS WORK.

PMID- 18735803
TI  - MEDICAL BUILDINGS.

PMID- 18735802
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18735804
TI  - SUICIDAL CONTRACT PRACTICE.

PMID- 18735805
TI  - EDDYITE CONTRADICTIONS.

PMID- 18735807
TI  - DECEMBER EXAMINATION.

PMID- 18735806
TI  - BOHANON AMENDMENT UNCONSTITUTIONAL.

PMID- 18735809
TI  - EDUCATIONAL ASSISTANCE.

PMID- 18735808
TI  - THE NEXT ANNUAL MEETING.

PMID- 18735810
TI  - WIDELY DISTRIBUTED INTEREST.

PMID- 18735811
TI  - On the Tolerance of the Vitreous to Dislocated Lenses.

PMID- 18735812
TI  - Neuroses of the Mouth and Throat.

PMID- 18735813
TI  - THE LEGISLATURE.

PMID- 18735814
TI  - UNPLEASANT PUBLICITY.

PMID- 18735815
TI  - A VALUABLE (?) PUBLICATION.

PMID- 18735816
TI  - PROSECUTING ILLEGAL PRACTITIONERS.

PMID- 18735817
TI  - LACK OF COORDINATION.

PMID- 18735818
TI  - CONGRESS FOR PHYSIOTHERAPY.

PMID- 18735820
TI  - LODGE AND CONTRACT DOCTORS BARRED.

PMID- 18735819
TI  - NEW SOCIETY; OLD JOB.

PMID- 18735821
TI  - MEDICAL BUILDING.

PMID- 18735822
TI  - GOING TO BUY AN AUTOMOBILE?

PMID- 18735823
TI  - THE OAKLAND MEETING.

PMID- 18735825
TI  - DUES! DUES! DUES!

PMID- 18735824
TI  - BOARD OF CONTROL REPORT.

PMID- 18735826
TI  - FRAUDULENT DISINFECTANTS.

PMID- 18735827
TI  - Tonsils and Adenoids.

PMID- 18735829
TI  - Some Factors in Habitual Constipation.

PMID- 18735828
TI  - Operative Treatment for Tic Douloureaux of the Inferior Dental Nerve.

PMID- 18735830
TI  - Feeding in Later Infancy.

PMID- 18735831
TI  - Dietetics From a Modern Standpoint.

PMID- 18735832
TI  - Recent Case of Lipectomy.

PMID- 18735833
TI  - Report of Case of Double Tubal Pregnancy.

PMID- 18735834
TI  - The Technic of the Removal of Foreign Bodies.

PMID- 18735835
TI  - Prophylactic Measures for People Growing Blind.

PMID- 18735837
TI  - PRESIDENT'S ADDRESS.

PMID- 18735836
TI  - Gasserectomy. (Report of three cases.).

PMID- 18735838
TI  - THE TREATMENT OF SURGICAL SHOCK.

PMID- 18735840
TI  - SOCIETY REPORTS.

PMID- 18735839
TI  - TUBERCULOSIS AMONG RAILROAD EMPLOYEES.

PMID- 18735841
TI  - HENRY SAYRE ORME, M. D.

PMID- 18735842
TI  - DR. BEVERLEY MACMONAGLE.

PMID- 18735843
TI  - DR. JAMES B. HANNAH.

PMID- 18735845
TI  - RESOLUTIONS ON THE DEATH OF DR. GEO. S. BAKER.

PMID- 18735844
TI  - DR. EMIL STELTZNER.

PMID- 18735847
TI  - AN INTERESTING CIRCULAR.

PMID- 18735846
TI  - TWO YEARS' INTERNESHIP-GOOD SAMARITAN HOSPITAL, GUANAJUATO, MEXICO.

PMID- 18735848
TI  - REPORT ON CONDITION OF ACCOUNTS OF STATE BOARD OF HEALTH.

PMID- 18735849
TI  - Report Covering Affairs of State Board of Medical Examiners and Supplementary
      Report.

PMID- 18735850
TI  - Supplemental Report.

PMID- 18735851
TI  - LANE MEDICAL LIBRARY: Announcement of Hours.

PMID- 18735853
TI  - EQUAL OPPORTUNITY AND THE SQUARE DEAL.

PMID- 18735852
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18735854
TI  - WHEN IS A CURE NOT A CURE?

PMID- 18735855
TI  - MEDICAL EDUCATION IN EUROPE.

PMID- 18735856
TI  - THE EDUCATIONAL VALUE OF MOVING PICTURES.

PMID- 18735857
TI  - Successful Removal of an Intradural Tumor from the Spinal Canal.

PMID- 18735858
TI  - The Variations of the Clinical Picture of Meningeal Affection.

PMID- 18735859
TI  - Two Cases of Appendicitis With Certain Post-Operative Complications.

PMID- 18735860
TI  - Chinese Medicine in America.

PMID- 18735862
TI  - Hookworm Disease and Its Importation into California.

PMID- 18735861
TI  - Sarcoma of the Uterus.

PMID- 18735863
TI  - Some Observations on Symptoms and Treatment of Suppurative Appendicitis.

PMID- 18735864
TI  - SOCIETY REPORTS.

PMID- 18735865
TI  - DR. J. S. POTTS: Died February 9, 1913.

PMID- 18735867
TI  - AN ENCOURAGING CASE.

PMID- 18735866
TI  - AN APPRECIATION.

PMID- 18735868
TI  - DR. FRIEDMANN'S TUBERCULOSIS REMEDY.

PMID- 18735870
TI  - DIABETES-MELLITUS.

PMID- 18735869
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18735871
TI  - MEDICAL DEFENSE NOTES.

PMID- 18735872
TI  - IMPORTANT SUIT WON.

PMID- 18735873
TI  - DID NOT UNDERSTAND.

PMID- 18735874
TI  - DISCOURAGING WORK.

PMID- 18735876
TI  - ALL'S WELL, THAT ENDS WELL.

PMID- 18735875
TI  - CHINESE MEDICINE.

PMID- 18735877
TI  - MEDICAL BILLS IN THE LEGISLATURE.

PMID- 18735878
TI  - OPHTHALMOLOGICAL CONGRESS.

PMID- 18735879
TI  - REPORTING COMMUNICABLE DISEASES.

PMID- 18735880
TI  - MISPLACED CONFIDENCE.

PMID- 18735881
TI  - PROMOTING FAKES.

PMID- 18735882
TI  - WHY NOT MORE SUCH MEETINGS?

PMID- 18735883
TI  - DANGEROUS PHYLACOGENS.

PMID- 18735884
TI  - LEHN & FINK; A PROTEST.

PMID- 18735885
TI  - LOST ARTS.

PMID- 18735886
TI  - POSSIBLE-BUT-?

PMID- 18735887
TI  - TUBERCULOSIS OF BONES AND JOINTS.

PMID- 18735888
TI  - DOCTORS AND LAWYERS.

PMID- 18735889
TI  - Rational Psychotherapy.

PMID- 18735890
TI  - Psychotherapy in Sexual Neurasthenia.

PMID- 18735891
TI  - Psychiatric Duties of Large Cities.

PMID- 18735892
TI  - Are We Doing as Much for the Tuberculosis Patient as We Should?

PMID- 18735894
TI  - Prospects and Retrospects.

PMID- 18735893
TI  - Inter-Auricular or Inter-Ventricular Deficiency of Septum?

PMID- 18735895
TI  - Granuloma Inguinale Tropicum.

PMID- 18735896
TI  - The Occipito-Posterior Position.

PMID- 18735897
TI  - Some Conclusions Regarding the Present Knowledge of Vermiform Appendix.

PMID- 18735899
TI  - SOCIETY REPORTS.

PMID- 18735898
TI  - TREATMENT OF FRACTURES OF PATELLA.

PMID- 18735901
TI  - JOHN M. LACY, M. D.

PMID- 18735900
TI  - INFLUENZAL MENINGITIS SERUM.

PMID- 18735903
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18735902
TI  - DR. HUGH CROSS.

PMID- 18735904
TI  - WHO ARE YOUR FRIENDS?

PMID- 18735905
TI  - PHYLACOGENS, THE JOURNAL A. M. A., AND PARKE, DAVIS & CO.

PMID- 18735906
TI  - DISASTER BY WIND AND FLOOD.

PMID- 18735908
TI  - A MOST VALUABLE BOOK.

PMID- 18735907
TI  - MECHANIC OR MEDIC?

PMID- 18735909
TI  - THE ANNUAL MEETING AT OAKLAND.

PMID- 18735910
TI  - ON A NEW KIND OF SURGICAL LITERATURE.

PMID- 18735912
TI  - THE AMERICAN ROYAL COLLEGE OF SURGEONS-J. B. M.

PMID- 18735911
TI  - THE COST OF LIVING; THEN AND NOW.

PMID- 18735913
TI  - RESOLUTIONS ON CONTRACT PRACTICE.

PMID- 18735914
TI  - WASSERMANN'S AND WASSERMANN'S.

PMID- 18735915
TI  - IMPROVING MEDICAL EDUCATION IN THE UNITED STATES.

PMID- 18735916
TI  - Summer Diarrhea from the Standpoint of the Clinician.

PMID- 18735917
TI  - On the Relation of the Academic Medical School to the Medical Community.

PMID- 18735918
TI  - Treatment of the Spiral Fractures of the Tibia.

PMID- 18735919
TI  - A Physician's Vacation.

PMID- 18735920
TI  - Acute Poliomyelitis in California.

PMID- 18735921
TI  - Impressions.

PMID- 18735922
TI  - Staphyloccus Spray for Diphtheria Carriers.

PMID- 18735923
TI  - Psychiatric Duties of Large Cities.

PMID- 18735924
TI  - Report of a Case of Sarcomatosis.

PMID- 18735925
TI  - A FEW REMARKS ON THE MANAGEMENT OF TYPHOID.

PMID- 18735927
TI  - HOW GENEROUS!

PMID- 18735926
TI  - SOCIETY REPORTS.

PMID- 18735928
TI  - INSTRUCTOR FOR MIRAJ MEDICAL SCHOOL.

PMID- 18735929
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18735930
TI  - LEGISLATIVE ENACTMENTS.

PMID- 18735931
TI  - PERSONAL MENTION.

PMID- 18735933
TI  - THE FRIEDMANN-PIORKOWSKY-HEID MESS.

PMID- 18735932
TI  - NEW STATE INSANE ASYLUM.

PMID- 18735934
TI  - THE MERMAIDS AND NEPTUNES.

PMID- 18735935
TI  - THE AMERICAN ROYAL SURGICAL EMPORIUM.

PMID- 18735937
TI  - AMERICAN MEDICAL ASSOCIATION MEETING.

PMID- 18735936
TI  - WHAT'S THE USE?

PMID- 18735938
TI  - LACK OF SUPPORT.

PMID- 18735939
TI  - "CHIROPRACTIC" MODESTY.

PMID- 18735940
TI  - THE TEA BEE.

PMID- 18735941
TI  - INSURANCE COMPANIES' LIES.

PMID- 18735942
TI  - WASSERMANN REACTIONS.

PMID- 18735943
TI  - A PHYSICIANS' TELEPHONE EXCHANGE.

PMID- 18735944
TI  - EDITORIAL POLICY NOT ENDORSED.

PMID- 18735946
TI  - President's Address.

PMID- 18735945
TI  - Oliver D. Hamlin, M. D.

PMID- 18735947
TI  - Report of the Secretary and Editor.

PMID- 18735948
TI  - REPORT OF THE COUNCIL.

PMID- 18735949
TI  - Report of the California State Tuberculosis Commission.

PMID- 18735950
TI  - Report of Special Committee on the Effect of Athletics on Young People.

PMID- 18735951
TI  - Effects of Athletics on Young People.

PMID- 18735952
TI  - Thoracic Esophagectomy: Report of a Case.

PMID- 18735953
TI  - Suggestions for a Mental Hygiene.

PMID- 18735954
TI  - Present Status of Prostatic Surgery.

PMID- 18735955
TI  - The Lingual Tonsil and Some of Its Diseases.

PMID- 18735956
TI  - The Absence of Brain Tumor Symptoms in Cases of Tumors of the Brain.

PMID- 18735957
TI  - AN INSTANCE OF HYPERSENSITIVENESS TO HOMATROPIN.

PMID- 18735958
TI  - RAYNAUD'S DISEASE-REPORT OF A CASE.

PMID- 18735959
TI  - SUBLIMATE POISONING; A CASE REPORT.

PMID- 18735960
TI  - INTRODUCED BY SENATOR AVEY. January 27, 1913: Referred to Committee on Public
      Health and Quarantine.

PMID- 18735961
TI  - A CASE OF ANGIONEUROTIC EDEMA CURED BY INJECTIONS OF HORSE SERUM.

PMID- 18735962
TI  - SOCIETY REPORTS.

PMID- 18735963
TI  - ARMY MEDICAL CORPS EXAMINATIONS.

PMID- 18735964
TI  - HEALTH DIRECTOR WANTED.

PMID- 18735966
TI  - SOME INTERESTING FIGURES.

PMID- 18735965
TI  - WILL STAND WATCHING.

PMID- 18735968
TI  - INFANT MORTALITY.

PMID- 18735967
TI  - NEW AND NONOFFICIAL REMEDIES.

PMID- 18735969
TI  - STATEMENT OF THE OWNERSHIP, MANAGEMENT, CIRCULATION, ETC.

PMID- 18735970
TI  - LAWYERS' AND DOCTORS' FEES.

PMID- 18735971
TI  - INHUMAN COMEDY.

PMID- 18735972
TI  - TELEPHONE EXCHANGE; AN ERROR CORRECTED.

PMID- 18735974
TI  - DIVISION OF FEES; THE LOS ANGELES TREATMENT.

PMID- 18735973
TI  - DISHONEST BUSINESS BY MEDICAL (?) JOURNALS.

PMID- 18735975
TI  - THE COLLEGE.

PMID- 18735976
TI  - Intratracheal Insufflation Anesthesia.

PMID- 18735977
TI  - Recurrence of Hydrocele After Radical Treatment.

PMID- 18735978
TI  - The Nature of Disease.

PMID- 18735979
TI  - The Medical Treatment of Gall-Bladder Disease.

PMID- 18735980
TI  - The Treatment of Tuberculosis With a Soluble Vaccine.

PMID- 18735982
TI  - Why Does Cancer Attack the Face?

PMID- 18735981
TI  - Medical Endowment for the University of California.

PMID- 18735983
TI  - Evolution in the Study of the Heart: A Survey.

PMID- 18735984
TI  - Stereo-Roentgenography in Pulmonary Tuberculosis: A Clinical and Anatomical
      Study.

PMID- 18735985
TI  - Two Cases of Cerebellar Disease Followed by Autopsy.

PMID- 18735986
TI  - FACTORS IN THE PHYSIOLOGY OF BONE IN RELATION TO SURGERY.

PMID- 18735987
TI  - THE ARNETH BLOOD COUNT IN PULMONARY TUBERCULOSIS-A REPORT OF 80 CASES.

PMID- 18735988
TI  - ON THE DIFFERENTIAL DIAGNOSIS OF APPENDICITIS AND NEPHROLITHIASIS.

PMID- 18735989
TI  - THE SKIN REACTION AFTER COWPOX VACCINATION. A POSSIBLE AID IN PUBLIC HEALTH
      ADMINISTRATION.

PMID- 18735990
TI  - CHRONIC DISEASE OF THE GALL-BLADDER AND APPENDIX AS ETIOLOGIC FACTORS IN THE
      PRODUCTION OF DIGESTIVE SYMPTOMS.

PMID- 18735992
TI  - SOCIETY REPORT.

PMID- 18735991
TI  - STATE CARE FOR CRIPPLED CHILDREN IN CALIFORNIA.

PMID- 18735993
TI  - TO OUR ADVERTISERS.

PMID- 18735994
TI  - NO MEDICAL SCHOOLS.

PMID- 18735995
TI  - THE MINNEAPOLIS MEETING.

PMID- 18735996
TI  - DRUGGISTS' BREACH OF FAITH.

PMID- 18735997
TI  - SHALL WE BE SILENT?

PMID- 18735999
TI  - THE NEW LAW.

PMID- 18735998
TI  - ETHICAL PROPRIETARY AND "PATENT MEDICINE," ALL IN ONE.

PMID- 18736001
TI  - THE COLLEGE.

PMID- 18736000
TI  - PAID LOBBY REJECTED!

PMID- 18736002
TI  - PREACHING ADVERTISING HONESTY.

PMID- 18736003
TI  - Gall-Tract Disease-Some Clinical Features Frequently Overlooked in Its Diagnosis.

PMID- 18736004
TI  - Surgical Treatment of Gall-Bladder Disease.

PMID- 18736005
TI  - The Symptomatology of Gall-Bladder Disease.

PMID- 18736006
TI  - Cholelithiasis With A Short Review of One Hundred Necropsies.

PMID- 18736007
TI  - SYMPOSIUM ON GALL-BLADDER: Discussion.

PMID- 18736009
TI  - Comments on Tuberculin.

PMID- 18736008
TI  - The Work of the Pasteur Division of the State Hygienic Laboratory.

PMID- 18736011
TI  - Bacteriology of the Urine in Relation to Movable Kidney.

PMID- 18736010
TI  - The Intravenous Administration of Diphtheria Antitoxin.

PMID- 18736012
TI  - Carbohydrate Cures in Diabetes.

PMID- 18736014
TI  - CONTACT WITH STILL HIGHER TENSION CURRENT.

PMID- 18736013
TI  - THE EFFECT OF A MOMENTARY CONTACT WITH AN 18,000 VOLT CURRENT.

PMID- 18736015
TI  - SOCIETY REPORT.

PMID- 18736016
TI  - PHYSICIANS' COLLECTION GUIDE.

PMID- 18736017
TI  - LANE LECTURES.

PMID- 18736018
TI  - AMERICAN ASSOCIATION FOR CANCER RESEARCH.

PMID- 18736019
TI  - INTERESTING REPORTS.

PMID- 18736020
TI  - BOOK PUBLISHERS IN SAN FRANCISCO.

PMID- 18736021
TI  - NEW AND NONOFFICIAL REMEDIES.

PMID- 18736022
TI  - POLITICS.

PMID- 18736024
TI  - THE WRITING ON THE WALL.

PMID- 18736023
TI  - REPORTING ACCIDENTS.

PMID- 18736025
TI  - RATHER ENCOURAGING.

PMID- 18736027
TI  - Experience with Artificial Pneumothorax in the Treatment of Pulmonary
      Tuberculosis: Part I.

PMID- 18736026
TI  - SHOOTING AT STRAWS.

PMID- 18736028
TI  - Effects of and Indications for Artificial Pneumothorax in the Treatment of
      Pulmonary Tuberculosis: Part II.

PMID- 18736029
TI  - Primary Infection with Tuberculosis Bacilli, with Special Reference to Thoracic
      Glands.

PMID- 18736030
TI  - Management of Fractured Charcot Hip Joint.

PMID- 18736032
TI  - Modern Therapy of Syphilis.

PMID- 18736031
TI  - The Meniere Symptom-Complex. A Clinical Review.

PMID- 18736033
TI  - Luetin as an Aid in the Diagnosis of Syphilis.

PMID- 18736034
TI  - Chronic Intestinal Amebiasis, Without Dysentery: Report of Two Cases.

PMID- 18736035
TI  - The Cutaneous Reaction of Syphilis-(Luetin Reaction): Third Communication.

PMID- 18736037
TI  - ORTHOPEDIC TREATMENT OF SPINAL POLIOMYELITIS.

PMID- 18736036
TI  - Entero-Clysis in the Treatment of Weak Hearts.

PMID- 18736038
TI  - A REVIEW OF BLOOD CHANGES THAT MAY ASSIST IN THE DIAGNOSIS OF CANCER.

PMID- 18736039
TI  - SOCIETY REPORT.

PMID- 18736040
TI  - LANE LECTURES.

PMID- 18736041
TI  - PACIFIC COAST OTO-OPTHALMOLOGICAL SOCIETY.

PMID- 18736042
TI  - DISAPPROVAL.

PMID- 18736043
TI  - NEW AND NONOFFICIAL REMEDIES.

PMID- 18736044
TI  - FREE BEDS.

PMID- 18736045
TI  - LABOR AND "PATENT MEDICINES.".

PMID- 18736046
TI  - A CONSIDERABLE MESS.

PMID- 18736047
TI  - PLAGUE IN SQUIRRELS; AND RABIES.

PMID- 18736048
TI  - IS THE CLINICAL CONGRESS AN UNMIXED BLESSING?

PMID- 18736049
TI  - FRIEDMANN AND THE PRESS.

PMID- 18736051
TI  - POETIC RECOGNITION.

PMID- 18736050
TI  - THE RISE OF THE OSTEOPATH.

PMID- 18736053
TI  - THE HEALTH HOSPITAL ASSOCIATION.

PMID- 18736052
TI  - CONCERNING COURTESY.

PMID- 18736055
TI  - The Effect of Competitive Athletics on Scholarship.

PMID- 18736054
TI  - Dermatological Case Reports.

PMID- 18736056
TI  - Sclero-Corneal Trephining for Glaucoma.

PMID- 18736058
TI  - Treatment of Urinary Tuberculosis, Tuberculin and Nephrectomy.

PMID- 18736057
TI  - Use of Sera in Medical Hemorrhage.

PMID- 18736060
TI  - Address on the Social Evil.

PMID- 18736059
TI  - Report on Four Cases of Varying Types of Anemia.

PMID- 18736061
TI  - Report of a Case of Rabies in Which a Child Bit Her Father.

PMID- 18736062
TI  - Hema-Uro-Chrome. A New Laboratory Test for Cancer and Sarcoma; from the Urine.

PMID- 18736063
TI  - Physicians' Aspect of Sunday Closing of Pharmacies.

PMID- 18736064
TI  - ATROPHY OF THE PROSTATE GLAND WITH CITATION OF CASES.

PMID- 18736066
TI  - THE UNDESCENDED TESTICLE: REPORT OF TWO CASES.

PMID- 18736065
TI  - TRAUMATIC HYSTERIA.

PMID- 18736067
TI  - INTENSIVE STRYCHNIN TREATMENT OF TRIFACIAL NEURALGIA.

PMID- 18736068
TI  - ORTHOPEDIC TREATMENT OF SPINAL POLIOMYELITIS.

PMID- 18736069
TI  - PELLAGRA.

PMID- 18736071
TI  - FRAUDULENT RADIOACTIVE WATERS.

PMID- 18736070
TI  - SOCIETY REPORT.

PMID- 18736073
TI  - FORM OF DECLARATION REQUIRED OF IMPORTERS OF COCAINE.

PMID- 18736072
TI  - SCHOOL FOR HEALTH OFFICERS.

PMID- 18736075
TI  - THE SAN FRANCISCO POLYCLINIC AND THE SAN FRANCISCO COLLEGE OF MEDICINE COMBINED.

PMID- 18736074
TI  - NEW AND NONOFFICIAL REMEDIES.

PMID- 18736077
TI  - OF UTMOST IMPORTANCE!

PMID- 18736076
TI  - PUBLIC HEALTH.

PMID- 18736078
TI  - WHERE DOES THE "PHYSICIAN" COME IN?

PMID- 18736079
TI  - WHAT NOW?

PMID- 18736080
TI  - UNIFORM MEMBERSHIP.

PMID- 18736081
TI  - DAMAGED GOODS-AND FOLLY.

PMID- 18736082
TI  - BOARD OF MEDICAL EXAMINERS.

PMID- 18736084
TI  - GOING TO BUY ANYTHING?

PMID- 18736083
TI  - CLINICAL CONGRESS.

PMID- 18736085
TI  - Value of Pyelography for the Diagnosis of Hydronephrosis.

PMID- 18736086
TI  - Exophthalmic Goiter: Indications and Contraindications to Operations.

PMID- 18736087
TI  - Clinical Methods of Estimating the Degree of Acidosis.

PMID- 18736088
TI  - Early Symptoms of Poliomyelitis with Special Reference to a New Preparalytic
      Symptom.

PMID- 18736089
TI  - The Effects of Civilization Upon Our Eyes.

PMID- 18736091
TI  - X-Ray Findings Along the Gastro Intestinal Tract.

PMID- 18736090
TI  - Partial Bilateral Nephrectomy in a Case of Calculous Pyonephrosis.

PMID- 18736092
TI  - Affections of the Eyes Resulting From Sinus Involvements.

PMID- 18736093
TI  - Ringworm in California.

PMID- 18736094
TI  - An Unusual Case of Ophthalmic Migraine.

PMID- 18736095
TI  - FOUR CASES OF REMOVAL OF A PREFRONTAL TUMOR OF THE BRAIN.

PMID- 18736096
TI  - THE DIFFERENTIAL DIAGNOSIS OF PALMAR SYPHILIS, ECZEMA AND PSORIASIS.

PMID- 18736097
TI  - PARASITIC SKIN DISEASE IN CALIFORNIA.

PMID- 18736098
TI  - THROMBOSIS OF THE LATERAL SINUS WITH REPORT OF FIVE CASES.

PMID- 18736099
TI  - THREE CASES OF PELLAGRA IN SAN FRANCISCO.

PMID- 18736100
TI  - DUCTLESS GLAND EXTRACTS IN RELATION TO EAR AFFECTIONS.

PMID- 18736102
TI  - FLEXNER'S MENINGITIS SERUM.

PMID- 18736101
TI  - SOCIETY REPORT.

PMID- 18736103
TI  - BUBONIC PLAGUE; ANOTHER HUMAN CASE.

PMID- 18736104
TI  - ORANGE COUNTY'S NEW HOSPITAL.

PMID- 18736106
TI  - YE HUMOURS OF YE BLOOD.

PMID- 18736105
TI  - NEW AND NONOFFICIAL REMEDIES.

PMID- 18736107
TI  - THE SECOND DECADE.

PMID- 18736108
TI  - AMENDMENT TO THE CONSTITUTION.

PMID- 18736110
TI  - OUR CRITICS.

PMID- 18736109
TI  - GOOD TREATMENT FOR INSURANCE COMPANY.

PMID- 18736112
TI  - A SAMPLE LETTER.

PMID- 18736111
TI  - HOW FAR SHALL PROTECTION GO?

PMID- 18736113
TI  - THE INJECTION OF CONCENTRATED SOLUTIONS OF 606 AND 914.

PMID- 18736114
TI  - AN INFLUX.

PMID- 18736115
TI  - PUBLIC HEALTH NUMBER.

PMID- 18736117
TI  - The Ideal Hospital.

PMID- 18736116
TI  - The Debt of Human Embryology to the Practitioner.

PMID- 18736118
TI  - Implantation of Joints.

PMID- 18736120
TI  - How to Read the Pneumonothorax Manometer.

PMID- 18736119
TI  - Toxic Effects of Salvarsan.

PMID- 18736122
TI  - Auricular Fibrillation.

PMID- 18736121
TI  - Iritis; Some Facts of General Interest.

PMID- 18736123
TI  - The Futility of Cardiac Stimulants in Shock.

PMID- 18736124
TI  - TRAUMATIC RETROPERITONEAL DISPLACEMENT OF THE DUODENUM; ABSOLUTE OBSTRUCTION
      DEVELOPING GRADUALLY THEREFROM; GASTRO-JEJUNOSTOMY; DUODENUM-JEJUNOSTOMY;
      RECOVERY.

PMID- 18736125
TI  - SOCIETY REPORT.

PMID- 18736126
TI  - ANNOUNCEMENT OF THE LANE MEDICAL LIBRARY.

PMID- 18736127
TI  - LAY RECOGNITION.

PMID- 18736128
TI  - UNION HEALTH DEPARTMENTS.

PMID- 18736129
TI  - NEW YEAR-NEW OPPORTUNITIES.

PMID- 18736130
TI  - The Relation of the Sanitarium to Vocational Guidance.

PMID- 18736132
TI  - Suggested Improvements in Our Methods of Controlling the Common Contagious
      Diseases.

PMID- 18736131
TI  - Modification in Administrative Measures Necessitated by the Carrier Problem.

PMID- 18736134
TI  - Regulations of the California State Board of Health: For the Enforcement of An
      Act to Prevent the Introduction and Spread of Rabies.

PMID- 18736133
TI  - Recent Legislation on Communicable Diseases in the United States.

PMID- 18736136
TI  - PUBLIC HEALTH AND INTERFERENCE.

PMID- 18736135
TI  - CIVIL SERVICE AND PUBLIC HEALTH.

PMID- 18736137
TI  - EMINENT MEDICAL AUTHORITY.

PMID- 18736139
TI  - Rating the Efficiency of Hospitals and Institutions for the Tuberculous.

PMID- 18736138
TI  - Administrative Measures for the Control of Scarlet Fever.

PMID- 18736141
TI  - The Fifth Annual Conference of State, County and Municipal Health Officials.

PMID- 18736140
TI  - The Venereal Disease Problem.

PMID- 18736142
TI  - PELLAGRA.

PMID- 18736143
TI  - "SQUEEZE THE DOCTOR" AGAIN!

PMID- 18736144
TI  - SCHOOL OF HYGIENE AND SANITATION.

PMID- 18736146
TI  - BRIEF NOTES ON THE FORMATION AND ORTHOGRAPHY AND PRONUNCIATION OF MEDICAL TERMS.

PMID- 18736145
TI  - VERY IMPORTANT TO YOU!

PMID- 18736147
TI  - ARTIFICIAL SYNOSTOSIS OF THE TUBERCULOUS SPINE.

PMID- 18736148
TI  - RECENT ADVANCES IN THE TREATMENT OF DACRYOSTENOSIS.

PMID- 18736149
TI  - SOCIETY REPORT.

PMID- 18736151
TI  - ARMY MEDICAL CORPS EXAMINATIONS.

PMID- 18736150
TI  - LOOK OUT FOR THIS MAN.

PMID- 18736153
TI  - NEW AND NONOFFICIAL REMEDIES.

PMID- 18736152
TI  - UNUSUALLY LARGE BABY.

PMID- 18736154
TI  - USE OF HEROIN SPREADING RAPIDLY AMONG DRUG FIENDS.

PMID- 18736156
TI  - Points Regarding Tuberculosis of Interest to Health Officers.

PMID- 18736155
TI  - Rabies in San Francisco, With Notes on Some Recent Additions to Our Knowledge of
      the Disease.

PMID- 18736158
TI  - SUITS FOR DAMAGES AND THEIR DEFENSE.

PMID- 18736157
TI  - WHY NOT SAVE THE MONEY?

PMID- 18736160
TI  - A SUGGESTION FOR HELP.

PMID- 18736159
TI  - A NEW MEDICAL (?) ORGAN FOR "SLAMMING.".

PMID- 18736162
TI  - SOCIAL FERMENT.

PMID- 18736161
TI  - THE COSTUME OF "THE COLLEGE.".

PMID- 18736163
TI  - Where Does the Doctor Come In?

PMID- 18736164
TI  - The Industrial Compensation Act.

PMID- 18736165
TI  - Industrial Accident Law.

PMID- 18736166
TI  - A Plea for the Immediate Operation of Fractures.

PMID- 18736167
TI  - A New Treatment of Poliomyelitis.

PMID- 18736168
TI  - Surgical Complications, Treatment and Preventions.

PMID- 18736169
TI  - Presentation of Patients: Congenital Dislocation of the Hip and Extensive
      Skeletal Tuberculosis. Radiogram.

PMID- 18736170
TI  - CARCINOMA OF THE RECTUM REMOVED FOUR AND A HALF YEARS AGO; HYPERTROPHIED PROSTATE
      RECENTLY REMOVED FROM THE SAME PATIENT. METHOD OF AFTER-TREATMENT OF ENUCLEATION
      OF THE PROSTATE.

PMID- 18736172
TI  - The Epidemiology and Control of Rabies.

PMID- 18736171
TI  - A CASE OF LUDWIG'S ANGINA.

PMID- 18736173
TI  - A Positive Reading Manometer for Therapeutic Pneumo-Thorax.

PMID- 18736175
TI  - PRESIDENTIAL ADDRESS.

PMID- 18736174
TI  - LOS ANGELES COUNTY MEDICAL ASSOCIATION.

PMID- 18736176
TI  - REPORT OF SECRETARY.

PMID- 18736177
TI  - REPORT OF THE LIBRARIAN.

PMID- 18736178
TI  - REPORT OF THE MILK COMMISSION.

PMID- 18736179
TI  - SOCIETY REPORT.

PMID- 18736180
TI  - MEDICAL FEE SCHEDULE.

PMID- 18736181
TI  - TRAINING IN HOME ECONOMICS.

PMID- 18736182
TI  - BOUILLON CUBES NOT CONCENTRATED MEAT ESSENCE.

PMID- 18736184
TI  - INTERESTING FRAUDS.

PMID- 18736183
TI  - REPORT TUBERCULOSIS.

PMID- 18736185
TI  - A Case of Hemoglobinuric Fever.

PMID- 18736186
TI  - Madelung's Deformity.

PMID- 18736187
TI  - Closure of the Abdomen in the Face of Sepsis. Report of One Hundred Consecutive
      Cases.

PMID- 18736189
TI  - Vaccination Against Tuberculosis With Von Ruck Vaccine.

PMID- 18736188
TI  - Intratracheal Anesthesia.

PMID- 18736190
TI  - TREATMENT OF GONORRHEA IN THE FEMALE.

PMID- 18736192
TI  - PERSISTENT CONJUNCTIVAL HYPERAEMIA AFTER CATARACT EXTRACTION AND ITS CAUSE-REPORT
      OF SIX CASES ILLUSTRATING THIS CONDITION.

PMID- 18736191
TI  - ROENTGEN-RAYS AND MESOTHORIUM IN GYNECOLOGIC PRACTICE: REPORT ON THEIR
      APPLICATION AT SEVERAL GERMAN UNIVERSITY CLINICS FROM PERSONAL OBSERVATION.

PMID- 18736193
TI  - NOTE ON THE SATURATION-POINT OF SERUM FOR NORMAL LIPOIDS AND CHOLESTERIN.

PMID- 18736195
TI  - A CASE OF VERONAL POISONING.

PMID- 18736194
TI  - REPORT OF A CASE OF SYSTEMIC BLASTOMYCOSIS.

PMID- 18736197
TI  - RESOLUTIONS ADOPTED BY LOS ANGELES: 1. RESOLUTIONS IN REGARD TO FEE TABLES OF
      WORKINGMEN'S COMPENSATION ACT.

PMID- 18736196
TI  - SOCIETY REPORT: PROCEEDINGS OF THE SAN FRANCISCO COUNTY MEDICAL SOCIETY.

PMID- 18736198
TI  - MEDICAL CONTRACTING BY WHOLESALE.

PMID- 18736199
TI  - THE LATE E. L. B. GODFREY, M. D.

PMID- 18736200
TI  - A SUGGESTION ABOUT FEES.

PMID- 18736201
TI  - SQUEEZING THE COMPANIES.

PMID- 18736202
TI  - WHAT IS THE VALUE OF ANYTHING?

PMID- 18736203
TI  - WHISPER HIM TO DEATH.

PMID- 18736204
TI  - IMPORTANT BUSINESS.

PMID- 18736205
TI  - TUBERCULOSIS; A ROUSING MEETING!

PMID- 18736206
TI  - DISEASE AND ITS CAUSES.

PMID- 18736207
TI  - THE INCOME TAX MUDDLE.

PMID- 18736208
TI  - Some Remarks on the Industrial Insurance Act.

PMID- 18736209
TI  - Remarks on Stone in the Bladder.

PMID- 18736211
TI  - Some Sources of Error in Blood Pressure Measurements.

PMID- 18736210
TI  - Systolic Apical Murmurs.

PMID- 18736212
TI  - OF UTMOST IMPORTANCE TO YOU.

PMID- 18736213
TI  - MEDICAL DEFENSE.

PMID- 18736214
TI  - OUR ONLY HOPE.

PMID- 18736215
TI  - THE ACCIDENT INSURANCE SITUATION.

PMID- 18736217
TI  - PRECIPITATE PUBLICATION.

PMID- 18736216
TI  - ECONOMIC WASTE ON A LARGE SCALE.

PMID- 18736218
TI  - GRATEFUL APPRECIATION.

PMID- 18736219
TI  - CLOSING THE HOSPITAL.

PMID- 18736220
TI  - Tuberculous Glands of the Neck.

PMID- 18736222
TI  - The Therapy of Typhoid Fever-A Critical Review.

PMID- 18736221
TI  - The Psychological Study of Mentally Defective and Otherwise Exceptional Children.

PMID- 18736223
TI  - X-Ray Dosage.

PMID- 18736224
TI  - Vital Statistics.

PMID- 18736225
TI  - The Medical Situation of the New Workmen's Compensation Act.

PMID- 18736227
TI  - Hygienic Shoeing-Anatomical Facts vs. Convention and Style.

PMID- 18736226
TI  - Some Principles Governing the Indications for Caesarean Section.

PMID- 18736229
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736228
TI  - SOCIETY REPORT.

PMID- 18736230
TI  - NEW AND NONOFFICIAL REMEDIES.

PMID- 18736231
TI  - PROPAGANDA FOR REFORM.

PMID- 18736232
TI  - REPORT OF THE BUREAU OF THE HYGIENIC LABORATORY.

PMID- 18736233
TI  - EXTENSION LECTURES FOR COUNTY MEDICAL SOCIETIES.

PMID- 18736234
TI  - ATOPHAN NOT A FRAUD.

PMID- 18736236
TI  - LORD LISTER MEMORIAL.

PMID- 18736235
TI  - LORD LISTER MEMORIAL.

PMID- 18736237
TI  - THE SAN FRANCISCO POLYCLINIC.

PMID- 18736238
TI  - THE SANTA BARBARA MEETING.

PMID- 18736239
TI  - IDEALS.

PMID- 18736241
TI  - ANOTHER EXAMPLE.

PMID- 18736240
TI  - CONSIDER SOME ACTUAL CASES.

PMID- 18736242
TI  - THE FEE SCHEDULE.

PMID- 18736243
TI  - George Chismore.

PMID- 18736244
TI  - THE ANNUAL MEETING AT SANTA BARBARA.

PMID- 18736245
TI  - Early Vaccination Controversy With an Original Letter by Jenner.

PMID- 18736246
TI  - Reminiscences.

PMID- 18736247
TI  - Presentation of Patient Twenty Months After Operation for Uterine Cancer.

PMID- 18736249
TI  - Blindness Following Injuries to the Back of the Head.

PMID- 18736250
TI  - Recollections of the Listerian Epoch.

PMID- 18736248
TI  - The Green Operating Room at St. Luke's Hospital.

PMID- 18736251
TI  - Removal of the Cervical Glands in Malignant Disease of the Head and Face.

PMID- 18736252
TI  - Basic Principles in Eczema.

PMID- 18736253
TI  - A Case of Extraperitoneal, Intraligamentous Dermoid Cyst in Pregnancy.

PMID- 18736254
TI  - Artificial Cultivation of the Gonococcus.

PMID- 18736255
TI  - Upon the Early Diagnosis of Renal Tuberculosis.

PMID- 18736256
TI  - CONCERNING UNUNITED FRACTURES.

PMID- 18736257
TI  - MYXO-LIPOMA OF THE KNEE JOINT.

PMID- 18736259
TI  - IODINE A SPECIFIC GERMICIDE IN RESPIRATORY AFFECTIONS: Preliminary Report.

PMID- 18736258
TI  - ARTIFICIAL PNEUMOTHORAX IN ADVANCED LUNG TUBERCULOSIS.

PMID- 18736260
TI  - HYGIENIC SHOEING-ANATOMICAL FACTS VS. CONVENTION AND STYLE.

PMID- 18736261
TI  - SOCIETY REPORT.

PMID- 18736263
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736262
TI  - DEATHS FOLLOWING INJECTION OF NEOSALVARSAN IN LOS ANGELES.

PMID- 18736264
TI  - SAN FRANCISCO AND THE A. M. A.

PMID- 18736265
TI  - PROCEEDINGS OF THE COUNCIL.

PMID- 18736266
TI  - PROFIT OR LOSS.

PMID- 18736267
TI  - THANKS TO THE STATE SOCIETY.

PMID- 18736268
TI  - COUNTY SOCIETIES; IMPORTANT.

PMID- 18736270
TI  - SCIENTIFIC WORK.

PMID- 18736269
TI  - SURGEON-GENERAL'S LIBRARY.

PMID- 18736272
TI  - TUBERCULOSIS INITIATIVE PETITION.

PMID- 18736271
TI  - PHYSICIANS' STUDY TRAVELS.

PMID- 18736274
TI  - F. C. E. Mattison.

PMID- 18736273
TI  - PUBLIC HEALTH PAMPHLETS.

PMID- 18736275
TI  - Address of the President, Forty-fourth Annual Meeting, Santa Barbara, April,
      1914.

PMID- 18736276
TI  - Report of the Secretary and Editor.

PMID- 18736277
TI  - Twelfth Annual Report of the Council.

PMID- 18736278
TI  - Fee Schedule.

PMID- 18736280
TI  - Concerning Ununited Fractures.

PMID- 18736279
TI  - Report of the Committee on Public Health.

PMID- 18736281
TI  - LASSEN-PLUMAS COUNTIES.

PMID- 18736282
TI  - Report of the Committee on Public Policy and Legislation.

PMID- 18736283
TI  - The Los Angeles Deaths From Intraspinal Neo Salvarsan Injections.

PMID- 18736284
TI  - A Review of the Intercranial Complications.

PMID- 18736285
TI  - SOCIETY REPORT.

PMID- 18736286
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736287
TI  - A CONSERVATION OF VISION CAMPAIGN, WITH A REQUEST FOR CO-OPERATION.

PMID- 18736288
TI  - SALVARSAN IN EROSIVE BALANITIS.

PMID- 18736289
TI  - SUMMER COURSES.

PMID- 18736290
TI  - WARNING TO USERS OF TURPENTINE FOR MEDICINAL OR VETERINARY PURPOSES.

PMID- 18736291
TI  - ELIMINATING THE UNQUALIFIED.

PMID- 18736292
TI  - NO CITY LICENSE FOR PHYSICIANS.

PMID- 18736293
TI  - COUNCIL MEETING.

PMID- 18736294
TI  - A SIGN OF PROGRESS.

PMID- 18736295
TI  - TAKE A VACATION.

PMID- 18736296
TI  - ANOTHER WORD OF APPRECIATION.

PMID- 18736297
TI  - SOME MORE ARGUMENTS.

PMID- 18736298
TI  - GEORGE FREDERICK REINHARDT, M. D.

PMID- 18736299
TI  - Fundamentals in Teaching Sex Hygiene.

PMID- 18736301
TI  - On the Swift-Ellis Treatment of Cerebro-Spinal Syphilis.

PMID- 18736300
TI  - Treatment of General Paralysis of the Insane.

PMID- 18736302
TI  - Prostatic Carcinoma in a Youth.

PMID- 18736303
TI  - The Relation of Localized Tenderness to the Site of the Casual Lesion in
      Perforative Peritonitis.

PMID- 18736304
TI  - The Butyric Acid Test of Noguchi as an Acid in Diagnosis.

PMID- 18736305
TI  - Six Hour Stasis.

PMID- 18736306
TI  - Tabulation and Differential Diagnosis of Liver Cases. Stanford Wards and City and
      County Hospitals.

PMID- 18736307
TI  - Uncomfortable Babies.

PMID- 18736308
TI  - Death Following an Ant Bite.

PMID- 18736309
TI  - Intracranial Pressure.

PMID- 18736311
TI  - A BRIEF SUMMARY OF THE REGISTRATION LAW AND THE REQUIREMENTS FOR ACCREDITING
      SCHOOLS FOR NURSES.

PMID- 18736310
TI  - Echinococcus in California.

PMID- 18736312
TI  - SOCIETY REPORT.

PMID- 18736314
TI  - LUSK ON NUTRITION.

PMID- 18736313
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736316
TI  - RECIPROCATE.

PMID- 18736315
TI  - DIRECTOR CHOSEN FOR HOOPER FOUNDATION.

PMID- 18736317
TI  - CLEANING OUT FRAUDS.

PMID- 18736318
TI  - DR. VAUGHN IN SAN FRANCISCO.

PMID- 18736319
TI  - WORTHY OF PATRONAGE.

PMID- 18736320
TI  - GRADUATE MEDICAL WORK.

PMID- 18736322
TI  - WE STAND BEHIND YOU.

PMID- 18736321
TI  - A. M. A. CHEMICAL LABORATORY REPORTS.

PMID- 18736323
TI  - GUARANTIES AND SERIAL NUMBERS TO END MAY 1, 1915.

PMID- 18736324
TI  - IMPORTANT REQUEST.

PMID- 18736326
TI  - TUBERCULOSIS NUMBER.

PMID- 18736325
TI  - RED CROSS SEALS OR STAMPS.

PMID- 18736328
TI  - TUBERCULOSIS.

PMID- 18736327
TI  - A HELPING HAND.

PMID- 18736329
TI  - ITEMS ABOUT MEDICAL SCHOOLS.

PMID- 18736330
TI  - OFFICERS ELECTED.

PMID- 18736331
TI  - THE ATLANTIC CITY SESSION OF THE A. M. A.

PMID- 18736332
TI  - AMERICAN MEDICAL ASSOCIATION-SAN FRANCISCO, 1915.

PMID- 18736333
TI  - BOARD OF MEDICAL EXAMINERS.

PMID- 18736334
TI  - Address of the President. For the Study and Prevention of Tuberculosis.

PMID- 18736335
TI  - Secretary's Report for the Study and Prevention of Tuberculosis.

PMID- 18736336
TI  - Correspondence.

PMID- 18736337
TI  - Earliest Manifestations of Tuberculosis and Treatment.

PMID- 18736338
TI  - Why Are Better Results Not Being Obtained in the Prevention and Treatment of
      Tuberculosis?

PMID- 18736339
TI  - Some Laboratory Aids in the Diagnosis of Tuberculosis.

PMID- 18736340
TI  - The Prognosis of Pulmonary Tuberculosis.

PMID- 18736342
TI  - The Bureau of Tuberculosis, Its Work and Plans.

PMID- 18736341
TI  - The Treatment of Pulmonary Hemorrhage.

PMID- 18736343
TI  - Arequipa Sanatorium, A Sociological and Economic Experiment in the Care of
      Tuberculous Wage Earning Girls.

PMID- 18736344
TI  - Social Insurance in Its Relation to Tuberculosis.

PMID- 18736345
TI  - INDUCED PNEUMOTHORAX.

PMID- 18736346
TI  - DIAGNOSIS, SIGNIFICANCE AND TREATMENT OF BRONCHIAL GLANDS IN INFANCY AND
      CHILDHOOD.

PMID- 18736347
TI  - INDICATION FOR THE LABYRINTH OPERATION, WITH REPORT OF EIGHT CASES THAT WERE NOT
      OPERATED UPON.

PMID- 18736348
TI  - THE INTRASPINOUS TREATMENT OF TABES. PRELIMINARY REPORT.

PMID- 18736349
TI  - UTERINE REPLACEMENT; WITH PARTICULAR ATTENTION TO THE BUTEAU SUSPENSION.

PMID- 18736350
TI  - BUTTERMILK AND GREENS TREATMENT OF THREE CASES OF GRAVE SECONDARY ANEMIA.

PMID- 18736352
TI  - A CRUSADE AGAINST MEDICAL LICENSURE.

PMID- 18736351
TI  - THE DANGERS OF VAGINAL EXAMINATIONS DURING LABOR.

PMID- 18736354
TI  - SOCIETY REPORT.

PMID- 18736353
TI  - THE HARMLESS LITTLE FLY.

PMID- 18736355
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736356
TI  - PROSECUTIONS UNDER THE LAW.

PMID- 18736357
TI  - NEW AND NONOFFICIAL REMEDIES.

PMID- 18736359
TI  - FULL TIME TEACHING SECURED.

PMID- 18736358
TI  - DR. VAUGHAN'S REPORT ON STANFORD.

PMID- 18736361
TI  - THE OSTEOPATHIC SITUATION.

PMID- 18736360
TI  - OUR DELEGATES AT THE ATLANTIC CITY MEETING.

PMID- 18736362
TI  - MILITARY SURGERY.

PMID- 18736363
TI  - THE STATE UNIVERSITY ESTABLISHES A GRADUATE SCHOOL AT LOS ANGELES.

PMID- 18736364
TI  - The Intimate Relation of Orthopedic Surgery to Neurology.

PMID- 18736365
TI  - WAR AND ITS ROMANCE.

PMID- 18736366
TI  - THE EXPOSITION AND THE WAR.

PMID- 18736368
TI  - Surgery of Peptic Ulcer.

PMID- 18736367
TI  - The Treatment of Gastric and Duodenal Ulcer.

PMID- 18736369
TI  - The Dose of Salvarsan.

PMID- 18736370
TI  - The Early Diagnosis of Cancer of the Rectum.

PMID- 18736371
TI  - Psychotherapy in Urology.

PMID- 18736372
TI  - Photography in Relation to the Medical Sciences.

PMID- 18736373
TI  - REPORT OF A CASE OF OIDIOMYCOSIS.

PMID- 18736374
TI  - PERFORATED DUODENAL-ULCER REPORT OF AN UNUSUAL CASE.

PMID- 18736375
TI  - THE VALUE OF HIGH FREQUENCY CURRENT IN TREATING CALCULI IN A DIVERTICULUM.

PMID- 18736376
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736377
TI  - CASE OF ACUTE APPENDICITIS (WITH EARLY OPERATION).

PMID- 18736378
TI  - TO OUR ADVANTAGE.

PMID- 18736380
TI  - GRUESOMELY HUMOROUS!

PMID- 18736379
TI  - REAL HELP.

PMID- 18736381
TI  - RISING PRICES.

PMID- 18736382
TI  - COUNCIL MEETING.

PMID- 18736384
TI  - OUR REAL WORK.

PMID- 18736383
TI  - A GOOD NUMBER.

PMID- 18736385
TI  - BUBONIC PLAGUE IN NEW ORLEANS.

PMID- 18736386
TI  - NEW DODGE IN FAKERY.

PMID- 18736387
TI  - PUBLIC HEALTH SERVICE EXAMINATIONS.

PMID- 18736388
TI  - AMERICAN MEDICAL MEETING.

PMID- 18736389
TI  - Progress of Pediatrics: I. Problems of Breast Nursing.

PMID- 18736391
TI  - Radiologic Diagnosis of Gastro-Duodenal Ulcers.

PMID- 18736390
TI  - Duodenal Feeding-A Practical Demonstration.

PMID- 18736392
TI  - Medical Management of Duodenal Ulcer.

PMID- 18736393
TI  - Gastro-Duodenal Ulcer; Symptomatology and Diagnosis.

PMID- 18736394
TI  - Three Cases With Relaxed Pelvic Supports.

PMID- 18736395
TI  - Novocain Poisoning.

PMID- 18736396
TI  - The Function of the General Practitioner in Relation to the Study and Prevention
      of Nervous and Mental Diseases.

PMID- 18736397
TI  - THE INDUCTION OF ANESTHESIA AND ETHYL CHLORIDE.

PMID- 18736398
TI  - HAIR-BALL TUMOR OF THE STOMACH.

PMID- 18736399
TI  - INTRANASAL OPERATION FOR DACRYOSTENOSIS, WITH CASE HISTORIES.

PMID- 18736400
TI  - SHOCKLESS SURGERY.

PMID- 18736401
TI  - THE NURSING SITUATION SINCE THE PASSAGE OF THE LAW.

PMID- 18736402
TI  - SOCIETY REPORT.

PMID- 18736404
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736403
TI  - ILLEGALS PROSECUTED.

PMID- 18736405
TI  - WHAT CONSTITUTES FIRST AID?

PMID- 18736407
TI  - POST GRADUATE COURSE FOR NURSES.

PMID- 18736406
TI  - EIGHT-HOUR LAW FOR NURSES.

PMID- 18736409
TI  - PUBLIC HEALTH SERVICE.

PMID- 18736408
TI  - TRAVEL STUDY CLUB.

PMID- 18736411
TI  - A. M. A. MEETING, JUNE 1915.

PMID- 18736410
TI  - CRIME NO. 46.

PMID- 18736412
TI  - REAL THANKS-GIVING.

PMID- 18736413
TI  - EXPERT TESTIMONY.

PMID- 18736414
TI  - NO STATE SOCIETY MEETING IN 1915.

PMID- 18736415
TI  - PRICES AND SUPPLIES.

PMID- 18736416
TI  - MORE REAL HELP.

PMID- 18736417
TI  - COUNCIL MEETING.

PMID- 18736418
TI  - Early Symtomatology of Subacute Bacterial Endocarditis.

PMID- 18736419
TI  - APPARENTLY UNJUST.

PMID- 18736420
TI  - Medical Hospital Bookkeeping.

PMID- 18736421
TI  - Leukocytic Extract in the Treatment of Pneumoccus Injection in Rabbits.

PMID- 18736423
TI  - Status Lymphaticus.

PMID- 18736422
TI  - Case of Paroxysmal Hemoglobinuria Treated with Salvarsan.

PMID- 18736425
TI  - Relation of Local Infections to Joint Affections.

PMID- 18736424
TI  - Consideration of Nasal Conditions Causing Asthma.

PMID- 18736426
TI  - Curative Treatment of Pneumonia, with a Report on the Use of Leukocytic Extract.

PMID- 18736428
TI  - THE PREVENTION OF TUBERCULOSIS IN CHILDREN.

PMID- 18736427
TI  - COMPLICATIONS IN CATARACT EXTRACTION.

PMID- 18736429
TI  - DECOMPRESSION IN ACQUIRED INTERNAL HYDROCEPHALUS: Report of Case.

PMID- 18736431
TI  - A CASE OF ACHONDROPLASIA (FETAL RICKETS).

PMID- 18736430
TI  - WET NURSE DIRECTORY: Established at the University Hospital.

PMID- 18736433
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736432
TI  - SOCIETY REPORT.

PMID- 18736435
TI  - WESTERN ORTHOPEDIC CLUB.

PMID- 18736434
TI  - A SUGGESTION REGARDING CO-OPERATION.

PMID- 18736436
TI  - RICE WANTED.

PMID- 18736438
TI  - CHRISTMAS GREETINGS.

PMID- 18736437
TI  - STAINING TUBERCLE BACILLUS.

PMID- 18736439
TI  - TO COUNTY SECRETARIES.

PMID- 18736440
TI  - A. M. A. MEETING IN JUNE; ARRANGEMENTS COMMITTEE.

PMID- 18736442
TI  - THERE IS A PUBLICATION COMMITTEE.

PMID- 18736441
TI  - NEVADA STATE ASSOCIATION.

PMID- 18736443
TI  - A WORD ON PAPERS.

PMID- 18736444
TI  - THE RIGHT SPIRIT AND THE RIGHT KIND OF HELP.

PMID- 18736446
TI  - UNREST IN NEW YORK STATE.

PMID- 18736445
TI  - GUARD YOUR MEMBERSHIP!

PMID- 18736447
TI  - Primary Sarcoma of the Stomach; Report of a Case Treated by Partial Gastrectomy.

PMID- 18736449
TI  - Infantile and Juvenile Tabes.

PMID- 18736448
TI  - Bone Splinting in Vertebral Tuberculosis: A Year's Work at the Children's
      Hospital, San Francisco.

PMID- 18736450
TI  - Feeding in the First Month of Life.

PMID- 18736451
TI  - Centralization of Public Health Administration.

PMID- 18736452
TI  - Points of Interest in the Technic of Gastro-Enterostomy.

PMID- 18736454
TI  - A Report of Two Unusual Cases of Hernia with Abstract of the Literature.

PMID- 18736453
TI  - Does a Relationship Exist Between Tuberculosis of the Epididymis and Tuberculosis
      of the Kidney?

PMID- 18736455
TI  - The Mendelian Law and Its Relation to Inherited Conditions of the Eye.

PMID- 18736456
TI  - CONSERVATIVE AMPUTATIONS OF THE LOWER EXTREMITIES.

PMID- 18736457
TI  - A CASE OF ABDOMINAL PREGNANCY.

PMID- 18736459
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736458
TI  - SOCIETY REPORT.

PMID- 18736460
TI  - THE EXHIBITS WILL BE ON HAND.

PMID- 18736462
TI  - SOME OF OUR DISEASES.

PMID- 18736461
TI  - CALIFORNIA STATE BOARD OF HEALTH CIRCULAR ON PELLAGRA.

PMID- 18736464
TI  - NOTHING NEW UNDER THE SUN.

PMID- 18736463
TI  - ARMY MEDICAL CORPS EXAMINATIONS.

PMID- 18736465
TI  - THE NEW YEAR-AND GREETINGS!

PMID- 18736466
TI  - SPECIALS TO THE A. M. A., SAN FRANCISCO, 1915.

PMID- 18736467
TI  - WHAT IS HONESTY?

PMID- 18736468
TI  - Official Medical Experts.

PMID- 18736469
TI  - Official Medical Experts.

PMID- 18736471
TI  - The Cure of Syphilis.

PMID- 18736470
TI  - The Medical Expert in American Jurisprudence.

PMID- 18736473
TI  - "PHYSICIANS' PROTECTIVE ASSOCIATION" NOT ENDORSED BY STATE SOCIETY.

PMID- 18736472
TI  - COUNTY UNITS, BE CAREFUL!

PMID- 18736475
TI  - SPLENDID WORK.

PMID- 18736474
TI  - MAIL-ORDER FRAUDS AND OTHER PAMPHLETS.

PMID- 18736476
TI  - WORTH REPETITION.

PMID- 18736477
TI  - Progress in Obstetrics.

PMID- 18736478
TI  - The Relation of the Periosteum to Bone Vitality.

PMID- 18736479
TI  - The Utility of Catarrhal Vaccines.

PMID- 18736480
TI  - Some Causes of Frequent and Painful Micturition in Women.

PMID- 18736482
TI  - IMPORTANT NOTICE!: New Medical Defense Rules.

PMID- 18736481
TI  - ONE-SIDED "RECIPROCITY.".

PMID- 18736483
TI  - FRACTURES; SUITS; X-RAY PLATES.

PMID- 18736484
TI  - HOW IT PAYS TO ADVERTISE.

PMID- 18736485
TI  - Nutritional Disturbances of Infancy.

PMID- 18736487
TI  - SOCIETY REPORT.

PMID- 18736486
TI  - A CASE OF COMPLETE DUPLICATION OF THE RENAL PELVIS AND URETER.

PMID- 18736488
TI  - REMEDIES FOR INDIGESTION MUST BE PROPERLY PREPARED AND SOLD WHILE FRESH.

PMID- 18736489
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736490
TI  - MEDICAL ERRORS AND EDUCATION.

PMID- 18736491
TI  - WAR TAX: Office of Collector of Internal Revenue, First District of California.

PMID- 18736492
TI  - LIP READING FOR THE DEAF.

PMID- 18736493
TI  - TUBERCULOSIS AND RED CROSS STAMPS.

PMID- 18736494
TI  - Expert Witness from the Standpoint of the Attorney.

PMID- 18736495
TI  - DUES! DUES! DUES!

PMID- 18736496
TI  - WARNING!: New Law; Heavy Penalties!

PMID- 18736498
TI  - LEGISLATION.

PMID- 18736497
TI  - "RECIPROCITY" AGAIN.

PMID- 18736500
TI  - MR. KAUFMAN.

PMID- 18736499
TI  - MEDICAL DEFENSE RESULTS.

PMID- 18736501
TI  - BOUND TO PUBLISH IT.

PMID- 18736502
TI  - REMARKS TO LEGISLATORS.

PMID- 18736503
TI  - DRUGGIST CO-OPERATION.

PMID- 18736504
TI  - THE RIGHT KIND OF TALK.

PMID- 18736505
TI  - SMOOTH SWINDLER; LOOK OUT FOR HIM.

PMID- 18736506
TI  - MEMBERSHIP VS. LICENSE TO PRACTICE.

PMID- 18736507
TI  - Operations in the Eye Clinics of Stanford University.

PMID- 18736508
TI  - Skin Test in Typhoid.

PMID- 18736509
TI  - Pregnancy Toxaemias-Their Etiology and Treatment.

PMID- 18736510
TI  - Inflamed Eye-Some Comments on Its Diagnosis.

PMID- 18736511
TI  - Operative Procedures of Ocular Muscles in Heterophories.

PMID- 18736512
TI  - Conservative Management of the Handicapped Gynecological Patient.

PMID- 18736513
TI  - Report on Ehrlich's Aldehyde Test for Urobilinogen.

PMID- 18736514
TI  - Concerning the Etiology and Treatment of Superflous Hair.

PMID- 18736515
TI  - Reasonable Treatment for Typhoid.

PMID- 18736517
TI  - Tubercular Peritonitis.

PMID- 18736516
TI  - Ureteral Defect Repaired With Loop of Intestines-Report of Case.

PMID- 18736518
TI  - COMPOUND FRACTURE OF BOTH FEMURS WITH EXTENSIVE LACERATION OF SOFT PARTS.

PMID- 18736519
TI  - THE ADVENT OF CHINESE DOCTORS INTO CALIFORNIA.

PMID- 18736520
TI  - A CASE OF ACUTE PANCREATITIS WITH AN ACCOMPANYING PSEUDO-CYST.

PMID- 18736522
TI  - SOCIETY REPORT.

PMID- 18736521
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736524
TI  - POISONOUS FLY DESTROYERS.

PMID- 18736523
TI  - STATE HEALTH CREED.

PMID- 18736525
TI  - SERUM FOR INFLUENZAL MENINGITIS.

PMID- 18736526
TI  - THE MEDICAL ASSOCIATION OF THE ISTHMIAN CANAL ZONE.

PMID- 18736527
TI  - A Case of Anthrax.

PMID- 18736528
TI  - The Perversion of Forces in and About the Oral Cavity.

PMID- 18736529
TI  - Endocarditis with Streptococemia.

PMID- 18736530
TI  - After Medicine, What?

PMID- 18736531
TI  - Spinal Anesthesia.

PMID- 18736532
TI  - Combined Treatment of Syphilis with Mercury and Salvarsan.

PMID- 18736533
TI  - The Clinical Value of Percussion of the Skull.

PMID- 18736534
TI  - GUN-SHOT WOUND OF THE EAR WITH REPORT OF TWO CASES.

PMID- 18736535
TI  - REPORT OF AN UNUSUAL CASE OF LABYRINTHINE DEAFNESS.

PMID- 18736536
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736537
TI  - SOCIETY REPORTS.

PMID- 18736538
TI  - A MISUNDERSTANDING.

PMID- 18736539
TI  - OPINIONS REGARDING MEDICAL DEFENSE RULES.

PMID- 18736541
TI  - THE EXPOSITION AND THE A. M. A.

PMID- 18736540
TI  - THAT FEDERAL DRUG LAW.

PMID- 18736542
TI  - A SUGGESTION FOR COUNTY SOCIETY WORK.

PMID- 18736544
TI  - PLENTY OF GOOD WATER.

PMID- 18736543
TI  - HEARING ON MEDICAL BILLS.

PMID- 18736545
TI  - THE VIAVI FRAUD ONCE MORE.

PMID- 18736546
TI  - EXPERIENCE IN ADVERTISING; A FACT.

PMID- 18736547
TI  - INCOME TAX.

PMID- 18736548
TI  - ASSEMBLY BILL NO. 923.

PMID- 18736549
TI  - Dystocia Due to a Funnel Pelvis.

PMID- 18736550
TI  - Increased Blood Pressure.

PMID- 18736551
TI  - DIPHTHERIA EPIDEMIC; WARNING.

PMID- 18736552
TI  - JUNE 21; A. M. A.; EXPOSITION.

PMID- 18736553
TI  - HOTEL RATES.

PMID- 18736554
TI  - REGISTER AND DIRECTORY.

PMID- 18736555
TI  - THE CANCER PROBLEM.

PMID- 18736557
TI  - MEDICAL DEFENSE DISCUSSION.

PMID- 18736556
TI  - OSTEOPATHIC "DOCTORS.".

PMID- 18736559
TI  - THE IMPUDENCE OF T. FLOYD BROWN, M. D.

PMID- 18736558
TI  - TO LICENSE CALIFORNIA GRADUATES WITHOUT EXAMINATION.

PMID- 18736560
TI  - OUR LAW DEPARTMENT.

PMID- 18736561
TI  - VENARSEN.

PMID- 18736563
TI  - Haematogenous Kidney Infections.

PMID- 18736562
TI  - The Reduction of Diphtheria Morbidity.

PMID- 18736564
TI  - The Operation on Suprapubic Prostatectomy and Some of Its Results.

PMID- 18736565
TI  - The Carrier Problem in Diphtheria.

PMID- 18736566
TI  - Retrodisplacement of the Pregnant Uterus.

PMID- 18736567
TI  - Case of Pellagra.

PMID- 18736568
TI  - California Pediatric Society-Northern Branch.

PMID- 18736569
TI  - SOCIETY REPORTS.

PMID- 18736570
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736571
TI  - THE HARRISON LAW A NATIONAL OBLIGATION.

PMID- 18736572
TI  - THE PHYSICIAN AND THE HARRISON NARCOTIC LAW.

PMID- 18736573
TI  - FEDERAL OPIUM-COCA LAW.

PMID- 18736575
TI  - NOVOCAIN.

PMID- 18736574
TI  - DR. CARREL'S WORK IN FRANCE.

PMID- 18736576
TI  - DEFENSE BY INSURANCE COMPANIES.

PMID- 18736577
TI  - EXPOSITION-YEAR VACATION AND THE A. M. A.

PMID- 18736579
TI  - INVESTIGATE ALL APPLICANTS.

PMID- 18736578
TI  - LEGAL ABSURDITY.

PMID- 18736580
TI  - THE MEDICAL TRUST!

PMID- 18736581
TI  - IMPORTANCE OF CASE RECORDS.

PMID- 18736582
TI  - THE PASSING OF THE DETAIL MAN.

PMID- 18736583
TI  - MEDICAL COMMENT ON WAR VICTIMS.

PMID- 18736584
TI  - SUMMER GRADUATE MEDICAL COURSE.

PMID- 18736585
TI  - THE HARRISON LAW; CONSCIENCE OR CUPIDITY?

PMID- 18736586
TI  - NEW AND NON-OFFICIAL REMEDIES, 1915.

PMID- 18736587
TI  - Luetin Reaction in Syphilis.

PMID- 18736589
TI  - General Paresis and Its Relation to Syphilis.

PMID- 18736588
TI  - Diagnosis of Gastrointestinal Disease: Illustrated by Forty Operative Cases-April
      October, 1914.

PMID- 18736590
TI  - LABORATORY REPORT, NAPA STATE HOSPITAL.

PMID- 18736591
TI  - The Harrison Anti-Narcotic Act.

PMID- 18736592
TI  - Functional Defects of the Thyroid in Relation to Neurotic Conditions.

PMID- 18736593
TI  - Successful Methods of Attack on Malaria in California.

PMID- 18736594
TI  - Drug Anaphylaxis: an Illustrative Case.

PMID- 18736595
TI  - Report of Three Years' Rectal Work at the County Hospital.

PMID- 18736597
TI  - A Water-Borne Typhoid Fever Epidemic.

PMID- 18736596
TI  - A Consideration of the Relative Merits of the Albee Operation and the Hibbs
      Operation.

PMID- 18736598
TI  - Request For Information Regarding Typhoid Vaccine.

PMID- 18736600
TI  - CASE REPORT: Fracture of the Left Clavicle by Muscular Action (Without Blow or
      Fall).

PMID- 18736599
TI  - School Hygiene Congress.

PMID- 18736601
TI  - AN ACCIDENT WITH NEO-SALVARSAN.

PMID- 18736602
TI  - SOCIETY REPORTS.

PMID- 18736603
TI  - EFFECTS OF THE HARRISON LAW.

PMID- 18736604
TI  - STATE COMPENSATION INSURANCE FUND: Care of Industrial Accidents.

PMID- 18736605
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736606
TI  - TUBERCULOSIS EXHIBIT AT EXPOSITION.

PMID- 18736607
TI  - $1,000 PRIZE.

PMID- 18736609
TI  - WARREN TRIENNIAL PRIZE: Massachusetts General Hospital.

PMID- 18736608
TI  - SCHICK REACTION.

PMID- 18736611
TI  - MEDICAL PIRATES CONVICTED.

PMID- 18736610
TI  - NAVY MEDICAL CORPS.

PMID- 18736613
TI  - REPORT APPLICANTS.

PMID- 18736612
TI  - AMERICAN MEDICAL ASSOCIATION MEETING.

PMID- 18736615
TI  - PRESENT DAY KNOWLEDGE.

PMID- 18736614
TI  - AMENDMENTS TO THE MEDICAL LAW.

PMID- 18736616
TI  - PASSED AND FAILED; CALIFORNIA SCHOOLS.

PMID- 18736617
TI  - POLITICS AND HEALTH-OFFICER.

PMID- 18736618
TI  - APPENDICITIS AND THE LAW.

PMID- 18736619
TI  - TWILIGHT SLEEP.

PMID- 18736620
TI  - MEDICAL MILK COMMISSIONS.

PMID- 18736621
TI  - SENATORIAL SENSE.

PMID- 18736622
TI  - THE DETAIL MAN-AN ECONOMIC WASTE.

PMID- 18736623
TI  - INDUSTRIAL SICKNESS INSURANCE.

PMID- 18736624
TI  - HARRISON NARCOTIC LAW.

PMID- 18736625
TI  - Morphine-Scopolamine Anesthesia in Obstetrics.

PMID- 18736626
TI  - A POSSIBLE EXPLANATION OF THE CONFLICTING REPORTS ON TWILIGHT SLEEP.

PMID- 18736627
TI  - Observations on the Dammerschlaf or Twilight Sleep.

PMID- 18736628
TI  - THE SILVER IODIDE EMULSION IN PYELOGRAPHY.

PMID- 18736629
TI  - Case of Sympathetic Ophthalmia.

PMID- 18736630
TI  - Some Experimental Data on the Morestin Treatment of Peritonitis.

PMID- 18736631
TI  - Streptococci Infections.

PMID- 18736633
TI  - More or Less Medical Bills.

PMID- 18736632
TI  - United States Public Health Service.

PMID- 18736634
TI  - County Societies.

PMID- 18736635
TI  - LELAND STANFORD JUNIOR UNIVERSITY SCHOOL OF MEDICINE.

PMID- 18736637
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736638
TI  - THE MEDICAL PRACTICE ACT.

PMID- 18736639
TI  - MEDICAL CORPS OF THE UNITED STATES NAVY.

PMID- 18736641
TI  - A. M. A.

PMID- 18736640
TI  - EXAMINATION OF CANDIDATES FOR ASSISTANT SURGEON-PUBLIC HEALTH SERVICE.

PMID- 18736642
TI  - PHYSICIAN'S RIGHTS.

PMID- 18736643
TI  - PATIENT'S RIGHTS.

PMID- 18736644
TI  - TERMINATION OF SERVICES.

PMID- 18736645
TI  - ILLEGAL PRACTITIONERS.

PMID- 18736646
TI  - PHYSICIANS OF SAN FRANCISCO, PLEASE REGISTER!

PMID- 18736648
TI  - FEDERAL CONVICTIONS.

PMID- 18736647
TI  - APPLICANTS.

PMID- 18736649
TI  - JUNE MEETINGS.

PMID- 18736650
TI  - MAYO CLINIC AND THE UNIVERSITY OF MINNESOTA.

PMID- 18736651
TI  - A SPONGE IN THE BELLY.

PMID- 18736652
TI  - DOCTORS' OFFICE ROBBER.

PMID- 18736653
TI  - EXAMINE THE PLACENTA.

PMID- 18736654
TI  - Treatment of Infection.

PMID- 18736655
TI  - The Use of the Lane Plates in Fractures.

PMID- 18736657
TI  - Progress of Ophthalmology in the Year 1914.

PMID- 18736656
TI  - Gas Bacillus Infection.

PMID- 18736658
TI  - Suggestions of Billary Tract Surgery for the General Practitioner.

PMID- 18736659
TI  - Some Recent Studies in Gastric Secretion.

PMID- 18736660
TI  - Routine Examination of the Cerebrospinal Fluid in Suspected Syphilis of the
      Nervous System.

PMID- 18736661
TI  - Autonomic Reflexes From the Digestive Tract.

PMID- 18736662
TI  - The Ring to Ring Incision for Herniorrhaphy.

PMID- 18736663
TI  - PERTUSSIS: A RESUME OF OUR PRESENT KNOWLEDGE.

PMID- 18736664
TI  - THE UROBILIN TEST IN MALARIA.

PMID- 18736665
TI  - ASTRAGALECTOMY FOR TUBERCULOSIS OF THE TARSUS: From the Orthopedic Clinic of
      Stanford University.

PMID- 18736666
TI  - SOCIETY REPORTS.

PMID- 18736667
TI  - ADDRESS TO BE DELIVERED OVER THE BODY OF A YOUNG MAN DEAD OF TYPHOID FEVER.

PMID- 18736668
TI  - PANAMA CANAL.

PMID- 18736670
TI  - THE BAKING-POWDER PROBLEM.

PMID- 18736669
TI  - MEDICAL BILLS.

PMID- 18736671
TI  - THE BACTERIOLOGY OF APPENDICITIS.

PMID- 18736672
TI  - CALIFORNIA AND THE A. M. A.

PMID- 18736674
TI  - PUBLIC HEALTH DAY.

PMID- 18736673
TI  - REMEMBER YOUR FRIENDS.

PMID- 18736676
TI  - NARCOTIC DRUGS IN HOSPITAL USE.

PMID- 18736675
TI  - PROGRESS OR RETROGRESSION?

PMID- 18736678
TI  - HEALTHY GROWTH IN CALIFORNIA.

PMID- 18736677
TI  - DO NOT PRINT YOUR LICENSE NUMBER.

PMID- 18736680
TI  - GOOD LEGISLATORS-AND OTHERS.

PMID- 18736679
TI  - DR. RODMAN AND "THE COLLEGE".

PMID- 18736681
TI  - MERELY MONEY!

PMID- 18736683
TI  - VANDERBURGH AND THE "HOG-TIGHT FENCE".

PMID- 18736682
TI  - THE MEDICAL PERIOD.

PMID- 18736685
TI  - Notes on Angina Pectoris.

PMID- 18736684
TI  - Some Typical Experiences With Syphilitic Patients.

PMID- 18736686
TI  - Dermatitis Caused by Primula Poisoning.

PMID- 18736687
TI  - The Early Diagnosis of Pulmonary Tuberculosis.

PMID- 18736688
TI  - The Occurrence of Heart Block in Acute Diseases.

PMID- 18736689
TI  - Pitfalls in the Diagnosis of Renal Lithiasis.

PMID- 18736690
TI  - Pediatric Situation in Europe and the Effect of the War on the Same.

PMID- 18736691
TI  - Tuberculosis of the Female Genitals.

PMID- 18736692
TI  - PERSONAL EXPERIENCE WITH CHOLECYSTECTOMY.

PMID- 18736693
TI  - FISCHER'S THEORY OF EDEMA.

PMID- 18736695
TI  - SOCIETY REPORTS.

PMID- 18736694
TI  - PAN-AMERICAN MEDICAL CONGRESS.

PMID- 18736696
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736698
TI  - CITY TUBERCULOSIS CLINICS.

PMID- 18736697
TI  - CALIFORNIA SOCIAL HYGIENE SOCIETY.

PMID- 18736700
TI  - THAT "HOG-TIGHT FENCE" AGAIN.

PMID- 18736699
TI  - LANE MEDICAL LECTURES.

PMID- 18736702
TI  - ONE DANGER OF IT.

PMID- 18736701
TI  - OSTEOPATHIC M.D.'S, AND HOW.

PMID- 18736703
TI  - SUGGESTIONS TO MEDICAL AUTHORS.

PMID- 18736704
TI  - THE WHY OF IT.

PMID- 18736705
TI  - RAIDS ON QUACKS.

PMID- 18736706
TI  - INDUSTRIAL INSURANCE.

PMID- 18736707
TI  - THE HAND OF THE DEVIL, ONCE MORE.

PMID- 18736708
TI  - THE STATE MEDICAL SOCIETY AND PLAGUE.

PMID- 18736709
TI  - Typhoid Fever: A Resume of Present-Day Knowledge.

PMID- 18736711
TI  - President's Address-16th Annual Meeting of the American Therapeutic Society,
      June, 1915, San Francisco: Some Observations on the Present Status of American
      Medical Journalism.

PMID- 18736710
TI  - Statistics of My New Advancement Operation, with Report of Cases.

PMID- 18736712
TI  - The Diagnosis of Congenital Syphilis.

PMID- 18736713
TI  - Gastro-Intestinal Symptoms in Diseases of the Circulatory System.

PMID- 18736714
TI  - Benzene Treatment of Leukemia.

PMID- 18736716
TI  - Roentgen Ray Treatment of Leukemia.

PMID- 18736715
TI  - The Blood in Leukemia.

PMID- 18736717
TI  - Shall the Medical Society of the State of California Have an Examining Board?

PMID- 18736719
TI  - BANTI'S DISEASE.

PMID- 18736718
TI  - THE ROUTINE EXAMINATION IN A GENERAL HOSPITAL FOR DIPHTHERIA CARRIERS AND A NOTE
      ON THE SCHICK REACTION.

PMID- 18736720
TI  - LANE MEDICAL LECTURES, 1915.

PMID- 18736721
TI  - SOCIETY REPORTS.

PMID- 18736722
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736724
TI  - PANAMA-PACIFIC DENTAL CONGRESS.

PMID- 18736723
TI  - SAN FRANCISCO SESSION.

PMID- 18736725
TI  - EXAMINATION OF SCHOOL CHILDREN.

PMID- 18736726
TI  - VACATIONS BRING TYPHOID: State Board of Health Issues Warning to Campers.

PMID- 18736728
TI  - PUBLIC HEALTH BILLS, CONTINUED.

PMID- 18736727
TI  - "ARTICLES OF FAITH" CONCERNING CANCER: A Platform Upon Which to Unite in the
      Campaign of Education.

PMID- 18736730
TI  - A. L. LENGFELD, M.D.

PMID- 18736729
TI  - REPORT OF THE TUBERCULOSIS SITUATION IN SAN FRANCISCO.

PMID- 18736731
TI  - RECORDS-RECORDS-RECORDS!!

PMID- 18736733
TI  - State Meeting, Fresno.

PMID- 18736732
TI  - THE SAFETY OF PATIENTS.

PMID- 18736734
TI  - DOCTORS AND CHARITY.

PMID- 18736735
TI  - MEDICAL PRACTICE ACTS.

PMID- 18736736
TI  - TUBERCULOSIS-WARNING.

PMID- 18736738
TI  - Nerve Injuries: Their Influence on the Period of Disability.

PMID- 18736737
TI  - PROGRESS OR RETROGRESSION?

PMID- 18736739
TI  - The Relation of the So-Called Strained Back to Disability Following Industrial
      Accidents.

PMID- 18736740
TI  - Traumatic Neuroses in Relation to Industrial Accidents. Prognosis and Treatment.

PMID- 18736741
TI  - Some Remarks on Industrial Insurance Work.

PMID- 18736742
TI  - Internal Medicine in Relation to Industrial Accidents.

PMID- 18736743
TI  - Fracture Records; A National Effort Toward Standardization.

PMID- 18736744
TI  - The Use of Carbon Dioxid in Dermatology.

PMID- 18736745
TI  - THE RELATION OF CERTAIN URINARY FINDINGS TO PROGNOSIS ON PULMONARY TUBERCULOSIS.

PMID- 18736746
TI  - CONTRIBUTION TO INFECTION; ITS PREVENTION AND TREATMENT. RESULTS IN 500 TRAUMATIC
      CASES.

PMID- 18736747
TI  - THE SCOPE AND LIMITATIONS OF A PSYCHIATRIC CLINIC IN SAN FRANCISCO.

PMID- 18736748
TI  - ADDRESS OF WELCOME DELIVERED BEFORE THE PACIFIC COAST OTO-OPHTHALMOLOGICAL
      SOCIETY AT SAN FRANCISCO, CALIFORNIA.

PMID- 18736749
TI  - PULSATING EXOPHTHALMOS TREATED BY SLOW OCCLUSION OF THE COMMON CAROTID ARTERY
      WITH THE NEFF CLAMP.

PMID- 18736751
TI  - IN ERRATA.

PMID- 18736750
TI  - SOCIETY REPORTS.

PMID- 18736752
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736753
TI  - TUBERCULOSIS FIGHT IN SAN FRANCISCO.

PMID- 18736755
TI  - THE SO-CALLED NEW ANTISEPTIC.

PMID- 18736754
TI  - FLIES AND DIARRHEAL DISEASE: Publication No. 91, New York Association for
      Improving the Condition of the Poor.

PMID- 18736756
TI  - ITEMS OF INTEREST.

PMID- 18736757
TI  - RESTRICTED PRACTICE FOR DRUGLESS PRACTITIONERS.

PMID- 18736758
TI  - CALIFORNIA.

PMID- 18736759
TI  - CANNING COMPOUNDS DANGEROUS TO HEALTH.

PMID- 18736760
TI  - ON CRITICISM.

PMID- 18736762
TI  - THIS REALLY HAPPENED.

PMID- 18736761
TI  - FRAUDS IN MEDICINE; LEARN ABOUT THEM.

PMID- 18736763
TI  - ROCKEFELLER FOUNDATION AND HOOKWORM.

PMID- 18736764
TI  - ON ACCOUNTS.

PMID- 18736766
TI  - IMPROVING CONDITIONS.

PMID- 18736765
TI  - TEST YOUR WASSERMANN!

PMID- 18736768
TI  - RIGHTS AND DUTIES UNDER HEALTH LAWS.

PMID- 18736767
TI  - SANITATION POSSIBILITIES.

PMID- 18736770
TI  - LESSONS FOR LAYMEN.

PMID- 18736769
TI  - ANOTHER "CURE FOR CANCER.".

PMID- 18736772
TI  - PLAGUE HISTORY.

PMID- 18736771
TI  - EXTRACT OF LIVER, A FUTURIST REMEDY.

PMID- 18736773
TI  - NO DOCTORS NEEDED-USE "AKOZ"!

PMID- 18736774
TI  - Scarlatina: A Resume of Present-Day Knowledge.

PMID- 18736775
TI  - The Modern Diagnosis of Hematuria.

PMID- 18736776
TI  - Clinical Records.

PMID- 18736777
TI  - Conditions in the Lower Back Involving the Sacro-Lumbar and Sacro-Iliac
      Articulations.

PMID- 18736778
TI  - Diagnosis of Ureteral Calculi-Technic for use of the Waxtipped Catheter in the
      male.

PMID- 18736779
TI  - Preliminary Report on the Finding of Arsenic in the Cerebrospinal Fluid following
      Intravenous Administration of Neosalvarsan.

PMID- 18736780
TI  - Panama-Pacific Dental Congress.

PMID- 18736781
TI  - EXTRACTS FROM IMPROMPTU TALK AND RADIOGRAPH EXHIBIT. PANAMA-PACIFIC DENTAL
      CONGRESS, AUGUST-SEPTEMBER, 1915.

PMID- 18736782
TI  - BLOOD TRANSFUSION SIMPLIFIED.

PMID- 18736783
TI  - A PAPER-BAG HOLDER FOR THE RECEPTION OF SOILED SURGICAL DRESSINGS.

PMID- 18736784
TI  - SOCIETY REPORTS.

PMID- 18736785
TI  - THE LODGE DOCTOR.

PMID- 18736786
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736787
TI  - THE FORTUNE OF A NOSTRUM MAN.

PMID- 18736788
TI  - NEW AND NONOFFICIAL REMEDIES.

PMID- 18736789
TI  - THE SO-CALLED NEW ANTISEPTIC.

PMID- 18736790
TI  - CONTROLLING CANCER IN ENGLAND.

PMID- 18736791
TI  - AN ENGLISH SUCCESSOR TO A GERMAN NOSTRUM.

PMID- 18736792
TI  - MEASLES AND WHOOPING-COUGH GREAT FOES OF CHILDREN.

PMID- 18736794
TI  - EDUCATION AT THE EXPOSITION.

PMID- 18736793
TI  - RURAL CREDITS.

PMID- 18736796
TI  - RACE BETTERMENT.

PMID- 18736795
TI  - NAVY SURGEONS.

PMID- 18736798
TI  - BUSINESS!!

PMID- 18736799
TI  - NEVADA STATE MEETING.

PMID- 18736797
TI  - SOCIAL SERVICE SCHOOL.

PMID- 18736801
TI  - DANGER AVERTED.

PMID- 18736800
TI  - DECEMBER-THE END OF ANOTHER YEAR.

PMID- 18736803
TI  - SOCIAL INSURANCE.

PMID- 18736802
TI  - TAXING PHYSICIANS.

PMID- 18736804
TI  - PHOTOGRAPHS, PLEASE!

PMID- 18736805
TI  - RAY LYMAN WILBUR, M. D., COUNTRY DOCTOR, PRESIDENT OF STANFORD.

PMID- 18736806
TI  - HAY-FEVER IN CALIFORNIA?

PMID- 18736807
TI  - PUBLIC HEALTH; MEDICAL JURISPRUDENCE.

PMID- 18736808
TI  - Amputations and Their After Treatment.

PMID- 18736809
TI  - Clinical Records: II. Blank Forms.

PMID- 18736810
TI  - The Application of Anoci Association to Obstetrics.

PMID- 18736811
TI  - The Treatment of Congenital Syphilis.

PMID- 18736812
TI  - Routine Radiological Demonstration of Gall-Stones.

PMID- 18736813
TI  - Dr. Carlos J. Finlay: Discoverer of the Theory of the Transmission of Yellow
      Fever by the Mosquito, His Biography.

PMID- 18736815
TI  - Which is the Preferable Operation, Perineal or Suprapubic Prostatectomy?

PMID- 18736814
TI  - The Use of the X-Ray as an Aid in Surgical Operations.

PMID- 18736816
TI  - TWILIGHT SLEEP.

PMID- 18736817
TI  - GLANDULAR POLYPUS OF THE COLON.

PMID- 18736818
TI  - SOCIETY REPORTS.

PMID- 18736819
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736820
TI  - THE AUTOLYSIN TREATMENT OF CANCER.

PMID- 18736821
TI  - PEACHES PEELED BY LYE NOT INJURIOUS TO HEALTH.

PMID- 18736822
TI  - JOURNAL OF CUTANEOUS DISEASES.

PMID- 18736824
TI  - FULL-TIME HEALTH OFFICERS.

PMID- 18736823
TI  - THE COMMANDMENTS GOVERNING THE RELATIONS OF THE PUBLIC WITH THE DOCTOR.

PMID- 18736826
TI  - 1916.

PMID- 18736825
TI  - A CLINICAL PILGRIMAGE IN WAR-TIME.

PMID- 18736828
TI  - CLINICAL RECORDS: III. THE LATER CLINICAL NOTES AND LIST OF ABBREVIATIONS.

PMID- 18736827
TI  - STATE SOCIETY-FRESNO, APRIL 18, 19, 20, 1916.

PMID- 18736829
TI  - PERINEPHRITIC ABSCESSES.

PMID- 18736830
TI  - THE NEED OF PSYCHOPATHIC HOSPITALS IN LARGE CITIES: With Illustrative Cases.

PMID- 18736831
TI  - DR. WILLIAM OPHULS, DEAN.

PMID- 18736832
TI  - DR. MOLONY AND "THE HOG-TIGHT FENCE".

PMID- 18736833
TI  - FRACTURE RECORDS.

PMID- 18736834
TI  - AMERICAN MEDICAL DIRECTORY.

PMID- 18736835
TI  - ARE WE MAKING PROGRESS IN THE EARLY RECOGNITION OF TUBERCULOSIS?

PMID- 18736836
TI  - REVIEW OF RECENT PROGRESS IN X-RAY.

PMID- 18736838
TI  - THE ORIGIN AND ENDING OF THE DR. JORDAN MUSEUM OF ANATOMY, ETC., ETC.

PMID- 18736837
TI  - MASTOID OPERATION DEPENDENT UPON PATHOLOGY.

PMID- 18736839
TI  - IN THE TROUBLED PART OF THE WORLD.

PMID- 18736840
TI  - THE ABDERHALDEN TEST.

PMID- 18736841
TI  - THE "AUTOLYSIN" TREATMENT FOR CANCER.

PMID- 18736842
TI  - OSTEOPATHIC INGENUOUSNESS.

PMID- 18736843
TI  - SOME ADVICE.

PMID- 18736844
TI  - ON HOSPITALS.

PMID- 18736845
TI  - SOCIETY REPORTS.

PMID- 18736846
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736847
TI  - ITEMS OF INTEREST.

PMID- 18736849
TI  - TRACHOMA.

PMID- 18736848
TI  - RED CROSS STAMPS.

PMID- 18736851
TI  - JAPANESE CAREFUL TO REGISTER ALL BIRTHS.

PMID- 18736850
TI  - BOARD OF MEDICAL EXAMINERS.

PMID- 18736853
TI  - STEREOPTICON LOAN LIBRARY.

PMID- 18736852
TI  - THE REPUTATION OF REMEDIES FOR SYPHILIS.

PMID- 18736854
TI  - CAUSE AND CURE OF PELLAGRA.

PMID- 18736856
TI  - NAVY.

PMID- 18736855
TI  - NON-RESIDENT TUBERCULOSIS CASES UNCARED FOR.

PMID- 18736858
TI  - LARYNGEAL DIPHTHERIA; OUR KNOWLEDGE OF IT UP TO DATE.

PMID- 18736857
TI  - VACCINES.

PMID- 18736859
TI  - LOCAL ANESTHETICS.

PMID- 18736860
TI  - FRESNO-1916.

PMID- 18736861
TI  - STATUTES OF LIMITATION.

PMID- 18736862
TI  - THE A. M. A. LAW SUIT!

PMID- 18736863
TI  - PROGRAM COMMITTEE.

PMID- 18736864
TI  - INDIGENT TUBERCULOTICS.

PMID- 18736865
TI  - SOCIAL INSURANCE.

PMID- 18736866
TI  - ABUSE OF THE MAILS BY PHYSICIANS; DANGER!!

PMID- 18736867
TI  - TEST OR ASTROLOGY?

PMID- 18736869
TI  - WHAT WE SHOULD KNOW.

PMID- 18736868
TI  - MILITARY-MEDICAL PREPAREDNESS.

PMID- 18736871
TI  - ANOCI-ASSOCIATION: A PLEA FOR THE SURGICAL PATIENT.

PMID- 18736870
TI  - TRAUMATISM OF THE BRAIN.

PMID- 18736872
TI  - LEUKOPENIA. IT'S RELATION TO ORCHITIS. CASE REPORT.

PMID- 18736874
TI  - IS RABIES UNDER CONTROL IN CALIFORNIA?

PMID- 18736873
TI  - CLINICAL RECORDS.

PMID- 18736875
TI  - THE PROGNOSIS OF PROSTATITIS.

PMID- 18736876
TI  - CRIMINAL ABORTIONS AND THE MEDICAL PROFESSION.

PMID- 18736877
TI  - THE RESULTS OF THIRTY-FIVE TRANSFUSIONS.

PMID- 18736878
TI  - THE PHYSICIAN AND THE ADOPTION LAW IN THE STATE OF CALIFORNIA.

PMID- 18736879
TI  - SOCIETY REPORTS.

PMID- 18736881
TI  - THE OATH OF HIPPOCRATES.

PMID- 18736880
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736882
TI  - ITEMS OF INTEREST.

PMID- 18736883
TI  - THE FACTOR OF POVERTY IN SANITATION.

PMID- 18736885
TI  - "KIDNEY CURES" SEIZED.

PMID- 18736884
TI  - CO-OPERATION IN INDUSTRIAL HEALTH INSURANCE LEGISLATION.

PMID- 18736886
TI  - REPORT OF INDUSTRIAL ACCIDENT COMMISSION.

PMID- 18736887
TI  - INDIGENT TUBERCULOTICS.

PMID- 18736888
TI  - SUMMARY OF THE ANNUAL REPORT OF THE SURGEON-GENERAL OF THE UNITED STATES PUBLIC
      HEALTH SERVICE.

PMID- 18736890
TI  - CARELESSNESS AND ACCIDENTS.

PMID- 18736889
TI  - UNITED STATES PUBLIC HEALTH SERVICE.

PMID- 18736892
TI  - CONCRETIONS OF THE SPLEEN.

PMID- 18736891
TI  - DEPARTMENT OF PSYCHOLOGY IN LOS ANGELES CITY SCHOOLS-A STUDY OF THE MENTALLY
      DIFFERENT.

PMID- 18736893
TI  - LEUKOPENIA: ITS RELATION TO NEURALGIA.

PMID- 18736894
TI  - TENTATIVE PROGRAM OF EYE, EAR, NOSE AND THROAT SECTION.

PMID- 18736895
TI  - THE TYPHOID FEVER DEATH RATE IN CALIFORNIA.

PMID- 18736896
TI  - ORAL HYGIENE-THE CARE OF THE MOUTH DURING ILLNESS.

PMID- 18736898
TI  - CASE REPORTS.

PMID- 18736897
TI  - COMPLETE REMOVAL OF PAROTID GLAND WITHOUT INJURY TO FACIAL NERVE.

PMID- 18736899
TI  - SOCIETY REPORTS.

PMID- 18736900
TI  - DR. ROSE TALBOTT BULLARD.

PMID- 18736901
TI  - DR. G. I. CASON.

PMID- 18736902
TI  - SAFETY FIRST.

PMID- 18736903
TI  - AMERICAN FIRST AID CONFERENCE.

PMID- 18736904
TI  - TO TELL RECENT VICTORIES IN WAR ON TROPICAL DISEASES.

PMID- 18736906
TI  - STATE SOCIETY MEETING, APRIL 1916. FRESNO!! FRESNO!! FRESNO!!

PMID- 18736905
TI  - YOUR OFFICE.

PMID- 18736907
TI  - TUBERCULOSIS.

PMID- 18736908
TI  - YOUTHFUL PARENT; ORDINARY CHILD.

PMID- 18736909
TI  - OPERATIONS AND THE LAW.

PMID- 18736910
TI  - POISONOUS FLY PAPERS.

PMID- 18736911
TI  - OBSTETRICS AND MALPRACTICE SUITS.

PMID- 18736912
TI  - HOSPITAL LIABILITIES.

PMID- 18736913
TI  - REPORTS ARE TO BE MADE, NOT ASSUMED.

PMID- 18736915
TI  - CLINICAL RECORDS: V. THE GENERAL OVERSIGHT AND FILING OF RECORDS.

PMID- 18736914
TI  - SOUTHERN PACIFIC.

PMID- 18736916
TI  - CASE RECORDING.

PMID- 18736918
TI  - FRESNO MEETING, APRIL 18, 19, 20.

PMID- 18736917
TI  - A STUDY IN HANDICAPS.

PMID- 18736919
TI  - "FRESNO" 1916.

PMID- 18736920
TI  - MEDICAL DEFENSE AND INSURANCE COMPANIES.

PMID- 18736922
TI  - CO-OPERATION WITH INSURANCE COMPANY.

PMID- 18736921
TI  - ORANGE COUNTY AND MEDICAL DEFENSE.

PMID- 18736924
TI  - MEMBERSHIP.

PMID- 18736923
TI  - ACCOUNTS.

PMID- 18736926
TI  - AUTOMOBOLISTS ATTENTION!: TO FRESNO BY AUTOMOBILE.

PMID- 18736925
TI  - CURIOUS, TO SAY THE LEAST!

PMID- 18736927
TI  - REPORT OF CASES OF MALIGNANT TESTICLE.

PMID- 18736928
TI  - A WATER-BORNE EPIDEMIC OF TYPHOID FEVER AT SANTA BARBARA.

PMID- 18736929
TI  - PERSONAL EXPERIENCES WITH ROENTGEN RAYS IN GYNECOLOGIC PRACTICE.

PMID- 18736930
TI  - BOTULISM: ITS OCCURRENCE IN CALIFORNIA.

PMID- 18736931
TI  - DIAGNOSIS OF MALARIA.

PMID- 18736932
TI  - AN ARTHROPLASTY OF THE ELBOW.

PMID- 18736933
TI  - REPORT OF CASE.

PMID- 18736934
TI  - THE URGENT NEED FOR A MORE ADEQUATE TREATMENT OF SYPHILIS.

PMID- 18736936
TI  - ITEMS OF INTEREST.

PMID- 18736937
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736935
TI  - SOCIETY REPORTS.

PMID- 18736938
TI  - GOVERNMENT OPENS A FREE EMPLOYMENT BUREAU FOR FARMERS AND OTHERS SEEKING HELP IN
      SAN FRANCISCO.

PMID- 18736939
TI  - IT PAYS THE MANUFACTURER TO MAINTAIN ETHICAL STANDARDS.

PMID- 18736941
TI  - THE FRESNO MEETING.

PMID- 18736940
TI  - IN RE: RESOLUTIONS OF ENDORSEMENT OF CALIFORNIA STATE BOARD OF MEDICAL EXAMINERS,
      AND OF DR. WM. R. MOLONY OF LOS ANGELES.

PMID- 18736942
TI  - OUR LIBEL SUIT.

PMID- 18736943
TI  - VIAVI AND THE UNIVERSITY OF CALIFORNIA.

PMID- 18736945
TI  - NEW AND NON-OFFICIAL REMEDIES.

PMID- 18736944
TI  - RECORDS.

PMID- 18736947
TI  - DR. BLOODGOOD AND CANCER.

PMID- 18736946
TI  - TAKE WARNING! HEALTH INSURANCE.

PMID- 18736948
TI  - WAIVER OF PRIVILEGE.

PMID- 18736949
TI  - THE HARVEST OF THE REAPER.

PMID- 18736950
TI  - HEALTH AND THE WOMAN MOVEMENT.

PMID- 18736951
TI  - PROPER FOOD FOR YOUNG CHILDREN.

PMID- 18736952
TI  - INDUSTRIAL ACCIDENT INSURANCE.

PMID- 18736954
TI  - POST-MORTEM EXAMINATIONS.

PMID- 18736953
TI  - SUBSCRIPTION SWINDLERS.

PMID- 18736955
TI  - SOCIAL INSURANCE: From the New York State Journal of Medicine.

PMID- 18736956
TI  - ADEQUATE INSTITUTIONAL CARE OF THE TUBERCULAR.

PMID- 18736957
TI  - COURSE OF FRESH SYPHILIS AS TREATED BY THE NEWER REMEDIES.

PMID- 18736959
TI  - FRESH SYPHILIS AND THE NEWER REMEDIES.

PMID- 18736958
TI  - REMARKS ON THE MODERN TREATMENT OF SYPHILIS.

PMID- 18736960
TI  - THE TREATMENT OF SYPHILIS IN THE PRIMARY STAGE.

PMID- 18736962
TI  - ATTENTION! PHYSICIANS AND DENTISTS.

PMID- 18736961
TI  - THE PRESENT STATUS OF SALVARSAN TREATMENT.

PMID- 18736963
TI  - THE INCONSPICUOUS, EVERY-DAY FORMS OF THYROID INSUFFICIENCY.

PMID- 18736964
TI  - ORAL HYGIENE FROM AN EDUCATIONAL AND ECONOMIC VIEWPOINT.

PMID- 18736965
TI  - PRE- AND POST-OPERATIVE CARE.

PMID- 18736966
TI  - NATIONAL QUARANTINE AND ITS FUNCTION.

PMID- 18736967
TI  - WHY CORRECTIVE LENSES OFTEN FAIL TO GIVE RELIEF IN HEADACHES DUE TO EYE-STRAIN.

PMID- 18736968
TI  - RUBEOLA.

PMID- 18736969
TI  - PLASMODIUM MALARIAE (QUARTAN)-A TYPE NEW TO CALIFORNIA: Report of two cases.

PMID- 18736970
TI  - SLOW POISONING BY "CHRISTIAN SCIENCE.": Report of Caesarian Section on a subject
      of Myxaedema of fourteen years' duration with living mother and child which was
      born a Cretin.

PMID- 18736971
TI  - SOCIETY REPORTS.

PMID- 18736972
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18736974
TI  - PRINCIPAL CAUSES OF DEATH: Census Bureau's Summary of the Statistics for the
      Registration Area in 1914.

PMID- 18736973
TI  - A PLEA FOR CERTAIN MEDICAL OFFICERS OF THE U. S. ARMY.

PMID- 18736975
TI  - RAILROAD "DAYS.".

PMID- 18736976
TI  - PNEUMONIA.

PMID- 18736977
TI  - IN ERRATA.

PMID- 18736978
TI  - PASO ROBLES.

PMID- 18736979
TI  - CALIFORNIA SPRINGS.

PMID- 18736980
TI  - POORLY QUALIFIED.

PMID- 18736981
TI  - BREACH OF CONTRACT.

PMID- 18736983
TI  - SOCIAL OR HEALTH INSURANCE.

PMID- 18736982
TI  - DIFFICULT SITUATION.

PMID- 18736984
TI  - FIRST AID COMMITTEE.

PMID- 18736985
TI  - THE "PRACTICAL NURSE" AGAIN.

PMID- 18736986
TI  - MANY THANKS!

PMID- 18736987
TI  - A. M. A. LIBEL SUIT.

PMID- 18736988
TI  - A. M. A. DIRECTORY.

PMID- 18736989
TI  - HELPFUL SUGGESTIONS.

PMID- 18736990
TI  - OWNERSHIP OF X-RAY PLATES.

PMID- 18736991
TI  - SPLENDID WORK.

PMID- 18736992
TI  - SANITARY ENGINEERING.

PMID- 18736993
TI  - BILLS AGAINST AN ESTATE.

PMID- 18736994
TI  - SCIENTIFIC ANACHRONISM.

PMID- 18736995
TI  - ADDRESS OF THE PRESIDENT.

PMID- 18736996
TI  - THE CONSERVATION OF VISION.

PMID- 18736997
TI  - HUMAN CASES OF RABIES IN CALIFORNIA AND THEIR TREATMENT.

PMID- 18736998
TI  - THE CONSERVATIVE TREATMENT OF FRACTURES OF THE LONG BONES AND OF WOUNDS
      COMPLICATING THEM-A PAPER IN ORTHOPEDIC SURGERY.

PMID- 18736999
TI  - LARGE CYSTS IN THE BLADDER.

PMID- 18737000
TI  - A BRIEF REFERENCE TO THE BACTERIOLOGY OF NASAL SINUS DISEASES.

PMID- 18737001
TI  - TWENTY-SEVEN TRANSFUSIONS AT ST. LUKE'S HOSPITAL.

PMID- 18737002
TI  - A CONSIDERATION OF SOME NEUROLOGICAL CONDITIONS IN CHILDREN.

PMID- 18737003
TI  - POVERTY AND TUBERCULOSIS.

PMID- 18737004
TI  - OWNERSHIP OF THE ROENTGEN RAY PLATES: From the Law Department, A. M. A.

PMID- 18737005
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18737006
TI  - A TUBERCULOSIS STORY.

PMID- 18737008
TI  - SACRAMENTO COUNTY.

PMID- 18737007
TI  - ANOTHER RAP AT THE PUBLIC HEALTH DEPARTMENT: From the Journal of Maine Medical
      Association.

PMID- 18737009
TI  - DINING CARS.

PMID- 18737011
TI  - MRS. REINHARDT.

PMID- 18737010
TI  - MEDICAL MEN OPEN HEALTH INSURANCE CAMPAIGN.

PMID- 18737013
TI  - HAY-FEVER WEEDS AND HOW THEY MAY BE RECOGNIZED.

PMID- 18737012
TI  - OUTLINE OF POSSIBLE METHODS FOR THE ORGANIZATION OF MEDICAL SERVICE UNDER HEALTH
      INSURANCE.

PMID- 18737014
TI  - BIRTH REGISTRATION IN SAN FRANCISCO.

PMID- 18737015
TI  - SAFETY AT REASONABLE COST.

PMID- 18737016
TI  - PAYING JUDGMENTS.

PMID- 18737017
TI  - MALPRACTICE DEFENSE.

PMID- 18737019
TI  - THE OPPORTUNITY IS YOURS.

PMID- 18737018
TI  - ACT QUICKLY.

PMID- 18737021
TI  - A BUSINESS PROPOSITION.

PMID- 18737020
TI  - NOT ONLY SURGEONS.

PMID- 18737022
TI  - THE HARRISON NARCOTIC LAW.

PMID- 18737023
TI  - THE VALUE OF A MEDICAL LICENSE IN CALIFORNIA.

PMID- 18737024
TI  - HEALTH INSURANCE.

PMID- 18737025
TI  - HEALTH EFFICIENCY.

PMID- 18737026
TI  - CORRECTION.

PMID- 18737027
TI  - SOCIAL INSURANCE.

PMID- 18737028
TI  - "SCIENCE"-?

PMID- 18737029
TI  - EXPERTS IN OUR MALPRACTICE CASES.

PMID- 18737030
TI  - COUNTY SOCIETY ACTIVITY.

PMID- 18737032
TI  - ANOTHER SWINDLER.

PMID- 18737031
TI  - SECOND THOUGHTS ABOUT SALVARSAN THERAPY.

PMID- 18737033
TI  - NEW VIEWS ON TUBERCULOSIS.

PMID- 18737034
TI  - CHRONIC APPENDICITIS COMPLICATING PULMONARY TUBERCULOSIS.

PMID- 18737035
TI  - NOTES ON SYPHILIS OF THE CENTRAL NERVOUS SYSTEM.

PMID- 18737036
TI  - ROUTES OF INFECTION IN TUBERCULOSIS.

PMID- 18737037
TI  - A STATISTICAL STUDY OF RABIES IN CALIFORNIA.

PMID- 18737038
TI  - DANGER OF BATHS IN PATIENTS SUFFERING FROM ARTERIO-SCLEROSIS.

PMID- 18737039
TI  - TUBERCULIN THERAPY: ITS PRINCIPLES, LIMITATIONS AND INDICATIONS.

PMID- 18737040
TI  - SIMPLE TREATMENT OF FRACTURE OF INFERIOR MAXILLA.

PMID- 18737041
TI  - FRACTURE OF THE BASE OF SKULL; PRESENTATION OF PATIENT.

PMID- 18737042
TI  - ROENTGEN TREATMENT OF GOITRE.

PMID- 18737043
TI  - THE CONSERVATIVE TREATMENT OF FRACTURES OF THE LONG BONES AND OF WOUNDS
      COMPLICATING THEM-A PAPER IN ORTHOPEDIC SURGERY.

PMID- 18737044
TI  - SOCIETY REPORTS.

PMID- 18737045
TI  - WARNING.

PMID- 18737047
TI  - POSTAL SAVINGS.

PMID- 18737046
TI  - STATE DESTROYS MILLION POUNDS OF FOOD.

PMID- 18737048
TI  - SOCIAL INSURANCE.

PMID- 18737049
TI  - CARELESS AUTOMOBILISTS.

PMID- 18737050
TI  - WAR DEPARTMENT.

PMID- 18737051
TI  - ARMY MEDICAL CORPS EXAMINATIONS.

PMID- 18737052
TI  - NEW SECTIONS.

PMID- 18737053
TI  - MEDICINE AND DENTISTRY: First University Dental School in New York for Columbia.

PMID- 18737054
TI  - THE SAMUEL D. GROSS PRIZE, FIFTEEN HUNDRED DOLLARS: Essays Will Be Received in
      Competition for the Prize Until January 1st, 1920.

PMID- 18737055
TI  - HEALTH EFFICIENCY.

PMID- 18737056
TI  - THE VERDICT AGAINST THE A. M. A.

PMID- 18737058
TI  - SOCIAL INSURANCE.

PMID- 18737057
TI  - X-RAY PLATES AND NEGLIGENCE.

PMID- 18737059
TI  - WHEN YOU SUE AN ESTATE FOR YOUR ACCOUNT.

PMID- 18737060
TI  - WHAT WE DO NOT KNOW.

PMID- 18737062
TI  - THE PREPAREDNESS PARADE.

PMID- 18737061
TI  - FOURTH OF JULY.

PMID- 18737063
TI  - ETIOLOGY OF OZENA.

PMID- 18737064
TI  - INFANTILE PARALYSIS.

PMID- 18737065
TI  - FEES UNDER THE INDUSTRIAL ACCIDENT LAW.

PMID- 18737067
TI  - THE "SCIENTIFIC" AMERICAN.

PMID- 18737068
TI  - THE HARRISON LAW.

PMID- 18737069
TI  - HEALTH INSURANCE.

PMID- 18737070
TI  - DOCTOR CORNELIUS VAN ZWALENBURG.

PMID- 18737072
TI  - DOCTOR GEORGE L. PAINTER.

PMID- 18737071
TI  - THE PASSING OF THE BONE PLATE.

PMID- 18737073
TI  - CONTRACTURE OF THE VESICAL NECK. DIAGNOSIS AND TREATMENT.

PMID- 18737074
TI  - CONGENITAL PYLORIC STENOSIS.

PMID- 18737075
TI  - PRELIMINARY TESTS OF THE BLOOD IN TRANSFUSIONS.

PMID- 18737076
TI  - LEUKOPENIA, ITS RELATION TO BRONCHITIS.

PMID- 18737077
TI  - PROSPECTS OF SURGICAL TREATMENT IN MENINGITIS.

PMID- 18737078
TI  - TREATMENT OF DIPHTHERIA.

PMID- 18737080
TI  - NEW SAN FRANCISCO HOSPITAL.

PMID- 18737079
TI  - PSYCHOGENIC FACTORS IN ORGANIC DISEASE: Illustrated by two cases.

PMID- 18737082
TI  - SOCIETY REPORTS.

PMID- 18737081
TI  - EPIDEMIC CEREBRO-SPINAL MENINGITIS: Report of Case with Interesting
      Complications.

PMID- 18737083
TI  - ACUTE ANTERIOR POLIOMYELITIS. (INFANTILE PARALYSIS).

PMID- 18737084
TI  - Correspondence.

PMID- 18737085
TI  - STATE JOURNALS AND ADVERTISING.

PMID- 18737086
TI  - STATE JOURNALS AND ADVERTISING.

PMID- 18737087
TI  - TUBERCULOSIS MEETING.

PMID- 18737088
TI  - MALPRACTICE INDEMNITY FUND.

PMID- 18737089
TI  - PROGRAM COMMITTEE.

PMID- 18737090
TI  - CARELESS DOCTORS.

PMID- 18737091
TI  - GRIEVANCE COMMITTEE.

PMID- 18737092
TI  - IN SUPPORT OF HEALTH INSURANCE.

PMID- 18737093
TI  - MALPRACTICE RULES.

PMID- 18737094
TI  - INFANT MORTALITY.

PMID- 18737095
TI  - WARNING!

PMID- 18737097
TI  - PURELY PERSONAL.

PMID- 18737096
TI  - SCIENTIFIC AMERICAN.

PMID- 18737098
TI  - CULTIVATION OF VACANT LOTS.

PMID- 18737099
TI  - GEORGE L. PAINTER, M. D.

PMID- 18737100
TI  - THE VALUE OF FUCHSIN IN UROLOGY.

PMID- 18737101
TI  - INDUSTRIAL HERNIA.

PMID- 18737102
TI  - DIAGNOSIS AND TREATMENT OF POLIOMYELITIS IN THE PREPARALYTIC STAGE.

PMID- 18737103
TI  - THE REMOVAL OF FOREIGN BODIES FROM THE ESOPHAGUS AND RESPIRATORY TRACT.

PMID- 18737105
TI  - APOCODEIN-A NEW LAXATIVE WITH EXCEPTIONAL ADVANTAGES.

PMID- 18737104
TI  - PERIODONTAL SEPTIC FOCI.

PMID- 18737106
TI  - THE PATHOLOGICAL ANATOMY, SYMPTOMS AND DIAGNOSIS OF RENAL TUBERCULOSIS.

PMID- 18737107
TI  - THE HISTORY IN GROUP STUDY: A Summary of One Hundred Case Histories.

PMID- 18737108
TI  - RETRODISPLACEMENTS OF THE UTERUS, WITH ESPECIAL REFERENCE TO THEIR CAUSATION AND
      A NEW METHOD OF TREATMENT.

PMID- 18737109
TI  - DISCUSSION OF THE PATHOLOGICAL DIVISION OF ST. LUKE'S HOSPITAL CLINICAL CLUB.

PMID- 18737110
TI  - A BRIEF REFERENCE TO THE BACTERIOLOGY OF NASAL SINUS DISEASES.

PMID- 18737111
TI  - SOCIETY REPORTS.

PMID- 18737113
TI  - INDUSTRIAL WELFARE NUMBER OF "THE MODERN HOSPITAL".

PMID- 18737112
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18737115
TI  - A NOTABLE PATENT MEDICINE SUIT.

PMID- 18737114
TI  - THE PHYSICIAN'S HEALTH AND ACCIDENT INSURANCE COMPANY OF CALIFORNIA.

PMID- 18737117
TI  - MEDICAL PREPAREDNESS LEAGUE.

PMID- 18737116
TI  - NAVY SURGEONS.

PMID- 18737118
TI  - INDEMNITY FUND.

PMID- 18737119
TI  - ANNUAL MEETING AT CORONADO.

PMID- 18737120
TI  - IMPORTANT NOTICE.

PMID- 18737121
TI  - INDUSTRIAL ACCIDENT INSURANCE.

PMID- 18737122
TI  - CHANGES IN MEDICINE.

PMID- 18737124
TI  - HEALTH INSURANCE.

PMID- 18737123
TI  - SOCIAL INSURANCE.

PMID- 18737125
TI  - STANDARD LABORATORY TESTS.

PMID- 18737126
TI  - IDENTIFYING RECORDS.

PMID- 18737128
TI  - STATUTE OF LIMITATIONS.

PMID- 18737127
TI  - HOSPITAL CHARTS.

PMID- 18737130
TI  - BRIEF FOR HEALTH INSURANCE.

PMID- 18737129
TI  - THE PAYING OF THE OLD MORTGAGE ON ST. LUKE'S HOSPITAL.

PMID- 18737132
TI  - INFECTION-PSYCHOSES AND THE SYMPTOM-PICTURE OF MENTAL CONFUSION.

PMID- 18737131
TI  - POLIOMYELITIS.

PMID- 18737133
TI  - SELECTED POINTS IN GASTRO-INTESTINAL DIAGNOSIS.

PMID- 18737135
TI  - ROCKY MOUNTAIN SPOTTED FEVER-ITS PREVALENCE AND DISTRIBUTION IN MODOC AND LASSEN
      COUNTIES, CALIFORNIA-A PRELIMINARY REPORT.

PMID- 18737134
TI  - SEPTIC TEETH.

PMID- 18737136
TI  - THE CONSIDERATION OF RECTAL AND COLONIC DISEASE IN LIFE INSURANCE EXAMINATIONS.

PMID- 18737137
TI  - RESUME OF EPIDEMIOLOGICAL INVESTIGATIONS OF EPIDEMICS OF POLIOMYELITIS WITH
      REFERENCE TO CONTAGIOUSNESS.

PMID- 18737138
TI  - SIR VICTOR HORSLEY: An Appreciation.

PMID- 18737139
TI  - FEDERAL SUPERVISION AND LICENSURE OF CLINICAL LABORATORIES UNDER THE POSTAL
      REGULATIONS-A PUBLIC HEALTH MEASURE.

PMID- 18737141
TI  - SOCIETY REPORTS.

PMID- 18737140
TI  - THE REMOVAL OF FOREIGN BODIES FROM THE ESOPHAGUS AND RESPIRATORY TRACT.

PMID- 18737142
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18737143
TI  - DANGERS OTHER THAN ACCIDENTS IN THE MAUFACTURE OF EXPLOSIVES.

PMID- 18737144
TI  - UNITED STATES PUBLIC HEALTH SERVICE.

PMID- 18737145
TI  - THE ORGANIZATION OF THE ARMY: Line and Staff, and the Administrative Zones in
      War.

PMID- 18737146
TI  - INDUSTRIAL ACCIDENTS.

PMID- 18737147
TI  - INCREASED COSTS.

PMID- 18737149
TI  - ANNUAL MEETING AT CORONADO.

PMID- 18737148
TI  - MALPRACTICE; A CURIOUS COINCIDENCE.

PMID- 18737150
TI  - THE INDEMNITY FUND.

PMID- 18737152
TI  - CARREL'S SOLUTION.

PMID- 18737151
TI  - IMPORTANT NOTICE: SCIENTIFIC PROGRAM.

PMID- 18737153
TI  - ALCOHOL AND PROHIBITION.

PMID- 18737154
TI  - POST-GRADUATE SCHOOL.

PMID- 18737155
TI  - USEFUL DRUGS.

PMID- 18737156
TI  - SWINDLERS.

PMID- 18737157
TI  - SCIENTIFIC ACTIVITY.

PMID- 18737158
TI  - PHILIP MILLS JONES, ATTORNEY.

PMID- 18737159
TI  - STATE PASTEURIZATION OF MILK.

PMID- 18737160
TI  - REPRINTS.

PMID- 18737161
TI  - THE HEALTH OF SACRAMENTO.

PMID- 18737162
TI  - $5000 VERDICT-HOW WOULD YOU LIKE IT?

PMID- 18737163
TI  - COOPERATIVE MEDICINE IN RELATION TO SOCIAL INSURANCE.

PMID- 18737164
TI  - SHOULD THE MEDICAL PROFESSION PLEAD IN FAVOR OF THE PROPOSED HEALTH INSURANCE
      BILL?

PMID- 18737165
TI  - THE PROPOSED SOCIAL HEALTH INSURANCE ACT.

PMID- 18737166
TI  - ABORTION, AND SOME SUGGESTIONS HOW TO LESSEN CRIMINAL ABORTIONS.

PMID- 18737167
TI  - UPON THE SERO-DIAGNOSIS OF GONORRHEA.

PMID- 18737168
TI  - SEPTIC TEETH.

PMID- 18737170
TI  - ITEMS OF INTEREST.

PMID- 18737169
TI  - SOCIETY REPORTS.

PMID- 18737172
TI  - ARMY MEDICAL CORPS EXAMINATION.

PMID- 18737171
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18737174
TI  - LECTURES ON MEDICAL PREPAREDNESS.

PMID- 18737173
TI  - DENTAL PREPAREDNESS.

PMID- 18737176
TI  - ABOUT INCOMES.

PMID- 18737175
TI  - AGAIN THE INDEMNITY FUND.

PMID- 18737177
TI  - INDEMNITY FUND.

PMID- 18737178
TI  - MALPRACTISE INDEMNITY FUND.

PMID- 18737179
TI  - SOCIAL INSURANCE COMMISSION.

PMID- 18737180
TI  - NEEDED REFORM OF COUNTY SOCIETIES.

PMID- 18737182
TI  - MEDICINE AND SOCIOLOGY.

PMID- 18737181
TI  - MERRY CHRISTMAS!

PMID- 18737184
TI  - SAD BUT TRUE.

PMID- 18737183
TI  - THE EMANUEL MOVEMENT AND THE LAW.

PMID- 18737185
TI  - INDUSTRIAL ACCIDENT INSURANCE.

PMID- 18737186
TI  - PRINCIPLES AND PROBLEMS OF INDUSTRIAL ACCIDENT WORK.

PMID- 18737187
TI  - STUPIDITY.

PMID- 18737188
TI  - INVESTIGATION OF TRAINING SCHOOLS.

PMID- 18737189
TI  - STREPTOCOCCIC INFECTIONS OF THE SKIN.

PMID- 18737190
TI  - FIBROMYOMA UTERI; SKETCH OF TREATMENT, OPERATIVE AND OTHERWISE, WITH SPECIAL
      REFERENCE TO ROENTGEN RAY THERAPY.

PMID- 18737192
TI  - SALVARSAN AND NEOSALVARSAN IN TROPICAL DISEASES.

PMID- 18737191
TI  - INCIPIENT SYSTEMIC DISTURBANCES AS SHOWN BY OCULAR SIGNS.

PMID- 18737193
TI  - SUPPLEMENTARY REPORT OF HUMAN CASES OF RABIES IN CALIFORNIA.

PMID- 18737194
TI  - RECENT WORK IN EPILEPSY.

PMID- 18737195
TI  - ROENTGEN TREATMENT OF LOCALIZED PYOGENIC INFECTIONS WITH REPORT OF EIGHT CASES.

PMID- 18737197
TI  - STATUS AND STANDARDS OF DISPENSARY PRACTICE.

PMID- 18737196
TI  - TWO FREAK ACCIDENTS DURING TONSILLECTOMIES.

PMID- 18737199
TI  - SOCIETY REPORTS.

PMID- 18737198
TI  - SUPPLEMENTARY NOTE TO THE ARTICLE ON "BLINDNESS FOLLOWING INJURIES TO THE BACK OF
      THE HEAD.".

PMID- 18737200
TI  - INTERESTING RELIC.

PMID- 18737201
TI  - ITEMS OF INTEREST.

PMID- 18737202
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18737203
TI  - LEAD IN "AKOZ.".

PMID- 18737204
TI  - Correspondence.

PMID- 18737206
TI  - DOCTOR PHILIP MILLS JONES.

PMID- 18737205
TI  - NAVY SURGEONS.

PMID- 18737207
TI  - THE LEGISLATURE MEETS SOON.

PMID- 18737208
TI  - MALPRACTICE INDEMNITY FUND.

PMID- 18737209
TI  - DOCTOR PHILIP MILLS JONES.

PMID- 18737210
TI  - DIABETES IN PREGNANCY, WITH REPORT OF CASES.

PMID- 18737211
TI  - USE OF WHOLE BLOOD IN HEMORRHAGE.

PMID- 18737213
TI  - OBSCURE SYMPTOMS OF RHEUMATISM IN CHILDREN.

PMID- 18737212
TI  - THE ATTITUDE OF THE PHYSICIAN TOWARD THE VENEREAL PATIENT.

PMID- 18737214
TI  - ON PATIENTS.

PMID- 18737215
TI  - AND THEIR RECORDS.

PMID- 18737216
TI  - MEDICINE AND PHYSIOLOGY.

PMID- 18737217
TI  - THE TREATMENT OF FRACTURES OF LONG BONES.

PMID- 18737218
TI  - A TRIAL OF GOODMAN'S "AUTOSERUM" TREATMENT OF CHOREA.

PMID- 18737220
TI  - HEALTH INSURANCE.

PMID- 18737219
TI  - TYPHUS EXANTHEMATICUS IN SAN FRANCISCO.

PMID- 18737222
TI  - SOCIAL INSURANCE COUNTY COMMITTEES.

PMID- 18737221
TI  - WALKING FOR HEALTH.

PMID- 18737223
TI  - SULPHUR AS A REMEDY FOR RHEUMATISM.

PMID- 18737224
TI  - FEES FOR INDUSTRIAL ACCIDENT WORK.

PMID- 18737225
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18737226
TI  - DEPARTMENT OF BACTERIOLOGY AND PATHOLOGY.

PMID- 18737227
TI  - ALCOHOL.

PMID- 18737228
TI  - DOCTORS' INCOMES.

PMID- 18737229
TI  - REGULATION OF THE PRACTICE OF MEDICINE. CIRCULAR LETTER SENT TO STATE SENATORS
      AND ASSEMBLYMEN IN 1915.

PMID- 18737231
TI  - DOCTOR PHILIP MILLS JONES.

PMID- 18737230
TI  - FEES FOR INDUSTRIAL ACCIDENT WORK.

PMID- 18737232
TI  - COMMON COLDS.

PMID- 18737233
TI  - THE MEDICAL PRACTICE ACT.

PMID- 18737234
TI  - THE MALPRACTICE INDEMNITY FUND.

PMID- 18737235
TI  - MEDICAL EDUCATION BY NEWSPAPERS.

PMID- 18737236
TI  - A CRYING NEED-A STATE PSYCHOPATHIC HOSPITAL.

PMID- 18737237
TI  - TRAUMA AND ITS SEQUELS.

PMID- 18737238
TI  - THE MEDICAL ASPECT OF COUNTY JAILS.

PMID- 18737240
TI  - THE LEGISLATURE IN SESSION.

PMID- 18737239
TI  - HUMOR IN DIETS.

PMID- 18737241
TI  - SOCIAL INSURANCE.

PMID- 18737242
TI  - ANTI-VIVISECTION.

PMID- 18737243
TI  - THE OPERATIVE TREATMENT OF VERTEBRAL TUBERCULOSIS.

PMID- 18737244
TI  - THE PHYSICIAN'S RESPONSIBILITY TO LIFE INSURANCE.

PMID- 18737245
TI  - THE USE OF PURE CARBOLIC ACID IN SELECTED CASES OF CHRONIC MIDDLE EAR
      SUPPURATION.

PMID- 18737247
TI  - SOCIETY REPORTS.

PMID- 18737246
TI  - UPON THE RADIOGRAPHIC DIAGNOSIS OF HYDRONEPHROSIS.

PMID- 18737248
TI  - DEPARTMENT OF BACTERIOLOGY AND PATHOLOGY.

PMID- 18737249
TI  - HYGIENE AND SANITATION ON OCEAN VESSELS.

PMID- 18737250
TI  - A BILL FOR THE PROMOTION OF MEDICAL RESEARCH.

PMID- 18737252
TI  - TRAINING-SCHOOLS FOR NURSES.

PMID- 18737251
TI  - MEDICAL LEGISLATION.

PMID- 18737254
TI  - OLEOMARGARINE OR BUTTER.

PMID- 18737253
TI  - A FOOL THERE WAS.

PMID- 18737256
TI  - A REPORT OF FIFTY CASES OF TUBERCULOSIS OF THE KIDNEY AND BLADDER CLINICALLY
      CURED WITHOUT OPERATION.

PMID- 18737255
TI  - ANIMAL EXPERIMENTATION AND MEDICAL PROGRESS.-AN ARGUMENT IN SUPPORT OF A BILL NOW
      BEFORE THE STATE LEGISLATURE.

PMID- 18737257
TI  - TREATMENT OF SYPHILIS.

PMID- 18737258
TI  - THE LIMITATIONS OF ROENTGENOLOGY IN TUMORS OF THE KIDNEY.

PMID- 18737259
TI  - STENOSIS OF THE DUODENUM.

PMID- 18737260
TI  - SOCIETY REPORTS.

PMID- 18737261
TI  - DEPARTMENT OF BACTERIOLOGY AND PATHOLOGY.

PMID- 18737262
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18737263
TI  - ITEMS OF INTEREST.

PMID- 18737264
TI  - DOCTOR WILLIAM WATT KERR: AN APPRECIATION.

PMID- 18737265
TI  - SAN FRANCISCO POLYCLINIC POST-GRADUATE EXTENSION LECTURES.

PMID- 18737266
TI  - McINTIRE PRIZE.

PMID- 18737267
TI  - PROPOSED AMENDMENT TO THE CONSTITUTION OF THE SOCIETY.

PMID- 18737268
TI  - MEDICAL LEGISLATION STILL THREATENING.

PMID- 18737269
TI  - THE CHARTERING OF MEDICAL TEACHING INSTITUTIONS.

PMID- 18737270
TI  - THE PROSECUTION OF QUACKS.

PMID- 18737272
TI  - STUDENTS' HEALTH INSURANCE AT THE UNIVERSITY OF CALIFORNIA.

PMID- 18737271
TI  - GERMAN SALVARSAN AND THE AMERICAN PRODUCT ARSENOBENZOL.

PMID- 18737273
TI  - THE SAN DIEGO DIAGNOSTIC GROUP CLINIC: A PRELIMINARY REPORT.

PMID- 18737274
TI  - SYMPTOMATOLOGY OF HYPERTHYROIDISM.

PMID- 18737275
TI  - TREATMENT OF SYPHILIS.

PMID- 18737277
TI  - Society Reports.

PMID- 18737276
TI  - PROPOSED AMENDMENT TO THE CONSTITUTION OF THE SOCIETY.

PMID- 18737278
TI  - DEPARTMENT OF BACTERIOLOGY AND PATHOLOGY.

PMID- 18737280
TI  - EXAMINATION BY NATIONAL BOARD OF EXAMINERS.

PMID- 18737279
TI  - JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, MARCH 3 and 10, 1917: NATURAL AND
      ACQUIRED RESISTANCE TO TUBERCULOSIS AND BEARING ON PREVENTIVE MEASURES.

PMID- 18737281
TI  - ORGANIZATION OF THE MEDICAL RESERVE CORPS, U. S. ARMY, STATE OF CALIFORNIA.

PMID- 18737282
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18737284
TI  - ARMY MEDICAL CORPS EXAMINATIONS.

PMID- 18737283
TI  - ARMY MEDICAL CORPS EXAMINATIONS.

PMID- 18737286
TI  - THE PHARMACISTS AND PREPAREDNESS.

PMID- 18737285
TI  - FLEECING THE DOCTORS.

PMID- 18737287
TI  - IS IT WORTH WHILE?

PMID- 18737289
TI  - THE JOURNAL AND ITS PROBLEMS.

PMID- 18737288
TI  - THE PROGRAM.

PMID- 18737291
TI  - ON PREPAREDNESS.

PMID- 18737290
TI  - THE JOURNAL OF UROLOGY.

PMID- 18737292
TI  - MOBILIZATION OF MEDICAL RESOURCES.

PMID- 18737293
TI  - THE LEGISLATURE AND MEDICINE.

PMID- 18737294
TI  - RADIUM.

PMID- 18737295
TI  - THE THOUGHTLESS DOCTOR.

PMID- 18737297
TI  - HEALTH INSURANCE.

PMID- 18737296
TI  - DIVISION OF FEES.

PMID- 18737298
TI  - DAY DREAMS.

PMID- 18737299
TI  - HENRY LEBER COIT.

PMID- 18737300
TI  - THE WAR, MEDICAL CULTS, AND THE LONG-SUFFERING DOCTOR.

PMID- 18737301
TI  - BLINDNESS IN THE UNITED STATES.

PMID- 18737302
TI  - Medical Preparedness: Information Regarding the Correlated Activities of the
      Council of National Defense and the Advisory Commission, the Medical Departments
      of Government and the Committee of American Physicians for Medical Prepardedness.

PMID- 18737303
TI  - SOME EPIDEMIOLOGIC AND BACTERIOLOGIC OBSERVATIONS ON PARADYSENTERY INFECTIONS IN
      CALIFORNIA.

PMID- 18737304
TI  - THE SANITARY SERVICe OF WAR AND THE DEMOBILIZATION PERIOD.

PMID- 18737305
TI  - IS ACUTE ANTERIOR POLIOMYELITIS SPREAD BY DIRECT PERSONAL CONTACT?: REPORT OF AN
      INTERSTING INCIDENT.

PMID- 18737306
TI  - THE FALLACY OF POST-VACCINATION TETANUS DUE TO VACCINE VIRUS.

PMID- 18737307
TI  - DEATH DUE TO STATUS LYMPHATICUS FOLLOWING AN INJECTION OF DIPHTHERIA ANTITOXIN.

PMID- 18737308
TI  - TYPHUS FEVER IN CALIFORNIA.

PMID- 18737310
TI  - THREE CASES OF BERIBERI.

PMID- 18737309
TI  - INTESTINAL INFECTION IN THE SACRAMENTO VALLEY.

PMID- 18737311
TI  - THE PREVENTION OF QUARANTINABLE DISEASES ON THE BORDER AND AT PORTS OF
      EMBARKATION.

PMID- 18737312
TI  - ACUTE POLIOMYELITIS WITH SPECIAL REFERENCE TO MYOCLONUS.

PMID- 18737313
TI  - War Department Headquarters Western Department Office of the Department Surgeon.

PMID- 18737315
TI  - Society Reports.

PMID- 18737314
TI  - SYNTHETIC SUBSTITUTES FOR COCAIN WITHDRAWN FROM FEDERAL REGISTRATION.

PMID- 18737316
TI  - DEPARTMENT OF BACTERIOLOGY AND PATHOLOGY.

PMID- 18737317
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18737319
TI  - TETHELIN PRESENTED TO THE UNIVERSITY OF CALIFORNIA BY DOCTOR ROBERTSON.

PMID- 18737318
TI  - THE INDEMNITY DEFENSE FUND.

PMID- 18737320
TI  - MEDICAL DEFENSE RULES AND THE LEGAL DEPARTMENT.

PMID- 18737322
TI  - THE MILITARY SITUATION.

PMID- 18737321
TI  - EXAMINATION OF RECRUITS.

PMID- 18737323
TI  - HAVE YOU ENLISTED?

PMID- 18737324
TI  - THERE BE LAND RATS AND WATER RATS.

PMID- 18737325
TI  - HEALTH INSURANCE.

PMID- 18737326
TI  - UNITED STATES CENSUS BUREAU REPORT ON CANCER.

PMID- 18737328
TI  - AMERICAN REMEDIES FOR CHINESE AILMENTS: BUREAU OF FOREIGN AND DOMESTIC COMMERCE,
      WASHINGTON.

PMID- 18737327
TI  - THE J. HENRY BARBAT PRIZE.

PMID- 18737329
TI  - DR. GEORGE H. KRESS.

PMID- 18737331
TI  - OTITIC MENINGITIS.

PMID- 18737330
TI  - ORGANIZED MEDICINE-A CONSIDERATION OF SOME OF ITS CALIFORNIA PROBLEMS.

PMID- 18737332
TI  - PRESENT AND PROPOSED LEGISLATION FOR THE PREVENTION OF BLINDNESS.

PMID- 18737333
TI  - MENINGITIS OF NASAL ORIGIN.

PMID- 18737334
TI  - ECTOPIC PREGNANCY WITH REPORT OF CASE.

PMID- 18737335
TI  - WILLIAM WATT KERR, M. B., C. M: BORN THE 27TH OF JUNE, 1857, IN EDINBURGH,
      SCOTLAND. DIED THE 26TH OF APRIL, 1917, IN SAN FRANCISCO.

PMID- 18737336
TI  - THE PUBLICATION COMMITTEE.

PMID- 18737337
TI  - THE SAN DIEGO MEETING.

PMID- 18737338
TI  - EXPLANATION OF 1917 AMENDMENTS TO THE MEDICAL PRACTICE ACT.

PMID- 18737340
TI  - DEPARTMENT OF BACTERIOLOGY AND PATHOLOGY.

PMID- 18737339
TI  - Society Reports.

PMID- 18737341
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18737342
TI  - PRELIMINARY PROGRAM, AMERICAN PROCTOLOGIC SOCIETY.

PMID- 18737343
TI  - THE PREPAREDNESS LEAGUE OF AMERICAN DENTISTS.

PMID- 18737344
TI  - DRUGGISTS' COMMISSIONS.

PMID- 18737345
TI  - READ THIS-IT IS FOR YOUR BENEFIT!

PMID- 18737346
TI  - AMERICAN REMEDIES FOR CHINESE AILMENTS.

PMID- 18737347
TI  - MILITARY MEDICAL NEEDS.

PMID- 18737348
TI  - INSURANCE AND THE INDEMNITY DEFENSE FUND.

PMID- 18737349
TI  - OUR LEGAL RECORDS AND THE INDEMNITY DEFENSE FUND.

PMID- 18737350
TI  - THE ALCOHOL QUESTION: I. PHYSIOLOGICAL CONSIDERATIONS.

PMID- 18737351
TI  - A NON-SUTURE OCULAR TENDON SHORTENING WITH RESULTS OF FORTY OPERATIONS.

PMID- 18737353
TI  - GLAUCOMA; A CRITICAL SURVEY OF PRESENT METHODS OF TREATMENT.

PMID- 18737352
TI  - THE PROVOCATIVE WASSERMANN REACTION.

PMID- 18737354
TI  - THE MODERN TREATMENT OF IRITIS.

PMID- 18737356
TI  - TUMORS OF THE KIDNEY.

PMID- 18737355
TI  - THE EARLY SURGICAL TREATMENT OF SQUINT.

PMID- 18737357
TI  - MODERN DIAGNOSIS AND TREATMENT OF NEPHROLITHIASIS.

PMID- 18737358
TI  - ACUTE DILATATION OF THE STOMACH. A REPORT OF SIX CASES, THREE OCCURRING DURING
      ANESTHESIA.

PMID- 18737359
TI  - MERCURIALIZED SERUM INJECTIONS IN SYPHILITIC NERVOUS DISEASES.

PMID- 18737361
TI  - FRACTURES IN WAR TIME.

PMID- 18737360
TI  - THE ECONOMIC IMPORTANCE OF THE WELL POISED PERSON.

PMID- 18737362
TI  - LEUKOPENIA, ITS SIGNIFICANCE.

PMID- 18737363
TI  - SUBDELTOID BURSITIS.

PMID- 18737364
TI  - TWO CASES OF POISONING FROM THE USE OF ALYPIN IN THE URETHRA.

PMID- 18737365
TI  - INDUSTRIAL ACCIDENTS: COMMON INJURIES OF THE EYE AND THEIR TREATMENT.

PMID- 18737366
TI  - OFFICERS RESERVE CORPS AND PENSIONS.

PMID- 18737367
TI  - State Society Notes: Important Notice-To Contributing Members of the Indemnity
      Defense Fund.

PMID- 18737369
TI  - REPORT OF THE TREASURER OF THE COMMITTEE OF AMERICAN PHYSICIANS FOR AID OF THE
      BELGIAN PROFESSION FOR THE QUARTER ENDING MAY 31, 1917.

PMID- 18737368
TI  - Society Reports.

PMID- 18737371
TI  - THE STATE BOARD OF HEALTH MAY MEETING.

PMID- 18737370
TI  - STATE BOARD OF HEALTH, JUNE MEETING.

PMID- 18737373
TI  - THE ALCOHOL QUESTION: II. ALCOHOL AND THE WAR.

PMID- 18737372
TI  - THE RED CROSS.

PMID- 18737374
TI  - MEDICAL WOMEN AND THE WAR.

PMID- 18737375
TI  - THE MEDICAL DEFENSE RULES.

PMID- 18737376
TI  - REGISTRATION FEES.

PMID- 18737377
TI  - EDITORIAL COMMENT.

PMID- 18737378
TI  - SOME HEART PROBLEMS SUGGESTING THE NECESSITY FOR A CLOSER ALLIANCE BETWEEN THE
      PHYSIOLOGISTS, BIO-CHEMISTS AND CLINICIAN.

PMID- 18737379
TI  - SYPHILITIC ARTHRITIS.

PMID- 18737380
TI  - THE TONSILS AS A FOCUS ON INFECTION.

PMID- 18737381
TI  - FOCAL INFECTION INTESTINAL INVOLVEMENT.

PMID- 18737382
TI  - HIGH CALORY FEEDING IN CASES OF TYPHOID FEVER IN CHILDREN.

PMID- 18737383
TI  - CLINICAL OBSERVATIONS OF ONE HUNDRED CASES OF ARTIFICIAL PNEUMOTHORAX.

PMID- 18737384
TI  - TUBERCULOSIS IN CHILDHOOD WITH UNUSUAL MANIFESTATIONS.

PMID- 18737385
TI  - DIFFERENTIAL DIAGNOSIS OF ABDOMINAL TUBERCULOSIS.

PMID- 18737386
TI  - TOXIC GASTRIC HEMORRHAGE.

PMID- 18737387
TI  - HYPOPHYSEAL SYMPTOMATOLOGY; A REVIEW.

PMID- 18737389
TI  - THE GENERAL PRACTITIONER AND THE TUBERCULOUS PATIENT.

PMID- 18737388
TI  - VACCINE IN TYPHOID.

PMID- 18737390
TI  - MEDICAL INSPECTION OF PRISONERS AT SAN QUENTIN WITH REPORT OF CASE OF TINEA
      VERSICOLOR.

PMID- 18737391
TI  - A CASE OF HEMOGLOBINURIA.

PMID- 18737393
TI  - County Societies.

PMID- 18737392
TI  - State Society Notes.

PMID- 18737394
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18737395
TI  - DANGER FROM BOTULISM.

PMID- 18737396
TI  - THE QUOTA OF DOCTORS FOR THE ARMY.

PMID- 18737397
TI  - RED CROSS UNITS.

PMID- 18737398
TI  - THE ALCOHOL QUESTION: III. ALCOHOL A PUBLIC HEALTH PROBLEM.

PMID- 18737399
TI  - EDITORIAL COMMENT.

PMID- 18737400
TI  - SPLENECTOMY IN PERNICIOUS ANEMIA.

PMID- 18737401
TI  - SOME UNUSUAL ASPECTS OF EXOPHTHALMIC GOITER.

PMID- 18737402
TI  - DISABILITY FROM INJURY TO THE FEET.

PMID- 18737403
TI  - THE THERAPEUTIC APPLICATION OF HYPERTONIC SALT-SOLUTION IN CONJUNCTION WITH
      LEUCOCYTIC EXTRACT.

PMID- 18737404
TI  - INTESTINAL CRISES SIMULATING CHRONIC APPENDIX DISEASE DIAGNOSED BY ROENTGEN RAY
      FINDINGS.

PMID- 18737406
TI  - UTERINE FIBROMYOMATA, THEIR CAUSATION, PREVENTION AND CONSERVATIVE TREATMENT: A
      RECORD OF INDIVIDUAL EXPERIENCE.

PMID- 18737405
TI  - ANEURYSM.

PMID- 18737407
TI  - UPON THE MODERN TREATMENT OF BLADDER-TUMORS.

PMID- 18737408
TI  - TUMORS OF THE KIDNEY.

PMID- 18737409
TI  - TREATMENT OF DRUG AND ALCOHOLIC ADDICTIONS.

PMID- 18737410
TI  - THE PATENT MEDICINE EVIL.

PMID- 18737411
TI  - THE ABORTION EVIL IN A SMALL TOWN.

PMID- 18737412
TI  - THE USE OF THE ASPIRATOR FOR REMOVING PUS, BLOOD, EXUDATE, TRANSUDATE, AND BOWEL
      CONTENTS DURING SURGICAL OPERATIONS.

PMID- 18737413
TI  - PRACTICAL X-RAY WORK FOR THE GENERAL PRACTITIONER.

PMID- 18737414
TI  - AN OPEN LETTER.

PMID- 18737415
TI  - NEW SANATORIUM OPENED IN EUREKA.

PMID- 18737416
TI  - A LETTER WORTH READING.

PMID- 18737417
TI  - State Society.

PMID- 18737418
TI  - DEPARTMENT OF PHARMACY AND CHEMISTRY.

PMID- 18737419
TI  - THE CHALLENGING OBLIGATION.

PMID- 18737420
TI  - THE ALCOHOL QUESTION: IV. ECONOMIC CONSIDERATION.

PMID- 18737421
TI  - THE MAINTENANCE OF INDEMNITY DEFENSE FUND.

PMID- 18737422
TI  - NEW MEDICAL PRACTICE LAW.

PMID- 18737423
TI  - THE UNHYGIENIC COLON.

PMID- 18737424
TI  - ACCEPTANCE OF ORIGINAL ARTICLES.

PMID- 18737425
TI  - EDITORIAL COMMENT.

PMID- 18737426
TI  - MALARIA IN RICE FIELDS.

PMID- 18737427
TI  - THE BASIS FOR MEDICAL EXAMINATION IN THE ARMY.

PMID- 18737428
TI  - RECRUITING OBSERVATIONS.

PMID- 18737430
TI  - TREATMENT OF ECLAMPTOGENIC TOXAEMIA OF PREGNANCY WITH SOME CASE REPORTS.

PMID- 18737429
TI  - UROLOGICAL DIAGNOSIS IN GENERAL PRACTICE.

PMID- 18737431
TI  - RADIUM: ITS LOCAL APPLICATION AS A THERAPEUTIC AGENT-WITH CASE REPORTS.

PMID- 18737432
TI  - THE MALARIA PROBLEM IN THE RICE FIELDS.

PMID- 18737433
TI  - COMMON ERRORS IN DIAGNOSIS OF SYPHILIS OF SKIN AND MUCOUS MEMBRANES.

PMID- 18737435
TI  - PROHIBITION AND THE RETURNED SOLDIER; A WORD OF CAUTION.

PMID- 18737434
TI  - THE LATE CORRECTION OF MAL-UNITED FRACTURES OF THE EXTREMITIES.

PMID- 18737437
TI  - Medical Military Matters in California.

PMID- 18737436
TI  - Automobile Coupons.

PMID- 18737438
TI  - State Society.

PMID- 18737439
TI  - State Board of Health: Bureau of Venereal Diseases.

PMID- 18737440
TI  - State Board of Medical Examiners.

PMID- 18737441
TI  - EXTENDING FIELD OF PREVENTIVE MEDICINE.

PMID- 18737442
TI  - PACIFISTS AND HYPHENATES NOT WANTED.

PMID- 18737444
TI  - THE ABSENT DOCTOR'S PRACTICE.

PMID- 18737443
TI  - THE ALCOHOL QUESTION: V. IN CONCLUSION.

PMID- 18737446
TI  - THE RECENT ORAL EXAMINATION OF OSTEOPATHS.

PMID- 18737445
TI  - TYPICAL "NEGLIGENCE" CASES AND SOME REASONS FOR THE FORMATION OF THE INDEMNITY
      DEFENSE FUND.

PMID- 18737447
TI  - CONCERNING CHRISTIAN SCIENCE.

PMID- 18737448
TI  - STATUS OF HEALTH INSURANCE.

PMID- 18737449
TI  - EDITORIAL COMMENT.

PMID- 18737451
TI  - REPORT OF FORTY-FOUR APPENDICITIS OPERATIONS IN CHILDREN UNDER FOURTEEN YEARS OF
      AGE.

PMID- 18737450
TI  - THE VEGETATIVE NERVOUS SYSTEM IN RELATION TO GENERAL MEDICINE.

PMID- 18737452
TI  - INTRA NASAL COSMETIC SURGERY, WITH SPECIAL REFERENCE TO RIB WITH CARTILAGE, AND
      CARTILAGE TRANSPLANTS.

PMID- 18737454
TI  - THE ETIOLOGY OF PELLAGRA.

PMID- 18737455
TI  - MALINGERING; ITS DIAGNOSIS AND SIGNIFICANCE.

PMID- 18737453
TI  - DIAGNOSIS AND TREATMENT OF ACIDOSIS, ESPECIALLY IN DIABETES.

PMID- 18737456
TI  - REMOTE EFFECTS OF BRAIN TRAUMA: SYMPTOMS, COURSE AND PROGNOSIS.

PMID- 18737457
TI  - A REVIEW OF SOME OF THE LATER DEVELOPMENTS ALONG IMMUNOLOGICAL LINES.

PMID- 18737458
TI  - State Society.

PMID- 18737459
TI  - MINIMUM WAGE LAW OUTLINED.

PMID- 18737460
TI  - County Societies.

PMID- 18737461
TI  - Correspondence.

PMID- 18737462
TI  - Correspondence.

PMID- 18737464
TI  - AN OPEN LETTER REPLY.

PMID- 18737463
TI  - Correspondence.

PMID- 18737466
TI  - State Board of Health.

PMID- 18737465
TI  - With the Medical Colleges.

PMID- 18737468
TI  - Department of Pharmacy and Chemistry.

PMID- 18737467
TI  - Quack Chamley Again Active.

PMID- 18737470
TI  - ORAL EXAMINATIONS FOR MEDICAL LICENSES.

PMID- 18737469
TI  - MEDICAL PATRIOTISM AND THE STATE SOCIETY.

PMID- 18737472
TI  - MORE MEDICAL OFFICERS.

PMID- 18737471
TI  - INDEMNITY DEFENSE FUND.

PMID- 18737473
TI  - THE PEOPLE'S COUNCIL.

PMID- 18737474
TI  - EDITORIAL COMMENT.

PMID- 18737475
TI  - A BAD SITUATION.

PMID- 18737477
TI  - SOME PROPERTIES AND ACTIONS OF TETHELIN, THE ACTIVE CONSTITUENT OF THE ANTERIOR
      LOBE OF THE PITUITARY BODY.

PMID- 18737476
TI  - THE DISEASES OF WAR: THEIR PREVENTION, CONTROL AND TREATMENT: THE HANDLING OF
      INFECTIOUS DISEASES IN THE FIELD.

PMID- 18737478
TI  - UROLOGICAL PROBLEMS: THE CHAIRMAN'S ADDRESS.

PMID- 18737480
TI  - MONGOLISM.

PMID- 18737479
TI  - SURGICAL TREATMENT OF SEMINALVESICULITIS.

PMID- 18737482
TI  - BETTER TEACHING IN SCHOOLS OF NURSING.

PMID- 18737481
TI  - REPORT OF TWO CASES OF AMAUROTIC FAMILY IDIOCY (TAY-SACHS' DISEASE).

PMID- 18737483
TI  - SOCIAL INSURANCE.

PMID- 18737484
TI  - State Society.

PMID- 18737485
TI  - Society Reports.

PMID- 18737487
TI  - PUBLIC HEALTH NURSES.

PMID- 18737486
TI  - FROM A BELGIAN- SOLDIER.

PMID- 18737488
TI  - MEDICAL CERTIFICATE TO ESCAPE DRAFT.

PMID- 18737490
TI  - State Board of Health.

PMID- 18737489
TI  - OUR INDICTMENT OF GERMANY.

PMID- 18737492
TI  - AMERICAN MANUFACTURE OF SALVARSAN.

PMID- 18737491
TI  - State Board of Medical Examiners.

PMID- 18737493
TI  - CALIFORNIA DOCTORS IN SERVICE.

PMID- 18737494
TI  - APPENDICITIS IN CHILDHOOD-STUDY OF ONE HUNDRED CASES.

PMID- 18737495
TI  - RAT BITE FEVER WITH REPORT OF TWO CASES.

PMID- 18737497
TI  - A CLIPPED EDITORIAL.

PMID- 18737496
TI  - A CONSERVATIVE PHYSICIAN'S VIEW OF THE PROPOSED SOCIAL HEALTH INSURANCE SCHEMES.

PMID- 18737499
TI  - PERIODIC PHYSICAL EXAMINATION.

PMID- 18737498
TI  - THE CONSERVATION OF VITAMINS.

PMID- 18737500
TI  - EXFOLIATIVE CYSTITIS.

PMID- 18737501
TI  - INTERNAL HEMORRHOID OPERATION AND AFTER CARE UNDER QUININE-UREA HYDROCHLORIDE
      ANESTHESIA.

PMID- 18737502
TI  - SOME REMARKS ON LARYNGEAL AFFECTIONS.

PMID- 18737504
TI  - THE VENEREAL SILENCE.

PMID- 18737503
TI  - REPORT OF A CASE OF OTITIC MENINGITIS.

PMID- 18737505
TI  - EDITORIAL COMMENT.

PMID- 18737506
TI  - AN INTERESTING OPERATIVE EAR CASE.

PMID- 18737507
TI  - COLLOIDAL MASTIC REACTION OF CEREBROSPINAL FLUID.

PMID- 18737508
TI  - THE CARE OF THE FUNCTIONING BREAST.

PMID- 18737509
TI  - GASTROENTEROSTOMY: 100 CASES STUDIED POSTOPERATIVELY.

PMID- 18737511
TI  - PRESENT STATUS OF HEALTH INSURANCE IN CALIFORNIA.

PMID- 18737510
TI  - MINERAL SPRINGS AND SOME OF THEIR INTERNAL USES.

PMID- 18737512
TI  - REPORT OF A CASE OF CHARCOT JOINT OF THE SPINE.

PMID- 18737513
TI  - FOREIGN BODY LODGED IN LUNG AND REMOVED AFTER ELEVEN YEARS BY BRONCHOSCOPY.

PMID- 18737514
TI  - SPINAL CORD CHANGES IN COMBINED SCLEROSIS.

PMID- 18737516
TI  - PRAYER OF MAIMONIDES.

PMID- 18737515
TI  - THE VENEREAL SITUATION AMONG THE FORCES AT WAR.

PMID- 18737517
TI  - MEDICAL MILITARY EXPERIENCES.

PMID- 18737519
TI  - State Society.

PMID- 18737518
TI  - FROM ALLENTOWN.

PMID- 18737520
TI  - County Societies.

PMID- 18737521
TI  - A PRESSING QUESTION: SHALL WE USE OUR GRAIN FOR BREAD OR FOR BEER?

PMID- 18737523
TI  - FIRST SEMI-ANNUAL REPORT OF WAR COUNCIL OF THE AMERICAN RED CROSS.

PMID- 18737522
TI  - POPULAR MEDICAL LECTURES: STANFORD UNIVERSITY MEDICAL SCHOOL.

PMID- 18737525
TI  - Dr. John Taylor Jones.

PMID- 18737524
TI  - State Board of Medical Examiners: Annual Tax.

PMID- 18737526
TI  - State Society: Important Notice-Indemnity Defense Fund.

PMID- 18737527
TI  - County Societies.

PMID- 18737528
TI  - Correspondence.

PMID- 18737529
TI  - SAN FRANCISCO COLLEGE OF PHYSICIANS AND SURGEONS.

PMID- 18737530
TI  - ORTHOPEDIC DUTY IN ENGLAND.

PMID- 18737531
TI  - WEEDING OUT INCOMPETENT OFFICERS.

PMID- 18737532
TI  - NAVY CALLS FOR BINOCULARS.

PMID- 18737534
TI  - SCIENTIFIC PROGRAM.

PMID- 18737533
TI  - State Board of Medical Examiners: Excerpts from Opinions of Legal Department.

PMID- 18737535
TI  - RAILROAD RATES.

PMID- 18737536
TI  - INSURANCE AND THE INDEMNITY DEFENSE FUND.

PMID- 18737537
TI  - OBSESSIONS OF THE NORMAL MIND.

PMID- 18737538
TI  - THE CONTROL OF CANCER.

PMID- 18737539
TI  - EDITORIAL COMMENT.

PMID- 18737540
TI  - THE VASO-MOTOR SYMPTOMS OF THE MENOPAUSE.

PMID- 18737541
TI  - THE ARMY MEDICAL EXAMINATIONS OF THE FIRST DRAFT.

PMID- 18737542
TI  - TENTATIVE REPORT ON SOCIAL INSURANCE.

PMID- 18737543
TI  - TUBERCULOSIS OF THE EYE.

PMID- 18737544
TI  - COMPLEMENT FIXATION IN TUBERCULOSIS.

PMID- 18737545
TI  - THE DIFFERENTIATION OF SYPHILILITIC AND TUBERCULOUS PULMONARY LESIONS.

PMID- 18737547
TI  - PRACTICAL VALUE OF THE COMPLEMENT FIXATION TEST FOR GONORRHEA.

PMID- 18737546
TI  - METABOLISM AND DISEASE.

PMID- 18737548
TI  - COMMITTEE ON SCIENTIFIC PROGRAM.

PMID- 18737549
TI  - PATHOLOGIC EXHIBIT.

PMID- 18737550
TI  - DEL MONTE.

PMID- 18737551
TI  - UNSCIENTIFIC SCIENCE.

PMID- 18737552
TI  - GOOD ADVERTISING VALUE.

PMID- 18737553
TI  - ALARMS AND RUMORS.

PMID- 18737554
TI  - VENEREAL DISEASE AND THE ARMY.

PMID- 18737555
TI  - MEDICAL MOBILIZATION.

PMID- 18737557
TI  - WAR CLASSIFICATION OF MEDICAL COLLEGES.

PMID- 18737556
TI  - NAVY NEEDS MEDICAL OFFICERS.

PMID- 18737558
TI  - EDITORIAL COMMENT.

PMID- 18737559
TI  - THE WORK OF THE MEDICAL ADVISORY BOARD FOR DISTRICT EXEMPTION BOARD, DIVISION
      ONE, NORTHERN CALIFORNIA.

PMID- 18737560
TI  - VENEREAL DISEASE CONTROL BY BOARD OF HEALTH OF SAN FRANCISCO.

PMID- 18737561
TI  - NON-BEVERAGE ALCOHOL.

PMID- 18737562
TI  - HODGKIN'S DISEASE AND ITS TREATMENT, WITH A REPORT OF CASES.

PMID- 18737563
TI  - HEADACHE RESULTING FROM PATHOLOGICAL INTRA-ORAL AND INTRANASAL CONDITIONS.

PMID- 18737565
TI  - PYELOGRAMS OF TUMORS OF THE KIDNEYS.

PMID- 18737564
TI  - THE TREATMENT OF INFANTILE PARALYSIS.

PMID- 18737567
TI  - EXCERPTS FROM LETTERS OF DR. GEO. J. McCHESNEY TO DR. HARRY M. SHERMAN, SAN
      FRANCISCO.

PMID- 18737566
TI  - BOARD OF MEDICAL EXAMINERS.

PMID- 18737568
TI  - State Society.

PMID- 18737569
TI  - County Societies.

PMID- 18737570
TI  - Department of Pharmacy and Chemistry: Reporting of Accidents from Local
      Anesthetics.

PMID- 18737571
TI  - State Board of Pharmacy: Statutes Regulating Sale of Poisons.

PMID- 18737572
TI  - Rules for Government of Maternity Hospitals: State Board of Charities and
      Correction.

PMID- 18737574
TI  - VOLUNTEER MEDICAL SERVICE CORPS.

PMID- 18737573
TI  - DEL MONTE.

PMID- 18737576
TI  - MEASLES EPIDEMIC.

PMID- 18737575
TI  - PHYSICIANS' COMMISSIONS AND THE A. M. A.

PMID- 18737577
TI  - DEAD BABY OR DEAD GUINEA PIG.

PMID- 18737578
TI  - THE MENTAL HYGIENE MOVEMENT IN CALIFORNIA.

PMID- 18737579
TI  - DISTINCTION BETWEEN MEDICAL DEFENSE AND INDEMNITY DEFENSE FUND.

PMID- 18737580
TI  - EDITORIAL COMMENT.

PMID- 18737581
TI  - SPASMODIC VASO-MOTOR DISTURBANCES OF THE RESPIRATORY TRACT, WITH SPECIAL
      REFERENCE TO HAY FEVER: A PRELIMINARY REPORT.

PMID- 18737583
TI  - PERMANGANATE REDUCTION INDEX OF CEREBROSPINAL FLUID.

PMID- 18737582
TI  - THE COLLOIDAL GOLD (LANGE) TEST IN DIAGNOSIS. U. C. HOSPITAL.

PMID- 18737584
TI  - OBSTETRICAL ANESTHESIA.

PMID- 18737585
TI  - THE J. HENRY BARBAT PRIZE.

PMID- 18737586
TI  - REFRACTION IN CHILDREN.

PMID- 18737587
TI  - SOME OCULAR DEFECTS IN MENTALLY RETARDED CHILDREN.

PMID- 18737588
TI  - CONGENITAL OCCLUSION OF THE CHOANAE OF THE NOSE.

PMID- 18737589
TI  - KIDNEY INFECTIONS IN WOMEN.

PMID- 18737591
TI  - PRE-OPERATIVE INVESTIGATION BY GROUP STUDY SUGGESTED AS A METHOD FOR THE LOWERING
      OF SURGICAL FATALITIES.

PMID- 18737590
TI  - BACKWARD DISPLACEMENT OF THE UTERUS.

PMID- 18737592
TI  - CARDIOSPASM.

PMID- 18737593
TI  - A NEW DEVICE FOR HOLDING FRACTURES OF THE LONG BONES.

PMID- 18737594
TI  - VACCINE THERAPY.

PMID- 18737595
TI  - RECTAL HEMORRHAGE.

PMID- 18737596
TI  - THE MANAGEMENT OF SURGICAL RISK. A REVIEW OF 100 KIDNEY AND PROSTATE OPERATIONS,
      AND 50 CASES OF ENLARGED PROSTATE NOT OPERATED UPON.

PMID- 18737597
TI  - ACUTE GASTRO-DUODENAL PERFORATIONS: TREATMENTS, DIAGNOSIS, REPORTS OF SIX CASES,
      FOUR RECOVERIES.

PMID- 18737598
TI  - FROM SURGEON U. R. WEBB, U. S. N.

PMID- 18737599
TI  - CONCERNING AN EDITORIAL.

PMID- 18737601
TI  - From Dr. Sterling Bunnell, Secaucus, New Jersey.

PMID- 18737600
TI  - SOMEWHERE IN FRANCE, NEAR WHERE THE CANNONS CAN BE HEARD.

PMID- 18737602
TI  - SAN FRANCISCO POLYCLINIC WAR LETTERS: NOTES FROM CAMP LEWIS.

PMID- 18737604
TI  - From Dr. Bruce Ffoulkes, Camp Funston, Kansas.

PMID- 18737603
TI  - From Dr. Walter S. Johnson, Base Hospital, Camp Kearny.

PMID- 18737605
TI  - State Society.

PMID- 18737606
TI  - County Societies.

PMID- 18737607
TI  - CONTINUING NEED FOR SURGEONS IN MEDICAL RESERVE CORPS OF ARMY.

PMID- 18737608
TI  - REPORT OF PROVOST MARSHAL GENERAL ON FIRST DRAFT.

PMID- 18737609
TI  - THE DECLINING CIVILIZED BIRTH RATE.

PMID- 18737610
TI  - PHYSICIANS' REBATES FROM DEALERS.

PMID- 18737611
TI  - NURSES FOR THE NAVY.

PMID- 18737612
TI  - NEW PLANT FOODS FOR MAN.

PMID- 18737613
TI  - EDITORIAL COMMENT.

PMID- 18737614
TI  - MANUSCRIPTS FROM MEDICAL OFFICERS IN ARMY.

PMID- 18737615
TI  - REGULATION OF THE PRACTICE OF MEDICINE IN CALIFORNIA SINCE 1914.

PMID- 18737617
TI  - AMEBIASIS: ITS RADICAL CURE WITH COMBINED EMETIN AND SALVARSAN PRODUCTS.

PMID- 18737616
TI  - ARTHROPLASTY OF THE HIP JOINT, MURPHY METHOD, REPORT OF FOUR CASES.

PMID- 18737618
TI  - ACUTE GASTRO-DUODENAL PERFORATIONS.

PMID- 18737619
TI  - THE CONTROL OF EPIDEMIC MENINGITIS, WITH SOME OBSERVATIONS MADE DURING AN
      EPIDEMIC AT THE UNITED STATES NAVAL TRAINING STATION, SAN DIEGO, CALIFORNIA.

PMID- 18737620
TI  - THE TREATMENT OF WARTS.

PMID- 18737622
TI  - THE ETIOLOGY AND SYMPTOMATOLOGY OF CHRONIC SUPPURATIVE OTITIS.

PMID- 18737621
TI  - NITRO-BENZOL POISONING.

PMID- 18737623
TI  - THE PREVENTION AND TREATMENT OF LOCALIZED MUSCULAR CONTRACTURES.

PMID- 18737625
TI  - GONORRHOEA IN WOMEN.

PMID- 18737624
TI  - ARCH DEFECTS OF THE HUMAN FOOT.

PMID- 18737626
TI  - County Societies.

PMID- 18737627
TI  - PHYSICIAN WANTED.

PMID- 18737628
TI  - Department of Pharmacy and Chemistry.

PMID- 18737629
TI  - DECREASE IN BIRTH RATE IN HUNGARY.

PMID- 18737630
TI  - INTERNATIONAL SURGICAL SOCIETY.

PMID- 18737632
TI  - HOW TO OBTAIN COMMISSION.

PMID- 18737631
TI  - AN IMPERATIVE APPEAL FOR MEDICAL OFFICERS.

PMID- 18737633
TI  - MEDICAL EDUCATION IN TIME OF WAR.

PMID- 18737634
TI  - STAND BEHIND THE BOYS.

PMID- 18737636
TI  - REBATES FROM DRUGGISTS.

PMID- 18737635
TI  - THE SUPPRESSION OF QUACKS.

PMID- 18737637
TI  - SOCIAL INSURANCE.

PMID- 18737638
TI  - EDITORIAL COMMENT.

PMID- 18737639
TI  - TRAINING OF NURSES AND SOCIAL WORKERS IN THE PRESENT EMERGENCY.

PMID- 18737641
TI  - THE VALUE OF RENAL FUNCTIONAL STUDIES IN THE PROGNOSIS AND TREATMENT OF
      NEPHRITIS: WITH SPECIAL REFERENCE TO THE RENAL TEST DIET.

PMID- 18737640
TI  - THE INTERRELATIONSHIP OF ASTHMA AND TUBERCULOSIS.

PMID- 18737642
TI  - SCHISTOSOMIASIS IN CALIFORNIA.

PMID- 18737643
TI  - VENEREAL DISEASE CONTROL IN CALIFORNIA.

PMID- 18737644
TI  - LABORATORY TECHNIQUE CARRIED OUT IN STUDIES OF LOBAR PNEUMONIA IN BASE HOSPITAL
      LABORATORY, CAMP LEWIS, WASH., WITH REPORT OF SUBSTITUTION OF RABBITS FOR WHITE
      MICE, IN DETERMINATION OF PNEUMOCOCCUS TYPES.

PMID- 18737645
TI  - CEREBRAL OEDEMA IN INTRACRANIAL TRAUMA.

PMID- 18737646
TI  - SARCOMA OF THE CHOROID WITH REPORT OF TWO CASES.

PMID- 18737647
TI  - THE PASSAGE OF DRUGS FROM BLOOD SERUM TO THE SPINAL FLUID.

PMID- 18737648
TI  - EFFECT OF PNEUMATIC HAMMERS ON HEALTH.

PMID- 18737649
TI  - FROM DR. SHERMAN.

PMID- 18737650
TI  - State Society.

PMID- 18737651
TI  - County Societies.

PMID- 18737653
TI  - INFORMATION BUREAU ON NATION'S HOSPITALS.

PMID- 18737652
TI  - Pomona Valley Hospital.

PMID- 18737655
TI  - BUREAU OF VENEREAL DISEASES.

PMID- 18737654
TI  - Department of Pharmacy and Chemistry.

PMID- 18737656
TI  - National Children's Year Program: Adapted to California's Needs.

PMID- 18737658
TI  - IMPORTANCE OF RED CROSS HEALTH CERTIFICATES.

PMID- 18737657
TI  - THIS MEANS BUSINESS-READ IT!

PMID- 18737660
TI  - LEGAL ASPECTS OF SOCIAL INSURANCE.

PMID- 18737659
TI  - THE TREATMENT OF DRUG ADDICTION.

PMID- 18737662
TI  - EDITORIAL COMMENT.

PMID- 18737661
TI  - NUTRITION CLASSES.

PMID- 18737663
TI  - MEASUREMENTS OF AMERICAN SOLDIERS.

PMID- 18737664
TI  - METABOLISM IN DIABETES, NEPHRITIS AND CHOLECYSTITIS.

PMID- 18737665
TI  - AUTOGENOUS COLON VACCINES IN ECZEMA.

PMID- 18737666
TI  - GRANULOMA OF THE LARYNX.

PMID- 18737667
TI  - XANTHOMA TUBEROSUM MULTIPLEX.

PMID- 18737668
TI  - VINCENT'S ANGINA, WITH REPORT OF A CASE.

PMID- 18737670
TI  - ABSCESS OF LIVER IN YOUNG INFANT.

PMID- 18737669
TI  - NEUROLOGICAL ASPECT OF BRAIN TUMORS.

PMID- 18737671
TI  - THE CAUSE AND PREVENTION OF POST-OPERATIVE GAS PAINS.

PMID- 18737672
TI  - FROM DR. R. H. HUNT.

PMID- 18737673
TI  - MEDICAL WOMEN'S WAR SERVICE.

PMID- 18737674
TI  - County Societies.

PMID- 18737675
TI  - Head Measurements of Soldiers and Identification.

PMID- 18737676
TI  - American Women's Hospitals.

PMID- 18737678
TI  - VENEREAL DISEASE.

PMID- 18737677
TI  - THE PASSING OF THE DINOSAURS.

PMID- 18737679
TI  - COLOR BLINDNESS AMONG SEAMEN.

PMID- 18737680
TI  - NEW REGULATION FOR VENEREAL DISEASE REPORTS.

PMID- 18737682
TI  - UNIVERSAL SERVICE.

PMID- 18737681
TI  - TUBERCULOSIS SITUATION.

PMID- 18737683
TI  - EDITORIAL COMMENT.

PMID- 18737684
TI  - THE PREVENTION OF BLINDNESS WORK OF THE STATE INDUSTRIAL ACCIDENT COMMISSION.

PMID- 18737685
TI  - A PLEA FOR A COMPLETE UROLOGICAL DIAGNOSIS AT ONE SITTING: PRELIMINARY
      COMMUNICATION.

PMID- 18737687
TI  - RESULTS FOLLOWING OPERATIVE TREATMENT OF PELVIC INFLAMMATORY DISEASE IN THE
      STANFORD UNIVERSITY CLINIC.

PMID- 18737686
TI  - THE PREVENTION OF CONGENITAL SYPHILIS BY ANTILUETIC PRENATAL THERAPY.

PMID- 18737688
TI  - TRAINING OF FIXATION AND FUSION IN STRABISMUS.

PMID- 18737690
TI  - County Societies.

PMID- 18737689
TI  - DOCTORS WANTED FOR RED CROSS: BUREAU OF MEDICAL SERVICE.

PMID- 18737691
TI  - Address of President Wilson, July 4, 1918, Mount Vernon.

PMID- 18737692
TI  - GUARDING CAMPS FROM FLIES AND MOSQUITOES.

PMID- 18737694
TI  - Department of Pharmacy and Chemistry.

PMID- 18737693
TI  - CARE IN REPORTING DISEASES THAT MIGHT MENACE HEALTH OF TROOPS URGED UPON DOCTORS.

PMID- 18737695
TI  - IN ERRATA.

PMID- 18737696
TI  - State Board of Medical Examiners.

PMID- 18737697
TI  - A WAR MESSAGE FROM PRESIDENT VAN ZWALENBURG.

PMID- 18737698
TI  - CARE OF THE CHILD.

PMID- 18737699
TI  - THE CHILDREN'S YEAR IN CALIFORNIA.

PMID- 18737700
TI  - RED CHEVRON.

PMID- 18737702
TI  - EYE HAZARDS.

PMID- 18737701
TI  - THE NEW CRIMINOLOGY.

PMID- 18737703
TI  - FOR ARMY PHARMACEUTICAL CORPS.

PMID- 18737704
TI  - EDITORIAL COMMENT.

PMID- 18737705
TI  - THE CHILDREN'S YEAR-AN OPPORTUNITY IN PREVENTIVE MEDICINE.

PMID- 18737707
TI  - SOCIAL PROBLEMS OF THE WAR.

PMID- 18737706
TI  - PLASTIC SURGERY OF NOSE AND EARS: A FURTHER CONTRIBUTION.

PMID- 18737708
TI  - AN ANALYSIS OF THE FIRST TWO HUNDRED CASES STUDIED AT THE SAN DIEGO DIAGNOSTIC
      GROUP CLINIC.

PMID- 18737709
TI  - INTESTINAL OBSTRUCTION.

PMID- 18737710
TI  - CLINICAL ASPECTS OF THE FASTING TREATMENT OF DIABETES.

PMID- 18737711
TI  - FROM PRESIDENT BEVAN OF A. M. A.

PMID- 18737712
TI  - Stanford-Polyclinic Colloquia.

PMID- 18737713
TI  - State Society: Attitude of Gubernatorial Candidates on Social Health Insurance.

PMID- 18737714
TI  - California League for the Conservation of Public Health.

PMID- 18737715
TI  - County Societies.

PMID- 18737716
TI  - State Board of Medical Examiners: Optometry.

PMID- 18737717
TI  - FOURTH LIBERTY LOAN.

PMID- 18737719
TI  - VOLUNTEER MEDICAL SERVICE CORPS.

PMID- 18737718
TI  - THE DENTAL INITIATIVE.

PMID- 18737720
TI  - FIFTY THOUSAND MEDICAL OFFICERS.

PMID- 18737721
TI  - IMPORTANT CHANGE IN U. S. EMPLOYMENT CONDITIONS.

PMID- 18737723
TI  - A NON-ESSENTIAL INDUSTRY.

PMID- 18737722
TI  - DEMOCRACY VS. TIPS.

PMID- 18737724
TI  - URGENT NEED FOR NURSES.

PMID- 18737725
TI  - THE HEALTH OFFICER AND THE WAR.

PMID- 18737726
TI  - EDITORIAL COMMENT.

PMID- 18737728
TI  - DR. JOHN GALLWEY'S ARGUMENT AGAINST COMPULSORY HEALTH INSURANCE.

PMID- 18737727
TI  - THE DENTAL INITIATIVE.

PMID- 18737729
TI  - CEREBROSPINAL FLUID FINDINGS IN HERPES ZOSTER.

PMID- 18737730
TI  - IS PURGATION JUSTIFIABLE?

PMID- 18737731
TI  - PUBIOTOMY.

PMID- 18737732
TI  - A CONTRIBUTION ON FOCAL RENAL INFECTIONS.

PMID- 18737733
TI  - THE PREVALENCE OF STREPTOCOCCAL INFECTIONS.

PMID- 18737734
TI  - INTESTINAL OBSTRUCTION: WITH REPORT OF A CASE OCCURRING IN A GEOPHAGIST.

PMID- 18737735
TI  - A METHOD OF SUTURING "Y" SHAPED WOUNDS.

PMID- 18737736
TI  - A PLEA FOR BETTER CO-OPERATION BETWEEN PHYSICIANS AND DENTISTS.

PMID- 18737737
TI  - Concerning Physicians and Surgeons College, San Francisco.

PMID- 18737738
TI  - FROM DR. R. H. HUNT, "OVER THERE" WITH THE NAVY.

PMID- 18737739
TI  - County Societies.

PMID- 18737740
TI  - Social Insurance.

PMID- 18737741
TI  - State Board of Health.

PMID- 18737742
TI  - Department of Pharmacy and Chemistry.

PMID- 18737743
TI  - INFLUENZA.

PMID- 18737745
TI  - THE PSYCHOPATHIC HOSPITAL IDEA.

PMID- 18737744
TI  - VOLUNTEER MEDICAL SERVICE CORPS.

PMID- 18737747
TI  - EDITORIAL COMMENT.

PMID- 18737746
TI  - THE COMMUNAL KITCHEN.

PMID- 18737749
TI  - SYPHILIS OF THE THYROID GLAND REPORT OF A CASE.

PMID- 18737748
TI  - FLIGHT SURGEONS.

PMID- 18737750
TI  - SEMINAL VESICULOTOMY IN THE TREATMENT OF GONORRHEAL RHEUMATISM.

PMID- 18737752
TI  - TREATMENT OF SYPHILIS OF THE CENTRAL NERVOUS SYSTEM.

PMID- 18737751
TI  - DISEASE OF THE AORTA AS SHOWN BY FLUOROSCOPIC STUDY.

PMID- 18737753
TI  - CONSERVATION OF CHILDREN.

PMID- 18737754
TI  - DIVERTICULA OF THE FEMALE URETHRA.

PMID- 18737755
TI  - RADIUM IN THE TREATMENT OF UTERINE CANCER WITH CASE REPORTS.

PMID- 18737757
TI  - A STUDY OF THE LUNG REFLEXES IN PULMONARY TUBERCULOSIS.

PMID- 18737756
TI  - THE X-RAY TREATMENT OF UTERINE FIBROIDS.

PMID- 18737758
TI  - Special Department: No Covenanted Peace with Germany.

PMID- 18737760
TI  - County Societies.

PMID- 18737759
TI  - AN UNPRECEDENTED OPPORTUNITY FOR WOMEN.

PMID- 18737762
TI  - LICENSE EXAMINATIONS IN FOREIGN LANGUAGE.

PMID- 18737761
TI  - Correspondence.

PMID- 18737763
TI  - Correspondence.

PMID- 18737765
TI  - FOR ARMY NURSES AT BASE HOSPITALS.

PMID- 18737764
TI  - Correspondence.

PMID- 18737767
TI  - FEAR AND EPIDEMICS.

PMID- 18737766
TI  - SHELL SHOCK.

PMID- 18737768
TI  - DEPARTMENT OF INDUSTRIAL MEDICINE.

PMID- 18737769
TI  - RED CROSS HOSPITAL WORK IN FRANCE.

PMID- 18737770
TI  - EDITORIAL COMMENT.

PMID- 18737771
TI  - BIRTH REGISTRATION IN CALIFORNIA: A PART OF THE CHILDREN'S YEAR PROGRAM.

PMID- 18737772
TI  - INTRACRANIAL COMPLICATIONS OF DISEASES OF THE EAR, NOSE AND THROAT.-A REPORT OF
      SOME UNUSUAL CASES WITH AUTOPSY FINDINGS.

PMID- 18737773
TI  - DISPENSARY TREATMENT OF DIABETICS.

PMID- 18737774
TI  - CLINICAL RESULTS FOLLOWING PROPHYLACTIC TREATMENT WITH SILVER NITRATE FOR
      BLENORRHEA NEONATORUM.

PMID- 18737775
TI  - ACUTE AND SUBACUTE UNILATERAL INFECTIOUS NEPHRITIS WITHOUT PYURIA FROM THE
      AFFECTED SIDE.

PMID- 18737777
TI  - INFLUENZA PREVENTION.

PMID- 18737776
TI  - RESULTS FROM PERTUSSIS VACCINE.

PMID- 18737778
TI  - Concerning Anesthetists.

PMID- 18737779
TI  - Correspondence.

PMID- 18737780
TI  - County Societies.

PMID- 18737781
TI  - State Board of Medical Examiners.

PMID- 18737782
TI  - Correspondence.

PMID- 18737783
TI  - State Society.

PMID- 18737784
TI  - REDUCING INDUSTRIAL FATIGUE.

PMID- 18737785
TI  - Santa Barbara 1919.

PMID- 18737786
TI  - The Karrell Cure Revived.

PMID- 18737788
TI  - OF FADS AND SPECIALISMS.

PMID- 18737787
TI  - Pitfalls in the Diagnosis and Treatment of Senile Hypertrophy of the Prostate.

PMID- 18737789
TI  - Abdominal Cesarian Section. Indications and Technique.

PMID- 18737791
TI  - San Francisco Hospital Colloquia.

PMID- 18737790
TI  - Drugs in Their Local Application to Ear, Nose and Throat Treatment.

PMID- 18737792
TI  - INTERESTING COMMENTS FROM PARIS.

PMID- 18737793
TI  - SCHOOL ATHLETICS.

PMID- 18737795
TI  - County Societies.

PMID- 18737794
TI  - Editorial Comment.

PMID- 18737796
TI  - Department of Industrial Medicine.

PMID- 18737797
TI  - Department of Pharmacy and Chemistry.

PMID- 18737798
TI  - Grip of Germany on Many Industries.

PMID- 18737799
TI  - The Treatment of Laboratory Control of Diabetes.

PMID- 18737800
TI  - NOTICE PARTICULARLY.

PMID- 18737802
TI  - INFLUENZA CONTROL.

PMID- 18737801
TI  - STATE PROGRAM BEING FILLED.

PMID- 18737803
TI  - FAT EMBOLISM AND SHOCK.

PMID- 18737804
TI  - A DEBT TO HEROES.

PMID- 18737805
TI  - THE SAN FRANCISCO BULLETIN.

PMID- 18737806
TI  - THE PHYSICIAN AND THE INDUSTRIAL ACCIDENT COMMISSION.

PMID- 18737807
TI  - SURE CURE FOR INFLUENZA.

PMID- 18737808
TI  - DRUGGISTS AND THE VENEREAL CAMPAIGN.

PMID- 18737809
TI  - EDITORIAL COMMENT.

PMID- 18737810
TI  - COMMUNICATION ON POST-INFLUENZAL EMPYEMA AND LUNG ABSCESS.

PMID- 18737811
TI  - CHILD HYGIENE BUREAU.

PMID- 18737812
TI  - PATHOLOGY AND TREATMENT OF INFLUENZAL PNEUMONIA.

PMID- 18737813
TI  - RATTLESNAKES: THEIR VENOM AND ANTIDOTES.

PMID- 18737814
TI  - TUBERCULOSIS OF THE UTERUS.

PMID- 18737815
TI  - DIAGNOSIS AND TREATMENT OF GLANDULAR OBSTRUCTION AT THE NECK OF BLADDER.

PMID- 18737816
TI  - RECURRENCE OF STONE IN THE KIDNEY AFTER OPERATION.

PMID- 18737818
TI  - County Societies.

PMID- 18737817
TI  - PHYSICIANS IN INDUSTRIAL PRACTICE.

PMID- 18737819
TI  - DISPOSAL OF EXCRETA ON RAILROADS.

PMID- 18737820
TI  - THE PHYSICIAN AFTER THE WAR.

PMID- 18737821
TI  - THE ONLY HOPELESS CRIPPLE.

PMID- 18737822
TI  - Harrison Law.

PMID- 18737823
TI  - Vivisection Debate at the Commonwealth Club.

PMID- 18737825
TI  - HEALTH DAY.

PMID- 18737824
TI  - The Red Cross and the Disabled Soldier or Sailor.

PMID- 18737827
TI  - IMMUNITY.

PMID- 18737826
TI  - VICIOUS LEGISLATION.

PMID- 18737828
TI  - SCRIPTO-DICTO PARALYSIS MEDICORUM?

PMID- 18737829
TI  - STATE PSYCHOPATHIC HOSPITAL.

PMID- 18737830
TI  - EDITORIAL COMMENT.

PMID- 18737831
TI  - THE LOS ANGELES COUNTY HOSPITAL.

PMID- 18737832
TI  - BUREAU OF CHILD HYGIENE.

PMID- 18737834
TI  - ELECTRICITY APPLIED IN GYNECOLOGY.

PMID- 18737833
TI  - A STUDY OF ACHYLIA GASTRICA BY THE FRACTIONAL METHOD.

PMID- 18737835
TI  - HEREDITARY HEMORRHAGIC TELANGIECTASES.

PMID- 18737837
TI  - Los Angeles County Hospital.

PMID- 18737836
TI  - SOME INTERESTING SURGICAL CONDITIONS OF THE KIDNEY AND PROSTATE.

PMID- 18737838
TI  - TUBERCULOSIS AFTER INFLUENZA.

PMID- 18737839
TI  - LICENSURE OF PHYSICIANS FROM MILITARY SERVICE.

PMID- 18737840
TI  - WORKMEN'S COMPENSATION RED TAPE.

PMID- 18737841
TI  - WHAT'S THE ANSWER?

PMID- 18737842
TI  - State Society.

PMID- 18737843
TI  - County Societies.

PMID- 18737844
TI  - CONSTITUTION OF THE MEDICAL SOCIETY OF THE STATE OF CALIFORNIA.

PMID- 18737845
TI  - CONSTITUTION OF THE MEDICAL SOCIETY OF THE STATE OF CALIFORNIA.

PMID- 18737846
TI  - Milk for Children.

PMID- 18737847
TI  - Department of Pharmacy and Chemistry.

PMID- 18737848
TI  - Red Cross Relief in Palestine.

PMID- 18737849
TI  - SPLENDID PROGRAM.

PMID- 18737850
TI  - MORE REMARKS ON THE PROGRAM OF THE APRIL MEETING.

PMID- 18737851
TI  - WHEN DOCTORS DISAGREE.

PMID- 18737852
TI  - PAYMENT OF STATE TAX.

PMID- 18737854
TI  - THE BUSINESS OF MEDICINE.

PMID- 18737853
TI  - PUBLIC HEALTH AND STREET RAILWAYS.

PMID- 18737856
TI  - VOLUNTEER MEDICAL SERVICE CORPS QUESTIONNAIRES.

PMID- 18737855
TI  - THE SMALL TOWN HOSPITAL.

PMID- 18737857
TI  - EDITORIAL COMMENT.

PMID- 18737859
TI  - REPORT OF A CASE OF RUPTURED UTERUS THROUGH A CAESARIN SCAR.

PMID- 18737858
TI  - ENDOCRINE GLANDS AND THEIR RELATION TO VASO MOTOR DISTURBANCES OF THE AIR
      PASSAGES, HAY FEVER AND ASTHMA, WITH THE PAST YEAR'S REPORT.

PMID- 18737860
TI  - THE CLASSIFICATION OF NAVAL RECRUITS.

PMID- 18737861
TI  - A SANE YET NON-SAFE FOURTH.

PMID- 18737862
TI  - ASSEMBLY BILL NO. 798.

PMID- 18737863
TI  - ADVICE FROM A COLLECTOR.

PMID- 18737864
TI  - MEDICAL EXAMINERS' ASSOCIATION.

PMID- 18737865
TI  - AGAINST MONOPOLISTIC STATE ACCIDENT INSURANCE.

PMID- 18737867
TI  - A JUST COMPLAINT FROM A WOMAN PHYSICIAN.

PMID- 18737866
TI  - AN ODOROUS SITUATION.

PMID- 18737868
TI  - State Society.

PMID- 18737869
TI  - County Societies.

PMID- 18737871
TI  - Department of Pharmacy and Chemistry.

PMID- 18737870
TI  - COUNTY MEDICAL MEETINGS.

PMID- 18737872
TI  - State Board of Health: Uses of Birth Certificates.

PMID- 18737873
TI  - Industrial Medicine: Labor Maxims.

PMID- 18737874
TI  - WAR INFLUENCE UPON EDUCATION.

PMID- 18737875
TI  - TELL HIM HE HAS A JOB.

PMID- 18737876
TI  - California Poor Relief System.

PMID- 18737877
TI  - Dr. Farrand Appointed Head of Red Cross.

PMID- 18737878
TI  - FROM THE RETIRING PRESIDENT.

PMID- 18737879
TI  - LEAGUE LUNCHEON.

PMID- 18737880
TI  - HOSPITAL IMPROVEMENT AND STANDARDIZATION.

PMID- 18737881
TI  - WAR LESSONS IN PUBLIC HEALTH.

PMID- 18737882
TI  - WOMEN IN INDUSTRY.

PMID- 18737883
TI  - VOLUNTEER MEDICAL SERVICE CORPS.

PMID- 18737884
TI  - DIPHTHERIA CONTROL.

PMID- 18737885
TI  - EDITORIAL COMMENT.

PMID- 18737886
TI  - LETHARGIC ENCEPHALITIS.

PMID- 18737887
TI  - RED CROSS WELFARE WORK IN PARIS, FRANCE.

PMID- 18737889
TI  - TUBERCULOSIS A GOVERNMENT PROBLEM.

PMID- 18737888
TI  - ENDOCRINE GLANDS AND THEIR RELATION TO VASO MOTOR DISTURBANCES OF THE AIR
      PASSAGES, HAY FEVER AND ASTHMA, WITH THE PAST YEAR'S REPORT.

PMID- 18737891
TI  - LOS ANGELES SIGN-POSTS.

PMID- 18737890
TI  - THE INFLUENZA EPIDEMIC IN STUDENTS' ARMY TRAINING CAMP, LOS ANGELES.

PMID- 18737893
TI  - AGREES WITH WOMAN PHYSICIAN.

PMID- 18737892
TI  - DISAGREES WITH WOMAN PHYSICIAN.

PMID- 18737894
TI  - NEVADA INVITATION.

PMID- 18737896
TI  - CONCERNING AN IMMUNITY LETTER.

PMID- 18737895
TI  - CRITICISM OF EDITORIAL.

PMID- 18737898
TI  - County Societies.

PMID- 18737897
TI  - PUBLICATION OF PAPERS BY ARMY MEDICAL OFFICERS.

PMID- 18737900
TI  - THE WILLOWS SANITARIUM.

PMID- 18737899
TI  - State Society.

PMID- 18737901
TI  - Department of Pharmacy and Chemistry.

PMID- 18737902
TI  - FOR DOCTORS IN SMALLER TOWNS.

PMID- 18737903
TI  - CORRECTION OF ABUSES UNDER THE WORKMEN'S COMPENSATION ACT.

PMID- 18737904
TI  - THE PSEUDO-MEDICAL PARASITE.

PMID- 18737905
TI  - PHYSICIAN HEADS SOCIAL AGENCIES.

PMID- 18737907
TI  - TRANSLATING MEDICAL KNOWLEDGE FOR POPULAR USE.

PMID- 18737906
TI  - PUBLIC HEALTH AND HIGH COST OF LIVING.

PMID- 18737908
TI  - SMALLPOX INCREASING IN CALIFORNIA.

PMID- 18737909
TI  - SOME OBSERVATIONS NOTED IN THE WORK OF THE MEDICAL ADVISORY BOARD OF THE HEALTH
      COMMISSION.

PMID- 18737910
TI  - ABSORPTION WITHOUT NEEDLING OF CATARACTOUS LENS, DUE TO PUNCTURED WOUND.

PMID- 18737911
TI  - LOCALIZATION OF FOREIGN BODIES IN THE EYE.

PMID- 18737912
TI  - NAVY BASE HOSPITAL NO. 3.

PMID- 18737913
TI  - REVIEW OF FIVE HUNDRED OPERATIONS FOR BATTLE CASUALTIES.

PMID- 18737914
TI  - SPINAL ANESTHESIA IN UPPER ABDOMINAL SURGERY.

PMID- 18737915
TI  - A JUDICIOUS CRITIC.

PMID- 18737917
TI  - RE ANNUAL TAX-GOVERNMENT SERVICE.

PMID- 18737916
TI  - DEFECTS IN CALIFORNIA'S INDUSTRIAL ACCIDENT INSURANCE LAW.

PMID- 18737918
TI  - County Societies.

PMID- 18737919
TI  - League for Conservation of Public Health: Luncheon at Hotel Belvedere, Santa
      Barbara, April 16, 1919.

PMID- 18737920
TI  - Los Angeles County Influenza Recommendations.

PMID- 18737922
TI  - Memorial Laboratory Dedication.

PMID- 18737921
TI  - Department of Pharmacy and Chemistry.

PMID- 18737924
TI  - HOSPITAL EFFICIENCY.

PMID- 18737923
TI  - RELATION OF THE HOSPITAL TO THE PATIENT.

PMID- 18737925
TI  - HEALTH LEAGUE OF NATIONS.

PMID- 18737926
TI  - EDITORIAL COMMENT.

PMID- 18737928
TI  - LEAGUE ENDORSEMENT.

PMID- 18737927
TI  - FITTING FEET WITH FAULTLESS FOOTGEAR.

PMID- 18737929
TI  - THE ROLL CALL AND RESULTS.

PMID- 18737930
TI  - A REVIEW OF OUR KNOWLEDGE CONCERNING THE ETIOLOGY OF INFLUENZA.

PMID- 18737931
TI  - A REPORT OF INFLUENZA PNEUMONIA.

PMID- 18737932
TI  - A CONSIDERATION OF THE METHODS USED IN THE CONTROL OF INFLUENZA.

PMID- 18737933
TI  - SOME CLINICAL FEATURES OF THE PRESENT PANDEMIC OF INFLUENZA AS COMPARED WITH THE
      PANDEMIC OF THIRTY YEARS AGO.

PMID- 18737934
TI  - THE TREATMENT OF POST-INFLUENZAL PNEUMONIA IN AN ARMY HOSPITAL.

PMID- 18737935
TI  - PULMONARY CONDITIONS WRONGLY DIAGNOSED AS TUBERCULOSIS.

PMID- 18737936
TI  - A REVIEW OF THE PNEUMONIA OF LAST YEAR.

PMID- 18737937
TI  - CYSTITIS AS A DIAGNOSTIC FALLACY.

PMID- 18737939
TI  - STOP THE JOURNAL.

PMID- 18737938
TI  - COMPLETE INVERSION OF THE UTERUS.

PMID- 18737940
TI  - County Societies.

PMID- 18737941
TI  - REFERRED TO THE "BORED" MEDICAL EXAMINERS.

PMID- 18737942
TI  - Red Cross Snap Shots.

PMID- 18737943
TI  - Department of Pharmacy and Chemistry.

PMID- 18737944
TI  - VOCATIONAL STUDY OF TUBERCULOSIS.

PMID- 18737945
TI  - LEAGUE RALLY AT SAN DIEGO, SEPTEMBER 9.

PMID- 18737946
TI  - TO OUR DOCTORS.

PMID- 18737948
TI  - THE INDEMNITY DEFENSE FUND.

PMID- 18737947
TI  - THE LEGAL DEPARTMENT.

PMID- 18737949
TI  - ADDITION TO EDITORIAL STAFF OF JOURNAL.

PMID- 18737950
TI  - PRIVATE ENTERPRISE AND PUBLIC HEALTH PROMOTION.

PMID- 18737951
TI  - CONCERNING REPRINTS AND OUR PUBLISHERS.

PMID- 18737952
TI  - SPLITTING INSURANCE FEES.

PMID- 18737953
TI  - Editorial Comment.

PMID- 18737954
TI  - Presidential Address.

PMID- 18737955
TI  - PROSTITUTION IN ITS RELATION TO PUBLIC HEALTH IN SAN FRANCISCO.

PMID- 18737957
TI  - A PRELIMINARY REPORT UPON THE TREATMENT OF HAY FEVER BY ALCOHOLIC INJECTION.

PMID- 18737956
TI  - THE PHYSICIAN AND INDUSTRY.

PMID- 18737958
TI  - CHILDREN'S YEAR IN CALIFORNIA.

PMID- 18737959
TI  - UNSATISFACTORY RESULTS FOLLOWING NON-INFECTED FINGER INJURIES IN INDUSTRIAL
      ACCIDENTS WITH SPECIAL REFERENCE TO AMPUTATIONS.

PMID- 18737960
TI  - THE PROBLEM OF THE WOMAN VENEREAL DISEASE CARRIER.

PMID- 18737962
TI  - THE OBSTETRICAL SITUATION IN FRANCE TODAY.

PMID- 18737961
TI  - THE TREATMENT OF GONORRHEA AND SYPHILIS IN WOMEN.

PMID- 18737963
TI  - PERFORATION IN GASTRIC AND DUODENAL ULCERS. CASE REPORTS.

PMID- 18737964
TI  - TREATMENT OF THE DIPHTHERIA CARRIER, WITH SPECIAL REFERENCE TO TONSILLECTOMY AND
      ADENOIDECTOMY: WITH REPORT OF 12 CASES.

PMID- 18737965
TI  - THE USE OF HOMATROPIN IN REFRACTION.

PMID- 18737966
TI  - INJUSTICE TO A STATE SOCIETY MEMBER.

PMID- 18737967
TI  - From Our A. M. A. Delegates: Personal Impressions of the A. M. A. Meeting.

PMID- 18737968
TI  - THE LAMP OF SCIENCE.

PMID- 18737969
TI  - FROM DR. V. G. VECKI.

PMID- 18737970
TI  - STRAIGHT FROM THE SHOULDER.

PMID- 18737972
TI  - PUTS R. A. C. ON THE RACK.

PMID- 18737971
TI  - EXCERPT FROM A HOT ONE.

PMID- 18737974
TI  - County Societies.

PMID- 18737973
TI  - INTERESTING, IF TRUE.

PMID- 18737975
TI  - State Board of Medical Examiners.

PMID- 18737976
TI  - Department of Pharmacy and Chemistry.

PMID- 18737977
TI  - MEDICAL USES OF WINES AND SPIRITS: TREASURY DEPARTMENT.

PMID- 18737979
TI  - Important! Please Read.

PMID- 18737978
TI  - California State Civil Service Examinations: Assistant Physician and Interne
      State Hospitals for the Insane.

PMID- 18737980
TI  - Why Report Venereal Disease?

PMID- 18737981
TI  - Proposed Plan for World-Wide Co-ordination of Red Cross Activities.

PMID- 18737983
TI  - LOCATIONS FOR DOCTORS.

PMID- 18737982
TI  - LINES OF EFFECTIVE PREVENTIVE MEDICINE.

PMID- 18737984
TI  - THE BOY SCOUTS' OATH.

PMID- 18737985
TI  - SYPHILIS MUST GO.

PMID- 18737986
TI  - NEW YORK PHYSICIANS TO FORM UNION.

PMID- 18737987
TI  - MEDICAL EXAMINATIONS.

PMID- 18737988
TI  - VACATION AND SOME EXPERTS.

PMID- 18737989
TI  - TECHNIC FOR THE REMOVAL OF DEAD TEETH.

PMID- 18737990
TI  - EDITORIAL COMMENT.

PMID- 18737991
TI  - THE SPECIALTY OF OBSTETRICS; ITS PRESENT STATUS; ITS POSSIBILITIES AND ITS
      IMPORTANCE.

PMID- 18737992
TI  - PREGNANCY AFTER UTERINE SUSPENSION.

PMID- 18737993
TI  - INFECTIONS OF THE ORAL CAVITY AND THEIR RELATIONS TO SYSTEMIC DISEASES.

PMID- 18737995
TI  - INCREASED SPINAL FLUID PRESSURE AS AN INDICATOR OF MENINGEAL DISEASE.

PMID- 18737994
TI  - THE EPIDEMIC OF FILARIA-ONCHOCERCA.

PMID- 18737996
TI  - THE RAPID ADMINISTRATION OF DIGITALIS IN CARDIAC DECOMPENSATION.

PMID- 18737997
TI  - NEPHROLITHIASIS: REPORT OF A RATHER UNUSUAL CASE.

PMID- 18737998
TI  - A SCHEMATIC METHOD FOR ESTIMATING THE HEALTH STATUS OF THE RUNABOUT CHILD.

PMID- 18737999
TI  - ECONOMICAL ASPECTS OF STATE HOSPITAL DISCHARGES AND PAROLES.

PMID- 18738000
TI  - THE USE OF CAMPHOR AS A STIMULANT AND AS A PNEUMOCOCCICIDE IN PNEUMONIA.

PMID- 18738001
TI  - FOCAL INFECTIONS AND NERVE REFLEXES AS RELATED TO THE EYE.

PMID- 18738002
TI  - WILL THE WAR INFLUENCE THE PRACTICE OF MEDICINE, AS A BUSINESS.

PMID- 18738005
TI  - County Societies.

PMID- 18738006
TI  - Public Health Service in San Diego.

PMID- 18738007
TI  - ELECT MEMBERS OF THE INDEMNITY DEFENSE FUND.

PMID- 18738008
TI  - HEALTH INSURANCE.

PMID- 18738009
TI  - FOR MEN RETURNING FROM SERVICE.

PMID- 18738010
TI  - MEXICAN HAIRLESS.

PMID- 18738012
TI  - PRESIDENT OF CALIFORNIA OSTEOPATHIC ASSOCIATION MAKES SERIOUS CHARGES-PROOFS
      DEMANDED.

PMID- 18738011
TI  - JUSTICE TO DR. RICHARDSON.

PMID- 18738013
TI  - CONSTRUCTIVE SUGGESTIONS WANTED ON MEDICAL PRACTICE ACT.

PMID- 18738014
TI  - WHAT IS MEDICINE?

PMID- 18738015
TI  - SCHOOLS ARE PUBLIC NOT THE CHILDREN.

PMID- 18738016
TI  - THE CALIFORNIA PROBLEM OF CRIPPLED CHILDREN.

PMID- 18738017
TI  - ANOTHER APPEAL TO CUPIDITY.

PMID- 18738019
TI  - MAKING SCIENCE POPULAR.

PMID- 18738018
TI  - ARE THERE ENOUGH DOCTORS?

PMID- 18738020
TI  - Editorial Comment.

PMID- 18738021
TI  - THE NEED FOR A STATE HOSPITAL SCHOOL FOR INDIGENT CRIPPLED AND DEFORMED CHILDREN.

PMID- 18738022
TI  - DEATH FROM ACCIDENTAL POISONING BY CARBOLIC ACID.

PMID- 18738023
TI  - THE SURPRISING FREQUENCY OF HYPERTENSION IN A GROUP OF YOUNG DRAFTED MEN.

PMID- 18738024
TI  - AMINO ACIDS AND HYPERTENSION.

PMID- 18738025
TI  - A STUDY OF ONE HUNDRED AND FIFTY CASES OF HYPERTENSION.

PMID- 18738026
TI  - PARALYSIS OF THE ESOPHAGUS.

PMID- 18738027
TI  - REPORT OF A CASE OF THE OPERATION OF BOTTINI FOR PROSTATIC OBSTRUCTION, AFTER
      TWENTY YEARS, and REPORT OF A CASE OF THE OPERATION OF GARRITY FOR CANCER OF THE
      PROSTATE, AFTER SIX MONTHS.

PMID- 18738028
TI  - THE INTENSIVE TREATMENT OF MENINGOCOCCIC MENINGITIS.

PMID- 18738029
TI  - EMPYEMA-TREATED BY DAKIN'S SOLUTION.

PMID- 18738031
TI  - San Francisco Shows Lowest Infant Mortality: San Francisco Department of Health.

PMID- 18738030
TI  - THE PATHOGENESIS OF PACHYMENINGITIS DUE TO NASAL OPERATIONS, WITH REPORT OF
      CASES.

PMID- 18738032
TI  - DR. VAN ZWALENBURG AT A. M. A.

PMID- 18738034
TI  - A MAN OF RARE JUDGMENT.

PMID- 18738033
TI  - PREVENTIVE DENTISTRY INVITATION.

PMID- 18738036
TI  - State Society.

PMID- 18738035
TI  - County Societies.

PMID- 18738037
TI  - LOS ANGELES AND SAN FRANCISCO PHYSICIANS SKIP THIS.

PMID- 18738038
TI  - WANTED!: AN ABLE-BODIED KICKER, CAPABLE OF RUNNING ONE PERFECTLY GOOD MEDICAL
      SOCIETY.

PMID- 18738039
TI  - THE IDEAL DOCTOR.

PMID- 18738040
TI  - PROTECT THE FLIES AND SWAT THE DOCTORS.

PMID- 18738041
TI  - HEALTH HECKLERS.

PMID- 18738042
TI  - SIR WILLIAM OSLER'S CORRESPONDENCE.

PMID- 18738043
TI  - ANOTHER FAKER AT LARGE.

PMID- 18738045
TI  - EDITORIAL COMMENT.

PMID- 18738044
TI  - THIRD SURVEY OF HOSPITALS.

PMID- 18738046
TI  - PLASTER METHODS OF TREATING MUSCLE CONTRACTURES FOLLOWING WOUNDS.

PMID- 18738047
TI  - CASE OF LEPTO-MENINGITIS OF OTITIC ORIGIN.

PMID- 18738048
TI  - THE POSSIBLE RELATIONSHIP OF DENTAL ABSCESSES AND THE TOXEMIAS OF PREGNANCY.

PMID- 18738049
TI  - PATHOLOGIC INDICATIONS FOR CHOLECYSTECTOMY.

PMID- 18738050
TI  - ACRIFLAVINE: A NEW GONOCOCCICIDE.

PMID- 18738051
TI  - THE OBSTETRICAL SOCIETY OF SAN FRANCISCO: A REMINISCENCE.

PMID- 18738052
TI  - ABDOMINAL WAR WOUNDS.

PMID- 18738053
TI  - MEDICAL PRACTICE ACT SUGGESTIONS.

PMID- 18738054
TI  - PECCAVIMUS.

PMID- 18738055
TI  - County Societies.

PMID- 18738056
TI  - State Societies.

PMID- 18738057
TI  - San Francisco Hospital Colloquia.

PMID- 18738059
TI  - Lane Medical Lectures.

PMID- 18738058
TI  - Memorial Laboratory and Clinic Santa Barbara.

PMID- 18738060
TI  - Department of Pharmacy and Chemistry.

PMID- 18738061
TI  - "Pasteur" Made the Hero of a Play.

PMID- 18738063
TI  - THE DRUG ADDICT QUESTION.

PMID- 18738062
TI  - The San Francisco Hospital.

PMID- 18738064
TI  - JUSTICE VERSUS "SCIENCE.".

PMID- 18738065
TI  - IMPORTANT ANNOUNCEMENT.

PMID- 18738066
TI  - CHEERFUL NONSENSE.

PMID- 18738067
TI  - LIABILITY OF PATIENT FOR ACCIDENT TO NURSE.

PMID- 18738068
TI  - EDITORIAL COMMENT.

PMID- 18738069
TI  - MINIMUM WAGE FOR OFFICE WORKERS.

PMID- 18738070
TI  - LOS ANGELES AND SAN FRANCISCO PHYSICIANS SKIP THIS.

PMID- 18738072
TI  - INTESTINAL FLAGELLATES: A PLEA FOR THEIR PATHOGENICITY.

PMID- 18738071
TI  - NOTES ON ENCEPHALITIS LETHARGICA IN SAN FRANCISCO.

PMID- 18738073
TI  - A PLEA FOR THE EARLIER RECOGNITION OF SUBACUTE INFANTILE SCURVY.

PMID- 18738075
TI  - County Societies.

PMID- 18738074
TI  - A CASE OF TETANUS SUCCESSFULLY TREATED BY ANTITOXIN.

PMID- 18738076
TI  - San Francisco Colloquia.

PMID- 18738077
TI  - State Board of Medical Examiners.

PMID- 18738078
TI  - 1920 RESOLUTIONS.

PMID- 18738079
TI  - Question of Improving Business Methods and Increase of Fees.

PMID- 18738080
TI  - A Local Study of Trachoma.

PMID- 18738081
TI  - Present Problems in Appendicitis.

PMID- 18738082
TI  - INDUSTRIAL PHYSIOLOGY.

PMID- 18738084
TI  - ANNUAL TAX NOW DUE.

PMID- 18738083
TI  - MUNICIPAL EMERGENCY HOSPITAL RULES.

PMID- 18738085
TI  - Perforated Gastric and Duodenal Ulcers.

PMID- 18738086
TI  - Bone Formation and Bone Pathology.

PMID- 18738087
TI  - County Societies: Alameda.

PMID- 18738089
TI  - Editorial Comment.

PMID- 18738088
TI  - Hospital Service Department.

PMID- 18738091
TI  - HOSPITAL SERVICE.

PMID- 18738090
TI  - DOES INDUSTRIAL MEDICINE PAY?

PMID- 18738092
TI  - Clinical Department: Case Histories from the Children's Department, University of
      California Medical School and Hospitals.

PMID- 18738093
TI  - State Board of Medical Examiners.

PMID- 18738094
TI  - Hydrocephalic Epilepsy With Case Report.

PMID- 18738095
TI  - STATE BUREAU OF CHILD HYGIENE.

PMID- 18738096
TI  - CALIFORNIA'S MINERAL SPRINGS.

PMID- 18738097
TI  - MORE CHEERFUL NONSENSE.

PMID- 18738098
TI  - A CITY DIVIDED AGAINST ITSELF.

PMID- 18738100
TI  - BOTULISM.

PMID- 18738099
TI  - Editorial Comment.

PMID- 18738101
TI  - THE RADIOGRAPHIC STUDY OF THE ABDOMINAL ORGANS AFTER INFLATION OF THE PERITONEAL
      CAVITY.

PMID- 18738102
TI  - THE PRACTITIONER'S CONTRIBUTION TO EMBRYOLOGY.

PMID- 18738103
TI  - THE PROBLEM OF UTERINE CANCER.

PMID- 18738104
TI  - REFINEMENT OF COLORIMETRIC METHODS WITH SPECIAL REFERENCE TO INDIGO CARMINE AS A
      FUNCTIONAL TEST: A PRELIMINARY REPORT.

PMID- 18738105
TI  - EDDYISM, INDIANS AND MALARIA.

PMID- 18738106
TI  - THE MATTER OF PAY FOR MEDICAL SERVICE.

PMID- 18738107
TI  - State Medical Society.

PMID- 18738108
TI  - County Societies.

PMID- 18738110
TI  - Hospital Service Department: The Model Community Service Hospital.

PMID- 18738109
TI  - MEMORIAL ADDRESS.

PMID- 18738111
TI  - Clinical Department: Case Histories From the Children's Department University of
      California Medical School and Hospitals No. 2.

PMID- 18738112
TI  - Department of Pharmacy and Chemistry.

PMID- 18738113
TI  - Bureau of Child Hygiene: Minimum Standards for the Public Protection of the
      Health of Children and Mothers.

PMID- 18738114
TI  - State Board of Medical Examiners: Collected Clippings on Medical Law Enforcement.

PMID- 18738115
TI  - Correspondence.

PMID- 18738117
TI  - Medicine Before The Bench.

PMID- 18738116
TI  - County Societies.

PMID- 18738118
TI  - Department of Pharmacy and Chemistry.

PMID- 18738119
TI  - Clinical Department: Case Histories from the Children's Deparment, University of
      California Medical School and Hospitals.

PMID- 18738120
TI  - State Board of Medical Examiners: Collected Clippings on Medical Law Enforcement.

PMID- 18738121
TI  - STATE SOCIETY.

PMID- 18738122
TI  - CHARITY SHOULD BEGIN AT HOME.

PMID- 18738123
TI  - AN APPRECIATION.

PMID- 18738124
TI  - UNINTENTIONAL MISDEMEANOR OF HOSPITAL SUPERINTENDENTS AND PHYSICIANS.

PMID- 18738125
TI  - AUTOMOBILE FOR NURSE.

PMID- 18738126
TI  - HANFORD STOPS SPITTERS.

PMID- 18738127
TI  - NURSES NEEDED.

PMID- 18738128
TI  - DID WILEY EVER PRACTICE MEDICINE?

PMID- 18738130
TI  - THE ORGANIZATION AND MANAGEMENT OF HOSPITALS.

PMID- 18738129
TI  - BOTULISM.

PMID- 18738131
TI  - NEURO-OTOLOGY: ITS RELATION TO GENERAL MEDICINE.

PMID- 18738132
TI  - COMPARISON OF THE ACTION OF ROENTGEN RAYS AND RADIUM.

PMID- 18738133
TI  - REFRACTION AND MEDICINE.

PMID- 18738134
TI  - GOITER.

PMID- 18738135
TI  - CANCER OF THE EAR, NOSE AND THROAT.

PMID- 18738136
TI  - AVIATION'S DEBT TO MEDICINE.

PMID- 18738137
TI  - ABDUCENS PALSY-TRANSPLANTATION OF VERTICAL RECTI IN THREE CASES.

PMID- 18738138
TI  - THE TREATMENT OF FRESH AND UN-UNITED FRACTURES OF THE FEMORAL NECK.

PMID- 18738140
TI  - THE EXAMINATION AND CLASSIFICATION OF AVIATORS WITH SPECIAL REFERENCE TO THE
      EFFECTS OF HIGH ALTITUDES.

PMID- 18738139
TI  - WAR WOUNDS OF THE SINUSES WITH X-RAY PLATES.

PMID- 18738142
TI  - OUIJA BOARDS AND CULT CURES.

PMID- 18738141
TI  - IMPORTANT ANNOUNCEMENT BY THE PROGRAM COMMITTEE.

PMID- 18738144
TI  - CHIROPRACTORS DEFY LAW.

PMID- 18738143
TI  - DOCTOR C. A. L. REED LAUDS LEAGUE.

PMID- 18738145
TI  - THE LADY AND THE TIGER.

PMID- 18738146
TI  - Editorial Comment.

PMID- 18738147
TI  - BOARD AND STAFF ORGANIZATION.

PMID- 18738149
TI  - REVIEW OF 1918 CENSUS OF CAUSES OF DEATH.

PMID- 18738148
TI  - ORGANIZATION OF A METABOLISM UNIT.

PMID- 18738150
TI  - Received at Stanford Clinics.

PMID- 18738151
TI  - HATS OFF TO TRINITY COUNTY.

PMID- 18738153
TI  - County Societies.

PMID- 18738152
TI  - CUI BONO?

PMID- 18738154
TI  - Clinical Department: Case Histories from the Children's Department, University of
      California Medical School and Hospitals.

PMID- 18738156
TI  - State Board of Medical Examiners: Collected Clippings on Medical Law Enforcement.

PMID- 18738155
TI  - GLEANINGS FROM A YEAR OF COUNTRY PRACTICE.

PMID- 18738157
TI  - Medicine Before The Bench.

PMID- 18738158
TI  - COURT DECISION REGARDING LOCATION OF A TUBERCULOSIS HOSPITAL.

PMID- 18738159
TI  - Department of Pharmacy and Chemistry.

PMID- 18738160
TI  - CHIROPRACTOR FOUND GUILTY.

PMID- 18738161
TI  - DEPARTMENT STORES AND THE EPISCOPAL CHURCH.

PMID- 18738162
TI  - CALIFORNIA STATE MEDICAL SOCIETY ALL ABOARD FOR SANTA BARBARA.

PMID- 18738164
TI  - WOODCOCK'S "CULT EXPERTS".

PMID- 18738163
TI  - ARE CHIROPRACTORS ABOVE THE LAW?

PMID- 18738165
TI  - CANCER.

PMID- 18738167
TI  - $100,000 EDDIANSCIENSCHISM SUIT.

PMID- 18738166
TI  - TO WHOM IT MAY CONCERN.

PMID- 18738168
TI  - THE HOSPITAL EXECUTIVE.

PMID- 18738169
TI  - SURGICAL PATHOLOGY OF THE SEMINAL VESICLES.

PMID- 18738170
TI  - CLINICAL OBSERVATION AND TREATMENT OF 134 CASES OF CHRONIC PROSTATITIS.

PMID- 18738171
TI  - CONTRACTURE OF THE BLADDER-NECK AND OTHER OBSTRUCTIONS THEREAT, EXCLUSIVE OF
      PROSTATIC HYPERTROPHY AND CANCER, AND THEIR TREATMENT.

PMID- 18738172
TI  - THE LAY ANAESTHETIST.

PMID- 18738173
TI  - REPORT OF EYE LESIONS DUE TO FOCAL INFECTIONS.

PMID- 18738175
TI  - BORDERLINE TYPES OF SEBORRHOEIC DERMATITIS AND PSORIASIS.

PMID- 18738174
TI  - MULTIPLE PRIMARY TUMORS.

PMID- 18738176
TI  - SEPTIC LEPTO-MENINGITIS OF OTITIC ORIGIN. REPORT OF A CASE WITH RECOVERY.

PMID- 18738178
TI  - COMPARISON OF THE END RESULTS IN INTERMEDIATE AND SECONDARY PERINEORRHAPHIES.

PMID- 18738177
TI  - VACCINE TREATMENT OF TYPHOID.

PMID- 18738179
TI  - REPORT OF TWO CASES OF ETHMOIDAL MALIGNANCY.

PMID- 18738180
TI  - ACHYLIA GASTRICA-A NOTE REGARDING TREATMENT.

PMID- 18738181
TI  - SOME COMPARISONS BETWEEN WAR NEUROSES AND THOSE OF CIVIL LIFE.

PMID- 18738182
TI  - Clinical Department: Case Histories from the Children's Department, University of
      California Medical School and Hospitals.

PMID- 18738186
TI  - HOSPITAL HEADS FAVOR PSYCHOPATHIC HOSPITAL.

PMID- 18738187
TI  - ANOTHER FRAUD.

PMID- 18738188
TI  - DR. GRETH ON CHIROPRACTIC.

PMID- 18738189
TI  - HOW TRUE!

PMID- 18738191
TI  - WHAT THE DOCTORS THINK OF THE INDEMNITY DEFENSE FUND.

PMID- 18738192
TI  - Medicine Before The Bench.

PMID- 18738193
TI  - County Societies.

PMID- 18738194
TI  - The Reason Why Twelve Patients Entered the Sanatorium Too Late.

PMID- 18738195
TI  - For Discharged Soldiers.

PMID- 18738196
TI  - BETTER HEALTH.

PMID- 18738197
TI  - NEW MINIMUM FEES FOR INDUSTRIAL ACCIDENT WORK.

PMID- 18738198
TI  - DOCTORS TO DEFEAT "QUACK" SOLONS.

PMID- 18738199
TI  - THE ROLE OF THE PHYSICIAN IN INDUSTRIAL MEDICINE.

PMID- 18738200
TI  - THE LAY ANESTHETIST.

PMID- 18738201
TI  - HUBLEY AND BROOKS GO ON FOREVER.

PMID- 18738202
TI  - CONCERNING OSTEOPATHY.

PMID- 18738203
TI  - Editorial Comment.

PMID- 18738205
TI  - MALINGERING: ITS RELATION TO THE DOCTOR.

PMID- 18738204
TI  - THE X-RAY AS AN AID IN DIAGNOSIS OF NON-TUBERCULAR PULMONARY CONDITIONS.

PMID- 18738206
TI  - A NEW FORM OF WEIGHT CHART FOR INFANTS.

PMID- 18738207
TI  - Clinical Department: Case Histories from the Children's Department of the
      University of California Medical School and Hospitals.

PMID- 18738208
TI  - County Societies.

PMID- 18738209
TI  - WHAT ONE READER THINKS.

PMID- 18738210
TI  - DIET IN HAY FEVER.

PMID- 18738211
TI  - Department of Pharmacy and Chemistry.

PMID- 18738212
TI  - Medicine Before the Bench.

PMID- 18738213
TI  - Medical Items in California Press.

PMID- 18738214
TI  - State Board of Medical Examiners: Regular Meeting.

PMID- 18738215
TI  - DOCTORS, ATTENTION! IS YOUR STATE TAX PAID?

PMID- 18738216
TI  - THE EPISCOPAL CHURCH AND THE DOCTOR.

PMID- 18738217
TI  - EDDIAN SCIENCE SINGULAR SANITARIUM "CERTAIN CASES NOT RECEIVED.".

PMID- 18738218
TI  - PUBLIC HEALTH CONVENTION AT SAN FRANCISCO, SEPTEMBER 13-17.

PMID- 18738219
TI  - CHIROPRACTIC S. O. S.

PMID- 18738220
TI  - SOME PRACTICAL FEATURES OF HEART DISEASE.

PMID- 18738221
TI  - Editorial Comment.

PMID- 18738222
TI  - NEGLECTED OPPORTUNITIES.

PMID- 18738223
TI  - CAMPAIGN ISSUES.

PMID- 18738224
TI  - THE FORMICATION TEST IN PERIPHERAL NERVE INJURIES-ITS INTERPRETATION.

PMID- 18738225
TI  - EXPERIENCES IN TESTICLE TRANSPLANTATION.

PMID- 18738226
TI  - URETERO-PYELOGRAPHY AND CYSTOGRAPHY: THEIR PRESENT STATUS AND SAFETY AS
      DIAGNOSTIC AGENTS.

PMID- 18738227
TI  - THE PROBLEM OF THE HOSPITAL DIETITIAN.

PMID- 18738229
TI  - PROFESSIONAL ETHICS.

PMID- 18738228
TI  - CARE AND USE OF NEW ARSENICALS.

PMID- 18738230
TI  - DIAGNOSIS OF SARCOMA VERIFIED.

PMID- 18738231
TI  - ANOTHER GEM OF PUREST RAY.

PMID- 18738232
TI  - ACKNOWLEDGMENT OF VIENNA RELIEF FUND.

PMID- 18738234
TI  - County Societies.

PMID- 18738233
TI  - POLICY OF THE EPISCOPAL CHURCH IN HEALTH MATTERS.

PMID- 18738237
TI  - Department of Pharmacy and Chemistry.

PMID- 18738236
TI  - Report from A. M. A: Report of Dr. Van Zwalenburg, California Delegate to A. M.
      A.

PMID- 18738238
TI  - Clinical Department: Case Histories from the Children's Department, University of
      California Medical School and Hospitals.

PMID- 18738239
TI  - MOUNT ZION HOSPITAL NOTES SAN FRANCISCO.

PMID- 18738240
TI  - Why We Believe in Proper Medical Education.

PMID- 18738242
TI  - Medical Items in California Press: Dr. James H. Thompson Arrested Again.

PMID- 18738241
TI  - Medicine Before the Bench.

PMID- 18738243
TI  - COLLECTED CLIPPINGS ON MEDICAL LAW ENFORCEMENT.

PMID- 18738244
TI  - CONSTITUTIONALITY OF MEDICAL PRACTICE ACT ATTACKED AND AFFIRMED.

PMID- 18738245
TI  - THE NOVEMBER BALLOT.

PMID- 18738246
TI  - HEALTH INSURANCE AND PHYSICIANS.

PMID- 18738247
TI  - THE EDDIAN FRATRICIDAL WAR.

PMID- 18738248
TI  - CHRISTIAN SCIENCE HEALERS EXEMPT FROM LICENSE TAX.

PMID- 18738250
TI  - Editorial Comment.

PMID- 18738249
TI  - POLITICS AND HEALTH.

PMID- 18738251
TI  - WHAT ARE YOU DOING TO DEFEAT ANTI-HEALTH AND ANTI-MEDICAL LEGISLATION?

PMID- 18738253
TI  - THE TREATMENT OF INDUSTRIAL DISABILITIES INVOLVING THE SPINAL COLUMN.

PMID- 18738252
TI  - INFANT MORTALITY IN SAN FRANCISCO IN 1919.

PMID- 18738254
TI  - DELAYED ULNAR PALSY FOLLOWING ELBOW INJURY.

PMID- 18738255
TI  - THE TREATMENT OF CHRONIC AMEBIC DYSENTERY CYST CARRIERS.

PMID- 18738256
TI  - SHORTAGE OF TRAINED NURSES.

PMID- 18738258
TI  - County Societies.

PMID- 18738257
TI  - FROM A. M. A. DELEGATE.

PMID- 18738259
TI  - THE HEALING POWER OF PRAYER.

PMID- 18738260
TI  - Clinical Department: Case 2 for Diagnosis.

PMID- 18738261
TI  - CASE HISTORIES FROM THE CHILDREN'S DEPARTMENT UNIVERSITY OF CALIFORNIA MEDICAL
      SCHOOL AND HOSPITALS.

PMID- 18738263
TI  - Department of Pharmacy and Chemistry.

PMID- 18738262
TI  - Medicine Before the Bench.

PMID- 18738264
TI  - State Board of Medical Examiners: Collected Clippings on Medical Law Enforcement.

PMID- 18738265
TI  - Collected Clippings in Press: The Fountain-Head of Chiropractic; What of its
      Product?

PMID- 18738267
TI  - RUNNERS! HAVE YOU MET THEM?

PMID- 18738266
TI  - VOTE NO ON NUMBER 5 THE CHIROPRACTIC INITIATIVE.

PMID- 18738268
TI  - THE THERAPEUTIC USE OF OXYGEN.

PMID- 18738269
TI  - Editorial Comment.

PMID- 18738270
TI  - REASONS FOR ERRORS IN DIAGNOSIS.

PMID- 18738271
TI  - PREHISTORIC TREPHINING OF THE FRONTAL SINUS.

PMID- 18738272
TI  - ECLAMPSIA WITH SEVENTY CONVULSIONS; RECOVERY.

PMID- 18738273
TI  - THE SURGICAL TREATMENT OF ACUTE OTITIS MEDIA IN CHILDREN, WITH REPORT OF FIFTY
      CONSECUTIVE CASES.

PMID- 18738274
TI  - HOOKWORM AND AMOEBIASIS IN CALIFORNIA.

PMID- 18738275
TI  - BASAL METABOLISM IN THYROID DISEASE, AS AN AID TO DIAGNOSIS AND TREATMENT, WITH
      NOTES ON THE UTILITY OF THE MODIFIED TISSOT APPARATUS.

PMID- 18738276
TI  - BEWARE THE SWINDLER.

PMID- 18738277
TI  - Correspondence.

PMID- 18738278
TI  - THE PHYSICIAN'S RESPONSIBILITY.

PMID- 18738279
TI  - WELL DESERVED TRIBUTES.

PMID- 18738280
TI  - County Societies.

PMID- 18738281
TI  - Clinical Department.

PMID- 18738282
TI  - ILLUSTRATING THE NEED FOR A STATE BOARD OF MEDICAL EXAMINERS.

PMID- 18738283
TI  - A WELL-DESERVED ENCOMIUM.

PMID- 18738284
TI  - Medicine Before the Bench.

PMID- 18738286
TI  - Jewish Medical Association of Palestine.

PMID- 18738285
TI  - Collected Clippings in Press.

PMID- 18738287
TI  - ATTENTION, PHYSICIANS, VOTERS!

PMID- 18738288
TI  - THE HEALTH CONVENTION.

PMID- 18738290
TI  - RURAL HEALTH AND RECREATION.

PMID- 18738289
TI  - SERVICE.

PMID- 18738291
TI  - Editorial Comment.

PMID- 18738292
TI  - ANOTHER ROYAL ROAD TO LEARNING.

PMID- 18738293
TI  - SMALLPOX-A PLEA FOR VACCINATION.

PMID- 18738294
TI  - NOTES ON SKIN DISEASES OBSERVED AT THE LETTERMAN GENERAL HOSPITAL.

PMID- 18738295
TI  - THE SIGNIFICANCE OF THE SCIENCE OF OBSTETRICS AND GYNECOLOGY CONSIDERED AS
      SPECIALTIES.

PMID- 18738296
TI  - THE PRESENT STATUS OF ANESTHESIOLOGY AND THE ANESTHETIST.

PMID- 18738298
TI  - CALIFORNIANS ON THE ITALIAN FRONT-HISTORICAL.

PMID- 18738297
TI  - SOME RECOLLECTIONS AND OPHTHALMOLOGIC OBSERVATIONS FROM SERVICE IN THE A. E. F.
      IN FRANCE.

PMID- 18738299
TI  - END RESULTS OF RADICAL AND CONSERVATIVE PELVIC SURGERY.

PMID- 18738300
TI  - Bar Association Says Vote Yes on No. 3.

PMID- 18738301
TI  - Clinical Department: Probable Smallpox-Report of Case.

PMID- 18738303
TI  - State Society.

PMID- 18738302
TI  - CASE HISTORIES FROM THE CHILDREN'S DEPARTMENT, UNIVERSITY OF CALIFORNIA MEDICAL
      SCHOOL AND HOSPITALS.

PMID- 18738305
TI  - State Board of Medical Examiners: Legal Department.

PMID- 18738304
TI  - County Societies.

PMID- 18738307
TI  - CLINICAL CONGRESS OF SURGEONS.

PMID- 18738306
TI  - Collected Clippings on Medical Law Enforcement.

PMID- 18738309
TI  - OPHTHALMOLOGY VS. OPTOMETRY.

PMID- 18738308
TI  - INDIVIDUALISM IN MEDICINE.

PMID- 18738310
TI  - MALPRACTICE-INDEMNITY DEFENSE FUND.

PMID- 18738311
TI  - COUNCIL OF SOCIAL AND HEALTH AGENCIES.

PMID- 18738312
TI  - THE ROENTGEN DIAGNOSIS AND LOCALIZATION OF PEPTIC ULCER.

PMID- 18738313
TI  - THE "FRINGES" OF MEDICINE.

PMID- 18738314
TI  - NASAL PLASTIC SURGERY.

PMID- 18738315
TI  - THE MODERN TREATMENT OF SYPHILIS OF THE CENTRAL NERVOUS SYSTEM.

PMID- 18738316
TI  - A NOTE ON THE QUALITY OF SOME DRUG PREPARATIONS SOLD IN AND AROUND LOS ANGELES.

PMID- 18738317
TI  - County Societies.

PMID- 18738318
TI  - State Society.

PMID- 18738319
TI  - Department of Pharmacy and Chemistry.

PMID- 18738320
TI  - THE USE OF BENZYL-BENZOATE IN SEASICKNESS.

PMID- 18738321
TI  - Clinical Department: Report of Extensive Fracture and Dislocation of 5th And 6th
      Vertebrae with Recovery.

PMID- 18738322
TI  - CASE HISTORIES FROM THE CHILDREN'S DEPARTMENT, UNIVERSITY OF CALIFORNIA MEDICAL
      SCHOOL AND HOSPITALS.

PMID- 18738324
TI  - Collected Clippings on Medical Law Enforcement.

PMID- 18738323
TI  - Status of Venereal Disease Control: Report of Committee on Control of Syphilis
      and Gonorrhea.

PMID- 18738325
TI  - AN ANCIENT OPINION ON THE PHYSICIAN.

PMID- 18738326
TI  - CORDIAL CONGRATULATIONS, CALIFORNIA!

PMID- 18738328
TI  - TYROQUACKTORS RAMPANT.

PMID- 18738327
TI  - REFLECTIONS AFTER THE BATTLE.

PMID- 18738329
TI  - RAGE OF POLITICAL OSTEOPATHS.

PMID- 18738331
TI  - A GROSS MISTAKE.

PMID- 18738330
TI  - THE EDUCATION AND TRAINING OF THE MODERN SURGEON.

PMID- 18738333
TI  - MAGNET EXTRACTION OF FOREIGN BODIES WITH PARTICULAR REFERENCE TO THE IMPORTANCE
      OF ACCURATE LOCALIZATION.

PMID- 18738332
TI  - COMPULSORY CHESTNUTS.

PMID- 18738334
TI  - RETROVERSIONS OF THE UTERUS.

PMID- 18738335
TI  - NOTES ON PATHOLOGICAL REFLEXES.

PMID- 18738336
TI  - RECONSTRUCTIVE SURGERY OF THE SHOULDER.

PMID- 18738337
TI  - ELECTROCARDIOGRAPHIC STUDIES OF THE HEART.

PMID- 18738338
TI  - CONTROL OF TUBERCULOSIS.

PMID- 18738339
TI  - VERBUM SAP.

PMID- 18738340
TI  - COUNTRY GENTLEMAN BELIES THE NAME.

PMID- 18738341
TI  - A DISCRIMINATING FRIEND.

PMID- 18738342
TI  - State Society.

PMID- 18738343
TI  - A CONSTRUCTIVE SUGGESTION.

PMID- 18738345
TI  - County Societies.

PMID- 18738344
TI  - METHODISTS FOR VIVISECTION.

PMID- 18738346
TI  - Clinical Department: Case Histories from the Children's Department, University of
      California Medical School and Hospitals.

PMID- 18738347
TI  - Department of Pharmacy and Chemistry.

PMID- 18738348
TI  - Collected Clippings on Medical Law Enforcement.

PMID- 18738349
TI  - THE LEGISLATURE.

PMID- 18738350
TI  - TITHES.

PMID- 18738351
TI  - A Plea for Better Fracture Results.

PMID- 18738352
TI  - Practical Points in Using Thomas Splints.

PMID- 18738353
TI  - Pyelitis and Pyelonephritis, Some Observations from the Clinical and Laboratory
      Findings in.

PMID- 18738355
TI  - Genito-Urinary Tract Associated with Active Pulmonary Tuberculosis.

PMID- 18738354
TI  - Improved Incision for the Fredet Rammstedt Operation.

PMID- 18738357
TI  - MEDICAL FREEDOM.

PMID- 18738356
TI  - Vesico-Intestinal Fistula.

PMID- 18738358
TI  - VANITAS VANITATUM.

PMID- 18738359
TI  - Ureteral Transplants for Obstruction of the Lower Ureter.

PMID- 18738360
TI  - Spinal Defects and Pain Occurring in Relation to Ocular Disease.

PMID- 18738362
TI  - Bronchial Asthma, Etiology of 150 Cases.

PMID- 18738361
TI  - Arthritis, A Group Study of 300 Cases.

PMID- 18738363
TI  - $100,000 TO FIGHT VIVISECTION.

PMID- 18738364
TI  - FUNDAMENTALS OF NUTRITION.

PMID- 18738365
TI  - A STUDY OF NASAL CONDITIONS OCCURRING IN BRONCHIAL ASTHMA.

PMID- 18738366
TI  - El Retiro, The New School for Girls.

PMID- 18738367
TI  - CHIROPRACTICALLY SPEAKING.

PMID- 18738368
TI  - A CORRECTION.

PMID- 18738369
TI  - CHIROPRACTIC OPEN SEASON ENDS.

PMID- 18738370
TI  - Clinical Department: AMEBIC GALL BLADDER INFECTIONS WITH OPERATION.

PMID- 18738371
TI  - CASE HISTORIES FROM THE CHILDREN'S DEPARTMENT, UNIVERSITY OF CALIFORNIA MEDICAL
      SCHOOL AND HOSPITAL.

PMID- 18738372
TI  - Collected Clippings on Medical Law Enforcement: The People of the State of
      California vs. Galen R. Hickok.

PMID- 18738374
TI  - The Present Nursing Situation.

PMID- 18738373
TI  - PROBLEMS OF ENFORCEMENT OF THE MEDICAL ACT.

PMID- 18738375
TI  - THE OATH OF HIPPOCRATES.

PMID- 18738376
TI  - INTERVIEW YOUR SENATOR AND ASSEMBLYMAN.

PMID- 18738377
TI  - BOARD OF MEDICAL EXAMINERS ABOLISHED BY ASSEMBLY BILL 347.

PMID- 18738378
TI  - DUE PROCESS OF LAW WHAT THE CULVER DECISION MEANS.

PMID- 18738379
TI  - IPECAC-THE PANCEA AND CURE-ALL.

PMID- 18738380
TI  - FULTON'S COMPOUNDS.

PMID- 18738381
TI  - Editorial Comment.

PMID- 18738383
TI  - RELATIONSHIP BETWEEN TRAUMA AND MALIGNANT DISEASE FROM AN INDUSTRIAL VIEWPOINT.

PMID- 18738382
TI  - CONCERNING THE SIZE OF WOMEN: PRELIMINARY NOTE WITH SPECIAL REFERENCE TO HEIGHT.

PMID- 18738384
TI  - HOW CAN MEDICAL SERVICE BE IMPROVED?

PMID- 18738386
TI  - URINARY INCONTINENCE AND ITS OPERATIVE REPAIR.

PMID- 18738385
TI  - BILATERAL NEPHROLITHIASIS.

PMID- 18738387
TI  - INDUSTRIAL MEDICINE.

PMID- 18738388
TI  - THE INDUSTRIAL SURGEON, WHAT HE IS-WHAT HE CAN BE-WHAT HE SHOULD BE.

PMID- 18738389
TI  - DEFORMITIES OF THE HAND ACQUIRED AFTER ACCIDENTS.

PMID- 18738390
TI  - EXAMINATION OF EMPLOYEES IN INDUSTRY.

PMID- 18738391
TI  - ROENTGEN TREATMENT OF UTERINE HEMORRHAGE.

PMID- 18738392
TI  - HEAT THE MOST PRACTICAL AND PROMISING TREATMENT IN UTERINE CARCINOMA.

PMID- 18738393
TI  - NASAL CATARRH.

PMID- 18738394
TI  - CHAIRMAN'S ADDRESS ADVANCE IN BUSINESS METHODS.

PMID- 18738395
TI  - WE HEARTILY AGREE.

PMID- 18738396
TI  - VENEREAL DISEASE CONTROL.

PMID- 18738398
TI  - Clinical Department: CASE HISTORIES FROM THE CHILDREN'S DEPARTMENT, UNIVERSITY OF
      CALIFORNIA MEDICAL SCHOOL AND HOSPITALS.

PMID- 18738397
TI  - County Societies.

PMID- 18738399
TI  - Deaths.

PMID- 18738401
TI  - RECENT DEVELOPMENTS IN RADIUM THERAPY.

PMID- 18738400
TI  - STIFFNESS IN THE EXTREMITIES FOLLOWED BY ACCIDENT AND INJURY.

PMID- 18738402
TI  - SURGERY OF THE CHEST.

PMID- 18738403
TI  - SOME FURTHER EXPERIENCES IN THE TECHNIC, NON-OPERATIVE, PRE-OPERATIVE AND POST
      OPERATIVE TREATMENT OF SUPRAPUBIC PROSTATECTOMY CASES.

PMID- 18738404
TI  - POST-MATURITY OF THE FOETUS.

PMID- 18738405
TI  - LOW HAEMOGLOBIN IN OUR SURGICAL CASES.

PMID- 18738406
TI  - CLIMACTERIC HYPERTENSION.

PMID- 18738408
TI  - County Societies.

PMID- 18738407
TI  - TEETH, TONSILS AND SINUSES.

PMID- 18738409
TI  - State Society.

PMID- 18738411
TI  - Clinical Department: GALL BLADDER FOCALIZATION AND ITS NON-SURGICAL TREATMENT.

PMID- 18738410
TI  - CASE HISTORIES FROM THE CHILDREN'S DEPARTMENT, UNIVERSITY OF CALIFORNIA MEDICAL
      SCHOOL AND HOSPITALS.

PMID- 18738412
TI  - WHAT DO YOU GET OUT OF THE STATE MEDICAL SOCIETY?

PMID- 18738413
TI  - THE NEED FOR AUTOPSIES.

PMID- 18738414
TI  - ASSEMBLY BILL 72.

PMID- 18738415
TI  - MUNICIPAL TUBERCULOSIS PROGRAM.

PMID- 18738417
TI  - EPIDEMIC SMALLPOX.

PMID- 18738416
TI  - A BATTLESHIP FOR PUBLIC HEALTH.

PMID- 18738419
TI  - EDDIANSIGNOPRACTORS.

PMID- 18738418
TI  - Editorial Comment.

PMID- 18738420
TI  - DOCTORS AS HEALTH ADVISERS.

PMID- 18738421
TI  - SUCCESS: AS APPLIED TO UROLOGY.

PMID- 18738422
TI  - A NEW SECRETARY.

PMID- 18738423
TI  - ALL ABOARD FOR SAN DIEGO.

PMID- 18738424
TI  - RADIOLOGY IS A MEDICAL SPECIALTY.

PMID- 18738425
TI  - SAN DIEGO SOCIAL PROGRAM.

PMID- 18738426
TI  - CARE OF CRIPPLED CHILDREN.

PMID- 18738428
TI  - THE COMMITMENT OF THE INSANE.

PMID- 18738427
TI  - HOSPITALS, ATTENTION!

PMID- 18738429
TI  - ANTHROPOLOGY AND AMERICANISM.

PMID- 18738430
TI  - THE REVERIES OF A GENERAL PRACTITIONER.

PMID- 18738431
TI  - INDICATIONS FOR INFUSION OF BLOOD SUBSTITUTES AND TRANSFUSION OF BLOOD IN CASES
      OF TRAUMATIC HEMORRHAGE AND SHOCK.

PMID- 18738433
TI  - EPISODIC MENTAL STATES AND BORDER-LINE CONDITIONS IN PSYCHIATRY.

PMID- 18738432
TI  - FRACTURED FEMUR.

PMID- 18738434
TI  - FOR BETTER TREATMENT FOR CRIPPLED CHILDREN.

PMID- 18738435
TI  - EARLY DIAGNOSIS OF PULMONARY TUBERCULOSIS.

PMID- 18738436
TI  - MODERN RADIOTHERAPY.

PMID- 18738437
TI  - PET AIREDALE UNDERGOES SERIOUS OPERATION: TWILIGHT SLEEP ADMINISTERED WHILE DOG'S
      SPINAL COLUMN IS STRETCHED.

PMID- 18738438
TI  - RESIGNATION OF THE EDITOR.

PMID- 18738439
TI  - A WORTHY APPEAL.

PMID- 18738441
TI  - County Societies.

PMID- 18738440
TI  - A SECTION ON DERMATOLOGY.

PMID- 18738442
TI  - A Correction.

PMID- 18738443
TI  - Department of Pharmacy and Chemistry.

PMID- 18738444
TI  - Clinical Department: FILARIASIS.

PMID- 18738445
TI  - CASE HISTORIES FROM THE CHILDREN'S DEPARTMENT, UNIVERSITY OF CALIFORNIA MEDICAL
      SCHOOL AND HOSPITALS.

PMID- 18738446
TI  - ACUTE PERFORATION OF DUODENAL ULCER: With Report of Eight Cases.

PMID- 18738447
TI  - Deaths.

PMID- 18738448
TI  - A STRONG STATE SOCIETY.

PMID- 18738449
TI  - THE GROWING RECOGNITION OF ANESTHESIA.

PMID- 18738450
TI  - ARTIFICIAL IMMUNITY IN DIPHTHERIA.

PMID- 18738451
TI  - CONDUCT AND VALUE OF AUTOPSIES.

PMID- 18738452
TI  - THE SALVAGING OF CIVILIZATION.

PMID- 18738453
TI  - THE PHYSICIAN AND SOCIAL AGENCIES.

PMID- 18738454
TI  - Editorial Comment.

PMID- 18738455
TI  - KEEP THE TUBERCULOSIS POOR IN THEIR HOME STATE.

PMID- 18738456
TI  - SMALLPOX A QUARANTINABLE DISEASE.

PMID- 18738457
TI  - POISON OAK DERMATITIS: A SPECIFIC TREATMENT.

PMID- 18738458
TI  - RESULTS OF THE WASSERMANN TEST ON 1518 MEN AT SAN QUENTIN PRISON.

PMID- 18738459
TI  - ANTE AND POST-OPERATIVE TREATMENT.

PMID- 18738460
TI  - AMEBA-LIKE LEUCOCYTES IN NORMAL BLOOD AND IN PUS.

PMID- 18738461
TI  - PLASTER CAST IMMOBILIZATION OF FRACTURES PRIOR TO OPEN OPERATION FOR REDUCTION OF
      SAME.

PMID- 18738462
TI  - TRAUMA-ITS RELATION TO NERVOUS DISEASES OF UNDETERMINED PATHOLOGY.

PMID- 18738463
TI  - AN ESSENTIAL IN RECONSTRUCTIVE SURGERY-;ATRAUMATIC' TECHNIQUE.

PMID- 18738464
TI  - ACUTE BRAIN INJURIES.

PMID- 18738465
TI  - THE NEUROLOGICAL ASPECTS OF VISCEROPTOSIS.

PMID- 18738466
TI  - THE AIRPLANE WAITS.

PMID- 18738467
TI  - County Societies.

PMID- 18738468
TI  - WHY! OH! WHY!

PMID- 18738469
TI  - St. Joseph's Hospital, San Diego.

PMID- 18738470
TI  - CASE HISTORIES FROM THE CHILDREN'S DEPARTMENT, UNIVERSITY OF CALIFORNIA MEDICAL
      SCHOOL AND HOSPITALS.

PMID- 18738471
TI  - LEAGUE LUNCHEON AT CORONADO.

PMID- 18738472
TI  - PACIFIC COAST MEDICINE.

PMID- 18738473
TI  - MINERS' CONSUMPTION.

PMID- 18738474
TI  - COMMERCIAL VITAMIN PREPARATIONS.

PMID- 18738475
TI  - THE CALL OF SERVICE.

PMID- 18738476
TI  - NARCOTIC LAW INSTRUCTIONS.

PMID- 18738478
TI  - MEDICAL ASPECTS OF VISCEROPTOSIS.

PMID- 18738477
TI  - DIET AND HEALTH WITH KEY TO THE CALORIES.

PMID- 18738479
TI  - ANOTHER PROBLEM IN SURGERY.

PMID- 18738480
TI  - CHAIRMAN'S ADDRESS-SECTION ON PEDIATRICS CALIFORNIA STATE MEDICAL SOCIETY.

PMID- 18738481
TI  - THE TREATMENT OF TUBERCULOSIS WITH PARTIGENS (AFTER MUCH-DEYCKE.

PMID- 18738482
TI  - THE PROTECTION OF THE PERINEUM BY EPISIOTOMY IN DELIVERY AT TERM.

PMID- 18738483
TI  - PROBLEMS IN PLASTIC SURGERY.

PMID- 18738484
TI  - THE INFLUENCE OF ADRENALIN ON NEPHRITIS AND ITS COMPLICATIONS BY INJECTION INTO
      THE KIDNEYS.

PMID- 18738485
TI  - NEW OBESITY CURES FOR OLD OR THE CHIROPRACTIC THRUST.

PMID- 18738486
TI  - AMEBIC ABSCESS OF THE LIVER.

PMID- 18738487
TI  - TREATMENT OF BLADDER TUMORS BY RADIATION AND FULGURATION.

PMID- 18738489
TI  - ORGANIZED MEDICINE FOR THE MASSES A FEATURE OF PRESENTDAY MEDICAL PRACTICE.

PMID- 18738488
TI  - PERIPHERAL NERVE SURGERY.

PMID- 18738491
TI  - CLINICAL USEFULNESS OF ORTHOCARDIOGRAM AND CARDIAC PATTERN.

PMID- 18738490
TI  - THE ENDOCRINES AND THEIR INFLUENCE ON THE SKIN.

PMID- 18738492
TI  - County Societies.

PMID- 18738494
TI  - THE GRACELESS CHIRO.

PMID- 18738493
TI  - A NEW THEORY OF THE CIRCULATION.

PMID- 18738495
TI  - CASE HISTORIES FROM THE CHILDREN'S DEPARTMENT, UNIVERSITY OF CALIFORNIA MEDICAL
      SCHOOL AND HOSPITALS.

PMID- 18738496
TI  - "NEUROTIC" ASTHMA.

PMID- 18738498
TI  - Deaths.

PMID- 18738497
TI  - WILLIAM BREAKEY LEWITT.

PMID- 18738499
TI  - ATTACKS UPON SCIENTIFIC MEDICINE.

PMID- 18738500
TI  - HOSPITAL BETTERMENT IN CALIFORNIA.

PMID- 18738501
TI  - PHYSIOTHERAPY.

PMID- 18738502
TI  - LEGAL LIABILITY FOR TRANSMITTING INFECTION.

PMID- 18738503
TI  - PRESIDENT'S ADDRESS.

PMID- 18738504
TI  - RESPONSIBILITY FOR STATEMENTS AND CONCLUSIONS IN ORIGINAL ARTICLES.

PMID- 18738505
TI  - SOME ASPECTS OF PERNICIOUS ANEMIA AND ITS TREATMENT.

PMID- 18738506
TI  - PERIPHERAL NERVE SURGERY.

PMID- 18738507
TI  - AMOEBIC ABCESS OF LIVER WITH PULMONARY SEQUELAE.

PMID- 18738508
TI  - URETERAL DIVERTICULA.

PMID- 18738509
TI  - ONE HUNDRED CONSECUTIVE PERINEAL PROSTATECTOMIES: A CRITICAL REVIEW.

PMID- 18738510
TI  - SOME OBSERVATIONS IN CASES OF FRACTURED SKULLS SEEN IN THE SAN FRANCISCO
      EMERGENCY HOSPITALS.

PMID- 18738511
TI  - CONGENITAL PYLORIC STENOSIS.

PMID- 18738513
TI  - CHRONIC DILATATION OF THE DUODENUM.

PMID- 18738512
TI  - SURGICAL RESULTS FROM AN ECONOMIC STANDPOINT.

PMID- 18738514
TI  - ACUTE SUPPURATIVE THYROIDITIS.

PMID- 18738515
TI  - FOCAL INFECTION.

PMID- 18738516
TI  - County Societies.

PMID- 18738518
TI  - Clinical Department: CASE HISTORIES FROM THE CHILDREN'S DEPARTMENT UNIVERSITY OF
      CALIFORNIA MEDICAL SCHOOL AND HOSPITALS.

PMID- 18738517
TI  - Department of Pharmacy and Chemistry.

PMID- 18738519
TI  - VACANCIES IN THE MEDICAL CORPS OF THE NAVY.

PMID- 18738520
TI  - CERTIFICATES TO PRACTICE THE HEALING ART.

PMID- 18738521
TI  - PACIFIC COAST ASSOCIATION OF ANESTHETISTS.

PMID- 18738522
TI  - Deaths.

PMID- 18738524
TI  - SILVER ARSPHENAMINE.

PMID- 18738523
TI  - ORTHODIAGRAPHY.

PMID- 18738525
TI  - GROUP MEDICINE.

PMID- 18738526
TI  - EXTENSION WORK OF THE STATE MEDICAL SOCIETY.

PMID- 18738527
TI  - ETHICS OF ADVERTISING.

PMID- 18738528
TI  - EPIDEMIC ENCEPHALITIS.

PMID- 18738529
TI  - THE DIAGNOSIS OF HYPOTHYROIDISM.

PMID- 18738530
TI  - PERSONAL EXPERIENCE WITH THE USE OF ARTIFICIAL PNEUMOTHORAX IN THE TREATMENT OF
      PULMONARY DISEASE.

PMID- 18738531
TI  - MONTHLY FLUCTUATIONS IN THE NORMAL METABOLIC RATES OF MEN AND WOMEN.

PMID- 18738532
TI  - TICS, AND THEIR TREATMENT.

PMID- 18738533
TI  - CHRONIC TROCHANTERIC BURSITIS.

PMID- 18738534
TI  - MENINGITIC EPILEPSY.

PMID- 18738535
TI  - CHRONIC ARTHRITIS.

PMID- 18738537
TI  - A USEFUL APPARATUS IN PHYSIO-THERAPY.

PMID- 18738536
TI  - SKIN RASHES IN EXOPHTHALMIC GOITRE.

PMID- 18738538
TI  - County Societies.

PMID- 18738539
TI  - Medicine Before the Bench.

PMID- 18738540
TI  - Commission on Milk Standards: UNITED STATES PUBLIC HEALTH SERVICE.

PMID- 18738541
TI  - SPARE THE OX.

PMID- 18738543
TI  - NEW PUBLIC HEALTH SERVICE HOSPITALS.

PMID- 18738542
TI  - DECAYED TEETH AND CHILDREN'S DISEASES.

PMID- 18738544
TI  - PACIFIC COAST ORTHOPEDIC ASSOCIATION.

PMID- 18738545
TI  - THE CALIFORNIA STATE HOMEOPATHIC MEDICAL SOCIETY.

PMID- 18738546
TI  - NARCOTIC LAW.

PMID- 18738547
TI  - Deaths.

PMID- 18738548
TI  - SHOULD THE PATIENT HAVE THE RIGHT OF CHOICE OF PHYSICIAN?

PMID- 18738549
TI  - MEDICAL EDUCATION.

PMID- 18738550
TI  - ORAL RADIOLOGY.

PMID- 18738552
TI  - THE RELATIONSHIP BETWEEN THE STATE AND THE PHYSICIAN IN ENGLAND.

PMID- 18738551
TI  - ADVERTISING MEDICINE.

PMID- 18738553
TI  - THE INFLUENCE OF CLIMATE ON TUBERCULOSIS.

PMID- 18738554
TI  - THE CALIFORNIA ASSOCIATION OF MEDICAL SOCIAL WORKERS.

PMID- 18738555
TI  - THE CALIFORNIA ASSOCIATION OF RADIOGRAPHERS.

PMID- 18738557
TI  - THE ANESTHESIOLOGY SITUATION IN CALIFORNIA.

PMID- 18738556
TI  - THE USE OF THE D'ARSONVAL METHOD OF COAGULATION NECROSIS FOR THE REMOVAL OF
      IMMENSE INTRAVESICAL OUTGROWTHS OF THE PROSTRATE, SIMPLE OR MALIGNANT.

PMID- 18738558
TI  - A PRELIMINARY REPORT OF AN INVESTIGATION INTO THE OXYGEN PERCENTAGES OF NITROUS
      OXIDE-OXYGEN ANESTHESIA.

PMID- 18738560
TI  - ACUTE LYMPHATIC LEUKEMIA WITH SPECIAL REFERENCE TO THROAT CONDITIONS-REPORT OF A
      CASE.

PMID- 18738559
TI  - CONDITIONS OF INDUSTRIAL ACCIDENT PRACTICE IN CALIFORNIA.

PMID- 18738561
TI  - PRECANCEROUS LESIONS OF THE UTERUS.

PMID- 18738562
TI  - THE VALUE OF BASAL METABOLISM ESTIMATIONS IN CASES WITH LOWERED METABOLISM.

PMID- 18738563
TI  - RESTORATION OF FUNCTION IN ACQUIRED HAND DEFORMITIES.

PMID- 18738565
TI  - THE ETIOLOGY OF PARENCHYMATOUS NEPHRITIS.

PMID- 18738564
TI  - THE IMPORTANCE OF THE VEGETATIVE SYSTEMS, NERVOUS AND ENDOCRIN TO CLINICAL
      MEDICINE.

PMID- 18738566
TI  - MANIFESTATIONS OF LESIONS IN THE POSTERIOR URETHRA.

PMID- 18738568
TI  - BIOLOGICAL FACTS ABOUT BENZYL BENZOATE THERAPY.

PMID- 18738567
TI  - FURTHER STUDIES ON THE NATURE OF FEVER.

PMID- 18738570
TI  - THE 1922 MEETING OF THE STATE SOCIETY.

PMID- 18738569
TI  - THE PSYCHOPATHOLOGY OF SOMATIC DISEASE.

PMID- 18738571
TI  - CARDIAC IRREGULARITIES: Illustration of Normal and Abnormal Mechanism of the
      Heart-Beat by Moving Pictures.

PMID- 18738572
TI  - California Association of Medical Social Workers.

PMID- 18738573
TI  - Association of Radiographers.

PMID- 18738574
TI  - County Societies.

PMID- 18738575
TI  - Deaths.

PMID- 18738576
TI  - FIXING THE SURGEON'S FEE.

PMID- 18738577
TI  - STOCK SELLING HOSPITALS.

PMID- 18738578
TI  - THE CANCER SITUATION.

PMID- 18738579
TI  - ACUTE MECHANICAL OBSTRUCTION OF THE SMALL INTESTINE.

PMID- 18738580
TI  - UNCOMPLICATED FRACTURES OF THE PELVIC RING.

PMID- 18738582
TI  - THE ETIOLOGY OF PARENCHYMATOUS NEPHRITIS.

PMID- 18738581
TI  - THE INCIDENCE AND CLINICAL SIGNIFICANCE OF FLAGELLATE INFECTION IN CERTAIN
      CHRONIC DISEASES.

PMID- 18738583
TI  - CALIFORNIA'S CANCER PROBLEM: Cancer Week, October 30 to November 5.

PMID- 18738585
TI  - THE MOTAIS OPERATION FOR PTOSIS REPORT OF SIX OPERATIONS.

PMID- 18738584
TI  - CHRONIC LESIONS OF THE LOWER LIP.

PMID- 18738586
TI  - NOTES ON PRE-NATAL CARE.

PMID- 18738587
TI  - THE GREAT SECOND TYPE OF CHRONIC ARTHRITIS-FURTHER STUDIES.

PMID- 18738588
TI  - THINGS EVERY PHYSICIAN SHOULD READ.

PMID- 18738589
TI  - THE MODERN METHOD OF FEEDING INFANTS.

PMID- 18738590
TI  - SLEEP REQUIREMENTS OF CHILDREN.

PMID- 18738591
TI  - QUALIFICATIONS FOR MEMBERSHIP.

PMID- 18738592
TI  - County Societies.

PMID- 18738593
TI  - Deaths.

PMID- 18738594
TI  - ABOUT "FEE SPLITTING".

PMID- 18738595
TI  - "EVANGELISTS" OF SORTS.

PMID- 18738596
TI  - AN ANATOMICAL STUDY OF EIGHT CASES OF DEGENERATION OF THE CORNEA.

PMID- 18738597
TI  - MONKEY TESTICLES AND "LOST MANHOOD".

PMID- 18738598
TI  - PUBLIC HEALTH AND MEDICAL WELFARE.

PMID- 18738599
TI  - NEUROLOGICAL FINDINGS IN ONE THOUSAND GROUP STUDY CASES.

PMID- 18738600
TI  - METABOLISM STUDIES IN PULMONARY TUBERCULOSIS.

PMID- 18738601
TI  - THE DIFFERENTIATION OF EARLY MENINGITIS AND MASTOIDITIS.

PMID- 18738602
TI  - THE RATIONALE OF RADIATION IN THE FEMALE PELVIS.

PMID- 18738604
TI  - THE EARLY DIAGNOSIS AND THE TREATMENT OF CANCER OF THE CERVIX.

PMID- 18738603
TI  - INFANTILE ATROPHY: SPECIAL REFERENCE TO FEEDING.

PMID- 18738605
TI  - TREATMENT OF SYPHILIS WITH SILVER-SALVARSAN.

PMID- 18738607
TI  - County Societies.

PMID- 18738606
TI  - THE VALUE OF BLOOD STUDIES.

PMID- 18738609
TI  - Deaths.

PMID- 18738608
TI  - Things Every Physician Should Read.

PMID- 18738610
TI  - Openings in U. S. Public Health Service.

PMID- 18738611
TI  - THE USE OF QUINIDIN IN CARDIAC ARRHYTHMIAS.

PMID- 18738613
TI  - RETURN TO WORK AFTER INJURY.

PMID- 18738612
TI  - ON ADVERTISING IN LAY PUBLICATIONS.

PMID- 18738614
TI  - INSURANCE RATES A GUIDE TO HYGIENIC CONDITIONS SURROUNDING DIFFERENT OCCUPATIONS.

PMID- 18738615
TI  - OCCUPATIONAL DISEASES OF THE SKIN AND HANDS IN CALIFORNIA INDUSTRY.

PMID- 18738616
TI  - THE DEVELOPMENT OF A MODERN MEDICAL SERVICE FOR THE INDUSTRIAL INJURED AND SICK
      AT THE HAHNEMANN HOSPITAL OF THE UNIVERSITY OF CALIFORNIA.

PMID- 18738617
TI  - THE SERVICE OF NEUROPSYCHIATRY TO INDUSTRIAL MEDICINE.

PMID- 18738619
TI  - CLINICAL EXPERIENCE AS TO THE SEVERAL KINDS OF PHYSIOTHERAPY EMPLOYED IN
      RECONSTRUCTION WORK.

PMID- 18738618
TI  - POST-TRAUMATIC NEUROSES: THEIR MECHANISM.

PMID- 18738620
TI  - FRACTURED FEMURS.

PMID- 18738621
TI  - EFFICIENT RECORD MAKING IN THE TREATMENT OF INDUSTRIAL DISABILITIES.

PMID- 18738622
TI  - EXAMINATION OF APPLICANTS FOR LIFE INSURANCE.

PMID- 18738623
TI  - County Societies.

PMID- 18738624
TI  - State Society.

PMID- 18738625
TI  - Department of Pharmacy and Chemistry.

PMID- 18738626
TI  - Deaths.

PMID- 18738627
TI  - The New Year.

PMID- 18738628
TI  - The Physician's Family.

PMID- 18738629
TI  - Missing Link in Our Operative Technique.

PMID- 18738631
TI  - Tic Douloureux.

PMID- 18738630
TI  - Improvement Following Tonsillectomy Clinically Expressed.

PMID- 18738632
TI  - Plastic Surgery in and About the Eyelids.

PMID- 18738633
TI  - Intracranial Hemorrhage of the New-born. Report of a Case.

PMID- 18738634
TI  - Prolapse of the Uterus With Rectocele and Cystocele.

PMID- 18738635
TI  - Ovarian Autotransplantation.

PMID- 18738636
TI  - Chronic Tuberculosis in Early Infancy.

PMID- 18738637
TI  - Nephrectomy in Hunchbacks-With Report of Two Cases.

PMID- 18738639
TI  - State Society-Yosemite Valley.

PMID- 18738638
TI  - Etiology of Gout.

PMID- 18738640
TI  - Department of Pharmacy and Chemistry.

PMID- 18738641
TI  - County Societies.

PMID- 18738642
TI  - Criminal Abortion.

PMID- 18738643
TI  - Correspondence.

PMID- 18738644
TI  - Taxing the Physician.

PMID- 18738645
TI  - Correspondence.

PMID- 18738646
TI  - California Assn. of Medical Social Workers.

PMID- 18738647
TI  - Deaths.

PMID- 18738648
TI  - Extrapleural Thoracoplasty.

PMID- 18738650
TI  - Treatment of Goitre.

PMID- 18738649
TI  - Urinary Pus Cell Count.

PMID- 18738651
TI  - Radium Emanation. A Laboratory and Clinical Study of the Bactericidal Action of
      Solutions of.

PMID- 18738652
TI  - THE OPERATIVE TREATMENT OF STRABISMUS.

PMID- 18738653
TI  - UROLOGICAL DIAGNOSIS.

PMID- 18738654
TI  - TONSILLECTOMY.

PMID- 18738656
TI  - THE SPECIALIST AND HIS OBLIGATION TO THE PROFESSION.

PMID- 18738655
TI  - INADEQUATE PERSONALITY WITH SPECIAL REFERENCE TO ITS INFLUENCE ON BOTH DIAGNOSIS
      AND TREATMENT.

PMID- 18738657
TI  - A REPORT OF THE WORK OF THE RADIUM DEPARTMENT OF THE UNIVERSITY OF CALIFORNIA
      HOSPITAL, BETWEEN APRIL, 1920, AND APRIL, 1921.

PMID- 18738658
TI  - STRICTURE OF THE URETHRA IN WOMEN.

PMID- 18738659
TI  - PRE-ATAXIC GASTRIC CRISES OF TABES.

PMID- 18738660
TI  - GASTROENTEROPTOSIS.

PMID- 18738662
TI  - FALLACY OF THE USUAL TESTS FOR SWIMMING POOLS.

PMID- 18738661
TI  - THE AMOEBA AS THE CAUSE OF THE SECOND GREAT TYPE OF CHRONIC ARTHRITIS:
      PRELIMINARY NOTE.

PMID- 18738664
TI  - A PROBLEM IN MEDICAL ECONOMICS.

PMID- 18738663
TI  - WILL "FOOD SPECIALISTS" SUPERSEDE PHYSICIANS.

PMID- 18738666
TI  - THE ART OF MEDICINE.

PMID- 18738665
TI  - MINERAL WATERS.

PMID- 18738667
TI  - Yosemite's Comfortable Cabins.

PMID- 18738668
TI  - Chaulmoogra Oil Therapy in Leprosy.

PMID- 18738669
TI  - Lane Lectures.

PMID- 18738671
TI  - THE REJUVENATION OF MEDICAL ETHICS.

PMID- 18738670
TI  - NATIONAL BOARD OF MEDICAL EXAMINERS.

PMID- 18738672
TI  - COUNTY SOCIETIES.

PMID- 18738673
TI  - SECTION ON ANESTHESIOLOGY OF THE CALIFORNIA STATE MEDICAL SOCIETY AND THE PACIFIC
      COAST ASSOCIATION OF ANESTHETISTS.

PMID- 18738675
TI  - DEATHS.

PMID- 18738674
TI  - HOSPITALS: SAN FRANCISCO HOSPITAL SURGICAL CLINICS.

PMID- 18738676
TI  - GLUCOSE AND ALKALIES IN SURGERY.

PMID- 18738678
TI  - NON-CANCELLABLE INCOME INSURANCE POLICIES.

PMID- 18738677
TI  - REGARDING GROUP PRACTICE AND PAY CLINICS.

PMID- 18738679
TI  - MEDICAL BOOKS.

PMID- 18738680
TI  - YOSEMITE'S CLIMATE.

PMID- 18738682
TI  - THE ST. LOUIS MEETING OF THE AMERICAN MEDICAL ASSOCIATION.

PMID- 18738681
TI  - CAMP CURRY'S ATTRACTIONS.

PMID- 18738683
TI  - COUNTY SOCIETIES.

PMID- 18738684
TI  - MISCELLANEOUS: ADDITIONS TO EXTENSION LECTURES.

PMID- 18738685
TI  - AN APPRECIATION OF WALTER LINDLEY.

PMID- 18738687
TI  - TREATMENT OF THE LACERATED AND INFECTED CERVIX UTERI.

PMID- 18738686
TI  - DEATHS.

PMID- 18738688
TI  - PRELIMINARY REPORT ON AN INVESTIGATION OF THE "PROVOCATIVE WASSERMANN" CONTROLLED
      BY THE ICE-BOX METHOD.

PMID- 18738689
TI  - OPERABILITY OF THE SENILE PROSTATE-A REMINDER TO THE GENERAL PRACTITIONER.

PMID- 18738690
TI  - DIARRHOEA IN INFANTS IN RELATION TO CERTAIN FOOD INTOLERANCES.

PMID- 18738692
TI  - DETERMINATION OF THE EXTENT AND NATURE OF THE RENAL LESION IN BRIGHT'S DISEASE.

PMID- 18738691
TI  - THE MEANING OF THE PASSAGE OF INTRAPARTUM MECONIUM.

PMID- 18738693
TI  - RECENT ADVANCES IN THE DIAGNOSIS AND TREATMENT OF HAY FEVER AND ASTHMA.

PMID- 18738694
TI  - STYLOID PROCESS IN TONSILLECTOMY.

PMID- 18738695
TI  - WALTER LINDLEY, M. D: Born Monrovia, Indiana, January 13, 1852 Died Los Angeles,
      January 24, 1922.

PMID- 18738697
TI  - THE DIFFERENTIAL DIAGNOSIS OF ECZEMATOID DISEASES.

PMID- 18738696
TI  - SUPRAPUBIC VERSUS PERINEAL PROSTATECTOMY: A COMPARATIVE STUDY OF 134 PERSONAL
      CASES.

PMID- 18738698
TI  - ST. LOUIS MEETING OF THE AMERICAN MEDICAL ASSOCIATION.

PMID- 18738699
TI  - ORAL FOCI OF INFECTION, THEIR DIAGNOSIS, DIFFERENTIATION AND SYSTEMIC
      MANIFESTATIONS.

PMID- 18738701
TI  - UNUSUAL COMPLICATIONS IN A CASE OF MIDDLE EAR INFECTION.

PMID- 18738700
TI  - SOME CLINICAL ASPECTS OF PNEUMONIA.

PMID- 18738702
TI  - THE TREATMENT OF HUNNER'S ULCER OF THE BLADDER BY FULGURATION.

PMID- 18738703
TI  - THE RADICAL MASTOID OPERATION UNDER LOCAL ANAESTHESIA.

PMID- 18738705
TI  - PERSONAL OBSERVATIONS ON UNUSUAL FORMS OF ACUTE POLIOMYELITIC PARALYSIS: With
      Remarks on Clinically Related Types of Epidemic Encephalitis and Landry's
      Paralysis.

PMID- 18738704
TI  - PYELONEPHRITIS: A CRITICAL REVIEW OF 100 CASES.

PMID- 18738706
TI  - STANFORD COLLOQUIA AT THE SAN FRANCISCO HOSPITAL.

PMID- 18738707
TI  - ARE YOU GOING TO ST. LOUIS?